Short communication
PEG1000-DAIL / Toluene Temperature-dependent Biphasic System that Regulate Homogeneously Catalyzed Oxidation of Primary Alcohols to Carboxylic Acids
Yu Lin Hu,1 Xiao Yun Ma,2 Qiang Ge1 and Ming Lu1*
1 Chemical Engineering College, Nanjing University of Science and Technology, Nanjing 210094, PR China
2 Nanjing Simcere Pharmaceutical Co., Ltd, Nanjing 210042, PR China
* Corresponding author: E-mail: luming1963@163.com Tel: 86-025-84315030, Fax: 86-025-84315030
Received: 28-02-2010
Abstract
An efficient and convenient procedure for the hydrogen peroxide oxidation of primary alcohols to the carboxylic acids in aqueous media in regulated temperature-dependant; recyclable phase-separation catalytic system comprised of the PEG1000-based dicationic acidic ionic liquid and toluene under homogeneous conditions in good to excellent yield is reported.
Keywords: Primary alcohols, oxidation, carboxylic acids, PEG1000-DAIL, thermo-regulated ionic liquid biphasic system.
1. Introduction
Carboxylic acids are important classes of chemicals used extensively for the preparation of a variety of fine or special chemicals such as polymers, pharmaceuticals, solvents, and food additives,1 and versatile methods for the preparation of these type of compounds have been reported. However, direct conversion of primary alcohols to the corresponding carboxylic acids is still a challenge especially in the presence of other functional groups. There are few reports for this oxidation of primary alcohols to the corresponding carboxylic acids including CrO3/H2SO4,2,3 TEMPO/NaClO,45 RuCl3/H5IO6,6 CrO3/H5IO6,7 and Co(II)/H2O2.8 However, these procedures are invariably associated with one or more disadvantages such as long reaction time, high temperature, low yields, difficulties in work up, and unpleasant to the environment. Consequently, there is a great need to develop new and environmentally benign procedures that address these drawbacks in oxidation protocols.
Ionic liquids (ILs) have gained recognition as possible environmentally benign solvents because of their favorable properties such as negligible volatility and non-flammability under ambient conditions, large liquid ran-
ge, high thermal stability, wide electrochemical window, and strong ability to dissolve many chemicals.9 Therefore, ILs have found wide applications in chemical synthe-sis,10-12 biocatalytic transformations,13 electrochemistry,14 and analytical and separation science.15 In view of both the advantages and disadvantages of homogeneous and heterogeneous catalysts, and to improve catalyst recovery, multiphase systems, such as phase-transfer catalysis,16,17 thermo-regulated phase-transfer catalysis,18 and liquid-liquid biphasic catalysis,19 have been studied. Some novel temperature-dependent ionic liquid biphasic catalytic systems have been reported recently.20-22 Luo and co-workers reported very recently a new PEG1000-based dicationic ionic liquid exhibiting temperature-dependent phase behavior with toluene and had successfully applied it in one-pot synthesis of benzopyrans.23 They found that the IL showed some advantages such as high conversions and selectivity, stability at high temperatures, and reusability, which provide a novel route for the separating and recycling of the catalysts. Based on the concept of thermo-regu-lated ionic liquid biphasic system (TRILC) and from Luo's good experiences in the application of the IL, we now report an efficient and convenient procedure for the oxidation of primary alcohols to the corresponding car-
boxylic acids with H2O2, catalyzed by the PEG1000-based dicationic acidic ionic liquid (PEG1000-DAIL) in aqueous media (Scheme 1). We found that the PEG1000-DAIL/to-luene temperature-dependent biphasic system is active and an environmentally acceptable catalytic system for oxidation of alcohols.
Table 1. Optimization of the reaction conditions for oxidation of 4-methylbenzyl alcohol to 4-methylbenzoic acida
Scheme 1
2. Results and Discussion
The initial study was carried out using 4-methyl-benzyl alcohol as the substrate to optimize the reaction conditions, and the results are summarized in Table 1. At first, the oxidation was tested with H2O2 as the oxidant in the presence and absence of PEG1000-DAIL catalytic system. In the absence of PEG1000-DAIL, the reaction proceeded very slowly and the yield was only 26% after 24 hours (Table 1, entry 1). When the reaction was catalyzed with only 0.02 equivalents of PEG1000-DAIL, the yield increased to 57% in 8 hours (Table 1, entry 2). The yield was improved with increasing the amount of PEG1000-DAIL (Table 1, entries 2-5), and reached maximum with 0.1 equivalents of PEG1000-DAIL (Table 1, entry 5). Further increasing of the equivalent of PEG1000-DAIL, under the same conditions, did not significantly enhance the yield (Table 1, entry 6). These experiments revealed that 0.1 equivalents of the catalyst were necessary to complete the reaction in 4 hours.
