Hydrogenation carbonyl compound reduction

A variation of the classical reductive amination procedure uses sodium cyanoboro hydride (NaBH3CN) instead of hydrogen as the reducing agent and is better suited to amine syntheses m which only a few grams of material are needed All that is required IS to add sodium cyanoborohydride to an alcohol solution of the carbonyl compound and an amine... 

Study of the mechanism of this complex reduction-Hquefaction suggests that part of the mechanism involves formate production from carbonate, dehydration of the vicinal hydroxyl groups in the ceUulosic feed to carbonyl compounds via enols, reduction of the carbonyl group to an alcohol by formate and water, and regeneration of formate (46). In view of the complex nature of the reactants and products, it is likely that a complete understanding of all of the chemical reactions that occur will not be developed. However, the Hquefaction mechanism probably involves catalytic hydrogenation because carbon monoxide would be expected to form at least some hydrogen by the water-gas shift reaction. 

High yields of optically active cyanohydrins have been prepared from hydrogen cyanide and carbonyl compounds using an enzyme as catalyst. Reduction of these optically active cyanohydrins with lithium aluminum hydride in ether affords the corresponding substituted, optically active ethanolamine (5) (see Alkanolamines). 

With certain carbonyl compounds, however, such as 3-keto steroids, the isotopic composition is poor due to the rapid exchange of the activated a-hydrogens in the substrate prior to reduction. The corresponding alcohols, in their thermodynamically more stable configuration, are usually found as... 

Reduction of unsaturated carbonyl compounds to the saturated carbonyl is achieved readily and in high yield. Over palladium the reduction will come to a near halt except under vigorous conditions (73). If an aryl carbonyl compound, or a vinylogous aryl carbonyl, such as in cinnamaldehyde is employed, some reduction of the carbonyl may occur as well. Carbonyl reduction can be diminished or stopped completely by addition of small amounts of potassium acetate (i5) to palladium catalysts. Other effective inhibitors are ferrous salts, such asferroussulfate, at a level of about one atom of iron per atom of palladium. The ferrous salt can be simply added to the hydrogenation solution (94). Homogeneous catalysts are not very effective in hydrogenation of unsaturated aldehydes because of the tendencies of these catalysts to promote decarbonylation. 

Ruthenium is excellent for hydrogenation of aliphatic carbonyl compounds (92), and it, as well as nickel, is used industrially for conversion of glucose to sorbitol (14,15,29,75,100). Nickel usually requires vigorous conditions unless large amounts of catalyst are used (11,20,27,37,60), or the catalyst is very active, such as W-6 Raney nickel (6). Copper chromite is always used at elevated temperatures and pressures and may be useful if aromatic-ring saturation is to be avoided. Rhodium has given excellent results under mild conditions when other catalysts have failed (4,5,66). It is useful in reduction of aliphatic carbonyls in molecules susceptible to hydrogenolysis. 

Some workers allow the amine and carbonyl compound to stand together some time before hydrogenation (i,59), but this procedure is not always necessary nor even desirable (ii). The delay technique is illustrated by reductive alkylation of ethyl-4-aminocyclohexane carboxylate (4) with benzaldehyde to S, a route that permitted an important improvement in the production of isoquinuclidine (8) (59). 

Azines can be reduced catalytically to the disubstituted hydrazines (24,51) and then to the amine if the reduction is continued (108). The hydrogenolysis chemistry is thus that of hydrazines. The hydrazine can be formed in situ by hydrogenation of a mixture of hydrazine and 2 mol of carbonyl compound... 

Alkenes are reduced by addition of H2 in the presence of a catalyst such as platinum or palladium to yield alkanes, a process called catalytic hydrogenation. Alkenes are also oxidized by reaction with a peroxyacid to give epoxides, which can be converted into lTans-l,2-diols by acid-catalyzed epoxide hydrolysis. The corresponding cis-l,2-diols can be made directly from alkenes by hydroxylation with 0s04. Alkenes can also be cleaved to produce carbonyl compounds by reaction with ozone, followed by reduction with zinc metal. 

The direct reductive amination (DRA) is a useful method for the synthesis of amino derivatives from carbonyl compounds, amines, and H2. Precious-metal (Ru [130-132], Rh [133-137], Ir [138-142], Pd [143]) catalyzed reactions are well known to date. The first Fe-catalyzed DRA reaction was reported by Bhanage and coworkers in 2008 (Scheme 42) [144]. Although the reaction conditions are not mild (high temperature, moderate H2 pressure), the hydrogenation of imines and/or enam-ines, which are generated by reaction of organic carbonyl compounds with amines, produces various substituted aryl and/or alkyl amines. A dihydrogen or dihydride iron complex was proposed as a reactive intermediate within the catalytic cycle. 

The catalytic hydrosi(ly)lations of other C=X functional groups (X = O, NR) constitute alternative routes to the reduction of aldehydes, ketones, imines and other carbonyl compounds (Scheme 2.9), circumventing the use of molecular hydrogen or occasionally harsh transfer hydrogenation conditions. 

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