EP0211876A1

EP0211876A1 - Fluorobenzene derivatives

Info

Publication number: EP0211876A1
Application number: EP86901063A
Authority: EP
Inventors: Andreas WÄCHTLER; Hans-Adolf Kurmeier; Reinhard Hittich; Bernhard Scheuble
Original assignee: Merck Patent GmbH
Current assignee: Merck Patent GmbH
Priority date: 1985-02-13
Filing date: 1986-01-30
Publication date: 1987-03-04
Also published as: US4784471A; JPS62501842A; DE3504866A1; WO1986004895A1

Abstract

Dérivés de fluorobenzène de formule (I) où m représente 0,1 ou 2, ainsi que leurs dérivés réactifs, convenant comme produits intermédiaries pour la fabrication de matériaux à cristaux liquides.Fluorobenzene derivatives of formula (I) in which m represents 0.1 or 2, as well as their reactive derivatives, suitable as intermediate products for the manufacture of liquid crystal materials.

Description

Fluorobenzene derivatives

The invention relates to new fluorobenzene derivatives of the formula I.

where m is 0, 1 or 2, and their reactive

Derivatives, which are particularly suitable as intermediates for the production of liquid crystal compounds, and their production.

The use of liquid crystal materials to achieve electro-optical effects in display devices such as digital computers or clocks is generally known today. One of the parameters of liquid-crystalline materials that is important for electro-optical display operation is the dielectric anisotropy (Δε) of the material. For a given frequency and temperature, this is understood to mean the difference between the mean dielectric constant (ε _II ) measured parallel to the longitudinal axis of the molecules of the material, for example with common alignment, and the mean dielectric constant (ε _I ) measured perpendicular to the longitudinal axis of the molecule. Sign and magnitude of the dielectric anisotropy of a given liquid crystal material are one of the most important parameters that determine the type of electro-optical devices in which corresponding materials can be used.

Liquid crystal materials with large positive dielectric anisotropy, hereinafter referred to as "strongly positive" materials, can be used, for example, in known twisted nematic devices. For such applications, for example, mixtures of 4-alkyl-cyanobiphenyls, p-4-alkylcyclohexylbenzonitriles and 4-cyano-4 '- (4-alkylcyclohexyl) biphenyls have been introduced on an economically important scale.

Liquid crystal materials with small positive dielectric anisotropy, hereinafter referred to as "weakly positive" materials, can be mixed with either strongly positive or with strongly negative materials to modify the dielectric anisotropy.

The compounds of formula I, like similar non-laterally fluorinated compounds, e.g. as the compounds listed in DE-OS 29 44 905, are used as intermediates for the synthesis of liquid-crystalline materials with large or small positive dielectric anisotropy.

The invention was based on the object of specifying fluorobenzene derivatives and their preparation which are suitable for the particularly simple synthesis of liquid crystal compounds with weakly positive or strongly positive dielectric anisotropy. It has now been found that the compounds of the formula I are eminently suitable for the one-step synthesis of a large number of target products.

With the provision of the compounds of the formula I, the range of intermediates which are suitable from various points of view for the production of liquid crystals is also very broadly widened.

The invention thus relates to the fluorobenzene derivatives of the formula I.

in which m denotes 0, 1 or 2, their reactive compounds and a process for their preparation, characterized in that a compound of the formula II (m = 1 or 2) is used to prepare cyclohexane carboxaldehydes of the formula I (m = 1 or 2)

reacted with triphenylalkoxymethylphosphonium halide in the presence of a base and the alkoxymethylene compound obtained was treated with an acid, or that for the preparation of benzaldehydes of the formula I (m = 0) a compound of the formula III

in which R ^{1 is} halogen or OH, or their reactive derivatives, oxidized,

or that a compound of formula IV

wherein X ¹ and X ^{2 are} each halogen or X ¹ and X ² together = NOH, hydrolyzed,

or that a compound of formula V,

where X is halogen, a monovalent metal or equivalent, formylates, or that a compound of the formula VI,

in which Q ¹ and Q ² independently of one another denote H, alkyl, unsubstituted or substituted aryl or aralkyl,

treated with ozone and the ozonide obtained reductively cleaves.

