Synthesis and Antimicrobial Activity of Novel 2-Substituted Phenoxy-N-(4-substituted Phenyl-5-(1H-1,2,4-triazol-1-yl)thiazol-2-yl)acetamide Derivatives

Article abstract of DOI:10.1002/jhet.2737

A series of 2-substituted phenoxy-N-(4-substituted phenyl-5-(1H-1,2,4-triazol-1-yl)thiazole-2-yl)acetamide derivatives 8a, 8b, 8c, 8d, 8e, 8f, 8g, 8h, 8i, 8j, 8k, 8l, 8m, 8n, 8o, 8p, 8q, 8r, 8s, 8t was synthesized by the reaction of phenoxyacetyl chloride 7 with intermediate 4-substituted phenyl-5-(1H-1,2,4-triazol-1-yl)thiazol-2-amine 5. Their structures were confirmed by ¹H NMR, ¹³C NMR, MS, IR, and elemental analyses. The synthesized compounds were also screened for their antimicrobial activity against three types of plant fungi (Gibberella zeae, Phytophthora infestans, and Paralepetopsis sasakii) and two kinds of bacteria [Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas axonopodis pv. citri (Xac)] showing promising results. In particular, 8b, 8f, 8g, and 8h exhibited excellent antibacterial activity against Xoo, with 50% effective concentration (EC₅₀) values of 35.2, 80.1, 62.5, and 82.1 μg/mL, respectively, which are superior to the commercial antibacterial agent bismerthiazol (89.9 μg/mL). The preliminary structure–activity relationship studies of these compounds are also briefly described.

Full text of DOI:10.1002/jhet.2737

Month 2016
Synthesis and Antimicrobial Activity of Novel 2-Substituted
Phenoxy-N-(4-substituted Phenyl-5-(1H-1,2,4-triazol-1-yl)thiazol-2-yl)
acetamide Derivatives
*
*
Guo-Ping Liao, Xia Zhou, Wei Xiao, Yan Xie, and Lin-Hong Jin
State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green
Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025
People’s Republic of China
*E-mail: zhouxia_j@126.com; linhong_j@126.com
Additional Supporting Information may be found in the online version of this article.
Received April 13, 2016
DOI 10.1002/jhet.2737
Published online 00 Month 2016 in Wiley Online Library (wileyonlinelibrary.com).
A series of 2-substituted phenoxy-N-(4-substituted phenyl-5-(1H-1,2,4-triazol-1-yl)thiazole-2-yl)acet-
amide derivatives 8a–8t was synthesized by the reaction of phenoxyacetyl chloride 7 with intermediate 4-
substituted phenyl-5-(1H-1,2,4-triazol-1-yl)thiazol-2-amine 5. Their structures were confirmed by 1H
NMR, 13C NMR, MS, IR, and elemental analyses. The synthesized compounds were also screened for their
antimicrobial activity against three types of plant fungi (Gibberella zeae, Phytophthora infestans, and
Paralepetopsis sasakii) and two kinds of bacteria [Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas
axonopodis pv. citri (Xac)] showing promising results. In particular, 8b, 8f, 8g, and 8h exhibited excellent
antibacterial activity against Xoo, with 50% effective concentration (EC50) values of 35.2, 80.1, 62.5, and
82.1 μg/mL, respectively, which are superior to the commercial antibacterial agent bismerthiazol (89.9 μg/
mL). The preliminary structure–activity relationship studies of these compounds are also briefly described.
J. Heterocyclic Chem., 00, 00 (2016).
INTRODUCTION
with yield losses and adverse effects on crop quality.
Derivatives containing thiazole or triazole units can exhibit
a good inhibition for those plant diseases [6,29]. In
addition, incorporation of phenoxyacetamide moiety can
also serve as an effective approach for enhancing antifungal
activity [30]. Fascinated by these investigations, we explored
to develop a practical synthetic route to phenoxyacetamides
bearing both a triazole and a thiazole heterocyclic unit.
Herein, we report the preparation of a series of novel 2-
substituted phenoxy-N-(4-substituted-phenyl-5-(1H-1,2,4-
triazol-1-yl)thiazol-2-yl)acetamide derivatives and the
subsequent evaluation of their biological activity against
plant pathogenic fungi and bacteria.
Thiazole moiety serves as an active core for various
bioactive molecules. Its derivatives have widespread appli-
cation as useful biological agents, such as insecticidal [1],
antibacterial [2–4], antifungal [5,6], herbicidal [7,8], anti-
cancer [9,10], antioxidant [11,12], and anti-inflammatory
[13]. Specifically, a large number of thiazole derivatives,
for example, thiabendazole, ethaboxam, thifluzamide, and
metsulfovax, have already been commercialized as potent
fungicides [14–16]. Therefore, the synthesis of novel
thiazole-incorporated heterocyclic compounds continues
to draw significant interest in scientific community.
On the other hand, 1,2,4-triazole derivatives exhibit
broad-spectrum bioactivity and are widely used in
agrochemicals [17–25] and pharmaceuticals [26–28].
Fungicides containing triazoles, for example, flusilazole,
triadimenol, and propiconazole, are the most effective
plant protection agents against plant pathogens such as
Xanthomonas oryzae pv. oryzae (Xoo) or Gibberella zeae
at present [29].
RESULTS AND DISCUSSION
Synthesis. The synthetic procedure adopted to obtain
the target compounds 8a–8t is shown in Scheme 1. The
intermediate 2-bromo-1-phenylenthanone (2) was
synthesized from acetophenone (1) by reacting with
bromine in liquid phase using aluminum chloride as
catalyst in ice bath [31]. Then, (2) was submitted to
1,2,4-triazole and trimethylamine to obtain the 1-phenyl-
2-(1H-1,2,4-triazol-1-yl)ethanone (3) [32]. The 2-bromo-
1-phenyl-2-bromo-(1H-1,2,4-triazol-1-yl)ethanone (4) can
Plant fungi (G. zeae, Phytophthora infestans, and
Paralepetopsis sasakii) and plant bacteria [Xoo and
Xanthomonas axonopodis pv. citri (Xac)] colonize various
crops that are essential for human nutrition such as wheat,
rice, potato, and citrus. Infected plants are accompanied
© 2016 Wiley Periodicals, Inc.

G.-P. Liao, X. Zhou, W. Xiao, Y. Xie, and L.-H. Jin
Vol 000
Scheme 1. Synthetic route to compounds 8a–8t.
be obtained by bromination of 1-phenyl-2-(1H-1,2,4-
triazol-1-yl)ethanone (3) reacting with liquid bromine
with anhydrous sodium acetate and glacial acetic acid
[33]. The key intermediate 4-phenyl-5-(1H-1,2,4-triazol-
1-yl)thiazol-2-amine (5) was synthesized by 1-phenyl-
2-bromo-(1H-1,2,4-triazol-1-yl)ethanone cyclizing with
thiourea and absolute ethyl alcohol under reflux
condition. The 2-phenoxyacetyl chloride (7) can be
acquired easily from 2-phenoxyacetic acid. The target
compound 2-phenoxyl-N-(4-phenyl-5-(1H-1,2,4-triazol-1-
yl)thiazol-2-yl)acetamide (8) was synthesized by reaction
between 2-phenoxyacetyl chloride (7) dissolved in anhydrous
THF and 4-phenyl-5-(1H-1,2,4-triazol-1-yl)thiazol-2-
amine (5) in the presence of catalyst trimethylamine.
