WO2003005010A2 - Verfahren zur herstellung von optisch aktiven cyanhydrinen - Google Patents
Verfahren zur herstellung von optisch aktiven cyanhydrinen Download PDFInfo
- Publication number
- WO2003005010A2 WO2003005010A2 PCT/EP2002/006681 EP0206681W WO03005010A2 WO 2003005010 A2 WO2003005010 A2 WO 2003005010A2 EP 0206681 W EP0206681 W EP 0206681W WO 03005010 A2 WO03005010 A2 WO 03005010A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- optically active
- aldehyde
- mol
- salen
- catalyst
- Prior art date
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/08—Preparation of carboxylic acids or their salts, halides or anhydrides from nitriles
Definitions
- the invention relates to a process for the production of optically active cyanohydrins by means of an optically active vanadyl catalyst.
- Optically active cyanohydrins and their secondary products e.g. optically active ⁇ -hydroxycarboxylic acids serve as building blocks for the production of biologically active substances, e.g. used in the pharmaceutical or agro industry.
- Cyanohydrins are accessible through various chemical reactions, such as in Top. Curr. Chem. 1999, 200, 193-226.
- a synthesis possibility for optically active cyanohydrins consists in aldehydes in the presence of molecules with "CN" groups (HCN, MCN with M: alkali metal, trimethylsilyl cyanide - also known as TMSCN, cyanohydrins such as acetone cyanohydrin) and an optically active catalyst in (S) - or (R) - to convert cyanohydrins (Compr. Asymmetrie Catal. I-Ill, 1999 (2), Chap. 28).
- Vanadyl salen complexes catalyze the reaction of aldehydes with trimethylsilyl cyanide in principle with higher enantioselectivity than the corresponding titanium salen catalysts (YN Belokon, M. North, T. Parsons, Org. Lett. 2000, 2, 1617-1619.)
- TMSCN TMSCN
- a CN source such as trimethylsilyl cyanide is not very suitable for industrial use because it is expensive and also causes large amounts of silicon-containing waste.
- the implementation of low temperatures such as -80 ° C in technical applications is also expensive and not very practical.
- the present invention solves this problem and relates to a process for the production of optically active cyanohydrins by reacting aldehydes with a CN source in an organic solvent in the presence of an optically active vanadyl catalyst at a temperature in the range from 0 to 60 ° C., wherein the catalyst contains a salen ligand and the catalyst contains 1, 4 to 10 equivalents of salen ligand based on one equivalent of vanadium (IV).
- the invention relates to the preparation of cyanohydrins of the formula (II)
- R represents an optionally branched, alkyl, alkenyl or alkynyl radical of chain length Ci to C 2 o, in particular Ci to Cs, or a radical of the formula (lla)
- X, Y and Z are independently the same or different and represent H, F, CI, Br, I, OH, NH 2 , 0 (dC 4 alkyl), OCOCH 3 , NHCOCH3, N0 2 or CC 4 alkyl ,
- Cyanohydrins of the formula (II) are obtained by reacting an aldehyde of the formula (I)
- aldehydes of the formula (Ia) are used
- X preferably represents F, CI, Br, I, OH, 0 (-CC 4 -alkyl), OCOCH 3 , NHCOCH3, N0 2 or CrC 4 -alkyl and Y and Z each represent H or X and Y each for H and Z for OH or X for H and Y and Z each for OH.
- hydrocyanic acid hydrocyanic acid stabilized with acid or a cyanohydrin, in particular acetone cyanohydrin
- a cyanohydrin in particular acetone cyanohydrin
- the cyanohydrin contained in the reaction mixture can optionally be converted directly into the corresponding ⁇ -hydroxycarboxylic acid by hydrolysis.
- An advantage of the process according to the invention is that it is possible not only to use the aldehydes in comparatively low concentrations, for example 0.1 mol aldehyde / liter, as has been customary hitherto, but also to implement the reaction with considerably higher aldehyde concentrations, for example 2.0 mol aldehyde / liter up to 10 mol aldehyde / liter, preferably 2 to 4 mol aldehyde / liter. Accordingly, the space-time yield for stereoselective cyanohydrin reactions is unusually high.
