Reduction of carboxylic acid esters

Reduction of Carboxylic Acids, Esters, and Anhydrides to Aldehydes ... 

Hydrolysis of enol esters 0-83 Reduction of acyl halides 0-84 Reduction of carboxylic acids, esters, or anhydrides 0-85 Reduction of amides 0-95 Alkylation and hydrolysis of imines, alkylation of aldehydes 0-97 Alkylation and hydrolysis of dithi-anes... 

Selective dehalogenation of halopyridines is an important industrial process for the same reason that reduction of carboxylic acids, esters, amides, and nitriles are also important. There is a dearth of selective oxidation technologies whether by conventional or electrochemical methods. Therefore, many intermediate oxidation stage products are made by overoxidation, i.e., overhalogenation, followed by selective reduction. 

Fig. 17.62. Two-step reduction of carboxylic acid esters to ethers. In the first step, a reduction via hydride transfer occurs and leads to a tetrahedral intermediate that is stable enough to be acylated to the (alpha))-acetoxyether A. The second step involves a so-called "ionic reduction"...

There is no generally useful nonhydride method for the direct reduction of carboxylic acid esters to aldehydes. There are, however, procedures which are valuable under particular circumstances. An important example is the one-electron reduction of aldonolactones to aldoses. Two factors presumably contribute to the success of these reactions firstly the presence of electron-withdrawing substituents in the substrates, raising the reactivity of the carbonyl group, and secondly the ability of the products to form cyclic hemiacetals stable to further reduction. 

Reduction. The reagent is useful for reduction of carboxylic acid esters to primary alcohols. For example, the following esters have been reduced to the corresponding carbinols ethyl p-nitrobenzoate (96% yield), ethyl phenylacetate (90% yield), ethyl gly-cinate (70% yield). The reaction has some useful features Hydroxylic solvents (ethanol, water) can be used, the selectivity is higher than in the case of lithium aluminum hydride, and the reagent is nearly neutral. The reagent was found to be satisfactory for reduction of the dimethyl ester of 4,4 -dinitro-2,2 -diphenic acid (la) to the corresponding alcohol (lb, 51%yield).2... 

Reduction of carboxylic acid esters. Esters are not reduced by sodium borohydride. However, if ethanedithiol is added (excess), most benzoate esters are reduced to benzyl alcohols in high yield. Thiophenol and ethylmercaptan do not share this property. Several aliphatic esters are also reduced by NaBH4 activated by HSCHjCHjSH. ... 

Alcohols from oxo compds. 20 eqs. NaBH4 added to a soln. of 5 eqs. ZrC in THF at room temp, under N2, a soln. of 4 eqs. acetophenone in the same solvent added, and the mixture stirred at room temp, for 5 h - 1-phenylethanol. Y 96%. ZrCl4 is inexpensive, easy to use, and does not affect ar. nitro compds. and bromides. F.e., also reduction of carboxylic acids, esters and halides to prim, alcohols, and amides, oximes, alkoximes, nitriles, and imines to amines, s. S. Itsuno et al.. Synthesis 1988, 995-6. 

Reduction of Carboxylic Acid Esters, Amides and Nitriles... 

Lithium aluminium hydride, LiAlH, is a very active reducing agent, and is used particularly for the ready reduction of carboxylic acids (or their esters) to primary alcohols R-COOH -> R CH,OH. 

PREPARATION OF ALCOHOLS BY REDUCTION OF CARBOXYLIC ACIDS AND ESTERS... 

Section 15.3 Alcohols can be prepared from carbonyl compounds by reduction of carboxylic acids and esters. See Table 15.3. 

The aldehyde intermediate can be isolated if 1 equivalent of diisobutvl-aluminum hydride (D1BAH) is used as the reducing agent instead of LiAlH4. The reaction has to be carried out at -78 °C to avoid further reduction to the alcohol. Such partial reductions of carboxylic acid derivatives to aldehydes also occur in numerous biological pathways, although the substrate is either a thioester or acyl phosphate rather than an ester. 

Reduction of carboxylic acids and esters, aldehydes, and nitriles, and the hydro-boration of alkenes with diborane in non-ethereal solvents is highly effective (Table 11.8), but reduction of nitro groups or cleavage of arena-halogen bonds does not occur [1]. However, in spite of the potential advantages, very little use appears to have been made of the procedure. 

The reduction of carboxylic acids or esters requires very powerful reducing agents such as lithium aluminum hydride (LiAlH,) or sodium (Na) metal. Aldehydes and ketones are easier to reduce, so they can use sodium borohy-dride (NaBH,j). Examples of these reductions are shown in Figure 3-13. 

Reduction of Carboxylic Acids and Esters to Alkanes Trihydro-de-alkoxy,oxo-tersubstitution, etc. 

Reduction of carboxylic acids 9-42 Reduction of carboxylic esters 9-43 Reduction of carboxylic esters with titanocene dichloride 9-44 Reduction of anhydrides 9-45 Reduction of acyl halides 9-53 Reduction of nitriles 9-57 Reduction of hydroperoxides 9-60 Reduction of peroxides 9-69 Reaction between aldehydes and base (Cannizzaro)... 

An important example of this type of reaction is the formation of esters, which was discussed previously in connection with the reactions of alcohols in Section 15-4D. Similar addition-elimination mechanisms occur in many reactions at the carbonyl groups of acid derivatives. A less obvious example of addition to carboxyl groups involves hydride ion (H 0) and takes place in lithium aluminum hydride reduction of carboxylic acids (Sections 16-4E and 18-3C). 

Functional Group Transformation Alcohols can be prepared by nucleophilic substitution of alkyl halides, hydrolysis of esters, reduction of carboxylic acids or esters, reduction of aldehydes or ketones, electrophilic addition of alkenes, hydroboration of alkenes, or substitution of ethers. 

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