Studies of tautomerism and protonation in 2-aryl-1H-imidazo[1,2-a]imidazole derivatives using 1H and 13C NMR

✍ Scribed by Maili Liu; R. Duncan Farrant; Robert C. Glen; John C. Lindon; Paul Barraclough; Steven Smith

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 459 KB
• Volume: 29
• Category: Article
• ISSN: 0749-1581
• DOI: 10.1002/mrc.1260291112

✦ Synopsis

Abstract

The tautomerism and protonation of the putative inotropic 2‐(2′,4′‐dimethoxy)phenyl‐1__H__‐imidazo[1,2‐a]imidazole (2) has been studied in several solvents by comparing its ^1^H and ^13^C 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 1__H__‐tautomer in CDCl~3~, but as the 7__H__‐tautomer in DMSO‐d~6~ and methanol‐d~4~–D~2~O solutions. In CDCl~3~ solution, 2 appears to exist with the N‐1‐H and 2′‐OMe groups adjacent, but in DMSO‐d~6~ the conformation is the rotated form with N‐7‐H and H‐6′ adjacent; 3 exists as a mixture of rotamers in CDCl~3~ and in DMSO‐d~6~ 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‐d~6~ and at N‐7 in CDCl~3~, as expected from observed tautomeric ratios in the free base.