230 PYRIDOXINE AND RELATED COMPOUNDS 



with the methoxy vitamin. Kuhn and Wendt^^ had previously shown that 

 treatment of the methyl ether of pyridoxine with HBr not only hydrolyzes 

 the ether but also replaces the hydroxyl groups in the hydroxymethyl 

 groups with Br which could be replaced by hydroxyl groups by use of silver 

 acetate. Pyridoxine as its hydrochloride was crystallized from dilute hydro- 

 chloric acid by the addition of acetone. 



b. Harris and Folkers 



Following their announcement in 1939-^ of their synthesis of pyridoxine, 

 Harris and Folkers published their original method of synthesis. ^^ They 

 later described an improved and more practical synthesis. ^^ 



The original synthesis started with the condensation of ethoxyacetylace- 

 tone with cyanoacetamide to yield 3-cyano-4-ethoxymethyl-6-methyl-2- 

 pyridone. The following is the graphic representation of the various steps 

 of the synthesis. 



CHjOCsHb 



II II II pyridine t<^CN HNO, 



CH3CCH,-C-CH.0C,H, + CNCH,-C-NH, JLtaiyst * h.cI JL=0 "^^^ 



H 



CH2OC2H5 CHjOCsHs CHsOCH. 



OjNtj^^CN PCU OsNrj-^CN H,+Pt ^ HjNir^^CN H^+Pd^ 



H,clj^>0 HaClj^Jci H,cl^^Cl 



H 



CHjOCsHj CH2OC2H, CHjBr 



HiNtT^CH^NHj HONG ^ HOf^=^CHjOH HBr ^ HOfr^CH^Br 



CH20H 



H.o ^ HOr^CH^OH 



AgCl HaCk^J 



I 



HCl 



Synthesis of Pyridoxine"' ^'^ 



c. Other Syntheses 



Morii and Makino^^ reported their synthesis of pyridoxine by practically 

 the same method used by Harris and Folkers. Later Mowat et al}^' ^^ also 



" R. Kuhn .•uhI ({. Wendt, Ber. 72B, 811 (1939). 



26 S. A. Harris imd K. Folkers, Science 89, 347 (1939). 



" S. A. Harris and K. Folkers, J. xim. Chcm. Soc. 61, 1245 (1939). 



2" S. A. Harris and K. Folkers, /. Am. Chem. Soc. 61, 3307 (1939). 



'-^ S. Morii and K. Makino, Enztjmolo(iia 7, 385 (1939). 



■'" J. 11. Mowat, F. J. Pilgrim, and G. H. Carlson, J. Am. Chcm. Soc. 65, 954 (1943). 



3' G. H. Carlson, U. S. Pat. 2,310,167 (1943. 



