Oxidation of alcohol

Alcohols react with carboxylic acids to give esters, a reaction that is common in both the laboratory and living organisms. In the laboratory, the reaction can be carried out in a single step if a strong acid is used as catalyst. More frequently, though, the reactivity of the carboxylic acid is enhanced by first converting it into a carboxylic acid chloride, which then reacts with the alcohol. We ll look in detail at the mechanisms of these reactions in Chapter 21. 

In living organisms, a similar process occurs, although a tliioester or acyl adenosyl phosphate is the substrate rather than a carboxylic acid chloride. 

Perhaps the most valuable reaction of alcohols is their oxidation to yield car-bony compounds—the opposite of the reduction of carbonyl compounds to yield alcohols. Primary alcohols yield aldehydes or carboxylic acids, secondary alcohols yield ketones, but tertiary alcohols don t normally react with most oxidizing agents. 

Primary alcohols are oxidized to either aldehydes or carboxylic acids, depending on the reagents chosen and the conditions used. One of the best methods for preparing an aldehyde from a primary alcohol on a small laboratory scale, as opposed to a large industrial scale, is to use pyridinium chloro-chromate (PCC, CsH NCrO Cl) in dichloromethane solvent. 

Most other oxidizing agents, such as chromium trioxide (0rO3) in aqueous acid, oxidize primary alcohols directly to carboxylic acids. An aldehyde is involved as an intermediate in this reaction but can t usually be isolated because it is further oxidized too rapidly. 

Alcohols are oxidized slowly with PdCl2 or Pd(OAc)2. The reaction is explained by formation of Pd-alkoxide 481, followed by -H elimination. More efficient methods of oxidation using palladium catalysts and O2 as an oxidant have been reported by several groups. Primary alcohols are oxidized to carboxylic acids using Pd-phenanthroline 482 as a catalyst, which can be recycled [198]. 

Primary and secondary alcohols such as benzyl alcohol (483) and 1-phenylethanol (484) are oxidized with O2 efficiently to benzaldehyde and acetophenone using Pd(OAc)2, complexed with pyridine, as a catalyst in the presence of a molecular sieve [199] or supported on hydrotalcite [200]. Also, the palladacycle of 4,5-dihydro-l,3-oxazole 485 is a good catalyst for oxidation of alcohols in DMSO under oxygen [201]. 

Oxidative rearrangement and ring expansion of strained molecules of tert-cyclo-butanols are known [206]. Recently it has been claimed that the reaction can be explained more reasonably by elimination of jS-carbon (see Chapter 3.8.2) [207]. Conversion of the vinylcyclobutanol 490 to the ring-opened product 493 by relief of the ring strain under oxidative conditions is explained by j6-carbon elimination as shown by 491 to generate 492, followed by j6-H elimination. In this ease. 

As another possibility, the reaction is explained by precoordination of PdX2 to the double bond. Then palladation occurs with concomitant rearrangement and ring expansion as shown by 507 to generate 505 and then 506. 

Treatment of the l-isopropenyl-2-(3-butenyl)cyclobutanol 508 with Pd(II) afforded the bicyclo[4.3.0]nonane 512. The reaction can be understood by domino -carbon elimination as shown by 509, followed by 5-exo and 6-exo cyclizations of 510 to give 511, and f-H elimination and isomerization afforded 512 [208], A different mechanism based on ring expansion was given before. 

Primary alcohols can be oxidized to aldehydes by reagents like pyridinium dichromate (PDC), and pyridinium chlorochromate (PCC). 

Secondary alcohols can also be oxidized. The product is a ketone. Sample reaction 21-9 

Since tertiary alcohols do not have a hydrogen atom in the carbon carrying the hydroxyl group, they carmot be easily oxidized. 

Strong oxidizing agents can oxidize alcohols to carboxylic acids. We can use potassium permanganate or chromic acid to do this conversion. 

Primary alcohol i oxidization Aldehyde I oxidization Carboxylic acid 

Oxidation of an alcohol yields a carbonyl compound. Whether the resulting carbonyl compound is an aldehyde, a ketone, or a carboxylic acid depends on the alcohol and on the oxidizing agent. 

Primary alcohols may be oxidized either to an aldehyde or to a carboxylic acid  

Vigorous oxidation leads to the formation of a carboxylic acid, but there are a number of methods that permit us to stop the oxidation at the intermediate aldehyde stage. The reagents that are most commonly used for oxidizing alcohols are based on high-oxidation-state transition metals, particularly chromium(Vl). 

