Synthesis and antimicrobial activity of some 7-aryl-5,6-dihydro-14-aza[1] benzopyrano[3,4-b]phenanthren-8H-ones

Article abstract of DOI:10.1002/jhet.648

Figure represented. The title compounds, 7-aryl-5,6-dihydro-14-aza[1] benzopyrano[3,4-b]phenanthren-8H-ones 3a-l have been synthesized by reacting various 4-hydroxy coumarins 1a-c with 2-arylidene-1-tetralones 2a-d in the presence of ammonium acetate and

Full text of DOI:10.1002/jhet.648

840
Synthesis and Antimicrobial Activity of Some 7-Aryl-5,6-
dihydro-14-aza[1]benzopyrano[3,4-b]phenanthren-8H-ones
Vol 48
Dinker I. Brahmbhatt,* Niraj H. Patel, Anil K. Patel,
Mehul A. Patel, and Varun G. Patel
Department Of Chemistry, Sardar Patel University, Vallabh Vidyanagar-388 120, Gujarat, India
*E-mail: drdibrahmbhatt@gmail.com
Received March 25, 2010
DOI 10.1002/jhet.648
Published online 12 April 2011 in Wiley Online Library (wileyonlinelibrary.com).
The title compounds, 7-aryl-5,6-dihydro-14-aza[1]benzopyrano[3,4-b]phenanthren-8H-ones 3a-l have
been synthesized by reacting various 4-hydroxy coumarins 1a-c with 2-arylidene-1-tetralones 2a-d in
the presence of ammonium acetate and acetic acid under Krohnke’s reaction condition. The structures
1
of all the synthesized compounds were supported by analytical, IR, H-NMR, and 13C-NMR data. All
the synthesized compounds 3a-l have been screened for their antibacterial activities against Escherichia
coli (Gram ꢀve bacteria), Bacillus subtilis (Gram þve bacteria), and antifungal activity against Candida
albicans (Fungi).
J. Heterocyclic Chem., 48, 840 (2011).
INTRODUCTION
[14], where as 1-chloro-2-azaphenanthrene is found to
be a novel activator of cystic fibrosis transmembrane
Coumarins are a class of compounds having aromatic
d-lactones system, isolated from variety of plant sources
[1]. Coumarin derivatives are reported to have variety of
biological activities such as anti-inflammatory [2], anti-
viral [3], antioxidant [4], antibacterial [5], antifungal
[6], anti-HIV [7], and as anticarcinogenic material [8].
Coumarins fused with pyridine nucleus have been
reported to possess antiallergic [9], antidiabetic activities
[10] and even analgesic properties [11], being character-
ized by a phenanthrene-like structure as found in tetra-
hydrocannabinol. In view of such important bioactivity
of pyrido fused coumarins, earlier we had synthesized
some diarylpyrido[3,2-c]coumarins by the reaction of 4-
hydroxy coumarins with a,b-unsaturated ketones using
Krohnke’s reaction [12].
conductance regulator [15].
A 3-(4-methylsufonyl-
phenyl)-4-azaphenanthren-1-carboxylic acid acts as
cyclooxygenase-2 inhibitors [16]. These interesting bio-
logical properties of azaphenanthrene derivatives
prompted us to incorporate such type of nucleus in cou-
marin and therefore in this work we have synthesized
some 7-aryl-5,6-dihydro-14-aza[1]benzopyrano[3,4-b]
phenanthren-8H-ones.
The compounds 3a-l have been synthesized by react-
ing various 4-hydroxy coumarins 1a-c with 2-arylidene-
1-tetralones 2a-d in the presence of ammonium acetate
and acetic acid under Krohnke’s reaction condition. The
synthetic methodology is outline in Scheme 1.
