Bouveault-Blanc procedure

Sodium in Ethanol This is called the Bouveault-Blanc procedure and was more popular for the reduction of carboxylic esters (19-38) than of aldehydes or ketones before the discovery of LiAlH4. 

The synthesis of bufotenine itself followed closely upon the proof of its structure. Hoshino and Shimodaira reduced the ethyl ester of 5-ethoxy-indole-3-acetic acid by the Bouveault-Blanc procedure to the corresponding primary alcohol, which was treated with phosphorus tribromide and then dimethylamine, to give the ethyl ether of bufotenine, which was demethylated with aluminum chloride (130). In a later synthesis, 2,5-dimethoxybenzyl cyanide (XXIII) was alkylated by Eisleb s method with dimethylaminoethyl chloride in the presence of sodamide to give l-(2,5-dimethoxyphenyl)-3-dimethylaminopropyl cyanide (XXIV), which was then hydrogenated over Haney nickel to yield 2-(2,5-di-methoxyphenyl)-4-dimethylaminobutylamine (XXV R = Me). De-methylation of this with hydrobromic acid, followed by oxidation of the product (XXV R = H) with potassium ferricyanide yielded bufotenine (XIX) via the related quinone (109). 

Olefinic alcohols are best prepared by the action of lithium aluminum hydride on the corresponding acid or ester as in the preparation of 3-penten-l-ol (75%). The double bond may be in the a,/S-position to the ester group, The Bouveault-Blanc procedure has also been used with success for reduction of nonconjugated olefinic esters. The addition of the sodium to an alcoholic solution of the ester is superior to the reverse addition of. the ester to sodium in toluene for the preparation of 2,2-dimethyl-3-buten-l-ol (62%). Selective catalytic hydrogenation is inferior. Large amounts of catalyst are required, and the products contain saturated alcohols. ... 

Although some cyclohexadienes are readily available, many can be obtained easily by Birch reduction, which involves reduction with solutions of alkali metals in liquid ammonia, a source of solvated electrons, in the presence of alcohol as a proton source.8-10 In previous years, the Bouveault-Blanc procedure, which uses sodium metal and alcohol in liquid ammonia, was frequently employed for direct reduction of aromatic esters however, it gave rise mainly to the corresponding substituted benzoic acid.11 Rabideau et al. reported a modified procedure 12 however, in our hands, this resulted in the reduction of the ester function to give benzoic acid. We have found that the Birch reduction of benzoic acid, followed by esterification, is an efficient procedure for the preparation of the corresponding 1,4-dihydro compound prior to the coordination of the arene to produce functionalized dimeric ruthenium-arene complexes.13... 

Small portions of Na added to a rapidly stirred soln. of trans-fi-(2-csitbo-methoxycyclohexane) propionic acid in liq. NHg and abs. ethanol, a little more ethanol finally added to decompose remaining Na, stirring continued until most of the NHg has evaporated, water added, acidified with HCl, extracted with ether, and the resulting crude hydroxy acid distilled in vacuo crude trans-3-oxa-4-oxobicyclo[5.4.0]undecane. Y 71.7%.— The above selective reduction method is superior to the Bouveault-Blanc procedure and nearly theoretical quantities of the hydroxy acid have been obtained. L. A. Paquette and N. A. Nelson, J. Org. Chem. 27, 2272 (1962). 

Na added all at once with vigorous stirring and some initial cooling to a mixture of ethyl hydrocinnamate, ethanol, phenol, and some quinoline, heated in an oil bath at 150°, then the temp, raised to 170° until the Na has disappeared after 15 min. phenylpropyl alcohol. Y 90%.—Similarly at 170-230° Ethyl L-leucinate —leucinol. Y 67%.—This method gives higher yields of amino-alcohols from amino esters with unprotected amino groups than the original Bouveault-Blanc procedure. F. e., also without addition of quinoline, s. W. Enz,. Helv. U, 206 (1961). 

Optically active esters in which the activity is due to asymmetry of the a-carbon atom ate racemized by the Bouveault-Blanc and catalytic hydrogenation procedures. The optically active alcohols may be prepared by the addition of small pieces of sodium to a stirred mixture of an ethereal solution of the ester and aqueous sodium acetate at 0°. A slight acidity is maintained by periodic additions of acetic acid (Prin s method).An asymmetric center in the alpha position to a carboxyl group is not racemized by lithium aluminum hydride. ... 

The reduction of esters by sodium and alcohol (Bouveault-Blanc) is widely used. An alcoholic solution of the ester is added to a large excess of sodium under benzene or toluene. The use of absolute alcohol is essential otherwise an appreciable quantity of acid is produced by saponification. Straight-chain primary alcohols containing up to thirty-five carbon atoms have been made by the reduction of the corresponding esters with sodium sand and n-butyl alcohol. An improved technique based on the mechanism of the reaction is described. By this procedure a xylene solution of the ester and the reducing alcohol is added to molten... 

Both the Bouveault-Blanc and catalytic hydrogenation proceduresare popular methods for the preparation d dials from esters of dibasic acids. The reduction of malonic esters, /3-keto esters, and /3-hydroxy esters by the usual catalytic hydrogenation procedure results in extensive bydrogenolysis of the carbon chain to give lower-molecular-weight alcohols. However, with relatively large amounts of catalyst... 

Alcohols from carboxylic acid esters Bouveault-Blanc reduction s. 1, 64, 75 2, 89/90 new procedures s. 3, 49/50 also amines from nitriles s. 4, 89 Preparation of anhydrous alcohols s. 4,90 Alcohols from ethylenecarboxylic acid esters s. 4, 91 Hydroxyacetals from carbalkoxyacetals s. 4, 92 Acridines from acridones s. 2, 91 COOR -V CH2OH... 

Classical reducing agents are known generally to be ineffective in the reduction of sulphones . Thus, although the procedure of Bouveault and Blanc has been used... 

The reduction of carboxylic esters by sodium and alcohol, discovered by Bouveault and Blanc in 1903, is carried out under very drastic conditions.519 The usual procedure is to drop one mole of the ester in absolute alcohol directly on to six gram-atoms of sodium lumps and then to heat the mixture until all the sodium is dissolved, this requiring several hours under reflux. The whole is treated with water and worked up for the alcohol produced. 

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