Wolff-Kishner reduction, use

To 1,400 ml of an approximately 50% water/triglycol solution of the potassium salt of cheno-deoxycholic acid, obtained by the Wolff-Kishner reduction (using hydrazine hydrate and potassium hydroxide) from 50 g of 7-acetyl-12-ketochenodeoxycholic acid, 220 ml of dilute hydrochloric acid is added to bring the pH to 2. The solution is stirred and the crude cheno-deoxycholic acid precipitates. The precipitate is recovered and dried to constant weight at about 60°C. About 36 g of the crude chenodeoxycholic acid, melting in the range of 126°-129°C, is obtained. 

A further extension of the Huang-Minlon modification of the Wolff—Kishner reduction using similar conditions has also been reported66. 

The Wolff-Kishner reduction uses hydrazine and base. 

The Wolff-Kishner reduction uses hydrazine (NH2NH2) and strong base (KOH). 

Friedel-Crafts acylation followed by Clemmensen or Wolff-Kishner reduction is a standard sequence used to introduce a primary alkyl group onto an aromatic ring... 

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. 

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. 

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. ... 

The Huang-Minlon modification of the Wolff-Kishner reduction has been used innumerable times for the reduction of thiophenealde-hydes and thienyl Besides the few... 

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. ... 

Note that the Wolff-Kishner reduction accomplishes the same overall trans-fonnation as the catalytic hydrogenation of an acylbenzene to yield an alkyl-benzene (Section 16.10). The Wolff-Kishner reduction is more general and more useful than catalytic hydrogenation, however, because it works well with both alkyl and atyl ketones. 

The procedure outlined is much quicker and simpler than previous methods Starting materials are readily available, and the preparation can be run on any scale in the length of a day. Because exclusion of a basic catalyst eliminates the Wolff-Kishner reduction of the cinnamalhydrazone, separation of the 5-phenylpyrazoline from cinnamalhydrazone, or of phenylcyclopropane from propenylbenzene, does not have to be effected. The present procedure can also be used to convert other ring-substituted cinnamaldehydes to the corresponding arylcyclo-propanes... 

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... 

The usual method of carrying out of Wolff-Kishner reduction is to heat a hydrzone in presence of a base at about 200°. But by using DMSO as solvent and potassium t.butoxide as base, the reduction can be carried at room temperature. 

Bhattacharyya et al. reported the first total synthesis of clausenalene (90) to establish its structure (99). This total synthesis uses Japp-Klingemann and Fischer-Borsche reactions as key steps. The phenyl hydrazone 1000 required for the transformation to 1-0x0-tetrahydrocarbazole 1001 under Fischer-Borsche conditions was obtained by condensation of 2-hydroxymethylene-5-methylcyclohexanone (999) with diazotized 3,4-methylenedioxyaniline (998) using Japp-Klingemann conditions. Wolff-Kishner reduction of 1001 furnished 3-methyl-6,7-methylenedioxy-l,2,3,4-tetrahydrocarbazole (1002), which, on aromatization wifh 10% Pd/C in decalin, afforded clausenalene (90) (99) (Scheme 5.143). 

Stille cross-coupling and reductive N-heteroannulation steps. lodination of 1033, followed by Stille cross-coupling of the corresponding iodo derivative 1034 with the arylstannane 1035, gave the annotation precursor 1036. Reductive N-heteroannula-tion of 1036 afforded the carbazolone 1001, which was previously (99) (see Scheme 5.143) used to prepare clausenalene (90) via a Wolff-Kishner reduction followed by aromatization (659) (Scheme 5.155). 

Sometimes the acidic conditions used in the Clemmensen reduction are unsuitable for certain molecules. In these cases, Wolff-Kishner reduction is employed, which occurs in basic conditions. 

A common alternative to the Wolff-Kishner reduction of cyclobutanones to the parent cyclobutane (see Section S.2.4.2.), is formation of thiocetals (see Section 5.2.4.7.1.) followed by hydrogenolyses using Raney nickel.64,146-149 For example, l,4,4-trimethyl-6,6-(propane-l,3-diyldithia)bicyclo[3.2.0]heptan-3-one gave 15 using this method. It was found that the W-2 quality of Raney nickel works well.64"148... 

Methyl- 1,3-cyclopentanedione is a key intermediate for the total synthesis of steroids.2 A number of methods have been described for its preparation, among them the condensation of succinic acid with propionyl chloride,3 and that of succinic anhydride with 2-buten-2-ol acetate,4 both in the presence of aluminum chloride. It has also been obtained from 3-methylcyclopentane-1,2,4-trione by catalytic hydrogenation5 and Wolff-Kishner reduction 6 The base-promoted cyclization of 4-oxohexanoic acid ethyl ester and diethyl propionylsuccinate with tertiary alkoxides was first reported by Bucourt.7 The present cyclization process provides an experimentally simple route to 2-methyl-1,3-cyclopentanedione. Using the same procedure, 4-oxoheptanoic acid ethyl ester has been cyclized to give 2-ethyl-l,3-cyclopentanedione in 46% yield... 

The three-step sequence used to convert enone 65 to miltirone (56) is shown in Scheme 5.7 and consists of, first, a Wolff-Kishner reduction to convert the C(5) carbonyl moiety into a methylene, followed by deprotection of the aryl methyl ethers and oxidation to an ortho-quinone using ceric ammonium nitrate. The physical and spectroscopic data of our synthetic miltirone are identical with those reported for the natural material. 

In any event, isolation is tedious and yields of single olefin are not very good,255,273 288 although the use of potassium /-butoxide is reported to favor formation of the A4-olefin in good yield.289 It has been shown290 that Wolff-Kishner reduction of a,/ -unsaturated ketones involving double bond shift involves a nonsymmetrical intermediate. 

Alkylfurans are usually obtained by ring synthesis, decarboxylation of alkylfurancarboxy-lic acids, Wolff-Kishner reduction of aldehydes or ketones, or by reduction of halomethyl groups with zinc and acetic acid or LAH (79JOC3420) alkylation is of limited value. The chemistry of these compounds is conventional but oxidation to furancarboxylic acids cannot usually be carried out due to the lability of the ring. NBS bromination (Section 3.11.2.2.5) is a useful route to side-chain substituted compounds but reduction of esters to hydroxymethyl groups and subsequent transformation is often preferable. The haloalkyl compounds are extremely sensitive to resinification but if adequate precautions are taken they are... 

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