Microwave-Promoted Synthesis of 4-Arylpyrimidines by Pd-Catalysed Suzuki–Miyaura Coupling of 4-Pyrimidyl Tosylates in Water

Abstract

The Suzuki–Miyaura coupling reaction of 4-pyrimidyl tosylates was investigated with aryl, heteroaryl and alkyl boronic acids. The reaction provided 4-substituted pyrimidines in good-to-excellent yields after one-hour microwave irradiation in water at 100 °C. The method constitutes a fast option for the synthesis of these heterocyclic systems.

Key words

Suzuki–Miyaura coupling - pyrimidines - tosylates - microwave-accelerated synthesis - cross-coupling

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• 22 4-(4-Acetylphenyl)-6-methyl-2-phenylpyrimidine (3b)A 10-mL microwave vial was charged with 4-pyrimidyl tosylate 1a (0.588 mmol), the aryl boronic acid 2 (0.705 mmol), tetrakis(triphenylphosphine)palladium (0.029 mmol), powdered potassium carbonate (0.588 mmol) and water (5 mL). The resulting reaction mixture was irradiated for 1 h at 100 °C. The reaction mixture was then extracted three times with dichloromethane (ca. 15 mL each). The combined organic phases were dried with anhydrous sodium sulfate and filtered. The solvent was removed on a rotary evaporator and the crude product was purified by column chromatography (silica gel; n-hexane/EtOAc, 10:1) to obtain a yellow solid. Yield: 122 mg (87%); mp 148–150 °C; R_f = 0.72 (n-hexane/EtOAc, 5:1). IR (ATR): 3070, 2920, 1683, 1589, 1572 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 8.61–8.52 (m, 2 H, Ph), 8.25 (d, J = 8.4 Hz, 2 H, ArH), 8.06 (d, J = 8.4 Hz, 2 H, ArH), 7.60–7.47 (m, 3 H, Ph), 7.45 (s, 1 H, H-5), 2.64 (s, 3 H, COCH₃), 2.63 (s, 3 H, CH₃). ¹³C NMR (CDCl₃, 101 MHz): δ = 198.1, 168.6, 164.8, 162.7, 141.8, 138.8, 138.2, 131.1, 129.2, 128.9, 128.8, 127.8, 114.8, 27.2, 25.1. HRMS (ESI-TOF): m/z [M + H⁺] calcd for C₁₉H₁₇N₂O: 289.1341; found: 289.1342.