Synthesis and structural elucidation of pyrimido[1,2-a]benzimidazoles and fused derivatives .1. Dihydropyrimido[1,2-a]benzimidazoles

The condensation of 2-benzimidazolamine (4, BIA) with alpha,beta-unsaturated ketones 1 affords, according to Desenko, Orlov et al. [12,13], 1,4-dihydropyrimido[1,2-a]benzimidazoles (1,4-DHPBI, 5I). However, the described ring closure reactions could a priori also yield isomeric 1,2-DHPBI 8I or tautomers of DHPBIs 5I and 8I. An unequivocal proof for the postulated structures 5I was not presented. We prepared, as described [12,13], BIA-chalcone- and BIA-benzalacetone-condensate X and Y, 5a,e or 8a,e, and additionally, their hydrochlorides. One and two dimensional high resolution nmr analyses showed that only isomers 5a,e and salts 5a,e . HCI were generated. In DMSO-d(6) these isomers exclusively exist as 1,4-dihydro tautomers 5a,eI and 5a,eI . HCI. In trifluoroacetic acid 3,4-dihydro tautomers 5a,eIII . CF3COOH besides of tautomers 5a,eI . CF3COOH (approximate to 1:4) were ascertained. Action of ethanolic hydrochloric acid on base 5eI afforded, besides of 5eI . HCl as main product; a small amount of 2-methyl-4-phenyltetrahydropyrim-ido[1,2-a]benzimidazol-2-ol hydrochloride 9e . HCl. The reaction of BIA 4 with alpha,beta-unsaturated ketones 1b-d and f yielded 1,4-DHPBI 5b-dI and 5fl and their hydrochlorides, respectively. The stereochemistry of bases 5a,eI, of salts 5a-eI . HCI and 5a,eIII . CF3COOH, and of addition product 9e . HCl was elucidated by nmr (stereoformulae in Figures 1-3 and Scheme 5). The accomplished nmr-analyses are documented in detail and discussed.