474 



NIACIN 



D. SYNTHESIS 

 1. Nicotinic Acid 



a. From Nicotine 



Nicotinic acid can be obtained from nicotine by treatment with fuming 

 nitric acid,^'- with chromic acid,^^ or by permanganate** as indicated below. 

 When nicotine is treated with bromine water, dibromoticonine is formed 

 which decomposes in barium hydroxide solution, through the intermediate 

 indicated in parentheses, to nicotinic acid, methylamine, and malonic acid.*^ 



HaC CH2 ^ . 



I I bromine 



11 -CH^^/CHz ^"^te^ 



0=C 



CHBr 

 1 I 



CBr X=0 



CH3 

 Dibromoticonine 



f^^COOH 

 Nicotinic acid 



= C- 



-CHOH 



Ba(0H)2 



^N 



COH^C=0 

 "N 

 I 

 CH3 



+ CH3NH2 + CH2(COOH)2 



b. From ^-Picoline and Other 3 -Substituted Pyridines 



Nicotinic acid can be synthesized from substituted pyridines such as 

 jS-picoline^"'^- and 3-ethylpyridine^^"^^ by suitable oxidation methods. For 

 example, jS-picoline is refluxed for 2 to 3 hours with H3PO4 and HNO3, the 

 HNO3 and H2O distilled up to 200°, and the oxidation repeated with small 

 portions of HNO3. The final residue is diluted with water, treated with 

 NaOH, giving nicotinic acid.^^ This oxidation may also be carried out with 

 oxygen-containing gases in the presence of catalysts such as V2O5 or V2O5 

 containing small quantities of Fe203,^^ 



;S-Picoline can be prepared by heating glycerol with P2O5 and substances 

 containing ammonia or, better, ammonium phosphate.®* It may also be 



8s R. Laiblin, Ber. 10, 2136 (1877); Ann. 135, (1879). 



^^ V. von Richter, The Chemistry of the Carbon Compounds, Vol. IV, p. 337. Elsevier 



Publishing Co., New York, 1946. 

 90 H. Weidel, Ber. 12, 1992, 2004 (1879). 

 9' H. Ost, J. prakt. Chem. [2]27, 286 (1883). 

 82 E. Seyfferth, /. prakt. Chem. [2]34, 258 (1886). 

 " H. Weidel and K. Hazura, Monatsh. Chem. 3, 783 (1882). 

 8* A. Ladenburg, Ann. 301, 152 (1898). 

 95 A. Wischnegradski, Ber. 12, 1480 (1879). 



9« F. E. Cislak and W. R. Wheeler, U. S. Pat. 2,396,457 (March 12, 1945). 

 " F. E. Cislak and W. R. Wheeler, U. S. Pat. 2,437,938 (March 16, 1948). 

 98 P. Schwarz, Ber. 24, 1676 (1891). 



