228 PYRIDOXINE AND RELATED COMPOUNDS 



through the oxidative degradation of the methyl ether of pyridoxine or 

 adermin, the name used by the German workers. On oxidation of the methyl 

 ether, the lactone, the same as that of Stiller, Keresztesy, and Stevens, 

 was obtained. On more vigorous oxidation with hot permanganate, a tri- 

 carboxylic acid resulted which could be degraded to the dicarboxylic acid. 

 Since the tricarboxylic acid gave a red color with ferrous sulfate, a test for 

 pyridine-a-carboxylic acids, and since the dicarboxylic acid did not give a 

 color with the reagent, it was concluded that the CO2 had been split off 

 from the a position on the pyridine ring. Pyridoxine gave a deep blue color 

 with the Folin-Dennis phenol reagent. On the other hand, this test with 

 the methyl ether was negative. Thus the compound was a j8-hydroxypyri- 

 dine derivative. Furthermore, the formation of a lactone of the partially 

 oxidized methyl ether of pyridoxine indicated that in the vitamin two of 

 the original hydroxymethyl groups were located on adjacent carbon atoms 

 in the pyridine nucleus. The final proof that the dicarboxylic acid oxidation 

 product of the methyl ether of pyridoxine was identical with synthetic 2- 

 methyl-3-methoxypyridine-4 , 5-dicarboxylic acid was accomplished by 

 Kuhn et al?^ by its preparation from 3-methyl-4-methoxyisoquinoline. 



c. Ichiha and Michi 



Ichiba and Michi^^"^^ in studying the chemistry of pyridoxine were led 

 to believe at first that the vitamin was either an a- or 7-hydroxypyridine 

 derivative by the enolic nature of the hydroxyl group. On methylation of 

 the vitamin with diazomethane they obtained the N-methyl compound 

 which still gave a red coloration with ferric chloride. The formation of the 

 N-methyl derivative substantiated the claim of Stiller, Keresztesy, and 

 Stevens^^ that the vitamin is amphoteric in nature as opposed to the con- 

 cept of Kuhn and Wendt,^^ who considered changes in the ultraviolet ab- 

 sorption spectra as merely reversible shifting of the maxima. 



Ichiba and Michi^^ also synthesized the key compound, i.e., 2-methyl-3- 

 methoxypyridine-4 , 5-dicarboxylic acid. After preparing 2-methyl-3-meth- 

 oxy-1-chloioisoquinoline, they reduced this compound to 2-methyl-3-meth- 

 oxyisoquinoline, which on oxidation yielded the desired dicarboxylic acid 

 which they found to be identical with that obtained by the oxidation of the 

 methyl ether of pyridoxine. 



21 R. Kuhn, K. Westphal, G. Wendt, and O. Westphal, Naturwissenschaften 27, 469 

 (1939). 



22 A. Ichiba and K. Michi, Set. Papers Inst. Phys. Chem. Research {Tokyo) 35, 73 

 (1938). 



23 A. Ichiba and K. Michi, Sci. Papers Inst. Phys. Chem. Research {Tokyo) 36, 1 

 (1939). 



^^ A. Ichiba and K. Michi, Sci. Papers Inst. Phys. Chem. Research {Tokyo) 36, 173 

 (1939). 