Chromic acid (H2Cr04) is a good oxidizing agent and is formed when solutions containing chromate (Cr04 ) or dichromate (Cr207 ) are acidified. Sometimes it is possible to obtain aldehydes in satisfactory yield before they are further oxidized, but in most cases carboxylic acids are the major products isolated on treatment of primary alcohols with chromic acid. 

Conditions that do permit the easy isolation of aldehydes in good yield by oxidation of primary alcohols employ varions Cr(VI) species as the oxidant in anhydrous media. Two snch reagents are pyridinium chlorochromate (PCC), C5H5NH ClCrOs, and pyridinium dichromate (PDC), (CsH5NH)2 Cr207 both are used in dichloromethane. 

Oxidation of benzyl alcohol in the absence of solvent on 1% (Au-Pd)/Ti02 catalyst with pure oxygen was performed in silicon-glass micropacked bed reactors [159]. 

A pillar structure of small rectangular posts was incorporated near the outlet of the reaction channel to retain the catalyst. The reaction was studied in the temperature range of 80-120 °C and at inlet pressures up to 5 bar. Benzyl alcohol conversion and benzaldehyde selectivity at 80 and 120 °C were very close to those from conventional glass stirred reactors. The best conversion of benzyl alcohol of 95.5% with selectivity to benzaldehyde of 78% was obtained for a micropacked bed reactors with catalyst sizes of 53-63 pm and a catalyst bed length of 48 mm at 120 °C and 5 bar. The effect of catalyst particle size on the reaction was examined with two ranges of particle size 53-63 pm and 90-125 pm. Lower conversion was obtained with particle sizes of 90-125 pm, indicating the presence of internal mass transfer resistances. In situ Raman measurements were performed and could be used to obtain the benzaldehyde concentration profile along the catalyst bed. 

Photocatalytic oxidation of p-chlorophenol and toluene under gas-liquid-solid multiphase flow conditions was investigated using a photocatalytic microreaction system [160]. By loading both gaseous and liquid samples simultaneously into a microchannel with a photocatalytic titanium dioxide thin layer therein, a gas-liquid-solid multiphase annular flow was generated. The reaction yield was greatly enhanced with decreasing thickness of liquid layer because of improved efficiency of interaction and mass transfer between different phases. 

The reaction of a a,co-diol, which has a longer methylene chain than 1,4- and 1,5-diols, gives the corresponding polyesters (Eq. 3.6) [12bj. 

Asymmetric lactonization of prochiral diols has been performed vsdth chiral phosphine complex catalysts (Ru2Cl4((-)-DIOP)3 and [RuCl((S)-BINAP)(QH6)]Cl [17, 18]. Kinetic resolution of racemic secondary alcohol was also carried out with chiral ruthenium complexes 7 and 8 in the presence of a hydrogen acceptor, and optically active secondary alcohols were obtained with 99% e.e. (Eqs. 3.7 and 3.8) [19, 20]. 

A hydroxycyclopentadienyl ruthenium chloride, ( -Ph4C4COH)(CO)2RuCl-cata-lyzed oxidation of alcohols in the presence of chloroform occurs to give carbonyl compounds along with CH2CI2 and HCl [30]. 

Entry Catalyst Oxidant Condition Alcoohol Product Yield (%) Reference  

4 (n-Pr4N)(Ru04) 02 MS4A C6H5CH3 70 X OH n-CgHia 0 n-CgHia 88 35 

Similarly, secondary alcohols have been oxidised under microwave 

Also oxidation of linear and cyclic secondary alcohols and benzylic alcohols to the corresponding carbonyl compounds under microwave irradiation conditions can be achieved. 

Stereochemical consequences of SN2 reactions on derivatives of (R)-2-octano1. Substitution via the halide gives a product with the same stereochemistry as the starting alcohol substitution via the tosylate gives a product with opposite stereochemistry to the starting alcohol. 

Primary alcohols yield aldehydes or carboxylic acids, secondary alcohols yield ketones, but tertiary alcohols don t normally react with most oxidizing agents. 

