Automated Grindstone Chemistry: A Simple and Facile Way for PEG-assisted Stoichiometry-controlled Halogenation of Phenols and Anilines Using N-Halosuccinimide

Submitting author affiliation:
BITS Pilani KK Birla Goa Campus, South Goa, India

Beilstein Arch. 2022, 202249.

Published 13 Jun 2022

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A simple electrical mortar-pestle was used in the development of a green and facile mechanochemical route for the catalyst-free halogenation of phenols and anilines via liquid assisted grinding using PEG-400 as the grinding auxiliary. A series of mono-, di-, tri-halogenated phenols and anilines was synthesized in good to excellent yields within 10-15 min in a chemoselective manner by controlling the stoichiometry of N-halosuccinimide (NXS, X = Br, I, Cl). It was observed that PEG-400 plays a key role in controlling the reactivity of the substrates and to afford better regioselectivity. Almost exclusive para-selectivity was observed for the aromatic substrates with free o- and p-positions for mono- and di-halogenations. As known, the decarboxylation (or desulfonation) was observed in the case of salicylic acids, anthranilic acids (or sulfanilic acids) leading to 2,4,6-trihalogenated products when 3 equiv of NXS was used. Simple instrumentation, metal-free approach, cost-effectiveness, atom economy, short reaction time, and mild reaction conditions are a few noticeable merits of this environmentally sustainable mechanochemical protocol.

Keywords: mechanochemistry; automated grinding; stoichiometry-controlled halogenation; PEG-400; N-bromosuccinimide; regioselectivity; chemoselectivity

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Das, D.; Bhosle, A. A.; Chatterjee, A.; Banerjee, M. Beilstein Arch. 2022, 202249. doi:10.3762/bxiv.2022.49.v1

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