Oxidation secondary alcohols

Acetoin consumes 4 equivalents of V(V) to produce some biacetyl via C-H fission however, this cleavage is not accompanied by a hydronium-ion concentration dependence of the rate thereby differing from a secondary alcohol oxidation. The mechanism of breakdown of the complex is depicted as follows... 

Various experimental conditions have been used for oxidations of alcohols by Cr(VI) on a laboratory scale, and several examples are shown in Scheme 12.1. Entry 1 is an example of oxidation of a primary alcohol to an aldehyde. The propanal is distilled from the reaction mixture as oxidation proceeds, which minimizes overoxidation. For secondary alcohols, oxidation can be done by addition of an acidic aqueous solution containing chromic acid (known as Jones reagent) to an acetone solution of the alcohol. Oxidation normally occurs rapidly, and overoxidation is minimal. In acetone solution, the reduced chromium salts precipitate and the reaction solution can be decanted. Entries 2 to 4 in Scheme 12.1 are examples of this method. 

Reaction rates proceed according to the following trend secondary alcohols oxidize faster than primary, which oxidize much faster than methanol, which is unique. Methanol is slowly oxidized, presumably because it complexes strongly with the active Ti site. Moreover, methanol acts as a co-catalyst, increasing the rates of alkene4,37 and alkane51 oxidations. Thus methanol is a... 

Another factor complicating the situation in composition of peroxyl radicals propagating chain oxidation of alcohol is the production of carbonyl compounds due to alcohol oxidation. As a result of alcohol oxidation, ketones are formed from the secondary alcohol oxidation and aldehydes from the primary alcohols [8,9], Hydroperoxide radicals are added to carbonyl compounds with the formation of alkylhydroxyperoxyl radical. This addition is reversible. 

Both primeiry and secondary alcohols can be oxidized, but tertiary alcohols won t undergo simple oxidation. Oxidation of a primary alcohol gives an aldehyde however, preventing further oxidation of the aldehyde to a carboxylic acid is difficult. Secondary alcohols oxidize to a ketone without the problem of additional oxidation occurring. 

For a synthesis of the anti-cancer drug taxol TPAP/NMO was used in three steps, two for oxidation of primary alcohols to aldehydes (by TPAP/NMO/PMS/ CHjClj) and one for a secondary alcohol to ketone (by TPAP/NMO/PMS/CHjClj-CHjCN) [66], cf. also [111] and for the SERCA inhibitor thapsigargin (two primary alcohol and one secondary alcohol oxidation steps) [112], This system was also used during synthesis of the cholesterol biosynthesis inhibitor 1233A [52], the antibiotic and anti-parasitic ionophore tetronasin [113, 114] and for the cytotoxic sponge alkaloids motopuramines A and B [115]. 

Natural Product/Pharmaceutical Syntheses Involving Secondary Alcohol Oxidations... 

For the cw-dihydroxylation of protected lL-l,2 3,4-di-0-isopropylidenecyclohex-5-ene-l,2,3,4-tetrol (22g) to the diol lD-l,2 3,4-di-0-isopropylidene-a/to-inositol by RuClj/aq. Na(IO )/EtOAc-CH3CN/0°C cf. 3.1.2.1 and Fig. 3.3 [347]. Oxygen insertion by stoich. RuO /CCl occurred in addition to the secondary alcohol oxidation of the five-membered ring 5-0-benzoyl-l,2-0-isopropylidene-a-D-xylofnranose, giving the six-membered ring l,2-0-isopropylidene-6-0-benzoyl-3-oxa-a-D-e/7fftro -4-hexulopyranose-a-D-xylofuranose [325]. 

In this report a number of additional examples of primary and secondary alcohol oxidations are provided. 

The kinetics of secondary alcohol oxidation has been investigated with various reactants. When 2-octanol is oxidized with acetone solvent in the presence of excess reactant, the reaction is first-order with respect to H2O2 and zero-order with respect to the alcohol. Typical results are presented in Fig. 21. 

Primary alcohols oxidize to aldehydes, which, in turn, oxidize to carboxylic acids. Secondary alcohols oxidize to ketones. In each case, the reverse process is called re- duction... 

Bomeol, the structure of which is given in text Figure 26.7, is a secondary alcohol. Oxidation of bomeol converts it to the ketone camphor. 

One rare exception appears to be KOBu8. For example, the aerobic oxidation of 2-undecanol (5 mol% CuCl Phen, 5 mol% KOBu8, toluene, 80-90°C) afforded 2-unde-canone in almost quantitative yields. However, this system appears, so far, to be limited to secondary alcohol oxidations. 

The Irm complex [Cp+IrClf jl Cl) ] 2 serves as a catalyst for the oxidation of primary and secondary alcohols oxidation in acetone as the solvent [63]. The moderate effectiveness of this catalyst, however, prompted the preparation of several Ir111 analogs bearing an NHC ligand [58-60] (Scheme 7). It... 

Conversely, as previously stated, the aldehydes on reduction yield the primary alcohols and in the case of benzaldehyde, which is a commonly occurring substance in oil of bitter almonds, this method is used in the preparation of the alcohol. In the case of the secondary alcohols oxidation to ketones is not easily accomplished but the reverse reaction, the reduction of the ketones to secondary alcohols does take place with ease. 

Primary and secondary alcohols appear to oxidize rapidly to the corresponding carbonyl compounds with good efficiencies [10]. The initial point of attack is predominantly on the hydrogen on the carbinol carbon atom. Tertiary alcohols do not have a hydrogen in this position and are relatively resistant to oxidation. Alcohols, like aldehydes, are usually important intermediates in paraffin oxidations [18]. They undergo subsequent oxidation somewhat less readily than aldehydes, but primary and secondary alcohols oxidize much faster than the starting paraffin(s). Quite unlike aldehydes, however, alcohols do not, in general, autoxidize readily by themselves. Moreover, the deliberate addition of alcohol to an oxidation can slow or even stop the reaction [10, 19-21]. 

Reaction of the C-0 and O-H Bonds Primary alcohols oxidize to carboxylic acids secondary alcohols oxidize to ketones with chromium trioxide or sodium dichromate. Tertiary alcohols do not oxidize under mild conditions. With pyridinium chlorochromate (PCC) the oxidation of primary alcohols can be stopped at aldehydes. 

OxidationThe reagent oxidizes primary alcohols in good yield to aldehydes it can also oxidize aldehydes further to carboxylic acids. Ketones are obtained in high yield from secondary alcohols. Oxidation is most rapid in DMSO but proceeds satisfactorily in water. Hydroquinone is oxidized to p-benzoquinone in 89% yield. 

Oxidation. The title compound is an oxidant for primary and secondary alcohols. Oxidation is carried out with the base tetramethylguanidine at room temperature, liberating mesitylene and PhsBi as side products. 

Oxidation of Secondary Alcohols Oxidation of Insoluble Secondary Alcohols... 

To test the proposed route we capitalized upon our ability to use the intramolecular diyl trapping reaction to synthesize 95, the mono-ketal analog of 143. Ozonolytic cleavage of the C-C n bond of 95 followed by reduction with NaBIfy afforded diol 145 in an 85% yield. The primary alcohol was selectively protected as a silyl ether, and the secondary alcohol oxidized with PCC to provide ketone 146 as a 1 1 mixture of diastereomers. 

Many methods have been developed for the oxidation of primary and secondary alcohols. Oxidation of secondary alcohols normally gives rise to ketone products, whereas primary alcohols form aldehydes or carboxylic acids, depending on the reagent and conditions. Selective oxidation reactions have been developed that give these different types of products, even in the presence of other sensitive functionality. This section will describe, in turn, the different reagents used for the formation of aldehydes and ketones, before discussing the formation of carboxylic acids. 

The control of the configuration of the side chain at C-8 in a synthesis of C-gly-coside antibiotic pseudonomic acid 212 described by DeShong [46] resulted from a Claisen-Johnson rearrangement Dihydropyrane derivatives 213-214 after treatment with triethyl orthoacetate afforded an inseparable mixture of diastereomers. The anomeric center was then reduced and the side chain secondary alcohol oxidized. Diastereomeric ketones 215 and 216 were isolated at this stage in a 2 1 ratio (Scheme 6.33). 

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