The Oxidation of Alcohols, Ketones, Ethers, Esters and Acids in Solution 

Alcohols, ketones, and acids are formed as intermediates in the liquid phase oxidation of hydrocarbons [1] and are subject to further conversions. Therefore, investigation of the mechanisms of such conversions is necessary for the correct understanding of hydrocarbon oxidation. Moreover, the oxidation of alcohols and ketones is of scientific interest proper. The role of polar media and hydrogen bonding in chain oxidation is studied, particularly for alcohols and ketones. Alcohols are very convenient for the investigation of ionic oxidation reactions. The oxidation of certain alcohols is of interest for technology. For example, acetic acid and ethyl acetate may be produced by the oxidation of ethanol, and acetone and hydrogen peroxide by the oxidation of 2-propanol. 

The oxidation of alcohols to carbonyl compounds is a fundamental reaction that has synthetic and chemical importance. Using chromium-based catalysts, researchers have developed several catalysts that have impacted alcohol oxidation reactions. Recently, homogeneous catalysts have had problems with catalyst/product separation and suffer from poor catalyst recyclability. Therefore, the quest for a resolution to this problem has led researchers to scaffold salen complexes onto a silica-based material such as MCM-41. Zhou et al. used an ion-exchangeable, layered polysiloxane support to immobili.se their sulfonato-(salen)Cr(m) complex. They reacted benzyl alcohol, cyclo-hexanol and -hexanol with hydrogen peroxide as oxidant in an ionic liquid at 40 °C. Several ionic liquids were investigated [BMImX (BMIm = 1-n-butyl-3-methylimidazolium X =PF6, BF4, NOs )] and compared for each substrate. 

Several green and sustainable chemistry concepts are supported by the use of this reaction. The first is the use a chromium complex immobilised on a silica support to give a heterogeneous catalyst for easier recyclability and separation from the product mixture. Moreover, the use of ionic liquids is favourable for catalyst recyclability. The chemical nature of the catalyst possessing ionic or polar properties can fix the catalyst in the ionic liquids 

The oxidation of alcohols, in particular secondary alcohols, can be achieved using many metal nitrates in combination with a solid support. For example, copper nitrate on silica gel gives a 98% yield of ketone on 

Potassium permanganate (KMn04) oxidises unsaturated secondary alcohols at the point of unsaturation. However, KMn04 supported on bentonite clay oxidises the hydroxyl group in preference to the alkene (e.g. equation 4.26) [122]. Unsaturated primary alcohols give virtually no reaction and allylic alcohols are oxidised much more readily than non-allylic ones. 

The stereochemistry of the polar groups in a steroid determines the orientation of the molecule when it is adsorbed onto the celite surface and this allows the position of oxidation to be controlled (e.g. equation 4.28) [124, 126, 127]. Many other alcohols, diols and triols are selectively oxidised by silver carbonate on celite [128]. 

Hydrogen peroxide in conjunction with TS-1, a medium-pore titanosili-cate, oxidises a wide range of alcohols (e.g. equation 4.29) [129]. 

4A Oxidation of Primary Alcohols to Aldehydes RCHgOH-------- RCHO 

Primary alcohols can be oxidized to aldehydes and carboxylic acids  

An excellent reagent to use for converting a primary alcohol to an aldehyde is pyridinium chlorochromate (abbreviated PCC), the compound formed when CrOs is dissolved in hydrochloric acid and then treated with pyridine  

Pyridinium chlorochromate does not attack double bonds. 

One reason for the success of oxidation with pyridinium chlorochromate is that the oxidation can be carried out in a solvent such as CH2CI2, in which PCC is soluble. Aldehydes themselves are not nearly so easily oxidized as are the aldehyde hydrates, RCH(OH)2, that form (Section 16.7A) when aldehydes are dissolved in water, the usual medium for oxidation by chromium compounds  

To oxidise alcohols, acidic solutions of strong oxidising agents, such as KMn04, K2Cr207 or K2Cr04 are used. 

The degree of oxidation of alcohols depends on the number of H atoms bonded to the carbon atom bearing the — OH group. 

Primary alcohols Secondary alcohols Tertiary alcohols 

The oxidation of primary and secondary alcohols into the corresponding carbonyl compounds plays a central role in organic synthesis [1, 139, 140]. Traditional methods for performing such transformations generally involve the use of stoichiometric quantities of inorganic oxidants, notably chromium(VI) reagents [141]. However, from both an economic and environmental viewpoint, atom efficient, catalytic methods that employ clean oxidants such as 02 and H202 are more desirable. 

