The Dual Roles of Oxodiperoxovanadate Both as a Nucleophile and an Oxidant in the Green Oxidation of Benzyl Alcohols or Benzyl Halides to Aldehydes and Ketones

Article abstract of DOI:10.1002/anie.200351902

One catalyst, two roles: VO(O₂)₂^- reacts as a nucleophilic oxidant under acidic conditions towards benzyl alcohols. Altogether 15 alcohols have been oxidized, in the absence of organic solvent, in excellent yields. Benzyl halides are also oxidized by H₂O ₂ in water catalyzed by oxodiperoxovanadate and a phase transfer catalyst into aromatic aldehydes and ketones (see scheme). This reaction is the first green oxidation of benzyl halides.

Full text of DOI:10.1002/anie.200351902

Angewandte
Chemie
Green Chemistry
The Dual Roles of Oxodiperoxovanadate Both as
a Nucleophile and an Oxidant in the Green
Oxidation of Benzyl Alcohols or Benzyl Halides
to Aldehydes and Ketones
Chunbao Li,* Pengwu Zheng, Jie Li, Hang Zhang,
Yi Cui, Qiyun Shao, Xiujie Ji, Jian Zhang,
Pengying Zhao, and Yanli Xu
Sulfoxides and tertiary amine oxides have similar structures in
that the oxygen atom is partially negatively charged. Both can
react as a nucleophilic oxidant toward halides, which are
converted into aldehydes or ketones. Recently, we found that
dimethylsulfoxide (DMSO)is capable of oxidizing benzyl
alcohols to benzaldehydes in high yields when catalyzed by
acid. DMSO is believed to function as a nucleophilic
oxidant.[1] Traditionally, Mn+4, Mn+6, Cr+6, and Fe+6 reagents
are the commonly used oxidants for alcohols.[2,3] These
reagents must be used in stoichiometric amounts and yield
side products that require costly disposal. In these oxidations,
the metal oxides or metalates react as an electrophile toward
the alcohols in most of the cases.[3] Similarly, the peroxides of
NaMoO4 and Na2WO4, which are excellent catalysts in the
oxidation of alcohol by H2O2, were proposed to act as an
electrophile towards alcohols.[4]
Vanadium peroxide was reported to be involved in a
number of reactions[5] such as the oxidation of ethanol to
[*] Dr. C. Li, P. Zheng, J. Li, H. Zhang, Y. Cui, Q. Shao, X. Ji, J. Zhang,
P. Zhao, Y. Xu
Department of Chemistry
School of Sciences
Tianjin University
Tianjin 300072 (China)
Fax : (+86)22-2740-3475
E-mail: lichunbaosyn@sohu.com
Angew. Chem. Int. Ed. 2003, 42, 5063 –5066
DOI: 10.1002/anie.200351902
ꢀ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5063

Communications
acetaldehyde, and 2-propanol to acetone with H2O2 and
mide; 0.05 equiv)as the catalysts. The reaction did not take
place at room temperature or at reflux. On acidification to
pH 4 with HBr, HCl, H2SO4, or H3PO4, the oxidation of
benzyl alcohol to benzaldehyde readily took place at 608C.
Above pH 5 there was almost no oxidation. A plot of TOF
against pH indicates that the reaction rate increases with the
acidity of the reaction mixture (Figure 1). The reaction
mixture was initially red and became yellow as the reaction
proceeded. In the work up, the vanadium reagents were
removed by simply washing with aqueous NaOH. A total of
15 liquid alcohols were oxidized by dilute aqueous H2O2 (1.2
to 2.8 equiv), with V2O5 (0.05 equiv), and BTEAB
(0.05 equiv)catalysts at 60 8C at pH 2 without the use of any
organic solvents. Table 1 presents the reaction times and
VO(OiPr)3,[6] the oxidation of alcohols to aldehydes or ketones
by using H2O2 and vanadium silicate xerogel,[7] and the aerobic
oxidation of propargylic alcohols to ketones catalyzed by
VO(acac)2 (Hacac =acetylacetone).[8] The discovery of vana-
ꢀ
dium bromoperoxidase (V BrPO)in marine organisms has
stimulated more active research on vanadium peroxide
chemistry.[5,8–12] Although it is well documented that under
acidic conditions V2O5 can be oxidized by H2O2 into vanadium
peroxide,[5] there is no report of the oxidation of alcohols with
H2O2 catalyzed by V2O5. We envisioned that VO(O2)2ꢀ could
behave in a similar way to DMSO as a nucleophilic oxidant
toward alcohols (Scheme 1). But this type of reaction has never
been reported in the literature for metalates.
Scheme 1. Proposed mechanism for the oxidation of alcohols with
H2O2 catalyzed by V2O5 and PTC.
Figure 1. Plot of TOF (hꢀ1) against pH in the oxidation of benzyl alco-
hol to benzaldehyde using H2O2 catalyzed by V2O5 and PTC.
In addition, the oxidation of benzyl halides to aldehydes is
a significant reaction because aromatic aldehydes are used
widely. For example, benzaldehyde alone produced in the
United States, Western Europe, and Japan in 1983 amounted
to 19500 tons.[13] There are two major methods of production
of aromatic aldehydes in use. The first method is the
hydrolysis of benzal chloride. The problem is that benzal
chloride is often contaminated by benzyl chloride and
trichloromethyl benzene. In addition, benzal chloride is
toxic and carcinogenic.[13] The second method is the oxidation
of the methyl group on the aromatic ring, which involves the
use of complicated equipment and catalysts. The yield for
benzaldehyde is only 40–60% and side products such as
maleic anhydride, citraconic anhydride, phthalic anhydride,
anthraquinone, CO and CO2 are produced.[13]
Several oxidations of organic halides to carbonyl com-
pounds are known. These include the Hass–Bender reac-
tion,[14] the Sommelet reaction,[15] the Krohnke reaction,[16] the
Kornblum reaction,[17] oxidations by using amine N-oxide,[18]
the Masaki photooxidation,[19] and oxidations by using
NaIO4.[20] Stoichimetric amount of oxidants have to be used
in most of these oxidations. Although the Masaki photo-
oxidation offers the advantage that oxygen is used as the
oxidant, volatile organic solvents such as acetone or CH2Cl2
are also used in the oxidation.
Table 1: BTEAB and V2O5 catalyzed oxidation of benzyl alcohols to
aldehydes or ketones by H2O2.
Entry
Alcohol
Time [h]
Yield [%][a]
1
2
3
4
5
6
7
8
PhCH2OH
PhCH(OH)CH3
6.0
2.0
1.5
8.0
7.0
7.5
10.0
7.0
34.0
8.5
2.5
2.4
2.2
30.0
36.0
40
84
81
81
83
84
82
83
90
81
87
88
85
87
84
88
0
PhCH(OH)(CH2)3CH3
p-MeOC6H4CH2OH
p-ClC6H4CH2OH
o-ClC6H4CH2OH
p-MeC6H4CH2OH
o-BuOC6H4CH2OH
10
11
12
13
14
15
16
17
2,5-Br2C6H3CH2OH
Ph2CHOH
p-ClC6H4CH(OH)(CH2)3Me
p-MeC6H4CH(OH)(CH2)3Me
cyclohexanol
menthol
Menthol[b]
BnCl[c]
6
85
[a] A mixture of benzyl alcohol (0.5 g), H2O (10 mL), V2O5 (0.05 equiv),
H2O2 (30%, 1.2–2.8 equiv), and BTEAB (0.05 equiv) adjusted to pH 4
with H2SO4 and was heated to reflux for the indicated time. After the
reaction mixture was cooled to room temperature, it was added to
aqueous NaOH (20%, 5 mL) and extracted with ether three times. The
organiclayer was combined and dried and the solvents were removed by
evaporation to give the desired product, which was analyzed by IR and
1HNMR. [b] Aliquat 336 (0.05 equiv) used instead of BTEAB. [c] Benzal-
dehyde as product.
To solve these existing problems, we started our research
by treating benzyl alcohol with dilute H2O2, V2O5
(0.05 equiv), and BTEAB (benzyltriethylammonium bro-
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Chemie
yields for these reactions. All the alcohols were oxidized into
the corresponding aldehydes or ketones with excellent yields.
The benzyl alcohols are oxidized much faster than aliphatic
alcohols (entries 14 and 15)and secondary alcohols are
oxidized faster than primary alcohols (entries 1, 4–8 versus
entries 2 and 3). The presence of the electron-withdrawing
group on the aromatic ring (entry 9)leads to a lower rate of
oxidation of the m-nitrobenzyl alcohol.
When the oxidation was performed under a nitrogen
atmosphere, a similar reaction rate was observed. The
reaction did not proceed under an oxygen atmosphere when
hydrogen peroxide was not present. These results indicate
that oxygen is not the oxidant in these reactions, although this
was proposed by Conte et al. in the oxidation of alcohols by
VO(OiPr)3 and oxygen.[21] To determine the effect of
bromide, we used n-butoxybenzylalcohol as the substrate
and replaced BTEAB with Aliquat 336 (0.05 equiv)in both
the absence and presence of potassium bromide (0.05 equiv).
Both reactions proceeded at almost the same rate (8.5 h), but
without the catalytic amount of V2O5, the oxidation was very
sluggish. This suggests that the primary function of BTEAB is
a phase transfer catalyst (PTC)and the oxidation of alcohol
by bromine can be ignored.
As indicated in Table 1, the oxidation rate of m-nitro-
benzyl alcohol is only one fifth that of benzyl alcohol (entry 9
versus entry 1). This suggests that this oxidation does not
occur by a radical pathway but most probably by a nucleo-
philic oxidation pathway (Scheme 1). Under acidic condi-
tions, benzyl alcohol is protonated and produces a benzyl
cation, which is attacked by VO(O2)2ꢀ to form intermediate C.
Losing a proton, intermediate C decomposes into benzalde-
hyde. The rate-determining step is the formation of benzyl
cation. This is supported by the fact that the secondary benzyl
alcohols are oxidized three to four times faster than the
primary benzylalcohols and 16 times faster than the aliphatic
alcohols.
expensive one. We used H2O2 as the oxidant because it has
high oxygen content, is inexpensive and stable. V2O5 is also
inexpensive and stable. Unfortunately, this oxidation is
limited to benzyl alcohol because of the unique mechanism
related to oxodiperoxovanadate.
To broaden the potential application of oxodiperoxova-
nadate, we oxidized both primary and secondary benzyl
chlorides and bromides to aldehydes and ketones in boiling
water using H2O2 (1.5 equiv)catalyzed by V 2O5 (0.05 or
0.1 equiv)and Aliquat 336 (0.05 equiv.) The 22 organic
halides (Table 2)were all oxidized in good yields to the
corresponding aldehydes or ketones. The oxidation is com-
patible with amides (entry 9), esters (entries 8 and 11), ethers
(entries 5, 6, 7 and 13), aryl halides (entries 2, 3, 10, 18 and 11)
and phenolic (entries 4 and 12)groups. Primary halide are
oxidized faster than secondary halides, which suggests that the
ꢀ
OV(O2)2 anion is a bulky nucleophile and is sensitive to
steric hindrance. The reaction is faster with benzyl chlorides
than with benzyl bromides. A possible reason is that -OV(O2)2
is such a good leaving group that it is more easily substituted
by the better nucleophile, bromide ion, than by the chloride
ion. The following equilibrium exists [Eq. (1)].
ArCH2Br þ VOðO2Þꢀ2 Ð ArCH2OVðO2Þ2 þ Brꢀ
ð1Þ
A comparative experiment was carried out to verify this.
When benzyl chloride was oxidized by H2O2 (1.5 equiv)
catalyzed by V2O5 (0.05 equiv)and Aliquat 336 (0.05 equiv)
Table 2: Oxidation of benzyl halides to aldehydes and ketones by H2O2
catalyzed by V2O5 and Aliquat 336.[a]
Entry Benzyl Halide
Time [h]
Yield [%][b]
1
2
PhCH2Cl
p-ClC6H4CH2Cl
6.0(3.5) 70(90)
6.0 (3.5) 73(90)
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
o-ClC6H4CH2Cl
7.0
5.0
6.0
8.0
11.0
8.0
6.0
10.0
8.0
75
81
87
82
80
73
83
82
76
80
82
77
72
81
78
81
84
85
75
75
o-HOC6H4CH2Cl
o-BnOC6H4CH2Cl
o-nBuOC6H4CH2Cl
o-iBuOC6H4CH2Cl
o-BzOC6H4CH2Cl
p-AcNHC6H4CH2Cl
2,5-Br2C6H3CH2Cl
p-BzOC6H4CH2Cl
1-chloromethyl-2-hydroxynaphthalene
1-benzyloxy-2-chloromethylnaphthalene 12.0
PhCHClMe
PhCHClEt
PhCHClBu
p-MeC6H4CHClBu
p-ClC6H4CHClBu
PhCH2Br[c]
p-BrC6H4CH2Cl
1-bromomethylnaphthalene
PhCHBrMe
To further prove the mechanism, we subjected benzyl
chloride to the same oxidation conditions. Benzaldehyde was
formed in 85% yield in 6 h. Therefore it is easy to understand
why the oxidations of menthol and cyclohexanol occur at
much lower reaction rates. When menthol was treated with
H2O2 (2.5 equiv)catalyzed by V 2O5 at pH 2 in the presence of
Aliquat 336 (0.05 equiv)instead of BTEAB, no reaction took
place after 40 h (entry 16). This result suggests that the low
concentration of bromine is the oxidant here (entry 15)and
13.0
10.0
10.0
12.0
10.0
12.0
14.0
15.0
20.0
24.0
ꢀ
VO(O2)2 is not a good enough nucleophile to substitue
efficiently the protonated hydroxyl group of aliphatic alco-
ꢀ
hols. Our attempt at trapping VO(O2)2 with TrCl or TsCl
failed, which suggests that -OV(O2)2 is a very good leaving
group and intermediate C is extremely unstable.
Therefore, we have for the first time demonstrated the
ꢀ
dual roles of VO(O2)2 both as a nucleophile and oxidant
[a] Typical procedure: A mixture of p-chlorobenzyl halide (10 g), H2O
(10 mL), H2O2 (30%, 1.5 equiv), V2O5 (0.005 equiv) and Aliquat 336
(0.05 equiv) was refluxed for 6 h. After cooling to room temperature, the
oil layer was separated and distillated to give pure p-chlorobenzaldehyde
in 73% yield. The aqueous phase was reused for the subsequent
oxidation. For the eight subsequent oxidations, the reaction time was
3.5 h and the yield was more than 90%. [b] The conversion for chlorides
was quantitative. [c] 0.1 equivalents of V2O5 were used for bromide.
toward alcohols. This reaction mechanism is rare among
metal oxides and metalate oxidants. We have established a
new green oxidation procedure of alcohols with H2O2
catalyzed by V2O5 and BTEAB. Although several green
oxidation procedures of alcohols are known,[22] in most cases
expensive metals such as Ru,[23] Pd,[24] Pt,[25] Ir[26] and Rh[27] are
used as catalysts. This makes the oxidation process an
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[16] T. Nishimura, T. Onoue, K. Ohe, S. Uemura, J. Org. Chem. 1999,
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and KBr (1.0 equiv), the reaction took 2 h longer than in the
absence of KBr (entry 1). In addition, this result agrees well
ꢀ
with the fact that the OV(O2)2 anion could not be trapped
with TrCl (see above). We also found that OV(O2)2ꢀ ion is an
excellent catalyst. The separated aqueous phase containing
ꢀ
OV(O2)2 ions and PTC was used in the subsequent eight
oxidation runs. In the first run of the oxidation of benzyl
chloride and p-chlorobenzyl chloride, the yield was 70% and
73% respectively, the reaction time was 6 h. In the subse-
quent eight runs the yield was 90% and the reaction time was
shortened to 3.5 h. The reaction is self-accelerated by the
accumulated HCl. In the catalytic oxidation of p-chlorobenzyl
chloride, the substrate/catalyst ratio reached 1000:5 and the
reaction rates and the yields remained unchanged.
In our oxidation, only water was used to dilute the H2O2,
no organic solvents were used in the whole process. This
represents the first green oxidation of benzyl halides, which is
operationally simple and produces high yields and is well
suited for a variety of functionalized benzyl halides. Our new
green oxidation reaction provides a better solution for the
existing problems in the oxidation of benzyl halides. The
conversion of organic chlorides to aromatic aldehydes is
quantitative. The yields are more than 90%. The whole
process does not need any organic solvents. The two waste
products are water and HCl. The latter provides acidic
conditions to accelerate the reaction. The catalysts (V2O5 and
Aliquat 336)are inexpensive, stable and efficient (S/C 1000:5)
and can be reused without losing its efficiency.
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[27] J. Martin, C. Martin, M. Faraj, J.-M. Bregeault, Nouv. J. Chim.
1984, 8, 141.
Received: May 14, 2003
Revised: August 18, 2003 [Z51902]
Keywords: alcohols · green chemistry · oxidation · vanadium
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