TRANSFORMATION OF PEROXYACETAL INTERMEDIATE

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional application serial number 61/904,679, filed November 15, 2013; and U.S. Provisional application serial number 61/979,306, filed April 14, 2014, the disclosures of which are specifically incoiporated herein by reference in their entireties.

FIELD OF THE INVENTION

[0002] The disclosures herein relate to processes for transforming a compound of formula Ila:

, wherein A is a C ₆ -Ci alkene chain with at least one double bond, R ¹ is a Q-C _t o alkyl, and R ³ is an oxygen-containing functional group.

BACKGROUND OF THE INVENTION

[0003] The transformation of an aldehyde-alkoxy hydroperoxide intermediate to an ester has been reported by Schreiber, et al, (S.L. Schreiber, R.E. Claus, and J. Reagen, Tetrahedron Lett, 23, 3867 (1982)) ("Schreiber"). Ozonolysis of a mono-unsaturated cycloalkene is carried out at a temperature of -78°C to form an aldehyde-alkoxy hydroperoxide intermediate. In Schreiber, acetic anhydride and triethylamine are used in the dehydration step of the aldehyde-alkoxy hydroperoxide intermediate.

[0004] In Schreiber, a one-pot sequence was employed to complete the transformation. It has been recognized that when alcohols are used, the one-pot synthesis produces complex azeotropes of alkyl acetate, alcohol and acid. The separation of these azeotropes becomes very difficult if one wants to recover the recyclable components for cost benefits. The required separation steps are practically cost-prohibitive due to the poor component yields and significant distillative equipment costs. Thus, there is a need in the field to eliminate these azeotropic complexes and to simplify the subsequent process. [0005] In Gorezynski et al, Journal of Medicinal Chemistry, 52, 4631-4639, 2009 ("Gorezynski"), methyl 12-oxododecanoate is prepared from cyclododecene ozonolysis at -78°C in the presence of anhydrous Na ₂ C0 ₃ in CH2CI ₂ and methanol.

[0006] One disadvantage of the Gorezynski preparation is the use of caustics, chlorides and benzene components. The product recovery is very complex, requires multiple steps and would generate waste streams that are difficult to dispose.

SUMMARY OF THE INVENTION

[0007] The disclosed process addresses the practical problem of handling azeotropic complexes that are formed due to the generally unstable intermediate. More specifically, the disclosed process provides an improved synthesis process wherein a thermally stable intermediate is formed, which allows the excess reagent, e.g., an alcohol, to be removed. Also, the excess reagent removal prior to the transformation step does not require an additional solvent extraction step as disclosed in other references. See, e.g., U.S. Patent No. 3,059,058. The disclosed process provides a practical and economic process sequence to recover the excess reagents and useful byproducts while preserving the intermediate integrity for the downstream processing steps.

[0008] One aspect of the disclosed process is directed to a method for transforming a

compound of formula Ila: to a compound of formula III: , wherein A is a Ο ₆ -Ο ₁₀ alkene chain with at least one double bond, R ¹ is a C1-C10 alkyl, and R ³ is an oxygen-containing functional group, without forming an acetate side product.

[0009] Another aspect of the disclosed process is directed to a method of making a compound

of formula III: comprising: a. contacting a compound of formula I: a reagent with a medium

comprising ozone to form a compound of formula Ila: ; and b. allowing the compound of formula Ila transform to the compound of formula III, without forming an acetate side product;

wherein A ₅ R 1' _? and R 3 ^J are defined as described above.

[0010] Another aspect of the disclosed process is directed to a method of making R ⁴ -A-R ⁴ comprising:

a) contacting a compound of formula I: and a carboxylic acid with a medium comprising ozone, and

b) forming an ozonolysis product; wherein the resulting ozonolysis product is not isolated, and

c) allowing the ozonolysis product to transform to R ⁴ -A-R ⁴ ;

wherein, A is a C ₆ -Cio alkene chain with at least one double bond; and R ⁴ is an aldehyde group.

[0011] Another aspect of the disclosed process is directed to a composition comprising a

compound of formula II: _} wherein A is a Q- o alkene chain with at least one double bond; R is a Ci-C ₁₀ alkyl; R is H, acetyl,; and R is an oxygen-containing functional group.

[0012] Another aspect of the disclosed process is directed to a composition comprising a

compound of formula III: , wherein A is a C ₆ -Cio alkene chain with at least one double bond, R is a C^Cio alkyl, and R is an oxygen-containing functional group. [0013] Another aspect of the disclosed rocess is directed to a method for transformin a

compound of formula Ila': to a compound of formula IV:

wherein B is a C ₆ -Cio alkylene chain, R ¹ is a Ci-C ₁₀ alkyl, and R ³ is an oxygen-containing functional group, without forming an acetate side product.

[0014] Another aspect of the disclosed process is directed to a method of making a compound

of formula Ila' : _; comprising:

contacting a compound of fozrnula Γ: , and a reagent with a medium comprising ozone; forming a reaction mixture comprising the compound of formula Ila', and without isolating the product from the ozone; and recovering the product comprising the compound of formula Ila'; wherein, B is a C ₆ -C ₁₀ alkylene group; R ¹ is a Ci-C^ alkyl; R ³ is an oxygen-containing functional group.

[0015] disclosed process is directed to a method of making a compound

of formul ¹ comprising: B

a. contacting a compound of formula Γ:o and a reagent with a medium

comprising ozone to form a compound of formula Ha': ; and b. allowing the compound of formula Ila' transform to the compound of formula IV, without forming an acetate side product;

wherein B, R , and R are defined as described above.

[0016] Another aspect of the disclosed process is directed to a method of making R ⁴ -B-R' comprising: a) contacting a compound of formula carboxylic acid with a medium comprising ozone, and

b) forming an ozonolysis product; wherein the resulting ozonolysis product is not isolated, and

c) allowing the ozonolysis product to transform to R ⁴ -B-R ⁴ ;

wherein, B is a C6-C ₁₀ alkylene chain; and R ⁴ is an aldehyde group.

BRIEF DESCRIPTION OF THE DRAWING

[0017] FIG. 1 is a representation of a process involving removal of reagent prior to catalytic transformation of the compound of formula Ila by contacting with the catalytic complex in accordance with an embodiment of the disclosed process.

[0018] FIG. 2 is a representation of a molecular transformation according to one embodiment of the disclosed process.

[0019] FIG. 3 is a representation of the heat flow characteristics of the compounds according to Example 14, measured by single-cell, Differential Scanning Calorimetry (DSC).

[0020] FIG. 4 is a representation of the heat flow characteristics of the compounds according to Example 15, measured by single-cell DSC. [0021] FIG. 5 is a representation of a molecular transformation according to one embodiment of the disclosed process.

DETAILED DESCRIPTION OF THE INVENTION

[0022] Embodiments of the invention described and claimed herein are not to be limited in scope by the specific embodiments herein disclosed, since these embodiments are intended as illustration of several aspects of the disclosure. Any equivalent embodiments are intended to be within the scope of this disclosure. Indeed, various modifications of the embodiments in addition to those shown and described herein will become apparent to those skilled in the ait from the foregoing description. Such modifications are also intended to fall within the scope of the appended claims.

[0023] The invention has been described broadly and generically herein. Each of the narrower species and subgeneric groupings falling within the generic disclosure also form part of the invention. This includes the generic description of the invention with a proviso or negative limitation removing any subject matter from the genus, regardless of whether or not the excised material is specifically recited herein. In addition, where featui'es or aspects of the invention are described in terms of Markush groups, those skilled in the art will recognize that the invention is also thereby described in terms of any individual member or subgroup of members of the Markush group.

[0024] As used herein and in the appended claims, the singular forms "a," "an," and "the" include plural reference unless the context clearly dictates otherwise. Thus, for example, a reference to "a reactor" includes a plurality of reactors, such as in a series of reactors. In this document, the term "or" is used to refer to a nonexclusive or, such that "A or B" includes "A but not B," "B but not A," and "A and B," unless otherwise indicated.

[0025] Values expressed in a range format should be interpreted in a flexible manner to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. For example, a range of "about 0.1% to about 5%" or "about 0.1 % to 5%" should be interpreted to include not just about 0.1% to about 5%, but also the individual values (e.g., 1%, 2%, 3%, and 4%) and the sub-ranges (e.g., 0.1% to 0.5%, 1.1% to 2.2%, 3.3% to 4.4%) within the indicated range. The statement "about X to Y" has the same meaning as "about X to about Y," unless indicated otherwise. Likewise, the statement "about X, Y, or about Z" has the same meaning as "about X, about Y, or about Z," unless indicated otherwise.

[0026] In the methods described herein, the steps can be carried out in any order without departing from the principles of the invention, except when a temporal or operational sequence is explicitly recited. Furthermore, specified steps can be earned out concurrently unless explicit claim language recites that they be carried out separately. For example, a claimed step of doing X and a claimed step of doing Y can be conducted simultaneously within a single operation, and the resulting process will fall within the literal scope of the claimed process.

[0027] The term "about" as used herein can allow for a degree of variability in a value or range, for example, within 10%, within 5%, or within 1% of a stated value or of a stated limit of a range.

[0028] The term "substantially" as used herein refers to a majority of, or mostly, as in at least about 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, 99.99%, or at least about 99.999% or more.

[0029] The term "alkene" as used herein refers to a linear or branched hydrocarbon olefin that has at least one carbon-carbon double bond.

[0030] The term "alkyl" or "alkylene" as used herein refers to a saturated hydrocarbon group which can be an acyclic or a cyclic group, and/or can be linear or branched unless otherwise specified.

[0031] The term "reagent" as used herein means a consumable material that provides the suitable R ¹ functionality in the compound of formula Ila or Ha'. In some embodiments, the reagent is polar. In other embodiments, the reagent provides a single continuous phase of the reaction. In yet another embodiment, the reagent improves the flowability characteristics of the reaction medium. [0032] The term "agent" as used herein means a consumable material that allows the ozonolysis product to transform to R ⁴ -A-R ⁴ or to R ⁴ -B-R ⁴ . In some embodiments, the agent is polar. In other embodiments, the agent provides a single continuous phase of the reaction. In another embodiment, the agent may provide a multi-phase reaction medium. In yet another embodiment, the agent improves the flowability characteristics of the reaction medium. In some embodiments, the agent improves the heat transfer properties of the reaction medium.

[0033] The term "ozonolysis product" is meant to include those structures, transient or otherwise susceptible to isolation if desired, resulting from the reaction of one ozone molecule with a single double bond of the compound of formula I. However, the applicants do not wish to be limited by or subject to any particular mechanistic interpretation as to the formation of an ozonolysis product.

[0034] The phrase "allowing the ozonolysis product to transform" is meant to include any changes to the reaction parameters (e.g., temperature) or addition of further reagents (e.g., a nucleophile) such that the ozonolysis product transforms to an acyclic alkene having terminal oxygenated functional groups and one fewer unsaturation.

[0035] All publications, including non-patent literature (e.g., scientific journal articles), patent application publications, and patents mentioned in this specification are incorporated by reference as if each were specifically and individually indicated to be incorporated by reference.

[0036] It is understood that the descriptions herein are intended to be illustrative, and not restrictive. Many other embodiments will be apparent to those of skill in the art upon reviewing the above description. The scope of the invention should, therefore, be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled. In the appended claims, the terms "including" and "in which" are used as the plain- English equivalents of the respective terms "comprising" and "wherein," respectively. Moreover, the terms "first," "second," "third," and the like are used merely as labels, and are not intended to impose numerical requirements on their objects.

[0037] In an embodiment, conversion of the compound of formula I is defined as a percent as follows: Number of grams of Number of grams of

the compound of formula Ϊ present prior to the compound of formula I present after

Ozonolysis Catalytic Transformation

Number of grams of

the compound of formula I present p

Ozonolysis

X 100

[0038] in an embodiment, conversion of the compound of formula I' is defined as a percent as follows

x 100

[0039] In an embodiment, a selectivity for the compound of formula III defined as a percent as

follows: (Number of moles of the compound of formula III) / (Number of moles of the

compound of formula I converted) x 100.

[0040] In an embodiment, a selectivity for the compound of formula IV defmed as a percent

as follows: (Number of moles of the compound of foniiula IV) / (Number of moles of the

compound of formula Γ converted) x 100.

[0041] One aspect of the disclosed process is directed to a method for transforming a

compound of formula Ila: ,

wherein A is a Ce-Qo alkene chain with at least one double bond, R ¹ is a Ci-Cio alkyl, and R ³ is

an oxygen-containing functional group, without forming an acetate side product.

[0042] In some embodiments, R is a C]-C ₆ alkyl. In another embodiment, R is a C2-C4

alkyl. In a further embodiment, R ¹ is propyl or butyl. [0043] In some embodiments, A is a C ₆ or o alkene chain with at least one double bond. In one embodiment, A is a C ₁₀ alkene with two double bonds. In another embodiment, A is a C ₆ alkene with one double bond.

[0044] In some embodiments, R ³ is an aldehyde, an acid, or an ester group. In a further embodiment, R ³ is an aldehyde or an acid group. In another further embodiment, R ³ is an aldehyde group.

[0045] In one embodiment, the transformation is in the presence of an acid anhydride. Examples of suitable anhydrides include, but are not limited to, acetic anhydride, succinic anhydride, maleic anhydride, other anhydrides belonging to the general anhydride family and mixtures thereof. Acetic anhydride is preferred.

[0046] In some embodiment, the transformation is in the presence of a catalyst. In other embodiments, the catalyst is homogenous. In a further embodiment, the catalyst is a mixture of acid and amine. In another embodiment, the amine and the acid can be freshly mixed, premixed, azeotropically co-distilled, or recycled.

[0047] Examples of suitable acids include, but are not limited to, acetic acid, succinic acid, maleic acid. In a further embodiment, the acid is acetic acid.

[0048] In some embodiments, the amine is compatible with the acid and suitable for driving base-catalyzed reactions.

[0049] In some embodiments, the amine may be a hindered secondary amine. In other embodiments, the amine may be a tertiary amine. In some other embodiments, the amine may be a cyclic amine.

[0050] In some embodiments, the amine may be represented by a quaternary ammonium cation; commonly known as the "quaternary amines". In quaternary amines, there are four organic substituents, such as alkyl, aryl or both, attached to the charged nitrogen center. Examples may include quaternary ammonium salts with a variety of anions.

[0051] In some embodiments, the amine may be represented by a biogenic substance with one or more amine groups; commonly known as the "biogenic amines". Biogenic amines are nitrogenous organic bases and are synthesized by microbial, enzymatic, vegetable and animal metabolism routes.

[0052] The tertiary amines are those in which all three hydrogen atoms are replaced by organic substituents, such as alkyl, aryl or both. Examples of tertiary amines include, but are not limited to, trialkyl amines such as trimethy-, triethyl-, tripropyl-, tributyl-amine, and aromatic tertiary amines such as triphenylamine.

[0053] Examples of suitable amines include, but are not limited to, triethyl amine, diethanol amine, tributyl amine, pyridine, other unsubstituted or substituted amines belonging to the general amines family and mixtures thereof. Triethyl amine is preferred.

