128 



AARON BENDICH 



OH 



SH 



NH, 



P2S5 



N 



HO 

 Uracil 



boiling 

 xylene 



N 



HS 

 Dithiouracil 



NH3H2O 

 100° 



> N 



HS 



2-Cytosinethiol 



NH, 



HOOCCHia 

 H2O 100° 



NHo 



N 



Cone. 



HCl 



/ 



HOOCCH2S 



2-Carbox3'methylthiocytosine 



N 



I 



/\N/ 

 HO 



Cytosine 



The carboxymethylthiopyrimidines easily form from chloroacetic acid and 

 mercaptopyrimidines and exhibit an extreme range of stabiUty towards 

 g^(.j^ 182 ,245 ,420 Coiwenient syntheses of 2-C'Mabeled uracil and thymine^' 

 exploit the ease with which the Wheeler-Liddle desulfurization proceeds 

 with the 2-thio derivatives. 



An unwanted mercapto group may be replaced by a hydrogen atom by 

 treatment with Raney nickel. 4,5-Diamino-6-hydroxypyrimidine was ob- 

 tained from its 2-mercapto derivative in the first application of this tech- 

 nique to pyrimidines.-*^^ Other examples of compounds prepared by 

 reductive desulfurization with Raney nickel are 4 (or 6) -amino- and 4 (or 

 6)-hj^droxypyrimidine/22 '^'^ 4 ,5-diaminopyTimidine,'*^* 4-hydroxy-6-methyl- 

 pyrimidine,^^^ and pyrimidine.^'^ 



Another method for the sjmthesis of mercapto derivatives proceeds from 

 the interaction of a halo derivative with thiourea in boiling ethanol solution, 

 2-Mercapto-, 4-mercapto-, and dithiouracil are obtained directly from the 

 corresponding chloropyrimidines without isolation of the intermediate 

 thiouronium salts.^-^ The thiouronium salt from 2-chloro-4,6-dimethyl- 

 pyrimidine and thiourea can be isolated, and this yields the 2-mercapto 

 derivative upon alkaline hydrolysis. Thiourea transforms 2 , 5-dichloro- into 

 2-mercapto-5-chloro-pyrimidine.*^* This reaction is an example of the rela- 

 tive stability of halogen atoms at C-5 of pyrimidines."'^^*'^-^ 



«o G. H. Hitchings and P. B. Russell, /. Chem. Soc. 1949, 2454. 



«i L. L. Bennett, J. Am. Chem. Soc. 74, 2432 (1952). 



«2 L. F. Cavalieri and A. Bendich, /. Am. Chan. Soc. 72, 2587 (1950). 



^" D. J. Brown, /. Appl. Chem. (London) 2, 239 (1952). 



«4 J. F. W. McOmie and M. P. V. Boarland, Chemistry & Industry 1950, 602; /. Chem. 



Soc. 1951, 1218; 1952,3722. 

 *" M. Yanai, /. Pharm. Soc. Japan 62, 95 (1942). 



