ANEURINE (thiamine) 



The formula now known to be correct : 



N=C— NH; CH3 



I i /C=C— CH2— CH2OH 

 CH3— C C— CH2 N<; I 



II II ^,Vh_s 



N— CH ^^ • HCl 



and subsequently proposed by R. R. Williams/^ takes into account 

 the revised formula for the pyrimidine half. The point of attachment 

 to the pyrimidine ring was settled by the position of the sulphonic 

 group in the sulphite cleavage product, whilst the point of attachment 

 to the thiazole ring was established by titration experiments. 



When aneurine chloride was titrated with alkali/* one mole was 

 taken up in a normal manner and therefore the pJi failed to increase, 

 except transitorily, almost immediately recovering its former value. 

 This continued until a total of three moles of alkali had been added 

 when a steady rise in pH occurred. This curious and unexpected 

 behaviour was interpreted to indicate an intramolecular rearrangement. 

 It was found ^^ that 5-/S-hydroxyethyl-4-methyl-thiazole methiodide 

 behaved similarly on titration, whence it was concluded that aneurine 

 chloride was also a quaternary ammonium salt. The explanation of 

 the titration results is that the thiazole ring is opened according to the 

 following series of changes : 



CH2— P CH2— P CHa— P CH2— P 



I I II 



CI . N C— HO . N C— N C— N C— 



II II -- > II II — I II -- > I II 

 CH C— CH C— HO-CH C— CHO C— 



\ 



S S S SH 



(where P = the pyrimidine ring). The third molecule of sodium 

 hydroxide is required to neutralise the mercapto group. 



References to Section 3 



1. R. R. Williams, " Vitamin Bj and its use in Medicine," Macmillan, 



1938. 



2. R. R. Williams, /. Amer. Chem. Soc, 1935, 57, 229 ; R. R. Williams, 



R. E. Waterman, J. C. Keresztesy and E. R. Buchman, ibid., 

 536. 



3. R. R. Williams, E. R. Buchman and A. E. Ruehle, ibid., 



1093. 



4. R. R. Williams, ibid., 1936, 58, 1063 ; J. K. Cline, R. R. Williams, 



A. E. Ruehle and R. E. Waterman, ibid., 1937, 59, 530. 



5. R. R. Williams, A. E. Ruehle and J. Finkelstein, ibid., 526. 



14 



