ANEURINE (thiamine) 



ester. This gave the 5-carboxylic ester which was converted to the 

 corresponding amide, and thence to the nitrile. 



The use of potassium dithioformate was patented by Hoffmann- 

 La Roche/2 who also patented a number of other reactions enabling 

 them to synthesise aneurine by a unique process which was used for 

 its large-scale manufacture. The requisite pyrimidine compounds 

 were synthesised ^^ from acetimino-ethyl ether hydrochloride and 

 aminomethylene malondinitrile, the preparation of the latter being 

 described in a later patent.^* 



OC2H5 NHa— CH N=CH 



I II II 

 CH3 . C + C . CN > CH3 . C C . CN 



II I II II 



NH CN N— C . NHa 



The product was reduced, as in Todd's process, to the aminomethyl 

 compound, which was then converted ^^ by treatment with potassium 

 dithioformate into the thioformamidom ethyl derivative. This was 

 treated,^^ not with 3-aceto-3-halogenopropyl alcohols or their esters, 

 but with 3-chloro-2-ethoxy-2-methyl-tetrahydrofurane to yield aneu- 

 rine. The relation between the two types of compound is evident 

 from the following formulae : 



CI . CH— CHa CI . CH— CH2 



II II 



CH3— C CH2 CH3.CO CH2 



/ 



.H.O O 



OH 



The preparation of this furane derivative, due to Klingenfuss, was 

 covered in another patent. ^^ A variant of this process, due to 

 Chinoin,^^" comprises the treatment of 2 : 3-dihalogeno-2-methyl-tetra- 

 hydrofurane with an agent capable of removing hydrogen chloride and 

 then condensing the product with the thioformamidomethyl compound. 

 The constitution of halogenated acetopropyl alcohols has been the 

 subject of extensive investigation, and J. R. Stevens and G. A. Stein^^ 

 showed that halogenated acetopropyl alcohols, more especially the 

 bromo-derivative, exist in the form of a dimeride of the formula : 



/CH, 

 CH2 C< 



\ / \0 . CHa . CHa . CHCl . CO . CHj 

 O 



It is thus the acetochloropropyl ether of 3-chloro-i-hydroxy- 

 i-methyl-tetrahydrofurane. The preparation of this compound has 

 been patented.^® 



18 



