NICOTINIC ACID (nIACIN) 



2. ISOLATION OF NICOTINIC ACID 



As already noted, the identity of the PP-factor with nicotinamide 

 and nicotinic acid was first established by Elvehjem et at.} who isolated 

 nicotinamide from a liver extract (Eli Lilly) by molecular distillation. 



Nicotinic acid can readily be isolated from natural sources by 

 extraction of the acidified hydrolysed material with organic solvents. 

 The nicotinic acid can be separated from the extract as such, or in the 

 form of its esters or copper salt. The free acid is obtained from the 

 copper salt by decomposition with hydrogen sulphide. 



Nicotinamide can be isolated from natural sources by aqueous 

 extraction, followed by partial hydrolysis with acid to liberate it 

 from the combined form in which it exists, and then extraction with 

 butanol or chloroform. The extract is fractionated by molecular dis- 

 tillation, nicotinamide distilling at 150 to 160° C. at 5 X io~* mm. 



Reference to Section 2 



I. C. A. Elvehjem, R. J. Madden, F. M. Strong and D. W. WooUey, 

 /. Amer. Chem. Soc, 1937, 59, 1767 ; /. Biol. Chem., 1938, 123, 

 137- 



3. PREPARATION OF NICOTINIC ACID 



Synthesis of Nicotinic Acid 



Nicotinic acid was first prepared in 1867 by C. Huber ^ by the 

 oxidation of the alkaloid, nicotine, and this method is still in use for 

 the commercial preparation of nicotinic acid. Nicotine is obtained 

 from waste tobacco, and is widely employed as an insecticide. H. 

 Weidel,2 A. Pictet and G. Sussdorff,^ E. Winterstein and A. B. Wein- 

 hagen,* and S. M. McElvain and R. Adams ^ used nitric acid for the 

 oxidation, whilst R. Laiblin ^ used potassium permanganate solution 

 which gave a particularly good yield, and Huber et alj used chromic 

 acid. Most of the nicotinic acid crystallises out from the acidified 

 oxidation product, and the remainder (about i %) can be recovered 

 from the filtrate as the sparingly soluble zinc salt.''" 



H. Weidel ^ also prepared nicotinic acid by the oxidation of picoline 

 (a mixture of the ^ and y isomers, b.p. 132 to 140° C, was used) with 

 boiling potassium permanganate solution. He obtained a mixture of 

 nicotinic and picolinic acids, which were separated by conversion to 

 the copper salts ; the copper salt of picolinic acid was less soluble 

 and immediately separated out, whilst the copper salt of nicotinic 

 acid was recovered subsequently from the filtrate. The two copper 

 salts were decomposed with sulphuric acid, yielding free picolinic and 



214 



