Ferroelectric liquid crystal compositions containing chiral haloalkoxy tail units

Abstract

The subject application discloses a chiral nonracemic composition of the general formula:

R₁ --Ar--O--CH₂ --C*HX--C*HY--CH₂ --O--R₂

wherein R₁ is an achiral tail of two to sixteen carbons; Ar is an achiral flc core of at least two rings; * denotes a chiral carbon; X and Y are halogens; and R₂ is one to ten carbon atoms. The --O--CH₂ --C*HX--C*HY--CH₂ --O-- segment comprises the chiral proximal segment of the chiral tail; the proximal segment is selected from the enantiomers 2R,3R-dihalo and 2S,3S-dihalo. R₂ is the distal segment of the chiral tail.

Description

This invention was made with partial support of the United States Government under National Science Foundation Grant no. ISI8722712. The United States Government has certain rights in this invention.

Relatedness of the Application

This application is a continuation-in-part of U.S. Ser. No.164,233, filed Mar.4, 1988, now U.S. Pat. No. 5,051,506 which is incorporated herein in its entirety by reference.

FIELD OF THE INVENTION

The present invention relates to ferroelectric liquid crystals useful in electro-optical and display device applications.

BACKGROUND OF THE INVENTION

Liquid crystals have found use in a variety of electrooptical and display device applications, in particular those which require compact, energy-efficient, voltage-controlled light valves such as watch and calculator displays. These devices are based upon the dielectric alignment effects in nematic, cholesteric and smectic phases of the liquid crystal compound in which, by virtue of dielectric anisotropy, the average molecular long axis of the compound takes up a preferred orientation in an applied electric field. Since the coupling to an applied electric field by this mechanism is rather weak, the resultant electro-optical response time may be too slow for many potential applications.

Liquid crystal displays have a number of unique characteristics, including low voltage and low power of operation, which makes them perhaps the most promising of the non-emissive electro-optical display candidates available with today's technology. However, slow response and insufficient nonlinearity can impose limitations for many potential applications. The requirement for speed may become especially important in proportion to the number of elements which have to be addressed in a device. This may result in increasingly impractical production costs for the potential use of such devices in flat-panel displays for use in video terminals, oscilloscopes, radar and television screens.

It has been shown by N. A. Clark and S. T. Lagerwall in Appl. Phys. Lett. 36:899 (1980) and in U.S. Pat. No. 4,367,924 that electro-optic effects with sub-microsecond switching speeds are achievable using the technology of ferroelectric liquid crystals (FLCs). Some display structures prepared using FLC materials, in addition to the high speed (about 1,000 times faster than currently used twisted nematic devices) reported by these investigators, also exhibit bistable, threshold sensitive switching, making them potential candidates for light modulation devices including matrix addressed light valves containing a large number of elements for passive displays of graphic and pictorial information, as well as for optical processing applications. A recent review of the applications of FLC devices is given by Lagerwall, S.T. and Clarke, N.A. (1989) Ferroelectrics 94:3-62.

Smectic C liquid crystal phases composed of chiral, nonracemic molecules possess a spontaneous ferroelectric polarization, or macroscopic dipole moment, deriving from a dissymmetry in the orientation of molecular dipoles in the liquid crystal phases (Myer et al. (1975) J. Phys. (Les Ulis, Fr) 36:L-69). The ferroelectric polarization density is an intrinsic property of the material making up the phase and has a magnitude and sign for a given material under a given set of conditions. In ferroelectric liquid crystal display devices, like those of Clark and Lagerwall, appropriate application of an external electric field results in alignment of the molecules in the ferroelectric liquid crystal phase with the applied field. When the sign of the applied field is reversed, realignment or switching of the FLC molecules occurs. This switching can be employed for light modulation. Within a large range of electric field strengths, the switching speed (optical rise time) is inversely proportional to applied field strength and polarization or dipole density (P), and directly proportional to orientational viscosity. Fast switching speeds are then associated with FLC phases which possess high polarization density and low orientational viscosity.

A basic requirement for application of ferroelectric liquid crystals in such devices is the availability of chemically stable liquid crystal compounds or mixtures which exhibit ferroelectric phases (chiral smectic C) over a substantial temperature range about room temperature. In some cases, the ferroelectric liquid crystal compound itself will possess an enantiotropic or monotropic ferroelectric (chiral smectic C*) liquid crystal phase. Ferroelectric liquid crystal mixtures possessing smectic C* phases with useful temperature ranges can also be obtained by admixture of chiral, nonracemic compounds, designated ferroelectric liquid crystal dopants into liquid crystal host material (which may or may not be composed of chiral molecules). Addition of the dopant can affect the ferroelectric polarization density and/or the viscosity of the C* phase and thereby affect the switching speed. Desirable FLC dopants are molecules which impart high ferroelectric polarization density to an FLC material without significantly increasing the orientational viscosity of the mixture. The components of FLC mixtures can also be adjusted to vary phase transition temperatures or to introduce desired LC phases.

Thermotropic liquid crystal molecules typically possess structures which combine a rigid core coupled with two relatively "floppy" tails (see Demus et al. (1974) Flussige Kristalle In Tabellen, VEB Deutscher Verlag fur Grundstoffindustrie, Lebzig for a compilation of the molecular structures of LC molecules). FLC materials have been prepared by the introduction of a stereocenter into one of the tails, thus introducing chirality. The first FLC compound to be characterized was DOBAMBC (Meyer et al., supra) which contains a 2-methylbutyl chiral tail. Pure DOBAMBC exhibits a smectic C* phase with a ferroelectric polarization of -3 nC/cm².

There are a number of reports of compounds containing phenylbenzoate, diphenyl, phenylpyrimidine and related cores coupled to chiral tail units which possess monotropic smectic C* phases displaying fast switching speeds at room temperature, or which can be employed as FLC dopants to induce high polarization and fast switching speeds when combined in mixtures with FLC host materials.

The following are exemplary reports of such FLC compounds:

Walba et al., U.S. Pat. No. 4,556,727 reports phenylbenzoates having non-racemic 2-alkoxy-1-propoxy tails. Eidman and Walba, U.S. Pat. No. 4,777,280 report chiral 1-cyanoalkoxy phenylbenzoates. Walba and Razavi, U.S. Pat. No. 4,695,650 report chirally asymmetric reverse ester phenylbenzoates having chiral 1-haloalkyl tail units.

Ohno et al. (1989) U.S. Pat. No. 4,795,587 refers to liquid crystal compounds exhibiting smectic C phases which contain a phenylpyridine core having the formula: ##STR1## where R¹ is an alkyl group having seven to twelve carbon atoms and R² is an alkyl group having five to twelve carbon atoms.

Japanese patent documents JP 63264573 and JP 62258361 refer to optically active 6-substd.-pyridine-3-carboxylic acid esters useful as ferroelectric smectic liquid crystals. Optically active 6-substituted-pyridine-3-carboxylic acid esters obtained from reaction of dodecyloxybenzoic acid, thionyl chloride and 6-hydroxynicotinic acid (S)-2-methylbutyl ester are specifically referred to. Japanese patent document JP 62175465 refers to ester compounds contained in liquid crystal compositions exhibiting nematic phases. 2-(trans-4-ethyl-cyclohexyl)-5-nicotinic acid-3-fluoro-4-cyanophenyl ester is referred to specifically.

Walba et al. (1986) J. Amer. Chem. Soc. 108:7424-7425 and Walba and Vohra, U.S. Pat. No. 4,648,073 and U.S. Pat. No. 4,705,874 disclose ferroelectric (chiral) smectic liquid crystal compounds having an achiral core and chiral tail units derived from (2,3)-alkyloxiranemethanols which possess a high ferroelectric polarization density. The ferroelectric liquid crystal materials reported have the following general formulas: ##STR2## where R is an alkyl of one to seven carbon atoms and R' is an alkyl of five to twelve carbon atoms and Ar is phenylbenzoate or biphenyl.

Hemmerling et al. (1988) European Patent Application, Pub. No. 263437 refers to chiral aryl-2,3-epoxyalkylethers FLC compounds having phenylpyrimidine or phenylpyridazine cores of the formula: ##STR3## where A is a diazine-2,5,-diyl or diazine-3,6-diyl, R¹ is a straight chain or branched alkyl group having 1-12 carbon atoms wherein one or two non-neighboring CH₂ groups is replaced with an O or S atom, R²-4 are, independent of one another, H, a straight chain alkyl group having 1-12 carbon atoms or a branched alkyl group having 3-10 carbon atoms wherein R¹, R² and R³ are not all H. Compounds in which R² and R³ are both H having extrapolated polarization densities (P_ext) in the range from 30-70 nC/cm₂ are reported.

Walba and Razavi, U.S. patent application Ser. No. 099,074, now allowed, discloses chirally asymmetric phenyl and biphenylbenzoates having chiral 2,3-epoxy alkyl or 1-halo-2,3-epoxy alkyl tails which are useful as components of FLC materials. The compounds disclosed have the formula: ##STR4## where R' is an alkyl or alkoxyl group having three to fifteen carbon atoms, R is an alkyl group having three to fifteen carbon atoms, n=1 or 2, and Y is a halogen or hydrogen. It is also disclosed, therein, that 1-haloepoxides of formula A can impart higher polarization densities and higher switching speeds in FLC mixtures than their diastereomers of formula B. It is suggested that the difference in properties of A and B is due to the relative alignment of the epoxide and halogen bond dipoles in the isomer. ##STR5##

Furukawa, K. et al. (1988) Ferroelectrics 85:451-459 refers to chiral smectic C compounds having an ester group in the core and an optically active tail group, either alkoxy or alkoxy carbonyl, with an electronegative substituent, either a halogen or cyano group, ortho to the chiral tail, for example: ##STR6## where X=H, Halogen or CN.

Wand et al., U.S. Ser. No. 360,397 discloses methyl epoxides having the formula ##STR7## where Ar₂ is a phenylbenzoate, biphenyl phenylpyrimidine or phenyl pyridine, R is an alkyl or alkoxy group, and R' is an alkyl group containing 3 to 12 carbon atoms.

While a number of useful ferroelectric liquid crystal materials (both pure compounds and mixtures) have been reported, there is a growing need for FLC materials with varying properties of temperature range, tilt angle and switching speed for use in varied applications. Further, there is a need for FLC dopants with varying mixing properties (which are dependent, at least in part, on chemical composition) for use in the preparation of FLC mixtures. FLC dopants which impart high polarization density to, and retain low viscosity in, such mixtures are of particular interest.

SUMMARY OF THE INVENTION

The present invention provides a class of chirally asymmetric molecules which are useful as components of ferroelectric liquid crystal materials. These compounds can impart the properties of high ferroelectric polarization density and fast electro-optical switching speeds on low polarization materials when mixed with such materials to form ferroelectric liquid crystal compositions. Alternatively, certain of the compounds of the present invention in pure form can also possess stable smectic C* phases having high polarization density.

The composition of the subject invention comprises a chiral nonracemic composition of the general formula:

R₁ --Ar--O--CH₂ --C*HX--C*HY--CH₂ --O--R₂

wherein:

R₁ is an achiral tail of two to sixteen carbons; Ar is an achiral FLC core of at least two rings; * denotes a chiral carbon; X and Y are halogens; and R₂ is one to ten carbon atoms. The --O--CH₂ --C* HX--C* HY--CH₂ --O-- segment comprises the chiral proximal segment of the chiral tail; the proximal segment is selected from the enantiomers 2R,3R-dihalo and 2S,3S-dihalo. R₂ is the distal segment of the chiral tail.

The compositions comprising 2R,3R-dihalo and 2S,3S-dihalo proximal segment enantiomers are represented by the following general formulas where Q=R₂ : ##STR8## The compositions of the subject invention can be derived from R₁ --Ar--O--CH₂ --C* HX--C* --HY--CH₂ --OH intermediates, i.e., compounds of formulas IXa and IXb where Q=H. In the final ferroelectric compositions of the subject invention, Q=R₂.

X and Y can be the same or different halides. For example, the chiral proximal segment, epoxies, the polarization density of the FLC mixture increases linearly. Depending on the intended application and desired polarization of the FLC mixture, a person of skill in the art can determine the appropriate concentration of subject compositions to incorporate in a host material to obtain the desired polarization. Because the polarization densities of the subject applications are high, low concentrations are typically used as dopants to obtain the desired polarization in the mixture. Generally, the concentrations of the dopants used in the host are less than about 20% (w/w). Such low concentrations avoid orientational viscosity that may be associated with the use of higher concentrations of such dopants.

Compositions of the subject invention can be mixed with any suitable host material. Suitable host materials vary with the intended application, but generally, solubility or miscibility with the dopant, broad C* phase temperature range (e.g., -20°C to 60 °C) and low orientational viscosity are considered desirable.

An important aspect of the present invention is the finding that some of the compounds having proximal segments of formulas IXa and IXb (Q=R₂), can have improved polarization properties as FLC dopants relative to those of analogous compounds having only one oxygen in the chiral tail:

______________________________________
Analogous Compound    Tilt   Pext
______________________________________
4'-(2S,3S-difluorohexyloxy)phenyl-
25°
300 nC/cm2
5-hexylpyrimidine
2-[4'-(2S,3S-difluorohexyloxy)-
phenyl]-5-hexylpyrimidine
4'-(2S,3S-difluorohexyloxy)phenyl-
25°
280 nC/cm2
5-heptylpyrimidine
2-[4'-(2S,3S-difluorohexyloxy)-
phenyl]-5-heptylpyrimidine
______________________________________

As can be seen from Table 2, the esters, XI, XIII, XIV, and XVI, show improved extrapolated polarization relative 2-[4'-(2S,3S-S-difluorohexyloxy-phenyl difluorohexyloxy)phenyl]-5-hexylpyrimidine. The esters, XII and XV, also show improved extrapolated polarization relative to 2-[4'-(2S,3S-difluorohexyloxy)phenyl]-5-hept ylpyrimidine.

For comparison with the subject compositions of Table 2, the P_ext for these analogous compounds is the extrapolated polarization from a 10% by weight mixture of the compounds in W82.

The improved polarization of the subject compositions is believed to be due to the relative alignment of the dipoles of the halide(s) and oxygens of the chiral tail. It should be noted that it is dipole orientation of the subject conformations in the oriented smectic C phase that affects polarization density. Only the components of the dipoles normal to the tilt plane affect polarization. The structure of the proximal and distal segments of the achiral tail and any steric and/or electronic interaction between the groups will affect dipole orientation and the magnitude and sign of the polarization density. The relationship between dipole alignment and ferroelectric polarization density has been discussed for related molecules in Walba et al. (1986) J. Amer. Chem. Soc. 108:5210-5221 and Walba et al. (1986) J. Amer. Chem. Soc. 108:7424-7425, both of which are incorporated herein by reference.

As exemplified herein, the incorporation of the proximal chiral segment of the subject invention,--O--CH₂ --C* HX--C* HY--CH₂ --O--, and any of a variety of distal segments described herein, into an FLC compound can produce an FLC dopant that demonstrates improved polarization properties.

EXAMPLES

PAC Example

Synthesis of 2-[4'-(2R,3R-dihalo-4-hydroxy)butyloxy]phenyl hydroxybutyloxy)phenyl]-5-R₁ -pyrimidines

This example illustrates the synthesis of chiral 2-[4'-(2,3-dihalo-4-hydroxy)butyloxy]phenyl hydroxybutyloxy)phenyl]-5-R₁ -pyrimidines. The procedure is illustrated by the synthesis of the difluoride, 2-[4'-(2R,3R-difluoro-4-hydroxy)butyloxy]phenyl-5-hexylpyridine hydroxybutyloxy)phenyl]-5-hexylpyrimidine (IXa, where R₁ =hexyl, Q=H, Ar=2-phenylpyrimidine, and X and Y=F).

Initially, L-diethyl tartrate (Ia) (I50 g or 728 mmol), dimethoxypropane (179 ml or 1.45 mol), and toluenesulfonic acid (TsOH) (2.78 g or 14.6 mmol) were added to a 500 ml flame-dried flask containing a magnetic stir bar. The reaction was allowed to stir 12 hours, and then an additional 90 ml (0.73 mol) dimethoxypropane was added. The reaction was allowed to stir an additional 24 hours, at which time approximately 160 ml of the solution was removed by fractional distillation, after which an additional 90 ml (0.73 mol) dimethoxypropane was added. Approximately one hour later, the reaction mixture was poured into a 10% aqueous NaHCO3 solution and extracted with a 1:1 (v/v) hexane:ethyl acetate solvent mixture. The combined organic layers were then extracted with saturated NaCl, dried over a mixture of anhydrous Na₂ SO₄ and K₂ CO₃, and the solvent was removed in vacuo to produce a dark oil. The oil was then fractionally distilled at 110°- 120°C, giving a yield of 128 g of a 1:1 (by gas chromatograph) mixture of the desired acetonide (II) and an unidentified side product.

To a three liter oven-dried 3-neck flask equipped with a mechanical stirring rod, an addition funnel, and a condenser, was added 29.6 g (0.78 mol) lithium aluminum hydride (LAH) and 1.5 1 dry ether. To the addition funnel was then added to the acetonide (II) mixture and approximately 300 ml ether. The LAH suspension was stirred at a rapid rate and cooled in an ice bath to 0°C The acetonide solution was then allowed to slowly drip into the suspension over the course of approximately 40 minutes, after which the ice bath was removed and the reaction was allowed to stir a further 90 minutes. The ice bath was then replaced and the reaction mixture was treated by dropwise addition of 29.2 ml of water, 29.6 ml of a 1.5 g/1 aqueous NaOH solution, and 89 ml water. The suspension was allowed to stir overnight. To the suspension was added 20 g anhydrous MgSO₄, and after a further 15 minutes stirring, the reaction mixture was filtered through a 1 inch pad of celite, which was washed with ether, and the solvent was removed in vacuo. The resulting yellow oil was distilled at 112°C at 3 mm Hg to give 38.6 g (33% yield over two steps) of the product, 2S,3S-isopropylidenethreitol (III), as a clear oil.

Next, 2S,3S-isopropylidenethreitol (III) (20 g or 123 mmol), benzyl chloride (14.19 ml or 123 mmole), dichloromethane (78 ml), NaOH solution (90.6 ml of 4M), and tetrabutylammonium bromide (1.99 g or 6.2 mmol) were added to a 500 ml flask containing a magnetic stir bar. A reflux condensor was attached to the top of the flask, and the biphasic reaction was allowed to reflux with stirring for about 30 hours. The reaction mixture was then poured into a separatory funnel and the layers were separated. The aqueous layer was extracted twice more with dichloromethane. The combined organic layers were dried over a mixture of anhydrous Na₂ SO₄ and K₂ CO₃, and the solvent was removed in vacuo. The oil was then fractionally distilled, with the product, 4-benzyloxy-2S,3S-isopropylidenethreitol (IV), coming over at 138° C. (3mm Hg) to give a yield of 20.9 g (67% yield).

Next, 2S,3S-acetonide-4-benzyloxythreitol (IV) (6.543 g or 25.9 mmol) and toluenesulfonyl chloride (9.888 g or 51.9 mmol) were added to a 250 ml flame-dried flask containing a magnetic stir bar. The flask was cooled in an ice bath, and 78 ml of ice-cold anhydrous pyridine was added. The reaction mixture was stirred in the ice bath for one hour, then allowed to sit in a -20°C cooler overnight. The reaction mixture was poured into water and extracted three times with diethyl ether. The combined organic layers were then extracted with a saturated NaCl solution, dried over anhydrous sodium sulfate, and the solvents removed in vacuo to give 10.25 g (98% yield) of 4-benzyloxy-2S,3S-isopropylidene-1-(4-toluenesulfonate)threitol (V) as a viscous oil.

To produce 2-{ ([4'-(4-benzyloxy-2S,3S-O-isopropylidenedioxy)-butyloxy]}phenyl isopropylidenedioxybutyloxy)phenyl]- 5-hexylpyrimidine; 4-benzyloxy-2S,3S-isopropylidene-1-(4-toluenesulfonate)threitol (V) (2.00 g or 5.0 mmol), 4-hexylpyrimidylphenol (R₁ --ArOH, where R₁ =hexyl) (1.525 g or 6.0 mmol) and dimethylformamide (15 ml) were added to a 25 ml flame-dried flask containing a magnetic stir bar. The mixture was stirred while 274 mg (5.7 mmol) of a 1:1 (w/w) NaH/mineral oil mixture was slowly added. The reaction was allowed to stir overnight at which time it was heated to 73°C to force the reaction to completion. The reaction mixture was then poured into 25 ml of water, and extracted with a 1:1 (v/v) hexane:ethyl acetate solvent mixture. The combined organic layers were then extracted with saturated NaCl, dried over a mixture of anhydrous sodium sulfate and potassium carbonate, and the solvent was removed in vacuo. The product was purified by flash chromoatography using a 35 mm silica gel column and a 4:1 hexane:ethyl acetate solvent to afford 2.36 g (97% yield) of the desired product, 2-{ [4'-(4-benzyloxy-2S,3S-O-isopropylidenedioxy)butyloxy]}phenyl isopropylidenedioxybutyloxy)phenyl]-5-hexylpyrimidine (VI, where R₁ =hexyl), as a waxy solid.

To obtain 2-[4'-(4-benzyloxy -2S,3S -dihydroxy)butyloxy]phenyl benzyloxy-2S,3S-dihydroxybutyloxy)phenyl]-5-hexylpyrimidine ; 2{ [4'-(4-benzyloxy-2S,3S-0-isopropylidenedioxy)butyloxy]}phenyl O-isopropylidenedioxybutyloxy)phenyl]-5-hexylpyrimidine (2.08 g or 4.2 mmol), tetrahydrofuran (16 ml), water (12 ml), and concentrated HCl (3.5 ml) were added to a 50 ml flask containing a magnetic stir bar. The reaction was allowed to stir (approximately 8 hours) until no further starting material remained as evidenced by TLC. The reaction mixture was then poured into water and extracted with ether. The combined organic layers were then extracted with saturated NaCl, dried over a mixture of anhydrous Na₂ SO₄ and K₂ CO₃, and the solvent was removed in vacuo. The reaction was purified by flash chromatography on silica gel using 1:1 (v/v) hexane:ethyl acetate as an eluent, affording 191 g (100% yield) of the 2-[4'-(4-benzyloxy-2S,3S-dihydroxy)butyloxy]phenyl dihydroxybutyloxy)phenyl]-5-hexylpyrimidine (VII, where R₁ =hexyl), as a waxy solid.

To make 2-[4'-(4-benzyloxy-2S,3S-difluoro)butyloxy]phenyl-hexylp yrimidine difluorobutyloxy)phenyl]-5-hexylpyrimidine; 1.52 g (3.37 mmol) of 2-[4'-(4-benzyloxy-S,3S-dihydroxybutyloxy)]phenyl 2S,3S-dihydroxybutyloxy)phenyl]-5-hexylpyrimidine and 40 ml of dichloromethane were added to a flame-dried 50 ml flask containing a magnetic stir bar. The solution was cooled to -78°C with stirring, and 2.7 ml (20 mmol) of DAST were slowly added. The reaction was allowed to warm to -30°C over the course of an hour, at which time 2.3 ml (28 mmol) of anhydrous pyridine were added. The reaction was slowly warmed to room temperature and allowed to stir overnight. The reaction mixture was then slowly added to a 10% aqueous NaHCO₃ solution, from which it was extracted with methlylene chloride. The combined organic layers were then dried over a mixture of anhydrous Na₂ SO₄ and K₂ CO₃, and the solvent was removed in vacuo. The product was then purified by flash chromoatography on a silica column using 4:1 (v/v) hexane:ethyl acetate as the eluent, affording 838 mg (55% yield) of 2-[4'-(4-benzyloxy-2S,3S-difluoro)butyloxy]phenyl difluorobutyloxy)phenyl]-5-hexylpyrimidine (VIII, where R₁ =hexyl and X and Y=F), as a viscous oil.

To make 2-[4'-(2R,3R-difluoro-4-hydroxy)butyloxy]phenyl hydroxybutyloxy)phenyl]-5-hexylpyrimidine; 838 mg (1.84 mmol) of 2-[4'-(4-benzyloxy-2S,3S-difluorobutyloxy)]phenyl difluorobutyloxy)phenyl]-5-hexylpyrimidine and 10 ml of methylene chloride were added to a 50 ml flame-dried flask containing a magnetic stir bar. The stirred solution was cooled to 0°C and 2.03 ml of a 1 M BBr₃ solution was slowly added over 5 minutes while stirring. The reaction was stirred a further 15 minutes, at which time the reaction mixture was slowly added to a 10% (w/v) NaHCO₃ solution, from which it was extracted with methylene chloride. The combined organic layers were then dried over a mixture of anhydrous Na₂ SO₄ and K₂ CO₃, and the solvent was removed in vacuo. The product was then purified by flash chromatography on a silica column using 3:2 (v/v) hexane:ethyl acetate as the eluent, affording 540 mg (80% yield) of 2-[4'-(2R,3R-difluoro--hydroxy)butyloxy]phenyl hydroxybutyloxy)phenyl]-5-hexylpyrimidine (IXa, where R₁ =hexyl, X and Y=F and Q=H).

Example 1a

PAC Synthesis of Compounds containing the chiral 2R,3R-dihalo-4-hydroxybutyloxy segment coupled to other R₁ -substituted Cores

In the synthesis of compound VI from compound V in Scheme 1, any 4-R₁ -4'-hydroxy substituted para-substituted phenylpyridines FLC core (R₁ --ArOH) can be used. For example, the synthesis of 4'-phenol-5-alkylpyridine is described in Ohno et al., U.S. Pat. No. 4,795,587 (1989) (see compound V therein). 4'-phenol-5-alkylpyridine can then be used in the method of Example 1 to synthesize many different chiral 4- alkylphenyl-4'-(2R,3R-dihalo-4-hydroxybutyloxy)pyrimidine para-substituted phenylpyridine compounds, having a variety of achiral tails.

Other R₁ -ArOH compounds such as 4-R₁ -4'-hydroxybiphenyl, 4-R₁ -phenyl-4'-hydroxybenzoate, 4-hydroxyphenyl-4'R₁ -benzoate, and other R₁ -substituted core units using cores described hereinabove are commercially available or can be synthesized by methods known in the art from readily available starting materials.

Other R₁ -ArOH compounds can be used in the synthesis of all IXa and IXb (Q=H) enantiomers and regioisomers of the subject invention.

Example 2

PAC Synthesis of 2-(4' [4'-( 2S,3S-dihalo-4-hydroxybutyloxy) phenyl hydroxybutyloxy)phenyl]-5-R R₁ -pyrimidines

This example illustrates the synthesis of chiral 2-[4'-(2S,3S-dihalo-4-hydroxy)butyloxy]phenyl-5-alkylpyrimidines(IXb hydroxybutyloxy)phenyl]-5-alkylpyrimidines (IXb, where Q=H, Ar=2-phenylpyrimidine, and X and Y=halides). This method can be used to obtain the enantiomers of compounds produced by the methods of any of the Examples described herein. The method for obtaining 2-(4' [4'-2S,3S-dihalo-4-hydroxybutyloxy)phenyl hydroxybutyloxy)phenyl]-5-R₁ -pyrimidines is substantially the same as the method described in Example 1 with the exception that compound Ia, L-diethyl tartrate, is replaced with its enantiomer, Ib, D-diethyl tartrate D-diethyl tartrate, like L-diethyl tartrate, is commercially available.

The enantiomer of the compound produced by Example 1, when the D-diethyl tartrate is used in place of L-diethyl tartrate, is 2-[4'-(2S,3S-difluoro-4-hydroxy)butyloxy]phenyl hydroxybutyloxy)phenyl]-5-hexylpyrimidine.

Example 3

PAC Synthesis 2-[4'-(2R,3R-difluoro-4-formyl-butyloxy)phenyl-4 formyloxybutyloxy)phenyl]-5-n-hexylpyrimidine (X)

To make compound X, 30 mg (82 μmol) of 2-[4'-(2R,3R-difluoro-4-hydroxybuyloxy)]phenyl hydroxybutyloxy)phenyl]-5-hexylpyrimidine (IXa, where R=hexyl, Q=H and X and Y=F) and 10 ml of methyl formate were added to a 10 ml flame-dried flask containing a magnetic stir bar. Approximately 10 μl titatnium isopropoxide was then added to the solution as a transesterification catalyst, and the reaction was stirred 12 hours. At this time a further 10 μl catalyst was added, and the milky white reaction was stirred for five minutes, at which time it was poured into water and extracted with ether. The combined organic phases were washed with a saturated NaCl solution, dried over a mixture of anhydrous Na₂ SO₄ and K2CSO₃, and the solvent was removed in vacuo. The product was purified by flash chromatography on a silica column using 3:2 (v/v) hexanes:ethyl acetate as the eluent, affording 28.0 mg (87% yield) of 2-[4'-(2R,3 R-difluoro-4-formyl-butyloxy)phenyl-4 formyloxybutyloxy)phenyl]-5-n-hexylpyrimidine (X).

Example 4

PAC Syntheses of 2-[4'-(2R,3R-difluoro-4-alkylester-butyloxy)phenyl-4 alkylesterbutyloxy)phenyl]-5-alkylpyrimidines (XI-XV) and 2-[4'-(2R,3R-difluoro-4-alkenylester-butyloxy)phenyl-4.] . alkenylesterbutyloxy)phenyl]-5-alkylpyrimidines (XVI) Example 4a

Synthesis of 2-[4'-(2R,3R-difluoro-4-acetyl-butyloxy)phenyl-4 acetoxybutyloxy)phenyl]-5-n-hexylpyrimidine (XI)

To make compound XI, 55 mg (.151 mmol) of 2-[4'-(2R,3R-difluoro-4-hydroxy)butyloxy]phenyl hydroxybutyloxy)phenyl]-5-hexylpyrimidine (IXa, where R₁ =hexyl, Q=H and X and Y=F), 33 μl (0.45 mmol) of acetic anhydride, 110 μl (1.4 mmol) of pyridine, 1.5 ml of THF, and about 2 mg of DMAP were added to a 10 ml flame-dried flask containing a magnetic stir bar. The reaction was allowed to stir overnight. It was then poured into water and extracted with ether. The combined organic phases were washed once each with a dilute NaOH and a saturated NaCl solution, dried over a mixture of anhydrous Na₂ SO₄ and K2CSO₃, and the solvent was removed in vacuo. The product was purified by flash chromatography on a silica column using 4:1 (v/v) hexanes:ethyl acetate as the eluent, affording 46.2 mg (75%) yield of the product, 2-[4'-(2R,3R-difluoro-4-acetyl-butyloxy)phenyl-4 acetyloxybutyloxy)phenyl]-5-n-hexylpyrimidine (XI).

Example 4b

PAC Synthesis of 2-[4'-(2R,3R-difluoro-4-acetylbutyloxy)phenyl-4 acetyloxybutyloxy)phenyl]-5-n-heptylpyrimidine (XII)

To make compound XII, the same procedure for making compound XI was followed with the exception that 2-[4'-(2R,3R-difluoro-4-hydroxy)butyloxy]phenyl hydroxybutyloxy)phenyl]-5-heptylpyrimidine (IXa, where R₁ =heptyl, Q=H and X and Y=F) was used in place of 2-[4'-(2R,3R-difluoro-4-hydroxy)butyloxy]phenyl hydroxybutyloxy)phenyl]-5-hexylpyrimidine.

Example 4 4c

PAC Synthesis of 4'-[(2R,3R-difluoro-4-propanoate)butyloxy]phenyl-4-hexylpyrimidine 2-[4'-(2R,3R-difluoro-4-propanoatebutyloxy)phenyl]-5-hexylpyrimidine (XIII)

To make compound XIII, the procedure for making compound XI was followed with the exception that propanoyl chloride was used in place of acetic anhydride.

Example 4d

PAC Synthesis of 4'-[(2R,3R-difluoro-4-butanoate)butyloxy]phenyl-4-hexylpyrimidine 2-[4'-(2R,3R-difluoro-4-butanoatebutyloxy)phenyl]-5-hexylpyrimidine (XIV)

To make compound XIV, the procedure for making compound XI was followed with the exception that butanoyl chloride was used in place of acetic anhydride.

Example 4c

PAC Synthesis of 4'-[2R,3R-difluoro-4-pentanoate)butyloxy]phenyl-4-heptylpyrimidine 2-[4'-(2R,3R-difluoro -4-pentanoatebutyloxy)phenyl]-5-heptylpyrimidine (XV)

To make compound XV, the procedure for making compound XII was followed with the exception that pentanoyl chloride was used in place of acetic anhydride.

Example 4f

PAC Synthesis of 4'-{[2R,3R-difluoro-4-(4-pentenoate)]-butyloxy}phenyl-4-hexylpyrimidine 2-{4'-[2R,3R-difluoro-4-(pent-4-enoate)butyloxy]phenyl}-5-hexylpyrim idine (XVI)

To make compound XVI, the procedure for making compound XI was followed with the exception that 4-pentenoyl chloride was used in place of acetic anhydride.

Example 5

PAC Syntheses of 4'-[(2R,3R-dihalo-4-alkoxy)butyloxy]phenyl-4-alkylpyrimidines 2-[4'-(2R,3R-dihalo-4-alkoxybutyloxy)phenyl]-5-alkylpyrimidines and 4'-[2R,3R-dihalo-4-(epoxyalkoxy)butyloxy]phenyl-4-alkylpyrimidines 2-[4'-(2R,3R-dihalo-4-epoxyalkoxybutyloxy)phenyl]-5-alkylpyrimidines (XVII, XVIII, XIX, XX, XXI, XXIII)

Example 5a

PAC Synthesis of 4'-[(2R,3R-difluoro-4-methoxy)butyloxy]phenyl-4-heptylpyrimidine 2-[4'-(2R,3R-difluoro-4-methoxybutyloxy)phenyl]-5-heptylpyrimidine (XVII)

To make compound XVII, 18.6 mg (49 μmol) of 2-[4'-(2R,3R-difluoro-4-hydroxy)butyloxy]phenyl-5-heptylpyrimidine 2-[4'-(2R,3R-difluoro-4-hydroxybutyloxy)phenyl]-5-heptylpyrimidine and 4 ml of THF were added to a 10 ml flame-dried flask containing a 2 magnetic stir bar. To this solution was added 5 mg (98 μmol) of a 1:1 (w/w) NaH/mineral oil mixture, 12 μl (200 μmol) of methyl iodide, and 1 ml DMF. The reaction was allowed to stir overnight. The reaction was then poured into water and extracted with 1:1 (v/v) hexane:ethyl acetate. The combined organic layers were then extracted with saturated NaCl, dried over a mixture of anhydrous Na₂ SO₄ and K₂ CO₃, and the solvent was removed in vacuo The reaction mixture was purified by a flash chromatography on silica column using 4:1 (v/v) hexane:ethyl acetate as an eluent, affording 16.3 mg (84%) of 4'-[(2R,3R-difluoro-4-methoxy)butyloxy]phenyl-4-heptylpyrimidine 2-[4'-(2R,3R-difluoro-4-methoxybutyloxy)phenyl]-5-heptylpyrimidine (XVII).

Example 5b

PAC Synthesis of 4'-[(2R,3R-difluoro-4-butyloxy)butyloxy]phenyl-4-heptylpyrimidine 2-[4'-(2R,3R-difluoro-4-butyloxybutyloxy)phenyl]-5-heptylpyrimidine (XVIII)

To make compound XVIII, the method for making compound XVII was followed with the exception that 1-butyl iodide was used in place of methyl iodide.

Example 5c

PAC Synthesis of 4'-[2R,3R-difluoro-4-(4-pentenoxy)butyloxy]phenyl-4-hexylpyrimidine 2-{4'[2R,3R-difluoro-4-(pent-4-eneoxy)butyloxy]-phenyl}-5-hexylpyrim idine (XIX)

To make compound XIX, the method for making compound XVII was followed with the exceptions that: (1) 2-[4'-(2R,3R-difluoro-4-hydroxy)butyloxy]phenyl-5-hexylpyrimidine 2-[4'-(2R,3R-difluoro-4-hydroxybutyloxy)phenyl]-5-hexylpyrimidine was used instead of 2-[4'-(2R,3R-difluoro-4-hydroxy)butyloxy]phenyl-5-heptylpyrimidine, 2-[4'-(2R,3R-difluoro-4-hydroxybutyloxy)phenyl]-5-heptylpyrimidine and (2) 4-pentenyl iodide was used instead of methyl iodide.

Example 5d

PAC Synthesis of 4'-[2R,3R-difluoro-4-(1-methylheptyloxy)butyloxy]phenyl-4-hexylpyrimidi ne 2-{4'-[2R,3R-difluoro-4-(R-1-methylheptyloxy)butyloxy]phenyl}-5-hexy lpyrimidine (XX)

To synthesize compound XX, the method for making compound XVII was followed with the exceptions that: (1) XVII was followed 2-[4'-(2R,3R-difluoro-4-hydroxy)butyloxy]phenyl-5-hexylpyrimidine 2-[4'-(2R,3R-difluoro-4-hydroxybutyloxy)phenyl]-5-hexylpyrimidine was used instead of 2-[4'-(2R,3R-difluoro-4-hydroxy)butyloxy]phenyl-5-heptylpyrimidine 2-[4'(2R,3R-difluoro-4-hydroxybutyloxy)phenyl]-5-heptylpyrimidine.Ia ddend., and (2) 1-methylheptyl iodide was used instead of methyl iodide.

Example 5e

PAC Synthesis of 4'-{[2R,3R-difluoro-4-(2R,3R-epoxy)hexyloxy]butyloxy}phenyl-4-hexylpyri midine 2-{4'-[2R,3R-difluoro-4-(2R,3R-epoxyhexyloxy)butyloxy]phenyl}-5-hexy lpyrimidine (XXI)

To synthesize the compound XXI, the method for making compound XVII was followed with the exceptions that: (1) 2-[4'-(2R,3R-difluoro-4-hydroxy)butyloxy]phenyl-5-hexylpyrimidine 2-[4'-(2R,3R-difluoro-4-hydroxybutyloxy)phenyl]-5-hexylpyrimidine was used instead of 2-[4'-(2R,3R-difluoro-4-hydroxy)butyloxy]phenyl-5-heptylpyrimidine 2-[4'-(2R,3R-difluoro-4-hydroxybutyloxy)phenyl]-5-heptylpyrimidine.I addend., and (2) 2R,3R-epoxyhexyl tosylate was used in place of methyl iodide.

Example 5f

PAC Synthesis of 4'-{[2R,3R-difluoro-4-(2S,3S-epoxy)hexyloxy]butyloxy}phenyl-4-hexylpyri midine 2-{4'-[2R,3R-difluoro-4-(2S,3S-epoxyhexyloxy)butyloxy]phenyl}-5-hexy lpyrimidine (XXIII)

To synthesize compound XXIII, the method for making compound XVII was followed with the exceptions that: (1) 2-[4'-(2R,3R-difluoro-4-hydroxy)butyloxy]phenyl-5-hexylpyrimidine 2-[4'-(2R,3R-difluoro-4-hydroxybutyloxy)phenyl]-5-hexylpyrimidine was used instead of 2-[4'-(2R,3R-difluoro-4-hydroxy)butyloxy]phenyl-5-heptylpyrimidine 2-[4'-(2R,3R-difluoro-4-hydroxybutyloxy)phenyl]-5-heptylpyrimidine.I addend., and (2) 2S,3S-epoxyhexyl tosylate was used in place of methyl iodide.

Example 6

PAC Synthesis of chiral 4'-[2,3-dihalo-4-(2,3-dihaloalkoxy)butyloxy]phenyl-4-alkylpyrimidines.] 2-{4'-[2,3-dihalo-4-(2,3-dihaloalkoxy)butyloxy]phenyl}-5-alkylpyrimi dine

Example 6a

PAC Synthesis of 4'-[ 2R,3R-difluoro-4-(2S,3S-difluorohexyloxy)butyloxy]phenyl-4-hexylpyrimidine 2-{4'-[2R,3R-difluoro-4-(2S,3S-difluorohexyloxy)butyloxy]phenyl}-5-h exylpyrimidine (XXIV)

To synthesize compound XXIV, 57.1 mg (0.123 mmol) of compound XXIII and 1.0 ml of dichloromethane were added to a 20 ml polyethylene bottle containing a magnetic stir bar. The solution was cooled to 0° C, 35 μl (1.2 mmol) of a commercial mixture of hydrogen fluoride in pyridine was then added, and the reaction was allowed to stir for approximately three hours, at which time the reaction was judged complete by TLC analysis. The reaction mixture was then poured into dilute Na₂ CO₃ solution, from which it was extracted with dichloromethane. The combined organic layers were then dried over a mixture of anhydrous Na₂ SO₄ and K₂ CO₃, and the solvent was removed in vacuo to give the fluorohydrin.

The fluorohydrin was then dissolved in 1.2 ml of dry dichloromethane and transferred into a flame-dried 10 ml flask containing a magnetic stir bar. The solution was cooled to -78°C and 49 μl (0.37 mmol) diethylaminosulfurtrifluoride (DAST) was added. The reaction was allowed to warm to -30°C over the course of an hour, at which time 40 μl (0.49 mmol) anhyrous pyridine was added. The reaction was allowed to warm at room temperature and was stirred overnight. The reaction mixture was then slowly poured into a dilute NaHCO₃ solution, from which it was extracted with dichloromethane. The combined organic layers were dried over a mixture of anhydrous Na₂ SO₄ and K₂ CO₃, and the solvent was removed in vacuo. The reaction mixture was purified by flash chromatography on a silica gel column successively using 9:1 (v/v) hexane:ethyl acetate as eluents, affording 19.7 mg (33%) of the tetrafluoro compound, XXIV, ¹9 NMR of this compound shows three multiplets, two of equal size at -199.5 and -203.8, the other twice that size at -205.5; ¹ H NMR shows a five multiplet group centered at 5.0 δ and a four multiplet group centered at 4.6 δ.

Example 6b

PAC Synthesis of 4'-[2R,3R-difluoro-4-(2R,3R-difluorohexyloxy)butyloxy]phenyl-4-hexylpyr imidine 2-{4'-[2R,3R-difluoro-4-(2R,3R-difluorohexyloxy)butyloxy]phenyl}-5-h exylpyrimidine (XXII)

To synthesize compound XXII, the method for making compound XXIV was followed with the exception that compound XXI was used in place of compound XXIII.

This invention has been described and illustrated by reference to several preferred embodiments, but it is not intended to limit the invention by doing so. It is intended that the invention encompass all enantiomers and regioisomers of the general formula:

R₁ --Ar--O--CH₂ C*HX--C*HY--CH₂ --O--R₂

where the proximal segment is a 2R,3R-dihalo or a 2S,3S-dihalo. It is also intended that the invention include mixtures of two or more compositions of the subject invention, and FLC formulations in which these compounds are admixed with each other or with other compounds including LC and FLC materials.

Claims

1. A chiral nonracemic compound of the formula:

R₁ --AR--O--CH₂ --C*HX--C*HY--CH₂ --O--R₂

wherein

* denotes a chiral carbon,

X and Y are halogens selected from the group of chlorine and fluorine, the --O--CH₂ --C*HX--C--HY--CH₂ --O-- --O--CH₂ --C*HX--C*HY--CH₂ --O-- segment comprises the chiral proximal segment of the chiral tails, said proximal segment being selected from the enantiomers 2R,3R-dihalo and 2S,3S-dihalo,

R₁ is an achiral alkyl, alkyl sulfide, alkyl ether, alkenyl, alkenyl sulfide, alkenyl ether, alkoxy, alkoxy sulfide, or alkoxy ether group of two to sixteen carbons,

Ar is an achiral flc core selected from the group consisting of phenylbenzoates, phenylpyrimidines, biphenyls, phenylpyridines, biphenylbenzoates, diphenylpyrimidines, diphenylpyridines, terphenyls, phenyldiazenes, diphenyldiazenes, and diphenylthiadiazoles, and the chiral proximal segment and R₁ para-substituted with respect to each other on outer rings of said core, and R₂ is a distal segment of the chiral tail comprising one to ten carbon atoms and is selected from the group consisting of alkdehyde, alkyl acyl, alkyl, alkenyl, alkenyl acyl, alkyl halide, alkenyl halide, alkyl epoxide, and alkenyl epoxide.

2. The compound of claim 1, wherein R₁ comprises five to sixteen carbons.

3. The compounds of claim 4, wherein R₁ comprises eight carbons.

4. The compound of claim 1, wherein R₁ is selected from the group of straight-chain or branched.

5. The compound of claim 1, wherein R₂ comprises three carbons.

6. The compound of claim 1, wherein R₂ is selected from the group of straight-chain and branched.

7. The compound of claim 1, wherein R₂ comprises a chiral carbon.

8. The compound of claim 1, wherein R₂ is an alkyl halide consisting of two halogens.

9. The compound of claim 1, wherein said alkyl halides comprise fluorine or chlorine.

10. The compound of claim 1, wherein said composition is selected from the group consisting of 4'-[(2R,3R-difluoro-4-formyl)-butyloxy]phenyl-4-hexylpyrimidine 2-4'-(2R,3R-difluoro-4-formyloxybutyloxy)phenyl]-5-hexylpyrimidine (X); 4'-[(2R,3R-difluoro-4-acetyl)butyloxy]phenyl-4-hexylpyrimidine 2-[4'-(2R,3R-difluoro-4-acetoxybutyloxy)phenyl]-5-hexylpyrimidine (XI); 4'-[(2R,3R-difluoro-4-acetyl)butyloxy]phenyl-4-heptylpyrimidine 2-[4'-(2R,3R-difluoro-4-acetoxybutyloxy)phenyl]-5-heptylpyrimidine (XII); 4'-[(2R,3R-difluoro-4-propanoate)butyloxy]phenyl-4-hexylpyrimidine 2-[4'-(2R,3R-difluoro-4-propanoatebutyloxy)phenyl]-5-hexylpyrimidine (XIII); 4'-[(2R,3R-difluoro-4-butanoate)-butyloxy]phenyl-4-hexylpyrimidine 2-[4'-(2R,3R-difluoro-4-butanoatebutyloxy)phenyl]-5-hexylpyrimidine (XIV); 4'-[(2R,3R-difluoro-4-pentanoate)butyloxy]phenyl-4-heptylpyrimidine 2-[4'-(2R,3R-difluoro-4-pentanoatebutyloxy)phenyl]-5-heptylpyrimidin e (XV); 4'-[2R,3R-difluoro-4-(4-pentanoate)-butyloxy]phenyl-4-hexylpyrimidine.] . 2-{4'-[2R,3R-difluoro-4-(pent-4-enoate)butyloxy]phenyl}-5-hexylpyrim idine (XVI); 4'-[2R,3R-difluoro-4-methoxy)butyloxy]-phenyl-4-heptylpyrimidine 2-[4'-(2R,3R-difluoro-4-methoxybutyloxy)phenyl]-5-heptylpyrimidine (XVII); 4'-[(2R,3R-difluoro-4-butyloxy) butanoxy]phenyl-4-heptylpyrimidine 2-4'( 2R,3R-difluoro-4-butyloxybutyloxy)phenyl]-5-heptylpyrimidine (XVIII); 4'-(2R,3R-difluoro-4-(4-pentenoxy)-butyloxy)phenyl-4-hexylpyrimidine 2-{4'-[2R,3R-difluoro-4-(pent-4-enoxy)butyloxy]phenyl}-5-hexylpyrimi dine (XIX); 4'-(2R,3R-difluoro-4-(1-methylheptyloxy)buty oxy)- phenyl-4-4-hexylpyrimidine 2-{4'-[2R,3R-difluoro-4-(R-1-methylheptyloxy)butyloxy]phenyl}-5-hexy lpyrimidine (XX); 4'-{[2R,3R-difluoro-4-(2R,3R-epoxy)hexyloxy]butyloxy}phenyl-4-hexylpy.] . 2-{4'-[2R,3R-difluoro-4-(2R,3R-epoxyhexyloxy)butyloxy]phenyl}-5-hexy lpyrimidine (XXI); 4'-{[2R,3R-difluoro-4-(2S,3S-epoxy)hexyloxy]butyloxy}phenyl-4-hexylpyri midine 2-{4'-[2R,3R-difluoro-4-(2S,3S-epoxyhexyloxy)butyloxy]phenyl}-5-hexy lpyrimidine (XXIII); 4'-[2R,3R-difluoro-4-(2S,3S-difluorohexyloxy)butyloxy]phenyl-4-hexylpyr imidine 2-{4'-[2R,3R-difluoro-4-(2S,3S-difluorohexyloxy)butyloxy]phenyl}-5-h exylpyrimidine (XXIV); and 4'-[2R,3R-difluoro-4-(2R,3R-difluorohexyloxy)butyloxy]phenyl-4-hexylpyr imidine 2-{4'-[2R,3R-difluoro-4-(2R,3R-difluorohexyloxy)butyloxy]phenyl}-5-h exylpyrimidine (XXII).

11. An flc composition comprising the compound of claim 1.