292 New J. Chem., 2011, 35, 292–298 This journal is c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2011
Facile and efficient hydrolysis of organic halides, epoxides, and esters
with water catalyzed by ferric sulfate in a PEG1000-DAIL[BF4]/toluene
temperature-dependent biphasic system
Yu Lin Hu, Hui Jiang, Jie Zhu and Ming Lu*
Received (in Gainesville, FL, USA) 14th June 2010, Accepted 2nd November 2010
DOI: 10.1039/c0nj00454e
An efficient and environmentally friendly procedure for the hydrolysis
of organic halides, epoxides, and esters with water catalyzed by ferric
sulfate in a PEG1000-DAIL[BF4]/toluene temperature-dependent
biphasic system has been developed. The product can be easily
isolated by a simple decantation, and the catalytic system can be
recycled and reused without loss of catalytic activity.
Hydrolysis of organic halides, epoxides, and esters is one of the
most fundamental transformations both in laboratory
synthesis and industrial production.1,2 The most commonly
employed procedures for hydrolysis can be performed in acidic
or alkaline media, with the use of enzymes or with the aid of
metal ions.3–6 However, these described conditions are in most
cases rather harsh. Moreover, long reaction times and high
reaction temperatures are often required. To speed up the
hydrolysis reactions, the use of micellar catalysis,7 phase
transfer catalysis,8 ultrasonic irradiation,9 microwaves,10 and
others11 have been applied to accomplish this transformation
with different degrees of success. Transition metal-catalyzed
hydrolysis of organic halides, epoxides, and esters has been
developed with some innovative progress in recent years,12
whilst most of the reactions still require the use of expensive
reagents, long reaction times of more than 24 hours, elevated
reaction temperatures, and difficulties in recycling of the
catalyst. Consequently, the search for new and environmen-
tally benign catalytic hydrolysis systems that address these
drawbacks remains to be of value and interest.
Room temperature ionic liquids, a kind of environmental
friendly solvents and catalysts, because of their adjustable
physical and chemical properties, got broad attention of
scholars from various fields such as synthesis, catalysis, separa-
tion, and electrochemistry.13,14 Some novel ionic liquid–organ-
ic solvent mixtures as temperature dependent biphasic systems
have been reported.15 We as well as Luo and co-workers have
described a new PEG1000-based dicationic ionic liquid
(PEG1000-DAIL) exhibiting temperature-dependent phase
behavior with toluene and applied it in one-pot synthesis
of benzopyrans successfully.16 Utilization of such biphasic
systems can improve product isolation as well as catalyst
recovery. We herein report an efficient and environmentally
friendly protocol for the hydrolysis of organic halides,
epoxides, and esters with water catalyzed by ferric sulfate
(Fe2(SO4)3) in the PEG1000-based dicationic ionic liquid
(PEG1000-DAIL[BF4])/toluene temperature-dependent bipha-
sic system (Scheme 1).
It was determined during a preliminary survey of the
reaction conditions that we should use 1-(chloromethyl)-4-
methoxybenzene as the model substrate in the presence of
copper(II) sulfate (Table 1). As H2O was used as the
nucleophile, initial reaction screening led to disappointing
results in the absence of an ionic liquid, the reaction
proceeded very slowly, and the yield was only 29% after 7 h
(Table 1, entry 1). The results mean that copper(II) sulfate
alone does not work as an effective catalyst in the hydrolysis
reaction. The effects of different ionic liquids such as PEG600-
DAIL, PEG800-DAIL, PEG1000-DAIL, PEG1000-DAIL[BF4],
PEG1000-DAIL[PF6], and PEG1000-DAIL[OTf] were then
screened in this hydrolysis (Table 1, entries 2–7), and it was
observed that PEG1000-DAIL[BF4] demonstrated the best
performance. The different catalytic abilities of the ILs
(PEG600-DAIL, PEG800-DAIL, and PEG1000-DAIL) should
be attributed to their different abilities of forming
homogeneous catalytic media by exhibiting a temperature-
dependent phase behavior with toluene. This two phase
medium is changed to a homogeneous one at elevated
temperatures. Under the same conditions, the IL which
forms a homogeneous catalytic medium in combination with
toluene more easily will lead to a larger increase in the effective
reactant concentration, which increases the encounter
probability between the reactive species. Thus, the observed
rate and yield of the reaction is PEG1000-DAIL > PEG800-
DAIL > PEG600-DAIL. For a blank test (Table 1, entry 8), a
lower yield of the product was obtained while the same
reaction condition was carried out in the absence of
copper(II) sulfate. The result indicates that this cocatalyst
must play an important role in accelerating the rate of the
reaction. Finally, we also tried to use other types of cocatalysts
in the reaction (Table 1, entries 9–16), the results showed that
FeSO4, Fe2(SO4)3, and Cu(OAc)2 were the same effective
cocatalysts as CuSO4. Among them, Fe2(SO4)3 was found to
be the most effective cocatalyst in terms of yield and reaction
rate. Therefore, the optimal reaction conditions were observed
in Table 1, entry 10.
In addition, the catalytic system could be typically recovered
and reused for subsequent reactions with no appreciable
decrease in yields and reaction rates (Fig. 1). The recycling
process involved the removal of the top oil layer (toluene
containing product) by decantation. The bottom aqueous
layer (catalytic system) was concentrated under vacuum to
College of Chemical Engineering, Nanjing University of Science and
Technology, Nanjing 210094, PR China.
E-mail: luming1963@163.com; Fax: +86 025-84315030;
Tel: +86 025-84315030
LETTER www.rsc.org/njc | New Journal of Chemistry
D
ow
nl
oa
de
d
by
U
ni
ve
rs
ity
o
f S
ci
en
ce
a
nd
T
ec
hn
ol
og
y
of
C
hi
na
o
n
12
A
pr
il
20
12
Pu
bl
ish
ed
o
n
22
N
ov
em
be
r 2
01
0
on
h
ttp
://
pu
bs
.rs
c.
or
g
| do
i:1
0.1
039
/C0
NJ
004
54E
View Online / Journal Homepage / Table of Contents for this issue
This journal is c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2011 New J. Chem., 2011, 35, 292–298 293
remove the water and hydrogen chloride (the hydrolysis
product). Fresh substrates and toluene were then recharged
to the residual PEG1000-DAIL[BF4]/Fe2(SO4)3 and the mixture
was heated to react once again. The procedure was repeated 8
times in the hydrolysis of 1-(chloromethyl)-4-methoxybenzene,
and only 5.7% loss of weight was observed.
The excellent reaction results of the catalytic system suggest
that the hydrolysis reaction among 1-(chloromethyl)-4-
methoxybenzene, water, Fe2(SO4)3, toluene and PEG1000-
DAIL[BF4] has a particular catalytic process, which is
schematically depicted in Fig. 2. Before the hydrolysis, there
existed an obvious oil–water biphasic system, and the bottom
layer (water phase) consisted of PEG1000-DAIL[BF4],
Fe2(SO4)3, and water. The PEG1000-DAIL[BF4] and
Fe2(SO4)3 were dissolved completely in the aqueous medium
and the top layer (oil phase) consisted of toluene and
1-(chloromethyl)-4-methoxybenzene (substrate) (Fig. 2a).
During the process of hydrolysis, the oil–water biphasic
system disappeared and a homogeneous reaction medium
was formed (Fig. 2b). After the completion of the reaction,
the phase-separation appeared along with cooling (Fig. 2c),
and a complete oil–water biphasic system was formed again
after being cooled to room temperature (Fig. 2d). The
PEG1000-DAIL[BF4] plays a very important role in the
hydrolysis process to locally concentrate the reacting species
near them by exhibiting a temperature-dependent phase
behavior with toluene, which leads to a large increase in the
effective reactant concentration and the excellent results of the
hydrolysis reaction.
With these results in hand, we subjected other organic
halides to the hydrolysis reactions, and the results are listed
in Table 2. It is clear that various types of benzylic, allylic, and
aliphatic halides, both primary and secondary, can be
efficiently converted to the corresponding alcohols in good to
high yields (Table 2, entries 1–13). The reaction showed good
functional group tolerance, thus benzylic halides with alkyl,
Scheme 1 Hydrolysis of organic halides, epoxides, and esters and synthesis of PEGn-DAIL[anion].
D
ow
nl
oa
de
d
by
U
ni
ve
rs
ity
o
f S
ci
en
ce
a
nd
T
ec
hn
ol
og
y
of
C
hi
na
o
n
12
A
pr
il
20
12
Pu
bl
ish
ed
o
n
22
N
ov
em
be
r 2
01
0
on
h
ttp
://
pu
bs
.rs
c.
or
g
| do
i:1
0.1
039
/C0
NJ
004
54E
View Online
294 New J. Chem., 2011, 35, 292–298 This journal is c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2011
alkoxy, fluoro and nitro groups all gave high yields of the
corresponding alcohols (Table 2, entries 2–10). However, aryl
halides were less reactive, even under more drastic reaction
conditions, we did not obtain their corresponding phenols
(Table 2, entries 14 and 15). It was also observed that the
electronic nature of the substituents on the aromatic ring has
some impact on the reaction rate. Substrates with electron-
withdrawing groups (Table 2, entries 9 and 10) are less reactive
than those with electron-donating groups (Table 2, entries 2–7).
