Title: An integrated NMR and DFT study on the conformational preferences of N-alkyl benzamides
Abstract: Recently introduced to the market, benzamides represent a new chemical family for combating plant-parasitic nematodes. This work describes the design, synthesis and structural characterization of novel N-alkyl benzamides and evaluates their efficacy as nematicides.The prepared compounds presented cis/trans isomerism in solution, as evidenced by 1H-NMR spectra in CDCl3 and DMSO‑d6. Isomer assignment was achieved using a combination of experimental data and density functional theory (DFT) calculations, including 1H-NMR chemical shift predictions. For F-containing compounds, 19F-NMR predictions, conformational analysis and 1H-19F COSY experiments provided additional support. Among the studied compounds, terminal N-methyl cis isomers displayed higher 1H-NMR chemical shifts than the corresponding trans isomers, whereas 13C-NMR signals presented higher chemical shifts for the trans isomers compared to the cis ones.One of the compound's structures was further characterized in the solid state. Pyridine N-methylamide 7 yielded suitable crystals for X-ray diffraction of the trans isomer. The intermolecular interactions observed included non-classical C–H···O and C–H···F hydrogen bonds as well as a 4% contribution of Cl···F interactions. Infrared spectrum for 7 was analyzed and signals assigned with the aid of computational tools. All compounds were assayed against Caenorhabditis elegans. Among the N-alkylated benzamides, N-methyl-thioamide 10 showed the highest motility inhibition (56 ± 4% at 10 μM).
