Oxidation of Alcohols and Carbonyl Compounds

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The processes of life also depend on oxidation of organic substrates, whereby metabolic energy is derived from the overall oxidation of carbohydrates, fats, and proteins to carbon dioxide and water, among other products, as illustrated in Equation 16.5. Potentially poisonous substances are commonly detoxified by biological oxidation to more benign substances. Thus, nicotine, which is toxic to humans if present in sufficiently high concentration, is oxidized in the liver to cotinine (Eq. 16.6), a substance of low toxicity. 

Select the carbon atom whose oxidation number is to be determined. 

Assign oxidation numbers to the atoms attached to this carbon atom using the following values  

Simply put, with respect to the atoms bound to the carbon atom, those that are more electronegative are assigned a value of -1, whereas those that are less electronegative are given a value of +1. 

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Dimethyl sulfoxide reacts with trifluoroacetic anhydride at low tempera ture to give a complex that is an efficient reagent for the oxidation of alcohols to carbonyl compounds [40 41] This reagent can be used to oxidize primary and secondary aliphatic alcohols, cycloalkyl alcohols, and allylic, homoallylic, ben-zylic, acetylenic, and steroidal alcohols (equation 19)... 

The oxidation of alcohols to carbonyl compounds by permanganate proceeds most rapidly in basic solution and it is with this medium that the majority of kinetic studies have been performed. 

Attempts to achieve selective oxidations of hydrocarbons or other compounds when the desired site of attack is remote from an activating functional group are faced with several difficulties. With powerful transition-metal oxidants, the initial oxidation products are almost always more susceptible to oxidation than the starting material. When a hydrocarbon is oxidized, it is likely to be oxidized to a carboxylic acid, with chain cleavage by successive oxidation of alcohol and carbonyl intermediates. There are a few circumstances under which oxidations of hydrocarbons can be synthetically useful processes. One group involves catalytic industrial processes. Much effort has been expended on the development of selective catalytic oxidation processes and several have economic importance. We focus on several reactions that are used on a laboratory scale. 

A facile method for the oxidation of alcohols to carbonyl compounds has been reported by Varma et al. using montmorillonite K 10 clay-supported iron(III) nitrate (clayfen) under solvent-free conditions [100], This MW-expedited reaction presumably proceeds via the intermediacy of nitrosonium ions. Interestingly, no carboxylic acids are formed in the oxidation of primary alcohols. The simple solvent-free experimental procedure involves mixing of neat substrates with clayfen and a brief exposure of the reaction mixture to irradiation in a MW oven for 15-60 s. This rapid, ma-nipulatively simple, inexpensive and selective procedure avoids the use of excess solvents and toxic oxidants (Scheme 6.30) [100]. Solid state use of clayfen has afforded higher yields and the amounts used are half of that used by Laszlo et al. [17,19]. 

The oxidation of alcohols in a basic solution catalyzed by Cu(II) o-phenanthroline complexes has been recently studied by Sakharov and Skibida [305-309], The copper-phe-nanthroline complex is stable in a basic solution and appears to be a very efficient catalyst for the oxidation of alcohols to carbonyl compounds. The reaction rate increases with an increase in the partial pressure of dioxygen. The solvent dramatically influences the reaction rate (conditions 348 K, [MeOH] = 20%vol, [Cu—(o—phm)] = 0.01 mol L-1). 

The oxidation of alcohols to carbonyl compounds has been studied by several authors and a variety of methods have been used. Papers concerned vith such oxidations are illustrated (Scheme 3.26). Good results have been obtained using pyridinium chlor-ochromate (PCC) adsorbed onto silica gel for the selective oxidation of unsaturated substrates e.g. terpene [135] and furanyl derivatives [136]. Steroidal homoallylic alcohols can be converted to the corresponding 4-ene-3,6-diones using tetrapropylammo-nium per-ruthenate (TPAP) in catalytic amounts [137]. In this case, the oxidising agent is N-methyl morpholine N-oxide (NMO). 

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). 

Oxidation of alcohols to carbonyl compounds is an important reaction. Stoichiometric oxidants such as chromates, permanganates and MO4 (M = Ru, Os) are the commonly used reagents [19a,59,60]. However, they are going out of favour increasingly because they create heavy metal wastes . In view of this, development of environmentally friendly heterogeneous catalysts for alcohol oxidation is very important. In the use of catalytic amounts of transition metal salts or complexes as homogeneous catalysts for the oxidation of alcohols [61-64], separation of the catalyst from the reaction mixture and its subsequent recovery in active form is cumbersome. Heterogeneous catalysts for this kind of reaction are therefore necessary [65]. Clearly, encapsulation and/or immobilization of known... 

Berkessel and Sklorz screened a variety of potential co-ligands for the Mn-tmtacn/H202 catalyzed epoxidation reaction and found that ascorbic acid was the most efficient one. With this activator the authors could oxidize the terminal olefins 1-octene and methyl acrylate with full conversion and yields of 83% and 97%, respectively, employing less than 0.1% of the metal complex (Scheme 86). Furthermore, with E- and Z-l-deuterio-1-octene as substrates, it was shown that the oxygen transfer proceeded stereoselectively with almost complete retention of configuration (94 2%). Besides the epoxidation, also the oxidation of alcohols to carbonyl compounds could be catalyzed by this catalytic system (see also Section in.C). 

The dehydrogenases discussed in this section catalyze the oxidation of alcohols to carbonyl compounds. They utilize either NAD+ or NADP+ as coenzymes. The complex of the enzyme and coenzyme is termed the holoenzyme the free enzyme is called the apotnzyme. Some dehydrogenases are specific for just one of the coenzymes a few use both. The reactions are readily reversible, so that carbonyl compounds may be reduced by NADH or NADPH. The rates of reaction in either direction are conveniently measured by the appearance or disappearance of the reduced coenzyme, since it has a characteristic ultraviolet absorbance at 340 nm. The reduced coenzymes also fluoresce when they are excited at 340 nm, which provides an even more sensitive means of assay. 

The oxidative properties of chromium-oxo complexes towards organic substrates have been thoroughly investigated, and several reviews have appeared in recent years.270 276 We will only briefly consider the oxidation of alcohols to carbonyl compounds, the epoxidation of alkenes and the hydroxylation of hydrocarbons. 

Freshly prepared Mn02 is a useful reagent in organic chemistry and has been used in a large variety of oxidative transformations.311 These reactions involve the allylic oxidation of alkene to a,/3-unsaturated carbonyl compounds, the transformation of methylarenes to benzaldehyde and benzoic acid derivatives, the oxidation of secondary methylene groups to ketones, and the oxidation of alcohols to carbonyl compounds.311 The yields are generally fair to good. 

The simplest sulphoxide, dimethyl sulphoxide, is an important aprotic solvent (Section 4.1.55, p. 412). Its use as a reagent in carbon-carbon forming reactions and as a reagent for the oxidation of alcohols to carbonyl compounds (p. 608) (the Pfitzner-Moffatt and Swern oxidations) has been extensively reviewed.244 An illustrative example of carbon-carbon bond formation using dimethyl sulphoxide is noted in Expt 7.3. 

The oxidation of alcohols to carbonyl compounds is one of the most relevant transformations in organic synthesis, due to the large diversity of products that can be obtained from aldehyde and ketone precursors. 

A new catalytic system consisting of a persistent macrocyclic aminoxyl radical and the couple Mn(N03)2-Co(NC>3)2 for the aerobic oxidation of alcohols to carbonyl compounds has been developed. The rate-determining step has been identified by studying the effect of substituents on the oxidation of benzyl alcohol. The chemistry of aminoxyl, amidoxyl, and imidoxyl radicals has been discussed.265... 

The oxidation of alcohols to carbonyl compounds with the stable nitroxyl radical TEMPO (86) as catalyst is a well-known preparative method [134, 135]. Hypochlorite or peracetic acid is usually used as the final oxidizing agent and ca. 1 mol% of catalyst 86 is used. In 1996 Rychnovsky et al. reported the synthesis of the chiral, binaphthyl-derived TEMPO analog 87 [136], Results obtained by use of 0.5-1 mol% of catalyst 87 [136] are listed in Table 10.12. In these oxidation reactions 0.6-0.7 equiv. sodium hypochlorite were used as the final oxidizing agent (plus... 

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