Abstract
This protocol describes a practical laboratory-scale method for aerobic oxidation of primary alcohols to aldehydes, using a chemoselective CuI/TEMPO (TEMPO = 2,2,6,6-tetramethyl-1-piperidinyloxyl) catalyst system. The catalyst is prepared in situ from commercially available reagents, and the reactions are performed in a common organic solvent (acetonitrile) with ambient air as the oxidant. Three different reaction conditions and three procedures for the isolation and purification of the aldehyde product are presented. The oxidations of eight different alcohols, described here, include representative examples of each reaction condition and purification method. Reaction times vary from 20 min to 24 h, depending on the alcohol, whereas the purification methods each take about 2 h. The total time necessary for the complete protocol ranges from 3 to 26 h.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Corey, E.J. & Suggs, J.W. Pyridinium chlorochromate. An efficient reagent for oxidation of primary and secondary alcohols to carbonyl compounds. Tetrahedron Lett. 16, 2647–2650 (1975).
Piancatelli, G., Scettri, A. & D'Auria, M. Pyridinium chlorochromate: a versatile oxidant in organic synthesis. Synthesis 245–258 (1982).
Luzzio, F.A. & Guziec, F.S. Recent applications of oxochromium-amine complexes as oxidants in organic synthesis. A review. Org. Prep. Proc. Int. 20, 533–584 (1988).
Fatiadi, A.J. Active manganese dioxide oxidation in organic chemistry. Part I. Synthesis 65–104 (1976).
Taylor, R.J.K., Reid, M., Foot, J. & Raw, S.A. Tandem oxidation processes using manganese dioxide: discovery, applications, and current studies. Acc. Chem. Res. 38, 851–869 (2005).
Pfitzner, K.E. & Moffatt, J.G. A new and selective oxidation of alcohols. J. Am. Chem. Soc. 85, 3027–3028 (1963).
Mancuso, A.J., Brownfain, D.S. & Swern, D. Structure of the dimethyl sulfoxide-oxalyl chloride reaction product. Oxidations of heteroaromatic and diverse alcohols to carbonyl compounds. J. Org. Chem. 44, 4148–4150 (1979).
Tidwell, T.T. Oxidation of alcohols by activated dimethyl sulfoxide and related reactions: an update. Synthesis 857–870 (1990).
Dess, D.B. & Martin, J.C. Readily accessible 12-I-5 oxidant for the conversion of primary and secondary alcohols to aldehydes and ketones. J. Org. Chem. 48, 4155–4156 (1983).
Uyanik, M. & Ishihara, K. Hypervalent iodine-mediated oxidation of alcohols. Chem. Commun. 2086–2099 (2009).
Ley, S.V., Norman, J., Griffith, W.P. & Marsden, S.P. Tetrapropylammonium perruthenate, Pr4N+RuO4−, TPAP: a catalytic oxidant for organic synthesis. Synthesis 639–666 (1994).
Sheldon, R.A., Arends, I.W.C.E., Ten Brink, G.-J. & Dijksman, A. Green, catalytic oxidations of alcohols. Acc. Chem. Res. 35, 774–781 (2002).
Zhan, B.-Z. & Thompson, A. Recent developments in the aerobic oxidation of alcohols. Tetrahedron 60, 2917–2935 (2004).
Mallat, T. & Baiker, A. Oxidation of alcohols with molecular oxygen on solid catalysts. Chem. Rev. 104, 3037–3058 (2004).
Stahl, S.S. Palladium oxidase catalysis: selective oxidation of organic chemicals by direct dioxygen-coupled turnover. Angew. Chem. Int. Ed. 43, 3400–3420 (2004).
Markó, I.E. et al. Efficient, ecologically benign, aerobic oxidation of alcohols. Adv. Inorg. Chem. 56, 211–240 (2004).
Schultz, M.J. & Sigman, M.S. Recent advances in homogeneous transition metal-catalyzed aerobic alcohol oxidations. Tetrahedron 62, 8227–8241 (2006).
Gligorich, K.M. & Sigman, M.S. Recent advancements and challenges of palladiumII-catalyzed oxidation reactions with molecular oxygen as the sole oxidant. Chem. Commun. 3854–3867 (2009).
Semmelhack, M.F., Schmid, C.R., Cortés, D.A. & Chou, C.S. Oxidation of alcohols to aldehydes with oxygen and cupric ion, mediated by nitrosonium ion. J. Am. Chem. Soc. 106, 3374–3376 (1984).
Ragagnin, G., Betzemeier, B., Quici, S. & Knochel, P. Copper-catalysed aerobic oxidation of alcohols using fluorous biphasic catalysis. Tetrahedron 58, 3985–3991 (2002).
Gamez, P., Arends, I.W.C.E., Sheldon, R.A. & Reedijk, J. Room temperature aerobic copper–catalysed selective oxidation of primary alcohols to aldehydes. Adv. Synth. Catal. 346, 805–811 (2004).
Kumpulainen, E.T.T. & Koskinen, A.M.P. Catalytic activity dependency on catalyst components in aerobic copper–TEMPO oxidation. Chem. Eur. J. 15, 10901–10911 (2009).
Markó, I.E., Giles, P.R., Tsukazaki, M., Brown, S.M. & Urch, C.J. Copper-catalyzed oxidation of alcohols to aldehydes and ketones: an efficient, aerobic alternative. Science 274, 2044–2046 (1996).
Hoover, J.M. & Stahl, S.S. Highly practical copper(I)/TEMPO catalyst system for chemoselective aerobic oxidation of primary alcohols. J. Am. Chem. Soc. 133, 16901–16910 (2011).
Bandna, B., Aggarwal, N. & Das, P. Solid-supported Pd(0): an efficient heterogeneous catalyst for aerobic oxidation of benzyl alcohols into aldehydes and ketones. Tetrahedron Lett. 52, 4954–4956 (2011).
González-Núñez, M.E., Mello, R., Olmos, A., Acerete, R. & Asensio, G. Oxidation of alcohols to carbonyl compounds with CrO3·SiO2 in supercritical carbon dioxde. J. Org. Chem. 71, 1039–1042 (2006).
Hodgson, D.M., Bray, C.D. & Kindon, N.D. Enamines from terminal epoxides and hindered lithium amides. J. Am. Chem. Soc. 126, 6870–6871 (2004).
Huang, L., Jiang, H., Qi, C. & Liu, X. Copper-catalyzed intermolecular oxidative [3 + 2] cycloaddition between alkenes and anhydrides: a new synthetic approach to γ-lactones. J. Am. Chem. Soc. 132, 17652–17654 (2010).
Acknowledgements
We thank Buzz Meade Photography for photographs in Figures 2 and 3. We are grateful to the US National Institutes of Health (NIH) (RC1-GM091161), the American Chemical Society Green Chemistry Institute Pharmaceutical Roundtable and the National Science Foundation (NSF) (Graduate Research Fellowship for J.E.S.). NMR spectroscopy facilities were partially supported by the NSF (CHE-9208463) and NIH (S10 RR08389).
Author information
Authors and Affiliations
Contributions
J.M.H. developed the catalyst system described here and performed the experimental work described here. J.E.S. confirmed the reproducibility of experimental procedures and performed the oxidation reaction and product characterization for Table 1 (entry 3). S.S.S. conceived and supervised the project. Manuscript assembly was completed by J.M.H., with assistance by J.E.S. and S.S.S.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Supplementary information
Supplementary Methods
Detailed procedure for 10 mmol scale oxidation reaction. (PDF 94 kb)
Supplementary Figure 1
Influence of added H2O on the oxidation of benzyl alcohol by CuI/TEMPO. (PDF 247 kb)
Rights and permissions
About this article
Cite this article
Hoover, J., Steves, J. & Stahl, S. Copper(I)/TEMPO-catalyzed aerobic oxidation of primary alcohols to aldehydes with ambient air. Nat Protoc 7, 1161–1166 (2012). https://doi.org/10.1038/nprot.2012.057
Published:
Issue Date:
DOI: https://doi.org/10.1038/nprot.2012.057
This article is cited by
-
Copper Pyrithione (CuPT)-Catalyzed Oxidation of Secondary and Primary Benzyl Alcohols with Molecular oxygen or Air Under Mild Conditions
Catalysis Letters (2023)
-
Copper(II)-Ethanolamine Triazine Complex on Chitosan-Functionalized Nanomaghemite for Catalytic Aerobic Oxidation of Benzylic Alcohols
Catalysis Letters (2021)
-
Aerobic alcohol oxidation catalyzed by CuO-rectorite/TEMPO in water
Research on Chemical Intermediates (2019)
-
Aerobic Oxidation of Alcohols Catalysed by Cu(I)/NMI/TEMPO System and Its Mechanistic Insights
Catalysis Letters (2018)
-
High-valent copper in biomimetic and biological oxidations
JBIC Journal of Biological Inorganic Chemistry (2017)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.