The invention furthermore relates to the use of fluorobenzene derivatives of the formula I according to claim 1 as intermediates in the production of liquid crystal materials.

The fluorobenzene derivatives of the formula I and their reactive derivatives can be used according to the invention as intermediates for the production of liquid crystal materials, for example using analogously EP with propane-1,3-diols substituted in the 2-position to give corresponding 1,3-dioxane compounds or with alkyltriphenylphosphonium halides -OS 0 122 389 can be converted into corresponding alkylene compounds. , Suitable reactive derivatives of the compounds of the formula I are primarily acetals of the formula Ia:

in which R ^{2 is} alkyl with 1 to 4 carbon atoms, two radicals R ² together also alkylene with 2 or 3 carbon atoms, and carboxylic acids (or their acid halides) of the formula Ib:

Carboxylic acids of the formula Ib or their reactive derivatives can be converted to 1,3-dioxane derivatives or to alkenyl compounds according to EP-OS 0 122 389 after esterification with suitable phenols or cyclohexanols as described above.

The preparation of the fluorobenzene derivatives according to the invention is exemplified in the following scheme 1. The intermediate ethyl 4-cyan-3-fluorobenzoate from Scheme 1 can also be obtained by oxidation of 2-fluoro-4-methylbenzonitrile and esterification of the benzoic acid obtained or by the following reaction sequence:

Instead of the benzyl halides listed in Scheme 1, the oxidation of which gives the fluorobenzene derivatives according to the invention, the corresponding dihalides (formula IV, X ¹ = halogen, X ² = halogen) can also be used, the hydrolysis of which is known

Methods the compounds of formula I delivers.

The compounds of the formula I can be prepared according to scheme 1 by methods known per se, as described in the literature (e.g. in the standard works such as Houben-Weyl, methods of organic chemistry,

Georg-Thieme-Verlag, Stuttgart) are described, under reaction conditions that are known and suitable for the reactions mentioned. Use can also be made of variants which are known per se and are not mentioned here in detail. All starting materials are known from the literature.

Preferred starting materials are the commercially available chemicals 2-fluoro-4-nitrotoluene, 2-fluoro-4-aminotoluene and p-bromobenzoic acid and 2-fluoro-4-methylbenzonitrile (EP-OS 0 061 907), which are known from the literature and are known from the literature Have methods according to Scheme 1 implemented to form precursors of formulas III, IV, V and VI.

Precursors of the formula III, in which R ^{1 is} preferably halogen, in particular chlorine, bromine or iodine, or OH, can be converted by oxidation into the fluorobenzene derivatives of the formula I according to the invention. Examples of suitable oxidizing agents for the benzyl alcohols of the formula III are chromic acid, CrO ₃ -pyridine complex, bichromate / sulfuric acid, pyridine dichromate, nitric acid, manganese dioxide or selenium dioxide. The is particularly preferred Oxidation with tert-butyl chromate in petroleum ether, benzene or carbon tetrachloride or with manganese dioxide in acetone, petroleum ether, carbon tetrachloride or dilute sulfuric acid.

The benzyl alcohols can also be oxidized indirectly using appropriate reactive derivatives (e.g. tosyl esters) using known methods. The benzyl alcohols can also be converted into the fluorobenzene derivatives according to the invention by treatment with dimethyl sulfoxide, dicyclohexylcarbodiimide or phosphoric acid.

The benzyl halides, in particular the benzyl bromides, of the formula III can be oxidized, for example by methods known from the literature, by treatment with dimethyl sulfoxide, hexamethylene tetramine, 2-nitropropane / NaOEt in EtOH, trimethylamine oxide or potassium dichromate in HMPT in the presence of a crown ether to give the fluorobenzene derivatives according to the invention.

