Synthesis and Antibacterial Activity of Novel 1H-indol-2-ol Derivatives

Article abstract of DOI:10.1002/jhet.3043

A series of novel 1H-indol-2-ol derivatives were synthesized and evaluated their antibacterial activities against rice bacterial leaf blight, tobacco bacterial wilt, and citrus canker caused by Xanthomonas oryzae pv. oryzae (Xoo), Ralstonia solanacearum, and Xanthomonas axonopodis pv. citri via the turbidimeter test in vitro. Antibacterial bioassay indicated that most compounds demonstrated good inhibitory effect against Xoo and Ralstonia solanacearum. Especially, compound 4k demonstrated the best inhibitory effect against Xoo with half-maximal effective concentration (EC₅₀) value of 8.27?μg/mL, which was even better than those of commercial agents Bismerthiazol and Thiodiazole copper.

Full text of DOI:10.1002/jhet.3043

Month 2017
Hong Tu,
Synthesis and Antibacterial Activity of Novel 1H-indol-2-ol Derivatives
Shou-Qun Wu, Xiao-Qin Li, Zhen-Chao Wan, Jin-Lin Wan, Kun Tian, and Gui-Ping Ouyang*
Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for Research and
Development of Fine Chemicals, Guizhou University, Guiyang 550025, People’s Republic of China
*
E-mail: tu1990108@163.com
Received April 21, 2017
DOI 10.1002/jhet.3043
Published online 00 Month 2017 in Wiley Online Library (wileyonlinelibrary.com).
A series of novel 1H-indol-2-ol derivatives were synthesized and evaluated their antibacterial activities
against rice bacterial leaf blight, tobacco bacterial wilt, and citrus canker caused by Xanthomonas oryzae
pv. oryzae (Xoo), Ralstonia solanacearum, and Xanthomonas axonopodis pv. citri via the turbidimeter test
in vitro. Antibacterial bioassay indicated that most compounds demonstrated good inhibitory effect against
Xoo and Ralstonia solanacearum. Especially, compound 4k demonstrated the best inhibitory effect against
Xoo with half-maximal effective concentration (EC ) value of 8.27 μg/mL, which was even better than
50
those of commercial agents Bismerthiazol and Thiodiazole copper.
J. Heterocyclic Chem., 00, 00 (2017).
INTRODUCTION
a series of indol derivatives via union of active group
based on the structure–activity relationship, and evaluated
their antibacterial activities. It is believed that these indol
derivatives have a very promising prospect in bactericide.
Indoles are the most ubiquitous components containing
nitrogen heterocycle in nature [1,2]. The indole moiety
remains at the forefront of biological and medicinal
chemistry [3–5]. The most ubiquitous of the bioactive
alkaloids known are based on the indole nucleus. Among
the nitrogen heterocycles, the partially fused acridine
derivatives are important motifs, displaying remarkable
pharmaceutical or biochemical activities, such as antitumor
RESULTS AND DISCUSSION
Chemistry.
The detailed synthetic route for the
preparation of 1H-indol-2-ol derivatives are summarized
in Scheme 1. 2-chloro-1H-indole-3-carbaldehyde (2) [33]
were prepared by indolin-2-one (1) on reaction with
phosphorus oxychloride and DMF. The key intermediate
2-chloro-1-ethyl-1H-indole-3-carbaldehyde (3) [34] was
synthesized from 2-chloro-1H-indole-3-carbaldehyde (2)
reacting with bromoethane in the presence of sodium
carbonate in the acetone. The target compounds (4) were
[
6,7], antifungal, [8] and antibacterial [9]. On the other
hand, the indole moiety has been found in various
pharmacologically and biologically active compounds
[
10,11]. Many indole alkaloids are recognized as one of the
rapidly growing groups of marine invertebrate metabolites
for their broad spectrum of biological properties, such as
anticancer [12], antitumor [13], anti-inflammatory [14],
hypoglycemic, analgesic, and antipyretic [15,16] activities.
Benzopyrrole, a privileged structure, represents a key
motif in heterocyclic chemistry and have shown excellent
performances in antibacterial [17], antiviral [18], antifungal
synthesized
from
2-chloro-1-ethyl-1H-indole-3-
carbaldehyde (3), reacting with different imines and
glacial acetic acid in the ethanol at 80°C. The structures
of the synthesized compounds were confirmed by HRMS,
1
13
[
19], inflammatory [20], antianxiety [21], and
H NMR, C NMR.
antitubercular [22] activities. Meanwhile, alcohol
derivatives are also known to exhibit a wide spectrum
biological activities because the group is an important core
found in many biologically active compounds with a wide
range of biological activity including antibacterial [23],
antifungal [24], insecticidal [25], antiviral [26], herbicidal
The structures of compounds 4a–v were confirmed. The
1
H NMR spectrum of 4d in DMSO-d displayed a singlet
6
at δ 2.54 ppm that corresponds to O = C-CH3
functionality, a singlet at δ 8.66 ppm that corresponds to
ÀN═CH functionality,
a singlet at δ 10.60 that
corresponds to Indol 2-OH. A singlet that appeared at δ
10.87 ppm was observed because of the protons of
benzpyrrole. The structure of 4d was also confirmed by
its mass spectral data. In high resolution mass spectrum,
[
27], anticancer [28], anti-HIV-1 [29], antihepatitis [30],
antitumor [31], and anti-inflammatory [32] properties.
The union of active group is a versatile technology for
searching for new broad-spectrum and high-performance
bactericide. Herein, we attempt to design and synthesize
+
the molecular ion mass Calcd. [M + H] :279.11280
Found:279.11221, corresponding to its molecular weight.
©
2017 Wiley Periodicals, Inc.

H. Tu, S.-Q. Wu, X.-Q. Li, Z.-C. Wan, J.-L. Wan, K. Tian, and G.-P. Ouyang
Vol 000
Scheme 1. Synthetic route to compound 4a–v.
Antibacterial activity of the synthesized compounds.
series of 1H-indol-2-ol derivatives were tested in vitro
antibacterial activity against Xanthomonas oryzae pv.
A
with an inhibition rate of 100% at 200 μg/mL, which was
even better than those of Bismerthiazol (72%) and
Thiodiazole copper (64%). Meanwhile, Table 1 showed
that compounds 4a, 4g, 4i, 4k, 4l, 4n, 4o, and 4s showed
excellent antibacterial activity against R. Solanacearum,
with an inhibition rate of 100% at 200 and 100 μg/mL,
which were better compared with standard drug
Bismerthiazol (50%). And in Table 1 showed that
compounds 4d, 4o, and 4r showed excellent antibacterial
activity against Xac, with an inhibition rate of 100% at
oryzae
solanacearum), and Xanthomonas axonopodis pv. citri
Xac) by the turbidimeter test [25], and the commercial
(Xoo),
Ralstonia
solanacearum
(R.
(
agricultural antibacterial agents Bismerthiazol and
Thiodiazole copper were used as references, as shown in
Table 1, compounds 4a, 4g, 4j–l, 4o, 4q, and 4r
possessed excellent antibacterial activity against Xoo,
Table 1
Antibacterial activity of compounds 7 against Xanthomonas oryzae pv. oryzae, Ralstonia solanacearum, and Xanthomonas axonopodis pv. citri.
a
Inhibition rate (%)
Xanthomomu oryzae pv.oryzae
tobacco bacterial wilt
Xanthomonas axonopodis pv. citri
Compd.
200 mg/L
100 mg/L
200 mg/L
100 mg/L
200 mg/L
100 mg/L
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
s
100 ± 1.32
0
60 ± 2.15
0
100 ± 1.21
70 ± 2.10
39 ± 2.12
100 ± 3.12
90 ± 2.23
100 ± 2.21
100 ± 1.54
100 ± 1.33
100 ± 2.31
14 ± 3.12
100 ± 1.24
100 ± 2.10
90 ± 1.56
100 ± 2.13
100 ± 1.09
100 ± 1.87
80 ± 2.13
100 ± 3.12
100 ± 1.09
50 ± 1.90
70 ± 2.16
0
100 ± 1.32
50 ± 3.10
30 ± 2.16
32 ± 3.15
60 ± 1.09
75 ± 1.45
100 ± 2.12
72 ± 2.44
100 ± 2.43
0
100 ± 1.08
100 ± 3.12
80 ± 2.12
100 ± 1.32
100 ± 2.13
75 ± 2.34
70 ± 2.31
97 ± 1.56
100 ± 2.45
40 ± 3.12
66 ± 2.34
0
0
0
0
0
0
0
60 ± 2.76
63 ± 3.10
70 ± 2.73
60 ± 1.23
100 ± 1.93
63 ± 2.09
64 ± 2.04
100 ± 2.02
100 ± 1.02
100 ± 2.34
81 ± 2.45
0
100 ± 1.98
26 ± 3.24
100 ± 2.09
100 ± 2.43
88 ± 2.93
0
28 ± 2.36
30 ± 2.58
50 ± 2.12
40 ± 3.12
70 ± 2.53
0
100 ± 1.77
65 ± 2.12
36 ± 2.39
51 ± 2.10
0
49 ± 3.09
67 ± 1.45
50 ± 3.03
0
43 ± 2.14
28 ± 1.98
0
50 ± 2.94
0
0
0
93 ± 2.71
100 ± 1.78
95 ± 1.45
37 ± 3.12
0
80 ± 2.31
24 ± 1.23
62 ± 2.41
75 ± 2.12
62 ± 2.10
0
31 ± 2.09
42 ± 1.32
0
0
0
56 ± 2.33
100 ± 2.13
78 ± 2.34
90 ± 1.88
100 ± 2.34
50 ± 2.78
0
50 ± 1.24
24 ± 3.12
62 ± 2.56
63 ± 2.22
53 ± 3.12
43 ± 2.12
0
t
u
v
0
0
0
0
0
0
0
34 ± 2.56
72 ± 0.65
64 ± 2.76
Bismerthiazol
Thiediazole Copper
54 ± 1.23
43 ± 3.15
50 ± 2.11
30 ± 5.41
55 ± 3.41
24 ± 2.35
a
The experiments were repeated three times.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2017
1H-indol-2-ol Derivatives
2
00 μg/mL, which were better compared with standard against Xoo in vitro, with EC50 values of 84.32, 67.56,
drug Thiediazole Copper (55%).
As illustrated in the previous bioassays, the half-
maximal effective concentration (EC ) values of some of
the synthesized compounds as well as for Bismerthiazol
and Thiodiazole copper were presented in Tables 2 and 3.
Table 2 showed that all of the test compounds showed
moderate to excellent activity against Xoo, with EC50
values of 8.27–168.45 μg/mL. Excitingly, compounds 4a,
56.98, 8.27, 50.00, 60.10, 79.42, and 67.03 μg/mL,
respectively, which were even better than that of the
commercial bactericide Bismerthiazol (91.54 μg/mL).
Table 3 showed that all of the test compounds showed
moderate to excellent activity against R. solanacearum,
with EC50 values of 10.25–118.26 μg/mL. Some
compounds showed prominent activity against R.
solanacearum in vitro, which were even better than that
of the commercial bactericide Thiediazole Copper
5
0
4
g, 4j–l, 4o, 4q, and 4r showed prominent activity
(82.17 μg/mL).
Antibacterial activity and the structure–activity
Table 2
relationships.
The 1H-indol-2-ol derivatives that have
Inhibition effect of the compounds against rice bacterial leaf blight.
been synthesized are imines of indol. We speculated that
the additional electron withdrawing group on the benzene
ring in comparison to the benzene ring would contribute
substantially to the antibacterial activity. It was noticeable
that where compounds were active, it was most
commonly against R. solanacearum, and that the
antibacterial activity lacked potency, rarely extending to
the lower rates tested. Although the generally weak
activity makes a detailed analysis of structure activity
relationships difficult, some broad conclusions can be
drawn. The spectrum of antibacterial activity is generally
improved by substituting a halogen group onto the
benzene ring. For example, while compound 4h was
weak active against antibacterial, the equivalent 4k also
displayed activity against Xoo and R. Solanacearum at
Toxic regression
Compd.
EC50(μg/mL)
equation
R
4
4
4
4
4
4
4
4
4
4
4
4
4
4
a
c
d
e
f
g
j
k
l
m
o
q
r
s
84.32 ± 3.83 y = 0.445 × + 12.478 0.99
168.45 ± 1.97 y = 0.335 × À6.434
162.05 ± 2.09 y = 0.363 × À8.826
121.97 ± 5.99 y = 0.293 × +14.260
150.81 ± 0.98 y = 0.207 × +18.782
67.56 ± 5.32 y = 0.408 × +22.434
56.98 ± 4.01 y = 0.974 × À5.501
8.27 ± 2.48 y = 2.465 × +29.608
50.00 ± 3.74 y = 0.920 × +4.023
128.55 ± 3.74 y = 0.440 × À6.565
60.10 ± 0.80 y = 0.757 × +4.506
79.42 ± 2.14 y = 0.554 × +6.054
67.03 ± 3.20 y = 0.731 × +1.088
107.84 ± 5.48 y = 0.485 × À2.304
91.54 ± 2.14 y = 1.499 × +2.051
124.68 ± 3.32 y = 1.540 × +1.790
0.99
0.99
0.97
0.99
0.96
0.99
0.97
0.99
0.99
0.99
0.99
0.99
0.96
0.98
0.98
Bismerthiazol
Thiediazole
Copper
1
00 μg/mL, and 4i was less active against Xoo but was
active against R. Solanacearum, and gave weak activity
against other species. This improvement in activity is not
seen with all derivatives, however. 4k was good active
against Xoo and R. Solanacearum, while 4h was weak
active. 4i was only active against R. Solanacearum. More
generally, it is noticeable that almost all the derivatives of
Compounds with electron donating group on the benzene
ring were weak active, while equivalent derivatives of
compounds with electron withdrawing group were
usually active against R. Solanacearum, and sometimes
display a broader spectrum of activity (e.g., 4a).
EC50, half-maximal effective concentration.
Table 3
Inhibition effect of the compounds against tobacco bacterial wilt.
Toxic regression
Compd.
EC50(μg/mL)
equation
R
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
a
b
e
46.87 ± 3.74 y = 0.960 × +5.033
118.26 ± 4.21 y = 0.375 × +0.565
103.97 ± 5.68 y = 0.470 × +1.913
65.61 ± 3.40 y = 0.777 × À1.023
55.77 ± 2.91 y = 1.022 × À7.105
71.43 ± 2.40 y = 0.791 × À6.502
53.99 ± 3.47 y = 1.065 × À7.504
10.25 ± 2.13 y = 3.088 × +18.304
39.08 ± 5.25 y = 0.882 × +13.523
62.08 ± 3.47 y = 0.814 × À0.534
40.64 ± 3.73 y = 0.880 × +14.23
0.99
0.97
0.96
0.98
0.98
0.99
0.99
0.99
0.99
0.96
0.98
0.98
0.99
0.99
0.99
f
g
h
i
k
l
m
n
o
p
q
r
CONCLUSIONS
A series of indole derivatives containing hydroxy and
imine moieties were synthesized and evaluated their
antibacterial activities against Xoo, R. solanacearum, and
Xac by the turbidimeter test in vitro. The bioassays result
demonstrated that some of the synthesized compounds
exhibited excellent antibacterial activity against Xoo and
R. solanacearum. Among these compounds, compound
4k against Xoo, with EC50 value of 8.27 μg/mL, and
against R. Solanacearum, with EC50 value of 10.25 μg/
mL, which was better than those of Bismerthiazol and
47.44 ± 5.61
y = 0.98 × +3.503
63.23 ± 3.20 y = 0.708 × +5.321
52.84 ± 5.34 y = 0.965 × À1.056
45.55 ± 1.33
y = 0.911 × +8.502
s
78.43 ± 2.57 y = 0.765 × À10.0327 0.99
Thiediazole
Copper
82.17 ± 4.32 y = 0.505 × +8.503 0.98
EC50, half-maximal effective concentration.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

H. Tu, S.-Q. Wu, X.-Q. Li, Z.-C. Wan, J.-L. Wan, K. Tian, and G.-P. Ouyang
Vol 000
Thiediazole copper. This work demonstrated that the
compound 4k can be used to develop potential
bactericides for plants.
149.49, 142.15, 138.05, 137.53, 131.33, 125.29, 124.46,
123.10, 121.05, 118.24, 117.52, 110.52, 109.79, 102.16;
+
HRMS m/z: ([M + H] ); Anal. Calcd. For C H N O :
15 11 3 3
2
82.08732; found 282.08728.
3
-(((2-methoxyphenyl)imino)methyl)-1H-indol-2-ol (4b).
1
EXPERIMENTAL
Yellow solid; yield 62.5%; m.p. 219–220°С; H NMR
(
DMSO-d , 500 MHz) δ: 10.93 (s, 1H, Indol 1-H), 10.46
6
(
s, 1H, Indol 2-OH), 8.63 (s, 1H, ÀN═CH), 7.66 (m, 1H,
General procedure.
Unless otherwise noted, all
Ar-H), 7.59 (m, 1H, Ar-H), 7.10 (m, 1H, Ar-H), 7.05–
6
Ar-H), 3.91 (s, 3H); C NMR (DMSO-d6, 125 MHz) δ:
1
1
1
common reagents and solvents were used as obtained
from commercial supplies without further purifications.
The melting points of the products were determined on a
XT-4 binocular microscope (Beijing Tech Instrument Co.,
.98 (m, 3H, Ar-H), 6.93 (m, 1H, Ar-H), 6.85 (m, 1H,
13
70.38, 147.99, 137.54, 137.36, 129.57, 124.75, 124.53,
1
13
23.63, 121.68, 120.84, 117.58, 113.64, 112.09, 109.66,
China) and were not corrected. H and C NMR (solvent
+
00.62, 56.53; HRMS m/z: ([M + H] ); Anal. Calcd. For
DMSO-d ) spectra were recorded on a JEOL-ECX 500
6
C H O N : 267.11280; found 267.11200.
NMR spectrometer at room temperature using TMS as an
internal standard. HRMS data were measured on Thermo
Scientific Q Exactive (Thermo, Missour, USA). TLC was
performed on silica gel GF254. All anhydrous solvents
were dried and purified according to standard techniques
before use.
16 15 2 2
1
-(3-(((2-hydroxy-1H-indol-3-yl)methylene)amino)phenyl)
ethan-1-one (4c).
2
(
1
7
7
6
1
1
Yellow solid; yield 64.5%; m.p.
1
36–237°С; H NMR (DMSO-d , 500 MHz) δ: 10.81
6
s, 1H, Indol 1-H), 10.54 (s, 1H, Indol 2-OH), 8.67 (s,
H, ÀN═CH), 7.94 (s, 1H, Ar-H), 7.67 (m, 1H, Ar-H),
.65–7.61 (m, 2H, Ar-H), 7.52 (m, 1H, Ar-H),
.05–7.00 (m, 1H, Ar-H), 6.97–6.90 (m, 1H, Ar-H),
General procedure for synthesis of 2-chloro-1H-indole-3-
carbaldehyde (2). Indolin-2-one (6.00 g, 45 mmol) was
added to a solution of POCl (30 mL) dropwise in DMF
13
.86 (m, 1H, Ar-H), 2.63 (s, 3H); C NMR (DMSO-d6,
25 MHz) δ: 198.32, 170.42, 141.04, 138.76, 138.22,
37.71, 130.51, 124.85, 124.65, 123.03, 120.91, 120.89,
3
(
30 mL) at 0°C, then the reaction mixture was stirred to
room temperature. After stirring for 24 h, the mixture
was poured into ice water. The mixture was filtered and
the obtained solids were recrystallized from ethanol to
give 2-chloro-1H-indole-3-carbaldehyde (2).
General procedure for synthesis of 2-chloro-1-ethyl-1H-
indole-3-carbaldehyde (3).
carbaldehyde (2) (5.39 g, 30 mmol) in acetone (30 mL),
was added dropwise bromoethane (3.27 g, 30 mmol) and
added sodium carbonate (3.18 g, 30 mmol), then the
reaction mixture was stirred at room temperature. After
stirring for 2 h, the reaction mixture was evaporated
under the reduced pressure, and subsequently diluted with
water. The mixture was filtered and the obtained solids
were recrystallized from ethanol to give 2-chloro-1-ethyl-
1
(
17.89, 115.93, 109.73, 100.94, 27.53; HRMS m/z:
+
[M + H] ); Anal. Calcd. For C H O N : 279.11280;
17 15 2 2
found 279.11215.
1
-(4-(((2-hydroxy-1H-indol-3-yl)methylene)amino)phenyl)
ethan-1-one (4d).
2
1
Yellow solid; yield 58.2%; m.p.
Put 2-chloro-1H-indole-3-
1
12–214°С; H NMR (DMSO-d , 500 MHz) δ: 10.87 (s,
6
H, Indol 1-H), 10.60 (s, 1H, Indol 2-OH), 8.66 (s, 1H,
ÀN═CH), 7.96 (m, 2H, Ar-H), 7.63 (m, 1H, Ar-H), 7.50
(m, 2H, Ar-H), 7.05 (m, 1H), Ar-H, 6.95 (m, 1H, Ar-H),
13
6
1
1
1
.86 (m, 1H, Ar-H), 2.54 (s, 3H); C NMR (DMSO-d6,
25 MHz) δ: 196.74, 170.40, 144.58, 138.05, 137.10,
31.74, 130.83, 125.38, 124.33, 121.14, 118.21, 115.75,
+
09.87, 102.38, 26.99; HRMS m/z: ([M + H] ); Anal.
Calcd. For C H O N : 279.11280; found 279.11221.
17 15 2 2
1
H-indole-3-carbaldehyde (3).
General procedure for synthesis of 3-(((substituted)imino)
3-((methylimino)methyl)-1H-indol-2-ol (4e).
Yellow
H NMR
1
solid; yield 44.2%; m.p. 201–202°С;
methyl)-1H-indol-2-ol 7a–v. To a solution of 2-chloro-1-
ethyl-1H-indole-3-carbaldehyde (0.42 g, 2 mmol) in
ethanol (20 mL), was added dropwise amine (4 mmol)
and glacial acetic acid (2 mL). After heating and stirring
for 12 h, the mixture was diluted with water and was
filtered and the solid obtained and recrystallized from
ethanol to give compounds 4a–v.
(DMSO-d , 500 MHz) δ: 10.11 (s, 1H, Indol 2-OH), 8.61
6
(s, ÀN═CH), 7.84 (m, 1H, Ar-H), 7.37 (s, 1H, Indol
1-H), 7.25 (m, 1H, Ar-H), 6.94–6.83 (m, 2H, Ar-H), 3.08
13
(s, 3H); C NMR (DMSO-d6, 125 MHz) δ: 170.06,
149.35, 136.05, 125.96, 122.40, 120.23, 115.31, 109.09,
+
94.81, 35.77; HRMS m/z: ([M + H] ); Anal. Calcd. For
C H N O: 175.08659; found 175.08638.
10 10 2
3
-(((3-nitrophenyl)imino)methyl)-1H-indol-2-ol (4a).
3-((ethylimino)methyl)-1H-indol-2-ol (4f). Yellow solid;
1
1
Yellow solid; yield 61.9%; m.p. 247–249°С; H NMR
yield 48.2%; m.p. 86–87°С; H NMR (DMSO-d ,
6
(
(
DMSO-d , 500 MHz) δ: 10.85 (s, 1H, Indol 1-H), 10.55
s, 1H, Indol 2-OH), 8.69 (s, 1H, ÀN═CH), 8.34 (m, 1H,
500 MHz) δ: 10.01 (s, 1H, Indol 2-OH), 8.11 (s, 1H,
ÀN═CH), 7.69 (m, 1H, Ar-H), 7.39–7.26 (m, 3H, Ar-H),
6
13
Ar-H), 7.84 (m, 2H, Ar-H), 7.66–7.60 (m, 2H, Ar-H),
4.37 (d, J = 7.2 Hz, 2H), 1.31 (d, J = 7.2 Hz, 3H);
C
7
.04 (m, 1H, Ar-H), 6.94 (m, 1H, Ar-H), 6.85 (m, 1H,
NMR (DMSO-d6, 125 MHz) δ: 183.82, 136.20, 135.32,
124.41,124.34, 123.82, 120.66, 112.46, 111.39, 39.23,
13
Ar-H); C NMR (DMSO-d6, 125 MHz) δ: 170.28,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2017
1H-indol-2-ol Derivatives
+
1
4.97; HRMS m/z: ([M + H] ); Anal. Calcd. For
3-(((2,4-dimethylphenyl)imino)methyl)-1H-indol-2-ol (4l).
1
C H ON : 189.10224; found 189.10170.
-((isopropylimino)methyl)-1H-indol-2-ol (4g).
solid; yield 38.3%; m.p. 85–86°С; H NMR (DMSO-d ,
00 MHz) δ: 10.19 (s, 1H, Indol 1-H), 10.02 (s, 1H,
Indol 2-OH), 8.11 (s, 1H, ÀN═CH), 7.97 (m, 1H, Ar-H),
.69 (m, 1H, Ar-H), 7.35 (m, 1H, Ar-H), 6.88 (m, 1H,
Ar-H), 3.67 (d, J = 13.2, Hz, 1H), 1.27–1.24 (m, 6H);
C NMR (DMSO-d6, 125 MHz) δ: 183.83, 146.51,
35.33, 124.49, 123.83, 120.66, 120.25, 111.39, 109.14,
Yellow solid; yield 64.5%; m.p. 192–193°С; H NMR
DMSO-d , 500 MHz) δ: 10.92 s, 1H, Indol 1-H), 10.51
11
13
2
3
Yellow
(
6
1
6
(s, 1H, Indol 2-OH), 8.66 (s, 1H, ÀN═CH), 7.84 (m, 1H,
5
Ar-H), 7.59 (m, 1H, Ar-H), 7.50 (m, 1H, Ar-H), 7.18–
13
7
.03 (m, 4H, Ar-H), 2.32–2.26 (m, 6H); C NMR
7
(DMSO-d 125 MHz) δ: 170.76, 159.72, 138.82, 137.28,
6,
1
36.31, 132.03, 128.22, 125.17, 124.72, 124.31, 120.86,
13
117.49, 113.93, 109.72, 100.02, 20.82, 17.43; HRMS
+
1
5
m/z: ([M + H] ); Anal. Calcd. For C H ON :
17
17
2
+
0.01, 23.94; HRMS m/z: ([M + H] ); Anal. Calcd. For
C H ON : 203.11789; found 203.11705.
2
65.13354; found 265.13293.
3-(((2-ethylphenyl)imino)methyl)-1H-indol-2-ol (4m).
12
15
2
1
3
-((p-tolylimino)methyl)-1H-indol-2-ol
(4h).
Yellow
Yellow solid; yield 48.1%; m.p. 181–182°С; H NMR
1
solid; yield 60.8%; m.p. 268–269°С; H NMR (DMSO-
d6, 500 MHz) δ: 10.69 (s, 1H, Indol 1-H), 10.47 (s, 1H,
Indol 2-OH), 8.56 (s, 1H, ÀN═CH), 7.57 (m, 1H, Ar-H),
(DMSO-d , 500 MHz) δ: 11.11 (s, 1H, Indol 1-H), 10.51
6
(s, 1H, Indol 2-OH), 8.70 (s, 1H, ÀN═CH), 7.61 (m, 2H,
Ar-H), 7.33–7.22 (m, 2H, Ar-H), 7.02 (m, 2H, Ar-H),
6.93 (m, 1H, Ar-H), 6.88 (m, 1H, Ar-H), 2.78–2.63 (m,
7
.29 (m, 2H, Ar-H), 7.19 (m, 2H, Ar-H), 6.99 (m, 1H,
13
Ar-H), 6.92 (m, 1H, Ar-H), 6.84 (s, 1H, Ar-H), 2.28 (s,
H); C NMR (DMSO-d 125 MHz) δ: 170.42, 138.71,
38.09, 137.34, 132.71, 130.60, 124.87, 124.34, 120.83,
17.44, 116.37, 109.62, 99.61, 20.86; HRMS m/z:
2H), 1.24 (t, J = 7.5 Hz, 3H); C NMR (DMSO-d6,
125 MHz) δ: 170.80, 138.96, 138.07, 137.40, 131.29,
129.84, 127.84, 124.58, 124.52, 123.67, 120.94, 117.62,
114.45, 109.79, 100.50, 24.21, 14.26; HRMS m/z:
13
3
1
1
6,
+
+
(
[M + H] ); Anal. Calcd. For C H ON : 251.11789;
([M + H] ); Anal. Calcd. For C H ON : 265.13354;
1
6
15
2
17 17
2
found 251.11720.
found 265.13348.
3
-(((4-(trifluoromethyl)phenyl)imino)methyl)-1H-indol-2-ol
3-(((2,6-dimethylphenyl)imino)methyl)-1H-indol-2-ol (4n).
1
1
(4i).
Yellow solid; yield 46.1%; m.p. 228–229°С; H
Yellow solid; yield 44.3%; m.p. 150–151°С; H NMR
NMR (DMSO-d , 500 MHz) δ: 10.83 (s, 1H, Indol 1-H),
6
(DMSO-d , 500 MHz) δ: 10.41 (s, 1H, Indol 1-H), 10.27
6
1
0.59 (s, 1H, Indol 2-OH), 8.65 (s, 1H, ÀN═CH), 8.04
(
1
s, 1H, Indol 2-OH), 8.04 (s, 1H, ÀN═CH), 7.46 (m,
(m, 1H, Ar-H), 7.61 (m, 4H, Ar-H), 7.45 (m, 1H, Ar-H),
H, Ar-H), 7.20–7.14 (m, 3H, Ar-H), 6.96 (m, 1H,
1
3
1
3
6
1
1
.94 (m, 2H, Ar-H); C NMR (DMSO-d 125 MHz) δ:
6,
70.37, 144.04, 138.05, 137.32, 131.28, 127.34, 125.32,
24.39, 121.10, 118.14, 116.46, 115.66, 109.84, 102.19;
Ar-H), 6.88–6.83 (m, 2H, Ar-H), 2.32 (s, 6H); C NMR
DMSO-d6, 125 MHz) δ: 170.57, 146.00, 138.82,
36.95, 132.38, 129.27, 126.34, 125.17, 123.83, 120.66,
(
1
+
+
HRMS m/z: ([M + H] ); Anal. Calcd. For C H ON F :
1
6
12
2
3
116.87, 109.49, 98.11, 18.78; HRMS m/z: ([M + H] );
3
05.08962; found 305.08972.
Anal. Calcd. For C H ON : 265.13354; found
17
17
2
3
-((benzylimino)methyl)-1H-indol-2-ol (4j).
Red solid;
yield 65.3%; m.p. 189–190°С; H NMR (DMSO-d6,
00 MHz) δ: 10.20 (s, 1H, Indol 1-H), 9.07 (s, 1H,
2
65.13354.
1
3-(((4-ethoxyphenyl)imino)methyl)-1H-indol-2-ol (4o).
1
5
Yellow solid; yield 64.5%; m.p. 212–213°С; H NMR
DMSO-d , 500 MHz) δ: 10.67 (s, 1H, Indol 1-H), 10.45
Indol 2-OH), 8.02 (s, 1H, ÀN═CH), 7.37 (m, 4H,
(
6
Ar-H), 7.29 (m, 2H, Ar-H), 6.90 (m, 1H, Ar-H), 6.84
(s, 1H, Indol 2-OH), 8.50 (s, 1H, ÀN═CH), 7.56 (m, 1H,
13
(m, 1H, Ar-H), 6.78 (m, 1H, Ar-H), 4.56 (d, J = 6.4 Hz,
Ar-H), 7.33 (m, 2H, Ar-H), 6.94 (m, 5H, Ar-H), 4.01 (t,
13
2
1
1
H);
C NMR (DMSO-d6, 125 MHz) δ: 170.17,
J = 6.9 Hz, 2H), 1.32 (t, J = 6.9 Hz, 3H); C NMR
48.19, 139.73, 136.35, 129.18, 127.93, 125.72, 122.84,
20.37, 115.66, 109.22, 95.73, 52.11; HRMS m/z:
(DMSO-d 125 MHz) δ: 170.35, 155.36, 139.26, 137.16,
6,
1
33.86, 125.02, 124.06, 120.74, 117.91, 117.23, 115.92,
+
+
([M + H] ); Anal. Calcd. For C H ON : 251.11789;
1
6
15
2
109.55, 98.99, 63.81, 15.24; HRMS m/z: ([M + H] );
found 251.11769.
Anal. Calcd. For C H O N : 281.12845; found
17 17 2 2
3
-(((3-chloro-4-methylphenyl)imino)methyl)-1H-indol-2-ol1
4k). Yellow solid; yield 50.5%; m.p. 246–247°С; H
NMR (DMSO-d , 500 MHz) δ: 10.64 (s, 1H, Indol 1-H),
2
81.12772.
(
3
-(((2,5-dimethoxyphenyl)imino)methyl)-1H-indol-2-ol
1
6
(4p).
Yellow solid; yield 52.2%; m.p. 211–212°С; H
1
2
0.50 (s, 1H, Indol 2-OH), 8.57 (s, ÀN═CH), 7.60 (m,
NMR (DMSO-d , 500 MHz) δ: 10.92 (s, 1H, Indol 1-H),
6
H, Ar-H), 7.32 (m, 1H, Ar-H), 7.25 (m, 1H, Ar-H), 7.01
10.46 (s, 1H, Indol 2-OH), 8.63 (s, 1H, ÀN═CH), 7.62
(m, 1H, Ar-H), 7.29 (m, 1H, Ar-H), 7.08–6.98 (m, 2H,
Ar-H), 6.93 (m, 1H, Ar-H), 6.86 (m, 1H, Ar-H), 6.58 (m,
(m, 1H, Ar-H), 6.93 (m, 1H, Ar-H), 6.83 (m, 1H, Ar-H),
13
2
1
1
1
.28 (s, 3H); C NMR (DMSO-d 125 MHz) δ: 170.33,
6,
13
39.94, 138.15, 137.75,137.66, 132.48, 129.99,
24.75,124.73, 120.93, 117.78, 116.18, 115.64, 109.69,
1H, Ar-H), 3.85 (s, 3H), 3.78 (s, 3H); C NMR (DMSO-
d 125 MHz) δ: 170.37, 154.74, 142.29, 137.62, 137.23,
6,
+
00.71, 19.37; HRMS m/z: ([M + H] ); Anal. Calcd. For
130.32), 124.67, 124.64, 120.82, 117.73, 113.04, 109.69,
C H ON Cl: 285.07892; found 285.07822.
107.52, 100.87, 100.63 (s), 56.97, 56.17; HRMS m/z:
16
14
2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

H. Tu, S.-Q. Wu, X.-Q. Li, Z.-C. Wan, J.-L. Wan, K. Tian, and G.-P. Ouyang
Vol 000
+
+
(
[M + H] ); Anal. Calcd. For C H O N : 297.12337;
HRMS m/z: ([M + H] ); Anal. Calcd. For C H ON Cl:
1
7
17
3
2
15 11
2
found 297.12334.
305.02429; found 305.02390.
3-(((2-ethoxyphenyl)imino)methyl)-1H-indol-2-ol (4v).
Yellow solid; yield 55.9%; m.p. 233–234°С; H NMR
3
-(((3-chlorophenyl)imino)methyl)-1H-indol-2-ol (4q).
1
1
Yellow solid; yield 40.7%; m.p. 204–205°С; H NMR
(
(
(
DMSO-d , 500 MHz) δ: 10.68 (s, 1H, Indol 1-H), 10.53
(DMSO-d , 500 MHz) δ: δ 11.05 (s, 1H, Indol 1-H), 10.39
6
6
s, 1H, Indol 2-OH), 8.60 (s, 1H, ÀN═CH), 7.66–7.57
(s, 1H, Indol 2-OH), 8.63 (s, 1H, ÀN═CH), 7.68–7.56 (m,
2H, Ar-H), 7.08 (m, 1H, Ar-H), 7.01 (m, 3H, A-H), 6.92
(m, 1H, Ar-H), 6.88–6.84 (m, 1H, Ar-H), 4.19–4.10 (m,
m, 2H, Ar-H), 7.38–7.28 (m, 2H, Ar-H), 7.10–7.00 (m,
2
H, Ar-H), 6.94 (m, 1H, Ar-H), 6.86–6.81 (m, 1H, Ar-
13
13
H); C NMR (DMSO-d6, 125 MHz) δ: 170.34, 142.21,
1
2H), 1.42 (m, 3H); C NMR (DMSO-d6, 125 MHz) δ:
37.81, 134.84, 131.67, 124.99, 124.59, 122.97,
170.40, 147.26, 137.55, 137.23, 129.92, 124.98, 124.63,
1
22.86,120.99, 117.95, 115.61, 115.51, 109.74, 101.34;
123.53, 121.74, 120.81, 117.53, 113.43, 113.31, 109.67,
100.55, 64.81, 15.21; HRMS m/z: ([M + H] ); Anal.
+
+
HRMS m/z: ([M + H] ); Anal. Calcd. For C H ON Cl:
1
5
12
2
2
71.06327; found 271.06241.
Calcd. For C H O N : 281.12845; found 281.12775.
17 17 2 2
3
-((m-tolylimino)methyl)-1H-indol-2-ol (4r).
Yellow
Antibacterial activity.
The antibacterial activities of
1
solid; yield 48.0%; m.p. 210–211°С; H NMR (DMSO-d ,
6
some title compounds against Xoo, R. Solanacearum, and
Xac were evaluated by the turbidimeter test.
Dimethylsulfoxide in sterile distilled water served as a
blank control, Bismerthiazol and Thiodiazole copper
served as positive controls. Approximately 40 μL of
solvent M210 (8.0 g of casein enzymatic hydrolysate,
5
2
00 MHz) δ: 10.70 (s, 1H, Indol 1-H), 10.50 (s, 1H, Indol
-OH), 8.60 (s, 1H, ÀN═CH), 7.59 (m, 1H, Ar-H), 7.23
(m, 3H, Ar-H), 7.01 (m, 1H, Ar-H), 6.94–6.83 (m, 3H, Ar-
13
H), 2.33 (s, 3H); C NMR (DMSO-d6, 125 MHz) δ:
1
1
1
70.47, 140.37, 139.76, 138.50, 137.45, 130.04, 124.79,
24.43, 124.41, 120.88, 117.56, 116.76, 113.57, 109.68,
00.03, 21.62; HRMS m/z: ([M + H] ); Anal. Calcd. For
5
.0 g of sucrose, 4.0 g of yeast powder, 3.0 g of
+
K HPO , 0.3 g of MgSO •7H O and 1000 mL of
2
4
4
2
C H ON : 251.11789; found 251.11719.
16
15
2
distilled water; pH
=
7.0) containing Xoo, R.
3
-(((4-hydroxyphenyl)imino)methyl)-1H-indol-2-ol (4s).
1
solanacearum and Xac was added to 5 mL of solvent
M210 containing the test compounds and positive
controls. The inoculated test tubes were incubated at
Yellow solid; yield 62.6%; m.p. 256–257°С; H NMR
DMSO-d , 500 MHz) δ: 10.65 (s, 1H, Indol 1-H),
(
6
1
(
0.42 (s, 1H, Indol 2-OH), 9.34 (s, 1H,Ar-OH), 8.46
s, 1H, ÀN═CH), 7.53 (m, 1H, Ar-H), 7.22 (m, 2H,
Ar-H), 7.01–6.94 (m, 1H, Ar-H), 6.90 (m, 1H, Ar-H),
2
8 ± 1°C and continuously shaken at 180 rpm for 24 h.
The growth of the cultures was monitored on a
microplate reader by measuring the optical density at
13
6
.83 (m, 1H, Ar-H), 6.80–6.77 (m, 2H, Ar-H);
NMR (DMSO-d6, 125 MHz) δ: 170.35, 154.30, 139.50,
37.01, 132.52, 125.09, 123.87, 120.71, 118.11, 117.07,
C
5
95
nm
(OD595
)
given
by
turbiditycorrected
=
ODbacterial wilt À ODno bacterial wilt, and then the
values
1
+
inhibition rate I was calculated by I (%) = (Ctur À Ttur)/
Ctur × 100. Ctur is the corrected turbidity values of
bacterial growth on untreated M210 (blank control), and
Ttur is the corrected turbidity values of bacterial growth
on treated M210. Some of the title compounds tested
against five double declining concentrations method were
expressed by EC50. The average EC50 was computed
from at least three separate analyses for growth inhibition
using the basic EC50 program version SPSS 17.0.
116.62, 109.52, 98.50; HRMS m/z: ([M + H] );
Anal. Calcd. For C H O N : 253.09715; found
2
1
5 13 2 2
53.09729.
3
-(((4-chloro-3-(trifluoromethyl)phenyl)imino)methyl)-1H-
indol-2-ol (4t).
Yellow solid; yield 41.5%; m.p. 252–
1
2
53°С; H NMR (DMSO-d , 500 MHz) δ: 10.76 (s, 1H,
6
Indol 1-H), 10.55 (s, 1H, Indol 2-OH), 8.60 (s, 1H,
ÀN═CH), 7.95 (m, 1H, Ar-H), 7.75–7.60 (m, 3H, Ar-H),
7
.03 (m, 1H, Ar-H), 6.95 (m, 1H, Ar-H), 6.85 (m, 1H,
13
Ar-H); C NMR (DMSO-d6, 125 MHz) δ: 170.20,
1
40.37, 138.06, 137.42, 133.10, 125.27, 124.47, 121.44,
1
21.01, 118.15, 115.84, 109.79, 102.11; HRMS m/z:
Acknowledgment. We gratefully acknowledge the project
enterprises and business (H140192) for providing the financial
support.
+
([M + H] ); Anal. Calcd. ForC H ON ClF : 339.05065;
1
6
11
2
3
found 339.04987.
3
-(((2,5-dichlorophenyl)imino)methyl)-1H-indol-2-ol (4u).
1
Yellow solid; yield 34.0%; m.p. 257–258°С; H NMR
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DMSO-d , 500 MHz) δ: 11.16 (s 1H, Indol 1-H), 10.63
6
(
s, 1H, Indol 2-OH), 8.73 (s, 1H, ÀN═CH), 7.98 (m, 1H,
[
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1H-indol-2-ol Derivatives
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[
SUPPORTING INFORMATION
[
Additional Supporting Information may be found online
in the supporting information tab for this article.
[
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet