Bouveault-Blanc reduction esters

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... 

Bouveault-Blanc reduction The reduction of esters to alcohols by nascent hydrogen gen-... 

This is an example of the reduction of an ester of a dibasic acid to the corre spending glycol (Bouveault-Blanc reduction) ... 

Benzilic acid rearrangement Benzoin reaction (condensation) Blanc chloromethylation reaction Bouveault-Blanc reduction Bucherer hydantoin synthesis Bucherer reaction Cannizzaro reaction Claisen aldoi condensation Claisen condensation Claisen-Schmidt reaction. Clemmensen reduction Darzens glycidic ester condensation Diazoamino-aminoazo rearrangement Dieckmann reaction Diels-Alder reaction Doebner reaction Erlenmeyer azlactone synthesis Fischer indole synthesis Fischer-Speior esterification Friedel-Crafts reaction... 

Naturally occurring fatty alcohols used in the fragrance industry are produced principally by reduction of the methyl esters of the corresponding carboxylic acids, which are obtained by transesterification of natural fats and oils with methanol. Industrial reduction processes include catalytic hydrogenation in the presence of copper-chromium oxide catalysts (Adkins catalysts) and reduction with sodium (Bouveault—Blanc reduction). Unsaturated alcohols can also be prepared by the latter method. Numerous alcohols used in flavor compositions are, meantime, produced by biotechnological processes [11]. Alcohols are starting materials for aldehydes and esters. 

Primary alcohols may be conveniently prepared by the reduction of esters with sodium and absolute ethanol (the Bouveault-Blanc reduction, Expt 5.37). 

If the reaction is carried out in the presence of a proton donor, such as alcohol, simple reduction of the ester to the alcohol takes place (Bouveault-Blanc Reduction). 

This important fragrance material probably was introduced in commercial perfumery during the first decade of the twentieth century with the discovery of the Bouveault-Blanc reduction of esters by sodium and an alcohol (10). This is the first of several methods of preparation shown in Figure 16. Large quantities of phenylethyl alcohol were made by sodium reduction of butyl phenylacetate in normal butanol. The basic raw materials were readily available at low cost from benzyl chloride, sodium cyanide and fermentation butanol. 

The mechanism of the Bouveault-Blanc reduction is shown in rows 1 and 2 of Figure 17.59. It starts with the sequence ester —t radical anion C —> hydroxylated radical... 

Fig. 17.59. Reduction of a carboxylic ester with dissolving sodium. Branching of the reduction paths in the presence (Bouveault-Blanc reduction) and absence (acyloin condensation) of protons.

The mechanism of the Bouveault-Blanc reduction is shown in rows 1 and 2 of Figure 14.51. It starts with the sequence ester — radical anion C —> hydroxylated radical D —> hydroxylated organosodium compound B — hemiacetal anion A. This sequence is completely analogous to the sequence ketone — ketyl —> hydrox-ylated radical A —> hydroxylated organosodium compound B — sodium alkoxide that occurs in the reduction of a ketone with Na in iPrOH (Figure 14.46). 

The so-called acyloin condensation consists of the reduction of esters—and the reduction of diesters in particular—with sodium in xylene. The reaction mechanism of this condensation is shown in rows 2-4 of Figure 14.51. Only the first of these intermediates, radical anion C, occurs as an intermediate in the Bouveault-Blanc reduction as well. In xylene, of course, the radical anion C cannot be protonated. As a consequence, it persists until the second ester also has taken up an electron while forming the bis(radical anion) F. The two radical centers of F combine in the next step to give the sodium glycolate G. Compound G, the dianion of a bis(hemiacetal), is converted into the 1,2-diketone J by elimination of two equivalents of sodium alkoxide. This diketone is converted by two successive electron transfer reactions into the enediolate I, which is stable in xylene until it is converted into the enediol H during acidic aqueous workup. This enediol tautomerizes subsequently to furnish the a-hydroxyketone—or... 

Fatty alcohols are obtained by direct hydrogenation of fatty acids or by hydrogenation of fatty acid esters. Typically, this is performed over copper catalysts at elevated temperature (170°C-270°C) and pressure (40-300 bar hydrogen) [26], By this route, completely saturated fatty alcohols are produced. In the past, unsaturated fatty alcohols were produced via hydrolysis of whale oil (a natural wax occurring in whale blubber) or by reduction of waxes with sodium (Bouveault-Blanc reduction). Today, they can be obtained by selective hydrogenation at even higher temperatures (250°C-280°C), but lower pressure up to 25 bar over metal oxides (zinc oxide, chromium oxide, iron oxide, or cadmium oxide) or partially deactivated copper chromite catalysts [26],... 

When a proton source such as ethanol is used, sodium reduces esters, aldehydes and ketones to alcohols and the reduction is known as Bouveault-Blanc reduction s . But metal hydride reduction of carbonyl compounds gives higher yields of alcohols. 

Alcohols will form metal salts. Thus treatment with sodium, potassium or magnesium leads to the evolution of hydrogen and the formation of the alkoxides (Scheme 2.11b). The liberation of hydrogen in this reaction is used in the Bouveault-Blanc reduction of ketones, esters and nitro compounds. 

The desirable fragmentation (A) to give the alkyl radical represents a viable method for overall deoxygenation, providing that alternative processes involving O—X fission (B), or H-abstraction (C) or net two-electron reduction (D the Bouveault-Blanc reduction of esters, for example) followed by O— fission, can be minimized. Conditions have been established which cause (A) to be the dominant process for X = C, P and S this section will compare the merits of these processes for alcohol deoxygenation. 

Addition of Sodium to Esters. When sodium is added to esters, different products are obtained, depending upon the solvents employed. In alcohol solution the Bouveault-Blanc reduction occurs and an alcohol is formed. In an inert solvent such as ether, acyloins are produced. These reactions are closely related and will be considered together. 

BOUVEAULT-BLANC Reduction Reduction of esters to alcohols by means of sodium in alcohol (see 1st edition). 

In ester condensations it is sometimes necessary to warm the mixture gently to overcome an induction period, but cooling is often required as the reaction proceeds, otherwise side reactions may occur, e.g., Bouveault-Blanc reduction (see page 76). It is not always easy or possible to determine the end of the reaction from the appearance of precipitated solids, because the sodium may become coated mechanically and withdrawn from the reaction. Care is thus needed during working up, which usually begins with acidification of the reaction mixture when possible, the acetic acid used for acidification should not be added to the reaction flask, but the reaction mixture should be poured into a wide, open porcelain dish and the larger pieces of sodium should be then removed by hand. 

It has however long been known sodium in ethanol effects "dissolving metal reductions", such as the classical Bouveault-Blanc reduction of carboxylic esters to alcohols, in good yields ... 

Alcohols from carboxylic acid esters Modified Bouveault-Blanc reduction... 

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. 

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