In aerobic oxidations of alcohols a third pathway is possible with late transition metal ions, particularly those of Group VIII elements. The key step involves dehydrogenation of the alcohol, via -hydride elimination from the metal alkoxide to form a metal hydride (see Fig. 4.57). This constitutes a commonly employed method for the synthesis of such metal hydrides. The reaction is often base-catalyzed which explains the use of bases as cocatalysts in these systems. In the catalytic cycle the hydridometal species is reoxidized by 02, possibly via insertion into the M-H bond and formation of H202. Alternatively, an al-koxymetal species can afford a proton and the reduced form of the catalyst, either directly or via the intermediacy of a hydridometal species (see Fig. 4.57). Examples of metal ions that operate via this pathway are Pd(II), Ru(III) and Rh(III). We note the close similarity of the -hydride elimination step in this pathway to the analogous step in the oxometal pathway (see Fig. 4.56). Some metals, e.g. ruthenium, can operate via both pathways and it is often difficult to distinguish between the two. 

A variety of compounds are available that oxidize alcohols. For many years, a commonly used reagent was chromic acid (H2Cr04), which is formed when sodium dichromate (Na2Cr207) is dissolved in aqueous acid. Notice that secondary alcohols are oxidized to ketones. 

Primary alcohols are initially oxidized to aldehydes by chromic acid. The reaction, however, does not stop at the aldehyde. Instead, the aldehyde is further oxidized to a carboxylic acid. These reactions are easily recognized as oxidations because the number of C—H bonds in the reactant decreases and the number of C—O bonds increases (Section 6.8). 

Pyridine chlorochromate (PCC) is a gentler oxidizing agent. It also oxidizes secondary alcohols to ketones, but it stops the reaction at the aldehyde when it oxidizes primary alcohols. PCC must be used in an anhydrous solvent such as CH2CI2 because if water is present, the aldehyde will be further oxidized to a carboxylic acid. 

Notice that, in the oxidation of both primary and a secondary alcohols, a hydrogen is removed from the carbon to which the OH is attached. The carbon bearing the OH group in a tertiary alcohol is not bonded to a hydrogen, so its OH group cannot be oxidized to a carbonyl (C=0) group. 

Because of the toxicity of chromium-based reagents, other reagents for the oxidation of alcohols have been developed. One of the more common is hypochlorous acid (HOCl). HOCl is unstable, so it is generat in situ (in the reaction mixture) by an acid-base reaction between H and OCl (using CH3COOH and NaOCl). Secondary alcohols are oxidized to ketones and primary alcohols are oxidized to aldehydes. Also see the Swem oxidation (Problem 70). 

A few of the more common laboratory processes for other alcohols are provided in Table 8.5. 

Benzene forms a ternary azeotrope with water and ethanol (18.5% ethanol, 7.4 % water, and 74.1% benzene), which distills first. 

A balanced equation for the oxidation of some unspecified alcohol to some unspecified carbonyl compound (aldehyde or ketone) is provided in Equation 8.8. 

TABLE 8.5. A Few of the Many Different Oxidation Reactions That Have Been Carried Ont on Alcohols 

1-Triacetoxy-l, 1-dihydro-l,2-benziodoxol-3(l//)-one (Dess-Martin triacetoxyperiodinane) 

Oxidative cleavage is commonly carried out with O3, followed by cleavage of the intermediate ozonide with H2O. 

Problom 12.23 Draw the products formed when each alkyne is treated with O3 followed by HpO. 

Problem 12.24 what alkyne (or diyne) yields each set of oxidative cleavage products  

Alcohols are oxidized to a variety of carbonyl compounds, depending on the type of alcohol and reagent. Oxidation occurs by replacing the C-H bonds on the carbon bearing the OH group by C-O bonds. 

2° Alcohols are oxidized to ketones by replacing the one C-H bond by a C-O bond. [O] 

Problem 12.25 Wh alkyne (or diyn c eac setpf oxidative cleavage products  

Oxidative Methods.—Oxidation of Alcohols. Benzoyl peroxide catalysed by nickel(ii) bromide gives high yields of aldehydes and ketones from the corresponding alcohols. Similar yields are obtained with t-butyl hydroperoxide catalysed by diaryl diselenides, a method particularly recommended for benzylic or allylic alcohols. Ketones are obtained from secondary alcohols using hydrogen peroxide catalysed by molybdenum or tungsten peroxo-complexes/ and nickel peroxide has been employed to prepare a-allenic aldehydes and ketones from allenic alcohols.  

After examining a range of quinquevalent bismuth reagents Barton et al. have recommended triphenylbismuth carbonate, which oxidizes alcohols in the presence of thiols, indoles, and pyrroles.  

Secondary alcohols have been oxidized to ketones with bromobenzene catalysed by a palladium(O) complex,  

Further investigations of oxidations by dimethyl sulphoxide activated by oxalyl chloride have shown the system to be of general use, although allenic and acetylenic alcohols are not oxidized. The same reagent activated by dicyclo-hexylcarbodi-imide has been reported to yield ketones from alcohols in the presence of dithianes/° 

Several references have appeared on the use of solid-phase oxidants. Solid potassium permanganate-copper sulphate mixtures oxidize secondary alcohols to ketones in high yield, and pyridinium chromate or chromic acid on silica gel are described as convenient off-the-shelf reagents for oxidation of both primary and secondary alcohols. Anhydrous chromium trioxide-celite effects similar transformations only when ether is present as co-solvent. An excellent review, with over 400 references, on supported oxidants covers the use of silver carbonate-celite, chromium trioxide-pyridine-celite, ozone-silica, chromyl chloride-silica, chromium trioxide-graphite, manganese dioxide-carbon, and potassium permanganate-molecular sieve. 

Oxidation by these reagents of the various primary and secondary alcohols we have been making in this chapter takes us to a higher oxidation level. Oxidation of primary alcohols gives aldehydes and then carboxylic acids, while oxidation of secondary alcohols gives ketones. Note that you can t oxidize tertiary alcohols (without breaking a C—C bond). 

Here Cr(VI) can remove electrons to make Cr(III). It does so by a cyclic mechanism on a Cr(VI) ester. One hydrogen atom is removed (from the OH group) to make the ester and the second is removed (from carbon) in the cyclic mechanism. Notice how the arrows stop on the Cr atom and start again on the Cr=0 bond, so two electrons are added to the chromium. This actually makes Cr(lV), an unstable oxidation state, but this gives green Cr(III) by further reactions. 

Two examples of the use of PCC in these oxidations come from Vogel. Hexanol is oxidized to hexanal in dichloromethane solution and commercial carveol (an impure natural product) to pure carvone with PCC supported on alumina in hexane solution. In both cases the pure aldehyde or ketone was isolated by distillation. 

But a word of warning stronger oxidizing agents like calcium hypochlorite or sodium hypochlorite (bleach) may oxidize primary alcohols all the way to carboxylic acids, especially in water. This is the case with p-chloro benzyl alcohol and the solid acid is easily isolated by the type of acid/base extraction we met in the previous chapter. 

CHAPTER 9 USING ORGANOMETALLIC REAGENTS TO MAKE C-C BONDS 

Secondary alcohols are oxidized easily and in high yield to give ketones. For large-scale oxidations, an inexpensive reagent such as Na2Cr207 in aqueous acetic acid is used. 

In a similar manner, toluene-p-sulfonate derivative of alcohols on nucleophilic displacement with trimethylamine N-oxide followed by treatment with a base gives the carbonyl compound and trimethylamine. 

The direct electrochemical oxidation of aliphatic alcohols occurs at potentials which are much more positive than 2.0 V w. SCE. Therefore, the indirect electrolysis plays a very important role in this case. Using KI or NaBr as redox catalysts those oxidations can be performed already at 0.6 V vs. SCE. Primary alcohols are transformed to esters while secondary alcohols yield ketones In the case of KI, the iodo cation is supposed to be the active species. Using the polymer bound mediator poly-4-vinyl-pyridine hydrobromide, it is possible to oxidize secondary hydroxyl groups selectively in the presence of primary ones (Table 4, No. 40) The double mediator system RuOJCU, already mentioned above (Eq. (29)), can also be used effectively Another double mediator system 

Ley et al. performed oxidations of activated (benzyhc, allylic) alcohols by employing polymer-attached perruthenate catalysts and oxygen as oxidant. Triethylammo- 

In this context, it was shown that polymer-supported triphenylphosphine as a ligand for metal-based oxidation is an alternative catalytic system [72]. 

What alcohols would give the following products on oxidation (a) 0 (b) CH3 (c) 

According to the scale of oxidation levels established for carbon (see Table 11-1), primary alcohols (RCH2OH) are at a lower oxidation level than either aldehydes (RCHO) or. carboxylic acids (RC02H). With suitable oxidizing agents, primary alcohols in fact can be oxidized first to aldehydes and then to carboxylic acids. 

Unlike the reactions discussed previously in this chapter, oxidation of alcohols involves the alkyl portion of the molecule, or more specifically, the C-H bonds of the hydroxyl-bearing carbon (the a carbon). Secondary alcohols, which have only one such C-H bond, are oxidized to ketones, whereas tertiary alcohols, which have no C-H bonds to the hydroxylic carbon, are oxidized only with accompanying degradation into smaller fragments by cleavage of carbon-carbon bonds. 

Conversion of ethanol to ethanal is carried out on a commercial scale by passing gaseous ethanol over a copper catalyst at 300°  

At room temperature this reaction is endothermic with an equilibrium constant of about 10 22. At 300° conversions of 20%-50% per pass can be realized and, by recycling the unreacted alcohol, the yield can be greater than 90%. 

Another commercial process uses a silver catalyst and oxygen to combine with the hydrogen, which makes the net reaction substantially exothermic  

Secondary alcohols are oxidized to form ketones, which are not easily oxidized because there is no hydrogen atom on the carbonyl carbon atom of the ketone. Tertiary alcohols are not oxidized because the carbon atom bearing the hydroxyl group does not have a hydrogen atom. 

An efficient procedure for the oxidation alcohols with PhI(OAc)2 in the presence of catalytic amounts of TEMPO (2,2,6,6-tetramethyl-l-piperidinyloxyl), originally developed by Piancatelli, Margarita and coworkers [143], has been frequently used in recent years [144-150]. This procedure works well for the 

R = Ph, 4-MeOC6H4,4-CIC6H4,4-NO2C6H4, C9H19, C7H15, PhCH2CH2, PhCH=CH, etc. 

A similar oxidative protocol has been used for the oxidation of (fluoroalkyl)alkanols, Rf(CH2) CH20H, to the respective aldehydes [146], in the one-pot selective oxidation/olefination of primary alcohols using the PhI(OAc)2-TEMPO system and stabilized phosphorus ylides [147] and in the chemo-enzymatic oxidation-hydrocyanation of 7,8-unsaturated alcohols [148]. Other [bis(acyloxy)iodo]arenes can be used instead of PhI(OAc)2 in the TEMPO-catalyzed oxidations, in particular the recyclable monomeric and the polymer-supported hypervalent iodine reagents (Chapter 5). Further modifications of this method include the use of polymer-supported TEMPO [151], fluorous-tagged TEMPO [152,153], ion-supported TEMPO [154] and TEMPO immobilized on silica [148], 

Based on the ability of the PhI(OAc)2-TEMPO system to selectively oxidize primary alcohols to the corresponding aldehydes in the presence of secondary alcohols, Forsyth and coworkers have developed the selective oxidative conversion of various highly functionalized l°,2°-l,5-diols into the corresponding 8-lactones [155]. A representative example, showing the conversion of substrate 127 into the 8-lactone 

An efficient and mild procedure has been described for the oxidation of different types of alcohols to carbonyl compounds using TEMPO as the catalyst and (dichloroiodo)benzene as a stoichiometric oxidant at 50 °C in chloroform solution in the presence of pyridine [157]. Under these conditions, 1,2-diols are oxidized to p-hydroxyketones or p-diketones depending upon the amount of PhICh used. Interestingly, a competitive study has shown that this system preferentially oxidizes aliphatic secondary alcohols over aliphatic primary alcohols [157], while the PhI(OAc)2-TEMPO system selectively converts primary alcohols into the corresponding aldehydes in the presence of secondary alcohols. 

Sulfoxides (essentially DMSO) can be used for oxidation of alcohols to carbonyl compounds as in the Moffatt, Swern and related oxidations [237, 238]. These mild and useful processes proceed through an oxosulfonium salt. In the Pfitzner-Moffatt procedure the alcohol is treated with DMSO, DCC and anhydrous phosphoric acid. The proposed mechanism involves an alkylsulfonium ylide as an intermediate. 

