Ligand-Free Copper(I) Oxide Nanoparticle Catalyzed Three-Component ­Synthesis of 2H-Indazole Derivatives from 2-Halobenzaldehydes, Amines and Sodium Azide in Polyethylene Glycol as a Green Solvent

Abstract

An efficient synthesis of 2H-indazole derivatives based on the one-pot three-component reaction of 2-chloro- and 2-bromobenzaldehydes, primary amines and sodium azide is described. The reaction is catalyzed by copper(I) oxide nanoparticles (Cu₂O-NP) under ligand-free conditions in polyethylene glycol (PEG 300) as a green solvent.

Key words

Cu₂O nanoparticle - 2H-indazole derivatives - ligand-free - three-component - green solvent

• References and Notes

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• 20 General Procedure: To a mixture of 2-bromobenzaldehyde (1.0 mmol) or 2-chlorobenzaldehyde (1.0 mmol), amine (1.1 mmol) and NaN₃ (2.0 mmol) in polyethylene glycol (PEG 300; 3.0 mL) was added the Cu₂O-NP catalyst (5 mol%) and the mixture was stirred at 120 °C for 2-bromobenzaldehyde or at 170 °C for 2-chlorobenzaldehyde. The progress of the reaction was monitored by TLC using n-hexane–EtOAc (10:1). After completion of the reaction, the reaction mixture was cooled to r.t., the mixture was poured into EtOAc (30.0 mL) and washed with deionized H₂O (3 × 20.0 mL) and brine (3 × 20.0 mL). The organic layer was dried (CaCl₂), filtered and evaporated in vacuo to give the crude product, which was purified by silica gel column chromatography employing n-hexane–EtOAc (10:1) as eluent. Typical Characterization Data for Some Compounds:
  2-p-Tolyl-2H-indazole (4a): pale yellow solid; mp 98–100 °C. IR (KBr): 748, 786, 817, 1041, 1118, 1195, 1380, 1450, 1519, 1620, 2947, 3039, 3129 cm^–1. ¹H NMR (250 MHz, CDCl₃): δ = 2.43 (s, 3 H), 7.08–7.14 (m, 1 H), 7.30–7.35 (m, 3 H), 7.71 (d, J = 8.5 Hz, 1 H), 7.77–7.82 (m, 3 H), 8.37 (d, J = 0.7 Hz, 1 H). ¹³C NMR (62.9 MHz, CDCl₃): δ = 21.0, 117.8, 120.3, 120.4, 120.8, 122.3, 122.7, 126.7, 130.1, 137.9, 138.2, 149.6. MS: m/z (%) = 210 (9.0) [M⁺ + 2], 209 (89.6) [M⁺ + 1], 208 (100.0) [M⁺], 165 (51.4), 91 (61.1), 65 (68.1). Anal. Calcd for C₁₄H₁₂N₂ (208.262): C, 80.74; H, 5.81; N, 13.45. Found: C, 80.70; H, 5.87; N, 13.51. 4-(2H-Indazol-2-yl)-N,N-dimethylaniline (4f): orange solid; mp 185–187 °C. IR (KBr): 732, 779, 817, 941, 1049, 1141, 1195, 1226, 1350, 1434, 1519, 1596, 2923, 3055 cm^–1. ¹H NMR (250 MHz, CDCl₃): δ = 3.02 (s, 6 H), 6.80 (d, J = 9.0 Hz, 2 H), 7.07–7.13 (m, 1 H), 7.27–7.33 (m, 1 H), 7.68–7.75 (m, 3 H), 7.79 (d, J = 8.5 Hz, 1 H), 8.29 (s, 1 H). ¹³C NMR (62.9 MHz, CDCl₃): δ = 40.5, 111.7, 112.4, 117.6, 119.9, 120.2, 121.9, 122.1, 122.6, 124.0, 126.1, 130.4, 149.3, 150.1. MS: m/z (%) = 239 (13.7) [M⁺ + 2], 238 (73.4) [M⁺ + 1], 237 (100.0) [M⁺], 208 (47.5), 165 (32.0), 118 (21.3), 69 (38.2). Anal. Calcd for C₁₅H₁₅N₂ (237.304): C, 75.92; H, 6.37; N, 17.71. Found: C, 75.97; H, 6.48; N, 17.82. 2-(4-Chlorophenyl)-2H-indazole (4h): white solid; mp 139–141 °C. IR (KBr): 748, 817, 948, 1002, 1087, 1195, 1380, 1419, 1488, 15.21, 1627, 3062, 3132 cm^–1. ¹H NMR (250 MHz, CDCl₃): δ = 7.09–7.15 (m, 1 H), 7.30–7.36 (m, 1 H), 7.47–7.50 (m, 2 H), 7.69 (d, J = 8.5 Hz, 1 H), 7.78 (d, J = 8.7 Hz, 1 H), 7.83–7.86 (m, 2 H), 8.36 (s, 1 H). ¹³C NMR (62.9 MHz, CDCl₃): δ = 117.9, 120.2, 120.4, 121.9, 122.7, 122.9, 127.1, 129.6, 133.5, 138.9, 149.9. MS: m/z (%) = 230 (35.1) [M⁺ + 2], 229 (79.8) [M⁺ + 1], 228 (100.0) [M⁺], 193 (57.4), 166 (77.7), 139 (24.5), 111 (51.1), 75 (60.6). Anal. Calcd for C₁₃H₉ClN₂ (228.681): C, 68.28; H, 3.97; N, 12.25. Found: C, 68.22; H, 4.07; N, 12.32.