Oxidation of alcohols to carbonyl compounds

Organobismuth(V) compounds are potential oxidants because of their inherent oxidizing ability, which derives from the facile Bi(V)/Bi(III) redox process [72], This characteristic property of bismuth has been utilized for alcohol oxidation 

14a Oxidation of Monoalcohols So far, we have generated two new and very general alcohol syntheses, the reaction of aldehydes and ketones with organometallic reagents, and the reduction of carbonyl compounds by metal hydrides. A complement to the reduction reaction is the oxidation of alcohols to 

FIGURE 16.65 Alcohols can be oxidized to carbonyl compounds. This reaction is the reverse of what you have just learned— the reduction of carbonyl compounds to alcohols through reactions with metal hydride reagents. 

FIGURE 16.66 Tertiary alcohols cannot be easily oxidized, but secondary and primary alcohols can be. It is logical to infer that in order for the oxidation reaction to succeed there must be a carbon—hydrogen bond available on the alcohol carbon. 

R2C=0 react in similar ways. For example, an alcohol oxygen is a nucleophile and can attack the chromium-oxygen bond to give, ultimately, a chromate ester intermediate (Fig. 16.67). This reaction of a Cr=0 with an alcohol is analogous to the formation of a hemiacetal from the reaction of a C O with an alcohol. 

FIGURE 16.67 Nucleophilic alcohols can add to Cr=0 bonds just as they do to C=0 bonds. This reaction is the first step in the oxidation process, and in this case gives a chromate ester intermediate. 

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Many biological processes involve oxidation of alcohols to carbonyl compounds or the reverse process reduction of carbonyl compounds to alcohols Ethanol for example is metabolized m the liver to acetaldehyde Such processes are catalyzed by enzymes the enzyme that catalyzes the oxidation of ethanol is called alcohol dehydrogenase... 

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. 

Kim, S.S. St Rajagopal, G. (2004) Efficient Aerobic Oxidation of Alcohols to Carbonyl Compounds with NHPI/CAN Catalytic System. Synthetic Communications, 33, 2237-2243. 

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. 

NR = nonreactive toward hydrocarbons PO = oxidation of phosphines to phosphine oxides MF — peroxometallacyclic adduct formation with cyanoalkenes NSE — nonstereoselective epoxidation SE=stereoselective epoxidation AE = asymmetric epoxidation HA- hydroxylation of alkanes HB=hydroxylation of arenes OA = oxidation of alcohols to carbonyl compounds K = ketonization of Lermina 1 alkenes SO oxidation of S02 to coordinated S04 MO = metallaozonide formation with carbonyl compounds I = oxidation of isocyanides to isocyanates. 

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... 

J. (2001) Palladium-catalyzed oxidation of alcohols to carbonyl compounds with 1,2-dichloroefhane as the primary oxidant a theoretical study. /. Chem. Soc., Perkin Trans., 2, 1998. 

Mannam S, Alamsetti SK, Sekar G (2007) Aerobic, chemoselective oxidation of alcohols to carbonyl compounds catalyzed by a DABCO-copper complex under mild conditions. Adv Synth Catal 349(14-15) 2253-2258... 

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