PYRIDOXINE 



CHaOEt 

 {b) 8 I CH2OE 



ll I 



CH.CN . II I 



CH3.CO + CO 



H20 



-co 



HN03 



mi 



N ^O N ^O 



H H 



CH2-O CH2-O CH2-O 



u 



CO ^^, O^n/ ^CO ^ H^Nif ^— CO 



H 



PCI5 ^-=11 ^^ Ha ""2-^11 I — HNO2 



^ CH3II jci ' CH3II J 



CH2OH 



'\— CO ^\ HOjj \cH2OH 



HOf 



CH3I!, ) CU,^ ^ 



{c) » the method of S. A. Harris and K. Folkers ^ (page 301) ; 



[d] ^^ the same method using dilute hydrochloric acid under pressure 

 instead of hydrobromic acid to hydrolyse the ethoxymethyl group ; this 

 simplifies the process by eliminating the final step, i.e. the conversion of 

 the bisbromomethyl compound into pyridoxin e ; 



[e) 11 the same method in which the amino-group is protected by 

 acetylation prior to the chlorination. 



The preparation of the dimethyl ester of 3-methoxy-2-methyl- 

 cinchomeronic acid : 



COOMe 



CHaO/^' 



CH. 



COOMe 



V 



for use in the synthesis of pyridoxine was also patented by Merck 

 & C0./2 who also protected 13 the preparation of 4 : 5-epoxydimethyl- 

 3-hydroxy-2-methyl-pyridine by acid treatment of 4-alkoxymethyl-3- 

 hydroxy-5-hydroxymethyl-2-methyl-pyridine, and its conversion into 

 4 : 5-di-(halomethyl)-3-hydroxy-2-methyl-pyridine by heating with 

 hydrogen halide. 



They also patented ^^ the preparation of pyracin (see page 344) by 

 oxidising a salt of 3-hydroxy-4 : 5-di-(hydroxymethyl)-2-methyl- 

 pyridine with aqueous potassium permanganate solution. This can 

 be methylated with diazomethane. 



304 



