282 



ANNUAL REPORT SMITHSONHAN ESTSTITUTION, 1942 



development of pellagra, a disease that was common in our southern 

 States. It is reported that 400,000 to 500,000 people suffered from 

 this disease every year. Investigations by Elvehjem led to his demon- 

 stration in 1937 that nicotinic acid would cure black tongue in dogs, a 

 condition analogous to pellagra in man. Previous to 1937 nicotinic 

 acid had been isolated from rice polish, liver, etc., but no one had 

 recognized the significance of these findings. In 1938 Spies and his 

 coworkers reported that nicotinic acid (niacin) was effective in the 

 treatment of human pellagra, and its use naturally has spread rapidly. 



E»O0C.CH,CH,0& 



ethyl p-echoxy- 

 propioaate 



N=C — OH 



I I 



CHaC C— CHsOEt 



II II 

 N— CH 



2-inetbyl-5-eihoxynietbyt- 

 6-bydroxypyriniidiae 



+ HCOOft 

 Ethyl formate 



POCI , 



Phojphorui 

 oiychloride 



+ H,N.C(CHj):NH 

 Acetomidine 



EtOOC.CHCHjOEt 

 I 

 O.CH 



Ethyl formyl- 

 P-ethoxypropiooaie 



N=C — CI 



I I 



CHjC C— CH,OEt 



II II 

 N — CH 



2-methyl-5-ethoxy methyl- 

 6-cbloropyrimidme 



N = C - OH 

 i I 

 CHjC C — CH-OEt 

 II II 

 N — CH 



2-metbyl-5-ethoxymethyl- 

 C-hydroxypyriiBidine 



Ale NH, 



m 

 Alcoholic ommonio 



N=C— NHj 



I I 



CHjC C — CHjOEt 



II II 

 N — CH 



2methyl-5-ethosymethyl- 

 C-amiaopyrimidine 



HBr 



Hydrobremic 

 acid 



N = C— NHj 



I I 



CH,C C— CH.OEt 



II II 

 N — CH 



2-nKtbyl-5-e(boxyfnetbxl. 

 6-ainioopyrimidioe 



N: 

 I 

 CH,C 



:C — NHj.HBr 

 C— CH.Br 



N — CH 



2-methyI-5-bromomethyl- 



6-aminopyrimidine 



bydrobromide 



+ 4-Mefhyl.5-p. 



(hydroiyethyl)^ 

 thiotolc 



CHj 

 I* 

 N = C— NHj.HBr C=:C— CH, 



II / I ' 



CHjC C— CH,— N^ CH, 



II II l\ I I 



N — CH Br CH — S OH 



Vjiamin Bi bromide 

 bydrobromide 



Ale. AgCI 



»— 



CH, 

 I 



N=C — NHj.HBr ^C=C — CH 

 11 / I I 



CH,C C— CH, — N, CHj 

 II II IV I I 



N — CH Br ^CH — S OH 



Vitamin Bi bromide 

 bydrobromide 



Alcoholic »il»er chloride 



CH, 

 I 



N = C — NHj.HCI C = C — CH, 



II / I ' 



CH,C C — CH, N. CH, 



II II l\ I I 



N — CH CI CH — S OH 



Vitamin B. chloride 

 hydrochloride 



FiGXJTE 7. — Williams and associates synthesis of vitamin Bi. 



Nicotinic acid was first prepared in 1867 by Huber by the oxidation 

 of nicotine with potassium chromate and sulfuric acid. Later it was 

 found that nitric acid could be used as the oxidizing agent. Nicotinic 

 acid may be made also by other methods, such as the oxidation of 

 quinoline or /3-picoline or by the bromination of pyridine, followed 

 by its conversion to the nitril of nicotinic acid and then by hydrolysis. 

 Nicotinic acid is made in large quantities by processes such as these. 



