Wolff-Kishner reaction mechanism

The first step in the mechanism of the Wolff-Kishner reaction consists of formation of the hydrazone (16-19). 

The first step in the mechanism " of the Wolff-Kishner reaction consists of formation of the hydrazone (16-14). It is this species that undergoes reduction in the presence of base, most likely in the following manner ... 

For item (1), the Clemmensen reduction, reduction of nitro aromatics, and the Wolff-Kishner reaction are shown. For each case, a mechanism is given showing the oxidation numbers of key atoms, a redox couple, and an overall balanced chemical equation. 

The Wharton reaction converts an epoxy ketone to an allylic alcohol by reaction with hydrazine. Propose a mechanism. (Hint Review the Wolff-Kishner reaction in Section 19.9.)... 

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. 

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... 

Similar reaction mechanisms involving a diimide intermediate (17) probably account for the conversion of the 5 a-hydroxy 6 ketone (16) into the A -steroid (18) xmder Wolff-Kishner conditions [14], and for the formation of choiest-2-ene (20) when 2a-bromocholestan-3-one (19) was treated with... 

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. 

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. 

Treatment of (736) with bromine at room temperature surprisingly yields (737) in a markedly exothermic reaction. A mechanism is discussed in which formation of a tertiary cation at C-5 followed by adamantane-protoadamantane-adamantane rearrangement is invoked for the initial stages of the reaction. In a projected synthesis of (738) it was found that Wolff-Kishner reduction of (739) gave only pyrazolone (a common reaction in such reduction of P-keto esters) and more vigorous conditions (NaOMe-MeOH-NHjNHj, sealed autoclave at 220 C) gave 1,3-adamantanedicar-boxylic acid as well as the desired material (738). The mechanism for the conversion of (739) into (738) is not clear, but reaction is dependent on both methoxide and... 

CHAmNGti Three reactions that include compound M (see Problem 62) are described here. Answer the questions that follow, (a) Treatment of M with catalytic amounts of acid in ethanol solvent causes isomerization to compound N UV = 241(17,500) and 310(72) nm. Propose a structure for N. (b) Hydrogenation of compound N (H2-Pd, ether solvent) produces compound J (Problem 62). Is this the result that you would have predicted, or is there something unusual about it (c) Wolff-Kishner reduction of compound N (H2NNH2, H2O, HO, A) leads to 3-cholestene. Propose a mechanism for this transformation. 

Kedrowski and Dougherty developed a one-pot, four-step room temperature protocol for the synthesis of allylphosphonates (6) from acyl chlorides/carboxylic acids (5) via a Wolff-Kishner-type reductive deoxygenation (Scheme 3). This method offers a low-temperature alternative to the Arbuzov reaction that works well for a variety of aliphatic acids and shows a functional group tolerance similar to that of other hydrazone-forming reactions. The investigators also proposed a mechanism for this transformation (Scheme 4). 

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