II. CHEMISTRY 



97 



the 4 position. Second, the synthesis of 2-amino-4-hydroxypteridine-6-car- 

 boxyhc acid (V) was accompHshed by condensation of 2,4,o-triamino-6- 

 hj'droxj'pyrimidine (II) and ethyl-j8,jS-diethoxy-a-bromopropionate. This 

 reaction also estabhshed the presence of a hydroxyl group in the 4 position 

 of the pteridine. 



Unequivocal proof establishing the 6 position of the carboxyl group in 

 compound V was obtained by degrading the corresponding methyl deriva- 



^COOCjH 

 H,N-Tj^^'^'^i\H: °^^^COOGH, HO 



HjNA^X " HOOC 



OH 



,.N^/N 



Y Y VNH 



CjHjO^H H HI 



^C-C-COOCjHs 

 CjHjO Br 



Q. 



' N HOOC-^.X^X 



OH 

 VI 



OH 



H H O 



I 1 II 

 HOOC-C-N-C 



I 



CHj 



I 

 HOOC-CH2 



H 

 I 

 N-CH. 



NaOH 

 O2 



N 

 OH 



HjSO 



decarboxylation 



NH 



H.c^:r-^"= 



VIII 



Pteroylglutamic acid 



Fig. 1. Chemical reactions leading to the establishment of the structural formula 

 of the pteridine (V) obtained by aerobic alkaline hydrolj-sis of pteroylglutamic 

 acid. 



tive, 2-amino-4-hydrox3'-G-methylpteridine (VII) to give a compound iden- 

 tical ^^•ith 2-amino-5-methylpyrazine (VIII). The corresponding 7-metliyl- 

 pteridine would have yielded 2-amino-6-meth3'lpyrazine instead. Oxidation 

 of 2-amino-4-hydrox5^-6-meth3ipteridine (VII) by alkaline permanganate 

 gave the corresponding 2-amino-4-hydroxypteridine-G-carboxylic acid (V). 

 These reactions are outlined in Fig. 1. 



Hydrolysis with 0.5 N sulfurous acid at room temperature was shown by 

 Ilutchings of a/.--' to rapidly inactivate pteroyltriglutamic acid and give an 



2^ B. L. Ilutchings, E. L. R. Stokstad, J. II. Mowat, J. II. Boothe, C. W. Waller, 

 R. B. Angier, J. Semb, and Y. SubbaRow, J. Am. Chem. Soc. 70, 10 (1948). 



