The oxidation of secondary alcohols

The oxidation of secondary alcohols with sodium dichromate in dilute sulphuric acid gives acceptable yields of ketones since these do not normally undergo extensive further oxidation under the reaction conditions (cf. Section 5.7.1, p. 587, the oxidation of primary alcohols to aldehydes). 

An excellent method for the conversion of ether-soluble secondary alcohols to the corresponding ketones is by chromic acid oxidation in a two-phase ether-water system. The reaction is carried out at 25-30 °C with the stoichiometric quantity of chromic acid calculated on the basis of the above equation, and is exemplified by the preparation of octan-2-one and cyclohexanone (Expt 5.86). The success of this procedure is evidently due to the rapid formation of the chromate ester of the alcohol, which is then extracted into the aqueous phase, followed by formation of the ketone which is then extracted back into the ether phase and is thus protected from undesirable side reactions. 

A slightly modified procedure - oxidation with 100 per cent excess of chromic acid at 0 °C for a short period - is adopted for strained bicyclic alcohols (e.g. the oxidation of ( —)-borneol to ( — )-camphor, Expt 5.87) and gives excellent yields of the corresponding ketones. Cycle ketones which are susceptible to add-catalysed epimerisation are moreover obtained by this procedure in a high degree of epimeric purity. 

The use of pyridinium-based chromium(vi) oxidising agents (cf. Section 5.7.1, p. 587) is illustrated by the use of the supported reagent, pyridinium chlorochromate-alumina, for the conversion of the cyclic allylic alcohol, carveol, into the corresponding a, / -unsaturated ketone, carvone125 (Expt 5.88). 

The conversion of an alkene into the corresponding ketone may be effected by means of a convenient sequence which involves hydroboration followed by oxidation with chromic acid of the resulting organoborane (cf. Section 5.4.3, 

---

A white solid, m.p. 178 C. Primarily of interest as a brominaling agent which will replace activated hydrogen atoms in benzylic or allylic positions, and also those on a carbon atom a to a carbonyl group. Activating influences can produce nuclear substitution in a benzene ring and certain heterocyclic compounds also used in the oxidation of secondary alcohols to ketones. 

By the oxidation of secondary alcohols with potassium dichromate and dilute sulphuric acid, for example ... 

Furthermore, the oxidation of secondary alcohols with an equimolar amount of BTMA Br3 in the presence of a buffer such as aq. Na2HP04 or aq. CH3COONa afforded the corresponding ketones in good yields (Fig. 23). 

The complex Pd-(-)-sparteine was also used as catalyst in an important reaction. Two groups have simultaneously and independently reported a closely related aerobic oxidative kinetic resolution of secondary alcohols. The oxidation of secondary alcohols is one of the most common and well-studied reactions in chemistry. Although excellent catalytic enantioselective methods exist for a variety of oxidation processes, such as epoxidation, dihydroxy-lation, and aziridination, there are relatively few catalytic enantioselective examples of alcohol oxidation. The two research teams were interested in the metal-catalyzed aerobic oxidation of alcohols to aldehydes and ketones and became involved in extending the scopes of these oxidations to asymmetric catalysis. 

Secondary alcohol oxidases catalyze the oxidation of secondary alcohols to ketones using molecular oxygen as oxidant. A secondary alcohol oxidase from polyvinyl alcohol-degrading bacterium Pseudomonas vesicularis var. povalolyticus PH exhibited activity toward several... 

N-bromosuccinimide is a selective oxidising agent and oxidises OH groups without disturbing other oxidisable groups. Thus while it does not oxidise aliphatic primary alcohols in presence of water it is highly selective for the oxidation of secondary alcohols to ketones. 

Thioanisolc. A system utilizing thio-anisole as an organic mediator was developed for the oxidation of secondary alcohols to ketones (Fig. 5 2-octanol to 2-octanone 99%, menthol to menthone 92%, cyclododecanol to cyclododecanone 75%) [43]. The use of 2,2,2-trifluoroethanol as a solvent in the mediatory system improved the yields [44]. 

TEMPO 2,2,6,6-Tetramethylpiperidinyl-1-oxy (20 TEMPO) works as a mediator for the oxidation of primary alcohols to aldehydes. The oxidation of secondary alcohols is much slower than that of primary alcohols as exemplified by the oxidation of (19) to (21) (Scheme 7) [48]. Active species is the oxo-ammonium generated from TEMPO. 

The oxidation of secondary alcohols (66) to (67) is possible by indirect electrooxidation utilizing thioanisole as an organic redox catalyst in a PhCN-2,6-lutidine-Et4NOTs-(C/Pt) system at 1.5 V vs. SCE (Scheme 25) [81] and is also performed in the presence of 2,2,2-trifluoroethanol [82]. It is suggested that the initially formed cation radical sulfide species derived from the direct discharge of the sulfide provides phenylmethyl-alkoxysulfonium ions, which are transformed to (67) and thioanisole. 

A-Hydroxyphthalimide (88) has also been shown to be an effective mediator for the oxidation of alcohols [120]. The oxidation process depicted in Scheme 32 is suitable for the oxidation of secondary alcohols (86). A-Hydroxyphthalimide also plays an important role as a mediator for deprotection of the 4-phenyl-l,3-dioxolane... 

The oxidations of secondary alcohols and sulfides by halamine polymers produce ketones and sulfoxides, respectively, with some sulfones and chlorosulfoxides produced in the latter case. A mechanism is proposed based on the oxidation kinetics. 

