Quantum Chemical Studies on the Reactivity of Electron-Rich Heterocycles: Benzofuroxans

Abstract

Quantum chemical methods enable the investigation of chemical reaction mechanisms and must be considered a powerful tool for gaining a detailed understanding of chemical reactivity. Their state-of-the-art applications, known as ‘computational chemistry’ or ‘molecular modeling’ have been successful in drug design, biotechnology, and many other areas. However, their application to electron-rich heterocycles is hampered by so-called electron-correlation effects. The dramatic developments in computer technology and recent progress concerning the efficiency of quantum chemical algorithms allow for the investigation of these compounds and their reactions. Still, the sensitivity of the electronic structure of these molecules make such a task a subject to high-performance computing. The molecular class off uroxans and benzofuroxans are known as ‘electron-overcrowded’ and could thus not be treated reliably by computational methods at low levels. An overview is presented here that mainly deals with molecular rearrangements of benzofuroxans and nitrobenzofuroxans. Although most of these reactions are known for a long time their detailed mechanisms could not be explained based only on experimental evidence or at least gave rise to repeated speculations about the basic steps of the actual reaction paths. The progress in understanding the reactivity of benzofuroxans by means of computing the transition states of their reaction mechanisms is summarized.

The vibrational spectra of furoxan and dichlorofuroxan: A comparative theoretical study using density functional theory and local electron correlation methods

“…This is a well-known failure of the MP2 method. 21 This demonstrates that the weak-pair approximation is safe for geometrical parameters of correlation sensitive molecules.…”

“…1), which are known to be extremely sensitive with respect to dynamical correlation effects. 21,22 The spectra of the similar compounds dibromofuroxan and diiodofuroxan have been studied recently. 23 For furoxan, an experimental spectrum was recorded from KBr pellets by Godovikova et al, 24 and thus the typical deviations from high quality FT-IR gas phase spectra are to be expected.…”

Dinitroso and polynitroso compounds

“…It was suggested earlier 125 that successful theoretical understanding of the benzofuroxan/o-dinitrosobenzene system is dependent upon the inclusion of electron correlation in the theoretical studies as illustrated by recent studies [50][51][52] of the reaction mechanisms of benzofuroxans in which o-dinitrosobenzenes feature as important intermediates. It seems likely that the differences between the results obtained from earlier computational studies of dinitrosoalkenes are a result of working at lower computational levels.…”

“…More recent studies of the molecular rearrangements of some substituted benzofuroxans have been made using different families of quantum chemical methods, in particular semi-empirical methods, density functional methods and ab initio methods. [50][51][52] These higher level calculations are applied to the ring opening reaction in benzofuroxans (see also Section 4). Interestingly, crystalline-state photolysis of 1-azido-2-nitrobenzene results in heterocycle formation to give the benzofuroxan which was identified by X-ray crystallography; 53 this result is in agreement with computational and pyrolysis studies.…”

“…It has been demonstrated 117 that theoretical calculations for dinitrosoalkenes and hence, by implication, for molecules (13) (14) containing two nitroso groups attached to p-bonded carbon frameworks, need to be performed at higher levels in order to to clarify the effects of linking the strong p-electron accepting nitroso groups to a conjugated system. It was suggested earlier 125 that successful theoretical understanding of the benzofuroxan/o-dinitrosobenzene system is dependent upon the inclusion of electron correlation in the theoretical studies as illustrated by recent studies [50][51][52] of the reaction mechanisms of benzofuroxans in which o-dinitrosobenzenes feature as important intermediates. It seems likely that the differences between the results obtained from earlier computational studies of dinitrosoalkenes are a result of working at lower computational levels.…”