Aldehydes, Wolff-Kishner

The normal reactivity of carbonyl derivatives (e.g., hydrazone formation of aldehydes, Wolff-Kishner reduction of ketones to alkylpyridazines, sodium in ethanol reduction of ketones to alcohols) was very briefly discussed in CHEC-I <84CHEC-i(3B)l>. Some examples of reactions are given here. 

Wolff - Kishner reduction of aldehydes and ketones. Upon heating the hydrazoiie or semicarbazone of an aldehyde or ketone with potassium hydroxide or with sodium ethoxide solution (sealed tube), the corresponding hydrocarbon is obtained ... 

Both the Clemmensen and the Wolff-Kishner reductions are designed to carry out a specific functional group transformation the reduction of an aldehyde or ketone carbonyl to a methylene group Neither one will reduce the carbonyl group of a carboxylic acid nor... 

Table 17 2 summarizes the reactions of aldehydes and ketones that you ve seen m ear her chapters All are valuable tools to the synthetic chemist Carbonyl groups provide access to hydrocarbons by Clemmensen or Wolff-Kishner reduction (Section 12 8) to alcohols by reduction (Section 15 2) or by reaction with Grignard or organolithmm reagents (Sections 14 6 and 14 7)... 

Wolff-Kishner reduction (Section 12 8) Method for reducing the carbonyl group of aldehydes and ketones to a methylene... 

Common catalyst compositions contain oxides or ionic forms of platinum, nickel, copper, cobalt, or palladium which are often present as mixtures of more than one metal. Metal hydrides, such as lithium aluminum hydride [16853-85-3] or sodium borohydride [16940-66-2] can also be used to reduce aldehydes. Depending on additional functionahties that may be present in the aldehyde molecule, specialized reducing reagents such as trimethoxyalurninum hydride or alkylboranes (less reactive and more selective) may be used. Other less industrially significant reduction procedures such as the Clemmensen reduction or the modified Wolff-Kishner reduction exist as well. 

Carbonyl deductions. The classical Wolff-Kishner reduction of ketones (qv) and aldehydes (qv) involves the intermediate formation of a hydrazone, which is then decomposed at high temperatures under basic conditions to give the methylene group, although sometimes alcohols may form (40). 

Another important synthetic method for the reduction of ketones and aldehydes to the corresponding methylene compounds is the Woljf-Kishner reduction. This reaction is carried out under basic conditions, and therefore can be applied for the reduction of acid-sensitive substrates it can thus be regarded as a complementary method. The experimental procedure for the Clemmensen reduction is simpler however for starting materials of high molecular weight the Wolff-Kishner reduction is more successful. 

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 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. ... 

A useful variant of the imine-forming reaction just discussed involves the treatment of an aldehyde or ketone with hydrazine, H2NNH2, in the presence of KOH. Called the Wolff-Kishner reaction, the process is a useful and genera method for converting an aldehyde or ketone into an alkane, r2c=o —> R2CH2. 

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

Wolff-Kishner reaction (Section 19.9) The conversion of an aldehyde or ketone into an alkane by reaction with hydrazine and base. 

Reduction of aldehydes or ketones (Wolff-Kishner Clemmensen)... 

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... 

Hydrogenolysis of an aldehyde or ketone carbonyl to >CH2 is an important organic transformation, and classical procedures such as the Clemmenson and Wolff-Kishner reactions have limitations (24, 25) heterogeneous catalytic systems and several two-step procedures are also known (1, 24, 26). Our observation of this conversion in what is essentially a 2-phase medium... 

This silyl hydrazone formation-oxidation sequence was originally developed as a practical alternative to the synthesis and oxidation of unsubstituted hydrazones by Myers and Furrow [31]. The formation of hydrazones directly from hydrazine and ketones is invariably complicated by azine formation. In contrast, silyl hydrazones can be formed cleanly from /V,/V -bis(7< rt-butyldimethylsilyl)hydrazine and aldehydes and ketones with nearly complete exclusion of azine formation. The resulting silylhydrazones undergo many of the reactions of conventional hydrazones (Wolff-Kishner reduction, oxidation to diazo intermediate, formation of geminal and vinyl iodides) with equal or greater efficiency. It is also noteworthy that application of hydrazine in this setting may also have led to cleavage of the acetate substituents. 

An important reduction reaction is Wolff-Kishner reduction of carbonyl group on aldehydes and ketones to form hydrazone ... 

Ganter has developed three different approaches to tricyclo[5.2.1.0 ]decane (403), yet another of the nineteen isomeric hydrocarbons of adamantaneland As seen in Scheme XXXIII, the routes involve intramolecular cyclization of keto tosylate 399 followed by Wolff-Kishner reduction of the resulting ketone, thermo-cyclization of 400 and subsequent dechlorination, hydrogenation, and photocycli-zation of aldehydes 401. Majerski s approach involved hypoiodite cleavage of alcohol 402... 

In the latest development of his elegant work with hydrazone derivatives, Andrew Myers of Harvard reports (J. Am. Chem. Soc. 2004,126, 5436) that Sc(OTf), catalyzes the addition of l,2-bis(r-butyldimethylsilyl)hydrazine, to aldehydes and ketones to form the t-butyldimethylsilylhydrazones. Addition of tBuOH/tBuOK in DMSO to the crude hydrazone effects low temperature Wolff-Kishner reduction. Alternatively, halogenation of ketone hydrazones can lead to vinyl halides such as 11, or the 1,1-dihalo derivatives, depending on conditions. Halogenation of aldehyde hydrazones provides the 1,1-dihalo derivatives such as 13. 

The carbonyl reactivity of pyrrole-, furan-, thiophene- and selenophene-2- and -3-carbaldehydes is very similar to that of benzaldehyde. A quantitative study of the reaction of Af-methylpyrrole-2-carbaldehyde, furan-2-carbaldehyde and thiophene-2-carbaldehyde with hydroxide ions showed that the difference in reactivity between furan- and thiophene-2-carbaldehydes was small but that both of these aldehydes were considerably more reactive to hydroxide addition at the carbonyl carbon than A-methylpyrrole-2-carbaldehyde (76JOC1952). Pyrrole-2-aldehydes fail to undergo Cannizzaro and benzoin reactions, which is attributed to mesomerism involving the ring nitrogen (see 366). They yield 2-hydroxymethylpyrroles (by NaBH4 reduction) and 2-methylpyrroles (Wolff-Kishner reduction). The IR spectrum of the hydrochloride of 2-formylpyrrole indicates that protonation occurs mainly at the carbonyl oxygen atom and only to a limited extent at C-5. 

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