Oxidation of alcohols to carbonyl compounds with CrO3· SiO2 in supercritical carbon dioxide

Article abstract of DOI:10.1021/jo052137j

Supercritical carbon dioxide (scCO₂) is an effective reaction medium to perform the oxidation of primary and secondary aliphatic alcohols to the corresponding carbonyl compounds with chromium trioxide supported on silica. These reactions were performed by flowing a solution of the alcohol in scCO₂ through a column containing the supported reagent and recovering the product by depressurization. This method avoids the use of organic solvents and the contamination of the products with chromium species.

Full text of DOI:10.1021/jo052137j

Oxidation of Alcohols to Carbonyl Compounds with CrO ‚SiO in
3
2
Supercritical Carbon Dioxide
Mar ´ı a Elena Gonz a´ lez-N u´ n˜ ez, Rossella Mello, Andrea Olmos, Rafael Acerete, and
Gregorio Asensio*
Departamento de Qu ´ı mica Org a´ nica, UniVersidad de Valencia, AVda. V. Andr e´ s Estell e´ s s/n,
4
6100-Burjassot (Valencia), Spain
gregorio.asensio@uV.es
ReceiVed October 13, 2005
Supercritical carbon dioxide (scCO
and secondary aliphatic alcohols to the corresponding carbonyl compounds with chromium trioxide
supported on silica. These reactions were performed by flowing a solution of the alcohol in scCO through
2
) is an effective reaction medium to perform the oxidation of primary
2
a column containing the supported reagent and recovering the product by depressurization. This method
avoids the use of organic solvents and the contamination of the products with chromium species.
Introduction
Several methods have been proposed to improve the reaction
conditions and isolation of the products. A common approach
involves the use of chromium(VI) reagents supported on an inert
The oxidation of primary and secondary alcohols (1) to
aldehydes and ketones (2) is a fundamental reaction in organic
4
,5
matrix,
alumina,
(PVPDC).
such as Cr(VI) species supported on silica or
1
4d-q,s,t,x,y
synthesis. Traditionally, such transformations have been per-
or dichromate supported on polyvinylpyridine
With these reagents, isolation of the reaction
5
e,f
formed with stoichiometric inorganic oxidants, notably, chro-
mium(VI) reagents.2 The use of hazardous chromium(VI)
species in chemical processes poses serious environmental risks
associated with the use of large amounts of chlorinated or
aromatic solvents, which have a considerable life-cycle impact,
and the processing of waste mixtures of heavy metals and
contaminated solvents, which is costly and must be done
properly. Contamination of the reaction products with high-
valent chromium species prevents the further application of this
chemical methodology to the preparation of pharmaceuticals,
cosmetics, or food additives. These economic and environmental
concerns have prompted intense research to develop greener
and more atom-efficient methods that employ clean oxidants
(4) (a) Heravi, M. M.; Hydarzadeh, F.; Farhangi, Y.; Ghassemzadeh,
M. Phosphorus, Sulfur Silicon Relat. Elem. 2004, 179, 1473. (b) Heravi,
M. M.; Hydarzadeh, F.; Farhangi, Y.; Ghassemzadeh, M. J. Chem. Res.
2004, 2, 137. (c) Heravi, M. M.; Farhangi, N.; Beheshtiha, Y. S.;
Ghassemzadeh, M.; Tabar-Hydar, K. Indian J. Chem., Sect. B: Org. Chem.
Incl. Med. Chem. 2004, 43, 430. (d) Heravi, M. M.; Ajami, D.; Shoar, R.
H.; Sarmad, N.; Faridbod, F. Phosphorus, Sulfur Silicon Relat. Elem. 2004,
179, 2423. (e) Gruttadauria, M.; Liotta, L. F.; Deganello, G.; Noto, R.
Tetrahedron 2003, 59, 4997. (f) Ali, M. H.; Wiggin, C. J. Synth. Commun.
2001, 31, 3383. (g) Ali, M. H.; Wiggin, C. J. Synth. Commun. 2001, 31,
1
389. (h) Bendale, P. M.; Khadilkar, B. M. Synth. Commun. 2000, 30, 665.
(i) Taybakhsh, M.; Ghaemi, M.; Sarabi, S.; Ghassemzadeh, M.; Heravi, M.
M. Monatsh. Chem. 2000, 131, 1213. (j) Borkar, S. D.; Khadilkar, B. M.
Synth. Commun. 1999, 29, 4295. (k) Baptistella, L. H.; Sousa, I. M. O.;
Gushikem, Y.; Aleixo, A. M. Tetrahedron Lett. 1999, 40, 2695. (l) Heravi,
M. M.; Ajami, D.; Ghassemzadeh, M. Synthesis, 1999, 3, 393. (m) Heravi,
M. M.; Ajami, D.; Ghassemzadeh, M. Synth. Commun. 1999, 29, 781. (n)
Heravi, M. M.; Ajami, D.; Tabar-Heydar, K. Monatsh. Chem. 1999, 130,
337. (o) Varma, R. S.; Saini, R. K. Tetrahedron Lett. 1998, 39, 1481. (p)
Bendale, P. M.; Khadilkar, B. M. Tetrahedron Lett. 1998, 39, 5867. (q)
Khadilkar, B.; Chitnavis, A.; Khare, A. Synth. Commun. 1996, 26, 205. (r)
Nakamura, H.; Matsuhashi, H. Bull. Chem. Soc. Jpn. 1995, 68, 997. (s)
Hirano, M.; Kobayashi, T.; Morimoto, T. Synth. Commun. 1994, 24, 1823.
(t) Hirano, M.; Kuroda, H.; Morimoto, T. Bull. Chem. Soc. Jpn. 1990, 63,
2433. (u) Cheng, Y. S.; Liuand, W. L.; Chen, S. Synthesis, 1980, 223. (v)
Flatt, S. J.; Fleet, G. W. J.; Taylor, B. J. Synthesis, 1979, 815. (w)
Santaniello, E.; Ponti, F.; Manzocchi, A. Synthesis 1978, 534. (x) Singh,
R. P.; Subbarao, H. N.; Dev, S. Tetrahedron 1978, 35, 1789. (y) San Filippo,
J. Jr.; Chern, C.-I. J. Org. Chem. 1977, 42, 2182.
3
to perform this transformation. However, chromium(VI) re-
agents still remain among the most efficient oxidants for
performing these reactions and are still widely used in the
production of fine chemicals.
(
1) Hudlicky, M. Oxidations in Organic Chemistry; American Chemical
Society: Washington, DC, 1990.
2) Cainelli, G.; Cardillo, G. Chromium Oxidations in Organic Chemistry;
Springer: Berlin, 1984.
3) (a) Sheldon, R. A.; Arends, W. C. E.; Brink, G.-J. T.; Dijksman, A.
(
(
Acc. Chem. Res. 2002, 35, 774. (b) Hoelderich, W. F.; Kollmer, F. Pure
Appl. Chem. 2000, 72, 1273. (c) Sanderson, W. R. Pure Appl. Chem. 2000,
7
2, 1289.
1
0.1021/jo052137j CCC: $33.50 © 2006 American Chemical Society
Published on Web 01/06/2006
J. Org. Chem. 2006, 71, 1039-1042
1039

Gonz a´ lez-N u´ n˜ ez et al.
product requires filtration of the reaction mixture to separate
the reduced chromium reagent and then evaporation of the
solvent. However, despite the considerable improvements in the
reaction conditions that these methods achieve, they do not avoid
the use of organic solvents or contamination of the product with
chromium species detached from the solid support under these
reaction conditions. Contamination also extends to the equip-
ment used to perform the reactions that, in the case of large-
scale preparative work, requires additional cleaning operations.
Supercritical carbon dioxide (scCO2), which has readily
accessible critical conditions (Tc) 31.0 °C, Pc ) 73.8 bar), a
truly benign character, and low cost, is a frequently discussed
FIGURE 1. Anchoring of chromate on the silica support.
lead to the formation of R-chromia (Cr O ), and the reagent
2
3
loses its reactivity in the oxidation of alcohols.
Prior to oxidations in scCO , the supported reagent was
2
4
e
assayed under standard reaction conditions to compare the
results obtained in each case. The reactions were carried out
by treating d-CrO ‚SiO with the corresponding alcohol (1) with
6
alternative reaction medium for chemical synthesis. Further-
3
2
more, there is an existing technology platform for the use of
scCO2 in large-scale applications in both the food and nutrition
industries. These properties have prompted intense research to
further develop the potential of scCO2 as an alternative solvent
for green chemistry.
an initial molar ratio of CrO :ROH 1:1 and a substrate
3
concentration of 0.2 M, in dichloromethane, at room temperature
4
e
for 15 min. The reaction mixture was filtered, and the solid
was thoroughly washed with dichloromethane. In all cases,
evaporation of the organic solvent yielded a pale yellow organic
8
We report here that supercritical carbon dioxide (scCO2) is
an effective reaction medium for the oxidation of primary and
secondary aliphatic alcohols to the corresponding carbonyl
compounds with chromium trioxide supported on silica. The
reactions were performed by flowing a solution of the alcohol
in scCO2 through a column containing the supported reagent
and recovering the product by depressurization. This method
avoids the use of organic solvents and contamination of the
products with chromium species. Handling of the Cr(VI) reagent
under the reaction conditions described here simply involves
placing a suitable polypropylene container charged with the
supported reagent into the column and removing it once the
reaction is complete.
residue. Flame absorption atomic spectroscopy (FAAS) analysis
of the reaction products determined the presence of 45-940
ppm (mg/Kg) of chromium in the reaction products, depending
on the water content of the organic solvent. In all cases, the
recovered solid was dark brown and loose. The results are shown
in Table 1.
The supported reagent d-CrO ‚SiO proved to be very
3
2
effective for performing the oxidation of alcohols to carbonyl
compounds (Table 1). The oxidation reactions did not lead to
any significant overoxidation of the primary aliphatic alcohols
to give the corresponding carboxylic acids. However, this
reagent is less effective in the oxidation of unsaturated alcohols
such as 5-penten-1-ol (1g) or citronellol (1i) (runs 7 and 9, Table
9
1
). Oxidation of the acid-sensitive citronellol (1i) was accom-
Results and Discussion
pained by acid-catalyzed isomerization giving a mixture of
products containing, among others, citronellal (2i), isopulegol,
isopulegone, and rose oxide.
The oxidation of alcohols with d-CrO3‚SiO2 in scCO2 was
carried out by flowing scCO2 (100 g CO2/h) at 220 bar and 40
The reactions were performed with CrO3 deposited on silica
(d-CrO3‚SiO2) that had been prepared by adding silica to an
aqueous solution of chromium trioxide in water and evaporating
the solvent under vacuum.4 The deposition of CrO3 onto the
silica surface yielded an intense orange solid that was dried
under vacuum until constant weight and stored at room
temperature in a desiccator. The Cr(VI) content of the reagent
was determined by redox titration with a 0.1 M aqueous solution
of Fe(NH4)2(SO4). The reagent used in the oxidation reactions
had a range of 1.0-2.0 mmol CrO3/g.
e
°
C for 4 h through a reservoir containing the substrate (2 mmol)
and then through a column packed with the supported reagent
molar ratio of alcohol:CrO3 1:3 in all cases), both placed in a
50-mL reactor (Figure 2). The system was depressurized
(
2
through a micrometric valve, and the reaction products were
collected in a trap cooled with liquid nitrogen. The procedure
is fully described in the Experimental Section. The organic
residues that were recovered after the trap was slowly heated
to room temperature were colorless, and Zeeman absorption
On the basis of the extensive data reported for the Phillips
7
catalysts and given the method of preparation of Cr(VI) on
silica and the loading of the reagent, the Cr(VI) anchored on
the supported reagent should have mainly a polychromate chain
structure bonded to the silanol groups at the silica surface
through the terminal chromate units (Figure 1). Upon calcination
at temperatures higher than 100 °C, the polychromate chains
8
atomic spectroscopy (ZAAS) analysis of the samples indicated
a chromium content of 0.8-1.7 ppb (µg/Kg). The solid reagent
in the column was dark brown and showed a loose appearance.
The results are shown in Table 1.
The oxidation of alcohols 1 with d-CrO3‚SiO2 in scCO2 was
very efficient, and the corresponding carbonyl compounds 2
were obtained in good yields and without any significant
contamination with chromium species detached from the sup-
ported reagent. Particularly in the case of substrates 1e and 1f,
which carry electron-withdrawing groups, the reactions were
much more efficient in scCO2 than in solution. Although the
oxidation was also effective for simple allylic alcohols, the
reaction became less efficient for unsaturated alcohols with more
distant double bonds. This characteristic can be attributed to
adsorption of the substrate on the reagent through Lewis acid-
(5) (a) Linares, M. L.; S a´ nchez, N.; Alajar ´ı n, R.; Vaquero, J. J.; AÄ lvarez-
Builla, J. Synthesis 2001, 382. (b) Shiney, A.; Rajan, P. K.; Sreekumar, K.
Indian J. Chem. B 1997, 36B, 769. (c) Peltonen, R. T.; Ekman, K. B.;
Nasman, J. H. Ind. Eng. Chem. Res. 1994, 33, 235. (d) Brunelet, T.;
Jouitteau, C.; Gelbard, G. J. Org. Chem. 1986, 51, 4016. (e) Fr e` chet, J. M.
J.; Darling, P.; Farrall, M. J. J. Org. Chem. 1981, 46, 1728. (f) Fr e` chet, J.
M. J.; Warnock, J.; Farrall, M. J. Org. Chem. 1978, 43, 2618. (g) Cainelli,
G.; Cardillo, G.; Orena, M.; Sandri, S. J. Am. Chem. Soc. 1976, 98, 6737.
(
h) Lee, R. A.; Donald, D. S. Tetrahedron Lett. 1997, 38, 3857.
(6) (a) Leitner, W. Acc. Chem. Res. 2002, 35, 746. (b) Chemical Synthesis
Using Supercritical Fluids; Jessop, P., Leitner, W., Eds. Wiley-VCH:
Weinheim, New York, 1999. (c) McHugh, M.; Krukonis, V. J. Supercritical
Fluid Extraction; Butterworth-Heinemann: Boston, 1994. (d) Wells, S.;
DeSimone, J. M. Angew. Chem., Int. Ed. 2001, 40, 519.
(8) Willard, H. H.; Merritt, L. L., Jr.; Dean, J. A.; Settle, F. A., Jr.
Instrumental Methods of Analysis, 7th ed.l Wadsworth: Belmont, CA 1988.
(9) Corey, E. J.; Suggs, D. W. Tetrahedron Lett. 1975, 31, 2647.
(7) Groppo, E.; Lamberti, C.; Bordiga, S.; Spoto, G.; Zecchina, A. Chem.
ReV. 2005, 105, 115.
1040 J. Org. Chem., Vol. 71, No. 3, 2006

Oxidation of Alcohols to Carbonyl Compounds
TABLE 1. Oxidation of Alcohols (1) to Carbonyl Compounds (2)
with d-CrO3‚SiO2 in Dichloromethane Solution and in scCO2
initial molar ratios CrO3:ROH under these conditions gave lower
conversion of the substrates. For instance, the reaction of
1
-heptanol (1a) in scCO2 at 220 bar and 40 °C with d-CrO3‚
SiO2 with initial molar ratio CrO3:ROH 2:1 gave only a 50%
conversion of the alcohol. It should be noted that contact
between the substrate in scCO2 solution and the solid-supported
oxidant under flow-through conditions is more restricted than
in solution. Thus, by considering the density of scCO2 under
the reaction conditions (0.86 g/mL), the flow of pressurized
scCO2 solution along the column containing the supported
reagent would be roughly 0.85 mL/min, with a residence time
within the supported reagent of ca. 2.5 min. Assuming a
homogeneous concentration of the substrate (2 mmol) in the
total volume of scCO2 that flowed during the experiment (203
mL), the concentration of the substrate would be ca. 0.01 M.
These data suggest that both the formation of the chromate ester
10
and the rate-determining oxidative elimination take place very
efficiently in scCO2, being flow-through, and agree with other
11
data reported on reactions with supported reagents or catalysts
in scCO2. This effect of the solvent can be attributed to the
gain in free energy of the reactants induced by the low solvation
provided by the reaction medium that leads to a lowering of
1
2
the activation barrier of the reaction, particularly when there
is a decrease in the polarity of the reaction system upon going
from the reactants to the transition state.
In this context, the results obtained in the oxidation of the
acid-sensitive citronellol (1i) (run 9, Table 1) also reveal that
the interaction of the substrate with acidic positions on the
supported reagent is stronger in scCO2 than in dichloromethane
solution, leading to a higher incidence of products derived from
acid-catalyzed isomerization of the distant double bond and
cyclization of the reaction intermediates in scCO2 than in
dichloromethane.
On the other hand, a reaction in solution carried out by
flowing 20 mL of a 0.2 M dichloromethane solution of 1a
through a column containing 0.71 g (2 equiv) of d-CrO3‚SiO2
suspended in dichloromethane at room temperature led to an
85% conversion of the substrate to give the corresponding
aldehyde 2a (66%) and carboxylic acid (34%). Overoxidation
of the alcohol under these conditions can be attributed to the
formation of the corresponding hemiacetal by reaction of the
aldehyde with unreacted alcohol throughout the column. This
process is not significant in scCO2, likely as a result of the higher
dilution of the substrate in the reaction medium and the faster
oxidation under these conditions.
a
Determined by GC analysis of the reaction mixture. Only the corre-
sponding aldehydes or ketones (2) were formed, except where indicated.
b
Reactions at rt with an initial molar ratio of ROH:CrO3 1:1.4e c Reaction
at 40 °C and 220 bar with an initial molar ratio of ROH:CrO3 1:3.
Citronellal 79%, isopulegol 12%. Citronellal 59%, rose oxide 22%,
isopulegone 15%, isopulegol 4%. Phenylacetaldehyde 79%, benzaldehyde
1%. Phenylacetaldehyde 57%, benzaldehyde 43%.
d
e
f
g
1
The pressure and the temperature influence the efficiency of
the reaction in scCO2. Thus, the reaction of 1-heptanol (1a) with
2
equiv of d-CrO3‚SiO2 at 160 and 220 bar and 40 °C with a
flow of 24 g CO2/h gave heptanal (2a) in respective yields of
1% and 53%. This result was not unexpected, since in fixed
bead flow reactors an increase in pressure at constant flow and
temperature results in a longer residence time of the substrate
over the supported reagent. However, by increasing the tem-
perature from 40 to 60 °C at 220 bar, the conversion decreased
to 34%, and this could be related to changes in the solubility of
the substrate in scCO2 or changes in the reactivity of the
supported reagent at higher temperatures.
FIGURE 2. Schematic view of the apparatus used in the oxidation
reactions: (A) CO cylinder; (B) diaphragm pump; (C) substrate
reservoir; (D) column charged with d-CrO ‚SiO ; (E) micrometric valve;
F) trap.
2
2
3
2
(
base association of the π-system with the Cr(VI) species on
the silica surface. This interaction would hinder the approach
of the hydroxyl group to the reactive metal species to form the
chromate ester that is required for the oxidation reaction to take
10
place. Significantly, the incidence of acid-catalyzed processes
was higher in scCO2 than in dichloromethane solution.
The reaction temperature and initial molar ratio were 40 °C
and CrO3:ROH 3:1 for reactions in scCO2. The use of lower
(11) (a) Qian, J.; Timko, M. T.; Allen, A. J.; Russell, C. J.; Winnik, B.;
Buckley, B.; Steinfeld, J. I.; Tester, J. W. J. Am. Chem. Soc. 2004, 126,
5
465. (b) DeSimone, J.; Selva, M.; Tundo, P. J. Org. Chem. 2001, 66, 4047.
(c) Kainz, S.; Brinkmann, A.; Leitner, W.; Pfaltz, A. J. Am. Chem. Soc.
1
999, 121, 6421.
(
10) Carey, F. A.; Sundberg, R. J. AdVanced Organic Chemistry Part B,
(12) Reichardt, C. SolVents and SolVent Effects in Organic Chemistry,
4
th ed.l Plenum Press: New York, 2002.
2nd ed.; VCH: Weinheim, Germany, 1988.
J. Org. Chem, Vol. 71, No. 3, 2006 1041

Gonz a´ lez-N u´ n˜ ez et al.
The oxidation reactions were also examined with other
The high-pressure equipment consisted of a 250-mL AISI 316
stainless steel jacketed reactor, with a high-pressure micrometric
valve placed at the outlet of the reactor, a diaphragm pump (Orlita
MHS 30/8) with a maximum theoretical flow of 8.44 L/h of liquid
alternative supported reagents, namely, polyvinylpyridine dichro-
mate (PVPDC)5e,f and a silica-supported reagent g-CrO3‚SiO2,
which was prepared4q by grinding chromium trioxide with silica
CO
ature probes, and security rupture-disks suitably placed to control
the flow of CO along the system.
2
, and a set of HIP high-pressure valves, pressure and temper-
gel followed by heating at 100 °C for 4 h. These reagents were
less efficient than d-CrO3‚SiO2 in the oxidation of alcohols under
both conventional conditions and in scCO2.
2
The FAAS and ZAAS analyses of chromium were performed
on Unicam939 AA and Perkin-Elmer 4100ZL atomic spectrometers,
respectively. The samples were prepared by evaporating the reaction
products under vacuum and treating the dried residue with 5 mL
of ultrapure water under sonication for 30 min. The glassware used
to recover the reactions products was previously washed with an
aqueous solution of EDTA and then with ultrapure water. The blank
sample for the reactions in solution was prepared by evaporating
dichloromethane and dissolving the residue in ultrapure water under
Thus, the oxidation of alcohols 1 with PVPDC in n-hexane
required longer reaction times (30 min to 8 h), a higher initial
molar ratio of Cr2O72 :ROH (5:1), and higher temperatures (50-
-
6
0 °C) to achieve results similar to those reported above. The
resin that was recovered after the reaction was complete was
dark brown and had a viscous appearance. The oxidation of
some representative alcohols with PVPDC in scCO2 under
continuous-flow conditions failed to achieve any significant
conversion of the starting materials.
sonication. For reactions in scCO
ultrapure water. The spectrometers were calibrated with standardized
aqueous solutions of CrCl prior to the quantitative analysis.
Oxidation of Alcohols 1 with d-CrO ‚SiO in Solution.
General Procedure. To a suspension of 1 g of d-CrO ‚SiO (2
2
, the blank sample consisted of
The reactions with g-CrO3‚SiO2 in dichloromethane solution
3
were more efficient than those with PVPDC and required 30-
3
2
9
0 min at room temperature to achieve the maximum conver-
3
2
sion. Correspondingly, this reagent was less efficient than
d-CrO3‚SiO2 in the oxidation of representative alcohols in
scCO2. The solid recovered from the column was dark brown,
with a loose appearance in most cases but viscous in the case
of unsaturated substrates. Formation of this material on the
surface of the reagent proved to be inconvenient for performing
the reactions in scCO2, since the viscous layer covers the most
accessible regions of the reactive surface at the initial stages of
the reaction and prevents the flow of scCO2 to penetrate into
the inner matrix of the support. In fact, the solid that was
recovered after the reaction was complete was inhomogeneous,
with a viscous dark-brown external surface and an inner part
consisting of unreacted material.
mmol) in 10 mL of dichloromethane at room temperature was added
the corresponding alcohol 1 (2 mmol) in a single step. After 15
min, the reaction mixture was analyzed by GC and showed complete
conversion of the alcohol 1 into the corresponding carbonyl
compound 2. The reaction mixture was filtered, and the solid was
washed with dichloromethane. The solution was dried over
4
anhydrous MgSO , and then the solvent was removed under vacuum
to yield a pale yellow residue. The reaction products were identified
1
13
by H and C NMR spectroscopy.
3 2 2
Oxidation of Alcohols with d-CrO -SiO in scCO . General
Procedure. The alcohol (1 mmol) was placed in a Teflon cylinder
covered at the top with a screw cap with two 1/4-28 UNF threaded
ports. One of the ports of the reservoir was kept open, and the
second was connected through 1/8′′ Teflon tubing and suitable
fittings to a 5-mL Rezorian Luer-lock syringe-tip cartridge (Supelco)
Conclusions
3 2
charged with 1.5 g of d-CrO ‚SiO (3 mmol). The assembly was
Cr(VI) reagents are among the most efficient oxidants for
performing the transformation of alcohols (1) to carbonyl
compounds (2) and are still used in large-scale preparative
processes despite the environmental hazards associated with both
the Cr(VI) species and the organic solvents required for these
reactions. We have shown that supercritical carbon dioxide
placed within the 250-mL autoclave thermostated at 40 °C, and
the outlet of the column was connected through Teflon tubing and
a septum to the outlet of the reactor. The outlet of the high-pressure
micrometric valve was connected to a trap cooled with a liquid
nitrogen bath through 1/8′′ Teflon-tubing. The pressure in the trap
was equilibrated with a flow of nitrogen.
2
The reactor was closed, charged with CO , and then pressurized
(scCO2) is an effective reaction medium for performing the
to 220 bar. This operation usually required ca. 15 min. The stroke
volume of the pump and the aperture of the high-pressure
micrometric valve at the outlet of the reactor were regulated to
achieve steady continuous-flow conditions at 220 bar. The flow of
oxidation of primary and secondary aliphatic alcohols 1 to the
corresponding carbonyl compounds 2 with chromium trioxide
supported on silica (d-CrO3‚SiO2) under continuous-flow condi-
tions. This process avoids the use of organic solvents and
contamination of the reaction products by chromium species
detached from the supported reagent. Handling of the Cr(VI)
reagent is reduced to placing a suitable polypropylene container
charged with the supported material into the column and
removing it once the reaction is complete. This method precludes
the negative environmental impact associated with the use of
Cr(VI) reagents in the oxidation of alcohols to carbonyl
compounds.
CO
meter.
The system was operated for 4 h and then completely depres-
2
at the outlet of the system was monitored with a bubble flow-
surized through the micrometric valve. The trap was allowed to
warm to room temperature. The colorless residue was dissolved in
1
deuterated chloroform and analyzed by GC, GC-MS, and H and
13
C NMR.
Acknowledgment. Financial support from the Spanish
Direcci o´ n General de Investigaci o´ n (BQU2003-00315 and
BQU2001-3005) and Generalitat Valenciana (Grupos 2001-2003
and GV04B-161) is gratefully acknowledged. A.O. thanks the
Spanish Ministerio de Educaci o´ n y Ciencia for a fellowship.
We thank S.C.S.I.E. (UVEG) for access to their instrumental
facilities.
Experimental Section
Solvents were purified by standard procedures. Reagents were
purified by distillation prior to use. The supported reagent d-CrO ‚
3
was prepared4 by mixing a solution of 1 g of CrO
e
SiO
of ultrapure water with 4 g of chromatography-grade silica gel
Merck 230-240 mesh) and evaporating the solvent under vacuum.
The reagent was dried under vacuum until it reached a constant
weight and stored in a desiccator. The supported reagent g-CrO
2
3
in 15 mL
(
Supporting Information Available: Gas chromatograms, con-
ditions, and NMR spectra of the reaction crudes from the oxidation
3
‚
of alcohols 1 with d-CrO
free of charge via the Internet at http://pubs.acs.org.
3
2 2
‚SiO in scCO . This material is available
2 3 2
SiO with SiO , following the
was prepared4 by grinding CrO
q
reported procedure, drying at 100 °C for 4 h, and storing in a
desiccator.
JO052137J
1042 J. Org. Chem., Vol. 71, No. 3, 2006