Oxidation of alcohols with hydrogen peroxide in the presence of a new triple-site phosphotungstate

A new clean catalytic process for the selective oxidation of alcohol to ketones has been studied. The catalytic properties were investigated with aqueous hydrogen peroxide under halide-and organic solvent-free conditions. The results show that triethyl({2,4,6-trimethyl-3,5-bis[(triethylazaniumyl)methyl]phenyl}methyl)azanium (tribromide) based phosphotungstate complex (TBAP) has excellent catalytic ability to the oxidation reaction of alcohol by hydrogen peroxide with high yield. Moreover this catalyst could be easily recovered by simple workup and reused up without any appreciable loss of its activity.


Introduction
The selective aqueous biphasic catalytic oxidation of alcohols to the corresponding carbonyl compounds is of significant importance in the fine chemicals and pharmaceutical industries.Oxidations can be carried out with many different oxidants.Commonly, traditional alcohol oxidation employs the strongest stoichiometric oxidizing agents, such as PCC, PDC, KMnO4, MnO2, Na2Cr2O7, TEMPO, CrO3 and so on. 1,7These oxidation operations are quite useful in lab, but these oxidants are expensive, hazardous or toxic.Meanwhile toxic solvents are usually used to dissolve oxidizing agents and a large amount of inorganic wastes are produced after workup.Hence, in terms of economical and environment concern, catalytic oxidation processes with inexpensive and environmental-friendly oxidants are extremely valuable.
Multi-site phase transfer catalysts (MPTCs) containing more than one catalytic active site in a molecule were one of unique class.This type of MPTCs offers the potential of providing great PTC activity and accelerating the particular synthetic transformation even under mild conditions.
Here, we reported a very facile and practical oxidation of alcohols with H2O2 in presence of TBAP, developed under mild conditions and affording products with high yields in short time (Scheme 1).The major advantage of this method apart from solvent-free conditions is that triple-site phase-transfer catalysis can be prepared easily without using toxic reagents and could be used for the next cycle.
TBAP Scheme 1. Oxidation of alcohols with hydrogen peroxide catalyzed by TBAP.

Results and Discussion
In order to search for an optimum reaction conditions, cyclohexanol is choosed as a model substance.The reaction was carried out with a molar ratio cyclohexanol / TBAP / 30% H2O2 1: 0.001: 1 at 90 o C. Cyclohexanol was oxidized to cyclohexanone in 40% yield.After some experimentation with respect to the molar ratio of catalyst, we found that the use of 0.005 molar TBAP per mole of the substrate in water consistently produced good yields of cyclohexanone (70%).However, further increasing the amount of catalyst under the same conditions did not enhance the formation of the cyclohexanone significantly.A blank experiment was also carried out which revealed that in the absence of the TBAP, less than 8% yield of cyclohexanone was detected.
Having established the importance of the PTC, we switched our attention to the amount of hydrogen peroxide.The excess amount of hydrogen peroxide required is a result of its decomposition at the elevated temperature.The oxygen released in the decomposition reaction plays no role in the oxidation of alcohols.No oxidation occurred under similar conditions but using oxygen as oxidant.Thus, we investigated the oxidation with different amounts of 30% H2O2 in order to improve the yield.It was obvious that yield was increased from 70% to 92% with the 1.5 molar ratio amount of hydrogen peroxide added.However, further addition the amount of 30% H2O2 under the same conditions, the yield was not increased significantly.The optimal molar ratio 30% H2O2/substrate is 1.5.

Catalytic oxidation process
The proposed catalytic oxidation of alcohols with H2O2 in presence of TBAP is schematically presented in Figure 2. The solubility of TBAP in water was affected with temperature change.Before the oxidation, there is an oil-water triphasic system, and the bottom layer (aqueous phase) consists of TBAP and hydrogen peroxide.TBAP is completely suspended in aqueous phase, and the upper layer (oil phase) was alcohol.During the oxidation, the oil-water layer disappears and a homogeneous reaction medium is formed.After the completion of the reaction, a complete phase-separation occurred again, after cooling to the room temperature.The TBAP catalytic system has a crucial role in the oxidation process by exhibiting an emulsion dispersion phase behavior.Namely, the emulsion dispersion phase behavior of homogenous phase at high temperature and precipitation at room temperature leads to a large increase in the number of catalytic reactive sites and the excellent reaction yields.

Heating Cooling
Room temperature Reaction temperature Room temperature

Catalyst Recycling
Emulsion dispersion Oxidation Cat.

