Clemmensen reduction aromatic ketones

Unsaturated hydrocarbons are present in nearly all products of the Clemmensen reduction of aromatic ketones and must be removed, if the hydrocarbon is requiral pure, by the above process. Secondary alcohols, often produced m small amount are not appreciably steam-volatile. 

However, most frequently used methods for reduction of aromatic ketones to hydrocarbons are, as in the case of other ketones, Clemmensen reduction [160, 161, 758, 843, 844] Procedure 31, p. 213), Wolff-Kizhner reduction [280,281,282, 759, 774,845] Procedure 45, p. 216), or reduction of p-toluene-sulfonylhydrazones of the ketones with lithium aluminum hydride [811, 812] or with borane and benzoic acid [786]. 

The reduction of ketones to alkanes can also be done by the Clemmensen reduction using zinc and HC1. This reaction is specific for aromatic ketones, however. 

The reduction of aldehydes and ketones. Aromatic hydrocarbons are the main products when aromatic aldehydes or ketones are reduced with amalgamated zinc and concentrated hydrochloric acid (the Clemmensen reduction, e.g. hexylbenzene, Expt 6.3). 

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-type reduction.1 Aromatic ketones can be reduced to the corresponding methylene compounds with ammonium formate on transfer hydrogenation in acetic acid catalyzed by 10% Pd/C. The reduction is usually complete in 10-30 minutes at 110°. Halo and nitro substituents can be reduced under these conditions, and a,p-unsaturated carbonyl groups are reduced to saturated carbonyl groups. 

The reduction of the carbonyl group of an aromatic ketone to a methylene group can also be accomplished by catalytic hydrogenation. An example of this method is shown in the following equation. Note that the carbonyl group in this reaction must be attached directly to the aromatic ring. The Clemmensen and Wolff-Kishner reductions do not have this restriction. 

Many reactions are not affected by the presence of a nearby benzene ring yet others depend on the aromatic ring to promote the reaction. For example, the Clemmensen reduction is occasionally used to reduce aliphatic ketones to alkanes, but it works best reducing aryl ketones to alkylbenzenes. Several additional side-chain reactions show the effects of a nearby aromatic ring. 

Reduction of alkyl aryl ketones. Aromatic ketones can be reduced to the corresponding hydrocarbons by reaction with LiAlH4 and P2I4 in refluxing benzene. The ketone and the two reagents are used in equimolar amounts. Yields range from 45 to —100%. The method offers a mild alternative to Clemmensen and Wolff-Kishner reductions. 

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)." ... 

Talapatra, S. K., Chakrabarti, S., Mallik, A. K., Talapatra, B. Some newer aspects of Clemmensen reduction of aromatic ketones. Tetrahedron 1990, 46, 6047-6052. 

Fig. (15). The ketone (173) from the unsaturated alcohol (23) is converted to the tricyclic ketone (175) by standard organic reactions. It is made to react with acetone to obtain the compound (176). This on dehydration followed by aromatization yielded the compound (178), which on demethoxylation, oxidation and methylation produces the ketone (179) whose transformation to taxodione (180) has been accomplished by Japanese workers. The Clemmensen reduction of the ketone (179) followed by oxidation and demethoxylation produces sugiol (181).

Clemmensen reduction involving reaction of ketones with amalgamated zinc in the presence of hydrochloric acid is one of the classical methods of deoxygenation . It works well with aromatic ketones but its applicability to alicyclic systems is severely limited. The strongly acidic conditions and high temperature make this procedure too stringent, especially if other functional groups are present. Quite often side reactions are observed and complex mixtures of products are obtained. Nonetheless, the method has found favour in many cases (equation 60) ... 

When cyclic anhydrides are used as one component, the Friedel-Crafts acylation provides a means of adding a new ring to an aromatic compound. One illustration is shown here. Note that only the ketone is reduced in the Clemmensen reduction step. The carboxylic acid is unaffected. The same result can be achieved using the Wolff-Kishner reduction. 

Aryl ketones may be reduced to hydrocarbons by the Clemmensen reduction using zinc amalgam and HCI or by catalytic hydrogenolysis in the presence of palladium metal. Dissolving metal reduction of aromatic rings using an alkali metal in liquid ammonia gives 1,4-hexadienes. 

Clemmensen reaction. The Clemmensen method of reduction (1913) consists in refluxing a ketone with amalgamated zinc and hydrochloric acid. Acetophenone, for example, is reduced to ethylbenzene. The method is applicable to the reduction of most aromatic-aliphatic ketones to at least some aliphatic and alicyclic ketones, to the y-keto acids obtainable by Friedel-Crafts condensations with succinic anhydride (succinolylation), and to the cyclic ketones formed by intramolecular condensation. 

Haworth phenanthrene synthesis. Acylation of aromatic compounds with aliphatic dibasic acid anhydrides to (i-aroylpropionic acids, reduction of the carbonyl group according to Clemmensen or Wolff-Kishner procedures, cyclization of the y-arylbutyric acid with 85% sulfuric acid, and conversion of the cyclic ketone to polycyclic hydroaromatic and subsequently to aromatic compounds. 

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