Alcohol oxidation is a collection ofoxidation reactions inorganic chemistry that convertalcohols toaldehydes,ketones,carboxylic acids, andesters. The reaction mainly applies to primary and secondary alcohols. Secondary alcohols form ketones, while primary alcohols form aldehydes or carboxylic acids.[1]
A variety of oxidants can be used.
Almost all industrial scale oxidations use oxygen or air as the oxidant.[2]
Through a variety of mechanisms, the removal of a hydride equivalent converts a primary or secondary alcohol to an aldehyde or ketone, respectively. The oxidation of primary alcohols to carboxylic acids normally proceeds via the corresponding aldehyde, which is transformed via analdehyde hydrate (gem-diol, R-CH(OH)2) by reaction with water. Thus, the oxidation of a primary alcohol at the aldehyde level without further oxidation to the carboxylic acid is possible by performing the reaction in absence of water, so that no aldehyde hydrate can be formed.
The largest operations involve the oxidation ofmethanol andethanol toformaldehyde andacetaldehyde, which are produced on million ton scale annually. Both processes use O2 as the oxidant. Methanol oxidation employs a molybdenum oxide-based catalyst. Other large scale aldehydes and ketones are produced byautoxidation of hydrocarbons:benzaldehyde fromtoluene,acrolein frompropylene,acetone fromcumene,cyclohexanone fromcyclohexanol.[2]
In teaching laboratories and small scale operations, many reagents have been developed for the oxidation of secondary alcohols to ketones and primary alcohols to aldehydes.Allylic andbenzylic alcohols are especially prone to oxidation. Aldehydes are susceptible to over oxidation to carboxylic acids.
Chromium(VI) reagents are commonly used for these oxidations.One family of Cr(VI) reagents employs the complex CrO3(pyridine)2.[3]
A second family of Cr(VI) reagents aresalts, featuring thepyridinium cation (C5H5NH+).
These salts are less reactive, more easily handled, and more selective than Collins reagent in oxidations of alcohols.
The above reagents represent improvements over the olderJones reagent, a solution ofchromium trioxide in aqueoussulfuric acid.
TheDess–Martin periodinane is a mild oxidant for the conversion of alcohols to aldehydes or ketones.[5] The reaction is performed under standard conditions, at room temperature, most often indichloromethane. The reaction takes between half an hour and two hours to complete. The product is then separated from the spent periodinane.[6] Many iodosyl-based oxidants have been developed, e.g.IBX.
Swern oxidation usesoxalyl chloride,dimethylsulfoxide, and an organic base, such astriethylamine.
The by-products aredimethyl sulfide (Me2S),carbon monoxide (CO),carbon dioxide (CO2) and – when triethylamine is used as base – triethylammonium chloride (C6H15NHCl).
The relatedN-tert-Butylbenzenesulfinimidoyl chloride combines both the sulfur(IV), the base, and the activating Lewis acid in one molecule.
This seldom-used method interconverts alcohols and carbonyls.
Ley oxidation usesNMO as the stoichiometric oxidant withtetrapropylammonium perruthenate as a catalyst.
Fétizon oxidation, also a seldom-used method, usessilver carbonatesupported on Celite. This reagent operates through single electron oxidation by the silver cations.
Another method is theoxoammonium-catalyzed oxidation. TEMPO exhibits a strong, pH-dependent selectivity for either primary or secondary alcohols; but the effect is primarily steric and other N-oxides behave differently.
Additionally,sodium hypochlorite (or household bleach) in acetone has been reported for efficient conversion of secondary alcohols in the presence of primary alcohols (Stevens oxidation).[7]
Soluble transition metal complexes catalyze the oxidation of alcohols by presence of dioxygen or another terminal oxidant.[8]
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The largest scale oxidation of 1,2-diols givesglyoxal from ethylene glycol. The conversion uses air or sometimesnitric acid.[2]
In the laboratory,vicinal diols suffer oxidative breakage at a carbon-carbon bond with some oxidants such assodium periodate (NaIO4),(diacetoxyiodo)benzene (PhI(OAc)2)[9] orlead tetraacetate (Pb(OAc)4), resulting in generation of twocarbonyl groups. The reaction is also known asglycol cleavage.
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The oxidation of primary alcohols to carboxylic acids can be carried out using a variety of reagents, but O2/air and nitric acid dominate as the oxidants on a commercial scale. Large scale oxidations of this type are used for the conversion of cyclohexanol alone or as a mixture with cyclohexanone toadipic acid. Similarly cyclododecanol is converted to the 12-carbon dicarboxylic acid. 3,5,5-Trimethylcyclohexanol is similarly oxidized to trimethyladipic acid.[2]
Many specialty reagents have been developed for laboratory scale oxidations of alcohols to carboxylic acids.
Potassium permanganate (KMnO4) oxidizes primary alcohols to carboxylic acids very efficiently. This reaction, which was first described in detail by Fournier,[10][11] is typically carried out by adding KMnO4 to a solution or suspension of the alcohol in an alkaline aqueous solution. For the reaction to proceed efficiently, the alcohol must be at least partially dissolved in the aqueous solution. This can be facilitated by the addition of an organic co-solvent such asdioxane,pyridine,acetone ort-BuOH. KMnO4 reacts with manyfunctional groups, such as secondary alcohols, 1,2-diols, aldehydes, alkenes, oximes, sulfides and thiols, and carbon-carbon double bonds. Thus, selectivity is an issue.
The so-calledJones reagent, prepared fromchromium trioxide (CrO3) and aqueoussulfuric acid, oxidizes alcohols to a carboxylic acid. The protocol frequently affords substantial amounts ofesters.[13] Problems are the toxicity and environmental unfriendliness of the reagent. Catalytic variant, involving treatment with excess ofperiodic acid (H5IO6) have been described.[14]
As a lot of the aforementioned conditions for the oxidations of primary alcohols to acids are harsh and not compatible with common protection groups, organic chemists often use a two-step procedure for the oxidation to acids. The alcohol is oxidized to analdehyde using one of the many procedures above. This sequence is often used in natural product synthesis as in their synthesis of platencin.[16]
Ruthenium tetroxide is an aggressive, seldom-used agent that allows mild reaction conditions.
Heyns oxidation.[17]
The use of chlorites as terminal oxidants in conjunction with both hypochlorites andTEMPO gives carboxylic acids without chlorination side products.[18] The reaction is usually carried out in two steps in the same pot:partial oxidation is effected with TEMPO and hypochlorite, then chlorite is added to complete the oxidation. Only primary alcohol oxidation is observed. In conjunction with Sharpless dihydroxylation, this method can be used to generate enantiopure α-hydroxy acids.[19]
ThePinnick oxidation usessodium chlorite.[20]
