Microwave-Assisted Molybdenum-Catalyzed Reductive Cyclization of o-Nitrobenzylidene Amines to 2-Aryl-2H-indazoles

Abstract

The reductive cyclization of o-nitrobenzylidene amines under microwave conditions employing MoO₂Cl₂(dmf)₂ as catalyst and Ph₃P as reducing agent delivers 2-aryl-2H-indazoles with yields ranging from 61–92%.

Key words

catalysis - cyclization - indazoles - molybdenum - Schiff bases

• References and Notes

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• 14 General Procedure for the Synthesis of o-Nitrobenzylidene Amines 3 o-Nitrobenzaldehyde 1 (10 mmol) and aniline 2 (10 mmol) in i-PrOH (3 mL) were placed in a round-bottomed flask and heated under reflux with magnetic stirring for 10 min. The reaction mixture was cooled to r.t., and the crystalline o-nitrobenzylidene amine 3 was isolated by filtration. The crude product was purified by crystallization from i-PrOH–EtOH = 1:1.
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• 17 General Procedure for the MoO₂Cl₂(dmf)₂-Catalyzed Reductive Cyclization of o-Nitrobenzylidene Amines 3 to 2-Aryl-2H-indazoles 4 A mixture of 3 (1 mmol), Ph₃P (2.4 mmol), MoO₂Cl₂(dmf)₂ (0.05 mmol), and toluene (3 mL) was sealed in a 10 mL septum reaction vial and irradiated with microwaves (Discover^TM by CEM, 2450 MHz, 300 W, 150 °C, 20 bar) for 10 min. After filtration and removal of the solvent the reaction mixture was poured into H₂O (50 mL) and extracted with EtOAc (3 × 30 mL). The combined organic extracts were washed with brine (30 mL). After drying over anhyd MgSO₄ and concentration in vacuo the resulting residue was purified by flash chromatography on silica gel (cyclohexane–EtOAc = 20:1). Alternatively, the reaction mixture can also be purified by flash column chromatography without any workup procedure.
• 18 Selected Data for 2-(2,4,6-Trimethylphenyl)-2H-indazole (4d) R_f = 0.36 (cyclohexane–EtOAc = 3:1). IR (ATR): 1627, 1518, 1490, 1377, 1349, 1267, 1195, 1144, 1044, 964, 939, 851, 782, 755, 733, 671 cm^–1. UV (MeCN): λ_max (log ε) = 276 nm (4.08). ¹H NMR (300 MHz, CDCl₃): δ = 7.96 (d, ⁵ Ј = 1.1 Hz, 1 H, 3-H), 7.81 [dq, ⁴ Ј and ⁵ Ј ~ 1.0 Hz, ³ Ј (6-H, 7-H) = 8.7 Hz, 1 H, 7-H], 7.75 [dt, ⁴ Ј and ⁵ Ј ~ 1.0 Hz, ³ Ј (4-H, 5-H) = 8.4 Hz, 1 H, 4-H], 7.34 [ddd, ⁴ Ј (4-H, 6-H) = 1.2 Hz, ³ Ј (5-H, 6-H) = 6.7 Hz, ³ Ј (6-H, 7-H) = 8.8 Hz, 1 H, 6-H], 7.15 [ddd, ⁴ Ј (5-H, 7-H) = 0.9 Hz, ³ Ј (5-H, 6-H) = 6.6 Hz, ³ Ј (4-H, 5-H) = 8.5 Hz, 1 H, 5-H], 6.99 (br s, 2 H, 3′-H and 5′-H), 2.37 (br s, 3 H, 4′′-H), 1.95 (br s, 6 H, 2′′-H and 6′′-H). ¹³C NMR (75 MHz, CDCl₃): δ = 149.1 (C-7a), 139.2 (C-4′), 137.3 (C-1′), 135.1 (C-2′ and C-6′), 128.7 (C-3′ and C-5′), 126.0 (C-6), 124.6 (C-3), 121.9 (C-5), 121.8 (C-3a), 120.3 (C-4), 118.0 (C-7), 21.1 (C-4′′), 17.1 (C-2′′ and C-6′′). MS (EI, 70 eV): m/z (%) = 336 (100) [M⁺], 221 (21), 220 (14), 28 (23). HRMS (EI): m/z calcd for C₁₆H₁₆N₂ [M⁺]: 236.1314; found: 236.1334.