Wolff-Kishner reduction, Huang-Minlon

Wolff-Kishner Reduction Huang-Minlon Modification... 

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... 

The classical procedure for the Wolff-Kishner reduction—i.e. the decomposition of the hydrazone in an autoclave at 200 °C—has been replaced almost completely by the modified procedure after Huang-Minlon The isolation of the intermediate is not necessary with this variant instead the aldehyde or ketone is heated with excess hydrazine hydrate in diethyleneglycol as solvent and in the presence of alkali hydroxide for several hours under reflux. A further improvement of the reaction conditions is the use of potassium tcrt-butoxide as base and dimethyl sulfoxide (DMSO) as solvent the reaction can then proceed already at room temperature. ... 

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... 

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). 

The first report on a successful microwave-assisted one-step reduction of ketones to their respective hydrocarbons via the hydrazones appeared in 20 0 265. This so called Huang-Minlon variant of the Wolff-Kishner reduction was successfully applied to some aromatic and aliphatic aldehydes and ketones, including intermediates in the synthesis of the alkaloid flavopereirine. The reactions were performed by mixing the carbonyl compound with 2 equiv of hydrazine hydrate and an excess of powdered KOH in a commercial microwave oven. The mixtures were irradiated at 150 W for a few minutes before 250-350 W irradiations were applied (Scheme 4.39). The reaction was shown... 

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. 

Several pyridazines were prepared unintentionally by the attempted Wolff-Kishner reduction of ketoacids. It has been claimed that the ease of pyridazine formation during the Wolff-Kishner-Huang-Minlon reduction of aromatic 1,4-ketoacids depends on the nature of... 

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

Ethylene glycol (bp 197°) is a high-boiling alcohol which is useful as a solvent for reactions such as the Wolff-Kishner reduction. " For this and most other purposes it is satisfactory as purchased and may Huang-Minlon, /. Am. Chem. Soc., 68-. 2487 (1946). 

Deoxygenation of the carbonyl group of aldehydes and ketones via the intermediacy of their hydrazone derivatives, known as the Wolff-Kishner reduction,offers an alternative to the thioacetal desulfurization method. The Wolff-Kishner reduction in the presence of hydrazine and NaOH (or KOH) has been replaced largely by the Huang-Minlon method,where the deoxygenation is carried out with hydrazine in refluxing ethylene glycol. 

Many acylcyclopropanes have been converted to the corresponding alkylcyclopropanes by Wolff-Kishner reduction, in most cases under the Huang-Minlon conditions. 

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