CA2297636C - Process for preparing cyanoacetic esters - Google Patents

Abstract

Cyanoacetic esters of the general formula:

Description

Process For Preparing Cyanoacetic Esters The present invention relates to a process for preparing cyanoacetic esters of the general formula:

I-IR (I) in which R is Cl_lo-aikyl, C3_10-alkenyl or aryl-C1_9-alkyl.
C1_lo-alkyl is to be understood as any linear or branched primary, secondary or tertiary alkyl group having 1 to 10 carbon atoms, in particular groups such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl or decyl.
C3_10-alkenyl is to be understood as the corresponding groups having 3 to 10 carbon atoms and at least one C=C double bond, where the double bond is advantageously separated from the free valency by at least one saturated carbon atom. These include, in particular, groups such as allyl, methallyl, but-2-enyl (crotyl), but-3-enyl, etc.
Aryl-C1_4-alkyl is to be understood as, in particular, phenyl-substituted C1_q-alkyl groups such as, for example, benzyl, phenethyl or 3-phenylpropyl, where the phenyl group may also carry one or more identical or different substituents such as, for example, C1_q-alkyl, C1_4-alkoxy or halogen.
Conventionally, the synthesis of cyanoacetic esters is carried out by cyanidation of sodium chloroacetate in aqueous solution, followed by an acid-catalysed esterification with the appropriate alcohol, where the water formed is distilled off azeotropically. An essential disadvantage of this two-step process is the fact that the water has to be removed after cyanidation, since the subsequent esterification is only possible under substantially water-free conditions. On an industrial scale, this is usually carried out by evaporating the water.

Since the sodium cyanoacetate which is formed as an intermediate is moreover highly water-soluble, a method for its esterification in water as the solvent is desirable.

Accordingly, it is an object of the present invention to develop a process where the aqueous solution of sodium cyanoacetate which is obtained after cyanidation can be esterified directly.

According to the invention, it has been found that cyanoacetic esters of the general formula:
~
~_"~ R (I) in which R is Cl_lo-alkyl or C3-1o-alkenyl can be prepared by reacting sodium cyanoacetate in the form of the aqueous solution obtained in the reaction of sodium chloroacetate with sodium cyanide in an aqueous/organic two-phase system in the presence of a phase-transfer catalyst with a halide of the general formula R-X(II), in which R is as defined above and X is chlorine, bromine or iodine. The organic phase used can be the halide (II) on its own or in a mixture with an organic solvent.

The alkali metal cyanoacetate which is preferably used is sodium cyanoacetate.

Sodium cyanoacetate is particularly preferably employed in the form of an aqueous solution obtained by the reaction of sodium chloroacetate with sodium cyanide.

X is preferably chlorine or bromine.

The phase-transfer catalyst which is preferably employed is a quaternary ammonium salt. Particularly preferred quaternary ammonium salts are the tetra-n-Ca_1o-alkylammonium, benzyltri-n-C1_e-alkylammonium or methyltri-n-C4_10-alkylammonium halides, in particular the chlorides and bromides.

Preference is also given to using tert-butyl methyl ether or chlorobenzene as solvent in the organic phase.
The following Examples illustrate the manner in which the process according to the present invention may be carried out, without limiting it. All reactions were carried out in an autoclave having an internal volume of about 250 ml.
The yield was determined by gas chromatography with the aid of an internal standard.

Example 1 Methyl cyanoacetate 10.0 g (9.9 equivalents, 0.20 mol) of methyl chloride were introduced into 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 tert-butyl methyl ether/water 2:1. The reaction mixture was heated to an internal temperature of 100 C (oil bath temperature 110 C) over a period of 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 vented.
The pH of the aqueous phase was adjusted from 2.9 to 5.9 using 3.10 g of 1 M aqueous sodium hydroxide solution, the organic phase was separated off and the aqueous phase was extracted with tert-butyl methyl ether (2x6 ml). The combined organic phases were dried with sodium sulfate, admixed with dimethyl succinate (as internal standard) and analysed by gas chromatography. 1.36 g(680) of methyl cyanoacetate was obtained.
Comparative Example 1 Methyl cyanoacetate The method described in Example 1 was repeated, but without the addition of tetrabutylammonium bromide. The yield of methyl cyanoacetate was only 13%.

Example 2 Ethyl cyanoacetate A mixture of 1.70 g (0.02 mol) of cyanoacetic acid, 0.8 g(0.02 mol) of sodium hydroxide, 10.90 g(0.10 mol, 5 equivalents) of ethyl bromide and 0.64 g(2.0 mmol) of tetrabutylammonium bromide in 15 ml of chlorobenzene/water (2:1) was heated to an internal temperature of 100 C over a period of 30 minutes and stirred at 100 C (oil bath temperature 110 C) for 3.5 hours. The reaction mixture was then cooled, the phases were separated and the aqueous phase (pH = 6.85) was extracted with tert-butyl methyl ether (2x5 ml). The combined organic phases were dried with sodium sulfate, admixed with dimethyl succinate (as internal standard) and analysed by gas chromatography. 1.46 g (65%) of ethyl cyanoacetate was obtained.

Example 3 Benzyl cyanoacetate A mixture of 1.7 g(0.02 mol) of cyanoacetic acid, 0.8 g (0.02 mol) of sodium hydroxide, 7.60 g (0.06 mol, 3 equivalents) of benzyl chloride and 0.64 g (2.0 mmol) of tetrabutylammonium bromide in 15 ml of tert-butyl methyl ether/water (v:v = 2:1) was stirred at 100 C (oil bath temperature 110 C) for 3 hours. 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 solutiori, the organic phase was separated off and the aqueous phase was extracted with tert-butyl methyl ether (2x5 ml). The combined organic phases were dried with sodium sulfate and analysed by gas chromatography. 2.45 g (70%) of benzyl cyanoacetate was obtained.

Claims (6)

1. A process for preparing cyanoacetic esters of the general formula in which R is C1-10-alkyl or C3-10-alkenyl, wherein sodium cyanoacetate in the form of the aqueous solution obtained in the reaction of sodium chloroacetate with sodium cyanide is reacted in an aqueous/organic two-phase system in the presence of a phase-transfer catalyst with a halide of the general formula R-X(II), in which R is as defined above and X is chlorine, bromine or iodine.

2. The process according to Claim 1, wherein X is chlorine or bromine.

3. The process according to Claim 1 or 2, wherein the phase-transfer catalyst used is a quaternary ammonium salt.

4. The process according to Claim 3, wherein the quaternary ammonium salt used is a tetra-n-C4-10-alkyl ammonium, benzyltri-n-C1-8-alkyl ammonium or methyltri-n-C4-10-alkyl ammonium halide.

5. The process according to Claim 4, wherein the alkyl ammonium halide is a chloride or bromide.

6. The process according to any one of Claims 1 to 5, wherein the organic phase comprises tert-butyl methyl ether or chlorobenzene as solvent.