10.1021/jo5022713
The study investigates the unusual molecular mechanism of the Lossen rearrangement reaction activated by carcinogenic halogenated quinones. It explores how chlorinated benzoquinones (CnBQ) serve as new activating agents for benzohydroxamic acid (BHA), leading to the Lossen rearrangement. The chemicals involved include various chlorinated benzoquinones (such as TCBQ, 2,5-DCBQ, 2,6-DCBQ, 2-CBQ, and TrCBQ), benzohydroxamic acid (BHA), phenyl isocyanate (Ph-NCO), and N,N′-diphenylurea. The study finds that the stability of CnBQ-activated BHA intermediates depends on both the degree and position of Cl-substitution on CnBQs, which can be divided into two subgroups based on their stability. The rate of the CnBQ-activated rearrangement is determined by the relative energy of the anionic CnBQ?BHA intermediates, with the Cl or H ortho to the reaction site at CnBQ being crucial for the stability of these intermediates. A pKa?activation energy correlation is observed, linking the rate of rearrangement to the acidity of the conjugate acid of the anionic leaving group. The study combines experimental and computational methods to provide insights into this novel halogenated quinone-activated Lossen rearrangement, which has implications for understanding the detoxification of carcinogenic quinones and the potential biomedical applications of hydroxamic acids.
