Mónica
Carril
a,
Philipp
Altmann
a,
Werner
Bonrath
b,
Thomas
Netscher
b,
Jan
Schütz
b and
Fritz E.
Kühn
*a
aMolecular Catalysis, Catalysis Research Center, Technische Universität München, Ernst-Otto-Fischer-Straße 1, D-85747 Garching bei München, Germany. E-mail: fritz.kuehn@ch.tum.de; Tel: +49 89 289 13081
bDSM Nutritional Products, Research and Development, P. O. Box 2676, 4002 Basel, Switzerland
First published on 21st October 2011
Vitamin E is an essential food component and antioxidant of major economic relevance. 2,3,5-Trimethyl-1,4-benzoquinone is a key intermediate in the production of vitamin E, which can now be selectively achieved through MTO-catalysed oxidation of simple and inexpensive pseudocumene (1,2,4-trimethylbenzene), in the presence of hydrogen peroxide and an appropriate amphiphile.
Hence, given the high importance of benzoquinone 3 as an intermediate in the synthesis of vitamin E, we report herein the MTO-catalysed selective oxidation of pseudocumene in the presence of different amphiphiles as an appealing alternative to the existing methods and to improve product selectivity of 3.
First, a number of commercially available neutral, anionic and cationic amphiphiles, shown in Fig. 1, were probed in the target oxidation of pseudocumene, at 50 °C, using MTO as a catalyst and hydrogen peroxide (30% aqueous solution) as an oxidant.† The results are summarised in Table 1. Side-products of the reaction are usually trimethylphenol, acting as an intermediate on the way to 3,26 or derivatives of 1 with oxidised methyl groups. These by-products were observed with GC/MS techniques. As it can be seen from Table 1, the use of certain amphiphiles can have a positive effect on the conversion of the reaction while maintaining a high selectivity. Indeed, the best results are obtained when using the inexpensive, neutral amphiphile Brij 30. When this additive is used in the presence of aqueous H2O2 solution as only solvent, the product selectivity is 67% (Table 1, entry 3). A reduction of the amount of amphiphile leads to a slightly increased conversion, but is accompanied by a significantly lower selectivity (Table 1, entry 3 vs. 4). Interestingly, the use of an additional solvent, such as nitromethane, affords a selectivity of 80%, which is the highest from all experiments with amphiphiles shown in this work (Table 1, entry 5). A water-miscible solvent such as methanol has no particular effect (Table 1, entry 3 vs. 6).
![]() | ||
Fig. 1 Amphiphilic additives used in this work. |
Entry | Reaction conditionsa | Time/h | Temp./°C | Conv. 1 [%] | Sel. 3 [%] |
---|---|---|---|---|---|
a Reaction conditions: 1 (1.44 mmol; 1 equiv.), MTO (2 mol%), H2O2 (30% in H2O, 4 equiv.), H2O2 (aq. solution)![]() ![]() ![]() ![]() |
|||||
1 | 20 | 50 | 13 | 100 | |
2 | Brij 30/without MTO | 20 | 50 | 0 | 0 |
3 | Brij 30 | 20 | 50 | 27 | 67 |
4b | Brij 30 | 20 | 50 | 38 | 47 |
5c | Brij 30, MeNO2 | 20 | 50 | 28 | 80 |
6c | Brij 30, MeOH | 20 | 50 | 31 | 52 |
7c | 4 mol% salox, Brij 30, MeNO2 | 22 | 50 | 29 | 72 |
8c | 2 mol% salox, Brij 30, MeNO2 | 72 | 50 | 39 | 62 |
9c | 2 mol% salox, Brij 30, H2O2 (50%), MeNO2 | 72 | 50 | 50 | 60 |
10d | 4 mol% salox, Brij 30, MeNO2 | 72 | 50 | 37 | 57 |
11e | 4 mol% salox, Brij 30, MeNO2 | 72 | 50 | 35 | 63 |
12 | 4 mol% (Bu4N)Br, Brij 30 | 22 | 50 | 21 | 0 |
13 | 4 mol% (Bu4N)PF6, Brij 30 | 19 | 50 | 28 | 46 |
14 | 4 mol% (Bu4N)HSO4, Brij 30 | 22 | 50 | 24 | 54 |
15e | 4 mol% salox, 10 mol% (Bu4N)HSO4, Brij 30, MeNO2 | 72 | 50 | 21 | 24 |
16 | 1 mol% CTAS | 72 | 50 | 36 | 44 |
17 | 50 mol% CTAT | 72 | 50 | 55 | 11 |
18c | 4 mol% N(Dodec)3, 2 mol% CTAT, CHCl3 | 72 | 40 | 30 | 27 |
19 | 2 mol% SDS | 72 | 40 | 31 | 55 |
We have shown that the use of salicylaldoxime as a ligand in combination with MTO improved the yield and selectivity of the oxidation of pseudocumene in comparison with the ligand-free analogue oxidation.26 Hence, salicylaldoxime was tested as a ligand for the target oxidation in the presence of Brij 30, yielding benzoquinone 3 with a selectivity of 72% (Table 1, entry 7). Interestingly, the amount of nitromethane added to the system seems to have two contrary effects reflected by different selectivities (Table 1, entries 7, 10, and 11).
Higher diluted systems (Table 1, entry 11) probably lack amphiphile/salox coordination to MTO, while too concentrated systems (Table 1, entry 10) lose the beneficial effect nitromethane seems to induce during the first oxidation step.26 In both cases, the selectivity is lower than in the medium diluted case (Table 1, entry 7). The addition of ammonium salts as phase transfer catalysts (PTC) to the Brij 30-containing reaction mixture does not improve the conversion or product yield. Nevertheless, the anion of a PTC seems to have an effect on the reaction. For instance, (Bu4N)Br inhibits the reaction, whereas (Bu4N)PF6, and (Bu4N)HSO4 afford selectivities of around 50% (Table 1, entries 12–14). Common cetyltrimethyl derived cationic amphiphiles lead to low selectivities (Table 1, entries 16–18), while anionic sodium dodecyl sulfate (SDS) affords moderate selectivity values (Table 1, entry 19). Generally, the use of ionic additives to the reaction lowers the selectivity significantly. Non-ionic amphiphile Brij 30 alone provides much better selectivities and the probing of similar amphiphiles appears reasonable. Amphiphiles could possibly be improved by additional functionalities like Lewis basic moieties. Such a combination might allow the combination of the positive effects of Lewis bases in MTO catalysed oxidations (higher catalyst stability and improved selectivity) and the positive effect of amphiphiles shown in this work. Amphiphile and Lewis base combined to one molecule could lead to a superior behaviour compared to adding the two separate substances to the reaction mixture (Table 1, entries 7–11 and 15).
Footnote |
† General procedure for the MTO-catalysed oxidation of 1 using amphiphiles: to a solution of MTO (2 mol%), 1 (1.4 mmol, 1 equiv.), the amphiphile of choice (see Table 1) and solvent (when indicated, see Table 1) H2O2 30% (4 equiv.) was added to start the reaction. The reaction mixture was stirred at 40–50 °C temperature for 20–72 h. After the reaction was stopped, the crude mixture was extracted with diethyl ether. Subsequently, a catalytic amount of MnO2 was added to destroy traces of peroxide if necessary, and the resulting solution was dried over anhydrous sodium sulfate, filtered and analysed by GC-MS using 4-methylbiphenyl and n-decane as internal standard. For characterisation, 2,3,5-trimethyl-1,4-benzoquinone (3), was purified through flash chromatography (dichloromethane/pentane 4![]() ![]() |
This journal is © The Royal Society of Chemistry 2012 |