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DOI: 10.1039/C5RA01677K (Paper) RSC Adv., 2015, 5, 25625-25633

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

Xiao-Tang Lia, Yu-Heng Liub, Xin Liua and Zhan-Hui Zhang*a
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, P. R. China

Received 28th January 2015 , Accepted 5th March 2015

First published on 5th March 2015

Abstract

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 meglumine as a catalyst in aqueous–ethanol media. This new protocol offers several advantages including the use of a biodegradable and inexpensive catalyst, short reaction time, high yields, and simple work-up procedure.

Introduction

Currently, multicomponent reactions (MCRs) are becoming powerful and valuable synthetic strategies in modern organic and medicinal chemistry because they allow 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 of convenient, safe, atom-economic, high-yielding, and environmentally benign procedures and reduce the generation of chemical waste.1–4 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, bio-compatibility and bio-degradability, low cost and non-corrosive nature. It was previously reported by Gu as a promoting medium with gluconic acid aqueous solution for the hydroxymethylation of β-ketosulfones with formaldehyde.12 Meglumine contains an 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.

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 one-pot, three-component coupling (TCC) reaction of salicylaldehyde, 4-hydroxy-6-methyl-2H-pyran-2-one and hydrazine using meglumine as a biodegradable catalyst (Scheme 1).


image file: c5ra01677k-s1.tif
Scheme 1 One-pot, three-component synthesis of pyrazolylcoumarins catalyzed by meglumine.

Results and discussion

Initially, salicylaldehydes, 1,4-hydroxy-6-methyl-2H-pyran-2-one 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 L-proline as catalyst in a mixture of EtOH–H2O. When CaCO3, piperidine, 1,3-dimethylurea, 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 3–14). 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 three-component reaction and afforded the desired product 4a in an isolated yield of 80% within 1.5 h (Table 1, entry 17).
Table 1 Optimization of the reaction conditions for the synthesis of 4aa

image file: c5ra01677k-u1.tif
Entry Catalyst Solvent Temp (°C) Time (min) Yieldb (%)
a Experimental conditions: salicylaldehyde (1 mmol), 4-hydroxy-6-methyl-2H-pyran-2-one (1 mmol), phenylhydrazine (1 mmol), catalyst (0.2 mmol), solvent (4 mL).b Isolated yield.
1 None Ethanol Reflux 720 0
2 None Ethanol[thin space (1/6-em)]:[thin space (1/6-em)]H2O (1[thin space (1/6-em)]:[thin space (1/6-em)]1) Reflux 720 0
3 Fe2O3 Ethanol[thin space (1/6-em)]:[thin space (1/6-em)]H2O (1[thin space (1/6-em)]:[thin space (1/6-em)]1) Reflux 720 Trace
4 L-Proline Ethanol[thin space (1/6-em)]:[thin space (1/6-em)]H2O (1[thin space (1/6-em)]:[thin space (1/6-em)]1) Reflux 720 Trace
5 CaCO3 Ethanol[thin space (1/6-em)]:[thin space (1/6-em)]H2O (1[thin space (1/6-em)]:[thin space (1/6-em)]1) Reflux 360 20
6 Piperidine Ethanol[thin space (1/6-em)]:[thin space (1/6-em)]H2O (1[thin space (1/6-em)]:[thin space (1/6-em)]1) Reflux 360 40
7 1,3-Dimethylurea Ethanol[thin space (1/6-em)]:[thin space (1/6-em)]H2O (1[thin space (1/6-em)]:[thin space (1/6-em)]1) Reflux 360 38
8 Chitosan Ethanol[thin space (1/6-em)]:[thin space (1/6-em)]H2O (1[thin space (1/6-em)]:[thin space (1/6-em)]1) Reflux 360 35
9 Betaine HCl Ethanol[thin space (1/6-em)]:[thin space (1/6-em)]H2O (1[thin space (1/6-em)]:[thin space (1/6-em)]1) Reflux 360 20
10 Mannitol Ethanol[thin space (1/6-em)]:[thin space (1/6-em)]H2O (1[thin space (1/6-em)]:[thin space (1/6-em)]1) Reflux 360 30
11 DMAP Ethanol[thin space (1/6-em)]:[thin space (1/6-em)]H2O (1[thin space (1/6-em)]:[thin space (1/6-em)]1) Reflux 360 42
12 DBU Ethanol[thin space (1/6-em)]:[thin space (1/6-em)]H2O (1[thin space (1/6-em)]:[thin space (1/6-em)]1) Reflux 360 60
13 Et3N Ethanol[thin space (1/6-em)]:[thin space (1/6-em)]H2O (1[thin space (1/6-em)]:[thin space (1/6-em)]1) Reflux 360 56
14 DABCO Ethanol[thin space (1/6-em)]:[thin space (1/6-em)]H2O (1[thin space (1/6-em)]:[thin space (1/6-em)]1) Reflux 360 68
15 Choline chloride[thin space (1/6-em)]:[thin space (1/6-em)]urea (1[thin space (1/6-em)]:[thin space (1/6-em)]2)   80 360 42
16 Citric acid[thin space (1/6-em)]:[thin space (1/6-em)]DMU (40[thin space (1/6-em)]:[thin space (1/6-em)]60)   80 360 30
17 Meglumine Ethanol[thin space (1/6-em)]:[thin space (1/6-em)]H2O (1[thin space (1/6-em)]:[thin space (1/6-em)]1) Reflux 90 80
18 Meglumine H2O Reflux 720 Trace
19 Meglumine Glycerin Reflux 720 40
20 Meglumine Glycerin[thin space (1/6-em)]:[thin space (1/6-em)]ethanol (1[thin space (1/6-em)]:[thin space (1/6-em)]2) Reflux 720 48
21 Meglumine Glycerin[thin space (1/6-em)]:[thin space (1/6-em)]H2O (1[thin space (1/6-em)]:[thin space (1/6-em)]3) Reflux 360 56
22 Meglumine PEG400 100 360 45
23 Piperidine CH3CN Reflux 360 36
24 Meglumine Ethanol Reflux 90 70
25 Meglumine (0.1 mmol) Ethanol[thin space (1/6-em)]:[thin space (1/6-em)]H2O (1[thin space (1/6-em)]:[thin space (1/6-em)]1) Reflux 90 65
26 Meglumine (0.4 mmol) Ethanol[thin space (1/6-em)]:[thin space (1/6-em)]H2O (1[thin space (1/6-em)]:[thin space (1/6-em)]1) Reflux 60 60
27 Meglumine (0.4 mmol) Ethanol[thin space (1/6-em)]:[thin space (1/6-em)]H2O (1[thin space (1/6-em)]:[thin space (1/6-em)]1) Reflux 90 80
28 Meglumine (0.4 mmol) Ethanol[thin space (1/6-em)]:[thin space (1/6-em)]H2O (1[thin space (1/6-em)]:[thin space (1/6-em)]1) Reflux 360 80
29 Meglumine (0.3 mmol) Ethanol[thin space (1/6-em)]:[thin space (1/6-em)]H2O (1[thin space (1/6-em)]:[thin space (1/6-em)]1) Reflux 90 80

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 aqueous–ethanol (1[thin space (1/6-em)]:[thin space (1/6-em)]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, 4-hydroxy-6-methyl-2H-pyran-2-one (1 mmol), and phenylhydrazine (1 mmol) with meglumine (0.2 mmol) in aqueous–ethanol (1[thin space (1/6-em)]:[thin space (1/6-em)]1 v/v, 4 mL) under reflux for 1.5 h (Table 1, entry 17).

Under the optimized reaction conditions, the scope of this three-component reaction was considerably expanded and the results are summarized in Fig. 1. Various arylhydrazines bearing electron-donating group (EDG) and electron-withdrawing group (EWG) underwent the reaction with salicylaldehydes and 4-hydroxy-6-methyl-2H-pyran-2-one 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 (4-nitrophenyl)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 2-hydrazinylpyridine worked well, providing high yield of expected 4h. Fortunately, 2-hydrazinylbenzo[d]thiazole also proceeded efficiently, producing the corresponding product 4n in 70% isolated yield.


image file: c5ra01677k-f1.tif
Fig. 1 Scope of pyrazolylcoumarin synthesis.

