Reaction of glycidyl methacrylate at the hydroxyl and carboxylic groups of poly(vinyl alcohol) and poly(acrylic acid): Is this reaction mechanism still unclear?

Article abstract of DOI:10.1021/jo900033c

(Chemical Equation Presented) Transesterification and epoxide ring-opening reactions are two mechanism routes that explain chemical modifications of macromolecules by glycidyl methacrylate (GMA). Although the coupling reaction of the GMA with macromolecul

Full text of DOI:10.1021/jo900033c

Reaction of Glycidyl Methacrylate at the Hydroxyl and Carboxylic
Groups of Poly(vinyl alcohol) and Poly(acrylic acid): Is This
Reaction Mechanism Still Unclear?
Adriano V. Reis,† Andre´ R. Fajardo,† Ivania T. A. Schuquel,† Marcos R. Guilherme,‡
Gentil Jose´ Vidotti,† Adley F. Rubira,† and Edvani C. Muniz*,†
Grupo de Materiais Polime´ricos e Compo´sitos, Departamento de Qu´ımica, UniVersidade Estadual de
Maringa´ (UEM), 87020-900, Maringa´, PR, Brazil, and Faculdade de Engenharia Qu´ımica,
Departamento de Sistemas Qu´ımicos e Informa´tica DESQ, Zeferino Vaz, UniVersidade Estadual de
Campinas, 13081-970, Campinas, SP, Brazil
ecmuniz@uem.br
ReceiVed January 14, 2009
Transesterification and epoxide ring-opening reactions are two mechanism routes that explain chemical
modifications of macromolecules by glycidyl methacrylate (GMA). Although the coupling reaction of
the GMA with macromolecules has widely been investigated, there are still mechanisms that remain to
be explained when GMA is processed in an aqueous solution at different pH conditions. To this end,
reaction mechanisms of poly(vinyl alcohol) (PVA) and poly(acrylic acid) (PAAc) by GMA in water in
acidic and basic conditions were investigated thoroughly. The presence of hydroxyl groups in PVA and
carboxyl groups in PAAc allowed for a better evaluation of the reaction mechanisms. The analysis of the
1H and 13C NMR spectra clearly demonstrated that the chemical reactions of GMA with carboxyl groups
and alcohols of the macromolecules in an aqueous solution are dependent on pH conditions. At pH 3.5,
the GMA reacts with both the carboxylic and the hydroxyl groups through an epoxide ring-opening
mechanism. At pH 10.5, the GMA undergoes a hydrolysis process and reacts with hydroxyl groups by
way of both the transesterification and the epoxide ring-opening mechanisms, whereas the ring-opening
reaction is the preferential pathway.
Introduction
from the GMA onto the structure of the macromolecule, which
enables it to undergo a gelling process through a radical cross-
linking polymerization reaction.1-7 The synthesis of hydrogels
from chemically modified polymers is a motivating way for
developing biodegradable polymer networks, which are strongly
Although natural and synthetic polymers are reactive toward
many cross-linking agents, such as di-n-methyol compounds,
divinyl sulfones, and diepoxides, the chemical reaction of
polymers with the use of glycidyl methacrylate (GMA) as a
modifier has been a suitable strategy for producing vinyl
macromolecules. From a chemical point of view, this methodol-
ogy consists of incorporating carbon-carbon π-bonds coming
(1) van Dijk-Wolthuis, W. N. E.; Kettenes-van den Bosch, J. J.; van der
Kerk-van Hoof, A.; Hennink, W. E. Macromolecules 1997, 30, 3411–3413.
(2) van Dijk-Wolthuis, W. N. E.; Franssen, O.; Talsma, H. M. J.; van
Steenbergen, J. J.; den Bosch, K.-V.; Hennink, W. E. Macromolecules 1995,
28, 6317–6322.
(3) Sutter, M.; Siepmann, J.; Hennink, W. E.; Jiskoot, W. J. Controlled
Release 2007, 119, 301–312.
† Universidade Estadual de Maringa´.
‡ Universidade Estadual de Campinas.
3750 J. Org. Chem. 2009, 74, 3750–3757
10.1021/jo900033c CCC: $40.75 2009 American Chemical Society
Published on Web 04/10/2009

GMA Reaction Mechanism
GMA in an aprotic solvent. Li et al.19 discussed the reaction
mechanisms between the chondroitin sulfate and the GMA in a
protic solvent at pH 7.6. Both of the reaction mechanisms may
take place simultaneously, depending on pH and the chemical
nature of the solvent. It has been also described that the
transesterification mechanism is a rapid and reversible reaction
route and that the epoxide ring-opening mechanism is a slow
and irreversible reaction route. Over the initial stage of the
reaction, there is a predominant formation of the resultant
products of the transesterification. With the evolution of the
reaction, there is a decrease in pH of the reaction medium that
limits the transesterification and makes the epoxide ring-opening
mechanism more favorable. By this logic, for a long period of
reaction, the formation of the resultant products of the epoxide
ring-opening mechanism would be predominant over that of the
transesterification mechanism. However, the reaction of chon-
droitin sulfate by GMA at pH 3 indeed occurs via epoxide ring
opening.13 In this case, there is an attachment of a whole GMA
molecule onto the sulfate and carboxylic groups of the chon-
droitin sulfate. When the reaction is processed via transesteri-
fication, only hydroxyl groups of the polysaccharide are directly
attached to the methacryloyl groups from the GMA. Although
the reaction mechanism of the GMA with chondroitin sulfate
in an aqueous medium has been described, there is still an
interesting question that remains to be answered: could the
hydroxyl groups of the chondroitin sulfate also react with the
GMA by way of an epoxide ring-opening route in a protic
solvent? With the purpose of responding to this question and
also complementing the studies performed by both van Dijk-
Wolthuis et al.1 and Li et al.,19 a detailed examination of the
reaction mechanisms of poly(vinyl alcohol) (PVA) and poly-
(acrylic acid) (PAAc) by GMA in water was performed. The
idea of using these polymers as model compounds may be based
on their chemical structures: the presence of the hydroxyl groups
of PVA and the carboxyl groups of PAAc allowed for a better
evaluation of the reaction mechanisms. The use of polymers
with different functional groups enabled us to better understand
and describe the resultant products and mechanisms of reactions
by GMA. Functionalization of macromolecules by way of either
the ring opening of epoxides20 or transesterification21 is an
important issue on laboratorial and industrial scales. There have
been no reports describing a thorough investigation on the
reaction mechanisms of GMA with macromolecules in water.
This work aims to be a contribution for a better comprehension
of the reaction mechanisms of macromolecules by GMA.
FIGURE 1. Schema of the chemical reaction of GMA with a
macromolecule by way of transesterification and epoxide ring-opening
mechanisms.
recommended for uses in the development of new modified
drug-delivery devices and vitro-retinal replacement surgery.8-14
Furthermore, superabsorbent hydrogels for applications in which
the efficient use of water is required, for example, soil con-
ditioning in agriculture, can be synthesized through a polym-
erization cross-linking reaction at the vinyl moiety of the
modified polymer with acrylic monomers.5
There are two reaction routes that explain chemical modifica-
tions of natural and synthetic polymers through the use of the
GMA: transesterification and epoxide ring-opening mech-
anisms.14-18 The reaction mechanism of GMA with dextran
(Dex), by using dimethyl sulfoxide (DMSO) as a solvent and
4-(N,N-dimethylamino)pyridine (DMAP) as a catalytic agent,
has been reported by van Dijk-Wolthuis et al.1,2 It has been
found that transesterification is the predominant route for the
GMA-Dex system when a polar aprotic solvent, such as the
DMSO, is used as a reaction medium. Methacrylated Dex was
found as a main product and glycidol (GDOL) as a byproduct.
Equivalent results were verified when inulin was treated with
(4) Vervoort, L.; Van Der Mooter, G.; Augustijns, P.; Busson, R.; Toppet,
R.; Kinget, R. Pharm. Res. 1997, 14, 1730–1737.
(5) Guilherme, M. R.; Reis, A. V.; Takahashi, S. H.; Rubira, A. F.; Feitosa,
J. P. A.; Muniz, E. C. Carbohydr. Polym. 2005, 61, 464–471.
(6) Reis, A. V.; Cavalcanti, O. A.; Rubira, A. F.; Muniz, E. C. Int. J. Pharm.
2003, 267, 13–25.
