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

1a Wei X. Taylor RJK. Tetrahedron Lett.  1998,  39:  3815 

1b Blackburn L. Wei X. Taylor RJK. Chem. Commun.  1999,  1337 

1c Wei X. Taylor RJK. J. Org. Chem.  2000,  65:  617 

2 Blackburn L. Pei X. Taylor RJK. Synlett  2002,  215 

3 Blackburn L. Taylor RJK. Org. Lett.  2001,  3:  1637 

4

For other tandem oxidation processes see the following two papers.

5a Gordon MS. Sojka SA. Krause JG. J. Org. Chem.  1984,  49:  97 

5b Tanimoto S. Yamadera T. Sugimoto T. Okano M. Bull. Chem. Soc. Jpn.  1979,  52:  4897 

5c Mauleon D. Granados R. Minguilon C. J. Org. Chem.  1983,  48:  3105 

6 Carey FA. Hayes LJ. J. Org. Chem.  1973,  38:  3107 

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]

9 Runcie KA. Taylor RJK. Chem. Commun.  2002,  974 

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.

11a Dubery IA. Holzhapfel CW. Kruger GJ. Schabort JC. Van Dyk M. Phytochemistry  1988,  27:  2769 

11b Dubery IA. Louw AE. van Heerden FR. Phytochemistry  1999,  50:  983 

12 Ito C. Tanahashi S. Tani Y. Ju-ichi M. Omura M. Furukawa H. Chem. Pharm. Bull.  1990,  38:  2586 

13 Zhang K. Corrie JET. Munasinghe VRN. Wan P. J. Am. Chem. Soc.  1999,  121:  5625 ; and references therein

14

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

15 Hegarty AF. Tuohey PJ. J. Chem. Soc., Perkin Trans. 2  1980,  1313