Phosphonyl pyrazoles

Keywords Aldehydes, active methylene compounds, Bestmann-Ohira reagent [dimethyl(dia-zomethyl)phosphonate], potassium hydroxide, methanol, room temperamre, Knoevenagel condensation, one-pot multicomponent reaction, click chemistry, cycloaddition, phospho-nates, regioselective synthesis, phosphonyl pyrazoles... 

To a stirred solution of aldehyde (1 1 mmol), active methylene cyano derivative (2 1.2 mmol) and Bestmann-Ohira reagent (3 1.5 mmol) in distilled methanol (4 mL), was added molecular sieves followed by powdered KOH (2 mmol) and the reaction mixture was stirred at room temperature for one hour. Upon completion of the reaction (TLC monitoring), methanol was distilled off under reduced pressure. The crude residue was dissolved in ethyl acetate (50 mL) and washed with saturated ammonium chloride (2 x 20 mL). Finally the organic layer was washed with saturated brine (20 mL) and dried over anhydrous sodium sulphate. After removal of the solvent, column chromatographic purification was carried out using 0-30% acetone-dichloromethane as eluent to afford phosphonyl pyrazole 4. All the products were characterized based on spectral studies. 

Mohanan, K., Martin, A. R., Toupet, L., Smietana, M., and Vasseur, J.-J. (2010). Three-component reaction using the Bestmann-Ohiia reagrait A regioselective synthesis of phosphonyl pyrazole rings. Angew. Chem. Int. Ed., 49, 3196 3199. 

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