Montmorillonite-KSF-catalyzed synthesis of 4-heteroarylidene-N-arylhomophthalimides by Knoevenagel condensation

Article abstract of DOI:10.1007/s11164-014-1677-7

A simple, efficient and rapid method for clay-catalyzed Knoevenagel condensation of heterocyclic aldehydes with active methylene compound under reflux condition is reported. This protocol offers high yield, shorter time and simple work procedure. The protocol does not require column chromatography for purification, and the process is environmentally benign.

Full text of DOI:10.1007/s11164-014-1677-7

Res Chem Intermed
DOI 10.1007/s11164-014-1677-7
Montmorillonite-KSF-catalyzed synthesis
of 4-heteroarylidene-N-arylhomophthalimides
by Knoevenagel condensation
•
Varadhan Krishnakumar Fazlur-Rahman Nawaz Khan
•
•
Badal Kumar Mandal Euh-Duck Jeong Jong Sung Jin
•
Received: 15 November 2013 / Accepted: 16 April 2014
Ó Springer Science+Business Media Dordrecht 2014
Abstract A simple, efficient and rapid method for clay-catalyzed Knoevenagel
condensation of heterocyclic aldehydes with active methylene compound under
reflux condition is reported. This protocol offers high yield, shorter time and simple
work procedure. The protocol does not require column chromatography for purifi-
cation, and the process is environmentally benign.
Keywords Montmorillonite KSF ꢀ 4-Heteroarylidene-N-arylhomophthalimides ꢀ
Knoevenagel condensation
Introduction
In recent decades, organic reactions have been performed using the concept of green
chemistry [1, 2]. Use of heterogeneous catalysts offers researchers an important
Electronic supplementary material The online version of this article (doi:10.1007/s11164-014-1677-7)
contains supplementary material, which is available to authorized users.
V. Krishnakumar ꢀ F.-R. N. Khan (&)
Organic and Medicinal Chemistry Research Laboratory, Organic Chemistry Division, School of
Advanced Sciences, VIT-University, Vellore 632 014, Tamil Nadu, India
e-mail: nawaz_f@yahoo.co.in
V. Krishnakumar ꢀ B. K. Mandal (&)
Trace Elements Speciation Research Laboratory, Environmental and Analytical Chemistry Division,
School of Advanced Sciences, VIT-University, Vellore 632 014, Tamil Nadu, India
e-mail: mbadal@hotmail.com
F.-R. N. Khan ꢀ E.-D. Jeong (&) ꢀ J. S. Jin (&)
Korea Basic Science Institute, Busan Center, Busan 618 230, South Korea
e-mail: edjeong@kbsi.re.kr
J. S. Jin
e-mail: jsjin@kbsi.re.kr
123

V. Krishnakumar et al.
vehicle to achieve target molecules in a greener way [3–6]. Although these reactions
can be carried out with traditional catalysts such as Lewis and Brønsted acids, bases
and metal salts, such reagents are corrosive and dangerous to the environment, as
well as not being recoverable from the reaction mixture. Montmorillonite clay
catalysis has provided promising solutions for a wide range of organic transfor-
mations [7–9], with such processes proceeding with high selectivity, straightforward
reactions, shorter reaction time, and high product yield and purity. These catalysts
are also inexpensive, readily available and easily recovered and recycled.
Quinolines and isoquinolinones are common moieties in biologically active
compounds, having significant pharmaceutical [10], synthetic and material appli-
cations [11], including medicinal properties such as anti-microbial [12], anti-
inflammatory [13], anti-oxidant [14] and anti-cancer activities [15, 16]; they are also
used as dyes and pigments [17], and in sensors and organic light-emitting diodes
(OLEDs) [18, 19] and positron emission tomography (PET) scan imaging probes
[20]. Isoquinolinone, a structural unit of several naturally occurring alkaloids [21,
22], has attracted the attention of both synthetic and natural product chemists due to
diverse biological activities [23, 24]. Isoquinolinones form key intermediates in
synthesis of various alkaloids such as indenoisoquinolines [25] and protoberberines
[26]. Quinolines are functionalized intermediates in preparation of many pharma-
ceutically active compounds [27, 28], such as camptothecin [29, 30] and luotonins
[31]. Introduction of an additional heterocyclic moiety into the molecule may
significantly increase the biological action of these compounds [32]. C–C bond-
forming reactions are of great interest in many organic transformations [33–50]
involved in total synthesis and synthesis of many natural products and function-
alized intermediates [35–37]. Herein, we report a facile synthesis of 4-[(2-
chloroquinolin-3-yl)methylene]-N-arylhomophthalimide from N-arylhomophthali-
mide in excellent yield. The 2-chloro-3-formylquinolines (1) and corresponding N-
arylhomophthalimides (2) required for our study were obtained from our earlier
reports [38, 39].
Results and discussion
In the preliminary investigation, the 2-chloro-3-formylquinoline 1a was treated with
N-arylhomophthalimide 2a in the presence of piperidine as base with ethanol
(EtOH) as solvent under reflux condition to give the Knoevenagel product 3a in
55 % yield (Scheme 1).
We further examined different bases and solvents to optimize the reaction
conditions for condensation. The observed results are listed in Table 1. In the
comparison of other bases, triethylamine (TEA) gave good yield of product
(Table 1, entry 6). Generally, the reaction was incomplete in the presence of
inorganic bases such as K2CO3 and t-BuOK. Piperidine and the strong base NaH
gave moderate yield of the desired product. The reaction required more time in the
absence of catalyst with lower product yield (Table 1, entry 1), and the reaction was
generally incomplete even after 12 h.
123

Synthesis of 4-heteroarylidene-N-arylhomophthalimides
O
N
O
CHO
O
N
Base
N
EtOH, reflux
N
Cl
O
Cl
1a
2a
3a
Scheme 1 Synthesis of 4-[(2-chloroquinolin-3-yl)methylene]-N-arylhomophthalimide (3a)
Table 1 Optimization of the catalyst
S. no.
Catalyst
Time (h)
Yield (%)a
1
2
None
12
4
35
45
56
60
55
80
68
75
92
80
K2CO3
3
t-BuOK
NaH
4
4
1
5
Piperidine
TEA
4
6
2
7
Basic alumina
KF/alumina
Mont. KSF
Zeolite
4
8
3
9
1
10
1
Reaction carried out with 1 equiv. of 1a and 2b. Catalyst loading (entries 2–6, 1 eq.; entries 6–9, 100 mg)
in 10 mL EtOH under reflux condition
a
Isolated yield
Table 2 Effect of solvent
Entry
1
2
3
4
5
Solvent
MeOH
55
EtOH
92
CHCl3
58
CH2Cl2
52
CH3CN
62
Yield (%)
Reaction carried out with 1 mmol 1a with 2b, 100 mg of mont. KSF catalyst, under reflux condition
Based on this evidence, we extended the scope of the work to use a reusable
heterogeneous catalyst for our reaction. Initially, we tried basic alumina as a
catalyst, which gave a moderate yield of 68 %. Furthermore, we investigated
various heterogeneous catalysts, and montmorillonite KSF offered the best yield and
high purity of the product (92 %) (Table 1, entry 8). In addition, we optimized the
effect of solvent on the reaction. EtOH used as solvent for the reaction gave the
maximum product yield (Table 2, entry 2). MeOH, CHCl3, CH2Cl2 and CH3CN
gave moderate yield (Table 2, entries 1, 3–5).
123

V. Krishnakumar et al.
It is noteworthy that mont. KSF was found to be more efficient and took less time to
complete the reaction. Based on the above facts, we selected mont. KSF as an efficient
base for our reaction (Table 3). The products 3a–n were isolated from the reaction
mass by simple filtration with minimum amount of EtOH washing without need for
column chromatography. The additional advantage of this method is the shorter
reaction time (50–120 min). The reaction proceeds well in the presence of inexpensive
clay with high yield and without the need for special equipment such as microwave
[51], ultrasonication [52], microreactor [53] or ball-mill method [54–56].
In the 1H nuclear magnetic resonance (NMR) spectra, the peak at d 4.24 appeared
as a singlet of two protons at C4-position of 2a, and d 10.57 appeared as a singlet of
one proton due to the aldehyde group of compound 1a. Both disappeared and a new
peak appeared at d 8.21 as singlet of alkenic proton for product 3a. There is no
coupling partner for the alkenic proton present in the product 3a, because the
neighbouring carbon does not have a proton, and it appeared as a singlet. The trans
orientation of the proton resulted in the maximum value at 8.21 ppm in the 1H NMR
spectrum. Generally, alkenic protons appear in the 6–7 ppm region. Due to the
bulkier nature of the 2-chloro-3-formylquinoline, the d value of the alkenic proton
shifted downfield to 8.21 ppm and was obtained as E-isomer, as further supported
by the literature report [56]. Condensation of Knoevenagel product was also
supported by the 13C NMR spectra, in which the d 36.98 of C4-carbon peak
disappeared and a new peak appeared for alkenic carbon at d 139.05. The liquid
chromatography–mass spectroscopy (LC–MS) spectra of synthesized compounds 3a
and 3g showed molecular-ion peaks at m/e of 410.00 and 446.60. All these data
were found to be in good agreement with the assigned structure.
Importantly, purification of the product and recovery of the catalyst were very
easy. After completion of the reaction, the reaction mixture was cooled to room
temperature, then the formed precipitate was filtered and washed with small amount
of EtOH. The collected material was dissolved in EtOAc, and the catalyst was
separated by simple filtration. The filtrate was evaporated under reduced pressure,
and the obtained material was pure enough for further analysis. The collected
catalyst was dried in a hot-air oven for 1 h, then used for further cycles.
The reusability of the catalyst was checked, resulting in 92, 89 and 88 % in
subsequent cycles. These recoveries indicate that no significant loss of catalytic
activity was observed.
Experimental
Materials and methods
Melting points were measured with open capillary tubes and were corrected with
benzoic acid as reference. The progress of the reaction was monitored by thin-layer
chromatography (TLC) plates. Infrared (IR) spectra (KBr, t cm-1) were recorded on
a JASCO FT-IR 4100 spectrometer. 1H NMR (400 MHz) and 13C NMR (100 MHz)
spectra were recorded on a Bruker 400-MHz spectrometer in CDCl3 with
tetramethylsilane (TMS) as internal reference. LC–MS analyses were performed
123

Synthesis of 4-heteroarylidene-N-arylhomophthalimides
Table 3 Knoevenagel condensation of N-arylhomophthalimide with 2-chloro-3-formylquinoline
R'
O
R'
O
N
R
Mont. KSF
N
R-CHO
O
EtOH, reflux
O
1a-h
2a-b
3a-n
Compound
R
R0
H
Time (min)
Yield (%)a
92
3a
3b
1a
1b
60
N
N
Cl
Cl
H
70
94
3c
3d
3e
1d
1e
1f
H
H
H
90
45
80
89
94
87
N
Cl
O
N
Cl
N
N
Cl
Cl
3f
1g
H
45
90
3g
3h
1a
1b
Cl
Cl
60
86
85
N
N
Cl
Cl
100
3i
1c
Cl
90
83
N
Cl
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V. Krishnakumar et al.
Table 3 continued
Compound
R
R0
Time (min)
Yield (%)a
79
3j
3k
3l
1d
1e
1f
Cl
35
N
Cl
Cl
Cl
50
91
85
O
N
Cl
120
N
N
Cl
Cl
3m
3n
1g
1h
Cl
H
50
35
90
82
Cl
Reaction carried out with 1 equiv. of 1 and 2, 100 mg mont. KSF, 10 mL EtOH under reflux condition
a
Isolated (recrystallized from hot EtOH)
with an Agilent-1100 series ion trap. Chemicals purchased from Sigma-Aldrich
(India), Sd-Fine (India) were used without further purification.
General procedure for synthesis of 2-chloro-3-formylquinolines 1a–g
To a solution of acetanilide (5 mmol) in dry dimethylformamide (DMF) (20 mmol)
at 0–5 °C with stirring, POCl3 (35 mmol) was added dropwise, and the mixture was
stirred at 80–90 °C for time ranging between 8 and 16 h. The mixture was poured
into crushed ice and stirred for 5 min, and the resulting solid was filtered and
washed well with water and dried. The compounds were subjected to silica gel
column chromatography.
General procedure for synthesis of N-arylhomophthalimides 2a, b
A mixture of homophthalic acid (10 mmol) and anilines (10 mmol) in dry toluene
and 5 mol% nano-ZnO were amended to the suspension. The reaction mixture was
heated under reflux condition. The progress of the reaction was monitored by thin-
layer chromatography. After completion of the reaction, the catalyst was separated
by filtration. The solvent was removed under vacuum, then the crude sample was
purified by silica gel column chromatography using ethyl acetate and n-hexane
mixture as eluant.
123

Synthesis of 4-heteroarylidene-N-arylhomophthalimides
General procedure for synthesis of (E)-4-((2-chloroquinolin-3-yl)methylene)-2-
phenylisoquinoline-1,3(2H,4H)-diones 3a–n
A mixture of 2-chloro-3-formylquinoline 1a–g (1 mmol) was treated with N-
arylhomophthalimide 2a, b (1 mmol) in ethanol, and 100 mg mont. KSF was added
to the suspension. Completion of the reaction was monitored by TLC, after which
the reaction mixture was filtered and recrystallized using hot ethanol. The pure
compound was analyzed by various spectral and analytical methods.
4-((2-Chloroquinolin-3-yl)methylene)-2-phenylisoquinoline-1,3(2H,4H)-dione (3a) Yel-
1
low solid; m.p. 152–154 °C; IR (KBr) 1,710 (C3-CO), 1,674 (C1-CO) cm-1; H
NMR (400 MHz, CDCl3) d 8.31–8.33 (d, J = 7.2 Hz, 2H), 8.22 (s, 1H), 8.08–8.11
(d, J = 8.4 Hz, 1H), 7.80–7.84 (t, J = 7.6 Hz, 1H), 7.72–7.74 (d, J = 8.0 Hz, 1H),
7.53–7.57 (m, 2H), 7.45–7.50 (m, 2H), 7.38–7.40 (d, J = 8.0 Hz, 1H), 7.26–7.31
(m, 4H), ppm; 13C NMR (100 MHz, CDCl3) d 165.10 (C3-CO), 164.04 (C1-CO),
149.17, 147.76, 138.78, 137.96, 135.21, 133.15, 131.66, 131.50, 129.96, 129.69,
129.42, 128.88, 128.61, 128.48, 128.34, 127.85, 127.82, 126.74, 126.65, 126.17,
30.96, ppm; LC–MS m/e calcd. for C25H15ClN2O2 410.08, found 410.00.
4-((2-Chloro-8-methylquinolin-3-yl)methylene)-2-phenylisoquinoline-1,3(2H,4H)-
dione (3b) Yellow solid; m.p. 231–233 °C; IR (KBr) 1,707 (C3-CO), 1,660 (C1-
1
CO) cm-1; H NMR (400 MHz, CDCl3) d 8.48 (s, 1H), 8.33–8.36 (d, J = 6.8 Hz,
1H), 8.08 (s, 1H), 7.98–8.00 (d, J = 8.0 Hz, 1H), 7.77–7.81 (t, J = 6.0 Hz, 1H),
7.60–7.65 (m, 2H), 7.55–7.56 (d, J = 6.8 Hz, 1H), 7.38–7.48 (m, 4H), 7.19–7.21
(m, 2H), 2.74 (s, 3H), ppm; 13C NMR (100 MHz, CDCl3) d 164.10 (C3-CO), 163.57
(C1-CO), 149.50, 147.77, 147.77, 144.32, 139.53, 137.59, 134.70, 134.64, 134.46,
134.46, 134.38, 133.17, 129.86, 129.40, 129.22, 129.06, 128.37, 128.29, 128.16,
127.87, 125.84, 123.32, 21.06, ppm; LC–MS m/e calcd. for C26H17ClN2O2 424.09,
found 425.00.
4-((2-Chloro-6-methylquinolin-3-yl)methylene)-2-phenylisoquinoline-1,3(2H,4H)-
dione (3c) Pale-yellow solid; m.p. 240–242 °C; IR (KBr) 1,715 (C3-CO), 1,673
(C1-CO) cm-1; 1H NMR (400 MHz, CDCl3) d 8.31–8.32 (d, J = 5.2 Hz, 2H), 8.11
(s, 1H), 7.97–7.99 (d, J = 8.4 Hz, 1H), 7.62–7.65 (d, J = 6.8 Hz, 1H), 7.46–7.57
(m, 4H), 7.44 (s, 1H), 7.38–7.40 (d, J = 8.8 Hz, 1H), 7.28–7.31 (m, 3H), 2.74 (s,
3H), ppm; 13C NMR (100 MHz, CDCl3) d 164.93 (C3-CO), 163.87 (C1-CO),
148.11, 146.43, 139.36, 138.04, 137.23, 134.79, 133.99, 133.64, 133.26, 131.54,
129.94, 129.66, 129.61, 128.63, 128.29, 127.96, 126.81, 126.67, 126.60, 125.95,
21.59, ppm; LC–MS m/e calcd. for C26H17ClN2O2 424.09, found 425.00.
4-((2-Chloro-6-methoxyquinolin-3-yl)methylene)-2-phenylisoquinoline-1,3(2H,4H)-
dione (3d) Yellow solid; m.p. 234–236 °C; IR (KBr) 1,714 (C3-CO), 1,672 (C1-
1
CO) cm-1; H NMR (400 MHz, CDCl3) d 8.30–8.33 (d, J = 7.2 Hz, 2H), 8.08 (s,
1H), 7.97–7.99 (d J = 9.2 Hz, 1H), 7.53–7.57 (m, 2H), 7.43–7.50 (m, 3H),
7.37–7.40 (d, J = 7.2 Hz, 1H), 7.28–7.33 (m, 3H), 6.96 (d, J = 2.8 Hz, 1H), 3.90
123

V. Krishnakumar et al.
(s, 3H), ppm; 13C NMR (100 MHz, CDCl3) d 165.08 (C3-CO), 164.03 (C1-CO),
158.69, 146.38, 143.88, 139.14, 136.49, 135.25, 133.13, 131.61, 129.99, 129.90,
129.59, 129.38, 129.09, 128.84, 128.49, 128.23, 127.85, 126.79, 126.17, 124.36,
105.18, 55.71, ppm; LC–MS m/e calcd. for C26H17ClN2O3 440.09, found 441.00.
4-((2-Chloro-7,8-dimethylquinolin-3-yl)methylene)-2-phenylisoquinoline-1,3(2H,4H)-
dione (3e) Pale-orange solid; m.p. 194–196 °C; IR (KBr) 1,708 (C3-CO), 1,668
(C1-CO) cm-1; 1H NMR (400 MHz, CDCl3) d 8.29–8.32 (d, J = 4.8 Hz, 2H), 8.12
(s, 1H), 7.52–7.56 (t, J = 7.2 Hz, 2H), 7.44–7.49 (m, 3H), 7.38–7.42 (t,
J = 7.6 Hz, 1H), 7.25–7.30 (m, 4H), 2.75 (s, 3H), 2.53 (s, 3H), ppm; 13C NMR
(100 MHz, CDCl3) d 165.16 (C3-CO), 164.07 (C1-CO), 147.97, 146.99, 140.01,
139.47, 138.05, 134.30, 133.01, 131.76, 130.56, 129.83, 129.46, 129.35, 128.78,
128.51, 127.82, 127.29, 126.71, 126.15, 125.04, 124.72, 20.87, 13.34, ppm; LC–MS
m/e calcd. for C27H19ClN2O2 438.11, found 439.00.
4-((2-Chlorobenzo[h]quinolin-3-yl)methylene)-2-phenylisoquinoline-1,3(2H,4H)-
dione (3f) Yellow solid; m.p.[300 °C (charring); IR (KBr) 1,710 (C3-CO), 1,657
(C1-CO) cm-1; 1H NMR (400 MHz, CDCl3) d 9.16–9.18 (d, J = 2.4 Hz, 1H), 8.57
(s, 1H), 8.34–8.36 (d, J = 6.4 Hz, 1H), 8.12 (s, 1H), 8.00–8.02 (d, J = 8.0 Hz, 1H),
7.87–7.89 (m, 1H), 7.77–7.86 (m, 2H), 7.69–7.72 (m, 2H), 7.60–7.66 (m, 2H),
7.44–7.48 (m, 2H), 7.36–7.40 (m, 1H), 7.20–7.22 (d, J = 5.2 Hz, 2H), ppm; LC–
MS m/e calcd. for C29H17ClN2O2 460.09, found 461.00.
2-(4-Chlorophenyl)-4-((2-chloroquinolin-3-yl)methylene)-isoquinoline-1,3(2H,4H)-
dione (3g) Yellow solid; m.p. 258–260 °C; IR (KBr) 1,710 (C3-CO), 1,666 (C1-
1
CO) cm-1; H NMR (400 MHz, CDCl3) d 8.30–8.32 (t, J = 3.2 Hz, 2H), 8.21 (s,
1H), 8.09–8.11 (d, J = 8.4 Hz, 1H), 7.82–7.84 (t, J = 5.6 Hz, 1H), 7.72–7.74 (d,
J = 8.0 Hz, 1H), 7.60–7.62 (t, J = 6.0 Hz, 1H), 7.50–7.53 (m, 2H), 7.45–7.47 (m,
1H), 7.38–7.40 (d, J = 7.6 Hz, 1H), 7.30–7.32 (d, J = 4.4 Hz, 1H), 7.23–7.25 (m,
2H), ppm; 13C NMR (100 MHz, CDCl3) d 164.92 (C3-CO), 163.85 (C1-CO),
149.07, 147.79, 139.05, 134.81, 133.61, 133.28, 131.69, 131.46, 129.97, 129.93,
129.74, 129.62, 128.78, 128.14, 127.83, 126.76, 126.60, 125.96, ppm; LC–MS
m/e calcd. for C25H14Cl2N2O2 444.04, found 446.60.
4-((2-Chloro-8-methylquinolin-3-yl)methylene)-2-(4-chlorophenyl)-isoquinoline-
1,3(2H,4H)-dione (3h) Yellow solid; m.p. 240–242 °C; IR (KBr) 1,718 (C3-CO),
1,676 (C1-CO) cm-1; 1H NMR (400 MHz, CDCl3) d 8.29–8.32 (t, J = 6.8 Hz, 2H),
8.15 (s, 1H), 7.64–7.66 (d, J = 6.8 Hz, 1H), 7.38–7.56 (m, 7H), 7.29–7.31 (d,
J = 6.0 Hz, 1H), 7.22–7.25 (m, 2H), 2.81 (s, 3H), ppm; 13C NMR (100 MHz,
CDCl3) d 164.96 (C3-CO), 163.88 (C1-CO), 149.94, 147.03, 139.45, 138.14, 136.96,
134.76, 133.68, 133.25, 131.74, 131.58, 129.95, 129.64, 129.60, 128.39, 127.90,
127.54, 126.77, 126.66, 125.92, 125.70, 17.73, ppm; LC–MS m/e calcd. for
C26H16Cl2N2O2 458.05, found 459.00.
123

Synthesis of 4-heteroarylidene-N-arylhomophthalimides
4-((2-Chloro-6-methylquinolin-3-yl)methylene)-2-(4-chlorophenyl)-isoquinoline-
1,3(2H,4H)-dione (3i) Yellow solid; m.p. 270–272 °C; IR (KBr) 1,710 (C3-CO),
1,668 (C1-CO) cm-1; 1H NMR (400 MHz, CDCl3) d 8.30–8.31 (t, J = 4.0 Hz, 2H),
8.10 (s, 1H), 7.97–7.99 (d, J = 8.4 Hz, 1H), 7.63–7.65 (d, J = 6.8 Hz, 1H),
7.50–7.52 (d, J = 6.8 Hz, 2H), 7.44–7.47 (m, 2H), 7.38–7.40 (d, J = 7.6 Hz, 1H),
7.27–7.30 (m, 1H), 7.23–7.25 (m, 2H), 2.53 (s, 3H), ppm; LC–MS m/e calcd. for
C26H16Cl2N2O2 458.05, found 460.80.
4-((2-Chloro-7-methylquinolin-3-yl)methylene)-2-(4-chlorophenyl)-isoquinoline-
1,3(2H,4H)-dione (3j) Yellowish-orange solid; m.p. [300 °C; IR (KBr) 1,699
(C3-CO), 1,657 (C1-CO) cm-1 1H NMR (400 MHz, CDCl3) d 8.53 (s, 1H),
;
8.32–8.35 (d, J = 6.4 Hz, 1H), 8.08 (s, 1H), 7.97–7.99 (d, J = 8.0 Hz, 1H),
7.77–7.81 (t, J = 8.4 Hz, 2H), 7.70–7.72 (d, J = 8.0 Hz, 1H), 7.60–7.64 (t,
J = 7.6 Hz, 1H), 7.41–7.43 (d, J = 4.8 Hz, 2H), 7.36–7.38 (d, J = 8.0 Hz, 1H),
7.14–7.16 (d, J = 4.8 Hz, 2H), 2.55 (s, 3H), ppm; LC–MS m/e calcd. for
C26H16Cl2N2O2 458.05, found 459.80.
4-((2-Chloro-6-methoxyquinolin-3-yl)methylene)-2-(4-chlorophenyl)-isoquinoline-
1,3(2H,4H)-dione (3k) Yellow solid; m.p. 242–244 °C; IR (KBr) 1,715 (C3-CO),
1
1,671 (C1-CO) cm-1; H NMR (400 MHz, CDCl3) d 8.29–8.32 (d, J = 4.0 Hz,
2H), 8.07 (s, 1H), 7.96–7.99 (d J = 9.2 Hz, 1H), 7.50–7.52 (m, 2H), 7.43–7.46 (m,
2H), 7.37–7.39 (d, J = 7.2 Hz, 1H), 7.29–7.33 (t, J = 5.6 Hz, 1H), 7.23–7.25 (m,
2H), 6.95–6.96 (d, J = 2.8 Hz, 1H), 3.90 (s, 3H), ppm; 13C NMR (100 MHz,
CDCl3) d 164.93 (C3-CO), 163.87 (C1-CO), 158.73, 146.28, 143.91, 139.44, 136.46,
134.81, 133.66, 133.29, 131.58, 130.01, 129.95, 129.67, 129.62, 128.95, 128.05,
127.82, 126.83, 125.95, 124.41, 105.19,55.71, ppm; LC–MS m/e calcd. for
C26H16Cl2N2O3 474.05, found 475.00.
4-((2-Chloro-7,8-dimethylquinolin-3-yl)methylene)-2-(4-chlorophenyl)-isoquino-
line-1,3(2H,4H)-dione (3l) Greenish-yellow solid; m.p. 198–200 °C; IR (KBr)
1,712 (C3-CO), 1,674 (C1-CO) cm-1; 1H NMR (400 MHz, CDCl3) d 8.29–8.33 (d,
J = 8.4 Hz, 2H), 8.11 (s, 1H), 7.49–7.52 (d, J = 8.8 Hz, 2H), 7.39–7.47 (m, 4H),
7.29 (d, J = 1.2 Hz, 1H), 7.22–7.27 (m, 2H), 2.75 (s, 3H), 2.54 (s, 3H), ppm; 13C
NMR (100 MHz, CDCl3) d 165.01 (C3-CO), 163.91 (C1-CO), 147.87, 147.01,
140.09, 139.78, 138.03, 134.74, 134.32, 133.71, 133.17, 131.71, 130.59, 129.95,
129.85, 129.58, 129.52, 127.60, 127.15, 126.74, 125.91, 125.00, 124.71, 20.86,
13.33, ppm; LC–MS m/e calcd. for C27H18Cl2N2O2 472.07, found 473.00.
4-((2-Chlorobenzo[h]quinolin-3-yl)methylene)-2-(4-chlorophenyl)-isoquinoline-
1,3(2H,4H)-dione (3m) Yellow solid; m.p. [300 °C (charring); IR (KBr) 1,712
(C3-CO), 1,676 (C1-CO) cm-1 1H NMR (400 MHz, CDCl3) d 9.16–9.19 (d,
;
J = 2.8 Hz, 1H), 8.55 (s, 1H), 8.34–8.36 (d, J = 6.4 Hz, 1H), 8.14 (s, 1H),
8.01–8.03 (d, J = 8.0 Hz, 1H), 7.87–7.90 (m, 1H), 7.79–7.83 (m, 2H), 7.70–7.73
(m, 2H), 7.61–7.67 (m, 2H), 7.41–7.43 (d, J = 4.4 Hz, 2H), 7.14–7.16 (d,
J = 4.4 Hz, 2H), ppm; 13C NMR (100 MHz, CDCl3) d 164.02 (C3-CO), 163.06
123

V. Krishnakumar et al.
(C1-CO), 149.19, 147.82, 142.27, 140.16, 139.90, 139.09, 138.97, 134.76, 134.43,
134.40, 133.46, 130.00, 129.67, 129.61, 129.55, 128.07, 127.42, 127.07, 126.66,
124.93, 124.90, 124.66, 124.35, 123.33, ppm; LC–MS m/e calcd. for C29H16Cl2-
N2O2 494.05, found 494.80.
4-(2-Chlorobenzylidene)-2-phenylisoquinoline-1,3(2H,4H)-dione (3n) Greenish-
yellow solid; m.p. 190–192 °C; IR (KBr) 1,721 (C3-CO), 1,674 (C1-CO) cm-1
;
1H NMR (400 MHz, CDCl3) d 7.51–7.55 (m, 3H), 7.42–7.48 (m, 2H), 7.30–7.39
(m, 4H), 7.27–7.29 (m, 3H), 7.23–7.24 (d, J = 0.8 Hz, 2H), ppm; 13C NMR
(100 MHz, CDCl3) d 165.30 (C3-CO), 164.17 (C1-CO), 141.54, 135.41, 134.79,
134.79, 133.75, 132.87, 132.00, 130.57, 130.33, 129.57, 129.37, 129.31, 129.22,
128.71, 128.52, 127.17, 126.98, 125.92, ppm; LC–MS m/e calcd. for C22H14ClNO2
359.07, found 360.00.
Conclusions
An efficient method for montmorillonite-KSF-catalyzed synthesis of 4-[(2-chloro-
quinolin-3-yl)methylene]-N-arylhomophthalimide is reported. The catalyst is reus-
able and inexpensive and offers easy workup and column-free synthesis in shorter
reaction time with high product yield.
Acknowledgments V.K. is grateful to VIT University for their financial assistance as research
associateship. We also acknowledge SIF-VIT and STIC-CUSAT, Cochin for providing NMR facilities.
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