Tautomerism troubles: proton transfer modifies the stereochemical assignments in diastereoisomeric structures of spirocyclic 5-methyl-2H-imidazol-4-amine dimers

Abstract

During the racemization of a novel pharmaceutical spirocyclic imidazole–amine compound, namely, 6′-bromo-N-(6′-bromo-4-methoxy-4′′-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2′′-imidazol]-5′′-yl)-4-methoxy-4′′-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2′′-imidazol]-5′′-imine, C36H41Br2N5O2, two impurities were isolated. These impurities were clearly dimers from mass spectroscopic analysis, however single-crystal diffraction characterization was required for the assignment of stereochemistry. The single-crystal diffraction results revealed subtly different structures to those proposed, due to an unexpected proton transfer. The dimers contain four stereocentres, but two of primary interest, and are centrosymmetric, so after careful structure refinement and close inspection it was possible to unambiguously assign the stereochemistry of both the homochiral [(S),(S)- and (R),(R)-] and the heterochiral [(S),(R)- and (R),(S)-] compounds.

Keywords

• chirality assignment
• pharmaceutical
• crystal structure