RESULT AND DISCUSSION
Phenanthrene containing one nitrogen atom is known
as azaphenanthrene. During our literature search for aza-
phenanthrene, we came across some azaphenanthrene
derivatives having interesting biological activities. 4-
Azaphenanthrene derivatives have been reported to
possess wound healing, antibacterial and in vitro antiox-
idant activity [13]. The 1,3-diamino substituted 4-aza-
phenanthrene derivative possesses cytotoxic activity
The condensation of 4-hydroxy coumarins 1a-c with
2-arylidene-1-tetralones 2a-d under Krohnke’s reaction
condition proceeded smoothly and gave the expected 7-
aryl-5,6-dihydro-14-aza[1]benzopyrano[3,4-b]phenanth-
ren-8H-ones 3a-l in moderate yield (47–60%). A plau-
sible reaction mechanism for the formation of the com-
pounds 3a-l is depicted in Scheme 2.
C
V
2011 HeteroCorporation

July 2011
Synthesis and Antimicrobial Activity of Some 7-Aryl-5,6-dihydro-
14-aza[1]benzopyrano[3,4-b]phenanthren-8H-ones
841
Scheme 1. The synthetic scheme for the preparation of compounds 3a-l.
The structures of all the synthesized compounds 3a-l
activity towards E coli and B subtilis at all concentra-
tions. However though majority of the compounds
showed moderate activity against fungi C albicans, the
compound 3e showed poor activity and compound 3b
did not show activity at all. Here also the compounds
having chlorine substitution in coumarin moiety 3i-l
showed better activity compared with other compounds.
The comparison of the antimicrobial activity at different
concentrations indicates that the activity decreases with
decrease in concentration. All the synthesized com-
pounds show lower activity compared to standard drugs
at all the concentrations.
were established on the basis of analytical and spectral data.
In IR spectra, compounds 3a-l showed a very strong
band between 1715–1740 cmꢀ1 for the carbonyl (C¼¼O)
stretching of d-lactone ring present in coumarin nucleus.
The strong bands for aromatic C¼¼C and C¼¼N stretch-
ing vibrations, were observed between 1595–1630 cmꢀ1
and 1495–1520 cmꢀ1, respectively. The aliphatic and ar-
omatic CAH stretching vibrations were observed
between 2940–2980 cmꢀ1 and 3040–3065 cmꢀ1, respec-
tively in the form of medium bands.
1
In the H-NMR spectra of compounds 3a-l, two trip-
lets were observed between 2.69–2.75 d and 2.87–2.91
d each integrating for two protons. These signals are
due to protons attached at C6 and C5, respectively. In all
the compounds the signal for C1AH appeared either as
doublet of doublet or poorly resolved doublet of doublet
between 8.63–8.69 d. The C13AH appeared as a doublet
of a doublet between 8.84–8.86 d in compounds 3a-d,
while it appeared as a doublet or a poorly resolved dou-
blet between 8.60–8.78 d in compounds 3e-l. In all the
compounds, the other aromatic protons appeared as mul-
tiplet between 7.02–7.59 d. The C1AH and C13AH sig-
nals appear in the downfield region compared with other
aromatic protons due to peri effect of the nitrogen atom
present in the compound.
Scheme 2. The plausible mechanism for the formation of the com-
pounds 3a-l.
The 13C-NMR spectra of compounds 3a-l showed sig-
nals at around 25.0 and 28.0 d, which were due to C6
and C5, respectively. This was confirmed by DEPT-135
spectra in which these signals got inverted. The aro-
matic carbons including carbonyl carbon appeared
between 114.0–161.0 d.
For selected compound 3a, mass spectrum was
recorded. The mass spectrum of compound 3a showed
molecular ion peak at m/z 375 along with other fragments
peaks. This confirms the structure of compound 3a.
The results of the antimicrobial screening of the com-
pounds (Table 1) indicate that all the compounds 3a-l
show comparable activity against E coli and B subtilis.
Compared to compounds 3a-h, the compounds having
chlorine substitution in coumarin moiety 3i-l show better
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

842
D. I. Brahmbhatt, N. H. Patel, A. K. Patel, M. A. Patel, and V. G. Patel
Vol 48
Table 1
Antimicrobial activity of compounds 3a-l.
Inhibition zone in mm (1000 ppm
concentration)
Inhibition zone in mm (750 ppm
concentration)
Inhibition zone in mm (500 ppm
concentration)
Fungi
Bacteria
B subtilis
Fungi
Bacteria
B subtilis
Fungi
Bacteria
Compd.
