A green process for the oxidative lactonization of 1,2-benzenedimethanol by tungstic acid with aqueous H2O2

Article abstract of DOI:10.1039/b921334a

A new economic and green route to synthesize phthalide from 1,2-benzenedimethanol using aqueous hydrogen peroxide as the oxidant and tungstic acid as the catalyst under organic solvent-free conditions is presented. This process proceeds with advantages from the viewpoint of green chemistry, in which the only by-product of H₂O₂ is water and the catalyst can also be easily recovered. The desired product with high purity and good yield can be conveniently obtained when cooled after reaction.

Full text of DOI:10.1039/b921334a

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www.rsc.org/greenchem | Green Chemistry
A green process for the oxidative lactonization of 1,2-benzenedimethanol by
tungstic acid with aqueous H O †
2
2
Quan-Jing Zhu, Wei-Lin Dai* and Kang-Nian Fan
Received 15th October 2009, Accepted 16th November 2009
First published as an Advance Article on the web 7th December 2009
DOI: 10.1039/b921334a
A new economic and green route to synthesize phthalide
from 1,2-benzenedimethanol using aqueous hydrogen per-
oxide as the oxidant and tungstic acid as the catalyst under
organic solvent-free conditions is presented. This process
proceeds with advantages from the viewpoint of green
its derivatives are commonly used in the manufacturing of dyes,
11
pharmaceuticals, bactericides and other useful products. The
oxidation of 1,2-benzenedimethanol with aqueous H is an
2
O
2
effective green process for the synthesis of phthalide, owing to
the avoidance of waste or pollutant.
Phthalide is traditionally synthesized by reaction of phthalic
anhydride, zinc and hydrochloric acid; reaction of phthal-
imide and sodium hydroxide; or hydrogenation of phthalic
chemistry, in which the only by-product of H
2
2
O is water
and the catalyst can also be easily recovered. The desired
product with high purity and good yield can be conveniently
obtained when cooled after reaction.
12
anhydride. During these processes, serious environmental
pollution is generated, a low yield of phthalide is obtained, or a
high reaction temperature is required, which consumes a large
amount of energy.
At present, the development of environmentally friendly tech-
niques in the field of oxidation of organic compounds has
attracted much attention because the reagents used in stoichio-
metric amounts in these reactions are sometimes wasteful and
toxic. Therefore, there is an urgent need to replace the classic
In the present work, the optimal reaction conditions are
investigated in detail by using WO ·H O as the catalyst and tert-
3
2
butanol as the solvent, bearing in mind that the tert-butanol–
oxidants with “clean” oxygen donors, such as H
that the oxidation of organic substrates using hydrogen peroxide
as an oxidant has long been studied. Many useful reactions
2
O
2
. It is known
H O system is stable and has been used in a large number
of oxidation reactions. In addition, analysis by GC is very
2
2
13
convenient in the tert-butanol–H O system. Then, under the
2
2
carried out with H
2
O
2
have been developed, such as the oxidation
optimized conditions, a green and novel approach to produce
phthalide from 1,2-benzenedimethanol by catalytic oxidation
with aqueous H O without using organic solvents is presented
1
of sulfides to sulfoxides and sulfones, epoxidation of olefins and
2
allylic alcohols and the oxidative cleavage of carbon–carbon
2
2
3
4
double bonds to aldehydes and acids. To date, the oxidation of
diols to lactones with H has been rarely reported.
Lactones and their derivatives are ubiquitous in nature.
Many substances containing the lactone ring show interesting
biological activity. Lactones can also be used in the production
because the reaction conditions are similar. In particular,
aqueous hydrogen peroxide as an oxidant is environmentally
clean, easy to handle and tungstic acid is an inexpensive catalyst.
In this study, the catalyst can be easily removed by simple
filtration after reaction because little H O remains after reaction
2
O
2
5
6
2
2
7
◦
of a variety of polymers. Although oxidation of alcohols has
and it can be decomposed when heated at 90 C, which leads
been widely used for the synthesis of lots of chemicals, the
oxidation of diols to lactones usually requires fierce reaction
conditions and specific oxidants. The reaction can be carried
out under mild conditions in the presence of organic cooxidants
to the deposit of WO ·H O. The desired product phthalide can
3
2
be easily obtained through cooling the reaction system because
phthalide undergoes thermally reversible changes between the
water-soluble and water-insoluble states from hot water to warm
water at room temperature.
8
which are not green oxidants, such as a,b-unsaturated ketones,
9
PhBr, N-methylmorpholine N-oxide, or acetone. Mitsudome
The activity test was performed at a set temperature for a
given time with magnetic stirring in a closed 25 ml regular
glass reactor using 50% aqueous H O as the oxygen-donor and
et al. recently obtained a high yield of lactones (99%) from
diols using molecular oxygen as the oxidant and supported
2
2
10
gold nanoparticles as the catalyst under mild conditions.
t-BuOH as the solvent. In a typical experiment, 0.0135 g of
WO ·H O (0.054 mmol) and 0.67 ml of 50 wt% aqueous H O
However, the catalyst is expensive and cannot be easily syn-
thesized. Among the diol oxidations to lactones, the oxidative
lactonization of 1,2-benzenedimethanol to phthalide can be
taken into account as a probe reaction, since phthalide and
3
2
2
2
(11.1 mmol) were introduced into the regular glass reactor at
◦
40 C with vigorous stirring. Then, the reaction was started
after the addition of 10 ml of t-BuOH and 0.690 g of 1,2-
benzenedimethanol (5 mmol) into the mixture, which was left
for 24 h or more. The conversion of H
2
2
O was measured
Department of Chemistry & Shanghai Key Laboratory of Molecular
Catalysis and Innovative Material, Fudan University, Shanghai, 200433,
P. R. China. E-mail: wldai@fudan.edu.cn; Fax: (+86-21) 55665572;
Tel: (+86-21) 55664678
by a standard iodimetric titration method. The quantitative
analysis of the reaction products was performed by using a
GC method and the identification of different products in the
reaction mixture was determined by means of GC-MS on HP
†
Electronic supplementary information (ESI) available: Experimental
section, H-MNR and XRD data. See DOI: 10.1039/b921334a
1
1
6890GC/5973 MS, and H NMR on DMX 500.
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According to the GC-MS analysis, the products of the
catalytic oxidation of 1,2-benzenedimethanol, as shown in
Scheme 1, comprise the main product phthalide and small
amounts of by-product involving phthalaldehyde, phthalic
acid and 1,3-dihydroisobenzofuran. Phthalaldehyde could be
oxidized to phthalic acid. The catalytic performance and the
optimization of the reaction conditions are based on the yield
of phthalide.
Table 1 Catalytic performance of the oxidation of 1,2-benzene-
a
dimethanol with various molar ratios of H
2 2
O to substrate
Conversion (%)
H
2
O
2
:substrate
H
2
O
2
Yield (%)
1.5 : 1
79
94
100
100
100
98
98
97
86
87
57
85
90
84
86
2
2
3
4
: 1
.2 : 1
: 1
: 1
a
◦
Reaction conditions: reaction temperature 80 C, 1,2-benzene-
dimethanol 5 mmol, WO
t-BuOH 10 ml.
3
·H
2
O catalyst 0.054 mmol, reaction time 24 h,
2 2
Scheme 1 The oxidation products of 1,2-benzenedimethanol by H O .
Table 2 Catalytic performance of the oxidation of 1,2-benzene-
To elucidate the reaction process, the course of the conversion
of 1,2-benzenedimethanol over time is tested, as shown in Fig. 1.
It is suggested that the reaction proceeds rapidly at the first
a
dimethanol over various temperatures
Conversion (%)
6
h and then the reaction rate decreases slowly, which can be
◦
Entry
T/ C
H
2
O
2
Yield (%)
explained by the fact that the concentration of H and 1,2-
2
O
2
benzenedimethanol decreases over time. Complete consumption
of 1,2-benzenedimethanol is achieved when the reaction time
reaches 12 h, whereas the yield of phthalide is only 72%. It
is interesting to find that the yield of phthalide ascends with
the prolonging of the reaction time. This phenomenon may be
1
2
3
4
50
60
70
80
67
77
98
100
53
66
88
97
26
46
74
90
a
Reaction conditions: 1,2-benzenedimethanol
5
mmol,
2 2
H O
14
due to the mechanism of the oxidative lactonization of diols.
11.1 mmol, WO
0 ml.
3
·H O catalyst 0.054 mmol, reaction time 24 h, t-BuOH
2
1
The formation of phthalide proceeds via two steps: the initial
chemoselective oxidation to 2-(hydroxymethyl)benzaldehyde,
which is in equilibrium with 1,3-dihydroisobenzofuran-1-ol,
and then the oxidation of 1,3-dihydroisobenzofuran-1-ol to
phthalide. The phthalide would not be hydrolyzed upon con-
tinuing to elongate the reaction time under the present reaction
conditions.
when the ratio of H O to 1,2-benzenedimethanol reaches 2.2 : 1.
2
2
Although 100% 1,2-benzenedimethanol conversion could still
be retained with further increasing the molar ratio, the yield
of phthalide would decrease because of the over-oxidation,
which may be a result of the further oxidation of the phthalide
to phthalide acid. Considering both catalytic performance
and H
2
O
2
utility, the 2.2 : 1 molar ratio of the H
2
2
O to 1,2-
benzenedimethanol is needed and is used in the following
investigations.
It is known that the reaction temperature is essential to every
reaction. As shown in Table 2, a higher temperature benefits
the conversion of 1,2-benzenedimethanol and the formation of
phthalide. Complete consumption cannot be achieved when
◦
◦
the temperature is lower than 80 C. Therefore, 80 C was
chosen as the optimal reaction temperature because H
decompose at temperatures higher than 80 C.
2
2
O would
◦
Independent experiments were carried out to obtain an insight
into the effect of the amounts of catalysts on this reaction (see
Table 3). As can be seen, there is a strong dependence of the
conversion of 1,2-benzenedimethanol and the yield of phthalide
on the dosage of the catalysts. The importance of the use of
WO ·H O was evident because the reactions gave much lower
Fig. 1 Conversion of 1,2-benzenedimethanol and H
of phthalide. (Reaction conditions: reaction temperature 80 C, 1,2-
2
O
2
and the yield
◦
benzenedimethanol 5 mmol, H
.054 mmol.)
2
O
2
11.1 mmol, WO
3
·H
2
O catalyst
0
3
2
conversion of 1,2-benzenedimethanol and H
2
2
O , and lower yield
The reaction rate and the yield of products are dependant on
the amount of H . Table 1 shows the catalytic performance
of the oxidation of 1,2-benzenedimethanol with various molar
ratios of H to 1,2-benzenedimethanol. As can be seen, the
conversion of 1,2-benzenedimethanol ascends with an increase
in the molar ratio of H to 1,2-benzenedimethanol when
of phthalide without any catalysts (Entry 1). In addition, it can
be seen that the conversion of 1,2-benzenedimethanol increases
with increasing catalyst dosage, the amounts of which range
from 0 to 0.0135 g (0.054 mmol). The amount of catalyst
influences the reaction rate and selectivity to the phthalide.
However, when the amount is higher than 0.0135 g, the
conversion of 1,2-benzenedimethanol and the yield of phthalide
descends with an increase in the amount of catalyst. This is likely
2
O
2
2
O
2
2
O
2
the ratio is lower than 2.2 : 1. Complete consumption of 1,2-
benzenedimethanol and a 90% yield of phthalide can be achieved
2
06 | Green Chem., 2010, 12, 205–208
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a
a
Table 3 The effect of the amount of catalyst on the reaction
Table 5 The effect of different solvents on the reaction
Conversion (%)
Conversion (%)
Amount of
Entry catalyst/g Catalyst:substrate
Solvents
H
2
O
2
Yield (%)
H
2
O
2
Yield (%)
n-Butanol
86
27
100
100
93
99
100
98
96
100
26
7
90
89
18
1
2
3
4
5
0
0
31
94
100
96
64
98
97
98
98
7
2
-Propanol
0.0051
0.0135
0.0249
0.1001
0.004
0.011
0.020
0.080
65
90
71
46
tert-Butanol
Water
Acetonitrile
93
a
◦
a
◦
Reaction conditions: reaction temperature 80 C, reaction time 24 h,
Reaction conditions: reaction temperature 80 C, 1,2-benzene-
1
2 2
,2-benzenedimethanol 5 mmol, H O 11.1 mmol, solvent 10 ml.
