Oxidizing Agents for Alcohols

Alcohols are often oxidized with chromium(VI) compounds. When the alcohol is oxidized, Cr(VI) is reduced in several steps to Cr(III). The specific Cr(VI) species used depends on the scale of the process, the cost of reagents, and limitations that result firom the presence of other functional groups in the reactant. For example, the inexpensive reagent sodium dichromate (Na2Cr207) oxidizes secondary alcohols to ketones. It also oxidizes primary alcohols to aldehydes and then to carboxylic acids. Sodium dichromate in acetic acid (HOAc) is used in large-scale reactions to convert secondary alcohols to ketones. 

In small-scale reactions, the Jones reagent, which consists of chromium trioxide (CrO in a solution of aqueous acetone and sulfuric acid, is used to oxidize alcohols. The Jones reagent converts primary alcohols to aldehydes and then immediately oxidizes the aldehydes to carboxylic acids. It also converts secondary alcohols to ketones. 

Oxidation by the Jones reagent occurs rapidly at or below room temperature. A simple alcohol with no other functional groups is easily oxidized to give a good yield of oxidized product. 

Alcohols are also oxidized with a milder oxidizing agent consisting of pyridinium chloro-chromate (PCC) in methylene chloride (CH Cy as solvent. PCC is made by dissolving CrO in HCl and then adding pyridine to obtain a sohd, which is isolated and then dissolved in methylene chloride. The reagent is anhydrous, so a primary alcohol can be converted to an aldehyde without further oxidation to a carboxylic acid. 

Because the PCC reaction occurs under basic conditions, functional groups such as carbon—carbon double bonds do not react during the time requited for oxidation of the alcohol. But, the principal advantage of PCC is that primary alcohols are converted to aldehydes without continued oxidation to carboxylic acids. 

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Pyrazine 1-oxide gave 4-oxidopyrazinium chlorochromate (309) (Cr03, HC1, 20°C 70%) for comparison, pyrazine gave the 1 1 complex (310) (Cr03, CH2C12, N2, 20 — 0°C, 4 h 55%). Both products proved to be mild oxidizing agents for alcohols.279... 

PDC with tiimethylsilyl chloride s is not only a rapid oxidizing agent for alcohols, but will also effect a deprotection-oxidiation sequence for silyl ethers. Both trimethylsilyl and r-butyldimethylsilyl ethers, which are normally stable to PDC, can be transformed directly into the corresponding carbonyl compounds in good yield (Table 13). 

Chromium(VI) oxide in various solvent systems provides an excellent oxidizing agent for alcohols, since it rapidly forms chromate esters which are intermediates in the oxidation of alcohols to aldehydes and ketones. The oxidation of [2- H]propan-2-ol showed a significant isotope effect when compared to propan-2-ol. Hence the abstraction of a proton by a base in the fragmentation of these esters is the rate-determining step in the reaction (Scheme 2.19). 

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. 

Oxidation. The reagents Ar3Bi=NTs are formed quantitatively from Ar Bi and PhI=NTs in dichloromethane at room temperature. They are mild oxidizing agents for alcohols. 

A common laboratory oxidizing agent for alcohols is chromic anhydride, Cr03, dissolved in aqueous sulfuric acid (Jones reagent). Acetone is used as a solvent in such oxidations. Typical examples are... 

In the search for specific and gentle oxidizing agents for alcohols that leave other functional groups unaffected, it has been found that reduction of the common solvent, methylsulfinylmethane (dimethyl sulfoxide [DMSO] [( 3)280]) to dimethyl sulfide can be very useful. Thus, both items 6 and 7 in Table 8.5, the MofEatt oxidation and the Swern oxidation, respectively, which can be performed with exquisite selectivity at low to moderate temperatures, have found wide use. 

Magnesium methylate is used as a drying agent for alcohols and other organic solvents and as an intermediate in various manufacturing processes, eg, for organomagnesium compounds (79), orthocarbonic esters (80), and for oxide coatings. 

There are a number of methods for the oxidation of primary alcohols or ethers to dimeric esters, and secondary alcohols to ketones. We recently also found that quaternary ammonium tribromides, especially BTMA Br3, are useful oxidizing agents for the purpose described above (ref. 31). 

Chromium(VI) oxide is used for chromium plating copper stripping as an oxidizing agent for conversion of secondary alcohols into ketones (Jones oxidation) as a corrosion inhibitor in purification of oil and in chromic mixtures for cleaning laboratory glassware. 

Several other polymer-bound oxidizing reagents have recently been reported in the literature (reaction 14). A polyethyleneimine-supported silver dichromate 35 has been shown to be a stable, mild, and efficient oxidizing agent for the conversion of alcohols to carbonyl compounds.51 A... 

This is a mild oxidizing agent for conversion of primary alcohols to aldehydes and secondary alcohols to ketones. 

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. 

It has been demonstrated that the oxidation of alcohols with hexacyanoferrate(III) (HCF) shows a hyperbolic variation with HCF concentration, and the reaction order varies from one to zero on increasing the HCF concentration. This rate law is obeyed during the initial moments of the reaction and at any subsequent time. These results rule out the possibility that any substance produced during the course of the reaction acts as an activator or inhibitor of the reaction rate. The mixed order has been attributed to the comparable rates of complex decomposition and catalyst regeneration steps.86 HCF acts as a selective oxidizing agent for the oxidation of catechols even in the presence of 2-mercaptobenzoxazole, as an easily oxidizable thiol, to produce related catechol thio ethers.87 Hexacyanoferrate(II) has a retarding effect on the oxidation of vanillin with HCF in alkaline solutions. A mechanism based on the observed kinetics has been proposed 88... 

Bis[4-methoxyphenyl] tellurium oxide was found to be a mild and highly selective oxidizing agent for the conversion of thiocarbonyl groups to carbonyl groups, thiols to disulfides, arylhydrazines to arenes, and 1,2- or 1,4-dihydroxyarenes to quinones. No reaction was observed with simple phenols, alcohols, enamines, amines (including pyrrole, indole, tryptophan, tyrosine, aniline, and dimethylaniline), oximes, dithiolanes, isonitriles, and 2,4-dinitrophenylhydrazones4. 

The treatment of isatin with sodium hypochlorite in acetic acid leads to 1-chloroisatin, an effective mild oxidizing agent for the conversion of alcohols to aldehydes and ketones110 and of indoles to 3-chloroindoles without formation of by-products111. N-[phenyliodine(III)] bisisatin can be obtained from the sodium salt of isatin and phenyliodine (IE) bistrifluoroacetate in 85% yield. This compound is a member of a group of iodine(III)imides,... 

Sarett and coworkers discovered that the complex (1) prepared by the addition of chromium(VI) oxide to pyridine (CAUTION—reverse order of addition may cause the mixture to inflame) is an efficient oxidizing agent for the preparation of ketones from secondary alcohols. The reagent, as prepared by Sarett, is moderately soluble in pyridine, but is only sparingly soluble in standard organic solvents. Thus the normal procedure is to add a solution of the dcohol in pyridine to three equivalents of the complex, also in pyrictoe. This procedure is also useful for the preparation of aromatic and a, -unsaturated aldehydes, but the use of pyridine as solvent prohibits the oxidation of volatile, saturated primary alcohols. ... 

Manganese dioxide is extensively used as an oxidizing agent for the oxidation of allylic alcohols to the corresponding aldehydes. Benzylic and unactivated alcohols are also oxidized by Mn02-... 

Selenium dioxide (SeOi) oxidation Selenium dioxide is an excellent oxidizing agent for the oxidation of allylic and benzylic C-H fragments to allylic or benzylic alcohol. It also oxidizes the aldehydes and ketones to 1,2-dicarbonyl compounds (i.e. oxidation of active methylene groups to carbonyl groups). 

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