Synthesis and antifungal activities of New pyrazole derivatives via 1,3-dipolar cycloaddition reaction

Article abstract of DOI:10.1111/j.1747-0285.2010.00948.x

A series of cycloadducts - pyrazoles via 1,3-dipolar cycloaddition reactions of generated nitrilimines with N-(4-chloro-2-fluorophenyl)maleimide were described. The novel compounds synthesized were characterized by ¹H NMR, MS, and elemental analysis. The fungicidal tests showed that most of the title compounds exhibit significant fungicidal activities against Corynespora cassiicola.

Full text of DOI:10.1111/j.1747-0285.2010.00948.x

ª 2010 John Wiley & Sons A/S
doi: 10.1111/j.1747-0285.2010.00948.x
Chem Biol Drug Des 2010; 75: 489–493
Research Article
Synthesis and Antifungal Activities of New
Pyrazole Derivatives via 1,3-dipolar
Cycloaddition Reaction
were also tested. In our experiments, the nitrile imine dipole gener-
Chuan-Yu Zhang, Xing-Hai Liu, Bao-Lei
Wang*, Su-Hua Wang, Zheng-Ming Li*
ated by a-halohydrazones with base can be used directly without
isolating and reacted with dipolarophiles to give the title com-
pounds, and the yield of the title compounds is relatively higher
than that of 2,4,7-triphenyl-6,8-dioxo-2,3,7-triazabicyclo(3.3.0)oct-
3-ene generated by analogous reaction of phenylhydrazones with
N-phenylmaleimide (20).
State Key Laboratory of Elemento-Organic Chemistry, Nankai
University, Tianjin 300071, China
*Corresponding authors: Zheng-Ming Li,nkzml@vip.163.com and
Bao-Lei Wang, wangbaolei@126.com
A series of cycloadducts–pyrazoles via 1,3-dipolar
cycloaddition reactions of generated nitrilimines
with N-(4-chloro-2-fluorophenyl)maleimide were
described. The novel compounds synthesized were
characterized by 1H NMR, MS, and elemental anal-
ysis. The fungicidal tests showed that most of the
title compounds exhibit significant fungicidal
activities against Corynespora cassiicola.
Experimental
Instruments
Melting points were determined using an X-4 apparatus (Taike, Beij-
ing, China) and were uncorrected. H NMR spectra were measured
1
on a Bruker AC-P500 instrument (300 MHz, Bruker, Fallanden, Swit-
zerland) using TMS as an internal standard and DMSO-d6 as sol-
vent. Mass spectra were recorded on a Thermo Finnigan LCQ
Advantage LC ⁄ mass detector instrument (Thermo-Finnigan, MA,
USA). Elemental analysis was performed on a Vario EL elemental
analyzer (Elementar, Hanau, Germany).
Key words: 1,3-dipolar cycloaddition, antifungal activities, pyrazole
derivatives, synthesis
Received 5 May 2009, revised 30 December 2009 and accepted for pub-
lication 31 December 2009
Synthesis of compounds
Nitrogen-linked heterocyclic compounds received considerable atten-
tion in recent times because of their medicinal and pesticidal impor-
tance (1–3). It is well known that the study of pyrazole derivatives is
significant in pesticide chemistry, and some of the pyrazole deriva-
tives were widely used because of their antiviral (4), antitumor (5),
anti-inflammatory (6), antibacterial (7), herbicidal (8), insecticidal (9),
and fungicidal activities (10). It was also found that the o-phthalimide
nucleus, which incorporates a pyrazole ring, exhibits a large number
of biological activities, especially herbicidal activities.a In addition,
many biological compounds contain a fluoro moiety, which indicates
that this moiety may be important for biological activity (11).
The synthetic route was shown in Scheme 1. The yields of com-
pounds were not optimized. Intermediate 1-(4-chloro-2-fluorophenyl)-
1H-pyrrole-2,5-dione was synthesized according to the reference (21).
Benzoyl chloride (2a) (22). Benzoic acid (1a, 3.66 g, 30 mmol) was
placed in a 100-ml round-bottomed flask, and SOCl2 (4.43 g,
37.5 mmol) was added dropwise with stirring. The mixture was
heated gently for 1 h at 100 ꢀC (10 mL SOCl2 was added after
20 min to make a clear solution), cooled, and then distilled (70 ꢀC)
at atmospheric pressure to remove excess SOCl2. A vacuum was
applied, and the bath temperature was slowly increased to 100 ꢀC
to give one fraction of 2a (3.4 g, 81%) as a colorless liquid.
Among various synthetic methods to prepare pyrazolines, 1,3-dipolar
cycloaddition between nitrile imine dipoles and alkene dipolaro-
philes is particularly attractive because of the high regioselectivity
and broad functional group tolerance (12,13). The nitrile imine
dipole can be generated either by treating a-halohy drazones
with base (14–16) or by subjecting tetrazole precursors to heating
(17–19). In continuation of our research on the synthesis of biologi-
cal heterocyclic compounds, a series of new pyrazole derivatives
were synthesized via 1,3-dipolar cycloaddition reactions because of
the convenient and simple procedures, and their antifungal activities
Benzoyl phenylhydrazine (3a) (23). To a stirred solution of 2.16 g
(20 mmol) phenylhydrazine in 20 mL dichloromethane was slowly
added pyridine (1.58 g, 20 mmol) under the ice bath. Then, to this,
well-stirred reaction mixture was added dropwise a solution of ben-
zoyl chloride (2.8 g, 20 mmol) in dichloromethane (5 mL) over a period
of 2 h. Upon completion of addition, ice bath was taken away, and
the stirring was continued for another 3 h at the room temperature. A
solid was collected by filtration, washed with water, dried, and recrys-
tallized with ethanol to give 3.6 g of compound 3a (yield 85%).
489

Zhang et al.
Scheme 1: The synthetic route of title compounds.
a-Chlorobenzaldehyde phenylhydrazones (4a) (24). Carbon tetrachlo-
ride (1.46 mL, 15 mmol) was added to a stirred suspension of com-
pound benzoyl phenylhydrazine (3.18 g, 15 mmol) and Ph3P (4.91 g,
18.75 mmol) in acetonitrile (40 mL). Upon completion of addition,
the reaction mixture was stirred at room temperature for 6 h, and
then the solution was cooled, crystallization was initiated by
scratching, and the crude product was filtered off. Compound
a-chlorobenzaldehyde phenylhydrazone was thus obtained in 50%
yield.
5-(4-chloro-2-fluorophenyl)-1-phenyl-3-p-tolyl-1a,6a-dihydro-pyrrolo[3,4-
c]pyrazole-4,6-dione (5c). White crystal, 54.3% yield; m. p. 211–
212 ꢀC; 1H NMR (DMSO-d6, 400 MHz), d: 2.37 (s, ArCH3, 3H),
5.41(s, CHCO, 1H), 5.54 (s, NCHCO, 1H), 6.96 (t, J = 7.2 Hz, ArH,
1H), 7.31 (d, J = 7.6 Hz, ArH, 2H), 7.36 (t, J = 7.6 Hz, ArH, 2H),
7.50 (d, J = 8.0 Hz, ArH, 4H), 7.70 (s, ArH, 1H), 8.92 (d, J = 7.6 Hz,
ArH, 2H). MS (ESI), m ⁄ z: 432 [M-H]), 468[M-H+Cl]), Anal. Calcd.
For C24H17ClFN3O2: C, 66.44; H, 3.95; N, 9.69. Found: C, 66.11; H,
4.03; N, 9.35.
General procedure (Scheme 1): N-(4-chloro-2-fluorophenyl)maleimide
(0.45 g, 2 mmol) and a-chlorobenzaldehyde phenylhydrazone(0.46 g,
2 mmol) were taken in dry benzene (50 mL) and stirred magnetically
at room temperature. To this well-stirred mixture was added dry tri-
ethylamine (0.51 g, 5 mmol) in benzene (5 mL) dropwise over a per-
iod of 30 min, and the stirring was continued for further 5 h.
Generation of nitrilimine was indicated by the precipitation of tri-
ethylamine hydrochloride salt which was filtered off. The filtrate
thus obtained was concentrated, and the residue was purified by
silica-gel column eluted with ethyl acetate ⁄ petroleum ether (volume
ratio 1:5) to give the light yellow product 5a.
5-(4-chloro-2-fluorophenyl)-3-(3-chlorophenyl)-1-phenyl-1a,6a-dihydro-
pyrrolo[3,4-c]pyrazole-4,6-dione (5d). White crystal, 50.0% yield; m.
p. 212–214 ꢀC; 1H NMR (DMSO-d6, 300 MHz), d: 5.49 (s, CHCO,
1H), 5.62 (s, NCHCO, 1H), 6.99 (t, J = 7.5 Hz, ArH, 1H), 7.37 (t,
J = 7.5 Hz, ArH, 2H), 7.48–7.54 (m, ArH, 6H), 7.68–7.72 (m, ArH,
1H), 7.96–7.99 (m, ArH, 1H), 8.04 (s, ArH, 1H). MS (ESI), m ⁄ z: 452
[M-H]), 488[M-H+Cl]), Anal. Calcd. For C23H14Cl2FN3O2: C, 60.81; H,
3.11; N, 9.25. Found: C, 60.59; H, 3.27; N, 9.47.
5-(4-chloro-2-fluorophenyl)-3-((2,4-dichlorophenoxy)methyl)-1-phenyl-1a,
6a-dihydropyrrolo[3,4-c]pyrazole-4,6-dione (5e). White crystal 81.8%
1
yield; m. p. 120–122 ꢀC; H NMR (DMSO-d6, 400 MHz), d:4.94–5.08
5-(4-chloro-2-fluorophenyl)-1,3-diphenyl-1,6a-dihydropyrrolo[3,4-c]pyr-
azole-4,6(3aH,5H)-dione(5a). light yellow crystals, yield 57.3 %; m.
p. 195–196 ꢀC; 1H NMR (DMSO-d6, 300 MHz), d: 5.45 (s, CHCO,
1H), 5.55 (s, NCHCO, 1H), 6.97 (t, J = 7.5 Hz, ArH, 1H), 7.36
(t, J = 7.5 Hz, ArH, 2H), 7.44–7.52 (m, ArH, 7H), 7.69 (s, ArH, 1H),
8.02 (d, J = 7.8 Hz, ArH, 2H). MS Electron Spray Ionization (ESI),
m ⁄ z: 418([M-H])). Anal. Calcd. For C23H15ClFN3O2: C, 65.80; H, 3.60;
N, 10.01. Found: C, 65.80; H, 3.71; N, 10.27.
(m, ArOCH2, 2H), 5.17(s, CHCO, 1H), 5.52 (s, NCHCO, 1H), 6.95 (s,
ArH, 1H), 7.34–7.73 (m, ArH, 10H), MS (ESI), m ⁄ z: 516 [M-H]),
548[M-H+CH3OH]), Anal. Calcd. For C24H15Cl3FN3O3: C, 55.57; H,
2.91; N, 8.10. Found: C, 55.53; H, 3.17; N, 7.80.
5-(4-chloro-2-fluorophenyl)-3-(4-chlorophenyl)-1-phenyl-1a,6a-dihydro-
pyrrolo[3,4-c]pyrazole-4,6-dione (5f). light yellow crystal, 51.5%
1
yield; m. p. 213–215 ꢀC; H NMR (DMSO-d6, 300 MHz), d: 5.46 (s,
CHCO, 1H), 5.58 (s, NCHCO, 1H), 6.97 (t, J = 7.2 Hz, ArH, 1H), 7.36
(t, J = 7.5 Hz, ArH, 2H), 7.50–7.58 (m, ArH, 6H), 7.68–7.72 (m, ArH,
1H), 8.03 (d, J = 8.4 Hz, ArH, 2H). MS (ESI), m ⁄ z: 452 [M-H]),
488[M-H+Cl]), Anal. Calcd. For C23H14Cl2FN3O2: C, 60.81; H, 3.11;
N, 9.25. Found: C, 60.66; H, 3.18; N, 9.43.
5-(4-chloro-2-fluorophenyl)-3-(2-fluorophenyl)-1-phenyl-1a,6a-dihydro-
pyrrolo[3,4-c]pyrazole-4,6-dione (5b). light yellow crystal, 47.6%
1
yield; m. p. 181–183 ꢀC; H NMR (DMSO-d6, 300 MHz), d: 5.43 (s,
CHCO, 1H), 5.57 (s, NCHCO, 1H),6.98 (t, J = 7.2 Hz, ArH, 1H), 7.28–
7.39 (m, ArH, 5H), 7.49 (d, J = 7.8 Hz, ArH, 4H), 7.68 (d, J = 8.1 Hz,
ArH, 1H), 7.95 (t, J = 7.5 Hz, ArH, 1H). MS (ESI), m ⁄ z: 436 [M-H]),
472[M-H+Cl])Anal. Calcd. For C23H14ClF2N3O2: C, 63.09; H, 3.22; N,
9.60. Found: C, 62.81; H, 3.15; N, 9.80.
5-(4-chloro-2-fluorophenyl)-3-(4-fluorophenyl)-1-phenyl-1a,6a-dihydro-
pyrrolo[3,4-c]pyrazole-4,6-dione (5g). light yellow crystal, 61.2%
1
yield; m. p. 193–194 ꢀC; H NMR (DMSO-d6, 400 MHz), d: 5.43 (s,
490
Chem Biol Drug Des 2010; 75: 489–493

Antifungal Activities of New Pyrazole Derivatives
CHCO, 1H) 5.53 (s, NCHCO, 1H), 6.95 (t, J = 7.2 Hz, ArH, 1H), 7.33
(q, J = 6.8 Hz, ArH, 4H), 7.48 (d, J = 8.4 Hz, ArH, 4H), 7.65–7.70
(m, ArH, 1H), 8.05(t, J = 6.0 Hz, ArH,2H). MS (ESI), m ⁄ z: 436 [M-
H]), 472[M-H+Cl]), Anal. Calcd. For C23H14ClF2N3O2: C, 63.09; H,
3.22; N, 9.60. Found: C, 62.91; H, 3.31; N, 9.42.
mercial fungicides thiophanate ethyl, iprodione, and jinggangmycin
as a control against mentioned above five fungi were evaluated at
the same condition. The relative inhibition rate of the circle myce-
lium compared to blank assay was calculated via the following
equation:
dex ꢀ dex 0
5-(4-chloro-2-fluorophenyl)-3-(4-nitrophenyl)-1-phenyl-1a,6a-dihydro-
Relative inhibition rate ð%Þ ¼
ꢁ 100%
dex
pyrrolo[3,4-c]pyrazole-4,6-dione (5h). dark brown crystal, 67.2%
1
yield; m. p. 259–261 ꢀC; H NMR (DMSO-d6, 400 MHz), d: 5.53 (s,
where dex is the extended diameter of the circle mycelium during
the blank assay; and d¢ex, is the extended diameter of the circle
mycelium during testing.
CHCO, 1H) 5.74 (s, NCHCO, 1H), 7.03 (s, ArH, 1H), 7.40–7.70 (m,
ArH, 8H), 8.25–8.33 (m, ArH, 4H). MS (ESI), m ⁄ z: 463 [M-H]),
499[M-H+Cl]), Anal. Calcd. For C23H15ClFN4O4: C, 59.43; H, 3.04; N,
12.05. Found: C, 59.14; H, 3.24; N, 12.25.
Crystal structure determination
5-(4-chloro-2-fluorophenyl)-1-phenyl-3-m-tolyl-1a,6a-dihydro-pyrrol-
The crystal of compound 5l with dimensions of 0.22 · 0.20 ·
0.16 mm was mounted on a Bruker SMARTb 1000 charge-couple
device (CCD) area-detector diffractometer with a graphite-monochro-
mated MoKa radiation (k = 0.71073ꢀ) by using a phi and scan
modes at 113(2) K in the range of 2.52ꢀ £ h £ 25.0ꢀ. The crystal
belongs to Monoclinic system with space group P2_1 ⁄ c and crystal
parameters of a = 40.243(8) ꢀ, b = 11.353(2) ꢀ, c = 17.635(4) ꢀ,
a = 90ꢀ, b = 90ꢀ, c = 90 ꢀ, V = 8057(3) A3, Dc = 1.498 mg ⁄ m3. The
absorption coefficient l = 0.3600 ⁄ mm, and Z = 16. The structure
was solved by direct methods with SHELXS-97c,d and refined by the
full-matrix least squares method on F2 data using SHELXL-97. The
final full-matrix least squares refinement gave R = 0.039000 and
o[3,4-c]pyrazole-4,6-dione (5i). light yellow crystal, 34.4% yield; m. p.
206–208 ꢀC; H NMR (DMSO-d6, 300 MHz), d: 3.33 (s, ArCH3, 3H),
5.43 (s, CHCO, 1H), 5.55 (s, NCHCO, 1H), 6.96(t, J = 7.2 Hz, ArH, 1H),
7.27 (t, J = 7.2 Hz, ArH, 1H), 7.33–7.40 (m, ArH, 3H), 7.51 (d,
J = 7.8 Hz, ArH,4H), 7.70 (s, ArH,1H), 7.80–7.85 (m, ArH,2H). MS (ESI),
m ⁄ z: 432 [M-H]), 464[M-H+CH3OH]). Anal. Calcd. For C24H17ClFN3O2:
C, 66.44; H, 3.95; N, 9.69. Found: C, 66.19; H, 4.18; N, 9.70.
