Synthesis and biological activity research of novel ferrocenyl-containing thiazole imine derivatives

Article abstract of DOI:10.1016/j.jorganchem.2006.10.059

A series of novel N-substituted benzylidene-4-ferrocenyl-5-(1H-1,2,4-triazol-1-yl)-1,3-thiazol-2-amine derivatives were synthesized by condensation of substituted-benzaldehydes with 2-amino-4-ferrocenyl-5-(1H-1,2,4-triazol-1-yl)-1,3-thiazole and characterized by ¹H NMR, X-ray diffraction and elemental analysis. The results of bioassay showed that some title compounds exhibited some degree of plant growth regulatory and antifungal activities.

Full text of DOI:10.1016/j.jorganchem.2006.10.059

Journal of Organometallic Chemistry 692 (2007) 991–996
www.elsevier.com/locate/jorganchem
Synthesis and biological activity research of novel
ferrocenyl-containing thiazole imine derivatives
*
Haibo Yu, Ling Shao, Jianxin Fang
Institute and State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Weijin Road 94, Tianjin 300071, PR China
Received 18 July 2006; received in revised form 22 September 2006; accepted 27 October 2006
Available online 7 November 2006
Abstract
A series of novel N-substituted benzylidene-4-ferrocenyl-5-(1H-1,2,4-triazol-1-yl)-1,3-thiazol-2-amine derivatives were synthesized by
condensation of substituted-benzaldehydes with 2-amino-4-ferrocenyl-5-(1H-1,2,4-triazol-1-yl)-1,3-thiazole and characterized by 1H
NMR, X-ray diffraction and elemental analysis. The results of bioassay showed that some title compounds exhibited some degree of
plant growth regulatory and antifungal activities.
ꢀ 2006 Elsevier B.V. All rights reserved.
Keywords: Ferrocene; Triazole; Thiazole; Biological activity; Synthesis
1. Introduction
cete and Ascomycete groups of fungi. These compounds
are known to inhibit the biosynthesis of ergosterol in fungi.
In addition to their fungicidal activity, they also possess a
very high level of plant growth regulatory activity on a
wide variety of crops [14]. Recently, we reported some
ferrocene-containing triazole compounds with biological
activities, such as ferrocene-triadimefon analogues [15];
1-ferrocenyl-3-aryl-2-(1H-1,2,4-triazol-1-yl)-prop-2-en-1-one
derivatives [16]; 1-phenyl-3-ferrocenyl-4-triazolyl-5-aryl-
dihydropyrazole [17]; 3-aryl-1-ferrocenylpropenone [18].
All the compounds show some degree of fungicidal activi-
ties and plant growth regulatory activities.
In order to search novel thiazole compounds with
potent biological activities, our research group has synthe-
sized some compounds which include aromatic group,
thiazole and triazole fragment and obtained some biologi-
cal compounds. For examples, N-(4-F-benzylidene)-4-phe-
nyl-5-(1H-1,2,4-triazol-1-yl)-1,3-thiazol-2-amine exhibits
18.9% inhibitory ratio against P. pircola, 20.0% against
A. solani, 22.2% against C. ara, 45.7 against P. pircola on
the antifungal activities, respectively. It also was assayed
for plant growth regulatory against Rape hypocotyls, the
inhibitory ratio is À1.8%. The substitution of a phenyl
group by a ferrocenyl group in a bioactive compound
The thiazole ring is very important in nature. For exam-
ple, it exists in thiamine, a coenzyme required for the
oxidative decarboxylation of a-keto acids. A tetrahydro-
thiazole also appears in the skeleton of penicillin which is
one of the first and still most important of the broad-
spectrum antibiotics. Thiazolamines are key intermediates
for synthesizing many pharmaceuticals [1]. Some thiazoli-
dones are valuable medicines [2,3]. It is obvious that com-
pounds with the thiazole ring have potential biological
activity. We also know that some Schiff bases are effective
antitumor and antibiotic drugs [4,5].
