Zinc, amalgamated Clemmensen reduction

Zinc amalgam (for Clemmensen reduction) may be prepared by either of the following two methods. 

The Clemmensen reduction of aldehydes and ketones to methyl or methylene groups takes place by heating with zinc and hydrochloric acid. A non-miscible solvent can be used and serves to keep the concentration in the aqueous phase low, and thus prevent bimolecular condensations at the metal surface. The choice of acid is confined to the hydrogen halides, which appear to be the only strong acids whose anions are not reduced with zinc amalgam. The Clemmensen reduction employs rather vigorous conditions and is not suitable for the reduction of polyfunctional molecules, such as 1,3- or 1,4-diketones, or of sensitive compounds. However, it is effective for simple compounds that are stable to acid (7.38). A modification under milder conditions uses zinc dust and HCl dissolved in diethyl ether (ethereal HCl). Other methods for converting C=0 to CH2 are described in Schemes 7.87 and 7.105. 

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. 

Clemmensen reduction Aldehydes and ketones may generally be reduced to the corresponding hydrocarbons by healing with amalgamated zinc and hydrochloric acid. 

Aliphatic hydrocarbons can be prepared by the reduction of the readily accessible ketones with amalgamated zinc and concentrated hydrochloric acid (Clemmensen method of reduction). This procedure is particularly valuable for the prep>aration of hydrocarbons wdth an odd number of carbon atoms where the Wurtz reaction cannot be applied with the higher hydrocarbons some secondary alcohol is produced, which must be removed by repeated distillation from sodium. 

Clemmensen reduction of aldehydes and ketones. Upon reducing aldehydes or ketones with amalgamated zinc and concentrated hydrochloric acid, the main products are the hydrocarbons (>C=0 —> >CHj), but variable quantities of the secondary alcohols (in the case of ketones) and unsaturated substances are also formed. Examples are ... 

The most commonly used method for reducing an aryl ketone to an alkylbenzene employs a zinc-mercury amalgam m concentrated hydrochloric acid and is called the Clemmensen reduction Zinc is the reducing agent... 

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

The exchange of aromatic protons can be effected in the absence of any -OH or —NH2 activating group during the course of a Clemmensen reduction in deuteriochloric and deuterioacetic acid mixture (see section Ill-D). This reaction has been carried out with various tricyclic diterpenes and is best illustrated by the conversion of dehydroabietic acid into its 12,14-d2-labeled analog (40 -+ 41).Amalgamated zinc is reportedly necessary for the exchange reaction since the results are less satisfactory when a zinc chloride-mercuric chloride mixture is used. 

By application of the Clemmensen reduction,aldehydes and ketones 1 can be converted into the corresponding hydrocarbons 2. As the reducing agent zinc amalgam, together with concentrated hydrochloric acid or gaseous hydrogen chloride, is used. 

Amalgamated zinc residues isolated from Clemmensen reduction of an alkyl aryl ketone in glacial acetic acid were pyrophoric, and had to be immediately dumped into water after filtration to prevent ignition. 

Mossy zinc is activated by conversion to zinc amalgam by brief immersion in a dilute aqueous solution of mercuric chloride and decantation of the solution before the reaction proper (40 g of mossy zinc, 4g of mercuric chloride, 4 ml of concentrated hydrochloric acid and 40 ml of water [759]). This type of activation is especially used in the Clemmensen reduction which converts carbonyl groups to methylene groups [160 Procedure 31, p. 213). 

Reduction of saturated aliphatic aldehydes to alkanes was carried out by refluxing with amalgamated zinc and hydrochloric acid (Clemmensen reduction) [760, 758] (p. 28) or by heating with hydrazine and potassium hydroxide (Wolff-Kizhner reduction) [280, 759] (p. 34). Heptaldehyde gave heptane in 72% yield by the first and in 54% yield by the second method. 

Reduction of a,/3-unsaturated to saturated ketones was further achieved by electrolysis in a neutral medium using copper or lead cathodes (yields 55-75%) [766], with lithium in propylamine (yields 40-65%) [876], with potassium-graphite clathrate CgK (yields 57-85%) [807], and with zinc in acetic acid (yield 87%) [688]. Reduction with amalgamated zinc in hydrochloric acid (Clemmensen reduction) usually reduces both functions [877]. 

The Clemmensen reduction of j8-diketones (1,3-diketones) is rather complicated. The first step in the reaction of 2,4-pentanedione with zinc amalgam is an intramolecular pinacol reduction leading to a cyclopropanediol. Next the cyclopropane ring is opened in the acidic medium, and a rearrangement followed by a reduction gives the final product, a ketone, with a changed carbon skeleton [924, 925]. The ketone is usually accompanied by small amounts of the corresponding hydrocarbon [924] or an a-hydroxy ketone [925]. 

Clemmensen reduction can be effected either using amalgamated zinc or cadmium and hydrochloric acid, or in the equivalent electrochemical reaction at cathodes of cadmium or lead in 30 % sulphuric acid (see p. 344). Where the amino function is associated with a ring system, Clemmensen reduction of a-aminoketones gives rise to three types of product ... 

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. 

One procedure for the conversion of a carbonyl group to a methylene group is the Clemmensen reduction, and involves the use of zinc amalgam in the presence of concentrated hydrochloric acid. 

Clemmensen reduction. Prepare 200 g of amalgamated zinc in a 2-litre threenecked flask as detailed in Section 4.2.50, p. 467. Fit the flask with a reflux... 

Several procedures can be used to convert the carbonyl group of an aldehyde or ketone to a methylene group. One reaction, known as the Clemmensen reduction, employs amalgamated zinc (zinc plus mercury) and hydrochloric acid as the reducing agent. An example is provided by the following equation ... 

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