An Improved Bouveault-Blanc Ester Reduction
with Stabilized Alkali Metals
Brian S. Bodnar* and Paul F. Vogt
Process DeVelopment SerVices, SiGNa Chemistry, Inc.,
1 Deer Park DriVe, Suite C, Monmouth Junction,
New Jersey 08852
FIGURE 1. Improved Bouveault-Blanc procedure using Na-SG(I).
ReceiVed December 19, 2008
substrate.3 While the Bouveault-Blanc reduction can be suc-
cessfully employed in large-scale continuous or batch
processes,1d the reaction conditions may result in excessive
foaming and even fires.2a,3b
Recently, we have developed technology for encapsulating
alkali metals into nanostructured porous oxides, which reduces
the dangers associated with the handling of alkali metals while
retaining the reducing power of the metal.4 Sodium or
sodium-potassium alloys in silica gel (Na-SG, Na2K-SG, and
K2Na-SG) are free-flowing solids that have demonstrated
applications in desulfurization,4b Birch reduction,4b and
detosylation4c at room temperature. Herein, we present the use
of Stage I sodium in silica gel [Na-SG(I)]5 in place of lump
sodium or sodium sand to reduce aliphatic esters.
Significantly improved Bouveault-Blanc conditions for ester
reduction have been developed using sodium in silica gel
(Na-SG), a free-flowing powder that can be easily handled
in the open atmosphere. Primary alcohols were prepared in
excellent yield from a variety of aliphatic esters under mild
reaction conditions. The chemistry presented here is far safer
than the classic Bouveault-Blanc reduction and is competi-
tive with more modern hydride reduction methods.
We found that by adding the substrate ester 1 to a mixture
of Na-SG(I) in THF at 0 °C followed by the dropwise addition
of methanol, primary alcohols 2 were formed in excellent yields
(Table 1).
Similar to other Bouveault-Blanc reductions, the methanol
could be replaced by a variety of alcohols, including ethanol
and tert-amyl alcohol; however, the conditions described above
were found to be optimal for most aliphatic ester substrates. In
most cases, esters 1 were transformed to alcohols 2 completely
after the addition of methanol was complete (5-10 min).
Additionally, most alcohols 2 were obtained in high purity after
a simple aqueous workup without the need for further purifica-
tion.6
Carboxylic acids were not reduced under these conditions
(Table 1, entry 1). Alkyl substitution was tolerated very well
for phenylacetate esters 1 as substituents on the aromatic ring
(Table 1, entries 3 and 4) and at the R-position (Table 1, entries
13-15). Other aromatic functional groups that were tolerated
included -OH (Table 1, entry 5), -OR (Table 1, entry 6), and
-NR2 (Table 1, entry 7).
Before the advent of widely available hydride reagents,
reduction of esters to primary alcohols was generally performed
with alkali metals in ethanol, the Bouveault-Blanc reduction.1
Because of hazards associated with alkali metal handling and
the vigorous reaction conditions (typically refluxing toluene or
xylene), this process has been largely replaced by the use of
metal hydrides such as lithium aluminum hydride (LAH) or
sodium borohydride. This paper describes an improvement upon
the classic Bouveault-Blanc procedure that utilizes stabilized
alkali metals to prepare primary alcohols from aliphatic esters
in high yield (Figure 1). The mild reaction conditions, simple
aqueous workup, and quick reaction times required make this
updated method competitive with more modern methods of ester
reduction.
Classical Bouveault-Blanc reductions are typically performed
using one of two procedures. In one method, the substrate to
be reduced is dissolved in alcohol and sodium metal is added
rapidly to the solution.2 The second method begins with sodium
in an inert solvent such as toluene, to which the substrate is
added rapidly as a solution in alcohol.3 In both cases, it is
important to mix the sodium and the alcohol as fast as possible
or the reaction fails to achieve complete conversion of the ester
(4) (a) Shatnawi, M.; Paglia, G.; Dye, J. L.; Cram, K. C.; Lefenfeld, M.;
Billinge, S. J. L. J. Am. Chem. Soc. 2007, 129, 1386–1392. (b) Dye, J. L.; Cram,
K. D.; Urbin, S. A.; Redko, M. Y.; Jackson, J. E.; Lefenfeld, M. J. Am. Chem.
Soc. 2005, 127, 9338–9339. (c) Nandi, P.; Redko, M. Y.; Petersen, K.; Dye,
J. L.; Lefenfeld, M.; Vogt, P. F.; Jackson, J. E. Org. Lett. 2008, 10, 5441–5444.
(5) SiGNa Chemistry has developed three categories of alkali metals in silica
gel (M-SG): Stage 0 materials are strongly reducing pyrophoric powders; stage
I materials are nonpyrophoric, free-flowing, black powders that have applications
in organic syntheses; stage II materials have the least reducing capability but
react with water to form hydrogen. All three categories of M-SG are available
commercially.
(1) (a) Chablay, E. Compt. Rend 1913, 156, 1020–1022. (b) Bouveault, L.;
Blanc, G. Bull. Soc. Chim. Fr. 1904, 31, 666–672. (c) Bouveault, L.; Blanc, G.
Compt. Rend. 1903, 136, 1676–1678. (d) Palfray, L.; Anglaret, P. Compt. Rend.
1947, 224, 404–406.
(2) (a) Adkins, H.; Gillespie, R. H. Org. Synth. 1949, 29, 80. (b) Reid, E. E.;
Cockerille, F. O.; Meyer, J. D., Jr.; Cox, W. M.; Ruhoff, J. R. Org. Synth. 1935,
15, 51. (c) Manske, R. H. Org. Synth. 1934, 14, 20.
(6) Upon the addition of water, hydrogen gas is evolved and sodium silicates
are formed. The sodium silicates remain dissolved in the aqueous layer during
workup.
(3) (a) Shriner, R. L.; Ruby, P. R. Org. Synth. 1953, 33, 76. (b) Ford, S. G.;
Marvel, C. S. Org. Synth. 1930, 10, 62.
2598 J. Org. Chem. 2009, 74, 2598–2600
10.1021/jo802778z CCC: $40.75 2009 American Chemical Society
Published on Web 02/16/2009