The next portion of this work involved the application of our
catalytic protocol to prepare 1,2-diols by hydrolysis of
epoxides with water. The optimal hydrolysis conditions were
found to be the same as those in the case of hydrolysis of
organic halides, and the desired 1,2-diol products were
obtained in excellent yields (Table 3). Results revealed that
our protocol can facilitate efficiently the hydrolysis reactions
of various epoxides with water. Various epoxides were
efficiently converted to the corresponding 1,2-diols in good
to excellent isolated yields using the catalytic protocol (Table 3,
entries 1–10). The epoxides such as 2-p-tolyloxirane and 2-(4-
methoxyphenyl)oxirane gave products in higher yields under
milder reaction conditions (Table 3, entries 2 and 3) than
4-(oxiran-2-yl)benzonitrile, 1-(4-(oxiran-2-yl)phenyl)ethanone,
and 2-(4-fluorophenyl)oxirane (Table 3, entries 4–6), which was
attributed to the electron-donating effect of alkyl group, that
may explain why they showed more activity for the reactions.
The final portion of this work involved the extension of our
catalytic protocol to the hydrolysis of esters to carboxylic acids
with water. As shown in Table 4, different esters were
transformed into the corresponding carboxylic acids in good
to excellent yields. Aryl esters containing electron-withdrawing
substituents in the ortho and para positions reacted slowly
(Table 4, entries 4–6) than those with electron-donating
substituents (Table 4, entries 2 and 3). Moreover, longer
reaction times or more harsh reaction conditions were
required to reach good yields for benzoic acid long chain
alkylesters (Table 4, entries 7–9), especially for entry 9.
Obviously, the PEG1000-DAIL[BF4]/Fe2(SO4)3 catalytic
system was found to be more effective in hydrolysis of
organic halides than that of both epoxides and esters, which
might be attributed to the different abilities of loss of the
corresponding leaving groups when in the hydrolysis of
organic halides, epoxides and esters with water (nucleophile).
The reaction rate of hydrolysis depended upon what was being
hydrolysed, under the same conditions, the substrate molecule
which contained a better leaving group would lead to a much
easier nucleophilic attack, and a faster reaction rate and a
higher yield were obtained.
In conclusion, we have successfully developed an efficient,
experimentally simple, and environmentally friendly protocol
for the hydrolysis of organic halides, epoxides, and esters with
water catalyzed by ferric sulfate in a PEG1000-DAIL[BF4]/
toluene temperature-dependent biphasic system. Advantages
of our protocol include simplicity of operation, high yields,
easy isolation of products, good thermoregulated biphasic
behavior of the IL, and excellent recyclability of the catalytic
Table 1 Optimization of the conditions for hydrolysis of
1-(chloromethyl)-4-methoxybenzene with watera
Entry Ionic liquid Cocatalyst Time/h %Yieldb
1 — CuSO4 7 29
2 PEG600-DAIL CuSO4 1 65
3 PEG800-DAIL CuSO4 1 73
4 PEG1000-DAIL CuSO4 1 78
5 PEG1000-DAIL[BF4] CuSO4 1 95
6 PEG1000-DAIL[PF6] CuSO4 1 92
7 PEG1000-DAIL[OTf] CuSO4 1 88
8 PEG1000-DAIL[BF4] — 2 81
9 PEG1000-DAIL[BF4] FeSO4 1 96
10 PEG1000-DAIL[BF4] Fe2(SO4)3 0.7 99
11 PEG1000-DAIL[BF4] CdSO4 2 80
12 PEG1000-DAIL[BF4] MnSO4 2 75
13 PEG1000-DAIL[BF4] ZnSO4 2 54
14 PEG1000-DAIL[BF4] Cu(OAc)2 2 91
15 PEG1000-DAIL[BF4] CuI 4 61
16 PEG1000-DAIL[BF4] FeCl3 4 66
a Reactions were carried out using 1-(chloromethyl)-4-
methoxybenzene (2 mmol), H2O (2 mL), cocatalyst (0.05 mmol), and
IL (2 mL) in toluene (2 mL) at 110 1C. b Isolated yield.
Fig. 1 Repeating hydrolysis reactions using recovered PEG1000-
DAIL[BF4]/Fe2(SO4)3.
Fig. 2 Catalytic hydrolysis process in PEG1000-DAIL[BF4]/Fe2(SO4)3.
D
ow
nl
oa
de
d
by
U
ni
ve
rs
ity
o
f S
ci
en
ce
a
nd
T
ec
hn
ol
og
y
of
C
hi
na
o
n
12
A
pr
il
20
12
Pu
bl
ish
ed
o
n
22
N
ov
em
be
r 2
01
0
on
h
ttp
://
pu
bs
.rs
c.
or
g
| do
i:1
0.1
039
/C0
NJ
004
54E
View Online
This journal is c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2011 New J. Chem., 2011, 35, 292–298 295
system. The scope, the definition of mechanism, and utility of
the catalytic system to other organic syntheses are currently
under study in our laboratory.
Experimental
All the chemicals were from commercial sources and used
without any pretreatment. All reagents were of analytical
grade. 1H NMR spectra were recorded on a Bruker 400 MHz
spectrometer using CDCl3 as the solvent with tetramethylsilane
(TMS) as an internal standard. High performance liquid
chromatography (HPLC) experiments were performed on a
liquid chromatograph (Dionex Softron GmbH, USA),
consisting of a pump (P680) and an ultraviolet-visible light
detector (UVD) system (170U). Elemental analysis was
performed on a Vario EL III instrument (Elmentar Analysen
Systeme GmbH, Germany).
Typical procedure for the preparation of ionic liquid
(PEG1000-DAIL[BF4])
(i) Preparation of intermediate 2 (according to ref. 13): a
mixture of PEG-1000 (1, 0.1 mol), pyridine (0.25 mol), and
toluene (80 mL) was stirred in a 250 mL round flask at 86 1C,
then SOCl2 (0.105 mol) was added dropwise slowly, after that
the mixture was stirred for another 18 h at 88 1C. Upon
completion, the mixture was cooled to room temperature,
then 10% HCl solution (40 mL) was added, the organic
phase appeared and was then separated by decantation, the
water phase (pyridine hydrochloride aqueous solution) was
extracted with toluene (2 � 10 mL). The combined organic
phases were washed with water (2 � 10 mL), then dried over
anhydrous Na2SO4. The solvent was removed under reduced
pressure to give 2. (ii) Preparation of intermediate 3 (according
to ref. 13 and 16): a mixture of imidazole (0.1 mol), sodium
Table 2 Hydrolysis of organic halides to alcohols with watera
Entry Substrate Time/h Product %Yieldb
1 1 96
2 0.7 97
3 0.7 99
4 0.7 99
5 0.7 95
6 0.7 96
7 0.7 98
8 1 96
9 3 92
10 3 93
Table 2 (continued )
Entry Substrate Time/h Product %Yieldb
11 1 96
12 1 95
13 1 97
14 24 —c 0
15 24 —c 0
a Reactions were carried out using organic halides (2 mmol), H2O
(2 mL), Fe2(SO4)3 (0.05 mmol), and PEG1000-DAIL[BF4] (2 mL) in
toluene (2 mL) at 110 1C. b Isolated yield. c No product was detected.
D
ow
nl
oa
de
d
by
U
ni
ve
rs
ity
o
f S
ci
en
ce
a
nd
T
ec
hn
ol
og
y
of
C
hi
na
o
n
12
A
pr
il
20
12
Pu
bl
ish
ed
o
n
22
N
ov
em
be
r 2
01
0
on
h
ttp
://
pu
bs
.rs
c.
or
g
| do
i:1
0.1
039
/C0
NJ
004
54E
View Online
296 New J. Chem., 2011, 35, 292–298 This journal is c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2011
ethoxide (0.1 mol), and ethanol (10 mL) was stirred at 70 1C for
8 h, then 2 (0.05 mol) was added into the reaction solution.
After that the mixture was stirred for another 20 h at 70 1C.
Upon completion, the mixture was filtered, then the filtrate was
extracted with ether (3 � 10 mL). The combined organic
phases were concentrated under reduced pressure to give 3.
(iii) Preparation of ionic liquid PEG1000-DAIL[BF4] 4
(according to ref. 13 and 16): 1,3-propanesultone (0.04 mol)
was added dropwise into intermediate 3 (0.02 mol) over
20 min, with vigorous stirring, then the mixture was stirred
for another 10 h at 50 1C. ThenHBF4 was added dropwise over
20 min. The final solution was stirred at 50 1C for another 8 h
to give PEG1000-DAIL[BF4] as a viscous yellowish-brown
liquid.
Typical procedure for the hydrolysis reaction (Table 2, entry 3)
To a stirred solution of 1-(chloromethyl)-4-methoxybenzene
(2 mmol), H2O (2 mL), and PEG1000-DAIL[BF4] (2 mL) in
toluene (2 mL) was added Fe2(SO4)3 (0.05 mmol) and then
stirring was continued at 110 1C for 0.7 h, the reaction progress
was monitored by HPLC. Upon completion, the mixture was
cooled to room temperature. The organic phase was separated
by decantation and dried with anhydrous sodium sulfate. Then
the crude mixture was purified by column chromatography on
silica gel to afford a colourless oil of 4-methoxybenzyl alcohol
(273.3 mg, 99% yield). The next run was performed under
identical reaction conditions.
1H-NMR (400 MHz, CDCl3): d/ppm = 1.86 (br, 1H, OH),
3.76 (s, 3H, CH3), 4.63 (s, 2H, CH2), 6.93–7.02 (m, 4H, Ar–H).
Elemental analysis %calc. (%found): C 69.49 (69.54), H 7.31
(7.30), O 23.18 (23.16).
Mesitylmethanol (Table 2, entry 7)
1H-NMR (400MHz, CDCl3): d/ppm= 1.85 (br, 1H, OH), 2.21
(s, 3H, CH3), 2.24 (s, 6H, CH3), 4.65 (s, 2H, CH2), 6.93–7.02
(s, 2H, Ar–H). Elemental analysis %calc. (%found): C 79.92
(79.96), H 9.42 (9.39), O 10.64 (10.65).
3-Phenoxypropane-1,2-diol (Table 3, entry 7)
1H-NMR (400 MHz, CDCl3): d/ppm = 3.62–3.78 (m, 5H,
CH2, CH and OH), 4.29 (d, J = 7.0 Hz, 2H, CH2), 6.97–7.06
(m, 3H, Ar–H), 7.21 (m, 2H, Ar–H). Elemental analysis %calc.
(%found): C 64.22 (64.27), H 7.20 (7.19), O 28.56 (28.54).
3-(4-Methoxyphenyl)acrylic acid (Table 4, entry 10)
1H-NMR (400MHz, CDCl3): d/ppm= 3.79 (s, 3H, CH3), 6.14
(d, J = 7.2 Hz, CH, 1H), 7.19 (d, J = 7.2 Hz, CH, 1H), 7.06
(m, Ar–H, 2H), 7.48 (m, Ar–H, 2H), 11.8–12.9 (br, COOH,
1H). Elemental analysis %calc. (%found): C 67.37 (67.41), H
5.67 (5.66), O 26.93 (26.94).
Acknowledgements
We thank the National Basic Research Program (973) of China
(No. 613740101) and Natural Science Foundation of Jiangsu
Province for support of this research.
Table 3 Hydrolysis of epoxides to 1,2-diols with watera
Entry Substrate Time/h Product %Yieldb
1 2.5 92
2 2 94
3 2 96
4 4.5 87
5 4.5 86
6 4.5 89
7 2.5 95
8 2 95
9 2 96
10 2 98
a Reactions were carried out using epoxides (2 mmol), H2O (2 mL),
Fe2(SO4)3 (0.05 mmol), and PEG1000-DAIL[BF4] (2 mL) in toluene
(2 mL) at 110 1C. b Isolated yield.
D
ow
nl
oa
de
d
by
U
ni
ve
rs
ity
o
f S
ci
en
ce
a
nd
T
ec
hn
ol
og
y
of
C
hi
na
o
n
12
A
pr
il
20
12
Pu
bl
ish
ed
o
n
22
N
ov
em
be
r 2
01
0
on
h
ttp
://
pu
bs
.rs
c.
or
g
| do
i:1
0.1
039
/C0
NJ
004
54E
View Online
This journal is c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2011 New J. Chem., 2011, 35, 292–298 297
Table 4 Hydrolysis of esters to carboxylic acids with watera
Entry Substrate Time/h Product %Yieldb
1 2 95
2 1.5 97
3 1.5 97
4 4 95
5 4 95
6 4 94