1
5-(4-chloro-2-fluorophenyl)-3-(4-methoxyphenyl)-1-phenyl-1a,6a-dihy-
dro-pyrrolo[3,4-c]pyrazole-4,6-dione (5j). light yellow crystal, 21.7%
1
yield; m. p. 196–198 ꢀC; H NMR (DMSO-d6, 300 MHz), d: 3.82 (s,
ArOCH3, 3H), 5.41 (s, CHCO, 1H), 5.49 (s, NCHCO, 1H), 6.94(t,
J = 6.9 Hz, ArH, 1H), 7.06 (d, J = 9.0 Hz, ArH, 2H), 7.28–7.37 (m,
ArH,2H), 7.48(d, J = 8.4 Hz, ArH,4H), 7.69(s, ArH,1H),7.96 (d, J =
8.7 Hz, ArH,2H). MS (ESI), m ⁄ z: 448 [M-H]). Anal. Calcd. For C24H17
ClFN3O3: C, 64.08; H, 3.81; N, 9.34. Found: C, 64.10; H, 4.05; N, 9.41.
2
2
wR = 0.110000 (w = 1 ⁄ [r2(Fo ) + (0.0562P)2] where P = (Fo + 2
Fc2) ⁄ 3, S = 1.12, (D ⁄ r)max <0.001000, Dqmax = 1.200 e ꢀ3 and
Dqmin = )0.28 e ꢀ3.
Results and discussion
5-(4-chloro-2-fluorophenyl)-3-(2,4-dichlorophenyl)-1-phenyl-1,6a-dihy-
dropyrrolo[3,4-c]pyrazole-4,6-dione (5k). yellow crystal, 57.7% yield;
m. p. 97–99 ꢀC; 1H NMR (DMSO-d6, 300 MHz), d: 5.57 (s, CHCO,
1H), 5.64 (s, NCHCO, 1H), 6.98 (t, J = 7.2 Hz, ArH, 1H), 7.36(t,
J = 7.5 Hz, ArH, 2H), 7.44–7.49 (m, ArH, 4H), 7.63 (dd, J = 8.4 Hz,
ArH, 1H), 7.69 (d, J = 8.4 Hz, ArH,1H), 7.77(d, J = 1.8 Hz ArH,1H),
7.87 (d, J = 8.1 Hz, ArH, 1H). MS (ESI), m ⁄ z: 486 [M-H]). Anal.
Calcd. For C23H13Cl3FN3O2: C, 56.52; H, 2.68; N, 8.60. Found: C,
56.52; H, 2.77; N, 8.59.
Synthesis
Pyrazole derivatives 5a-5l were prepared according to the proce-
dures described in Scheme 1. Treatment of substituted benzoyl
phenylhydrazine with Ph3P-CCl4 in acetonitrile at room tempera-
ture gave the corresponding a-chlorohydrazones which reacted
with N-(4-chloro-2-fluoro phenyl)maleimide as dipolarophiles in
the presence of triethylamine to give the title compounds. In
our experiments, we found that electron-donating groups or
electron-withdrawing groups on the aromatic ring have little
effect on the yields of most of the compounds, while the yield
of 5e was relatively higher than others. The results indicate the
nitrilimine with alkyl substituents may be generated and under-
taken 1,3-dipolar cycloaddition more easily than that with aryl
substituents.
5-(4-chloro-2-fluorophenyl)-3-(2-chlorophenyl)-1-phenyl-1a,6a-dihydro-
pyrrolo[3,4-c]pyrazole-4,6-dione (5l). yellow crystal, 41.9% yield; m.
1
p. 153–155 ꢀC; H NMR (DMSO-d6, 300 MHz), d: 5.57 (s, CHCO, 1H),
5.63 (s, OCHCO, 1H), 6.97 (t, J = 7.2 Hz, ArH, 1H), 7.28 (s, ArH, 1H),
7.36 (t, J = 7.2 Hz, ArH, 2H), 7.45–7.49 (m, ArH, 5H), 7.58–7.61 (m,
ArH, 1H), 7.68–7.72 (m, ArH, 1H), 7.81 (s, ArH, 1H). MS (ESI), m ⁄ z:
452 [M-H]), 484[M-H+CH3OH]), Anal. Calcd. For C23H14Cl2FN3O2: C,
60.81; H, 3.11; N, 9.25. Found: C, 61.08; H, 3.02; N, 8.99.
All the title compounds were confirmed by 1H NMR, MS, and
elemental analyses. Moreover, 5-(4-chloro-2-fluorophenyl)-3-(2-
chlorophenyl)-1a,6a-dihydro-pyrrolo[3,4-c]pyrazole-4,6-dione (5l) has
been structurally characterized in detail using X-ray analysis.
Antifungal activities
Fungicidal activities of the title compounds against Corynespora
cassiicola, Pseudomonas syringae pv. Lachrymans, Ascochyta Citral-
lina Smith, Pseudoperonospora cubensis, and Sclerotinia sclerotio-
rum were evaluated according to the reference (25). The culture
plates were cultivated at (24 € 1) ꢀC. Fungicidal activities of com-
Crystal structure
The structure of compound 5l was further confirmed by single
crystal X-ray diffraction analysis (Figure 1A). From the molecular
Chem Biol Drug Des 2010; 75: 489–493
491

Zhang et al.
structure, it can be seen that pyrazoline ring and substituted ben-
zene ring are not coplanar which is different with that of
5-(4-chloro-2- fluorophenyl)-3-(3-methoxyphenyl)-3a,6a-dihydro-pyrrol-
o[3,4-d]isoxazole-4,6-dione20(Figure 1B), and the dihedral angel
between the pyrazoline ring and maleimide ring is 109.9ꢀ. The
X-ray analysis reveals that in the compounds 5l and 5-(4-chloro-2-
fluorophenyl)-3-(3-methoxyphenyl) -3a,6a-dihydro-pyrrolo [3,4-d]isox-
azole-4,6-dione, two hydrogens of the bridge head are both in the
same side of the ring, which indicates that 1,3-dipolar cycloaddition
reaction is according to carrying on the same surface addition
(syn-addition pattern) in our experiments.
A
Antifungal activities and structure–activity
relationship
The in vivo fungicidal results of the title compounds against
Corynespora cassiicola, Pseudomonas syringae pv. Lachrymans,
Ascochyta Citrallina Smith, Pseudoperonospora cubensis, and
Sclerotinia sclerotiorum were listed in Table 1. Most of the title
compounds exhibit significant fungicidal activities against Cory-
nespora cassiicola, which was comparable with that of the com-
mercial fungicides thiophanate ethyl, iprodione, jinggangmycin.
Among them, compound 5a had good fungicidal activity against
Pseudomonas syringae pv. Lachrymans, and compounds 5g and
5j displayed high fungicidal activity against Corynespora cassiico-
la. All the title compounds did not exhibit significant fungicidal
activity against Sclerotinia sclerotiorum. The data given in
Table 1 indicated that the change in substituent at phenyl ring
affects the antifungal activity against Corynespora cassiicola.
When the benzene ring is substituted by halogen, the compounds
generally have excellent antifungal activity against Corynespora
cassiicola, as 5b, 5g. While for di-halogen, alkane, or H substit-
uents, the activities decreased for 5a, 5c, and 5k. Hence, title
compound could be useful for further optimization work in finding
the potential antifungal compounds.
B
Acknowledgments
This work was supported by National Basic Research Key Program
of China (No. 2003CB114406), National Natural Science Foundation
Figure 1: The crystal structure of compound 5l.
Table 1: Antifungal activities of
title compounds (% inhibition)
Corynespora Pseudomonas
Ascochyta
Pseudopero
Sclerotinia
No.
R
cassiicola
syringae pv Lachrymans Citrullina Smith nospora cubensis sclerotiorum
5a
5b
5c
5d
H
o-F
p-CH3
m-Cl
45.85
87.86
)5.13
81.62
65.54
86.63
91.92
77.03
86.67
89.99
71.51
35.83
13.82
9.64
52.12
48.63
38.38
35.29
31.08
31.08
22.51
18.26
5.34
37.17
25.45
17.37
28.33
20.59
24.98
26.11
29.70
12.41
14.00
46.52
68.71
55.92
56.31
-64.19
25.40
-3.31
-4.42
-31.49
-10.70
2.35
31.70
31.84
19.53
5.89
5e 2,4-Cl2PhOCH2
5f
24.56
50.52
27.53
60.06
54.79
10.46
30.73
54.15
38.49
-11.42
p-Cl
p-F
p-NO2
m-CH3
p- OCH3
5g
5h
5i
5j
5k
4.88
2.4-Cl2 64.90
20.39
100.00
98.35
48.82
Thiophanate-methyl
Iprodione
Jinggangmycin
78.75
53.52
78.20
83.39
97.84
26.89
492
Chem Biol Drug Des 2010; 75: 489–493

Antifungal Activities of New Pyrazole Derivatives
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