Synthesis, characterization and antifungal evaluation of novel 2H-1,4-benzoxazin-3(4H)-one derivatives linked with a 1,2,3-triazole moiety

Article abstract of DOI:10.5560/ZNB.2014-3218

In order to obtain novel bioactive compounds with significant antifungal activities, a series of 2H-1,4-benzoxazin-3(4H)-one analogs linked with a 1,2, 3-triazole moiety have been designed and synthesized via click reactions in a one-pot process at room temperature using CuCl as the catalyst. Their antifungal activities were tested against two plant-pathogenic fungi, Rhizoctonia cerealis (RC) and Colletotrichum capsici (CC). Statistical analysis showed that among the tested compounds in particular compound 3a exhibits a significant growth inhibitory activity against both RC and CC. All the synthesized compounds have been characterized by IR, HRMS and NMR experiments.

Full text of DOI:10.5560/ZNB.2014-3218

Synthesis, Characterization and Antifungal Evaluation of Novel
2H-1,4-Benzoxazin-3(4H)-one Derivatives Linked with a 1,2,3-Triazole
Moiety
Yuqin Jiang, Longfei Mao, Lin Zhu, Baoqi Ren, Wei Li, and Guiqing Xu
College of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, 453007,
P. R. China
Reprint requests to Dr. Wei Li. Fax: +86-373-3329023. E-mail: 031172@htu.cn
Z. Naturforsch. 2014, 69b, 103 – 108 / DOI: 10.5560/ZNB.2014-3218
Received August 2, 2013
In order to obtain novel bioactive compounds with significant antifungal activities, a series of
2H-1,4-benzoxazin-3(4H)-one analogs linked with a 1,2,3-triazole moiety have been designed and
synthesized via click reactions in a one-pot process at room temperature using CuCl as the catalyst.
Their antifungal activities were tested against two plant-pathogenic fungi, Rhizoctonia cerealis (RC)
and Colletotrichum capsici (CC). Statistical analysis showed that among the tested compounds in
particular compound 3a exhibits a significant growth inhibitory activity against both RC and CC. All
the synthesized compounds have been characterized by IR, HRMS and NMR experiments.
Key words: 1,2,3-Triazole, 2H-1,4-Benzoxazin-3(4H)-one, Rhizoctonia Cerealis, Colletotrichum
Capsici
Introduction
HIV [25], anti-convulsant [26], and anti-allergic ef-
fects [27]. As far as we know, the modification
2H-1,4-Benzoxazin-3(4H)-one [1, 2] is an impor- by introducing 1,2,3-triazole groups into 2H-1,4-
tant heterocyclic scaffold. Molecules containing such benzoxazin-3(4H)-one has not been previously re-
a scaffold have been shown to exhibit a range of bio- ported. The main purpose of this work is to synthe-
logical activities [3 – 7]. Among the examples shown size a series of 2H-1,4-benzoxazin-3(4H)-one deriva-
in Fig. 1, compound A exhibits both thrombin in- tives linked with a 1,2,3-triazole moiety. Their antifun-
hibitory and fibrinogen receptor antagonistic activi- gal activities were assessed in vitro against two plant
ties [8]. Compound B is not only a novel antibacterial pathogenic fungi, CC and RC, while the antifungal
and antifungal (anti-candida) agent [9 – 11], but also agent diniconazole was used as a standard.
a potential agent for treating anxiety, depression and
negative symptoms in schizophrenia [12 – 14]. Com- Results and Discussion
pound C and other glycosides with the 2-hydroxy-2H-
1,4-benzoxazin-3(4H)-one skeleton, which are iso-
A one-pot synthesis, to improve the efficiency of
lated from gramineous plants, have been suggested to a chemical reaction, is much desired because time-
act as plant resistance factors against microbial dis- and chemical-consuming separation processes and
eases and insects [15]. Compound D is an inhibitor purification of the intermediates are avoided. The
of bacterial histidine protein kinase [16, 17]. In re- key step for the synthesis of the target molecules
cent years, in order to obtain all kinds of 2H-1,4- is the copper(I)-catalyzed azide-alkyne cycloaddition
benzoxazin-3(4H)-one derivatives, different synthetic (CuAAC) reaction. One aim of this paper is to estab-
methods have been developed [18 – 22].
lish a one-pot reaction of 2H-1,4-benzoxazin-3(4H)-
The 1,4-disubstituted 1,2,3-triazole derivatives have one (1a) [28] or 2H-1,4-benzoxazin-3(4H)-thione
received much attention for their wide range of biolog- (1b) [29], propargyl bromide and substituted phenyl
ical properties including that of a human β3-adrenergic azides [30]. Initially, in order to optimize the reac-
receptor agonist [23], and anti-microbial [24], anti- tion conditions, the reaction of 1a (1 mmol), propar-
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104
Y. Jiang et al. · 2H-1,4-Benzoxazin-3(4H)-one Derivatives
NH
NH2
OH
O
H
N
O
OH
OH
HOOC
O
O
N
O
OH
CH3
A
B
Cl
HO
NH
NH2
O
O
N
O
O
OH
OH
N
H
HO
N
H
O
O
C
D
Fig. 1. Selected biologically important compounds containing a 2H-1,4-benzoxazin-3(4H)-one scaffold.
N
N
N
H
N
CH3COONa
r.
Br
O
N3
mol-%
N
O
O
t.
10
CuCl,
O
2a
1a
Scheme 1. The model reaction for the synthesis of 2a.
Table 1. 2H-1,4-Benzoxazin-3(4H)-one derivatives linked
with a 1,2,3-triazole moiety (2a–g, 3a–e).
gyl bromide (1 mmol) and 1-azido-2-methyl-benzene
(1 mmol) in different co-solvents catalyzed by CuCl
(10 mol-%) in the presence of sodium acetate (1 mmol)
as the base at room temperature was selected as the
model reaction (Scheme 1). Among the tested organic-
water co-solvents, such as ethanol-water, acetone-
water, DMF-water, and 1,4-dioxane-water, the model
reaction in DMF-water (10 mL 1 : 1) showed the best
results, and the yield was 85% in 5 hours. Under the
optimized reaction conditions, triazoles 2a–g and 3a–e
were synthesized using 1a or 1b as the starting mate-
rials as shown in Table 1. All structures of the com-
N
N
N
H
N
N3
X
Br
R
CH3COONa
X
N
O
R
O
10 mol-% CuCl, DMF-H2O, r. t.
1a: X = O
1b: X = S
2a−g:
X = O
3a−e: X = S
Entry
R
Yield (%)
2a
2b
2c
2d
2e
2f
2g
3a
3b
3c
3d
3e
2-CH3
4-OH
2-Cl
3-OH
4-CH3
2-F
3-NO2
2-F
2-CH3
2-Cl
85
86
69
89
89
88
88
82
86
79
81
89
pounds synthesized were confirmed by 1H NMR, 13
NMR, IR, MS, and HR MS experiments.
C
In order to prove the significance of attaching
a 1,2,3-triazole ring at the 2H-1,4-benzoxazin-3(4H)-
one scaffold, compounds 2 and 3 were evaluated for
their in vitro antifungal activities against two plant
pathogenic fungi, CC and RC, taking diniconazole
as the reference drug. Antifungal activity was evalu-
4-CH3
4-Cl
ated by measuring fungal colonies in the presence of results revealed that most of the tested compounds dis-
the tested compounds. This experiment was performed played good inhibitory effects on the growth of the
three times.
tested RC and CC strains. Among all the synthesized
All compounds were tested at a concentration of compounds, compound 3a showed the best antifun-
20 µg mL−1, and the results are shown in Table 2. The gal activities against RC and CC strains with 59%
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Y. Jiang et al. · 2H-1,4-Benzoxazin-3(4H)-one Derivatives
105
Table 2. Antifungal activity of 2H-1,4-benzoxazin-3(4H)-one derivatives, 1a and diniconazole (DCL) at 20 µg mL−1
.
Fungi
Inhibitory ratio (%)
2a
2b
2c
2d
2e
2f
2g
3a
3b
3c
3d
3e
1a
DCL
RC
CC
47.1
50.5
11.8
33.4
5.9
66.7
5.7
35.9
29.4
32.4
0
16.7
41.2
38.3
58.8
68.2
52.9
34.2
54.1
31.6
29.4
66.7
53.7
33.7
13.3
16.2
95.2
98.2
and 68% inhibition, respectively. For CC strains, com- (1 mmol), sodium acetate (1 mmol), substituted phenyl azide
(1 mmol) and cuprous chloride (10 mol-%) were added and
stirred at room temperature. After the reaction was finished
(TLC control), the mixture was poured into water and ex-
tracted with chloroform. The resulting organic phase was
washed with brine, dried over Na2SO4 and evaporated under
reduced pressure. The crude material was then purified by
column chromatography using ethyl acetate-hexane (1 : 15
v/v) as eluent to give the title compounds.
pounds 2c and 3d showed the same fungicidal activ-
ity with inhibition of 67%, a slightly lower value than
that of 3a. Compounds 2b, 2e, 2f, and 3d showed poor
fungicidal activities against the tested fungi (CC, RC)
in vitro, and 2f showed no antifungal activity against
RC.
