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

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.