Synthesis of (E)-4,5-Dihydro-1H-Pyrazoles via Tandem Intermolecular Addition–Cyclization of N-Propargylic Sulfonylhydrazones

Abstract

A new strategy for the synthesis of (E)-4-benzylidene-4,5-dihydro-1H-pyrazoles through tandem intermolecular addition–intramolecular cyclization of N-propargylic sulfonylhydrazones has been developed. In this study, we firstly report that N-propargylic sulfonylhydrazones react with electrophilic reagents to afford 4-substituted pyrazole derivatives.

Key words

propargyl hydrazones - dihydropyrazoles - acetals - intermolecular reaction

• References and Notes

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• 14 Representative Procedure for the Preparation of (E)-4-Benzylidene-4,5-dihydro-1H-pyrazoles 2 To a solution of N-propargylic sulfonylhydrazone 1 (0.5 mmol) and acetals 3 (1 mmol) in DBE (5 mL), FeCl₃ (0.1 mmol) was added, and the mixture was stirred at 80 °C. When the reaction was completed (monitored by TLC), water was added to the mixture. The aqueous phase was extracted with CH₂Cl₂ (3 × 10 mL). The combined organic layers were washed with brine and dried over Na₂SO₄. The solvent was removed under vacuum, and then the residue was further purified by silica gel column chromatography (PE and EtOAc) to afford product 2.
• 15 Representative Analytical Data of (E)-4-Benzylidene-3-phenyl-1-tosyl-4,5-dihydro-1H-pyrazole (2a) White solid (mp 149–150 °C). ¹H NMR (500 MHz, CDCl₃): δ = 2.43 (s, 3 H), 4.81 (s, 2 H), 6.74–6.80 (m, 1 H), 7.25 (d, 2 H, J = 7.3 Hz), 7.32–7.38 (m, 3 H), 7.41–7.52 (m, 5 H), 7.60 (d, 2 H, J = 7.1 Hz), 7.88(d, 2 H, J = 8.0 Hz). ¹³C NMR (125 MHz, CDCl₃): δ = 21.6, 54.2, 126.3, 128.6, 128.7, 128.8, 128.8, 128.9, 129.7, 129.8, 130.1, 132.0, 133.9, 135.3, 144.5, 160.1. ESI-HRMS: m/z calcd for C₂₃H₂₀N₂O₂S [M + H]⁺: 389.1318; found: 389.1322.