EP1511565A2 - Catalyseur et procede de cyanation d'aldehydes - Google Patents

Catalyseur et procede de cyanation d'aldehydes

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Publication number
EP1511565A2
EP1511565A2 EP03730328A EP03730328A EP1511565A2 EP 1511565 A2 EP1511565 A2 EP 1511565A2 EP 03730328 A EP03730328 A EP 03730328A EP 03730328 A EP03730328 A EP 03730328A EP 1511565 A2 EP1511565 A2 EP 1511565A2
Authority
EP
European Patent Office
Prior art keywords
optionally substituted
catalyst
groups
ring
aldehyde
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.)
Ceased
Application number
EP03730328A
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German (de)
English (en)
Inventor
Michael North
Yuri Belokon
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.)
Kings College London
AN Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences INEOS RAS
Original Assignee
Kings College London
AN Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences INEOS RAS
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Filing date
Publication date
Application filed by Kings College London, AN Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences INEOS RAS filed Critical Kings College London
Publication of EP1511565A2 publication Critical patent/EP1511565A2/fr
Ceased legal-status Critical Current

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/22—Organic complexes
    • B01J31/2204—Organic complexes the ligands containing oxygen or sulfur as complexing atoms
    • B01J31/2208—Oxygen, e.g. acetylacetonates
    • B01J31/2226—Anionic ligands, i.e. the overall ligand carries at least one formal negative charge
    • B01J31/2243—At least one oxygen and one nitrogen atom present as complexing atoms in an at least bidentate or bridging ligand
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
    • B01J31/1805—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing nitrogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C253/00—Preparation of carboxylic acid nitriles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/30—Addition reactions at carbon centres, i.e. to either C-C or C-X multiple bonds
    • B01J2231/34—Other additions, e.g. Monsanto-type carbonylations, addition to 1,2-C=X or 1,2-C-X triplebonds, additions to 1,4-C=C-C=X or 1,4-C=-C-X triple bonds with X, e.g. O, S, NH/N
    • B01J2231/341—1,2-additions, e.g. aldol or Knoevenagel condensations
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
    • B01J2531/0238—Complexes comprising multidentate ligands, i.e. more than 2 ionic or coordinative bonds from the central metal to the ligand, the latter having at least two donor atoms, e.g. N, O, S, P
    • B01J2531/0241—Rigid ligands, e.g. extended sp2-carbon frameworks or geminal di- or trisubstitution
    • B01J2531/0252—Salen ligands or analogues, e.g. derived from ethylenediamine and salicylaldehyde
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/50—Complexes comprising metals of Group V (VA or VB) as the central metal
    • B01J2531/56—Vanadium

Definitions

  • This invention relates to a catalyst, a process for the preparation of said catalyst and a process for the cyanation of aldehydes, particularly to the asymmetric cyanation of aldehydes, including the synthesis of chiral cyanohydrins and derivatives thereof, such as chiral O-acyl cyanohydrins.
  • the synthesis of chiral intermediates such as chiral cyanohydrins and derivatives is an important process for use in the manufacture of fine chemicals, agrochemicals and pharmaceuticals.
  • Enantiomerically pure cyanohydrins and derivatives are known to be versatile intermediates for the synthesis of a wide range of commercially important compounds.
  • chiral cyanohydrins and derivatives are intermediates for the synthesis of: ⁇ -hydroxy-acids, ⁇ -amino alcohols, and 1 ,2-diols.
  • chiral cyanohydrins are themselves components of highly successful pyrethroid insecticides.
  • PCT/GB01/03455 discloses a new process for the cyanation of aldehydes, and is particularly directed at the asymmetric cyanation of aldehydes.
  • the asymmetric cyanation of aldehydes is a highly useful synthetic procedure for the synthesis of chiral cyanohydrins and derivatives thereof, such as chiral O-acyl cyanohydrins. There is therefore a need for new catalysts for use in asymmetric cyanation of aldehydes.
  • R 1 and R 2 are independently hydrogen, halogen, cyano, nitro, hydroxy, amino, thiol, an optionally substituted hydrocarbyl, perhalogenated hydrocarbyl, an optionally substituted heterocyclyl, an optionally substituted hydrocarbyloxy, an optionally substituted mono or di-hydrocarbylamino, an optionally substituted hydrocarbylthio, an optionally substituted acyl, an optionally substituted ester, an optionally substituted carbonate, an optionally substituted amide, or an optionally substituted sulphonyl or sulphonamido group, or comprise part of a fused ring;
  • R 3 and R 4 are independently halogen, cyano, nitro, hydroxy, amino, thiol, an optionally substituted hydrocarbyl, perhalogenated hydrocarbyl, an optionally substituted heterocyclyl, an optionally substituted hydrocarbyloxy, an optionally substituted mono or di-hydrocarbylamino, an optionally substituted hydrocarbylthio, an optionally substituted acyl, an optionally substituted ester, an optionally substituted carbonate, an optionally substituted amide, or an optionally substituted sulphonyl or sulphonamido group, or R 3 & R 4 optionally being linked in such a way as to form an optionally substituted ring(s);
  • Y is a neutral ligand
  • X is an anion
  • Hydrocarbyl groups which may be represented by R _1-4 independently include alkyl, alkenyl and aryl groups, and any combination thereof, such as aralkyl and alkaryl, for example benzyl groups
  • Alkyl groups which may be represented by R 1"4 include linear and branched alkyl groups comprising up to 20 carbon atoms, particularly from 1 to 7 carbon atoms and preferably from 1 to 5 carbon atoms. When the alkyl groups are branched, the groups often comprise up to 10 branched chain carbon atoms, preferably up to 4 branched chain atoms. In certain embodiments, the alkyl group may be cyclic, commonly comprising from 3 to 10 carbon atoms in the largest ring and optionally featuring one or more bridging rings.
  • alkyl groups which may be represented by R 1"4 include methyl, ethyl, propyl, 2-propyl, butyl, 2-butyl, t-butyl, t-pentyl, cyclohexyl and adamantyl groups.
  • Alkenyl groups which may be represented by R 1"4 include C 2-20 , and preferably C 2-6 alkenyl groups. One or more carbon - carbon double bonds may be present.
  • the alkenyl group may carry one or more substituents, particularly phenyl substituents. Examples of alkenyl groups include vinyl, styryl and indenyl groups.
  • Aryl groups which may be represented by R 1"4 may contain 1 ring or 2 or more fused rings which may include cycloalkyl, aryl or heterocyclic rings.
  • aryl groups which may be represented by R 1"4 include phenyl, tolyl, fluorophenyl, chlorophenyl, bromophenyl, trifluoromethylphenyl, anisyl, naphthyl and ferrocenyl groups.
  • Perhalogenated hydrocarbyl groups which may be represented by R 1"4 include perhalogenated alkyl and aryl groups, and any combination thereof, such as aralkyl and alkaryl groups.
  • Examples of perhalogenated alkyl groups which may be represented by R 1"4 include -CF 3 and -C 2 F 5 .
  • Heterocyclic groups which may be represented by R 1"4 include aromatic, saturated and partially unsaturated ring systems and may constitute 1 ring or 2 or more fused rings which may include cycloalkyl, aryl or heterocyclic rings.
  • the heterocyclic group will contain at least one heterocyclic ring, the largest of which will commonly comprise from 3 to 7 ring atoms in which at least one atom is carbon and at least one atom is any of N, O, S or P.
  • Examples of heterocyclic groups which may be represented by R 1"4 include pyridyl, pyrimidyl, pyrrolyl, thienyl, furanyl, indolyl, quinolyl, isoquinolyl, imidazoyl and triazoyl groups.
  • R 3 & R 4 are linked in such a way as to form an optionally substituted ring(s), the largest ring commonly comprises from 5 to 7 ring atoms.
  • R 1"4 is a substituted hydrocarbyl, heterocyclic group, hydrocarbyloxy, mono or di-hydrocarbylamino, hydrocarbylthio, acyl, ester, carbonate, amide, sulphonyl or sulphonamido group, or R 3 & R 4 are linked in such a way as to form a substituted ring(s) the substituent(s) should be such so as not to adversely affect the reaction.
  • Optional substituents include halogen, cyano, nitro, hydroxy, amino, thiol, acyl, hydrocarbyl, perhalogenated hydrocarbyl, heterocyclyl, hydrocarbyloxy, mono or di-hydrocarbylamino, hydrocarbylthio, esters, carbonates, amides, sulphonyl and sulphonamido groups wherein the hydrocarbyl groups are as defined above for R 1"4 .
  • One or more substituents may be present.
  • Neutral ligands which may be represented by Y include water, C 1-4 alcohols, C 1-4 thiols, C ⁇ -8 ethers, C 1-8 thioethers, C* ⁇ -8 primary, secondary or tertiary amines, and aromatic amines for example pyridine.
  • a preferred basic ligand represented by Y is water.
  • Anions which may be represented by X include, halide, sulphate, alkylsulphate, perchlorate, PF 6 " , acetate, tosylate and triflate.
  • R 1 or R 2 are independently alkyl groups, preferably methyl, ethyl, propyl, 2-propyl, butyl, 2-butyl, t-butyl, t-pentyl and cyclohexyl groups.
  • R 1 and R 2 are independently 2-propyl, butyl, 2-butyl, t-butyl, t- pentyl and cyclohexyl groups. Most preferably R 1 and R 2 are independently t-butyl, t-pentyl and cyclohexyl groups.
  • R 3 and R 4 are independently halogen, cyano, nitro, an optionally substituted hydrocarbyl, perhalogenated hydrocarbyl, an optionally substituted heterocyclyl, an optionally substituted hydrocarbyloxy, an optionally substituted di- hydrocarbylamino, an optionally substituted hydrocarbylthio, an optionally substituted acyl, an optionally substituted ester, an optionally substituted carbonate, an optionally substituted amide, or an optionally substituted sulphonyl or sulphonamido group, or R 3 & R 4 optionally being linked in such a way as to form an optionally substituted ring(s) More preferably R 3 and R 4 are independently alkyl or aryl groups, or R 3 & R 4 are linked in such a way as to form an optionally substituted ring comprising from 5 to 7 ring atoms, the ring atoms being carbon atoms.
  • R 3 and R 4 are independently alkyl or aryl groups, the alkyl or aryl groups are methyl or phenyl groups. More preferably when R 3 & R 4 are linked in such a way as to form an optionally substituted ring, the ring comprises 6 ring atoms and the ring atoms are preferably carbon atoms.
  • R 3 & R 4 are linked in such a way as to form an un-substituted ring comprising 6 ring atoms and the ring atoms are carbon atoms.
  • Preferred catalysts are those in which R 1 and R 2 are independently 2-butyl, t-butyl, t-pentyl and cyclohexyl groups, and R 3 and R 4 are independently methyl or phenyl groups, or R 3 & R 4 are linked in such a way as to form an optionally substituted ring comprising 6 ring atoms, the ring atoms being carbon atoms.
  • More preferred catalysts are those in which R 1 and R 2 are independently 2-butyl, t- butyl, t-pentyl and cyclohexyl groups, and R 3 and R 4 are independently methyl or phenyl groups, or R 3 & R 4 are linked in such a way as to form an optionally substituted ring comprising 6 ring atoms, the ring atoms being carbon atoms
  • catalysts are those in which R 1 and R 2 are independently 2-butyl, t- butyl, and t-pentyl groups, and R 3 & R 4 are linked in such a way as to form an optionally substituted ring comprising 6 ring atoms, the ring atoms being carbon atoms
  • Catalysts according to the present invention have been found to be useful in processes for the cyanation of aldehydes.
  • the chiral catalyst of formula (3a) or (3b) is as described above in connection with the first aspect of the present invention.
  • Aldehydes which can be employed in the process of the present invention have the chemical formula R 5 -CHO, wherein R 5 is a substituted or unsubstituted hydrocarbyl group, including perhalogenated hydrocarbyl groups.
  • Hydrocarbyl groups which may be represented by R 5 include alkyl, alkenyl, aryl and heterocyclic groups, and any combination thereof, such as aralkyl and alkaryl, for example benzyl groups.
  • Alkyl groups which may be represented by R 5 include linear and branched alkyl groups comprising up to 20 carbon atoms, particularly from 1 to 7 carbon atoms and preferably from 1 to 5 carbon atoms. When the alkyl groups are branched, the groups often comprise up to 10 branched chain carbon atoms, preferably up to 4 branched chain atoms. In certain embodiments, the alkyl group may be cyclic, commonly comprising from 3 to 10 carbon atoms in the largest ring and optionally featuring one or more bridging rings. Examples of alkyl groups which may be represented by R 5 include methyl, ethyl, propyl, 2-propyl, butyl, 2-butyl, t-butyl and cyclohexyl groups.
  • Alkenyl groups which may be represented by R 5 include C 2-20 , and preferably C 2-6 alkenyl groups. One or more carbon - carbon double bonds may be present.
  • the alkenyl group may carry one or more substituents, particularly phenyl substituents. Examples of alkenyl groups include vinyl, styryl and indenyl groups.
  • Aryl groups which may be represented by R 5 may contain 1 ring or 2 or more fused rings which may include cycloalkyl, aryl or heterocyclic rings.
  • aryl groups which may be represented by R 5 include phenyl, tolyl, fluorophenyl, chlorophenyl, bromophenyl, trifluoromethylphenyl, anisyl, naphthyl and ferrocenyl groups.
  • Perhalogenated hydrocarbyl groups which may be represented by R 5 include perhalogenated alkyl and aryl groups, and any combination thereof, such as aralkyl and alkaryl groups.
  • Examples of perhalogenated alkyl groups which may be represented by R 5 include -CF 3 and -C 2 F 5 .
  • Heterocyclic groups which may be represented by R 5 include aromatic, saturated and partially unsaturated ring systems and may constitute 1 ring or 2 or more fused rings which may include cycloalkyl, aryl or heterocyclic rings.
  • the heterocyclic group will contain at least one heterocyclic ring, the largest of which will commonly comprise from 3 to 7 ring atoms in which at least one atom is carbon and at least one atom is any of N, O, S or P.
  • Examples of heterocyclic groups which may be represented by R 5 include pyridyl, pyrimidyl, pyrrolyl, thienyl, furanyl, indolyl, quinolyl, isoquinolyl, imidazoyl and triazoyl groups.
  • R 5 is a substituted hydrocarbyl or heterocyclic group
  • the substituent(s) should be such so as not to adversely affect the reaction.
  • Optional substituents include halogen, cyano, nitro, hydroxy, amino, thiol, acyl, hydrocarbyl, perhalogenated hydrocarbyl, heterocyclyl, hydrocarbyloxy, mono or di-hydrocarbylamino, hydrocarbylthio, esters, carbonates, amides, sulphonyl and sulphonamido groups wherein the hydrocarbyl groups are as defined for R 5 above.
  • One or more substituents may be present.
  • the cyanide source is an inorganic cyanide, preferably a metal cyanide or an in situ source of inorganic cyanide such as acetone cyanohydrin.
  • Particularly preferred cyanide sources comprise alkali metal and alkaline earth metal cyanides, for example, lithium, sodium, potassium, rubidium, caesium, magnesium and calcium cyanides.
  • the most preferred cyanide source is potassium cyanide.
  • the reaction between the aldehyde and the cyanide source occurs in the presence of a substrate susceptible to nucleophilic attack which does not comprise a halogen leaving group.
  • substrates are compounds having the general formula Q-Y, wherein Q represents an organic acid radical, and Y represents a non- halogen leaving group.
  • the leaving group, Y is a leaving group the conjugate acid of which has a pKa of greater than about -2, such as greater than 3, and often less than 12.
  • leaving groups include alkyl and aryl sulphonates, such as mesylate and tosylate; carbonates; especially alkyl carbonates; carboxylates, especially alkyl carboxylates; and groups of formula -NR x R y , wherein R x and R y together with the nitrogen atom form an unsaturated heterocyclic ring which may comprise one or more additional heteroatoms, especially nitrogen, particularly imidazole or benzimidazole rings.
  • alkyl and aryl sulphonates such as mesylate and tosylate
  • carbonates especially alkyl carbonates
  • carboxylates especially alkyl carboxylates
  • groups of formula -NR x R y wherein R x and R y together with the nitrogen atom form an unsaturated heterocyclic ring which may comprise one or more additional heteroatoms, especially nitrogen, particularly imidazole or benzimidazole rings.
  • X represents O, S, N-R or NOR wherein R represents H or a substituted or unsubstituted hydrocarbyl group as defined for R 5 above;
  • the substrate susceptible to nucleophilic attack which does not comprise a halogen leaving group is a carboxylic acid anhydride or an anhydride of a carbonic acid.
  • Carboxylic anhydrides include mixed anhydrides and are often the anhydrides of C 1-8 alkyl or aryl carboxylic acids, such as acetic anhydride and trifluoroacetic anhydride.
  • Carbonic acid anhydrides include di-tert-butyldicarbonate, (tBuOCOOCOOtBu), N,N'-disuccinyldicarbonate, N,N'-dimaleimyldicarbonate, N-(tert- butyl-oxycarbonyloxy) maleimide or succinimide, and N-(benzyloxycarbonyloxy) maleimide or succinimide.
  • the process according to the present invention is commonly carried out in the presence of a solvent.
  • Preferred solvents are polar, aprotic solvents, including halocarbons, for example dichloromethane, chloroform and 1 ,2-dichloroethane; nitriles, for example acetonitrile; ketones, for example acetone and methylethylketone; ethers, for example diethylether and tetrahydrofuran; and amides, for example dimethylformamide, dimethylacetamide and N-methylpyrolidinone.
  • halocarbons for example dichloromethane, chloroform and 1 ,2-dichloroethane
  • nitriles for example acetonitrile
  • ketones for example acetone and methylethylketone
  • ethers for example diethylether and tetrahydrofuran
  • amides for example dimethylformamide, dimethylacetamide and N-methylpyrolidinone.
  • the process of the present invention is carried out in the presence of an additive which accelerates the rate of reaction.
  • additives are inorganic bases such as Na 2 CO 3 , K 2 CO 3 or CaCO 3 or comprise a nucleophilic heteroatom, and often have pKa of greater than 10, for example in the range from 15-35, such as from 15-25.
  • preferred additives include organic bases, such as pyridine, 2,6-lutidine and imidazole; alcohols, such as C ⁇ -6 alcohols, especially tertiary alcohols such as t-butanol; and water.
  • the reaction mixture will be heterogeneous. In such circumstances, it is therefore desirable to employ efficient agitation of the reaction mixture.
  • Agitation means known in the art for example mechanical stirrers and ultrasonic agitators, selected appropriately according to the scale of reaction can be employed as desired.
  • the process of the present invention is often carried out a temperature of from about -40°C to about 40°C. Lower temperatures may be employed if desired, although they are not believed to be advantageous. Commonly, the reaction is carried out a temperature of from -25°C to ambient temperature, such as 15-25°C.
  • the use of the catalysts of the first aspect of the present invention in these processes may facilitate the reactions being carried out at temperatures which are higher than those which can be employed with other catalysts (particularly Ti(lV) catalysts) and still exhibit a high degree of enantio-selectivity.
  • the product of the cyanation reaction in the presence of the substrate susceptible to nucleophilic attack which does not comprise a halogen leaving group can then be reacted, for example by hydrolysis, to form a cyanohydrin.
  • the substrate susceptible to nucleophilic attack which does not comprise a halogen leaving group has the general formula Q-Y, the process can be represented by the sequence:
  • the process according to the present invention is particularly suited to the enantioslective cyanation of aldehydes. It has been found that particularly effective enantioselective cyanation of aldehydes can be achieved by employing an order of addition in which a mixture of chiral catalyst, cyanide source, solvent and aldehyde are prepared, preferably an additive as described above is added to this mixture. The temperature of this mixture is then adjusted to the desired reaction temperature if necessary, and the substrate susceptible to nucleophilic attack not comprising a halogen leaving group is added. This approach has been found to be especially suited when the additive comprises lutidine, t-butanol or water and the substrate susceptible to nucleophilic attack not comprising a halogen leaving group is a carboxylic anhydride.
  • Certain embodiments of the present invention comprise the use of a heterogeneous mixture of an alkali metal cyanide, or alkaline earth metal cyanide (or other inexpensive cyanide sources such as acetone cyanohydrin), an additive (which may be a base e.g. pyridine; or water) and acetic anhydride (or other carboxylic acid anhydrides) to generate a cyanating agent for aldehydes.
  • an additive which may be a base e.g. pyridine; or water
  • acetic anhydride or other carboxylic acid anhydrides
  • R 8 alkyl, aryl, aralkyl, and may contain halogen, oxygen, nitrogen, or sulfur atoms within the group.
  • R 9 alkyl, aryl, aralkyl, and may contain halogen, oxygen, nitrogen, or sulfur atoms within the group.
  • M alkali metal or alkaline earth metal.
  • This invention allows the synthesis of chiral cyanohydrin derivatives derived from a wide variety of aldehydes.
  • the products can be transformed into other chiral compounds by standard chemistry using either of the acyl or nitrile functional groups.