Compounds of the formula IV can be converted into the fluorobenzene derivatives according to the invention by methods known from the literature (oximes, for example by treatment with aqueous acids, NaHSO ₃ or lead tetraacetate).

The compounds of the formula I can furthermore be obtained by formylation of compounds of the formula V in which X is halogen, preferably bromine.

The compounds of formula V are preferably catalytically in the presence of a base at temperatures between room temperature and 220 °, preferably 80 to 150 °, at a pressure of 40 to 160 at, preferably 60 to 100 at, with a CO / H ₂ mixture ( preferably 1: 2 to 2: 1, ins special 1: 1) implemented. The bases used are preferably tertiary amines and the catalyst is preferably dihalobis (triphenylphosphine) palladium (II). Compounds of the formula V in which X is a monovalent metal, preferably lithium, can be converted, for example, by known methods by reaction with N-formylpiperidine into the fluorobenzene derivatives according to the invention. Lithium compounds of the formula V can also be reacted with dihydro-1,3-oxazines by known methods. The addition products obtained can be hydrolyzed to fluorobenzene derivatives of the formula I.

Compounds of the formula V, in which X is MgHalogen, can be converted into fluorobenzene derivatives of the formula I by known methods by reaction with N-alkyl derivatives of 2-oxazolines in the presence of HMPT.

Another variant for the preparation of the fluorobenzene derivatives according to the invention is the reaction of compounds of the formula VI with ozone and subsequent reductive cleavage of the ozonides obtained. Q ¹ is preferably H or lower alkyl having 1 to 4 C atoms and Q ² H. Particularly preferred is Q ¹ = Q ² = H. Furthermore, particular preference is given to compounds of the formula VI in which Q ¹ = H and Q ² 4-cyan -3-fluorophenyl means. In the subsequent ozonolysis, these compounds of the formula VI give a reaction mixture which is particularly easy to work up.

The ozonolysis of the compounds of the formula VI is carried out, as usual, in inert solvents such as carbon tetrachloride, ethyl acetate or in alcohols (especially in Methanol) or acetic acid at low temperatures. The reductive cleavage of the ozonides is preferably carried out with reducing agents such as zinc / acetic acid, trimethylphosphite, sodium dithionite, particularly preferably with dimethyl sulfide or by catalytic hydrogenation, for example on palladium on calcium carbonate.

The fluorobenzene derivatives according to the invention can also be obtained from corresponding aryl oximes [obtainable from the corresponding diazonium salts by reaction with oximes] by hydrolysis according to W. F. Beech, J. Chem. Soc. 1297 (1954) can be obtained in the presence of a copper sulfate / sodium sulfite catalyst.

The intermediates indicated in Scheme 1 are partly new and also the subject of the present invention. Here are in particular the intermediates of the formula

to be mentioned in which R ^{1 is} halogen or OH or their reactive derivatives. The 2-fluorobenzonitrile derivatives of the above formula are particularly preferred.

The present invention also relates to new compounds of the formula A.

wherein R ^{o is} H or straight-chain alkyl having 1 to 7 carbon atoms, p is 1 or 2 and n is 0 or 2. The compounds of the formula A are accessible analogously to EP-OS 0 122 389 from the compounds of the formula I (m = 1 or 2) and are distinguished through a particularly large positive dielectric anisotropy, low viscosity, improved mesophase behavior and favorable elastic properties. The compounds of the formula A according to the invention are very suitable for liquid-crystalline phases in electro-optical display devices.

