Organic compounds -- part of the class 532-570 series – Organic compounds – Nitriles
Reexamination Certificate
2001-02-27
2001-09-11
McKane, Joseph K. (Department: 1626)
Organic compounds -- part of the class 532-570 series
Organic compounds
Nitriles
Reexamination Certificate
active
06288264
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to a process for preparing cyanoacetamide by esterification without additional catalyst. During this esterification crude cyanoacetic acid is reacted with a monohydric alcohol which forms an azeotrope with water. The resulting ester is reacted with ammonia in the presence of a basic catalyst to give cyanoacetamide, followed by work-up using a mechanical separating operation and thermal treatment.
2. Discussion of the Background
Cyanoacetamide is an important intermediate for preparing drugs and pharmaceutical products. It is used inter alia for preparing malononitrile.
Syntheses of cyanoacetamide from cyanoacetic esters are known from the literature. For example, Organic Synthesis Collect., Volume 1, pg. 179 describes a process in which ethyl cyanoacetate is reacted with concentrated aqueous ammonia. This results in wastewater which is polluted with organic products and which must be disposed of. Moreover, it is necessary to work up the mother liquor to achieve a good yield. Processes of this type are complicated and not economic.
European Patent Application EP-A-0 583 694 describes the use of butanol in a large excess of 5 to 30 times the molar amount of cyanoacetic acid and a strongly acidic catalyst for the esterification. The esterification times are very long despite the catalyst. (For example, a reaction time of 13 hours is disclosed in the Examples of EP-A-0 583 694.
SUMMARY OF THE INVENTION
It is an object of the present invention to develop a process for preparing cyanoacetamide which is technically simple to implement, for example, in an industrial process, with short reaction times and with little complexity. It is another object of the present invention to develop a process for preparing cyanoacetamide, that does not yield waste which is complicated and costly to dispose of.
These and other objects have been achieved according to the invention, the first embodiment of which includes a process for preparing cyanoacetamide from cyanoacetic acid and ammonia, comprising:
(1) optionally, azeotropically distilling out water from cyanoacetic acid with a first monohydric alcohol having 4 to 10 carbon atoms;
(2) esterifying said cyanoacetic acid with a second monohydric alcohol without additional catalyst;
distilling out the water/alcohol mixture, thereby providing a crude ester;
(3) optionally purifying said crude ester by distillation out from high boilers, thereby providing a purified ester;
(4) reacting said crude ester or said purified ester with ammonia in the presence of a basic catalyst, thereby providing crude cyanoacetamide; and
(5) working up the crude cyanaoacetamide by a mechanical separating operation and thermal treatment.
DETAILED DESCRIPTION OF THE INVENTION
The object of the present invention is achieved by esterifying a low-cost crude cyanoacetic acid with an unbranched or branched monohydric alcohol having 4 to 10, preferably 4 to 6, carbon atoms without additional catalysts. The resulting ester is further reacted in crude or after only the higher boiling fractions have been removed by distillation. This resulting ester is preferably reacted with gaseous ammonia in the presence of a basic catalyst to give cyanoacetamide.
The work-up takes place by a mechanical separating operation such as filtration or separation in a hydrocyclone, and a thermal treatment such as vacuum-drying.
Surprisingly, it has been found that the synthetic route via the esters, preferably via the butyl esters, provides the following considerable advantages:
the esters can be prepared without an additional catalyst,
the work-up of the ester is omitted,
direct conversion to the amide is possible,
with the exception of monohydric alcohol, the mother liquor produced in the amide preparation is free of valuable product, or
additional concentration of the mother liquor can be omitted during repeated crystallization. Thus, the process according to the invention for preparing cyanoacetamide is particularly simple and economic.
The invention therefore relates to a process for preparing cyanoacetamide from crude cyanoacetic acid, which optionally contains water. The process includes the following steps:
(1) Azeotropic distillation with unbranched or branched monohydric alcohols with 4 to 10 carbon atoms to remove the water dissolved in the starting material, where appropriate.
(2) Azeotropic water/alcohol distillation in the esterification of the crude cyanoacetic acid with monohydric alcohols, wherein the esterification is free of additional catalyst.
(3) Optionally, initial purification of the ester by distilling the ester off from high boilers.
(4) Reaction of the ester with ammonia in the presence of a basic catalyst, where appropriate in a monohydric alcohol having 4 to 10 carbon atoms.
(5) Work-up by a mechanical separating operation and a thermal treatment.
The process according to the invention requires no additional solvents either in the first two or in the third stage. It has the advantage that only very small amounts of auxiliaries are required and the monohydric alcohol which is employed in excess can be recovered by simple distillation of high boiling fractions and can be recycled. The preferred monohydric alcohol is butanol.
The molar ratio of alcohol to cyanoacetic acid is 1:1 to 4:1, preferably 1.5:1 to 2.5:1. The molar ratio includes all values and subvalues therebetween, especially including 1.6:1; 1.7:1; 1.8:1; 1.9:1; 2.0:1; 2.1:1; 2.2:1; 2.3:1 and 2.4:1. This ratio determines the bottom temperature under atmospheric pressure, which is preferably not above 140° C. because of the low stability of the acid. For this reason, it is preferable to operate under vacuum conditions. The temperature for the esterification is preferably 100 to 140° C. The temperature includes all values and subvalues therebetween, especially including 105, 110, 115, 120, 125, 130 and 135° C.
Preferred suitable monohydric alcohols are unbranched or branched alcohols which form an azeotrope with water and have 4 to 10, and more preferably 4 to 6 carbon atoms. Butanols are particularly preferred, especially n-butanol and i-butanol.
The catalysts used for reacting the ester with ammonia are compounds which are basic or have a basic action. Preferred catalysts are alkali metal alcoholates or alkaline earth metal alcoholates such as sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, magnesium methoxide and magnesium ethoxide. These catalysts can be used singly or as mixtures. The catalysts are used in very small amounts of from 0.5 to 10 mol %, preferably 1 to 5 mol % and more preferably 1 to 2.5 mol % of catalyst, based on the amount of acid originally employed.
The ammonia is preferably used in a stoichiometric amount and preferably in the gaseous state. The temperature for reacting the ester with ammonia is 10 to 100° C., preferably 20 to 80° C. The temperature includes all values and subvalues therebetween, especially including 20, 30, 40, 50, 60, 70, 80 and 90° C.
The cyanoacetamide can be purified by recrystallization (see Org. Synthesis Coll. Volume 1, page 179 et seq.). Depending on the required quality, particularly with regard to the color of the cyanoacetamide, it is preferred to prepurify the crude ester before the amide preparation.
The distillation apparatus is preferably a short-path apparatus, and more preferably a short-path evaporator.
Having generally described this invention, a further understanding can be obtained by references to certain specific examples which are provided herein for purposes of illustration only, and are not intended to be limiting unless otherwise specified.
REFERENCES:
patent: 0 583 694 A1 (1994-02-01), None
H. Gilman, et al. (eds.), Organic Synthesis Collective vol. 1, pp. 178-181, (1972).
Imig Manuela
Kalz Thomas
Kaufhold Manfred
Degussa-Huels Aktiengesellschaft
McKane Joseph K.
Murray Joseph
Oblon & Spivak, McClelland, Maier & Neustadt P.C.
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