The catalytic system could be recovered and reused for subsequent reactions with no appreciable decrease in yields and reaction rates (Figure 1). The recycling process involved the removal of the upper oil layer containing toluene and product by decantation, and concentration of the aqueous layer containing the catalytic system by removing the water through a water knockout drum. Fresh substrate and toluene were then recharged to the residual PEG1000-DAIL and the mixture was heated to react once again. Only 6% loss of weight was observed after 8-times recycling.
Various benzylic and allylic alcohols can be successfully oxidized by this oxidation system to the corresponding carboxylic acids in good to high yields (Table 2, entries 1-10). However, aliphatic primary alcohol 2-phenylethanol was found inert in this oxidation reaction, and even under more drastic reaction conditions, no pro-
Entry	Ionic	Ionic liquid	Time	Yield
	liquid	(equiv.)	(h)	(%)b
1	PEG1000-DAIL	-	24	26
2	PEGiooo-DAIL	0.02	8	57
3	PEG1000-DAIL	0.07	6	84
4	PEG1000-DAIL	0.09	4	91
5	PEG1000-DAIL	0.10	4	96
6	PEG1000-DAIL	0.11	4	96
a Reaction conditions: 4-methylbenzyl alcohol (10 mmol), H2O2 (50%, 12 mL), toluene (12 mL), 85 °C. b Isolated yield.
duct was detected (Table 2, entry 12). The substituent's on the aromatic ring have influence on the oxidation rate, i.e., benzylic alcohols having electron-donating groups on the aromatic ring (Table 2, entries 2-6 and 8) are more reactive than those having electron-withdrawing groups (Table 2, entry 11).
Fig. 1. Repeating reaction cycles using recovered PEG1000-DAIL catalytic ystem.
The proposed catalytic oxidation of alcohols with H2O2 in PEG1000-DAIL / toluene system is schematically presented in Figure 2. Before the oxidation, there is an oil-water biphasic system, and the bottom layer (aqueous phase) consists of PEG1000-DAIL and hydrogen peroxide. PEG1000-DAIL catalytic system is completely dissolved in aqueous phase, and the upper layer (oil phase) consists of toluene and primary 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 next step involved the removal of the upper toluene layer, containing product, by decantation and concentration of the bottom layer with the catalytic system by removing the water through a water knockout drum. Fresh substrate and toluene were then recharged to the residual PEG1000-DAIL and recycled. The PEG1000-DAIL catalytic system has a crucial role in the oxidation process to locally concentrate the reacting spe-
Table 2. Oxidation of primary alcohols to carboxylic acidsa
Entry Substrate
10
11
12
Product
ch2oh
cooh
k
ch2oh
cooh
Í1 , ch3 2
ch2oh	cooh
och3	och3 j
ch2oh
T
cooh HqC.	.CH-)
ch2oh	cooh
Ä A
och3	och3 5
O /wCH2OH	„	r
<»jo ca
cooh
7
CH20H	cooh
§ £
c(ch3)3	c(ch3)3 8
10
11
Time Yield
(h) (%)c
24
24
92
96
97
98
99
95
94
93
93
90
45d
a Reaction conditions: alcohol (10 mmol), H2O2 (50%, 12 mL), toluene (12 mL), PEG1000-DAIL (1 mmol), 85 2C. b All products are known compounds and were identified by comparing their HPLC spectra with those of commercially available materials. c Isolated yield. d 50% of starting material was recovered. e No product was detected.
cies by exhibiting a temperature-dependent phase behavior with toluene. Namely, the thermo-regulated biphasic behavior of mono-phase at high temperature and bi-phase at room temperature leads to a large increase in the effective reactant concentration and the excellent reaction yields. The yields of products obtained by this catalytic system could be remarkably improved by 10-20% in contrast to the synthetic methods reported previously.2-8
Room temperature
Reaction temperature
Room temperature
RCHjOH		Homogeneous		RCOOH
Toluene	Heating -N	Oxidation	Cooling	Toluene
PEG1M0-DAIL Cat.				PEQ^j-DAIL
50%H202		v \ RCOOH		Cat.
*	Catalyst Recycling			I
Figure 2. Thermo-regulated ionic liquid biphase catalytic oxida-				
tion process.				
