From:
REC. TRAV. CHIM. PAYS-BAS (1940) 59, p. 27
COMPLETE CONVERSION OF l-ECGONINE METHYL ESTER INTO l-COCAINE
by A. W. K. DE JONG
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A complete conversion is obtained in 10 hours by boiling an anhydrous benzene solution of l-ecgonine methyl ester with benzoyl chloride in the presence of dry sodium carbonate, calcium oxide or a mixture of calcium oxide and hydroxide. In chloroform solution about 20 hours are necessary and in ethereal solution about 40 hours, when a mixture of calcium oxide and hydroxide is used.
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[...]
The well-known esterification method of Schotten-Baumann cannot be used since the methyl ester of ecgonine is very easily decomposed by concentrated alkali solution at ordinary temperature.
When Deninger [J.prakt.chem. (1894) 50, 479] stated that benzoic anhydride is formed by heating benzoyl chloride with anhydrous sodium carbonate and a drop of pyridine.
[...]
The presence of water must be avoided since benzoyl chloride as well as l-ecgonine methyl ester are decomposed by boiling them in a solution containing traces of water.
Besides sodium carbonate (obtained by heating fine pulverised sodium carbonate exsiccatus or bicarbonate) calcium oxide and mixtures of calcium oxide with sodium carbonate or calcium hydroxide and the latter admixed with sodium hydroxide, were also used; these last two mixtures were obtained by adding to 25 g of fine pulverised calcium oxide 3.5 ml water or 4 ml 2N sodium hydroxide solution, respectively. As solvent, ether, chloroform and benzene were used. The solutions contained about 1 ml of 0.1N methyl ester in 10 ml.
The experiments were carried out in the following way. To 10 ml of the anhydrous solution 1 g or more of the alkaline compound for absorbing hydrochloric acid and 0.5 ml of benzoyl chloride were added, and the measuring tube washed out with 10 ml of anhydrous solvent. The solution was partly distilled to eliminate possible traces of water and boiled for some hours. The condensor was provided with a calcium chloride tube. The solution was then filtered off and the flask and filter washed three times with anhydrous solvent. It was shaken with about 2 ml 0.1N hydrochloric acid solution + 5 ml water and then twice with 5 ml water. The acid solution was shaken with 25 ml of the solvent to get rid of a trace of benzoyl chloride and the solvent was then shaken twice with 5 ml water. In this way about 27 ml of aqueous solution were obtained.
The excess acid was titrated with methyl red in ether solution as indicator and the quantity of bases present calculated. After saturation with sodium bicarbonate the solution was shaken three times with 15 ml ether. The etheral solution on distillation gave a residue crystallising after inoculation with a trace of cocaine, the quantity being determined by titration.
From the bicarbonate solution unchanged methyl ester can be isolated by shaking nine times with 15 ml of chloroform.
[...]
USING ETHER AS SOLVENT :
(I) = l-ecgonine methyl ester
0.8 ml 0.1N (I) ; 2 g CaO+Ca(OH)2 ; 20 hours : 90% transformed
0.8 ml 0.1N (I) ; 2 g CaO+Ca(OH)2 ; 33 hours : 95% transformed
The transformation is very slow; it takes about 40 hours to complete.
The experiments with chloroform have shown that it is best to dissolve the methyl ester of ecgonine first in benzene and to distill off the solvent from the solution to ensure its being sufficiently anhydrous; [...] The transformation would be complete in about 20 hours.
USING BENZENE AS SOLVENT :
1.25 ml 0.1N (I) ; CaO+Ca(OH)2 ; 7.5 hours : 95% transformed
1.00 ml 0.1N (I) ; calcium oxide ; 10 hours : 100% transformed
0.95 ml 0.1 N (I) ; sodium carbonate ; 10 hours : 100% transformed
Benzene can be obtained sufficiently anhydrous by distilling off until the distillate is no longer cloudy. The conversion is complete in 10 hours.
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