An efficient method for synthesis of pyrano[3,2-c]pyridine derivatives under microwave irradiation

Article abstract of DOI:10.1002/jhet.152

(Chemical Equation Presented) A series of pyrano[3,2-c]pyridine derivatives were synthesized via reactions of 3,5-dibenzylidenepiperidin-4-one and malononitrile in N,N-dimethylformamide under microwave irradiation. It is a simple, efficient, and promising

Full text of DOI:10.1002/jhet.152

828
An Efficient Method for Synthesis of Pyrano[3,2-c]pyridine
Derivatives under Microwave Irradiation
Vol 46
Shu-Liang Wang, Zheng-Guo Han, Shu-Jiang Tu,* Xiao-Hong Zhang,
Shu Yan, Wen-Juan Hao, Feng Shi, Xu-Dong Cao, and Shan-Shan Wu
School of Chemistry and Chemical Engineering, Xuzhou Normal University, Key Laboratory of
Biotechnology for Medicinal Plant, Xuzhou, Jiangsu 221116, People’s Republic of China
*E-mail: laotu2001@263.net
Received August 28, 2008
DOI 10.1002/jhet.152
Published online 19 August 2009 in Wiley InterScience (www.interscience.wiley.com).
A series of pyrano[3,2-c]pyridine derivatives were synthesized via reactions of 3,5-dibenzylidene-
piperidin-4-one and malononitrile in N,N-dimethylformamide under microwave irradiation. It is a sim-
ple, efficient, and promising synthetic method to construct pyrano[3,2-c]pyridine skeleton.
J. Heterocyclic Chem., 46, 828 (2009).
INTRODUCTION
RESULTS AND DISCUSSION
Since the cytotoxic activity of (E)-3,5-bis (benzyli-
dene)-4-piperidones 1 (Fig. 1) and their specificity
toward leukemia cell lines with IC50 values <10 lM
have been reported [1] in 1992, the design and synthesis
of their derivatives have been an object of big interest
because of their potential application. The practice of
incorporating chalcones into heterocyclic nitrogenous
ring has been noticed recently [2–6]. The studies show
that compound 2 is potential broad-spectrum antitumor
agents [4].
To explore conditions of the reaction of 3,5-dibenzyli-
denepiperidin-4-one 3 and malononitrile 4 in DMF
(Scheme 1) under MWI, various reaction conditions
were investigated, including solvent and temperature. To
search for the optimal reaction solvent, the reaction of
3,5-bis(4-chlorobenzylidene)-1-methylpiperidin-4-one (3c)
and malononitrile 4, was examined in ethylene glycol,
DMF, glacial acetic acid, and ethanol, respectively (Ta-
ble 1, entries 1–4) under MWI at the maximum power
of 200 W. As shown in Table 1, the reaction in DMF
resulted in higher yields and shorter reaction time than
others. So DMF was chosen as the appropriate solvent.
To further optimize the reaction condition, the same
reaction was carried out in DMF at temperatures ranging
from 90 to 140ꢀC (Table 1, entries 5–9), with an incre-
ment of 10ꢀC each time. As shown in Table 1, the
yields of product was increased and the reaction time
was shortened when the temperature was increased from
90 to 120ꢀC, however, further increase of the tempera-
ture from 130 to 140ꢀC failed to improve the yield (Ta-
ble 1, entries 9 and 10). Therefore, 120ꢀC was chosen
as the most suitable temperature for all further micro-
wave-assisted reactions.
Microwave irradiation (MWI) of organic reactions has
rapidly gained popularity because it accelerates a variety
of synthetic transformations [7] and have the prominent
advantages of short reaction time and high yield [8].
It is well known that the 2-amino-3-cyanopyrans was
obtained by the reaction of chalcones with malononi-
trile, and several articles on this topic can be found in
the literature [9]. However, there are few reports for the
synthesis of 2. These methods generally required long
reaction time [4,5] or used EtONa [6] as catalyst. To
provide vast new compounds for biomedical screening,
a simple and efficient method for the synthesis of these
molecules is urgently required.
In continuation of our recent interest in the con-
struction of heterocyclic scaffolds [10], we herein
describe a practical, inexpensive, rapid microwave-
assisted method for the preparation of pyrano[3,2-c]
pyridine derivatives via reactions of 3,5-dibenzylidenepi-
peridin-4-one and malononitrile in N,N-dimethylforma-
mide (DMF) (Scheme 1).
Based on these optimized conditions [DMF, 120ꢀC,
200 W (maximum power)], reactions of different 3,5-
dibenzylidenepiperidin-4-ones and malononitrile were
performed, a series of pyrano[3,2-c]pyridine derivatives
were synthesized with good yields. The results (Table 2,
entries 1–12) indicated that for 3,5-dibenzylidenepiperi-
din-4-one bearing different functional groups such as
C
V
2009 HeteroCorporation

September 2009
An Efficient Method for Synthesis of Pyrano[3,2-c]pyridine Derivatives
under Microwave Irradiation
829
Table 1
Optimization for the synthesis of 5c.
Entry
Solvent
T (ꢀC)
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
9
HOAc
Glycol
DMF
EtOH
DMF
DMF
DMF
DMF
DMF
100
100
100
100
90
8
8
8
8
8
7
6
6
6
45
86
91
83
90
92
94
92
90
Figure 1. 3,5-Dibenzylidenepiperidin-4-one and its derivatives.
110
120
130
140
chloro, bromo, fluoro, nitro, or methyl the reaction pro-
ceeded smoothly in all cases. We have also observed
the electronic effects: that is, 3,5-dibenzylidenepiperi-
din-4-one with electron-withdrawing groups (Table 2,
entries 3–6) reacted rapidly, whereas electron-rich
groups (Table 2, entry 2) decreased the reactivity,
requiring longer reaction time.
IR spectra were recorded on an FTIR-tensor 27 spectrometer.
1H NMR spectra were measured on a DPX 400 MHz spec-
trometer using TMS as an internal standard and DMSO-d6 as
solvent. Elemental analysis was determined by using a Perki-
nElmer 240c elemental analysis instrument.
General procedure for the synthesis of compound 3N. In
a 50 mL reaction vial, a mixture of 4-piperidone (10 mmol),
the appropriate aldehyde (20 mmol), 1 mL 10% NaOH
and 30 mL 95% EtOH was stirred at room temperature for
0.5–2 h. The separated solid was then filtered.
General procedure for the synthesis of compound 5
under MWI. In a 10 mL reaction vial, the 3,5-dibenzylidene-
piperidin-4-one 3 (1 mmol), malononitrile (1.1 mmol), and
DMF (2 mL) were mixed and then capped. The mixture was
irradiated at 200 W (initial power 150 W, maximum power
200 W) at 120ꢀC for a given time. On completion (the reac-
tion was monitored by TLC), the reaction mixture was cooled
to room temperature and poured into water (70 mL), filtered to
give the crude product, which was further purified by recrystal-
lization from 95% EtOH to give pure product.
A possible mechanism for the formation of the prod-
uct 5 is outlined in Scheme 2. We proposed that the for-
mation of 5 proceeds via an initial Michael addition
reaction of chalcones and malononitrile to afford inter-
mediate 6, which then cyclized to give compound 5.
The structures of all the synthesized compounds were
established on the basis of their spectroscopic data. The
IR spectrum of compound 5b showed strong absorptions
at 3389 cmꢁ1 and 3295 cmꢁ1 due to the NH2 group,
1
2178 cmꢁ1 due to the CN group. The H NMR spec-
trum of 5b showed a broad singlet at d 6.76 due to the
ANH2 proton and a singlet at d 6.87 due to the ¼¼CH
proton. In the IR spectrum of compound 5h, the appear-
ance of bands at 3329 cmꢁ1, 3279 cmꢁ1, and 2192
ꢁ1
due to the NH2 and CN triple bound. The appearance of
a broad singlet at d 6.90 due to the NH2 protons and a
2-Amino-8-benzylidene-5,6,7,8-tetrahydro-6-methyl-4-phe-
nyl-4H-pyrano[3,2-c]pyridine-3-carbonitrile (5a). IR (KBr)
3338, 3284, 2189, 1683, 1640, 1619, 1594, 1489, 1453, 1415,
1399, 1326, 1272, 1218, 1171, 1110, 1050, 917, 904, 878,
1
singlet at d 6.92 due to ¼¼CH in the H NMR spectrum
further confirmed the structure of product.
In conclusion, we have developed a simple and effi-
cient method for the synthesis of pyrano[3,2-c]pyridine
derivatives. The protocol includes particularly valuable
features of excellent yield, shorten reaction time,
reduced environmental impact, and straightforward
procedure.
766, 756, 699 cmꢁ1 1H NMR (DMSO-d6): d 7.43–7.35 (m,
.
4H, ArH), 7.31–7.22 (m, 6H, ArH), 6.93 (s, 1H, ¼¼CH), 6.84
(brs, 2H, NH2), 4.06 (s, 1H, CH), 3.48 (d, 1H, J ¼ 14.4 Hz,
CH2), 3.28 (d, 1H, J ¼ 14.4 Hz, CH2), 3.00 (d, 1H, J ¼ 16.0
Hz, CH2), 2.57 (d, 1H, J ¼ 16.0 Hz, CH2), 2.15 (s, 3H, CH3).
13C NMR (DMSO-d6): d ¼ 159.79, 143.49, 139.15, 135.93,
128.96, 128.69, 128.49, 127.60, 127.46, 127.14, 121.43,
120.44, 113.23, 112.71, 55.86, 54.56, 54.08, 44.50, 41.07.
Anal. Calcd for C23H21N3O: C, 77.72; H, 5.96; N, 11.82;
found C, 77.83; H, 5.94; N, 11.79.
EXPERIMENTAL
8-(4-Methylbenzylidene)-2-amino-4-(4-methylphenyl)-5,6,7,8-
tetrahydro-6-methyl-4H-pyrano[3,2-c]pyridine-3-carbonitrile
(5b). IR (KBr) 3389, 3295, 2178, 1682, 1644, 1604, 1511,
1461, 1448, 1416, 1395, 1323, 1269, 1205, 1171, 1101, 1055,
All reactions were performed in a monomodal EmrysTM
Creator from Personal Chemistry, Uppsala, Sweden. Melting
points were determined in open capillaries and are uncorrected.
1
911, 812 cmꢁ1. H NMR (DMSO-d6): d 7.22 (d, 2H, J ¼ 8.0
Scheme 1
Hz ArH), 7.17–7.13 (m, 4H, ArH), 7.09 (d, 2H, J ¼ 8.0 Hz,
ArH), 6.87 (s, 1H, ¼¼CH), 6.76 (brs, 2H, NH2), 3.99 (s, 1H,
CH), 3.46 (d, 1H, J ¼ 14.8 Hz, CH2), 3.28 (d, 1H, J ¼ 17.2
Hz, CH2), 2.96 (d, 1H, J ¼ 16.4 Hz, CH2), 2.53 (d, 1H, J ¼
17.6 Hz, CH2), 2.31 (s, 3H, CH3), 2.29 (s, 3H, CH3), 2.14 (s,
3H, CH3). 13C NMR (DMSO-d6): d ¼ 159.72, 140.55, 139.08,
136.53, 136.21, 133.09, 129.23, 129.09, 128.92, 127.50,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

830
S.-L. Wang, Z.-G. Han, S.-J. Tu, X.-H. Zhang, S. Yan, W.-J. Hao, F. Shi,
X.-D. Cao, and S.-S. Wu
Vol 46
Table 2
Synthesis of compounds 5 under microwave irradiation.
Entry
Product
R
Ar
Time/min
Yield (%)
Mp/ꢀC
1
2
5a
5b
5c
5d
5e
5f
5g
5h
5i
Methyl
Methyl
Methyl
Methyl
Methyl
Methyl
Benzyl
Benzyl
Benzyl
Benzyl
Benzyl
Benzyl
C6H5
6
9
6
7
7
7
6
7
7
7
7
7
93
92
94
91
92
93
94
94
93
90
89
92
200–202
4-CH3C6H4
4-ClC6H4
3-NO2C6H4
4-NO2C6H4
4-BrC6H4
C6H5
215–217 (214–215)a
238–240
225–227
3
4
5
238–240
245–246
226–228
243–245
235–237
225–227
233–236
242–244
6
7
8
9
4-ClC6H4
4-FC6H4
10
11
12
5j
5k
5l
3-NO2C6H4
4-NO2C6H4
4-BrC6H4
a Literature melting point.
126.80, 121.28, 120.48, 112.93, 55.99, 54.56, 54.17, 44.52,
40.70, 20.79, 20.65. Anal. Calcd for C25H25N3O: C, 78.30, H,
6.57; N, 10.96; found C, 78.39; H, 6.56; N, 10.92.
139.46, 130.70, 130.09, 128.98, 124.10, 123.70, 120.07,
119.95, 114.32, 56.01, 54.75, 54.25, 53.81, 44.30, 40.69. Anal.
Calcd for C23H19N5O5: C, 62.02, H, 4.30; N, 15.72; found C,
61.92; H, 4.32; N, 15.77.
8-(4-Chlorobenzylidene)-2-amino-4-(4-chlorophenyl)-5,6,7,8-
tetrahydro-6-methyl-4H-pyrano[3,2-c]pyridine-3-carbonitrile
(5c). IR (KBr) 3365, 3289, 2180, 1681, 1645, 1605, 1489,
1461, 1449, 1413, 1393, 1321, 1267, 1207, 1169, 1092, 1056,
8-(4-Bromobenzylidene)-2-amino-4-(4-bromophenyl)-5,6,7,8-
tetrahydro-6-methyl-4H-pyrano[3,2-c]pyridine-3-carbonitrile (5f).
IR (KBr) 3364, 3283, 2181, 1681, 1644, 1590, 1486, 1459,
1409, 1391, 1321, 1267, 1169, 1104, 1074, 1010, 910, 895,
1
1014, 986, 911, 817, 737, 697 cmꢁ1. H NMR (DMSO-d6): d
7.48–7.43 (m, 4H, ArH), 7.26 (m, 4H, ArH), 6.92 (brs, 2H,
NH2), 6.89 (s, 1H, ¼¼CH), 4.12 (s, 1H, CH), 3.46 (d, 1H, J ¼
13.6 Hz, CH2), 3.28 (d, 1H, J ¼ 14.8 Hz, CH2), 3.00 (d, 1H, J
¼ 16.0 Hz, CH2), 2.55 (d, 1H, J ¼ 16.0 Hz, CH2), 2.16 (s,
3H, CH3). 13C NMR (DMSO-d6): d ¼ 159.79, 142.43, 139.23,
134.78, 131.76, 131.72, 130.71, 129.47, 128.70, 128.51,
128.13, 120.36, 120.19, 113.25, 55.54, 54.39, 53.92, 44.40,
40.39. Anal. Calcd for C23H19Cl2N3O: C, 65.10, H, 4.51; N,
9.90; found C, 65.01; H, 4.53; N, 9.94.
828, 814, 734 cmꢁ1 1H NMR (DMSO-d6): d 7.61–7.56 (m,
.
4H, ArH), 7.23–7.18 (m, 4H, ArH), 6.89 (brs, 2H, NH2), 6.87
(s, 1H, ¼¼CH), 4.11 (s, 1H, CH), 3.46 (d, 1H, J ¼ 14.0 Hz,
CH2), 3.26 (d, 1H, J ¼ 14.0 Hz, CH2), 3.00 (d, 1H, J ¼ 16.4
Hz, CH2), 2.53 (d, 1H, J ¼ 16.4 Hz, CH2), 2.16 (s, 3H, CH3).
13C NMR (DMSO-d6): d ¼ 159.72, 142.77, 139.18, 135.05,
131.55, 131.36, 130.93, 129.78, 128.11, 120.35, 120.30,
120.18, 120.11, 113.16, 55.39, 54.32, 53.85, 44.33, 40.40.
Anal. Calcd for C23H19Br2N3O: C, 53.83, H, 3.73; N, 8.19;
found C, 53.96; H, 3.70; N, 8.15.
8-(3-Nitrobenzylidene)-2-amino-5,6,7,8-tetrahydro-6-methyl-
4-(3-nitrophenyl)-4H-pyrano[3,2-c]pyridine-3-carbonitrile (5d).
IR (KBr) 3359, 3267, 2190, 1676, 1639, 1596, 1522, 1456,
1416, 1348, 1266, 1174, 1116, 1052, 984, 899, 818, 738, 714,
2-Amino-6-benzyl-8-benzylidene-5,6,7,8-tetrahydro-4-phenyl-
4H-pyrano[3,2-c]pyridine-3-carbonitrile (5g). IR (KBr) 3299,
3259, 2189, 1684, 1639, 1618, 1592, 1491, 1453, 1400, 1374,
1349, 1269, 1218, 1169, 1100, 1075, 1042, 919, 878, 746, 696
682 cmꢁ1 1H NMR (DMSO-d6): d 8.19–8.14 (m, 2H, ArH),
.
1
8.09 (s, 1H, ArH) 8.06 (s, 1H, ArH), 7.75–7.69 (m, 4H, ArH),
7.05 (brs, 3H, NH2, and ¼¼CH), 4.41 (s, 1H, CH), 3.53 (d, 1H,
J ¼ 14.0 Hz, CH2), 3.28 (d, 1H, J ¼ 14.8 Hz, CH2), 3.09 (d,
1H, J ¼ 16.4 Hz, CH2), 2.59 (d, 1H, J ¼ 16.0 Hz, CH2), 2.17
(s, 3H, CH3). 13C NMR (DMSO-d6): d ¼ 159.98, 148.06,
147.94, 145.66, 139.42, 137.45, 135.14, 134.46, 130.48,
130.09, 129.62, 123.37, 122.41, 122.04, 121.84, 119.98,
119.84, 113.67, 55.07, 54.14, 53.60, 44.25, 40.48. Anal. Calcd
for C23H19N5O5: C, 62.02, H, 4.30; N, 15.72; found C, 62.17;
H, 4.28; N, 15.66.
cmꢁ1. H NMR (DMSO-d6): d 7.37–7.32 (m, 4H, ArH), 7.29–
7.25 (m, 2H, ArH), 7.23–7.19 (m, 4H, ArH), 7.18–7.16 (m,
3H, ArH), 7.09–7.07 (m, 2H, ArH), 6.95 (s, 1H, ¼¼CH), 6.86
(brs, 2H, NH2), 4.01 (s, 1H, CH), 3.63 (d, 1H, J ¼ 14.4 Hz,
Scheme 2
8-(4-Nitrobenzylidene)-2-amino-5,6,7,8-tetrahydro-6-methyl-
4-(4-nitrophenyl)-4H-pyrano[3,2-c]pyridine-3-carbonitrile (5e).
IR (KBr) 3365, 3293, 2182, 1688, 1642, 1593, 1521, 1458,
1418, 1392, 1340, 1273, 1172, 1097, 1055, 907, 868, 809, 716
1
cmꢁ1. H NMR (DMSO-d6): d 8.26 (d, 4H, J ¼ 8.0 Hz, ArH),
7.54 (d, 4H, J ¼ 8.8 Hz, ArH) 7.06 (brs, 2H, NH2), 7.03 (s,
1H, ¼¼CH), 4.36 (s, 1H, CH), 3.53 (d, 1H, J ¼ 14.4 Hz, CH2),
3.48–3.43 (m, 1H, CH2), 3.08 (d, 1H, J ¼ 16.4 Hz, CH2), 2.56
(d, 1H, J ¼ 16.4 Hz, CH2), 2.17 (s, 3H, CH3). 13C NMR
(DMSO-d6): d ¼ 159.91, 150.84, 146.75, 145.93, 142.74,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2009
An Efficient Method for Synthesis of Pyrano[3,2-c]pyridine Derivatives
under Microwave Irradiation
831
CH2), 3.45 (m, 3H, CH2), 3.07 (d, 1H, J ¼ 16.0 Hz, CH2),
2.69 (d, 1H, J ¼ 16.0 Hz, CH2). 13C NMR (DMSO-d6): d ¼
159.79, 143.48, 139.47, 137.74, 135.89, 128.87, 128.64,
128.38, 128.00, 127.56, 127.10, 126.91, 121.83, 120.39,
112.87, 59.89, 56.05, 52.26, 51.69, 41.07. Anal. Calcd for
C29H25N3O: C, 80.72, H, 5.84; N, 9.74; found C, 80.86; H,
5.83; N, 9.70.
CH2), 2.66 (d, 1H, J ¼ 15.6 Hz, CH2). 13C NMR (DMSO-d6):
d ¼ 159.90, 150.89, 146.73, 145.92, 142.73, 139.70, 137.52,
130.34, 130.01, 128.97, 128.57, 127.98, 126.95, 124.03,
123.60, 113.88, 59.42, 54.85, 51.58, 40.59. Anal. Calcd for
C29H23N5O5: C, 66.79; H, 4.45; N, 13.43; found C, 66.64; H,
4.47; N, 13.48.
8-(4-Bromobenzylidene)-2-amino-6-benzyl-4-(4-bromophenyl)-
5,6,7,8-tetrahydro-4H-pyrano[3,2-c]pyridine-3-carbonitrile (5l).
IR (KBr) 3326, 3293, 2196, 1681, 1644, 1594, 1485, 1407,
1392, 1373, 1322, 1267, 1170, 1098, 1071, 1010, 917, 887,
8-(4-Chlorobenzylidene)-2-amino-6-benzyl-4-(4-chlorophenyl)-
5,6,7,8-tetrahydro-4H-pyrano[3,2-c]pyridine-3-carbonitrile (5h).
IR (KBr) 3329, 3279, 2192, 1683, 1649, 1598, 1489, 1411,
1395, 1375, 1325, 1265, 1214, 1169, 1091, 1049, 1013, 917,
815, 749, 696 cmꢁ1 1H NMR (DMSO-d6): d 751–7.48 (m,
.
884, 826, 753, 700 cmꢁ1
.
1H NMR (DMSO-d6): d 7.43–7.39
4H, ArH), 7.14–7.12 (m, 5H, ArH), 7.10 (m, 2H, ArH) 7.02–
7.00 (m, 2H, ArH), 6.86 (brs, 2H, NH2), 6.84 (s, 1H, ¼¼CH),
3.99 (s, 1H, CH), 3.56 (d, 1H, J ¼ 14.4 Hz, CH2), 3.40–3.36
(m, 3H ,CH2), 3.00 (d, 1H, J ¼ 16.0 Hz, CH2), 2.60 (d, 1H, J
¼ 16.0 Hz, CH2). 13C NMR (DMSO-d6): d ¼ 159.77, 142.87,
139.46, 137.69, 135.06, 131.59, 131.34, 130.92, 129.83,
128.60, 128.01, 120.32, 120.23, 112.84, 59.62, 55.48, 51.75,
51.67, 40.36. Anal. Calcd for C29H23Br2N3O: C, 59.10, H,
3.94; N, 7.13; found C, 58.95; H, 3.95; N, 7.16.
(m, 4H, ArH), 7.23–7.17 (m, 7H, ArH), 7.07–7.06 (m, 2H,
ArH), 6.92 (s, 1H, ¼¼CH), 6.90 (brs, 2H, NH2), 4.07 (s, 1H,
CH), 3.61 (d, 1H, J ¼ 14.8 Hz, CH2), 3.46–3.42 (m, 3H,
CH2), 3.06 (d, 1H, J ¼ 16.8 Hz, CH2), 2.66 (d, 1H, J ¼ 16.0
Hz, CH2). 13C NMR (DMSO-d6): d ¼ 159.78, 142.45, 139.46,
137.69,134.73, 131.70, 130.62, 129.45 128.66, 128.60, 128.42,
127.99, 127.74, 126.94, 120.79, 120.19, 112.86, 112.72, 59.65,
55.60, 51.81, 51.61, 40.30. Anal. Calcd for C29H23Cl2N3O: C,
69.60, H, 4.63; N, 8.40; found C, 69.75; H, 4.62; N, 8.37.