	3. Conclusions			
We have developed a simple and efficient procedure				
for the H2O2 oxidation of primary alcohols to carboxylic acids in the PEG1000-DAIL / toluene temperature-dependent biphasic system. Mild reaction conditions, easy wor-kup and isolation of products, high yields, stability, good thermo-regulated biphasic behavior of the ionic liquid, and excellent recyclability of the catalyst are the attractive features of this methodology. Further aspects of this catalytic system and the application to other organic systems are under investigation.
4. Experimental
All chemicals were from commercial sources and used without any pretreatment, and reagents were of analytical grade. The ionic liquids were synthesized according to the literature procedures.23 High performance liquid chromatography (HPLC) analyses were performed on a Dionex Softron GmbH (America) system, consisting of a pump (P680), UV-vis detector system (170U), and Diacovery C18 column (4.6 x 250 mm). NMR spectra were recorded on a Bruker 400-MHz spectrometer using CDCl3 as the solvent with tetramethylsilane (TMS) as an internal standard. Elemental analyses were performed on a Vario EL III instrument (Elmentar Anlalysensy Teme GmbH, Germany).
General procedure for the oxidation of primary alcohols. To a stirred solution of alcohol (10 mmol) in ionic liquid PEG1000-DAIL (1 mmol) and toluene (12 mL) was added H2O2 (50%, 12 mL) at room temperature and stirring was continued at 85 °C for the appropriate time (see Table 2). The reaction progress was monitored by HPLC.
1
4
6
9
5
e
0
After completion of the reaction, the reaction mixture was cooled to the room temperature and the organic phase separated by decantation, and rinsed with water (3 x 10 mL). The organic phase was dried with sodium sulfate, filtered, and the solvent removed under reduced pressure. The residue was passed through silica gel pad to afford the pure product. All further runs were performed under identical reaction conditions. Spectroscopic data for selected products are as follows.
2,4,6-trimethylbenzoic acid (4). 1H NMR (400MHz, CDCl3): 5 2.24 (s, CH3, 3H), 2.49 (s, CH3, 6H), 7.28 (s, Ar-H, 2H), 11.5-12.9 (broad, COOH, 1H ). 13C NMR (400MHz, CDC13): 5 21.2, 22.5, 125.8, 129.4, 131.3, 140.9, 168.5. Anal. Calcd. for C10H12O2: C, 73.15; H, 7.37; O, 19.49. Found: C, 73.11; H, 7.38; O, 19.50. 3,4,5-trimethoxybenzoic acid (5). 1H NMR (400MHz, CDCl3): 5 3.79 (s, CH3O, 3H), 3.94 (s, CH3O, 6H), 7.18 (s, Ar-H, 2H), 11.7-13.1 (broad, COOH, 1H ). 13C NMR (400MHz, CDC13): 5 52.6, 58.4, 104.5, 124.2, 141.7,
151.4,	169.1. Anal. Calcd. for C10H12O5: C, 56.60; H, 5.70; O, 37.70. Found: C, 56.57; H, 5.770; O, 37.72. 3,4-(Methylenedioxy)-benzoic acid (6). 1H NMR (400MHz, CDCl3): 5 6.06 (s, CH2, 2H), 7.18-7.57 (m, Ar-H, 3H), 11.4-13.2 (broad, COOH, 1H ). 13C NMR (400MHz, CDC13): 5 97.8, 102.7, 109.5, 121.4, 122.8,
143.5,	150.4, 168.7. Anal. Calcd. for C8H6O4: C, 57.84; H, 3.64; O, 38.52. Found: C, 57.79; H, 3.(56; O, 38.53. Cinnamic acid (9). 1H NMR (400MHz, CDCl3): 5 6.10 (d, CH, 1H), 7.14 (d, CH, 1H), 7.28-7.56 (m, Ar-H, 5H), 11.6-13.0 (broad, COOH, 1H ). 13C NMR (400MHz, CDC13): 5 112.8, 126.5, 127.4, 128.2, 131.7, 139.6, 169.8. Anal. Calcd. for C9H8O2: C, 72.97; H, 5.43; O, 21.57. Found: C, 72.96; H, 5.44; O, 21.60.
5. Acknowledgement
We thank the National Basic Research Program (973) of China (No. 613740101) and Natural Science Foundation of Jiangsu Province for support of this research. The authors would also like to express their thanks to Prof. Luo for experimental assistance.
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Povzetek
Avtorji v prispevku poročajo o učinkoviti in enostavni oksidaciji primarnih alkoholov z vodikovim peroksidomdo kar-boksilnih kislin v reguliranem sistemu s temperaturno odvisno fazno separacijo. Oksidacija poteka pod pogoji homogene katalize s PEG1000-dikationsko kislo ionsko tekočino in toluenom v vodnem mediju z zelo dobrimi izkoristki.