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.

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

References

<A NAME="RD08702ST-1A">1a</A> Wei X. Taylor RJK. Tetrahedron Lett.  1998,  39:  3815 

<A NAME="RD08702ST-1B">1b</A> Blackburn L. Wei X. Taylor RJK. Chem. Commun.  1999,  1337 

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<A NAME="RD08702ST-2">2</A> Blackburn L. Pei X. Taylor RJK. Synlett  2002,  215 

<A NAME="RD08702ST-3">3</A> Blackburn L. Taylor RJK. Org. Lett.  2001,  3:  1637 

<A NAME="RD08702ST-4">4</A>

For other tandem oxidation processes see the following two papers.

<A NAME="RD08702ST-5A">5a</A> Gordon MS. Sojka SA. Krause JG. J. Org. Chem.  1984,  49:  97 

<A NAME="RD08702ST-5B">5b</A> Tanimoto S. Yamadera T. Sugimoto T. Okano M. Bull. Chem. Soc. Jpn.  1979,  52:  4897 

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

<A NAME="RD08702ST-8">8</A>

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]

<A NAME="RD08702ST-9">9</A> Runcie KA. Taylor RJK. Chem. Commun.  2002,  974 

<A NAME="RD08702ST-10">10</A>

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.

<A NAME="RD08702ST-11A">11a</A> Dubery IA. Holzhapfel CW. Kruger GJ. Schabort JC. Van Dyk M. Phytochemistry  1988,  27:  2769 

<A NAME="RD08702ST-11B">11b</A> Dubery IA. Louw AE. van Heerden FR. Phytochemistry  1999,  50:  983 

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<A NAME="RD08702ST-13">13</A> Zhang K. Corrie JET. Munasinghe VRN. Wan P. J. Am. Chem. Soc.  1999,  121:  5625 ; and references therein

<A NAME="RD08702ST-14">14</A>

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

<A NAME="RD08702ST-15">15</A> Hegarty AF. Tuohey PJ. J. Chem. Soc., Perkin Trans. 2  1980,  1313