Oxidation of alcohols to aldehydes and ketones

Recently, procedures for oxidation of alcohols to aldehydes and ketones have been developed that obviate the toxicity associated with the use of chromium reagents. Because of the greater stability of ketones to most oxidizing conditions, the conversion of secondary alcohols to ketones can be accomplished with a wide variety of reagents and conditions (Table 4.1). 

The E2-like process depicted for the general oxidation mechanism in Table 4.1 is supported by the observation that deuterium substitution of the a-H in isopropanol slows the rate of chromic acid oxidation by sevenfold. Deuterium replacement at the methyl positions does not diminish the oxidation rate. Since C-D bonds are broken more slowly than C-H bonds, these results suggest that the a-H is removed in a slow step. 

Introduction. The controlled oxidation of primary and secondary alcohols yields compounds which have less hydrogen on the carbon atom to which the hydroxyl group is attached. The oxidation products of primary alcohols are represented by the general formula RCHO and are called aldehydes, the products from secondary alcohols have the general formula RjCO and are called ketones. Both compounds have the carbonyl (CO) group as a functional group. 

Thus it is easy to calculate that a third of a mole of dichromate is required for every mole of alcohol. Atmospheric oxygen may be used as the oxidizing agent. When a mixture of alcohol vapor and air is passed over hot copper, the following reactions occur  

In the laboratory (for tests), the process can be demonstrated by heating a copper spiral and plunging it into a dilute aqueous solution of methyl alcohol. The film of copper oxide acts as the oxidizing agent the process is then repeated until all of the alcohol is oxidized. 

Place in the flask 10 g of the alcohol to be oxidized and 20 ml of water. Prepare the oxidizing solution separately by dissolving 20 g of sodium dichromate in 28 ml of water and then adding slowly 16 ml of concentrated sulfuric acid. Cool the mixture to about 30°, then pour one half into an 8-inch test tube and fit the separatory 

85-95°. The final fraction which boils at 76-84° is collected as butanone. Pure butanone boils at 79.6°. The yield is 5-7 g. 

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Section 15 11 Oxidation of alcohols to aldehydes and ketones is a common biological reaction Most require a coenzyme such as the oxidized form of nicotin amide adenine dmucleotide (NAD" )... 

Alcohol dehydrogenase (Section 15.11) Enzyme in the liver that catalyzes the oxidation of alcohols to aldehydes and ketones. 

The complex Pd-(-)-sparteine was also used as catalyst in an important reaction. Two groups have simultaneously and independently reported a closely related aerobic oxidative kinetic resolution of secondary alcohols. The oxidation of secondary alcohols is one of the most common and well-studied reactions in chemistry. Although excellent catalytic enantioselective methods exist for a variety of oxidation processes, such as epoxidation, dihydroxy-lation, and aziridination, there are relatively few catalytic enantioselective examples of alcohol oxidation. The two research teams were interested in the metal-catalyzed aerobic oxidation of alcohols to aldehydes and ketones and became involved in extending the scopes of these oxidations to asymmetric catalysis. 

Some successful attempts to immobilize catalysts for the oxidation of alcohols to carbonyl compounds involve the attachment of TEMPO-derivatives to a solid phase. Bolm et al. were the first to immobilize l-hydroxy-2,2,6,6-tetramethylpiperi-dine to modified silica gel (SG-TMP-OH) (11) and applied in the oxidation of multifunctional alcohols [68]. Other groups further investigated the use of polymer-supported TEMPO [69]. This system allowed the oxidation of alcohols to aldehydes and ketones, respectively, using bleach to regenerate the immobilized ni-troxyl radical (Scheme 4.6). 

Various solid-supported perruthenate reagents have been designed for the oxidation of alcohols.Solid-supported NMO has also been used. A number of perruthenate systems employing O2 as the terminal oxidant have also been reported. The use of ionic liquids based upon substituted imidazolium cations as alternative solvent media for the selective oxidation of alcohols to aldehydes and ketones has also been investigated. ... 

The oxidation of alcohols to aldehydes and ketones using catalytic amounts of TEMPO and controlled potential electrolysis has been reported, including the observation of a special selectivity for primary alcohols in the presence of secondary alcohols (equation 20) °. The oxidation of secondary alcohol is much slower than that of primary alcohols. This method is especially effective for oxidation of the primary alcohol group in carbohydrates (equations 21 and 22) . ... 

A characteristic of catalysis processes is that a variety of compounds may catalyse a particular reaction, but only one or two of these catalysts show enough selectivity, activity and stability to warrant use in an industrial process. Selectivity is the ability of a catalyst to increase the relative rate of formation of a desired product when two or more competing reactions may occur. For modification of the direction of a reaction, mixed catalysts consisting of two compounds both with moderate to good catalytic activity have been developed. For example, the vapour phase oxidation of alcohols to aldehydes and ketones involves a mixed a- Fe203/ M0O3 catalyst rather than a single oxide. 

