Wolff-Kishner deoxygenation

We have already seen that the products of Friedel-Crafts acylations may be converted into alkyl benzenes by using Cletnmensen reduction. Wolff-Kishner deoxygenation also is frequently employed for this purpose and is particularly useful for add-sensitive, base-stable substrates. 

An aldehyde or ketone 1 can react with hydrazine to give a hydrazone 2. The latter can be converted to a hydrocarbon—the methylene derivative 3—by loss of Na upon heating in the presence of base. This deoxygenation method is called the Wolff-Kishner reduction. ... 

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... 

In actual use, H2 is not a good reagent for deoxygenation of ketones and aldehydes. Deoxygenation can be accomplished by either the Clemmensen reduction (under acidic conditions) or the Wolff-Kishner reduction (under basic conditions). 

A four-electron reduction that replaces the carbonyl oxygen atom of a ketone or aldehyde with two hydrogen atoms. The Clemmensen reduction and the Wolff-Kishner reduction are the two most common methods of deoxygenation, (p. 863)... 

Since its introduction early in this century, the deoxygenation of aldehydes and ketones to methyl or methylene derivatives, respectively, via base treatment of hydrazone intermediates (equation 1) has proven to be one of the most convenient and synthetically useful processes available for this important type of transformation. The reaction is termed the Wolff-Kishner reduction in recognition of the two original independent discoverers.However, the initial recipes introduced proved tedious and unreliable with many structural, especially hindered, examples. This led to substantial efforts devoted over the years to developing more convenient and successful experimental procedures, resulting in a number of improved and more reliable modifications which are most often utilized at present. More recently, modified procedures have been provided which utilize hydride reductions of p-toluenesulfonylhydrazone (to-sylhydrazone) derivatives and subsequent decomposition to release the hydrocarbon products under much milder and less basic conditions than those normally required for Wolff-Kishner reductions (equation 2). 

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. 

The asymmetric syntheses of (-)-methyl kaur-16-en-19-oate and (-)-methyl trachyloban-19-oate was achieved by M. lhara and co-workers. One of the last transformations was the deoxygenation of the ketone carbonyl group of the tetracyclic intermediate, which was effected by the Wolff-Kishner reduction. Under the strongly basic conditions the ester functionality was hydrolyzed, so an esterification using diazomethane was necessary as the final step. The major deoxygenated product was (-)-methyl kaur-16-en-19-oate (59%). The minor product was identified as (-)-methyl trachyloban-19-oate (16%). 

Wolff-Kishner reduction Deoxygenation of aldehydes and ketones under basic conditions to give hydrocarbons via the corresponding hydrazones or semicarbazones. 496... 

This method of directly reducing ephedrine, pseudoephedrine, or phenylpropanolamine to meth or benzedrine uses hydrazine hydrate as the reducing agent. The Wolff-Kishner reduction is generally used to deoxygenate ketones to the corresponding hydrocarbon, but in this case, it can be used on these particular substances to reduce them. No doubt, this is because the benzyl alcohol grouping has a ketone nature due to tautomerism. 

In Section 15.15, we saw that when a ketone or an aldehyde is heated in a basic solution of hydrazine, the carbonyl group is converted into a methylene group. This process is called deoxygenation because an oxygen is removed from the reactant. The reaction is known as the Wolff-Kishner reduction. 

Hydroxide ion and heat differentiate the Wolff-Kishner reduction from ordinary hydrazone formation. Initially, the ketone reacts with hydrazine to form a hydrazone. After the hydrazone is formed, hydroxide ion removes a proton from the NH2 group. Heat is required because this proton is not easily removed. The negative charge can be delocalized onto carbon, which abstracts a proton from water. The last two steps are repeated to form the deoxygenated product and nitrogen gas. 

Deoxygenation of aryl ketones. The convenient reduction is particularly distinguished by its mildness, in comparison with Clemmensen and Wolff-Kishner reductions. 

The reduction of C=0 to CH2 may be achieved in three ways Raney nickel desulfurization of thioketals (Section 17-8), Clemmensen reduction (Section. 16-5), and, as described here, WolfF-Kishner reduction. Because there are many ways to make carbonyl compounds, and carbonyl compounds are great places to start for making new carbon-carbon bonds, you will find that carbonyi groups are often present when complex molecules are made from simpler ones. This will be especially evident in Chapters 18-20 and 23. Deoxygenation will be useful if you need to get rid of a carbonyl group that has been used to construct bonds in a large molecule but is not wanted in the final product. The example of Friedel-Crafts alkanoylation followed by deoxygenation is just the first that you will see. 

Wolff-Kishner reduction The decomposition of hydrazones in the presence of a base, used to deoxygenate aldehydes and ketones. 

The reductive deoxygenation of acyl substituents is one of the classic methods for introduction of primary alkyl groups on aromatic rings. For benzene derivatives, the Wolff-Kishner and Clem-... 

Wolff-Kishner reduction Deoxygenation of a ketone or aldehyde by conversion to the hydra-zone, followed by treatment with a strong base. (p. 854)... 

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. 

Synthetic strategy Multi-component one-pot protocol for the Wolff-Kishner type reductive deoxygenation of acyl phosphonates... 

Keywords Carboxylic acids, acyl chlorides, dichloromethane, room temperature, Arbuzov reaction, acyl phosphonates, Wolff-Kishner type reductive deoxygenation, alkyl phosphonates... 

In Section 17-5 we reviewed methods by which carbonyl compounds can be reduced to alcohols. Reduction of the C=0 group to CH2 (deoxygenation) also is possible. Two ways in which this may be achieved are Clemmensen reduction (Section 16-5) and thioacetal formation followed by desulfurization (Section 17-8). This section presents a third method for deoxygenation—the Wolff-Kishner reduction. 

Wolff-Kishner reduction complements the Cletnmensen and thioacetal desulfurization methods of deoxygenating aldehydes and ketones. Thus, the Clemmensen reduction is unsuitable for compounds containing acid-sensitive groups, and hydrogenation of multiple bonds can accompany desulfurization with hydrogen and Raney nickel. Such functional groups are generally not affected by Wolff-Kishner conditions. 

In Summary The Wolff-Kishner reduction is the decomposition of a hydrazone by base, the second part of a method of deoxygenating aldehydes and ketones. It complements Clemmensen and thioacetal desulfurization procedures. 

Wolff—Kishner reduction Deoxygenation of an aldehyde or ketone converting a carbonyl group to... 

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). 

Scheme 3 Synthesis of alkylphosphonates from acyl chlorides/carboxylic acids via a Wolff-Kishner-type reductive deoxygenation.

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