Synthesis, structure, and biological activity of novel 1H-1,2,4-triazol-1- yl-thiazole derivatives

Article abstract of DOI:10.1080/00397910601031629

2-Amino-4-aryl-5-(1H-1,2,4-triazol-1-yl)thiazole derivatives were synthesized from the reaction of α-bromo substituted acetophenone and thiourea. The structures were confirmed by elemental analysis, 1H NMR and single crystal X-ray diffraction analysis. Biological evaluation showed that some of them possess antifungal and plant growth regulatory activities. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910601031629

This article was downloaded by: [University of Glasgow]
On: 21 May 2013, At: 10:43
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office:
Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International
Journal for Rapid Communication of
Synthetic Organic Chemistry
Publication details, including instructions for authors and subscription
information:
http://www.tandfonline.com/loi/lsyc20
Synthesis, Structure, and Biological Activity
of Novel 1H‐1,2,4‐Triazol‐1‐yl‐thiazole
Derivatives
Shao Ling a , Zhou Xin a , Zhang Qing a , Liu Jian‐Bing a , Jin Zhong a & Fang
Jian‐Xin a
a State Key Laboratory of Elemento‐organic Chemistry, Institute of
Elemento‐organic Chemistry, Nankai University, Tianjin, China
Published online: 25 Jul 2007.
To cite this article: Shao Ling , Zhou Xin , Zhang Qing , Liu Jian‐Bing , Jin Zhong & Fang Jian‐Xin (2007):
Synthesis, Structure, and Biological Activity of Novel 1H‐1,2,4‐Triazol‐1‐yl‐thiazole Derivatives, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 37:2,
199-207
To link to this article: http://dx.doi.org/10.1080/00397910601031629
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any substantial
or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or
distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation that the
contents will be complete or accurate or up to date. The accuracy of any instructions, formulae,
and drug doses should be independently verified with primary sources. The publisher shall not
be liable for any loss, actions, claims, proceedings, demand, or costs or damages whatsoever or
howsoever caused arising directly or indirectly in connection with or arising out of the use of this
material.

Synthetic Communicationsw, 37: 199–207, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910601031629
Synthesis, Structure, and Biological Activity
of Novel 1H-1,2,4-Triazol-1-yl-thiazole
Derivatives
Shao Ling, Zhou Xin, Zhang Qing, Liu Jian-Bing, Jin Zhong,
and Fang Jian-Xin
State Key Laboratory of Elemento-organic Chemistry, Institute of
Elemento-organic Chemistry, Nankai University, Tianjin, China
Abstract: 2-Amino-4-aryl-5-(1H-1,2,4-triazol-1-yl)thiazole
derivatives
were
synthesized from the reaction of a-bromo substituted acetophenone and thiourea.
The structures were confirmed by elemental analysis, 1H NMR and single crystal
X-ray diffraction analysis. Biological evaluation showed that some of them possess
antifungal and plant growth regulatory activities.
Keywords: biological activity, structure, synthesis, thiazole, triazole
INTRODUCTION
Thiazole derivatives are reported to exhibit diverse biological activities,[1]
such as antituberculous activities, bacteriostatic activities, and fungistaic
activities. Furthermore, triazole antifungals are known as potent inhibitors
of the cytochrome P450 monooxygensae in the process of fungal biosynthesis
of ergosterol, which is an important constitution of fungal cell membrane.[2]
These triazole antifungals, such as Sumiseven(S-3307D), propiconazole,
and imibenconazole, are applied widely to plant protection.
As a continuation of our studies on triazole derivatives,[3] and in search of
novel lead compounds with potential antifungicidal activities; we have sought
Received May 25, 2006
Address correspondence to Fang Jian-Xin, State Key Laboratory of Elemento-
organic Chemistry, Institute of Elemento-organic Chemistry, Nankai University,
Tianjin 300071, China. E-mail: fjx@nankai.edu.cn
199

200
S. Ling et al.
to synthesize such 2-aminothiazole compounds incorporating 1H-1,2,4-
triazole units. We herein report the synthesis and structure of a series of
novel 2-amino-4-aryl-5-(1H-1,2,4-triazol-1-yl)-1,3-thiazoles, which have
been characterized by spectra data and crystal X-ray diffraction analysis.
These compounds were also evaluated for their biological activities
including in vitro fungicidal and plant-growth regulatory activities.
RESULTS AND DISCUSSION
Synthesis
Brominating of substituted acetophenone 1a–1p in a conventional manner
(bromine/acetic acid) gave a-bromo-substituted acetophenone 2a–2p.
Compound 3a was synthesized by dropping a solution of 2a in acetone into
a mixture of 1H-1,2,4-triazole and triethylamine in acetone at 08C.
Compared with 3a, 3b–3p were obtained in low yield under the same con-
ditions. They were achieved in good yield by using anhydrous potassium
carbonate as a base and refluxing in chloroform. Because bromoacetyl-substi-
tuted benzene and dibromoacetyl-substituted benzene react with thiourea, they
could afford the same compound,[4] Treatment of 3 with light excessive
bromine in the presence of sodium acetate in acetic acid below 508C,
followed by heating with thiourea in ethanol, and alkalification with
ammonia solution (5%) via a Hantzsh reaction, afforded compounds 4a–4p
(Scheme 1).
Scheme 1. Synthetic routes of compounds 4a–4q: R ¼ H (a), p-F (b), p-Cl (c), o-Cl
(d), m-Cl (e), p-Br (f), o-Br (g), m-Br (h), p-OCH3 (i), p-Ph (j), 2,4-Cl (k), 3,4-Cl (l),
2,5-Cl (m), 2,3,4-Cl (n), 2,5-OCH3 (o), benzo[2,3-b](p) 2,4-F (q).

1H-1,2,4-Triazol-1-yl-thiazole Derivatives
201
The reaction was investigated under various conditions, including
solution (methanol, ethanol, water, and acetone), temperature, and ratio of
reagents (Table 1). The best yield was attained when compound 3 and
thiourea (1:2 molar ratios) were reacted in ethanol at reflux. In addition, we
cannot get the target production 4a if compound 3a, without being
bromated, directly reacted with thiourea under the effect of iodine.
Additionally, compound 4q was prepared in four steps starting from 2,
4-difurobenzene, and a-chloroacetyl chloride by the Friedel–Crafts
acylation reaction, and subsequent steps use the same method as that of
4b–4p (Scheme 1).
Structure
Figure 1 shows the molecular structure of 4c, which contains the following
three-plane subunit: the substituted phenyl ring C6-C11 (p1), the thiazole
ring (p2), and the triazole ring (p3). The dihedral angles between p1 and p2
and between p2 and p3 are 34.9 and 49.98, respectively. In the crystal
structure, weak intermolecular N-H. . .N interaction are found [N (5)-H
˚
˚
˚
(5B). . .N3: N-H ¼ 0.851A, H. . .N ¼ 2.311 A, N. . .N ¼ 3.005 A, and N (5)-
H (5B). . .N3 ¼ 109.38; symmetry code: (i) 3/2 2 x, 2 2 y, 1/2 þ z].
Biological Activities
Antifungal Activity
The assessments of in vitro fungicidal activity for some 2-aminothiazole con-
taining 1H-1,2,4-triazole compounds (4) were proceeding against five selected
fungi including P. zeae, A. solani, C. fulvum, P. piricola, and C. ara. Their
relative inhibitory ratios (%) against these fungi were determined, and the
results are reported in Table 2. The screening data revealed that the inhibitory
Table 1. Reaction conditions
Ratio of reagents
(mol) 3a:thiourea
Yield of 4a
(%)
Solution and condition
Acetone/reflux
1:1
1:1
1:1
1:1
1:1
1:1.5
1:2
0
Water/room temperature
Ethanol/room temperature
Methanol/reflux
Ethanol/reflux
Ethanol/reflux
0
0
21.6
34.0
50.4
60.1
Ethanol/reflux

202
S. Ling et al.
Figure 1. Molecular structure and crystallographic numbering scheme for compound
˚
4c. Selected bond lengths (A): S(1)–C(1) 1.758(4); S(1)–C(3) 1.764(4); Cl(1)–C(9)
1.758(4); N(1)–C(4) 1.356(4); N(1)–N(2) 1.370(4); N(1)–C(1) 1.414(4); N(2)–C(5)
1.314(4); N(3)–C(4) 1.318(4); N(3)–C(5) 1.363(4); N(4)–C(3) 1.311(4); N(4)–C(2)
1.405(4); N(5)–C(3) 1.359(4); C(1)–C(2) 1.364(4); C(2)–C(6) 1.494(4). Selected
bond angles (8): C(1)–S(1)–C(3) 87.7(12); C(4)–N(1)-N(2) 109.7(2); N(2)–N(1)–
C(1) 119.2(2); C(4)–N(3)–C(5) 102.0(2); C(3)–N(4)–C(2) 111.2(3); C(2)–
C(1)–N(1) 129.7(2); C(2)–C(1)–S(1) 111.50(18); N(4)–C(2)–C(6) 117.4(2);
N(4)–C(3)–S(1) 115.3(2); N(3)–C(4)–N(1) 110.4(2); C(11)–C(6)–C(2) 122.4(3);
C(7)–C(6)–C(2) 118.8(2).
ratios against A. solani and P. piricola of these compounds were slightly
higher than that of the other three.
The screening data indicated that compounds 4 showed a slight degree of
antifungal activity. Compared with known commercial agents, the antifungals
of this type of compounds were not encouraged (Table 2).
Plant-Growth Regulatory Activity
The plant-growth regulatory activity test adopted the wheat coleoptil segment
elongation and excised cucumber cotyledon root approaches. The results
showed that compounds 4k, 4l, and 4m could restrain the growth of wheat
coleoptile to a certain degree, and compound 4o has the activity to
accelerate the rootage of cucumber cotyledon when concentration was
1025 mg/mL (Table 3).

1H-1,2,4-Triazol-1-yl-thiazole Derivatives
203
Table 2. Antifungal activity of selected compound 4 (relative inhibitory ratio %)
Comp. (c ¼ 5 ꢀ 1025
mg/mL)
P. zeae A. solzni
C. ara
P. piricola C. fulvum
4a
4b
4c
4f
0
26.0
26.0
30.0
30.0
16.0
30.0
26.0
26.0
14.0
14.0
0
0
18.4
18.4
32.7
32.7
20.4
36.7
32.7
28.6
32.7
22.5
20.0
18.4
0
0
20.0
0
0
15.8
0
0
4i
0
0
4j
0
17.4
0
20.0
0
4k
4l
15.8
27.1
15.8
0
0
0
4m
4p
0
0
0
0
SUMMARY
To summarize, we synthesized a series of 2-amino-1,3-thiazole containing
1H-1,2,4-triazole derivatives 4a–4q, and their structures were established
1
on the basis of H NMR spectral data and elemental analysis. Finally, the
structure of compound 4c was confirmed by X-ray crystallographic studies.
These novel 2-amino-1,3-thiazole derivatives were also screened for their fun-
gicidal activities on five selected fungi and for plant-growth regulatory activi-
ties. The structure of compound 4 waits for further modification, in
expectation of getting better activities.
EXPERIMENT
Melting points (8C) were determined with X-4 digital melting-point apparatus
and are uncorrected. The H NMR spectra were measured on a Brucker AC-
1
300 spectrometer in DMSO-d6 solution with TMS as internal standard.
Elemental analysis was determined on Yanaco CHN Corder elemental
analyzer. X-ray diffraction data were recorded at 293 K on a Bruker
Table 3. Plant-growth regulatory activity of selected compound 4
c ¼ 1025 mg/mL
4h
4k
4l
4m
4o
Wheat coleoptile
Cucumber cotyledon root
2
2
þ
þ
þ
2
þ
2
2
2
Note. Wheat coleoptile: þ ꢁ10% ,25%; cucumber cotyledon
root: þ ꢁ50% ,100%.

204
S. Ling et al.
Smart1000 diffractometer (graphite-monochromatized Mo Ka radiation,
˚
l ¼ 0.71073 A). The substituted phenacyl bromide 2 was prepared by the lit-
erature method.[5]
Synthesis of a-(1H-1,2,4-Triazol-1-yl)-substituted acetophenone
(3a–3q)
Compound 3a was prepared by the literature method,[6] and compounds
3b–3q were synthesized as follows.
Anhydrous potassium carbonate (0.04 mol) and 1H-1,2,4-triazole
(0.04 mol) were added to a solution of compounds 2 (0.02 mol) in 250 ml
of chloroform. The reaction mixture was stirred and refluxed for 5–10 h
(tracked with thin-layer chromatography, TLC). Then the mixture was
cooled and filtered. The filtration was washed with water, dried, and evapo-
rated in vacuum to afford 3. They were purified by chromatography on silica
gel with the solvent system of ethyl acetate/petroleum ether (v/v ¼ 1:1).
Synthesis of 2-Amino-4-aryl-5-(1H-1,2,4-triazol-1-yl)-1,3-thiazole
(4a–4q)
Sodium acetate (4 mmol) was added to a solution of compound 3 (3 mmol) in
acetic acid (40 ml), then a solution of bromine (4 mmol) in acetic acid (10 ml)
was added dropwise at temperatures below 508C with continuous stirring.
After complete addition, the reaction mixture was stirred for another 3 h.
Following that, some water (60 ml) was added, and the formed precipitate
dissolved. Then the mixture was extracted in chloroform (3 ꢀ 15 ml), and
the organic solution was washed with saturated sodium bicarbonate untill
no gas was emitted washed with water, dried over magnesium sulfate, and
freed from the solvent by evaporation in vacuum.
With that, the residue was heated with thiourea (6 mmol) in ethanol under
reflux for 8 h, and the mixture was alkalified by ammonia solution (5%) and
allowed to cool overnight. The precipitated product was collected by filtration,
washed with water, and dried. Recrystallization from methanol or ethanol
afforded the desired 2-amino-4-aryl-5-(1H-1,2,4-triazol-1-yl)-1,3-thiazole
1
4 in various yields. The physical properties, elemental analysis data, and H
NMR spectra data of compounds 4 thus synthesized are reported in Tables
4 and 5, respectively.
Crystallographic Measurement
The colorless crystals with dimensions 0.22 mm ꢀ 0.16 mm ꢀ 0.14 mm
were mounted in a fiber. The structure was solved by direct methods and

Table 4. Physical data and elemental analysis of compounds 4a–4q
Elemental analysis (%) found (calcd).
Compound
R
Yield (%)
Mp (8C)
Formula (g/mol)
C
H
N
4a
4b
4c
4d
4e
4f
H
p-F
60.1
49.8
54.8
47.48
46.72
54.2
69.81
82.01
60.5
67.5
56.6
50.1
48.3
32.5
30.2
63.5
33.2
223–224
228–229
247–248
239–240
223–225
239–241
218–220
226–228
242–244
187–189
241–243
259–261
197–199
255–256
167–169
215–217
224–226
C11H9N5S (243.29)
54.31 (54.34)
50.51 (50.57)
47.56 (47.57)
47.30 (47.57)
47.64 (47.57)
41.05 (41.01)
21.65 (41.01)
41.03 (41.01)
52.67 (52.73)
63.85 (63.93)
42.22 (42.32)
42.22 (42.32)
42.42 (42.32)
37.91 (38.12)
51.51 (51.47)
61.32 (61.42)
47.36 (47.31)
3.73 (3.87)
3.15 (3.09)
3.02 (2.90)
3.11 (2.90)
3.03 (2.90)
2.54 (2.50)
2.48 (2.50)
2.70 (2.50)
4.11 (4.06)
4.01 (4.10)
2.30 (2.26)
2.30 (2.26)
2.26 (2.26)
2.00 (1.74)
4.20 (4.32)
3.98 (3.78)
2.51 (2.53)
28.79 (28.79)
26.58 (26.80)
25.25 (25.22)
24.98 (25.22)
25.32 (25.22)
21.60 (21.74)
21.65 (21.74)
21.70 (21.74)
25.78 (25.62)
21.78 (21.93)
22.41 (22.43)
22.41 (22.43)
22.20 (22.43)
19.99 (20.20)
22.95 (23.09)
23.77 (23.87)
25.16 (25.08)
C11H8FN5S (261.05)
C11H8ClN5S (277.73)
C11H8ClN5S (277.73)
C11H8ClN5S (277.73)
C11H8BrN5S (322.18)
C11H8BrN5S (322.18)
C11H8BrN5S (322.18)
C12H11N5OS (273.31)
C17H13N5S (319.38)
C11H7Cl2N5S (312.18)
C11H7Cl2N5S (312.18)
C11H7Cl2N5S (312.18)
C11H6Cl3N5S (346.62)
C13H13N5O2S (303.34)
C15H11N5S (293.35)
C11H7F2N5S (279.27)
p-Cl
o-Cl
m-Cl
p-Br
o-Br
m-Br
4g
4h
4i
p-CH3O
p-Ph
2,4-Cl
4j
4k
4l
3,4-Cl
2,5-Cl
4m
4n
4o
4p
4q
2,3,4-Cl
2,5-CH3O
Benzo[2,3-b]
2,4-F

206
S. Ling et al.
Table 5. 1H NMR spectral data of compounds 4a–4q
Compound
1H NMR (DMSO/TMS, d)
4a
8.73 (s, 1H, Tr-H), 8.30 (s, 1H, Tr-H), 7.54 (s, 2H, NH2), 7.30–7.14
(m, 5H, Ar-H)
4b
4c
4d
4e
4f
8.76 (s, 1H, Tr-H), 8.30 (s, 1H, Tr-H), 7.56 (s, 2H, NH2), 7.22–7.11
(m, 4H, Ar-H)
8.76 (s, 1H, Tr-H), 8.30 (s, 1H, Tr-H), 7.58 (s, 2H, NH2), 7.39–7.36
(q, 2H, Ar-H), 7.16–7.13 (q, 2H, Ar-H)
8.40 (d, 1H, Tr-H, J ¼ 1.2 Hz), 8.09 (d, 1H, J ¼ 1.2 Hz), 7.50 (s, 2H,
NH2), 7.45–7.33 (m, 4H, Ar-H)
8.80 (s, 1H, Tr-H), 8.34 (s, 1H, Tr-H), 7.62 (s, 2H, NH2), 7.40–7.00
(m, 4H, Ar-H)
8.76 (s, 1H, Tr-H), 8.30 (s, 1H, Tr-H), 7.60 (s, 2H, NH2), 7.53–7.49
(q, 2H, Ar-H), 7.10–7.07 (q, 2H, Ar-H)
4g
4h
4i
8.36 (s, 1H, Tr-H), 8.09 (s, 1H, Tr-H), 7.50 (s, 2H, NH2), 7.42–7.29
(m, 4H, Ar-H)
8.80 (s, 1H, Tr-H), 8.34 (s, 1H, Tr-H), 7.62 (s, 2H, NH2), 7.51–7.02
(m, 4H, Ar-H)
8.73 (s, 1H, Tr-H), 8.29 (s, 1H, Tr-H), 7.49 (s, 2H, NH2), 7.10–7.07
(q, 2H, Ar-H), 6.86–6.83 (q, 2H, Ar-H), 3.820 (s, 3H, OCH3)
8.79 (s, 1H, Tr-H), 8.33 (s, 1H, Tr-H), 7.56 (s, 2H, NH2), 7.67–7.23
(m, 9H, Ar-H)
4j
4k
4l
8.48 (s, 1H, Tr-H), 8.10 (s, 1H, Tr-H), 7.54 (s, 2H, NH2), 7.63–7.44
(t, 3H, Ar-H)
8.81 (s, 1H, Tr-H), 8.34 (s, 1H, Tr-H), 7.64 (s, 2H, NH2), 7.60–6.99
(m, 3H, Ar-H)
4m
4n
4o
4p
4q
8.52 (s, 1H, Tr-H), 8.11 (s, 1H, Tr-H), 7.55 (s, 2H, NH2), 7.51–7.45
(m, 3H, Ar-H)
8.55 (s, 1H, Tr-H), 8.12 (s, 1H, Tr-H), 7.58 (s, 2H, NH2), 7.68, 7.50
(d, 1H, Ar-H, J ¼ 8.4), 7.43, 7.41 (d, 1H, Ar-H, J ¼ 8.4)
8.34 (s, 1H, Tr-H), 8.08 (s, 1H, Tr-H), 7.40 (s, 2H, NH2), 6.97–6.82
(m, 3H, Ar-H), 3.40, 3.38 (d, 3H, 2-OCH3), 3.35 (s, 3H, 5-OCH3)
8.36 (s, 1H, Tr-H), 8.04 (s, 1H, Tr-H), 7.43 (s, 2H, NH2), 7.94–7.39
(m, 7H, Ar-H)
8.60 (s, 1H, Tr-H), 8.13 (s, 1H, Tr-H), 7.47 (s, 2H, NH2), 7.55–7.09
(m, 3H, Ar-H)
completed by difference Fourier map using the SHELXL-97 program
and refined by full-matrix least-squares on F2. The nonhydrogen atoms
were refined anisotropically and hydrogen atoms were added according to
theoretical models. Crystallographic data: orthorhombic, space group
P2(1)2(1)2(1) with cell dimensions of a ¼ 7.540(15) nm, b ¼ 11.27(2) nm,
c ¼ 14.65(3) nm, a ¼ 90.008, b ¼ 90.008, g ¼ 90.008, V ¼ 1.245(4) nm3,
Z ¼ 4, m ¼ 0.462 mm21
.

1H-1,2,4-Triazol-1-yl-thiazole Derivatives
207
SUPPLEMENTARY MATERIAL
Crystallographic data for the structure 4c has been deposited in the Cambridge
Crystallographic Data Center, CCDC No. 283871. Copies of this information
may be obtained free of charge from the director, CCDC, 12 Union Road,
Cambridge, CB2 1EZ, U.K. (fax: þ44-1223-336033, e-mail: deposit@ccdc.
cam.ac.uk, or http:// www.ccdc.cam.ac.uk).
ACKNOWLEDGMENTS
We gratefully acknowledge the National Natural Science Foundation of China
(NNSFC) (No. 20172030) and the Key Project of Chinese Ministry of
Education (No. 105046) for financial support.
REFERENCES
1. (a) Smia, M. S.; Maghray, A. S.; Mohamed, A. R.; Mohamed, A. K. Heteroatom
Chem. 2000, 11, 362–369; (b) Bilodeau, M. T.; Balitza, A. E.; Koester, T. J.;
Manley, P. J.; Rodman, L. D.; Buser-Doepner, C.; Coll, K. E.; Fernandes, C.;
Gibbs, J. B.; Heimbrook, D. C.; Huckle, W. R.; Kohl, N.; Lynch, J. J.; Mao, X.;
McFall, R. C.; McLoughlin, D.; Miller-Stein, C. M.; Rickert, K. W.; Sepp-
Lorenzino, L.; Shipman, J. M.; Subramanian, R.; Thomas, K. A.; Wong, B. K.;
Yu, S.; Hartman, G. D. Potent N-(1,3-thiazole-2-yl)pyridin-2-amine vascular endo-
thelial growth factor receptor tyrosine kinase inhibitors with excellent pharmacoki-
netics and low affinity for the hERG ion channel. J. Med. Chem. 2004, 47 (25),
6363–6372; (c) Wang, S.; Meads, C.; Wood, G.; Osnowski, A.; Anderson, S.;
Yuill, R.; Thomas, M.; Mwzna, M.; Jackson, W.; Midgley, C.; Griffiths, G.;
Fleming, I.; Green, S.; McNae, I.; Wu, S. Y.; Mclnness, C.; Zheleva, D.;
Walkinshaw, M. D.; Fischer, P. M. 2-Anilino-4-(thiazol-5-yl)pyrimidine CDK inhibi-
tors: Synthesis, SAR Analysis, X-ray crystallography, and biological activity. J. Med.
Chem. 2004, 47 (7), 1662–1675; (d) Dayan, F. E.; Vincent, A. C.; Romagni, J. G.;
Allen, S. N.; Duke, S. O.; Duke, M. V.; Bowling, J. J.; Zjawiony, J. K. Amino-
and urea-substituted thiazoles inhibit photosynthetic electron transfer. J. Agric.
Food Chem. 2004, 48 (8), 3689–3693.
2. Miyauchi, H.; Kozuki, K.; Tanio, T.; Ohashi, N. Bioorg. Med. Chem. Lett. 1995,
5 (14), 1479–1482.
3. (a) Jin, Z.; Huo, A. H.; Li, T.; Hu, Y.; Liu, J. B.; Fang, J. X. Synthesis, structures and
biological activity research of novel ferrocenyl-containing 1H-1,2,4-triazole
derivatives. J. Organomet. Chem. 2005, 690, 1226–1232; (b) Fang, J. X.; Jin, Z.;
Li, Z. M.; Liu, W. Preparation, characterization and biological activities of novel
ferrocenyl-substituted azaheterocycle compounds. Appl. Organomet. Chem. 2003, 17,
145–153; (c) Shao, L.; Hu, Y.; Tao, W. F.; Jin, Z.; Fang, J. X. [2-(4-Nitophenoxyl)-
2-(1H-1,2,4-triazol-1-yl) acetyl]ferrocene. Acta Cryst. E 2005, 61, m1837–m1839.
4. Sakata, M.; Shirakawa, Y.; Kamata, N.; Sakaguchi, Y.; Nishino, H.; Ouyang, J.;
Kurosawa, K. J. Heterocycl. Chem. 2000, 37, 269–274.
5. Joshi, K. C.; Pathak, V. N.; Sharma, S. Org. Prep. Proc. Int. 1985, 17, 146.
¨
¨
6. Timmler, H.; Kramer, W.; Buchel, K. H.; Kaspers, H.; Brandes, W. US Patent 4 776
877, 1988.