Simple and Efficient One-Pot Synthesis of Imidazo[1,2-a]pyridines Catalyzed by Magnetic Nano-Fe₃O₄–KHSO₄·SiO₂

Abstract

The present report highlights a magnetic nano-Fe₃O₄–KHSO₄·SiO₂ catalyzed synthesis of imidazo[1,2-a]pyridines. The synthetic strategy adopted is expedient, versatile, and offers good to excellent yields from readily available starting materials.

Key words

multicomponent reactions - transition metals - hetero­cycles - heterogeneous catalysis - iron

• References

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• 8 General Experimental Procedure: To an oven-dried 25 mL round-bottom flask containing a magnetic stir bar was added 2-aminopyridine (1 mmol, 94.1 mg), aldehyde (1 mmol), KHSO₄·SiO₂ (150 mg, 0.032 mmol with respect to KHSO₄), and anhyd toluene (2 mL). The mixture was stirred for 15 min and to it was then added alkyne (1.2 mmol) and nano-Fe₃O₄ [<50 nm particle size, ≥98% trace metals basis (Aldrich)] (0.1 mmol, 23.2 mg). The total reaction mixture was refluxed at 110 °C for the appropriate time. After completion of the reaction (monitored by TLC), EtOAc was added (10 mL), the magnetic Fe₃O₄ nanoparticles were collected on the magnetic stir bar, and the mixture was filtered through a porous plug. The filtrate was concentrated under reduced pressure and the crude product thus obtained, was purified by silica gel column chromatography (EtOAc–hexane, 1:9). The pure products were characterized based upon their physical and spectroscopic properties. Spectroscopic Data of the Representative Compounds: 3-Benzyl-2-(3-chlorophenyl)imidazo[1,2-a]pyridine (4c): White solid; mp = 141–142 °C. ¹H NMR (300 MHz, CDCl₃): δ = 7.77 (s, 1 H), 7.65–7.53 (m, 3 H), 7.27–7.22 (m, 4 H), 7.21–7.10 (m, 2 H), 7.07 (d, J = 6.6 Hz, 2 H), 6.68–6.64 (m, 1 H), 4.42 (s, 2 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 143.7, 142.2, 136.1, 135.9, 134.4, 132.0, 129.9, 129.6, 129.3, 128.1, 127.9, 127.7, 126.9, 126.3, 124.8, 123.3, 118.0, 117.7, 112.4, 29.9 ppm. 3-Benzyl-2-(4-tolyl)imidazo[1,2-a]pyridine (4i): Pale yellow solid; mp = 160–161 °C. ¹H NMR (300 MHz, CDCl₃): δ = 7.69 (t, J = 8.1 Hz, 4 H), 7.26 (br s, 5 H), 7.16–7.13 (m, 3 H), 6.70 (br s, 1 H), 4.49 (s, 2 H), 2.39 (s, 3 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 144.6, 144.0, 137.7, 136.6, 131.9, 129.0, 128.9, 128.2, 127.6, 126.7, 124.1, 123.1, 117.5, 117.3, 112.0, 30.1, 21.1 ppm.
• 9 For the preparation of KHSO₄·SiO₂, see: Goswami N, Das RN, Borthakur N. Ind. J. Chem., Sect. B: Org. Chem. Incl. Med. Chem. 2007; 46: 1893
• 10 Reusability of magnetic nano-Fe₃O₄: After completion of the reaction EtOAc was added and the Fe₃O₄-nanoparticles were recovered by the application of an external magnet. The recovered nanoparticles were thoroughly washed with Et₂O, dried at 130 °C for 1 h and then reused for a new catalytic cycle.