Synthesis of 1,3,4-Oxadiazoles from 1,2-Diacylhydrazines Using SO₂F₂ as a Simple and Practical Cyclization Reagent

Abstract

The synthesis of 1,3,4-oxadiazoles from 1,2-diacylhydrazines has been achieved using SO₂F₂ as a straightforward and effective reagent for dehydrative cyclisation, both in the absence of metal catalysts and under milder conditions. The reaction exhibited good functional group tolerance and yielded high levels of product.

Key words

SO₂F₂ - 1,3,4-oxadiazoles - cyclization - 1,2-diacylhydrazines

Publication History

Received: 14 October 2024

Accepted after revision: 26 November 2024

Accepted Manuscript online:
26 November 2024

Article published online:
03 February 2025

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• 15 2-[(1,1′-Biphenyl)-4-yl]-5-methyl-1,3,4-oxadiazol (2k) – Typical Procedure A mixture of N′-acetyl-(1,1′-biphenyl)-4-carbohydrazide (0.0282 g 0.1 mmol) and K₃PO₄ (0.0849 g 0.4 mmol) was added to a 100 mL sealed tube, followed by the addition of 1.5 ml of toluene solvent. Gas displacement of the sealed test tube was carried out by means of an SO₂F₂ balloon. The sealed tubes are then heated and stirred on a heating module at 90 °C for 4 h. At the end of the reaction, the reaction was washed with water (5 mL) and extracted with CH₂Cl₂ (3 × 5 mL), The organic phases were combined, dried (Na₂SO₄), and concentrated under vacuum. The residue was purified by column chromatography to give a light yellow solid; yield 0.0127 g (54%). ¹H NMR (400 MHz, CDCl₃): δ = 8.10 (d, J = 8.3 Hz, 2 H), 7.72 (d, J = 8.3 Hz, 2 H), 7.63 (d, J = 7.4 Hz, 2 H), 7.47 (t, J = 7.5 Hz, 2 H), 7.40 (t, J = 7.3 Hz, 1 H), 2.64 (s, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 164.8, 163.7, 144.3, 139.8, 129.0, 128.2, 127.7, 127.2, 127.1, 122.7, 11.2. HRMS-ESI: m/z calcd for C₁₅H₁₃N₂O [M + H]⁺: 237.1028; found: 237.1033.
• 16 2-Methyl-5-(naphthalen-2-yl)-1,3,4-oxadiazole (2l) – Typical Procedure A mixture of N′-acetyl-2-naphthohydrazide (0.0256 g 0.1 mmol) and K₃PO₄ (0.0849 g 0.4 mmol) was added to a 100 mL sealed tube, followed by the addition of 1.5 ml of toluene solvent. Gas displacement of the sealed test tube was carried out by means of an SO₂F₂ balloon. The sealed tubes are then heated and stirred on a heating module at 90 °C for 4 h. At the end of the reaction, the reaction was washed with water (5 mL) and extracted with CH₂Cl₂ (3 × 5 mL), The organic phases were combined, dried (Na₂SO₄), and concentrated under vacuum. The residue was purified by column chromatography to give a light yellow solid; yield 0.0109 g (52%). ¹H NMR (400 MHz, CDCl₃): δ = 8.50 (s, 1 H), 8.10 (dd, J = 8.6, 1.6 Hz, 1 H), 7.93 (d, J = 9.0 Hz, 2 H), 7.90–7.85 (m, 1 H), 7.56 (t, J = 4.7 Hz, 2 H), 2.65 (s, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 165.1, 163.8, 134.6, 132.8, 129.0, 128.8, 128.0, 127.9, 127.1, 127.1, 123.1, 121.2, 11.2. HRMS-ESI: m/z calcd for C₁₃H₁₁N₂O [M + H]⁺: 211.0871; found: 211.0866.