A Green and Facile Synthesis of Biopertinent Pyrazole-Decorated Nitriles and Acrylates under Catalyst-Free Conditions

Abstract

A green and efficient methodology has been developed for the construction of 2-[(1,3-diaryl-4-pyrazolyl)methylene]malononitriles, potent antioxidant molecules, in good to excellent yields in five minutes from 1,3-diarylpyrazole-4-carbaldehydes and malononitrile using PEG-400 and water at ambient temperature under catalyst-free conditions. The PEG-400 could be reused without appreciable loss in the yield. The methodology has been extended to the synthesis of a diverse range of homo/heteroaryl-based nitriles and acrylates, reflecting its versatility.

Key words

pyrazoles - green chemistry - condensation

• References and Notes

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• 9 Typical Experimental Procedure An equimolar quantity of 3-(4-bromophenyl)-1-phenylpyrazolecarbaldehyde (1.0 mmol) and malononitrile (1.0 mmol) was stirred in polyethylene glycol (PEG-400)–H₂O (3:1) mixture at ambient temperature for 5 min when a solid was obtained. H₂O was then added, and the mixture was filtered and dried under reduced pressure to give 2-{[3-(4-bromophenyl)-1-phenylpyrazolyl]methylene}malononitrile (1a). Recrystallization from an EtOH–DMF mixture afforded analytically pure product as a pale yellow solid; mp 199–200 °C. IR (KBr): ν = 2362.8, 2223.9, 1570.1, 1518.0, 1436.9, 1402.2, 1338.6, 1240.2, 1076.3, 1008.8, 974.1, 954.8, 831.2, 812.0, 754.2, 729.1, 705.9, 682.8, 630.7, 609.5 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 9.01 (s, 1 H), 7.74–7.63 (m, 5 H), 7.50–7.41 (m, 5 H). ¹³C NMR (75 MHz, CDCl₃): δ = 156.2, 151.3, 138.6, 132.5, 131.5, 130.2, 129.4, 128.9, 126.5, 123.9, 120.0, 115.0, 114.7, 114.0, 78.3. GC–MS: m/z = 374 [M⁺]. Anal. Calcd for C₁₉H₁₁BrN₄: C, 60.82; H, 2.95; N, 14.93. Found: 60.85; H, 2.91; N, 14.91.
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• 13 Characterization Data of Representative Unsubstituted Nitrile 1f Pale yellow solid; mp 214–215 °C. IR (KBr): ν = 2357.0, 2223.9, 1581.6, 1521.8, 1502.6, 1469.8, 1448.5, 1344.4, 1238.3, 1184.3, 1018.4, 952.8, 821.7, 758.0, 715.6, 678.9, 611.4 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 9.06 (s, 1 H), 7.84–7.80 (m, 3 H), 7.58–7.52 (m, 7 H), 7.47–7.44 (m, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 156.3, 151.0, 138.5, 130.6, 129.6, 129.5, 129.3, 129.1, 128.9, 119.9, 114.9, 113.8, 78.5. GC–MS: m/z = 296 [M⁺]. Anal. Calcd for C₁₉H₁₂N₄: C, 77.01; H, 4.08; N, 18.91. Found: 77.05; H, 4.11; N, 18.88.
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• 16 Characterization Data of Representative Acrylate 3a Off-white solid; mp 106–107 °C. IR (KBr): ν = 2987.7, 2218.1, 1726.3, 1643.4, 1593.2, 1519.9, 1429.3, 1373.3, 1267.2, 1236.4, 1190.1, 1093.6, 1020.3, 947.1, 887.3, 817.8, 721.2, 673.2, 578.6, 526.6 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 9.14 (s, 1 H), 8.24 (s, 1 H), 7.82 (d, J = 8.0 Hz, 2 H), 7.55–7.47 (m, 7 H), 7.41 (t, J = 6.9 Hz, 1 H), 4.37–4.32 (m, 2 H), 1.37 (t, J = 7.2 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 162.6, 155.1, 145.7, 138.8, 135.7, 130.4, 129.7, 129.4, 129.3, 128.3, 120.0, 116.6, 114.9, 100.2, 62.5, 14.2. MS: m/z = 377 [M⁺]. Anal. Calcd for C₂₁H₁₆ClN₃O₂: C, 66.76; H, 4.27; N, 11.12. Found: C, 66.85; H, 4.33; N, 11.01.