Iodoarene-Mediated One-Pot Preparation of 2,4,5-Trisubstituted Oxazoles from Ketones

Abstract

2-Methyl-5-aryloxazole and 2-ethyl-5-aryloxazole derivatives were smoothly and efficiently obtained in one-pot manner from alkyl aryl ketones with iodoarene, m-chloroperbenzoic acid, and trifluoromethanesulfonic acid in acetonitrile and propionitrile, respectively. In these reactions, iodoarene works as a catalyst.

2,4,5-trisubstituted oxazoles - one-pot reaction - MCPBA - iodoarene

References and Notes

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<A NAME="RU10307ST-11">11</A> Typical Experimental Procedure: To a mixture of iodobenzene (purity 98%, 1.1 mmol, 228 mg) and MCPBA (purity 65%, 292 mg) in MeCN (8 mL) was added TfOH (2.0 mmol, 0.17 mL). The obtained mixture was stirred for 0.5 h at r.t. under an argon atmosphere. Then, a solution of acetophenone (purity 98.5%, 1.0 mmol, 122 mg) in MeCN (2 mL) was added, and the mixture was stirred for 2 h under refluxing conditions. After the reaction, the reaction mixture was poured into sat. aq NaHCO₃ solution and extracted with CHCl₃ (3 × 30 mL). The organic layer was dried over Na₂SO₄. After filtration and removal of the solvent under reduced pressure, the residue was purified by preparative TLC on silica gel (eluent: hexane-EtOAc, 5:1) to give 2-methyl-5-phenyloxazole in 56% yield. 2-Methyl-5-phenyloxazole: mp 57-58.5 °C (lit.¹² mp 57-58 °C). IR (KBr): 1580, 1560, 1480 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 2.53 (s, 3 H), 7.20 (s, 1 H), 7.30 (tt, J = 1.5, 7.8 Hz, 1 H), 7.40 (t, J = 7.8 Hz, 2 H), 7.60 (dd, J = 1.5, 7.8 Hz, 2 H). MS (FAB): m/z = 160 [M + H].Analytical data for selected oxazoles are as follows: 2-Methyl-5-(4′-chlorophenyl)oxazole: mp 71-72 °C (lit.¹³ mp 74-75.5 °C). IR (KBr): 3060, 1580, 1560, 1480, 1090, 820 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 2.53 (s, 3 H, s), 7.20 (s, 1 H), 7.38 (d, J = 8.9 Hz, 2 H), 7.54 (d, J = 8.9 Hz, 2 H). 2-Methyl-5-(4′-nitrophenyl)oxazole: mp 161-162 °C (lit.¹⁴ mp 167-168 °C). IR (KBr): 3020, 1610, 1560, 1500, 1350, 1330, 1130, 1110, 1060, 940, 850, 760 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 2.58 (s, 3 H), 7.42 (s, 1 H), 7.76 (d, J = 9.0 Hz, 2 H), 8.28 (d, J = 9.0 Hz, 2 H). MS (FAB): m/z = 205 [M + H]. 2-Methyl-5-(4′-methylphenyl)oxazole: mp 54-55 °C (lit.¹⁴ mp 56-57 °C). IR (KBr): 1580, 1560, 1500, 1460, 1380 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 2.37 (s, 3 H), 2.52 (s, 3 H), 7.15 (s, 1 H), 7.21 (d, J = 8.1 Hz, 2 H), 7.49 (d, J = 8.1 Hz, 2 H). 2-Ethyl-5-phenyloxazole: oil. IR (neat): 3060, 2980, 2940, 1580, 1560, 1490, 1450, 760, 690 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.40 (t, J = 7.6 Hz, 3 H), 2.86 (q, J = 7.6 Hz, 2 H), 7.22 (s, 1 H), 7.30 (tt, J = 1.4, 7.6 Hz, 1 H), 7.40 (dd, J = 7.6, 8.0 Hz, 2 H), 7.61 (dd, J = 1.4, 8.0 Hz, 2 H). HRMS: m/z [M + H] calcd for C₁₁H₁₂NO: 174.0919; found: 174.0922. 2-Ethyl-5-(4′-nitrophenyl)oxazole: mp 81-82 °C (lit.¹² mp 85-86 °C). IR (KBr): 3120, 2990, 1620, 1560, 1500, 1330, 750 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.42 (t, J = 7.6 Hz, 3 H), 2.90 (q, J = 7.6 Hz, 2 H), 7.44 (s, 1 H), 7.76 (d, J = 9.0 Hz, 2 H), 8.28 (d, J = 9.0 Hz, 2 H)

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