Wolff-Kishner reaction, Huang-Minlon

This reaction is discussed extensively in an eadier review (41). In the Huang-Minlon modification of the Wolff-Kishner reaction, a high boiling solvent such as diethylene glycol is used to achieve the required high temperatures (180—210°C) without the use of pressure equipment (42). The base is generally alkaU hydroxide or an alkoxide (43). 

Huang-Minlon reduction The modification of the Wolff-Kishner reaction in which the reaction is carried out in refluxing diethylene glycol. This version has completely replaced the original method. 

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. ... 

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 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... 

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%). 

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. 

Starting from previously isolated hydrazones, it turns out that they can be reduced to the corresponding hydrocarbons by treatment with base in an aprotic solvent at temperatures significantly below the 200°C of the Huang-Minlon modification of the Wolff-Kishner reduction. However, hydrazones cannot be prepared in a one-step reaction between a ketone and hydrazine, since usually azines... 

In the synthesis of 3,4-benzpyrene from pyrene by the steps (1 -> 7), Schlude carried out the Wolff-Kishner Huang-Minlon reaction of (2a - 3) in 80% yield in lots of 100 g. by using n-butanol as solvent. Succinoylation of pyrene as previously described... 

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). 

---