476 NIACIN 



e. Other Methods 



Trigonelline (the betaine of 3-pyridinecarboxylic acid) can be converted 

 to nicotinic acid by heating at 200° for 1 to 3 hours with pjaidine hydro- 

 chloride or hydrobromide. Nicotinic acid can be separated as the copper 

 salt which can be decomposed with hydrogen sulfide in formic acid.^^'^'* Trig- 

 onelline may also be converted to nicotinic acid by heating mth hydro- 

 chloric acid in a closed tube at 260°'" or by heating in a mixture of potas- 

 sium hydroxide and ammonia."- 



/. Isofopic Nicotinic Acid 



Murray et a/."^ have prepared carboxyl-labeled nicotinic acid in the 

 following fashion with an over-all yield of 60 to 80 % : 



Et20 



+ C*02 



HCL 



-C*OOH 



3-Pyridyl- Nicotinic 



lithium acid 



Nicotinic acid may also be labeled with deuterium. Trenner et a/."^ have 

 described a procedure whereby deuteronicotinic acid can be prepared by 

 direct exchange of nicotinic acid with deuterosulfuric acid. The amount of 

 tracer in the product can be determined using infrared spectroscopy. 



2. Nicotinamide 



a. From Nicotinic Acid 



Nicotinamide can be formed from nicotinic acid by treating with ammo- 

 nia or molten urea at 230°,"*'"^ preferably with a catalyst such as NH4 

 molybdate. 



b. From Esters of Nicotinic Acid 



Esters of nicotinic acid such as the methyl and ethyl esters can be reacted 

 with aqueous or alcoholic ammonia to yield nicotinamide. '°'' n^-i^i 



0" J. Weijhird, J. P. Messerly, and M. Tischler, U. S. Pat . 2,381,794 (August 7, 1945). 



1 E. Jahns, Ber. 20, 2840 (1887). 



2 J. W. Huff, J. Biol. Chem. 166, 581 (1946). 



3 A. Murray, III, W. W. Foreman, and W. Langham, Science 106, 277 (1947). 



■• N. R. Trenner, R. W. Walker, B. Arison, and C. Trumbauer, Anal. Chew. 23, 487 



(1951). 

 5 S. Keimatsu, K. Kokata, and I. Satoda, J. Pharni. Soc. Japan 53, 994 (19.33). 

 « E. Cherbuliez and F. Landolt, Helv. Chim. Acta 29, 1438 (1946). 

 ^ E. F. Pike and R. S. Shane, U. S. Pat. 2,412,749 (December 17, 1946). 



8 P. W. Garbo, U. S. Pat. 2,419,813 (April 29, 1947). 



9 C. Engler, Ber. 27, 1787 (1894). 



20 F. Pollak, Monatsh. Chem. 16, 53 (1895). 



21 F. B. LaForge, J. Am. Chem. Soc. 50, 2.377 (1928). 



