An efficient one-pot synthesis of aryl-substituted 1-(thiazol-2-yl)-1H- pyrazole-3-carboxylates via a hantzsch synthesis-knorr reaction sequence

Article abstract of DOI:10.1002/cjoc.201300878

The treatment of α-bromoalkyl aryl ketones and 2-(propan-2-ylidene) hydrazine carbothioamide afforded 4-aryl-2-(2-(propan-2-ylidene)hydrazinyl) thiazoles via a Hantzsch-thiazole synthesis, which reacted with 4-aryl-2,4-diketoesters via a sequential Knorr-

Full text of DOI:10.1002/cjoc.201300878

FULL PAPER
DOI: 10.1002/cjoc.201300878
An Efficient One-pot Synthesis of Aryl-substituted
1-(Thiazol-2-yl)-1H-pyrazole-3-carboxylates via a
Hantzsch Synthesis-Knorr Reaction Sequence
Chunhui Gu,a Jiaojiao Zhai,a Jianan Jiang,a Hongwei Liu,a
Lei Wang,b Dunru Zhu,*,b and Yafei Ji*,a
a School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
b State Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemistry and
Chemical Engineering, Nanjing University of Technology, Nanjing, Jiangsu 210009, China
The treatment of α-bromoalkyl aryl ketones and 2-(propan-2-ylidene)hydrazine carbothioamide afforded 4-aryl-
2-(2-(propan-2-ylidene)hydrazinyl)thiazoles via a Hantzsch-thiazole synthesis, which reacted with 4-aryl-2,4-di-
ketoesters via a sequential Knorr-pyrazole reaction to deliver a variety of aryl-substituted ethyl 1-(thiazol-2-yl)-1H-
pyrazole-3-carboxylates in a one-pot fashion with moderate to high yields. The key intermediates 4-aryl-2,4-diketo-
esters, existing as its enolic lithium salt, were synthesized in situ by a high-yield tert-BuOLi-mediated Claisen con-
densation of alkylphenones and diethyl oxalate. This class of elegant molecule comprises aryl groups on the two
different heterocyclic cores, and the configurations of two representative molecules were determined by single
crystal X-ray crystallography.
Keywords one-pot synthesis, Claisen condensation, Hantzsch synthesis, Knorr reaction, 1-(thiazol-2-yl)pyrazole-
3-carboxylates
Introduction
zole-3-carboxylate scaffold has been a focus in medici-
nal chemistry, in particular, it has served as cannabi-
noid-1 (CB1) receptor antagonists[10] (Figure 1b). The
synthesis of the promising drug scaffold with highly
structural diversity is greatly desirable for drug discov-
ery. As a part of our program aimed at constructing
functionalized pyrazoles[11a,11c] and thiazoles,[11b] we
attempted to synthesize new aryl-substituted 1-(thiazol-
2-yl)pyrazole-3-carboxylates in an efficient and step-
economical manner. Generally, novel and important
polyheterocyclic compounds would have enhanced bio-
logical activity or vagarious property. There are two
traditional methods to concisely create the 1-(thiazol-2-
yl)pyrazoles by means of hydrazine carbothioamide as
an initial molecular backbone (Scheme 1): (a) Knorr-
pyrazole reaction with 4-aryl-2,4-diketoesters, followed
by Hantzsch-thiazole synthesis using α-bromoalkyl aryl
ketones; (b) Hantzsch-thiazole synthesis of intermediate
B using α-bromoalkyl aryl ketones, followed by Knorr-
pyrazole reaction with 4-aryl-2,4-diketoesters. Herein,
we reported an efficient one-pot synthesis of ethyl 1-(4-
arylthiazol-2-yl)-5-aryl-1H-pyrazole-3-carboxylates (1)
in moderate to high yields via a Hantzsch synthesis-
Knorr reaction sequence, based on the recent work.[11]
Recently, a number of organic molecular architec-
tures comprising polyheterocyclic moieties have at-
tracted considerable attention due to their wide spec-
trum of biological activities.[1] Among polyhetero-
atomic rings, pyrazoles and thiazoles have exhibited a
great variety of biological properties and practical ap-
plications. Furthermore, the combination of the pyrazole
and thiazole into a N1,C2-tethered scaffold [referred to
as 1-(thiazol-2-yl)pyrazole] imparts distinct and inter-
esting structural characteristics with unique diheterocy-
cle’s functionality and more molecular diversity. Of the
1-(thiazol-2-yl)pyrazole compounds, a variety of bioac-
tivities such as analgesic,[2] anti-inflammatory,[3] anti-
bacterial,[4] antiviral[5] as well as inhibitors of Candida
elegans[6] and fibrinogen-mediated platelet aggregation[7]
(Figure 1a), have been revealed.
Although several investigations have assured a con-
tinuous attention on 1-(thiazol-2-yl)pyrazole deriva-
tives,[8] the approach to functionalized 1-(thiazol-
2-yl)pyrazole-3-carboxylates was still sparse. Con-
cretely speaking, the two reports relying on intermedi-
ates thiazol-2-ylhydrazonyl chlorides were inconvenient
and step-uneconomical.[9] On the other hand, the pyra-
*
E-mail: jyf@ecust.edu.cn, zhudr@njut.edu.cn; Tel./Fax: 0086-021-64253314
Received December 9, 2013; accepted January 19, 2014; published online February 17, 2014.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201300878 or from the author.
Chin. J. Chem. 2014, 32, 179—190
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179

Gu et al.
FULL PAPER
(a) representative bioactive 1-(thiazol-2-yl)pyrazoles
O
O
HO
N
N
S
N
N
N
S
N
O
S
N
H
O
N
N
Cl
N
N
Cl
antiviral[5]
antibacterial[4]
anti-inflammatory[3]
(b) pyrazole-3-carboxylate scaffold as CB1 receptor antagonists
Cl
Cl
Cl
Cl
Cl
N
N
N
NH
O
NH
N
N
NH
N
N
N
O
O
CN
CP-272871[10a]
O
Cl
I
Rimonabant[10b]
AM-251[10f]
Figure 1 Structure of 1-(thiazol-2-yl)pyrazoles and CB1 receptor antagonists.
Scheme 1 Two possible methods for the synthesis of aryl-sub-
stituted 1-(thiazol-2-yl)-1H-pyrazole-3-carboxylates (1, R1, R3＝
aryl)
order to prepare the pivotal ethyl 1-thiocar-bamoyl-5-
phenyl-1H-pyrazole-3-carboxylate (A', Scheme
2a).[10d,11c,12] However, the unexpected dethiocarbamoy-
lation overwhelmingly occurred, with ethyl 5-phenyl-
1H-pyrazole-3-carboxylate (4) as a major product in
87% yield. It was found that N1-thiocarbamoyl group is
susceptible to acidic reaction conditions giving rise to
an unusual dethiocarbamoylation. Any desired A' was
not observed indicating that the route was difficult to
pursue the set goal. Next, we turned our attention to the
reaction of α-bromoacetophenone (5a) with hydrazine
carbothioamide (Scheme 1b). Likewise, to our disap-
pointment, the dominant Hantzsch 1,3,4-thiadiazine
synthesis suppressed the desired Hantzsch-thiazole syn-
thesis leading to the undesired 6 in 78% yield, without
detectable target product 2-hydrazino-4-phenylthiazole
(B', Scheme 2b, see Supporting Information).[13]
(a)
O
O
OEt
COOEt
R2
R1
S
N
R2
O
NH2
N
H
H2N
N
S
R1
H2N
intermediate A
O
COOEt
R4
R3
R2
N
N
Br
S
R1
R4
N
R3
O
1
To avoid the unwanted 1,3,4-thiadiazines 6, an al-
ternative molecular backbone 2-(propan-2-ylidene)hy-
drazinecarbothioamide was employed to carry out the
desired Hantzsch-thiazole synthesis. Indeed, 5a
smoothly reacted in EtOH to accomplish the target thi-
azoles 7a in an excellent yield of 91%, fully excluding 6
(Scheme 2c). But, subsequent deisopropylidenation with
hydrazine hydrate only afforded B' in a low yield of
53%, as reported.[14] On the other hand, the desired ethyl
5-phenyl-1-(4-phenylthiazol-2-yl)-1H-pyrazole-3-carbox-
ylate (1aa) was achieved highly efficiently through a
hydrochloric acid-promoted Knorr-pyrazole reaction of
the resultant B' and the preprepared 3a in 94% yield.[11c]
Note that ketone exchange reactions of ketimines
with other ketones directly provided a new ketimines.[15]
Reasonably, we concluded that the desired 1aa might
also be afforded via reaction of ethyl 2,4-dioxo-4-
phenylbutanoate (free 3a) and 7a, with no need for an
additional deisopropylidenation (Scheme 2c). As ex-
pected, the treatment of 3a and 7a, under the mediation
of hydrochloric acid, efficiently achieved 1aa in an ex-
cellent yield of 93%. To clarify the selectivity of the
(b)
R4
NHNH2
N
R3
S
S
NH2
Br
H2N
N
H
R4
R3
B
intermediate
O
O
COOEt
N
OEt
R1
O
R2
R2
N
S
R4
R1
N
R3
Results and Discussion
Firstly, following the route of Scheme 1a, the enolic
lithium salt of ethyl 2,4-dioxo-4-phenylbutanoate (3a),
freshly prepared via tert-BuOLi-mediated Claisen con-
densation of acetophenone (2a) and diethyl oxalate in
THF,[11a] was added to an EtOH solution of hydrazine-
carbothioamide and concentrated hydrochloric acid in
180
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An Efficient One-pot Synthesis of Aryl-substituted 1-(Thiazol-2-yl)-1H-pyrazole-3-carboxylates
Scheme 2 Tentative approaches for the target product 1aa
(a) unsuccessful attempt
O
S
Li+
O-
S
N
HN
N
H2N
EtO
O
NH2
O
COOEt
N
OEt
CO2Et
H2N
N
+
OEt
H
O
Conc. HCl
EtOH, reflux, 8 h
t-BuOLi,
THF, r.t., 4 h
O
4 (87%)
2a
A' (0%)
3a
(b) unsuccessful attempt
S
N
NH2
S
N
N
NH2
O
NH2
H2N
Br
N
N
S
H
H
+
EtOH, r.t., 4 h
B'
6 (78%)
(0%)
5a
S
NHNH2
N
(c) discrete steps
O
S
N
B'
N
S
NH
H2N
N
H
Br
N
Conc. HCl
EtOH, reflux, 8 h
94%
EtOH, 40 oC, 4 h
91%
3a
5a
7a
CO2Et
N
S
N
N
1aa
(d) one-pot procedure
O
2a
diethyl oxalate
t-BuOLi,
THF, r.t., 4 h
CO2Et
S
N
N
N
S
O
H2N
N
Br
H
3a
N
7a
EtOH, 40 oC, 4 h
Conc. HCl
EtOH-THF,
reflux, 10 h
5a
1aa
(87%)
reaction, the NMR-based structure of 1aa was further
determined by single crystal X-ray crystallography
(Figure 2). The acquired results unambiguously con-
firmed its 1-(thiazol-2-yl)pyrazole-3-carboxylate motif
as a result of the regioselective Knorr reaction (Figure
S1, see Supporting Information). Additionally, the iso-
meric 1-(thiazol-2-yl)-1H-pyrazole-5-carboxylate prod-
uct was undetected in the reaction.[16]
It was noticed that, THF, used in the Claisen con-
densation, was well compatible with EtOH, used in
Hantzsch synthesis and Knorr reaction.[17] Besides, the
acidic conditions were uniformly required for the for-
mation of the thiazole and pyrazole rings. Naturally, we
attempted to assemble the discrete reaction steps into a
one-pot procedure. To our delight, the reaction of 5a
with 2-(propan-2-ylidene)hydrazinecarbothioamide was
conducted in EtOH at 40 ℃ for 4 h, followed by a di-
rect cyclization with freshly prepared 3a (unseparated),
Figure 2 Single crystal structure of 1aa.
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181

Gu et al.
FULL PAPER
under the mediation of hydrochloric acid and reflux for
a prolonged time of 10 h, to ultimately deliver the de-
sired 1aa in a yield of 87%. The combination of sequen-
tial Hantzsch synthesis and Knorr reaction, wherein
making use of the unseparated 3a arisen from the
Claisen condensation, virtually attained a step-, energy-,
separation- and purification-economical one-pot proce-
dure with a higher combined yield, in comparison with
the discrete steps (Scheme 2d).
With the convenient one-pot procedure in hand, the
scope of the substrates alkylphenones (2) and α-bromo-
alkyl aryl ketones (5) was evaluated to identify the fea-
sibility of the procedure for synthesis of 1 (Table 1).
Firstly, alkylphenones 2b－2i containing different R1
and R2 were assessed based on α-bromoacetophenone
(5a) (Entries 1－8). Compared to unsubstituted aceto-
phenone (2a, R1＝C6H5, R2＝H; Scheme 2d), as for the
acetophenones 2b and 2c, the procedure delivered the
desired products 1ba and 1ca in slightly low yields of
83% and 81%, respectively (Entries 1 and 2). The re-
sults indicated that the steric hindrance of substituent(s),
particularly an ortho-substituent at benzene ring, ex-
pressed an impact on the Claisen condensation and
Knorr reaction. Next, the products 1da－1fa were ob-
tained in lower yields of 72%－75% from propiophe-
nones 2d－2f, showing that the steric hindrance of R2
(R2＝CH3) possessed a striking impact on the efficacy
of the procedure (Entries 3－5). Furthermore, when R2
was designated as larger substituents (R2＝C2H5, C6H5),
the yields of the products 1ga and 1ha sharply reduced
to 68% and 60%, respectively (Entries 6 and 7), com-
paring with the yield of 1aa (Scheme 2d). In contrast,
the steric effect was not observed in a rigid cycloke-
tones 1-tetralone (2i), and the procedure offered the
corresponding product 1ia in a high yield of 85% (Entry
8).
Afterwards, α-bromoalkyl aryl ketones 5b－5h con-
taining different R3 and R4 were evaluated based on
acetophenone (2a) (Entries 9－15). As for
α-bromo-substituted acetophenones 5b (R3＝4-ClC6H4,
R4＝H) and 5c (R3＝3,4-O(CH2)3OC6H3, R4＝H), the
procedure efficiently afforded the corresponding prod-
Table 1 One-pot synthesis of aryl-substituted 1-(thiazol-2-yl)-1H-pyrazole-3-carboxylatesa
O
O
R2
OEt
R1
EtO
+
2
O
t-BuOLi
THF, 4 h
Li+
O
O-
S
R1
CO2Et
R4
R3
N
O
R2
S
CO2Et
R2
H2N
N
R4
R3
N
R4
H
S
N
3
N
R3
N
N
Conc. HCl
EtOH-THF, reflux, 10 h
H
N
EtOH, 40oC, 4 h
Br
R1
5
7
1
Entry
1
Yieldb/%
2
5
1
S
O
O
N
N
N
Br
CO2Et
83
81
75
Cl
5a
2b
Cl
1ba
S
Cl
O
N
N
N
CO2Et
2
3
5a
Cl
Cl
2c
Cl
1ca
S
O
N
N
N
CO2Et
5a
2d
1da
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An Efficient One-pot Synthesis of Aryl-substituted 1-(Thiazol-2-yl)-1H-pyrazole-3-carboxylates
Continued
Yieldb/%
Entry
2
5
1
S
O
N
N
N
CO2Et
4
5
6
73
72
68
5a
Cl
2e
Cl
1ea
S
Cl
O
N
N
N
CO2Et
5a
5a
Cl
2f
Cl
Cl
1fa
S
O
N
N
N
CO2Et
2g
1ga
S
N
N
O
N
CO2Et
7
60
5a
5a
2h
1ha
S
O
N
N
N
CO2Et
8
9
85
86
2i
1ia
S
Cl
O
O
N
N
N
Br
CO2Et
Cl
5b
2a
1ab
O
O
S
O
O
Br
N
N
N
10
83
2a
CO2Et
O
5c
1ac
S
O
N
N
Br
N
CO2Et
11
78
2a
5d
1ad
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Gu et al.
FULL PAPER
Continued
Yieldb/%
Entry
2
5
1
S
Cl
O
N
N
Br
N
CO2Et
12
76
2a
Cl
5e
1ae
S
Cl
O
Cl
Br
N
N
N
CO2Et
13
14
15
16
17
72
82
84
82
80
2a
2a
2a
Cl
Cl
5f
1af
S
O
O
N
N
N
Br
O
CO2Et
5g
1ag
S
O
N
S
N
N
Br
S
CO2Et
5h
1ah
S
Cl
O
O
N
N
N
Br
CO2Et
Cl
Cl
5b
2b
Cl
1bb
S
Cl
Cl
O
N
N
N
Br
CO2Et
Cl
2b
Cl
5i
Cl
1bi
S
O
N
N
N
Br
CO2Et
18
74
2b
5d
Cl
1bd
S
N
Cl
O
N
N
CO2Et
19
72
5d
Cl
2c
Cl
Cl
1cd
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An Efficient One-pot Synthesis of Aryl-substituted 1-(Thiazol-2-yl)-1H-pyrazole-3-carboxylates
Continued
Yieldb/%
Entry
2
5
1
S
O
N
N
N
CO2Et
20
21
22
23
24
68
65
64
64
59
5d
2d
1dd
S
O
O
Cl
Cl
Cl
N
N
N
N
Br
N
CO2Et
Cl
Cl
5e
2e
Cl
1ee
Cl
S
Cl
O
N
Br
N
CO2Et
2e
Cl
5f
Cl
1ef
S
Cl
O
N
N
CO2Et
5e
Cl
2f
Cl
Cl
1fe
S
Cl
N
N
N
CO2Et
Cl
2f
5f
Cl
Cl
1ff
a For the pre-prepared 3 (unseparated, via Claisen condensation): alkylphenones (2, 5.0 mmol), diethyl oxalate (6.0 mmol, 0.88 g),
t-BuOLi (6.5 mmol, 0.52 g) in anhydrous THF (15mL), r.t., 4 h. The one-pot procedure: α-bromoalkyl aryl ketones (5, 5.0 mmol),
2-(propan-2-ylidene)hydrazinecarbothioamide (5.0 mmol, 0.66 g) in EtOH (15mL), 40 ℃, 4 h; followed by addition of the pre-prepared
3 and conc. HCl (12.5 mmol, 1.0 mL), reflux, 10 h. b Isolated yield.
ucts 1ab and 1ac in high yields of 86% and 83%, re-
spectively (Entries 9 and 10). However, with respect to
α-bromo-substituted propiophenones 5d－5f (R4＝CH3),
the desired products 1ad－1af were obtained in mark-
edly reduced yields of 72%－78% (Entries 11－13).
These results clearly demonstrated that a major steric
hindrance of R4 and minor hindrance of the substi-
tutent(s) at the benzene ring emerged in the Hantzsch-
thiazole synthesis. It was noteworthy that the α-bromo-
ethyl heteroaryl ketones 5g and 5h were smoothly sub-
jected to the procedure resulting in the elegant trihet-
erocyclic molecules 1ag and 1ah in high yields of 82%
and 84%, respectively (Entries 14 and 15).
To further explore the generality of this one-pot
procedure, more densely substituted 1-(thiazol-2-yl)-
pyrazole-3-carboxylates (1) were synthesized by exam-
ining both 5 and 2 (Entries 16－24). With regard to
α-bromo-substituted acetophenones 5b and 5i, the pro-
cedure still took effect well to afford the desired 1bb
and 1bi in good yields of 82% and 80%, respectively,
from the same substrate 2b (Entries 16 and 17), once
again suggesting the slight steric hindrance of the sub-
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185

Gu et al.
FULL PAPER
stitutent(s) at the benzene ring of R3. Next, when
α-bromo-substituted propiophenones 5d was used, ace-
tophenones 2b and 2c were converted to the corre-
sponding products 1bd and 1cd in significantly reduced
yields of 74% and 72%, respectively (Entries 18 and 19),
consistently indicating the major detrimental influence
of the R4. Moreover, with larger steric hindrance-con-
taining propiophenones (2d, 2e and 2f) and α-bromo-
substituted propiophenones (5d, 5e and 5f) being em-
ployed, the procedure provided fully substituted
1-(thiazol-2-yl)pyrazoles 1dd, 1ee, 1ef, 1fe and 1ff in
moderate yields of 59% －68% (Entries 20 －24),
wherein the drastically reduced yields should be attrib-
uted to the dual impacts of R2 and R4. These results also
clearly demonstrated that the one-pot procedure was
qualified for constituting more complex molecular ar-
chitecture of 1-(thiazol-2-yl)pyrazoles.
Finally, the geometrical configuration of a fully sub-
stituted product 1ee was also determined by single
crystal X-ray crystallography, and the asymmetrical unit
consists of two crystallographically independent mole-
cules of 1ee (Figure 3).[18] The crystal structure is fur-
ther stabilized by an intermolecular π…π interaction and
an intramolecular edge-to-face C－H…π interaction
(Figure S2, see Supporting Information).
Experimental
General information
Unless otherwise indicated, all reagents were ob-
tained from commercial sources and used as received
without further purification. All reactions were carried
out in oven-dried glassware and monitored by thin layer
chromatography (TLC, precoated silica gel plates con-
taining HF254). All solvents were only dried over 4 Å
molecular sieves. Melting points were determined using
an open capillaries and uncorrected. NMR spectra were
determined on Bruker AV400 in CDCl3 or DMSO-d6
1
with TMS as the internal standard for H NMR (400
MHz) and 13C NMR (100 MHz), respectively. HRMS
were carried out on a QSTAR Pulsar I LC/TOF MS
mass spectrometer and Micromass GCTTM gas chro-
matograph-mass spectrometer. Crystal data of 1aa and
1ee were collected on a Brüker Smart APEX II CCD
diffractometer with monochromated Mo Kα radiation
(λ＝0.71073 Å) at 293 K, and operating in the φ-ω scan
mode. The structures were solved by direct methods and
refined on F2 by full matrix least-squares methods using
SHELXTL.
Tentative approaches for the target product 1aa
The tentative approaches were carefully conducted
in Supporting Information with the detailed procedures
and data confirmation.
One-pot synthesis of ethyl 1-(thiazol-2-yl)-5-aryl-
1H-pyrazole-3-carboxylates
24 products of various aryl-substituted 1-(thiazol-2-
yl)-1H-pyrazole-3-carboxylates were further synthe-
sized in the yields of 59%－86% with the one-pot pro-
cedure.
Preparation of 3 via Claisen condensation
Figure 3 Single crystal structure of 1ee (Table 1, Entry 21).
Diethyl oxalate (6.0 mmol, 0.88 g) was added to a
solution of alkylphenones (2, 5.0 mmol) and tert-BuOLi
(6.5 mmol, 0.52 g) in anhydrous THF (15 mL), and the
resulting mixture was allowed to stir at room tempera-
ture for 4 h. Subsequently, the prepared solution of 3
was subjected to the one-pot synthesis as below.
Conclusions
In summary, an efficient one-pot synthesis of aryl-
substituted ethyl 1-(thiazol-2-yl)pyrazole-3-carboxylates
has been developed for the first time. We successfully
combined the Hantzsch-thiazole synthesis and Knorr-
pyrazole reaction into a one-pot procedure, by using the
preformed enolic lithium salt of 4-aryl-2,4-diketoesters
resulting from the Claisen condensation. The procedure
provides a general and practical method for the regiose-
lective construction of multi-substituted 1-(thiazol-2-yl)-
pyrazoles from readily available diethyl oxalate, alkyl-
phenones, 2-(propan-2-ylidene)hydrazinecarbothioam-
ide and α-bromoalkyl aryl ketones. In addition, the
geometrical configurations of two representative prod-
ucts were determined by the single crystal X-ray crys-
tallography. Considering availability of the feedstocks,
simplicity of the procedure, broad scope of the sub-
strates and importance of the products, the methodology
is expected to have synthetically potential applications
in medicinal chemistry.
One-pot synthesis of 1
2-(Propan-2-ylidene)hydrazinecarbothioamide
(5
mmol, 0.66 g) was added to a solution of α-bromoalkyl
aryl ketones (5, 5.0 mmol) in EtOH (15 mL), and the
mixture was stirred at 40 ℃ for 4 h. Then, the prepre-
pared solution of 3 and conc. HCl (12.5 mmol, 1.0 mL)
were added at room temperature to the reaction mixture,
and the resulting mixtures were refluxed for another 10
h. After completion of the reaction as monitored by
TLC, the reaction solution was concentrated in vacuo to
remove EtOH and THF affording a residue, to which
were added H2O (15 mL) and CH2Cl2 (15 mL). The or-
ganic layer was separated, and the aqueous layer was
extracted with CH2Cl2 (10 mL×2). Finally, the com-
bined organic phase was washed with brine (35 mL),
186
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© 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2014, 32, 179—190

An Efficient One-pot Synthesis of Aryl-substituted 1-(Thiazol-2-yl)-1H-pyrazole-3-carboxylates
dried over anhydrous sodium sulfate, and concentrated
to give a crude product, which was purified by column
chromatography (200－300 mesh silica gel, petroleum
ether/ethyl acetate, V∶ V＝2∶1) to give the corre-
sponding 1.
Ethyl 5-(2,4-dichlorophenyl)-4-methyl-1-(4-phenyl-
thiazol-2-yl)-1H-pyrazole-3-carboxylate (1fa): pale
1
yellow solid, 1.65 g (72%), m.p. 138－140 ℃; H
NMR (400 MHz, CDCl3) δ: 7.57 (d, J＝2.0 Hz, 1H),
7.43 (dd, J＝8.2, 2.0 Hz, 1H), 7.37－7.28 (m, 6H), 7.24
(s, 1H), 4.48 (q, J＝7.2 Hz, 2H), 2.20 (s, 3H), 1.47 (t,
J＝7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 162.2,
159.6, 152.2, 143.6, 138.5, 136.3, 136.1, 133.6, 132.9,
129.4, 128.7 (2C), 128.2, 128.1, 127.1, 125.7 (2C),
122.5, 110.0, 61.3, 14.4, 9.2; HRMS (ESI) m/z: [M＋H＋]
calcd for C22H18Cl2N3O2S 458.0497, found 458.0492.
Ethyl
5-phenyl-1-(4-phenylthiazol-2-yl)-1H-pyra-
zole-3-carboxylate (1aa): pale yellow solid, 1.76 g
(94%), m.p. 120－122 ℃; 1H NMR (400 MHz, CDCl3)
δ: 7.59－7.50 (m, 4H), 7.48－7.42 (m, 3H), 7.35－7.27
(m, 4H), 7.00 (s, 1H), 4.47 (q, J＝7.2 Hz, 2H), 1.45 (t,
J＝7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 161.7,
159.7, 152.4, 146.0, 145.6, 133.6, 129.8 (2C), 129.4,
129.2, 128.6 (2C), 128.3, 128.0 (2C), 125.9 (2C), 111.7,
111.4, 61.5, 14.4; HRMS (ESI) m/z: [M＋H＋] calcd for
C21H18N3O2S 376.1120, found 376.1111.
Ethyl
4-ethyl-5-phenyl-1-(4-phenylthiazol-2-yl)-
1H-pyrazole-3-carboxylate (1ga): pale yellow solid,
1
1.37 g (68%), m.p. 135—136 ℃; H NMR (400 MHz,
CDCl3) δ: 7.53－7.48 (m, 3H), 7.42－7.38 (m, 4H),
7.30－7.22 (m, 4H), 4.48 (q, J＝7.2 Hz, 2H), 2.67 (q,
J＝7.6 Hz, 2H), 1.46 (t, J＝7.2 Hz, 3H), 1.15 (t, J＝7.6
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 162.3, 159.8,
152.2, 143.2, 142.7, 133.7, 130.5 (2C), 129.6, 128.9,
128.5 (2C), 128.20 (2C), 128.15, 127.9, 125.8 (2C),
110.4, 61.2, 17.1, 15.6, 14.3; HRMS (ESI) m/z: [M＋H＋]
calcd for C23H22N3O2S 404.1433, found 404.1434.
Ethyl 5-(4-chlorophenyl)-1-(4-phenylthiazol-2-yl)-
1H-pyrazole-3-carboxylate (1ba): pale yellow solid,
1
1.70 g (83%), m.p. 122－123 ℃; H NMR (400 MHz,
CDCl3) δ: 7.53 (d, J＝7.2 Hz, 2H), 7.49 (d, J＝8.4 Hz,
2H), 7.43 (d, J＝8.4 Hz, 2H), 7.38－7.27 (m, 4H), 6.99
(s, 1H), 4.47 (q, J＝7.2 Hz, 2H), 1.44 (t, J＝7.2 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ: 161.5, 159.6, 152.4,
145.6, 144.6, 135.4, 133.5, 131.2 (2C), 128.7 (2C),
128.4, 128.2 (2C), 127.8, 125.8 (2C), 111.8, 111.3, 61.6,
14.3; HRMS (ESI) m/z: [M＋H＋] calcd for C21H17Cl-
N3O2S 410.0730, found 410.0729.
Ethyl
4,5-diphenyl-1-(4-phenylthiazol-2-yl)-1H-
pyrazole-3-carboxylate (1ha): pale yellow solid, 1.35 g
(60%), m.p. 181－183 ℃; 1H NMR (400 MHz, CDCl3)
δ: 7.50－7.47 (d, J＝6.8 Hz, 2H), 7.37－7.22 (m, 14H),
4.34 (q, J＝7.2 Hz, 2H), 1.27 (t, J＝7.2 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ: 161.9, 159.6, 152.4, 143.2,
143.1, 133.6, 130.9 (2C), 130.8, 130.5 (2C), 128.86,
128.40, 128.6 (2C), 128.3, 128.0 (2C), 127.7 (2C),
127.4, 126.2, 125.9 (2C), 111.1, 61.3, 14.1; HRMS (ESI)
m/z: [M＋H＋] calcd for C27H22N3O2S 452.1433, found
452.1430.
Ethyl 5-(2,4-dichlorophenyl)-1-(4-phenylthiazol-2-
yl)-1H-pyrazole-3-carboxylate (1ca): pale yellow solid,
1
1.80 g (81%), m.p. 134－135 ℃; H NMR (400 MHz,
CDCl3) δ: 7.54 (s, 1H), 7.42－7.35 (m, 4H), 7.33－7.27
(m, 4H), 7.00 (s, 1H), 4.48 (q, J＝7.2 Hz, 2H), 1.45 (t,
J＝7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 161.4,
159.3, 152.3, 145.6, 140.8, 136.2, 135.8, 133.5, 132.5,
129.3, 128.7 (2C), 128.5, 128.3, 127.0, 125.7 (2C),
112.6, 110.5, 61.6, 14.3; HRMS (ESI) m/z: [M＋H＋]
calcd for C21H16Cl2N3O2S 444.0340, found 444.0336.
Ethyl 4-methyl-5-phenyl-1-(4-phenylthiazol-2-yl)-
1H-pyrazole-3-carboxylate (1da): pale yellow solid,
Ethyl
1-(4-phenylthiazol-2-yl)-4,5-dihydro-1H-
benzo[g]indazole-3-carboxylate (1ia): pale yellow solid,
1
1.70 g (85%), m.p. 164－165 ℃; H NMR (400 MHz,
CDCl3) δ: 7.94 (d, J＝7.2 Hz, 1H), 7.86 (d, J＝7.2 Hz,
2H), 7.50 (s, 1H), 7.42 (t, J＝7.2 Hz, 2H), 7.35 (t, J＝
7.2 Hz, 2H), 7.29 (t, J＝7.2 Hz, 1H), 7.21 (t, J＝7.2 Hz,
1H), 4.47 (q, J＝7.2 Hz, 2H), 3.10－2.99 (m, 4H), 1.45
(t, J＝7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ:
162.2, 160.7, 152.5, 141.9, 141.4, 137.7, 133.8, 128.9
(3C), 128.5, 128.4, 126.2, 126.1 (2C), 125.8, 125.2,
124.3, 112.6, 61.3, 30.1, 20.1, 14.4; HRMS (ESI) m/z:
[M ＋H ＋] calcd for C23H20N3O2S 402.1276, found
402.1273.
1
1.46 g (75%), m.p. 143－144 ℃; H NMR (400 MHz,
CDCl3) δ: 7.51－7.46 (m, 3H), 7.46－7.39 (m, 4H),
7.31－7.23 (m, 4H), 4.47 (q, J＝7.2 Hz, 2H), 2.25 (s,
3H), 1.46 (t, J＝7.2 Hz, 3H ); 13C NMR (100 MHz,
CDCl3) δ: 162.5, 159.9, 152.2, 143.7, 143.0, 133.7,
130.6 (2C), 129.4, 128.9, 128.6 (2C), 128.2 (3C), 125.8
(2C), 121.4, 110.6, 61.2, 14.4, 9.5; HRMS (ESI) m/z:
[M ＋H ＋] calcd for C22H20N3O2S 390.1276, found
390.1280.
Ethyl 1-(4-(4-chlorophenyl)thiazol-2-yl)-5-phenyl-
1H-pyrazole-3-carboxylate (1ab): pale yellow solid,
Ethyl
5-(4-chlorophenyl)-4-methyl-1-(4-phenyl-
1
thiazol-2-yl)-1H-pyrazole-3-carboxylate (1ea): pale
1.76 g (86%), m.p. 124－125 ℃; H NMR (400 MHz,
1
yellow solid, 1.55 g (73%), m.p. 127—129 ℃; H
CDCl3) δ: 7.53－7.50 (m, 2H), 7.49－7.41 (m, 5H),
7.31 (s, 1H), 7.27 (d, J＝8.0 Hz, 2H), 6.99 (s, 1H), 4.47
(q, J＝7.2 Hz, 2H), 1.44 (t, J＝7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ: 161.6, 159.9, 151.2, 145.9, 145.6,
134.0, 132.1, 129.8 (2C), 129.3, 129.2, 128.8 (2C),
128.0 (2C), 127.1 (2C), 111.8, 111.6, 61.5, 14.3; HRMS
(ESI) m/z: [M＋H＋] calcd for C21H17ClN3O2S 410.0730,
found 410.0722.
NMR (400 MHz, CDCl3) δ: 7.52－7.43 (m, 4H), 7.40－
7.29 (m, 5H), 7.28 (s, 1H), 4.50 (q, J＝7.2 Hz, 2H),
2.27 (s, 3H), 1.48 (t, J＝7.2 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ: 162.3, 159.8, 152.2, 143.7, 141.7,
135.2, 133.6, 132.0 (2C), 128.7 (2C), 128.4 (2C), 128.3,
128.0, 125.8 (2C), 121.6, 110.4, 61.3, 14.4, 9.4; HRMS
(ESI) m/z: [M＋H＋] calcd for C22H19ClN3O2S 424.0887,
found 424.0890.
Ethyl 1-(4-(3,4-dihydro-2H-benzo[b]1,4-dioxepin-
Chin. J. Chem. 2014, 32, 179—190
© 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
187

Gu et al.
FULL PAPER
7-yl)thiazol-2-yl)-5-phenyl-1H-pyrazole-3-carboxylate
(1ac): pale yellow solid, 1.86 g (83%), m.p. 108－109
℃; 1H NMR (400 MHz, CDCl3) δ: 7.54—7.40 (m, 5H),
7.20 (s, 1H), 7.17 (d, J＝2.0 Hz, 1H), 7.09 (dd, J＝8.4,
2.0 Hz, 1H), 6.99 (s, 1H), 6.89 (d, J＝8.4 Hz, 1H), 4.46
(q, J＝7.2 Hz, 2H), 4.21 (t, J＝5.6 Hz, 4H), 2.19 (quint,
J＝5.6 Hz, 2H), 1.44 (t, J＝7.2 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ: 161.7, 159.5, 151.7, 151.4, 151.2,
146.0, 145.5, 129.8 (2C), 129.3 (2C), 129.2, 128.0 (2C),
121.7, 121.1, 119.2, 111.6, 110.6, 70.5 (2C), 61.5, 31.7,
14.4; HRMS (ESI) m/z: [M＋H＋] calcd for C24H22N3-
O4S 448.1331, found 448.1334.
1H-pyrazole-3-carboxylate (1ah): pale yellow solid,
1.60 g (84%), m.p. 104－105 ℃; H NMR (400 MHz,
1
CDCl3) δ: 7.56－7.53 (m, 2H), 7.47－7.43 (m, 3H),
7.21－7.15 (m, 3H), 6.99 (s, 1H), 6.97 (d, J＝4.0 Hz
1H), 4.47 (q, J＝7.2 Hz, 2H), 1.44 (t, J＝7.2 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ: 161.6, 159.8, 147.1,
146.1, 145.7, 137.7, 129.9 (2C), 129.3, 129.1, 128.0
(2C), 127.7, 125.6, 124.3, 111.8, 109.9, 61.6, 14.4;
HRMS (ESI) m/z: [M＋H＋] calcd for C19H16N3O2S2
382.0684, found 382.0682.
Ethyl
5-(4-chlorophenyl)-1-(4-(4-chlorophenyl)-
thiazol-2-yl)-1H-pyrazole-3-carboxylate (1bb): pale
1
Ethyl 1-(5-methyl-4-phenylthiazol-2-yl)-5-phenyl-
1H-pyrazole-3-carboxylate (1ad): pale yellow solid,
yellow solid, 1.82 g (82%), m.p. 162－163 ℃; H
NMR (400 MHz, CDCl3) δ: 7.47 (d, J＝8.4 Hz, 2H),
7.43 (dd, J＝8.4, 2.8 Hz, 4H), 7.31 (s, 1H), 7.30 (d, J＝
7.6 Hz, 2H), 6.98 (s, 1H), 4.46 (q, J＝7.2 Hz, 2H), 1.44
(t, J＝7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ:
161.4, 159.8, 151.2, 145.7, 144.6, 135.5, 134.2, 132.0,
131.2 (2C), 128.9 (2C), 128.2 (2C), 127.8, 127.0 (2C),
111.9, 111.5, 61.6, 14.3; HRMS (ESI) m/z: [M＋H＋]
calcd for C21H16Cl2N3O2S 444.0340, found 444.0349.
Ethyl 5-(4-chlorophenyl)-1-(4-(2,4-dichlorophenyl)-
thiazol-2-yl)-1H-pyrazole-3-carboxylate (1bi): pale
1
1.52 g (78%), m.p. 174－176 ℃; H NMR (400 MHz,
CDCl3) δ: 7.52－7.49 (m, 2H), 7.45－7.36 (m, 5H),
7.33 (t, J＝7.2 Hz, 2H), 7.28 (d, J＝7.2 Hz, 1H), 7.00 (s,
1H), 4.46 (q, J＝7.2 Hz, 2H), 2.58 (s, 3H), 1.44 (t, J＝
7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 161.8,
155.2, 147.9, 145.8, 145.4, 134.2, 129.6 (2C), 129.3,
129.1, 128.3 (2C), 128.2 (2C), 128.1 (2C), 128.1, 127.6,
111.2, 61.4, 14.4, 12.8; HRMS (ESI) m/z: [M＋ H＋]
calcd for C22H20N3O2S 390.1276, found 390.1274.
Ethyl 1-(4-(4-chlorophenyl)-5-methylthiazol-2-yl)-
5-phenyl-1H-pyrazole-3-carboxylate (1ae): pale yellow
1
yellow solid, 1.92 g (80%), m.p. 169－170 ℃; H
NMR (400 MHz, CDCl3) δ: 7.84 (s, 1H), 7.46－7.42 (m,
5H), 7.32 (d, J＝8.4 Hz, 1H), 7.19 (dd, J＝7.6, 1.6 Hz,
1H), 6.99 (s, 1H), 4.47 (q, J＝7.2 Hz, 2H), 1.44 (t, J＝
7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 161.4,
158.8, 147.8, 145.8, 144.6, 135.5, 134.2, 132.1, 132.0,
131.1 (2C), 130.4, 130.3, 128.4 (2C), 127.9, 127.3,
117.3, 112.0, 61.7, 14.3; HRMS (ESI) m/z: [M＋H＋]
calcd for C21H15Cl3N3O2S 477.9951, found 477.9954.
1
solid, 1.61 g (76%), m.p. 143－144 ℃; H NMR (400
MHz, CDCl3) δ: 7.50－7.39 (m, 5H), 7.32－7.27 (m,
4H), 6.99 (s, 1H), 4.46 (q, J＝7.2 Hz, 2H), 2.56 (s, 3H),
1.43 (t, J＝7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ:
161.7, 155.4, 146.5, 145.7, 145.4, 133.5, 132.7, 129.6
(2C), 129.3 (2C), 129.3, 129.1, 128.4 (2C), 128.2, 128.1
(2C), 111.3, 61.4, 14.3, 12.8; HRMS (ESI) m/z: [M＋
＋
H
] calcd for C22H19ClN3O2S 424.0887, found
424.0884.
Ethyl 1-(4-(2,4-dichlorophenyl)-5-methylthiazol-2-
Ethyl
5-(4-chlorophenyl)-1-(5-methyl-4-phenyl-
thiazol-2-yl)-1H-pyrazole-3-carboxylate (1bd): pale
yellow solid, 1.57 g (74%), m.p. 199－201 ℃; H
1
yl)-5-phenyl-1H-pyrazole-3-carboxylate (1af): pale
yellow solid, 1.65 g (72%), m.p. 138－140 ℃; H
NMR (400 MHz, CDCl3) δ: 7.45 (d, J＝8.8 Hz, 2H),
7.41－7.34 (m, 6H), 7.32－7.29 (m, 1H), 6.98 (s, 1H),
4.46 (q, J＝7.2 Hz, 2H), 2.59 (s, 3H), 1.43 (t, J＝7.2 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ: 161.6, 155.2,
147.8, 145.4, 144.5, 135.3, 134.1, 131.0 (2C), 128.4
(2C), 128.3 (2C), 128.1 (2C), 128.0, 127.8, 127.7, 111.4,
61.5, 14.3, 12.8; HRMS (ESI) m/z: [M＋H＋] calcd for
C22H19ClN3O2S 424.0887, found 424.0883.
1
NMR (400 MHz, CDCl3) δ: 7.45－7.42 (m, 3H), 7.39－
7.35 (m, 3H), 7.23 (dd, J＝8.4, 2.1 Hz, 1H), 7.11 (d,
J＝8.4 Hz, 1H), 7.00 (s, 1H), 4.45 (t, J＝7.2 Hz, 2H),
2.33 (s, 3H), 1.43 (t, J＝7.2 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ: 161.8, 155.7, 146.2, 145.6, 145.4,
135.0, 134.6, 132.6, 132.2, 131.5, 129.6, 129.2 (2C),
129.2, 128.7, 128.3 (2C), 126.9, 110.8, 61.4, 14.3, 12.3;
HRMS (ESI) m/z: [M＋H＋] calcd for C22H18Cl2N3O2S
458.0497, found 458.0495.
Ethyl 5-(2,4-dichlorophenyl)-1-(5-methyl-4-phenyl-
thiazol-2-yl)-1H-pyrazole-3-carboxylate (1cd): pale
1
yellow solid, 1.65 g (72%), m.p. 124－126 ℃; H
Ethyl
1-(4-(furan-2-yl)thiazol-2-yl)-5-phenyl-1H-
NMR (400 MHz, CDCl3) δ: 7.51 (s, 1H), 7.36 (s, 2H),
7.34－7.27 (m, 3H), 7.23 (d, J＝8.0 Hz, 2H), 6.96 (s,
1H), 4.45 (q, J＝7.2 Hz, 2H), 2.57 (s, 3H), 1.43 (t, J＝
7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 161.5,
155.1, 147.4, 145.3, 140.5, 136.0, 135.7, 134.3, 132.5,
129.3, 128.5, 128.3 (2C), 127.9 (2C), 127.6, 127.0,
pyrazole-3-carboxylate (1ag): pale yellow solid, 1.50 g
(82%), m.p. 120－121 ℃; 1H NMR (400 MHz, CDCl3)
δ: 7.52－7.40 (m, 5H), 7.37 (s, 1H), 7.24 (s, 1H), 6.99
(s, 1H), 6.38 (d, J＝3.2 Hz, 1H), 6.30 (d, J＝3.2 Hz,
1H), 4.46 (q, J＝7.2 Hz, 2H), 1.44 (t, J＝7.2 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ: 161.6, 160.1, 149.6,
146.1, 145.7, 144.1, 142.4, 129.8 (2C), 129.3, 129.1,
128.0 (2C), 111.7, 111.5, 110.4, 107.6, 61.6, 14.4;
HRMS (ESI) m/z: [M＋H＋] calcd for C19H16N3O3S
366.0912, found 366.0912.
126.9, 112.4, 61.5, 14.3, 12.8; HRMS (ESI) m/z: [M＋
＋
H
] calcd for C22H18Cl2N3O2S 458.0497, found
458.0495.
Ethyl
4-methyl-1-(5-methyl-4-phenylthiazol-2-
yl)-5-phenyl-1H-pyrazole-3-carboxylate (1dd): pale
1
Ethyl
5-phenyl-1-(4-(thiophen-2-yl)thiazol-2-yl)-
yellow solid, 1.37 g (68%), m.p. 116－118 ℃; H
188
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© 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2014, 32, 179—190

An Efficient One-pot Synthesis of Aryl-substituted 1-(Thiazol-2-yl)-1H-pyrazole-3-carboxylates
X-ray crystallography of 1aa and 1ee
NMR (400 MHz, CDCl3) δ: 7.47－7.45 (m, 3H), 7.40－
7.37 (m, 2H), 7.31－7.23 (m, 5H), 4.46 (q, J＝7.2 Hz,
2H), 2.54 (s, 3H), 2.26 (s, 3H), 1.45 (t, J＝7.2 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ: 162.6, 155.4, 147.5,
143.4, 142.8, 134.3, 130.5 (2C), 129.3, 128.8, 128.19
(2C), 128.16 (2C), 128.1 (2C), 127.5, 127.1, 121.0, 61.1,
14.4, 12.7, 9.5; HRMS (ESI) m/z: [M＋H＋] calcd for
C23H22N3O2S 404.1433, found 404.1434.
See Supporting Information.
Acknowledgement
The authors are grateful to the National Natural Sci-
ence Foundation of China (Nos. 21176074 and
21171093) for financial support.
Ethyl 5-(4-chlorophenyl)-1-(4-(4-chlorophenyl)-5-
methylthiazol-2-yl)-4-methyl-1H-pyrazole-3-carboxylate
(1ee): pale yellow solid, 1.54 g (65%); m.p. 155－156
References
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℃; H NMR (400 MHz, CDCl3) δ: 7.45 (d, J＝8.0 Hz,
2H), 7.33－7.29 (m, 4H), 7.22 (d, J＝8.4 Hz, 2H), 4.46
(q, J＝7.2 Hz, 2H), 2.54 (s, 3H), 2.23 (s, 3H), 1.45 (t,
J＝7.2 Hz, 3H); 13CNMR (100 MHz, CDCl3) δ: 162.4,
155.6, 146.3, 143.6, 141.5, 135.2, 133.5, 132.7, 131.9
(2C), 129.2 (2C), 128.50 (2C), 128.47 (2C), 127.9,
127.3, 121.4, 61.2, 14.4, 12.8, 9.4; HRMS (ESI) m/z:
[M＋H＋] calcd for C23H20Cl2N3O2S 472.0653, found
472.0654.
Ethyl 5-(4-chlorophenyl)-1-(4-(2,4-dichlorophenyl)-
5-methylthiazol-2-yl)-4-methyl-1H-pyrazole-3-carboxyl-
ate (1ef): pale yellow solid, 1.62 g (64%), m.p. 134－
135 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.42 (d, J＝1.6
Hz, 1H), 7.37 (d, J＝8.4 Hz, 2H), 7.27 (d, J＝8.4 Hz,
2H), 7.23 (dd, J＝8.0, 1.6 Hz, 1H), 7.03 (d, J＝8.4 Hz,
1H), 4.45 (q, J＝7.2 Hz, 2H), 2.30 (s, 3H), 2.25 (s, 3H),
1.44 (t, J＝7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ:
162.4, 155.8, 145.2, 143.6, 141.8, 135.1, 134.9, 134.5,
132.6, 131.8 (2C), 131.5, 131.3, 129.6, 128.5 (2C),
127.2, 126.9, 121.0, 61.2, 14.4, 12.3, 9.5; HRMS (ESI)
m/z: [M＋H＋] calcd for C23H19Cl3N3O2S 506.0264,
found 506.0264.
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Ethyl 1-(4-(4-chlorophenyl)-5-methylthiazol-2-yl)-
5-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carb-
oxylate (1fe): pale yellow solid, 1.62 g (64%), m.p.
174－176 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.54 (d,
J＝1.6 Hz, 1H), 7.39 (dd, J＝8.4, 1.6 Hz, 1H), 7.31－
7.27 (m, 3H), 7.15 (d, J＝8.4 Hz, 2H), 4.47 (q, J＝7.2
Hz, 2H), 2.54 (s, 3H), 2.18 (s, 3H), 1.46 (t, J＝7.2 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ: 162.2, 155.5,
146.1, 143.4, 138.2, 136.2, 136.0, 133.4, 132.9, 132.8,
129.3, 129.0 (2C), 128.4 (2C), 128.1, 127.1, 126.6.
122.4, 61.3, 14.4, 12.8, 9.2; HRMS (ESI) m/z: [M＋H＋]
calcd for C23H19Cl3N3O2S 506.0264, found 506.0264.
Ethyl 5-(2,4-dichlorophenyl)-1-(4-(2,4-dichloro-
phenyl)-5-methylthiazol-2-yl)-4-methyl-1H-pyrazole-3-
carboxylate (1ff): pale yellow solid, 1.60 g (59%), m.p.
1
146－148 ℃; H NMR (400 MHz, CDCl3) δ: 7.45 (s,
1H), 7.40 (d, J＝1.6 Hz, 1H), 7.32－7.26 (m, 2H), 7.21
(dd, J＝8.4, 1.6 Hz, 1H), 7.00 (d, J＝8.4 Hz, 1H), 4.46
(q, J＝7.4 Hz, 2H), 2.29 (s, 3H), 2.16 (s, 3H), 1.45 (t,
J＝7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 162.3,
156.0, 145.1, 143.4, 138.5, 136.0, 135.9, 134.8, 134.4,
133.1, 132.5, 131.6, 130.3, 129.6, 129.4, 127.3, 127.1,
126.8, 122.3, 61.2, 14.4, 12.4, 9.3; HRMS (ESI) m/z:
[M＋H＋] calcd for C23H18Cl4N3O2S 539.9874, found
539.9879.
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FULL PAPER
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[18] CCDC 970392 (1aa) and 970393 (1ee) contain the supplementary
crystallographic data for this paper. These data can be obtained free
of charge from The Cambridge Crystallographic Data Centre via
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190
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© 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2014, 32, 179—190