Results and Discussion
(7) Reis, A. V.; Guilherme, M. R.; Rubira, A. F.; Muniz, E. C. Polymer
2006, 47, 2023–2029.
Spectroscopic Characterization of GMA and Modified
Polymers in pH 3.5 and pH 10.5. GMA Molecule. For a better
evaluation of the GMA reaction with the polymers, a more
detailed schema of both the transesterification and the epoxide
ring-opening mechanisms is shown in Figure 1. The reaction
products that result in an epoxide ring opening pathway are two
isomers: 3-methacryloyl-1-glyceryl and 3-methacryloyl-2-glyc-
eryl esters. Methacrylated polymer, as the main product, and
GDOL as the byproduct are the results of a transesterification
(8) Vervoort, L.; Rombout, P.; Van Der Mooter, G.; Augustijns, P.; Kinget,
R. Int. J. Pharm. 1998, 172, 137–145.
(9) Rubinstein, A. Drug DeV. Res. 2000, 50, 435–439.
(10) Chen, L. G.; Liu, Z. L.; Zhuo, R. X. Polymer 2005, 6, 6274–6281.
(11) Basan, H.; Gumusderelioglu, M.; Orbey, M. T. Eur. J. Pharm. Biopharm.
2007, 65, 39–46.
(12) Gliko-Kabir, I.; Yagen, B.; Baluom, M.; Rubinstein, A. J. Controlled
Release 2000, 63, 129–134.
(13) Reis, A. V.; Guilherme, M. R.; Mattoso, L. H. C.; Rubira, A. F.;
Tambougi, E. B.; Muniz, E. C. Pharm. Res. 2009, 26, 438–444.
(14) Tortora, M.; Cavalieri, F.; Chiessi, E.; Paradossi, G. Biomacromolecules
2007, 8, 209–214.
1
(15) Ferreira, L.; Vidal, M. M.; Geraldes, C. F. G. C.; Gil, M. H. Carbohydr.
Polym. 2000, 41, 15–24.
(16) Hennink, W. E.; Franssen, O.; van Dijk-Wolthuis, W. N. E.; Talsma,
H. J. Controlled Release 1997, 48, 107–114.
pathway. Figure 2a,b shows the H and 13C NMR reference
spectra of GMA. The resonance lines in both of the NMR
(17) Crispim, E. G.; Piai, J. F.; Rubira, A. F.; Muniz, E. C. Polym. Test.
2006, 25, 377–383.
(18) Ferreira, L.; Vidal, M. M.; Geraldes, C. F. G. C.; Gil, M. H. Carbohydr.
Polym 2000, 41, 15–24.
(19) Li, Q.; Wang, D.; Elisseeff, J. H. Macromolecules 2003, 36, 2556–
2562.
(20) Holbach, M.; Weck, M. J. Org. Chem. 2006, 71, 1825–1836.
(21) Co´rdova, A.; Janda, K. D. J. Org. Chem. 2001, 66, 1906–1909.
J. Org. Chem. Vol. 74, No. 10, 2009 3751

Reis et al.
FIGURE 2. 1H (a) and 13C (b) NMR spectra of the pure GMA (DMSO-d6).
87.5% as the 3-methacryloyl-2-glyceryl ester, in a reaction
medium at pH 3.5.
13C NMR spectra of PAAc and PAAc-MA-3.5, shown in
Figure 5, were also recorded to confirm the 1H NMR data. The
corresponding signals of the vinyl carbon were clearly observed
at δ 138.77 and δ 129.86 in the PAAc-MA-3.5 spectrum,
methyl carbon at δ 23.43, and carbonyl carbon at δ 172.40.
The signal in the spectral region of δ 80-60 reveals the presence
of the glyceryl spacer. In addition, the corresponding signals
of the four- and five-numbered carbons in the inset were detected
at δ 78.68 (4) for the 3-methacryloyl-1-glyceryl ester of PAAc
and at 72.66 (5) for the 3-methacryloyl-2-glyceryl ester of PAAc.
Both the 1H and the 13C NMR data demonstrated that the acidic
reaction in which the GMA molecule is attached onto the PAAc
structure occurs by way of an epoxide ring-opening mechanism.
The proportion of the ring-opening products consisted of 12.5%
as the 3-methacryloyl-1-glyceryl ester of PAAc and 87.5% as
the 3-methacryloyl-2-glyceryl ester of PAAc.