The structure of the title compounds 8a–8t was
confirmed by IR, 1H NMR, 13C NMR, MS, and elemental
analysis. The IR spectrum of 8a–8t displayed the absorp-
tion bands between 3474.2 and 3050.5 cmꢀ1 correspond-
ing to N-H and Ph-H, as well as 1685.4–1650.6 cmꢀ1
of compounds 8a–8t that corresponded well with their
respective molecular formulae.
Antifungal bioactivity.
The antifungal activity of all
synthesized compounds was tested against three
pathogenic fungi, G. zeae, P. infestans, and P. sasakii by
the poison plate technique [34]. All target compounds
were dissolved in DMSO (1 mL) and diluted with sterile
distilled water containing 0.1% Tween-20 (9 mL) to
prepare the 500 μg/mL stock solution before mixing with
molten potato dextrose agar (PDA; 90mL) below 60°C.
The compounds were tested at a concentration of
50 μg/mL for the initial screening. All fungi were poured
into sterilized Petri dishes in PDA at 26.5 0.5°C for
4 days to make new mycelium for antifungal activity test.
Then, mycelia dishes of approximately 4 mm in diameter
were cut from the culture medium. A mycelium was
obtained using a germ-free inoculated plate incubated at
26.5 0.5°C for 4–5 days. DMSO in sterile distilled water
containing 0.1% tween served as a negative control,
whereas hymexazol served as a positive control. Each
treatment condition consisted of three replicates. Radial
growth diameter of the fungal colonies was measured
twice by cross-bracketing method; then, the data were
statistically analyzed. Inhibitory effects of the test
compounds in vitro on these fungi were calculated by the
formula:
1
corresponding to C=O function. The H NMR spectrum
of 8a in DMSO-d6 displayed a singlet at δ 12.92ppm that
corresponds to H–N–C=O functionality, a singlet at δ
8.80 and 8.32 ppm belonged to thiazole ring-CH=N proton,
and the multiplet at δ 7.36–7.31, 7.30–7.27, and 7.01–
6.93ppm that corresponds to phenyl-H functionality. A
singlet that appeared at δ 4.91ppm was observed because
of the protons of CH2 group. The chemical shifts at
168.52 and 66.42ppm in 13C NMR confirmed the
existence of C=O and CH2 groups, respectively. Final
confirmation was obtained from electrospray ionization
(ESI) mass spectra, which exhibited molecular ion peak
Inhibition rate ð%Þ ¼ ½ðCK – TÞ =ðCK – 4 mmÞꢁ ꢂ 100
where CK means the average diameter of fungal growth in
the negative control and T means the average diameter of
fungi on treated PDA.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2016
Synthesis and Antimicrobial Activity of Novel 2-Substituted Phenoxy-N-(4-
substituted Phenyl-5-(1H-1,2,4-triazol-1-yl)thiazol-2-yl)acetamide Derivatives
The inhibitory effects of the synthesized compounds on
the three phytopathogenic fungi were illustrated in Table 1.
The inhibition rates of target compounds 8a–8t against G.
zeae, P. infestans, and P. sasakii displayed the inhibition
rates ranged 12.40–50.53%, 9.11–44.23%, and 0.95–36.28%
at 50 μg/mL, respectively. The inhibition rates of
50 μg/mL of hymexazol on the corresponding fungi were
52.23%, 63.54%, and 52.61%, respectively. The target
products have weak to moderate antifungal activity against
G. zeae. In particular, 8p showed potent antifungal activity
with inhibition rate (50.53%) against G. zeae compared
with hymexazol (52.23%) at 50 μg/mL.
Antibacterial bioactivity. All of the target compounds
were tested for in vitro antibacterial activity against Xoo
and Xac by turbidimeter test [35]. The target compounds
were dissolved in 150 μL of DMSO and diluted with
sterile distilled water containing 0.1% Tween-20 (4 mL)
to prepare 1000 and 500 μg/mL of stock solution. DMSO
in sterile distilled water containing 0.1% Tween-20
served as the negative control. Commercial agricultural
antibacterial bismerthiazol served as a positive control.
Approximately 1 mL of stock solution was added to 4 mL
of nontoxic liquid medium (nutrient broth (NB), 3 g of
beef extract, 5g of peptone, 1g of yeast powder, 10g of
glucose, and 1000mL of distilled water, pH7.0 to 7.2) in
tubes. Then, approximately 40 μL of NB containing Xoo
or Xac was added to 5 mL of solvent NB containing
compounds, DMSO, or bismerthiazol. Then, the
inoculated test tubes were incubated at 30 1°C with
continuous shaking at 180rpm for 24h. The growth of
bacterial culture was monitored with a spectrophotometer
by measuring the optical density at 600nm (OD600). The
inhibitory rate of bacterial culture growth was calculated
using the following equation:
I ð%Þ ¼ ðCK ꢀ TÞ=CKꢂ100
where “CK” implies the value of the corrected optical
density of bacterial growth on untreated NB (negative
control) and “T” means the value of corrected optical
density of bacterial growth on treated NB; “I” denotes the
inhibition rate.
Antibacterial bioassay results indicated that, in
general, most compounds under investigation were
associated with excellent inhibitory effect antibacterial
bioactivities against Xoo and Xac. As shown in
Table 2, almost all of them exhibited excellent antibac-
terial activity against Xoo and Xac at 200 or 100 μg/mL.
In particular, compounds 8b, 8f, 8g, 8h, 8p, and 8q
showed high antibacterial activity against Xoo or Xac
at 200 and 100 μg/mL. Among them, 8b, 8f, 8g, and
8h were highlighted for their significant inhibition
effects with inhibition rates of 90.3–100% at
200 μg/mL and 77.6–98.2% at 100 μg/mL against Xoo,
which were much higher than that of commercial
bactericide bismerthiazol exhibiting the rates of 72.4%
and 54.2%, respectively.
Table 1
Antifungal activities of the title compounds 8a–8t at a concentration of 50 μg/mL.