8-(4-Fluorobenzylidene)-2-amino-6-benzyl-4-(4-fluorophenyl)-
5,6,7,8-tetrahydro-4H-pyrano[3,2-c]pyridine-3-carbonitrile (5i).
IR (KBr) 3334, 3298, 2197, 1684, 1650, 1602, 1507, 1417,
1398, 1375, 1267, 1225, 1157, 1091, 916, 831, 780, 756, 697
Acknowledgments. This work was supported by National Sci-
ence Foundation of China (No. 20672090), Natural Science
Foundation of the Jiangsu Province (No. BK20060330), the Qing
Lan Project (No. 08QLT001), and Six Kinds of Professional Elite
Foundation of Jiangsu Province (No. 06-A-039).
1
cmꢁ1. H NMR (DMSO-d6): d 7.25–7.20 (m, 4H, ArH), 7.19–
7.14 (m, 7H, ArH), 7.08–7.06 (m, 2H, ArH), 6.92 (s, 1H,
¼¼CH), 6.83 (brs, 2H, NH2), 4.05 (s, 1H, CH), 3.59 (d, 1H, J
¼ 14.0 Hz, CH2), 3.45 (s, 2H, CH2), 3.40 (d, 1H, J ¼ 14.4
Hz, CH2), 3.05 (d, 1H, J ¼ 16.0 Hz, CH2), 2.65 (d, 1H, J ¼
16.0Hz, CH2). 13C NMR (DMSO-d6): d ¼ 162.28, 159.72,
139.63, 139.37, 137.69, 132.28, 130.93, 130.85, 129.49,
129.40, 128.62, 127.99, 126.94, 120.86, 120.32, 115.51,
115.43, 115.30, 115.21, 112.66, 59.75, 55.84, 51.98, 51.57.
Anal. Calcd for C29H23F2N3O: C, 74.50; H, 4.96; N, 8.99;
found C, 74.66; H, 4.93; N, 8.95.
REFERENCES AND NOTES
[1] Dimmock, J. R.; Arora, V. K.; Duffy, M. J.; Reid, R. S.;
Allen, T. M.; Kao, G. Y. Drug Des Discov 1992, 8, 291.
[2] El-Barbary, A. A.; Khodair, A. I.; Pederson, E. B.; Nielsen,
C. J Med Chem 1994, 37, 73.
[3] Al-Obaid, A. M.; El-Subbagh, H. I.; Khodair, A. I.; El-
mazar, M. M. M. A. Anticancer Drugs 1996, 7, 873.
[4] El-Subbagh, H. I.; Abu-Zaid, S. M.; Mahran, M. A.; Badria,
F. A.; Al-Obaid, A. M. J Med Chem 2000, 43, 2915.
8-(3-Nitrobenzylidene)-2-amino-6-benzyl-5,6,7,8-tetrahydro-
4-(3-nitrophenyl)-4H-pyrano[3,2-c]pyridine-3-carbonitrile (5j).
IR (KBr) 3337, 3293, 2184, 1679, 1647, 1596, 1522, 1465,
1399, 1351, 1263, 1218, 1159, 1085, 914, 815, 739, 695, 685
[5] Hammam, A. E.-F. G.; Sharaf, M. A.; El-Hafez, N. A. A.
Indian J Chem Sect B 2001, 40B, 213.
[6] Kumar, R. R.; Perumal, S.; Senthilkumar, P.; Yogeeswari,
P.; Sriram, D. Bioorg Med Chem Lett 2007, 17, 6459.
1
cmꢁ1. H NMR (DMSO-d6): d 8.16–8.17 (m, 1H, ArH), 8.12–
[7] (a) Bose, A. K.; Banik, B. K.; Lavlinskaia, N.; Jayaraman,
M.; Manhas, M. S. Chemtech 1997, 27, 18; (b) Caddick, S. Tetrahe-
dron 1995, 51, 10403.
8.10 (m, 1H, ArH), 8.03 (brs, 2H, NH2), 7.70–7.65 (m, 4H,
ArH), 7.12–7.11 (m, 3H, ArH), 7.07 (s, 1H, ¼¼CH), 7.06–7.04
(m, 4H, ArH), 4.35 (s, 1H, CH), 3.66 (d, 1H, J ¼ 14.4 Hz,
CH2), 3.54 (d, 1H, J ¼ 15.2 Hz, CH2), 3.49–3.34 (m, 2H,
CH2), 3.13 (d, 1H, J ¼ 16.4 Hz, CH2), 2.69 (d, 1H, J ¼ 16.0
Hz, CH2). 13C NMR (DMSO-d6): d ¼ 159.78, 142.45, 139.46,
137.69, 134.73, 131.70, 130.62, 129.45, 128.66, 128.60,
128.42, 127.99, 127.74, 126.93, 120.79, 112.87, 59.65, 56.01,
55.60, 51.89, 51.81, 51.62, 40.29. Anal. Calcd for
C29H23N5O5: C, 66.79; H, 4.45; N, 13.43; found C, 66.96; H,
4.42; N, 13.39.
[8] Gedye, R.; Smith, F.; Westawaym, K.; Humera, A.; Baldi-
sern, L.; Laberge, L.; Rousell, J. Tetrahedron Lett 1986, 27, 279.
[9] (a) Soto, J. L.; Seoane, C.; Martin, N.; Blanco, L. A. Het-
erocycle 1983, 20, 803; (b) Soto, J. L.; Seoane, C.; Martin, N.; Quin-
teiro, M. Heterocycles 1984, 22, 1; (c) Popat, K. H.; Kachhadia, V.
V.; Nimavat, K. S.; Joshi, H. S. J Indian Chem Soc 2004, 81, 157; (d)
Armesto, D.; Horspool, W. M.; Martin, N.; Ramos, A.; Seoane, C. J
Chem Soc: Chem Commun 1987, 16, 1231; (e) Armesto, D.; Hors-
pool, W. M.; Martin, N.; Ramos, A.; Seoane, C. J Org Chem 1989,
54, 3069; (f) Gonzalez, R.; Martin, N.; Seoane, C.; Marco, J. L.;
Albert, A.; Cano, F. H. Tetrahedron Lett 1992, 33, 3809; (g) Martin,
N.; Seoane, C.; Soto, J. L. Tetrahedron 1988, 44, 5861; (h) Ciller, J.
A.; Martin, N.; Seoane, C.; Jose, L. S. J Chem Soc Perkin Trans 1
1985, 2581; (i) Bellanato, J.; Florencio, F.; Martin, N.; Seoane, C. J
Mol Struct 1988, 172, 63; (j) Bellanato, J.; Florencio, F.; Garcia
Blanco, S.; Martin, N.; Seoane, C. J Mol Struct 1987, 162, 19.
[10] Tu, S. J.; Jiang, B.; Zhang, Y.; Jia, R. H., Zhang, J. Y.;
Yao, C. S.; Shi, F. Org Biomol Chem 2007, 5, 355.
8-(4-Nitrobenzylidene)-2-amino-6-benzyl-5,6,7,8-tetrahydro-
4-(4-nitrophenyl)-4H-pyrano[3,2-c]pyridine-3-carbonitrile (5k).
IR (KBr) 3329, 3301, 2200, 1681, 1650, 1591, 1517, 1421,
1398, 1340, 1269, 1218, 1168, 1108, 920, 895, 859, 811, 748,
700 cmꢁ1 1H NMR (DMSO-d6): d 8.24–8.19 (m, 4H, ArH),
.
7.51–7.48 (m, 4H, ArH), 7.15 (s, 1H, ¼¼CH), 7.14–7.13 (m,
2H, ArH), 7.08–7.06 (m, 3H, ArH), 7.05 (brs 2H, NH2), 4.31
(s, 1H, CH), 3.69 (d, 1H, J ¼ 14.8 Hz, CH2), 3.53 (d, 1H, J ¼
14.8 Hz, CH2), 3.48 (s, 2H, CH2), 3.13 (d, 1H, J ¼ 16.4 Hz,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet