Wolff-Kishner reduction, Huang-Minlon modification

Wolff-Kishner Reduction Huang-Minlon Modification... 

The deoxygenation of aldehydes and ketones to the corresponding hydrocarbons via the hydrazones is known as the Wolff-Kishner reduction.28 Various modifications of the original protocols have been suggested. One of the most useful is the Huang-Minlon modification, which substituted hydrazine hydrate as a safer and less expensive replacement of anhydrous hydrazine. In addition, diethylene glycol together with sodium hydroxide was used to increase the reaction... 

The Huang-Minlon modification of the Wolff-Kishner reduction has been used innumerable times for the reduction of thiophenealde-hydes and thienyl Besides the few... 

Wohl Ziegler reaction, 926, 927 Wolff-Kishner reduction, 510, 511J, 516 Huang-Minlon modification of, 510, 516... 

The reduction of xanthone to xanthene has been achieved by using the Huang-Minlon modification of the Wolff-Kishner reduction (52JCS3741) by LAH (55JA5121) and by diphenyl-silane (61JOC4817). 

A further extension of the Huang-Minlon modification of the Wolff—Kishner reduction using similar conditions has also been reported66. 

Chattopadhyay, S., Banerjee, S.K. and Mitra, A.K., The Huang-Minlon modification of Wolff-Kishner reduction in rapid and simple way using microwave technology, /. Indian Chem. Soc., 2002, 79,906-907. 

When the Clemmensen method fails, or when strongly acidic conditions are precluded owing to the presence of acid-sensitive functional groups, the Wolff-Kishner reduction or the Huang-Minlon modification of it may succeed. The latter method is also discussed in Section 6.1.1, p. 827, and illustrated in Expt 6.4, Method A. 

Method A. Huang-Minlon modification of the Wolff-Kishner reduction. Place 36.0 g (0.3 mol) of redistilled acetophenone, b.p. 201 °C, 300 ml of diethylene glycol, 30ml of 90 per cent hydrazine hydrate (CAUTION) and 40g of potassium hydroxide pellets in a 500-ml two-necked round-bottomed flask fitted with a reflux condenser insert a thermometer supported in a screw-capped adapter in the side-neck so that the bulb dips into the reaction mixture. Warm the mixture on a boiling water bath until most of the potassium hydroxide has dissolved and then heat under reflux for 1 hour either by means of a free flame or by using a heating mantle. Remove the reflux condenser and fit a still-head and condenser for downward distillation. Distil until the temperature of the liquid rises to 175 °C (1). Separate the upper hydrocarbon layer from the distillate and extract the aqueous layer twice with 20 ml portions of ether. Dry the combined upper layer and ethereal extracts with magnesium sulphate, remove the ether on a water bath and distil the residue. Collect ethylbenzene at 135-136 °C the yield is 20 g (62.5%). 

The Wolff-Kishner reduction is an old and still often used method for the reduction of a ketone to the corresponding alkane. The Huang-Minlon modification of this reduction is commonly employed. It entails the treatment of the ketone with hydrazine hydrate and KOH in diethylene glycol, first at low temperature and then at reflux (200 °C). 

Starting from isolated hydrazones, reduction to the corresponding hydrocarbons by treatment with base in an aprotic solvent takes place at temperatures significantly below the 200 °C of the Huang-Minlon modification of the Wolff-Kishner reduction. However, hydra-zones cannot be prepared in a one-step reaction between a ketone and hydrazine, since usually azines (R1R2C=N=N=CR1R2) are formed instead. However, semicarbazones are hydrazone derivatives that are easily accessible by the reaction of a ketone with semicarbazide (for the mechanism, see Table 9.2). Semicarbazones can be converted into alkanes with KO/Bu in toluene at temperatures as low as 100 °C. This method provides an alternative to the Wolff-Kishner reduction when much lower than usual reduction temperatures are desirable. 

Table 1 Wolff-Kishner Reduction of Carbonyls Using the Huang-Minlon Modification...

Desoxycholic acid (III) is commercially available, but its 7-hydroxy analog, cholic acid (I), is much more abundant in animal bile. One of the best conversions is due to Fieser and Rajagopalan (1949), who oxidized cholic acid (I) with N-bromosuccinimide to the 7-keto derivative (II), which without purification is reduced in 68% over-all yield by the Huang-Minlon modification of the Wolff-Kishner method to desoxycholic acid (III). An alternative reduction, devised by Hirschmann et al. (1951), involves the catalytic hydrogenolysis of the enol acetate of II, but the yield is inferior. 

A method of almost universal applicability for the deoxygenation of carbonyl compounds is the Wolff-Kishner reduction While the earlier reductions were carried out in two steps on the derived hydrazone or semicarbazone derivatives, the Huang-Minlon modification is a single-pot operation. In this procedure, the carbonyl compound and hydrazine (hydrate or anhydrous) are heated (180-220 °C) in the presence of a base and a proton source. Sodium or potassium hydroxide, potassium-t-butoxide and other alkoxides are the frequently used bases and ethylene glycol or its oligomers are used as the solvent and proton source. Over the years, several modifications of this procedure have been used to cater to the specific needs of a given substrate. The Wolff-Kishner reaction works well with both aldehydes and ketones and remains the most routinely used procedure for the preparation of alkanes from carbonyl compounds (Table 9). This method is equally suitable for the synthesis of polycyclic and hindered alkanes. 

WolfT-Kishner Reduction. A particularly useful reaction of the (V-silyl hydrazones is their use as substrates in the Wolff-Kishner reaction, where reduction of the corresponding carbonyl compound can be accomplished at relatively modest temperatures. This is in marked contrast to the more traditional Wolff-Kishner reaction, and its Huang-Minlon modification, which require high temperatures and the use of potassium hydroxide. ... 

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