Microwave-assisted solvent-free synthesis of a quinoline-3,4-dicarboximide library on inorganic solid supports

Article abstract of DOI:10.1016/j.tetlet.2004.07.026

Inorganic solid supports are useful media for the rapid and efficient synthesis of a library of quinoline-3,4-dicarboximides. In particular, wet clay K10 was shown to be the best medium for the condensation reaction between 2-methylquinoline-3,4-dicarboxylic anhydride and several primary amines. Microwave irradiation is essential for a rapid and complete conversion.

Full text of DOI:10.1016/j.tetlet.2004.07.026

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 6623–6627
Microwave-assisted solvent-free synthesis of a
quinoline-3,4-dicarboximide library on inorganic solid supports
a,
b
a,b
Annalisa Mortoni,a, Marisa Martinelli, Umberto Piarulli, Nickolas Regalia and
*
*
Stefania Gagliardia
aNiKem Research, Via Zambeletti 25, 20021 Baranzate di Bollate, Milan, Italy
`
Dipartimento di Scienze Chimiche e Ambientali, Universita degli Studi dell’Insubria, Via Valleggio 11, 22100 Como, Italy
b
Received 12 May 2004; revised 5 July 2004; accepted 6 July 2004
Available online 23 July 2004
Abstract—Inorganic solid supports are useful media for the rapid and efficient synthesis of a library of quinoline-3,4-dicarbox-
imides. In particular, wet clay K10 was shown to be the best medium for the condensation reaction between 2-methylquinoline-
3,4-dicarboxylic anhydride and several primary amines. Microwave irradiation is essential for a rapid and complete conversion.
Ó 2004 Elsevier Ltd. All rights reserved.
The increasing need to rapidly provide highly pure small
molecules as potential modulators of therapeutic targets
is driving the development of novel technologies that
can produce compounds at a very high rate. Micro-
wave-assisted organic chemistry is a relatively new tech-
nology that has been shown to significantly improve
productivity in the generation of combinatorial libraries
and complex target molecules.1 In recent years, micro-
wave irradiation has been demonstrated not only to dra-
matically accelerate many organic reactions, but also to
improve yields and selectivity. The impact of micro-
wave-assisted organic synthesis on medicinal chemistry2
is just beginning to be realised, but is clearly evident in
the rapid increase in the number of lectures and pub-
lished articles focusing on the use of this technology to
drive the discovery and optimisation of new leads.
pure product can be obtained directly from the crude
reaction mixture by simple extraction, distillation or
sublimation. In addition solvent-free organic reactions
make synthesis simpler, save energy, and prevent solvent
wastes, hazards and toxicity.
In this letter, we report the results of a preliminary
investigation of a microwave-assisted imide formation4
by the reaction of 2-methylquinoline-3,4-dicarboxylic
anhydride 15 and several primary amines 2 to afford
the corresponding imides 3 (Scheme 1). Many deriva-
tives of 4-quinolinecarboxylic acid have been described
as promising therapeutic agents for the treatment of
various human diseases.6 In a recent paper, 2-methyl-
6-sulfamoylquinoline-3,4-dicarboxylic anhydride was
converted, in low to moderate yields, into the corre-
sponding imide library by refluxing the reagents in tolu-
ene.7 Substantial improvements in imide formation have
been described using microwave irradiation both in
solution8 and in solvent-free conditions.9 The valuable
The coupling of MW irradiation with the use of inor-
ganic supported reagents, under solvent-free condi-
tions,3 provides a chemical process having special
advantages such as enhanced reaction rates, higher
yields, ease of manipulation, the opportunity to work
with open vessels and finally the possibility to upscale
the reaction to multi-gram amounts. Work-up proce-
dures are considerably simplified, as in many cases, the
R
O
O
N
O
O
RNH2 (2a-v)
O
MW, inorganic
N
N
Keywords: Microwave irradiation; Solvent-free synthesis; Solid media;
Quinoline; Imide.
support
3a-v
1
*
Corresponding authors. Tel.: +39-02356947342; fax: +39-023-
56947606 (A.M.); e-mail: annalisa.mortoni@nikemresearch. com
Scheme 1.
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.07.026

6624
A. Mortoni et al. / Tetrahedron Letters 45 (2004) 6623–6627
features of our report include (i) shorter reaction times
and higher yields, (ii) simpler work-up procedures and
(iii) a solvent-free approach to green chemistry.
tions in the presence of silica gel as inorganic solid
support.
Although the use of inorganic solid supports in combi-
nation with microwave irradiation is well docu-
mented,3,10 no examples of imide formation on solid
support without the addition of a strong Lewis acid have
been reported so far. Best yields were obtained when a
mixture of anhydride 1 and silica gel were ground in a
mortar until a homogeneous powder was formed. One
equivalent of primary amines 2a–v was then added and
the residue irradiated in the microwave oven at 150°C
for 15min. The reaction mixture was finally transferred
on the top of a cartridge filled with silica gel and the final
Our first aim was to develop an improved procedure for
the preparation of a set of imides starting from the cor-
responding dicarboxylic anhydride. As a starting point,
we studied the microwave-assisted condensation
between the quinoline anhydride (1) and pentylamine
(2a) in toluene (Table 1, entry 2). The solution was
heated to 150°C for 30min in a sealed vessel. Com-
pound 3a was isolated in high yield and purity, after
evaporation of toluene and basic washing. We further
investigated the same reaction using solvent-free condi-
Table 1. Condensation of 2-methylquinoline-3,4-dicarboxylic anhydride with primary amines
O
NH2
NH2
NH2
NH2
N
N
N
NH2
NH2
S
NH2
MeO
H2N
HN
NH2
N
O
2a
NH2
2h
2g
2f
2e
2b
2c
2d
NH2
OMe
N
NH2
NH2
NH2
NH2
NH2
2i
2j
2k
2r
2l
2m
2n
2o
NH2
NH2
HCl
NH2
H2N
N
COOH
H2N
NH2
S
N
H
S
O
O
2t
2p
2q
2s
2u
2v
Entry
Amine
Conditions (temperature/time)
Methoda
Product (%)
1
2a
2a
2b
2c
2d
2d
2e
2f
150°C/15min
150°C/ 30min
150°C/15min
150°C/15min
150°C/15min
150°C/120min
150°C/15min
150°C/15min
150°C/15min
150°C/15min
150°C/15min
150°C/90min
150°C/15min
150°C/30min
150°C/30min
150°C/30min
150°C/30min
150°C/30min
150°C/75min
150°C/120min
150°C/120min
150°C/20min
180°C/15min
180°C/120min
150°C/ 15min
180°C/120min
150°C/15min
A
B
3a (95,b 80c)
3a (90,b 78c)
3b (>95,b 75c)
3c (>95,b 65c)
3d (90b)
2
3
A
A
A
B
4
5
6
3d (90b)
7
A
A
A
A
A
B
3e (>95b)
3f (>95b)
8
9
2g
2h
2i
3g (>95b)
3h (>95,b 65c)
3i (95b)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
2i
3i (90b)
3j (>95b)
2j
A
A
A
A
A
A
A
A
A
A
B
2k
2l
3k (>95b)
3l (>95,b 70c)
3m (75b, 60c)
3n (>95b)
3o (>95b)
3p (>95b, 70c)
3q (––)
2m
2n
2o
2p
2q
2r
2s
2s
2t
3r (––)
3s (60b)
3s (40b)
B
3t (80b)
2u
2u
2v
A
B
3u (90,b 72c)
3u (85b)
A
3v (75,b 60c)
a Method A: anhydride (0.5mmol), amine (1equiv), SiO2 (250mg); method B: anhydride (0.5mmol), amine (1equiv), toluene (4mL).
b Conversion of 1 in 3a–v determined by LC-MS analysis of the crude reaction mixtures.
c Isolated yield after crystallisation (purity >98%).

A. Mortoni et al. / Tetrahedron Letters 45 (2004) 6623–6627
6625
product was separated from the more polar by-products
by elution with a mixture of DCM/MeOH.11
ferent reaction times (15, 30 and 75min, respectively,
method A, Table 1) and one (2r) that did not afford
any product after heating for 2h, were selected to inves-
tigate other reaction media. Among the possible inor-
ganic supports, Al2O3 (neutral, acidic and basic) and
montmorillonite K10 were considered. For all the experi-
ments in Table 2, the temperature and the reaction time
were fixed at 150°C and 15min. Among the various
inorganic media tested, the best results were obtained
with clay K10, which afforded complete conversions,
also with amines showing low reactivity on silica (Table
2, entries 3 and 4). Moreover, we found that the use of
commercial montmorillonite led to complete conver-
sions, which were not obtained when vacuum-dried
montmorillonite12 was used (Table 2). This effect could
be due to the presence of an unquantified amount of
water that strongly interacts with the microwaves and
increases the medium capability to absorb the micro-
wave energy.
These conditions were applied for the preparation of a
library of N-substituted 4-methyl-pyrrolo[3,4-c]quino-
line-1,3-diones. The procedure proved to be optimal
for a wide variety of primary amines and the results in
Table 1 show that conversions for almost all the 22 imi-
des 3 are very high. Moreover, even without any addi-
tional purification, the HPLC purities were typically
80–95%, which is usually sufficient for primary biologi-
cal screening.
The reaction times varied from 15min to 2h, with only
adamantan-1-yl-methylamine (2q) and cyclohexyl-ethyl-
amine (2r) showing no formation of the desired products
even when the heating was prolonged for 2h.
While the conversion yields obtained by applying meth-
ods A or B were comparable, the reaction times were
shorter when a solid support was used (Table 1, entries
1, 5, 11, 22 and 25 vs 2, 6, 12, 23 and 26). Furthermore,
the work-up of these solvent-free reactions was simpler
and could be easily transferred to an automated
approach.
In order to evaluate the synergy between the inorganic
solid support and microwave irradiation, parallel experi-
ments both with microwave-assisted and conventional
heating were carried out (Table 3).
Conversions obtained by microwave heating were higher
than those gained warming the reactions in an oil bath.
Different hypotheses have been proposed to account for
the observed rate enhancement under microwave irradi-
ation.3a,13 It is noteworthy that mineral oxides are often
very poor conductors of heat. Using conventional oil
bath, heating is difficult and nonhomogeneous with
large temperature gradient and overheating on the vessel
walls. By contrast they behave as very efficient micro-
wave absorbents and this led to a very rapid and homo-
geneous heating. Improvement in temperature
homogeneity and heating rates imply faster reactions
when compared with those obtained in classical
conditions.
We further investigated the condensation reaction on sil-
ica gel with solid amines having melting points both
lower (entry 22, tryptamine, mp: 119°C) or higher (entry
27, b-alanine, mp: 202°C) than the reaction tempera-
ture. It has been reported9a that solvent-free microwave
reactions between phthalic anhydride and amines need
at least one liquid phase. Therefore, reactions between
two solids may not take place and require the use of a
high boiling solvent. In our case, when the solid amine
2v was reacted with quinoline anhydride 1 (mp
200°C), the desired imide 3v was obtained in good yield
and purity (Table 1, entry 27). This unexpected result
can probably be ascribed to an effective higher tempera-
ture inside the reaction vessels.
In conclusion, we have demonstrated the utility of inor-
ganic solid supports as reaction media for imide forma-
tion. In particular ÔwetÕ montmorillonite14 K10 seems to
be the favoured solid support for this kind of reaction.
The protocol is convenient and environmentally
In order to further optimise the reaction conditions and
the purity of the resulting imides, we investigated the use
of inorganic supports other than silica. For this reason
three amines (2i, 2l, 2p), selected on the basis of their dif-
Table 2. Imide formation with a reaction time of 15min using different inorganic solid supports
Entry
Amine
Neat
SiO2
Al2O3 neutral
Al2O3 acidic
Al2O3 basic
Clay K10
Dried clay K10
1
2
3
4
2i
3i (55%)
3l (80%)
3p (5%)
3r (––)
3i (95%)
3l (20%)
3p (5%)
3r (––)
3i (85%)
3l (77%)
3p (90%)
3r (60%)
3i (65%)
3l (30%)
3p (90%)
3r (73%)
3i (73%)
3l (40%)
3p (95%)
3r (50%)
3i (90%)
3i (80%)
3l (60%)
3p (95%)
3r (58%)
2l
3l (100%)
3p (100%)
3r (100%)
2p
2r
Conversions determined by LC-MS.
Table 3. Comparison between microwave-assisted and conventional heating
Ex.
Amine
Solid support
Producta (%) MW
Producta (%) convent. heat.