The following examples are intended to illustrate the invention without limiting it. In the examples, F. is the melting point and K _p . the boiling point of a substance. Percentages above and below mean percentages by weight; all temperatures are given in degrees Celsius. "Conventional work-up" means: water is added, the mixture is extracted with methylene chloride, the mixture is separated off, the organic phase is dried, evaporated and the product is purified by distillation, crystallization and / or chromatography.

example 1

To a slurry of 5.3 g of triphenylmethoxymethylphosphonium chloride in 100 ml of di-isopropyl ether, 1.8 g of solid potassium t-butoxide are added at -15 ° and stirring is continued for 30 minutes. A solution of 2.3 g of 4- (4-cyano-3-fluorophenyl) cyclohexanone [obtainable by reacting 4-bromo-2-fluoro-benzonitrile and cyclohexane-1,4-dione-monoethylene ketal with the slurry is then added to the slurry Butyllithium in ether at -100 ° according to WE Porham and LD Jones, J.Org.Chem. 41, 1187, 2704 (1976), subsequent elimination of water from the cyclohexanol obtained, hydrogenation of the double bond and elimination of the ethylene ketal protective group] in 30 ml of THF and the reaction mixture was stirred for a further 3 hours at room temperature, then poured onto 300 ml of petroleum ether and filtered. The usual work-up of the filtrate gives 4- [4- (methoxymethylene) - cyclohexyl] -2-fluorobenzonitrile as a colorless oil. A mixture of 1.0 g of this oil, 20 ml of THF and 5 ml of 2N Hydrochloric acid is boiled for 30 minutes and then worked up as usual. After crystallization, trans-4- (4-cyano-3-fluorophenyl) cyclohexane carboxaldehyde is obtained.

From 4-bromo-3-fluoro-benzonitrile, analogously, trans- 4- (4-cyano-2-fluorophenyl) cyclohexane carboxaldehyde is obtained.

Example 2

A mixture of 5.0 g of 4-bromo-2-fluorobenzonitrile [obtainable from 4-amino-2-fluorotoluene by conversion into 4-bromo-2-fluorotoluene (K _p ¹² : 55-57 °), subsequent bromination with N- Bromosuccinimide to 4-bromo-2-fluorobenzyl bromide (K ¹ _p ⁴ : 125 - 130 °), subsequent oxidation with dilute

Nitric acid to 4-brora-2-fluoro-benzaldehyde, subsequent

Conversion to 4-bromo-2-fluorobenzaldoxime and subsequent

Conversion to the target product (F. 70 °)], 10 ml of toluene, 10 ml of triethylamine and 0.3 g (PPh ₃ ) ₂ PdBr ₂ was carried out according to RF Heck and A. Schönberg, J.Am.Chem.Soc. 96, 7761 (1974) in an autoclave at 80 at synthesis gas (CO: H ₂ = 1: 1) for 24 hours at 145 °. After cooling and usual work-up, 3-fluoro-4-cyanobenzaldehyde, melting point 83 °, is obtained.

Example 3

To a solution of 11.5 g sodium in 500 ml ethanol, 46 g 2-nitropropane and 107 g 2-fluoro-4-cyanobenzyl bromide [obtained by radical bromination of 2-fluoro-4-cyantoluene, which consists of 2-fluoro- 4-aminotoluene can be obtained by Sandmeyer reaction. Alternatively, 2-fluoro-4-cyahbenzyl bromide is obtained from 2-fluoro-4-bromotoluene by reaction with butyllithium and N-formylpiperidine to give 3-fluoro-4-methylbenzaldehyde, subsequent conversion into oxime and elimination of water]. After 4 hours of stirring, the reaction mixture is filtered, concentrated and worked up as usual. 2-Fluoro-ρ-cyanobenzaldehyde is obtained. Example 4

In a mixture of 13.3 g of 4,4'-dicyan-3,3'-difluorstilbene [obtainable by double Heck reaction from 4-bromo-2-fluorobenzonitrile with ethylene or 4-cyan-3-fluorostyrene according to R.F. Heck, Palladium Catalyzed Vinylation of Organic Halides, Org.React. 27, 345 (1982)] and 150 ml of anhydrous methanol, an equimolar amount of ozone is introduced with stirring at -70 ° within one hour. The ozonide obtained is then split at -70 ° by adding 31.1 g of dimethyl sulfide. The reaction mixture is allowed to warm to room temperature with stirring over the course of 2 hours and is stirred for a further 1 hour. After removal of the solvent, the mixture is worked up as usual. 4-Cyan-3-fluoro-benzaldehyde is obtained.