[0054] In some embodiments, the molar ratio of acid and amine may range from about 1 : 100 to about 100:1. In one embodiment, the molar ratio of acid and amine may range from about 1 :25 to about 25: 1. In another embodiment, the molar ratio of acid and amine may range from about 1 : 10 to about 10:1. h a further embodiment, the molar ratio of acid and amine may range from about 1 :6 to about 6:1. In yet another embodiment, the molar ratio of acid and amine is about 1 : 1.

[0055] In some embodiments, the necessity of using acetic anhydride and triethyl amine in the transformation reaction may be removed by replacing with either a homogeneous or heterogeneous catalytic system. In one aspect, the catalytic systems have nucleophilic / basic characteristics. These properties may be comprised into one system or be discrete entities and admixed.

[0056] In some embodiments, molecular sieves, zeolites, mesoporous and microporous materials may be comprised into the catalytic systems. In other embodiments, mesoporous systems such as MCM-41, MCM-48, and SBA-15 may be comprised into the catalytic systems. In one embodiment, Zeolites X and L may be comprised into the catalytic systems. In another embodiment, ion-exchange of the solid materials with alkali metals such as K, b ₅ and Cs may be conducted. In yet another embodiment, the solid materials may be functionalized with amines via grafting and intercalation. In one aspect, basic nucleophiles may be incorporated into the frame work of the material. [0057] In some embodiments, the catalyst can be basic zeolites, mesoporous materials, microporous materials, materials with both mesoporous and microporous characteristics, and combinations thereof.

[0058] In some embodiments, the catalyst(s) and mixtures thereof are promoted and/or are comprised of functional groups, e.g. an amine. In other embodiments, the catalyst functional groups are basic and include lone pair electrons on heteroatoms including O, N, P, B and S.

[0Θ59] In some embodiments, a drying agent may be physically mixed with the catalyst. In other embodiments, the drying agent may be comprised of silica gel and/or molecular sieves, especially, 4 A and 5 A.

[0060] In one embodiment, the transformation is in the presence of a mixture of an acid and a base. In one embodiment, the base can be an inorganic base. Examples of the suitable inorganic base include, but are not limited to, KOH, K3PO4, KF, CsF, NaOAc and KOAc.

[0061] In some embodiments, the compound of formula Ila first transforms to a compound of

formula lib: before the compound of formula III is formed, wherein R is an acetyl group.

[0062] In some embodiments, the transformation is conducted under substantially solvent free condition. In a further embodiment, the transformation is in the absence of a solvent. In other embodiments, the transformation is in the presence of an inert solvent. Examples of the suitable inert solvent include, but are not limited to, Ci-C ₆ alkyl acetates, Ci-C ₆ alcohols, ethers, acetic acid, succinic acid, maleic acid, dimethyl formamide (DMF), dimethyl acetamide (DMAc), dimethyl sulfoxide (DMSO), n-methyl pyrrolidinone (NMP), tetrahydrofuran (THF), and mixtures thereof. 0063] In one embodiment, the transformation is in the presence of a compound of formula I:

, wherein A is a C ₆ -C ₁₀ alkene chain with at least one double bond. [0064] Another aspect of the disclosed process is directed to a method of making a compound

of formula III: comprising:

a. contacting a compound of formula I: and a reagent with a medium

comprising ozone to form a compound of formula Ila: ; and b. allowing the compound of formula Ila transform to the compound of formula III, without forming an acetate side product;

wherein A, ¹ , and R ³ are defined as described above.

[0065] In one embodiment, the reagent is provided in excess. In this context, the term "excess" is defined as the molar amount of the reagent is more than the reacted compound of formula I. In some embodiments, the method further comprising at least partially removing the excess reagent prior to b). In a further embodiment, majority of the excess reagent is removed prior to b). In some embodiments, the excess reagent is removed via flash distillation. In another embodiment, the catalyst is at least partially removed with the reagent. In a further embodiment, majority of the catalyst is removed. In some embodiments, the removed catalyst and/or reagent are recycled back to the process.

[0066] In some embodiments, the transformation is in the presence of a catalyst. Ozonolysis

[0067] The compound of formula Ila may be obtained by ozonolysis of the compound of formula I. International Application No. PCT/US2014/045808, filed July 8, 2014, (the '808 application) discloses a process for obtaining the compound of formula Ila from a selective ozonolysis of the compound of formula I. The entire contents and disclosure of the '808 application are incorporated herein by reference. [0068] The compound of formula I may include cyclic trienes and cyclic dienes. Examples of the compound of formula I include, but are not limited to, cyclohexadiene, cycloheptadiene, cyclooctadiene, cyclooctatetraene, cyclododecadiene, cyclododectriene, cyclododecapentaene including isomers and mixtures thereof. In some embodiments, the compound of formula I is cyclododecatriene or cyclooctadiene. In a further embodiment, the compound of formula I is 1,5,9-cyclododectriene (CDDT) or 1,5-cyclooctadiene (COD). In another further embodiment, the compound of formula I is CDDT.

[0069] In some embodiments, the compound of formula I has a purity of at least 90%. In other embodiments, the compound of formula I has a purity of at least 95%. In a further embodiment, the compound of formula I has a purity of at least 98%. In another further embodiment, the compound of formula I has a purity of at least 99%.

[0070] In some embodiments, the reagent is a -Qo alcohol. Examples of the suitable alcohol include, but are not limited to, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2- butanol, iso-butanol, t-butanol, and mixtures thereof. In some embodiments, the alcohol is 1- propanol, 2-propanol, 1 -butanol, 2-butanol, iso-butanol, /-butanoi, and mixtures thereof. In other embodiments, the reagent is a C ₄ -C ₁₀ alcohol. Higher alcohols such as butanols, etc., are preferred.

[0071] In some embodiments, the reagent is anhydrous, preferably contains less than 0.5 wt.% water, or more preferably less than 0.1 wt.% water. In other embodiments, the water content may be no more than 0.08 wt%, preferably no more than 0.04 wt%.

[0072] In some embodiments, the amount of the reagent may vary and generally excess reagent may be used. For puiposes of the disclosed process, the molar ratio of the compound of formula I to the reagent may be about 100:1 to about 1 :100, preferably about 25:1 to about 1 :25, and more preferably about 10:1 to about 1:10. In one embodiment, the molar ratio of the compound of formula I to the reagent is about 4:1 to about 1 :10. In another embodiment, the molar ratio of the compound of formula I to the reagent is about 6:1 to about 1 :6. In yet another embodiment, the molar ratio of the compound of formula I to the reagent is about 3:1 to about 1:3. [0073] In some embodiments, the concentration of the compound of formula I in the reaction zone, by weight, may be about 0.1% to 99.9% range. In one embodiment, the compound of formula I is present in the about 0.5%-25% concentration range. In other embodiments, the compound of formula I is present in the about 25%-35%, in the about 35%-45%, in the about 45%-55%, in the about 55%-65%, in the about 65%-75%, in the about 75%-85%, in the about 85%-95%, or in the about 95-99.9% concentration range. The compound of formula I concentration range may be from about 25% to about 85%, preferably from about 30% to about 75%, and more preferably from about 30% to about 65%. In one embodiment, the compound of formula I is from about 35% to about 60% by weight.

[0074] In some embodiments, the ozonolysis reaction may be conducted in the presence of an optional inert solvent. In other embodiments, the inert solvent is a polar solvent. Examples of the suitable polar solvent include, but are not limited to, Ci-Cf, alkyl acetates, ethers, DMF, DMAc, DMSO, NMP, THF, and mixtures thereof.

[0075] The ozone-containing gas may comprise a mixture of ozone and at least one carrier gas. The amount of ozone may vary. In some embodiments, ozone may be from about 0.01 mol.% to about 100 mol.%. In a further embodiment, ozone may be from about 0.1 mol.% to about 10 mol.%), from about 10 mol.% to about 30 mole.%, from about 30 mol.% to about 50 mole.%, from about 50 mol.%! to about 70 mole.%, from about 70 mol.% to about 90 mole.%>, or from about 90 mol.% to about 100 mole.%. In other embodiments, ozone may be from about 0.1 mol.% to about 25 mol.%. In a further embodiment, ozone may be from about 1 mol.% to about 20 mol.%. In another further embodiment, ozone may be from about 1 mol.% to about 15 mol.%.

[0076] The carrier gas may be selected from the group consisting of nitrogen, argon, carbon dioxide, oxygen, air, and mixtures thereof. In one aspect, the ozone-containing gas may comprise ozone, oxygen, and argon, h one embodiment, the ozone-containing gas may comprise ozone, oxygen, and nitrogen. In another embodiment, the ozone- containing gas may comprise ozone and carbon dioxide. There is no restriction on which earlier is to be used so long as it is chemically compatible with ozone and the carrier itself does not lead to undesirable reactions with the hydrocarbon substrate, [0077] In some embodiments, the ozone may be introduced in the dissolved state using an appropriate solvent. In other embodiments, the concentration of ozone may be enriched by injecting ozone into a pressurized circulation loop.

[0078] In some embodiments, the concentration of ozone in the ozone-containing medium, by weight, may be from about 0.01% to about 100%. In other embodiments, the ozone concentration may be from about 0.5% to about 5%, from about 5% to about 25%, from about 25% to about 50%, from about 50% to about 75%, from about 75% to about 100%.

[0079] In some embodiments, the total addition of ozone is at least partially influenced by the desired conversion and efficiency of ozone take-up. The ozone-containing gas is passed through the reaction solution for a period of time sufficient to permit selective cleavage of only one double bond. In some embodiments, the period of time may range from about 10 minutes to about 300 minutes. In a further embodiment, the period of time may range from about 30 minutes to about 200 minutes. The total ozone fed to the process can be either sub- stoichiometric, stoichiometric or excess with respect to the one double bond in the compound of formula I that is converted. In one example, the total moles of ozone fed to the process are in the stoichiometric ratio with respect to the moles of one double bond in the compound of formula I that is converted.

[0080] The flow rate of ozone fed may depend on the scale of operation and the desired conversion within the reaction time chosen. In some embodiments, the ozone flow rate is in the range from about 0.001 g/min to about 1 g/min. In a further embodiment, the ozone flow rate is in the about 0.005 g/min to about 0.8 g min range. In another further embodiment, the ozone flow rate is in the about 0.01 g/min to about 0.2 g/min range, In yet another further embodiment, the ozone flow rate is in the about 0.02 g/min to about 0.08 g/min range.

[0081] In some embodiments, the conversion of the compound of formula I is from about 0% to about 100%. In a further embodiment, the conversion of the compound of formula I is from about 10% to about 95%. In other further embodiments, the conversion of the compound of formula I is from about 20% to about 90%, from about 30% to about 70%, or from about 30% to about 60%. In other embodiments, the conversion of the compound of formula I is at least 20%. In a further embodiment, the conversion is at least 25%. [0082] As disclosed in the '808 application, the ozonolysis reaction can be conducted under conditions to selectively ozonize only one carbon-carbon double bond in the compound of formula I to form the compound of formula Ila. In a non-selective ozonolysis, more than one carbon-carbon double bonds are converted and non-selective products are formed. In some embodiments, the ozonolysis conditions favor the compound of formula Ila with the preservation of "A" as in the compound of formula I. For example, in the compound of formula Ila from the ozonolysis of CDDT, "A" should be a C ₁₀ alkene chain with two carbon-carbon double bonds. Due to the cleaving of more than one double bonds, in some embodiments, the non- selective products contain the compound of formula Ila with fewer carbon numbers in "A" than the compound of formula I,

[0083] In some embodiments, the ozonolysis effluent may comprise from about 0wt.% to about 50wt.% the compound of formula I, from about 0 wt.% to about 80 wt.% reagent, from about 0 wt.% to about 50 wt.% the compound of formula Ila, and up to about 15 wt.% nonselective products. The non-selective products may include compounds having two terminal oxygenated groups, which include dialdehydes, diacids, diesters, acid-esters, aldehyde-acids. In some embodiments, at least some of the non- selective products are saturated, for example, linear C ₄ species. In a preferred embodiment, the ozonolysis effluent comprises from about 0 wt.% to 50 wt.% of the compound of formula I, from about 0 wt.% to about 80 wt.% reagent, from about 0 wt.% to about 50 wt.% the compound of formula Ila, and up to about 10 wt.% non-selective products. In some embodiments, the ozonolysis effluent is a stable, flowable liquid at ambient conditions.

[0084] In some embodiments, the compound of formula Ila is formed with a selectivity of at least 50%. In other embodiments, the compound of formula Ila is formed with a selectivity of at least 60%. In another embodiment, the compound of formula Ila is formed with a selectivity of at least 70%. In other embodiments, the selectivity for the compound of formula Ila is at least 80%. In another embodiment, the selectivity for the compound of formula Ila is at least 85%. In a further embodiment, the selectivity for the compound of formula Ila is at least 90%. In another further embodiment, the selectivity for the compound of formula Ila is at least 95%. In some embodiments, the selectivity for the non-selective products is less than 10%. In a further embodiment, the selectivity for the non-selective products is less than 5%. [0085] In some embodiments, the ozonolysis reaction may be conducted at a temperature of less than 50°C, preferably from about -25°C to about 50°C, more preferably from about 0°C to about 40°C, and most preferably from about 0°C to about 25°C. The ozonolysis reaction is exothermic and, in some embodiments, the temperature of the reactor is maintained by a cooling system, such as an active jacketed cooler.

[0086] In some embodiments, the ozonolysis reaction may be conducted at a pressure from about 100 ton ^* to about 200 Psig. In other embodiments, the ozonolysis reaction may be conducted at a pressure from about 100 torr to about 100 Psig. In a further embodiment, the ozonolysis reaction may be conducted at a pressure from about 0 Psig to about 50 Psig, preferably from about 0 Psig to about 25 Psig, more preferably from about 0 Psig to about 20 Psig, and most preferably from about 0 Psig to about 10 Psig. In some embodiments, the vacuum operation may be most suitable for removing the reaction heat via evaporative cooling and so long as the reaction performance is not adversely impacted.

Thermal Stability

[0087] Schreiber discloses that "[t]he aldehyde-alkoxy hydroperoxides, 2, were often oligomeric and tended to be difficult to purify." The disclosed process has found that the compound of formula Ila has surprising and unexpected thermal stability. Advantageously, the unexpected thermal stability allows the effective removal of the excess reagent prior to the catalytic transformation step. Any presence of the excess reagent, e.g., an alcohol, may convert to its corresponding alkyl acetate during the catalytic transformation step. If the excess reagent, e.g., the alcohol, is not removed prior to the transformation step, the formation of alkyl acetate may lead to three major problems: 1) the recoverable reagent is depleted in the process; 2) the alcohol-acid equilibrium reaction adds 5-6 kcal/mole of exothermicity to the transformation step that must be managed; and 3) the formed alkyl acetate originates multiple binary and ternary azeotropic complexes downstream of the catalytic transformation process making the separation processes very complicated and almost cost-prohibitive. It is, therefore, the effective reagent removal prior to the catalytic transformation step is extremely beneficial to die downstream process and also assists in better management of the exothenriicity in the catalytic transformation step. Additional advantage of the excess reagent removal is that the recovered crude reagent may be effectively purified via conventional distillation and favorably recycled back to the ozonolysis reaction.

[0088] One desirable feature of the disclosed process is to remove the reagent prior to the catalytic transformation step, thus, little or no acetate side product is formed during the transformation step. Examples of the acetate side product, include, but are not limited to, alkyl acetate. Having produced a thermally stable product, e.g., the compound of formula Ila, the disclosed process principally affords a commercially advantageous step of the reagent removal without thermally degrading the mixture comprising the compound of formula Ila.

[0089] In some embodiments, the mixture comprising the compound of formula III is substantially free of the acetate side product. In one embodiment, the amount of the acetate side product is less than 2% wt. of the mixture comprising the compound of fomiula III. In another embodiment, the amount of the acetate side product is less than 1% wt. of the mixture comprising the compound of formula III.

[0090] Another aspect of the disclosed process is directed to a method of making a compound

of formula III: comprising:

a) contacting a compound of formula I: and a reagent with a medium comprising ozone to form a mixture comprising a compound of formula Ila: and the reagent;

b) exposing the mixture to a combination of temperature and pressure such that the reagent flashes to increase concentration of Formula Ila in the mixture without thermally degrading the compound of formula Ila component of the mixture; c) contacting the concentrated mixture comprising the compound of formula Ila with an acid anhydride and a trialkyl amine; and d) recovering a product comprising the compound of formula III;

wherein A is a C6-C ₁₀ alkene chain with at least one double bond, R ¹ is a Ci-C ₁₀ alkyl, and R ³ is an oxygen-containing functional group.

[0091] In some embodiments, as shown in FIG. 3, when the concentrated compound of formula Ila from CDDT was exposed to heat at 10°C/minute temperature ramp from 20°C to 220°C the material exhibited sufficient thermal stability up to about 60°C above which the DSC data indicated measurable heat flow and mass loss. Due to its thermal stability, the excess reagent may be distiJled off at about 50°C under reduced pressure without any measurable decomposition and thus no measurable yield loss. In an embodiment, the excess reagent may be removed at about 15°C to about 60°C temperature range and the pressure range of about 0 torr to about 100 torr. In another embodiment, the excess reagent may be removed at about 25°C to about 55°C temperature range and the pressure range of about 0.05 to about 30 ton-. The net impact is an improved overall process with a simpler backend separations scheme not having to deal with the azeotropes of alcohols, acetates and acids, the ability to cleanly recycle the catalyst, and recovery of the excess reagent in support of either continuous or batch processing without negative impact on the process. Thus, the ozonolysis products do not need to be separated and isolated from the ozonolysis effluent. This leads to further improved efficiencies in the process.

[0092] U.S. Patent No. 3,059,028 to Robert H. Perry (the Ό28 patent) teaches a process for the conversion of a cyclic triolefin via selective monoozonolysis to provide an olefinic monoozonolysis product. The process employs a cyclic non-conjugated polyolefin, a reactive ozonolysis solvent, an unreactive ozonolysis solvent, or a mixture thereof. At the end of the ozonolysis reaction, the reaction mixture is said to contain solvent, monoozonolysis product, and unreacted polyolefin. In Example I of the Ό28 patent, a method of recovering the monoozonolysis product from the reaction mixture includes room-temperature evaporation of the solvent mixture under a reduced pressure to provide two liquid phases. Further extraction with another solvent recovers the peroxidic monoozonolysis product assisted by excess methanol. The isolated peroxidic monoozonolysis product is obtained upon methanol evaporation under a reduced pressure. The disclosed process eliminates the multiple solvent extractions and the light- and heavy-phase separations, as taught in the '028 patent, hence makes the process more economically attractive. [0093J Also, in the Ό28 patent, the selectivity of monoozonolysis is preserved with very low conversions. For instance, in Example I, only 0.03 mol of ozone per mol of the triene was used, which resulted in a conversion of about 1/24 of the olefmic bonds in the triene to peroxide addition products of ozone and the triene. In contrast, when 0.6 or 1 mol of ozone per mol of the triene was used, the ozonolysis reaction is non-selective. (See Examples II and III of the Ό28 patent.)

[0094] In the disclosed process, the selectivity of monoozonolysis is preserved with much higher conversions. (E.g., see Examples 1-12 in Tables 2-4.)

[0095] In one embodiment, the compound of formula Ila is formed from ozonolysis of CDDT, wherein A is -CH ₂ -CH ₂ -CH=CH-CH ₂ -CH ₂ -CH=CH-CH ₂ -CH ₂ -. This compound of formula Ila is thermally stable.

[0096] Advantageously, the disclosed process does not require isolating the compound of formula Ila prior to the catalytic transformation step. Instead, the excess reagent and, optionally, a small portion of the compound of formula I are removed before the catalytic transformation step. The mixture containing the compound of formula Ila, the non-selective components, and the compound of formula I is passed along to the catalytic transformation step.

Catalytic Transformation

[0097] In some embodiments, after the excess reagent is removed, the enriched product stream is catalytically transformed in the presence of a catalyst to form the compound of formula III. In other embodiments, a homogeneous catalyst complex was used for the catalytic transformation reaction. In yet another embodiment, a heterogeneous catalyst may be used for the transformation reaction.

[0098] In some embodiments, the compound of formula lib is first formed from the reaction of the compound of formula Ila with an anhydride. The compound of formula lib is then contacted with the homogeneous catalytic complex generated "in- situ" from stoichiometrically liberated acid and added amine to be catalytically transformed to the compound of formula III. The anhydride yields a quantitative conversion of the compound of formula Ila to the compound of formula lib. Similar to the compound of formula Ila, the compound of formula lib is also thermally stable according to FIG.4.

[0099] The catalytic transformation is selective to the peroxy bond and does not react with the

double bonds of a compound of formula II: , wherein A is a C ₆ -C ₁₀ alkene chain with at least one double bond; ¹ is a Q-Cio alkyl; R ² is H or acetyl; and R ³ is an oxygen- containing functional group.

[00100] In some embodiments, the anhydride and amine-acid complex are added to a mixture containing the compound of formula Ila that is substantially free of the reagent. In another embodiment, the reagent in the mixture is less than 1 wt%. In yet another embodiment, the reagent in the mixture is less than 0.5 wt%.

[00101] In some embodiments, the conversion for the catalytic transformation from the compound of formula Ila to the compound of formula III is between 0 and 100%. In one embodiment, the conversion is in the range of about 0 to about 20%, about 20 to about 40%, about 40% to about 60%, about 60% to about 80%, about 80% to about 100%. In another embodiment, the conversion is at least 90%, preferably at least 95%», and more preferably at least 99%. The catalytic transformation may be conducted at temperatures less than 50°C, preferably range from about 0°C to about 50°C _} and more preferably from about 5°C to about 40°C.

[00102] The catalytic transformation is exothermic and, in some embodiments, the temperature of the reactor is maintained by a cooling system, such as an active jacketed cooler, to maintain a temperature of less than, e.g., 40°C. In some embodiments, the catalytic transformation may be conducted at a pressure from about 0 Psig to about 30 Psig. In other embodiments, the vacuum condition may be suitable when evaporative cooling is used. In a further embodiment, the catalytic transformation may be conducted at a pressure from about 0 Psig to about 5 Psig.

[00103] In some embodiments, the catalytic complex is an azeotropic acid-amine complex. This catalytic complex may be recovered from the product mixture via azeotropic distillation and recycled back to the transformation reactor. [00104] With reference to the Schreiber article, the disclosed process takes advantage of the stable azeotropic composition formed between the acid, amine and anhydride such that the equilibrated composition is recovered and recycled into the process. The Schreiber one-pot method is not suitable for commercial manufacturing as it fails to disclose or teach any efficient or economic means for recovering the recyclable components. In contrast, the disclosed process in this invention provides a practical and cost-effective continuous or batch process for commercial production.

[00105] The choice of molar addition ratio of the anhydride to amine will depend on the reaction conditions, namely, the contact time, temperature, pressure, heat removal, and such. In one embodiment, the molar ratio of anhydride to amine is from about 1 :50 to about 50:1. In another embodiment, the molar ratio of anhydride to amine is from about 1 :20 to about 20:1. In yet another embodiment, the molar ratio of anhydride to amine is from about 1 : 10 to about 10:1.

[00106] In some embodiments, the molar feed ratio of the amine to the compound of formula I is from about 1 :100 to about 10: 1, preferably from about 1 :25 to about 5:1, more preferably from about 1 :20 to about 2:1. In other embodiments, the molar feed ratio of the amine to the compound of formula I is from about 1:10 to about 2:1. In another embodiment, the molar feed ratio of the amine to the compound of formula I is from about 1 :2 to about 2: 1

[00107] In some embodiments, the molar feed ratio of the anhydride to the compound of formula I may be from about 1 :100 to about 100.T . In other embodiments, the molar feed ratio of the anhydride to the compound of formula I is from about 1:25 to about 25:1, In one embodiment, the molar feed ratio of the anhydride to the compound of formula I is from about 1 :10 to about 10:1. In another embodiment, the molar feed ratio of the anhydride to the compound of formula I is from about 1:5 to about 5: 1. In yet another embodiment, the molar feed ratio of the anhydride to the compound of formula I is from about 1 :3 to about 3:1.

[00108] In some embodiments, the catalytic complex may be fed to the enriched product stream at a temperature from about 0°C to about 50°C. [00109] In some embodiments, the catalytic complex may be fed in a batch-wise manner. In one embodiment, the catalytic complex is added in a continuous manner. In another embodiment, the catalytic complex is staged across the reaction zone.

[00110] One advantage of this stable azeotrope between acetic acid and triethylamine is that the mixture can be easily distilled and recycled back into the catalytic transformation step without further purification into its individual constituents. Fresh component make-ups are used to replenish the anhydride and amine levels as a result of reacted and/or fugitive losses. In some embodiments, the catalytic complex also serves as a carrier for the liberated acid from the catalytic transformation step. In other embodiments, the build-up of byproduct acid is purged from the azeotropic complex via distillation separation and the azeotropic complex is recycled back. Overall, we find the catalytic complex management is very simple and of high utilization with minimum waste streams.

[00111] As described above, the removal of the excess reagent prior to the catalytic transformation step at least eliminates, or in some embodiments, prevents the formation of acetate azeotropes. This advantage makes the purification of the compound of formula III more cost efficient. The '028 patent teaches a process wherein solvent extraction in the presence of methanol was used to recover the peroxidic monoozonolysis product from the biphasic liquid.

[00112] The disclosed process has found that the use of liberated acetic acid (derived from acetic anhydride) with triethyl amine is most preferred, as it advantageously offers the unique catalytic and processing features outlined above. The overall preservation of the species having at least the same number of carbon atoms as the compound of formula I is greater than 90%, e.g., greater than 95%. The overall selectivity to the non-selective products is less than 10%, e.g., less than 5%.

Process

[00113] FIG.l shows a non-limiting exemplary embodiment of the disclosed process involving the unit operations sequence as required herein. As shown in FIG. 1, ozonolysis effluent 11 comprising the compound of formula Ha, the compound of formula I, a reagent and by-products is collected in intermediate feed storage vessel 14 and maintained under an inert atmosphere at ambient temperatures for further processing. In one embodiment, storage vessel 14 has a sufficient capacity to supply a continuous catalyst transformation for at least 5 days, e.g., at least 10 days. The stable, flowable liquid of vessel 14 is fed to the first separation device 3 via stream 21. Separator 3 may comprise at least three theoretical stages. Separator 3 may be operated at or below 50°C and under reduced pressure, e.g., 0.05 torr to 30 torr, as determined by the concentration of stream 21. The vapor-liquid traffic in separator 3 is adjusted by refhixing and boil-up accordingly to the quality and quantity of feed from stream 21. The stripped reagent vapors from separator 3 are collected overhead and condensed into a liquid stream. In some embodiments, the reagent stream 23 may contain entrained low-boiling impurities and some of the compound of formula I as per the vapor-liquid equilibrium with the reagent. The crude, recovei-ed reagent is fed to a reagent purification column 6 via stream 23. The reagent-stripped, enriched product liquid from separator 3 is a one-phase flowable liquid which is fed to the catalytic transformation reactor 9 via stream 25.

[00114] In one embodiment, stream 25 comprises from 20 wt.% to 80 wt.% the compound of formula I, from 20 wt.% to 80 wt.% the compound of formula Ila, and from 0 wt.% to 20 wt.% the non-selective products. In some embodiments, stream 25 is substantially free of reagent that is removed by separator 3. In one embodiment, the compound of formula Ila is not isolated from the non-selective products or the compound of formula I.

[00115] The condensed reagent via stream 23 is taken to separator 6 for further purification. Separator 6 may be configured to effectively boil-off the purified reagent vapors based on the relative volatility with respect to the compound of formula I and other high-boiling constituents. A low-boiler purge is also taken in separator 6 to manage low-boiling impurities in the process. The purified reagent is taken from separator 6 via stream 31 which is made available for recycle. The residue liquid from separator 6 comprises the compound of formula I in majority which is made available for recycle via stream 35. Stream 35 may supply less than 5%, in some embodiments, between 2-3% of the compound of formula I, while Stream 43 recycles majority of the compound of formula I that is unconverted depending on the single-pass conversion achieved. The weight ratio of the entrained compound of formula I in Stream 35 to Stream 43 is not more than 5%. [00116] In device 9, a homogeneous liquid catalytic complex is fed via stream 49 and sufficient time and temperature are allowed for its contact with the liquid stream via 25. It is necessary to properly manage the exothermic heat of the transformation reaction which may be accomplished by controlled (or staged) addition of stream 49. Upon completion of the catalytic transformation of the compound of formula Ila in stream 25 to the compound of formula III, the liquid effluent containing the compound of formula III in entirety and all of catalytic complex are obtained via stream 27. In some embodiments, the non-selective products are also present in the liquid effluent.

[00117] In some embodiments of the disclosed process, a typical compositional profile of stream 27 may comprise from 20 to 50 wt.% of the compound of formula III, from 20 to 50 wt.% of the compound of formula I, and from 20 to 50 wt.% of catalytic complex including the stoichiometrically liberated acid. Stream 27 may also comprise minor amounts of other oxidized products, including non-selective alkenes and alkanes, in an amount from 0.01 to 5 wt.%., e.g., from 0.02 to 1.5 wt.%. In one embodiment, it is less than 5%, 4%, 3%, 2%, 1%, or 0.1%. In some embodiments, stream 27 is substantially free of the compound of formula Ila. In other embodiments, stream 27 is substantially free of the reagents, and thus the acetate azeotropes are also not present.

[00118] The elimination of excess reagents and the resulting acetate azeotropes, provides improved downstream process operation to recover the compound of formula III. The thermo- chemical properties of stream 27 allow it to undergo a separation in apparatus 12. It may be an apparatus such as a wiped-film evaporator (WFE), thin-film evaporator (TFE), short-path distillation (SPD), or combinations thereof. In some embodiments, the non-limiting conditions are in the temperature range from about 80°C to about 150°C, e.g., from about 90°C to about 140°C or from about 100°C to about 130°C, and reduced pressures in the range from about 0.1 kPa to about 5 kPa, e.g., from about 0.2 kPa to about 2.5 kPa. In one embodiment, the low- boiling vapors from 12 contain a majority of the compound of formula I and excess catalytic complex including the liberated acid component. The components separate out of the high- boiling components and are condensed via stream 55. The high-boiling liquid, substantially free of the compound of formula I and catalytic complex, is obtained as the concentrated compound of formula III via stream 51. [00119] The low-boiling constituents from apparatus 12 are further sent for separation via stream 55. Apparatus 15 may be configured to contain a series of phase separators and distillation columns to effectively separate the catalytic complex in an azeotropic composition via stream 45, the compound of formula I via stream 43 and the stoichiometric in-situ liberated acid via stream 41. In some embodiments, the acid in stream 41 may be recovered as a co- product.

[00120] Thus, the recovered catalytic complex as azeotropic mixture via stream 45 has shown sufficient catalytic activity whereby it may be fly-wheeled for multiple passes through apparatus 9. It is to be expected that the fugitive and reactive losses in the process are compensated by replenishing a fresh catalytic complex solution, comprising of an anliydride, amine and/or acid, via stream 61 on as-needed basis. Also, those skilled in the art will appreciate that typical process purge streams are to be taken out at appropriate locations for managing impurity buildups in the employed recycle loops.

[00121] Device 9 may provide high heat exchange surface area of such types as, but not limited to, shell-and-tube, plate-and-frame, micro-structure, double-pipe, cross-channel contacting devices for efficient heat transfer and uniform mixing. The device may have a provision for staged feed additions with inter-stage cooling as necessary. The device may also be equipped with an external pump-around loop for heat management.

[00122] In further embodiments, the steps are conducted in batch, semi-continuous, continuous processes or any combination thereof.

[00123] The liquid-liquid contacting devices in the disclosed process may comprise either agitated batch vessels, such co- and counter-current contacting columns as bubble columns, trickle bed columns, fluidized columns, random- or structured packed columns, micro-structure and/or continuous flow reactors with or without multiple feed injections for staged addition ports. Heat management is performed via internal heat transfer coils, external surface jackets, finned tube designs, and/or external circulation loops or combinations thereof,

[00124] For component flashing and separations based on the boiling-point differences, a variety of conventional and/or special gas-liquid separation devices are commonly used for this purpose. It is known to those skilled in the art of distillation separation that all forms and types of gas-liquid contacting stages, i.e., packed, plates, trays, and a combination thereof, would be suitable forms of providing the necessary theoretical separation stages in the process of this invention. Also, the conventional and improved forms of sub-cooled, heated and two-phase feed introduction, radial and axial distribution, and re-collection thereof shall apply to this application.

[00125] Another aspect of the disclosed process is directed to a method of making R ⁴ -A-R ⁴ comprising:

a) contacting a compound of fonnula I:o and a carboxylic acid with a medium comprising ozone;

b) forming an ozonolysis product, wherein the resulting ozonolysis product is not isolated; and

c) allowing the ozonolysis product to transform to R ⁴ -A-R ⁴ ;

wherein A is a C6-C ₁₀ alkene chain with at least one double bond and R ⁴ is an aldehyde group.

[00126] In some embodiments, the solvent is selected from the group consisting of _\ - alkyl acetates, Ci-C ₆ alcohols, ethers, DMF, DMAc, DMSO, NMP, THF, and mixtures thereof.

[00127] In some embodiments, the transformation in c) is in the presence of a catalyst. In other embodiments, the catalyst is selected from the salts of Ci-C ₆ carboxylic acids. In another embodiment, salts of alkyl amine and carboxylic acid may be used as the catalyst. In one embodiment, triethyl ammonium acetate may be used as the catalyst. In another embodiment, the catalyst system may be comprised of sodium acetate in acetic acid.

[00128] In some embodiments, A is a C ₆ or C ₁₀ alkene chain with at least one double bond. In one embodiment, A is a C ₁₀ alkene with two double bonds. In another embodiment, A is a C ₆ alkene with one double bond. [00129] Another aspect of the disclosed process is directed to a composition comprising a

compound of formula (II): ₅ wherein A is a C ₆ -Cio alkene chain with at least one double bond; R ¹ is a Ci-C ₁₀ alkyl; R ² is H, acetyl,; and R ³ is an oxygen-containing functional group.

[00130] In some embodiments, R ¹ is a Ci-C ₄ alkyl. In a further embodiment, R ¹ is a C2-C4 alkyl.

[00131] In some embodiments, A is a C ₆ or Cio alkene chain. In a further embodiment, A is a C<5 alkene chain. In another embodiment, A is a Cio alkene chain. In a further embodiment, A is a Cio alkene chain with two double bonds.

[00132] In one embodiment, R ² is H. In another embodiment, R ² is acetyl.

[00133] In some embodiments, R ³ is an aldehyde, an acid, or an ester group. In a further embodiment, R ³ is an aldehyde.

[00134] Another aspect of the disclosed process is directed to a composition comprising a

compound of fomiula (III): , wherein A is a C ₆ -Cio alkene chain with at least one double bond, R is a C1-C10 alkyl, and R is an oxygen-containing functional group.

[00135] In some embodiments, R ¹ is Q-C4 alkyl. In other embodiments, R ¹ is propyl or butyl.

[00136] In some embodiments, A is a C ₆ or Cio alkene chain. In a further embodiment, A is a C ₆ alkene chain. In another embodiment, A is a C ₁₀ alkene chain. In a further embodiment, A is - CH ₂ -CH2-CH=CH-CH2-CH2-CH=CH-CH2-CH ₂ -.

[00137] In some embodiments, R ³ is an aldehyde, an acid, an ester group. In a further embodiment, R ³ is an aldehyde. [00138] Another aspect of the disclosed process is directed to a method of making a compound

of formula Ha':

a) cont acting a compound of formula Γ: , and a reagent with a medium comprising ozone; b) forming a reaction mixture comprising the compound of formula Ila', and without isolating the product from the ozone of a); and c) recovering the product of b) comprising the compound of formula Ila'; wherein, B is a C ₆ -C ₁₀ alkylene chain R ¹ is a Ci-Cio alkyl; R ³ is an oxygen-containing functional group.

[00139] In some embodiments, R ¹ is a Cj-Cg alkyl. In another embodiment, R ¹ is a C ₂ -C ₄ alkyl. In a further embodiment, R ¹ is propyl or butyl.

[00140] In some embodiments, R ³ is an aldehyde, an acid, or an ester group. In a further embodiment, R ³ is an aldehyde or an acid group. In another further embodiment, R ³ is an aldehyde group.

[00141] The compound of formula Γ may include cyclic olefins. In some embodiments, the compound of formula Γ is a cycloalkene having between eight and twelve carbon atoms in the molecular structure. Examples of the compound of formula Γ include, but are not limited to, cyclohexene, cycloheptene, cyclooctene, cyclononene, cyclodecene, cycloundecene, cyclododecene, including isomers and mixtures thereof. In some embodiments, the compound of formula Γ is cyclododecene or cyclooctene. In another embodiment, the compound of formula Γ is a cyclooctene, including cis/trans isomers and mixtures thereof. In another further embodiment, the compound of formula Γ is a cyclododecene, including cis/trans isomers and mixtures thereof. [00142] In some embodiments, the compound of formula Γ has a purity of at least 90%. In other embodiments, the compound of formula Γ has a purity of at least 95%. In a further embodiment, the compound of formula Γ has a purity of at least 98%. In another further embodiment, the compound of formula Γ has a purity of at least 99%.

[00143] In some embodiments, the reagent is a Ci-C ₁₀ alcohol. In other embodiments, the reagent is chosen from a class of primary, secondary, tertiary alcohols, and mixtures thereof. In some other embodiments, the reagent is chosen from methanol, ethanol, 1-propanol, 2-methyl- propan-l-ol (iso-butanol), 2-methyl-2-propanol, 1-butanol, and mixtures thereof. In yet other embodiments, the reagent is chosen from 2-propanol, 2-butanoI, 3-pentanol, and mixtures thereof. In some other embodiments, the reagent is chosen from 2-methyl-2-propanol, 2-methyl- 2-butanol, tert-butanol, and mixtures thereof. Higher alcohols such as butanols, etc., are preferred.

[00144] In some embodiments, the reagent is anhydrous, preferably contains less than 0.5 wt.% water, or more preferably less than 0.1 wt.% water, In other embodiments, the water content may be no more than 0.08 wt.%, preferably no more than 0.04 wt.%.

[00145] In some embodiments, the amount of the reagent may vary and generally excess reagent may be used. For purposes of the disclosed process, the molar ratio of the compound of formula Γ to the reagent may be about 100:1 to about 1 : 100, preferably about 25:1 to about 1:25, and more preferably about 10:1 to about 1 :10. In one embodiment, the molar ratio of the compound of formula Γ to the reagent is about 4:1 to about 1 :10. In another embodiment, the molar ratio of the compound of formula Γ to the reagent is about 6:1 to about 1 :6. In yet another embodiment, the molar ratio of the compound of formula Γ to the reagent is about 3 : 1 to about 1 :3.

[00146] In one embodiment, the reagent is provided in excess. In this context, the term "excess" is defined as the molar amount of the reagent that is more than the reacted compound of formula I'. In some embodiments, the method further comprises at least partially removing the excess reagent in c). In a further embodiment, majority of the excess reagent is removed in c). In some embodiments, the excess reagent is removed via flash distillation. In some embodiments, the removed reagent from c) is partially or totally recycled back to a). In another embodiment, the removed reagent of c) is refined and purified.

[00147] In some embodiments, steps a) through c) are performed in a single continuous phase. In other embodiments, the reagent is provided in the quantity at least sufficient to react to a desired conversion at the conditions of a). In an embodiment, the reagent is provided to improve flowability characteristics of the reaction medium. In another embodiment, the reagent is provided to improve the heat transfer properties of the reaction medium.

[00148] In some embodiments, steps a) through c) may be conducted in the presence of an optional inert solvent. In other embodiments, the inert solvent is a polar solvent. Examples of the suitable polar solvent include, but are not limited to, Ci-C ₆ alkyl acetates, ethers, dimethyl formamide (DMF), dimethyl acetamide (DMAc), dimethyl sulfoxide (DMSO), n-methyl pyrrolidinone (NMP), tetrahydrofuran (THF), and mixtures thereof.

[00149] In some embodiments, the concentration of the compound of formula Γ in the reaction zone, by weight, may be about 0.1% to 99.9% range. In one embodiment, the compound of formula Γ is present in the about 0.5%-25% concentration range. In other embodiments, the compound of formula Γ is present in the about 25%-35%, in the about 35%-45%, in the about 45%-55%, in the about 55%-65%, in the about 65%-75%, in the about 75%-85%, in the about 85%-95%, or in the about 95-99.9% concentration range. In some embodiments, the compound of formula Γ concentration range may be from about 1% to about 99%. In a further embodiment, the compound of formula Γ concentration range may be from about 10% to about 90%. hi another further embodiment, the compound of formula Γ concentration range may be from about 25% to about 85%, preferably from about 30% to about 75%, and more preferably from about 30% to about 65%. In one embodiment, the compound of formula Γ is from about 35% to about 60% by weight.

[00150] The ozone-containing gas may comprise a mixture of ozone and at least one earner gas. The amount of ozone may vary. In some embodiments, ozone may be from about 0.01 mol.% to about 100 mol.%. In a further embodiment, ozone may be from about 0.1 mol.% to about 10 mol.%, from about 10 mol.% to about 30 mol.%, from about 30 mol.% to about 50 mol.%, from about 50 mol.% to about 70 mol.%, from about 70 mol.% to about 90 mol.%, or from about 90 mol.% to about 100 mol.%. In other embodiments, ozone may be from about 0.1 mol.% to about 25 mol.%. In a further embodiment, ozone may be from about 1 mol.% to about 20 mol.%. In another further embodiment, ozone may be from about 1 mol.% to about 15 mol.%.

[00151] In some embodiments, the carrier gas may be selected from the group consisting of nitrogen, argon, carbon dioxide, oxygen, air, and mixtures thereof. In one aspect, the ozone- containing gas may comprise ozone, oxygen, and argon. In one embodiment, the ozone- containing gas may comprise ozone, oxygen, and nitrogen. In another embodiment, the ozone- containing gas may comprise ozone and carbon dioxide. There is no restriction on which carrier is to be used so long as it is chemically compatible with ozone and the carrier itself does not lead to undesirable reactions with the hydrocarbon substrate.

[00152] In some embodiments, the ozone may be introduced in the dissolved state using an appropriate solvent. In other embodiments, the concentration of ozone may be enriched by injecting ozone into a pressurized circulation loop.

[00153] In some embodiments, the medium comprising ozone may be further enriched to obtain a concentrated ozone feed. Suitable forms of ozone enrichment may include the use of materials having the ozone affinity, such as the packed beds, solvents. In other embodiments, the ozone may be selectively separated and concentrated from the medium comprising dilute concentrations of ozone.

[00154] In some embodiments, the concentration of ozone in the ozone-containing medium, by weight, may be from about 0.01% to about 100%. In other embodiments, the ozone concentration may be from about 0.5% to about 5%, from about 5% to about 25%, from about 25% to about 50%, from about 50% to about 75%, from about 75% to about 100%.

[00155] In some embodiments, the total addition of ozone is at least partially influenced by the desired conversion and efficiency of ozone take-up. The ozone-containing gas is passed through the reaction solution for a period of time sufficient to permit selective cleavage of only one double bond. In some embodiments, the period of time may range from about 10 minutes to about 300 minutes. In a further embodiment, the period of time may range from about 30 minutes to about 200 minutes. The total ozone fed to the process can be sub-stoichiometric, stoichiometric or excess with respect to the one double bond in the compound of formula Γ that is converted. In one example, the total moles of ozone fed to the process are in the stoichiometric ratio with respect to the moles of one double bond in the compound of formula Γ that is converted.

[00156] The contacting step can be earned out for a suitable time determined by a reasonable amount of trial and error. For example, an embodiment includes introducing a flow of gas during a time period that is from about 40 minutes to about 240 minutes. In another embodiment, a flow of gas is introduced during a time period that is from about 5 minutes to about 500 minutes or more. In a batch configuration the ozone addition time is at least partially influenced by the flow rate of ozone (moles per mole of cyclic alkene per minute), the desired conversion and the efficiency of ozone uptake.

[00157] The flow rate of ozone fed may depend on the scale of operation and the desired conversion within the reaction time chosen. In some embodiments, the ozone flow rate is in the range from about 0.001 g/min to about 1 g/min. In a further embodiment, the ozone flow rate is in the about 0.005 g/min to about 0.8 g/min range. In another further embodiment, the ozone flow rate is in the about 0.01 g/min to about 0.2 g/min range. In yet another further embodiment, the ozone flow rate is in the about 0.02 g/min to about 0.1 g/min range.

[00158] The readers may appreciate that there is no limit as such on either the ozone feed rate, ozone concentration or the contact time. The described ranges are non-limiting and those skilled in the art may appreciate the even broader ranges that may be required to achieve the desired conversion, product yields and reaction heat management at various production scales.

[00159] In some embodiments, a sufficient quantity of ozone may be generated from a chemical conversion device such as Ultraviolet (UV) converter, Corona Discharge conveiter, etc. The source of elemental oxygen for ozone generation may be selected from diatomic oxygen, carbon monoxide, carbon dioxide, nitrogen oxides, water, oxygenated chemicals, air and like. In one embodiment, pure oxygen may be used for the ozone generation. In another embodiment, carbon dioxide may be used for the ozone generation. In yet another embodiment, oxygen generated from a water electrolysis device may be fed to the ozone generator. In one embodiment, an oxygen-rich offgas from a chemical process may be used for the ozone generation. Examples of such chemical processes may include, but are not limited to, oxidation, combustion, aerobic, fuel-cells, absorption, fermentation, etc.

[00160] In some embodiments, the conversion of the compound of formula Γ is from about 0% to about 100%. In a further embodiment, the conversion of the compound of formula Γ is from about 1% to about 99.9%. In other further embodiments, the conversion of the compound of formula Γ is from about 2% to about 99.5%, from about 3% to about 99%, or from about 4% to about 98.9%. hi other embodiments, the conversion of the compound of formula Γ is at least 90%. In a further embodiment, the conversion is at least 95%. In another further embodiment, the conversion is at least 96%, 97%, 98%, 99% or 100%.

[00161] In one embodiment, the conversion may be performed sequentially, i.e. , the compound of formula Γ, and an optional inert solvent, is contacted first with medium comprising ozone to produce an ozonolysis product. The ozonolysis product may be further contacted with a medium comprising a reagent to obtain the desired product. In another embodiment, the conversion may be performed concurrently. In yet another embodiment, the conversion may be performed partially or completely.

[00162] The term "selectivity" for a compound defined as a percent means: [Number of moles of the compound formed during steps a-c)] / [Number of moles of the compound of formula Γ converted during steps a-c)] x 100. For reaction mixtures comprising more than one formed compound during steps a-c), the selectivity is normalized.

[00163] In some embodiments, the compound of formula Ila ¹ is formed with a selectivity of at least 50%. In other embodiments, the compound of formula Ila' is formed with a selectivity of at least 60%. In another embodiment, the compound of formula Ila' is formed with a selectivity of at least 70%. In other embodiments, the selectivity for the compound of formula Ila' is at least 80%. In another embodiment, the selectivity for the compound of formula Ila' is at least 85%. In a further embodiment, the selectivity for the compound of formula Ila' is at least 90%. In another further embodiment, the selectivity for the compound of formula Ila' is at least 95%. [00164] In some embodiments, the ozonolysis reaction may be conducted at a temperature of less than 50°C, preferably from about -25°C to about 50°C, from about -25°C to about 50°C, from about -20°C to about 50°C, from about -15°C to about 50°C, from about -10°C to about 50°C, from about 0°C to about 45°C, preferably from about -10°C to about 40°C, and more preferably from about -10°C to about 35°C. The ozonolysis reaction is exothermic and, in some embodiments, the temperature of the reactor is maintained by a cooling system, such as an active jacketed cooler.

[00165] Pressures can be above or below atmospheric, and are selected to maintain the cyclic alkene feed in the liquid phase and the ozone-containing gas in the gaseous phase. In some embodiments, the ozonolysis reaction may be conducted at a pressure from about 100 torr to about 200 Psig. In other embodiments, the ozonolysis reaction may be conducted at a pressure from about 100 ton- to about 100 Psig. In a further embodiment, the ozonolysis reaction may be conducted at a pressure from about 0 Psig to about 50 Psig, preferably from about 0 Psig to about 25 Psig, more preferably from about 0 Psig to about 20 Psig, and most preferably from about 0 Psig to about 10 Psig.

[00166] In some embodiments, the sub-atmospheric pressure may be used when the reaction heat is removed by above-surface solvent evaporation, commonly referred to as evaporative cooling. In other embodiments, the reaction off-gas vent may be scrubbed by the suitable means and the entrained organics recovered for re-use. In one embodiment, the incoming feeds, indigenous to the process, may be appropriately contacted with the reactor offgas in a manner sufficient to perform the scrubbing of the condensables away from the non-condensables. In another embodiment, a new medium that is non-reactive but effective at scrubbing may be introduced as an agent.

[00167] In one embodiment, the compound of formula Ila' is formed from ozonolysis of cyclododecene, wherein B is -CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-. h another embodiment, the compound of formula Ila' is formed from ozonolysis of cyclooctene, wherein B is -CH ₂ -CH2-CH ₂ -CH ₂ -CH2-CH ₂ -. [00168] Another aspect of the disclosed process is di d for transforming the

compound of formula Ila' to a compound of formula I : , wherein B is a Q-Qo alkylene chain, R ¹ is a C]-Cio alkyl, and R ³ is an oxygen-containing functional group, without forming an acetate side product.

[00169] In some embodiments, R ¹ is a Ci-C& alkyl. In another embodiment, R ¹ is a C ₂ -C ₄ alkyl. In a further embodiment, R ¹ is propyl or butyl.

[00170] In some embodiments, B is a C ₆ or C ₁₀ alkylene chain. In one embodiment, B is a C ₁₀ alkylene chain. In another embodiment, B is a C ₈ alkylene chain. In yet another embodiment, B is a C ₆ alkylene chain.

[00171] In some embodiments, R ³ is an aldehyde, an acid, or an ester group. In a further

3 3 embodiment, R is an aldehyde or an acid group. In another further embodiment, R is an aldehyde group.

[00172] In one embodiment, the transformation of the compound of formula Ha' to the compound of formula IV is in the presence of an acid anhydride. Examples of suitable anhydrides include, but are not limited to, acetic anhydride, succinic anhydride, maleic anhydride, other anhydrides belonging to the general anhydride family and mixtures thereof. Acetic anhydride is preferred.

[00173] In some embodiment, the transformation of the compound of formula Ha' to the compound of formula IV is in the presence of a catalyst. In other embodiments, the catalyst is homogenous. In a further embodiment, the catalyst is a mixture of acid and amine. In another embodiment, the amine and the acid can be freshly mixed, premixed, azeotropically co-distilled, or recycled.

[00174] Examples of suitable acids include, but are not limited to, acetic acid, succinic acid, maleic acid. In a further embodiment, the acid is acetic acid. [00175] In some embodiments, the amine is compatible with the acid and suitable for driving base-catalyzed reactions.

[00176] In some embodiments, the amine may be a hindered secondary amine. In other embodiments, the amine may be a teitiaiy amine. In some other embodiments, the amine may be a cyclic amine.

[00177] In some embodiments, the amine may be represented by a quaternary ammonium cation; commonly known as the "quaternary amines". In quaternary amines, there are four organic substituents, such as alkyl, aryl or both, attached to the charged nitrogen center. Examples may include quaternary ammonium salts with a variety of anions.

[00178] hi some embodiments, the amine may be represented by a biogenic substance with one or more amine groups; commonly known as the "biogenic amines". Biogenic amines are nitrogenous organic bases and are synthesized by microbial, enzymatic, vegetable and animal metabolism routes.

[00179] The tertiary amines are those in which all three hydrogen atoms are replaced by organic substituents, such as alkyl, aryl or both. Examples of tertiary amines include, but are not limited to, trialkyl amines such as trimethy-, triethyl-, tripropyl-, tributyl-lamine, and aromatic tertiary amines such as Mphenylamine.

[00180] Examples of suitable amines include, but are not limited to, triethyl amine, diethanol amine, tributyl amine, pyridine, other unsubstituted or substituted amines belonging to the general amines family and mixtures thereof. Triethyl amine is preferred.

[00181] In some embodiments, the molar ratio of acid and amine may range from about 1 :100 to about 100:1. In one embodiment, the molar ratio of acid and amine may range from about 1 :25 to about 25:1. In another embodiment, the molar ratio of acid and amine may range from about 1 :10 to about 10:1. In a further embodiment, the molar ratio of acid and amine may range from about 1:6 to about 6:1. In yet another embodiment, the molar ratio of acid and amine is about 1 :1. [00182] In some embodiments, the necessity of using acetic anhydride and ethyl amine in the transformation reaction may be removed by replacing with either a homogeneous or heterogeneous catalytic system. In one aspect, the catalytic systems have nucleophilic / basic characteristics. These properties may be comprised into one system or be discrete entities and admixed.

[00183] In some embodiments, molecular sieves, zeolites, mesoporous and microporous materials may be comprised into the catalytic systems. In other embodiments, mesoporous systems such as MCM-41, MCM-48, and SBA-15 may be comprised into the catalytic systems. In one embodiment, Zeolites X and L may be comprised into the catalytic systems. In another embodiment, ion-exchange of the solid materials with alkali metals such as K, Rb, and Cs may be conducted. In yet another embodiment, solid materials may be functionalized with amines via grafting and intercalation. In one aspect, basic nucleophiles may be incorporated into the frame work of the material.

[00184] In some embodiments, the catalyst can be basic zeolites, mesoporous materials, microporous materials, materials with both mesoporous and microporous characteristics, and combinations thereof.

[00185] In some embodiments, the catalyst(s) and mixtures thereof are promoted and/or are comprised of functional groups, e.g. an amine. In other embodiments, the catalyst functional groups are basic and include lone pair electrons on heteroatoms including O, N, P, B and S.

[00186] In some embodiments, a drying agent may be physically mixed with the catalyst. In other embodiments, the diying agent may be comprised of silica gel and/or molecular sieves, especially, 4 A and 5 A.

[00187] In one embodiment, the transformation is in the presence of a mixture of an acid and a base. In one embodiment, the base can be an inorganic base. Examples of the suitable inorganic base include, but are not limited to, KOH, K ₃ PO ₄ , KF, CsF, NaOAc and OAc. [00188] In some embodiments, the compound of formula Ila' first transforms to a compound of

formula lib': before the compound of formula IV is formed, wherein R is an acetyl group.

[00189] In some embodiments, the transformation is conducted under substantially solvent free condition. In a further embodiment, the transformation is in the absence of a solvent. In other embodiments, the transformation is in the presence of an inert solvent. Examples of the suitable inert solvent include, but are not limited to, C]-C ₆ alkyl acetates, Ci-C ₆ alcohols, ethers, acetic acid, succinic acid, maleic acid, DMF, DMAc, DMSO, NMP, THF, and mixtures thereof.

[00190] In one embodiment, the transformation is in the presence of the compound of formula

Γ.

[00191] o a method of making a compound

of formul a. contacting a compound of formula Γ: and a reagent with a medium

comprising ozone to form a compound of formula Ila': ; and b. allowing the compound of formula Ila' transform to the compound of formula IV, without forming an acetate side product;

wherein, B, R 1 , and R 3 are defined as described above.

[00192] In one embodiment, the reagent is provided in excess, hi this context, the term "excess" is defined as the molar amount of the reagent is more than the reacted compound of formula I. In some embodiments, the method further comprising at least partially removing the excess reagent prior to b). In a further embodiment, majority of the excess reagent is removed prior to b). In some embodiments, the excess reagent is removed via flash distillation. In another embodiment, the catalyst is at least partially removed with the reagent. In a further embodiment, majority of the catalyst is removed. In some embodiments, the removed catalyst and/or reagent are recycled back to the process.

[00193] In some embodiments, the transformation is in the presence of a catalyst.

[00194] isclosed process is directed to a method of making a compound

of formul comprising: a) contacting a compound of formula Γ: and a reagent with a medium comprising ozone to form a mixture comprising a compound of formula Ila': and the reagent;

b) exposing the mixture to a combination of temperature and pressure such that the reagent flashes to increase concentration of Formula Ila' in the mixture without thermally degrading the compound of formula Ila' component of the mixture; c) contacting the concentrated mixture comprising the compound of formula Ila' with an acid anhydride and an amine; and

d) recovering a product comprising the compound of formula IV;

wherein, B is a C ₆ -Cio alkylene chain, R ¹ is a Q-Cio alkyl, and R ³ is an oxygen-containing functional group.

[00195] In some embodiments, the excess reagent may be distilled off at about 50°C under reduced pressure without any measurable decomposition and thus no measurable yield loss. In an embodiment, the excess reagent may be removed at about 15°C to about 60°C temperature range and the pressure range of about 0 torr to about 100 torr. In another embodiment, the excess reagent may be removed at about 25°C to about 55°C temperature range and the pressure range of about 0.05 to about 30 torr. The net impact is an improved overall process with a simpler backend separations scheme not having to deal with the azeoti-opes of alcohols, acetates and acids, the ability to cleanly recycle the catalyst, and recovery of the excess reagent in support of either continuous or batch processing without negative impact on the process. Thus, the ozonolysis products do not need to be separated and isolated from the ozonolysis effluent. This leads to further improved efficiencies in the process.

[00196] Advantageously, the disclosed process does not require isolating the compound of formula Ila' prior to the catalytic transformation step. Instead, the excess reagent and, optionally, a small portion of the compound of formula Γ are removed before the catalytic transformation step. The mixture comprising the compound of formula Ila' and the compound of formula Γ is passed along to the catalytic transformation step.

[00197] In some embodiments, after the excess reagent is removed, the enriched product stream is catalytically transformed in the presence of a catalyst to form the compound of formula IV. In other embodiments, a homogeneous catalyst complex was used for the catalytic transformation reaction. In yet another embodiment, a heterogeneous catalyst may be used for the transformation reaction.

[00198] In some embodiments, the compound of formula lib' is first formed from the reaction of the compound of formula Ila' with an anhydride. The compound of formula lib' is then contacted with the homogeneous catalytic complex generated "in-situ" from stoichiometrically liberated acid and added amine to be catalytically transformed to the compound of formula IV. The anhydride yields a quantitative conversion of the compound of formula Ila' to the compound of formula lib'. Similar to the compound of formula Ila', the compound of fonnula lib' is thermally stable at our processing conditions.

[00199] In some embodiments, the anhydride and amine-acid complex are added to a mixture containing the compound of formula Ila' that is substantially free of the reagent. In another embodiment, the reagent in the mixture is less than 1 wt%. In yet another embodiment, the reagent in the mixture is less than 0.5 wt%. [00200] The catalytic ansformation is exothermic and, in some embodiments, the temperature of the reactor is maintained by a cooling system, such as an active jacketed cooler, to maintain a temperature of less than, e.g., 40°C. In some embodiments, the catalytic transformation may be conducted at a pressure from about 0 Psig to about 30 Psig. In other embodiments, the vacuum condition may be suitable when evaporative cooling is used. In a further embodiment, the catalytic transformation may be conducted at a pressure from about 0 Psig to about 5 Psig.

[00201] In some embodiments, the catalytic complex is an azeotropic acid-amine complex. This catalytic complex may be recovered from the product mixture via azeotropic distillation and recycled back to the transformation reactor.

[00202] The choice of molar addition ratio of the anhydride to amine will depend on the reaction conditions, namely, the contact time, temperature, pressure, heat removal, and such. In one embodiment, the molar ratio of anhydride to amine is from about 1 :50 to about 50:1. hi another embodiment, the molar ratio of anhydride to amine is from about 1 :20 to about 20:1. In yet another embodiment, the molar ratio of anhydride to amine is from about 1:10 to about 10:1.

[00203] In some embodiments, the catalytic complex may be fed to the enriched product stream at a temperature from about 0°C to about 50°C.

[00204] In some embodiments, the catalytic complex may be fed in a batch-wise manner. In one embodiment, the catalytic complex is added in a continuous manner. In another embodiment, the catalytic complex is staged across the reaction zone.

[00205] One advantage of this stable azeotrope between acetic acid and triethyl amine is that the mixture can be easily distilled and recycled back into the catalytic transformation step without further purification into its individual constituents. Fresh component make-ups are used to replenish the anhydride and amine levels as a result of reacted and/or fugitive losses. In some embodiments, the catalytic complex also serves as a earner for the liberated acid from the catalytic transformation step. In other embodiments, the build-up of byproduct acid is purged from the azeotropic complex via distillation separation and the azeotropic complex is recycled back. Overall, we find the catalytic complex management is very simple and of high utilization with minimum waste streams. [00206] As described above, the removal of the excess reagent prior to the catalytic transformation step at least eliminates, or in some embodiments, prevents the formation of acetate azeotropes. This advantage makes the purification of the compound of formula IV more cost efficient.

[00207] The disclosed process has found that the use of liberated acetic acid (derived from acetic anhydride) with triethyl amine is most preferred, as it advantageously offers the unique catalytic and processing features outlined above,

[00208] In some embodiments, the compound of formula III may be non-catalytically or catalytically hydrolyzed into its corresponding acid, wherein R ¹ is hydrogen. Hydrolysis may be performed in the hot water, boiling water, organic solvent, and/or in the absence or presence of a catalyst. Suitable catalysts may include mineral acids and bases. In other embodiments, an acid equivalent of the compound of formula III may be transformed into its corresponding amine derivative, which may serve as another monomer of some commercial value.

[00209] In some embodiments, the compound of formula IV may be transformed into its corresponding amine derivative, which may serve as another monomer of some commercial value.

[00210] Another aspect of the disclosed process is directed to a method of making R -B-R ⁴ comprising:

contacting a compound of formula Γ: and an agent with a medium comprising ozone; forming an ozonolysis product, wherein the resulting ozonolysis product is not isolated; and allowing the ozonolysis product to transform to R ⁴ -B-R ⁴ ; wherein B is a C ₆ -Cio alkylene chain and R ⁴ is an aldehyde group.

[00211] In some embodiments, the transformation is in the presence of a catalyst. In other embodiments, the catalyst is selected from the salts of CpCg carboxylic acids. In another embodiment, salts of alkyl amine and carboxylic acid may be used as the catalyst. In one embodiment, triethyl ammonium acetate may be used as the catalyst. In another embodiment, the catalyst system may be comprised of sodium acetate in acetic acid.

[00212] In some embodiments, the contact between the compound of formula Γ and the reaction medium may be established using multi-phase contacting devices that are commonly known in the chemicals manufacturing industry. Examples are tower column, horizontal contactor, packed column, trickle-bed column, CSTR, tube reactor, bubble column, static mixer, jet reactor, micro -structure reactor, and variations thereof. The devices may be used alone, in sequence, in parallel or as combination of two or more. The described examples are non-limiting and those skilled in the art may appreciate all arrangement variations of such multi-phase contacting devices to achieve an efficient exchange of materials and heat which may result in acceptable product yields and quality. Whichever the arrangement may be, readers may also recognize that achieving a safe operation is the primary objective from a commercial standpoint.

[00213] In some embodiments, the contact between the compound of formula Γ and ozone medium may be carried out in a counter-current flow mode. The counter-current flow mode means the two or more reacting phases are traveling in the opposite direction of each other. In other embodiments, the contact may occur in a co-current flow mode. The co-current flow mode means the two or more reacting phases are travelling in the same direction of each other. Other flow modes for the contact may include, but not limited to, sparged-flow, cross-flow, up-flow, down-flow, laminar-flow, turbulent-flow, thin film-flow, dispersion-flow, circulatory-flow, and combinations thereof.

[00214] In some embodiments, the contacting device may be equipped with an external or internal loop-around for efficient mixing and heat exchange. In one embodiment, the ozone medium may be introduced in the high-turbulence, loop-around section of the contacting device. In another embodiment, the ozone medium may be introduced through a distribution system across the reaction zone. In yet another embodiment, the ozone medium may be staged across the reaction zone to develop the desired spatial concentration profiles.

[00215] In one embodiment, the medium comprising ozone may be appropriately introduced to minimize the ozone entrainment in the gas-phase and to minimize aerosol formation. In another embodiment, the liquid droplets (or aerosol) from the offgas vent may be trapped and removed from the gas space. Most commonly used trapping devices include mist eliminator, aerosol coalescing section, spray section, cyclone separator, baffled serpentine flow section, and combinations thereof. The trapping section may or may not be temperature controlled. The trapped material may be returned back to the reaction zone or diverted for recovery.

[00216] In some embodiments, the reactor off-gas comprising the entrained hydrocarbons, ozone, oxygen may be adequately treated with the use of non- catalytic or catalytic thermal oxidation (TO), physical or chemical scrubbing, bio-ponds, and other known industrial abatement techniques. In another embodiment, the offgas may be fed to a co-gen facility for the fuel value recovery. In yet another embodiment, the offgas may be a useful organic food for a biological cell culture. In a further embodiment, the offgas may be an effective oxygen-rich feed for the solid-oxide fuel cell power generation system.

[00217] Examples of the suitable agent include, but are not limited to water, carboxylic acid, DMSO, water/manganese diacetate, 4.1-9.6 pH buffer solutions. Examples of the carboxylic acid include, but are not limited to, acetic acid, succinic acid, maleic acid. In some embodiments, the agent is water or carboxylic acid. In a further embodiment, the agent is water. In yet another embodiment, the agent is acetic acid.

[00218] In some embodiments, the agent in the reaction mixture is about 0.1 % to about 99% by weight. In a further embodiment, the agent in the reaction mixture is about 5% to about 80% by weight.

[00219] In some embodiments, the amount of the agent may vary and generally excess agent may be used. For purposes of the disclosed process, the molar ratio of the agent to the compound of formula Γ may be about 500: 1 to about 1 :100, preferably about 400:1 to about 1 :75, and more preferably about 300:1 to about 1 :50. In one embodiment, the molar ratio of the agent to the compound of formula Γ is about 250:1 to about 1 :30. In another embodiment, the molar ratio of the agent to the compound of formula Γ is about 225:1 to about 1:25. In yet another embodiment, the molar ratio of the agent to the compound of formula Γ is about 200: 1 to about 1 :20. [00220] In some embodiments, the obtained dialdehyde from the compound of formula Γ may be further transformed into a diamine. The diamine functionality is of some commercial value and may be used as a monomer to polymerize into a polyamide of commercial importance.

[00221] In some embodiments, the dialdehyde obtained from the compound of formula Γ may serve as a useful raw material for making products comprising; diacids, diols, diesters, aldehyde acids, hydroxyl acids, ester acids, hydroxyl esters, and mixtures thereof. In one embodiment, the dialdehyde may be partially or completely oxygenated into an aldehyde acid, diacid, and mixtures thereof. In another embodiment, the dialdehyde may be partially or completely hydrogenated to hydroxyl aldehyde, diol, and mixtures thereof In yet another embodiment, the diacid, obtained from the dialdehyde, may be partially or completely esterified to an acid ester, diester and mixtures thereof.

Analytical Methods

[00222] Analysis is conducted using an Agilent 7890A GC with an FID. The GC column is an Agilent DB-1 column, 60 meter long with a diameter of 0.32 micron and a film thickness of 1.00 micron. NMP is used as the internal standard. Typically, the injection volume is 1 microliter. The injection port temperature is 250°C with an inlet pressure of 10.0 psi. The total Helium flow is 11 ml/min with a split ratio of 10:1. The GC oven ramp program is typically; 40°C initial temp, (no hold time); 10°C/min ramp rate; 200°C (15 min. hold time); 10°C/min ramp rate; 275°C final temp. (15 min. hold time). The detector is set at 275°C with a Hydrogen flow of 40 ml/min, 400 ml/min air, 24 ml/min Helium make up. The reaction product is analyzed for various organic compounds. In addition, samples are derivatized using Ν,Ο- Bis(trimethylsilyl)trifluoroacetamide (BSTFA) in order to detect and quantify carboxylic acid type products. The GC data is used to determine the weight percent of starting material and products. The weight percent data are used to calculate conversion of starting material and the molar selectivity for various products.

[00223] The DSC characterization of the compounds disclosed in the disclosed process Examples is performed using a Q200 Series™ standard-cell Differential Scanning Calorimeter, manufactured by TA Instruments. The Q200 DSC instrument provides the temperature measurement accuracy of ± 0.1°C and the temperature precision of ± 0.05°C. The calorimetric reproducibility (Indium metal) is ± 0.1% with the calorimetiic precision (Indium metal) of ± 0.1%. The Q200 DSC instrument sensitivity for heat flow measurements is 0.2 μψ.

[00224] The Nuclear. Magnetic Resonance (NMR) characterization of the compounds disclosed in the disclosed process, is performed using a Bruker AV400 NMR spectrometer with a QNP CryoProbe. The NMR sample tubes used for these measurements are 5 -mm in diameter. A total of 16 scans are co-added for 1H experiments, while 1024 scans are collected for ¹³ C experiments. In 1H experiments, 30 degree tipping angle is used with a relaxation delay of 1.5 seconds. For ^I3 C experiment, standard proton decoupling is applied throughout the relaxation delay and data acquisition period.

[00225] The following Examples further demonstrate the disclosed process and its capability for use. The invention is capable of other and different embodiments, and its several details are capable of modifications in various apparent respects, without departing from the scope and spirit of the disclosed process. Accordingly, the Examples are to be regarded as illustrative in nature and not as restrictive. All percentages are by weight unless otherwise indicated.

[00226] Example 1: A 00mL jacketed round-bottom flask is fitted with a dry ice condenser, mechanical stirrer, stainless steel feed tube for sub-surface ozone gas addition and a fourth port for addition of reagents, sampling and thermocouple connection. A dry gas mixture containing 21% oxygen in argon is fed to an ozone generator (Pacific Ozone). The exit gas from the ozone generator is flowed through an ozone monitor (Teledyne Instruments) for 30min to obseive stable ozone concentration in the feed gas. The reaction temperature is maintained at a desired target via jacketed cooling. The exit gas containing residual oxygen and argon are passed through a dry ice cold trap to recover any low-boiling components. Upon reaction time completion, dry nitrogen is passed into the reactor for 30min to displace any residual ozone and oxygen and the vessel is warmed to room temperature. 1,5,9-cyclododecatriene (CDDT) is used as received from INVISTA™ Specialty Intermediates. Table 1 depicts a typical composition. Table 1

Typical Composition, wt°/o

1,5,9-Cyclododecatriene >99

Tert-butyl catechol 30-50 ppm

isomers

cis, trans, trans 98

trans, trans, trans 1.5

cis, cis, trans 0.3

cis, cis, cis 0.1

[00227] A steady concentration of 26.3g ozone/m ³ in 3 liter/min argon flow is sparged into the reaction vessel for 114 minutes containing 60g (0.37 mole) of 1,5,9-cyclododecatriene (CDDT) and 27.4g of fresh, dry n-butyl alcohol. The reaction is carried out at 5.0°C bulk temperature. When the reaction is complete, excess alcohol is flashed off at 50°C and under vacuum. To the concentrated reaction intermediate a cooled liquid mixture of 35.2g acetic anhydride and 7.5g triethylamine is added via pump at an average feed rate of 2.67 g/min with 650 RPM stiixing of the reaction mixture. The reaction exotherms, observed during these additions, are managed by active jacketed cooling to ensure the temperature is maintained at or below 40°C. The reaction mixture is allowed to reach room temperature and is stirred for additional 30 minutes for completion. 112g of one-phase liquid reaction product was recovered. The final GC analysis indicates 47.7% CDDT conversion. The weight selectivity of the C12 components are: 32.7g n- butyl ester of 12-oxo-dodeca-4,8-dieneoic acid, 0.4g dodeca-4 _; 8-diene-l,12-dialdehyde and 0.6g 12-oxo-dodeca-4,8-dieneoic acid. The non-selective products are: 0.2g unsaturated C _g dialdehyde, 0.7g unsaturated n-butyl ester of C _& aldehydic acid, 0.6g unsaturated n-butyl diester of Cg diacid and 0.5g of combined C ₄ impurities. 31.4g of CDDT fed is unconverted in this example. The normalized molar selectivity of the reacted CDDT is 90.2% for n-butyl ester of 12-oxo-dodeca-4,8-dieneoic acid, 1.6% for Dodeca-4,8-diene-l,12-dialdehyde, 2.0% for 12-oxo- dodeca-4,8-dieneoic acid, 3.5% for combined C ₈ 's and 0.7% for combined C ₄ "s. The overall preservation of the C ₁₂ species is calculated to be 94% on a normalized basis with the remaining 6% non-selectively cleaved molecules from the ozone attack on second double bond, e.g., Cg's and the corresponding C4 S.

[00228] 12-Oxo-dodeca-4,8-dienoic acid, n-butyl ester, major product in Example 1 :

[00229] ^! H NMR (CDC1 ₃ , 400MHz): 6 _H 9.75 (1H, s, ¾), 5.32 (1H, t, H ₄ ), 5.32 (1H, t, ¾), 5.32 (1H, t, ¾), 5.32 (1H, t, H ₉ ), 4.15 (2H, t, H ₁₃ ), 2.36 (2H, m, H ₂ ), 2.36 (2H, m, H ₁₀ ), 2.36 (2H, m, H _n ), 2.15 (2H, ra, H ₃ ), 2.07 (2H, m, ¾), 2.07 (2H, m, H ₇ ), 21.58 (2H, m, H ₁₄ ), 1.35 (2H, m, His), 0.96 (3H, t, Hi ₆ ). ^I3 C NMR (CDC1 ₃ , 125MHz): δ ₀ 202.5 (s, C _i2 ) _; 173.4 (s, d), 129.8 (s, C ₄ ), 129.8 (s, C ₅ ), 128.4 (s, C _g ), 128.4 (s, C ₉ ), 64.2 (s, C ₁₃ ), 44.9 (s, C ₂ ), 31.8 (s, C ₆ ), 31,8 (s ,C ₇ ), 31.8 (s, Cn), 30.6 (s, C ₁₀ ), 28.4 (s, C ₃ ), 30.6 (s, C ₁₄ ), 19.3 (s, C ₁₅ ), 13.9 (s, C ₁₆ ).

[00230] Examples 2-5: are conducted analogous to Example 1 with the reaction temperature variation in the 5 °C to 40 °C range as identified in Table 2.

Table 2 - 60g CDDT, 35.2g acetic anhydride / 7.5g triethylamine

[00231] Examples 6-9: are conducted analogous to Example 1 with parameter variations as identified in Table 3. Table 3 - 0.078 g/min ozone, 21% 0 ₂ in Argon gas used for ozone, 5 °C temperature

[00232] Example 10: Employing the reactor and procedure described in Example 1, a steady concentration of 26 Ag ozone/m ³ in 3 liter/min argon flow is sparged into the reaction vessel for 92 minutes containing 48g (0.30 mole) of CDDT and 32g of fresh, dry n-butyl alcohol. The reaction is carried out at 35.0°C bulk temperature. When the reaction is complete, excess alcohol is flashed off at 50°C and under vacuum. To the concentrated reaction intermediate a cooled liquid mixture of 28g acetic anhydride and freshly prepared, catalytic mixture of 8,9g triethylamine in 16. lg acetic acid is added via pump with 650 RPM stirring of the reaction mixture. The reaction exotherms, observed during these additions, are managed by active jacketed cooling to ensure the temperature is maintained at or below 40°C. The reaction mixture is allowed to reach room temperature and stirred for additional time for reaction completion. 105g of one-phase liquid reaction product is recovered. The final GC analysis indicates 51.6% CDDT conversion. The weight selectivity of the C ₁₂ components are: 24.4g n-butyl ester of 12- oxo-dodeca-4,8-dieneoic acid, 0.3g dodeca-4,8-diene-l,12-dialdehyde and 0.5g 12-oxo-dodeca- 4,8-dieneoic acid. The non-selective products are: 0.2g unsaturated C ₈ dialdehyde, 0.7g unsaturated n-butyl ester of C8 aldehydic acid, 0.5g unsaturated n-butyl diester of C8 diacid and 0.5g of combined C ₄ impurities. 23.2g of CDDT fed is unconverted in this example. The normalized molar selectivity of the reacted CDDT is 88.4% for n-butyl ester of 12-oxo-dodeca- 4,8-dieneoic acid, 1.2% for dodeca-4 _J 8-diene-l _J 12-dialdehyde, 2.5% for 12-oxo-dodeca-4,8- dieneoic acid, 3.4% for combined C8's and 0.7% for combined C4's. The overall preservation of the C12 species is calculated to be 92% on a normalized basis with the remaining 8% non- selectively cleaved molecules from the ozone attack on second double bond, e.g., Cg's and the corresponding C ₄ 's.

[00233] Examples 11 and 12: are conducted analogous to Example 10 with parameter variations as identified in Table 4. Table 4 0.078 g/min ozone, 21% O2 in Argon gas used for ozone

[00234] Comparative Example 13 (excess reagent is not stripped after ozonolysis):

Employing the reactor and procedure described in Example 1, a steady concentration of 26,2 g ozone/m ³ in 3 liter/min argon flow is sparged into the reaction vessel for 143 minutes containing 75g (0.46 mole) of CDDT and 26.7g of fresh, dry n-butyl alcohol. The reaction is carried out at 5.0°C bulk temperature. When the reaction is complete a cooled liquid mixture of 60g acetic anhydride and 16.7g of triethyl amine is added at a feed rate of 2 g/min via pump with 650 RPM stilling of the reaction mixture. The reaction exotherms, observed during these additions, are managed by active jacketed cooling to ensure the temperature is maintained at or below 10°C. The reaction mixture is allowed to reach room temperature and stirred for additional 30 minutes for reaction completion. 179g of one-phase liquid reaction product is recovered. The GC confirms that the reaction product contains about 5 wt% of alcohol. The final GC analysis indicates 44% CDDT conversion. The weight selectivity of the C ₁₂ components are: 36.8g n- butyl ester of 12-oxo-dodeca-4,8-dieneoic acid, 0.8g dodeca-4,8-diene-l,12-dialdehyde and 1.2g 12-oxo-dodeca-4,8-dieneoic acid. The non-selective products are: 0.6g unsaturated Cg dialdehyde, 0.9g unsaturated n-butyl ester of C8 aldehydic acid, 0.7g unsaturated n-butyl diester of C ₈ diacid and 1.3g of combined C ₄ impurities. 41.7g of CDDT fed is unconverted in this example. The normalized molar selectivity of the reacted CDDT is 84% for n-butyl ester of 12- oxo-dodeca-4,8-dieneoic acid, 2.6% for dodeca-4,8-diene-l,12-dialdehyde, 3.5% for 12-oxo- dodeca-4,8-dieneoic acid, 7.5% for combined C ₈ 's and 2.3% for combined C ₄ 's. The overall preservation of the C ₁₂ species is calculated to be 90% on a normalized basis with the remaining 10% non-selectively cleaved molecules from the ozone attack on second double bond, e.g., Cg's and the corresponding C ₄ 's. The equilibrated azeotropes are present in the effluent as evidenced by the GC analysis. The effluent is combined with the other effluents from similar experiments and is further processed. It is found that the separations are very difficult between the targeted product and the azeotropic complexes containing butyl acetate and other low boiling components.

[00235] Example 14: The thermal stability of three different intermediates generated from the ozonolysis of CDDT is investigated using the standard-cell DSC experiments. The three different ozonolysis intermediates used are; (A) the compound of formula Ila: , obtained from the ozonolysis of CDDT in the presence of methanol, wherein R ¹ is methyl, R ³ is an aldehyde, and A is a C ₁₀ alkene chain with two double bonds;

(B) the compound of formula Ila, obtained from the ozonolysis of CDDT in the presence of 1-propanol, wherein R ³ is 1 -propyl, R ³ is an aldehyde, and A is a Cj ₀ alkene chain with two double bonds; and

(C) the compound of formula Ila, obtained from the ozonolysis of CDDT in the presence of n-butanol, wherein R ¹ is 1 -butyl, R ³ is an aldehyde, and A is a C ₁₀ alkene chain with two double bonds.

[00236] In the DSC experiment, each sample is first equilibrated at 20°C for 1.0 min. The equilibrated sample temperature is then ramped at the 10.0°C/min rate to the target temperature of 220.0°C. The sample is maintained at the target temperature for 1.0 min before completing the first cycle via cool-down to 20°C. FIG. 3 shows the DSC-measured heat flow activity on the Y-axis with respect to the sample temperature on the X-axis for the three intermediates tested in this example. The onset of heat flow (in watts/gram) from each of the three samples is at least after 80°C, more like at the 90°C mark on the X-axis. The DSC data provides sufficient confirmation of the thermal stability of the three intermediates disclosed herein.

[00237] Example 14 intermediate B (12-propoxy-12-hydroperoxy-dodeca-4,8-dienaI):

1H NMR (CDC1 ₃ , 400ΜΗζ):δ _Η 9.75 (1H, s, ¾), 5.32 (1H, t, ¾), 5.32 (1H, t, ¾), 5.32 (1H, t, ¾), 5.32 (1H, t, H ₉ ), 5.37 (1H, t, H ₁₂ ), 4.14 (2H, t, H ₁₃ ), 2.36 (2H, m, H ₂ ), 2.15 (2H, m, ¾), 2.07 (2H, m, H ₆ ), 2.07 (2H, m, H ₇ ), 2.05 (2H, m, H _!0 ), 1.62 (2H, m, Hu), 1.65 (2H, m, H _i4 ), 0.99 (3H, t, H15). ¹³ C NMR (CDC1 ₃ , 125MHz): d _c 202.5 (s, d), 129.8 (s, C ₄ ), 129.8 (s, C ₅ ), 128.4 (s, C ₈ ), 128,4 (s, C ₉ ), 107.3 (s, C ₁₂ ), 68.2 (s, C ₁₃ ), 43.7 (s, C ₂ ), 35.6 (s, C _i4 ), 31.8 (s, C ₆ ), 31.8 (s, C ₇ ), 30.8 (s, di), 28.4 (s, C ₃ ), 28.4 (s, C _i0 ), 28.4 (s, C _M ), 10.3 (s, C, ₅ ).

{00238] Example 14 intermediate C (12-butoxy-12-hydiOperoxy-dodeca-4,8-dienal):

Ή NMR (CDC1 ₃ , 400ΜΗζ):δ _Η 9.75 (1H, s, ¾), 5.37 (2H, 1H, t, H ₁₂ ), 5.32 (1H, t, H ₄ ), 5.32 (1H, t, H ₅ ), 5.32 (1H, t, ¾), 5.32 (1H, t, H ₉ ), 4.15 (2H, t, H _i3 ), 2.36 (2H, m, H ₂ ), 2.15 (2H, m, ¾), 2.07 (2H, m, H ₆ ), 2.07. (2H, m, H ₇ ), 2.05 (2H, m, H _i0 ) ₅ 1.62 (2H, m, H _u ), 1.42 (2H, m, H ₁₄ ), 1.42 (2h, m, His), 0.96 (3H _} t, H ₁₆ ). 13C NMR (CDC1 _3} 125MHz): 5 _C 202.5 (s, d), 129.8 (s, C ₄ ), 129.8 (s, C ₅ ), 128.4 (s, C ₈ ), 128.4 (s, C ₉ ), 107.3 (s, C ₁₂ ), 64.2 (s, C ₁₃ ), 44.9 (s, C ₂ ), 31.8 (s, C ₆ ), 31.8 (s ,C ₇ ) _} 31.8 (s, C„) ₅ 30.6 (s, Cio), 30.6 (s, C ₁₄ ), 28.4 (s, C ₃ ), 19.3 (s, C ₁₅ ), 13.9 (s, C ₁₆ ).

[00239] Example 15: The DSC conditions of Example 14 are re-run for an additional

intermediate D, the compound of formula lib: wherein R ¹ is 1 -butyl, R ² is an acetyl group, R ³ is an aldehyde, and A is a Ci ₀ all ene chain with two double bonds. The intermediate D is obtained from the intermediate C of Example 14 via catalytic transformation according to this invention. In FIG. 4, the solid-lined data refers to Intermediate C in Example 14, and the dash-lined data refers to the catalytic transformation intermediate D disclosed herewith.

[00240] Example 14 provides sufficient evidence of the thermal stability of the intermediates A through C as obtained according to the disclosed process. The significant DSC heat flow activity for ail three analogs is recorded after the sample temperature of 80°C in FIG.4. The Example 14 Intermediate A shows the largest peak for heat flow activity [measure of exothermicity] in comparison with the other two intermediates B and C that show a similar heat flow activity level. The disclosed process recognizes this fact, for the first time, and takes advantage of this important discovery during the effective removal of excess reagent while not exceeding this temperature limit. The carefully chosen and controlled conditions have facilitated in removing the excess reagent without thermal degradation of the compound of formula Ila. The removal of excess reagent before the catalytic transformation minimizes azeotropic formation that is cost- prohibitive to separate, as the disclosed process has discovered.

[00241] Example 15 further shows the thermal stability of intermediate D for temperatures below 60°C and compares with its pre-cursor, intermediate C, from Example 14. The DSC data therefore obtains the operating conditions for the process before compromising the reaction products which may otherwise thermally degrade.

[00242] Example 15 Intermediate D (12-butoxy-12-acetylperoxy-dodeca-4 ₅ 8-dienal):

1H NMR (CDCI3, 400ΜΗζ):δ _Η 9.75 (1H, s, Hi), 5.37 (2H, 1H, t, H ₁₂ ), 5.32 (1H, t, ¾), 5.32 (1H, t, Hs), 5.32 (1H, t, ¾), 5.32 (1H, t, H ₉ ), 4.15 (2H, t, Ho), 2.36 (2H, m, ¾), 2.20 (3H, s, acetylperoxy-CHs), 2.15 (2H, m, H ₃ ), 2.07 (2H, m, H ₆ ), 2.07 (2H, m, H ₇ ), 2.05 (2H, m, H ₁₀ ), 1.62 (2H, m, H _n ), 1.42 (2H, m, H _M ), 1.42 (2H, m, His), 0.96 (3H, t, Hi ₆ ). °C NMR (CDC1 ₃ , 125MHz): 5 _C 202.5 (s, C , 169.4 (s, acetylperoxy-C=0), 129.8 (s, C ₄ ), 129.8 (s, C ₅ ), 128.4 (s, C ₉ ), 128.4 (s, Cio), 107.3 (s, C ₁₂ ), 64.2 (s, C ₁₃ ), 44.9 (s, C ₂ ), 31.8 (s, C ₆ ), 31.8 (s ,C ₇ ), 31.8 (s, C ₈ ), 30.6 (s, C,i), 30.6 (s, C _M ), 28.4 (s, C ₃ ), 22.0 (s, acetylperoxy-CH ₃ ), 19.3 (s, C ₁₅ ), 13.7 (s, Cie).

[00243] 12-Propoxy-12-acetylperoxy-dodeca-4,8-dienal [Example 15 intermediate D wherein R ¹ is 1 -propyl]

1H NMR (CDC1 ₃ , 400ΜΗζ):δ _Η 9.75 (Hi, s, Hi), 5.37 (2H, 1H, t, H _i2 ), 5.32 (1H, t, ¾), 5.32 (1H, t, ¾), 5.32 (1H, t, H ₄ ), 5.32 (1H, t, H ₅ ), ), 4.15 (2H, t, H ₁₃ ), 2.36 (2H, m, ¾), 2.15 (2H, m, H ₃ ), 2.07 (2H, m, ¾), 2.07 (2H, m, H ₇ ), 2.05 (2H, m, H ₁₀ ), 2.20(s, 3H, acetylperoxy-CH ₃ ), 1.62 (2H, m, H111.65 (2h, m, H _]4 ), 0.99 (3H, t, H ₁₅ ). ¹³ C NMR (CDCl _3i 125MHz): 6 _C 202.5 (s, Ci), 169.5 (s, acetyIperoxy-C=0), 129.8 (s, C ₄ ), 129.8 (s, C ₅ ), 128.4 (s, Q), 128.4 (s, C ₉ ), 107.3 (s, C ₁₂ ), 68.2 (s, C13), 43.7 (s, C ₂ ), 35.6 (s, C ₁₄ ), 31.8 (s, C ₆ ), 31.8 (s, C ₇ ), 30.8 (s, C„). 28.4 (s, C ₃ ), 28.4 (s, do), 28.4 (s, C ₁₄ ), 22.0 (s, acetylperoxy-CH ₃ ), 10.3 (s, C ₁₅ ).

[00244] Example 16: Employing the reactor and procedure described in Example 1, a steady concentration of 26.2g ozone/m ³ in 1 liter/min argon flow is sparged into the reaction vessel for 225 minutes containing 35g (0.22 mole) of 1,5,9-cyclododecatriene (CDDT), 15g acetic acid. The reaction is carried out at 5.0°C bulk temperature. When the reaction is complete, the top layer is removed and 2g of sodium acetate dissolved in 9g of acetic acid is added to the bottom reaction mixture in small increments with 650 RPM stirring of the reaction mixture. The reaction exotherms, observed during these additions, are managed by active jacketed cooling to ensure the temperature never exceeds 10°C. The reaction mixture is allowed to warm to room temperature and stirred for an additional two hours. The final GC analysis indicates 64.7% CDDT conversion and normalized product selectivity distribution of 96.7% to the C12 dialdehyde, 1.4% to the C ₁₂ oxo acid, 0.8% to the diacid and 1.1% to the C ₈ dialdehyde is obtained.

[00245] Example 17: A 125ml jacketed reactor vessel is fitted with a dry ice condenser, mechanical stirrer, stainless steel feed tube for sub-surface ozone gas addition and a fourth port for addition of reagents, sampling and thermocouple connection. A premixed oxygen-in-argon gas is fed to an ozone generator (Pacific Ozone). The exit gas from the ozone generator is flowed through an ozone monitor (Teledyne Instruments) for 30min to observe stable ozone concentration in the feed gas. The reaction temperature is maintained at a desired target via jacketed cooling. The exit gas containing residual oxygen and nitrogen are passed through an ice water cold trap to recover any volatile solvent. Upon reaction time completion, dry nitrogen is passed into the reactor for 30min to displace any residual ozone and oxygen and the vessel is warmed to room temperature. CDDT as referenced in Example 1 is used herein.

[00246] A steady concentration of 33.3 g ozone/m in 1 liter/min argon flow (0.033 g ozone/min) is sparged into the reaction vessel for 89 minutes containing lOg (0.06 mole) of CDDT, 4.7g methanol and 56g methyl acetate. Total of 2.97g of ozone is fed to the reaction to achieve a CDDT/ozone molar ratio of about one. The reaction is carried out at 5°C bulk temperature. Upon completion of ozonolysis reaction, the reaction mixture is warmed to 10°C and 3g of Molecular Sieve 4 A is slowly added to the reaction mixture while stirring to maintain below 15°C. Next, 3g of triethylamine is slowly added to the reaction mixture. The reaction mixture is allowed to warm to room temperature and stirred for 30 minutes. Reaction product is recovered as a single phase (63.2g + 2.8g in cold trap). The final GC analysis indicates 69.2% CDDT conversion. About 3.1g of CDDT remains unconverted. The GC-analyzed, solvent-free, product distribution is 3.1g Ci ₂ dialdehyde, 1.4g C ₁₂ aldehyde acid, 1.3g methyl ester of C _\2 aldehyde acid, 0.12g C ₈ 's and about lg of not identified by-products.

[00247] Example 18: Employing the reactor and procedure described in Example 17, a steady concentration of 33.1 g ozone/m3 in 1 liter/min argon flow (0.033g ozone/min) is sparged into the reaction vessel for 89 minutes containing lOg (0.06 mole) of CDDT, 4.7g methanol and 56g methyl acetate. Total of 2.96g of ozone is fed to the reaction to achieve a CDDT/ozone molar ratio of about one. The reaction is carried out at 5°C bulk temperature. Upon completion of ozonolysis reaction, the reaction mixture is warmed to 10°C and 5g of dry silica gel is slowly added to the reaction mixture while stirring to maintain below 15°C. Next, 3g of triethylamine is slowly added to the reaction mixture. The reaction mixture is allowed to warm to room temperature and stiixed for 30 minutes. Reaction product is recovered as a single phase (52.3g + 4g in cold trap). The final GC analysis indicates 64.4% CDDT conversion. About 3.6g of CDDT remains unconverted. The GC-analyzed, solvent- free, product distribution is 4.1g Cn dialdehyde, 2.3g Ci ₂ aldehyde ester, 0.6g C ₈ 's and about 1.4g of not identified by-products. [00248] Example 19: The XUS 43568, Amberlyst ^{1 M} A21 and Amberlyst ^M A26 OH materials are obtained from Dow Chemicals. The MCM-41 and PSU Cat A are obtained from the Pennsylvania State University. The SBA-15 material is obtained from ACS Materials, LLC. The Zeolyte CBVIOO material is obtained from Zeolyst International.

[00249] Employing the reactor and procedure described in Example 1, a steady concentration

3 ■

of 26.2g ozone/m in 2 liter/min argon flow (0.052g ozone/min) is sparged into the reaction vessel for 123 minutes containing 35g (0,22 mole) of CDDT and 50g n-butanol. Total of 6.45g of ozone is fed to the reaction to achieve a CDDT/ozone molar ratio of about 1.61. The reaction is carried out at 5°C bulk temperature. Total ozono lysis effluent recovered is 85.7g (+4.2g in cold traps). Upon completion of ozonolysis reaction, nine 8g aliquots are sequentially removed from the reaction vessel and placed in small bottles, each equipped with a thermocouple and stir bar. Each aliquot bottle is placed in a wet ice bath for temperature control. The heterogeneous catalysts (~0.6g each) either resin or powder is slowly added to the bottle to observe any reaction exotherm. If not, the bottle is warmed to room temperature (~20°C) and stirred for 30 minutes. For the two bottles [B#8, B#9] with triethylamine, the amine is added second. The following eleven sample bottles (B#l-9 + B#10 as control + B#ll as B#l re-treated) are such prepared:

- Heterogeneous Catalysts

Table 6 Summary of the Conversion, Selectivity and Carbon Preservation Results of Example 19

[00250] Example 20 (Preparation of 8-oxo-octa-4-eneoic acid butyl ester): A SOOmL jacketed reactor is charged with 35g (0.32 mole) 1,5-cyclcooctadiene and 65g (0.88 mole) 1-butanol. A flow of 21% 0 ₂ in Argon is fed to the ozone generator followed by flowing to an ozone monitor. A flow of 2 1pm is set on the ozone generator that flowed to the ozone monitor. A steady state (20-30min) concentration of 33g ozone/m ³ in Argon is measured continuously on the monitor. After ~ 15min at steady state, the feed ozone in Argon is diverted to the reactor. The jacketed reactor containing, a mechanical stin'er, a tube for the ozone addition, an exit gas fitting and a fourth port for addition of reagents and sampling with a thermocouple is maintained at minus 5°C. The coolant from the circulating bath (13 liters, 15 liter/min) is circulated through the vessel. The gas is flowed through the reactor followed by passing through a Dry Ice cold trap followed by a scrubber containing 66g tetradecane. The ozone monitor continually measured the ozone concentration fed during the run. The run time is 141min. The ozone generator is then turned off and nitrogen is then passed into the reactor for 5 min to remove any residual ozone.

[00251] When the reaction is complete, un-reacted 1-butanol is removed under high vacuum at < 50 ^° C (max) and ~ 462-472 mtorr. The reactor is warmed to 25 ^° C followed by the addition of 32g (0.31 mole) acetic anhydride and run for 15min. Triethylamine (12g, 0.12 mole) is next added < 25 C. After the complete addition the reaction is run for 120min. The conversion of 1,5-cyclooctadiene is 81% (92% accounted for with the remaining lost in the off gas). Selectivity to 8-oxo-octa-4-eneoic acid butyl ester is 84.1% along with selectivities of 7.5%, 6.1% and 3.1%» to 4-oxo-succinic acid butyl ester, dibutyl succinate and 1,8-octadial, respectively.

[00252] Example 21 (Preparation of 12-oxo-dodecanoic acid methyl ester): Cyclododecene (CAS No. 1501-82-2) is obtained from Alfa Aesar (A Johnson Matthey Company). The purity of Cyclododecene is 97 wt%. Employing the 500ml reactor and procedure of Example 1, a steady concentration of 26.7g ozone/m3 in 2 liter/min argon flow is sparged into the reaction vessel for 95 minutes containing 15.8g (0.10 mole) of cyclododecene, 7g methanol and 90g methyl acetate. The reaction is carried out at 4.4°C bulk temperature. 5.1g (0.11 mole) of total ozone is fed to the reaction mixture. When the reaction is complete, a cooled liquid mixture of 30g acetic anhydride and 8g triethylamine is added via pump at an average feed rate of 2.11 g/min with 650 RPM Stirling of the reaction mixture. The reaction exo therms, observed during these additions, are managed by active jacketed cooling to ensure the temperature is maintained at or below 20°C. The reaction mixture is allowed to reach room temperature and stirred for additional 30 minutes for completion. 127.3g of one-phase liquid reaction product is recovered plus 17.4g of liquid is recovered from the dry ice condenser. The final GC analysis indicates 99.6% cyclododecene conversion. The weight selectivity of the C ₁₂ components are: 16.2g methyl ester of 12-oxo-dodecanoic acid, 1.8g 1,12-dodecanedialdehyde, O.lg cyclododecene and 4.4g of combined unidentified byproducts. The normalized molar selectivity of the reacted cyclododecene is 67.4% for methyl ester of 12-oxo-dodecanoic acid, 8.8% for 1,12- dodecanedialdehyde and 23.8%) combined unidentified byproducts, Fig. 5 is a representation of

Example 21, wherein B is a do alkylene chain, is methyl, and R is an aldehyde in the compound of formula IV.

[00253] Example 22 (Preparation of 12-oxo-dodecanoic acid butyl ester): Employing the reactor and procedure of Example 1 and the cyclododecene described in Example 21, a steady concentration of 26.2g ozone/m ³ is sparged sub-surface into the reaction vessel containing a liquid mixture of 45g (0.27 mole) of cyclododecene and 60g (0.81 mole) of n-butyl alcohol that is dried over the molecular sieves. The total ozone fed is 15.0g at the 0.10 g/min feed rate, which is equivalent to the molar feed ratio of 1.15 ozone/ cyclododecene. The reaction is carried out at 5°C bulk temperature for 150 minutes. When the reaction is complete, a cooled liquid mixture of 55g ACAN and 8.3g Et N is added to the well-agitated reaction intermediate. The reaction exotherms, observed during these additions, are managed by active jacketed cooling to ensure the temperature is maintained at or below 10°C. The reaction mixture is allowed to reach room temperature and stirred for additional 30 minutes for completion, 168g of one-phase liquid reaction product is recovered. The final GC analysis indicates complete conversion of cyclododecene. The major products are: butyl ester of 12-oxo-dodecanoic acid, 1,12- dodecanedialdehyde, <0.1g cyclododecene plus unidentified byproducts. Fig. 5 is a representation of Example 22, wherein B is a Cio alkylene chain, R ¹ is n-butyl, and R ³ is an aldehyde in the compound of formula JV.

[00254] Example 23 (Preparation of 8-oxo-octanoic acid butyl ester): A 95wt% min. purity cis-cyclooctene (CAS No. 931-87-3) is purchased from Sigma Aldrich. Employing the reactor and procedure similar to Example 21, ozonolysis of cyclooctene in the presence of dry n-butanol followed by its transformation with ACAN and Et ₃ N produces n-butyl ester of 8-oxo-octanoic acid in almost quantitative yield. The cyclooctene conversion in complete within 120 minutes and at 5°C reaction temperature. Fig. 5 is a representation of Example 23, wherein B is a C ₆ alkylene chain, R ¹ is n-butyl, and R ³ is an aldehyde in the compound of formula IV.

[002SS] Example 24 (Preparation of 1,12-dioxo-dodecane): Employing the reactor, procedure and cyclododecene described in Example 21, a steady concentration of 26.2g ozone/m ³ in bulk argon flow is sparged into the reaction vessel for about 150 minutes containing 35g (0.21 mole) of cyclododecene and 30g acetic acid. The reaction is carried out at 5.0°C bulk temperature. When the reaction is complete, the top layer is removed and 4g of sodium acetate dissolved in 18g of acetic acid is added to the bottom reaction mixture in small increments with 650 RPM stirring of the reaction mixture. The reaction exotherms, observed during these additions, are managed by active jacketed cooling to ensure the temperature never exceeds 10°C. The reaction mixture is allowed to warm to room temperature and stirred for an additional two hours. The final GC analysis indicates complete cyclododecene conversion with 1,12-dioxo-dodecane as a major product in high yield. [00256] Example 25 (Preparation of 1,8-octanedialdehyde): The reactor, procedure and cyclooctene described in Example 23 are used. The reactor is charged with 15g cyclooctene, 80g methyl acetate and 48g DI water. A flow of 21% 0 ₂ in Argon is fed to the ozone generator followed by flowing to an ozone monitor, A steady state (20-30min) concentration of 33.0g ozone/m ³ in bulk Argon gas is measured continuously on the monitor. After about 15min at steady state, the feed ozone in Argon is fed to the reactor. The jacketed reactor containing, a mechanical stirrer, a tube for the ozone addition, an exit gas fitting and a fourth port for addition of reagents and sampling and TC is maintained at 5°C. The coolant from the circulating bath (13 liters, 151iter/min) is circulated through the vessel. The gas is flowed through the reactor followed by passing through a Dry Ice cold trap, a scrubber containing 66g tetradecane followed by a KI scrubbing solution. The ozone monitor continually measures the ozone concentration during the run. Run time is 175min. The ozone generator is then turned off and nitrogen is then passed into the reactor for 5 min to remove any residual ozone.

[00257] The reaction produces two layers with satisfactory mass balances. Some C ₈ products are observed in the top aqueous/methyl acetate layer. The bottom layer is enriched in 1,8- octanedialdehyde. Both layers contain ¾(¾, a co-product from dialdehyde production. The 3¾0 ₂ is destroyed with 10% aqueous a ₂ S ₂ 03. The conversion of cyclooctene is complete by GC measurement.

[00258] Example 26 (Preparation of 1,12-dodecanediamine): A 125cc Hastelloy C metal autoclave, equipped with an agitator, heat exchange jacket, bulk liquid thermocouple and inert nitrogen purge, is used for catalytic reductive amination. A solution of lOg 1,12-dioxo-dodecane (prepared according to Example 24) in 50g isopropanol is charged to the autoclave at 10°C. To the feed in the autoclave is slowly added 30g of 28% aqueous NH ₄ OH (temperature rise is noted). Raney ^® Ni (3.0g, Raney ^® 3111) is next added. The autoclave is sealed and pressure tested at 200psig. After the pressure test, the temperature is raised to 60°C and run at 600psig with 900 RPM stirring. The run time is determined by hydrogen uptake and/or disappearance of starting oxo or imine as measured by LC. The reaction mixture is sampled with time to determine the extent of conversion. After the run, the autoclave is depressurized slowly at 20°C to remove most of the ammonia and the product and catalyst are removed under N ₂ into a tared bottle. The catalyst is filtered from the product under N ₂ and stored in refrigerator. GC analysis shows complete conversion of the 1,12-dioxo-dodecane to the 1,12-dodecanediamine.

[00259] Example 27 (Preparation of 12-oxo-dodecanoic acid): A solution of 15g 1,12-dioxo- dodecane (prepared according to Example 24) in 20g toluene is charged into a 125cc jacketed glass vessel. Mn(OAc) ₂ catalyst (O.lg) is also added to the solution. Air is sparged into the vessel at 500ml/min for 6 hrs at 50°C. GC analysis of the product shows 50% conversion of the 1,12-dioxo-dodecane to both insoluble 12-oxo-dodecanoic acid and 1,12-dodecandioic acid products.

[00260] Example 28 (Preparation of 1,12-dodecanediol): About 5g 1,12-dioxo-dodecane (prepared according to Example 24) in about 43 g isopropanol is charged to the autoclave described in Example 26 at 15 °C. The autoclave is pressure tested at SOOpsig with slow stirring. The residual nitrogen is removed with two purges of 200psig hydrogen without stirring at 15°C. The autoclave is warmed to 45°C and 900 RPM and stirring commences at 400psig. The hydrogenation is run for 3hrs followed by depressurization to the ambient pressure and nitrogen purging. The product is filtered through Celite filter aid under vacuum to recover approximately 41.7g solution and 8.9g rinse. GC analysis shows complete conversion of 1,12-dioxo-dodecane to 1,12-dodecanediol in 90% yield.