Abstract
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-N-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.
Highlights
Michael addition followed by a Nef-type rearrangement reaction (Scheme 1) in which coumarin derivatives 1 are transformed into pyrrolidinedione products 8, 1-hydroxy-4-(2-hydroxyphenyl)-2,5-dioxopyrrolidine was reported to occur with an excellent yield.[1,2]
In the current study we aim at elucidating the reaction mechanism by means of quantum chemical modelling based on density functional theory (DFT) and Møller–Plesset perturbation theory of second order (MP2) on the example of the coumarin transformation under the reaction conditions
Nef-type rearrangement of the nitromethyl group to nitroso-hydroxymethyl group including tautomerization of the nitromethyl group to aci-nitromethyl followed by oxygen migration from N to C atom (Fig. 2–4); 2.3
Summary
Michael addition followed by a Nef-type rearrangement reaction (Scheme 1) in which coumarin derivatives 1 are transformed into pyrrolidinedione products 8, 1-hydroxy-4-(2-hydroxyphenyl)-2,5-dioxopyrrolidine was reported to occur with an excellent yield.[1,2] Initially the reaction was reported with 3-phosphonocoumarin, but later we showed that this rearrangement reaction occurs with other 3-substituted coumarins and the coumarin itself as reactants 2 and can nd application in the target synthesis of 3,4-disubstituted pyrrolidine derivatives with potential biological activity. Khrapkovskii et al.[21] showed that the activation energy for formation of the nitromethane aci-forms is 317.8 (319.4) kJ molÀ1 at MP3/ RHF(DZV-1d) (CCD/RHF(DZV-1d)) in good agreement with the results of Bock et al.,[19] and the reaction is endothermic by 69.5 (71.8) kJ molÀ1 These model studies concern the initial tautomerization of nitromethane but the Nef rearrangement mechanism via protonation of the aci-nitro intermediate or via formation of oxaziridine ring has not been modelled so far by computational methods. By this reason, we modelled the Nef rearrangement in various ways as a component of the entire. Paper process of 3-nitromethyl coumarin transformation into pyrrolidinedione derivative
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