JPH0323539B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to stereospecific decarboxylation of dihalovinylcyclopropanecarboxylic acids. Synthetic pyrethroid insecticides are esters consisting of an acid part and an alcohol part. In one group of pyrethroids, the acid moiety is derived from 2,2-dihalovinylcyclopropanecarboxylic acid. Such acids exist in the form of geometric isomers,
In this case, the 2,2-dihalobinyl group and the carboxyl group may be mutually cis or trans. Synthetic pyrethroids, in which the acid moiety is in the cis form, often have greater insecticidal activity than the corresponding trans compounds, and considerable research has shown that
Attempts have been made to produce unique geometric isomers of 2,2-dihalovinylcyclopropanecarboxylic acid. US Pat. No. 4,228,299 and British Patent No. 1,580,203 disclose that 1-cyano-2-(2,2-dihalobinyl)-3,3-dimethylcyclopropane is a corresponding 1-cyano-1-carboxylic acid or It is disclosed that the salt can be prepared by heating and decarboxylating the salt in a polar neutral solvent. The resulting cyano compound can of course be converted into the corresponding acid or its ester by hydrolysis or alcoholysis. The process proceeds with high chemical yields and
The proportion of the two possible geometric isomers obtained is completely satisfactory for the preparation of compounds of no critical importance. However, it is often desirable to proceed with the reaction while preserving the configuration, and in particular this may be the case if starting materials containing a large proportion of one geometric isomer to one of the two possible isomers, e.g. When using: Unfortunately, in practice decarboxylation usually proceeds with some inversion of stereochemistry, and in the cases indicated above other isomers are also formed: Therefore, the use of a starting material containing a large proportion of the desired configuration usually results in a product containing a much smaller proportion of that configuration in the corresponding decarboxylated compound. For example, when carrying out the preferred example of US Pat. No. 4,228,299 (i.e., decarboxylation in the presence of copper salts and water) with starting materials predominantly in a particular configuration, partial racemization occurs and significantly It has been found that products containing a low proportion of the particular configuration are produced. Very surprisingly, it has been found that configurational preservation during decarboxylation is greatly improved by carrying out the reaction in the presence of water and in the absence of copper salts. The present invention is based on the general formula (In the formula, each Hal independently represents a fluorine atom, a chlorine atom, or a bromine atom.) A method for producing a nitrile of the general formula A method for producing a nitrile comprising decarboxylating a carboxylic acid or a salt thereof (wherein each Hal has the above-mentioned meaning), wherein the configuration of the carboxylic acid is different from that of water without the addition of a copper salt. A process for producing the nitrile, characterized in that the nitrile is substantially retained in the nitrile by decarboxylation in the presence of. Preferably each Hal represents the same halogen atom, especially a chlorine atom. If the starting material of the general formula is used in the form of a salt, it may be, for example, an alkali metal salt or an optionally alkyl-substituted ammonium salt. The method of the invention predominantly uses a transformer configuration, i.e.: Decarboxylation of carboxylic acids containing the cis isomer: is of particular value in obtaining the corresponding stereoisomers of the nitriles. Note that although the nomenclature changes from trans to cis, the actual steric relationships of all substituents remain the same. This apparent contradiction is
It arises from the application of the IUPAC nomenclature rules, which state that geometric isomers should be named cis or trans with respect to the position of the largest substituent involved. This is because it has been established. That is, in the acid of formula, the largest substituents are -CH=CHal ₂ and -COOH groups, which are in a trans relationship in the isomer shown. However, decarboxylation -
The COOH substituent is removed, leaving -CN as a substituent whose relationship to -CH= _CHal2 determines the nomenclature. The relative proportions of geometric isomers of compounds in which the -CN group is cis or trans to the dihalobinyl group will depend on the exact reaction conditions and, of course, -
It depends on the proportion of the corresponding isomers of the carboxylic acid of the formula in which the COOH and dihalobinyl groups are mutually trans or cis, respectively. Generally, there may be some reduction in the proportion of the major isomer through the process of the invention, but this reduction is less drastic than in conventional processes. Preferably, the carboxylic acid consists of at least 70%, preferably at least 80%, of derivatized isomers. -An isomer in which the COOH group and the dihalobinyl group are mutually trans,
Particular preference is therefore given to the use of carboxylic acids which contain as a major part an isomer of the above formula. The process according to the invention is preferably carried out in the presence of an additional polar organic solvent. Suitable solvents include: amides such as dimethylformamide, dimethylacetamide, N-methylpyrrolidone and hexamethylphosphortriamide, sulfur-containing compounds such as dimethylsulfoxide and sulfolane, amides such as dimethylaniline, pyridine or picoline. , a nitrile such as acetonitrile. Amides are particularly useful solvents. Although high proportions of water can result in high by-product production, the amount of water present in the system is not very critical. Therefore, the molar ratio of water to the compound of general formula should be between 0.5:1 and 0.5:1.
It is preferable to use a ratio of 15:1, particularly in the range of 1:1 to 10:1. The reaction temperature is, for example, 100 to 200°, especially 120°.
to 160°C, conveniently at the reflux temperature of the reaction mixture when organic solvents are used. In some cases, especially when relatively large amounts of water are used,
The boiling point of the reaction mixture at atmospheric pressure will be lower than the desired reaction temperature. In this case, the reaction is carried out under pressure,
For example, it is advantageously carried out at a pressure of about 16 bar or less. The method according to the invention is preferably carried out in the presence of a base. Suitable bases include: weak organic or weak inorganic bases, such as salts of carboxylic acids, especially alkanoic acids, such as sodium acetate, ammonia or amines such as triethylamine, alkali metal fluorides such as potassium fluoride, carbonic acid. Salts and bicarbonates such as sodium carbonate. Although the amount of added base is not critical, the number of equivalents of base per mole of compound of general formula preferably ranges from 0.5 to 10, especially from 1 to 5. It is desirable to proceed with the reaction in the presence of a buffer because very basic conditions
This is because dehydrohalogenation of the dihalovinyl group may lead to the formation of some by-products, resulting in the corresponding ethylene group -C≡CHal. The water itself may be added to the reaction mixture or may be generated in situ, for example by reaction of an acid with a base. For example, as mentioned above,
The reaction may be carried out in the presence of a salt of a carboxylic acid. This salt may be formed with water by reaction of a carboxylic acid with a base. For example, addition of acetic acid and sodium hydroxide to the reaction mixture yields the requisite water and the preferred base, sodium acetate. The carboxylic acid of the general formula may be added to the reaction mixture as such or alternatively the carboxylic acid of the general formula (In the formula, each Hal independently represents a fluorine atom, a chlorine atom, or a bromine atom.) You can also do this. Suitable bases include: the bases mentioned above as useful in the decarboxylation according to the invention, strong bases such as alkali metal hydroxides or alkoxides, eg sodium hydroxide. In a preferred embodiment of the process according to the invention, carboxylic acids of the general formula are formed in situ by dehydrohalogenation of a compound of the general formula in the presence of a weak base; The number of base equivalents ranges from 1.5 to 11, especially from 2 to 6. In this way, the next decarboxylation is
This occurs in the presence of a preferred amount of a weak base as described above. The nitrile compounds of the general formula prepared by the process according to the invention can be converted into the corresponding acids or their salts, esters or amides by known methods of hydrolysis or alcoholysis. Depending on the exact reaction used in the method according to the invention, some or all of the resulting compounds of formula can be hydrolyzed in situ, in particular in the presence of relatively high concentrations of water.
It may also be a corresponding amide or acid or a salt thereof. The production of such hydrolysis products in situ is to be construed as falling within the scope of the invention, and in some cases even represents a preferred example of the process according to the invention. However, the process according to the invention is carried out under conditions such that hydrolysis does not appreciably occur, and then, after suitable work-up, the resulting product is subjected to conditions optimal for hydrolysis. Maximum yields are obtained by hydrolysis as desired. The present invention will be explained below by giving examples. In each example, the following abbreviations are used: Compound A: 1-cyano-2,2-dimethyl-3-
(2,2,2-trichloroethyl)cyclopropanecarboxylic acid, trans isomer; i.e.
CO ₂ H group is trans to -CHCCl ₃ group. Compound B: 1-cyano-2,2-dimethyl-3-
(2,2-Dichlorovinyl)cyclopropanecarboxylic acid, trans isomer; ie, the _CO2H group is trans to the -CH= _CCl2 group. Compound C: 1-cyano-2,2-dimethyl-3-
(2,2-dichlorovinyl)cyclopropane cis isomer; that is, the CN group is cis to the -CH=CCl ₂ group. Example 1 Sodium acetate (90.2 g (1.1 mol)), acetic acid (6.0 g (0.1 mol)), dimethylformamide (415
g), water (24.0 g (1.33 mol)) and trans:
Compound A (90.1 g (0.33 mol)) with a cis ratio of 87:13
was placed in a glass reactor equipped with a reflux condenser. The mixture was stirred and heated to reflux temperature (136° C.) for 18 hours, after which completion of the reaction was confirmed by gas phase chromatography. The mixture was then cooled and 77.7 g of 36% by weight hydrochloric acid was added.
The resulting sodium chloride precipitate is filtered off and washed with dimethylformamide. The liquids are combined and subjected to flash distillation under reduced pressure to remove volatiles.
The resulting solution was treated with 100 g of dichloroethane,
The organic phase is washed twice with sodium carbonate solution and once with water before flash distillation under reduced pressure to isolate the desired product. Compound C is obtained in a cis:trans ratio of 80:20 (0.28 mol, 85
% yield). Examples 2-4 The procedure set forth in Example 1 was followed except that the amount of water added was varied. This resulted in a change in reflux temperature and time to complete the reaction. These parameters and experimental results are shown in the table.

[Table] Example 5 Example 1 except that the reaction was carried out using water as a solvent instead of dimethylformamide.
The procedure was the same as that of The reaction was carried out for 100 hours at a pressure of 4 bar and a reflux temperature of 140°C. At the end of this time, a cis:trans ratio of Compound C of 84:16 was obtained. However, besides compound C, significant amounts of other products were obtained, with a yield of compound C of about 40%.
It is. Example 6 Compound B to Compound A (trans:cis ratio 87:13)
The procedure was the same as in Example 1 except that no sodium acetate or acetic acid was added. The cis:trans ratio of Compound C was 74:26. Example 7 Following the general procedure of Example 6, Compound B was subjected to various reactions (refluxing) in the presence of various amounts of water.
Decarboxylation occurred at temperature. The results of these experiments are shown in Table 2 below.

[Table] Comparative Example Comparative Example A The procedure was the same as in Example 1, 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 is 78%
The cis:trans ratio was 65:35. Comparative Example B The procedure is similar to A except that the reaction mixture is heated to only 135°C (i.e., below the reflux temperature).
The same as The yield of compound C was 77%, and the cis:trans ratio was 70:30. Comparative Example C The same procedure as Example 1 was followed, except that 0.033 mol of CuSO ₄ .5H ₂ O was further added. The reaction proceeded very quickly and was completed in about 3 hours, and the cis:trans ratio of compound C was 40:60. Comparative Example D The procedure was the same as that of Example 6, except that 0.033 mol of CuSO ₄ .5H ₂ O was further added. After rapid reaction, the cis:trans ratio of compound C was 53:47.

Claims (1)

[Claims] 1. General formula (In the formula, each Hal independently represents a fluorine atom, a chlorine atom, or a bromine atom.) A method for producing a nitrile of the general formula A method for producing a nitrile comprising decarboxylating a carboxylic acid or a salt thereof, in which each Hal has the above-mentioned meaning, wherein the configuration of the carboxylic acid is different from that of water without the addition of a copper salt. A method for producing a nitrile, characterized in that the nitrile is substantially preserved in the nitrile by decarboxylation in the presence of. 2 Carboxylic acid is predominantly trans configuration: 2. The manufacturing method according to item 1 above. 3. The method according to item 2, wherein the carboxylic acid contains at least 70% of the defined trans isomer. 4. The manufacturing method according to item 1, 2 or 3 above, wherein each Hal represents a chlorine atom. 5. The manufacturing method according to any one of items 1 to 4 above, wherein the decarboxylation is performed by heating in the presence of a polar organic solvent. 6. The manufacturing method according to item 5 above, wherein the polar organic solvent is an amide. 7. The manufacturing method according to any one of items 1 to 6 above, wherein the molar ratio of water to carboxylic acid or its salt is in the range of 1:1 to 10:1. 8. The manufacturing method according to any one of items 1 to 7 above, wherein the decarboxylation is carried out by heating at a temperature in the range of 100 to 200°C. 9. The manufacturing method according to any one of items 1 to 8 above, which is carried out in the presence of a base.