Oxidation alcohols and aldehydes

Non-microsomal oxidations may be subdivided into amine oxidation, alcohol and aldehyde oxidation, dehalogenation, purine oxidation, and aromatization. 

Alcohol and aldehyde oxidation. Although a microsomal enzyme system has been demonstrated, which oxidizes ethanol (see above), probably the more important enzyme in vivo is alcohol dehydrogenase, which is a cytosolic enzyme (soluble fraction) and is found in the liver and also in the kidney and the lung. 

Aldehydes and ketones show expected behavior. Metal hydride reductions yield the corresponding alcohols and aldehyde oxidations furnish the corresponding acids. 

Alcohol and Aldehyde Oxidations Primary alcohols are oxidized to their respective aldehydes, which can be further oxidized to carboxylic acids. Secondary alcohols can be oxidized to ketones. Some diols and ketones can undergo oxidative C—C bond cleavage ... 

The standard redox potentials of inorganic oxidants used in organic synthesis are generally around or above + 1.0 V. Organic substrates do not have such high potentials. The values for the CH4/CH3OH and CjHj/CjHjOH couples are at +0,59 V and 0.52 V, respectively. The oxidation of alcohols and aldehydes corresponds to values around 0.0 V (W.M. 

The conversion of primary alcohols and aldehydes into carboxylic acids is generally possible with all strong oxidants. Silver(II) oxide in THF/water is particularly useful as a neutral oxidant (E.J. Corey, 1968 A). The direct conversion of primary alcohols into carboxylic esters is achieved with MnOj in the presence of hydrogen cyanide and alcohols (E.J. Corey, 1968 A,D). The remarkably smooth oxidation of ethers to esters by ruthenium tetroxide has been employed quite often (D.G. Lee, 1973). Dibutyl ether affords butyl butanoate, and tetra-hydrofuran yields butyrolactone almost quantitatively. More complex educts also give acceptable yields (M.E. Wolff, 1963). 

Eigure 2 shows that even materials which are rather resistant to oxidation ( 2/ 1 0.1) are consumed to a noticeable degree at high conversions. Also the use of plug-flow or batch reactors can offer a measurable improvement in efficiencies in comparison with back-mixed reactors. Intermediates that cooxidize about as readily as the feed hydrocarbon (eg, ketones with similar stmcture) can be produced in perhaps reasonable efficiencies but, except at very low conversions, are subject to considerable loss through oxidation. They may be suitable coproducts if they are also precursors to more oxidation-resistant desirable materials. Intermediates which oxidize relatively rapidly (/ 2 / i — 3-50 eg, alcohols and aldehydes) are difficult to produce in appreciable amounts, even in batch or plug-flow reactors. Indeed, for = 50, to isolate 90% or more of the intermediate made, the conversion must... 

Autooxidation. Liquid-phase oxidation of hydrocarbons, alcohols, and aldehydes by oxygen produces chemiluminescence in quantum yields of 10 to 10 ° ein/mol (128—130). Although the efficiency is low, the chemiluminescent reaction is important because it provides an easy tool for study of the kinetics and properties of autooxidation reactions including industrially important processes (128,131). The light is derived from combination of peroxyl radicals (132), which are primarily responsible for the propagation and termination of the autooxidation chain reaction. The chemiluminescent termination step for secondary peroxy radicals is as follows ... 

Aldehyde oxidations occur through intermediate l/l-diols, or hydrates, which are formed by a reversible nucleophilic addition of water to the carbonyl group. Even though formed to only a small extent at equilibrium, the hydrate reacts like any typical primary or secondary alcohol and is oxidized to a carbonyl compound (Section 17.7). 

Much of the chemistry of monosaccharides is the familiar chemistry of alcohols and aldehydes/ketones. Thus, the hydroxyl groups of carbohydrates form esters and ethers. The carbonyl group of a monosaccharide can be reduced with NaBH4 to form an alditol, oxidized with aqueous Br2 to form an aldonic acid, oxidized with HNO3 to form an aldaric acid, oxidized enzymatically to form a uronic acid, or treated with an alcohol in the presence of acid to form a glycoside. Monosaccharides can also be chain-lengthened by the multistep Kiliani-Fischer synthesis and can be chain-shortened by the Wohl degradation. 