General Procedure for Oxidation of Alcohols to Aldehydes and Ketones by Collins Oxidation... 

The following experimental tips help to achieve best yields in oxidations of alcohols to aldehydes and ketones with PDC.127a... 

During some couplings of nucleosides, promoted by dicyclohexylcarbodii-mide (DCC), Pfitzner and Moffatt.13 decided to try dimethyl sulfoxide (DMSO) as solvent. Instead of obtaining the expected couplings, they observed oxidation of alcohols to aldehydes and ketones. These oxidations were very remarkable, because at that time, on the nucleosides tested, no oxidants were known to be able to deliver efficiently the observed aldehydes and ketones. Furthermore, contrary to many other oxidants, no over-... 

This book is dedicated to the thousands of scientists cited in the references that constructed our present knowledge on the oxidation of alcohols to aldehydes and ketones. Thanks to their collective effort, the preparation of medicines, pesticides, colorants and plenty of chemicals that make life more enjoyable, is greatly facilitated. 

The Anelli oxidation of alcohols to aldehydes and ketones has been accomplished using polymer-supported nitroxyl radical catalysts. The practicality of removing polymer-supported reagents by filtration to simplify product purification is highlighted by these examples. Bolm and coworkers11 demonstrated that a silica-supported nitroxyl catalyst is easily filtrated after use from the reaction solution, recovered and recycled, and the residual inorganic salts present in the reaction mixture are separated from the organic product by aqueous extraction (Table II, entry 7). 

The oxidation of alcohols to aldehydes and ketones is one of the most common and well-studied reactions in organic chemistry [1], Many of these processes require organic or metal oxidants. It is much more desirable to find systems that utilize oxygen and a catalyst to perform alcohol oxidation, because of the environmental and economic benefits. A number of important advances have been made in this area, as described in the preceding section (IV.1.1.6). Recently, several groups have developed enantioselective aerobic alcohol oxidations, enabling kinetic resolution of secondary alcohols [2]. 

Metal-catalyzed oxidation of alcohols to aldehydes and ketones is a subject that has received significant recent attention [21,56,57]. One such method that utilizes NHC ligands is an Oppenauer-type oxidation with an Ir or Ru catalyst [58-62]. These alcohol oxidation reactions consist of an equilibrium process involving hydrogen transfer from the alcohol substrate to a ketone, such as acetone (Eq. 5), or an alkene. Because these reactions avoid the use of a strong oxidant, the potential oxidative instability of NHC ligands is less problematic. Consequently, these reactions represent an important target for future research into the utility of NHCs. 

Palladium-catalyzed aerobic oxidation of alcohols to aldehydes and ketones have been studied extensively in recent years, and a number of effective catalysts have been developed (Chart 2). This work has been the subject of several recent reviews [21,36-38,56,64-67] and will not be summarized in depth... 

Selective oxidation of alcohols to aldehydes and ketones in high yields continues to receive attention. Geraniol (8), as the triethyltin alkoxide, is oxidized with bromine and triethyltin methoxide no double-bond isomerization is reported,43 in contrast to... 

CrOs-pyridine complex The oxidation of alcohols to aldehydes and ketones with CrOs in the presence of pyridine solvent is known as the Sarett oxidation. Sarett used the CrOs-pyridine complex in the synthesis of steroids. Although primary alcohols give poor yield, benzylic, allylic and secondary alcohols give good yields with Sarett reagent. 

A very mild oxidation procedure that tolerates a variety of other functional groups is the oxidation of alcohols to aldehydes and ketones by the dimethyl sulfoxide (DMSO). A DMSO solution of the alcohol is treated with one of the several electrophilic dehydrating reagents. The alcohol is oxidized to the aldehyde or ketone and DMSO is reduced to dimethyl sulfide (DMS), which is a volatile liquid (b.p. 37°C). Since pure DMSO freezes at 18°C and an oxidation reaction is carried out at —50°C or lower, a co-solvent such as methylene chloride or THF (tetrahydrofuran) is needed. 

Chromium(VI) oxide in various solvent systems provides an excellent oxidizing agent for alcohols, since it rapidly forms chromate esters which are intermediates in the oxidation of alcohols to aldehydes and ketones. The oxidation of [2- H]propan-2-ol showed a significant isotope effect when compared to propan-2-ol. Hence the abstraction of a proton by a base in the fragmentation of these esters is the rate-determining step in the reaction (Scheme 2.19). 

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