Example of the Wolff-Kishner Reduction Procedure Suitable for an Undergraduate Organic Lab Experiment Preparation of Oxindole David S. Sorlano University of Pittsburgh at Bradford, Bradford, PA 16701
Carbonyl groups are reduced to methylenes by treatment with hydrazine hydrate in the presence of a strong base, usually at elevated temperatures (-200 '0. The WOW-Kishner reaction is carried in most current organic introductory textbooks where it is described along with the Clemmensen reduction ( I ) . The following transformation (isatin to oxindole hvdrazone to oxindole) is a suitable demonstration of the title reaction that is canied out under notably mild conditions, in a typical 3-4 h laboratory period (2).
Reaction Sequence Preparation of IsatinJ-Hydrazone (2)
Isatin 1(Aldrich Chemical, 25.0 g, 147 g-mol, 0.17 mol ) is suspended in 200 mL of anhydrous methanol and 30.0 g of hydrazine hydrate (Aldrich, 55% hydrazine content, 0.425 mol) is added in one or ti on. The solution is heated
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Journal of Chemical Education
Wolff-Kishner Reduction: Preparation of Oxindole (2-I~d~linone)
~ a watch glass to air m i l e the above crystals are l e on dry, 2,0 g, of metal is dissolved in 50.0 mL of ahsolute ethanol in a round-bottomed flask
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* Caution:Hvdroeen eas evolution ! . When the sodium has completely dissolved, 5,0 of the above hydrazone derivative is added in small portions, with shaking, at 60-70 'C, over a 10-miu interval. The solution is heated to reflux until the evolution of nitrogen gas has ceased (-30 m i d . The brown solution is then carefully poured on ice and acidified to pH = 1with 10% HC1 solution. The mixture is extracted with 2 x 25 mL of ether, dried over calcium chloride, filtered, and concentrated to yield a crude, light-orange residue. The mass is recrystallized from 50 mL of water (a small amount ofcharcoal is added) to yield 3.0 g of oxindole (73 % yield) as white needles (m,p,: 125-127 +C), Literature Cited
