Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
  • C07C51/42—Separation; Purification; Stabilisation; Use of additives
  • C07C51/487—Separation; Purification; Stabilisation; Use of additives by treatment giving rise to chemical modification

Definitions

• This invention relates to a novel process for preparing the optical isomers of 2,2-dimethyl-3-(2,2-disubstituted vinyl)cyclopropanecarboxylic acids of the general formula (I),
• R 1 and R 2 independently from another, stand tor halogen or a C 1-4 alkyl group
• R 3 means a cyano or carboxamide group.
• 2,2-Dimethyl-3-(2,2-disubstituted vinyl)cyclopropanecarboxylic acids of the general formula (I) are intermediates in the synthesis of highly effective, commercially available insecticides. Due to their two asymmetry centres, the acids of general formula (I) exist in the form of four stereoisomers. It has been stated that the spectra of biological activity of esters
• 2,826,952 ethyl (-)-2-phenylglycinate was used for separating the optical isomers of the acids of general formula (I).
• the diastereoisomeric salt formation was carried out in an aqueous medium and the optically active acids of general formula (I) obtained from the crystaline salt precipitated or from the mother liquor, respectively, were recrystallized from petroleum ether.
• a resolving agent of varying optical purity was used for the salt formation therefore, the optical purity of the acid enantiomers of the general formula (I) was also varying.
• the value of the optical rotatory power given for trans-permethrinic acid (36 °) is lower by about 10% than the highest optical rotatory power known from the literature [DE-PS 2,628,4727.
• the resolving agent used is sensitive to hydrolytic influences and can be regenerated only with a low effectivity.
• both enantiomers of cyclopropanecarboxylic acids of general formula (I) can be obtained as pure, crystalline diastereoisomeric salt by using resolving agents of general formula (II) having the same configuration.
• the invention further relates to our recognition that the salt formation can be realized with a good effectivity by using the resolving agents of general formula (II) in water or in mixtures of water with C 1-4 alcohols. From the point of view of effectivity of the process our observation is important that the racemic acids of general formula (I) are reacted with a lower amount than one equivalent, suitably with a half equivalent amount of the resolving agent of general formula (II); whereas the optically active enantiomeric mixtures of general formula (I) can preferably be purified by a repeated resolution with the resolving agent of general formula (II) being equivalent to the enantiomer being present in an excess. In the course of salt formations the proportion of the acid of general formula (I) not reacting with the resolving agent is maintained in solution in the form of its alkaline metal salt.
• the process according to the present invention comprises reacting a racemic compound of the general formula (I), wherein R 1 and R 2 are as defined above, or a salt thereof with a phenylglycine derivative of the general formula (II), wherein R 3 means a cyano or carboxamide group, or an acid addition salt thereof, separating the member of the diastereoisomeric salt pair, which precipitates in crystalline form, in a manner known per se and liberating by an acid therefrom the optically active acid of general formula (I) containing (1S)
• R 3 in the compound of general formula (II) used means cyano group
• the optically active acid containing (1R) configuration respectively, when R 3 in the compound of general formula (II) used means carboxamide group, repeating, if desired, this operation 1 to 5 times, recovering the diastereoisomeric salt remaining in the mother liquor in a manner known per se and obtaining therefrom the optically active antipode acid of general formula (I) in a manner known per se.
• 1 mole of the racemic acid of general formula (I) is dissolved with 1 mole of an alkaline metal hydroxide in water, then the solution of the hydrochloride of the resolving agent of general formula (II) in water or in a mixture of water with a C 1-4 alcohol is added at a temperature between 20 °C and 60 °C.
• the reaction mixture is cooled to a temperature of 0 °C to 25 °C and the crystalline diastereoisomeric salt is separated by filtration.
• the salt obtained contains the (1R) acid enantiomer when (R)-2-phenylglycine amide is used and the (1S) acid enantiomer, respectively, when (R)-2-phenylglycicine nitrile is employed.
• the optically active acid isomers of general formula (I) are liberated from the diastereoisomeric salts by adding a mineral acid and separated by filtration; or they are extracted into a water-immiscible organic solvent and then recovered by evaporating the organic solution.
• the other acid enantiomer is recovered from the filtrate of the salt formation by acidification with a mineral acid after distilling out the alcohol content eventually being present in the solution.
• the process according to the invention can be carried out in such a way that the racemic acids of the general formula (I) are suspended in a mixture of water with a C 1 -4 alcohol, then the resolving agent and the required amount of alkaline metal hydroxide (this is determined so that the total amount of the resolving agent and the alkaline metal hydroxide should be equivalent to the racemic acid) are added and the mixture is heated until complete dissolution, then cooled to a temperature between 0 °C arid 25 °C and the crystalline diastereoisomeric salt is separated by
• the optical purity of the acid enantiomers of general formula (I) obtained is increased by a repeated resolution.
• This repeated resolution is carried out by using (R)-2-phenylglycine amide for (1R) acid isomers and (R)-2-phenylglycine nitrile for (1S) acid isomers, respectively, under the same conditions as in the first salt formation, except that the resolving agent is suitably used in an equivalent or lower amount related to the amount of the enantiomer being present in excess.
• the optical purity of the acid enantiomer of the general formula (I) remaining in the mother liquor of the salt formation can be increased in such a way that the mineral acid addition salt of the resolv ing agent of general formula (II) is directly added to the mother liquor at a temperature of 20 °C to
• the resolving agent is selected in such a way that (R)-2-phenylglycine amide is used for a mother liquor enriched of the (1R) acid isomer; whereas (R)-2-phenylglycine nitrile is employed for a mother liquor enriched of the (1S) acid isomer.
• the nearly racemic acids of the general formula (I) remaining in the course of repeated resolutions are regenerated and again used for resolution.
• the mother liquor of the salt formation is acidified to pH 1 by adding 5 molar hydrochloric acid and the precipitated oily acid is extracted 3 times with 20 ml of chloroform each.
• the combined organic solution is dried over sodium sulfate and evaporated to give 5.1 g of (1R)-trans-chrysanthemic acid as residue,
• (1R)-trans-chrysanthemic acid recovered from the filtrate of the first salt formation is dissolved in 20 ml of methanol, 1.5 ml of 5 molar sodium hydroxide solution and then 3.4 g of (R)-2-phenylglycine amide are added. After diluting the mixture with 10 ml of water and cooling to 0 °C, the salt precipitated is filtered. The wet salt is suspended in 15 ml of water, acidified by adding 5 molar hydrochloric acid and the oily product precipitated is extracted 3 times with 15 ml of chloroform each.
• the mother liquors arising from the salt formations of the repeated resolutions are combined and evaporated.
• the residue is suspended in 15 ml of water and acidified to pH 1 by adding 5 molar
• trans-chrysanthemic acid precipitated is extracted 3 times with 15 ml of chloroform each, after combining the chloroform solution is dried over sodium sulfate and evaporated to give 3.2 g of residue which is nearly racemic trans-chrysanthemic acid,

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• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

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• 1989
  • 1989-01-16 HU HU14089A patent/HU205594B/hu not_active IP Right Cessation
• 1990
  • 1990-01-16 EP EP19900901867 patent/EP0411074A1/de not_active Withdrawn
  • 1990-01-16 WO PCT/HU1990/000005 patent/WO1990008126A1/en not_active Application Discontinuation
  • 1990-01-16 JP JP50195390A patent/JPH03503288A/ja active Pending

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