Synthesis of Substituted 1-Benzyl-2H-1,2,3-Triazoles by a Click Reaction Using Calcium Carbide as an Acetylene Source

Abstract

An effective strategy for constructing substituted 1-benzyl-1H-1,2,3-triazoles was developed through click reactions of benzylic halides with sodium azide and calcium carbide as sources of nitrogen and acetylene, respectively. The advantages of this method are an easily handled inexpensive source of acetylene, a wide range of substrates, satisfactory yields, and simple workup procedures, which could promote the use of calcium carbide as a sustainable acetylene source in modern industrial chemistry.

Key words

sodium azide - calcium carbide - click chemistry - benzyl halides - triazoles

Publikationsverlauf

Eingereicht: 30. Juli 2024

Angenommen nach Revision: 12. September 2024

Accepted Manuscript online:
12. September 2024

Artikel online veröffentlicht:
08. Oktober 2024

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• 19 1-(2-Phenoxybenzyl)-1H-1,2,3-triazole (2t); Typical Procedure A mixture of 1-(chloromethyl)-2-phenoxybenzene (0.5 mmol, 0.109 g), 72–82% pure calcium carbide (2.4 mmol, 0.153 g), NaN₃ (0.6 mmol, 0.040 g, 1.2 equiv), CuI (0.05 mmol, 0.0095 g, 10 mol%), Et₃N (0.5 mmol, 0.5ml), H₂O (3 mmol, 54 μL, 6.0 equiv) in DMF (3 mL) was heated with stirring in an oil bath at 80 °C for 10 h until the reaction complete (TLC). The resulting mixture was filtered to remove the solids and the liquor was extracted with EtOAc (3 × 10 mL). The extracts were washed with sat. brine (3 × 10 mL), dried (Na₂SO₄), and concentrated under reduced pressure. The crude product was crystallized from PE–EtOAc to give a white solid; yield: 80.8 mg (65%); mp 82–85 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.67 (d, J = 1.0 Hz, 1 H), 7.57 (d, J = 1.0 Hz, 1 H), 7.41–7.26 (m, 4 H), 7.18–7.07 (m, 2 H), 7.00–6.92 (m, 2 H), 6.87 (dd, J = 8.2, 1.1 Hz, 1 H), 5.65 (s, 2 H). ¹³C NMR (101 MHz, CDCl₃): δ = 156.5, 154.9, 133.9, 130.6, 130.3, 130.0, 125.8, 123.9, 123.9, 123.7, 118.7, 118.4, 48.8. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₅H₁₃N₃NaO: 274.0951; found: 274.0953. 1-(2-Bromo-5-methoxybenzyl)-1H-1,2,3-triazole (2ad) White solid: 94.5 mg (71%); mp 74–76 °C (PE–EtOAc). ¹H NMR (400 MHz, CDCl₃): δ = 7.71 (d, J = 1.1 Hz, 1 H), 7.61 (d, J = 1.0 Hz, 1 H), 7.47 (d, J = 8.8 Hz, 1 H), 6.76 (dd, J = 8.8, 3.0 Hz, 1 H), 6.64 (d, J = 3.0 Hz, 1 H), 5.63 (s, 2 H), 3.71 (s, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 159.4, 135.1, 134.2, 133.8, 123.8, 116.2, 115.7, 113.5, 55.5, 53.7. HRMS (ESI): m/z [2M + Na]⁺ calcd for C₂₀H₂₀Br₂N₆NaO₂: 558.9887; found: 558.9886.