E coli
C albicans
E coli
C albicans
E coli
B subtilis
C albicans
3a
3b
3c
3d
3e
3f
3g
3h
3i
15
16
17
15
17
15
15
14
16
16
17
17
18
20
–
17
19
19
20
16
18
17
20
18
18
19
20
25
27
–
15
–
12
16
6
13
10
12
14
17
18
14
–
14
14
15
15
14
11
12
12
16
15
17
17
18
20
–
15
17
16
19
15
16
14
19
17
16
17
20
25
27
–
13
–
12
15
5
11
10
11
13
12
10
09
11
14
15
14
15
18
20
–
12
13
11
17
13
11
12
17
15
14
16
17
25
27
–
11
–
08
12
5
10
07
07
11
12
10
11
–
11
9
11
13
15
15
12
–
3j
3k
3l
Ciprofloxacin
Ampicillin
Clotrimazole
–
20
–
20
–
20
EXPERIMENTAL
(CDCl3): d 2.71 (2H, t, protons at C6), 2.89 (2H, t, protons at
C5), 7.21–7.59 (11H, m, aromatic protons), 8.69 (1H, dd, J ¼ 7.2
and 1.2 Hz, C1AH), 8.86 (1H, dd, J ¼ 7.6 and 1.2 Hz, C13AH);
13C-NMR (CDCl3): 25.40(CH2), 27.64(CH2), 113.88(C),
116.70(CH), 119.94(C), 124.31(CH), 125.14(CH), 126.92(CH),
All the melting points reported are uncorrected. The IR
spectra (KBr disc) were recorded on Shimadzu FT-IR 8400-S
spectrometer. 1H-NMR and 13C-NMR spectra were recorded
on a Bruker Avance 400 spectrophotometer operating at 400
127.19(CH),
127.36(CH),
127.72(CH),
127.89(CH),
MHz for H-NMR and 100 MHz for 13C-NMR. The chemical
1
128.47(CH), 131.04(CH), 131.62(CH), 131.87(C), 133.85(C),
138.17(C), 139.42(C), 150.62(C), 152.10(C), 152.67(C),
157.27(C), 159.54(C¼¼O). Anal. Calcd. for C26H17NO2: C,
83.18; H, 4.56; N, 3.73. Found: C, 83.02; H, 4.50; N, 3.70.
7-(4-Methylphenyl)-5,6-dihydro-14-aza[1]benzopyrano[3,4-b]
phenanthren-8H-one (3b). White solid; Yield 55%; M.P. 259–
shift (d) is reported in ppm using chloroform-d as a solvent
and calibrated standard solvent signal. Mass spectrum for com-
pound 3a was recorded on Shimadzu QP 2010 spectrometer.
4-Hydroxy coumarins 1a-c and 2-arylidene-1-tetralones 2a-d
were prepared according to literature procedures [17,18].
General procedure for the synthesis of 7-aryl-5,6-dihy-
dro-14-aza[1]benzopyrano [3,4-b]phenanthren-8H-ones
(3a-l). In a 100 mL round-bottom flask equipped with a drop-
ping funnel, condenser, guard tube, and magnetic needle, an
appropriate 4-hydroxy coumarin (1a-c) (0.004 mol) was taken in
glacial acetic acid (15 mL). To this, ammonium acetate (0.04
mol) was added with stirring at room temperature. Then a solu-
tion of appropriate 2-arylidene-1-tetralone (2a-d) (0.004 mol) in
acetic acid (15 mL) was added with stirring at room temperature.
The reaction mixture was further stirred for 45 min. and then
refluxed in an oil bath at 140-150ꢁC for 8 h and cooled to room
temperature. The reaction mixture was poured into ice cold
water (75 mL) and the gummy mass obtained was extracted with
chloroform (3 ꢂ 30 mL). The combined chloroform extract was
washed with 10% sodium bicarbonate solution (3 ꢂ 20 mL) and
then with water (3 ꢂ 20 mL). It was dried over anhydrous so-
dium sulfate. The removal of chloroform under vacuum gave a
solid product. This was purified by column chromatography
using silica gel and chloroform-petroleum ether (60–80) (4:6) as
an eluent. Thus 7-aryl-5,6-dihydro-14-aza[1]benzo pyrano[3,4-
b]phenanthren-8H-ones (3a-l) were obtained as a solid material,
which were recrystallized from chloroform-hexane.
1
260ꢁC; IR (KBr, cmꢀ1): 3040, 2960, 1715, 1600, 1500, 830; H-
NMR (CDCl3): d 2.50 (3H, s, CH3), 2.71 (2H, t, protons at C6),
2.87 (2H, t, protons at C5), 7.10–7.58 (10H, m, aromatic protons),
8.67 (1H, dd, J ¼ 7.2 and 1.2 Hz, C1AH), 8.84 (1H, dd, J ¼ 7.6
and 1.2 Hz, C13AH); 13C-NMR (CDCl3): 21.51(CH3), 25.42(CH2),
27.66(CH2), 114.03(C), 116.67(CH), 119.98(C), 124.27(CH),
125.14(CH), 126.90(CH), 127.11(CH), 127.33(CH), 127.86(CH),
129.21(CH), 130.97(CH), 131.56(CH), 132.04(C), 133.91(C),
135.12(C), 137.35(C), 139.43(C), 150.58(C), 152.32(C), 152.66(C),
157.15(C), 159.55(C¼¼O). Anal. Calcd. for C27H19NO2: C, 83.27;
H, 4.92; N, 3.60. Found: C, 83.14; H, 4.85; N, 3.55.
7-(4-Methoxyphenyl)-5,6-dihydro-14-aza[1]benzopyrano[3,4-b]
phenanthren-8H-one (3c). White solid; Yield 54%, M.P. 212–
214ꢁC; IR (KBr, cmꢀ1): 3055, 2940, 1730, 1605, 1510, 830;
1H-NMR (CDCl3): d 2.73 (2H, t, protons at C6), 2.88 (2H, t,
protons at C5), 3.92 (3H, s, OCH3), 7.05-7.58 (10H, m, aro-
matic protons), 8.67 (1H, poorly resolved dd, C1AH), 8.84
(1H, dd, J ¼ 8.0 and 1.6 Hz, C13AH); 13C-NMR (CDCl3):
25.45(CH2), 27.69(CH2), 55.26(OCH3), 113.92(CH), 114.15(C),
116.66(CH), 119.99(C), 124.28(CH), 125.15(CH), 126.90(CH),
127.34(CH), 127.86(CH), 128.55(CH), 130.14(C), 130.98(CH),
131.57(CH), 132.31(C), 133.93(C), 139.42(C), 150.62(C),
152.05(C), 152.65(C), 157.18(C), 159.10(C), 159.62(C¼¼O).
Anal. Calcd. for C27H19NO3: C, 79.98; H, 4.72; N, 3.45.
Found: C, 79.89; H, 4.68; N, 3.42.
7-Phenyl-5,6-dihydro-14-aza[1]benzopyrano[3,4-b]phenanth-
ren-8H-one (3a). White solid; Yield 59%; M.P. 255ꢁC; IR
(KBr, cmꢀ1): 3065, 2945, 1734, 1595, 1495, 765, 700 H-NMR
1
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

July 2011
Synthesis and Antimicrobial Activity of Some 7-Aryl-5,6-dihydro-
14-aza[1]benzopyrano[3,4-b]phenanthren-8H-ones
843
7.02–7.54 (9H, m, aromatic protons), 8.62 (1H, d, J ¼ 1.6 Hz,
C13AH), 8.69 (1H, dd, J ¼ 7.6 and 1.2 Hz, C1AH); 13C-NMR
(CDCl3): 21.17(CH3), 25.29(CH2), 27.63(CH2), 118.14(CH),
119.03(C), 121.49(C), 124.61(CH), 126.92(CH), 127.37(CH),
127.84(CH), 128.91(CH), 129.74(C), 131.00(CH), 131.28(CH),
133.53(C), 133.85(C), 139.54(C), 149.15(C), 149.39(C),
150.96(C), 157.10(C), 157.34(C), 158.97(C), 161.05(C¼¼O).
