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DOI: 10.1055/s-2006-956487
Highly Regioselective Synthesis of 1-Aryl-3,4,5-Substituted Pyrazoles
Publication History
Publication Date:
23 November 2006 (online)
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Abstract
A highly regioselective synthesis of 1-aryl-3,4,5-substituted pyrazoles based on the condensation of 1,3-diketones with arylhydrazines is described. The reaction proceeds at room temperature in N,N-dimethylacetamide and furnishes pyrazoles in 59-98% yields.
Key words
1,3-diketones - arylhydrazines - cyclocondensation - regioselectivity - amide solvents
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References and Notes
Pyrazoles obtained by condensation of arylhydrazine hydrochloride salts with 1,3-diketones often gave isolable solvates of DMAc that could be broken to give pyrazoles by simple recrystallization from i-PrOH-H2O.
10Representative Procedure: To a solution of 4,4,4-trifluoro-1-(4-bromophenyl)butane-1,3-dione (1b; 1.47 g, 5 mmol) in N,N-dimethylacetamide (20 mL) at r.t. was added phenylhydrazine hydrochloride (723 mg, 5 mmol), followed by 10 N HCl (250 µL, 50 mol%). The mixture was let to stir for 24 h at r.t., cooled to 0 °C and H2O (20 mL) was slowly added. After diluting with toluene (30 mL), the organic layer was washed with H2O (3 × 20 mL) and concentrated to a brown oil that crystallized. The crystals were washed with cold heptane (3 × 5 mL) to give phenyl-3-(trifluoromethyl)-5-(4-bromophenyl)-1H-pyrazole(2j) as colorless crystals; yield: 1.36 g (74%); mp 103.7-105.4 °C. 1H NMR (500 MHz, CDCl3): δ = 7.44 (d, J = 7.4 Hz, 2 H), 7.36 (m, 3 H), 7.28 (m, 2 H), 7.07 (d, J = 7.4 Hz, 2 H), 6.74 (s, 1 H). 13C NMR (125 MHz, CDCl3): δ = 143.4, 143.3 (q, J = 39 Hz), 138.9, 131.9, 130.2, 129.2, 128.7, 128.0, 125.4, 123.4, 121.1 (q, J = 269 Hz), 105.6. LRMS: m/z calcd for C16H10BrF3N2: 367.16; found [M - 1]: 366.8. Pyrazoles could also be readily purified by column chromatography using 5-20% EtOAc-hexanes as eluent.