A new synthesis of cytosine and 5-methylcytosine.

The chief difficulty in the way of a fruitful synthesis of cytosine from uracil is the essentially equal reactivities of chlorine atoms and of ethoxyl groups in the 2 and 4 positions of the pyrimidine nucleus. The reaction of 2,4-dichloropyrimidine with ammonia leads to a mixture of chloroaminopyrimidines (1) which is separable only after transformation to the methoxyaminopyrimidines. The reaction of dichloropyrimidine with sodium ethoxide has been offered as an alternative (2), since the diethoxypyrimidine so formed, on further treatment with sodium ethoxide, is converted to a mixture of ethoxyhydroxypyrimidines, the sodium salts of which are separable. Since the ethoxyl groups are replaceable by amino groups, the individual isomers can be converted to cytosine and isocytosine respectively. Both methods have been used in preference to the original method of Wheeler and Johnson (3, 4) which proceeds from 2-ethylmercapto-4hydroxypyrimidines via chlorination, amination, and subsequent hydrolysis of the ethylmercapto grouping. The discovery that the 4-thiol group of 2,4-dithiolpyrimidines is much more reactive toward ammonia and amines than is the 2-thiol group’ has opened up a new route to the synthesis of 4-aminopyrimidine derivatives. The ready availability of dithiolpyrimidines from thiol-, hydroxy-, and