Wolff-Kishner methods

Ketones can be reduced by the Wolff-Kishner method to the corresponding alkyl compounds, or by sodium in ethanol to the corresponding alcohols. An alkali-catalyzed deacylation of 3-acetyl-6-methoxypyridazine 1-oxide occurs quantitatively on treatment with dilute sodium hydroxide. 

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 desulfurization with Raney nickel of the 2,5-bis(co-carboxyoctyl)thiophene pro-... 

Modified Wolff-Kishner methods work well on ordinary cyclobutanones. Generally, the hydrazones are made at fairly mild reaction temperatures, base is added and the cyclobutane is distilled directly from the hot reaction mixture.237,272 279-284 The hydrazone can also be isolated prior to the reduction.285 The relatively facile reduction of cyclobutanones which occurs before that of larger ring ketones can be utilized in the selective reduction of cyclobutanones in the presence of, for example, a cyclohexanone, i.e. pentaspiro[3.1.3.3.3.3]heneicosane-5,11,19-trione was reduced in a stepwise manner to pentaspiro[3.1.3.3.3.3]heneicosane-5-one.237... 

Redaction of aryl carbonyl compounds.2 This reduction has been conducted traditionally by the Clemmenson or Wolff-Kishner method or by reduction of dithioketals. Actually it can be conducted in high yield with W-7 Raney nickel in 50% aqueous ethanol (2-5 hours). Nitro, halo, and cyano groups are also reduced. Examples ... 

Both chemical and catalytic methods are available to convert chromanones to chromans, and flavones to flavans. Clemmensen s method is the most commonly used and usually gives good yields, but diborane is sometimes preferable. The Wolff-Kishner method appears to degrade the pyran ring and is rarely used on chromanones. The conditions of catalytic reduction have to be rather more drastic in order to produce chromans and flavans but much depends on the activity of the catalyst and on the solvent used. If the chromanol is first formed, more severe conditions are usually required to complete the reduction (77HC(31)207>. 

Aryl alkyl ketones are readily prepared by the Friedel-Crafts acylation process (see Section 6.11.1, p. 1006) and their Clemmensen reduction constitutes a more efficient procedure for the preparation of monoalkylbenzenes than the alternative direct Friedel-Crafts alkylation reaction (see below). Alternatively aldehydes and ketones may be reduced to the corresponding hydrocarbon by the Wolff-Kishner method which involves heating the corresponding hydrazone or semicarbazone with potassium hydroxide or with sodium ethoxide solution. 

Finally, the ketone was reduced by the modified Wolff-Kishner method (cf 8) to give the final product which was free of detectable amounts of the 2,4-isomer. The 200 MHz XH NMR and mass spectrum are both in accord with the structure (cf 1). Full details of this synthesis and spectroscopic properties of the intermediates and final products will be reported elsewhere. 

Tosylhydrazones can be reduced to the corresponding alkanes under milder conditions compared to the reduction of carbonyl compounds by the Wolff-Kishner method. This is illustrated in Figure 14.60 by the reduction of the aldhydrazone A (for a possible preparation, see Table 7.2) to the alkane C. The reduction is carried out with NaBH4 in MeOH.The effective reducing agent, formed in situ, is NaBH(OMe)3. This reductant delivers a hydride ion for addition to the C=N double bond of the tosyl-hydrazone A. Thereby the hydrazide anion B is formed. Much as in the second step... 

Attempts to prepare this hydrocarbon from benzanthrone by the Wolff-Kishner method (formation and hydrolysis of the hydrazone) or its modifications, by Raney nickel reduction, or by zinc-dust distillation were either unsuccessful or gave the desired hydrocarbon in poor yield. The successful reduction using synthesis gas demonstrates further the potentialities of this new hydrogenation procedure in problems of synthetic organic chemistry. 

Reduction ofC=X to CH2 by Wolff-Kishner Methods Table 6 (continued)... 

Huang, M. Reduction of steroid ketones and other carbonyl compounds by modified Wolff-Kishner method. J. Am. Chem. Soc. 1949, 71, 3301-3303. 

These are stable compounds which do not polymerise or autoxidise. For the most part, pyrrole-aldehydes and -ketones are typical aryl-ketones, though less reactive - such ketones can be viewed as vinylogous amides. They can be reduced to alkyl-pyrroles by the Wolff-Kishner method, or by sodium borohydride via elimination from the initial alcoholic product (cf. 16.11). Treatment of acyl-l-phenylsulfonyl-pyrroles with f-butylamine-borane also effects conversion to the corresponding alkyl derivatives. ... 

The Wolff-Kishner method is particularly suitable for reduction of most carbonyl compounds.3444,507 It consists of converting the carbonyl compound into its hydrazone or, alternatively, its semicarbazone which is then decomposed by potassium hydroxide or alkoxide ... 

Some of the / -dicarbonyl compounds and substituted ketones obtained in the above-mentioned ways can be used without isolation for a wide variety of further reactions. For instance, Hiinig and his co-workers472 used such compounds for preparation of long-chain acids the 2-acylcyclohexanones obtained from A,A-dialkyl-l-cyclohexenylamine and an acyl chloride were cleaved by acid to co-acyl hexanoic acids, whose oxo groups were then reduced by the Wolff-Kishner method ... 

Desoxycholic acid (III) is commercially available, but its 7-hydroxy analog, cholic acid (I), is much more abundant in animal bile. One of the best conversions is due to Fieser and Rajagopalan (1949), who oxidized cholic acid (I) with N-bromosuccinimide to the 7-keto derivative (II), which without purification is reduced in 68% over-all yield by the Huang-Minlon modification of the Wolff-Kishner method to desoxycholic acid (III). An alternative reduction, devised by Hirschmann et al. (1951), involves the catalytic hydrogenolysis of the enol acetate of II, but the yield is inferior. 

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