Franco Vairoletti, Paulina Rodríguez, Jorge Cantero, Margot Paulino, Natalia Alvarez, Javier Ellena, Gustavo Salinas, Gonzalo Hernández Dossi, Graciela Mahler, Cecilia Saiz,
Benzamides have been recently introduced in the market as nematicides, representing a new family of compounds against plant-parasitic nematodes. In this context, the present work describes the design, synthesis and structural characterization of new N-alkyl benzamides and its evaluation as nematicidal compounds. The prepared compounds presented cis/trans isomerism in solution, observed at the 1H NMR spectra in CDCl3 and DMSO-d6. In order to assign each isomer signals, we performed different experiments supported by in silico studies. The identification of each isomer in the 1H-NMR spectra was performed based on theoretical DFT calculations using 1H-NMR prediction. For F-containing compounds, 19F-NMR prediction, conformational analysis and experimental 1H-19F COSY confirmed the results. Among the studied compounds, terminal N-methyl cis isomers displayed higher, experimental and calculated, 1H-NMR shifts, compared to the trans ones. Conversely, for the corresponding 13C-NMR signals, higher chemical shifts were observed for the trans isomers compared to the cis ones.The compounds structure 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 C. elegans. Among the N-alkylated benzamides, N-methyl-thioamide 10 showed the highest motility inhibition (56 ± 4 % at 10 μM).
https://doi.org/10.2139/ssrn.6315400
@article{Vairoletti_2026, title={An integrated NMR and DFT study on the conformational preferences of N-alkyl benzamides}, url={http://dx.doi.org/10.2139/ssrn.6315400}, DOI={10.2139/ssrn.6315400}, publisher={Elsevier BV}, author={Vairoletti, Franco and Rodríguez, Paulina and Cantero, Jorge and Paulino, Margot and Alvarez, Natalia and Ellena, Javier and Salinas, Gustavo and Hernández Dossi, Gonzalo and Mahler, Graciela and Saiz, Cecilia}, year={2026} }