Carboxylic acids can be prepared by oxidizing primary alcohols and aldehydes with a strong oxidizing agent, such as acidified aqueous potassium permanganate solution. In some cases, an alkyl group can be oxidized directly to a carboxyl group. This process is very important industrially. 

In general, the methods for protection and deprotection of carboxylic acids and esters are not as convenient as for alcohols, aldehydes, and ketones. It is therefore common to carry potential carboxylic acids through synthetic schemes in the form of protected primary alcohols or aldehydes. The carboxylic acid can then be formed at a late stage in the synthesis by an appropriate oxidation. This strategy allows one to utilize the wider variety of alcohol and aldehyde protective groups indirectly for carboxylic acid protection. 

Ros Barcelo, A. Pomar, F. Oxidation of cinnamyl alcohols and aldehydes by a basic peroxidase from lignifying Zinnia elegans hypocotyls. Phytochemistry 2001, 57, 1105-1113. 

Co-Oxidation of Aldehydes with Hydrocarbons, Alcohols, and Aldehydes... 

Alcohols retard the oxidation of aldehydes. The parameters of aldehyde co-oxidation with cycloolefins, alcohols, and aldehydes are collected in Table 8.6. 

The oxidation of />-toluenesulfonic acid to the corresponding alcohol and aldehyde was achieved using the Shilov system and when employing oxidants other than Pt(iv), including peroxydisulfate or phosphomolybdic acid, only moderate turnovers were observed (Equation (18)).28... 

M. Besson, and P. Gallezot, Selective oxidation of alcohols and aldehydes on metal catalysts, Catal. Today 57(1-2), 127-141 (2000). 

It is a useful oxidant for hydrocarbons, alkenes, alcohols and aldehydes. Permanganate reacts with carbon-carbon double bonds to form a cyclic manganate(V) diester. The nature of the products is determined by subsequent rapid processes. 

More recently, using the cyclometallated iridium C,(7-benzoate derived from allyl acetate, 4-methoxy-3-nitrobenzoic acid and BIPHEP, catalytic carbonyl crotylation employing 1,3-butadiene from the aldehyde, or alcohol oxidation was achieved under transfer hydrogenation conditions [274]. Carbonyl addition occurs with roughly equal facility from the alcohol or aldehyde oxidation level. However, products are obtained as diastereomeric mixtures. Stereoselective variants of these processes are under development. It should be noted that under the conditions of ruthenium-catalyzed transfer hydrogenation, conjugated dienes, including butadiene, couple to alcohols or aldehydes to provide either products of carbonyl crotylation or p,y-enones (Scheme 16) [275, 276]. 

Scheme 26 Enantioselective carbonyl (trimethytsityt)attytation and (hydroxymethyl)allylation from the alcohol or aldehyde oxidation level via iridium-catatyzed C-C bond-forming transfer hydrogenation...

Primary alcohols 121 undergo an efficient oxidative dimerization by [IrCl(coe)2]2 under air, without any solvent, to form esters 122 in fair to good yields (Equation 10.30) [54]. The reaction is initiated by the in situ generation of an Ir-hydride complex via hydrogen transfer from alcohols to afford aldehydes, followed by the dehydrogenation of hemiacetals derived from alcohols and aldehydes by action of the Ir-complex to afford esters. 

The 14c<-demethylation of dihydrolanosterol proceeds in three main stages with the two intermediates - the alcohol/ 5o -lanost-8-ene- 3p, 32-diol/ and the aldehyde/ 3p-hydroxy-5iX -lanost-8-en-32-al/ being tightly protein bound. The cytochrome P-450 is the component of the enzyme system required to initiate oxidation of the 14oC"itiethyl group/ but not of that responsible for the subsequent oxidation steps required for its elimination as formic acid (4). This initial oxidation also seems to be directly inhibited by the alcohol and aldehyde metabolities. 

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