Figure 2. TBAP emulsion dispersion catalytic oxidation process.
From the above research results, the reaction condition was optimized and extended to other primary and secondary alcohols.These results are shown in Table 1. a Reaction conditions: 5 mmol catalyst; 1 mol substrate; 1.5 mol 30%aq.H2O2; reaction time 2 h.b All products are known compounds and were identified by comparing their GLC spectra with those of commercially available materials.c Isolated yield.d Toluene as solvent.e. 5% H2O2 was used.
Table 1 showed representative results for oxidation of aliphatic alcohol and aromatic alcohol to corresponding carbonyl compounds.The aliphatic primary alcohol was difficult to be effectively oxidized to corresponding aldehyde or carboxylic acid and its conversion was very low (entry 10).However, the secondary alcohols were oxidized to ketones in high yield.It was active for oxidation of benzyl alcohol due to the active phenyl group.

Catalyst reusability
Reusability was initially studied for the oxidation of cyclohexanol as that would give us an insight whether the triple-site active catalyst was available for the second step of oxidation.The results illustrated in Figure 3 showed that the fresh and recycled catalyst had high activities in all runs without any appreciable loss of its activity.

Conclusions
In summary, we have developed an emulsion dispersion TBAP catalytic system for oxidation of alcohols in water with hydrogen peroxide to corresponding carbonyl compounds in high conversion under halide-and organic solvent-free conditions.The catalytic reactions were quite selective with high yield for oxidations of benzylic and secondary alcohols.The catalyst exhibits high activities in all runs without any appreciable loss of its activity, which is an environmentally

1, 3,5-tri-(Bromomethyl)-2,4,6-trimethylbenzene.
To mesitylene (44.5 g, 0.37 mol) and p-formaldehyde (36.6 g, 1.22 mol) was added glacial acetic acid (185 mL) and hydrobromic acid (33% in acetic acid, 260 mL).The suspension was stirred under nitrogen atmosphere and heated at 95 o C.After 24 h the reaction mixture was crashed into ice water (150 g) and stirred vigorously.The formed precipitate was filtered off, washed with water and recrystallized from dichloroethane to give the title product as a white power.Yield: 80%; M.P.: 187-188 o C 1 H NMR (500 MHz, CDCl3): σ 2.46 (s, 9H, Ar-CH3), 4.57(s, 6H, -CH2); 13  The title compound was prepared following the previous literature reported. 251, 3, 5-Tris ( bromomethyl )-2, 4, 6-trimethylbenzene (4 g, 11.8 mmol) was dissolved in dry acetonitrile (10 mL) and transferred into a 150 mL three-necked round-bottomed flask.Triethylamine (4.17 g, 41.29 mmol) dissolved in acetonitrile (15 mL) was added to the solution.The reaction mixture was stirred vigorously under inert atmosphere (N2).The reaction was refluxed for 24 h.After completion of the reaction, the mixture was cooled to room temperature to obtain the pale yellowish solid.Yield: 85%; 1 H NMR (500 MHz, DMSO): σ 1.08-1.29 (m, 27H, -CH3), 2.65 (s, 9H, Ar-CH3), 3.29-3.35(m, 18H, -CH2), 4.81 (s, 6H, -CH2).Synthesis of catalyst TBAP ( phosphotungstate complex ).The catalyst was prepared following the previous literature reported. 26Tungstic acid (5 g, 20 mmol) was added portion wise to a 30% solution of H2O2 (20 mL) with stirring and heated to 60 o C, and the mixture was stirred for 1 h until a colorless solution was obtained.H3PO4 (0.62 mL of 80% sol., calc.5 mmol) was added to the solution at room temperature and the whole was diluted to 60 mL with water.TBAT (2.34 g, 3.3 mmol) in CH2Cl2 (60 mL) was added dropwise to the above solution.A brownish yellow solid was precipitated with stirring.Filtered and washed with purified water to obtain the phosphotungstate complex solid.Yield: 95%.IR (neat, KBr plates) the absorption in the region 1106 and 1085 were assigned to P-O stretching vibration.A strong peak at 965 indicated the presence of W=O, and peaks at 885 (O-O).572 and 489 confirmed the tungstate structure.Absorption at 1636, 1475, 1456 and 1397 is due to phenyl ring (see Figure 4).General procedure of catalytic oxidation experiments.A 500 mL, round-bottomed flask equipped with mechanical agitation and a reflux condenser was charged with 8.06 g (5 mmol) of catalyst TBAP, 1 mol of each substrate and 169 g (1.5 mol) of aqueous 30% H2O2 were added successively.Then, the mixture was heated to 90 o C. H2O2 was consumed completely via an inspection with potassium iodide-starch test paper.The conversion of the substrate was monitored by GLC.After a suitable time interval the reaction was stopped and the product was separated, washed with saturated aqueous Na2S2O3 and distilled through a short column under vacuum.After separation of product, the aqueous layer was evaporated under vacuum or filtered by filtration membrane to obtain the catalyst.Readdition of alcohols (1 mmol) and 30% H2O2 to flask containing the TBAP was carried out for the next oxidation cycle.25, 128.51, 134.10, 137.11, 198.12.

Table 1 .
Oxidation of alcohols to carbonyl compounds a