CHEMISTRY OF PURINES AND PYRIMIDINES 



87 



syntheses of thymine,'*^ "^^ one of which'^^ is illustrated: 



O 



C2H5OC 



CH3 



NH2 



C 



+ 



KOH, H2O 

 room temp. 



CH3S NH 



iS-Methvlthiourea 



C 



/ \ 

 HO H 



Eth}'! formyl 

 propionate 

 (enol form) 



OH 



OH 



CHj 



// 



N 



CH3 



cone. HCl 



reflux 10 hr. 



CH3S 



2-Methylmercapto- 



5-methyI-6-hydroxy- 



pyrimidine (20% yield) 



N 



\n/ 



HO 



Thymine 

 (99% yield) 



Thymine, a ubiquitous component of the deoxy type of nucleic acid (see 

 Chapters 4 and 10), has not yet been found in the pentose nucleic acids or 

 in the free state in natural sources, although it has been isolated as an 

 A^'-xyloside (spongothymidine) from sponges (see below). 



In 1894, Kossel and Neumann also^^ discovered as a cleavage product of 

 calf thymus nucleic acid a basic substance which they named cytosine 

 (2-hydroxy-6-aminopyrimidine, XII). ^^ Certain of its salts were described*^ 

 ^^■^> and this led to its correct empirical composition. Since uracil was 

 obtained from nitrous acid deamination, and biuret (rather than guanidine) 

 from permanganate oxidation, Kossel and SteudeP' proposed the accepted 

 structure of cytosine. The synthesis of cytosine^^ furnished further proof 

 of its structure. The synthesis is analogous to that for thymine previously 

 described above in that *S-ethylthiourea and ethyl formylacetate were 



4^ H. Steudel, Z. physiol. Chem. 32, 241 (1901). 



« H. L. Wheeler and H. F. Merriam, Am. Chem. J. 29, 478 (1903). 



« O. Gerngross, Ber. 38, 3408 (1905). 



" H. L. Wheeler and D. F. McFarland, Am. Chem. J. 43, 19 (1910). 



« Beilstein, 24, 314 (1936). 



'' A. Kossel and H. Steudel, Z. physiol Chem. 37, 177, 377 (1902-03). 



5" P. A. Levene, Z. physio! . Chem. 38, 80 (1903). 



" A. Kossel and H. Steudel, Z. physiol. Chem. 38, 49 (1903). 



« W. L. Wheeler and T. B. Johnson, Am. Chem. J. 29, 492 (1903). 



