Poly(ethylene glycol) grafted onto dowex resin: An efficient, recyclable, and mild polymer-supported phase transfer catalyst for the regioselective azidolysis of epoxides in water

Article abstract of DOI:10.1021/jo801356y

(Chemical Equation Presented) In this study, an efficient method was designed to graft poly(ethylene glycol) effectively onto commercial Dowex resin. The catalytic efficiency of the copolymer obtained as a new solid-liquid phase transfer catalyst was stud

Full text of DOI:10.1021/jo801356y

Poly(ethylene glycol) Grafted onto Dowex Resin: An Efficient,
Recyclable, and Mild Polymer-Supported Phase Transfer Catalyst
for the Regioselective Azidolysis of Epoxides in Water
Ali Reza Kiasat,* Rashid Badri, Behrouz Zargar, and Soheil Sayyahi
Chemistry Department, College of Science, Chamran UniVersity, AhVaz 61357-4-3169, Iran
akiasat@scu.ac.ir
ReceiVed July 6, 2008
In this study, an efficient method was designed to graft poly(ethylene glycol) effectively onto commercial
Dowex resin. The catalytic efficiency of the copolymer obtained as a new solid-liquid phase transfer
catalyst was studied. It was proved that this organocatalyst is an efficient heterogeneous catalyst for
regioselective azidolysis of epoxide in water and gave azidohydrin in excellent yield under mild reaction
conditions. The polymeric catalyst was easily recovered by simple filtration and showed no appreciable
loss of activity when recycled several times.
Introduction
Poly(ethylene glycol) (PEG) and its derivatives are interesting
catalysts5 and solvents.6 PEGs are known to be inexpensive and
thermally stable, have almost negligible vapor pressure, and are
toxicologically innocuous and environmentally benign media
for chemical reactions.7
By considering the significance of all of the earlier studies
in general and the development of water as an eco-friendly
medium for organic reactions in particular,8 we decided to
synthesize a novel insoluble polymer-supported phase transfer
catalyst by simple grafting of PEG onto Dowex resin to form
a unique PTC complex of Dowex-PEG and thus develop an
alternative catalytic system for some transformations such as
azidolysis of epoxide.
Phase transfer catalysis (PTC) is a fascinating area of current
research interest, especially for synthetic organic chemists.1 One
practical limitation of the phase transfer method, however, is
that many of the catalysts used promote the formation of stable
emulsions. Immobilization of the phase transfer catalyst on an
insoluble polymeric matrix can provide a simple solution to this
problem.2 This technique would have considerable advantages.
Not only would the catalyst recovery and product isolation be
greatly simplified but also, owing to the three-phase nature of
the system, continuous flow methods could be employed,
making the technique particularly attractive for industrial
applications.3 Hence, graft copolymers have been extensively
studied recently because of their varied applications.4
The regioselective formation of ꢀ-azido alcohols from azi-
dolysis of epoxides is an important reaction in medicinal and
organic chemistry as these are useful synthetic intermediates
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8382 J. Org. Chem. 2008, 73, 8382–8385
10.1021/jo801356y CCC: $40.75 2008 American Chemical Society
Published on Web 10/15/2008

