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Updated: Oct 14, 2025

Efficient Synthesis of Polyfunctionalized Benzenes in Water via Persulfate-promoted Benzannulation of α,β-Unsaturated Compounds and Alkynes
Published on: December 16, 2019
Predictable site-selective functionalization: Promoter group assisted para-halogenation of N-substituted
Shiv Shankar Gupta1,2, Manisha1,2, Rakesh Kumar1,3
1Chemical Technology Division, CSIR-Institute of Himalayan Bioresource and Technology, Palampur 176061, India. upendra@ihbt.res.in.
Abstract:
Herein, regioselective para-C-H halogenation of N-pyrimidyl (hetero)aromatics through SEAr (electrophilic aromatic substitution) type reaction is disclosed. SEAr type reaction has been utilized for the C5-bromination of indolines (para-selective) with N-bromosuccinimide under metal and additive-free conditions in good to excellent yields. The developed methodology is also applicable for iodination and challenging chlorination. The pyrimidyl group is identified as a reactivity tuner that also controls the regioselectivity. The present method is also applicable for selective halogenation of aniline, pyridine, indole, oxindole, pyrazole, tetrahydroquinoline, isoquinoline, and carbazole. DFT studies such as Fukui nucleophilicity and natural charge maps also support the observed p-selectivity. Post-functionalization of the title compound into the corresponding arylated, olefinated, and dihalogenated products is achieved in a one-pot, two-step fashion. Late-stage C-H bromination was also executed on drug/natural molecules (harmine, etoricoxib, clonidine, and chlorzoxazone) to demonstrate the applicability of the developed protocol.
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