Reduction of Aldehydes and Ketones to Alcohols

Catalytic hydrogenation of both aromatic and aliphatic aldehydes and ketones with hydrogen gas (H2) over platinum (Pt) and nickel (Ni) catalysts to produce the cor- 

Methyl phenyl ketone (acetophenone, C6H5COCH3) can be reduced to 1-phenylethanol [C6HsCH(OH)CH3], Equation 9.14, under the same conditions (in ethanol, CH3CH2OH, solvent) in 2.5 h. However, with a platinum (Pt) catalyst in ethanoic acid (acetic acid, CH3CO2H), the reduction of methyl phenyl ketone (acetophenone, C6H5COCH3) is very fast and most of the product is phenylethane, hydrogenolysis having occured (Equation 9.15). 

These complex hydrides balance basicity with nucleophilicity, and the counterions (e.g., LT) or the hydride itself (e.g., BH3) strongly coordinate with the oxygen of the carbonyl so that addition of hydride (H ) to the carbon of the carbonyl is preferred to proton abstraction from the carbon a to the carbonyl. Indeed, the simpler hydrides such as sodium hydride (NaH) are generally too basic to affect reduction. Thus, the simpler hydrides are used for proton abstraction to produce enolate anions, while the complex hydrides are used for reduction. 

Further, the development of a multitude of methods based on these families of compounds has been rapid because reduction of one functional group in the presence of another is often a major synthetic challenge and the different reagents can 

Given the observation that all of these reagents are capable of, at least, reducing aldehydes and ketones, a variety of investigations have been undertaken to study how changes in the structure of the carbonyl compound and the nature of the solvent affect the outcome of the reaction. 

In Chapter 5, we saw that hydrogen gas can reduce carbon-carbon double bonds in the presence of a nickel, palladium, or platinum catalyst. In Chapter 15, we learned that hydrogen gas can reduce aldehydes and ketones to alcohols in the presence of Raney nickel. However, this type of reduction requires more severe conditions than those required to reduce alkenes. We also learned that both lithium aluminum hydride (LiAlH4) and sodium borohydride (NaBH4) reduce carbonyl groups, but that neither reagent reduces carbon—carbon double nor triple bonds. 

Because neither lithium aluminum hydride nor sodium borohydride reacts with alkenes or alkynes, these reagents selectively reduce a carbonyl group in compounds with carbon—carbon multiple bonds. 

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Addition of sodium dithionite to formaldehyde yields the sodium salt of hydroxymethanesulfinic acid [79-25-4] H0CH2S02Na, which retains the useful reducing character of the sodium dithionite although somewhat attenuated in reactivity. The most important organic chemistry of sodium dithionite involves its use in reducing dyes, eg, anthraquinone vat dyes, sulfur dyes, and indigo, to their soluble leuco forms (see Dyes, anthraquinone). Dithionite can reduce various chromophores that are not reduced by sulfite. Dithionite can be used for the reduction of aldehydes and ketones to alcohols (348). Quantitative studies have been made of the reduction potential of dithionite as a function of pH and the concentration of other salts (349,350). 

Reduction of Aldehydes and Ketones to Alcohols C,0-Dihydro-addition... 

The simplest large-scale procedure for reduction of aldehydes and ketones to alcohols is by catalytic hydrogenation ... 

The non-microsomal oxidation is catalysed by enzymes that are free in the cellular plasma or by relatively non-specific enzymes present in the mitochondrial fraction of the homogenized tissue of liver cells. Two of these enzymes which are particularly important are monoaminooxidase, catalysing the metabolism of primary amines and controlling the level of biogenic amines, and diaminooxidase, catalysing selectively the oxidation of one out of two amino groups of diamines. Aliphatic alcohols are oxidized by the alcohol dehydrogenase to aldehydes. This reaction is reversible and the same enzyme participates in the reduction of aldehydes and ketones to alcohols [7]. 

Used with permission from Naimi-Jamal MR, Mokhtari J, Dekamin MG, Kaupp G. Sodium tetraalkoxyborates intermediates for the quantitative reduction of aldehydes and ketones to alcohols through ball milling with NaBH4. Eur J Org Chem 2009 3567-72. 

For the reduction of aldehydes and ketones to alcohols, biological systems use NADH, a reagent whose results are equivalent to laboratory hydride reducing agents. As an example, the final step in alcoholic fermentation— the... 

Lactonization Isomerization Oxidation of alcohols to aldehydes ketones Reduction of aldehydes and ketones to alcohols Oxidation of amino groups to nitro groups Hydrolysis of nitriles to amides and caibo Q lic acids Functional group alteration... 

In biological systems, alcohols are metabolized by oxidation to carbonyl compounds. For example, ethanol is converted into acetaldehyde by the cationic oxidizing agent nicotinamide adenine dinucleotide (abbreviated as NAD see Real Life 25-2). The process is catalyzed by the enzyme alcohol dehydrogenase. (This enzyme also catalyzes the reverse process, reduction of aldehydes and ketones to alcohols see Problems 58 and 59 at the end of this chapter.) When the two enantiomers of 1-deuterioethanol are subjected... 

Sodium borohydride adsorbed on alumina is a new reagent combination for the reduction of aldehydes and ketones to alcohols in aprotic solvents such as ether. Cyanoborohydride anion, [BHsCN] , supported on an anion-exchange resin containing quaternary ammonium groups has been found in preliminary results to be a successful and convenient reagent for, inter alia, the reduction of enones to allylic alcohols. Ease of work-up and retention of cyanide by the resin are obvious advantages. Carbonyl compounds can also be reduced to alcohols by tributyltin hydride in a cyclohexane-silica gel slurry aldehydes are selectively reduced in the presence of ketones and products are obtained by simple elution from the silica. Adsorption, and consequent polarization, of the carbonyl group by the silica seems to be important in the mechanism of this mild, non-basic, process. 

Poly(methylhydroxiloxane) (PMHS) serves as the hydride source for reduction of aldehydes and ketones to alcohols with 2 mol % of the catalyst bis(dibutylacetoxytin) oxide, thus avoiding large quantities of toxic organotin hydrides. PMHS in the presence of Pd-on-charcoal in ethanol also reduces nitrobenzene to aniline, benzaldehyde to toluene, 1-alkenes to alkanes, and only the cis isomer of an isomeric mixture of 2-nonenes to nonane. 

Reductions of aldehydes and ketones to alcohols proceed at slower rates with AERs in BH4 form than with NaBH4 in ethanol.a,j8-Unsaturated carbonyl compounds are reduced by BH4 in a gel AER to the allylic alcohols. Cyanoborohydride ion in a macroporous AER effects reductive aminations of ketones and ammonia to primary amines, reductive methylations of primary amines to the N,iV-dimethyl tertiary amines with aqueous formaldehyde, reductions of N-alkyl- and AT-acyl-pyridinium ions to tetrahydropyridines, and reductions of primary alkyl halides to alkanes. Nitroarenes are reduced to amines, the bromide of a-bromocarbonyl compounds is replaced by hydride, and 1,2-dibromoalkanes give alkenes by treatment with HFe(CO)4 in a macroporous AER. 

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