Average values of inhibition rate (%)a
Compound
R1
R2
G. zeae
P. infestans
P. sasakii
8a
8b
8c
8d
8e
8f
8g
8h
8i
8j
8k
8l
8m
8n
8o
8p
H
H
H
H
H
4-Cl
2,4-di-Cl
4-F
H
4-Cl
2,4-di-Cl
4-F
H
4-Cl
2,4-di-Cl
4-F
H
4-Cl
2,4-di-Cl
4-F
H
4-Cl
30.22 0.85
45.23 0.90
21.19 0.76
35.40 1.11
40.63 1.26
42.65 1.06
42.32 1.17
44.62 0.84
30.66 2.45
40.63 1.39
45.00 1.52
22.52 0.84
12.40 1.84
41.36 0.93
31.09 1.56
50.53 1.72
35.00 1.62
25.63 0.92
40.94 1.89
29.42 0.93
52.23 2.86
15.94 0.85
38.28 1.42
36.57 1.68
23.59 0.91
35.42 1.28
44.23 1.28
40.62 2.54
32.41 0.77
36.45 1.00
33.45 2.08
42.18 0.63
16.46 0.72
21.41 0.54
21.27 1.99
17.50 0.96
36.85 0.60
28.01 0.1
0.95 1.23
30.12 0.59
25.48 2.62
9.58 0.69
29.45 2.78
35.69 2.08
20.50 0.66
36.28 0.98
19.60 0.73
20.06 0.71
20.93 1.32
13.35 1.60
19.63 0.72
16.56 0.90
16.61 0.92
8.53 0.81
31.14 0.92
12.14 0.70
35.89 1.42
7.77 0.95
52.61 4.10
4-OCH3
4-OCH3
4-OCH3
4-OCH3
3,4-di-Cl
3,4-di-Cl
3,4-di-Cl
3,4-di-Cl
4-Cl
4-Cl
4-Cl
4-Cl
4-CH3
4-CH3
4-CH3
4-CH3
8q
8r
8s
8t
15.82 0.62
34.82 0.98
9.11 0.98
2,4-di-Cl
4-F
Hymexazolb
63.54 2.41
aAverage of three replicates.
bThe commercial agricultural fungicide hymexazol was used for comparison of antifungal activity.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

G.-P. Liao, X. Zhou, W. Xiao, Y. Xie, and L.-H. Jin
Vol 000
Table 2
Antibacterial activities of compounds 8a–8t against Xanthomonas oryzae pv. oryzae and Xanthomonas axonopodis pv. citri.
Average values of inhibition rate (%)a
Xanthomonas oryzae pv. oryzae
Xanthomonas axonopodis pv. citri
200 μg/mL 100 μg/mL
Compound
200 μg/mL
100 μg/mL
8a
8b
8c
8d
8e
8f
8g
8h
8i
8j
8k
8l
8m
8n
8o
8p
67.8 1.0
100.0 1.8
23.8 1.2
42.2 0.9
47.3 3.6
95.2 1.5
100.0 3.0
90.3 2.2
75.0 2.0
31.2 1.8
33.9 1.7
35.1 1.5
30.0 1.2
86.8 1.7
37.0 1.5
81.7 1.8
85.5 2.0
12.1 2.2
44.6 1.6
63.4 1.1
72.4 3.1
60.2 1.3
98.2 2.2
11.7 0.8
26.0 0.8
39.2 4.0
78.1 2.1
99.0 1.2
77.6 1.4
67.4 4.1
26.6 1.3
21.3 1.5
28.9 1.1
26.9 1.9
61.3 2.1
28.9 1.1
60.8 1.4
79.0 1.5
9.6 1.9
67.8 2.1
80.2 1.2
42.2 1.7
60.2 1.2
30.4 1.4
80.2 2.1
55.2 2.6
66.1 0.8
40.2 2.1
65.6 2.4
56.8 2.5
28.4 4.2
66.8 2.5
60.2 1.1
40.0 1.1
100.0 1.2
70.1 2.2
30.2 1.2
79.6 2.2
60.0 1.1
77.5 1.4
48.2 1.5
64.1 1.8
20.3 1.1
44.8 1.3
15.1 2.3
57.4 1.6
31.3 3.1
46.8 1.6
21.0 1.6
43.2 1.2
33.6 1.0
16.3 1.2
48.2 3.6
48.2 3.6
27.2 1.4
75.3 2.7
52.8 1.6
23.8 2.2
54.3 1.3
34.2 2.5
50.0 2.2
8q
8r
8s
8t
24.3 1.1
50.8 1.5
54.2 1.2
Bismerthiazolb
aAverage of three replicates.
bThe commercial agricultural antibacterial agent bismerthiazol was used for comparison of antibacterial activity.
Further investigations were conducted with previously
reported compounds possessing excellent activity against
Xoo for their 50% inhibition concentration (EC50) values
(Table 3). EC50 values of compounds 8b, 8f, 8g, and 8h
are 35.2, 80.1, 62.5, and 82.1 μg/mL, respectively, which
appeared to be more potent than the commercial
bactericide bismerthiazol (89.9 μg/mL).
On the basis of the activity values in Table 2, a
preliminary conclusion of the structure–activity relation-
ships could be deduced. Some suitably substituted
monohalogenated and dihalogenated alkoxyphenyl
derivatives (R2 = 4-Cl, 4-F, 2,4-di-Cl) exhibited good
antibacterial activities against Xoo and Xac. For example,
8g, 8f, 8h, 8n, 8q, and 8p displayed higher activity against
Xoo and Xac than those without bearing a similar halogen
substituent; the observed bioactivities of the compounds
followed the order 8b>8g > 8f >8h> 8n> 8q>8p on
Xoo and 8p >8b> 8f >8q> 8h> 8n on Xac (Table 2).
On the other hand, for the same type of R2 substitu-
tions, the substituent effect in the phenyl ring attached
to the thiazole moiety revealed that a methoxy group
at the 4-position of the ring (R1 = 4-OCH3) was supe-
rior to those mono or dichloro substituents at 4-
position or 2,4- position (R1 = 4-Cl or 2,4-di-Cl); the
activity against Xoo for these representative compounds
followed the order 8f, 8g, 8h (R1 = OCH3) >8n, 8o, 8p
(R1 = 4-Cl) > 8i, 8j, 8k (2,4-Cl). In general, it may be
derived that chlorinated alkoxyphenyl derivatives and
4-methoxy group in the aromatic ring attached to thia-
zole exert a significant role in promoting activity. Thus,
compounds 8b, 8g, 8f, and 8h showed potent
antibacterial activities against Xoo and Xac, being
higher than the rest. The effects of electron-withdrawing
substituent chlorine seem more prominent in enhancing
activity.
Table 3
Inhibitory effect of compounds 8b, 8f, 8g, and 8h against Xanthomonas
oryzae pv. oryzae.a
EC50
Compound
(μg/mL)
Toxic regression eq.