1
2
3
4
2i
SiO2
3i (95)
3i (25)
3l (50)
3p (––)
3r (––)
2l
Clay K10
Al2O3
Clay K10
3l (100)
3p (90)
3r (100)
2p
2r
a Conversions determined by LC-MS after 15min at 150°C.

6626
A. Mortoni et al. / Tetrahedron Letters 45 (2004) 6623–6627
H. C.; Andersson, C. Tetrahedron Lett. 2000, 41,
7947–7950; (c) Loghmani-Khouzani, H.; Sadeghi, M.
M.; Safari, J.; Minaeifar, A. Tetrahedron Lett. 2001, 42,
4363–4364.
friendly. We have also shown that microwave irradia-
tion is essential for rapid and high yielding reactions.
Acknowledgements
11. Typical experimental procedure for preparation of imides
on inorganic solid support: the quinolineanhydride (1)
(100mg, 0.47mmol) was mechanically dispersed on inor-
ganic solid support (250mg) in a 10mL microwave vial.
Then amine was added (0.47mmol). The vial was sealed
with a crimped cap and was placed in a CEM Discover
microwave apparatus. The initial power supplied was
150W; once the temperature reached 150°C, the instru-
ment adjusted the power to maintain constant tempera-
ture. Heating time at 150°C was 15min. After completion
of the reaction, a mixture 1/1 of DCM/methanol was
added to the reaction mixture, inorganic solid support was
filtered and the final product recovered after solvent
evaporation. Compound 3a: Solid, mp: 77–78°C, 1H
NMR (DMSO-d6, 300MHz): d 8.67 (d, J = 8.2Hz, 1H),
8.08 (d, J = 8.2Hz, 1H), 7.94 (td, J = 8.2 and 1.3Hz, 1H),
7.79 (td, J = 8.2 and 0.6Hz, 1H), 3.60 (t, J = 6.9Hz, 2H),
2.90 (s, 3H), 1.63–1.54 (m, 2H), 1.38–1.22 (m, 4H), 0.87 (t,
J = 6.9Hz, 3H). 13C NMR (DMSO-d6, proton decoupled):
d 168.1, 167.9, 154.1, 150.5, 135.6, 132.4, 128.9, 128.8,
124.0, 122.0, 119.8 37.4, 28.8, 28.3, 21.5 (2C), 13.6. MS:
m/z: 283 M+. Elemental analysis: calcd for C17H18O2N2
(282.345): C, 72.32; H, 6.43; N, 9.92; found: C, 72.12; H,
6.23; N, 9.98. Compound 3b: Solid, 1H NMR (DMSO-d6,
300MHz): d 8.64 (d, J = 8.2Hz, 1H), 8.08 (d, J = 8.2Hz,
1H), 7.95 (dd, J = 8.2 and 7.3Hz, 1H), 7.79 (dd, J = 8.2
and 7.2Hz, 1H), 3.71 (t, J = 6.3Hz, 2H), 2.91 (s, 3H), 2.54
(t, J = 6.3Hz, 2H), 2.21 (s, 6H). 13C NMR (DMSO-d6,
proton decoupled): d 168.0, 167.8, 154.1, 150.5, 135.5,
132.5, 128.9, 128.8, 124.0, 121.9, 119.8, 56.3, 44.9 (2C),
35.5, 21.5. MS: m/z: 284 M+. Compound 3c: Solid, 1H
NMR (DMSO-d6, 300MHz): d 8.67 (d, J = 8.2Hz, 1H),
8.03 (d, J = 8.2Hz, 1H), 7.94 (td, J = 8.2 and 1.6Hz, 1H),
7.79 (td, J = 8.2 and 1.3Hz, 1H), 2.90 (s, 3H), 2.69 (m,