Example 5

40 g of ethyl ₄ -cyan-3-fluorobenzoate in 40 ml of THF are added dropwise to a solution of 8 g of LiBH ₄ in 120 ml of THF. The reaction mixture comes to a boil. After one hour, it is acidified with 2N HCl and worked up as usual. 3-Fluoro-4-cyanobenzyl alcohol, melting point 70 ° -72 ° C., is obtained.

Example 6

A solution of 22 g of 3-fluoro-4-cyanobenzyl alcohol in 50 ml of methylene chloride is added to 48 g of PCC in 150 ml of methylene chloride with stirring. After one hour, the reaction mixture is mixed with 300 ml of methyl tert-butyl ether and filtered with the addition of Celite. After removal of the solvent and recrystallization from aqueous ethanol, 3-fluoro-4-cyanobenzaldehyde is obtained, mp 83-85 °, IR (cm ^-1 ):

3089, 2880, 2239, 1699, 1571, 1499, 1486, 1428, 1392,

1299, 1251, 1140, 1111, 971, 900, 839, 753;

¹ H NMR (200 MHz): δ (ppm): 7.7-8.0 (m.3H, aromatics), 10.1 (s, 1H, CHO). The following are examples of the use of the fluorobenzene derivatives of the formula I for the production of liquid crystal materials.

Example A

7.4 ml of 1.7 M n-butyllithium in hexane are added to a suspension of 5.4 g of n-butyltriphenylphosphonium bromide in 100 ml of ether with stirring under a nitrogen atmosphere. After 30 minutes, the orange solution is cooled to -40 ° and 2.1 g of 4- (3-fluoro-4-cyanophenyl) cyclohexane-carboxaldehyde in 20 ml of ether are added. After 2 hours of stirring at -40 °, 60 ml of ethanol are added dropwise. The reaction mixture is then allowed to warm to room temperature, stirred for 1 hour and worked up as usual. After conventional isomerization, 2-fluoro-4- [trans-4- (trans-1-pentenyl) cyclohexyl] benzonitrile is obtained analogously to EP-OS 0 122 389.

The following are produced analogously:

2-fluoro-4- [trans-4- (trans-1-propenyl) cyclohexyl] benzonitrile 2-fluoro-4- [trans-4- (trans-1-butenyl) cyclohexyl] benzonitrile

2-fluoro-4- [trans-4- (trans-1-hexenyl) cyclohexyl] benzonitrile

2-fluoro-4- [trans-4- (trans-1-heptenyl) cyclohexyl] benzonitrile Analogous to EP-OS 0 122 389, the following are also produced:

2-fluoro-4- [trans-4- (trans-3-butenyl) cyclohexyl] benzonitrile

2-fluoro-4- [trans-4- (trans-3-pentenyl) cyclohexyl] benzonitrile

2-fluoro-4- [trans-4- (trans-3-hexenyl) cyclohexyl] benzonitrile

2-fluoro-4- [trans-4- (trans-3-heptenyl) cyclohexyl] benzonitrile

Example B

A mixture of 2.3 g of trans-4- (4-cyano-3-fluorophenyl) cyclohexane carboxaldehyde, 1.2 g of 2-propylpropane-1,3-diol, 0.01 g of p-toluenesulfonic acid and 15 ml of toluene is added on Boiled and cooled water separator for 3 hours. After customary working up, 2- [trans-4- (4-cyano-3-fluorophenyl) cyclohexyl] -5-propyl-1,3-dioxane is obtained.

