II. CHEMISTRY 



321 



xylidiue into riboflavin by coupling with diazotized aniline and shaking the 

 resulting azo compound with excess alloxantin or dialuric acid in an atmos- 

 phere of nitrogen, hnally oxidizing any leucoribofla\-in by shaking with air. 

 A method involving neither ribose nor alloxan is the following :^^ 3,4- 

 dimethylaniline (I) is reductively condensed in the presence of a palladium 

 catalyst with tetraacetyl-D-ribononitrile (II) with loss of NII3. Ribonitrile 

 can be prepared from ribonic acid via the amide. The formed N-tetraacetyl- 

 D-ribitylamino-3,4-dimethylaniline (III) is coupled with p-nitrophenyldia- 

 zonium chloride, and the product is reduced in the presence of a platinum 

 catalyst to l-N-tetraacetylribitylamino-2-amino-4,5-dimethylbenzene (IV). 

 This compound is then condensed with 5,5-dichlorobarbituric acid (V) 

 to form tetraacetylriboflavin (VI) which is then hydrolyzed to riboflavin. 



CH2OAC 



CH2OAC 



H3C 



H3C 



II (HC0Ac)3 



I 

 CN 



+ 



NHo 



CHoOAc 



+H2 



-NHa 



H3C 



H3C 



III 



(HCOAc)i 



I 

 CH, 



I 

 NH 



CH2OAC 



H3C 



H3C 



IV 



G.T-Dimethyl-Q-benzylisoalloxazine can be formed by heating o,5-di- 

 chlorobarbituric acid in pyridine with l-benzylamino-2-amino-4,5-dimeth- 

 ylbenzene. Similarly, 5-amino-N-ribityl-o-4-xylidine and 5,5-dichlorobarbi- 

 turic acid gi^'es riboflavin in excellent yield. 



Synthesis of Riboflavin-5' -phosphate (flavin mononucleotide, FMN). The 

 phosphorylation of riboflavin with phosphoryl chloride in pyridine provides 



'« iM. Tishler and .J. VV. Wellman (to Merck and Co.), U. S. Pat. 2,261,608 (Nov. 4, 

 1941) [r'..l. 36, 1050 (1942)]; M. Tishler, J. W. Wellman, and K. Ladenburg, /. Am. 

 Chem.Soc.B7, 2165 (1945). 



