Synthesis and insecticidal activity of 5-substituted-sulfonylaminopyrazole derivatives

Article abstract of DOI:10.3184/030823410X12656400473100

The reaction of 5-amino-3-cyano-1-(2, 6-dichloro-4-trifluoromethylphenyl)- 1H-pyrazole and 5-amino-1-[2, 6-dichloro-4-(trifluoromethylphenyl]-4- trifluoromethylsulfinyl-1H-pyrazole-3-carbonitrile (Fipronil) with arylsulfonyl chlorides gave the 5-arylsulfo

Full text of DOI:10.3184/030823410X12656400473100

92 RESEARCH PAPER
FEBRUARY, 92–94
JOURNAL OF CHEMICAL RESEARCH 2010
Synthesis and insecticidal activity of 5-substituted-sulfonylaminopyrazole
derivatives
Xiaohong Zhangb, Ting Lvb, Shuyan Lib, Yena Chenb and ping Zhonga,b*
aOujiang College, Wenzhou Universtity, Wenzhou 325035, P.R. China
bCollege of Chemistry and Material Engineering, Wenzhou Universtity, Wenzhou 325035, P.R. China
The reaction of 5-amino-3-cyano-1-(2, 6-dichloro-4-trifluoromethylphenyl) -1H-pyrazole and 5-amino-1-[2, 6-dichloro-
4-(trifluoromethylphenyl]-4-trifluoromethylsulfinyl-1H-pyrazole-3-carbonitrile (Fipronil) with arylsulfonyl chlorides
gave the 5-arylsulfonamides at room temperature in high yields. Some of these compounds had insecticidal activity
against pests such as army worm and rice plant hopper.
Keywords: pyrazole, Fipronil, sulfonyl chloride, sulfonylaminopyrazole
Phenylpyrazole derivatives have attracted attention owing to
their biological activities,1–5 as potential inhibitors of HIV,6
herbicides,7 analgesic drugs,8 and antiviral bioassay.9 Pyrazole
derivatives possessing fluorine-containing groups, for exam-
ple, fipronil (2) [5-amino-1-[2, 6-dichloro-4-(trifluoromethyl)-
phenyl]-4-trifluoromethylsulfinyl-lH-pyrazole-3-carbonitrile]
are effective against a host of insect pests of crops including
grass hoppers, boll weevils, rice insects, termites, houseflies,
fruitflies and thrips.10–12 Similar insecticidal or antimicrobial
activity is observed for some sulfonylaminopyrazoles.13,14
Consequently we thought that a 5-substituted-sulfonylamino-
pyrazole of fipronil (2) or its intermediate 5-amino-3-cyano-1-
(2, 6-dichloro-4-trifluoromethylphenyl)-1H-pyrazole(1)might
have the same high insecticidal activity. Here we describe
an effcient synthesis of 5-substituted-sulfonylaminopyrazole
based on the reaction of 5-amino-3-cyano-1-(2, 6-dichloro-4-
trifluoromethylphenyl)-1H-pyrazole (1) and 5-amino-1-[2, 6-
dichloro-4-(trifluoromethylphenyl]-4-trifluoromethylsulfinyl-
1H-pyrazole-3-carbonitrile (Fipronil, 2) with different substi-
tuted sulfonyl chlorides at room temperature. Some of these
compounds had insecticidal activity against pests such as army
worm and rice plant hopper.
Results and discussion
The starting materials, 5-amino-3-cyano-1-(2, 6-dichloro-4-
trifluoromethylphenyl) -1H-pyrazole (1) and 5-amino-1-[2, 6-
dichloro-4-(trifluoromethylphenyl]-4-trifluoromethylsulfinyl-
1H-pyrazole-3-carbonitrile (Fipronil 2) were prepared by the
reported procedures.15,16
The experimental procedures were simple. Treatment of 1
with different substituted sulfonyl chloride using pyridine as
the acid-binding agent gave the aimed compounds 1a–e in
good yields (Scheme 1). In the light of the steric hindrance of
the group CF3SO to the NH in the substrate 2, we used NaH to
increase the reactivity, and 22a–f were formed quickly in good
yields (Scheme 2 and Table 1).
