An Efficient Synthesis of Bis-indolylindane-1,3-diones, Indan-1,3-diones, and Indene-1,3(2H)-denies Using [Hbim]BF4 Ionic Medium

We prepared a brand new molecule in one step for the synthesis of bis-indolylindane-1,3-dione and indan-1,3-diones from the reaction of ninhydrin and 3 substituted/unsubstituted indoles using [Hbim]BF4 ionic liquid in excellent yields. The method was also used for the synthesis of novel indene-1,3(2H)-denies derivatives.


Introduction
In recent times, ionic liquids have gained recognition as possible environmentally benign alternatives to the more volatile organic solvents [1]. Ionic liquids possess many attractive properties, such as wide liquid range, negligible vapor pressure, ease of recyclability, high thermal stability, and good solvating ability in a wide range of substrates and catalysts, which alleviate some of the environmental issues. Their nonvolatile nature can reduce the emission of organic compounds and facilitate the separation of products and/or catalysts from the reaction solvents. Furthermore, ionic liquids are found to be an efficient reaction medium for the immobilization of transition metal-based catalysts, Lewis acids, and enzymes [2]. The hallmark of such ionic liquids is the ability to alter their properties as desired by manipulating their structure with respect to the choice of organic cation or anion and side chain attached to the organic cation. Important pharmaceuticals often possess heterocyclic moieties as their building blocks [3]. The extensive use of heterocyclic compounds in the pharmaceutical industry is perhaps attributable to the availability of ample range of reactions that facilitate subtle structural modifications in heterocyclic compounds [4][5][6][7]. Since indole and its derivatives possess various biological activities [8], development of new methodologies for the synthesis of indole derivatives, which will yield subsets of heterocycles having potentiality to serve as templates for new biologically active molecules, is of great importance.

Experimental
2.1. General. All reagents were purchased from Merck and Aldrich and used without further purification. The ionic liquid, [Hbim][BF] 4 , was synthesized by the method reported in [9]. Melting points were determined using a Linkman HF591 heating stage, used in conjunction with a TC92 controller, and reuncorrected. NMR spectra were recorded using a Bruker DRX500 machine at room temperature. 1 H and 13 C NMR spectra were measured using deuterochloroform as solvent, 2 ISRN Organic Chemistry and chemical shifts were measured relatively to residual solvent or CFCl 3 as an internal standard for 19 F NMR and are expressed in parts per million ( ). Mass spectra were obtained using a Micro Mass LCT machine in ES or EI mode. Infrared spectra were measured on a Perkin Elmer Paragon 100 FT-IR spectrometer. Analytical thin layer chromatography (TLC) for monitoring reactions was performed using Merck 0.2 mm silica gel 60 f-254 Al-plates. [2,3 ]biindolyl-2 -ylidene)-indan-1,3-diones, Indene-1,3(2H)-denies, and 2,2-Bis(4-(dimethylamino)phenyl)-1H-indene-1,3(2H)-diones. 1 mmol ninhydrin (1) and 2 mmol indole derivatives 2(a-e) (for the synthesis 3(a-e)), 1 mmol ninhydrin (1) 1 mmol 1,2-phenylenediamine derivatives 4(a-c), and 2 mmol indole derivatives 2(a-d) (for the synthesis 6aa-6ae, 6ba-6be, 6ca-6ce) or 1 mmol ninhydrin (1), 2 mmol N,N-dimethylaniline 7(a-c) (for the synthesis 8(a-c)) were added to a 20 mL round bottom flask containing 2 mL [Hbim]BF 4 . The mixture was stirred at room temperature 25 ∘ C for appropriate time (monitored by TLC). After completion of the reaction, the reaction mixture was added with 5 mL water (IL is soluble in water). The precipitate was collected by filtration and purified by crystallization from chloroform/methanol to afford pure products. The filtrate was concentrated under reduced pressure and dried at 100 ∘ C to recover the ionic liquid for subsequent use.

General Procedure for the Synthesis of Bis
Spectroscopic data of new products are given below.     Table 2    a Yield refers to pure products after crystallization.   (Table 2 (Table 2 (Table 3 (Table 3
Next, I attempted to synthesize novel indene-1,3(2H)denies reaction of ninhydrin (1) with 1,2-phenylenediamine 4(a-c) and indole 2(a-e) derivatives under the same reaction condition (Scheme 1). Interestingly, a variety of indoles including N-1, C-2, and C-6 substituted indoles participated well in this reaction and gave the corresponding products in excellent yield. As seen, indoles carrying electron-donating substituent act well in this reaction conditions ( Table 2, entries 6-15).
We also investigated the recycling of the ionic liquid [Hbim]BF 4 under solvent free conditions. The reusability of IL was tested using a model reaction of ninhydrin and insole, 4,5-dimethylbenzene-1,2-domain and 2-methyl-1Hindole, and N,N-dimethylaniline as substrates for preparation of 3aa, 5bd, and 7a, respectively. After completion of the reaction, the reaction mixture was filtered to isolate the desired IL which was washed with ethyl acetate in order to remove the impurities and unreacted substrates and used for the next run. It was observed that there was no any substantial loss of catalytic activity even after the fifth run as indicated in Figure 1. The greenness of the protocols can be easily proven using the concept atom economy. Thus, we investigated the atom economy for each derivative synthesized and listed the values in Tables 1, 2
(vi) Relatively less toxic and biodegradable ionic liquid.