What is it about?
In an attempt to synthesize a new 3H-benzo[b][1,4]diazepine derivative 3d with potential pharmaceutical activity, a substituted benzimidazole system 4d was unexpectedly obtained in the reaction of o-phenylenediamine with 2-benzoylcyclohexanone. Its structure was unambiguously determined by spectroscopic studies (IR, NMR, and MS) and single-crystal X-ray structural analysis. A closer analysis of the experimental 1H and especially 13C NMR spectra of the isolated product 4d monohydrate, analyzed in light of these data obtained theoretically for its two possible tautomers (DFT GIAO calculations), showed tautomeric exchange in the imidazole moiety.
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Why is it important?
The anhydrous form of the obtained title compound 4d was previously described in 2005 by Wang and Qin as a non-tautomerized benzimidazole system based on NMR spectra taken in dry CDCl3. Now, its hydrate was analyzed; therefore, the CDCl3 used contained traces of H2O. As is well known; see, for example, a recent review (Molecules, 2023, 28, 4369), wet CDCl3 usually contains traces of HCl, which strongly facilitates the occurrence of prototropic tautomeric equilibria in some molecular systems. As a result, both tautomeric forms of compound 4d were observed now in time-averaged 1H and especially 13C NMR spectra measured in wet CDCl3. Interestingly, due to compound 4d's highly specific nature, its molecular structure in solution involves two coexisting enantiomeric rotamers of equal energy. Only one tautomer is observed in the solid phase.
Perspectives
As seen from the example of compound 4d discussed here in more detail, obtaining products that one did not expect is not uncommon. This is the great beauty of chemical synthesis, especially of various organic molecular systems. Due to the ‘unpredictability’ of certain complex chemical processes, it is sometimes possible to discover completely new chemical systems, rearrangements, and/or much simpler pathways to systems already known. With the wide range of spectroscopic methods available today, especially 1D and 2D NMR spectra, supported by parallel calculations of these spectroscopic data at the DFT level, unambiguous determination of the structure of the resulting products or isolates is usually easy. Indeed, current NMR calculations of chemical shifts using the GIAO method have made it possible in recent years to structural reassignments of the chemical structure of many complex natural products, although NMR spectroscopy was widely used in their original, now proven erroneous identifications.
Associate Professor Ryszard Bolesław Nazarski
University of Lodz
Read the Original
This page is a summary of: Unexpected Formation of 6-(1H-Benzo[d]imidazol-2-yl)-1-phenyl-hexan-1-one and Its Structure in Solution and Solid State Analyzed in the Context of Tautomerism, Crystals, August 2024, MDPI AG,
DOI: 10.3390/cryst14080704.
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