DK158304B - METHOD OF STEREOSPECIFIC DECARBOXYLATION OF DIHALOGENVINYLYCYCLOPROPANCARBOXYL ACIDS - Google Patents

Description

DK 158304 B

The present invention relates to a particular method for stereo-specific decarboxylation of dihalo vinylcyclopropane carboxylic acids.

Synthetic pyrethroid insecticides are esters consisting of an acid moiety and an alcohol moiety. In one group of pyrethroids, the acid moiety is derived from a 2,2-dihalovinylcyclopropane carboxylic acid. Such an acid exists in the form of geometric isomers in which the 2,2-dihalovinyl and carboxyl group can sit cis or trans relative to one another. Synthetic pyrethroids, in which the acid moiety is in cis form, often have greater insecticidal activity than the corresponding trans-compounds, and a great deal of research has been directed to the preparation of the specific geometric isomers of 2,2-dihalovinylcyclopropane carboxylic acids.

U.S. Patent No. 4,228,299 and British Patent No. 1,580,203 disclose that 1-cyano-2- (2,2-dihalovinyl) -3,3-dimethylcyclopropanes can be prepared by decarboxylating the corresponding 1-cyano -1-carboxylic acid or a salt thereof by heating in a polar aprotic solvent. The resulting cyano compound can, of course, be converted to the corresponding acid or ester thereof by hydrolysis or alcoholysis.

This process results in high chemical yield and is fully satisfactory for the preparation of compounds in which the ratio of the two possible obtained geometric isomers is not of critical importance. However, it is often desirable to carry out the reaction while maintaining the steric configuration, especially when using a starting material containing a larger portion of one geometric isomer, for example, as shown below for one of the two possible isomers: H CH = CH - 9 2 H "'* CH = CHal0" sJ-a- CH ohb CHj' CO2H CH3 h cis

DK 158304B

2

Unfortunately, in practice, decarboxylation always takes place with some degree of inversion of the stereochemistry, whereby in the example illustrated above, the second isomer is also formed: H- __ -CH = CHal2 cW_ \ h CH3 'di trans 5

Thus, the use of a starting material containing a greater portion of a desired steric configuration usually results in a product containing a substantially lower portion of the corresponding decarboxylated compound in this steric configuration. For example, in the practice of the preferred embodiment of the process of U.S. Patent No. 4,228,299 (i.e., decarboxylation in the presence of a copper salt and water), it has been found using a starting material preferably in a specific steric configuration that partial racemization occurs, resulting in a product containing a significantly lower portion of this specific configuration.

It has now, most surprisingly, been found that maintaining the steric configuration during the decarboxylation process is greatly improved by the performance of the reaction in the presence of water but in the absence of a copper salt.

The present invention therefore relates to a particular process for the preparation of a nitrile of the general formula I

Å = CHal2

-CN I

ch3 H

Wherein each Hal independently represents fluorine, chlorine or bromine, by decarboxylating a carboxylic acid of the general formula II

DK 158304 B

3 XCH = CHal2

RCN

CH 3 COOH or a salt thereof in which Hal is as defined above, the carboxylic acid of general formula II containing at least 70% of the isomer wherein -COOH and dihalo vinyl are trans relative to each other, the process being characterized by that the steric configuration of the carboxylic acid of general formula II is substantially retained in the nitrile of general formula I by performing the decarboxylation without the addition of copper salts and in the presence of 10 water.

Each Hal preferably represents the same halogen, especially chlorine.

For example, if the starting material of general formula II is used in the form of a salt, this may be an alkali metal salt or an optionally alkyl-substituted ammonium salt.

The process according to the invention is carried out as stated in decarboxylation of carboxylic acids containing at least 70% of the trans configuration, namely in the conversion of

H CH = CHal2 CH3 CN

ch3 £ ooh ih 20 to the corresponding stereoisomer of the nitrile, which is called the cis-isomer

DK 158304 B

4 CH = CHal2

CH3 ~ 7 ~ -CN

It should be noted that although the nomenclature changes from trans to cis, the actual steric ratio of all substituent groups remains the same. This apparent inconsistency is due to the application of the IUPAC nomenclature rules which prescribe that geometric isomers should be designated cis or trans with respect to the relative positions of the major substituents at the current sites. Thus, in the acid of the general formula III, the largest substituents are the groups -CH = CHal 2 ° § -COOH, which are trans relative to each other in the illustrated isomer. But the decarboxylation removes the substituent -COOH and leaves -CN as the substituent whose location relative to -CH = CHal2 determines the nomenclature.

The relative proportions of the geometric isomers of the compound of general formula I in which the group -CN sits cis or trans to the dihalo vinyl group depend on the precise reaction conditions and, of course, the ratio, of the corresponding isomer of the carboxylic acid of general formula II, in which the groups -COOH and dihalogenvinyl are trans or cis respectively to each other. In general, there will be a certain decrease in the proportion of the dominant isomer during the process of the invention, but this decrease is far less severe than in the prior art methods. The carboxylic acid of general formula II preferably contains at least 80% of the desired isomer. Particularly preferred is the use of a carboxylic acid of the general formula II which contains a larger proportion of the isomer in which the groups -COOH and dihalo vinyl are trans relative to each other, i.e. the above isomer of the general formula III.

The process according to the invention is preferably carried out in the presence of a supplementary polar organic solvent. Suitable solvents include amides, e.g., dimethylformamide, dimethylacetamide, N-methylpyrrolidone and hexamethylphosphoric triamide; sulfur-containing compounds, for example, dimethyl sulfoxide and sulfolane; amines, e.g., dimethyl-aniline, pyridine and picoline; and nitriles, e.g., acetonitrile. Amides are particularly suitable solvents.

5 The amount of water present in the system is not very critical, although the use of larger amounts of water can lead to the formation of larger quantities of by-products. It is therefore preferred to use water in a molar ratio to the compound of general formula II in the range of 0.5: 1 to 15: 1, especially 1: 1 to 10: 1.

For example, the temperature of the reaction may be in the range of 100-200 ° C, especially 120-160 ° C, and when an organic solvent is used, the temperature is suitably the reflux temperature of the reaction mixture. In some cases, especially when relatively large quantities of water are used, the boiling point of the reaction mixture at atmospheric pressure may be lower than the desired reaction temperature. In this case, the reaction is advantageously carried out under pressure, e.g., a pressure of up to approx. 16 bar.

The method of the invention is preferably carried out in the presence of a base. Suitable bases are weak organic or inorganic bases, e.g., salts of carboxylic acids, especially alkanoic acids such as sodium acetate; ammonia or amines such as triethylamine; alkali metal fluorides, e.g., potassium fluoride; and carbonates and bicarbonates such as sodium carbonate. The amount of base added is not critical, but the number of equivalents of base per moles of compound of the general formula II are preferably in the range 0.5-10, especially 1-5. It may be desirable to carry out the reaction in the presence of a buffer since very strongly basic conditions can lead to some by-product formation by dehydrohalogenation of the dihalo vinyl group, giving the corresponding acetylene group -C = CHal.

The water may be added to the reaction mixture as such or it may be formed in situ, for example, by the reaction of an acid with a base. For example, as discussed above, the reaction may be carried out in the presence of a salt of a carboxylic acid. This salt can be formed with water by the reaction of a carboxylic acid with a base. Thus, for example, the addition of eddi

DK 158304 B

6 hydrochloric acid and sodium hydroxide for the reaction mixture form the necessary water and the preferred base, namely sodium acetate.

The carboxylic acid of general formula II may be added to the reaction mixture as such, or it may be formed in situ, conveniently by dehydrohalogenating a compound of general formula IV

H CHp-CHal2

/ \ IV

CH3 -jL-V-CN

ch3 / \ ooh or a salt thereof, in which each Hal independently represents fluorine, chlorine or bromine, in the presence of a base. Suitable bases include those described above as being useful in the decarboxylation process of the invention, as well as strong bases such as alkali metal hydroxides or alkoxides, e.g., sodium hydroxide. In a preferred embodiment of the process of the invention, the carboxylic acid of general formula II is formed in situ by dehydrohalogenating a compound of general formula IV in the presence of a weak base, and the number of equivalents of base per moles of the compound of the general formula IV are in the range of 1.5-11 especially 2-6.

In this way, the subsequent decarboxylation occurs in the presence of the preferred amounts of weak base as discussed above.

The nitrile compound of general formula I prepared by the process of the invention can be converted to the corresponding acid or salt, ester or amide thereof by known hydrolysis and alcohol methods. Depending on the specific reaction conditions used in the process of the invention, some or all of the resultant compound of general formula I can be hydrolyzed to the corresponding amide or acid or salt thereof in situ, especially in the presence of relatively high concentrations of water. The preparation of such hydrolysis products in situ should be understood as being within the scope of the present invention and may in some cases be a preferred embodiment of the process of the invention.

DK 158304 B

7

Generally, however, maximum yields will be obtained by carrying out the process of the invention under conditions such that the hydrolysis does not occur to any significant extent, and the resulting product is then, if desired, hydrolyzed under conditions optimal for the hydrolysis following an appropriate reprocessing procedure. .

The invention is illustrated by the following examples. The following abbreviations are used in the examples:

Compound A: 1-cyano-2,2-dimethyl-3- (2,2,2-trichloroethyl) cyclopropanecarboxylic acid, trans isomer: i.e. with the group CO2H trans relative to -CH2CC13.

Compound B: 1-cyano-2,2-dimethyl-3- (2,2-dichlorovinyl) cyclopropane carboxylic acid, trans isomer; i.e. with the group CO2H trans relative to the group -CH = CCl2 · Compound C: 1-cyano-2,2-dimethyl-3- (2,2-dichlorovinyl) cyclopropane cis isomer; i.e. with the CN group cis relative to the group -CH = CC12.

EXAMPLE 1

A 1 liter reflux-equipped glass reactor was charged with sodium acetate (90.2 g, 1.1 mole), acetic acid (6.0 g, 0.1 mole), dimethylformamide (415 g), water (24, 0 g, 1.33 mol) and compound A (90.1 g, 0.33 mol) with a trans: cis ratio of 87:13. The stirred mixture was heated to reflux temperature (136 ° C) for 18 hours, after which time the reaction by gas-liquid chromatography was found to be complete. The mixture was then cooled to 25 ° C and 25.7 g of 36 wt% aqueous hydrochloric acid were introduced. The resulting precipitate of sodium chloride was filtered off and washed with dimethylformamide. The combined filtrates were subjected to flash distillation under reduced pressure to remove easily volatile compounds. The residual solution was treated with 100 g of dichloro-ethane, then the organic phase was washed twice with sodium carbonate solution and once with water, followed by flash distillation.

DK 158304 B

8 was cleaved under reduced pressure to isolate the desired product.

Compound C was obtained (0.28 mol, corresponding to a yield of 85%) with a cis: trans ratio of 80:20.

EXAMPLES 2-4 The general procedure described in Example 1 was repeated except that the amount of water added was varied. This resulted in a variation of the reflux temperature as well as the time it took for the reaction to end. These parameters and the results of the experiments are shown in Table I.

TABLE 1

Example H2O added Back Response Reaction Compound C formula (moles per ling temp., Set no. Moles of compound, ° C hours cis: trans yield A) ratio te,% 2 1.0 148 6 75:25 80 3 2.0 145 8.5 78:22 80 4 6.0 133 30 82:18 80 20 EXAMPLE 5

The procedure of Example 1 was repeated except that no dimethylformamide was added and the reaction was carried out using water (25 moles) as solvent. The reaction was carried out at a pressure of 4 bar at a reflux temperature of 140 ° C for 100 hours. Then the cis: trans ratio obtained of compound C was 84:16. In addition to Compound C, however, a considerable amount of other products had also been obtained, the yield of Compound C being approx. 40%.

DK 158304 B

EXAMPLE 6

The procedure of Example 1 was repeated except that compound B was used in place of compound A (trans: cis ratio 87:13) and no sodium acetate or acetic acid was added. Cis: trans ratio of compound C was 74:26. EXAMPLE 7

Following the general procedure of Example 6, compound B was decarboxylated in the presence of different amounts of water and at different reaction temperatures (reflux temperatures).

The results of these experiments are shown in Table 2.

TABLE 2

Added water (mol / mol Reaction Reaction time Compound C formed compound B) temperature (hours) cis: trans% yield - 15 ° C ratio tea 1.0 140 6 75:25 80 2.0 145 8.5 78:22 80 4.0 136 18 80:20 81 20 6.0 133 30 82:18 80 20.0 120 260 84:16 57.5

Comparative Examples Comparative Example A

The procedure of Example 1 was followed except that no water was added. The reflux temperature was 150-155 ° C and the reaction time was 6 hours. The yield of compound C was 78% and the cis: trans ratio was 65:35.

Claims (8)

A process for the preparation of a nitrile of the general formula IH CH = CHal 'λ CH3 - J--V-.CN ch3' \ wherein each Hal is independently fluorine, chlorine or bromine, by decarboxylating a carboxylic acid the general formula II H = CHal = CHal X CH3 - / CN CN COOH or a salt thereof, in which each Hal is as defined above, the carboxylic acid of general formula II containing at least 70% of the isomer, wherein -C00H and dihalo vinyl are trans relative to each other, characterized in that the steric configuration of the carboxylic acid of general formula II is substantially retained in the nitrile of general formula I by performing the decarboxylation without the addition of copper salts and in the presence of water. Process according to claim 1, characterized in that each Hal represents chlorine. Process according to claim 1 or 2, characterized in that the decarboxylation is carried out by heating in the presence of a polar organic solvent. Process according to claim 3, characterized in that the polar organic solvent is an amide. Process according to any one of the preceding claims, characterized in that the molar ratio of water to the carboxylic acid of the general formula II or a salt thereof is. in the range of 1: 1 to 10: 1. Process according to any one of the preceding claims, characterized in that the decarboxylation is carried out by heating to a temperature in the range of 100-200 ° C. DK 158304 B 12 Method according to any one of the preceding claims, characterized in that it is carried out in the presence of a base. Process according to any one of the preceding claims, characterized in that the starting material is formed in situ by dehydrohalogenation, in the presence of a base, of a compound of the general formula IV Hv. CH2-CHal3 CH3 / \ CN IV CH3 \ cooh or a salt thereof, in which Hal is as defined in claim 1.