Clemmensen reduction keto acids

Reduction of the keto group in keto acids to a methylene group was accomplished by means of Clemmensen reduction. 4-Phenyl-4-oxobutanoic acid, on... 

Trimethylcyclopentanone has been prepared by the oxidation of 1-hydroxy-2,4,4-trimethylcyclopentanecarboxylic acid with lead dioxide in sulfuric acid,3 by the hydrogenation of 2,4,4-trimethyl-2-cyc.lopentenone, 4 5 by the Clemmensen reduction of dimethyldihydroresorcinol,6 7 by the distillation of powdered 2,4,4-trimethyladipic acid with sodium hydroxide,8 and by the saponification and decarboxylation of ethyl 2-keto-l,4,4-tri-mcthylcylopentanecarboxylate.9 10 The rearrangement of iso-phorone oxide 11 appears to represent the optimum combination of favorable yield and convenient procedure. 

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). 

Catalytic hydrogenation over palladium-on-charcoal with perchloric acid promoter is more satisfactory than the Clemmensen method for the reduction of a-phenyl-/3-benzoylpropionic acid to a,y-diphenylbutyric acid (83%). Several other keto acids have been successfully hydrogenated over this catalyst. ... 

A modified Wolff-Kishner reduction employing hydrazine in glycol has been used to prepare 10-phenyldecanoic acid from the 10-keto acid (70%) and palmitic acid labeled with C14 at carbon atom 6 from the corresponding 5-keto acid. As in the Clemmensen reduction, the thiophene nucleus is unaffected. ... 

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

In the laboratory of K. Krohn, the total synthesis of phytoalexine (+)-lacinilene C methyl ether was completed. In order to prepare the core of the natural product, an intermolecular Friedel-Crafts acylation was carried out between succinic anhydride and an aromatic substrate, followed by an intramolecular acylation. After the first acylation, the 4-keto arylbutyric acid was reduced under Clemmensen reduction conditions (to activate the aromatic ring for the intramolecular acylation). 

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. 

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