Z-1,2-Diaryl-allyl chlorides

The invention relates to diarylalkylchlorides applied as intermediates in the process of obtaining compounds with pharmacologically active fungicidal and antifungal properties.

It is well-known that compounds that exhibit specific or pharmacological actions in many cases depend on the specific geometric location of certain functional groups. For example, among the active phyticidal agents or particularly high activity as plant protection remedies, they possess, first of all, compounds with Z configuration (see Can, Inhold and Prelog rule) of consecutive substitutions, ie compounds in which unsubstituted or substituted phenyls. is in position - trans with respect to each other.

Intermediate compounds obtained by radical halogenation of the corresponding diarylpropenic compounds [1], [3], [4] or by acidification with subsequent substitution reaction [2], which do not possess such a configuration, are known.

According to the prior art the aryl-substituted alcohols under the acidic conditions of the reaction, for example with the application of sulfuric acid in the organic medium, may be transferred to the corresponding aryl-substituted olefins or styrene.

It is also known that similar reactions can be performed using the acceptor! of water, for example, acetanhydride. However, high temperatures are usually required for decomposition reactions. Under these conditions, there is insufficient ratio of E- and Z-isomers to the location of the aryl to the double bond.

The problem solved by the present invention is to obtain the most active Z-isomer, which does not confine impurities with the E-isomer.

The compounds of formula (I) having the Z configuration of the phenolic residues as opposed to the pure state double bond were not known.

Thus, according to the present invention, Zl, 2-diarylalkyl chlorides of formula I are proposed

<img file="MD1255C2_D0001.tif" />

<img file="MD1255C2_D0002.tif" />

wherein R¹ and R² independently of one another represents hydrogen, halogen, lower alkyl, lower halogenalkyl, lower alkoxy, halogen lower alkoxy, phenyl, unsubstituted or substituted by halogen, halogen-lower alkyl; n and m mean 1, 2 or 3.

The technical result consists in obtaining the Z-isomer with a high degree of purity.

Z-1,2-diarylalkylchlorides of general formula (I) are obtained by dehydration of hydrochlorides of formula P1

<img file="MD1255C2_D0003.tif" />

wherein R¹ and R², n and m have the value indicated above, in an inert solvent, which represents a carbonic acid ether or ester in the presence of carbonic anhydride or an organic or inorganic acid at up to 50 ° C.

The process provides high stereoselectivity for obtaining 1,2-diarylalkylchloride with Z-configuration. As a rule, when making the preferred variants of performing the proposed process, the Z: E ratio constitutes 8: 1-15: 1. It is surprisingly high and also the regioselectivity, with which the water removal occurs, because it can be predicted that as an adiphonal reaction to a more intensive extent the reaction of water decomposition in the direction of the chloromethyl side chain will take place, forming chlorvinyl diaryl compounds. Subsequently, concurrent reactions such as the substitution reaction of the water instead of its removal can be suppressed. The expected acylation of the alcoholic group is also effectively absent.

The hydrochlorides of the general formula Π are well known and can be obtained, for example, according to the revetments DE 2851086 A, EP 47594 A or EP 15757 A with good yields of the reaction reaction of the Griniar VI benzyl compounds with the VH ω-chloro-acetophenones according to the following scheme. of the reaction:

(R)

<img file="MD1255C2_D0004.tif" />

+ XMg- CH ₂·

VH

VI (x = Cl, Br)

Regarding the process for obtaining Z-allyl chlorides, it is rational to perform the dehydration reaction through a stepwise process, that is to say, in the beginning, hydrochloride is obtained in diethyl ether and in the obtained diethyl etheric solution, inorganic acid, for example, concentrated sulfur is added. , and carbon dioxide anhydride at -10-0 ° C.

In addition, hydrochloride can be obtained not only in the form of a hydric solution as a result of the synthesis described above, but also by eliminating it from the preceding stage, ie from magnesium alkoxylate by adding equimolar amounts of acid, for example, sulfuric acid, with subsequent dehydration.

According to these processes, it is rational to gradually add carbonic anhydride, making it possible to significantly suppress the process of O-acylation of hydrochloride to the advantage of the dehydration process.

