GEMINI SURFACTANTS Field of the Invention

[0001] The present invention relates to surface active agents derived from organic polyhydroxy compounds, more particularly to gemini surfactants derived from organic polyhydroxy compounds. The present invention further relates to the use of these surfactants as cleansing agents or in industry, including in fluid systems utilized in the petroleum industry.

Background of the Invention

[0002] Surfactants, or surface active agents, either dispersed in solution as monomers or as aggregates (e.g., spherical micelles), are used widely in a number of industrial and pharmaceutical processes. In addition, surfactants are used as cleansers, detergents and emulsifying agents and are found in a wide range of personal care and household products such as shampoos, laundry detergents and dishwashing detergents. Surfactants also find use in a variety of fluid and remediation technologies used in the oil-services industry. For example, surfactants are routinely used as wetting agents and emulsifiers in both water based and oil based drilling fluids, and are effective in preventing accretion, the process by which drilled cuttings and the metal tools used in the drilling process often become coated with a gummy, resinous film when wells are drilled through oil sands. [0003] In addition, surfactants are useful in hydraulic fracturing, a process used to treat either depleted wells in later stages of production or wells in reservoirs of low permeability. In this process, the well is treated with a fluid system at a pressure high enough to fracture the formation, which creates new channels permitting the flow of oil and gas to the well bore. In many cases, the fracturing fluid is a polymeric solution of sufficient viscosity to suspend a large quantity of particulate matter (known as the proppant), the purpose of which is to prop open the fractures and maintain the flow pathways after the fluid solution is either removed to the surface or is subsequently lost to the formation. Surfactants forming worm-like micelles are especially useful as a component in fracturing fluids, because of their favourable viscoelastic properties. [0004] Surfactants are also used in stimulation fluids, which are injected into a formation at a distance from the producing well under relatively high pressures to create a driving force to squeeze more oil from the production zone. The surfactants act to reduce the interfacial energy between the near well bore and the producing fluid and to help solubilize waxy materials that often precipitate out in the near well bore area and reduce the permeability of the zone. The selection and use of a suitable surfactant can result in vastly improved recoveries from underground reservoirs. The correlation between the ability to reduce the energy required to create new surfaces and interfaces and the ability to mobilize reservoir entrapped petroleum reserves is described by Schramm et al (Schramm, L.L.; Smith, R. G.; Stone, J.A. Colloids and Surfaces 1984, 11, 247-263).

[0005] Because of their ability to increase the bioavailability of the oil to bacteria in the remediation cycle, surfactants are also used to accelerate bioremediation, or the bacterial removal of oil from cuttings formed during the drilling of oil wells. A critical element in the application of bioremediation technologies is the tendency of surfactant solutions to lower the energy required to create new interfacial area. The ability of the surfactant to lift grease and oil from a solid matrix is directly related to its wetting ability; hence the wetting ability, and the ability of the surfactant to lower surface and interfacial tension, are both key parameters in assessing the utility of surfactants in bioremediation applications. Wetting abilities are closely related to the efficiency with which the surfactant molecules preferentially adsorb at solid surfaces and liquid interfaces.

[0006] The performance of common surfactants in various applications has been investigated (for example, see Detergency of Specialty Surfactants; Marcel Dekker: New York, 2001 ; Vol. 98 and Guyot, A. Adv. Colloid I nterf. Sci. 2004, 708, 3-22). Common conventional surfactants generally contain a single polar or ionic hydrophilic headgroup (e.g., sulfate or carboxylate) covalently bound to a single hydrophobic linear or branched hydrocarbon or fluorocarbon chain. The polar or ionic headgroup interacts strongly with an aqueous environment and is solvated via dipole-dipole or ion-dipole interactions, while the nonpolar hydrophobic chains interact only very weakly with water, resulting in the formation of ordered water molecules in the vicinity of the nonpolar chain, termed the 'hydrophobic effect' (Southall, NT.; Dill, K.A.; Haymet, A.D.J. J. Phys. Chem. B 2002, 106, 521-533). Because of this, surfactant molecules, which are amphiphilic, interacting strongly with both hydrophilic and hydrophobic phases, will tend to adsorb at an air-water interface, thus lowering the surface tension and reducing the Gibbs energy at the air- water interface.

[0007] Surfactants self-assemble at a specific concentration (the critical micelle concentration, or CMC value) into molecular aggregates, known as micelles. If the surfactant is ionic, the self-assembly process is accompanied by the adsorption of counterions at the micellar surface. Generally, ionic surfactants are not fully neutralized at the micellar surface and the self-assembled unit will possess a charge. The number of counterions adsorbed at the micellar surface per number of charged headgroups at the interface is known as the degree of counterion binding (β). β-values for ionic surfactants are typically in the range of 0.4 - 0.7. β-values are determined primarily by conductivity experiments (Jobe, DJ. ; Reinsborough, V.C. Aust. J. Chem. 1984, 37, 303-310), ion- 5 selective electrode experiments (Palepu, R.; Hall, D. G.; Wyn-Jones, E. J. Chem. Soc, Faraday Trans. 1990, 86, 1535-1538), and NMR counterion relaxation rates and chemical shifts (Chachaty, C. Prog. Nucl. Magn. Reson. Spectrosc. 1987, 19, 183-222).

[0008] Micelles are termed association colloids, and are generally thought to be spherical at concentrations slightly above the CMC value (Chang, N.J.; Kaler, E.W. J.

10 Phys. Chem. 1985, 89, 2996-3000). The aggregation number (the number of surfactant molecules per micelle) of common surfactant micelles is generally in the range of about 50-100 monomers, with a radius similar to that of the length of an extended hydrocarbon chain (Gorski, N.; Kalus, J. Langmuir 2001, 17, 4211-4215). The micellar interior, being composed essentially of hydrocarbon chains, has properties closely related to a liquid

15 hydrocarbon (Sόderman, O.; Stubs, P. Prog. Nucl. Magn. Reson. Spectrosc. 1994, 26, 445-482).

[0009] The term "gemini surfactant" has become accepted in the surfactant literature for describing dimeric surfactants (Menger, F.M.; Littau, CA. J. Am. Chem. Soc. 1991, 113, 1451-1452; Zana, R.; Xia, J. Introduction. In Gemini Surfactants: Synthesis,

20 lnterfacial and Solution-phase Behaviour, and Applications, Zana, R., Xia, J., Eds.; Marcel Dekker: New York, 2004; pp 1-8.), that is, surfactant molecules that have two hydrophilic (chiefly ionic) groups and two tails per surfactant molecule. These twin parts of the surfactants are linked by a spacer group of varying length (most commonly a methylene spacer or an oxyethylene spacer). Figure 1 shows a block diagram of a

25 typical gemini surfactant. The term gemini surfactant is also used to describe surfactants with more than two heads and tails.

[0010] Gemini surfactants can have significant advantages over existing single- headed, single-tailed surfactants in a variety of applications because of their advantageous properties (Menger, F.M.; Littau, CA. J. Am. Chem. Soc. 1991, 113,

30 1451-1452; Menger, F.M.; Keiper, J.S. Angew. Chem. Int. Ed. 2000, 39, 1907-1920; Zana, R. Adv. Colloid Interf. Sci. 2002, 97, 205-253; Rosen, MJ. Cosmetics & Toiletries 1998, 113, 49-55). In general, gemini surfactants are more efficient at forming micelles and at adsorbing at the air-water interface than conventional surfactants, resulting in a large reduction in surface tension for a relatively small amount of added gemini

35 surfactant. [0011] Although gemini surfactants have existed since the 1930's, (Rosen, MJ. Chemtech 1993, 23, 30-33) and are commercially available from the Dow Chemical Company as the Dowfax ^® surfactants and from Air Products as the Surfynol ^® surfactants, the surfactants used in the production of fluids for use in oil well drilling or subsequent remediation generally consist of mixtures of single-headed, single-tailed species. Thus there is a need in the oil and gas industry for new surfactants which have the beneficial properties of gemini surfactants.

Summary of the Invention

[0012] The present invention provides novel gemini surfactants which find particular use in industry, including the petroleum industry.

[0013] In one aspect, the present invention provides a compound of formula IA

IA wherein A is a core derived from an organic polyhydroxy compound; R ¹ and R ² are each independently a hydrophobic group; and R ³ and R ⁴ are each independently a surfactant headgroup.

[0014] Another aspect of the present invention provides the use of a compound of formula IA as defined herein as a surfactant.

[0015] Another aspect of the present invention provides a fluid for use in the production or recovery of petroleum from petroleum-bearing formations, the fluid comprising a compound of formula IA as defined herein.

[0016] According to another aspect of the present invention, there is provided a method of using a fluid comprising a compound of formula IA as defined herein in the production or recovery of petroleum from petroleum-bearing formations.

Brief Description of the Drawings [0017] Specific embodiments of the present invention are now described in greater detail and can be better understood by the skilled person when read in conjunction with the drawings in which:

[0018] Figure 1 is a block diagram of a typical gemini surfactant; [0019] Figure 2 is a plot of surface tension (mN-rn ^'1 ) versus log ₁₀ of the total surfactant concentration (molar) for Compounds 5a-5d (Examples 5A-5D); and

[0020] Figure 3 is a plot of surface tension (mN m ¹ ) versus log ₁₀ of the total surfactant concentration (molar) for compounds 22c-22f (Examples 22C-22F). Definitions

[0021] The term "substituent", as used herein and unless specified otherwise, is intended to mean an atom, radical or group which may be bonded to a carbon atom, a heteroatom or any other atom which may form part of a molecule or fragment thereof, which would otherwise be bonded to at least one hydrogen atom. Substituents contemplated in the context of a specific molecule or fragment thereof are those which give rise to chemically stable compounds, such as are recognized by those skilled in the art.

[0022] The terms "alkyl" or "(Ci- _n )alkyl" as used herein and unless specified otherwise, wherein n is an integer, either alone or in combination with another radical, are intended to mean an acyclic or cyclic, straight or branched chain, saturated or unsaturated alkyl radical containing from 1 to n carbon atoms. "Alkyl" includes, but is not limited to, methyl, ethyl, propyl (n-propyl), butyl (n-butyl), 1-methylethyl (iso-propyl), 1-methylpropyl (sec- butyl), 2-methylpropyl (iso-butyl), 1 ,1-dimethylethyl (tert-butyl), pentyl (n-pentyl), hexyl (n-hexyl), octyl (n-octyl), decyl (n-decyl), dodecyl (n-dodecyl), and tetradecyl (n-tetradecyl). The abbreviation Me denotes a methyl group; Et denotes an ethyl group, Pr denotes a propyl group, iPr denotes a 1-methylethyl group, Bu denotes a butyl group and tBu denotes a 1 ,1-dimethylethyl group. Unsaturated alkyl groups include alkenyl and alkynyl groups. Cyclic alkyl groups include cycloalkyl groups.

[0023] The terms "alkenyl" or "(C ₂ - _n )alkenyl", as used herein and unless specified otherwise, wherein n is an integer, either alone or in combination with another radical, are intended to mean an unsaturated, acyclic straight or branched chain radical containing two to n carbon atoms, at least two of which are bonded to each other by a double bond. Examples of such radicals include, but are not limited to, ethenyl (vinyl), 1-propenyl, 2-propenyl, and 1-butenyl. Unless specified otherwise, the term "(C ₂ - _n )alkenyl" is understood to encompass individual stereoisomers where possible, including but not limited to (E) and (Z) isomers, and mixtures thereof. When a (C ₂ - _π )alkenyl group is substituted, it is understood to be substituted on any carbon atom thereof which would otherwise bear a hydrogen atom, unless specified otherwise, such that the substitution would give rise to a chemically stable compound. [0024] The terms "alkynyl" or "(C ₂ - _n )alkynyl", as used herein and unless specified otherwise, wherein n is an integer, either alone or in combination with another radical, are intended to mean an unsaturated, acyclic straight or branched chain radical containing two to n carbon atoms, at least two of which are bonded to each other by a triple bond. Examples of such radicals include, but are not limited to, ethynyl, 1-propynyl, 2-propynyl, and 1-butynyl. When a (C ₂ . _n )alkynyl group is substituted, it is understood to be substituted on any carbon atom thereof which would otherwise bear a hydrogen atom, unless specified otherwise, such that the substitution would give rise to a chemically stable compound.

[0025] The terms "cycloalkyl" or "(C ₃ . _m )cycloalkyl" as used herein and unless specified otherwise, wherein m is an integer, either alone or in combination with another radical, are intended to mean a saturated or unsaturated cycloalkyl substituent containing from 3 to m carbon atoms and includes, but is not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl and cycloheptyl.

[0026] The terms "alkoxy" or "(Ci. _n )alkoxy" as used herein and unless specified otherwise, wherein n is an integer, either alone or in combination with another radical, are intended to mean an oxygen atom further bonded to a saturated alkyl group containing 1 to n carbon atoms as defined above. "Alkoxy" includes, but is not limited to, methoxy (-OCH ₃ ), ethoxy (-OCH ₂ CH ₃ ), propoxy (-OCH ₂ CH ₂ CH ₃ ), butoxy (-OCH ₂ CH ₂ CH ₂ CH ₃ ), 1-methylethoxy (-OCH(CHa) ₂ ), and 1 ,1-dimethylethoxy (-OC(CH ₃ ) ₃ ). [0027] The term "aryl" as used herein and unless specified otherwise, either alone or in combination with another radical, is intended to mean a carbocyclic aromatic monocyclic group containing 6 carbon atoms which may be further fused to a second 5- or 6- membered carbocyclic group which may be aromatic, saturated or unsaturated. "Aryl" includes, but is not limited to, phenyl, indanyl, indenyl, 1-naphthyl, 2-naphthyl, tetrahydronaphthyl and dihydronaphthyl.

[0028] The terms "arylalkyl" or "aryl(Ci _-n )alkyr as used herein and unless specified otherwise, wherein n is an integer, either alone or in combination with another radical, are intended to mean a saturated, acyclic alkyl radical having 1 to n carbon atoms as defined above which is itself substituted with an aryl radical as defined above. Examples of arylalkyl include, but are not limited to, phenylmethyl (benzyl), 1-phenylethyl,

2-phenylethyl and phenylpropyl. When an arylalkyl group is substituted, it is understood that substituents may be attached to either the aryl or the alkyl portion thereof or both, unless specified otherwise, such that the substitution would give rise to a chemically stable compound, such as are recognized by those skilled in the art. [0029] The term "heteroatom" as used herein and unless specified otherwise is intended to mean 0, S or N.

[0030] The term "carbocycle" as used herein and unless specified otherwise, either alone or in combination with another radical, is intended to mean a 3- to 8-membered saturated, unsaturated or aromatic cyclic radical in which all of the ring members are carbon atoms, and which may be fused to one or more 3- to 8-membered saturated, unsaturated or aromatic carbocyclic groups. When a carbocycle is substituted, it is understood that substituents may be attached to any carbon atom which would otherwise bear a hydrogen atom, unless specified otherwise, such that the substitution would give rise to a chemically stable compound, such as are recognized by those skilled in the art. [0031] The term "heterocycle" as used herein and unless specified otherwise, either alone or in combination with another radical, is intended to mean a 4- to 10-membered saturated, unsaturated or aromatic monocyclic heterocycle containing from 1 to 4 heteroatoms each independently selected from O, N and S which is optionally fused to one or more other cycle, including a carbocycle, a heterocycle or any other cycle; or a monovalent radical derived by removal of a hydrogen atom therefrom. Examples of such heterocycles include, but are not limited to, azetidine, pyrrolidine, tetrahydrofuran, tetrahydrothiophene, thiazolidine, oxazolidine, pyrrole, thiophene, furan, pyrazole, imidazole, isoxazole, oxazole, isothiazole, thiazole, triazole, tetrazole, piperidine, piperazine, azepine, diazepine, pyran, 1 ,4-dioxane, 4-morpholine, 4-thiomorpholine, pyridine, pyridine-N-oxide, pyridazine, pyrazine, pyrimidine, indole, isoindole, benzimidazole, benzothiophene, benzofuran, benzopyran, benzodioxole, benzodioxane, benzothiazole, quinoline, isoquinoline, and naphthyridine, and saturated, unsaturated and aromatic derivatives thereof.

[0032] The term "polyoxyalkylene" as used herein and unless specified otherwise, either alone or in combination with another radical, is intended to mean a radical of the formula -(O-(C(R ^a )(R ^b )) _n ) _m -, wherein n is an integer from 1 to 6, m is an integer from 1 to 30, and R ^a and R ^b are each independently in each instance selected from H and saturated (C _1-6 )alkyl. In at least one embodiment, n is an integer from 1 to 3. In at least one embodiment, n is 2. Examples of polyoxyalkylene include but are not limited to polyoxyethylene, wherein n is 2 and R ^a and R ^b are each H, and polyoxypropylene, wherein n is 2, one instance of R ^a is a methyl group, and R ^b and the other instance of R ^a are each H. In at least one embodiment, when polyoxyalkylene is polyoxyethylene, m is an integer from 1 to 30. In at least one embodiment, when polyoxyalkylene is polyoxypropylene, m is an integer from 1 to 10. As used herein, the term "hydroxyalkylpolyoxyalkylene" is intended to mean a radical of the formula HO-(C(R ^a )(R ^b )) _π -(O-(C(R ^a )(R ^b )) _n ) _m -, wherein n is an integer from 1 to 6, m is an integer from 1 to 30, and R ^a and R ^b are each independently in each instance selected from H and saturated (C _1-6 )alkyl.

[0033] The term "surfactant headgroup" as used herein and unless specified otherwise is intended to mean a polar or ionic hydrophilic group which interacts strongly with water and which is solvated via dipole-dipole or ion-dipole interactions. Examples of surfactant headgroups include but are not limited to hydroxy, sulfonate, sulfate, carboxylate, phosphonate, phosphate, and primary, secondary, tertiary or quaternary ammonium. It will be clear to the skilled person that when a surfactant headgroup is a charged group, a suitable counterion will also be present. When the surfactant headgroup is an anionic group, suitable counterions are cations, including but not limited to metal cations and optionally substituted ammonium cations. When the surfactant headgroup is a cationic group, suitable counterions are anions, including but not limited to halide, hydroxide, nitrate, sulfate, sulfonate, carbonate, carboxylate, phosphate and phosphonate anions. The surfactant headgroup can also include a linker which connects the polar or ionic group to the remainder of the surfactant molecule. Such linkers can have from 1 to 10 atoms each independently selected from C, O, N and S, in addition to any attached hydrogen atoms.

[0034] The term "hydrophobic group" as used herein and unless specified otherwise is intended to mean a group which is hydrophobic or non-polar and which interacts only very weakly with water, or is a polyoxyalkylene or hydroxypolyoxyalkylene group. Examples of hydrophobic groups include but are not limited to alkyl, aryl, arylalkyl, polyoxyalkylene and hydroxypolyoxyalkylene groups, including but not limited to alkyl, aryl, arylalkyl, polyoxyalkylene and hydroxypolyoxyalkylene groups which are unsubstituted or are substituted with non-polar substituents.

Detailed Description of the Invention

[0035] One aspect of the present invention provides a compound of formula IA

IA

wherein A is a core derived from an organic polyhydroxy compound; R ¹ and R ² are each independently a hydrophobic group, and

R ³ and R ⁴ are each independently a surfactant headgroup

[0036] In the following embodiments, groups and substituents of the compounds of formula IA according to the invention are described in detail A

[0037] Core A can be a core derived from any organic compound containing at least two hydroxy groups. Suitable organic compounds include but are not limited to polyalcohols, including but not limited to diols, triols, including but not limited to glycerol, tetraols, including but not limited to pentaerythπtol, and polyols, including but not limited to polyglycerols and polypentaerythntols, sugars, and sugar derivatives, including but not limited to sugar alcohols, sugar acids, alkyl glycosides, oligosaccharides and polysaccharides In at least one embodiment, core A is derived from methyl glucoside, a polyglycerol or pentaerythritol

[0038] In at least one embodiment, wherein A is a core derived from pentaerythritol, the present invention provides a compound of formula I

R ¹ O OR

wherein R ¹ and R ² are each independently a hydrophobic group; and

R ³ and R ⁴ are each independently a surfactant headgroup R ¹ and R ² [0039] In at least one embodiment, R ¹ is identical to R ²

[0040] In at least one embodiment, R ¹ and R ² are each independently a hydrophobic group selected from (C _1-24 )SlRyI, aryl(C _1-2 4)alRyl and (C _1-2 o)hydroxyalkylpolyoxyalkylene; wherein the aryl(C _1-24 )alkyl is optionally substituted with from one to three (Ci. ₂₄ )alkyl groups, and wherein the (C _1-24 )alkyl is optionally substituted with hydroxyl, (Ci. ₂₄ )alkoxy, (C ₁ . ₂₄ )alkyl-C(=O)NH-, or (C ₁ . ₂₄ )alkyl-NHC(=O)-

[0041] In at least one embodiment, R ¹ and R ² are each independently selected from (Ci _-24 )alkyl, aryl(C ₁ . ₂₄ )alkyl and (C _{1 14} )hydroxyalkylpolyoxyalkylene, wherein the (C _1-24 )alkyl is optionally substituted with hydroxyl and the aryl(C ₁ . ₂₄ )alkyl is optionally substituted with (C _1-24 )alkyl [0042] In at least one embodiment, R ¹ and R ² are each independently selected from (C _8- i ₄ )alkyl, aryl(d-e)alkyl substituted with (C _8-12 )alkyl, and (C _1-6 )alkyl substituted with hydroxyl.

[0043] In at least one embodiment, at least one of R ¹ and R ² is (d^alkyl. [0044] In at least one embodiment, at least one of R ¹ and R ² is (C _B- i ₄ )alkyl.

[0045] In at least one embodiment, at least one of R ¹ and R ² is selected from octyl, nonyl, decyl, undecyl, dodecyl, tridecyl and tetradecyl.

[0046] In at least one embodiment, at least one of R ¹ and R ² is aryl(C _1-6 )alkyl substituted with (C ₈ .i ₂ )alkyl. [0047] In at least one embodiment, at least one of R ¹ and R ² is phenyl-CH ₂ - substituted with (C ₈ .i ₂ )alkyl.

[0048] In at least one embodiment, at least one of R ¹ and R ² is phenyl-CH ₂ - substituted with a group selected from octyl, nonyl, decyl, undecyl and dodecyl.

[0049] In at least one embodiment, at least one of R ¹ and R ² is (C _1-6 )alkyl substituted with hydroxyl.

[0050] In at least one embodiment, at least one of R ¹ and R ² is selected from hydroxyethyl and hydroxypropyl.

R ³ and R ⁴

[0051] In at least one embodiment, R ³ is identical to R ⁴ . [0052] In at least one embodiment, R ³ and R ⁴ are each independently a surfactant headgroup selected from -OH, -SO ₃ ^" , -(d-e)alkyl-SO ₃ -, -O(C _1-6 )alkyl-SO ₃ ^' , -OSO ₃ ^" , -(d- ₆ )alkyl-OSO ₃ \ -O(C ₂ . ₆ )alkyl-OSO ₃ \ -COO ^" , -(C^alkyl-COO ^" , -O(d-β)alkyl-COO\ -PO ₃ ² -, -(C _1-6 )alkyl-PO ₃ ^2' , -O(d- ₆ )alkyl-PO ₃ ² -, -PO ₃ H ^" , -(d. ₆ )alkyl-PO ₃ H\ -O(d. ₆ )alkyl-PO ₃ H-, -OPO ₃ ² -, -(d. ₆ )alkyl-OPO ₃ ² \ -O(C ₂ . ₆ )alkyl-OPO ₃ ^2" , -OPO ₃ H-, -(d. ₆ )alkyl-OPO ₃ H-, -OCC^alkyl-OPOsH ^' , -N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ , -(d. ₆ )alkyl-N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ , and -O(C _2-6 )alkyl-N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ ; wherein R ⁵ , R ⁶ and R ⁷ are each independently in each instance H, -(d-e)alkyl, -(C ₂ . ₆ )alkyl-OH, -(d^alkyl-SO/, -(C ₂ ^)alkyl-OSO ₃ -, -(C _1-6 )alkyl-PO ₃ H-, -(C ₂ . ₆ )alkyl-OPO ₃ H- , -(d-eJalkyl-COO ^" , or at least two of R ⁵ , R ⁶ and R ⁷ are joined, together with the N atom to which they are attached, to form a heterocycle containing one N heteroatom and optionally from 1 to 3 further heteroatoms each independently selected from N, O and S, the heterocycle being optionally substituted with from one to three substituents each independently selected from (d _-6 )alkyl and aryl. [0053] It will be clear to the skilled person that when R ³ or R ⁴ is a charged group, a suitable counterion will also be present. When at least one of R ³ and R ⁴ is an anionic group, suitable counterions are cations, including but not limited to metal cations and optionally substituted ammonium cations. When at least one of R ³ and R ⁴ is a cationic group, suitable counterions are anions, including but not limited to halide, hydroxide, nitrate, sulfate, sulfonate, carbonate, carboxylate, phosphate and phosphonate anions. It is also contemplated that one of R ³ and R ⁴ can be an anionic group and the other of R ³ and R ⁴ can be a cationic group, such that a zwitterionic or amphoteric structure results and further counterions are not necessary. Alternatively, at least one of R ³ and R ⁴ can contain both an anionic group and a cationic group, such that the at least one of R ³ and R ⁴ is itself zwitterionic.

[0054] In at least one embodiment, at least one of R ³ and R ⁴ is an anionic surfactant headgroup selected from -SO ₃ ^" , -(C ₁ . ₆ )alkyl-SO ₃ ^' _I -O(d. ₆ )alkyl-SO ₃ ^" , -OSO ₃ ^' , -(d- ₆ )alkyl-OSO ₃ ^" , -O(C ₂ . ₆ )alkyl-OSO ₃ ^" , -COO ^' , -(d. ₆ )alkyl-COO ^" , -O(C _1-6 )alkyl-COO ^" , -PO ₃ ^2" , -(C ₁ . ₆ )alkyl-PO ₃ ² -, -O(C _1-6 )alkyl-PO ₃ ^2" , -PO ₃ H ^" , -(C _1-6 )alkyl-PO ₃ H ^" ,

-O(C _1-6 )alkyl-PO ₃ H-, -OPO ₃ ^2" , -(C ₁ . ₆ )alkyl-OPO ₃ ² -, -O(C ₂ . ₆ )alkyl-OPO ₃ ^2" , -OPO ₃ H ^" , -(C _1-β )alkyl-OPO ₃ H ^" and -O(C ₂ . ₆ )alkyl-OPO ₃ H\

[0055] In at least one embodiment, at least one of R ³ and R ⁴ is an anionic surfactant headgroup selected from -SO ₃ ^" , -(d. ₃ )alkyl-SO ₃ ^" , -O(d _-3 )alkyl-SO ₃ ^" , -OSO ₃ ^" , -(d _-3 )alkyl-OSO ₃ -, -O(C _2-3 )alkyl-OSO ₃ ^' , -OPO ₃ ^2" , -(d. ₃ )alkyl-OPO ₃ ^2' , -O(C ₂ . ₃ )alkyl-OPO ₃ ^2' , -COO ^" , -(d. ₃ )alkyl-COO ^" , and -O(d. ₃ )alkyl-COO ^" .

[0056] In at least one embodiment, at least one of R ³ and R ⁴ is an anionic surfactant headgroup selected from -OSO ₃ ^" , -OCH ₂ CH ₂ OSO ₃ ^" , -OCH ₂ CH ₂ CH ₂ OSO ₃ ^' , -OPO ₃ ^2' , -OCH ₂ CH ₂ OPO ₃ ^2" , -OCH ₂ CH ₂ CH ₂ OPO ₃ ^2" , -COO ^' , -OCH ₂ COO ^" , -OCH ₂ CH ₂ COO ^" , -OCH ₂ CH ₂ CH ₂ COO ^" , -OCH ₂ CH ₂ SO ₃ ^" and -OCH ₂ CH ₂ CH ₂ SO ₃ ^" .

[0057] In at least one embodiment, at least one of R ³ and R ⁴ is a cationic surfactant headgroup selected from -N(R ⁵ )(R ^δ )(R ⁷ ) ⁺ , -(d. ₆ )alkyl-N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ , and -O(C ₂ . ₆ )alkyl-N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ ; wherein R ⁵ , R ⁶ and R ⁷ are each independently in each instance H, -(d. ₆ )alkyl, -(C ₂ . ₆ )alkyl-OH, or at least two of R ⁵ , R ⁶ and R ⁷ are joined, together with the N atom to which they are attached, to form a heterocycle containing one N heteroatom and optionally from 1 to 3 further heteroatoms each independently selected from N, O and S, the heterocycle being optionally substituted with from one to three substituents each independently selected from (d. ₆ )alkyl and aryl. [0058] In at least one embodiment, at least one of R ³ and R ⁴ is a cationic surfactant headgroup selected from -N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ , -(C ₁ . ₆ )alkyl-N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ , and -O(C ₂ . ₆ )alkyl-N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ ; wherein R ⁵ , R ⁶ and R ⁷ are each independently in each instance -(C _1-6 )alkyl,

-(C ₂ - ₆ )alkyl-OH, or at least two of R ⁵ , R ⁶ and R ⁷ are joined, together with the N atom to which they are attached, to form a heterocycle containing one N heteroatom and optionally from 1 to 3 further heteroatoms each independently selected from N, O and S, the heterocycle being optionally substituted with from one to three substituents each independently selected from (Ci-6)alkyl and aryl.

[0059] In at least one embodiment, at least one of R ³ and R ⁴ is a cationic surfactant headgroup selected from -N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ , -(C _1-6 )alkyl-N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ , and -O(C ₂ . ₆ )alkyl-N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ ; wherein R ⁵ , R ⁶ and R ⁷ are each independently in each instance -(Ci _-6 )alkyl,

-(C ₂ - ₆ )alkyl-OH, or two of R ⁵ , R ⁶ and R ⁷ are joined, together with the N atom to which they are attached, to form a A-, 5-, 6-, 7- or 8-membered heterocycle containing one N heteroatom and optionally from 1 to 3 further heteroatoms each independently selected from N, O and S, the heterocycle being optionally substituted with from one to three substituents each independently selected from (C^ _f Oalkyl and aryl.

[0060] In at least one embodiment, at least one of R ³ and R ⁴ is a cationic surfactant headgroup selected from -N(R ⁵ )(R ⁶ )(R ⁷ )\ -(C _1-6 )alkyl-N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ , and -O(C ₂ . ₆ )alkyl-N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ ; wherein R ⁵ , R ⁶ and R ⁷ are each independently in each instance -(Ci. ₆ )alkyl,

-(C ₂ . ₆ )alkyl-OH, or two of R ⁵ , R ⁶ and R ⁷ are joined, together with the N atom to which they are attached, to form a 5- or 6-membered heterocycle containing one N heteroatom, the heterocycle being optionally substituted with from one to three substituents each independently selected from (C _1-6 )alkyl and aryl.

[0061] In at least one embodiment, at least one of R ³ and R ⁴ is a cationic surfactant headgroup selected from -NH ₃ ⁺ (ammonium) Λ/-methylammonium, Λ/,Λ/-dimethylammonium, Λ/,Λ/,Λ/-trimethylammonium, /V-ethylammonium, Λ/,Λ/-diethylammonium, Λ/,Λ/,Λ/-triethylammonium, Λ/,Λ/,Λ/-ethyldimethylammonium, Λ/,Λ/,Λ/-diethylmethylammonium, Λ/-(2-hydroxyethyl)ammonium, Λ/,Λ/-di-(2-hydroxyethyl)ammonium, N,N,N-tri-(2-hydroxyethyl)ammonium, ammoniomethyl, Λ/-methylammoniomethyl, Λ/,Λ/-dimethylammoniomethyl, Λ/,/V,Λ/-trimethylammoniomethyl, Λ/-ethylammoniomethyl, Λ/,Λ/-diethylammoniomethyl, Λ/,Λ/,Λ/-triethylammoniomethyl, Λ/,Λ/,Λ/-ethyldimethylammoniomethyl, Λ/,Λ/,Λ/-diethylmethylammoniomethyl, Λ/-(2-hydroxyethyl)ammoniomethyl, Λ/,Λ/-di(2-hydroxyethyl)ammoniomethyl, Λ/,Λ/,Λ/-tri-(2-hydroxyethyl)ammoniomethyl, 2-ammonioethoxy, 2-(Λ/-methylammonio)ethoxy, 2-(Λ/,Λ/-dimethylammonio)ethoxy, 2-(Λ/,Λ/,Λ/-trimethylammonio)ethoxy, 2-(Λ/-ethylammonio)ethoxy, 2-(Λ/,Λ/-diethylammonio)ethoxy, 2-(Λ/,Λ/,Λ/-triethylammonio)ethoxy,

2-(Λ/,Λ/,Λ/-ethyldimethylammonio)ethoxy, 2-(Λ/,Λ/,Λ/-diethylmethylammonio)ethoxy, 2-{Λ/-(2-hydroxyethyl)ammonio}ethoxy, 2-{Λ/,Λ/-di(2-hydroxyethyl)ammonio}ethoxy, 2-{Λ/,Λ/,Λ/-tri-(2-hydroxyethyl)ammonio}ethoxy, 3-ammoniopropanoxy, 3-(Λ/-methylammonio)propanoxy, 3-(Λ/,Λ/-dimethylammonio)propanoxy, 3-(Λ/,Λ/,Λ/-trimethylammonio)propanoxy, 3-(Λ/-ethylammonio)propanoxy, 3-(Λ/,Λ/-diethylammonio)propanoxy, 3-(Λ/,Λ/,Λ/-triethylammonio)propanoxy, 3-(Λ/,Λ/,Λ/-ethyldimethylammonio)propanoxy, 3-(Λ/,Λ/,Λ/-diethylmethylammonio)propanoxy, 2-{Λ/-(2-hydroxyethyl)ammonio}propanoxy, 3-{Λ/,Λ/-di(2-hydroxyethyl)ammonio}pro- panoxy and 3-{Λ/,Λ/,Λ/-tri-(2-hydroxyethyl)ammonio}propanoxy. [0062] In at least one embodiment, at least one of R ³ and R ⁴ is a zwitterionic surfactant headgroup selected from -N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ , and -O(C ₂ . ₆ )alkyl-N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ ; wherein one of R ⁵ , R ⁶ and R ⁷ is -(d^alkyl-SCV, -(C _2-6 )alkyl-OSO ₃ ^" , -(C _1-6 )alkyl-PO ₃ H ^' , -(C ₂ - ₆ )alkyl-OPO ₃ H ^" or -(C.,. ₆ )alkyl-COO ^" and the remaining two of R ⁵ , R ⁶ and R ⁷ are each independently in each instance H, -(d. ₆ )alkyl, -(C ₂ - ₆ )alkyl-OH, or the remaining two of R ⁵ , R ⁶ and R ⁷ are joined, together with the N atom to which they are attached, to form a heterocycle containing one N heteroatom and optionally from 1 to 3 further heteroatoms each independently selected from N, O and S, the heterocycle being optionally substituted with from one to three substituents each independently selected from (d^alkyl and aryl.

[0063] In at least one embodiment, at least one of R ³ and R ⁴ is a zwitterionic surfactant headgroup selected from -N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ , -(C _1-6 )alkyl-N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ , and -O(C _2-6 )alkyl-N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ ; wherein one of R ⁵ , R ⁶ and R ⁷ is -(C^alkyl-SCV, -(C ₂ . ₆ )alkyl-OSO ₃ ^" , -(C^alkyl-POaH ^" , -(C ₂ . ₆ )alkyl-OPO ₃ H ^~ or -(Ci. ₆ )alkyl-COO ^" and the remaining two of R ⁵ , R ⁶ and R ⁷ are each independently in each instance -(C _1-6 )alkyl, -(C _2-6 )alkyl-OH, or the remaining two of R ⁵ , R ⁶ and R ⁷ are joined, together with the N atom to which they are attached, to form a heterocycle containing one N heteroatom and optionally from 1 to 3 further heteroatoms each independently selected from N, O and S, the heterocycle being optionally substituted with from one to three substituents each independently selected from (C _1-6 )alkyl and aryl.

[0064] In at least one embodiment, at least one of R ³ and R ⁴ is a zwitterionic surfactant headgroup selected from -N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ , -(C _1-6 )alkyl-N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ , and -O(C _2-6 )alkyl-N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ ; wherein one of R ⁵ , R ⁶ and R ⁷ is -(Ci. ₆ )alkyl-SO ₃ ^" , -(C ₂ - ₆ )alkyl-OSO ₃ ^" , -(Ci _-6 )alkyl-PO ₃ H ^" , -(C ₂ - ₆ )alkyl-OPO ₃ H ^" or -(C^alkyl-COO ^" and the remaining two of R ⁵ , R ⁶ and R ⁷ are each independently in each instance -(C _1-6 )alkyl, -(C ₂ . ₆ )alkyl-OH, or the remaining two of R ⁵ , R ⁶ and R ⁷ are joined, together with the N atom to which they are attached, to form a A-, 5-, 6-, 7- or 8-membered heterocycle containing one N heteroatom and optionally from 1 to 3 further heteroatoms each independently selected from N, O and S, the heterocycle being optionally substituted with from one to three substituents each independently selected from (Ci. ₆ )alkyl and aryl.

[0065] In at least one embodiment, at least one of R ³ and R ⁴ is a zwitterionic surfactant headgroup selected from -N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ , -(C ₁ ^)alkyl-N(R ⁵ )(R ^β )(R ⁷ ) ^* , and -O(C _2-6 )alkyl-N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ ; wherein one of R ⁵ , R ⁶ and R ⁷ is -(C _1-6 )alkyl-SO ₃ ^" , -(C _2-6 )alkyl-OSO ₃ ^' , -(Ci _-6 )alkyl-PO ₃ H ^" , -(C ₂ . ₆ )alkyl-OPO ₃ H ^" or -(C _1-6 )alkyl-COO ^" and the remaining two of R ⁵ , R ⁶ and R ⁷ are each independently in each instance -(C _1-6 )alkyl, -(C ₂ . ₆ )alkyl-OH, or the remaining two of R ⁵ , R ⁶ and R ⁷ are joined, together with the N atom to which they are attached, to form a 5- or 6-membered heterocycle containing one N heteroatom, the heterocycle being optionally substituted with from one to three substituents each independently selected from (C^alkyl and aryl.

[0066] In at least one embodiment, at least one of R ³ and R ⁴ is a zwitterionic surfactant headgroup selected from -N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ , -(C ₁ . ₆ )alkyl-N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ , and -O(C ₂ . ₆ )alkyl-N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ ; wherein one of R ⁵ , R ⁶ and R ⁷ is -(C^alkyl-COO ^' and the remaining two of R ⁵ , R ⁶ and R ⁷ are each independently in each instance H, -(C ₁ . ₆ )alkyl, -(C ₂ . ₆ )alkyl-OH, or the remaining two of R ⁵ , R ⁶ and R ⁷ are joined, together with the N atom to which they are attached, to form a heterocycle containing one N heteroatom and optionally from 1 to 3 further heteroatoms each independently selected from N, O and S, the heterocycle being optionally substituted with from one to three substituents each independently selected from (C _1-6 )alkyl and aryl.

[0067] In at least one embodiment, at least one of R ³ and R ⁴ is a zwitterionic surfactant headgroup selected from -N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ , -(C _1-6 )alkyl-N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ , and -O(C _2-6 )alkyl-N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ ; wherein one of R ⁵ , R ⁶ and R ⁷ is -(C^alkyl-COO ^" and the remaining two of R ⁵ , R ⁶ and R ⁷ are each independently in each instance -(C _1-6 )alkyl, -(C ₂ -6)alkyl-OH, or the remaining two of R ⁵ , R ⁶ and R ⁷ are joined, together with the N atom to which they are attached, to form a heterocycle containing one N heteroatom and optionally from 1 to 3 further heteroatoms each independently selected from N, O and S, the heterocycle being optionally substituted with from one to three substituents each independently selected from (C-|. ₆ )alkyl and aryl.

[0068] In at least one embodiment, at least one of R ³ and R ⁴ is a zwitterionic surfactant headgroup selected from -N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ , -(Ci-β)alkyl-N(R ⁵ )(R ^β )(R ⁷ ) ⁺ , and -O(C ₂ . ₆ )alkyl-N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ ; wherein one of R ⁵ , R ⁶ and R ⁷ is -(C ₁ . ₆ )alkyl-COO ^" and the remaining two of R ⁵ , R ⁶ and R ⁷ are each independently in each instance -(C _1-6 )alkyl, -(C _2-6 )alkyl-OH, or the remaining two of R ⁵ , R ⁶ and R ⁷ are joined, together with the N atom to which they are attached, to form a A-, 5-, 6-, 7- or 8-membered heterocycle containing one N heteroatom and optionally from 1 to 3 further heteroatoms each independently selected from N, O and S, the heterocycle being optionally substituted with from one to three substituents each independently selected from (C _1-6 )alkyl and aryl.

[0069] In at least one embodiment, at least one of R ³ and R ⁴ is a zwitterionic surfactant headgroup selected from -N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ , -(Ci _-6 )alkyl-N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ , and -O(C ₂ . ₆ )alkyl-N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ ; wherein one of R ⁵ , R ⁶ and R ⁷ is -(C^alkyl-COO ^" and the remaining two of R ⁵ , R ⁶ and R ⁷ are each independently in each instance -(C _1-6 )alkyl, -(C _2-6 )alkyl-OH, or the remaining two of R ⁵ , R ⁶ and R ⁷ are joined, together with the N atom to which they are attached, to form a 5- or 6-membered heterocycle containing one N heteroatom, the heterocycle being optionally substituted with from one to three substituents each independently selected from (C^alkyl and aryl.

[0070] In at least one embodiment, at least one of R ³ and R ⁴ is a zwitterionic surfactant headgroup selected from Λ/-carboxymethylammonium, Λ/,Λ/-carboxymethylmethylammonium, /VJV./V-carboxymethyldimethylammonium, Λ/-carboxymethylammoniomethyl, /V./V-carboxymethylmethylamrnoniomethyl,

/V,Λ/,Λ/-carboxymethyldimethylammoniomethyl, 2-(Λ/-carboxymethylammonio)ethoxy, 2-(Λ/,Λ/-carboxymethylmethylammonio)ethoxy, 2-(Λ/,Λ/,Λ/-carboxymethyldimethyl- ammonio)ethoxy, 3-(Λ/-carboxymethylammonio)propanoxy, 3-(Λ/,Λ/-carboxymeth- ylmethylammonio)propanoxy, and 3-(Λ/,Λ/,Λ/-carboxymethyldimethylammonio)propanoxy. [0071] In at least one embodiment, the present invention provides a compound of formula I

wherein R ¹ and R ² are each independently a hydrophobic group selected from

(Ci- ₂₄ )alkyl, aryl(Ci. ₂₄ )alkyl and (C _1-20 ) hydroxyalkylpolyoxyalkylene, wherein the aryl(Ci. ₂₀ )alkyl is optionally substituted with from one to three (C _1-24 )alkyl groups, and wherein the (C^alkyl is optionally substituted with hydroxyl, (C^alkoxy, (C ₁ . ₂₄ )alkyl-C(=O)NH-, or (C^alkyl-NHC^O)-, and

R ³ and R ⁴ are each independently a surfactant headgroup selected from -OH, -SO ₃ ^" , -(Ci. ₆ )alkyl-SO ₃ -, -Otd^alkyl-SOs ^" , -OSO ₃ ^" , -(C _1-6 )alkyl-OSO ₃ ^" , -O(C ₂ . ₆ )alkyl-OSO ₃ , -COO ^" , -(C^alkyl-COO ^" , -OCd^alkyl-COO ^" , -PO ₃ ^2" ,

-(C _{1 6} )alkyl-PO ₃ ^2" , -O(C _1-6 )alkyl-PO ₃ ² , -PO ₃ H , -(C^alkyl-POaH ^" , -0{C,. ₆ )a\ky\-P0 _z H , -OPO ₃ ² , -(C _1-6 )alkyl-OPO ₃ ² -, -O(C _2-6 )alkyl-OPO ₃ ² -, -OPO ₃ H ^" , -(d^alkyl-OPOsH , -O(C ₂ . ₆ )alkyl-OPO ₃ H ^" , -N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ , -(C ₁ . ₆ )alkyl-N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ , and -O(C ₂ . ₆ )alkyl-N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ , wherein R ⁵ , R ⁶ and R ⁷ are each independently in each instance H, -(Ci_ ₆ )alkyl,

-(C ₂ . ₆ )alkyl-OH, -(C _1-6 )alkyl-SO ₃ , -(C _2-6 )alkyl-OSO ₃ ^" , -(C _1-6 )alkyl-PO ₃ H ^" , -(C _2-6 )alkyl-OPO ₃ H ^" , -(C^alkyl-COO , or at least two of R ⁵ , R ⁶ and R ⁷ are joined, together with the N atom to which they are attached, to form a heterocycle containing one N heteroatom and optionally from 1 to 3 further heteroatoms each independently selected from N, O and S, the heterocycle being optionally substituted with from one to three substituents each independently selected from (C _1-6 )alkyl and aryl

[0072] The compounds of the present invention are useful as surfactants Such surfactants can be used as components of fluids used in the petroleum industry for the production or recovery of petroleum from petroleum-bearing formations, in applications including but not limited to drilling, completion, work over or servicing of oil and gas wells, treatment of oil and gas bearing formations, enhancement of production from oil and gas bearing formations, bioremediation, hydraulic fracturing, and well stimulation, including but not limited to chemical flooding oil recovery and foam flooding oil recovery, and other methods of secondary and tertiary oil and heavy oil recovery In at least one embodiment, compounds according to the present invention having zwitterionic or amphoteric headgroups, or which exhibit the property of viscoelasticity, can be friction pressure reducing agents for the preparation of well stimulation fluids, including but not limited to those used in fracturing and acidizing fluids. In addition, in at least one embodiment, the compounds of the present invention can be used as agents for shale stabilization, including but not limited to when drilling in gumbo and in young, easily hydrated rock formations. In at least one embodiment, the compounds of the present invention can also be used as super shale inhibitors in water-based fluid systems where the use of potassium salts and amine salts of the ethylene diamine type have proven ineffective, and/or are prohibited due to environmental constraints. [0073] Another aspect of the present invention provides a fluid for use in the production or recovery of petroleum from petroleum-bearing formations, including but not limited to drilling, completion, work over or servicing of oil and gas wells, treatment of oil and gas bearing formations, enhancement of production from oil and gas bearing formations, bioremediation, hydraulic fracturing, and well stimulation, including but not limited to chemical flooding oil recovery and foam flooding oil recovery, the fluid comprising a compound according to the present invention as defined herein, a base fluid and optionally at least one chemical additive. In at least one embodiment, when the fluid is used for hydraulic fracturing, the compound according to the present invention can advantageously form micelles which are worm-like in nature, thereby acting to impart the property of viscoelasticity to the fluid.

[0074] According to another aspect of the present invention, there is provided a method for using a fluid comprising a compound according to the present invention as defined herein in the production or recovery of petroleum from petroleum-bearing formations, including but not limited to drilling, completion, work over or servicing of oil and gas wells, treatment of oil and gas bearing formations, enhancement of production from oil and gas bearing formations, bioremediation, hydraulic fracturing, and well stimulation, including but not limited to chemical flooding oil recovery and foam flooding oil recovery.

[0075] In at least one embodiment, the fluid is a fabricated fluid suitable for use in the drilling, completion, work over or servicing of oil and gas wells, treatment of oil and gas bearing formations, enhancement of production from oil and gas bearing formations, hydraulic fracturing, and well stimulation, including but not limited to chemical flooding oil recovery and foam flooding oil recovery.

[0076] According to yet another aspect of the present invention, there is also provided a method of preparing a fluid for use in drilling, completion, work over or servicing of oil and gas wells, treatment of oil and gas bearing formations, enhancement of production from oil and gas bearing formations, hydraulic fracturing, or well stimulation, including but not limited to chemical flooding oil recovery and foam flooding oil recovery, the method comprising adding a predetermined amount of a compound according to the present invention to a base fluid and mixing the compound according to the present invention and the base fluid. In at least one embodiment the base fluid comprises at least one chemical additive.

[0077] Suitable base fluids can be chosen by the skilled person based at least partly on the specific purpose of the fluid, as will be appreciated by the person of skill in the art, and include, but are not limited to, aqueous base fluids and non-aqueous base fluids, including but not limited to hydrocarbon base fluids, such as, for example, diesel oil, and synthetic base fluids.

[0078] Chemical additives which may be added to a fluid, including but not limited to a drilling fluid, for use in the production or recovery of petroleum from petroleum-bearing formations include but are not limited to weight materials, fluid loss control agents, bridging agents, lubricants, anti-bit balling agents, corrosion inhibition agents, surfactants and suspending agents. Such components can be added in the concentrations needed to adjust the rheological and functional properties of the drilling fluid appropriate to the drilling conditions, as would be apparent to the skilled person. Suitable examples of each of these additional components are well known to the person of skill in the art.

[0079] Weight materials are inert, high-density particulate materials used to increase the density of the drilling fluid. Suitable weight materials are known in the art and include, but are not limited to such examples as calcium carbonate, magnesium carbonate, iron oxide, barite, hematite, ilmenite, water-soluble organic and inorganic salts, and mixtures thereof.

[0080] Fluid loss control agents are added to drilling fluids to help prevent or reduce fluid loss during the drilling process. Suitable examples of fluid loss control agents include but are not limited to synthetic organic polymers including but not limited to polyacrylate; biopolymers including but not limited to starches, modified starches and modified celluloses; modified lignite; lignosulfonate; silica; mica; calcite; and mixtures thereof.

[0081] Bridging agents are materials added to a drilling fluid to bridge across pores and fractures of exposed rock, to seal formations, and to aid in forming a filter cake. Advantageously, bridging agents are removable from the wellbore after drilling is complete, to facilitate recovery when the well enters production. Suitable examples of bridging agents include but are not limited to magnesium oxide, manganese oxide, calcium oxide, lanthanum oxide, cupric oxide, zinc oxide, magnesium carbonate, calcium carbonate, zinc carbonate, calcium hydroxide, manganese hydroxide, suspended salts, oil-soluble resins, mica, nutshells, fibers and mixtures thereof.

[0082] Lubricants are used to lower friction, including but not limited to torque and drag in the wellbore, and to lubricate unsealed bit bearings. Suitable examples of lubricants include but are not limited to plastic beads, glass beads, nut hulls, graphite, oils, synthetic fluids, glycols, modified vegetable oils, fatty-acid soaps, surfactants and mixtures thereof.

[0083] Anti-bit balling agents are used to prevent compaction and adherence of drill cuttings to the cutting surfaces of the drill bit, causing fouling and a reduction of drill performance. Suitable examples of anti-bit balling agents include but are not limited to glycols, surfactants and mixtures thereof.

[0084] Corrosion inhibition agents are used to protect the metal components of the drill from corrosion caused by contact with materials such as water, carbon dioxide, biological deposits, hydrogen sulfide and acids. Suitable examples of corrosion inhibition agents include but are not limited to amines, zinc compounds, chromate compounds, cyanogen- based inorganic compounds, sodium nitrite based compounds and mixtures thereof.

[0085] Surfactants are surface active agents that can function as emulsifiers, dispersants, oil-wetters, water-wetters, foamers and defoamers. Suitable examples of surfactants include but are not limited to anionic surfactants, cationic surfactants, zwitterionic surfactants, nonionic surfactants, and suitable mixtures of any of the above known to one skilled in the art.

[0086] Suspending agents alter the rheological and viscosity properties of the drilling fluid, thereby allowing small solid particles to remain suspended in the fluid. Suitable examples of suspending agents include but are not limited to clays, biopolymers, gums, silicates, fatty acids, synthetic polymers and mixtures thereof.

[0087] The compounds of the present invention can also be used to accelerate bioremediation, or the bacterial removal of oil from cuttings formed during the drilling of oil wells. Without being bound by theory, it is believed that the present compounds can aid the removal of grease and oil from the cuttings due to their wetting ability and their ability to lower surface and interfacial tension. In this way, these compounds, when added to drilling fluids, can act to increase the bioavailability of the oil to the bacteria used in the remediation cycle, so as to facilitate bioremediation of the cuttings. Therefore, according to another aspect of the present invention, there is provided a method for the bioremediation of cuttings produced during the drilling of a well bore from a fluid used to transport the cuttings from the bottom of said well bore to the surface, wherein the fluid comprises an experimentally determined amount of a compound according to the present invention as defined herein.

[0088] According to yet another aspect of the present invention, there is also provided a method of fracturing an underground hydrocarbon bearing formation penetrated by a well bore, comprising the steps of injecting a stream of fluid comprising a compound according to the present invention into the formation at a pressure selected to cause the formation of at least one fracture in the formation. In at least one embodiment, the compound according to the invention can form micelles which are worm-like in nature, thereby acting to impart the property of viscoelasticity to the fluid. In at least one embodiment, the fluid further comprises at least one proppant, used to prop open the fracture. Suitable proppants include but are not limited to graded sand, bauxite, ceramics, and nut hulls.

[0089] According to yet another aspect of the present invention, there is also provided a method of reducing turbulent flow in a fluid flowing past a stationary object, the method comprising adding a compound according to the present invention to the fluid. In at least one embodiment, the stationary object is a pipe wall, an earth formation, a boat bottom or a surface encountered in central heating distribution.

[0090] Compositions containing compounds of the present invention can also be envisioned to have applications in other industries besides the petroleum industry. For example, the compounds of the present invention would be suitable in cleansing compositions or detergent compositions, including, but not limited to hair shampoos, hair conditioners, cream cleansers, body washes, dishwashing liquids, dishwashing powders and laundry detergents. Detergent compositions containing surfactants according to the present invention can be prepared or used in any known forms, e.g. in solid, liquid, cream, foam, or powder form. Such detergent compositions can, by someone skilled in the art, be made into any of a number of well known desirable forms such as bars, granules, flakes, liquids, and tablets. The detergent formulations incorporating or embodying the novel surfactants of the present invention may contain any of the usual adjuvants, diluents and additives, including but not limited to perfumes, antitarnishing agents, anti-redeposition agents, anti-bacterial agents, dyes, fluorescent agents, suds builders, suds depressors, foam stabilizers and co-surfactants. Suitable co-surfactants can include other well known natural soaps or synthetic anionic, non-ionic, zwitterionic, or amphoteric amphiphiles. As a non-limiting example, contemplated detergent formulations would comprise blending a surfactant of the present invention with a detergency builder. The amount and type of the surfactant of the present invention usefully present in the detergent formulations will depend on the application, and would be determined experimentally by any of a number of known methods. It is to be understood that contemplated detergent formulations comprising at least one surfactant according to the present invention are not limited to any particular method of preparation.

[0091] Emulsion compositions containing the surfactants of the present invention are also contemplated. In this application, the amount of surfactant may vary, and can be determined by any of a number of standard techniques known by those skilled in the art. The emulsion composition of the invention can contain the surfactant, water, and oil components usually blended into an emulsion composition. Suitable oil components include but are not limited to liquid oils, solid oils, waxes, hydrocarbon oils, higher fatty acids, higher alcohols, synthetic ester oils, silicone oils, etc. Where necessary, the emulsion composition may additionally contain other surfactants and additives which are usually blended into an emulsion composition. Suitable other surfactants include but are not limited to anionic surfactants , amphoteric surfactants , nonionic surfactants

(lipophilic, hydrophilic), and cationic surfactants. Suitable additives include but are not limited to humectants, powdery components, water-soluble polymers, viscosity improvers, UV absorbents, metal ion sequestering agents, lower alcohols, polyhydric alcohols, saccharides (monosaccharides, oligosaccharides, and polysaccharides), amino acids, organic amines, pH controlling agents, antioxidants, auxiliary antioxidants, preservatives, antiphlogistics, whitening agents, extracts, activating agents, circulation stimulants, anti-seborrhea agents, and anti-inflammatory agents.

[0092] Suitable formulation of the surfactants of the present invention into an emulsion composition by someone of skill in the art will ensure a good emulsion state. The emulsion compositions containing the invented surfactants can be used in any known forms such as creams, liquids, or gels. The emulsion composition can suit any of a number of known applications containing said emulsion, including but not limited to known cosmetics (creams, milky lotions, and serums), pharmaceuticals, medicated cosmetics, and foods. [0093] The surfactants of the present invention can also be used for a number of other well-known surfactant applications, including but not limited to scouring agents, foaming agents, defoamers, demulsifying agent, dispersants, wetting agents, dissolving agents, lustering agents, delustering agents, softening agents, water repellents, flame repellents, antistatic agents, and flotation agents. Synthetic Methodology

[0094] Compounds of general formula I

wherein R ¹ , R ² , R ³ and R ⁴ are as defined herein, are conveniently prepared by the procedures illustrated in the following schemes. It will be apparent to the skilled person that other procedures well known in the art may be used in the preparation of the present compounds. The skilled person will also recognize that the procedures described herein will also be applicable to the synthesis of compounds of the formula IA

IA wherein A is a core derived from other organic polyhdroxy compounds. Scheme 1

[0095] Mono-O-benzylidenepentaerythritol (II) is prepared by the method of lssidorides and Gulen (Organic Syntheses Collected Volume IV, Rabjohn, N., Ed.; John Wiley and Sons: New York, 1963; pp 679-681.) Treatment of mono-O-benzylidenepentaerythritol with sodium hydride followed by an alkylating agent, including but not limited to an alkyl halide or an arylalkyl halide, under well-known conditions, provides intermediate III, wherein R ¹ and R ² are alkyl or arylalkyl. Hydrogenolysis of intermediate III provides intermediate IV. It will be apparent to the skilled person that other well-known protecting groups, including but not limited to other acetals, can be used in the preparation of intermediate IV. [0096] Intermediate IV is transformed to intermediate V by reaction with sodium hydride, followed by a reagent of formula X-Y-N(R ⁵ )(R ⁶ ), wherein X is a leaving group, Y is (C ₂ - ₆ )alkyl, and R ⁵ and R ⁶ are as defined herein. Such a reagent can be in the form of a salt, including but not limited to the hydrochloride salt. Intermediate V can be treated with an acid, including but not limited to hydrochloric acid, to give compounds of formula I wherein R ¹ and R ² are alkyl or arylalkyl and R ³ and R ⁴ are -OY-N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ , wherein R ⁷ is H. Alternatively, intermediate IV can be allowed to react with an alkylating agent of formula R ^7a -X, wherein X is a leaving group and R ^7a is R ⁷ as defined herein or a group which may be subsequently transformed to R ⁷ , to give compounds of formula I wherein R ¹ and R ² are alkyl or arylalkyl and R ³ and R ⁴ are -OY-N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ . It will be clear to the person of skill in the art that when R ⁷ is a -(CveJalkyl-COO ^" group, R ^7a can have the formula -(C^alkyl-COOP, wherein P is a protecting group, including but not limited to an alkyl group, which may readily be removed, by well known procedures, including but not limited to hydrolysis, to form R ⁷ .

Scheme 2

[0097] Reaction of intermediate IV with I ₂ and PPh ₃ under well known conditions, or using other well-known procedures, provides intermediate Vl, wherein R ¹ and R ² are as defined herein. Intermediate Vl can be allowed to react with an amine of formula HN(R ⁵ )(R ⁶ ), wherein R ⁵ and R ⁶ are as defined herein, followed by acidification, to give compounds of formula I wherein R ¹ and R ² are alkyl or arylalkyl, and R ³ and R ⁴ are -NH(R ⁵ )(R ⁶ ) ⁺ . Alternatively, intermediate Vl can be allowed to react with an amine of formula HN(R ⁵ )(R ⁶ ), wherein R ⁵ and R ⁶ are as defined herein, followed by acidification or alkylation with an alkylating agent of formula R ^7a -X, wherein X is a leaving group and R ^7a is R ⁷ as defined herein or a group which may be subsequently transformed to R ⁷ , to give compounds of formula I wherein R ¹ and R ² are alkyl or arylalkyl, and R ³ and R ⁴ are -N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ .

[0098] Furthermore, intermediate Vl can be transformed to compounds of formula I by the procedure illustrated in Scheme 3.

Scheme 3

[0099] Reaction of intermediate Vl with KCN provides intermediate VII, which can be hydrolyzed by procedures well known in the art, including but not limited to hydrolysis in the presence of NaOH, to give intermediate VIII. Intermediate VIII is allowed to react with an amine of formula HN(R ⁵ )(R ⁶ ), wherein R ⁵ and R ⁶ are as defined herein, under well known conditions, including but not limited to reaction in the presence of 1 -hydroxybenzotriazole and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride to give intermediate IX. Reduction of the amide functionality of intermediate IX using well known reagents including but not limited to LiAIH ₄ , provides compounds of formula I wherein R ¹ and R ² are alkyl or arylalkyl and R ³ and R ⁴ are -CH ₂ N(R ⁵ )(R ⁶ ). Acidification or alkylation with an alkylating agent of formula R ^7a -X, wherein X is a leaving group and R ^7a is R ⁷ as defined herein or a group which may be subsequently transformed to R ⁷ , provides compounds of formula I wherein R ¹ and R ² are alkyl or arylalkyl, and R ³ and R ⁴ are -CH ₂ N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ . Scheme 4

[00100] Intermediate Vl can be oxidized to intermediate X under well known conditions, including but not limited to Swern oxidation conditions. Intermediate X can be transformed to intermediate Xl by reactions known in the art, including but not limited to the Wadsworth-Horner-Emmons reaction. Hydrogenation of intermediate Xl under well known conditions provides compound XII, which is reduced, by well known reagents, including but not limited to LiAIH ₄ , to give compounds of formula I wherein R ¹ and R ² are alkyl or arylalkyl and R ³ and R ⁴ are -CH ₂ CH ₂ N(R ⁵ )(R ⁶ ). Acidification or alkylation with an alkylating agent of formula R ^7a -X, wherein X is a leaving group and R ^7a is R ⁷ as defined herein or a group which may be subsequently transformed to R ⁷ , provides compounds of formula I wherein R ¹ and R ² are alkyl or arylalkyl, and R ³ and R ⁴ are -CH ₂ CH ₂ N(R ⁵ )(R ⁶ )(R ⁷ ) ⁺ .

Scheme 5

XlIl

[00101] Compounds of formula I ₁ wherein R ¹ is as defined herein, R ² is R ¹ , and R ³ and R ⁴ are -OSO ₃ ^" , can be prepared by reacting pentaerythritol bicyclic sulfate (XIII), prepared by the methods of Gulyas, H.; Dobό, A.; Bakos, J. Can. J. Chem. 2001, 79, 1040-1048 and/or Gulyas, H.; Arva, P.; Bakos, J. Chem. Commun. 1997, 2385-2386, with an alcohol of formula R ¹ -OH in the presence of sodium hydride and N ₁ N- dimethylformamide.

Scheme 6

[00102] Reaction of intermediate IV, wherein R ¹ and R ² are alkyl or arylalkyl, with sodium hydride, followed by a (C ₂ - ₆ )alkylene sulfate, provides compounds of formula I wherein R ¹ and R ² are alkyl or arylalkyl, and R ³ and R ⁴ are -O(C _2-6 )alkyl-OSO ₃ ^' . Alternatively, reaction of intermediate IV, wherein R ¹ and R ² are alkyl or arylalkyl, with sodium hydride, followed by a (C ₂ - ₆ )sultone, provides compounds of formula I wherein R ¹ and R ² are alkyl or arylalkyl, and R ³ and R ⁴ are -O(C ₂ . ₆ )alkyl-SO ₃ ^" .

EXAMPLES

[00103] Other features of the present invention will become apparent from the following non-limiting examples which illustrate, by way of example, the principles of the invention. It will be apparent to a person of skill in the art that the procedures exemplified below may be used, with appropriate modifications, to prepare other compounds of the invention as described herein. The examples described herein serve to illustrate the utility of the synthetic methods and the materials developed from those methods in the production of compounds according to the invention, and are not meant to be all- inclusive.

[00104] Λ/,Λ/-Dimethylformamide is stored over activated molecular sieves for 72 hours, then distilled with reduced pressure over more activated molecular sieves. Methanol is dried with magnesium methoxide. Toluene is dried by reflux over calcium hydride for 10 min followed by distillation from calcium hydride. Sodium hydride is a 60% oil dispersion that is washed with dry hexane under nitrogen before use. Reactions involving sodium hydride are performed in flame-dried glassware. ¹ H and ¹³ C NMR spectra are recorded at 300 K in 5 mm NMR tubes on a Bruker AC-250 MHz spectrometer operating at 250.13 and 62.9 MHz, respectively or on a Bruker AVANCE-500 NMR operating at 500.13 and 125.08 MHz, respectively, on solutions in chloroform-d, unless otherwise indicated. Chemical shifts are given in parts per million (ppm)(+/-0.01 ppm) relative to that of tetramethylsilane (TMS) (0.00 ppm) in the case of ¹ H NMR spectra, and to the central line of chloroform-d (δ=77.16) for ¹³ C NMR spectra. All assignments are made with the aid of COSY (COrelation Spectroscopy), HETCOR (HETeronuclear CORrelation), and/or long-range HETCOR experiments at 250 MHz or HSQC (Heteronuclear Single Quantum Correlation) or HMBC (Heteronuclear Multiple Bond Correlation) experiments at 500 MHz. High resolution electrospray mass spectra (HR ESI MS) arere recorded on samples dissolved in methanol using trilysine KKK or rifampicin or the Tuning Mix from Agilent as references. Most thin layer chromatography (TLC) is performed on aluminum- backed plates bearing 200 μm silica gel 60 F _2S4 (Merck or Silicycle). Benzylidene acetals are visualized by quenching of fluorescence or by spraying the plate with a solution of 0.2 % p-methoxyphenol in ethanol/2N H ₂ SO ₄ (1/1 , v/v), as described in Herzner, H.; Eberling, J.; Schultz, M.; Zimmer, J.; Kunz, H. J. Carbohydr. Chem. 1998, 17, 759-776, or an acidic solution of anisaldehyde in ethanol [ethanol (9 ml_), anisaldehyde (0.5 ml_), and cone, sulfuric acid (0.5 ml_), as described in Stahl, E.; Kaltenbach, U. J. Chromatogr. 1961, 5, 351-355], or a solution of 2% eerie sulfate in 1 M sulfuric acid, and followed, for all spray reagents, by heating on a hot plate until colour developed. TLC for quaternary ammonium salts is performed on aluminum-backed plates bearing 200 μm basic alumina and developed with the Dragendorff reagent (Thies, H.; Reuther, F.W. Naturwissenschaften 1954, 41, 230-231 ; Vagύjfalvi, D. Planta Med. 1960, 8, 34-43; Stahl, E. Thin Layer Chromatography: A Laboratory Handbook; 2nd ed.; Springer: Heidelberg, 1969, p. 874). Example 1A

5,5'-Bis(octyloxymethyl)-2-phenyl-1 ,3-dioxane (1 a)

1a

[00105] Sodium hydride (60% oil dispersion, washed with hexanes, 8.6 g, 0.22 mol, 2.0 5 eq) is added in portions slowly to a stirred solution of mono-O-benzylidenepentaerythritol (II, Scheme 1 , prepared by the method of Issidorides, C. H.; Gulen, R. C. Organic Syntheses Collected Volume IV, Rabjohn, N., Ed.; John Wiley and Sons: New York, 1963; pp 679-681) (24.11 g, 0.1076 mol) in dry DMF (600 ml_) under a nitrogen atmosphere. The stirred reaction mixture is cooled with an ice water bath for one hour,

10 then 1-bromooctane (46.76 ml_, 51.90 g, 0.268 mol, 2.5 eq) is added dropwise over 2 h. After the reaction mixture has been stirred 12 h, another addition of sodium hydride (4.5 g, 0.11 mol, 1.0 eq) and 1-bromooctane (20 ml_, 0.11 mol, 1.0 eq) is made. If after the reaction mixture has been stirred a further 12 h, TLC shows that some mono-O-octyl product is present, another identical addition is made. When all of the mono-O-octyl

15 derivative has been consumed, the reaction mixture is quenched by the addition of methanol dropwise until foaming ceases. The reaction mixture is filtered under vacuum and the reaction flask and filter are washed with dichloromethane (~150 ml_). The combined filtrate and washings are concentrated and the residue is extracted with hexanes (300 mL, then 200 ml_). The combined extracts are washed with water (100

20 mL), dried (MgSO ₄ ) and concentrated under reduced pressure to an oily residue that is passed through a short silica gel column using hexanes, then 5% ethyl acetate/95% hexanes as eluents. The title compound (1a) is a colourless oil (44.71 g, 93 %): R _F 0.46 (94 : 6, hexanes : ethyl acetate); ¹ H NMR (500.13 MHz) δ 0.88, 0.89 (2 t, 6H, J = 6.5 Hz, 2 x Me), 1.20-1.35 (br m, 2OH, 10 x CH ₂ ), 1.54, 1.57 (2 pentet, 4H, J = 6.8 Hz, 2

25 OCH ₂ CH ₂ ), 3.22 (s, 2H, eq CCH ₂ O), 3.35 (t, 2H, J = 6.5 Hz, eq octyl OCH ₂ ), 3.45 (t, 2H, J = 6.6 Hz, ax octyl OCH ₂ ), 3.71 (s, 2H, ax OCH ₂ C), 3.88, 4.09 (2d, 4H, J = 11.5 Hz, H- 4,H-4', H-6.H-6'), 5.42 (s, 1 H, acetal H), 7.31-7.49 (m, 5H, Ph); ¹³ C NMR δ 138.5 (q Ph) , 128.8 (para Ph), 128.3 (2C, mPh), 126.1 (2C, oPh), 101.7 (acetal C), 71.8 (eq OCH ₂ CH ₂ ), 71.7 (ax OCH ₂ CH ₂ ), 70.8 (eq OCH ₂ C), 70.2 (C-4 and C-6), 69.4 (ax OCH ₂ C),

30 38.9 (q C), 2 x 31.89 (CH ₂ CH ₂ CH ₃ ), 29.68, 29.54, 29.51 , 29.45, 2 x 29.34 (6 octyl CH ₂ ), 26.22, 26.19 (CH ₂ CH ₂ CH ₂ O), 2 x 22.70 (CH ₂ CH ₃ ), 14.3 (Me); MS ESI: CaIc for C ₂₈ H ₄₉ O ₄ 449.3631 , found 449.2; calc for C ₂₈ H ₄₈ O ₄ Na ⁺ 471.35, found 471.3; calc for (C ₂₈ H ₆₈ O ₄ ) ₂ Ca ²⁺ 468.34, found 468.5; calc for C ₂₈ H ₄₈ O ₄ K ⁺ 487.32, found 487.3.

Example 1 B 5 5,5'-Bis(decyloxymethyl)-2-phenyl-1,3-dioxane (1b)

1b

[00106] The reaction of mono-O-benzylidenepentaerythritol (II, Scheme 1 , prepared by the method of Issidorides, C. H.; Gulen, R. C. Organic Syntheses Collected Volume IV, Rabjohn, N., Ed.; John Wiley and Sons: New York, 1963; pp 679-681) (25.1 g, 0.112

10 mol), sodium hydride (60 % oil dispersion, washed with hexanes, 8.95 g, 0.224 mol, 2.0 eq) and 1-bromodecane (57.9 ml_, 61.9 g, 0.280 mol, 2.5 eq) in dry DMF (600 mL) is performed as for Example 1A using additional additions of sodium hydride (1.0 eq) and 1-bromodecane (1.0 eq) as needed. Concentration gives a yellowish oil (50.3 g, 89.1%) that is filtered using a short silica gel column (eluent hexanes). The resulting solution is

15 concentrated to a colourless oil that is crystallized from methanol: mp 29-30 ⁰ C; R _F 0.48 (94: 6 hexanes:ethyl acetate); ¹ H NMR δ 0.88 (t, 6H, J = 6.4 Hz, 2 x Me), 1.20-1.35 (br s, 28H, 14 x CH ₂ ), 1.54 (pentet, 4H, J = 6.7 Hz, 2 OCH ₂ CH ₂ ), 3.23 (s, 2H, eq CCH ₂ O), 3.36 (t, 2H, J = 6.4 Hz, eq decyl OCH ₂ ), 3.46 (t, 2H, J = 6.6 Hz, ax decyl OCH ₂ ), 3.71 (s, 2H, ax OCH ₂ C), 3.88, 4.09 (2d, 4H, J = 11.7 Hz, H-4, H-4', H-6, H-6'), 5.42 (s, 1 H, acetal H),

20 7.31-7.48 (m, 5H, Ph); ¹³ C NMR δ 138.6 (q Ph) , 129.0 (para Ph), 128.4 (2C, mPh), 126.2 (2C, oPh), 101.9 (acetal C), 71.9 (eq OCH ₂ CH ₂ ), 71.8 (ax OCH ₂ CH ₂ ), 70.9 (eq OCH ₂ C), 70.4 (C-4 and C-6), 69.4 (ax OCH ₂ C), 39.0 (q C), 2 x 32.06 (CH ₂ CH ₂ CH ₃ ), 2 x 29.81 , 29.79, 2 x 29.76, 29.69, 29.65, 29.62, 2 x 29.50 (10 decyl CH ₂ ), 2 x 26.3 (CH ₂ CH ₂ CH ₂ O), 2 x 22.8 (CH ₂ CH ₃ ), 14.3 (Me); MS ESI: Calc for C ₃₂ H ₅₇ O ₄ 505.4, found

25 505.1. Anal. Calc. for C ₃₂ H ₅₆ O ₄ : C 76.14, H 11.18. Found: C 76.03, H 10.97. Example 1C

5,5'-Bis(dodecyloxymethyl)-2-phenyl-1 ,3-dioxane (1c)

H ₃ C(H ₂ C) ₁₁ 0(CH ₂ J ₁₁ CH ₃

1c

[00107] The reaction of mono-O-benzylidenepentaerythiϊtol (II, Scheme 1 , prepared by the method of Issidorides, C. H.; Gulen, R. C. Organic Syntheses Collected Volume IV, Rabjohn, N., Ed.; John Wiley and Sons: New York, 1963; pp 679-681) (30.0 g, 0.134 mol), sodium hydride (60 % oil dispersion, washed with hexanes, 12 g, 0.30 mol, 2.2 eq) and 1-bromododecane (72 ml_, 74.88 g, 0.30 mol, 2.25 eq) in dry DMF (1000 ml.) is performed as for Example 1A using additional additions of sodium hydride (1.0 eq) and 1-bromododecane (1.0 eq) as needed. The residue is a solid that is recrystallized from methanol to give colorless needles: yield 57.54 g, 77%; R _F 0.51 (94:6 hexanes:ethyl acetate); mp 37.5 - 38.5 ⁰ C; ¹ H NMR δ 0.88 (t, 6H, J = 6.4 Hz, 2 x Me), 1.20-1.35 (br s, 36H, 18 x CH ₂ ), 1.54 (pentet, 4H, J = 6.3 Hz, 2 OCH ₂ CH ₂ ), 3.22 (s, 2H, eq CCH ₂ O), 3.35 (t, 2H, J = 6.5 Hz, eq dodecyl OCH ₂ ), 3.46 (t, 2H, J = 6.6 Hz, ax dodecyl OCH ₂ ), 3.71 (s, 2H, ax OCH ₂ C), 3.88, 4.09 (2d, 4H, J = 11.7 Hz, H-4, H-4', H-6, H-6'), 5.41 (s, 1 H, acetal H), 7.31-7.48 (m, 5H, Ph); ¹³ C NMR δ 138.5 (q Ph), 128.8 (para Ph), 128.2 (2C, mPh), 126.1 (2C, oPh), 101.7 (acetal C), 71.7 (eq CH ₂ CH ₂ OC), 71.6 (ax CH ₂ CH ₂ OC), 70.7 (eq OCH ₂ C), 70.2 (C-4 and C-6), 69.3 (ax OCH ₂ C), 38.9 (q C), 2 x 31.8 (CH ₂ CH ₂ CH ₃ ), 29.70, 29.66, 29.61 , 29.53, 29.22 (14 dodecyl CH ₂ ), 26.2 (CH ₂ CH ₂ CH ₂ O), 2 x 22.7 (CH ₂ CH ₃ ), 2 x 14.1 (Me); MS ESI: CaIc for C ₃₆ H ₆₅ O ₄ 561.49, found 561.3; calc for C ₃₆ H ₆₄ O ₄ Na ⁺ 583.47, found 583.5; calc for C ₃₆ H ₆₄ O ₄ K ⁺ 599.44, found 599.3. Anal. Calc. for C ₃₆ H ₆₄ O ₄ : C 77.09, H 11.50. Found: C 77.04, H 11.92. Example 1 D

2-Phenyl-5,5'-bis(tetradecyloxymethyl)-1 ,3-dioxane (1 d)

H ₃ C(H ₂ C) ₁₃ O(CH2) ₁₃ CH ₃

1d

[00108] The reaction of mono-0-benzylidenepentaerythritol (H, Scheme 1 , prepared by the method of Issidorides, C. H.; Gulen, R. C. Organic Syntheses Collected Volume IV, Rabjohn, N., Ed.; John Wiley and Sons: New York, 1963; pp 679-681) (30.0 g, 0.134 mol), sodium hydride (60 % oil dispersion, washed with hexanes, 11.3 g, 0.295 mol, 2.2 eq) and 1-bromotetradecane (84 mL, 78.3 g, 0.282 mol, 2.5 eq) in dry DMF (1000 ml_) is performed as for Example 1 A using additional additions of sodium hydride (1.0 eq) and 1-bromotetradecane (1.0 eq) as needed to give the title compound (1d) as a solid (73.7 g, 89%): R _F 0.53 (94:6 hexanes:ethyl acetate); recrystallized from ethyl acetate; mp 45°C; ¹ H NMR (500 MHz) δ 0.88 (t, 6H, J = 6.6 Hz, 2 x Me), 1.16-1.37 (br s, 44H, 18 x CH ₂ ), 1.55 (br pentet, 4H, J = 6.4 Hz, 2 OCH ₂ CH ₂ ), 3.23 (s, 2H, eq CCH ₂ O), 3.35 (t, 2H, J = 6.4 Hz, eq OCH ₂ CH ₂ ), 3.46 (t, 2H, J = 6.4 Hz, ax OCH ₂ CH ₂ ), 3.71 (s, 2H, ax OCH ₂ C), 3.88, 4.09 (2d, 4H, J = 11.3 Hz, H-4.H-4', H-6.H-6 ¹ ). 5.41 (s, 1 H, acetal H), 7.31-7.48 (m, 5H, Ph); ¹³ C NMR δ 139.3 (q Ph) , 128.9 (para Ph), 128.4 (2C, mPh), 126.2 (2C ₁ oPh), 101.8 (acetal C), 71.9 (eq CH ₂ CH ₂ OC), 71.8 (ax CH ₂ CH ₂ OC), 70.9 (eq OCH ₂ C), 70.4 (C- 4 and C-6), 69.5 (ax OCH ₂ C), 39.0 (q C), 2 x 32.1 (CH ₂ CH ₂ CH ₃ ), 2 x 29.86, 2 x 29.83, 6 x 29.81 , 2 x 29.77, 2 x 29.75, 2 x 29.66, 2 x 29.51 (18 tetradecyl CH ₂ ), 2 x 26.3 (CH ₂ CH ₂ CH ₂ O), 2 x 22.8 (CH ₂ CH ₃ ), 2 x 14.2 (Me); MS ESI: CaIc for C ₄₀ H ₇₃ O ₄ 617.5509, found 617.1 ; CaIC fOr C ₄₀ H ₇₂ O ₄ Na 639.53, found 639.5; calc for C ₄₀ H ₇₂ O ₄ K 655.51 , found 655.3.

Example 2A

2,2-Bis(octyloxymethyl)-1 ,3-propanediol (2a)

H ₃ C(H ₂ C) ₇

2a [00109] To a solution of compound 1a (Example 1A) (10.02 g, 22.3 mmol) in ethyl acetate (100 mL) is added 10% Pd/C (Degussa type, 0.2 g). The mixture is stirred vigorously under atmospheric pressure H ₂ (g) for 1 h. More 10% Pd/C (Degussa type, 0.5 g) is added and the solution stirred until uptake of H ₂ (g) ceases (2 h). The mixture is filtered and the residue washed with dichloromethane (50 mL), then dichloromethane containing 20% methanol (2 x 50 mL). The filtrate and washings are concentrated to a colourless solid that is recrystallized from methanol: yield 6.89 g, 85%, R _F 0.40 (dichloromethane: methanol 96:4); mp 30-32 ⁰ C. Recrystallization from isopropanol gives colorless crystals: mp 35°C; ¹ H NMR δ 0.88 (t, 6H, J = 6.9 Hz, 2 x Me), 1.20-1.36 (br m, 2OH, 10 x CH ₂ ), 1.56 (pentet, 4H, J = 6.8 Hz, 2 OCH ₂ CH ₂ ), 2.82 (t, 2H, J = 6.1 Hz, OH), 3.42 (t, 4H, J = 6.5 Hz, octyl OCH ₂ ), 3.50 (s, 4H, OCH ₂ C), 3.65 (d, 4H, CH ₂ OH); ¹³ C NMR δ 73.1 (CCH ₂ OCH ₂ CH ₂ ), 72.2 (CH ₂ CH ₂ OC), 65.5 (CH ₂ OH), 44.7 (q C), 31.9 (CH ₂ CH ₂ CH ₃ ), 29.50, 29.35 (2 octyl CH ₂ ), 29.64 (OCH ₂ CH ₂ ), 26.3 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.2 (Me); MS ESI: CaIC fOr C _2I H ₄₅ O ₄ 361.33, found 361.1. Anal. CaIc. for C ₂₁ H ₄₄ O ₄ : C 69.95, H 12.30. Found: C 69.62, H 12.68.

Example 2B

2,2-Bis(decyloxymethyl)-1 ,3-propanediol (2b)

H ₃ C(H ₂ C) ₉

[00110] Compound 1b (Example 1B) (10.23 g, 20.3 mmol) is hydrogenated using the procedure of Example 2A in ethyl acetate (100 mL) using 10% Pd/C (Degussa type, 0.2 g) as catalyst to give a colourless solid that is recrystallized from methanol: yield 6.81g, 80.7%, R _F 0.42 (dichloromethane: methanol 96:4); mp 44.5-45°C; ¹ H NMR δ 0.88 (t, 6H, J = 6.6 Hz, 2 x Me), 1.20-1.35 (br s, 28H, 18 x CH ₂ ), 1.55 (pentet, 4H, J = 6.5 Hz, 2 OCH ₂ CH ₂ ), 2.88 (t, 2H, J= 6.1 Hz, OH), 3.42 (t, 4H, J = 6.5 Hz, dodecyl OCH ₂ ), 3.51 (s, 4H, OCH ₂ C), 3.65 (d, 4H, CH ₂ OH); ¹³ C NMR δ 73.3 (CCH ₂ OCH ₂ CH ₂ ), 72.2 (CH ₂ CH ₂ OC), 65.6 (CH ₂ OH), 44.6 (q C), 32.0 (CH ₂ CH ₂ CH ₃ ), 3 x 29.7, 29.66, 29.56, 29.47 (6 dodecyl CH ₂ ), 26.3 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.2 (Me); MS ESI: CaIc for C ₂₅ H ₅₃ O ₄ 417.39, found 417.1. Anal. CaIC fOr C ₂₅ H ₅₂ O ₄ : C 72.06, H 12.58. Found: C 71.98, H 12.45. Example 2C

2,2-Bis(dodecyloxymethyl)-1 ,3-propanediol (2c)

CH ₃

2c

[00111] Compound 1c (Example 1C) (10.23 g, 20.3 mmol) is hydrogenated using the procedure of Example 2A in ethyl acetate (100 ml.) using 10% Pd/C (Degussa type, 0.2 g) as catalyst to give a colourless solid that is recrystallized from ethyl acetate: yield 6.81 g, 80.7%; R _F 0.45 (dichloromethane: methanol 96:4); mp 54 -55°C; ¹ H NMR δ 0.88 (t, 6H, J = 6.6 Hz, 2 x Me), 1.20-1.35 (br s, 36H, 18 x CH ₂ ), 1.56 (pentet, 4H, J = 6.4 Hz, 2 OCH ₂ CH ₂ ), 2.69 (br s, 2H, OH), 3.42 (t, 4H, J = 6.5 Hz, dodecyl OCH ₂ ), 3.51 (s, 4H, OCH ₂ C), 3.64 (s, 4H, CH ₂ OH); ¹³ C NMR δ 73.3 (CCH ₂ OCH ₂ C), 72.2 (CH ₂ CH ₂ OC), 65.6 (CH ₂ OH), 44.6 (q C), 32.1 (CH ₂ CH ₂ CH ₃ ), 29.81 , 29.78, 29.77, 29.73, 29.58, 29.50 (6 dodecyl CH ₂ ), 26.3 (CH ₂ CH ₂ CH ₂ O), 29.66 (OCH ₂ CH ₂ ), 22.8 (CH ₂ CH ₃ ), 14.3 (Me). MS ESI: CaIc for C ₂₉ H ₆₁ O ₄ 473.46, found 473.3. Anal. CaIc. for C ₂₉ H ₆₀ O ₄ : C 73.67, H 12.79. Found: C 73.31 , H 12.68. Example 2D

2,2-Bis(tetradecyloxymethyl)-1 ,3-propanediol (2d)

H ₃ C(H ₂ C) ₁ H ₂ J ₁₃ CH ₃

[00112] Compound 1d (Example 1 D) (10.0 g, 16.2 mmol) is hydrogenated using the procedure of Example 2A in ethyl acetate (200 mL) containing 10% Pd/C (Degussa type, 0.5 g) to give a colourless solid that is recrystallized from ethyl acetate: yield 7.88 g, 92%; R _F 0.47 (dichloromethane: methanol 96:4); mp 63-64 ⁰ C; ¹ H NMR δ 0.88 (t, 6H, J = 6.6 Hz, 2 x Me), 1.20-1.35 (br s, 44H, 18 x CH ₂ ), 1.56 (pentet, 4H, J = 6.4 Hz, 2 OCH ₂ CH ₂ ), 2.83 (br s, 2H, OH), 3.42 (t, 4H, J = 6.5 Hz, dodecyl OCH ₂ ), 3.51 (s, 4H, OCH ₂ C), 3.64 (s, 4H, CH ₂ OH); ¹³ C NMR δ 73.4 (CCH ₂ OCH ₂ C), 72.2 (CH ₂ CH ₂ OC), 65.7 (CH ₂ OH), 44.6 (q C), 32.1 (CH ₂ CH ₂ CH ₃ ), 29.85, 2 x 29.83, 29.81 , 29.78, 29.75, 29.59, 29.51 (δ tetradecyl CH ₂ ), 29.65 (OCH ₂ CH ₂ ), 26.3 (CH ₂ CH ₂ CH ₂ O), 22.7 (CH ₂ CH ₃ ), 14.3 (Me); MS ESI: CaIc for C ₃₃ H ₆₉ O ₄ 529.52, found 529.3. Anal. CaIc. for C ₃₃ H ₆₈ O ₄ : C 74.94, H 12.96. Found: C 74.55, H 13.03.

Example 3A W,yV,yV',Λ/'-tetramethyl-5,5-bis(octyloxymethyl)-3,7-dioxa- 1,9-nonanediamine (3a)

[00113] Sodium hydride (15.71 g, 0.393 mol, 10 eq) is added slowly to a stirred solution of 2,2-bis(octyloxymethyl)-1 ,3-propanediol (2a, Example 2A) (14.15 g, 0.039 mol) in DMF (0.80 L) under nitrogen gas at 50 ⁰ C. The mixture is then vigorously stirred at 50 ⁰ C for 35 min. The reaction mixture is cooled to rt then 2-(dimethylamino)ethyl chloride hydrochloride (22.6 g, 0.157 mol, 4 eq) is added and washed into the stirring mixture with DMF (130 ml_). The reaction mixture is stirred at 50°C under N ₂ for 12 h, then quenched with methanol. The mixture is filtered and concentrated and the solid residue is dissolved in dichloromethane. The solution is washed with water (100 ml_), dried (MgSO ₄ ) and concentrated to an orange oil: yield 18.0 g, 91%; R _F on basic alumina 0.44 (chloroform: ethanol 98:2); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.25-1.33 (br m, 2OH, 10 x CH ₂ ), 1.51 (pentet, 4H, J = 6.8 Hz, 2 x OCH ₂ CH ₂ ), 2.26 (s, 12H, 2 x N(CH ₃ ) ₂ ), 2.49 (t, 4H, J = 5.8 Hz, OCH ₂ CH ₂ N), 3.35 (t, 4H, J = 6.5 Hz, decyl OCH ₂ ),), 3.36 (s, 4H, OCH ₂ C), 3.39 (s, 4H, OCH ₂ C), 3.49 (t, 4H, J = 6.0 Hz , OCH ₂ CH ₂ N); ¹³ C NMR δ 71.9 (CH ₂ CH ₂ OC), 70.5 (NCH ₂ CH ₂ OCH ₂ ), 70.3 (OCH ₂ CH ₂ N), 69.8 (CCH ₂ OCH ₂ CH ₂ C), 58.8 (OCH ₂ CH ₂ N), 46.1 (N(CH ₃ ) ₂ ), 45.6 (q C), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.70, 29.57, 29.54 (3 octyl CH ₂ ), 29.40 (OCH ₂ CH ₂ ), 26.3 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.2 (Me); ESI MS m/z calc for C ₂₉ H ₆₃ N ₂ O ₄ (M+1) 503.47, found 503.4; calc for M+Na 425.46, found 525.5. Example 3B 5,5-bis(decyloxymethyl)-Λ/,/V,Λ/',/V'-tetramethyl-3,7-diox a-1,9-nonanediamine (3b)

H

3b

[00114] Sodium hydride (10.99 g, 0.183 mol, 10 eq) is added slowly to a stirred solution of 2,2-bis(decyloxymethyl)-1 ,3-propanediol (2b, Example 2B) (9.5 g, 0.023 mol) in DMF (1 L) under nitrogen gas at 50 ⁰ C. The mixture is then vigorously stirred at 50 ⁰ C for 35 min. The reaction mixture is cooled to rt then 2-(dimethylamino)ethyl chloride hydrochloride (13.2 g, 0.092 mol, 4 eq) is added and washed into the stirring mixture with DMF (130 mL). The reaction mixture is stirred at 5O ⁰ C under N ₂ for 12 h, then quenched with methanol. The mixture is filtered and concentrated. The solid is dissolved in dichloromethane, filtered and solvent is evaporated off giving an orange oil: yield 12 g, 93%, R _F on basic alumina 0.46 (chloroform : ethanol 98 : 2); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.8 Hz, 2 x Me), 1.26 (br s, 28H, 14 x CH ₂ ), 1.52 (pentet, 4H, J = 6.6 Hz, 2 OCH ₂ CH ₂ ), 2.27 (s, 12H, 2 x N(CH ₃ ) ₂ ) , 2.51 (t, 4H ₁ J = 5.8 Hz , OCH ₂ CH ₂ N), 3.35 (t, 4H, J = 6.5 Hz, decyl OCH ₂ ), 3.36 (s, 4H, CH ₂ CH ₂ CH ₂ OCH ₂ C), 3.39 (s, 4H,

NCH ₂ CH ₂ OCH ₂ C), 3.51 (t, 4H, J = 5.8 Hz, OCH ₂ CH ₂ N); ¹³ C NMR δ 71.6 (CH ₂ CH ₂ OC), 70.4 (NCH ₂ CH ₂ OCH ₂ ), 70.1 (OCH ₂ CH ₂ N), 69.8 (CCH ₂ OCH ₂ CH ₂ C), 58.7 (OCH ₂ CH ₂ N), 46.0 (N(CHa) ₂ ), 45.5 (q C), 32.1 (CH ₂ CH ₂ CH ₃ ), 29.81 , 29.79, 29.75, 29.73, 29.65 (5 decyl CH ₂ ), 29.48 (OCH ₂ CH ₂ ), 26.4 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.2 (Me); ESI MS m/z calc for C ₃₃ H ₇ iN ₂ O ₄ (M+1): 559.54; Found: 559.5; m/z calc for M+Na, 581.52, found 581.5. Example 3C 5,5-bis(dodecyloxymethyl)-Λ/,Λ/,Λ/',Λ/'-tetramethyl-3,7- dioxa-1,9-nonanediamine (3c)

H iCH ₃

[00115] Treatment of compound 2c (Example 2C) (14.04 g, 0.02983 mol) in DMF (1 L) 5 with sodium hydride (26.84 g, 0.4474 mol, 15 eq) and 2-(dimethylamino)ethyl chloride hydrochloride (16.87 g, 0.117 mol, 4 eq) following the procedure of Example 3A gives the title compound (3c) as a orange oil: yield 17.6 g, 98%, R _F on basic alumina 0.51 (chloroform : ethanol 98 : 2); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.26-1.29 (br s, 36H, 10 x CH ₂ ), 1.52 (pentet, 4H, J = 6.6 Hz, 2 x OCH ₂ CH ₂ ), 2.27 (s, 12H, 2 x

10 N(CH ₃ ) ₂ ) , 2.51 (t, 4H, J = 5.9 Hz , OCH ₂ CH ₂ N), 3.35 (t, 4H, J = 6.5 Hz, dodecyl OCH ₂ ), 3.36 (s, 4H, CH ₂ CH ₂ CH ₂ OCH ₂ C), 3.39 (s, 4H, NCH ₂ CH ₂ OCH ₂ C), 3.51 (t, 4H, J = 5.9 Hz, OCH ₂ CH ₂ N); ¹³ C NMR δ 71.6 (CH ₂ CH ₂ OC), 70.4 (NCH ₂ CH ₂ OCH ₂ C), 70.1 (OCH ₂ CH ₂ N), 69.8 (CCH ₂ OCH ₂ CH ₂ C), 58.8 (OCH ₂ CH ₂ N), 45.9 (N(CH ₃ ) ₂ ), 45.4 (q C), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.82, 29.80, 29.79, 29.78, 29.77, 29.65 (6 decylCH ₂ ), 29.48 (OCH ₂ CH ₂ ),

15 26.4 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.2 (Me); ESI MS m/z calc for C ₃₇ H ₇₉ N ₂ O ₄ (M+1 ) 615.60. Found 615.5. CaIc for M+Na, 637.59, found 637.6.

Example 3D

Λ/,Λ/,Λ/',Λ/'-tetramethyl-3,7-dioxa-5,5-bis(tetradecy loxymethyl)-1,9-nonanediamine (3d)

H ₃

20

[00116] Treatment of compound 2d (Example 2D) (3.2 g, 6.49 mmol) in DMF (300 ml.) with sodium hydride (3.894 g, 0.0649 mol, 10 eq) and 2-(dimethylamino)ethyl chloride hydrochloride (3.7 g, 0.026 mol, 4 eq) following the procedure of Example 3A gives the title compound (3d) as a orange oil: yield 3.63 g, 83%, R _F 0.04 (methanol); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.24-1.32 (br s, 44H, 22 x CH ₂ ), 1.52 (pentet, 4H, J = 6.8 Hz, 2 OCH ₂ CH ₂ ), 2.26 (s, 12H ₁ 2 x N(CH ₃ J ₂ ), 2.49 (t, 4H, J = 5.9 Hz ₁ OCH ₂ CH ₂ N), 3.35 (t, 4H, J = 6.5 Hz, tetradecyl OCH ₂ ), 3.36 (s, 4H, CH ₂ CH ₂ CH ₂ OCOCH ₂ C), 3.39 (s, 4H, NCH ₂ CH ₂ OCH ₂ C), 3.50 (t, 4H, J = 5.9 Hz, OCH ₂ CH ₂ N); ¹³ C NMR δ 71.7 (CH ₂ CH ₂ OC), 70.4 (NCH ₂ CH ₂ OCH ₂ C), 70.3 (OCH ₂ CH ₂ N), 69.8 (CCH ₂ OCH ₂ CH ₂ C), 58.9 (OCH ₂ CH ₂ N), 46.2 (2 x N(CH ₃ J ₂ ), 45.5 (q C), 32.1 (CH ₂ CH ₂ CH ₃ ), 3 x 29.85, 29.83, 29.82, 2 x 29.80, 29.68 (8 tetradecyl CH ₂ ), 29.51 (OCH ₂ CH ₂ ), 26.4 (CH ₂ CH ₂ CH ₂ O), 22.8

(CH ₂ CH ₃ ), 14.3 (Me); ESI MS m/fc calc for C ₄₁ H ₈₇ N ₂ O ₄ (M+1) 671.67. Found 671.6. CaIc for M+Na, 693.65, found 693.7.

