An unusual semiquinone-mediated self-catalysis redox mechanism for the reaction between halohydroquinones and N-substituted hydroxamic acids

Abstract

We found recently that a C-C bonding phenyl-quinone product was produced with high yield (96 %) from the reaction between 2,5-dichloro-1,4-benzoquinone (DCBQ) and N-phenylbenzohydroxamic acid (N-PhBHA) via an unusual Claisen rearrangement mechanism, accompanied with the concurrent formation of the minor byproducts amide (N-phenylbenzamide, N-PhBA; only 2 % yield) and hydroxychloroquinone (2 % yield). Surprisingly, when DCBQ was replaced with its reduced form 2,5-dichloro-1,4-hydroquinone (DCHQ), no C-C bonding product was detected, whereas N-PhBA (83 % yield) and hydroxychloroquinone (80 % yield) became the predominant products, indicating a dramatic mechanistic shift. The ascorbate reduction experiment suggested that it was not DCHQ itself, but its corresponding semiquinone radical, that directly reacts with N-PhBHA. Analogous results were observed when N-PhBHA was substituted with its N-methylated analog (N-methyl Benzohydroxamic acid, N-MeBHA), and when DCHQ was replaced with other halohydroquinones. Taking advantage of the relative stability of the N-MeBHA-quinone conjugate intermediate, we demonstrated that this quinone conjugate was capable of being reduced to its semiquinone form by DCHQ. Taken together, we proposed an unusual semiquinone-mediated self-catalysis redox mechanism for the reaction between halohydroquinones and N-substituted hydroxamic acids.