Compounds 2g, 3b, 3c, and 3e showed better ac-
tivities against RC than CC. Compounds 2c and 3d
showed better activities against CC than RC. All com-
pounds showed better activities against CC strains than
compound 1a, indicating the significance of introduc-
ing a 1,2,3-trizaole moiety into 1a and 1b. It is worth
mentioning that compounds synthesized from 1b ex-
hibit overall better fungicidal activities than the com-
pounds from 1a, which means that the element sulfur
plays a significant role in enhancing the antifungal ac-
tivities of the compounds against the two tested strains.
Based on the results mentioned above, compound 3a
could be taken under consideration for further antifun-
gal research.
Fungicide screening
The tested two plant pathogenic fungi, CC and RC, were
provided by the College of Life Science, Henan Normal Uni-
versity. The fungicidal activity was evaluated in vitro accord-
ing to the literature procedures [31], fungicide diniconazole
being used as a standard.
A stock solution of 200 µg mL−1 of each compound was
prepared using DMSO as a solvent. A working solution
(20 µg mL−1) was prepared by diluting the stock solution
(0.1 mL) with sterilized water (0.9 mL) in a 10 cm diame-
ter Petri dish. Potato dextrose agar (PDA, 9 mL) was then
added to prepare the plate. The plate was swirled to mix the
compound into agar thoroughly under sterilized condition.
After the agar had solidified, a fungi cake of 0.8 mm diame-
ter was inoculated on each plate and cultured in the incubator
at 28 ◦C. After 48 h, the diameter of fungi spread was mea-
sured. Growth inhibition was then calculated using the cor-
responding control. Thein vitro inhibition percentages were
also calculated.
Experimental Section
General Information
All chemicals were obtained from Tianjin Kermel Chem-
ical Reagent Co., Ltd. and were used as received. All melt-
ing points were determined on a Yuhua X-3 melting point
apparatus and are uncorrected. IR spectra were recorded on
a Bio-rad FTS-40 spectrometer. 1H and 13C spectra were
recorded on a Bruker Avance 400 MHz spectrometer oper-
ating at 400.13 and 100.61 MHz, respectively. NMR spectra
were recorded in CDCl3 or [D6]DMSO at room temperature
4-((1-o-Tolyl-1,2,3-triazol-4-yl)methyl)-2H-benzo[b]-
[1,4]oxazin-3(4H)-one (2a)
M. p. 161.1 – 162.4 ◦C. – IR (KBr): ν (cm−1) = 3143,
1609, 1575, 1508, 1479, 1417, 1276, 1236, 1222, 1185,
1124, 1112, 1045, 1035, 1019, 991, 880, 817, 750. – 1H
NMR (400 MHz, CDCl3): δ = 7.79 (s, 1H, CH), 7.61 (d,
J = 7.6 Hz, 1H, Ar-H), 7.39 – 7.27 (m, 4H, Ar-H), 7.09 – 6.97
(m, 3H, Ar-H), 5.28 (s, 2H, CH2), 4.63 (s, 2H, CH2), 2.18
(s, 3H, CH3). – 13C NMR (100 MHz, CDCl3): δ = 164.9,
146.3, 145.2, 136.3, 133.6, 131.5, 129.9, 128.7, 126.8, 125.9,
125.1, 124.3, 123.2, 116.9, 116.1, 67.8, 37.6, 17.9. – MS
((+)-ESI): m/z(%) = 321 (100) [M+H]+. – HRMS ((+)-
1
(20 ± 2 ◦C). H and 13C chemical shifts are quoted in parts
per million downfield from TMS. ESI MS were recorded
on a Bruker Esquire 3000 instrument. High-resolution mass
spectra (HR MS) were obtained from a MicrOTOF-Q II mass
spectrometer with an ESI source (Waters, Manchester, UK).
General procedure for the synthesis of the 1,4-benz-
oxazinon-derived aryl-1,2,3-triazoles (2a–2g and 3a–3e)
In a 50 mL round-bottom flask containing 20 mL of DMF- ESI): m/z = 343.1154 (calcd. 343.1158 for C18H16N4O2,
water (1 : 1 v/v), 1a or 1b (1 mmol), propargyl bromide [M+Na]+).
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106
Y. Jiang et al. · 2H-1,4-Benzoxazin-3(4H)-one Derivatives
4-((1-(4-Hydroxyphenyl)-1,2,3-triazol-4-yl)methyl)-
2H-benzo[b][1,4]oxazin-3(4H)-one (2b)
(400 MHz, CDCl3): δ = 8.00 (s, 1H, CH), 7.60 – 7.56 (m,
3H, Ar-H), 7.29 – 7.26 (m, 2H, Ar-H), 7.08 – 6.97 (m, 3H,
Ar-H), 5.26 (s, 2H, CH2), 4.64 (s, 2H, CH2), 2.40 (s, 3H,
CH3). – 13C NMR (100 MHz, CDCl3): δ = 164.9, 145.1,
143.8, 139.0, 134.6, 130.2, 128.7, 124.3, 123.2, 121.6, 120.4,
116.9, 116.1, 67.8, 37.6, 21.1. – MS ((+)-ESI): m/z(%) =
321 (100) [M+H]+. – HRMS ((+)-ESI): m/z = 343.1171
(calcd. 343.1158 for C18H16N4O2, [M+Na]+).
M. p. 223.2 – 226.4 ◦C. – IR (KBr): ν (cm−1) = 3299,
3134, 2848, 2704, 2599, 2332, 2108, 1877, 1667, 1601,
1521, 1504, 1474, 1417, 1373, 1359, 1322, 1276, 1223,
1127, 1059, 933, 830, 779, 756, 687, 658, 536, 523, 482,
1
453. – H NMR (400 MHz, [D6]DMSO): δ = 9.93 (s, 1H,
OH), 8.52 (s, 1H, CH), 7.62 (d, J = 8.8 Hz, 2H, Ar-H),
7.31 (d, J = 7.2 Hz, 1H, Ar-H), 7.01 – 6.97 (m, 3H, Ar-H),
6.89 (d, J = 8.8 Hz, 2H, Ar-H), 5.20 (s, 2H, CH2), 4.71 (s,
2H, CH2). – 13C NMR (100 MHz, [D6]DMSO): δ = 164.7,
158.2, 145.3, 143.7, 129.1, 128.9, 124.1, 123.1, 122.3, 122.1,
116.9, 116.5, 116.3, 67.6, 36.8. – MS ((+)-ESI): m/z(%) =
323 (100) [M+H]+. – HRMS ((+)-ESI): m/z = 345.0970
(calcd. 345.0974 for C17H14N4O3, [M+Na]+).
4-((1-(2-Fluorophenyl)-1,2,3-triazol-4-yl)methyl)-
2H-benzo[b][1,4]oxazin-3(4H)-one (2f)
M. p. 104.3 – 105.9 ◦C. – IR (KBr): ν (cm−1) = 3143,
1609, 1575, 1508, 1479, 1417, 1276, 1236, 1222, 1185,
1124, 1112, 1045, 1035, 1019, 991, 880, 817, 750. – 1H
NMR (400 MHz, CDCl3): δ = 8.11 (d, J = 2.4 Hz, 1H, CH),
7.92 (t, J = 7.2 Hz, 1H, Ar-H), 7.59 (d, J = 7.2 Hz, 1H, Ar-
H), 7.45 – 7.40 (m, 1H, Ar-H), 7.32 – 7.27 (m, 2H, Ar-H),
7.09 – 6.98 (m, 3H, Ar-H), 5.28 (s, 2H, CH2), 4.64 (s, 2H,
CH2). – 13C NMR (100 MHz, CDCl3): δ = 164.9, 154.5,
152.1, 145.1, 130.4, 130.3, 128.6, 125.2, 125.1, 124.8, 124.3,
123.2, 117.1, 116.9, 115.9, 67.7, 37.4. – MS ((+)-ESI):
m/z(%) = 325 (100) [M+H]+. – HRMS ((+)-ESI): m/z =
347.0914 (calcd. 347.0915 for C17H13FN4O2, [M+Na]+).
4-((1-(2-Chlorophenyl)-1,2,3-triazol-4-yl)methyl)-
2H-benzo[b][1,4]oxazin-3(4H)-one (2c)
M. p. 123.1 – 126.2 ◦C. – IR (KBr): ν (cm−1) = 3148,
3089, 3061, 2919, 2851, 1685, 1604, 1592, 1503, 1468,
1448, 1405, 1375, 1356, 1310, 1284, 1258, 1230, 1128,
1072, 1035, 1017, 989, 932, 879, 769, 747, 695, 685, 553,
534, 485, 463. – 1H NMR (400 MHz, CDCl3): δ = 8.03 (s,
1H, CH), 7.61 – 7.54 (m, 3H, Ar-H), 7.45 – 7.41 (m, 2H, Ar-
H), 7.10 – 6.97 (m, 3H, Ar-H), 5.28 (s, 2H, CH2), 4.62 (s,
2H, CH2). – 13C NMR (100 MHz, CDCl3): δ = 164.9, 145.2,
142.9, 134.8, 130.9, 130.8, 128.7, 128.6, 127.9, 127.7, 125.6,
124.3, 123.2, 116.9, 116.1, 67.8, 37.5. – MS ((+)-ESI):
m/z(%) = 341 (100) [M+H]+. – HRMS ((+)-ESI): m/z =
363.0619 (calcd. 363.0619 for C17H13ClN4O2, [M+Na]+).
4-((1-(3-Nitrophenyl)-1,2,3-triazol-4-yl)methyl)-
2H-benzo[b][1,4]oxazin-3(4H)-one (2g)
M. p. 166.4 – 168.8 ◦C. – IR (KBr): ν (cm−1) = 3158,
3113, 3077, 1682, 1606, 1593, 1539, 1504, 1467, 1398,
1354, 1315, 1280, 1256, 1243, 1127, 1051, 1039, 1021,
1007, 892, 875, 809, 757, 738, 669, 539. – 1H NMR
(400 MHz, CDCl3): δ = 8.58 (t, J = 2.4 Hz, 1H, Ar-H),
8.28 (dd, J1 = 1.20 Hz, J2 = 8.4 Hz, 1H, Ar-H), 8.18 (s, 1H,
CH), 8.13 (dd, J1 = 1.2 Hz, J2 = 8.4 Hz, 1H, Ar-H), 7.73 (t,
J = 8.4 Hz, 1H, Ar-H), 7.53 (dd, J1 = 1.6 Hz, J2 = 7.6 Hz,
1H, Ar-H), 7.08 – 6.98 (m, 3H, Ar-H), 5.78 (s, 2H, CH2),
4.64 (s, 2H, CH2). – 13C NMR (100 MHz, CDCl3): δ =
165.1, 148.9, 145.1, 144.7, 137.6, 131.0, 128.5, 125.9, 124.5,
123.4, 123.3, 121.7, 117.1, 115.8, 115.3, 67.8, 37.4. – MS
((+)-ESI): m/z(%) = 368 (100) [M+H]+. – HRMS ((+)-
ESI): m/z = 374.0864 (calcd. 347.0853 for C17H13N5O5,
[M+Na]+).
4-((1-(3-Hydroxyphenyl)-1,2,3-triazol-4-yl)methyl)-
2H-benzo[b][1,4]oxazin-3(4H)-one (2d)
M. p. 207.5 – 208.1 ◦C. – IR (KBr): ν (cm−1) = 3291,
3157, 2917, 2848, 1661, 1618, 1501, 1473, 1421, 1337,
1282, 1252, 1217, 1175, 1159, 1127, 1058, 1044, 882, 779,
754, 679, 535, 458. – 1H NMR (400 MHz, [D6]DMSO):
δ = 10.01 (s, 1H, OH), 8.64 (s, 1H, CH), 7.35 – 7.25 (m, 4H,
Ar-H), 7.03 – 6.83 (m, 3H, Ar-H), 6.84 (d, J = 8.0 Hz, 1H,
Ar-H), 5.21 (s, 2H, CH2), 4.72 (s, 2H, CH2). – 13C NMR
(100 MHz, [D6]DMSO): δ = 164.7, 158.9, 154.5, 145.4,
143.9, 137.9, 131.2, 128.9, 124.2, 123.2, 122.1, 116.2, 116.1,
110.8, 107.4, 67.6, 36.7. – MS ((+)-ESI): m/z(%) = 323
(100) [M+H]+. – HRMS ((+)-ESI): m/z = 345.0970 (calcd.
345.0974 for C17H14N4O3, [M+Na]+).
4-((1-(2-Fluorophenyl)-1,2,3-triazol-4-yl)methyl)-
2H-benzo[b][1,4]oxazine-3(4H)-thione (3a)
M. p. 70.8 – 72.5 ◦C. – IR (KBr): ν (cm−1) = 3143, 1609,
1575, 1508, 1479, 1417, 1276, 1236, 1222, 1185, 1124,
1112, 1045, 1035, 1019, 991, 880, 817, 750. – 1H NMR
(400 MHz, CDCl3): δ = 8.16 (d, J = 3.2 Hz, 1H, CH), 7.94
(td, J1 = 1.6 Hz, J2 = 7.6 Hz, 1H, Ar-H), 7.43 – 7.38 (m,
4-((1-p-Tolyl-1,2,3-triazol-4-yl)methyl)-
2H-benzo[b][1,4]oxazin-3(4H)-one (2e)
M. p. 147.3 – 148.1 ◦C. – IR (KBr): ν (cm−1) = 3142, 1H, Ar-H), 7.33 – 7.23 (m, 3H, Ar-H), 7.10 – 7.06 (m, 1H,
3085, 2919, 2851, 1682, 1605, 1503, 1471, 1403, 1323, Ar-H), 7.06 – 6.96 (m, 1H, Ar-H), 6.88 (dd, J1 = 1.6 Hz,
1282, 1131, 1057, 886, 815, 760, 537, 521. – 1H NMR J2 = 8.0 Hz, 1H, Ar-H), 4.60 (s, 2H, CH2), 4.50 (s, 2H, CH2).
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Y. Jiang et al. · 2H-1,4-Benzoxazin-3(4H)-one Derivatives
107
–
13C NMR (100 MHz, CDCl3): δ = 160.9, 154.5, 152.0, 4-((1-p-Tolyl-1,2,3-triazol-4-yl)methyl)-
146.2, 144.5, 133.7, 130.2, 130.1, 127.4, 125.7, 125.2, 125.1, 2H-benzo[b][1,4]oxazine-3(4H)-thione (3d)
124.8, 124.4, 124.3, 122.6, 117.1, 115.9, 65.2, 23.5. – MS
M. p. 118.2 – 120.7 ◦C. – IR (KBr): ν (cm−1) = 3112,
3069, 2918, 1696, 1608, 1572, 1518, 1479, 1439, 1340,
1254, 1233, 1124, 1053, 1031, 1014, 989, 932, 876, 847, 816,
756, 739, 604, 531, 459. – 1H NMR (400 MHz, CDCl3): δ =
7.98 (s, 1H, CH), 7.56 (d, J = 8.0 Hz, 2H, Ar-H), 7.33 – 7.27
(m, 3H, Ar-H), 7.10 (t, J = 7.6 Hz, 1H, Ar-H), 7.03 – 6.98
(m, 1H, Ar-H), 6.89 (d, J = 7.6 Hz, 1H, Ar-H), 4.59 (s, 2H,
CH2), 4.52 (s, 2H, CH2), 2.40 (s, 3H, CH3). – 13C NMR
(100 MHz, CDCl3): δ = 161.2, 146.3, 144.8, 138.9, 134.7,
133.8, 130.2, 127.5, 125.7, 122.6, 121.2, 120.5, 115.9, 65.3,
23.6, 21.1. – MS ((+)-ESI): m/z(%) = 337 (100) [M+H]+.
– HRMS ((+)-ESI): m/z = 359.0944 (calcd. 359.0944 for
C18H16N4OS, [M+Na]+).
((+)-ESI): m/z(%) = 341 (100) [M+H]+. – HRMS ((+)-
ESI): m/z = 363.0687 (calcd. 363.0692 for C17H13FN4OS,
[M+Na]+).