Example 3E tø,Λ/, W, W-Tetramethyl-6,6-bis(octyloxymethyl)-4,8-dioxa-1 ,11 -undecanediamine (3e)

3e

[00117] Sodium hydride (1.33 g, 55.4 mmol) is added slowly to a stirred solution of 2,2- dioctyloxymethyl-1 ,3-propanediol (2a, Example 2A) (2.0 g, 5.5 mmol) in DMF (100 mL) under an N ₂ atmosphere at 50 ⁰ C. The mixture is then stirred at 8O ⁰ C for 1 h. The reaction mixture is allowed to cool to rt, 3-chloro-Λ/,Λ/-dimethyl-1-propanamine hydrochloride (1.93 g, 12.2 mmol) is added in portions and the reaction mixture is stirred at 80 ⁰ C under nitrogen for another 24 h, then quenched with methanol and filtered. The filtrate is concentrated, and the residue is taken up in ethyl acetate (50 mL). This solution is washed with water (2 x 20 mL) and brine (20 mL), then dried (Na ₂ SO ₄ ) and concentrated to a residue that is purified by flash column chromatography. Elution using a gradient of 10 to 15% methanol in dichloromethane gives compound 3e as a light brown liquid: yield 1.6 g (54%); R _F on basic alumina 0.6 (dichloromethane: methanol 93:7); ¹ H NMR (CDCI ₃ ) δ 0.88 (t, 6H, J = 6.5 Hz, 2 CH ₃ ), 1.26-1.35 (m, 20 H ₁ 10 x CH ₂ ), 1.52 (p, 4H, J = 7.0 Hz, 2 OCH ₂ CH ₂ ), 1.71 (p, 4H, J = 6.5 Hz, 2 NCH ₂ CH ₂ ), 2.22 (s, 12H, 2 N(CH ₃ ) ₂ ), 2.32 (t, 4H, J = 7.5 Hz, 2 NCH ₂ ), 3.34 (t, 4H, J = 6.5 Hz, 2 CH ₂ CH ₂ O), 3.35 (s, 4H, 2 OCH ₂ ), 3.37 (s, 4H, 2 OCH ₂ ), 3.41 (t, 4H, J = 6.5 Hz, OCH ₂ ); ¹³ C NMR (CDCI ₃ ) δ 71.7 (octyl CH ₂ O), 70.0 (OCH ₂ CH ₂ CH ₂ N), 69.85 (OCH ₂ C), 69.78 (OCH ₂ C), 57.0 (NCH ₂ ), 45.64 (N(CH ₃ J ₂ ), 45.59 (qC), 32.0 (CH ₃ CH ₂ CH ₂ ), 29.82, 29.63, 29.49 (3 octyl CH ₂ ), 28.2 (NCH ₂ CH ₂ ), 26.4 5 (OCH ₂ CH ₂ CH ₂ ), 22.9 (CH ₃ CH ₂ ), 14.2 (CH ₃ ); HR ESI MS m/z calcd for C ₃ IH ₆₇ N ₂ O ₄ (M+H) 531.5095, found 531.5087.

Example 3F

6,6-Bis(decyloxymethyl)-W,/V,Λr,ΛT-tetramethyl-4,8-diox a-1 ,11 -undecanediamine (3f)

3f

10 [00118] Sodium hydride (0.57 g, 24.0 mmol), 2,2-didecyloxymethyl-1 ,3-propanediol (2b, Example 2B) (1.0 g, 2.4 mmol) in DMF (100 ml.) and 3-chloro-Λ/,Λ/-dimethyl-1- propanamine hydrochloride (1.8 g, 12 mmol) are reacted following the procedure of Example 3E to give compound 3f as a light brown liquid: yield 0.7 g (50%); R _F on basic alumina 0.44 (dichloromethane: methanol 95:5); ¹ H NMR (CDCI ₃ ) δ 0.88 (t, 6H, J = 6.5

15 Hz, CH ₃ ), 1.28-1.32 (m, 28 H, 14 x CH ₂ ), 1.52 (p, 4H, J = 7.0 Hz, OCH ₂ CH ₂ ), 1.70 (p, 4H, J = 6.5 Hz, NCH ₂ CH ₂ ), 2.22 (s, 12H, 2 N(CH ₃ J ₂ ), 2.31 (t, 4H, J = 7.5 Hz, NCH ₂ ), 3.34 (t, 4H, J = 6.5 Hz, CH ₂ O), 3.35 (s, 4H, OCH ₂ ), 3.37 (s, 4H, OCH ₂ ), 3.40 (t, 4H, J = 6.5 Hz, OCH ₂ ); ¹³ C NMR (CDCI ₃ ) δ 71.7 (decyl CH ₂ O), 70.0 (OCH ₂ CH ₂ CH ₂ N), 69.9 (OCH ₂ C), 69.8 (OCH ₂ C), 57.0 (NCH ₂ ), 45.7 (N(CH ₃ ) ₂ ), 45.6 (qC), 32.1 (CH ₃ CH ₂ CH ₂ ), 29.85 (x2),

20 29.79, 29.70, 29.52 (5 decyl CH ₂ ), 28.20 (NCH ₂ CH ₂ ), 26.4 (OCH ₂ CH ₂ CH ₂ ), 22.9 (CH ₃ CH ₂ ), 14.3 (CH ₃ ); ESI MS m/z calcd for C ₃₅ H ₇₅ N ₂ O ₄ (M+H) 587.5712, found 587.5742. Example 3G

6,6-Bis(dodecyloxymethyl)-/V,/V ₎ W,/V-tetramethy!-4,8-dioxa-1,11-undecanediamine (3g)

5 [00119] Sodium hydride (1.0 g, 42 mmol), 2,2-didodecyloxymethyl-1 ,3-propanediol (2c, Example 2C) (2.0 g, 4.2 mmol), and 3-chloro-Λ/,Λ/-dimethyl-1-propanamine hydrochloride (2.60 g, 16.9 mmol) are reacted together following the procedure of Example 3E. The reaction mixture is stirred at 90 ⁰ C under N ₂ for another 36 h, then quenched with methanol, and filtered and worked up following the procedure of Example 3E to give 3g

10 as a light brown liquid: yield 1.4 g (51%); R _F on basic alumina 0.5 (dichloromethane: methanol 97:5); ¹ H NMR (CDCI ₃ ) δ 0.88 (t, 6H, J = 6.5 Hz, CH ₃ ), 1.24-1.38 (m, 36 H, 18 x CH ₂ ), 1.52 (pentet, 4H, J = 7.0 Hz, OCH ₂ CH ₂ ), 1.72 (pentet, 4H, J = 6.5 Hz, NCH ₂ CH ₂ ), 2.22 (s, 12H, N(CHs) ₂ ), 2.32 (t, 4H, J = 7.5, NCH ₂ ), 3.35 (t, 4H, J = 6.5 Hz, CH ₂ O), 3.36 ( s, 4H, OCH ₂ ), 3.37 (s, 4H, OCH ₂ ), 3.41 (t, 4H, J = 6.5 Hz, OCH ₂ ); ¹³ C NMR (CDCI ₃ ) δ

15 71.6 (dodecyl CH ₂ O), 69.9 (OCH ₂ CH ₂ CH ₂ N), 69.72 (OCH ₂ C), 69.67 (OCH ₂ C), 56.9 (NCH ₂ ), 45.5 (N(CHa) ₂ ), 45.5 (qC), 31.9 (CH ₃ CH ₂ CH ₂ ), 29.75 - 29.65 (5C), 29.56, 29.38 (7 dodecyl CH ₂ ), 28.0 (NCH ₂ CH ₂ ), 26.3 (OCH ₂ CH ₂ CH ₂ ), 22.7 (CH ₃ CH ₂ ), 14.1 (CH ₃ ); HR ESI MS m/z calcd for C ₃₉ H ₈₃ N ₂ O ₄ (M+H) 643.6347, found 643.6331.

Example 3H 0 W,N,JV,W-Tetramethyl-4,8-dioxa-6,6-bis(tetradecyloxymethyl)- 1 ,11- undecanediamine (3h)

3h

[00120] Sodium hydride (2.2 g, 95 mmol), 2,2-tetradecyloxymethyl-1 ,3-propanediol (2d,

Example 2D) (5.0 g, 9.4 mmol), and 3-chloro-Λ/,Λ/-dimethyl-1-propanamine hydrochloride (5 98 g, 37 9 mmol) are reacted and worked up, following the procedure of Example 3E, to give compound 3h as a light brown liquid yield 2 2 g (35%), R _F on basic alumina 0 50 (dichloromethane methanol 97 5), ¹ H NMR (CDCI ₃ ) δ 0 88 (t, 6H, J = 6 5 Hz, CH ₃ ), 1 22- 1 34 (m, 44 H, 22 x CH ₂ ), 1 52 (p, 4H, J = 6 5 Hz, OCH ₂ CH ₂ ), 1 71 (p, 4H, J = 6 5 Hz, NCH ₂ CH ₂ ), 2 23 (s, 12H, N(CH ₃ J ₂ ), 2 33 (t, 4H, J = 7 5, NCH ₂ ), 3 34 (t, 4H, J = 6 5 Hz, CH ₂ O), 3 35 (s, 4H, OCH ₂ ), 3 36 (s, 4H, OCH ₂ ), 3 41 (t, 4H, J = 6 5 Hz, OCH ₂ ), ¹³ C NMR (CDCI ₃ ) δ 71 7 (tetradecyl CH ₂ O), 70 O (OCH ₂ CH ₂ CH ₂ N), 69 9 (OCH ₂ C), 69 8 (OCH ₂ C), 57 O (NCH ₂ ), 45 7 N(CH ₃ ) ₂ 44 8 (qC), 32 1 (OCH ₂ CH ₂ ), 29 9 (NCH ₂ CH ₂ ), 29 72, 29 53, 28 14, 26 4 (decyl CH ₂ ), 22 9 (CH ₃ CH ₂ ), 14 3 (CH ₃ ), HR ESI MS m/z calcd for C ₄₃ H ₉₁ N ₂ O ₄ (M+H) 699 6973, found 699 6986

Example 4A

Λ/,Λ/,Λ/',Λ/'-tetramethyl-5,5-bis(octyloxymethyl)-3,7 -dioxa-1,9-nonanediaminium dichloride (4a)

H

4a [00121] Sodium hydride (3 36 g, O 14 mol, 10 eq) is added slowly to a stirred solution of 2,2-bιs(octyloxymethyl)-1 ,3-propanedιol (2a, Example 2A) (5 05 g, O 014 mol) in DMF (500 mL) under nitrogen gas at rt and the mixture is stirred vigorously for 1 h 2-(Dιmethylamιno)ethyl chloride hydrochloride (8 08 g, O 05 mol, 4 eq) is added and the reaction mixture is stirred at 50 ⁰ C under an N ₂ atmosphere for 12 h, then quenched with methanol The mixture is filtered and concentrated The residue is taken up in diethyl ether (50 mL) and the resulting solution is washed with brine (50 mL), dried (MgSO ₄ ) and concentrated at 30-35 ⁰ C to give Λ/,Λ/,Λ/',Λ/'-tetramethyl-5,5-bιs(octyloxymethyl)-3,7-d ιoxa- 1 ,9-nonanedιamιne (3a) as a orange oil The crude product is taken up in dichloromethane (50 mL) and the resulting solution is shaken with ice cold 2 M HCI (30 mL) The aqueous layer is diluted with brine and this solution is extracted with dichloromethane (5 x 30 mL) The combined organic layers are dried (MgSO ₄ ) and concentrated to give the title compound (4a) as a light yellow solid, that is crystallized from ethyl acetate and acetone to give colorless crystals yield 4 90 g, 61 %, mp 150- 152°C; R _F on basic alumina 0.47 (dichloromethane: ethanol 96 :4); ¹ H NMR δ 0.88 (t, 6H, J = 6.8 Hz, 2 x Me), 1.27 (brs, 20H ₁ 1O x CH ₂ ), 1.50 (pentet, 4H, J = 6.3 Hz, 2 OCH ₂ CH ₂ ), 2.92 (s, 12H, 2 x N(CH ₃ J ₂ ), 3.33 (t, 4H, J = 6.7 Hz, octyl OCH ₂ ), 3.34 (s over broad pattern, 8H, octylOCH ₂ C and OCH ₂ CH ₂ N), 3.51 (s, 4H, N(CH ₂ ) ₂ OCH ₂ C), 3.90 (XX ^' part of AA ^' XX ^' pattern, 4H ₁ OCH ₂ CH ₂ N), 12.0 (br s, 2H, NH); ¹³ C NMR δ 71.7 (CH ₂ CH ₂ OC), 70.6 (CCH ₂ O (CH ₂ J ₂ N) ₁ 69.5 (CCH ₂ O octyl), 65.8 (OCH ₂ CH ₂ N), 56.7 (NCH ₂ CH ₂ ), 45.1 (q C), 43.6 (N(CHs) ₂ ), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.7, 29.5, 29.3, (octyl CH ₂ ), 26.2 (CH ₂ CH ₂ CH ₂ O), 22.7 (CH ₂ CH ₃ ), 14.2 (Me); HR ESI MS m/z calcd for C ₂₉ H ₆₃ N ₂ O ₄ (M+H) 503.4788, found 503.4784. Example 4B

5,5-Bis(decyloxymethyl)-Λ/,Λ/,Λ/',Λ/'-tetramethyl-3,7 -dioxa-1,9-nonanediaminium dichloride (4b)

H

4b

[00122] Compound 2b (Example 2B) (5.03 g, 0.012 mol) in DMF (700 ml.) with sodium hydride (4.83 g, 0.12 mol, 10 eq) and 2-(dimethylamino)ethyl chloride hydrochloride (6.91 g, 0.05 mol, 4 eq), following the procedure of Example 4A, gives 5,5- bis(decyloxymethyl)-Λ/,Λ/,Λ/',Λ/'-tetramethyl-3,7-dioxa- 1,9-nonanediamine (3b) as a orange oil. Treatment with ice cold 2 M HCI (30 ml_), following the procedure of Example 4A, gives the title compound (4b) as a yellow crystalline solid, that is crystallized from ethyl acetate and acetone to give light yellow crystals: yield 5.0 g, 66 %; mp 154-155°C; R _F on basic alumina 0.52 (dichloromethane: ethanol 96 : 4); ¹ H NMR δ 0.88 (t, 6H, J = 6.9 Hz ₁ 2 x Me), 1.26 (brs, 28H, 14 x CH ₂ ), 1.50 (pentet, 4H, J = 6.4 Hz, 2 OCH ₂ CH ₂ ), 2.91 (S ₁ 12H ₁ 2 x N(CH ₃ ) ₂ ), 3.30 (br AA ^" part of AA-XX ^" pattern 4H, OCH ₂ CH ₂ N), 3.33 (t, 4H, J = 6.6 Hz, decyl OCH ₂ ), 3.34 (s, 4H, decylOCH ₂ C), 3.51 (s, 4H, N(CH ₂ ) ₂ OCH ₂ C), 3.90 (XX ^" part of AA ^" XX ^" pattern, 4H ₁ OCH ₂ CH ₂ N); 12.2 (br s, 2H, NH); ¹³ C NMR δ 71.8 (CH ₂ CH ₂ OC), 70.7 (CCH ₂ O(CH ₂ ) ₂ N), 69.5 (CCH ₂ Odecyl), 65.8 (OCH ₂ CH ₂ N), 56.8 (NCH ₂ CH ₂ ), 45.2 (q C), 43.7 (N(CH ₃ J ₂ ), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.73, 29.71 , 29.68, 29.57, (decyl CH ₂ ), 29.40 (OCH ₂ CH ₂ ), 26.3 (CH ₂ CH ₂ CH ₂ O), 22.7 (CH ₂ CH ₃ ), 14.2 (Me), HR ESI MS m/z calcd for C ₃₃ H ₇₁ N ₂ O ₄ (M+H) 559.5411, found 559.5411. Example 4C

5,5-Bis(dodecyloxymethyl)-Λ/,Λ/,Λ/',/V'-tetramethyl-3, 7-dioxa-1,9-nonanediaminium dichloride (4c)

[00123] Treatment of compound 2c (Example 2C) (5.040 g, 0.0106 mol) in DMF (700 ml_) with sodium hydride (4.26 g, 0.106 mol, 10 eq) and 2-(dimethylamino)ethyl chloride hydrochloride (6.10 g, 0.042 mol, 4 eq), following the procedure of Example 4A, gives 5,5-bis(dodecyloxymethyl)-Λ/,Λ/,Λ/',Λ/'-tetramethyl-3,7- dioxa-1 ,9-nonanediamine (3c) as a orange oil, that is taken up in dichloromethane (30 ml_). This solution is shaken with ice cold 2 M HCI (30 ml_) following the procedure of Example 4A to give a colorless crystalline solid that is recrystallized from ethyl acetate and acetone to give colorless crystals: yield 5.20 g, 71%; mp 145 ⁰ C; R _F on basic alumina 0.55 (dichloromethane: ethanol 96 :4); ¹ H NMR δ 0.88 (t, 6H, J = 6.8 Hz, 2 x Me), 1.26 (br s, 36H ₁ 10 x CH ₂ ), 1.50 (pentet, 4H, J = 6.3 Hz, 2 OCH ₂ CH ₂ ), 2.90 (s, 12H, 2 x N(CH ₃ ) ₂ ), 3.30 (AA ^' part of AA ^' XX ^' pattern, 4H, J _AX + J _AX = 9.3Hz OCH ₂ CH ₂ N ), 3.33 (t, 4H, J = 6.5 Hz, dodecyl OCH ₂ ), 3.34 (s, 4H, dodecylOCH ₂ C), 3.51 (s, 4H, N(CH ₂ ) ₂ OCH ₂ C), 3.90 (XX ^" part of AA ^' XX ^' pattern, 4H, J _AX + J _AX = 9.3 Hz OCH ₂ CH ₂ N); 12.2 (br s, 2H, NH); ¹³ C NMR δ 71.7 (CH ₂ CH ₂ OC), 70.6 (CCH ₂ O(CH ₂ ) ₂ N), 69.5 (CCH ₂ Ododecyl), 65.7 (OCH ₂ CH ₂ N), 56.7 (NCH ₂ CH ₂ ), 45.1 (q C), 43.6 (N(CH ₃ ) ₂ ), 31.9 (CH ₂ CH ₂ CH ₃ ), 29.7, 29.5, 29.4 (dodecyl CH ₂ ), 26.2 (CH ₂ CH ₂ CH ₂ O), 22.7 (CH ₂ CH ₃ ), 14.1 (Me), HR ESI MS m/z calcd for C ₃₇ H ₇₉ N ₂ O ₄ (M+H) 615.6040, found 615.6046. Example 4D

Λ/,Λ/,Λ/',Λ/'-Tetramethyl-3,7-dioxa-5,5-bis(tetradecy loxymethyl)-1,9-nonanediaminium dichloride (4d)

H ₃

4d

5 [00124] Treatment of compound 2d (Example 2D) (5.28 g, 0.01 mol) in DMF (700 mL) with sodium hydride (4.0 g, 0.10 mol, 10 eq) and 2-(dimethylamino)ethyl chloride hydrochloride (5.7 g, 0.040 mol, 4 eq), following the procedure of Example 4A, gives Λ/,Λ/,Λ/',Λ/'-tetramethyl-3,7-dioxa-5,5-bis(tetradecylox ymethyl)-1 ,9-nonanediamine (3d) as a orange oil. Treatment with ice cold 2 M HCI (30 mL), following the procedure of

10 Example 4A, gives the title compound (4d) as a colorless crystalline solid, that is recrystallized from ethyl acetate and acetone to give colorless crystals: yield 5.55 g, 75%; mp 148-150 ⁰ C; R _F on basic alumina 0.57 (dichloromethane: ethanol 96 :4); ¹ H NMR δ 0.88 (t, 6H, J = 6.9 Hz, 2 x Me), 1.26 (br s, 44H, 22 x CH ₂ ), 1.50 (pentet, 4H, J = 6.4 Hz, 2 OCH ₂ CH ₂ ), 2.93 (s, 12H, 2 x N(CH ₃ J ₂ ), 3.30 (br AA ^" part of AA ^" XX ^' pattern, 4H,

15 OCH ₂ CH ₂ N ), 3.33 (t, 4H, J = 6.5 Hz, tetradecyl OCH ₂ ), 3.34 (s, 4H, tetradecylOCH ₂ C), 3.51 (s, 4H, N(CH ₂ ) ₂ OCH ₂ C), 3.90 (XX ^" part of AA ^' XX ^' pattern, 4H, OCH ₂ CH ₂ N); 12.0 (br s, 2H, NH); ¹³ C NMR δ 71.7 (CH ₂ CH ₂ OC), 70.6 (CCH ₂ O(CH ₂ ) ₂ N), 69.4 (CCH ₂ O tetradecyl), 65.7 (OCH ₂ CH ₂ N), 56.7 (NCH ₂ CH ₂ ), 45.1 (q C), 43.6 (N(CH ₃ ) ₂ ), 31.9 (CH ₂ CH ₂ CH ₃ ), 29.7, 29.7, 29.5, (tetradecyl CH ₂ ), 26.2 (CH ₂ CH ₂ CH ₂ O), 22.7 (CH ₂ CH ₃ ),

20 14.1 (Me); HR ESI MS m/z calcd for C ₄ iH ₈₇ N ₂ O ₄ (M+H) 671.6666, found 671.6662.

Example 4E

W.yV _j /V.W -Tetraethyl-S.δ-bistoctyloxymethyO-SJ-dioxa-i.θ-nonanediam inium dihydrochloride (4e)

4e

5 [00125] Sodium hydride (6.10 g, 0.15 mol, 10 eq) is added slowly to a stirred solution of 2,2-dioctyloxymethyl-1 ,3-propanediol (2a, Example 2A) (5.50 g, 0.015 mol) in THF (500 mL) under N ₂ gas at rt. When foaming ceases, the mixture is stirred vigorously at 6O ⁰ C for 1 h. The reaction mixture is cooled to rt, then 2-bromo-Λ/,Λ/-diethylethylamine hydrobromide (15.95 g, 0.061 mol, 4.0 eq) is added. The reaction mixture is stirred at

10 60 ⁰ C under N ₂ gas for 12 h, then quenched with methanol. The reaction mixture is filtered and the filtrate concentrated to a syrupy residue. The residue is taken up in diethyl ether (5OmL) and the resulting solution is washed with brine (50 mL), dried (MgSO ₄ ) and concentrated at 30-35°C to give crude Λ/,Λ/,Λ/',Λ/'-tetraethyl-5,5- bis(octyloxymethyl)-3,7-dioxa-1 ,9-nonanediamine. The crude product is taken up in

15 dichloromethane (50 mL) and the resulting solution is shaken with ice cold 2 M HCI (30 mL). The aqueous layer is diluted with brine (20 mL) and this solution is extracted with dichloromethane (5 x 30 mL). The combined organic layers are dried (MgSO ₄ ) and concentrated to give the title compound 4e as a colorless solid, that is crystallized from ethyl acetate and acetone to give colorless granules: yield 7.20 g, 75 %; mp 155°C; R _F

20 0.5 (96:4 dichloromethane : ethanol ); ¹ H NMR δ 0.88 (t, 6H, J = 6.8 Hz, 2 x Me), 1.27 (brs, 2OH, 1O x CH ₂ ), 1.42 (t, 12H, J = 7.2 Hz, 4 x Me), 1.51 (pentet, 4H, J = 6.3 Hz, 2 OCH ₂ CH ₂ ), 3.21 (very br AB part of ABX ₃ pattern, 8H, NCH ₂ CH ₃ ), 3.26 (br t, 4H, NCH ₂ CH ₂ O), 3.31 (s, 4H, octyl OCH ₂ C), 3.33 (t, 4H, J = 6.6 Hz, octyl OCH ₂ ), 3.44 (s, 4H, N(CH ₂ ) ₂ OCH ₂ C), 3.91 (t, 4H, J = 4.3 Hz, OCH ₂ CH ₂ N); 12.0 (br s, 2H, NH); ¹³ C NMR δ

25 71.7 (CH ₂ CH ₂ OC), 70.6 (CCH ₂ O(CH ₂ ) ₂ N), 69.4 (CCH ₂ O octyl), 65.8 (OCH ₂ CH ₂ N), 50.9 (NCH ₂ CH ₂ ), 47.3 (NCH ₂ CH ₃ ), 45.1 (q C), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.6, 29.5, 29.3 (octyl CH ₂ ), 26.2 (CH ₂ CH ₂ CH ₂ O), 22.7 (CH ₂ CH ₃ ), 14.1 (Me), 8.8 (Me); HR ESI MS m/z calcd for C ₃₃ H ₇₂ N ₂ O ₄ ^ (M+2H/2) 280.2741 , found 280.2741. Example 4F

5,5-Bis(decyloxymethyl)-N,N,N',N'-tetraethyl-3,7-dioxa-1, 9-nonanediaminium dihydrochloride (4f)

4f

5 [00126] Sodium hydride (0.96 g, 0.024 mol, 10 eq) is added slowly to a stirred solution of 2,2-didecyloxymethyl-1 ,3-propanediol (2b, Example 2B) (1.0 g, 0.0024 mol) in THF (50 ml.) under nitrogen gas at room temperature. When foaming ceases, the mixture is stirred vigorously at 5O ⁰ C for 1 h. The reaction mixture is cooled to rt, then 2-bromo-Λ/,Λ/- diethylethylamine hydrobromide (2.5 g, 0.0096 mol, 4 eq) is added. The reaction mixture

10 is stirred at 6O ⁰ C under nitrogen gas for 12-18 h, then quenched with methanol. The reaction mixture is filtered and the filtrate concentrated to a syrupy residue. The residue is taken up in diethyl ether (15 ml.) and the resulting solution is washed with water (3 x 5 ml_), dried (MgSO ₄ ) and concentrated at 30-35°C to give crude 1 ,3-bis[2-(Λ/,/V- diethylamino)ethoxy]-2,2-bis(decyloxymethyl)propane. The crude product is taken up in

15 dichloromethane (10 mL) and the resulting solution is shaken with ice cold 2 M HCI (10 mL). The aqueous layer is diluted with brine (5 mL) and this solution is extracted with dichloromethane (5 x 10 mL). The combined organic layers are dried (MgSO ₄ ) and concentrated to give the title compound (4f) as a colourless solid, yield 0.92 g, that is crystallized from ethyl acetate and acetone to give colourless granules: yield 0.84 g,

20 51 %; mp 144°C; R _F 0.63 (96:4 dichloromethane : ethanol ); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.26 (brs, 28H, 14 x CH ₂ ), 1.42 (t, 12H, J = 7.3 Hz, 4 x Me), 1.51 (pentet, 4H, J = 6.4 Hz, 2 OCH ₂ CH ₂ ), 3.21 (very br AB part of ABX ₃ pattern, 8H, NCH ₂ CH ₃ ), 3.26 (br t, 4H, NCH ₂ CH ₂ O), 3.30 (s, 4H, decylOCH ₂ C), 3.33 (t, 4H, J = 6.6 Hz, decyl OCH ₂ ), 3.44 (s, 4H, N(CH ₂ ) ₂ OCH ₂ C), 3.92 (t, 4H, J = 4.6 Hz, OCH ₂ CH ₂ N);

25 12.05 (br S, 2H, NH); ¹³ C NMR δ 71.8 (CH ₂ CH ₂ OC), 70.7 (CCH ₂ O(CH ₂ ) ₂ N), 69.5

(CCH ₂ Odecyl), 65.9 (OCH ₂ CH ₂ N), 51.1 (NCH ₂ CH ₂ ), 47.4 (NCH ₂ CH ₃ ), 45.2 (q C), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.73, 29.70, 29.57 (decyl CH ₂ ), 29.40 (OCH ₂ CH ₂ ), 26.3 (CH ₂ CH ₂ CH ₂ O), 22.7 (CH ₂ CH ₃ ), 14.2 (Me), 8.8 (Me); HR ESI MS m/z calc for C ₃₇ H ₇₉ N ₂ O ₄ (M+H) 615.6040, found 615.6036. Example 4G δ.δ-BistdodecyloxymethyO-N.N.N'.N'-tetraethyl-SJ-dioxa-I.S -nonanediaminium dihydrochloride (4g)

[00127] Treatment of compound 2c (Example 2C) (9.38 g, 0.0198 mol) in THF (500 ml.) with sodium hydride (7.90 g, 0.198 mol, 10 eq) and 2-bromo-Λ/,Λ/-diethylethylamine hydrobromide (20.7 g, 0.079 mol, 4 eq), following the procedure of Example 4E, gives a crude product, 1 ,3-bis[2-(Λ/,Λ/-diethylamino)ethoxy]-2,2-bis(dodecyloxymet hyl)propane. This compound is taken up in dichloromethane (30 ml_) and the resulting solution is shaken with ice cold 2 M HCI (30 mL). The aqueous layer is diluted with brine (30 mL) and this solution is extracted with dichloromethane (5 x 30 mL), following the procedure of Example 4E, to give the title compound 4g as a colourless solid that is crystallized from ethyl acetate and acetone to give colourless granules: yield 10.4 g, 70.9%; mp 150 ⁰ C; R _F 0.65 (96:4 dichloromethane : ethanol); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.26 (brs, 36H, 18 x CH ₂ ), 1.42 (t, 12H, J = 7.3 Hz, 4 x Me), 1.51 (pentet, 4H, J = 6.4 Hz, 2 OCH ₂ CH ₂ ), 3.21 (very br AB part of ABX ₃ pattern, 8H, NCH ₂ CH ₃ ), 3.26 (br t, 4H, J = 4.4 Hz, NCH ₂ CH ₂ ), 3.30 (s, 4H, dodecylOCH ₂ C), 3.33 (t, 4H, J = 6.6 Hz, dodecyl OCH ₂ ), 3.44 (s, 4H, N(CH ₂ ) ₂ OCH ₂ C), 3.92 (t, 4H, J = 4.6 Hz, OCH ₂ CH ₂ ); 12.05 (br s, 2H, NH); ¹³ C NMR δ 71.9 (CH ₂ CH ₂ OC), 70.8 (CCH ₂ O(CH ₂ ) ₂ N), 69.5 (CCH ₂ Ododecyl), 66.9 (OCH ₂ CH ₂ N), 51.1 (NCH ₂ CH ₂ ), 47.4 (NCH ₂ CH ₃ ), 45.2 (q C), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.79, 29.63, 29.46 (dodecyl CH ₂ ), 26.3 (CH ₂ CH ₂ CH ₂ O), 22.9 (CH ₂ CH ₃ ), 14.2 (Me), 8.8 (Me); HR ESI MS m/z calc for C ₄ iH ₈₇ N ₂ O ₄ (M+H) 671.6666, found 671.6669. Example 4H

/V,Λ/ _J Λ/',Λ/ -Tetraethyl-3,7-dioxa-5,5-bis(tetradecyloxymethyl)-1,9-nonan ediaminium dihydrochloride (4h)

4h

5 [00128] Treatment of compound 2d (Example 2D) (10.0g, 0.0189 mol) in THF (500 ml_) with sodium hydride (7.57 g, 0.189 mol, 10 eq) and 2-bromo-Λ/,Λ/-diethyIethylamine hydrobromide (19.7 g, 0.076 mol, 4 eq), following the procedure of Example 4E, gives a crude light yellow syrup, 1 ,3-bis[2-(Λ/,Λ/-diethylammonio)ethoxy]-2,2- bis(tetradecyloxymethyl)propane. The syrup is taken up in dichloromethane (50 mL) and

10 the solution is shaken with ice cold 2 M HCI (50 mL) following the procedure of Example 4E, to give a colourless solid that is crystallized from ethyl acetate and acetone to give colourless granules: yield 11.5 g, 76.2%; mp 146°C; R _F 0.69 ( 96:4 dichloromethane : ethanol ); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz ₁ 2 x Me), 1.26 (brs, 44H, 22 x CH ₂ ), 1.41 (t, 12H, J = 7.2 Hz, 4 x Me), 1.51 (pentet, 4H, J = 6.4 Hz, 2 OCH ₂ CH ₂ ), 3.20 (very br AB

15 part of ABX ₃ pattern, 8H, NCH ₂ CH ₃ ), 3.24 (br t, NCH ₂ CH ₂ ), 3.30 (s, 4H, tetradecylOCH ₂ C), 3.33 ( t, 4H, J = 6.6 Hz, tetradecyl OCH ₂ ), 3.44 (s, 4H, N(CH ₂ ) ₂ OCH ₂ C), 3.91 (t, 4H, J = 4.5 Hz, OCH ₂ CH ₂ N), 12.05 (brs, 2H, NH); ¹³ C NMR δ 71.8 (CH ₂ CH ₂ OC), 70.8 (CCH ₂ O(CH ₂ ) ₂ N), 69.5 (CCH ₂ Otetradecyl), 66.1 (OCH ₂ CH ₂ N), 51.2 (NCH ₂ CH ₂ ), 47.2 (NCH ₂ CH ₃ ), 45.2 (q C), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.72, 29.77, 29.65,

20 29.47 (tetradecyl CH ₂ ), 26.4 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.2 (Me), 8.9 (Me); HR ESI MS m/z calc for C ₄₅ H ₉₅ N ₂ O ₄ (M+H) 727.7292, found 727.7293. Example 5A

1 ,3-Bis[2-(Λ/,Λ/,Λ/-trimethylammonio)ethoxy]-2,2-bis(octyl oxymethyl)propane diiodide (5a)

5a

5 Compound 3a (Example 3A) (7.49 g, 0.0149 mol) is shaken with methyl iodide (8.28 g, 0.0584 mol, 4 eq) for 2 min, then dichloromethane (100 ml_) is added and shaking is continued for 5 min. The reaction mixture is concentrated to a yellow solid that is washed with acetone, then crystallized from toluene : ethanol 10 : 1 to give colourless crystals: yield 10.17 g, 86.8 %; recrystallized from ethyl acetate: methanol; R _F on basic alumina

10 0.54 (butanol, water, methanol 4:1 : trace); mp softens 180 ⁰ C, melts 188 - 189 ⁰ C; ¹ H NMR δ 0.89 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.28 -1.32 (brs, 2OH, 1O x CH ₂ ), 1.51 (pentet, 4H, J = 6.3 Hz, 2 OCH ₂ CH ₂ ), 3.30 (s, 4H, OCH ₂ C), 3.33 (t, 4H, J = 6.6 Hz, octyl OCH ₂ ), 3.51 (s, 4H OCH ₂ C), 3.54 (s, 18H, 2 x N(CH ₃ ) ₃ ), 3.94 (br s, 4H, OCH ₂ ), 4.02 (br m, 4H, CH ₂ N); ¹³ C NMR δ 71.8 (CH ₂ CH ₂ OC), 70.9 (CCH ₂ OCH ₂ C), 69.4, (CCH ₂ OCH ₂ C),

15 65.8 (CH ₂ N), 65.4 (OCH ₂ CH ₂ N), 54.9 (N(CH ₃ J ₃ ), 45.2 (q C), 31.9 (CH ₂ CH ₂ CH ₃ ), 29.66, 29.41 , 29.32 (3 octyl CH ₂ ), 29.46 (OCH ₂ CH ₂ ), 26.2 (CH ₂ CH ₂ CH ₂ O), 22.7 (CH ₂ CH ₃ ), 14.2 (Me); ESI MS m/z calc for C ₃₁ H ₆₈ N ₂ O ₄ I: 659.45, found 659.1(M-I). Anal. CaIc for C ₃₁ H ₆₈ N ₂ O ₄ I ₂ : C 47.33, H 8.71 , N 3.56. Found: C 47.34, H 8.51 , N 3.29.

Example 5B

1,3-Bis[2-(W,/V,/V-trimethylammonio)ethoxy]-2,2-bis(decyl oxymethyl)propane diiodide (5b)

5b

5 Compound 3b (Example 3B) (11.0 g, 0.0197 mol) is shaken with methyl iodide (4.91 ml_, 11.2 g, 0.0716 mol, 4 eq) for 2 min, then dichloromethane (250 mL) is added and shaking is continued for 5 min. The reaction mixture is concentrated to a solid that is crystallized from toluene: ethanol 10:1 to give colorless crystals: yield 16 g, 96%, that are recrystallized from ethyl acetate-methanol to give colorless translucent cubes: R _F on

10 basic alumina 0.59 (butanol, water, methanol 4:1 : trace); mp 100-110 ⁰ C becomes opaque, 180 - 183°C, clears, 186 ⁰ C, melts; ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.27 -1.31 (brs, 28H, 14 x CH ₂ ), 1.50 (pentet, 4H, J = 6.3 Hz, 2 OCH ₂ CH ₂ ), 3.29 (s, 4H, OCH ₂ C) , 3.33 (t, 4H, J = 6.6 Hz, decyl OCH ₂ ), 3.51 (s, 4H OCH ₂ C), 3.53 (s, 18H, 2 x N(CHs) ₃ ), 3.94 (br s, 4H, OCH ₂ ), 4.02 (br m, 4H, CH ₂ N); ¹³ C NMR δ 71.8 (CH ₂ CH ₂ OC),

15 70.9 (CCH ₂ OCH ₂ C), 69.4 (CCH ₂ OCH ₂ C), 65.8 (CH ₂ N(CHs) ₃ ), 65.4 (OCH ₂ CH ₂ N), 54.9 (N(CHa) ₃ ), 45.1 (q C), 31.9 (CH ₂ CH ₂ CH ₃ ), 29.65, 29.63, 29.60, 29.41 (5 decyl CH ₂ ), 29.49 (OCH ₂ CH ₂ ), 26.2 (CH ₂ CH ₂ CH ₂ O), 22.7 (CH ₂ CH ₃ ), 14.1 (Me); ESI MS m/z calc for C ₃₅ H ₇₇ N ₂ O ₄ I: 715.52, found 715.3 (M-I). Anal. CaIc for C ₃₅ H ₇₆ N ₂ O ₄ I ₂ , 49.88, H 9.09, N 3.32. Found: C 49.84, H 9.16, N 3.14.

Example 5C

1,3-Bis[2-(N,N,N-trimethylammonio)ethoxy]-2,2-bis(dodecyl oxymethyl)propane diiodide (5c)

5c

5 [00129] Treatment of compound 3c (Example 3C) (17.6 g, 0.0286 mol) with methyl iodide (7.14 mL, 16.2 g, 0.114 mol, 4 eq) following the procedure of Example 5A gives the title compound (5c) as colorless crystals: yield 21.44 g, 84.8 %; recrystallized from ethyl acetate - methanol to give colorless needles: R _F on basic alumina 0.62 (butanol, water, methanol 4: 1 : trace) ; mp 100-115 ⁰ C becomes opaque, 155 - 18O ⁰ C, clears,

10 183°C, melts; ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.26 - 1.31 (br s, 36H, 18 x CH ₂ ), 1.50 (pentet, 4H, J = 6.3 Hz, 2 OCH ₂ CH ₂ ), 3.29 (s, 4H, OCH ₂ C), 3.33 (t, 4H, J = 6.6 Hz, dodecyl OCH ₂ ), 3.53 (s, 18H, 2 x N(CH ₃ J ₃ ), 3.51 (s, 4H, OCH ₂ C), 3.94 (br s, 4H ₁ OCH ₂ ), 4.02 (br m, 4H, 2 x CH ₂ N(CH ₃ ) ₃ ); ¹³ C NMR δ 71.8 (CH ₂ CH ₂ OC), 70.9 (CH ₂ OCH ₂ C), 69.4 (CCH ₂ OCH ₂ C), 65.9 (CH ₂ N), 65.4 (OCH ₂ CH ₂ N), 55.0 (N(CH ₃ ) ₃ ), 45.2

15 (q C), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.75, 29.75, 29.72, 29.41 (7 dodecyl CH ₂ ), 29.58 (OCH ₂ CH ₂ ), 26.3 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.2 (Me); ESI MS CaIC fOr C ₃₉ H ₈₄ N ₂ O ₄ I 771.58, found 771.3 (M-I). Anal. CaIc. for C ₃₉ H ₈₄ N ₂ O ₄ I ₂ : C 52.11 , H 9.42, N 3.12. Found: C 52.11 , H 9.24, N 2.99.

Example 5D

1,3-Bis[2-(N,N,N-trimethylammonio)ethoxy]-2,2-bis(tetrade cyloxymethyl)propane diiodide (5d)

5d

5 [00130] Treatment of compound 3d (Example 3D) (3.63 g, 0.00570 mol) with methyl iodide (1.42 mL, 3.236 g, 0.0228 mol, 4 eq) following the procedure of Example 5A gives the title compound (5d) as colorless crystals: yield 3.7 g, 69 %; recrystallized from ethyl acetate-methanol as opaque colorless crystals; R _F on basic alumina 0.65 (butanol, water, methanol 4:1 : trace); mp, 160 - 180 ⁰ C, becomes transparent, 185°C, melts; ¹ H

10 NMR δ 0.88 ppm (t, 6H ₁ J = 6.9 Hz, 2 x Me), 1.26 -1.31 (brs, 44H ₁ 22 x CH ₂ ), 1.50 (pentet, 4H, J = 6.3 Hz, 2 OCH ₂ CH ₂ ), 3.29 (s, 4H, 2 x OCH ₂ C), 3.33 (t, 4H, J = 6.6 Hz, tetradecyl OCH ₂ ), 3.52 (s, 4H, 2 x OCH ₂ C), 3.53 (s, 18H, 2 x N(CH ₃ J ₃ ), 3.93 (br s, 4H, 2 x OCH ₂ CH ₂ N), 4.02 (br m, 4H, 2 x CH ₂ N); ¹³ C NMR δ 71.9 (CH ₂ CH ₂ OC), 70.9 (CCH ₂ OCH ₂ C), 69.4 (CCH ₂ OCH ₂ C), 65.8 (CH ₂ N), 65.5 (OCH ₂ CH ₂ N), 54.9 (N(CH ₃ ) ₃ ),

15 45.2 (q C), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.81 , 29.75, 29.64, 29.41 (9 tetradecyl CH ₂ ), 29.45 (OCH ₂ CH ₂ ), 26.3 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.2 (Me); ESI MS m/z calc for C ₄₃ H ₉₁ N ₂ O ₄ I: 827.59, found 827.3 (M-I). Anal. CaIc for C ₄₃ H ₉₂ N ₂ O ₄ I ₂ : C 54.08, H 9.71 , N 2.93. Found: C 54.16, H 9.53, N 2.83.

Example 5E

Λ/,/V,/V,/V',yV',Λ/'-Hexaethyl-5,5-bis(octyloxymethyl)- 3,7-dioxa-1,9- nonanediammonium dibromide (5e)

5e

5 [00131] Salt 4e (Example 4E) (1.44g, 2.28 mmol) is dissolved in a NaOH solution (2 M, 15 mL). The resulting mixture is extracted with diethyl ether (3 x 5 ml.) to yield a colorless syrup of Λ/,Λ/,Λ/',Λ/'-tetraethyl-5,5-bis(octyloxymethyl)-3,7-dio xa-1 ,9- nonanediamine, yield 1.08 g, 85 %; R _F 0.43 on basic alumina (dichloromethane : ethanol, 98:2); ¹ H NMR δ 0.88 (t, 6H, J = 6.8 Hz, 2 x Me), 1.03 (t, J = 7.2 Hz, 12H, 4 x Me ) 1.28

10 (br s, 2OH, 10 x CH ₂ ), 1.51 (pentet , 4H, J = 6.8 Hz, 2 OCH ₂ CH ₂ ), 2.57 (q, 8H, J = 7.1 Hz, 2 x N(CH ₂ CHa) ₂ ), 2.65 (t , 4H, J = 6.2 Hz, 2NCH ₂ CH ₂ ) , 3.35 (t, J = 6.5 Hz, 4H, octyl OCH ₂ ), 3.35 (s, 4H, decylOCH ₂ C), 3.38 (s, 4H, CCH ₂ O(CH ₂ ) ₂ N), 3.47 (t, J = 6.3 Hz, 4H, 2 OCH ₂ CH ₂ ); ¹³ C NMR δ 71.6 (CH ₂ CH ₂ OC), 70.4 (CCH ₂ O(CH ₂ ) ₂ N), 70.4 (CH ₂ CH ₂ N), 69.8 (CCH ₂ O octyl), 52.1 (NCH ₂ CH ₂ ), 47.8 (NCH ₂ CH ₃ ), 45.4 (q C), 32.0 (CH ₂ CH ₂ CH ₃ ),

15 29.8, 29.6, 29.5, 29.3 (octyl CH ₂ ), 26.3 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.2 (Me), 12.1 (CH ₂ CH ₃ ).

[00132] Ethyl bromide (98%, 2.78 mL, 37.3 mmol, 20.0 eq) is added to a stirred solution of Λ/,Λ/,Λ/',Λ/'-tetraethyl-5,5-bis(octyloxymethyl)-3,7-dio xa-1 ,9-nonanediamine (1.04 g, 1.86 mmol) in a mixture of THF and ethanol (6 mL) (2:1). Potassium carbonate (0.5 g, 0 3.7 mmol, 2 eq) is added and the resulting mixture is refluxed for 26 h, then cooled to rt, filtered, and the filtrate is concentrated to give the title compound (5e) as a colorless sticky solid (1.92 g). The salt precipitated from ethyl acetate containing a few drops of methanol, yield 1.13 g, 78 %; mp 157°C; R _F 0.53 on basic alumina (butanol: water: methanol 20: 5: 2); ¹ H NMR δ 0.88 (t, 6H, J = 6.9 Hz, 2 x Me), 1.28 (br s, 2OH, 1O x CH ₂ ), 5 1.41 (t, J = 7.2 Hz, 12H, 6 x Me), 1.51 (pentet , 4H, J = 6.5 Hz, 2 OCH ₂ CH ₂ ), 3.28 (s, 4H, octylOCH ₂ C), 3.33 (t, J = 6.6 Hz, 4H, octyl OCH ₂ ), 3.47 (s, 4H, CCH ₂ O(CH ₂ ) ₂ N), 3.4 7 (q, 12H, J = 7.2 Hz, 2 N (CH ₂ CH ₃ ) ₂ ), 3.79 (AA ^" part of AA ^' BB' pattern, 4H, 2 NCH ₂ CH ₂ ), 3.94 (BB ^' part of AA BB ^' pattern, 4H, 2OCH ₂ CH ₂ ); ¹³ C NMR δ 71.9 (CH ₂ CH ₂ OC), 71.1 (CCH ₂ O(CH ₂ ) ₂ N), 69.5 (CCH ₂ O octyl), 65.1 (OCH ₂ CH ₂ N), 57.8 (NCH ₂ CH ₂ ), 54.4 (NCH ₂ CH ₃ ), 45.3 (q C), 31.9 (CH ₂ CH ₂ CH ₃ ), 29.7, 29.6 , 29.4, (octyl CH ₂ ), 26.3 (CH ₂ CH ₂ CH ₂ O), 22.7 (CH ₂ CH ₃ ), 14.2 (Me), 8.4 (CH ₂ CH ₃ ); HR ESI MS m/z calcd for C ₃₇ H ₈₀ N ₂ O ₄ ^ (M-2Br)/2 308.3054, found 308.3038.

5 Example 5F

S.δ-BistdecyloxymethyO-N.N.N.N'.N'.N'-hexaethyl-SJ-dioxa -i.θ- nonanediammonium dibromide (βf)

5f

[00133] Salt 4f (Example 4F) (0.87 g, 1.18 mmol) is dissolved in a NaOH solution (2 M, 10 10 mL). The resulting mixture is extracted with dichloromethane (3 x 5 ml.) to yield a colourless syrup of 5,5-bis(decyloxymethyl)-Λ/,Λ/,Λ/',/V'-tetraethyl-3,7-diox a-1 ,9- nonanediamine, yield 0.69 g, 95.8 %; R _F 0.44 on basic alumina (dichloromethane : ethanol, 98:2); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.03 (t, J = 7.2 Hz, 12H, 4 x Me ) 1.26 (br s, 28H, 14 x CH ₂ ), 1.52 (pentet , 4H, J = 6.7 Hz, 2 OCH ₂ CH ₂ ), 2.57 (q, 15 8H, J = 7.14 Hz, 2 x N(CH ₂ CH ₃ ),), 2.65 (t , 4H, J = 6.2 Hz, 2NCH ₂ CH ₂ ) , 3.35 (t, J = 6.5 Hz, 4H, decyl OCH ₂ ), 3.35 (s, 4H, decylOCH ₂ C), 3.38 (s, 4H, CCH ₂ O(CH ₂ ) ₂ N), 3.47 (t, J = 6.2 Hz, 4H, 2 OCH ₂ CH ₂ ); ¹³ C NMR δ 71.7 (CH ₂ CH ₂ OC), 70.4 (CCH ₂ O(CH ₂ ) ₂ N), 70.4 (CH ₂ CH ₂ N), 69.8 (CCH ₂ Odecyl), 52.2 (NCH ₂ CH ₂ ), 47.6 (NCH ₂ CH ₃ ), 45.3 (q C), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.7, 29.6, 29.5, 29.3 (decyl CH ₂ ), 26.2 (CH ₂ CH ₂ CH ₂ O), 22.6 (CH ₂ CH ₃ ), 20 14.0 (Me), 11.90 (CH ₂ CH ₃ ).

[00134] Ethyl bromide, 98% (1.71 mL, 22.5 mmol, 20.0 eq) is added to a stirred solution of 5,5-bis(decyloxymethyl)-Λ/,Λ/,Λ/',Λ/'-tetraethyl-3,7-dio xa-1 ,9-nonanediamine (0.69 g, 1.12 mmol) in a mixture of THF and ethanol (6 mL) (2:1). Potassium carbonate (0.13 g, 2.24 mmol, 2.0 eq) is added and the resulting mixture is refluxed for 26 h, then cooled to 25 rt, filtered, and the filtrate is concentrated to give the title compound (5f) as a colourless crystalline solid, yield 0.78 g, 86%; R _F on basic alumina 0.40 (butanol, water, methanol 4:1 : trace); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.27 (br s, 28H, 14 x CH ₂ ), 1.40 (t, J = 7.2 Hz, 12H, 6 x Me ) 1.51 (pentet , 4H, J = 6.3 Hz, 2 OCH ₂ CH ₂ ), 3.28 (s, 4H, decylOCH ₂ C), 3.33 (t, J = 6.6 Hz, 4H, decyl OCH ₂ ), 3.46 (s, 4H, CCH ₂ O(CH ₂ ) ₂ N), 3.57 (q, 12H, J = 7.2 Hz, 2 N (CH ₂ CH ₃ ) ₂ ), 3.78 (AA ^" part of AA ^' BB ^" pattern, 4H, 2 NCH ₂ CH ₂ ), 3.90 (BB ^' part of AAΕB ^" pattern, 4H, 2OCH ₂ CH ₂ ); ¹³ C NMR δ 71.7 (CH ₂ CH ₂ OC), 70.9 (CCH ₂ O(CH ₂ ) ₂ N), 69.3 (CCH ₂ Odecyl), 64.8 (OCH ₂ CH ₂ N), 57.5 (NCH ₂ CH ₂ ), 54.2 (NCH ₂ CH ₃ ), 45.0 (q C), 31.8 (CH ₂ CH ₂ CH ₃ ), 29.5, 29.5 , 29.5, 29.4, 29.2 (decyl CH ₂ ), 26.1 (CH ₂ CH ₂ CH ₂ O), 22.5 (CH ₂ CH ₃ ), 14.0 (Me), 8.2 (CH ₂ CH ₃ ). HR ESI MS m/z calc for C _4I H ₈₈ BrN ₂ O ₄ (M+Br): 751.5927. Found: 751.5925.

Example 5G β.δ-BistdodecyloxymethyO-N.N.N^'.N'.N'-hexaethyl-SJ-dioxa- i^- nonanediammonium dibromide (5g)

1 CHs

5g

[00135] Salt 4g (Example 4G) (5.5 g, 7.4 mmol) is dissolved in a NaOH solution (2 M, 30 ml_). The resulting mixture is extracted with diethyl ether (2 x 25 mL) to yield a colourless syrup of 5,5-bis(dodecyloxymethyl)-Λ/,Λ/,Λ/',Λ/'-tetraethyl-3,7-d ioxa-1 ,9- nonanediamine, yield 4.66 g, 94.1%; R _F 0.46 on basic alumina (dichloromethane : ethanol, 98:2), ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.03 (t, J = 7.14 Hz, 12H, 4 x Me ) 1.27 (brs, 36H, 18 x CH ₂ ), 1.52 (pentet, 4H, J = 6.6 Hz, 2 OCH ₂ CW ₂ ), 2.58 (q, 8H, J = 7.1 Hz, 2 x N(CH ₂ CHs) ₂ ), 2.67 (t, 4H, J = 6.1 Hz, 2 NCH ₂ CH ₂ ) , 3.35 (t, J = 6.6 Hz, 4H, dodecyl OCH ₂ ), 3.35 (s, 4H, dodecylOCH ₂ C), 3.39 (s, 4H, CCH ₂ O(CH ₂ ) ₂ N), 3.48 (t, J = 6.1 Hz, 4H, 2 OCH ₂ CH ₂ N); ¹³ C NMR δ 71.3 (CH ₂ CH ₂ OC), 70.0 (CCH ₂ O(CH ₂ ) ₂ N), 70.0 (OCH ₂ CH ₂ N), 69.5 (CCH ₂ Ododecyl), 51.9 (NCH ₂ CH ₂ ), 47.5 (NCH ₂ CH ₃ ), 45.2 (q C), 31.9 (CH ₂ CH ₂ CH ₃ ), 29.5, 29.4, 29.2 (dodecyl CH ₂ ), 26.1 (CH ₂ CH ₂ CH ₂ O) ₁ 22.5 (CH ₂ CH ₃ ), 13.9 (Me), 11.8 (CH ₂ CH ₃ ).

[00136] Ethyl bromide (21.0 mL, 276 mmol, 40.0 eq) is added to a stirred solution of 5,5-bis(dodecyloxymethyl)-Λ/,Λ/,Λ/',Λ/'-tetraethyl-3,7-d ioxa-1 ,9-nonanediamine (4.66 g, 6.96 mmol) in a mixture of THF and ethanol (3:2) (50 mL). Potassium carbonate (2.37 g, 17.2 mmol, 2.5 eq) is added and the resulting mixture is refluxed for 33 h, cooled to rt, filtered, and the filtrate is concentrated to give the title compound (5g) as a colourless solid. Crystallization from ethyl acetate and acetone gives colourless granules: yield 4.79 g, 78.4%; mp 185°C; R _F on basic alumina 0.42 (butanol, water, methanol 4:1 : trace); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.8 Hz, 2 x Me), 1.27 (brs, 36H, 18 x CH ₂ ), 1.41 (t, J = 7.2 Hz, 12H, 6 x Me), 1.51 (pentet, 4H, J = 6.3 Hz, 2 OCH ₂ CH ₂ ), 3.27 (s, 4H, dodecylOCH ₂ C), 3.32 (t, J = 6.6 Hz, 4H, dodecyl OCH ₂ ), 3.48 (s, 4H, CCH ₂ O(CH ₂ ) ₂ N), 3.58 (q, 12H, J = 7.2 Hz, 2 N (CH ₂ CH ₃ ) ₂ ), 3.81 (AA ^" part of AA ^" BB ^' pattern, 4H, 2 NCH ₂ CH ₂ O), 3.95 (BB ^' part of AA ^' BB ^' pattern, 4H, 2 OCH ₂ CH ₂ N); ¹³ C NMR δ 71.8 (CH ₂ CH ₂ OC), 71.0 (CCH ₂ O(CH ₂ ) ₂ N), 69.5 (CCH ₂ Ododecyl), 64.9 (OCH ₂ CH ₂ N), 57.6 (NCH ₂ CH ₂ O), 54.3 (NCH ₂ CH ₃ ), 45.2 (q C), 31.9 (CH ₂ CH ₂ CH ₃ ), 29.7, 29.7, 29.6, 29.4 (dodecyl CH ₂ ), 26.3 (CH ₂ CH ₂ CH ₂ O), 22.7 (CH ₂ CH ₃ ), 14.1 (Me), 8.3 (CH ₂ CH ₃ ). HR ESI MS m/z calc for C ₄₅ H ₉₆ BrN ₂ O ₄ (M+Br): 807.6553. Found: 807.6549

Example 5H

N,N,N,N',N',N'-Hexaethyl-3,7-dioxa-5,5-bis(tetradecyloxym ethyl)-1,9- nonanediammonium dibromide (5h)

5h

[00137] Salt 4h (Example 4H) (5.42g, 6.79 mmol) is dissolved in a 2 M NaOH solution (30 ml_). The resulting mixture is extracted with diethyl ether (2 x 25 mL) to yield a colourless syrup of Λ/,Λ/,Λ/',Λ/'-tetraethyl-5,5-bis(tetradecyloxymethyl)-3, 7-dioxa-1 ,9- nonanediamine: yield 4.11 g, 83.9%; R _F 0.48 on basic alumina (dichloromethane : ethanol 98:2), ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.02 (t, 12H, J = 7.1 Hz, 4 x Me), 1.28 (brs, 44H, 22 x CH ₂ ), 1.52 (pentet, 4H, J = 6.8 Hz, 2 OCH ₂ CH ₂ ), 2.57 (q, 8H, J = 7.1 Hz, 2 N(CH ₂ CHa) ₂ ), 2.65 (t , 4H, J = 6.2 Hz, 2 NCH ₂ CH ₂ ), 3.35 (t, J = 6.5 Hz, 4H, tetradecyl OCH ₂ ), 3.35 (s, 4H, tetradecylOCH ₂ C), 3.39 (s, 4H, CCH ₂ O(CH ₂ ) ₂ N), 3.48 (t, J = 6.3 Hz, 4H, 2 OCH ₂ CH ₂ ); ¹³ C NMR δ 71.5 (CH ₂ CH ₂ OC), 70.4 (CCH ₂ O(CH ₂ ) ₂ N), 70.3 (OCH ₂ CH ₂ N), 69.7 (CCH ₂ Otetradecyl), 52.1 (NCH ₂ CH ₂ ), 47.8 (NCH ₂ CH ₃ ), 45.4 (q C), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.8, 29.7, 29.6, 29.4 (tetradecyl CH ₂ ), 26.3 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.1 (Me), 12.1 (CH ₂ CH ₃ ).

[00138] Treatment of a mixture of ethyl bromide (16.9 mL, 224 mmol, 40.0 eq) and Λ/,Λ/,Λ/',Λ/'-tetraethyl-5,5-bis(tetradecyloxymethyl)-3, 7-dioxa-1 ,9-nonanediamine (4.1 1 g, 5.66 mmol) in a THF ethanol solution (3:2) (50 ml_) containing potassium carbonate (1.95 g, 14.2 mmol, 2.5 eq) as above gives the title compound (5h), as colourless solid. It is recrystallized from ethyl acetate and acetone to give colourless granules: yield 4.50 g, 85.4%; mp 180°C; R _F on basic alumina 0.43 (butanol, water, methanol 4:1 : trace); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.26 (brs, 44H, 22 x CH ₂ ), 1.41 (t, J = 7.2 Hz, 12H, 6 x Me ), 1.50 (pentet , 4H, J = 6.3 Hz, 2 x OCH ₂ CH ₂ ), 3.27 (s, 4H, 2 x tetradecylOCH ₂ C ), 3.32 (t, J = 6.6 Hz, 4H, decyl OCH ₂ ), 3.48 (s, 4H, CCH ₂ O(CH ₂ ) ₂ N), 3.58 (q, 12H, J = 7.2 Hz, 2 N(CH ₂ CH ₃ ) ₂ ), 3.81 (AA ^' part of an AAΕB ^' pattern, 4H, 2 NCH ₂ CH ₂ ), 3.95 (BB ^' part of AA ^' BB ^" pattern, 4H, 2 OCH ₂ CH ₂ ); ¹³ C NMR δ 71.7

(CH ₂ CH ₂ OC), 70.9 (CCH ₂ O(CHz) ₂ N), 69.4 (CCH ₂ Otetradecyl), 64.9 (OCH ₂ CH ₂ N), 57.6 (NCH ₂ CH ₂ ), 54.3 (NCH ₂ CH ₃ ), 45.0 (q C), 31.8 (CH ₂ CH ₂ CH ₃ ), 29.6, 29.6, 29.5, 29.3 (tetradecyl CH ₂ ), 26.2 (CH ₂ CH ₂ CH ₂ O), 22.6 (CH ₂ CH ₃ ), 14.0 (Me), 8.3 (CH ₂ CH ₃ ). HR ESI MS m/z calc for C ₄₉ H ₁₀₄ BrN ₂ O ₄ (M+Br): 863.7179. Found: 863.7178. Example 5I

5 ₎ 5-Bis(dodecyloxymethyl)-Λ/,Λ/'-diethyl-yV,/V,Λ/',/V -tetramethyl-3,7-dioxa-1,9- nonanediammonium dibromide (5i)

CH ₃

5ι

[00139] Ethyl bromide (2.3 mL, 31 mmol, 10 eq), then sodium bicarbonate (1.30 g, 15.5 mmol, 5.0 eq) are added to a stirred solution of compound 3c (Example 3C) (2.13 g, 3.10 mmol) in THF (30 mL) and the resulting mixture is refluxed for 12 h, cooled to rt, filtered, and the filtrate is concentrated to give the title compound as a colorless solid. Crystallization from ethyl acetate and acetone gives colorless granules: yield 2.37 g, 91.1 %; mp 185 ⁰ C; R _F on basic alumina 0.45 (butanol, water, methanol 20: 5: 2); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.27-1.31 (br s, 36H, 18 x CH ₂ ), 1.45 (t, J = 7.2 Hz, 6H, 2 x NCH ₂ CH ₃ ) 1.51 (pentet, 4H, J = 6.2 Hz, 2 OCH ₂ CH ₂ ), 3.28 (s, 4H, dodecyl OCH ₂ C ), 3.32 (t, J = 6.6 Hz, 4H, dodecyl OCH ₂ ), 3.43 (s, 12H, 2 x N(CH ₃ J ₂ ), 3.47 (s, 4H, CCH ₂ O(CH ₂ ) ₂ N), 3.81 (q, 4H, J = 7.3 Hz, 2 x N(CH ₂ CH ₃ ) ₂ ), 3.92 (AA ^' part of AAΕB' pattern, 4H, 2 OCH ₂ CH ₂ N), 3.97 (BB ^" part of AA ^' BB ^' pattern, 4H, 2 NCH ₂ CH ₂ O); ¹³ C NMR δ 71.8 (CH ₂ CH ₂ OC), 70.9 (CCH ₂ O(CH ₂ ) ₂ N), 69.4 (CCH ₂ Ododecyl), 65.3 (OCH ₂ CH ₂ N), 63.1 (NCH ₂ CH ₂ O), 61.0 (NCH ₂ CH ₃ ) 51.3 (NCH ₃ ) ₂ , 45.1 (q C), 31.9 (CH ₂ CH ₂ CH ₃ ), 29.7, 29.7, 29.5, 29.4 (dodecyl CH ₂ ), 26.3 (CH ₂ CH ₂ CH ₂ O), 22.7 (CH ₂ CH ₃ ), 14.2 (Me), 8.9 (NCH ₂ CH ₃ ); HR ESI MS m/z calcd for C ₄ iH ₈₈ BrN ₂ O ₄ (M-Br) 5 751.5927, found 751.5922 .

Example 5J

5,5-Bis(dodecyloxymethyl)-Λ/,yV,Λ/',Λ/ -tetramethyl-3,7-dioxa-yV,yV'-dipropyl-1,9- nonanediammonium dibromide (5j)

5i

10 [00140] 1-Bromopropane (5.4 mL, 59 mmol, 10 eq), then sodium bicarbonate (2.47 g, 29.4 mmol, 5.0 eq) are added to a stirred solution of compound 3c (Example 3C) (4.05 g, 5.89 mmol) in THF (50 mL) and the resulting mixture is refluxed for 26 h, cooled to rt, filtered, and the filtrate is concentrated to give the title compound as a colorless solid. Crystallization from ethyl acetate and acetone gives colorless crystals: yield 4.83 g,

15 95.5%; mp 62°C; R _F on basic alumina 0.50 (butanol, water, methanol 20: 5: 2); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.7 Hz, 2 x Me), 1.05 (t, J = 7.3 Hz, 6H, 2 x N (CH ₂ ) ₂ CH ₃ ) 1.26- 1.31 (br s, 36H, 18 x CH ₂ ), 1.51 (pentet, 4H, J = 6.2 Hz, 2 OCH ₂ CH ₂ ), 1.86 (AA ¹ part of AA XX ^' pattern, 4H, 2 x NCH ₂ CH ₂ CH ₃ ), 3.28 (s, 4H, dodecylOCH ₂ C ), 3.32 (t, J = 6.6 Hz, 4H, dodecyl OCH ₂ ), 3.44 (s, 12H, 2xN(CH ₃ ) ₂ ), 3.48 (s, 4H, CCH ₂ O(CH ₂ ) ₂ N), 3.63 (XX

20 ^' part of AA ^' XX" pattern 4H, 2 x NCH ₂ CH ₂ CH ₃ ), 3.93 (AA ^" part of AA BB ^' pattern, 4H, 2, OCH ₂ CH ₂ N ₁ ) 3.99 (BB ^" part of AA ^' BB ^' pattern, 4H, 2,NCH ₂ CH ₂ O); ¹³ C NMR δ 71.8 (CH ₂ CH ₂ OC), 70.9 (CCH ₂ O(CHz) ₂ N), 69.5 (CCH ₂ Ododecyl), 67.1 (NCH ₂ CH ₂ CH ₃ ), 65.4 (OCH ₂ CH ₂ N), 63.6 (NCH ₂ CH ₂ O), 51.9 (NCH ₃ ) _2, 45.2 (q C), 31.9 (CH ₂ CH ₂ CH ₃ ), 29.7, 29.7, 29.5, 29.4 (dodecyl CH ₂ ), 26.2 (CH ₂ CH ₂ CH ₂ O), 22.7 (CH ₂ CH ₃ ), 16.5

25 (NCH ₂ CH ₂ CH ₃ ), 14.2 (Me), 10.8 (N(CH ₂ ) ₂ CH ₃ ); HR ESI MS m/z calcd for C ₄₃ H ₉₂ BrN ₂ O ₄ (M-Br) 779.6234, found 779.6209. Example 5K

Λ/.Λ/'-Dibutyl-S.δ-bistdodecyloxymethyO-^Λ/./V^/V'-te tramethyl-SJ-dioxa-I.S- nonanediammonium dibromide (5k)

5k

5 [00141] 1-Bromobutane (4.70 mL, 44.0 mmol, 10 eq ), then sodium bicarbonate (1.84 g, 22.0 mmol, 5.0 eq), are added to a stirred solution of compound 3c (Example 3C) (3.03 g, 4.4 mmol) in THF (40 mL) and the resulting mixture is refluxed for 33 h, cooled to rt, filtered, and the filtrate is concentrated to give the title compound as a colorless solid. Crystallization from ethyl acetate and methanol gives colorless crystals: yield 3.46 g,

10 88.7 %; mp 110 ⁰ C; R _F on basic alumina 0.53 (butanol, water, methanol 20: 5: 2); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.01 (t, J = 7.3 Hz, 6H, 2 x N (CH ₂ ) ₃ CH ₃ ) 1.26-1.31 (br s, 36H, 18 x CH ₂ ), 1.48 (sextet, 4H, J = 7.4 Hz, 2 x NCH ₂ CH ₂ CH ₂ CH ₃ ), 1.51 (pentet, 4H, J = 6.2 Hz, 2 OCH ₂ CH ₂ ), 1.78 (AA ^" part of AA XX ^' pattern, 4H, 2 x NCH ₂ CH ₂ CH ₂ CH ₃ ), 3.28 (s, 4H, dodecylOCH ₂ C), 3.32 (t, J = 6.6 Hz ₁ 4H, dodecyl OCH ₂ ),

15 3.35 (s, 4H, N(CH ₂ ) ₂ OCH ₂ C), 3.44 (s, 12H, 2xN(CH ₃ ) ₂ ) 3.48 (s, 4H, CCH ₂ O(CH ₂ ) ₂ N), 3.65 (XX ^' part of AA ^' XX ^' pattern, 4H, 2 x NCH ₂ CH ₂ CH ₂ CH ₃ ), 3.94 (AA ^' part of AA ^' BB ^' pattern, 4H, 2 OCH ₂ CH ₂ N), 3.99 (BB ^' part of AA ^' BB ^' pattern, 4H, 2 NCH ₂ CH ₂ O); ¹³ C NMR δ 71.9 (CH ₂ CH ₂ OC), 71.0 (CCH ₂ O(CH ₂ ) ₂ N), 69.5 (CCH ₂ Ododecyl), 65.6 (NCH ₂ CH ₂ CH ₂ CH ₃ ), 65.4 (OCH ₂ CH ₂ N), 63.7 (NCH ₂ CH ₂ O), 51.8 (NCH ₃ ) _2, 45.2 (q C), 32.0

20 (CH ₂ CH ₂ CH ₃ ), 29.8, 29.7, 29.6, 29.4 (dodecyl CH ₂ ), 26.3 (CH ₂ CH ₂ CH ₂ O), 24.9

(NCH ₂ CH ₂ CH ₂ CH ₃ ), 22.7 (CH ₂ CH ₃ ), 14.2 (Me), 13.9 (N (CH ₂ ) ₃ CH ₃ ); HR ESI MS m/z calcd for C ₄₅ H ₉₆ BrN ₂ O ₄ (M-Br) 807.6553, found 807.6548. Example 5L

Λ/,W,Λ/,Λ/',Λ/',Λr-Hexamethyl-6 ₎ 6-bis(octyloxymethyl)-4,8-dioxa-1,11- undecanediammonium diiodide (5I)

5I

5 [00142] Methyl iodide (1.6 g, 11 mmol) is added to a stirred solution of amine 3e

(Example 3E) (0.6 g, 1.1 mmol) in THF ( 50 mL) and the reaction mixture is stirred for 36 h, then allowed to cool to rt. The reaction mixture is concentrated and the residue is purified by flash chromatography using as eluant a gradient of 10 to 15% methanol in dichloromethane to give the title salt as an off-white solid: yield 0.7 g (68%); mp 212-

10 215°C; R _F 0.4 on basic alumina (8% methanol in dichloromethane); ¹ H NMR (DMSO-d ₆ ) δ 0.88 (t, 6H, J = 6.5 Hz, CH ₃ ), 1.25-1.37 (m, 20 H, 10 x CH ₂ ), 1.49 (p, 4H, J = 6.5 Hz, OCH ₂ CH ₂ ), 1.96 (4H, AA' part of AA ¹ BB ¹ pattern, NCH ₂ CH ₂ ), 3.11 (s, 18H, N(CH ₃ ) ₃ ), 3.31 (s, 4H, octylOCH ₂ C), 3.33 (t, 4H, J = 6.5 Hz, OCH ₂ ), 3.36 (s, 4H, CH ₂ OCH ₂ C), 3.38 (4H, BB' part of AA ¹ BB' pattern, NCH ₂ ), 3.42 (t, 4H, J = 6.0 Hz, OCH ₂ ); ¹³ C NMR (CDCI ₃ ) δ

15 70.7 (octyl CH ₂ O), 69.4 (OCH ₂ CH ₂ CH ₂ N), 68.8 (OCH ₂ C), 67.7 (OCH ₂ C), 63.3 (NCH ₂ ), 52.3 (N(CHa) ₃ ), 45.0 (qC), 31.1 (OCH ₂ CH ₂ ), 28.74, 28.65, 25.63 (decyl CH ₂ ), 23.0 (NCH ₂ CH ₂ ), 22.0 (CH ₃ CH ₂ ), 13.9 (CH ₃ ); HR ESI MS m/z calcd for C ₃₃ H ₇₂ IN ₂ O ₄ (M-I) 687.4531 , found 687.4522.

Example 5 M

20 6,6-Bis(decyloxymethyl)-/V,/V,/V,A/ ^l ,/V,/V-hexamethyl-4,8-dioxa-1,11- undecanediammmonium diiodide (5m)

5m

[00143] Methyl iodide (1.3 g, 9.5 mmol) is added to a stirred solution of amine 3f (Example 3F) (0.7 g, 1.2 mmol) in THF (70 mL) and the reaction mixture is stirred for 36 h, then allowed to cool to rt. The reaction mixture is concentrated and the residue is purified by flash chromatography using as eluant a gradient of 10 to 15% methanol in dichloromethane to give compound 5m as an off-white solid: yield 0.7 g (68%); mp 219- 222 ⁰ C; R _F 0.5 on basic alumina (7% methanol in dichloromethane); ¹ H NMR (CDCI ₃ ) δ 5 0.88 (t, 6H, J = 6.5 Hz, CH ₃ ), 1.22-1.35 (m, 28 H, 14 x CH ₂ ), 1.50 (p, 4H, J = 6.5 Hz, OCH ₂ CH ₂ ), 2.10 (m, 4H, NCH ₂ CH ₂ ), 3.31 (s, 4H, decylOCH ₂ C), 3.36 (t, 4H, J = 6.5 Hz, OCH ₂ ), 3.41 (s, 4H, CH ₂ OCH ₂ C), 3.48 (s, 18H, N(CH ₃ J ₃ ), 3.60 (t, 4H, J = 6.0 Hz, OCH ₂ ), 3.85 (m, 4H, NCH ₂ ); ¹³ C NMR (CDCI ₃ ) δ 71.8 (decyl CH ₂ O), 70.3 (OCH ₂ CH ₂ CH ₂ N), 69.3 (OCH ₂ C), 67.8 (OCH ₂ C), 65.2 (NCH ₂ ), 54.2 (N(CH ₃ ) ₃ ), 45.6 ( q,C), 32.0 (OCH ₂ CH ₂ ), 10 29.87, 29.81 , 29.72, 28.51 , 26.4 (decyl CH ₂ ), 24.3 (NCH ₂ CH ₂ ), 22.8 (CH ₂ CH ₃ ), 14.2 (CH ₃ ); HR ESI MS m/z calcd for C ₃₇ H ₈₀ IN ₂ O ₄ (M-I) 743.5157, found 743.5130.

Example 5N e.e-BistdodecyloxymethyO-Λ/.Λ/.W.Λr./V./V-hexamethyM.δ-d ioxa-i.ii- undecanediammmonium diiodide (5n)

₁ CH ₃

15 ^5π

[00144] Methyl iodide (1.5 g, 11 mmol) is added to a stirred solution of amine 3g (Example 3G) (0.70 g, 1.1 mmol) in THF (70 mL) and the reaction mixture is stirred for 36 h, then allowed to cool to rt. The reaction mixture is concentrated and the residue is purified by flash chromatography using as eluant a gradient of 10 to 15% methanol in

20 dichloromethane to give compound 5n as an off-white solid: yield 0.82 g (82%); mp 230- 234°C; R _F 0.58 on basic alumina (7% methanol in dichloromethane); ¹ H NMR (CDCI ₃ ) δ 0.88 (t, 6H, J = 6.5 Hz, CH ₃ ), 1.24-1.35 (m, 36 H, 18 x CH ₂ ), 1.51 (p, 4H, J = 6.5 Hz, OCH ₂ CH ₂ ), 2.10 (m, 4H, NCH ₂ CH ₂ ), 3.31 (s, 4H, decylOCH ₂ C), 3.35 (t, 4H, J = 6.5 Hz, OCH ₂ ), 3.40 (s, 4H, CH ₂ OCH ₂ C), 3.48 (s, 18H, N(CH ₃ ) ₃ ), 3.60 (t, 4H, J = 6.0Hz, OCH ₂ ),

25 3.82 (m, 4H, NCH ₂ ); ¹³ C NMR (CDCI ₃ ) δ 71.8 (dodecyl CH ₂ O), 70.4 (OCH ₂ CH ₂ CH ₂ N), 69.4 (OCH ₂ C), 67.9 (OCH ₂ C), 65.3 (NCH ₂ ), 54.3 (N(CH ₃ J ₃ ), 45.7 (qC), 32.1 (OCH ₂ CH ₂ ), 29.89, 29.74, 29.54, 26.4 (decyl CH ₂ ), 24.4 (NCH ₂ CH ₂ ), 22.9 (CH ₃ CH ₂ ), 14.3 (CH ₃ ); HR ESI MS m/z calcd for C ₄₁ H ₈₈ IN ₂ O ₄ (M-I) 799.5783, found 799.5815. Example 50

W,/V,Λ/,Λr,Λr,Λr-Hexamethyl-4,8-dioxa-6,6-bis(tetrade cyloxymethyl)-1 ,11 - undecanediammmonium diiodide (5o)

5o

5 [00145] Methyl iodide (3.1 g, 22 mmol) is added to a stirred solution of amine 3h

(Example 3H) (1.50 g, 2.23 mmol) in THF (100 mL) and the reaction mixture is stirred for 36 h then allowed to cool to rt. The reaction mixture is concentrated and the solid residue is crystallized from dichloromethane to give pure compound 5o as a shiny white solid: yield 1.5 g (70%); mp 222-225°C; R _F 0.6 on basic alumina (7% methanol in

10 dichloromethane); ¹ H NMR (CDCI ₃ ) δ 0.88 (t, 6H, J = 6.5 Hz, CH ₃ ), 1.22-1.37 (m, 44 H, 22x CH ₂ ), 1.51 (p, 4H, J = 6.5 Hz, OCH ₂ CH ₂ ), 2.09 (m, 4H, NCH ₂ CH ₂ ), 3.31 (s, 4H, decylOCH ₂ C), 3.35 (t, 4H, J = 6.5 Hz, OCH ₂ ), 3.41 (s, 4H, CH ₂ OCH ₂ C), 3.48 (s, 18H, N(CH ₃ J ₃ ), 3.61 (t, 4H, J = 6.0 Hz, OCH ₂ ), 3.90 (m, 4H, NCH ₂ ); ¹³ C NMR (CDCI ₃ ) δ 71.8 (tetradecyl CH ₂ O), 70.4 (OCH ₂ CH ₂ CH ₂ N), 69.4 (OCH ₂ C), 67.8 (OCH ₂ C), 65.2 (NCH ₂ ),

15 54.2 (N(CHa) ₃ ), 45.7 (qC), 32.1 (OCH ₂ CH ₂ ), 29.87, 29.72, 29.51 , 26.4 (tetradecyl CH ₂ ), 24.4 (NCH ₂ CH ₂ ), 22.8 (CH ₃ CH ₂ ), 14.3 (CH ₃ ); HR ESI MS m/z calcd for C ₄₅ H ₉₆ IN ₂ O ₄ (M-I) 855.6409, found 855.6432.

Example 6A

Diethyl 3,13-diazonia-3,3,13,13-tetramethyl-8,8-bis(octyloxymethyl)- 6,10-dioxa- 20 pentadecanedioate dibromide (6a)

6a

[00146] A solution of compound 3a (Example 3A) (0.61g, 1.21 mmol) and ethyl bromoacetate (0.31 mL, 2.79 mmol, 2.3 eq) in diethyl ether (20 ml.) is stirred for 26 h, to give a colorless solid that is isolated by filtration, then washed with ether. The solid is crystallized from ethyl acetate and methanol to give the title compound as a colorless crystalline solid: yield 0.88 g, 84 %; mp 110-111 ⁰ C; R _F on basic alumina 0.59 (butanol: water: methanol 20: 5 : 2); ¹ H NMR δ 0.88 (t, 6H, J = 6.9 Hz, 2 x Me), 1.27 (brs, 2OH, 10 x CH ₂ ), 1.32 (t, 6H, J = 7.2 Hz, 2 x Me), 1.50 (pentet, 4H, J = 6.0 Hz, 2 OCH ₂ CH ₂ ), 3.28 (s, 4H, octyl OCH ₂ C), 3.33 (t, 4H, J = 6.6 Hz, octyl OCH ₂ C) ₁ 3.50 (s, 4H, CCH ₂ O(CH ₂ ) ₂ N), 3.71 (s, 12H, 2N(CH ₃ ) ₂ ), 3.96 (br AA ^" part of AA ¹ BB ^" pattern, 4H, 2 OCH ₂ CH ₂ N), 4.27 (q, 4H, J = 7.2 Hz, OCH ₂ CH ₃ ), 4.32 (br BB ^' part of AA" BB ^' pattern, 4H, 2 NCH ₂ CH ₂ O), 4.96 (s, 4H, CH ₂ COOR); ¹³ C NMR δ 164.9 (CH ₂ COOR), 71.8 (CH ₂ CH ₂ OC), 71.1 (CCH ₂ O(CH ₂ ) ₂ N), 69.4 (CCH ₂ O octyl), 65.4 (OCH ₂ CH ₂ N), 64.1 (NCH ₂ CH ₂ O), 62.7 (CH ₂ COOCH ₂ CH ₃ ), 62.3 (CH ₂ COOCH ₂ CH ₃ ), 52.4 (N (CH ₃ J ₂ ), 45.1 (qC), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.6, 29.5, 29.3, (octyl CH ₂ ), 26.2 (CH ₂ CH ₂ CH ₂ O), 22.7 (CH ₂ CH ₃ ), 14.12 (Me), 14.06 (CH ₃ CH ₂ ); HR ESI MS m/z calc for C ₃₇ H ₇₆ N ₂ O ₈ ^ ((M- 2Br)/2) 338.2795, found 338.2811.

Example 6B

Diethyl 3,13-diazonia-8,8-bis(decyloxymethyl)-3,3,13,13-tetramethyl- 6,10- dioxapentadecanedioate dibromide (6b)

EtOOC

6b

[00147] A solution of compound 3b (Example 3B) (1.86 g, 3.33 mmol) and ethyl bromoacetate (0.85 mL,7.66 mmol, 2.3 eq) in diethyl ether (35 mL) is stirred for 26 h then filtered and concentrated to give a colorless solid that is crystallized from ethyl acetate and methanol to give the title compound as a colorless crystalline solid, yield: 2.66 g, 90 %; mp 114-115°C; R _F on basic alumina 0.61 (butanol: water: methanol 20: 5 : 2); ¹ H NMR δ 0.88 (t, 6H, J = 6.9 Hz, 2 x Me), 1.27 (brs, 28H, 14 x CH ₂ ), 1.32 (t, 6H, J = 7.2 Hz, 2 x Me), 1.50 (pentet, 4H, J = 6.0 Hz, 2 OCH ₂ CH ₂ ), 3.27 (s, 4H, decyl, OCH ₂ C), 3.32 (t, 4H, J = 6.5 Hz, decyl OCH ₂ C), 3.49 (s, 4H, CCH ₂ O(CH ₂ ) ₂ N), 3.71 (s, 12H, 2N(CH ₃ ) ₂ ), 3.94 (br AA ^' part of AA ^' BB ^" pattern, 4H, 2 OCH ₂ CH ₂ N), 4.27 (q, 4H, J = 7.2 Hz, OCH ₂ CH ₃ ), 4.31 (br BB ^' part of AA ^' BB ^' pattern, 4H, 2 NCH ₂ CH ₂ O ), 4.96 (s, 4H, CH ₂ COOR); ¹³ C NMR δ 165.0 (CH ₂ COOR), 71.9 (CH ₂ CH ₂ OC), 71.1 (CCH ₂ O(CH ₂ ) ₂ N), 69.4 (CCH ₂ O decyl), 65.4 (OCH ₂ CH ₂ N), 64.3 (NCH ₂ CH ₂ O), 62.8 (CH ₂ COOCH ₂ CH ₃ ), 62.4 (CH ₂ COOCH ₂ CH ₃ ), 52.5 (N (CH ₃ ).), 45.2 (qC), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.8, 29.7, 29.6, 29.5 (decylCH ₂ ), 26.4 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.2 (Me), 14.1 (CH ₃ CH ₂ ); HR ESI MS m/z calc for C ₄₁ H ₈₄ N ₂ O ₈ /2 ((M-2Br)/2) 366.3108, found 366.3112.

Example 6C

Diethyl 3,13-diazonia-8,8-bis(dodecyloxymethyl)-3,3,13,13-tetramethy l-6,10- dioxapentadecanedioate dibromide (6c)

EtOOC COOEt

6c

[00148] A solution of compound 3c (Example 3C) (1.77 g, 2.88 mmol) and ethyl bromoacetate (0.73 ml_, 6.60 mmol, 2.3 eq) in diethyl ether (35 mL) is treated following the procedure of Example 6A to give the title compound as a colorless solid that is crystallized from ethyl acetate and methanol to give a colorless crystalline solid, yield: 2.05 g, 73%; mp 119-120 ⁰ C; R _F on basic alumina 0.63 (butanol: water: methanol 20: 5 : 2); ¹ H NMR δ 0.88 (t, 6H, J = 6.9 Hz, 2 x Me), 1.26 (brs, 36H, 18 x CH ₂ ), 1.32 (t, 6H, J = 7.2 Hz, 2 x Me), 1.51 (pentet, 4H, J = 6.4 Hz, 2 OCH ₂ CH ₂ ), 3.27 (s, 4H, dodecyl, OCH ₂ C), 3.33 (t, 4H, J = 6.6 Hz, dodecyl, OCH ₂ C), 3.49 (s, 4H, CCH ₂ O(CH ₂ ) ₂ N), 3.70 (s, 12H, 2N(CH ₃ ) ₂ ), 3.95 (br AA ^' part of AA ^' BB ^" pattern, 4H, 2 OCH ₂ CH ₂ N), 4.26 (q, 4H, J = 7.2 Hz, OCH ₂ CH ₃ ), 4.31 (br BB ^' part of AA ^' BB ^' pattern, 4H, 2 NCH ₂ CH ₂ O ), 4.94 (s, 4H, CH ₂ COOR); ¹³ C NMR δ 164.9 (CH ₂ COOR), 71.8 (CH ₂ CH ₂ OC), 71.1 (CCH ₂ O(CH ₂ ) ₂ N), 69.4 (CCH ₂ O dodecyl), 65.4 (OCH ₂ CH ₂ N), 64.1 (NCH ₂ CH ₂ O), 62.7 (CH ₂ COOCH ₂ CH ₃ ), 62.3 (CH ₂ COOCH ₂ CH ₃ ), 52.4 (N(CH ₃ ) ₂ ), 45.1 (qC), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.7, 29.5, 29.4 (dodecylCH ₂ ), 26.3 (CH ₂ CH ₂ CH ₂ O), 22.7 (CH ₂ CH ₃ ), 14.12 (Me), 14.06 (CH ₃ CH ₂ ); HR ESI MS m/z calcd for C ₄₅ H ₉₂ N ₂ O ₈ /2 ((M-2Br)/2) 394.3421 , found 394.3424. Example 6D

Diethyl 3,13-diazonia-3,3,13,13-tetramethyl-6,10-dioxa-8,8- bis(tetradecyloxymethyl)pentadecanedioate dibromide (6d)

6d

[00149] A solution of compound 3d (Example 3D) (0.78 g, 1.22 mmol) and ethyl bromoacetate (0.31 mL, 2.80 mmol, 2.3 eq) in diethyl ether (25 mL) is treated following the procedure of Example 6A to give the title compound (6d) as a colorless solid that precipitated from ethyl acetate and methanol to give a colorless amorphous solid, yield: 0.89 g, 71 %; mp 116-117°C; R _F on basic alumina 0.66 (butanol: water: methanol 20: 5 : 2); ¹ H NMR δ 0.88 (t, 6H, J = 6.9 Hz, 2 x Me), 1.26 (brs, 44H, 22 x CH ₂ ), 1.32 (t, 6H, J = 7.2 Hz, 2 x Me), 1.50 (pentet, 4H, J = 6.0 Hz, 2 OCH ₂ CH ₂ ), 3.27 (s, 4H, tetradecyl, OCH ₂ C), 3.32 (t, 4H, J = 6.6 Hz, tetradecyl, OCH ₂ C), 3.48 (s, 4H, CCH ₂ O(CH ₂ ) ₂ N), 3.71 (s, 12H, 2N(CH ₃ ) ₂ ), 3.93 (br AA ^' part of AA ^' BB ^" pattern, 4H, 2 OCH ₂ CH ₂ N), 4.26 (q, 4H, J = 7.2 Hz, COCH ₂ CH ₃ ), 4.30 (br BB ^' part of AA ^' BB ^' pattern, 4H, 2 NCH ₂ CH ₂ O ), 4.95 (s, 4H, CH ₂ COOR); ¹³ C NMR δ 164.9 (CH ₂ COOR), 71.8 (CH ₂ CH ₂ OC), 71.1

(CCH ₂ O(CHz) ₂ N), 69.4 (CCH ₂ O tetradecyl), 65.4 (OCH ₂ CH ₂ N), 64.2 (NCH ₂ CH ₂ O), 62.7 (CH ₂ COOCH ₂ CH ₃ ), 62.4 (CH ₂ COOCH ₂ CH ₃ ), 52.5 (N (CH ₃ ) ₂ ), 45.1 (qC), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.8, 29.7, 29.6, 29.4 (tetradecyl CH ₂ ), 26.3 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.2 (Me), 14.1 (CH ₃ CH ₂ O ); HR ESI MS m/z calcd for C ₄₉ H ₁₀₀ N ₂ O ₈ ^ ((M-2Br)/2) 422.3734, found 422.3721.

Example 7A

3,13-Diazonia-3,3,13,13-tetramethyl-8,8-bis(octyloxymethy l)-6,10- dioxapentadecanedioate (7a)

7a

5 [00150] Compound 6a (Example 6A) (0.44 g, 0.51 mmol) and IRA-400 anion-exchange resin (OH ^" ) (11.0 g) in ethanol (30 ml_) are stirred at rt for 24 h. The reaction mixture is filtered and the filtrate is concentrated to a semi-solid residue that precipitated from ethyl acetate and methanol to give the title compound as a colorless waxy mass, yield: 0.28 g, 90 %; mp 183°C; R _F on basic alumina 0.37 (butanol: water: methanol 20: 5 : 2); ¹ H NMR

10 δ 0.88 (t, 6H, J = 6.7 Hz, 2 x Me), 1.28-1.32 (brs, 2OH, 10 x CH ₂ ), 1.51 (pentet, 4H, J = 6.2 Hz, 2 OCH ₂ CH ₂ ), 3.29 (s, 4H, octyl OCH ₂ C), 3.33 (t, 4H, J = 6.4 Hz, octyl OCH ₂ ), 3.39 (s, 4H, CCH ₂ O(CH ₂ ) ₂ N), 3.39 (s, 12H, 2N(CH ₃ ) ₂ ), 3.82 (br AA ^' part of AA ^' BB ^' pattern, 4H, 2 NCH ₂ CH ₂ O), 3.99 (BB ^" part of AAΕB ^' pattern, 4H, 2 OCH ₂ CH ₂ N), 3.99 (s, 4H, CH ₂ COO ); ¹³ C NMR δ 166.2 (CH ₂ COO ), 71.4 (CH ₂ CH ₂ OC), 70.6 (CCH ₂ O(CH ₂ ) ₂ N),

15 69.2 (CCH ₂ O octyl), 65.46 (NCH ₂ CH ₂ O), 65.3 (OCH ₂ CH ₂ N), 62.4 (CH ₂ COO ), 52.0 (N (CH ₃ ) ₂ ), 44.7 (q C), 31.6 (CH ₂ CH ₂ C H ₃ ), 29.3, 29.2, 29.1 (octyl CH ₂ ), 25.9 (CH ₂ CH ₂ CH ₂ O), 22.4 (CH ₂ CH ₃ ), 13.8 (Me); HR ESI MS m/z calcd for C ₃₃ H ₆₇ N ₂ O ₈ (M+H) 619.4892, found 619.4859.

Example 7B

20 3,13-Diazonia-8,8-bis(decyloxymethyl)-3,3,13,13-tetramethyl- 6,10- dioxapentadecanedioate (7b)

7b [00151] Compound 6b (Example 6B) (2.21 g, 2.55 mmol) and IRA-400 anion-exchange resin (OH ^" ) (11.6 g) in ethanol (40 mL) are stirred at rt following the procedure of Example 7A The reaction mixture is filtered and concentrated to a semi-solid residue that precipitated from ethyl acetate and methanol to give the title compound as a colorless waxy solid, yield: 1.47 g, 89 %; mp 175°C; R _F on basic alumina 0.35 (butanol: water: methanol 20: 5 : 2); ¹ H NMR δ 0.88 (t, 6H, J = 6.9 Hz, 2 x Me), 1.21-1.32 (brs, 28H, 14 x CH ₂ ,), 1.51 (pentet, 4H ₁ J = 6.5 Hz, 2 OCH ₂ CH ₂ ), 3.28 (s, 4H, decylOCH ₂ C), 3.33 (t, 4H, J = 6.4 Hz, decyl OCH ₂ ), 3.38 (s, 12H, 2N(CH ₃ ) ₂ ), 3.39 (s, 4H, CCH ₂ O(CH ₂ ) ₂ N), 3.81 (br AA ^" part of AA ^' BB ^' pattern, 4H, 2 NCH ₂ CH ₂ O), 3.95 (BB ^' part of AA ^' BB ^" pattern, 4H, 2 OCH ₂ CH ₂ N) ₁ 4.12 (s, 4H, CH ₂ COO ); ¹³ C NMR δ 167.9 (CH ₂ COO ^" ), 71.7 (CH ₂ CH ₂ OC), 70.8 (CCH ₂ O(CH ₂ ) ₂ N), 69.3 (CCH ₂ Odecyl), 65.6 (NCH ₂ CH ₂ O), 65.5 (OCH ₂ CH ₂ N), 63.1 (CH ₂ COO ) ₁ 52.1 (N (CH ₃ J ₂ ), 45.1 (q C), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.7, 29.7, 29.6, 29.4 (decyl CH ₂ ), 26.3 (CH ₂ CH ₂ CH ₂ O) ₁ 22.7 (CH ₂ CH ₃ ), 14.1 (Me); HR ESI MS m/z calcd for C ₃₇ H ₇₄ N ₂ O ₈ Na (M+Na) 697.5337, found 697.5304. Example 7C

3,13-Diazonia-8,8-bis(dodecyloxymethyl)-3,3,13,13-tetrame thy 1-6,1 O- dioxapentadecanedioate (7c)

7c

[00152] Compound 6c (Example 6C) (1.54 g, 1.62 mmol) and IRA-400 anion-exchange resin (OH ^" ) (12.0 g) in ethanol (50 mL) are stirred at rt ollowing the procedure of Example 7A. The reaction mixture is filtered and concentrated to a semi-solid residue that is crystallized from ethyl acetate and methanol to give the title compound (7c) as colorless granules: yield 1.1 g, 93 %; mp 170-171 ⁰ C; R _F on basic alumina 0.33 (butanol: water: methanol 20: 5 : 2); ¹ H NMR δ 0.88 (t, 6H, J = 6.9 Hz, 2 x Me), 1.26 (brs, 36H, 18 x CH ₂ ), 1.51 (pentet, 4H, J = 6.5 Hz, 2 OCH ₂ CH ₂ ), 3.28 (s, 4H, dodecyl OCH ₂ C), 3.33 (t, 4H ₁ J = 6.4 Hz ₁ dodecyl OCH ₂ ), 3.39 (s, 12H, 2N(CH ₃ ) ₂ ) 3.4 (s, 4H, CCH ₂ O(CH ₂ ) ₂ N), 3.83 (br AA ^' part of AA ^' BB ^' pattern, 4H, 2 NCH ₂ CH ₂ O), 3.99 (BB ^' part of AA ^' BB ^' pattern, 4H, 2 OCH ₂ CH ₂ N), 3.99 (s, 4H, CH ₂ COO ); ¹³ C NMR δ 166.3 (CH ₂ COO ), 71.8 (CH ₂ CH ₂ OC), 70.9 (CCH ₂ O(CH ₂ ) ₂ N), 69.5 (CCH ₂ O dodecyl), 65.7 (NCH ₂ CH ₂ O), 65.5 (OCH ₂ CH ₂ N), 62.7 (CH ₂ COO ^" ), 52.4 (N(CH ₃ J ₂ ), 45.1(q C), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.7, 29.6, 29.4 (dodecyl CH ₂ ), 26.3 (CH ₂ CH ₂ CH ₂ O), 22.7 (CH ₂ CH ₃ ), 14.1 (Me); HR ESI MS m/z calcd for C _4I H ₈₃ N ₂ O ₈ (M+H) 731.6144, found 731.6117. Example 7D

3,13-Diazonia-3,3,13,13-tetramethyl-6,10-dioxa-8,8- bis(tetradecyloxymethyl)pentadecanedioate (7d)

7d

[00153] Compound 6d (Example 6D) (0.89 g, 0.88 mmol) and IRA-400 anion-exchange resin (OH ^" ) (11.2 g) in ethanol (30 mL) are stirred at rt for 24 h. The reaction mixture is filtered and the filtrate is concentrated to a colorless semi-solid residue that is crystallized from ethyl acetate and methanol to give the title compound as a colorless powder: yield 0.65 g, 92 %; mp 168°C; R _F on basic alumina 0.30 (butanol: water: methanol 20: 5 : 2); ¹ H NMR δ 0.88 (t, 6H ₁ J = 6.9 Hz, 2 x Me), 1.26-1.31 (brs, 44H, 22 x CH ₂ ), 1.50 (pentet, 4H ₁ J = 6.2 Hz, 2 OCH ₂ CH ₂ ), 3.28 (s, 4H, tetradecylOCH ₂ C), 3.33 (t, 4H, J = 6.4 Hz, tetradecyl OCH ₂ ), 3.40 (s, 12H, 2N(CH ₃ ) ₂ ), 3.40 (s, 4H, CCH ₂ O(CH ₂ ) ₂ N), 3.83 (br AA' part of AA ^' BB ^' pattern, 4H, 2 NCH ₂ CH ₂ O), 3.98 (BB ^' part of AA ^' BB ^' pattern, 4H, 2 OCH ₂ CH ₂ N), 4.10 (s, 4H, CH ₂ COO ); ¹³ C NMR δ 166.1 (CH ₂ COO ), 71.8 (CH ₂ CH ₂ OC), 70.9 (CCH ₂ O(CH ₂ ) ₂ N), 69.5 (CCH ₂ Odecyl), 65.7 (NCH ₂ CH ₂ O), 65.5 (OCH ₂ CH ₂ N), 62.9 (CH ₂ COO ), 52.4 (N (CH ₃ J ₂ ), 45.2 (q C), 32.1 (CH ₂ CH ₂ CH ₃ ), 29.9, 29.8, 29.7, 29.5

(tetradecyl CH ₂ ), 26.4 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.2 (Me); HR ESI MS m/z calcd for C ₄₅ H ₉₀ N ₂ O ₈ Na (M+Na) 809.6589, found 809.6567. Example 8A

1 ,3-Diiodo-2,2-bis(octyloxymethyl)propane (8a)

H ₃ C(H ₂ C) ₇

8a

[00154] Iodine (10.2 g, 0.0415 mol, 2.5 eq), imidazole (2.73 g, 0.0415 mol, 2.5 eq) and triphenylphosphine (8.94 g, 0.0353 mol, 2.2 eq) are added to a solution of compound 2a (Example 2A) (5.80 g, 0.0161 mol) in anhydrous toluene (200 ml_) and the reaction mixture is refluxed for 3 h. More iodine is then added to consume excess triphenylphosphine and reflux is continued for 1 h. The cooled reaction mixture is stirred for 10 min each with saturated sodium bicarbonate (100 ml.) and 10% aqueous sodium thiosulfate (200 mL) solutions. The organic layer is washed with water (3 x 50 ml_), dried (MgSO ₄ ) and concentrated. The residue is taken up in hexanes and the solution is passed a short silica gel column. Concentration gives the title compound (8a) as a colorless oil: 7.89 g, 86%; R _F 0.34 (98:2 hexanes: dichloromethane); ¹ H NMR δ 0.89 (t, 6H, J = 6.3 Hz, 2 x Me), 1.22-1.36 (br s, 2OH, 10 x CH ₂ ), 1.55 (pentet, 4H, J = 6.1 Hz, 2 OCH ₂ CH ₂ ), 3.33 (s, 4H, CH ₂ I), 3.35 (s, 4H, OCH ₂ C), 3.42 (t, 4H, dodecyl OCH ₂ ); ¹³ C NMR δ 71.7 (CH ₂ CH ₂ OC), 70.9 (CCH ₂ OCH ₂ C), 41.7 (q C), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.69, 29.56, 29.47 (3 octyl CH ₂ ), 26.3 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.3 (Me), 12.1 (CH ₂ I); HR ESI MS; m/z calc for C ₂₁ H ₄₃ I ₂ O ₂ (M+H) 581.1353, found 581.1351.

Example 8B 1,3-Diiodo-2,2-bis(decyloxymethyl)propane (8b)

8b

[00155] A solution of compound 2b (Example 2B) (10.0 g, 24.3 mmol) in toluene (300 mL) is refluxed with iodine (16.3 g, 25.9 mmol, 2.7 eq), imidazole (4.08 g, 60.0 mmol, 2.5 eq) and triphenylphosphine (13.4 g, 50.4 mmol, 2.1 eq) following the procedure of Example 8A to give the title compound (8b) as an oil: 14.4 g, 94%; R _F 0.43 (98:2 hexanes: dichloromethane); ¹ H NMR δ 0.88 (t, 6H, J = 6.9 Hz, 2 x Me), 1.22-1.36 (br s,

28H, 14 x CH ₂ ), 1.54 (pentet, 4H, J = 6.8 Hz, 2 CH ₂ CH ₂ O), 3.32 (s, 4H, CH ₂ I), 3.35 (s, 4H, OCH ₂ C), 3.41 (t, 4H, J = 6.5 Hz, 2 decyl OCH ₂ ); ¹³ C NMR δ 71.7 (CH ₂ CH ₂ OC), 70.9 (CCH ₂ OCH ₂ C), 41.7 (q C), 32.1 (CH ₂ CH ₂ CH ₃ ), 29.65, 29.63, 29.48, 29.37 (6 dodecyl CH ₂ ), 29.58 (OCH ₂ CH ₂ ), 26.3 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.3 (Me), 12.1 (CH ₂ I); HR ESI MS; m/z calc for C ₂₅ H _5I I ₂ O ₂ 637.1979, found 637.1976. Example 8C

1 ,3-Diiodo-2,2-bis(dodecyloxymethyl)propane (8c)

₁ CH ₃

8c

[00156] Treatment of compound 2c (Example 2C) (10.0 g, 21.2 mmol) in toluene (300 ml.) with iodine (14.0 g, 52.8 mmol, 2.5 eq), imidazole (3.58 g, 52.8 mol, 2.5 eq) and triphenylphosphine (13.82 g, 52.8 mol, 2.5 eq) following the procedure of Example 8A gives the title compound (8c) as an oil: 14.0 g, 95%; R _F 0.44 (98:2 hexanes: dichloromethane); ¹ H NMR δ 0.88 (t, 6H, J = 6.5 Hz, 2 x Me), 1.22-1.36 (br s, 36H, 18 x CH ₂ ), 1.55 (pentet, 4H, J = 6.4 Hz, 2 OCH ₂ CH ₂ ), 3.32 (s, 4H, CH ₂ I), 3.35 (s, 4H, OCH ₂ C), 3.41 (t, 4H, dodecyl OCH ₂ ); ¹³ C NMR δ 71.7 (CH ₂ CH ₂ OC), 70.9 (CCH ₂ OCH ₂ C), 41.7 (q C), 32.1 (CH ₂ CH ₂ CH ₃ ), 29.92, 3 x 29.88, 29.79, 29.59 (6 dodecyl CH ₂ ), 29.68

(OCH ₂ CH ₂ ), 26.3 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.3 (Me), 12.1 (CH ₂ I); HR ESI MS; m/z calc for C ₂₉ H ₅₉ O ₄ 693.2605, found 693.2605.

Example 8D

1 ,3-Diiodo-2,2-bis(tetradecyloxymethyl)propane (8d)

8 ^d

[00157] Treatment of compound 2d (Example 2D) (5.0 g, 9.5 mmol) in toluene (200 mL) with iodine (7.20 g, 28.4 mmol, 3.0 eq), imidazole (1.60 g, 23.6 mmol, 2.5 eq) and triphenylphosphine (7.19 g, 28.4 mmol, 2.9 eq) following the procedure of Example 8A gives the title compound (8d) as a colourless solid: yield 6.36 g, 90 %; mp 27-28°C; R _F 0.45 (98:2 hexanes: dichloromethane); ¹ H NMR δ 0.88 (t, 6H, J = 7.0 Hz, 2 x Me), 1.22- 1.36 (br s, 44H, 22 x CH ₂ ), 1.53 (pentet, 4H, J = 6.9 Hz, 2 OCH ₂ CH ₂ ), 3.33 (s, 4H, CH ₂ I), 3 35 (s, 4H, OCH ₂ C), 3 41 (t, 4H, tetradecyl OCH ₂ ), ¹³ C NMR δ 71 8 (CH ₂ CH ₂ OC), 71 0 (CCH ₂ OCH ₂ C), 41 8 (q C), 32 1 (CH ₂ CH ₂ CH ₃ ), 29 87, 29 86, 29 85, 29 82, 2 x 29 81 , 29 72, 29 52 (8 tetradecyl CH ₂ ), 29 61 (OCH ₂ CH ₂ ), 26 4 (CH ₂ CH ₂ CH ₂ O), 22 9 (CH ₂ CH ₃ ), 14 3 (Me), 12 1 (CH ₂ I), LR ESI m/z calc for C ₃₃ H ₆₇ I ₂ O ₂ 749 32, found 749 1 Anal CaIc for C ₃₃ H ₆₆ I ₂ O ₂ C 52 94, H 8 89 Found C 53 14, H 9 20

Example 9A

Λ/,Λ/,/V,Λ/'-Tetramethyl-2,2-bis(octyloxymethyl)-1,3-p ropanediaminium dichloride (9a)

H ₃ C

9a [00158] Compound 8a (Example 8A) (9 98 g, 17 2 mmol), dimethylamine in THF (2 M, 87 mL, 0 17 mol, 10 eq) and potassium carbonate (5 9 g, 43 mmol, 2 5 eq) are added to a sealed tube with the aid of THF (10 mL) The reaction mixture is stirred at 160~170°C After one week, all of the starting material has been consumed and the reaction mixture is filtered and the solvent is removed in vacuo at 35~40°C to give a yellow oil, 1 ,3- bιs(dιmethylamιno)-2,2-bιs(octyloxymethyl)propane The crude oil is taken up in dichloromethane (50 mL) and the resulting solution is shaken with ice cold 2 M HCI (75 mL) The aqueous layer is extracted with dichloromethane (2 x 50 mL), then the combined organic layers are washed with water (20 mL), dried (MgSO ₄ ), and concentrated to give the title compound (9a) as a light yellow crystalline solid that is recrystallized from ethyl acetate, acetone 15 1 to give clear rectangular crystals yield 5 62 g, 67 3%, mp 145 ⁰ C, R _F 0 29 on basic alumina (hexanes, ethyl acetate, methanol 96 4 O 4), ¹ H NMR δ O 88 ppm (t, 6H, J = 6 9 Hz, 2 x Me), 1 26 -1 33 (br s, 2OH, 1O x CH ₂ ), 1 56 (pentet, 4H, J = 6 6 Hz, 2 OCH ₂ CH ₂ ), 2 97 (s, 12H, 2 x N(CH ₃ J ₂ ), 3 47 (t, 4H, J = 6 6 Hz, octyl OCH ₂ ), 3 68 (s, 4H, OCH ₂ C), 3 79 (s, 4H, CH ₂ N), 11 78 (brs, HN), ¹³ C NMR δ 71 7 (CH ₂ CH ₂ OC), 66 9 (CCH ₂ OCH ₂ C), 58 6 (CH ₂ N), 47 5 (N(CH ₃ J ₂ ), 44 5 (q C), 31 8 (CH ₂ CH ₂ CH ₃ ), 29 5, 29 3, 29 2, (3 octyl CH ₂ ), 26 2 (CH ₂ CH ₂ CH ₂ O), 22 6 (CH ₂ CH ₃ ), 14 1 (Me), HR ESI MS m/z calc for C ₂₅ H ₅₅ N ₂ O ₂ (M-H-2CI) 415 4264 Found 415 4260 Example 9B

2,2-Bis(decyloxymethyl)-Λ/,Λ/,Λ/' _l Λ/ ^l -tetramethyl-1,3-propanediaminium dichloride (9b)

H3C(

9b

5 [00159] Compound 8b (Example 8B) (6.88 g, 10.8 mmol), dimethylamine in THF (2M, 54 ml_, 0.11 mol, 10 eq), and potassium carbonate (3.72 g, 27.0 mmol, 2.5 eq) are added to a sealed tube with the aid of THF (10 ml_). The mixture is heated in sealed tube following the procedure of Example 9A to give a yellow oil, 1 ,3-bis(dimethylamino)-2,2- bis(decyloxymethyl)propane that is taken up in dichloromethane (30 ml_). This solution is

10 shaken with ice cold 2 M HCI (30 mL) following the procedure of Example 9A to give colourless crystals that are recrystallized from ethyl acetate/acetone 2/1 to give colorless needles: yield 3.95 g, 67.5 %; mp 130-133 ⁰ C; R _F 0.32 on basic alumina (hexanes, ethyl acetate, methanol 96: 4: 0.4); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.26 -1.32 (br s, 28H, 14 x CH ₂ ), 1.55 (pentet, 4H, J = 6.6 Hz, 2 OCH ₂ CH ₂ ), 2.97 (s, 12H, 2 x

15 N(CHs) ₂ ), 3.47 (t, 4H, J = 6.6 Hz, decyl OCH ₂ ), 3.67 (s, 4H, OCH ₂ C), 3.81 (s, 4H, CH ₂ N), 11.85 (brs, HN); ¹³ C NMR δ 71.8 (CH ₂ CH ₂ OC), 66.9 (CCH ₂ OCH ₂ C), 58.6 (CH ₂ N), 47.7 (N(CHa) ₂ ), 44.6 (q C), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.7, 29.7, 29.6, 29.5, 29.4, (decyl CH ₂ ), 26.3 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.2 (Me); HR ESI MS m/z calc for C ₂₉ H ₆₃ N ₂ O ₂ (M-H- 2Cl): 471.4890. Found: 471.4886.

20 Example 9C

2,2-Bis(dodecyloxymethyl)-/V,A/,/V,W-tetramethyl-1,3-prop anediaminium dichloride (9c)

H ₃ C( ₁ CH ₃

[00160] Compound 8c (Example 8C) (11.72 g, 16.9 mmol), dimethylamine in THF (2M, 25 85 mL, 0.17 mol, 10 eq), potassium carbonate (5.83 g, 42.2 mmol), and THF (10 mL) are heated and stirred at 160~170°C in a sealed tube following the procedure of Example 9A. The reaction mixture is filtered and the filtrate is concentrated at 35~40°C to give a yellow crystalline solid, 1 ,3-bis(dimethylamino)-2,2-bis(dodecyloxymethyl)propane. The crude solid is taken up in dichloromethane (50 ml_) and ice cold 2 M HCI (50 mL) is added to give an off white crystalline solid. The title compound is recrystallized from ethyl acetate acetone to give colourless rectangular crystals: yield 6.90 g, 68.2 %; mp 128- 130 ⁰ C; R _F 0.34 on basic alumina (hexanes, ethyl acetate, methanol 96: 4: 0.4); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.26 -1.31 (br s, 36H, 18 x CH ₂ ), 1.55 (pentet, 4H, J = 6.5 Hz, 2 OCH ₂ CH ₂ ), 2.97 (s, 12H, 2 x N(CH ₃ ) ₂ ), 3.47 (t, 4H, J = 6.6 Hz, dodecyl OCH ₂ ), 3.67 (s, 4H, OCH ₂ C), 3.78 (s, 4H, CH ₂ N), 11.69 (brs, HN); ¹³ C NMR δ 71.7 (CH ₂ CH ₂ OC), 66.9 (CCH ₂ OCH ₂ C), 58.6 (CH ₂ N), 47.6 (N(CH ₃ ) ₂ ), 44.5 (q C), 31.9 (CH ₂ CH ₂ CH ₃ ), 29.7, 29.6, 29.6, 29.6, 29.5,29.4, 29.3 (dodecyl CH ₂ ), 26.2 (CH ₂ CH ₂ CH ₂ O), 22.7 (CH ₂ CH ₃ ), 14.1 (Me); HR ESI MS: m/z calc for C ₃₃ H _7I N ₂ O ₂ (M-H- 2Cl): 527.5516, found 527.5517.

Example 9D W,W,ΛT, W-Tetramethyl-2,2-bis(tetradecyloxymethyl)-1 ,3-propanediaminium dichloride (9d)

H ₃ C( H ₃

9d

[00161] A mixture of compound 8d (Example 8D) (15.24 g, 20.37 mmol), dimethyl amine in THF (2M, 50.9 mL, 102 mmol, 5.0 eq), and potassium carbonate (7.03 g, 50.93 mmol) are heated in a sealed tube following the procedure of Example 9A, except that the same amount of dimethylamine was added after 48 h, to give an offwhite crystalline solid, 1 ,3-bis(dimethylamino)-2,2-bis(tetradecyloxymethyl)propane, that is taken up in dichloromethane (50 mL). The resulting solution is shaken with ice cold 2 M HCI (50 mL). The aqueous layer is extracted with dichloromethane (3 x 50 mL), then the combined organic layers are washed with water (50 mL), dried (MgSO ₄ ), and concentrated to give the title compound (9d) as a colourless crystalline solid, that is recrystallized from ethyl acetate to give colourless crystals: yield 9.97 g, 74.8%; mp 129-130 ⁰ C; R _F 0.36 on basic alumina (hexanes, ethyl acetate, methanol 96: 4: 0.4); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.26 - 1.31 (br s, 44H, 22 x CH ₂ ), 1.55 (pentet, 4H, J = 6.5 Hz, 2 OCH ₂ CH ₂ ), 2.97 (s, 6H, 2 x N(CH ₃ ) ₂ , 3.47 (t, 4H, J = 6.6 Hz, tetradecyl OCH ₂ ), 3.67 (s, 4H, OCH ₂ C), 3.82 (s, 4H, CH ₂ N), 11.88 (brs, HN); ¹³ C NMR δ 71.9 (CH ₂ CH ₂ OC), 66.9 (CCH ₂ OCH ₂ C), 58.6 (CH ₂ N), 47.7 (N(CH ₃ ) ₂ ), 44.7 (q C), 32.1 (CH ₂ CH ₂ CH ₃ ), 29.8, 29.6, 29.5, 29.5, (tetradecyl CH ₂ ), 26.4 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.3 (Me); HR ESI MS m/z calc for C ₃₇ H ₇₉ N ₂ O ₂ (M-2CI-H): 583.6142. Found: 583.6139. Example 1OA

Λ/,yV,Λ/,Λr,yV',Λr-hexamethyl-2,2-bis(octyloxymethyl) -1,3-propanediammonium diiodide (10a)

[00162] An aqueous NaOH solution (2 M, 30 mL) is added to salt 9a (Example 9A) (4.44 g, 9.1 mmol) and the resulting mixture is extracted with dichloromethane (3 x 50 mL). The combined extracts are washed with water and dried (MgSO ₄ ) and concentrated to give a colourless syrup, Λ/,/V,Λ/\ΛMetramethyl-2,2-bis(octyloxymethyl)-1 ,3- propanediamine: yield 2.45 g, 64.8%; R _F 0.39 on basic alumina (hexanes, ethyl acetate, methanol 96: 4: 0.4); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.26 -1.32 (br s, 2OH, 10 x CH ₂ ), 1.54 (pentet, 4H, J = 7.0 Hz, 2 OCH ₂ CH ₂ ), 2.26 (s, 12H, 2 x N(CH ₃ J ₂ ), 3.26 (s, 4H, 2 x NCH ₂ ), 3.26 (s, 4H, OCH ₂ C), 3.33 (t, J = 6.5 Hz, 4H, octyl OCH ₂ ); ¹³ C NMR δ 71.2 (CH ₂ CH ₂ OC), 70.8 (CCH ₂ OCH ₂ C), 59.9 (CH ₂ N), 48.7 (N(CH ₃ ) ₂ ), 45.8 (q C), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.9, 29.6, 29.5, (3 octyl CH ₂ ), 26.5 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.2 (Me). [00163] Methyl iodide (3.6 mL, 57.9 mmol, 10.0 eq) is added to a stirred solution of /V,N,ΛΛΛMetramethyl-2,2-bis(octyloxymethyl)-1 ,3-propanediamine (2.4 g, 5.79 mmol) in dry THF (15 mL) and the resulting solution is refluxed for 24 h, then concentrated. The title compound (10a), a light yellow crystalline solid, is recrystallized from ethyl acetate and acetone to give colourless crystals: yield 3.01 g, 74.5 %; mp 160-162 ⁰ C; R _F on basic alumina 0.53 (chloroform acetone methanol 2 1 1); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.27 - 1.29 (br s, 2OH, 1O x CH ₂ ), 1.60 (pentet, 4H, J = 6.6 Hz, 2 OCH ₂ CH ₂ ), 3.51 (t, 4H, J = 6.7 Hz, octyl OCH ₂ ), 3.65 (s, 18H, 6 x CH ₃ ), 3.91 (s, 4H, OCH ₂ C), 4.45 (s, 4H, CH ₂ N); ¹³ C NMR δ 72.2 (CH ₂ CH ₂ OC), 68.2 (CCH ₂ OCH ₂ C), 67.7 (CH ₂ N), 56.5 (N(CHa) ₃ ), 49.1(q C), 31.9 (CH ₂ CH ₂ CH ₃ ), 29.7, 29.4, 29.3, (octyl CH ₂ ), 26.4 (CH ₂ CH ₂ CH ₂ O), 22.7 (CH ₂ CH ₃ ), 14.2 (Me). HR ESI MS m/z calc for C ₂₇ H ₆₀ NIO ₂ (M-I): 571.3700, found: 571.3702; calc. for C ₅₄ H ₁₂₀ N ₄ I ₃ O ₄ (2M-I): 1269.6444, found: 1269.6443. Example 10B

2,2-Bis(decyloxymethyl)-Λ/,Λ/,Λ/,Λ/',Λ/',Λ/ ^I -hexamethyl-1,3-propanediammonium diiodide (10b)

[00164] An aqueous NaOH solution (2 M, 20 ml.) is added to salt 9b (Example 9B) (2.5 g, 4.37 mmol) then extracted with dichloromethane (3 x 25 ml_) following the procedure of Example 1OA to yield a colourless syrup of 2,2-bis(decyloxymethyl)-Λ/,Λ/,/V,Λ/ ¹ - tetramethyl-1 ,3-propanediamine, yield: 1.7 g, 79%; R _F 0.42 on basic alumina (hexanes, ethyl acetate, methanol 96: 4: 0.4); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.26 - 1.28 (br s, 28H, 14 x CH ₂ ), 1.54 (br m, 4H, 2 OCH ₂ CH ₂ ), 2.26 (s, 16H, 2 x N(CH ₃ ) ₂ , 2 x NCH ₂ ), 3.26 (s, 4H, OCH ₂ C), 3.38 (t, J = 6.5 Hz ₁ 4H, decyl OCH ₂ ); ¹³ C NMR δ 71.1 (CH ₂ CH ₂ OC), 70.7 (CCH ₂ OCH ₂ C), 59.9 (CH ₂ N), 48.6 (N(CH ₃ ) ₂ ), 45.6 (q C), 32.1 (CH ₂ CH ₂ CH ₃ ), 29.9, 29.8, 29.8, 29.7, 29.5, (decyl CH ₂ ), 26.5 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.2 (Me).

[00165] Methyl iodide (2.24 ml_, 36.1 mmol, 10 eq) is added to a stirred solution of 2,2- bis(decyloxymethyl)-Λ/,Λ/,ΛΛΛMetramethyl-1 ,3-propanediamine (1.7 g, 3.6 mmol) in dry THF (25 ml.) following the procedure of Example 1OA to give the title compound (10b) as a light yellow crystalline solid that is recrystallized from ether and acetone to give colourless crystals: yield 2.4 g, 73%; mp 75°C; R _F on basic alumina 0.57 (chloroform acetone methanol 2 1 1); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.26 -1.30 (br s, 28H, 14 x CH ₂ ), 1.60 (pentet, 4H, J = 6.5 Hz, 2 OCH ₂ CH ₂ ), 3.51 (t, 4H, J= 6.9 Hz, decyl OCH ₂ ), 3.65 (s, 18H, 6 x CH ₃ ), 3.91 (s, 4H, OCH ₂ C), 4.44 (s, 4H, CH ₂ N); ¹³ C NMR δ 71.9 (CH ₂ CH ₂ OC), 68.2 (CCH ₂ OCH ₂ C), 67.9 (CH ₂ N), 56.1 (N(CH ₃ ) ₃ ). 48.7 (q C), 31.7 (CH ₂ CH ₂ CH ₃ ), 29.45, 29.43, 29.37, 29.14 (4 decyl CH ₂ ), 29.25 (OCH ₂ CH ₂ ), 26.2 (CH ₂ CH ₂ CH ₂ O), 22.5 (CH ₂ CH ₃ ), 14.0 (Me); HR ESI-MS m/z calc. for C ₃ iH ₆₈ N ₂ IO ₂ ⁺ 627.4326 (M-I), found 627.4326; calc. for C ₆₂ H ₁₃₆ I ₃ N ₄ O ₄ ⁺ 1381.7696 (2M-I); found 1381.7694. Example 1OC

2,2-Bis(dodecyloxymethyl)-Λ/,Λ/,Λ/,Λ/',Λ/',Λ/'-hexa methyl-1,3-propanediammonium diiodide (10c)

₁ CH ₃

10c [00166] An aqueous NaOH solution (2 M, 50 ml_) is added to salt 9c (Example 9C) (4.75 g, 7.9 mmol) and the resulting solution is extracted with dichloromethane following the procedure of Example 1OA to yield a colourless syrup, 2,2-bis(dodecyloxymethyl)- Λ/,Λ/,ΛΛ/V-tetramethyl-1 ,3-propanediamine: yield 3.27 g, 78.4%; R _F 0.48 on basic alumina (hexanes, ethyl acetate, methanol 96: 4: 0.4); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.26 -1.33 (br s, 36H, 18x CH ₂ ), 1.53 (pentet, 4H, J = 7.0 Hz, 2 OCH ₂ CH ₂ ), 2.26 (2s, 16H, 2 x N(CHa) ₂ , 2 x NCH ₂ ), 3.26 (s, 4H, OCH ₂ C), 3.33 (t, J = 6.5 Hz, 4H, dodedecyl OCH ₂ ); ¹³ C NMR δ 71.2 (CH ₂ CH ₂ OC), 70.7 (CCH ₂ OCH ₂ C), 59.9 (CH ₂ N), 48.7 (N(CH ₃ ) ₂ ), 45.7 (q C), 32.1 (CH ₂ CH ₂ CH ₃ ),29.9, 29.8, 29.8, 29.7, 29.5 (dodecyl CH ₂ ), 26.5 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.3 (Me). [00167] Methyl iodide (3.9 ml_, 61.7 mmol, 10 eq) is added to a stirred solution of 2,2- bis(dodecyloxymethyl)-Λ/,Λ/,/V,ΛMetramethyl-1 ,3-propanediamine (3.25 g, 6.18 mmol) in dry THF (20 ml.) following the procedure of Example 1OA to give compound 10c as a light yellow crystalline solid that is recrystallized from ethyl acetate and acetone to give colourless crystals: yield 3.75 g, 75.5 %; R _F on basic alumina 0.48 (hexanes, ethyl acetate, methanol 96: 4: 0.4); mp 130-132 ⁰ C; ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9Hz, 2 x Me), 1.26 -1.30 (br s, 36H, 18x CH ₂ ), 1.59 (pentet ,4H ₁ J= 6.4 Hz, 2 OCH ₂ CH ₂ ), 3.51 (t, 4H, J = 6.7 Hz, dodecyl OCH ₂ ), 3.65 (s, 18H, 6 x CH ₃ ), 3.91 (s, 4H, OCH ₂ C), 4.45 (s, 4H, CH ₂ N); ¹³ C NMR δ 72.1 (CH ₂ CH ₂ OC), 68.2 (CCH ₂ OCH ₂ C), 67.9 (CH ₂ N), 56.4 (N(CH ₃ ) ₃ ), 48.9 (q C), 31.9(CH ₂ CH ₂ CH ₃ ), 29.6, 29.5, 29.4, 29.4, (dodecyl CH ₂ ), 26.3 (CH ₂ CH ₂ CH ₂ O), 22.7 (CH ₂ CH ₃ ), 14.1 (Me); LR ESI MS m/z calc for C ₃₅ H ₇₆ N ₂ IO ₂ 683.49, found 683.3 (M-I). Anal. CaIc. for C35H76N2O2I2: C 51.85, H 9.45, N 3.46. Found: C 51.43, H 9.32, N 3.71. Example 1OD

Λ/,Λ/,Λ/,Λ/ ^l ,Λ/',Λr-Hexamethyl-2,2-bis(tetradecyloxymethyl)-1,3- propanediammonium diiodide (1Od)

[00168] An aqueous NaOH solution (2 M, 40 mL) is added to salt 9d (Example 9D) (9.97 g, 15.2 mmol) and the resulting solution is extracted with dichloromethane (3 x 50 mL). The combined extracts are washed with water and dried (MgSO ₄ ) and concentrated to colourless syrup, /V,/V,ΛΛΛMetramethyl-2,2-bis(tetradecyloxymethyl)-1 ,3- propanediamine: yield 7.85 g, 65.9%; R _F 0.51 on basic alumina (hexanes, ethyl acetate, methanol 96: 4: 0.4); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.26 -1.31 (br s, 44H, 22 x CH ₂ ), 1.51 (pentet, 4H, J = 7.0 Hz, 2 OCH ₂ CH ₂ ), 2.26 (s, 16H, 2 x N(CH ₃ ) ₂ , 2 x NCH ₂ ), 3.26 (s, 4H, OCH ₂ C), 3.33 (t, J = 6.5 Hz, 4H, tetradecyl OCH ₂ ); ¹³ C NMR δ 71.2 (CH ₂ CH ₂ OC), 70.7 (CCH ₂ OCH ₂ C), 59.9 (CH ₂ N), 48.7 (N(CH ₃ ) ₂ ), 45.7 (q C), 32.1 (CH ₂ CH ₂ CH ₃ ), 29.91 , 29.86, 29.85, 29.82, 29.81 , 29.80, 29.65 (8 tetradecyl CH ₂ ), 29.52 (OCH ₂ CH ₂ ), 26.5 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.3 (Me); LR ESI MS: m/z calc for C ₃₇ H ₇₉ N ₂ O ₂ 583.61 , Found 583.5.

[00169] Methyl iodide (4.3 mL, 68.7 mmol, 10 eq) is reacted with Λ/.Λ/.ΛΛΛMetramethyl- 2,2-bis(tetradecyloxymethyl)-1 ,3-propanediamine (4.0 g, 6.87 mmol) in dry THF (20 mL) following the procedure of Example 1OA to give the title compound as a light yellow crystalline solid that is recrystallized from ethyl acetate and acetone to give colourless crystals: yield 5.7 g, 96%; R _F on basic alumina 0.63 (chloroform : acetone : methanol 2:1 :1); mp 127-128X; ¹ H NMR δ 0.88 ppm (t, 6H, J = 7.0 Hz, 2 x Me), 1.26 -1.30 (br s, 44H, 22 x CH ₂ ), 1.57 (pentet, 4H, J = 7.1 Hz, 2 OCH ₂ CH ₂ ), 3.50 (t, 4H, J = 6.8 Hz, tetradecyl OCH ₂ ), 3.63 (s, 18H, 6 x CH ₃ ), 3.93 (s, 4H, OCH ₂ C), 4.48 (s, 4H, CH ₂ N); ¹³ C NMR δ 72.2 (CH ₂ CH ₂ OC), 68.2 (CCH ₂ OCH ₂ C), 67.7 (CH ₂ N), 56.6 (N(CH ₃ ) ₃ ), 49.1 (q C), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.83, 29.80, 29.78, 29.78, 29.76, 29.54, 29.48 (8 tetradecyl CH ₂ ), 29.68 (OCH ₂ CH ₂ ), 26.5 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.23 (Me); LR ESI MS m/z calc for C ₃₉ H ₈₄ N ₂ O ₂ I (M-I) 739.56, found 739.3. Anal. CaIc. for C ₃₉ H ₈₄ N ₂ O ₂ I ₂ : C 54.03, H 9.77, N 3.23. Found: C 53.78, H 9.76, N 3.09. Example 11A 1,3-Bis(1-azacyclopentyl)-2,2-bis(octyloxymethyl)propane dihydrochloride (11a)

H ₃ C(

11a

[00170] A stirred solution of compound 8a (Example 8A) (18.0 g, 31.0 mmol) in pyrrolidine (100 mL) containing potassium carbonate (10.7 g, 31.0 mmol, 2.5 eq) is refluxed under nitrogen for 48 h, allowed to cool to rt, then filtered. The solid is washed with dichloromethane (2 x 10 mL) and the filtrate and washings are combined and diluted with dichloromethane (100 mL). The resulting solution is washed with water (3 x 100 mL), dried (MgSO ₄ ) and concentrated at 30 ⁰ C to give crude 1 ,3-bis(1-azacyclopentyl)- 2,2-bis(octyloxymethyl)propane: yield 14.20 g. This product is taken up in dichloromethane (100 mL) and the resulting solution is shaken with ice cold 2 M HCI (100 mL). The aqueous layer is extracted with dichloromethane (2 x 100 mL), then the combined organic layers are washed with water (20 mL), dried (MgSO ₄ ) and concentrated to give the title compound as a light yellow crystalline solid that is recrystallized from hexanes, ethyl acetate 2:1 to give colorless crystals: yield 12.5 g, 75 %; mp 124-125°C, R _F 0.22 on basic alumina (hexanes, ethyl acetate, methanol, 96:4:0.4); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.26-1.31 (br s, 2OH, 1O x CH ₂ ), 1.55 (pentet, 4H, J = 6.6 Hz, 2 OCH ₂ CH ₂ ), 2.06 (YY ¹ part of AA ¹ BB ¹ XX ¹ YY' pattern, 4H, 1/2 of 2 N(CH ₂ CH ₂ ),), 2.25 (XX ¹ part Of AA ¹ BB ¹ XX ¹ YY' pattern, 4H, 1/2 of 2 N(CH ₂ CH ₂ ) ₂ ), 3.21 (BB ¹ part Of AA ¹ BB ¹ XX ¹ YY' pattern, 4H, 1/2 of 2 N(CH ₂ )), 3.46 (t, 4H, J = 6.6 Hz, octyl OCH ₂ ), 3.59 (s, 4H, OCH ₂ C), 3.84 (s, 4H, CH ₂ N), 3.91 (AA ¹ part of AA ¹ BB ¹ XX ¹ YY ¹ pattern, 4H, 1/2 of 2 N(CH ₂ )), 11.51 (br s, HN); ¹³ C NMR δ 71.5 (CH ₂ CH ₂ OC), 67.5 (CCH ₂ OCH ₂ CH ₂ ), 57.8 (NCH ₂ ), 56.9 (CH ₂ N), 44.3 (q C), 31.7 (CH ₂ CH ₂ CH ₃ ), 29.41 , 29.25, 29.18 (3 octyl CH ₂ ), 26.2 (CH ₂ CH ₂ CH ₂ O), 23.5(NCH ₂ CH ₂ ), 22.6 (CH ₂ CH ₃ ), 14.0 (Me); HR ESI MS m/z calcd for C ₂₉ H ₅₉ N ₂ O ₂ (M-H-2CI) 467.4577, found 467.4578. Example 11 B

1 ,3-Bis(1 -azacyclopentyl)-2,2-bis(decyloxymethyl)propane dihydrochloride (11b)

H ₃ C( CH ₃

[00171] Treatment of a solution of compound 8b (Example 8B) (16.0 g, 25.0 mmol) in pyrrolidine (100 mL) containing potassium carbonate (8.69 g, 62.8 mmol, 2.5 eq) following the procedure of Example 11A gives a light brown syrup, 1 ,3-bis(1- azacyclopentyl)-2,2-bis(decyloxymethyl)propane: yield 11.93 g. Addition of ice cold 2 M HCI (100 mL) gives a light yellow crystalline solid that is recrystallized from ethyl acetate to give colorless crystals: yield 10.9 g, 76 %; mp 125-126°C, R _F 0.24 on basic alumina (hexanes, ethyl acetate, methanol, 96:4:0.4); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.8 Hz, 2 x Me), 1.26-1.28 (br s, 28H, 14 x CH ₂ ), 1.55 (pentet, 4H, J = 6.3 Hz, 2 OCH ₂ CH ₂ ), 2.05 (YY' part of AA'BB'XXΥY' pattern, 4H, 1/2 of 2 2 N(CH ₂ CH ₂ ) ₂ ), 2.25 (XX' part of AA ¹ BB ¹ XX ¹ YY' pattern, 4H, 1/2 of 2 2 N(CH ₂ CH ₂ ) ₂ ), 3.21 (BB ¹ part of AA ¹ BB ¹ XX ¹ YY ¹ pattern, 4H, N(CH ₂ ) ₂ ), 3.45 (t, 4H , J = 6.6 Hz, decyl OCH ₂ ), 3.58 (s, 4H, OCH ₂ C), 3.84 (s, 4H, CH ₂ N), 3.91 (BB ¹ part of AA ¹ BB ¹ XX ¹ YY' pattern, 4H, N(CH ₂ ) ₂ ), 11.5 (br s, HN); ¹³ C NMR δ 71.7 (CH ₂ CH ₂ OC), 67.5 (CCH ₂ O), 57.9 (NCH ₂ ), 57.0 ((CH ₂ ) ₂ N), 44.5 (q C), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.71 , 29.66, 29.59, 29.47, 29.40 (6 decyl CH ₂ ), 26.3 (CH ₂ CH ₂ CH ₂ O), 23.6 (N(CH ₂ CH ₂ ) ₂ ), 22.8 (CH ₂ CH ₃ ), 14.2 (Me); HR ESI MS m/z calcd for C ₃₃ H ₆₇ N ₂ O ₂ (M- H-2CI) 523.5203, found 523.5204. Example 11C

1 ,3-Bis(1 -azacyclopentyl^^-bisfdodecyloxymethyOpropane dihydrochloride (11c)

H ₃ C( CH ₃

[00172] Treatment of a solution of compound 8c (Example 8C) (12.2 g, 17.6 mmol) in pyrrolidine (10OmL) containing potassium carbonate (6.1 g, 44 mmol, 2.5 eq) following the procedure of Example 11A gives an orange syrup, 1 ,3-bis(1-azacyclopentyl)-2,2- bis(dodecyloxymethyl)propane: yield 12.9 g. Addition of ice cold 2 M HCI (100 mL) and dichloromethane (30 mL) provided a light pink crystalline solid that is dissolved in dichloromethane (30 mL). The dichloromethane solution is washed with distilled water (10 mL), dried (MgSO ₄ ) and concentrated to a crystalline solid that is recrystallized from ethyl acetate to give colorless crystals: yield 8.8 g, 77 %; mp 127°C; R _F 0.28 on basic alumina (hexanes, ethyl acetate, methanol, 96:4:0.4); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.26-1.28 (br s, 36H, 18xCH ₂ ), 1.55 (pentet, 4H, J = 6.4 Hz, 2 OCH ₂ CH ₂ ), 2.06 (YY ¹ part Of AA ¹ BB ¹ XX ¹ YY' pattern, 4H, 1/2 of 2 2 N(CH ₂ CH ₂ ) ₂ ), 2.25 (XX' part of AA ¹ BB ¹ XX ¹ YY ¹ pattern, 4H, 1/2 of 2 2 N(CH ₂ CH ₂ ),), 3.21 (BB ¹ part of AA ¹ BB ¹ XX ¹ YY' pattern, 4H, N(CH ₂ ) ₂ ), 3.45 (t, 4H, J = 6.5 Hz , dodecyl OCH ₂ ), 3.58 (s, 4H, OCH ₂ C), 3.83 (s, 4H, CH ₂ N), 3.91 (AA ¹ part of AA'BB'XX'YY' pattern, 4H, N(CH ₂ ) ₂ ), 11.5 (br s, HN); ¹³ C NMR δ 71.7 (CH ₂ CH ₂ OC), 67.6 (CCH ₂ O), 58.0 (NCH ₂ ), 57.1 ((CH ₂ J ₂ N) ₁ 44.5 (q C), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.7, 29.6, 29.5, 29.4, (dodecyl CH ₂ ), 26.3 (CH ₂ CH ₂ CH ₂ O), 23.6

(N(CH ₂ CH ₂ ) ₂ ), 22.8 (CH ₂ CH ₃ ), 14.2 (Me); HR ESI MS m/z calcd for C ₃₇ H ₇₅ N ₂ O ₂ (M-H- 2Cl) 579.5829, found 579.5826.

Example 11D

1 ,3-Bis(1 -azacyclopentyl)-2,2-bis(tetradecyloxymethyl)propane dihydrochloride (11d)

H ₃ C( ₃ CH ₃

[00173] Treatment of a solution of compound 8d (Example 8D) (14.96 g, 31.29 mmol) in pyrrolidine (100 mL) containing potassium carbonate (10.78 g, 78.0 mmol, 2.5 eq) following the procedure of Example 11A gives a brown solid, 1 ,3-bis(1-azacyclopentyl)- 2,2-bis(tetradecyloxymethyl)propane, yield 17.26 g. Addition of ice cold 2 M HCI (100 mL) and dichloromethane (30 mL) provided a yellow crystalline solid (18.11 g) that is dissolved in dichloromethane (30 mL). The solution is dried (MgSO ₄ ) and concentrated to colorless crystalline solid that is recrystallized from ethyl acetate to give the title compound as colorless crystals: yield 17.5 g, 79 %; mp 128 ⁰ C; R _F 0.33 on basic alumina (hexanes, ethyl acetate, methanol, 96:4:0.4); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.26-1.28 (br s, 44H, 22 x CH ₂ ), 1.55 (pentet, 4H, J = 6.3 Hz, 2 OCH ₂ CH ₂ ), 2.05 (YY' part of AA'BB'XX'YY ¹ pattern, 4H, 1/2 of 2 2 N(CH ₂ CH ₂ ) ₂ ), 2.25 (XX' part of AA'BB'XX'YY' pattern, 4H, 1/2 of 2 2 N(CH ₂ CH ₂ ) ₂ ), 3.21 (BB ¹ part of AA ¹ BB ¹ XX ¹ YY ¹ 5 pattern, 4H, N(CH ₂ ) ₂ ), 3.45 (t, 4H, J = 6.5 Hz , tetradecyl OCH ₂ ), 3.58 (s, 4H, OCH ₂ C), 3.84 (s, 4H, CH ₂ N), 3.91 (AA ¹ part of AA'BB'XX'YY' pattern, 4H, N(CH ₂ J ₂ ), 11.5 (br s, HN); ¹³ C NMR δ 71.7 (CH ₂ CH ₂ OC), 67.6 (CCH ₂ O), 58.0 (NCH ₂ ), 57.1 ((CH ₂ ) ₂ )N), 44.6 (q C), 32.1 (CH ₂ CH ₂ CH ₃ ), 29.83, 29.82, 29.79, 29.65, 29.57, 29.49 (8 tetradecyl CH ₂ ), 26.4 (CH ₂ CH ₂ CH ₂ O), 23.7 (N(CH ₂ CH ₂ ) ₂ ), 22.8 (CH ₂ CH ₃ ), 14.2 (Me); HR ESI MS m/z calcd for 10 C _4I H ₈₃ N ₂ O ₂ (M-H-2CI) 635.6455, found 635.6454.

Example 12A

1 ,3-bis(1 -methyl-1 -azoniacyclopentyl)-2,2-bis(octyloxymethyl)propane diiodide (12a)

H ₃ C(

15 [00174] An aqueous 2 M NaOH solution (50 ml_) is added to compound 11a (Example 11A) (12.5 g, 23.2 mmol) and the resulting mixture is extracted with dichloromethane (3 x 50 mL). The combined extracts are washed with water and dried (MgSO ₄ ), and concentrated to give the free base, 1 ,3-bis(1-azacyclopentyl)-2,2- bis(octyloxymethyl)propane as a light yellow syrup: yield 10.3 g, 72%; R _F 0.32 on basic

20 alumina (hexanes, ethyl acetate, methanol, 96:4:0.4); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.8 Hz, 2 x Me), 1.27-1.34 (br s, 2OH, 1O x CH ₂ ), 1.53 (pentet, 4H, J = 6.7 Hz, 2 OCH ₂ CH ₂ ), 1.68 (m, 8H, 2NCH ₂ CH ₂ ), 2.48 (s ,4H CH ₂ N), 2.56 (m, 8H, 2N(CH ₂ ) ₂ , 3.27 (s, 4H, OCH ₂ C), 3.32 (t, 4H, J = 6.4 Hz, octyl OCH ₂ ); ¹³ C NMR δ 71.7 (CCH ₂ OCH ₂ CH ₂ ), 71.1 (CH ₂ CH ₂ OC), 56.81 (CH ₂ N), 56.84 (NCH ₂ ), 45.7 (q C), 31.9 (CH ₂ CH ₂ CH ₃ ), 29.87, 29.55,

25 29.43 (3 octyl CH ₂ ), 26.4 (CH ₂ CH ₂ CH ₂ O), 24.3 (NCH ₂ CH ₂ ), 22.8 (CH ₂ CH ₃ ), 14.1 (Me).

[00175] Methyl iodide (13.3 g, 21.3 mmol, 10 eq) is added to a stirred solution of 1 ,3- bis(1-azacyclopentyl)-2,2-bis(octyloxymethyl)propane (9.90 g, 21.3 mmol) in dry THF (50 mL). The resulting mixture is refluxed under nitrogen for 48 h, then concentrated. The title compound, a light brown crystalline solid, is recrystallized from ethyl acetate to give colorless crystals: yield 13 g, 81 %; mp 92°C; R _F 0.69 on basic alumina (chloroform, acetone, methanol, ammonia 2:2:1 :0.5); ¹ H NMR δ 0.89 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.26-1.30 (br s, 2OH, 1O x CH ₂ ), 1.57 (pentet, 4H, J = 6.5 Hz, 2 OCH ₂ CH ₂ ), 2.18 (YY' part of AA'BB'XX'YY' pattern, 4H, 1/2 of 2 2 N(CH ₂ CHz) ₂ ), 2.38 (XX ¹ part of AA'BB'XX'YY' pattern, 4H, 1/2 of 2 2 N(CH ₂ CH ₂ ),)), 3.46 (s, 6H, 2 NCH ₃ ), 3.49 (t, 4H, J = 6.6 Hz , octyl OCH ₂ ), 3.96 (s, 4H, OCH ₂ C), 4.04 (m, 8H, 2 N(CH ₂ J ₂ ). 4.63 (s, 4H, 2 CH ₂ N); ¹³ C NMR δ 71.9 (CH ₂ CH ₂ OC), 68.3 (CCH ₂ OCH ₂ CH ₂ ), 66.9 (NCH ₂ ), 65.4 (CH ₂ N), 48.5 (CH ₃ N), 48.4 (q C), 31.8 (CH ₂ CH ₂ CH ₃ ), 29.5, 29.3, 29.2 (3 octylCH ₂ ), 26.3 (CH ₂ CH ₂ CH ₂ O), 22.6 (CH ₂ CH ₃ ), 21.1 (NCH ₂ CH ₂ ), 14.1 (Me); HR ESI-MS m/z calcd for C ₃₁ H ₆₄ IN ₂ O ₂ 623.4013 (M-I), found 623.4011.

Example 12B

2,2-Bis(decyloxymethyl)-1 ,3-bis(1 -methyl-1 -azoniacyclopentyl)propane diiodide (12b)

Pi ₃ C( CH ₃

[00176] Aqueous 2 M NaOH solution (50 ml.) and compound 11b (Example 11 B) (10.9 g, 18.3 mmol) are reacted following the procedure of Example 12A to give a colorless syrup, 1 ,3-bis(1-azacyclopentyl)-2,2-bis(decyloxymethyl)propane: yield 9.5O g, 72.5%; R _F 0.34 on basic alumina (hexanes, ethyl acetate, methanol, 96:4:0.4); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.26-1.31 (br s, 28H, 14 x CH ₂ ), 1.53 (pentet, 4H, J = Hz, 2 OCH ₂ CH ₂ ), 1.68 (m, 8H, 2 N(CH ₂ CH ₂ )), 2.49 (s , 4H, NCH ₂ C, 2.57 (m , 8H, 2 N(CH ₂ ) ₂ ), 3.29 (s, 4H, OCH ₂ C), 3.33 (t, 4H, J = 6.5 Hz, decyl OCH ₂ ); ¹³ C NMR δ 71.9 (CCH ₂ OCH ₂ CH ₂ ), 71.3 (CH ₂ CH ₂ OC), 57.2 (CH ₂ N), 57.0 (N(CH ₂ ) ₂ ), 45.8 (q C), 32.1 (CH ₂ CH ₂ CH ₃ ), 29.93, 29.85, 29.78 29.68, 29.52 (6 decyl CH ₂ ), 26.5 (CH ₂ CH ₂ CH ₂ O), 24.4 (N(CH ₂ CH ₂ ) ₂ ), 22.8 (CH ₂ CH ₃ ), 14.3 (Me).

