Reactions of 3H-furan-2-ones and 2H-chromen-2-ones with pyrazole-3(5)-diazonium salts

Inna D. Mokhonova; Evgenij A. Maksimov; Irina V. Ledenyona; Alevtina Y. Yegorova; Khidmet S. Shikhaliev

doi:10.1515/hc-2017-0192

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Reactions of 3H-furan-2-ones and 2H-chromen-2-ones with pyrazole-3(5)-diazonium salts

Inna D. Mokhonova , Evgenij A. Maksimov , Irina V. Ledenyona , Alevtina Y. Yegorova and Khidmet S. Shikhaliev

Published/Copyright: July 13, 2018

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From the journal Heterocyclic Communications Volume 24 Issue 4

Abstract

Derivatives of the new heterocyclic system, 6H-chromeno[4,3-e]pyrazolo[5,1-c][1,2,4]triazin-6-one, were obtained by the reaction of pyrazole-3(5)-diazonium salts with 4-hydroxy-2H-chromen-2-one. Similar reactions with 5-phenyl-3H-furan-2-one followed by intramolecular heterocyclization furnished 6-(4-halophenyl)-7-alkyl-2-phenylfuro[2,3-e]pyrazolo[5,1-c][1,2,4]triazines.

Keywords: 3H-furan-2-one; azo compounds; cyclocondensation; heterocyclic; intramolecular; pyrazolo[5,1-c][1,2,4]triazine

Introduction

The structure and stability of pyrazole-3(5)-diazonium salts are the subject of many research reports [1], [2], [3], [4], [5], [6], [7], [8]. However, the reactions of pyrazole-diazonium salts with heterocycles remain poorly studied [9]. The ability of the reaction products to undergo further cyclizations has not been sufficiently investigated. At the same time, the use of methylene-active compounds of heterocyclic series as the azo component in reactions with pyrazole-3(5)-diazonium salts opens up wide opportunities for the synthesis of new promising biologically active polyheterocyclic systems [10], [11], [12], [13]. Previously, successful attempts have been made to react pyrazole-3(5)-diazonium salts with several methylene-active heterocyclic compounds including barbituric and thiobarbituric acids, isochromane-1,3-diones, as well as the derivatives of pyridine-2,4-dione, pyran-2,4-dione and pyrimidine-2,4-dione [14], [15], [16]. The purpose of this work was to synthesize derivatives of substituted pyrazolotriazines by introducing into their structure oxygen-containing six- and five-membered rings.

Results and discussion

In continuation of our previous research, the pyrazole-3(5)-diazonium salt 1a–c was allowed to react with 4-hydroxy-2H-chromen-2-one (2). This reaction furnished colored azo compounds 3a–c or hydrazones 3′a–′c [17], [18] that were difficult to isolate. Heating under reflux of 3a–c or 3′a–′c under acid catalysis led to intramolecular cyclocondensation of these compounds due to attack of the endo-cyclic nitrogen atom of pyrazole at the cyclic ketone group. Based on proton nuclear magnetic resonance (¹H NMR) spectroscopic data, the products were 6H-chromeno[4,3-e]pyrazolo[5,1-c][1,2,4]triazin-6-ones 4a–c. These products were obtained in 66–85% yields. Their ¹H NMR spectra show no signals of the NH protons of the pyrazole and hydrazone fragments within the typical range of 12–13 ppm, as well as no proton signals of the hydroxyl groups of the salicylic fragment [19], [20].

In contrast to the reaction of Scheme 1, the hydrazones 6b–d, obtained by coupling of pyrazole-3(5)-diazonium salts 1b–d with 5-phenyl-3H-furan-2-one (5), were isolated and characterized (Scheme 2). Under acid catalysis, compounds 6b–d underwent intramolecular cyclocondensation to new derivatives of phenylfuro[2,3-e]pyrazolo[5,1-c][1,2,4]triazines 7b–d. The reaction was carried out under reflux in acetic acid for 6 h.

Scheme 1

Scheme 2

In summary, the reactions of readily available pyrazole-3(5)-diazonium salts with heterocyclic azo components are convenient ways for obtaining new derivatives of pyrazolo[5,1-c][1,2,4]triazine and polyheterocyclic ensembles with their fragments.

Experimental

¹H NMR spectra were recorded on a Varian 400 and a Bruker DRX-500 (400 and 500 MHz, respectively) spectrometers at 20°C in hexadeuterated dimethylsulfoxide (DMSO-d₆) in the presence of tetramethylsilane (TMS) as internal standard. Elemental analysis was carried out on a Carlo Erba NA 1500 and a VarioMicroCube devices. Melting points were measured on a Stuart SMP30 instrument. Qualitative analysis of the reaction mixtures was carried out using thin layer chromatography (TLC) on silica gel 60 F245, silufol UV-245 and alugram N/UN₂₄₅ plates, eluting with hexane, ethyl acetate and chloroform or their mixtures. Chromatograms were visualized under UV light or exposure to iodine vapor.

General synthesis of compounds 4a–c, 6b–d and 7b–d

A solution of 10 mmol of a substituted 5-aminopyrazole (10 mmol) in water (15 mL) and hydrochloric acid (30 mL, d=1.19 g/cm³) was stirred at 0°C and treated with an aqueous solution of NaNO₂ (10 mmol, 10%). After stirring for 10 min at 0°C, the solution of the resultant pyrazole-3(5)-diazonium salt 1a–d was transferred in portions to a mixture containing compound 2 or 5 (10 mmol), ethanol (10 mL) and a saturated aqueous solution of sodium acetate (7 mL). The mixture was stirred for 4–5 h and then the precipitate of 3a–c or 6b–d was filtered off, washed with water and dried at room temperature. A solution of each individual compound in acetic acid (50 mL) was heated under reflux for 20 min for product 4a–c and for 6 h for product 7b–d. The solution was cooled slowly, and the resultant crystalline precipitate was filtered off, washed with cold 2-propanol (50 mL), dried and crystallized from acetic acid.

3-Phenyl-6H-chromeno[4,3-e]pyrazolo[5,1-c][1,2,4]triazin-6-one (4a)

This compound was obtained from 1a; red crystals; yield 66%; mp 260–262°C; ¹H NMR: δ 7.41 (t, 1H, ³J=7.4 Hz), 7.56–7.64 (m, 4H), 7.92–7.97 (m, 1H), 8.36 (d, 2H, ³J=7.6 Hz), 9.23 (s, 1H), 9.81 (d, 1H, ³J=8.3 Hz). Anal. Calcd for C₁₈H₁₀N₄O₂: C, 68.79; H, 3.12; N, 17.83. Found: C, 68.85; H, 3.12; N, 17.90.

3-(4-Chlorophenyl)-2-methyl-6H-chromeno[4,3-e]pyrazolo[5,1-c][1,2,4]triazin-6-one (4b)

This compound was obtained from 1b; red-orange crystals; yield 82%; mp 270–272°C; ¹H NMR: δ 1.29 (s, 3H), 7.51 (t, 1H, ³J=7.5 Hz), 7.62–7.67 (m, 2H), 7.87–7.98 (m, 5H, ³J=7.6 Hz), 9.79 (d, 1H, ³J=8.1 Hz). Anal. Calcd for C₁₉H₁₁ClN₄O₂: C, 62.91; H, 3.06; N, 15.44. Found: C, 62.85; H, 3.06; N, 15.48.

3-(4-Bromophenyl)-2-ethyl-6H-chromeno[4,3-e]pyrazolo[5,1-c][1,2,4]triazin-6-one (4c)

This compound was obtained from 1c; orange crystals; yield 75%; mp 265–267°C; ¹H NMR: δ 1.27 (t, 3H), 2.77 (dd, 2H), 7.13–7.88 (m, 7H), 9.56–9.70 (m, 1H), the sample is paramagnetic. Anal. Calcd for C₂₀H₁₃BrN₄O₃: C, 57.02; H, 3.11; N, 13.30. Found: C, 57.10; H, 3.15; N, 13.55.

5-Phenyl-3-(2-(4-(4-chlorophenyl)-3-methyl-1H-pyralol-5-yl)hydrazono)-3H-furan-2-one (6b)

This compound was obtained from 1b; green-yellow crystals; yield 76%; mp 129–131°C; ¹H NMR: δ 1.25 (s, 3H), 6.20 (s, 1H), 7.80–7.89 (dd, 4H, ³J=7.8 Hz), 7.25–7.48 (m, 5H, ³J=7.4 Hz), 8.70 (s, 1H), 11.80 (s, 1H). Anal. Calcd for C₂₀H₁₅ClN₄O₂: C, 63.49; H, 3.97; N, 14.82. Found: C, 63.12; H, 3.97; N, 14.95. N, 14.82.

5-Phenyl-3-(2-(4-(4-bromophenyl)-3-ethyl-1H-pyralol-5-yl)hydrazono)-3H-furan-2-one (6c)

This compound was obtained from 1c; orange crystals; yield 73%; mp 140–142°C; ¹H NMR: δ 1.25 (t, 3H), 2.65 (dd, 2H), 6.51 (s, 1H), 7.26–7.50 (m, 5H, ³J=7.4 Hz), 7.76–7.89 (m, 5H, ³J=7.8 Hz), 8.77 (s, 1H), 11.94 (s, 1H). Anal. Calcd for C₂₁H₁₇BrN₄O₂: C, 57.67; H, 3.89; N, 12.81. Found: C, 57.61; H, 3.89; N, 12.92.

5-Phenyl-3-(2-(4-(4-fluorophenyl)-1H-pyrazol-5-yl)hydrazono)-3H-furan-2-one (6d)

This compound was obtained from 1d; red-orange crystals; yield 68%; mp 205–207°C; ¹H NMR: δ 6.23 (s, 1H), 7.30–7.37 (m, 4H, ³J=7.3 Hz), 7.53–7.70 (m, 4H, ³J=7.6 Hz), 7.89 (m, 2H, ³J=7.8 Hz), 8.71 (s, 1H), 11.90 (s, 1H). Anal. Calcd for C₁₉H₁₃FN₄O₂: C, 65.52; H, 3.74; N, 16.09. Found: C, 65.49; H, 3.74; N, 16.12.

6-(4-Chlorophenyl)-7-methyl-2-phenylfuro[2,3-e]pyrazolo[5,1-c][1,2,4]triazine (7b)

This compound was obtained from 9g; brown crystals; yield 73%; mp 101–103°C; ¹H NMR: δ 2.15 (s, 3H), 7.35–7.46 (m, 5H, ³J=7.4 Hz), 7.80–8.06 (m, 4H, ³J=7.9 Hz), 8.45 (s, 1H). Anal. Calcd for C₂₀H₁₃ClN₄O: C, 66.67; H, 3.61; N, 15.56. Found: C, 66.79; H, 3.61; N, 15.62.

6-(4-Bromophenyl)-7-ethyl-2-phenylfuro[2,3-e]pyrazolo[5,1-c][1,2,4]triazine (7c)

This compound was obtained from 9h; brown crystals; yield 75%; mp 95–97°C; ¹H NMR: δ 1.15 (t, 3H), 1.75 (m, 2H), 7.11–7.53 (m, 5H, ³J=7.3 Hz), 7.85–8.19 (m, 4H, ³J=8.1 Hz), 8.67 (s, 1H). Anal. Calcd for C₂₁H₁₅BrN₄O: C, 60.14; H, 3.58; N, 13.37. Found: C, 60.29; H, 3.58; N, 13.12.

6-(4-Fluorophenyl)-2-phenylfuro[2,3-e]pyrazolo[5,1-c][1,2,4]triazine (7d)

This compound was obtained from 9f; brown crystals; yield 77%; mp 105–107°C; ¹H NMR: δ 6.52 (s, 1H), 7.10–7.50 (m, 5H, ³J=7.3 Hz), 8.12–8.26 (m, 5H, ³J=8.2 Hz), 8.60 (s, 1H). Anal. Calcd for C₁₉H₁₁FN₄O: C, 69.09; H, 3.33; N, 16.97. Found: C, 69.21; H, 3.33; N, 16.52.

Funding source: Russian Foundation for Basic Research

Award Identifier / Grant number: 16-03-00530

Funding statement: This work was supported by the Russian Foundation for Basic Research, grant 16-03-00530 (Funder Id: 10.13039/501100002261).

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Received: 2017-08-31

Accepted: 2018-05-09

Published Online: 2018-07-13

Published in Print: 2018-08-28

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https://doi.org/10.1515/hc-2017-0192

Keywords for this article

3H-furan-2-one; azo compounds; cyclocondensation; heterocyclic; intramolecular; pyrazolo[5,1-c][1,2,4]triazine

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