2.1 Catalytic studies

The present study was motivated by the accidental discovery that commercially available technical activated MnO₂ (Aldrich: activated, >90%, reference 63548-250G-F) affects the determination of the conversions during kinetic monitoring of alcohol oxidation by TBHP. A frequently used procedure to quench the excess oxidant, typically H₂O₂ [5] but also TBHP [6], involves the treatment of the withdrawn reaction mixture aliquots with excess MnO₂ before gas-chromatographic or NMR quantification of conversion. In an experiment where 1-phenylethanol (1a) was oxidized with 2 equivalents of TBHP in the presence of a molybdenum catalyst, we obtained erratic and non-reproducible conversions as a function of time. These results interrogated us on the role of MnO₂ as a stoichiometric oxidant or as an oxidation catalyst during the TBHP quenching phase. We therefore proceeded to study the same oxidation process in the presence of various amounts of the above-mentioned, commercially available MnO₂ (Table 1). When using one equivalent of MnO₂ (entry 1), a high substrate conversion was observed after 7 h at room temperature. The amount of MnO₂ could be limited to 20 mol%, proving its catalytic role in the reaction, but longer reaction times were needed to obtain high conversions (entries 2–3). The amount could be further decreased to 5 mol% but the reaction was rather slow even at 40 °C (entries 4–5). At 80 °C, good conversions and yields could be obtained limiting the amount of MnO₂ to 10 mol% and the reaction time to 7 h (entry 6). We also checked another MnO₂ source, more precisely a purer product although non-activated (ReagentPlus^® Sigma-Aldrich, ≥ 99%) (see Table 1, entry 7). This ReagentPlus^® MnO₂ exhibited a very low catalytic activity. We checked also that both the catalyst and oxidant are essential to the reactivity. Negligible conversion was observed when using TBHP/decane in the absence of MnO₂ (entry 8). However, MnO₂ alone was able to slowly consume 1-phenylethanol as a stoichiometric oxidant and transform it into acetophenone with good selectivity (entries 9–10). The use of TBHP as the commercially available aqueous solution also gave good results (entry 11). This shows that the presence of water in the system does not negatively affect the reaction. Finally, we attempted to use hydrogen peroxide, a greener oxidant generating only water as a by-product [7], in place of TBHP but neither substrate conversion nor acetophenone formation were observed (entry 12). In this experiment, we presume that the catalase activity (disproportionation of H₂O₂ to H₂O and O₂ catalyzed by manganese compounds [8], including MnO₂ [9]) is faster than O atom transfer to the alcohol substrate. Finally, we carried out a catalyst recycling experiment. At the end of the reaction, MnO₂ was collected at the bottom of the reaction vessel by centrifugation, carefully washed with the reaction solvent (acetonitrile/toluene mixture) after the removal of the organic solution, and reused by adding a fresh acetonitrile/toluene solution containing 1-phenylethanol and TBHP (see entry 13). Indeed, MnO₂ was still active in the recycle run but with a significant decrease of the catalytic activity.

The substrate scope of this catalytic system was subsequently explored (the investigated substrate transformations are summarized in Scheme 1 and the results are collected in Tables 2 and 3). In all the studied cases, the presence of MnO₂ substantially increases the reaction rate (cf. the experiments run at 40 °C with the corresponding blank reactions run in the absence of MnO₂, i.e. entries 18, 24, 29, 35, 44 and 47). We first investigated primary benzylic alcohols (2a) and (3a) (Table 2). These alcohols proved a little more difficult to oxidize than the secondary benzylic alcohol (1a) (entries 16–17 and 22–23 versus entry 5 in Table 1) but their transformation into the corresponding aldehydes was efficient using 1 equivalent of the catalyst at RT (entries 14–15 and 19–21). On the other hand, the aldehyde product yield decreased at long reaction times due to further oxidation under these conditions. 4-methoxybenzaldehyde (3b) was consumed much faster than 4-methylbenzaldehyde (2b). Similar results were obtained for the oxidation of the allylic alcohol (4a) (entries 25–26), the rate of consumption of the cinnamaldehyde product (4b) being similar to that of (2b). The withdrawn aliquots for entries 25 and 26, after removing the solid MnO₂ by filtration but remaining in the presence of residual TBHP, showed a decrease of the (4b) product upon reinjection into the GC after 24 days. This decrease, however, is much slower than in the reaction in the presence of solid MnO₂ and is probably attributed to traces of soluble manganese compounds. Non-activated substrates like cyclohexanol, (5a), can also be oxidized (entries 30–34), although more slowly than the activated ones. Better results could be obtained at a slightly higher temperature (60 °C, entry 34), while using one equivalent of MnO₂ at room temperature results in low conversions (entries 30 and 31).

The catalytic system was then tested for the oxidation of alcohols from biomass (Table 3). For the oxidation of menthol (6a), whatever conditions were tried, no satisfactory yields of menthone could be obtained (entries 36–41). In particular, increasing the amount of catalyst from 0.05 to 1 equivalent or raising the temperature from 40 °C to 80 °C did not significantly improve the substrate conversion. The more activated perillyl alcohol (7a) and myrtenol (8a), on the other hand, were oxidized with relatively good conversions using 1 equivalent of MnO₂ at room temperature (entries 42–43 and 45–46) but afforded the corresponding aldehydes (7b) and (8b) with moderate selectivities and with slow erosion of the yield at longer reaction times, like for the other aldehyde products, (2b), (3b) and (4b), discussed above.

Since one possible cause for the poor performance of this system for less reactive alcohols is the competing MnO₂-catalyzed TBHP disproportionation (see next section), we have also investigated the oxidation of menthol with slow addition of the substrate via a syringe pump (complete addition of 2.4 equiv of TBHP in 15 h), under conditions otherwise identical to those of run 36–37 (40 °C, substr./MnO₂ = 1/0.05). The results of this experiment, see Fig. 1, demonstrate that this stratagem does not significantly improve the system performance, since a conversion of only 13% was measured after 48 h.

2.2 Mechanistic investigations

From the catalytic results presented above, it is clear that MnO₂ is able to catalyze the oxidation of alcohols to carbonyl products at rates that are competitive with those of the TBHP disproportionation. It was therefore important to evaluate the rate of TBHP disproportionation under the conditions used for the alcohol oxidation. From the results shown in Fig. 2, it is clear that the TBHP disproportionation process is catalyzed by MnO₂ (faster decay in the presence of a greater MnO₂ amount) but is indeed relatively slow, in agreement with the observed parallel catalytic action for alcohol oxidation. However, the catalase activity is relatively important. Thus, this system becomes interesting for the practical application to the catalytic oxidation of organic substrates only if the substrates can be oxidized extensively in a relatively short time, efficiently competing with the TBHP disproportionation process. This justifies the better results obtained with the benzylic and allylic alcohols.

4.1 - General considerations

MnO₂ was purchased from Aldrich (activated, >90%, reference 63548-250G-F) and used as received without any special precaution or further activation procedure. A second batch of MnO₂ (Sigma–Aldrich, ReagentPlus^®, reference 243442, ≥ 99%) was also tested (Table 1, entry 7). The tBuOOH solutions in decane (5.3 M, Aldrich) and in water (70%, Acros) and the H₂O₂ solution (30 wt % in water, Aldrich) were used as received. The substrates were purchased from commercial sources and used as received: phenylethanol (Aldrich, 98%), 4-methyl benzyl alcohol (Aldrich, 98%), 4-methoxy benzyl alcohol (Acros, 98%), trans-cinnamyl alcohol (Acros, 98%), cyclohexanol (Aldrich, 99%), menthol (Aldrich, 99%), perillyl alcohol (Aldrich, 96%), and myrtenol (Aldrich, 95%). The solvents (MeCN, toluene) were of analytical grade and were dehydrated on molecular sieves (4A) prior to use. Conversions for the oxidation experiments were determined by GC, using a Fisons 8130 instrument equipped with a DB-1MS capillary column (30 m × 0.32 mm × 0.25 μm) and with a flame ionization detector.

4.2 - General procedure for the oxidations of alcohols

The alcohol (1.2 mmol) of interest was dissolved in a mixture of acetonitrile (3 ml) and toluene (1 ml) for the experiments with TBHP/decane (or in 4 ml of acetonitrile for the experiments with TBHP/H₂O) and the desired amount of MnO₂ (see Tables) was added to the solution. Then tert-butyl hydroperoxide (TBHP, as a 5.3 M solution in decane, 453 μL, 2.4 mmol) was added to the reaction mixture, which was set at the desired reaction temperature with magnetic stirring in air. Aliquots (0.2 ml) were withdrawn at different time intervals, diluted with 1 ml of diethyl ether and filtered through a Pasteur pipette filled up with silica to eliminate the residual MnO₂. The silica was washed with 2 ml of diethyl ether. The resulting organic phase was analyzed by gas chromatography using diethyleneglycol dibutyl ether as an external standard.