An easy and efficient protocol for the condensation reaction of isatin and N-substituted isatins with 1,2-diaminobenzene using low cost reusable clay catalyst

Article abstract of DOI:10.1515/hc-2013-0156

A green procedure was developed for the condensation of isatin and N-substituted isatins with 1,2-diaminobenzene by using reusable bentonite clay in EtOH/H₂O solvent system, under microwave irradiation. This eco-friendly synthesis is characterized by high yields and short reaction times. The catalyst is easily recycled.

Full text of DOI:10.1515/hc-2013-0156

ꢁꢁꢁꢂ
ꢀHeterocycl. Commun. 2014; 20(1): 37–39
DOI 10.1515/hc-2013-0156ꢀ
SAhnivameaBasjpyai,aSunnddaraemfSfiincgihe* anndtVpanrdoantaoSrcivoasltafvoa r the condensation
reaction of isatin and N-substituted isatins with
1,2-diaminobenzene using low cost reusable clay
catalyst
Abstract: A green procedure was developed for the
condensation of isatin and N-substituted isatins with
Results and discussion
1,2-diaminobenzene by using reusable bentonite clay
We describe herein a simple and efficient protocol for the
in EtOH/H2O solvent system, under microwave irradia-
condensation reaction of isatin and N-substituted isatins
tion. This eco-friendly synthesis is characterized by high
with 1,2-diaminobenzene using bentonite clay catalyst in
yields and short reaction times. The catalyst is easily
EtOH/H2O solvent system under conventional and micro-
recycled.
wave irradiation methods. Spiroindoles and quinoxaline
derivatives 2a–f were synthesized by condensation of 1a–f
Keywords: bentonite clay; microwave irradiation;
[15] with equimolar amount of 2 using bentonite clay in
N-substituted isatins; quinoxaline derivatives; spiroindoles.
EtOH/H2O solvent system, under conventional and micro-
wave irradiation methods (Scheme 1).
*Corresponding author: Sundaram Singh, Department of Chemistry,
Indian Institute of Technology, Banaras Hindu University, Varanasi
221005, India, e-mail: sundaram.apc@itbhu.ac.in
Shivam Bajpai and Vandana Srivastava: Department of Chemistry,
Indian Institute of Technology, Banaras Hindu University, Varanasi
221005, India
To optimize the conditions, various parameters such
as catalyst amount (10–40 mol%), solvents and solvent
systems were investigated in detail by taking condensa-
tion reaction between 1a and 2 as a reference reaction.
The best result was obtained for the reaction conducted in
EtOH/H2O (3:1) in the presence of 20 mol% bentonite clay.
Under the optimized conditions, compounds 2a–f
were synthesized in yields of 74–81% by conventional
method after 2–3 h. The use of microwave irradiation
resulted in higher yields of 86–94% and shortening of the
Introduction
One of the major current challenges is to develop syn- reaction time to 3–5 min. The reaction of 1a with 2 and
thetic methods that are less polluting. In particular, analogous reactions have been studied previously [16–19].
the field of heterogeneous catalysis has captivated the Niume et al. [16] have reported that the reaction between
interest of researchers due to an increasing demand for isatin and 1,2-diaminobenzene is solvent-dependent.
more environmentally acceptable processes in the chemi- Recently, Alsubari et al. [19] have also reported that treat-
cal industry [1, 2]. In recent years, the use of solid acid ment of N-substituted isatin with 1,2-diaminobenzene
catalyst such as clays, ion-exchange resins and zeolites produces a quinoxaline product. In our hands, the reac-
has received considerable attention in different areas of tion of 1a with 2 gave a spiroindole derivative 2a as sole
organic synthesis [3–6]. The chemistry of spiroindoles product by using bentonite clay in EtOH/H2O solvent
and quinoxalines has received considerable attention system, under both conventional and microwave irradia-
due to their synthetic and biological importance [7, 8]. tion methods. When 1b–d was allowed to react with 2, the
Such compounds often exhibit potent antiviral and anti- sole product formed was quinoxaline derivatives 2b–d.
bacterial [9–12] properties. Although clay has been used However, when 1e or 1f was treated with 2, the expected
as a catalyst in many reactions [13, 14], there is no report quinoxaline product was not formed. Instead, the spiroin-
of the use of bentonite clay as a catalyst for condensa- dole derivatives 2e and 2f were the sole products. The
tion reaction of isatin and N-substituted isatin derivatives structures of all isolated products were fully confirmed by
with 1,2-diaminobenzene.
elemental and spectroscopic analysis.
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38ꢀ
ꢀS. Bajpai et al.: Clay catalyzed condensation of isatins with 1,2-diaminobenzene
O
H
N
HN
1a
N
H
2a
H2N
R
O
N
N
H2N
1b-d
1e,f
O
N
Bentonite
EtOH/H2O, 70°C
Conventional: 2-3 h
Microwave: 3-5 min
N
R
2b-d
1a-f
O
H
N
R
N
N
H
1a 2a
1b 2b
,
,
: R = H
: R = Et
1c, 2c: R = CH2COOEt
2e f
-
1d 2d
,
: R = CH2CH2CH2CH2Br
1e, 2e: R = CH2N(Ph)2
1f 2f
,
: R = CH2N(Et)2
Scheme 1ꢀ
In this reaction, bentonite clay can be reused several
times without any appreciable loss in activity. For
example, in the reaction of 1a with 2 no significant loss of
product yield (92–88%) was observed when bentonite clay
was used after four times of recycling.
General procedure for the synthesis
of compounds 2a–e
Conventional methodꢀ1,2-Diaminobenzene (0.001 mol) was added
to a mixture of isatin or N-substituted isatins (1a–f, 0.001 mol), ben-
tonite clay (20 mol%) and EtOH/H2O (v/v, 3:1, 20 mL). The reaction
mixture was stirred at 70°C for 2–3 h. The progress of the reaction
was monitored by TLC. The catalyst was filtered, washed with ethyl
acetate and dried. The filtrate was concentrated under reduced pres-
sure, and the residue was crystallized from ethanol.
Conclusion
The advantages of the developed method are mild reac-
tion conditions, simple isolation procedures, high yields,
short reaction times and the reusability of the bentonite
clay catalyst.
Microwave irradiation methodꢀThe mixture, prepared as
described above, was stirred at 70°C for 3–5 min under microwave
irradiation of 500 W. Workup was conducted as described above.
1,3-Dihydrospiro[benzo[d]imidazole-2,3′-indolin]-2′-one
(2a)ꢀBrown-yellow solid; yield 92%; mp 232°C; 1H NMR (DMSO-d6): δ
12.02 (s, 1H, NH), 8.35–6.53 (m, 8H, Ar-H), 6.43 [s, 1H (D2O exchange-
able), NH]: IR: νmax 3192, 3090, 3019, 1703, 1614, 1598, 1484, 1339, 718,
671 cm-1. Anal. Calcd for C14H11N3O (237.26): C, 70.87; H, 4.67; N, 17.71; O,
6.74. Found: C, 70.85; H, 4.68; N, 17.72; O, 6.74.
Experimental
General
6-Ethyl-6H-indolo[2,3-b]quinoxaline (2b)ꢀYellow solid; yield
1
89%; mp 180°C; H NMR (CDCl3): δ 8.49–7.35 (m, 8H, Ar-H), 4.56 (q,
All chemicals were procured from Aldrich, USA and E. Merck, Ger-
many and used as such. TLC was carried out on silica gel (HF254, 200
mesh) eluting with ethyl acetate/chloroform (11:9). IR spectra were
recorded in KBr pellets on a PerkinElmer FT/IR spectrometer. NMR
spectra were run on a JEOL AL 300 spectrometer operating at 300
MHz. Elemental analysis was performed on an Exeter Analytical
2H, J ꢀ= ꢀ 7 Hz, CH2), 1.52 (t, 3H, J ꢀ= ꢀ 7 Hz, CH3); IR: νmax 2962, 2853, 1660,
1611, 1567, 1482, 1427, 1378, 1331, 757, 738 cm-1. Anal. Calcd for C16H13N3
(247.29): C, 77.71; H, 5.30; N, 16.99. Found: C, 77.73; H, 5.29; N, 16.98.