Oppenauer-type oxidation of secondary alcohols can be a convenient procedure for obtaining the corresponding carbonyl compounds. It was found recently [19], that Ir(I)- and Rh(I)-complexes of 2,2 -biquinoline-4,4 -dicarboxylic acid dipotassium salt (BQC) efficiently catalyze the oxidation of secondary alcohols with acetone in water/acetone 2/1 mixtures (Scheme 8.5). The reaction proceeds in the presence of Na2C03 and affords medium to excellent yields of the isolated ketones. The process is much faster in largely aqueous solutions, such as above, than in wet organic solvents in acetone, containing only 0.5 % water, low yields were observed (15 % vs. 76 % in case of cyclohexanol). 

The catalytic activity of Cp Ir(III) complexes in the Oppenauer-type oxidation of alcohols was considerably enhanced by the introduction of N-heterocyclic carbene ligands. Here, high turnover numbers (TONs) of up to 950 were achieved in the oxidation of secondary alcohols [40]. 

Hydrogen transfer reactions from an alcohol to a ketone (typically acetone) to produce a carbonyl compound (the so-caUed Oppenauer-type oxidation ) can be performed under mild and low-toxicity conditions, and with high selectivity when compared to conventional methods for oxidation using chromium and manganese reagents. While the traditional Oppenauer oxidation using aluminum alkoxide is accompanied by various side reactions, several transition-metal-catalyzed Oppenauer-type oxidations have been reported recently [27-29]. However, most of these are limited to the oxidation of secondary alcohols to ketones. 

A combination of bromide ions and methyl octyl sulphide is able to oxidise secondary alcohols at the potential necessary to fonn bromine. Conversion of the alcohol to the ketone follows the Scheme 8.2 and uses an undivided cell with benzo-nitrile as the solvent containing 2,6-lutidine as base and tetraethylamnionium bromide. The reaction occurs using a platinum anode at 1.1 V vs-, see [28], Thio-anisole alone, in absence of bromide, will function as a catalyst for the oxidation of secondary alcohols but in these cases a more positive anode potential of 1.5 V vs. see is needed to oxidise the thioether [29]. 

The nickel oxide electrode is generally useful for the oxidation of alkanols in a basic electrolyte (Tables 8.3 and 8.4). Reactions are generally carrried out in an undivided cell at constant current and with a stainless steel cathode. Water-soluble primary alcohols give the carboxylic acid in good yields. Water insoluble alcohols are oxidised to the carboxylic acid as an emulsion. Short chain primary alcohols are effectively oxidised at room temperature whereas around 70 is required for the oxidation of long chain or branched chain primary alcohols. The oxidation of secondary alcohols to ketones is carried out in 50 % tert-butanol as solvent [59], y-Lactones, such as 10, can be oxidised to the ketoacid in aqueous sodium hydroxide [59]. 

The oxidation of alcohols to aldehydes and ketones using catalytic amounts of TEMPO and controlled potential electrolysis has been reported, including the observation of a special selectivity for primary alcohols in the presence of secondary alcohols (equation 20) °. The oxidation of secondary alcohol is much slower than that of primary alcohols. This method is especially effective for oxidation of the primary alcohol group in carbohydrates (equations 21 and 22) . ... 

There are some reports of kinetic investigations of Ru-catalysed oxidations in which the nature of the active catalyst or catalyst precursor is unclear but which may be predominantly [RuO ] . Two papers used electronic or Raman spectroscopy to identify such species [212], [222]. Examples in which [RuO ]" has been shown to be the active species or catalyst precursor in the oxidation of secondary alcohols to ketones include... 

RuCl2(picphen)]Cl (picphen=few(picolinaldehyde)-(9-phenylenedi-imine) is made by condensation of picolinaldehyde and o-phenylenediamine) and the resulting Schiff base then treated with RuClj in ethanol. Kinetics were followed of the oxidation of secondary alcohols (benzhydrol, 1-phenylethanol and a-tetralol) to the corresponding ketones by [RuCl2(picphen)] "/NMO or Tl(OAc)3/water/30°C. The intermediacy of a Ru(V) oxo species was suggested [800]. 

More recently, it was found that the incorporation of N-heterocychc car-bene ligands to the Cp lr moiety (Eq. 12) considerably enhances catalyst activity for alcohol oxidation reactions [50,51]. By way of example, the oxidation of secondary alcohols occurs with high turnovers, up to 3,200 for the oxidation of 1-phenylethanol and 6,640 for that of cyclopentanol (95% yield, 40 °C, 4 h) using the complex with the carbene derived from the tetram-ethyhmidazole (Eq. 12). 

The oxidation of secondary alcohols by oxygen may be represented by the following chain reaction mechanism. 

A new, selective and efficient alternative method has been developed for the oxidation of secondary alcohols to ketones in moderate to good yields in hydrated media. Table 5.3 shows different substrates that can be selectively oxidized under the reaction conditions. 

A recent report (J. Org. Chem. 2004, 69, 8510) by Paul G. Williard of Brown University and Ruggero Curci of University di Bara of the oxidation of 5 to 6 serves as a timely reminder that the widely-used epoxidation reagent dimethyl dioxirane is also useful for the oxidation of secondary alcohols to ketones. 

Indirect electrochemical oxidations using the nitrate ion as redox catalyst proceed via the electro-generated NOj radical. They are useful for the oxidation of secondary alcohols and of alkyl aromatic compounds in the side-chain... 

The hypofluorous acid/acetonitrile complex has also been used for the oxidation of secondary alcohols and for the Baeyer Villiger oxidation of ketones.24-25... 

---