II. CHEMISTRY 473 



in the /3 position of the pyridine ring specifically faciHtates the reversible 

 reduction of corresponding pjn'idininm salts. 



3. Other Compounds Related to Xicotixic Acid 



The properties of several compounds related to nicotinic acid are listed 

 in Table I. 



C. CONSTITUTION OF NICOTINIC ACID 



The structure of nicotinic acid was determined shortly after it was first 

 isolated from the oxidation products of nicotine.*^' ^'^ The presence of a 

 pyridine ring can be established by boiling nicotinic acid with calcium hy- 

 droxide. Carbon dixoide is split off and free pyridine obtained. The car- 

 boxylic acid group can be identified by the formation of metallic salts and 

 by the formation of derivatives such as esters and the acid chloride (see 

 pp. 4G4-6). The existence of the basic ring nitrogen can be inferred bj^ the 

 formation of salts such as the hydrochloride and the hydrobromide and 

 by the formation of (juaternary ammonium compounds such as nicotinic 

 acid methochloride and methoiodide. 



The fact that the carboxylic acid group was in the 3 (l3) position was 

 proved by Skraup and CobenzP^- ^* by oxidation of 3-phenylpyridine the 

 structure of which was proven. Benzo[/jquinoline was oxidized to 3-phen- 

 ylpyridinecarboxylic acid, from which 3-phenylpyridine was formed by 

 decarboxylation. This in turn oxidized to nicotinic acid.*^' ^^ The 3 position 

 of the carboxyl group was further established by the formation of nicotinic 

 acid from synthetically prepared m-dipyridyl.^^ 



Simpler proof of the constitution of nicotinic acid is cited by \'on Richter*^ 

 from the behavior of 2,3-pyridinedicarboxylic acid (riuinolinic acid) and 

 3,4-pyridinedicarboxylic acid (cinchomeronic acid). When the former is 

 heated, nicotinic acid is formed by elimination of one carbon dioxide group. 

 When the latter is heated, both nicotinic acid and isonicotinic acid (4-pyri- 

 dinecarboxylic acid) are formed. Therefore nicotinic acid is 3-pyridine- 

 carboxjdic acid. 



" C. Huber, Ber. 3, 849 (1870); Ann. 141, 271 (1867). 



82 H. Weidel, Ann. .165, 331, 346 (1873). 



83 Z. H. Skraup, Monalsh. Chnn. 1, 800 (1880). 



" Z. H. Skraup and A. Cobeiizl, Monatsh. Chem. i, 436 (1883). 



85 V. voii Hichter, The Chemistry of the Carbon Compounds, Vol. IV, p. 214. Elsevier 



I'ublishing Co., New York, 1946. 

 8" II. H. Ko.senberg, Chemistry and Physiolog;y of the Vitamins, j). 223. Interscience 



I'ulilishers, New York, 1942. 

 '"' Z. II. Skraup and (!. \'ortmann, Mondtfth Chcni. 4, 594 (1883). 



