II. CHEMISTRY 477 



c. From S-Ci/anopyridine 



Nicotinamide can be produced directly from the above compound by 

 partial hydrolysis in an aqueous alkaline solution containing a sufficient 

 quantity of alkali to produce a larger portion of nicotinamide than nicotinic 

 acid but insufficient to complete the h^^drolysis of the cyanopyridine.^'-- ^-^ 

 Nicotinamide can also be produced from this compound by treating with 

 H2O2 and NaOH^-^ or by heating the compound with water, NH3, or an 

 amine. ^^^ 



3. Synthesis of Related Compounds of Biological Importance 



a. S-Acetylpyridine 



Ethylnicotinate undergoes normal Claisen-tj^pe condensations. With 

 ethyl acetate in the presence of sodium ethoxide, ethylnicotinoacetate 

 is formed in good yield. 



O 



-C— O— C2H5 II ^ ^— C— CH2C— OC2H5 



+ CH3C— 0C.H5 Ji^?i, 



The latter may be hydrolyzed to 3-acetylpyridine in excellent yield using 

 hydrochloric acid.^^' ^-^ 



O 



II II II 



C— CHo— C— OC2H5 C— CH3 



+ CO., H C^JIoOH 



b. N^-Methylnicotinamide , 



Nicotinamide (and nicotinic acid) react readily with methyl iodide and 

 similar alkyl iodides to yield the corresponding N '-substituted deriva- 

 tives.^^' ^® These may then be converted to the corresponding chloride (the 

 form in which this compound is ordinarily used) by treatment with silver 

 chloride. 



'22 British Pat. 563,184 (August 2, 1944) [C. .4. 40, 2473 (1946)]. 



'23 B. F. Duesel and H. L. Friedman, U. S. Pat. 2,471,518 (May 31, 1949). 



'2^ J. F. Couch and C. F. Kreevson, U. S. Pat. 2,453,496 (November 9, 1948). 



'25 H. R. Rosenberg, U. S. Pat. 2,446,957 (August 10, 1948). 



'26 H. Oilman and H. S. Broadbent, J. Am. Chem. Soc. 70, 2755 (1948). 