For many years, much interest has focused on ferrocenyl
derivatives for their bioactivity [6,7]. Incorporation of fer-
rocene fragment into the molecule of an organic compound
often leads to unexpected biological activity, which is due
to their different membrane permeation properties and
anomalous metabolism [8–12]. On the other hand, com-
pounds containing the 1H-1,2,4-triazole ring system are
highly active fungicides [13], especially on the Basidiomy-
*
Corresponding author. Tel.: +86 22 2350 5330.
E-mail address: fjx@nankai.edu.cn (J. Fang).
0022-328X/$ - see front matter ꢀ 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2006.10.059

992
H. Yu et al. / Journal of Organometallic Chemistry 692 (2007) 991–996
was expected to induce great changes in molecular proper-
ties, such as the solubility and hydrophobicity [19,20].
Following our interesting in synthesis of new thiazole and
triazole compounds with potent biological activities, we
engage in the incorporation of ferrocene fragment into
thiazole compound. In the present work, we describe the
synthesis, characterization and bioactivities of some
N-substituted benzylidene-4-ferrocenyl-5-(1H-1,2,4-triazol-
1-yl)-1,3-thiazol-2-amine derivatives.
gle peak between 8.90 and 9.60 ppm. The protons of the
triazole appear as two single peaks between 8.06 and
8.40 ppm.
All protons in the compounds have been identified and
the total number of protons calculated from the integration
curve tallies with what is expected from the molecular
formula.
2.3. Crystal structure
2. Results and discussion
An organe-plate crystal of compound 5a was recrystal-
lized from acetonitrile. Fig. 1 shows the molecular structure
of compound 5a and gives the atom numbering scheme.
The selected bond distances and angels of the compound
5a are listed in Table 1. Three planar rings in the com-
pound 5a are (i) the phenyl ring C17–C22; (ii) the thiazole
ring C11/C12/S1/C15/N4; (iii) the triazole ring N1/C13/
N3/N2/C14. The dihedral angles between planar i and ii
and between planar ii and iii are 42.19 (13) and 81.15
(12), respectively [28].
2.1. Preparation
´
The compound 1 was prepared as described by Tarraga
et al. [21]. Whereafter, metallation of acetylferrocene with
LDA at À78 ꢁC followed by sequential treatment with
trimethylchlorosilane and an excess of NBS provided the
a-bromoacetylferrocene (1) in 80% yield, along with small
amount of a,a-dibromoacetylferrocene. Conversion of
compound
1 into a-triazolylacetyl-ferrocene (2) was
achieved in perfect yield (95%) by using anhydrous potas-
sium carbonate as a base [17].
2.4. Biological activities
2-Bromo-2-(1H-1,2,4-triazol-1-yl)-acetylferrocene was
The assessment of fungicidal activities in vitro for these
2-thiazoleimine compounds 5a–q were examined against
four selected fungi including P. zeae, A. solani, P. pircola
and C. ara at the concentration of 50 mg/L. The screening
´
prepared by the same methods described by Tarraga and
co-workers [21], the yield of compound 3 is 83% and no
by-products were found. Several methods for synthesis of
2-thiazolamine have been reported [22–26]. We prepared
ferrocenyl-containing 2-thiazolamine with Hantzsch’s
method [27], the yield was 90%. When the amine condensed
with aromatic aldehydes, the target N-substituted benzyli-
dene-4-ferrocenyl-5-(1H-1,2,4-triazol-1-yl)-1,3-thiazol-2-
amine (5a–q) were readily obtained in good to excellent
yields (Scheme 1).
1
2.2. H NMR
All the compounds were completely characterized by 1H
1
NMR spectroscopy. The H NMR data of the title com-
pounds are listed in Table 4.
1
The H NMR chemical shifts of ferrocene are in char-
Fig. 1. The molecular structure of compound 5a.
acter. The chemical shifts of the unsubstituted cyclopent-
adiene ring appear between 4.12 and 4.25 ppm as a single
peak. The chemical shifts of the substituted cyclopentadi-
ene ring appear as two peaks between 4.25 and
4.29 ppm. The protons of the imine display an acute sin-
Table 1
Selected bond lengths and angels of compound 5a
˚
Bond lengths (A)
Bond angles (ꢁ)
S (1)–C (12)
S (1)–C (15)
N (1)–C (13)
N (1)–C (14)
N (2)–C (14)
N (2)–N (3)
N (3)–C (13)
N (4)–C (15)
N (4)–C (11)
N (5)–C (16)
N (5)–C (15)
1.729 (3)
1.743 (3)
1.310 (4)
1.343 (6)
1.317 (5)
1.368 (4)
1.337 (4)
1.299 (4)
1.379 (3)
1.249 (4)
1.386 (4)
C (13)–N (1)–C (14)
C (14)–N (2)–N (3)
C (13)–N (3)–N (2)
C (15)–N (4)–C (11)
C (16)–N (5)–C (15)
C (11)–C (12)–S (1)
N (3)–C (12)–S (1)
N (1)–C (13)–N (3)
N (2)–C (14)–N (1)
N (4)–C (15)–S (1)
N (5)–C (15)–S (1)
N (5)–C (16)–C (17)
102.3 (3)
100.1 (3)
110.4 (3)
111.3 (2)
121.4 (3)
111.8 (2)
121.2 (2)
110.2 (3)
116.9 (4)
115.4 (2)
123.2 (2)
122.5 (3)
Br
Br
N
N
N
N
N
N
K2CO3
LDA, ClSiMe3
NBS
Fe
O
Fe
O
Fe
O
1,2,4-triazole
3
2
1
Fe
Fe
N
N
X
benzene
ethanol
thiourea
N
N
5
CH
N
NH2
arylaldehyde
S
S
4
N
N
N
N
Scheme 1.

H. Yu et al. / Journal of Organometallic Chemistry 692 (2007) 991–996
993
Table 2
Biological activities of the title compound 5
Entry
X
Relative inhibitory ratio (%)
P. zeae
A. solani
P. pircola
C. ara
Plant growth
regulatory activity
5a
5b
5c
5d
5e
5f
H
4-F
3-F
2-Cl
2-F
4-Cl
2,4-Cl2
2,4-Me2
2-MeO
2,4-MeO2
4-Me
2-OH
2-NO2
3-OH
4-Br
22.6
19.4
19.4
19.4
25.8
43.4
18.9
9.7
0
45.9
55.4
50.0
47.3
58.1
50.0
36.8
47.3
44.6
52.7
58.1
56.8
62.2
45.9
45.9
56.8
54.1
10.0
10.0
5.0
10.0
15.0
23.5
11.8
0
59.3
61.4
54.4
52.3
60.7
49.0
51.6
50.9
56.5
55.1
46.7
55.8
40.3
50.9
53.7
41.7
58.6
16.7
16.7
16.7
16.7
22.4
20.0
8.3
0
8.3
12.5
0
29.2
12.5
8.3
8.3
0
5g
5h
5i
9.7
6.5
5.0
5j
10.0
10.0
15.0
35.0
10.0
0
5k
5l
19.4
29.0
45.2
22.6
9.7
5m
5n
5o
5p
5q
4-OH
4-MeO
0
9.7
10.0
10.0
data revealed that all the title compounds 5 showed some
antifungal activities, among which 5m showed 62.2% inhib-
itory ratio against P. pircola. The plant growth regulatory
activities of the title compounds were tested by Rape
hypocotyls test at the concentration of 10 mg/L. All the
compounds exhibited some inhibitory activities on the
growth of Rape hypocotyls, and the inhibitory ratio is
40.3–61.4%. The data of biological activities of the title
compounds 5 were outlined in Table 2.
3. Summary
A series of ferrocene-containing N-substituted benzyli-
dene-4-ferrocenyl-5-(1H-1,2,4-triazol-1-yl)-1,3-thiazol-2-
amine derivatives were synthesized and their structures
were verified by elemental analysis, 1H NMR and
X-ray diffraction analysis. These novel 2-thiazoleimine
derivatives were screened for their biological activities.
The screening data revealed that compounds 5 show
some antifungal activities and plant growth regulatory
activity. Further structure modification and optimization
of these ferrocene-containing thiazole derivatives are
necessary.
To our disappointment, the results of the screening of
antifungal and plant growth regulatory activities are not
exciting, but compared to the phenyl substituted thiazole
imine compound, the biological activities are increased. It
is interesting to note that the fungicidal activities in vitro
of the title compounds appeared to be weakly associated
with the substituent group on the benzene cycle. The fun-
gicidal activities of the derivatives with electron-withdraw-
ing groups on phenyl fragments are superior to those with
electron-donating groups, but the effect is not obviously.
The X-ray structure of 5a shows that, because of the
bulkiness of ferrocene, the ferrocene group was spatially
repulsed and swerved to nearby triazole group (Fig. 1),
and most of this series of compounds display low fungi-
cidal activity. This may imply that a bulky group close
to the triazole cycle is not a wise choice for the generation
of compounds with fungicidal activities. In addition, it is
well known that the antifungal activities of the triazole
derivatives are related to their interference with steroid
biosynthesis and fungal cell-wall formation mediated by
ferrous cytochrome-P450 enzymes [29]. It was also
hypothesized that binding of the triazole to ferrous atom
of cytochrome-P450 enzymes was replaced with binding
of the triazole to ferrous atom of ferrocene group by
intramolecular or intermolecular interaction, as a result,
the antifungal activities of title compounds 5a–q was
depressed.
4. Experimental
All reactions were carried out under nitrogen atmo-
sphere and monitored by TLC. All solvents were pre-dried
and distilled prior to use. All melting points were deter-
mined on a Yanaco-241 apparatus and thermometer was
1
uncorrected. The H NMR spectra were measured on a
Brucker AC-300 spectrometer in CDCl3 or d6-DMSO solu-
tion with TMS as internal standard. Elemental analyses
were determined on a Yanaco CHN Corder elemental
analyzer.
4.1. Synthesis of 2-bromo-2-(1H-1,2,4-triazol-1-yl)-
acetylferrocene (3)
n-Butyllithium 1.6 M in hexane (45.2 mL, 72.3 mmol)
was dropped to a solution of diisopropylamine (7.32 g,
72.3 mmol) in dry THF (20 mL), at À78 ꢁC under nitrogen
atmosphere. The mixture was stirred at À78 ꢁC for 1 h.
Then, a solution of a-(1H-1,2,4-triazol-1-yl)-acetyl-ferro-
cene (12.93 g, 43.8 mmol) in 100 mL dry THF was dropped.
The mixture was stirred for 2 h, and chlorotrimethylsilane

994
H. Yu et al. / Journal of Organometallic Chemistry 692 (2007) 991–996
(6.30 g, 57 mmol) was added in dropwise. After 4 h under
these reaction conditions, NBS (10.14 g, 57 mmol) was
added in a single addition, and the mixture was stirred until
the reaction reached room temperature (6–8 h). The reac-
tion mixture was filtered through a silica gel layer, the
resulting solution was evaporated to dryness and chromato-
Table 3
Physical properties and elemental analysis data for compound 5
Entry
X
Yield (%)
M.p. (ꢁC)
Elemental analysis data (Calc. %)
C
H
N
5a
5b
5c
5d
5e
5f
H
4-F
3-F
2-Cl
2-F
4-Cl
2,4-Cl2
2,4-Me2
2-MeO
2,4-MeO2
4-Me
2-OH
2-NO2
3-OH
4-Br
88
85
64
84
80
62
80
82
79
82
82
69
70
68
91
65
89
165–166
171–172
152–153
157–158
152–153
199–200
169–170
151–152
160–161
156–157
161–162
167–168
69–70
60.27 (60.15)
57.75 (57.78)
57.83 (57.78)
55.79 (55.77)
58.01 (57.78)
55.71 (55.77)
51.89 (51.99)
61.64 (61.68)
58.76 (58.86)
58.01 (57.72)
61.20 (60.94)
58.08 (58.03)
54.31 (54.56)
57.92 (58.03)
50.95 (50.99)
58.34 (58.03)
58.73 (58.86)
4.04 (3.90)
3.57 (3.53)
3.65 (3.53)
3.47 (3.40)
3.75 (3.53)
3.45 (3.40)
3.08 (2.98)
4.75 (4.53)
4.08 (4.29)
4.12 (4.24)
4.12 (4.22)
3.87 (3.76)
3.52 (3.33)
3.96 (3.76)
3.17 (3.11)
4.01 (3.76)
3.95 (4.08)
16.03 (15.94)
15.12 (15.31)
15.31 (15.31)
14.55 (14.78)
15.25 (15.31)
14.66 (14.78)
13.85 (13.78)
14.95 (14.98)
14.83 (14.92)
13.92 (14.02)
15.40 (15.45)
15.36 (15.38)
17.30 (17.35)
15.22 (15.38)
13.57 (13.51)
15.36 (15.38)
14.70 (14.92)
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
5q
159–160
198–199
156–157
159–160
4-OH
4-MeO
Table 4
1H NMR date for compound 5
Entry
X
H
1H NMR spectra data (d, CDCl3)
5a
9.02 (s, 1H, N@CH), 8.31 (s, 1H, TrH), 8.25 (s, 1H, TrH), 7.63–7.51 (m, 5H, ArH), 4.27 (s, 2H, C5H4), 4.26 (s, 2H, C5H4), 4.13 (s,
5H, C5H5)
5b
5c
4-F
3-F
8.98 (s, 1H, N@CH), 8.08 (s, 1H, TrH), 8.06 (s, 1H, TrH), 8.06–7.20 (m, 4H, ArH), 4.28 (s, 2H, C5H4), 4.25 (s, 2H, C5H4), 4.13 (s,
5H, C5H5)
9.03 (s, 1H, N@CH), 8.31 (s, 1H, TrH), 8.25 (s, 1H, TrH), 7.81–7.29 (m, 4H, ArH), 4.28 (s, 2H, C5H4), 4.25 (s, 2H, C5H4), 4.13 (s,
5H, C5H5)
5d
5e
2-Cl
2-F
9.50 (s, 1H, N@CH), 8.40 (s, 1H, TrH), 8.27 (s, 1H, TrH), 8.31–7.42 (m, 4H, ArH), 4.28 (s, 4H, C5H4), 4.14 (s, 5H, C5H5)
9.35 (s, 1H, N@CH), 8.31 (s, 1H, TrH), 8.25 (s, 1H, TrH), 7.62–7.17 (m, 4H, ArH), 4.28 (s, 2H, C5H4), 4.26 (s, 2H, C5H4), 4.13 (s,
5H, C5H5)
5f
4-Cl
9.01 (s, 1H, N@CH), 8.31 (s, 1H, TrH), 8.25 (s, 1H, TrH), 8.01–7.50 (m, 4H, ArH), 4.28 (s, 2H, C5H4), 4.25 (s, 2H, C5H4), 4.13 (s,
5H, C5H5)
5g
5h
5i
2,4-Cl2
2,4-Me2
2-MeO
2,4-MeO2
4-Me
9.45 (s, 1H, N@CH), 8.35 (s, 1H, TrH), 8.31 (s, 1H, TrH), 8.25–7.39 (m, 3H, ArH), 4.28 (s, 2H, C5H4), 4.27 (s, 2H, C5H4), 4.13 (s,
5H, C5H5)