2 2
dimethanol 5 mmol, H O 11.1 mmol, reaction time 24 h, t-BuOH 10 ml.
◦
9
0 C after the reaction. The product was separated out when
the filtrate was cooled to room temperature and a 77.4% yield of
the separated phthalide was obtained. The melting point of the
Table 4 The effect of volumes of t-BuOH on the oxidation of 1,2-
a
benzenedimethanol
◦
Conversion (%)
Volumes of
powder obtained by this route was 70.0 to 73.8 C (Sinopharm
◦
Chemical Reagent Co., Ltd, 71.0 to 75.0 C). The GC purity of
the as-prepared phthalide was higher than 99.5%, and it can be
used directly in many fields. In addition, H NMR spectroscopy
t-BuOH/ml
H
2
O
2
Yield (%)
1
2
5
1
1
2
100
100
100
100
99
98
99
97
96
90
87
88
90
77
72
and the XRD pattern of the product confirmed that the structure
of the powder was that of phthalide (see Figure S1 and Figure
S2, ESI†).
In summary, a new, economic and efficient route for
the production of phthalide by catalytic oxidation of 1,2-
O has been developed
using tungstic acid as a catalyst under organic solvent-free
conditions. This process can be easily commercialized based on
0
5
0
a
◦
Reaction conditions: reaction temperature 80 C, reaction time 24 h,
benzenedimethanol with aqueous H
2
2
1
0
,2-benzenedimethanol 5 mmol, H
.054 mmol.
2
O
2
11.1 mmol, WO
3
·H
2
O catalyst
the following considerations. Firstly, the molar ratio of H
to 1,2-benzenedimethanol is only 2.2 : 1, which is only 10%
molar excess, thus the utilization efficiency of H is very high
and this process is very economical. Secondly, the tungstic acid
catalyst can be easily filtrated after reaction and the phthalide
product can be removed from the reaction system after cooling
the reaction mixture to room temperature. The used tungstic
acid catalyst can be reused more than 6 times, thus leading to its
2
O
2
related to the consumption of H
which decreases the utility of H
The reaction results as a function of the volumes of t-BuOH
were also studied (see Table 4). It is obvious that there is an
optimum volume of tert-butanol at which a maximum yield of
phthalide is formed. The yield of phthalide increases from 72 to
2
O
2
by the excess WO
3
·H
2
O,
2
O
2
.
O
2
2
9
0% with a decrease in the volume of t-BuOH from 20 to 10 ml.
Such a phenomenon is not surprising when considering the fact
that the concentration of active oxidizing species that depends
great economical efficiency. Thirdly, the concentration of H
2
O
2
is low due to the presence of water, therefore, it is safe to handle
in industry. Finally, there is no need to use organic solvent in this
transformation, so it is environmentally benign and low-cost. A
on the concentration of H
2
2
O is required for the formation of
phthalide. When the dosage of t-BuOH is lower than 10 ml, there
is a negligible decrease in the yield of phthalide.
further investigation of the present H
2
2
O –tungstic acid catalytic
Solvent also has a crucial impact on the production of
fine chemicals over homogeneous catalysts, and thus it was
decided to study the solvent effect. Table 5 indicates that the
maximum yield of phthalide is formed when the solvent is tert-
butanol or water. Lower conversion of 1,2-benzenedimethanol
was obtained in n-butanol and 2-propanol, as well as a lower
yield of phthalide. It is interesting to find that the selectivity
of phthalide in acetonitrile as a solvent was much lower than
that in tert-butanol and water, although the conversion of 1,2-
benzenedimethanol was a little lower than that in tert-butanol
and water. The mechanism of the catalytic oxidation in these
solvents is still under investigation.
system in many other significant transformations from a,w-diols
to lactones is currently under way.
Acknowledgements
Financially supported by the Major State Basic Resource
Development Program (Grant No.2003CB615807), NSFC
(Project 20973042, 20573024), and the Science and Technology
Commission of Shanghai Municipality (08DZ2270500).
Notes and references
Since the yield of phthalide in water is similar to that in
t-BuOH (see Table 5), a novel process to separate phthalide
from the reaction mixture was explored in water. As we know,
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