Oxidation of Alcohols to Aldehydes and Ketones Using a Catalytic Pairing of a Nitroxide and Nitric Acid

Abstract

A methodology for the oxidation of alcohols to aldehydes and ketones is presented. The approach employs catalytic quantities of a nitroxide and nitric acid, with no additives or metal catalysts being required. It proves effective for a range of aromatic, heteroaromatic, and aliphatic alcohol substrates, the desired products being formed in good to excellent yield. In the case of primary alcohols, the oxidation can be stopped at the aldehyde without concomitant formation of the corresponding carboxylic acid.

Key words

oxidation - nitroxide - nitric acid - aldehydes - ketones - alcohols

Publication History

Received: 24 October 2023

Accepted after revision: 22 November 2023

Accepted Manuscript online:
27 November 2023

Article published online:
21 December 2023

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• 20 General Procedure To a 4-dram reaction vial equipped with a stir bar were added the starting material (2 mmol, 1 equiv), 4-acetamido-2,2,6,6-tetramethylpiperidin-1-oxyl (ACT, 85mg, 0.2 equiv), 2 mL of dichloromethane, and nitric acid (70%, 0.051 mL, 0.4 equiv). The vial was closed tightly. The contents were then heated in a sand bath at 55 °C. Upon completion, the product mixture was loaded onto a pad of silica gel. Diethyl ether or dichloromethane was passed through the silica gel, first eluting any unreacted alcohol and then the product. The nitroso intermediate and any carboxylic acid formed in the reaction remain adsorbed on the silica. The solvent was then removed from the filtrate of the product under vacuum, affording the aldehyde or ketone in pure form.
• 21 Representative Spectral Data Octanal (6a) Obtained as colorless oil in 3 h (0.233 g, 89%). ¹H NMR (400 MHz, CDCl₃): δ = 9.76 (t, J = 1.9 Hz, 1 H), 2.41 (td, J = 7.3, 1.9 Hz, 2 H), 1.63 (p, J = 7.3 Hz, 2 H), 1.30 (dd, J = 8.5, 5.4 Hz, 8 H), 0.92 0.84 (m, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 202.96, 77.33, 77.01, 76.69, 43.92, 31.62, 29.13, 29.01, 22.58, 22.10, 14.04. 4-(Trifluoromethyl)benzaldehyde (6d) Obtained as light-yellow oil in 1 h (0.306 g, 88%). ¹ H NMR (400 MHz, CDCl₃): δ = 10.11 (s, 1 H), 8.01 (d, J = 7.9 Hz, 2 H), 7.82 (d, J = 8.0 Hz, 2 H). ¹³C NMR (101 MHz, CDCl₃): δ = 191.04, 129.92, 126.15, 126.11. ¹⁹F NMR (376 MHz, CDCl₃): δ = –63.10, –161.64. Furfural (6j) Obtained as yellow liquid in 1 h (0.123 g, 64%). ¹H NMR (400 MHz, CDCl₃): δ = 9.66 (s, 1 H), 7.71–7.64 (m, 1 H), 7.25 (dd, J = 3.6, 0.8 Hz, 1 H), 6.60 (dd, J = 3.6, 1.7 Hz, 1 H). ¹³C NMR (101 MHz, CDCl₃): δ = 177.88, 153.03, 148.06, 120.91, 112.58. 4-Methoxyacetophenone (6o) Obtained as a yellow oil in 2 h (0.266 g, 88%). ¹H NMR (400 MHz, CDCl₃): δ = 7.98–7.89 (m, 2 H), 6.97–6.89 (m, 2 H), 3.87 (s, 3 H), 2.55 (s, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 196.77, 163.50, 130.59, 130.38, 113.69, 55.47, 26.34. 1-Phenyl-2-propyl-1-one (6t) Obtained as yellow solid in 1 h (0.212 g, 82%). ¹H NMR (400 MHz, CDCl₃): δ = 8.20–8.06 (m, 2 H), 7.68–7.59 (m, 1 H), 7.56–7.45 (m, 2 H), 3.44 (s, 1 H). ¹³C NMR (101 MHz, CDCl₃): δ = 177.41, 136.17, 134.53, 129.72, 128.70, 80.76, 80.29. 2-Adamantanone (6w) Obtained as white solid in 1 h (0.265 g, 90%). ¹H NMR (400 MHz, CDCl₃): δ = 2.54 (d, J = 4.7 Hz, 2 H), 2.14–1.96 (m, 12 H). ¹³C NMR (101 MHz, CDCl₃): δ = 46.98, 39.29, 36.32, 27.46.