Highly efficient oxidation of benzyl alcohols using the catalytic system sulfoxide/oxo-complexes

Article abstract of DOI:10.1016/j.tetlet.2012.08.145

This work reports a novel and highly efficient method for the oxidation of benzyl alcohols to the corresponding aldehydes catalyzed by HReO₄ (5 mol %) using 4-methylphenyl sulfoxide as the oxidizing agent.

Full text of DOI:10.1016/j.tetlet.2012.08.145

Tetrahedron Letters 53 (2012) 6205–6208
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Tetrahedron Letters
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Highly efficient oxidation of benzyl alcohols using the catalytic system
sulfoxide/oxo-complexes
⇑
Sara C. A. Sousa, Joana R. Bernardo, Ana C. Fernandes
Centro de Química Estrutural, Instituto Superior Técnico, Universidade Técnica de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal
a r t i c l e i n f o
a b s t r a c t
Article history:
This work reports a novel and highly efficient method for the oxidation of benzyl alcohols to the corre-
Received 14 June 2012
Revised 28 August 2012
Accepted 31 August 2012
Available online 8 September 2012
sponding aldehydes catalyzed by HReO
4
(5 mol %) using 4-methylphenyl sulfoxide as the oxidizing agent.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Oxidation
Benzyl alcohols
Aldehydes
Oxo-complexes
Sulfoxides
The synthesis of aldehydes is a fundamental process in Organic
Chemistry, in particular, for the chemical and pharmaceutical
industries, where aldehydes find wide applications as intermedi-
ates. The Swern oxidation (using DMSO coupled with the electro-
phile oxalyl chloride) is an efficient and widely used method for
the oxidation of alcohols.1 However, these reagents bring some
disadvantages: the by-product dimethyl sulfide is volatile (bp
cation we report the selective oxidation of benzyl alcohols to the
corresponding aldehydes catalyzed by oxo-complexes using a sulf-
oxide as the oxidizing agent.
Initially we investigated the oxidation of 4-nitrobenzyl alcohol
4 2 2 2 2
with the oxo-complexes HReO , MoO (acac) , MoO Cl , VO(acac)2,
,2
and WO Cl via oxygen transfer from a sulfoxide. The reactions
2
2
were carried out in refluxing toluene under air atmosphere (Ta-
3
7 °C) and has an unpleasant smell; the electrophile oxalyl chlo-
ble 1), and the progress of the oxidations was monitored by thin
1
ride is moisture sensitive, toxic and its vapor is a powerful irritant,
particularly to the respiratory system; the activation of DMSO can
be violent and exothermic, and it must occur at low temperatures
layer chromatography and by H NMR. HReO
4
(5 mol %) proved
to be the best catalyst, affording 4-nitrobenzaldehyde in 99% yield
after 17 h (Table 1, entry 1). The oxo-molybdenum complexes
(
À60 °C). Several modifications on the Swern methodology have
MoO
(86–89%) (Table 1, entries 2 and 3). The oxo-vanadium complex
VO(acac) gave moderate yield (60%) of 4-nitrobenzaldehyde (Ta-
ble 1, entry 4), and finally WO Cl only produced low yield of the
product (Table 1, entry 5). In the reactions catalyzed by HReO
MoO Cl2, and MoO (acac) , 4-methylphenyl sulfide was isolated
in high yield (91–96%) (Table 1, entries 1–3).
The oxidation of 4-nitrobenzyl alcohol was also studied with
several sulfoxides as the oxidizing agent catalyzed by 5 mol % of
4
HReO in reflux of toluene under air atmosphere. Among all the
sulfoxides tested, the reactions with 4-methylphenyl sulfoxide, di-
phenyl sulfoxide, and 4-chlorophenyl sulfoxide produced the best
yields of 4-nitrobenzaldehyde (Table 2, entries 1–3). Good yields
of the sulfides were also isolated in the reactions with sulfoxides
like 4-methylphenyl sulfoxide, diphenyl sulfoxide, and 4-chloro-
phenyl sulfoxide (Table 2, entries 1–3). In the presence of DMSO,
4-nitrobenzyl alcohol was not oxidized (Table 2, entry 4).
2 2 2 2
Cl and MoO (acac) produced good yields of the aldehyde
been accomplished in order to overcome some of these disadvan-
tages.
Another traditional method for the oxidation of alcohols in-
volves the use of stoichiometric inorganic oxidants such as Cr(VI)
based reagents, which generate a large amount of heavy metal
3
–7
2
2
2
4
,
2
2
2
8
9,10
11–13
waste. Several oxo-vanadium,
oxo-molybdenum,
and
1
4
oxo-rhenium complexes have also proved to be efficient catalysts
for the oxidation of alcohols in the presence of molecular oxygen or
using hydroperoxide compounds as the oxidizing agent. Only a few
studies have also been reported for the oxidation of alcohols with
1
5–18
DMSO catalyzed by oxo-molybdenum or -rhenium complexes.
In continuation of our work about the use of oxo-complexes as
catalysts for oxidation/reduction reactions,1
9–27
in this communi-
⇑
Corresponding author. Tel.: +351 218419264; fax: +351 218464455.
E-mail address: anacristinafernandes@ist.utl.pt (A.C. Fernandes).
0
040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.08.145

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S. C. A. Sousa et al. / Tetrahedron Letters 53 (2012) 6205–6208
Table 1
Oxidation of 4-nitrobenzyl alcohol catalyzed by oxo-complexes using 4-methylphenyl sulfoxide as the oxidizing agent
a
Entry
Catalyst
HReO
Time (h)
Yield A/B (%)b
1
2
3
4
5
4
17
24
20
20
24
99/96
89/92
MoO
MoO
2
Cl
(acac)
2
2
2
86/91
d
d
VO(acac)
WO Cl
2
60/65 (26)c (31)
36/45 (52)c (40)
2
2
a
b
c
All reactions were carried out with 1.0 mmol of sulfoxide and 1.0 mmol of alcohol.
Isolated yield.
Alcohol recovered.
Sulfoxide recovered.
d
Table 2
Oxidation of 4-nitrobenzyl alcohol catalyzed by HReO
4
using different sulfoxides as the oxidizing agenta
Entry
1
Sulfoxide
Time (h)
17
Yield (%)b (A/B)
99/96
2
17
90/92
3
4
17
24
86/90
No reaction
a
All reactions were carried out with 1.0 mmol of sulfoxide and 1.0 mmol of alcohol.
Isolated yield.
b
To assess the scope and limitations of this novel methodology,
Compared to other methods reported in the literature, this proce-
dure does not require the use of DMSO as the oxidizing agent,
avoiding the production of the volatile and unpleasant dimethyl
sulfide. Another advantage of this method is that 4-methylphenyl
sulfide, obtained as by-product in high yields, can be used as a sub-
strate in other reactions or can be oxidized and reused in this
procedure.
In conclusion, we have developed a novel and an efficient method
for the selective oxidation of benzyl alcohols to the corresponding
aldehydes catalyzed by oxo-complexes using 4-methylphenyl sulf-
oxide as the oxidizing agent. Other advantages of this method in-
clude: 1) high isolated yields of aldehyde; 2) applicability to a
variety of alcohols; 3) use of commercial and easy-to-handle cata-
lyst; 4) use of a sulfoxide (other than DMSO) as the oxidizing agent;
5) high isolated yields of the sulfide that can be used in other reac-
tions or oxidized and reused in this method; and 6) simple experi-
mental operation.
we carried out the oxidation of several benzyl alcohols bearing
different functional groups using 4-methylphenyl sulfoxide as the
28
oxidizing agent catalyzed by 5 mol % of HReO
were carried out at refluxing toluene under air atmosphere
Table 3). As shown in Table 3, 4-nitrobenzyl, 4-bromobenzyl, 4-flu-
4
.
The reactions
(
orobenzyl, 4-iodobenzyl, benzyl, 4-chlorobenzyl alcohols, and
methyl 4-(hydroxymethyl)benzoate were oxidized in excellent
yields (70–99%), affording selectively the corresponding aldehydes
with no further oxidation to acids (Table 3, entries 1–7). Cinnamyl
alcohol was also chemoselectively oxidized to cinnamaldehyde in
moderate yield without affecting the double bond (Table 3, entry 8).
In contrast, the oxidation of the secondary diaromatic alcohols
4-nitrophenyl)(phenyl)methanol and bis(4-chlorophenyl)metha-
nol afforded the corresponding ketones in low to moderate yields
Table 3, entries 9 and 10). For most reactions, the sulfide was
(
(
isolated in high yields (80–99%).
The results obtained demonstrate that the catalytic system
Further mechanistic studies and new applications of this meth-
odology to the oxidation of other substrates are now under inves-
tigation in our group.
4
-methylphenyl sulfoxide/HReO
4
(5 mol %) is very efficient for
the oxidation of benzyl alcohols to the corresponding aldehydes.

S. C. A. Sousa et al. / Tetrahedron Letters 53 (2012) 6205–6208
6207
Table 3
Oxidation of alcohols catalyzed by HReO
4
using 4-methylphenyl sulfoxide as the oxidizing agenta
Entry
1
Alcohol
Carbonyl compound
Time (h)
17
Yield (%)b A/B
99/96
98/99
90/97
88/99
2
3
4
17
17
17
5
6
24
17
85/97
83/95
7
8
9
17
24
24
70/99
68/80 (15)c
55/85 (33)c
1
0
24
35/60 (49)c
a
b
c
All reactions were carried out with 1.0 mmol of sulfoxide and 1.0 mmol of alcohol.
Isolated yield.
Alcohol recovered.
3
4
.
.
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Acknowledgment
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793.
This research was supported by FCT through project PTDC/QUI-
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