Reduction reactions Wolff-Kishner

Williamson synthesis Wohl-Ziegler reaction Wolff rearrangement Wolff Kishner reduction Wurtz reaction Wurtz-Fittig reaction... 

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)... 

Several methods are available to supplement the phenol alkylations described above. Primary alkylphenols can be produced using the more traditional Friedel-Crafts reaction. Thus an -butylphenol can be synthesized direcdy from a butyl haUde, phenol, and mild Lewis acid catalyst. Alternatively, butyryl chloride can be used to acylate phenol producing a butyrophenone. Reduction with hydrazine (a Wolff-Kishner reduction) generates butylphenol. 

Beckmann rearrangement, 4, 292 pyrolysis, 4, 202 synthesis, 4, 223 Wittig reaction, 4, 294 Wolff-Kishner reduction, 4, 291 Indole, 1-acyl-2,3-disubstituted photoisomerization, 4, 204 photo-Fries rearrangement, 4, 204 photoisomerization, 4, 42 synthesis, 4, 82 Indole, 2-acyl acidity, 4, 297 synthesis, 4, 337, 360 Indole, 3-acyl-acidity, 4, 297 cleavage, 4, 289 reduction, 4, 289 synthesis, 4, 360 Indole, 7-acyl-synthesis, 4, 246... 

Both the Wolff-Kishner and Clemmensen reductions of a, -unsaturated ketones give olefins. There has been considerable confusion concerning the exact product composition in the case of A -3-ketones. Wolff-Kishner reduction gives A" -, 5a-A - and 5 -A -olefins, and, depending on the substrate reaction conditions and work-up, any one or more of these may be isolated. (See ref. 287 for a recent review of the Wolff-Kishner reduction.)... 

The stereochemistry of the product resulting from the reaction of a 17-keto steroid with ethylidenetriphenylphosphorane is different from that of the 17-ethylidene steroids obtained by dehydration of 17a-ethyl-17/ -hydroxy compounds, Wolff-Kishner reduction of A -20-keto steroids or by sodium-alcohol or sodium-ammonia " reductions of 17-ethynyl carbinols. These latter products have generally been assumed to possess the trans configuration (C-21 methyl away from the bulk of the ring system) because of anticipated greater stability. The cis configuration for... 

The latter compound can be isolated from the reaction mixture by chromatography on acid-washed alumina. Similar treatment of the trans-ketone (117a) followed by isolation and chromatography on alumina gives the same equilibrium mixture. The structure of the thermodynamically more stable ketone (116a) was proved by its conversion by Wolff-Kishner reduction to the hydrocarbon (118) independently synthesized from the known... 

An interesting bridged-sulfur compound, which is a natural constituent of Iranian oil, has been synthesized 478) by the reaction of a bicyclic bis-enamine with sulfur dichloride and subsequent Wolff-Kishner reduction of an initial sulfur-bridged diketone. Sulfur dichloride has also been added to a number of vinylogous amides 479). 

The tritylone ether is used to protect primary hydroxyl groups in the presence of secondary hydroxyl groups. It is prepared by the reaction of an alcohol with 9-phenyl-9-hydroxyanthrone under acid catalysis (cat. TsOH, benzene, reflux, 55-95% yield). It can be cleaved under the harsh conditions of the Wolff-Kishner reduction (H2NNH2, NaOH, 200°, 88% yield) and by electrolytic reduction (—1.4 V, LiBr, MeOH, 80-85% yield)". It is stable to 10% HCl, 55 h. ... 

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. 

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 Wolff-Kishner reduction is an important alternative method to the Clem-mensen reduction, and is especially useful for the reduction of acid-labile or high-molecular substrates. Yields are often below 70%, due to various side-reactions such as elimination or isomerization reactions. ... 

Docosanedioic acid has been prepared by Wolff-Kishner reduction of 6,17-diketodocosanedioic acid, formed by reaction of the half-ester acid chloride of adipic acid with the a,co-cadmium derivative of decane (%26 overall yield).3 Reduction of Wolff-Kishner method, followed by simultaneous reduction and desulfurization with Raney nickel of the 2,5-bis(co-carboxyoctyl)thiophene pro-... 

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. 

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... 

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. 

The hydrazone was subsequently treated with KOH under the action of MW to undergo Wolff-Kishner reduction (leading to PhCH2Ph) within 25-30 min in excellent yields (95 %). As an extension, the reaction of neat 5- or 8-oxobenzopyran-2(lH)-ones with a variety of aromatic and heteroaromatic hydrazines is substantially accelerated by irradiation in the absence of any catalyst, solid support, or solvent [66] (Eq. 14). 

This reaction sequence illustrates how the rates of many base-catalyzed reactions can be enhanced greatly by substitution of dimethylsulfoxide for the usual hydroxylic solvents. Other examples of the enhanced reactivity of anions in dimethylsulfoxide are found in Wolff-Kishner reductions and Cope elimination reactions. The present reaction illustrates the generation of an aryne intermediate from bromobenzene. ... 

Friedel-Crafts acylation of dibenzothiophene with succinic anhydride is known to occur in the 2-position, yielding y-oxo-2-dibenzothiophene-but3Tic acid (135a). Subsequent Wolff-Kishner reduction and internal cyclization yields 7-keto-7,8,9,10-tetrahydrobenzo[6]naphtho[2,3-d]thio-phene (136a). - This reaction has been extended to 4-methyldibenzo-... 

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