The enzyme cholesterol oxidase is an effective oxidation catalyst when used in a micellular system involving SCCO2 and water [25]. The use of a perfiuoropoly-ether-based surfactant causes the formation of reverse-micelles in which the 

Secondary alcohols are easily oxidized to give excellent yields of ketones. The chromic acid reagent is often best for laboratory oxidations of secondary alcohols. 

The chromic acid reagent is prepared by dissolving sodium dichromate, (Na2Cr20v) in a mixture of sulfuric acid and water. The active species in the mixture is probably chromic acid, H2Cr04, or the acid chromate ion, HCrO. Adding chromium trioxide (Cr03) to dilute sulfuric acid achieves the same result. 

The mechanism of chromic acid oxidation probably involves the formation of a chromate ester. Elimination of the chromate ester gives the ketone. In the elimination, the carbinol carbon retains its oxygen atom but loses its hydrogen and gains the second bond to oxygen. 

Elimination of the chromate ester and oxidation of the carbinol carbon 

Oxidation of a primary alcohol initially forms an aldehyde. Unlike a ketone, however, an aldehyde is easily oxidized further to give a carboxylic acid. 

Synthesis.— This section is again divided into routes requiring oxidation of alcohols, nucleophilic attack by oxygen at a saturated centre or by trapping of an intermediate consequent upon electrophilic attack at an unsaturated centre, and various cycloaddition reactions. 

Oxidation of Alcohols. Following the reaction of 2-methyladamantan-2-ol with lead tetra-acetate and iodine to give substituted oxa-adamantanes it is now found that adamantan 2-ol affords oxa-adamantane under similar 

Various microorganisms and isolated enzymes have also been used for the oxidation of alcohols (Fig. 10.16). For example, horse liver alcohol dehydrogenase was used for the 

Mono oxygenases, enzymes that transfer one oxygen atom to the substrate from molecular oxygen, and dioxygenases, enzymes that transfer both oxygen atoms from molecular oxygen, have been used for oxidations. Examples of such reactions are shown in Fig. 10.17.  

The oxidation of alchols can be readily carried out using peroxygen reagents. The extensive range of methods available makes it possible to achieve the oxidation of a wide variety of both aliphatic and aromatic primary and secondary alcohols, often in a highly selective manner. 

Direct activation methods are not normally successful for the oxidation of alcohols using hydrogen peroxide. An advantage of this is that alcohols can often be used as solvents for other oxidations, which do not use direct activation methods. However, hydroxy ketals can be cleaved with aqueous hydrogen peroxide, and the ene-diol of L-ascorbic acid can be oxidized with sodium perborate.185 Under the conditions employed, it is likely that the active oxidant is free hydrogen peroxide rather than any boron species. 

Peroxides may be used to oxidize alcohols, but additional activation is usually necessary for successful reaction to take place. An early example of this was the use of catalytic amounts of 2,2,6,6-tetramethylpiperidine hydrochloride 

Application of Hydrogen Peroxide for the Synthesis of Fine Chemicals 

A number of variations on the system, including the use of the nitroxyl radical of TMP-HCl187 and of perbenzoic acid,188 have been described. Unsaturated substrates are converted to epoxyketones.187 By adding excess peracid, further conversion of ketones to esters via Baeyer-Villiger re-arrangement is possible. MCPBA may be used to oxidize sterically unhindered, acid-stable alcohols in the presence of hydrochloric acid using dimethylformamide or tetrahydrofuran solvents.189 

There are a variety of products, depending upon the alcohol. Allylic and benzylic alcohols are easily oxidized under mild conditions. Secondary alcohols are oxidized under rather stronger conditions. Simple primary alcohols (i.e., not activated benzylic alcohols) are not oxidized. The oxidation of tertiary alcohols is accomplished with C-C bond fission. 

The last named is an example of a Grob oxidative fragmentation. 

