RU2258060C2 - Method for preparing 5-[(4-chlorophenyl)methyl]-2,2-dimethylcyclopentanone - Google Patents

Abstract

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to the improved method for preparing 5-[(4-chlorophenyl)methyl]-2,2-dimethylcyclopentanone. Method involves interaction of 1-[(4-chlorophnyl)methyl]-3-methyl-2-oxocyclopentane carboxylic acid methyl ester or 1-[(4-chlorophenyl)methyl]-3-methyl-2-oxocyclopentane carboxylic acid ethyl ester with sodium hydride and methyl halide wherein amount of sodium hydride is 1.0-1.3 mole per one mole of corresponding ester and amount methyl halide used is 1.0-1.3 mole per one mole of the parent ester followed by hydrolysis of synthesized 1-[(4-chlorophenyl)methyl]-3,3-dimethyl-2-oxocyclopentane carboxylic acid methyl ester or 1-[(4-chlorophenyl)methyl]-3,3-dimethyl-2-oxocyclopentane carboxylic acid ethyl ester. Prepared compound is used for synthesis of agricultural or garden fungicide methconazole.

EFFECT: improved preparing method.

8 cl, 5 ex

Description

FIELD OF TECHNOLOGY

The present invention relates to a method for producing 5 - [(4-chlorophenyl) methyl] -2,2-dimethylcyclopentanone, which is an important intermediate in the preparation of metconazole, which is an agricultural or horticultural fungicide.

BACKGROUND OF THE INVENTION

Japanese Patent Application Laid-Open (KOKAI) No. 1-93574 and 1-301664 disclose 5 - [(4-chlorophenyl) methyl] -2,2-dimethylcyclopentanone, and 5 - [(4-chlorophenyl) methyl] - are obtained from it 2,2-dimethyl-1- (1H-1,2,4-triazol-1-ylmethyl) cyclopentanol (metconazole), converting its carbonyl group into an epoxy group and then introducing an azolyl group into the epoxylated product. Japanese Patent Application Laid-Open (KOKAI) No. 1-93574, as a method for producing 5 - [(4-chlorophenyl) methyl] -2,2-dimethylcyclopentanone, describes the method represented by the following reaction scheme (I)

However, in the reaction scheme (I), the yield of compound (2) during the reaction of converting compound (1) to compound (2) is 81%; the yield of compound (3) during the reaction of converting compound (2) to compound (3) is 86% and therefore, the total yield of compound (3) in the reaction for converting compound (1) to compound (3) is only 70%.

In addition, Japanese Patent Application Laid-Open (KOKAI) No. 8-245517 describes a method for the interaction of 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxocycopentanecarboxylic acid methyl ester with sodium hydroxide and methyl bromide in the presence of molecular sieves with the purpose of obtaining 5 - [(4-chlorophenyl) methyl] -2,2-dimethylcyclopentanone, as represented by the following reaction scheme II):

However, in the reaction scheme (II), the yield of the compound by the reaction of converting compound (4) to compound (2) is also only 71%.

In the reaction scheme (II), where R is isopropyl, it is described that the yield is increased to 90%. However, since the resulting product (2) [R = isopropyl] has a high resistance to hydrolysis in the next step, compound (2) is not suitable as starting material for 5 - [(4-chlorophenyl) methyl] -2,2-dimethylcyclopentanone.

Further, Japanese Patent Application Laid-Open (KOKAI) No. 1-93574 further describes a process for preparing the above compound (4) from reaction scheme (II) in accordance with the following reaction scheme (III). However, a description of the yield of compound (4) is not given.

As a method for preparing compound (5), a method is also known that is represented by the following reaction scheme (IV) as described in "Precision Organic Synthesis" (published by Nanko-Do Co., Ltd.). However, any of these methods cannot achieve a high yield of the desired product.

Таким образом, способ получения 5-[(4-хлорфенил)метил]-2,2-диметилциклопентанона из диметиладипата или диэтиладипата, который легко реализуем в промышленности и обеспечивает высокий выход, не известен. Поэтому требуется разработать способ эффективного получения вышеуказанного соединения.

Thus, the method for producing 5 - [(4-chlorophenyl) methyl] -2,2-dimethylcyclopentanone from dimethyl adipate or diethyl adipate, which is easily marketable and provides a high yield, is not known. Therefore, it is required to develop a method for efficiently producing the above compound.

DESCRIPTION OF THE INVENTION

Under the above conditions, the present invention has been completed. The purpose of the present invention is to provide a simple method for producing 5 - [(4-chlorophenyl) methyl] -2,2-dimethylcyclopentanone in high yield and high quality, which is an important intermediate in the preparation of metconazole, which is an agricultural or horticultural fungicide.

