JPH0517215B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing cyclopropane derivatives.

German Patent Publication No. 2639777 is 2-(2,2
-dihalobinyl)-3,3-dimethylcyclopropanecarboxylic acid is disclosed. This acid, especially in the cis-isomeric form, is a useful intermediate in the preparation of insecticidal active compounds. The disclosed method is based on the formula Starting from the compound (wherein X has various meanings). The starting materials exemplified are trans-
Ethyl 2-acetyl-3,3-dimethylcyclopropanecarboxylate, and in the route described, the geometry of the compound is preserved if no special isomerization step is introduced. In fact, as illustrated by the isomerization example given in the publication where the trans compound used could only be converted into a 70:30 trans:cis mixture, the starting material or the route Isomerization of any of the intermediate compounds within is extremely difficult. This is clearly the most unsatisfactory method of producing cis compounds.

Applicant hereby acknowledges that starting materials of the type exemplified in Publication No. 2,639,777 may be treated in such a way as to permit them to be incorporated into either cis or trans compounds as desired. I found it.

The present invention is based on the general formula (wherein each of R ¹ and R ² independently represents a hydrogen atom or an alkyl group having up to 10 carbon atoms, or R ¹ and R ² together represent an alkylene group having 2 to 5 carbon atoms. (representing a group) or its alkali or alkaline earth metal salt, the general formula (wherein R ¹ and R ² have the meanings given in the general formula and R ³ represents an optionally substituted alkyl group) in the presence of water on an alkali or alkaline earth. A method is provided comprising direct contact with a hypochlorite or hypobromite of a class metal.

R ¹ and R ² may be the same or different, but are preferably the same. Preferably each of R ¹ and R ² represents an alkyl group having 1 to 4, especially 1 or 2 carbon atoms. Most preferably R ¹ and
Both R ² represent a methyl group.

The groups R ³ are preferably up to 6 in the alkyl moiety,
In particular it has up to 4 carbon atoms and any substituents on the alkyl moiety can be chosen, for example, from halogen atoms, alkoxy groups and phenyl groups. Preferably R ³ represents an unsubstituted alkyl group, preferably a primary or secondary group, especially a methyl or ethyl group.

In the process according to the invention, hypochlorites or hypobromites of alkali or alkaline earth metals, such as sodium, potassium, calcium, magnesium or barium, are used. Preferably, hypochlorites are used, especially sodium hypochlorite.

If appropriate, the hypochlorite or hypobromite can be added to the reaction mixture in solid form (eg calcium hypochlorite) or as an aqueous solution.

The method according to the invention preferably ranges from -10 to 80°C.
carried out at temperatures in the range of . Generally between −10 and
It is preferred to initiate the reaction at a temperature in the range of 20°C to avoid the formation of undesired halo species. After an initial reaction period, it may be desirable to increase the temperature of the reaction mixture to promote completion of the reaction.

The method according to the invention is carried out in the presence of water.
It is generally preferred that an inert organic solvent also be present to aid in dissolving the starting materials. This additional solvent may be wholly or partially water-miscible, for example an alcohol, such as ethanol, or water-immiscible, for example a hydrocarbon, such as toluene or benzene. In the latter case,
Phase transfer reaction catalysts such as tetrabutylammonium chloride can be used.

Although the molar ratio of the reactants is not critical, it is generally preferred to use an excess of hypochlorite or hypobromite to the compound of general formula. Preferably, the molar ratio of hypochlorite ion or hypobromite ion to the compound of general formula is from 3:1 to 7:
1, especially in the range of 3.5:1 to 5:1.

Depending on the precise reaction conditions, mono- or di-alkali or alkaline earth metal salts of acids of the general formula are generally formed. If it is desired to produce the free acid, it may be isolated by standard work-up procedures under acidic conditions.

The starting materials for the general formula are CH ₃ CO− and −
It exists in isomeric forms in which the CO ₂ R ³ groups are cis or trans to each other. The relative proportions of these cis and trans isomers in the starting material depend on how the starting material was prepared. for example,
The formula described in Publication No. 2639777:
(CH ₃ ) ₂ S ⁺ − ^- CH−CO ₂ R ³ sulfur ylide and mesityl oxide: (CH ₃ ) ₂ C=CH−CO−CH ₃ are reacted and R ¹ and R ² are both methyl. Processes for preparing compounds of formula almost exclusively yield the trans isomer. The terms cis and trans are used throughout this specification to indicate only the relative position of the _CH3CO- and _-CO2R3 groups and the groups ^to which they are converted. Other isomers may of course exist, for example when R ¹ and R ² have different meanings.

The process of the invention may be carried out using cis or trans starting materials, or any mixture thereof, and generally the configuration is preserved in the resulting acid. The resulting acid or salt, whatever its configuration, has the following formula: (wherein R ¹ and R ² have the meanings given above) can be easily converted into the corresponding cis anhydride.

A preferred embodiment of the method according to the invention is thus:
It also includes an additional step of converting the resulting acid of the formula or its alkali or alkaline earth metal salt to the cis anhydride of the corresponding formula.

A cis acid of the formula or an alkali or alkaline earth metal salt thereof can be readily converted to a cis anhydride of the formula by known techniques, e.g. by mild heating or by treatment with a dehydrating agent such as phosphorous trichloride or acetic anhydride. can.

The trans acid or salt can be prepared by using somewhat more aggressive techniques to induce isomerization to the cis anhydride of the formula, such as converting at least one of the carboxyl groups to an acyl halide or anhydride group, and then thermally It is necessary to induce isomerization to form the cis anhydride of formula.

The anhydride group formed may be an anhydride with another molecule of cyclopropanedioic acid itself, for example generated by heating or by reaction with a dehydrating agent, but preferably it is a mixed anhydride.
This is because thermal isomerization of mixed anhydrides generally occurs at lower temperatures than that required for cyclopropanoic acid's own anhydride.

Functionalization of the carboxyl group to an acyl halide or anhydride group is carried out by known techniques, for example to a phosphorous halide or a phosphorus oxyhalide, or a sulfur oxyhalide, or to an alkyl moiety (as appropriate). This can be carried out by reaction of alkanoic acids having up to 4 carbon atoms with acyl halides or anhydrides. Suitable reactants include _PCl3 , _PCl5 , _POCl3 , _SOCl2 , _CH3COl and ( _CH3CO ) _2O . Preference is given to using acetic anhydride or acetyl chloride. Functionalization can in some cases be carried out under conditions such that intermediate isolation of the acyl halide or anhydride is not required.

The temperature required to induce isomerization depends on which functional derivative of the acid is formed, but generally a temperature of at least 130°C, preferably at least 160°C is used. This temperature can be achieved, for example, by heating the functional derivative under pressure in the presence of a low boiling solvent, by heating the functional derivative in the presence of a high boiling solvent, or by vaporizing the functional derivative. Thus, for example, a trans-acid or its alkali or alkaline earth metal salt is dissolved in an alkanoic acid halide or anhydride, such as acetyl chloride or acetic anhydride, which acts as both reactant and solvent, and to prevent evaporation of the solvent. It can be heated under pressure in a sealed tube or autoclave. Alternatively, the functional derivative can be preformed or formed in situ, dissolved in a solvent having a boiling point at or above the desired temperature, and heated to the desired temperature under atmospheric pressure. . Any aprotic high boiling solvent that is inert to the reaction products may be used for this purpose. For example, N-methylpyrrolidone has been found to be suitable.

Other means of inducing thermal isomerization include passing the functionalized trans compound, optionally in the presence of an inert solvent, through a thermal reaction zone preferably containing an inert contact material. Under these conditions vaporization and isomerization occur. The functionalized starting material is dissolved, if desired, in an inert solvent such as toluene, xylene or petroleum ether and pumped into the reaction zone or in a carrier gas, even if this is one of the abovementioned solvents in gaseous form. or an inert gas such as nitrogen). The reaction zone, which is heated to a temperature of preferably 250 to 350° C., is suitably filled with an inert contact material, preferably a mechanically strong material with good thermal conductivity. Glass, alpha alumina and carborundum are suitable.

By appropriate selection of reaction conditions, it is possible to carry out the reaction starting from a compound of the general formula to prepare the cis anhydride of the general formula without intermediate isolation and purification of the intermediate acid or its salt.

The resulting compounds of general formula can be converted to the corresponding cis-2-(2,2-dihalobinyl)cyclopropanecarboxylic acids by a number of routes. The following sequence of reactions is included for illustrative purposes only. For simplicity, only the preparation of 2-(2,2-dichlorovinyl)-3,3-dimethyl cyclopropanecarboxylic acid is described, but similar methods can be used for other compounds.

The anhydride of formula (a) is reacted with sodium trichloroacetate, preferably at a temperature in the range of -60 to 60°C, in the presence of a solvent such as acetonitrile to form cis-2-trichloroacetyl-3,
An equilibrium mixture of 3-dimethylcyclopropanecarboxylic acid and its lactol tautomer is prepared.

(b) This tautomeric mixture is reacted with sodium borohydride in an aprotic solvent such as dimethylformamide at elevated temperature to give the formula: lactone is produced.

(c) Reacting the lactone with a strong base such as potassium tert-butoxide in dimethyl sulfoxide to give the desired cis-2-(2,2-dichlorovinyl)-
3,3-dimethylcyclopropanecarboxylic acid is produced. Trans acids may be prepared by: (a) reacting the tautomeric mixture produced in step (a) above with phosphorous trichloride and zinc in the presence of an inert polar solvent such as dimethylformamide; Formula: to produce lactones.

(b) Hydrolyzing the lactone in the presence of methanol under alkaline conditions to give methyl trans-2-dichloroacetyl-3,3-dimethylcyclopropanecarboxylate.

(c) Reducing this to the corresponding alcohol, namely methyl trans-2-(2,2-dichloro-1-hydroxyethyl)-3,3-dimethyl-cyclopropanecarboxylate.

(d) The alcohol is reacted with tris(dimethylamino)phosphine [N(CH ₃ ) ₂ ] ₃ P and carbon tetrachloride to form a transester, i.e. trans-2-
Methyl (2,2-dichlorovinyl)-3,3-dimethylcyclopropanecarboxylate is produced.
This can be hydrolyzed to the corresponding trans acid under known conditions.

The invention thus also relates to the general formula: (wherein each Hal independently represents a fluorine, chlorine or bromine atom), the method includes the step of converting the compound of the general formula into a compound of the general formula or a salt thereof by the method of the present invention, and A process is provided comprising the use of an anhydride of the formula as produced by the process of the invention for the production of dihalovinylcyclopropanecarboxylic acid, particularly the cis isomeric form of such acid.

The invention is further illustrated by the following examples.

Example 1 Trans-3,3-dimethylcyclopropane-
Production of 1,2-dicarboxylic acid.

Produced by reacting ylide: _C2H5O.CO.CH -S ( _CH3 ) ₂ and mesityl oxide: ( _CH3 ) _2C = _CH -CO- _CH3 in toluene,
and 65% w trans-2-acetyl-3,3
1.5 g of a mixture containing ethyl -dimethylcyclopropanecarboxylate (5.3 mmol) was dissolved in 3 ml of ethanol and cooled in an ice/water bath.
Next, sodium hydroxide (0.5 g, 12.5
21 g of a cold aqueous solution of sodium hypochlorite containing 1.55 mmol per gram of hypochlorite were added dropwise with stirring. Stirring was continued for 1 hour and then the temperature was gradually increased to 60°C and kept at that level for 1 hour. The mixture was then allowed to cool, extracted with dichloromethane, acidified to PH1 with concentrated HCl, saturated with sodium chloride, and extracted with diethyl ether. The ether extracts were combined, washed with brine, dried over magnesium sulphate and evaporated under reduced pressure. The residue contains 0.60 g (72% yield) of trans-3,3-dimethylcyclopropane-1,2-dicarboxylic acid.

Example 2 The procedure described in Example 1 was repeated with the following changes: No sodium hydroxide solution was added, instead water 7
ml was added and heating at 60°C was done for 2 hours instead of 1 hour.

trans-3,3-dimethylcyclopropane-
0.62 g (yield 74%) of 1,2-dicarboxylic acid was obtained.

Example 3 (Reference example) Cis-3,3-dimethylcyclopropane-1,
Preparation of 2-dicarboxylic acid anhydrides.

trans-3, obtained as described in Example 1;
1.2 g (7.6 mmol) of 3-dimethylcyclopropane-1,2-dicarboxylic acid was dissolved in acetyl chloride at room temperature.
3.5 g (45 mmol). After the resulting mixture was boiled for 2 hours under stirring, excess acetyl chloride was removed by distillation under reduced pressure (20 mmHg). N-methylpyrrolidone (4 ml) was added to the residue and the resulting mixture was heated to 200° C. in 30 minutes with stirring under nitrogen atmosphere and kept at this temperature for 1 hour. After cooling to ambient temperature, most of the solvent was removed by distillation under reduced pressure (1 mmHg) in a rotating band column. The residue contains 0.95 g of cis 3,3-dimethylcyclopropane-1,2-dicarboxylic acid anhydride.

Example 4 (Reference example) Cis-3,3-dimethylcyclopropane-1,
Preparation of 2-dicarboxylic acid anhydrides.

trans-3, obtained as described in Example 1;
1.5 g of 3-dimethylcyclopropane-1,2-dicarboxylic acid was dissolved in 4 ml of acetyl chloride at 60°C.
After further heating at 60° C. for 1 hour, volatiles were evaporated under reduced pressure. The residue was dissolved in toluene to make a 10 ml solution. This solution was pumped (3.2 ml/h) at a temperature of 300° C. into a glass tube filled with glass pieces.
A stream of nitrogen was kept flowing through the tube during the experiment. The product stream was condensed. It was found that the main component contained cis-3,3-dimethylcyclopropane-1,2-dicarboxylic acid anhydride (yield 25%).

Example 5 (Reference example) Cis-3,3-dimethylcyclopropane-1,
Preparation of 2-dicarboxylic acid anhydrides.

40 mg each of trans-3,3-dimethylcyclopropane-1,2-dicarboxylic acid and acetic anhydride
Three glass ampoules containing 0.15 g were placed in an oil bath at a temperature of 220°C. The tubes were then removed from the bath after 1/2, 1 and 2 hours.

NMR analysis of the contents revealed that all tubes were cis-3,
It was shown that the anhydride of 3-dimethylcyclopropane-1,2-dicarboxylic acid was contained as the only cyclopropane derivative and that no decomposition products were formed.

Claims (1)

[Claims] 1. General formula (wherein each of R ¹ and R ² independently represents a hydrogen atom or an alkyl group having up to 10 carbon atoms, or R ¹ and R ² together represent an alkylene group having 2 to 5 carbon atoms. (representing a group) or its alkali or alkaline earth metal salt, the general formula (wherein R ¹ and R ² have the meaning given in the general formula and R ³ represents an optionally substituted alkyl group) and an alkali or alkaline earth metal hypochlorite. A process consisting of direct contact of chlorate or hypobromite in the presence of water. 2. Claim 1 in which each of R ¹ and R ² represents an alkyl group having 1 to 4 carbon atoms.
The method described in section. 3. The method according to claim 2, wherein R ¹ and R ² both represent a methyl group. 4. A process according to any of claims 1 to 3, wherein ^R3 represents an unsubstituted alkyl group having up to 6 carbon atoms. 5. The method according to any one of claims 1 to 4, which uses sodium hypochlorite. 6. A method according to any one of claims 1 to 5, carried out at a temperature in the range -10 to 80<0>C. 7 The molar ratio of hypochlorite ion or hypobromite ion to the compound of the general formula is 3:1 to 7:
7. A method according to any one of claims 1-6 within the scope of 1.