Synthesis of azidohydrins from epoxides using quaternized amino functionalized cross-linked polyacrylamide as a new polymeric phase-transfer catalyst

Article abstract of DOI:10.1016/S0040-4039(01)01891-3

Poly[N-(2-aminoethyl)acrylamido]trimethyl ammonium chloride resin was developed as a new polymeric phase-transfer catalyst. This quaternized polyacrylamide-catalyzed the regioselective ring opening of epoxides by azide ion to give azidohydrins in high yie

Full text of DOI:10.1016/S0040-4039(01)01891-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 8721–8724
Synthesis of azidohydrins from epoxides using quaternized amino
functionalized cross-linked polyacrylamide as a new
polymeric phase-transfer catalyst
B. Tamami* and H. Mahdavi
Chemistry Department, Shiraz University, Shiraz 71454, Iran
Received 10 July 2001; revised 26 September 2001; accepted 5 October 2001
Abstract—Poly[N-(2-aminoethyl)acrylamido]trimethyl ammonium chloride resin was developed as a new polymeric phase-transfer
catalyst. This quaternized polyacrylamide-catalyzed the regioselective ring opening of epoxides by azide ion to give azidohydrins
in high yield under mild conditions. © 2001 Elsevier Science Ltd. All rights reserved.
Problems associated with the phase separation of an
inorganic reagent and an organic substrate can be
overcome by the use of phase-transfer catalysts in both
compounds involve ring opening of 1,2-epoxides with
azide anion. The reactions are often carried out under
either alkaline or acidic conditions and several different
methods have been devised in order to obtain the direct
azidolysis of epoxides in the presence of sodium
1,2
homogeneous and heterogeneous forms.
Polymer-
supported catalysts are the most attractive types of
polymer-supported species for applications in organic
chemistry, because they provide great ease in separation
and recycling of the catalyst and isolation of the
12,13,15
azide.
peratures and/or long reaction times, and as side reac-
tions, isomerizations, epimerization, and
Usually these conditions require high tem-
3
,4
product. Although a polystyrene support has been
widely used for the preparation of polymer-supported
phase-transfer catalysts, its physicochemical incompati-
bility with solvents and substrates most often leads to
rearrangements may be induced by the alkaline condi-
tions of the reactions with alkali azides in these systems.
Furthermore, in recent years several novel methods
have been introduced for this kind of transformation,
for example, it has been found that sodium azide
impregnated on a calcium cation exchange Y-type zeo-
lite (CaY) induced the nucleophilic ring opening of
5
low efficiency and reactivity. The design of synthetic
polar polymeric supports such as polyacrylamide is a
significant advance. Polyacrylamide and its modified
forms have been used as cosolvent-type catalysts for
nucleophilic displacement reactions under biphase and
1
6
epoxides in aprotic solvents affording azidohydrins.
Other reported reagents are tributyltin azide without
17b
6
17a
triphase conditions, as supports for the solid-phase
solvent and promoter,
dibutyltin azide in DMF,
7
8
synthesis of peptides, for metal complexation, and for
the preparation of a number of polymer-supported
triethylaluminum/hydrogen azide as a mild and efficient
1
8a
reagent for medium to large ring cyclic epoxides,
diethylaluminium azide for the regio and stereoselective
9
reagents. Also, modified polyacrylamide grafted onto
18b
the surface of a porous nylon capsule membrane was
ring opening of 2,3-epoxyalcohols, trimethylsilylazide
10
18c
used as a phase-transfer catalyst. These supported
systems were found to have different characteristics in
terms of polarity, solvation, and reactivity compared to
in the presence of a Lewis acid, and also trimethyl-
18d
silylazide in presence of Cr (salen). In addition, it has
been reported that simple salts, such as lithium or
magnesium perchlorate, zinc or lithium triflate, and
ammonium chloride can be used as efficient catalysts
9c,11
commonly used polystyrene-supported species.
19
b-Azidoalcohols are an important class of organic com-
pounds, and they serve as precursors in the synthesis of
b-aminoalcohols, amino sugars and carbocyclic
for the azidolysis of epoxides in acetonitrile. Use of
20a
phase-transfer catalyst, and polymer-supported azide
20b
systems have also been reported for the preparation
of azidohydrins. In most of these cases, the presence of
a cation or a Lewis acid seems to be necessary to
facilitate the cleavage of epoxides. However, the afore-
mentioned methodologies are not without problems,
1
2–14
nucleosides.
The usual synthetic routes to these
*
0
Corresponding author. E-mail: tamami@chem.susc.ac.ir
040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01891-3

8
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B. Tamami, H. Mahda6i / Tetrahedron Letters 42 (2001) 8721–8724
such as difficulty in preparation and/or storage of
centage of the other regioisomer, the reaction of other
epoxides were found to be highly regioselective and
only one isomer was obtained. Also, in case of
epichlorohydrin (entry 5), the diazido-alcohol product,
and in cases of cyclic epoxides (Table 2, entries 7–8),
trans- products were obtained. Obviously, in these reac-
tions, the attack appears to be largely, if not entirely, at
the primary carbon atom of the epoxide ring. The
direction of ring opening is that characteristically
observed for reactions of monoalkyl-substituted epox-
reagents or catalysts, workup and isolation of products.
Recently we have reported the use of quaternized
amino functionalized cross-linked polyacrylamide as an
efficient polymeric phase-transfer catalyst in the synthe-
21
sis of halohydrins. In this report we describe the
results that successfully led to the development of an
efficient and simple method for the transformation of
epoxides to b-azidohydrins using quaternized amino
functionalized cross-linked polyacrylamide as an
efficient heterogeneous polymeric phase-transfer
catalyst.
ides under S 2 conditions and is probably dictated by
N
steric and electronic factors. In the reaction with sty-
rene oxide, the azide ion attacks exclusively at the
secondary carbon atom of the epoxide ring, a fact,
Polyacrylamide cross-linked with divinylbenzene (2%)
was prepared by free radical solution polymerization of
the monomer mixture in ethanol using benzoylperoxide
as an initiator and poly[N-(2-aminoethyl)acrylamide]
was obtained by the transamidation reaction of cross-
linked polyacrylamide with excess amounts of ethyl-
15a,17b,18a,19a
which is reasonably well established.
In order to get an insight into the role of poly[N-(2-
aminoethyl)acrylamido]trimethyl ammonium chloride
resin as a polymeric catalyst in this type of transforma-
tion, a series of reactions were performed on styrene
oxide with NaN3 in the presence of catalysts A–E
8
a,21
enediamine.
Poly[N-(2-aminoethyl)acrylamido]tri-
methyl ammonium chloride was prepared by the reac-
tion of poly[N-(2-aminoethyl)acrylamide] with an
excess of methyl iodide in DMF at room temperature
and subsequent exchange of the iodide anion with
chloride.
(
Table 3). Obviously, in the absence of any catalyst no
reaction occurred. The reactions proceeded in the pres-
ence of all of these catalysts (entries 2–6), however, the
rate of reaction was highest in the case of poly[N-(2-
aminoethyl)acrylamido]trimethyl ammonium chloride
resin E (entry 6).
The synthetic utility of this modified polymer was
explored by examining the reaction of epoxides with
sodium azide for the preparation of b-azidohydrins
using the polymer as a phase-transfer catalyst. The
effects of solvent and molar ratio of the polymer on the
ring opening reaction of epoxides were investigated.
The reactions were carried out in wet tetrahydroforan,
chloroform, dichloromethane, ethyl acetate, acetonitrile
and water. The last two solvents proved to be the best
In the case of poly[N(2-aminoethyl)acrylamide] (A),
tetrabutylammonium bromide (C), and Amberlyst A-26
−
[
Cl form] (D) (entries 2, 4, and 5), respectively, the
rates were almost the same, but much lower than that
of E (entry 6), and the rate when polyacrylamide (B)
(
entry 3) was used was very low. As for B, no quater-
nized site is present and the polymer is unable to act as
a phase-transfer catalyst. Entry 7 shows that a combi-
nation of species A and C lowers the reaction time
considerably compared to each one alone. All of these
experimental facts lead us to believe that poly[N-(2-
aminoethyl)acrylamido]trimethyl ammonium halide
resin (E) acts both as a catalyst for nucleophilic ring
opening reactions as well as being a phase-transfer
agent. It seems that this polymeric catalyst carrying the
nucleophile has an attracting effect on the epoxy sub-
strate and the reaction proceeds smoothly in the vicin-
ity of the catalyst. Probably the ring opening of the
epoxide is facilitated by hydrogen bonding between the
oxygen of the epoxy molecule and amidic hydrogen of
the polymer. This kind of catalytic activity is not
possible in entries 4 and 5 where species C and D act
only as phase-transfer catalysts.
(
Table 1). The optimum molar ratio of the polymeric
catalyst to epoxide was found to be 0.2:1.
The reactions of different epoxides with sodium azide
were performed effectively and in high yields in water
(
Table 2, Scheme 1). The experimental results showed
that acetonitrile can also be used as a solvent in this
reaction, however, because of its toxicity, cost and
environmental problems, water was preferred as the
most suitable solvent.
Except for the reaction of styrene oxide (entry 1) and
1,2-butene oxide (entry 6) which produce a small per-
Table 1. The effect of the solvent on the reaction of sty-
a
rene oxide with NaN using the polymeric PTC
3
In conclusion, poly[N-(2-aminoethyl)acrylamido]tri-
methyl ammonium halide resin proved to be a highly
efficient polymeric phase-transfer catalyst for regio-
selective ring opening of epoxides to azidohydrins
by azide anion. It played a special role as an elec-
trophilic catalyst, as well, for such reactions. The resin
has the inherent advantages of a solid-phase trans-
fer catalyst, including operational simplicity, filter-
ability, regenerability, and reuse. In particular,
workup of the reaction was very easy and pure prod-
ucts were isolated without any purification, and the
Entry
Solvent
Time (h)
Conversion (%)
1
2
3
4
5
6
THF
CHCl3
6
6
6
6
3
6
8b
0
CH Cl2
0
5
2
b
EtOAc
CH CN
100
100
3
H O
2
a
The molar ratio of the polymeric catalyst to styrene oxide was 0.2:1.
By GC.
b

B. Tamami, H. Mahda6i / Tetrahedron Letters 42 (2001) 8721–8724
8723
Table 2. Reaction of epoxides with NaN in the presence of poly[N-(2-aminoethyl)acrylamido]trimethyl ammonium chloride resin
3
a
as PTC
trimethyl ammonium iodide resin: poly[N-(2-amino-
ethyl)acrylamide] was prepared as described in the liter-
8a,21
ature.
equilibrated in DMF (100 ml) for 12 h. Methyl iodide
20 ml, 320 mmol) and NaOH (1 g, 25 mmol) were
Poly[N-(2-aminoethyl)acrylamide] (5 g) was
(
added and the reaction mixture stirred at room temper-
ature for 48 h. The quaternized polymer was collected
by filtration, washed several times with water and
Scheme 1.
methanol until the filtrate was free from CH I, as
3
indicated by the absence of formation of AgI with
filtered polymeric catalyst could be recovered, and after
changing to its Cl type be used several times and used
without any loss in its capacity and efficiency.
−
AgNO . Finally the polymer was washed with ether and
3
dried at 50°C under reduced pressure. Yield=8.23 g
(
69%). Capacity=3.06 mmol/g. The chloride form was
obtained by exchange of the iodide in an aqueous
solution of sodium chloride.
Reactions of epoxides with other nucleophiles under
phase-transfer conditions using this polymer and the
effect of parameters such as the nature of the alkyl
groups on the quaternized site and the spacer length are
currently under investigation.
(
B) Reaction of epoxide with sodium azide under PTC:
To a mixture of epoxide (1.0 mmol) and sodium azide
5 mmol) in water (20 ml), was added poly[N-(2-
(
aminoethyl)acrylamido]trimethyl ammonium chloride
(ꢀ0.1 g). The suspension was stirred at room tempera-
ture for the lengths of time shown in Table 2. The
progress of each reaction was monitored by TLC, using
Typical procedures
(
A) Preparation of poly[N-(2-aminoethyl)acrylamido]-

8
724
B. Tamami, H. Mahda6i / Tetrahedron Letters 42 (2001) 8721–8724
Table 3. The reaction of styrene oxide with NaN in
6. Regen, S. L.; Mehrotra, A.; Singh, A. J. Org. Chem.
1981, 46, 2183.
3
a
water
7
. Atherten, E.; Sheppard, R. C. In Peptides-Proc. Am.
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Wiley: New York, 1977; p. 503.
Entry
Catalystb
Time (h)
Temp. (°C)
Conversion
(
%)
8
. (a) Mathew, B.; Pillai, V. N. R. Polymer 1993, 34, 2650;
1
2
3
4
5
6
7
–
A
B
C
D
E
A+C
48
36
60
32
32
6
25
25
25
25
25
25
25
0
100
82
100
100
100
100
(
b) Bicak, N.; Sherington, D. C. React. Funct. Polym.
1995, 27, 155.
9. (a) Atherten, E.; Logan, C. J.; Sheppard, R. C. J. Chem.
Soc., Perkin Trans. 1 1981, 538; (b) Georg, B. K.; Pillai,
V. N. R. Macromolecules 1988, 21, 1867; (c) Mitra, S. S.;
Sreekumar, K. J. Polym. Sci. Part A, Polym. Chem. 1997,
20
3
5, 1413.
a
The molar ratio of catalyst to epoxide was 0.2:1.
1
1
0. Okahata, Y.; Ozaki, K.; Seki, T. J. Chem. Soc., Chem.
b
The type of catalysts were: A: poly[N-(2-aminoethyl)acrylamide]; B:
polyacrylamide; C: tetrabutylammonium bromide; D: Amberlyst
A26; E: poly[N-(2-aminoethyl)acrylamido]trimethyl ammonium
chloride.
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York, 1971.
CCl –ether (5:1) as eluent and/or GC. The polymer was
removed by filtration. The products were obtained
upon extraction with CH Cl . The organic solvent was
dried with anhydrous Na SO and the pure product
was obtained upon evaporation of the solvent. Product
characterization was performed using IR, H and
NMR spectroscopy.
4
1
1
2
2
2
4
1
13
14. Coe, D. M.; Myers, P. L.; Parry, D. M.; Roberts, S. M.;
C
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Acknowledgements
We are thankful to Professor N. Iranpoor for his
valuable comments and suggestions, to Shiraz Univer-
sity Research Council and Ministry of Science,
Research and Technology of Iran.
1
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