Meglumine catalyzed one-pot, three-component combinatorial synthesis of pyrazoles bearing a coumarin unit

Article abstract of DOI:10.1039/c5ra01677k

A simple, efficient, and eco-friendly procedure for the synthesis of a wide range of pyrazoles bearing a coumarin unit has been developed using a one-pot three-component reaction of salicylaldehyde, 4-hydroxy-6-methyl-2H-pyran-2-one, and hydrazine using m

Full text of DOI:10.1039/c5ra01677k

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• Graphical Abstract:
Meglumine catalyzed one-pot, three-component
combinatorial synthesis of pyrazoles bearing a
coumarin unit
Xiao-Tang Li, Yu-Heng Liu, Xin Liu, and Zhan-Hui
Zhang*
Meglumine has been found to be an efficient catalyst for the
synthesis of pyrazolylcoumarins by one-pot three-component
reaction of salicylaldehyde, 4-hydroxy-6-methyl-2H-pyran-2-one,
and hydrazine.

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Meglumine catalyzed one-pot, three-component combinatorial synthesis of
pyrazoles bearing a coumarin unit
XiaoꢀTang Lia, YuꢀHeng Liub, Xin Liua, ZhanꢀHui Zhanga,*
A simple, efficient, and ecoꢀfriendly procedure for synthesis of a wide range of pyrazoles bearing a
coumarin unit has been developed by oneꢀpot threeꢀcomponent reaction of salicylaldehyde,
4ꢀhydroxyꢀ6ꢀmethylꢀ2Hꢀpyranꢀ2ꢀone, and hydrazine using meglumine as a catalyst in aqueousꢀethanol
media. This new protocol offers several advantages including the use of biodegradable and inexpensive
catalyst, short reaction time, high yields, and simple workꢀup procedure.
Introduction
Currently, multicomponent reactions (MCRs) are becoming powerful and valuable synthetic strategy
in modern organic and medicinal chemistry because they make multistep synthesis to be conducted in a
single procedural step to provide novel and highly functionalized organic molecules and biologically active
heterocyclic compounds from simple and readily accessible starting materials. These reactions hold the
possibility for convenient, safe, atomꢀeconomic, highꢀyielding, and environmentally benign procedures and
reduce generation of chemical waste.1ꢀ4 On the other hand, catalysts based on biodegradable materials such
as chitosan,5 starch,6 cellulose,7 xanthan,8 polysaccharides,9 gluconic acid10 and eggshell11 have received
much attention. Meglumine is an amino sugar derived from sorbitol and can be widely used in
pharmaceuticals and medicine due to its peculiar physical and chemical properties such as low toxicity,
bioꢀcompatibility and bioꢀdegradability, low cost and nonꢀcorrosion nature. It was early reported by Gu as a
promoting medium with gluconic acid aqueous solution for hydroxymethylation of βꢀketosulfones with
formaldehyde.12 Meglumine contains amino group, primary and secondary hydroxyl groups. Therefore, it
can activate the reaction components by not only base centers but also hydrogen bonding. Recently, it has
been demonstrated that meglumine is a highly active catalyst for some organic transformations.13 Therefore,
the combination of MCRs and meglumine will make the chemical reaction more economical and
environmentally friendly.
_____________________________
aCollege of Chemistry & Material Science, Hebei Normal University, Shijiazhuang 050024, P. R. China. E-mail:
zhanhui@mail.nankai.edu.cn; zhanhui@mail.hebtu.edu.cn
bThe College of Preclinical Medicine, Hebei Medical University, Shijiazhuang 050017, China
1

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It is well known that pyrazole nucleus is an important core of various products and medicinal agents.
They exhibit broad spectra of biological activities such as anticancer,14 antibacterial,15 antitubercular,16
antimicrobial,17 antioxidant,18 and kinase inhibitors.19 In addition, coumarins represent another important
moiety occurring frequently in numerous natural products, pharmaceuticals, agrochemicals, dyes, and
functional materials.20 Due to the importance of these two structural frameworks, the development of a
simple procedure for the synthesis of aesthetically appealing molecular architecture containing both the
pyrazole moiety and coumarin framework using biodegradable material as a catalyst and green solvent is
still desirable and challenging task.
In view of the above points and as a continuation of our ongoing work on the development of
multicomponent reactions21 and environmentally friendly methodologies,22 attempts were made to
construct pyrazolylcoumarins via oneꢀpot, threeꢀcomponent coupling (TCC) reaction of salicylaldehyde,
4ꢀhydroxyꢀ6ꢀmethylꢀ2Hꢀpyranꢀ2ꢀone and hydrazine using meglumine as a biodegradable catalyst (Scheme
1).
Scheme 1 Oneꢀpot, threeꢀcomponent synthesis of pyrazolylcoumarins catalyzed by meglumine
Results and discussion
Initially, salicylaldehydes, 1,4ꢀhydroxyꢀ6ꢀmethylꢀ2Hꢀpyranꢀ2ꢀone and phenylhydrazine served as
model substrates for optimization of reaction conditions. Some of the key results are summarized in Table 1.
In the control experiments, no anticipated product was observed in the absence any catalyst (Table 1,
entries 1 and 2). Little product was obtained when the reaction was performed using Fe2O3 or Lꢀproline as
catalyst in a mixture of EtOH/H2O. When CaCO3, piperidine, 1,3ꢀdimethylurea, chitosan, betaine HCl,
mannitol, DMAP, Et3N or DABCO was employed as the catalyst, the reaction took place, however, the
yield of the target compound 4a was not satisfactory (entries 3ꢀ14). When the reaction was carried out in
deep eutectic solvents (DES) such as choline chloride: urea or citric acid: DMU, no improvement was
observed (entries 15 and 16). Further experiments found that meglumine was the best catalyst for this
threeꢀcomponent reaction and afforded the desired product 4a in an isolated yield of 80% within 1.5 h
(Table 1, entry 17).
2

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Subsequently, the reaction media, amounts of catalyst and reaction times were also examined. The
reaction did not proceed satisfactorily in water, possibly due to incomplete homogeneity of the reaction
mixture. Further studies showed that aqueousꢀethanol (1:1, v/v) was the best choice of solvent for this
transformation. The reaction was also carried out using different amounts of the catalyst and the results
showed that 20 mol% of catalyst was the best choice. Decreasing the amount of catalyst to 10 mol%
relative to substrate, the yield of product decreased (entry 25). When the reaction was conducted with
increasing amounts of meglumine or by prolonging the reaction times, the yield of 4a could not be further
increased. From the above investigations, the optimized reaction conditions were established by employing
salicylaldehyde, 4ꢀhydroxyꢀ6ꢀmethylꢀ2Hꢀpyranꢀ2ꢀone (1 mmol), and phenylhydrazine (1 mmol) with
meglumine (0.2 mmol) in aqueousꢀethanol (1:1 v/v, 4 ml) under reflux for 1.5 h (Table 1, entry 17).
Table 1 Optimization of the reaction conditions for the synthesis of 4a.a
Entry
1
Catalyst
Solvent
Temp (°C)
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
80
Time (min)
720
720
720
720
360
360
360
360
360
360
360
360
360
360
360
360
90
Yield (%)b
0
None
Ethanol
2
None
Ethanol: H2O (1: 1)
Ethanol: H2O (1: 1)
Ethanol: H2O (1: 1)
Ethanol: H2O (1: 1)
Ethanol: H2O (1: 1)
Ethanol: H2O (1: 1)
Ethanol: H2O (1: 1)
Ethanol: H2O (1: 1)
Ethanol: H2O (1: 1)
Ethanol: H2O (1: 1)
Ethanol: H2O (1: 1)
Ethanol: H2O (1: 1)
Ethanol: H2O (1: 1)
0
3
Fe2O3
Trace
Trace
20
4
LꢀProline
5
CaCO3
6
Piperidine
1,3ꢀDimethylurea
Chitosan
40
7
38
8
35
9
Betaine HCl
Mannitol
20
10
11
12
13
14
15
16
17
18
19
20
21
30
DMAP
42
DBU
60
Et3N
56
DABCO
68
Choline chloride: urea (1: 2)
Citric acid: DMU (40: 60)
Meglumine
Meglumine
Meglumine
Meglumine
Meglumine
42
80
30
Ethanol: H2O (1: 1)
H2O
Reflux
Reflux
Reflux
Reflux
Reflux
80
720
720
720
360
Trace
40
Glycerin
Glycerin: ethanol (1: 2)
Glycerin : H2O (1: 3)
48
56
3

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22
23
24
25
26
27
28
Meglumine
PEG400
CH3CN
Ethanol
100
360
360
90
45
36
70
65
60
80
80
80
Piperidine
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Meglumine
Meglumine (0.1 mmol)
Meglumine (0.4 mmol)
Meglumine (0.4 mmol)
Meglumine (0.4 mmol)
Meglumine (0.3 mmol)
Ethanol: H2O (1: 1)
Ethanol: H2O (1: 1)
Ethanol: H2O (1: 1)
Ethanol: H2O (1: 1)
Ethanol: H2O (1: 1)
90
60
90
360
90
29
a
Experimental conditions: salicylaldehyde (1 mmol), 4ꢀhydroxyꢀ6ꢀmethylꢀ2Hꢀpyranꢀ2ꢀone (1 mmol), phenylhydrazine (1 mmol), catalyst
(0.2 mmol), solvent (4 ml). b Isolated yield.
Under the optimized reaction conditions, the scope of this threeꢀcomponent reaction was considerably
expanded and the results are summarized in Figure 1. Various arylhydrazines bearing electronꢀdonating
group (EDG) and electronꢀwithdrawing group (EWG) underwent the reaction with salicylaldehydes and
4ꢀhydroxyꢀ6ꢀmethylꢀ2Hꢀpyranꢀ2ꢀone to afford the desired products in good to high yields. The influence of
substituents on the benzene ring of phenylhydrazine was also examined. In general, substituents possessing
an EDG tended to afford better yields than those bearing EWG. However, for phenylhydrazine with a
strong EWG such as (4ꢀnitrophenyl)hydrazine, no expected product was obtained. In addition to
arylhydrazines, we found that hydrazine was compatible and furnished the desired product 4g in good yield.
The 2ꢀhydrazinylpyridine worked well, providing high yield of expected 4h. Fortunately,
2ꢀhydrazinylbenzo[d]thiazole also proceeded efficiently, producing the corresponding product 4n in 70%
isolated yield.
Inspired by these encouraging results, we next explored the scope of this MCR process with respect to
salicylaldehydes. As anticipated, salicylaldehydes bearing either electronꢀdonating or electronꢀwithdrawing
groups such as hydroxyl, methoxy, NEt2, chloro, bromo and nitro were all tolerated and afforded the
respective products in good to high yields. Generally, the electronꢀwithdrawing substituted salicylaldehydes
showed better reactivity than the electronꢀdonating substituted salicylaldehydes. Furthermore,
2ꢀhydroxyꢀ1ꢀnaphthaldehyde participated in the reaction smoothly and delivered the products 4abꢀ4ae in
70ꢀ86% yield, respectively.
4

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O
O
N
O
O
N
O
O
N
O
O
N
O
O
N
N
N
N
N
N
F
OMe
F
4a 75%
80%
78%
76%
70%
O
O
O
O
N
O
O
MeO
O
O
MeO
O
O
N
N
N
HN
N
N
N
N
N
N
Br
72%
70%
77%
74%
MeO
70%
O
S
O
N
MeO
O
O
N
MeO
O
O
N
MeO
O
O
N
N
N
N
N
F
N
OH
F
Cl
74%
72%
70%
70%
O
O
N
HO
O
O
O
O
O
O
N
O2N
Cl
Cl
N
N
N
N
N
N
OMe
84%
72%
80%
85%
O
O
O
O
N
O
O
O
O
Cl
Cl
Cl
Cl
N
N
N
N
N
N
N
F
Br
F
71%
80%
86%
76%
O
O
N
O
O
O
O
N
O
O
Br
Cl
Br
Cl
N
Cl
N
N
N
N
HN
N
Cl
Cl
80%
89%
78%
85%
Cl
N
N
N
N
O
O
N
N
N
N
N
N
Cl
Br
O
O
O
Cl
O
N
O
O
O
O
OH
Cl
70%
70%
80%
86%
84%
Figure 1 Scope of pyrazolylcoumarin synthesis.
A proposed mechanism for the synthesis of 3ꢀ(3ꢀmethylꢀ1ꢀphenylꢀ1Hꢀpyrazolꢀ5ꢀyl)ꢀ2Hꢀchromenꢀ2ꢀone
(4a) from salicylaldehyde, 4ꢀhydroxyꢀ6ꢀmethylꢀ2Hꢀpyranꢀ2ꢀone, and phenylhydrazine catalyzed by
meglumine is shown in Scheme 2. We reasoned that in the presence of meglumine, Knoevenagel
5

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condensation of salicylaldehyde and 4ꢀhydroxyꢀ6ꢀmethylꢀ2Hꢀpyranꢀ2ꢀone would occur first to produce the
intermediate I. The intermediate I could then undergo intramolecular cyclization by the nucleophilic
addition of enolate oxygen to carbonyl group to afford the intermediate II. The intermediate II further
reacted with phenylhydrazine to form the intermediate IV, which then tautomerized to intermediate IV.
Finally, an intramolecular cyclization of intermediate IV promoted by meglumine would happen to give the
target product 4a by eliminating one molecule of water.
OH
H
O
O
O
OH
meglumine
O
Knoevenagel condensation
O
O
O
O
O
OH
I
2
Ph
H
H
N
O
O
HN
OH
N
H2N
Ph
O
O
O
O
III
II
Ph
HN
Ph
NH
O
NH
N
HO
tautomerization
4a
O
O
O
O
IV
V
Scheme 2. Plausible mechanism for synthesis of product 4a.
Conclusion
In summary, a novel, highly efficient and green procedure has been successfully developed for the
synthesis of a series of pyrazoles bearing a coumarin unit via oneꢀpot threeꢀcomponent reaction of
salicylaldehyde, 4ꢀhydroxyꢀ6ꢀmethylꢀ2Hꢀpyranꢀ2ꢀone, and hydrazine by using meglumine as an
inexpensive, biodegradable catalyst in aqueousꢀethanol media. Environmental acceptability, economic
viability, short reaction time, high yields, and cleaner reaction profiles are important features of this
protocol. This strategy opens a new opportunity for the preparation of libraries of a wide variety of
pyrazolylcoumarin derivatives for biological screening.
Experimental section
General information
All chemicals were purchased from commercial sources and used without further purification. Melting
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points were determined using an Xꢀ4 apparatus and are uncorrected. IR spectra were taken as KBr discs
1
with a Thermo Fisher Scientific Nicolet iS50 spectrometer. H and 13C NMR spectra were recorded on a
Bruker DRXꢀ500 spectrometer at 500 MHz and 125 MHz in CDCl3, respectively. Elemental analyses were
carried out on
a
Vario EL III CHNOS instrument. Mass spectra were recorded on a 3200
Qtrap instrument with an ESI source.
General procedure for the synthesis of pyrazolesubstituted derivatives
To a mixture of ethyl salicylaldehyde (1 mmol) and 4ꢀhydroxyꢀ6ꢀmethylꢀ2Hꢀpyranꢀ2ꢀone (1 mmol) in
ethanolꢀH2O (1:1) (4 mL) was added hydrazine (1 mmol), and meglumine (0.2 mmol) at room temperature.
The reaction mixture was stirred under reflux and monitored by TLC. After completion of the reaction, the
reaction mixture was cooled to room temperature. The solid product was separated, washed with ether and
purified by column chromatography on silica gel (eluent: EtOAc–hexane 1:9).
Characterization data
3-(3-Methyl-1-phenyl-1H-pyrazol-5-yl)-2H-chromen-2-one (4a). White solid, 130ꢀ131 °C (Lit.
1
126ꢀ127 °C)23; IR (KBr): 3032, 1780, 1680, 1620, 1500, 1465, 1386, 1012 cmꢀ1; H NMR (CDCl3, 500
MH ) δ ppm: 7.55ꢀ7.52 (m, 1H), 7.46 (s, 1H), 7.42ꢀ7.40 (m, 3H), 7.38 (s, 1H), 7.34ꢀ7.31 (m, 3H), 7.24 (d, J
Z
= 7.5 Hz, 1H), 6.61 (s, 1H), 2.40 (s, 3H); 13C NMR (125 MHz, CDCl3) δ ppm: 157.0, 155.1, 153.1, 143.1,
139.6, 129.6, 121.2, 118.8, 117.4, 116.6, 116.4, 114.7, 114.5, 112.7, 28.9; Anal. Calcd for C19H14N2O2: C,
75.48; H, 4.67; N, 9.27. Found: C, 75.65; H, 4.50; N, 9.44; ESIꢀMS: m/z = 303 (M+1)+.
3-(1-(2-Methoxyphenyl)-3-methyl-1H-pyrazol-5-yl)-2H-chromen-2-one (4b). White solid, 191ꢀ192 °C;
IR (KBr): 3015, 1738, 1661, 1613, 1516, 1453, 1389, 1163, 756, 693 cmꢀ1; 1H NMR (CDCl3, 500 MH
) δ
Z
ppm: 8.50 (s, 1H), 7.51 (d, J = 7.5 Hz, 2H), 7.48 (t, J = 5.5 Hz, 2H), 7.39 (d, J = 7.5 Hz, 2H), 7.35 (d, J =
8.0 Hz, 1H), 6.91 (s, 1H), 6.83 (s, 1H), 3.83 (s, 3H), 2.18 (s, 3H); 13C NMR (125 MHz, CDCl3) δ ppm:
160.1, 154.7, 148.8, 142.2, 136.3, 133.6, 131.0, 130.5, 129.5, 128.3, 127.9, 127.6, 126.9, 126.4, 125.8,
120.7, 117.3, 112.3, 29.7, 14.1; Anal. Calcd for C20H16N2O3: C, 72.28; H, 4.85; N, 8.43. Found: C, 72.45; H,
4.68; N, 8.60; ESIꢀMS: m/z = 333 (M+1)+.
3-(3-Methyl-1-(o-tolyl)-1H-pyrazol-5-yl)-2H-chromen-2-one (4c). White solid, 149ꢀ150 °C; IR (KBr):
3119, 1745, 1638, 1612, 1496, 1454, 1398, 1165, 750, 709 cmꢀ1; 1H NMR (CDCl3, 500 MH
(s, 1H), 7.52 (t, J = 7.0 Hz, 2H), 7.41 (t, J = 7.0 Hz, 1H), 7.38 (s, 1H), 7.37 (d, J = 5.0 Hz, 1H), 7.34 (d, J =
Z
) δ ppm: 8.50
7.5 Hz, 1H), 7.31 (d, J = 7.5 Hz, 1H), 7.28 (d, J = 7.5 Hz, 1H), 7.10 (s, 1H), 2.17 (s, 3H), 2.13 (s, 3H); 13
C
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NMR (125 MHz, CDCl3) δ ppm: 160.1, 153.4, 145.2, 140.9, 138.5, 137.3, 136.1, 131.1, 129.5, 128.9,
127.7, 126.7, 124.5, 120.7, 119.7, 116.4, 107.0, 17.3, 11.5; Anal. Calcd for C20H16N2O2: C, 75.93; H, 5.10; N,
8.86. Found: C, 76.10; H, 4.93; N, 9.03; ESIꢀMS: m/z = 317 (M+1)+.
3-(3-Methyl-1-(m-tolyl)-1H-pyrazol-5-yl)-2H-chromen-2-one (4d). White solid, 164 °C; IR (KBr):
1
3001, 1767, 1654, 1630, 1496, 1460, 1384, 1048 cmꢀ1; H NMR (CDCl3, 500 MH
Z) δ ppm: 8.51 (s, 1H),
7.55 (d, J = 7.5 Hz, 1H), 7.51 (t, J = 7.5 Hz, 1H), 7.40ꢀ7.35 (m, 2H), 7.34 (s, 1H), 7.28 (d, J = 7.5 Hz, 2H),
7.24 (d, J = 7.5 Hz, 1H), 7.06 (s, 1H), 2.44 (s, 3H), 2.37 (s, 3H); 13C NMR (125 MHz, CDCl3) δ ppm:
160.0, 153.4, 145.2, 140.1, 137.4, 131.2, 129.0, 128.9, 128.1, 125.9, 124.5, 122.1, 120.6, 119.6, 116.4,
108.3, 21.4, 12.5; Anal. Calcd for C20H16N2O2: C, 75.93; H, 5.10; N, 8.86. Found: C, 76.10; H, 4.93; N, 9.03;
ESIꢀMS: m/z = 317 (M+1)+.
3-(1-(3,4-Difluorophenyl)-3-methyl-1H-pyrazol-5-yl)-2H-chromen-2-one (4e).
1
White solid, 209ꢀ210 °C; IR (KBr): 3032, 1750, 1668, 1600, 1502, 1543, 1381, 1050, 700 cmꢀ1; H
NMR (CDCl3, 500 MH
Z
) δ ppm: 8.47 (s, 1H), 7.54 (d, J = 8.0 Hz, 1H), 7.51 (t, J = 8.0 Hz, 1H), 7.41 (t,J =
8.0 Hz, 1H), 7.35 (d, J = 8.0 Hz, 1H), 7.30ꢀ7.27 (m, 2H), 7.07 (s, 1H), 6.99ꢀ6.89 (m, 1H), 2.38 (s, 3H); 13
C
NMR (125 MHz, CDCl3) δ ppm: 159.9, 153.5, 150.2 (dd, JFC = 249.5, 13.6 Hz), 149.9 (dd, JFC = 248.9,
12.5 Hz), 145.9, 140.1, 137.8, 136.0 (dd, JFC = 8.0, 3.5 Hz), 131.4, 128.2, 124.6, 120.9 (dd, JFC = 6.4, 3.7
Hz), 120.2, 119.5, 117.6 (d, JFC = 18.5 Hz), 116.4, 114.7 (d, JFC = 19.6 Hz), 109.0, 12.5; Anal. Calcd for
C19H12F2N2O2: C, 67.45; H, 3.58; N, 8.28. Found: C, 67.62; H, 3.41; N, 8.45; ESIꢀMS: m/z = 339 (M+1)+.
3-(1-(4-Bromophenyl)-3-methyl-1H-pyrazol-5-yl)-2H-chromen-2-one (4f). White solid, 212ꢀ213 °C; IR
(KBr): 3013, 1724, 1661, 1611, 1494, 1454, 1340, 1070, 753, 690 cmꢀ1; 1H NMR (CDCl3, 500 MH
) δ ppm:
Z
8.51 (s, 1H), 7.66 (d, J = 8.5 Hz, 2H), 7.58 (d, J = 8.0 Hz, 1H), 7.54 (t, J = 8.0 Hz, 1H), 7.43 (d, J = 8.5 Hz,
2H), 7.39 (d, J = 8.0 Hz, 1H), 7.31 (t, J = 8.0 Hz, 1H), 7.11 (s, 1H), 2.41 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ ppm: 160.0, 153.5, 145.8, 140.1, 138.7, 137.7, 132.4, 131.3, 128.5, 128.2, 126.5, 126.2, 124.5,
121.8, 120.4, 119.6, 116.4, 108.9, 12.5; Anal. Calcd for C19H13BrN2O2: C, 59.86; H, 3.44; N, 7.35. Found: C,
60.03; H, 3.27; N, 7.52; ESIꢀMS: m/z = 381 (M+1)+.
3-(3-Methyl-1H-pyrazol-5-yl)-2H-chromen-2-one (4g). White solid, 180ꢀ181 °C (Lit. 182 °C)23; IR
1
(KBr): 3432, 2954, 1728, 1713, 1610, 1554, 1459, 1394, 1032 cmꢀ1; H NMR (CDCl3, 500 MH
Z) δ ppm:
8.03 (d, J = 7.5 Hz, 1H), 7.53 (d, J = 7.0 Hz, 1H), 7.43 (s, 1H), 7.03 (t, J = 8.5 Hz, 1H), 6.98 (d, J = 7.0 Hz,
1H), 6.91 (s, 1H), 2.27 (s, 3H); 13C NMR (125 MHz, CDCl3) δ ppm: 159.8, 150.9, 146.0, 135.5, 131.1,
127.8, 125.2, 123.4, 117.8, 114.4, 32.0; Anal. Calcd for C13H10N2O2: C, 69.02; H, 4.46; N, 12.38. Found: C,
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69.19; H, 4.29; N, 12.55; ESIꢀMS: m/z = 227 (M+1)+.
3-(3-Methyl-1-(pyridin-2-yl)-1H-pyrazol-5-yl)-2H-chromen-2-one (4h). White solid, 158ꢀ160 °C;
IR (KBr): 3018, 1735, 1640, 1600, 1593, 1475, 1384, 1054 cmꢀ1; 1H NMR (CDCl3, 500 MH
Z) δ ppm: 8.18
(d, J = 4.5 Hz, 1H), 7.94 (s, 1H), 7.65 (t, J = 7.0 Hz, 1H), 7.55ꢀ7.51 (m, 1H), 7.37ꢀ7.33 (m, 1H), 7.19 (d, J =
7.5 Hz, 1H), 7.08 (s, 1H), 7.00 (d, J = 8.0 Hz, 1H), 6.92 (t, J = 7.5 Hz, 1H), 6.84 (t, J = 6.0 Hz, 1H), 2.17 (s,
3H); 13C NMR (125 MHz, CDCl3) δ ppm: 157.2, 155.5, 147.8, 147.2, 142.9, 139.2, 138.6, 130.5, 129.8,
119.6, 118.2, 116.7, 116.4, 106.6, 30.9; Anal. Calcd for C18H13N3O2: C, 71.28; H, 4.32; N, 13.85. Found: C,
71.45; H, 4.15; N, 14.02; ESIꢀMS: m/z = 304 (M+1)+.
7-Methoxy-3-(3-methyl-1-phenyl-1H-pyrazol-5-yl)-2H-chromen-2-one (4i). Yellow oil; IR (KBr):
3047, 1726, 1604, 1503, 1458, 1383, 1074, 776, 695 cmꢀ1; 1H NMR (CDCl3, 500 MH
) δ ppm: 8.48 (s, 1H),
Z
7.75ꢀ7.73 (m, 1H), 7.56ꢀ7.54 (m, 1H), 7.54ꢀ7.53 (m, 3H), 7.48ꢀ7.44 (m, 2H), 7.06 (s, 1H), 6.89 (s, 1H),
3.91 (s, 3H), 2.40 (s, 3H); 13C NMR (125 MHz, CDCl3) δ ppm: 162.6, 155.3, 145.8, 140.0, 137.9, 132.3,
130.9, 129.2, 129.1, 128.8, 127.9, 125.1, 112.9, 108.2, 100.4, 65.6, 19.2; Anal. Calcd for C20H16N2O3: C,
72.28; H, 4.85; N, 8.43. Found: C, 72.45; H, 4.68; N, 8.60; ESIꢀMS: m/z = 333 (M+1)+.
6-Methoxy-3-(3-methyl-1-(o-tolyl)-1H-pyrazol-5-yl)-2H-chromen-2-one (4j). White solid, 148ꢀ150 °C;
IR (KBr): 3003, 1742, 1663, 1609, 1514, 1454, 1333, 1088, 778, 700 cmꢀ1; 1H NMR (CDCl3, 500 MH
) δ
Z
ppm: 8.09 (s, 1H), 7.71 (d, J = 9.0 Hz, 2H), 7.53 (d, J = 8.5 Hz, 1H), 7.48 (d, J = 7.5 Hz, 1H), 7.44 (d, J =
7.5 Hz, 1H), 7.17 (t, J = 7.0 Hz, 2H), 7.09 (s, 1H), 3.85 (s, 3H), 2.40 (s, 3H), 2.31 (s, 3H); 13C NMR (125
MHz, CDCl3) δ ppm: 161.7, 153.2, 151.9, 150.5, 149.6, 145.7, 140.0, 138.1, 137.1, 132.3, 131.6, 130.9,
128.8, 127.2, 126.2, 122.4, 117.7, 113.3, 29.7, 19.2, 13.7; Anal. Calcd for C21H18N2O3: C, 72.82; H, 5.24; N,
8.09. Found: C, 72.99; H, 5.07; N, 8.26; ESIꢀMS: m/z = 347 (M+1)+.
7-Methoxy-3-(3-methyl-1-(m-tolyl)-1H-pyrazol-5-yl)-2H-chromen-2-one (4k). White solid,
163ꢀ165 °C; IR (KBr): 3007, 1735, 1700, 1631, 1507, 1465, 1384, 1049, 728, 695 cmꢀ1; 1H NMR (CDCl3,
500 MH ) δ ppm: 7.61 (s, 1H), 7.58 (d, J = 8.5 Hz, 1H), 7.53ꢀ7.42 (m, 1H), 7.34 (t, J = 7.5 Hz, 1H), 7.30 (t,
Z
J = 6.5 Hz, 1H), 7.13 (d, J = 8.5 Hz, 1H), 7.08 (d, J = 7.5 Hz, 1H), 6.69 (d, J = 8.0 Hz, 1H), 6.65 (s, 1H),
3.81 (s, 3H), 2.43 (s, 3H), 2.29 (s, 3H); 13C NMR (125 MHz, CDCl3) δ ppm: 159.3, 151.8, 146.2, 139.1,
138.3, 130.8, 128.8, 126.7, 121.6, 117.9, 111.4, 111.0, 102.3, 29.7, 21.8, 12.8; Anal. Calcd for C21H18N2O3: C,
72.82; H, 5.24; N, 8.09. Found: C, 72.99; H, 5.07; N, 8.26; ESIꢀMS: m/z = 347 (M+1)+.
3-(1-(3,4-Difluorophenyl)-3-methyl-1H-pyrazol-5-yl)-7-methoxy-2H-chromen-2-one (4l). Yellow oil;
IR (KBr): 3103, 1739, 1658, 1610, 1520, 1454, 1398, 1025, 777, 697 cmꢀ1; 1H NMR (CDCl3, 500 MH
9
Z) δ

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ppm: 7.57 (s, 1H), 7.46ꢀ7.38 (m, 1H), 7.11 (d, J = 9.0 Hz, 2H), 7.11 (d, J = 5.5 Hz, 1H), 6.86 (d, J = 8.5 Hz,
1H), 6.82ꢀ6.81 (m, 1H), 6.46 (s, 1H), 3.88 (s, 3H), 2.36 (s, 3H); 13C NMR (125 MHz, CDCl3) δ ppm: 163.6,
159.2 (dd, JFC = 274.7, 13.2 Hz), 158.1 (dd, JFC = 252.9, 10.5 Hz), 155.8, 150.0, 142.9, 138.1, 137.2, 129.2
(dd, JFC = 10.4, 3.1 Hz), 120.2 (dd, JFC = 6.4, 3.7 Hz), 117.5 (d, JFC = 17.7 Hz), 115.0, 114.0 (d, JFC = 20.0
Hz), 113.3, 112.9, 112.1, 110.2, 108.7, 55.9, 13.5; Anal. Calcd for C20H14F2N2O3: C, 65.22; H, 3.83; N, 7.61.
Found: C, 65.39; H, 3.66; N, 7.78; ESIꢀMS: m/z = 369 (M+1)+.
3-(1-(4-Chloro-2-hydroxyphenyl)-3-methyl-1H-pyrazol-5-yl)-7-methoxy-2H-chromen-2-one (4m).
1
Yellow oil; IR (KBr): 3431, 2919, 1730, 1661, 1622, 1558, 1476, 1384, 1075, 715, 690 cmꢀ1; H NMR
(CDCl3, 500 MH ) δ ppm: 8.60 (s, 1H), 7.62ꢀ7.47 (m, 3H), 7.33ꢀ7.29 (m, 1H), 6.98 (s, 1H), 6.90 (d, J = 7.5
Z
Hz, 1H), 6.83 (s, 1H), 3.91 (s, 3H), 2.71 (s, 3H); 13C NMR (125 MHz, CDCl3) δ ppm: 164.9, 158.4, 156.8,
146.0, 145.6, 142.2, 134.2, 131.8, 130.8, 129.1, 128.8, 118.3, 118.1,116.9, 113.7, 112.4, 100.9, 100.2, 56.0,
27.2; Anal. Calcd for C20H15ClN2O4: C, 62.75; H, 3.95; N, 7.32. Found: C, 62.92; H, 3.78; N, 7.49; ESIꢀMS: m/z
= 383 (M+1)+.
3-(1-(Benzo[d]thiazol-2-yl)-3-methyl-1H-pyrazol-5-yl)-7-methoxy-2H-chromen-2-one (4n). Yellow oil;
IR (KBr): 3047, 1754, 1676, 1601, 1500, 1454, 1386, 1089, 756, 701 cmꢀ1; 1H NMR (CDCl3, 500 MH
) δ
Z
ppm: 8.53 (s, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.83 (d, J = 8.0 Hz, 1H), 7.37 (d, J = 8.0 Hz, 1H), 7.11 (s, 1H),
6.90 (d, J = 9.0 Hz, 2H), 6.87 (s, 1H), 6.84ꢀ6.83 (m, 1H), 3.91 (s, 3H), 2.88 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ ppm: 159.5, 154.7, 151.9, 147.8, 147.1, 145.8, 142.6, 141.6, 140.4, 139.3, 133.9, 130.9, 128.5,
126.3, 124.1, 122.7, 119.0, 117.3, 106.1, 22.7, 14.1; Anal. Calcd for C21H15N3O3S: C, 64.77; H, 3.88; N, 10.79.
Found: C, 64.94; H, 3.71; N, 10.96; ESIꢀMS: m/z = 390 (M+1)+.
7-Hydroxy-3-(3-methyl-1-phenyl-1H-pyrazol-5-yl)-2H-chromen-2-one (4o). White solid, 150ꢀ151
°C; IR (KBr): 3489, 3125, 1722, 1646, 1601, 1496, 1449, 1384, 1075, 750, 687 cmꢀ1; 1H NMR (CDCl3, 500
MH
) δ ppm: 7.30ꢀ7.28 (m, 5H), 7.24ꢀ7.23 (m, 3H), 6.89 (s, 1H), 6.87 (s, 1H), 1.62 (s, 3H); 13C NMR (125
Z
MHz, CDCl3) δ ppm: 156.0, 143.0, 139.2, 134.7, 132.4, 131.3, 129.6, 125.1, 121.3 120.3, 118.5, 112.7,
111.1, 29.7; Anal. Calcd for C19H14N2O3: C, 71.69; H, 4.43; N, 8.80. Found: C, 71.86; H, 4.26; N, 8.97; ESIꢀMS:
m/z = 319 (M+1)+.
3-(3-Methyl-1-phenyl-1H-pyrazol-5-yl)-6-nitro-2H-chromen-2-one (4p). White solid, 168ꢀ170 °C;
IR (KBr): 3041, 1727, 1635, 1599, 1502, 1464, 1383, 1046, 712, 692 cmꢀ1; 1H NMR (CDCl3, 500 MH
) δ
Z
ppm: 7.38 (s, 1H), 7.37 (s, 3H), 7.34ꢀ7.31 (m, 1H), 7.29 (t, J = 4.5 Hz, 1H), 7.25ꢀ7.24 (m, 1H), 7.23ꢀ7.21
(m, 1H), 7.00ꢀ6.97 (m, 1H), 6.62 (s, 1H), 2.38 (s, 3H); 13C NMR (125 MHz, CDCl3) δ ppm: 157.0, 155.1,
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153.1, 143.1, 139.6, 129.6, 121.2, 118.8, 118.7, 117.5, 117.4, 116.6, 116.4, 114.7, 114.5, 112.7,21.4; Anal.
Calcd for C19H13N3O4: C, 65.70; H, 3.77; N, 12.10. Found: C, 65.87; H, 3.60; N, 12.27; ESIꢀMS: m/z = 348
(M+1)+.
6-Chloro-3-(3-methyl-1-phenyl-1H-pyrazol-5-yl)-2H-chromen-2-one (4q). White solid, 175ꢀ177 °C;
IR (KBr): 3158, 1752, 1701, 1617, 1493, 1437, 1384, 1073, 713, 689 cmꢀ1; 1H NMR (CDCl3, 500 MH
) δ
Z
ppm: 7.94 (d, J = 8.0 Hz, 1H), 7.74ꢀ7.72 (m, 1H), 7.55ꢀ7.53 (m, 2H), 7.49 (s, 1H), 7.44 (t, J = 8.0 Hz, 2H),
7.37 (s, 1H), 7.09 (t, J = 8.5 Hz, 2H), 2.31 (s, 3H); 13C NMR (125 MHz, CDCl3) δ ppm: 156.9, 154.1, 149.6,
142.9, 140.9, 136.9, 134.7, 131.1, 127.8, 126.9, 122.6, 118.2, 117.6, 114.9, 112.1, 104.5, 21.0; Anal. Calcd
for C19H13ClN2O2: C, 67.76; H, 3.89; N, 8.32. Found: C, 67.93; H, 3.72; N, 8.49; ESIꢀMS: m/z = 337 (M+1)+.
7-Chloro-3-(1-(2-methoxyphenyl)-3-methyl-1H-pyrazol-5-yl)-2H-chromen-2-one (4r). White solid,
223ꢀ224 °C; IR (KBr): 3042, 1740, 1663, 1608, 1507, 1454, 1392, 1080, 778, 683 cmꢀ1; 1H NMR (CDCl3,
500 MH ) δ ppm: 8.41 (s, 1H), 7.47 (d, J = 7.5 Hz, 2H), 7.43 (d, J = 9.0 Hz, 1H), 7.38 (d, J = 7.5 Hz, 1H),
Z
7.29 (d, J = 8.5 Hz, 1H), 7.10 (d, J = 8.0 Hz, 1H), 7.07ꢀ7.05 (m, 2H), 3.83 (s, 3H), 2.18 (s, 3H); 13C NMR
(125 MHz, CDCl3) δ ppm: 154.6, 151.7, 145.0, 142.3, 135.8, 130.9, 130.7, 129.1, 127.1, 121.8 121.0, 120.8,
117.8, 112.1, 107.2, 29.7, 11.4; Anal. Calcd for C20H15ClN2O3: C, 65.49; H, 4.12; N, 7.64. Found: C, 65.66; H,
4.29; N, 7.81; ESIꢀMS: m/z = 367 (M+1)+.
6-Chloro-3-(3-methyl-1-(o-tolyl)-1H-pyrazol-5-yl)-2H-chromen-2-one (4s). White solid, 150ꢀ151 °C;
IR (KBr): 3095, 1740, 1661, 1602, 1502, 1454, 1380, 1083, 729, 690 cmꢀ1; 1H NMR (CDCl3, 500 MH
) δ
Z
ppm: 8.37 (s, 1H), 7.44 (s, 1H), 7.41 (t, J = 8.5 Hz, 2H), 7.38 (d, J = 7.0 Hz, 1H), 7.35 (d, J = 7.0 Hz, 1H),
7.32 (t, J = 7.5 Hz, 1H), 7.27 (t, J = 4.5 Hz, 1H), 7.06 (s, 1H), 2.14 (s, 3H), 2.08 (s, 3H); 13C NMR (125
MHz, CDCl3) δ ppm: 159.4, 151.7, 144.7, 141.0, 138.4, 136.0, 135.7, 131.2, 131.0, 129.7, 129.6, 127.7,
127.1, 126.8, 121.8, 120.7, 117.8, 107.2, 17.3, 11.5; Anal. Calcd for C20H15ClN2O2: C, 68.48; H, 4.31; N, 7.99.
Found: C, 68.65; H, 4.14; N, 8.16; ESIꢀMS: m/z = 351 (M+1)+.
6-Chloro-3-(3-methyl-1-(m-tolyl)-1H-pyrazol-5-yl)-2H-chromen-2-one (4t). White solid, 167ꢀ169
°C; IR (KBr): 2923, 1731, 1608, 1592, 1495, 1479, 1370, 1032, 695, 649 cmꢀ1; 1H NMR (CDCl3, 500 MH
δ ppm: 8.44 (s, 1H), 7.50ꢀ7.48 (m, 1H), 7.44 (d, J = 9.0 Hz, 1H), 7.39 (t, J = 7.5 Hz, 1H), 7.31 (d, J = 8.5
Z)
Hz, 2H), 7.28 (d, J = 6.5 Hz, 1H), 7.24 (s, 1H), 7.06 (s, 1H), 2.44 (s, 3H), 2.37 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ ppm: 159.4, 157.8, 144.7, 140.5, 139.5, 136.3, 131.6, 129.8, 129.2, 129.0, 127.3, 126.0, 122.2,
121.4, 120.7, 117.8, 108.6, 21.4, 12.5; Anal. Calcd for C20H15ClN2O2: C, 68.48; H, 4.31; N, 7.99. Found: C,
68.65; H, 4.14; N, 8.16; ESIꢀMS: m/z = 351 (M+1)+.
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6-Chloro-3-(1-(3,4-difluorophenyl)-3-methyl-1H-pyrazol-5-yl)-2H-chromen-2-one (4u). White solid,
223ꢀ225 °C; IR (KBr): 3020, 1750, 1702, 1623, 1500, 1465, 1384, 1038, 717, 696 cmꢀ1; 1H NMR (CDCl3,
500 MH ) δ ppm: 8.40 (s, 1H), 7.53ꢀ7.52 (m, 1H), 7.46 (d, J = 8.5 Hz, 1H), 7.42ꢀ7.39 (m, 1H), 7.31 (d,J =
Z
8.5 Hz, 2H), 7.23ꢀ7.17 (m, 1H), 7.08 (s, 1H), 2.39 (s, 3H); 13C NMR (125 MHz, CDCl3) δ ppm: 163.2 (dd,
JFC = 258.6, 11.1 Hz), 159.4 (dd, JFC = 258.2, 14.5 Hz), 159.3, 151.8, 145.4, 140.3, 136.3, 131.3, 129.8, 127.3,
121.3, 121.0 (dd, JFC = 6.4, 3.7 Hz), 120.6, 117.9 (dd, JFC = 7.5, 3.1 Hz), 117.7 (d, JFC = 18.5 Hz), 114.8 (d,
JFC = 19.6 Hz), 109.1, 12.5; Anal. Calcd for C19H11ClF2N2O2: C, 61.22; H, 2.97; N, 7.52. Found: C, 61.39; H,
2.80; N, 7.69; ESIꢀMS: m/z = 373 (M+1)+.
3-(1-(4-Bromophenyl)-3-methyl-1H-pyrazol-5-yl)-6-chloro-2H-chromen-2-one (4v). White solid,
227ꢀ229 °C; IR (KBr): 3030, 1745, 1666, 1600, 1505, 1460, 1381, 1080, 755, 699 cmꢀ1; 1H NMR (CDCl3,
500 MH ) δ ppm: 8.43 (s, 1H), 7.67 (d, J = 8.5 Hz, 2H), 7.54 (s, 1H), 7.48 (d, J = 9.0 Hz, 1H), 7.42 (d,J =
Z
9.0 Hz, 2H), 7.33 (d, J = 9.0 Hz, 1H), 7.10 (s, 1H), 2.41 (s, 3H); 13C NMR (125 MHz, CDCl3) δ ppm: 159.4,
151.8, 145.3, 140.2, 136.1, 132.4, 131.2, 129.8, 128.5, 127.2, 126.5, 121.9, 121.5, 120.6, 117.8, 109.1, 12.5;
Anal. Calcd for C19H12BrClN2O2: C, 54.90; H, 2.91; N, 6.74. Found: C, 55.07; H, 2.74; N, 6.91; ESIꢀMS: m/z =
415 (M+1)+.
6-Chloro-3-(3-methyl-1H-pyrazol-5-yl)-2H-chromen-2-one (4w). White solid, 177ꢀ179 °C; IR
(KBr): 3415, 3055, 1740, 1612, 1554, 1465, 1377, 1018, 731, 692 cmꢀ1; 1H NMR (CDCl3, 500 MH
) δ ppm:
Z
8.55 (s, 1H), 7.62 (d, J = 2.0 Hz, 1H), 7.58ꢀ7.56 (m, 1H), 7.31 (d, J = 9.0 Hz, 1H), 7.00 (s, 1H), 2.27 (s,
3H); 13C NMR (125 MHz, CDCl3) δ ppm: 164.1, 157.4, 152.7, 144.0, 133.8, 130.3, 128.5, 121.8, 119.5,
118.0, 101.9, 29.7; Anal. Calcd for C13H9ClN2O2: C, 59.90; H, 3.48; N, 10.75. Found: C, 60.07; H, 3.31; N,
10.92; ESIꢀMS: m/z = 261 (M+1)+.
6-Chloro-3-(3-methyl-1-(pyridin-2-yl)-1H-pyrazol-5-yl)-2H-chromen-2-one (4x). White solid,
168ꢀ169 °C; IR (KBr): 2962, 1735, 1629, 1593, 1580, 1476, 1383, 1035, 713, 700 cmꢀ1; 1H NMR (CDCl3,
500 MH ) δ ppm: 8.30 (d, J = 4.5 Hz, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.85 (t, J = 7.5 Hz, 1H), 7.77 (d, J = 8.0
Z
Hz, 1H), 7.72ꢀ7.70 (m, 1H), 7.53ꢀ7.51 (m, 1H), 7.31 (s, 1H), 7.12ꢀ7.09 (m, 1H), 6.16 (s, 1H), 2.34 (s, 3H);
13C NMR (125 MHz, CDCl3) δ ppm: 156.9, 140.9, 138.0, 135.7, 131.1, 129.5, 129.2, 127.0 123.2, 121.7,
120.8, 119.9, 118.9, 116.4, 112.7, 101.4, 27.2; Anal. Calcd for C18H12ClN3O2: C, 64.01; H, 3.58; N, 12.44.
Found: C, 64.18; H, 3.41; N, 12.61; ESIꢀMS: m/z = 338 (M+1)+.
7-Bromo-3-(3-methyl-1-phenyl-1H-pyrazol-5-yl)-2H-chromen-2-one (4y). White solid, 162ꢀ163 °C
1
(Lit. 160ꢀ162 °C)23; IR (KBr): 3030, 1773, 1628, 1598, 1500, 1443, 1390, 1071, 748, 691 cmꢀ1; H NMR
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(CDCl3, 500 MH ) δ ppm: 7.81 (s, 1H), 7.36 (s, 1H), 7.29 (t, J = 7.5 Hz, 2H), 7.00 (d, J = 8.5 Hz, 1H), 6.95
Z
(d, J = 8.0 Hz, 2H), 6.90 (t, J = 7.5 Hz, 1H), 6.47 (s, 1H), 6.39 (s, 1H), 2.71 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ ppm: 156.5, 150.3, 146.1, 143.5, 140.1, 138.7, 133.7, 131.5, 129.1, 126.0, 125.7, 124.7, 121.3,
116.7, 113.7, 111.4, 30.8; Anal. Calcd for C19H13BrN2O2: C, 59.86; H, 3.44; N, 7.35. Found: C, 60.03; H, 3.27;
N, 7.52; ESIꢀMS: m/z = 381 (M+1)+
6-Bromo-3-(3-methyl-1-(2,4,6-trichlorophenyl)-1H-pyrazol-5-yl)-2H-chromen-2-one (4z). White
1
solid, 170ꢀ172 °C; IR (KBr): 3015, 1735, 1640, 1593, 1561, 1476, 1384, 1054, 780, 737, 700 cmꢀ1; H
NMR (CDCl3, 500 MH ) δ ppm: 7.73 (s, 1H), 7.46 (s, 1H), 7.21 (d, J = 6.5 Hz, 1H), 7.16 (d, J = 5.5 Hz,
Z
2H), 6.75 (d, J = 8.5 Hz, 2H), 2.06 (s, 3H); 13C NMR (125 MHz, CDCl3) δ ppm: 156.7, 143.5, 135.7, 133.3,
132.0, 129.3, 129.1, 127.1, 119.5, 118.7, 110.9, 30.7; Anal. Calcd for C19H10BrCl3N2O2: C, 47.10; H, 2.08; N,
5.78. Found: C, 47.27; H, 1.91; N, 5.95; ESIꢀMS: m/z = 483 (M+1)+.
7-Bromo-3-(1-(4-chloro-2-hydroxyphenyl)-3-methyl-1H-pyrazol-5-yl)-2H-chromen-2-one (4aa).
1
Yellow oil; IR (KBr): 3516, 2975, 1727, 1685, 1611, 1501, 1474, 1360, 1080, 770, 639 cmꢀ1; H NMR
(CDCl3, 500 MH ) δ ppm: 8.41 (s, 1H), 7.93 (s, 1H), 7.74ꢀ7.73 (m, 1H), 7.71ꢀ7.70 (m, 1H), 7.47 (d, J = 5.0
Z
Hz, 1H), 7.44 (s, 1H), 7.41 (s, 1H), 6.45 (d, J = 9.5 Hz, 1H), 2.71 (s, 3H); 13C NMR (125 MHz, CDCl3) δ
ppm: 153.4, 152.5, 147.1, 142.2, 137.2, 136.3, 134.6, 134.3, 131.6, 131.2, 130.2, 129.1, 128.2, 126.4, 118.7,
118.5, 101.6, 15.3; Anal. Calcd for C19H12BrClN2O3: C, 52.87; H, 2.80; N, 6.49. Found: C, 53.04; H, 2.63; N,
6.66; ESIꢀMS: m/z = 413 (M+1)+.
2-(3-Methyl-1-phenyl-1H-pyrazol-5-yl)-3H-benzo[f]chromen-3-one (4ab). White solid, 186ꢀ188 °C;
IR (KBr): 2976, 1732, 1713, 1605, 1495, 1468, 1384, 1049 cmꢀ1; 1H NMR (CDCl3, 500 MH
) δ ppm: 8.77
Z
(s, 1H), 8.37 (d, J = 8.5 Hz, 1H), 8.07 (d, J = 9.0 Hz, 1H), 7.98 (d, J = 9.0 Hz, 1H), 7.92 (d, J = 8.0 Hz, 1H),
7.77ꢀ7.71 (m, 3H), 7.60 (t, J = 7.0 Hz, 1H), 7.50ꢀ7.45 (m, 2H), 7.22 (d, J = 9.0 Hz, 1H), 7.09 (s, 1H), 2.27
(s, 3H); 13C NMR (125 MHz, CDCl3) δ ppm: 159.9, 155.4, 151.3, 149.1, 147.5, 146.9, 145.0, 143.9, 138.4,
130.9, 128.8, 117.9, 114.4, 110.6, 107.6, 30.9; Anal. Calcd for C23H16N2O2: C, 78.39; H, 4.58; N, 7.95. Found:
C, 78.56; H, 4.41; N, 8.12; ESIꢀMS: m/z = 353 (M+1)+.
2-(3-Methyl-1-(m-tolyl)-1H-pyrazol-5-yl)-3H-benzo[f]chromen-3-one (4ac). White solid, 201ꢀ202
°C; IR (KBr): 3120 ,1731, 1663, 1600, 1517, 1454, 1397, 1050, 740, 689 cmꢀ1; 1H NMR (CDCl3, 500 MH
)
Z
δ ppm: 9.28 (s, 1H), 8.43 (d, J = 8.5 Hz, 1H), 7.95 (d, J = 9.0 Hz, 1H), 7.89 (d, J = 8.0 Hz, 1H), 7.66 (t,J =
8.0 Hz, 1H), 7.55 (t, J = 8.0 Hz, 1H), 7.49 (d, J = 9.0 Hz, 1H), 7.42 (d, J = 8.0 Hz, 1H), 7.39 (s, 1H), 7.32
(d, J = 8.0 Hz, 1H), 7.27 (s, 1H), 7.14 (s, 1H), 2.47 (s, 3H), 2.39 (s, 3H); 13C NMR (125 MHz, CDCl3) δ
13

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ppm: 160.1, 153.0, 145.6, 140.1, 139.6, 139.4, 133.3, 132.5, 130.4, 129.3, 128.9, 128.8, 128.0, 126.0, 122.2,
119.6, 113.9, 108.4, 21.4, 12.5; Anal. Calcd for C24H18N2O2: C, 78.67; H, 4.95; N, 7.65. Found: C, 78.84; H,
4.78; N, 7.82; ESIꢀMS: m/z = 367 (M+1)+.
2-(3-Methyl-1-(2,4,6-trichlorophenyl)-1H-pyrazol-5-yl)-3H-benzo[f]chromen-3-one (4ad). White
1
solid, 200ꢀ201 °C; IR (KBr): 3057, 1760, 1698, 1601, 1500, 1466, 1384, 1034, 778, 725 cmꢀ1; H NMR
(CDCl3, 500 MH ) δ ppm: 8.37 (d, J = 8.5 Hz, 1H), 8.07 (d, J = 9.0 Hz, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.66
Z
(d, J = 8.5 Hz, 1H), 7.61 (t, J = 7.5 Hz, 1H), 7.46 (d, J = 9.0 Hz, 1H), 7.41 (t, J = 8.0 Hz, 1H), 7.31 (t, J =
8.0 Hz, 1H), 7.15 (s, 1H), 7.11 (s, 1H), 2.29 (s, 3H); 13C NMR (125 MHz, CDCl3) δ ppm: 158.3, 141.1,
135.8, 129.8, 129.2, 129.1, 127.5, 126.6, 126.5, 126.3, 123.5, 121.8, 117.8, 116.5, 113.1, 109.5, 101.5, 27.4
;
Anal. Calcd for C23H13Cl3N2O2: C, 60.62; H, 2.88; N, 6.15. Found: C, 60.79; H, 2.71; N, 6.32; ESIꢀMS: m/z =
455 (M+1)+.
2-(3-Methyl-1-(pyridin-2-yl)-1H-pyrazol-5-yl)-3H-benzo[f]chromen-3-one (4ae). White solid,
198ꢀ200 °C; IR (KBr): 3015, 1732, 1667, 1610, 1512, 1454, 1400, 1075 cmꢀ1; 1H NMR (CDCl3, 500 MH
)
Z
δ ppm: 9.35 (s, 1H), 8.51 (t, J = 5.0 Hz, 1H), 8.46 (d, J = 8.5 Hz, 1H), 8.05 (d, J = 8.5 Hz, 1H), 7.99 (d,J =
8.5 Hz, 1H), 7.92 (d, J = 7.5 Hz, 1H), 7.89 (t, J = 7.0 Hz, 1H), 7.71 (s, 1H), 7.58 (t, J = 7.5 Hz, 1H), 7.51 (d,
J = 9.0 Hz, 1H), 7.48 (d, J = 9.0 Hz, 1H), 7.14 (s, 1H), 2.75 (s, 3H); 13C NMR (125 MHz, CDCl3) δ ppm:
154.4, 147.8, 138.5, 138.4, 133.8, 131.0, 129.5, 129.0, 128.3, 127.9, 127.7, 126.3, 126.2, 125.8, 123.1,
121.7, 118.3, 116.7, 109.4, 14.1; Anal. Calcd for C22H15N3O2: C, 74.78; H, 4.28; N, 11.89. Found: C, 74.95; H,
4.11; N, 12.06; ESIꢀMS: m/z = 354 (M+1)+.
Acknowledgements
We are thankful to the National Natural Science Foundation of China (No. 21272053) and the
Nature Science Foundation of Hebei Province (No. B2015205182) for financial support of
this research.
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