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Ind. Eng. Chem. Res. 2011, 50, 1146–1149
Synthesis of Chalcones via Claisen-Schmidt Reaction Catalyzed by Sulfonic Acid-Functional Ionic Liquids Hua Qian* and Dabin Liu School of Chemical Engineering, Nanjing UniVersity of Science and Technology, Nanjing 210094, People’s Republic of China
Chunxu Lv Jiangsu Pharmaceutical Intermediate Research Center, Nanjing 210094, People’s Republic of China
Four recyclable sulfonic acid-functional ionic liquids (ILs) were prepared and used as dual catalyst and solvent for the synthesis of chalcones via Claisen-Schmidt condensation between acetophenone and benzaldehyde. All four ILs proved to be very active, leading to an 85%-94% yield of chalcone in the presence of 20% ILs. The chalcones can simply be separated from mixtures by simple decantation. After removal of the water, the ILs can be readily recovered and reused successfully without any significant loss of catalytic activity, which are potential substitutes for conventional homogeneous/heterogeneous acidic catalysts. 1. Introduction
2. Experimental Section
Chalcones and their derivatives are attracting increased attention, because of numerous pharmacological applications. They are the main precursors for the biosynthesis of flavonoids and exhibit various biological activities, such as anticancer, antiinflammatory, and antihyperglycemic agents.1-3 Traditionally, chalcones could be obtained via Claisen-Schmidt condensation carried out in acidic or basic media under homogeneous conditions, with many drawbacks, such as catalyst recovery and waste disposal problems.4 As a potential alternative, heterogeneous catalysts have also been used for Claisen-Schmidt condensation, including Lewis acids,5,6 Brønsted acids,7 solid acids,8-10 and solid bases.11-13 However, most of them still require expensive toxic solvents to facilitate the heat and mass transfer of the liquid phase in reaction systems. Because of particular properties, ionic liquids (ILs) have been emerged as a powerful alternative to conventional molecular organic solvents, and they are becoming a greener alternative to volatile organic solvents. Some common ILs have been tried in Claisen-Schmidt condensation, and they show a significant enhancement in the yield of chalcone.14-17 However, most of them are liposoluble, the products must be extracted with extra organic solvents, and ILs are difficult to recover.16 Furthermore, some ILs are poisonous, which are harmful for the environment.17 We are especially interested in developing the potential use of efficient and clean IL catalysts. Novel sulfonic acid-functional ILs are prepared through a simple and atomeconomic neutralization reaction. In comparison to imidazoliumbased ILs, the sulfonic acid-functional ILs have a relatively lower cost, lower toxicity, and higher catalytic activity.18 We tried a series of acid ILs in the nitration of DAPT (3,7-diacetyl1,3,5,7-tetraazacyclo-[3.3.1]-octane) to form the very powerful military explosive HMX (1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane), and we attained great success.19,20 In continuation of our work in studying acid-catalyzed reactions in ILs, we report an efficient and environmentally friendly solvent-free method for the synthesis of chalcone using sulfonic acid-functional ILs as dual catalyst and solvent, which is a potential substitute for conventional homogeneous/heterogeneous acidic catalysts.
2.1. Materials and Reagents. 1,4-Butanesultone and trifluoroacetic acid were of reagent grade and obtained from J&K Co., Ltd. All other chemicals were also obtained from commercial sources and were of reagent grade. Dichloromethane was dried over a 4 Å´ molecular sieve before use. 2.2. Synthesis of SO3H-Functional Ionic Liquids. In a typical experiment, a mixture of triethylamine (0.1 mol) and 1,4-butanesultone (0.1 mol) was charged into a 250-mL roundbottom flask. The reaction proceeded at 40 °C for 24 h and was vigorous stirred. After filtration, the solid product was washed with ethyl ether (3 × 10 mL) and dried under vacuum (70 °C, 0.1 MPa). Then, zwitterions (0.1 mol) were dissolved in 50 mL of deionized water, and 0.1 mol of acid (a mixture of nitric acid, sulfuric acid, 4-toluene, sulfonic acid, trifluoroacetic acid) was added dropwise with vigorously stirring and the reaction mixture stirred for an additional 6 h at 60 °C. Extra water was removed by rotary evaporation (70 °C, 0.1 MPa), and SO3H-functional ILs were obtained with a total yield of 68% (See Scheme 1). 2.3. Characterization of Ionic Liquids. The synthesized ILs were identified by 1H NMR and 13C NMR spectral data. Its relative acidity was determined using an ultraviolet-visible light (UV-vis) spectrophotometer, with 4-nitroaniline being used as an indicator. [TEBSA][NO3] 1H NMR (300 MHz, D2O). δ 1.03-1.08 (t, 9H, J ) 6.7 Hz), 1.60-1.63 (m, 2H), 2.74-2.78 (t, 2H, J ) 6.6 Hz), 2.98-3.11 (m, 8H). 13C NMR (75.5 MHz, D2O): δ 58.87, 54.23, 51.40, 23.07, 21.12, 7.11. Scheme 1. The Synthesis Process of [TEBSA][X] (X- ) NO3-, HSO4-, pTSO-, CF3COO-)
* To whom correspondence should be addressed. Tel./fax: +86 025 84314929. E-mail:
[email protected]. 10.1021/ie101790k 2011 American Chemical Society Published on Web 12/08/2010
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Scheme 2. Claisen-Schmidt Condensation Catalyzed by Ionic Liquids (ILs)
[TEBSA][HSO4] 1H NMR (300 MHz, D2O). δ 1.08-1.11 (m, 9H, J ) 7.2 Hz), 1.64 (t, 2H), 2.77-2.81 (t, 2H, J ) 7.2 Hz), 3.00-3.14 (m, 8H). 13C NMR (75.5 MHz, D2O): δ 56.38, 52.68, 50.17, 21.80, 19.84, 6.98. [TEBSA][CF3COO] 1H NMR (300 MHz, D2O). δ 1.03-1.07 (t, 9H, J ) 7.0 Hz), 1.61 (m, 4H), 2.74-2.79 (t, 2H, J ) 7.5 Hz), 2.97-3.10 (m, 8H). 13C NMR (75.5 MHz, D2O): δ 165.5, 117.4, 59.07, 54.83, 52.67, 24.15, 22.90, 7.86. [TEBSA][pTSO] 1H NMR (300 MHz, D2O). δ 1.05-1.08 (t, 9H, J ) 6.3 Hz), 1.64 (m, 4H), 2.23 (s, 3H), 2.80-2.82 (t, 2H, J ) 6.6 Hz), 3.01-3.11 (m, 8H), 7.19-7.22 (d, 2H, J ) 7.8 Hz), 7.51-7.54 (d, 2H, J ) 7.7 Hz). 13C NMR (75.5 MHz, D2O): δ 143.6, 142.4, 129.5, 124.1, 58.69, 52.01, 51.83, 22.48, 20.51, 18.57, 7.55. 2.4. Reaction Procedure. A mixture of benzaldehyde (20 mmol), acetophenone (20 mmol), and IL (4 mmol) was charged into a magnetically stirred three-necked round-bottom flask that was equipped with a condenser system. The mixture was heated to 120 °C and vigorously stirred under N2 atmosphere for 4-6 h. After the reaction was completed (TLC detected), the upper organic phase was separated from IL by decantation and chalcone was obtained. The dissolved organic species in IL could be extracted with ethyl acetate (3 × 5 mL), and the extractant was combined with the upper organic phase and then washed with a saturated solution of Na2CO3 (5 mL) and water (3 × 5 mL), dried over Na2SO4, and analyzed via gas chromatography (GC). IL was recovered from the aqueous solution by removing water at 70 °C under vacuum (0.1 MPa) for 5 h, and it was reused without a significant loss of its reactivity (See Scheme 2). 3. Results and Discussion The measurement of the Brønsted acidic scale of these SO3H-functional ILs was conducted on a Model UV-240 spectrophotometer with a basic indicator, according to the literature previously reported.21 With the addition of acidic ILs, the absorbance of the unprotonated form of the basic indicator decreased, so the [I]/[IH+] ratio could be calculated from the measured absorbance differences, and then the Hammett function, H0, is calculated using eq 1: H0 ) pK(I)aq + log
( ) [I] [IH+]
(1)
where pK(I)aq is the pKa value of 4-nitroaniline (pK(I)aq ) 0.99), and [I] and [IH+] are, respectively, the molar concentrations of the unprotonated and protonated forms of 4-nitroaniline. This value can be regarded as the relative acidity of the ILs. The results of acidities of four ILs are shown in Figure 1. The maximal absorbance of the unprotonated form of 4-nitroaniline was observed at 350 nm in CH2Cl2 (see spectra a in Figure 1). We could determine the [I]/[IH+] ratio by measuring the absorbance when each IL was added (see spectra b-e in
Figure 1. Absorption spectra of 4-nitroaniline in various ionic liquids (ILs) in dichloromethane. Table 1. Hammett Function (H0) Values of Ionic Liquids (ILs) in Dichloromethane at Room Temperature ionic liquid
absorbance
[I] (%)
[IH+] (%)
Hammett function, H0
blank [TEBSA][pTSO] [TEBSA][CF3COO] [TEBSA][NO3] [TEBSA][HSO4]
1.025 0.871 0.782 0.568 0.323
100.0 73.6 68.1 52.8 19.9
0 26.4 31.9 47.2 80.1
1.44 1.32 1.03 0.38
Table 2. Claisen-Schmidt Condensation Catalyzed by Different SO3H-Functional Ionic Liquids (ILs)a entry
ionic liquid
yield (%)b
1 2 3 4 5
none [TEBSA][pTSO] [TEBSA][CF3COO] [TEBSA][NO3] [TEBSA][HSO4]
[TEBSA][NO3] > [TEBSA][CF3COO] > [TEBSA][pTSO] It is clear that the acidity of the ILs is dependent on the nature of anion, which will effectively affect their catalytic activities. For the beginning of this study, benzaldehyde and acetone were employed to compare the catalytic performance of different SO3H-functional ILs. As shown in Table 2,