It was very interesting to find that a 5-dimethylsulfonyl-
amide was obtained when the substituted sulfonyl chloride
was methylsulfonyl chloride, even if the mol ratio of 1 and
methylsulfonyl chloride was 1:1. It is possible that that the
Scheme 1
* Correspondent. E-mail: zhongp0512@163.com

JOURNAL OF CHEMICAL RESEARCH 2010 93
Scheme 2
CD3COCD3 as a solvent with tetramethylsilane (TMS) as the internal
standard. J values are given in Hz. Compounds were characterised
by elemental analyses using a Carlo-Erba EA–1112 instrument. IR
spectra were measured on a Bruker VECTOR55 instrument. Silica gel
60 GF254 was used for analytical and preparative TLC.
Table 1 The yields of compounds 1a–e and 2a–f
Entry
R=
Yield/%
1a
1b
1c
1d
1e
2a
2b
2c
2d
2e
2f
C6H5
86.5
85.2
84.5
80
4-CH C6H
4-CH33OC64H4
4-BrC6H4
CH3
General procedure for preparation of 5-substituted-sulfonylamino-
pyrazole (1a–e)
88.7
95
4-BrC H
5-Amino-3-cyano-1-(2, 6-dichloro-4-trifluoromethylphenyl)pyrazole
(1, about 5 mmol) was stirred with the substituted sulfonylchloride
(5 mmol) in pyridine (5 mL) overnight at room temperature. The
residue was then poured into cold water and filtered to afford solid
products, which were chromatographed on silica gel, eluting with
petroleum ether and ethyl acetate (5:1). The solvent was removed
under reduced pressure to give the title compounds 1a–e respectively.
1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-phenylsulfonyl-
amino)-1H-pyrazole-3-carbonitrile (1a): White solid, yield (86.5%);
m.p. 173–175 °C; IR (KBr) νmax 3245 (NH), 2249 (C≡N), 1560 (pyr-
azolyl), 1510 (phenyl), 1380, 891, 816 cm−1; 1H NMR (CDCl3,
300 MHz) δ 9.87 (s, 1H), 8.04 (s. 2H), 7.87 (m, 2H), 7.72 (m, 1H),
7.63 (m, 2H), 6.89 (s, 1H); 13C NMR (CDCl3, 75 MHz) δ: 139.4,
138.7, 136.2, 134.2 (q, J = 34 Hz), 132.8, 130.4, 128.4, 127.3, 126.1,
124.1 (q, J = 271 Hz), 112.8, 103.9, 101.3;. MS m/z (%): 460(M+);
Anal. Calcd for C17H9Cl2F3N4O2S: C, 44.27; H, 1.97. Found: C, 44.06;
H, 1.91%.
2-NO26C 4H4
5-Brom6othiophene
4-CH C6H
4-CH33OC64H4
C6H5
96
93
88
80
90
steric hindrance of the first methylsulfonyl group is small,
and that the remaining H of the NH can be easily replaced.
The IR spectra of 1a–d revealed, in each case, four charac-
teristic absorptions near 3200, 2245, 1560 and 1510 cm−1 due
to sulfonylamino-NH, nitrile (CN), pyrazolyl and phenyl
groups. The 1H NMR spectrum of 1c for example, displayed a
singlet at δ 3.91 due to the methyl protons (three protons), a
singlet signal at δ 9.72 due to pyrazolyl proton (one proton), a
singlet signal at δ 8.04 due to phenyl protons (two protons)
bearing CF3, a double signal at δ 7.12 due to phenyl protons
(four protons) carrying the bromine and a singlet signal at
δ 6.85 corresponding to the NH proton (one proton). Moreover
its mass spectrum showed at m/z = 490, which was in accord
with the calculated molecular weight C18H11Cl2F3N4O3S.
However, in the IR spectra and 1H NMR of 1e, absorptions
near 3200 cm−1 and the singlet signal at about δ 6.80 corre-
sponding to the NH proton had disappeared owing to the
absence of NH. There was a singlet signal at δ 3.54 due to
methyl protons (six protons) showing that two H atoms of NH2
were replaced by the methylsulfonyl groups.
1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-(4-methylphenyl-
sulfonylamino)-1H-pyrazole-3-carbonitrile (1b): White solid, yield
(85.2%); m.p. 237–239 °C; IR (KBr) ν 3222 (NH), 2246 (C≡N), 1563
(pyrazolyl), 1509 (phenyl), 1381, 1309, 889, 817, 666 cm−1; 1H NMR
(CDCl3, 300 MHz) δ 9.90 (s, 1H), 8.02 (s, 2H), 7.77 (d, J = 8.4 Hz,
2H), 7.42 (d, J = 8.4 Hz, 2H), 6.85 (s, 1H), 2.43 (s, 3H); 13C NMR
(CDCl3, 75 MHz) δ 145.8, 140.6, 137.2, 134.8 (q, J = 34 Hz), 130.7,
130.4, 128.7, 128.6, 128.2, 123.2 (q, J = 271 Hz), 117.8, 113.8, 103.6,
21.5; MS m/z (%): 474 (M+), 476 (M+ + 2). Anal. Calcd for
C18H11Cl2F3N4O2S: C, 45.49; H, 2.33. Found: C, 45.36; H, 2.25%.
1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-(4-methoxyphenyl-
sulfonylamino)-1H-pyrazole-3-carbonitrile (1c): White solid, yield
(84.5%); m.p. 219–220 °C; IR (KBr) ν 3215 (NH), 2247 (C≡N), 1592
1
(pyrazolyl), 1500 (phenyl), 1380, 1311, 1266, 1166, 1093 cm−1; H
All elemental and spectroscopic data of compounds 2a–f
were in accord with the suggested structures.
NMR (CDCl3, 300 MHz) δ 9.72 (s, 1H), 8.04 (s, 2H), 7.12 (d, 4H),
6.85 (s, 1H), 3.91 (s, 3H); 13C NMR (CDCl3, 75 MHz) δ 144.8, 140.0,
137.1, 134.6 (q, J = 34 Hz), 131.2, 130.5, 128.7, 128.2, 127.1, 123.1
(q, J = 271 Hz), 117.9, 113.8, 103.2, 56.3. MS m/z (%): 490 (M+), 492
(M+ + 2).Anal. Calcd for C18H11Cl2F3N4O3S: C, 44.01; H, 2.26. Found:
C, 43.95; H, 2.20%.
Experimental
1
All the melting points were uncorrected. H, 13C, 19F NMR spectra
were recorded on a FT-Bruker AT-300 instrument using CDCl3 or

94 JOURNAL OF CHEMICAL RESEARCH 2010
1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-(4-bromobenzene-
sulfonylamide)-1H-pyrazole-3-carbonitrile (1d): White solid, yield
(80%); m.p. 241–243 °C; IR (KBr) ν 3235 (NH), 2248 (C≡N), 1565
1.34 (s, 3H); 13C NMR (CDCl , 75 MHz) δ 161.7, 149.5, 137.0,
136.1, 135.8, 132.8 (q, J = 33.63Hz), 127.9, 125.7, 125.6, 125.5 (q,
J = 338.7 Hz), 125.4, 120.6 (q, J = 270.8 Hz), 113.3, 111.8, 21.3;
LRMS (EI, 70 eV) m/z (%): 592 (M+ + 2), 590 (M+); Anal. Calcd for
C19H10Cl F6N4O3S2: C, 38.59; H, 1.70. Found: C, 38.51; H, 1.65%.
1-[2,62-Dichloro-4-(trifluoromethyl)phenyl]-5-(4-methoxybenzene-
sulfonylamide)-3-cyano-4-trifluoromethylthiopyrazole (2e): Yellow
solid, yield (80%); m.p. 155–158 °C; IR (KBr) ν 3232 (NH), 2247
1
(pyrazolyl), 1511 (phenyl), 1382, 1311 cm−1; H NMR (CD3COCD3,
300 MHz): 9.95 (s, 1H), 8.06 (s, 2H), 7.77–7.85 (m, 4H), 6.93 (s, 1H);
13C NMR (CD3COCD3, 75MHz): δ 140.1, 139.1, 137.1, 135.0 (q,
J = 33.8 Hz), 133.6, 130.1, 129.2, 128.4, 127.3, 127.2, 123.3 (q,
J = 271.6 Hz), 113.8, 104.2. MS m/z (%): 538 (M+), 440 (M+ + 2).
Anal. Calcd for C17H8Cl2F3N4O2BrS: C, 37.80; H, 1.49. Found: C,
37.50, H, 1.40%.
1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-dimethylsulfonylamide-
1H-pyrazole-3-carbonitrile (1e): White solid, yield (88.7%), m.p.
234–236 °C; IR (KBr) ν: 3146, 3074, 2932, 2251 (C≡N), 1570 (pyr-
azolyl), 1537 (phenyl), 1378, 1365, 1319, 1171, 1136 cm−1; 1H NMR
(CDCl , 300 MHz) δ 8.12 (s, 2H), 7.70 (s, 1H), 3.54 (s, 6H); 13C NMR
(CDCl3, 75 MHz) δ 137.1, 136.6, 135.5 (q, J = 34 Hz, ), 127.9, 127.5,
127.4, 3123.2 (q, J = 272 Hz); 114.6, 113.2, 42.8; MS m/z (%): 476
(M+); Anal. Calcd for C13H9Cl2F3N4O4S2: C 32.72, H 1.90. Found:
C 32.54, H 1.85%.
1
(C≡N), 1563 (pyrazolyl), 1510 (phenyl), 1380, 1311 cm−1; H NMR
(CDCl3, 300 MHz) δ 7.95 (s, 2H), 7.17–7.57 (m, 4H), 3.59 (s, 1H) ,
2.53 (s, 3H); 13C NMR (CDCl3, 75 MHz) δ 150.6, 142.3, 140.7, 136.0,
135.9, 132.7 (q, J = 33.8 Hz), 128.4, 126.0. 125.8, 125.5 (q,
J = 338.6 Hz), 125.4, 120.4 (q, J = 270.6 Hz), 120.0, 112.8, 52.1;
LRMS (EI, 70 eV) m/z (%): 608 (M+ + 2), 606 (M+); Anal. Calcd for
C19H10Cl2F6N4O4S , C, 37.58; H, 1.66. Found: C, 37.55; H, 1.63%.
1-[2,6-Dichlor2o-4-(trifluoromethyl)phenyl]-5-benzenesulfonyl-
amide-3-cyano-4-trifluoromethylthiopyrazole (2f): White solid, yield
(90%); m.p. 183–184°C; IR (KBr) ν 3231 (NH), 2248 (C≡N), 1564
1
(pyrazolyl), 1511 (phenyl), 1380, 1311 cm−1; H NMR (CD3SOCD3,
300 MHz) δ 8.15 (s, 2H), 7.40–7.55 (m, 5H), 3.98 (s, 1H); 13C NMR
(CD3SOCD3, 125 MHz) δ 151.3, 144.7, 136.6, 135.1, 131.8 (q,
J = 33.8 Hz), 129.9, 127.8, 125.5, 125.3 (q, J = 338.8 Hz), 124.9,
124.1, 121.7 (q, J = 270.5 Hz), 111.9, 99.3. LRMS (EI, 70 eV) m/z
(%): 578 (M+ + 2), 576 (M+); Anal. Calcd for C18H8Cl2F6N4O3S2: C,
37.45; H, 1.40. Found: C, 37.40, H, 1.35%.
General procedure for preparation of 5-substituted-sulfonylamino-
pyrazole (2a–f)
A solution of fipronil (2, 1.0 mmol) in ethyl acetate (10 mL), was
treated with sodium hydride (60%, 1.2 mmol). After stirring for 0.5 h
at 0 °C, the substituted sulfonyl chloride (1.2 mmol) was added drop-
wise. The mixture was stirred for an additional 1 h at room tempera-
ture. Aqueous ammonium chloride was added and extractive workup
with aqueous sodium carbonate and dichloromethane gave a solid
which was washed with heptane-ethyl acetate (1:1), filtered and dried
to give the title product (2a–f) .
This work was supported by the National Natural Science
Foundation of China (grant no. 20972114) and the Natural
Science Foundation of Zhejiang Province (grant no. Y407079
and Y4080027).
1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-(4-bromobenzene-
sulfonylamide)-3-cyano-4-trifluoromethylthiopyrazole (2a): Yellow
solid, yield (95%); m.p. 192–193 °C; IR (KBr) ν 3230 (NH), 2247
Received 20 November 2009; accepted 18 January 2010
Paper 090880 doi: 10.3184/030823410X12656400473100
Published online: 3 March 2010
1
(C≡N), 1564 (pyrazolyl), 1510 (phenyl), 1380, 1311 cm−1; H NMR
(CDCl3, 300 MHz) δ 7.97 (s, 2H), 7.52–7.60 (m, 4H), 3.33 (s, 1H);
13C NMR (CDCl3, 75 MHz) δ: 151.1, 145.3, 137.4, 136.0, 132.7 (q,
J = 33.9 Hz), 131.0, 128.26, 127.68, 125.5, 125.4 (q, J = 338.5 Hz),
125.2, 123.8, 120.4 (q, J = 270.7 Hz), 112.0. MS m/z (%): 654 (M+),
656 (M+ + 2); Anal. Calcd for C18H7BrCl2F6N4O3S2: C, 32.95; H, 1.08.
Found: C, 32.90; H, 1.05%.
References
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1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-(2-nitrobenzene-
sulfonylamide)-3-cyano-4-trifluoromethylthiopyrazole (2b): Yellow
solid, yield (96%); m.p. 167–169 °C; IR (KBr) ν 3233 (NH), 2245
1
(C≡N), 1565 (pyrazolyl), 1511 (phenyl), 1380, 1311 cm−1; H NMR
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(CDCl3, 300 MHz) δ 7.96 (s, 2H), 7.56–7.66 (m, 4H), 3.13 (s, 1H); 13
C
NMR (CDCl3, 75 MHz) δ 151.68, 147.8, 137.9, 137.4, 135.9, 132.7
(q, J = 34 Hz), 131.2, 130.7, 128.2, 125.5, 125.0 (q, J = 338.6 Hz),
124.1, 123.7, 123.1, 120.5 (q, J = 270.8 Hz), 112.1; LRMS (EI,
70 eV) m/z (%): 623 (M+ + 2), 621 (M+); Anal. Calcd for
C18H7Cl2F6N O5S2: C, 34.74; H, 1.13. Found: C, 34.70; H, 1.10%.
1-[2,6-Dic5hloro-4-(trifluoromethyl)phenyl]-5-[3-(5-bromothiophene)
sulfonylamide]-3-cyano-4-trifluoromethylthiopyrazole (2c): yellow
solid, yield (93%); m.p. 175–176 °C; IR (KBr) ν 3230 (NH), 2247
6
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1
(C≡N), 1565 (pyrazolyl), 1510 (phenyl), 1378, 1311 cm−1; H NMR
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(CDCl3, 300 MHz) δ 7.97 (s, 2H), 7.00–7.04 (m, 2H), 3.03 (s, 1H); 13
C
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NMR (CDCl3, 75 MHz) δ 150.0, 136.3, 136.0, 132.0 (q, J = 33.7 Hz),
129.3, 127.9, 125.5, 125.4, 125.3 (q, J = 338.6 Hz), 125.2, 120.8 (q,
J = 270.4 Hz), 114.4, 112.1, 99.5; LRMS (EI, 70 eV) m/z (%): 662
(M+ + 2), 660 (M+);Anal. Calcd for C16H5BrCl2F6N4O3S3: C, 29.02; H,
0.76. Found: C, 29.00; H, 0.75%.
1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-(4-methylbenzene-
sulfonylamide)-3-cyano-4-trifluoromethylthiopyrazole (2d): Yellow
solid, yield (88%); m.p. 125–127 °C; IR (KBr) ν 3231 (NH), 2248
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1
(C≡N), 1564 (pyrazolyl), 1512 (phenyl), 1380, 1311 cm−1; H NMR
(CDCl3, 300 MHz) δ 7.96 (s, 2H), 6.90–7.60 (m, 4H), 3.51 (s, 1H),

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