R
8b
8f
8g
8h
35.2 5.6
80.1 5.4
62.5 7.8
82.1 4.0
89.9 5.5
y = 2.1427x + 0.8711
y = 1.3583x + 2.4143
y = 1.9088x + 1.572
y = 2.0736x + 1.0295
y = 2.0757x + 0.9445
0.9904
0.9529
0.9824
0.9967
0.9888
Bismerthiazolb
It is worthwhile to note that the intermediate compound
5 incorporating the thiazole moiety showed potent
antibacterial activities (data not given). Nevertheless,
aAverage of three replicates.
bThe commercial agricultural antibacterial agent bismerthiazol was used
for comparison of antibacterial activity.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2016
Synthesis and Antimicrobial Activity of Novel 2-Substituted Phenoxy-N-(4-
substituted Phenyl-5-(1H-1,2,4-triazol-1-yl)thiazol-2-yl)acetamide Derivatives
amidation of intermediate 5 by acyl chloride to generate 7
does not necessarily lead to enhancement of antibacterial
activity. There is no apparent rational for incorporating
phenoxyacetamide [30] as the basis to improve bioactivity.
The antibacterial results showed that the presence of 4-
chloro, 4-fluoroalkoxyphenyl, and 2,4-dichloroalkoxyphenyl
as well as 4-methoxyphenylthiazole units in the target
compound was primarily responsible for increasing
antibacterial activity. The present work demonstrated that
2-substituted phenoxy-N-(4-substituted phenyl-5-(1H-
1,2,4-triazol-1-yl)thiazol-2-yl)acetamide derivatives have
significant potential for developing potent plants
bactericides.
General procedure for synthesis of 4-phenyl-5-(1H-
1,2,4-triazol-1-yl)-2-amine (5a). A mixture of 2-bromo-1-
phenyl-2-(1H-1,2,4-triazol-1-yl)ethanone (5.0 mmol) and
thiourea (7.5 mmol) was refluxed in ethanol for 8 h. The
progress of the reaction was monitored by TLC (mobile
phase, PE :EA = 1:1, vol.); after completion, the solvent
was neutralized with ammonium hydroxide (15%). The
mixture was allowed to stand overnight; the precipitated
solid was filtered, washed with water, and recrystallized
from ethanol to afford compound 5a.
General procedure for synthesis of phenoxyacetyl chloride
(7a). A solution of 2.28 g (1.5 mmol) of phenoxyacetic
acid was dissolved in 10mL of SOCl2, and the catalytic
amounts of DMF were added. The mixture was heated at
reflux for 5h. After completion of the reaction, the excess
thionyl chloride (SOCl2) was removed under vacuum,
and light yellow oil (7) (0.23 g) was obtained by fractional
distillation under reduced pressure with a yield of 90%.
General procedure for synthesis of 2-phenoxy-N-(4-phenyl-
CONCLUSION
In conclusion,
a
series of novel 2-substituted
phenoxy-N-(4-substituted phenyl-5-(1H-1,2,4-triazol-1-yl)
thiazol-2-yl)acetamide derivatives were synthesized and
bioassayed for their antifungal activity against G. zeae, P.
infestans, and P. sasakii and antibacterial activities against
Xoo and Xac in vitro. The study revealed that all of the de-
rivatives exhibited weak to good active against the tested
fungus, with compound 8p showing high antifungal activ-
ity. While most of the compounds demonstrated excellent
inhibitory effects against Xoo and Xac, in particular, com-
pounds 8b, 8f, 8g, and 8h revealed superior activities com-
pared with commercial bactericide bismerthiazol against
Xoo.
5-(1H-1,2,4-triazol-1-yl)thiazol-2-yl)acetamide (8a).
To a
stirred solution of 4-phenyl-5-(1H-1,2,4-triazol-1-yl)-2-
amine (5a) (1 mmol) and triethylamine (1.5 mmol) in dry
THF (15 mL), a solution of phenoxyacetyl chloride
(1.2 mmol) in dry THF (15 mL) was added drop by drop
for 30 min at room temperature. The mixture was stirred
for 6 h. After completion of the reaction, the resultant
triethylamine hydrochloride was filtered, and the filtrate
was evaporated in vacuo to give an oily residue. The
residue was purified by column chromatograph using
PE : EA (5:1) as eluate to afford the target compound 8a.
2-Phenoxy-N-(4-phenyl-5-(1H-1,2,4-triazol-1-yl)thiazol-2-
This work demonstrated that 2-substituted phenoxy-N-
(4-substituted phenyl-5-(1H-1,2,4-triazol-1-yl)thiazol-2-
yl)acetamide derivatives are of great potential for
developing plants bactericides.
yl)acetamide (8a).
A white solid; yield 57.2%; mp
216–218°C; IR (KBr): ν 3475, 3127, 2360,1683, 1533,
1495, 1270, 950, 765, 697 cmꢀ1 1H NMR (500MHz,
;
DMSO-d6): δ 12.91 (s, 1H, NH), 8.79 (s, 1H, 5-Thiazole-H),
8.32 (s, 1H, 3-Thiazole-H), 7.36–7.31 (m, 3H, Ph-H),
7.30–7.27 (m, 2H, Ph-H), 7.25–7.21 (m, 2H, Ph-H),
7.01–6.93 (m, 3H, Ph-H), 4.91 (s, 2H, CH2); 13C NMR
(125 MHz, DMSO-d6): δ 168.52, 158.15, 155.27, 153.68,
148.00, 144.77, 132.36, 130.11, 129.47, 129.32, 127.70,
121.86, 121.18, 115.06, 66.42; MS (ESI, m/z): 400.1 ([M
+ Na]+); Anal. Calcd. for C19H15N5O2S: C, 60.46; H,
4.01; N, 18.56; Found: C, 60.52; H, 4.05; N, 18.23.
EXPERIMENTAL
All of the reagents and solvents were purchased from
Aladdin (Shanghai, China) and used without further
purifications. The melting points of the products were
determined on an XT-4 binocular microscope (Beijing
Tech Instrument Co., Beijing, China). The progress of the
reactions as well as the purity of compounds was
monitored by thin-layer chromatography (TLC) with
GF254 silica-gel precoated sheets using hexane/ethyl
acetate (EA) as eluent; prepared TLC and column
chromatographic purification were performed on silica gel
using petroleum ether (PE)/EA as eluent. The IR spectra
were recorded on FTIR model SHIMADZU-8400S grating
infrared spectrophotometer in KBr pellets. 1H and 13C
NMR (solvent DMSO-d6) spectral analyses were
performed on a JEOL-ECX 500 NMR at room temperature
using TMS as an internal standard.
