Synthesis and Antibacterial Activity Evaluation of Novel (E)-4-(4-((arylidene)amino)phenoxy)coumarin Derivatives

Article abstract of DOI:10.1002/jhet.2691

A series of novel (E)-4-(4-((arylidene)amino)phenoxy)coumarin derivatives were synthesized from 4-hydroxycoumarin in three step reactions, and their antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas citri subsp. Citri (X

Full text of DOI:10.1002/jhet.2691

Month 2016
Synthesis and Antibacterial Activity Evaluation of Novel (E)-4-
(4-((arylidene)amino)phenoxy)coumarin Derivatives
a
a
a
Mei-Hang Chen,a,b Bang-Cheng Tang, Xun Zhang, and Hua Shu
*
*
aDepartment of Material and Chemistry Engineering, Tongren University, Bijiang District, Tongren, Guizhou 554300,
China
bState Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide
and Agricultural Bioengineering, Ministry of Education, Guizhou University, Huaxi District, Guiyang 550025, China
*
E-mail: chenmeihang0123@126.com; shuhua1223@126.com
Received September 29, 2015
DOI 10.1002/jhet.2691
Published online 00 Month 2016 in Wiley Online Library (wileyonlinelibrary.com).
A series of novel (E)-4-(4-((arylidene)amino)phenoxy)coumarin derivatives were synthesized from
4-hydroxycoumarin in three step reactions, and their antibacterial activities against Xanthomonas oryzae
pv. oryzae (Xoo) and Xanthomonas citri subsp. Citri (Xcc) in vitro were evaluated. Result found that most
of the target compounds exhibited pronounced antibacterial activities. Among the target compounds, 3f,
3g, 3h, 3i, 3j, 3n, 3o, and 3p exhibited excellent antibacterial activities against Xoo, with EC50 values of
143.9, 127.4, 133.8, 145.8, 138.4, 116.9, 134.6, and 121.8 μg/mL, respectively, which were better than that
of thiadiazole copper (203.6 μg/mL). Moreover, compounds 3f, 3g, 3h, 3i, 3j, 3n, 3o, and 3p showed good
antibacterial activities against Xcc, with EC50 values of 118.4, 126.3, 117.2, 105.3, 102.3, 95.2, 96.0, and
88.2 μg/mL, respectively, which were similar to that of thiadiazole copper (138.3 μg/mL).
J. Heterocyclic Chem., 00, 00 (2016).
INTRODUCTION
pyrimidin-2-ones exhibited pronounced antimycobacterial
and antimicrobial activities [20]. Moreover, imines deriv-
atives have gained attention because of showing extensive
biological activities [21–27]. Some of the imine deriva-
tives containing the 4(3H)-quinazolinone moiety can ef-
fectively control tobacco bacterial wilt, tomato bacterial
wilt, and Xoo [28]. Our research group is interested in
imine derivatives and synthesized a serial of novel Schiff
base derivatives containing quinazolin-4(3H)-one moiety
with antibacterial properties against tobacco and tomato
bacterial wilt (Chen, M.-H.; Wang, X.-B.; Tang, B.-C.;
Zhang, X. Synthesis and antibacterial evaluation of novel
Schiff base derivatives containing 4(3H)-quinazolinone
moiety. Submitted.). For further study of antibacterial ac-
tivity of novel imine derivatives we synthesized a series
of (E)-4-(4-((arylidene)amino)phenoxy)coumarin deriva-
tives and evaluated their antibacterial activities against
Xoo and Xcc in vitro and the structure-activity relation-
ship (SAR) analyses of antibacterial activity were also
discussed.
The bacterial genus Xanthomonas comprises a number
of gram-negative plant pathogenic bacteria that cause a va-
riety of severe plant diseases [1]; Xanthomonas oryzae pv.
oryzae (Xoo) and Xanthomonas citri subsp. Citri (Xcc) are
two kinds of important Xanthomonas species, which lead
to defoliation, dieback and fruit drop, reducing yields,
and causing billions of dollars of economic losses world-
wide [2]. The pathogen can also be spread by people di-
rectly and potentially on various surfaces including plant
material, clothing, and various equipment or implements
[3]. To date, some of the traditional bactericides
(thiadiazole copper, kocide, and streptomycin) and control
methods are insufficient to manage the disease [4,5].
Therefore, development of novel antibacterial agents re-
mains a daunting task in pesticide science.
Coumarin, the most important classes of benzopyrones,
belongs to natural as well as synthetic origin that exhibits
diverse biological activities, including anticoagulants [6],
anticancer [7–11], antioxidant [12], anti-HIV [13],
antimalarial [14,15], anti-depressant-like [16], and antimi-
crobial [17] activities. Previous research on coumarin-6-
sulfonamides with a free C4-azidomethyl group as
antimicrobials was reported [18]. During recent years,
some of researches demonstrated that novel iodinated-4-
aryloxymethylcoumarins derivatives exhibited potent
anticancer and antimycobacterial activities [19], and
coumarin containing isoxazoles, pyrimidinthiones, and
RESULTS AND DISCUSSION
Chemistry.