[00177] Methyl iodide (16.6 g, 117 mmol, 10 eq) and 1 ,3-bis(1-azacyclopentyl)-2,2- bis(decyloxymethyl)propane (6.1 g, 11.6 mmol) in dry THF (50 ml_) are treated following the procedure of Example 12A to give a light brown crystalline solid that is recrystallized from ethyl acetate to give an off white crystalline solid: yield 6.0 g, 81%; mp 95 - 96°C; R _F 0.71 on basic alumina (chloroform, acetone, methanol, ammonia 2:2:1 :0.5); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.26-1.30 (br s, 28H, 14 x CH ₂ ), 1.57 (pentet, 4H, J = 6.5 Hz, 2 OCH ₂ CH ₂ ), 2.18 (YY' part of AA ¹ BB ¹ XX ¹ YY' pattern, 4H, 1/2 of 2 2 N(CH ₂ CH ₂ ) ₂ ), 2.38 (XX ¹ part Of AA ¹ BB ¹ XX ¹ YY' pattern, 4H, 1/2 of 2 2 N(CH ₂ CH ₂ ),)), 3.46 5 (s, 6H, 2 NCH ₃ ), 3.49 (t, 4H, J = 6.6 Hz , decyl OCH ₂ ), 3.96 (s, 4H, OCH ₂ C), 4.04 (m , 8H, 2N(CH ₂ ) ₂ ), 4.63 (s, 4H, 2 CH ₂ N); ¹³ C NMR δ 72.1 (CH ₂ CH ₂ OC), 68.2 (CCH ₂ OCH ₂ CH ₂ ), 66.9 (NCH ₂ ), 65.2 (CH ₂ N), 48.6 (CH ₃ N), 48.3 (q C), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.71 , 29.67, 29.66, 29.47, 29.39 (5 decyl CH ₂ ), 26.5 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 21.2 (NCH ₂ CH ₂ ), 14.2 (Me); LR ESI MS m/z calcd for C ₃₅ H ₇₂ IN ₂ O ₂ (M-I) 10 679.64, found 679.3, calcd for (M-2I) 276.3, found 276.3. Anal. Calcd. for C ₃₅ H ₇₂ I ₂ N ₂ O ₂ : C, 52.11 , H, 9.00, N, 3.47. Found: C, 52.08, H, 9.17, N, 3.69.

Example 12C

2,2-Bis(dodecyloxymethyl)-1,3-bis(1-methyl-1-azoniacyclop entyl)propane diiodide (12c)

[00178] Reaction of 2 M NaOH (50 ml_) with salt 11c (Example 11C) (8.8 g, 13.5 mmol) following the procedure of Example 12A gives 1 ,3-bis(1-azacyclopentyl)-2,2- bis(dodecyloxymethyl)propane as a colorless syrup: yield 7.5 g, 74%; R _F 0.36 on basic alumina (hexanes, ethyl acetate, methanol, 96:4:0.4); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 20 Hz, 2 x Me), 1.26-1.31 (br s, 36H, 18 x CH ₂ ), 1.53 (pentet, 4H, J = 7.0 Hz, 2 OCH ₂ CH ₂ ), 1.69 (m, 8H, 2 N(CH ₂ CH ₂ ),), 2.49 (s, 4H, CH ₂ N), 2.57 (m, 8H , 2 N(CH ₂ J ₂ ), 3.28 (s, 4H, OCH ₂ C), 3.33 (t, 4H, J = 6.5 Hz , dodecyl OCH ₂ ); ¹³ C NMR δ 71.9 (CCH ₂ O), 71.3 (CH ₂ CH ₂ OC), 57.3 (CH ₂ N), 57.0 (N(CH ₂ J ₂ ), 45.8 (q C), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.3, 29.8, 29.7 (dodecyl CH ₂ ), 26.4 (CH ₂ CH ₂ CH ₂ O), 24.2 (N(CH ₂ CH ₂ ) ₂ ) _, 22.9 (CH ₂ CH ₃ ), 14.3 (Me).

25 [00179] Methyl iodide (8 ml_, 129.7 mmol, 10 eq) is reacted with 1 ,3-bis(1- azacyclopentyl)-2,2-bis(dodecyloxymethyl)propane (7.5 g, 13 mmol) in dry THF (50 mL) following the procedure of Example 12A to give the title compound, as an offwhite crystalline solid, that is recrystallized from ethyl acetate to give colorless crystals: yield 7.5 g, 84%; mp 100-101 ⁰ C; R _F 0.74 on basic alumina (chloroform, acetone, methanol, ammonia 2:2:1 :0.5); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.25-1.23 (br s, 36H, 18 x CH ₂ ), 1.57 (pentet, 4H, J = 6.6 Hz, 2 OCH ₂ CH ₂ ), 2.17 (YY' part of AA'BB'XX'YY' pattern, 4H, 1/2 of 2 2 N(CH ₂ CH ₂ J ₂ ), 2.38 (XX' part of AA ¹ BB ¹ XX ¹ YY' pattern, 4H, 1/2 of 2 2 N(CH ₂ CH ₂ J ₂ ), 3.45 (s, 2 NCH ₃ ), 3.49 (t, 4H , J = 6.6 Hz , 2 dodecyl OCH ₂ ), 3.96 (s, 4H, OCH ₂ C), 4.05 (m , 8H , NCH ₂ ), 4.64 (s, 4H, CH ₂ N); ¹³ C NMR δ 71.9 (CH ₂ CH ₂ OC), 68.3 (CCH ₂ OCH ₂ CH ₂ ), 66.9 (NCH ₂ ), 65.5 (CH ₂ N) , 48.4 (CH ₃ N), 48.3 (q C), 31.8 (CH ₂ CH ₂ CH ₃ ), 29.6, 29.5, 29.3, 29.3 (dodecyl CH ₂ ), 26.3 (CH ₂ CH ₂ CH ₂ O), 22.6 (CH ₂ CH ₃ ), 21.1 (NCH ₂ CH ₂ ), 14.0 (Me); LR ESI MS m/z calcd for C ₃₉ H ₈₀ IN ₂ O ₂ (M-I) 735.53, found 735.3; calcd for C ₃₈ H ₇₇ N ₂ O ₂ (M-2I-Me) 593.60, found 593.4; calcd for (M- 2l)/2 304.31 , found 304.3. Anal. Calcd. for C ₃₉ H ₈₀ I ₂ N ₂ O ₂ : C, 54.29, H, 9.34, N, 3.47. Found: C, 54.16, H, 9.77, N, 3.38.

Example 12D

1 ,3-Bis(1 -methyl-1 -azoniacyclopentyl)-2,2-bis(tetradecyloxymethyl)propane iodide (12d)

H ₃ C(H ₃ CH ₃

[00180] Reaction of 2 M NaOH (50 mL) with salt 11d (Example 11D) (17.5 g, 24.7 mmol) following the procedure of Example 12A gives 1 ,3-bis(1-azacyclopentyl)-2,2- bis(tetradecyloxymethyl)propane as a light yellow crystalline solid: yield 14.3 g, 72 %; mp 100-102 ⁰ C; R _F 0.38 on basic alumina (hexanes, ethyl acetate, methanol, 96:4:0.4); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.26-1.31 (br s, 44H, 22 x CH ₂ ), 1.53 (pentet, 4H, J = 7.0 Hz, 2 OCH ₂ CH ₂ ), 1.68 (m, 8H, 2 N(CH ₂ CH ₂ ),), 2.49 (s, 4H, CH ₂ N), 2.57 (m, 8H, 2 N(CH ₂ ) ₂ ), 3.28 (s, 4H, OCH ₂ C), 3.33 (t, 4H, J = 6.5 Hz , tetradecyl OCH ₂ ); ¹³ C NMR δ 71.7 (CCH ₂ O), 71.1 (CH ₂ CH ₂ OC), 57.1 (CH ₂ N), 56.9 (N(CH ₂ J ₂ ), 45.6 (q C), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.80, 29.74, 29.70 29.55, 29.40 (8 tetradecyl CH ₂ ), 26.4 (CH ₂ CH ₂ CH ₂ O), 24.2 (N(CH ₂ CH ₂ ) ₂ ) _, 22.7 (CH ₂ CH ₃ ), 14.1 (Me).

[00181] Methylation of 1 ,3-bis(1-azacyclopentyl)-2,2-bis(tetradecyloxymethyl)propane (7.15 g, 11.3 mmol) in THF (5O mL) with methyl iodide (15.8 g, 112 mmol, 10 eq) following the procedure of Example 12A gives the title compound, a light brown crystalline solid, that is recrystallized from ethyl acetate to give an off-white crystalline solid: yield 7.6 g, 94%; mp 108 ⁰ C; R _F 0.76 on basic alumina (chloroform, acetone, methanol, ammonia 2:2:1 :0.5); ¹ H NMR δ 0.88 ppm (t, 6H, J = 6.9 Hz, 2 x Me), 1.26-1.29 (br s, 44H, 22 x CH ₂ ), 1.57 (pentet, 4H, J = 6.5 Hz, 2 OCH ₂ CH ₂ ), 2.17 (YY' part of AA ¹ BB ¹ XX ¹ YY' pattern, 4H, 1/2 of 2 2 N(CH ₂ CH ₂ ) ₂ ), 2.38 (XX ¹ part of AA ¹ BB ¹ XX ¹ YY ¹ pattern, 4H, 1/2 of 2 2 N(CH ₂ CH ₂ ) ₂ ), 3.45 (s, 2 NCH ₃ ), 3.49 (t, 4H ₁ J = 6.6 Hz, tetradecyl OCH ₂ ), 3.97 (s, 4H, OCH ₂ C), 4.05 (m , 8H , NCH ₂ ), 4.67 (s, 4H, CH ₂ N); ¹³ C NMR δ 72.0 (CH ₂ CH ₂ OC), 68.3 (CCH ₂ OCH ₂ CH ₂ ), 66.9 (NCH ₂ ), 65.3 (CH ₂ N) , 48.6 (CH ₃ N), 48.3 (q C), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.72, 29.69, 29.62, 29.44, 29.39 (5 tetradecyl CH ₂ ), 26.4 (CH ₂ CH ₂ CH ₂ O), 22.7 (CH ₂ CH ₃ ), 21.2 (NCH ₂ CH ₂ ), 14.2 (Me); LR ESI MS m/z calcd for C ₄₃ H ₈₈ IN ₂ O ₂ (M-I) 791.59, found 791.3; calcd for M/2: 332.34, found 332.4; calcd for C ₈₆ H ₁₇₆ I ₃ N ₄ O ₄ (2 M -I) 1710.1 , found 1709.3. Anal. Calcd for C ₄₃ H ₈₈ I ₂ N ₂ O ₂ . H ₂ O: C, 55.12, H, 9.68, N, 2.99. Found: C, 55.26, H, 9.46, N, 3.30.

Example 13A 3,3-bis(octyloxymethyl)pentanedinitrile (13a)

1 ^3a

[00182] Potassium cyanide (0.80 g, 12.0 mmol, 3.0 eq) is added to a stirred solution of compound 8a (Example 8A) (2.4 g, 4.1 mmol) in dry DMF (25 ml_). The resulting mixture is stirred at 80°C for 24 h, and then allowed to cool to rt. A solid is deposited and the solution is decanted. The solid is washed with dichloromethane (2 x 10 ml_). The combined solution and washings are concentrated to give a yellow oil that is taken up in dichloromethane (30 mL). The resulting solution is washed with water (3 x 25 ml_), dried (MgSO ₄ ) and concentrated to give the title compound as a light yellow oil: yield 1.3 g, 83%; R _F 0.42 (hexanes: ethyl acetate 9:1); ¹ H NMR δ 0.88 (t, 6H, J = 6.9 Hz, 2 x Me), 1.23-1.33 (br s, 2OH, 10 x CH ₂ ), 1.55 (pentet, 4H, J = 7.0 Hz, 2 OCH ₂ CH ₂ ), 2.57 (s, 4H, CH ₂ CN), 3.42 (s, 4H, OCH ₂ C), 3.44 (t, J = 6.5 Hz, 4H, octyl OCH ₂ ); ¹³ C NMR δ 116.7 (CN), 71.9 (CH ₂ CH ₂ OC), 70.8 (CCH ₂ OCH ₂ C), 41.3 (q C), 32.9 (CH ₂ CH ₂ CH ₃ ), 29.45, 29.34 (2 octyl CH ₂ ), 29.47 (OCH ₂ CH ₂ ), 26.2 (CH ₂ CH ₂ CH ₂ O), 22.7 (CH ₂ CH ₃ ), 21.7 (CH ₂ CN) 14.2 (Me); HR ESI MS m/z calcd for C ₂₃ H ₄₂ N ₂ O ₂ Na (M+Na) 401.3138, found 401.3152. Example 13B 3,3-Bis(decyloxymethyl)pentanedinitrile (13b)

13b

[00183] Treatment of compound 8b (Example 8B) (5.9 g, 9.3 mmol) in dry DMF (30 ml.) 5 with potassium cyanide (1.8 g, 28.0 mmol, 3.0 eq ) following the procedure of Example 13A gives the title compound as a light yellow oil: yield 3.6 g, 91 %; R _F 0.46 (hexanes: ethyl acetate 9:1); ¹ H NMR δ 0.88 (t, 6H, J = 6.9 Hz, 2 x Me), 1.26-1.31 (br s, 28H, 14 x CH ₂ ), 1.53 (pentet, 4H, J = 7.2 Hz, 2 OCH ₂ CH ₂ ), 2.58 (s, 4H, CH ₂ N ₃ ), 3.43 (s, 4H, OCH ₂ C), 3.45 (t, 4H, J = 6.5 Hz, decyl OCH ₂ ); ¹³ C NMR δ 116.8 (CN), 72.0 (CH ₂ CH ₂ OC), 10 70.9 (OCH ₂ C), 41.3 (q C), 32.1 (CH ₂ CH ₂ CH ₃ ), 29.75, 29.72, 29.53, 29.47 (4 decyl CH ₂ ), 29.55 (OCH ₂ CH ₂ ), 26.2 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 21.7 (CH ₂ CN) 14.3 (Me); HR ESI MS m/z calcd for C ₂₇ H ₅₀ N ₂ O ₂ Na (M+Na) 457.3764, found 457.3781.

Example 13C 3,3-Bis(dodecyloxymethyl)pentanedinitrile (13c)

H ₃ C(H ₂ C) _{1 1} O 0(CH ₂ J _{1 1} CH ₃

15 ^13C

[00184] Treatment of compound 8c (Example 8C) (2.3 g, 3.3 mmol) in dry DMF (30 mL) with potassium cyanide (0.5 g, 8.4 mmol, 3.0 eq) following the procedure of Example 13A gives the title compound as a light yellow oil: yield 1.5 g, 91 %; R _F 0.49 (hexanes: ethyl acetate 9:1); ¹ H NMR δ 0.88 (t, 6H, J = 6.9 Hz, 2 x Me), 1.26-1.32 (br s, 36H, 18 x

20 CH ₂ ), 1.54-1.58 (pentet, 4H, J = 7.0 Hz, 2 OCH ₂ CH ₂ ), 2.57 (s, 4H, CH ₂ CN), 3.38 (s, 4H, OCH ₂ C), 3.45 (t, 4H, J = 7.0 Hz, 2 OCH ₂ CH ₂ ), 2.57 (s, 4H, CH ₂ CN), 3.38 (s, 4H, OCH ₂ C), 3.45 (t, 4H, J = 6.5 Hz, dodecyl OCH ₂ ); ¹³ C NMR δ 116.7 (CN), 72.0 (CH ₂ CH ₂ OC), 70.8 (CCH ₂ OCH ₂ C), 41.3 (q C), 32.0 (CH ₂ CH ₂ CH ₃ ), 2 x 29.72, 2 x 29.70, 29.51 , 29.45 (6 dodecyl CH ₂ ), 29.53 (OCH ₂ CH ₂ ), 26.2 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ),

25 21.7 (CH ₂ CN) 14.3 (Me); HR ESI MS m/z calcd for C ₃₁ H ₅₈ N ₂ O ₂ Na (M+Na) 513.4391 , found 513.4373. Example 13D 3,3-Bis(tetradecyloxymethyl)pentanedinitrile (13d)

13d

[00185] Treatment of compound 8d (Example 8D) (5.0 g, 6.7 mmol) in dry DMF (30 ml_) with potassium cyanide (1.0 g, 16.7 mmol, 2.5 eq) following the procedure of Example 13A gives a light yellow oil that is taken up in hot 95% ethanol (50 ml_). When this solution is kept at 5°C, the title compound (13d) precipitates as an amorphous solid, yield 2.24 g. Flash column chromatography of the residue yields an additional 0.57 g, total yield 2.81 g, 77%: R _F 0.56 (hexanes: ethyl acetate 9:1); mp 33-35°C' ¹ H NMR δ 0.88 (t, 6H, J = 6.8 Hz, 2 x Me), 1.22-1.36 (br s, 44H, 22 x CH ₂ ), 1.56 (pentet, 4H, J = 6.7 Hz, 2 OCH ₂ CH ₂ ), 2.58 (s, 4H, CH ₂ CN), 3.43 (s, 4H ₁ OCH ₂ C), 3.45 (t, J = 6.5 Hz, 4H, tetradecyl OCH ₂ ); ¹³ C NMR δ 116.7 (CN), 72.0 (CH ₂ CH ₂ OC), 70.8 (CCH ₂ OCH ₂ C), 41.3 (q C), 32.1 (CH ₂ CH ₂ CH ₃ ), 29.84, 29.78, 29.76, 29.72, 29.54, 29.51 (8 tetradecyl CH ₂ ), 29.56 (OCH ₂ CH ₂ ), 26.2 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 21.8 (CH ₂ CN) 14.3 (Me); HR ESI MS m/z calcd for C ₃₅ H ₆₆ N ₂ O ₂ Na (M+Na) 569.5017, found 569.5002.

Example 14A 3,3-bis(octyloxymethyl)pentanedioic acid (14a)

H ₃ C(

[00186] A mixture of compound 13a (Example 13A) (2.5 g, 5.61 mmol) in 1-propanol (40 ml_) containing 35% NaOH (10 mL) is refluxed for 36 h. The reaction mixture is concentrated then the resulting aqueous reaction mixture is refluxed for another 24 h. The reaction mixture is cooled to 10°C and acidified by adding a dilute HCI solution until the pH is 5 (pH paper). The mixture is extracted with ethyl acetate (2 x 50 mL) and the combined organic layers are washed with water (2 x 30 mL), brine (20 mL), dried (Na ₂ SO ₄ ), and concentrated to give the crude product (2.5). The product is purified by flash column chromatography on silica gel using a gradient changing from 5% EtOAc in hexanes to 15% EtOAc in hexanes as eluent to give as a thick colorless syrup: yield 1.75 g (63%); R _F 0.5 (EtOAc: hexanes 1 :1); ¹ H NMR (CDCI ₃ ) δ 0.88 (t, 6H, J = 6.5 Hz, CH ₃ ), 1.24-1.31 (m, 2OH, 10 x CH ₂ ), 1.53 (pentet, 4H, J = 6.5 Hz, OCH ₂ CH ₂ ), 2.61 (s, 4H, COCH ₂ ), 3.40 (t, 4H, J = 6.5, OCH ₂ ), 3.46 (s, 4H, OCH ₂ ), 10.92(bs, 2H, COOH); ¹³ C NMR (CDCI ₃ ) δ 176.8 (COOH), 73.2 (CCH ₂ O), 71.8 (OCH ₂ CH ₂ ), 41.1 (q C), 37.5

(HOOCCH ₂ ), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.60, 29.55, 29.42 (3 octyl CH ₂ ), 26.3 (OCH ₂ CH ₂ CH ₂ ), 22.8 (CH ₃ CH ₂ ), 14.2 (CH ₃ ); HR ESI MS m/z calcd for C ₂₃ H ₄₃ O ₆ (M-H) 415.3065, found 415.3042.

Example 14B 3,3-Bis(decyloxymethyl)pentanedioic acid (14b)

H ₃ C( CH ₃

[00187] Reaction of compound 13b (Example 13B) (2.5 g, 5.8 mmol) in 1-propanol (40 ml_) containing 35% NaOH (10 ml.) following the procedure of Example 14A gives the title compound as a colorless solid: yield 1.2 g (44%); mp 68-71 ⁰ C ¹ R _F 0.4 (EtOAc: hexanes 1 :1); ¹ H NMR (CDCI ₃ ) δ 0.87 (t, 6H, J = 6.5 Hz, CH ₃ ), 1.23-1.32 (m, 28H, 14 x CH ₂ ), 1.53 (pentet, 4H, J = 6.5 Hz, OCH ₂ CH ₂ ), 2.60 (s, 4H, COCH ₂ ), 3.41 (t, 4H, J = 6.5, OCH ₂ ), 3.47 (s, 4H, OCH ₂ ), 10.50(bs, 2H, COOH); ¹³ C NMR CDCI ₃ δ 176.4 (COOH), 73.2 (CCH ₂ O), 71.8 (OCH ₂ CH ₂ ), 41.1 (q C), 37.6 (HOOCCH ₂ ), 32.1 (CH ₂ CH ₂ CH ₃ ), 3 x 29.75, 29.60, 29.49 (5 decyl CH ₂ ), 26.3 (OCH ₂ CH ₂ CH ₂ ), 22.8 (CH ₃ CH ₂ ), 14.3 (CH ₃ ); HR ESI MS m/z calcd for C ₂₇ H ₅₂ O ₆ (M-H) 471.3691 , found 471.3667.

Example 14C 3,3-Bis(dodecyloxymethyl)pentanedioic acid (14c)

H ₃ C( _{1 1} CH ₃

[00188] A mixture of compound 13c (Example 13C) (2.5 g, 5.8 mmol) in 1-propanol (40 mL) containing 35% NaOH (10 mL) is treated following the procedure of Example 14A except that the aqueous mixture is refluxed for 36 h to give the product as a colorless solid: yield 2.2 g (46%); mp 80-82 ⁰ C; R _F 0.46 (ethyl acetate: hexanes 1 :1); ¹ H NMR (CDCI ₃ ) δ 0.88 (t, 6H, J = 6.5 Hz, CH ₃ ), 1.24-1.32 (m, 36H, 18 x CH ₂ ), 1.53 (pentet, 4H, J = 6.5 Hz, OCH ₂ CH ₂ ), 2.60 (s, 4H, COCH ₂ ), 3.40 (t, 4H, J = 6.5 Hz, OCH ₂ ), 3.46 (s, 4H ₁ OCH ₂ ), 10.6(bs,2H,COOH); ¹³ C NMR (CDCI ₃ ) δ 176.5 (COOH), 73.2 (CCH ₂ O), 71.8 5 (OCH ₂ CH ₂ ), 41.1 (qC), 37.6 (HOOCCH ₂ ), 32.1 (CH ₂ CH ₂ CH ₃ ), 3 x 29.84, 2 x 29.81 , 29.61 , 29.52 (7 dodecyl CH ₂ ), 26.3 (OCH ₂ CH ₂ CH ₂ ), 22.8 (CH ₃ CH ₂ ), 14.3 (CH ₃ ); HR ESI MS m/z calcd for C ₃₁ H ₅₉ O ₆ (M-H) 527.4317, found 527.4324.

Example 14D

3,3-Bis (tetradecyloxymethyOpentanedioic acid (14d)

H ₃ C( ) ₁₃ CH ₃

10

[00189] A mixture of compound 13d (Example 13D) (5.0 g, 6.7 mmol) in 1-propanol (40 ml.) containing 35% NaOH (10 ml_) is treated following the procedure of Example 14C to give the product as a colorless solid: yield: 2.2 g (46%); mp 84-86 ⁰ C; R _F 0.51 (ethyl acetate: hexanes 1 :1); ¹ H NMR (CDCI ₃ ) δ 0.88 (t, 6H, J = 6.5 Hz, CH ₃ ), 1.22-1.32 (m, 44

15 H, 22 x CH ₂ ), 1.54 (pentet, 4H, J = 6.5 Hz, OCH ₂ CH ₂ ), 2.60 (s, 4H, COCH ₂ ), 3.41 (t, 4H, J = 6.5 Hz, OCH ₂ ), 3.47 (s, 4H, OCH ₂ ),10.6 (bs, 2H, COOH); ¹³ C NMR (CDCI ₃ ) δ 175.6 (COOH), 73.3 (CCH ₂ O), 71.9 (OCH ₂ CH ₂ ), 41.1 (qC), 37.8 (HOOCCH ₂ ), 32.1 (CH ₂ CH ₂ CH ₃ ), 29.86, 29.82, 29.60, 29.52 (tetradecyl CH ₂ ), 26.3 (OCH ₂ CH ₂ CH ₂ ), 22.8 (CH ₃ CH ₂ ), 14.3 (CH ₃ ); HR ESI MS m/z calcd for C ₃₆ H ₆₈ O ₆ (M-H) 583.4943, found

20 583.4978.

Example 15A Λ/,Λ/,Λ/',Λ/ ¹ -tetramethyl-3,3-bis(octyloxymethyl)pentanediamide (15a)

[00190] 1-Hydroxybenzotriazole (HOBT, 1.03 g, 7.69 mmol) and 25 Λ/-(3-dimethylaminopropyl)-Λ/'-ethylcarbodiimide hydrochloride (EDCHCI, 1.54 g, 8.07 mmol) are added to a stirred solution of diacid 14a (Example 14A) (1.6 g, 3.9 mmol) and the reaction mixture is stirred for 1 h. Dimethylamine hydrochloride (1.25 g, 15.4 mmol) and triethylamine (2.7 g, 27 mmol) are added and the reaction mixture is stirred for another 24 h, then diluted with dichloromethane (50 ml_). This mixture is washed with 5 water (2 x 30 m!_), brine (20 ml_), dried (Na ₂ SO ₄ ) and concentrated. The residue is purified by flash column chromatography using a gradient of 15 to 30% EtOAc in hexanes as eluent, giving compound 15a as a viscous liquid: yield 1.63 g (91%); R _F 0.5 (ethyl acetate: hexanes 2:1); ¹ H NMR (CDCI ₃ ) δ 0.88 (t, 6H, J = 6.5 Hz, CH ₃ ), 1.26-1.30 (m, 20 H, 10 x CH ₂ ), 1.51 (pentet, 4H, J = 6.5 Hz, OCH ₂ CH ₂ ), 2.65 (s, 4H, COCH ₂ ), 2.89 10 (s, 6H, NCH ₃ ), 3.03 (s, 6H, NCH ₃ ), 3.36 (t, 4H, J = 6.5 Hz, OCH ₂ ), 3.53 (s, 4H, OCH ₂ ); 1 ³ C NMR (CDCI ₃ ) δ 172.4 (CO), 72.7 (CCH ₂ O), 71.4 (OCH ₂ CH ₂ ), 42.1 (qC), 37.9 (NCH ₃ ), 35.5 (NCH ₃ ), 33.6 (NCOCH ₂ ), 32.0 (CH ₂ CH ₂ CH ₂ ), 29.87, 29.63, 29.51 (2 x 3 octyl CH ₂ ), 26.4 (OCH ₂ CH ₂ CH ₂ ), 22.8 (CH ₃ CH ₂ ), 14.2 (CH ₃ ); HR ESI MS m/z calcd for C ₂₇ H ₅₄ N ₂ O ₄ Na (M+Na) 493.3976, found 493.3966.

15 Example 15B

3,3-Bis(decyloxymethyl)-W,/V,/V,/V-tetramethylpentanediam ide (15b)

[00191] 1-Hydroxybenzotriazole (HOBT, 1.14 g, 8.45 mmol), EDCHCI (1.61 g, 8.45 mmol), diacid 14b (Example 14B) (1.9 g, 4.0 mmol), dimethylamine hydrochloride (1.31

20 g, 16.1 mmol) and triethylamine (3.26 g, 32.2 mmol) are reacted following the procedure of Example 15A, giving compound 15b as a viscous liquid: yield 2.0 g (95%); R _F 0.5 (ethyl acetate: hexanes 2:1); ¹ H NMR (CDCI ₃ ) δ 0.89 (t, 6H, J = 6.5 Hz, CH ₃ ), 1.26-1.35 (m, 28 H, 14 x CH ₂ ), 1.53 (pentet, 4H, J = 6.5 Hz, OCH ₂ CH ₂ ), 2.67 (s, 4H, COCH ₂ ), 2.91 (s, 6H, NCH ₃ ), 3.04 (s, 6H, NCH ₃ ), 3.38 (t, 4H, J = 6.5 Hz, OCH ₂ ), 3.54 (s, 4H, OCH ₂ );

25 ¹³ C NMR (CDCI ₃ ) δ 172.4 (CO), 72.7 (CCH ₂ O), 71.4 (OCH ₂ CH ₂ ), 42.1 (qC), 38.0 (NCH ₃ ), 35.5 (NCH ₃ ), 33.6 (NCOCH ₂ ), 32.1 (CH ₃ CH ₂ CH ₂ ), 2 x 29.87, 29.78, 29.69, 29.52 (2 x 4 decyl CH ₂ ), 26.4 (OCH ₂ CH ₂ CH ₂ ), 22.8 (CH ₃ CH ₂ ), 14.3 (CH ₃ ); HR ESI MS m/z calcd for C ₃₁ H ₆₂ N ₂ O ₄ Na (M+Na) 549.4602, found 549.4580. Example 15C 3,3-Bis(dodecyloxymethyl)-Λ/,Λ/,Λr,Λr-tetramethylpentane diamide (15c)

1CH ₃

[00192] 1-Hydroxybenzotriazole (HOBT, 0.96 g, 7.2 mmol), EDCHCI (1.36 g, 7.15 mmol), diacid 14b (Example 14C) (1.8 g, 3.4 mmol), dimethylamine hydrochloride (1.11 g, 13.6 mmol) and triethylamine (2.06 g, 20.5 mmol) are reacted following the procedure of Example 15A to give the title compound (15c) as a viscous liquid: yield 1.7 g (86%); R _F 0.5 (ethyl acetate: hexanes 2:1); ¹ H NMR (CDCI ₃ ) δ 0.89 (t, 6H, J = 6.5 Hz, CH ₃ ), 1.22-1.34 (m, 36 H, 18 x CH ₂ ), 1.50 (pentet, 4H, J = 6.5 Hz, OCH ₂ CH ₂ ), 2.65 (s, 4H, COCH ₂ ), 2.89 (s, 6H, NCH ₃ ), 3.03 (s, 6H, NCH ₃ ), 3.36 (t, 4H, J = 6.5 Hz, OCH ₂ ), 3.52 (s, 4H, OCH ₂ ); ¹³ C NMR (CDCI ₃ ) δ 172.4 (CO), 72.7 (CCH ₂ O), 71.4 (OCH ₂ CH ₂ ), 42.1 (qC), 37.9 (NCH ₃ ), 35.5 (NCH ₃ ), 33.5 (NCOCH ₂ ), 32.1 (CH ₃ CH ₂ CH ₂ ), 29.88 (x3), 29.83 (x2), 29.70, 29.52 (7 dodecyl CH ₂ ), 26.4 (OCH ₂ CH ₂ CH ₂ ), 22.8 (CH ₃ CH ₂ ), 14.2 (CH ₃ ); HR ESI MS m/z calcd for C ₃₅ H ₇₀ N ₂ O ₄ Na (M+Na) 605.5228, found 605.5183. Example 15D

Λ/,Λ/,Λ/',Λr-Tetramethyl-3,3-bis(tetradecyloxymethyl) pentanediamide (15d)

H ₃ H ₃

[00193] 1-Hydroxybenzotriazole (HOBT, 2.0 g, 15 mmol), EDCHCI (2.89 g, 15.1 mmol), diacid 14d (Example 14D) (4.2 g, 7.2 mmol), dimethylamine hydrochloride (2.40 g, 29.5 mmol) and triethylamine (5.81 g, 57.5 mmol) are reacted following the procedure of Example 15A to give the title compound (15d) as a solid: yield 4.1 g (89%); mp 52-54°C; R _F 0.46 (ethyl acetate: hexanes 2:1); ¹ H NMR (CDCI ₃ ) δ 0.88 (t, 6H, J = 7.0 Hz, CH ₃ ), 1.26-1.42 (m, 44 H, 22 x CH ₂ ), 1.51 (p, 4H, J = 6.5 Hz, OCH ₂ CH ₂ ), 2.65 (s, 4H, COCH ₂ ), 2.89 (s, 6H, NCH ₃ ), 3.02 (S ₇ 6H ₁ NCH ₃ ), 3.36 (t, 4H, J = 6.5 Hz, OCH ₂ ), 3.52 (s, 4H, OCH ₂ ); ¹³ C NMR (CDCI ₃ ) δ 172.4 (CO), 72.7 (CCH ₂ O) ₁ 71.4 (OCH ₂ CH ₂ ), 42.1 (qC), 37.9 (NCH ₃ ), 35.5 (NCH ₃ ), 33.6 (NCOCH ₂ ), 32.1 (CH ₃ CH ₂ CH ₂ ), 29.9 - 29.8 (7C), 29.69, 29.52 (2 x 9 tetradecyl CH ₂ ), 26.4 (OCH ₂ CH ₂ CH ₂ ), 22.9 (CH ₃ CH ₂ ), 14.3 (CH ₃ ); HR ESI MS m/z calcd for C ₃₉ H ₇₈ N ₂ O ₄ Na (M+Na) 661.5854, found 661.5823.

5 Example 16A

W,W,W,yV-Tetramethyl-3,3-bis(octyloxymethyl)-1,5-pentaned iamine (16a)

16a

[00194] Diamide 15a (Example 15A) (0.9 g, 1.91 mmol) is added dropwise to a stirred suspension of LiAIH ₄ (0.29 g, 7.65 mmol) in THF (50 ml.) at O ⁰ C, then the reaction

10 mixture is stirred at rt for 6 h. Ethyl acetate (50 ml_) is added dropwise, followed by water (0.3 mL), then 1 M NaOH (0.3 ml_). The mixture is filtered on a bed of celite™ that is washed with hot ethyl acetate. The combined filtrate and washings are dried (Na ₂ SO ₄ ), filtered and concentrated to a residue that is purified by flash column chromatography. Elution using a gradient of 5 to 15% MeOH in dichloromethane gives compound 16a as a

15 light brown liquid: yield: 0.67 g (80%); R _F on basic alumina 0.46 (dichloromethane: methanol 96:4); ¹ H NMR (CDCI ₃ ) δ 0.88 (t, 6H, J = 7.0 Hz, CH ₃ ), 1.22-1.38 (m, 20 H, 1Ox CH ₂ ), 1.43-1.54 (m, 8H, NCH ₂ CH ₂ , OCH ₂ CH ₂ ), 2.21 (s, 12H, NCH ₃ ), 2.27 (t, 4H, J = 8.0 Hz, NCH ₂ ), 3.19 (s, 4H, OCH ₂ ), 3.34 (t, 4H, J = 6.5 Hz, OCH ₂ ); ¹³ C NMR (CDCI ₃ ) δ 73.8 (CCH ₂ O), 71.5 (OCH ₂ CH ₂ ), 54.5 (NCH ₂ ), 45.8 (NCH ₃ ), 40.2 (qC), 32.0 (CH ₃ CH ₂ CH ₂ ),

20 30.3 (NCH ₂ CH ₂ ), 29.89, 29.64, 29.50 (2 x 3 octyl CH ₂ ), 26.5 (OCH ₂ CH ₂ CH ₂ ), 22.8 (CH ₃ CH ₂ ), 14.3 (CH ₃ ); HR ESI MS m/z calcd for C ₂₇ H ₅₈ N ₂ O ₂ (M+1) 443.4571 , found 443.4558. Example 16B 3,3-Bis(decyloxymethyl)-/V,A/,/V,/V-tetramethyl-1,5-pentaned iamine (16b)

H

16b

[00195] Reaction of diamide 15b (Example 15B) (1.9 g, 3.6 mmol) with LiAIH ₄ (0.54 g, 5 14 mmol) in THF (50 mL) following the procedure of Example 16A gives compound 16b as light brown liquid: yield: 1.1 g (61%); R _F on basic alumina 0.44 (dichloromethane: methanol 96:4); ¹ H NMR (CDCI ₃ ) δ 0.88 (t, 6H, J = 7.0 Hz, CH ₃ ), 1.22-1.45 (m, 28 H, 14x CH ₂ ), 1.49-1.54 (m, 8H, NCH ₂ CH ₂ , OCH ₂ CH ₂ ), 2.27 (s, 12H, NCH ₃ ), 2.37 (t, 4H, J = 7.5, NCH ₂ ), 3.19 (s, 4H, OCH ₂ ), 3.34 (t, 4H, J = 6.5 Hz, OCH ₂ ); ¹³ C NMR (CDCI ₃ ) δ 73.8 10 (CCH ₂ O), 71.6 (OCH ₂ CH ₂ ), 54.5 (NCH ₂ ), 45.5 (NCH ₃ ), 40.3(qC), 32.1 (CH ₃ CH ₂ CH ₂ ), 30.01 (NCH ₂ CH ₂ ), 29.87, 29.85, 29.79, 29.68, 29.52 (2 x 5 decyl CH ₂ ), 26.5 (OCH ₂ CH ₂ CH ₂ ), 22.9 (CH ₃ CH ₂ ), 14.3 (CH ₃ ); HR ESI MS m/z calcd for C ₂₇ H ₅₈ N ₂ O ₂ (M+1) 443.4571 , found 443.4558.

Example 16C 15 3,3-Bis(dodecyloxymethyl)-Λ/,Λ/,ΛP,ΛT-tetramethyl-1,5-pe ntanediamine (16c)

16c

[00196] Reaction of diamide 15c (Example 15C) (1.9 g, 3.3 mmol) with LiAIH ₄ (0.62 g, 16 mmol) in THF (50 mL) following the procedure of Example 16A gives compound 16c as a light brown liquid: yield 1.3 g (72%); R _F on basic alumina 0.52 (DCM: methanol 20 95:5); ¹ H NMR (CDCI ₃ ) δ 0.88 (t, 6H, J = 7.0 Hz, CH ₃ ), 1.22-1.45 (m, 36 H, 18x CH ₂ ), 1.45-1.54 (m, 8H, NCH ₂ CH ₂ , OCH ₂ CH ₂ ), 2.21 (s, 12H, NCH ₃ ), 2.26-2.29 (m, 4H, J = 8.5 Hz, NCH ₂ ), 3.18 (s, 4H, OCH ₂ ), 3.34 (t, 4H, J = 6.5 Hz, OCH ₂ ); ¹³ C NMR (CDCI ₃ ) δ 73.8 (CCH ₂ O), 71.5 (OCH ₂ CH ₂ ), 54.5 (NCH ₂ ), 45.8 (NCH ₃ ), 40.2 (qC), 32.1 (CH ₂ CH ₂ CH ₂ ), 30.2 (NCH ₂ CH ₂ ), 29.9 -20.8 (4C), 29.69, 29.52 (2 x 7 dodecyl CH ₂ ), 26.5 (OCH ₂ CH ₂ CH ₂ ), 22.8 (CH ₃ CH ₂ ), 14.3 (CH ₃ ); HR ESI MS m/z calcd for C ₃₅ H ₇₄ N ₂ O ₂ (M+ 1) 555.5823, found 555.5854.

Example 16D A/,/V,/V,/V-Tetramethyl-3,3-bis(tetradecyloxymethyl)-1,5-pen tanediamine (16d)

H H ₃ 1 ^6d

[00197] Reaction of diamide 15d (Example 15D) (2.2 g, 3.4 mmol) with LiAIH ₄ (0.65 g, 17 mmol) in THF (50 ml.) following the procedure of Example 16A gives a residue that is purified by flash column chromatography. Elution using a gradient of 10 to 15% MeOH in DCM gives compound 16d as a light brown liquid: yield 1.7 g (81%); R _F on basic alumina 0.55 (DCM: methanol 95:5); ¹ H NMR (CDCI ₃ ) δ 0.88 (t, 6H, J = 7.0 Hz, CH ₃ ), 1.21-1.37 (m, 44 H, 22x CH ₂ ), 1.46-1.54 (m, 8H, NCH ₂ CH ₂ , OCH ₂ CH ₂ ), 2.23 (s, 12H, NCH ₃ ), 2.30- 2.33 (m, 4H, J = 8.0 Hz, NCH ₂ ), 3.18 (s, 4H, OCH ₂ ), 3.34 (t, 4H, J = 6.5 Hz, OCH ₂ ); ¹³ C NMR (CDCI ₃ ) δ 73.7 (CCH ₂ O), 71.5 (OCH ₂ CH ₂ ), 54.4 (NCH ₂ ), 45.5 (NCH ₃ ), 40.2 (qC), 32.1 (CH ₂ CH ₂ CH ₃ ), 30.0 (NCH ₂ CH ₂ ), 29.9-29.8, 29.68, 29.51 (tetradecyl CH ₂ ), 26.9 (OCH ₂ CH ₂ CH ₂ ), 22.8 (CH ₃ CH ₂ ), 14.3 (CH ₃ ); HR ESI MS m/z calcd for C ₃₉ H ₈₂ N ₂ O ₂ (M+1) 611.6449, found 611.6466.

Example 17A

Λ/,Λ/,Λ/,Λr,Λ/',ΛT-hexamethyl-3,3-bis(octyloxymethy l)-1,5φentanediammonium diiodide (17a)

[00198] A solution of methyl iodide (1.6 g, 11 mmol) and diamine 16a (Example 16A) (0.50 g, 1.1 mmol) in THF (20 ml_) is refluxed for 36 h, then concentrated. The solid residue is purified by flash column chromatography using 10% methanol in dichloromethane as eluent to give the title product as an off-white solid: yield 0.70 g (85%); mp 223-225°C; R _F 0.5 on basic alumina (8% methanol in dichloromethane); ¹ H NMR (CDCI ₃ ) δ 0.88 (t, 6H ₁ J = 7.0 Hz, CH ₃ ), 1.22-1.28 (m, 20 H, 10 x CH ₂ ), 1.45 (t, 4H, J = 6.0 Hz, OCH ₂ CH ₂ ), 1.83 (AA ¹ part of AA ¹ XX ¹ pattern, 4H, NCH ₂ CH ₂ ), 3.13 (s, 4H, OCH ₂ ), 3.15 (s, 18H, NCH ₃ ), 3.18 (t, 4H, J= 7.0 Hz, OCH ₂ ), 3.73 (XX part of AA ¹ XX ¹ 5 pattern, 4H, NCH ₂ ); ¹³ C NMR (CDCI ₃ ) δ 71.7 (CCH ₂ O), 71.5 (OCH ₂ CH ₂ ), 62.8

(CH ₂ N(CHa) ₃ ), 54.2 (NCH ₃ ), 41.6 (qC), 32.0 (CH ₂ CH ₂ CH ₂ ), 29.82, 29.58, 29.50 (3 octyl CH ₂ ), 26.6 (OCH ₂ CH ₂ CH ₂ ), 24.6 (NCH ₂ CH ₂ ), 22.8 (CH ₃ CH ₂ ), 14.3 (CH ₃ ); HR ESI MS m/z calcd for C ₂₉ H ₆₄ IN ₂ O ₂ (M-I) 599.4007, found 599.3993.

Example 17B

10 3,3-Bis(decyloxymethyl)-tø,W,W,Λf ,W',ΛT-hexamethyl-1 ,5-pentanediammonium diiodide (17b)

[00199] Reaction of methyl iodide (1.93 g, 13.7 mmol) and diamine 16b (Example 16B) (0.68 g, 1.4 mmol) in THF following the procedure of Example 17A gives the title product

15 as an off-white solid: yield 0.80 g (80%); mp 214-216°C; R _F 0.5 on basic alumina (7% methanol in dichloromethane); ¹ H NMR (CDCI3) δ 0.88 (t, 6H, J = 7.0 Hz, CH ₃ ), 1.24- 1.35 (m, 28 H, 14 x CH ₂ ), 1.52 (t, 4H, J = 6.5 Hz, OCH ₂ CH ₂ ), 1.93 (AA ¹ part of AA ¹ XX ¹ pattern, 4H, NCH ₂ CH ₂ ), 3.39 (s, 4H, OCH ₂ ), 3.42 (s, 18H, NCH ₃ ), 3.44 (t, 4H, J= 7.0 Hz, OCH ₂ ), 4.02 (XX part of AA ¹ XX ¹ pattern, 4H, NCH ₂ ); ¹³ C NMR (CDCI ₃ ) δ 71.7 (CCH ₂ O),

20 71.5 (OCH ₂ CH ₂ ), 62.8 (CH ₂ N(CH ₃ ) ₃ ), 54.2 (NCH ₃ ), 41.5 (qC), 32.1 (CH ₂ CH ₂ CH ₂ ), 29.85, 29.81 , 29.77, 29.62, 29.47 (5 decyl CH ₂ ), 26.5 (OCH ₂ CH ₂ CH ₂ ), 24.6 (NCH ₂ CH ₂ ), 22.9 (CH ₃ CH ₂ ), 14.4 (CH ₃ ); HR ESI MS m/z calcd for C ₃₃ H ₇₂ IN ₂ O ₂ (M-I) 655.4633, found 655.4614. Example 17C

3,3-Bis(dodecyloxymethyl)-Λ/,Λ/,Λ/,Λ/ ¹ ,Λ/',Λ/'-hexamethyl-1,5-pentanediammonium diiodide (17c)

17c

5 [00200] Reaction of methyl iodide (2.56 g, 18.0 mmol) with diamine 16c (Example 16C) (1.00 g, 1.80 mmol) following the procedure of Example 17A gives the title product as an off-white solid: yield 1.20 g (78%); mp 220-223 ⁰ C; R _F 0.5 on basic alumina (7% methanol in dichloromethane); ¹ H NMR (CDCI ₃ ) δ 0.88 (t, 6H, J = 7 .0 Hz, CH ₃ ), 1.23-1.36 (m, 36 H, 18 x CH ₂ ), 1.52 (t, 4H, J = 6.5 Hz, OCH ₂ CH ₂ ), 1.89 (AA' part of AA ¹ XX ¹ pattern, 4H,

10 NCH ₂ CH ₂ ), 3.38 (s, 4H, OCH ₂ ), 3.44 (t, 4H, J = 7.0 Hz, OCH ₂ ), 3.45 (s, 18H, NCH ₃ ), 3.94 (XX ¹ part Of AA ¹ XX ¹ pattern, 4H, NCH ₂ ); ¹³ C NMR (CDCI ₃ ) 71.7 (CCH ₂ O), 71.5 (OCH ₂ CH ₂ ), 62.8 (CH ₂ N(CHa) ₃ ), 54.2 (NCH ₃ ), 41.5 (qC), 32.1 (CH ₂ CH ₂ CH ₂ ), 29.90 - 29.75 (5C), 29.62, 29.47 (7 dodecyl CH ₂ ), 26.5 (OCH ₂ CH ₂ CH ₂ ), 24.6 (NCH ₂ CH ₂ ), 22.9 (CH ₃ CH ₂ ), 14.3 (CH ₃ ); HR ESI MS m/z calcd for C ₃₇ H ₈₀ IN ₂ O ₂ (M-I) 711.5259, found

15 711.5239.

Example 17D

Λ/,Λ/,Λ/,Λ/',Λ/',Λr-Hexamethyl-3,3-bis(tetradecylox ymethyl)-1,5-pentanediammonium diiodide (17d)

20 [00201] Reaction of methyl iodide (2.32 g, 16.4 mmol) and diamine 16d (Example 16D) (1.0 g, 1.6 mmol) following the procedure of Example 17A (without chromatography) gives a solid residue that is crystallized from dichloromethane and dried under vacuum to give compound 17d as an off-white shiny solid: yield 1.2 g (82%); mp 218-221 ⁰ C; R _F 0.6 on basic alumina (7% methanol in dichloromethane); ¹ H NMR (CDCI ₃ ) δ 0.88 (t, 6H, J =

25 7.0 Hz, CH ₃ ), 1.27 (m, 44 H, 22x CH ₂ ), 1.52 (t, 4H, J = 6.5 Hz, OCH ₂ CH ₂ ), 1.93 (AA ¹ part of AA ¹ XX ¹ pattern, 4H, NCH ₂ CH ₂ ), 3.39 (s, 4H, OCH ₂ ), 3.43 (s, 18H, NCH ₃ ), 3.44 (t, 4H, J = 7.0Hz, OCH ₂ ), 4.03 (XX ¹ part of AA ¹ XX ¹ pattern, 4H, NCH ₂ ); ¹³ C NMR (CDCI ₃ ) δ 71.7 (CCH ₂ O), 71.5 (OCH ₂ ), 62.8 (CH ₂ N(CH ₃ ) ₃ ), 54.1 (NCH ₃ ), 41.4 (qC), 32.1 (CH ₂ CH ₂ CH ₂ ), 29.90 - 29.75 (7C), 29.64, 29.50 (tetradecyl CH ₂ ), 26.5 (OCH ₂ CH ₂ CH ₂ ), 24.6 (NCH ₂ CH ₂ ), 22.8 (CH ₃ CH ₂ ), 14.2 (CH ₃ ); HR ESI MS m/z calcd for C ₄ iH ₈₈ IN ₂ O ₂ (M-1) 767.5885, found 767.5907.

Example 18A Λ/,Λ/,Λ/',Λ/'-tetramethyl-4,4-bis(octyloxymethyl)-2,5-he ptadienediamide (18a)

[00202] A solution of dry dimethyl sulfoxide (DMSO) (0.47 g, 6.11 mmol) in dichloromethane (2 ml.) is added dropwise to a stirred solution of oxalyl chloride (0.38 g, 3.0 mmol) in dichloromethane (5 ml.) at -78 ⁰ C. After the reaction mixture had been stirred for 30 min, a solution of diol 2a (Example 2A) (0.50 g, 1.4 mmol) is added and the reaction mixture is stirred for 1.5 h at -78°C, then Et ₃ N (0.98 g, 9.7 mmol) is added slowly. The reaction mixture is stirred for 30 min, allowed to warm to rt, the quenched by addition of a saturated NH ₄ CI solution (10 ml_). The reaction mixture is extracted with dichloromethane (3 x 50 ml_), and the combined organic layers are washed with 2M HCI (5 ml_), water (2 x 5ml_), brine (5 ml_), then dried (Na ₂ SO ₄ ) and concentrated to give 2,2- bis(octyloxymethyl)propanedial as a colorless viscous oil: yield 0.47 g, 95%; R _F 0.56 (hexanes: ethyl acetate 8:2); ¹ H NMR δ 0.88 (t, 6H, J = 7.0 Hz, 2 x Me), 1.26-1.32 (br s, 2OH, 10 x CH ₂ ), 1.51 (p, 4H, J = 7.2 Hz, 2 OCH ₂ CH ₂ ), 3.42 (t, 4H, J = 6.5 Hz, decyl OCH ₂ ), 3.87 (s, 4H, OCH ₂ C), 9.74 (s, 2H ₁ CHO); ¹³ C NMR δ 199.4 (CHO), 72.3 (CH ₂ CH ₂ OC), 68.6 (OCH ₂ C), 43.8 (q C), 31.7 (CH ₂ CH ₂ CH ₃ ), 29.76, 29.62, 29.48, 29.44, 29.37 (5 decyl CH ₂ ), 26.12 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.2 (Me); LR ESI m/z calcd for C ₂₁ H ₄₀ O ₄ Na. MeOH 411.31 , found 411.3; for C ₂₁ H ₄₀ O ₄ Na.2MeOH 443.33, found 443.3; for 2 C ₂₁ H ₄₀ O ₄ +Na+H ₂ O 753.54, found 753.6.

[00203] Diethyl Λ/,Λ/-dimethylcarbamoylmethylphosphonate (prepared by the method of Paul A. Bartlett, Nicholas I. Carruthers, Beat M. Winter, and Karen P. Long. J.Org.Chem. 47, 1284-1291 , 1982) (4.1 g, 18 mmol) in THF (10 mL) is added in portions to a stirred suspension of NaH (0.45 g, 18 mmol) in THF (80 mL) at rt and the reaction mixture is stirred for 2 h, then cooled to 0 ⁰ C. A solution of 2,2-bis(octyloxymethyl)propanedial (1.6 g, 4.5 mmol) in THF (10 ml_) is added and the reaction mixture is stirred for 24 h at rt. A saturated aqueous ammonium chloride solution (20 mL) is added to the reaction mixture and then the volatile organic components are removed by concentration. The resulting solution is extracted with ethyl acetate (3 x 30 mL). The combined organic layers are washed with water (2 x 20 mL), brine (20 mL), dried (Na ₂ SO ₄ ), filtered and concentrated. The residue is purified by flash column chromatography using a gradient of 80 to 90% EtOAc in hexanes as eluent, yielding compound 18a as a viscous liquid: yield 1.4g (63%); R _F 0.35 (dichloromethane: methanol 94:6); ¹ H NMR δ 0.88 (t, 6H, J = 7 Hz, 2 x Me), 1.26-1.34 (br s, 2OH, 1O x CH ₂ ), 1.53 (pentet, 4H, J = 7 Hz, 2 OCH ₂ CH ₂ ), 2.99 (s, 3H, NCH ₃ ), 3.05 (s, 3H, NCH ₃ ), 3.39 (t, 4H, J = 6.5 Hz, decyl OCH ₂ ), 3.49 (s, 4H, OCH ₂ C), 6.36 (d, 2H, J = 16 Hz, COCHCH), 6.86 (d, 2H, J = 16 Hz, COCHCH); ¹³ C NMR δ 166.8 (C=O), 145.3 (CH=CHC), 121.9 (COCH=), 72.9 (CH ₂ CH ₂ OC), 71.9 (OCH ₂ C), 48.9 (q C), 37.5 (NCH ₃ ), 35.8 (NCH ₃ ), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.77, 29.61 , 29.45 (3 octyl CH ₂ ), 26.4 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.2 (Me); HR ESI MS m/z calcd for C ₂₉ H ₅₄ N ₂ O ₄ Na (M+Na) 517.3976, found 517.3971.

Example 18B 4,4-Bis(decyloxymethyl)-Λ/,Λ/,Λ/',Λ/ ^I -tetramethyl-2,5-heptadienediamide (18b)

[00204] Treatment of diol 2b (Example 2B) (2.3 g, 5.5 mmol) in dry dichloromethane with the Swern oxidation mixture [DMSO (1.89 g, 24.3 mmol), oxalyl chloride (1.54 g, 12.2 mmol)] followed by workup, following the procedure of Example 18A, gives 2,2- bis(decyloxymethyl)propanedial as a light yellow oil: yield 2.1 g, 92 %; R _F 0.7 (hexanes: ethyl acetate 8:2); ¹ H NMR δ 0.88 (t, 6H, J = 6.5 Hz, 2 x Me), 1.25-1.31 (brs, 28H, 14 x CH ₂ ), 1.51 (pentet, 4H, J = 7.2 Hz, 2 OCH ₂ CH ₂ ), 3.41 (t, 4H, J = 6.5 Hz, decyl OCH ₂ ), 3.87 (s, 4H, OCH ₂ C), 9.74(s, 2H ₁ CHO); ¹³ C NMR δ 199.5 (CHO), 72.3 (CH ₂ CH ₂ OC), 68.6 (OCH ₂ C), 43.7 (q C), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.72, 29.53, 29.46 ( decyl CH ₂ ), 26.13 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.3 (Me); LR ESI MS m/z calcd for C ₂₅ H ₄₈ O ₄ Na-MeOH 467.37, found 467.4. [00205] A mixture of diethyl Λ/,Λ/-dimethylcarbamoylmethylphosphonate (4.54 g, 20.4 mmol), NaH (0.49 g, 20.6 mmol) and 2,2-bis(decyloxymethyl)propanedial (2.0 g, 4.8 mmol) in THF (100 ml.) is treated following the procedure of Example 18A to give compound 18b as a colorless liquid: yield, 1.7 g (64%); R _F 0.39 (dichloromethane: methanol 95:5); ¹ H NMR δ 0.88 (t, 6H, J = 7 Hz, 2 x Me), 1.26-1.31 (br s, 28H, 14 x CH ₂ ), 5 1.52 (pentet, 4H, J = 7 Hz, 2 OCH ₂ CH ₂ ), 2.99 (s, 3H, NCH ₃ ), 3.02 (s, 3H, NCH ₃ ), 3.39 (t, 4H, J = 6.5 Hz, decyl OCH ₂ ), 3.49 (s, 4H, OCH ₂ C), 6.36 (d, 2H, J = 15.5 Hz, COCH=), 6.86 (d, 2H, J = 15.5 Hz, =CHC); ¹³ C NMR δ 166.8 (C=O), 145.3 (CH=CHC), 121.9 (COCH=), 72.9 (CH ₂ CH ₂ OC), 71.9 (OCH ₂ C), 48.9 (q C), 37.5 (NCH ₃ ), 35.8 (NCH ₃ ), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.79, 29.76, 29.66, 29.49 (5 decyl CH ₂ ), 26.4 (CH ₂ CH ₂ CH ₂ O), 22.8 10 (CH ₂ CH ₃ ), 14.2 (Me); HR ESI MS m/z calcd for C ₃₃ H ₆₂ N ₂ O ₄ Na (M+Na) 573.4602, found 573.4592.

Example 18C 4,4-Bis(dodecyloxymethyl)-Λ/,Λ/,yV,Λr-tetramethyl-2,5-hep tadienediamide (18c)

1CH ₃

15 [00206] Treatment of diol 2c (Example 2C) (1.3 g, 2.8 mmol) in dry dichloromethane (30 ml.) with the Swern oxidation mixture [DMSO (1.74 g, 22.3 mmol), oxalyl chloride (1.42 g, 11.2 mmol)] following the procedure of Example 18A gives 2,2- bis(dodecyloxymethyl)propanedial as a light yellow oil: yield 1.2 g, 92 %; R _F 0.7 (hexanes: ethyl acetate 8:2); ¹ H NMR δ 0.88 (t, 6H, J = 7 Hz, 2 x Me), 1.25-1.32 (br s,

20 36H, 18 x CH ₂ ), 1.52 (pentet, 4H, J = 7.2 Hz, 2 OCH ₂ CH ₂ ), 3.41 (t, 4H, J = 6.5 Hz, decyl OCH ₂ ), 3.87 (s, 4H, OCH ₂ C), 9.74 (s, 2H ₁ CHO); ¹³ C NMR δ 199.4 (CHO), 72.3 (CH ₂ CH ₂ OC), 68.6 (OCH ₂ C), 43.7 (q C), 32.1 (CH ₂ CH ₂ CH ₃ ), 29.81 , 29.78, 29.72, 29.53, 29.44, (decyl CH ₂ ), 26.1 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.2 (Me).

[00207] A mixture of diethyl Λ/,Λ/-dimethylcarbamoylmethylphosphonate (2.67 g, 11.9 25 mmol), NaH (0.29 g,12 mmol) and 2,2-bis(dodecyloxymethyl)propanedial (1.1 g, 2.3 mmol) in THF(IOO ml.) is treated following the procedure of Example 18A to give compound 18c as a colorless solid: yield 1.25 g (69%); mp 52-54°C; R _F 0.42 (dichloromethane: methanol 95:5); ¹ H NMR δ 0.88 (t, 6H, J = 7 Hz, 2 x Me), 1.26-1.32 (br s, 36H, 18 x CH ₂ ), 1.52 (pentet, 4H, J = 7 Hz ₁ 2 OCH ₂ CH ₂ ), 2.99 (S ₁ 3H, NCH ₃ ), 3.05 (s, 3H, NCH ₃ ), 3.39 (t, 4H, J = 6.5 Hz, decyl OCH ₂ ), 3.49 (s, 4H, OCH ₂ C), 6.36 (d, 2H, J = 15.5 Hz, COCH=), 6.86 (d, 2H, J = 15.5 Hz, =CHC); ¹³ C NMR δ 166.8 (C=O), 145.3 (CH=CHC), 121.9 (COCH=), 72.9 (CH ₂ CH ₂ OC), 71.9 (OCH ₂ C), 48.9 (qC), 37.5 (NCH ₃ ), 35.8 (NCH ₃ ), 32.1 (CH ₂ CH ₂ CH ₃ ), 29.86, 29.82, 29.68, 29.52 (5 dodecyl CH ₂ ), 26.4 5 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.3 (Me); HR ESI MS m/z calcd for C ₃₇ H ₇₀ N ₂ O ₄ Na (M+Na) 629.5228, found 629.5244.

Example 18D A/,Λ/,Λ/',Λ/'-Tetramethyl-4,4-bis(tetradecyloxymethyl)-2, 5-heptadienediamide (18d)

10 [00208] Treatment of diol 2d (Example 2D) (3.0 g, 5.7 mmol) in dry DCM (30 ml.) with the Swern oxidation mixture [DMSO (2.03 g, 26.1 mmol), oxalyl chloride (1.65 g, 13.0 mmol)] following the procedure of Example 18A gives

2,2-bis(tetradecyloxymethyl)propanedial as a light yellow oil: yield 2.5 g, 86 %; R _F 0.7 (hexanes: ethyl acetate 8:2); ¹ H NMR δ O. 0.88 (t, 6H, J = 7 Hz, 2 x Me), 1.25-1.32 (br s,

15 36H, 18 x CH ₂ ), 1.51 (pentet, 4H, J = 7.2 Hz, 2 OCH ₂ CH ₂ ), 3.40 (t, 4H, J = 6.5 Hz, decyl OCH ₂ ), 3.87 (S, 4H, OCH ₂ C), 9.74 (s, 2H ₁ CHO); ¹³ C NMR δ 199.5 (CHO), 72.4 (CH ₂ CH ₂ OC), 68.6 (OCH ₂ C), 43.7 (q C), 32.1 (CH ₂ CH ₂ CH ₃ ), 29.81 , 29.77, 29.52, 29.45 (decyl CH ₂ ), 26.1 (CH ₂ CH ₂ CH ₂ O), 22.9 (CH ₂ CH ₃ ), 14.2 (Me); LR ESI MS m/z calcd for C ₃₃ H ₆₄ O ₄ Na-MeOH, 579.50, found 579.5.

20 [00209] A mixture of diethyl Λ/,Λ/-dimethylcarbamoylmethylphosphonate (4.68 g, 20.9 mmol), NaH (0.51 g, 21 mmol) and 2,2-bis(tetradecyloxymethyl)propanedial (2.5 g, 4.7 mmol) in THF (100 mL) is treated following the procedure of Example 18A to give compound 18d as a colorless solid: yield 2.0 g (64%); mp 59-61 ⁰ C; R _F 0.43 (dichloromethane: methanol 95:5); ¹ H NMR δ 0.88 (t, 6H, J = 7 Hz, 2 x Me), 1.26-1.32 (br

25 s, 44H, 22 x CH ₂ ), 1.53 (pentet, 4H, J = 7 Hz, 2 OCH ₂ CH ₂ ), 2.99 (s, 3H, NCH ₃ ), 3.05 (s, 3H, NCH ₃ ), 3.39 (t, 4H, J = 6.5 Hz, decyl OCH ₂ ), 3.50 (s, 4H, OCH ₂ C), 6.37 (d, 2H, J = 15.5 Hz, COCH=), 6.86 (d, 2H, J = 15.5 Hz, =CHC); ¹³ C NMR δ 166.8 (C=O), 145.3 (CH=CHC), 121.9 (COCH=), 72.9 (CH ₂ CH ₂ OC), 71.9 (OCH ₂ C), 48.9 (q C), 37.5 (NCH ₃ ), 35.8 (NCH ₃ ), 32.1 (CH ₂ CH ₂ CH ₃ ), 29.86, 29.82, 29.77, 29.68, 29.52 (5 tetradecyl CH ₂ ), 26.4 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.3 (Me); HR ESI MS m/z calcd f OrC ₄₁ H ₇₈ N ₂ O ₄ Na (M+Na) 685.5854, found 685.5814.

Example 19A Λ/,Λ/,Λ/',Λ/'-Tetramethyl-4,4-bis(octyloxymethyl)heptane diamide (19a)

1 ^9a

[00210] A mixture of compound 18a (Example 18A) (0.5 g, 1.0 mmol) and 10% Pd/C wet Degussa type catalyst (50 mg) in ethyl acetate (50 mL) is stirred under H ₂ at atmospheric pressure for 24 h. The reaction mixture is filtered using a celite™ bed and the filtrate is concentrated to give compound 19a as a colorless liquid: yield 0.46 g (91%); R _F 0.5 (dichloromethane: methanol 95:5); ¹ H NMR δ 0.88 (t, 6H, J = 6.5 Hz, 2 x Me), 1.25-1.31 (br s, 2OH, 1O x CH ₂ ), 1.50 (pentet, 4H, J = 7 Hz, 2 OCH ₂ CH ₂ ), 1.61 (4H, AA'XX' pattern, CCH ₂ ), 2.32 (4H, AA'XX' pattern, COCH ₂ ), 2.99 (s, 3H ₁ NCH ₃ ), 3.07 (s, 3H, NCH ₃ ), 3.22 (s, 4H, OCH ₂ C), 3.34 (t, 4H, J = 6.5 Hz, decyl OCH ₂ ); ¹³ C NMR δ 173.8 (C=O), 73.9 (CH ₂ CH ₂ OC), 71.7 (OCH ₂ C), 40.6 (qC), 37.4 (NCH ₃ ), 35.6 (NCH ₃ ), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.90, 29.64, 29.48 (3 octyl CH ₂ ), 28.04, 27.94 (COCH ₂ CH ₂ , COCH ₂ ), 26.5 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.3 (Me); HR ESI MS m/z calcd for C ₂₉ H ₅₈ N ₂ O ₄ Na (M+Na) 521.4289, found 521.4278.

Example 19B 4,4-Bis(decyloxymethyl)-Λ/,Λ/,/V,/V-tetramethyl-2,5-heptan ediamide (19b)

[00211] Hydrogenation of compound 18b (Example 18B) (1.0 g, 1.8 mmol) following the procedure of Example 19A gives the title compound as a colorless liquid: yield 0.90 g (89%); R _F 0.39 (dichloromethane: methanol 95:5); ¹ H NMR δ 0.88 (t, 6H, J = 7 Hz, 2 x

Me), 1.25-1.31 (br s, 28H, 14 x CH ₂ ), 1.51 (pentet, 4H, J = 7 Hz, 2 OCH ₂ CH ₂ ), 1.61 (4H, AA ¹ XX' pattern, CCH ₂ ), 2.32 (4H, AA'XX' pattern, COCH ₂ ), 2.92 (s, 3H, NCH ₃ ), 3.00 (s, 3H, NCH ₃ ), 3.22 (s, 4H ₁ OCH ₂ C), 3.34 (t, 4H, J = 6.5 Hz, decyl OCH ₂ ); ¹³ C NMR δ 173.8 (C=O), 73.9 (CH ₂ CH ₂ OC), 71.7 (OCH ₂ C), 40.6 (q C), 37.4 (NCH ₃ ), 35.6 (NCH ₃ ), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.90, 29.82, 29.77, 29.67, 29.51 (5 decyl CH ₂ ), 28.04, 27.94 (COCH ₂ CH ₂ , COCH ₂ ), 26.5 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.3 (Me); HR ESI MS m/z calcd for C ₃₃ H ₆₆ N ₂ O ₄ Na 577.4915, found 577.4918.

Example 19C 4,4-Bis(dodecyloxymethyl)-Λ/,Λ/,Λ/',Λ/'-tetramethyl-2,5- heptanediamide (19c)

[00212] Hydrogenation of compound 18c (Example 18C) (0.70 g, 1.2 mmol) following the procedure of Example 19A gives compound 19c as a colorless solid: yield 0.65 g (92%); mp 46-48°C; R _F 0.42 (dichloromethane: methanol 95:5); ¹ H NMR δ 0.88 (t, 6H, J = 7 Hz, 2 x Me), 1.25-1.32 (br s, 36H, 18 x CH ₂ ), 1.52 (pentet, 4H, J = 7 Hz, 2 OCH ₂ CH ₂ ), 1.62 (4H, AA'XX' pattern, CCH ₂ ), 2.33 (4H, AA'XX' pattern, COCH ₂ ), 2.92 (s, 3H, NCH ₃ ), 3.00 (s, 3H, NCH ₃ ), 3.22 (s, 4H, OCH ₂ C), 3.34 (t, 4H, J = 6.5 Hz, decyl OCH ₂ ); ¹³ C NMR δ 173.8 (C=O), 73.9 (CH ₂ CH ₂ OC), 71.7 (OCH ₂ C), 40.6 (q C), 37.4 (NCH ₃ ), 35.5 (NCH ₃ ), 32.1 (CH ₂ CH ₂ CH ₃ ), 29.90, 29.83, 29.70, 29.52 (7 dodecyl CH ₂ ), 28.05, 27.94 (COCH ₂ CH ₂ , COCH ₂ ), 26.5 (CH ₂ CH ₂ CH ₂ O), 22.8 (CH ₂ CH ₃ ), 14.3 (Me); HR ESI MS m/z calcd for C ₃₇ H ₇₄ N ₂ O ₄ Na (M+Na) 633.5541 , found 633.5562. Example 19D

Λ/,Λ/,Λ/',Λ/'-Tetramethyl-4,4-bis(tetradecyloxymethyl )heptanediamide (19d)

[00213] Hydrogenation of compound 18d (Example 18D) (1.60 g, 2.4 mmol) following the procedure of Example 19A gives the title compound as a colorless solid: yield, 1.50 g (94%); mp 47-49°C; R _F 0.43 (dichloromethane: methanol 95:5); ¹ H NMR δ 0.88 (t, 6H, J = 7 Hz, 2 x Me), 1.25-1.32 (br s, 36H, 18 x CH ₂ ), 1.50 (pentet, 4H, J = 7 Hz, 2 OCH ₂ CH ₂ ), 1.62 (4H, AA'XX' pattern, CCH ₂ ), 2.33 (4H, AA ¹ XX' pattern, COCH ₂ ), 2.92 (s, 3H, NCH ₃ ), 3.00 (s, 3H, NCH ₃ ), 3.22 (s, 4H, OCH ₂ C), 3.33 (t, 4H, J = 6.5 Hz, decyl 5 OCH ₂ ); ¹³ C NMR δ 173.8 (C=O), 74.0 (CH ₂ CH ₂ OC), 71.7 (OCH ₂ C), 40.6 (q C), 37.4 (NCH ₃ ), 35.5 (NCH ₃ ), 32.1 (CH ₂ CH ₂ CH ₃ ), 29.87, 29.84, 29.70, 29.53 (9 tetradecyl CH ₂ ), 28.04, 27.94 (COCH ₂ CH ₂ , COCH ₂ ), 26.5 (CH ₂ CH ₂ CH ₂ O), 22.9 (CH ₂ CH ₃ ), 14.4 (Me); HR ESI MS m/z calcd for C ₄ iH ₈₂ N ₂ O ₄ Na (M+Na) 689.6167, found 689.6152.

Example 2OA 10 /V,/V,Λf ,W-Tetramethyl-4,4-bis(octyloxymethyl)-1 ,7-heptanediamine (20a)

20a

[00214] Diamide 19a (Example 19A) (0.6 g, 1.2 mmol) is added dropwise to a stirred suspension of LiAIH ₄ (0.18 g, 4.8 mmol) in THF at O ⁰ C. The reaction mixture is stirred at rt for 6 h, then the excess of LiAIH ₄ is decomposed by dropwise addition of ethyl acetate

15 (50 ml_), water (0.3 mL), then 1M NaOH (0.3 mL) at 10 ⁰ C. The mixture is filtered on a bed of celite™, which is then washed with hot ethyl acetate. The combined filtrate and washings are dried (Na ₂ SO ₄ ), then concentrated to a residue that is purified by flash column chromatography. Elution using a gradient of 5 to 15% MeOH in dichloromethane gives the title compound as a light brown liquid: yield 0.45 g (80%); R _F on basic alumina

20 0.71 (dichloromethane: methanol 94:6); ¹ H NMR (CDCI ₃ ) δ 0.88 (t, 6H, J = 7.0 Hz, CH ₃ ), 1.21-1.33 (m, 24 H, 10 octyl CH ₂ , 2 CCH ₂ ), 1.37-1.43 (m, 4H, NCH ₂ CH ₂ ), 1.51 (pentet, 4H, J = 7 Hz, OCH ₂ CH ₂ ), 2.201 (t, 4H, J = 7.5 Hz, NCH ₂ ), 2.206 (s, 12H, NCH ₃ ), 3.17 (s, 4H, OCH ₂ ), 3.33 (t, 4H, J = 6.5 Hz, OCH ₂ ); ¹³ C NMR (CDCI ₃ ) δ 73.5 (CCH ₂ O), 71.5 (OCH ₂ ), 60.9 (NCH ₂ ), 45.7 (NCH ₃ ), 41.0 (qC), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.85, 29.76, 29.65,

25 29.50 (3 octyl CH ₂ , CCH ₂ ), 26.5 (OCH ₂ CH ₂ CH ₂ ), 22.8 (CH ₂ CH ₃ ), 21.45 (NCH ₂ CH ₂ ), 14.3 (Me); HR ESI MS m/z calcd for C ₂₉ H ₆₃ N ₂ O ₂ (M+H) 471.4884, found 471.4885. Example 2OB 4,4-Bis(decyloxymethyl)-W,/\/,/V,W-tetramethyl-1,7-heptanedi amine (20b)

[00215] Diamide 19b (Example 19B) (0.90 g, 1.6 mmol) is reacted with LiAIH ₄ (0.3 g, 8 5 mmol) following the procedure of Example 2OA to give the title compound as a light brown liquid: yield 0.60 g (70%); R _F on basic alumina 0.52 (DCM: methanol 95:5); ¹ H NMR (CDCI ₃ ) δ 0.88 (t, 6H, J = 7.0 Hz ₁ CH ₃ ), 1.21-1.33 (m, 32 H, 14 decyl CH ₂ , 2 CCH ₂ ), 1.39-1.44 (m, 4H, NCH ₂ CH ₂ ), 1.51 (pentet, 4H, J = 7 Hz, 2 x OCH ₂ CH ₂ ), 2.202 (t, 4H, J = 7.5 Hz, NCH ₂ ), 2.205 (s, 12H, NCH ₃ ), 3.17 (s, 4H, OCH ₂ ), 3.33 (t, 4H, J = 6.5 Hz ₁ OCH ₂ ); 10 ¹³ C NMR (CDCI ₃ ) δ 73.5 (CCH ₂ O), 71.53 (OCH ₂ ), 60.9 (NCH ₂ ), 45.7 (NCH ₃ ), 41.0 (qC), 32.1 (CH ₂ CH ₂ CH ₃ ), 29.85, 29.77, 29.70, 29.52 (5 decyl CH ₂ , CCH ₂ ), 26.5 (OCH ₂ CH ₂ CH ₂ ), 22.8 (CH ₂ CH ₃ ), 21.4 (NCH ₂ CH ₂ ), 14.3 (Me); HR ESI MS m/z calcd for C ₃₃ HnN ₂ O ₂ (M+H) 527.5510, found 527.5502.

Example 2OC 15 4,4-Bis(dodecyloxymethyl)-W,Λ/,Λr,Λf -tetramethyl-1 ,7-heptanediamine (20c)

[00216] Diamide 19c (Example 19C) (0.64 g, 1.0 mmol) is reacted with LiAIH ₄ (0.16 g, 4.2 mmol) following the procedure of Example 2OA to give the title compound as a light brown liquid: yield 0.55 g (90%); R _F on basic alumina 0.7 (DCM: methanol 93:7); ¹ H NMR

20 (CDCI ₃ ) δ 0.88 (t, 6H, J = 7.0 Hz, CH ₃ ), 1.21-1.33 (m, 40 H, 18 dodecyl CH ₂ , 2 CCH ₂ ), 1.37-1.43 (m, 4H, NCH ₂ CH ₂ ), 1.51 (pentet, 4H, J = 7 Hz, 2 x OCH ₂ CH ₂ ), 2.186 (t, 4H, J = 7.5 Hz, NCH ₂ ), 2.189 (s, 12H, NCH ₃ ), 3.17 (s, 4H, OCH ₂ ), 3.33 (t, 4H, J = 6.5 Hz, OCH ₂ ); 1 ³ C NMR (CDCI ₃ ) δ 73.5 (CCH ₂ O), 71.5 (OCH ₂ ), 60.9 (NCH ₂ ), 45.7 (NCH ₃ ), 40.9 (qC), 32.1 (CH ₂ CH ₂ CH ₃ ), 29.85, 29.82, 29.74, 29.52 (7 dodecyl CH ₂ , CCH ₂ ), 26.5 5 (OCH ₂ CH ₂ CH ₂ ), 22.8 (CH ₃ CH ₂ ), 21.4 (NCH ₂ CH ₂ ), 14.3 (Me); HR ESI MS m/z calcd for C ₃₇ H ₇₉ N ₂ O ₂ (M+H) 583.6136, found 583.6123. Example 2OD N,W,W,W-Tetramethyl-4,4-bis(tetradecyloxymethyl)-1,7-heptane diamine (20d)

2Od

[00217] Diamide 19d (Example 19D) (1.0 g, 1.5 mmol) is reacted with LiAIH ₄ (0.23 g, 6.0 mmol) following the procedure of Example 2OA to give the title compound as a light brown liquid: yield 0.60 g (68%); R _F on basic alumina 0.52 (dichloromethane: methanol 96:4); ¹ H NMR (CDCI ₃ ) δ 0.88 (t, 6H, J = 7.0 Hz, CH ₃ ), 1.21-1.35 (m, 48 H, 22 tetradecyl CH ₂ , 2 CCH ₂ ), 1.38-1.43 (m, 4H, NCH ₂ CH ₂ ), 1.51 (pentet, 4H, J = 7 Hz, 2 x OCH ₂ CH ₂ ), 2.209 (t, 4H, J = 7.5 Hz, NCH ₂ ), 2.211 (s, 12H, NCH ₃ ), 3.17 (s, 4H, OCH ₂ ), 3.33 (t, 4H, J = 6.5 Hz, OCH ₂ ); ¹³ C NMR (CDCI ₃ ) δ 73.5 (CCH ₂ O), 71.5 (OCH ₂ ), 60.9 (NCH ₂ ), 45.6 (NCH ₃ ), 40.9 (qC), 32.1 (CH ₂ CH ₂ CH ₃ ), 29.87, 29.77, 29.71 , 29.52 (9 tetradecyl CH ₂ , CCH ₂ ), 26.5 (OCH ₂ CH ₂ CH ₂ ), 22.9 (CH ₂ CH ₃ ), 21.4 (NCH ₂ CH ₂ ), 14.3 (Me); HR ESI MS m/z calcd for C ₄ i H ₈₇ N ₂ O ₂ (M+1) 639.6762, found 639.6744.

Example 21A W,tø,tø, W, W, W-Hexamethyl-4,4-bis(octyloxymethyl)-1 ,7-heptanediammonium diiodide (21a)

21a

[00218] Methyl iodide (1.51 g, 10.6 mmol) is added to a stirred solution of amine 20a (Example 20A) (0.5 g, 1.0 mmol) in THF (30 ml_). The reaction mixture is refluxed for 12 h, then concentrated. The solid residue is purified by flash column chromatography using 10 % methanol in dichloromethane as eluent to give the title compound as an off-white solid, yield: 0.75 g (94%); mp 233-236 ⁰ C; R _F 0.5 on basic alumina (7% methanol in dichloromethane); ¹ H NMR (CDCI ₃ ) δ 0.88 (t, 6H, J = 7.0 Hz, CH ₃ ), 1.23-1.31 (m, 20 H, 10 x CH ₂ ), 1.43 (m, 4H, J = 8.2 Hz NCH ₂ CH ₂ CH ₂ ), 1.51 (pentet, 4H, J = 6.5 Hz, 2 x OCH ₂ CH ₂ ), 1.88 (m, 4H, NCH ₂ CH ₂ ), 3.21 (s, 4H, OCH ₂ ), 3.36 (t, 4H, J = 6.5 Hz, OCH ₂ ), 3.44 (S ₁ 18H, NCH ₃ ), 3.73 (m, 2H, NCH ₂ ); ¹³ C NMR (CDCI ₃ ) δ 72.5 (CCH ₂ O), 71.6 (OCH ₂ ), 67.8 (NCH ₂ ), 54.5 (NCH ₃ ), 41.4 (qC), 32.0 (CH ₂ CH ₂ CH ₃ ), 29.82, 29.62, 29.53 (octyl CH ₂ ), 26.7 (CCH ₂ ), 26.5 (OCH ₂ CH ₂ CH ₂ ), 22.8 (CH ₃ CH ₂ ), 17.8 (NCH ₂ CH ₂ ), 14.3 (Me); HR ESI MS m/z calcd for C ₃ i H ₆₈ IN ₂ O ₂ (M-I) 627.4320, found 627.4267. Example 21 B

4,4-Bis(decyloxymethyl)-Λ/,Λ/,Λ/,Λr,Λ/\ΛT-hexamethy l-1,7-heptanediammonium diiodide (21b)

21 b

[00219] Alkylation of amine 20b (Example 20B) (0.5 g, 0.9 mmol) with methyl iodide (1.34 g, 9.43 mmol) following the procedure of Example 21 A gives the title product as an off-white solid: yield 0.70 g (91%); mp 240-243 ⁰ C; R _F 0.5 on basic alumina (7% methanol in dichloromethane); ¹ H NMR (CDCI ₃ ) δ 0.88 (t, 6H, J = 7.0 Hz, CH ₃ ), 1.23-1.33 (m, 28 H, 14 x CH ₂ ), 1.43 (m, 4H, NCH ₂ CH ₂ CH ₂ ), 1.51 (pentet, 4H, J = 6.5 Hz ₁ 2 x OCH ₂ CH ₂ ), 1.88 (m, 4H, NCH ₂ CH ₂ ), 3.22 (s, 4H ₁ OCH ₂ ), 3.37 (t, 4H ₁ J = 6.5 Hz ₁ OCH ₂ ), 3.45 (s, 18H, NCH ₃ ), 3.72 (m, 2H, NCH ₂ ); ¹³ C NMR (CDCI ₃ ) δ 72.5 (CCH ₂ O), 71.6 (OCH ₂ ), 67.8

(NCH ₂ ), 54.4 (NCH ₃ ), 41.4 (qC), 32.1 (CH ₂ CH ₂ CH ₃ ), 29.88, 29.79, 29.67, 29.50 (5 decyl CH ₂ ), 26.7 (CCH ₂ ), 26.5 (OCH ₂ CH ₂ CH ₂ ), 22.8 (CH ₃ CH ₂ ), 17.9 (NCH ₂ CH ₂ ), 14.3 (Me); HR ESI MS m/z calcd for C ₃₅ H ₇₆ IN ₂ O ₂ (M-I) 683.4946, found 683.4895.

Example 21 C 4,4-Bis(dodecyloxymethyl)-/V,/V,/V,W,/V,/V-hexamethyl-1,7-he ptanediammonium diiodide (21c)

1CH ₃

[00220] Alkylation of amine 20c (Example 20C) (0.50 g, 0.8 mmol) with methyl iodide (1.2 g, 8.4 mmol) following the procedure of Example 21 A gives the title product as an off-white solid: yield 0.65 g (88%); mp 252-254 ⁰ C; R _F 0.5 on basic alumina (7% methanol in dichloromethane); ¹ H NMR (CDCI ₃ ) δ 0.88 (t, 6H, J = 7.0 Hz, CH ₃ ), 1.22-1.34 (m, 20 H, 10 x CH ₂ ), 1.41 (m, 4H, NCH ₂ CH ₂ CH ₂ ), 1.51 (pentet, 4H, J = 6.5 Hz, 2 x OCH ₂ CH ₂ ), 1.87 (m, 4H, NCH ₂ CH ₂ ), 3.22 (s, 4H, OCH ₂ ), 3.37 (t, 4H, J = 6.5 Hz, OCH ₂ ), 3.46 (s, 18H, NCH ₃ ), 3.71 (m, 4H, 2H, NCH ₂ ); ¹³ C NMR (CDCI ₃ ) δ 72.5 (CCH ₂ O), 71.6 (OCH ₂ ), 67.8 (NCH ₂ ), 54.4 (NCH ₃ ), 41.3 (qC), 32.1 (CH ₂ CH ₂ CH ₃ ), 29.86, 29.82, 29.69, 29.51 (decyl CH ₂ ), 26.72, 26.48 (OCH ₂ CH ₂ CH ₂ ), 22.83 (CH ₃ CH ₂ ), 17.8 (NCH ₂ CH ₂ ), 14.3 (Me); HR ESI MS m/z calcd for C ₃₉ H ₈₄ IN ₂ O ₂ (M-I) 739.5572, found 739.5548.

Example 21 D Λ/,Λ/,/V,Λr,Λr,Λr-Hexamethyl-4,4-bis(tetradecyloxymethy l)-1,7-heptanediammonium d i iodide (21 d)

[00221] Alkylation of amine 2Od (Example 20D) (0.5 g, 0.9 mmol) with methyl iodide (0.89 g, 6.2 mmol) following the procedure of Example 21A gives the title product as an off-white solid: yield 0.51 g (88%); mp 238 - 241 ⁰ C; R _F 0.47 on basic alumina (8% methanol in dichloromethane); ¹ H NMR (CDCI ₃ ) δ 0.88 (t, 6H, J = 7.0 Hz, CH ₃ ), 1.22-1.32 (m, 44 H, 22 x CH ₂ ), 1.44 (m, 4H, NCH ₂ CH ₂ CH ₂ ), 1.51 (pentet, 4H, J = 6.5 Hz, 2 x OCH ₂ CH ₂ ), 1.89 (m, 4H, NCH ₂ CH ₂ ), 3.22 (s, 4H, OCH ₂ ), 3.37 (t, 4H, J = 6.5 Hz, OCH ₂ ), 3.44 (s, 18H, NCH ₃ ), 3.74 (m, 4H, NCH ₂ ); ¹³ C NMR (CDCI ₃ ) δ 72.4 (CCH ₂ O), 71.6 (OCH ₂ ), 67.8 (NCH ₂ ), 54.5 (NCH ₃ ), 41.3 (qC), 32.1 (OCH ₂ CH ₂ ), 29.87, 29.82, 29.70, 29.52 (decyl CH ₂ ), 26.61 , 26.48 (OCH ₂ CH ₂ CH ₂ ), 22.8 (CH3CH ₂ ), 17.9 (NCH ₂ CH ₂ ), 14.3 (Me); HR ESI MS m/z calcd for C ₄₃ H ₉₂ IN ₂ O ₂ , 795.6198, found 795.6215.

Example 22A

Sodium 2,2-bis(butyloxymethyl)-1,3-propanediol disulfate (22a)

2 ^2a [00222] NaH (60% oil dispersion, washed with hexanes, 7.15 g, 0.18 mol, 7.2 eq) is added to an ice cold DMF (100 ml_) solution of 1-butanol (4.15 g, 0.056 mol, 2.2 eq), and the reaction mixture is stirred for 1.5 h. A solution of pentaerythritol bicyclic sulfate (XIII, Scheme 5, prepared by the methods of Gulyas, H.; Dobό, A.; Bakos, J. Can. J. Chem. 5 2001, 79, 1040-1048 and/or Gulyas, H.; Arva, P.; Bakos, J. Chem. Commun. 1997, 2385-2386) (6.40 g, 0.025 mol) in DMF (50 mL) is added, followed, after 2 h, by an additional aliquot of NaH (60% oil dispersion, washed with hexanes, 2.06 g, 0.052 mol, 2.0 eq). After being stirred for 24 h at 60 ⁰ C, the reaction mixture is cooled to 0 ⁰ C and MeOH is added slowly dropwise until foaming ceased. 20% HCI is then added dropwise0 to neutralize (pH paper) the mixture. The reaction mixture is concentrated to give a brown solid which is recrystallized from 1 :19 water/MeOH to give the title compound (22a, 7.34 g, 0.016 mol, 65 %): recrystalized from methanol-ethyl acetate as colorless opaque needles: mp 200-203 ⁰ C, becomes transparent, 225°C starts turning brown, 245 - 25O ⁰ C; ¹ H NMR (DMSO-d ₆ ) δ 3.70 (s, 4H, -OSO ₃ CH ₂ C), 3.33 (t, 4H, J = 6.5 Hz ,5 OCH ₂ CH ₂ ), 3.29 (s, 4H, CCH ₂ ), 1.44 (p, 4H, J = 6.9 Hz, OCH ₂ CH ₂ ), 1.32 (sextet, 4 H, J = 7.3 Hz, CH ₂ CH ₂ CH ₃ ), 0.86 (t, 6H, J = 7.4 Hz, CH ₃ ); ¹³ C NMR δ 70.5 (OCH ₂ CH ₂ ), 69.4 (CCH ₂ ), 65.1 (-OSO ₃ CH ₂ ), 43.4 (q C), 31.3 (CH ₃ CH ₂ CH ₂ ), 18.4 (CH ₃ CH ₂ ), 13.8 (CH ₃ ); ESI MS m/z calc for C ₁₃ H ₂₇ O ₁₀ S ₂ : 407.10, found: 406.9; for C ₁₃ H ₂₆ O ₁₀ S ₂ Na: 429.09, found: 429.3; for (C ₁₃ H ₂₆ O ₁₀ S ₂ )/2: 203.05, found: 203.1. Anal. CaIc. for 0 C ₁₃ H ₂₈ O ₁₀ S ₂ Na ₂ -H ₂ O: C 33.19, H 6.00. Found: C 32.97, H 5.77.

Example 22B

Sodium 2,2-bis(hexyloxymethyl)-1,3-propanediol disulfate (22b)

22b

[00223] A hexanes-washed 60% oil dispersion of NaH (5.20 g, 0.13 mol, 2.8 eq) is5 added to an ice cold DMF (200 mL) solution of 1-hexanol (4.68 g, 0.046 mol, 2.1 eq) then the mixture is stirred for 30 min. A DMF (25 mL) solution of the bicyclic sulfate XIII (Scheme 5, prepared by the methods of Gulyas, H.; Dobό, A.; Bakos, J. Can. J. Chem. 2001, 79, 1040-1048 and/or Gulyas, H.; Arva, P.; Bakos, J. Chem. Commun. 1997, 2385-2386) (5.60 g, 0.022 mol) is added to the ice cold reaction mixture, followed after 20 h, by an additional aliquot of hexanes-washed NaH (4.40 g, 0.11 mol, 2.4 eq). After being stirred for 48 h at rt, the reaction mixture is cooled to O ⁰ C and MeOH is added slowly dropwise until foaming ceased. 5% HCI is then added dropwise to neutralize (pH paper) the mixture. The mixture is then concentrated to give a yellow solid which is recrystallized with a 1 :19 water/MeOH solvent system to give the title compound (6.63 g, 0.0215 mol, 61%). The analytical sample is recrystallized from methanol: mp 185-187°C; ¹ H NMR (DMSO-Cf ₆ ) δ 3.70 (s, 4H, -OSO ₃ CH ₂ C), 3.32 (t, 4H, J = 6.5 Hz , OCH ₂ CH ₂ ), 3.29 (s, 4H, CCH ₂ ), 1.46 (p, 4H, J = 6.7 Hz, OCH ₂ CH ₂ ), 1.23-1.32 ( complex m, 12 H, 2 x (CHz) ₃ ), 0.86 (t, 6H, J = 6.9 Hz, CH ₃ ); ¹³ C NMR δ 70.8 (OCH ₂ CH ₂ ), 69.4 (CCH ₂ ), 65.1 (- OSO ₃ CH ₂ ), 43.4 (q C), 31.1 (CH ₃ CH ₂ CH ₂ ), 29.1 (OCH ₂ CH ₂ ), 25.3 (OCH ₂ CH ₂ CH ₂ ), 22.1 (CH ₃ CH ₂ ), 13.9 (CH ₃ ); ESI MS m/z calc for C ₁₇ H ₃₅ O ₁₀ S ₂ : 463.17, found: 462.9; for C ₁₇ H ₃₄ O ₁₀ S ₂ Na: 485.15, found: 485.3; for (C ₁₇ H ₃₄ O ₁₀ S ₂ )/2: 231.08, found: 231.2. Anal. CaIc. for C ₁₇ H ₃₆ O ₁₀ S ₂ Na ₂ H ₂ O: C 38.78, H 6.89. Found: C 38.29, H 6.92.

Example 22C

Sodium 2,2-bis(octyloxymethyl)-1,3-propanediol disulfate (22c)

2 ^2c

[00224] A 60% oil dispersion of sodium hydride (6.08 g, 6.6 eq, 0.152 mol) is washed exhaustively with dried hexanes then added to an ice cold DMF (200 ml.) solution of 1- octanol (6.60 g, 2.2 eq, 0.0506 mol). The solution is left to stir under N ₂ and in an ice bath for 20 min. A DMF solution (50 ml.) of the bicyclic sulfate XIII (Scheme 5, prepared by the methods of Gulyas, H.; Dobό, A.; Bakos, J. Can. J. Chem. 2001, 79, 1040-1048 and/or Gulyas, H.; Arva, P.; Bakos, J. Chem. Commun. 1997, 2385-2386) (6.00 g, 0.0230 mol) is added slowly dropwise to the ice cold mixture over a 15 min period. The mixture is then allowed to slowly reach room temperature and left to stir for 24 h. MeOH is added dropwise to an ice cold reaction mixture until no more gas is formed. This is followed by dropwise addition of 20% H ₂ SO ₄ until a neutral (pH paper) solution is obtained. Concentration gives a yellow viscous liquid which is extracted with boiling MeOH (~1.5 L). A concentrated extract is allowed to undergo water promoted crystallization. The title compound (9.40 g, 72.3%) is a white powder with complex melting behavior: at 37.3°C softening occurs and the sample becomes slightly transparent, at 108.0 ⁰ C, it solidifies and becomes more opaque, at 159.8 ⁰ C, it becomes increasingly opaque, at 167.1 ⁰ C, it softens and becomes transparent, at 184.9°C, it melts; R _F 0.53 (butanol: water: methanol 10:5:2); ¹ H NMR (DMSO-Cf ₆ ) δ 3.71 (s, 4H, -OSO ₃ CH ₂ ), 3.31 (t, 4H, J = 6.5 Hz, OCH ₂ CH ₂ ), 3.29 (s, 4H, CCH ₂ ), 1.46 (p, 4H, J = 7.0 Hz, OCH ₂ CH ₂ ), 1.22-1.31 (complex m, 20 H, 2 x (CH ₂ ) ₅ ), 0.85 (t, 6H, J = 7.0 Hz, CH ₃ ); ¹³ C NMR δ 70.8 (OCH ₂ CH ₂ ), 69.3 (CCH ₂ ), 65.3 (-OSO ₃ CH ₂ ), 43.4 (q C), 31.3 (CH ₃ CH ₂ CH ₂ ), 29.2 (OCH ₂ CH ₂ ), 28.9, 28.7 (2 alkyl C), 25.7 (OCH ₂ CH ₂ CH ₂ ), 22.1 (CH ₃ CH ₂ ), 14.0 (CH ₃ ); ESI MS m/z calc for C ₂₁ H ₄₃ O ₁₀ S ₂ : 519.23, found: 519.1 ; for C ₂₁ H ₄₂ O ₁₀ S ₂ Na: 541.21 , found 541.3; for (C ₂₁ H ₄₂ O ₁₀ S ₂ )/2: 259.11 , found: 259.3. Anal. CaIc. for C ₂₁ H ₃₂ O ₁₀ S ₂ Na ₂ : C 44.67, H 7.50. Found: C, 44.18, H 7.84. Example 22D

Sodium 2,2-bis(decyloxymethyl)-1,3-propanediol disulfate (22d)

22d

[00225] A 60% oil dispersion of sodium hydride (5.53 g, 6.6 eq, 0.138 mol) is washed exhaustively with dried hexanes then added to an ice cold solution of 1-decanol (6.60 g, 2.2 eq, 0.0461 mol) in DMF (200 ml_). The mixture is left to stir in an ice bath under N ₂ for 20 min and then a solution of the bicyclic sulfate (XIII, Scheme 5, prepared by the methods of Gulyas, H.; Dobό, A.; Bakos, J. Can. J. Chem. 2001, 79, 1040-1048 and/or Gulyas, H.; Λrva, P.; Bakos, J. Chem. Commun. 1997, 2385-2386) (5.45 g, 0.0209 mol) in DMF (50 mL) is added dropwise over 30 min. The mixture is then allowed to reach room temperature and left to stir for 24 hrs. The reaction mixture is cooled in an ice bath, then methanol is added dropwise until gas evolution ceased. The solution is neutralized with 20% H ₂ SO ₄ (pH paper). Concentration gives a yellow viscous liquid which is extracted with boiling MeOH (-1.5 L). A concentrated extract is allowed to undergo water promoted crystallization. The title compound (7.60 g, 58.4%) is a colourless powder. Complex melting behavior is observed: at 38.0 ⁰ C, it softens and becomes slightly transparent, at 62.O ⁰ C, it becomes a white translucent paste, at 105.0 ⁰ C, an opaque white liquid, and at 196.0°C, it melts; R _F 0.55 (butanol: water: methanol 10:5:2); ¹ H NMR (DMSO-Cf ₆ ) δ 3.70 (s, 4H, -OSO ₃ CH ₂ C), 3.31 (t, 4H, J = 6.5 Hz , OCH ₂ CH ₂ ), 3.28 (s, 4H, CCH ₂ ), 1.46 (quintet, 4H, J = 6.5 Hz, OCH ₂ CH ₂ ), 1.21-1.33 (complex m, 28 H, 2 x (CH ₂ ) ₇ ), 0.85 (t, 6H, J = 6.5 Hz, CH ₃ ); ¹³ C NMR δ 70.8 (OCH ₂ CH ₂ ), 69.4 (CCH ₂ O), 65.3 (OSO ₃ CH ₂ ), 43.4 (q C), 31.3 (CH ₃ CH ₂ CH ₂ ), 29.16 (OCH ₂ CH ₂ ), 29.12, 29.03, 28.92, 28.74 (4 alkyl C), 25.7 (OCH ₂ CH ₂ CH ₂ ), 22.1 (CH ₃ CH ₂ ), 14.0 (CH ₃ ); ESI MS m/z calc for C ₂₅ H ₅ iO ₁₀ S ₂ : 575.29, found: 575.1 ; for C ₂₅ H ₅₀ O ₁₀ S ₂ Na: 597.27, found: 597.5; for (C ₂₅ H ₅ o0 ₁₀ S ₂ )/2: 287.14, found: 287.3. Anal. CaIc. for C ₂₅ H ₅₀ O ₁₀ S ₂ Na ₂ : C 48.38, H 8.12. Found: C 48.37, H 8.15.

Example 22E

Sodium 2,2-bis(dodecyloxymethyl)-1,3-propanediol disulfate (22e)

₁ CH ₃

22e

A 60% oil dispersion of sodium hydride (2.20 g, 10.5 eq, 0.093 mol) is washed exhaustively with dried hexanes then added to an ice cold solution of 1-dodecanol (3.49 g, 2.1 eq, 0.0186 mol) in DMF (50 ml_). The flask is flushed with N ₂ and the solution is left to stir in an ice bath for 2 h. A solution (10 ml.) of the bicyclic sulfate (XIII, Scheme 5, prepared by the methods of Gulyas, H.; Dobό, A.; Bakos, J. Can. J. Chem. 2001, 79, 1040-1048 and/or Gulyas, H.; Arva, P.; Bakos, J. Chem. Commun. 1997, 2385-2386) (2.35 g, 0.0209 mol) in DMF (10 ml.) is added to the ice cold mixture. The mixture is allowed to reach room temperature and left to stir for 5 h before additional NaH oil dispersion (1.90 g) is added. After 48 h, MeOH is added dropwise to an ice cold reaction mixture until gas evolution ceased. The reaction mixture is neutralized with 20% H ₂ SO ₄ (pH paper). Concentration gives a yellow viscous liquid which is extracted with boiling MeOH (~1.5 L). The solid residue obtained after removal of the MeOH is dissolved in water (100 mL) and extracted with CH ₂ CI ₂ (50 ml_). The water layer is concentrated to give a white solid that is crystallized from 10% H ₂ O in MeOH. The title compound (2.1Og, 14%) is collected as a colourless powder: complex melting behavior is observed; at 52.O ⁰ C, it softens, at 102.6°C, it becomes a slightly transparent solid, at 116.2°C, a colourless opaque fluid, at 141.3 ⁰ C, an increasingly transparent semi-solid, at 181.3°C, it melts; R _F 0.58 (butanol: water: methanol 10:5:2); ¹ H NMR (DMSO-Cf ₆ ) δ 3.69 (s, 4H, - OSO ₃ CH ₂ ), 3.31 (t, 4H, J = 6.5 Hz, OCH ₂ CH ₂ ), 3.28 (s, 4H, CCH ₂ ), 1.46 (p, 4H, J = 6.5 Hz, OCH ₂ CH ₂ ), 1.21-1.32 (complex m, 36 H, 2 x (CH ₂ ) ₉ ), 0.85 (t, 6H, J = 7.0 Hz, CH ₃ ); ¹³ C NMR δ 70.8 (OCH ₂ CH ₂ ), 69.4 (CCH ₂ ), 65.3 (-OSO ₃ CH ₂ ), 43.4 (q C), 31.4 (CH ₃ CH ₂ CH ₂ ), 30.7, 29.2, 29.2, 29.2, 29.1 , 29.9, 29.0, 28.8 (alkyl CH ₂ ), 25.7

(OCH ₂ CH ₂ CH ₂ ), 22.2 (CH ₃ CH ₂ ), 14.0 (CH ₃ ); ESI MS m/z calc for C ₂₉ H ₅₉ O ₁₀ S ₂ : 631.35, found: 631.2; for C ₂₉ H ₅₈ O ₁₀ S ₂ Na: 653.34, found: 553.5; for (C ₂₉ H ₅₈ O ₁₀ S ₂ )^: 315.17, found: 315.3. Anal. CaIc. for C ₂₉ H ₅₈ O ₁₀ S ₂ Na ₂ : C 51.46, H 8.54. Found: C 51.40, H 8.76.

Example 22F

Sodium 2,2-bis(tetradecyloxymethyl)-1,3-propanediol d is u If ate (22f)

5 ^22f

[00226] NaH (4.70 g, 60% oil dispersion, 6.6 eq, 0.1175 mol) is washed exhaustively with dried hexanes then added to an ice cold solution of 1-tetradecanol (8.40 g, 2.2 eq, 0.0392 mol) in DMF (200 ml_). The solution is flushed with N ₂ and left to stir in an ice bath for about 20 min. A DMF solution (50 mL) of the bicyclic sulfate (XIII, Scheme 5,

10 prepared by the methods of Gulyas, H.; Dobό, A.; Bakos, J. Can. J. Chem. 2001, 79, 1040-1048 and/or Gulyas, H.; Λrva, P.; Bakos, J. Chem. Commun. 1997, 2385-2386) (4.63 g, 0.0178 mol) is added slowly dropwise to the ice cold mixture over a 30 min period and then the temperature is allowed to rise slowly to rt. The reaction is monitored by recording NMR spectra of aliquots using singlets at ~5.00 ppm and -4.70 ppm to

15 monitor bicyclic sulfate and monoproduct, respectively. If reaction is still incomplete after 72 h, the reaction mixture is warmed to 45°C for 2h before being quenched by dropwise addition of MeOH. 20% H ₂ SO ₄ is added to neutralize the reaction mixture. Concentration gives a colourless viscous liquid which is extracted with boiling MeOH (1.5 L). The extract is concentrated. On trituration with water, the residue solidified to a white powder

20 (9.7g, 74.6%): mp 195 ⁰ C; R _F 0.60 (butanol: water: methanol 10:5:2); ¹ H NMR (DMSO- d6) δ 3.71 (s, 4H, -OSO ₃ CH ₂ ), 3.31 (t, 4H, J = 6.5 Hz, OCH ₂ CH ₂ ), 3.29 (s, 4H, CCH ₂ O), 1.47 (p, 4H, J = 6.5 Hz, 2 OCH ₂ CH ₂ ), 1.21-1.32 (complex m, 44 H, 2 x 11 CH ₂ ), 0.85 (t, 6H, J = 7.0 Hz, 2 CH ₃ ); ¹³ C NMR δ 70.7 (OCH ₂ CH ₂ ), 69.3 (CCH ₂ O), 65.2 (-OSO ₃ CH ₂ ), 43.3 (q C), 31.3 (CH ₃ CH ₂ CH ₂ ), 29.14, 29.11 , 29.09, 29.05, 29.04, 28.92, 28.72 (alkyl C),

25 25.7 (OCH ₂ CH ₂ CH ₂ ), 22.1 (CH ₃ CH ₂ ), 13.9 (CH ₃ ); ESI MS m/z calc for C ₃₃ H ₆₆ O ₁₀ S ₂ Na: 709.40, found: 709.6. Anal. CaIc. for C ₃₃ H ₆₆ O ₁₀ S ₂ Na ₂ : C 54.08, H 9.08. Found: C, 53.72, H 9.00. Example 23A

Sodium 5,5-bis(octyloxymethyl)-3,7-dioxa-1,9-nonanediol disulfate (23a)

23a

[00227] To a stirred ice-bath cooled solution of 2,2-bis(octyloxymethyl)-1,3-propanediol 5 2a (Example 2A) (5.40 g, 0.015 mol) in THF (100 mL) is added a hexanes-washed 60% oil dispersion of sodium hydride (2.60 g, 0.065 mol, 4.3 eq). The cooled reaction mixture is stirred for 30 min, then a solution of ethylene sulfate (prepared by the method of Baker, W.; Field, F. B. J. Chem. Soc. 1932, 86-91 and/or Brimacombe, J. S.; Foster, A. B.; Hancock, E. B.; Overend, W. G.; Stacey, M. J.Chem. Soc. 1960, 201-211) (4.0 g,

10 0.032 mol, 2.2 eq) in THF (50 mL) is added dropwise to the reaction mixture over a 20 min period. The reaction mixture is stirred for 19 h at rt, then MeOH is added carefully dropwise until foaming ceased. 10% HCI is added to neutralize the reaction (pH paper). Concentration gives a white paste that is purified using column chromatography with a solvent gradient changing from pure EtOAc to MeOH : EtOAc 2:3. The product is

15 obtained as a white solid (6.87 g, 70.2%): mp 143.0-145.5 ⁰ C, ¹ H NMR (500.13 MHz, MeOD: CDCI ₃ , 50:50) δ 0.89 (t, J = 6.8 Hz, 6H, 2 x CH ₃ ), 1.31 (br m, 2OH, alkyl protons), 1.54 (quintet, J = 7.0 Hz, 4H, 2 x OCH ₂ CH ₂ ), 3.38 (s, 4H, CH ₂ CH ₂ CH ₂ OCH ₂ C), 3.39 (t, J = 6.5Hz, 4H, 2 x OCH ₂ CH ₂ ), 3.49 (s, 4H, O ₃ SOCH ₂ CH ₂ OCH ₂ C), 3.68 (XX' part of AA ¹ XX' pattern, J _AX + J _AX = 10.0 Hz, 4H, 2 x O ₃ SOCH ₂ CH ₂ ), 4.14 (AA' part of AA'XX' pattern, J _AX

20 + J _A - _X = 10.0 Hz, 4H, 2 x O ₃ SOCH ₂ CH ₂ ); ¹³ C NMR (125.77 MHz, MeOD) δ 14.3 (2 x CH ₃ ), 23.2 (2 x CH ₂ CH ₃ ), 26.8 ( 2 x OCH ₂ CH ₂ CH ₂ ), 30.0, 30.1 , 30.2 (2 x OCH ₂ CH ₂ and alkyl chain carbons), 32.5 (2 x CH ₂ CH ₂ CH ₃ ), 46.3 (q C), 67.6 (2 x OSO ₃ CH ₂ ), 70.1 (2 x CH ₂ OCH ₂ CH ₂ CH ₂ ), 70.7 (2 x OSO ₃ CH ₂ CH ₂ ), 71.1 (2 x O ₃ SOCH ₂ CH ₂ OCH ₂ ), 72.4 (2 x OCH ₂ CH ₂ CH ₂ ); ESI MS (neg ion mode): calc for C ₂₅ H ₅₀ O ₁₂ S ₂ Na (M-Na) 629.26, found

25 629.3; calc for (M-2Na)/2 303.14, found 303.3, calc for M-2Na+H 607.28, found 607.1; calc for 2M-Na 1281.52, found 1281.1. Anal. Calc. for C ₂₅ H ₅₀ O ₁₂ S ₂ Na ₂ : C 46.00, H 7.72. Found: C 46.11 , H 7.47. Example 23B

Sodium 5,5-bis(decyloxymethyl)-3,7-dioxa-1,9-nonanediol disulfate (23b)

23b

[00228] A solution of 2,2-bis(decyloxymethyl)-1 ,3-propanediol 2b (Example 2B) (6.86 g, 5 0.0166 mol) in THF (100 mL) is cooled in an ice-bath and then hexane-washed sodium hydride (60% oil dispersion, 2.20 g, 0.055 mol, 3.3 eq) is added. After the cooled reaction mixture has stirred for 30 min, a THF (50 mL) solution of ethylene sulfate (prepared by the method of Baker, W.; Field, F. B. J. Chem. Soc. 1932, 86-91 and/or Brimacombe, J. S.; Foster, A. B.; Hancock, E. B.; Overend, W. G.; Stacey, M. J. Chem.

10 Soc. 1960, 201-211) (4.5 g, 0.036 mol, 2.2 eq) is added dropwise over a 20 min period. The cooling bath is removed and the reaction mixture is stirred for 24 hrs. MeOH is added carefully dropwise until foaming ceased. 10% HCI is added to neutralize the reaction (wet pH paper), then the reaction mixture is concentrated to a white paste. The product is crystallized from EtOAc:MeOH 75:25: yield; mp 165-172°C; ¹ H NMR (500.13

15 MHz, DMSO) δ 0.84 (t, J = 6.5 Hz, 6H, 2 x CH ₃ ), 1.24 (br m, 28H, alkyl protons), 1.46 (quintet, J = 7.2 Hz, 4H, 2 x OCH ₂ CH ₂ ), 3.26 (s, 4H, 2 x CH ₂ CH ₂ CH ₂ OCH ₂ C), 3.38 (s, 4H, 2 x O ₃ SOCH ₂ CH ₂ OCH ₂ C), 3.39 (t, J = 6.6 Hz, 4H, 2 x OCH ₂ CH ₂ ), 3.47 (XX ¹ part of AA'XX ¹ pattern, J _AX + J _AX = 10.0 Hz, 4H, 2 x O ₃ SOCH ₂ CH ₂ ), 3.77 (AA ¹ part of AA ¹ XX' pattern, J _AX + J _AX = 10.0 Hz, 4H, 2 x O ₃ SOCH ₂ CH ₂ ); ¹³ C NMR (125.77 MHz, MeOD) δ

20 13.9 (2 x CH ₃ ), 22.1 (2 x CH ₂ CH3), 25.6 ( 2 x OCH ₂ CH ₂ CH ₂ ), 28.7, 28.8, 29.0, 29.0, 29.1 (2 x OCH ₂ CH ₂ and 14 alkyl chain carbons), 31.3 (2 x CH ₂ CH ₂ CH ₃ ), 45.1 (q C), 64.8 (2 x OSO ₃ CH ₂ ), 68.9 (2 x CH ₂ OCH ₂ CH ₂ CH ₂ ), 69.6 (2 x OSO ₃ CH ₂ CH ₂ ), 70.0 (2 x OSO ₃ CH ₂ CH ₂ OCH ₂ ), 70.7 (2 x OCH ₂ CH ₂ CH ₂ ). Anal. CaIc. for C ₂₉ H ₅₈ Oi ₂ S ₂ Na ₂ : C 49.14, H 8.25. Found: C 49.36, H 8.38. Example 23C

Sodium 5,5-bis(dodecyloxymethyl)-3,7-dioxa-1,9-nonanediol disulfate (23c)

23c

[00229] To an ice-bath cooled solution of 2,2-bis(dodecyloxymethyl)-1 ,3-propanediol 2c (Example 2C) (7.08 g, 0.015 mol) in THF (100 ml_) is added a hexanes-washed 60% oil dispersion of NaH (2.20 g, 0.055 mol, 3.6 eq). The cooled reaction mixture is stirred for 30 min then a solution of ethylene sulfate (prepared by the method of Baker, W.; Field, F. B. J. Chem. Soc. 1932, 86-91 and/or Brimacombe, J. S.; Foster, A. B.; Hancock, E. B.; Overend, W. G.; Stacey, M. J.Chem. Soc. 1960, 201-211) (4.0 g, 0.032 mol, 2.2 eq) in THF (50 mL) is added dropwise over a 20 min period. After the reaction mixture has been stirred for 21 h at rt, not all starting material has been consumed (TLC). More ethylene sulfate (0.1 g, 0.8 mmol) is added and the reaction mixture is stirred for another 3 h. MeOH is added carefully dropwise until foaming ceases, then 10% HCI is added until the reaction mixture is neutral (pH paper). Concentration yields a white paste that is taken up in a 1 :1 CH ₂ CI ₂ /Me0H. The mixture is heated to a boil then filtered. The filtrate is then heated until the mixture became clear. The solution is allowed to cool to rt before being refrigerated. The product is collected by filtration (9.53 g, 0.0125 mol, 83.3%): mp 144.5 - 146.0 ⁰ C; ¹ H NMR (500.13 MHz, MeOD) δ 0.90 (t, J = 7.1 Hz, 6H, 2 x CH ₃ ), 1.29 (br m, 36H, alkyl protons), 1.54 (quintet, J = 7.2 Hz, 4H, 2 x OCH ₂ CH ₂ ), 3.38 (s, 4H, 2 x CH ₂ CH ₂ CH ₂ OCH ₂ C), 3.39 (t, J = 6.6 Hz, 4H, 2 x OCH ₂ CH ₂ CH ₂ ), 3.47 (s, 4H,

0 ₃ SOCH ₂ CH ₂ OCH ₂ C), 3.64 (AA' part of AA'XX ¹ pattern, J _AX + J _AX = 10.0 Hz, 4H, 2 x ^" O ₃ SOCH ₂ CH ₂ ), 4.09 (XX' part of AA'XX' pattern, J _AX + J _AX = 10.0 Hz, 4H, 2 x ^" O ₃ SOCH ₂ CH ₂ ); ¹³ C NMR (125.77 MHz, MeOD) δ 14.6 (2 x CH ₃ ), 23.9 (2 x CH ₂ CH ₃ ), 27.6 (2 x OCH ₂ CH ₂ CH ₂ ), 30.6, 30.8, 30.9, 30.9, 31.0 (2 x OCH ₂ CH ₂ and 12 alkyl chain carbons), 33.2 (2 x CH ₂ CH ₂ CH ₃ ), 47.0 (q C), 68.3 (2 x OSO ₃ CH ₂ ), 70.7

(CH ₂ OCH ₂ CH ₂ CH ₂ ), 71.3 (2 x OSO ₃ CH ₂ CH ₂ ), 71.4 (2 x OSO ₃ CH ₂ CH ₂ OCH ₂ ), 72.7 (2 x OCH ₂ CH ₂ CH ₂ ); ESI MS (neg ion mode): calc for (M+Na) m/z C ₃₃ H ₆₆ O ₁₂ S ₂ Na 741.39, found 741.5; calc for (M)/2, 359.20, found 359.3; calc for M +H, 719.40, found 719.2; calc for 2M+Na, 1505.77, found 1506.3. Anal. Calc. for C ₃₃ H ₆₄ O ₁₂ S ₂ Na ₂ : C 51.81 , H 8.70. Found: C 52.04, H 8.86. Example 23D

Sodium 5,5-bis(tetradecyloxymethyl)-3,7-dioxa-1 ,9-nonanediol disulfate (23d)

23d

[00230] To an ice-bath cooled solution of 2,2-bis(tetradecyloxymethyl)-1 ,3-propanediol 5 2d (Example 2D) (2.5 g, 0.0047 mol) in THF (75 mL) is added a hexanes-washed 60%

011 dispersion of NaH (1.0 g, 0.0236 mol, 5.0 eq ). The cooled reaction mixture is stirred for 30 min then a solution of ethylene sulfate (prepared by the method of Baker, W.; Field, F. B. J. Chem. Soc. 1932, 86-91 and/or Brimacombe, J. S.; Foster, A. B.; Hancock, E. B.; Overend, W. G.; Stacey, M. J.Chem. Soc. 1960, 201-211) (1.29 g,

10 0.0104 mol, 2.2 eq) in THF (20 mL) is added dropwise. When the addition is complete, the reaction mixture is heated to 4O ⁰ C, then stirred for 24 h. After 24 h, more NaH (0.19g 1.Oeq ) and ethylene sulfate (0.645 g, 0.005 mol, 1.1 eq) are added at 0 ⁰ C, then the reaction mixture is allowed to warm to 40 ⁰ C and then stirred for another 24 h. MeOH is added carefully dropwise until foaming ceases, then 10% HCI is added until the reaction

15 mixture is neutral (pH paper). Concentration yields a light yellow solid that is purified using flash column chromatography eluting with ethyl acetate-methanol mixtures changing from 95: 05 to 80:20 to afford the title compound (23d) as a colorless powder, that is precipitated by addition of water and then recrystallized from ethyl acetate methanol to yield a colorless crystalline product: yield: 2.34 g, 60.3 %; mp 145°C,

20 became transparent, 160°C melted; ¹ H NMR (500.13 MHz, MeOD) δ 0.90 (t, J = 7.5 Hz, 6H, 2 x CH ₃ ), 1.29 (br m, 4OH, alkyl protons), 1.54 (quintet, J = 6.5 Hz, 4H, 2 x OCH ₂ CH ₂ ), 3.35 (s, 4H, 2 x CH ₂ CH ₂ CH ₂ OCH ₂ C), 3.39 (t, J = 6.5 Hz, 4H, 2 x OCH ₂ CH ₂ CH ₂ ), 3.46 (s, 4H, O ₃ SOCH ₂ CH ₂ OCH ₂ C), 3.64 (AA ¹ part of AA ¹ XX' pattern, J _AX + J _A . _X = 10.0 Hz, 4H, 2 x O ₃ SOCH ₂ CH ₂ ), 4.09 (XX ¹ part of AA ¹ XX ¹ pattern, J _AX + J _A χ =

25 10.0 Hz, 4H, 2 x O ₃ SOCH ₂ CH ₂ ); ¹³ C NMR (125.77 MHz, MeOD) δ 14.4 (2 x CH ₃ ), 23.7 (2 x CH ₂ CH ₃ ), 27.4 (2 x OCH ₂ CH ₂ CH ₂ ), 30.5, 30.6, 30.8, 30.8, 30.8 (2 x OCH ₂ CH ₂ and

12 alkyl chain carbons), 33.1 (2 x CH ₂ CH ₂ CH ₃ ), 46.8 (q C), 68.1 (2 x OSO ₃ CH ₂ ), 70.5 (CH ₂ OCH ₂ CH ₂ CH ₂ ), 71.2 (2 x OSO ₃ CH ₂ CH ₂ ), 71.3 (2 x OSO ₃ CH ₂ CH ₂ OCH ₂ ), 72.5 (2 x OCH ₂ CH ₂ CH ₂ ); HRMS calc for (M-Na) C ₃₇ H ₇₄ O ₁₂ S ₂ Na 797.452, found 797.442. Example 24A

Disodium 6,6-bis(octyloxymethyl)-4,8-dioxa-1 ,11 -undecanedisulfonate

24a

[00231] 1 ,3-Propanesultone (4.1 mL, 10 eq.) in THF (5 mL) is added to a stirred solution 5 of 2,2-bis(octyloxymethyl)-1 ,3-propanediol (Compound 2a, Example 2A) (1.7 g, 4.7 mmol) in THF (5 mL) under an Ar atmosphere and then a suspension of hexane-washed sodium hydride (60% oil dispersion, 0.43 g, 10.6 mmol, 2.25 eq) in THF (3 mL) is added dropwise over a 20-30 min. period. The resulting mixture is stirred for 18 h at 4O ⁰ C. Another addition of a suspension of sodium hydride (60% oil dispersion, 0.21 g, 5.34

10 mmol, 1.13 eq) in THF (3 mL) is made and the reaction mixture is stirred for an additional 6 h at 40 ⁰ C, then for 24 h at it Methanol is added dropwise to the ice-bath cooled reaction mixture until foaming ceases. 10% HCI is added until the reaction mixture is neutral (pH paper). Concentration gave a white solid that is purified using flash column chromatography initially eluting with an ethyl acetate / ethanol mixture (80:20 v:v) and

15 then eluting with ethanol / ethyl acetate (80:20 v:v) to afford the title compound as a white solid that is precipitated out from ethanol / water and then recrystallized from ethyl acetate / methanol to yield colorless granules: yield 2.31 g, 76 %; mp 185°C becomes transparent, 220-235°C, decomposes; R _F 0.34 (butanol water methanol: 10 2.5 1.5); ¹ H NMR (500.13 MHz, methanol-d ₄ ) δ 0.90 (t, J = 6.9 Hz, 6H, 2 x CH ₃ ), 1.31 (br m, 2OH,

20 alkyl protons), 1.52 (pentet, J = 6.7 Hz, 4H, 2 x OCH ₂ CH ₂ CH ₂ CH ₂ ), 2.02 (m, 4H, 2 x O ₃ SCH ₂ CH ₂ ), 2.87 (m, 4H, 2 x O ₃ SCH ₂ ), 3.36 (s, 4H, 2 x CH ₂ CH ₂ CH ₂ CH ₂ OCH ₂ C), 3.377 (t, 4H, J = 6.3 Hz, 2 x OCH ₂ CH ₂ CH ₂ ), 3.383 (s, 4H, 2 x O ₃ SCH ₂ CH ₂ CH ₂ OCH ₂ C), 3.48 (t, 4H, J = 6.1 Hz, 2 x O ₃ SCH ₂ CH ₂ CH ₂ ); ¹³ C NMR (125.77 MHz, methanol-cf ₄ ) δ 14.4 (2 x CH ₃ ), 23.7 (2 x CH ₂ CH ₃ ), 23.7 (2 x O ₃ SCH ₂ CH ₂ ), 26.7 (2 x OCH ₂ CH ₂ CH ₂ ),

25 27.4, 30.47, 30.54, 30.74 (2 x OCH ₂ CH ₂ and alkyl chain carbons), 33.0 (2 x

CH ₂ CH ₂ CH ₃ ), 46.7 (q C), 50.0 (2 x O ₃ SCH ₂ ), 70.7 (2 x CH ₂ OCH ₂ CH ₂ CH ₂ CH ₂ ), 70.9 (2 x O ₃ SCH ₂ CH ₂ CH ₂ OCH ₂ ), 71.2 (2 x O ₃ SCH ₂ CH ₂ CH ₂ O), 72.5 (OCH ₂ CH ₂ CH ₂ CH ₂ ); HR ESI MS m/z calc for C ₂₇ H ₅₄ O ₁₀ S ₂ Na (M-Na) 625.3051, found 625.3082. Example 24B

Disodium 6,6-bis(decyloxymethyl)-4,8-dioxa-1 ,11 -undecanedisulfonate

24b

[00232] Compound 24b is made following the procedure of Example 24A except that workup of the neutralized reaction mixture is changed. 2,2-Bis(decyloxymethyl)-1 ,3- propanediol (Compound 2b, Example 2B) (1.72 g, 4.13 mmol) in THF (5 ml.) is reacted with 1 ,3 propanesultone (4.0 mL, 10 eq) under Ar using two additions of suspensions of hexane-washed 60% oil dispersions of sodium hydride (0.37 g, 9.3 mmol, 2.25 eq) in THF (3 mL) and (0.186 g, 5.17 mmol, 1.13 eq) in THF (3 mL). The colorless solid resulting from concentration of the neutralized reaction mixture is washed repeatedly with ethyl acetate until NMR indicated that all sultone has been removed. The product is then extracted with hot ethanol. The hot ethanol extract is concentrated then the residue is taken up in boiling ethanol containing a few drops of water. Cooling results in a precipitate that is crystallized from ethyl acetate / methanol to give colorless granules of the title compound: yield 2.4 g, 83 %; mp 187°C, becomes transparent, 215-230 ⁰ C decomposes; R _F 0.38 (butanol water methanol: 10 2.5 1.5); ¹ H NMR (500.13 MHz, methanol-c/ ₄ ) δ 0.89 (t, J = 6.9 Hz, 6H, 2 x CH ₃ ), 1.34 (br m, 28H, alkyl protons), 1.54 (pentet, J = 6.5 Hz, 4H, 2 x OCH ₂ CH ₂ CH ₂ CH ₂ ); 2.02 (m, 4H, 2 x O ₃ SCH ₂ CH ₂ ), 2.89 (m, 4H, 2 x O ₃ SCH ₂ ), 3.36 (s, 4H, 2 x CH ₂ CH ₂ CH ₂ CH ₂ OCH ₂ C), 3.377 (t, 4H, J = 6.3 Hz, 2 x OCH ₂ CH ₂ CH ₂ ), 3.382 (s, 4H, 2 x O ₃ SCH ₂ CH ₂ CH ₂ OCH ₂ C), 3.48 (t, 4H, J = 6.1 Hz, 2 x O ₃ SCH ₂ CH ₂ CH ₂ ); ¹ H NMR (500.13 MHz, DMSO-Cf ₆ ) δ 0.86 (t, J = 6.8 Hz, 6H, 2 x CH ₃ ), 1.24 (br m, 28H, alkyl protons), 1.46 (pentet, J = 6.6 Hz, 4H, 2 x OCH ₂ CH ₂ CH ₂ CH ₂ ), 1.77 (m, 4H, 2 x O ₃ SCH ₂ CH ₂ ), 2.44 (m, 4H, 2 x O ₃ SCH ₂ ), 3.255, 3.257 (2s, 8H, 2 x CH ₂ CH ₂ CH ₂ CH ₂ OCH ₂ C, 2 x O ₃ SCH ₂ CH ₂ CH ₂ OCH ₂ C), 3.31 (t, 4H, J = 6.4 Hz, 2 x O ₃ SCH ₂ CH ₂ CH ₂ ), 3.36 (t, 4H, J = 6.3 Hz, 2 x O ₃ SCH ₂ CH ₂ CH ₂ ); ¹³ C NMR (125.77 MHz, methanol-d ₄ ) δ 14.4 (2 x CH ₃ ), 23.7 (2 x CH ₂ CH ₃ ), 23.7 ( 2 x O ₃ SCH ₂ CH ₂ ), 26.7 (2 x OCH ₂ CH ₂ CH ₂ ), 27.4, 30.47, 30.58, 30.72, 30.81 (2 x OCH ₂ CH ₂ and alkyl chain carbons), 33.1 (2 x CH ₂ CH ₂ CH ₃ ), 46.7 (q C), 50.0 (2 x O ₃ SCH ₂ ), 70.7 (2 x CH ₂ O(CH ₂ ) ₉ ),

70.9 (2 x O ₃ SCH ₂ CH ₂ CH ₂ OCH ₂ ), 71.2 (2 x O ₃ SCH ₂ CH ₂ CH ₂ O), 72.5 (OCH ₂ (CH ₂ ) ₈ ); HR ESI MS m/z calcd for C _3I H ₆₂ NaO ₁₀ S ₂ (M-Na) 681.3677, Found 681 :3706.

Example 24C

Disodium 6,6-bis(dodecyloxymethyl)-4,8-dioxa-1,11-undecanedisulfonate

24c

[00233] Compound 24c is made following the procedure of Example 24B.

2,2-Bis(dodecyloxymethyl)-1 ,3-propanediol (Compound 2c, Example 2C) (1.32 g, 2.79 mmol) in THF (5 mL) is reacted with 1 ,3 propanesultone (2.5 mL, 28 mmol, 10 eq) in THF (5 mL) under Ar using two additions of suspensions of hexane-washed 60% oil dispersion of sodium hydride (0.25 g, 6.3 mmol, 2.25 eq) in THF (3 mL) and 1.13 eq in THF (3 mL). The colorless solid resulting from concentration of the neutralized reaction mixture is washed repeatedly with ethyl acetate until NMR indicates that all sultone had been removed. The product is then extracted with hot ethanol. The hot ethanol extract is concentrated then the residue is taken up in boiling ethanol containing a few drops of water. Cooling results in a precipitate that is crystallized from ethyl acetate / methanol to give colorless granules of the title compound: yield 1.80 g, 85 %; mp 18O ⁰ C, becomes transparent, 215-240 ⁰ C, decomposes; R _F 0.41 (butanol water methanol: 10 2.5 1.5); ¹ H NMR (500.13 MHz, methanol-d ₄ ) δ 0.89 (t, J = 6.9 Hz, 6H, 2 x CH ₃ ), 1.29-1.35 (br s, 36H, 18 x CH ₂ ), 1.56 (pentet, J = 6.6 Hz, 4H, 2 x OCH ₂ CH ₂ CH ₂ CH ₂ ); 2.02 (m, 4H, 2 x O ₃ SCH ₂ CH ₂ ), 2.87 (m, 4H, 2 x O ₃ SCH ₂ ), 3.36 (s, 4H, 2 x (CHz) ₁₁ OCH ₂ C), 3.377 (t, 4H, J = 6.3 Hz, 2 x OCH ₂ (CH ₂ ) ₁₀ ), 3.382 (s, 4H, 2 x O ₃ SCH ₂ CH ₂ CH ₂ OCH ₂ C), 3.48 (t, 4H, J = 6.1 Hz, 2 x O ₃ SCH ₂ CH ₂ CH ₂ ); ¹³ C NMR (125.77 MHz, MeOD) δ 14.5 (2 x CH ₃ ), 23.7 (2 x CH ₂ CH ₃ ), 23.7 (2 x O ₃ SCH ₂ CH ₂ ), 26.7 (2 x OCH ₂ CH ₂ CH ₂ ), 27.4, 30.49, 30.59, 30.65, 30.78, 30.82 (2 x OCH ₂ CH ₂ and alkyl chain carbons), 33.1 (2 x CH ₂ CH ₂ CH ₃ ), 46.7 (q C), 50.0 (2 x O ₃ SCH ₂ ), 70.7 (2 x CH ₂ O(CH ₂ ) _H ), 70.9 (2 x O ₃ SCH ₂ CH ₂ CH ₂ OCH ₂ ), 71.2 (2 x O ₃ S(CH ₂ ) ₂ CH ₂ O), 72.5 (OCH ₂ (CH ₂ ) ₁₀ ); HR ESI MS m/z calc for C ₃₅ H ₇₀ NaO ₁₀ S ₂ (M-Na) 737.4303, found 737.4256. Example 24D

Disodium 4,8-dioxa-6,6-bis(tetradecyloxymethyl)-1,11-undecanedisulfon ate

H ₃ C(H ₂ C) ₁₃ O 0(CH ₂ )I ₃ CH ₃

24d

Compound 24d is made following the procedure of Example 24B from 1 ,3- propanesultone (2 ml_, 21 mmol, 10 eq) in THF (5 ml_), compound 2d (Example 2D) (1.13 g, 2.14 mmol) in dry THF (5 ml.) using two identical additions of suspensions of 60% oil dispersions of sodium hydride (0.2 g, 4.3 mmol, 2.25 eq), each followed by stirring for 12 h at 40 ⁰ C, then a third addition (0.1 g, 2.4 mmol, 1.13 eq) followed by stirring at 35°C for 24 h and then for 12 h at rt. Normal work up gives a white solid that is purified by column chromatography as for Example 24A followed by crystallization from ethyl acetate / methanol to give an amorphous colorless solid: yield 1.43 g, 82%; mp 175-180°C, becomes transparent, 210-245 ⁰ C decomposes; R _F 0.44 (butanol water methanol: 10 2.5 1.5); ¹ H NMR (500.13 MHz, methanol-cf ₄ ) δ 0.89 (t, J = 6.8 Hz, 6H, 2 x CH ₃ ), 1.28-1.31 (br s, 44H, 22 x CH ₂ ), 1.54 ( pentet, J = 6.5 Hz, 4H, 2 x OCH ₂ CH ₂ (CH ₂ ) _I i); 2.05 (m, 4H, 2 x O ₃ SCH ₂ CH ₂ ), 2.91 (m, 4H, 2 x ^" O ₃ SCH ₂ ), 3.36 (s, 4H, 2 x (CH ₂ ) _I3 OCH ₂ C), 3.377 (t, 4H, J = 6.3 Hz, 2 x OCH ₂ (CH ₂ ) ₁₃ ), 3.382 (s, 4H, 2 x O ₃ S(CH ₂ ) ₃ OCH ₂ C), 3.48 (t, 4H, J = 6.1 Hz, 2 x O ₃ S(CHz) ₂ CH ₂ O); ¹³ C NMR (125.77 MHz, D ₂ O) δ 13.9 (2 x CH ₃ ), 22.8 (2 x CH ₂ CH ₃ ), 24.7 (2 x O ₃ SCH ₂ CH ₂ ), 26.4 (2 x OCH ₂ CH ₂ CH ₂ ), 29.7-30.1 (2 x OCH ₂ CH ₂ and alkyl chain carbons), 32.1 (2 x CH ₂ CH ₂ CH ₃ ), 45.3 (q C), 48.3 (2 X O ₃ SCH ₂ ), 69.2 (2 x CH ₂ O(CH ₂ )i ₃ ), 69.6 (2 x

O ₃ S(CH ₂ ) ₃ OCH ₂ ), 70.1 (2 x O ₃ S(CH ₂ ) ₂ CH ₂ O), 71.5 (OCH ₂ (CH ₂ ) ₁₂ ); HR ESI MS m/z calc for C ₃₉ H ₇₈ NaO ₁₀ S ₂ (M-Na) 793.4929, found 793.4929.

Example 25

Physicochemical Properties of Gemini Surfactants [00234] Equilibrium surface tension measurements (γ values) are performed using the Wilhelmy plate technique. Measurements of surface tension are performed with either a KRUSS K8 manual or K10 digital tensiometer; the accuracy is ± 0.1 mN-m ^"1 . All measurements are done in a jacketed beaker at 20.0 ⁰ C, using either a Haake or Neslab refrigerated bath (± 0.2 ⁰ C). In general, 10-15 concentration points for each surfactant/water system are obtained. The results from either duplicate or triplicate trials are averaged to obtain the surface tension (γ) versus log of the total surfactant concentration (C _surf]t ) profiles. Figure 2 shows a plot of surface tension (mN nn ^'1 ) versus log ₁₀ of the total surfactant concentration (molar) for compounds 5a-5d (Examples 5A- 5D) and Figure 3 is a plot of surface tension (mN m ¹ ) versus log ₁₀ of the total surfactant concentration (molar) for compounds 22c-22f (Examples 22C-22F).

[00235] Critical micelle concentration (CMC) is determined by a linear regression analysis of both the pre and post-micellar lines of each surface tension plot to identify the intersection point. (Dreger, E. E.; Keim, G. I.; Miles, G. D.; Shedlovsky, L.; Ross, J. Ind.

Eng. Chem. 1944, 36, 610-617; Boucher, E. A.; Grinchuk, T. M.; Zettlemo, A. C. J.

Colloid. Interface Sci. 1967, 23, 600-603). The surface excess concentration (T) of a surfactant can be approximated as the actual surface concentration without introducing considerable error (Song, LD.; Rosen, M.J. Langmuir 1996, 12, 1149-1153). The surfactant concentration at the interface is calculated from the surface tension data using the Gibbs equation:

The differential term in the Gibbs equation is obtained from the slope of a plot of γ (surface tension) versus the natural logarithm of surfactant concentration at constant temperature. For dimeric surfactants, n=3. When γ is in mN m ^"1 and R = 8.314 J mol ^"1 K ^"1 , r will have units of mol/1000 m ² .

[00236] The area of one monomer (A _mm ) at the interface can be determined from the surface excess using the following equation (Rosen, M. J. Chemtech 1993, 23, 30-33; Boucher, E. A.; Grinchuk, T. M.; Zettlemo, A. C. J. Colloid. Interface Sci. 1967, 23, 600- 603; Song, L. D.; Rosen, M. J. Langmuir 1996, 12, 1149-1153; Rosen, M. J.; Song, L. D. J. Colloid. Interface Sci. 1996, 179, 261-268):

A . = ' r ^x

[00237] where N _Av0 = Avogadro's number and r is in mol/m ² . The CMC values are substituted into the linear regression equation of the pre-micellar line to determine the surface tension at the CMC. The surfactant concentration which lowers the surface tension by 20 mN/m (C ₂₀ ) is determined by substituting 52 mN m ^"1 into the linear regression equation for the pre-micellar line and solving for the appropriate concentration. The CMC values for compounds 5a to 5d (Examples 5A to 5D) are given in Table 1. Table 1 - CMC and surface tension derived quantities for compounds 5a-5d (Examples 5A-5D).

Chain CMC

Compound YCMC "mm Length pC ₂ o (10 ^"3 ItIoI L ^"1 ) (mN/M) (nm ² )

5a 8 1.19 3.59 31.9 1.53

5b 10 0.165 4.70 32.2 1.61

5c 12 0.00159 5.92 33.1 0.355

5d 14 0.000565 6.41 32.6 0.302

[00238] From the results in Table 1 , it can be seen that, in at least one embodiment, the CMC values of the compounds of formula I decrease as the alkyl chain length increases. A corresponding trend in C ₂ o values is seen. The area/monomer at the interface is relatively large, consistent with the presence of the two cationic head groups at the interface.

[00239] A comparison of CMC values for some surfactants of the present invention with other conventional and known gemini surfactants is given in Table 2. Table 2 - Comparison of CMC and surface tension quantities for some compounds of formula I and common conventional and dimeric surfactants

¹ Menger, F. M.; Keiper, J. S. Gemini Surfactants. Angewandte Chemie International

Edition 2000, 39, 1906-1920.

² Alami, E.; Levy, H.; Zana, R. Alkanediyl-α,ω-Bis(Dimethylalkylammonium Bromide)

Surfactants. 2. Structure of the Lyotropic Mesophases in the Presence of Water. Langmuir 1993, 9, 940-949.

[00240] It can be seen from Table 2 that, in at least one embodiment, the CMC values of the compounds of formula I are lower than that of single-headed, single-tailed and two-headed surfactants of various types. Furthermore, for at least one cationic series of the compounds of formula I, the CMC value increases with an increase in the number of CH ₂ groups in the methylene spacer, reaching a maximum with four methylene chains and decreasing thereafter. In addition, in at least one embodiment, CMC values appear to be the smallest when the spacer group is a short, slightly hydrophilic chain or a flexible hydrophobic chain.

[00241] In the following Tables 3 to 6, physicochemical properties of the surfactants of the present invention are compared against those of known monomeric and dimeric surfactants. Comparative monomeric surfactants, denoted n-TAB, where n is the number of carbon atoms in the C _n H _2n+I alkyl chain, have the following chemical structure (Menger, F. M.; Keiper, J. S. Gemini Surfactants. Angewandte Chemie International Edition 2000, 39, 1906-1920):

/ ^CH 3

C _n H ₂ π+1 \ CH ₃ Br CH ₃

Comparative dimeric surfactants, denoted n-5-n, where n is the number of carbon atoms in the C _n H _2n+1 alkyl chain, have the following chemical structure (Alami, E.; Levy, H.; Zana, R. Alkanediyl-α,ω-Bis(Dimethylalkylammonium Bromide) Surfactants. 2. Structure of the Lyotropic Mesophases in the Presence of Water. Langmuir 1993, 9, 940-949):

[00242] The CMC results of the compounds of formula (I) as well as comparative monomeric and dimeric surfactants are compared in the following table.

Table 3 - CMC comparisons for the compounds of formula I with comparator compounds

Comparative Comparative

Chain monomeric dimeric Compounds of

Length surfactants surfactants formula I

(n) (n-TAB) (n-5-n) (Examples 5b-5d)(M)

(M) (M)

10 6.2 x 10 ^"2 1.7 x 10 ^"2 1.7 x 10 ^"4 12 1.4 x 10 ^~2 1.2 x 10- ³ 1.6 x 10 ^"6 14 3.6 x 10 ³ 1.1 X 10 ^"4 5.7 x 10- ⁷

[00243] The n-5-n dimeric surfactants are known to have CMC values that are commonly lower than those of their analogous monomeric surfactants (Rosen, M.J.; Tracy, DJ. J. Surfact. Det. 1998, 1, 547-554); this is observed here. The results in Table 3 indicate that in at least one embodiment, compounds of formula I can form micelles at a lower concentration than either the n-5-n or n-TAB compounds. This result indicates that in at least one embodiment, surfactants of the present invention could be used in concentrations appreciably smaller than those of conventional dimeric surfactants while continuing to provide their maximum surface tension lowering effect.

Table 4 - Comparison of pC ₂ o for the compounds of formula I with comparator compounds.

Chain Comparative Comparative dimeric Compounds of

Length monomeric surfactants surfactants formula I

(n) (n-TAB) (n-5-n) (Examples 5b-5c)

10 2.1 4.0 4.7 12 2.8 4.9 5.9

[00244] From these results, it can be seen that the C ₂ o value decreases going from the monomeric n-TAB surfactants to the dimeric n-5-n surfactants; the results for surfactants of the present invention show a further decrease. These results support the low concentration of at least one embodiment of the compounds of formula I necessary to have a large effect on the surface tension. Table 5 - Comparison of γc _M c values for the compounds of formula I with comparator compounds.

Chain Comparative Comparative dimeric Compounds of

Length monomeric surfactants surfactants formula I

(n) (n-TAB) (n-5-n) (Examples 5c-5d)

12 39 40 32 14 38 39 33

[00245] The results in Table 5 show that, in at least one embodiment, the γ _CM c values for the compounds of formula I are lower than those of the comparator compounds.

Table 6 - Comparison of A _m , _π at the air water interface for the compounds of formula I with comparator compounds

Chain Comparative Comparative dimeric Compounds of

Length monomeric surfactants surfactants formula I

(n) (n-TAB) (n-5-n) (Examples 5b-5d)

10 1.24 12 0.49 1.70 0.34 14 0.61 1.56 0.29

[00246] The results shown in Table 6 show that, in at least one embodiment, the A _mιn for the compounds of formula I can be slightly lower than that for the monomeric surfactants.

[00247] One of the main reasons for the extensive use of surfactants in commercial and industrial applications is to reduce the surface tension of water or the interfacial tension of a hydrocarbon/water interface, for example. Two key parameters related to the equilibrium surface tension lowering ability of surfactants are the C ₂₀ value (the concentration of surfactant required to lower the surface tension of the solvent by 20 dynes/cm) and the surface tension at the CMC (the γ _CM c value). It is clear from the data in Tables 4 and 5 that for at least one embodiment of the surfactants of the present invention listed, the C ₂ o values are lower than those of comparable monomeric and dimeric surfactants. Furthermore, the γ _CM c values of at least one embodiment of the surfactants of the present invention are comparable to or lower than those of comparator compounds.

[00248] Because of these properties, it is envisioned that in at least one embodiment, the compounds of formula I can be more cost-effective than are conventional surfactants. For example, in at least one embodiment, the compounds of formula I can act to reduce surface tension and/or can form micelles at concentrations lower than those required of conventional surfactants. In addition, in at least one embodiment, the compounds of formula I can have C ₂₀ values (the concentration of surfactant required to lower the surface tension by 20 dynes/cm) lower than those of conventional surfactants. Thus, in at least one embodiment, the amount of the compounds of formula I required can be substantially reduced compared to the amount of conventional surfactants required for the same application. Furthermore, in at least one embodiment, the compounds of formula I can be easy to dispose of, potentially providing further cost savings.

[00249] The previous detailed description is provided to enable any person skilled in the art to make or use the present invention. Various modifications to those embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention described herein. Thus, the present invention is not intended to be limited to the embodiments shown herein, but is to be accorded the full scope consistent with the claims, wherein reference to an element in the singular, such as by use of the article "a" or "an" is not intended to mean "one and only one" unless specifically so stated, but rather "one or more". All structural and functional equivalents to the elements of the various embodiments described throughout the disclosure that are known or later come to be known to those of ordinary skill in the art are intended to be encompassed by the elements of the claims. Moreover, nothing disclosed herein is intended to be dedicated to the public regardless of whether such disclosure is explicitly recited in the claims.