Oxidation of Secondary Alcohol Functions

Although oxidation of secondary alcohol functions is usually an unwanted side-reaction occuiring during the oxidation of primary alcohols, some occur with high selectivity and lead to valuable products. 

In a similar investigation, Besson et al. [45] found that addition of bismuth to platinum had a similar effect. As in the previous investigation, however, the reaction was conducted at basic pH, and the yield of 2-keto-D-gluconate was limited by the formation of degradation products. 

Patents on oxidation of gluconic acid to 2-keto-D-gluconic acid on PtBi catalysts and on PtPb catalysts have been issued to Abbadi et al. [67] and Cerestar [68], respectively they use essentially the same reaction conditions as those described elsewhere [32]. 

Heinen et al. [35] investigated the oxidation of D-fructose on Pt/C catalyst at 30 °C and pH 7.3. Oxidation of both the C, primary alcohol and the C5 secondary alcohol occurred. The reaction stopped at ca 80 % conversion giving mainly 2-keto-D-gluconic acid (45% selectivity) and D-t/n-eo-hexo-2,5-diulose or 5-ketofructose (27 % selectivity). In the presence of bismuth-promoted catalysts selectivity to the former was slightly increased. This was attributed to the complexation by bismuth of the y9-o-fructofuranose stmcture via the c/s-diol functions. 

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The aerobic system TPAP/O /PMS/CH Cl was used to oxidise primary and secondary alcohols [28]. Oxidation of secondary alcohol functions in 3p-hydroxy-A-cholestenes,... 

According to Heinz et al. [1,2] the rate of oxidation with molecular oxygen on platinum catalysts follows the sequence CHO > CH2OH > CHOH, although Bi or Pb promoters could favor the oxidation of secondary alcohol function in acidic media (see Section 9.2.2.3). 

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]. 

One of die most common methods for the preparation of ketones is by the oxidation of secondary alcohols. The use of chromic acid (Jones reagent) is easy, safe, and effective for the oxidation of secondary alcohols to ketones. Furthermore Jones reagent gives a nearly neutral solution and thus can be used with a variety of acid-sensitive functional groups. 

The preceding section dealt specifically with the chemoselective oxidation of secondary/jprimary diols. There is a clear interest in chemoselective oxidation of secondary alcohols in the presence of other sensitive functional groups, and some of the methods available will be described briefly in this section. 

This system found another application—the oxidation of secondary alcohols into ketones in excellent yield. It is worthy of note that the oxidation procedure tolerates other functional groups including iodide, ester, terminal alkyne, aromatic ether, and 1,3-dioxolane. Certain secondary allylic alcohol such as 2-cyclododecen-l-ol (31) produced the corresponding epoxy ketone 32 in one pot, as exemplified in Sch. 17. 

If a secondary alcohol is not easily oxidized by other methods the ruthenium(Vin) oxide catalyzed procedure is often recommended. As mentioned previously, this is a strong oxidation method which is not compatible with a number of functional groups. Sodium periodate usually serves as the stoichiometric oxidant, but sodium hypochlorite has also been used in the oxidation of secondary alcohols [94]. Because of the cheap oxidants and a straightforward work-up this reaction is well suited for large-scale oxidations [95]. The TEMPO procedure also employs a cheap stoichiometric oxidant and has been applied in the oxidation of 23 on a kilogram scale [87]. The TPAP-catalyzed method is a milder procedure and many functional groups are stable to these conditions. However, secondary alcohols are still oxidized to ketones in high yield with NMO as the co-oxidant [24]. 

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. 

Molybdenum and vanadium compovmds have also been widely investigated as catalysts for the oxidation of alcohols with tert-butyl hydroperoxide (TBHP) as the oxidant. With the former a peroxometal pathway is involved while with the latter an oxovanadium(V) intermediate is the active oxidant. As with the H202-based systems described above, these systems exhibit a preference for the oxidation of secondary hydroxyl functionalities over primary ones. In contrast, zirconyl acetate, SO(OAc)2, catalyzes the selective oxidation of primary alcohol moieties with TBHP (Reaction 29) °". ... 

Aldehydes and ketones are among the most important of all functional groups, both in the chemical industry and in biological pathways, in this chapter, we ve looked at some of their typical reactions. Aldehydes are normally prepared in the laboratory by oxidation of primary alcohols or by partial reduction of esters. Ketones are similarly prepared by oxidation of secondary alcohols. 

Probably related mechanistically to the Oppenauer oxidations are several methods for oxidation that involve transfer of hydrogen to trichloroacetaldehyde. The reaction is mediated by alumina and is carried out by simply mixing the alcohol to be oxidized, the hydrogen acceptor, and alumina in an inert solvent. This reaction is suitable for selective oxidation of secondary alcohols in the presence of primary alcohols (which do not react) and also for the oxidation of compounds containing other easily oxidized functional groups. 

Earlier in this section, we saw that primary alcohols can oxidize to aldehydes. Aldehydes oxidize further by the addition of another O to form a carboxylic acid, which has a carboxyl functional group. This step occurs so readily that it is often difficult to isolate the aldehyde product during the oxidation reaction. In contrast, ketones produced by the oxidation of secondary alcohols do not undergo further oxidation. 

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