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Studies of tautomerism and protonation in 2‐aryl‐1 H ‐imidazo[1,2‐ a ]imidazole derivatives using 1 H and 13 C NMR
Author(s) -
Liu Maili,
Farrant R. Duncan,
Glen Robert C.,
Lindon John C.,
Barraclough Paul,
Smith Steven
Publication year - 1991
Publication title -
magnetic resonance in chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.483
H-Index - 72
eISSN - 1097-458X
pISSN - 0749-1581
DOI - 10.1002/mrc.1260291112
Subject(s) - tautomer , chemistry , protonation , conformational isomerism , imidazole , hydrogen bond , aryl , chemical shift , stereochemistry , medicinal chemistry , crystallography , computational chemistry , molecule , organic chemistry , alkyl , ion
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.