FIGURE 3. 1H NMR spectra of PAAc and PAAc-MA-3.5 for a
coupling reaction at pH 3.5 (300 MHz, D2O).
A drawing of coupling reactions of GMA with PAAc in an
aqueous solution at pH 3.5 is shown in Figure 6. The whole
process starts off with the transfer of a proton from an acidic
liquid onto the epoxide-linked hydroxyl group of the GMA
molecule (p-GMA). When the p-GMA reacts with PAAc, the
epoxide ring-opening reaction of the GMA should occur through
two mechanism pathways, yielding two isomers as the reaction
product: the 3-methacryloyl-1-glyceryl ester of PAAc (pathway
1) and the 3-methacryloyl-2-glyceryl ester of PAAc (pathway
2).
spectra were indentified and associated with the corresponding
1H and 13C nuclei at the GMA molecule, drawn in the inset.
1
PAAc-MA-3.5. Figure 3 shows H NMR spectra of PAAc
and PAAc-MA-3.5. The signals at δ 6.17 and δ 5.74, in the
PAAc-MA-3.5 spectrum, were assigned to vinyl carbon-linked
hydrogen. The signal at δ 1.94 corresponded to methyl carbon-
linked hydrogen at the vinyl carbons, and the signals at δ 5.06
and δ 4.02 were attributed to a glyceryl spacer coming from
GMA. The appearance of these signals indicates the formation
of the 3-methacryloyl-1-glyceryl ester of PAAc and the 3-meth-
acryloyl-2-glyceryl ester of PAAc, which are reaction products
resultant of the epoxide ring-opening mechanism pathway. In
the view that two products can be formed by way of an epoxide
ring-opening reaction, a more detailed examination in the
spectral region of δ 5-3 was carried out to determine the
proportion of the methacryloyl-1-glyceryl ester and methacry-
loyl-2-glyceryl ester products.
1
PAAc-MA-10.5. Neither H NMR nor 13C NMR spectra
demonstrated any evidence for the reaction of GMA with PAAc
in an aqueous solution at pH 10.5 (spectra not shown here),
compared with the corresponding reference spectra of GMA
and PAAc. The lack of spectroscopic evidence for the reaction
products of GMA with PAAc was very likely caused by the
basic conditions of the reaction medium.
According to the literature,18 the GMA undergoes a hydrolysis
reaction at the basified media, yielding deprotonated methacrylic
acid (up-AcMet) and GDOL, which can also acquire a depro-
tonated form at the strongly basic conditions, as shown in Figure
7. The deprotonation of the GDOL occurs because the negative
charge that exists on the molecule is stabilized by a resonance
mechanism that delocalizes the charge over both oxygen atoms.
With the increasing pH of the medium, the reaction equilibrium
is delocalized towards nucleophiles, such as dp-AcMet, dp-
1
Figure 4 shows expanded H NMR spectra of PAAc and
PAAc-MA-3.5 in the spectral region of δ 5-3. The signals at
δ 5.06 and δ 4.02 were attributed to the hydrogen of the
methacryloyl-1-glyceryl and methacryloyl-2-glyceryl esters,
respectively, as indicated in the spectrum. The ratio of the
integrals of these two signals corresponded to 1:8. This means
that approximately 12.5% of the GMA were attached to the
PAAc structure as the 3-methacryloyl-1-glyceryl ester and
3752 J. Org. Chem. Vol. 74, No. 10, 2009

GMA Reaction Mechanism
FIGURE 4. Expanded 1H NMR spectra of PAAc and PAAc-MA-3.5 in the spectral region of δ 5-3, for a coupling reaction at pH 3.5 (300 MHz,
D2O).
FIGURE 5. 13C NMR spectra of PAAc and PAAc-MA-3.5 for a coupling reaction at pH 3.5 (75.5 MHz, D2O).
GDOL, and dp-PAAc, and this appears to be an unsuitable
condition for reaction processing.
conditions, the GMA molecule recovers to its original structure,
and thereby, the reaction indeed occurs by way of an epoxide
ring-opening mechanism.
