GB2058789A

GB2058789A - Fluorophenols

Info

Publication number: GB2058789A
Application number: GB8031248A
Authority: GB
Original assignee: BDH Chemicals Ltd; UK Secretary of State for Defence
Current assignee: BDH Chemicals Ltd; UK Secretary of State for Defence
Priority date: 1979-10-02
Filing date: 1980-09-26
Publication date: 1981-04-15
Also published as: GB2058789B

Abstract

An intermediate useful in the production of liquid crystal esters has a molecular structure <IMAGE> in which of the groups R' and R'' one is fluorine and the other is hydrogen, and in which R is an alkyl group having more than one carbon atom, an aryl substituted alkyl group or a cyclohexyl substituted alkyl group. These compounds may be prepared from the corresponding alkoxy compounds <IMAGE> where R''' is a protective alkyl group such as methyl. These compounds may be used in the production of liquid crystal esters by a conventional esterification with carboxylic acids, or acid derivative, e.g. chloride, e.g. containing the radical <IMAGE> where X is an alkyl group and <IMAGE> is a benzene or cyclohexane ring.

Description

SPECIFICATION Intermediates useful in the production of liquid crystal compounds The present invention relates to intermediates useful in the production of liquid crystal compounds.

The use of liquid crystal materials to exhibit electro-optic effects in display devices such as digital calculators or watches is now well-known. One of the parameters of a liquid crystal material which is important in relation to electro-optical operation is the dielectric anisotropy (aye) of the material. This is the difference, for a given frequency and temperature, between the average dielectric constant measured parallel (E g ) to the long axis of the molecules of the material, eg when aligned together, less the average dielectric constant measured perpendicular ( ) to the long axis of the molecules.

The sign and magnitude of the dielectric anisotropy of a given liquid crystal material is one of the major parameters which determine the kinds of electro-optic devices in which that material may be used.

For example, materials having a large positive dielectric anisotropy, herein referred to as 'strongly positive' materials may be used in known twisted nematic effect devices. For example mixtures of 4alkyl-or-alkoxy-4'-cyanobiphenyls and a 4"-alkyl-or-alkoxy-cyano-p-terphenyl have achieved considerable commercial success in such applications.

Materials having a large negative dielectric anisotropy may for example (depending on other properties such as resistivity) be used in known dynamic scattering effect and cholesteric memory effect devices.

Materials having a small positive or negative dielectric anisotropy, herein referred to as 'weakly' positive or negative materials as appropriate, may be mixed with either strongly positive materials or strongly negative materials to modify the dielectric anisotropy.

For example weakly positive or negative materials are useful for blending with strongly positive materials for multi-plexed twisted nematic effect devices. Furthermore, they may alsc be blended with strongly negative materials to form suitable mixtures for positive contrast guest-host devices.

It is the purpose of the present invention (in one aspect) to facilitate the synthesis of liquid crystal compounds which are either weakly positive or weakly negative materials (preferably negative).

The sign and magnitude of the dielectric anisotropy of a liquid crystal material is determined (inter alia) by the resultant dipole moment of the molecules of the material which in turn is determined by the various substituents within the molecule. Positive materials have a resultant dipole moment along the long axis of the molecule, whilst negative materials possess a resultant dipole moment at right angles to the long axis of the molecule.

The known group of liquid crystals based on the ester structure (I) as given below in which the six membered ring A may be aromatic or saturated and in which both rings carry appropriate substituents in the 4 and 4' positions,

may show positive or negative dielectric anisotropy according to the degree of interactions of the 4 and 4' substituents with the dipole produced by the central carbonyl grouping. Incorporation of a powerfully electronegative grouping in the 4' position, such as a cyano-grouping, for example, induces a resultant dipole along the axis of the molecule and hence confers positive dielectric anisotropy.On the other hand, if the 4 and 4' substituents are but weakly electron attracting or releasing, the direction of the resultant dipole moment is determined by the carbonyl group, and the component of its dipole at right angles to the long axis of the molecule may confer negative dielectric anisotropy.

Ester structures may be substituted in such a way that additional dipoles are introduced into the molecule to reinforce the component of the carbonyl dipole at right angles to the molecular axis, with the object of at least slightly enhancing the negative dielectric anisotropy or diminishing the positive dielectric anisotropy of the molecule.

It is apparent superficially that such an objective may be achieved by introducing polar groups into the 2', 3', 5' and 6' positions of ring B. However it is well-known that the introduction of groupings in these positions may, because of their steric influence, diminish the lateral attractions between the molecules which produce liquid crystal properties. Such substituted molecules may not show liquid crystal properties at all, or may show only monotropic phases.

The discovery has now been made, which is further described in our co-pending UK Patent Application, that in general terms the substitution of fluorine atoms in the 2' or 3' positions of ester structure (I) slightly enhances the negative dielectric anisotropy or diminishes the positive dielectric anisotropy of the molecule by the mechanism described above, but, more importantly, still retains liquid crystal properties in the molecules. The present invention provides the intermediate phenols and methods of manufacturing them which enable such fluoro-substituted esters to be prepared.

According to the present invention in a first aspect, an intermediate useful in the production of liquid crystal esters has a molecular structure:

in which R' represents a hydrogen or fluorine atom, R" represents fluorine when R' = H or hydrogen when R' = F, and R represents an alkyl grouping with more than 1 carbon atom which may be a straight chain alkyl grouping, or a branched alkyl group, which may contain an optically active carbon atom, or where R may represent an aralkyl or cyclohexyl substituted alkyl grouping.

According to the present invention in a second aspect there is provided the use of an intermediate of structure (II) in the production of a liquid crystal ester, including reacting the intermediate with the carboxylic acid of a cycloalkyl or aryl compound.

For example a method of producing a liquid crystal ester having a structure

involves an esterification of a phenol having structure (II) above together with an acid or acid derivative containing the group

where

is a benzene or cyclohexane ring and X is an alkyl group where

is a benzene or cyclohexane ring or X is an alkoxy, alkanoyloxy or alkoxy carbonyloxy group where

is a benzene ring, R, R' and R" being as defined above. (When A is a cyclohexane ring the stereochemistry is such that the 1,4 substituents are trans).

The esters of structure (III) are further described in copending U.K. Patent Application No 7934127, although examples of the use according to the second aspect are given below.

5 ORill ,W, OR"' Route 1 4 Route 2 '1F R * R H2-CH CH3 IH,-CH L 3 OH t OH $-. R CH2-CH3

where R is as defined above and R"' is a protective alkyl group such as methyl.

Typically, but not restrictively, 3-fluoro-4-substituted-phenols embodying structure (II) above may be synthesised by Route 3 as follows: Route 3

where R is as defined above. R"' is a protective alkyl grouping such as methyl.

Examples of the preparation and properties of phenols having structure (II) as defined above will now be given.

EXAMPLE 1 A 3-necked flask was fitted with stirrer, thermometer, dropping funnel and calcium chloride drying tube, and immersed in an ice-salt bath. Anhydrous aluminium chloride (1 06g) and dichloromethane (250ml) were placed in the flask and stirred vigorously whilst a solution of valeryl chloride (95.5g) 2fluoroanisole (1009) in dichloromethane (250ml) was added at a rate sufficiently slow to ensure that the temperature of the reaction did not rise above 1 50 (approx 1 hour). When the addition was complete, the reaction was stirred overnight, the temperature being allowed to rise to room temperature.

The reaction was poured onto ice (1.5kg) with vigorous stirring, and stirred for 30 minutes. The organic layer was separated off, and the aqueous layer extracted with dichloromethane (1 50ml). The combined organic layers were washed with water (150 ml) dried (Na2SO4), filtered and the solvent removed by distillation, finally under slight vacuum. The crude 4-valeryl-2-fluoroanisole a slightly yellow low-melting solid, was used directly without further purification.

A small quantity was distilled, b.pt. 100--1020C at 0.15 mm. NMRT9.0 (m,CH3-CH2), 8.5 (m,CH2-CH2), 7.2 (t,CH2-CO), (s, OCH3), 2,2-3,3 (m, aromatic H).

tic 1 spot (CH2Cl2) glc 99.7% pure 4-Valeryl-2-fluoroanisole (from 1009 2-fluoroanisole), hydrazine hydrate (102ml), potassium hydroxide (52.59) and 1 :2-dihydroxyethane (1.01) were placed in a flask equipped with stirrer, double surface condenser and thermometer, and boiled under reflux for 1 T hours at 1 500 C. The apparatus was arranged for distillation, and liquid was distilled until the temperature in the flask reached 1 900 C. The distillate was retained. The apparatus was arranged for reflux, which was continued for 12 hours, after which the reaction was allowed to cool.

The distillate was extracted with petroleum spirit (b.p 4060O, 2 x 1 50ml). The cooled reaction was poured into cold water (2 litres) and extracted with petrol (1 x 500ml, 2 x 150ml). The five petrol extracts were combined, washed with water (250ml) and the petrol removed by distillation. The light yellow oily residue (60g) was distilled under high vacuum through a small Vigreux column (6", B24), and a small forerun was discarded. 4-Pentyl-2-fluoroanisole, a colourless oil, had b.pt 72-750C at 0.2 mm.

Yield 499 (31% theory) tic 1 spot (1:1 dichloromethane: petrol) 4-Pentyl-2-fiuoroanisole (499), 479/0 hydrobromic acid (196ml) and 45% hydrogen bromide in acetic acid (294ml) were boiled together under reflux for 18 hours. The hydrogen bromide that was evolved was absorbed in water with a scrubber.

The reaction was cooled to 150C, poured into water (1.01) and extracted with dichloromethane (3 x 250ml). The combined extracts were washed with water (2 x 500ml), dried (Na2SO4, 30 min), filtered and the solvent removed by distillation. The dark oily residue (469) was distilled under high vacuum through a 6" Vigreux column. 4-Pentyl-2-fluorophenol, a colourless oil, was collected at b.pt 101-1030C at 0.65 mm, after discarding a small forerun.

Yield 33.29 (73% theory) Analysis: glc 98.5% pure tic 1 spot (CH2Cl2) The 4-alkyl-2-fluorophenols listed in Table 1 were prepared in a similar manner using the appropriate acid chloride at the first stage of the synthesis.

TABLE 1 4-n-Alkyl-2-fluorophenols

Analysis found Analysis required Empirical R Boiling Point formula C H C H C3H7 54-55 C at 0.3mm CgHl,OF 69.7% 7.4% 70.1% 7.2% QH9 68670C at 0.4mm CXoH13OF 71.3% 8.5% 71.4% 7.8% C5H11 68-69 C at 0.3mm C,sHISOF 72.5%. 8.7% 72.5% 8.3% C6Ht3 80-82 C at 0.2mm C,2Hl7oF 73.4% 9.5% 73.4% 8.7% C7H,s 101-103.0C at 0.65mm ClaHtgOF 74.4% 9,5% 74.3% 9.1% C8H,7 125-128 C at 0.9mm C,H2;OF 75.4% 10.2% - 75.0% 9.4% CgH;;g 124 C at 0.6mm C15H2aOF 75.4% 10.3% 75.6% 9.7% C10H21 106 C at 0.5mm C16H25OF 76.0% 10.3% 76.2% 10.0% C > 1H2q 135-136 C at 0.7mm C,7H27OF - - - - Analogous compounds in which R = C2H6, n-C8H,7, n-C,H19 and n-C,OHa, may also be made in a similar way.

EXAMPLE 2 A solution of bromine (48g) in chloroform (100ml) was added during 10 minutes to a well-stirred solution of 2-fluoroanisole (37.8g) in chloroform (100ml). The mixture became warm and hydrogen bromide fumes were evolved. The solution was boiled under reflux with stirring until the colour of the bromine faded (approximately 2 hours). The chloroform was recovered by distillation and the light yellow oily residue was distilled under high vacuum through a small Vigreux column (6 in, B24). 4- Bromo-2-fluoroanisole, a colourless oil, had b.pt 60-61 0C at 0.5 mm. Yield 45.2g (82% theory).

A 500ml flask was equipped with stirrer, dropping funnel and double surface condenser with calcium chloride guard tubes to maintain anhydrous conditions. The flask was placed in an empty water bath and charged with magnesium turnings (3.99) and sodium-dried ether (45ml). A small volume of a solution of 4-bromo-2-fluoroanisole (31.2g) in sodium-dried ether (60ml) was added to the magnesium and a single crystal of iodine, followed by a few drops of 1,2-dibromoethane, was added to initiate the reaction. Once the reaction had begun, the remaining solution of 4-bromo-2-fluoroanisole was added dropwise with stirring so as to maintain the reaction at a steady rate. When the addition was complete, reflux was maintained for a further hour with stirring.The Grignard solution was then cooled in an icebath and cuprous chloride (0.9g) and sodium-dried ether (25ml) were added, followed immediately by a solution of (+)-2-methylbutylbenzene sulphonate (72g) in sodium-dried ether (60ml) at such a rate that the reaction maintained gentie reflux. When the addition was complete the reaction was stirred at room temperature for 24 hours, and then boiled under reflux for a further 16 hours.

The reaction mixture was cooled, and then poured into 10% aqueous hydrochloric acid (225ml) at OOC, and stirred for 1 hour. The ether layer was recovered, and the aqueous layer was extracted with ether (3 x 100ml). The ether layer and extracts were combined, filtered through a small Hyflo pad, washed with water (3 x 100ml), dried (Na2SO4), filtered and the solvent removed by distillation.

The oily residue was distilled on a steambath under high vacuum (0.1 mm) into a cold trap cooled with dry ice, and distillation was continued until condensation of the colourless product ceased. The major part of the product distilled at 60-800C at 0.1 mm. The distillate was redistilled under high vacuum through a small Vigreux column (6 in, B24) and 4-(2-methylbutyl)-2-fluoroanisole was collected at 66-670C at 0.15mm, after discarding a small forerun. Yield 13.49 (45% theory); tic 1 spot (CH2Cl2).

4-(2-Methylbutyl)-2-fluoroanisole (12.4g),47% hydrobromic acid (49.6ml) and 45% hydrogen bromide in acetic acid (74.4ml) were boiled together under reflux for 18 hours. The hydrogen bromide evolved was absorbed in water with a scrubber.

The reaction was cooled to 1 50C, poured into water (250ml) and extraced with dichloromethane (3 x 75ml). The combined extracts were washed with water (2 x 150ml), dried (Na2S04, 30 min), filtered and the solvent removed by distillation. The dark oily residue was distilled under high vacuum through a small Vigreux column (6 in, B24). (+)-4-(2-methylbutyl)-2-fluorophenol, a colourless oil, was collected at b.pt 69-700C at 0.7mm, after discarding a small forerun. Yield 7.0g (61% theory), glc 98.8% pure, tic 1 spot (CH2CI2), [cg] 200/D + 8.0 (c = 4.85 in chloroform).

(+)-4-(2-methylbutyl)-3-fluorophenol may be made in an analogous way.

EXAMPLE 3 3-Fluoroanisole (20g), valeryl chloride (19.19) and aluminium chloride (21.39) were reacted together in dichloromethane (100ml) as described in Example 1 The product, a yellow oil, was distilled under high vacuum through a small Vigreux column (6 in, B24) and four fractions were taken: Fraction 1 b.pt 80-900C at 0.25 mm Fraction 2 b.pt 90-1000C at 0.2 mm Fraction 3 b.pt 100-123 C at 0.1 mm Fraction 4 b.pt 1230C rising at 0.1 mm Fractions 2 and 3, analysed by glc, consisted mainly of the required isomer, whilst Fraction 1 contained a high proportion of 6-valeryl-3-fluoroanisole. Fractions 1 and 4 were combined and chromatographed on a column of silica gel (709).Fractions containing pure 4-valeryl-3-fluoroanisole, eluted with 2:1 petroleum spirit-dichloromethane, were combined. Fractions 2 and 3 were combined and treated similarly (silica gel, 80g). The fractions containing 4-valeryl-3-fluoroanisole were combined and distilled to dryness, finally under vacuum.

The product, a colourless oil, did not crystallise on standing. Yield 149 (42% theory), tic (CH2Cl2) 1 spot, glc 97.7% pure, NMR T 8.9 (t, CH3-CH2), 8.5 (m, CH2-CHk), 7.1 (m, CH2-CO), 6.2 (s, CH3O), 2.0-3.6 (m, aromatic H).

4-Valeryl-3-fluoroanisole (14.19), hydrazine hydrate (8.6ml) potassium hydroxide (4.4g) and 1:2 dihydroxyethane (84ml) were reacted together as described in Example 1. 4-Pentyl-3-fluoroanisole was isolated as a colourless oil b.pt 770C at 0.1 mm. The product showed 1 spot only on tic using dichloromethanepetrol (1:1) as solvent.

4-Pentyl-3-fluoroanisole (2.2g),47% hydrobromic acid (9.0ml) and 45% hydrogen bromide in acetic acid (13.25ml) were reacted together as described in Example 1. The crude product was chromatographed on a column of silica gel (50g) and fractions containing pure 4-pentyl-3-fluorophenol, eluted with 1:1 dichloromethane:petrol were combined and distilled to dryness to leave a light yellow oil. Yield 1.49 (69% theory), glc 96.6% pure, tic 1 spot (CH2Cl2).

The 4-alkylphenols described in Table 2 were prepared by the method above using the appropriate acid chloride.

TABLE 2 4-n-Alkyl-3-fluorophenols Analysis found Analysis required Empirical R formula C H C H n-CsH7 CgH,lOF 69.1% 7.8% 70.1% 7.2% n-C4H9 C,oH,3OF 70.9% 8.5% 71.4% 7.8% n-CsH" Ct,HlsOF 71.7% 8.7% 72.5% 8.3% Analogous. compounds in which R - C2H5 , n-C6H13, n-C7H,s, n-Ct,H,7, n-C,H1g and n-C,oHQ, may also be made in a similar way.

An example of the use of the phenols embodying the invention will now be given. The route is as follows:

where B is a trans-cyclohexane ring, Al being n-alkyl, or where B is a phenyl ring, A1 being n-alkyl or alkoxy.

The preparation of 4-n-pentyl 1-2-fluorophenyl 4'-n-butyloxybenzoate typifies the esterification procedure used to prepare these esters. This compound has been produced as follows.

Step Al 4-n-butyloxybenzoic acid (0.0082M) was converted into the acid chloride using freshly distilled thionyl chloride (15cm3).

Step B1 To a cold, stirred solution of the acid chloride prepared in Step Al in dry dichloromethane (15cm3) was added, dropwise, a cold solution of 4-n-pentyl-2-fluorophenol (0.0082M) in dry dichloromethane (15cm3) and triethylamine (10cm3), keeping the temperature below 1 OOC. When the addition had been completed, the reaction mixture was heated under reflux, with stirring for 3h.

After cooling, the dichloromethane and triethylamine were distilled off, under reduced pressure, and ether was then added to the residue. The undissolved triethylamine hydrochloride was filtered off and the ethereal extract washed successively with 10% hydrochloric acid, 5% aqueous sodium carbonate, and water and finally dried (Na2SO4).

The crude residual ether was then column chromatographed on silica gel, eluting with chloroform (2): light petroleum (bp 6080 ) (1). Several recrystallisations from ethanol gave the 2-fluoro-4-npentylphenyl 4'-n-butyloxybenzoate as a colourless crystalline solid, 1 .9g (61% yield).

Esters such as 2-fluoro-4-b-pentylphenyl 4'-n-butylbenzoate and 2-fluoro-4-n-pentylphenyl trans4'-n-butylcyclohexylcarboxylate were purified by the above chromatographic procedure and then further purified by distillation under reduced pressure, to afford the esters as colourless liquids. The cyclohexane ester mentioned above was further recrystallised from ethanol, using solid carbon dioxide, to give this ester as a colourless crystalline solid, which rapidly melted at room temperature.

Spectroscopic analysis, thin layer chromatography, and gas liquid chromatography were carried out on all the esters prepared by the method to verify their structure and/or purity.

Claims

1. An intermediate useful in the production of liquid crystal esters has a molecular structure

in which of the groups R' and R" one is fluorine and the other is hydrogen and in which R is an alkyl group having more than one carbon atom, an aryl substituted alkyl group or a cyclohexyl substituted alkyl group.

2. An intermediate as claimed in claim 1 and wherein R' is fluorine, Ra is hydrogen and R is alkyl.

3. An intermediate as claimed in claim 1 and wherein R' is hydrogen, R" is fluorine and R is alkyl.

4. An intermediate as claimed in claim 2 and wherein R is n-C3H7.

5. An intermediate as claimed in claim 2 and wherein R is n-C4Hg.

6. An intermediate as claimed in claim 2 and wherein R is n-CsH".

7. An intermediate as claimed in claim 2 and wherein R is n-C6H,3.

8. An intermediate as claimed in claim 2 and wherein R is n-C7H,5.

9. An intermediate as claimed in claim 2 and wherein R is (+)-2-methylbutyl.

1 0. An intermediate as claimed in claim 3 and wherein R is n-C3H7.

11. An intermediate as claimed in claim 3 and wherein R is n-C4Hg.

12. An intermediate as claimed in claim 3 and wherein R is n-C5H".

13. The use of an intermediate as claimed in claim 1 in the production of a liquid crystal ester including the step of reacting the intermediate with the carboxylic acid of a cycloalkyl or aryl compound.

14. The use of an intermediate as claimed in claim 13 and wherein the ester is of the form

where X is an alkyl group and

is a cycloalkyl ring.

1 5. The use of an intermediate as claimed in claim 14 and wherein

is a cyclohexane ring, the stereochemistry being such that the 1,4-substituents are trans. 1 6. The use of an intermediate as claimed in claim 13 and wherein the ester is of the form

where X is an alkyl group, an alkoxy group, an alkanoyloxy group or an alkoxy carbonyloxy group and where

is a benzene ring.