Synthesis of dialkyl 5-(aryl)-1-phenyl-1H-prazole-3,4-dicarboxylates via a one-pot and four-component reaction

Article abstract of DOI:10.1016/j.tet.2010.10.070

A number of new dialkyl 5-(aryl)-1-phenyl-1H-prazole-3,4-dicarboxylate derivatives have been prepared regiospecifically in moderate to good yield from the cyclocondensation reaction of dialkyl (E)-2-(dialkoxyphosphoryl)-3-(aroyl)- 2-butenedioate, derived

Full text of DOI:10.1016/j.tet.2010.10.070

Tetrahedron 66 (2010) 9835e9839
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Synthesis of dialkyl 5-(aryl)-1-phenyl-1H-prazole-3,4-dicarboxylates
via a one-pot and four-component reaction
,
a
b
Abdolali Alizadeh a , Tahereh Firuzyar , Log-Guan Zhu
*
a Department of Chemistry, Tarbiat Modares University, PO Box 14115-175, Tehran, Iran
b Department of Chemistry, Zhejiang University, Hangzhou 310027, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 16 July 2010
Received in revised form 6 October 2010
Accepted 25 October 2010
Available online 1 November 2010
A number of new dialkyl 5-(aryl)-1-phenyl-1H-prazole-3,4-dicarboxylate derivatives have been prepared
regiospecifically in moderate to good yield from the cyclocondensation reaction of dialkyl (E)-2-(dia-
lkoxyphosphoryl)-3-(aroyl)-2-butenedioate, derived from the reaction between trimethyl phosphite, an
acetylenic ester, and an aroyl chloride, with phenylhydrazine. The reaction is four-component and is
carried out under reflux conditions in dry toluene.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Trimethyl phosphite
Acetylenic ester
Aroyl chlorides
Phenylhydrazine
Pyrazole
Four-component reaction
O
1. Introduction
F3C
CH3
HN
N
Substituted pyrazoles are an important class of five-membered
heterocyclic compounds that find widespread use in the pharma-
ceutical and agrochemical industries.1 These heterocycles are
known to possess wide variety of biological activities including
herbicidal,2 antimicrobial,3 antibacterial,4 anti-inflammatory,5 in-
secticidal,6 analgesic,7 and antipyretic8 activities. Specifically the
1,3,5-tri- and 1,3,4,5-tetrasubstituted pyrazoles, which constitute
the key structural units of blockbuster drugs, such as, Celebrex 19
and Acomplia 210 are of interest to medicinal chemist (Scheme 1).
The first method of 1,3,5-trisubstituted pyrazoles synthesis goes
back to 19th century when Knorr employed 1,3-diketones and hy-
drazines as starting materials.11 Owing to the formation of two
product isomers from the reactions of hydrazines with un-
symmetrical dicarbonyl compounds and the difficulty in separation,
many efforts, such as replacing the dicarbonyl compounds with
olefinic or acetylenic ketones have been reported to develop the
N
N
N
N
Cl
Cl
SO2NH2
Cl
Acomplia 2
Celebrex 1
Scheme 1.
(aroyl)-2-butenedioate derivatives using the reaction of trialkyl
phosphite and an acetylenic ester with various aroyl chlorides via
one-pot MCRs (Scheme 2).14
CO2R1
regioselective synthesis of the pyrazole rings.12 However
a,b-un-
saturated ketones have been applied as building blocks for the
preparation of pyrazoles, vinylphosphonates are also important
synthetic intermediates13 in heterocycle synthesis.
Recently, our research group reported the diastereoselective
synthesis of a novel series of dialkyl (E)-2-(dialkoxyphosphoryl)-3-
R
O
P
Ar
toluene, reflux
8 h
O
O
O
(RO)3P
R
O
91-96%
Ar
Cl
R1O2C
CO2R1
CO2R1
4
6
5
3
Scheme 2. Synthesis of dialkyl (E)-2-(dialkoxyphosphoryl)-3-(aroyl)-2-butenedioate
derivatives.
