PREPARATION 



nicotinic acids respectively. Technical picoline was also used as the 

 starting material by K. Hess and F. Leibbrandt,® but the mixed acids 

 obtained on oxidation were separated by extraction with absolute 

 alcohol, in which nicotinic acid was sparingly soluble. 3-Ethyl- 

 pyridine/o 3-phenyl-pyridine ^^ and 3 : 3'-dipyridyl ^^ have also been 

 used as starting materials for the preparation of nicotinic acid. 



The preparation of nicotinic acid by the oxidation of picoline is, 

 like the oxidation of nicotine, a method now used commercially. It 

 is more economical to purify the j8-picoline prior to oxidation than to 

 separate nicotinic acid from the oxidation products of the other 

 isomers. Purification can be effected by refluxing the technical 

 picoline with phthalic anhydride, acetic anhydride, acetyl chloride, 

 chlorosulphonic acid or sulphur dioxide, with which the y-picoline 

 and 2 : 6-lutidine react ; ^^ by preferentially oxidising thege substances 

 in the vapour phase with air in presence of a vanadium and iron 

 catalyst ; ^* or by removing the lutidine with urea and the y-picoline 

 by heating with benzaldehyde or furfural. ^^ The most attractive 

 technical method of producing nicotinic acid from ^-picoline is one 

 due to the Reilly Tar & Chemical Corp.,i^ j^ which the picoline is 

 oxidised in the vapour phase with air, using vanadium and iron oxides 

 as catalyst. j8-Picoline can also be oxidised by means of sulphuric 

 acid in presence of a selenium compound.^^ 



Yet a third method of preparation was used by Huber et alJ In 

 this, quinoline was oxidised by means of boiling alkaline potassium 

 permanganate solution to quinolinic acid, which slowly lost carbon 

 dioxide on heating at 120° C, and more readily at 150° C, giving a 

 moderate yield of nicotinic acid. Quinoline, alkyl quinolines and 

 isoquinoline can be similarly oxidised by other oxidising agents, such 

 as nitric acid with or without the addition of a catalyst. ^^ Sulphuric 

 acid in presence of a selenium compound, such as selenirmi oxychloride, 

 can also be used for the oxidation of quinoline. ^^ 



The oxidation of unsubstituted quinoline does not give good yields, 

 however, because both the pyridine ring and the benzene ring are 

 oxidised. Derivatives of quinoline substituted in the benzene ring 

 are more suitable, and the oxidation of 8-quinoline-sulphonic acid, 

 8-quinolinol and alizarine indigo blue, for example, gave better yields 

 of nicotinic acid than did the oxidation of quinoline itself. Quino- 

 linol, however, is not recommended, as the oxidation is strongly 

 exothermic and an explosion may result. 5 : 7-Dinitro -8-quinolinol, 

 prepared by nitration of 8-quinolinol, is to be preferred ; this gave a 

 good yield of nicotinic acid on oxidation with nitric acid.^^ 



The oxidation of nicotine, /S-picoline and quinoline to nicotinic acid 

 by means of sulphuric acid in presence of various catalysts was studied 

 by Woodward et al.^^ With nicotine, the best yields were obtained 



215 