- the reaction with HCN is carried out in an organic solvent.
- organic solvents or solvent mixtures which are inert under the reaction conditions are suitable for this.
- C O -CIO aromatic and C 1 -C 10 aliphatic, optionally halogenated hydrocarbons or solvent mixtures thereof, and aliphatic ethers having 1 to 5 carbon atoms per alkyl radical, or cyclic ethers having 4 to 5 carbon atoms in the ring are particularly suitable as solvents.
- C ⁇ -Cio preferably C ö -CG-hydrocarbons such as toluene, ortho-, meta- and / or para-xylene, chlorinated aliphatic or aromatic hydrocarbons, such as methylene chloride, dichloroethane, trichloroethane, chloroform, Chlorobenzene, dichlorobenzene and trichlorobenzene, or ethers, such as, for example, diethyl ether, di-n-propyl ether, di-iso-propyl ether, di-n-butyl ether and methyl tert-butyl ether.
- C ⁇ -Cio preferably C ö -CG-hydrocarbons
- chlorinated aliphatic or aromatic hydrocarbons such as methylene chloride, dichloroethane, trichloroethane, chloroform, Chlorobenzene, dichlorobenzene and trichlorobenz
- the inventive process is carried out at a temperature of 0 to 60 ° C. C, preferably 10 to 50 ° C, especially 20 to 40 ° C.
- Suitable catalysts are vanadyl-salen complexes consisting of salen ligands of the general formula (III) and vanadium in the oxidation stage (IV).
- radicals R, R 'and R "of the salen ligand of the general formula (III) can independently of one another be hydrogen, branched or unbranched C 1 -C 10
- Alkyl radicals in particular a methyl or tert-butyl radical, or a group 0 (Cr C -alkyl), in particular a methoxy group or halogens, in particular CI, a substituted aryl group, in particular a phenyl group, or - (CH 2 ) m -. where m can be an integer between 1 and 8.
- the ratio of salen ligand: vanadium (IV) in the catalyst is in the range from 1.4: 1 to 10: 1, preferably in the range from 1.4: 1 to 5: 1, in particular in the range from 1.4: 1 to 3: 1.
- German patent application P (internal number R 4485) described, to which reference is hereby expressly made.
- the catalyst is prepared by reacting vanadyl sulfate with 1.4 to 10, in particular 1.4 to 5 equivalents of the corresponding salen ligand.
- the catalysts contain salen ligands of the formula (III) and vanadium in the oxidation stage (IV) and are preferably synthesized in alcohols in a heterogeneous reaction environment or in a chlorinated hydrocarbon / alcohol mixture in a heterogeneous reaction environment.
- the vanadyl salen catalyst is mixed with the aldehyde and HCN in a suitable solvent.
- 0.00005 to 0.05 equivalents of catalyst preferably 0.0001 to 0.01 equivalents of catalyst, based on the aldehyde, are used.
- the reaction is carried out at 0 to 60 ° C., in particular at 10 to 50 ° C., preferably at 20 to 40 ° C. In many cases it has proven useful to let the reaction proceed at room temperature.
- the aldehyde is added to the reaction mixture in a concentration of 0.1 to 10.0, in particular 0.5 to 5.0, preferably 1.0 to 4.5 mol, of aldehyde. In a large number of cases, it has proven useful to carry out the reaction with HCN with an aldehyde concentration of 2.0 to 4.0 mol / liter.
- the optically active cyanohydrin can be isolated from the reaction mixture and, if necessary, purified.
- the optically active cyanohydrin e.g. crystallize in the cold, preferably at temperatures in the range from -20 ° C to 10 ° C.
- optically active cyanohydrin if appropriate in the form of the reaction mixture, can also be converted, for example by acid hydrolysis, into the corresponding optically active ⁇ -hydroxycarboxylic acid.