As a result of earlier studies of the applicants, it was found that in carrying out specific reactions under specific conditions, methyl 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo cyclopentanecarboxylic acid or ethyl 1 - [(4-chlorophenyl) methyl ] -3-methyl-2-oxo-cyclopentanecarboxylic acid, obtained from readily available in the industry dimethyl adipate or diethyl adipate, give 5 - [(4-chlorophenyl) methyl] -2,2-dimethyl cyclopentanone of high quality and in high yield. The present invention has been achieved based on the following findings.

According to a first aspect of the present invention, there is provided a process for preparing 5 - [(4-chlorophenyl) methyl] -2,2-dimethylcyclopentanone, comprising:

reaction of 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo-cyclopentanecarboxylic acid methyl ester or 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo-cyclopentanecarboxylic acid ethyl ester with sodium hydride and methyl halide with the purpose of obtaining 1 - [(4-chlorophenyl) methyl] -3,3-dimethyl-2-oxo-cyclopentanecarboxylic acid methyl ester or 1 - [(4-chlorophenyl) methyl] -3,3-dimethyl-2-oxo-cyclopentanecarboxylic acid ethyl ester; and

hydrolysis of the obtained 1 - [(4-chlorophenyl) methyl] -3,3-dimethyl-2-oxo-cyclopentanecarboxylic acid methyl ester or 1 - [(4-chlorophenyl) methyl] -3,3-dimethyl-2-oxo-cyclopentanecarboxylic acid ethyl ester.

According to a second aspect of the present invention, there is provided a method for producing 5 - [(4-chlorophenyl) methyl] -2,2-dimethylcyclopentanone, comprising:

(1) the interaction of dimethyl adipate or diethyl adipate with a metal alkoxide;

(2) after removal of the resulting alcohol, the interaction of the obtained reaction product with methyl halide;

(3) after completion of the reaction, the interaction of the obtained reaction product with a metal alkoxide; and

(4) after removal of the resulting alcohol, the interaction of the obtained reaction product with (4-chlorophenyl) methyl chloride;

(5) reacting 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo-cyclopentanecarboxylic acid methyl ester or 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo-cyclopentanecarboxylic acid ethyl ester with sodium hydride and methyl halide; and

(6) hydrolysis of the obtained 1 - [(4-chlorophenyl) methyl] -3,3-dimethyl-2-oxo cyclopentanecarboxylic acid methyl ester or 1 - [(4-chlorophenyl) methyl] -3,3-dimethyl-2- ethyl ester oxycyclopentanecarboxylic acid.

According to a third aspect of the present invention, there is provided a process for the preparation of 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo-cyclopentanecarboxylic acid methyl ester or 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo-cyclopentanecarboxylate acid, including:

(1) the interaction of dimethyl adipate or diethyl adipate with a metal alkoxide;

(2) after removal of the resulting alcohol, the interaction of the obtained reaction product with methyl halide;

(3) after completion of the reaction, the interaction of the obtained reaction product with a metal alkoxide; and

(4) after removal of the resulting alcohol, the interaction of the obtained reaction product with (4-chlorophenyl) methyl chloride.

According to a fourth aspect of the present invention, there is provided a method for using 5 - [(4-chlorophenyl) methyl] -2,2-dimethylcyclopentanone as an intermediate to produce methconazole or to produce agricultural or horticultural fungicides.

According to a fifth aspect of the present invention, there is provided a method for using 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo-cyclopentanecarboxylic acid methyl ester or 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo-cyclopentanecarbonyl ester acid as an intermediate for the preparation of 5 - [(4-chlorophenyl) methyl] -2,2-dimethylcyclopentanone, for the preparation of metconazole or for the production of agricultural or horticultural fungicides.

According to a sixth aspect of the present invention, there is provided a method for using 1 - [(4-chlorophenyl) methyl] -3,3-dimethyl-2-oxo cyclopentanecarboxylic acid methyl ester or 1 - [(4-chlorophenyl) methyl] -3,3-dimethyl ethyl ester -2-oxo-cyclopentanecarboxylic acid as an intermediate for the preparation of metconazole or for the production of agricultural or horticultural fungicides.

In more detail, the present invention will be described below.

In the following description, 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo-cyclopentanecarboxylic acid methyl ester and 1 - [(4-chlorophenyl) methyl] -3,3-dimethyl-2-oxo-cyclopentanecarboxylic acid methyl ester are chemically identical to 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo-cyclopentanecarboxylic acid ethyl ester and 1 - [(4-chlorophenyl) methyl] -3,3-dimethyl-2-oxo-cyclopentanecarboxylic acid ethyl ester. Therefore, clarifications are made only regarding the above methyl esters.

A method for the preparation of 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo-cyclopentanecarboxylic acid methyl ester will be described below.

The method for producing 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo-cyclopentanecarboxylic acid methyl ester comprises the following four steps.

The first stage (condensation reaction with ring closure):

Methyl adipate is reacted with metal methoxide. The resulting reaction product is subjected to demethanolization (removal of methanol), to obtain the sodium salt of 2-oxocyclopentanecarboxylic acid methyl ester.

The second stage (first methylation reaction):

The resulting sodium salt of 2-oxo-cyclopentanecarboxylic acid methyl ester is reacted with methyl halide to obtain 1-methyl-2-oxo-cyclopentanecarboxylic acid methyl ester.

Third stage (ring opening / condensation reaction with ring closure):

The resulting 1-methyl-2-oxo-cyclopentanecarboxylic acid methyl ester is reacted with metal methoxide to subject the methyl ester to ring opening and ring-closure condensation reactions, thereby obtaining the 3-methyl-2-oxo-cyclopentanecarboxylic acid methyl ester sodium salt.

The fourth stage (reaction (4-chlorophenyl) methylation):

The obtained 3-methyl-2-oxo-cyclopentanecarboxylic acid methyl ester sodium salt is reacted with (4-chlorophenyl) methyl chloride to obtain 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxocycopentanecarboxylic acid methyl ester.

The above steps one through four will be described in more detail below.

Specifically, methyl 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo-cyclopentanecarboxylic acid methyl ester can be obtained in high yield by continuously performing the above steps one through four without isolation or purification during these steps under the following operating conditions ( loaded amounts, reaction conditions, etc.).

First stage:

Since the sodium salt of 2-oxo cyclopentanecarboxylic acid methyl ester is a solid as a reaction product of the first step, the first step is carried out in a solvent. As suitable solvents in the first stage, aprotic solvents having a boiling point of usually not lower than 75 ° C can be used, since methanol must be distilled off from the reaction solution. Examples of solvents may include aromatic compounds such as benzene, toluene, xylene and chlorobenzene; ester-based compounds such as dimethoxyethane and dioxane or the like. Among these solvents, toluene, xylene and chlorobenzene are preferred.

Then, dimethyl adipate and metal methoxide are charged into the solvent. The resulting mixture was heated under normal pressure or under reduced pressure to distill off the methanol with the solvent. The reaction temperature is usually from 70 to 150 ° C., Preferably from 80 to 130 ° C. If required, an additional amount of solvent may be added to the reaction system.

Examples of metal methoxides include sodium methoxide, potassium methoxide, or similar compounds. Among these metal methoxides, sodium methoxide is preferred. Metal methoxides can be used in the form of either a powder or a methanol solution. The amount of metal methoxide used is usually from 0.9 to 1.0 moles per mole of charged dimethyl adipate. When the amount of metal methoxide used is less than 0.9 mol, the conversion of dimethyl adipate can be significantly reduced. When the amount of metal methoxide used exceeds 1.0 mol, removal of methanol from the reaction system can be difficult, resulting in a significant decrease in yield.

During the course of the reaction, the sodium salt of 2-oxocyclopentanecarboxylic acid methyl ester precipitates as the reaction product of the first stage. In order to reduce the viscosity of the resulting suspension and facilitate its mixing, it may be effective to add a small amount of an aprotic polar solvent. As aprotic polar solvents, dimethyl sulfoxide (DMSO), N-methylpyrrolidone, dimethylimidazoline, dimethylacetamide, dimethylformamide or the like can be mentioned.

In the first reaction step, it is important to sufficiently remove the methanol present in the reaction system. If even a very small amount of methanol remains in the reaction system, the yield is significantly impaired.

Second stage:

Then, the sodium salt of 2-oxo cyclopentanecarboxylic acid methyl ester obtained in the first step is reacted with methyl halide. The reaction temperature of the second stage is usually from 50 to 120 ° C, preferably from 70 to 100 ° C.

As the methyl halides, methyl chloride, methyl bromide or methyl iodide can be mentioned. The amount of methyl halide used is usually from 0.9 to 1.1 mol per 1 mol of dimethyl adipate loaded in the first stage. When the amount of methyl halide is less than 0.9 mol, the reaction may not complete. When the amount of methyl halide is more than 1.1 moles, although no adverse effect is exerted, additional beneficial effects cannot be expected.

After completion of the reaction, excess methyl halide still present in the reaction system, if any, is removed by distillation. If the reaction solution, still containing residual methyl halide, is subjected to the next step, a significant amount of the metal methoxide added in the next step is consumed, thereby adversely affecting the reaction.

Further, 1-methyl-2-oxo-cyclopentanecarboxylic acid methyl ester as a reaction product of the second stage has a relatively low boiling point and high solubility in water. Therefore, when the reaction product is washed with water or the solvent is distilled off at this stage, the yield is significantly impaired.

Third stage:

Then, metal methoxide is added to the reaction product obtained in the second stage. The resulting mixture was heated under normal pressure or under reduced pressure to distill off the methanol together with the solvent in the same manner as used in the first stage. The reaction temperature is usually from 70 to 150 ° C., Preferably from 80 to 130 ° C. If required, an additional amount of solvent can be added to the reaction mixture.

As the metal methoxide used in the third step, it is preferable to use the same metal methoxide as used in the first step. The amount of metal methoxide loaded at this stage is usually from 0.9 to 1.0 mol per 1 mol of dimethyl adipate loaded in the first stage. When the amount of loaded metal methoxide is less than 0.9 mol, the conversion percentage of dimethyl adipate can be significantly reduced. When the amount of loaded metal methoxide exceeds 1.0 mol, the removal of methanol in the reaction system may become difficult, which leads to a noticeable deterioration in yield.

When a reaction occurs, the sodium salt of 3-methyl-2-oxo-cyclopentanecarboxylic acid methyl ester precipitates as a third-stage reaction product. In order to lower the viscosity of the resulting suspension and facilitate its mixing, it may be effective to add a small amount of an aprotic polar solvent. As aprotic polar solvents, dimethyl sulfoxide (DMSO), N-methylpyrrolidone, dimethylimidazoline, dimethylacetamide, dimethylformamide or the like can be mentioned.

In the third stage of the reaction, it is important to sufficiently remove the methanol present in the reaction system. If even a very small amount of methanol still remains in the reaction system, the yield of the desired product is significantly reduced.

Fourth stage:

The 3-methyl-2-oxo-cyclopentanecarboxylic acid methyl ester sodium salt obtained in the third step is then reacted with (4-chlorophenyl) methyl chloride. The reaction temperature of the second stage is usually from 60 to 150 ° C., Preferably from 80 to 130 ° C. The amount of (4-chlorophenyl) methyl chloride used is usually from 0.9 to 1.0 mol per 1 mol of dimethyl adipate loaded in the first step. When the amount of (4-chlorophenyl) methyl chloride is less than 0.9 mol, the 3-methyl-2-oxo-cyclopentanecarboxylic acid methyl ester sodium salt obtained in the third step may remain unused, resulting in a decrease in the yield of the desired product. When the amount of (4-chlorophenyl) methyl chloride used exceeds 1.0 mol, the excess of added (4-chlorophenyl) methyl chloride after the completion of the reaction may remain unused, resulting in undesirable side reactions in the subsequent step.

When the starting reagents were completely consumed, the reaction was stopped to rinse the reaction product with water and distill off the solvent, thereby isolating high-quality 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo cyclopentanecarboxylic acid methyl ester. The 1 - [(4-chlorophenyl) methyl] -3-methyl-2-hydroxycyclopentanecarboxylic acid methyl ester thus obtained has a high boiling point and low solubility in water. Therefore, losses that occur after the above treatments can be ignored.

A method for producing 5 - [(4-chlorophenyl) methyl] -2,2-dimethylcyclopentanone will be described below.

The method for producing 5 - [(4-chlorophenyl) methyl] -2,2-dimethylcyclopentanone from methyl ester of 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxocyclopentanecarboxylic acid involves the following two steps.

Fifth stage (second methylation reaction):

Then, 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo-cyclopentanecarboxylic acid methyl ester is reacted with sodium hydride and methyl halide to produce 1 - [(4-chlorophenyl) methyl] -3,3-dimethyl methyl ester -2-oxo cyclopentanecarboxylic acid.

Sixth stage (hydrolysis):

The 1 - [(4-chlorophenyl) methyl] -3,3-dimethyl-2-oxo-cyclopentanecarboxylic acid methyl ester thus obtained is hydrolyzed to give 5 - [(4-chlorophenyl) methyl] -2,2-dimethylcyclopentanone.

The above fifth to sixth steps will be described in more detail below.

More specifically, a process for the preparation of 5 - [(4-chlorophenyl) methyl] -2,2-dimethylcyclopentanone in high yield can be carried out by treating 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo cyclopentanecarboxylic acid methyl ester with the following working conditions (loaded amount, reaction conditions, etc.).

Fifth stage:

Then, 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo-cyclopentanecarboxylic acid methyl ester is reacted with sodium hydride and methyl halide in a solvent at a temperature usually from 60 to 120 ° C, preferably from 80 to 100 ° C. When the reaction temperature is less than 60 ° C, the reaction rate is too low and becomes impractical. When the reaction temperature is above 120 ° C, undesirable side reactions, such as O-alkylation, can often occur.

As solvents, any aprotic solvents may be used provided that the solvents do not react with sodium hydride or an alkyl halide. Examples of solvents may include aromatic compounds such as benzene, toluene, xylene and chlorobenzene; ether-based compounds such as tetrahydrofuran (THF), dimethoxyethane and dioxane; aprotic polar compounds such as dimethylformamide, dimethylacetamide, N-methylpyrrolidone and dimethyl sulfoxide or the like. These solvents can be used individually or in the form of a mixture of two or more of any solvents. In particular, it is preferable to use a mixed solvent consisting of an aromatic compound and an ether-based compound or an aprotic polar compound.

The amount of sodium hydride used in the fifth step is usually from 1.0 to 1.3 mol, preferably from 1.1 to 1.2 mol, per 1 mol of methyl ester 1 - [(4-chlorophenyl) methyl] -3-methyl-2 -oxycyclopentanecarboxylic acid. When the amount of sodium hydride used is less than 1.0 mol, the reaction may not complete completely, resulting in a low yield of the desired product. When the amount of sodium hydride used exceeds 1.3 moles, complex subsequent treatments may be required after completion of the reaction.

As the methyl halides, methyl chloride, methyl bromide or methyl iodide can be mentioned. Among these methyl halides, methyl bromide and methyl iodide are preferred. If methyl bromide is used, catalytic amounts of sodium iodide or potassium iodide can be added to it. The amount of methyl halide used is usually from 1.0 to 1.3 mol, preferably from 1.0 to 1.2 mol, per 1 mol of 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo cyclopentanecarboxylic acid methyl ester. When the amount of methyl halide used is less than 1.0 mole, the reaction may not be complete, resulting in a low yield of the desired product. When the amount of methyl halide used exceeds 1.3 moles, part of the methyl halide may be destroyed.

The reaction of this fifth step is a highly exothermic reaction and generates hydrogen. Therefore, it is preferable that after adding sodium hydride to the solvent, 1 - [(4-chlorophenyl) methyl] -3-methyl-2-hydroxycyclopentanecarboxylic acid methyl ester and methyl halide are added to the solvent, and they react with each other while maintaining the temperature solvent at the above reaction temperature. After the methyl ester of 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxycyclopentanecarboxylic acid was consumed as a starting material in the reaction system, the resulting reaction mixture was poured into water, washed with water and then subjected to distillation under nitrogen atmosphere to remove the solvent therefrom, thereby isolating 1 - [(4-chlorophenyl) methyl] -3,3-dimethyl-2-oxocylopentanecarboxylic acid methyl ester.

Sixth stage:

The hydrolysis and decarboxylation reaction of 1 - [(4-chlorophenyl) methyl] -3,3-dimethyl-2-oxo cyclopentanecarboxylic acid methyl ester is carried out at a temperature usually from 50 ° C to the temperature of phlegm formation in an acidic or alkaline medium.

In the case where the hydrolysis and decarboxylation reaction is carried out in an acidic medium, acetic acid can be used as a solvent in addition to water. In addition, catalysts can be added to this system. Inorganic acids such as hydrochloric acid, hydrobromic acid and sulfuric acid can be used as catalysts. The temperature of the hydrolysis and decarboxylation reaction is usually from 50 ° C to reflux temperature, preferably from 80 ° C to reflux temperature.

In the case where the hydrolysis and decarboxylation reaction is carried out in an alkaline medium, lower alcohols or aromatic hydrocarbons can be used as a solvent in combination with water. Alkali metal hydroxides, preferably sodium hydroxide or potassium hydroxide, can be used as alkali. The temperature of the hydrolysis and decarboxylation reactions in an alkaline medium is usually from 50 ° C. to the reflux temperature, preferably from 80 ° C. to the reflux temperature.

After the methyl ester of 1 - [(4-chlorophenyl) methyl] -3,3-dimethyl-2-oxocyclopentanecarboxylic acid was consumed as a starting material in the reaction system, the resulting reaction mixture was extracted with a solvent, washed with water and then distilled to remove solvent therefrom, thereby isolating 5 - [(4-chlorophenyl) methyl] -2,2-dimethylcyclopentanone. After that, if necessary, the reaction product is purified by distillation or similar methods.

BEST MODE FOR CARRYING OUT THE INVENTION

The present invention is described in more detail by examples, but the following examples are only illustrative and, therefore, it is assumed that they do not limit the scope of the present invention.

Example 1

One liter of toluene, 174.2 g of dimethyl adipate, 189.1 g of 28% sodium methylate and 15 g of dimethylformamide (DMF) were charged into a 2 liter four-necked flask and heated under normal pressure with stirring under a nitrogen atmosphere to distill methanol / toluene. During heating, 0.5 liter of toluene is suitably added to the flask. After the methanol was completely distilled off, the resulting reaction mixture was cooled to 80 ° C and 100 g of methyl bromide was added dropwise to the reaction mixture, while its temperature was maintained at 80 ° C.

After rushing, the reaction mixture was stirred at 80 ° C for 2 hours, and then the excess methyl bromide was distilled off under reduced pressure.

To the resulting reaction solution were added 187.2 g of 28% sodium methylate and 15 g of dimethylformamide (DMF). The resulting mixture was heated under normal pressure in a nitrogen atmosphere with stirring to distill the methanol / toluene mixture out of it. During heating, toluene and DMF are appropriately added to the flask in total quantities of 0.5 liters and 15 g, respectively. After the methanol was completely distilled off, the resulting reaction mixture was cooled to 100 ° C and then 153 g of (4-chlorophenyl) methyl chloride was added dropwise to the reaction mixture, while the temperature of the mixture was maintained at 100 ° C.

After being added dropwise, the resulting reaction mixture was refluxed for 3 hours. After completion of the reaction, the separated organic phase is washed with water and distilled to remove the solvent, thereby obtaining 277.7 g of a light yellow oily substance. The purity of the obtained product is determined by gas chromatography. As a result, it was confirmed that the purity of the obtained 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo cyclopentanecarboxylic acid methyl ester was 93%, and its yield was 92% with respect to the loaded methyladipate.

Example 2

44.1 g of 60% sodium hydride are charged into a 1-liter four-necked flask and the paraffins are removed from it by decantation using toluene. Then, 100 ml of toluene, 20 ml of dimethoxyethane and 1 g of sodium iodide are added to the flask. The flask as a reactor is equipped with a refrigerator filled with dry ice, and immersed in a bath, the temperature of which is maintained at 80 ° C. 277.7 g of 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxocylopentanecarboxylic acid methyl ester obtained in Example 1 and 100 g of methyl bromide are slowly added dropwise to the flask, so that a strong exothermic reaction is generated to generate hydrogen. 2 hours after the dropwise addition, the methyl 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxocyclopentanecarboxylic acid methyl ester is completely consumed in the reaction system.

The resulting reaction mixture was poured into water under a nitrogen atmosphere, and the organic phase was separated from the reaction mixture, washed with water and then distilled to remove solvent from it, thereby obtaining 280 g of a light yellow oily substance. The analysis of the oily substance by gas chromatography confirms that the purity of the 1 - [(4-chlorophenyl) methyl] -3,3-dimethyl-2-oxocyclopentanecarboxylic acid methyl ester thus obtained is 92%, and its yield is 95% relative to the methyl ester 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxocyclopentanecarboxylic acid.

Example 3

600 ml of acetic acid, 30 ml of water, 70 g of sulfuric acid and 280 g of 1 - [(4-chlorophenyl) methyl] -3,3-dimethyl-2-hydroxycyclopentanecarboxylic acid methyl ester obtained in Example 2 are charged into a 1 liter four-necked flask. and stirred at 107 ° C for 8 hours. After completion of the reaction, toluene and water are added to the reaction solution, and then the organic phase is separated from the solution, washed with water and then subjected to distillation to remove the solvent from it, thereby obtaining a light yellow oily substance. The obtained oily substance is subjected to simple distillation under a pressure of from 1 to 2 mm Hg, whereby 210.2 g of distillate having a distillation temperature of from 120 to 130 ° C. are obtained. The analysis of the distillate by gas chromatography confirms that the purity of the thus obtained 5 - [(4-chlorophenyl) methyl] -2,2-dimethylcyclopentanone is 95.5% and its yield is 97% relative to 1 - [(4- chlorophenyl) methyl] -3,3-dimethyl-2-oxo-cyclopentanecarboxylic acid.

Example 4

500 ml of a 25% aqueous solution of sodium hydroxide and 280 g of 1 - [(4-chlorophenyl) methyl] -3,3-dimethyl-2-oxo cyclopentanecarboxylic acid methyl ester obtained in Example 2 are charged into a 1 liter four-necked flask and refluxed within 4 hours. After completion of the reaction, toluene and water are added to the reaction solution, and then the organic phase is separated from the solution, washed with water and then subjected to distillation to remove the solvent from it, thereby obtaining a light yellow oily substance. The obtained oily substance is subjected to simple distillation under pressure from 1 to 2 mm Hg, thereby obtaining 201.6 g of distillate having a distillation temperature of from 120 to 130 ° C. The analysis of the distillate by gas chromatography confirms that the purity of the thus obtained 5 - [(4-chlorophenyl) methyl] -2,2-dimethylcyclopentanone is 97.5% and its yield is 95% relative to 1 - [(4- chlorophenyl) methyl] -3,3-dimethyl-2-oxo-cyclopentanecarboxylic acid.

Example 5:

The same procedure is carried out as defined in Example 1, except that instead of 28% sodium methylate, sodium methylate powder is used in the same molar amount as in Example 1. As a result, it is confirmed that the same results are obtained as in Example 1 .

APPLICABILITY IN INDUSTRY

According to the method of the present invention, with high quality and high yield, 5 - [(4-chlorophenyl) methyl] -2,2-dimethylcyclopentanone can be obtained as an important intermediate for the production of agricultural or horticultural fungicides.

