Organic Process Research & Development 2005, 9, 577−582
Technical Production of Aldehydes by Continuous Bleach Oxidation of Alcohols
Catalyzed by 4-Hydroxy-TEMPO
Elke Fritz-Langhals*
Consortium fu¨r Elektrochemische Industrie GmbH, a subsidiary of Wacker-Chemie GmbH, Zielstattstrasse 20-22,
D-81379 Mu¨nchen, Germany
Scheme 1. Oxidations of alcohols to aldehydes catalyzed by
TEMPO (1)
Abstract:
Aldehydes can be easily prepared from the corresponding
alcohols in good to excellent yields by oxidation with technical
bleach and catalytic amounts of 4-hydroxy-2,2,6,6-tetramethyl-
piperidine-1-oxyl (1b, 4-hydroxy TEMPO, “HOT”). Whereas
the well-known batch process performed on lab scale is not
suitable for the technical synthesis especially of activated
â-substituted aldehydes, this transformation can be performed
continuously in a simple tube reactor. This layout meets all
requirements necessary for the process, i.e., turbulent mixing
of the biphasic mixture, removal of heat, short contact times,
and high output. Thus, a single tube of 3 mm diameter renders
about 60 mol of aldehyde per day.
rochromate,11 is also well-established. The handling of
chromium(VI), however, is crucial due to its toxicity and
the risk of product contamination. Moreover, the selectivity
with functionalized substrates is only modest in many cases.
Mild and selective oxidation reagents have been devel-
oped, for example, activated DMSO,12 Dess Martin perio-
dinane13 or IBX,14,15 and palladium catalyzed air oxidations.16
Their applicability, however, is restricted to transformations
on the lab scale. Therefore, there is still a demand for mild
and selective reagents in modern synthetic chemistry which
are especially prone to industrial application. Catalytic
methods would be most advantageous.
Oxidation of alcohols employing nitroxyl compounds (1),
in particular TEMPO (2,2,6,6-tetramethyl-piperidine-1-oxyl,
1a), as oxidation catalysts seems to be applicable more
generally.17 The catalytic process using sodium hypochlorite
(i.e., bleach) or sodium hypobromite as oxidant was first
developed by Anelli and co-workers18-20 (Scheme 1). Further
oxidants in combination with TEMPO are described in the
recent literature.21-25 The Anelli protocol using bleach,
however, seems to be most attractive because of its high
Introduction
The oxidation of alcohols to aldehydes or ketones is a
fundamental and important transformation in organic
chemistry,1-3 since these compounds having a high reaction
potential are formed from readily available substrates.
Aldehydes are versatile intermediates, e.g., for the asym-
metric synthesis of cyanohydrins,4,5 hydroxy carboxylic
acids,4,5 and amino acids,6 for asymmetric aldol reactions,7
and for Wittig reactions.8 Aldehydes with additional sub-
stituents in â or γ position8 are especially useful as building
blocks in pharmaceutical syntheses. Therefore, the transfor-
mation of alcohols to aldehydes is very interesting to be
performed on industrial scale.
Some industrially employed methods for the synthesis of
aldehydes from the corresponding alcohols are known. Gas-
phase dehydrogenation9 is frequently employed in industry
but is restricted to volatile and thermally stable substrates.
The reaction conditions have to be matched specifically to
each substrate. The oxidation with chromium (VI) oxides,
for example, pyridinium dichromate10 or pyridinium chlo-
(10) Corey, E. J.; Schmidt, G. Tetrahedron Lett. 1979, 399-402.
(11) Piancatelli, G.; Scettri, A.; D’Auria, M. Synthesis 1982, 245-258.
(12) Mancuso, A. J.; Swern, D. Synthesis 1981, 165. Tidwell, T. T. Synthesis
1990, 857-870.
(13) Dess, D. B.; Martin J. C. J. Am. Chem. Soc. 1991, 113, 7277-7287.
(14) Tohma, H.; Kita, Y. AdV. Synth. Catal. 2004, 346, 111-124.
(15) Wirth, T. Angew. Chem., Int. Ed. 2005, 117, 3656-3665.
(16) Reviews: Muzart, J. Tetrahedron 2003, 59, 5789-5816. Stahl, S. S Angew.
Chem., Int. Ed. 2004, 43, 3400-3420. Bagdanoff, J. T.; Stoltz, B. M. Angew.
Chem., Int. Ed. 2004, 43, 353-357.
(17) Reviews: Adam, W.; Saha-Mo¨ller, C. R.; Ganeshpure, P. A. Chem. ReV.
2001, 101, 3499-3548. De Nooy, A. E. J.; Besemer A. C.; van Bekkum,
H. Synthesis 1996, 1153-1174.
(18) Anelli, P. L.; Biffi, C.; Montanari, F.; Quici, S. J. Org. Chem. 1987, 52,
2559-2562.
(19) Anelli, P. L.; Banfi, S.; Montanari, F.; Quici, S. J. Org. Chem. 1989, 54,
2970-2972.
(20) Anelli, P. L.; Montanari, F.; Quici, S. Org. Synth. 1990, 69, 212-219.
(21) Pozzi, G.; Cavazzini, M.; Quici, S.; Benaglia, M.; Dell’Anna, G. Org. Lett.
2004, 6, 441-443.
(22) Kim, S. S.; Jung, H. C. Synthesis 2003, 14, 2135-2137.
(23) Kashiwagi, Y.; Chiba, S.; Junichi, A. New J. Chem. 2003, 27, 1545-1549.
(24) Liu, R.; Liang, X.; Dong, C.; Hu, X. J. Am. Chem. Soc. 2004, 126, 4112-
4113.
* Corresponding author. E-mail: elke.fritz-langhals@wacker.com. Tele-
phone: +49-89 74844227. Fax: +49-89-74844242.
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10.1021/op050040t CCC: $30.25 © 2005 American Chemical Society
Published on Web 08/11/2005
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