Studies of Tautomerism and Protonation in 2-Aryl-1H-imidazoimidazole Derivatives Using 1H and 13C NMR

Article abstract of DOI:10.1002/mrc.1260291112

The tautomerism and protonation of the putative inotropic 2-(2',4'-dimethoxy)phenyl-1H-imidazo<1,2-a>imidazole (2) has been studied in several solvents by comparing its 1H and 13C chemical shifts with those of its 1- and 7-methyl derivatives 3 and 4, respectively, and acid salts.Tautomer and rotamer populations were also estimated from measurements of proton relaxation rates and NOE effects.Heterocycle 2 exists predominantly as the 1H-tautomer in CDCl3, but as the 7H-tautomer in DMSO-d6 and methanol-d4-D2O solutions.In CDCl3 solution, 2 appears to exist with N-1-H and 2'-OMe groups adjacent, but in DMSO-d6 the conformation is the rotated form with N-7-H and H-6' adjacent; 3 exists as a mixture of rotamers in CDCl3 and in DMSO-d6 whereas 4 is in the form with the N-7-Me and H-6' adjacent in both solvents.The observed conformational preferences have been compared with the results of semi-empirical molecular orbital calculations and found to be in broad agreement.Protonation of 2 occurs mainly at N-1 in DMSO-d6 and at N-7 in CDCl3, as expected from observed tautomeric ratios in the free base. KEY WORDS Protonation, Tautomerism, NMR, Imidazo<1,2-a>imidazole