An efficient microwave-assisted synthesis furo[3,4-b]-[4,7]phenanthroline and indeno[2,1-b][4,7]phenanthroline derivatives in water

Article abstract of DOI:10.1002/jhet.5570450418

(Chemical Equation Presented) A series of furo[3,4-b][4,7]phenanthroline and indeno[2,1-b][4,7]phenanthroline derivatives were synthesized via a three-component reaction of aromatic aldehydes, 6-aminoquinoline and either tetronic acid or 1,3-indanedione in water, under microwave irradiation without use of any catalyst. This green procedure offers several advantages including operational simplicity, clean reaction, and increased safety for small-scale high-speed synthesis.

Full text of DOI:10.1002/jhet.5570450418

Jul-Aug 2008
1065
An Efficient Microwave-assisted Synthesis Furo[3,4-b]-
[4,7]phenanthroline and Indeno[2,1-b][4,7]phenanthroline
Derivatives in Water
Feng Shi, Dianxiang Zhou, Shujiang Tu*, Qingqing Shao, Chunmei Li, Longji Cao
School of Chemistry and Chemical Engineering, Xuzhou Normal University, Key Laboratory of Biotechnology
for Medicinal Plant, Xuzhou, Jiangsu, 221116, P. R. China
Received July 12, 2007
O
O
R
R
O
O
R
N
O
N
N
O
O
+
O
O
NH2
water
MWI
water
MWI
N
H
N
H
A series of furo[3,4-b][4,7]phenanthroline and indeno[2,1-b][4,7]phenanthroline derivatives were
synthesized via a three-component reaction of aromatic aldehydes, 6-aminoquinoline and either tetronic
acid or 1,3-indanedione in water, under microwave irradiation without use of any catalyst. This green
procedure offers several advantages including operational simplicity, clean reaction, and increased safety
for small-scale high-speed synthesis.
J. Heterocyclic Chem., 45, 1065 (2008).
INTRODUCTION
Compounds with the 4,7-phenanthroline motif, analogs
of ergot alkaloids, possess high and versatile
pharmacological effects, such as serotonin antagonism,
vasoconstriction, oxytocic and psychotropic activities
[15]. And they are also used as inhibitors of the pituitary
hormone prolactin [16] and fungicides [17].
Furopyridines [18] and 4,7-phenanthroline [19] have
been reported widely in the literature, but the synthesis of
the compounds incorporating both 4,7-phenanthroline and
furopyridine motifs have been neglected. Here we wish to
report a facile, rapid and green methodology for the
synthesis of furo[3,4-b][4,7]phenanthroline by three-
component condensations in water under microwave
irradiation (Scheme 1).
The similar polarity of classic organic solvents and
high-temperature water has aroused much interest in the
investigation of organic transformations in aqueous media
[1]. In addition to being a safe, readily available and
environmentally friendly solvent [2], water has also been
recognized as an effective reaction medium with unique
properties and possibilities for many organic reactions [3].
Simultaneously, high density microwave irradiation
(MWI) 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 and an aqueous medium offers a
nearly synergistic strategy in the sense that the
combination in itself offers greater potential than the two
parts in isolation [5]. 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 heating [6], must be
considered to be both promising and enabling green
alternatives.
Scheme 1
R
O
N
O
N
water
MWI
O
O
+
NH2
RCHO
+
O
N
H
1
2
3
4
Furopyridine is one of the most important “privileged
medicinal scaffolds,” which are molecular frameworks
used for the development of pharmaceutical agents for
diverse applications. Compounds incorporating this motif
show a wide range of pharmacological activities such as
antipsychotic [7], antianaphylactic [8], antiproliferative
[9], anticonvulsant [10], and anthelmintic activities [11],
and can also be used as calcium influx promoters [12],
HIV-1 nonnucleosidereverse transcriptase inhibitors [13],
and acetylcholinesterase inhibitors [14].
RESULTS AND DISCUSSION
To explore the scope and versatility of this method,
various reaction conditions were investigated, including
solvent and temperature variations. Highlighted in Table 1
for compound 4a, for example, is the influence of solvent
and temperature on the reaction yield. The MW-assisted
reaction of 4-fluorobenzaldehyde (1a, 1.0 mmol), 6-
aminoquinoline (2, 1.0 mmol) and tetronic acid (3, 1.0
mmol) was examined using glycol, glacial acetic acid,

1066
F. Shi, D. Zhou, S. Tu, Q. Shao, C. Li, L. Cao
Vol 45
ethanol water and N,N-dimethylformamide as solvent (2.0
mL) at 100 °C, respectively. All the reactions were carried
out at the maximum power of 250 W. The results are
summarized in Table 1.
It was shown in Table 1 that the reaction using glycol
or water as the solvent resulted in higher yields and
shorter reaction time than those using AcOH, DMF or
EtOH as solvents (Table 1, entries 1ꢀ5). Considering
environmental friendliness and the avoidance of using
toxic organic reagents, water was chosen as the solvent
for all further microwave-assisted reactions.
To further optimize reaction conditions, the same
reaction was carried out in water at temperatures ranging
from 90 to 140 °C, with an increment of 10 °C each time.
The yield of product 4a was increased and the reaction
time was shortened as the temperature was increased from
90 °C to 120 °C (Table 1, entries 6-8). However, further
increase of the temperature to 130-140 °C failed to
improve the yield of product 4a (Table 1, entries 9-10).
Therefore, 120 °C was chosen as the reaction temperature
for all further microwave-assisted reactions.
reactivity and clean reaction under these standard
conditions.
In order to expand the scope of the method, the
replacement of tetronic acid 3 with 1,3-indanedione 5 was
also examined. This is particularly attractive because
compounds containing the indenopyridine motif show a wide
range of biological activities, such as calcium antagonistic
[20], antioxidant [21], antihistamine, and antidepressant [22]
properties, and also act as phosphodiesterase (PDE)
inhibitors [23] and as NK-1 and dopamine receptor ligands
[24]. To our delight, the reactions proceeded smoothly under
the above optimized conditions and a series of indeno[2,1-
b][4,7]phenan-throline derivatives (Scheme 2) was obtained
in excellent yields. The results are summarized in Table 2.
Scheme 2
R
O
O
O
N
N
water
MWI
RCHO
+
+
NH2
N
H
2
1
5
6
Table 1
Table 2
Optimization of reaction conditions of compound 4a
The synthesis of some of compounds 4 and 6 under both MW and CH
conditions (120 °C)
Entry
Solvent
T / °C
Time / min
Yield / %
Entry
4 or 6
MW
Time / min
CH
Yield / %
1
2
3
Glycol
HOAc
EtOH
water
DMF
water
water
water
water
water
100
100
100
100
100
90
10
12
14
10
13
12
9
88
82
79
87
75
84
89
94
92
90
Yield / %
Time / h
1
2
3
4
5
6
7
8
4a
4e
4f
4l
6
7
8
8
7
9
8
8
94
92
90
94
93
91
92
92
4
3
3
4
4
4
3
4
75
54
49
51
70
41
61
47
4
5
6
7
110
120
130
140
6b
6f
6h
6l
8
9
10
6
7
7
The maximum power of microwave irradiation was
optimized by carrying out the same reaction at powers of
100, 150, 200, 250 and 300 W respectively, using water
as solvent at 120 °C. When the power was at 100ꢀ200 W,
the time taken for the temperature to reach 120 °C was too
long. Microwave irradiation at 250 W gave the highest
yield and the maximum temperature reached during the
reaction was 122 °C. Therefore, microwave power of 250
W was chosen as the optimum power.
The use of these optimal microwave experimental
conditions [water, 120 °C] for the reactions of different
aromatic aldehydes afforded good yields of furo[3,4-b]-
[4,7]phenanthroline derivatives. The results (Table 3,
entries 1-11) show that aromatic aldehydes bearing either
electron-donating (such as alkoxyl groups) or electron-
withdrawing (such as nitro or halide groups) functional
groups were all suitable for the synthesis of compounds 4.
Additionally, to demonstrate the purely nonthermal
microwave effects, the same temperature was applied to
synthesize some of products 4 and 6 under classical
heating (CH) conditions. The results listed in Table 2
showed the specific activation of this reaction under
microwave heating. Simultaneously, the reaction times
was strikingly shortened to minutes from hours required
in traditional heating condition, and the yields were
increased obviously too. The reason may be attributed to
the consequence of both thermal effects and specific
effects induced by the microwave field [25]. The reactants
in these MCRs contain dipoles and proceed via relatively
polar intermediates, which enhance their interactions with
MW and consequently benefit significantly from MW
irradiation in regard to more efficient reaction time, yield
and product purity.
Although the detailed mechanism of the above reaction
remains to be fully clarified, the formation of furo[3,4-b]-
[4,7]phenanthroline 4 could be explained by a possible
Moreover,
a
heterocyclic aldehyde, thiophene-2-
carbaldehyde (Table 3, entry 12), still showed high

Jul-Aug 2008 Furo[3,4-b]-[4,7]phenanthroline and Indeno[2,1-b][4,7]phenanthroline Derivatives in Water
1067
reaction sequence presented in Scheme 3. The product 4
may be synthesized via sequential condensation, addition,
cyclization and elimination. The condensation between
aldehyde 1 and tetronic acid 3 leads to intermediate 7,
Michael addition between 7 and 2 would give 8, which
upon intermolecular cyclization and dehydration to
generate the product 4.
number of furo[3,4-b][4,7]phenanthroline and indeno-
[2,1-b][4,7]phenanthroline derivatives. This green
procedure offers several advantages including operational
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.
Scheme 3
N
R
O
O
O
O
N
-H2O
O
NH2
RCHO
+
CHR
O
O
O
2
NH
O
1
8
3
7
R
R
R
O
O
O
O
N
N
N
-H2O
O
O
N
H
N
H
O
HO
NH2
4
10
9
Table 3
Synthesis of 4 and 6 under microwave irradiation at 120 °C
Entry
Product
4a
4b
4c
4d
4e
4f
R
Time / min
Yield / %
1
2
3
4-FC6H4
6
7
6
8
7
8
6
7
5
6
7
8
8
7
8
9
7
9
6
8
7
7
8
8
94
4-ClC6H4
93
4-BrC6H4
95
4
5
6
7
4-CH3OC6H4
2,4-Cl2C6H3
3,4-(CH3O)2C6H3
3-NO2C6H4
3,4-OCH2OC6H3
4-CH3C6H4
C6H5
92
92
90
4g
4h
4i
94
8
93
9
96
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
4j
93
4k
4l
4-OH-3-NO2C6H3
thiophen-2-yl
4-FC6H4
96
94
6a
6b
6c
6d
6e
6f
92
4-ClC6H4
93
93(61)[19(b)]
4-BrC6H4
4-CH3OC6H4
2,4-Cl2C6H3
3,4-(CH3O)2C6H3
3-NO2C6H4
3,4-OCH2OC6H3
4-CH3C6H4
C6H5
92
94
91
94(72)[19(b)]
6g
6h
6i
92
94
94
91
92
6j
4-OH-3-NO2C6H3
thiophen-2-yl
6k
6l
EXPERIMENTAL
In summary, we have developed a three-component
reaction of an aldehyde, 6-aminoquinoline and either
tetronic acid or 1,3-indanedione in high-temperature
water, and have shown its application to the synthesis of a
Microwave irradiation was carried out with a microwave oven
EmrysTM Creator from Personal Chemistry, Uppsala, Sweden.
Melting points were determined in the open capillaries and were

1068
F. Shi, D. Zhou, S. Tu, Q. Shao, C. Li, L. Cao
Vol 45
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
using TMS as an internal standard and DMSO-d6 as solvent.
Elemental analysis was determined by using a Perkin-Elmer
240c elemental analysis instrument.
11-(4-Methoxyphenyl)-8,11-dihydrofuro[3,4-b][4,7]phen-
anthrolin-10(7H)-one (4d). This compound was obtained
according to above general procedure, mp>300 °C; ir (potassium
bromide): 3249, 3114, 2996, 2868, 2833, 1722, 1650, 1580,
1
1468, 1398, 1302, 1210, 1110, 962, 846, 673 cm-1; H nmr: ꢀ
10.41 (s, 1H, NH), 8.68ꢁ8.67 (m, 1H, ArH), 8.23 (d, 1H, J = 8.4
Hz, ArH), 7.94 (d, 1H, J = 9.2 Hz, ArH), 7.52 (d, 1H, J = 9.2 Hz,
ArH), 7.38ꢁ7.35 (m, 1H, ArH), 7.12 (d, 2H, J = 8.8 Hz, ArH),
6.76 (d, 2H, J = 8.8 Hz, ArH), 5.67 (s, 1H, CH), 5.00ꢁ4.89 (m,
2H, CH2), 3.65 (s, 3H, OCH3). Anal. Calcd for C21H16N2O3: C,
73.24; H, 4.68; N, 8.13. Found C, 73.35; H, 4.61; N, 8.10.
11-(2,4-Dichlorophenyl)-8,11-dihydrofuro[3,4-b][4,7]-
phenanthrolin-10(7H)-one (4e). This compound was obtained
according to above general procedure, mp>300 °C; ir (potassium
bromide): 3238, 3127, 3063, 2932, 1723, 1653, 1580, 1467,
1396, 1353, 1255, 1097, 862, 762, 620 cm-1; 1H nmr: ꢀ 10.58 (s,
1H, NH), 8.69ꢁ8.68 (m, 1H, ArH), 8.00ꢁ7.94 (m, 2H, ArH),
7.55ꢁ7.49 (m, 2H, ArH), 7.43ꢁ7.40 (m, 1H, ArH),7.26 (d, 1H, J
= 8.0 Hz, ArH), 7.12 (s, 1H, ArH), 6.01 (s, 1H, CH), 5.02ꢁ4.93
(m, 2H, CH2). Anal. Calcd for C20H12Cl2N2O2: C, 62.68; H, 3.16;
N, 7.31. Found C, 62.60; H, 3.11; N, 7.24.
General procedure for the one-pot synthesis of furo[3,4-
in water under
b][4,7]phenanthroline derivatives
4
microwave irradiation conditions. Typically, in a 10-mL
EmrysTM reaction vial, aldehyde 1 (1 mmol), 6-aminoquinoline 2
(1 mmol), tetronic acid 3 (1 mmol) and water (2 mL) were
mixed and then capped. The mixture was irradiated for a given
time at 120 °C under microwave irradiation (initial power 200
W and maximum power 250 W). Upon completion, monitored
by TLC, the reaction mixture was filtered to give the crude
product, which was further purified by recrystallization from
EtOH (95%) to give pure furo[3,4-b][4,7]phenanthroline
derivatives 4.
General procedure for the one-pot synthesis of indeno[2,1-
b][4,7]phenanthroline derivatives
6
in water under
microwave irradiation conditions. Typically, in a 10-mL
EmrysTM reaction vial, aldehyde 1 (1 mmol), 6-aminoquinoline 2
(1 mmol), 1,3-indanedione 5 (1 mmol) and water (2 mL) were
mixed and then capped. The mixture was irradiated for a given
time at 120 °C under microwave irradiation (initial power 200
W and maximum power 250 W). Upon completion, monitored
by TLC, the reaction mixture was filtered to give the crude
product, which was further purified by recrystallization from
EtOH (95%) to give pure indeno[2,1-b][4,7]phenanthroline
derivatives 6.
11-(3,4-Dimethoxyphenyl)-8,11-dihydrofuro[3,4-b][4,7]-
phenanthrolin-10(7H)-one (4f). This compound was obtained
according to above general procedure, mp>300 °C; ir (potassium
bromide): 3246, 3177, 2996, 2932, 2835, 1726, 1656, 1594,
1
1466, 1350, 1293, 1164, 1013, 961, 830, 684 cm-1; H nmr: ꢀ
10.40 (s, 1H, NH), 8.68ꢁ8.67 (m, 1H, ArH), 8.25 (d, 1H, J = 8.4
Hz, ArH), 7.94 (d, 1H, J = 9.2 Hz, ArH), 7.52 (d, 1H, J =8.8 Hz,
ArH), 7.38ꢁ7.35 (m, 1H, ArH), 7.02 (s, 1H, ArH), 6.72 (d, 1H, J
= 8.0 Hz, ArH), 6.46 (d, 1H, J = 8.4 Hz, ArH), 5.67 (s, 1H, CH),
5.00ꢁ4.89 (m, 2H, CH2), 3.68 (s, 3H, OCH3), 3.62 (s, 3H,
OCH3). Anal. Calcd for C22H18N2O4: C, 70.58; H, 4.85; N, 7.48;
Found C, 70.68; H, 4.80; N, 7.50.
11-(3-Nitrophenyl)-8,11-dihydrofuro[3,4-b][4,7]phenan-
throlin-10(7H)-one (4g). This compound was obtained
according to above general procedure, mp>300 °C; ir (potassium
bromide): 3230, 3111, 3073, 1723, 1649, 1607, 1469, 1431,
1301, 1247, 1158, 1072, 964, 733 cm-1; 1H nmr: ꢀ 10.60 (s, 1H,
NH), 8.70ꢁ8.69 (m, 1H, ArH), 8.23 (d, 1H, J = 8.8 Hz, ArH),
6.10 (s, 1H, ArH), 8.02ꢁ7.98 (m, 2H, ArH), 7.66 (d, 1H, J = 7.6
Hz, ArH), 7.59ꢁ7.51 (m, 2H, ArH), 7.39ꢁ7.36 (m, 1H, ArH),
6.03 (s, 1H, CH), 5.05ꢁ4.94 (m, 2H, CH2). Anal. Calcd for
C20H13N3O4: C, 66.85; H, 3.65; N, 11.69. Found C, 66.93; H,
3.58; N, 11.56.
11-(Benzo[d][1,3]dioxo-5-yl)-8,11-dihydrofuro[3,4-b][4,7]-
phenanthrolin-10(7H)-one (4h). This compound was obtained
according to above general procedure, mp>300 °C; ir (potassium
bromide): 3184, 3111, 3066, 1721, 1649, 1610, 1469, 1438,
1353, 1258, 1165, 1039, 965, 753 cm-1; 1H nmr: ꢀ 10.44 (s, 1H,
NH), 8.69ꢁ8.68 (m, 1H, ArH), 8.26 (d, 1H, J = 8.4 Hz, ArH),
7.94 (d, 1H, J = 8.8 Hz, ArH), 7.51 (d, 1H, J = 8.8 Hz, ArH),
7.40ꢁ7.37 (m, 1H, ArH), 6.79 (s, 1H, ArH), 6.72 (d, 1H, J = 8.0
Hz, ArH), 6.61 (d, 1H, J = 8.0 Hz, ArH), 5.92-5.89(m, 2H, CH2),
5.66 (s, 1H, CH), 5.01ꢁ4.89 (m, 2H, CH2). Anal. Calcd for
C21H14N2O4: C, 70.39; H, 3.94; N, 7.82. Found C, 70.32; H,
3.95; N, 7.80.
11-(4-Fluorophenyl)-8,11-dihydrofuro[3,4-b][4,7]phenan-
throlin-10(7H)-one (4a). This compound was obtained
according to above general procedure, mp>300 °C; ir (potassium
bromide): 3238, 3065, 3046, 1725, 1650, 1577, 1416, 1285,
1
1177, 1099, 961 cm-1; H nmr: ꢀ 9.63 (s, 1H, NH), 8.16ꢁ8.15
(m, 1H, ArH), 7.51 (d, 1H, J = 8.8 Hz, ArH), 7.42 (d, 1H, J = 8.8
Hz, ArH), 6.77ꢁ6.74 (m, 2H, ArH), 6.70ꢁ6.66 (m, 2H, ArH),
6.39ꢁ6.34 (m, 2H, ArH), 5.20 (s, 1H, CH), 4.35ꢁ4.26 (m, 2H,
CH2). Anal. Calcd for C20H13FN2O2: C, 72.28; H, 3.94; N, 8.43.
Found C, 72.36; H, 3.85; N, 8.35.
11-(4-Chlorophenyl)-8,11-dihydrofuro[3,4-b][4,7]phenan-
throlin-10(7H)-one (4b). This compound was obtained
according to above general procedure, mp>300 °C; ir (potassium
bromide): 3235, 3135, 3054, 2978, 1932, 1722, 1650, 1530,
1
1487, 1415, 1283, 1160, 1106, 962, 739, 696 cm-1; H nmr: ꢀ
9.61 (s, 1H, NH), 8.10ꢁ8.06 (m, 1H, ArH), 7.42 (d, 1H, J = 8.4
Hz, ArH), 7.34 (d, 1H, J = 8.8 Hz, ArH), 6.85 (d, 1H, J = 8.8 Hz,
ArH ), 6.73ꢁ6.66 (m, 1H, ArH), 6.60ꢁ6.55 (m, 4H, ArH), 5.10
(s, 1H, CH), 4.27ꢁ4.19 (m, 2H, CH2). Anal. Calcd for
C20H13ClN2O2: C, 68.87; H, 3.76; N, 8.03. Found C, 68.95; H,
3.65; N, 7.96.
11-(4-Bromophenyl)-8,11-dihydrofuro[3,4-b][4,7]phenan-
throlin-10(7H)-one (4c). This compound was obtained
according to above general procedure, mp>300 °C; ir (potassium
bromide): 3233, 3135, 3051, 1721, 1650, 1592, 1577, 1531,
1
1439, 1282, 1180, 1070, 962, 688 cm-1; H nmr: ꢀ 9.60 (s, 1H,
NH), 8.10ꢁ8.00 (m, 1H, ArH), 7.36 (d, 1H, J = 8.4 Hz, ArH),
7.26 (d, 1H, J = 8.8 Hz, ArH), 6.80 (d, 1H, J = 8.8 Hz, ArH),
6.65ꢁ6.60 (m, 3H, ArH), 6.47 (d, 2H, J = 8.0 Hz, ArH), 5.02 (s,
1H, CH), 4.21ꢁ4.11 (m, 2H, CH2). Anal. Calcd for
C20H13BrN2O2: C, 61.09; H, 3.33; N, 7.12. Found C, 61.15; H,
3.26; N, 7.05.
11-p-Tolylfuro[3,4-b][4,7]phenanthrolin-10(7H,8H,11H)-
one (4i). This compound was obtained according to above
general procedure, mp>300 °C; ir (potassium bromide): 3218,
3135, 3046, 2931, 2858, 1723, 1649, 1593, 1468, 1352, 1286,
1
1175, 1011, 961, 829, 673 cm-1; H nmr: ꢀ 10.43 (s, 1H, NH),
8.68ꢁ8.67 (m, 1H, ArH), 8.21 (d, 1H, J = 8.8 Hz, ArH), 7.94 (d,

Jul-Aug 2008 Furo[3,4-b]-[4,7]phenanthroline and Indeno[2,1-b][4,7]phenanthroline Derivatives in Water
1069
1H, J = 8.8 Hz, ArH), 7.52 (d, 1H, J =8.8 Hz, ArH), 7.37ꢀ7.34
(m, 1H, ArH), 7.09 (d, 2H, J = 7.6 Hz, ArH), 7.00 (d, 2H, J =
7.6Hz, ArH), 5.67 (s, 1H, CH), 5.00ꢀ4.89 (m, 2H, CH2), 2.17(s,
3H, CH3). Anal. Calcd for C21H16N2O2: C, 76.81; H, 4.91; N,
8.53. Found C, 76.80; H, 4.88; N, 8.55.
3242, 3060, 1715, 1682, 1665, 1605, 1466, 1282, 1155, 1071,
1
1006, 930, 709 cm-1; H nmr: ꢁ 10.45 (s, 1H, NH), 8.88ꢀ8.87
(m, 1H, ArH), 8.35ꢀ8.28 (m, 2H, ArH), 8.09ꢀ8.07 (m, 1H,
ArH), 7.85ꢀ7.79 (m, 3H, ArH), 7.65ꢀ7.62 (m, 2H, ArH), 7.45
(d, 2H, J = 8.4 Hz, ArH), 7.38 (d, 1H, J = 8.4 Hz, ArH),
7.34ꢀ7.31 (m, 1H, ArH), 5.92 (s, 1H, CH). Anal. Calcd for
C25H15BrN2O: C, 68.35; H, 3.44; N, 6.38. Found C, 68.46; H,
3.32; N, 6.29.
