Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acid esters
Reissue Patent
1999-04-12
2001-05-22
Shippen, Michael L. (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acid esters
C564S190000
Reissue Patent
active
RE037188
ABSTRACT:
This invention pertains a process for the preparation of cyclopropanecarboxylic acid by the non-catalytic, oxidation of cyclopropanecarboxaldehyde. This invention also pertains to processes for the preparation of esters and the amide and acid chloride of cyclopropanecarboxylic acid.
Cyclopropanecarboxylic acid and its derivatives, especially cyclopropylamine, are useful in the synthesis of pharmaceuticals and pesticides. See, for example, European Patent Publications EP 237,955 A2, EP 273,862 A2 and EP 430,847 A1. The synthesis of cyclopropanecarboxylic acid by a three-step process consisting of (1) the reaction of a metal cyanide with 1-bromo-3-chloropropane to obtain 4-chlorobutyronitrile, the cyclization of the 4-chlorobutyronitrile to obtain cyclopropanenitrile, and (3) the hydrolysis of the cyclopropanenitrile to obtain cyclopropanecarboxylic acid is disclosed in Japanese Patent Kokai 04077453, Org. Synthesis, Coll. Vol. 1, 156 (1941) and Org. Synthesis, Coll. Vol. 3, 221 (1955). This process requires handling of an extremely toxic metal cyanide and extensive extractions in the isolation of the product. Additional processes for the synthesis of cyclopropanecarboxylic acid on a laboratory scale are described by J. Tu et al., Youji Huaxue 12, pp. 48-50 (1992); J. Yang et al., Huaxue Shijie 31, pp. 356-358 (1990); M. A. Cohen et al., Tetrahedron Letter 31, 7223-7226 (1990); C. W. Jefford et al., J. Chem. Soc. Chem. Commun., pp. 634-635 (1988); S. C. Bunce et al. Org. Prep. Proced. Int., 6, pp. 193-196 (1974); G. M. Lampan et al., J. Chem. Eng. Data. 14, pp. 396-397 (1969). While convenient for laboratory use, the procedures in these cited articles are not suitable for large-scale commercial use due to low yields and/or the use of expensive reagents.
U.S. Pat. No. 3,711,549 discloses the preparation of methyl cyclopropanecarboxylate by the steps of (1) converting &ggr;-butyrolactone to 4-chlorobutyric acid by cleaving &ggr;-butyrolactone in the presence of zinc chloride at 120° C. and 20.7 bars, (2) reacting the 4-chlorobutyric acid with methanol, and (3) cyclizing the methyl 4-chlorobutyrate. The cyclization reaction requires preesterification of the acid since the cyclization condition otherwise would result in conjugative polymerization of the butyric acid moiety or ring closure to reform gamma-butyrolactone. The process of U.S. Pat. No. 3,711,549 requires handling strongly corrosive and hazardous hydrogen chloride in the gaseous state at elevated temperatures and pressures. The process also involves the use of sodium metal in the manufacture of the fresh sodium methoxide needed for the ring closure of 4-chlorobutyrate ester to yield cyclopropanecarboxylate ester. The mentioned requirements of the process described in U.S. Pat. No. 3,711,549 present serious problems with respect to safety in equipment design and material handling.
U.S. Pat. No. 4,590,292 describes a route to cyclopropanecarboxamide from &ggr;-butyrolactone via a four step process. &ggr;-Butyrolactone is cleaved with hydrogen chloride gas in the presence of aqueous sulfuric acid solution to form 4-chlorobutyric acid which is converted into a chlorobutyrate ester. The chlorobutyrate ester is cyclized by sodium hydroxide in the presence of a phase transfer catalyst to yield a cyclopropanecarboxylate ester. This ester is treated with ammonia in the presence of a sodium alkoxide as a catalyst to form cyclopropanecarboxamide. Like the process of U.S. Pat. No. 3,711,549, this process requires the handling of hydrogen chloride gas at elevated temperatures and pressures. To facilitate ring closure of the 4-chlorobutyrate ester to yield the cyclopropanecarboxylate ester, the use of a secondary or tertiary alcohol in the esterification of 4-chlorobutyric acid is essential. Otherwise hydrolysis of the ester becomes a major competitive reaction leading to low yields (U.S. Pat. No. 3,711,549). It is known that esterification using hindered alcohols presents difficulties in driving the reaction to completion. Long reaction times and continuous removal of water (azeotrope with a organic solvent) are required, which leads to higher costs in manufacturing. The cyclization step of this process requires the handling of a chlorinated solvent such as dichloromethane in order to perform the phase transfer-catalyzed cyclization. In the amidation step of the process of U.S. Pat. No. 4,590,292, typically more than 20 mole percent of sodium alkoxide is needed for effective reaction rates. As a result, the isolation of the product from the reaction mixture is difficult and, based on the examples given, the product usually is obtained as a solution of methanol. In the case of the isolation of a pure product, less than a 46% yield is reported. Recycling and repeating the amidation of the mother liquid is required in order to gain higher yields. Since large amounts of catalyst (sodium ethylene glycoxide) are needed, the preparation of the catalyst constitutes an additional step of the process. It is apparent that the process disclosed in U.S. Pat. No. 4,590,292 poses problems with regard to safety and economics.
U.S. Pat. No. 5,068,428 (equivalent of European Patent Specification EP 365,970) discloses a process for the production of cyclopropanecarboxamide by the amidation of isobutyl cyclopropanecarboxylate in the presence of sodium isobutoxide/isobutanol. The isolation of the product from the reaction mixture is not trivial with a moist, salt-containing product usually being obtained. The process has limitations similar to those described in U.S. Pat. No. 4,590,292.
The present invention pertains to the preparation of cyclopropanecarboxylic acid by the non-catalytic, oxidation of cyclopropanecarboxaldehyde which may be obtained by the thermal isomerization or rearrangement of 2,3-dihydrofuran. For example, U.S. Pat. No. 4,275,238 describes passing 2,3-dihydrofuran through a column at 480° C. to obtain cyclopropanecarboxaldehyde having a purity of 90% purity and containing 6.2-6.7% crotonaidehyde. A similar procedure is described by Wilson, J. Amer. Chem. Soc. 69, 3002 (1947). 2,3-Dihydrofuran may be obtained according to the process described in U.S. Pat. No. 5,254,701 by the isomerization of 2,5-dihydrofuran which in turn can be produced by the isomerization of 3,4-epoxy-1-butene as described in U.S. Pat. Nos. 3,932,468, 3,996,248 and 5,082,956. U.S. Pat. Nos. 4,897,498 and 4,950,773 describe the preparation of 3,4-epoxy-1-butene by selective monoepoxidation of butadiene.
The process of the present invention comprises the preparation of cyclopropanecarboxylic acid by contacting cyclopropanecarboxaldehyde with molecular oxygen at elevated temperature. We have discovered that the novel oxidation process proceeds at an acceptable rate in the absence of a catalyst and a solvent which reduces operating costs and greatly simplifies both isolation of the carboxylic acid product and the equipment required for the operation of the process. The rate of oxidation of cyclopropanecarboxaldehyde to cyclopropanecarboxylic acid has been found to be dependent primarily upon oxygen mass transfer rather than any catalyst action. Since the oxidation of an aldehyde to a carboxylic acid is a free radical process [see, for example, Riley et al., J. Org. Chem. 52, 287 (1987)], partial or complete decomposition of the cyclopropane ring was a potential problem of the oxidation process. Another advantage provided by the oxidation process is that it causes the decomposition of crotonaldehyde, an inevitable impurity of cyclopropanecarboxaldehyde obtained from 2,3-dihydrofuran. Since the boiling points of cyclopropanecarboxylic acid and crotonic acid are 182°-184° C. and 180°-181° C., respectively, the conversion of the crotonaldehyde impurity to crotonic acid during the oxidation of cyclopropanecarboxaldehyde to cyclopropanecarboxylic acid would present a very difficult purification problem.
The elevated temperatures which may be employed in the operation of the present oxidation process are in the range of about 10° to 200° C. although temperatures i
Liang Shaowo
Price Timothy W.
Eastman Chemical Company
Shippen Michael L.
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