The proposed dehydration reaction of the hydrochlorides П is carried out in an ether or ester as a diluent. In the case of the use of non-cyclic ethers preferentially! are ethers with at least 2 oxygen atoms, for example, low molecular weight glycols and aliphatic alcohols, for example ethylene glycodimethyl or diethyl ether. Particularly advantageous have been found to be cyclic ethers, for example, THF and in particular dioxane. In order to improve solvolysis at low temperatures, for example, lower than about 10 ° C, insignificant amounts of aprotonic diluents, for example, ethylacetate, halogen hydrocarbons such as methylchloride or THF, for example dioxane can be added. of thinner.

For the present process, particularly advantageous esters have been proved to be the ethers of aliphatic low-molecular-weight carbonic acids, in particular monocarbonic ones, with low-molecular-weight aliphatic alcohols, the notion of low-molecular-weight alcohols containing alcohols having the number of atoms. of C from one to six. Examples of ethers may be called acetic acid ethyl ether, formic acid ethyl ether, propionic acid methyl ether, butyric acid methyl ether, isobutyric acid methyl or ethyl ether, preferably ethylacetate.

The quantities of diluents do not play a dominant role and vary widely. They, as a rule, are about 1-50% by weight, in particular 2.5-10% by weight, calculating for hydrochloride П. Larger quantities of thinners are also possible. For dehydration, the diluent mixtures mentioned in, for example, in claims 1-5 of the present invention may also be used, the ratio of the components having the possibility to vary within wide limits, from 10: 1 to 1:10. In order to achieve high yields per unit of time and high parts of Z-isomers, it is recommended to add an additive in quantities of 5-20% by weight, calculating for dioxane.

As a water acceptor in the reaction mass, carbon dioxide anhydride is added. In particular, such anhydrides of low molecular weight aliphatic monocarbonic acids such as acetanhydride, propionic, butyric and isobutyric acid anhydride are applied. However, the anhydrides of aromatic dicarbonic acids can also be used! or aliphatic, for example, malonic, maleic, succinic or phthalic acids.

In the dehydration reaction, usually, 0.5-3, in particular, 1-2 molar equivalents of anhydride are used, calculating for hydrochloride II. It is also possible to use large quantities, but they do not give any additional benefits.

Particularly advantageous results are obtained by combining dioxane and / or THF as diluent and acetanhydride and sulfuric acid or, in the case of using ethyl ether, acetic acid as diluent in combination with isobutyric acid anhydride and sulfuric acid.

Dehydration is performed under acidic reaction conditions, for the creation of which ordinary acids are used, for example, such organic acids! of sulfur, such as trifluoromethanesulfonic, methanesulfonic, para-toluenesulfonic or naphthalenesulfonic, and in particular mineral acids! Concentrates, such as chlorine, phosphorus, and in particular sulfur, with a concentration of 30-99.9%, preferably 50-99%, or oleum. In the case of using acids with a higher water content, as a rule, a greater quantity of carbon dioxide anhydride is used.

The acid is used in a catalytic, stehiometric or surplus quantity, calculating for the compound П. There are preferably quantities of about 0.01-4 molar equivalents, calculating for the compound П. In the case of using the oil, it is rational to use smaller quantities, 0.05-1 molar equivalents, calculating for the compound П.

The advantageous embodiment of the present process consists in the fact that as a water acceptor instead of carbonic anhydride, the actual ketene is used or in combination, calculating for the compound П, with stehiometric or catalytic quantities of aliphatic carbonic acid. In this case it is rational to place in the reactor carbonic acid, for example, an aliphatic one with a low molecular weight of the ones mentioned above, and adding in the reaction mixture of the gaseous ketene or in the dilute hydrochloride in the diluent is added the gaseous ketene without additive of carbonic acid. The amount of ketene added corresponds to the aforementioned quantities of carbon dioxide anhydride.

In order to achieve high Z-isomers it is recommended to perform dehydration at minimum temperatures, ie at temperatures up to about 50 ° C, preferably being -25- + 40 ° С, in particular -25 + 30 ° C. '

Dehydration is usually performed under normal pressure. Carrying out the reaction under high or low pressure is also possible and raising the pressure in some cases may lead to an increase in yield in a unit of time.

Z-1,2-Diarylalkylchlorides, obtained according to the process described, having general formula I:

<img file="MD1255C2_D0005.tif" />

wherein R¹ and R², independently of one another, represents hydrogen, halogen, C1-7 alkyl, C15 halogenalkyl, C1-5 alkoxy, C1.5 halogenalkoxy or aromatic radical unsubstituted or substituted by one to three residues, indicated for R radicals¹ and R², and n equal to 1, 2 or 3 are also an object of the present invention.

In formula I the indices n and m, preferably, represent 1. Substitutions R¹ and R² In this formula, independently of each other, it represents, in particular, hydrogen;

halogen, for example, fluorine, chlorine, bromine, iodine, preferably, chlorine and fluorine;

C1-7 branched or unbranched alkyl, for example, methyl, ethyl, propyl, 1-methylethyl, butyl, 1methylpropyl, 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; C1-6 halogenalkyl, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chlordifluoromethyl, dichlorfluoromethyl, 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;

C 1-5 alkoxy, for example, methoxy, ethoxy, propoxy, 1-methylethoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy, 1,1-dimethylethoxy, preferably methoxy, ethoxy and propoxy;

C1-5 halogenalkoxy, for example, difluoromethoxy, trifluoromethoxy, chlordifluoromethoxy, dichlorfluoromethoxy, 1-fluoroethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 2,2,2-trifluoroethoxy, 2- chloro1,1,2-trifluoroethoxy, pentafluoroethoxy, preferably trifluoromethoxy;

aromatic residue, for example, phenyl unsubstituted or substituted once, two, three times by R³, which has a preferential value, indicated for R¹ or R²ie, hydrogen, halogen, branched or unbranched C 1-6 alkyl, C 1-6 alkyl, C 1-5 alkoxy or C 1-5 halogenalkoxy.

I'm preferably R¹ which represents 2-F and R² which represents 2-C1.

Compared to Zl, the 2-diarylalkyl chlorides known in DE 3218129 A; A-1,2-diarylalkyl chlorides of general formula I have surprising advantages. In addition to their very simple epoxidation up to the diariloxiranes of general formula V, it should be mentioned that that, due to the stereoselectivity of the epoxidation, no mixtures of oxirane isomers are obtained, which occurs when the starting material is Zl, 2-diarylalylbromides. known, but the oxiranes, whose arils have a transoidal location.

There may be types of substitution indicated, for example, in Table 1:

<img file="MD1255C2_D0006.tif" />

Table 1

<td>Nr. compound</td><td>(R) N</td><td>(R²) m</td><td>Ttop. (° C), 1H-RNM (ppm)</td>

<td> 1.1</td><td>3-C1</td><td>3-C1</td><td></td>

<td> 1.2</td><td>4-C1</td><td>2,4-dichloro</td><td></td>

<td> 1.3</td><td>4-F</td><td>2-СНз</td><td></td>

<td> 1.4</td><td>4-F</td><td>2-CF3</td><td></td>

<td> 1.5</td><td>H</td><td>2-OCF3</td><td></td>

<td> 1.6</td><td>4-F</td><td>2-C1</td><td> 66</td>

<td> 1.7</td><td>4-OCH₃</td><td>2-C1</td><td></td>

<td> 1.8</td><td>4-Br</td><td>2,4-dichloro</td><td></td>

<td> 1.9</td><td>4-СбН₅-СН₂О</td><td>3-СНз</td><td></td>

<td> 1.10</td><td>4-p-CLC₆H4</td><td>2-C1</td><td></td>

<td> 1.11</td><td>П-С4Н9</td><td>2-C1</td><td></td>

<td> 1.12</td><td>4-C₆H₅</td><td>2,4-dichloro</td><td></td>

<td> 1.13</td><td>4-F</td><td>3-CF₃</td><td></td>

<td> 1.14</td><td>4,5-dichloro</td><td>2-СНз</td><td></td>

<td> 1.15</td><td>4-C₆H₅A</td><td>2-C1</td><td></td>

<td> 1.16</td><td>4-C1</td><td>2-C1</td><td> 79-82</td>

Determination of the ratio of Z: E isomers in diarylalkylchlorides I is performed in a manner known, for example, by CLVM (high-speed liquid chromatography), by gas chromatography or by spectrometry-1H-RNM, by applying Z- and E-. pure isomers for comparing and standardizing the corresponding ratios of isomeric components of the mixture.

Obtaining the active fungicidal agents Ш and IV based on the starting materials, being diarylalkyls I and hydrochloride П, is reproduced in the reaction scheme, presented below:

<img file="MD1255C2_D0007.tif" />

synthesis a) ⁺

<img file="MD1255C2_D0008.tif" />

epoxidation synthesis

<img file="MD1255C2_D0009.tif" />

<img file="MD1255C2_D0010.tif" />

permalic acid anhydride synthesis b)

<img file="MD1255C2_D0011.tif" />

<img file="MD1255C2_D0012.tif" />

<img file="MD1255C2_D0013.tif" />

-HCl

<img file="MD1255C2_D0014.tif" />

<img file="MD1255C2_D0015.tif" />

The reactions according to synthesis b) can be carried out in a known manner, for example, the hippie which is described in the patent DE 3218129 A. The reaction of substitution of the azole or imidazolic ointment in compound V, is usually quoted in the diluent _t dimethylformamide or N-methylpyrrolidone in the presence of the inorganic base or

Consecutively by the process, the inert clove atom, which is essentially organic, such as sodium or potassium hydroxide, sodium or potassium carbonate, dicyclohexylamine, dimethylcyclohexylamine.

The preferential residues R1 and R2 of the intermediate products V, as well as the indices n and m, have the values ​​analogous to those shown in the description of compound I. For example, there are types of substitution shown in table 2:

<img file="MD1255C2_D0016.tif" />

<img file="MD1255C2_D0017.tif" />

Table 2

<td>Nr. compound</td><td>(R) N</td><td>(R²) m</td><td>Ttop. (° C), 1H-RNM (ppm)</td>

<td> 2.1</td><td>3-C1</td><td>3-C1</td><td></td>

<td> 2.2</td><td>4-C1</td><td>2,4-dichloro</td><td></td>

<td> 2.3</td><td>4-F </td><td>2-СНз</td><td></td>

<td> 2.4</td><td>4-F</td><td>2-CF₃</td><td></td>

<td> 2.5</td><td>H</td><td>2-OCF3</td><td></td>

<td> 2.6 </td><td>4-F</td><td>2-C1</td><td> 68-70</td>

<td> 2.7</td><td>4-ОСНз</td><td>2-C1</td><td></td>

<td> 2.8</td><td>4-Br</td><td>2,4-dichloro</td><td></td>

<td> 2.9</td><td>4-C₆H₅CH₂A</td><td>З-СН3</td><td></td>

<td> 2.10</td><td>4-p-CLC₆H4</td><td>2-C1</td><td></td>

<td> 2.11</td><td>П-С4Н9</td><td>2-C1</td><td></td>

<td> 2.12</td><td>4-C₆H₅</td><td>2,4-dichloro</td><td></td>

<td> 2.13</td><td>4-F</td><td>3-CF3</td><td></td>

<td> 2.14</td><td>4,5-dichloro</td><td>2-СНз</td><td></td>

<td> 2.15</td><td>4-C₆H₅A</td><td>2-C1</td><td></td>

<td> 2.16</td><td>4-C1</td><td>2-C1</td><td></td>

In the case of synthesis a) the first stage, ie the substitution stage, corresponds to the last stage of synthesis b). It is rational to perform the dehydration process and the subsequent process of substitution by a one-step process without eliminating and purifying the intermediate product П.

For the purpose of the epoxidation of the HI compounds it is rational to use the large excess of extramaleic acid, which is obtained in situ by the interaction of 5-30, in particular 5-10 molar equivalents of maleic anhydride, calculating for the HI compound, with the hydrogen peroxide solution. in quantities smaller than the stehiometric ones, calculating for maleic acid anhydride. Usually, the molar ratio of anhydride with hydrogen peroxide of 1.5-10 is used, in particular of 2-4. Preferably a hydrogen peroxide water solution with a concentration of 30-50% 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 polar aprotonic diluent. As such diluents, for example, halogen hydrocarbons, such as dichloromethane, dichloromethane, chlorobenzene or chlortoluene, or such aromatic hydrocarbons as benzene, toluene or xylene, may be used. The amount of diluent is not decisive. Usually, it constitutes 5-50, in particular 10-20 percent by weight, calculating for olefin.

According to this epoxidation process, considerably higher yields of azolylmethyloxyrane IV can be obtained than according to the process described in patent DE 3218129 A.

The separate stages of the synthesis are described in the following examples.

Example 1

Obtaining Initial Substances of P-Chloro-2- (4-Chlorophenyl) -3- (2-Chlorophenyl) Propane-2-ol

To 9.7 g (0.404 moles) of magnesium tar in 20 ml of absolute diethyl ether at 24-36 ° C for 5 minutes add 5.0 g (0.031 moles) of 2-chlorobenzylchloride. After starting the reaction, 200 ml of absolute diethyl ether solution and 50.2 g (0.31 moles) of 2-chlorobenzylchloride are added dropwise. Then continue heating the mass to the deflection temperature for another 10 minutes. In the atmosphere of nitrogen the excess magnesium is decanted. The resulting Griniar solution is placed in a reactor at 0 ° C. Then 55.7 g (0.3 moles) of para-chloro-o-chlorcetophenone, diluted in 350 ml of toluene, are added dropwise and the mixture is stirred at 0 ° C for a further 1.5 hours. At a temperature of about 2-6 ° C the reaction mass is added dropwise in 1.5 l of concentrated solution of chlorinated ammonia. After extraction with tertiary methylbutyl ether, 92.9 g (99% yield, purity according to CLVI data is 62.8%) obtained from 1 chloro-2- (4-chlorophenyl) -3 (2-chlorophenyl). ) propane-2-ol in the form of crude oil, which itself is subject to the subsequent reaction. To determine the product, recrystallization from n-hexane was performed.

Melting temperature: 64-69 ° C.

Examples 2-5 and comparison examples I-IV

Hydrochloride dehydration П

Z-3-Chloro-2- (4-Chlorophenyl) -1 - (2-Chlorophenyl) propene (Compound No. 1.16 according to Table 1)

At -2 ° C in 60 g (0.2 moles) of chlorinated alcohol, as described in Example 1, in 230 ml of dioxane and 23 ml of THF add 24.5 g (0.24 moles) of acetanhydride. Then 2.36 g (0.024 moles) of concentrated sulfuric acid are added dropwise to the mass. After mixing for 3 hours at 0 ° C according to the CLVI data, effectively all the starting material reacted.

Then at 0 ° C for 30 minutes add a mixture of obtained chlorinated sodium solution and caustic sodium solution with a concentration of 50% to establish the 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 further purification.

The yield is 55.7 g (Z / E = 9, l / 1) of crude oil, which after recrystallization from n-hexane gives a pure Z-isomer with Ttop. from 79-82 ° C.

Analogously, Zl, 2-diarylalkylchlorides can be obtained according to table 1.

Z-3-Chloro-2- (4-fluorophenyl) -1 - (2-chlorophenyl) propene (Example No. 1.6 according to Table 1) 1-Chloro-2- (4-fluorophenyl) -3- (2-chlorophenyl) -propane-2-ol, obtained by Griniar's binding reaction of 2-chlorobenzylmagnesium chlorinated with para-fluoro-o-chloracetophenone and applied as a raw material with the degree of purity according to the CLVÎ data of 78-87 ° C, in the reaction conditions described in Table 2 were subjected to the reaction, as described in Example 2. The part of Z- and E-isomers was determined by the high-speed liquid chromatography procedure (the relative percentage of surface corrected).

'Table 3

Dehydration of 1-chloro-2- (4-fluorophenyl) propane 2-ol

F

<img file="MD1255C2_D0018.tif" />

CH₂C1

C-CH₂

OH cl

<img file="MD1255C2_D0019.tif" />

<img file="MD1255C2_D0020.tif" />

CH₂C1 c = c

<img file="MD1255C2_D0021.tif" />

H

Cl: iaZ)

<td>Example</td><td>thinner</td><td>Acid reagents</td><td>The amount П (g / mol)</td><td>Temp. (° C)</td><td>duration (Min)</td><td>ZI yield (%)</td><td>The ZTi report</td><td>Literature</td>

<td> 3</td><td>20 ml of dioxane 2mlTHF</td><td>0.2 g H₂SO₄ conc. 2.3 g of acetanhydride</td><td> 5/0,018</td><td> -2</td><td> 60</td><td> 58</td><td> 9,2</td><td></td>

<td> 4</td><td>20 ml of dioxane 2mlTHF</td><td>0.2 g H₂SO₄ conc. 2.3 g of acetanhydride</td><td> 5/0,018</td><td> 25</td><td> 30</td><td> 55</td><td> 6,5</td><td></td>

<td> 5</td><td>20 ml ethylacetate</td><td>0.2 gH₂SO₄ conc. 3 g isobutyric acid anhydride</td><td> 5/0,018</td><td> 25</td><td> 30</td><td> 50</td><td> 7,7</td><td></td>

<td>Example u comparison</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td>I</td><td>20 ml of dioxane 2mlTHF</td><td>0.2 g H₂SO₄ conc. or 2.3 g anhydride</td><td> 5/0,018</td><td> 25</td><td> 50</td><td>there is no conversion</td><td></td><td></td>

<td>П</td><td>20 m] ethylacetate 2mlTHF</td><td>0.2 g H₂SO₄ conc. 2.3 Gacetylchloride</td><td> 5/0,018</td><td> 40</td><td> 30</td><td> 23«</td><td> 6,8</td><td>Ann. chem phys. [11] 6,313 (1936)</td>

<td>Ш</td><td>50 ml formic acid</td><td></td><td> 10/0,036</td><td> 100</td><td> 50</td><td> 8,3</td><td> 3,8</td><td>J. Am. Chem. Shock. 2204 u. 2208 (1938)</td>

Continuation

<td>IV</td><td>50 gtoluenes 80 ml cyclohexane</td><td>2 gp-toluene-sulfacid</td><td> 50/0,18</td><td>dephlegmator.</td><td> 150</td><td> 46,5</td><td> 4,5</td><td>Naturwiss. 44.584 (1957)</td>

<td>V</td><td>15 gacetomtril</td><td>75 mgp-toluenesulfacid</td><td> 7,56-10³</td><td> 50</td><td> 180</td><td>there is no conversion</td><td></td><td>Tetrahedron no. 26, 4277–4286</td>

a) by analogy with the references indicated;

b) 19% of eliminated substance, 13% of acylate, formed by the OH functional group in hydrochloride IL

Example 6

Obtaining hydrochloride and in situ dehydration process l-chloro-2- (4-fluorophenyl) -3- (2-chlorophenyl) propan-2-ol

To 36.0 g (1.5 moles) of magnesium tar in 200 ml of diethyl ether 170 g (1.0 moles) of 2-chlorobenzylchloride solution in 400 ml of diethyl ether are added dropwise. Then to

-10 ° C 155 g (0.9 moles) solution of para-fluoro-co-chloracetophenone in 450 ml of diethyl ether is added dropwise and stirred at 25 ° C for another two hours.

Then, at -10 ° C, 49.0 g (0.5 mol) of sulfuric acid concentrated in 300 ml of diethyl ether were added dropwise. Warm up to 25 ° C and suck in the drop salt. The crude ethereal solution obtained is used for the reaction indicated below.

Z-3-Chloro-2- (4-fluorophenyl) -1 - (2-chlorophenyl) propene

In 525 ml of the crude solution described above, containing about 134.5 g of hydrochloride (0.45 moles), at -10 ° C add 8.0 g (0.08 moles) of concentrated sulfuric acid, after for 2 hours 57.1 g (0.56 moles) of acetanhydride were added. The fallen salt is separated by filtration. The crude alkylchloride obtained by scraping the diluent from the filtrate is used for triazole substitution or for epoxidation.

Example 7

Kinetics variant

Z-3-chloro-2- (4-fluorophenyl) -L- (2-chlorophenyl) propene

At 0 ° C by the initial mixture of 250 ml of dioxane, 25 ml of THF, 12.4 g of acetic acid (0.2 mol) and 69 g (0.23 mol) of 1-chloro-2- (4-fluorophenyl) ) -3- (2-chlorophenyl) propane-2-ol, obtained as a result of the Griniar reaction according to example 1, for about 1 hour is grown 43 g (1.02 moles) of cetane. After the ordinary processing of the product on the basis of CLVÎ, a yield is obtained, which is practically equal to the yield obtained in the case of using anhydride according to example 2. The ratio of Z-isomers and E-isomers for the given type of reaction is about 11: 1.

Examples 8 and 9

Obtaining azolylmethyloxiranes IV according to synthesis a)

Z-3- (l, 2,4-triazol-l-yl) -2- (4-chlorophenyl) -L- (2-chlorophenyl) -propen

To the solution of 11.5 g (0.17 moles) of tri azole in 150 ml of dimethylformamide is added

6.6 g of sodium hydroxide and, by mixing, they are heated to a temperature of about 70 ° C until the time of formation of a strata solution. Then it is cooled down to 10 ° C, after which for 49 hours, 49.5 g of Z-3-chloro-2- (4-chlorophenyl) -l- (2-chlorophenyl) propene are added dropwise. crude, obtained according to example 2, in 50 ml of dimethylformamide. The meal is stirred for another 4 hours at room temperature.

Add 200 ml of water and extract with multiple tertiary methyl-butyl ether. The collected organic phases are washed, dried and concentrated in vacuo. After recrystallization from tertiary methyl-butyl ether and n-hexane, 24.4 g of Z-3- (1,4-triazol-1-yl) -2- (4-chlorophenyl) -l- (2-) are obtained. chlorophenyl) propene with Ttop. from 106-110 ° C.

Cis-2- (1,4,4-triazol-1-yl-methyl) -2- (4-fluorophenyl) -3- (2-chlorophenyl) -oxirane g (0.9 moles) of maleic acid anhydride and 6 drops of concentrated sulfuric acid m 90 ml of dichloromethane together with 22 g of hydrogen peroxide with a concentration of 50% are heated to 50 ° C. 28 g (0.089 moles) of Z-3- (1,2,4-triazol-1-yl) -2- (4-fluorophenyl) -1- (2-chlorophenyl) propene in 75 ml of dichloromethane are added dropwise. The mixture 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 aspirated from the fallen maleic acid and shaken with thiosulphate solution and dilute caustic sodium solution. The dried and scraped organic phase at maximum vacuum at about 50 ° C after cooling and repeated scraping of the parent solution gives 14 g of special product (which equals 50% yield).

Examples 10 and 11

Obtaining azolylmethyloxyranes IV according to synthesis b) Cis-1-chloromethyl-2- (2-chlorophenyl) -l- (4-fluorophenyl) oxirane (compound no. 2.6 according to table 2)

Take 56.2 g (0.2 mol) of Z-3-chloro-2- (4-fluorophenyl) -l- (2-chlorophenyl) propene in 530 ml of ice-cold acetic acid and add 196 g ( 2 moles) of maleic acid anhydride. Then for 1 hour at 25 ° C add 68 g (1 mol) of hydrogen peroxide solution with 50% concentration. The mixture is stirred for a further 3-4 hours at 40 ° C, then for 10 hours at 25 ° C.

Finally, by mixing, add m 3 1 of water and 50 ml of sodium thiosulphate solution with 10% concentration and then, if necessary, again add sodium thiosulphate solution until the peroxide disappears. The colorless precipitate obtained is aspirated and dried. The crude substance obtained as a result of recrystallization from n-hexane can be used without purification (Ttop. 68-70 ° C).

Cis-2- (l, 2,4-triazol-l-yl-methyl) -2- (4-fluorophenyl) -3- (2-chlorophenyl) oxirane

1.5 g (5 mmol) of cis-1-chloromethyl-2- (2-chlorophenyl) -l- (4-fluorophenyl) oxirane and 0.69 g (7.5 mmol) of sodium 1,2,4-triazole stir for 5 hours at 75 ° C in 7 ml of DMF. After cooling the reaction mass is neutralized by the addition of an insignificant amount of acetic acid, after about 10 ml of water is added, as a result of the crystalline product falling (yield - 1.4 g). The obtained product is vacuumed, washed with water and dried in vacuo.