II. CHEMISTRY 



10.5 



duct one (L^:^(lilly(l^^)\ya(•l•yUlldehy(^e) to <>;ivc diethyl N-[?j-(2,3-dihy- 

 ilro\y-2-one-i)r()i)ylid(Mioaniin())l)cnzovl) <2;liit:unate. This was thcMi con- 

 densed with 2,4 ,r)-triamino-0-hydro.\ypyrimidine (II) in hotethylene glycol 

 to give pteroylgliitamic acid diethyl ester in 5 to 20 % yield. A number of 

 derivatives of pteroic acid, including the ethyl ester, amide, and pteroyl- 

 glycine, were prepared by this procedure. 



A fourth method, described by Boothe et al.,^^ consists in attaching a pre- 



H H O 



HOOC-C-X-C-V/ \ 

 I 



I 

 HOOC-CH. 



X 



CHO 



I 



p-Aininobenzoylglutamic acid 



H H 

 I I II 

 HOOC-C-N-C- 



I 



I 

 HOOC-CH, 





.JLyN 



Pteroylgliitamic acid 



OH 



.N=. 



NH. -f Br-CH.-C-Br + 2f J T''''^ 



OH 



II 



X in ethylene glycol 



B"^" ^Vv-N= 



H T„ OH 



OH 

 II 



XI 



Fig. 6. Two syntheses of ptero3lgIutamic acid. 



^NH, 



formed pteridine to a derivative of p-aminobenzoic acid. 2-Amino-4-hydrox- 

 y-(3-methyl-pteridine (VII) was prepared by the reduction of 2-amin 0-4-11}''- 

 droxy-G-pteridylmethylpyridinium iodide (XI) wnth zinc in alkaline solution 

 and subsequent oxidation by iodine of the resulting dihydro-2-amino-4-hv- 

 droxy-fi-methylpteridine. This was brominated at 150°, and the resulting 

 crude 2-amino-4-h3'droxy-G-bromomethylpteridine was condensed with p- 

 aminobenzoylglutamic acid diethyl ester in ethylene glycol at 100°. 



35 J. H. Boothe, C. W. Waller, E. L. R. Stokstad, B. L. Hutchings, J. H. Mowat, 

 R. B. Angier, J. Semb, Y. SubbaRow, D. B. Cosulich, M. J. Fahrenbach, M. E. 

 Hultquist, E. Kuh, E. H. Northey, D. R. Seeger, J. P. Sickels, and J. M. Smith, 

 Jr., J. Am. Chcm. Soc. 70, 27 (1948). 



