420 THIAMINE 



in ethereal solution under cooling with phosphorus pentasulfide and got the 

 crude product with a yield of 40 to 45 %. As thioformamide is ^-ery unstable 

 in crystalline state, only a concentrate is prepared for technical purposes. 

 Gabriel improved the method a little by using larger amounts of phosphorus 

 pentasulfide,^^ but even then the crude product contained only 36 % of 

 sulfur (theory 52.5%). Most of the workers in the thiamine field have use 

 the Willstatter-Gabriel method. 



Todd ct al}'' claim a superior way by reacting free dithioformic acid in 

 ether with aqueous ammonia. A yield as high as 50 % is claimed in a United 

 States patent .^^ 



CHSSH + 2NH3 = CHSNH2 + NH4SH 



Dithioformic acid is technically available,^^ but it is not known if the 

 method is used for the production of thioformamide. 



h. For Closing the ThiazoUum Ring 



If, instead of thioformamide, compounds with a substituted amino group 

 are used, thiazolium salts are obtained instead of thiazole. The compound 

 necessary for this kind of thiamine synthesis, 2-methyl-4-amino-5-thio- 

 formylaminomethylpyrimidine, can be obtained via formylation of 2- 



N=C— NHo 



I I 



CH3— C C— CH2— NHCH=S 



II II 

 N— CH 



methyl-4-amino-5-aminomethylpyrimidine; as has been known for a long 

 time,^" the 4-amino group remains untouched and only the 5-form3damino- 

 methyl compound is formed. This in turn can be transformed to the thio- 

 formylaminomethyl by means of phosphorus pentasulfide,-^ but the yields 

 of this step are extremely poor. 



It was one of the greatest improvements in the synthesis of thiamine 

 when Todd et al. found a simple method for the thioformylation of amines.^^ 



Dithioformic acid is obtained as potassium salt when potassium sulfide 

 (from potassium hydroxide and hydrogen sulfide) in alcoholic solution is 



HCCI3 + 2K2S = HCSSK + 3KC1 



reacted with chloroform. ^^ The yield in the hands of the British workers 

 was about 45 % in the form of recrystallized salt. 



« S. Gabriel, Ber. 49, 1115 (1916). 



" A. R. Todd, F. Bergel, and Karimullah, Ber. 69, 217 (1936); A. R. Todd, F. Bergel, 



Karimullah, and R. Keller, /. Chem. Soc. 1937, 361. 

 ^8 M. Hoffer, U.S. Fat. 2,220,243, ex. 4 (November 5, 1940). 

 " Levi, Atti reale accad. naz. Lincei 32, 569 (1923). 

 6» S. Gabriel and J. Colman, Ber. 34, 1246 (1901); (\ O.Johns, Aw. Chvm. J. 41, 5S (190S). 



