CHEMISTRY OF PURINES AND PYRIMIDINES 131 



drogenation and Raney nickel desulfurization.^''^ The mercapto group of 2- 

 mercaptohypoxanthine was replaced by hydrogen via nitric acid oxidation 

 in an early synthesis of hypoxanthine.^" Syntheses of adenine may be ef- 

 fected by the nitric acid-hydrogen peroxide oxidation of 2-mercaptoade- 

 nine^° or by desulfurization with Raney nickel. ^^^ 



Other transformations have been utilized in partial syntheses of iso- 

 topically labeled purines. 1,3-Labeled xanthine^^^ '^^^ and hypoxanthine''^^ 

 are obtained from the nitrous acid deamination, respectively, of N'*- 

 guanine and adenine. Stably-bound deuterium or tritium atoms are intro- 

 duced into the adenine and guanine molecules by isotope interchange from 

 heavy water in the presence of a platinum catalyst.'*^^ The isotopes un- 

 doubtedly enter at position 8 of guanine and positions 2 or 8 (or both) 

 of adenine, and the amount of exchange is a function of the isotope content 

 of the aqueous media used. 



An amino group may be introduced into the 8-position of purines un- 

 substituted at C-8 by coupling \\'ith 2,4-dichlorobenzenediazonium chloride 

 and reducing the resulting diazo compound with sodium hydrosulfite.'*^^'^^- 

 For other transformations including methylations on ring nitrogen, see 

 Fischer,^ Johnson,'^ and Biltz.'®^ 



h. From Pyrimidines 



The most versatile and widely used method for the synthesis of purines 

 was developed in 1900 by Traube.^^ This method may be considered to 

 consist of two parts: (a) the preparation of the appropriate 4,5-diamino- 

 pyrimidine, and (b) ring closure to the purine. Traube introduced the 

 amino group into the 5-position of 4-amino-6-hydroxy- and 4,6-diamino- 

 pyrimidines (bearing a mercapto, hydroxyl, or amino group at C-2) by 

 nitrosation (cf. Lythgoe et al}^^) followed by ammonium sulfide reduction. 

 Variations of this method include reduction of the nitroso group with 

 hydrosulfite,^^-''^^''^^ the use of 5-nitro derivatives and their subsequent 

 reduction to amines,"^ ^^^^^^■^-^•''^^ the use of 5-arylazopyrimidines which 

 are readily reduced to S-aminopyrimidines,^^^"*^* and the use of hydrolyzable 



"• H. Getler, P. M. Roll, J. F. Tinker, and G. B. Brown, J. Biol. Chem. 178, 259 (1949). 



«2 M. L. Eidinoff and J. E. Knoll, /. Am. Chem. Soc. 75, 1992 (1953). 



«3 J. R. Spies and T. H. Harris, Jr., ./. Am. Chem. Soc. 61, 351 (1939). 



«" M. F. Mallette, E. C. Taylor, and C. K. Cain, /. Atn. Chem. Soc. 69, 1814 (1947) ; see 

 also 68, 1996 (1946). 



«5 R. K. Robins, K. J. Dille, C. H. Willits, and B. E. Christensen, J. Am. Chem. Soc. 

 75, 263 (1953); see correction, p. 6359. 



«6 J. Baddiley, B. Lythgoe, and A. R. Todd, /. Chem. Soc. 1943, 386. 



«7 B. Lythgoe, A. R. Todd, and A. Topham, /. Chem. Soc. 1944, 315. 



«» L. F. Cavalieri, J. F. Tinker, and A. Bendich, /. Am. Chem. Soc. 71, 533 (1949); cor- 

 rection: 72, 5801 (1950). 



