111. INDrs'l'KIAl. I'KKPAHATroX 233 



III. Industrial Preparation' 



JOHN C. KERESZTESY 

 A. SYNTHESIS 



At this wiitiiiji; at least one coniniercial method for the synthesis of 

 pyridoxine liythochloride is based on the method used by Harris and 

 Folkers.- ^ In this method an alkoxyacetylacetone is condensed with cyano- 

 acetamide to give 3-eyano-4-alkoxymethyl-6 methyl-2-pyridone. This com- 

 pound on nitration, chlorination, and subseciuent reduction yields 2- 

 methyl-3-amino-4-alkox3^methyl-5-aminomethylpyridine dihydrochloride. 

 On hydrolysis and diazotization, pyridoxine hydrochloride (2-methyl-3-hy- 

 droxy-4,5-di(hydroxymethyl)pyridine hydrochloride) is obtained. 



The major producers of pyridoxine h^'drochloride, the only form in which 

 pyridoxine is commercially available, are the American Cyanamid Co., 

 IIoffman-LaRoche, and Merck & Co., Inc. 



B. PURITY STANDARDS, U.S.P.'^ 



Commercial pyridoxine hydrochloride is produced to meet the following 

 purity standards. 



CsHuNOa • HCl : a white crystaUine powder, stable in air and slowly 

 affected by sunlight. Melts with some decomposition between 204 and 208°; 

 1 g. dissolves in 5 ml. of H2O and in about 90 ml. of ethanol; pH about 3.0. 



Loss of weight on drying over concentrated sulfuric acid in vacuum desic- 

 cator should not exceed 0.5 %. Residue on ignition should not exceed 0.1 %. 

 No ammonia odor when heated at 100° with dilute aqueous caustic and 

 less than 40 p.p.m. of heavy metals, as Pb. 



C. U.S. PRODUCTION 



^ The author wishes to express his appreciation to Dr. Max Tishler for his assistance 



in the assembling of the information of this section. 

 ^U. S. Pat. 2,422,617 (1947). 

 ^U. S. Pat. 2,399,347 (1946). 

 * U. S. Pharmacopeia, 14th revision, p. 900, 1950. 