Claims (8)

1. The method of obtaining 5 - [(4-chlorophenyl) methyl] -2,2-dimethylcyclopentanone, including the interaction of methyl ester of 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo-cyclopentanecarboxylic acid or ethyl ester of 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo-cyclopentanecarboxylic acid with sodium hydride and methyl halide, moreover, the amount of sodium hydride used in this reaction is from 1.0 to 1.3 mol per mole of 1 - [((4-chlorophenyl) methyl] -3-methyl-2-oxo cyclopentanecarboxylic acid methyl or ethyl ester, and the amount of methyl halide used from 1.0 to 1.3 mol per mol of methyl or ethyl ether 1 - [(4-chlorof nile) methyl] -3-methyl-2-oxocyclopentanecarboxylic acid methyl ester; and hydrolysis of the obtained 1 - [(4-chlorophenyl) methyl] -3,3-dimethyl-2-oxo-cyclopentanecarboxylic acid methyl ester or 1 - [(4-chlorophenyl) methyl] -3,3-dimethyl-2-oxo-cyclopentanecarboxylic acid ethyl ester. 2. The method according to claim 1, where the methyl ester of 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxocyclopentanecarboxylic acid or the ethyl ester 1 - [(4-chlorophenyl) methyl] -3-methyl-2 -oxycyclopentanecarboxylic acid receive (1) the interaction of dimethyl adipate or diethyl adipate with a metal alkoxide, wherein the amount of metal alkoxide used is from 0.9 to 1.0 mol per mole of charged dimethyl adipate or diethyl adipate; (2) after removal of the resulting alcohol by reaction of the obtained reaction product with methyl halide, the amount of methyl halide used being from 0.9 to 1.1 mol per mole of dimethyl adipate or diethyl adipate loaded in step (1); (3) after completion of the reaction by reaction of the obtained reaction product with a metal alkoxide, wherein the amount of charged metal alkoxide is from 0.9 to 1.0 mol per mole of dimethyl adipate or diethyl adipate loaded in step (1); and (4) after removal of the resulting alcohol by reaction of the obtained reaction product with (4-chlorophenyl) methyl chloride, the amount of (4-chlorophenyl) methyl chloride used being from 0.9 to 1.0 mol per mole of dimethyl adipate loaded in step (1) or diethyl adipate. 3. The method of obtaining methyl ester of 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo-cyclopentanecarboxylic acid or ethyl ester of 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo-cyclopentanecarboxylic (1) the interaction of dimethyl adipate or diethyl adipate with a metal alkoxide, wherein the amount of metal alkoxide used is from 0.9 to 1.0 mol per mole of charged dimethyl adipate or diethyl adipate; (2) after removal of the resulting alcohol, the interaction of the obtained reaction product with methyl halide, wherein the amount of methyl halide used is from 0.9 to 1.1 mol per mole of dimethyl adipate loaded in step (1); (3) after completion of the reaction, the reaction product obtained is reacted with a metal alkoxide, wherein the amount of charged metal alkoxide is from 0.9 to 1.0 mol per mole of dimethyl adipate or diethyl adipate loaded in step (1); and (4) after removal of the resulting alcohol, the reaction product obtained is reacted with (4-chlorophenyl) methyl chloride, the amount of (4-chlorophenyl) methyl chloride used being from 0.9 to 1.0 mol per mole of dimethyl adipate loaded in step (I) or diethyl adipate. 4. Method for the preparation of 1 - [(4-chlorophenyl) methyl] -3,3-dimethyl-2-oxo cyclopentanecarboxylic acid methyl ester or 1 - [(4-chlorophenyl) methyl] -3,3-dimethyl-2- ethyl ester oxycyclopentanecarboxylic acid, including the interaction of methyl ester of 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo-cyclopentanecarboxylic acid or ethyl ester of 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo-cyclopentanecarboxylic acid with sodium hydride and methyl halide, moreover, the amount of sodium hydride used in this reaction is from 1.0 to 1.3 mol per mole of 1 - [((4-chlorophenyl) methyl] -3-methyl-2-oxo cyclopentanecarboxylic acid methyl or ethyl ester, and the amount of methyl halide used from 1.0 to 1.3 mol per mol of methyl or ethyl ether 1 - [(4-chlorof nile) methyl] -3-methyl-2-oxocyclopentanecarboxylic acid. 5. The method of obtaining 5 - [(4-chlorophenyl) methyl] -2,2-dimethyl-1- (1H-1,2,4-triazol-1-ylmethyl) cyclopentanol (Metconazole), including reaction of 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo-cyclopentanecarboxylic acid methyl ester or 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo-cyclopentanecarboxylic acid ethyl ester with sodium hydride and methyl halide; hydrolysis