Microwave-Assisted Catalyst-Free Synthesis of Substituted 1,2,4-Triazoles

Abstract

A simple, efficient, and mild method has been developed for the synthesis of substituted 1,2,4-triazoles from hydrazines and formamide under microwave irradiation. The reaction proceeds smoothly in the absence of a catalyst and shows excellent functional-group tolerance.

Key words

microwave - microwave-assisted organic synthesis - 1,2,4-triazoles - aryl hydrazine - formamide

• References and Notes

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• 20 Experimental Procedure for the Synthesis of 3a To a dried microwave tube was added phenylhydrazine (108 mg, 1 mmol) and formamide (0.82 mL, 20 mmol). The tube was sealed with a plastic microwave septum and then placed into the microwave cavity and irradiated at 160 °C, 250 psi, and 230 W for 10 min. After completion of reaction (TLC), the mixture was cooled to r.t.; distilled H₂O (10 mL) was added, and the mixture extracted with EtOAc (3 × 10 mL). The combined organic extracts were dried over Na₂SO₄, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography using a mixture of n-hexane and EtOAc as eluent. Spectroscopic Data for Selected Triazoles 1-o-Tolyl-1H-1,2,4-triazole (3c) Pale yellow liquid. ¹H NMR (300 MHz, CDCl₃): δ = 8.20 (s, 1 H), 8.05 (s, 1 H), 7.36–7.19 (m, 4 H), 2.16 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 152.17, 143.80, 136.21, 133.90, 131.55, 129.66, 126.87, 126.06, 17.87. 1-(3-Chlorophenyl)-1H-1,2,4-triazole (3i) White solid; mp 94–96 °C. ¹H NMR (300 MHz, CDCl₃): δ = 8.57 (s, 1 H), 8.11 (s, 1 H), 7.74 (s, 1 H), 7.59 (d, J = 7.8 Hz, 1 H), 7.45 (t, J = 7.9 Hz, 1 H), 7.38 (d, J = 8.0 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 152.83, 140.91, 137.87, 135.65, 130.84, 128.26, 120.35, 117.85. 1-(3-Chloro-4-methylphenyl)-1H-1,2,4-triazole (3m) Off-white solid; mp 128–129 °C. ¹H NMR (300 MHz, CDCl₃): δ = 8.53 (s, 1 H), 8.09 (s, 1 H), 7.71 (d, J = 2.2 Hz, 1 H), 7.47 (dd, J = 8.2, 2.2 Hz, 1 H), 7.35 (d, J = 8.3 Hz, 1 H), 2.42 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 152.65, 140.79, 136.24, 135.69, 135.41, 131.78, 120.70, 117.95, 19.70. 1-tert-Butyl-1H-1,2,4-triazole (3p) Brownish liquid. ¹H NMR (300 MHz, CDCl₃): δ = 8.16 (s, 1 H), 7.94 (s, 1 H), 1.63 (s, 9 H). ¹³C NMR (75 MHz, CDCl₃): δ = 151.36, 139.77, 58.31, 29.41. 1-Cyclohexyl-1H-1,2,4-triazole (3q) White solid; mp 66–68 °C. ¹H NMR (300 MHz, CDCl₃): δ = 8.09 (s, 1 H), 7.93 (s, 1 H), 4.24–4.11 (m, 1 H), 2.22–2.15 (m, 2 H), 1.97–1.86 (m, 2 H), 1.83–1.68 (m, 3 H), 1.52–1.19 (m, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 151.34, 140.73, 59.37, 33.02, 25.12, 25.03.