Catalyst Glycerol (mmol) Glycerol/ Pq2 metal NaOH (bar) (mol ratio) (mmol) Glycerol Conversion (%) Selectivity (%)  

Comprehensive Organic Reactions in Aqueous Media, Second Edition, by Chao-Jun 

Recently, great advancement has been made in the use of air and oxygen as the oxidant for the oxidation of alcohols in aqueous media. Both transition-metal catalysts and organocatalysts have been developed. Complexes of various transition-metals such as cobalt, copper [Cu(l) and Cu(ll)], Fe(lll), Co/Mn/Br-system, Ru(lll and IV), and V0P04 2H20, have been used to catalyze aerobic oxidations of alcohols. Cu(l) complex-based catalytic aerobic oxidations provide a model of copper(l)-containing oxidase in nature. Palladium complexes such as water-soluble Pd-bathophenanthroline are selective catalysts for aerobic oxidation of a wide range of alcohols to aldehydes, ketones, and carboxylic acids in a biphasic 

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The standard redox potentials of inorganic oxidants used in organic synthesis are generally around or above + 1.0 V. Organic substrates do not have such high potentials. The values for the CH4/CH3OH and CjHj/CjHjOH couples are at +0,59 V and 0.52 V, respectively. The oxidation of alcohols and aldehydes corresponds to values around 0.0 V (W.M. 

Enone Formation from Ketones, and Oxidation of Alcohols... 

The final step can involve introduction of the amino group or of the carbonyl group. o-Nitrobenzyl aldehydes and ketones are useful intermediates which undergo cyclization and aromatization upon reduction. The carbonyl group can also be introduced by oxidation of alcohols or alkenes or by ozonolysis. There are also examples of preparing indoles from o-aminophcnyl-acetonitriles by partial reduction of the cyano group. 

Derivatives in which the substituents are already in a higher oxidation state than alkyl groups can be good precursors of acids. Acids can be prepared by the oxidation of alcohols. 

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... 

A major difference between alcohols and thiols concerns their oxidation We have seen earlier m this chapter that oxidation of alcohols gives compounds having carbonyl groups Analogous oxidation of thiols to compounds with C=S functions does not occur Only sulfur is oxidized not carbon and compounds containing sulfur m various oxida tion states are possible These include a series of acids classified as sulfemc sulfimc and sulfonic according to the number of oxygens attached to sulfur... 

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 ke tones... 

Chromium compounds decompose primary and secondary hydroperoxides to the corresponding carbonyl compounds, both homogeneously and heterogeneously (187—191). The mechanism of chromium catalyst interaction with hydroperoxides may involve generation of hexavalent chromium in the form of an alkyl chromate, which decomposes heterolyticaHy to give ketone (192). The oxidation of alcohol intermediates may also proceed through chromate ester intermediates (193). Therefore, chromium catalysis tends to increase the ketone alcohol ratio in the product (194,195). 

Petoxycatboxyhc acids have been obtained from the hydrolysis of stable o2onides with catboxyhc acids, pethydtolysis of acyhinida2ohdes, reaction of ketenes with hydrogen peroxide, electrochemical oxidation of alcohols and catboxyhc acids, and oxidation of catboxyhc acids with oxygen in the presence of o2one (181). 

This ladical-geneiating reaction has been used in synthetic apphcations, eg, aioyloxylation of olefins and aromatics, oxidation of alcohols to aldehydes, etc (52,187). Only alkyl radicals, R-, are produced from aliphatic diacyl peroxides, since decarboxylation occurs during or very shortiy after oxygen—oxygen bond scission in the transition state (187,188,199). For example, diacetyl peroxide is well known as a source of methyl radicals (206). 

The initiating step in these reactions is the attachment of a group to the sulfoxide oxygen to produce an activated intermediate (5). Suitable groups are proton, acyl, alkyl, or almost any of the groups that also initiate the oxidations of alcohols with DMSO (40,48). In a reaction, eg, the one between DMSO and acetic anhydride, the second step is removal of a proton from an a-carbon to give an yUde (6). Release of an acetate ion generates the sulfur-stabilized carbonium ion (7), and the addition of acetate ion to the carbonium ion (7) results in the product (eq. 15) ... 

Health and Safety Factors (Toxicology). Manufacture of cyanamide and calcium cyanamide does not present any serious health hazard. Ingestion of alcohoHc beverages by workmen within several hours of leaving work sometimes results in a vasomotor reaction known as cyanamide flush. Cyanamide interferes with the oxidation of alcohol and accumulation of acetaldehyde probably accounts for this temporary phenomenon. Although extremely unpleasant, it has not been known to result in serious illness or to have any permanent effect. 

Pyridinium chlorochromala 1 or Cr03-dimelhylpyrazola 4 for oxidation of alcohols to ketone or aldehydes... 

DESS - MARTIN Oxidizing Reagent Oxidation of alcohols to aldehydes or ketones by means of penodinanes. 

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