Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acids and salts thereof
Reexamination Certificate
2000-01-14
2002-05-28
Geist, Gary (Department: 1623)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acids and salts thereof
C560S190000
Reexamination Certificate
active
06395931
ABSTRACT:
This application is the national phase under 35 U.S.C. § 371 of PCT International Application No. PCT/BH98/00058 which has an International filing date of Aug. 10, 1998, which designated the United States of America.
FIELD OF THE INVENTION
The present invention relates to a process for preparing malonic acid and its esters from cyanoacetic acid which is hydrolyzed in the presence of aqueous hydrochloric acid. More specifically, the present invention relates to a high-yield process for obtaining malonic acid as well as its respective esters in C
1
-C
10
from cyanoacetic acid, specially to the esters derived from secondary alcohols, such as isopropyl alcohol.
BACKGROUND INFORMATION
Malonic acid and specially its esters are widely used industrial products which find application mainly in the fields of pharmaceuticals, agricultural products and cosmetics.
Malonic acid production from the hydrolysis of cyanoacetic acid in the presence of strong acids such as sulfuric acid or bases is well-known.
Alternatively, malonic acid esters may be prepared from the acid hydrolysis of cyanoacetic acid in the presence of the alcohol which will generate the desired ester.
Esters of malonic acid may also be obtained from the classical route which involves the esterification of pure malonic acid.
Another well-known process utilizes the carbonylation of chloracetic acid in the presence of alcohols in order to prepare the esters of malonic acid.
Japanese patents JP 51-143612 A, JP 59-007135, JP 59-007136 A and U.S. Pat. No. 2,337,858 teach that malonic acid esters may be prepared from procedures which involve high consumption of sulfuric acid, the synthesis of malonic acid per se being not reported.
The process taught in
ORGANIC SYNTHESES COLLECTION—VOLUME II
, A. H. BLATT Ed., JOHN WILEY, New York, 1943, page 376 is based on the alkaline hydrolysis of cyanoacetic acid so as to obtain the salt of malonic acid which then is made to react with calcium chloride in order to form calcium malonate. This salt is made into the free salt by means of acid hydrolysis and then extracted with an organic solvent.
Japanese patent 53-127411 teaches the preparation of malonic acid through the alkaline hydrolysis of cyanoacetamide with calcium hydroxide and then acidification with sulfuric acid.
However, the open literature does not present processes leading to a high-yield hydrolysis of cyanoacetic acid as well as the application of such hydrolysis to ester derivatives of secondary alcohols from the mixture of malonic acid contaminated with hydrolysis by-products such as ammonium salts, such process being described and claimed in the present application.
SUMMARY OF THE INVENTION
The process for preparing malonic acid and its esters according to the present invention comprises:
Preparation of the Concentrated Mixture
Malonic acid is prepared through the hydrolysis of cyanoacetic acid in the presence of an at least stoichiometric amount of aqueous hydrochloric acid yielding a mixture which is the desired product malonic acid and the by-product ammonium chloride besides small amounts of acetic acid. A concentrated mixture is obtained when malonic acid and ammonium chloride are separated from water, acetic acid and the excess hydrochloric acid present in the medium;
Isolation of Malonic Acid
The concentrated mixture of malonic acid and ammonium chloride is purified by dissolving with an oxygen organic solvent the malonic acid product being then separated from the ammonium chloride by-product so as to obtain malonic acid purified and isolated through evaporation of the oxygen organic solvent;
Preparation of Malonic Esters
The concentrated mixture of malonic acid and ammonium chloride is purified by dissolving with the esterifying alcohol, the malonic acid-esterifying alcohol mixture being separated from the ammonium chloride by-product and esterified in the presence of a Brönsted acid catalyst and an azeotrope-forming organic co-solvent, under heating, in order to obtain the desired ester product.
Therefore, the present process for preparing malonic acid comprises the hydrolysis of cyanoacetic acid in the presence of an at least stoichiometric amount of aqueous hydrochloric acid in a concentration between 5 and 37% by weight, yielding a mixture which is the desired product malonic acid and by-product ammonium chloride, which should be separated from water, excess hydrochloric acid and acetic acid by-product in order to obtain a concentrated mixture which is purified by dissolving with an oxygen organic solvent under suitable conditions of pressure and temperature, the desired product being then separated from the ammonium chloride by-product so as to obtain malonic acid which is purified and isolated by evaporating the oxygen organic solvent.
And the process for preparing the malonic esters according to the present invention comprises the hydrolysis of cyanoacetic acid in the presence of an at least stoichiometric amount of aqueous hydrochloric acid in a concentration in the range of 5 to 37% by weight, yielding a mixture which is the desired product malonic acid and by-product ammonium chloride, which should be separated from water, excess hydrochloric acid and acetic acid by-product in order to obtain a concentrated mixture, such mixture being purified by dissolving with the esterifying alcohol, the mixture malonic acid-esterifying alcohol being separated from the ammonium chloride by-product and esterified in the presence of a Brönsted acid catalyst and a ternary azeotrope-forming organic solvent, under heating, so as to obtain the desired ester product.
Thus, the present invention provides a process for preparing malonic acid and its esters in high yields as a consequence of the hydrolysis under mild conditions in the presence of aqueous hydrochloric acid, such conditions reducing the decarboxylation of the desired product, therefore lowering the amount of acetic acid by-product of the reaction.
The present invention provides further a process for preparing malonic acid of low water content and low concentration in residual mineral acid as a consequence of the use of volatile hydrochloric acid. The volatile hydrochloric acid may be recovered on evaporating, then concentrated and recycled to the process. The relatively low concentration of hydrolyzing agent as well as the low temperature in the medium during evaporation leads to high yields.
Still, the present invention provides a process for preparing malonic acid esters in high yield as a consequence of running the esterification in the presence of catalytic amounts of a Brönsted acid, so as to minimize the decarboxylation besides the dehydration of alcohol, particularly secondary alcohols.
REFERENCES:
patent: 2337858 (1943-12-01), Stoesser
patent: 2459144 (1949-01-01), Christie
patent: 953874 (1956-12-01), None
patent: 1240410 (1969-11-01), None
patent: 51143612 (1976-12-01), None
patent: 53127411 (1978-11-01), None
patent: A-597135 (1984-01-01), None
patent: A-597136 (1984-01-01), None
patent: 6613168 (1968-03-01), None
M. L. Henry, “Sur le dinitrile malonique”, Compte Rendus, vol. 102, (1886), pp. 1394-1397.*
Kiyoshi Matsumoto et al, “Reaction of Pyridinium Bis(methoxycarbony)methylid with Diphenylcyclopropenethione: A Revised Structure for One of the Products” Heterocyles, vol. 23(8), (1985), pp. 2041-2043).*
“On the Conversion of Cyanacetic Ester to Malonic Ester” Phelps et al. Chemical Abstracts 3, p. 1533 (1909).*
Derwent Publication Ltd., London, GB; AN 84-046207 XP-002089183.
Derwent Publication Ltd., London, GB: AN 84-046206 XP-002089184.
Organic Syntheses, Collective vol. 2, Revised Edition of Annual vol. X-XIX Edited by A.H. Blatt; Taken from Reg. No. 09/971,211; Published by John Wile & Sons; pp. 376-378.
Aguiar Sandro da Silva
Carvalho Otavio Vianna
de Castro Antonio Luiz Ribeiro
Fujiyama Jane Hitoni
Mansur Ronaldo Mendonca
Birch & Stewart Kolasch & Birch, LLP
Geist Gary
Trikem S.A.
Tucker Zachary C.
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