1H), 0.99–0.91 (m, 4H). 13C NMR (DMSO-d6, proton
decoupled): d 168.5, 168.4, 154.1, 150.4, 135.2, 132.4,
128.9, 128.8, 124.0, 121.7, 119.8, 21.5, 20.4, 4.7 (2C). MS:
m/z: 253 M+. Compound 3d: Solid, 1H NMR (DMSO-d6,
300MHz): d 8.69 (d, J = 8.2Hz, 1H), 8.13 (d, J = 8.2Hz,
1H), 7.96 (td, J = 8.2 and 1.6Hz, 1H), 7.83 (td, J = 8.2 and
1.3Hz, 1H), 4.61 (tt, J = 13.2 and 3.2Hz, 1H), 2.98 (s, 3H),
2.44 (dd,J = 13.2 and 13.2Hz, 2H), 1.90 (dd, J = 13.2 and
3.2Hz, 2H), 1.50 (s, 6H), 1.45 (s, 6H). 13C NMR (DMSO-
d6, proton decoupled): d 167.9, 167.8, 154.1, 150.5, 135.4,
132.6, 129.0, 128.9, 123.9, 121.8, 119.9, 41.7 (2C), 37.3,
29.9 (2C), 23.9 (4C), 21.5. MS: m/z: 352 M+. Compound
3e: Solid, 1H NMR (DMSO-d6, 300MHz): d 8.68 (d,
J = 8.2Hz, 1H), 8.12 (d, J = 8.2Hz, 1H), 7.97 (t,
J = 8.2,Hz, 1H), 7.82 (t, J = 8.2,Hz, 1H), 3.71 (t,
J = 6.6Hz, 2H), 3.25–3.05 (m, 6H), 2.93 (s, 3H), 2.05 (m,
2H), 1.93–180 (m, 2H), 1.72–154 (m, 2H). 13C NMR
(DMSO-d6, proton decoupled): d 168.2, 168.0, 154.1,
150.5, 135.8, 132.6, 129.0, 128.9, 124.1, 122.2, 119.9, 52.8
(2C), 51.5, 34.9, 24.6, 22.6 (2C), 21.5. MS: m/z: 324 M+.
We wish to thank Dr. Alberto Cerri for analytical
support.
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1
Compound 3f: Solid, H NMR (DMSO-d6, 300MHz): d
8.68 (d, J = 8.2Hz, 1H), 8.11 (d, J = 8.2Hz, 1H), 7.96 (td,
J = 8.2 and 1.6Hz, 1H), 7.81 (td, J = 8.2 and 1.3Hz, 1H),
3.74 (t, J = 6.6Hz, 2H), 3.51 (dd, J = 4.7 and 4.7Hz, 4H),
2.92 (s, 3H), 2.57 (t, J = 6.6Hz, 2H), 2.44 (dd, J = 4.7 and
4.7Hz, 4H). 13C NMR (DMSO-d6, proton decoupled): d
168.0, 167.8, 154.1, 150.5, 135.6, 132.6, 129.0, 128.9, 124.0,
122.0, 119.9, 66.1 (2C), 55.4, 53.0 (2C), 34.7, 21.5. MS: m/
z: 326 M+. Compound 3g: Solid, 1H NMR (DMSO-d6,
300MHz): d 8.65 (d, J = 8.2Hz, 1H), 8.12 (d, J = 8.2Hz,
1H), 7.97 (td, J = 8.2 and 1.25Hz, 1H), 7.57 (td, J = 8.1
´
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A. Mortoni et al. / Tetrahedron Letters 45 (2004) 6623–6627
6627
and 1.25Hz, 1H), 7.59 (s br, 1H), 6.47–6.39 (m, 2H), 4.80
(s, 2H), 2.95 (s, 3H). 13C NMR (DMSO-d6, proton
decoupled): d 167.3, 167.2, 154.3, 150.5, 149.1, 142.6,
135.5, 132.6, 129.0, 128.9, 124.0, 122.0, 119.9, 110.5, 108.2,
34.1, 21.6. MS: m/z: 293 M+. Compound 3h: Solid, 1H
NMR (DMSO-d6, 300MHz): d 8.69 (d, J = 8.2Hz, 1H),
8.12 (d, J = 8.2Hz, 1H), 7.96 (td, J = 8.2 and 1.6Hz, 1H),
7.82 (td, J = 8.2 and 1.3Hz, 1H), 3.51 (d, J = 7.2Hz, 2H),
2.93 (s, 3H), 1.21–1.05 (m, 1H), 0.55–0.33 (m, 4H). 13C
NMR (DMSO-d6, proton decoupled): d 168.5, 168.4,
154.2, 150.5, 135.3, 132.5, 128.9, 128.8, 124.1, 122.0, 119.9,
41.9, 21.6, 10.0, 3.6 (2C). MS: m/z: 267 M+. Compound 3i:
167.2, 154.3, 150.5, 138.1, 125.5, 132.6, 129.0, 128.9, 127.1,
126.8, 126.1, 124.0, 121.9, 119.8, 35.6, 21.6. MS: m/z: 309
M+. Compound 3p: Solid, 1H NMR (DMSO-d6,
300MHz): d 8.80 (d, J = 8.2Hz, 1H), 8.02 (d, J = 8.2Hz,
1H), 7.85 (td, J = 8.2 and 1.6Hz, 1H), 7.79 (td, J = 8.2 and
0.9Hz, 1H), 3.45 (d, J = 6.6Hz, 2H), 2.91 (s, 3H), 1.79–
1.51 (m, 6H), 1.26–1.08 (m, 3H), 1.06–0.89 (m, 2H). 13C
NMR (DMSO-d6, proton decoupled): d 168.3, 168.1,
154.1, 150.5, 135.5, 132.4, 128.9, 128.8, 124.1, 122.0, 119.9,
43.5, 36.4, 30.1 (2C), 25.7, 25.1 (2C), 21.5. MS: m/z: 309
M+. Elemental analysis: calcd for C19H20O2N2 (308.383):
C, 74.00; H, 6.54; N, 9.08; found: C, 73.88; H, 6.13; N,
10.03. Compound 3r: Solid, 1H NMR (DMSO-d6,
300MHz): d 8.69 (d, J = 8.5Hz, 1H); 8.10 (d, J = 8.5Hz,
1H); 7.95 (td, J = 8.5 and 1.3Hz, 1H); 7.80 (td, J = 8.5 and
1.3Hz, 1H); 3.95 (m, 1H); 2.92 (s, 3H); 2.03–1.82 (m, 2H);
1.73 (m, 1H); 1.59 (m, 2H); 1.44 (d, J = 6.9Hz, 3H); 1.32–
0.76 (m, 6H). 13C NMR (DMSO-d6, proton decoupled): d
168.3, 168.1, 154.2, 150.0, 135.1, 132.4, 128.9, 128.8, 124.1,
121.7, 119.9, 51.7, 29.8 (2C), 28.5 (2C), 25.6, 25.3, 21.5,
15.8. MS: m/z: 323 M+. Elemental analysis: calcd for
C20H22O2N2 (322.411): C, 75.51; H, 6.88; N, 8.69;
found: C, 75.16; H, 6.73; N, 8.73. [a]D = + 12.5, (c=1,0
MeOH). Compound 3s: Solid, 1H NMR (DMSO-d6,
300MHz): d 10.82 (s br, 1H), 8.68 (d, J = 8.2Hz, 1H),
8.11 (d, J = 8.2Hz, 1H), 7.96 (td, J = 8.2 and 1.3Hz, 1H),
7.81 (td, J = 8.2 and 0.9Hz, 1H), 7.60 (d, J = 7.9Hz, 1H),
7.34 (d, J = 7.9Hz, 1H), 7.23 (d, J=2.5Hz, 1H), 7.06 (td,
J = 7.9 and 0.9Hz, 1H), 6.98 (td, J = 7.9 and 1.3Hz, 1H),
Solid, 1H NMR (DMSO-d6, 300MHz):
d 8.66 (d,
J = 8.2Hz, 1H), 8.08 (d, J = 8.2Hz, 1H), 7.94 (td, J = 8.2
and 1.6Hz, 1H), 7.79 (td, J = 8.2 and 1.3Hz, 1H), 4.02 (tt,
J = 12.0 and 3.8Hz, 1H), 2.90 (s, 3H), 2.19–2.00 (m, 2H),
1.89–1.61 (m, 5H), 1.44–1.10 (m, 3H). 13C NMR (DMSO-
d6, proton decoupled): d 168.0, 167.8, 154.1, 150.4, 135.3,
132.4, 128.9, 128.8, 124.0, 121.8, 119.8, 50.2, 29.3 (2C),
25.4 (2C), 24.8, 21.5. MS: m/z: 295 M+. Elemental
analysis: calcd for C18H18O2N2 (294.356): C, 73.45; H,
6.16; N, 9.52; found: C, 73.36; H, 6.12; N, 9.58.
