An appropriate one-pot synthesis of 4-aryl-2-naphthalen-2-yl-5H-indeno [1,2-b]pyridin-5-ones usingthiourea dioxide as an efficient and reusableorganocatalyst

Majid Ghashang • Syed Sheik Mansoor •

Kuppan Logaiya • Krishnamoorthy Aswin

Received: 9 March 2014 / Accepted: 7 June 2014

� Springer Science+Business Media Dordrecht 2014

Abstract A new one-pot synthesis of 4-aryl-2-naphthalen-2-yl-5H-indeno[1,2-

b]pyridin-5-ones from the condensation of aryl aldehydes, 1-naphthalen-2-yl-etha-

none, 1,3-indandione and ammonium acetate in the presence of thiourea dioxide in

water at 80 �C is described. The present methodology offers several advantages,

such as good yields, atom economy, short reaction times and a recyclable catalyst

with a very easy work-up.

Keywords Thiourea dioxide (TUD) � 1,3-Indandione � Indeno[1,2-b]pyridines �1-Naphthalen-2-yl-ethanone

Introduction

The development of new and efficient synthetic methodologies for the rapid

construction of potentially bio-active compounds constitutes a major challenge for

chemists in organic synthesis. Multi-component reactions (MCRs) are of increasing

importance in organic and medicinal chemistry, because the strategies of MCR offer

significant advantages over conventional linear-type syntheses. MCRs play an

important role in combinatorial chemistry because of their ability to synthesize

small drug-like molecules with several degrees of structural diversity [1–3].

Many indenopyridine derivatives, being the core structural unit in a wide range of

natural products, has attracted much research in recent times [4]. These compounds

M. Ghashang

Faculty of Sciences, Najafabad Branch, Islamic Azad University,

P.O. Box: 517, Najafabad, Esfahan, Iran

S. S. Mansoor (&) � K. Logaiya � K. Aswin

Bioactive Organic Molecule Synthetic Unit, Research Department of Chemistry, C. Abdul Hakeem

College, Melvisharam 632 509, Tamil Nadu, India

e-mail: smansoors2000@yahoo.co.in; mansoorcah@gmail.com

123

Res Chem Intermed

DOI 10.1007/s11164-014-1742-2

show powerful antimicrobial, DNA damaging, and anti-malarial effects against P.

falciparum and also act as DNA-modifying agents [5, 6]. Mass-directed isolation of the

CH2Cl2/MeOH extract from the roots of the Australian tree Mitrephora diversifolia

resulted in the purification of the new azafluorenone alkaloid 5,8-dihydroxy-6-

methoxyonychine. This compound exhibited activity against the parasite P. falciparum

[7]. Azafluorenone derivatives have been reported to possess phosphatidyl-inositol-

specific phospholipase C activation in C6 glioma cells [8]. Bioactive azafluorenone

alkaloids from P. debilis found to exhibit antimicrobial, antimalarial and cytotoxic

activities [9]. It is recently reported that 6,8-dihydroxy-7-methoxy-1-methyl-azafluor-

enone (DMMA), a purified compound from Polyalthia cerasoides roots, is cytotoxic to

various cancer cell lines [10]. Therefore, these compounds have distinguished

themselves as heterocycles of profound chemical and biological significance.

Consequently, many methods for the synthesis of the 5H-indeno[1,2-b]pyridin-5-

ones have been reported, including the use of oxidative intramolecular Heck

cyclization using Pd(0) [11], using ceric ammonium nitrate (CAN) as catalyst [12],

using L-proline as catalyst [13], microwave irradiation [14], molecular hybridization

approach [15] and Pummerer reaction of imido sulfoxides bearing tethered alkenyl

groups [16]. An efficient methodology for the synthesis of new and highly

functionalized 2-azafluorenones via a three-component domino reaction involving

C1-aryl acylation, C3-thiolation, and C4-cyanation has been developed [17].

However, most of the reported procedures have some limitations, such as harsh

reaction conditions, the use of expensive reagents or poor yields. In addition, most of

the earlier-reported methodologies require elevated temperature created by micro-

wave-oven irradiation. As a consequence, more efficient and versatile methodologies

which are tolerable to a large variety of functional groups are still needed. Recently, in

our laboratory, we have synthesized a series of indeno[1,2-b]pyridine derivatives by

the MCR of 1,3-diphenyl-2-propen-1-one, 1,3-indandione, and ammonium acetate at

60 �C using pentafluorophenyl ammonium triflate (PFPAT) as catalyst [18].

Organocatalysis become a new research area in synthetic chemistry several years

ago, which is one of the most important contents for green chemistry. Driven by

environmental concern, there is great interest and need for cheap and readily

available, recyclable and reusable, non-metallic small molecule catalysts [19].

Recently, TUD has emerged as a promising novel organo-catalyst in the one-pot

synthesis of a library of novel heterocyclic compounds [20], hydrolysis of imines

[21], synthesis of naphthopyrans [22], synthesis of pyrano[4,3-b]pyrans [23] and

synthesis of structurally diverse dihydropyrido[2,3-d]pyrimidine-2,4-diones [24].

TUD is easily prepared by the oxidation of thiourea with hydrogen peroxide [25]. It

is highly stable and possesses the ability to activate organic substrates through

hydrogen bonding. In addition, TUD is insoluble in common organic solvents and

therefore can easily be recovered at the end of the reaction for reuse.

In our continued interest in the synthesis of heterocyclic compounds on the

development of environmentally friendly procedures for the synthesis of biologically

active molecules [26–28], we now describe the synthesis of 4-aryl-2-naphthalen-2-yl-

5H-indeno[1,2-b]pyridin-5-ones using aryl aldehydes, 1-naphthalen-2-yl-ethanone,

1,3-indandione and ammonium acetate in the presence of TUD as an efficient organo-

catalyst in water (Scheme 1).

M. Ghashang et al.

123

Experimental

Apparatus and analysis

Chemicals were purchased from Merck, Fluka and Aldrich. All yields refer to

isolated products unless otherwise stated. 1H NMR (500 MHz) and 13C NMR

(125 MHz) spectra were obtained using a Bruker DRX-500 Avance at ambient

temperature, using TMS as internal standard. FT-IR spectra were obtained as KBr

discs on Shimadzu spectrometer. Mass spectra were determined on a Varion–Saturn

2000 GC/MS instrument. Elemental analysis were measured by means of a Perkin

Elmer 2400 CHN elemental analyzer flowchart.

General experimental procedure for the synthesis of indeno[1,2-b]pyridine

derivatives

In a 25-mL round-bottomed flask, aldehydes (1 mmol), 1-naphthalen-2-yl-ethanone

(1 mmol), 1,3-indandione (1 mmol) and ammonium acetate (1.3 mmol) were stirred

in the presence of 10 mol% of TUD in water (5 mL) at 80 �C for the stipulated

time. The progress of the reaction was monitored by TLC. After completion of the

reaction, the reaction mixture was diluted with water (10 mL) and extracted with

ethyl acetate (3 9 10 mL). The organic layer was dried over anhydrous Na2SO4,

concentrated and recrystallised from hot ethanol to afford the pure product. The

remaining thiourea dioxide (TUD) was reused for subsequent runs. The IR, 1H

NMR, 13C NMR, mass and elemental analysis data of the synthesized compounds

are given below.

Spectral data for the synthesized compounds are presented below (4a–l)

4-(4-Chlorophenyl)-2-naphthalen-2-yl-5H-indeno[1,2-b]pyridin-5-one (4a)

IR (KBr, cm-1): 3,047, 2,946, 2,835, 1,711, 1,600, 1,515, 1,363, 1,253, 1,153, 827,

752; 1H NMR (500 MHz, DMSO-d6) d: 7.17–7.43 (m, 8H, Ar–H), 7.66 (s, 1H, Py–

H

O

R

CH3

O

O

O

NH4OAc+

1a-l

2

3

S

H2N NH2

OO

N

O

R

Water, 80 oC

4a-l

Scheme 1 TUD catalysed one-pot synthesis of 4-aryl-2-naphthalen-2-yl-5H-indeno[1,2-b]pyridin-5-onederivatives

An appropriate one-pot synthesis

123

H), 7.77–7.90 (m, 4H, Ar–H), 8.07–8.11 (m, 3H, Ar–H) ppm; 13C NMR (125 MHz,

DMSO-d6) d: 121.7, 123.1, 123.8, 124.3, 125.3, 125.6. 126.5, 127.4, 128.2, 128.5,

129.2, 129.5, 129.9, 130.5, 131.8, 135.3, 135.7, 139.5, 141.6, 142.4, 142.6, 146.2,

147.6, 162.5, 163.7, 192.6 ppm; MS(ESI): m/z 418 (M ? H)?; Anal. Calcd for

C28H16ClNO: C, 80.49; H, 3.83; N, 3.35 %. Found: C, 80.37; H, 3.77; N, 3.36 %.

4-(4-Methylphenyl)-2-naphthalen-2-yl-5H-indeno[1,2-b]pyridin-5-one (4b)

IR (KBr, cm-1): 3,052, 2,952, 2,843, 1,713, 1,601, 1,511, 1,368, 1,269, 1,159, 827,

757; 1H NMR (500 MHz, DMSO-d6) d: 2.26 (s, 3H, CH3), 7.19–7.44 (m, 8H, Ar–

H), 7.55 (s, 1H, Py–H), 7.72–7.89 (m, 4H, Ar–H), 8.05–8.12 (m, 3H, Ar–H) ppm;13C NMR (125 MHz, DMSO-d6) d: 18.0, 122.3, 123.4, 123.9, 124.7, 125.3, 125.6.

126.7, 127.3, 128.7, 129.4, 129.7, 130.5, 131.7, 135.4, 135.6, 139.7, 141.9, 142.9,

146.6, 147.8, 162.8, 163.6, 191.8 ppm; MS(ESI): m/z 398 (M ? H)?; Anal. Calcd

for C29H19NO: C, 87.65; H, 4.78; N, 3.52 %. Found: C, 87.55; H, 4.71; N, 3.44 %.

4-(4-Methoxyphenyl)-2-naphthalen-2-yl-5H-indeno[1,2-b]pyridin-5-one (4c)

IR (KBr, cm-1): 3,044, 2,954, 2,844, 1,713, 1,603, 1,507, 1,367, 1,255, 1,155, 825,

755; 1H NMR (500 MHz, DMSO-d6) d: 3.76 (s, 3H, OCH3), 7.11–7.27 (m, 8H, Ar–

H), 7.70 (s, 1H, Py–H), 7.80–7.93 (m, 4H, Ar–H), 8.00–8.15 (m, 3H, Ar–H) ppm;13C NMR (125 MHz, DMSO-d6) d: 54.8, 121.3, 123.5, 123.7, 124.3, 125.2, 125.6.

126.5, 127.9, 128.6, 129.3, 129.7, 129.9, 131.1, 135.3, 135.8, 139.4, 141.7, 142.5,

146.7, 147.8, 162.2, 163.7, 191.7 ppm; MS(ESI): m/z 414 (M ? H)?; Anal. Calcd

for C29H19NO2: C, 84.26; H, 4.60; N, 3.39 %. Found: C, 84.22; H, 4.54; N, 3.36 %.

4-(4-Hydroxyphenyl)-2-naphthalen-2-yl-5H-indeno[1,2-b]pyridin-5-one (4d)

IR (KBr, cm-1): 3,353, 3,043, 2,942, 2,832, 1,717, 1,609, 1,501, 1,367, 1,258,

1,144, 820, 757; 1H NMR (500 MHz, DMSO-d6) d: 7.17–7.33 (m, 8H, Ar–H), 7.58

(s, 1H, Py–H), 7.70–7.91 (m, 4H, Ar–H), 8.07–8.18 (m, 3H, Ar–H), 9.27 (s, 1H,

OH) ppm; 13C NMR (125 MHz, DMSO-d6) d: 121.4, 123.1, 123.5, 124.3, 125.3,

126.0. 126.5, 127.2, 127.8, 128.7, 129.3, 129.8, 130.3, 130.9, 131.6, 135.4, 135.6,

139.9, 141.2, 142.3, 143.2, 146.4, 147.5, 162.4, 163.5, 191.6 ppm; MS(ESI): m/z

400 (M ? H)?; Anal. Calcd for C29H17NO2: C, 84.21; H, 4.26; N, 3.51 %. Found:

C, 84.15; H, 4.21; N, 3.45 %.

4-(4-Bromophenyl)-2-naphthalen-2-yl-5H-indeno[1,2-b]pyridin-5-one (4e)

IR (KBr, cm-1): 3,051, 2,947, 2,839, 1,717, 1,607, 1,508, 1,367, 1,252, 1,157, 828,

755; 1H NMR (500 MHz, DMSO-d6) d: 7.05–7.29 (m, 8H, Ar–H), 7.54 (s, 1H, Py–

H), 7.70–7.88 (m, 4H, Ar–H), 8.07–8.16 (m, 3H, Ar–H) ppm; 13C NMR (125 MHz,

DMSO-d6) d: 120.8, 122.7, 123.3, 123.9, 125.3, 125.7. 126.5, 127.4, 128.3, 128.5,

129.0, 129.5, 130.3, 131.4, 131.9, 135.6, 136.3, 139.9, 141.2, 142.2, 142.8, 146.4,

147.2, 162.5, 164.5, 192.3 ppm; MS(ESI): m/z 462.7 (M ? H)?; Anal. Calcd for

C28H16BrNO: C, 72.74; H, 3.46; N, 3.03 %. Found: C, 72.66; H, 3.37; N, 3.04 %.

M. Ghashang et al.

123

4-(3-Methylphenyl)-2-naphthalen-2-yl-5H-indeno[1,2-b]pyridin-5-one (4f)

IR (KBr, cm-1): 3,044, 2,934, 2,828, 1,704, 1,604, 1,509, 1,364, 1,257, 1,144, 821,

754; 1H NMR (500 MHz, DMSO-d6) d: 2.21 (s, 3H, CH3), 7.27–7.53 (m, 9H, Ar–

H), 7.70 (s, 1H, Py–H), 7.80–7.94 (m, 3H, Ar–H), 8.01–8.11 (m, 3H, Ar–H) ppm;13C NMR (125 MHz, DMSO-d6) d: 17.4, 121.5, 123.4, 123.7, 123.9, 124.7, 125.6.

126.3, 127.5, 128.5, 129.4, 129.6, 130.3, 131.5, 135.0, 136.1, 139.5, 142.0, 142.8,

147.3, 148.3, 161.8, 162.9, 191.9 ppm; MS(ESI): 398 (M ? H)?; Anal. Calcd for

C29H19NO: C, 87.65; H, 4.78; N, 3.52 %. Found: C, 87.59; H, 4.74; N, 3.48 %.

4-(3-Hydroxyphenyl)-2-naphthalen-2-yl-5H-indeno[1,2-b]pyridin-5-one (4g)

IR (KBr, cm-1): 3,366, 3,045, 2,946, 2,833, 1,706, 1,604, 1,512, 1,364, 1,254,

1,151, 824, 754; 1H NMR (500 MHz, DMSO-d6) d: 7.19–7.46 (m, 8H, Ar–H), 7.68

(s, 1H, Py–H), 7.79–7.90 (m, 4H, Ar–H), 8.02–8.15 (m, 3H, Ar–H), 9.25 (s, 1H,

OH) ppm; 13C NMR (125 MHz, DMSO-d6) d: 121.4, 123.2, 123.6, 124.1, 125.0,

125.4. 126.5, 128.3, 128.7, 129.1, 129.5, 129.7, 131.3, 135.3, 135.8, 139.0, 141.6,

142.7, 146.7, 147.3, 162.3, 163.9, 191.7 ppm; MS(ESI): m/z 400 (M ? H)?; Anal.

Calcd for C29H17NO2: C, 84.21; H, 4.26; N, 3.51 %. Found: C, 84.11; H, 4.15; N,

3.49 %.

4-(4-Nitrophenyl)-2-naphthalen-2-yl-5H-indeno[1,2-b]pyridin-5-one (4h)

IR (KBr, cm-1): 3,046, 2,939, 2,836, 1,701, 1,601, 1,504, 1,361, 1,250, 1,154, 821,

755; 1H NMR (500 MHz, DMSO-d6) d: 7.20–7.42 (m, 8H, Ar–H), 7.73 (s, 1H, Py–

H), 7.87–7.99 (m, 4H, Ar–H), 8.06–8.17 (m, 3H, Ar–H) ppm; 13C NMR (125 MHz,

DMSO-d6) d: 121.4, 123.1, 123.4, 123.8, 125.2, 126.1. 126.9, 127.4, 128.4, 129.1,

129.5, 129.9, 131.4, 135.4, 135.7, 139.7, 142.4, 142.9, 147.4, 148.1, 162.0, 163.1,

191.4 ppm; MS(ESI): m/z 429 (M ? H)?; Anal. Calcd for C28H16N2O3: C, 78.50;

H, 3.74; N, 6.54 %. Found: C, 78.43; H, 3.66; N, 6.50 %.

4-(3-Fluorophenyl)-2-naphthalen-2-yl-5H-indeno[1,2-b]pyridin-5-one (4i)

IR (KBr, cm-1): 3,049, 2,942, 2,832, 1,713, 1,611 1,512, 1,362, 1,247, 1,157, 822,

759; 1H NMR (500 MHz, DMSO-d6) d: 7.09–7.30 (m, 9H, Ar–H), 7.61 (s, 1H, Py–

H), 7.70–7.85 (m, 3H, Ar–H), 8.06–8.16 (m, 3H, Ar–H) ppm; 13C NMR (125 MHz,

DMSO-d6) d: 121.4, 123.1, 123.6, 124.3, 125.0, 125.4. 126.5, 127.6, 128.1, 128.4,

128.6, 129.2, 129.5, 131.2, 131.7, 135.3, 135.6, 139.5, 142.5, 142.8, 143.1, 147.7,

148.3, 162.1, 163.8, 191.5 ppm; MS(ESI): m/z 402 (M ? H)?; Anal. Calcd for

C28H16FNO: C, 83.79; H, 3.99; N, 3.49 %. Found: C, 83.70; H, 3.95; N, 3.47 %.

4-(2-Chlorophenyl)-2-naphthalen-2-yl-5H-indeno[1,2-b]pyridin-5-one (4j)

IR (KBr, cm-1): 3,061, 2,959, 2,854, 1,711, 1,601, 1,516, 1,366, 1,255, 1,147, 817,

749; 1H NMR (500 MHz, DMSO-d6) d: 3.71 (s, 3H, OCH3), 7.22–7.49 (m, 8H, Ar–

H), 7.66 (s, 1H, Py–H), 7.76–7.88 (m, 4H, Ar–H), 8.01–8.11 (m, 3H, Ar–H) ppm;

An appropriate one-pot synthesis

123

13C NMR (125 MHz, DMSO-d6) d: 55.1, 121.1, 123.3, 123.9, 124.3, 125.3, 125.9.

126.3, 128.2, 128.8, 129.3, 129.4, 130.3, 131.3, 135.3, 135.6, 139.5, 142.1, 143.1,

147.8, 148.1, 161.4, 163.5, 192.6 ppm; MS(ESI): m/z 418.3 (M ? H)?; Anal. Calcd

for C28H16ClNO: C, 80.49; H, 3.83; N, 3.35 %. Found: C, 80.42; H, 3.75; N,

3.30 %.

4-(2-Bromophenyl)-2-naphthalen-2-yl-5H-indeno[1,2-b]pyridin-5-one (4k)

IR (KBr, cm-1): 3,053, 2,955, 2,846, 1,712, 1,605, 1,515, 1,367, 1,257, 1,145, 822,

747; 1H NMR (500 MHz, DMSO-d6) d: 7.31–7.51 (m, 8H, Ar–H), 7.66 (s, 1H, Py–

H), 7.86–7.93 (m, 4H, Ar–H), 8.04–8.17 (m, 3H, Ar–H) ppm; 13C NMR (125 MHz,

DMSO-d6) d: 121.4, 123.3, 123.7, 124.5, 125.3, 125.5. 126.3, 127.9, 128.4, 129.4,

129.6, 130.3, 131.7, 135.7, 135.9, 139.9, 141.9, 142.5, 147.3, 147.5, 162.0, 163.0,

191.6 ppm; MS(ESI): m/z 462.5 (M ? H)?; Anal. Calcd for C28H16BrNO: C,

72.74; H, 3.46; N, 3.03 %. Found: C, 72.63; H, 3.42; N, 3.00 %.

4-(4-Fluorophenyl)-2-naphthalen-2-yl-5H-indeno[1,2-b]pyridin-5-one (4l)

IR (KBr, cm-1): 3,047, 2,940, 2,831, 1,717, 1,603, 1,503, 1,367, 1,253, 1,146, 813,

755; 1H NMR (500 MHz, DMSO-d6) d: 7.14–7.40 (m, 8H, Ar–H), 7.70 (s, 1H, Py–

H), 7.80–7.92 (m, 4H, Ar–H), 8.07–8.18 (m, 3H, Ar–H) ppm; 13C NMR (125 MHz,

DMSO-d6) d: 121.3, 123.4, 123.6, 123.8, 125.3, 125.6. 126.5, 127.2, 128.0, 128.8,

129.2, 129.4, 130.2, 130.8, 131.4, 134.5, 135.5, 139.5, 141.5, 142.3, 142.6, 145.9,

147.5, 163.0, 163.8, 192.0 ppm; MS(ESI): m/z 402 (M ? H)?; Anal. Calcd for

C28H16FNO: C, 83.79; H, 3.99; N, 3.49 %. Found: C, 83.75; H, 3.98; N, 3.43 %.

Results and discussion

In order to find the most appropriate reaction conditions and evaluate the catalytic

efficiency of TUD catalyst, initially a model study to screen the best conditions was

carried out using the reaction of 4-chloro benzaldehyde (1a), 1-naphthalen-2-yl-

ethanone (2), 1,3-indandione (3) and ammonium acetate on the synthesis of 4-(4-

chlorophenyl)-2-naphthalen-2-yl-5H-indeno[1,2-b]pyridin-5-one (4a) (Table 1).

Our initial work started with screening of catalysts so as to identify optimal

reaction conditions and a suitable catalyst for the synthesis of indeno[1,2-b]pyridine

derivatives. First of all, a number of Lewis and Brønsted acid catalysts such as

FeCl3�6H2O, InCl3, LiBr, CAN, pentafluoro phenyl ammonium triflate and TUD

were screened using the model of the reaction in water as solvent (Table 1). Among

various catalysts tested, TUD was found to be the best catalyst under the reaction

conditions.

Next, the effect of the catalyst amount required for the reaction catalysis was

investigated. It was found that by decreasing the catalyst amount from 10 to

5 mol%, the yield of the reaction decreased from 94 to 76 % (Table 1, Entry 9).

When the amount of the catalyst increased from 10 to 15 mol%, there was no

prominent change in the yield (Table 1, Entry 10). The use of 10 mol% of TUD

M. Ghashang et al.

123

maintained the yield at 94 %, so this amount was sufficient to promote the reaction

yield. Using more of the catalyst improved neither the yield nor the reaction time

(Table 1, Entry10).

The efficiency of water as solvent compared to various organic solvents was also

examined (Table 2). In this study, some common protic and aprotic solvents were

tested and among them water was found to be more efficient and superior to other

solvents (Table 2, Entry 7) with respect to the reaction time and yield of the desired

5H-indeno[1,2-b]pyridin-5-one. The obtained results show that the efficiency of

TUD as catalyst in various solvents increased with increasing the polarity of the

solvent. This may be due to TUD being insoluble in almost all organic solvents, and

its solubility in most organic solvents increased with increasing the polarity of

solvents [29–31].

With these optimistic results in hand, further investigations were carried out by

using different temperatures including room temperature, 50, 60, 70, 80 and 90 �C

(Table 2, Entries 7–12). With an increase in the reaction temperature from room

temperature to 80 �C, the reaction time was decreased. The greatest yield in the

shortest reaction time was obtained in water at 80 �C (Table 2, Entry 7). The use of

water as reaction medium is not only advantageous from economical view points

but it is also beneficial from environmental and green chemistry standpoints.

Once the optimized condition for the 4-(4-chlorophenyl)-2-naphthalen-2-yl-5H-

indeno[1,2-b]pyridin-5-one synthesis was achieved, several aromatic aldehydes

possessing both electron-donating and electron-withdrawing groups were tested

under the same reaction condition (Table 3). As expected, satisfactory results were

observed, and the results are summarized in Table 3. It was shown that in general a

wide range of aldehydes could react with 1-naphthalen-2-yl-ethanone, 1,3-

indandione and ammonium acetate smoothly to give 4a–l in good to excellent

yields (Table 3, Entries 1–12). It is also notable that the electronic property of the

Table 1 Evaluation of catalytic activity of different catalysts for the condensation of 4-chlorobenzal-

dehyde, 1-naphthalen-2-yl-ethanone, 1,3-indandione and ammonium acetate in water at 80�C

Entry Catalyst (mol%) Time (h) Yield (%)a

1 FeCl3�6H2O 10 4.0 56

2 InCl3 10 4.0 64

3 LiBr 10 5.0 41

4 (NH4)2Ce(NO3)6 10 3.0 67

5 PFPAT 10 2.0 77

6 TUD 10 1.0 94

7 TUD 0 8.0 24

8 TUD 2 1.6 65

9 TUD 5 1.4 76

10 TUD 15 1.0 94

Reaction conditions: 4-chlorobenzaldehyde (1 mmol), 1-naphthalen-2-yl-ethanone (1 mmol), 1,3-indan-

dione (1 mmol) and ammonium acetate (1.3 mmol) in watera Isolated yield

An appropriate one-pot synthesis

123

aromatic ring of aldehydes has some effects on the rate of the condensation process.

The results summarized in Table 3 reveal that the reaction gave higher yields of

indeno[1,2-b]pyridines and also a shorter reaction time was needed when aromatic

aldehydes were bearing an electron-withdrawing substituent. On the other hand,

when aromatic aldehydes bearing electron-donating groups were applied, the

corresponding products with almost equally satisfactory yields were obtained but in

a slightly longer reaction time.

A possible mechanism for the formation of various 4-aryl-2-naphthalen-2-yl-5H-

indeno[1,2-b]pyridin-5-ones is shown in Scheme 2. The reaction is believed to

proceed through the formation of three intermediates: (1) the enol form of 1,3-

indandione, (2) protonated aldehyde, and (3) 1-(naphthalen-6-yl)ethenamine (b), an

enamine which resulted from the reaction of 1-naphthalen-2-yl-ethanone with

ammonium acetate. The first step of the reaction included the formation of

2-benzylidene-2H-indene-1,3-dione (a) from the condensation reaction of proton-

ated benzaldehyde with the enol form of 1,3-indandione. In the second step, the

prepared 2-benzylidene-2H-indene-1,3-dione (a) is protonate and react with

enamine (b) which undergoes the preparation of intermediate (c). The later stages

including enol-keto and imine-enamine tautomerization lead to the formation of

intermediate (d) which was transferred into the targeted molecule via cyclo-addition

and oxidation processes, respectively.

As mentioned above, aromatic aldehydes bearing electron-withdrawing groups

have lower reaction times than those with electron-donating groups. A reasonable

explanation for this result can be given by considering the nucleophilic addition to

2-benzylidene-2H-indene-1,3-dione (a) intermediate as favorable via the conjugate

addition on the a,b-unsaturated carbonyl group of this intermediate. When electron-

Table 2 Synthesis of 4-(4-chlorophenyl)-2-naphthalen-2-yl-5H-indeno[1,2-b]pyridin-5-one in the pre-

sence of TUD (10 mol%) as catalyst in different reaction conditions

Entry Solven Temperature (�C) Time (h) Yield (%)a

1 EtOH Reflux 1.5 73

2 MeOH Reflux 1.5 68

3 CH3CN Reflux 2.0 52

4 THF Reflux 2.0 44

5 1,4-Dioxane Reflux 2.0 55

6 CHCl3 Reflux 2.0 34

7 Water 80 1.0 94

8 Water RT 3.0 43

9 Water 50 2.5 67

10 Water 60 2.0 76

11 Water 70 1.5 84

12 Water 90 1.0 94

Reaction conditions: 4-chlorobenzaldehyde (1 mmol), 1-naphthalen-2-yl-ethanone (1 mmol), 1,3-indan-

dione (1 mmol) and ammonium acetate (1.3 mmol)a Isolated yield

M. Ghashang et al.

123

Table 3 TUD—catalyzed synthesis of various 4-aryl-2-naphthalen-2-yl-5H-indeno[1,2-b]pyridin-5-ones

