Oxidation of Primary Amines to Ketones

Abstract

A simple method for the oxidation of primary amines to the corresponding ketones that proceeds in the presence of both moisture and air is described. Treatment of an amine with benzoyl peroxide in the presence of caesium carbonate, followed by warming of the hydroxylamine product to 50-70 ˚C leads directly to the ketone. The method is shown to be effective for both benzylic and aliphatic substrates.

amine - oxidation - hydroxylamine - benzoyl peroxide - ketone

References and Notes

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<A NAME="RD20008ST-27">27</A>

Typical Procedure for Conversion of N -Alkyl- O -benzoyl Hydroxylamines to Ketones: N-α-Methyl benzyl-O-benzoyl hydroxylamine (100 mg, 0.41 mmol) was dissolved in DMF (0.59 mL) at ambient temperature. Caesium carbonate (135 mg, 0.41 mmol) was added and the resulting reaction mixture was heated at 50 ˚C overnight. The resulting reaction mixture was allowed to cool and purified directly by column chromatography, eluting with 20% EtOAc-PE, to give acetophenone (42 mg, 84%) as a clear colourless oil. IR (thin film): 1683, 1599, 1582, 1449, 1359, 1266, 1180, 1078, 1025, 955, 760, 690 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 7.85 (d, J = 7.2 Hz, 2 H), 7.45 (t, J = 7.3 Hz, 1 H), 7.40-7.30 (m, 2 H), 2.50 (s, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 198.1, 137.1, 133.1, 128.6, 128.3, 26.6. MS (EI): m/z = 120.06 [M]⁺.
Typical Procedure for the One-Pot Conversion of Primary Amines to Ketones: Benzoyl peroxide (326 mg, 1.01 mmol, 75%) was dissolved in DMF (2.53 mL) and cooled to 0 ˚C. Caesium carbonate (493 mg, 1.51 mmol) was added with stirring followed by cyclohexyl ethylamine (0.18 mL, 1.21 mmol). The resulting reaction mixture was stirred at 0 ˚C for 2 h before warming to r.t. TLC was used to confirm complete consumption of benzoyl peroxide before heating at 50 ˚C overnight. The resulting reaction mixture was purified directly by column chromatography, eluting with 20% EtOAc-PE, to give cyclohexyl methyl ketone
(75 mg, 59%) as a clear colourless oil. IR (thin film): 2931, 2854, 1706 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 2.3-2.1 (m, 1 H), 2.05 (s, 3 H), 1.80-1.85 (m, 2 H), 1.70-1.75 (m,
2 H), 1.55-1.65 (m, 1 H), 1.05-1.30 (m, 5 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 212.2, 51.4, 28.4, 27.8, 25.8, 25.6. MS (EI): m/z = 126.22 [M]⁺.