Regiospecific Synthesis of N2-Aryl 1,2,3-Triazoles from 2,5-Disubstituted Tetrazoles via Photochemically Generated Nitrile Imine Intermediates

Abstract

The synthesis of N2-aryl 1,2,3-triazoles from 2,5-disubstituted tetrazoles was achieved under photochemical conditions. This simple and mild one-step reaction provides regiospecific access to 2,4,5-substituted 1,2,3-triazoles via a nitrile imine intermediate. Syntheses of alkyl and heterocylic derivatives were also investigated.

Key words

photochemistry - regioselectivity - tetrazole - triazole - indazole

• References and Notes

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• 28 Representative Example for the Preparation of 2,5-Diaryl Tetrazoles: 5-Phenyl-2-(p-tolyl)-2H-tetrazole (5f) A solution of p-tolyl boronic acid (1.86 g, 13.7 mmol), 5-phenyl tetrazole (1.00 g, 6.84 mmol), and Cu₂O (5 mol%, 0.049 g, 0.342 mmol) in DMSO (30 mL) was stirred under O₂ (1 atm) at 110 °C for 6 h. The reaction mixture was allowed to cool, diluted with EtOAc (200 mL) and washed successively with 1 M HCl aq solution (30 mL) and brine (30 mL) three times. The organic phase was separated, dried, and concentrated in vacuo. Purification by flash column chromatography (Si, 50 g, 0–10% EtOAc–cyclohexane, 60 min) gave 5-phenyl-2-(p-tolyl)-2H-tetrazole 5f (1.51 g, 93%) as a white solid; mp 103–104 °C. IR: 1507, 1448, 1212, 1012 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 8.26 (dd, J = 2.0, 8.1 Hz, 2 H), 8.08 (d, J = 8.6 Hz, 2 H), 7.57–7.47 (m, 3 H), 7.38 (d, J = 8.6 Hz, 2 H), 2.46 (s, 3 H) ppm. ¹³C NMR (101 MHz, CDCl₃): δ = 165.1, 139.9, 134.8, 130.5, 130.2, 128.9, 127.3, 127.0, 120.0, 119.8, 77.3, 77.2, 77.0, 76.7, 21.2 ppm. HRMS (ESI⁺): m/z calcd for C₁₄H₁₃N₄: 237.1135; found: 237.1128. Representative Example for the Preparation of 2,4,5-Trisubstituted 1,2,3-Triazoles: 4,5-Diphenyl-2-(p-tolyl)-2H-1,2,3-triazole (9f) A solution of 5-phenyl-2-(p-tolyl)-2H-tetrazole 5f (200 mg, 0.85 mmol) in 2-PrOH–2-MeTHF (1:1, 10 mL) was stirred under irradiation with a UVB lamp (270–330 nm) for 19 h. The reaction mixture was concentrated in vacuo and the residue purified by reverse-phase chromatography (Si C₁₈, 50–95% MeCN–H₂O, HCO₂H modifier, 30 min) to give 4,5-diphenyl-2-(p-tolyl)-2H-1,2,3-triazole 9f (62 mg, 47%) as a brown gum. IR: 1510, 1441, 1268 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 8.10 (d, J = 8.6 Hz, 2 H), 7.72–7.65 (m, 4 H), 7.43 (dd, J = 1.9, 4.9 Hz, 6 H), 7.33 (d, J = 8.6 Hz, 2 H), 2.45 (s, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 145.7, 137.6, 137.3, 130.9, 129.8, 128.6, 128.6, 128.5, 127.1, 118.7, 21.1. HRMS (ESI⁺): m/z calcd for C₂₁H₁₈N₃: 312.1495; found: 312.1496.