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

Abstract

The condensation of 2-benzimidazolamine (4, BIA) with α,β-unsaturated ketones 1 affords, according to Desenko, Orlov et al. [12,13], 1,4-dihydropyrimido[1,2-a]benzimidazoles (1,4-DHPBI, 51). However, the described ring closure reactions could a priori also yield isomeric 1,2-DHPBI 81 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·HCl were generated. In DMSO-d6 these isomers exclusively exist as 1,4-dihydro tautomers 5a,eI and 5a,eI·HCl. In trifluoroacetic acid 3,4-dihydro tautomers 5a,eIII-CF3COOH besides of tautomers 5a,eI·CF3COOH (≈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 α,β-unsaturated ketones 1b-d and f yielded 1,4-DHPBI 5b-dI and 5fI and their hydrochlorides, respectively The stereochemistry of bases 5a,eI, of salts 5a-eI-HCl 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.