9.27 (s, 1H, N@CH), 8.30 (s, 1H, TrH), 8.24 (s, 1H, TrH), 8.16–7.11 (m, 3H, ArH), 4.27 (s, 2H, C5H4), 4.26 (s, 2H, C5H4), 4.13 (s,
5H, C5H5), 2.64 (s, 3H, CH3), 2.40 (s, 3H, CH3)
9.40 (s, 1H, N@CH), 8.31 (s, 1H, TrH), 8.25 (s, 1H, TrH), 7.58–6.98 (m, 4H, ArH), 4.27 (s, 2H, C5H4), 4.27 (s, 2H, C5H4), 4.13 (s,
5H, C5H5), 3.96 (s, 3H, OCH3)
9.24 (s, 1H, N@CH), 8.30 (s, 1H, TrH), 8.24 (s, 1H, TrH), 8.26–6.41 (m, 3H, ArH), 4.27 (s, 2H, C5H4), 4.26 (s, 2H, C5H4), 4.13 (s,
5H, C5H5), 3.93 (s, 3H, OCH3), 3.91 (s, 3H, OCH3)
8.96 (s, 1H, N@CH), 8.31 (s, 1H, TrH), 8.25 (s, 1H, TrH), 7.96–7.23 (m, 4H, ArH), 4.27 (s, 2H, C5H4), 4.26 (s, 2H, C5H4), 4.13 (s,
5H, C5H5), 2.47 (s, 3H, CH3)
12.11 (s, 1H, OH), 9.27 (s, 1H, N@CH), 8.31 (s, 1H, TrH), 8.25 (s, 1H, TrH), 7.58–7.01 (m, 4H, ArH), 4.29 (s, 2H, C5H4), 4.25 (s,
2H, C5H4), 4.13 (s, 5H, C5H5)
5j
5k
5l
2-OH
5m
5n
5o
5p
5q
2-NO2
3-OH
9.60 (s, 1H, N@CH), 8.31 (s, 1H, TrH), 8.24 (s, 1H, TrH), 8.46–7.73 (m, 4H, ArH), 4.28 (s, 2H, C5H4), 4.26 (s, 2H, C5H4), 4.13 (s,
5H, C5H5)
11.99 (s, 1H, OH), 8.95 (s, 1H, N@CH), 8.31 (s, 1H, TrH), 8.25 (s, 1H, TrH), 7.57–7.10 (m, 4H, ArH), 4.27 (s, 2H, C5H4), 4.25 (s,
2H, C5H4), 4.12 (s, 5H, C5H5)
8.99 (s, 1H, N@CH), 8.30 (s, 1H, TrH), 8.25 (s, 1H, TrH),7.92–7.66 (m, 4H, ArH), 4.28 (s, 2H, C5H4), 4.24 (s, 2H, C5H4), 4.12 (s,
5H, C5H5)
9.88 (s, 1H, OH), 8.87 (s, 1H, N@CH), 8.31 (s, 1H, TrH), 8.30 (s, 1H, TrH), 7.96–6.97 (m, 4H, ArH), 4.28 (s, 2H, C5H4), 4.25 (s,
2H, C5H4), 4.13 (s, 5H, C5H5)
4-Br
4-OH
4-MeO
8.90 (s, 1H, N@CH), 8.30 (s, 1H, TrH), 8.25 (s, 1H, TrH), 8.02–7.02 (m, 4H, ArH), 4.26 (s, 2H, C5H4), 4.26 (s, 2H, C5H4), 4.13 (s,
5H, C5H5), 3.92 (s, 3H, OCH3)

H. Yu et al. / Journal of Organometallic Chemistry 692 (2007) 991–996
995
graph on a silica gel column using ethyl acetate/petroleum
ether (1:3) as eluent, 2-bromo-2-(1H-1,2,4-triazol-1-yl)-
acetylferrocene (3) was obtained as an organic crystal in
83% yield; m.p. 114–116 ꢁC; 1H NMR (d6-DMSO, d
ppm): 9.08 (s, 1H, TrH), 8.23 (s, 1H, TrH), 5.08 (s, 1H,
CHBr), 4.80 (s, 2H, C5H4), 4.30 (s, 5H, C5H5), 3.41 (s,
2H, C5H4).
of piperidine was added to the mixture solution. The
solution was heated and refluxed in a 50 mL flask
equipped with a Dean-Stark trap condenser until no
water appeared (ca. 2 h). After the reaction solution
was concentrated and purified by silica column chroma-
tography using ethyl acetate/petroleum ether (1:3) as elu-
ent, an organic crystal was obtained. The physical
1
properties, elemental analysis data and H NMR spectra
4.2. Synthesis of 2-amino-4-ferrocenyl-5-(1H-1,2,4-triazol-
1-yl)-1,3-thiazole (4)
of compounds 5a–q are given in Tables 3 and 4,
respectively.
2-Bromo-2-(1H-1,2,4-triazol-1-yl)-acetylferrocene
(3)
4.4. X-ray crystallography
1.39 g (3.7 mmol) and thiourea 0.40 g (5.3 mmol) were dis-
solved in 10 mL of warm ethanol. The mixture was refluxed
for 3 h and then poured into 80 mL of ammonia spirit. The
yellow solids that formed were filtered and dried. After
recrystallization from the solvent of methanol, 1.30 g of
amine 4 was obtained. 1H NMR (d6-DMSO, d ppm):
8.82 (s, 1H, TrH), 8.27 (s, 1H, TrH), 7.44 (s, 2H, NH2),
4.42 (s, 2H, C5H4), 4.00 (s, 5H, C5H5), 3.84 (s, 2H,
C5H4). Yield 90%; m.p. 248–250 ꢁC.
A crystal of compound 5a was obtained from acetoni-
trile. Diffraction measurements of compound 5a was car-
ried out on a Bruker SMART 1000CCD diffractometer
operating at 50 kV and 20 mA using Mo Ka radiation
˚
(k = 0.71073 A). Data collection at 293 K and reduction
was performed using the SMART and SAINT software [30].
An empirical absorption correction (SADABS) was applied
to the raw intensities [31]. The crystal structure was
determined by direct methods and refined by full-matrix
least-squares using the SHELXTL-PC program package [32].
Non-hydrogen atoms were subjected to anisotropic refine-
ment. All hydrogen atoms were generated geometrically
4.3. General procedure for synthesis of N-substituted
benzylidene-4-ferrocenyl-5-(1H-1,2,4-triazol-1-yl)-1,3-
thiazol-2-amine (5a–q)
˚
(C–H lengths fixed at 0.93 A), assigned appropriate isotro-
2-Amino-4-ferrocenyl-5-(1H-1,2,4-triazol-1-yl)-1,3-thia-
zole (0.35 g, 1 mmol) and substituted benzaldehyde
(1 mmol) were dissolved in 10 mL of benzene. One drop
pic thermal parameters, and included in structure factor
calculations in the final stage of F2 refinement. A summary
of the crystal data is given in Table 5.
Acknowledgements
Table 5
Crystallographic data for compound 5a
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.
Empirical formula
Crystal system
Space group
C22H17FeN5S
Triclinic
P-1
Unit cell dimensions
˚
a (A)
8.826 (4)
10.608 (5)
11.619 (5)
˚
b (A)
References
˚
c (A)
a (ꢁ)
b (ꢁ)
c (ꢁ)
64.982 (7)
83.064 (8)
83.064 (8)
976.0 (8)
[1] J.V. Metzger, The chemistry of heterocyclic compounds, in: Thiazole
and Its DerivativesA Series of Monographs, vol. 34, Wiley, Chich-
ester, 1979.
[2] B. Dash, S. Praharaj, P.K. Mohapatra, J. Indian Chem. Soc. LVIII
(1981) 1184.
[3] H.D. Troutman, L.M. Long, J. Am. Chem. Soc. 70 (1948) 3436.
[4] B. Dash, M. Patra, S. Praharaj, Indian J. Chem. 19B (1980) 894.
[5] B. Dash, P.K. Mahapatra, D. Panda, J.M. Pattnaik, J. Indian Chem.
Soc. LXI (1984) 1061.
[6] N. Motohashi, R. Meyer, S.R. Gollapudi, J. Organometal. Chem.
205 (1990) 398.
[7] E.L. Michelotti, D.P. Le, G.R. Carlson, A.R. Egan, US Patent 5
075471, 1991.
[8] L. Chen, Q.M. Wang, R.Q. Huang, C.H. Mao, J. Shang, H.B. Song,
Appl. Organometal. Chem. 19 (2005) 45.
[9] L. Chen, Q.L. Xie, L.J. Sun, H.L. Wang, J. Organometal. Chem. 678
(2003) 90.
[10] L . Chen, J.X. Chen, L.J. Sun, Q.L. Xie, Appl. Organometal. Chem.
19 (2005) 1038.
3
˚
V (A )
Z
2
Dcalc (mg mmÀ3
Absorption coefficient (mmÀ1
F (000)
Crystal size (mmÀ3
h Range for data collection (ꢁ)
Limiting indices
)
1.495
0.898
452
)
)
0.22 · 0.20 · 0.18
1.94–25.01
À10 6 h 6 8,
À12 6 k 6 12,
À11 6 l 6 13
4998
3425 (Rint = 0.0245)
99.3%
1.038
Reflections collected
Independent reflections
Completeness to h = 25.01
Goodness-of-fit
Final R indices [I > 2r (I )]
R indices (all data)
R1 = 0.0381, wR2 = 0.0904
R1 = 0.0588, wR2 = 0.1029
0.266 and À0.257
Large differenceÀp3eak
[11] X.Q. Song, Z.Q. Yang, Q.L. Xie, J. Organometal. Chem. 103 (1998)
566.
˚
and hole (e A
)

996
H. Yu et al. / Journal of Organometallic Chemistry 692 (2007) 991–996
[12] H.K. Sun, Q.M. Wang, R.Q. Huang, J. Organometal. Chem. 182
[22] L.C. King, R.J. Hlavacek, J. Am. Chem. Soc. 72 (1950) 3722.
[23] A.A. Monton, H.P. Penner, J. Am. Chem. Soc. 73 (1951) 3300.
[24] V.K. Gewald, H. Bottcher, R. Mayer, J. Prakt. Chem. 23 (1964) 298.
[25] R. Dahiya, H.K. Pujari, Indian J. Chem. Sect. B 25 (1986) 966.
[26] R.M. Moriarty, B.K. Vaid, M.P. Duncan, S.G. Levy, O. Prakash, S.
Goyal, Synthesis (1992) 845.
(2002) 655.
[13] H. Buchenauer, Proc. Br. Crop. Protect. Conf. 2 (1977) 699.
[14] H. Buchenauer, J. Plant. Dis. Protect. (Z. Pflanzenkr. Pflanzenschutz)
10 (1979) 341.
[15] Z. Jin, Y. Hu, A.H. Huo, W.F. Tao, L. Shao, J.B. Liu, J.X. Fang, J.
Organomet. Chem. 691 (2006) 2340.
[27] E.B. Knot, J. Chem. Soc. (1947) 1656.
[16] J.B. Liu, L.C. Li, H. Dai, Z. Liu, J.X. Fang, J. Organomet. Chem.
691 (2006) 2686.
[28] H.B. Yu, L. Shao, Z. Jin, J.B. Liu, J.X. Fang, Acta Crystallogr.,
Sect. E 61 (2005) m2031.
[17] J.X. Fang, Z. Jin, Z.M. Li, W. Liu, J. Organomet. Chem. 674 (2003)
1.
[18] J.X. Fang, Z. Jin, Z.M. Li, W. Liu, Appl. Organometal. Chem. 17
(2003) 145.
[29] J.C. Kapteyn, J.B. Pillmoor, M.A. De Waard, Pest. Sci. 34 (1992) 37.
[30] SMART 5.0 and Saint 4.0 for windows NT: Area Detector Control
and Integration Software, Bruker Analytical X-ray Systems, Inc.,
Madison, WI, 1998.
[19] C. Biot, L. Delhaes, H. Abessolo, J. Organomet. Chem. 59 (1999)
589.
[20] C. Biot, J. Med. Chem. 35 (2000) 707.
[31] G.M. Sheldrick, SADABS: program for empirical absorption correction
of area detector data, University of Go¨ttingen, Germany, 1996.
[32] G.M. Sheldrick, SHELXTL 5.10 for Windows NT: structure determi-
nation software programs, Bruker Analytical X-ray Systems, Inc.,
Madison, WI, 1997.
´
[21] A. Tarraga, P. Molina, D. Curiel, J.L. Lo’pez, M.D. Velasco,
Tetrahedron 55 (1999) 14701.