III. INDUSTRIAL PREPARATION 417 



2-Methyl-4-aminopyrimidyl[5]carbonic acid is formed''' \\ith a yield of 

 65 to 75 %. By transformation of the carbethoxy group to the amide and 

 eyano group the way to the diamine is opened. It is remarkable that the 

 neutral or acid ring closure goes so well. The drawback of the method is the 

 low yield in the formation of the acrylic acid (40%, see above). 



The best manner of the ring closure with direct introduction of the amino 

 group was first described by Grewe.'" When the alcoholic solutions of free 

 acetamidino and ethoxymethylenc malonitrile are united, the mixture 

 solidifies at once under formation lof the crystalline cyano compound. 



XHo CX N=C— NH, 



CH3— C + C— CN -» CH3— C C— CN 



NH CHOEt N— CH 



Grewe himself gi\'es no yield; in the laboratories of Elberfeld*^ a yield of 

 69 % was obtained. 



Ethoxymethylene malonitrile can be cjuantitatively converted to amino- 

 methylene malonitrile;-^' the condensation with acetimino eihy\ ether gives 

 the l)est yield for the pyrimidine ring closiu'e reported in literature,-' 



NH CN N=C— NH2 



II I II 



CH3— C + C— CN -^ CH3— C C— CN + Eton 



I II II II 



OEt HoN— CH N— CH 



namely 88 %. The resulting 2-methyl-4-amino-5-cyanopyrimidine was 

 catalytically hydrogenated by Grewe'" with palladium charcoal as a catalyst 

 and glacial acetic acid with dry hydrogen chloride as a solvent. No yield is 

 given by Grewe, but it can be assumed fi'om similar hydrogenations of 

 nitriles that it is very good. 



Glacial acetic acid in the presence of hydrogen chloride is not a very 

 pleasant medium for high-pressure hydrogenation as it corrodes even 

 normally acid-resistant metals considerably. The difficulty can be overcome 

 by specially constructed autoclaves. 



4. Group C, Five Carbon Atoms for the Thiazole Ring 



The possibilities for the synthesis of the thiazole ring are nearly as 

 numerous as those of the pyrimidine ring, and the different groups in the 

 three countries together with industiial laboratoi'ies have de\-eloped more 

 than half a dozen ways for the five carbon atoms. 



35 Chinoin, Budapest, Rritish Pat. 538,743 (August 14, 1941). 



" I. G. Farben, Werk Elberfeld, technical directions for Bi, as of Jul}- 1, 1943. Micro- 

 film FD 20/46, Docket No. 63,986. H. M. Stationary Office, Photogr. Section. 



