Facile synthesis of novel CF3-substituted ring-fused furo[2,3-c]pyrazoles through Rh2(OAc)4 catalyzed [3+2] cycloaddition of 4-diazo-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5(4H)-one with aromatic alkynes

Article abstract of DOI:10.1016/j.tet.2011.09.007

The Rh₂(OAc)₄ catalyzed [3+2] cycloaddition of 4-diazo-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5(4H)-one with aromatic alkynes was studied, and this protocol can be efficiently applied to the synthesis of the novel CF₃-sub

Full text of DOI:10.1016/j.tet.2011.09.007

Tetrahedron 67 (2011) 8496e8501
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Facile synthesis of novel CF3-substituted ring-fused furo[2,3-c]pyrazoles through
Rh2(OAc)4 catalyzed [3þ2] cycloaddition of 4-diazo-1-phenyl-3-(trifluoromethyl)-
1H-pyrazol-5(4H)-one with aromatic alkynes
*
Zhenhua Zhang, Jianwei Han, Shizheng Zhu
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 18 May 2011
Received in revised form 31 August 2011
Accepted 6 September 2011
Available online 10 September 2011
The Rh2(OAc)4 catalyzed [3þ2] cycloaddition of 4-diazo-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5(4H)-
one with aromatic alkynes was studied, and this protocol can be efficiently applied to the synthesis of the
novel CF3-substituted ring-fused furo[2,3-c]pyrazoles.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Ring-fused heterocycles
Cycloaddition
Fluorine-containing compounds
Rhodium acetate dimmer
1. Introduction
recognized as important precursor in synthetic organic chemistry
for highly reactive metal carbenoids, particularly with copper8 and
Pyrazoles, one of the most valuable N-heterocyclic com-
pounds, attract attentions due to their wide range of pharmaco-
logical proprieties.1 They are present in leading drugs, such as
Viagra1a and Celebrex,1b therefore, are considered very important
for pharmaceutical industries. Pyrazolo[3,4-d]pyrimidines of type
A (Fig. 1) show inhibition properties towards Src in a cell-free
assay, as well as antiproliferative activity towards the epider-
moid (A431) and breast cancer (BC-8701) cell line.2 Thieno[2,3-c]
pyrazoles B (Fig. 1) are an important class of potent kinase in-
hibitors.3 Furo[2,3-c]pyrazoles C (Fig. 1) are an important struc-
tural unit of cyanine dyes4 and have been screened in vitro for
antibacterial and antifungal activities.5 It is well known that, the
introduction of fluorine atoms into a medicinal molecule can
often bring some unpredictable influence on its bioactivity.6 But,
how to efficiently and selectively introduce the fluorine-
containing group into the ring-fused structure is an often met
problem. Therefore, the preparation of pyrazole-fused ring de-
rivatives is very important and challenging from a synthetic point
of view.
rhodium.9The Rh(II)-catalyzed reactions have been well-
established as powerful approaches to generate Rh(II) carbene
species, which promote a number of unique transformations in-
cluding addition,10 CeH insertion11 and ylide formation.12 Despite
a number of synthetic methods available for ring-fused pyrazoles,13
few studies using a-diazocarbonyl compounds in the synthesis of
CF3-substituted ring-fused pyrazoles have also been reported.14
Our research group has a long-standing interest in exploring
the reaction of CF3-substituted diazocompounds.15 Herein, we
wish to report a method for the synthesis of CF3-substituted ring-
fused furopyrazoles based on Rh catalyzed [3þ2] cycloaddition of
CF3-substituted diazocarbonyl compound with aromatic alkynes
(in Scheme 1).
R1
R3
S
R3
O
R2
R2
R4
R4
N
N
N
N
N
N
N
a
-Diazocarbonyl compounds have been extensively studied for
N
their synthetic applications over the last few decades.7 They are
R1
R1
R2
A
B
C
* Corresponding author. E-mail address: zhusz@mail.sioc.ac.cn (S. Zhu).
Fig. 1. Ring-fused pyrazoles AeC.
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.09.007

Z. Zhang et al. / Tetrahedron 67 (2011) 8496e8501
8497
Ph
Ν
Ν
Ph
N
N
F3C
Rh2(OAc)4 (1mol%)
Ar
Ο
+
F3C
O
Toluene /reflux
Ar
N2
4(a-m)
3(a-m)
2
Scheme 1. Rh catalyzed diazocompound with aromatic alkynes.
2. Results and discussions
With the optimized reaction condition in hand (Table 2, entry 4),
a series of aromatic alkynes (3aem) were subjected to diazo-
compound 2 in the presence of Rh2(OAc)4 to synthesize the cor-
responding CF3-substituted ring-fused furo[2,3-c]-pyrazoles
(4aem) in good yields. All the results are summarized in Table 3.
The structure of these novel CF3-substituted ring-fused heterocy-
cles are fully characterized by spectral methods. For the compound
4j, it was further confirmed by X-ray diffraction analysis (in Fig. 2).
Starting material 2 was prepared by diazo-transfer reaction
from the corresponding 1-phenyl-3-trifluoromethyl-2-pyrazolin-5-
one 1.16 Initially, We set out to improve the yield by screening
several diazo transfer reagents and solvents (Table 1). Whereas
arylsulfonyl azides, such as p-tuoluenesulfonyl azide and p-nitro-
benzenesulfonyl azide resulted in poor yields (Table 1, entries 1 and
2) and require longer time, polyfluoroalkanesulfonyl azides gave
improved yields and efficiency (Table 1, entries 3, 4 and 5). Also,
solvents screening identified that dichloromethane is the best
solvent for this transformation.
Secondly, we optimized conditions for the Rh catalyzed [3þ2]
cycloaddition. Under nitrogen, the reaction of CF3-substituted
diazocompound (2) with phenylacetylene (3a) was systematically
examined under different reaction conditions, which was outlined
in Table 2. It was found that 1 mol % Rh2 (OAc)4 was effective to
catalyze this reaction. Among several solvents examined, toluene
was turned out to be the best one.
Table 3
Rh catalyzed [3þ2] cycloaddition of 2 with 3
Entry
3
Time (h)
8
4
Yielda (%)
82
1
4a
2
8
4b
56
Table 1
Optimization of diazo-transfer reactiona
3
4
8
8
4c
75
97
4d
Yieldb (%)
5
8
4e
50
Entry
R
Time
Solvent
1
2
3
4
5
6
7
8
p-CH3C6H4
p-NO2C6H4
I(CF2)2O(CF2)2
C4F9
1.5 h
1.5 h
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Et2O
47
56
89
91
87
83
86
79
8 min
8 min
8 min
8 min
8 min
8 min
6
7
8
8
4f
72
61
Cl(CF2)4
I(CF2)2O(CF2)2
I(CF2)2O(CF2)2
I(CF2)2O(CF2)2
CH3CN
THF
4g
a
Molar ratio of 1: diazo transfer reagent: Et3N¼1:1:1.
b
Isolated yield.
Table 2
8
9
8
8
4h
4i
57
69
Screening the reaction conditionsa
Entry
Cat. (mol %)
Solvent
Temp
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
d
Toluene
CH2Cl2
Et2O
Toluene
CH3CN
THF
1,4-Dioxane
Benzene
HCCl3
ClCH2CH2Cl
Toluene
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
8
16
11
8
15
20
20
12
15
10
6
d
Rh2 (OAc)4 (1)
Rh2 (OAc)4 (1)
Rh2 (OAc)4 (1)
Rh2 (OAc)4 (1)
Rh2 (OAc)4 (1)
Rh2 (OAc)4 (1)
Rh2 (OAc)4 (1)
Rh2 (OAc)4 (1)
Rh2 (OAc)4 (1)
Rh2 (OAc)4 (2)
38
29
82
10
d
27
43
47
25
85
10
11
8
8
4j
72
66
9
10
11
4k
a
Molar ratio of 2/3a¼1:1.
b
Isolated yield.
(continued on next page)

8498
Z. Zhang et al. / Tetrahedron 67 (2011) 8496e8501
ꢀ10 ꢁC and then slowly brought to room temperature. The solvent
Table 3 (continued )
Yielda (%)
89
was then removed under reduced pressure and the crude material
Entry
3
Time (h)
8
4
was purified by flash chromatography.
12
13
4l
4.2.1. 4-Diazo-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5(4H)-one
(2).
8
4m
57
a
Isolated yield.
Orange solid; Mp: 98e99 ꢁC. 1H NMR (300 MHz, CDCl3):
d¼7.86
(d, J¼8.4 Hz, 2H), 7.45 (t, J¼7.8 Hz, 2H), 7.26e7.32 (m, 1H). 19F NMR
(282 MHz, CDCl3):
d
¼ꢀ63.76 (s, CF3). 13C NMR (100 MHz, CDCl3):
d
¼161.7, 137.5, 132.3 (q, 2JCF3¼40.8 Hz), 129.0, 126.6, 119.8, 118.6 (q,
1JCF3¼266.9 Hz). IR (KBr): v¼2146, 1702, 1594, 1540, 1480, 1364,
1299, 1196, 1147, 988, 913, 823, 758, 723, 690. MS: m/z(%)¼254 (Mþ,
76), 228 (10), 105 (17), 77 (100), 51 (17). HRMS (EI) calcd for
C10H5F3N4O: 254.0415; found: 254.0415.
4.3. General procedure for the synthesis of compounds 3
Under nitrogen atmosphere, to a dry Schlenk tube containing
Rh2(OAc)4 (4 mg, 1 mol %), phenylacetylenes 1 (1.2 equiv) and tol-
uene (5 mL), a solution of CF3-substituted diazocompound 2
(254 mg, 1 mmol) in 2 mL toluene was added by a syringe pump.
After addition, the reaction mixture was stirred at reflux temper-
ature for about 8 h, until the starting material of CF3-substituted
diazocompound disappeared while monitoring by TLC. The solvent
was removed in vacuum and the residue was purified on silica gel
using petroleum ether/ethyl acetate (20:1) as eluent to afford the
corresponding products.
Fig. 2. X-ray crystal structure of 4j.
3. Conclusions
In summary, we developed a convenient method for preparation
of novel CF3-substituted ring-fused furo[2,3-c]pyrazoles through
Rh2(OAc)4 catalyzed [3þ2] cycloaddition of diazocarbonyl com-
pounds with aromatic alkynes. They are important structural units
in pigments and dyes with remarkable biological activities and
useful building blocks in organic synthesis. Therefore, applications
in medicinal chemistry call for other studies, which will be reported
in due course.
4.3.1. 1,5-Diphenyl-3-(trifluoromethyl)-1H-furo[2,3-c]pyrazole (4a).
4. Experimental section
4.1. General remarks and methods
Melting points were measured in Temp-Melt apparatus and
uncorrected, 1H and 19F NMR spectra were recorded in CDCl3 on
Bruker AM-300 or AM-400 instruments with Me4Si and CFCl3 (with
upfield negative) as the internal and external standards, re-
spectively. IR spectra were obtained with a Nicolet AV-360 spec-
trophotometer. Lower resolution mass spectra or high-resolution
mass spectra (HRMS) were obtained on a FinniganMAT-8430 in-
strument using the electron impact ionization technique (70 eV). X-
ray diffraction crystal structure analysis was obtained on Bruker P4
instrument. All reaction as well as column chromatography were
monitored routinely with the aid of TLC or 19F NMR spectroscopy.
White solid; Mp: 157e158 ꢁC. 1H NMR (300 MHz, CDCl3):
¼8.00 (d, J¼8.1 Hz, 2H), 7.76 (d, J¼7.8 Hz, 2H), 7.56 (t,
d
J¼7.1 Hz, 2H), 7.47 (t, J¼7.1 Hz, 2H), 7.36e7.40 (m, 2H), 6.90 (s,
1H). 19F NMR (CDCl3, 282 MHz):
d
¼ꢀ61.84 (s, 3F). 13C
NMR (100 MHz, CDCl3):
d
¼159.0, 154.6, 137.3, 131.8 (q,
4.2. General procedure for the synthesis of compounds 2
2JCF3¼40.1 Hz), 129.9, 129.6, 128.9, 128.7, 127.0, 124.1, 121.0 (q,
3
1JCF3¼266.9 Hz), 118.2, 112.0 (m, JCF3¼2.2), 97.6. IR (KBr):
Et3N (1.0 equiv) was added by a syringe pump dropwise to the
v¼1603, 1577, 1508, 1485, 1456, 1442, 1417, 1195, 1120, 1070,
735, 686. MS: m/z(%)¼328 (Mþ, 100), 259 (35), 231 (32), 180
(24), 128 (33), 102 (19), 77 (73). HRMS (EI) calcd for
C18H11F3N2O: 328.0823; found: 328.0828.
solution of 1-phenyl-3-trifluoromethyl-2-pyrazolin-5-one
1
(1.0 equiv) and I(CF2)2O(CF2)2SO2N3 (1.0 equiv) in CH2Cl2 at ꢀ10 ꢁC.
The resulting deep red-coloured solution was stirred for 8 min at

Z. Zhang et al. / Tetrahedron 67 (2011) 8496e8501
8499
4.3.2. 1-Phenyl-5-o-tolyl-3-(trifluoromethyl)-1H-furo[2,3-c]pyrazole
(4b).
White solid; Mp: 166e167 ꢁC. 1H NMR (300 MHz, CDCl3):
d¼7.96
(d, J¼8.1 Hz, 2H), 7.59 (d, J¼7.8 Hz, 2H), 7.52 (t, J¼8.1 Hz, 2H), 7.33 (t,
J¼7.5 Hz, 1H), 7.22 (d, J¼8.1 Hz, 2H), 6.77 (s, 1H), 2.37 (s, 3H). 19F
NMR (CDCl3, 282 MHz):
d
¼ꢀ61.79 (s, 3F). 13C NMR (100 MHz,
CDCl3):
d
¼159.3, 154.5, 138.8, 137.4, 131.7 (q, 2JCF3¼40.1 Hz), 129.6,
129.5, 127.2, 127.0, 124.0, 121.1 (q, 1JCF3¼267.1 Hz), 118.2, 112.0 (m,
3JCF3¼1.5), 96.8, 21.3. IR (KBr): v¼1602, 1569, 1454, 1416, 1366, 1331,
1044, 910, 778, 753. MS: m/z(%)¼342 (Mþ, 100), 343 (19), 273 (47),
245 (28), 194 (21), 128 (27), 119 (18), 77 (54). HRMS (EI) calcd for
C19H13F3N2O: 342.0980; found: 342.0978.
4.3.5. 5-(4-Methoxyphenyl)-1-phenyl-3-(trifluoromethyl)-1H-furo
[2,3-c]pyrazole (4e).
White solid; Mp: 144e145 ꢁC. 1H NMR (300 MHz, CDCl3):
d
¼7.98
(d, J¼8.1 Hz, 2H), 7.70e7.73 (m, 1H), 7.52 (t, J¼7.8 Hz, 2H), 7.31e7.36
(m, 4H), 6.73 (s, 1H), 2.56 (s, 3H). 19F NMR (CDCl3, 282 MHz):
d
¼ꢀ62.24 (s, 3F). 13C NMR (100 MHz, CDCl3):
¼158.8, 154.4, 137.4,
d
135.6, 131.7 (q, 2JCF3¼40.1 Hz), 131.4, 129.6, 129.3, 129.0, 127.9, 126.9,
126.3, 121.1 (q, 1JCF3¼267.1 Hz), 118.1, 112.1 (m, 3JCF3¼1.5), 101.3, 21.8.
IR (KBr): v¼1598, 1576, 1507, 1487, 1416, 1193, 1176, 1070, 1508, 754,
734. MS: m/z(%)¼342 (Mþ, 100), 343 (21), 273 (43), 194 (29), 128
(32), 116 (19), 91 (18), 77 (69). HRMS (EI) calcd for C19H13F3N2O:
342.0980; found: 342.0981.
4.3.3. 1-Phenyl-5-m-tolyl-3-(trifluoromethyl)-1H-furo[2,3-c]
pyrazole (4c).
White solid; Mp: 128e129 ꢁC. 1H NMR (300 MHz, CDCl3):
d¼7.98
(d, J¼8.1 Hz, 2H), 7.67 (d, J¼8.4 Hz, 2H), 7.53 (t, J¼7.7 Hz, 2H), 7.34
(m, 1H), 6.97 (d, J¼7.8 Hz, 2H), 6.72 (s, 1H), 3.86 (s, 3H). 19F NMR
(CDCl3, 282 MHz):
d
¼ꢀ61.72 (s, 3F). 13C NMR (100 MHz, CDCl3):
2
d
¼160.1, 159.2, 154.4, 137.4, 131.6 (q, JCF3¼40.1 Hz), 129.6, 126.9,
1
125.7, 122.7, 121.1 (q, JCF3¼266.9 Hz), 118.2, 114.4, 112.1 (m,
3JCF3¼2.2), 96.0, 55.4. IR (KBr): v¼1599, 1559, 1546, 1483, 1456,
1306, 1197, 1119, 1071, 829, 752. MS: m/z(%)¼358 (Mþ, 60), 290 (15),
289 (67), 210 (26), 135 (35), 128 (20), 77 (100), 51 (25). HRMS (EI)
calcd for C19H13F3N2O2: 358.0929; found: 358.0926.
White solid; Mp: 109e110 ꢁC. 1H NMR (300 MHz, CDCl3):
d¼7.91
4.3.6. 5-(3-Methoxyphenyl)-1-phenyl-3-(trifluoromethyl)-1H-furo
[2,3-c]pyrazole (4f).
(d, J¼7.8 Hz, 2H), 7.45e7.51 (m, 4H), 7.25e7.32 (m, 2H), 7.08e7.11
(m, 1H), 6.75 (s, 1H), 2.37 (s, 3H). 19F NMR (CDCl3, 282 MHz):
d
¼ꢀ62.57 (s, 3F). 13C NMR (100 MHz, CDCl3):
¼159.2, 154.5, 138.7,
d
137.3, 131.7 (q, 2JCF3¼40.1 Hz), 129.8, 129.6, 128.8, 126.9, 124.6, 121.3,
1
3
121.1 (q, JCF3¼267.6 Hz), 118.2, 112.0 (m, JCF3¼2.2), 97.4, 21.5. IR
(KBr): v¼1600, 1578, 1508, 1455, 1413, 1195, 1117, 1070, 748, 686.
MS: m/z(%)¼342 (Mþ, 60), 273 (35), 243 (25), 187 (100), 186 (36),
132 (37), 128 (30), 77 (76). HRMS (EI) calcd for C19H13F3N2O:
342.0980; found: 342.0985.
4.3.4. 1-Phenyl-5-p-tolyl-3-(trifluoromethyl)-1H-furo[2,3-c]pyrazole
(4d).
White solid; Mp: 118e119 ꢁC. 1H NMR (300 MHz, CDCl3):
d¼7.97
(d, J¼8.1 Hz, 2H), 7.54 (t, J¼7.1 Hz, 2H), 7.31e7.37 (m, 3H), 7.26 (s,
1H), 6.86e6.91 (m, 2H), 3.88 (s, 3H). 19F NMR (CDCl3, 282 MHz):
d
¼ꢀ61.71 (s, 3F). 13C NMR (100 MHz, CDCl3):
d
¼156.0, 158.8, 154.5,
2
137.3, 131.7 (q, JCF3¼40.1 Hz), 131.1, 130.0, 129.6, 126.9, 121.0 (q,
1JCF3¼266.9 Hz), 118.1, 116.6, 113.9, 112.0 (m, JCF3¼1.5), 109.9, 97.8,
3
55.3. IR (KBr): v¼3017,1578,1546,1508,1457,1328,1315,1286,1179,
1157, 1071, 1040. MS: m/z(%)¼358 (Mþ, 100), 359 (22), 289 (34), 210
(12), 132 (16), 128 (21), 77 (47), 51 (11). HRMS (EI) calcd for
C19H13F3N2O2: 358.0929; found: 358.0923.

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Z. Zhang et al. / Tetrahedron 67 (2011) 8496e8501
White solid; Mp: 167e168 ꢁC. 1H NMR (300 MHz, CDCl3):
d¼7.97
4.3.7. 5-(4-Fluorophenyl)-1-phenyl-3-(trifluoromethyl)-1H-furo[2,3-
c]pyrazole (4g).
(d, J¼7.8 Hz, 2H), 7.52e7.59 (m, 6H), 7.34e7.39 (m, 1H), 6.89 (s, 1H).
19F NMR (CDCl3, 282 MHz):
CDCl3):
d
¼ꢀ61.82 (s, 3F). 13C NMR (100 MHz,
2
d
¼157.8, 154.5, 137.2, 132.2, 131.8 (q, JCF3¼40.8 Hz), 129.6,
128.8, 127.1, 125.4, 122.7, 120.9 (q, 1JCF3¼266.8 Hz), 118.1, 112.1 (m,
3JCF3¼2.2), 98.2. IR (KBr): v¼1601, 1581, 1479, 1453, 1412, 1188, 1120,
1070, 1043, 998, 871. MS: m/z(%)¼406 (Mþ, 89), 407 (26) 408 (86),
337 (32), 339 (29), 258 (33), 128 (66), 77 (100). HRMS (EI) calcd for
C18H10BrF3N2O: 405.9929; found: 405.9932.
4.3.10. 5-(3-Chlorophenyl)-1-phenyl-3-(trifluoromethyl)-1H-furo
[2,3-c]pyrazole (4j).
White solid; Mp: 182e183 ꢁC. 1H NMR (300 MHz, CDCl3):
d¼7.96
(d, J¼7.8 Hz, 2H), 7.69e7.74 (m, 2H), 7.54 (t, J¼7.8 Hz, 2H), 7.33e7.38
(m, 1H), 7.15 (t, J¼8.7 Hz, 2H), 6.81 (s, 1H). 19F NMR (CDCl3,
282 MHz):
CDCl3)
d
¼ꢀ61.78 (s, 3F), ꢀ111.44 (s, 1F). 13C NMR (100 MHz,
d
¼162.9 (d, 1JF¼247.9 Hz), 158.1, 154.6, 137.3, 131.8 (q,
2JCF3¼40.1 Hz), 129.7, 127.1, 126.3 (d, 4JF¼3.7 Hz), 126.1 (d,
3JF¼8.1 Hz), 121.0 (q, 1JCF3¼267.1 Hz), 118.3, 116.2 (d, 2JF¼21.9 Hz),
3
112.0 (m, JCF3¼2.2), 97.4 ppm. IR (KBr): v¼1599, 1580, 1496, 1484,
1253, 1121, 1101, 847, 816. MS: m/z(%)¼346 (Mþ, 78), 277 (42), 249
(25), 198 (43), 128 (57), 123 (23), 77 (100), 51 (35). HRMS (EI) calcd
for C18H10F4N2O: 346.0729; found: 346.0727.
White solid; Mp: 131e132 ꢁC. 1H NMR (300 MHz, CDCl3):
d¼7.96
(d, J¼7.8 Hz, 2H), 7.70 (s, 1H), 7.52e7.61 (m, 3H), 7.30e7.39 (m, 3H),
4.3.8. 5-(2-Fluorophenyl)-1-phenyl-3-(trifluoromethyl)-1H-furo[2,3-
c]pyrazole (4h).
6.89 (s, 1H). 19F NMR (CDCl3, 282 MHz):
d
¼ꢀ61.77 (s, 3F). 13C NMR
(100 MHz, CDCl3):
d
¼157.3, 154.5, 137.1, 135.1, 131.9 (q,
2JCF3¼40.1 Hz), 131.5, 130.2, 129.6, 128.6, 127.1, 123.9, 122.0, 120.8 (q,
1JCF3¼267.6 Hz), 118.1, 111.8 (m, JCF3¼1.5), 98.7. IR (KBr): v¼1601,
3
1574, 1507, 1484, 1339, 1119, 1070, 1044, 901, 785, 757. MS: m/z(%)¼
362 (Mþ), 342 (90), 273 (44), 245 (28), 194 (30), 128 (49), 91 (28), 77
(100). HRMS (EI) calcd for C18H10ClF3N2O: 362.0434; found:
362.0435.
Crystal data of 4j. C18H10ClF3N2O: Mw¼362.73, CCDC reference
number is no. 816716, orthorhombic, space group P2(1)2(1)2(1),
ꢀ
a¼4.7199(4), b¼15.3676(14), c¼21.928(2) A,
a¼90,
b¼90,
g
¼90,
3
ꢀ
3
V¼1590.5(2) A , Z¼4, Dc¼1.515 mg/m , F (000)¼736, radiation, Mo
ꢀ
Ka
(l
¼0.7107 A), 4.556ꢂ2
q
ꢂ48.261, intensity data were collected at
White solid; Mp: 161e162 ꢁC. 1H NMR (300 MHz, CDCl3):
296 K with a Bruker axis D8 diffractometer, and employing
u
/2q
d
¼7.95e7.97 (m, 2H), 7.49e7.57 (m, 3H), 7.32e7.44 (m, 3H), 7.02e7.07
scanning technique, in the range of ꢀ5ꢂhꢂ5, ꢀ18ꢂkꢂ18,
(m, 1H), 6.89 (s, 1H). 19F NMR (CDCl3, 282 MHz):
d
¼ꢀ61.89 (s, 3F),
ꢀ22ꢂlꢂ27.
ꢀ111.82 (s,1F).13C NMR (100 MHz, CDCl3):
d
¼163.2 (d, 1JF¼245.0 Hz),
157.6 (d, 4JF¼2.9 Hz),154.6, 137.2, 132.0 (q, JCF3¼40.1 Hz), 131.9 (d,
3JF¼8.0 Hz), 130.7 (d, 3JF¼8.7 Hz), 129.7, 127.2, 120.9 (q,
1JCF3¼266.9 Hz), 119.7 (d, 4JF¼2.9 Hz), 118.3, 115.6 (d, 2JF¼21.1 Hz),
111.9 (m, 3JCF3¼1.5), 111.1 (d, 2JF¼23.3 Hz), 98.8 ppm; IR (KBr): v¼1615,
1599, 1582, 1488, 1456, 1416, 1137, 1117, 1045, 985, 956. MS: m/z(%)¼
346 (Mþ,100), 347 (21), 334 (32), 277 (35), 249 (32),198 (23),128 (56),
77 (97). HRMS (EI) calcd for C18H10F4N2O: 346.0729; found: 346.0732.
2
4.3.11. 5-(Naphthalen-2-yl)-1-phenyl-3-(trifluoromethyl)-1H-furo
[2,3-c]pyrazole (4k).
4.3.9. 5-(4-Bromophenyl)-1-phenyl-3-(trifluoromethyl)-1H-furo[2,3-
c]pyrazole (4i).
White solid; Mp: 152e153 ꢁC. 1H NMR (300 MHz, CDCl3):
d
¼8.16
(s, 1H), 8.00 (d, J¼8.1 Hz, 2H), 7.79e7.89 (m, 3H), 7.73 (d, J¼8.7 Hz,
1H), 7.46e7.58 (m, 4H), 7.33e7.38 (m, 1H), 6.93 (s, 1H). 19F NMR
(CDCl3, 282 MHz):
d
¼ꢀ61.75 (s, 3F). IR (KBr): v¼1602, 1574, 1553,
1484, 1411, 1187, 1153, 1132, 1120, 961, 904. MS: m/z(%)¼378 (Mþ,
100), 379 (24), 309 (38), 281 (24), 155 (13), 128 (15), 127 (22), 77
(31). HRMS (EI) calcd for C22H13F3N2O: 378.0980; found: 378.0981.

Z. Zhang et al. / Tetrahedron 67 (2011) 8496e8501
8501
4.3.12. 1-Phenyl-5-(thiophen-2-yl)-3-(trifluoromethyl)-1H-furo[2,3-
c]pyrazole (4l).
(93), 51 (32). HRMS (EI) calcd for C16H9F3N2O2S: 334.0388; found:
334.0392.
Acknowledgements
The authors thank the National Natural Science Foundation of
China (NNSFC) (No. 21032006 and No. 20972178).
Supplementary data
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2011.09.007. These data
include MOL files and InChIKeys of the most important compounds
described in this article.
Yellow solid; Mp: 144e145 ꢁC. 1H NMR (300 MHz, CDCl3):
d
¼7.85 (d, J¼8.4 Hz, 2H), 7.43 (t, J¼7.8 Hz, 2H), 7.22e7.30 (m, 3H),
References and notes
6.97e7.00 (m, J¼1H), 6.60 (s, 1H). 19F NMR (CDCl3, 282 MHz):
d
¼ꢀ62.01 (s, 3F). 13C NMR (100 MHz, CDCl3):
d¼154.2, 137.2, 132.1,
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2
131.7 (q, JCF3¼40.1 Hz), 129.6, 127.9, 127.1, 125.8, 124.4, 121.0 (q,
1JCF3¼266.9 Hz), 118.2, 112.0 (m, JCF3¼1.4), 97.6. IR (KBr): v¼1601,
3
1568, 1455, 1417, 1232, 1117, 1070, 906, 735, 698. MS: m/z(%)¼334
(Mþ, 73), 265 (44), 237 (30), 186 (21), 128 (33), 108 (16), 77 (100), 51
(37). HRMS (EI) calcd for C16H9F3N2O2S: 334.0388; found:
334.0392.
4.3.13. 1-Phenyl-5-(thiophen-3-yl)-3-(trifluoromethyl)-1H-furo[2,3-
c]pyrazole (4m).
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Yellow solid; Mp: 143e144 ꢁC. 1H NMR (300 MHz, CDCl3):
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¼7.94 (d, J¼7.8 Hz, 2H), 7.61 (s,1H), 7.51 (t, J¼7.8 Hz, 2H), 7.30e7.35
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¼ꢀ62.63 (s, 3F).
13C NMR (100 MHz, CDCl3):
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¼155.9, 154.3, 137.3, 132.2 (q,
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2JCF3¼40.1 Hz), 131.6, 129.6, 127.0, 124.4, 121.0 (q, JCF3¼267.6 Hz),
120.8, 118.3, 118.2, 111.8 (m, 3JCF3¼1.5), 97.3. IR (KBr): v¼1602, 1569,
1454, 1366, 1230, 1214, 1117, 1070, 910, 882, 820, 687. MS: m/z(%)¼
334 (Mþ, 100), 335 (20), 265 (35), 237 (33), 128 (47), 111 (22), 77
1