biostudies-literatureUnknown8(6)Ilieva EDThis paper reports a quantum chemical study of all stages of a one-pot synthesis of pyrrolidinedione derivatives from nitromethane and coumarin, which includes Michael addition, migration of an oxygen atom (Nef-type rearrangement), and cyclization to a pyrrolidine ring. The energy barrier of deprotonated nitromethane addition to coumarin is 21.7 kJ mol^-1, while the barrier of proton transfer from the methylene to the nitro group in the nitromethyl group is notably higher, 197.8 kJ mol^-1. The second stage of the reaction, migration of an oxygen atom within the nitromethyl group, occurs with lowest energy barrier, 142.4 kJ mol^-1, when it is assisted by an additional water molecule. The last stage - cyclization, passes with a very low energy barrier of 11.9 kJ mol^-1 but the tautomerization of the nitrosohydroxymethyl group to the hydroxy-<i>N</i>-hydroxyiminomethyl, necessary for the process, has an energy barrier of 178.4 kJ mol^-1. Analogous calculations for the same process with the ethyl ester of 3-coumarin-carboxylic acid as substrate show that the relative energies of the intermediates and transition states are by at most 10-16 kJ mol^-1 more stable than the corresponding structures with coumarin.RSC advances3178-3188https://www.ebi.ac.uk/biostudies/studies/S-EPMC9077586biostudies-literatureComputational elucidation of the reaction mechanism for synthesis of pyrrolidinedione derivatives <i>via</i> Nef-type rearrangement - cyclization reaction.PMC9077586Ilieva EDVayssilov GNNikolova RDPetrova GPfalseComputational elucidation of the reaction mechanism for synthesis of pyrrolidinedione derivatives <i>via</i> Nef-type rearrangement - cyclization reaction.This paper reports a quantum chemical study of all stages of a one-pot synthesis of pyrrolidinedione derivatives from nitromethane and coumarin, which includes Michael addition, migration of an oxygen atom (Nef-type rearrangement), and cyclization to a pyrrolidine ring. The energy barrier of deprotonated nitromethane addition to coumarin is 21.7 kJ mol^-1, while the barrier of proton transfer from the methylene to the nitro group in the nitromethyl group is notably higher, 197.8 kJ mol^-1. The second stage of the reaction, migration of an oxygen atom within the nitromethyl group, occurs with lowest energy barrier, 142.4 kJ mol^-1, when it is assisted by an additional water molecule. The last stage - cyclization, passes with a very low energy barrier of 11.9 kJ mol^-1 but the tautomerization of the nitrosohydroxymethyl group to the hydroxy-<i>N</i>-hydroxyiminomethyl, necessary for the process, has an energy barrier of 178.4 kJ mol^-1. Analogous calculations for the same process with the ethyl ester of 3-coumarin-carboxylic acid as substrate show that the relative energies of the intermediates and transition states are by at most 10-16 kJ mol^-1 more stable than the corresponding structures with coumarin.2018-01-01T00:00:00Z2018 Jan2024-11-15T09:08:29.264Z2024-11-15T09:08:29.264ZS-EPMC90775863554118110.1039/c7ra11908a