Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
  • C07C209/82—Purification; Separation; Stabilisation; Use of additives
  • C07C209/86—Separation
  • C07C209/88—Separation of optical isomers
• • C—CHEMISTRY; METALLURGY
  • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
  • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
  • C12P13/00—Preparation of nitrogen-containing organic compounds
  • C12P13/02—Amides, e.g. chloramphenicol or polyamides; Imides or polyimides; Urethanes, i.e. compounds comprising N-C=O structural element or polyurethanes
• • C—CHEMISTRY; METALLURGY
  • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
  • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
  • C12P41/00—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture
• • C—CHEMISTRY; METALLURGY
  • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
  • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
  • C12P41/00—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture
  • C12P41/006—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by reactions involving C-N bonds, e.g. nitriles, amides, hydantoins, carbamates, lactames, transamination reactions, or keto group formation from racemic mixtures
  • C12P41/007—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by reactions involving C-N bonds, e.g. nitriles, amides, hydantoins, carbamates, lactames, transamination reactions, or keto group formation from racemic mixtures by reactions involving acyl derivatives of racemic amines

Definitions

• the present invention relates to a new process for the preparation of known, optically active amines which are used as intermediates for the preparation of
• Lipases from Pseudomonas for example Amano P, or from Pseudomonas spec DSM 8246 can be used as hydrolases.
• the optically active, primary and secondary amines can be prepared by first enantio racemic amine in the presence of a hydrolase with an ester which has an electron-rich heteroatom in the acid part in the vicinity of the carbonyl carbon atom - selectively acylated
• R 1 and R 2 are different
• R 1 represents methyl, ethyl or a radical of the formula (II)
• R 3 is a C ⁇ C- Q alkylene radical or a C 2 -C, 0 - AI may learn keny,
• R 4 is a C j -C Q alkyl radical, a C 6 -C 10 aryl radical or a C 7 -C 14 aralkyl radical and
• R 2 represents C - C 10 alkyl or optionally substituted C 6 -C ] 4 aryl
• R 5 and R 6 are the same or different and each represents optionally substituted C - 20 alkyl or optionally substituted C 6 -C] 0 aryl are C and R 5 additionally also be hydrogen,
• R .1 J , R- and R have the meanings given above,
• (R) amines are to be understood as those optically active compounds of the formulas (I) and (IV-R) which have the (R) configuration on the asymmetrically substituted carbon atom.
• (S) amines are those optically active compounds of the To understand formulas (I) and (IS) which have the (S) configuration at the chirate center In the formulas for (R) - and (S) amines, the asymmetrically substituted carbon atom is identified by *.
• Suitable substituents for alkyl and aryl radicals are, for example, up to 3 identical or different substituents from the group comprising C 1 -C 6 -alkyl, C - C 6 -alkoxy, halogen, nitro and cyano radicals substituted with alkyl radicals
• Alkyl residues are branched alkyl residues
• R 1 and R 2 are different from each other, wherein
• R 1 preferably represents methyl, ethyl or a radical of the formula (III) in which R 3 represents a methylene or ethylene radical, R 4 represents a methyl, ethyl,
• Phenyl or benzyl and X are O and
• R 2 preferably represents C r C 4 alkyl
• R 1 very particularly preferably represents -CH 2 -O-CH 3 and R 2 represents methyl
• R 5 preferably represents C 1 -C 6 -alkyl which is optionally substituted once or twice by C 4 -C 4 -alkyl or optionally em 2 to 2 times by C-C 4- alkyl, C ] -C 4 -alkoxy, chlorine, bromine, nitro and / or cyano-substituted phenyl.
• R 5 particularly preferably represents unsubstituted C r C 4 -alkyl.
• R 6 is preferably and independently of R 5 particularly preferably represents one of the radicals set forth in Trains t R 5 as preferred and particularly granted ⁇ most preferably, R 5 is methyl and R 6 is ethyl
• optically active amines of the formula (I-S) can be prepared in high yield and very good optical purity by the process according to the invention on the basis of the known state of the art
• the method according to the invention has a number of advantages. It enables the production of a large number of optically active amines with high yield and excellent optical purity. It is also favorable that it is possible to work with a relatively high substrate concentration, the reaction times are short and continuous operation is possible. It is also advantageous that the required biocatalyst is available in large quantities and is stable even at elevated temperatures. The biocatalyst can be used in a relatively small amount in relation to the substrate. Finally, the implementation of the reaction and the isolation of the desired substances also pose no difficulties.
• racemic amines of the formula (I) required as starting materials for the process according to the invention are known or can be prepared by methods known per se.
• the esters of the formula (III) required are likewise known or can be prepared by methods known per se.
• the required lipase can be used both natively and in immobilized form.
• Immobilizations are, for example, the use of lipase in microencapsulated form or bound to an organic or inorganic carrier material.
• Support materials include, for example, diatomaceous earth, ion exchangers, zeolites, polysaccharides, polyamides and polystyrene resins, in particular Celite ® and Lewatit ® types.
• lipase from Candida antarctica in is suitable
• an ester of the formula (III) Based on one mol of racemic amine of the formula (I), for example 0.5 to 20 mol of an ester of the formula (III) can be used. When working without an additional diluent, this amount of ester is preferably 1 to 10 mol, in particular 1 to 5 mol. When working with the addition of a diluent, this amount of ester is preferably 1 to 7 mol, in particular 1 to 4 mol.
• the process according to the invention can be carried out, for example, at temperatures in the range from 0 to 90 ° C., in particular from 10 to 60 ° C. Usually one works at atmospheric pressure, optionally under an inert gas, for example nitrogen.
• the procedure can be such that the respective racemic amine of the formula (I), the respective ester of the formula (III), if appropriate a diluent and lipase from Candida antarctica are combined in any order and the resulting mixture at the respective reaction temperature until the desired conversion is reached.
• the amount of lipase based on the racemic amine of the formula (I) can be varied within wide limits. For example, 0.1 to 40% by weight of immobilized lipase, eg B use Novozym ® 435, based on the racemic amine of the formula (I), or a corresponding amount of native lipase. This amount is preferably 0.5 to 30% by weight of immobilized lipase or the corresponding amount of native lipase
• (R) -amine of the formula (IV-R) For example, one can at least 0.000001 grams of immobilized lipase, for example Novozym ® 435, per g of racemic amine of the formula (I) or a corresponding amount of native lipase used preferably amounts to this quantity 0 , 00001 to 0.1 g of immobilized lipase or a corresponding amount of native lipase
• the desired (S) -amine of the formula (I-S) can be separated off, for example, by distillation or extraction. Distillation is preferred
• the residue remaining after this separation can be discarded or used in any way.
• the acylated (R) -amine of formula (IV) contained therein can be isolated, for example by distillation, and obtained as such or after its isolation from the acylated (R) -amine of formula (IV) in a manner known per se split off the acyl group and thus obtain the (R) -amine corresponding to the (S) -amine of formula (IS) prepared or racemize the acylated (R) -amine obtained and reuse it in the process according to the invention after removal of the acyl group
• Active ingredients with insecticidal, fungicidal or herbicidal properties are particularly suitable for the preparation of herbicidally active N-thienylchloroacetamides (see, for example, EP-A 296 463 and EP-A 210 320)
• Candida antarctica lipase (Novozym ® 435) filled in suspension in MTBE. The bed volume was 17 ml.
• the immobilized Candida antarctica lipase was separated by filtration from the reaction mixture obtained according to Example 1 and the filtrate was worked up by distillation. At normal pressure, first ethyl acetate, ethanol and MTBE passed over, then at 99 ° C. (S) -2-amino-1-methoxypropane and finally at 13 mbar and 105 to 1 10 ° C (R) -N-acetyl-2-amino-l-methoxypropane
• Example 5 The procedure was as in Example 1, but not fresh immobilized antarctica lipase was used, but rather that which had been recovered according to Example 3. The yield and the ee value for (S) -2-amino-1-methoxypropane were as in Example 1 Example 5

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• Bioinformatics & Cheminformatics (AREA)
• General Engineering & Computer Science (AREA)
• General Health & Medical Sciences (AREA)
• Genetics & Genomics (AREA)
• Analytical Chemistry (AREA)
• Preparation Of Compounds By Using Micro-Organisms (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

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• 1996
  • 1996-02-01 DE DE19603575A patent/DE19603575A1/de not_active Withdrawn
• 1997
  • 1997-01-20 WO PCT/EP1997/000239 patent/WO1997028271A1/de not_active Application Discontinuation
  • 1997-01-20 CA CA002244917A patent/CA2244917A1/en not_active Abandoned
  • 1997-01-20 KR KR1019980705922A patent/KR19990082197A/ko not_active Application Discontinuation
  • 1997-01-20 EP EP97902188A patent/EP0877815A1/de not_active Withdrawn
  • 1997-01-20 JP JP9527273A patent/JP2000504224A/ja active Pending

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