The synthetic route of novel (E)-4-(4-
((arylidene)amino)phenoxy)coumarin derivatives was shown
in Scheme 1. The title compounds were synthesized from
4-hydroxycoumarin in three steps including chlorination,
etherification, and condensation reactions. The structures of
© 2016 Wiley Periodicals, Inc.

M.-H. Chen, B.-C. Tang, X. Zhang, and H. Shu
Vol 000
Scheme 1. Synthetic route of the title compounds 3a–3p.
the synthesized compounds were confirmed on the basis of
IR, NMR spectra, and elemental analysis. The IR spectral
data of compounds 3a–3p showed characteristic
, which were
assigned to C = O of coumarin. The characteristic
exhibited appreciable antibacterial activities against Xoo
and Xcc. Among the title compounds, 3f, 3g, 3h, 3i, 3j,
3n, 3o, and 3p showed excellent antibacterial activities
against Xoo at 200μg/mL, with the inhibition rates of
83.5%, 86.2%, 81.8%, 80.3%, 87.8%, 97.3%, 94.2% and
96.5%, respectively, which were better than that of the
commercial bactericide thiadiazole copper (68.7%). The
antibacterial activities of compounds 3f, 3g, 3h, 3i, 3j, 3k,
3l, 3m, 3n, 3o, and 3p against Xoo at 100μg/mL are
40.5%, 43.6%, 44.1%, 42.5%, 46.6%, 43.3%, 43.9%,
43.1%, 54.2%, 48.7%, and 50.4%, respectively, which
were better than that of thiadiazole copper (33.5%).
Additionally, compounds 3f, 3g, 3j, 3n, 3o, and 3p
demonstrated good antibacterial activities against Xcc, with
the inhibition rates of 80.7%, 85.4%, 87.4%, 96.1%,
95.3%, and 93.6%, respectively, which were superior to
that of thiadiazole copper (76.2%) at 200μg/mL.
absorption bands at 1723–1709 cmꢀ1
ꢀCH = Nꢀ stretching bands were observed at about
1
1630ꢀ1621 cmꢀ1. In the H NMR spectra, depending on
the structure, the characteristic H3 of coumarin cycle
were observed as a signal at about 5.30ꢀ5.25 ppm. A
singlet ranging from 8.95ꢀ8.58 ppm belonged to –
N = CHꢀ proton. The chemical shifts at 162.59ꢀ161.63
and 161.70ꢀ154.04 ppm confirmed the existence of
C = O, and ꢀN = CHꢀ groups in 13C NMR, respectively.
Antibacterial activity. The synthesized compounds (3a–
3p) were evaluated for antibacterial activity against Xoo and
Xcc in vitro. Biology results were listed in Table 2 and
indicated that most of the synthesized compounds
Table 1
Antibacterial activities of the target compounds 3a–3p against Xoo and Xcc in vitro.
Xoo
Xcc
Compd.
Ar
Ph
4-MePh
4-OMePh
2-OMePh
3,4-diOMePh
2-FPh
4-FPh
4-ClPh
2-ClPh
2-F-6-ClPh
4-BrPh
200 μg/mL
100 μg/mL
200 μg/mL
100 μg/mL
3a
3b
3c
3d
3e
3f
3 g
3 h
3i
3j
3 k
3 l
3 m
3n
3o
3p
56.8 1.7
48.2 2.6
46.7 1.9
47.2 1.7
39.1 2.8
83.5 2.4
86.2 2.5
81.8 1.2
80.3 3.2
87.8 1.4
78.2 2.5
75.2 1.5
77.0 3.2
97.3 2.7
94.2 2.0
96.5 1.1
68.7 2.1
35.3 2.4
27.1 2.6
25.0 1.0
25.5 2.8
26.1 1.2
40.5 2.5
43.6 1.2
44.1 1.2
42.5 2.7
46.6 1.8
43.3 1.6
43.9 2.5
43.1 2.7
54.2 3.5
48.7 2.0
50.4 1.8
33.5 1.7
60.1 2.1
43.4 2.5
40.3 1.5
41.8 2.3
40.4 2.0
80.7 2.6
85.4 2.3
72.7 2.3
74.8 2.7
87.4 1.6
78.7 2.7
73.8 2.1
70.3 1.8
96.1 1.5
95.3 1.4
93.6 2.5
76.2 1.3
32.8 1.5
24.5 2.4
27.3 3.3
29.2 2.7
20.4 2.5
52.8 2.4
57.1 2.5
55.6 2.5
53.0 2.6
57.9 1.7
46.1 3.5
42.1 3.4
43.2 4.1
58.1 2.2
62.6 3.2
58.3 2.6
51.2 1.2
3-BrPh
2-BrPh
4-NO2Ph
3-NO2Ph
2-NO2Ph
Thiadiazole copper
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2016
Novel (E)-4-(4-((arylidene)amino)phenoxy)coumarin Derivatives with Antibacterial Activity
Table 2
2-NO2C6H4, 3-NO2C6H4, and 4-NO2C6H4, the corre-
sponding compounds exhibited shown excellent anti-
bacterial activities against Xcc. Compounds with 4-
MeC6H4, 4-OMeC6H4, and 2-OMeC6H4 also showed
unsatisfactory antibacterial activities against Xcc. There-
fore, SAR results indicated that compounds with
electron-withdrawing groups (Cl, F, and NO2) exhibited
excellent antibacterial activities against Xoo and Xcc,
and compounds with electron-donating groups (Me and
OMe) showed poor antibacterial activities against Xoo
and Xcc.
EC50 values of the target compounds 3a–3p against Xoo and Xcc.
EC50 (μg/mL)
Compd.
Xoo
Xcc
3a
3b
3c
3d
3e
3f
3 g
3 h
3i
3j
3 k
3 l
3 m
3n
3o
3p
273.2 1.3
260.5 2.0
290.9 1.6
287.5 2.0
308.3 1.7
143.9 2.6
127.4 2.0
133.8 1.6
145.8 2.1
138.4 2.7
180.4 3.2
186.8 1.9
172.1 2.5
116.9 1.7
134.6 2.5
121.8 1.6
203.6 3.0
235.1 2.7
274.1 1.1
303.4 1.6
294.3 2.3
336.1 3.5
118.4 2.0
126.3 1.4
117.2 2.6
105.3 1.7
102.3 2.1
145.6 1.3
153.1 2.5
149.0 1.8
95.2 1.2
CONCLUSIONS
In summary, a series of novel (E)-4-(4-((arylidene)
amino)phenoxy)coumarin derivatives have been synthe-
sized and evaluated for antibacterial activities against
Xoo and Xcc in vitro. Result found that the target com-
pounds exhibited pronounced antibacterial activities.
Among the target compounds, 3f, 3g, 3h, 3i, 3j, 3n,
3o, and 3p exhibited excellent antibacterial activities
against Xoo, with EC50 values of 143.9, 127.4, 133.8,
145.8, 138.4, 116.9, 134.6, and 121.8 μg/mL, respec-
tively, which were better than that of thiadiazole copper
(203.6 μg/mL). Compounds 3f, 3g, 3h, 3i, 3j, 3n, 3o,
and 3p showed good antibacterial activities against
Xcc, with EC50 values of 118.4, 126.3, 117.2, 105.3,
102.3, 95.2, 96.0, and 88.2 μg/mL, respectively, which
were similar to that of thiadiazole copper (138.3 μg/
mL). SAR results indicated that compounds with
electron-withdrawing groups (Cl, F, and NO2) exhibited
excellent antibacterial activities against Xoo and Xcc,
and compounds with electron-donating groups (Me and
OMe) showed poor antibacterial activities against Xoo
and Xcc. To the best of our knowledge, it is the first re-
port on the synthesis and antibacterial activities of novel
(E)-4-(4-((arylidene)amino)phenoxy)coumarin
96.0 2.2
88.2 3.0
138.3 1.3
Thiadiazole copper
Compounds 3f, 3g, 3h, 3i, 3j, 3n, 3o, and 3p showed good
antibacterial activities against Xcc (52.8%, 57.1%, 55.6%,
53.0%, 57.9%, 58.1%, 62.6%, and 58.3%, respectively) at
100μg/mL compared with thiadiazole copper (51.2%).
Based on the preliminary bioassays, the EC50 values of
the test compounds as well as thiadiazole copper were
summarized in Table 2. Notably, compounds 3f, 3g, 3h,
3i, 3j, 3n, 3o, and 3p exhibited excellent antibacterial ac-
tivities against Xoo, with EC50 values of 143.9, 127.4,
133.8, 145.8, 138.4, 116.9, 134.6, and 121.8 μg/mL, re-
spectively, which were better than that of thiadiazole-
copper (203.6 μg/mL). Meanwhile, compounds 3f, 3g,
3h, 3i, 3j, 3n, 3o, and 3p showed good antibacterial activ-
ities against Xcc in vitro, with EC50 values of 118.4, 126.3,
117.2, 105.3, 102.3, 95.2, 96.0, and 88.2 μg/mL, respec-
tively, which were similar to that of thiadiazole copper
(138.3 μg/mL). Moreover, compounds 3a, 3b, 3c, 3d, and
3e showed poor antibacterial activities against Xoo and
Xcc.
derivatives.
As an extension of this approach, the SAR were de-
duced on the basis of the activity values in Tables 1
and 2. It was found that the type of Ar substituted
groups has significant effect on antibacterial activities
of the target compounds. When Ar is 2-FC6H4, 4-
FC6H4, 2-ClC6H4, 4-ClC6H4, 2-BrC6H4, 4-BrC6H4, 3-
BrC6H4, 2-F-6-ClC6H3, 2-NO2C6H4, 3-NO2C6H4, and
4-NO2C6H4, the corresponding compounds exhibited
excellent antibacterial activities against Xoo. On the
other hand, when Ar is 4-MeC6H4, 4-OMeC6H4, and
2-OMeC6H4, the corresponding title compounds exhib-
ited poor antibacterial activities against Xoo. Mean-
while, it was interesting to note that when Ar is 2-
FC6H4, 4-FC6H4, 2-ClC6H4, 4-ClC6H4, 2-F-6-ClC6H3,
EXPERIMENTAL
General procedures.
The melting points of the
products were determined on an XT-4 binocular
microscope (Beijing Tech Instrument Co., China). 1H
NMR and 13C NMR (solvent DMSO-d6) spectral
analyses were performed on a JEOL-ECX 500 NMR
spectrometer at room temperature using TMS as an
internal standard. The IR spectra were recorded on a
Bruker Vector 22 spectrometer in a KBr disk (Bruker
Corporation, Switzerland). Elemental analysis was
performed on an Elementar Vario-III CHN analyzer. All
solvents were dried and redistilled before used.
Journal of Heterocyclic Chemistry
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M.-H. Chen, B.-C. Tang, X. Zhang, and H. Shu
Vol 000
General procedure for synthesis of 4-chlorocoumarin
1H, coumarin-3-H), 2.39 (s, 3H, CH3); 13C NMR
(DMSO-d6, 125 MHz, ppm) δ: 166.52, 161.93, 161.70,
153.63, 150.56, 150.45, 142.29, 133.97, 133.88,
130.01, 129.35, 125.07, 123.59, 123.49, 122.62,
117.16, 115.34, 93.39, 21.74; MS (ESI) m/z: 356.2
([M + H]+); Anal. Calcd. for C22H18N2O2: C, 77.73; H,
4.82; N, 3.94. Found: C, 77.91; H, 4.47; N, 4.03.
(E)-4-(4-((4-methoxybenzylidene)amino)phenoxy)coumarin
(1).
This compound was synthesized by following
literature known methods [29].
General procedure for synthesis of 4-(4-aminophenoxy)
coumarin (2).
A mixture of compound 1 (1.0 mmol),
4-aminophenol (1.0 mmol), and K2CO3 (1.2 mmol) was
dissolved in CH3CN (30 mL) and refluxed. After
refluxing for 4 h, the reaction solution was poured into
ice water to produce solid precipitates. The resulting
precipitates were then filtered and washed with water.
The purified compound 2 were recrystallized from ethanol.
(3c).
Brown solid; mp 203–205°C; yield, 69.6%; IR
1
(KBr): 1717, 1623, 1602, 1183cmꢀ1; H NMR (DMSO-
d6, 500MHz, ppm) δ: 8.61 (s, 1H, CH=N), 8.07 (d, 1H,
J =8.0Hz, coumarin-5-H), 7.92 (d, 2H, J=7.5 Hz, Ar-H),
7.78 (t, 1H, J =7.0Hz, coumarin-7-H), 7.51–7.40 (m, 6H,
coumarin-6,8-H, Ar-H), 7.10 (d, 2H, J=8.5Hz, Ar-H),
5.25 (s, 1H, coumarin-3-H), 3.85 (s, 3H, OCH3); 13C
NMR (DMSO-d6, 125MHz, ppm) δ: 166.55, 162.59,
161.71, 161.33, 153.63, 150.77, 150.24, 133.96, 131.15,
129.31, 125.07, 123.58, 123.41, 122.58, 117.16, 115.34,
114.84, 93.36, 55.91; MS (ESI) m/z: 372.2 ([M+H]+);
Anal. Calcd. for C23H17NO4: C, 74.38; H, 4.61; N, 3.77.
Found: C, 74.55; H, 4.43; N, 3.62.
4-(4-Aminophenoxy)coumarin (2).
Brown solid; mp
163–165°C; yield 84.8%; 1H NMR (DMSO-d6,
500MHz, i>:/i>: 8.17 (d, 1H, J = 7.0 Hz, Coumarin-5-H),
7.60 (t, 1H, J= 5.0 Hz, coumarin-7-H), 7.34–7.30 (m, 2H,
Coumarin-6,8-H); 6.95 (d, 2H, J = 8.5 Hz, Ar-H), 6.62 (d,
2H, J =8.5 Hz, Ar-H), 5.22 (s, 2H, NH2), 4.95 (s, 1H,
coumarin-3-H); 13C NMR (DMSO-d6, 125 MHz, ppm) δ:
166.37, 161.83, 153.64, 151.52, 133.86, 131.13, 125.04,
123.49, 117.14, 112.72, 107.86, 106.08, 93.06; MS (ESI)
m/z: 254.2 ([M+ H]+).
(E)-4-(4-((2-methoxybenzylidene)amino)phenoxy)coumarin
General procedure for synthesis of title compounds
(3aꢀ3p). Aromatic aldehyde (1.2 mmol) was added to a
solution of 4-(4-aminophenoxy)-2H-chromen-2-one (2)
(1.0 mmol) in anhydrous ethanol (15 mL). The resulting
mixture was refluxed for 1–2 h. Upon completion of
reaction, the solvent was removed under depressurization,
and the residue was recrystallized from ethanol. The
product was then filtered, washed, and dried to obtain
(E)-4-(4-((arylidene)amino)phenoxy)-2H-chromen-2-one
(3d).
Brown solid; mp 207–210°C; yield, 78.6%; IR
1
(KBr): 1723, 1625, 1608, 1173cmꢀ1; H NMR (DMSO-
d6, 500MHz, ppm) δ: 8.90 (s, 1H, CH=N), 8.08 (d, 1H,
J =8.0Hz, coumarin-5-H), 8.04 (d, 1H, J=7.5 Hz, Ar-H),
7.78 (t, 1H, J =7.0Hz, coumarin-7-H), 7.57–7.38 (m, 7H,
coumarin-6,8-H, Ar-H), 7.19-7.02 (m, 2H, Ar-H), 5.27 (s,
1H, coumarin-3-H), 3.91 (s, 3H, OCH3); 13C NMR
(DMSO-d6, 125MHz, ppm) δ: 166.50, 161.71, 159.92,
156.97, 153.64, 151.10, 150.46, 133.97, 127.42, 125.08,
124.21, 123.60, 122.66, 121.24, 117.16, 15.35, 112.62,
93.43, 56.33; MS (ESI) m/z: 372.2 ([M+H]+); Anal.
Calcd. for C23H17NO4: C, 74.38; H, 4.61; N, 3.77.
Found: C, 74.46; H, 4.39; N, 3.62.
derivatives. The physical characteristics, IR, 1H NMR, 13
C
NMR, and elemental analysis data for all the target
compounds were shown below.
(E)-4-(4-((benzylidene)amino)phenoxy)coumarin (3a).
White solid; mp 192–194°C; yield, 70.1%; IR (KBr):
1713, 1630, 1608, 1186cmꢀ1 1H NMR (DMSO-d6,
;
(E)-4-(4-((3,4-dimethoxybenzylidene)amino)phenoxy)
coumarin (3e).
Brown solid; mp 214–216°C; yield,
500MHz, ppm) δ: 8.70 (s, 1H, CH =N), 8.08 (d, 1H,
J =8.0 Hz, coumarin-5-H), 7.98(d, 2H, J = 7.5 Hz, Ar-H),
7.78 (t, 1H, J= 7.0 Hz, coumarin-7-H), 7.56–7.42 (m, 9H,
coumarin-6,8-H, Ar-H), 5.26 (s, 1H, coumarin-3-H); 13C
NMR (DMSO-d6, 125MHz, ppm) δ: 166.51, 162.19,
161.70, 153.64, 150.60, 150.43, 136.39, 133.97, 132.23,
129.41, 129.33, 125.08, 123.60 123.54, 122.66, 117.16,
115.34; MS (ESI) m/z: 342.1 ([M + H]+); Anal. Calcd. for
C22H15NO3: C, 77.41; H, 4.43; N, 4.10. Found: C, 77.16;
H, 4.48; N, 4.31.
73.1%; IR (KBr): 1709, 1624, 1606, 1185 cmꢀ1 1H
;
NMR (DMSO-d6, 500 MHz, ppm) δ: 8.58 (s, 1H,
CH = N), 8.07 (d, 1H, J = 8.0 Hz, coumarin-5-H), 7.78
(t, 1H, J = 7.0 Hz, coumarin-7-H), 7.57–7.38 (m, 7H,
coumarin-6,8-H, Ar-H), 7.12 (d, 1H, J = 8.0 Hz, Ar-H),
5.27 (s, 1H, coumarin-3-H), 3.85 (s, 2H, 2OCH3); 13C
NMR (DMSO-d6, 125 MHz, ppm) δ: 166.53, 161.71,
161.58, 153.63, 152.51, 150.75, 150.23, 149.54,
133.95, 129.40, 125.06, 124.87, 123.57, 122.59,
117.15, 115.34, 111.80, 109.81, 93.35, 56.18, 55.97;
MS (ESI) m/z: 402.2 ([M + H]+); Anal. Calcd. for
C24H19NO5: C, 71.81; H, 4.77; N, 3.49. Found: C,
71.66; H, 4.88; N, 3.37.
(E)-4-(4-((4-methylbenzylidene)amino)phenoxy)coumarin
(3b).
White solid; mp 197–199°C; yield, 78.0%; IR
(KBr): 1722, 1623, 1606, 1186 cmꢀ1 1H NMR
;
(DMSO-d6, 500 MHz, ppm) δ: 8.65 (s, 1H, CH = N),
8.07 (d, 1H, J = 8.0 Hz, coumarin-5-H), 7.86 (d, 2H,
J = 7.5 Hz, Ar-H), 7.77 (t, 1H, J = 7.0 Hz, coumarin-7-
H), 7.51–7.34 (m, 8H, coumarin-6,8-H, Ar-H), 5.25 (s,
(E)-4-(4-((2-fluorobenzylidene)amino)phenoxy)coumarin
(3f).
Gray solid; mp 210–213°C; yield, 80.2%; IR
(KBr): 1723, 1622, 1606, 1172 cmꢀ1 1H NMR
;
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DOI 10.1002/jhet

Month 2016
Novel (E)-4-(4-((arylidene)amino)phenoxy)coumarin Derivatives with Antibacterial Activity
(DMSO-d6, 500 MHz, ppm) δ: 8.84 (s, 1H, CH = N),
8.13 (t, 1H, J = 6.5 Hz, Ar-H), 8.08 (d, 1H, J = 8.0 Hz,
coumarin-5-H), 7.77 (t, 1H, J = 7.0 Hz, coumarin-7-H),
(E)-4-(4-((2-chloro-6-fluorobenzylidene)amino)phenoxy)
coumarin (3j).
Brown solid; mp 219–221°C; yield,
70.1%; IR (KBr): 1714, 1623, 1608, 1176 cmꢀ1 1H
;
7.64-7.61
(
m, 1H, Ar-H), 7.51–7.37 (m, 8H,
NMR (DMSO-d6, 500 MHz, ppm) δ: 8.80 (s, 1H,
CH = N), 8.08 (d, 1H, J = 8.0 Hz, coumarin-5-H), 7.77
(t, 1H, J = 8.0 Hz, coumarin-7-H), 7.61–7.58 (m, 1H,
Ar-H), 7.51–7.39 ( m, 8H, coumarin-6,8-H, Ar-H),
5.30 (s, 1H, coumarin-3-H); 13C NMR (DMSO-d6,
125 MHz, ppm) δ: 166.38, 161.68, 155.57, 151.19,
150.23, 135.36, 133.97, 133.68, 133.61, 126.83,
125.08, 123.60, 123.49, 122.82, 117.15, 116.43,
116.26, 115.33, 93.56; MS (ESI) m/z: 394.1 ([M
+ H]+); Anal. Calcd. for C22H18N2O2: C, 67.10; H,
3.33; N, 3.56. Found: C, 67.19; H, 3.67; N, 3.70.
coumarin-6,8-H, Ar-H), 5.28 (s, 1H, coumarin-3-H);
13C NMR (DMSO-d6, 125 MHz, ppm) δ: 166.44,
161.70, 154.84, 153.64, 150.91, 150.24, 134.36,
133.97, 128.44, 125.50, 125.08, 123.67, 123.70,
122.70, 117.16, 116.87, 116.71, 115.34, 93.49; MS
(ESI) m/z: 360.1 ([M + H]+); Anal. Calcd. for
C22H18N2O2: C, 73.53; H, 3.93; N, 3.90. Found: C,
73.68; H, 3.84; N, 3.73.
(E)-4-(4-((4-fluorobenzylidene)amino)phenoxy)coumarin
(3g).
Gray solid; mp 209–211°C; yield, 64.1%; IR
(KBr): 1718, 1623, 1608, 1186 cmꢀ1 1H NMR
;
(E)-4-(4-((4-bromobenzylidene)amino)phenoxy)coumarin
(DMSO-d6, 500 MHz, ppm) δ: 8.63 (s, 1H, CH = N),
8.08 (d, 1H, J = 7.0 Hz, coumarin-5-H), 7.97 (d, 2H,
J = 8.5 Hz, Ar-H), 7.78 (t, 1H, J = 8.0 Hz, coumarin-7-
H), 7.65 (d, 2H, J = 8.5 Hz, Ar-H), 7.54–7.39 (m, 6H,
coumarin-6,8-H, Ar-H), 5.27 (s, 1H, coumarin-3-H);
13C NMR (DMSO-d6, 125 MHz, ppm) δ: 166.41,
161.63, 160.91, 153.60, 151.76, 150.22, 136.43,
135.29, 133.97,130.92, 128.56, 125.15, 123.62, 123.44,
122.68, 117.19, 115.45; MS (ESI) m/z: 360.1 ([M
+ H]+); Anal. Calcd. for C22H18N2O2: C, 73.53; H,
3.93; N, 3.90. Found: C, 73.59; H, 3.79; N, 3.88.
(3k).
Gray solid; mp 229–231°C; yield, 72.8%; IR
(KBr): 1716, 1622, 1608, 1183 cmꢀ1 1H NMR
;
(DMSO-d6, 500 MHz, ppm) δ: 8.71 (s, 1H, CH = N),
8.07 (d, 1H, J = 8.0 Hz, coumarin-5-H), 7.91 (d, 1H,
J = 8.0 Hz, Ar-H), 7.78–7.75 (m, 3H, coumarin-7-H,
Ar-H), 7.51–7.42 ( m, 6H, coumarin-6,8-H, Ar-H),
5.25 (s, 1H, coumarin-3-H); 13C NMR (DMSO-d6,
125 MHz, ppm) δ: 166.47, 161.69, 161.10, 153.64,
150.78, 150.06, 135.57, 133.98, 132.49, 131.11,
125.79, 125.08, 123.63, 122.69, 117.16, 115.33, 93.45;
MS (ESI) m/z: 420.1 ([M + H]+); Anal. Calcd. for
C22H18N2O2: C, 62.87; H, 3.36; N, 3.33. Found: C,
62.69; H, 3.48; N, 3.47.
(E)-4-(4-((4-chlorobenzylidene)amino)phenoxy)coumarin
(3h).
Gray solid; mp 214–216°C; yield, 81.3%; IR
(KBr): 1717, 1621, 1608, 1183 cmꢀ1 1H NMR
;
(E)-4-(4-((2-bromobenzylidene)amino)phenoxy)coumarin
(DMSO-d6, 500 MHz, ppm) δ: 8.72 (s, 1H, CH = N),
8.07 (d, 1H, J = 7.0 Hz, coumarin-5-H), 7.99 (d, 2H,
J = 8.5 Hz, Ar-H), 7.78 (t, 1H, J = 8.0 Hz, coumarin-7-
H), 7.62 (d, 2H, J = 8.5 Hz, Ar-H), 7.51–7.37 (m, 6H,
coumarin-6,8-H, Ar-H), 5.26 (s, 1H, coumarin-3-H);
13C NMR (DMSO-d6, 125 MHz, ppm) δ: 166.47,
161.69, 160.94, 153.63, 150.76, 150.07, 136.77,
135.25, 133.97,130.92, 129.56, 125.07, 123.62, 123.57
122.68, 117.15, 115.32; MS (ESI) m/z: 376.1 ([M
+ H]+); Anal. Calcd. for C22H18N2O2: C, 70.31; H,
3.75; N, 3.73. Found: C, 70.15; H, 3.83; N, 3.90.
(E)-4-(4-((2-chlorobenzylidene)amino)phenoxy)coumarin
(3l).
Gray solid; mp 235–237°C; yield, 70.9%; IR
(KBr): 1722, 1624, 1608, 1175 cmꢀ1 1H NMR
;
(DMSO-d6, 500 MHz, ppm) δ: 8.85 (s, 1H, CH = N),
8.17 (d, 1H, J = 7.5 Hz, Ar-H), 8.07 (d, 1H, J = 8.0 Hz,
coumarin-5-H), 7.79–7.75 (m, 2H, coumarin-7-H, Ar-
H), 7.57–7.46 ( m, 8H, coumarin-6,8-H, Ar-H), 5.30 (s,
1H, coumarin-3-H); 13C NMR (DMSO-d6, 125 MHz,
ppm) δ: 166.39, 161.68, 160.09, 153.64, 151.04,
149.99, 134.36, 133.91, 129.42, 128.7, 126.01, 125.07,
123.66, 123.59, 122.81, 117.15, 115.33, 93.55; MS
(ESI) m/z: 420.1 ([M + H]+); Anal. Calcd. for
C22H18N2O2: C, 62.87; H, 3.36; N, 3.33. Found: C,
62.72; H, 3.56; N, 3.41.
(3i).
Gray solid; mp 208–210°C; yield, 68.7%; IR
(KBr): 1715, 1621, 1606, 1183 cmꢀ1 1H NMR
;
(E)-4-(4-((3-bromobenzylidene)amino)phenoxy)coumarin
(DMSO-d6, 500 MHz, ppm) δ: 8.93 (s, 1H, CH = N),
8.20 (d, 2H, J = 7.5 Hz, Ar-H), 8.07 (d, 1H, J = 8.0 Hz,
coumarin-5-H), 7.78 (t, 1H, J = 8.0 Hz, coumarin-7-H),
7.62–7.43 ( m, 9H, coumarin-6,8-H, Ar-H), 5.30 (s, 1H,
coumarin-3-H); 13C NMR (DMSO-d6, 125 MHz, ppm)
δ: 166.40, 161.68, 157.77, 153.64, 151.03, 150.08,
135.71, 133.96, 133.70, 133.02, 130.67, 128.99,
128.25, 125.07, 123.69, 123.59, 122.77, 117.15,
115.33, 93.53; MS (ESI) m/z: 376.1 ([M + H]+); Anal.
Calcd. for C22H18N2O2: C, 70.31; H, 3.75; N, 3.73.
Found: C, 70.15; H, 3.83; N, 3.90.
(3m).
Gray solid; mp 231–233°C; yield, 65.1%; IR
(KBr): 1717, 1622, 1608, 1184 cmꢀ1 1H NMR
;
(DMSO-d6, 500 MHz, ppm) δ: 8.70 (s, 1H, CH = N),
8.13 (s, 1H, Ar-H), 8.07 (d, 1H, J = 8.0 Hz, coumarin-5-
H), 7.96(d, 1H, J = 8.0 Hz, Ar-H), 7.78–7.75 (m, 2H,
coumarin-7-H, Ar-H), 7.50–7.45 ( m, 7H, coumarin-6,8-
H, Ar-H), 5.26 (s, 1H, coumarin-3-H); 13C NMR
(DMSO-d6, 125 MHz, ppm) δ: 166.44, 161.69, 160.71,
153.64, 150.91, 149.85, 138.68, 134.72, 133.98, 131.64,
131.52, 128.29, 125.09, 123.70, 123.59, 122.71, 117.16,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

M.-H. Chen, B.-C. Tang, X. Zhang, and H. Shu
Vol 000
115.33; MS (ESI) m/z: 420.1 ([M + H]+); Anal. Calcd. for
C22H18N2O2: C, 62.87; H, 3.36; N, 3.33. Found: C,
62.72; H, 3.43; N, 3.54.
2.5 g peptone, 0.5 g yeast powder, 5.0 g glucose, and
500 mL distilled water, pH7.0 ꢀ 7.2) liquid medium in
4 mL tubes. Then, 40 μL of NB medium containing
tobacco bacterial wilt was added to 5 mL of solvent NB
medium containing the test compounds or thiadiazole-
copper. The inoculated test tubes were incubated at 30
1°C with continuous shaking at 180rpm for 48h.
Culture growth was monitored with a spectrophotometer
by measuring the optical density at 600nm (OD600) given
by corrected turbidity values [28]. The relative inhibitory
rate I of the circle mycelium compared with a blank
assay was calculated as follows:
(E)-4-(4-((4-nitrobenzylidene)amino)phenoxy)coumarin
(3n).
Yellow solid; mp >250°C; yield, 79.1%; IR
(KBr): 1713, 1623, 1608, 1183 cmꢀ1 1H NMR
;
(DMSO-d6, 500 MHz, ppm) δ 8.95 (s, 1H, CH = N),
8.21 (d, 1H, J = 7.0 Hz, Ar-H), 8.15 (d, 1H, J = 8.5 Hz,
Ar-H), 8.08 (d, 1H, J = 8.0 Hz, coumarin-5-H), 7.92 (t,
1H, J = 8.5 Hz, Ar-H), 7.82–7.75 (M, 2H, Ar-H), 7.51–
7.46 ( m, 6H, coumarin-6,8-H, Ar-H), 5.30 (s, 1H,
coumarin-3-H); 13C NMR (DMSO-d6, 125 MHz, ppm)
δ 166.34, 161.66, 158.23, 153.63, 151.21, 149.85,
149.62, 134.36, 133.97, 132.60, 130.43, 130.11,
125.11, 125.07, 123.77, 123.58, 122.83, 117.15,
115.31; MS (ESI) m/z: 387.1 ([M + H]+); Anal. Calcd.
for C22H18N2O2: C, 68.39; H, 3.56; N,7.25. Found: C,
68.14; H, 3.42; N, 7.13.
Ið%Þ ¼ ðCtur ꢀ TturÞ=Cturꢁ 100:
Ctur is the corrected turbidity value of bacterial growth on
untreated NB
Ttur is the corrected turbidity value of bacterial growth on
treated NB.
Similarly, the solvent for tomato bacterial wilt was SM
(10.0 g peptone, 5.0 g glucose, 1.0 g casein acid hydroly-
sate, 1000 mL distilled water, pH 7.0 ꢀ7.2), and
thiadiazole copper served as positive control.
(E)-4-(4-((3-nitrobenzylidene)amino)phenoxy)coumarin
(3o). Yellow solid; mp >250°C; yield, 71.5%; IR (KBr):
1718, 1625, 1608, 1185 cmꢀ1 1H NMR (DMSO-d6,
;
500 MHz, ppm) δ 8.90 (s, 1H, CH = N), 8.76 (s, 1H, Ar-
H), 8.40 (d, 2H, J = 9.0 Hz, Ar-H), 8.08 (d, 1H,
J = 8.0 Hz, coumarin-5-H), 7.86 (t, 1H, J = 8.5 Hz, Ar-H),
7.79 (t, 1H, J = 6.5 Hz, Ar-H), 7.54–7.46 ( m, 6H,
coumarin-6,8-H, Ar-H), 5.27 (s, 1H, coumarin-3-H); 13C
NMR (DMSO-d6, 125 MHz, ppm) δ 166.41, 161.68,
160.28, 153.63, 151.14, 149.50, 148.74, 137.94 135.23,
133.98, 131.13, 126.39, 125.09, 123.84, 123.58, 123.39,
122.77, 117.16, 115.32, 93.52; MS (ESI) m/z: 387.1 ([M
+ H]+); Anal. Calcd. for C22H18N2O2: C, 68.39; H, 3.56;
N,7.25. Found: C, 68.11; H, 3.82; N, 7.46.
Acknowledgments. The authors gratefully acknowledge the Science
and Technology Foundation of Guizhou province (No. [2011]
2080), Natural Science Foundation of Guizhou province
education (No. 2010079), and the opening foundation of the Key
Laboratory of Green Pesticide and Agricultural Bioengineering,
Ministry of Education, Guizhou University (No. 2010GDGP0105).
REFERENCES AND NOTES
(E)-4-(4-((4-nitrobenzylidene)amino)phenoxy)coumarin
(3p).
Yellow solid; mp >250°C; yield, 68.2%; IR
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(KBr): 1717, 1627, 1608, 1183 cmꢀ1; H NMR (DMSO-
d6, 500 MHz, ppm) δ 8.90 (s, 1H, CH = N), 8.40 (d, 1H,
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1
Antibacterial biological assay.
The synthesized
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with Tween-20 (0.1%) to prepare different concentrations
of 100 and 200 μg/mL. 1mL of sample liquid was added
to the nontoxic nutrient broth (NB, 1.5 g beef extract,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet