La(OTf)₃ catalyzed reaction of salicylaldehyde phenylhydrazones with β-ketoesters and activated alkynes: facile approach for the preparation of chromenopyrazolones

Abstract

A facile approach has been developed for the preparation of chromenopyrazolones (5a–o, 7a–k) by the reaction of salicylaldehyde phenylhydrazones (3a–o) with β-ketoesters (4a, 4f–g) and activated alkynes (6a–e) in the presence of La(OTf)₃ with good yields. However, the reaction of salicylaldehyde phenylhydrazones (3a, 3c, 3j–k, 3n) with ethyl 4-chloro-3-oxobutanoate (4e) underwent cyclization with reductive dechlorination and provided the methyl chromenopyrazolones instead of chloromethyl chromenopyrazolones. The present solvent free protocol provided the novel heterocyclic compounds.

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Introduction

Coumarin and its derivatives have been found in many natural products.¹ Coumarin is an important heterocycle and is known for its pharmaceutical and medicinal properties.² Further, coumarin compounds are commercially exploited as optical brighteners and laser dyes.³ On the other hand, chromenopyrazolones are important tricyclic heteroaromatic compounds^4a and benzodiazepine receptor (BZR) ligands. Benzodiazepine receptors are important tools to find out the physiological properties and structural requirements for the recognition site of the receptor. Previously, arylpyrazoloquinolin-4-ones have been reported as benzodiazepine receptors.^4c A series of 1,4-dihydro-1-aryl-3-methylbenzopyrano[3,4-d]-pyrazolo-4-ones and 2,4-dihydro-2-aryl-3-methylbenzopyrano[4,3-c]-pyrazolo-4-ones have been reported by the reaction of arylhydrazones of 3-acetyl-4-hydroxycoumarin.^4b–d These benzopyranopyrazolo-4-ones are identified as BZR receptors. Wang et al.^4e,f reported 3-methyl-1-phenylchromeno[4,3-c]pyrazol-4(1H)-ones by the oxidative cyclization of 3-acylcoumarin hydrazones using CuSO₄·5H₂O. Therefore, benzopyranopyrazolones continue to draw considerable attention from synthetic and medicinal chemists.

β-Ketoesters⁵ are important reagents utilized for the preparation of various biologically important heterocyclic compounds. β-Ketoesters bearing electron withdrawing substituents such as chloro, trichloro and trifluoro groups have the influence in promoting the reactions. As part of our ongoing research on β-ketoesters, we have studied the reactions between salicylaldehydes and β-ketoesters and described below. Condensation of salicylaldehydes and ethyl 4-chloro-3-oxobutanoate in the presence of piperidine provided 2H-chromenes,^6a interim these derivatives were successfully converted to useful heterocyclic compounds.^6b–e

Further, a systematic study has been conducted for the preparation of 1H-benzimidazoles, pyrazolones and pyrazoles by the condensation of ortho-phenylenediamines and phenylhydrazines with ethyl 4-chloro-3-oxobutanoate.^6f Condensation of salicylaldehydes with ethyl 4,4,4-trichloro-3-oxobutanoate in the presence of piperidine provided 2H-chromene-3-carboxylates.^6g Carbonyl compounds with ethyl 4,4,4-trifluoro-3-oxobutanoate provided a series of (E)-α,β-unsaturated esters and ketones.^6h

Activated alkynes⁷ are also an important reagents and have been utilized for the preparation of various natural products, carbocyclic and heterocyclic compounds. As part of our work on activated alkynes, we prepared 2-oxo-2H-chromenylpyrazolecarboxylates by [3 + 2] cycloaddition of 2H-chromenophenylhydrazones with diethyl/dimethyl but-2-ynedioates.⁸ Aforesaid importance of β-ketoesters, activated alkynes and our previous work prompted us to study the reaction of salicylaldehyde phenylhydrazones with β-ketoesters and activated alkynes to prepare novel chromenopyrazolones (Scheme 1).

Scheme 1 Synthesis of chromenopyrazolones 5a–o and 7a–k.

Results and discussion

To optimize the reaction conditions, the reaction was studied by employing a series of catalysts with solvents and under solvent free conditions. In an initial experiment, we conducted the three-component, one-pot reaction of salicylaldehyde (1a, 1 mmol), phenylhydrazine (2a, 1 mmol) and ethyl 3-oxobutanoate (4a, 1 mmol) at 130 °C without any catalyst. The expected compound did not formed; however, salicylaldehyde phenylhydrazone was obtained. Then the reaction was carried out in the presence of La(OTf)₃ (30 mol%)⁹ at 130 °C for 8–10 h. This provided 3-methyl-2-phenylchromeno[4,3-c]pyrazol-4(2H)-one 5a in 20% yield.^4a The structure of the chromenopyrazolone 5a was well characterized by FT-IR, ¹H NMR, ¹³C NMR and HRMS spectroscopies. The three-component, one-pot reaction provided the desired compound 5a in fewer yields. Then, we investigated the reaction of salicylaldehyde phenylhydrazone 3a with ethyl 3-oxobutanoate 4a. Accordingly, salicylaldehyde phenylhydrazone 3a was prepared by the reaction of salicylaldehyde (1a, 1 mmol) and phenylhydrazine (2a, 1 mmol) in acetonitrile at room temperature. The hydrazone 3a (1 mmol) and ethyl 3-oxobutanoate 4a (1.2 mmol) were heated at 130 °C in the presence of La(OTf)₃ (30 mol%, Scheme 2). The reaction was smoothly underwent and provided the chromenopyrazolone 5a in 69% yield.

Scheme 2 Preparation of chromenopyrazolone 5a.

In order to find out the best catalyst to provide target compound 5a, the reaction of 3a (1 mmol) and 4a (1.2 mmol) have been investigated with various catalysts such as protic acids (Table 1, entries 1–2), p-TsOH (entry 3) and Lewis acids (entries 4–14) at 130 °C. La(OTf)₃ provided the compound 5a in better yield when compared to other Lewis acids (entry 13). Lanthanide triflates⁹ are new type of Lewis acids different from typical Lewis acids such as AlCl₃, BF₃, and SnCl₄ etc. La(OTf)₃ is quite stable, highly effective even in aqueous media and reusable catalyst for several important carbon–carbon bond forming reactions.

Table 1 Optimization of reaction condition for the preparation of 5a

Entry	Catalyst	Quantity (equiv.)	Solvent	Time (h)	Yield^e (%)
a 110 °C.b Room temperature.c 130 °C.d Reflux.e Isolated yields.
1	AcOH	2.0	—^a	10	—
2	H2SO4	1.0	—^b	18	—
3	ρ-TsOH	1.0	—^c	24	—
4	AlCl3	1.0	—^c	10	54
5	FeCl3	1.0	—^c	10	57
6	lnCl3	0.3	—^c	10	51
7	SnCl2	0.3	—^c	10	49
8	ZrOCl2·8H2O	0.3	—^c	24	—
9	Cu(OAc)2	1.0	—^c	24	—
10	Sc(OTf)3	0.3	—^c	10	53
11	Bi(OTf)3	0.3	—^c	10	45
12	La(OTf)3	0.2	—^c	10	52
13	La(OTf)3	0.3	—^c	08	69
14	La(OTf)3	0.5	—^c	10	69
15	La(OTf)3	0.3	Toluene^d	24	59
16	La(OTf)3	0.3	DCM^d	24	53
17	La(OTf)3	0.3	Ethanol^d	24	60
18	La(OTf)3	0.3	CH3CN^d	24	48

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Lewis acids such as ZrOCl₂ and Cu(OAc)₂ did not promote the reaction (entry 8–9). Further, we have investigated the effect of the amount of [20 and 50 mol%] La(OTf)₃ at 130 °C. Moderate yield was obtained when less than 30 mol% of the catalyst was used (entry 12). There is no further improvement in the yield with an excess mol% of catalyst (entry 14). Next, the reaction of 3a and 4a was investigated with various solvents (toluene, DCM, C₂H₅OH and CH₃CN) under reflux conditions in the presence of La(OTf)₃ (30 mol%, Table 1, entry 15–18). The results of this study indicated that the conventional heating at 130 °C was more efficient with respect to the reaction time and yield of the product 5a than using organic solvents.

To study the scope and efficiency of this methodology, we prepared various salicylaldehyde phenylhydrazones 3b–o by the reaction of substituted salicylaldehydes (5-methyl 1b, 4-methoxy 1c, 5-fluoro 1d, 5-chloro 1e, 5-bromo 1f, 3,5-dichloro 1g, 3,5-dibromo 1h and 3-bromo-5-chloro 1i) with phenylhydrazine hydrochlorides (4-methoxy 2b, 2-methyl 2c, 4-methyl 2d, 3,4-dimethyl 2e, 4-chloro 2f and 3,4-dichloro 2g). Thus, obtained hydrazones 3b–o were reacted with ethyl 3-oxobutanoate 4a in the presence of La(OTf)₃ at 130 °C to provide corresponding chromenopyrazolones 5b–o (Table 2). The newly prepared compounds 5b–o are well characterized by spectral data (see ESI†). Under these conditions, salicylaldehyde phenylhydrazones such as 2,4-dihydroxy 3p, 2-hydroxy-5-nitro 3q, 4-(benzyloxy)-2-hydroxy 3r and 4-(allyloxy)-2-hydroxy 3s did not provided the corresponding chromenopyrazolones.

Table 2 Preparation of chromenopyrazolones 5a–o

Entry	R^1	R^2	R^3	R^4	R^5	R^6	Compound	Yield^a (%)
a Isolated yields.
1	H	H	H	H	H	H	5a	69
2	H	OCH3	H	H	H	H	5b	62
3	CH3	H	H	H	H	H	5c	64
4	F	H	H	H	H	H	5d	71
5	Cl	H	H	H	H	H	5e	70
6	Br	H	H	H	H	H	5f	71
7	Cl	H	Cl	H	H	H	5g	74
8	Br	H	Br	H	H	H	5h	76
9	Cl	H	Br	H	H	H	5i	79
10	H	H	H	H	H	OCH3	5j	57
11	H	H	H	CH3	H	H	5k	52
12	H	H	H	H	H	CH3	5l	48
13	H	H	H	H	CH3	CH3	5m	57
14	H	H	H	H	H	Cl	5n	50
15	H	H	H	H	Cl	Cl	5o	46

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A plausible mechanism was depicted in Scheme 3. The enol formation of β-ketoesters could significantly catalyze by lanthanide triflates.⁹ The addition reaction between enol of β-ketoesters and salicylaldehyde phenylhydrazone provides the intermediate ethyl 2-((2-hydroxyphenyl)(2-phenylhydrazinyl)methyl)-3-oxobutanoate by the elimination of ethyl alcohol. Further, the La(OTf)₃ co-ordinates between the amine and carbonyl carbon. Finally, intramolecular cyclization and aromatization provides the chromenopyrazolones by the elimination of hydrogen and water.

Scheme 3 Plausible catalytic cycle for the preparation of 5a.

Having achieved the preparation of chromenopyrazolone 5a under conventional method, next, we attempted the reaction of 3a with 4a under microwave conditions. Accordingly, salicylaldehyde phenylhydrazone 3a (1 mmol), ethyl 3-oxobutanoate 4a (1.2 mmol) and La(OTf)₃ (30 mol%) were adsorbed on neutral Al₂O₃ and subjected to microwave irradiation (180 W, Scheme 4). The progress of the reaction was monitored by TLC (16 min). The usual work up and after column chromatography purification compound 5a afforded in 55% yield.

Scheme 4 Microwave assisted preparation of chromenopyrazolone 5a.

Further, we have investigated the electron donating 3b, 3c and withdrawing substitutents 3d–f present on salicylaldehyde moiety of salicylaldehyde phenylhydrazones with 4a under microwave conditions (8–20 min). The chromenopyrazolones 5b (48%), 5c (52%), 5d (64%), 5e (65%) and 5f (64%) were obtained in good to moderate yields. Next, we have investigated the electron donating 3j, 3l and withdrawing substitutents 3n present on phenylhydrazone moiety of salicylaldehyde phenylhydrazones with 4a. However, these reactions did not go smoothly and moreover multiple spots were observed. Therefore, we have chosen the conventional method for the preparation of chromenopyrazolones by the reaction of salicylaldehyde phenylhydrazones with other β-ketoesters and activated alkynes were discussed below.

The reaction of salicylaldehyde phenylhydrazone 3a with various β-ketoesters such as ethyl 3-oxo-3-phenylpropanoate 4b, ethyl 4,4,4-trifluoro-3-oxobutanoate 4c, ethyl 4,4,4-trichloro-3-oxobutanoate 4d, ethyl 4-chloro-3-oxobutanoate 4e, ethyl 2-chloro-3-oxobutanoate 4f, 2-methoxy ethyl 3-oxobutanoate 4g and diethyl malonate 4h in the presence of La(OTf)₃ (30 mol%) at 130 °C (Scheme 5). The β-ketoesters 4e, 4f and 4g facilitated the reaction and provided the chromenopyrazolone 5a in good yield. However, phenyl, trifluoro and trichloro oxobutanoates 4b–d and diethyl malonate 4h did not provided the chromenopyrazolones. Interestingly, the reaction of 3a with ethyl 4-chloro-3-oxobutanoate 4e underwent cyclization with reductive dechlorination and provided 5a.

Scheme 5 Reaction of 3a with β-ketoesters 4b–h.

The cyclization and reductive dechlorination reaction prompted us to investigate further with various salicylaldehyde phenylhydrazones. Accordingly, we have carried out the reaction of various salicylaldehyde phenylhydrazones (3a, 3c, 3j–k, 3n) with ethyl 4-chloro-3-oxobutanoate 4e in the presence of La(OTf)₃ at 130 °C. All these reactions were preceded smoothly and provided the corresponding chromenopyrazolones (5a, 5c, 5j–k, 5n) in good yields (Table 3).

Table 3 Preparation of chromenopyrazolones 5a, 5e, 5j–k, 5n

Entry	R^1	R^2	R^3	R^4	R^5	R^6	Compound	Yield^a (%)
a Isolated yields.
1	H	H	H	H	H	H	5a	67
2	CH3	H	H	H	H	H	5c	61
3	H	H	H	H	H	OCH3	5j	54
4	H	H	H	CH3	H	H	5k	53
5	H	H	H	H	H	Cl	5n	50

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Having achieved the preparation of chromenopyrazolones 5a–o, next, we extended this protocol to investigate 3a with activated alkyne such as diethyl but-2-ynedioate 6a. Accordingly, salicylaldehyde phenylhydrazone 3a and diethyl but-2-ynedioate 6a were heated at 130 °C in the presence of La(OTf)₃ (30 mol%, Scheme 6). The reaction proceeded smoothly and provided ethyl 4-oxo-2-phenyl-2,4-dihydrochromeno[4,3-c]pyrazole-3-carboxylate 7a. The compound 7a is new and well characterized by spectral data.

Scheme 6 Preparation of chromenopyrazole-3-carboxylate 7a.

The result encouraged us to carry out the reaction of salicylaldehyde phenylhydrazones with various activated alkynes 6a–e (Table 4). Accordingly, salicylaldehyde phenylhydrazone 3a reacted with alkynes such as diethyl but-2-ynedioate 6a, dimethyl but-2-ynedioate 6b, ethyl propiolate 6c, ethyl but-2-ynoate 6d and ethyl 3-phenylpropiolate 6e under optimized conditions. All these reactions provided the chromenopyrazole-3-carboxylates 7b–e. Next, we have carried out the reaction of salicylaldehyde phenylhydrazones 3b–c, 3f–g, 3l and 3n with diethyl but-2-ynedioate 6a under optimized conditions provided 7f–k. All these reactions underwent smoothly and provided the corresponding chromenopyrazole-3-carboxylates 7b–k. All the compounds are well characterized by spectral data.

Table 4 Preparation of chromenopyrazole 3-carboxylates 7a–k

Entry	R	R^1	R^2	R^3	Compound	Yield^a (%)
a Isolated yields.
1	H	H	C2H5	CO2C2H5	7a	64
2	H	H	CH3	CO2CH3	7b	65
3	H	H	C2H5	H	7c	68
4	H	H	C2H5	CH3	7d/5a	65
5	H	H	C2H5	Ph	7e	67
6	4-OCH3	H	C2H5	CO2C2H5	7f	51
7	5-CH3	H	C2H5	CO2C2H5	7g	54
8	5-Br	H	C2H5	CO2C2H5	7h	67
9	5-Cl	H	C2H5	CO2C2H5	7i	65
10	H	Cl	C2H5	CO2C2H5	7j	74
11	H	CH3	C2H5	CO2C2H5	7k	77

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Conclusions

In summary, a facile and solvent free method was developed for the preparation of chromenopyrazolones by the reaction of salicylaldehyde phenylhydrazones with β-ketoesters and activated alkynes. The interesting reaction between salicylaldehyde phenylhydrazones and ethyl 4-chloro-3-oxobutanoate underwent cyclization with reductive dechlorination and provided the methyl chromenopyrazolone instead of chloromethyl chromenopyrazolone. This is the first report for the preparation of chromenopyrazolones by the reaction of salicylaldehyde phenylhydrazones with 3-oxobutanoates and activated alkynes. The chromenopyrazolones are an important heterocyclic compounds especially in pharmaceutical and medicinal chemistry.

Experimental section

General

Salicylaldehydes, ethyl 3-oxo-3-phenylpropanoate, ethyl 4,4,4-trifluoro-3-oxobutanoate, ethyl 4,4,4-trichloro-3-oxobutanoate, ethyl 4-chloro-3-oxobutanoate, ethyl 2-chloro-3-oxobutanoate, 2-methoxy ethyl 3-oxobutanoate, diethyl but-2-ynedioate, dimethyl but-2-ynedioate, ethyl propiolate, ethyl but-2-ynoate, ethyl 3-phenylpropiolate, La(OTf)₃, Bi(OTf)₃, Sc(OTf)₃, and InCl₃ were procured from Sigma-Aldrich. Ethyl 3-oxobutanoate, phenylhydrazine hydrochlorides, Lewis acid catalysts and solvents were obtained from local suppliers. All the reactions were monitored by thin layer chromatography (TLC) on pre-coated silica gel 60 F₂₅₄ (mesh); spots were visualized under UV light. Merck silica gel (100–200 mesh) was used for column chromatography. ¹H NMR and ¹³C NMR spectra were recorded on Avance 300, 400 and 500 MHz spectrometer in CDCl₃ using TMS as internal standard. IR spectra were recorded on Nicollet Nexus 670 FT spectrometer. ESI-MS obtained on quarto micro spectrometer. HRMS were measured on Agilent Technologies 6510, Q-TOFLC/MS ESI-Technique. Melting points were determined in open glass capillary tubes on a Stuart melting point apparatus and are uncorrected.

General procedure for the preparation of 2-((2-phenylhydrazono)methyl)phenols (3a–o). Phenylhydrazine (2a, 1 equiv.) was added to a stirred solution of salicylaldehyde (1a, 1 equiv.) in CH₃CN at room temperature. The contents were stirred at the same temperature. The reaction was monitored by TLC, after the completion of the reaction (2 h); the solvent was removed under reduced pressure. The residue was purified by recrystallization with hexane afforded 2-((2-phenylhydrazono)methyl)phenol 3a as colourless solid in 95% yield. The salicylaldehyde phenylhydrazones 3b–o were prepared by the reaction of substituted salicylaldehydes 3a–i with phenylhydrazines 2a–g.

General procedure for the preparation of 3-methyl-2-phenylchromeno-[4,3-c]pyrazol-4(2H)-ones (5a–o). La(OTf)₃ (0.3 equiv.) was added to the 2-((2-phenylhydrazono)methyl)phenol (3a, 1 equiv.) and ethyl 3-oxobutanoate (4a, 1.2 equiv.) at room temperature. The contents were heated to 130 °C for 8–10 h. After completion of the reaction (TLC), the residue was purified by column chromatography by using silica gel (60 : 120, ethyl acetate/hexane 5 : 95) afforded 3-methyl-2-phenylchromeno-[4,3-c]pyrazol-4(2H)-one 5a as colourless solid. The substituted 3-methyl-2-phenylchromeno-[4,3-c]pyrazol-4(2H)-ones 5b–o were prepared by the reaction of 2-((2-phenylhydrazono)methyl)phenols 3a–o with ethyl 3-oxobutanoate 4a under optimized conditions.
3-Methyl-2-phenylchromeno[4,3-c]pyrazol-4(2H)-one (5a). Yield: 69%, 8 h; colorless solid; mp 208–210 °C; FT-IR (KBr): 3059, 1741, 1594, 1485, 1456, 1197, 1041, 754, 700 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 8.12 (dd, J = 7.8, 1.6 Hz, 1H aromatic), 7.61–7.51 (m, 5H, aromatic), 7.48 (ddd, J = 8.7, 7.3, 1.6 Hz, 1H, aromatic), 7.39 (dd, J = 8.3, 0.9 Hz, 1H, aromatic), 7.31 (td, J = 7.6, 1.1 Hz, 1H, aromatic), 2.75 (s, 3H, CH₃) ppm; ¹³C NMR (75 MHz, CDCl₃): δ 158.9, 153.13, 148.70, 144.52, 138.45, 130.42, 129.59, 129.42, 125.60, 124.44, 122.80, 117.55, 115.00, 106.49, 12.07 ppm; MS (ESI): (m/z) 277 [M + H]⁺; HRMS (ESI): (m/z) calcd for C₁₇H₁₃N₂O₂ [M + H]⁺ 277.0971, found: 277.0966.
7-Methoxy-3-methyl-2-phenylchromeno[4,3-c]pyrazol-4(2H)-one (5b). Yield: 62%, 9 h; colorless solid; mp 204–206 °C; FT-IR (KBr): 3074, 2966, 2841, 1744, 1514, 1491, 1250, 1199, 1171, 1043, 975, 759 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 8.00 (d, J = 8.8 Hz, 1H, aromatic), 7.61–7.49 (m, 5H, aromatic), 6.91–6.86 (m, 2H, aromatic), 3.88 (s, 3H, OCH₃), 2.73 (s, 3H, CH₃) ppm; ¹³C NMR (75 MHz, CDCl₃): δ 161.54, 159.10, 154.46, 148.85, 144.39, 138.48, 129.42, 125.57, 123.67, 113.89, 112.03, 107.94, 105.52, 101.89, 55.65, 12.03 ppm; MS (ESI): (m/z) 307 [M + H]⁺; HRMS (ESI): (m/z) calcd for C₁₈H₁₅N₂O₃ [M + H]⁺ 307.1077, found: 307.1075.
3,8-Dimethyl-2-phenylchromeno[4,3-c]pyrazol-4(2H)-one (5c). Yield: 64%, 9 h; colorless solid; mp 197–199 °C; FT-IR (KBr): 2923, 2363, 1740, 1595, 1498, 1199, 1011, 813, 776, 697 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 8.11 (dd, J = 7.8, 1.5 Hz, 1H, aromatic), 7.47 (tt, J = 8.9, 4.5 Hz, 1H, aromatic), 7.43–7.35 (m, 5H, aromatic), 7.32–7.28 (m, 1H, aromatic), 2.72 (s, 3H, CH₃), 2.47 (s, 3H, CH₃) ppm; ¹³C NMR (75 MHz, CDCl₃): δ 159.09, 151.16, 148.72, 144.45, 138.43, 134.14, 131.30, 129.47, 125.58, 122.65, 117.21, 114.47, 106.46, 20.86, 12.06 ppm; MS (ESI): (m/z) 291 [M + H]⁺; HRMS (ESI): (m/z) calcd for C₁₈H₁₅N₂O₂ [M + H]⁺ 291.1128, found: 291.1120.
8-Fluoro-3-methyl-2-phenylchromeno[4,3-c]pyrazol-4(2H)-one (5d). Yield: 71%, 8 h; colorless solid; mp 184–186 °C; FT-IR (KBr): 3448, 1748, 1598, 1570, 1497, 1465, 1398, 1256, 1130, 840, 763, 696 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 7.78 (dd, J = 8.2, 3.0 Hz, 1H, aromatic), 7.63–7.51 (m, 5H, aromatic), 7.36 (dd, J = 9.1, 4.4 Hz, 1H, aromatic), 7.18 (ddd, J = 9.1, 8.0, 3.0 Hz, 1H, aromatic), 2.75 (s, 3H, CH₃) ppm; ¹³C NMR (75 MHz, CDCl₃): δ 160.64, 158.51, 157.41, 149.16, 148.05, 144.74, 138.27, 129.60, 125.53, 119.06, 117.77, 117.44, 116.07, 108.73, 106.32, 12.07 ppm; MS (ESI): (m/z) 295 [M + H]⁺; HRMS (ESI): (m/z) calcd for C₁₇H₁₂FN₂O₂ [M + H]⁺ 295.0877, found: 295.0869.
