Tandem Oxidation Processes: The Direct Conversion of Activated Alcohols into Esters and Amides

Abstract

The direct conversion of primary alcohols into methyl esters and amides using manganese dioxide and sodium cyanide with methanol or the appropriate amine is reported. These transformations, which proceed via an in situ four step, double oxidation sequence, have been applied to a range of benzylic, heterocyclic, allylic and propargylic alcohols.

oxidation - cyanide - cyanohydrin - acyl cyanide - 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:  616 

1d Runcie KA. Taylor RJK. Chem. Commun.  2002,  974 

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

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

4 Kanno H. Taylor RJK. Synlett  2002,  1287 

5 McAllister GD. Wilfred CD. Taylor RJK. Synlett  2002,  1291 

6 Corey EJ. Gilman NW. Ganem BE. J. Am. Chem. Soc.  1968,  90:  5616 

7 Gilman NW. J. Chem. Soc., Chem. Commun.  1971,  733 

8a

To a mixture of cinnamyl alcohol (134 mg, 1 mmol), sodium cyanide (49 mg, 1 mmol) and activated manganese dioxide (Aldrich 21764-6, 1.31 g, 15 mmol) stirring in tetrahydrofuran (10 mL), was added methanol (0.2 mL, 5 mmol). The reaction was heated to reflux and left to stir for 5 hours. The resulting mixture was then filtered through Celite^® and the solvent removed under reduced pressure. Extraction with dichloromethane (50 mL), was followed by washing with water (2 × 10 mL) and then saturated sodium chloride solution (10 mL), before drying over magnesium sulfate. Filtration and removal of solvent in vacuo gave methyl trans-cinnamate (113 mg, 70%), as light yellow crystals, which was pure according to ¹H NMR spectroscopy, mp 35 °C; lit. [14a] mp 35-36 °C.

8b

Ethyl acetate, methyl acetate, acetonitrile and dimethyl formamide were also investigated as co-solvents without leading to improved yields.

9

Alternatives to NaCN have also been investigated (e.g. KCN, LiCN, NaCl₂O, NaI, NaSCN, NaSCOMe, KOCN (using 2 equiv in each case). Only KCN (64%), LiCN (56%) and KOCN (6%) afforded methyl cinnamate.

10

Most of the esters and amides are known compounds and were identified by comparison of their ¹H NMR spectra with published data. Novel compounds were fully characterised.

11

A mixture of benzyl alcohol (108 mg, 1 mmol), iso-butylamine (0.5 ml, 5 mmol), sodium cyanide (49 mg, 1 mmol) and activated manganese dioxide (1.31 g, 15 mmol) was stirred in THF (15 mL) at r.t., After 30 min, a second batch of activated manganese dioxide (1.31 g, 15 mmol) was added and the reaction stirred for a further 23.5 h. The resulting mixture was then filtered through Celite^® with additional dichloromethane being used to wash the Celite^®. The combined organics were washed with water (2 × 20 mL) and then dried over magnesium sulfate. Filtration, removal of solvent in vacuo and chromatography on silica (petroleum ether-ether, 2:3) gave N-iso-butylbenzamide (153 mg, 86%), as a white solid, which was pure according to
¹H NMR spectroscopy; mp 55.8-56.1 °C (lit. [14b] mp
54-56 °C).

12

For an alternative manganese dioxide route to a limited range of carboxamides, which does not use sodium cyanide, see ref. [5]

13

Preliminary studies indicate that improved yields can be obtained with allylic alcohols if low temperatures (0 °C) are employed; the use of hexane as solvent can also improve yields in some cases. Further studies are being carried out which will be included in a full paper.

14a Kendall J. Booge JE. J. Am. Chem. Soc.  1916,  38:  1712 

14b Gajda T. Zwierzak A. Synthesis  1981,  1005