  • a process for the cyanation of an aldehyde group which comprises reacting the aldehyde with: i) an alkali metal cyanide; and ii) a carboxylic anhydride; in the presence of a catalyst of formula (3a) or (3b).
  • the chiral catalyst of formula (3a) or (3b) is as described above in connection with the first aspect of the present invention.
  • a process for the preparation of an O-acyl cyanohydrin which comprises reacting an aldehyde with potassium cyanide and a carboxylic anhydride in the presence of a catalyst of formula (3a) or (3b).
  • the chiral catalyst of formula (3a) or (3b) is as described above in connection with the first aspect of the present invention.
  • the chiral transition metal catalyst and a metal cyanide can be added as mixture.
  • a mixture is believed to be a novel composition of matter, and accordingly forms another aspect of the present invention.
  • Preferred transition metal catalysts and metal cyanides are as described above with respect to the first aspect of the present invention.
  • Catalysts according to the present invention may be prepared by reaction of a suitable compound of vanadium with a ligand in the presence of oxygen. Typically vanadyl sulphate hydrate is reacted with a salen ligand in solvent in the presence of oxygen.
  • Optical rotations were recorded on an Optical Activity Ltd. Polar 2001 or a Perkin-Elmer 241 polarimeter, and are reported along with the solvent and concentration in g/100 mL.
  • Elemental analyses were performed on a Carlo Erba Model 1106 or Model 1108 analyser.
  • Chiral GC was carried out on a DP-TFA- ⁇ -CD, fused silica capillary column (32m x 0.2 mm) using helium as the carrier gas.
  • Dichloromethane was distilled over CaH 2 .
  • Acetic anhydride was distilled from the commercial product (99%).
  • Commercial potassium cyanide (98%) was thoroughly powdered and stored in vacuo over P 2 O 5 .
  • Aliphatic and aromatic aldehydes were purified by usual methods.
  • Chiral ligands were prepared by refluxing 1 ,2-cyclohexyldiamines (R,R and S,S) with 2,4- di-fer.-butyl salicylaldehyde.
  • reaction mixture was vigorously stirred for 10 hours at the same temperature. Solid salts were then filtered and washed thoroughly with dichloromethane. To remove the catalyst the reaction mixture was filtered through a pad of silica (10 mm x 50 mm) eluting with dichloromethane. The solvent was evaporated.//? vacuo, and the resulting light green residue fractionated in vacuo giving the benzaldehyde cyanohydrin acetate. B.p. 95-97°C (0.2 mm); yield 7.5 g (87.2%); ee (S), 90.3%.

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  • Engineering & Computer Science (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
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Abstract

L'invention concerne un catalyseur au vanadium et un procédé de cyanation d'un aldéhyde. Ce catalyseur de vanadium comprend un complexe de salen de vanadium (V). Ce procédé consiste à faire réagir de l'aldéhyde avec: i) une source de cyanide qui ne comprend pas de liaison Si-CN ou un fragment C-(C=O)-CN; et ii) un substrat sensible à l'attaque nucléophile qui ne comprend pas d'halogène de groupe partant; en présence d'un catalyseur de vanadium chiral. La source de cyanide est de préférence un cyanide métallique alcalin et le substrat sensible à l'attaque nucléophile et qui ne comprend pas de groupe partant halogène est un anhydride carboxylique.
EP03730328A 2002-05-24 2003-05-22 Catalyseur et procede de cyanation d'aldehydes Ceased EP1511565A2 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GBGB0212017.8A GB0212017D0 (en) 2002-05-24 2002-05-24 Catalyst and process
GB0212017 2002-05-24
PCT/GB2003/002227 WO2003099435A2 (fr) 2002-05-24 2003-05-22 Catalyseur et procede de cyanation d'aldehydes

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EP1511565A2 true EP1511565A2 (fr) 2005-03-09

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EP (1) EP1511565A2 (fr)
JP (1) JP2005526608A (fr)
KR (1) KR20050013551A (fr)
AU (1) AU2003241010A1 (fr)
CA (1) CA2487295A1 (fr)
GB (1) GB0212017D0 (fr)
MX (1) MXPA04011593A (fr)
WO (1) WO2003099435A2 (fr)

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GB0603120D0 (en) * 2006-02-16 2006-03-29 Npil Pharmaceuticals Uk Ltd Process for the cyanation of imines
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GB0212017D0 (en) 2002-07-03
AU2003241010A1 (en) 2003-12-12
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