Anal. Calcd. for C27H18ClNO2: C, 76.50; H, 4.28; N, 3.30.
Found: C, 76.38; H, 4.22; N, 3.27.
12-Chloro-7-phenyl-5,6-dihydro-14-aza[1]benzopyrano[3,4-b]
phenanthren-8H-one (3i). Yellow solid; Yield 51%; M.P.
184ꢁC; IR(KBr, cmꢀ1): 3055, 2980, 1740, 1605, 1520, 700,
745; 1H-NMR (CDCl3): d 2.73 (2H, t, protons at C6), 2.91
(2H, t, protons at C5), 7.22–7.56 (10H, m, aromatic protons),
8.68–8.80 (2H, m, C1AH and C13AH merged); 13C-NMR
(CDCl3): 25.50(CH2), 27.58(CH2), 113.94(C), 118.28(CH),
121.28(C), 124.71(CH), 126.98(CH), 127.15(CH), 127.52(CH),
7-(4-Chlorophenyl)-5,6-dihydro-14-aza[1]benzopyrano[3,4-b]
phenanthren-8H-one (3d). White solid; Yield 48%; M.P.
284ꢁC; IR (KBr, cmꢀ1): 3060, 2960, 1735, 1600, 1495, 830; 1H-
NMR (CDCl3): d 2.69 (2H, t, protons at C6), 2.89 (2H, t, protons
at C5), 7.14–7.59 (10H, m, aromatic protons), 8.67 (1H, dd, J ¼
6.8 and 1.6 Hz, C1AH), 8.84 (1H, dd, J ¼ 8.0 and 1.6 Hz,
C13AH); 13C-NMR (CDCl3): 25.42(CH2), 27.55(CH2),
113.72(C), 116.72(CH), 119.81(C), 124.43(CH), 125.15(CH),
126.96(CH), 127.43(CH), 127.92(CH), 128.70(CH), 128.82(CH),
131.19(CH), 131.77(CH), 131.80(C), 133.70(C), 133.76(C),
136.53(C), 139.35(C), 150.72(C), 150.79(C), 152.62(C),
157.45(C), 159.59(C¼¼O). Anal. Calcd. for C26H16ClNO2: C,
76.19; H, 3.93; N, 3.42. Found: C, 76.31; H, 3.91; N, 3.39.
12-Methyl-7-phenyl-5,6-dihydro-14-aza[1]benzopyrano[3,4-b]
phenanthren-8H-one (3e). Light yellow solid; Yield 52%; M.P.
205ꢁC; IR(KBr, cmꢀ1): 3060, 2960, 1720, 1605, 1500, 710, 750;
1H-NMR (CDCl3): d 2.55 (3H, s, CH3), 2.70 (2H, t, protons at
C6), 2.88 (2H, t, protons at C5), 7.21–7.55 (10H, m, aromatic pro-
tons), 8.61 (1H, d, J ¼ 1.2 Hz, C13AH), 8.69 (1H, dd, J ¼ 7.2 and
0.8 Hz, C1AH); 13C-NMR (CDCl3): 21.16(CH3), 25.41(CH2),
27.66(CH2), 113.89(C), 116.47(CH), 119.50(C), 124.80(CH),
126.91(CH), 127.18(CH), 127.36(CH), 127.67(CH), 127.88(CH),
128.45(CH), 130.99(CH), 131.73(C), 132.61(CH), 133.93(C),
138.26(C), 139.42(C), 150.69(C), 150.79(C), 152.12(C),
157.17(C), 159.70(C¼¼O). Anal. Calcd. for C27H19NO2: 83.27; H,
4.92; N, 3.60. Found: C, 83.36; H, 4.90; N, 3.52.
127.89(CH),
128.56(CH),
129.90(CH),
131.31(CH),
131.62(CH), 132.59(C), 133.63(C), 137.85(C), 139.38(C),
149.54(C), 150.70(C), 151.07(C), 152.23(C), 157.55(C),
159.02(C¼¼O). Anal. Calcd. for C26H16ClNO2: C, 76.19; H,
3.93; N, 3.44. Found: C, 76.25; H, 3.97; N, 3.44.
