A Metal-Free Oxidative Amination of Benzoxazoles with Primary Amines and Ammonia

Abstract

An efficient synthesis of 2-aminobenzoxazoles is described by a direct oxidative amination of unfunctionalized benzoxazoles with primary amines. The reaction could be performed in the absence of transition metals by using catalytic amounts of a quaternary ammonium iodide and tert-butylhydroperoxide as a cheap and easy-to-handle co-oxidant. In addition to primary amines, aqueous solutions of NH₃ were used to introduce a primary amine group into the heterocyclic core.

green chemistry - amination - homogeneous catalysis - iodine - oxidation

References and Notes

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<A NAME="RD23611ST-10">10</A>

The reaction between benzo[d]oxazole and N-butylamine was described in our previous oxidative amination procedure (see ref. 8). However, this was the only example of a primary amine in this article.

<A NAME="RD23611ST-11">11</A>

Typical Experimental Procedure A reaction vessel was charged with AcOH (0.061 g, 1.010 mmol, 3 equiv) and TBHP (70% solution in H₂O, 0.065 g, 0.504 mmol, 1.5 equiv) in MeCN (0.2 mL). After the addition of TBAI (0.006 g, 0.017 mmol, 5 mol%), 1-phenyl-ethylamine (2f, 0.029 g, 0.403 mmol, 1.2 equiv), and benz-oxazole (1a, 0.040 g, 0.336 mmol, 1 equiv) in MeCN (0.2 mL) were added. The reaction mixture was stirred until TLC showed full conversion of benzoxazole (1.5 h). The reaction was quenched by addition of an aq solution of Na₂S₂O₅ (2 mL) and a sat. solution of NaHCO₃ (5 mL). The mixture was extracted with CH₂Cl₂ (5 × 5 mL), combined organic phases were dried over Na₂SO₄, and the solvent was removed in vacuo. The residue was purified by column chromatography [silica gel; hexane-EtOAc = 10:1 (v/v)] to yield 3f (0.061 g, 81%) as a white amorphous solid. ^¹H NMR (400 MHz, CDCl₃): δ = 7.43-7.41 (m, 2 H), 7.34-7.31 (m, 2 H), 7.28-7.20 (m, 3 H), 7.12 (t, 1 H, J = 7.7 Hz), 6.99 (t, 1 H, J = 7.7 Hz), 6.88 (br s, 1 H), 5.11 (q, 1 H, J = 6.8 Hz), 1.66 (d, 3 H, J = 6.7 Hz). ^¹³C{^¹H} NMR (100 MHz, CDCl₃): δ = 161.6, 148.4, 143.4, 142.7, 128.7, 127.4, 125.9, 123.8, 120.6, 116.0, 108.8, 52.8, 23.1. IR (neat): 2970, 1658, 1648, 1580, 1458, 1366, 1217, 698 cm^-¹. HRMS (EI): m/z calcd for C₁₅H₁₅N₂O₂ [M + H]⁺: 239.1179; found: 239.1178. Anal. Calcd for C₁₅H₁₄N₂O₂: C, 75.61; H, 5.92; N, 11.76. Found: C, 75.96; H, 5.56; N, 11.88. Detailed spectroscopic data as well as ^¹H and ^¹³C NMR spectra of all compounds 3a-v are given in the Supporting Information.