JPS6145612B2 - - Google Patents

Description

[Detailed description of the invention]

This invention relates to a method for producing methyl and ethyl esters of cyclopropanecarboxylic acid. Substituted cyclopropane carboxylic acids are esters of the above-mentioned carboxylic acids having agrochemical activity, especially 3
-Phenoxybenzyl and alpha-cyano-
It is useful as an intermediate in producing 3-phenoxybenzyl ester. This compound with pesticide activity, so-called "synthetic pyrethroid",
It has particularly excellent insecticidal properties, and on the other hand, has very low toxicity to mammals. The combination of these two properties has made this compound of considerable interest to the agrochemical industry and has led to economic routes to "synthetic pyrethroids", particularly for the production of substituted cyclopropane carboxylic acids. Although much effort has been made to determine synthetic routes, no established synthetic routes for substituted cyclopropane carboxylic acids are found in the prior literature. The applicant, who had been studying the economical route to cyclopropanoic acid, finally succeeded in synthesizing a substituted cyclopropane nitrile, but at that time it was not yet possible to convert this nitrile into the corresponding acid or ester. I couldn't convert it. The applicant has attempted alcoholysis in the presence of acid catalysts, following many recommendations in standard textbooks, but has found that the yields of the corresponding alkyl esters are very low, and often This resulted in the formation of large amounts of lactones and other by-products. It is well known that nitriles are converted to esters by the Pinner reaction (“Houben-Weyl
Handbuch der Organischen Chemie”H.
Heneka.Book 8536-539 (1952) and “Chemical Reviews” Robert Roger and
(See Douglas Neilson, pp. 181-184 (1961)). In that process, the nitrile is treated with an alkanol and hydrogen bromide or hydrogen chloride in anhydrous conditions at or below ambient temperature to hydrolyze the resulting water-sensitive iminoether. However, in the case of cyclopropanenitrile, the pinner reaction conditions had no effect even after 24 hours. Surprisingly, the applicant has now discovered that by modifying the pinner conditions, substituted cyclopropanenitrile can be easily converted to its methyl or ethyl ester. Accordingly, the present invention provides a method for producing compounds having the following general formula. (In the general formula, R ₁ and R ₂ are each independently 1 to
is an alkyl group with 4 carbon atoms, or R ₁ and R ₂ together are an alkylene group with _up to ₅ carbon atoms;
are each independently a hydrogen atom, an alkyl group with 1 to 4 carbon atoms, a halogen atom, or X ₁ and X ₂ together are an alkylene group with up to 5 carbon atoms. Yes, or
X ₁ is a hydrogen atom, X ₂ is a monohalobinyl group, dihalobinyl group or dimethylvinyl group, and R is a methyl or ethyl group). In that method, cyclopropanenitrile with the general formula: Reacted with methanol or ethanol in essentially anhydrous conditions at a temperature within the range of 80° to 200°C in the presence of sulfuric acid as a reaction catalyst and as a scavenger for the ammonia formed during the reaction. be. The reaction temperature is preferably maintained within the range of 100° to 200°C, and more preferably within the range of 140° to 200°C. In the case of the reaction mixture used in the process according to the invention, a pressure above atmospheric pressure,
For example, pressures in the range 1 to 10 atmospheres are often used. Generally, pressures in the range of 1 to 5 atmospheres have been found to be sufficient. Using sulfuric acid, the required esters are obtained in good yields. It has been found necessary to carry out the reaction in substantially anhydrous conditions. Substantially anhydrous means that the amount of water present during the reaction is kept to a minimum, e.g., less than about 5%, preferably less than 1%, and preferably less than 0.5% by weight of the reaction mixture. That's true. For example, the moisture in concentrated sulfuric acid that is normally introduced when concentrating the acid used in this process does not significantly affect the reaction as long as both the alcohol and nitrile reactants are substantially dry. As the reaction progresses, ammonia is evolved, which neutralizes the acid catalyst, so that a sufficient amount of acid must be present to provide the necessary catalytic action. As a general condition, the weight ratio of acid to nitrile present in the process according to the invention should be in the range from 3:1 to 1:1. The applicant believes that in the alcoholysis reaction,
Only ethanol and methanol are capable of giving the esters corresponding to the nitriles of the general formula () in satisfactory yields and with little formation of undesired by-products under the conditions defined above. I discovered that it can be done. Ethanol is a desirable reagent because of the relatively short reaction times in ethanolysis according to this discovery, and also because of the economic attractiveness of using such a readily available chemical. In the compound of general formula (), desirably,
R ₁ and R ₂ are methyl groups, X ₁ and X ₂ are chlorine or bromine atoms, or methyl groups, or X ₁ is a hydrogen atom and X ₂ is a dichlorovinyl group, dibromovinyl group, difluorovinyl group, It is a chlorofluorovinyl group or a dimethylvinyl group, and R is methyl or ethyl. As mentioned earlier, by an alcoholysis reaction, cyclopropane nitrile is converted to the corresponding methyl or ethyl ester, which is then converted into 3-phenoxybenzyl alcohol or alpha-cyano-3-phenyl ester. It can be converted to the "synthetic pyrethroid" via the free acid or acid chloride by reaction with enoxybenzyl alcohol. The following nitriles are the most important pyrethroid intermediates with the greatest pesticide activity. 2,2,3,3-tetramethylcyclopropanenitrile, 3,3-dimethyl-2-(2,2-dimethylvinyl)cyclopropanenitrile, 3,3-dimethyl-2-(2,2-dichlorovinyl) Cyclopropanenitrile, and 3,3-dimethyl-2-(2,2-dibromovinyl)cyclopropanenitrile. Since in the process according to the invention the starting nitrile and the final product ester have asymmetric carbon atoms, the ester and the nitrile can exist in a corresponding number of stereoisomeric forms. The process according to the invention therefore also comprises the preparation of compounds of general formula () existing in the form of single stereoisomers or mixtures thereof. The invention will be further illustrated by the following examples. Example Preparation of methyl 3,3-dimethyl-2-(2,2-dichlorovinyl)cyclopropanecarboxylate 2.0 g (0.11 mol) of essentially dry 3.3
A mixture of -dimethyl-2-(2,2-dichlorovinyl)cyclopropanenitrile and 12 ml of a sulfuric acid/methanol solution (containing 20% by weight of concentrated sulfuric acid in dry methanol) was heated to 100% by weight in an autoclave.
The reaction was carried out at ℃ (5 atm) for 32 hours. Then water was added and the product was extracted with methylene chloride.
The organic phase was washed with dilute sodium bicarbonate and dried over magnesium sulfate to give methyl 3,3-dimethyl-2-(2,2-dichlorovinyl)cyclopropane carboxylate (95% conversion, methyl 100% selectivity for esters). Example ~ Preparation of ethyl 3,3-dimethyl-2-(2,2-dichlorovinyl)cyclopropanecarboxylate The method of Example was repeated, except that methanol was used as the alcoholysis reagent instead of methanol. ethanol and various concentrations of nitrile were used. The reaction conditions and experimental results are shown in Table A.

[Table] Examples of Comparative Experiments A number of comparative experiments were conducted, in which methanol, ethanol, isopropanol, and n-butanol were used as alcoholysis reagents, and three types of acid catalysts were used. The same nitrile (DCVN) used in the previous example was used. The reaction conditions and experimental results are shown in Table B. According to the table, the yield of DCVA-ester is considerably lower than the yield of ester made by the process according to the invention and is necessarily accompanied by undesired by-products, especially the corresponding amides and lactones.

[Table] The reason why lactone is produced as a by-product is probably that lactone is produced by acid-catalyzed ring opening followed by alcoholysis and ring closure. Furthermore, in the case of ethanolysis, the reaction time is much longer than in the examples.

Claims (1)

[Claims] 1. A method for producing a compound having the following general formula, comprising: (In the general formula, R ₁ and R ₂ are each independently 1 to
is an alkyl group with 4 carbon atoms, or R ₁ and R ₂ together are an alkylene group with _up to ₅ carbon atoms;
are each independently a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a halogen atom, or X ₁ and X ₂ together are an alkylene group having up to 5 carbon atoms. , or X ₁
is a hydrogen atom, and X ₂ is a monohalobinyl group, a dihalobinyl group, or a dimethylvinyl group, and R is a methyl or ethyl group). The above reacted with methanol or ethanol in essentially anhydrous conditions at a temperature within the range of 80° to 200°C in the presence of sulfuric acid as a reaction catalyst and as a scavenger for the ammonia formed during the reaction. Method. 2. The method according to claim 1, wherein the reaction temperature is within the range of 100° to 200°C. 3. The method according to claim 1 or 2, wherein the reaction is carried out at a pressure in the range of 1 to 5 atmospheres. 4. Claims 1 to 4, wherein the amount of water present in the reaction mixture is 1% by weight or less of the reaction mixture.
The method according to any one of paragraph 3. 5 R ₁ and R ₂ are methyl groups, X ₁ and X ₂ are chlorine or bromine atoms, or methyl groups, or X _{1 is hydrogen atom, and X 2 is} dichlorovinyl group, dibromovinyl group, difluorovinyl group, chlorofluorovinyl or dimethylvinyl group, and R is methyl or ethyl. 6. The method according to any one of claims 1 to 5, wherein the cyclopropanenitrile of formula () is: 2,2,3,3-tetramethylcyclopropanenitrile, 3・3-dimethyl-2-(2,2-dimethylvinyl)cyclopropane nitrile, 3,3
-dimethyl-2-(2,2-dichlorovinyl)cyclopropanenitrile, and 3,3-dimethyl-2-(2,2-dibromovinyl)cyclopropanenitrile.