title: Alternative Route Toward Nitrones: Experimental and Theoretical Findings.
abstract: Nitrones are important building blocks for natural and biologically active compounds, used as spin-trap reagents and therapeutic agents. All this makes nitrones intriguing and valuable compounds for fundamental studies and as useful chemicals in various synthetic strategies. Therefore, nitrones are still of great interest and in the limelight of researches. With our initial goal to solve synthetic problems toward 5-phenyl-2,2'-bipyridine (Phbpy), we found that this reaction can proceed through the formation of 6-phenyl-3-(pyridin-2-yl)-1,2,4-triazin-4(3H)-ol (4-OH), which rapidly isomerizes to a 3,4-dihydro-1,2,4-triazine-based nitrone, namely 6-phenyl-3-pyridin-2-yl-2,3-dihydro-1,2,4-triazin-4-oxide (4'), This encouraged us to study condensation of hydrazonophenylacetaldehyde oxime (2), obtained from 2-isonitrosoacetophenone (1), with other aldehydes. The reaction with both salicylaldehyde and p-tolualdehyde leads to the open-chain isomers, namely (2-hydroxybenzylidene)hydrazono-2-phenylacetaldehyde oxime (5) and (4-methylbenzylidene)hydrazono-2-phenylacetaldehyde oxime (6), respectively. The latter product exists in solution in equilibrium with its cyclic isomer 6-phenyl-3-(4-methylphenyl)-2,3-dihydro-1,2,4-triazin-4-oxide (6'), while the former one exists in solution exclusively in the open-chain form. It was also found that 2 reacts with acetone with the formation of 3,3-dimethyl-6-phenyl-2,3-dihydro-1,2,4-triazin-4-oxide (7'), which also exists in solution in equilibrium with its open-chain isomer 2-phenyl-2-(propan-2-ylidenehydrazono)acetaldehyde oxime (7). The static DFT as well as ab initio molecular dynamics simulations have corroborated the experimental findings.
authors.affiliation: Institute of Condensed Matter and Nanosciences, Molecules, Solids and Reactivity (IMCN/MOST), Université catholique de Louvain , Place L. Pasteur 1, 1348 Louvain-la-Neuve, Belgium.
authors.forename: Damir A
authors.identifier: 0000-0002-9080-7072
authors.initials: DA
authors.lastname: Safin
authors.affiliation: Department of Theoretical Chemistry, Faculty of Chemistry, Jagiellonian University , R. Ingardena 3, 30-060 Cracow, Poland.
authors.forename: Mariusz P
authors.identifier: 0000-0001-5359-9107
authors.initials: MP
authors.lastname: Mitoraj
authors.affiliation: Institute of Condensed Matter and Nanosciences, Molecules, Solids and Reactivity (IMCN/MOST), Université catholique de Louvain , Place L. Pasteur 1, 1348 Louvain-la-Neuve, Belgium.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Babashkina
authors.affiliation: Department of Theoretical Chemistry, Faculty of Chemistry, Jagiellonian University , R. Ingardena 3, 30-060 Cracow, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Kubisiak
authors.affiliation: Institute of Condensed Matter and Nanosciences, Molecules, Solids and Reactivity (IMCN/MOST), Université catholique de Louvain , Place L. Pasteur 1, 1348 Louvain-la-Neuve, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Robeyns
authors.affiliation: Institute of Condensed Matter and Nanosciences, Molecules, Solids and Reactivity (IMCN/MOST), Université catholique de Louvain , Place L. Pasteur 1, 1348 Louvain-la-Neuve, Belgium.
authors.forename: Yaroslav
authors.initials: Y
authors.lastname: Filinchuk