Some kinetic and equilibrium studies of the reactions of nitrobenzofurazan derivatives with nucleophiles
The reactions of 4,6-dinitrobenzofuroxan, (DNBF) with aniline and six of its N- and ring- substituted derivatives have been studied. It is known that aniline usually reacts as a nitrogen nucleophile, forming nitrogen-bonded σ-adducts with trinitrobenzene, (TNB) in the presence of a strong base. However, in acidic solutions, a-adducts are formed with bonding between a ring carbon atom of the anilines and the 7-position of DNBF. A value of 2.0 for k(_H)/k(_D), the kinetic isotope effect, indicates that bond formation is largely rate determining in the substitution pathway. Estimates were made for the pK(_a) values relating to carbon protonation of the anilines. In solutions of aniline buffered with aniline hydrogen chloride it was possible to distinguish an initial, rapid reaction via the nitrogen centre to give anionic a-adducts. The thermodynamically more stable carbon-bonded σ-adducts were observed to form over time. In the presence of excess amine, these zwitterionic σ-adducts were in rapid equilibrium with the deprotonated forms. Equilibrium constants for this acid-base process were measured, and indicate that the negatively charged DNBF moiety is electron withdrawing relative to hydrogen. Kinetic and equilibrium studies are reported for the reactions of several aliphatic amines with a selection of nitrobenzofurazan derivatives in DMSO. Rapid reaction at the 5- position to yield σ-adducts was followed by slower formation of the thermodynamically more stable adducts at the 7-position. Proton transfer from the zwitterionic intermediates to a second molecule of amine was generally rapid, and the attack of the amine rate determining. This is in direct contrast with reactions involving TNB, where the proton transfer step is usually rate limiting. The reactions of four nitrobenzofurazan derivatives with sulfite have been studied in aqueous solutions. The stability of the initially formed 5-adducts was remarkably high in comparison with the corresponding σ-adducts formed from attack of sulfite on TNB. A slow isomerisation was observed to yield the thermodynamically more stable 7-adducts, except in the reaction with 4-nitro-7-chlorobenzofurazan, where attack at the 7-position would lead to nucleophilic substitution of the chloro-group to yield the substitution product. The mechanism of the isomerisation was found to occur via an intermolecular rearrangement, and not according to an intramolecular Boulton-Katritzky rearrangement. Sulfite attack on DNBF was also studied. A value for the equilibrium constant for the formation of a 1:1 adduct, K(_7) 1.1 x 10(^13) dm(^3) mol(^-1) was determined. This high value is a reflection of the high carbon basicity of the sulfite ion, and the highly electrophilic character of DNBF. Evidence was also obtained for the formation of 1:2 di-adducts in the presence of excess sulfite, which are present in the isomeric cis and trans forms.