Catalyst-Free One-Pot Access to Pyrazoles and Disulfide-Tethered Pyrazoles via Deamidative Heteroannulation of β-Ketodithioesters with Semicarbazide Hydrochloride in Water

Abstract

An operationally simple, mild, and catalyst-free one-pot protocol to access privileged pyrazoles and disulfide-tethered pyrazoles has been devised by [3+2] heteroannulation of β-ketodithioesters with semicarbazide hydrochloride in water under open air. The pH of the medium played a key role toward the selectivity switch, as refluxing in water led to the formation of pyrazoles, whereas addition of sodium acetate in water enabled the formation of disulfide-tethered pyrazoles. Notably, this protocol involves a tandem sequence of amination/cyclization/dehydration/hydrodesufurization/hydrolysis/deamidative reactions. A mechanistic rationale for this regio-/chemoselective domino reaction is outlined, which is well supported and validated by density functional theory calculations. (Figure presented.). © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim