Efficient and direct synthesis of poly-substituted indeno1[1,2-b]quinolines assisted by p-toluene sulfonic acid using high-temperature water and microwave heating via one-pot, three-component reaction

Article abstract of DOI:10.1039/b611462h

Reactions of aldehydes, 1,3-indanedione and enaminones were successfully carried out using p-toluene sulfonic acid (p-TsOH) as a catalyst and high-temperature water as a solvent under microwave irradiation. This method provided several advantages such as

Full text of DOI:10.1039/b611462h

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PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Efficient and direct synthesis of poly-substituted indeno[1,2-b]quinolines
assisted by p-toluene sulfonic acid using high-temperature water and
microwave heating via one-pot, three-component reaction†
Shu-Jiang Tu,* Bo Jiang, Jun-Yong Zhang, Run-Hong Jia, Yan Zhang and Chang-Sheng Yao
Received 8th August 2006, Accepted 12th September 2006
First published as an Advance Article on the web 29th September 2006
DOI: 10.1039/b611462h
Reactions of aldehydes, 1,3-indanedione and enaminones were successfully carried out using p-toluene
sulfonic acid (p-TsOH) as a catalyst and high-temperature water as a solvent under microwave
irradiation. This method provided several advantages such as rapid reaction times, high yields, and a
simple workup procedure. In addition, a possible mechanism to account for the reaction was proposed.
To our delight, we found that this reaction can be successfully
Introduction
carried out in aqueous media, and a series of enaminones derived
The similar polarity of classic organic solvents and high-
from various amines such as cyclopropanamine, methylamine,
temperature water has aroused much interest in the investigation of
aminoacetic acid, and aromatic amines can take part in this
organic transformations in aqueous media.1 In addition to being a
reaction.
safe, readily available and environmentally friendly solvent,2 water
p-Toluene sulfonic acid (p-TsOH), an easily available and cheap
has also been recognized as an effective reaction medium with
reagent has been used as an acidic catalyst in the synthesis
unique properties and possibilities for many organic reactions.3
Simultaneously, high density microwave irradiation has matured
into a reliable and useful methodology for accelerating small-
scale reactions.4 Thus, it has become clear that the combined
approach of microwave superheating, homogeneous catalysis, and
an aqueous medium offers a nearly synergistic strategy in the sense
that the combination in itself offers greater potential than the three
parts in isolation.5
In modern drug discovery a number of solutions to increase
the output of unique chemical entities have been presented, e.g.,
combinatorial synthesis, parallel synthesis, and automated library
production.6 Even though many of these small-scale techniques
are productive, they generate significant quantities of chemical
waste.7 Overall, the development of new methods with reduced
environmental impact is of increasing importance. The use of water
as a nontoxic reaction medium, together with the employment of
energy-efficient microwave heating8 and catalytic methods, must be
considered to be both promising and enabling green alternatives.
Indenoquinoline derivatives are important heterocyclic com-
pounds, which exhibit a diverse range of biological properties
such as 5-HT-receptor binding activity9 and anti-inflammatory
activity.10 They also act as antitumor agents,11 steroid reductase
inhibitors,12 acetylcholinesterase inhibitors,13 antimalarials14 and
new potential topo I/II inhibitors.15 Therefore, the synthesis of
this type of compounds has attracted considerable attention.16 In
our previous communication,17 we accomplished the construction
of the indeno[1,2-b]quinoline scaffold in HOAc with aryl groups
being introduced to the nitrogen atom in indeno[1,2-b]quinoline.
of a variety of heterocyclic compounds.18 However, the use p-
TsOH as a catalyst in aqueous media for the synthesis of poly-
substituted indeno[1,2-b]quinolines and their derivatives has not
been reported. In this paper, we wish to report a general and highly
efficient synthesis of poly-substituted indeno[1,2-b]quinolines,
using p-TsOH as a catalyst, from various enaminones under
microwave irradiation. This is an efficient synthesis in aqueous
media, which not only preserves the simplicity of the reaction
but also consistently gives the corresponding products in good to
excellent yields (Scheme 1).
Scheme 1 Synthetic route to indeno[1,2-b]quinoline derivatives.
Result and discussion
3-(Cyclopropylamino)-5,5-dimethylcyclohex-2-enone 3a has been
used as the starting material to synthesize poly-substituted
indeno[1,2-b]quinolines. We therefore first chose 3a and
searched for the optimized conditions for its reaction with p-
chlorobenzaldehyde 1a and 1,3-indanedione 2 affording poly-
substituted indeno[1,2-b]quinolines under microwave conditions
(microwave oven EmrysTM Creator from Personal Chemistry,
Uppsala, Sweden) (Scheme 2).
Department of Chemistry, Xuzhou Normal University, Key Laboratory of
Biotechnology for Medicinal Plants, Xuzhou, Jiangsu, 211116, P. R. China.
E-mail: laotu@xznu.edu.cn; Fax: +86(516) 83403164; Tel: +86(516)
83500349
† Electronic supplementary information (ESI) available: Characterization
data for compounds 4a–t and 4x–z. See DOI: 10.1039/b611462h
Different acidic catalysts were examined first. The results of
these comparative experiments are summarized in Table 1. From
the results it is obvious that p-TsOH (entry 1) demonstrates
superior catalytic activity and is the best catalyst among those
examined. In order to further evaluate the influence of p-TsOH
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Table 2 Optimization of the amount of p-TsOH in the synthesis of
compound 4a at 150 ◦C under microwave irradiation
Entry
p-TsOH/eq.
Time/min
Yield (%)
1
2
3
4
5
6
7
8
0.1
0.3
0.6
0.8
0.9
1.0
1.2
1.4
3
3
3
3
3
3
3
3
79
84
89
90
91
93
91
92
Scheme 2 Optimization of the catalyst in the synthesis of compound 4a.
Table 1 Optimization of the catalyst in the synthesis of compound 4a in
highest yield (entry 6). Further increases in the amount of catalyst
did not improve the yield (entries 7–8).
water at 150 ◦C under microwave irradiation
We therefore selected 1.0 equivalent of p-TsOH as the catalyst
for further study. At the beginning of the search for the aldehyde
substrate scope, enaminone 3a and 1,3-indanedione were used as
model substrates (Table 3, entries 1–4), and the results indicated
that aromatic aldehydes bearing either electron donating or elec-
tron withdrawing functional groups such as nitro, chloro, hydroxy,
or methoxy were able to effect the synthesis of compounds 4. We
also observed delicate electronic effects: that is, aryl aldehydes
with electron-withdrawing groups (Table 3, entries 1–2) reacted
rapidly, while substitution of electron-rich groups (Table 3, entry
3) on the benzene ring decreased the reactivity, requiring longer
reaction times.
To expand the scope of enaminone substrates, we used different
aldehydes and 1,3-indanedione as model substrates and examined
various enaminones including 3b, 3c, 3d, 3e and 3f. In all these
cases, the reactions proceeded smoothly to give the corresponding
indeno[1,2-b]quinoline-9,11(6H,10H)-diones in good yields of
86–94%. Moreover, the heterocyclic aldehydes such as thiophene-
2-carbaldehyde (Table 3, entries 8, 19 and 23), and aliphatic
aldehydes such as 2-phenylacetaldehyde (Table 3, entry 20) still
Entry
Catalyst
Time/min
Yield (%)
1
2
3
4
5
6
7
8
p-TsOH
L-Proline
Silica sulfuric acid
KH2PO4
KHSO4
HCl
H2SO4
3
3
3
3
3
3
3
3
93
76
68
79
81
56
49
72
H3PO4
concentration, this reaction was carried out using different
amounts of p-TsOH under microwave irradiation. The results are
listed in Table 2.
From Table 2 it can be seen that the reaction proceeded in the
presence of 0.1 equivalents of p-TsOH to give the product 4a in
79% yield under microwave irradiation at 150 ◦C after 3 minutes
of reaction (entry 1). Increasing the amount of catalyst to 0.3, 0.6,
0.8 and 0.9 equivalents successively resulted in the increasing of
the yield to 84%, 89%, 90% and 91%, respectively. Use of just 1.0
equivalent under microwave irradiation was sufficient to reach the
Table 3 The synthesis of compounds 4 using p-TsOH as catalyst in aqueous media under microwave irradiation
Entry
R
3
R1
R2
4
Time/min
Yield (%)a
Mp/◦C
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
4-ClC6H4 (1a)
3a
3a
3a
3a
3b
3b
3b
3c
Cyclopropyl
Cyclopropyl
Cyclopropyl
Cyclopropyl
CH2COOH
CH2COOH
CH2COOH
CH3
CH3
CH3
H
H
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
H
4a
4b
4c
4d
4e
4f
4g
4h
4i
3
2
5
3
6
4
3
5
5
3
5
4
6
4
7
5
3
5
6
7
6
3
6
93
94
89
93
89
92
93
87
90
92
89
94
89
90
87
88
92
89
86
89
91
94
87
295–297
268–270
220–222
245–247
257–259
239–240
248–250
232–234
230–233
228–230
282–284
>300
276–278
295–297
274–276
283–28517
255–25617
257–25917
267–269
207–209
250–25117
236–23717
230–23217
4-NO2C6H4 (1b)
4-CH3OC6H4 (1c)
4-OH-3-NO2C6H3 (1d)
C6H5 (1e)
4-FC6H4 (1f)
4-OH-3-NO2-C6H3 (1d)
2-Thienyl (1g)
4-CH3OC6H4 (1c)
4-BrC6H4 (1h)
3,4-OCH2OC6H3 (1i)
4-BrC6H4 (1h)
3,4,5-(CH3O)3C6H2 (1j)
4-(Benzo[d]oxazol-2yl)C6H4 (1k)
4-OH-3-CH3OC6H3 (1l)
4-CH3C6H4 (1m)
4-BrC6H4 (1h)
3,4-(CH3O)2C6H3 (1n)
2-Thienyl (1g)
C6H5CH2 (1o)
3c
3c
4j
4k
4l
3d
3d
3d
3d
3d
3e1
3e1
3e2
3e2
3f1
3f1
3f2
3f1
H
H
H
4m
4n
4o
4p
4q
4r
4s
4t
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
C6H5
C6H5
C6H5
H
CH3
CH3
H
4-CH3OC6H4 (1c)
4-ClC6H4 (1a)
2-Thienyl (1g)
4x
4y
4z
C6H5
CH3
a Isolated yields.
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Table 4 The synthesis of some of compounds 4 in water at 150 ◦C using
conventional heating
Entry
Product
Time/h
Yield (%)
1
2
3
4
5
6
7
8
9
4a
4b
4c
4e
4f
2
2
2
2
2
2
2
2
2
84
87
81
79
85
86
75
82
78
4j
4k
4q
4y
displayed high reactivity and a clean reaction under these standard
conditions. It is important to note that this protocol could be
applied not only to alicyclic amines (Table 3, entries 1–4), but
also to aminoacetic acid (Table 3, entries 5–7), aliphatic amines
(Table 3, entries 8–15) and aromatic amines (Table 3, entries
16–23).
Additionally, we performed the reactions for synthesizing some
of compounds 4 under classical heating conditions using p-TsOH
as a catalyst in high-temperature water. A comparison of the
results for the nine compounds listed in Table 3 and Table 4
indicated that the reaction was efficiently promoted by microwave
irradiation, and the reaction times were strikingly shortened to 2–
6 min from the 2 h required under traditional heating conditions,
and the yields were increased obviously too.
Fig. 1 The molecular structure of 4b.
4z (Fig. 2), the distance between the proton at C14 and the benzene
˚
ring (C17 to C22) was 2.53 A, indicating that it was strongly shielded
by the benzene ring (C17 to C22).17
The structures of all the synthesized compounds were based
on their spectroscopic data. The structures of 4b and 4z were
established by X-ray crystallographic analysis (Figs. 1 and 2,
respectively).19 The IR spectrum of compound 4b showed strong
The formation of 4 is likely to proceed via initial condensation
of aldehydes 1 with 1,3-indanedione 2 to afford 2-arylideneindene-
1,3-dione 5, which further undergoes in situ Michael addition
reaction with enaminones 3 to yield products 4 (Scheme 3). In
order to support the proposed mechanism, the compound 5h was
prepared independently from p-bromobenzaldehyde 1h and 1,3-
indanedione 2 and then employed in a two component reaction
with enaminone 3d to afford product 4l in 92% yield. However,
p-bromobenzaldehyde 1h first condensed with 3d followed by
reaction with 1,3-indanedione 2 failed to give the target compound
4. Instead, compound 6 and intermediate 5h were obtained
respectively (Scheme 4). When p-bromobenzaldehyde 1h was first
absorptions at 1684 cm−1 and 1645 cm−1 due to the C O group.
=
1
The H NMR spectrum of 4b showed a triplet at d 3.58 due to
the NCH proton and a singlet at d 4.76 due to the CH proton.
It is particularly noteworthy that when R1 was an aryl group, a
doublet appeared in the 4.91–5.27 ppm region (see 1H NMR data),
which belonged to the aromatic protons in compounds 4p–z. This
unusually upfield absorption could be explained according to the
X-ray diffraction analysis result of 4z. In the crystal structure of
Fig. 2 The molecular structure of 4z.
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in DMSO-d6 with chemical shift (d) given in ppm relative to
TMS as internal standard. Elemental analyses were determined by
using a Perkin-Elmer 240c elemental analysis instrument. X-Ray
crystallographic analysis was performed with a Siemens SMART
CCD and a Semens P4 diffractometer.
General procedure for the syntheses of compounds 4 with
microwave irradiation
All the reactions were performed in a monomodal EmrysTM
Creator from Personal Chemistry, Uppsala, Sweden. In a 10 mL
EmrysTM reaction vial, an aldehyde 1 (1 mmol), 1,3-indanedione 2
(1 mmol), an enaminone 3 (1 mmol), p-TsOH (1 mmol) and water
(1.0 mL) were mixed and then capped. The mixture was irradiated
Scheme 3 The possible reaction mechanism.
condensed with 3e1 followed by reaction with 1,3-indanedione 2,
the desired compound 4q was not obtained. Instead, compound 7
and unreacted 2 were isolated respectively (Scheme 5).
◦
for a given time at power of 250 W at 150 C. Upon completion
as monitored by TLC, the reaction mixture was cooled to room
temperature. The resulting suspension was neutralized with 0.4 mL
of 10% NaOH. Then the mixture was stirred for 5 min and the solid
was collected by Bu¨chner filtration and washed with EtOH (95%),
and subsequently dried and recrystallized from EtOH (95%) to
give the pure red product.
Conclusion
In conclusion, we have developed a microwave-assisted, three-
component condensation of aldehydes, 1,3-indanedione and
enaminones using p-toluene sulfonic acid (p-TsOH) as a catalyst
in high-temperature water, and have shown its application to the
synthesis of a number of poly-substituted indeno[1,2-b]quinolines.
This green procedure offers several advantages including opera-
tional simplicity, clean reactions, increased safety for small-scale
high-speed synthesis, and minimal environmental impact that
make it a useful and attractive process for the synthesis of these
compounds.
General procedure for the synthesis of compounds 4 with
conventional heating
A mixture containing an aldehyde 1 (1 mmol), 1,3-indanedione
2 (1 mmol), an enaminone 3 (1 mmol), p-TsOH (1 mmol) and
water (1.0 mL) was introduced into a 10 mL EmrysTM reaction
vial, capped and then stirred at 150 ◦C (oil bath temperature) for
two hours. The subsequent work-up procedure was the same as in
the microwave irradiation reactions.
Experimental
General
5-Cyclopropyl-7,8-dihydro-7,7-dimethyl-10-(4-nitrophenyl)-5H-
indeno[1,2-b]quinoline-9,11(6H,10H)-dione (4b)
Microwave irradiation was carried out with a microwave oven
(EmrysTM Creator from Personal Chemistry, Uppsala, Sweden).
Melting points were determined in open capillaries and were
uncorrected. IR spectra were taken on a FT-IR-Tensor 27
spectrometer in KBr pellets and reported in cm−1. 1H NMR
spectra were measured on a Bruker DPX 400 MHz spectrometer
IR (KBr, m, cm−1): 2959, 2869, 1677, 1647, 1556, 1518, 1346, 1219,
1136, 878, 727; 1H NMR (DMSO-d6) (d, ppm): 8.10 (d, 2H, ArH,
J = 8.4 Hz), 7.83 (d, 1H, ArH, J = 7.6 Hz), 7.48–7.46 (m, 2H,
ArH), 7.36 (d, 2H, ArH, J = 8.4 Hz), 7.32 (d, 1H, ArH, J =
7.6 Hz), 4.62 (s, 1H, CH), 3.60 (t, 1H, CH, J = 3.2 Hz), 3.12 (d,
Scheme 4 The investigation of a possible reaction mechanism.
Scheme 5 The investigation of a possible reaction mechanism.
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1H, CH2, J = 17.2 Hz), 2.75 (d, 1H, CH2, J = 17.2 Hz), 2.27 (d,
1H, CH2, J = 16.0 Hz), 2.20 (d, 1H, CH2, J = 16.0 Hz), 1.32–1.26
(m, 2H, CH2), 1.05 (s, 6H, CH3), 1.02–0.86 (m, 2H, CH2), Anal
calcd. for C27H24N2O4, C, 73.62; H, 5.49; N, 6.36; found C, 73.81;
H, 5.43; N, 6.51%.
2 (2 mmol) and water (1.0 mL) were mixed and then capped. The
mixture was irradiated for 2 min at 250 W power and 150 ◦C. Upon
completion, the reaction mixture was cooled to room temperature
and then filtered, washed with EtOH (95%), and subsequently
dried and recrystallized from EtOH (95%) to give the pure product
5h.
2-(10-(4-Fluorophenyl)-6,7,8,9-tetrahydro-7,7-dimethyl-9,11-
dioxo-10H-indeno[1,2-b]quinolin-5(11H)-yl)acetic acid (4f)
Substep reaction of aldehyde 1h, enaminone 3d or 3e1 and
1,3-indanedione 2
IR (KBr, m, cm−1): 2965, 1731, 1682, 1627, 1602, 1549, 1403, 1379,
1
The reaction was performed in a monomodal EmrysTM Cre-
ator from Personal Chemistry, Uppsala, Sweden. In a 10 mL
EmrysTM reaction vial, 4-bromobenzaldehyde 1h (1 mmol), 3-
amino-5,5-dimethylcyclohex-2-enone 3d (or 5,5-dimethyl-3-(4-
methylphenylamino)cyclohex-2-enone 3e1) (1 mmol), p-TsOH
(1 mmol) and water (1.0 mL) were mixed and then capped. The
mixture was irradiated for 2 min at a power of 250 W and 150 ◦C,
and then 1,3-indanedione 2 (1 mmol) was added. The mixture was
irradiated for 3 min at 250 W power and 150 ◦C again. Upon
completion (TLC monitoring), the reaction mixture was cooled to
room temperature. The resulting suspension was neutralized with
0.4 mL of 10% NaOH. Then the mixture was stirred for 5 min
and the solid was collected by Bu¨chner filtration and washed with
EtOH (95%). The solid was purified by column chromatography
on silica gel (200–300 mesh) using petroleum ether (bp 60–90 ◦C)–
acetone (1 : 1) as eluent to give compounds 5h, 6 and 7.
1221, 984, 874, 740; H NMR (DMSO-d6) (d, ppm): 13.71 (br s,
1H, COOH), 7.44–7.41 (m, 1H, ArH), 7.36–7.30 (m, 5H, ArH),
7.05–7.00 (m, 2H, ArH), 5.09–4.98 (m, 2H, CH2), 4.80 (s, 1H,
CH), 2.86–2.85 (m, 1H, CH2), 2.40–2.35 (m, 1H, CH2), 2.24 (d,
1H, CH2, J = 16.0 Hz), 2.14 (d, 1H, CH2, J = 16.0 Hz), 1.03
(s, 3H, CH3), 0.95 (s, 3H, CH3). Anal calcd. for C26H22FNO4, C,
72.38; H, 5.14; N, 3.25; found C, 72.51; H, 5.05; N, 3.32%.
10-(4-Bromophenyl)-7,8-dihydro-5,7,7-trimethyl-5H-indeno[1,2-
b]quinoline-9,11(6H,10H)-dione (4j)
IR (KBr, m, cm−1): 2953, 2868, 1677, 1643, 1626, 1549, 1368, 1215,
1008, 871, 692; 1H NMR (DMSO-d6) (d, ppm): 7.67 (d, 1H, ArH,
J = 7.6 Hz), 7.46–7.43 (m, 1H, ArH), 7.40 (d, 2H, ArH, J =
8.4 Hz), 7.37–7.30 (m, 2H, ArH), 7.17 (d, 2H, ArH, J = 8.4 Hz),
4.78 (s, 1H, CH), 3.74 (s, 3H, NCH3), 2.90 (d, 1H, CH2, J =
17.2 Hz), 2.55 (d, 1H, CH2, J = 17.2 Hz), 2.22–2.14 (m, 2H, CH2),
1.06 (s, 3H, CH3), 1.00 (s, 3H, CH3). Anal calcd. for C25H22BrNO2,
C, 66.97; H, 4.95; N, 3.12; found C, 67.11; H, 4.87; N, 3.20%.
2-(4-Bromobenzylidene)-2H-indene-1,3-dione (5h). Mp: 176–
◦
178 C; IR (KBr, m, cm−1): 3084, 3009, 2941, 1714, 1676, 1587,
1275, 804, 743; 1H NMR (DMSO-d6) (d, ppm): 8.45 (d, 2H, ArH,
J = 8.4 Hz), 8.04–8.02 (m, 2H, ArH), 7.99–7.97 (m, 2H, ArH),
7.85 (s, 1H, CH), 7.81 (d, 2H, ArH, J = 8.4 Hz); Anal calcd. for
C16H9BrO2, C, 61.37; H, 2.90; found C, 61.52; H, 2.81%.
7,8-Dihydro-10-(thiophen-2-yl)-5-p-tolyl-5H-indeno[1,2-
b]quinoline-9,11(6H,10H)-dione (4s)
IR (KBr, m, cm−1): 3059, 2943, 2923, 2866, 1678, 1643, 1588, 1510,
1
1395, 1177, 896, 844, 711; H NMR (DMSO-d6) (d, ppm): 7.59–
9-(4-Bromophenyl)-3,4,6,7-tetrahydro-3,3,6,6-tetramethylacri-
dine-1,8(2H,5H,9H,10H)-dione (6). Mp: >300 ◦C; IR (KBr,
m, cm−1): 3273, 2931, 1644, 1579, 1427, 833, 753; 1H NMR (DMSO-
d6) (d, ppm): 9.35 (s, 1H, NH), 7.36 (d, 2H, ArH, J = 8.4 Hz), 7.10
(d, 2H, ArH, J = 8.4 Hz), 4.77 (s, 1H, CH), 2.46 (d, 2H, CH2, J =
17.2 Hz), 2.32 (d, 2H, CH2, J = 17.2 Hz), 2.18 (d, 2H, CH2, J =
16.0 Hz), 1.99 (d, 2H, CH2, J = 16.0 Hz), 1.01 (s, 6H, 2CH3), 0.86
(s, 6H, 2CH3); Anal. calcd. for C23H26BrNO2, C, 64.49; H, 6.12;
N, 3.27; Found C, 64.43; H, 6.09; N, 3.33%.
7.58 (m, 1H, thiophenyl-H), 7.47 (d, 2H, ArH, J = 7.6 Hz), 7.42–
7.40 (m, 1H, thiophenyl-H), 7.32–7.21 (m, 3H, ArH), 7.07–7.03
(m, 1H, thiophenyl-H), 6.91–6.89 (m, 2H, ArH), 5.27 (d, 1H, ArH,
J = 7.6 Hz), 5.20 (s, 1H, CH), 2.48 (s, 3H, CH3), 2.33–2.31 (m,
3H, CH2), 2.16–2.11 (m, 1H, CH2), 1.92–1.69 (m, 2H, CH2); Anal
calcd. for C27H21NO2S, C, 76.57; H, 5.00; N, 3.31; S, 7.57; found
C, 76.40; H, 5.12; N, 3.41; S, 7.43%.
10-Benzyl-7,8-dihydro-7,7-dimethyl-5-phenyl-5H-indeno[1,2-
b]quinoline-9,11(6H,10H)-dione (4t)
9-(4-Bromophenyl)-3,4-dihydro◦-3,3,7-trimethylacridin-1(2H,
9H,10H)-one (7). Mp: 240–241 C; IR (KBr, m, cm−1): 3270,
IR (KBr, m, cm−1): 3026, 2960, 1686, 1637, 1587, 1398, 1101, 882,
718; 1H NMR (DMSO-d6) (d, ppm): 7.61–7.52 (m, 4H, ArH), 7.34
(d, 1H, ArH, J = 6.8 Hz), 7.26–7.18 (m, 4H, ArH), 6.94 (t, 1H,
ArH, J = 7.6 Hz), 6.89 (d, 2H, ArH, J = 6.8 Hz), 6.21 (s, 1H,
ArH), 4.91 (d, 1H, ArH, J = 7.6 Hz), 4.20 (t, 1H, CH, J = 3.8 Hz),
2.87–2.78 (m, 2H, CH2), 2.28 (s, 2H, CH2), 2.16 (d, 1H, CH2, J =
17.6 Hz), 1.63 (d, 1H, CH2, J = 17.6 Hz), 0.93 (s, 3H, CH3), 0.91
(s, 3H, CH3). Anal calcd. for C31H27NO2, C, 83.57; H, 6.11; N,
3.14; found C, 83.76; H, 6.02; N, 3.16%.
1
3089, 1696, 1618, 1552, 1486, 1288, 1145; H NMR (400 MHz,
DMSO-d6) (d, ppm): 9.42 (1H, s, NH), 7.37 (2H, d, ArH J =
8.4 Hz), 7.11 (2H, d, ArH, J = 8.4 Hz), 6.92–6.83 (3H, m, ArH),
5.02 (1H, s, CH), 2.48 (s, 3H, CH3), 2.44 (d, 1H, CH2, J = 17.2 Hz),
2.29 (d, 1H, CH2, J = 17.2 Hz), 2.16 (d, 1H, CH2, J = 16.0 Hz),
1.94 (d, 1H, CH2, J = 16.0 Hz), 1.03 (s, 3H, CH3), 0.93 (s, 3H,
CH3); Anal. calcd. for C21H20BrNO, C, 65.98; H, 5.27; N, 3.66;
found C, 66.06; H, 5.21; N, 3.77%.
Acknowledgements
Preparation of compound 5h
The reaction was performed in a monomodal EmrysTM Creator
from Personal Chemistry, Uppsala, Sweden. In a 10 mL EmrysTM
reaction vial, 4-bromobenzaldehyde 1h (2 mmol), 1,3-indanedione
We are grateful for financial support from the National Science
Foundation of China (No. 20372057) and Natural Science Foun-
dation of the Jiangsu Province (No. BK 2006033).
3984 | Org. Biomol. Chem., 2006, 4, 3980–3985
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19 The single-crystal growth was carried out in DMF at room temperature.
Crystal data for 4b: C27H24N2O4, red, crystal dimensions 0.64 × 0.26 ×
˚
0.15 mm, monoclinic, space group C2/c, ◦a = 28.768(5) A, b =
◦
˚
˚
˚
8.9966(12) A, c = 17.703(5) A, a = c = 90 , b = 108.727(4) , V =
4339.2(12) A , Mr = 440.48, Z = 8, Dc = 1.349 Mg m−3, k(Mok a) =
3
0.71070 A, l = 0.091 mm−1, F(000) = 1856, 3.14 < h < 25.35◦, R =
◦
˚
0.0617, wR2 = 0.1182. S = 1.195, largest diff. peak and hole: 0.158
and −0.173 e A−3. 4z: C59H53N3O5S2, red, crystal dimensions 0.43 ×
˚
˚
0.32 × 0.28 mm, monoclinic, space group P21/c,◦a = 15.081(2) A,
◦
˚
˚
˚
b = 9.4381(14) A, c = 35.102(6) A, a = c = 90 , b = 92.041(3) ,
V = 4992.9(13) A , Mr = 948.16, Z = 4, Dc = 1.261 Mg m−3, k(Mok
3
a) = 0.71073 A, l = 0.160 mm−1, F(000) = 2000, 1.75 < h < 25.01◦,
◦
˚
R = 0.0629, wR2 = 0.1486. S = 1.017, largest diff. peak and hole:
0.408 and −0.374 e A−3. CCDC reference numbers 617295 and 617296.
˚
12 J. R. Brooks, C. Berman, M. Hichens, R. L. Primka, G. F. Reynolds
and G. H. Rasmusson, Proc. Soc. Exp. Biol. Med., 1982, 169, 67.
For crystallographic data in CIF or other electronic format see DOI:
10.1039/b611462h.
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