Iron(II)-Catalyzed Denitration Reaction: Synthesis of 3-Methyl-2-arylimidazo[1,2-a]pyridine Derivatives from Aminopyridines and 2-Methylnitroolefins

Abstract

A variety of ways to synthesize imidazo[1,2-a]pyridines have been reported and many approaches are devoted to the functionalization of imidazo[1,2-a]pyridines. However, the use of a denitration reaction in the synthesis of imidazo[1,2-a]pyridines has not been reported. We report here the iron-catalyzed synthesis of 3-methyl-2-arylimidazo [1,2-a] pyridine derivatives from aminopyridines and 2-methyl-nitroolefins. The procedure, using FeCl₂ as catalyst, is simple and inexpensive. Various functional groups are tolerated and provide the products in good yields.

Key words

iron catalysis - denitration - heterocycles - cyclization - imidazo[1,2-a]pyridines

• References and Notes

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• 23 Typical Procedure for the Preparation of 3-Methyl-2-arylimidazo[1,2-a]pyridine: A test tube was charged with 1a (0.34 mmol), 2a (0.41 mmol) and FeCl₂ (3.81 mg, 0.03 mmol). Then DMF (2 mL) was added to the reaction system. The reaction was stirred at 150 °C for 7 h. After cooling to r.t., the solvent was diluted with EtOAc (10 mL) and washed with brine (5 mL) and dried over anhyd Na₂SO₄. After the solvent was evaporated in vacuo, the residues were purified by column chromatography, eluting with PE–EtOAc to afford pure 3aa (57 mg, 80%) as a white solid; mp 140–142 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.78–7.84 (m, 3 H), 7.62 (d, J = 9.2 Hz, 1 H), 7.45 (t, J = 7.6 Hz, 2 H), 7.31–7.34 (m, 1 H), 7.11–7.15 (m, 1 H), 6.78 (t, J = 6.8 Hz, 1 H), 2.58 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 144.2, 142.2, 134.7, 128.3, 128.2, 127.2, 123.3, 122.7, 117.2, 115.7, 111.8, 9.45. IR (neat): 3066, 3030, 2918, 1501, 1354, 1246, 773, 753, 700 cm^–1. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₄H₁₃N₂: 209.1073; found: 209.1077.