Efficient solvent-free iron(III) catalyzed oxidation of alcohols by hydrogen peroxide

Article abstract of DOI:10.1016/S0040-4039(02)02569-8

Selective oxidation of secondary and benzylic alcohols was efficiently accomplished by H₂O₂ under solvent-free condition catalyzed by FeBr₃. Secondary alcohols are selectively oxidized even in the presence of primary ones.

Full text of DOI:10.1016/S0040-4039(02)02569-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 549–552
Efficient solvent-free iron(III) catalyzed oxidation of alcohols by
hydrogen peroxide
Sandra E. Mart´ın* and Anal´ıa Garrone
INIFQC-Dpto. de Qu´ımica Orga´nica, Fac. de Ciencias Qu´ımicas, Universidad Nacional de Co´rdoba, Ciudad Universitaria,
5000-Co´rdoba, Argentina
Received 25 October 2002; revised 12 November 2002; accepted 13 November 2002
Abstract—Selective oxidation of secondary and benzylic alcohols was efficiently accomplished by H2O2 under solvent-free
condition catalyzed by FeBr3. Secondary alcohols are selectively oxidized even in the presence of primary ones. This method is
high yielding, safe and operationally simple. © 2002 Elsevier Science Ltd. All rights reserved.
The oxidation of alcohols plays an important role in
organic synthesis while the development of new oxida-
tive processes continues drawing attention in spite of
the availability of numerous oxidizing reagents.1 Such
oxidizing reagents often used in stoichiometric amounts
are often hazardous or toxic. Hence, in terms of eco-
nomical and environmental concern, catalytic oxidation
processes with inexpensive and environmental oxidants
are extremely valuable. One favorite oxidant to resort
to is hydrogen peroxide due to its environmental
impact, since water is the only by product of such
oxidative reactions.2 Although a variety of different
catalytic systems for the hydrogen peroxide oxidation
of alcohols has been developed,3 there is a growing
interest in the search for new efficient metal catalysts
for this concern. Many molybdenum- and tungsten-
based catalytic systems using hydrogen peroxide have
been reported.4 Additionally, many examples with man-
ganese catalysts and hydrogen peroxide were described.
Manganese-containing polyoxometalate has been used
as an effective catalyst for alcohol oxidation.3b Benzylic
alcohols could be oxidized by a dinuclear mangane-
se(IV) complex.5 The system hydrogen peroxide–man-
ganese(IV) complex transforms secondary alcohols into
their corresponding ketones with good yields at room
temperature.6 Several other systems using aqueous
hydrogen peroxide as the oxidant and metal catalysts
under phase-transfer catalytic conditions have been
reported.7 Noyori has described a tungstate-based
biphasic system using a phase-transfer catalyst,8 a more
effective solvent-free version of the process previously
reported by Venturello.9 Recently, microwave-assisted
oxidation using aqueous hydrogen peroxide and com-
mercially available phase-transfer catalyst was
reported.10 On the other hand, while oxidations by
hydrogen peroxide catalyzed by ferrous ions (Fenton’s
reagent) have been carefully investigated,11 catalyzed
oxidations with Fe(III) have received considerably less
attention. It has been noticed that besides the normal
oxidation of saturated hydrocarbons in Gif-type oxida-
tion reactions, alcohols could be transformed into their
corresponding ketones with good yields using Fe(III)
catalysts and t-butyl hydroperoxide.12 Otherwise,
Fe(III) nitrate catalyzed the oxidation of ethanol with
hydrogen peroxide in a fed-batch reactor.13 On the
other hand, the reaction of Fe(III) porphyrin and non-
porphyrin complexes with H2O2 has been extensively
studied, with the aim of elucidating the mechanisms of
the O–O activation and oxygen atom transfer
reactions.14
Herein, we reported a very efficient and selective oxida-
tion of non-activated secondary alcohols with H2O2
catalyzed by FeBr3, developed under mild conditions
and affording products in high yields. The reaction can
take place under organic-aqueous biphasic conditions
or under organic-solvent-free conditions. The major
advantage of this method apart from the solvent-free
conditions is that it does not require a metal complex
or phase-transfer condition.
The oxidation of alcohols was carried out at room
temperature in the presence of catalytic amounts of
FeBr3 and using H2O2 as oxidant (Eq. (1)) in an
aqueous/organic biphasic system or solvent-free condi-
* Corresponding author. Tel.: +54-351-433-4173; fax: +54-351-433-
3030; e-mail: martins@dqo.fcq.unc.edu.ar
0040-4039/03/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02569-8

550
S. E. Mart´ın, A. Garrone / Tetrahedron Letters 44 (2003) 549–552
tions. Menthol was selected as a model substrate for the
optimization process. A typical experimental procedure
was quite simple: To the FeBr3 (0.2 mmol) in 5 mL of
the organic solvent (or without solvent) was added the
substrate (1 mmol) and then hydrogen peroxide (5
mmol, 30%) was slowly incorporated. The reaction
mixture was stirred at room temperature for 24 hours.
Yields were determined by gas chromatographic assays
using an internal standard. Results are shown in Table
1.
tion with only FeBr3 without any oxidant under the
same conditions resulted in no reaction. No improved
rates could be observed at higher temperatures. The
oxidation reaction was found to be dependent on the
Fe(III) salt. For instance, the use of FeCl3 as catalyst
revealed large differences in the conversion rate of
menthol into menthone (entry 5, Table 1). Oxidation
can also be carried out with the complex
[(FeBr3)2(DMSO)3] (entry 6, Table 1). This complex
was synthesized as previously reported.16 The main
advantage of the use of this coordination compound is
its high stability unlike anhydrous FeBr3, which facili-
tates storage and handling and reacts similarly to
FeBr3.17 The reaction did not occur varying from FeBr3
to KBr (entry 7, Table 1).
(1)
Table 1. Oxidation reaction of menthol to menthone with
hydrogen peroxide as oxidanta
Having established what appeared to be the optimal
conditions, we switched our attention to the substrate.
A series of alcohols was then reacted against this
remarkably simple procedure and the results are present
in Table 2. The catalytic oxidation was carried out at
room temperature using FeBr3 and H2O2 with acetoni-
trile as solvent (System A). Although the oxidation of
menthol carried out under the same conditions without
organic solvent (entry 2, Table 2) was not successful,
interesting results were obtained for the catalytic oxida-
tion with all other alcohols in solvent-free conditions
(System B). Aqueous hydrogen peroxide in the presence
of catalytic amount of FeBr3 without solvent results in
slightly improved rates in the oxidation. This is an
important feature of this catalytic oxidation. Actually,
we have found that there is no need for phase-transfer
reagent, as in the solvent-free oxidations previously
described.8,10
Entry
Catalyst
Solvent
Yieldsb (%)
1
2
3
4
5
6
7
FeBr3
FeBr3
FeBr3
FeBr3
FeCl3
CH3CN
AcOEt
–
CH3CN
CH3CN
CH3CN
CH3CN
92
89
18
72
c
26
[(FeBr3)2(DMSO)3]
74
KBrd
N.R.e
a Reactions were carried out with 1 mmol of the alcohol at room
temperature, with 0.2 mmol of FeBr3 and 5 mmol of 30% aqueous
H2O2 for 24 h.
b Determined by GC.
c Reaction carried out with 0.15 mmol of FeBr3.
d Reaction carried out with only 0.75 mmol of KBr.
e N.R.: reaction did not occur.
The large excess amount of hydrogen peroxide required
is a result of its decomposition in the presence of the
FeBr3 catalyst. The oxygen released in the decomposi-
tion reaction plays no role in the oxidation of alcohols.
No oxidation takes place by performing a reaction
under similar conditions but using oxygen as oxidant.
The first variable examined was the solvent. Previous
work by this group on the aerobic oxidation of alcohols
by Fe(III)15 suggested that CH3CN is likely to be the
solvent of choice for Fe(III) transformations. The sys-
tem consisting of FeBr3 in acetonitrile with H2O2 led to
the efficient oxidation of menthol (92%) within 24
hours (entry 1, Table 1). Yet, other solvents were
examined. The use of AcOEt (entry 2, Table 1) as
solvent yielded similar results as acetonitrile. Other
reaction solvents such as CH2Cl2, MeOH or benzene
were not useful for this reaction, moreover, without
organic solvent the oxidation of menthol was not suc-
cessful (entry 3, Table 1).
As shown, the system FeBr3/H2O2 was found to be
selective, both secondary and benzylic alcohols were
oxidized in good yields. All the reactions occurred with
complete selectivity for ketones or aldehydes and no
other products were detected in the reaction mixture.
The products could be readily isolated. Yields were
confirmed either by gas chromatography using an inter-
nal standard or when products were isolated by column
chromatography with an appropriate combination of
ethyl acetate/hexanes.
The reaction works well with sterically hindered alco-
hols such as menthol (entry 1, Table 2) or 2-adaman-
tanol (entry 3, Table 2). The 2-adamantanol required
longer reaction times for the same conversion rate than
did other cyclic alcohols. The oxidation reactions,
therefore, appear not to be quite sensitive to steric
factors near the alcohol functional group. With these
crystalline alcohols it is necessary to run the reaction
with organic solvent in order to achieve good yields
(entries 1–4, Table 2). The same pattern was observed
in the solvent-free system described by Noyori.8
In order to improve the efficiency of the catalytic
system we examined different ratios among the sub-
strate, the metallic salt and the H2O2. The best results
were found when the ratio substrate:H2O2:FeBr3 was
1:5:0.20. The use of lower amounts of catalyst led to
lower yields (entry 4, Table 1). Control experiments
revealed that in the absence of FeBr3, only less than 1%
of the oxidized product was detected. Attempted oxida-
Many other secondary cyclic alcohols were efficiently
oxidized in both systems (entries 5–8, Table 2). The
catalytic oxidation can also be successfully performed
with aliphatic secondary alcohols (entries 9–12, Table
2). For instance, the oxidation of 2-butanol selectively

S. E. Mart´ın, A. Garrone / Tetrahedron Letters 44 (2003) 549–552
551
Table 2. Oxidation of alcohols with hydrogen peroxide catalyzed by Fe(III) in acetonitrile (System A) or without solvent
(System B)a
provides a general, safe, and simple method for sec-
ondary and benzylic alcohols oxidation. Secondary
alcohols are selectively oxidized even in the presence of
primary ones. The reaction under very mild conditions
is high yielding and easy to implement. An important
advantage of this method aside from the solvent-free
conditions is that it does not require a phase-transfer
catalyst.
gave 2-butanone in 95% yield (entry 10, Table 2). It
should be noticed that simple primary alcohols were
not oxidized to the corresponding carbonyl product
and the starting alcohol was recovered (entry 13, Table
2). Besides, secondary aliphatic alcohols were selectively
oxidized even in the presence of primary ones (entries
14–15, Table 2). Trost4b found the same selectivity in a
molybdenum catalyzed alcohol oxidation by hydrogen
peroxide. Benzylic alcohols behave quite differently
from aliphatic ones and the oxidation of benzyl alcohol
produced benzaldehyde in good yield with no over
oxidation (entries 16–17, Table 2). This behavior is
simple to explain because of the reactivity of benzylic
alcohols. Surprisingly, benzyl alcohol is converted to
benzaldehyde more efficiently in the solvent-free system
than in the other one. Finally, the oxidation of alcohols
to the corresponding carbonyl compounds is well
known to take place by high-valent metal com-
plexes.1a,12 Therefore, the alcohol oxidation with the
system FeBr3/H2O2 could be achieved via high-valent
iron species.
General Procedure. Oxidation Reactions with H2O2 cat-
alyzed by FeBr3. A typical experiment was carried out
in an open reaction tube fitted with a condenser. To the
catalyst FeBr3 (0.20 mmol) in 5 mL of CH3CN (or
solvent-free) menthol was added (1 mmol). Then hydro-
gen peroxide (5 mmol, 30%) was slowly incorporated.
The reaction mixture was stirred at room temperature
for 24 h. GC was used to follow the reaction. When the
reaction was complete, CH2Cl2 was added and both
phases were separated. The aqueous layer was extracted
with CH2Cl2. The combined organic layers were washed
with water, dried over MgSO4, and the solvent was
removed in vacuo. The residue was chromatographed
on a silica gel (70–270 mesh ASTM) column, and eluted
with ethyl acetate/hexanes using various ratios. All
products identified were found to be identical to
authentic samples.
In conclusion, organic-solvent-free oxidation of alco-
hols using aqueous hydrogen peroxide, an ideal oxi-
dant, in the presence of catalytic amounts of FeBr3

552
S. E. Mart´ın, A. Garrone / Tetrahedron Letters 44 (2003) 549–552
ki, J.; Aoki, M.; Noyori, R. Tetrahedron Lett. 1998, 39,
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Provincia de Co´rdoba (CONICOR), for financial
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