SYNTHESIS 



Roche Products patented the preparation of keto-alcohol acetates 

 such as 3-aceto-propyl acetate, by heating lactones, such as a-aceto- 

 y-butyrol acetone, with glacial acetic acid in presence of anhydrous 

 sodium acetate ^^ 



CH3.C00H 

 CH3 . CO . CH . CH2 . CHa ►CH3 . CO . CH2 . CH2 . CH2 . O . OC . CH, 



CO O 



though the conversion can be effected by means of sulphuric or phos- 

 phoric acid.20 The latter procedure can also be used for the forma- 

 tion of the 3-chloro- or 3-bromo-acetates. Roche Products also 

 protected the bromination of 3-acetopropyl acetate by the action of 

 sulphuryl chloride in presence of an alkali metal bromide at 60° C, 

 with silica as catalyst,^! and also 22 by reacting 3-acetopropyl alcohol or 

 its acetate with (a) a dibromide of a salt of pyridine or quinoline ; 

 (b) bromine and a salt of pyridine or quinoline ; and (c) chlorine, a 

 salt of pyridine or quinoline and an alkali metal bromide. The crude 

 products obtained from these reactions can be used for the preparation 

 of aneurine directly by condensation with 4-amino-2-methyl-5-thio- 

 formamidomethyl-pyTimidine.23 



The preparation of 5-alkoxymethyl-4-amino-2-methyl-pyrimidines 

 by reacting 4-amino-5-aminomethyl-2-methyl-pyrimi(iine with an 

 alkyl nitrite has also been patented. 2* 



German Method 



The methods of synthesis devised by the German workers are 

 described mainly in patent specifications. The first publication, 

 however, was a paper by R. Grewe ^s describing the condensation of 

 acetamidine with ethoxymethylene-malondinitrile to give 4-amino-5- 

 cyano-2-methyl-pyTimidine, which on hydrogenation with a palladium- 

 charcoal catalyst gave the corresponding 5-aminomethyl compound. 



NHa CN N^C.NHa N=C . NH^ 



CH3 . C + C . CN -> CH3 . C C . CN ^ CH3 . C C . CH2NH2 



II II II II II II 



NH C2H5O.CH N— CH N— CH 



He stated that Prof. Horlein had informed him that Andersag and 

 Westphal had already synthesised the vitamin in the laboratories of 

 the I.G.Farbenindustrie, and that as a result he had decided to abandon 

 his own investigations. A publication by H. Andersag and K. 

 Westphal ^e appeared in 1937 ; in this paper they described the 



19 



