DK158343B - METHOD OF PREPARING METHYL OR ETHYLYCYCLOPROPANCARBOXYL ACID ESTERS - Google Patents

Description

DK 158343 B

The present invention relates to a process for preparing methyl or ethylcyclopropane carboxylic acid esters of the general formula described in the preamble of claim 1.

Substituted cyclopropane carboxylic acids are useful intermediates in the preparation of pesticide-active esters thereof, especially the 3-phenoxybenxyl and α-cyano-3-phenoxybenzyl esters; these pesticide-active compounds, the so-called "synthetic pyrethroids" have exceptionally good insecticidal properties, while having a very low mammalian toxicity. This combination of properties makes them particularly interesting for the agrochemical industry, and great efforts have been made to find economical routes for these "synthetic pyrethroids", especially for the production of substituted cyclopropane carboxylic acids, for which no synthetic materials have been mentioned so far. manufacturing pathways in the literature.

In the search for economical routes of production for the cyclopropanecarboxylic acid, it has succeeded in synthesizing the substituted cyclopropanitrile, but it has hitherto been impossible to successfully convert the nitrile to the corresponding acid or ester.

Alcoholysis in the presence of an acid catalyst according to the many recommendations in standard text books has been attempted, but the yield of the corresponding alkyl ester is very poor and often results in the production of large quantities of lactones and other by-products.

It is known to convert nitriles to esters by the "Pinner" reaction (see "Houben-Weyl Handbuch der Organischen Chemie", H.

25 Heneka, Book 8, pages 536-539 (1952) and "Chemical Reviews", Robert

Roger and Douglas Neilson, pages 181-184 (1961)), which involve reacting a nitrile with an alkanol and hydrogen bromide or chloride at ambient temperature or under cooling under anhydrous conditions, followed by hydrolysis of the resulting water-sensitive imino ether.

However, for cyclopropanitriles, the "Pinner" reaction conditions have no effect, even after a period of 24 hours.

DK 158343 B

2

It has now surprisingly been found that a modification of the "Pinner" conditions results in a simple conversion of a substituted cyclopropannitrile to the methyl or ethyl ester thereof.

The present invention therefore relates to a process for the preparation of methyl or ethylcyclopropane carboxylic acid esters of the general formula I

X1 x2 R1 / COOR τ

R2 H

10 wherein kA and independently each represent alkyl of 1-4 carbon atoms, or and R sammen together represent the alkyl of up to 5 carbon atoms, X ^ and X ^ independently each represent hydrogen, alkyl of 1-4 carbon atoms or halogen or or together represent alkylene of up to 5 carbon atoms, or X X represents hydrogen, and represents monohalogenvinyl, dihalogenvinyl or dimethylvinyl, and R represents methyl or ethyl which is characterized by a cyclopropannitrile having the general formula II

X1 X2

R1 / V-- CN II

R2 H

20 is reacted with methanol or ethanol under substantially anhydrous conditions whereby the amount of water present in the reaction mixture is less than 5% by weight thereof, at a temperature in the range of 80-200 ° C and in the presence of sulfuric acid which acts as a reaction catalyst and which means for removing the ammonia formed during the reaction.

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DK 158343B

The reaction temperature is preferably maintained in the range 100-200 ° C, more advantageously in the range 140-200 ° C. With the reaction mixtures used in the process of the present invention, temperatures in the required range will usually not be attainable at atmospheric pressure, and thus higher pressures, e.g. in the range of 1-10 atmospheres, in general, pressures in the range of 1-5 atmospheres have been found to be sufficient.

As stated above, it has been found necessary to use essentially anhydrous conditions, i.e. conditions under which the amount of water present during the reaction is kept to a minimum, namely below 5% by weight of the reaction mixture, preferably below 1% by weight and suitably below 0.5% by weight of the reaction mixture.

Eg. For example, the amount of water normally present in concentrated sulfuric acid (2% by weight) at the acid concentrations used in the process can be tolerated, provided that the alcohol and nitrile reactants are substantially dry.

As the reaction proceeds, ammonia is formed which neutralizes the acidic catalyst and thus sufficient amounts of acid must be present to provide the necessary catalytic action. In general, the amount of acid present (based on the weight of the nitrile) in the process of the present invention should be in the range of 3: 1-1: 1.

In the alcoholysis reaction, it has been found that only the ethanol and methanol under the above conditions give the corresponding ester of the nitrile of the general formula II in satisfactory yields and in the substantial absence of undesirable by-products. Ethanol is the preferred reagent because of the relatively short reaction time involved in ethanolysis in the process of the present invention, and also because of the economic advantage of using such an readily available product.

Of the compounds of the general formula I, those are preferred wherein R 1 and R 2 represent methyl, X 2 and X 2 represent chloro, bromo or methyl, or X 2 represents hydrogen and X 2 represents dichlorovinyl.

DK 158343 B

4 represents dibromovinyl, difluorovinyl, chlorofluorovinyl or dimethylvinyl, and R represents methyl or ethyl.

As indicated above, the alcoholysis reaction enables the conversion of a cyclopropannitrile to the corresponding methyl or ethyl ester, which can then be converted to a "synthetic pyrethroid" via the free acid or acid chloride by reaction with 3-phenoxybenzyl alcohol or α-cyano-3- phenoxybenzylalcohol. The following nitriles are the most important because they are intermediates for the pyrethroids with the greatest pesticidal action: 2,2,3,3-Tetramethylcyclopropannitrile, 3,3-dimethyl-2- (2,2-dimethylvinyl) cyclopropannitrile, 3.3 -dimethyl-2- (2,2-dichlorovinyl) cyclopropannitrile and 3,3-dimethyl-2- (2,2-dibromo-vinyl) cyclopropannitrile.

It will be appreciated that since the nitrile starting products and the ester end products of the process of the present invention have asymmetric carbon atoms, the nitriles and esters may exist in a similar number of stereoisomeric forms. Therefore, the process of the present invention also encompasses the preparation of compounds of general formula I which are in the form of single stereoisomers or mixtures thereof.

The process of the present invention is further illustrated by the following Examples: EXAMPLE 1

Preparation of methyl 3,3-dimethyl-2- (2,2-dichlorovinyl) cyclopropane carboxylate

A mixture of 2.0 g (0.11 mol) of essentially dry 3,3-dimethyl-2- (2,2-dichlorovinyl) cyclopropannitrile and 12 ml of sulfuric acid / methanol solution (20% by weight concentrated sulfuric acid in dry methanol) autoclaved at 100 ° C (5 atmospheres) for 32 hours. 30 water is then added and the product is extracted with methylene chloride. The organic 5

DK 158343B

phase is washed with dilute sodium bicarbonate solution, dried over magnesium sulfate and evaporated to give methyl 3,3-dimethyl-2- (2,2-dichlorovinyl) cyclopropane carboxylate (95% conversion, 100% selectivity against the methyl ester).

EXAMPLES 2-4

Preparation of ethyl 3,3-dimethyl-2- (2,2-dichlorovinyl) cyclopropane carboxylate

The procedure of Example 1 is repeated using ethanol instead of methanol as an alcoholic reagent and using 10 different nitrile concentrations. The reaction conditions and results are listed in Table A.

Table A

Eczema- Alcohol H2S04 / - DCVN1 Temp- Pressure Time Conversion- Selective alcohol concentration (atmospheric (titled 15 no. Ratio trip)) of DCVN (%) (w / w) % (w / v) (eC) (%) II ethanol 1: 4 7 160 5 4.5 99 97 III ethanol 1: 4 14 170 5 6.0 98 99 20 IV ethanol 1: 4 20 170 4 10.0 97 99 DCVN = 3,3-dimethyl-2- (2,2-dichlorovinyl) cyclopropanitrile. Comparative Examples 25 A number of comparative experiments are carried out using methanol, ethanol, isopropanol and n-butanol as alcoholic reagent and three different acid catalysts; the same nitrile (DCVN) is used as in the previous examples.

The reaction conditions and results are listed in Table B.

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DK 158343B

It can be seen that the yields of DCVA esters are considerably lower than those obtained by the process of the present invention, and are also inevitably accompanied by unwanted by-products, in particular the corresponding amide and a lactone by-product, the latter being due to presumably acid-catalyzed ring opening followed by alcoholysis and ring closure to form a lactone. Moreover, for the ethanolysis, the reaction time is also much longer than in the method used in Examples 2-4.

DK 158343B

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Claims (6)

A process for the preparation of methyl or ethylcyclopropane carboxylic acid esters of the general formula I 1 2 Y R1-J --- COOR T 5 wherein R 2 and R 2 independently each represent alkyl of 1-4 carbon atoms, or R - and together represent alkylene of up to 5 carbon atoms, X 2 and X 2 independently each represent hydrogen, alkyl of 1-4 carbon atoms or halogen, or X 2 - and X 3 together represent alkylene of up to 5 carbon atoms or X X represents hydrogen and X ^ represents monohalo genvinyl, dihalogenvinyl or dimethyl-vinyl, and R represents methyl or ethyl, characterized in that a cyclopropannitrile of general formula II is 15 χ1 γ2 λ R1 / -VcN yh where R -, R 2, X 2 - and X 2 have the above meanings, reacted with methanol or ethanol under substantially anhydrous conditions whereby the amount of water present in the reaction mixture is less than 5% by weight thereof, at a temperature in the range of 80 -200 ° C and in the presence of sulfuric acid, so m acts as a reaction catalyst and as a means of removing the ammonia formed during the reaction. DK 158343B Process according to claim 1, characterized in that the reaction temperature is in the range 100-200 ° C. Process according to claim 1 or 2, 5, characterized in that the reaction is carried out at a pressure in the range 1-5 atmospheres. Process according to any one of the preceding claims, characterized in that the amount of water present in the reaction mixture is less than 1% by weight thereof. Process according to any one of the preceding claims, characterized in that compounds of the general formula I are prepared, wherein rA and denoting methyl, X * and X 2 represent chloro, bromo or methyl, or X * - hydrogen, and represents dichlorovinyl, dibromovinyl, difluorovinyl, chlorofluorovinyl or dimethylvinyl, and R represents methyl or ethyl. Process according to any one of the preceding claims, characterized in that the cyclopropannitrile of general formula II used is 2,2,3,3-tetramethylcyclopropannitrile, 3,3-dimethyl-2- (2,2). -dimethylvinyl) cyclopropannitrile, 3,3-dimethyl-2- (2,2-dichlorovinyl) cyclopropannitrile or 3,3-dimethyl-2- (2,2-dibromonyl) cyclopropannitrile.