11-Phenyl-8,11-dihydrofuro[3,4-b][4,7]phenanthrolin-
10(7H)-one (4j). This compound was obtained according to
above general procedure, mp>300 °C; ir (potassium bromide):
3273, 3143, 3063, 2935, 2870, 1727, 1652, 1579, 1508, 1397,
13-(4-Methoxyphenyl)-7H-indeno[2,1-b][4,7]phenanthrol-
in-12(13H)-one (6d). This compound was obtained according to
above general procedure, mp>300 °C; ir (potassium bromide):
3248, 3040, 1713, 1678, 1664, 1573, 1439, 1256, 1155, 1057,
1
1292, 1181, 1127, 962, 759, 701 cm-1; H nmr: ꢁ 10.46 (s, 1H,
NH), 8.68ꢀ8.67 (m, 1H, ArH), 8.22 (d, 1H, J = 8.4 Hz, ArH),
7.95 (d, 1H, J = 8.8 Hz, ArH), 7.53 (d, 1H, J = 8.8 Hz, ArH),
7.38ꢀ7.35 (m, 1H, ArH), 7.22ꢀ7.19 (m, 4H, ArH), 7.10ꢀ7.06
(m, 1H, ArH), 5.73 (s, 1H, CH), 5.01ꢀ4.91 (m, 2H, CH2). Anal.
Calcd for C20H14N2O2: C, 76.42; H, 4.49; N, 8.91. Found C,
76.56; H, 4.42; N, 8.82.
1
1006, 937, 847 cm-1; H nmr: ꢁ 10.40 (s, 1H, NH), 8.86ꢀ8.85
(m, 1H, ArH), 8.33ꢀ8.24 (m, 2H, ArH), 8.08ꢀ8.06 (m, 2H,
ArH), 7.87ꢀ7.81 (m, 2H, ArH), 7.77ꢀ7.70 (m, 3H, ArH), 7.58
(d, 2H, J = 8.4 Hz, ArH), 7.36ꢀ7.30 (m, 1H, ArH), 5.94 (s, 1H,
CH), 3.63(s, 3H, OCH3). Anal. Calcd for C26H18N2O2: C, 79.98;
H, 4.65; N, 7.17. Found C, 79.95; H, 4.60; N, 7.20.
11-(4-Hydroxy-3-nitrophenyl)-8,11-dihydrofuro[3,4-b]-
[4,7]phenanthrolin-10(7H)-one (4k). This compound was
obtained according to above general procedure, mp>300 °C; ir
(potassium bromide): 3218, 3064, 1722, 1649, 1607, 1468,
13-(2,4-Dichlorophenyl)-7H-indeno[2,1-b][4,7]phenan-
throlin-12(13H)-one (6e). This compound was obtained
according to above general procedure, mp>300 °C; ir (potassium
bromide): 3240, 3050, 1715, 1610, 1568, 1508, 1426, 1375,
1
1431, 1330, 1235, 1135, 1078, 828, 753 cm-1; H nmr: ꢁ 10.83
(s, 1H, OH), 10.52 (s, 1H, NH), 8.70ꢀ8.69 (m, 1H, ArH), 8.24
(d, 1H, J = 8.4 Hz, ArH), 7.97 (d, 1H, J = 9.2 Hz, ArH), 7.73 (s,
1H, ArH), 7.54 (d, 1H, J = 8.8 Hz, ArH), 7.41ꢀ7.35 (m, 2H,
ArH), 6.99 (d, 1H, J = 8.8 Hz, ArH), 5.82 (s, 1H, CH),
5.03ꢀ4.92 (m, 2H, CH2). Anal. Calcd for C20H13N3O5: C, 64.00;
H, 3.49; N, 11.20. Found C, 64.03; H, 3.52; N, 11.25.
1
1262, 1140, 1066, 933, 846 cm-1; H nmr: ꢁ 10.36 (s, 1H, NH),
8.87ꢀ8.86 (m, 1H, ArH), 8.35ꢀ8.32 (m, 2H, ArH), 8.05 (d, 1H, J
= 7.6 Hz, ArH), 7.80 (s, 1H, ArH), 7.74ꢀ7.68 (m, 2H, ArH),
7.65ꢀ7.62 (m, 2H, ArH), 7.50 (d, 2H, J = 8.4 Hz, ArH),
7.35ꢀ7.30 (m, 1H, ArH), 5.99 (s, 1H, CH). Anal. Calcd for
C25H14Cl2N2O: C, 69.94; H, 3.29; N, 6.53. Found C, 69.90; H,
3.30; N, 6.55.
11-(Thiophen-2-yl)-8,11-dihydrofuro[3,4-b][4,7]phenan-
throlin-10(7H)-one (4l). This compound was obtained
according to above general procedure, mp>300 °C; ir (potassium
bromide): 3261, 3146, 3064, 1724, 1665, 1614, 1467, 1430,
1356, 1257, 1165, 1074, 960, 752 cm-1; 1H nmr: ꢁ 10.54 (s, 1H,
NH), 8.73ꢀ8.72 (m, 1H, ArH), 8.41 (d, 1H, J = 8.4 Hz, ArH),
7.96 (d, 1H, J = 8.8 Hz, ArH), 7.51 (d, 1H, J = 9.2 Hz, ArH),
7.45-7.42 (m, 1H, ArH), 7.23ꢀ7.22 (m, 1H, ArH), 6.92 (s, 1H,
ArH), 6.85ꢀ6.84 (m, 1H, ArH), 6.09 (s, 1H, CH), 5.05ꢀ4.93 (m,
2H, CH2). Anal. Calcd for C18H12N2O2S: C, 67.48; H, 3.78; N,
8.74; S, 10.01. Found C, 67.45; H, 3.80; N, 8.72; S, 10.00.
13-(4-Fluorophenyl)-7H-indeno[2,1-b][4,7]phenanthrolin-
12(13H)-one (6a). This compound was obtained according to
above general procedure, mp>300 °C; ir (potassium bromide):
3230, 3043, 1714, 1608, 1577, 1504, 1433, 1373, 1259, 1144,
1076, 929, 878 cm-1; 1H nmr: ꢁ 10.53 (s, 1H, NH), 8.86ꢀ8.85 (m,
1H, ArH), 8.32ꢀ8.25 (m, 2H, ArH), 8.06 (d, 1H, J = 7.6 Hz,
ArH), 7.80ꢀ7.78 (m, 1H, ArH), 7.67ꢀ7.60 (m, 3H, ArH),
7.54ꢀ7.45 (m, 4H, ArH), 7.31ꢀ7.27 (m, 1H, ArH), 5.82 (s, 1H,
CH). Anal. Calcd for C25H15FN2O: C, 79.35; H, 4.00; N, 7.40.
Found C, 79.46; H, 3.95; N, 7.35.
13-(3,4-Dimethoxyphenyl)-7H-indeno[2,1-b][4,7]phenan-
throlin-12(13H)-one (6f). This compound was obtained
according to above general procedure, mp>300 °C; ir (potassium
bromide): 3236, 3088, 1713, 1685, 1611, 1571, 1458, 1203,
1
1150, 1055, 1004, 743, 654 cm-1; H nmr: ꢁ 10.43 (s, 1H, NH),
8.71 (s, 1H, ArH), 8.20 (d, 1H, J = 7.6 Hz, ArH), 8.09ꢀ8.03 (m,
3H, ArH), 7.70ꢀ7.59 (m, 3H, ArH), 7.52 (d, 2H, J = 8.4 Hz,
ArH), 7.33ꢀ7.30 (m, 2H, ArH), 5.90 (s, 1H, CH), 3.76 (s, 3H,
OCH3), 3.68 (s, 3H, OCH3). Anal. Calcd for C27H20N2O3: C,
77.13; H, 4.78; N, 6.66. Found C, 77.15; H, 4.80; N, 6.70.
13-(3-Nitrophenyl)-7H-indeno[2,1-b][4,7]phenanthro-
lin-12(13H)-one (6g). This compound was obtained according
to above general procedure, mp>300 °C; ir (potassium bromide):
3233, 3087, 1716, 1684, 1664, 1604, 1457, 1260, 1157, 1078,
1
1006, 936, 700 cm-1; H nmr: ꢁ 10.50 (s, 1H, NH), 8.89ꢀ8.88
(m, 1H, ArH), 8.54ꢀ8.52 (m, 2H, ArH), 8.40ꢀ8.33 (m, 2H,
ArH), 8.13ꢀ8.11 (m, 1H, ArH), 7.92ꢀ7.82 (m, 3H, ArH),
7.71ꢀ7.62 (m, 3H, ArH), 7.30ꢀ7.27 (m, 1H, ArH), 6.03 (s, 1H,
CH). Anal. Calcd for C25H15N3O3: C, 74.07; H, 3.73; N, 10.36.
Found C, 74.10; H, 3.75; N, 10.35.
13-(4-Chlorophenyl)-7H-indeno[2,1-b][4,7]phenanthrolin-
12(13H)-one (6b). This compound was obtained according to
above general procedure, mp>300 °C; ir (potassium bromide):
3238, 3043, 1714, 1608, 1577, 1504, 1433, 1373, 1259, 1144,
13-(Benzo[d][1,3]dioxo-6-yl)-7H-indeno[2,1-b][4,7]phen-
anthrolin-12(13H)-one (6h). This compound was obtained
according to above general procedure, mp>300 °C; ir (potassium
bromide): 323O, 3089, 1712, 1688, 1660, 1601, 1450, 1268,
1
1076, 923, 856 cm-1; H nmr: ꢁ 10.35 (s, 1H, NH), 8.88ꢀ8.87
1
(m, 1H, ArH), 8.36ꢀ8.30 (m, 2H, ArH), 8.09 (d, 1H, J = 7.6 Hz,
ArH), 7.83ꢀ7.80 (m, 1H, ArH), 7.75ꢀ7.68 (m, 3H, ArH),
7.66ꢀ7.61 (m, 2H, ArH), 7.52 (d, 2H, J = 8.4 Hz, ArH),
7.35ꢀ7.31 (m, 1H, ArH), 6.00 (s, 1H, CH). Anal. Calcd for
C25H15ClN2O: C, 76.05; H, 3.83; N, 7.09. Found C, 76.13; H,
3.75; N, 7.00.
13-(4-Bromophenyl)-7H-indeno[2,1-b][4,7]phenanthrolin-
12(13H)-one (6c). This compound was obtained according to
above general procedure, mp>300 °C; ir (potassium bromide):
1159, 1088, 1006, 960, 746 cm-1; H nmr: ꢁ 10.39 (s, 1H, NH),
8.86ꢀ8.85 (m, 1H, ArH), 8.32ꢀ8.28 (m, 1H, ArH), 8.07 (d, 1H, J
= 8.0 Hz, ArH), 7.83ꢀ7.80 (m, 3H, ArH), 7.66 (s, 1H, ArH) ,
7.54ꢀ7.45 (m, 4H, ArH), 7.33ꢀ7.30 (m, 1H, ArH), 5.90 (s, 1H,
CH), 5.01-4.89(m, 2H,CH2). Anal. Calcd for C26H16N2O3: C,
77.22; H, 3.99; N, 6.93. Found C, 77.20; H, 3.95; N, 6.96.
13-p-Tolyl-7H-indeno[2,1-b][4,7]phenanthrolin-12(13H)-
one (6i). This compound was obtained according to above
general procedure, mp>300 °C; ir (potassium bromide): 3234,

1070
F. Shi, D. Zhou, S. Tu, Q. Shao, C. Li, L. Cao
Vol 45
2002, 35, 717; (b) Kappe, C. O. Angew. Chem., Int. Ed. 2004, 43, 6250;
(c) Olofsson, K.; Larhed, M. in Microwave Assisted Organic Synthesis,
Tierney, J. P. and Lidström, P. Eds, 2005, pp. 23–43; (d) Kappe, C. O.;
Dallinger, D. Nat. Rev. Drug Discovery 2006, 5, 51.
[5] Wu, X.; Ekegren, J. K.; Larhed, M. Organometallics 2006,
25, 1434.
[6] (a) Gronnow, M. J.; White, R. J.; Clark, J. H.; Macquarrie, D.
J. Org. Process Res. Dev. 2005, 9, 516; (b) Blettner, C. G.; König, W.
A.; Stenzel, W.; Schotten, T. J. Org. Chem. 1999, 64, 3885; (c)
Leadbeater, N. E.; Marco, M. Org. Lett. 2002, 4, 2973; (d) Bagnell, L.;
Cablewski, T.; Strauss, C. R.; Trainor, R. W. J. Org. Chem. 1996, 61,
7355.
[7] New, J. S.; Christopher, W. L.; Yevich, J. P.; Butler, R.;
Schlemmer Jr Francis, R.; VanderMaelen, C. P.; Cipollina, J. A. J. Med.
Chem. 1989, 32, 1147.
[8] Wagner, G.; Prantz, J. Pharmazie 1993, 48, 250.
[9] Bukoski, R. D.; Bo, J.; Xue, H.; Bian, K. J. Pharmacol. Exp.
Ther. 1993, 265, 30.
[10] Paronikyan, E. G.; Oganisyan, A. Kh.; Noravyan, A. S.;
Paronikyan, R. G.; Dzhagatspanyan, I. A. Pharm. Chem. J. 2002, 36,
413.
[11] Jeschke, P.; Harder, A.; Etzel, W.; Gau, W.; Goehrt, A.;
BenetBuchholz, J.; Thielking, G. Bioorg. Med. Chem. Lett. 2005, 15,
2375.
[12] Gerster, P.; Riegger, C.; Fallert, M. Arzneim. Forsch. 1987,
37, 309.
[13] Wishka, D. G.; Graber, D. R.; Seest, E. P.; Dolak, L. A.; Han,
F.; Watt, W.; Morris, J. J. Org. Chem. 1998, 63, 7851.
[14] Marco, J. L.; Carreiras, M. C.;. Mini-Rev. Med. Chem. 2003,
3, 518.
[15] Hofmann, A. in “Die Mutterkornalkaloide”, Ferdinand Enke
Verlag, Stuttgart, Germany ,1964.
[16] Cassady, J. M.; Floss, H. G. Lloydia 1977, 40, 90.
[17] Jastrzebska-Glapa, M.; Mlochowski, J.; Sliwa, W. Pol. J.
Chem. 1979, 53, 811.
[18] (a) Hickson, C. L.; McNab, H. Synthesis 1981, 464; (b)
Wiersum, U. E.; Eldred, C. D.; Vrijhof, P.; VanderPlas, H. C.
Tetrahedron Lett. 1977, 18, 1741; (c) Marchenko, N. B.; Granik, V. G.
Khim. Geterotsikl. Soedin. 1982, 68-71; (d) Mavoungou-Gomes, L.;
Bruneton, J.; Aicart, M. J. Heterocycl. Chem. 1985, 22, 1233; (e) Rose,
U. Arzneimittel-Forschung 1991, 41, 199; (f) Del Bosque, J. R.; Martin,
N.; Mora, A.; Morales, A.; Quinteiro, M.; Seoane, C.; Soto, J. L.;
Suarez, M. Anales de Quimica 1994, 90, 511; (g) Tratrat, C.; Giorgi-
Renault, S.; Husson, H. P. Org. Lett. 2002, 4, 3187.
[19] (a) Gusak, K. N.; Tereshko, A. B.; Kozlov, N. G. Russ. J.
Org. Chem. 2001, 37, 1495; (b) Gusak, K. N.; Kozlov, N. G.; Tereshko,
A. B. Russ. J. Org. Chem. 2004, 40, 1322; (c) Kozlov, N. G.; Gusak, K.
N.; Tereshko, A. B.; Firgang, S. I.; Shashkov, A. S. Russ. J. Org. Chem.
2004, 40, 1181; (d) Kadutskii, A. P.; Kozlov, N. G. Russ. J. Org. Chem.
2006, 42, 1388.
3026, 1714, 1606, 1575, 1507, 1457, 1371, 1260, 1153, 1077,
1
929, 846 cm-1; H nmr: ꢀ 10.41 (s, 1H, NH), 8.88ꢁ8.87 (m, 1H,
ArH), 8.35ꢁ8.30 (m, 2H, ArH), 8.06 (d, 1H, J = 8.0 Hz, ArH),
7.85-7.78 (m, 2H, ArH), 7.66ꢁ7.61 (m, 2H, ArH), 7.46 (d, 2H, J
= 8.4 Hz, ArH), 7.36ꢁ7.30 (m, 3H, ArH), 6.00 (s, 1H, CH).
Anal. Calcd for C26H13N2O: C, 83.40; H, 4.85; N, 7.48. Found C,
83.42; H, 4.86; N, 7.52.
13-Phenyl-7H-indeno[2,1-b][4,7]phenanthrolin-12(13H)-
one (6j). This compound was obtained according to above
general procedure, mp>300 °C; ir (potassium bromide): 3238,
3043, 1714, 1608, 1577, 1504, 1433, 1373, 1259, 1144, 1076,
1
923, 856 cm-1; H nmr: ꢀ 10.41 (s, 1H, NH), 8.85ꢁ8.84 (m, 1H,
ArH), 8.36ꢁ8.29 (m, 2H, ArH), 8.11 (d, 1H, J = 7.2 Hz, ArH),
7.83ꢁ7.80 (m, 1H, ArH), 7.69ꢁ7.60 (m, 5H, ArH), 7.47ꢁ7.45
(m, 1H, ArH), 7.41ꢁ7.34 (m, 1H, ArH), 7.28ꢁ7.25 (m, 1H,
ArH), 7.22ꢁ7.16 (m, 1H, ArH), 5.83 (s, 1H, CH). Anal. Calcd
for C25H16N2O: C, 83.31; H, 4.47; N, 7.77. Found C, 83.45; H,
4.38; N, 7.65.
13-(4-Hydroxy-3-nitrophenyl)-7H-indeno[2,1-b][4,7]phen-
anthrolin-12(13H)-one (6k). This compound was obtained
according to above general procedure, mp>300 °C; ir (potassium
bromide): 3236, 3080, 1715, 1668, 1580, 1518, 1444, 1393,
1
1260, 1122, 1060, 940, 860 cm-1; H nmr: ꢀ 10.80 (s, 1H, OH),
10.48 (s, 1H, NH), 8.87ꢁ8.86 (m, 1H, ArH), 8.51ꢁ8.47 (m, 2H,
ArH), 8.32 (d, 2H, J = 8.4 Hz, ArH), 8.12 (s, 1H, ArH),
7.88ꢁ7.70 (m, 2H, ArH), 7.66ꢁ7.60 (m, 2H, ArH), 7.50ꢁ7.22
(m, 2H, ArH), 6.02 (s, 1H, CH). Anal. Calcd for C25H15N3O4: C,
71.25; H, 3.59; N, 9.97. Found C, 71.30; H, 3.60; N, 9.95.
13-(Thiophen-2-yl)-7H-indeno[2,1-b][4,7]phenanthrolin-
12(13H)-one (6l). This compound was obtained according to
above general procedure, mp>300 °C; ir (potassium bromide):
3235, 3050, 1712, 1653, 1578, 1472, 1396, 1255, 1157, 1077,
1
945, 847 cm-1; H nmr: ꢀ 10.40 (s, 1H, NH), 8.90ꢁ8.89 (m, 1H,
ArH), 8.34ꢁ8.28 (m, 2H, ArH), 8.09 (d, 1H, J = 7.6 Hz, ArH),
7.99ꢁ7.98 (m, 1H, ArH), 7.81 (t, 1H, J = 7.2 Hz, ArH),
7.76ꢁ7.69 (m, 2H, ArH), 7.63 (t, 1H, J = 7.2 Hz, ArH),
7.40ꢁ7.33 (m, 3H, ArH), 5.99 (s, 1H, CH). Anal. Calcd for
C23H14N2OS: C, 75.39; H, 3.85; N, 7.64; S, 8.75. Found C,
75.35; H, 3.88; N, 7.65; S, 8.78.
Acknowledgement. We are grateful for financial support
from the National Science Foundation of China (No. 20672090)
and Natural Science Foundation of the Jiangsu Province (No.
BK2006033), Six Kinds of Professional Elite Foundation of the
Jiangsu Province (No. 06-A-039).
[20] Safak, C.; Simsek, R.; Altas, Y.; Boydag, S.; Erol, K. Boll.
Chim. Farm. 1997, 136, 665.
REFERENCES
[21] Bisenieks, E.; Uldrikis, J.; Kirule, I.; Tirzite, G.; Dubur, G.
Khim. Geterotsikl. Soedin. 1982, 1528.
[22] (a) Augstein, J.; Ham, A. L.; Leeming, P. R. J. Med. Chem.
1972, 15, 466; (b) Kunstmann, R.; Fischer, G. J. Med. Chem. 1984, 27,
1312; (c) Kunstmann, R.; Lerch, U.; Gerhards, H.; Leven, M.; Schacht,
U. J. Med. Chem. 1984, 27, 432.
[23] Rentzea, C.; Meyer, N.; Kast, J.; Plath, P.; Koenig, H.;
Harreus, A.; Kardorff, U.; Gerber, M.; Walter, H. Ger. Offen. DE
4301426 A1 1994, 21; Chem. Abstr. 1994, 121, 133986.
[24] (a) Van Emelen, K.; De Wit, T.; Hoornaert, G. J.;
Compernolle, F. Tetrahedron 2002, 58, 4225; (b) De Wit, T.; Van
Emelen, K.; Maertens, F.; Hoornaert, G. J.; Compernolle, F.
Tetrahedron Lett. 2001, 42, 4919.
[25] (a) Kappe, C. O. Angew. Chem., Int. Ed. 2004, 43, 6250; (b)
Perreux, L.; Loupy, A. Tetrahedron 2001, 57, 9199; (c) Loupy, A. C. R.
Chim. 2004, 7, 103.
[1] (a) Sinou, D. Top. Curr. Chem. 1999, 41, 206; (b) Strauss, C.
R.; Trainor, R. W. Aust. J. Chem. 1995, 48, 1665; (c) An, J.; Bagnell, L.;
Cablewski, T.; Strauss, C. R.; Trainor, R. W. J. Org. Chem. 1997, 62,
2505; (d) Beletskaya, I. P.; Cheprakov, A. V. in Organic synthesis in
water, Grieco, P. A. Ed, 1998, pp. 141–222; (e) Li, C.-J. Chem. Rev.
2005, 105, 3095; (f) Arvela, R. K.; Leadbeater, N. E.; Collins, M. J.
Tetrahedron 2005, 61, 9349; (g) Wu, X.; Larhed, M. Org. Lett. 2005, 7,
3327; (h) Kormos, C. M.; Leadbeater, N. E. Tetrahedron 2006, 62,
4728; (i) Arvela, R. K.; Leadbeater, N. E. J. Org. Chem. 2005, 70, 1786.
[2] Andrade, C. K. Z.; Alves, L. M. Curr. Org. Chem. 2005, 9,
195.
[3] (a) Genet, J. P.; Savignac, M. J. Organomet. Chem. 1999,
576, 305; (b) Shaughnessy, K. H.; Devasher, R. B. Curr. Org. Chem.
2005, 9, 585; (c) Leadbeater, N. E. Chem. Commun. 2005, 2881.
[4] (a) Larhed, M.; Moberg, C.; Hallberg, A. Acc. Chem. Res.