Synthesis and evaluation of poly(oxyethylene glycol) polymer (POP) supports

Article abstract of DOI:10.1021/jo020071b

Mono- and α,ω-bis-styryl-oligo(oxyethylene glycol) ethers have been constructed in an efficient two-step synthesis. From these precursors, poly(oxyethylene glycol) polymer (POP) supports of varying monomer and cross-linker composition have been produced. The swelling properties and mass-solvent uptake of these novel materials have been evaluated in a variety of solvents, demonstrating that POP supports exhibit enhanced solvent compatibilities over the commercial resins TENTAGEL, ARGO-GEL, and Merrifield's resin. The utility of POP supports in solid-phase organic chemistry has also been demonstrated successfully. It is anticipated that these high-loading polymeric supports will have generic application in the solid-phase synthesis of combinatorial libraries and the in situ screening of these libraries in the aqueous environment of a bioassay.

Full text of DOI:10.1021/jo020071b

Syn th esis a n d Eva lu a tion of P oly(oxyeth ylen e glycol) P olym er
(P OP ) Su p p or ts
Mark C. McCairn, Stephen R. Tonge, and Andrew J . Sutherland*
Department of Chemical Engineering and Applied Chemistry, Aston University,
Aston Triangle, Birmingham, B4 7ET, UK
a.j.sutherland@aston.ac.uk
Received J anuary 25, 2002
Mono- and R,ω-bis-styryl-oligo(oxyethylene glycol) ethers have been constructed in an efficient two-
step synthesis. From these precursors, poly(oxyethylene glycol) polymer (POP) supports of varying
monomer and cross-linker composition have been produced. The swelling properties and mass-
solvent uptake of these novel materials have been evaluated in a variety of solvents, demonstrating
that POP supports exhibit enhanced solvent compatibilities over the commercial resins TENTA-
GEL, ARGO-GEL, and Merrifield’s resin. The utility of POP supports in solid-phase organic
chemistry has also been demonstrated successfully. It is anticipated that these high-loading
polymeric supports will have generic application in the solid-phase synthesis of combinatorial
libraries and the in situ screening of these libraries in the aqueous environment of a bioassay.
In tr od u ction
chemically reactive sites within the resin remains con-
stant, the resin mass increases dramatically. This re-
duces the polymer loading significantly. As an alternative
to grafting long-chain PEG molecules, a recent patent
describes the grafting of short-chain PEG-based mol-
ecules onto polystyrene-based supports.6 The resultant
materials can be constructed with higher loadings of resin
than either TENTA-GEL or ARGO-GEL and, in some
instances, swell in water or alcohols.
Until recently, however, little effort has been put into
modification of the polymer matrix.3,7 Most notably,
Kurth has reported the polymerization of styrene with a
number of oligo(oxyethylene glycol) ether cross-linking
agents to generate a set of resins that swell significantly
in a range of aprotic organic solvents but are not
compatible with water.3 In addition, although the PEG-
based cross-linked resins swell more than the corre-
sponding divinylbenzene cross-linked resins, these resins
are not good supports for organic synthesis since they
possess labile benzylic ether linkages. In related work,
J anda has synthesized “organic solvent-like” polystyrene
resins by polymerizing styrene, 4-vinylbenzyl chloride,
and a tetrahydrofuran derived cross-linker.7g These
resins also exhibit excellent swelling properties in a wide
range of aprotic organic solvents. However, in contrast
to the cross-linkers utilized by Kurth, J anda’s tetrahy-
drofuran derived cross-linking agents contain only phe-
nolic ether bonds, and thus the resultant resins are
chemically robust. The J anda resins are, however, pre-
Merrifield first introduced the concept of solid-phase
organic chemistry (SPOC) by utilizing a chloromethyl-
styrene solid support for peptide synthesis.1 Predomi-
nantly, SPOC has favored the use of styrene-based resins
because of their thermal, chemical, and mechanical
stability.2 Despite their widespread use, styrene-divinyl-
benzene polymer supports (PS-DVB) exhibit limited
swelling in highly polar solvents such as water.3 Reduced
accessibility of polar reagents into the polymer matrix
often gives low-yielding on-bead reactions and, in addi-
tion, severely restricts the usage of these polymer sup-
ports in aqueous bioassays.3 In attempts to circumvent
these limitations, a variety of linkers have been attached
to PS-DVB supports to optimize their properties for
specific applications.4 While linkers modify the local
chemical environment around the reactive sites of these
resins, they do not have a significant effect upon the
intrinsic hydrophobicity of polystyrene-based resins. An
alternative approach to impart polar solvent/aqueous
compatibility is to graft larger linker units such as poly-
(ethylene glycol) (PEG), directly onto the polystyrene
support.5 PEG-containing supports of this type are avail-
able commercially as TENTA-GEL and ARGO-GEL and
have been used successfully for SPOC. A disadvantage
of the grafting process is that, while the number of
* Corresponding author. Phone: +44 (0)121 359 3611. Fax: +44
(0)121 359 4094.
(1) Merrifield, R. B. J . Am. Chem. Soc. 1963, 85, 2149.
(2) Sherrington, D. C. Chem. Commun. 1998, 2275.
(3) Wilson, M. E.; Paech, K.; J ing Zhou, W.; Kurth, M. J . J . Org.
Chem. 1998, 63, 5094.
(4) J ung, G. Combinatorial Chemistry Synthesis, Analysis, Screen-
ing, 1st ed.; Wiley-VCH: Weinheim, Germany, 1999; pp 167-228.
(5) (a) Resins and Reagents for Accelerating Synthesis and Purifica-
tion Catalogue; Argonaut Technologies: Foster City, CA, 2000; pp 40-
44. (b) Zalipsky, S.; Chang, J . L.; Albericio, F.; Barany, G. React. Polym.
1994, 22, 243.
(6) Main, B. G. PCT Publication No. WO 00/02953, 2000.
(7) (a) Itsuno, S.; Sakurai, Y.; Ito, K.; Maruyama, T.; Nakahama,
S.; Frechet, J . M. J . J . Org. Chem. 1990, 55, 304. (b) Meldal, M.
Tetrahedron Lett. 1992, 33, 3077. (c) Renil, M.; Meldal, M. Tetrahedron
Lett. 1996, 37, 6185. (d) Kamahori, K.; Ito, K.; Itsuno, S. J . Org. Chem.
1996, 61, 8321. (e) Buchardt, J .; Meldal, M. Tetrahedron Lett. 1998,
39, 8695. (f) Groth, T.; Grotli, M.; Lubell, W. D.; Miranda, L. P.; Meldal,
M. J . Chem. Soc., Perkin Trans. 1 2000, 24, 4258. (g) Toy, P. H.; J anda,
K. D. Tetrahedron Lett. 1999, 40, 6329.
10.1021/jo020071b CCC: $22.00 © 2002 American Chemical Society
Published on Web 06/17/2002
J . Org. Chem. 2002, 67, 4847-4855
4847

McCairn et al.
SCHEME 1
dominantly polystyrene-based and thus not suitable for
use in aqueous environments.
We wished to develop a set of high-loading polymeric
supports that lacked reactive chemical linkages such as
benzylic ethers and that would swell significantly in both
aqueous and organic solvents. These supports are in-
tended for use in SPOC and subsequent in situ on-
support assay in aqueous media. PEG is chemically
robust and can impart both organic and aqueous compat-
ibility onto polymers.3,5-7 Consequently, a series of PEG-
based polymeric supports that contained uniformly dis-
tributed functional groups within a chemically inert
polymer matrix were required for evaluation purposes.
Herein is reported a facile two-step synthesis of mono-
and bis-styrene-functionalized oligo(oxyethylene glycol)
ethers. The polymerization of these monomers to produce
a series of polymers of varying monomer composition,
molar percentage cross-linking (%XL), and ethylene oxide
chain length is described. In addition, the swelling
properties and mass-solvent uptake versus time of these
novel POP supports in DCM, DMF, THF, toluene, and
water are compared with those of the commercial resins,
Merrifield’s resin, TENTA-GEL, and ARGO-GEL.
SCHEME 2
Resu lts a n d Discu ssion
Syn th esis of P EG-Ba sed Mon om er s a n d Cr oss-
Lin k er s. To enable construction of the PEG-based
polymeric supports, a number of mono- and bis-polymer-
izable oligo(oxyethylene glycol) ethers were required.
Styrene was chosen as the desired polymerizable unit for
its compatibility with the scintillant-containing mono-
mers used routinely in our laboratories.8 In a synthesis
of crown ethers, Nishimura utilized bis-tosyl PEG deriva-
tives in a three-step synthesis of two bis-styrene-func-
tionalized oligo(oxyethylene glycol) ethers.9 Since these
styrene-containing ethers did not contain benzylic ether
linkages, we elected to use one of them, R,ω-bis-styryl-
pentaethylene glycol 4, as a cross-linking agent for our
polymer supports. A novel one-step route to this target
was devised on the basis of methodology previously
described by J anda.7g Commercial 4-acetoxystyrene was
treated with potassium hydroxide in the presence of
commercial penta(ethylene glycol) di-p-toluenesulfonate
2. This one-pot hydrolysis and subsequent in situ cou-
pling reaction proceeded smoothly, giving the desired
target 4 in good yield. Tri(ethylene glycol) di-p-toluene-
sulfonate 1, readily synthesized from toluenesulfonyl
chloride and tri(ethylene glycol), also underwent this one-
step hydrolysis-coupling procedure giving cross-linking
agent 3 (Scheme 1).
production of monomers.10 In addition, the synthetic
methodology used to construct such molecules is non-
trivial.11 Consequently, a facile and cost-effective route
to monostyrene-functionalized oligo(oxyethylene glycol)
ethers was required.
The synthesis of oligo(oxyethylene glycol) mono-p-
toluenesulfonates is well documented.12 Specifically,
hexaethylene glycol was reacted with toluenesulfonyl
chloride utilizing the methodology described by Brjesson
and Welch.12b However, the workup procedure was modi-
fied to preclude the need for purification by column
chromatography. A simple extraction procedure gave
pure samples (as assessed by NMR) of both hexaethylene
glycol mono-p-toluenesulfonate (5) and excess, unreacted
hexaethylene glycol in excellent yields. This workup
procedure also proved to be extremely effective in the
synthesis of poly(oxyethylene glycol)400 mono-p-toluene-
sulfonate 6. With multigram quantities of monotosylates
5 and 6 readily and cheaply available, we wished to
investigate if the one-pot hydrolysis-coupling procedure
utilized in the construction of the cross-linkers could be
extended to the generation of monostyrenic-PEG despite
the presence of an unprotected primary hydroxyl group.
Again, the reaction with 4-acetoxystyrene proceeded
smoothly giving both monostyryl-hexaethylene glycol 7
and monostyryl-poly(oxyethylene glycol)400 8 (Scheme
2).
PEG-based monomers containing both a polymerizable
styrene unit and chemical functionality to enable the
generation of chemically reactive supports were also
required. While bis-functionalized PEG is available or
else readily accessible, commercial heterofunctionalized
PEG is prohibitively expensive for routine large-scale
P olym er iza t ion of P E G-Ba sed Mon om er s a n d
Cr oss-Lin k er s. Microscale suspension polymerization of
(8) (a) Clapham, B.; Sutherland, A. J . Tetrahedron Lett. 2000, 41,
2253. (b) Clapham, B.; Sutherland, A. J . Tetrahedron Lett. 2000, 41,
2257. (c) Clapham, B.; Sutherland, A. J . PCT Publication No. WO 00/
20475, 2000. (d) Clapham, B.; Sutherland, A. J . J . Org. Chem. 2001,
66, 9033.
(9) Inokuma, S.; Yamamoto, T.; Nishimura, J . Tetrahedron Lett.
1990, 31, 97.
(10) Shearwater Corp. http://www.swpolymers.com, (accessed J an
2002).
(11) Reed, N. N.; J anda, K. D. J . Org. Chem. 2000, 65, 5843.
(12) (a) Cornforth, J . W.; Morgan, E. D.; Potts, K. T.; Rees, R. J . W.
Tetrahedron. 1973, 29, 1659. (b) Borjesson, L.; Welch, C. J . Acta Chem.
Scand. 1991, 45, 621.
4848 J . Org. Chem., Vol. 67, No. 14, 2002

Poly(Oxyethylene Glycol) Polymer (POP) Supports
F IGURE 1. Graph showing the percentage of volume change of polymers 9-16, Merrifield’s resin (M), TENTA-GEL (T), and
ARGO-GEL (A) upon exposure to water, DMF, and toluene.
SCHEME 3
styrene cross-linked with 2, 14, and 20 mol % bis-styryl-
penta(oxyethylene glycol) ether 4 gave beaded products
9-11, respectively. These materials were required to
indicate what extent of cross-linking by a PEG-based
cross-linking agent would be preferable for good solvent
compatibility. To enable direct comparison of these resins,
no porogen was employed in the construction of the more
highly cross-linked resins 10 and 11. Microscale suspen-
sion polymerization of styrene cross-linked with 2 mol
% bis-styryl-tri(oxyethylene glycol) ether 3 gave resin 12.
This resin was required for comparison with resin 9 to
enable the effect of the PEG chain length of the cross-
linking agent upon solvent compatibility to be evaluated.
In all cases, a monomer to bulk-phase ratio of 1:10 and
a mole percent fraction of AIBN of 0.8% was used as
related work had shown that these amounts give good
yields of beaded product.8a
The miscibility of monostyryl-oligo(oxyethylene glycol)
monomers 7 and 8 with 1% PVA solution prompted their
bulk polymerization with 2 mol % of either PEG-based
cross-linking agent 4 or DVB to give gel-like polymers
13-16 (Scheme 3). These materials were required to
establish whether it was preferable, in terms of general
solvent compatibility, to combine a PEG-based monomer
and cross-linker or a PEG-based monomer and a styryl-
based cross-linker.
Solven t Sw ellin g Assa y of P olym er s. Polymers
9-16, constructed from the PEG-containing monomers
and cross-linkers, were evaluated for their swelling
properties in a range of solvents. A syringe-based solvent
swelling assay with considerable literature precedent was
employed.3,7e In this manner, the percentage of volume
increase of each polymer was measured in water, DMF,
and toluene. For comparative purposes, commercial
samples of Merrifield’s resin, TENTA-GEL, and ARGO-
GEL were evaluated in an identical fashion.
Figure 1 clearly shows that polymers 14-16, contain-
ing a PEG-based monomer, swell far more in water than
all of the other polymer supports, most notably TENTA-
GEL and ARGO-GEL, which are sold commercially as
aqueous compatible supports. The predominantly styrene-
based polymers, Merrifield’s resin, and styrene-PEG-
cross-linked resins 9-12 fail to show any significant
swelling. A similar trend is observed for DMF, but
interestingly, the swelling properties of 14-16 in toluene
are very similar to those observed for all of the other
polymers. As expected and in agreement with another
similar study,3 resins 9-11 exhibit decreasing swelling
characteristics with increasing degrees of cross-linking
in DMF and toluene (Figure 1). Similarly, a comparison
of the degree of swelling of resins 9 and 12 indicates that
increasing the length of the PEG-based cross-linker, from
triethylene glycol to pentaethylene glycol, results in
increased swelling of the resin in DMF and toluene.
Polymers 14-16 had the best swelling characteristics
in water and thus seemed the most likely candidates for
use in on-support aqueous-based assays. Consequently,
these polymers were further evaluated for their compat-
ibility with DCM and THF for application in solid-phase
peptide chemistry (SPPC). For comparative purposes,
Merrifield’s resin, TENTA-GEL, and ARGO-GEL were
also evaluated in these solvents. Again, polymers 14-
16 exhibited excellent compatibility with both solvents
and swelled to far greater extents than the commercial
controls (Figure 2).
Ma ss-Solven t Up ta k e Assa y. The internal matrix of
polymers 14-16 has been tailored with the specific
intention of giving an increased surface energy in com-
J . Org. Chem, Vol. 67, No. 14, 2002 4849

McCairn et al.
F IGURE 2. Graph showing the percentage of volume change of polymers 14-16, Merrifield’s resin (M), TENTA-GEL (T), and
ARGO-GEL (A) upon exposure to DCM and THF.
F IGURE 3. Mass-water uptake versus time of polymers 14-16 relative to that of commercial resins and a blank control.
parison to those of the commercial resins. The effect of
increasing the surface energy of a polymer is to create a
thermodynamically unfavorable solid/air interface, which
causes rapid and complete wetting by spontaneous
penetration of high surface energy solvents such as water
into the polymer matrix.13 Although solvent swelling
assays give an insight into the site accessibility of a
polymer, we were also interested in quantifying the
amount of solvent penetrating the matrix of polymers
14-16. Conventionally, the wetting of nonporous surfaces
and porous solid powders by liquids can be quantified
by contact angle measurements13,14 and the Washburn
technique,14,15 respectively. Unfortunately, neither tech-
nique can be used to study gel-type polymers since
swelling of the polymer necessarily causes the contact
surface between the liquid and solid to vary. Conse-
quently, we elected to study the PEG-based polymers 14-
16 using a mass-solvent uptake assay. The assay involved
bringing a solvent just into contact with the surface of a
polymer sample so that the solvent penetrates the
polymer matrix through capillary action. The amount of
solvent penetrating the polymer matrix can be quantified
using a microbalance. Recording a mass reading at fixed
time intervals allows a time-dependent solvation profile
to be obtained for the polymer sample. In addition, the
mass of solvent imbibed by the polymer sample can also
be used to calculate the volume of solvent imbibed by the
polymer at any time. To the best of our knowledge, this
assay represents the first example whereby chemically
functionalized gel-type polymers, specifically designed for
use in SPOC, have had their solvent compatibilities and
swell kinetics evaluated in this manner.
Ma ss-Wa ter Up ta k e Assa y of P OP Su p p or ts. Equal
aliquots of each of the PEG-based polymers 14-16 and
the commercial resins TENTA-GEL, ARGO-GEL, and
Merrifield’s resin were analyzed for mass-water uptake
(Figure 3). Figure 3 shows clearly that the final mass-
solvent uptake values for each of the polymers 14-16
are about twice those of TENTA-GEL and ARGO-GEL
resins. The mass-solvent uptake versus time profile also
demonstrates that Merrifield’s resin is completely hy-
drophobic. In addition, the profiles obtained for TENTA-
GEL and ARGO-GEL resins plateau faster than those
obtained for polymers 14-16. A possible explanation for
(13) Shaw, D. J . Introduction to Colloid and Surface Chemistry, 4th
ed.; Butterworth-Heinemann, Ltd.: Oxford, 1992.
(14) Rulison, C. Kru¨ss Technical Note #302. 1966 (www.kruss.de;
e-mail. info@kruss.de) (accessed J an 2002).
(15) Washburn, E. W. Phys. Rev. 1921, 17, 374.-
4850 J . Org. Chem., Vol. 67, No. 14, 2002

Poly(Oxyethylene Glycol) Polymer (POP) Supports
F IGURE 4. Mass-DMF uptake versus time of polymers 14-16 relative to that of commercial resins and a blank control.
this observation is that there is rapid solvation of the
grafted PEG-containing regions of TENTA-GEL and
ARGO-GEL and that, subsequently, there is little if any
solvation of the hydrophobic polystyrene backbones of
these resins. In contrast, after the peripheral PEG
surfaces of polymers 14-16 have been solvated rapidly,
it appears that more time is required for complete solvent
penetration to the PEG-containing cores of these poly-
mers.
Although polymer 13 takes up a mass of water similar
to that taken up by TENTA-GEL and ARGO-GEL (data
not shown), replacement of the DVB cross-linker in
polymer 13 with R,ω-bis-styryl-pentaethylene glycol 4
gives polymer 15 and results in a polymer with a
dramatically increased mass-water uptake that is far
greater than those of both commercial resins. Similarly,
replacement of the monostyryl-hexaethylene glycol mono-
mer 7 in polymer 13 with monostyryl-poly(oxyethylene
glycol)400 8 gives polymer 14, which again exhibits a
dramatically increased mass-water uptake. In summary,
incorporating a PEG chain into the cross-linker or
increasing the PEG chain length of the monomer results
in polymers with a greater mass-water uptake. In addi-
tion, since polymer 14 (DVB cross-linker; monostyryl-
poly(oxyethylene glycol)400 monomer 8) takes up a greater
mass of water than polymer 15 (R,ω-bis-styryl-pentaeth-
ylene glycol 4 cross-linker; monostyryl-hexaethylene
glycol 7), the importance of the PEG length of the
monomer appears to outweigh the effects of the small
amount of cross-linker incorporated in gel-type supports
such as these.
controls. Both of these results are presumably a conse-
quence of the greater solvent accessibility toward a PEG
cross-linked matrix compared with that of the DVB cross-
linked styrene cores of ARGO-GEL and TENTA-GEL. As
with the mass-solvent uptake results obtained using
water, the profiles obtained for TENTA-GEL and ARGO-
GEL resins plateau faster than those obtained for
polymers 14-16. In addition, and in complete contrast
to the aqueous study, the mass-DMF uptake profile
obtained for Merrifield’s resin is very similar to that
obtained for TENTA GEL in DMF.
Ma ss-Tolu en e Up t a k e St u d y of P OP Su p p or t s.
The profiles obtained from the rate-toluene uptake assay
indicate that the mass-toluene uptake decreases in the
order Merrifield’s resin, TENTA-GEL/ARGO-GEL, 14/15/
16 (Figure 5). This order reflects the hydrophobicity of
each class of polymer studied and consolidates the view
of Merrifield’s resin behaving as a polystyrene resin,
TENTAGEL and ARGO-GEL behaving as polystyrene
resins with PEG grafts, and finally, the POP supports
behaving predominantly as PEG-based supports with
styryl grafts. Interestingly, such subtleties are less
apparent in the solvent swelling assay where all of the
polymers evaluated give relatively similar swelling vol-
umes in toluene.
SP P C on P OP Su p p or t s. Having established that
POP supports 14-16 were compatible with a wide range
of solvents of differing polarities, we wished to evaluate
their utility as supports for SPOC. Accordingly, we
elected to carry out two successive couplings of Fmoc-
Gly-OH to the pendant hydroxyl functionalities within
the POP supports. In each case, a standard Fmoc release
assay16 was used to monitor the extent of reaction. After
the first round of couplings, the loadings of the three POP
supports 14-16 were found to be 0.65, 0.68, and 0.57
mmol/g, respectively. While somewhat lower than the
theoretical loadings calculated for these supports (Table
1), these experimentally determined values are still
significantly higher than the theoretical loadings reported
Ma ss-DMF Up ta k e Stu d y of P OP Su p p or ts. In a
manner identical to that of the aqueous study, POP
supports 14-16 and commercial resins TENTA-GEL,
ARGO-GEL, and Merrifield’s resin had their mass-
solvent uptake versus time measured in DMF (Figure
4). The final mass-DMF uptake of polymers 14-16 is
approximately double that of commercial Merrifield’s
resin, TENTA-GEL, and ARGO-GEL. This finding con-
solidates the solvent swelling assay results (Figure 1b),
which showed that in DMF, polymers 14-16 swell to
about three times the volume of the commercial polymer
(16) NovaBiochem Catalog and Peptide Synthesis Handbook; Nova-
Biochem: La J olla, CA, 1998; p S37.
J . Org. Chem, Vol. 67, No. 14, 2002 4851

McCairn et al.
F IGURE 5. Mass-toluene uptake versus time of polymers 14-16 relative to that of commercial resins and a blank control.
TABLE 1. Th eor etica l a n d Exp er im en ta lly Deter m in ed
Loa d in gs of P OP Su p p or ts 14-16 a fter Tw o Su ccessive
Rou n d s of F m oc-Gly-OH Cou p lin g
supports 14-16, exhibiting superior aqueous compat-
ibility relative to the commercial resins TENTA-GEL and
ARGO-GEL, were utilized successfully as supports for
SPPC.
a
loading (mmol/g-1
coupling 1
)
POP support
theoretical
coupling 2
We intend to exploit the exceptional compatibility of
these polymeric supports with both organic and aqueous
solvents in future work. Currently, we are attempting
to construct POP supports that incorporate scintillant
molecules covalently. These materials will then be used
for the organic synthesis of polymer-supported libraries
to be screened in situ and under aqueous conditions for
biological activity.
14
15
16
1.92
2.53
1.90
0.65 (34%)
0.68 (27%)
0.57 (30%)
0.41 (63%)
0.43 (63%)
0.44 (77%)
a
Each experimental loading was established using a standard
Fmoc release assay.16 The numbers in brackets refer to the yield
of each coupling reaction. The yield for coupling 2 was calculated
using the loading of the support established in coupling 1.
Theoretical loadings were calculated from the monomer composi-
tions used in the construction of the supports.
Exp er im en ta l Section
for the commercial samples of ARGO GEL and TENTA
GEL used in this study, 0.47 and 0.28 mmol/g, respec-
tively. In addition, the second round of Fmoc-Gly-OH
couplings gave average yields of 68%. This encouraging
result indicates that POP supports are well suited for
use in SPOC.
Gen er a l In for m a tion . All reactions involving moisture-
sensitive reagents were conducted in oven dried (120 °C)
glassware. Dichloromethane (CH2Cl2), tri(ethylene glycol), and
triethylamine were distilled from calcium hydride. Hexa-
(ethylene glycol) and poly(oxyethylene glycol)400 were heated
at 120 °C under high vacuum for 1 h. All other reagents were
used as received from commercial suppliers. ARGO-GEL-OH
(0.47 mmol/g), Merrifield’s resin 2% DVB (100-200 mesh, 0.89
mmol/g), and TENTA-GEL-OH resin (0.27 mmol/g) were
purchased commercially. An aqueous solution of PVA refers
to a 1 wt %/wt aqueous solution of poly(vinyl alcohol) (87-
89% hydrolyzed, average MW 85 000-146 000). All reaction
mixtures were stirred magnetically unless otherwise stated.
Where appropriate, reactions were monitored by thin-layer
chromatography using silica gel 60 F254 precoated glass plates,
which were visualized with UV light and then developed using
either iodine, a solution of 10% phosphomolybdic acid in
ethanol, or an aqueous solution of potassium permanganate.
Flash column chromatography was carried out using silica gel
60 (0.035-0.070 µm, 220-440 mesh). The mass-solvent uptake
assays (described in General Procedure 3) were performed
Con clu sion s
In summary, a one-step synthetic procedure has been
utilized to synthesize pure heterofunctionalized oligo-
(oxyethylene glycol) ethers. A simple extraction procedure
was used to purify these compounds and also enabled the
facile recovery of excess oligo(oxyethylene glycol) ether
starting materials. The orthogonally functionalized ma-
terials together with doubly functionalized oligo(oxyeth-
ylene glycol) ethers were converted, in a one-pot reaction,
into mono- and bis-styryl-oligo(oxyethylene glycol) ethers,
respectively. Polymerization of these monomers and
cross-linkers generated a range of novel polymeric ma-
terials. Initially, the swelling properties of these materi-
als were evaluated, in a variety of solvents, by using a
conventional solvent swelling assay. The actual mass of
solvent imbibed by the polymers was then quantified
using a novel mass-solvent uptake assay. These studies
demonstrate successfully that POP supports are readily
compatible with both water and a range of organic
solvents with widely differing polarities. Finally, POP
1
using a conventional microbalance. For H NMR and 13C NMR
spectra, deuterated chloroform was used as the solvent and
chemical shift values (δ) are reported in parts per million
relative to the residual signals of this solvent (δ 7.24 for 1H
and δ 77.0 for 13C). Coupling constants are reported in hertz.
13C NMR spectra were recorded using the PENDANT pro-
gram.17 Low-resolution mass spectra were recorded with an
ion-trap spectrometer using atmospheric pressure chemical
ionization (APCI). High-resolution mass spectra were recorded
4852 J . Org. Chem., Vol. 67, No. 14, 2002

Poly(Oxyethylene Glycol) Polymer (POP) Supports
by Mr. Peter Ashton (School of Chemistry, Birmingham
University) using an electrospray mode with a mobile phase
of methanol (200 µL/min) and a lock mass to correct the mass
scale. Elemental analyses were performed by Medac, Ltd.,
Brunel Science Center, Cooper’s Hill Lane, Engelfield Green,
Egham, Surrey, UK. Infrared spectra were recorded as either
a thin film/gel pressed between two sodium chloride plates or
as a solid suspended in a potassium bromide disk. Melting
points (mp) are uncorrected.
Gen er a l P r oced u r e 1 (GP 1): Micr osca le Su sp en sion
P olym er iza tion . A monomer and cross-linking monomer
were stirred together for 15 min at room temperature. AIBN
(0.76 equiv) was added and the resultant mixture stirred for
an additional 10 min. The monomer mixture (∼1.0-1.5 mL)
was added to a stirred aqueous solution of PVA (10 mL) under
a nitrogen atmosphere and the resultant suspension stirred
for 30 min. The temperature was increased to 72 °C and
stirring continued for an additional 4 h. The mixture was
cooled to room temperature and the polymeric product collected
by filtration. The beaded polymeric product was washed with
distilled water (3 × 50 mL), MeOH (50 mL), 1/1 MeOH/THF
(50 mL), THF (50 mL), and MeOH (50 mL) and then dried to
a constant mass.
Tr i(eth ylen e glycol) Di-p-tolu en esu lfon a te (1). A solu-
tion of tosyl chloride (TsCl) (21.643 g, 111.3 mmol) in CH2Cl2
(100 mL) was added dropwise over 2 h to an ice-cooled solution
of tri(ethylene glycol) (5.00 mL, 37.1 mmol), triethylamine (31.3
mL, 222.5 mmol), and DMAP (0.0458 g, 0.37 mmol) in CH2Cl2
(200 mL) and the resultant mixture left to stir overnight while
warming to room temperature. The reaction mixture was
washed with distilled water (2 × 200 mL), saturated sodium
bicarbonate solution (2 × 100 mL), and saturated citric acid
solution (2 × 100 mL), dried over anhydrous sodium sulfate,
and concentrated under reduced pressure to give tri(ethylene
glycol) di-p-toluenesulfonate 1 as a pale yellow oil (15.107 g,
89%), which was used in subsequent reactions without further
purification: IR (thin film) νmax 2877, 1597, 1497, 1450, 1354,
1
1176 cm-1; H NMR (300 MHz, CDCl3) δH 2.40 (6H, s), 3.48
(4H, s), 3.61 (4H, t, J ) 3.0), 4.10 (4H, t, J ) 3.0), 7.31 (4H, d,
J ) 9.0), 7.75 (4H, d, J ) 6.0); 13C NMR (75 MHz, CDCl3,
PENDANT) δC 21.7, 69.1, 69.6, 71.0, 128.6, 130.6, 133.0, 145.7;
LRMS (APCI) m/z 459 (M + H+); HRMS (EI) m/z 481.0967 (M
+ Na+), calcd for C20H26O8NaS2 481.0957.
r,ω-Bis-styr yl-tr i(eth ylen e glycol) (3). 4-Acetoxystyrene
(1.00 mL, 6.3 mmol) was added to a solution of potassium
hydroxide (0.524 g, 7.94 mmol) dissolved in EtOH (12.5 mL)
and the resultant mixture stirred at room temperature for 1
h. A solution of sodium ethoxide (0.548 g, 7.73 mmol) in EtOH
(13.15 mL) was added and the resultant mixture brought to
reflux for 1 h. A solution of tri(ethylene glycol) di-p-toluene-
sulfonate 1 (1.437 g, 3.134 mmol) in EtOH (39.50 mL) was
added and the reaction mixture subsequently refluxed over-
night. The reaction mixture was concentrated under reduced
pressure, suspended in distilled water (50 mL), and extracted
with Et2O (3 × 100 mL). The combined organic fractions were
dried over anhydrous sodium sulfate and concentrated under
reduced pressure. Flash column chromatography (20% v/v
ethyl acetate in hexanes) gave R,ω-bis-styryl-tri(ethylene
glycol) 3 as a white solid (0.342 g, 31%): mp 68-69 °C; IR
Gen er a l P r oced u r e 2 (GP 2): Bu lk P olym er iza tion . A
functionalized monomer, cross-linking monomer, and AIBN
(0.76 equiv) were placed into a glass vial (1.5 mL). The vial
was held in an ultrasound bath for 2 min. Nitrogen gas was
bubbled through the monomer mixture for 5 min, and the vial
was then placed in an oven at 60 °C overnight. The resulting
polymer was washed with MeOH (30 mL), 1/1 MeOH/THF (30
mL), THF (30 mL), and MeOH (30 mL) and then dried to a
constant mass.
Gen er a l P r oced u r e 3 (GP 3): Ma ss-Solven t Up t a k e
Stu d y. The polymer (∼25 mg) was packed into the bottom of
a
polypropylene disposable syringe (1 mL), with the tip
removed, housing a nylon frit (0.45 µm). The syringe was
suspended from a microbalance and the balance reading set
at zero. A reservoir containing solvent was placed below the
syringe and raised until the solvent was just brought into
contact with the bottom of the syringe. A mass reading was
recorded every 2 s. When the solvent was water, the surface
tension of the water (72.3 mN/m) was lowered below that of
the plastic syringe and frit assembly by addition of TWEEN
20 (1% v/v). For each solvent studied, a blank control assay
was carried out. This procedure was identical in every respect
to that described above except that no polymer sample was
placed in the syringe. This procedure allowed for the “wetting”
of the syringe/frit assembly by the solvent to be taken into
account.
(thin film) νmax 3085, 3041, 2975, 2934, 2903, 1626, 1605 cm-1
;
1H NMR (300 MHz, CDCl3) δH 3.72 (4H, s), 3.83 (4H, t, J )
4.2), 4.09 (4H, t, J ) 4.0), 5.13 (2H, d, J ) 11.0), 5.61 (2H, d,
J ) 17.5), 6.66 (2H, dd, J ) 17.5, 11.0), 6.87 (4H, d, J ) 8.4),
7.32 (4H, d, J ) 8.4); 13C NMR (75 MHz, CDCl3, PENDANT)
δC 67.2, 69.5, 70.6, 111.3, 114.4, 127.1, 130.3, 136.0, 158.4;
LRMS (APCI) m/z 355 (M + H+); HRMS (EI) m/z 377.1731 (M
+ Na+), calcd for C22H26O4Na 377.1729. Anal. Calcd for
C
22H26O4: C, 74.6; H, 7.4; O, 18.0. Found: C, 74.4; H, 7.5; O,
18.1.
r,ω-Bis-styr yl-p en ta (eth ylen e glycol) (4). According to
the procedure described for R,ω-bis-styryl-tri(ethylene glycol)
3, 4-acetoxystyrene (2.8 mL, 17.4 mmol) was reacted sequen-
tially with ethanolic solutions of potassium hydroxide (1.452
g, 22.0 mmol) and sodium ethoxide (1.518 g, 21.42 mmol). An
ethanolic solution of penta(ethylene glycol) di-p-toluene-
sulfonate 2 (5.00 g, 8.68 mmol) was then added to the refluxing
reaction mixture to give R,ω-bis-styryl-penta(ethylene glycol)
4, after flash column chromatography (60% v/v ethyl acetate
in hexanes), as a white solid (1.818 g, 48%): mp 73-74 °C; IR
(thin film) νmax 3078, 3042, 2971, 2936, 2900, 2860, 1626, 1604,
Gen er a l P r oced u r e 4 (GP 4): F m oc-Gly-OH Cou p lin g
to P olym er Su p p or ts. 2,6-Dichlorobenzoyl chloride (2.9
equiv) and pyridine (6 equiv) were added to the polymer (1
equiv) and Fmoc-Gly-OH (3 equiv) in DMF (35 mL/g), and the
resultant mixture was stirred overnight. The polymer was
collected by filtration and washed in situ with DCM (3 × 30
mL) and methanol (3 × 30 mL). The Fmoc-Gly-OH derived
polymer was predried under suction before being placed in an
oven at 60 °C overnight and dried to a constant mass.
1
1511, 1456, 1110 cm-1; H NMR (300 MHz, CDCl3) δH 3.62-
Gen er a l P r oced u r e 5 (GP 5): F m oc Relea se Assa y.16
A
3.65 (12H, m), 3.78 (4H, t, J ) 4.6), 4.06 (4H, t, J ) 4.6), 5.09
(2H, d, J ) 11.0), 5.57 (2H, d, J ) 17.7), 6.62 (2H, dd, J )
17.5, 11.0), 6.83 (4H, d, J ) 8.6), 7.29 (4H, d, J ) 8.6); 13C
NMR (75 MHz, CDCl3, PENDANT) δC 63.4, 67.3, 69.5, 70.5,
70.6, 111.4, 114.5, 127.1, 130.4, 136.0, 158.4; LRMS (APCI)
m/z 443 (M + H+); HRMS (EI) m/z 465.2264 (M + Na+), calcd
for C26H34O6Na 465.2253.
polymer sample of approximately 1 mg was weighed accurately
into a sample vial. A 20% solution of piperidine in DMF (3.00
mL) was added to the vial and the resultant suspension
agitated using a Pasteur pipet. The suspension in the vial was
filtered through a plug of cotton wool into a quartz cuvette.
The absorption of the Fmoc/piperidine adduct was measured
at 290 nm against a 20% piperidine/DMF blank. The above
protocol was repeated four times for each polymer sample and
the average absorbance per mg of each sample calculated. The
loading (mmol/g) of each polymer was determined by dividing
the average absorbance per mg at 290 nm by 1.65.
Hexa (eth ylen e glycol) Mon o-p-tolu en esu lfon a te (5).
According to the procedure described for tri(ethylene glycol)
di-p-toluenesulfonate 1, a solution of TsCl (9.970 g, 0.051 mol)
in CH2Cl2 (75 mL) was added to a solution of hexa(ethylene
glycol) (60.390 g, 0.205 mol), triethylamine (28.90 mL, 0.21
mol), and DMAP (0.316 g, 2.56 mmol) in CH2Cl2 (150 mL) to
give hexa(ethylene glycol) mono-p-toluenesulfonate 5 as a pale
(17) Homer, J .; Perry, M. C. J . Chem. Soc., Chem. Commun. 1994,
373.
J . Org. Chem, Vol. 67, No. 14, 2002 4853

McCairn et al.
yellow oil (20.403 g, 92%), which was used in subsequent
dd, J ) 10.8, 17.5), 6.69 (2H, d, J ) 8.4), 7.14 (2H, d, J ) 8.6);
13C NMR (75 MHz, CDCl3, PENDANT) δC 60.9, 63.0, 66.9, 69.1,
69.7, 69.9, 70.1, 72.1, 111.0, 114.1, 126.8, 129.9, 135.6, 158.0;
LRMS (APCI) m/z 517 (100, [M + H]+), 473 (82, [M -
(C2H4O)]+), 429 (26, [M - 2(C2H4O)]+); HRMS (EI) m/z
451.2326 [29, (M - 2(C2H4O) + Na+], calcd for C22H36O8Na
451.2308; 495.2579 [89, (M - (C2H4O) + Na+], calcd for
reactions without further purification: IR (thin film) νmax 3478,
2874, 1598, 1097 cm-1 1H NMR (300 MHz, CDCl3) δH 2.36
;
(3H, s), 2.98 (1H, s), 3.51-3.62 (22H, m), 4.08 (2H, t, J ) 4.7),
7.26 (2H, d, J ) 8.2), 7.71 (2H, d, J ) 8.2); 13C NMR (75 MHz,
CDCl3, PENDANT) δC 21.5, 61.5, 68.6, 69.2, 70.1, 70.4, 70.5,
70.6, 127.8, 129.7; LRMS (APCI) m/z 437 (M + H+); HRMS
(EI) m/z 459.1653 (M + Na+), calcd for C19H32O9NaS 459.1665.
C
C
24H40O9Na 495.2570; 539.2809 [100, M + Na+], calcd for
26H44O10Na 539.2832.
The distilled water from the aqueous workup was combined
and concentrated under reduced pressure to give a white
precipitate suspended in oil. The suspension was stirred with
diethyl ether (200 mL) overnight and the filtrate concentrated
under reduced pressure to give recovered hexa(ethylene glycol)
ether as a colorless oil (31.85 g, 83%). Spectroscopic analysis
of this material was identical to that of the starting material,
and thus the recovered material was used in subsequent
reactions without further purification.
P olym er 9: St yr en e, 2% Cr oss-Lin k ed w it h r,ω-Bis-
styr yl-p en ta (eth ylen e glycol) 4. Styrene (920 µL, 7.9 mmol),
R,ω-bis-styryl-penta(ethylene glycol) 4 (71.3 mg, 0.161 mmol),
and AIBN (10.5 mg, 0.064 mmol) were combined according to
GP1 to give polymer 9, after washing, as a white beaded
product (223 mg, 25%): IR (KBr disk) νmax 3058, 3024, 2920,
2845, 1601, 1508 cm-1
.
P olym er 10: Styr en e, 14% Cr oss-Lin k ed w ith r,ω-Bis-
styr yl-p en ta (eth ylen e glycol) 4. Styrene (810 µL, 6.9 mmol),
R,ω-bis-styryl-penta(ethylene glycol) 4 (500 mg, 1.13 mmol),
and AIBN (10.5 mg, 0.064 mmol) were combined according to
GP1 to give polymer 10, after washing, as a white beaded
product (985 mg, 80%): IR (KBr disk) νmax 3051, 3016, 2924,
P oly(oxyeth ylen e glycol)400 Mon o-p-tolu en esu lfon a te
(6). According to the procedure described for tri(ethylene
glycol) di-p-toluenesulfonate 1, a solution of TsCl (6.809 g,
0.035 mol) in CH2Cl2 (60 mL) was added to a solution of poly-
(oxyethylene glycol)400 (50.0 mL, 0.14 mol), triethylamine (19.3
mL, 0.14 mol), and DMAP (0.216 g, 1.75 mmol) in CH2Cl2 (250
mL) to give poly(oxyethylene glycol)400 mono-p-toluenesulfonate
6 as a pale yellow oil (18.794 g, 88%), which was used in
subsequent reactions without further purification: IR (thin
2856, 1601, 1510 cm-1
.
P olym er 11: Styr en e, 20% Cr oss-Lin k ed w ith r,ω-Bis-
styr yl-p en ta (eth ylen e glycol) 4. Styrene (750 µL, 6.4 mmol),
R,ω-bis-styryl-penta(ethylene glycol) 4 (724 mg, 1.638 mmol),
and AIBN (10.5 mg, 0.064 mmol) were combined according to
GP1 to give polymer 11, after washing, as a white beaded
product (1.0 g, 71%): IR (KBr disk) νmax 3051, 3025, 2919,
1
film) νmax 3475, 2873, 1597, 1453, 1353, 1177, 1098 cm-1; H
NMR (300 MHz, CDCl3) δH 2.35 (3H, s), 2.48-3.60 (35H, m),
4.06 (2H, t, J ) 4.9), 5.22 (1H, s), 7.25 (2H, d, J ) 7.7), 7.69
(2H, d, J ) 8.2); 13C NMR (75 MHz, CDCl3, PENDANT) δC
21.4, 61.4, 68.4, 69.0, 70.1, 70.3, 70.4, 72.3, 127.7, 129.6, 132.7,
144.6; LRMS (APCI) m/z 613 (100%, [M + H]+), 657 (90%, [M
+ C2H4O + H]+), 569 (82%, [M + H - C2H4O]+), 701 (69%, [M
+ 2(C2H4O) + H]+), 525 (57%, [M + H - 2(C2H4O)]+), 745 (43%,
[M + H + 3(C2H4O)]+), 481 (27%, [M + H - 3(C2H4O)]+).
2856, 1609, 1508 cm-1
.
P olym er 12: Styr en e, 2% Cr oss-Lin k ed w ith r,ω-Bis-
styr yl-tr i(eth ylen e glycol) 3. Styrene (226 µL, 1.95 mmol),
R,ω-bis-styryl-tri(ethylene glycol) 3 (14.1 mg, 0.04 mmol), and
AIBN (13 mg, 0.08 mmol) were combined according to GP1 to
give polymer 12, after washing, as a white beaded product (195
mg, 89%): IR (KBr disk) νmax 3051, 3025, 2927, 2856, 1510
According to the procedure described for hexa(ethylene
glycol) mono-p-toluenesulfonate 5, unreacted poly(oxyethylene
glycol)400 was recovered as a very pale yellow oil (31.5 g, 75%).
Spectroscopic analysis of this material was identical to that
of the starting material, and thus the recovered material was
used in subsequent reactions without further purification.
cm-1
.
P olym er 13: r-St yr yl-h exa (et h ylen e glycol) 7, 2%
Cr oss-Lin k ed w ith Divin yl Ben zen e (DVB). R-Styryl-hexa-
(ethylene glycol) 7 (0.741 g, 1.93 mmol), DVB (0.0064 g, 0.039
mmol), and AIBN (2.5 mg, 0.015 mmol) were combined
according to GP2 to give, after washing, polymer 13 as an
opaque white gel (0.566 g, 76%): IR (gel compressed between
NaCl disks) νmax 3439, 3025, 2920, 2847, 1610, 1506, 1451
r-Styr yl-h exa (eth ylen e glycol) (7). According to the
procedure described for R,ω-bis-styryl-tri(ethylene glycol) 3,
4-acetoxystyrene (0.50 mL, 3.14 mmol) was reacted with an
ethanolic solution of potassium hydroxide (0.828 g, 12.55
mmol) at room temperature and then under reflux. An
ethanolic solution of hexa(ethylene glycol) mono-p-toluene-
sulfonate 5 (1.728 g, 3.14 mmol) was added to the refluxing
reaction mixture to give R-styryl-hexa(ethylene glycol) 7, after
flash column chromatography (5% v/v EtOH in CH2Cl2), as a
pale yellow oil (0.651 g, 54%): IR (thin film) νmax 3443, 2872,
cm-1
.
P olym er 14: r-Styr yl-p oly(oxyeth ylen e glycol)400 8, 2%
Cr oss-Lin k ed w ith DVB. R-Styryl-poly(oxyethylene glycol)400
8 (0.3011 g, 0.564 mmol), DVB (0.0021 g, 0.013 mmol), and
AIBN (0.6 mg, 0.004 mmol) were combined according to GP2
to give, after washing, polymer 14 as a clear gel (0.155 g,
51%): IR (gel compressed between NaCl disks) νmax 3370, 3076,
3033, 2909, 2867, 1608, 1109 cm-1
.
1
1606, 1510, 1454, 1114 cm-1; H NMR (300 MHz, CDCl3) δH
P olym er 15: r-St yr yl-h exa (et h ylen e glycol) 7, 2%
Cr oss-Lin k ed w ith r,ω-Bis-styr yl-p en ta (eth ylen e glycol)
4. R-Styryl-hexa(ethylene glycol) 7 (0.50 g, 1.3 mmol), R,ω-bis-
styryl-penta(ethylene glycol) 4 (0.0117 g, 0.027 mmol), and
AIBN (1.7 mg, 0.010 mmol) were combined according to GP2
to give, after washing, polymer 15 as a clear gel (0.210 g,
41%): IR (gel compressed between NaCl disks) νmax 3414, 3025,
3.37-3.53 (20H, m), 3.64 (2H, t, J ) 4.6), 3.92 (2H, t, J ) 4.6),
4.93 (2H, d, J ) 10.9), 5.42 (1H, d, J ) 17.6), 6.48 (1H, dd, J
) 10.9, 17.5), 6.69 (2H, d, J ) 8.8), 7.14 (2H, d, J ) 8.8); 13C
NMR (75 MHz, CDCl3, PENDANT) δC 60.1, 62.3, 66.2, 68.4,
69.0, 69.3, 69.5, 71.5, 110.3, 113.4, 126.2, 129.2, 135.1, 157.5;
LRMS (APCI) m/z 385 (M + H+); HRMS (EI) m/z 407.2050 (M
+ Na+), calcd for C20H32O7Na 407.2046.
2954, 2918, 2847, 1607, 1501, 1451, 1067 cm-1
.
r-Styr yl-p oly(oxyeth ylen e glycol)400 (8). According to the
procedure described for R,ω-bis-styryl-tri(ethylene glycol) 3,
4-acetoxystyrene (0.87 mL, 5.4 mmol) was reacted with an
ethanolic solution of potassium hydroxide (0.677 g, 10.8 mmol)
at room temperature and then under reflux. An ethanolic
solution of poly(oxyethylene glycol)400 mono-p-toluenesulfonate
6 (3.323 g, 5.43 mmol) was added to the refluxing reaction
mixture to give R-styryl-poly(oxyethylene glycol)400 8, after
flash column chromatography (5% v/v EtOH in CH2Cl2), as a
pale yellow oil (0.803 g, 29%): IR (thin film) νmax 3477, 3087,
3042, 2872, 1607, 1454, 1110 cm-1; 1H NMR (300 MHz, CDCl3)
δH 3.38-3.52 (32H, m), 3.65 (2H, t, J ) 4.8), 3.93 (2H, t, J )
5.1), 4.93 (1H, d, J ) 10.8), 5.42 (1H, d, J ) 17.7), 6.46 (1H,
P olym er 16: r-Styr yl-p oly(oxyeth ylen e glycol)400 8, 2%
Cr oss-Lin k ed w ith r,ω-Bis-styr yl-p en ta (eth ylen e glycol)
4. R-Styryl-poly(oxyethylene glycol)400 8 (0.3308 g, 0.640 mmol),
R,ω-bis-styryl-penta(ethylene glycol) 4 (0.0058 g, 0.013 mmol),
and AIBN (0.8 mg, 0.005 mmol) were combined according to
GP2 to give, after washing, polymer 15 as a clear gel (0.168 g,
50%): IR (gel compressed between NaCl disks) νmax 3416, 3025,
2920, 2847, 1611, 1506, 1452, 1098, 1069, 1040 cm-1
.
Ack n ow led gm en t. We thank Aston University for
financial support. We thank Dr. Mike Perry and Mrs.
Karen Farrow (both of Aston University) for NMR and
LRMS, respectively, and Mr. Peter Ashton (School of
4854 J . Org. Chem., Vol. 67, No. 14, 2002

Poly(Oxyethylene Glycol) Polymer (POP) Supports
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for all new compounds. This material is available free
of charge via the Internet at http://pubs.acs.org.
Chemistry, Birmingham University) for HRMS. We
thank Mr. David Bleby (Aston University) for compiling
the software used in the operation of the microbalance.
We thank Dr. Anna V. Hine (Aston University) and Ms.
Lisa Touw for critical reviews of this manuscript.
J O020071B
J . Org. Chem, Vol. 67, No. 14, 2002 4855