Synthesis and Antifungal Activity of 3-substituted 5-ferrocenyl-1H-pyrazoles

Article abstract of DOI:10.1007/s10593-018-2379-7

[Figure not available: see fulltext.] A convenient method for the selective synthesis of functionalized 3-substituted 5-ferrocenyl-1H-pyrazoles has been developed. Condensation reaction of α,β-unsaturated ferrocenyl ketones and tosylhydrazine in the presence of catalytic amount of iron(III) phthalocyanine chloride allowed to obtain nine new 3-substituted 5-ferrocenyl-1H-pyrazoles. The synthesized products were evaluated for their antifungal activity against Gibberella nicotiancola, Fusarium oxysporum f. sp. niveum, and Gibberella saubinetii. Most of the compounds exhibited excellent antifungal activity.

Full text of DOI:10.1007/s10593-018-2379-7

DOI 10.1007/s10593-018-2379-7
Chemistry of Heterocyclic Compounds 2018, 54(10), 951–955
Synthesis and antifungal activity
of 3-substituted 5-ferrocenyl-1H-pyrazoles
Man Ge1,2, Hailian Huang1, Xiaofeng Gou1,
Chengwen Hua1, Bang Chen1, Junlong Zhao1*
1 Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education,
College of Chemistry & Materials Science, Northwest University,
1 Xuefu Ave., Guodu, Chang'an District, Xi'an, Shaanxi 710127, China;
e-mail: zhaojunlong327@163.com
2 College of Science, Xi'an University of Architecture and Technology,
13 Yanta Rd., Xi'an, Shaanxi 710055, China; e-mail: 2447196@qq.com
Published in Khimiya Geterotsiklicheskikh Soedinenii,
2018, 54(10), 951–955
Submitted July 26, 2018
Accepted August 28, 2018
O
N
HN
1. NH2NHTs
EtOH, 60°C, 56 h
Ar
Ar
Fe
Fe
2. Fe(III) phthalocyanine chloride
(6 mol %)
K2CO3, EtOH, , 5 h
5364%
9 examples
Antifungal activity against: Gibberella nicotiancola
Fusarium oxysporum f. sp. niveum
Gibberella saubinetii
Ar = Ph, 4-MeOC6H4, 4-ClC6H4, 4-FC6H4, 4-O2NC6H4, 3-O2NC6H4,
3-BrC6H4, 2,4-Cl2C6H3, thiophen-2-yl
A convenient method for the selective synthesis of functionalized 3-substituted 5-ferrocenyl-1H-pyrazoles has been developed.
Condensation reaction of α,β-unsaturated ferrocenyl ketones and tosylhydrazine in the presence of catalytic amount of iron(III) phthalo-
cyanine chloride allowed to obtain nine new 3-substituted 5-ferrocenyl-1H-pyrazoles. The synthesized products were evaluated for their
antifungal activity against Gibberella nicotiancola, Fusarium oxysporum f. sp. niveum, and Gibberella saubinetii. Most of the
compounds exhibited excellent antifungal activity.
Keywords: ferrocene, iron(III) phthalocyanine chloride, pyrazole, antifungal activity.
Pyrazoles have attracted a great deal of attention as
valuable building blocks for agrochemicals possessing
antifungal,1 herbicidal,2 and insecticidal3 activities. For
example, furametpyr has been used to control rice sheath
blight, whereas penthiopyrad has been effective against
strobilurin- and DMI-resistant plant diseases (Fig. 1).4 In
addition, antitumor,5 analgesic,6 and anti-inflammatory7
activities of compounds bearing pyrazole scaffold have
been also demonstrated.
ferrocene core have displayed antifungal,10 herbicidal,11
antitumor,12 antimalarial,13 and anti-inflammatory14 activi-
ties. Furthermore, ferrocene-conjugated ruthenium(II)
complexes have attracted attention as promising DNA
cleaving agents.15 The aforementioned considerations
encouraged us to anticipate that integration of a ferrocenyl
It has already been shown that incorporation of a
ferrocene fragment into an organic compound represents a
significant strategy to increase both biological activity and
safety. Ferrocene derivatives8 exhibit a variety of important
properties, including hydrophobicity, low toxicity, and
good overall stability.9 Several compounds containing
Figure 1. Pyrazole-based compounds with antifungal activity.
0009-3122/18/54(10)-0951©2018 Springer Science+Business Media, LLC
951

Chemistry of Heterocyclic Compounds 2018, 54(10), 951–955
Scheme 1
group into structurally different pyrazoles would improve
their biological activities. Herein, we report the synthesis of
a number of 3-substituted 5-ferrocenyl-1H-pyrazoles as
novel antifungal agents. The antifungal properties have
been examined in vitro, and the relationship between the
structures of products and their biological activity has been
explored.
On the basis of the previous studies,16a,b we have
developed a strategy for the synthesis of 3,5-disubstituted
1H-pyrazoles using α,β-unsaturated ketones, N2H4·H2O,
and iron(III) phthalocyanine chloride as a recyclable
catalyst.16c However, further attempts to obtain 3-substituted
5-ferrocenyl-1H-pyrazoles by the same method have proven
unsuccessful. In current work, reaction of α,β-unsaturated
ferrocenyl ketones 1a–i and tosylhydrazine in EtOH was
performed (Scheme 1). Subsequent intramolecular cycliza-
tion was conducted in the presence of K2CO3 and catalytic
amounts of iron(III) phthalocyanine chloride to provide
products 2a–i, bearing various aromatic groups, in
moderate yields (53–64%).
The spatial structure of compound 2g was determined by
X-ray diffraction analysis (Fig. 2). The single crystal was
grown from EtOH at room temperature. The molecular
structure of 3-(3-bromophenyl)-5-ferrocenyl-1H-pyrazole
(2g) is defined by the arrangement of pyrazole, two
cyclopentadienes of the ferrocenyl moiety, and phenyl
group. Steric hindrance between the protons of pyrazole
and ferrocenyl group is minimized by a perpendicular
placement of the pyrazole ring and its substituent
cyclopentadienyl (Cp) group. On the other hand, optimal
electronic overlap of the π-systems of pyrazole and
3-bromophenyl group is achieved by a coplanar arrange-
ment. The dihedral angle of 26.7° between the substituted
Cp ring and the pyrazole ring in compound 2g is in the
range of the respective angles of ferrocenyl-substituted
pyrazoles (8.20–45.36°).17 The C(9)–C(10) bond length of
1.455(4) Å corresponds to that of substituted phenyl
pyrazole derivatives (1.472(3) and 1.4785(19) Å).18 In the
ferrocenyl moiety, the Cp rings are perfectly planar but
slightly deviate from being parallel, possessing 1.53° angle
between the plane normals. The Cg2–Fe(1)–Cg3 angle
(where Cg is the center of the plane defined by five C atoms)
is 179.31°. The distances Cg2–Fe(1) and Cg3–Fe(1) are
1.639(8) and 1.638(8) Å, respectively. The C–C bond
lengths and C–C–C angles in the Cp rings show electronic
overlap of the π-system-induced variations. The longest
mean C–C distance in the Cp ring is C(10)–C(11) and
C(10)–C(14) at 1.414(4) Å. The adjacent C(11)–C(12) and
C(14)–C(13) bonds are 1.401(4) and 1.406(4) Å, respec-
tively. Finally, the C(12)–C(13) bond length is 1.397(5) Å.
Figure 2. The molecular structure of compound 2g with atoms
represented by thermal vibration ellipsoids of 50% probability.
The C(11)–C(10)–C(14) angle averages 107.6(2)°, a slightly
reduced value from the ideal 108°. The other angles in
Cp ring average 108.1°. Among all Fe(1)–C distances,
Fe(1)–C(10) is the longest (mean value 2.034(4) Å).
In continuation of this research, antifungal activity of the
synthesized 3-substituted 5-ferrocenyl-1H-pyrazoles 2a–i
was evaluated and expressed as inhibition ratio (Table 1).
According to the results, compounds 2a–i exhibited certain
activity against fungi Gibberella nicotiancola, Fusarium
oxysporum f. sp. niveum, and Gibberella saubinetii at a
concentration of 125 μg/ml. Compared to a previously
reported fungicide pyraclostrobin,19 which provided
inhibition ratio of 36.9% against Gibberella nicotiancola and
Fusarium oxysporum f. sp. niveum, 5-ferrocenyl-3-(3-nitro-
phenyl)-1H-pyrazole (2f) and 3-(3-bromophenyl)-5-fer-
rocenyl-1H-pyrazole (2g) exhibited significantly higher
inhibition ratio against Gibberella nicotiancola (entry 10 vs
entries 6, 7). Furthermore, 5-ferrocenyl-3-phenyl-1H-
Table 1. Antifungal activity of 3-substituted
5-ferrocenyl-1H-pyrazoles 2a–i and pyraclostrobin
Inhibition ratio**, %
Fusarium
Entry Compound*
Gibberella
nicotiancola
Gibberella
saubinetii
oxysporum f. sp.
niveum
1
2
3
4
5
6
7
8
9
35.5
57.1
32.5
38.6
15.2
84.9
74.0
52.5
67.1
36.9
72.8
45.7
46.9
49.4
30.5
51.0
46.1
43.2
58.0
36.9
38.3
58.5
51.7
8.3
55.2
26.8
37.9
26.9
27.2
65.6
2a
2b
2c
2d
2e
2f
2g
2h
2i
10 Pyraclostrobin
* Concentration of compounds 2a–i 125 μg/ml.
** Mean value of three measurements.
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Chemistry of Heterocyclic Compounds 2018, 54(10), 951–955
pyrazole (2a) displayed the highest inhibition rate against
as 0.016 μg/ml for Gibberella nicotiancola and slightly
higher for Fusarium oxysporum f. sp. niveum than EC50 of
pyraclostrobin (entry 6 vs entry 10). However, 5-ferrocenyl-
3-(4-methoxyphenyl)-1H-pyrazole (2b) displayed higher
antifungal activity against all three fungi strains Gibberella
nicotiancola, Fusarium oxysporum f. sp. niveum, and
Gibberella saubinetii with EC50 values of 0.078, 0.158, and
0.068 μg/ml, compared to pyraclostrobin with EC50 values
of 0.226, 0.223, and 0.153 μg/ml, respectively (entry 2 vs
entry 10). Therefore, compound 2b was distinguished as
the most promising candidate for development of a new
antifungal agent.
In summary, a simple, green, and efficient synthesis of
3-substituted 5-ferrocenyl-1H-pyrazoles using iron(III)
phthalocyanine chloride as a catalyst has been developed.
The reaction system tolerated various functional groups
and provided the desired products in moderate yields. Nine
pyrazole derivatives were successfully prepared and their
antifungal activity was tested. All of the investigated
compounds exhibited significant antifungal activity against
Gibberella nicotiancola, Fusarium oxysporum f. sp. niveum,
and Gibberella saubinetii. From a structure–activity
relationship point of view, introduction of a ferrocenyl group
into the pyrazole skeleton contributed more to antifungal
activity of the target compounds than variation of the
aromatic group. 3-Substituted 5-ferrocenyl-1H-pyrazoles
possessing 4-methoxyphenyl, 3-nitrophenyl, 3-bromo-
phenyl, 2,4-dichlorophenyl, and 2-thienyl groups demon-
strated an improved inhibition against Gibberella nicotiancola
and Fusarium oxysporum f. sp. niveum. Among these
compounds, 5-ferrocenyl-3-(4-methoxyphenyl)-1H-pyrazole
demonstrated increased antifungal activity against all three
tested fungi strains Gibberella nicotiancola, Fusarium
oxysporum f. sp. niveum, and Gibberella saubinetii.
Fusarium oxysporum f. sp. niveum (entry 1). In terms of
structure–activity relationship, 3-substituted 5-ferrocenyl-
1H-pyrazoles 2a–i showed higher antifungal activity
against Gibberella nicotiancola and Fusarium oxysporum
f. sp. niveum than the broad spectrum antifungal agent
pyraclostrobin.
In addition to the inhibition ratio, EC50 and EC95 values
of compounds 2a–i and pyraclostrobin were also
determined (Table 2). Most of the compounds were more
active against Gibberella nicotiancola and Fusarium
oxysporum f. sp. niveum. 3-(4-Chlorophenyl)-5-ferrocenyl-
1H-pyrazole (2c) exhibited noteworthy antifungal activity
against both Fusarium oxysporum f. sp. niveum and
Gibberella saubinetii (entry 3). The EC50 value of
5-ferrocenyl-3-(3-nitrophenyl)-1H-pyrazole (2f) was as low
Table 2. EC50 and EC95 of 3-substituted
5-ferrocenyl-1H-pyrazoles 2a–i and pyraclostrobin
EC50*, EC95*,
μg/ml μg/ml
Entry Compound
Fungal strain
1
2
3
4
5
6
7
8
9
Gibberella nicotiancola
0.300 14.437
2a
2b
2c
2d
2e
2f
Fusarium oxysporum f. sp. niveum 0.020 43.753
Gibberella saubinetii
0.256 13.274
0.078 5.421
Gibberella nicotiancola
Fusarium oxysporum f. sp. niveum 0.158 6.100
Gibberella saubinetii
0.068 6.807
0.329 11.173
Gibberella nicotiancola
Fusarium oxysporum f. sp. niveum 0.149 5.945
Gibberella saubinetii
0.113 6.223
0.266 19.341
Gibberella nicotiancola
Fusarium oxysporum f. sp. niveum 0.129 4.638
Experimental
Gibberella saubinetii
0.835 7.963
0.619 7.942
IR spectra were recorded on a Bruker Equinox 55 FT-IR
spectrometer in KBr pellets. 1H and 13C NMR spectra were
recorded on a Bruker AMX 400 NMR spectrometer (400
and 100 MHz, respectively) using DMSO-d6 (compounds
2a,d–i) and CDCl3 (compounds 2b,c) as the solvents. The
13C NMR spectrum of compound 2a was obtained in a
mixture of DMSO-d6 and CDCl3. HRMS analyses were
carried out on a Bruker micrOTOF-Q II instrument
(electrospray ionization). Melting points were determined
on a XD-4 micro-melting point apparatus and are uncor-
rected. The reaction progress was monitored by TLC on
Shenghai silica gel plates, and visualization was performed
using UV light. All reagents were purchased from
commercial suppliers and were used without further
purification.
Synthesis of 3-substituted 5-ferrocenyl-1H-pyrazoles
2a–i (General method). A solution of α,β-unsaturated
ferrocenyl ketone 1a–i (3 mmol) and tosylhydrazine
(670 mg, 3.6 mmol) in EtOH (25 ml) was stirred at 60°C
for 5–6 h, and the reaction progress was monitored by TLC
(eluent petroleum ether – EtOAc, 3:1). Upon completion of
the reaction, the solution was cooled to room temperature,
K2CO3 (829 mg, 6 mmol) and iron(III) phthalocyanine
Gibberella nicotiancola
Fusarium oxysporum f. sp. niveum 0.462 31.185
Gibberella saubinetii
0.096 2.503
0.016 0.421
Gibberella nicotiancola
Fusarium oxysporum f. sp. niveum 0.101 3.284
Gibberella saubinetii
0.291 2.740
0.023 1.766
Gibberella nicotiancola
2g
2h
2i
Fusarium oxysporum f. sp. niveum 0.144 1.718
Gibberella saubinetii
0.218 4.214
0.107 5.568
Gibberella nicotiancola
Fusarium oxysporum f. sp. niveum 0.139 6.274
Gibberella saubinetii
0.288 2.667
0.055 1.170
Gibberella nicotiancola
Fusarium oxysporum f. sp. niveum 0.084 2.149
Gibberella saubinetii
10 PyraclostrobinGibberella nicotiancola
0.338 5.015
0.226 4.131
Fusarium oxysporum f. sp. niveum 0.223 3.798
Gibberella saubinetii
0.153 1.782
* Mean value of three measurements.
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Chemistry of Heterocyclic Compounds 2018, 54(10), 951–955
chloride (109 mg, 6 mol %) were added, and the mixture
5-Ferrocenyl-3-(3-nitrophenyl)-1H-pyrazole (2f). Yield
606 mg (54%), red solid, mp 195–196°C. IR spectrum,
ν, cm–1: 3432, 3242, 2923, 1603, 1535, 1506, 1461, 1345,
1165, 1064, 980, 863, 821, 789, 737, 665. 1H NMR
spectrum, δ, ppm (J, Hz): 4.10 (5H, s, C5H5); 4.36 (2H, s,
C5H4); 4.82 (2H, s, C5H4); 7.04 (1H, s, =CH); 7.74 (1H,
br. s, H Ar); 8.17 (1H, d, J = 8.0, H Ar); 8.29 (1H, d, J = 8.0,
H Ar); 8.64 (1H, br. s, H Ar); 13.24 (1H, s, NH). 13C NMR
spectrum, δ, ppm: 66.7; 69.2; 69.9; 74.2; 100.0; 120.0;
122.3; 126.1; 128.0; 130.7; 131.7; 136.0; 143.7; 148.8.
Found, m/z: 374.0592 [M+H]+. C19H16FeN3O2. Calculated, m/z:
374.0592.
was refluxed for 5 h. The obtained precipitate was filtered
off and the filtrate was extracted with EtOAc (3×25 ml).
The combined organic layers were washed with brine (25 ml)
and dried over anhydrous Na2SO4. The solvent was
evaporated under reduced pressure, and crude product 2a–i
was purified by column chromatography (silica gel, eluent
petroleum ether – EtOAc, 9:1).
5-Ferrocenyl-3-phenyl-1H-pyrazole (2a). Yield 632 mg
(64%), red solid, mp 261–263°C. IR spectrum, ν, cm–1:
3427, 2922, 1598, 1454, 1354, 1169, 1038, 816, 666.
1H NMR spectrum, δ, ppm (J, Hz): 4.09 (5H, s, C5H5); 4.35
(2H, s, C5H4); 4.78 (2H, s, C5H4); 6.80 (1H, s, =CH); 7.30
(1H, t, J = 7.2, H Ar); 7.41 (2H, t, J = 7.6, H Ar); 7.83 (2H,
d, J = 7.5, H Ar); 12.94 (1H, s, NH). 13C NMR spectrum,
δ, ppm: 66.6; 69.1; 69.9; 74.7; 99.3; 125.5; 127.7; 129.0;
134.3; 142.9; 151.1. Found, m/z: 329.0727 [M+H]+.
C19H17FeN2. Calculated, m/z: 329.0741.
3-(3-Bromophenyl)-5-ferrocenyl-1H-pyrazole (2g). Yield
781 mg (64%), red solid, mp 155–157°C. IR spectrum,
ν, cm–1: 3426, 2920, 1597, 1565, 1456, 1173, 1105, 1064,
1
997, 818, 779, 683. H NMR spectrum, δ, ppm (J, Hz):
4.09 (5H, s, C5H5); 4.35 (2H, s, C5H4); 4.79 (2H, s, C5H4);
6.90 (1H, s, =CH); 7.40 (1H, d, J = 8.0, H Ar); 7.49 (1H, d,
J = 8.0, H Ar); 7.86 (1H, s, H Ar); 8.03 (1H, s, H Ar);
13.08 (1H, s, NH). 13C NMR spectrum, δ, ppm: 66.6; 69.1;
69.9; 74.4; 99.7; 122.6; 124.4; 127.9; 130.3; 131.3; 136.7;
143.3; 149.7. Found, m/z: 406.9838 [M+H]+. C19H16BrFeN2.
Calculated, m/z: 406.9846.
5-Ferrocenyl-3-(4-methoxyphenyl)-1H-pyrazole (2b).
Yield 646 mg (60%), red solid, mp 175–176°C. IR spectrum,
ν, cm–1: 3441, 2922, 1615, 1509, 1433, 1251, 1172, 1033,
1
988, 830, 664, 617. H NMR spectrum, δ, ppm: 3.83 (3H,
s, OCH3); 4.08 (5H, s, C5H5); 4.28 (2H, s, C5H4); 4.63 (2H,
s, C5H4); 6.51 (1H, s, =CH); 6.92 (2H, br. s, H Ar); 7.69
(2H, br. s, H Ar). 13C NMR spectrum, δ, ppm: 55.4; 66.6;
68.8; 69.7; 75.6; 99.5; 114.2; 124.7; 127.0; 128.9; 131.0;
159.6. Found, m/z: 359.0843 [M+H]+. C20H19FeN2O.
Calculated, m/z: 359.0847.
3-(2,4-Dichlorophenyl)-5-ferrocenyl-1H-pyrazole (2h).
Yield 750 mg (63%), red solid, mp 120–121°C. IR spectrum,
ν, cm–1: 3435, 2919, 1650, 1586, 1469, 1441, 1384, 1168,
1105, 1003, 955, 820, 800, 661. 1H NMR spectrum, δ, ppm
(J, Hz): 4.08 (5H, s, C5H5); 4.34 (2H, s, C5H4); 4.79 (2H, s,
C5H4); 6.84 (1H, s, =CH); 7.48 (1H, d, J = 8.0, H Ar); 7.67
(1H, s, H Ar); 7.90 (1H, d, J = 8.0, H Ar); 13.22 (1H, s,
NH). 13C NMR spectrum, δ, ppm: 66.7; 69.1; 69.9; 74.4;
103.0; 127.9; 130.1; 131.9; 132.0; 132.2; 132.9; 142.4;
147.8. Found, m/z: 396.9970 [M+H]+. C19H15Cl2FeN2.
Calculated, m/z: 396.9962.
3-(4-Chlorophenyl)-5-ferrocenyl-1H-pyrazole
(2c).
Yield 664 mg (61%), red solid, mp 117–178°C, IR spectrum,
ν, cm–1: 3444, 2919, 1641, 1490, 1444, 1352, 1168, 1090,
1
1012, 962, 815, 665. H NMR spectrum, δ, ppm (J, Hz):
4.11 (5H, s, C5H5); 4.32 (2H, s, C5H4); 4.61 (2H, s, C5H4);
6.57 (1H, s, =CH); 7.38 (2H, d, J = 8.0, H Ar); 7.72 (2H, d,
J = 8.0, H Ar). 13C NMR spectrum, δ, ppm: 65.6; 66.6;
69.2; 69.6; 69.8; 74.2; 99.6; 127.1; 128.9; 131.0; 133.9;
141.5; 149.9. Found, m/z: 363.0347 [M+H]+. C19H16ClFeN2.
Calculated, m/z: 363.0351.
5-Ferrocenyl-3-(thiophen-2-yl)-1H-pyrazole (2i). Yield
533 mg (53%), red solid, mp 195–198°C. IR spectrum,
ν, cm–1: 3413, 2928, 2836, 1613, 1512, 1439, 1301, 1251,
1
1169, 1105, 1031, 818, 675. H NMR spectrum, δ, ppm
5-Ferrocenyl-3-(4-fluorophenyl)-1H-pyrazole
(2d).
(J, Hz): 4.08 (5H, s, C5H5); 4.34 (2H, s, C5H4); 4.78 (2H, s,
C5H4); 6.67 (1H, s, =CH); 7.09 (1H, s, H Ar); 7.43 (2H, d,
J = 4.0, J = 2.6, H Ar); 12.89 (1H, s, NH). 13C NMR
spectrum, δ, ppm: 66.6; 69.1; 69.9; 74.3; 99.1; 123.8; 124.8;
128.0; 137.7; 143.1; 146.8. Found, m/z: 335.0301 [M+H]+.
C17H15FeN2S. Calculated, m/z: 335.0305.
Yield 656 mg (63%), red solid, mp 118–120°C. IR spectrum,
ν, cm–1: 3404, 2922, 1647, 1598, 1509, 1411, 1320, 1224,
1
1170, 1106, 1039, 913, 814, 707, 668. H NMR spectrum,
δ, ppm (J, Hz): 4.08 (5H, s, C5H5); 4.32 (2H, s, C5H4); 4.77
(2H, s, C5H4); 6.79 (1H, s, =CH); 7.26 (2H, d, J = 6.9,
H Ar); 7.86 (2H, br. s, H Ar); 12.94 (1H, s, NH). 13C NMR
spectrum, δ, ppm (J, Hz): 66.7; 69.1; 69.9; 74.4; 103.0;
127.9; 130.1; 132.0 (d, JCF = 25); 132.9; 142.4; 147.7.
Found, m/z: 347.0641 [M+H]+. C19H16FFeN2. Calculated,
m/z: 347.0647.
5-Ferrocenyl-3-(4-nitrophenyl)-1H-pyrazole (2e). Yield
628 mg (56%), red solid, mp 239–241°C. IR spectrum, ν, cm–1:
3443, 3230, 2923, 1601, 1513, 1410, 1337, 1171, 1105,
1035, 960, 853, 821, 803, 756, 670. 1H NMR spectrum, δ, ppm
(J, Hz): 4.09 (5H, s, C5H5); 4.36 (2H, s, C5H4); 4.80 (2H, s,
C5H4); 7.01 (1H, s, =CH); 8.10 (2H, d, J = 8.7, H Ar); 8.29
(2H, d, J = 8.7, H Ar); 13.31 (1H, s, NH). 13C NMR
spectrum, δ, ppm: 66.7; 69.3; 69.9; 74.1; 100.7; 124.6;
126.2; 140.8; 143.8; 146.7; 149.2. Found, m/z: 374.0583
[M+H]+. C19H16FeN3O2. Calculated, m/z: 374.0592.
X-ray structural study of compound 2g. Single crystal
X-ray crystallographic data were recorded on a Bruker
SMART APEX II CCD diffractometer with graphite-
monochromated MoKα radiation (λ 0.71073 Å) at room
temperature. The crystal structures were solved by direct
methods and refined by full-matrix least-squares method.
The complete crystallographic dataset was deposited at the
Cambridge Crystallographic Data Center (deposit
CCDC 1868442).
Antifungal activity assay. The antifungal activity of
compounds 2a–i was evaluated in vitro against three fungi
strains – Gibberella nicotiancola, Fusarium oxysporum f. sp.
niveum, and Gibberella saubinetii. Solution of each
compound in DMF (50 mg/ml) was added to sterilized
potato dextrose agar (PDA) to generate a series of dilutions
954

Chemistry of Heterocyclic Compounds 2018, 54(10), 951–955
5754. (b) Tessmann, J. W.; Buss, J.; Begnini, K. R.;
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separately transferred to the Petri dishes containing compounds
2a–i in PDA and incubated at 28°C for 3 days after
solidification. Each experiment was carried out in triplicates.
Pyraclostrobin was used as a positive control, and DMF served
as a negative control. The colony diameter of each strain was
measured by cross bracketing method. The antifungal activity
was expressed as inhibition ratio (Equation (1)).
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Inhibition ratio = (Cd – Td)/(Cd – 4) × 100%,
(1)
where Cd – fungal colony diameter on the control PDA-
based plate, mm and Td – fungal colony diameter on the
treatment PDA-based plate, mm.
1
The Supplementary information file, containing H and
13C NMR spectroscopic data of compounds 2a–i and results
of X-ray crystallographic analysis of compound 2g, is
available at the journal website at http://link.springer.com/
journal/10593.
The financial support by the National Natural Science
Foundation of China (project 21703171), the Foundation
of Shaanxi Educational Committee (project 2013JK0975),
and the Natural Science Basic Research Plan in Shaanxi
Province of China (project 2018JQ2043) is gratefully
acknowledged.
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