GB660197A - Alkyl-mercaptoalkanoates of hydroxylated hormones - Google Patents

Abstract

Esters of hydroxylated hormones of the cyclopentanophenanthrene and stilboestrol series are prepared by reacting the hormone in the presence of a base with an alkylmercaptoalkanoyl halide having the general formula R-S-X-CO-Y where R is an alkyl group containing one to four carbon atoms, X is an alkylene group containing one to three carbon atoms and Y is a halogen, or with an alkylmercaptoalkanoic anhydride of the general formula (R-S-X-CO)2O where R and X are as above defined. Hormones mentioned include testosterone, oestradiol, oestrone, stilboestrol and desoxycorticosterone. Esters mentioned include the methylmercaptoacetate, ethylmercaptoacetate, n - propylmercaptoacetate, n - butylmercaptoacetate, 3 - (2 - propylmercapto) - propanoate, 4 - (n - propylmercapto) - butanoate, 2 - methylmercaptopropanoate, 2 - ethylmercaptobutanoate, and the 3-(n-propylmercapto)-butanoate. The preferred basic agents are pyridine and fused potassium acetate. Examples are given of the production of the following compounds and their physical constants recorded. (1) Testosterone alkylmercaptoalkanoates: the 2-methyl mercaptopropanoate, ethylmercaptoacetate, 2-ethyl - mercaptopropanoate, methylmercaptoacetate, n - propylmercaptoacetate, (2 - propyl) - mercaptoacetate, n - butylmercaptoacetate, 3 - methylmercaptopropanoate, 2-methylmercaptobutanoate, 4-methylmercaptobutanoate and 4-n-propylmercaptobutanoate. (2) Stilboestrol alkylmercaptoalkanoates: the bis-(ethylmercaptoacetate). The alkylmercaptoalkanoic acids used as intermediate compounds may be obtained by either (a) the alkylation of a mercaptoalkanoic acid, or (b) the treatment of a haloalkanoic acid, or a haloalkanenitrile with an alkanethiol under alkaline conditions. Procedure (a) is illustrated by the interaction of dimethyl sulphate and 2-mercaptopropanoic acid in the presence sodium hydroxide to give 2-methylmercaptopropanoic acid, and procedure (b) by the interaction of methanethiol and 2-bromobutanoic acid in the presence of sodium hydroxide to give 2-methylmercaptobutanoic acid, and 1-propanethiol and 4-chlorobutanenitrile to give 4-n-propylmercaptobutanoic acid. Other compounds mentioned include n-propylmercaptoacetic acid, (2-propyl)-mercaptoacetic acid, and n-butylmercaptoacetic acid. The alkylmercaptoalkanoic acid halides are prepared from the corresponding alkylmercaptoalkanoic acids and (a) either thionyl chloride, or (b) phosphorus trichloride. The preparation of n-propylmercaptoacetyl chloride by method (a) is described and the preparation of 2-methylmercaptobutanoyl chloride by method (b). p Ethylmercaptoacetic anhydride is prepared by refluxing ethylmercaptoacetic acid and acetic anhydride.