2-(4-Chlorophenoxy)-N-(4-phenyl-5-(1H-1,2,4-triazol-1-
yl)thiazol-2-yl)acetamide (8b). A white solid; yield 54.6%;
mp 228–230°C, IR (KBr): ν 3474, 3099, 2358, 1685, 1534,
1
1442, 1235, 1069, 950, 689cmꢀ1; H NMR (500MHz,
DMSO-d6): δ 12.92 (s, 1H, NH), 8.80 (s, 1H, 5-Thiazole-H),
8.32 (s, 1H, 3-Thiazole-H), 7.37–7.31 (m, 5H, Ph-H),
7.25–7.20 (m, 2H, Ph-H), 7.02–6.97 (m, 2H, Ph-H), 4.92
(s, 2H, CH2); 13C NMR (125MHz, DMSO-d6): δ 168.25,
157.04, 155.25, 153.70, 148.03, 144.77, 132.33, 129.85,
129.49, 129.34, 127.65, 125.56, 121.18, 116.93, 66.67;
MS (ESI, m/z): 434.1 ([M + Na]+); Anal. Calcd. for
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

G.-P. Liao, X. Zhou, W. Xiao, Y. Xie, and L.-H. Jin
Vol 000
C19H14ClN5O2S: C, 55.41; H, 3.43; N, 17.00; Found: C,
54.87; H, 3.51; N, 17.16.
2-(2,4-Dichlorophenoxy)-N-(4-phenyl-5-(1H-1,2,4-triazol-1-
168.15, 160.14, 157.05, 155.04, 153.68, 148.07, 144.74,
129.84, 129.06, 125.56, 124.77, 119.52, 116.93, 114.75,
66.67, 55.73. MS (ESI, m/z): 464.1 ([M + Na]+); Anal.
Calcd. for C20H16ClN5O3S: C, 54.36; H, 3.65; N, 15.85;
Found: C, 54.21; H, 3.65; N, 15.78.
yl)thiazol-2-yl)acetamide (8c).
A white powder; yield
59.0%; mp 187–189°C; IR (KBr): ν 3384, 3050, 2361,
1
1770, 1537, 1483, 1433, 1288, 1103, 944, 769cmꢀ1; H
2-(2,4-Dichlorophenoxy)-N-(4-(4-methoxyphenyl)-5-(1H-1,2,4-
NMR (500 MHz, DMSO-d6): δ 12.97 (s, 1H, NH), 8.79
(s, 1H, 5-Thiazole-H), 8.32 (s, 1H, 3-Thiazole-H), 7.59
(d, J = 2.8Hz, 1H, Ph-H), 7.39–7.30 (m, 4H, Ph-H),
7.25–7.18 (m, 2H, Ph-H), 7.10 (d, J = 8.8 Hz, 1H, Ph-H),
5.06 (s, 2H, CH2); 13C NMR (125 MHz, DMSO-d6): δ
167.69, 155.31, 153.69, 152.93, 148.41, 144.78, 132.34,
130.02, 129.48, 129.34, 128.61, 127.65, 125.74, 122.95,
115.90, 67.26; MS (ESI, m/z): 469.1 ([M + Na]+); Anal.
Calcd. for C19H13Cl2N5O2S: C, 51.13; H, 2.94; N, 15.69;
Found: C, 51.89; H, 2.88; N, 15.55.
triazol-1-yl)thiazol-2-yl)acetamide (8g).
solid; yield 61.7%; mp 158–160°C; IR (KBr): ν 3440,
A pale yellow
3134, 2934, 1665, 1538,1260, 1175, 1082, 948,
834 cmꢀ1 1H NMR (500MHz, DMSO-d6): δ 12.92
;
(s, 1H, NH), 8.81 (s, 1H, 5-Thiazole-H), 8.34 (s, 1H,
3-Thiazole-H), 7.57 (d, J= 9.6 Hz, 1H, Ph-H), 7.36–7.30
(m, 1H, Ph-H), 7.15 (d, J = 7.7 Hz, 2H, Ph-H), 7.10 (d,
J = 8.8 Hz, 1H, Ph-H), 6.89 (d, J = 8.7 Hz, 2H, Ph-H),
5.06 (s, 2H, CH2), 3.71 (s, 3H, OCH3); 13C NMR
(125 MHz, DMSO-d6): δ 167.56, 160.17, 155.02, 153.69,
152.94, 148.06, 144.75, 130.02, 129.05, 128.60, 125.64,
124.78, 122.85, 119.52, 115.69, 114.76, 67.24, 55.73;
MS (ESI, m/z): 498.1 ([M + Na]+); Anal. Calcd. for
C20H15Cl2N5O3S: C, 50.43; H, 3.17; N, 14.70; Found: C,
51.03; H, 3.21; N, 14.62.
2-(4-Fluorophenoxy)-N-(4-phenyl-5-(1H-1,2,4-triazol-1-yl)
thiazol-2-yl)acetamide (8d). A white solid; yield 50.3%;
mp 199–201°C; IR (KBr): ν 3383, 3121, 2360, 1684,
1
1538, 1503, 1253, 1085, 950, 765, 697cmꢀ1; H NMR
(500 MHz, DMSO-d6): δ 12.92 (s, 1H, NH), 8.79 (s, 1H,
5-Thiazole-H), 8.32 (s, 1H, 3-Thiazole-H), 7.38–7.30 (m,
3H, Ph-H), 7.27–7.20 (m, 2H, Ph-H), 7.16–7.09 (m, 2H,
Ph-H), 7.02–6.95 (m, 2H, Ph-H), 4.91 (s, 2H, CH2); 13C
NMR (125 MHz, DMSO-d6): δ 168.40, 158.39, 156.51,
155.24, 154.51, 153.69, 147.77, 144.74, 132.35, 132.35,
129.48, 129.33, 127.70, 121.20, 116.55, 116.49, 116.35,
67.29; MS (ESI, m/z): 418.1 ([M+ Na]+); Anal. Calcd. for
C19H14FN5O2S: C, 57.71; H, 3.57; N, 17.71; Found: C,
58.23; H, 3.46; N, 17.65.
2-(4-Fluorophenoxy)-N-(4-(4-methoxyphenyl)-5-(1H-1,2,4-
triazol-1-yl)thiazol-2-yl)acetamide (8h).
A yellow solid;
yield 54.3%; mp 229–231°C; IR (KBr): ν 3442, 3127,
2928, 1681, 1541, 1272, 1071, 951, 831, 755cmꢀ1; H
1
NMR (500 MHz, DMSO-d6): δ 12.85 (s, 1H, NH), 8.79
(s, 1H, 5-Thiazole-H), 8.34 (s, 1H, 3-Thiazole-H), 7.15
(d, J =7.9 Hz, 2H, Ph-H), 7.10 (d, J =23.8 Hz, 2H, Ph-H),
6.98 (d, 2H, J= 21.1 Hz, Ph-H), 6.89 (d, J = 7.2Hz, 2H,
Ph-H), 4.88 (s, 2H, CH2), 3.71 (s, 3H, OCH3); 13C NMR
(125 MHz, DMSO-d6): δ 168.34, 160.14, 158.37, 156.52,
155.06, 154.49, 153.68, 148.06, 144.73, 129.07, 124.78,
119.51, 115.45, 114.74, 67.02, 55.72; MS (ESI, m/z):
448.0 ([M + Na]+); Anal. Calcd. for C20H16FN5O3S: C,
56.46; H, 3.76; N, 16.46; Found: C, 56.45; H, 3.76; N,
16.28.
N-(4-(4-Methoxyphenyl)5-(1H-1,2,4-triazol-1-yl)thiazol-2-yl)-
2-phenoxyacetamide (8e). A white solid; yield 55.2%; mp
170–172°C; IR (KBr): ν 3344, 3121, 2365, 1609, 1416,
;
1260, 1176, 1082, 949, 835, 761cmꢀ1 1H NMR
(500 MHz, DMSO-d6): δ 12.87 (s, 1H, NH), 8.79 (s, 1H,
5-Thiazole-H), 8.32 (s, 1H, 3-Thiazole-H), 7.32–7.25 (m,
2H, Ph-H), 7.18–7.14 (m, 2H, Ph-H), 6.98–6.94 (m, 2H,
Ph-H), 6.92–6.87 (m, 2H, Ph-H), 4.90 (s, 2H, CH2), 3.72
(s, 3H, OCH3); 13C NMR (125 MHz, DMSO-d6): δ
168.43, 160.15, 158.15, 155.08, 153.67, 148.06, 144.73,
130.11, 129.07, 124.80, 121.85, 119.51, 115.06, 114.75,
66.41, 55.73; MS (ESI, m/z): 430.1 ([M+ Na]+); Anal.
Calcd. for C20H17N5O3S: C, 58.96; H, 4.21; N, 17.19;
Found: C, 59.06; H, 4.16; N, 17.21.
N-(4-(3,4-Dichlorophenyl)-5-(1H-1,2,4-triazol-1-yl)thiazol-2-
yl)-2-phenoxyacetamide (8i). A yellow solid; yield 57.6%;
mp 192–1194°C; IR (KBr): ν 3393, 3119, 1687, 1695,
1532, 1284, 1241, 949, 769, 673cmꢀ1
;
1H NMR
(500MHz, DMSO-d6): δ 12.97 (s, 1H, NH), 8.86 (s, 1H,
5-Thiazole-H), 8.36 (s, 1H, 3-Thiazole-H), 7.63 (d,
J=8.5Hz, 1H, Ph-H), 7.44 (d, J=2.1Hz, 1H, Ph-H),
7.34–7.23 (m, 2H, Ph-H), 7.10 (s, J=8.5, 1H, Ph-H),
7.00–6.92 (m, 3H, Ph-H), 4.92 (s, 2H, CH2); 13C NMR
(125MHz, DMSO-d6): δ 168.69, 158.12, 155.58, 153.92,
148.06, 142.04, 132.85, 132.08, 131.73, 130.11, 129.55,
127.59, 122.56, 121.89, 115.08, 66.43; MS (ESI, m/z):
468.0 ([M+Na]+); Anal. Calcd. for C19H13Cl2N5O2S: C,
51.13; H, 2.94; N, 15.69; Found: C, 50.66; H, 3.01; N,
15.52.
2-(4-Chlorophenoxy)-N-(4-(4-methoxyphenyl)-5-(1H-1,2,4-
triazol-1-yl)thiazol-2-yl)acetamide (8f).
A yellow solid;
yield 59.3%; mp 236–238°C; IR (KBr): ν 3441, 2932,
2364, 1671, 1541, 1489, 1240, 1175, 1075, 950, 845,
750cmꢀ1 1H NMR (500 MHz, DMSO-d6): δ 12.89
;
(s, 1H, NH), 8.79 (s, 1H, 5-Thiazole-H), 8.32 (s, 1H,
3-Thiazole), 7.33 (d, J= 7.0 Hz, 2H, Ph-H), 7.15 (d,
J =5.9 Hz, 2H, Ph-H), 6.99 (d, J =7.1 Hz, 2H, Ph-H),
6.89 (d, J= 6.8Hz, 2H, Ph-H), 4.91 (s, 2H, CH2), 3.71
(s, 3H, OCH3). 13C NMR (125 MHz, DMSO-d6): δ
2-(4-Chlorophenoxy)-N-(4-(3,4-dichlorophenyl)-5-(1H-1,2,4-
triazol-1-yl)thiazol-2-yl)acetamide (8j). A pale yellow solid;
yield 45.2%; mp 218–220°C; IR (KBr): ν 3409, 3110,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2016
Synthesis and Antimicrobial Activity of Novel 2-Substituted Phenoxy-N-(4-
substituted Phenyl-5-(1H-1,2,4-triazol-1-yl)thiazol-2-yl)acetamide Derivatives
2904, 1680, 1699, 1490, 1243, 1077, 951, 825, 673cmꢀ1
;
2-(4-Chlorophenoxy)-N-(4-(4-chlorophenyl)-5-(1H-1,2,4-
triazol-1-yl)thiazol-2-yl)acetamide (8n).
1H NMR (500MHz, DMSO-d6): δ 12.95 (s, 1H), 8.85 (s,
1H, 5-Thiazole-H), 8.35 (d, 1H, 3-Thiazole-H), 7.63 (d,
J=8.5Hz, 1H, Ph-H), 7.44 (d, J=2.1Hz, 1H, Ph-H),
7.36–7.30 (m, 2H, Ph-H), 7.11 (s, 1H, Ph-H), 7.02–6.97
(m, 2H, Ph-H), 4.91 (s, 2H, CH2); 13C NMR (125MHz,
DMSO-d6): δ 168.51, 157.03, 155.81, 153.89, 148.01,
141.98, 132.86, 132.06, 131.67, 129.81, 129.53, 127.54,
125.57, 122.45, 116.83, 66.78; MS (ESI, m/z): 481.9
([M+H]+); Anal. Calcd. for C19H12Cl3N5O2S: C, 47.47;
H, 2.52; N, 14.57; Found: C, 48.03; H, 2.50; N, 14.64.
2-(2,4-Dichlorophenoxy)-N-(4-(3,4-dichlorophenyl)-5-(1H-
1,2,4-triazol-1-yl)thiazol-2-yl)acetamide (8k). A white solid;
yield 57.3%; mp 212–214°C; IR (KBr): ν 3382, 3026,
1703, 1532, 1480, 1287, 1136, 1075, 945, 875,
A yellow solid;
yield 51.1%; mp 234–1236°C; IR (KBr): ν 3421, 3118,
2925, 1684, 1502, 1285, 1200, 1072, 953, 832, 759cmꢀ1
;
1H NMR (500 MHz, DMSO-d6): δ 12.94 (s, 1H, NH), 8.82
(s, 1H, 5-Thiazole-H), 8.33 (s, 1H, 3-Thiazole-H), 7.48–
7.37 (m, 2H, Ph-H), 7.27–7.18 (m, 2H, Ph-H), 7.17–7.06
(m, 2H, Ph-H), 7.03–6.93 (m, 2H, Ph-H), 4.89 (s, 2H,
CH2); 13C NMR (125 MHz, DMSO-d6): δ 168.50, 158.37,
156.49, 155.39, 154.47, 153.82, 148.00, 143.49, 134.14,
131.20, 129.46, 121.66, 116.52, 116.37, 67.01; MS (ESI, m/
z): 447.8 ([M + H]+). Anal. Calcd. for C19H13Cl2N5O2S: C,
51.13; H, 2.94; N, 15.69; Found: C, 51.46; H, 2.88; N, 15.62.
N-(4-(4-Chlorophenyl)-5-(1H-1,2,4-triazol-1-yl)thiazol-2-yl)-
2-(2,4-dichlorophenoxy)acetamide (8o).
A yellow solid;
786cmꢀ1
;
1H NMR (500MHz, DMSO-d6): δ 13.02
yield 62.5%; mp 215–217°C; IR (KBr): ν 3379, 3102,
(s, 1H, NH), 8.87 (s, 1H, 5-Thiazole-H), 8.36 (s, 1H,
3-Thiazole-H), 7.62 (m, 2H, Ph-H), 7.42 (s, 1H, Ph-H),
7.34 (s, 1H, Ph-H), 7.10 (m, 2H, Ph-H), 5.07 (s, 2H,
CH2); 13C NMR (125MHz, DMSO-d6): δ 167.81,
155.54, 153.93, 152.91, 148.07, 142.06, 132.81, 132.10,
131.75, 130.03, 129.50, 128.60, 127.58, 125.78, 122.97,
122.55, 120.00, 115.72, 67.55; MS (ESI, m/z): 415.9
([M+Na]+); Anal. Calcd. for C19H11Cl4N5O2S: C, 44.29;
H, 2.15; N, 13.59; Found: C, 44.22; H, 2.20; N, 14.06.
N-(4-(3,4-Dichlorophenyl)-5-(1H-1,2,4-triazol-1-yl)thiazole-
2-yl)-2-(4-fluorophenoxy)acetamide (8l). A pale red solid;
yield 58.9%; mp 191–193°C; IR (KBr): ν 3415, 3050,
1696, 1565, 1506, 1278, 1196, 1098, 955, 828,
2906, 1696, 1539, 1484, 1289, 1079, 1001, 945, 840,
773 cmꢀ1 1H NMR (500MHz, DMSO-d6): δ 13.02
;
(s, 1H, NH), 8.82 (s, 1H, 5-Thiazole-H), 8.33 (s, 1H,
3-Thiazole-H), 7.60 (d, J = 2.5 Hz, 1H, Ph-H), 7.43
(d, J = 8.5 Hz, 2H, Ph-H), 7.34 (m, 1H, Ph-H), 7.21
(d, J =8.5 Hz, 2H, Ph-H), 7.09 (d, J = 8.9 Hz, 1H, Ph-H),
5.06 (s, 2H, CH2); 13C NMR (125MHz, DMSO-d6): δ
167.71, 155.35, 153.83, 152.89, 148.02, 143.50, 134.15,
131.17, 130.02, 129.49, 129.42, 128.60, 125.73, 122.91,
121.62, 115.65, 67.63; MS (ESI, m/z): 481.9 ([M + H]+);
Anal. Calcd. for C19H12Cl3N5O2S: C, 47.47; H, 2.52; N,
14.57; Found: C, 47.50; H, 2.52; N, 14.57.
N-(4-(4-Chloropheny)-5-(1H-1,2,4-triazol-1-yl)thiazol-2-yl)-
670cmꢀ1
;
1H NMR (500MHz, DMSO-d6): δ 12.95 (s,
2-(4-fluorophenoxy)acetamide (8p).
A pale yellow solid;
1H, NH), 8.86 (s, 1H, 5-Thiazole-H), 8.36 (s, 1H,
3-Thiazole-H), 7.63 (dd, J=8.4, 2.4Hz, 1H, Ph-H), 7.44
(d, J=1.6Hz, 1H, Ph-H), 7.18–7.07 (m, 3H, Ph-H),
7.04–6.95 (m, 2H, Ph-H), 4.89 (s, 2H, CH2); 13C NMR
yield 61.3%; mp 232–234°C; IR (KBr): ν 3455, 3118,
1
1683, 1539, 1503, 1281, 1201, 1071, 953, 832cmꢀ1; H
NMR (500MHz, DMSO-d6): δ 12.94 (s, 1H, NH), 8.82 (s,
1H, 5-Thiazole-H), 8.33 (s, 1H, 3-Thiazole-H), 7.45–7.39
(m, 2H, Ph-H), 7.26–7.19 (m, 2H, Ph-H), 7.16–7.07 (m,
2H, Ph-H), 7.02–6.94 (m, 2H, Ph-H), 4.89 (s, 2H, CH2);
13C NMR (125MHz, DMSO-d6): δ 168.54, 158.38, 156.50,
155.40, 154.42, 154.42, 147.88, 143.48, 134.15, 131.21,
129.45, 121.77, 116.50, 116.35, 67.81; MS (ESI, m/z):
430.1 ([M +H]+); Anal. Calcd. for C19H13ClFN5O2S: C,
53.09; H, 3.05; N, 16.29; Found: C, 53.21; H, 3.02; N, 16.15.
2-Phenoxy-N-(4-(p-toly)-5-(1H-1,2,4-triazol-1-yl)thiazol-2-
yl)acetamide (8q). A pale yellow solid; yield 66.4%; mp
219–221°C; IR (KBr): ν 3453, 2940, 1676, 1540, 1288,
(125MHz, DMSO-d6):
δ
168.58, 158.40, 156.52,
155.56, 154.47, 153.92, 148.05, 142.03, 132.84, 132.09,
131.72, 129.55, 127.57, 122.57, 116.54, 116.36, 67.30;
MS (ESI, m/z): 464.0 ([M+H]+); Anal. Calcd. for
C19H12Cl2FN5O2S: C, 49.15; H, 2.61; N, 15.08; Found:
C, 49.06; H, 2.68; N, 15.21.
N-(4-(4-Chlorophenyl)-5-(1H-1,2,4-triazol-1-yl)thiazol-2-yl)-
2-phenoxyacetamide (8m). A pale red solid; yield 55.8%;
mp 196–198°C; IR (KBr): ν 3387, 3117, 1681, 1597,
1
1540, 1287, 1233, 1142, 1081, 948, 838, 761 cmꢀ1; H
NMR (500 MHz, DMSO-d6): δ 12.96 (s, 1H, NH), 8.82
(s, 1H, 5-Thiazole-H), 8.33 (s, 1H, 3-Thiazole-H), 7.43
(d, J=8.6Hz, 2H, Ph-H), 7.36–7.26 (m, 2H, Ph-H), 7.22
(d, J=8.6Hz, 2H, Ph-H), 7.01–6.92 (m, 3H, Ph-H), 4.91
(s, 2H, CH2); 13C NMR (125 MHz, DMSO-d6): δ 168.59,
158.12, 155.40, 153.82, 148.01, 143.49, 134.14, 131.21,
130.11, 129.47, 129.45, 121.86, 121.65, 115.05, 66.38;
MS (ESI, m/z): 413.3 ([M + H]+); Anal. Calcd. for
C19H14ClN5O2S: C, 55.41; H, 3.43; N, 17.00; Found: C,
54.25; H, 3.56; N, 17.10.
1081, 949, 824, 759 cmꢀ1 1H NMR (500MHz,
;
DMSO-d6): δ 12.90 (s, 1H, NH), 8.77 (s, 1H, 5-Thiazole-
H), 8.31 (s, 1H, 3-Thiazole-H), 7.32–7.26 (m, 2H, Ph-H),
7.12 (m, 4H, Ph-H), 6.97–6.93 (m, 3H, Ph-H), 4.91 (s,
2H, CH2), 2.25 (s, 3H, CH3); 13C NMR (125MHz,
DMSO-d6): δ 168.47, 158.15, 155.17, 153.64, 148.01,
144.91, 139.09, 130.10, 129.89, 127.58, 121.85, 120.54,
120.00, 115.06, 66.41, 21.33; MS (ESI, m/z): 392.1 ([M
+ H]+); Anal. Calcd. for C20H17N5O2S: C, 61.37; H, 4.38;
N, 17.89; Found: C, 61.40; H, 4.35; N, 17.74.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

G.-P. Liao, X. Zhou, W. Xiao, Y. Xie, and L.-H. Jin
Vol 000
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Chem 1992, 29, 1557.
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2-(4-Chlorophenoxy)-N-(4-(p-toly)-5-(1H-1,2,4-triazol-1-yl)thiazol-
2-yl)acetamide (8r). A red solid; yield 62.1%; mp 242–244°
C; IR (KBr): ν 3441, 2924, 1540, 1490, 1243, 1076, 952, 826,
1
695cmꢀ1; H NMR (500 MHz, DMSO-d6): δ 13.00 (s, 1H,
NH), 8.78 (s, 1H, 5-Thiazole), 8.33 (s, 1H, 3-Thiazole-H),
7.33 (d, J= 8.9Hz, 2H, Ph-H), 7.17–7.08 (m, 4H, Ph-H),
7.03–6.96 (m, 2H, Ph-H), 4.92 (s, 2H, CH2), 2.25 (s, 3H,
CH3); 13C NMR (125 MHz, DMSO-d6): δ 168.19, 157.04,
155.16, 153.63, 148.00, 144.91, 139.08, 129.90, 129.84,
129.58, 127.57, 125.58, 120.56, 117.08, 66.60, 21.31; MS
(ESI, m/z): 426.8 ([M + H]+); Anal. Calcd. for C20H16ClN5O2S:
C, 56.40; H, 3.79; N, 16.44; Found: C, 56.20; H, 3.83; N, 16.40.
2-(2,4-Dichlorophenoxy)-N-(4-(p-toly)-5-(1H-1,2,4-triazol-1-
yl)thiazol-2-yl)acetamide (8s). A pale red solid; yield 64.3%;
mp 215–1217°C; IR (KBr): ν 3380, 3076, 1698, 1536, 1478,
1267, 1103, 943, 826, 768, 650cmꢀ1; 1H NMR (500MHz,
DMSO-d6): δ 12.94 (s, 1H, NH), 8.76 (s, 1H, 5-Thiazole-Hx),
8.31 (s, 1H, 3-Thiazole-H), 7.58 (d, J=1.8Hz, 1H, Ph-H),
7.34 (m, 1H, Ph-H), 7.14 (d, J=8.3Hz, 2H, Ph-H), 7.10
(m, J=8.6, 3H, Ph-H), 5.06 (s, 2H, CH2), 2.24 (s, 3H,
CH3); 13C NMR (125MHz, DMSO-d6): δ 167.58, 155.10,
153.64, 152.94, 148.00, 144.92, 139.10, 130.02, 129.90,
129.57, 128.60, 127.58, 125.76, 122.98, 120.56, 115.72,
67.26, 21.33; MS (ESI, m/z): 460.1 ([M+H]+); Anal.
Calcd. for C20H15Cl2N5O2S: C, 52.18; H, 3.28; N, 15.21;
Found: C, 52.18; H, 3.16; N, 15.32.
2-(4-Fluorophenoxy)-N-(4-(p-toly)-5-(1H-1,2,4-triazol-1-yl)
thiazol-2-yl)acetamide (8t). A pale red solid; yield 57.4%; mp
>250°C; IR (KBr): ν 3431, 3120, 2923, 1672, 1540,
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Fang, J. X.; Liu, J. B. Chin J Org Chem 2013, 33, 1955.
[22] Zhang, S. L.; Chang, J. J.; Damu, G. L. V.; Geng, R. X.;
Zhou, C. H. Med Chem Commun 2013, 4, 839.
[23] Desai, N. C.; Shihora, P. N.; Rajpara, K. M.; Joshi, V. V.;
Vaghani, H. V.; Satodiya, H. M.; Dodiya, A. M. Med Chem Res 2012,
21, 2981.
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Org Chem 2012, 32, 1255.
[25] Shang, J.; Wang, W. M.; Li, Y. H.; Song, H. B.; Li, Z. M.;
Wang, J. G. J Agric Food Chem 2012, 60, 8286.
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2011, 21, 5358.
1
1505, 1200, 1072, 953, 831 cmꢀ1; H NMR (500 MHz,
DMSO-d6): δ 12.90 (s, 1H, NH), 8.78 (s, 1H, 5-Thiazole-H),
8.32 (d, 1H, 3-Thiazole-H), 7.16–7.09 (m, 6H, Ph-H),
7.01–6.93 (m, 2H, Ph-H), 4.87 (s, 2H, CH2), 2.24 (d, 3H,
CH3); 13C NMR (125 MHz, DMSO-d6): δ 168.38, 158.37,
156.49, 155.17, 154.49, 153.66, 148.02, 144.91, 139.10,
129.88, 129.57, 127.58, 120.67, 116.55, 116.52, 116.46,
116.37, 65.90, 19.82; MS (ESI, m/z): 432.1 ([M+ Na]+);
Anal. Calcd. for C20H16FN5O2S: C, 58.67; H, 3.94; N,
17.10; Found: C, 58.44; H, 4.05; N, 17.10.
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H. Arch Pharm Res 2014, 37, 588.
Acknowledgments. This work was supported by the Excellent
Young Science and Technology Talent Cultivation Plan (201122)
and the National Natural Science Foundation “synthesis and
antibacterial activity of novel amide derivatives” (20962005).
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REFERENCES AND NOTES
[1] Dai, H.; Yu, H. B.; Qin, X.; Wang, T. T.; Zhang, X.; Qin, Z. F.;
Fang, J. X. Chin J Org Chem 2013, 33, 1104.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet