Benzoyl-Z-ecgonine

When heated with mineral acids Z-cocaine is hydrolysed into Z-ecgonine (p. 96), benzoic acid and methyl alcohol and a like change takes place with baryta water. If the alkaloid is boiled with water, methyl alcohol is split off and a new base, benzoyl-Z-ecgonine is formed, which in turn can be hydrolysed by acids or alkalis into Z-ecgoninc and benzoic acid. Cocaine is, therefore, methylbenzoyl-Z-ecgonine. 

The stepwise hydrolysis is completed by boiling benzoyl-Z-ecgonine with dilute hydrochloric acid. 

Gray (20) has studied the effect of the replacement of the methyl ester of cocaine by other esters on anesthetic activity. The ethyl ester of benzoyl-Z-ecgonine, called cocethyline or methylcocaine, had been made earlier (21, 22) and had been found to possess typical cocaine-like action. 

The by-products in the crude extract from South American coca are removed by oxidation (below 5°) of a solution of the extract in 3% sulfuric acid with saturated permanganate solution. After filtration the base is liberated and crystallized from ether (239). The i-ecgonine, formed by hydrolysis of the esters in the preliminary extraction, may be converted to Z-cocaine by esterification (CHjOH) and benzoylation of the ecgonine methyl ester. A process has been developed whereby cinnamylcocaine and the truxillines are converted to Z-ecgonine methyl ester which in turn is converted by benzoylation to Z-cocaine. 

The recovery of i-cocaine from crude extracts has been increased by hydrolysis of the truxillines and cinnamylcocaine in methanolic sulfuric acid and benzoylation of the resulting Z-ecgonine methyl ester (125). 

He confirmed this by a synthesis in eighteen steps. Willstatter synthesised ecgonine (discovered by Wohler), and cocaine from ecgonine by esterifying with methyl alcohol and hydrochloric acid and then benzoylating. Cocaine had, in fact, been prepared from benzoylecgonine and methyl iodide by W. Merck and Z. H. Skraup. ... 

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