Oxidation of Alcohols, Enols, and Phenols

Problem 8.L With an alcohol of your own choice (which you should name and for which you should draw the structure), write the product of the reaction of that alcohol with 

Rnally, as anticipated from Table 8.4, alcohols are protonated by strong Brpnsted acids to form oxonium salts (Equation 8.6, producing ethyl oxonium chloride), and coordination of the electron pair on oxygen can also be effected by the reaction with Lewis acids (Equation 8.7, forming ethyl oxonium aluminum dichloride). 

In that regard, although methanol (methyl alcohol, CH3OH), which is quite toxic, is occasionally used in small quantities as a gasoline additive (often with other alcohols), the use of pure methanol as a fuel remains experimental. Indeed, most methanol is used to produce formaldehyde (methanal, H2C=0) or as an intermediate in other commercial endeavors vide infra). 

On the other hand, ethanol (ethyl alcohol, CH3CH2OH), which is less toxic, and which is largely made for industrial purposes by the acid-catalyzed hydration of ethene (ethylene, H2C=CH2, Chapter 6), has generated greater interest as a fuel for 

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Part I. The Reactions of Alcohols, Enols, and Phenols Oxidation, Reduction, Substitution, Addition, Elimination, and Rearrangement Part II. Ethers... 

Barton and co-workers have investigated the use of triarylbismuth dihalides and related compounds for synthetic purposes. These compounds can be used for the oxidation or arylation of a variety of alcohols, enols, amines, phenols, thiols, hydrazine, nitroalkanes and others (Sections 5.2.4, 5.4.3 and 5.5.2). 

Tetraphenylbismuth(V) compounds have been used as the oxidizing agents for alcohols under basic conditions (Section 5.2.4). They are also employed as the phenylating agent of alcohols, enols, amines, phenols, indoles, thiols, sulfinates, nitroalkanes, and others (Section 5.5.2). The selectivity between O- and C-arylations is dependent on the reaction conditions employed 2-naphthol is O-phenylated by tetraphenylbismuthonium trifluoroacetate under acidic conditions, whereas it is C-phenylated under basic conditions. 

A number of compounds react rapidly with DDQ at room temperature. They include allylic and benzylic alcohols, which can thus be selectively oxidized, and enols and phenols, which undergo coupling reactions or dehydrogenation, depending on their structure. Rapid reaction with DDQ is also often observed in compounds containing activated tertiary hydrogen atoms. The workup described here can be used in all these cases. 

The combination of Ti(OPr )4 and (BulO)2 or Bu 02I I has been utilized in a number of organic transformations including the Sharpless epoxidation,416 the conversion of alcohols to carbonyl compounds,417 the oxidation of phenols to quinones or ketols,418 and the oxidation of Ti enolates to o-hydroxyketones.419... 

In addition to the oxidation of aliphatic hydroxy compounds, aromatic derivatives that contain hydroxyl groups (phenol derivatives) can also be oxidized. The course of the oxidation differs in that the aromatic ring is disrupted, leading to quinones, important components in a variety of natural products.It is also possible to convert aromatic hydrocarbons to phenols by oxidation. Quinones are obtained by oxidation of phenols and a phenol can be very loosely viewed as an enol. Inclusion of this chemistry immediately after discussing the oxidation of alcohols to ketones, aldehydes, or acids is done with the goal of providing some continuity in studying the oxidation of hydroxyl compounds. 

An interesting variant involves the use of an allylic alcohol as the alkene component. In this process, re-oxidation of the catalyst is unnecessary since the cyclization occurs with /Uoxygen elimination of the incipient cr-Pd species to effect an SN2 type of ring closure. Both five- and six-membered oxacycles have been prepared in this fashion using enol, hemiacetal, and aliphatic alcohol nucleophiles.439,440 With a chiral allylic alcohol substrate, the initial 7r-complexation may be directed by the hydroxyl group,441 as demonstrated by the diastereoselective cyclization used in the synthesis of (—)-laulimalide (Equation (120)).442 Note that the oxypalladation takes place with syn-selectivity, in analogy with the cyclization of phenol nucleophiles (1vide supra). 

Strategies for preparing mixed, acyclic acetals on insoluble supports include the oxidative haloalkoxylation of support-bound enol ethers (Entry 6, Table 6.1) and the acid-catalyzed reaction of alcohols with resin-bound enol ethers [627]. Alternatively, resin-bound a-chloro ethers can be converted to mixed acetals by reaction with alcohols or phenols in the presence of strong bases (KO/Bu, HOfBu, DMF, 5 h) [550,628]. Polystyrene-bound a-(phenylseleno)ethers react with aliphatic alcohols under slightly acidic conditions (NIS, TfOH, DCM/dioxane (1 1), 0°C to 20 °C, 1 h) to yield mixed, acyclic acetals [628],... 

Not only alkenes and arenes but also other types of electron-rich compound can be oxidized by oxygen. Most organometallic reagents react with air, whereby either alkanes are formed by dimerization of the metal-bound alkyl groups (cuprates often react this way [80]) or peroxides or alcohols are formed [81, 82]. The alcohols result from disproportionation or reduction of the peroxides. Similarly, enolates, metalated nitriles, phenolates, enamines, and related compounds with nucleophilic carbon can react with oxygen by intermediate formation of carbon-centered radicals to yield dimers (Section 5.4.6 [83, 84]), peroxides, or alcohols. The oxidation of many organic compounds by air will, therefore, often proceed faster in the presence of bases (Scheme 3.21). 

Phenol annotation.1 A key step in a synthesis of the aglycone (4) of pseu-dopterosin A is a reaction of the silyl enol ether 2 with 2-butynal (1) and (CH3)3SiOTf at — 78° followed by PCC oxidation of the resulting propargylic alcohol to give 3 in 61% overall yield. 

As with phenols and enols, the reaction of alcoholic substrates with tetraphenylbismuthonium trifluoroacetate appeared to be pH dependent. The reactions of primary and secondary alcohols with tetraphenylbismuthonium trifluoroacetate or related tetraphenylbismuthonium reagents under basic conditions resulted in oxidation to the corresponding carbonyl derivatives. Under neutral or acidic conditions, the O-phenyl ethers of primary and secondary alcohols were obtained in modest yields (secondary alcohols) to fairly good yields (primary alcohols) by reaction of the alcohol with tetraphenylbismuthonium trifluoroacetate (6) in benzene or in toluene under reflux. Tertiary alcohols gave intractable mixtures. ... 

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