An Efﬁcient Synthesis of 1-Aryl-3-(indole-3-yl)-3-(2-aryl-1,2,3-triazol-4-yl)propan-1-one Catalyzed by a Brønsted Acid Ionic Liquid

An efficient synthesis of novel 1-aryl-3-(indole-3-yl)-3-(2-aryl-1,2,3-triazol-4-yl)propan-1-ones from indoles and 1-aryl-3-(2-aryl-1,2,3-triazol-4-yl)propan-1-one using a Brønsted acid ionic liquid [Sbmim][HSO4] as catalyst is described. Satisfactory results with excellent yields and short reaction time were obtained in the experiments. The catalyst could be recovered conveniently and reused efficiently.


Introduction
In recent years, β-indolylketones have received much attention because they represent an important substructure in both biologically active compounds and natural products [1]. A simple and direct approach for their synthesis involves the conjugate addition of indole and α,β-unsaturated ketones in the presence of either protic or Lewis acids. During the last decade, several improved methods have been reported for the preparation of these compounds using various catalysts such as FAP [2], I 2 [3], Zn-HAP [4], CAN [5], InBr 3 [6], PTSA [7], Bi(NO 3 ) 3 [8], HfCl 4 and ScCl 3 [9], PVSA [10], pyrrolidine and HClO 4 [11], GaI 3 [12], Zr(OTf) 4 [13], Bi(OTf) 3 [14] and so on. However, several of these reported OPEN ACCESS procedures suffer from the drawbacks such as strong acidic conditions, long reaction times, complex handling and low yields of products. Hence, new efficient and green procedures are still in strong demand. Recently, ionic liquids (ILs) have been widely used as environmentally benign reaction media in organic synthesis owing to their unique properties of nonvolatility, nonflammability, and recyclability [15,16]. In particular, the synthesis of task-specific ILs with special functions according to the requirements of a specific reaction has become an attractive field [17,18]. Recently, Yang et al. [19] reported the use of the Brønsted acid ionic liquid [Sbmim] [HSO 4 ] as catalyst for the hydrolysis of soybean isoflavone glycosides. In this process [Sbmim] [HSO 4 ] has good catalytic activities which are similar to those of sulfuric acid, giving a conversion of glycitin of more than 90%.

Results and Discussion
Initially, to evaluate the effect of the catalyst [Sbmim] [HSO 4 ] under different reaction conditions, the reaction of indole and 1-phenyl-3-(2-phenyl-1,2,3-triazol-4-yl)propan-1-one was selected as a model reaction. The results were presented in Table 1. It was clear that the best solvent was acetonitrile and the best molar ratio of IL/substrate is 10% (Table 1, entry 3). The influence of the reaction time on the yield was also investigated as shown in Table 1, entries 3, 8-12. It was found that a higher yield occurred when the reaction time was 3 h ( Table 1, entry 11), although, the yield did not change significantly when the reaction time was increased from 1 h to 5 h. For the purpose of saving energy, we chose 1 h as the reaction time. Hence, the best conditions employed a 0.1:1:1 mole ratio of [Sbmim][HSO 4 ], indole and 1-phenyl-3-(2-phenyl-1,2,3-triazol-4-yl)propan-1-one at 80 °C for 1 h using acetonitrile as solvent.
The recycling performance of TSIL [Sbmim] [HSO 4 ] was also investigated in the reaction of indole and 1-phenyl-3-(2-phenyl-1,2,3-triazol-4-yl)propan-1-one. After the separation of product, the filtrate containing catalyst was distilled under vacuum to remove water and the resulting catalyst was reused directly for the next run.  4 ] can be recycled at least three times without any significant decrease in catalytic activity, the yields ranged from 95% to 90% (entry 9 c ). This indicated that the ionic liquid [Sbmim] [HSO 4 ] was an efficient and recyclable catalyst for the reaction. In order to check the generality of the procedure, a variety of substituted indoles were reacted with 1-aryl-3-(2-aryl-1,2,3-triazol-4-yl)propan-1-one. In general, the reaction proceeded easily under the optimum conditions described above and the adducts were isolated in excellent yields ( Table 2).  4 ]-catalyzed synthesis of 1-aryl-3-(indole-3-yl)-3-(2-aryl-1,2,3triazol-4-yl)propan-1-one.  The results obtained indicated that the electron donating or withdrawing groups at the indole ring did not seem to affect the reaction significantly in terms of yields. As environmental consciousness in chemical research and industry has increased, the challenge for a sustainable environment has called for clean procedures that can avoid the use of organic solvents. Hence, we also examined the reaction of indoles and 1-aryl-3-(2-aryl-1,2,3-triazol-4-yl)propan-1-one under solvent-free condition, and the products were obtained in excellent yields (Table 2).
A proposed reaction mechanism for the conjugate addition of indole to 1-phenyl-3-

General
All compounds were characterized by IR, 1 H-NMR spectra and elemental analysis. The IR spectra were obtained as potassium bromide pellets with a FTS-40 spectrometer (BIO-RAD, U.S.A). The 1 H-NMR spectra were obtained on a Varian Inova-400 spectrometer using CDCl 3 or DMSO-d 6 as solvent (as indicated under each entry below) and TMS as an internal standard, chemical shifts are given in ppm. Elemental analyses (C, H, N) were performed on a Perkin-Elmer Analyzer 2400. Melting points were determined using a Büchi B-540 instrument. All melting points are uncorrected. The Brønsted acid ionic liquid [Sbmim] [HSO 4 ] was synthesized according to a previous literature method [19]. 1aryl-3-(2-aryl-1,2,3-triazol-4-yl)propan-1-one (2) was synthesized according to a previous literature report [21].