Intramolecular noncovalent C-bonding driven conformational preference in spiroisatin-based -acyl hydrazones.

Noncovalent carbon bonding (C-bonding), a recently explored σ-hole interaction, has primarily been characterized through X-ray structural and computational studies. Evidence of C-bonds in solution is scarce, especially in highly polar solvents like DMSO where solvation effects typically overshadow weak non-covalent interactions. In this work, we present three novel spiroisatin-based -acyl hydrazones (1-3) in which C-bonds play a critical role in stabilizing the conformation in solution. Despite the steric preference for the NH-amide bond to adopt the geometry (H-N-C[double bond, length as m-dash]O ≈ 180°), H and C NMR spectra of compounds 1 and 2 in DMSO- reveal a rotameric mixture with a higher percentage of the conformation (82% and 76%, respectively), attributed to the stability provided by intramolecular C-bonding. Compound 3 also predominantly adopts the conformation in DMSO but to a lesser extent (60%) than compounds 1 and 2, due to competing intramolecular hydrogen bonding. Single-crystal X-ray analysis of compounds 1 and 2 confirmed the conformation, consistent with the solution-state preference. In contrast, compound 3 crystallized in the form, likely due to intramolecular hydrogen bonding and solid-state packing effects, which reinforce the steric preference for the geometry. Density functional theory (DFT) calculations corroborated the experimental data, predicting greater stability for the conformations in compounds 1, 2, and 3 in solution. The ability of intramolecular C-bonding to stabilize the conformation, even in highly polar solvents like DMSO, highlights the broader significance of this interaction in supramolecular chemistry and related fields.