RU2014317C1 - Method of stereoselective synthesis of z-1,2-diarylallyl chlorides - Google Patents

Abstract

FIELD: organic chemistry. SUBSTANCE: product: Z-1,2-diarylallyl chlorides of the general formula I,

where residues R′ and R″ are independently each of other hydrogen, halogen, alkyl, halogenalkyl, alkoxy, halogenalkoxyoxy or unsubstituted or substituted aromatic residue, and n and m mean 1,2 and 3. Synthesis is carried out by dehydration of chlorohydrines of the general formula II,

Description

_(I) где остатки R¹ и R² независимо друг от друга означают водород/ галоген/ алкил/ галогеналкил/ алкокси/ галогеналкокси или незамещенный или замещенный ароматический остаток/ а n и m означают 1/2 или 3.The invention relates to a stereo selective production of 1/2-diarylallyl chloride of the General formula
(R ¹ )

_(I) where the residues R ¹ and R ² independently of one another are hydrogen / halogen / alkyl / haloalkyl / alkoxy / haloalkoxy or an unsubstituted or substituted aromatic residue / a n and m are 1/2 or 3.

 According to the calculations of Germany NN 3218129 and 3218130 / as well as European patent 196038 and US patent 3422153 / compounds with structure type l are valuable intermediates in obtaining pharmacological / fungicidal and antifungal active principles. Until now, they have been prepared by radical halogenation of the corresponding diarylpropene compounds or by oxidation followed by a substitution reaction. A disadvantage of the methods known from the prior art is the use of expensive reagents (for example / such expensive halogenation reagents) as N-bromosuccinimide in the radical bromination reaction / number of synthesis reaction steps and / in particular / low stereo selectivity of the reaction.

 It is well known that molecules / exhibiting a specific biological or pharmacological action / in many cases require a certain geometric arrangement of certain functional groups. For example, among the fungicidal active principles, compounds with a Z configuration (especially the sequence of substituents according to Kahn / Ingold and Prelog) are especially effective as plant protection agents / i.e. compounds / in which unsubstituted or substituted phenyls have one relative to the other are in a trans position.

 Therefore, the objective of the present invention was to develop a method / according to which it is possible to obtain intermediate products 1 with a maximum yield with maximum isomer purity / i.e. with high selectivity for the E- and trans-configuration of phenyl residues / compounds attached to the double bond. Another objective was / to use profitable intermediates to develop a method for producing fungicidal azolylmethyloxiranes IV / characterized by high overall yields and fewer reaction steps / than the known methods.

 According to the prior art, aryl-substituted alcohols under acidic reaction conditions (for example) using sulfuric acid in the organic phase can be converted to the corresponding aryl-substituted olefins or styrenes (see / for example / Houben-Weyl, Methoden der organischen Chemie, 4th ed. / T. 5/1 b Alkene, Cycloalkene, Arylalkene publishing house Georg Thieme Verlag Stuttgart / 1972 / p. 62 and f. / In particular p. 70 and 71; Tetrahedron v. 26. p. 4277 f. ( 1790 g)).

 It is also known / that a similar kind of reaction can be carried out using water acceptors / for example acetanhydride. However, high temperatures are usually required to carry out these cleavage reactions. Under such reaction conditions, only an insufficient ratio of the E and Z isomers with respect to the position of the aryl relative to the aryl is obtained.

где остатки R¹ и R² независимо друг от друга означают водород/ галоген/ алкил/ галогеналкил/ алкокси/ галогеналкокси или незамещенный или замещенный ароматический остаток/ а n и m означают 1/2 или 3/ отличающийся тем/ что хлоргидрины формулы II

CH

где остатки имеют вышеуказанное значение/ дегидратируют в инертном растворителе/ представляющем собой простой эфир или сложный эфир карбоновой кислоты/ в присутствии ангидрида карбоновой кислоты или органической кислоты или неорганической кислоты или олеума при температурах до 50^°С.A method has now been found for the stereo-selective preparation of Z-1/2-diaryl-allyl chlorides of the general formula I
(R ¹ )

where the residues R ¹ and R ² independently from each other mean hydrogen / halogen / alkyl / halogenated / alkoxy / halogenated or unsubstituted or substituted aromatic residue / a n and m mean 1/2 or 3 / characterized in that the chlorohydrins of the formula II

CH

where the residues have the above meaning / dehydrate in an inert solvent / representing an ether or carboxylic acid ester / in the presence of carboxylic anhydride or organic acid or inorganic acid or oleum at temperatures up to 50 ^° C.

 According to the proposed method / high stereo selectivity of 1/2-diarylallyl chloride with Z-configuration is ensured. Typically / in particular when implementing preferred embodiments of the proposed method, the ratio Z: E is 8: 1 to 15: 1. The regioselectivity / with which the removal of water proceeds is unexpectedly high / because it could be expected / that, as a side reaction, the reaction of water cleavage to the side of the chloromethyl side chain to the formation of chlorovinyl diaryl compounds will proceed to an increased extent. Further / it is possible to suppress such expected competing reactions / as a water substitution reaction instead of its removal. The expected acylation of the alcohol group is also virtually absent.

Cl+XMg

CH

II
Что касается способа получения Z-аллилхлоридов целесообразно провести реакцию дегидратации отдноступенчатым способом/ т. е. получить сначала хлоргидрин в простом диэтиловом эфире и добавить к полученному диэтилэфирному раствору неорганическую кислоту/ например/ конц.серную/ и ангидрид карбоновой кислоты при температуре ок. 10-0^°С.Chlorohydrins of the general formula II are well known and can be obtained with good inputs (for example) by the addition of Grignard IV benzyl compounds to ω-chloroacetophenones VII according to the following reaction scheme:

Cl + XMg

CH

II
As for the method for producing Z-allyl chlorides, it is advisable to carry out the dehydration reaction in a one-step way / i.e., first obtain chlorohydrin in diethyl ether and add inorganic acid to the obtained diethyl ether solution (for example / sulfuric acid) and carboxylic anhydride at a temperature of approx. 10-0 ^° C.

 In addition, / chlorohydrin can be obtained not only in the form of an aqueous solution as a result of the above synthesis / but also by isolating it from its previous stage / i.e. from magnesium alkoxylate as a result of the addition of equimolar amounts of acid (for example sulfuric acid) followed by dehydration.

 According to the invention / it is advisable to gradually add carboxylic acid anhydride / and the process of O-acylation of chlorohydrin can be largely suppressed in favor of the dehydration process.

10^°C можно добавить незначительные количества апротонных растворителей/ например этилацетата/ галогенуглеводородов/ таких как метиленхлорид или ТГФ/ например к диоксану в качестве растворителя.The proposed dehydration reaction of chlorohydrins II is carried out in ether or complex as a solvent. In the case of the use of non-cyclic ethers, preference should be given to esters with the number of oxygen atoms of at least 2 / for example esters of glycols and low molecular weight aliphatic alcohols / for example ethylene glycol dimethyl or-diethyl ether. Cyclic ethers (for example, THF and, in particular, dioxane) have proven particularly advantageous. To improve solvolysis at low temperatures / for example / below

At 10 ^° C, minor amounts of aprotic solvents can be added (e.g. ethyl acetate / halogenated hydrocarbons) such as methylene chloride or THF / e.g. dioxane as a solvent.

от 10:1 до 1:10. В целях достижения высоких выходов за единицу времени и высоких долей Z-изомеров рекомендуется прибавить добавки в количествах 5-20 мас.% считая на диоксан.For the proposed method, esters of low molecular weight aliphatic carboxylic acids (in particular monocarboxylic) with low molecular weight aliphatic alcohols were found to be particularly advantageous esters / wherein the concept of low molecular weight alcohols includes alcohols with the number of C atoms from one to six. Examples of esters are acetic acid ethyl ester / formic acid ethyl ester / propionic acid methyl ester / butyric acid methyl ester / isobutyric acid methyl or ethyl ester / with ethyl acetate being preferred. Amounts of solvents do not play a decisive role and vary widely. they usually comprise 1-50 wt.% / in particular 2 / 5-10 wt.% / counting on chlorohydrin II. Higher amounts of solvents are possible. For dehydration, you can also use a mixture of solvents / mentioned / for example / in paragraph 1-5 of the claims / and the ratio of the components can vary widely

from 10: 1 to 1:10. In order to achieve high yields per unit time and high proportions of Z-isomers, it is recommended to add additives in amounts of 5-20 wt.% Based on dioxane.

 As an acid acceptor, carboxylic anhydride is added to the reaction mass. In particular, such anhydrides of aliphatic low molecular weight monocarboxylic acids / such as acetic anhydride / propionic / butyric and isobutyric acids are used. But you can also use anhydrides of aliphatic or aromatic dicarboxylic acids / for example malonic / maleic / succinic or phthalic acids.

 In the dehydration reaction (as a rule) 0 / 5-3 / in particular 1-2 molar equivalents of anhydride are used / counting on chlorohydrin II. The use of large quantities is also possible / but they do not provide any additional benefits.

 Particularly advantageous results are achieved by combining dioxane and / or THF as a solvent and acetic anhydride and sulfuric acid, or when ethyl acetate is used as a solvent in combination with isobutyric acid anhydride and sulfuric acid.

 Dehydration is carried out under acidic reaction conditions / using conventional acids / for example, organic sulfonic acids / such as trifluoromethanesulfonic / methanesulfonic / p-toluenesulfonic or naphthalenesulfonic / and in particular concentrated mineral acids / such as perchloric / phosphoric and in particular sulfuric with a concentration of 30- 99/9% / preferably 50-99% / or oleum. In the case of acids with a high water content, a larger amount of carboxylic acid anhydride is usually used.

 The acid is used in a catalytic / stoichiometric or excess amount / counting on compound II. Amounts of about 0 / 01-4 mole are preferred. equivalent / counting on compound II. In the case of the use of oleum, it is advisable to use smaller amounts - 0 / 05-1 molar equivalent / counting on compound II.

 An advantageous embodiment of the present invention consists in the fact that instead of a carboxylic acid anhydride, ketene as such or in combination (counting on compound II) with stoichiometric or catalytic amounts of aliphatic carboxylic acid is used as an acceptor of water. In this case, it is advisable to place a carboxylic acid in the reactor (for example, one of the aforementioned low molecular weight aliphatic) and add gaseous ketene to the reaction mass or add ketene in gaseous form to the chlorohydrin II dissolved in the solvent without the addition of carboxylic acid. The amount of ketene added corresponds to the above amounts of carboxylic acid anhydride.

50^°С/ предпочтительно от -25 до +40^°С/ в частности от - 25 до +30^°С.To achieve high proportions of Z-isomers, it is recommended to carry out dehydration at minimum temperatures / i.e. at temperatures up to

50 ^° C / preferably from -25 to +40 ^° C / in particular from -25 to +30 ^° C.

 Generally / dehydration is carried out under normal pressure. The reaction under high or low pressure is also possible and an increase in pressure in some cases can lead to an increase in output per unit time.

где остатки R¹ и R² независимо друг от друга означают водород/ галоген/ алкил С₁-С₇/ галогеналкил С₁-С₅ алкокси С₁-С₅/ галогеналкокси С₁-С₅ или незамещенный или замещенный одним- тремя остатками/ указанными для радикалов R¹ и R²/ ароматический остаток;
n-1 или 2/ или 3.Thus / according to the proposed method / get Z-1/2-diarylallyl chloride of the formula I

where the residues R ¹ and R ² independently from each other mean hydrogen / halogen / alkyl C ₁ -C ₇ / halogenated C ₁ -C ₅ alkoxy C ₁ -C ₅ / haloalkoxy C ₁ -C ₅ or unsubstituted or substituted by one to three residues / indicated for the radicals R ¹ and R ² / aromatic residue;
n-1 or 2 / or 3.

In the formula I, the indices n and m preferably mean 1 / a and the substituents R ¹ and R ² in this formula are independently hydrogen / halogen / for example fluorine / chlorine / bromine / iodine / preferably chlorine and fluorine; branched or unbranched C ₁ -C ₇ alkyl / e.g. methyl / ethyl / propyl / 1-methylethyl / butyl / 1-methylpropyl / 2-methylpropyl / 1/1-dimethylethyl / pentyl / 1-methylbutyl / 2-methylbutyl / 3-methylbutyl / 1/1-dimethylpropyl / 1/2-dimethylpropyl / 2/2-dimethylpropyl / 1-ethylpropyl / hexyl / 1-methylpentyl / 2-methylpentyl / 3-methylpentyl / 4-methylpentyl / 1/1-dimethylbutyl / 1/2 -dimethylbutyl / 1/3-dimethylbutyl / 2/2-dimethylbutyl / 2/3-dimethylbutyl / 3/3-dimethylbutyl / 1-ethylbutyl / 2-ethylbutyl / 1/1/2-trimethylpropyl / 1/2/2 / - trimethylpropyl / 1-ethyl-1-methylpropyl / 1-ethyl-2-methylpropyl;
haloalkyl C ₁ -C ₆ / e.g. fluoromethyl / difluoromethyl / trifluoromethyl / chlorodifluoromethyl / dichlorofluoromethyl / trichloromethyl / 1-fluoroethyl / 2-fluoroethyl / 2/2-difluoroethyl / 2/2/2-trifluoroethyl / 2-chloro-2 / 2- difluoroethyl / 2/2-dichloro-2-fluoroethyl / 2/2/2-trichloroethyl / pentafluoroethyl / preferably trifluoromethyl;
alkoxy C ₁ -C ₅ / e.g. methoxy / ethoxy / propoxy / 1-methylethoxy / butoxy / 1-methylpropoxy / 2-methylpropoxy / 1/1-dimethylethoxy / preferably methoxy / ethoxy and propoxy:
haloalkoxy C ₁ -C ₅ / e.g. difluoromethoxy / trifluoromethoxy / chlorodifluoromethoxy / dichlorofluoromethoxy / 1-fluoroethoxy / 2-fluoroethoxy / 2/2-difluoroethoxy / 1/1/2/2-tetrafluoroethoxy / 2/2/2-trifluoroethoxy / 2- chloro-1/1/2-trifluoroethoxy / pentafluoroethoxy / preferably trifluoromethoxy;
an aromatic residue / for example phenyl / which is unsubstituted or one- / two- or threefold substituted by the residue R ³ / having a preferred meaning / indicated for R ¹ or R ² / i.e. which means hydrogen / halogen / branched or unbranched alkyl C ₁ -C ₇ / haloalkyl C ₁ -C ₆ / alkoxy C ₁ -C ₅ / or haloalkoxy C ₁ -C ₅ .

Residues R ¹ -2-F and R ² -2-Ce are preferred.

 Compared to the known from DE-A 3218 129 Z-1/2-diarylallyl bromides / Z-1/2-diarylallyl chlorides of the general formula I, there are unexpected advantages. In addition to their very simple epoxidation to diaryloxyranes, one should also mention the advantage that due to the stereoselectivity of epoxidation, not mixtures of oxirane isomers are obtained (which is the case) when the starting material is known Z-1/2-diarylallyl bromides / and oxiranes / in which aryls have a transoidal arrangement.

There may be / for example / the types of substitution indicated in Table 1:
Determination of the ratio of Z: E isomers in diarylallyl chlorides I is carried out in a known manner / for example, by HPLC (high-speed liquid chromatography) / gas chromatography or by ¹ H-NMR spectrometry using pure Z and E isomers for comparison and standardization of the corresponding ratios of isomeric components of the mixture.

 Obtaining fungicidal active principles III and IV on the basis of starting materials - diarylallyl chlorides I and chlorohydrins II is depicted in the following reaction scheme.

I

Последовательность реакций согласно синтезу б) можно осуществить известным образом/ например по методу/ принцип которого описан в патенте ДЕ-А 3218129. Реакция замещения хлорного атома азольной или имидазольной группой в соединении V обычно осуществляется в инертном растворителе/ например диметилформамиде или N-метилпирролидоне/ в присутствии неорганического или органического основания/ такого как гидроксид натрия или калия/ карбоната натрия или калия/ дициклогексиламина/ диметилциклогексиламина.

I

The reaction sequence according to synthesis b) can be carried out in a known manner / for example by the method / the principle of which is described in patent DE-A 3218129. The substitution reaction of a chlorine atom with an azole or imidazole group in compound V is usually carried out in an inert solvent (for example dimethylformamide or N-methylpyrrolidone) the presence of an inorganic or organic base / such as sodium or potassium hydroxide / sodium or potassium carbonate / dicyclohexylamine / dimethylcyclohexylamine.

Intermediates V are new compounds. Preferred residues R ¹ and R ² / as well as indices n and m have a meaning / similar to the definitions / set forth in connection with the description of compound I (see table 2).

 In the case of synthesis a) the first stage / i.e. the substitution step corresponds to the last synthesis step b). It is advisable to carry out the dehydration process and the subsequent process of substitution in a one-stage method without isolation and purification of the intermediate product II. In order to epoxidize compounds III, it is advisable to use a high excess of supra-maleic acid / which is obtained in situ by reacting 5-30 mole equivalents / in particular 5-10 mole%. eq. maleic anhydride / counting on compound III / with a hydrogen peroxide solution in amounts below stoichiometric / counting on maleic anhydride. Usually a molar ratio of anhydride to hydrogen peroxide of 1 / 5-10 / in particular 2-4 is used. Preferably, a 30-50% aqueous solution of hydrogen peroxide is used.

The reaction temperature for the epoxidation process is 0-100 ^° C / in particular 20-80 ^° C.

 Epoxidation is carried out in the presence of an aprotic polar solvent. As such solvents, you can use / for example / such halogenated hydrocarbons / as dichloromethane / dichloroethane / chlorobenzene or chlorotoluene / or aromatic hydrocarbons / such as benzene / toluene or xylene. The amount of solvent is not critical. It is usually 5-50 / in particular 10-20 wt.% / Counting on the olefin.

 According to this method of epoxidation / you can get much higher yields of azolylmethyloxiranes IV / than by the method / described in patent DE-A 3218129.

 The individual synthesis steps are described in the following examples.

 Example 1. Obtaining starting materials II.

 1-Chloro-2- (4-chlorophenyl) -3- (2-chlorophenyl) propan-2-ol.

2-6^°С реакционную массу по каплям добавляют в 1/5 л конц. раствора хлористого аммония. После экстрагирования метил-трет-бутиловым эфиром с последующей обычной переработкой получают 92/9 г (выход 99%/ степень чистоты по данным ВСЖХ - 68/2 %) 1-хлор-2-(4-хлорфенил)-3-(2-хлорфенил)пропан-2-ол в виде сырого масла/ которое подвергается последующей реакции. Для определения продукта проводили перекристаллизацию из н-гексана; т.пл. 64-69^°С.To 9/7 g (0/404 mol) of magnesium shavings in 20 ml abs. diethyl ether at 24-36 ^° C over 5 minutes add 5/0 g (0/031 mol) of 2-chlorobenzyl chloride. After the reaction begins, a solution of 200 ml is added dropwise. abs of diethyl ether and 50/2 g (0/31 mol) of 2-chlorobenzyl chloride. Then continue to heat the mass at reflux for another 10 minutes In a nitrogen atmosphere, excess magnesium is decanted. The resulting Grignard solution was placed in a reactor at 0 ^° C. Then 55/7 g (0/3 mol) of n-chloro-ω-chloroacetophenone (dissolved in 350 ml of toluene) was added dropwise and the mass was continued to mix at 0 ^° C for another 1/5 h. At temperature

2-6 ^{° C. the} reaction mass is added dropwise in 1/5 L conc. ammonium chloride solution. After extraction with methyl tert-butyl ether, followed by normal processing, 92/9 g (yield 99% / purity according to HPLC 68/2%) 1-chloro-2- (4-chlorophenyl) -3- (2- chlorophenyl) propan-2-ol as a crude oil / which undergoes a subsequent reaction. Recrystallization from n-hexane was performed to determine the product; so pl. 64-69 ^° C.

 Examples 2-5 and comparative examples I-IV.

 Chlorohydrin Dehydration II.

 Z-3-chloro-2- (4-chlorophenyl) -1- (2-chlorophenyl) propene.

 (Compound N 1.16 in table 1).

At −2 ^° C., to 60 g (0/2 mol) of chlorine alcohol (described in Example 1), 24/5 g (0/24 mol) of acetanhydride are added to 230 ml of dioxane and 23 ml of THF. Then, 2/36 g (0/024 mol) conc. Are added dropwise to the mass. sulfuric acid. After stirring for 3 hours at 0 ^°, according to the LCLC, virtually all of the starting material reacted.

Then, at 0 ^° C, a mixture of a half-saturated solution of sodium chloride and a 50% sodium hydroxide solution is added over 30 minutes in order to establish a pH value of 8-9.

 Finally, the organic phase is dried and concentrated in vacuo / after which it can be used for subsequent reactions without any further purification.

Yield 55/7 (ZE = 9.1 / 1) of crude oil / which, after recrystallization from n-hexane, gives a pure Z-isomer with mp 79-82 ^° C.

 Similarly, it is possible to obtain Z-1/2-diarylallyl chlorides (See table 1).

 Z-3-chloro-2- (4-fluorophenyl) -1- (2-chlorophenyl) propene.

(examples N 1/6 in table 1)
1-chloro-2- (4-fluorophenyl) -3- (2-chlorophenyl) -propen-2-ol / obtained by the Grignard addition of 2-chlorobenzylmagnesium chloride to p-fluoro-ω-chloroacetophenone and used as a crude material with the degree of purity according to HPLC 78-87% / under the reaction conditions / described in table 2 / was subjected to reaction / as described in example 2. The proportion of Z- and E-isomers was determined by high-speed liquid chromatography (unadjusted relative percentage of area) (see table 3).

 Dehydration of 1-chloro-2- (4-fluorophenyl) propan-2-ol.

H

____→

Пример 6. Получение хлоргидрина и процесс дегидратации "ин ситу" 1-хлор-2-(4-хлорфенил)-3-(2-хлорфенил)пропан-2-ол.F

H

____ →

Example 6. Obtaining chlorohydrin and the process of dehydration in situ 1-chloro-2- (4-chlorophenyl) -3- (2-chlorophenyl) propan-2-ol.

A solution of 170 g (1/0 mol) of 2-chlorobenzyl chloride in 400 ml of diethyl ether is added dropwise to 36/0 (1/5 mol) of magnesium chips in 200 ml of diethyl ether. Then, a solution of 155 g (0/9 mol) of p-fluoro-ω-chloroacetophenone in 450 ml of diethyl ether is added dropwise at -10 ^{° C.} Then, an additional 2 hours are stirred at 25 ^° C.

Then, 49/0 g (0/5 mol) of conc. Sulfuric acid in 300 ml of diethyl ether are added dropwise at -10 ^{° C.} Then they are heated to 25 ^° C and sucked off from the precipitated salt. The resulting crude ethereal solution of chlorohydrin is used for the reaction below.

 Z-3-chloro-2- (4-fluorophenyl) -1- (2-chlorophenyl) propene.

To 525 ml of the above crude solution / containing approx. 134/5 g of chlorohydrin (0/45 mol) / at -10 ^° C add 8/0 g (0/08 mol) of conc. Hydrochloric acid / after which 57/1 g (0/58 mol) is added over 2 hours acetanhydride. Then the precipitated salt is again separated by filtration. The crude allyl chloride obtained by evaporation of the solvent from the filtrate is used for trisol substitution or for epoxidation.

 Example 7. Ketene option.

 Z-3-chloro-2- (4-fluorophenyl) -1- (2-chlorophenyl) propene.

1 ч пропускают 43 г (1/02 моль) кетена. После обычной переработки продукта на основе данных ВСЖХ получают выход/ который практически равняется выходу/ получаемому в случае применения ацетангидрида в соответствии с примером 2. Соотношение Z- и Е-изомеров для данного типа ведения реакции составляет

11:1.At 0 ^° C, 250 ml of dioxane / 25 ml of THF / 12/4 g of acetic acid (0/2 mol) and 69 g (0/23 mol) of crude 1-chloro-2- (4-fluorophenyl) -3 - (2-chlorophenyl) propan-2-ol / obtained by the Grignard reaction of example 1 / for

43 g (1/02 mol) of ketene are passed in for 1 hour. After the usual processing of the product, on the basis of the LCLC data, a yield is obtained (which is practically equal to the yield) obtained in the case of using an anhydride in accordance with Example 2. The ratio of Z and E isomers for this type of reaction is

11: 1.

Examples 8 and 9. Obtaining azolylmethyloxyranes IV in the synthesis of a)
Z-3- (1/2/4-triazol-1-yl) -2- (4-chlorophenyl) -1- (2-chlorophenyl) propene.

70^° до тех пор/ пока не образуется прозрачный раствор. Затем охлаждают до 10^°С/ после чего в течение 1 ч по каплям добавляют 49/5 г полученного по примеру 2 Z-3-хлор-2-(4-хлорфенил)-1-(2-хлорфенил)пропен в виде сырого продукта в 50 мл диметилформамида. Затем массу перемешивают еще 4 ч при комнатной температуре.To a solution of 11/5 g (0/17 mol) of triazole in 150 ml of dimethylformamide, 6/6 g of sodium hydroxide is added and heated to stirring to a temperature

70 ^° until / until a clear solution forms. Then it is cooled to 10 ^° C / after which 49/5 g of the Z-3-chloro-2- (4-chlorophenyl) -1- (2-chlorophenyl) propene obtained in the form of a crude product are added dropwise over a period of 1 h over the course of 1 h. in 50 ml of dimethylformamide. Then the mass is stirred for another 4 hours at room temperature.

Then 200 ml of water are added and extracted repeatedly with methyl tert-butyl ether. The collected organic phases are washed / dried and concentrated in vacuo. Recrystallization from methyl tert-butyl ether and n-hexane gives
24/4 g of Z-3- (1/2/4-triazol-1-yl) -2- (4-chlorophenyl) -1- (2-chlorophenyl) propene with so pl. 106-110 ^° C.

 Cis -2- (1/2/4-triazol-1-ylmethyl) -2- (4-fluorophenyl) -3- (2-chlorophenyl) oxirane.

84 g (0/9 mol) of maleic acid anhydride and 6 drops conc. sulfuric acid in 90 ml of dichloroethane, together with 22 g of 50% hydrogen peroxide, is heated to 50 ^° C. Then, 28 g (0/089 mol) of Z-3- (1/2/4-triazol-1-yl) are added dropwise. ) -2- (4-fluorophenyl) -1- (2-chlorophenyl) propene in 75 ml of dichloroethane. The mass is stirred for 3 hours at the indicated temperature and then another 2/5 hours at 70 ^° C.

After cooling the reaction mass, the product is sucked off from precipitated maleic acid and shaken with a solution of thiosulfate and a dilute solution of sodium hydroxide. The organic phase dried and maximally evaporated in vacuo at a temperature of about 50 ^° С after cooling and repeated evaporation of the mother liquor gives 14 g of the target product (which equals a yield of 50%).

 Examples 10 and 11.

 Obtaining azolylmethyloxyranes IV according to synthesis b).

 Cis-1-chloromethyl-2- (2-chlorophenyl) -1- (4-fluorophenyl) oxirane (compound N 2.6 in Table 2).

Starting from 56/2 g (0/2 mol) of Z-3-chloro-2- (4-fluorophenyl) -1- (2-chlorophenyl) propene in 530 ml of glacial acetic acid and 196 g (2 mol) of maleic anhydride are added acids. Then, 68 g (1 mol) of a 50% hydrogen peroxide solution are added over 1 hour at 25 ^{° C.} The mass is stirred for another 3-4 hours at 40 ^° C / then for 10 hours at 25 ^° C.

Finally, the reaction mass with stirring is introduced into 3 l of water and 50 ml of a 10% sodium thiosulfate solution and then, if necessary, the sodium thiosulfate solution is added again until the peroxide disappears. The resulting colorless precipitate is sucked off and dried. The crude material / obtained by recrystallization from p-hexane can be used without purification (mp. 68-70 ^° C).

 Cis-2- (1/2/4-triazol-1-ylmethyl) -2- (4-fluorophenyl) -3- (2-chlorophenyl) oxirane.

1/5 g (5 mmol) of cis-1-chloromethyl-2- (2-chlorophenyl) -1- (4-fluorophenyl) oxirane and 0/69 g (75 mmol) of 1/2/4-sodium triazolid 5 hours at 75 ^° C in 7 ml of DMF. After cooling, the reaction mass is neutralized by adding a small amount of acetic acid (after which about 10 ml of water is added), as a result, a crystalline product precipitates (1/4 g yield). The resulting product is sucked off / washed with water and dried in vacuo.

Claims (9)

1. METHOD FOR STEREO SELECTIVE PRODUCTION OF Z-1,2-DIARYLALLYL CHLORIDES of the general formula
(R ₂ )

where R ₁ and R ₂ independently from each other - hydrogen, halogen, alkyl, halogenated, alkoxy, halogenated or unsubstituted or substituted aromatic residue;
n and m = 1,2 or 3,
characterized in that the chlorohydrins of the General formula

where R ₁ and R ₂ have the indicated meaning,
dehydrate in an inert ether or carboxylic acid ester as a solvent in the presence of carboxylic anhydride or the corresponding ketene and organic or inorganic acid or oleum at temperatures up to 50 ^o C.  2. The method according to claim 1, characterized in that the solvent used is a simple cyclic ether or a low molecular weight ester of aliphatic carboxylic acid.  3. The method according to claim 1, characterized in that the anhydride of aliphatic monocarboxylic acids is taken as the carboxylic acid anhydride.  4. The method according to claims 1 to 3, characterized in that the dehydration is carried out in dioxane and / or tetrahydrofuran as a solvent in the presence of acetanhydride and sulfuric acid.  5. The method according to claims 1 to 3, characterized in that the dehydration is carried out in ethyl acetate, as a solvent in the presence of isobutyric acid anhydride and sulfuric acid.  6. The method according to claim 1, characterized in that ketene is used, if necessary, in combination with organic carboxylic acid in an amount from catalytic to stoichiometric, based on the chlorohydrin of the specified formula. 7. The method according to claim 1, characterized in that the dehydration is carried out at a temperature of from -25 to +30 ^o C.  8. The method according to claim 1, characterized in that the dehydration is carried out in the presence of 0.01 to 4.0 mol of sulfuric acid and 0.5 to 3.0 mol of carboxylic anhydride.  9. The method according to claim 1, characterized in that the dehydration is carried out in the presence of 0.05 to 1.0 mol of oleum in a mixture with 1 to 2 mol of carboxylic anhydride.

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