Synthesis of 6H-isoindolo[2,1-a]indol-6-ones through wittig reaction and tandem reductive cyclization-lactamization

Article abstract of DOI:10.1002/ejoc.201300047

A convenient and efficient two-step route to 6H-Isoindolo[2,1-a]indol-6- ones has been developed starting from o-nitrobenzaldehydes. The methodology involves Wittig reaction followed by tandem reductive cyclization-lactamization. A series of isoindoloindo

Full text of DOI:10.1002/ejoc.201300047

FULL PAPER
DOI: 10.1002/ejoc.201300047
Synthesis of 6H-Isoindolo[2,1-a]indol-6-ones Through Wittig Reaction and
Tandem Reductive Cyclization–Lactamization
Hari K. Kadam[a] and Santosh G. Tilve*[a]
Keywords: Synthetic methods / Nitrogen heterocycles / Wittig reactions / Domino reactions / Reduction / Lactams
A convenient and efficient two-step route to 6H-Isoind-
olo[2,1-a]indol-6-ones has been developed starting from o-
nitrobenzaldehydes. The methodology involves Wittig reac-
tion followed by tandem reductive cyclization–lactamization.
A series of isoindoloindolones incorporating different sub-
stituents on the indole nucleus has been prepared.
Introduction
Nitrogen-containing fused heterocyclic compounds are
widely studied in chemistry and biology because of their
varied biological properties and frequent natural occur-
rence. 6H-Isoindolo[2,1-a]indol-6-one (1) belongs to one
such class. Although, to the best of our knowledge, this
structural motif has yet to be revealed in any naturally oc-
curring compound or metabolites, these compounds (Fig-
ure 1) are still widely studied because of their promising
biological activities including anticancer, antitumor, anti-
bacterial, and antifungal activity. For example, 2-hydroxy-
8,9-dimethoxy-6H-isoindolo[2,1-a]indol-6-one (2a) has sub-
nanomolar affinity for the melatonin binding site MT3,
which is a quinone reductase-2 enzyme.[1] 10-Chloro-7-[2-
(diethylamino)ethylamino]-6H-isoindolo[2,1-a]indol-6-one
(2b), 3-(diethylamino)-N-(6-oxo-6H-isoindolo[2,1-a]indol-
2-yl)propanamide (2c), and 2-amino-6H-isoindolo[2,1-a]-
indol-6-one (2d) all show DNA binding abilities and anti-
proliferative effects against HT-29 and L1210 cell lines.[2]
They also display nonspecific topoisomerase II inhibition.
6H-Isoindolo[2,1-a]indol-6-one (1) is also used as a precur-
sor for the synthesis of NorA efflux pump inhibitors.[3]
A diverse range of approaches for the synthesis of iso-
indoloindolones have been reported. Pd(OAc)2 promoted
oxidative intramolecular cyclization, reported by Itahara,[4]
was extensively used as a simple procedure giving reason-
able yields. Monneret et al.[2,5] synthesized isoindoloindol-
ones using intramolecular Wittig cyclization as a key step.
Estevez’s group[6] developed a copper-mediated intramolec-
ular cyclization approach using 2-(2-aminophenylethynyl)-
benzoic acid esters for the synthesis of isoindoloindolones.
Boussard[1] and co-workers accomplished the synthesis of
Figure 1. 6H-Isoindolo[2,1-a]indol-6-one (1) and similar biolo-
gically important compounds.
2a from methyl 2-[2-(5-hydroxy-2-nitrophenyl)acetyl]benz-
oate through Raney-nickel-mediated reduction followed by
base treatment. McNab’s group[7] developed a cascade ap-
proach involving sigmatropic shift–elimination–cyclization
reaction of methyl 2-(indol-1-yl)benzoate by flash vacuum
pyrolysis (FVP). Muthusubramanian et al.[8] prepared 6H-
isoindolo[2,1-a]indol-6-one (1) by copper-catalyzed domino
sp-sp2 decarboxylative cross-coupling–cycloisomerization–
cyclization reaction. Bao[9] and co-workers prepared a series
of isoindoloindolones from ortho-gem-dibromovinyl aniline
through one-pot sequential Cu catalyzed C–N coupling and
Pd catalyzed C–H activation reaction. Griffiths et al.[10] de-
veloped a route to isoindoloindolones starting from 2-(N-
phthaloyl)benzoic acids via β-ketophosphonates. However,
many of these syntheses are either lengthy or involve com-
plex precursors, thus, a simple, efficient, and versatile syn-
[a] Department of Chemistry, Goa University,
Taleigao Plateau, Goa 403206, India
Fax: +91-832-2452886
E-mail: stilve@unigoa.ac.in
Homepage: http://www.unigoa.ac.in
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201300047.
4280
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Synthesis of 6H-Isoindolo[2,1-a]indol-6-ones
thetic route would increase the scope for preparing structur-
ally similar derivatives for biological and other studies.
Conducting the reaction with triethylphosphite[13] re-
quired the shortest reaction time and yielded the final prod-
For several years, our group has been exploring tandem uct 1a directly in 56% yield. Less encouraging results were
or one-pot syntheses.[11] In this context, we herein report obtained when the Mo catalyst[14] was used for the re-
a two-step synthesis of 6H-isoindolo[2,1-a]indol-6-one (1) ductive cyclization. Good yields were achieved only with
using a Wittig reaction and tandem reductive cyclization– PPh3 at high temperature,[15] giving the desired product 1a
lactamization sequence (Scheme 1). A series of structurally in 75% yield. During this one-pot experiment, tandem re-
similar isoindoloindolones is prepared from appropriate o-
nitrobenzaldehydes as starting material.
Results and Discussion
Our approach to 1 is projected in the retrosynthetic
analysis shown in Scheme 1. We envisioned achieving iso-
indoloindolone 1 by lactamization from ethyl 2-(1H-indol-
2-yl)benzoate (3), which, in turn, could be obtained from
ethyl 2-(2-nitrostyryl)benzoate (4) through reductive cycli-
zation. The latter compound could be obtained by Wittig
reaction of phosphorane 5 and 2-nitrobenzaldehyde (6).
Scheme 3. Synthetic scheme depicting the two-step synthesis of 6H-
isoindolo[2,1-a]indol-6-ones 1.
Table 2. Synthesis of 6H-isoindolo[2,1-a]indol-6-ones (Scheme 3).
Scheme 1. Retrosynthetic scheme.
Following this strategy, we started our synthesis with the
preparation of Wittig salt 7 from ethyl o-toluate by benzylic
bromination[12] followed by addition of PPh3 (Scheme 2).
Phosphonium salt 7 was then mixed with aldehyde 6 fol-
lowed by addition of base to obtain the required Wittig
product 4 directly in 86% yield.
Scheme 2. Preparation of Wittig salt 7.
For the projected reductive cyclization step, a number of
different reagent systems were tried; the results are summa-
rized in Table 1.
Table 1. Tandem reductive cyclization–lactamization reaction.
Entry
Reaction conditions
Yield (%)[a]
1
2
P(OEt)3, reflux, 30 min
[MoO2Cl2dmf2] (10 mol-%),
PPh3, toluene, reflux, 12 h
PPh3, Ph2O, reflux, 4 h
56
51
3
75
[a] Isolated yield after column chromatography. [b] Reproducible
yield at 10 mmol (2 g) scale.
[a] Isolated yield after column chromatography.
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H. K. Kadam, S. G. Tilve
FULL PAPER
2.8 mmol) were dissolved in chloroform/methanol (8:2, 20 mL) and
stirred at room temperature. Triethylamine (0.202 g, 3.2 mmol) was
added slowly with stirring and the mixture was stirred at room
temperature for 12 h. On completion of the reaction (monitored
with TLC), solvent was removed under reduced pressure and water
(20 mL) was added. The mixture was extracted in EtOAc (3ϫ
15 mL) and the combined organic layers were washed with brine
(10 mL), dried with anhyd. Na2SO4, concentrated under reduced
pressure, and purified by flash chromatography (EtOAc/hexanes,
20%).
ductive cyclization–lactamization reaction took place. This
protocol was further extended to the preparation of a series
of substituted isoindoloindolones (Scheme 3).
Introduction of a halogen group on the heterocycle is
known to enhance the bioactivity profile. We therefore used
5-chloro-2-nitrobenzaldehyde (6b) for the preparation of 2-
chloro-6H-isoindolo[2,1-a]indol-6-one
(1b).
Similarly,
methoxy-, dimethoxy-, methylenedioxy- and trimethoxy-
substituted isoindoloindolones 1c–f were also synthesized
(Table 2). The efficiency of the methodology was tested on
larger scale and yields were found to be reproducible even
at 10 mmol (2 g) scale.
Ethyl 2-(2-Nitrostyryl)benzoate (4a): Pale-yellow solid; m.p. 87–
88 °C.[17] IR (KBr): ν = 1344, 1522, 1712, 2990, 3080 cm–1. 1H
˜
NMR (400 MHz, CDCl3): δ = 1.35 (t, J = 7.2 Hz, 3 H), 4.34 (q, J
= 7.2 Hz, 2 H), 6.85–6.95 (m, 3 H), 7.11–7.20 (m, 5 H), 7.90 (d, J
= 8.0 Hz, 1 H), 7.95 (d, J = 8.0 Hz, 1 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 14.34 (CH3), 61.16 (CH2), 124.49 (CH),
126.16 (CH), 127.39 (CH), 127.81 (CH), 129.69 (Cq), 130.52 (CH),
131.40 (CH), 131.87 (CH), 132.79 (CH), 132.85 (CH), 132.91 (CH),
133.31 (Cq), 138.34 (Cq), 148.34 (Cq), 166.94 (Cq) ppm.
A probable mechanism[16] for product formation in the
tandem reductive cyclization–lactamization reaction is de-
picted in Scheme 4.
Ethyl 2-(5-Chloro-2-nitrostyryl)benzoate (4b): Pale-yellow solid;
m.p. 68–69 °C. IR (KBr): ν = 1344, 1520, 1711, 2982, 3063 cm–1.
˜
1H NMR (400 MHz, CDCl3): δ = 1.36 (t, J = 7.2 Hz, 3 H), 4.33
(q, J = 7.2 Hz, 2 H), 6.82–6.91 (m, 3 H), 7.17–7.26 (m, 4 H), 7.90–
7.95 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 14.31 (CH3),
61.23 (CH2), 124.92 (CH), 126.01 (CH), 127.79 (CH), 127.92 (CH),
129.68 (Cq), 130.72 (CH), 131.11 (CH), 132.03 (CH), 132.47 (CH),
133.91 (CH), 135.13 (Cq), 137.67 (Cq), 139.08 (Cq), 146.57 (Cq),
166.77 (Cq) ppm. HRMS: m/z calcd. for C17H14ClNO4Na [M +
Na]+ 354.0509; found 354.0509. C17H14ClNO4 (331.75): calcd. C
61.55, H 4.25, N 4.22; found C 61.73, H 4.17, N 4.36.
Ethyl 2-(5-Methoxy-2-nitrostyryl)benzoate (4c): Yellow oil. IR
Scheme 4. Proposed mechanism.
(neat): ν = 1335, 1525, 1711, 2982, 3062 cm–1. 1H NMR (400 MHz,
˜
CDCl3): δ = 1.28 (t, J = 7.2 Hz, 3 H), 3.36 (s, 3 H), 4.28 (q, J =
7.2 Hz, 2 H), 6.33 (s, 1 H), 6.62 (d, J = 9.2 Hz, 1 H), 6.83 (d, J =
8.4 Hz, 1 H), 6.90 (d, J = 12.0 Hz, 1 H), 7.09–7.15 (m, 3 H), 7.83
(d, J = 7.6 Hz, 1 H), 7.94 (d, J = 9.2 Hz, 1 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 14.28 (CH3), 55.52 (CH3), 61.12 (CH2),
113.80 (CH), 116.69 (CH), 127.10 (CH), 127.28 (CH), 127.33 (Cq),
129.74 (Cq), 130.31 (CH), 131.24 (CH), 131.89 (CH), 132.24 (CH),
136.08 (CH), 138.27 (Cq), 141.20 (Cq), 162.66 (Cq), 166.91
(Cq) ppm. HRMS: m/z calcd. for C18H17NO5Na [M + Na]+
Conclusions
We have developed a simple and efficient two-step
method for the synthesis of 6H-isoindolo[2,1-a]indol-6-one
derivatives 1 through Wittig reaction and tandem reductive
cyclization–lactamization. The versatility of this method
has been demonstrated by the synthesis of a series of struc- 350.1004; found 350.1004.
turally related isoindoloindolones.
Ethyl 2-[2-(6-Nitrobenzo[d][1,3]dioxol-5-yl)vinyl]benzoate (4d): Yel-
low solid; m.p. 123–124 °C. IR (KBr): ν = 1321, 1518, 1712, 2982,
˜
1
3125 cm–1. H NMR (400 MHz, CDCl3): δ = 1.35 (t, J = 7.2 Hz,
3 H), 4.32 (q, J = 7.2 Hz, 2 H), 5.92 (s, 2 H), 6.31 (s, 1 H), 6.84–
6.91 (m, 2 H), 7.10 (d, J = 12.4 Hz, 1 H), 7.10–7.16 (m, 2 H), 7.51
(s, 1 H), 7.91 (d, J = 8.0 Hz, 1 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 14.31 (CH3), 61.16 (CH2), 102.80 (CH2), 105.16 (CH),
111.19 (CH), 126.98 (CH), 127.42 (CH), 129.62 (Cq), 130.53 (CH),
130.68 (Cq), 131.35 (CH), 131.78 (CH), 131.99 (CH), 138.29 (Cq),
142.26 (Cq), 147.05 (Cq), 151.47 (Cq), 166.97 (Cq) ppm. HRMS:
m/z calcd. for C18H15NO6Na [M + Na]+ 364.0797; found 364.0806.
Experimental Section
General: Commercial reagents were purchased from Sigma–Aldrich
and used without further purification. Solvents were distilled prior
to use. Reactions were monitored by thin-layer chromatography
(TLC Silica gel 60 F254 purchased from Merck). Column
chromatography was performed on silica gel (60–120 mesh). 1H
NMR (400 MHz) and 13C NMR (100 MHz) were recorded with a
Bruker 400 instrument using CDCl3 or DMSO as solvent and TMS
as internal standard. HRMS were recorded with a MicroMass ES-
QTOF. IR spectra were recorded with a Shimatzu FTIR instru-
ment. Melting points are recorded with a Thiele apparatus and are
uncorrected. Elemental analyses were performed with an Ele-
mentar CHNS instrument.
Ethyl 2-(4,5-Dimethoxy-2-nitrostyryl)benzoate (4e): Yellow solid;
m.p. 56–57 °C. IR (KBr): ν = 1345, 1530, 1709, 2990, 3075 cm–1.
˜
1H NMR (400 MHz, CDCl3): δ = 1.34 (t, J = 7.2 Hz, 3 H), 3.32
(s, 3 H), 3.84 (s, 3 H), 4.33 (q, J = 7.2 Hz, 2 H), 6.31 (s, 1 H), 6.89
(d, J = 8.4 Hz, 1 H), 7.01 (d, J = 12.0 Hz, 1 H), 7.14–7.19 (m, 3
H), 7.57 (s, 1 H), 7.88 (d, J = 7.6 Hz, 1 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 13.29 (CH3), 54.87 (CH3), 55.21 (CH3),
60.16 (CH2), 106.30 (CH), 113.18 (CH), 126.25 (CH), 126.36 (CH),
127.11 (Cq), 128.80 (Cq), 129.17 (CH), 130.43 (CH), 130.79 (CH),
General Procedure for the Synthesis of Ethyl 2-(2-Nitrostyryl)benz-
oates 4a–f: o-Nitrobenzaldehyde 6a–f (2 mmol) and [2-(ethoxycar-
bonyl)benzyl]triphenylphosphonium
bromide
(7;
1.012 g,
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Synthesis of 6H-Isoindolo[2,1-a]indol-6-ones
130.93 (CH), 137.71 (Cq), 139.46 (Cq), 146.72 (Cq), 151.40 (Cq), 145.11 (Cq), 147.42 (Cq), 162.66 (Cq) ppm. HRMS: m/z calcd. for
166.08 (Cq) ppm. HRMS: m/z calcd. for C19H19NO6Na [M +
C16H9NO3Na [M + Na]+ 286.0480; found 286.0480.
Na]+ 380.1110; found 380.1111.
2,3-Dimethoxy-6H-isoindolo[2,1-a]indol-6-one (1e): Light-brown so-
Ethyl 2-(4,5,6-Trimethoxy-2-nitrostyryl)benzoate (4f): Yellow solid;
lid; m.p. 168–169 °C (ref.[9] 160–161 °C). IR (KBr): ν = 1445, 1724,
˜
m.p. 45–46 °C. IR (KBr): ν = 1344, 1527, 1710, 2950, 3060 cm–1. 3055 cm–1. 1H NMR (400 MHz, CDCl3): δ = 3.83 (s, 3 H), 3.89 (s,
˜
1H NMR (400 MHz, CDCl3): δ = 1.31 (t, J = 7.2 Hz, 3 H), 3.82 3 H), 6.39 (s, 1 H), 6.82 (s, 1 H), 7.19–7.20 (m, 1 H), 7.32–7.38 (m,
(s, 3 H), 3.86 (s, 3 H), 3.90 (s, 3 H), 4.30 (q, J = 7.2 Hz, 2 H), 6.93
3 H), 7.61 (d, J = 7.2 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3):
(d, J = 16.0 Hz, 1 H), 7.20 (s, 1 H), 7.28 (t, J = 8.0 Hz, 1 H), 7.45 δ = 55.23 (CH3), 55.33 (CH3), 96.01 (CH), 102.71 (CH), 103.29
(t, J = 8.0 Hz, 1 H), 7.66 (d, J = 8.0 Hz, 1 H), 7.84 (s, 1 H), 7.86 (CH), 119.49 (CH), 124.19 (CH), 125.75 (Cq), 127.02 (CH), 127.20
(d, J = 8.0 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 14.31 (Cq), 132.47 (Cq), 132.66 (CH), 134.10 (Cq), 136.56 (Cq), 145.83
(CH3), 56.36 (CH3), 61.05 (CH2), 61.16 (CH3), 61.22 (CH3), 104.08 (Cq), 148.36 (Cq), 161.73 (Cq) ppm. HRMS: m/z calcd. for
(CH), 121.21 (Cq), 121.50 (CH), 127.38 (CH), 127.60 (CH), 129.24 C17H13NO3Na [M + Na]+ 302.0793; found 302.0792.
(Cq), 130.43 (CH), 132.15 (CH), 133.81 (CH), 139.11 (Cq), 144.51
(Cq), 146.85 (Cq), 151.99 (Cq), 152.46 (Cq), 167.23 (Cq) ppm.
1,2,3-Trimethoxy-6H-isoindolo[2,1-a]indol-6-one (1f): Brown solid;
1
m.p. 156–158 °C. IR (KBr): ν = 1437, 1724, 3061 cm–1. H NMR
˜
HRMS: m/z calcd. for C20H21NO7Na [M + Na]+ 410.1216; found
(400 MHz, CDCl3): δ = 3.78 (s, 3 H), 3.85 (s, 3 H), 3.98 (s, 3 H),
410.1215.
6.55 (s, 1 H), 7.09 (s, 1 H), 7.17–7.19 (m, 1 H), 7.33–7.37 (m, 2 H),
7.61 (d, J = 8.0 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
56.48 (CH3), 61.13 (CH3), 61.34 (CH3), 92.76 (CH), 101.45 (CH),
120.53 (Cq), 120.60 (CH), 125.25 (CH), 128.10 (CH), 130.46 (Cq),
133.40 (Cq), 133.71 (CH), 134.83 (Cq), 136.58 (Cq), 138.26 (Cq),
147.20 (Cq), 154.09 (Cq), 162.75 (Cq) ppm. HRMS: m/z calcd. for
C18H15NO4Na [M + Na]+ 332.0899; found 332.0895.
General Procedure for the Synthesis of 6H-Isoindolo[2,1-a]indol-6-
ones 1a–f: A mixture of ethyl 2-(2-nitrostyryl)benzoate 4a–f
(1 mmol) and triphenylphosphane (576 mg, 2.2 mmol) was heated
to reflux in diphenyl ether (10 mL) for 4 h. After cooling, the mix-
ture was purified by chromatography (silica gel; hexanes then
EtOAc/hexanes 10%) to afford the isoindolo-indolones 1a–f.
6H-Isoindolo[2,1-a]indol-6-one (1a): Yellow solid; m.p. 153–154 °C
Supporting Information (see footnote on the first page of this arti-
cle): Spectral data of all the products are given.
(ref.[7] 153–154 °C). IR (KBr): ν = 1444, 1725, 3057 cm–1. 1H NMR
˜
(400 MHz, CDCl3): δ = 6.54 (s, 1 H), 7.08 (t, J = 8.0 Hz, 1 H),
7.21 (t, J = 8.0 Hz, 1 H), 7.27 (m, 1 H), 7.36 (d, J = 8.0 Hz, 1 H),
7.44 (m, 2 H), 7.67 (d, J = 7.6 Hz, 1 H), 7.80 (d, J = 8.0 Hz, 1
H) ppm. 13C NMR (CDCl3): δ = 103.54 (CH), 113.34 (CH), 121.26
(CH), 122.30 (CH), 123.90 (CH), 125.29 (CH), 126.33 (CH), 128.81
(CH), 133.59 (Cq), 133.72 (CH), 133.86 (Cq), 134.52 (Cq), 134.66
(Cq), 138.83 (Cq), 162.67 (Cq) ppm. C15H9NO (219.24): calcd. C
82.18, H 4.14, N 6.39; found C 82.39, H 4.34, N 6.73.
Acknowledgments
The authors are thankful to the Department of Science and Tech-
nology (DST), New Delhi and the Council for Scientific and Indus-
trial Research (CSIR), New Delhi for financial support, and IISc
(Bangalore) for use of the HRMS facility. H. K. K. acknowledges
CSIR (New Delhi) for the award of a NET Senior Research Fellow-
ship.
2-Chloro-6H-isoindolo[2,1-a]indol-6-one (1b): Yellow solid; m.p.
160–162 °C. IR (KBr): ν = 1440, 1728, 3059 cm–1. 1H NMR
˜
(400 MHz, CDCl3): δ = 6.48 (s, 1 H), 7.15 (d, J = 7.6 Hz, 1 H),
7.28–7.31 (m, 1 H), 7.34 (s, 1 H), 7.45–7.46 (m, 2 H), 7.68–7.73 (m,
2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 102.56 (CH), 114.05
(CH), 121.50 (CH), 121.96 (CH), 125.47 (CH), 126.31 (CH), 129.24
(CH), 129.36 (Cq), 131.87 (Cq), 133.64 (Cq), 133.96 (CH), 134.36
(Cq), 135.70 (Cq), 140.08 (Cq), 162.44 (Cq) ppm. HRMS: m/z
calcd. for C15H8ClNOH [M + H]+ 254.0373; found 254.0370.
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2-Methoxy-6H-isoindolo[2,1-a]indol-6-one (1c): Yellow solid; m.p.
160–161 °C (ref.[5] 165–166 °C). IR (KBr):
ν = 1440, 1724,
˜
3057 cm–1. 1H NMR (400 MHz, CDCl3): δ = 3.72 (s, 3 H), 6.37 (s,
1 H), 6.75 (d, J = 8.0 Hz, 1 H), 6.79 (s, 1 H), 7.20 (d, J = 8.0 Hz,
1 H), 7.32–7.37 (m, 2 H), 7.58–7.63 (m, 2 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 55.69 (CH3), 103.40 (CH), 105.86 (CH),
113.77 (CH), 113.94 (CH), 121.07 (CH), 125.09 (CH), 128.21 (Cq),
128.71 (CH), 133.50 (CH), 133.9 (Cq), 134.59 (Cq), 135.49 (Cq),
139.66 (Cq), 156.69 (Cq), 162.30 (Cq) ppm. HRMS: m/z calcd. for
C16H11NO2Na [M + Na]+ 272.0687; found 272.0687. C16H11NO2
(249.27): calcd. C 77.10, H 4.45, N 5.62; found C 77.40, H 4.40, N
5.99.
6H-(1,3)Dioxo(4,5-f)isoindolo[2,1-a]indol-6-one (1d): Orange solid;
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1
m.p. 201–202 °C. IR (KBr): ν = 1468, 1724, 3057 cm–1. H NMR
˜
(400 MHz, CDCl3): δ = 5.91 (s, 2 H), 6.38 (s, 1 H), 6.75 (s, 1 H),
7.20 (t, J = 7.4 Hz, 1 H), 7.31 (s, 1 H), 7.34 (d, J = 7.6 Hz, 1 H),
7.38 (t, J = 7.6 Hz, 1 H), 7.63 (d, J = 7.6 Hz, 1 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 95.36 (CH), 101.36 (CH2), 101.54 (CH),
103.88 (CH), 120.51 (CH), 125.28 (CH), 128.10 (CH), 128.23 (Cq),
128.80 (Cq), 133.35 (Cq), 133.77 (CH), 135.14 (Cq), 137.79 (Cq),
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H. K. Kadam, S. G. Tilve
FULL PAPER
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Received: January 11, 2013
Published Online: May 23, 2013
4284
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 4280–4284