MICHAELIS–BECKER REACTION
1849
which is entirely consistent with the exclusive existence of either ionic or molecular phos-
phite forms II and IV within NMR detection limits. Sodium diethylphosphite recorded in
THF shows a single peak at 150.7 ppm,12 suggesting that alkali metal salts of secondary
dialkylphosphites have similar structures in both conventional polar organic solvents and
ionic liquids, and as such the higher selectivity for the Michaelis–Becker reaction in ionic
liquids remains to be explained. In summary, ionic liquids have been explored as alternative
solvents for the classical Michaelis–Becker reaction with the unexpected outcome that the
sodium hydroxide–promoted reaction proceeds relatively cleanly without dealkylation of
the phosphite or phosphonate product. We are currently investigating the mechanism of
this reaction and exploring additional C–P bond forming reactions in ionic liquids.
EXPERIMENTAL
Typical Procedure for Synthesis of Phosphonates
A 25 mL flask was charged with 1-butyl-3-methylimidazolium tetrafluoroborate
[bmim]BF4 (ca. 5 mL), pulverized NaOH (0.0512 g, 1.28 mmol), and a magnetic stir
bar. The flask was stirred and heated in an oil bath until the sodium hydroxide dissolved
and then removed from the oil bath. Then, dibutylphosphite (0.25 mL, 1.3 mmol) was
added to via syringe. The resulting mixture was stirred for 15 min, and iodomethane (0.08
mL, 1 mmol) was added to the flask in a single portion and the mixture was stirred for
12 h. The ionic liquid layer was extracted with diethyl ether (ca. 3 mL) and the ether layer
was removed under oil-pump vacuum. The resulting residue was chromatographed (silica
gel, 90:10 hexane:EtOAc) to give methyl dibutylphosphonate (0.189 g, 0.908 mmol, 91%
yield).
REFERENCES
1
2
3
4
. A. Michaelis and T. Becker, Chem Ber., 30, 1003 (1897).
. A. K. Battacharya and G. Thyagarajan, Chem. Rev., 81, 415 (1981).
. H. Fakhraian and A. Mirzaei, Phosphorus, Sulfur, and Silicon, 181, 511 (2006).
. D. J. Adams, P. J. Dyson, and S. J. Tavener, Chemistry in Alternative Reaction Media (Wiley,
Chichester, UK, 2004).
5
. For examples of the use of NaOH in ionic liquids see: (a) M. J. Earle, P. B. McCormac, and
K. R. Seddon, Green Chem., 2, 261 (2000); (b) R. J. C. Brown, P. J. Dyson, D. J. Ellis, and T.
Welton, Chem Commun., 1862 (2001); (c) D. W. Morrison, D. C. Forbes, and J. H. Davis, Jr.,
Tetrahedron Lett., 42, 6053 (2001).
6
7
. T. Ramnial, D. D. Ino, and J. A. C. Clyburne, Chem. Comm., 325 (2005).
. Our yields of phosphonates obtained when synthesized using the classical Michaelis–Becker
reaction were in the range 14–63%. See ref. [8].
8
. E. Muller, Ed., Methoden der organischen Chemie (Houben-Weyl), vol. 7 (George Thieme Verlag,
Stuggart, Germany, 1964).
9. A. K. Gupta, R. Kumar, D. K. Dubey, and M. P. Kaushik, J. Chem. Res., 328 (2007) and references
therein.
1
1
1
0. M. Zanger, C. A. Vander Werf, and W. E. McEwen, J. Am. Chem. Soc., 81, 3806 (1959).
1. G. O. Doak and L. D. Freedman, Chem. Rev., 61, 31 (1961).
2. W. Boenigk and G. H a¨ gele, Chem Ber., 117, 2287 (1984).