Ethyl 2-(6H-indolo[2,3-b]quinoxaline-6-yl)acetate (2c)ꢀYellow
1
Model CE-440 CHN analyzer. Melting points were measured in open solid; yield 91%; mp 160°C; H NMR (CDCl3): δ 8.50–7.34 (m, 8H,
capillaries and are uncorrected. The microwave assisted reactions Ar-H), 5.24 (s, 2H, CH2), 4.24 (q, 2H, J ꢀ= ꢀ 7 Hz, CH2), 1.28 (t, 3H, J ꢀ= ꢀ 7 Hz,
were carried out in a MAS-II, Microwave Synthesis System manufac- CH3): IR: νmax 2976, 2927, 1734, 1663, 1606, 1565, 1474, 1375, 1203, 760,
tured by Sineo Microwave Chemistry Technology, Ltd, having an out- 743 cm-1. Anal. Calcd for C18H15N3O2 (305.33): C, 70.81; H, 4.95; N, 13.76;
put energy range of 0–1000 W.
O, 10.48. Found: C, 70.80; H, 4.96; N, 13.75; O, 10.49.
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S. Bajpai et al.: Clay catalyzed condensation of isatins with 1,2-diaminobenzeneꢀ
ꢀ39
6-(4-Bromobutyl)-6H-indolo[2,3-b]quinoxaline
(2d)ꢀYellow 1′-[(Diethylamino)methyl]-1,3-dihydrospiro[benzo[d]imidazole-
1
1
solid; yield 94%; mp 184°C; H NMR (CDCl3): δ 8.53–7.38 (m, 8H, 2,3′-indolin]-2′-one (2f)ꢀYellow solid; yield 86%; mp 246°C; H
Ar-H), 4.42 (t, 2H, J ꢀ= ꢀ 7 Hz, CH2), 3.38 (t, 2H, J ꢀ= ꢀ 7 Hz, CH2), 2.02 (m, NMR (DMSO-d6) δ: 8.07–6.53 (m, 8H, Ar-H), 6.42 [s, (D2O exchange-
2H, CH2), 1.82 (m, 2H, CH2): IR: νmax 3050, 2930, 1660, 1493, 1485, able), NH], 4.72 (s, 2H, CH2), 2.89 (q, 4H, J ꢀ= ꢀ 7 Hz, CH2), 1.63 (t, 6H,
1450, 1400, 1330, 1192, 1130, 751, 741 cm-1. Anal. Calcd for C18H16BrN3 J ꢀ= ꢀ 7 Hz CH3): IR: νmax 3384, 2850, 1703, 1613, 1598, 1483, 1322, 759, 743
(354.24): C, 61.03; H, 4.55; Br, 22.56; N, 11.86. Found: C, 61.01; H, 4.57; cm-1. Anal. Calcd for C19H22N4O (322.40): C, 70.78; H, 6.88; N, 17.38; O,
Br, 22.57; N, 11.85.
4.96. Found: C, 70.75; H, 6.89; N, 17.41; O, 4.95.
1′-[(Diphenylamino)methyl]-1,3-dihydrospiro[benzo[d]
Acknowledgment: We thank the University Grant Com-
imidazole-2,3′-indolin]-2one (2e)ꢀBrown solid; yield 88%; mp
1
228°C; H NMR (DMSO-d6) δ: 8.35–6.56 (m, 18H, Ar-H), 6.45 [s, (D2O mission, New Delhi and Banaras Hindu University, Vara-
exchangeable), NH], 5.21 (s, 2H, CH2): IR: νmax 3090, 2980, 2850, 1703,
nasi for financial support of this work.
1614, 1567, 1483, 1350, 744, 752 cm-1. Anal. Calcd for C27H22N4O (418.49):
C, 77.49; H, 5.30; N, 13.39; O, 3.82. Found: C, 77.50; H, 5.30; N, 13.38; Received September 14, 2013; accepted December 9, 2013; previ-
O, 3.82.
ously published online January 11, 2014
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