The following are produced analogously:

2- [trans-4- (4-Cyan-3-fluorophenyl) cyclohexyl] -5-ethyl-1,3-dioxane 2- [trans-4- (4-Cyan-3-fluorophenyl) cyclohexyl] -5 -butyl-1,3-dioxane

2- [trans-4- (4-Cyan-3-fluorophenyl) cyclohexyl] -5-pentyl-1,3-dioxane

2- [trans-4- (4-Cyan-3-fluorophenyl) cyclohexyl] -5-hexyl-1,3-dioxane

2- [trans-4- (4-Cyan-3-fluorophenyl) cyclohexyl] -5-heptyl-1,3-dioxane 2- (4-cyano-3-fluorophenyl) -5-ethyl-1,3-dioxane

2- (4-cyan-3-fluorophenyl) -5-propyl-1,3-dioxane, F.49 °, Δε = 31 2- (4-cyan-3-fluorophenyl) -5-butyl-1,3- dioxane 2- (4-cyano-3-fluorophenyl) -5-pentyl-1,3-dioxane 2- (4-cyano-3-fluorophenyl) -5-hexyl-1,3-dioxane 2- (4-cyano- 3-fluorophenyl) -5-heptyl-1,3-dioxane

Example C

A mixture of 2-fluoro-4- (p-pentylphenoxycarbonyl) benzaldehyde (obtainable from 3-fluoro-4-formylbenzoic acid by esterification with p-pentylphenol) and 2-propylpropane-1,3-diol is treated analogously to Example B. 3-Fluoro-4- (5-propyl-1,3-dioxan-2-yl) benzoic acid (p-pentylphenyl ester) is obtained.

The following are produced analogously:

3-fluoro-4- (5-propyl-1,3-dioxan-2-yl) benzoic acid (p-propylphenyl ester)

3-Fluoro-4- (5-propyl-1,3-dioxan-2-yl) benzoic acid (p-ethylphenyl ester)

3-Fluoro-4- (5-propyl-1,3-dioxan-2-yl) benzoic acid (p-ethoxyphenyl ester)

3-fluoro-4- (5-propyl-1,3-dioxan-2-yl) benzoic acid (p-butoxyphenyl ester)

3-fluoro-4- (5-propyl-1,3-dioxan-2-yl) benzoic acid (p-cyanophenyl ester) 3-fluoro-4- (5-propyl-1,3-dioxan-2-yl) benzoic acid (trans-4-ethylcyclohexyl ester)

3-fluoro-4- (5-propyl-1,3-dioxan-2-yl) -benzoic acid (trans-4-propylcyclohexyl ester) 3-fluoro-4- (5-propyl-1,3-dioxan-2- yl) -benzoic acid (trans-4-butylcyclohexyl ester)

3-fluoro-4- (5-propyl-1,3-dioxan-2-yl) benzoic acid (trans-4-pentylcyclohexyl ester)

3-fluoro-4- (5-propyl-1,3-dioxan-2-yl) benzoic acid (trans-4-heptylcyclohexyl ester)

Claims

Claims:

Fluorobenzene derivatives of the formula I.

wherein m is 0, 1 or 2, and their reactive derivatives.

A process for the preparation of the fluorobenzene derivatives of the formula I as claimed in claim 1, characterized in that a compound of the formula II (m = 1 or 2) is used to prepare cyclohexane carboxaldehydes of the formula I (m = 1 or 2)

reacted with triphenylalkoxymethylphosphonium halide in the presence of a base and the alkoxymethylene compound obtained was treated with an acid,

or that for the preparation of benzaldehydes of the formula I (m = 0) a compound of the formula III

in which R ^{1 is} halogen or OH or their reactive derivatives, oxidizes,

or that a compound of formula IV

or that a compound of formula V,

where X is halogen, a monovalent metal or equivalent, formylates,

or that a compound of the formula VI,

treated with ozone and the resulting ozonide reductively cleaves.

3. Use of fluorobenzene derivatives of the formula I according to claim 1 as intermediates in the production of liquid crystal materials.