Clemmensen reduction carbonyl compounds

The disadvantages associated with the Clemmensen reduction of carbonyl compounds (see 3 above), viz., (a) the production of small amounts of carbinols and unsaturated compounds as by-products, (h) the poor results obtained with many compounds of high molecular weight, (c) the non-appUcability to furan and pyrrole compounds (owing to their sensitivity to acids), and (d) the sensitivity to steric hindrance, are absent in the modified Wolff-Kishner reduction. 

Clemmensen reaction is the reduction of carbonyl compounds with amalgamated zinc and concentrated hydrochloric acid... 

Deuteration of a Diterpene Carbonyl Compound by Clemmensen Reduction... 

Deuteration of a diterpene carbonyl compound by Clemmensen reduction, 170... 

More direct methods may be used, depending on the character of the R groups of the carbonyl compound. If the R groups are stable to a variety of reagents there is no problem, but with sensitive R groups not all methods are equally applicable. When the R groups are stable to acid but unstable to base, the Clemmensen reduction with amalgamated zinc and hydrochloric acid is often very useful. 

When the carbonyl compound is sensitive to both acids and bases, or for other reasons gives poor yields in both the Clemmensen and Wolff-Kishner reductions, a recourse may be reduction of the corresponding thioacetal or thioketal with hydrogen-saturated Raney nickel (Section 11-2B) ... 

The Clemmensen reduction was accompanied by D/H exchange via acid-catalysed enolization of the carbonyl group, resulting in the production of deuteriated compounds 57 and 58 with various numbers of deuterium atoms. The mixture of the compound 59 obtained by the Wolf-Kishner reduction was predominantly labelled at position 2. This has been proved by the 13C-NMR spectrum. Isotope shift and loss intensivity on substituted C(2) carbon signals have been observed54,55. 

Some features of the Clemmensen reduction are discussed in Section 5.1.3, p. 476. Purely aromatic ketones generally do not give satisfactory results pinacols and resinous products often predominate. The reduction of ketonic compounds of high molecular weight and very slight solubility is facilitated by the addition of a solvent, such as ethanol, acetic acid or dioxane, which is miscible with aqueous hydrochloric acid. With some carbonyl compounds, notably keto acids, poor yields are obtained even in the presence of ethanol, etc., and the difficulty has been ascribed to the formation of insoluble polymolecular reduction products, which coat the surface of the zinc. The addition of a hydrocarbon solvent, such as toluene, is beneficial because it keeps most of the material out of contact with the zinc and the reduction occurs in the aqueous layer at such a high dilution that polymolecular reactions are largely inhibited (see Expt 6.123). 

Clemmensen Reduction (Review) The Clemmensen reduction commonly converts acylbenzenes (from Friedel-Crafts acylation, Section 17-1 IB) to alkylbenzenes, but it also works with other ketones and aldehydes that are not sensitive to acid. The carbonyl compound is heated with an excess of amalgamated zinc (zinc treated with mercury) and hydrochloric acid. The actual reduction occurs by a complex mechanism on the surface of the zinc. 

The third method is the simplest to do, but has the most complicated mechanism. The Clemmensen reduction is also rather violent, and really reasonable only for compounds with just the one functional group. It uses zinc metal dissolvmg in hydrochloric acid. As the metal dissolves, it gives up two electrons—in the absence of something else to do, these electrons would reduce the H+ in the acid to H2, and give ZnCl2 and H2. But in the presence of a carbonyl compound, the electrons go to reduce the C=0 bond. 

Clemmensen reduction, of carbonyl compounds, 5 of keto acids, 432 Conrad-Limpack-Knorr synthesis of quinolines, 847... 

The reduction of carbonyl compounds to hydrocarbons may be achieved under acidic conditions e.g. the Clemmensen reduction with zinc and concentrated hydrochloric acid), basic conditions (e.g. the Wolff-Kishner reduction of a hydrazone with alkali) or neutral conditions (e.g. the catalytic reduction of thioketals with Raney nickel). The carbonyl group may represent the residue from an earlier step in the synthesis of a compound. 

Because of carbonium ion generation, aromatic aldehydes and ketones can usually be reduced more easily than the corresponding aliphatic compounds. However, a modified Clemmensen reduction is an effective method to reduce isolated aliphatic carbonyl groups directly to methylene groups, and typical examples are shown in equations (4)-(6)." ... 

Electrolysis of carbonyl compounds provides pinacols, alcohols or hydrocarbons, depending on the conditions, such as pH, the nature of the electrode, and its potential. Fundamental studies have been carried out on the mechanisms of hydrocarbon formation using acetone as a substrate. Although several electrodes, such as Cd, Pt, Pb or Zn, are recommended, carbonyl compounds, including aryl and alkyl derivatives, require strong aqueous acidic media for reduction to the hydrocarbons. The mechanism of the electrolytic reduction is probably similar to that of Clemmensen reduction, which starts from anion radical formation by one-electron transfer, as indicated in Scheme 3. The difference is that electrolytic reduction takes place in an electric double layer, rather than on the surface of the zinc metal. 

This type of compound is called a hydrazone, and is the first intermediate in a very important reaction called the Wolff-Kishner reduction. This reaction, along with the Clemmensen reduction (which we will discuss in more detail in the chapter on redox reactions), is one of the principal methods for reducing a carbonyl compound to the corresponding alkane, i.e. R2C=0 to R2CH2. In... 

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. 

Similar to the Wolff-Kishner Reduction and Clemmensen Reduction, this reaction is also useful for the conversion of carbonyl compounds into hydrocarbons and olefins. 

Clemmensen, E. Ber. 1913, 46, 1837-1843. Erik C. Clemmensen (1876-1941) was bom in Odense, Denmark. He received the M.S. degree from the Royal Polytechnic Institute in Copenhagen. In 1900, Clemmensen immigrated to the United States, and worked at Parke, Davis and Company in Detroit as a research chemist for 14 years, where he discovered the reduction of carbonyl compounds with amalgamated zinc. Clemmensen later founded a few chemical companies and was the president of one of them, the Clemmensen Chemical Corporation in Newark, New Jersey. 

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