Wolff-Kishner reduction mechanism

Figure 19.11 MECHANISM Mechanism of the Wolff-Kishner reduction of an aldehyde or ketone to yield an alkane.

Not much is known about the mechanism of the Clemmensen reduction. Several mechanisms have been proposed, " including one going through a zinc-carbene intermediate. " One thing reasonably certain is that the corresponding alcohol is not an intermediate, since alcohols prepared in other ways fail to give the reaction. Note that the alcohol is not an intermediate in the Wolff-Kishner reduction either. 

Wolff-Kishner reduction of ketones bearing other functional groups sometimes gives products other than the expected methylene reduction product. Several examples are given below. Indicate a mechanism for each reaction. 

Hydrazones are important intermediates in a Wolff-Kishner reduction, a procedure for reducing a carbonyl group. An example of a Wolff-Kishner reduction appears in Figure 10-27, and the mechanism is in Figure 10-28. 

The mechanism of Wolff-Kishner reductions is exemplified in Figure 17.67 with the second step A — E of the Haworth naphthalene synthesis (steps 1 and 3 of this synthesis Fig-... 

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. 

Another reaction that can be used to accomplish the same transformation is the Wolff-Kishner reduction. In this procedure the aldehyde or ketone is heated with hydrazine and potassium hydroxide in a high boiling solvent. An example is provided in the following equation. (The mechanism for the Wolff-Kishner reduction is presented in Section 18.8.) The Clemmensen reduction and the Wolff-Kishner reduction are... 

Mechanism 18-7 Wolff-Kishner Reduction 864 Summary Reactions of Ketones and Aldehydes 865 Essential Terms 868 Study Problems 870... 

Wolff-Kishner Reduction Formation of the Hydrazone See Key Mechanism 18-5. 

Propose a mechanism for both parts of the Wolff-Kishner reduction of cyclohexanone the formation of the hydrazone, then the base-catalyzed reduction with evolution of nitrogen gas. 

Szmant, H. H. Mechanism of the Wolff-Kishner reduction, elimination, and isomerization reactions. Angew. Chem., Int. Ed. Engl. 1968, 7, 120-128. 

This reaction is usually called the Wolff-Kishner reduction.14 In early procedures, sodium ethoxide was the base commonly employed and the reaction was carried out at about 180° in a sealed tube. A simplified technique, however, has been developed for carrying out the reaction in diethylene glycol solution with sodium o potassium hydroxide Little i lmown concerning the mechanism of the reaction, but two possibilities 14(16 are shown on p. 275. 

Wolff-Kishner reduction [1,435, after citation of ref. 7], A later review discusses the mechanism of Wolff-Kishner reduction. 

The mechanism of the Wharton reaction is analogous to that of the Wolff-Kishner reduction. Addition of hydrazine to a, 3-epoxy ketone 1 gives rise to hydroxyl-hydrazine 6, which dehydrates to afford the intermediate, hydrazone 7. Tautomerization of hydrazone 7 then leads to diazene 8, a common intermediate as the Wolff-Kishner reduction. But different... 

Aldehydes and ketones react with primary amines to form imines and with secondary amines to form enamines. The mechanisms are the same, except for the site from which a proton is lost in the last step of the reaction. Imine and enamine formation are reversible imines and enamines are hydrolyzed under acidic conditions back to the carbonyl compound and amine. A pH-rate profile is a plot of the observed rate constant as a function of the pH of the reaction mixture. Hydroxide ion and heat differentiate the Wolff-Kishner reduction from ordinary hydrazone formation. 

The other methods we have studied are the Clemmensen reduction (Section 15.9A) and the Wolff-Kishner reduction (Section 15.9B). In Section 16.8C we will discuss the mechanism of the Wolff-Kishner reduction. 

Another important use of hydrazones is the Wolff—Kishner reduction, first mentioned in Section 15.9B, and whose mechanism we shall present below now that we have discussed hydrazones. 

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