l-Mβthyl-2-oxaallcoxy-Derivatives

The invention relates to the use of l-methyl-2-oxaalkoxy derivatives of the formula I

Ri-(- A Vz) _o - B Vcθ-0- 0 Vo-CH(CH ₃ )-CH ₂ -0-Q-R2 I

0- ^~ - ) _m

wherein

R ¹ and R ² are each independently a normal or branched alkyl residue with up to 16 C atoms or a normal or branched alkenyl residue with 3 to 16 C atoms wherein one or two non-adjecent CH ₂ groups of these residues may be replaced by -0-, -CO-, -O-CO- or -CO-0-,

and

"Vv ^{~ and} _\ ___y ^{are each} independently a 1,4-phenylene group optionally substituted by up to 4 methyl groups or halogen atoms, in which one or two CH groups may be replaced by N, or a trans- 1, -cyclohexylene group, in which one or two non-adjacent CH ₂ groups may be replaced by

-0- or -S-, or a l,4-bicyclo[2.2.2]octylene group.

Z is -CH ₂ 0-, -OCH ₂ -, -CO-O-, -0-CO-, CH ₂ CH ₂ -,

-C ^~~ C- or a single bond,

Q is CH ₂ or CO,

5

X ¹ is a methyl group or an halogen atom,

is 0, 1, 2 ^" , 3 or 4 and

0 o is 0, 1 or 2,

as components of thermochromic liquid crystalline composi¬ tions.

^~ -5 Liquid crystal phases are exhibited by certain organic com¬ pounds and constitute an intermediate state which exists between the crystalline solid and the fully disordered liquid phase and within which certain long range ordering of the molecules takes place. 20

There are two broad types of liquid crystal phase; the smec- tic mesophase in which the long range ordering is of a sub¬ stantially lamellar type and the nematic mesophase in which the ordering is substantially linear, i.e. the molecules tend

25 to line up with the long axes of the molecules parallel.

Included sometimes as a subclass of the nematic mesophase and sometimes classified as a separate mesophase is the choles- teric mesophase. This last has a helical long range order imposed upon the linear order of the nematic mesophase.

- ^** "*- ¹ Compounds displaying a cholesteric mesophase are optically

active (chiral) and the pitch of the helical twist is deter¬ mined by the nature and extent of the optical activity. The pitch of the helical twist may be such that thin films of the cholesteric phase reflect visible light, resulting in the observation of bright colors, and the pitch may also be sharply temperature dependent resulting in the reflection of particular color over particular temperature ranges so that the cholesteric mesophase in question can act as a "thermo¬ meter" . This behavior is known as thermochromism.

The chiral compounds of the formula I exhibit, as a rule, a cholesteric mesophase (hereinafter designated Ch) because of their molecular shape and optical activity and also a chiral smectic A mesophase (hereinafter designated S _A ) underlying the cholesteric mesophase.

Also, above the S _A -Ch transition, the compounds of the present invention exhibit, either on their own or when mixed with one of more other liquid crystal compounds, a cholesteric liquid crystal phase in which the molecules are arranged in the helical formulation of that phase such that a film of the phase in the Grandjean plane texture rotates the plane of polarisation of incident polarised light and reflects ellip- tically polarised light of specific wavelengths when illumi- nated by ordinary light, so that the mesophases are thermo¬ chromic.

The compounds of the present invention have properties such that they may be used in a liquid crystal electrooptic device such as a "phase change" device in which the material is changed between a so-called "focalconic" cholesteric state, which scatters light, and a transparent nematic state by an applied electric field and in accordance with one aspect of the present invention an electrooptic device includes in its liquid crystalline material a compound as hereinbefore defined. It will of course be realised that there may be present, a mixture (solution) of compounds as hereinbefore defined and that other compounds exhibiting liquid crystal¬ line behavior may be included. Preferably the mixture of compounds used is a eutectic. The optical mixture of com¬ pounds used is a eutectic. The optical effect of the electro- optical device may be enhanced by the inclusion of pleochroic dyes. Suitable pleochroic dyes for this purpose are described in UK patent Ser. No. 1,555,954 and No. 1,555,955.

The materials of the present invention and mixtures thereof may thus be used in surface thermography, e.g. for the detec¬ tion of breast cancer. They may be applied in a thin film on the surface of interest. The color of the film in reflection at right angles to the surface indicates the temperature of the surface.

This last mentioned property may be used to produce a temper¬ ature sensitive display device, e.g. a thermometer, giving a visual display resulting from the effect of changes of tem¬ perature upon the helical pitch of the material and conse- quently the reflected color.

The compounds of the formula I are covered in part by a broad formula of the Janpanese Patent Application JO 2 067 252. This document suggest the use of such compounds as chiral dopants of ferroelectric compositions. But the use of such compounds according to the invention is not described there.

No one skilled in the art, therefore, could recognize that the compounds of formula I have high twisting powers which import to thermochronic compositions with bright colors and favorable mesophase ranges and a extraordinarily high stabi¬ lity against light, especially UV.

Similar thermochronic compositions are described in the UK Patent Ser. No. 1,603,076 which discloses chiral biphenyl, cyclohexyl and benzoyloxyphenyl esters of (+)-4-(2'-methyl- butyl)-phenol.

A great disadvantage for many applications of these materials is their low chemical, heat and light, especially UV, stabil¬ ity. Another adverse property of phases based on these com¬ pounds is that high order smectic phases such as, for exam¬ ple. Si, occur at low temperatures, so that the switching time properties are adversely influenced and/or the pitch and/or the tilt and/or the viscosity of the phases do not meet the requirements of display technology.

It has now been found that the compounds of the formula I can substantially reduce the disadvantages mentioned, in particu¬ lar the possibility of racemizing the chiral centre is very clearly reduced.

The compounds of the formula I are thus outstandingly suit¬ able as components of liquid crystal phases, especially of cholesteric phases. In particular cholesteric phases prepared by the aid of these compounds are chemically stable, have favorable viscosity values, and broad Ch phases ranges with¬ out occurrence of high order smectic phases.

The compounds of the formula I have a wide range of applica¬ tions. Depending of the choice of substituents, these com- pounds can be used either as base materials from which liquid crystal cholesteric phases are predominantly composed or as optically active additives which induce the cholesteric phase in a nematic phase, however, it is also possible for com¬ pounds of the formula I to be added to liquid crystal base materials from other classes of compounds, for example, in order to vary the dielectric and/or optical anisotropy and/or the viscosity and/or the phase ranges and/or the tilt angle and/or the pitch of such a dielectric.

The invention thus relates to the use of compounds of the formula I.

Furthermore, the invention relates to a derivative of the formula I wherein o is 1 or 2 and is trans-l,4-cyclo- hexylene.

A further aspect of the invention are derivatives of formula II

^R1 " _\ A " ^(CH 2 _* y> _P θVcθO- θ -0-CH ⁽ CH ₃ )-CH ₂ -0-CH ₂ -R ² II

^{F F} (F) _m

wherein

Ri, R2, - AV, m have the meaning given, p is 0 or 1 and y is O or CH ₂ ,

and

of formula 12

Ri ^l - ⁽ ®0 >"-( ⁽ C ^C H ^H ₂ 2y ^y ) ⁾ _pP --((BB)-CCOOOO--( 09)V--OO--CH(CH ₃ )-CH ₂ -0-CH ₂ -R2 12

wherein

R ¹ ,R ² , L/ ' ⁿ ' P ^{anci y have tlie} meaning given, in particular wherein p has the value 0.

Another subject matter of this invention is a liquid crystal¬ line phase with at least two components, characterized in that at least one component is a compound of the formula I, or of the formulae II or 12.

In the compounds of formula I, wherein - A - is cyclohexy- lene, both the K-Ch and CH-I transitions decrease markedly as the homologous series is ascended; monotropic S _A phases are observed for the first five members of the series. 0

In the compounds of formulae II and 12 the Ch-I and S _A -Ch transitions decrease steadily across the series before both reach a minimum for the butyl homologue and the rise for the pentyl and hexyl homologues; the Ch phase range is largest --$ for the methyl homologue but varies between 22 and 29 °C.

In both the mono-fluoro of formula II and di-fluoro compounds of formula 12 the thermal stability of the S _A phase is reduced and the tendency to form ordered B phases is suppressed.

20

The mono-flouro materials II show increasingly larger reduc¬ tions in clearing points over their non-fluorinated parent compounds; this reduction is not so marked in the di-fluoro compounds 12.

25

The invention relates furthermore to an electrooptic device containing such a liquid crystalline phase and to a tempera¬ ture indicating device containing such a liquid crystalline phase.

30

Eventually the invention relates to a method of surface thermography which includes the step of

(a) applying a thin film of a compound of the formula I or a liquid crystalline phase containing a compound of the formula I to a surface and

(b) observing the color of the film in reflection at angles of 60° to 90° to the surface.

For simplicity, in the following text, R* denotes a chiral l-methyl-2-oxaalkoxy group of formula -0-CH(CH ₃ ) *-CH ₂ -C—Q-R2,

Pha denotes an unsubstitued 1,4-phenylene group, PheX a 1,4-phenylene group substituted by up to four fluorine atoms and Cyc denotes a trans-l,4-cyclohexylene group.

Preferred compounds of the formula I are those of the part formulae la to In:

R ⁱ -Phe-CO-O-Phe-R* la R ⁱ -PheX-CO-O-Phe-R* lb

R ⁱ -Phe-CO-0-PheX-R* Ic

R ⁱ -Phe-Phe-COO-Phe-R* Id

R ⁱ -PheX-Phe-COO-Phe-R* Ie

R ⁱ -Phe-PheX-COO-Phe-R* If Ri-Phe-Phe-COO-PheX-R* Ig

Ri-Cyc-Phe-COO-Phe-R* Ih

R ⁱ -Cyc-PheX-COO-Phe-R* Ii

Ri-Cyc-Phe-COO-PheX-R* Ij

R ^~ -Cyc-Cyc-COO-PheX-R* Ik Ri-Cyc-Cyc-COO-Phe-R* II

Ri-Cyc-CH ₂ 0-Phe-COO-Phe-R* Im

Ri-Cyc-CH ₂ CH ₂ -Phe-COO-Phe-R* In

Preferred are those compounds wherein PheX denotes a 1,4-phenylene group substituted by one or two fluorine atoms. Particularly preferred are compounds wherein PheX denotes a 2-(3-) fluoro-1,4-phenylene group.

If R ¹ and R ² are each an alkyl residue and/or alkoxy residue, this radical can be straight-chain or branched. Preferably, it is straight-chain and has 2, 3, 4, 5, 6 od 7 C atoms and is accordingly preferably ethyl, propyl, butyl, pentyl, hexyl, heptyl, ethoxy, propyloxy, butyloxy, pentyloxy, hexyl- oxy or heptyloxy, also methyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, methoxy, octyloxy, nonyloxy, decyloxy, undecyloxy, dodecyloxy, tridecyloxy or tetradecyloxy.

Oxaalkyl is preferably straight-chain 2-oxapropyl (= methoxy- methyl) , 2-(= ethoxymethyl) or 3-oxabutyl (= 2-methoxy- methyl) , 2-, 3- or 4-oxapentyl, 2-, 3-, 4- or 5-oxahexyl, 2-, 3-, 4-, 5- or 6-oxaheptyl, 2-, 3-, 4-, 5-, 6-, or 7-oxaoctyl, 2-, 3-, 4-, 5-, 6-, 7- or 8-oxanonyl or 2-, 3-, 4-, 5-, 6-, 7-, 8- or 9-oxadecyl.

If R ¹ and R are each an alkyl residue, it can be straight- chain or branched. Preferably, it is straight-chain and has 2 to 10 C atoms. It is accordingly, in particular, vinyl, prop-1- or prop-2-enyl, but-1-, -2- or -3-enyl, pent-1-, -2-, -3- or -4-enyl, hex-1-, -2-, -3-, -4- or -5-enyl, hept-1-, -2-, -3-, -4-, -5- or -6-enyl, oct-1-, -2-, -3-, -4-, -5-, -6-, or -7-enyl, non-1-, -2-, -3-, -4-, -5-, -6-, -7- or -8-enyl or dec-1-, -2-, -3-, -4-, -5-, -6-, -7-, -8- or -9-enyl.

Compounds of the formula I with branched terminal residues Ri and R ² can occasionally be of importance because of an improved solubility in the customary liquid crystal base materials.

Branched groups of this type as a rule contain not more than one chain branching. Preferred branched residues R ¹ and R2 are isopropyl, 2-butyl (= 1-methylpropyl) , isobutyl (= 2-methyl- propyl) , 2-methylbutyl, isopentyl (= 3-methyl-butyl) , 2-methylpentyl, 3-methylpentyl, 2-ethylhexyl, 2-propylpentyl, isopropoxy, 2-methylpropoxy, 2-methylbutoxy, 3-methylbutoxy, 2-methylpentoxy, 3-methylpentoxy, 2-ethylhexoxy, 1-methylhex- oxy and 1-methylheptoxy.

Formula I includes both the racemates of these compounds and the optical antipodes, as well as mixtures thereof.

Those of the compounds of the formulae I, la to In in which at least one of the residue contained therein has one of the preferred meanings mentioned are preferred.

The compounds of the formula I are prepared by methods which are known per se, such as are described in the literature (for example in the standard works, such as Houben- eyl, Methoden der Organischen Chemie [Methods of Organic

Chemistry], Georg-Thieme-Verlag, Stuttgart), and in particu¬ lar under reaction conditions which are known and suitable for the reactions mentioned in more detail here can also be used in this connection.

If desired, the starting substances can also be formed in situ, such that they are not isolated from the reaction mixture but are immediately reacted further to give the compounds of the formula I.

Esters of the formula I can be obtained by esterification of corresponding carboxylic acids (or their reactive deriva¬ tives) with alcohols or phenols (or their reactive deriva¬ tives) preferably the corresponding carboxylic acid and the alcohol or phenol are reacted with water absorbing means as, for example, mol sieves or carbodiimides, particularly pref¬ erably with dicyclohexylcarbodiimide.

The corresponding carboxylic acids and alcohols or phenols are known or can be prepared by processes analogous to known processes.

Particularly suitable reactive derivatives of the carboxylic acids mentioned are the acid halides, above all the chlorides and bromides, and furthermore the anhydrides, for example also mixed anhydrides, preferably those of the corresponding carboxylic acids and trifluoroacetic acid formed in situ by mixing these carboxylic acids with trifluoroacetic anhydride, acides or esters, in particular alkyl esters with 1-4 C atoms in the alkyl group.

Possible reactive derivatives of the alcohols or phenols mentioned are, in particular, the corresponding metal alcoho- lates or phenolates, preferably of an alkali metal, such as sodium or potassium.

The esterification is advantageously carried out in the presence of an inert solvent. Particularly suitable solvents are ethers, such as diethyl ether, di-n-butyl ether, THF, dioxane or anisole, ketones, such as acetone, butanone or cyclohexanone, amides, such as dimethylformamide or phospho¬ ric acid hexamethyltriamide, hydrocarbons, such as benzene, toluene or xylene, halogenohydrocarbons, such as carbon tetrachloride, dichlormethane or tetrachloroethylene, and sulfoxides, such as dimethylsulfoxide or sulfolane. Water- immiscible solvents can simultaneously be advantageously used for azeotropic distillation of the water formed during the esterification. An excess of an organic base, for example pyridine, quinoline or triethylamine, can occasionally also be used as the solvent for the esterification. An additional, catalytic amount of 4-(N,N-dimethylamino)-pyridine can accel¬ erate the esterification. The esterification can also be carried out in the absence of a solvent, for example by heating the components in the presence of sodium acetate.

The reaction temperature is usually between -50° and +250°, preferable between -20° and +80°. At these temperatures, the esterification reactions have as a rule ended after 15 minutes to 48 hours.

In detail, the reaction conditions for the esterification depend largely on the nature of the starting substances used. Thus, a free carboxylic acid is as a rule reacted with a free alcohol or phenol in the presence of a strong acid, for example a mineral acid, such as hydrochloric acid or sulfuric acid. A preferred reaction procedure is the reaction of an acid anhydride or, in particular, an acid chloride with an alcohol, preferably in a basic medium, bases which are of

importance being, in particular, alkali metal hydroxides, such as sodium hydroxide or potassium hydroxide, alkali metal carbonates or bicarbonates, such as sodium carbonate, sodium bicarbonate, potassium carbonate or potassium bicarbonate, alkali metal acetates, such as sodium acetate or potassium acetate, alkaline earth metal hydroxides, such as calcium hydroxide, or oganic bases, such as triethylamine, pyridine, lutidine, collidine or guinoline. Another preferred embodi¬ ment of the esterification comprises first converting the alcohol or phenol into the sodium alcoholate of phenolate or potassium alcoholate or phenolate, for example by treatment with ethanolic sodium hydroxide solution or potassium hydrox¬ ide solution, isolating this product and suspending it in acetone or diethyl ether, together with sodium bicarbonate or potassium carbonate, with stirring, and adding a solution of the acid chloride or anhydride in diethyl ether, acetone or dimethylformamide to this suspension, advantageously at temperatures between about -25° and +20°.

Alkoxy compounds of the formula I (Cyc-CH ₂ -C—Phe) can be obtained by alkylation of the corresponding phenols (HO-Phe-CO-O-Phe-R*) , the phenol preferably first being converted into a phenolate for example into the alkali con¬ verted into a phenolate for example into the alkali metal phenolate by treatment with NaOH, KOH, Na ₂ C0 ₃ or K ₂ C0 ₃ . This phenolate can then be reacted with the corresponding alkyl halide or sulfonate or dialkylsulfate, preferably in an inert solvent such as acetone, DMF or dimethylsulfoxide or an excess of aqueous or aqueous-alcoholic NaOH or KOH at temper- atures between 0° and 100 °C.

The compounds of formula I are preferably prepared according to the following reaction paths (Schemes I to III) .

Scheme I

a Benzyl bromide, K ₂ C0 ₃ , butanone, reflux b LiAlH ₄ , THF, N ₂ , RT c R ² Br, NaH, DMF, N ₂ , RT d H ₂ , 10 % Pd-C, EtOAc, RT e DCC, DMAP, ^" CH ₂ C1 ₂ , RT

Bn =benzyl, PhCH ₂ -

Schema II

Schcme III

I

Formula II

a = F, b and c ) H

Formula 12

a = H, b and c = F

(i) BuLi, THF, N ₂ , -72 °C; (ii) C0 ₂ (S) , Et ₂ 0, THF, -72 °C to RT b CH ₃ CH ₂ CH ₂ CH ₂ C0C1, A1C1 ₃ , 110-115 °C c H ₂ NNH ₂ • H ₂ 0, KOH, diethylene glycol, heat d (i) BuLi, THF, N ₂ , -72 °C (ii) ( ⁱ PrO) ₃ B, THF, N ₂ , -72 °C to RT (iii) 10 % aq. HC1, RT e Pd (PPh ₃ ) ₄ , 2M-Na ₂ C0 ₃ , dimethoxyethane, N ₂ f DCC, DMAP, CH ₂ C1 ₂ , RT

The liquid crystalline mixtures according to the invention consist of 3 to 25, preferably 4 to 15, components, at least one of which is a compound of the formula I. The other con¬ stituents are preferably chosen from nematic or nematogenic substances, in particular the known substances, from the classes of azoxybenzenes, benzylideneanilines, biphenyls, terphenyls, phenyl or cyclohexyl benzoates, phenyl or cyclo- hexyl cyclohexanecarboxylates, phenylcyclohexanes, cyclo- hexylbiphenyls, cyclohexylcyclohexanes, cyclohexylcyclo- hexenes, cyclohexylnaphthalenes, 1,4-bis-cyclohexylbenzenes, 4,4'-bis-cyclohexylbiphenyls, phenyl- or cyclohexyl- pyrimidines, phenylpyridines, phenyl- or cyclohexyldioxanes, phenyl- or cyclohexyldithianes, 1,2-bis-phenylethanes, 1,2-bis-cyclohexylethanes, l-phenyl-2-cyclohexylethanes, optionally halogenated stilbenes, benzyl phenyl ethers, tolanes and substituted cinnamic acids.

The most important compounds which are possible constituents of such liquid crystalline mixture can be characterized by the formula 1

R3-L-G-E-R4 1

wherein L and E are each an unsubstituted or laterally flouro- or cyano- substituted carbo- or hetero-cyclic ring system from the group comprising 1,4-disubstituted benzene and cyclohexane rings, 1,4-disubstituted 1-cyano-cyclohexane rings, 4, -disubstituted biphenyl, phenylcyclohexane and cyclohexylcyclohexane systems, 2,5-disubstituted naphthalene, di- and tetra-hydronaphthalene, quinazoline and tetrahydro- quinaazoline, G is

-CH=CH- -N (0) =N-

-CH=CY- -CH=N (0) -

-CaC- -CH ₂ -CH ₂ -

-CO-O- -CH ₂ -0-

-CO-S- -CH ₂ -S-

-CH=N- -COO-Phe-COO-

or a C-C single bond, Y is halogen, preferably chlorine, or -CN and R ³ and R ⁴ are alkyl, alkoxy, alkanoyloxy or alkoxy- carbonyloxy with up to 18, preferably up to 8, carbon atoms, it also being possible for one CH ₂ group non-adjacent to an oxygen atom to be replaced by -0-, -CH=CH- or -C≡C-, or that one of the radicals R ³ and R ⁴ may also denote CN, N0 _2/ CF ₃ , NCS, F, Cl or Br.

In most of these compounds, R ³ and R ⁴ are different from one another, one of these radicals usually being an alkyl or alkoxy group. However, other variants of the substituents envisaged can also be used. Many such substances or mixtures thereof are commercially available. All of these substances can be prepared by methods which are known from the litera¬ ture.

The liquid crystalline mixtures according to the invention contain about 0.5 to 100, preferably 15 to 100 %, of one or more compounds of the formula I. Liquid crystalline mixtures which contains 25-100, particular 30-90 %, of one or more compounds of the formula I can be used advantageously in the mixtures according to the invention.

The liquid crystalline mixtures according to the invention are prepared in a manner which is customary per se. As a rule, the corφonents are dissolved in one another, preferably at elevated temperature.

The liquid crystalline mixtures according to the invention can be modified by suitable additives such that they can be used in all the types of liquid crystal display elements disclosed to date.

Such additives are known to the expert and are described in detail in the literature. For example, it is possible to add conductive salts, preferably ethyldimethyldodecylammonium 4-hexyloxybenzoate, tetrabutylammonium tetraphenylboranate or complex salts of crown ethers (compare, for example,

I. Haller et al., Mol. Cryst. Liq. Cryst. Vol. 24., pages 249-258 (1973) ) for improving the conductivity, dichoric dyestuffs for the production of colored guest/host systems or substances for changing the dielectric anisotropy, the vis- cosity and/or the orientation of the nematic phases. Such substances are described, for example, in German Offen- legungsschrift 2,209,127, 2,240,863, 2,321,632, 2,338,281, 2,450,088, 2,637,430, 2,853,728 and 2,902,177.

Preferably the thermochromic mixtures are micro-encapsulated (U.S. Pat. No. 3,584,318) or polymer dispersed (U.S. Pat. No. 1,161,039) .

The thermochromic cholesteric liquid crystals according to the invention are suitable for the thermometry, especially for a good indication of core body temperature in sleeping children and postoperative patients.

Furthermore they can be advantageously applied in the bio- medical thermography as an important diagnostic aid for breast cancer detection or placental location.

Beneath mood indicating jewellery U.S. Pat. 3,802,945 (1979) and nondestructive testing applications they can be used in atmospheric pollutant detection because of the effect of impurities on the selective reflection wavelength of the liquid crystalline mixtures according to the invention.

Furthermore the microencapsulated thermochromic compositions can be used in cosmetic or decorative formulations as, for example, described in WO 90/02054.

The following examples are intended to illustrate the inven¬ tion without limiting it. Percentage above and below are percentages by weight. All the temperatures are given in degrees Centigrade. The symbols are furthermore as follows: K: crystalline solid state, S: smectic phase (the index characterizes the phase type), N: nematic phase, Ch: choles¬ teric phase, I: isotropic phase, B: crystalline B mesophase, BP: blue phase. The figure between two symbols indicates the transition temperature.

Bxample 1

(R)-Benzyl 2-(4-hydroxyphenoxy)propanoate (1A)

(R)-2-(4-Hydroxyphenoxy)propanoic acid (50.00 g, 0.28 mol obtained according EP 0 259 995) was dissolved in methanol- water (500 ml, 9:1) with stirring. The pH was then adjusted to 7.00 (pH meter) using aqueous potassium carbonate (20 % solution) . Most of the solvent was removed under reduced pressure (water pump, water-batch temp. < 50 °C) and the final traces were removed azeotropically using dichloromethane (500 ml) to give a viscous brown oil. This was dissolved in dry DMF (100 ml) and benzyl bromide (47.12 g, 0,28 mol) in dry DMF (65 ml) was added dropwise during 30 min with stir- ring at room temperature. After 48 h, analysis by thin layer chromatography showed that the reaction had reached comple¬ tion and the excess of DMF was then removed under reduced pressure (water pump, water batch at 40-50 °C) and water (200 ml) was added with stirring. The product was extracted into diethyl ether (5 x 40 ml), the extracts were combined and washed with water (3 x 50 ml) , dried (Na ₂ S0 ₄ ) , filtered and the filtrate was evaporated under reduced pressure to give a brown oil. This oil was then purified by column chro¬ matography [silica gel; gradient elution with 9:1 dichloro- methane-petrol (bp 40-60 °C) and finally with 9:1 dichloro- methane-ethyl acetate] to give an oil which crystallized on standing. The product was dried in vacuo (P ₂ O ₅ , 0.30 mmHg, RT, 24 h) .

Yield = 61 . 61 g (82 %) mp 49-51 °C

[a] ^~ = + 31 .7°

Zxample 2

(R)-Benzyl 2-[4-(benzyloxy)phenoxy]propanoate (2A)

Benzyl bromide (12.91 g, 75.50 mmol) in butanone (50 ml) was added dropwise to a mechanically stirred, refluxing suspen¬ sion of compound 1A (20.00 g, 73.75 mmol), potassium carbon¬ ate (11.17 g, 83.23 mmol) and butanone (200 ml). Once the addition was complete the reaction was heated under reflux for 22 h; TLC analysis showed complete reaction. The precipi¬ tated potassium bromide and excess of potassium carbonate was filtered off and the filtrate was evaporated to give a pale oil. The crude product was purified by column chromatography [silica gel; 9:1 dichloromethane-petrol (bp 40-60 °C) ] . The solid obtained was recrystallized [ethyl acetate-petrol (bp 40-60 °C) ] and dried P ₂ 0 ₅ , 0.15 mmHg, RT, 72 h) .

Yield = 22.17 g (83 %) mp 65-66 °C

[α]o = + 21.7°

(R)-2-[4-(Benzyloxy)phenoxy]propan-l-ol (2B)

Compound 2A (22.00 g, 60.77 mmol) in dry tetrahydrofuran

(125 ml) was added dropwise at 0 °C to a stirred suspension of lithium aluminium hydride (2.45 g, 64.56 mmol) in dry tet¬ rahydrofuran (100 ml) whilst under nitrogen. After 3 h at room temperature TLC analysis revealed the absence of start¬ ing material. The excess of lithium aluminium hydride was decomposed by dropwise addition of wet diethyl ether (50 ml) ,

ethyl acetate (50 ml) , water (50 ml) and 10 % (v/v) hydro¬ chloric acid (100 ml) . The product was then extracted into diethyl ether (2 x 100 ml) and the combined extracts were washed with water (50 ml) before being dried (MgS0 ₄ ), filtered and evaporated to give a pale liquid. The crude product was purified by flash chromatography [silica gel; 9:1 dichloro- methane-petrol (bp 40-60 °C) ] and the product was recrystal- lized (ethyl acetate-cyclohexane) and dried in vacuo (P ₂ 0 ₅ ,

0.12 mmHg, 40 °C, 4 h) .

Yield = 14.38 g (91 %) mp 62-66 °C

[a] ^~ = - 32.9°

(R)-2-(4-Benzyloxyphenoxy)-1-methoxypropane (2C)

Compound 2B (2.18 g, 8.45 mmol), methyl iodide (1.22 g, 8.60 mmol) and dry N, -dimethylformamide (20 ml) was added to stirred suspension of sodium hydride (0.80 g, 30 % disper¬ sion, 11 mmol) in dry N,N-dimethylformamide (20 ml) and left to stir at room temperature for 26 h under a nitrogen atmos¬ phere. The excess of sodium hydride was destroyed by cautions addition of water (30 ml) and the reaction mixture was diluted with dichloromethane (30 ml) . The organic phase was then separated and the aqueous phase washed with dichloro- methane (2 x 50 ml) ; the organic extracts were combined and washed successively with water (50 ml) 10 % (v/v) hydro¬ chloric acid (2 x 50 ml) , saturated sodium hydrogen carbonate (2 x 50 ml) and water (50 ml) . The dichloromethane solution

was then dried (MgS0 ₄ ) , filtered and evaporated to give a pale yellow oil which was purified by flash chromatography [fine mesh silica gel; 4 % (v/v) ethyl acetate in petrol (pb 40-60 °C) ] to give a colorless oil which was dried in 5 vacuo (P ₂ 0 ₅ , 0.15 mmHg, RT, 16 h) .

Yield = 2.09 g (91 %) [α]o = - 4.2°

-~® (R)-2-(4-Benzyloxyphenoxy)-l-ethoxypropane (2D)

This compound was prepared using a similar method to that described for compound 2C. Quantities used: compound 105 (2.50 g, 9.69 mmol), 1-bromoethane (1.22 g, 11.20 mmol), ^~ -5 sodium hydride (0.89 g, 30 % dispersion, 12 mmol) and dry N,N-dimethylformamide (40 ml) . The residue was purified by flash chromatography [fine mesh silica gel; 4 % (v/v) ethyl acetate in petrol (bp 40-60 °C) ] to give a pale oil which was dried in vacuo (P ₂ 0 ₅ , 0.15 mmHg, RT, 16 h) .

20

Yield = 2.59 g (94 %) [α]o = + 1.7°

25

30

(R)-2-(4-Benzyloxyphenoxy)-1-propoxypropane (2E)

This compound was prepared using a similar method to that described for compound 2C. Quantities used: compound 105 (2.50 g, 9.69 mmol), 1-bromopropane (1.33 g, 10.82 mmol), sodium hydride (0.86 g, 30 % dispersion, 11 mmol) and dry N,N-dimethylformamide (60 ml) . The residue was purified by flash chromatography [fine mesh silica gel; 4 % (v/v) ethyl acetate in petrol (bp 40-60 °C) ] to give a colorless oil which was dried in vacuo (CaCl ₂ , 0.10 mmHg, RT, 5 h) .

Yield = 1.86 g (64 %) [αp = + 1.2°

(R)-2-(4-Benzyloxyphenoxy)-l-butoxypropane (2F)

This compound was prepared using a similar method to that described for compound 2C. Quantities used: compound 105 (2.54 g, 9.85 mmol), 1-bromopropane (1.48 g, 10.80 mmol), sodium hydride (0.89 g, 30 % dispersion, 12 mmol) and dry N,N-dimethylformamide (60 ml) . The residue was purified by flash chromatography [fine mesh silica gel; 4,5 % (v/v) ethyl acetate in petrol (bp 40-60 °C) ] to give a pale oil which was dried in vacuo (CaCl ₂ , 0.10 mmHg, RT, 7 h) .

Yield = 1.87 g (60 %)

(R)-2-(4-Benzyloxyphenoxy)-1-pentoxypropane (2G)

This compound was prepared using a procedure similar to that described for compound 2C. Quantities used: compound 105 (2.51 g, 9.73 mmol), 1-bromopentane (1.60 g, 10.60 mmol), sodium hydride (0.85 g, 30 % dispersion, 11 mmol) and dry N,N-dimethylformamide (60 ml) . The residue was purified by flash chromatography [fine mesh silica gel; 4 % (v/v) ethyl acetate in petrol (bp 40-60 °C) ] to give a colorless oil which was dried in vacuo (CaCl ₂ , 0.12 mmHg, RT, 5 h) .

Yield = 1.97 g (62 %)

(R)-2-(4-Benzyloxyphenoxy)-l-hexoxypropane (2H)

This compound was prepared using a similar method to that described for compound 2C. Quantities used: compound 105 (2.50 g, 9.69 mmol), 1-bromohexane (1.70 g, 10.30 mmol), sodium hydride (0.85 g, 30 % dispersion, 12 mmol) and dry N,N-dimethylformamide (60 ml) . The residue was purified by flash chromatography [fine mesh silica gel; 4 % (v/v) ethyl acetate in petrol (bp 40-60 °C) ] to furnish a colorless oil which was dried in vacuo (P ₂ 0 _5/ 0.12 mmHg, RT, 5 h) .

Yield = 2.47 g (75 %) [αp = + 4.5°

(R)-2-(4-Benzyloxyphenoxy)-1-dodecyloxypropane (21)

This compound was prepared using a similar method to that described for compound 2C. Quantities used: compound 105 (0.79 g, 3.06 mmol), 1-bromododecane (0.88 g, 3.53 mmol), sodium hydride (0.26 g, 30 % dispersion, 4 mmol) and dry N,N-dimethylformamide (40 ml) . The residue was purified by flash chromatography [fine mesh silica gel; 5 % (v/v) ethyl acetate in petrol (bp 40-60 °C) ] to give a colorless syrup which was dried in vacuo (P ₂ 0 ₅ , 0.30 mmHg, RT, 5 h) .

Yield = 0.85 g (65 %) [αp = + 3.4°

(R)-2-(4-Hydroxyphenoxy)-l-methoxypropane (2J)

10 % Palladium-on-charcoal (0.10 g) was suspended in a stirred solution of compound 2C (2.03 g, 7.46 mmol) in ethyl acetate (50 ml) at room temperature. The reaction mixture was thoroughly degassed under reduced pressure and then stirred under hydrogen at atmospheric pressure for 18 h; TLC analysis then showed the absence of starting material. The catalyst was removed by filtration through a pad of "Hyflo supercel", and the filtrate was then evaporated under reduced pressure to give a pale yellow oil. The crude product was purified by flash chromatography [fine mesh silica gel; 9:1 dichloro- methane-petrol (bp 40-60 °C) ] to give a yellow syrup which was dried in vacud (P ₂ 0 ₅ , 0.20 mmHg, RT, 72 h) .

Yield = 1.12 g (82 %) [αp = - 9.6°

(R)-2-(4-Hydroxyphenoxy)-1-ethoxypropane (2K)

This compound was prepared using a similar method to that described for compound 2J. Quantities used: compound 107 (2.49 g, 8.71 mmol), 10 % palladium-on-charcoal (0.10 g) and ethyl acetate (50 ml) . The residue was purified by flash chromatography [fine mesh silica gel; 9:1 dichloromethane- petrol (bp 40-60 °C) ] to give a colorless syrup which was dried in vacuo (P ₂ 0 ₅ , 0.30 mmHg, RT, 5 h) .

Yield = 0.94 g (55 %) [αp = - 5.3°

(R)-2-(4-Hydroxyphenoxy)-1-propoxypropane (2L)

This compound was prepared using a similar method to that described for compound 2J. Quantities used: compound 108 (1.81 g, 6.03 mmol), 10 % palladium-on-charcoal (0.09 g) and ethyl acetate (50 ml) . The residue was purified by flash chromatography [fine mesh silica gel; dichloromethane] to give a yellow syrup which was dried in vacuo (P ₂ 0 ₅ , 0.13 mmHg, RT, 5 h) .

Yield = 0.99 g (78 %) [αp •= + 1.6°

(R)-2-(4-Hydroxyρhenoxy)-1-butoxypropane (2M)

This compound was prepared using a similar method to that described for compound 2J. Quantities used: compound 109 (1.85 g, 5.89 mmol), 10 % palladium-on-charcoal (0.09 g) and ethyl acetate (50 ml) . The residue was purified by flash chromatography [fine mesh silica gel; dichloromethane] to give a yellow syrup which was dried in vacuo (P ₂ O ₅ , 0.12 mmHg,

RT, 16 h) .

Yield = 1.05 g (79 %) [αp = + 2.7°

(R)-2-(4-Hydroxyphenoxy)-1-hexoxypropane (20)

This compound was prepared using a similar method to that described for compound 2J. Quantities used: compound 111 (2.39 g, 6.99 mmol), 10 % palladium-on-charcoal (0.10 g) and ethyl acetate (50 ml) . The residue was purified by flash chromatography [fine mesh silica gel; 9:1 dichloromethane- petrol (bp 40-60 °C) ] to afford a pale yellow syrup which was dried in vacuo (P 0 ₅ , 0.15 mmHg, RT, 6 h) .

Yield = 1.28 g (73 %) [αp = + 1.4°

(R)-2-(4-Hydroxyphenoxy)-1-dodecloxypropane (2P)

This compound was prepared using a similar method to that described for compound 2J. Quantities used: compound 112 (0.80 g, 1.88 mmol), 10 % palladium-on-charcoal (0.07 g) and ethyl acetate (50 ml) . The residue was purified by flash chromatography [fine mesh silica gel; dichloromethane] to give an orange syrup which was dried in vacuo (P ₂ 0 ₅ ,

0.30 mmHg, RT, 15 h) .

