A greener, facile and scalable synthesis of indole derivatives in water: Reactions of indole-2,3-diones with 1,2-difunctionalized benzene

Article abstract of DOI:10.1016/j.tetlet.2012.09.013

An efficient, facile and greener protocol for the synthesis of indole derivatives viz., 3'H-spiro[indole- 3,2'-[1,3]benzothiazole]-2(1H)-ones, 6H-indolo[2,3-b]quinoxalines and 3-(2-hydroxy-phenylimino)- 1,3-dihydro-indol-2- ones, by the reactions of indol

Full text of DOI:10.1016/j.tetlet.2012.09.013

Tetrahedron Letters 53 (2012) 6236–6240
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Tetrahedron Letters
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A greener, facile and scalable synthesis of indole derivatives in water:
reactions of indole-2,3-diones with 1,2-difunctionalized benzene
⇑
Renuka Jain , Kanti Sharma, Deepak Kumar
Department of Chemistry, University of Rajasthan, Jaipur 302 004, India
a r t i c l e i n f o
a b s t r a c t
An efficient, facile and greener protocol for the synthesis of indole derivatives viz., 30H-spiro[indole-
3,20-[1,3]benzothiazole]-2(1H)-ones, 6H-indolo[2,3-b]quinoxalines and 3-(2-hydroxy-phenylimino)-
1,3-dihydro-indol-2-ones, by the reactions of indole-2,3-diones with 1,2-difunctionalized benzene using
tetrabutylammonium bromide (TBAB), as a surfactant under aqueous micellar media is described. This
methodology has advantages of simple handling, mild reaction conditions and high yields of products
in shorter reaction time as well as environmentally benign synthesis.
Article history:
Received 23 July 2012
Revised 3 September 2012
Accepted 5 September 2012
Available online 13 September 2012
Keywords:
Indole-2,3-diones
Ó 2012 Elsevier Ltd. All rights reserved.
1,2-Difunctionalized benzene
Tetrabutylammonium bromide
Aqueous micellar media
Eco-friendly synthesis
In recent years, the main aims of green chemistry are the devel-
opment of cleaner and more benign chemical processes by replace-
ment of volatile and hazardous reagents and solvents with
environmentally benign materials and thus increase of process
selectivity.1,2 Organic synthesis in water is both environmentally
and economically benign because of the cheap, non-inflammable,
nontoxic, safe to use and unique physical and chemical properties
such as the network of hydrogen bond, the large surface tension,
high specific heat capacity and high polarity which often increases
its reactivity and selectivity that cannot be obtained in organic sol-
vents.1c,3 Further, due to poor solubility of organic molecules in
water, it provides an easy approach for the separation of hazardous
organic reagents, by-products and catalysts from the aqueous
phase.4 Therefore, in the past decade, aqueous-mediated reactions
have been extensively pursued due to their efficient, atom-econ-
omy and green credentials.5
Recently, surfactants (surface-active reagents) have attracted
considerable interest in organic synthesis because of their high cat-
alytic activity and benign character in the context of green chem-
istry. Introduction of surfactants in aqueous medium has been
proved to increase the reactivity of aqueous mediated reactions
via the formation of vesicular cavities or micelles with hydropho-
bic core and hydrophilic corona at ambient conditions. The cata-
lytic use of micellar surfactants in water is widespread and has
been studied in detail for a number of different reactions in aque-
ous medium which provides an alternative synthetic approach un-
der aqueous conditions.6
Indole-2,3-dione commonly known as isatin and its derivatives
possess interesting biological activities and are widely used as a
precursor for many natural products.7 Furthermore, compounds
possessing this heterocyclic nucleus have been isolated from plants
also.8 The heterocyclic spiro-oxindole framework is a privileged
structure motif that forms the core of a large family of natural
products with interesting biological and structural properties
(Fig. 1). Spiro-oxindole ring system and its derivatives exhibit
numerous types of biological activities such as antimicrobial, anti-
tumor, antileukemic and anticonvulsant as well as found to be po-
tent nonpeptide inhibitors of the p53-MDM2 interaction.9 These
have also been reported to act as aldose reductase, poliovirus
and rhinovirus 3C-proteinase inhibitors.10
A published report’s survey revealed that the synthesis of indole
derivatives by the reactions of indole-2,3-diones with 1,2-difunc-
tionalized benzene has been carried out using different solvents
and catalysts.11 However, in these reported methods, most of the
synthetic approaches are associated with harsh reaction condi-
tions, using environmentally black-listed solvents, prolonged reac-
tion time and tedious isolation procedure with poor yields.
Therefore, it appeared to be of interest to develop eco-friendly, fac-
ile and more practical procedure for the synthesis of these impor-
tant heterocyclic derivatives.
Considering the significance of surfactants and in our continu-
ous ongoing efforts to develop new efficient protocol for the syn-
thesis of bioactive heterocycles employing green tools from
readily available building blocks,12 herein we report for the first
⇑
Corresponding author. Tel.: +91 141 2742048.
E-mail address: profrjain@rediffmail.com (R. Jain).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.09.013

R. Jain et al. / Tetrahedron Letters 53 (2012) 6236–6240
6237
amounts of the catalyst studied, 15 mol % of TBAB was found to
be the best at 60 °C temperature, in aqueous condition.
O
O
O
H
N
SCH3
N
HN
N
It was observed that on introduction of TBAB followed by stir-
ring, the initially floating reactants in the mixture converted to a
yellowish-brown turbid emulsion (Fig. 2a), which implies that
there was the formation of micelle like colloidal aggregates. In-
deed, the light microscopic observation of the emulsion dispersion
formed from indole-2,3-dione, 2-aminothiophenol and TBAB in
distilled water revealed that spherical particles were formed
(Fig. 2b).13 It is assumed that most of the organic substrates are
concentrated in the spherical particles, which act as a hydrophobic
reaction site and result in the rapid reaction in water. The catalytic
effect of micellar TBAB in these reactions may be explained as fol-
lows. Indole-2,3-diones as well as 1,2-difunctionalized benzene
molecules are hydrophobic in aqueous medium. In the micellar
solution, the organic substrates which are hydrophobic, escape
from water molecule towards the hydrophobic core of micelle
droplets where the reaction occurred more easily. The hydrophobic
interior of the micelles rapidly excludes the water molecules gen-
erated during the reaction, thus shifting the equilibrium towards
the product side.14 The above explanation is schematically pre-
sented in Figure 3.
S
O
H
MeO
N
H
Spirotryprostatin A
Spirobrassinin
NH
N
Bu-i
O
O
O
N
H
N
H
OH
Elacomine
Horsfiline
Figure 1. Examples of oxindole moiety containing natural products.
The synthesis of compounds 4a–c have been performed by tak-
time, a green, efficient and new procedure for the synthesis of in-
dole derivatives in aqueous micellar media using tetrabutylammo-
nium bromide, as a surfactant in water.
ing indole-2,3-diones 1a–c (1.0 mmol), 2-aminothiophenol
2
(1.0 mmol) and tetrabutylammonium bromide (15 mol %) in dis-
tilled water. The reaction has been carried out by stirring the reac-
tion mixture at 60 2 °C until completion of the reaction as
evidenced by TLC (Scheme 1 and Table 2).15
Initially, the b-carbonyl group of 1 reacts with the amino group
of 2 leading to the formation of intermediate 3, this is followed by
the nucleophillic attack of the thiol group (presence of more acidic
hydrogen on thiol group) on the b-carbon leading to the formation
of 4 by the removal of a water molecule.
The isolated products 4 were characterized on the basis of their
IR, 1H and 13C NMR spectroscopy, mass spectrometry and elemen-
tal analysis. The IR spectrum of 4b showed absorptions at 3320 and
1712 cmꢀ1 indicative of the –NH and carbonyl functionality of ben-
zothiazole moiety and oxindole ring, respectively. The 1H NMR
spectrum of 4b exhibited two sharp singlets arising from the pro-
ton of –NCH3 of oxindole (d 3.20 ppm) and –NH group of benzothi-
azole (d 7.26 ppm) along with characteristic signals with
appropriate chemical shifts and coupling constants for the eight
H-atoms of the two aromatic moieties. In the 13C NMR spectrum
the signal at d 74.0 ppm indicates the presence of a quaternary car-
bon atom with spiro linkage. The carbon atoms of the –NCH3 and
carbonyl group of the oxindole ring resonated at d 26.5 and
175.2 ppm, respectively. The mass spectrum of 4b displayed a
The choice of an appropriate reaction medium is of essential
importance for a successful synthesis. In our initial investigation,
the reaction of indole-2,3-dione 1a, and 2-aminothiophenol 2, as
a model substrate was investigated to establish the feasibility of
the strategy and optimize the reaction conditions. Various solvents
such as methanol, ethanol (neutral/acidic) as well as water with/
without surfactant were screened and optimized. The best results
that is excellent yields in shorter reaction time were obtained in
aqueous medium with surfactants where there was no require-
ment for a further purification process like column chromatogra-
phy. We have carried out the reactions at different temperatures
using different concentrations of the surfactant and the data are
presented in Table 1, from which it is clear that the rate of reaction
increased continuously with increase of the catalyst concentration
upto 15 mol % without any considerable difference on a further in-
crease of the catalyst concentration. It was observed that the con-
centration of the catalyst plays a significant role in controlling the
rate of the reaction and it was concluded that among the various
Table 1
Synthesis of 4a under different reaction conditionsa
Entry Solvent
Temperature (°C) Reaction time (h) Yieldb (%)
1
2
3
4
5
6
7
8
MeOH
EtOH (neutral) Reflux
EtOH (acidic)
Water
Reflux
4
5
4
3
58
56
58
72
84
84
81
80
77
81
89
90
Reflux
Reflux
RT
60
80
100
Reflux
60
60
60
Water/TBABc
Water/TBABc
Water/TBABc
Water/TBABc
Water/TBABc
Water/TBABd
Water/TBABe
Water/TBABf
6
0.5
0.5
0.5
0.5
0.5
0.5
0.5
9
10
11
12
a
Reaction conditions: 1.0 mmol of indole-2,3-dione 1a and o-aminothiophenol 2
was used.
b
Isolated yield.
c
d
e
f
TBAB (10 mol %).
TBAB (5 mol %).
TBAB (15 mol %).
TBAB (20 mol %).
Figure 2. (a) Reaction mixture of the indole-2,3-dione (1a), o-aminothiophenol (2)
and TBAB in distilled water. (b) Optical micrograph of the reaction mixture (scale
bar = 25 lm).

6238
R. Jain et al. / Tetrahedron Letters 53 (2012) 6236–6240
O
S
O
N
H
NH
+
O
N
H
H2N
HS
+
H2O
Hydrophobic interior
Hydrophilic exterior
: TBAB
Figure 3. Micelles-promoted green synthesis of 30H-Spiro[indole-3,20-[1,3]benzothiazole]-2(1H)-one.
S
H
S
TBAB (15 mol%)
Water, 60 °C
HO
O
H N
2
-H2O
NH
N
H
+
O
O
O
N
R
N
R
HS
N
R
3a-c
4a-c
1a-c
2
R = H, CH3, CH2Ph
Scheme 1. Synthesis of 30H-spiro[indole-3,20-[1,3]benzothiazole]-2(1H)-ones 4a–c.
