DE4012865A1 - Fluoro-aryl cpds. prodn. with ortho electrophilic substituent - Google Patents

Abstract

Prodn. of ortho-substd. fluoroaryl cpds. (I) comprises adding a strong base to a mixt. of a fluoroaryl cpd. and an electrophile. Also claimed is the use of o-fluoroarylboric acids, esters and anhydrides (I) i) for prodn. of corresp. o-fluorophenols by oxidative hydrolysis; ii) for prodn. of corresp. o-fluorohaloaryl cpds. by halogenation; or iii) as coupling components in transition metal cross-coupling reactions with halo- and perfluoroalkylsulphonyl cpds. Pref. cpds. (I) have the formula (I) R1 = H,F, alkyl, alkenyl or alkoxy with up to 18C or a mesogenic gp., W,X,Y = N, CH or CF; E = -CH2-R2, -CH(OH)-R2, -CH2-CH(OH)-R2 or a gp. of the formula (ii), (iii), (iv), (v), (vi) or (vii) R2 = 1-15C alkyl or a mesogenic gp. R3,R4 = H or alkyl, alkenyl or cycloalkyl with up to 10C or R3+R4 = -(CH2)n- or -CH2-CHR8-CH2-; R5 = aliphatic, cycloaliphatic, araliphatic or aromatic gp., R8 = alkyl, alkoxy or alkenyl with up to 18C or a mesogenic gp. Z = gp. of formula (VIII) n = 2-4.

Description

The invention relates to a process for alkylation or hydroxyalkylation of fluorinated aromatics in ortho- Position on the fluorine atom, taking one out of a mixture the fluorinated aromatic and the alkylation or Hydroxyalkylating agent adds a strong base.

Fluorinated aromatics, which are ortho to the F atom alkylated or hydroxyalkylated are significant Intermediates in organic industrial chemistry. Correspondingly substituted derivatives are in particular valuable intermediates for the synthesis of highly refined End products or even such end products for the Electronic industry, such as B. liquid crystals for Plant protection, such as B. pesticides or for production of pharmaceutically highly effective substances, such as. B. Dopamine receptor blockers, antiemetics or antipsychotics, represents.

The processes for the preparation of these described so far Connections are not suitable for industrial use Production, but represent processes that are only can be carried out safely on a laboratory scale.  

So you get z. B. in the D.L. Ladd in J. Org. Chem. 46, 203 (1981) described metalation of 1,4-difluorobenzene with butyllithium at <-65 ° C 1-lithium-2,5-difluorobenzene, that at the same (lower) temperature with trimethyl borate converted to 2,5-difluorobenzeneboronic acid dimethyl ester becomes.

The boronate is formed by oxidation with hydrogen peroxide the corresponding phenol.

This reaction sequence is also in WO 89/2425 Preparation of the 2,3-difluorophenol described, wherein the reaction temperatures not and the reaction conditions little changed:

Furthermore, the production of liquid crystalline 2,3- or 2 ', 3'-difluoro-p-terphenylene starting from 1,2-difluorobenzene. In the WO 89/8629 is the representation of other others liquid crystalline compounds which contain a 2,3-difluoro Have 1,4-phenylene group described. In the processes described there, 1,2-difluorobenzene or 1-substituted-2,3-difluorobenzene with a  strong base, usually deprotonated with n-butyllithium and the 2,3-difluorophenyllithium compound obtained with implemented an electrophile.

Furthermore, the o-fluorophenyl derivatives can be obtained from the corresponding o-fluorobromobenzenes by reaction with Magnesium to o-fluorophenyl magnesium bromide and subsequent Produce derivatization (e.g. EP 02 38 272). Here too it is imperative to work at low temperatures.

The reason for the low reaction temperatures is in the low stability of the o-fluorophenyllithium or -Magnesium compounds. In particular 2,3-difluorophenyllithium Derivatives split lithium fluoride above -50 ° C starting with 1-fluoro-2,3-gasoline derivatives, which react uncontrollably to unknown secondary products.

At -50 ° C is the rate of the decomposition reaction of the 2,3-difluorophenyllithium derivatives still low, however, it is explosive at -25 ° C (critical Temperature -22.5 ° C), the 2,3-difluorophenyllithium Suddenly decompose derivatives.

Such a synthesis can of course only be done on a small scale be carried out in the laboratory. For larger approaches this process is not used in production plants Question because if the coolant fails, the equipment becomes a potential bomb.

Due to recent developments in the electronics industry there has been a significant need for liquid crystals, which is a single or multiple fluorinated 1,4-phenylene radical, in particular a 2,3-difluoro or 2,6-difluoro Have 1,4-phenylene. The satisfaction of this need  using the previously known methods is an unsolvable task because it is carried out without risk this low-temperature reaction on a large scale is not guaranteed is. The object of the present invention was a To find production processes for o-fluorophenyl derivatives, this describes the disadvantages of the previous methods does not have and is risk-free on an industrial scale Scale is to be carried out.

It has now been found that the desired reaction Surprisingly, can be made "safe" if you have the Reaction partner addition mode changes: When presenting the Fluoroaryl derivative and the alkylating or hydroxyalkylating agent in an inert solvent and Drop of butyllithium or other strong drops Base is intermediate o-fluoroaryllithium Connection immediately in situ from the alkylating or hydroxyalkylating agent intercepted and cannot accumulate and thus lead to dangerous side reactions. This is surprising because butyllithium and z. B. Lithium diisopropylamide itself with the alkylation or Hydroxyalkylating agents can react and therefore not with the emergence of the o-fluorophenyl derivatives could be expected.

The invention thus relates to a method for Alkylation or hydroxyalkylation of fluorinated Aromatics ortho to the fluorine atom, characterized in that that you get to a mixture of the fluorinated Aromatics and the alkylating or hydroxyalkylating agent admits a strong base, especially a process for the alkylation or hydroxyalkylation of fluorinated Aromatics of formula I,  

in which

R 1 H, F, alkyl, alkenyl, alkoxy each having up to 18 carbon atoms or a mesogenic group,
W, X and Y are each independently N, CH or CF

mean.

Such methods are in particular the subject of the invention, wherein R¹ is a mesogenic group of the formula II, in which

R⁰-A¹-Z¹ - (- A²-Z²-) _m - (II)

R⁰ is an unsubstituted or a simply substituted by CN, halogen or CF₃ alkyl or alkenyl radical having up to 15 carbon atoms, in which radicals one or more CH₂ groups are each independently of one another by -S-, -O-, -CO -, -CO-O-, -O-CO- or -O-CO-O- can be replaced so that S and / or O atoms are not directly linked,
Z¹ and Z² each independently of one another -CH₂CH₂-, -C≡C-, -CH₂O-, -OCH₂-, -CO-O-, -O-CO-, -CH = N-, -N = CH-, -CH₂S -, -SCH₂-, a single bond or an alkylene group with 3 to 6 carbon atoms, in which a CH₂ group is replaced by -O-, -CO-O-, -O-CO-, -CHHalogen- or -CHCN- can be, and
A¹ and A² each independently

• (a) trans-1,4-cyclohexylene radical, in which also one or more non-adjacent CH₂- Groups replaced by -O- and / or -S- could be,
• (b) 1,4-phenylene radical, in which also one or two CH groups must be replaced by N. can,
• (c) radical from the group 1,3-cyclobutylene, 1,3-bicyclo (1,1,1) pentylene, 1,4-cyclohexenylene, 1,4-bicyclo (2,2,2) octylene, Piperidine-1,4-diyl, naphthalene-2,6-diyl, Decane hydronaphthalene-2,6-diyl and 1,2, 3,4-tetrahydronaphthalene-2,6-diyl,

where the residues (a) and (b) by CN or halogen can be substituted, and

m 0, 1 or 2

mean.

Those produced by the process according to the invention o-fluoroaryl derivatives include mono-, di-, tri- and tetra- Fluorophenyl derivatives and pentafluorophenyl derivatives.  

In addition, according to the inventive method 2-fluoropyridin-3-yl derivatives can be prepared. Whether alongside the fluorine substituents further substituents on the aromatic Ring is in place when performing the The method according to the invention is not critical. As another Examples of substituents are alkyl, alkenyl or alkoxy groups, halogens such as chlorine and bromine or called mesogenic groups. In addition, the fluorinated aromatic rings are also components of condensed Be ring systems, such as. B. of naphthalenes, di- and tetrahydronaphthalenes or of 2,3,4,5-tetrahydro-1H-3-benzazepine Derivatives.

For the sake of simplicity, Phe in the following means a 1,4-phenylene group, where also one or two CH groups are replaced by N. can be, with a 1,4-phenylene group also by one or two halogen atoms can be substituted, ArF one fluorinated 1,4-phenylene group of the formula

where L¹, L² and L³ are each independently H or F mean.

Cy is a trans-1,4-cyclohexylene radical, in which also one or several non-adjacent CH₂ groups replaced by -O- could be.

E means a group which is characterized by the alkylation or hydroxyalkylation reaction was introduced.

Preferred alkylation or hydroxyalkylation reagents are the compounds of formula IIIa to IIIf:

wherein R² is alkyl having 1 to 16 carbon atoms or one of the formula II means corresponding mesogenic group and X¹ Cl, Br, iodine or a perfluoroalkyl sulfonic acid group means.

The compounds produced by the process according to the invention of formula I include those of formulas IVa to IVg

Of these, the compounds of the formulas IVa, IVb, IVd and IVg are particularly preferred. In the connections mentioned of the formulas IVa to IVg, R 1 is preferably H, alkyl or alkoxy each having 1 to 12 carbon atoms or a mesogenic The rest, particularly preferred according to the invention Process the compounds of formula IVb, wherein R¹ H or alkoxy with 1 to 12, in particular with 2 to 4 carbon atoms means. These are particularly suitable as Intermediates for the production of liquid crystals with a 2,3-difluoro-1,4-phenylene or 2,3-difluoro-1,4- phenyleneoxy structural unit. The compounds of formula IV which have a mesogenic radical of the formula II accordingly the compounds of the formulas IV1 to IV13:

R⁰-A¹-ArF-E (IV1)

R⁰-A¹-Z¹-ArF-E (IV2)

R⁰-A¹-A²-ArF-E (IV3)

R⁰-A¹-A²-Z²-ArF-E (IV4)

R⁰-A¹-Z¹-A²-ArF-E (IV5)

R⁰-A¹-Z¹-A²-Z²-ArF-E (IV6)

R⁰-A¹-A² - ArF-E (IV7)

R⁰-A¹-Z¹-A²-ArF-E (IV8)

R⁰-A¹-A²-Z²-A²ArF-E (IV9)

R⁰-A¹-A²-A²-Z²-ArF-E (IV10)

R⁰-A¹-Z¹-A²-Z²-A²-ArF-E (IV11)

R⁰-A¹-Z¹-A²-A²-Z²-ArF-E (IV12)

R⁰-A¹-A²-Z²-A²-Z²-ArF-E (IV13)

These include the compounds of the formulas IV1, IV2, IV3, IV4 and IV7 particularly preferred.

Of the compounds of the formulas IV1, those of the Formulas IV1a to IV1c are particularly preferred.

Alkyl-Phe-ArF-E (IV1a)

Alkyl-Cyc-ArF-E (IV1b)

Alkoxy-Phe-ArF-E (IV1c)

Of the compounds of formula IV2, those of Formulas IV2a to IV2i are particularly preferred

Alkyl-Phe-CH₂CH₂-ArF-E (IV2a)

Alkyl-Phe-CH₂O-ArF-E (IV2b)

Alkyl-Phe-C≡C-ArF-E (IV2c)

Alkoxy-Phe-C≡C-ArF-E (IV2d)

Alkoxy-Phe-CH₂O-ArF-E (IV2e)

Alkoxy-Phe-CH₂CH₂-ArF-E (IV2f)

Alkyl-Cyc-CH₂CH₂-ArF-E (IV2g)

Alkyl-Cyc-CH₂O-ArF-E (IV2h)

Alkyl-Cyc-C≡C-ArF-E (IV2i)

In the preferred compounds of the above and below Formulas R¹ is an alkyl group with preferably 1 to 10 carbon atoms, an alkoxy or an alkenyl group preferably each having 1 to 10 carbon atoms.

Particularly preferred alkyl groups are hexyl, pentyl, Butyl, i-butyl, propyl, i-propyl, methyl and ethyl, in particular Methyl; are particularly preferred alkoxy groups Hexoxy, pentoxy, i-butoxy, propoxy, i-propoxy, methoxy and ethoxy, especially methoxy; particularly preferred Alkenyl groups are hexenyl, pentenyl, butenyl and allyl.

In the preferred compounds of the above and below Formulas can be the alkyl radicals, in which also a CH₂ group (alkoxy or oxaalkyl) replaced by an O atom can be straight-chain or branched. Preferably do you have 2, 3, 4, 5, 6, 7, 8, 9 or 10 C- Atoms and therefore preferably denote ethyl, propyl, butyl, Pentyl, hexyl, heptyl, octyl, nonyl, decyl, propoxy, Ethoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, nonoxy or decoxy, also undecyl, dodecyl, undecoxy, Dodecoxy, 2-oxapropyl (= 2-methoxymethyl), 2- (= ethoxymethyl) or 3-oxabutyl (= 2-methoxypentyl), 2-, 3- or 4-oxapentyl, 2-, 3-, 4- or 5-oxahexyl, 2-, 3-, 4-, 5- or 6-oxaheptyl.

A¹ and A² are preferably Cyc or Phe. In the connections of the formulas above and below preferably means Phe one 1,4-phenylene (Ph), one or two 1,4-phenylene group (PheX) substituted by F or CN a pyrimidn-2,5-diyl- (pyr), a pyridine-2,5-diyl- (Pyn), a pyrazine-3,6-diyl or a pyridazine-2,5- diyl group, particularly preferably Ph, PheX, Pyr or Pyn. Preferably contain those according to the invention Processes produced connections no more than one  1,4-phenylene group, wherein one or two CH groups through N are replaced. Cyc preferably means a 1,4-cyclohexyl group. However, compounds are particularly preferred of formula I, wherein one of the groups A¹ and A² a 1,4- substituted by CN in the 1- or 4-position Cyclohexylene group means and the nitrile group in axial position, d. H. the group A² or A² has the following configuration:

Compounds of the formula I and are particularly preferred of the preceding sub-formulas, which are a grouping -Phe-Phe- included. -Phe-Phe- is preferably -Ph-Ph-, Pyr-Phe or Ph-Pyn. The groups are particularly preferred

as well as unsubstituted or one or more times Fluorine-substituted 4,4'-biphenylyl.

Compounds of the formula I are particularly preferred and the sub-formulas below, which are 2,3-difluoro 1,4-phenylene group included.

The groups Z¹ and Z² each mean independently of one another preferably a single bond, secondarily preferably -C≡C- or -CH₂CH₂ - groups. Particularly preferred are compounds of the formulas I in which a group Z¹-CH₂CH₂- means.  

Compounds of the formulas above and below with branched ones Wing groups R¹ can be important. Branched groups of this type usually do not contain more than two chain branches. R1 is preferred a straight-chain group or a branched group with no more than a chain branch.

Preferred branched radicals are isopropyl, 2-butyl (= 1-methylpropyl), isobutyl (= 2-methylpropyl), tert.- Butyl, 2-methylbutyl, isopentyl (= 3-methylbutyl), 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2-ethylhexyl, 5-methylhexyl, 2-propylpentyl, 6-methylheptyl, 7-methyloctyl, isopropoxy, 2-methylpropoxy, 2-methylbutoxy, 3-methylbutoxy, 2-methylpentoxy, 3-methylpentoxy, 2-ethylhexoxy, 1-methylhexoxy, 1-methylheptoxy, 2-oxa- 3-methylbutyl, 3-oxa-4-methylpentyl.

The rest R¹ can also be an optically active organic Rest with an asymmetric carbon atom. The asymmetric carbon atom is then preferably included two differently substituted carbon atoms, one hydrogen atom and a substituent selected from the group fluorine, alkyl or linked alkoxy each having 1 to 5 carbon atoms and CN. The optically active organic radical R preferably has Formula,

wherein

X ′ -O-, -S- or a single bond,
Q ′ alkylene with 1 to 5 C atoms, in which a CH₂ group which is not linked to X ′ can also be replaced by -O-, or a single bond,
Y 'CN, F, CF₃, methyl or methoxy, and
R⁷ is an alkyl group other than Y ′ with 1 to 15 C atoms, in which one or two non-adjacent CH₂ groups can also be replaced by -S-, -O-,

means.

X 'is preferably a single bond.
Q 'is preferably -CH₂-, -CH₂CH₂-, -CH₂CH₂CH₂- or a single bond, particularly preferably a single bond.
Y 'is preferably CH₃, -CN or F, particularly preferably CN or F.
R⁷ is preferably straight-chain or branched alkyl or alkoxy having 1 to 10, in particular having 1 to 7, carbon atoms.

Among the compounds of formula IV and IVa to IVg are preferred those in which at least one of them is included contained residues one of the preferred meanings indicated Has.

The compounds of formula I required as starting materials

in which R 1, W, X and Y have the meaning given, are known or are made according to methods known per se,  as described in the literature (e.g. in the Standard works such as Houben-Weyl, methods of organic Chemie, Georg-Thieme-Verlag, Stuttgart), namely under Reaction conditions for the reactions mentioned are known and suitable. You can also start from well-known variants not mentioned here Make use.

The implementation of the process of the invention is simple, taking the starting materials at temperatures from -100 ° to 100 ° C, preferably -40 ° to 40 ° C, in particular 0 ° to 35 ° C, and with increased or decreased Can implement pressure, preferably at normal pressure.

A major advantage of the method according to the invention compared to that known from the prior art The fact that you can not at low temperatures (-100 ° to -65 ° C) must work to prevent explosive decomposition to prevent o-fluorophenyllithium at higher temperatures, since this is only formed in situ and by the existing alkylating or hydroxyalkylating agents is always intercepted.

The fluorinated aromatics are expediently placed in the Mixture with the alkylating or hydroxyalkylating agent in an inert solvent and gives the strong base. The reaction can be without or beneficial be carried out in the presence of an inert solvent, where as solvents with strong bases come into consideration, e.g. B. ethers such as diethyl ether, tetrahydrofuran or methyl tert-butyl ether, hydrocarbons such as pentane, hexane, Heptane, benzene, toluene, xylene or cyclohexane or mixtures of the solvents mentioned. These solvents can also cosolvents, such as. B. Hexamethylphosphoric triamide (HMPT), tetramethylethylenediamine (TMEDA), dimethylpropyleneurea (DMPU) or crown ethers such as 18-Crown-6  will. The amount of solvent is not critical generally 100 to 1000 g of solvent per mole fluorinated aromatic compound can be used.

As an alkylating agent or hydroxyalkylating agent come the compounds of the formulas IIIa to III into consideration, preferably with n-alkyl halides 1 to 16 carbon atoms, especially n-alkyl bromides and iodides, such as B. methyl, ethyl, propyl, butyl, pentyl, Hexyl, heptyl, octyl or nonyl bromide or methyl, Ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl or nonyl iodide, n-alkanals with 2 to 16 carbon atoms, in particular Acetaldehyde, propionaldehyde, butyraldehyde, pentanal, Hexanal, Heptanal, Octanal or Nonanal, Oxinane such as B. oxirane, 2-methyloxirane, 2-ethyloxirane, 2-propyloxirane, 2-butyloxirane, 2-pentyloxirane, 2-hexyloxirane or 2-heptyloxirane.

The type of strong base to be used depends on the fluorinated aromatics used. Particularly suitable strong bases are alkali metals such as lithium, sodium or Potassium, alkali metal hydrides such as lithium, sodium or Potassium hydride, alkaline earth metal hydrides such as calcium hydride, organometallic compounds, such as n-butyllithium, sec.- Butyllithium, tert-butyllithium, methyl lithium, ethyl lithium or phenyllithium, especially n-butyllithium, strong amide bases such as sodium amide, potassium amide, lithium diisopropyl amide, Lithium cyclohexyl isopropylamide, lithium dicyclohexylamide, 2,2,6,6-tetramethylpiperidin-1-yllithium, Lithium hexamethyldisilazane or potassium hexamethyldisilazane, especially lithium diisopropylamide.

Another advantage of the method according to the invention lies in that it is safely interrupted at all times and later can be resumed since during the dropping  the base only unreactive compounds, such as the fluorinated Aromat, the alkylating or hydroxyalkylating agent, Metal alcoholate and the o-fluoroaryl derivative are present.

In a preferred embodiment of the invention The process involves placing the fluoroaromatics together with approximately 10-80%, especially 15-25%, of the alkylation to be used or hydroxyalkylating agent in an inert Solvent, preferably tetrahydrofuran, before and there the base, preferably under an inert gas atmosphere Lithium diisopropylamide, in an inert solvent along with the remaining amount of the alkylation or hydroxyalkylating agent (20-90%, preferably 75 to 85%).

As a rule, you need 1 mol of the deprotonated product Fluorine atoms 0.8 to 2.2 mol, preferably 1.2 to 1.8 moles of base and 0.8 to 1.5 moles, preferably 1.0 to 1.3 moles of alkylating or hydroxyalkylating agents.

Working up the reaction mixture and isolation the products are made in the usual way, e.g. B. by doing that Reaction mixture on water and / or ice or diluted Pouring acid and after separating the aqueous phase o-fluoroarylboronic acid derivative by distillation or Crystallization wins.

According to the method according to the invention, it is surprising possible, the o-fluoroaryl derivatives, the valuable intermediates for example for liquid crystals, auxiliaries, Pesticides and pharmaceuticals are in versus State of the art simple, safe, in large To produce scale and in higher yields.  

The ¹H nuclear magnetic resonance spectra are recorded with a 200 MHz spectrometer from Bruker.

Example 1 Preparation of 1- (4′-pentylbiphenyl-4-yl) -2- (3,5-difluoro- 4-propylphenyl) ethane

A solution of lithium diisopropylamide (0.02 mol) in THF / Hexane made from 0.02 mol diisopropylamide in 25 ml THF and 12.5 ml of a 1.6 molar solution of n-butyllithium in hexane, dropwise becomes a mixture at 25 ° C of 0.02 mol of 1- (4'-pentylbiphenyl-4-yl) -2- (3,5- difluorophenyl) ethane, 0.02 mol N, N-dimethylpropylene urea, 0.02 mol of 1-iodopropane and 25 ml of THF. To The reaction mixture is stirred for 1.5 hours at room temperature poured onto water, the phases are separated and the aqueous phase was extracted with 2 × 50 ml of methylene chloride. After drying over magnesium sulfate, evaporation of the solvent and chromatography you get that pure product.

The following are produced analogously:

Example 2 Preparation of 2- (4'-propylbicyclohexyl-4-yl) -1- (2,6- difluoropyridin-3-yl) ethane

A solution of 0.02 mol lithium diisopropylamide in THF / Hexane (produced analogously to Example 1) is at 25 ° C. dropwise to a mixture of 0.2 mol of 2,6-difluoropyridine, 0.02 mol N, N-dimethylethylene urea, 0.02 mol 2- (4'-Propylbicyclohexyl-4-yl) -1-iodoethane and 25 ml Given THF. After stirring for 1.5 hours and working up this is obtained as described in Example 1 pure product.

The following are produced analogously:

Claims (7)

1. A process for the alkylation or hydroxyalkylation of fluorinated aromatics ortho to the fluorine atom, characterized in that a strong base is added to a mixture of the fluorinated aromatics and the alkylating or hydroxyalkylating agent. 2. The method according to claim 1 for the alkylation or hydroxyalkylation of fluorinated aromatics of the formula I, where R1 is H, F, alkyl, alkenyl, alkoxy each having up to 18 carbon atoms or a mesogenic group,
W, X and Y each independently represent N, CH or CF. 3. The method according to claim 2, characterized in that R¹ is a mesogenic group of the formula II, wherein R⁰-A¹-Z¹ - (- A²-Z²-) _m - (II) R⁰ is an unsubstituted or simply by CN, halogen or CF₃ substituted alkyl or alkenyl radicals with up to 15 carbon atoms, one or more CH₂ groups in these radicals each independently of one another by -S-, -O-, -CO-, -CO-O-, -O- CO- or -O-CO-O- can be replaced so that S and / or O atoms are not directly linked to one another,
Z¹ and Z² each independently of one another -CH₂CH₂-, -C≡C-, -CH₂O-, -OCH₂-, -CO-O-, -O-CO-, -CH = N-, -N = CH-, -CH₂S -, -SCH₂-, a single bond or an alkylene group with 3 to 6 carbon atoms, in which a CH₂ group is replaced by -O-, -CO-O-, -O-CO-, -CHHalogen- or -CHCN- can be, and
A¹ and A² each independently

• (a) trans-1,4-cyclohexylene radical, in which one or more non-adjacent CH₂ groups can also be replaced by -O- and / or -S-,
• (b) 1,4-phenylene radical, in which one or two CH groups can also be replaced by N,
• (c) residue from the group 1,3-cyclobutylene, 1,3-bicyclo (1,1,1) pentylene, 1,4-cyclohexenylene, 1,4-bicyclo (2,2,2) octylene, piperidine-1 , 4-diyl, naphthalene-2,6-diyl, decane hydronaphthalene-2,6-diyl and 1,2,3,4-tetrahydronaphthalene-2,6-diyl,

where the residues (a) and (b) by CN or halogen can be substituted, and m means 0, 1 or 2. 4. The method according to any one of claims 1 to 3, characterized characterized in that the reaction in an inert Performs solvent. 5. The method according to any one of claims 1 to 4, characterized characterized in that the reaction temperature between -40 ° and + 40 ° C. 6. The method according to any one of claims 1 to 5, characterized characterized in that one as a strong base organometallic compound or an alkali metal amide starts.