316 



RIBOFLAVIN 



CI 



NHCH2(CHOH)„CH20H 



V\ 



+H2NCH2(CHOH)nCH20H 

 -HCl 



+ H, 



NOs 



NO2 



NHCH2(CHOH)„CH20H 



NH2 



responding sugars in liquid ammonia containing 3 % of water, over a Raney 

 nickel catalyst at 85° and 200 p.s.i." 



9-(|S-Hydroxyethyl)isoalloxazine,^^ 6-nitro-9-(/3-hydroxyethyl)isoaloxa- 

 zine, 9-(/3-diethylaminoethyl)isoalloxazine, 6-nitro-9-(/3-diethylaminoethyl) 

 isoalloxazine, and other basically substituted isoalloxazines^^ have been 

 prepared by this method. 9-(Dialkylaminoalkyl)isoalloxazines, the free 

 bases, differ chemically from riboflavin by their solubility in organic sol- 

 vents, for instance CHCI3 . 



(3) Another method for the synthesis of substituted 2-nitroanilines which 

 are needed for the synthesis of riboflavin is the condensation of substituted 

 o-dinitrobenzene with sugar amines. For instance, o-dinitroxylene and riba- 

 mine are condensed in aqueous alcoholic solution and catalytically reduced 

 to the corresponding diamine. The over-all yield of riboflavin amounted to 

 4.5% of the ribose used.^^ 



H3C 



H3C 



NO2 



NO5 



-1-H2NR 



H3C 



H3C 



NHR 



NO 5 



+H, 



HsC 



HaC 



NHR 



NH2 



3-Methylriboflavin^^ and, recently, 6,7-dichloro-9-(l'-D-sorbityl)isoalox- 

 azine and its analogs have been synthesized by this method ; a variant uses 

 substituted o-iodonitro-benzenes as starting materials. ^^ 



(4) A fourth method of riboflavin synthesis starts with the condensation 

 of 3 , 4-xylidine with D-ribose by boiling the amine and the sugar in alcoholic 



66 R. B. Flint and P. L. Salzberg, U. S. Pat. 2,016,962 (1932); F. W. Holly, E. W. Peel. 

 K. Folkers et al. J. Am. Chem. Soc. 72, 5416 (1950); 73, 332 (1951); 74, 4047 (1952). 

 6« F. Kipnis, N. Weiner, and P. E. Spoerri, J. Am. Chem. Soc. 69, 799 (1947). 

 " R. Kuhn and F. Weygand, Ber. 68, 1001 (1935). 



68 R. Kuhn, K. Reinemund, F. Weygand, and R. Strohele, Ber. 68, 1765 (1935). 



69 F. W. Holly, E. W. Peel, R. Mozingo, J. J. Cahill, F. R. Koniuszy, C. H. Shunk, 

 and K. Folkers, J. Am. Chem. Soc. 72, 541G (1950); 74, 4047, 4251 (1952). 