4-((1-o-Tolyl-1,2,3-triazol-4-yl)methyl)-
2H-benzo[b][1,4]oxazine-3(4H)-thione (3b)
M. p. 96.1 – 98.7 ◦C. – IR (KBr): ν (cm−1) = 3143, 1609,
1576, 1508, 1479, 1417, 1276, 1236, 1222.5, 1185, 1125,
1112, 1045, 1035, 1019, 991, 880, 817, 750. – 1H NMR
(400 MHz, CDCl3): δ = 7.78 (s, 1H, CH), 7.41 – 7.27 (m,
5H, Ar-H), 7.08 (td, J1 = 1.4 Hz, J2 = 8.0 Hz, 1H, Ar-H),
6.98 (td, J1 = 1.4 Hz, J2 = 8.0 Hz, 1H, Ar-H), 6.88 (dd,
J1 = 1.3 Hz, J2 = 7.9 Hz, 1H, Ar-H), 4.60 (s, 2H, CH2), 4.52
(s, 2H, CH2), 2.17 (s, 3H, CH3). – 13C NMR (100 MHz,
CDCl3): δ = 161.0, 146.3, 144.1, 136.5, 133.8, 133.6, 131.5,
129.8, 127.4, 126.8, 126.0, 125.8, 124.5, 122.5, 115.9, 65.2,
23.6, 17.8. – MS ((+)-ESI): m/z(%) = 337 (100) [M+H]+.
– HRMS ((+)-ESI): m/z = 359.0945 (calcd. 359.0944 for
C18H16N4OS, [M+Na]+).
4-((1-(4-Chlorophenyl)-1,2,3-triazol-4-yl)methyl)-
2H-benzo[b][1,4]oxazine-3(4H)-thione (3e)
M. p. 99.9 – 101.4 ◦C. – IR (KBr): ν (cm−1) = 3124,
3089, 1608, 1575, 1496, 1480, 1424, 1374, 1343, 1246,
1234, 1126, 1074, 1044, 1034, 1015, 988, 940, 878, 842,
765, 748, 724, 691, 613. – 1H NMR (400 MHz, CDCl3):
δ = 8.00 (s, 1H, CH), 7.64 (d, J = 7.6 Hz, 2H, Ar-H), 7.47
(d, J = 7.5 Hz, 2H, Ar-H), 7.31 (d, J = 6.8 Hz, 1H, Ar-H),
7.10 – 6.88 (m, 3H, Ar-H), 4.58 (s, 2H, CH2), 4.52 (s, 2H,
CH2). – 13C NMR (100 MHz, CDCl3): δ = 161.1, 146.3,
145.4, 135.5, 134.6, 133.8, 129.9, 127.6, 125.7, 122.7, 121.7,
121.1, 116.0, 65.2, 23.5. – MS ((+)-ESI): m/z(%) = 357
(100) [M+H]+. – HRMS ((+)-ESI): m/z = 379.0405 (calcd.
379.0389 for C17H13ClN4OS, [M+Na]+).
4-((1-(2-Chlorophenyl)-1,2,3-triazol-4-yl)methyl)-
2H-benzo[b][1,4]oxazine-3(4H)-thione (3c)
M. p. 110.4 – 113.8 ◦C. – IR (KBr): ν (cm−1) = 3143,
1609, 1575, 1508, 1479, 1417, 1276, 1236, 1222, 1185,
1124, 1113, 1045, 1035, 1019, 991, 880, 817, 751. – 1H
NMR (400 MHz, CDCl3): δ = 8.06 (s, 1H, CH), 7.63 – 7.61
(m, 1H, Ar-H), 7.56 – 7.54 (m, 1H, Ar-H), 7.44 – 7.42 (m,
2H, Ar-H), 7.29 (dd, J1 = 2.0 Hz, J2 = 8.0 Hz, 1H, Ar-H),
7.08 (td, J1 = 1.6 Hz, J2 = 8.0 Hz, 1H, Ar-H), 6.99 (td,
J1 = 1.6 Hz, J2 = 8.0 Hz, 1H, Ar-H), 6.88 (dd, J1 = 1.6 Hz,
J2 = 8.0 Hz, 1H, Ar-H), 4.60 (s, 2H, CH2), 4.52 (s, 2H, CH2).
Acknowledgement
The authors would like to thank the Natural Science Foun-
–
13C NMR (100 MHz, CDCl3): δ = 160.9, 146.3, 144.1, dation of China (no. 21172058), the Foundation of the Henan
134.9, 133.8, 130.8, 130.7, 128.4, 127.9, 127.7, 127.4, 125.8, Educational Committee (no. 14A350005), the Scientific Re-
125.2, 122.6, 115.9, 65.2, 23.6. – MS ((+)-ESI): m/z(%) = search Foundation for Doctors (no. 01036500508) and the
357 (100) [M+H]+. – HRMS ((+)-ESI): m/z = 379.0389 Youth Foundation (2012QK11) of Henan Normal University
(calcd. 379.0389 for C17H13ClN4OS, [M+Na]+).
for their financial support.
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