An efficient and facile microwave-assisted synthesis of benzo[b][4,7]phenanthroline derivatives in water

Article abstract of DOI:10.1002/jhet.5570450217

(Chemical Equation Presented) A series of benzo[b][4,7]phenanthroline derivatives were synthesized via a three-component reaction of aromatic aldehydes, 6-aminoquinoline and either 1,3-cyclohexanedione or dimedone in water under microwave irradiation with

Full text of DOI:10.1002/jhet.5570450217

Mar-Apr 2008
405
An Efficient and Facile Microwave-assisted Synthesis of
Benzo[b][4,7]phenanthroline Derivatives in Water
Feng Shi, Dianxiang Zhou, Chunmei Li, Qingqing Shao, Longji Cao, Shujiang Tu*
School of Chemistry and Chemical Engineering, Xuzhou Normal University, Key Laboratory of Biotechnology
for Medicinal Plant, Xuzhou, Jiangsu, 221116, P. R. China
Received May 14, 2007
R
O
O
O
N
H2N
R1
R1
water
MWI
RCHO
+
+
R1
R1
N
N
H
1
3
2
4
A series of benzo[b][4,7]phenanthroline derivatives were synthesized via a three-component reaction of
aromatic aldehydes, 6-aminoquinoline and either 1,3-cyclohexanedione or dimedone in water under
microwave irradiation without use of any catalyst. This method has the advantages of short reaction time,
high yields, low cost and environmental friendliness as well as easy operation.
J. Heterocyclic Chem., 45, 405 (2008).
INTRODUCTION
desirable. Interested in the bioactivities of the 4,7-
phenanthroline skeleton and clean reaction procedure, we
would like to report a facile, rapid and green methodology
for the synthesis of benzo[b][4,7]phen-anthroline
derivatives by three-component condensations in water
under microwave irradiation (Scheme 1).
Organic reactions in water have become an important
research area. Many reactions have been accomplished in
aqueous medium, such as Michael reaction [1], Claisen
rearrangement [2], Mannich reaction [3], Reformatsky
reaction [4], Tsuj-Trost reaction [5], Barbier-type reaction
[6], Aldol-Type reaction [7], Fries rearrangement reaction
[8] and Kröhnke reaction [9]. Water has therefore become
an attractive medium for many organic reactions, not only
for the advantages concerning the avoidance of expensive
drying reactants, catalysts and solvents, but also for some
unique reactivity and selectivity [10,11]. Similarly,
microwave-enhanced procedures have proved highly
useful in organic chemistry due to greater reaction control
and high reaction rates [12]. Under microwave irradiation
(MWI), water is rapidly heated to high temperatures,
enabling it to act as a less polar pseudo-organic solvent.
Moreover, precise control of the reaction temperature is
easily achieved because of the very high heat capacity of
water [13].
Compounds with the 4,7-phenanthroline motif which
are analogs of ergot alkaloids, possess high and versatile
pharmacological effects, such as serotonin antagonism,
vasoconstriction, oxytocic and psychotropic activities
[14]. And they are also used as inhibitors of the pituitary
hormone prolactin [15] and fungicides [16]. Hence, the
preparation of this heterocyclic unit has gained much
attention.
Scheme 1
R
O
O
O
N
H2N
R1
R1
water
MWI
RCHO
+
+
R1
R1
N
N
H
1
3
2
4
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 1,3-cyclohexanedione
(3, 1.0 mmol) was examined using glycol, glacial acetic
acid, ethanol and N,N-dimethylformamide as solvent (2.0
mL) at 100 °C, respectively. All reactions were carried
out at the maximum power of 250 W. The results were
summarized in Table 1.
It is 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 (Entries 1−5, Table 1). Considering environ-
mental friendliness and the avoidance of using toxic
organic reagents, water was chosen as the solvent for all
further microwave-assisted reactions.
Kozlov Gusak [17] and co-workers have reported the
synthesis of 4,7-phenanthroline derivatives using 1-
butanol as solvent by refluxing, the procedure was
complicated and toxic reagents such as benzene were
used. Therefore, the development of a simple and clean
method for the preparation of this skeleton is still strongly

406
F. Shi, D. Zhou, C. Li, Q. Shao, L. Cao, S. Tu
Vol 45
Although the detailed mechanism of the above reaction
remains to be fully clarified, the formation of benzo-
[b][4,7]phenanthrolin 4 could be explained by a possible
reaction sequence presented in Scheme 2. The product 4
may be synthesized via sequential condensation, addition,
cyclization and elimination. The condensation between
aldehydes 1 and 1,3-cyclohexanedione or dimedone 3
lead to intermediate 5, Michael addition between 5 and 2
would give 6, which upon intermolecular cyclization and
dehydration, would generate the product 4.
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.
In this study, all the products were characterized by
1
mp, IR and H NMR spectral data as well as elemental
Table 1
analyses. Furthermore, the structure of 4d [18] was
established by X-ray crystallographic analysis. The
molecular structure of 4d was shown in Figure 1.
Optimization of reaction conditions of compound 4a
Entry
Solvent
T / °C
Time / min
Yield / %
1
2
3
4
5
6
7
8
Glycol
HOAc
EtOH
water
DMF
water
water
water
water
water
100
100
100
100
100
90
110
120
130
140
10
12
14
10
13
12
9
8
8
8
89
80
79
88
75
84
90
91
90
89
9
10
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 (Table 2). When the power was at
100−200 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.
Figure 1. ORTEP diagram of 4d.
In summary, we have developed a three-component
reaction of an aldehyde, 6-aminoquinoline and either 1,3-
cyclohexanedione or dimedone in high-temperature water,
and have shown its application to the synthesis of a
number of benzo[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.
Table 2
Power optimization of reaction conditions of compound 4a under
microwave irradiation.
Entry
Power / W
Time / min
Yield / %
1
2
3
4
5
100
150
200
250
300
8
8
8
8
8
79
83
86
91
90
EXPERIMENTAL
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 uncorrected. IR spectra were taken on a FT-IR-Tensor
The use of these optimal microwave experimental
conditions [water, 120 °C, 250 W (Maximum power)]
for the reactions of different aromatic aldehydes
afforded good yields of benzo[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 able to
affect the synthesis of compounds 4. Moreover, a
heterocyclic aldehyde, thiophene-2-carbaldehyde (Table
3, entries 12), still showed high reactivity and clean
reaction under these standard conditions.
1
27 spectrometer in KBr pellets and reported in cm-1. H 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.
General procedure for the one-pot synthesis of benzo[b]-
[4,7]phenanthroline derivatives 4 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-
cyclohexanedione or dimedone 3 (1 mmol) and water (2 mL)

Mar-Apr 2008
An Efficient and Facile Microwave-assisted Synthesis of Benzo[b][4,7]phenanthroline
407
Table 3
Synthesis of 4 under microwave irradiation at 120 °C
Mp /
Entry
Product
R
R1
Time / min
Yield / %
°C
1
2
4a
4b
4c
4d
4e
4f
4-FC6H4
4-ClC6H4
H
H
8
7
6
6
7
8
9
6
5
5
9
8
9
8
7
5
9
8
5
7
7
9
8
6
91
93
94
95
94
92
90
95
96
97
90
91
93
92
94
95
91
92
95
93
93
92
93
94
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
3
4-BrC6H4
H
4
4-CH3OC6H4
2,4-Cl2C6H3
3,4-(CH3O)2C6H3
3-NO2C6H4
3,4-OCH2OC6H3
2-ClC6H4
H
5
H
6
H
7
4g
4h
4i
H
8
H
9
H
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
4j
C6H5
H
4k
4l
4-OH-3-NO2C6H3
thiophen-2-yl
4-FC6H4
H
H
4m
4n
4o
4p
4q
4r
4s
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
4-ClC6H4
4-BrC6H4
4-CH3OC6H4
2,4-Cl2C6H3
3,4-(CH3O)2C6H3
3-NO2C6H4
3,4-OCH2OC6H3
2-ClC6H4
4t
4u
4v
4w
4x
C6H5
4-OH-3-NO2C6H3
thiophen-2-yl
Scheme 2
O
O
R
O
O
N
NH2
R1
R1
CHR
+
+
RCHO
R1
R1
O
N
R1
R1
NH
O
1
3
5
2
6
O
R
O
O
R
O
R
N
N
N
- H2O
R1
R1
R1
N
H
N
H
R1
NH2
HO
R1
R1
4
8
7
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 benzo[b][4,7]-phenanthroline
derivatives 4.
ArH), 8.34 (d, 1H, J = 8.4 Hz, ArH), 7.89 (d, 1H, J = 8.8 Hz,
ArH), 7.56 (d, 1H, J = 9.2 Hz, ArH), 7.38-7.41 (m, 1H, ArH),
7.23-7.26 (m, 2H, ArH), 6.96 (t, 2H, J = 8.8 Hz, ArH), 5.85 (s,
1H, CH), 2.62 (s, 2H, CH2), 2.25-2.28 (m, 2H, CH2), 1.76-1.95
(m, 2H, CH2). Anal. calcd for C22H17FN2O: C, 76.73; H, 4.98; N,
8.13. Found: C, 76.70; H, 4.99; N, 8.10.
12-(4-Chlorophenyl)-9,10-dihydrobenzo[b][4,7]phenan-
throlin-11(7H,8H,12H)-one (4b). This compound was obtained
as yellow solid (95% ethanol), mp>300 °C; ir (potassium
bromide): 3251, 3069, 3023, 1603, 1515, 1489, 1387, 1281,
1189, 1091, 961cm-1; 1H nmr: δ 9.95 (s, 1H, NH), 8.67-8.68 (m,
1H, ArH), 8.32 (d, 1H, J = 8.8 Hz, ArH), 7.90 (d, 1H, J = 8.8
12-(4-Fluorophenyl)-9,10-dihydrobenzo[b][4,7]phenan-
throlin-11(7H,8H,12H)-one (4a). This compound was obtained
as yellow solid (95% ethanol), mp>300 °C; ir (potassium
bromide): 3257, 3066, 3022, 1603, 1514, 1426, 1386, 1280,
1
1187, 1093, 961cm-1; H nmr: δ 9.95 (s, 1H, NH), 8.67 (s, 1H,

408
F. Shi, D. Zhou, C. Li, Q. Shao, L. Cao, S. Tu
Vol 45
Hz, ArH), 7.56 (d, 1H, J = 9.2 Hz, ArH), 7.39-7.42 (m, 1H,
ArH), 7.19-7.25 (m, 4H, ArH), 5.84 (s, 1H, CH), 2.61-2.62 (m,
2H, CH2), 2.22-2.34 (m, 2H, CH2), 1.77-1.94 (m, 2H, CH2).
Anal. calcd for C22H17ClN2O: C, 73.23; H, 4.75; N, 7.76. Found
C, 73.25; H, 4.74; N, 7.75.
12-(Benzo[d][1,3]dioxol-5-yl)-9,10-dihydrobenzo[b][4,7]-
phenanthrolin-11(7H,8H,12H)-one (4h). This compound was
obtained as yellow solid (95% ethanol), mp>300 °C; ir
(potassium bromide): 3254, 3192, 3100, 1656, 1603, 1517,
1466, 1335, 1236, 1133, 1040, 963, 812 cm-1; 1H nmr: δ 9.88 (s,
1H, NH), 8.67-8.68 (m, 1H, ArH), 8.36 (d, 1H, J = 8.8 Hz,
ArH), 7.88 (d, 1H, J = 9.2 Hz, ArH), 7.55 (d, 1H, J = 9.2 Hz,
ArH), 7.40-7.43 (m, 1H, ArH), 6.79 (s, 1H, ArH), 6.60-6.67 (m,
2H, ArH), 5.86-5.88 (m, 2H, CH2), 5.76 (s, 1H, CH), 2.62 (s,
2H, CH2), 2.25-2.26 (m, 2H, CH2), 1.78-1.96 (m, 2H, CH2).
Anal. calcd for C23H18N2O3: C, 74.58; H, 4.90; N, 7.56. Found C,
74.60; H, 4.88; N, 7.60.
12-(2-Chlorophenyl)-9,10-dihydrobenzo[b][4,7]phenan-
throlin-11(7H,8H,12H)-one (4i). This compound was
obtained as yellow solid (95% ethanol), mp>300 °C; ir
(potassium bromide): 3251, 3069, 3023, 1603, 1515, 1489,
1387, 1281, 1189, 1091, 961 cm-1; 1H nmr: δ 10.00 (s, 1H,
NH), 8.66-8.67 (m, 1H, ArH), 8.48 (d, 1H, J = 8.4 Hz, ArH),
7.87 (d, 1H, J = 9.2 Hz, ArH), 7.54 (d, 1H, J = 8.8 Hz, ArH),
7.43-7.46 (m, 1H, ArH), 7.33 (d, 1H, J = 7.6 Hz, ArH), 7.25
(d, 1H, J = 8.0 Hz, ArH), 7.13 (t, 1H, J = 7.6 Hz, ArH), 7.05
(d, 1H, J = 7.2 Hz, ArH), 6.04 (s, 1H, CH), 2.64-2.66 (m, 2H,
CH2), 2.20-2.27 (m, 2H, CH2), 1.77-1.96 (m, 2H, CH2). Anal.
calcd for C22H17ClN2O: C, 73.23; H, 4.75; N, 7.76. Found C,
73.22; H, 4.76; N, 7.75.
12-(4-Bromophenyl)-9,10-dihydrobenzo[b][4,7]phenanthro-
lin-11(7H,8H,12H)-one (4c). This compound was obtained as
yellow solid (95% ethanol), mp>300 °C; ir (potassium bromide):
3250, 3190, 3096, 1602, 1514, 1464, 1336, 1236, 1141, 1099,
1
961, 802 cm-1; H nmr: δ 9.96 (s, 1H, NH), 8.67-8.68 (m, 1H,
ArH), 8.31 (d, 1H, J = 8.8 Hz, ArH), 7.90 (d, 1H, J = 8.8 Hz,
ArH), 7.56 (d, 1H, J = 8.8 Hz, ArH), 7.38-7.41(m, 1H, ArH),
7.33 (d, 2H, J = 8.0 Hz, ArH), 7.18 (d, 2H, J = 8.4 Hz , ArH),
5.83 (s, 1H, CH), 2.61-2.62 (m, 2H, CH2), 2.25-2.26 (m, 2H,
CH2), 1.77-1.95 (m, 2H, CH2). Anal. calcd for C22H17BrN2O: C,
65.20; H, 4.23; N, 6.91. Found C, 65.22; H, 4.25; N, 6.90.
9,10-Dihydro-12-(4-methoxyphenyl)benzo[b][4,7]phenan-
throlin-11(7H,8H,12H)-one (4d). This compound was obtained
as yellow solid (95% ethanol), mp>300 °C; ir (potassium
bromide): 3261, 3191, 3025, 1603, 1513, 1422, 1386, 1279,
1189, 1030, 962 cm-1; 1H nmr: δ 9.86 (s, 1H, NH), 8.66-8.67 (m,
1H, ArH), 8.34 (d, 1H, J = 8.4 Hz, ArH), 7.87 (d, 1H, J = 8.8
Hz, ArH), 7.54 (d, 1H, J = 9.2 Hz, ArH), 7.38-7.41 (m, 1H,
ArH), 7.12 (d, 2H, J = 8.0 Hz, ArH), 6.69 (d, 2H, J = 8.0 Hz,
ArH), 5.77 (s, 1H, CH), 3.61 (s, 3H, OCH3), 2.60-2.61 (m, 2H,
CH2), 2.23-2.24 (m, 2H, CH2), 1.91-1.96 (m, 2H, CH2). Anal.
calcd for C23H20N2O2: C, 77.51; H, 5.66; N, 7.86. Found C,
77.55; H, 5.64; N, 7.85.
9,10-Dihydro-12-phenylbenzo[b][4,7]phenanthrolin-11-
(7H,8H,12H)-one (4j). This compound was obtained as yellow
solid (95% ethanol), mp>300 °C; ir (potassium bromide): 3248,
3065, 3021, 1604, 1513, 1493, 1385, 1278, 1139, 1029, 961
12-(2,4-Dichlorophenyl)-9,10-dihydrobenzo[b][4,7]phen-
anthrolin-11(7H,8H,12H)-one (4e). This compound was
obtained as yellow solid (95% ethanol), mp>300 °C; ir
(potassium bromide): 3260, 3190, 3095, 1615, 1602, 1517,
1
cm-1; H nmr: δ 9.89 (s, 1H, NH), 8.66-8.67 (m, 1H, ArH), 8.35
(d, 1H, J = 8.8 Hz, ArH), 7.88 (d, 1H, J = 8.8 Hz, ArH), 7.56 (d,
1H, J = 8.8 Hz, ArH), 7.38-7.41 (m, 1H, ArH), 7.23 (d, 2H, J =
7.6Hz, ArH), 7.13 (t, 2H, J = 7.6 Hz, ArH), 7.00 (t, 1H, J = 7.2
Hz, ArH), 5.83 (s, 1H, CH), 2.61-2.64 (m, 2H, CH2), 2.25-2.26
(m, 2H, CH2), 1.77-1.96 (m, 2H, CH2). Anal. calcd for
C22H18N2O: C, 80.96; H, 5.56; N, 8.58. Found C, 80.95; H, 5.55;
N, 8.60.
1
1466, 1342, 1236, 1163, 1006, 958, 818 cm-1; H nmr: δ 10.03
(s, 1H, NH), 8.67-8.68 (m, 1H, ArH), 8.41 (d, 1H, J = 8.4 Hz,
ArH), 7.89 (d, 1H, J = 8.8 Hz, ArH), 7.53 (d, 1H, J = 8.8 Hz,
ArH), 7.44-7.47 (m, 1H, ArH), 7.40 (s, 1H, ArH), 7.34 (d, 1H, J
= 8.4 Hz, ArH), 7.23 (d, 1H, J = 8.8 Hz, ArH), 6.02 (s, 1H, CH),
2.63-2.64 (m, 2H, CH2), 2.20-2.27 (m, 2H, CH2), 1.77-1.94 (m,
2H, CH2). Anal. calcd for C22H16Cl2N2O: C, 66.85; H, 4.08; N,
7.09. Found C, 66.88; H, 4.05; N, 7.10.
9,10-Dihydro-12-(3,4-dimethoxyphenyl)benzo[b][4,7]phen-
anthrolin-11(7H,8H,12H)-one (4f). This compound was
obtained as yellow solid (95% ethanol), mp>300 °C; ir (potassium
bromide): 3259, 3195, 3100, 2950, 1605, 1516, 1464, 1337, 1236,
1138, 1023, 964, 808 cm-1; 1H nmr: δ 9.87 (s, 1H, NH), 8.66-8.67
(m, 1H, ArH), 8.39 (d, 1H, J = 8.8 Hz, ArH), 7.87 (d, 1H, J = 8.8
Hz, ArH), 7.54 (d, 1H, J = 8.8 Hz, ArH), 7.39-7.42 (m, 1H, ArH),
7.00 (s, 1H, ArH), 6.67 (d, 1H, J = 8.0 Hz, ArH), 6.51 (d, 1H, J =
8.4 Hz, ArH), 5.78 (s, 1H, CH), 3.65 (s, 3H, OCH3), 3.59 (s, 3H,
OCH3), 2.62 (s, 2H, CH2), 2.26 (s, 2H, CH2), 1.78-1.96 (m, 2H,
CH2). Anal. calcd for C24H22N2O3: C, 74.59; H, 5.74; N, 7.25.
Found C, 74.56; H, 5.75; N, 7.24.
9,10-Dihydro-12-(3-nitrophenyl)benzo[b][4,7]phenanthro-
lin-11(7H,8H,12H)-one (4g). This compound was obtained as
yellow solid (95% ethanol), mp>300 °C; ir (potassium bromide):
3273, 3193, 3098, 2941,1605, 1525, 1426, 1352, 1234, 1188,
1095, 963, 806 cm-1; 1H nmr: δ 10.07 (s, 1H, NH), 8.67-8.68 (m,
1H, ArH), 8.37 (d, 1H, J = 8.0 Hz, ArH), 8.09 (s, 1H, ArH),
7.90-7.95 (m, 2H, ArH), 7.59-7.66 (m, 2H, ArH), 7.39-7.48 (m,
2H, ArH), 6.02 (s, 1H, CH), 2.64 (s, 2H, CH2), 2.26-2.30 (m,
2H, CH2), 1.76-1.95 (m, 2H, CH2). Anal. calcd for C22H17N3O3:
C, 71.15; H, 4.61; N, 11.31. Found C, 71.16; H, 4.60; N, 11.30.
9,10-Dihydro-12-(4-hydroxy-3-nitrophenyl)benzo[b][4,7]-
phenanthrolin-11(7H,8H,12H)-one (4k). This compound was
obtained as yellow solid (95% ethanol), mp>300 °C; ir
(potassium bromide): 3250, 3183, 3062, 1602, 1515, 1463,
1
1387, 1280, 1189, 1038, 957 cm-1; H nmr: δ 10.63-10.64 (m,
1H, OH), 9.93 (s, 1H, NH), 8.68-8.69 (m, 1H, ArH), 8.35 (d,
1H, J = 8.4 Hz, ArH), 7.91 (d, 1H, J = 9.6 Hz, ArH), 7.71-7.72
(m, 1H, ArH), 7.57 (d, 1H, J = 8.4 Hz, ArH), 7.40-7.43 (m, 1H,
ArH), 7.36 (dd, 1H, J1 = 8.0 Hz, J2 = 1.6 Hz, ArH), 6.93 (d, 1H,
J = 8.4 Hz, ArH), 5.85 (s, 1H, CH), 2.62-2.64 (m, 2H, CH2),
2.27-2.34 (m, 2H, CH2), 1.82-1.99 (m, 2H, CH2). Anal. calcd for
C22H17N3O4: C, 68.21; H, 4.42; N, 10.85. Found C, 68.22; H,
4.45; N, 10.84.
9,10-Dihydro-12-(thiophen-2yl)benzo[b][4,7]phenanthrol-
in-11(7H,8H,12H)-one (4l). This compound was obtained as
yellow solid (95% ethanol), mp>300 °C; ir (potassium bromide):
3253, 3194, 3099, 2956, 1606, 1516, 1424, 1336, 1234, 1188,
1075, 961, 814 cm-1; 1H nmr: δ 10.01 (s, 1H, NH), 8.72-8.73 (m,
1H, ArH), 8.43 (d, 1H, J = 8.4 Hz, ArH), 7.91 (d, 1H, J = 8.8
Hz, ArH), 7.53 (d, 1H, J = 8.8 Hz, ArH), 7.46-7.49 (m, 1H,
ArH), 7.13-7.14 (m, 1H, ArH), 6.72-6.74 (m, 1H, ArH), 6.59-
6.60 (m, 1H, ArH), 6.14 (s, 1H, CH), 2.63-2.64 (m, 2H, CH2),
2.31-2.34 (m, 2H, CH2), 1.83-2.00 (m, 2H, CH2). Anal. calcd for
C20H16N2OS: C, 72.26; H, 4.85; N, 8.43; S, 9.65. Found C,
72.25; H, 4.86; N, 8.44; S, 9.70.

Mar-Apr 2008
An Efficient and Facile Microwave-assisted Synthesis of Benzo[b][4,7]phenanthroline
409
12-(4-Fluorophenyl)-9,10-dihydro-9,9-dimethylbenzo[b]-
[4,7]phenanthrolin-11(7H,8H,12H)-one (4m). This compound
was obtained as yellow solid (95% ethanol), mp>300 °C; ir
(potassium bromide): 3272, 3103, 3071, 1697, 1517, 1467,
Anal. calcd for C24H20Cl2N2O: C, 68.09; H, 4.76; N, 6.62. Found
C, 68.10; H, 4.75; N, 6.65.
9,10-Dihydro-12-(3,4-dimethoxyphenyl)-9,9-dimethylbenzo-
[b][4,7]phenanthrolin-11(7H,8H,12H)-one(4r). This com-
pound was obtained as yellow solid (95% ethanol), mp>300 °C;
ir (potassium bromide): 3259, 3190, 3098, 2955, 1607, 1515,
1
1385, 1290, 1182, 1094, 970 cm-1; H nmr: δ 9.86 (s, 1H, NH),
8.67-8.68 (m, 1H, ArH), 8.36 (d, 1H, J = 8.4 Hz, ArH), 7.89 (d,
1H, J = 8.8 Hz, ArH), 7.55 (d, 1H, J = 8.8 Hz, ArH), 7.39-7.42
(m, 1H, ArH), 7.24-7.28 (m, 2H, ArH), 6.96 (t, 2H, J = 8.8 Hz,
ArH), 5.82 (s, 1H, CH), 2.57 (d, 1H, J = 16.8 Hz, CH), 2.40 (d,
1H, J = 16.4 Hz, CH), 2.24 (d, 1H, J = 16.4 Hz, CH), 2.04 (d,
1H, J = 16.0 Hz, CH), 1.04 (s, 3H, CH3), 0.85 (s, 3H, CH3).
Anal. calcd for C24H21FN2O: C, 77.40; H, 5.68; N, 7.52. Found
C, 77.42; H, 5.66; N, 7.55.
1
1417, 1383, 1235, 1138, 1025, 980 cm-1; H nmr: δ 9.81 (s, 1H,
NH), 8.67-8.68 (m, 1H, ArH), 8.45 (d, 1H, J = 8.4 Hz, ArH),
7.87 (d, 1H, J = 9.2 Hz, ArH), 7.54 (d, 1H, J = 8.8 Hz, ArH),
7.40-7.43 (m, 1H, ArH), 6.98 (s, 1H, ArH), 6.68 (d, 1H, J = 8.4
Hz, ArH), 6.59 (d, 1H, J = 8.0 Hz, ArH), 5.74 (s, 1H, CH), 3.64
(s, 3H, OCH3), 3.60 (s, 3H, OCH3), 2.57 (d, 1H, J = 16.4 Hz,
CH), 2.41 (d, 1H, J = 16.8 Hz, CH), 2.24 (d, 1H, J = 16.4 Hz,
CH), 2.05 (d, 1H, J = 16.0 Hz, CH), 1.05 (s, 3H, CH3), 0.89 (s,
3H, CH3). Anal. calcd for C26H26N2O3: C, 75.34; H, 6.32; N,
6.76. Found C, 75.35; H, 6.33; N, 6.75.
9,10-Dihydro-9,9-dimethyl-12-(3-nitrophenyl)benzo[b]-
[4,7]phenanthrolin-11(7H,8H,12H)-one (4s). This compound
was obtained as yellow solid (95% ethanol), mp>300 °C; ir
(potassium bromide): 3268, 3194, 3086, 1601, 1522, 1468,
1392, 1299, 1153, 1030, 984 cm-1; 1H nmr: δ 10.01 (s, 1H, NH),
8.67-8.68 (m, 1H, ArH), 8.42 (d, 1H, J = 8.0 Hz, ArH), 8.12 (s,
1H, ArH), 7.92 (t, 2H, J = 9.6 Hz, ArH), 7.69 (d, 1H, J = 7.6 Hz,
ArH), 7.59 (d, 1H, J = 8.8 Hz, ArH), 7.46 (t, 1H, J = 8.0 Hz,
ArH), 7.39-7.42 (m, 1H, ArH), 5.99 (s, 1H, CH), 2.57 (d, 1H, J
= 16.4 Hz, CH), 2.41 (d, 1H, J = 16.8 Hz, CH), 2.24 (d, 1H, J =
16.4 Hz, CH), 2.05 (d, 1H, J = 16.0 Hz, CH), 1.04 (s, 3H, CH3),
0.82 (s, 3H, CH3). Anal. calcd for C24H21N3O3: C, 72.16; H, 5.30;
N, 10.52. Found C, 72.18; H, 5.32; N, 10.55.
12-(4-Chlorophenyl)-9,10-dihydro-9,9-dimethylbenzo[b]-
[4,7]phenanthrolin-11(7H,8H,12H)-one (4n). This compound
was obtained as yellow solid (95% ethanol), mp>300 °C; ir
(potassium bromide): 3262, 3106, 3024, 1601, 1516, 1464,
1
1384, 1258, 1159, 1093, 966 cm-1; H nmr: δ 9.89 (s, 1H, NH),
8.67-8.68 (m, 1H, ArH), 8.35 (d, 1H, J = 8.4 Hz, ArH), 7.90 (d,
1H, J = 9.2 Hz, ArH), 7.55 (d, 1H, J = 8.8 Hz, ArH), 7.39-7.42
(m, 1H, ArH), 7.20-7.27 (m, 4H, ArH), 5.81 (s, 1H, CH), 2.58
(d, 1H, J = 16.8 Hz, CH), 2.40 (d, 1H, J = 16.8 Hz, CH), 2.24 (d,
1H, J = 16.0 Hz, CH), 2.04 (d, 1H, J = 16.0 Hz, CH), 1.04 (s,
3H, CH3), 0.85 (s, 3H, CH3). Anal. calcd for C24H21ClN2O: C,
74.12; H, 5.44; N, 7.20. Found C, 74.15; H, 5.45; N, 7.25.
12-(4-Bromophenyl)-9,10-dihydro-9,9-dimethylbenzo[b]-
[4,7]phenanthrolin-11(7H,8H,12H)-one (4o). This com-
pound was obtained as yellow solid (95% ethanol), mp>300
°C; ir (potassium bromide): 3261, 3100, 3071, 1604, 1521,
1
1414, 1385, 1241, 1171, 1099, 966 cm-1; H nmr: δ 9.89 (s,
12-(Benzo[d][1,3]dioxo-5-yl)-9,10-dihydro-9,9-dimethyl-
benzo[b][4,7]phenanthrolin-11(7H,8H,12H)-one (4t). This
compound was obtained as yellow solid (95% ethanol), mp>300
°C; ir (potassium bromide): 3256, 3172, 3071, 1591, 1520, 1414,
1H, NH), 8.67-8.68 (m, 1H, ArH), 8.34 (d, 1H, J = 8.8 Hz,
ArH), 7.90 (d, 1H, J = 8.8 Hz, ArH), 7.55 (d, 1H, J = 8.8 Hz,
ArH), 7.39-7.42 (m, 1H, ArH), 7.19-7.35 (m, 4H, ArH), 5.80
(s, 1H, CH), 2.57 (d, 1H, J = 16.8 Hz, CH), 2.40 (d, 1H, J =
16.4 Hz, CH), 2.24 (d, 1H, J = 16.0 Hz, CH), 2.03 (d, 1H, J =
16.0 Hz, CH), 1.04 (s, 3H, CH3), 0.85 (s, 3H, CH3). Anal. calcd
for C24H21BrN2O: C, 66.52; H, 4.88; N, 6.46. Found C, 66.55;
H, 4.90; N, 6.45
1
1385, 1240, 1180, 1092, 965 cm-1; H nmr: δ 9.80 (s, 1H, NH),
8.67-8.68 (m, 1H, ArH), 8.39 (d, 1H, J = 8.4 Hz, ArH), 7.88 (d,
1H, J = 8.8 Hz, ArH), 7.54 (d, 1H, J = 8.8 Hz, ArH), 7.40-7.43
(m, 1H, ArH), 6.82 (s, 1H, ArH), 6.63-6.67 (m, 2H, ArH), 5.85-
5.88 (m, 2H, CH2), 5.74 (s, 1H, CH), 2.55 (d, 1H, J = 16.8 Hz,
CH), 2.42 (d, 1H, J = 16.4 Hz, CH), 2.23 (d, 1H, J = 16.0 Hz,
CH), 2.06 (d, 1H, J = 16.0 Hz, CH), 1.04 (s, 3H, CH3), 0.89 (s,
3H, CH3). Anal. calcd for C25H22N2O3: C, 75.36; H, 5.57; N,
7.03. Found C, 75.35; H, 5.58; N, 7.00.
9,10-dihydro-12-(4-methoxyphenyl)-9,9-dimethylbenzo[b]-
[4,7]phenanthrolin-11(7H,8H,12H)-one(4p). This com-pound
was obtained as yellow solid (95% ethanol), mp>300 °C; ir
(potassium bromide): 3258, 3098, 3070, 1602, 1520, 1422,
1
1391, 1239, 1173, 1029, 981 cm-1; H nmr: δ 9.77 (s, 1H, NH),
12-(2-Chlorophenyl)-9,10-dihydro-9,9-dimethylbenzo[b]-
[4,7]phenanthrolin-11(7H,8H,12H)-one (4u). This compound
was obtained as yellow solid (95% ethanol), mp>300 °C; ir
(potassium bromide): 3249, 3170, 3066, 1605, 1521, 1465,
8.66-8.67 (m, 1H, ArH), 8.36 (d, 1H, J = 8.4 Hz, ArH), 7.87 (d,
1H, J = 9.2 Hz, ArH), 7.53 (d, 1H, J = 9.2 Hz, ArH), 7.38-7.41
(m, 1H, ArH), 7.14 (d, 2H, J = 8.4 Hz, ArH), 6.69 (d, 2H, J = 8.4
Hz, ArH), 5.74 (s, 1H, CH), 3.61 (s, 3H, OCH3), 2.56 (d, 1H, J =
16.8 Hz, CH), 2.40 (d, 1H, J = 16.8 Hz, CH), 2.23 (d, 1H, J =
16.4 Hz, CH), 2.03 (d, 1H, J = 16.0 Hz, CH), 1.04 (s, 3H, CH3),
0.87 (s, 3H, CH3). Anal. calcd for C25H24N2O2: C, 78.10; H, 6.29;
N, 7.29. Found C, 78.11; H, 6.30; N, 7.30
1
1312, 1241, 1173, 1033, 979 cm-1; H nmr: δ 9.91 (s, 1H, NH),
8.66-8.67 (m, 1H, ArH), 8.50 (d, 1H, J = 8.4 Hz, ArH), 7.88 (d,
1H, J = 8.8 Hz, ArH), 7.53 (d, 1H, J = 8.8 Hz, ArH), 7.43-7.46
(m, 1H, ArH), 7.36 (d, 1H, J = 7.6 Hz, ArH), 7.25 (d, 1H, J = 8.0
Hz, ArH), 7.13 (t, 1H, J = 7.6 Hz, ArH), 7.02-7.05 (m, 1H,
ArH), 6.02 (s, 1H, CH), 2.61 (d, 1H, J = 16.4 Hz, CH), 2.42 (d,
1H, J = 16.4 Hz, CH), 2.23 (d, 1H, J = 16.0 Hz, CH), 2.00 (d,
1H, J = 16.0 Hz, CH), 1.05 (s, 3H, CH3), 0.88 (s, 3H, CH3).
Anal. calcd for C24H21ClN2O: C, 74.12; H, 5.44; N, 7.20. Found
C, 74.13; H, 5.43; N, 7.25.
12-(2,4-Dichlorophenyl)-9,10-dihydro-9,9-dimethylbenzo-
[b][4,7]phenanthrolin-11(7H,8H,12H)-one (4q). This compound
was obtained as yellow solid (95% ethanol), mp>300 °C; ir
(potassium bromide): 3255, 3177, 3066, 2954, 1605, 1522,
1
1420, 1394, 1241, 1147, 1032, 983 cm-1; H nmr: δ 9.98 (s, 1H,
NH), 8.67-8.68 (m, 1H, ArH), 8.41 (d, 1H, J = 8.4 Hz, ArH),
7.89 (d, 1H, J = 8.8 Hz, ArH), 7.52 (d, 1H, J = 8.8 Hz, ArH),
7.43-7.47 (m, 1H, ArH), 7.36-7.41 (m, 2H, ArH), 7.23-7.25 (m,
1H, ArH), 6.00 (s, 1H, CH), 2.61 (d, 1H, J = 16.8 Hz, CH), 2.41
(d, 1H, J = 16.8 Hz, CH), 2.23 (d, 1H, J = 16.0 Hz, CH), 2.00 (d,
1H, J = 16.0 Hz, CH), 1.05 (s, 3H, CH3), 0.88 (s, 3H, CH3).
9,10-Dihydro-9,9-dimethyl-12-phenylbenzo[b][4,7]phen-
anthrolin-11(7H,8H,12H)-one (4v). This compound was
obtained as yellow solid (95% ethanol), mp>300 °C; ir
(potassium bromide): 3253, 3170, 3070, 1602, 1592, 1423,
1
1333, 1236, 1161, 1068, 980 cm-1; H nmr: δ 9.84 (s, 1H, NH),
8.66-8.67 (m, 1H, ArH), 8.39 (d, 1H, J = 8.8 Hz, ArH), 7.88 (d,

410
F. Shi, D. Zhou, C. Li, Q. Shao, L. Cao, S. Tu
Vol 45
[4] (a) Loh, T.-P.; Wei, L.-L. Tetrahedron Lett. 1998, 39, 323;
(b) Azizi, N.; Torkiyan, L.; Saidi, M. R. Org. Lett. 2006, 8, 2079.
[5] (a) Liao, M.-C.; Duan, X.-H.; Liang, Y.-M. Tetrahedron Lett.
2005, 46, 3469; (b) Kinoshita, H.; Shinokubo, H.; Oshima, K. Org. Lett.
2004, 6, 4085; (c) Uozumi, Y.; Watanabe, T. J. Org. Chem. 1999, 64,
6921.
[6] (a) Zha, Z.; Hui, A.; Zhou, Y.; Miao, Q.; Wang, Z.; Zhang,
H. Org. Lett. 2005, 7, 1903; (b) Zha, Z.; Qiao, S.; Jiang, J.; Wang, Y.;
Miao, Q.; Wang, Z. Tetrahedron 2005, 61, 2521.
[7] (a) Botella, L.; Najera, C. J. Org. Chem. 2005, 70, 4360; (b)
Bhattacharya, S.; Srivastava, A.; Sengupta, S. Tetrahedron Lett. 2005,
46, 3557.
[8] (a) Fringuelli, F.; Piermatti, O.; Pizzo, F. Organic Synthesis
in Water, Grieco, P. A., Ed.; Blackie Academic & Professional; London,
1998; (b) Kobayashi, S. Organic Synthesis in Water, Grieco, P. A., Ed.;
Blackie Academic & Professional; London, 1998.
[9] Tu, S. J.; Jia, R. H.; Jiang, B.; Zhang, J. Y. ; Zhang, Y.; Yao,
C. S. ; Ji, S. J. Tetrahedron 2007, 63, 381.
[10] (a) Breslow, R.; Maitra, U.; Rideout, D. C. Tetrahedron Lett.
1983, 24, 1902; (b) Tan, X. H.; Hou, Y. Q.; Huang, C.; Liu, L.; Guo, Q.
X. Tetrahedron 2004, 60, 6129.
[11] (a) Copley, S. D.; Knowles, J. R. J. Am. Chem. Soc. 1987,
109, 5008; (b) Khosropour, A. R.; Khodaei, M. M.; Kookhazadeh, M.
Tetrahedron Lett. 2004, 45, 1725.
[12] (a) Bai, L.; Wang, J. -X.; Zhang, Y. Green Chem. 2003, 5,
615; (b) Leadbeater, N. E.; Marco, M. J. Org. Chem. 2003, 68, 888; (c)
Pironti, V.; Colonna, S. Green Chem. 2005, 7, 43.
1H, J = 8.8 Hz, ArH), 7.55 (d, 1H, J = 8.8 Hz, ArH), 7.39-7.42
(m, 1H, ArH), 7.25 (d, 2H, J = 7.6 Hz, ArH), 7.13 (t, 2H, J = 7.6
Hz, ArH), 7.00 (t, 1H, J = 7.6 Hz, ArH), 5.79 (s, 1H, CH), 2.57
(d, 1H, J = 16.8 Hz, CH), 2.41 (d, 1H, J = 16.8 Hz, CH), 2.23 (d,
1H, J = 16.0 Hz, CH), 2.03 (d, 1H, J = 16.0 Hz, CH), 1.04 (s,
3H, CH3), 0.85 (s, 3H, CH3). Anal. calcd for C24H22N2O: C,
81.33; H, 6.26; N,7.90. Found C, 81.35; H, 6.25; N, 7.92.
9,10-Dihydro-12-(4-hydroxy-3-nitrophenyl)-9,9-dimethyl-
benzo[b][4,7]phenanthrolin-11(7H,8H,12H)-one (4w). This
compound was obtained as yellow solid (95% ethanol), mp>300
°C; ir (potassium bromide): 3398, 3256, 3096, 2925, 1602, 1518,
1427, 1313, 1264, 1164, 1080, 982 cm-1; 1H nmr: δ 10.69 (s, 1H,
OH), 9.91 (s, 1H, NH), 8.69 (s, 1H, ArH), 8.39 (d, 1H, J = 8.8
Hz, ArH), 7.91 (d, 1H, J = 8.8 Hz, ArH), 7.75 (s, 1H, ArH), 7.55
(d, 1H, J = 9.2 Hz, ArH), 7.38-7.43 (m, 2H, ArH), 6.93 (d, 1H, J
= 8.8 Hz, ArH), 5.82 (s, 1H, CH), 2.57 (d, 1H, J = 16.8 Hz, CH),
2.42 (d, 1H, J = 16.4 Hz, CH), 2.25 (d, 1H, J = 16.0 Hz, CH),
2.05 (d, 1H, J = 16.0 Hz, CH), 1.04 (s, 3H, CH3), 0.86 (s, 3H,
CH3). Anal. calcd for C24H21N3O4: C, 69.39; H, 5.10; N, 10.11.
Found C, 69.40; H, 5.13; N, 10.10.
9,10-Dihydro-9,9-dimethyl-12-(thiophen-2-yl)benzo[b][4,7]-
phenanthrolin11(7H,8H,12H)-one (4x). This compound was
obtained as yellow solid (95% ethanol), mp>300 °C; ir
(potassium bromide): 3273, 3199, 3109, 1615, 1592, 1463,
1
1304, 1237, 1163, 1032, 981 cm-1; H nmr: δ 9.96 (s, 1H, NH),
[13] (a) Lidstrom, P.; Tierney, J.; Wathey, B.; Westman, J.
Tetrahedron 2001, 57, 9225; (b) Wu, X.; Larhed, M. Org. Lett. 2005, 7,
3327; (c) Wu, X.; Ekegren, J. K.; Larhed, M. Organometallics 2006, 25,
1434; (c) Gellis, A.; Boufatah, N.; Vanelle, P. Green Chem. 2006, 8, 483.
[14] Hofmann, A. in “Die Mutterkomalkaloide”, Ferdinand Enke
Verlag, Stuttgart, Germany, 1964.
[15] Cassady, J. M. and Floss, H. G. Lloydia, 1977, 40, 90.
[16] Jastrzebska-Glapa, M., Mlochowski, J. and Sliwa, W., Pol. J.
Chem. 1979, 53, 811.
8.71-8.72(m, 1H, ArH), 8.44 (d, 1H, J = 8.4 Hz, ArH), 7.91 (d,
1H, J = 8.8 Hz, ArH), 7.53 (d, 1H, J = 9.2 Hz, ArH), 7.46-7.49
(m, 1H, ArH), 7.13-7.14 (m, 1H, ArH), 6.72-6.74 (m, 1H, ArH),
6.63-6.64 (m, 1H, ArH), 6.13 (s, 1H, CH), 2.58 (d, 1H, J = 16.4
Hz, CH), 2.42 (d, 1H, J = 17.2 Hz, CH), 2.28 (d, 1H, J = 16.0
Hz, CH), 2.12 (d, 1H, J = 16.0 Hz, CH), 1.06 (s, 3H, CH3), 0.85
(s, 3H, CH3). Anal. calcd for C22H20N2OS: C, 73.30; H, 5.59; N,
7.77; S, 8.90. Found C, 73.33; H, 5.60; N, 7.75; S, 8.83.
[17] (a) Gusak, K. N., Tereshko, A. B. and Kozlov, N. G. Russ. J.
Org. Chem. 2001, 37, 1495 ; (b) Gusak, K. N., Kozlov, N. G. and
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.
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).
[18] The single-crystal growth was carried out in ethanol at room
temperature. X-ray crystallographic analysis was performed with
a
REFERENCES AND NOTES
Siemens SMART CCD and Semens P4 diffractometer (graphite
a
monochromator, MoKa radiation λ = 0.71073 Å). Crystal data for:
Empirical formula C23H20N2O2, yellow, crystal dimension 0.25×0.22×0.17
mm, monoclinic, space group C2/c, a = 25.072(3) Å, b = 7.3183(16) Å, c =
23.335(2) Å, α = 90°, β = 107.922(2)°, γ = 90°, V = 4073.9(11) Å3, Mr =
356.41, Z = 8, Dc = 1.162 Mg/m3, λ = 0.71073 Å, µ (MoKα) = 0.075
mm-1, F(000) = 1504, S = 1.016, R1 = 0.074, wR2 = 0.114
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