1,3-Dipolar cycloaddition reaction of 3-trifluoromethyl-4- diazopyrazolinones with acetylenedicarboxylates

Article abstract of DOI:10.1016/j.tet.2012.05.062

Refluxing of 3-trifluoromethyl-4-diazopyrazolinones 1 with dimethyl acetylenedicarboxylates 2 in toluene for 48 h afforded trifluoromethyl- substituted pyrazolo [1,5-d][1,2,4]triazin-7-ones, which resulted from the [3+2] dipolar cycloaddition followed by a rearrangement of the initially produced spiro 3H-pyrazole adducts. However, when 1 was heated to 160 °C in dichlorobenzene (o-DCB) for 8 h, it lost nitrogen and reacted with 2 to give 3-trifluoromethyl furo[2,3-c]pyrazoles.

Full text of DOI:10.1016/j.tet.2012.05.062

Tetrahedron 68 (2012) 5969e5978
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journal homepage: www.elsevier.com/locate/tet
1,3-Dipolar cycloaddition reaction of 3-trifluoromethyl-4-diazopyrazolinones
with acetylenedicarboxylates
,
,
*
Zhenhua Zhang a, Xiaowei Wang a, Song Tao a b, Shizheng Zhu a
a Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, China
b Key Laboratory of Eco-chemical Engineering, Ministry of Education, Qingdao University of Science and Technology, Qingdao, Shandong 266042, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Refluxing of 3-trifluoromethyl-4-diazopyrazolinones 1 with dimethyl acetylenedicarboxylates 2 in tol-
uene for 48 h afforded trifluoromethyl-substituted pyrazolo [1,5-d][1,2,4]triazin-7-ones, which resulted
from the [3þ2] dipolar cycloaddition followed by a rearrangement of the initially produced spiro
3H-pyrazole adducts. However, when 1 was heated to 160 ꢀC in dichlorobenzene (o-DCB) for 8 h, it lost
nitrogen and reacted with 2 to give 3-trifluoromethyl furo[2,3-c]pyrazoles.
Received 27 March 2012
Received in revised form 8 May 2012
Accepted 15 May 2012
Available online 23 May 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
3-Trifluoromethyl-4-diazopyrazolinone
Acetylenedicarboxylate
[3þ2] Dipolar cycloaddition
Furo[2,3-c]pyrazole
Pyrazolotriazine
1. Introduction
compounds due to their wide range of pharmacological
propoties.7,8
It is well known that the
a
-diazo carbonyl compounds1e3 play
It was noticed that the preparation and chemical transformation
of fluorine-containing diazopyrazolinones are reported quite lim-
ited. Recently, our group successfully prepared 3-trifluoromethyl-
4-diazopyrazolinones 1 using perfluoroalkane sulfonyl azide as
diazo-transfer reagents.9
a dominant role in dipolar cycloaddition reactions, either through
the diazoalkane moiety or through a reactive intermediate pos-
sessing the stoichiometry of a keto carbene species derived from an
initial loss of nitrogen gas (Scheme 1).
Scheme 1.
a-Diazo carbonyl compounds as a 1,3-dipolar precursor.
4-Diazopyrazolines represent an interesting subclass of this
family of -diazo carbonyl compounds and attracted much at-
tention in recent years. They are widely used to prepare fused
N-heterocyclic compounds,4e6 especially in the synthesis of
ring-fused pyrazoles, which are most valuable N-heterocyclic
Herein, wewishtoreportthereactionresultsof3-trifluoromethyl-
4-diazopyrazolinones 1 with dialkyl acetylenedicarboxylates in dif-
ferent reaction condition.
a
2. Results and discussion
According to our previous reports, starting materials 1aeh were
* Corresponding author. E-mail address: zhusz@mail.sioc.ac.cn (S. Zhu).
prepared by diazo-transfer reaction from the corresponding
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.05.062

5970
Z. Zhang et al. / Tetrahedron 68 (2012) 5969e5978
1-phenyl-3-trifluoromethyl-2-pyrazolin-5-one,10
fluoroalkane sulfonyl azide as diazo-transfer reagents (Table 1).
using
per-
The molecular weigh of 1a and 2a are 254 and 142, respectively. The
elementalanalysisconfirmedthemolecularformulaasC16H11F3N4O5.
Table 1
Preparation of 3-trifluoromethyl-4-diazopyrazolinones 1
Entry
1
Ar
Time (min)
8
Product
Yielda (%)
89
1a
2
8
1b
89
3
4
8
8
1c
90
72
1d
5
6
8
8
1e
1f
91
79
7
8
8
1g
1h
78
78
8
a
Isolated yield.
Cycloadditions of 4-diazo-1-phenyl-3-trifluoromethylpyrazolin-
5-one 1a (1 mmol, 254 mg) with dimethyl acetylenedicarboxylate
MeO2CC^CCO2Me 2a (1.5 mmol, 213 mg) were first performed by
refluxing typically in toluene for a period of 48 h. The product was
isolated as colorless solid in about 25% yield. Recrystallization from
ethanol solution gave fine crystal. It was identified by the spectral
methods and elemental analysis. For example, 19F NMR spectrum of
the product 3a show a singlet peak at ꢁ66.4 ppm comparing with the
starting diazo compound 1a (ꢁ63.9 ppm), it moved to high field
2.5 ppm. In the 1H NMR spectrum, except the phenyl group signal
appeared at 7.53e7.68, two ester methoxyl signal appeared at 3.99
and 4.02 ppm, mass spectrum gave the molecular weigh at 396
(Mþ,76) and fragment peak 365 (MþꢁOCH3, 100) as the base peak.
However, all these analysis data could not rule out the another
possible isomer structure 3a0 (Scheme 2). The product structure
was finally established by single crystal X-ray diffraction analysis to
be dimethyl 4-trifluoromethyl-6-phenyl-7-oxo-6H-pyrazolo[1,5-d]
[1,2,4]triazine-2,3-dicarboxylate. The molecular structure of 3a was
shown in Fig. 1.
It is reasonable to suppose that the stereo and electronic effect is
more favorite to form the spiro-pyrazole adduct C, which then was
rearranged to dimethyl 4-trifluoro-methyl-6-phenyl-7-oxo-6H-
pyrazolo[1,5-d][1,2,4]triazine-2,3-dicarboxylate 3a.
Padwa and co-workers have reported that 4-diazo-3-phenyl-
pyrazolin-5-one when heated with dialkyl acetylenedicarboxylate
at 165 ꢀC for 16e20 h gave the fused pyrazolo[1,5-d][1,2,4]triazine-

Z. Zhang et al. / Tetrahedron 68 (2012) 5969e5978
5971
Scheme 2. The possible reaction pathway.
(Ar¼4-CH3C6H4, R¼Et), it was further confirmed by X-ray diffrac-
tion analysis (Fig. 2).
Although we have reported a Rh2(OAc)4 catalyzed formation of
trifluoromethyl-substituted furo[2,3-c]pyrazoles from the reaction
of 4-diazo-1-phenyll-3-trifluoromethylpyrazolin-5-one with aro-
matic alkynes (Scheme 4), they are different in the types of diazo
decomposition.12
3. Conclusion
In conclusion, we have described two different reaction types of
3-trifluoromethyl-4-diazopyrazolinones
1 in different reaction
conditions. We have successfully developed two different methods
for the preparation of trifluoromethyl-substituted furo[2,3-c]pyr-
azoles in high yields. They are important structural units in pig-
ments and dyes with remarkable biological activities and useful
building blocks in organic synthesis.
4. Experimental section
Fig. 1. X-ray crystal structure of 3a.
4.1. General remarks and methods
7-one ring systems.11 However, in our case when heating of 1 and 2
in 1,2-dichlorobenzene at 160 ꢀC for 6e9 h, the N2 gas was released
and another manner [3þ2] cycloaddition occurred affording tri-
fluoromethyl substituted furo[2,3-c]pyrazoles 4.
Melting points were measured in Temp-Melt apparatus and
uncorrected, 1H and 19F NMR spectra were recorded in CDCl3 on
Bruker AM-300 instruments with Me4Si and CFCl3 (with upfield
negative) as the internal and external standards, respectively. IR
spectra were obtained with a Nicolet AV-360 spectrophotometer.
Lower resolution mass spectra or high-resolution mass spectra
In this reaction, 1 loss the nitrogen gas to form 1,3-dipolar in-
termediate
B
(Scheme 3) and then added to the
acetylenedicarboxylate.
Scheme 3. Reactions of compound 1 with dialkyl acetylenedicarboxylate at 160 ꢀC.
According to the optimized reaction condition, CF3-substituted
ring-fused furo[2,3-c]-pyrazoles (4aaehb) were synthesized in
good yields. All the results are summarized in Table 2. The struc-
tures of these novel CF3-substituted ring-fused heterocycles are
fully characterized by spectral methods. For the compound 4bb
(HRMS) were obtained on a FinniganMAT-8430 instrument 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 rou-
tinely with the aid of TLC or 19F NMR spectroscopy.

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Z. Zhang et al. / Tetrahedron 68 (2012) 5969e5978
Table 2 (continued)
Table 2
Preparation for trifluoromethyl substituted furo[2,3-c]pyrazoles 4
Entry
1aeg (Ar¼)
2aeb Time (h) Product Yielda (%)
Entry
1
1aeg (Ar¼)
2aeb Time (h) Product Yielda (%)
15
2a
2b
8
7
4ha
4hb
69
67
2a
2b
2a
8
8
7
4aa
4ab
4ba
79
82
81
1h
1h
1a
16
2
3
1a
a
Isolated yield.
1b
1b
4.2. General procedure for the synthesis of compounds 1
4
2b
7
4bb
71
Et3N (1.0 equiv) was added by a syringe pump dropwise to the
solution
of
1-phenyl-3-trifluoromethyl-2-pyrazolin-5-one
(1.0 equiv) and I(CF2)2O(CF2)2SO2N3 (1.0 equiv) in CH2Cl2 at
ꢁ10 ꢀC. The resulting deep red-colored solution was stirred for
8 min at ꢁ10 ꢀC and then slowly brought to room temperature. The
solvent was then removed under reduced pressure and the crude
material was purified by flash chromatography.
5
6
7
2a
2b
2a
9
8
7
4ca
4cb
4da
75
82
67
1c
4.2.1. 4-Diazo-1-phenyl-3-trifluoromethylpyrazolin-5-one (1a).
1c
1d
8
2b
2a
2b
8
7
7
4db
4ea
4eb
66
75
72
Orange solid; mp: 98e99 ꢀC. 1H NMR (300 MHz, CDCl3):
d¼7.86
1d
(d, J¼8.4 Hz, 2H), 7.44 (t, J¼7.8 Hz, 2H), 7.28 (t, d, J¼7.2 Hz, 1H). 19F
NMR (282 MHz, CDCl3):
d
¼ꢁ63.76 (s, CF3). 13C NMR (100 MHz,
2
9
CDCl3):
d¼161.7, 137.5, 132.3 (q, JCF3¼40.8 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 (%)¼
254 (Mþ, 76), 228 (10), 105 (17), 77 (100), 51 (17). HRMS (EI) calcd
for C10H5F3N4O: 254.0415; found: 254.0415.
1e
10
1e
4.2.2. 4-Diazo-1-(p-tolyl)-3-trifluoromethylpyrazolin-5-one (1b).
11
12
2a
2b
8
9
4fa
4fb
87
78
1f
1f
13
14
2a
2b
7
7
4ga
4gb
81
73
Orange solid; mp: 88e89 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼7.71
(d, J¼7.2 Hz, 2H), 7.24 (d, J¼8.1 Hz, 2H), 2.37 (s, 3H). 19F NMR
1g
1g
(282 MHz, CDCl3):
d
¼-63.71 (s, CF3). 13C NMR (100 MHz, CDCl3):
d
¼161.8, 136.7, 135.2, 132.1 (q, 2JCF3¼40.9 Hz), 129.6, 120.0, 118.7 (q,
1JCF3¼269.1 Hz), 21.0. IR (KBr): v¼2143, 1701, 1610, 1512, 1479, 1364,
1311, 1226, 1185, 1017, 989, 823. MS: m/z (%)¼268 (Mþ, 39), 269 (5),
119 (12), 92 (9), 91 (100), 89 (6), 65 (18), 41 (5). HRMS (EI) calcd for
C11H7F3N4O: 268.0572; found: 268.0578.

Z. Zhang et al. / Tetrahedron 68 (2012) 5969e5978
5973
Fig. 2. (a) X-ray crystal structure of 4bb and (b) packing map of 4bb.
Scheme 4. Preparation of CF3-substituted furo[2,3-c]pyrazoles by Rh catalysis.
4.2.3. 4-Diazo-1-(4-chlorophenyl)-3-trifluoromethylpyrazolin-5-one
(1c).
Orange solid; mp: 94e95 ꢀC. 1H NMR (300 MHz, CDCl3):
¼8.32 (d, J¼8.4 Hz, 2H), 8.18 (d, J¼8.7 Hz, 2H). 19F NMR
d
(282 MHz, CDCl3):
d
d
¼-63.81 (s, CF3). 13C NMR (100 MHz, CDCl3):
2
¼161.7, 145.3, 142.6, 134.2 (q, JCF3¼41.6 Hz), 124.9, 119.1, 118.4
(q, 1JCF3¼269.1 Hz). IR (KBr): v¼2164, 1702, 1689, 1595, 1542, 1520,
1480, 1353, 1208, 1183, 1163, 1128, 992, 863, 750. MS: m/z (%)¼296
(42), 227 (31), 177 (21), 119 (34), 100 (49), 91 (13), 80 (92), 64
(100). HRMS (EI) calcd for C10H4F3N5O3: 299.0266; found:
299.0269.
4.2.5. 4-Diazo-1-(4-methoxyphenyl)-3-trifluoromethylpyrazolin-5-
one (1e).
Orange solid; mp: 101e102 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼7.85 (d, J¼8.7 Hz, 2H), 7.40 (d, J¼9.0 Hz, 2H). 19F NMR (282 MHz,
CDCl3):
d
¼-63.80 (s, CF3). 13C NMR (100 MHz, CDCl3):
d¼161.6,
2
136.2, 132.8 (q, JCF3¼41.5 Hz), 132.1, 129.2, 120.8, 118.6
(q, 1JCF3¼269.1 Hz). IR (KBr): v¼2139, 1701, 1541, 1480, 1413, 1481,
1364, 1188, 1126, 988, 837. MS: m/z (%)¼288 (Mþ, 42), 290 (14), 141
(9), 139 (28), 113 (31), 111 (100), 75 (29), 50 (8). HRMS (EI) calcd for
C10H4ClF3N4O2: 288.0026; found: 288.0024.
4.2.4. 4-Diazo-1-(4-nitrophenyl)-3-trifluoromethylpyrazolin-5-one
(1d).
Orange solid; mp: 118e119 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼7.72 (d, J¼9.0 Hz, 2H), 6.96 (d, J¼9.0 Hz, 2H), 3.83 (s, 3H). 19F
NMR (282 MHz, CDCl3):
CDCl3):
d
¼ꢁ63.58 (s, CF3). 13C NMR (100 MHz,
d
¼161.7, 158.3, 132.0 (q, 2JCF3¼41.5 Hz), 130.7, 122.0, 118.7
1
(q, JCF3¼268.3 Hz), 114.2, 55.5. IR (KBr): v¼2142, 1694, 1540,
1511, 1480, 1367, 1247, 1176, 1129, 991, 835. MS: m/z (%)¼284
(Mþ, 64), 285 (10), 135 (26), 107 (100), 92 (43), 77 (61), 64 (24),
63 (14). HRMS (EI) calcd for C11H7F3N4O2: 284.0521; found:
284.0520.

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Z. Zhang et al. / Tetrahedron 68 (2012) 5969e5978
4.2.6. 4-Diazo-1-(4-bromophenyl)-3-trifluoromethylpyrazolin-5-one
(1f).
3-trifluoromethylpyrazolin-5-one (1a) (1 mmol, 254 mg) in 10 mL
of toluene at reflux temperature. The reaction mixture was stirred
at this temperature for 48 h. After removing the solvents under
vacuum, the crude product was recrystallized in ethol to give a fine
crystal 3a.
4.3.1. Dimethyl 4-trifluoromethyl-6-phenyl-7-oxo-6H-pyrazolo[1,5-
d][1,2,4]triazine-2,3-dicarboxylate (3a).
Orange solid; mp: 118e119 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼7.80 (d, J¼8.7 Hz, 2H), 7.56 (d, J¼9.0 Hz, 2H). 19F NMR (282 MHz,
CDCl3):
d
¼-63.74 (s, CF3). 13C NMR (100 MHz, CDCl3):
¼161.6,136.7,
d
132.8 (q, 2JCF3¼40.8 Hz), 132.1, 121.1, 119.8, 118.6 (q, 1JCF3¼269.1 Hz).
IR (KBr): v¼2142, 1698, 1542, 1478, 1410, 1362, 1191, 987, 828, 733.
MS: m/z (%)¼332 (Mþ, 45), 334 (45), 185 (25), 183 (28), 157 (94), 155
(100), 76 (51), 75 (44). HRMS (EI) calcd for C10H4BrF3N4O: 331.9521;
found: 331.9526.
Colorless solid; mp 168e169 ꢀC; 1H NMR (300 MHz, CDCl3):
d
¼7.53e7.68 (m, 5H), 4.02 (s, 3H), 3.99 (s, 3H). 19F NMR (282 MHz,
CDCl3):
d
¼ꢁ66.4 (s, CF3); IR (KBr): v¼1686, 1479, 1431, 1381, 1353,
1279, 1179, 1114, 1057, 765, 710. MS: m/z (%)¼396 (Mþ, 76), 365
(100), 183 (7), 119 (25), 91 (10), 77 (28), 51 (17); Anal. Calcd for
C16H11F3N4O5 (%): C, 48.49; H, 2.80; N, 14.14. Found: C, 48.74; H,
2.93; N, 14.05.
4.2.7. 4-Diazo-1-(3-chlorophenyl)-3-trifluoromethylpyrazolin-5-one
(1g).
Crystal data of 3a. C16H11F3N4O5: MW¼396.29. CCDC refer-
ence number is 873114, triclinic, space group Pꢁ1, a¼8.0015(15),
ꢀ
3
b¼10.451(2), c¼11.031(2) A,
a
¼102.843(2),
b
¼102.981(2),
3
ꢀ
g
¼101.811(2), V¼844.4(3) A , Z¼2, Dc¼1.559 mg/m , F (000)¼
ꢀ
404, radiation, Mo K
data were collected at 298 K with a Bruker AXS D8 diffractom-
eter, and employing /2 scanning technique, in the range of
a
(
l
¼0.71073 A), 4.872ꢂ2
q
ꢂ55.567, intensity
u
q
ꢁ9ꢂhꢂ8, ꢁ12ꢂkꢂ12, ꢁ13ꢂlꢂ12.
Orange solid; mp: 74e75 ꢀC. 1H NMR (300 MHz, CDCl3):
d¼7.94
4.4. General procedure for the synthesis of compounds 4
(s, 1H), 7.84 (d, J¼8.4 Hz, 1H), 7.37 (t, J¼8.1 Hz, 1H), 7.26 (d, J¼7.5 Hz,
1H). 19F NMR (282 MHz, CDCl3):
d
¼ꢁ63.90 (s, CF3). 13C NMR
(100MHz, CDCl3):
d
¼161.5,138.6,134.9,132.9(q,2JCF3¼41.6Hz),130.1,
Dimethyl acetylenedicarboxylate 2a (1.5 mmol, 213 mg) was
126.6, 119.5, 118.6 (q, 1JCF3¼269.1 Hz), 117.4. IR (KBr): v¼2145, 1698,
1592, 1471, 1358, 1225, 1191, 1136, 996, 789, 751. MS: m/z (%)¼288
(Mþ, 31), 290 (18), 157 (18), 155 (15), 139 (19), 113 (30), 111 (100), 75
(39). HRMS (EI) calcd for C10H4ClF3N4O2: 288.0026; found: 288.0021.
added in to
a Schlenk flask containing 4-diazo-1-phenyl-3-
trifluoromethylpyrazolin-5-one (1a) (1 mmol, 254 mg) in 10 mL
of 1,2-dichlorobenzene at 160 ꢀC. The reaction mixture was stirred
at this temperature for about 8 h. After removing of solvents under
vacuum, the crude product was further purified by silica gel column
chromatography with acetate/petroleum ether (10:1) to give
product 4aa.
4.2.8. 4-Diazo-1-(2,4-dichlorophenyl)-3-trifluoromethylpyrazolin-5-
one (1h).
4.4.1. Dimethyl 1-phenyl-3-(trifluoromethyl)-1H-furo[2,3-c]pyrazole-
4,5-dicarboxy-late (4aa).
Orange solid; mp: 102e103 ꢀC.1H NMR (300 MHz, CDCl3):
d
¼7.56
(s,1H), 7.38 (s, 2H).19F NMR (282 MHz, CDCl3):
d
¼ꢁ63.83 (s, CF3).13
C
NMR(100 MHz, CDCl3):
d
¼161.9,136.3,133.2 (q, 2JCF3¼41.5Hz),133.1,
132.4,130.6,130.0,128.0,118.5 (q, 1JCF3¼269.0 Hz). IR (KBr): v¼2154,
1713, 1694, 1533, 1476, 1361, 1208, 1188, 1150, 986, 821. MS: m/z
(%)¼322 (Mþ, 37), 324 (25),175 (31),173 (48),147 (64),145 (100),109
(34), 74 (19). HRMS (EI) calcd for C10H3Cl2F3N4O2: 321.9636; found:
321.9634.
White solid; mp: 60 ꢀC. 1H NMR (300 MHz, CDCl3):
d¼7.94
(d, J¼8.1 Hz, 2H), 7.55 (t, J¼7.8 Hz, 2H), 7.39 (t, J¼7.8 Hz, 1H), 3.99
(s, 6H). 19F NMR (CDCl3, 282 MHz):
(100 MHz, CDCl3):
d
¼ꢁ 62.10 (s, 3F). 13C NMR
d
¼161.1, 157.9, 153.5, 146.2, 136.4, 132.7
(q, 2JCF3¼40.8 Hz), 129.8, 127.8, 120.1 (q, 1JCF3¼267.6 Hz), 118.4, 117.7,
112.1 (m, 3JCF3), 53.0. IR (KBr): v¼2924, 2852, 1741, 1729, 1573, 1482,
1457, 1259, 1150, 797,755. MS: m/z (%)¼368 (Mþ, 65), 186 (100), 77
(91), 59 (26), 57 (23), 55 (23), 51 (25), 43 (33). HRMS (EI) calcd for
C16H11F3N2O5: 368.0620; found: 368.0618.
4.3. General procedure for the synthesis of compounds 3
Dimethyl acetylenedicarboxylate 2a (1.5 mmol, 213 mg) was
added in to
a Schlenk flask containing 4-diazo-1-phenyl-

Z. Zhang et al. / Tetrahedron 68 (2012) 5969e5978
5975
4.4.2. Diethyl 1-phenyl-3-(trifluoromethyl)-1H-furo[2,3-c]pyrazole-
4,5-dicarboxylate (4ab).
(s, 3H), 1.42 (t, J¼7.2 Hz, 6H). 19F NMR (CDCl3, 282 MHz):
d
¼ꢁ61.66
(s, 3F). 13C NMR (100 MHz, CDCl3):
d
¼160.9, 157.6, 153.4, 146.2,
137.8, 134.1, 132.3 (q, 2JCF3¼40.1 Hz), 130.3, 120.3 (q, 1JCF3¼267.6 Hz),
3
118.4, 117.8, 109.3 (m, JCF3), 62.4, 62.3, 21.0, 14.1, 13.9. IR (KBr):
v¼2993,1731,1574,1484,1430,1317,1180,1137,1097, 1036, 816, 737.
MS: m/z (%)¼410 (Mþ, 100), 411 (22), 395 (21), 341 (21), 214 (24),
141 (19), 91 (62), 65 (22). HRMS (EI) calcd for C19H17F3N2O5:
410.1090; found: 410.1091.
Crystal data of 4bb. C19H17F3N2O5: Mw¼410.35, CCDC reference
number is 872813, monoclinic, space group P2(1)/c, a¼12.4388(10),
ꢀ
b¼9.1367(7), c¼16.7373(13) A,
a
¼90,
b
¼92.5330(10),
g
¼90,
3
ꢀ
3
V¼1900.3(3) A , Z¼4, Dc¼1.434 mg/m , F (000)¼848, radiation, Mo
ꢀ
Ka
(l
¼0.71073 A), 4.872ꢂ2
q
ꢂ55.567, intensity data were collected
at 293 K with a Bruker AXS D8 diffractometer, and employing
u
/2
q
White solid; mp: 89 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼7.94
scanning technique, in the range of ꢁ14ꢂhꢂ15, ꢁ11ꢂkꢂ10,
ꢁ20ꢂlꢂ18.
(d, J¼8.4 Hz, 2H), 7.55 (t, J¼8.4 Hz, 2H), 7.39 (t, J¼7.2 Hz, 1H), 4.46
(q, J¼6.9 Hz, 4H), 1.42 (t, J¼7.2 Hz, 6H). 19F NMR (CDCl3, 282 MHz):
d
¼ꢁ61.75 (s, 3F). 13C NMR (100 MHz, CDCl3):
d
¼160.9, 157.6,
4.4.5. Dimethyl 1-(4-chlorophenyl)-3-(trifluoromethyl)-1H-furo[2,3-
c]pyrazole-4,5-dicarboxylate (4ca).
2
153.5, 146.3, 136.5, 132.7 (q, JCF3¼40.8 Hz), 129.8, 127.8, 120.2
(q, 1JCF3¼267.6 Hz), 118.5, 117.9, 109.0 (m, 3JCF3), 62.4, 62.3, 14.1, 13.9.
IR (KBr): v¼2988, 2915, 1733, 1599, 1580, 1484, 1454, 1262, 1137,
1118, 1062, 754, 686. MS: m/z (%)¼396 (Mþ, 77), 397 (17), 327 (18),
225 (19), 200 (32), 128 (26), 77 (100), 51 (20). HRMS (EI) calcd for
C18H15F3N2O5: 396.0933; found: 396.0937.
4.4.3. Dimethyl 1-(p-tolyl)-3-(trifluoromethyl)-1H-furo[2,3-c]pyrazole-
4,5-dicarboxylate (4ba).
White solid; mp: 108e109 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼7.90 (d, J¼8.4 Hz, 2H), 7.53 (d, J¼8.7 Hz, 2H), 4.01 (s, 3H), 3.99
(s, 3H). 19F NMR (CDCl3, 282 MHz):
(100 MHz, CDCl3):
d
¼ꢁ62.23 (s, 3F). 13C NMR
d
¼160.9, 157.8, 153.3, 146.4, 134.9, 133.4, 133.1
1
2
(q, JCF3¼41.6 Hz), 130.0, 120.0 (q, JCF3¼268.4 Hz), 119.6, 117.7,
3
109.0 (m, JCF3), 53.0, 52.9. IR (KBr): v¼2924, 1735, 1579, 1482,
1438, 1359, 1285, 1181, 1144, 1109, 1009, 832, 797. MS: m/z (%)¼402
(Mþ, 66), 367 (100), 333 (25), 222 (30), 220 (89), 111 (65), 75 (50),
59 (25). HRMS (EI) calcd for C16H10ClF3N2O5: 402.0230; found:
402.0228.
White solid; mp: 102e103 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼7.80
(d, J¼8.1 Hz, 2H), 7.34 (d, J¼8.1 Hz, 2H), 3.99 (s, 6H), 2.42 (s, 3H). 19F
NMR (CDCl3, 282 MHz):
¼161.2, 158.0, 153.4, 146.1, 137.9, 134.2, 132.4 (q, JCF3¼40.9 Hz),
d
¼ꢁ61.92 (s, 3F).13C NMR (100 MHz, CDCl3):
2
d
4.4.6. Diethyl 1-(4-chlorophenyl)-3-(trifluoromethyl)-1H-furo[2,3-c]
pyrazole-4,5-dicarboxylate (4cb).
130.3,120.2 (q,1JCF3¼267.6 Hz),118.5,117.7,109.0 (m, 3JCF3), 52.9, 21.1.
IR (KBr): v¼2993,1740,1598,1575,1441,1286,1263,1165,1134,1099,
1038, 814. MS: m/z (%)¼382 (Mþ, 100), 383 (21), 381 (26), 367 (20),
313 (22), 200 (81), 91 (56), 65 (28). HRMS (EI) calcd for
C17H13F3N2O5: 382.0777; found: 382.0774.
4.4.4. Diethyl 1-(p-tolyl)-3-(trifluoromethyl)-1H-furo[2,3-c]pyrazole-
4,5-dicarboxylate (4bb).
White solid; mp: 87e88 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼7.90
(d, J¼8.4 Hz, 2H), 7.53 (d, J¼8.7 Hz, 2H), 4.46 (q, J¼7.2 Hz, 4H), 1.42
(t, J¼7.2 Hz, 6H). 19F NMR (CDCl3, 282 MHz):
d
¼ꢁ61.86 (s, 3F). 13
C
NMR (100 MHz, CDCl3):
d
¼160.7, 157.5, 153.4, 146.5, 135.0, 133.4,
133.0 (q, 2JCF3¼41.5 Hz),130.0,129.2,120.9,120.1 (q, 1JCF3¼267.5 Hz),
3
117.9, 109.6 (m, JCF3), 62.5, 62.4, 14.1, 13.9. IR (KBr): v¼2998, 1748,
White solid; mp: 83e84 ꢀC. 1H NMR (300 MHz, CDCl3):
(d, J¼8.1 Hz, 2H), 7.34 (d, J¼8.4 Hz, 2H), 4.45 (q, J¼7.2 Hz, 4H), 2.42
d
¼7.81
1734, 1596, 1574, 1443, 1359, 1159, 1114, 1066, 799, 756. MS: m/z
(%)¼430 (Mþ, 79), 432 (25), 395 (100), 234 (28), 162 (26), 113 (24),

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Z. Zhang et al. / Tetrahedron 68 (2012) 5969e5978
111 (74), 75 (32). HRMS (EI) calcd for C18H14ClF3N2O5: 430.0543;
found: 430.0545.
White solid; mp: 106 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼7.83
(d, J¼9.0 Hz, 2H), 7.05 (d, J¼9.3 Hz, 2H), 3.99 (s, 6H), 3.87
(s, 3H). 19F NMR (CDCl3, 282 MHz):
(100 MHz, CDCl3):
d
¼ꢁ61.79 (s, 3F). 13C NMR
4.4.7. Dimethyl 1-(4-nitrophenyl)-3-(trifluoromethyl)-1H-furo[2,3-c]
pyrazole-4,5-dicarboxylate (4da).
d
¼161.1, 159.0, 157.9, 153.1, 146.0, 132.1
1
2
(q, JCF3¼39.4 Hz), 129.7, 120.2 (q, JCF3¼267.6 Hz), 120.1, 117.7,
3
114.8, 109.2 (m, JCF3), 55.5, 52.9. IR (KBr): v¼2958, 1758, 1577,
1511, 1482, 1430, 1353, 1254, 1179, 1141, 1095, 837,735. MS: m/z
(%)¼398 (Mþ, 100), 383 (26), 329 (52), 216 (78), 92 (32), 77 (40),
57 (25), 40 (38). HRMS (EI) calcd for C17H13F3N2O6: 398.0726;
found: 398.0720.
4.4.10. Diethyl1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-furo[2,3-
c]pyrazole-4,5-dicarboxylate (4eb).
White solid; mp: 147e148 ꢀC. 1H NMR (300 MHz, CDCl3):
d¼8.45
(d, J¼7.8 Hz, 2H), 8.16 (d, J¼8.1 Hz, 2H), 4.03 (s, 3H), 4.01 (s, 3H). 19F
NMR (CDCl3, 282 MHz):
¼160.6, 157.6, 153.6, 146.9, 146.4, 140.7, 134.6 (q, JCF3¼41.6 Hz),
d
¼ꢁ62.73 (s, 3F).13C NMR(100 MHz, CDCl3):
2
d
125.7,122.4 (q,1JCF3¼268.3 Hz),118.4,117.7,110.3 (m, 3JCF3), 53.1, 53.0.
IR (KBr): v¼2925,1757,1732,1598,1480,1409,1344,1162,1042, 861,
749. MS: m/z (%)¼413 (Mþ, 64), 231 (100), 76 (37), 75 (39), 59 (46).
HRMS (EI) calcd for C16H10F3N3O7: 413.0471; found: 413.0474.
4.4.8. Diethyl 1-(4-nitrophenyl)-3-(trifluoromethyl)-1H-furo[2,3-c]
pyrazole-4,5-dicarboxylate (4db).
White solid; mp: 71e72 ꢀC. 1H NMR (300 MHz, CDCl3):
d¼7.82
(d, J¼9.0 Hz, 2H), 7.05 (d, J¼8.7 Hz, 2H), 4.45 (q, J¼7.2 Hz, 4H), 3.87
(s, 3H), 1.41 (t, J¼7.2 Hz, 6H). 19F NMR (CDCl3, 282 MHz):
¼ꢁ61.68
d
(s, 3F). 13C NMR (100 MHz, CDCl3):
d
¼160.9, 159.0, 157.6, 153.2,
146.1,132.1 (q, 2JCF3¼40.8 Hz),129.8,120.3 (q, 1JCF3¼267.6 Hz),120.2,
3
117.9, 114.8, 109.1 (m, JCF3), 62.4, 62.3, 55.6, 14.1, 13.9. IR (KBr):
v¼2991, 1754, 1720, 1576, 1513, 1375, 1253, 1187, 1120, 1191, 1022,
840. MS: m/z (%)¼426 (Mþ, 100), 427 (23), 411 (21), 357 (42), 230
(230), 158 (21), 92 (28), 77 (38). HRMS (EI) calcd for C19H17F3N2O6:
426.1039; found: 426.1041.
4.4.11. Dimethyl 1-(4-bromophenyl)-3-(trifluoromethyl)-1H-furo[2,3-
c]pyrazole-4,5-dicarboxylate (4fa).
White solid; mp: 121e122 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼8.45 (d, J¼9.0 Hz, 2H), 8.16 (d, J¼9.0 Hz, 2H), 4.43e4.52 (m, 4H),
1.40e1.46 (m, 6H). 19F NMR (CDCl3, 282 MHz):
d
¼ꢁ62.21 (s, 3F).
13C NMR (100 MHz, CDCl3):
d
¼160.3, 157.2, 153.7, 147.0, 146.4,
2
1
140.7, 134.6 (q, JCF3¼40.8 Hz), 125.7, 119.8 (q, JCF3¼266.9 Hz),
118.5, 117.8, 110.2 (m, 3JCF3), 62.7, 14.1, 13.9. IR (KBr): v¼2994, 1746,
1573, 1532, 1482, 1343, 1284, 1144, 1088, 1055, 856, 749. MS: m/z
(%)¼441 (Mþ, 100), 368 (32), 245 (22), 173 (23), 141 (25), 127 (24),
76 (40), 75 (27). HRMS (EI) calcd for C18H14F3N3O7: 441.0784;
found: 441.0783.
4.4.9. Dimethyl
1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-furo
[2,3-c]pyrazole-4,5-dicarboxylate (4ea).
White solid; mp: 123e124 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼7.83 (d, J¼8.7 Hz, 2H), 7.67 (d, J¼8.7 Hz, 2H), 4.00 (s, 3H), 3.99
(s, 3H). 19F NMR (CDCl3, 282 MHz):
(100 MHz, CDCl3):
d
¼ꢁ62.26 (s, 3F). 13C NMR
d
¼160.8, 157.7, 153.3, 146.4, 135.4, 133.5
1
2
(q, JCF3¼41.5 Hz), 132.8, 121.1, 120.0 (q, JCF3¼268.3 Hz), 119.7,
3
116.0, 109.2 (m, JCF3), 53.0, 52.9. IR (KBr): v¼2956, 1727, 1593,
1573, 1479, 1430, 1266, 1164, 1092, 1035,825,739. MS: m/z (%)¼
446 (Mþ, 56), 448 (53), 367 (100), 266 (61), 264 (58), 157 (48), 155
(45), 75 (44). HRMS (EI) calcd for C16H10BrF3N2O5: 445.9725;
found: 445.0729.

Z. Zhang et al. / Tetrahedron 68 (2012) 5969e5978
5977
2
4.4.12. Diethyl 1-(4-bromophenyl)-3-(trifluoromethyl)-1H-furo[2,3-
c]pyrazole-4,5-dicarboxylate (4fb).
d
¼160.6, 157.4, 153.4, 146.6, 137.3, 135.8, 133.2 (q, JCF3¼40.1 Hz),
1
130.9, 127.8, 120.0 (q, JCF3¼267.6 Hz), 118.7, 117.8, 116.3, 109.6
3
(m, JCF3), 62.5, 62.4, 14.1, 13.9. IR (KBr): v¼1732, 1597, 1574, 1474,
1441, 1306, 1264, 1180, 1164, 1113, 1060, 773, 755. MS: m/z (%)¼
430 (Mþ, 89), 432 (30), 395 (100), 361 (36), 234 (28), 162 (35), 111
(88), 75 (35). HRMS (EI) calcd for C18H14ClF3N2O5: 430.0543;
found: 430.0542.
4.4.15. Dimethyl 1-(2,4-dichlorophenyl)-3-(trifluoromethyl)-1H-furo
[2,3-c]pyrazole-4,5-dicarboxylate (4ha).
White solid; mp: 98e99 ꢀC. 1H NMR (300 MHz, CDCl3):
(d, J¼8.7 Hz, 2H), 7.68 (d, J¼9.3 Hz, 2H), 4.42e4.49 (m, 4H),
d
¼7.84
1.39e1.44 (m, 6H). 19F NMR (CDCl3, 282 MHz):
d
¼ꢁ61.85 (s, 3F).
13C NMR (100 MHz, CDCl3):
d¼160.6, 157.4, 153.4, 146.6, 135.5,
2
1
133.5 (q, JCF3¼40.5 Hz), 133.3, 121.1, 120.0 (q, JCF3¼268.3 Hz),
119.8, 116.0, 109.6 (m, 3JCF3), 62.5, 62.4, 14.1, 13.9. IR (KBr): v¼2987,
1752, 1719, 1572, 1477, 1377, 1191, 1126, 1057, 850. MS: m/z (%)¼474
(Mþ, 74), 476 (69), 395 (100), 157 (53), 155 (58), 141 (32), 76 (41),
75 (34). HRMS (EI) calcd for C18H14BrF3N2O5: 474.0038; found:
474.0033.
White solid; mp: 132e133 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼7.98
(s, 1H), 7.85 (d, J¼8.1 Hz, 1H), 7.49 (t, J¼8.1 Hz, 1H), 7.37 (d, J¼8.1 Hz,
1H), 4.42e4.50 (m, 4H), 1.39e1.45 (m, 6H). 19F NMR (CDCl3,
¼ꢁ62.96 (s, 3F). 13C NMR (100 MHz, CDCl3):
¼160.9,
d
4.4.13. Dimethyl 1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-furo[2,3-
c]pyrazole-4,5-dicarboxylate (4ga).
282 MHz):
d
157.8, 154.9, 146.5, 137.0, 134.3 (q, 2JCF3¼40.8 Hz), 132.2, 131.1, 130.7,
129.1, 128.4, 119.9 (q, 1JCF3¼267.3 Hz), 118.6, 117.8, 108.6 (m, JCF3),
3
53.0. IR (KBr): v¼2959,1751,1725,1584,1475,1410,1354,1193,1163,
1128, 1059, 828, 964. MS: m/z (%)¼436 (Mþ, 30), 403 (19), 401 (51),
256 (37), 254 (56), 236 (22), 235 (100), 145 (21). HRMS (EI) calcd for
C16H9Cl2F3N2O5: 435.9841; found: 435.9837.
4.4.16. Diethyl 1-(2,4-dichlorophenyl)-3-(trifluoromethyl)-1H-furo
[2,3-c]pyrazole-4,5-dicarboxylate (4hb).
White solid; mp: 83e84 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼7.97 (s, 1H), 7.85 (d, J¼8.1 Hz, 1H), 7.49 (t, J¼8.1 Hz, 1H), 7.37
(d, J¼8.1 Hz, 1H), 4.01 (s, 3H), 3.99 (s, 3H). 19F NMR (CDCl3,
282 MHz):
d
d
¼ꢁ62.13 (s, 3F). 13C NMR (100 MHz, CDCl3):
2
¼160.8, 157.8, 153.4, 146.5, 137.2, 135.8, 133.3 (q, JCF3¼40.5 Hz),
1
130.9, 127.9, 120.0 (q, JCF3¼268.3 Hz), 118.6, 117.6, 116.2, 109.7
3
(m, JCF3), 53.0, 52.9. IR (KBr): v¼1749, 1735, 1596, 1574, 1443,
1359, 1181, 1159, 1114, 799, 756. MS: m/z (%)¼402 (Mþ, 65), 371
(23), 367 (88), 235 (32), 222 (36), 220 (100), 111 (55), 75 (34).
HRMS (EI) calcd for C16H10ClF3N2O5: 402.0230; found:
402.0028.
White solid; mp: 112e113 ꢀC. 1H NMR (300 MHz, CDCl3):
d¼7.98
(s, 1H), 7.85 (d, J¼8.1 Hz, 1H), 7.49 (t, J¼8.1 Hz, 1H), 7.37 (d, J¼8.1 Hz,
1H), 4.42e4.50 (m, 4H), 1.39e1.45 (m, 6H). 19F NMR (CDCl3,
282 MHz):
d
¼ꢁ62.96 (s, 3F). 13C NMR (100 MHz, CDCl3):
¼160.7,
d
4.4.14. Diethyl 1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-furo[2,3-
c]pyrazole-4,5-dicarboxylate (4gb).
157.4, 154.9, 146.6, 136.9, 134.2 (q, 2JCF3¼41.6 Hz), 132.2, 131.1, 130.7,
1
3
129.1, 128.4, 120.0 (q, JCF3¼267.6 Hz), 118.0, 108.5 (m, JCF3), 62.5,
62.4, 14.0, 13.9. IR (KBr): v¼2989, 1759, 1732, 1591, 1473, 1417, 1349,
1178, 1136, 1103, 857. MS: m/z (%)¼464 (Mþ, 58), 466 (42), 429
(100), 268 (33), 196 (43), 147 (34), 145 (61), 109 (34). HRMS (EI)
calcd for C18H13Cl2F3N2O5: 464.0154; found: 464.0150.
Acknowledgements
The authors thank the National Natural Science Foundation of
China (NNSFC) (Nos. 21032006 and 20972178).
White solid; mp: 94e95 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼7.98
References and notes
(s, 1H), 7.85 (d, J¼8.1 Hz, 1H), 7.49 (t, J¼8.1 Hz, 1H), 7.37
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New York, NY, 1978; 659.
(d, J¼8.1 Hz, 1H), 4.42e4.50 (m, 4H), 1.39e1.45 (m, 6H). 19F NMR
(CDCl3, 282 MHz):
d
¼ꢁ62.96 (s, 3F). 13C NMR (100 MHz, CDCl3):

5978
Z. Zhang et al. / Tetrahedron 68 (2012) 5969e5978
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