N-aryl hydroxamic acids, which are best-known for their metal-chelating and extracting properties in chemical and biomedical research, have been found to markedly detoxify carcinogenic halogenated quinones. However, the exact chemical mechanism underlying such detoxication remains not clear. Here we show that N-phenylbenzohydroxamic acid (N-PhBHA) could readily react with 2,5-dichloro-1,4-benzoquinone (DCBQ) to form an unexpected new carbon-carbon bonding compound CBQ(OH)-PhBA (N-(3'-chloro-6'-hydroxy-2',5'-dioxo-2',5'-dihydro-[1,1'-biphenyl]-2-yl)benzamide) (96% yield), which is the isomer of the DCBQ O-activated N-PhBHA intermediate CBQ-O-N-PhBHA. In contrast, no reaction was observed with O-benzoyl N-PhBHA. Analogous effects were observed for other N-aryl hydroxamic acids and halogenated quinones which have an O-hydrogen adjacent to the reaction site (DCBQ-type). Interestingly, no free radical intermediates could be detected by ESR spin-trapping and radical scavenging methods. On the basis of these data, we proposed that nucleophilic substitution followed by an unprecedented Claisen rearrangement reaction was responsible for the formation of new C-C bonding compound and the detoxication reaction. This represents the first report of an unusually mild and facile Claisen-type rearrangement, which could take place under normal physiological conditions.

Unprecedented Claisen rearrangement reaction under normal physiological conditions

256th National Meeting (2018)

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