Practical Povidone Iodine Catalyzed Synthesis of 2,5-Disubstituted Oxazoles from Acetophenones and α-Amino Acids

Abstract

Nonharmful povidone iodine (PVP-I) was applied in the cyclization of acetophenones and α-amino acids to give 2,5-disubstituted oxazoles. Acetophenones with different substituents and natural α-amino acids were applied to our developed method, and more than 38 2,5-disubstituted oxazole compounds were obtained in moderate to good yields. Several naturally active 5-(3-indolyl)oxazole alkaloids such as pimprinine, labradorin, and pimprinol were successfully acquired in moderate yields using this strategy.

Key words

povidone iodine - acetophenones - α-amino acids - oxazoles - 5-(3-indolyl)oxazole alkaloids

Publication History

Received: 24 July 2024

Accepted after revision: 03 December 2024

Article published online:
10 January 2025

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• 25 Typical Procedure for the Preparation of 2-(sec-Butyl)-5-(p-tolyl)oxazole (3a) To a 25.0 mL round-bottomed flask were added 1a (2.5 mmol), 2a (2.5 mmol), PVP-I (10.0 mol%), CuCl₂·2H₂O (5.0 mmol), and DMSO (8.0 mL). The mixture was stirred at 80 °C for 16 h. After starting material was consumed completely (monitored by TLC), the mixture was suspended in water (20.0 mL) and extracted with EtOAc (3 × 10.0 mL). The organic layer was washed with saturated Na₂S₂O₃ solution (20.0 mL) and brine (20.0 mL) and then dried over Na₂SO₄. After filtration and concentration under reduced pressure, the residues were purified by flash column chromatography, eluting with n-heptane–EtOAc to afford pure 3a as a yellow oil (397 mg, 74%). ¹H NMR (400 MHz, CDCl₃): δ = 7.50 (d, J = 8.0 Hz, 2 H), 7.24 (s, 1 H), 7.20 (d, J = 8.0 Hz, 2 H), 2.97–2.95 (m, 1 H), 2.37 (s, 3 H), 1.90–1.85 (m, 1 H), 1.74–1.67 (m, 1 H), 1.38 (d, J = 6.0 Hz, 3 H), 0.95 (t, J = 7.2 Hz, 3 H). ¹³C NMR (151 MHz, CDCl₃): δ = 138.0, 129.5, 125.7, 124.0, 121.0, 35.4, 28.2, 21.3, 17.9, 11.7. EIMS (EI, 70 eV): m/z calcd for [C₁₄H₁₇NO]⁺: 215.1310; found: 215.1. R_f = 0.5 (n-heptane/EtOAc = 5:1)