ISRN Organic Chemistry

Volume 2013 (2013), Article ID 528329, 8 pages

http://dx.doi.org/10.1155/2013/528329

Research Article

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

Mohammad Reza Poor Heravi

Department of Chemistry, Payame Noor University, P.O. Box 19395-3697, Tehran, Iran

Received 2 October 2013; Accepted 14 November 2013

Academic Editors: F. D'Anna, D.-M. Du, Y. Génisson, R. Pohl, and J. Wu

Copyright © 2013 Mohammad Reza Poor Heravi. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract.

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.

1. 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 [4–7]. 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.

In this context, we wish to describe a convenient and simple methodology for the synthesis of bis-indolylindane-1,3-dione (by reacting ninhydrin with 3 substituted/unsubstituted indoles), 2-(1′,3′-dihydro-1H-[2,3′]biindolyl-2′-ylidene)-indan-1,3-diones, indene-1,3(2H)-denies (from the reaction of ninhydrin, 1,2-phenylendiamine, and indole), and 2,2-bis(4-(dimethylamino)phenyl)-1H-indene-1,3(2H)-diones (from the reaction of ninhydrin with N,N-dimethylaniline). The reactions were carried out using [Hbim]BF₄ ionic liquid as green solvent. The novelty of the methodology lies in its eco-friendly operation, the formation of structurally unique molecules, short reaction time, and excellent yield.

2. 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. ¹H and ¹³C NMR spectra were measured using deuterochloroform as solvent, and chemical shifts were measured relatively to residual solvent or CFCl₃ as an internal standard for ¹⁹F 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.

2.2. General Procedure for the Synthesis of Bis-indolylindane-1,3-dione, 2-(1′,3′-Dihydro-1H-[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]BF₄. 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.

Spectroscopic data of new products are given below.

2.2.1. 2,2-Bis(5-fluoro-1H-indol-3-yl)-1H-indene-1,3(2H)-dione 3b (Table 1, Entry 2)

Table 1: Synthesis of bis-indolylindane-1,3-dione, 2-(1′,3′-dihydro-1H-[2,3′]biindolyl-2′-ylidene)-indan-1,3-diones in the presence of [Hbim]BF₄ ionic medium.

Entry
R¹
R²
R³
Product
Time (min)
Yield (%)a
Melting point

Report, m.p. (°C)
Li. m.p. (°C) [Ref]

1
H
H
H
3a
5
95
207–209
208–210 [9]

2
H
H
F
3b
10
90
121–123
Prepared for the first time

3
H
H
Br
3c
8
93
105–107
104–106 [9]

4
H
CH₃
H
3d
4
97
107–109
108–110 [9]

5
CH₃
H
H
3e
3
97
233–235
232–234 [9]

Yield refers to pure products after crystallization.

Yellow prisms, mp = 121–123°C, IR (KBr): , 1706, 1254, 755 cm⁻¹; ¹H NMR (500 MHz, DMSO-): (s, 2H), 7.38 (m, 2H), 7.41 (m, 2H), 7.45 (s, 2H), 7.76 (m, 1H), 7.87 (m, 1H), 8.11 (m, 1H), 8.25 (m, 1H), 12.54 (s, 2H, −NH) ppm; ¹³C NMR (125 MHz, DMSO-): (C), 111.7 (2 × C), 112.5 (2 × C), 115.1 (2 × CH), 125.9 (2 × CH), 127.2 (4 × CH), 128.8 (2 × CH), 129.5 (2 × C), 132.5 (2 × CH), 137.8 (2 × C), 151.6 (d,  Hz, 2 × C–F), 197.8 (2 × CO) ppm; ¹⁹F NMR (DMSO-, 470 MHz): −73.25; MS (EI), (%) = 412 (M⁺, 27), 144 (65); HRMS (EI) Found: M⁺, 412.1008. C₂₅H₁₅F₃N₂S requires M⁺, 412.1011; Anal Calcd. for C₂₅H₁₅F₃N₂S, C, 72.81; H, 3.42; N, 6.79. Found: C, 72.90; H, 3.41; N, 6.71.

2.2.2. 11,11-Bis-(5-fluoro-1H-indol-3-yl)-11H-indeno[1,2-b]quinoxaline 5ab (Table 2, Entry 2)

Table 2: Preparation of 5 in ionic liquid [Hbim]BF₄.

Entry
R¹
R²
R³
R⁴
Product
Time (min)
Yield (%)a
Melting Point

Report, m.p. (°C)
Li. m.p. (°C) [Ref]

1
H
H
H
H
5aa
10
93
277–279
276–278 [9]

2
H
H
F
H
5ab
12
90
224–226
Prepared for the first time

3
H
H
Br
H
5ac
8
92
275–277
274–276 [9]

4
H
CH₃
H
H
5ad
7
94
195–197
Prepared for the first time

5
CH₃
H
H
H
5ae
5
95
183–185
182–184 [9]

6
H
H
H
CH₃
5ba
7
93
217–219
218–220 [9]

7
H
H
F
CH₃
5bb
7
92
210–212
Prepared for the first time

8
H
H
Br
CH₃
5bc
7
95
219–221
Prepared for the first time

9
H
CH₃
H
CH₃
5bd
5
97
205–207
204–206 [9]

10
CH₃
H
H
CH₃
5be
3
95
171–173
170–172 [9]

11
H
H
H
Cl
5ca
10
94
228–230
Prepared for the first time

12
H
H
F
Cl
5cb
15
91
199–201
Prepared for the first time

13
H
H
Br
Cl
5cc
8
93
223–225
Prepared for the first time

14
H
CH₃
H
Cl
5cd
7
94
253–255
Prepared for the first time

15
CH₃
H
H
Cl
5ce
5
95
185–187
186–188 [9]

Yield refers to pure products after crystallization.

Yellow prisms, mp = 224–226°C, IR (KBr): , 1459, 1121, 763 cm⁻¹; ¹H NMR (500 MHz, DMSO-): (s, 2H), 7.31 (m, 2H), 7.52 (m, 6H), 7.85 (d, 1H,  Hz), 8.03 (d, 1H,  Hz), 8.11 (s, 2H), 8.19 (d, 1H,  Hz), 8.62 (d, 1H,  Hz), 12.45 (s, 2H, −NH) ppm; ¹³C NMR (125 MHz, DMSO-): (C), 112.4 (2 × C), 116.8 (2 × CH), 117.9 (2 × C), 123.7 (CH), 125.8 (CH), 126.7 (CH), 127.5 (CH), 128.0 (CH), 129.2 (2 × C), 129.6 (CH), 130.2 (CH), 130.8 (CH), 130.9 (CH), 132.2 (CH), 133.2 (CH), 133.9 (CH), 137.5 (C), 138.2 (C), 138.9 (C), 141.2 (C), 151.8 (d,  Hz, 2 × C–F), 154.2 (C), 168.5 (C) ppm; ¹⁹F NMR (DMSO-, 470 MHz): −78.45; MS (EI), (%) = 484 (M⁺, 18), 184 (55); HRMS (EI) Found: M⁺, 485.1507. C₃₁H₁₈F₂N₄ requires M⁺, 484.1501; Anal Calcd. for C₃₁H₁₈F₂N₄, C, 76.85; H, 3.74; N, 11.56. Found: C, 76.94; H, 3.61; N, 11.60.

2.2.3. 11,11-Bis(2-methyl-1H-indol-3-yl)-11H-indeno[1,2-b]quinoxaline 5ad (Table 2, Entry 4)

Green prisms, mp = 195–197°C, IR (KBr): , 2954, 1468, 763 cm⁻¹; ¹H NMR (500 MHz, DMSO-): (s, 6H, CH₃), 6.98 (s, 2H), 7.02 (t, 2H,  Hz), 7.12 (t, 2H,  Hz), 7.31 (m, 2H), 7.54 (t, 1H,  Hz), 7.68 (m, 4H), 7.94 (t, 1H,  Hz), 8.01 (m, 2H), 8.09 (m, 2H), 8.12 (d, 1H,  Hz), 8.41 (d, 1H,  Hz), 8.41 (d, 1H,  Hz) ppm; ¹³C NMR (125 MHz, DMSO-): (CH₃), 33.1 (CH₃), 54.2 (C), 110.1 (2 × CH), 115.4 (2 × C), 117.9 (2 × CH), 122.5 (2 × CH), 123.4 (2 × CH), 124.2 (2 × CH), 126.2 (C), 126.7 (CH), 128.0 (CH), 128.6 (CH), 128.9 (CH), 129.4 (C), 129.5 (2 × CH), 130.4 (C), 137.2 (C), 137.8 (2 × C), 140.0 (C), 141.2 (C), 152.1 (2 × C), 152.4 (C), 159.4 (C) ppm; MS (EI), (%) = 476 (M⁺, 9), 210 (43); HRMS (EI) Found: M⁺, 476.2008. C₃₃H₂₄N₄ requires M⁺, 476.2001; Anal Calcd. for C₃₃H₂₄N₄, C, 83.17; H, 5.08; N, 11.76. Found: C, 83.14; H, 5.11; N, 11.81.

2.2.4. 11,11-Bis(5-fluoro-1H-indol-3-yl)-7,8-dimethyl-11H-indeno[1,2-b]quinoxaline 5bb (Table 2, Entry 7)

Brown needles, mp = 210–212°C, IR (KBr): , 2935, 1454, 746 cm⁻¹; ¹H NMR (500 MHz, DMSO-): (s, 6H, CH₃), 6.81 (s, 2H), 6.91 (m, 4H), 7.21 (m, 2H), 7.55 (d, 1H,  Hz), 7.65 (d, 1H,  Hz), 7.85 (s, 2H), 7.92 (d, 1H,  Hz), 8.12 (d, 1H,  Hz), 11.86 (s, 2H, −NH) ppm; ¹³C NMR (125 MHz, DMSO-): (2 × CH₃), 54.7 (C), 110.4 (2 × CH), 114.8 (2 × C), 116.9 (2 × CH), 122.5 (2 × CH), 124.8 (CH), 125.8 (CH), 126.5 (CH), 127.5 (2 × C), 128.2 (CH), 129.0 (CH), 130.1 (CH), 130.4 (CH), 131.9 (CH), 131.8 (C), 132.2 (C), 133.4 (C), 135.5 (C), 137.2 (2 × C), 139.4 (C), 140.2 (C), 152.8 (d, Hz, 2 × C–F), 155.4 (C), 169.7 (C) ppm; ¹⁹F NMR (DMSO-, 470 MHz): −76.78; MS (EI), (%) = 512 (M⁺, 15), 252 (51); HRMS (EI) Found: M⁺, 512.1804. C₃₃H₂₂F₂N₄ requires M⁺, 512.1807; Anal Calcd. for C₃₃H₂₂F₂N₄, C, 77.33; H, 4.33; N, 10.93. Found: C, 77.41; H, 4.31; N, 11.01.

2.2.5. 11,11-Bis(5-bromo-1H-indol-3-yl)-7,8-dimethyl-11H-indeno[1,2-b]quinoxaline 5bc (Table 2, Entry 8)

Green needles, mp = 219–221°C, IR (KBr): , 2987, 1472, 761 cm⁻¹; ¹H NMR (500 MHz, DMSO-): (s, 6H, CH₃), 7.14 (s, 2H), 7.31 (m, 2H), 7.51 (m, 6H), 7.84 (d, 1H,  Hz), 7.86 (d, 1H,  Hz), 7.98 (s, 2H), 8.14 (d, 1H,  Hz), 8.24 (d, 1H,  Hz), 12.24 (s, 2H, −NH) ppm; ¹³C NMR  (125 MHz, DMSO-): (2 × CH₃), 55.7 (C), 111.4 (2 × C), 115.7 (2 × CH), 117.5 (2 × C), 122.6 (2 × CH), 125.6 (CH), 126.6 (CH), 126.5 (CH), 127.5 (2 × C), 128.2 (CH), 129.0 (CH), 130.1 (CH), 130.4 (CH), 131.9 (CH), 128.5 (CH), 131.2 (2 × C), 131.6 (CH), 137.5 (2 × C), 138.4 (C), 141.2 (C), 143.8 (2 × C), 153.6 (C), 167.2 (C) ppm; MS (EI), (%) = 634 (M⁺, 25), 384 (75); HRMS (EI) Found: M⁺, 632.0215. C₃₃H₂₂BrN₄ requires M⁺, 632.0211; Anal Calcd. for C₃₃H₂₂BrN₄, C, 62.48; H, 3.50; N, 8.83. Found: C, 62.51; H, 3.41; N, 8.89.

2.2.6. 7,8-Dichloro-11,11-di(1H-indol-3-yl)-11H-indeno[1,2-b]quinoxaline 5ca (Table 2, Entry 11)

Yellow needles, mp = 228–230°C, IR (KBr): , 1438, 747 cm⁻¹; ¹H NMR (500 MHz, DMSO-): (s, 2H), 6.93 (m, 2H), 7.06 (m, 2H), 7.32 (m, 4H), 7.64 (m, 2H), 7.75 (d, 1H,  Hz), 7.96 (d, 1H,  Hz), 8.09 (s, 1H), 8.14 (d, 1H,  Hz), 12.24 (s, 2H, −NH) ppm; ¹³C NMR (125 MHz, DMSO-): (C), 109.4 (2 × CH), 115.4 (2 × C), 119.4 (2 × CH), 122.7 (CH), 125.9 (CH), 126.8 (2 × CH), 127.5 (2 × C), 127.9 (2 × CH), 1285 (CH), 129.4 (CH), 130.2 (CH), 130.8 (CH), 131.5 (2 × CH), 131.8 (C), 130.9 (C), 137.5 (2 × C), 138.8 (C), 140.7 (C), 142.8 (2 × C), 158.6 (C), 166.2 (C) ppm; MS (EI), (%) = 517 (M⁺, 22), 257 (65); HRMS (EI) Found: M⁺, 516.0903. C₃₁H₁₈Cl₂N₄ requires M⁺, 516.0908; Anal Calcd. for C₃₁H₁₈Cl₂N₄, C, 71.96; H, 13.70; N, 10.83. Found: C, 71.89; H, 13.61; N, 10.89.

2.2.7. 7,8-Dichloro-11,11-bis(5-fluoro-1H-indol-3-yl)-11H-indeno[1,2-b]quinoxaline 5cb (Table 2, Entry 12)

Green needles, mp = 199–201°C, IR (KBr): , 1452, 729 cm⁻¹; ¹H NMR (500 MHz, DMSO-): (s, 2H), 7.01 (m, 2H), 7.12 (m, 2H), 7.42 (m, 3H), 7.56 (m, 2H), 7.63 (d, 1H,  Hz), 7.89 (d, 1H,  Hz), 8.10 (s, 1H), 12.37 (s, 2H, −NH) ppm; ¹³C NMR (125 MHz, DMSO-): (C), 107.9 (2 × CH), 113.6 (2 × C), 117.7 (CH), 121.7 (CH), 123.9 (CH), 124.7 (2 × CH), 126.7 (2 × C), 128.3 (2 × CH), 128.8 (CH), 129.0 (CH), 131.2 (CH), 131.8 (CH), 132.5 (2 × CH), 133.5 (C), 134.8 (C), 136.9 (2×C), 137.8 (2 × C), 141.7 (C), 144.6 (2 × C), 156.9 (d,  Hz, 2 × C–F), 168.0 (C) ppm; ¹⁹F NMR (DMSO-, 470 MHz): −73.68; MS (EI), (%) = 552 (M⁺, 12), 292 (65); HRMS (EI) Found: M⁺, 552.071012. C₃₁H₁₆Cl₂F₂N₄ requires M⁺, 552.0710; Anal Calcd. for C₃₁H₁₆Cl₂F₂N₄, C, 67.28; H, 2.91; N, 10.12. Found: C, 67.34; H, 2.98; N, 10.21.

2.2.8. 11,11-Bis(5-bromo-1H-indol-3-yl)-7,8-dichloro-11H-indeno[1,2-b]quinoxaline 5cc (Table 2, Entry 13)

Green needles, mp = 223–225°C, IR (KBr): , 1434, 739 cm⁻¹; ¹H NMR (500 MHz, DMSO-): (s, 2H), 6.89 (m, 2H), 6.89 (m, 2H), 7.12 (m, 3H), 7.35 (m, 2H), 7.56 (d, 1H,  Hz), 7.69 (d, 1H,  Hz), 8.05 (s, 1H), 12.22 (s, 2H, −NH) ppm; ¹³C NMR (125 MHz, DMSO-): (C), 111.2 (2 × CH), 114.6 (2 × C), 118.8 (CH), 120.8 (CH), 122.7 (CH), 123.4 (2 × CH), 125.6 (2 × C), 126.8 (2 × CH), 127.6 (CH), 128.2 (CH), 130.2 (CH), 131.0 (CH), 133.5 (CH), 133.8 (C), 135.4 (C), 136.4 (2 × C), 137.4 (2 × C), 140.6 (C), 143.8 (2 × C), 155.6 (d, 2 × C), 169.4 (C) ppm; MS (EI), (%) = 675 (M⁺, 11), 415 (34); HRMS (EI) Found: M⁺, 671.9112. C₃₁H₁₆Br₂Cl₂N₄ requires M⁺, 671.9110; Anal Calcd. for C₃₁H₁₆Br₂Cl₂N₄, C, 55.14; H, 2.39; N, 8.30. Found: C, 55.23; H, 2.38; N, 8.33.

2.2.9. 7,8-Dichloro-11,11-bis(2-methyl-1H-indol-3-yl)-11H-indeno[1,2-b]quinoxaline 5cd (Table 2, Entry 14)

Yellow needles, mp = 253–255°C, IR (KBr): , 2982, 1456, 740 cm⁻¹; ¹H NMR (500 MHz, DMSO-): (s, 3H, CH₃), 2.42 (s, 3H, CH₃), 6.89 (s, 2H), 6.91 (m, 2H), 7.01 (m, 2H), 7.21 (m, 3H), 7.30 (m, 2H), 7.46 (d, 1H,  Hz), 7.51 (d, 1H,  Hz), 8.12 (s, 1H), 12.43 (s, 2H, −NH) ppm; ¹³C NMR (125 MHz, DMSO-): (CH₃), 21.6 (CH₃), 55.1 (C), 111.2 (2 × CH), 114.6 (2 × C), 118.8 (CH), 120.8 (CH), 122.7 (CH), 123.4 (2 × CH), 125.6 (2 × C), 126.8 (2 × CH), 127.6 (CH), 128.2 (CH), 130.2 (CH), 131.0 (CH), 133.5 (CH), 133.8 (C), 135.4 (C), 136.4 (2 × C), 137.4 (2 × C), 140.6 (C), 143.8 (2 × C), 155.6 (d, 2 × C), 169.4 (C) ppm; MS (EI), (%) = 545 (M⁺, 10), 285 (35); HRMS (EI) Found: M⁺, 544.1200. C₃₃H₂₂Cl₂N₄ requires M⁺, 544.1205; Anal Calcd. for C₃₃H₂₂Cl₂N₄, C, 72.66; H, 4.07; N, 10.27. Found: C, 72.69; H, 4.08; N, 10.33.

2.2.10. 2,2-Bis(4-(dimethylamino)phenyl)-1H-indene-1,3(2H)-dione 7a (Table 3, Entry 1)

Table 3: Preparation of 7 in ionic liquid [Hbim]BF₄.

Entry
R⁵
Product
Time (min)
Yield (%)a
Melting point (°C)

1
H
7a
15
95
New

2
m-CH₃
7b
5
97
New

3
m-Cl
7c
10
93
New

Yield refers to pure products after crystallization.

Brown needles, mp = 211–213°C, IR (KBr): , 2984, 1715, 1625, 1451, 749 cm⁻¹; ¹H NMR (500 MHz, DMSO-): (s, 6H, 2 × CH₃), 3.35 (s, 6H, 2 × CH₃), 6.72 (d, 4H), 6.98 (m, 4H), 8.21 (d, 2H,  Hz), 8.13 (d, 2H,  Hz) ppm; ¹³C NMR (125 MHz, DMSO-): (2 × CH₃), 23.1 (2 × CH₃), 80.1 (C), 110.2 (4 × CH), 113.4 (2 × C), 114.8 (2 × CH), 115.7 (4 × CH), 117.6 (2 × CH), 145.2 (2C), 196.8 (2C) ppm; MS (EI), (%) = 384 (M⁺, 15), 144 (26); HRMS (EI) Found: M⁺, 384.1819. C₂₅H₂₄N₂O₂ requires M⁺, 384.1821; Anal Calcd. for C₂₅H₂₄N₂O₂, C, 78.10; H, 6.29; N, 7.29. Found: C, 72.69; H, 4.08; N, 10.33.

2.2.11. 2,2-Bis(4-(dimethylamino)-3-methylphenyl)-1H-indene-1,3(2H)-dione 7b (Table 3, Entry 2)

Yellow needles, mp = 231–233°C, IR (KBr): , 1705, 1456, 745 cm⁻¹; ¹H NMR (500 MHz, DMSO-): (s, 3H, CH₃), 3.20 (s, 6H, 2 × CH₃), 3.35 (s, 6H, 2 × CH₃), 6.72 (d, 3H), 6.98 (m, 3H), 8.21 (d, 2H,  Hz), 8.13 (d, 2H,  Hz) ppm; ¹³C NMR (125 MHz, DMSO-): (CH₃), 22.3 (2 × CH₃), 23.1 (2 × CH₃), 80.1 (C), 110.2 (3 × CH), 113.4 (3 × C), 114.8 (3 × CH), 115.7 (3 × CH), 117.6 (2 × CH), 145.2 (2C), 196.8 (2C) ppm; MS (EI), (%) = 412 (M⁺, 17), 172 (35); HRMS (EI) Found: M⁺, 412.2209. C₂₇H₂₈N₂O₂ requires M⁺, 412.2211; Anal Calcd. for C₂₇H₂₈N₂O₂, C, 78.61; H, 6.84; N, 6.79. Found: C, 72.70; H, 6.90; N, 6.81.

2.2.12. 2,2-Bis(3-chloro-4-(dimethylamino)phenyl)-1H-indene-1,3(2H)-dione 7c (Table 3, Entry 3)

Yellow needles, mp = 225–227°C, IR (KBr): , 1712, 1456, 729 cm⁻¹; ¹H NMR (500 MHz, DMSO-): (s, 6H, 2 × CH₃), 3.29 (s, 6H, 2 × CH₃), 6.81 (d, 3H), 6.92 (m, 3H), 8.04 (d, 2H,  Hz), 8.15 (d, 2H,  Hz) ppm; ¹³C NMR (125 MHz, DMSO-): (2 × CH₃), 23.1 (2 × CH₃), 80.1 (C), 110.2 (3 × CH), 113.4 (3 × C), 114.8 (3 × CH), 115.7 (3 × CH), 117.6 (2 × CH), 145.2 (2C), 196.8 (2C) ppm; MS (EI), (%) = 453 (M⁺, 14), 213 (75); HRMS (EI) Found: M⁺, 412.2209. C₂₅H₂₂Cl₂N₂O₂ requires M⁺, 412.2211; Anal Calcd. For C₂₅H₂₂Cl₂N₂O₂, 66.23; H, 4.89; N, 6.18. Found: C, 66.27; H, 4.91; N, 6.14.

3. Results and Discussions

With an ever increasing quest for the exploration of newer reactions in ionic liquids, the ionic liquid plays the dual role of solvent and promoter. Herein, we wish to report, for the first time, the use of [Hbim]BF₄ ionic liquid as novel and recyclable polar reaction media for the synthesis of bis-indolylindane-1,3-dione, 2-(1′,3′-dihydro-1H-[2,3′]biindolyl-2′-ylidene)-indan-1,3-diones, and 2,2-bis(4-(dimethylamino)phenyl)-1H-indene-1,3(2H)-denies (Scheme 1).

Scheme 1: Synthesis of bis-indolylindane-1,3-dione, 2-(1′,3′-dihydro-1H-[2,3′]biindolyl-2′-ylidene)-indan-1,3-diones, 5, and 7 in the presence of [Hbim]BF₄ ionic medium.

First, 1 mmol ninhydrin (1) and 2 mmol different substituted indole derivatives (2a–e) were added to a 20 mL round bottom flask containing 2 mL [Hbim]BF₄ ionic media. The resulting mixture stirred the appropriate time to afford his-indolylindane-1,3-dione, 2-(1′,3′-dihydro-1H-[2,3′]biindolyl-2′-ylidene)-indan-1,3-diones 3(a–e) in excellent yield (Table 1). Differently substituted indole derivatives (2a–e) were reacted with ninhydrin (1). Of these, 5-fluoro (2b), 5-bromo (2c), 2-methyl (2d), 1-methyl (2e) indoles reacted smoothly to produce novel bis-indolylindane-1,3-dione, 2-(1′,3′-dihydro-1H-[2,3′]biindolyl-2′-ylidene)-indan-1,3-diones (Table 1, entries 2–5). The characteristic quaternary carbon signals 3(a–e) clearly indicate the attachment of two indole moieties at C-2 of ninhydrin.

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).

Reaction ninhydrin (1, 1 mmol) and different substituted N,N-dimethyl aniline 6(a–c) went smoothly in the ionic liquid [Hbim]BF₄ under solvent free conditions to afford the corresponding products 7(a–c) in high yields (Table 3, entries 1–3).

Ninhydrin is in equilibrium with indane-1,2,3-trione (1b). The nucleophilic substitution at C-3 of indole, produced intermediate B, via 1,3-migration hydrogen and aromatization of the indole ring produced C intermediate, which was attacked by another indole moiety and dehydration to form intermediate D. Finally, intermediate C after hydrogen remove formed the bis-indolylindane-1,3-dione, 2-(1′,3′-dihydro-1H-[2,3']biindolyl-2′-ylidene)-indan-1,3-diones 3(a–e) (Scheme 2).

Scheme 2: Plausible mechanism synthesis of bis-indolylindane-1,3-dione, 2-(1′,3′-dihydro-1H-[2,3′]biindolyl-2′-ylidene)-indan-1,3-diones, in the presence of [Hbim]BF₄ ionic medium.

In this case, initially the condensation of ninhydrin (1) and 1,2-phenylenediamine 4(a–c) took place to produce the intermediate E→F→A, which reacted with 2 mol of indoles 2(a–e) via the intermediate A to generate 5aa–5ae, 5ba–5be, 5ca–5ce in high yield (Table 2, entries 1-15) (Scheme 3).

Scheme 3: Plausible mechanism for the synthesis of indene-1,3(2H)-denies in the presence of [Hbim]BF₄ ionic medium.

Reaction ninhydrin (1) with different substituted N, N-dimethyl aniline 6(a–c) via intermediates transformation G→H→I, finally with hydrogen removes and aromatization to produce 7(a–c) (Scheme 4).

Scheme 4: Plausible mechanism for the synthesis of 2,2-bis(4-(dimethylamino)phenyl)-1H-indene-1,3(2H)-denies in the presence of [Hbim]BF₄ ionic medium.

We also investigated the recycling of the ionic liquid [Hbim]BF₄ 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-1H-indole, 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, and 3 (Figure 2) (see Supplementary data available online at http://dx.doi.org/10.1155/2013/528329). From the values, it is clearly seen that the protocols are atom economy and generate the least amount of waste which is a complimentary ecofriendly aspect of catalyst. The results show that present ionic liquids such as [Hbim]BF₄ are efficient catalyst with respect to the low reaction times and the high yields.

Figure 1: Recyclability of [Hbim]BF₄ ionic liquid as catalyst.

Figure 2: Atomic economy of products.

4. Conclusion

In summary, we describe a novel use of ionic liquids for the synthesis of an efficient synthesis of bis-indolylindane-1,3-dione, 2-(1′,3′-dihydro-1H-[2,3′]biindolyl-2′-ylidene)-indan-1,3-diones, and 2,2-bis(4-(dimethylamino)phenyl)-1H-indene-1,3(2H)-denies using [Hbim]BF₄ ionic medium in excellent yields. The notable features of this procedure are high conversions, operational simplicity, good reaction rates, clean reaction profiles, and ease of isolation of products, which make this process quite simple, convenient, and environmentally benign for the synthesized compounds.

Highlights

(i)An efficient method for the synthesis of bis-indolylindane-1,3-dione, 2-(1′,3′-dihydro-1H-[2, 3′]biindolyl-2′-ylidene)-indan-1,3-diones and 2,2-bis(4-(dimethylamino)phenyl)-1H-indene-1,3(2H)-denies using [Hbim] BF₄ ionic mediumfor a wide variety of substituted products.(ii)Easy workup and clean reaction.(iii)Methodology is superior in terms of scope, starting material availability brevity, and being ecofriendly.(iv)Recyclability of catalyst.(v)High atomic economy.(vi)Relatively less toxic and biodegradable ionic liquid.

Acknowledgment

The author is thankful to Payame Noor University, Tehran, Iran for the support of this research.

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