Synthesis and biological activities evaluation of new 4-(2,4- difluorophenyl)-N-aryl-5-(1H-1,2,4-triazol-1-yl)thiazol-2-amine

Article abstract of DOI:10.1080/00397911.2010.517609

Fifteen new thiazol-2-amine derivatives containing the 2,4-difluorophenyl unit and 1H-1,2,4-triazole moiety were synthesized. Their structures of all these new compounds have been confirmed by 1H NMR spectra and elemental analysis. The antifungal and plan

Full text of DOI:10.1080/00397911.2010.517609

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Synthesis and Biological Activities
Evaluation of New 4-(2,4-
Difluorophenyl)-N-aryl-5-(1H-1,2,4-
triazol-1-yl)thiazol-2-amine
Jian-Bing Liu a b , Hong Dai b & Jian-Xin Fang b
a College of Chemistry and Chemical Engineering, Hunan Normal
University, Changsha, China
b State Key Laboratory and Institute of Elemento-Organic Chemistry,
NanKai University, Tianjin, China
Published online: 27 Jul 2011.
To cite this article: Jian-Bing Liu , Hong Dai & Jian-Xin Fang (2011): Synthesis and Biological Activities
Evaluation of New 4-(2,4-Difluorophenyl)-N-aryl-5-(1H-1,2,4-triazol-1-yl)thiazol-2-amine, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
41:21, 3197-3206
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Synthetic Communications1, 41: 3197–3206, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.517609
SYNTHESIS AND BIOLOGICAL ACTIVITIES
EVALUATION OF NEW 4-(2,4-DIFLUOROPHENYL)-N-
ARYL-5-(1H-1,2,4-TRIAZOL-1-YL)THIAZOL-2-AMINE
Jian-Bing Liu,1,2 Hong Dai,2 and Jian-Xin Fang2
1College of Chemistry and Chemical Engineering, Hunan Normal University,
Changsha, China
2State Key Laboratory and Institute of Elemento-Organic Chemistry,
NanKai University, Tianjin, China
GRAPHICAL ABSTRACT
Abstract Fifteen new thiazol-2-amine derivatives containing the 2,4-difluorophenyl unit and
1H-1,2,4-triazole moiety were synthesized. Their structures of all these new compounds
have been confirmed by 1H NMR spectra and elemental analysis. The antifungal and
plant-growth-regulatory activities of the title compounds are discussed.
Keywords Antifungal activity; plant-growth-regulatory activity; synthesis; thiazol-2-
amine
Received December 25, 2007.
Address correspondence to Jian-Bing Liu, College of Chemistry and Chemical Engineering, Hunan
Normal University, Lushan Road 36, Changsha, 10081, China. E-mail: liu_jianbing65@yahoo.com.cn
3197

3198
J.-B. LIU, H. DAI, AND X.-J. FANG
INTRODUCTION
2-Aminothiazole derivatives exhibit a wide spectrum of biological activities,
and many of them are well-known antiviral[1] and antifungal agents.[2,3] Some are
used widely as agrochemicals, such as pesticides,[4,5] fungicides,[6,7] and herbicides.[8,9]
In addition, 1H-1,2,4-triazole derivatives not only possess diverse pharmacological
properties, such as antifungal,[10] anti-inflammatory,[11] antiviral,[12] antimicrobial,[13]
antitumorial,[14] anticonvulsant,[15] analgesic,[16] and antihypotensive activities[17]
but also reveal insecticidal, herbicidal, antifungal, and plant-growth-regulatory
activities.[18–20] Biochemists have been paid attention to the study of the biological
activities of 1H-1,2,4-triazole compounds for many years.
Fluorine atoms have many special properties, such as strong electronegativity,
small size, and low polarizability of the C-F bond, and they can have considerable
impact on the behavior of a molecule in a biological environment.[21] Therefore,
fluorinated compounds in general are the focus of much research.[22] In the area
of modern crop protection, fluoro agrochemicals are widely employed as herbicides,
insecticides, and fungicides.[23,24]
Encouraged by these studies, we synthesized fifteen new thiazol-2-amine deri-
vatives using 2-aminothiazole as the parent compound and introducing aryl,
2,4-difluorophenyl, and 1H-1,2,4-triazole-1-yl to the 2, 4, and 5 positions, respect-
ively, (Schemes 1 and 2). The structures have been characterized by 1H NMR spectra
Scheme 1. 5e: R ¼ 4-F; 5f: R ¼ 2-Cl; 5 g: R ¼ 3-Cl; 5 h: R ¼ 4-Cl; 5i: R ¼ 3-Br; 5j: R ¼ 4-Br; 5k: R ¼ 3-CF3;
5 l: R ¼ 4-CF3; 5 m: R ¼ 3-Cl-4-CH3: 5n: R ¼ 2, 4-Cl2; and 5o: R ¼ 2, 5-Cl2.
=
Scheme 2. 5a: R H; 5b: R ¼ 2-CH3; 5c: R ¼ 3-CH3; and 5d: R ¼ 4-CH3.

NEW THIAZOL-2-AMINE DERIVATIVES
3199
and elemental analysis. Preliminary bioassay showed in vitro biological activities and
plant-growth-regulatory activities.
RESULTS AND DISCUSSION
Synthesis
The preferred method for the formation of 2-aminothiazole derivative is the
classical Hantzsch synthesis.[25] Following the Hantzsch protocol, N-monosubsti-
tuted aryl thioureas containing acceptor groups treated with a-mono-bromo ketones
in 1,4-dioxane can form the N-substituted 2-aminothiazole derivative 5e–5o
smoothly (Scheme 1). When the aryl thioureas do not contain acceptor groups, they
could not react with a -mono-bromo ketones to get the corresponding title com-
pound, such as 5a–5d. To our delight, using a,a-dibromo ketones reacted with
N-monosubstituted aryl thioureas in ethanol, title compounds 5a–5d could be
prepared successfully. To the best of our knowledge, the factors affecting Hantzsch
synthesis mainly have electronic and steric effects. The donor electronic effects of the
substituents at the phenyl ring of aryl thioureas depressed its reaction activity of
=
NH2 of aryl thioureas, and it made the reaction of aryl thioureas (R H, CH3) with
a-mono-bromo ketones difficult. As a,a-dibromo ketones possess greater reaction
activity than a-mono-bromo ketones, that make the reaction of a,a-dibromo ketones
with N-monosubstituted aryl thioureas easy. The resolvent is also an important
factor affecting the title reaction. Although the title compounds can be synthesized
using these methods, the yields were not encouraging. The steric and electronic
effects of the bulky group 1H-1,2,4-triazole unit of a-bromo ketones and a,a-
dibromo ketones may be the main factors that affect the yields of this reaction.
Biological Activity
The title compounds 5 were screened for their biological activities in vitro
against the G. zeae, A. solani, C. arachidicola, P. piricola, P. asparagi, C. cucumeri-
num, S. sclerotiorum, and P. oryzae at the concentration of 50 mg=L, and the relative
inhibitory ratios (%) against these fungi are listed in Table 1. As shown in Table 1,
compounds 5h and 5n showed greater fungicidal activities than other title com-
pounds 5. Of all the selected target fungi, compound 5 exhibited the best fungicidal
activity in vitro against C. cucumerinum. Although the screening data revealed that
all selected compounds 5 showed some antifungal activities, they were not significant
compared with known commercial agents. The resolvability and rigidity of the title
molecules may be the main factors that influence the biological activities of the title
compounds. First, these compounds were insoluble in most organic solvents at room
temperature, and this made it difficult to screen the biological activities exactly.
Second, as the 2,4-difluorophenyl unit and 1H-1,2,4-triazole group connect directly
with the 2-aminothiazole cycle, the title molecules were too stiff to contact the target
efficiently. To clarify this further, we modified the molecular structure based on the
title compounds 5, and the study will be presented in forthcoming papers.
The plant-growth-regulatory activities of the title compounds were tested by
the cucumber cotyledon test at the concentration of 10 mg=L. All of the compounds

3200
J.-B. LIU, H. DAI, AND X.-J. FANG
Table 1. Fungicidal activity of the title compounds 5
Relative inhibitory ratio (%)
Compound
G. zeae
A. solani
C. ara.
P. piri.
P. asp.
C. cucu.
S. scler.
P. oryzae
5a
5b
5c
5d
5e
5f
46.7
36.7
23.9
46.9
40.9
55.9
58.6
46.8
57.5
37.8
47.8
43.1
65.0
67.8
47.8
95.6
32.6
37.8
19.7
59.3
59.8
37.6
66.2
75.9
47.9
78.0
39.8
29.8
47.9
56.9
44.3
100
49.1
46.9
37.5
57.3
36.7
21.9
50.5
45.9
26.8
47.5
37.7
46.5
59.2
21.6
33.9
99.5
46.7
54.7
47.6
49.6
38.8
67.8
58.8
79.7
32.2
39.9
47.8
49.6
38.9
69.7
57.1
100
68.9
55.5
19.1
55.0
69.6
25.8
55.5
75.4
37.5
57.1
57.6
39.1
57.0
79.8
66.3
100
69.3
57.9
23.0
67.2
60.7
56.7
68.1
69.5
87.6
65.8
76.7
33.0
78.7
67.9
56.0
99.8
78.8
58.2
65.3
76.9
59.7
66.8
64.9
55.8
55.3
57.2
60.0
65.8
69.5
79.5
52.9
100
27.9
66.4
78.6
34.1
49.9
46.7
65.5
67.3
76.8
59.9
59.9
78.6
45.8
78.5
58.7
100
5g
5h
5i
5j
5k
5l
5m
5n
5o
a
aTriadimenol, 1-(4-chlorophenoxy)-3,3-dimethyl-1-(1H-1, 2,4-triazol-1-yl)butan-2-ol.
exhibited some activities on the growth of cucumber cotylendon, and the inhibitory
ratio is 1.3–50.0%.
SUMMARY
In this study, 15 new thiazol-2-amine derivatives containing the 2,4-difluoro-
phenyl unit and 1H-1,2,4-triazole moiety were synthesized using the Hantzsch
method. Replacement of a-mono-bromo ketones by a,a-dibromo ketones in the
Table 2. Plant-growth-regulatory activities of the title
compounds (%) (10 mg=L)
Compound
Ratio
5a
5b
5c
5d
5e
5f
18.8
8.3
1.3
16.5
10.4
16.5
7.3
5g
5h
5i
4.2
7.8
5j
47.2
22.6
50
5k
5l
5m
5n
5o
7.9
22.6
13.4

NEW THIAZOL-2-AMINE DERIVATIVES
3201
Hantzsch reaction was reported, and this method maybe useful for the synthesis of
thiazol-2-amine derivatives, which contain the bulky group in the 5 position of
thiazol-2-amine derivatives. The results of the bioassay showed that some title com-
pounds exhibited some degree of antifungal and plant-growth-regulatory activities.
EXPERIMENTAL
Instruments
1
All reactions were monitored by thin-layer chromatography (TLC). The H
NMR spectra were measured on a Bruker AC 200, using tetramethylsilane (TMS)
as internal standard and dimethylsulfoxide (DMSO-d6) and CDCl3 as solvent.
Chemical shift values (d) are given in parts per million (ppm). Elemental analyses
were determined with a Yanaco CHN Corder MT-3 elemental analyzer. Melting
points were determined with X-4 digital melting-point apparatus, and the thermo-
meter was uncorrected.
Synthesis of Intermediates 1, 2, 3, and 4
The intermediates 1 and 2 were synthesized according to the literature
method.[26] The intermediates 4 were prepared according to Ref.[27]
Synthesis of 2-Bromo-1-(2,4-difluorophenyl)-2-
(1H-1,2,4-triazol-1-yl)ethanone (3-1)
A solution of 8.8 g (0.055 mol) bromine in acetic acid (20 mL) to a stirred sol-
ution of the intermediate 2 (11.15 g, 0.05 mol) in acetic acid (100 mL), was added
dropwise in 2 h at room temperature. The mixtures were stirred in another 2 h at
room temperature, and then 500 mL ice water was added to the mixtures. After
1 h, the solution was filtered, and the solid obtained was recrystallized from
1
ethanol=water to give a white solid with yield of 69%, mp, 72–74 ꢀC. H NMR
(CDCl3=TMS, 200 MHz): d 9.07 (s, 1H, TrH), 9.16 (s, 1H, TrH), 8.08–8.16 (m,
1H, PhH), 7.67 (d, J ¼ 2.1 Hz, 1H, CH), 7.07–7.13 (m, 1H, PhH), 6.96–7.03 (m,
1H, PhH). Anal. calcd. for C10H6BrF2N3O: C, 39.76; H, 2.00; N, 13.99. Found:
C, 39.58; H, 2.25; N, 14.17.
Synthesis of 2, 2-Dibromo-1-(2,4-difluorophenyl)-2-
(1H-1,2,4-triazol-1-yl)ethanone (3-2)
This product can be obtained by the previous method. The dosages of the sub-
stances were the same as before, except the molar quantity of the bromine was
0.11 mol. Yield: 51.2%, mp 90–92 ꢀC. 1H NMR (CDCl3=TMS, 200 MHz): d
8.00–8.07 (m, 1H, PhH), 7.93 (s, 1H, TrH), 7.56 (s, 1H, TrH), 7.02–7.08 (m, 1H,
PhH), 6.83–6.90 (m, 1H, PhH). Anal. calcd. for C10H5Br2F2N3O: C, 31.53; H,
1.32; N, 11.03. Found: C, 31.45; H, 2.41; N, 11.19.

3202
J.-B. LIU, H. DAI, AND X.-J. FANG
General Procedure for the Preparation of Title Compounds 5e–5o
Intermediate (3-1) (1.51 g, 0.005 mol), 0.06 mol of compound 4, and 20 mL of
1,4-dioxane were added into a 100-mL, four-necked, round-bottomed flask. The
mixture was refluxed for 5–8 h (monitored by TLC). After the solution was cooled
to room temperature, it was poured into a beaker containing 50 mL water at
50–60 ꢀC. The solution was filtered, and the solid was recrystallized from ethanol
to give white solid 5e–5o in various yields.
Selected Data
4-(2, 4-Difluorophenyl)-N-(4-fluorophenyl)-5-(1H-1,2,4-triazol-1-yl)thiazol-2-
amine (5e). White solid; yield: 39.6%; mp 178–180 ꢀC. 1H NMR (DMSO-d6=TMS):
d 10.17 (s, 1H, NH), 8.52 (s, 1H, TrH), 7.99 (s, 1H, TrH), 7.70 (d, d, J ¼ 8.7 Hz, 1H,
PhH), 7.20–7.26 (m, 2H, PhH), 7.01 (d, J ¼ 8.1 Hz, 4H, PhH). Anal. calcd. for
C17H10F3N5S: C, 54.69; H, 2.70; N, 18.76. Found: C, 54.91; H, 2.56; N, 18.98.
4-(2, 4-Difluorophenyl)-N-(2-chlorophenyl)-5-(1H-1,2,4-triazol-1-yl)thiazol-
1
2-amine (5f). White solid; yield: 35.4%; mp 172–174 ꢀC. H NMR (DMSO-d6=
TMS): d 10.11 (s, 1H, NH), 8.70 (s, 1H, TrH), 8.26–8.29 (m, 1H, PhH), 8.20 (s,
1H, TrH), 7.58–7.63 (m, 1H, PhH), 7.51–7.56 (m, 1H, PhH), 7.33–7.39 (m, 1H,
PhH), 7.25–7.29 (m, 1H, PhH), 7.15–7.20 (m, 1H, PhH), 7.10–7.12 (m, 1H, PhH).
Anal. calcd. for C17H10ClF2N5S: C, 52.38; H, 2.59; N, 17.97. Found: C, 52.14; H,
2.56; N, 18.16.
4-(2,4-Difluorophenyl)-N-(3-chlorophenyl)-5-(1H-1,2,4-triazol-1-yl)thiazol-
1
2-amine (5g). White solid; yield: 37.9%; mp 236–239 ꢀC. H NMR (DMSO-d6=
TMS): d 10.80 (s, 1H, NH), 8.71 (s, 1H, TrH), 8.22 (s, 1H, TrH), 7.86 (t, J ¼ 1.8 Hz,
1H, PhH), 7.61 (d, d, J ¼ 8.4 Hz, 1H, PhH), 7.53 (d, d, J ¼ 1.2 Hz, 1H, PhH), 7.39 (d,
J ¼ 8.1 Hz, 1H, PhH), 7.17–7.35 (m, 2H, PhH), 7.07 (d, d, J ¼ 1.2 Hz, 1H, PhH).
Anal. calcd. for C17H10ClF2N5S: C, 52.38; H, 2.59; N, 17.97. Found: C, 52.25; H,
2.45; N, 18.18.
4-(2,4-Difluorophenyl)-N-(4-chlorophenyl)-5-(1H-1,2,4-triazol-1-yl)thiazol-
1
2-amine (5h). White solid; yield: 36.1%; mp 239–241 ꢀC. H NMR (DMSO-d6=
TMS): d 10.21 (s, 1H, NH), 8.68 (s, 1H, TrH), 8.18 (s, 1H, TrH), 7.78 (d, d,
J ¼ 8.7 Hz, 1H, PhH), 7.32–7.38 (m, 2H, PhH), 7.21 (d, J ¼ 8.1 Hz, 2H, PhH), 7.15
(d, J ¼ 7.8, Hz, 2H, PhH). Anal. calcd. for C17H10ClF2N5S: C, 52.38; H, 2.59; N,
17.97; Found: C, 52.16; H, 2.33; N, 18.09.
4-(2,4-Difluorophenyl)-N-(3-bromophenyl)-5-(1H-1,2,4-triazol-1-yl)thiazol-
2-amine (5i). White solid; yield: 31.5%; mp 236–238 ꢀC. 1H NMR (DMSO-d6=
TMS): d 10.78 (s, 1H, NH), 8.71 (s, 1H, TrH), 8.21 (s, 1H, TrH), 7.98 (s, 1H,
PhH), 7.56–7.64 (m, 2H, PhH), 7.29–7.34(m, 2H, PhH), 7.18–7.26 (m, 2H, PhH).
Anal. calcd. for C17H10BrF2N5S: C, 47.02; H, 2.32; N, 16.13. Found: C, 46.86; H,
2.33; N, 16.31.
4-(2,4-Difluorophenyl)-N-(4-bromophenyl)-5-(1H-1,2,4-triazol-1-yl)thiazol-
2-amine (5j). White solid; yield: 33.6%; mp 234–236 ꢀC. 1H NMR (DMSO-d6=
TMS): d 10.73 (s, 1H, NH), 8.69 (s, 1H, TrH), 8.20 (s, 1H, TrH), 7.59–7.67 (m,

NEW THIAZOL-2-AMINE DERIVATIVES
3203
3H, PhH), 7.52 (d, J ¼ 9 Hz, 1H, PhH), 7.16–7.31(m, 2H, PhH). Anal. calcd. for
C17H10BrF2N5S: C, 47.02; H, 2.32; N, 16.13. Found: C, 46.79; H, 2.11; N, 16.40.
4-(2,4-Difluorophenyl)-N-(2-(trifluoromethyl)phenyl)-5-(1H-1,2,4-triazol-
1
1-yl)thiazol-2-amine (5k). White solid; yield: 41.6%; mp 219–221 ꢀC. H NMR
(DMSO-d6=TMS): d 10.94 (s, 1H, NH), 8.72 (s, 1H, TrH), 8.22 (s, 1H, TrH), 8.17
(s, 1H, PhH), 7.86 (d, J ¼ 8.7 Hz, 1H, PhH), 7.55–7.64 (m, 2H, PhH), 7.35 (d,
J ¼ 8.1 Hz, 1H, PhH), 7.17–7.30 (m, 2H, PhH). Anal. calcd. for C18H10BrF5N5S:
C, 51.07; H, 2.38; N, 16.54. Found: C, 51.21; H, 2.26; N, 16.69.
4-(2,4-Difluorophenyl)-N-(4-(trifluoromethyl)phenyl)-5-(1H-1,2,4-triazol-
1-yl)thiazol-2-amine (5l). White solid; yield: 42.7%; mp 234–235 ꢀC. 1H NMR
(DMSO-d6=TMS): d 10.98 (s, 1H, NH), 8.71 (s, 1H, TrH), 8.21 (s, 1H, TrH), 7.85
(d, J ¼ 8.7 Hz, 2H, PhH), 7.70 (d, J ¼ 8.7 Hz, 2H, PhH), 7.61–7.66 (m, 1H, PhH),
7.16–7.31 (m, 2H, PhH). Anal. calcd. for C18H10BrF5N5S: C, 51.07; H, 2.38; N,
16.54. Found: C, 49.89; H, 2.11; N, 16.40.
4-(2,4-Difluorophenyl)-N-(2-chloro-4-methylphenyl)-5-(1H-1,2,4-triazol-1-
yl)thiazol-2-amine (5m). White solid; yield: 29.6%; mp 262–264 ꢀC. 1H NMR
(DMSO-d6=TMS): d 10.68 (s, 1H, NH), 8.70 (s, 1H, TrH), 8.21 (s, 1H, TrH), 7.85
(d, J ¼ 1.8 Hz, 1H, PhH), 7.58 (d, d, J ¼ 8.7 Hz, 1H, PhH), 7.40–7.44 (m, 1H,
PhH), 7.33 (s, 1H, PhH), 7.17–7.30 (m, 1H, PhH), 2.28 (s, 1H, CH3). Anal. calcd.
for C18H12ClF2N5S: C, 53.53; H, 3.00; N, 17.34. Found: C, 53.79; H, 2.75; N 17.49.
4-(2,4-Difluorophenyl)-N-(2,4-dichlorophenyl)-5-(1H-1,2,4-triazol-1-yl)
thiazol-2-amine (5n). White solid; yield: 37.1%; mp 176–178 ꢀC. 1H NMR
(DMSO-d6=TMS): d 8.68 (s, 1H, TrH), 8.35 (d, J ¼ 9 Hz, 1H, PhH), 8.19 (s, 1H,
TrH), 7.65 (d, J ¼ 2.4 Hz, 1H, PhH), 7.59 (d, d, J ¼ 8.7 Hz, 1H, PhH), 7.41 (d, d,
J ¼ 2.4 Hz, 1H, PhH), 7.13–7.29 (m, 2H, PhH). Anal. calcd. for C17H9Cl2F2N5S:
C, 48.13; H, 2.14; N, 16.51; Found: C, 47.99; H, 2.03; N, 16.79.
4-(2,4-Difluorophenyl)-N-(2, 4-dichlorophenyl)-5-(1H-1,2,4-triazol-1-yl)
thiazol-2-amine (5o). White solid; yield: 35.6%; mp 224–228 ꢀC. 1H NMR
(DMSO-d6=TMS): d 10.26 (s, 1H, NH), 8.71 (s, 1H, TrH), 8.57 (s, 1H, TrH), 8.21
(s, 1H, PhH), 7.53 (d, J ¼ 6.3 Hz, 2H, PhH), 7.12–7.31 (m, 3H, PhH). Anal. calcd.
for C17H9Cl2F2N5S: C, 48.13; H, 2.14; N, 16.51. Found: C, 48.29; H, 2.22; N, 16.63.
General Procedure for the Preparation of Title Compounds 5a–5d
Intermediate (3-2) (1.9 g, 0.005 mol), 0.06 mol of compound 4, and 20 mL of
ethanol were added into a 100-mL, four-necked, round-bottomed flask. The
mixtures were refluxed for 5–8 h (monitored by TLC). After the solution was cooled
to room temperature, it was poured into a beaker containing 50 mL water at
50–60 ꢀC. The solution was filtered, and the solid was recrystallized from ethanol
to give white solids 5a–5d in various yields.

3204
J.-B. LIU, H. DAI, AND X.-J. FANG
Selected Data
4-(2,4-Difluorophenyl)-N-phenyl-5-(1H-1,2,4-triazol-1-yl)thiazol-2-amine
(5a). White solid; yield: 30.6%; mp 218–220 ꢀC. 1H NMR (DMSO-d6=TMS): d 10.58
(s, 1H, NH), 8.69 (s, 1H, TrH), 8.20 (s, 1H, TrH), 8.21 (s, 1H, PhH), 7.59–7.66 (m,
3H, PhH), 7.15–7.38 (m, 4H, PhH), 7.00–7.05 (m, 1H, PhH). Anal. calcd. for
C17H11F2N5S: C, 57.46; H, 3.12; N, 19.71. Found: C, 57.21; H, 3.01; N 19.98.
4-(2,4-Difluorophenyl)-N-o-tolyl-5-(1H-1,2,4-triazol-1-yl)thiazol-2-amine
(5b). White solid; yield: 25.5%; mp 170–171 ꢀC. 1H NMR (DMSO-d6=TMS): d 9.78
(s, 1H, NH), 8.66 (s, 1H, TrH), 8.17 (s, 1H, TrH), 7.83 (d, J ¼ 7.5 Hz, 1H, PhH), 7.57
(d, d, J ¼ 8.7 Hz, 1H, PhH), 7.05–7.28 (m, 5H, PhH), 2.21 (s, 1H, CH3). Anal. calcd.
for C18H13F2N5S: C, 58.53; H, 3.55; N, 18.96. Found: C, 58.67; H, 3.41; N 19.21.
4-(2,4-Difluorophenyl)-N-m-tolyl-5-(1H-1,2,4-triazol-1-yl)thiazol-2-amine
(5c). White solid; yield: 27.4%; mp 203–205 ꢀC. 1H NMR (DMSO-d6=TMS): d 10.80
(s, 1H, NH), 8.94 (s, 1H, TrH), 8.20 (s, 1H, TrH), 7.91–8.01 (m, 1H, PhH), 7.58 (d,
J ¼ 9 Hz, 1H, PhH), 7.45 (s, 1H, PhH), 7.26–7.36 (m, 2H, PhH), 6.88 (d, J ¼ 7.5 Hz,
2H, PhH), 2.34 (s, 1H, CH3). Anal. calcd. for C18H13F2N5S: C, 58.53; H, 3.55; N,
18.96. Found: C, 58.29; H, 3.69; N, 19.22.
4-(2,4-Difluorophenyl)-N-m-tolyl-5-(1H-1,2,4-triazol-1-yl)thiazol-2-amine
(5d). White solid; yield: 27.4%; mp 203–205 ꢀC. 1H NMR (DMSO-d6=TMS): d
10.45 (s, 1H, NH), 8.68 (s, 1H, TrH), 8.19 (s, 1H, TrH), 7.62 (d, d, J ¼ 8.4 Hz,
1H, PhH), 7.52 (d, J ¼ 8.4 Hz, 2H, PhH), 7.21–7.30 (m, 2H, PhH), 7.16 (d,
J ¼ 8.1 Hz, 2H, PhH), 2.26 (s, 1H, CH3). Anal. calcd. for C18H13F2N5S: C, 58.53;
H, 3.55; N, 18.96. Found: C, 58.36; H, 3.62; N, 19.10.
Biological Activities
The title compounds 5 were screened for their biological activities in vitro against
the G. zeae, A. solani, P. asparagi, P. piricola, C. rachidicola, C. cucumerinum at the
concentration of 50 mg=L, and the relative inhibitory ratios (%) against these fungi
were listed in Table 1. The plant growth regulatory activities of the title compounds
were tested by wheat coleoptile and cucumber cotyledon test at the concentration of
10 mg=L. The biological activity of the title compounds were assayed at the Biological
Assay Centre, Nankai University according to procedures described previously.[28]
ACKNOWLEDGMENTS
We gratefully acknowledge the National Natural Science Foundation of China
(NNSFC) (Nos. 29872022 and 20172030) and the Research Fund for the Doctoral
Program of Higher Education (RFDP) (No. 9805520) for financial support.
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