+

WO1990008126A1 - Procede de resolution - Google Patents

Procede de resolution Download PDF

Info

Publication number
WO1990008126A1
WO1990008126A1 PCT/HU1990/000005 HU9000005W WO9008126A1 WO 1990008126 A1 WO1990008126 A1 WO 1990008126A1 HU 9000005 W HU9000005 W HU 9000005W WO 9008126 A1 WO9008126 A1 WO 9008126A1
Authority
WO
WIPO (PCT)
Prior art keywords
general formula
acid
salt
compound
phenylglycine
Prior art date
Application number
PCT/HU1990/000005
Other languages
English (en)
Inventor
Ferenc Faigl
Elemér Fogassy
Lajos Nagy
László CSIZ
Irén CZUDOR
Éva KOVÁCSNÉ KOZSDA
Original Assignee
Chinoin Gyógyszer és Vegyészeti Termékek Gyára Rt.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Chinoin Gyógyszer és Vegyészeti Termékek Gyára Rt. filed Critical Chinoin Gyógyszer és Vegyészeti Termékek Gyára Rt.
Publication of WO1990008126A1 publication Critical patent/WO1990008126A1/fr

Links

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,

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Le nouveau procédé décrit sert à préparer les isomères optiques d'acides 2,2-diméthyl-3-(2,2-disubstitué vinyl)cyclopropanecarboxyliques représentés par la formule générale (I), où R1 et R2, séparément l'un de l'autre, représente un halogène ou un groupe alkyle C¿1-4?. Ledit procédé consiste à faire réagir un composé racémique représenté par la formule générale (I), où R?1 et R2¿ sont définis ci-dessus, ou un sel de ce composé avec un dérivé de phénylglycine représenté par la formule générale (II), où R3 représente un groupe cyano ou carboxamide ou un sel d'addition d'acide de ce groupe, à séparer l'élément de la paire de sels diastéréoisomères, qui précipite sous forme cristalline, selon une technique connue en soi, et à libérer de cet élément par un acide l'acide optiquement actif de formule générale (I) présentant la configuration (1S), lorsque R3 dans le composé de la formule générale (II) utilisé représente un groupe cyano, ou l'acide optiquement actif présentant la configuration (1R), respectivement, lorsque R3 dans le composé de la formule générale (II) utilisé représente un groupe carboxamide, à répéter, si nécessaire, cette opération une à cinq fois, à récupérer le sel diastéréoisomère restant dans la liqueur-mère selon une technique connue en soi et obtenir à partir de ce sel l'acide antipodal optiquement actif de formule générale (I) selon une technique connue en soi.
PCT/HU1990/000005 1989-01-16 1990-01-16 Procede de resolution WO1990008126A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
HU14089A HU205594B (en) 1989-01-16 1989-01-16 Process for producing optical isomeres of cyclopropane-carboxylic acids5
HU140/89 1989-01-16

Publications (1)

Publication Number Publication Date
WO1990008126A1 true WO1990008126A1 (fr) 1990-07-26

Family

ID=10948122

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/HU1990/000005 WO1990008126A1 (fr) 1989-01-16 1990-01-16 Procede de resolution

Country Status (4)

Country Link
EP (1) EP0411074A1 (fr)
JP (1) JPH03503288A (fr)
HU (1) HU205594B (fr)
WO (1) WO1990008126A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2061403A1 (es) * 1993-04-16 1994-12-01 Medichem Sa Procedimiento de obtencion del acido d-(-) -3 acetiltio-2- metilpropionico.
WO2018071320A1 (fr) * 2016-10-12 2018-04-19 Dow Agrosciences Llc Procédé de préparation d'acides (1r,3r)- et (1s,3s) -2,2-dihalo-3-(phényle substitué) cyclopropanecarboxylique
US10258045B2 (en) 2016-10-12 2019-04-16 Dow Agrosciences Llc Molecules having pesticidal utility and intermediates, compositions and processes related thereto
US11632957B2 (en) 2015-04-17 2023-04-25 Corteva Agriscience Llc Molecules having pesticidal utility, and intermediates, compositions, and processes, related thereto

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2043173A1 (de) * 1969-09-12 1971-04-29 Sumitomo Chemical Co , Ltd , Osaka (Japan) Verfahren zur Gewinnung von op tisch aktiver (+) Chrysanthemummono carbonsaure aus dem razemischen Gemisch
DE2300325A1 (de) * 1972-01-07 1973-07-12 Sumitomo Chemical Co Verfahren zur herstellung von (+)trans-chrysanthemsaeure
EP0006187A1 (fr) * 1978-06-20 1980-01-09 Bayer Ag Séparation d'énantiomères d'acides carboxyliques chiraux

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2043173A1 (de) * 1969-09-12 1971-04-29 Sumitomo Chemical Co , Ltd , Osaka (Japan) Verfahren zur Gewinnung von op tisch aktiver (+) Chrysanthemummono carbonsaure aus dem razemischen Gemisch
DE2300325A1 (de) * 1972-01-07 1973-07-12 Sumitomo Chemical Co Verfahren zur herstellung von (+)trans-chrysanthemsaeure
EP0006187A1 (fr) * 1978-06-20 1980-01-09 Bayer Ag Séparation d'énantiomères d'acides carboxyliques chiraux

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2061403A1 (es) * 1993-04-16 1994-12-01 Medichem Sa Procedimiento de obtencion del acido d-(-) -3 acetiltio-2- metilpropionico.
US11632957B2 (en) 2015-04-17 2023-04-25 Corteva Agriscience Llc Molecules having pesticidal utility, and intermediates, compositions, and processes, related thereto
US12256738B2 (en) 2015-04-17 2025-03-25 Corteva Agriscience Llc Molecules having pesticidal utility, and intermediates, compositions, and processes, related thereto
WO2018071320A1 (fr) * 2016-10-12 2018-04-19 Dow Agrosciences Llc Procédé de préparation d'acides (1r,3r)- et (1s,3s) -2,2-dihalo-3-(phényle substitué) cyclopropanecarboxylique
US10239817B2 (en) 2016-10-12 2019-03-26 Dow Agrosciences Llc Process for the preparation of (1R,3R)- and (1S,3S)-2,2-dihalo-3-(substituted phenyl)cyclopropanecarboxylic acids
US10258045B2 (en) 2016-10-12 2019-04-16 Dow Agrosciences Llc Molecules having pesticidal utility and intermediates, compositions and processes related thereto
KR20190059291A (ko) * 2016-10-12 2019-05-30 다우 아그로사이언시즈 엘엘씨 (1r,3r)- 및 (1s,3s)-2,2-디할로-3-(치환된 페닐)시클로프로판카르복실산의 제조 방법
CN109863131A (zh) * 2016-10-12 2019-06-07 美国陶氏益农公司 制备（1r，3r）-2,2-二卤代-3-（取代的苯基）环丙烷甲酸和（1s，3s）-2,2-二卤代-3-（取代的苯基）环丙烷甲酸的方法
US10993440B2 (en) 2016-10-12 2021-05-04 Dow Agrosciences Llc Molecules having pesticidal utility, and intermediates, compositions, and processes related thereto
CN109863131B (zh) * 2016-10-12 2022-04-05 美国陶氏益农公司 制备环丙烷甲酸的方法
KR102479201B1 (ko) 2016-10-12 2022-12-20 코르테바 애그리사이언스 엘엘씨 (1r,3r)- 및 (1s,3s)-2,2-디할로-3-(치환된 페닐)시클로프로판카르복실산의 제조 방법
US11944099B2 (en) 2016-10-12 2024-04-02 Corteva Agriscience Llc Molecules having pesticidal utility, and intermediates, compositions, and processes, related thereto

Also Published As

Publication number Publication date
JPH03503288A (ja) 1991-07-25
EP0411074A1 (fr) 1991-02-06
HU205594B (en) 1992-05-28
HUT52472A (en) 1990-07-28

Similar Documents

Publication Publication Date Title
JP2839344B2 (ja) 環状アミノ酸、並びにその中間体の製造方法
US6015903A (en) Method of resolving racemic mixtures
US5677469A (en) Process for resolving chiral acids with 1-aminoindan-2-ols
IL175488A (en) Process for resolving optionally substituted mandelic acids by salt formation with a chiral base cyclic amide
EP0605384B1 (fr) Procédé de purification et d'isolement d'atendol optiquement actif avec un haut rendement
EP0623104B1 (fr) Resolution du profene
CA2623355A1 (fr) Resolution de derives d'acide alpha-(phenoxy) phenylacetique avec des naphtyl-alkylamines
EP3653607B1 (fr) Procédé de préparation de 3-aminopipéridine enrichie sous la forme énantiomère
US3996246A (en) Resolution of racemic pantolactone
US4966996A (en) Process for the preparation of E-2-propyl-2-pentenoic acid and physiologically compatible salts thereof
US5191112A (en) Process for optical resolution of (±)-2-(3-benzoyl)-phenylpropionic acid
WO1990008126A1 (fr) Procede de resolution
JP2004511476A (ja) Ｒ（＋）α−リポ酸の製造方法
US4571424A (en) Optical resolution of racemic femoxetine
JP2011098975A (ja) キラル純ｎ−（トランス−４−イソプロピル−シクロヘキシルカルボニル）−ｄ−フェニルアラニン及びそれらの結晶構造変性体の生成方法
EP0093511B1 (fr) Procédé de production d'un acide 2,2-diméthylcyclopropane carboxylique optiquement actif
US4233456A (en) Process for the manufacture of optically active, optionally substituted 2-amino-2-phenylacetic acid
US4045450A (en) Optical resolution of DL-pantolactone
KR100645277B1 (ko) (+)-트랜스-크리산테뮴-모노카르복실산의 제조방법
US4508919A (en) Process for the preparation of optically active cyclopropane carboxylic acids
US5900492A (en) Method of producing optically active cyclopropane derivatives
JP4093608B2 (ja) 光学活性２−フェノキシプロピオン酸の製造方法
RU2015953C1 (ru) Способ расщепления рацемата 2,2-диметилциклопропанкарбоновой кислоты
EP0441979B1 (fr) Derive d'acide 2-(phenyl a substitution alkyle)-propionique optiquement actif et resolution optique de ( )-1-methyl-3-phenylpropylamine
US7385080B2 (en) Method for producing optically active β-phenylalanine compounds

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): JP US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB IT LU NL SE

WWE Wipo information: entry into national phase

Ref document number: 1990901867

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1990901867

Country of ref document: EP

WWW Wipo information: withdrawn in national office

Ref document number: 1990901867

Country of ref document: EP

点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载