Inspired by these encouraging results, we next explored the scope of this MCR process with respect to salicylaldehydes. As anticipated, salicylaldehydes bearing either electron-donating or electron-withdrawing 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 electron-withdrawing substituted salicylaldehydes showed better reactivity than the electron-donating substituted salicylaldehydes. Furthermore, 2-hydroxy-1-naphthaldehyde participated in the reaction smoothly and delivered the products 4ab–4ae in 70–86% yield, respectively.

A proposed mechanism for the synthesis of 3-(3-methyl-1-phenyl-1H-pyrazol-5-yl)-2H-chromen-2-one (4a) from salicylaldehyde, 4-hydroxy-6-methyl-2H-pyran-2-one, and phenylhydrazine catalyzed by meglumine is shown in Scheme 2. We reasoned that in the presence of meglumine, Knoevenagel condensation of salicylaldehyde and 4-hydroxy-6-methyl-2H-pyran-2-one 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.


image file: c5ra01677k-s2.tif
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 one-pot three-component reaction of salicylaldehyde, 4-hydroxy-6-methyl-2H-pyran-2-one, and hydrazine by using meglumine as an inexpensive, biodegradable catalyst in aqueous–ethanol 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 points were determined using an X-4 apparatus and are uncorrected. IR spectra were taken as KBr discs with a Thermo Fisher Scientific Nicolet iS50 spectrometer. 1H and 13C NMR spectra were recorded on a Bruker DRX-500 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 pyrazole substituted derivatives

To a mixture of ethyl salicylaldehyde (1 mmol) and 4-hydroxy-6-methyl-2H-pyran-2-one (1 mmol) in ethanol–H2O (1[thin space (1/6-em)]:[thin space (1/6-em)]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[thin space (1/6-em)]:[thin space (1/6-em)]9).

Characterization data

3-(3-Methyl-1-phenyl-1H-pyrazol-5-yl)-2H-chromen-2-one (4a). White solid, 130–131 °C (Lit. 126–127 °C);23 IR (KBr): 3032, 1780, 1680, 1620, 1500, 1465, 1386, 1012 cm−1; 1H NMR (CDCl3, 500 MHZ) δ ppm: 7.55–7.52 (m, 1H), 7.46 (s, 1H), 7.42–7.40 (m, 3H), 7.38 (s, 1H), 7.34–7.31 (m, 3H), 7.24 (d, J = 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%; ESI-MS: m/z = 303 (M + 1)+.
3-(1-(2-Methoxyphenyl)-3-methyl-1H-pyrazol-5-yl)-2H-chromen-2-one (4b). White solid, 191–192 °C; IR (KBr): 3015, 1738, 1661, 1613, 1516, 1453, 1389, 1163, 756, 693 cm−1; 1H NMR (CDCl3, 500 MHZ) δ 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%; ESI-MS: m/z = 333 (M + 1)+.
3-(3-Methyl-1-(o-tolyl)-1H-pyrazol-5-yl)-2H-chromen-2-one (4c). White solid, 149–150 °C; IR (KBr): 3119, 1745, 1638, 1612, 1496, 1454, 1398, 1165, 750, 709 cm−1; 1H NMR (CDCl3, 500 MHZ) δ ppm: 8.50 (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 = 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); 13C 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%; ESI-MS: 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): 3001, 1767, 1654, 1630, 1496, 1460, 1384, 1048 cm−1; 1H NMR (CDCl3, 500 MHZ) δ ppm: 8.51 (s, 1H), 7.55 (d, J = 7.5 Hz, 1H), 7.51 (t, J = 7.5 Hz, 1H), 7.40–7.35 (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%; ESI-MS: m/z = 317 (M + 1)+.
3-(1-(3,4-Difluorophenyl)-3-methyl-1H-pyrazol-5-yl)-2H-chromen-2-one (4e). White solid, 209–210 °C; IR (KBr): 3032, 1750, 1668, 1600, 1502, 1543, 1381, 1050, 700 cm−1; 1H NMR (CDCl3, 500 MHZ) 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), 7.30–7.27 (m, 2H), 7.07 (s, 1H), 6.99–6.89 (m, 1H), 2.38 (s, 3H); 13C 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%; ESI-MS: m/z = 339 (M + 1)+.
3-(1-(4-Bromophenyl)-3-methyl-1H-pyrazol-5-yl)-2H-chromen-2-one (4f). White solid, 212–213 °C; IR (KBr): 3013, 1724, 1661, 1611, 1494, 1454, 1340, 1070, 753, 690 cm−1; 1H NMR (CDCl3, 500 MHZ) δ ppm: 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%; ESI-MS: m/z = 381 (M + 1)+.
3-(3-Methyl-1H-pyrazol-5-yl)-2H-chromen-2-one (4g). White solid, 180–181 °C (Lit. 182 °C);23 IR (KBr): 3432, 2954, 1728, 1713, 1610, 1554, 1459, 1394, 1032 cm−1; 1H NMR (CDCl3, 500 MHZ) 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, 69.19; H, 4.29; N, 12.55%; ESI-MS: m/z = 227 (M + 1)+.
3-(3-Methyl-1-(pyridin-2-yl)-1H-pyrazol-5-yl)-2H-chromen-2-one (4h). White solid, 158–160 °C; IR (KBr): 3018, 1735, 1640, 1600, 1593, 1475, 1384, 1054 cm−1; 1H NMR (CDCl3, 500 MHZ) δ ppm: 8.18 (d, J = 4.5 Hz, 1H), 7.94 (s, 1H), 7.65 (t, J = 7.0 Hz, 1H), 7.55–7.51 (m, 1H), 7.37–7.33 (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%; ESI-MS: 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 cm−1; 1H NMR (CDCl3, 500 MHZ) δ ppm: 8.48 (s, 1H), 7.75–7.73 (m, 1H), 7.56–7.54 (m, 1H), 7.54–7.53 (m, 3H), 7.48–7.44 (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%; ESI-MS: m/z = 333 (M + 1)+.
6-Methoxy-3-(3-methyl-1-(o-tolyl)-1H-pyrazol-5-yl)-2H-chromen-2-one (4j). White solid, 148–150 °C; IR (KBr): 3003, 1742, 1663, 1609, 1514, 1454, 1333, 1088, 778, 700 cm−1; 1H NMR (CDCl3, 500 MHZ) δ 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%; ESI-MS: m/z = 347 (M + 1)+.
7-Methoxy-3-(3-methyl-1-(m-tolyl)-1H-pyrazol-5-yl)-2H-chromen-2-one (4k). White solid, 163–165 °C; IR (KBr): 3007, 1735, 1700, 1631, 1507, 1465, 1384, 1049, 728, 695 cm−1; 1H NMR (CDCl3, 500 MHZ) δ ppm: 7.61 (s, 1H), 7.58 (d, J = 8.5 Hz, 1H), 7.53–7.42 (m, 1H), 7.34 (t, J = 7.5 Hz, 1H), 7.30 (t, 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%; ESI-MS: 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 cm−1; 1H NMR (CDCl3, 500 MHZ) δ ppm: 7.57 (s, 1H), 7.46–7.38 (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), 6.82–6.81 (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%; ESI-MS: m/z = 369 (M + 1)+.
3-(1-(4-Chloro-2-hydroxyphenyl)-3-methyl-1H-pyrazol-5-yl)-7-methoxy-2H-chromen-2-one (4m). Yellow oil; IR (KBr): 3431, 2919, 1730, 1661, 1622, 1558, 1476, 1384, 1075, 715, 690 cm−1; 1H NMR (CDCl3, 500 MHZ) δ ppm: 8.60 (s, 1H), 7.62–7.47 (m, 3H), 7.33–7.29 (m, 1H), 6.98 (s, 1H), 6.90 (d, J = 7.5 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%; ESI-MS: 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 cm−1; 1H NMR (CDCl3, 500 MHZ) δ 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), 6.84–6.83 (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%; ESI-MS: m/z = 390 (M + 1)+.
7-Hydroxy-3-(3-methyl-1-phenyl-1H-pyrazol-5-yl)-2H-chromen-2-one (4o). White solid, 150–151 °C; IR (KBr): 3489, 3125, 1722, 1646, 1601, 1496, 1449, 1384, 1075, 750, 687 cm−1; 1H NMR (CDCl3, 500 MHZ) δ ppm: 7.30–7.28 (m, 5H), 7.24–7.23 (m, 3H), 6.89 (s, 1H), 6.87 (s, 1H), 1.62 (s, 3H); 13C NMR (125 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%; ESI-MS: m/z = 319 (M + 1)+.
3-(3-Methyl-1-phenyl-1H-pyrazol-5-yl)-6-nitro-2H-chromen-2-one (4p). White solid, 168–170 °C; IR (KBr): 3041, 1727, 1635, 1599, 1502, 1464, 1383, 1046, 712, 692 cm−1; 1H NMR (CDCl3, 500 MHZ) δ ppm: 7.38 (s, 1H), 7.37 (s, 3H), 7.34–7.31 (m, 1H), 7.29 (t, J = 4.5 Hz, 1H), 7.25–7.24 (m, 1H), 7.23–7.21 (m, 1H), 7.00–6.97 (m, 1H), 6.62 (s, 1H), 2.38 (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, 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%; ESI-MS: m/z = 348 (M + 1)+.
6-Chloro-3-(3-methyl-1-phenyl-1H-pyrazol-5-yl)-2H-chromen-2-one (4q). White solid, 175–177 °C; IR (KBr): 3158, 1752, 1701, 1617, 1493, 1437, 1384, 1073, 713, 689 cm−1; 1H NMR (CDCl3, 500 MHZ) δ ppm: 7.94 (d, J = 8.0 Hz, 1H), 7.74–7.72 (m, 1H), 7.55–7.53 (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%; ESI-MS: m/z = 337 (M + 1)+.
7-Chloro-3-(1-(2-methoxyphenyl)-3-methyl-1H-pyrazol-5-yl)-2H-chromen-2-one (4r). White solid, 223–224 °C; IR (KBr): 3042, 1740, 1663, 1608, 1507, 1454, 1392, 1080, 778, 683 cm−1; 1H NMR (CDCl3, 500 MHZ) 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), 7.29 (d, J = 8.5 Hz, 1H), 7.10 (d, J = 8.0 Hz, 1H), 7.07–7.05 (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%; ESI-MS: m/z = 367 (M + 1)+.
6-Chloro-3-(3-methyl-1-(o-tolyl)-1H-pyrazol-5-yl)-2H-chromen-2-one (4s). White solid, 150–151 °C; IR (KBr): 3095, 1740, 1661, 1602, 1502, 1454, 1380, 1083, 729, 690 cm−1; 1H NMR (CDCl3, 500 MHZ) δ 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%; ESI-MS: m/z = 351 (M + 1)+.
6-Chloro-3-(3-methyl-1-(m-tolyl)-1H-pyrazol-5-yl)-2H-chromen-2-one (4t). White solid, 167–169 °C; IR (KBr): 2923, 1731, 1608, 1592, 1495, 1479, 1370, 1032, 695, 649 cm−1; 1H NMR (CDCl3, 500 MHZ) δ ppm: 8.44 (s, 1H), 7.50–7.48 (m, 1H), 7.44 (d, J = 9.0 Hz, 1H), 7.39 (t, J = 7.5 Hz, 1H), 7.31 (d, J = 8.5 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%; ESI-MS: m/z = 351 (M + 1)+.
6-Chloro-3-(1-(3,4-difluorophenyl)-3-methyl-1H-pyrazol-5-yl)-2H-chromen-2-one (4u). White solid, 223–225 °C; IR (KBr): 3020, 1750, 1702, 1623, 1500, 1465, 1384, 1038, 717, 696 cm−1; 1H NMR (CDCl3, 500 MHZ) δ ppm: 8.40 (s, 1H), 7.53–7.52 (m, 1H), 7.46 (d, J = 8.5 Hz, 1H), 7.42–7.39 (m, 1H), 7.31 (d, J = 8.5 Hz, 2H), 7.23–7.17 (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%; ESI-MS: m/z = 373 (M + 1)+.
3-(1-(4-Bromophenyl)-3-methyl-1H-pyrazol-5-yl)-6-chloro-2H-chromen-2-one (4v). White solid, 227–229 °C; IR (KBr): 3030, 1745, 1666, 1600, 1505, 1460, 1381, 1080, 755, 699 cm−1; 1H NMR (CDCl3, 500 MHZ) 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 = 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%; ESI-MS: m/z = 415 (M + 1)+.
6-Chloro-3-(3-methyl-1H-pyrazol-5-yl)-2H-chromen-2-one (4w). White solid, 177–179 °C; IR (KBr): 3415, 3055, 1740, 1612, 1554, 1465, 1377, 1018, 731, 692 cm−1; 1H NMR (CDCl3, 500 MHZ) δ ppm: 8.55 (s, 1H), 7.62 (d, J = 2.0 Hz, 1H), 7.58–7.56 (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%; ESI-MS: 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, 168–169 °C; IR (KBr): 2962, 1735, 1629, 1593, 1580, 1476, 1383, 1035, 713, 700 cm−1; 1H NMR (CDCl3, 500 MHZ) 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 Hz, 1H), 7.72–7.70 (m, 1H), 7.53–7.51 (m, 1H), 7.31 (s, 1H), 7.12–7.09 (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%; ESI-MS: m/z = 338 (M + 1)+.
7-Bromo-3-(3-methyl-1-phenyl-1H-pyrazol-5-yl)-2H-chromen-2-one (4y). White solid, 162–163 °C (Lit. 160–162 °C);23 IR (KBr): 3030, 1773, 1628, 1598, 1500, 1443, 1390, 1071, 748, 691 cm−1; 1H NMR (CDCl3, 500 MHZ) 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 (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%; ESI-MS: 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 solid, 170–172 °C; IR (KBr): 3015, 1735, 1640, 1593, 1561, 1476, 1384, 1054, 780, 737, 700 cm−1; 1H NMR (CDCl3, 500 MHZ) 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, 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%; ESI-MS: m/z = 483 (M + 1)+.
7-Bromo-3-(1-(4-chloro-2-hydroxyphenyl)-3-methyl-1H-pyrazol-5-yl)-2H-chromen-2-one (4aa). Yellow oil; IR (KBr): 3516, 2975, 1727, 1685, 1611, 1501, 1474, 1360, 1080, 770, 639 cm−1; 1H NMR (CDCl3, 500 MHZ) δ ppm: 8.41 (s, 1H), 7.93 (s, 1H), 7.74–7.73 (m, 1H), 7.71–7.70 (m, 1H), 7.47 (d, J = 5.0 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%; ESI-MS: m/z = 413 (M + 1)+.
2-(3-Methyl-1-phenyl-1H-pyrazol-5-yl)-3H-benzo[f]chromen-3-one (4ab). White solid, 186–188 °C; IR (KBr): 2976, 1732, 1713, 1605, 1495, 1468, 1384, 1049 cm−1; 1H NMR (CDCl3, 500 MHZ) δ ppm: 8.77 (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), 7.77–7.71 (m, 3H), 7.60 (t, J = 7.0 Hz, 1H), 7.50–7.45 (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%; ESI-MS: m/z = 353 (M + 1)+.
2-(3-Methyl-1-(m-tolyl)-1H-pyrazol-5-yl)-3H-benzo[f]chromen-3-one (4ac). White solid, 201–202 °C; IR (KBr): 3120, 1731, 1663, 1600, 1517, 1454, 1397, 1050, 740, 689 cm−1; 1H NMR (CDCl3, 500 MHZ) 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 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%; ESI-MS: 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 solid, 200–201 °C; IR (KBr): 3057, 1760, 1698, 1601, 1500, 1466, 1384, 1034, 778, 725 cm−1; 1H NMR (CDCl3, 500 MHZ) 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 (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%; ESI-MS: 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, 198–200 °C; IR (KBr): 3015, 1732, 1667, 1610, 1512, 1454, 1400, 1075 cm−1; 1H NMR (CDCl3, 500 MHZ) 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%; ESI-MS: 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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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c5ra01677k
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