12-Chloro-7-(4-methylphenyl)-5,6-dihydro-14-aza[1]benzo-
pyrano[3,4-b]phenanthren-8H-one (3j). Light yellow solid;
Yield 48%; M.P. 260–262ꢁC; IR(KBr, cmꢀ1): 3040, 2960,
1
1740, 1600, 1515, 825; H-NMR (CDCl3): d 2.49 (3H, singlet,
CH3), 2.72 (2H, t, protons at C6), 2.88 (2H, t, protons at C5),
7.08–7.51 (9H, m, aromatic protons), 8.66 (1H, poorly
resolved dd, C1AH), 8.78 (1H, poorly resolved d, C13AH);
13C-NMR (CDCl3): 21.69(CH3), 25.61(CH2), 27.70(CH2),
114.08(C), 118.23(CH), 121.25(C), 124.66(CH), 127.07(CH),
127.45(CH), 127.89(CH), 129.27(CH), 129.86(C), 131.24(CH),
131.53(CH), 132.78(C), 133.65(C), 134.79(C), 137.52(C),
139.47(C), 149.49(C), 151.06(C), 152.47(C), 157.42(C),
159.03(C¼¼O). Anal. Calcd. for C27H18ClNO2: C, 76.50; H,
4.28; N, 3.30. Found: C, 76.38; H, 4.23; N, 3.36.
12-Methyl-7-(4-methylphenyl)-5,6-dihydro-14-aza[1]benzo-
pyrano[3,4-b]phenanthren-8H-one (3f). Light yellow solid;
Yield 54%; M.P. 220–222ꢁC; IR(KBr, cmꢀ1): 3060, 2960,
1730, 1610, 1510, 825; 1H-NMR (CDCl3): d 2.49 and 2.55
(6H, two singlets, 2 ꢂ CH3), 2.71 (2H, t, protons at C6), 2.87
(2H, t, protons at C5), 7.09–7.52 (9H, m, aromatic protons),
8.60 (1H, poorly resolved d, C13AH), 8.68 (1H, poorly
resolved dd, C1AH); 13C-NMR (CDCl3): 21.16(CH3),
21.50(CH3), 25.42(CH2), 27.68(CH2), 114.04(C), 116.44(CH),
119.54(C), 124.80(CH), 126.90(CH), 127.11(CH), 127.33(CH),
127.85(CH), 129.19(CH), 130.93(CH), 131.89(C), 132.55(CH),
133.87(C), 133.97(C), 135.22(C), 137.28(C), 139.42(C),
150.66(C), 150.78(C), 152.34(C), 157.05(C), 159.70(C¼¼O).
Anal. Calcd. for C28H21NO2: C, 83.35; H, 5.25; N, 3.47.
Found: C, 83.26; H, 5.19; N, 3.49.
12-Chloro-7-(4-methoxyphenyl)-5,6-dihydro-14-aza[1]ben-
zopyrano[3,4-b]phenanthren-8H-one
(3k). Light
yellow
solid; Yield 55%; M.P. 194–196ꢁC; IR(KBr, cmꢀ1): 3055,
2980, 1725, 1615, 1510, 810; 1H-NMR (CDCl3): d 2.74 (2H,
t, protons at C6), 2.88 (2H, t, protons at C5), 3.91 (3H, s,
OCH3), 7.04–7.50 (9H, m, aromatic protons), 8.65 (1H, poorly
resolved dd, C1AH), 8.76 (1H, d, J ¼ 1.2 Hz, C13AH); 13C-
NMR (CDCl3): 25.51(CH2), 27.60(CH2), 55.26(OCH3),
113.97(CH), 114.20(C), 118.19(CH), 121.29(C), 124.68(CH),
127.01(CH), 127.45(CH), 127.89(CH), 128.52(CH), 129.86(C),
131.21(CH), 131.50(CH), 133.03(C), 133.66(C), 139.41(C),
149.51(C), 151.03(C), 152.19(C), 157.44(C), 159.21(C¼¼O).
Anal. Calcd. for C27H18ClNO3: C, 73.72; H, 4.12; N, 3.18.
Found: C, 73.59; H, 4.18; N, 3.17.
12-Methyl-7-(4-methoxyphenyl)-5,6-dihydro-14-aza[1]benzo-
pyrano[3,4-b]phenanthren-8H-one (3g). White solid; Yield
60%; M.P. 161–162ꢁC; IR(KBr, cmꢀ1): 3040, 2970, 1735,
1
1610, 1505, 835; H-NMR (CDCl3): d 2.55 (3H, s, CH3), 2.73
(2H, t, protons at C6), 2.88 (2H, t, protons at C5), 3.91 (3H, s,
OCH3), 7.04–7.53 (9H, m, aromatic protons), 8.60 (1H, d, J ¼
0.8 Hz, C13AH), 8.68 (1H, dd, J ¼ 7.6 and 0.8 Hz, C1AH);
13C-NMR (CDCl3): 21.15(CH3), 25.45(CH2), 27.71(CH2),
55.25(OCH3), 113.89(CH), 114.16(C), 116.43(CH), 119.55(C),
12-Chloro-7-(4-Chlorophenyl)-5,6-dihydro-14-aza[1]benzo-
pyrano[3,4-b]phenanthren-8H-one (3l). White solid; Yield
47%; M.P. 255–256ꢁC; IR(KBr, cmꢀ1): 3050, 2970, 1730,
124.81(CH),
126.90(CH),
127.34(CH),
127.84(CH),
128.54(CH), 130.25(C), 130.93(CH), 132.16(C), 132.56(CH),
133.88(C), 133.99(C), 139.41(C), 150.70(C), 150.77(C),
152.07(C), 157.09(C), 159.07(C), 159.77(C¼¼O). Anal. Calcd.
for C28H21NO3: C, 80.17; H, 5.05; N, 3.34. Found: C, 80.05;
H, 5.01; N, 3.34.
12-Methyl-7-(4-Chlorophenyl)-5,6-dihydro-14-aza[1]benzo-
pyrano[3,4-b]phenanthren-8H-one (3h). Light yellow solid;
Yield 50%; M.P. 216–217ꢁC; IR(KBr, cmꢀ1): 3045, 2965,
1730, 1630, 1515, 820; 1H-NMR (CDCl3): d 2.56 (3H, s,
CH3), 2.69 (2H, t, protons at C6), 2.90 (2H, t, protons at C5),
1
1610, 1500, 825; H-NMR (CDCl3): d 2.69 (2H, t, protons at
C6), 2.89 (2H, t, protons at C5), 7.12–7.51 (9H, m, aromatic
protons), 8.63 (1H, poorly resolved dd, C1AH), 8.73 (1H,
poorly resolved d, C13AH); 13C-NMR (CDCl3): 25.46(CH2),
27.45(CH2), 113.74(C), 118.23(CH), 121.05(C), 124.64(CH),
127.06(CH),
127.53(CH),
127.95(CH),
128.66(CH),
128.87(CH), 130.00(C), 131.42(CH), 131.69(CH), 132.51(C),
133.40(C), 133.90(C), 136.18(C), 139.34(C), 149.54(C),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

844
D. I. Brahmbhatt, N. H. Patel, A. K. Patel, M. A. Patel, and V. G. Patel
Vol 48
[2] Lin, C. M.; Huang, S. T.; Lee, F. W.; Sawkuo, H.; Lin, M.
H. Bioorg Med Chem 2006, 14, 4402.
150.88(C), 150.95(C), 157.67(C), 158.99(C¼¼O). Anal. Calcd.
for C26H15Cl2NO2: C, 70.28; H, 3.40; N, 3.15. Found: C,
70.36; H, 3.45; N, 3.15.
[3] Massimo, C.; Francesco, E.; Federica, M.; Carla, M. M.;
Prieto, G. S.; Carlos, R. J. Aust J Chem 2003, 56, 59.
[4] Tyagi, Y. K.; Kumar, A.; Raj, H. G.; Vohra, P.; Gupta,
G.; Kumari, R.; Kumar, P.; Gupta, R. K. Eur J Med Chem 2005, 40,
413.
In case of the compounds 3e, 3h, 3j, and 3k, the number of
carbon signals in 13C-NMR spectra are less than expected (in
case of compounds 3e, 3h, and 3j, one signal, while in com-
pound 3k, two signals). This may be due to identical chemical
shifts of certain carbons which may appear at same position.
Antimicrobial activities. All the synthesized compounds
3a-l were screened for their antimicrobial activity using the
agar cup diffusion method [19]. Antibacterial activity of the
test compounds was evaluated against one gram-positive bacte-
ria, Bacillus subtilis, and one gram-negative bacteria, Esche-
richia coli, using Ciprofloxacin and Ampicillin as standard
drugs. Antifungal activity was screened against one fungal
strain, Candida albicans, using Clotrimazole as standard drug.
The zone of inhibition was measured in mm and was com-
pared with standard drug. DMF was used as blank. All the
compounds were tested at three different concentrations 500,
750, and 1000 lg/mL. The results are shown in Table 1.
[5] Modrana, J. N.; Nawrot, E.; Graczyk, J. Eur J Med Chem
2006, 41, 1301.
[6] Sardari, S.; Mori, Y.; Horita, K.; Micetich, R. G.; Nishibe,
S.; Dane-shtalab, M. Bioorg Med Chem 1999, 7, 1933.
[7] Huang, L.; Yuon, X.; Yu, D.; Lee, K. H.; Chin, H. C. Vi-
rology 2005, 332, 623.
[8] Elinos-Baez, C. M.; Leon, F.; Santos, E. Cell Biol Int 2005,
29, 703.
[9] Ukawa, K.; Ishiguro, T.; Wada, Y.; Nohara, A. Hetero-
cycles 1986, 24, 1931.
[10] Heber, D. Arch Pharm 1987, 320, 402.
[11] Heber, D. J Heterocycl Chem 1994, 31, 1353.
[12] Pandya, S. U.; Pandya, U. R.; Hirani, B. R.; Brahmbhatt, D.
I. J Heterocycl Chem 2006, 43, 795.
[13] Naik, H. R. P.; Naik, H. S. B.; Naik, T. R. R.; Naika, H.
R.; Gouthamchandra, K.; Mahmood, R.; Ahamed, B. M. K. Eur J Med
Chem 2009, 44, 981.
Acknowledgments. The authors NHP and VGP are thankful to
UGC for meritorious research fellowship under RFSMS. The
authors are also thankful to the Head, Department of Chemistry,
Sardar Patel University, for providing research facilities and
Vaibhav Laboratory, Ahmedabad, for recording IR spectra.
[14] Willemann, C.; Grunert, R.; Bednarski, P. J.; Troschutz, R.
Bioorg Med Chem 2009, 17, 4406.
[15] Murthy, M.; Pedemonte, N.; Vinish, L. M.; Galietta, L.;
Cuthbert, A. Eur J Pharmacol 2005, 516, 118.
[16] Zarghi, A.; Ghodsi, R.; Azizi, E.; Daraie, B.; Hedayati M.;
Dadrass O. G. Bioorg Med Chem 2009, 17, 5312.
[17] Shah, V. R.; Bose, J. L.; Shah R. C. J Org Chem 1960, 25,
677.
REFERENCES AND NOTES
[1] (a) Geissman, T. A. The Chemistry of Flavonoid Com-
pounds; Pergamon Press: Oxford, 1962; (b) Harborne, J. B. The Flavo-
noid: The Advances in Research since 1980; Chapman & Hall:
London, 1988; (c) Harborne, J. B. The Flavonoid: The Advances in
Research since 1986; Chapman & Hall: London, 1994.
[18] Rao, C. J.; Reddy, K. M.; Murthy, A. K. Indian J Chem
1981, 20B, 282.
[19] Copper, K. E.; Kavanagh, F. Analytical Microbiology, 2nd
ed.; Academic Press: New York, 1972, pp 13.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet