Selective oxidation of primary alcohols with chromium trioxide under solvent free conditions

Article abstract of DOI:10.1016/S0040-4039(02)01333-3

Selective oxidation of primary alcohols to the corresponding aldehydes by chromium trioxide under solvent free conditions are described. This new oxidation procedure is simple and affords good yields.

Full text of DOI:10.1016/S0040-4039(02)01333-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 6095–6097
Selective oxidation of primary alcohols with chromium trioxide
under solvent free conditions
Ji-Dong Loua,* and Zhi-Nan Xub
aInstitute of Chemical and Biological Technology, New University of Lisbon, 2780 Oeiras, Portugal
bDepartment of Chemical Engineering and Bioengineering, Zhejiang University, Hangzhou, Zhejiang 310027, China
Received 3 July 2002; accepted 4 July 2002
Abstract—Selective oxidation of primary alcohols to the corresponding aldehydes by chromium trioxide under solvent free
conditions are described. This new oxidation procedure is simple and affords good yields. © 2002 Elsevier Science Ltd. All rights
reserved.
The oxidation of primary alcohols to the corresponding
aldehydes is a transformation that is fundamental to
synthetic organic chemistry, and numerous reagents
and methods have been developed to carry out this
important reaction.
drous conditions, since under acidic conditions the
oxidation product and unreacted alcohol will react to
give a hemiacetal that is rapidly oxidised to an ester,
and in aqueous media the aldehyde product can be
hydrated to the geminal diol that will be further
oxidised.
Chromium trioxide (CrO3)-based oxidants are one of
the most widely used of all oxidising reagents for this
transformation.1–4 Over the years they have been con-
tinually developed and modified to overcome the typi-
cal problems that occur during the oxidation and to
accept wider ranges of substrates with improved selec-
tivity. They have been accepted by synthetic chemists
because they are readily available and easy to handle.
However, the most important problem in their oxida-
tions is that overoxidation can occur during the reac-
tion process. In an attempt to circumvent this problem
the trend has been to develop the use of complexes,
supported reagents, and others, such as CrO3–(pyri-
In connection with our recent work on the solvent free
oxidations,25 we now report here that oxidation of
primary alcohols with CrO3 under solvent free condi-
tions is a new system which offers a simple and efficient
selective oxidation method for the preparation of alde-
hydes. In our experiments, the commercial CrO3 with-
out grinding and the 1.5 to 1 molar ratio of CrO3 to
substrate are employed. First oxidant is carefully added
to a portion of the substrate and the mixture is stirred
magnetically until TLC analysis indicates a completed
reaction. Most reactions can be carried out at room
temperature, but for solid substrates the reaction tem-
perature should be near or above their melting points.
In general, the oxidations are complete within 3–8 h.
The reaction mixture is then worked up by filtration
with dichloromethane or diethyl ether assisted by Celite
or silica gel. Distillation of the solvent gives a product
that is of acceptable purity for most purposes. If greater
purity is required, the product can be distilled or recrys-
tallised. The results, which are shown in Table 1, show
that the method is generally applicable to a range of
primary alcohols, and gives the corresponding alde-
hydes in good yields.
dine)2 and CrO3–(3,5-dimethylpyrazole)7 complexes;
5,6
CrO3 supported on resin,8 on graphite,9 on halosi-
lane,10,11 on silica gel,12,13 on aluminium silicate,14 on
kieselguhr,15 and on zirconium(IV) oxide;16 CrO3 with
diethyl ether,17 with crown ether,18 with t-butyl
hydroperoxide,19 and with quaternary ammonium20
species; CrO3 in dimethyl formamide (DMF),21 in hexa-
methylphosphorous triamide (HMPT),22,23 and in
dimethyl sulfoxide (DMSO)24 systems. These proce-
dures are mainly performed in neutral media and anhy-
Keywords: selective oxidation; primary alcohols; aldehydes;
chromium trioxide; solvent free.
In summary, solvent free oxidation using CrO3 as an
oxidant is a new and efficient method for selective
oxidation of primary alcohols.
* Corresponding
lou@itqb.unl.pt
author.
Fax:
+351-21-44-03-609;
e-mail:
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01333-3

6096
J.-D. Lou, Z.-N. Xu / Tetrahedron Letters 43 (2002) 6095–6097
Table 1. Solvent free chromium trioxide oxidations
Caution: CrO3 is a highly toxic agent. All chromi-
um(VI) reagents must be handled with care. The muta-
genicity of chromium(VI) compounds is well
documented.26 Special care must always be exercised in
adding CrO3 to organic media. This oxidation is
exothermic, and precautions should be taken to avoid it
running amuck. Even though we have run each reaction
at least three times on the amounts ranging from 0.100
to 0.300 g without encountering any problem, we never-
theless advise that any user should certainly never run
on a large scale.
sis; Trost, B. M.; Fleming, I., Eds.; Pergamon Press:
London, 1991; Vol. 7, pp. 251–289.
5. Poos, G. I.; Arth, G. E.; Beyler, R. E.; Sarett, L. H. J.
Am. Chem. Soc. 1953, 75, 422.
6. Holum, J. R. J. Org. Chem. 1961, 26, 4814.
7. Corey, E. J.; Fleet, G. W. J. Tetrahedron Lett. 1973, 14,
4499.
8. Cainelli, G.; Cardillo, G.; Orena, M.; Sandri, S. J. Am.
Chem. Soc. 1976, 98, 6737.
9. Lalancette, J.-M.; Rollin, G.; Dumas, P. Can. J. Chem.
1972, 50, 3058.
10. Aizputua, J. M.; Palomo, C. Tetrahedron Lett. 1983, 24,
4367.
References
11. Aizputua, J. M.; Juaristi, M.; Lecea, B.; Palomo, C.
Tetrahedron 1985, 41, 2903.
1. Fieser, L. F.; Fieser, M. Reagents for Organic Synthesis;
John Wiley and Sons: New York, 1967; Vol. 1, pp.
144–147 and subsequent volumes in the series.
12. Santaniello, E.; Ponti, F.; Manzocchi, A. Synthesis 1978,
534.
13. Lou, J.-D.; Wu, Y.-Y. Chem. Ind. (London) 1987, 531.
14. Lou, J.-D.; Wu, Y.-Y. Synth. Commun. 1987, 17, 1717.
15. Lou, J.-D. Synth. Commun. 1989, 19, 1841.
16. Nakamura, H.; Matsuhashi, H. Bull. Chem. Soc. Jpn.
1995, 68, 997.
17. Flatt, S. J.; Fleet, G. W. J.; Taylor, B. J. Synthesis 1979,
815.
18. Ganboa, L.; Aizpurua, J. M.; Palomo, C. J. Chem. Res.
2. Freeman, F. In Organic Synthesis by Oxidation with
Metal Compounds; Mijs, W. J.; de Jonge, C. R. H. I.,
Eds.; Plennum Press: New York, 1986; pp. 68–81.
3. Haines, A. H. Methods for the Oxidation of Organic
Compounds, Alcohols, Alcohol Derivatives, Alkyl Halides,
Nitroalkanes, Alkyl Azides, Carbonyl Compounds,
Hydroxyarenes and Aminoarenes; Academic Press: Lon-
don, 1988; pp. 17–41.
(S) 1984, 92.
4. Ley, S. V.; Madin, A. In Comprehensive Organic Synthe-
19. Muzart, J. Tetrahedron Lett. 1987, 28, 2133.

J.-D. Lou, Z.-N. Xu / Tetrahedron Letters 43 (2002) 6095–6097
6097
20. Brunelet, T.; Jouitteau, C.; Gelbard, G. J. Org. Chem.
1986, 51, 4016.
21. Pfenninger, E.; Poel, D. E.; Berse, C.; Wehrli, H.;
Schaffner, K.; Jeger, O. Helv. Chim. Acta 1968, 51, 772.
22. Cardillo, G.; Orena, M.; Sandri, S. Synthesis 1976,
394.
23. Yoshii, E.; Oribe, T.; Tumura, K.; Koizumi, T. J. Org.
Chem. 1978, 43, 3946.
24. Lou, W.-X.; Lou, J.-D. Synth. Commun. 1992, 22, 767.
25. Lou, J.-D.; Xu, Z.-N. Tetrahedron Lett. 2002, 43, 6149.
26. Cupo, D. Y.; Wetterhahn, K. E. Cancer Res. 1985, 45,
1146.