• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    Cyanoacetic esters having formula (1) are prepared by reacting an alkali metal cyanoacetate and the corresponding halide of formula (2) in an aqueous phase / organic two-phase system in the presence of a phase-transfer catalyst: Wherein R is C 1-10 -alkyl, C 3-10 -alkenyl or aryl-C 1-4 -alkyl, R-X Wherein X is chlorine, bromine or iodine.
    公开号:KR20000057793A
    申请号:KR1020000003077
    申请日:2000-01-22
    公开日:2000-09-25
    发明作者:힐트브란트슈테판；한젤만파울
    申请人:토마스 케플러, 자비네 루츠；론자 아게；
    IPC主号:
    专利说明:

    Method for preparing cyanoacetic ester {PROCESS FOR PREPARING CYANOACETIC ESTERS}
    The present invention relates to a process for the preparation of cyanoacetic esters having the general formula (1):
    [Formula 1]

    Wherein R is C 1-10 -alkyl, C 3-10 -alkenyl or aryl-C 1-4 -alkyl.
    In the following, C 1-10 -alkyl is any linear or branched primary, secondary or tertiary alkyl group having 1 to 10 carbon atoms, especially methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, It is to be understood that the alkyl group is tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl or decyl.
    C 3-10 -alkenyl is to be understood as a corresponding group having 3 to 10 carbon atoms and at least one C═C double bond, wherein the double bond is advantageously separated from the free valence by one or more saturated carbon atoms . These include in particular allyl, metalyl, 2-butenyl (crotyl), 3-butenyl and the like.
    Aryl -C 1-4 - alkyl, particularly such as benzyl, phenethyl or phenyl substituted with C 1-4, such as 3-phenylpropyl-, to be understood as an alkyl group wherein a phenyl group may also for example C 1-4 - alkyl, C 1 It may have one or more same or different substituents, such as -4 -alkoxy or halogen.
    A conventional method for cyanoacetic ester synthesis is to cyanate sodium acetate in aqueous solution, followed by acid-catalyzed esterification with an appropriate alcohol, and the resulting water is removed by azeotropic distillation. An indispensable drawback of this two step process is that the subsequent esterification is only possible under conditions that are virtually free of water, so that water must be removed after the cyanation process. On an industrial scale it is usually done by evaporating water.
    Since sodium cyanoacetate produced as an intermediate is more water-soluble, the method of esterifying in water as a solvent is preferable.
    Therefore, it was an object of the present invention to develop a method capable of directly esterifying an aqueous solution of sodium cyanoacetate obtained after cyanation.
    According to the invention, this object is achieved by the method of claim 1.
    It has been found that cyanoacetic esters having the following formula (1) can be prepared by reacting an alkali metal cyanoacetate with an halide of formula (2) in an aqueous phase / organic two-phase system in the presence of a phase-transfer catalyst:
    [Formula 1]
    Wherein R is C 1-10 -alkyl, C 3-10 -alkenyl or aryl-C 1-4 -alkyl,
    [Formula 2]
    R-X
    (Wherein R is as defined above and X is chlorine, bromine or iodine).
    The organic phase used may be in the halide (2) itself or in a mixture with an organic solvent.
    Alkali metal cyanoacetate used preferably is sodium cyanoacetate.
    Sodium cyanoacetate is particularly preferably used in the form of an aqueous solution obtained by reacting sodium chloroacetate with sodium cyanide.
    X is preferably chlorine or bromine.
    Phase-transfer catalysts which are preferably used are quaternary ammonium salts. Particularly preferred quaternary ammonium salts are tetra-nC 4-10 -alkylammonium, benzyltri-nC 1-8 -alkylammonium or methyltri-nC 4-10 -alkylammonium halides, in particular chloride and bromide.
    Preference is also given to using tertiary butyl methyl ether or chlorobenzene as solvents in the organic phase.
    The following examples illustrate without limitation the implementation of the method according to the invention. All reactions were carried out in an autoclave with an internal volume of about 250 ml. Yield was determined by gas chromatography using internal standards.
    Example 1
    Methyl cyanoacetate
    10.0 g of methyl chloride in a mixture of 1.70 g (0.02 mol) of cyanoacetic acid, 0.8 g (0.2 mol) of sodium hydroxide and 0.64 g (2.0 mmol) of tetrabutylammonium bromide in 15 ml of tertiary butyl methyl ether / water 2: 1 (9.9 equiv, 0.20 mol) was added. The reaction mixture was heated to an internal temperature of 100 ° C. (oil bath temperature 110 ° C.) for 30 minutes during which the pressure in the autoclave increased from 4 to 10 bar. After 3.5 hours at 100 ° C., the autoclave was cooled and the steam was vented. Using 3.10 g of 1 M aqueous sodium hydroxide solution, the pH of the aqueous phase was adjusted from 2.9 to 5.9, the organic phase was separated and the aqueous phase was extracted with tertiary butyl methyl ether (2 x 6 ml). The combined organic phases were dried over sodium sulfate, dimethyl succinate (as internal standard) was mixed and analyzed by gas chromatography. Methyl cyanoacetate 1.36 g (68%) was obtained.
    Comparative Example 1
    Methyl cyanoacetate
    Without addition of tetrabutylammonium bromide, the method described in Example 1 was repeated. The yield of methyl cyanoacetate was only 13%.
    Example 2
    Ethyl cyanoacetate
    1.70 g (0.02 mol) cyanoacetic acid, 0.8 g (0.02 mol) sodium hydroxide, 10.90 g (0.10 mol, 5 equiv) ethyl bromide and 0.64 g tetrabutylammonium bromide in 15 ml of chlorobenzene / water (2: 1) 2.0 mmol) was heated to an internal temperature of 100 ° C. for 30 minutes and stirred at 100 ° C. for 3.5 hours (oil bath temperature 110 ° C.). The reaction mixture was then cooled, the phases were separated and the aqueous phase (pH = 6.85) was extracted with tertiary butyl methyl ether (2 x 5 ml). The combined organic phases were dried over sodium sulphate, mixed with dimethyl succinate (as internal standard) and analyzed by gas chromatography. Ethyl cyanoacetate 1.46 g (65%) was obtained.
    Example 3
    Benzyl Cyanoacetate
    1.7 g (0.02 mol) cyanoacetic acid, 0.8 g (0.02 mol) sodium hydroxide, 7.60 g (0.06 mol, 3 equiv) in 15 ml tertiary butyl methyl ether / water (v: v = 2: 1) and A mixture of 0.64 g (2.0 mmol) of tetrabutylammonium bromide was stirred at 100 ° C. for 3 hours (oil bath temperature 110 ° C.). The pH of the aqueous phase was then adjusted from 0.2 to 6.3 using 3.15 g of 1 M aqueous sodium hydroxide solution, the organic phase was separated off and the aqueous phase was extracted with tertiary butyl methyl ether (2 × 5 ml). The combined organic phases were dried over sodium sulphate and analyzed by gas chromatography. 2.45 g (70%) of benzyl cyanoacetate was obtained.
    As a method for synthesizing cyanoacetic ester of the present invention, the aqueous sodium acetate solution obtained after cyanation can be esterified directly without removing water after the cyanation process, which is a disadvantage of the conventional method.
    权利要求:
    Claims (7)
    [1" claim-type="Currently amended] A process for preparing a cyanoacetic ester of formula (I), characterized in that an alkali metal cyanoacetate is reacted with a halide of formula (II) in an aqueous phase / organic two-phase system in the presence of a phase-transfer catalyst:
    [Formula 1]
    Wherein R is C 1-10 -alkyl, C 3-10 -alkenyl or aryl-C 1-4 -alkyl,
    [Formula 2] R-X
    (Wherein R is as defined above and X is chlorine, bromine or iodine).
    [2" claim-type="Currently amended] The method according to claim 1, wherein the alkali metal cyanoacetate used is sodium cyanoacetate.
    [3" claim-type="Currently amended] The method according to claim 2, wherein sodium cyanoacetate is used in the form of an aqueous solution obtained in the reaction of sodium chloroacetate and sodium cyanide.
    [4" claim-type="Currently amended] 4. A process according to any one of claims 1 to 3 wherein X is chlorine or bromine.
    [5" claim-type="Currently amended] The process according to any one of claims 1 to 4, wherein the phase-transfer catalyst used is a quaternary ammonium salt.
    [6" claim-type="Currently amended] The quaternary ammonium salt to be used is tetra-nC 4-10 -alkylammonium, benzyltri-nC 1-8 -alkylammonium or methyltri-nC 4-10 -alkylammonium halide, preferably chloride And bromide.
    [7" claim-type="Currently amended] 7. Process according to any of the preceding claims, characterized in that the organic phase comprises tertiary butyl methyl ether or chlorobenzene as solvent.
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    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    法律状态:
    1999-02-09|Priority to EP99102286.4
    1999-02-09|Priority to EP99102286
    2000-01-22|Application filed by 토마스 케플러, 자비네 루츠, 론자 아게
    2000-09-25|Publication of KR20000057793A
    2006-07-28|Application granted
    2006-07-28|Publication of KR100606626B1
    优先权:
    申请号 | 申请日 | 专利标题
    EP99102286.4|1999-02-09|
    EP99102286|1999-02-09|
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