EP1404645A2 - Procede pour produire des cyanhydrines optiquement actives et leurs acides correspondants - Google Patents

Procede pour produire des cyanhydrines optiquement actives et leurs acides correspondants

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Publication number
EP1404645A2
EP1404645A2 EP02753068A EP02753068A EP1404645A2 EP 1404645 A2 EP1404645 A2 EP 1404645A2 EP 02753068 A EP02753068 A EP 02753068A EP 02753068 A EP02753068 A EP 02753068A EP 1404645 A2 EP1404645 A2 EP 1404645A2
Authority
EP
European Patent Office
Prior art keywords
optically active
aldehyde
mol
salen
catalyst
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP02753068A
Other languages
German (de)
English (en)
Inventor
Bettina Kirschbaum
Rainer Fell
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Clariant Produkte Deutschland GmbH
Original Assignee
Clariant GmbH
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 Clariant GmbH filed Critical Clariant GmbH
Publication of EP1404645A2 publication Critical patent/EP1404645A2/fr
Withdrawn legal-status Critical Current

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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.

Landscapes

  • 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)
  • Catalysts (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

La présente invention concerne un procédé pour produire des cyanhydrines optiquement actives et les acides α-hydroxycarboxyliques correspondants à partir d'un aldéhyde, d'acide cyanhydrique et d'un catalyseur vanadyle-salen optiquement actif, le mélange réactionnel étant mis en réaction à une température comprise entre 0 et 60 °C. On utilise de préférence 0,8 à 10 équivalents d'acide cyanhydrique et 0,0001 à 0,05 équivalents de catalyseur vanadyle-salen par rapport à l'aldéhyde (concentration 0,5 à 4 mol/litre de solvant). Après la réaction, on peut isoler le cyanhydrine optiquement actif ou, après une hydrolyse acide, l'acide α-hydroxycarboxylique optiquement actif correspondant avec un bon rendement d'énantiomères. Le catalyseur au vanadium utilisé selon l'invention contient un ligand salen, le rapport ligand salen : vanadium-(IV) dans le catalyseur étant compris entre 1,4:1 et 10:1.
EP02753068A 2001-06-30 2002-06-18 Procede pour produire des cyanhydrines optiquement actives et leurs acides correspondants Withdrawn EP1404645A2 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10131810 2001-06-30
DE10131810A DE10131810A1 (de) 2001-06-30 2001-06-30 Verfahren zur Herstellung von optisch aktiven Cyanhydrinen und deren korrespondierenden Säuren
PCT/EP2002/006681 WO2003005010A2 (fr) 2001-06-30 2002-06-18 Procede pour produire des cyanhydrines optiquement actives et leurs acides correspondants

Publications (1)

Publication Number Publication Date
EP1404645A2 true EP1404645A2 (fr) 2004-04-07

Family

ID=7690192

Family Applications (1)

Application Number Title Priority Date Filing Date
EP02753068A Withdrawn EP1404645A2 (fr) 2001-06-30 2002-06-18 Procede pour produire des cyanhydrines optiquement actives et leurs acides correspondants

Country Status (5)

Country Link
US (1) US20040171862A1 (fr)
EP (1) EP1404645A2 (fr)
JP (1) JP2004533490A (fr)
DE (1) DE10131810A1 (fr)
WO (1) WO2003005010A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10131811A1 (de) * 2001-06-30 2003-04-03 Clariant Gmbh Optisch aktive Katalysatoren
JP5094392B2 (ja) 2005-07-28 2012-12-12 興和株式会社 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
EP2980061A4 (fr) 2013-03-29 2016-09-07 Kowa Co Procédé pour améliorer la pureté optique de l'acide 2-hydroxycarboxylique ou de son dérivé
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

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GB1464605A (en) * 1973-08-14 1977-02-16 Nippon Sheet Glass Co Ltd Humidity-sensitive sensor
DE59010077D1 (de) * 1989-08-29 1996-02-29 E & E Elektronik Gmbh Verwendung eines quellfähigen kunststoffes, sowie verfahren zur herstellung eines resistiven feuchtigkeitssensors
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
GB0018973D0 (en) * 2000-08-02 2000-09-20 King S College London Synthesis of chiral cyanohydrins
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
GB0103857D0 (en) * 2001-02-16 2001-04-04 Avecia Ltd Preparation of chloromandelic acid
DE10131811A1 (de) * 2001-06-30 2003-04-03 Clariant Gmbh Optisch aktive Katalysatoren

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Title
See references of WO03005010A2 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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

Also Published As

Publication number Publication date
US20040171862A1 (en) 2004-09-02
WO2003005010A2 (fr) 2003-01-16
JP2004533490A (ja) 2004-11-04
WO2003005010A3 (fr) 2003-09-25
DE10131810A1 (de) 2003-02-27

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