Tandem Oxidation Processes: The Direct Conversion of Activated Alcohols into Oximes; Synthesis of Citaldoxime

Abstract

The direct conversion of primary alcohols into oximes is reported using manganese dioxide and alkoxylamines/hydroxyl­amine as their hydrochloride salts or supported on Amberlyst 15. This transformation has been applied to a range of benzylic, allylic and propargylic alcohols and utilised to prepare the natural product citaldoxime.

Key words

oxidation - O-alkyl oximes - oximes - citaldoxime - one-pot

References

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4

For other tandem oxidation processes see the following two papers.

7

Known products gave consistent spectroscopic data (and mps if solids); novel products were fully characterised.

8

Representative Procedure: Activated manganese dioxide (Aldrich, 21764-6; 0.87 g, 10 mmol) was added to a stirred solution of 4-nitrobenzyl alcohol (0.153 g, 1 mmol), methoxylamine hydrochloride (0.251 g, 3 mmol) and 4 Å molecular sieves (ca. 0.2 g) in dichloromethane (15 mL) and the mixture was heated to reflux for 22 h. After cooling, the reaction mixture was filtered through Celite^®, washing well with dichloromethane. The combined organic fractions were concentrated in vacuo and the resulting product purified by column chromatography on silica. Elution with petroleum ether-ethyl acetate (4:1) gave 4-nitrobenzaldehyde O-methyl oxime (0.154 g, 85%; E:Z = 13.1) as a yellow solid, mp 97.6-98.0 °C (lit. [15] mp for E-isomer, 102-104 °C) which displayed spectroscopic data consistent with those published. [5]

10

Representative procedure for the preparation of Amberlyst-supported alkoxylamine: A solution of sodium methoxide in methanol (4.37 M, 0.75 mL, 3.3 mmol) was added to a stirred solution of methoxylamine hydrochloride (0.251 g, 3 mmol) in methanol (10 mL) and the mixture was stirred at r.t. for 0.5 h. Amberlyst 15 (1.06 g, 5 mmol) was added and the resulting mixture was stirred for 1 h. The resin was removed by filtration, washed with methanol (50 mL) and dichloromethane (3 × 20 mL), and then used in the manganese dioxide reaction without further purification.

14

The yield was only 9% in dichloromethane at r.t. and 30% in refluxing THF.