Table 2
Table 3
Synthesis of 30H-spiro[indole-3,20-[1,3]benzothiazole]-2(1H)-one derivatives 4a–ca
Synthesis of 6H-indolo[2,3-b]quinoxaline derivatives 7a–ca
Entry Product
R
Temperature
(°C)
Reaction time
(min)
Yieldb
(%)
Entry Product
R
Temperature
(°C)
Reaction time
(min)
Yieldb
(%)
1
2
3
4a
4b
4c
H
CH3
CH2Ph 60
60
60
30
35
50
89
85
83
1
2
3
7a
7b
7c
H
CH3
CH2Ph 60
60
60
50
40
50
85
83
83
a
a
Reaction conditions: 1.0 mmol of indole-2,3-diones 1a–c and o-aminothio-
Reaction conditions: 1.0 mmol of indole-2,3-diones 1a–c and o-phenylenedi-
phenol 2, TBAB (15 mol %) and distilled water (5.0 mL) was used.
amine 5, TBAB (15 mol %) and distilled water (5.0 mL) was used.
b
b
Isolated yield.
Isolated yield.
molecular ion peak (M+) at m/z 268.3, which is 18 mass units (H2O)
lower than that of a 1:1 adduct of 1-methyl-indole-2,3-dione and
o-aminothiophenol which further supported the formation of cyc-
loadduct 4b.15
TBAB (15 mol%)
H
HO
N
N
O
N
H N
Water, 60 °C
2
-2H2O
+
N
R
O
N
R
H N
2
N
R
O
H N
2
7a-c
5
6a-c
Scheme 2. Synthesis of 6H-indolo[2,3-b]quinoxalines 7a–c.

R. Jain et al. / Tetrahedron Letters 53 (2012) 6236–6240
6239
H
TBAB (15 mol%)
Water, 60 °C
HO
N
O
O
H2N
HO
N
-H2O
+
O
N
R
N
R
N
R
O
HO
HO
8
10a-c
9a-c
Scheme 3. Synthesis of 3-(2-hydroxy-phenylimino)-1,3-dihydro-indol-2-ones 10a–c.
adduct of the reactant and further confirmed the formation of
product 7b.17
Table 4
Synthesis of 3-(2-hydroxy-phenylimino)-1,3-dihydro-indol-2-one derivatives 10a–ca
On a similar protocol, we next investigated other 1,2-difunc-
tionalized benzene, o-aminophenol 8 where interesting results
were obtained. In this case there was the formation of Schiff’s
bases, 3-(2-hydroxy-phenylimino)-1,3-dihydro-indol-2-ones 10a–
c only in excellent yields instead of spiro or other condensed prod-
ucts (Scheme 3 and Table 4). The formation of the products 10a–c
was explained as amino group of 8 reacts with b-carbonyl of
indole-2,3-diones affording intermediates 9a–c, which on the
removal of one molecule of water gave 3-(2-hydroxy-phenylimi-
no)-1,3-dihydro-indol-2-ones. On the other hand the formation
of spiro derivatives was ruled out due to the presence of less acidic
hydrogen of the hydroxyl group and also the possibility of the
condensed product was ruled out due to the presence of –OH
group in the product.
The chemical structure of the products was proven on the basis
of their spectral data. The IR spectrum of the 10a showed a broad
signal at 3100–3295 cmꢀ1 due to –NH and –OH along with signals
at 1722 and 1618 cmꢀ1 due to C@O and C@N groups, respectively.
The absorption band at 1290 cmꢀ1 is attributed to the phenolic C–
O stretching vibration.19
Entry Product
R
Temperature
(°C)
Reaction time
(min)
Yieldb
(%)
1
2
3
10a
10b
10c
H
CH3
CH2Ph 60
60
60
45
40
40
86
84
85
a
Reaction conditions: 1.0 mmol of indole-2,3-diones 1a–c and o-aminophenol 8,
TBAB (15 mol %) and distilled water (5.0 mL) was used.
b
Isolated yield.
TBAB(15mol%)
Water, 60 °C
O
HO
HO
No reaction
+
O
N
R
11
Scheme 4.
Encouraged by this success, we have extended this protocol to
another 1,2-difunctionalized benzene which is o-phenylenedi-
amine 5 under similar conditions as optimized (Scheme 2 and
Table 3). Several investigations of the reactions between
indole-2,3-diones and o-phenylenediamine in various solvents
have been carried out and found that the solvent used in the reac-
tion can shift the reaction towards the formation of different prod-
ucts.7,11a,16 When this reaction was performed in optimized
condition, we found that there was the formation of quinoxaline
derivatives 7a–c instead of spiro cycloadduct which was confirmed
by the 13C NMR spectrum in which no signals due to C@O of oxin-
dole ring and spiro carbon were observed while a peak at
1620 cmꢀ1 due to the presence of C@N appeared.17
Further, when this methodology was applied for 1,2-dihydroxy
benzene 11, the reaction was not successful in the all optimized
conditions (Scheme 4).
In conclusion, an efficient, facile and straightforward green pro-
tocol for the synthesis of indole derivatives has been developed by
using TBAB, as a surfactant in aqueous medium for the first time.
The reactions of indole-2,3-diones with various 1,2-difunctional-
ized benzene viz., o-aminothiophenol, o-phenylenediamine and
o-aminophenol afford 30H-spiro[indole-3,20-[1,3]benzothiazole]-
2(1H)-ones, 6H-indolo[2,3-b]quinoxalines and 3-(2-hydroxy-phe-
nylimino)-1,3-dihydro-indol-2-ones, respectively while a reaction
does not take place with 1,2-dihydroxy benzene.
It is well known that ammonia reacts with the b-carbonyl of in-
dole-2,3-dione to give the adduct at lower temperatures.18 The
analogous intermediates 6a–c would give a preferable explanation
of the formation of 7a–c. The reaction of the amino group with the
Acknowledgements
Authors are grateful to CSIR and UGC, New Delhi, India for
financial assistance.
a-carbonyl of the 6a–c, followed by the removal of two molecule of
water would give 7a–c.
References and notes
The structure of products 7 was characterized on the basis of
their spectral and elemental analyses. The IR spectrum of the prod-
uct 7b showed a peak at 1620 cmꢀ1 due to C@N group in the tetra-
cyclic ring system. In the IR spectrum, the disappearance of two
C@O of the oxindole ring along with the appearance of a signal
due to C@N further proved the formation of quinoxaline deriva-
tives instead of a spiro cycloadduct. In the 1H NMR spectrum, H-
atoms of the –NCH3 group of the oxindole ring appeared at d
2.94 ppm as a singlet along with characteristic signals with appro-
priate chemical shift and coupling constant for the eight protons of
the two aromatic moieties. In the 13C NMR, the C-atom of –NCH3 of
oxindole ring resonated at d 30.0 ppm along with aromatic signals.
In the mass spectrum, molecular ion peak (M+) appeared at m/z
233.2, which is 36 mass units (2 ꢁ H2O) lower than that of a 1:1
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30H-Spiro[indole-3,2’-[1,3]benzothiazole]-2(1H)-one 4a (Table 2, entry 1): Light
yellow solid; mp 220–222 °C; IR (KBr, cmꢀ1): 3310, 3195, 1705, 1465, 758; 1
H
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NMR (300 MHz, DMSO-d6): d 6.65–6.74 (m, 2H, Ar-H), 6.88 (t, 1H, J = 7.8 Hz,
Ar-H), 6.94 (d, 1H, J = 7.2 Hz, Ar-H), 7.03 (t, 1H, J = 7.2 Hz, Ar-H), 7.22–7.30 (m,
1H, Ar-H), 7.49 (d, 1H, J = 7.2 Hz, Ar-H), 7.54 (s, 1H, NH, D2O exchangeable),
7.57 (d, 1H, J = 6.9 Hz, Ar-H), 9.96 (s, 1H, NH, D2O exchangeable); 13C NMR
(75 MHz, DMSO-d6): 73.9, 109.0, 109.7, 119.2, 120.5, 122.1, 124.3, 124.8, 125.0,
129.5, 129.6, 140.3, 145.7, 176.3; MS (m/z): 254.3; Anal. Calcd for C14H10N2OS:
C, 66.06; H, 3.93; N, 11.01. Found; C, 66.18; H, 3.85; N, 11.12.
1-Methyl-30H-spiro[indole-3,20-[1,3]benzothiazole]-2(1H)-one 4b (Table 2, entry
2): Light yellow solid; mp 162–164 °C; IR (KBr, cmꢀ1): 3320, 1712, 1470, 755;
1H NMR (300 MHz, DMSO-d6): d 3.20 (s, 3H, N-CH3), 6.70 (d, 1H, J = 7.8, Ar-H),
6.81 (t, 1H, J = 7.8 Hz, Ar-H), 6.82–6.94 (m, 1H, Ar-H), 6.99 (d, 1H, J = 7.2 Hz, Ar-
H), 7.02 (dd, 1H, J = 7.6, 1.2 Hz, Ar-H), 7.12 (d, 1H, J = 7.8 Hz, Ar-H), 7.26 (s, 1H,
NH, D2O exchangeable), 7.36 (d, 1H, J = 6.9 Hz, Ar-H), 7.61 (t, 1H, J = 7.8 Hz, Ar-
H); 13C NMR (75 MHz, DMSO-d6): 26.5, 74.0, 108.5, 110.9, 121.4, 121.6, 123.6,
123.7, 125.1, 125.9, 129.7, 130.7, 142.4, 145.3, 175.2; MS (m/z): 268.3; Anal.
Calcd for C15H12N2OS: C, 67.08; H, 4.47; N, 10.43. Found; C, 66.97; H, 4.58; N,
10.49.
16. (a) Popp, F. D. Adv. Heterocycl. Chem. 1975, 18, 1; (b) Bergman, J.; Engqvist, R.;
Stalhandske, C.; Wallberg, H. Tetrahedron 2003, 59, 1033.
10. Skiles, J. W.; Mc Neil, D. Tetrahedron Lett. 1990, 31, 7277.
17. General procedure for synthesis of 7a: A mixture of indole-2,3-dione 1a
11. (a) Popp, F. D. J. Heterocycl. Chem. 1969, 6, 125; (b) Karali, N.; Guzel, O.; Ozsoy,
N.; Ozbey, S.; Salman, A. Eur. J. Med. Chem. 2010, 45, 1068; (c) Alam, Y. A.;
Nawwar, G. A. M. Heteroatom Chem. 2002, 13, 207; (d) Dowlatabadi, R.; Khalaj,
A.; Rahimian, S.; Montazeri, M.; Amini, M.; Shahverdi, A.; Mahjub, E. Synth.
Commun. 2011, 41, 1650.
12. (a) Jain, R.; Sharma, K.; Kumar, D. Tetrahedron lett. 2012, 53, 1993; (b) Jain, R.;
Sharma, K.; Kumar, D. Helv. Chim. Acta 2012. http://dx.doi.org/10.1002/
hlca.2012,00,168; (c) Jain, R.; Sharma, K.; Kumar, D. J. Heterocycl. Chem. 2011.
http://dx.doi.org/10.1002/jhet.1071; (d) Jain, R.; Yadav, T.; Kumar, M.; Yadav,
A. K. Synth. Commun. 2011, 41, 1889; (e) Jain, R.; Yadav, T.; Kumar, M.; Yadav, A.
K. J. Heterocycl. Chem. 2010, 47, 603; (f) Yadav, A. K.; Kumar, M.; Yadav, T.; Jain,
R. Synlett 2010, 5, 712; (g) Yadav, A. K.; Kumar, M.; Yadav, T.; Jain, R.
Tetrahedron Lett. 2009, 50, 5031; (h) Yadav, A. K.; Manju, M.; Kumar, M.; Yadav,
T.; Jain, R. Tetrahedron Lett. 2008, 49, 5724.
13. (a) Watanabe, Y.; Sawada, K.; Hayashi, M. Green Chem. 2010, 12, 384; (b)
Shinde, P. V.; Kategaonkar, A. H.; Shingate, B. B.; Shingare, M. S.; Beilstein, J.
Org. Chem. 2011, 7, 53; (c) Manabe, K.; Mori, Y.; Wakabayashi, T.; Nagayama, S.;
Kobayashi, S. J. Am. Chem. Soc. 2000, 122, 7202.
14. Wang, L.-M.; Jiao, N.; Qiu, J.; Yu, J.-J.; Liu, J.-Q.; Guo, F.-L.; Liu, Y Tetrahedron
2010, 1, 339.
(1.0 mmol), o-phenylenediamine 5 (1.0 mmol), TBAB (0.0483 g, 15 mol %) and
distilled water (5.0 mL) was taken in a round bottom flask. The reaction was
performed in the same way as described above.
Spectral data of representative compounds:
6H-indolo[2,3-b]quinoxaline 7a (Table 3, entry 1): Yellow solid; mp 290–292 °C;
IR (KBr, cmꢀ1): 3095–3200, 1620, 1455, 756; 1H NMR (300 MHz, DMSO-d6): d
7.35 (t, 1H, J = 7.8 Hz, Ar-H), 7.52–7.79 (m, 1H, Ar-H), 8.10 (dd, 2H, J = 7.8,
1.2 Hz, Ar-H), 8.32 (dd, 2H, J = 6.6, 1.5 Hz, Ar-H), 8.44 (d, 2H, J = 7.8 Hz, Ar-H),
11.61 (s, 1H, NH, D2O exchangeable); 13C NMR (75 MHz, DMSO-d6): 112.1,
118.9, 120.9, 122.6, 126.1, 127.1, 128.6, 131.1, 131.3, 138.1, 139.7, 140.0, 144.2,
145.7; MS (m/z): 219.2; Anal. Calcd for C14H9N3: C, 76.64; H, 4.10; N, 19.16.
Found; C, 76.51; H, 4.17; N, 19.07.
6-Methyl-6H-indolo[2,3-b]quinoxaline 7b (Table 3, entry 2): Yellow solid; mp
148-150 °C; IR (KBr, cmꢀ1): 1620, 1460, 758; 1H NMR (300 MHz, DMSO-d6): d
2.94 (s, 3H, N-CH3), 6.69 (d, 1H, J = 7.8 Hz, Ar-H), 6.75 (d, 1H, J = 7.8 Hz, Ar-H),
7.25–7.41 (m, 3H, Ar-H), 7.45 (d, 1H, J = 7.2, Hz, Ar-H), 7.74 (d, 1H, J = 7.2 Hz,
Ar-H), 8.38 (dd, 1H, J = 7.8, 1.2 Hz, Ar-H); 13C NMR (75 MHz, DMSO-d6): 30.0,
110.7, 114.8, 115.2, 117.4, 118.6, 121.2, 123.4, 127.9, 129.4, 131.5, 131.6, 131.8,
149.4, 155.7; MS (m/z): 233.2; Anal. Calcd for C15H11N3: C, 77.18; H, 4.71; N,
18.01. Found; C, 77.26; H, 4.63; N, 18.13.
15. Typical experimental procedure for synthesis of 4a: To a mixture of indole-2,3-
dione 1a (1.0 mmol) and o-aminothiophenol 2 (1.0 mmol) in distilled water
(5.0 mL), was added TBAB (0.0483 g, 15 mol %). This reaction mixture was
18. Reissert, A.; Hoppmann, H. Ber. 1924, 57B, 972.
19. Hassaan, A. M.; Kalifa, M. A.; Shehata, A. Z. Bull. Soc. Chim. Belg. 1995, 104, 121.