8-Chloro-3-methyl-2-phenylchromeno[4,3-c]pyrazol-4(2H)-one (5e). Yield: 70%, 8 h; colorless solid; mp 180–182 °C; FT-IR (KBr): 3456, 1740, 1595, 1497, 1460, 1396, 1199, 989, 807, 772 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 8.08 (d, J = 2.5 Hz, 1H, aromatic), 7.62–7.52 (m, 5H, aromatic), 7.41 (dd, J = 8.8, 2.5 Hz, 1H, aromatic), 7.31 (d, J = 8.8 Hz, 1H, aromatic), 2.74 (s, 3H, CH₃) ppm; ¹³C NMR (75 MHz, CDCl₃): δ 158.2, 151.39, 147.58, 144.77, 138.25, 130.36, 129.83, 125.51, 122.42, 118.90, 116.14, 106.31, 12.07 ppm; MS (ESI): (m/z) 311 [M + H]⁺; HRMS (ESI): (m/z) calcd for C₁₇H₁₂N₂O₂Cl [M + H]⁺ 311.0581, found: 311.0580.
8-Bromo-3-methyl-2-phenylchromeno[4,3-c]pyrazol-4(2H)-one (5f). Yield: 71%, 8 h; colorless solid; mp 202–204 °C; FT-IR (KBr): 3061, 2925, 1758, 1592, 1493, 1257, 1199, 1030 983, 810, 762 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 8.25 (d, J = 2.4 Hz, 1H, aromatic), 7.61–7.53 (m, 5H, aromatic), 7.52 (dd, J = 3.5, 2.2 Hz, 1H, aromatic), 7.28–7.26 (m, 1H, aromatic), 2.74 (s, 3H, CH₃) ppm; ¹³C NMR (75 MHz, CDCl₃): δ 158.24, 151.91, 147.50, 144.79, 138.24, 133.18, 129.61, 125.51, 119.24, 117.26, 116.62, 106.35, 12.08 ppm; MS (ESI): (m/z) 355 [M + H]⁺; HRMS (ESI): (m/z) calcd for C₁₇H₁₂N₂O₂Br [M + H]⁺ 355.0076, found: 355.0075.
6,8-Dichloro-3-methyl-2-phenylchromeno[4,3-c]pyrazol-4(2H)-one (5g). Yield: 74%, 8 h; colorless solid; mp 205–207 °C; FT-IR (KBr): 3071, 2923, 1744, 1589, 1552, 1496, 1400, 1001, 862, 767, 693 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 8.01 (d, J = 2.4 Hz, 1H, aromatic), 7.61–7.53 (m, 6H, aromatic), 2.75 (s, 3H, CH₃) ppm; ¹³C NMR (75 MHz, CDCl₃): δ 156.89, 147.33, 145.11, 138.14, 130.50, 129.67, 125.50, 123.23, 120.94, 117.23, 106.23, 12.12 ppm; MS (ESI): (m/z) 345 [M + H]⁺; HRMS (ESI): (m/z) calcd for C₁₇H₁₁N₂O₂Cl₂ [M + H]⁺ 345.0192, found: 345.0190.
6,8-Dibromo-3-methyl-2-phenylchromeno[4,3-c]pyrazol-4(2H)-one (5h). Yield: 76%, 8 h; colorless solid; mp 237–239 °C; FT-IR (KBr): 2924, 1761, 1576, 1545, 1495, 1454, 1395, 1217, 1183, 981, 855, 768 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 8.24–8.12 (m, 1H, aromatic), 7.86–7.79 (m, 1H, aromatic), 7.61–7.52 (m, 5H, aromatic), 2.75 (s, 3H, CH₃) ppm; ¹³C NMR (75 MHz, CDCl₃): δ 145.07, 138.13, 136.08, 129.68, 125.48, 124.61, 117.58, 117.12, 106.28, 12.14 ppm; MS (ESI): (m/z) 433 [M + H]⁺; HRMS (ESI): (m/z) calcd for C₁₇H₁₁N₂O₂Br₂ [M + H]⁺ 432.9181, found: 432.9181.
6-Bromo-8-chloro-3-methyl-2-phenylchromeno[4,3-c]pyrazol-4(2H)-one (5i). Yield: 79%, 7.5 h; colorless solid; mp 202–204 °C; FT-IR (KBr): 3059, 1747, 1580, 1550, 1500, 1482, 1398, 1225, 1190, 1007, 859, 769 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 8.05 (d, J = 2.4 Hz, 1H, aromatic), 7.69 (d, J = 2.4 Hz, 1H, aromatic), 7.60–7.53 (m, 5H, aromatic), 2.75 (s, 3H, CH₃) ppm; ¹³C NMR (75 MHz, CDCl₃): δ 156.92, 148.47, 147.18, 145.06, 138.16, 133.39, 129.97, 129.66, 125.51, 121.58, 117.07, 111.70, 106.22, 12.12 ppm; MS (ESI): (m/z) 389 [M + H]⁺; HRMS (ESI): (m/z) calcd for C₁₇H₁₁N₂O₂BrCl [M + H]⁺ 388.9687, found: 388.9679.
2-(4-Methoxyphenyl)-3-methylchromeno[4,3-c]pyrazol-4(2H)-one (5j). Yield: 57%, 8.5 h; colorless solid; mp 211–213 °C; FT-IR (KBr): 2927, 1740, 1624, 1595, 1501, 1274, 1146, 1117, 1028, 975, 773 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 8.10 (d, J = 7.8 Hz, 1H, aromatic), 7.50–7.41 (m, 3H, aromatic), 7.38 (d, J = 8.3 Hz, 1H, aromatic), 7.29 (dd, J = 13.8, 6.2 Hz, 1H, aromatic), 7.09–7.03 (m, 2H, aromatic), 3.90 (s, 3H, OCH₃), 2.70 (s, 3H, CH₃) ppm; ¹³C NMR (75 MHz, CDCl₃): δ 160.22, 158.95, 153.08, 148.45, 144.53, 131.30, 130.33, 126.97, 124.41, 122.75, 117.52, 115.03, 114.68, 106.15, 55.72, 11.97 ppm; MS (ESI): (m/z) 307 [M + H]⁺; HRMS (ESI): (m/z) calcd for C₁₈H₁₅N₂O₃ [M + H]⁺ 307.1077, found: 307.1074.
3-Methyl-2-o-tolylchromeno[4,3-c]pyrazol-4(2H)-one (5k). Yield: 52%, 8.5 h; colorless solid; mp 161–163 °C; FT-IR (KBr): 3061, 2927, 1729, 1593, 1485, 1502, 1322, 1195, 1168, 1039, 975, 756 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 8.09 (dd, J = 7.8, 1.6 Hz, 1H, aromatic), 7.48 (ddt, J = 8.8, 7.5, 1.6 Hz, 2H, aromatic), 7.44–7.37 (m, 3H, aromatic), 7.33–7.28 (m, 2H, aromatic), 2.52 (s, 3H, CH₃), 2.11 (s, 3H, CH₃) ppm; ¹³C NMR (75 MHz, CDCl₃): δ 158.96, 153.11, 148.68, 145.38, 137.16, 135.72, 131.48, 130.43, 127.42, 127.13, 124.44, 122.77, 117.56, 115.08, 17.28, 11.25 ppm; MS (ESI): (m/z) 291 [M + H]⁺; HRMS (ESI): (m/z) calcd for C₁₈H₁₅N₂O₂ [M + H]⁺ 291.1128, found 291.1120.
3-Methyl-2-p-tolylchromeno[4,3-c]pyrazol-4(2H)-one (5l). Yield: 48%, 8 h; colorless solid; mp 209–211 °C; FT-IR (KBr): 2921, 1735, 1593, 1511, 1486, 1450, 1396, 1325, 1199, 1041, 975, 825, 765 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 8.11 (dd, J = 7.8, 1.5 Hz, 1H, aromatic), 7.49–7.44 (m, 1H, aromatic), 7.43–7.35 (m, 5H, aromatic), 7.32–7.27 (m, 1H, aromatic), 2.72 (s, 3H, CH₃), 2.47 (s, 3H, CH₃) ppm; ¹³C NMR (75 MHz, CDCl₃): δ 158.93, 153.06, 148.50, 144.43, 139.6, 135.91, 130.21, 125.38, 124.39, 122.76, 117.50, 115.01, 106.27, 21.29, 12.03 ppm; MS (ESI): (m/z) 291 [M + H]⁺; HRMS (ESI): (m/z) calcd for C₁₈H₁₅N₂O₂ [M + H]⁺ 291.1128, found: 291.1123.
2-(3,4-Dimethylphenyl)-3-methylchromeno[4,3-c]pyrazol-4(2H)-one (5m). Yield: 57%, 8 h; colorless solid; mp 158–160 °C; FT-IR (KBr): 3075, 2922, 1737, 1595, 1501, 457, 1383, 1197, 1154, 820, 746 cm⁻¹; ¹H NMR (300 MHz, CDCl₃); δ 8.11 (dd, J = 7.7, 1.4 Hz, 1H, aromatic), 7.52–7.43 (m, 1H, aromatic), 7.38 (d, J = 7.5 Hz, 1H, aromatic), 7.32–7.21 (m, 4H, aromatic), 2.71 (s, 3H, CH₃), 2.36 (s, 6H, 2CH₃) ppm; ¹³C NMR (75 MHz, CDCl₃): δ 159.04, 153.09, 144.43, 136.10, 130.43, 130.30, 126.62, 122.79, 117.52, 115.08, 106.19, 19.93, 19.63, 12.25 ppm; MS (ESI): (m/z) 305 [M + H]⁺; HRMS (ESI): (m/z) calcd for C₁₉H₁₇N₂O₂ [M + H]⁺ 305.1284, found: 305.1277.
2-(4-Chlorophenyl)-3-methylchromeno[4,3-c]pyrazol-4(2H)-one (5n). Yield: 50%, 9 h; colorless solid; mp 205–207 °C; FT-IR (KBr): 3074, 2921, 1745, 1597, 1495, 1448, 1393, 1198, 1039, 829, 748 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 8.10 (dd, J = 7.8, 1.5 Hz, 1H, aromatic), 7.58–7.54 (m, 2H, aromatic), 7.53–7.47 (m, 3H, aromatic), 7.41–7.37 (m, 1H, aromatic), 7.35–7.29 (m, 1H, aromatic), 2.75 (s, 3H, CH₃) ppm; ¹³C NMR (75 MHz, CDCl₃): δ 158.76, 153.13, 148.89, 144.56, 136.93, 135.40, 130.61, 129.81, 126.77, 124.52, 122.80, 117.60, 114.80, 106.74, 12.10 ppm; MS (ESI): (m/z) 311 [M + H]⁺; HRMS (ESI): (m/z) calcd for C₁₇H₁₂N₂O₂Cl [M + H]⁺ 311.0581, found: 311.0578.
2-(3,4-Dichlorophenyl)-3-methylchromeno[4,3-c]pyrazol-4(2H)-one (5o). Yield: 46%, 10 h; colorless solid; mp 171–173 °C; FT-IR (KBr): 3069, 2924, 2854, 1745, 1595, 1566, 1482, 1320, 1196, 1036, 975, 754 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 8.07 (dd, J = 7.8, 1.6 Hz, 1H, aromatic), 7.65 (d, J = 2.0 Hz, 1H, aromatic), 7.51–7.46 (m, 3H, aromatic), 7.39 (dd, J = 8.4, 1.0 Hz, 1H, aromatic), 7.33–7.29 (m, 1H, aromatic), 2.59 (s, 3H, CH₃) ppm; ¹³C NMR (75 MHz, CDCl₃): δ 158.6, 153.19, 146.60, 137.25, 134.61, 133.12, 130.64, 130.30, 128.48, 124.54, 122.88, 117.63, 114.74, 106.10, 11.26 ppm; MS (ESI): (m/z) 345 [M + H]⁺; HRMS (ESI): (m/z) calcd for C₁₇H₁₁N₂O₂Cl₂ [M + H]⁺ 345.0192, found: 345.0190.

General procedure for the preparation of chromenopyrazolones (5a, 5c, 5j–k, 5n) by the reaction of salicylaldehyde phenylhydrazones (3a, 3c, 3j–k, 3n) with ethyl 4-chloro-3-oxobutanoate (4e). La(OTf)₃ (0.3 equiv.) was added to the salicylaldehyde phenylhydrazones (3a, 3c, 3j–k, 3n, 1 equiv.) and ethyl 4-chloro-3-oxobutanoate (4e, 1.2 equiv.) at room temperature. The contents were heated to 130 °C for 8–10 h. After completion of the reaction (TLC), the residue was purified by column chromatography by using silica gel (60 : 120, ethyl acetate/hexane 5 : 95) and afforded chromenopyrazolones (5a, 5c, 5j–k, 5n). The compounds are well characterised by spectral data and these compounds were compared with the compounds presented in above section.

General procedure for the preparation of ethyl 4-oxo-2-phenyl-2,4-dihydrochromeno[4,3-c]pyrazole-3-carboxylates (7a–k). La(OTf)₃ (0.3 equiv.) was added to the 2-((2-phenylhydrazono)methyl)phenol (3a, 1 equiv.) and diethyl but-2-ynedioate (6a, 1.2 equiv.) at room temperature. The contents were heated at 130 °C for 7–8 h. After completion of the reaction (TLC), the residue was purified by column chromatography by using silica gel (60 : 120, ethyl acetate/hexane 5 : 95) and afforded ethyl 4-oxo-2-phenyl-2,4-dihydrochromeno[4,3-c]pyrazole-3-carboxylate 7a as colourless solid. The substituted ethyl 4-oxo-2-phenyl-2,4-dihydrochromeno[4,3-c]pyrazole-3-carboxylates 7b–k were prepared by the reaction of 2-((2-phenylhydrazono)methyl)phenols 3a–c, 3f–g, 3l and 3n with activated alkynes 6a–e under optimized conditions. The spectral data for 7a–k were depicted below.
Ethyl 4-oxo-2-phenyl-2,4-dihydrochromeno[4,3-c]pyrazole-3-carboxylate (7a). Yield: 64%, 7 h; colorless solid; mp 139–141 °C; FT-IR (KBr): 3431, 3116, 2981, 1762, 1722, 1620, 1594, 1560, 1496, 1448, 1320, 1241, 1138, 1095, 1039, 974, 759 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ 8.15 (dd, J = 7.8, 1.5 Hz, 1H, aromatic), 7.61–7.51 (m, 6H, aromatic), 7.41 (d, J = 7.6 Hz, 1H, aromatic), 7.36–7.31 (m, 1H, aromatic), 4.41 (q, J = 7.1 Hz, 2H, CH₂), 1.27 (t, J = 7.1 Hz, 3H, CH₃); ¹³C NMR (100 MHz, CDCl₃): δ 158.87, 156.05, 153.03, 138.99, 136.26, 130.99, 129.81, 129.36, 124.85, 124.63, 122.94, 117.52, 114.01, 63.11, 13.70 ppm; MS (ESI): (m/z) 357 [M + Na]⁺; HRMS (ESI): (m/z) calcd for C₁₉H₁₄N₂NaO₄ [M + Na]⁺ 357.0846, found: 357.0829.
Methyl 4-oxo-2-phenyl-2,4-dihydrochromeno[4,3-c]pyrazole-3-carboxylate (7b). Yield: 65%, 7 h; colorless solid; mp 143–145 °C; FT-IR (KBr): 3439, 3060, 1758, 1723, 1618, 1592, 1557, 1496, 1452, 1323, 1237, 1140, 1094, 1042, 896, 761 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ 8.16 (dd, J = 7.8, 1.5 Hz, 1H, aromatic), 7.61–7.49 (m, 6H, aromatic), 7.41 (d, J = 7.6 Hz, 1H, aromatic), 7.37–7.31 (m, 1H, aromatic), 3.95 (s, 3H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ 159.46, 156.08, 138.94, 135.77, 131.05, 129.86, 129.42, 124.72, 122.97, 117.54, 113.98, 53.61 ppm; MS (ESI): (m/z) 321 [M + H]⁺; HRMS (ESI): (m/z) calcd for C₁₈H₁₃N₂O₄ [M + H]⁺ 321.087, found: 321.0863.
2-Phenylchromeno[4,3-c]pyrazol-4(2H)-one (7c). Yield: 68%, 8 h; colorless solid; mp 207–209 °C; FT-IR (KBr): 3349, 3116, 2924, 1731, 1620, 1593, 1561, 1504, 1461, 1428, 1281, 1240, 1188, 1104, 1041, 977, 756 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ 8.69 (s, 1H, hetero aromatic), 8.19 (dd, J = 7.8, 1.6 Hz, 1H, aromatic), 7.87–7.82 (m, 2H, aromatic), 7.60–7.43 (m, 4H, aromatic), 7.41 (dd, J = 8.3, 1.0 Hz, 1H, aromatic), 7.36 (td, J = 7.6, 1.1 Hz, 1H, aromatic) ppm; ¹³C NMR (125 MHz, CDCl₃): δ 157.87, 153.07, 149.91, 139.18, 130.67, 129.82, 129.45, 128.59, 124.60, 122.95, 120.39, 117.63, 114.60, 109.43 ppm; MS (ESI): (m/z) 263 [M + H]⁺; HRMS (ESI): (m/z) calcd for C₁₆H₁₁N₂O₂ [M + H]⁺ 263.0815, found: 263.0819.
3-Methyl-2-phenylchromeno[4,3-c]pyrazol-4(2H)-one (7d). Yield: 65%, 8 h; colorless solid; mp 208–210 °C; FT-IR (KBr): 3059, 1741, 1594, 1485, 1456, 1197, 1041, 754, 700 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 8.12 (dd, J = 7.8, 1.6 Hz, 1H aromatic), 7.61–7.51 (m, 5H, aromatic), 7.48 (ddd, J = 8.7, 7.3, 1.6 Hz, 1H, aromatic), 7.39 (dd, J = 8.3, 0.9 Hz, 1H, aromatic), 7.31 (td, J = 7.6, 1.1 Hz, 1H, aromatic), 2.75 (s, 3H, CH₃) ppm; ¹³C NMR (75 MHz, CDCl₃): δ 158.9, 153.13, 148.70, 144.52, 138.45, 130.42, 129.59, 129.42, 125.60, 124.44, 122.80, 117.55, 115.00, 106.49, 12.07 ppm; MS (ESI): (m/z) 277 [M + H]⁺; HRMS (ESI): (m/z) calcd for C₁₇H₁₃N₂O₂ [M + H]⁺ 277.0971, found: 277.0966.
2,3-Diphenylchromeno[4,3-c]pyrazol-4(2H)-one (7e). Yield: 67%, 8 h; colorless solid; mp 228–230 °C; FT-IR (KBr); 3453, 3063, 1734, 1590, 1554, 1493, 1466, 1387, 1331, 1269, 1228, 1199, 1123, 1060, 973, 746 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ 8.19 (d, J = 7.7 Hz, 1H, aromatic), 7.52–7.30 (m, 13H, aromatic) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 157.75, 152.98, 149.18, 146.09, 139.03, 130.49, 129.91, 129.19, 128.81, 128.36, 126.94, 125.83, 124.36, 122.78, 117.39, 114.72, 106.04 ppm; MS (ESI): (m/z): 339 [M + H]⁺; HRMS (ESI): (m/z) calcd for C₂₂H₁₅N₂O₂ [M + H]⁺ 339.1128, found: 339.1124.
Ethyl 7-methoxy-4-oxo-2-phenyl-2,4-dihydrochromeno[4,3-c]pyrazole-3-carboxylate (7f). Yield: 51%, 8 h; colorless solid; mp 188–190 °C; FT-IR (KBr): 3428, 2922, 2852, 1758, 1720, 1627, 1594, 1498, 1462, 1437, 1319, 1266, 1206, 1143, 1031, 982, 772 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 8.03 (d, J = 9.3 Hz, 1H, aromatic), 7.54 (ddd, J = 11.7, 5.1, 2.6 Hz, 5H, aromatic), 6.91 (dd, J = 4.5, 2.3 Hz, 2H, aromatic), 4.40 (q, J = 7.1 Hz, 2H, CH₂), 3.89 (s, 3H, OCH₃), 1.27 (t, J = 7.1 Hz, 3H, CH₃) ppm; ¹³C NMR (125 MHz, CDCl₃): δ 161.98, 158.95, 156.32, 54.46, 149.25, 139.05, 136.20, 135.21, 129.71, 129.34, 124.85, 123.85, 112.40, 106.94, 101.77, 63.06, 55.69, 13.71 ppm; MS (ESI): (m/z) 387 [M + Na]⁺; HRMS (ESI): (m/z) calcd for C₂₀H₁₆N₂NaO₂ [M + Na]⁺ 387.0951, found: 387.0937.
Ethyl 8-methyl-4-oxo-2-phenyl-2,4-dihydrochromeno[4,3-c]pyrazole-3-carboxylate (7g). Yield: 54%, 8 h; colorless solid; mp 160–162 °C; FT-IR (KBr): 3442, 2923, 2852, 1735, 1627, 1596, 1500, 1461, 1393, 1306, 1230, 1185, 1124, 1016, 913, 757 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 7.95 (s, 1H, aromatic), 7.58–7.53 (m, 5H, aromatic), 7.30 (d, J = 3.7 Hz, 2H, aromatic), 4.40 (q, J = 7.1 Hz, 2H, CH₂), 2.44 (s, 3H, CH₃), 1.27 (t, J = 7.1 Hz, 3H, CH₃) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 158.92, 156.25, 151.14, 149.12, 139.02, 134.42, 131.90, 129.77, 129.35, 124.84, 122.79, 120.41, 117.22, 113.55, 108.21, 63.10, 20.83, 13.71 ppm; MS (ESI): (m/z) 349 [M + H]⁺; HRMS (ESI): (m/z) calcd for C₂₀H₁₇N₂O₄ [M + H]⁺ 349.1183, found: 349.1179.
Ethyl 8-bromo-4-oxo-2-phenyl-2,4-dihydrochromeno[4,3-c]pyrazole-3-carboxylate (7h). Yield: 67%, 7.5 h; colorless solid; mp 182–184 °C; FT-IR (KBr): 3429, 2325, 2854, 1724, 1355, 1598, 1551, 1495, 1463, 1371, 1318, 1276, 1243, 1181, 1099, 1033, 984, 757 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ 8.30 (d, J = 2.3 Hz, 1H, aromatic), 7.62–7.58 (m, 1H, aromatic), 7.56 (m, 5H, aromatic), 7.29 (d, J = 8.9 Hz, 1H, aromatic), 4.43 (q, J = 7.1 Hz, 2H, CH₂), 1.28 (t, J = 7.1 Hz, 3H, CH₃) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 158.64, 155.42, 151.89, 147.88, 138.85, 136.47, 133.82, 129.99, 129.42, 125.66, 124.80, 120.42, 119.26, 117.48, 115.69, 63.24, 13.71 ppm; MS (ESI): (m/z) 435 [M + Na]⁺; HRMS (ESI): (m/z) calcd for C₁₉H₁₃BrN₂NaO₄ [M + Na]⁺ 434.9951, found: 434.9954.
Ethyl 8-chloro-4-oxo-2-phenyl-2,4-dihydrochromeno[4,3-c]pyrazole-3-carboxylate (7i). Yield: 65%, 7.5 h; colorless solid; mp 192–194 °C; FT-IR (KBr): 3103, 3061, 2923, 2852, 1780, 1737, 1618, 1596, 1553, 1495, 1433, 1371, 1317, 1249, 1188, 1107, 1018, 985, 758 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 8.14 (d, J = 2.5 Hz, 1H, aromatic), 7.56 (d, J = 1.9 Hz, 5H, aromatic), 7.46 (dt, J = 6.2, 3.1 Hz, 1H, aromatic), 7.35 (d, J = 8.9 Hz, 1H, aromatic), 4.41 (q, J = 7.1 Hz, 2H, CH₃), 1.27 (t, J = 7.1 Hz, 3H, CH₃) ppm; ¹³C NMR (125 MHz, CDCl₃): δ 158.65, 155.45, 151.38, 148.00, 138.84, 136.46, 130.96, 130.12, 129.97, 129.41, 124.79, 122.64, 118.94, 115.24, 108.08, 63.23, 13.71 ppm; MS (ESI): (m/z) 391 [M + Na]⁺; HRMS (ESI): (m/z) calcd for C₁₉H₁₃ClN₂NaO₄ [M + H]⁺ 391.0456, found: 391.0472.
Ethyl 2-(4-chlorophenyl)-4-oxo-2,4-dihydrochromeno[4,3-c]pyrazole-3-carboxylate (7j). Yield: 74%, 7.5 h; colorless solid; mp 170–172 °C; FT-IR (KBr): 3078, 2924, 1764, 1720, 1619, 1554, 1495, 1468, 1443, 1321, 1276, 1242, 1191, 1138, 1093, 1036, 979 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 8.12 (dd, J = 7.8, 1.4 Hz, 1H, aromatic), 7.55–7.50 (m, 5H, aromatic), 7.43–7.37 (m, 1H, aromatic), 7.36–7.31 (m, 1H, aromatic), 4.43 (q, J = 7.1 Hz, 2H, CH₂), 1.33 (t, J = 7.1 Hz, 3H, CH₃) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 158.73, 155.82, 153.01, 149.17, 137.42, 36.20, 135.86, 131.13, 129.53, 126.16, 124.67, 122.92, 117.53, 113.80, 108.38, 63.29, 13.77 ppm; MS (ESI): (m/z) 391 [M + Na]⁺; HRMS (ESI): (m/z) calcd for C₁₉H₁₃ClN₂NaO₄ [M + Na]⁺ 391.0456, found: 391.0469.
Ethyl 4-oxo-2-(p-tolyl)-2,4-dihydrochromeno[4,3-c]pyrazole-3-carboxylate (7k). Yield: 77%, 7.5 h; colorless solid; mp 148–150 °C; FT-IR (KBr): 3124, 2386, 2320, 1740, 1726, 1618, 1562, 1509, 1448, 1393, 1362, 1323, 1236, 1188, 1086, 1035, 979, 772 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ 8.14 (dd, J = 7.8, 1.5 Hz, 1H, aromatic), 7.71 (d, J = 8.5 Hz, 1H, aromatic), 7.52–7.48 (m, 1H, aromatic), 7.44 (s, 1H, aromatic), 7.42–7.38 (m, 1H, aromatic), 7.35–7.32 (m, 3H, aromatic), 4.41 (q, J = 7.1 Hz, 2H, CH₂), 2.45 (s, 3H, CH₃), 1.29 (t, J = 7.1 Hz, 3H, CH₃) ppm; ¹³C NMR (125 MHz, CDCl₃): δ 158.95, 156.02, 152.94, 148.80, 140.03, 136.50, 36.07, 130.84, 130.25, 129.84, 124.55, 122.87, 120.20, 117.42, 114.01, 63.03, 21.21, 13.71 ppm; MS (ESI): (m/z) 371 [M + Na]⁺; HRMS (ESI): (m/z) calcd for C₂₀H₁₆N₂NaO₄ [M + Na]⁺ 371.1002, found: 371.0991.

Acknowledgements

The authors thank Dr. S. Chandrasekhar, Director, CSIR-IICT for constant encouragement. B. China Raju acknowledges SERB-DST, New Delhi for financial support (SB/EMEQ-301/2013).

Notes and references

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c6ra21717f

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