Poly(ethylene glycol) Grafted onto Dowex Resin
TABLE 1. Amount of PEGs with Different Molecular Weights
Supported on Dowex
SCHEME 1. Preparation of Dowex-PEGs
grafted resins
degree of immobilization
Dowex-PEG300
Dowex-PEG400
Dowex-PEG600
Dowex-PEG2000
Dowex-PEG6000
1.45
0.95
0.50
0.10<
TABLE 2. Comparison of Various Solvents in Azidolysis of
2,3-Epoxypropyl Phenyl Ether
entry
catalyst
solvent time (h)
result
1
2
3
4
5
6
Dowex-PEG300 CH2Cl2
Dowex-PEG300 CH3CN
Dowex-PEG300 THF
Dowex-PEG300 H2O
2.0
2.0
2.0
0.75
2.0
2.0
5% yield
7% yield
5% yield
completed
some diol was isolated
some diol was isolated
PEG300
Dowex
H2O
H2O
for the preparation of ꢀ-amino alcohols, vicinal diamines, natural
products, and chiral auxiliaries.9 Generally, azidohydrins are
prepared through the ring opening of epoxides using different
azides in suitable solvents.10 Even though the classic protocol11
uses sodium azide and ammonium chloride, the azidolysis
reaction requires a long reaction time (12-48 h) and the
azidohydrin is often accompanied by isomerization, epimeriza-
tion, and rearrangement of products.12 Although a few reagents
and catalysts have been reported recently for the conversion of
epoxides to ꢀ-azido alcohols,10,13 disadvantages such as long
reaction times, low yields of products, difficulty in preparation
and/or storage of reagents or catalysts, tedious workup, and, in
most cases, low regioselectivity, clearly identify a need to
introduce new methods for such functional group transformations.
TABLE 3. Investigation of Catalyst Evaluation of Grafted
Polymer
grafted resins
time (min)a
Dowex-PEG300
Dowex-PEG400
Dowex-PEG600
Dowex-PEG2000
Dowex-PEG6000
45
75
180
b
a All reaction were carried out under similar conditions. b No reaction.
with 20 mL of 0.5 M NaOH for 1 h. Then, the solutions were
titrated with 0.5 M HCl. The degree of immobilization of PEG
with different molecular weights is shown in Table 1 and clearly
indicates that Dowex-PEG300 showed the highest degree of
immobilization of PEG units on the main backbone of the resin.
Initially, the ring opening of 2,3-epoxypropyl phenyl ether
(1 mmol) with azide anion (1.2 mmol) in the presence of
Dowex-PEG300 was chosen as a model, and the role of various
solvents on the reaction system was investigated. TLC analysis
of the reaction mixture did not show completion of the reaction
in dichloromethane, chloroform, tetrahydrofuran, and acetonitrile
under reflux conditions after 2 h, but surprisingly, in water, the
reaction was completed within 45 min (Table 2). The reaction
produced 1-azido-3-phenoxypropan-2-ol in quantitative yield.
This reaction was also tested, using PEG and Dowex separately;
the reaction failed to give the expected product, but after a
prolonged reaction time, some diol was isolated.
For the sake of comparison and evaluation, we performed
azidolysis of 2,3-epoxypropyl phenyl ether (1 mmol) using the
grafted polymers as acidic phase transfer catalysts and sodium
azide (1.2 mmol) in water under reflux conditions. Among the
five kinds of polymer-supported phase transfer catalysts (3a-3e,
Scheme 1), it was found that Dowex-PEG300 had the highest
catalytic activity of the grafted polymers (Table 3). We reasoned
that this was because of the greater number of PEG units linked
to the main backbone of the resin.
Results and Discussion
A series of PEGs with molecular weights of 300, 400, 600,
2000, and 6000 Da can be easily grafted to Dowex Maraton C
resin (cat 3a-3e) in the reaction presented in Scheme 1. In the
first step, sulfonic acid functional groups of resin were converted
to sulfonyl chloride. PEG can be efficiently immobilized on the
resin by reaction of sulfonyl chloride functional groups with
PEG. The reaction is very clean and does not require any workup
procedure because the evolved HCl gas can be removed from
the reaction vessel immediately.
To determine the amount of PEG supported on the resin, the
degree of immobilization, 0.5 g of the Dowex-SO3H and
Dowex-PEG were washed with methanol, dried, and mixed
(9) (a) Horton, D.; Wander, J. D. In The Carbohydrates; Pigman, W., Horton,
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64, 6094–6096, and references therein.
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Yadav, J. S. Synthesis 2002, 15, 2254–2258. (d) Kazemi, F.; Kiasat, A. R.;
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H.; Shekarize, M. Org. Biolmol. Chem. 2003, 1, 724–727. (f) Chen, S. W.;
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120–123.
In Figure 1, the chemical structure and morphology of the
Dowex-PEG300 resin are shown by scanning electron micros-
copy (SEM). According to the obtained results, we tried to use
Dowex-PEG300 as an efficient and recoverable promoter of ring
opening of different types of epoxides by the azide ion in H2O.
To determine the optimum conditions, the conversion of 2,3-
epoxypropyl phenyl ether to the corresponding azidohydrine was
investigated in the presence of polymeric catalyst as phase
transfer catalyst in water. The optimum molar ratio of catalyst
J. Org. Chem. Vol. 73, No. 21, 2008 8383

Kiasat et al.
FIGURE 1. SEM micrograph and chemical structure of Dowex-PEG300: (a) scale bar ) 100 µm, and (b) scale bar ) 20 µm.
TABLE 4. Dowex-PEG300 Catalyzed Regioselective Ring Opening
of Epoxides
SCHEME 2. Postulated Roles of Dowex-PEG in the
Azidolysis of Epoxides
an aryl epoxide formed the product by attack at the benzylic
position. In all cases, a very clean reaction was observed and
careful examination of the 1H NMR spectra of the crude
products clearly indicated the formation of only one regioisomer
in each case (except in entry 1). The probable reason may be
that, in styrene oxide, the positive charge on the oxygen appears
to be localized on the more highly substituted benzylic carbon
leading to the major product,14 whereas in the case of aliphatic
epoxides, steric factors predominate over electronic factors,
thereby facilitating attack at the less hindered carbon atom of
the epoxide ring. Also, in the case of cyclohexene oxide, the
reaction was completely antistereoselective, and the trans
product was obtained (Table 4, entry 2). In the case of
epichlorohydrin, the diazido alcohol was produced (Table 4,
entry 3). The structures of all of the products were determined
1
from their analytical and spectral (IR, H NMR) data and by
direct comparison with authentic samples.
a Products were identified by comparison of their physical and
spectral data with those of authentic samples. b Isolated yields.
c According to GC analysis. d The molar ratio of epoxide to NaN3 was
1:2.5. e Some diol was isolated.
In the present conversion, the role of Dowex-PEG300 is
possibly to form complexes with cations, much like crown
ethers, and these complexes cause the anion to be activated. In
addition, polymeric catalyst can probably facilitate the ring
opening of the epoxide by hydrogen bonding as shown in
Scheme 2.
While developing a new method for ring opening of epoxide
using PTC,15 we recently reported PEG-SO3H as an acidic
phase transfer catalyst.16 Unfortunately, the use of recycled
PEG-SO3H shows a loss in its activity reflected in the yield of
to epoxide was found to be 0.1 g/1 mmol of epoxide. It is also
worth mentioning that Dowex-PEG300 does not suffer from
extensive mechanical degradation after operating at the high
stirring rates required by PTC conditions.
The success of this first set of experiments using
Dowex-PEG300 as a catalyst encouraged us to increase the
scope of the reaction to other epoxides (Table 4). Excellent
yields of the desired ꢀ-azido alcohols were obtained with a
reversal of regioselectivity indicating attack at the less substi-
tuted carbon of the aliphatic epoxides, while styrene oxide as
(14) Benedetti, F.; Berti, F.; Norbedo, S. Tetrahedron Lett. 1998, 39, 7971–
7974.
(15) (a) Li, J. T.; Liu, X. F. Ultrason. Sonochem. 2008, 15, 330–333. (b)
Kiasat, A. R.; Zayadi, M. Catal. Commun. 2008, 9, 2063–2067.
8384 J. Org. Chem. Vol. 73, No. 21, 2008

Poly(ethylene glycol) Grafted onto Dowex Resin
SCHEME 3. Facile Nucleophilic Ring Opening of Epoxides in the Atom Economical Method
vacuum at 50 °C. Then the polymer was refluxed with freshly
ring opening of epoxide. The most ideal synthetic methodology
could be defined as a system wherein 100% atom economy is
preserved, the solvent is recycled to the fullest extent, and the
catalyst or excess of reagent remains throughout in the solvent
medium and without losing activity for several runs. In general,
the methodology worked well independently on the nature of
the epoxide, furnishing the corresponding azido alcohols in high
yields. The Dowex-PEG300 and the additional sodium azide
(0.2 mmol) were conveniently separated from the reaction
mixture by simple extraction of product in ethyl acetate phase.
The aqueous phase was reused three consecutive times with
only a slight variation in the yields of the corresponding
products. Scheme 3 describes the facile nucleophilic ring
opening of epoxides with sodium azide in the atom economical
method.
distilled SOCl2 (5.0 mL, 67 mmol). After stirring for 6 h, the excess
unreacted thionyl chloride was distilled out. To the resulting
polymer was added a solution of PEG (5.0 mL, Mw ) 300) in dried
dichloromethane (5.0 mL), and the solution was mixed at room
temperature until no HCl was produced. The solid was filtered off
and washed thoroughly with acetone. Then the Dowex-PEG300 was
collected and dried in vacuum.
Typical Procedure for the Regioselective Ring Opening of
Epoxides. To a mixture of epoxide (1.0 mmol) and Dowex-PEG300
(0.1 g) in water (5.0 mL) was added NaN3 (1.2 mmol). The
suspension was magnetically stirred under reflux conditions for the
time shown in Table 4. After complete consumption of epoxide as
judged by TLC (using n-hexane/ethylacetate (5:1) as eluent), the
insoluble PTC was filtered off and the filtrate was extracted with
EtOAc (3 × 5). The extract was washed with water, dried over
Na2SO4, and evaporated in vacuo to give the azidohydrines in
85-96% isolated yields. For styrene oxide, further purification was
achieved by preparative TLC or by silica gel column chromatography.
To evaluate the efficiency of this method for the scaling up
experiment, transformation of 2,3-epoxypropyl phenyl ether and
cyclohexene oxide was also performed on a 100 mmol scale.
Gratifyingly, both substrates provided the corresponding azido
alcohol without appreciable decrease in the yields.
1
2-Azido-2-phenyl-1-ethanol: IR (neat) ν N3 (2102 cm-1); H
In conclusion, we have reported the first example of the use
of PEG supported on Dowex resin as an efficient and reusable
heterogeneous catalyst in the regioselective azidolysis of ep-
oxides in water. The reactions generated the corresponding
products with satisfactory yields. Moreover, the catalytic
material is easily recovered and can be recycled at least three
times without loss of activity. These results broaden the scope
of this organocatalyst as a new solid-liquid phase transfer
catalyst.
NMR (400 MHz, CDCl3) δ 1.98 (br s, 1H), 3.73 (d, 2H), 4.65 (t,
1H), 7.20-7.40 (m, 5H).
2-Azidocyclohexan-1-ol: IR (neat) ν N3 (2097 cm-1); 1H NMR
(400 MHz, CDCl3) δ 1.20-1.36 (m, 4H), 1.72-1.78 (m, 2H),
2.00-2.07 (m, 2H), 2.52 (s, 1H), 3.10-3.22 (m, 1H), 3.28-3.42
(m, 1H).
Acknowledgment. We are grateful to the Research Council
of Chamran University for financial support.
Experimental Section
Supporting Information Available: Experimental proce-
dures and characterization of some products in Table 4 and SEM
figures. This material is available free of charge via the Internet
at http://pubs.acs.org.
Typical Procedure for Grafting of the Poly(ethylene
glycol) to Dowex Maraton C. Two grams of Dowex H+ resin
(Mesh 30-40) was washed with cold methanol and dried under
(16) Kiasat, A. R.; Fallah Mehrjardi, M. Catal. Commun. 2008, 9, 1497–
1500.
JO801356Y
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