Preparation of Symmetric and Nonsymmetric Imines from Primary Benzyl Amines by Means of an Oxidative Functionalization Reaction Using an Oxoammonium Salt Bearing the Nitrate Anion

Abstract

A methodology for the preparation of symmetric and nonsymmetric imines from primary benzyl amines is reported. The approach employs 4-acetamido-2,2,6,6-tetramethylpiperidin-1-oxoammonium nitrate (4-acetamido TEMPO), a recyclable oxoammonium salt bearing the nitrate anion, as the primary oxidant. It proves effective for a range of amine substrates bearing electron-withdrawing and -donating groups at ortho, meta, or para positions, along with disubstituted amines with the desired products being formed in good to excellent yield (75–97%). Nonsymmetric imine formation is achieved using aniline as a coupling partner with benzyl amines.

Key words

oxidation - oxoammonium salt - amines - imines - water - recyclable

Publication History

Received: 21 December 2024

Accepted after revision: 16 January 2025

Article published online:
07 March 2025

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• 28 General Procedure In a 10 mL glass microwave vial equipped with a stir bar was added the requisite amine (1 mmol, 1 equiv), 4-acetamido-2,2,6,6-tetramethyl-oxo-piperidinium nitrate (3, 0.7 equiv, 0.1925 g), and deionized water (0.5 mL). The vessel was sealed with a cap and the reaction mixture heated at 90 °C for 5 h. After completion of the heating step, the reaction mixture was cooled to room temperature and the contents of the vial extracted with hexanes. The hexanes washings were dried using anhydrous sodium sulfate and then the hexanes removed under vacuum to give the imine product.
• 29 General Procedure Step 1 To a 10 mL glass microwave vial equipped with a stir bar was added the requisite amine (0.5 mmol, 1 equiv), 4-acetamido-2,2,6,6-tetramethyl-oxo-piperidinium nitrate (3, 1.2 equiv, 0.165 g), and deionized water (0.5 mL). The vessel was sealed with a cap and the reaction mixture heated at 70 °C for 3 h. After completion of the heating step, the reaction mixture was cooled to room temperature. Step 2 To the vial from Step 1 was added aniline (0.5 mmol, 1 equiv, 0.0456 mL) and concentrated nitric acid (0.3 mmol, 0.6 equiv, 0.0191 mL). The vessel was sealed with a cap and the reaction mixture heated at 70 °C for another 2 h. After completion of the heating step, the reaction mixture was cooled to room temperature and the contents of the vial extracted with hexanes. The hexanes washings were dried using anhydrous sodium sulfate and then the hexanes removed under vacuum to give the imine product.
• 30 We were able to recover 60% of the hydroxylamine from the crude reaction mixture by adding 2 mL of an 8:2 mixture of hexane and ethyl acetate to the crude reaction mixture. White crystals of hydroxylamine precipitate and can be isolated by means of vacuum filtration.