of the obtained 1 - [(4-chlorophenyl) methyl] -3,3-dimethyl-2-oxo cyclopentanecarboxylic acid methyl ester or 1 - [(4-chlorophenyl) methyl] -3,3-dimethyl-2-oxo cyclopentanecarboxylic acid ethyl ester to give 5 - [(4-chlorophenyl) methyl] -2,2-dimethylcyclopentanone and subsequent conversion of 5 - [(4-chlorophenyl) methyl] -2,2-dimethylcyclopentanone to 5 - [(4-chlorophenyl) methyl] -2,2-dimethyl-1- (1H-1,2,4-triazole-1 -ylmethyl) cyclopentanol, moreover, the amount of sodium hydride used in this reaction is from 1.0 to 1.3 mol per mole of 1 - [((4-chlorophenyl) methyl] -3-methyl-2-oxo cyclopentanecarboxylic acid methyl or ethyl ester, and the amount of methyl halide used from 1.0 to 1.3 mol per mole of methyl 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo cyclopentanecarboxylic acid methyl or ethyl ester. 6. The method of obtaining 5 - [(4-chlorophenyl) methyl] -2,2-dimethyl-1- (1H-1,2,4-triazol-1-ylmethyl) cyclopentanol (metconazole) according to claim 5, where methyl ether 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo-cyclopentanecarboxylic acid or ethyl ester 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo-cyclopentanecarboxylic acid (1) the interaction of dimethyl adipate or diethyl adipate with a metal alkoxide, wherein the amount of metal alkoxide used is from 0.9 to 1.0 mol per mole of charged dimethyl adipate or diethyl adipate; (2) after removal of the resulting alcohol by reaction of the obtained reaction product with methyl halide, the amount of methyl halide used being from 0.9 to 1.1 mol per mole of dimethyl adipate or diethyl adipate loaded in step (1); (3) after completion of the reaction by reaction of the obtained reaction product with a metal alkoxide, wherein the amount of charged metal alkoxide is from 0.9 to 1.0 mol per mole of dimethyl adipate or diethyl adipate loaded in step (1); and (4) after removal of the resulting alcohol by reaction of the obtained reaction product with (4-chlorophenyl) methyl chloride, the amount of (4-chlorophenyl) methyl chloride used being from 0.9 to 1.0 mol per mole of dimethyl adipate loaded in step (1) or diethyl adipate. 7. A method of producing agricultural or horticultural fungicide Metconazole, including reaction of 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo-cyclopentanecarboxylic acid methyl ester or 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo-cyclopentanecarboxylic acid ethyl ester with sodium hydride and methyl halide; hydrolysis of the obtained 1 - [(4-chlorophenyl) methyl] -3,3-dimethyl-2-oxo-cyclopentanecarboxylic acid methyl ester or 1 - [(4-chlorophenyl) methyl] -3,3-dimethyl-2-oxo-cyclopentanecarboxylic acid ethyl ester with obtaining 5 - [(4-chlorophenyl) methyl] -2,2-dimethylcyclopentanone and subsequent conversion of 5 - [(4-chlorophenyl) methyl] -2,2-dimethylcyclopentanone to 5 - [(4-chlorophenyl) methyl] -2,2-dimethyl-1- (1H-1,2,4-triazole-1 -ylmethyl) cyclopentanol, moreover, the amount of sodium hydride used in this reaction is from 1.0 to 1.3 mol per mole of 1 - [((4-chlorophenyl) methyl] -3-methyl-2-oxo cyclopentanecarboxylic acid methyl or ethyl ester, and the amount of methyl halide used from 1.0 to 1.3 mol per mole of methyl 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo cyclopentanecarboxylic acid methyl or ethyl ester. 8. The method of producing agricultural or horticultural fungicide Metconazole according to claim 7, where 1 - [(4-chlorophenyl) methyl] -3-methyl-2-oxo-cyclopentanecarboxylic acid methyl ester or 1 - [(4-chlorophenyl) methyl] ethyl ester 3-methyl-2-oxocyclo-pentanecarboxylic acid get (1) the interaction of dimethyl adipate or diethyl adipate with a metal alkoxide, wherein the amount of metal alkoxide used is from 0.9 to 1.0 mol per mole of charged dimethyl adipate or diethyl adipate; (2) after removal of the resulting alcohol by reaction of the obtained reaction product with methyl halide, the amount of methyl halide used being from 0.9 to 1.1 mol per mole of dimethyl adipate or diethyl adipate loaded in step (1); (3) after completion of the reaction by reaction of the obtained reaction product with a metal alkoxide, wherein the amount of charged metal alkoxide is from 0.9 to 1.0 mol per mole of dimethyl adipate or diethyl adipate loaded in step (1), and (4) after removal of the resulting alcohol by reaction of the obtained reaction product with (4-chlorophenyl) methyl chloride, the amount of (4-chlorophenyl) methyl chloride used being from 0.9 to 1.0 mol per mole of dimethyl adipate loaded in step (1) or diethyl adipate.