* Corresponding author. Tel.: þ98 21 8800663; fax: þ98 21 88006544; e-mail
address: aalizadeh@modares.ac.ir (A. Alizadeh).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.10.070

9836
A. Alizadeh et al. / Tetrahedron 66 (2010) 9835e9839
2. Results and discussion
as described for 7a. The mass spectrum of 7a displayed molecular
ion peak at m/z 381. The IR spectrum of 7a exhibited absorption
bands due to the carbonyl group of esters at 1729, Ar group at 1598
and 1521, C]N group at 1557 cmꢀ1 and the absorption bands of the
In continuation of this research, we became interested in the
application of phenylhydrazine as the fourth component in a mul-
ticomponent reaction for the synthesis of dialkyl 5-(aryl)-1-phenyl-
1H-prazole-3,4-dicarboxylate 7. Our strategy to reach this goal is
outlined in Scheme 3. Reaction between trialkyl phosphite 3,
acetylenic ester 4, aroyl chlorides 5, and phenylhydrazine in tolu-
ene under thermal and one-pot conditions leads to the formation of
dialkyl 5-(aryl)-1-phenyl-1H-prazole-3,4-dicarboxylate 7 after 14 h
in 70e85% yields.
CeO stretching appeared at 1345, 1220, 1096, and 1074 cmꢀ1
.
The 1H NMR spectrum of 7a exhibited two sharp singlets readily
recognized as arising from methoxy groups (
d¼3.80 and 4.00 ppm).
The aryl moiety exhibited characteristic signals in the aromatic
region of the spectrum and 15 distinct signals in the 1H decoupled
13C NMR spectrum of 7a are in agreement with proposed structure.
The 1H and 13C NMR spectra of compound 7bef are similar to those
CO2R1
R1O2C
CO2R1
Ar
R
O
P
Ar
toluene, reflux
8 h
O
O
O
PhNHNH2
(RO)3P
R
O
N
91-96%
toluene, reflux, 6-8 h
N
Ar
CO2R1
Cl
R1O2C
CO2R1
Ph
70-85%
6
3
5
7
4
Scheme 3.
The diversity of the MCR with respect to the aroyl chloride
component was investigated and indicated in Table 1.
of 7a except for the alkoxy of the ester groups, and the aryl moiety,
which exhibit characteristic signals with appropriate chemical
shifts. Finally, the structure of 7, for example, 7c, was further con-
firmed by a single crystal X-ray diffraction analysis (Fig. 1).
The structures of compounds 7aef were deduced from their
elemental analysis, mass, IR and high field 1H and 13C NMR spectra
Table 1
Synthesis of dialkyl 5-(aryl)-1-phenyl-1H-prazole-3,4-dicarboxylate 7
CO2R'
R'O2C
CO2R'
Ar
O
O
toluene, reflux
14 h
(RO)3P
P
RCl
PhNHNH2
N
Ar
Cl
RO
H
70-85%
N
OR
3
CO2R'
4
Ph
7
5
Entry
Vinylphosphonate 6 as intermediate
Product 7
Yield %
O
O
O2N
O
O
Me
N
O
P
a
85
N
O
O
NO2
Me
O
MeO2C
O2N
CO2Me
O
O
O
O
Me
N
O
P
b
83
N
O
O
NO2
Me
O
EtO2C
Br
CO2Et
O
O
O
O
Me
Me
N
O
c
75
N
O
P
O
Br
O
MeO2C
CO2Me

A. Alizadeh et al. / Tetrahedron 66 (2010) 9835e9839
9837
Table 1 (continued )
Entry
Vinylphosphonate 6 as intermediate
Product 7
Yield %
O
O
Br
O
O
Me
N
O
P
d
73
N
O
O
Br
Me
O
EtO2C
CO2Et
O
O
Cl
O
O
Me
N
O
e
70
N
O
P
O
Cl
Me
O
MeO2C
Cl
CO2Me
O
O
O
O
Me
N
O
P
f
74
N
O
O
Cl
Me
O
EtO2C
CO2Et
and subsequent attack of the resulting zwitterion 8 to the aroyl
chloride 5 to yield ion pair 9. Then, attack of the chloride ion would
yield the vinylphosphonates 6 (Scheme 4). The reaction of vinyl-
phosphonate 6 with phenylhydrazine leads to formation of in-
termediate 10. Probably, the intermediate 10 undergoes cyclization
followed by removal of a H2O molecule to convert to Product 7.
R1O2C
CO2R1
Ar
R1O2C
(RO)3P
CO2R1
5
-RCl
3
RO
RO
P
R
4
+
O
O
Cl
8
9
R
O
P
Ar
O
O
R
O
NH2NHPh
R1O2C
CO2R1
6
Ph
N
Ph
N
Ar
Ar
OH
Ar
CO2R1
HN
R1O2C
PhHNHN
R1O2C
O
N
-H2O
R1O2C
CO2R1
CO2R1
Fig. 1. The molecular structure of compound 7c.
11
10
7
Scheme 4. Possible mechanism for the formation of products 7aef.
Although we have not established the mechanism of the re-
action between phosphites 3, acetylenic ester 4, and aroyl chloride
5 in the presence of phenylhydrazine in an experimental manner,
a possible explanation is proposed in Scheme 4. On the basis of the
well-established chemistry of acetylenic esters,15,16 it is reasonable
to assume that the functionalized pyrazole derivatives 7 apparently
result from initial addition of the phosphite to the acetylenic ester
3. Conclusion
In summary, we have demonstrated that the one-pot four-
component reaction between phosphites 3, acetylenic esters 4, and

9838
A. Alizadeh et al. / Tetrahedron 66 (2010) 9835e9839
aroyl chloride 5 in the presence of phenylhydrazine provides
a simple method for the preparation of dialkyl 5-(aryl)-1-phenyl-
1H-prazole-3,4-dicarboxylates 7 of potential synthetic and phar-
macological interest. Fairly high yields of the products without any
activation, the ready availability of the starting materials, the re-
action’s simplicity are the main advantages of this method.
(2ꢂCHmeta of Ph), 134.5 (C4 of pyrazole), 138.1 (CipsoeC), 142.4
(CipsoeN), 144.5 (CipsoeNO2), 148.2 (C3 of pyrazole), 161.8 (CO2Et),
162.3 (CO2Et). Anal. Calcd for C21H19N3O6 (409.40): C, 61.61; H,
4.68; N, 10.26. Found: C, 61.62; H, 4.62; N, 10.12.
4.2.3. Dimethyl 5-(4-bromophenyl)-1-phenyl-1H-prazole-3,4-dicar-
boxylate (7c). White crystals, 0.31 g, yield 75%, mp 151e153 ꢁC. IR
(KBr): 1748 (CO2Me), 1725 (CO2Me), 1597 and 1475 (Ar), 1538 (C]
N), 1250 and 1225 (CeO) cmꢀ1. MS (EI, 70 eV): m/z (%)¼416 (Mþþ1,
9), 415 (Mþ, 3), 381 (31), 350 (36), 304 (10), 257 (9), 236 (18), 149
(16), 137 (16), 111 (24), 97 (43), 81 (52), 69 (100), 57 (69), 43 (74). 1H
NMR (500.13 MHz, CDCl3): dH¼3.78 (3H, s, OMe), 3.98 (3H, s, OMe),
4. Experimental
4.1. General
Phosphites, dialkyl acetylenedicarboxylates, aroyl chloride,
and phenylhydrazine were obtained from Merck (Germany) and
Fluka (Switzerland) and were used without further purification.
Melting points were measured on an Electrothermal 9100 appa-
ratus. Mass spectra were recorded on a FINNIGAN-MAT 8430 mass
spectrometer operating at an ionization potential of 20 eV 1H and
13C NMR spectra were measured (in CDCl3) with a Bruker DRX-500
AVANCE spectrometer at 500 and 125 MHz, respectively. IR
spectra (KBr) were recorded on a Shimadzu IR-460 spectrometer
3
7.14 (2H, d, JHH¼8.5 Hz, 2CH of Ar), 7.21e7.23 (2H, m, 2CH of Ph),
3
3
7.33 (2H, d, JHH¼7.2 Hz, 2CHortho of Ph), 7.34 (1H, t, JHH¼6.1 Hz,
CHpara of Ph), 7.46 (2H, d, JHH¼8.5 Hz, 2CH of Ar). 13C NMR
3
(125.75 MHz, CDCl3): dC¼52.3 (MeO), 52.6 (MeO), 115.5 (C5 of pyr-
azole), 124.2 (CipsoeBr), 125.7 (2ꢂCHortho of Ph), 126.8 (C4 of pyr-
azole), 128.9 (CHpara of Ph), 129.2 (2CH of Ar), 131.7 (2ꢂCHmeta of
Ph), 131.7 (2ꢂCH of Ar), 138.4 (CipsoeC), 143.5 (CipsoeN), 143.8 (C3 of
pyrazole), 162.2 (CO2Me), 163.2 (CO2Me). Anal. Calcd for
C19H15BrN2O4 (415.24): C, 54.96; H, 3.64; N, 6.75. Found: C, 54.58;
H, 3.41; N, 6.71. Crystal data for 7c C19H15BrN2O4 (CCDC 778305):
(n
in cmꢀ1).
ꢀ
4.2. General synthesis procedure: (for example, 7a)
MW¼415.24, triclinic, space group Pꢀ1, a¼8.9430 (4) A, b¼10.6351
ꢀ
ꢀ
a
ꢀ
(4) A, c¼11.7088 (5) A,
¼63.9010 (10)
b
¼88.2710 (10), ¼67.5250
g
3
3
To a magnetically stirred solution of dimethyl acetylenedi-
carboxylate (0.14 g, 1 mmol) and p-nitrobenzoyl chloride (0.19 g,
1 mmol) in dry toluene (2 mL) was added dropwise a solution of
trimethyl phosphite (0.12 g, 1 mmol) in dry toluene (3 mL) at room
temperature for 10 min. The reaction mixture was then allowed to
stir for 8 h at reflux. Finally a solution of phenylhydrazine (0.11 g,
1 mmol) in dry toluene (3 mL) was added and allowed to stir for 6 h
at reflux. Solvent was removed under reduced pressure, and the
residue was separated by silica gel (Merck 230e240 mesh) column
chromatography using hexaneeethyl acetate mixture as eluent.
(10), V¼911.24 (7) A , Z¼2, Dc¼1.513 mg/m , F (000)¼420, crystal
ꢀ
dimension 0.51ꢂ0.18ꢂ0.15 mm, radiation, Mo K
2.75ꢃ2 ꢃ27.22, intensity data were collected at 295 (2) K with
a Bruker APEX area-detector diffractometer, and employing /2
a
(
l
¼0.71073 A),
q
u
q
scanning technique, in the range of ꢀ10ꢃhꢃ10, ꢀ12ꢃkꢃ12,
ꢀ14ꢃlꢃ14; the structure was solved by a direct method, all non-
hydrogen atoms were positioned and anisotropic thermal param-
eters refined from 2835 observed reflections with R (into)¼0.0377
by a full-matrix least-squares technique converged to R¼0.0313
and Raw¼0.0902 [I>2
s(I)].
4.2.1. Dimethyl 5-(4-nitrophenyl)-1-phenyl-1H-prazole-3,4-dicarbox-
ylate (7a). White crystals, 0.32 g, yield 85%, mp 132e134 ꢁC. IR (KBr):
1729 (CO2Me),1598 and 1521 (Ar),1557 (C]N),1345,1220,1096, and
1074 (CeO) cmꢀ1. MS (EI, 70 eV): m/z (%)¼382 (Mþþ1, 19), 381 (Mþ,
83), 364 (15), 350 (100), 304 (25), 265 (11), 139 (20), 111 (19), 84 (46),
69 (39), 43 (28). 1H NMR (500.13 MHz, CDCl3): dH¼3.80 (3H, s, OMe),
4.00 (3H, s, OMe), 7.22 (2H, d, 3JHH¼7.1 Hz, 2CHortho of Ph), 7.36 (2H,
d, 3JHH¼7.4 Hz, 2CHmeta of Ph), 7.38 (1H, t, 3JHH¼6.5 Hz, CHpara of Ph),
7.47 (2H, d, 3JHH¼8.8 Hz, 2CH of Ar), 8.20 (2H, d, 3JHH¼8.7 Hz, 2CH of
Ar). 13C NMR (125.75 MHz, CDCl3): dC¼52.4 (MeO), 52.77 (MeO),
116.0 (C5 of pyrazole), 123.5 (2ꢂCH of Ar), 125.7 (2ꢂCHortho of Ph),
129.3 (CHpara of Ph),129.4 (2ꢂCH of Ar),131.3 (2ꢂCHmeta of Ph),134.3
(C4 of pyrazole), 138.0 (CipsoeC), 142.61 (CipsoeN), 143.9 (CipsoeNO2),
148.3 (C3 of pyrazole), 162.0 (CO2Me), 162.8 (CO2Me). Anal. Calcd for
C19H15N3O6 (381.34): C, 59.84; H, 3.96; N, 11.02. Found: C, 59.81; H,
3.93; N, 10.98.
4.2.4. Diethyl 5-(4-bromophenyl)-1-phenyl-1H-prazole-3,4-dicarbox-
ylate (7d). White crystals, 0.32 g, yield 73%, mp 161e163 ꢁC. IR
(KBr): 1734 (CO2Et), 1713 (CO2Et), 1594 and 1489 (Ar), 1532 (C]N),
1312, 1251, 1203 and 1067 (CeO) cmꢀ1. MS (EI, 70 eV): m/z (%)¼444
(Mþþ1, 61), 443 (Mþ, 16), 442 (62), 397 (58), 369 (44), 325 (13),
298 (40), 258 (43), 218 (18), 190 (10), 179 (10), 77 (100), 51 (20). 1H
NMR (500.13 MHz, CDCl3): dH¼1.23 (3H, t, 3JHH¼7.1 Hz, CH3CH2O),
1.42 (3H, t, 3JHH¼7.1 Hz, CH3CH2O), 4.25 (2H, q, 3JHH¼7.1, CH3CH2O),
4.46 (2H, q, 3JHH¼7.1 Hz, CH3CH2O), 7.15 (2H, d, 3JHH¼8.4 Hz, 2CH of
3
Ar), 7.22e7.24 (2H, m, 2CHmeta of Ph), 7.33 (2H, d, JHH¼6.8 Hz,
3
2CHortho of Ph), 7.34 (1H, t, JHH¼6.8 Hz, CHpara of Ph), 7.47 (2H, d,
3JHH¼8.3 Hz, 2CH of Ar). 13C NMR (125.75 MHz, CDCl3): dC¼13.9
(CH3CH2O), 14.2 (CH3CH2O), 61.2 (CH3CH2O), 61.8 (CH3CH2O), 115.5
(C5 of pyrazole), 124.1 (CipsoeBr), 125.7 (2ꢂCHortho of Ph), 127.0 (C4
of pyrazole), 128.7 (CHpara of Ph), 129.1 (2ꢂCH of Ar), 131.6
(2ꢂCHmeta of Ph), 131.7 (2CH of Ar), 138.5 (CipsoeC), 143.6 (CipsoeN),
144.1 (C3 of pyrazole), 162.0 (CO2Et), 162.7 (CO2Et). Anal. Calcd for
C21H19BrN2O4 (443.29): C, 56.90; H, 4.32; N, 6.32. Found: C, 56.69;
H, 4.29; N, 6.25.
4.2.2. Diethyl 5-(4-nitrophenyl)-1-phenyl-1H-prazole-3,4-dicarbox-
ylate (7b). White crystals, 0.34 g, yield 83%, mp 94e96 ꢁC. IR (KBr):
1743 (CO2Et), 1717 (CO2Et), 1580 and 1520 (Ar), 1547 (C]N), 1354
and 1218 (CeO) cmꢀ1. MS (EI, 70 eV): m/z (%)¼410 (Mþþ1, 23), 409
(Mþ, 100), 364 (65), 336 (94), 290 (22), 265 (70), 225 (50), 179 (61),
149 (26), 97 (22), 81 (35), 69 (65), 57 (43), 43 (49). 1H NMR
4.2.5. Dimethyl 5-(4-chlorophenyl)-1-phenyl-1H-prazole-3,4-dicar-
boxylate (7e). White crystals, 0.26 g, yield 70%, mp 131e134 ꢁC. IR
(KBr): 1746 (CO2Me), 1724 (CO2Me), 1599 and 1471 (Ar), 1537 (C]
N), 1258 and 1225 (CeO) cmꢀ1. MS (EI, 70 eV): m/z (%)¼372 (Mþþ1,
20), 371 (Mþ, 13), 370 (57), 339 (100), 214 (13), 77 (34). 1H NMR
3
(500.13 MHz, CDCl3): dH¼1.23 (3H, t, JHH¼7.1 Hz, CH3CH2O), 1.43
(3H, t, 3JHH¼7.1, CH3CH2O), 4.25 (2H, q, 3JHH¼7.1 Hz, CH3CH2O), 4.47
(2H, q, 3JHH¼7.1 Hz, CH3CH2O), 7.22 (2H, d, 3JHH¼6.9 Hz, 2CHortho of
Ph), 7.33e7.38 (3H, m, 3CH of Ph), 7.48 (2H, d, 3JHH¼8.6 Hz, 2CH of
(500.13 MHz, CDCl3): d ¼3.79 (3H, s, OMe), 3.99 (3H, s, OMe), 7.20
H
(2H, d, 3J¼8.4 Hz, 2CH of Ar), 7.31 (2H, d, 3J¼8.5 Hz, 2H, 2CH of Ar),
7.20e7.35 (m, 5H, 5CH of Ph). 13C NMR (125.75 MHz, CDCl3):
dC¼52.3 (OMe), 52.6 (OMe), 115.6 (C5 of pyrazole), 125.7 (2ꢂCHortho
of Ph), 126.3 (C4 of pyrazole), 128.8 (2ꢂCH of Ar), 128.9 (CHpara of
Ph), 129.2 (2ꢂCH of Ar), 131.5 (2ꢂCHmeta of Ph), 135.9 (CipsoeC),
3
Ar), 8.19 (2H, d, JHH¼8.6 Hz, 2CH of Ar). 13C NMR (125.75 MHz,
CDCl3): dC¼13.9 (CH3CH2O), 14.2 (CH3CH2O), 61.4 (CH3CH2O), 61.9
(CH3CH2O), 115.9 (C5 of pyrazole), 123.4 (2ꢂCH of Ar), 125.7
(2ꢂCHortho of Ph), 129.2 (CHpara of Ph), 129.3 (2ꢂCH of Ar), 131.4

A. Alizadeh et al. / Tetrahedron 66 (2010) 9835e9839
9839
138.4 (CipsoeBr), 143.5 (CipsoeN), 143.8 (C3 of pyrazole), 162.2
(CO2Me), 163.2 (CO2Me). Anal. Calcd for C19H15ClN2O4 (370.79): C,
61.55; H, 4.08; N, 7.56. Found: C, 60.53; H, 3.93; N, 7.57.
4. Tanitame, A.; Oyamada, Y.; Ofuji, K.; Fujimoto, M.; Suzuki, K.; Ueda, T.; Terauchi,
H.; Kawasaki, M.; Nagai, K.; Wachi, M.; Yamagishi, J.-I. Bioorg. Med. Chem. 2004,
12, 5515e5524.
5. (a) Sui, Z.; Guan, J.; Ferro, M. P.; McCoy, K.; Wachter, M. P.; Murray, W. V.; Singer,
M.; Steber, M.; Ritchie, D. M.; Argentieri, D. C. Bioorg. Med. Chem. Lett. 2000, 10,
601e604; (b) Bekhit, A. A.; Abdel-Aziem, T. Bioorg. Med. Chem. 2004, 12,
1935e1945; (c) Selvam, C.; Jachak, S. M.; Thilagavathi, R.; Chakraborti, A. K.
Bioorg. Med. Chem. Lett. 2005, 15, 1793e1797.
6. Katoch-Rouse, R.; Pavlova, L. A.; Caulder, T.; Hoffman, A. F.; Mukhin, A. G.; Horti,
A. G. J. Med. Chem. 2003, 46, 642e645.
7. Shchegol’kov, E. V.; Khudina, O. G.; Anikina, L. V.; Burgart, Y. V.; Saloutin, V. I.
Khim.-Farm. Zh. 2006, 40, 27e29.
8. Penning, T. D.; Talley, J. J.; Bertenshaw, S. R.; Carter, J. S.; Collins, P. W.; Docter, S.;
Graneto, M. J.; Lee, L. F.; Malecha, J. W.; Miyashiro, J. M.; Rogers, R. S.; Rogier, D.
J.; Yu, S. S.; Anderson, G. D.; Burton, E. G.; Cogburn, J. N.; Gregory, S. A.; Koboldt,
C. M.; Perkins, W. E.; Seibert, K.; Veenhuizen, A. W.; Zhang, Y. Y.; Isakson, P. C. J.
Med. Chem. 1997, 40, 1347e1365.
4.2.6. Diethyl
5-(4-chlorophenyl)-1-phenyl-1H-prazole-3,4-dicar-
boxylate (7f). White crystals, 0.29 g, yield 74%, mp 122e125 ꢁC. IR
(KBr): 1736 (CO2Et), 1716 (CO2Et), 1598 and 1491 (Ar), 1535 (C]N),
1314, 1251, 1203 and 1071 (CeO) cmꢀ1. MS (EI, 70 eV): m/z (%)¼400
(Mþþ1, 35), 399 (Mþ, 24), 398 (94), 381 (16), 353 (71), 325 (68), 281
(19), 254 (56), 214 (77), 199 (15), 111 (16), 77 (100), 69 (30), 43 (25).
3
1H NMR (500.13 MHz, CDCl3): dH¼1.23 (3H, t, JHH¼7.1, CH3CH2O),
1.43 (3H, t, 3JHH¼7.1, CH3CH2O), 4.25 (2H, q, 3JHH¼7.1 Hz, CH3CH2O),
3
4.47 (2H, q, JHH¼7.2 Hz, CH3CH2O), 7.20e7.34 (5H, m, 5CH of Ph),
7.21 (2H, d, 3JHH¼8.5 Hz, 2CH of Ar), 7.31 (2H, d, 3JHH¼8.4 Hz, 2CH of
Ar). 13C NMR (125.75 MHz, CDCl3): dC¼13.9 (CH3CH2O), 14.2
(CH3CH2O), 61.2 (CH3CH2O), 61.8 (CH3CH2O), 115.5 (C5 of pyrazole),
125.7 (2ꢂCH of Ar), 126.5 (C4 of pyrazole), 128.7 (2ꢂCH of Ar), 128.7
(CHpara of Ph), 129.1 (2ꢂCHortho of Ph), 131.5 (2ꢂCHmeta of Ph), 135.8
(CipsoeC), 138.5 (CipsoeBr), 143.6 (CipsoeN), 144.1 (C3 of pyrazole),
162.0 (CO2Et), 162.7 (CO2Et). Anal. Calcd for C21H19ClN2O4 (398.84):
C, 63.24; H, 4.80; N, 7.02. Found: C, 63.02; H, 4.56; N, 6.96.
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Supplementary data
Supplementary data associated with this article can be found in
online version at doi:10.1016/j.tet.2010.10.070. These data include
MOL files and InChIKeys of the most important compounds
described in this article.
References and notes
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