Synthese von Pyrimido[1,2‐ a ]benzimidazolen durch Umsetzung von 2‐Aminobenzimidazol mit Acetylendicarbonsäure‐dimethylester und ihre Überführung in Imidazo[1,2‐ a ]benzimidazole

The main product of the reaction between 2‐aminobenzimidazole and dimethyl acetylenedicarboxylate is shown to be methyl 1, 2‐dihydro‐2‐oxo‐pyrimido[1, 2‐ a ]benzimidazole‐4‐carboxylate ( 6 ), which can be methylated at position 1 to give 7 . Catalytic hydrogenation of 7 leads to the 1,2,3,4‐tetrahydro derivative 8 , whereas NaBH 4 reduces the ester and, to some extent, the double bond to yield a mixture of 9 and 10 . When a 1‐substituted 1, 2‐dihydro‐4‐hydroxymethyl‐pyrimido[1, 2‐ a ]benzimidazol‐2‐one (for example 11 ) is catalytically hydrogenated, the double bond is unaffected, but hydrogenolysis of the alcohol group occurs instead to give 13 . The lactam group is less stable in the tetrahydro series than in the dihydro compounds. For example, the lactam is cleaved when 8 is treated with amines containing a small amount of water, and the monoamides 16 and 17 are formed. Similarly, sodium hydroxyde cleaves the lactam under mild conditions to the dicarboxylic acid 19 , which can be converted to 2, 3‐dihydro‐1‐methyl‐2‐oxo [1 H ]imidazo[1, 2‐ a ]benzimidazole‐3‐acetic acid (4‐methyl)piperazide ( 20 ) with thionyl chloride and N‐methylpiperazine. However, when 7 is treated with methylamine at low temperature, the amide 22 is formed, whilst at room temperature the amine attacks both the ester and the double bond to give 23 . The structure of 8 was confirmed by X‐ray analysis.