Conformational Analysis of Novel Benzene-1,3-Disulfonamide-Based Cycloalkynes Through X-Ray Crystallography, DFT Calculations, and NMR Spectroscopy.

Sulfonamides are a fundamental class of compounds with diverse pharmacological applications. Here, two benzene-1,3-disulfonamide-containing cycloalkyne compounds were designed to demonstrate the strained conformations due to the 11-membered ring. Their structures were experimentally analyzed using single-crystal X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy. The molecules exhibit flexible sulfonamide conformations together with characteristic distortions of the benzene and alkyne moieties. Comparing the compound data obtained, the proton NMR chemical shift of hydrogen at the 2-position of the benzene ring shows a correlation of a dihedral angle involving the benzene ring and sulfonamide sulfur, and the carbon NMR shift suggests an angle distortion of the alkyne. The conformations of the crystal structure and the solution state in DMSO are supported by NOESY spectra and DFT calculations. The relative chemical shift differences were quantitatively reproduced by DFT calculations. We believe this fundamental research will contribute to the design and development of sulfonamide-alkyne-benzene-based medium-sized heterocyclic molecules with detailed conformation predictions.