Note: Descriptions are shown in the official language in which they were submitted.
CA 02297636 2000-02-03
Process For Preparing Cyanoacetic Esters
The present invention relates to a process for
preparing cyanoacetic esters of the general formula:
0
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
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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.
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CA 02297636 2000-02-03
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%.
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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.
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