Entry Aldehydes Product Time (h) Yield (%)a Mp (�C)

1

CHO

Cl

1aN

O

Cl

4a

1.0 94 200–202

2

CHO

CH3

1bN

O

CH3

4b

1.2 87 205–207

3

CHO

OCH3

1cN

O

OCH3

4c

1.2 88 196–198

4

CHO

OH

1dN

O

OH

4d

1.0 84 212–214

An appropriate one-pot synthesis

123

Table 3 continued

Entry Aldehydes Product Time (h) Yield (%)a Mp (�C)

5

CHO

Br

1eN

O

Br

4e

1.0 92 183–185

6

CHO

H3C

1fN

O

4f

H3C 1.2 86 195–198

7

CHO

HO

1gN

O

4g

HO 1.0 86 202–204

8

CHO

NO2

1hN

O

NO2

4h

1.0 95 224–226

9

CHO

F

1iN

O

4i

F 1.0 92 212–214

M. Ghashang et al.

123

withdrawing groups are substituted on the aromatic ring of 2-benzylidene-2H-

indene-1,3-dione (a) intermediate, the LUMO of alkene is at a lower energy than

substitution of electron-donating groups. Thus, the rate of 1,4-nucleophilic addition

reaction increased with the substitution of electron-withdrawing groups on the

aromatic ring [32].

Next, we checked the recycling ability of the catalyst for the synthesis of 4-(4-

chlorophenyl)-2-naphthalen-2-yl-5H-indeno[1,2-b]pyridin-5-one in the presence of

a catalytic amount of TUD (10 mol%) in water. After completion of the reaction,

the reaction mixture was diluted with water (10 mL) and extracted with ethyl

acetate (3 9 10 mL). After that, the water was removed and the catalyst was

washed with ethyl acetate. The recycling ability of the TUD was tested for four runs,

Table 3 continued

Entry Aldehydes Product Time (h) Yield (%)a Mp (�C)

10

CHO

Cl

1jN

O

4j

Cl

1.2 89 192–194

11

CHO

Br

1kN

O

4k

Br

1.2 87 205–206

12

CHO

F

1lN

O

F

4l

1.0 93 234–236

Reaction conditions: aryl aldehydes (1 mmol), 1-naphthalen-2-yl-ethanone (1 mmol), 1,3-indandione

(1 mmol) and ammonium acetate (1.3 mmol) under heating at 80 �C in the presence of TUD in watera Isolated yield

An appropriate one-pot synthesis

123

providing 94–88 % of the desired product yield in a similar reaction time. The

results of recycling experiments are given in Fig. 1. These results established the

efficient recycling of the TUD catalyst with consistent activity.

O NH4OAc AcOH + H2O

N

O

TUD

-H2

NH

NH

O

NH2

b

Oxidation

4

H

O

O

O

O

O

TUD

HO

O

TUD H

OH

HO

O

+H

OH

-H2O

a

O

O

TUD

O

O

H

b

HO

O

H2N

c

HO

O

H2NO

O

H2N

d

-H2O

Scheme 2 Probable mechanism for the TUD catalysed one-pot synthesis of various 4-aryl-2-naphthalen-2-yl-5H-indeno[1,2-b]pyridin-5-one derivatives

M. Ghashang et al.

123

Conclusion

In summary, we have successfully developed efficient synthesis of various 4-aryl-2-

naphthalen-2-yl-5H-indeno[1,2-b]pyridin-5-ones from the one-pot condensation of

aryl aldehydes, 1-naphthalen-2-yl-ethanone, 1,3-indandione and NH4OAc in the

presence of a catalytic amount of TUD at 80 �C in water. The present method has

many obvious advantages compared to those reported in the previous literature,

including short reaction time, ease of product isolation and purification, high

chemoselectivity, no side reaction and eco-friendly nature. The recovered TUD can

be reusable.

Acknowledgment The author Mansoor is grateful to the Management of C. Abdul Hakeem College,

Melvisharam—632 509 (T.N), India for the facilities and support.

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