Oxidation to Carbonyl Compounds

Oxidation with Palladium in the Homogeneous Phase. The most thoroughly studied reaction concerning the transformation of alkenes to carbonyl compounds is their oxidation catalyzed by palladium in homogeneous aqueous media.243 244 494-503 As a rule, ethylene is oxidized to acetaldehyde, and terminal alkenes are converted to methyl ketones.504 505 

Although the oxidation of ethylene to acetaldehyde was known for a number of years,506 its utility depended on the catalytic regeneration of Pd(0) in situ with cop-per(II) chloride discovered by Smidt and coworkers.507 508 Air oxidation of Cu(I) to Cu(n) makes a complete catalytic cycle. This coupled three-step transformation is known as the Wacker process [Eqs. (9.97)-(9.99)]. The overall reaction [Eq. (9.100)] is the indirect oxidation with oxygen of alkenes to carbonyl compounds  

This step, yielding a cisoid P-hydroxyethylpalladium intermediate (71), is preceded by a trans-cis isomerization (69 to 70).498 A series of hydride shifts (66 to 67 and 67 to 68) eventually leads to the product carbonyl compound. 

An important drawback of the original Wacker process is the highly corrosive nature of the aqueous acidic PdCl2—CuCl2 system. Attempts were made to apply electrochemical reoxidation of palladium,513,514 and to use other oxidants,495 such as Fe(III) salts, Mn02, quinones,514-516 peroxides,517,518 and more recently, heteropoly acids.516,519 522 

A multistep catalytic system consisting of Pd(OAc)2, hydroquinone, and an oxygen-activating complex [iron phthalocyanine, Fe(Pc)] in aqueous DMF in the 

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Perhaps the most important reaction of alcohols is their oxidation to carbonyl compounds. Primary alcohols yield either aldehydes or carboxylic acids, secondary alcohols yield ketones, but tertiary alcohols are not normally oxidized. Pyridinium chlorochromate (PCC) in dichloromethane is often used for oxidizing primary alcohols to aldehydes and secondary alcohols to ketones. A solution of Cr03 in aqueous acid is frequently used for oxidizing primary alcohols to carboxylic acids and secondary alcohols to ketones. 

Manganese dioxide (Mn02) supported on silica provides an expeditious and high-yield route to carbonyl compounds. Benzyl alcohols are selectively oxidized to carbonyl compounds by use of 35 % Mn02 doped silica under MW irradiation conditions (Scheme 6.28) [96]. 

Haynes, R.K., Lam, W.W.-L., and Yeung, L.-L., Stereoselective preparation of functionalized tertiary P-chiral phosphine oxides by nucleophilic addition of lithiated tert-butylphenylphosphine oxide to carbonyl compounds, Tetrahedron Lett., 37, 4729, 1996. 

Oxidation. Alcohols with at least one H on the carbinol carbon (1° and 2°) are oxidized to carbonyl compounds. 

By a suitable choice of activating reagents, primary and secondary alcohols can be selectively oxidized to carbonyl compounds in good yields at room temperatures. Typical activating reagents ate acetic anhydride, sulfur trioxide—pyridine, dicyclohexyl catbodiimide, and phosphorus pentoxide (40). 

OxidationAllylic and benzylic alcohols are oxidized to carbonyl compounds in 70-80% yield by K.2Cr207 in either DMSO or polyethylene glycol, in which the reagent is reasonably soluble. 

Oxidation of alcohols. 1 Secondary alcohols are oxidized to carbonyl compounds by Clayfen in pentane or hexane under vigorous stirring. Primary benzyl alcohols are oxidized satisfactorily, but primary aliphatic alcohols are oxidized to complex mixtures. Isolated yields are generally>80%. Nitrite esters (RONO) have been identified as intermediates. 

Ube Industries LtdinYamaguchi, Japan, and Kyoto University investigated the Swern oxidation for pharmaceutical intermediates [57,58]. In this reaction, alcohols are oxidized to carbonyl compounds using dimethyl sulfoxide. The reaction variant using dimethyl sulfoxide activated by trifluoroacetic anhydride (shown below) has found industrial application, but is limited to low-temperature operation (—50 °C or below) to avoid decomposition of an intermediate. 

Halides are extremely versatile intermediates. One of their more valuable and interesting transformations is dieir oxidation to carbonyl compounds, dius providing straightforward routes to relatively inaccessible compounds such as 1,2-diketones and heterocyclic aldehyde. As will be seen below, there are many, often complementary, syndietic methods for die oxidation of organic halides. The oxidation of halomediyl compounds has been reviewed recently. ... 

At high concentration, (Cr03) and chromic acid (H2Cr04) are the main species. As alcohol is oxidized to carbonyl compound, Cr(VI) is reduced to Cr(III). However, the detail mechanism shows that Cr(V) and Cr(IV) species are also involved in the oxidation of alcohols. The Cr(VI) species are usually HCr04 and CrOs and the Cr(IV) is usually HCr03. The balanced equation for the oxidation of alcohols with chromic acid involves both acid catalyst and water as shown below ... 

In the alcohol oxidation to carbonyl compounds several Cr(VI) reagents can be used such as CrOs in aqueous acetic acid or in other solvents along with catalytic amount of mineral acid, sodium dichromate in aqueous acetone and mineral acid or base as catalyst, sodium dichromate in acetic acid, Cr03-pyridine complex and terf-butyl chromate. 

Oxidation of alcohols. Alcohols can be oxidized to carbonyl compounds by f-butyl hydroperoxide (slight excess) and a diaryl diselenide (0.1-0.5 equiv.). Diphenyl diselenide is satisfactory, but bis(2,4,6-trimethylphenyl) diselenide is generally more satisfactory. The method is particularly efficient for benzylic and primary allylic alcohols (12 hours, 87-100% yield) oxidation of saturated alcohols, primary and secondary, requires 4-17 hours, but still proceeds in excellent yield. 

Oxidation i/ thiocarbonyl compoands. Thiocarbonyl compounds are oxidized to carbonyl compounds by DMSO in the presence of acid catalysts (sulfuric acid. 

Benzoyl peroxide (dibenzoyl peroxide), (CjHjCOO>2 (mp 104-106 °C dec), and /r-nitrobenzoyl peroxide (p-02NCgH4COO)2 (mp 156 °C dec), which is synthesized from p-nitrobenzoyl chloride and sodium peroxide [229], are rarely used as oxidants, and if so, they do not offer appreciable advantages over other organic oxidation agents. The anti addition of benzoyl groups to double bonds and the benzoxylation of aromatic rings are achieved in the presence of iodine [230], and alcohols are oxidized to carbonyl compounds in the presence of nickel dibromide [231],... 

Acetoxylations (oxyacylations) have to be seen in context with olefin oxidation to carbonyl compounds (Wacker process, Section 2.4.1). With the lowest olefin, ethylene, acetaldehyde is formed. In water-free acetic acid no reaction takes place. Only in the presence of alkali acetates - the acetate ion shows higher nu-cleophilicity than acetic acid - ethylene reacts with palladium salts (eq. (1)) to give vinyl acetate, the expected product, as first reported by Moiseev et al. [1]. Stem and Spector [2] independently used [HP04] as base in a mixture of isooctane and acetic acid. This reaction could be exploited for a commercial process to produce vinyl acetate and closed the last gap replacing acetylene by the cheaper ethylene, a petrochemical feed material, for the production of large-tonnage chemical intermediates. 

Allylic and benzylic alcohols are oxidized to carbonyl compounds with the Pd(0Ac),-02/DMS0 system. " The behavior of benzylic bromides toward (PhjPjCoCI differs in the presence or absence of oxygen under oxidative conditions aldehydes are formed, otherwise C-C bond coupling occurs. ... 

Oxidations. Secondary and benzylic alcohols are oxidized to carbonyl compounds by NaBrOj-NH Cl in aqueous MeCN. 1,2-Diols are converted to a-ketols, but the oxidation is sensitive to solvents. Thus, addition of dichloromethane changes the product profile, affording a-diketones. 

Selective oxidation of alcohols with ion-supported hypervalent iodine(III) reagent was investigated by Zhang et al. [19]. This reaction was carried out in [emim][BF ] using l-(4-diacetoxyiodobenzyl)-3-methylimidazolium tetrafluorob-orate [dibmim][BF ] as an oxidant in the presence of a low concentration of bromide ions under mild conditions. A variety of primary and secondary alcohols were oxidized to carbonyl compounds in moderate to excellent yields at room temperature, but secondary alcohols were oxidized over longer reaction times (Scheme 14.19). 

Oxidation. Oxidation of alkyl halides by DMSO requires high temperatures (100-150°), and yields are relatively low except for primary iodides (1, 303). Epstein and Ollinger11 find that halides can be oxidized to carbonyl compounds by DMSO at room temperature (4-48 hours) in the presence of silver perchlorate as assisting agent. Chlorides are relatively unreactive, but bromides and iodides are oxidized relatively easily. Yields are higher with primary halides than with secondary halides. Cyclohexyl halides are oxidized to only a slight extent to cyclohexanone, the main product being cyclohexene, formed by elimination. 

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