NICOTINIC ACID (NIACIN) 



with selenium ; j8-picoline gave lower yields than either nicotine or 

 quinoline. 



Other methods are available for the preparation of nicotinic acid. 

 Thus O. Fischer ^^ obtained it from pyridine via pyxidine-sulphonic 

 acid and cyano-pyridine but the overall yield was not good, and a 

 better route was suggested by S. M. McElvain and M. A. Goese,^^ in 

 which pyridine was treated with bromine and hydrobromic acid to 

 yield a dark red perbromide ; this, when heated at 300° C, yielded 

 ^-bromopyridine, which, when heated with cuprous cyanide at about 

 170° C, was converted into 3-cyanopyridine. This can be hydrolysed 

 as in Fischer's method with acid, or by means of alcoholic sodium 

 hydroxide solution to nicotinic acid. 



Synthesis of Nicotinamide 



Nicotinamide was first prepared in 1894 by reacting ethyl nico- 

 tinate with concentrated ammonia ; ^^ details of a more recent modi- 

 fication of this method were given by F. B. LaForge.^* It can also 

 be made by treating the acid chloride with ammonia ; by passing 

 ammonia gas into nicotinic acid at 230° C.,^^ or spraying molten ammon- 

 ium nicotinate into ammonia gas at 140-200° C.^^ ; by the action of 

 ammonium polysulphide on 3-acetylpyridine ^^ ; or by reacting nicotinic 

 acid with urea,^^ preferably in presence of a molybenum catalyst.^* 

 A useful technical process is based on the partial hydrolysis of 3-cyano- 

 pyridine with mineral acid ^^ or with dilute sodium hydroxide solution, 

 sodium carbonate solution or triethylamine in presence of hydrogen 

 peroxide. 31 3-Cyanopyridine can also be converted into nicotinamide 

 by boiling an aqueous solution with the quaternary ammonium 

 hydroxide resin, IRA — 400 ; an 86 to 90 % yield is claimed.^i" 

 Nicotinamide was produced in low yield when asparagine was heated 

 with glutamic acid and perhaps with other acids. ^^ 



References to Section 3 



1. C. Ruber, Annalen, 1867, 141, 271 ; Ber., 1870, 3, 849. 



2. H. Weidel, Annalen, 1873, 165, 331, 346. 



3. A. Pictet and G. Sussdorff, Arch. sci. phys. nat. (4), 1898, 6, 113. 



4. E. Winterstein and A. B. Weinhagen, Helv. Chim. Acta, 191 7, 100, 



181. 



5. S. M. McElvain and R. Adams, /. Amer. Chem. Soc, 1923, 45, 2738. 



6. R. Laiblin, Annalen., 1879, 196, 135. 



7. C. Huber, S. Hoogewerff and W. A. van Dorp, Rec. Trav. Chim. 



Pays-Bas, 1882, 1, 121. 

 7a. American Cyanamid Co., U.S. P. 2447234. 



8. H. Weidel, Ber., 1879, 12, 1992. 2004. 



9. K. Hess and F. Leibbrandt, ibid., 191 7, 50, 385. 



216 



