CHEMISTRY OF PURINES AND PYRIMIDINES 117 



an electron deficiency at positions 2, 4, 6, and, to a smaller extent, at the 

 "meta" or 5-position. Hence, pyrimidine exhibits chemical properties that 

 are analogous^^^ to those of the more thoroughly studied pyridine system. ^^^ 

 The stability is altered by the introduction of electron-donating groups 

 such as amino and hydroxyl, and the following sections deal primarily Avith 

 these derivatives. "Vestiges of the behavior of the parent compound, how- 

 ever, remain; the 2, 4 and 6 position retain their electrophilic character . . .; 

 and substitution by electrophilic reagents is still confined to position 5."^^^ 



a. Stability Towards Acid and Alkali; Transformations; Nitrous Acid 



A practical problem concerning the stability of pyrimJdines and purines 

 is encountered in the acid hj^drolysis of nucleic acids. The liberation of 

 purines is achieved under much milder conditions than are needed for 

 pyrimidines (Chapters 5-7, 9-11). The usual procedure, A'' acid at 100° 

 for 1 hour, leads, essentially, to a quantitative recovery of the nucleic acid 

 purines as judged by chromatography^^^ and differential spectroscopy .^^^ 

 However, the isotope dilution technique reveals^^^ that this treatment re- 

 sults in a 7 to 8 % deamination of adenine and guanine. A considerable 

 hydrolytic conversion of cytosine to uracil occurs during a 90-minute heat- 

 ing (175°) with 10 % HCl, but uracil and thymine escape destruction under 

 these circumstances.^^" 5-Methylcytosine is hydrolyzed to thymine by 20 % 

 sulfuric acid at 150-160°.^^ No detectable destruction of uracil, cytosine, 

 or thymine is observed upon heating with 98-100% formic acid at 175° 

 for 30-120 minutes f°'^^° the same is true for adenine and guanine during a 

 30-minutes treatment.'"^ A quantitative recovery of adenine, guanine, cjrto- 

 sine, uracil, and thymine is obtained''^ when these compounds are subjected 

 to the action of 12 A'' perchloric acid at 100° for 1 hour, but 5-hydroxy- 

 methylcytosine is thus destroyed^^ and a 15 % loss of thymine results when 

 the temperature is raised to 110°." (See addendum). 



When guanine is refluxed for 32 hours vnih. 25% hydrochloric acid, a 

 50 % yield of xanthine is obtained ;^^^ a similar treatment of isoguanine for 

 47 hours also affords about a 50% conversion to xanthine.^^^'''^^ When 

 guanine is heated with 3.4 A^ HCl at 158° for 90 minutes, xanthine (52 % 

 yield), ammonia, glycine (53% of the theoretical yield), 4-(or 5-)guanido- 

 imidazole (14%), and a small quantity of glycocyamine are formed. It has 

 been demonstrated with isotopically labeled guanine that the carboxyl, 



329 H. S. Mosher, in "Heterocyclic Compounds" (Elderfield, ed.), Vol. 1, p. 397. Wiley, 



New York, 1950. 

 '30 E. Vischer and E. Chargaff, /. Biol. Chfim. 176, 715, 703 (1948). 



331 H. S. Loring, J. L. Fairley, H. W. Bortner, and H. L. Seagran, /. Biol. Chem. 197, 

 809 (1952). 



332 R. Abrams, Arch. Biochem. 30, 44 (1951). 



333 E. Fischer, Ber. 43, 805 (1910). 



