Synthesis of esters of mercaptocarboxylic acids

Details Synthesis of esters of mercaptocarboxylic acids Synthesis of esters of mercaptocarboxylic acids

2000-05-08

2001-11-06

Barts, Samuel (Department: 1621)

Organic compounds -- part of the class 532-570 series

Organic compounds

Carboxylic acid esters

Reexamination Certificate

active

06313342

ABSTRACT:

The present invention relates to the preparation of esters of mercaptocarboxylic acids and more particularly to the synthesis of esters of the general formula:
HS—X—COOR  (I)
in which X denotes a linear or branched alkylene radical containing from 1 to 4 carbon atoms and R a linear or branched alkyl radical containing from 1 to 18 carbon atoms, preferably 1 to 12.
BACKGROUND OF THE INVENTION
These known esters are used industrially as intermediate products, especially for the manufacture of tin derivatives which are useful as heat stabilizers for polyvinyl chloride and, in the case of the lower alcohol esters (especially R=methyl), for the manufacture of heterocyclic (thiophene or thiazole) derivatives which are useful as plant-protection agents.
The main route for obtaining esters (I) is the esterification of an alcohol ROH with an acid HS—X—COOH, the latter being obtained by the action of a hydrosulphide on the corresponding chloro- or bromocarboxylic acid. Despite its excellent overall yield, this method has the disadvantage of generating a considerable quantity of aqueous saline waste.
It is known that esters of mercaptocarboxylic acids can also be prepared by the action of an alkali metal hydrosulphide on an ester of a halocarboxylic acid. This method has been employed especially by R. M. Acheson et al. (J. Chem. Soc. 1961, pp. 650-660, in particular p. 656) for preparing methyl &agr;-mercapto-&agr;-methylpropionate by the action of sodium hydrosulphide on methyl &agr;-bromo-&agr;-methylpropionate in anhydrous methanol; the yield is very low (approximately 36%). Additional systems are described in Patent Applications JP 48-86818, 63-10755 and 2-304061, both of which operate in the presence of water, either in a hydroalcoholic medium (JP 48-86818 and 63-10755) or in a water-toluene medium in the presence of a phase transfer agent (JP 2-304061).
It has now been found that the presence, in the reaction medium, of appreciable quantities of water (other than that possibly originating from the in-situ formation of the hydrosulphide) is unfavorable for the selectivity of the reaction and that this selectivity is moreover improved by operating at a high pressure of hydrogen sulphide.
SUMMARY OF THE INVENTION
An object of this invention is therefore to provide one or more improved processes for the preparation of the esters of formula (I) by the action of ammonium hydrosulphide or of an alkali or alkaline-earth metal hydrosulphide on the corresponding halocarboxylic ester of formula:
Y—X—COOR  (II)
in which R and X have the same meanings as above and Y denotes a chlorine or bromine atom.
Upon further study of the specification and appended claims, further objects and advantages of this invention will become apparent to those skilled in the art.
To obtain these objects, the reaction is performed under a hydrogen sulphide pressure of at least 10 bars absolute, and preferably in an anhydrous or substantially anhydrous alcoholic medium.
The expression “substantially anhydrous” means here that the reaction medium does not contain water in amounts other than that which may originate from the possible in-situ formation of hydrosulphide, as is the case, for example, with the formation of sodium hydrosulphide according to the reaction:
NaOH+H
2
S →NaSH+H
2
O
A C
1
-C
4
lower alcohol may be employed as alcohol, but it is preferred to work in isopropanol and especially in methanol. Although it is preferred to employ an anhydrous or substantially anhydrous alcoholic medium, the benefits of such a medium are still obtained to a finite extent even though the water content of the medium is as high as 36 g per liter of alcohol used to form the medium.
The reaction may be performed at a temperature ranging from 0 to 80° C., but it is preferred to operate at a temperature of between 10 and 60° C.
The hydrogen sulphide pressure may range up to preferably not more than 30 bars absolute, but is advantageously between 10 and 20 bars absolute. The use of such hydrogen sulphide pressures contribute to improved selectivities, even in media which are not anhydrous or substantially anhydrous.
Although the process according to the invention also applies to bromocarboxylic esters, it is preferred to start from chlorocarboxylic esters, obtained in excellent yields (approximately 96%) according to the esterification reaction:
Cl—X—COOH+ROH→C
1
—X—COOR+H
2
O
Depending on the nature of the ester (II) used, its initial concentration in the reaction medium may preferably range from 1 to 5 moles per liter of alcohol.
An alkali or alkaline-earth metal hydrosulphide such as, for example, NaSH, RSH and Ca(SH)
2
may be employed as the hydrosulphide, but it is preferred to employ ammonium hydrosulphide, which can be formed in situ without producing water. The hydrosulphide/ester (II) molar ratio is generally between 1 and 2 but, in order to obtain a complete conversion of the ester (II), it preferably ranges from 1.1 to 1.5. The values indicated for this ratio should obviously be halved when a difunctional hydrosulphide such as Ca(SH)
2
is employed.
The process according to the invention may be used continuously or discontinuously (batchwise). When compared with the usual process of preparation of esters of mercaptocarboxylic acids by esterification of an alcohol ROH with an acid HS—X—COOH, it offers the advantage, on the one hand, of forming as a by-product approximately half as much ammonium salt or alkali or alkaline-earth metal salt, and on the other hand, of considerably reducing the quantity of saline aqueous waste. In fact, after neutralization of the excess hydrosulphide in the reaction mixture with an acid (preferably HCl or H
2
SO
4
), the precipitated salts can be easily separated off by filtration, before or after evaporation of the alcohol.
Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. The following preferred specific embodiments, are, therefore, to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever.
In the foregoing and in the following examples, all temperatures are set forth uncorrected in degrees Celsius and unless otherwise indicated, all parts and percentages are by weight, and the pressures of H
2
O in bars absolute.
The entire disclosures of all applications, patents and publications, cited above and below, and of corresponding French Application No. P 94/10145, are hereby incorporated by reference.


REFERENCES:
patent: 2262686 (1941-11-01), Kyrides et al.
patent: 3927085 (1975-12-01), Zengel et al.
patent: 5773641 (1998-06-01), Labat et al.
R.M. Acheson et al., “The Synthesis of Some Thiophens Related to . . . ”,J.C.S., pp. 650-660, 1961.
Translation Of Chemical Abstract, JP 63-10755, published Jan. 18, 1988.
Translation of Chemical Abstract, Abstract No. 59499z, vol. 80(11), JP-48-86818, published Nov. 15, 1973.
Acheson et al.. “The Synthesis of Some Thioplens Related to Vitamin A”, J.C.S. 1161 (pp. 650-660), 1961.
Translation of JP 48-86818. 1973.
Translation of JP 63-10755. 1988.

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