1
Compound 3j: Solid, H NMR (DMSO-d6, 300MHz): d
8.64 (d, J = 8.2Hz, 1H), 8.09 (d, J = 8.2Hz, 1H), 7.96 (td,
J = 8.2 and 1.3Hz, 1H), 7.80 (td, J = 8.2 and 0.9Hz, 1H),
4.69 (t, J = 5.7Hz, 1H), 3.71 (d, J = 5.7Hz, 2H), 3.32 (s,
6H), 2.91 (s, 3H) 13C NMR (DMSO-d6, proton decou-
pled): d 167.7, 167.5, 154.2, 150.5, 135.3, 132.6, 129.0,
128.9, 124.0, 121.8, 119.7, 100.1, 53.2, 38.6 (2C), 21.5. MS:
m/z: 301 M+. Compound 3k: Solid, 1H NMR (DMSO-d6,
300MHz): 8.76 (d, J = 8.2Hz, 1H), 8.10 (d, J = 8.2Hz,
1H), 7.96 (td, J = 8.2 and 1.6Hz, 1H), 7.81 (td, J = 8.2 and
1.3Hz, 1H), 7.40–7.23 (m, 5H), 4.82 (s, 2H), 2.92 (s, 3H).
13C NMR (DMSO-d6, proton decoupled): d 167.9, 167.8,
154.3, 150.5, 136.3, 135.5, 132.6, 128.9, 128.8, 128.4 (2C),
127.4 (2C), 127.3, 124.1, 122.1, 119.9, 40.9, 21.6. MS: m/z:
303 M+. Compound 3l: Solid, 1H NMR (DMSO-d6,
300MHz): d 8.64 (d, J = 8.2Hz, 1H), 8.10 (d, J = 8.2, 1H),
7.96 (td, J = 8.2 and 1.3Hz, 1H), 7.80 (td, J = 8.2 and
1.3Hz, 1 H), 7.31–7.16 (m, 5H), 3.85 (m, 2H), 2.96 (m,
2H), 2.91 (s, 3H). 13C NMR (DMSO-d6, proton decou-
pled): d 167.9, 167.6, 154.1, 150.5, 138.1, 135.5, 132.6,
129.0, 128.8, 128.5 (2C), 128.4 (2C), 126.3, 124.0, 121.9,
119.8, 33.6 (2C), 21.5. MS: m/z: 317 M+. Elemental
analysis: calcd for C20H16O2N2 (316.363): C, 75.93; H,
5.10; N, 8.85; found: C, 75.78; H, 5.95; N, 8.90.
Compound 3m: Solid, 1H NMR (DMSO-d6, 300MHz):
d 8.67 (d, J = 8.2Hz, 1H), 8.10 (d, J = 8.2Hz, 1H), 7.95 (t
br, J = 8.2Hz, 1H), 7.79 (t br, J = 8.2Hz, 1H), 7.46 (d br,
J = 7.6Hz, 2H), 7.35 (m, 2H), 7.27 (m, 1H), 5.50 (q,
J = 7.55, 1H), 2.91 (s, 3H), 1.87 (d, J = 7.55Hz, 3H). 13C
NMR (DMSO-d6, proton decoupled): d 167.9, 167.8,
154.2, 150.5, 140.3, 135.3, 132.5, 128.9, 128.8, 128.3 (2C),
127.2, 126.6 (2C), 124.0, 121.8, 119.9, 48.8, 21.5, 17.4. MS:
m/z: 317 M+ [a]D + 41.5, (c 1.0 CHCl3). Compound 3n:
3.88 (m, 2H), 3.07 (m, 2H), 2.92 (s, 3H).
d
13C
NMR (DMSO-d6, proton decoupled): d 168.0, 167.8,
154.1, 150.5, 136.2, 135.7, 132.5, 128.9, 128.8, 126.9,
124.1, 122.9, 122.1, 120.9, 119.9, 118.3, 117.8, 111.4,
110.5, 38.3, 23.8, 21.5. MS: m/z: 356 M+. Compound 3t:
Solid, 1H NMR (DMSO-d6, 300MHz):
d 8.69 (d,
J = 8.2Hz, 1H), 8.12 (d, J = 8.2Hz, 1H), 7.97 (td, J = 8.2
and 1.3Hz, 1H), 7.82 (td, J = 8.2 and 1.3Hz, 1H), 3.76 (d,
J = 6.9Hz, 2H), 3.46–2.98 (m, 4H), 2.93 (s, 3H), 2.84–2.68,
(m, 1H), 2.29 (m, 1H), 2.00–1.83 (m, 1H). 13C NMR
(DMSO-d6, proton decoupled): d 168.2, 167.9, 154.1,
150.4, 135.8, 132.5, 128.9, 128.8, 124.1, 122.2, 119.9, 53.9,
51.1, 38.6, 35.4, 25.8, 21.5. MS: m/z: 345 M+. Compound
3u: Solid, 1H NMR (DMSO-d6, 300MHz): d 8.67 (d,
J = 8.2Hz, 1H), 8.13 (d, J = 8.2Hz, 1H), 7.98 (td, J = 8.2
and 1.6Hz, 1H), 7.83 (td, J = 8.2 and 1.2Hz, 1H), 7.23 (q,
J = 0.9Hz, 1H), 5.74 (s, 2H), 2.94 (s, 3H), 2.31 (d,
J = 0.9Hz, 3H). 13C NMR (DMSO-d6, proton decoupled):
d 167.3, 167.2, 163.4, 154.4, 151.7, 150.6, 135.5, 132.8,
129.2, 128.9, 124.1, 121.9, 119.8, 115.0, 38.6, 21.6, 16.5.
MS: m/z: 324 M+. Compound 3v: Solid, 1H NMR
(DMSO-d6, 300MHz): d 8.66 (d, J = 8.2Hz, 1H), 8.10 (d,
J = 8.2Hz, 1H), 7.96 (dd, J = 8.2 and 6.6Hz, 1H), 7.80
(dd, J = 8.2 and 6.6Hz, 1H), 3.84 (t, J = 7.2Hz, 2H), 2.91
(s, 3H), 2.66 (t, J = 7.2Hz, 2H). 13C NMR (DMSO-d6,
proton decoupled): d 171.9, 167.8, 167.6, 154.1, 150.5,
135.6, 132.5, 129.0, 128.8, 124.0, 122.0, 119.8, 33.5, 32.2,
21.5. MS: m/z: 285 M+. Elemental analysis: calcd for
C15H12N2O4 (284.274): C, 63.38; H, 4.25; N, 9.85; found:
C, 62.89; H, 4.36; N, 9.98.
Solid, 1H NMR (DMSO-d6, 300MHz):
d 8.60 (d,
J = 8.2Hz, 1H), 8.05 (d, J = 8.2Hz, 1H), 7.93 (t,
J = 8.2Hz, 1H), 7.77 (t, J = 8.2Hz, 1H), 7.63 (s br, 1H),
7.19 (s br, 1H), 6.86 (s br, 1H), 4.06 (t, J = 6.9Hz, 2H),
3.59 (t, J = 6.9Hz, 2H), 2.87 (s, 3H), 2.09 (m, 2H). 13C
NMR (DMSO-d6, proton decoupled): d 168.1, 167.9,
154.0, 150.4, 137.2, 135.6, 132.4, 128.8, 128.7, 128.2, 124.0,
122.0, 119.8, 119.1, 43.5, 34.9, 29.4, 21.5. MS: m/z: 321
M+. Compound 3o: Solid, 1H NMR (DMSO-d6,
300MHz): d 8.64 (d, J = 8.2Hz, 1H), 8.07 (d, J = 8.2Hz,
1H), 7.93 (td, J = 8.2 and 1.6Hz, 1H), 7.78 (td, J = 8.2 and
1.3Hz, 1H), 7.45 (dd, J = 5.0 and 1.3Hz, 1H), 7.15 (m,
1H), 6.98 (dd, J = 5.0 and 3.5Hz, 1H), 4.97 (s, 2H), 2.90 (s,
3H). 13C NMR (DMSO-d6, proton decoupled): d 167.4,
12. Commercial montmorillonite K10 was dried under vac-
uum at 100°C till constant weight was observed.
13. (a) Loupy, A.; Perreux, L. Tetrahedron 2001, 57,
9199–9223; (b) Kuhnert, N. Angew. Chem., Int. Ed.
2002, 41, 1863–1866; (c) Garbacia, S.; Desai, B.; Lavastre,
O.; Kappe, O. J. Org. Chem. 2003, 68, 9136–9139; (d)
Leadbeater, N. E.; Marco, M. J. Org. Chem. 2003, 68,
888–892.
14. Commercial montmorillonite can be used directly as Ôwet
montmorillonite K10Õ.