Pd-catalyzed direct arylation of phenylpyrazole: Synthesis of fipronil derivatives with aryl boronic acids promoted by a stoichiometric amount of NIS

Article abstract of DOI:10.1016/j.jfluchem.2012.02.007

The palladium-catalyzed direct arylation of phenylpyrazole with aryl boronic acid promoted by a stoichiometric amount of NIS has been reported. Several phenyl pyrazoles, especially for those with trifluoromethyl groups, can participate in the reaction, providing a series of fipronil derivatives of 4-aryl-phenylpyrazole with potential bioactivity in moderate to good yields. All the compounds were characterized by ¹H NMR, ¹³C NMR and HRMS spectroscopic techniques.

Full text of DOI:10.1016/j.jfluchem.2012.02.007

Journal of Fluorine Chemistry 137 (2012) 44–49
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Pd-catalyzed direct arylation of phenylpyrazole: Synthesis of fipronil derivatives
with aryl boronic acids promoted by a stoichiometric amount of NIS
a
Ting Lv a, Xiao-Hong Zhang a, , Jiang-Sheng Han , Ping Zhong
*
a,b,**
a College of Chemistry and Materials Science, Wenzhou University, Wenzhou 325035, China
b Oujiang College, Wenzhou University, Wenzhou 325035, China
A R T I C L E I N F O
A B S T R A C T
Article history:
The palladium-catalyzed direct arylation of phenylpyrazole with aryl boronic acid promoted by a
stoichiometric amount of NIS has been reported. Several phenyl pyrazoles, especially for those with
trifluoromethyl groups, can participate in the reaction, providing a series of fipronil derivatives of 4-aryl-
phenylpyrazole with potential bioactivity in moderate to good yields. All the compounds were
characterized by 1H NMR, 13C NMR and HRMS spectroscopic techniques.
Received 21 December 2011
Received in revised form 7 February 2012
Accepted 9 February 2012
Available online 21 February 2012
ß 2012 Elsevier B.V. All rights reserved.
Keywords:
Palladium-catalyzed
Direct arylation
Phenylpyrazole
Fipronil derivatives
Trifluoromethyl group
1. Introduction
synthesis of 4-aryl-1-phenylpyrazoles containing CF3 group is
still a great challenge.
Phenyl pyrazole is an important class of heterocyclic com-
pounds and has shown a wide range of biological activities [1]. In
addition, phenyl pyrazole derivatives possessing fluorine-con-
taining groups, for example, fipronil (I, Fig. 1) [5-amino-1-[2,6-
dichloro-4-(trifluoromethyl)-phenyl]-4-trifluoromethylsulfinyl-
lH-pyrazole-3-carbonitrile] and ethiprole (II, Fig. 1), with 4-EtSO
replacing with the 4-CF3SO, are effective against a host of insect
pests of crops including grass hoppers, boll weevils, rice insects,
termites, houseflies, fruitflies and thrips [2]. The new analog of
desulfinylethiprole (III, Fig. 1) was surprisingly found to have high
insecticidal activity [3]. So we believe that 4-aryl-1-phenylpyr-
azole compounds (IV, Fig. 1) may have the same high insecticidal
activity. However, there are relatively few reports for the
synthesis of compounds IV [4], which was synthesized mainly
via the reaction of 4-iodo-1-phenylpyrazole with arylboronic acid
[5]. This method requires to prepare substrates to form the
electrophiles, and the overall process is neither atom-economical
nor green. Therefore, the protocol for novel procedures for the
Recently, great interests have been aroused to develop mild
methods for the direct functionalization of C–H to construct C–C
[6], C–N [7], C–O [8] and C–S [9] bonds. It is well known that
Suzuki–Miyaura reaction is one of the most attractive methods to
construct C–C bond [10]. With the development of the Suzuki–
Miyaura reaction, boronic acids have been developed as powerful
reagents owing to their nontoxicity, stability and compatibility
with most functional groups [11]. So we envisioned that 4-aryl-1-
phenylpyrazoles can be obtained through the metal-catalyzed
direct arylation of phenylpyrazoles with aryl boronic acids. And it
is very fortunate that the direct arylation of phenylpyrazole
occurred smoothly using PdCl2(PPh3)2 as catalyst. Here, we
describe the novel synthesis of 4-aryl-1-phenylpyrazole deriva-
tives containing CF3 group. All the compounds were characterized
by 1H NMR, 13C NMR and HRMS spectroscopic techniques.
2. Results and discussion
We choose the reaction of 5-amino-1-[2,6-dichloro-4-trifluor-
omethylphenyl]-l-H-pyrazole-3-carbonitrile (1a) with phenyl
boronic acid (2a) as a model system to determine the optimal
reaction conditions (Table 1). Initially, a series of Pd catalysts,
including PdCl2, Pd(OAc)2, Pd(PPh3)4 and PdCl2(PPh3)2, were tested
for the reaction using 2 equiv NaHCO3 as base, 1 equiv NIS as iodine
source, C2H5OH:H2O (3:1) as solvent at 80 8C under N2 (entries 1–
4). Among these catalysts screened, PdCl2(PPh3)2 showed the
* Corresponding author. Tel.: +86 0577 86689338; fax: +86 0577 86689338.
** Corresponding author at: College of Chemistry and Materials Science, Wenzhou
University, Wenzhou 325035, China. Tel.: +86 0577 86689338;
fax: +86 0577 86689338.
E-mail addresses: kamenzxh@163.com (X.-H. Zhang), zhongp0512@163.com
(P. Zhong).
0022-1139/$ – see front matter ß 2012 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2012.02.007

T. Lv et al. / Journal of Fluorine Chemistry 137 (2012) 44–49
45
but only 75% yield of 3 was obtained when decreasing the amount
of NIS to 0.9 equiv (entries 14–15). It was interesting that no
arylated product but only the by-product 4-iodo-1-phenylpyrazole
can be obtained in high yields (entries 16–17) when the mixture
solvent of C2H5OH:H2O was replaced with C2H5OH and dioxane.
With the optimal catalytic system in hand, the scope of boronic
acids in the reaction with 1a was next investigated (Table 2).
Gratifyingly, aryl boronic acids with electron-rich and electron-
poor groups were successfully converted to the corresponding
arylated products in moderate to good yields. Generally speaking,
the electron-donating groups, such as methoxy, methyl and ethyl,
on the phenyl ring of boronic acids were beneficial for the
transformation (entries 2–4), whereas electron-withdrawing
groups like chloro, fluoro and trifluoromethyl, decreased the
efficiency (entries 7–9). Yet, steric hindrance affected the
efficiency. For example, 88% yield of compound 4 without ortho
substituent was isolated, while the yield of compounds 7 and 8
derived from ortho-substituted boronic acid were decreased to
69% and 60%, respectively (entries 5–6).
Subsequently, the substrate scope was extended to 5-amino-1-
[2-chloro-4-trifluoromethylphenyl]-l-H-pyrazole-3-carbonitrile
(1b) and 5-amino-1-phenyl-3-methylpyrazole (1c). With the
strong electron-withdrawing group of trifluoromethyl on the
phenyl ring, substrate 1a and 1b reacted with aryl boronic acids
smoothly to give the arylated products in good yields (entries 1–
10). However, when CF3 on the phenyl ring of substrate 1c
disappeared, as well as CH3 instead of CN on the pyrazole ring, no
more than 62% of arylated products can be obtained (entries 11–
18). The relatively poor reactivity may largely attribute to absence
Fig. 1. Fipronil (I) and analogs (II, III, IV).
highest efficiency. However, when the reaction was conducted
under atmospheric condition, the yield was decreased to 54%
(entry 3). Other transition-metal catalyst, Cu(OAc)2 was also
measured and the byproduct of 4-iodo-1-phenylpyrazole was
found to be obtained in a high yield (entry 5). Next, NaHCO3 was
replaced with different bases, such as CH3ONa, Cs2CO3, K2CO3, t-
BuOK, Na2CO3 and CH3COOK, the results indicated that the identity
of base was critical to the success of the direct arylation (entries 6–
11). Subsequently, when the amount of NaHCO3 was decreased to
1.5 equiv, the yield of 3 was reduced to 50% (entry 3). Promoted by
the help from NIS, other iodide reagents, such as I2 or ICl, were
investigated in the presence of PdCl2(PPh3)2 and they are less
effective than NIS (entries 12–13). Based on our previous work
[12], we think NIS promoted the generation of 4-iodo-1-
phenylpyrazole in situ compared to I2 and ICl, which was then
reacted with phenyl boronic acid to give the arylated product 3. It
is noteworthy the slightly excess of NIS affected the yield slightly,
Table 1
Optimization of the arylation conditions.a
Entry
Catalyst
Base
Iodide source
Solvent
Yield (%)b
1
PdCl2
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
CH3ONa
Cs2CO3
NIS
NIS
NIS
NIS
NIS
NIS
NIS
NIS
NIS
NIS
NIS
I2
C2H5OH:H2O
C2H5OH:H2O
C2H5OH:H2O
C2H5OH:H2O
C2H5OH:H2O
C2H5OH:H2O
C2H5OH:H2O
C2H5OH:H2O
C2H5OH:H2O
C2H5OH:H2O
C2H5OH:H2O
C2H5OH:H2O
C2H5OH:H2O
C2H5OH:H2O
C2H5OH:H2O
C2H5OH
25
2
Pd(OAc)2
8
3
PdCl2(PPh3)2
Pd(PPh3)4
85 (50c, 54d)
4
52
90d
36
6
5
Cu(OAc)2
6
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
7
8
K2CO3
32
30
20
19
36
40
86
75
96g
93g
9
t-BuOK
Na2CO3
CH3COOK
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
10
11
12
13
14e
15f
16
17
ICl
NIS
NIS
NIS
NIS
Dioxane
a
Reaction conditions: 1a (0.2 mmol), 2a (0.4 mmol), [NIS, I2 or ICl] (1 equiv), [Pd] or [Cu] (10 mol%), base (0.4 mmol), C2H5OH:H2O (3:1), N2, 80 8C for 18 h.
b
c
d
e
f
Isolated yield.
NaHCO3 (0.3 mmol).
Without N2.
NIS (1.1 equiv).
NIS (0.9 equiv).
g
The yield of by-product 4-iodo-1-phenylpyrazole

46
T. Lv et al. / Journal of Fluorine Chemistry 137 (2012) 44–49
Table 2
Pd-catalyzed arylation of phenylpyrazole with arylboronic acid.a
b
Entry
1
Pyrazole
R2
H
R3
H
Product (yield %)
3 (85)
1a
2
3
4
5
6
7
8
9
1a
1a
1a
1a
1a
1a
1a
1a
OCH3
CH3
CH2CH3
H
H
4 (88)
5 (87)
6 (86)
7 (69)
8 (60)
9 (75)
10 (71)
11 (68)
H
H
OCH3
OCH3
H
Cl
Cl
F
H
CF3
H
10
H
H
12 (83)
1b
11
H
H
13 (55)
1c
12
13
14
15
16
17
18
1c
1c
1c
1c
1c
1c
1c
OCH3
H
14 (62)
15 (60)
16 (61)
17 (43)
18 (41)
19 (50)
20 (52)
CH3
H
CH2CH3
H
H
H
F
CH3
Cl
H
Cl
H
a
Reaction conditions: 1a (0.2 mmol), 2a (0.4 mmol), [NIS] (0.2 mmol), [Pd] (10 mol%), NaHCO3 (0.4 mmol), C2H5OH:H2O (3:1), N2, 80 8C for 18 h.
Isolated yield.
b
of CN, which displayed the existence of electron-withdrawing
3. Conclusion
substituents on the pyrazole ring benefited the direct arylation of
phenylpyrazole. Similarly, the substituent on the phenyl of boronic
acids affected the reaction obviously. The electron-donating
groups, such as methoxy, methyl and ethyl, on the phenyl ring
of boronic acids favored the reaction (entries 12–14) and gave
higher yields of products than the electron-withdrawing groups
(entries 17–18). Meanwhile, steric hindrance affected the efficien-
cy to give compounds 17 and 18 in lower yields of 43% and 41%,
respectively (entries 15–16).
In summary, we have presented a novel method for palladium-
catalyzed direct arylation of phenylpyrazole with the aid of a
stoichiometric amount of NIS. Adopting the method, various
substrates can tolerate the conditions and a series of fipronil
derivatives of 4-aryl-phenylpyrazole with potential bioactivity
were synthesized in moderate to good yields. Undoubtedly, this
efficient method will be useful for the synthesis of trifluoromethyl-
containing 4-aryl-phenylpyrazole derivatives for drug discovery.

T. Lv et al. / Journal of Fluorine Chemistry 137 (2012) 44–49
47
4. Experimental
13C NMR (500 MHz, DMSO): 146.2, 142.6, 135.8, 132.7
(J = 33.75 Hz), 128.4, 127.2, 126.9, 126.5, 126.4, 124.6, 123.4
(J = 271.25 Hz), 114.5, 104.9, 27.9, 15.5.
Chemicals were either purchased or purified by standard
techniques. NMR spectroscopy was performed on
HRMS (EI): calcd. for C19H14Cl2F3N4 (M+): 425.0542; found:
425.0533.
a Bruker
Avance-300 spectrometer operating at 500 MHz (1H NMR) and
125 MHz (13C NMR), using DMSO as the solvent with tetramethyl-
silane (TMS) as an internal standard at room temperature. The
coupling constants J are given in Hz. The high resolution mass
spectrometer was Bruker micrOTOF-QII (ESI). All reactions are
happened under N2 atmosphere. Column chromatography was
performed using EM Silica gel 60 (300–400 mesh).
5-Amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4-(2-
methoxyphenyl)-1H-pyrazole-3-carbonitrile (7)
Light yellow solid; mp 206–208 8C.
1H NMR (500 MHz, DMSO): 8.29 (s, 2H), 7.42–7.09 (m, 4H), 5.94
(s, 2H), 3.88 (s, 3H).
13C NMR (500 MHz, DMSO): 156.3, 146.8, 136.1, 135.9, 132.6
(J = 33.75 Hz), 130.2, 129.0, 126.5, 126.3, 122.4 (J = 275 Hz),
120.6, 118.2, 114.4, 111.7, 101.7, 55.3.
4.1. Typical experimental procedure for the Pd-catalyzed direct
arylation of phenylpyrazole with arylboronic acid
HRMS (EI): calcd. for C18H12Cl2F3N4O (M+): 427.0335; found:
427.0318.
Phenylpyrazole (0.2 mmol), arylboronic acid (0.4 mmol), NIS
(0.2 mmol), [Pd] (10 mol%), NaHCO3 (0.4 mmol) and C2H5OH:H2O
(3:1, 10 mL), were added to a Schlenk tube. Then the tube was
charged with N2 and the reaction mixture was stirred at 80 8C for
18 h. After the completion of the reaction, as monitored by TLC, the
mixture was cooled and filtrated. The filtrate was extracted with
ethyl acetate and washed with brine. Then the combined organic
extracts were dried over Na2SO4, concentrated under vacuum and
the resulting residue was purified by silica gel column chroma-
tography to afford the desired products.
5-Amino-4-(5-chloro-2-methoxyphenyl)-1-(2,6-dichloro-4-
(trifluoromethyl)phenyl)-1H-pyrazole-3-carbonitrile (8)
Light yellow solid; mp 209–211 8C.
1H NMR (500 MHz, DMSO): 8.29 (s, 2H), 7.51–7.15 (m, 3H), 6.12
(s, 2H), 3.89 (s, 3H).
13C NMR (500 MHz, DMSO): 155.2, 146.9, 136.0, 135.9, 132.7
(J = 33.75 Hz), 129.5, 128.5, 126.5, 126.3, 124.2, 122.4
(J = 272.5 Hz), 120.1, 114.1, 113.3, 100.0, 55.7.
HRMS (EI): calcd. for C18H11Cl3F3N4O (M+): 460.9945; found:
460.9933.
5-Amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4-phe-
nyl-1H-pyrazole-3-carbonitrile (3)
Light yellow solid; mp 204–206 8C.
1H NMR (500 MHz, DMSO): 8.30 (s, 2H), 7.59–7.55 (m, 5H), 6.29
(s, 2H).
5-Amino-4-(4-chlorophenyl)-1-(2,6-dichloro-4-(trifluoro-
methyl)phenyl)-1H-pyrazole-3-carbonitrile (9)
13C NMR (500 MHz, DMSO): 146.3, 135.9, 132.8 (J = 33.75 Hz),
129.7, 129.0, 127.2, 126.9, 126.6, 126.5, 124.7, 122.3
(J = 271.25 Hz), 114.5, 104.8.
Light yellow solid; mp 208–210 8C.
HRMS (EI): calcd. for C17H10Cl2F3N4 (M+): 397.0229; found:
397.0206.
1H NMR (500 MHz, DMSO): 8.32 (s, 2H), 7.61–7.60 (m, 4H), 6.38
(s, 2H).
13C NMR (500 MHz, DMSO): 146.5, 135.9, 135.8, 132.8
(J = 32.5 Hz), 131.4, 129.0, 128.6, 128.4, 126.6, 124.6, 122.3
(J = 257 Hz), 114.2, 103.6.
5-Amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4-(4-
methoxyphenyl)-1H-pyrazole-3-carbonitrile (4)
HRMS (EI): calcd. for C17H8Cl3F3N4 (M+): 430.9826; found:
430.9830.
Light yellow solid; mp 206–208 8C.
1H NMR (500 MHz, DMSO): 8.28 (s, 2H), 7.49 (d, J = 10 Hz, 2H),
7.11 (d, J = 10 Hz, 2H), 6.10 (s, 2H), 3.85 (s, 3H).
13C NMR (500 MHz, DMSO): 158.3, 146.0, 136.0, 135.9, 132.7
(J = 33.75 Hz), 128.7, 126.5, 126.4, 124.6, 122.4 (J = 271.25 Hz),
121.9, 114.6, 104.9, 55.2.
5-Amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4-(4-
fluorophenyl)-1H-pyrazole-3-carbonitrile (10)
HRMS (EI): calcd. for C18H12Cl2F3N4O (M+): 427.0335; found:
427.0313.
Light yellow solid; mp 209–211 8C.
1H NMR (500 MHz, DMSO): 8.21 (s, 2H), 7.55–7.53 (m, 2H), 7.32
(t, J = 7.5, 2H) 6.23 (s, 2H).
5-Amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4-p-
tolyl-1H-pyrazole-3-carbonitrile (5)
13C NMR (500 MHz, DMSO): 161.1 (J = 242.5), 146.3, 135.9,
135.8, 132.8 (J = 33.75), 129.4 (J = 7.5), 126.5, 126.0, 124.7,
122.3 (J = 271.25), 116 (J = 21.25), 114.3, 104.1.
HRMS (EI): calcd. for C17H9Cl2F4N4 (M+): 415.0135; found:
415.0141.
Light yellow solid; mp 203–205 8C.
1H NMR (500 MHz, DMSO): 8.30 (s, 2H), 7.47 (d, J = 5 Hz, 2H),
7.36 (d, J = 5 Hz, 2H), 6.22 (s, 2H), 2.41 (s, 3H).
13C NMR (500 MHz, DMSO): 146.2, 136.2, 135.9, 132.7
(J = 33.75 Hz), 129.5, 127.2, 126.8, 126.6, 126.5, 124.6, 122.4
(J = 271.25 Hz), 114.5, 104.9, 20.7.
5-Amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4-(4-
(trifluoromethyl)phenyl)-1H-pyrazole-3-carbonitrile (11)
HRMS (EI): calcd. for C18H12Cl2F3N4 (M+): 411.0386; found:
411.0368.
Light yellow solid; mp 208–210 8C.
1H NMR (500 MHz, DMSO): 8.26 (s, 2H), 7.85 (d, J = 10 Hz, 2H),
7.75 (d, J = 10 Hz, 2H), 6.47 (s, 2H).
5-Amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4-(4-
ethylphenyl)-1H-pyrazole-3-carbonitrile (6)
13C NMR (500 MHz, DMSO): 146.9, 135.9, 134.8 (J = 202.5 Hz),
132.9 (J = 33.75 Hz), 127.7, 126.1 (J = 201.3 Hz), 126.6, 126.5,
125.9, 125.8, 124.7, 123.3 (J = 30 Hz), 114.1, 103.4.
HRMS (EI): calcd. for C18H9Cl2F6N4 (M+): 465.0103; found:
465.0075.
Light yellow solid; mp 206–208 8C.
1H NMR (500 MHz, DMSO): 8.24 (s, 2H), 7.44 (d, J = 10 Hz, 2H),
7.34 (d, J = 10 Hz, 2H), 6.17 (s, 2H), 2.67 (q, 2H), 1.22 (t, 3H).

48
T. Lv et al. / Journal of Fluorine Chemistry 137 (2012) 44–49
4-(2-Chlorophenyl)-3-methyl-1-phenyl-1H-pyrazol-5-
5-Amino-1-(2-chloro-4-(trifluoromethyl)phenyl)-4-phenyl-
amine (18)
1H-pyrazole-3-carbonitrile (12)
Brown oil.
Light yellow solid; mp 180–182 8C.
1H NMR (500 MHz, DMSO): 7.62–7.32 (m, 9H), 4.92 (s, 2H), 1.99
(s, 3H).
1H NMR (500 MHz, DMSO): 8.09–7.96 (m, 3H), 7.54–7.33 (m,
5H), 6.01 (s, 2H).
13C NMR (500 MHz, DMSO): 146.6, 143.8, 133.8, 132.9, 131.6,
131.5, 129.5, 129.1, 128.6, 127.2, 126.1, 122.7, 102.0, 12.7.
HRMS (EI): calcd. for C16H15ClN3 (M+):284.0949; found:
284.0948.
13C NMR (500 MHz, DMSO): 146.1, 136.3, 135.1, 131.7
(J = 33.75 Hz), 129.7, 129.2, 129.0, 128.6, 127.6, 127.5, 127.2,
126.9, 123.7 (J = 271.25), 114.6, 105.5.
HRMS (EI): calcd. for C17H11ClF3N4 (M+): 363.0619; found:
363.0622.
4-(4-Fluorophenyl)-3-methyl-1-phenyl-1H-pyrazol-5-
amine (19)
3-Methyl-1, 4-diphenyl-1H-pyrazol-5-amine (13)
Brown oil.
1H NMR (500 MHz, DMSO): 7.53–7.22 (m, 9H), 5.03 (s, 2H), 2.14
(s, 3H).
Brown oil.
1H NMR (500 MHz, DMSO): 7.60–7.23 (m, 10H), 5.01 (s, 2H),
2.16 (s, 3H).
13C NMR (500 MHz, DMSO): 160.3 (J = 240 Hz), 146.0, 143.3,
138.8, 130.2 (J = 7.5 Hz), 129.2, 128.6, 126.4, 123.2, 115.4
(J = 21.3 Hz), 102.9, 13.4.
13C NMR (500 MHz, DMSO): 145.0, 143.2, 138.8, 133.2, 129.1,
128.6, 128.2, 126.3, 125.4, 123.1, 103.7, 13.0.
HRMS (EI): calcd. for C16H16N3 (M+): 250.1339; found:
250.1342.
HRMS (EI): calcd. for C16H15FN3 (M+): 268.1245; found:
268.1248.
4-(4-Chlorophenyl)-3-methyl-1-phenyl-1H-pyrazol-5-
amine (20)
4-(4-Methoxyphenyl)-3-methyl-1-phenyl-1H-pyrazol-5-
amine (14)
Brown oil.
Brown oil.
1H NMR (500 MHz, DMSO): 7.58–7.33 (m, 9H), 5.11 (s, 2H), 2.15
(s, 3H).
1H NMR (500 MHz, DMSO): 7.59–6.99 (m, 9H), 4.89 (s, 2H), 3.77
(s, 3H), 2.12 (s, 3H).
13C NMR (500 MHz, DMSO): 146.0, 143.4, 138.7, 132.2, 129.9,
129.2, 128.5, 126.4, 125.9, 123.2, 102.5, 13.0.
HRMS (EI): calcd. for C16H15ClN3 (M+): 284.0949; found:
284.0946.
13C NMR (500 MHz, DMSO): 157.2, 146.0, 142.9, 138.9, 131.5,
129.6, 129.1, 128.6, 122.9, 114.1, 103.6, 55.0, 13.4.
HRMS (EI): calcd. for C17H18N3O (M+): 280.1444; found:
280.1456.
Acknowledgements
3-Methyl-1-phenyl-4-p-tolyl-1H-pyrazol-5-amine (15)
The authors thank the National Natural Science Foundation of
China (No. 20972114), Zhejiang Provincial Natural Science
Foundation of China (Y4100578) and the Opening Foundation of
Zhejiang Provincial Top Key Discipline (100061200140).
Brown oil.
1H NMR (500 MHz, DMSO): 7.60–7.22 (m, 9H), 4.94 (s, 2H), 2.32
(s, 3H), 2.14 (s, 3H).
13C NMR (500 MHz, DMSO): 146.0, 143.1, 138.9, 134.5, 130.2,
129.2, 129.1, 128.2, 126.2, 123.0, 103.7, 20.5, 13.0.
HRMS (EI): calcd. for C17H18N3 (M+): 264.1495; found:
264.1504.
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264.1508.

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