Yield = 0.53 g (84 %)

Example 3

(R)-2-[4-(4 '-Pentylbiphenyl-4-carbonyloxy)phenoxy]-1-methoxy- propane (3A)

Dicyclohexylcarbodiimide (0.33 g, 1.50 mmol) was added to a stirred mixture of compound 4 ^" -Pentylbiphenyl-4-carboxylic acid (0.35 g, 1.31 mmol), compound 2J (0.38 g, 1.33 mmol), 4-N,N-dimethylaminopyridine (0.05 g, 0.41 mmol) and dry dichloromethane (20 ml) . The reaction was stirred at room temperature for 18 h; TLC analysis showed the reaction to be complete. The precipated urea derivative was removed by filtration and the filtrate was washed with water (20 ml) ,

5 % (v/v) acetic acid (2 x 50 ml) , water (20 ml) ; the organic phase was then dried (MgS0 ₄ ) , filtered and evaporated under

reduced pressure to give a colorless solid. The crude product was purified by flash chromatography [fine mesh silica gel; 4 % (v/v) ethyl acetate in petrol (bp 40-60 °C) ] , recrystal- lized (cyclohexane x 2) and dried in vacuo (P ₂ O ₅ , 0.12 mmHg,

45 °C, 8 h) .

Yield = 0.16 g (28 %) K 73.3 B 93.3 S _A 131.6 Ch 135.2 (°C)

[αp = - 2.5°

The following chiral compounds are obtained analogously:

OAlkyl Compound No. Alkyl Chain Transition Temperatures (°C) fain

3B Ethyl K _X 51.1 K ₂ 75.5 B 92.4 S _A 126.2 I -7.9

3C Propyl K _λ 65.0 K ₂ 72.9 B 87.6 S _A 127.7 I +3.6

3D Butyl K _x 31.2 K ₂ 62.0 B 80.0 S _A 108.9 I +0.6

3E Pentyl K ₂ 41.6 K ₂ 57.6 B 79.4 S _A 105.3 I +4.3 3F Hexyl K _x 51.6 K ₂ 59.8 B 80.1 S _A 104.6 I +5.4

H,C Λ OAlkyl

Com ound No. Alk l Chain Transition Temperatures (°C) JO

K-t 69.3 K ₂ 83.5 B 85.5 S _A 107.5 Ch 122.7 1+1.3 Kj _. 43.3 K ₂ 59.7 B 80.1 S _A 105.1 Ch 112.4 I +1.1 K 54.8 B 73.9 S _A 95.8 Ch 100.8 I +3.5

K 48.8 B 73.6 S _A 89.5 Ch 93.7 BP 94.0 I +9.7 K 46.3 B 68.1 S _A 83.2 Ch 86.7 BP 86.7 I +2.6 K 44.5 B 62.8 S _A 74.0 Ch 78.4 BP 78.4 I +5.6 K 59.9 (S _A 43.6 Ch 44.7 BP 52.7) 1 +2.8

(R/S) OAlkyl

Compound No. Alky Chain Transition Temperatures (°C)

3N Methyl K 52.6 B 77.1 S _A 104.5 N 121.6 I

30 Ehyl K 41.2 B 79.8 S _A 102.7 N 111.2 I

Transition Temperatures (°C) Ifilfi K 34.3 S _A 41.4 Ch 85.6 I +4.2 K 17.5 S _A 45.6 Ch 74.5 I +2.7 K 18.2 S _A 25.1 Ch 54.7 I +5.0 K 1.4 S _A 9.5 Ch 32.8 I +3.2 K 2.6 S _A 13.6 Ch 35.8 I +4.1 K 0.6 S _A 15.8 Ch 42.1 I +4.1

Transition Temperatures (°C) K 54.3 (S _A 24.5) Ch 81.2 I +10.3 K 40.6 (S _A 4.9) Ch 50.1 I + 4.2 K 36.2 (S _A 6.0) Ch 47.4 I + 4.5 K < -20 (S _A -4.1) Ch 18.6 I + 5.7 K < -20 (S _A -10.0) Ch 7.7 I + 4.4 K < -20 Ch -6.1 I + 8.1

The assessment of optical purity was performed by incremental addition of (+)-europium tris(D-3-heptafluorocamphorate) (16) to the -H NMR sample until resolution occured.

Suitable downfield shifts were observed for the protons at positions 2 and 6 (ten atoms away from the chiral centre) ; the protons appear as doublets which resonate at approxi¬ mately δ 8.10 ppm in the absence of the chiral shift reagent.

The doublet for the racemic compound was resolved into iden¬ tical doublets on addition of sufficient chiral shift reagent, demonstrating the validity of the method (as shown overleaf) .

In an identical experiment performed on the chiral compound, no resolution was achieved for the aromatic proton signal, only a large downfield shift. This implies that the chiral 1-alkoxypropane system is essentially pure, within experimen¬ tal error which was estimated to be - 1 %.

The same -tH-NMR shift experiment was carried out with a chiral propanone ester for formula

It was revealed, that this material had ee values ranging from 69-75 %. This reflects the inherent instabiliy of these materials towards racemization.

Example 4

A mixture is made of

49.3 % of Compound No. 3R

50.7 % of Compound No. 3T which exhibits a greeny-blue reflectance at room temperature and

K < -50 S _A 18.9 Ch 49.9 I

Example 5

A mixture is formulated containing the following components

Compound No. 3Zb 49.1 % Compound No. 3Y 50.9 %

and shows a deep blue reflectance at room temperature with the following transitions: K < -40 S _A 7.8 Ch 38.8 I.