- Strong mineral acids such as conc., Are usually used for the acid hydrolysis.
- Sulfuric acid In the hydrolysis is for a thorough mixing of the aqueous Phase in which the acid is contained and the organic phase in which the optically active cyanohydrin is located.
- the rate of the saponification reaction can be increased by adding an ether (for example diisopropyl ether) or a phase transfer catalyst (for example a polyethylene glycol).
- the process according to the invention surprisingly makes it possible to convert aldehydes with high conversions and good ee values into the optically active cyanohydrins of both the (S) and the (R) series.
- particularly difficult substrates such as benzaldehydes substituted in the 2-position, for example 2-chlorobenzaldehyde, can be successfully converted to the corresponding optically active (S) - or (R) -cyanohydrins using the process according to the invention.
- a complex is prepared in the examples below from salen ligands of the formula (III) and vanadium in the oxidation stage (IV), such as, for. B. Vanadyl (IV) sulfate is used.
- Example 12 Analogously to Example 12, 0.15 mol of 4-fluorobenzaldehyde, 2,4-difluorobenzaldehyde and 2,6-difluorobenzaldehyde are reacted with the VO salen complex from Example 1.
- Example 14 2,4-difluorobenzaldehyde reacts to (S) -2,4-difluorobenzaldehyde cyanohydrin with 94% conversion and 79% ee.
- Example 15 2,4-difluorobenzaldehyde reacts to (S) -2,4-difluorobenzaldehyde cyanohydrin with 94% conversion and 79% ee.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Catalysts (AREA)
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP02753068A EP1404645A2 (de) | 2001-06-30 | 2002-06-18 | Verfahren zur herstellung von optisch aktiven zyanhydrinen |
JP2003510935A JP2004533490A (ja) | 2001-06-30 | 2002-06-18 | 光学活性シアノヒドリンおよびそれらの対応する酸の製造法 |
US10/482,246 US20040171862A1 (en) | 2001-06-30 | 2002-06-18 | Method for producing optically active cyanohydrins and their corresponding acids |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10131810.3 | 2001-06-30 | ||
DE10131810A DE10131810A1 (de) | 2001-06-30 | 2001-06-30 | Verfahren zur Herstellung von optisch aktiven Cyanhydrinen und deren korrespondierenden Säuren |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2003005010A2 true WO2003005010A2 (de) | 2003-01-16 |
WO2003005010A3 WO2003005010A3 (de) | 2003-09-25 |
Family
ID=7690192
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2002/006681 WO2003005010A2 (de) | 2001-06-30 | 2002-06-18 | Verfahren zur herstellung von optisch aktiven cyanhydrinen |
Country Status (5)
Country | Link |
---|---|
US (1) | US20040171862A1 (de) |
EP (1) | EP1404645A2 (de) |
JP (1) | JP2004533490A (de) |
DE (1) | DE10131810A1 (de) |
WO (1) | WO2003005010A2 (de) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9682913B2 (en) | 2013-03-29 | 2017-06-20 | Kowa Company, Ltd. | Method for improving optical purity of 2-hydroxycarboxylic acid or derivative thereof |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE10131811A1 (de) * | 2001-06-30 | 2003-04-03 | Clariant Gmbh | Optisch aktive Katalysatoren |
CN100398507C (zh) * | 2005-06-21 | 2008-07-02 | 四川省天然气化工研究院 | Dl-扁桃酸的制备方法 |
WO2007013555A1 (ja) | 2005-07-28 | 2007-02-01 | Kowa Co., Ltd. | 光学活性2-ヒドロキシ酪酸エステルの製造法 |
CN101376679B (zh) * | 2007-08-31 | 2010-09-22 | 中国石油化工股份有限公司 | 负载型钒系非茂聚烯烃催化剂及制备方法与应用 |
JP5353046B2 (ja) | 2008-04-18 | 2013-11-27 | 住友化学株式会社 | 光学活性なシアノヒドリン化合物の製造方法 |
CN113336636B (zh) * | 2021-05-25 | 2023-11-10 | 湖州柏特生物科技有限公司 | 一种高收率的dl-扁桃酸的合成工艺 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002010095A2 (en) * | 2000-08-02 | 2002-02-07 | King's College London, An Institution Incorporated By Royal Charter | Process for the cyanation of aldehydes |
WO2002066410A1 (en) * | 2001-02-16 | 2002-08-29 | Avecia Limited | Preparation of mandelic acid derivatives |
WO2003004157A2 (de) * | 2001-06-30 | 2003-01-16 | Clariant Gmbh | Optisch aktive katalysatoren enthaltend einen salenliganden und vanadium (iv), ihre herstellung und ihre verwendung zur herstellung von cyanhydrinen |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1464605A (en) * | 1973-08-14 | 1977-02-16 | Nippon Sheet Glass Co Ltd | Humidity-sensitive sensor |
US5348761A (en) * | 1989-08-29 | 1994-09-20 | E + E Elektronik Gesellschaft M.B.H. | Use of a swellable plastic and process for making a resistive moisture sensor |
JP3291982B2 (ja) * | 1995-06-21 | 2002-06-17 | 松下電器産業株式会社 | 結露センサおよびそれを用いた電子機器 |
DE19732109A1 (de) * | 1997-07-25 | 1999-01-28 | Clariant Gmbh | Mischungen von optischen Aufhellern |
JP2002142792A (ja) * | 2000-11-01 | 2002-05-21 | Clariant Gmbh | 光学活性シアノヒドリンおよび二次生成物の製造法 |
-
2001
- 2001-06-30 DE DE10131810A patent/DE10131810A1/de not_active Withdrawn
-
2002
- 2002-06-18 WO PCT/EP2002/006681 patent/WO2003005010A2/de not_active Application Discontinuation
- 2002-06-18 JP JP2003510935A patent/JP2004533490A/ja active Pending
- 2002-06-18 US US10/482,246 patent/US20040171862A1/en not_active Abandoned
- 2002-06-18 EP EP02753068A patent/EP1404645A2/de not_active Withdrawn
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002010095A2 (en) * | 2000-08-02 | 2002-02-07 | King's College London, An Institution Incorporated By Royal Charter | Process for the cyanation of aldehydes |
WO2002066410A1 (en) * | 2001-02-16 | 2002-08-29 | Avecia Limited | Preparation of mandelic acid derivatives |
WO2003004157A2 (de) * | 2001-06-30 | 2003-01-16 | Clariant Gmbh | Optisch aktive katalysatoren enthaltend einen salenliganden und vanadium (iv), ihre herstellung und ihre verwendung zur herstellung von cyanhydrinen |
Non-Patent Citations (2)
Title |
---|
BELOKON Y N ET AL: "Mechanistic Investigation of the Asymmetric Addition of Trimethylsilyl Cyanide to Aldehydes Catalysed by Dinuclear Chiral (Salen)titanium Complexes" EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, WILEY-VCH VERLAG, WEINHEIM, DE, Nr. 14, 7. September 2000 (2000-09-07), Seiten 2655-2661, XP002224270 ISSN: 1434-193X in der Anmeldung erw{hnt * |
BELOKON Y.N. ET AL.: "Vanadium-Catalyzed Asymmetric Cyanohydrin Synthesis" ORGANIC LETTERS, Bd. 2, Nr. 11, 2000, Seiten 1617-1619, XP002238262 in der Anmeldung erw{hnt * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9682913B2 (en) | 2013-03-29 | 2017-06-20 | Kowa Company, Ltd. | Method for improving optical purity of 2-hydroxycarboxylic acid or derivative thereof |
Also Published As
Publication number | Publication date |
---|---|
US20040171862A1 (en) | 2004-09-02 |
JP2004533490A (ja) | 2004-11-04 |
EP1404645A2 (de) | 2004-04-07 |
DE10131810A1 (de) | 2003-02-27 |
WO2003005010A3 (de) | 2003-09-25 |
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