Reactions of GMA with chondroitin sulfate at slightly basic
conditions (pH 8.5) have already been investigated.18 It has been
reported that the GDOL couples onto both the carboxylate
PVA-MA-3.5. Figure 8 shows 1H NMR spectra of PVA and
PVA-MA-3.5. The signals observed in the PVA-MA-3.5
spectrum, which evidence the resultant product of the GMA-
PVA reaction at pH 3.5, were associated with their correspond-
ing 1H as follows: vinyl carbon-linked hydrogen at δ 6.21 and
5.74 and methyl carbon-linked hydrogen at the vinyl carbon at
δ 1.98. The corresponding signal of the glyceryl spacer was
observed in the spectral region of δ 4.5-3.5. This means that
the coupling reaction of GMA onto PVA is processed through
an epoxide ring-opening pathway. In view of the overlap at the
spectral region of δ 4.5-3.5, the proportion of the isomers, the
(-COO-) and the sulfate (-SO3 ) groups of chondroitin sulfate.
-
As discussed in the prior part of this paper, the coupling reaction
of GMA with the carboxylate groups at PAAc was not verified.
There may be a dependence of the reaction conditions on pH.
With changing pH, there should be a variation of concentration
of protonated and deprotonated molecules that hinders the
coupling reaction of the GMA with the polymer. By considering
that the reaction kinetics is dependent on the concentration of
the molecules, the pH would then have a significant effect on
the coupling velocity of the molecules onto PAAc. At low pH
J. Org. Chem. Vol. 74, No. 10, 2009 3753

Reis et al.
FIGURE 6. Schema of the coupling reaction of GMA with PAAc in
an aqueous solution at pH 3.5 via an epoxide ring-opening mechanism.
3-methacryloyl-1-glyceryl ether of PVA and the 3-methacryloyl-
2-glyceryl ether of PVA, cannot be determined.
Figure 9 shows the 13C NMR spectra of PVA and PVA-MA-
3.5. The corresponding 13C-resonance signals of the vinyl carbon
in the PVA-MA-3.5 spectrum were observed at δ 138.4 and δ
130.21, carbonyl carbon at δ 178.00, and methyl carbons at δ
20.08. The corresponding 13C chemical shifts of the glyceryl
spacer, amplified and shown in the inset, were observed in the
spectral region of δ 80-60. The signals observed at δ 77.33
and 72.43 were attributed respectively to the carbon resonances
of the 3-methacryloyl-1-glyceryl ether of PVA (carbon 4) and
of the 3-methacryloyl-2-glyceryl ether (carbon 5) of PVA-MA-
FIGURE 7. Schema of a hydrolysis reaction of GMA and the ionization
of PAAc. With the increasing pH of the medium, the reaction
equilibrium is delocalized toward three nucleophiles, such as dp-AcMet,
dp-GDOL, and dp-PAAc.
1
3.5. The 13C NMR data, which corroborate the H NMR data,
demonstrate that GMA reacts with alcohol groups at the PVA
structure at pH 3.5 through an epoxide ring-opening mechanism.
In response to the question proposed in the introductory part
of this paper, it can be said that the GMA indeed reacts with
the hydroxyl groups of the macromolecules in an aqueous
solution at pH 3.5 through an epoxide ring-opening mechanism.
A proposed schema of such a reaction is shown in Figure 10.
In an acidified aqueous medium, the p-GMA reacts with the
PVA through an epoxide ring-opening mechanism, thus yielding
the two isomers: the 3-methacryloyl-1-glyceryl ether of PVA
and the 3-methacryloyl-2-glyceryl ether of PVA.
FIGURE 8. 1H NMR spectra of PVA and PVA-MA-3.5 for a coupling
PVA-MA-10.5. Figure 11 shows 1H NMR spectra of PVA
and PVA-MA-0.5. The appearance of the signals at δ 6.18
and δ 5.74 in the PVA-MA-10.5 spectrum was attributed to
the vinyl carbon-linked hydrogen, and the signal at δ 1.94 was
associated with the carbon methyl-linked hydrogen at the vinyl
carbon. The corresponding 1H signal of the glyceryl spacer was
observed at the spectral region of δ 4.5-3.5, as evidence of
the occurrence of the epoxide ring-opening reaction.
reaction at pH 3.5 (300 MHz, D2O).
because of the overlap of signals at the region of δ 4.5-3.5.
The appearance of three new signals at δ 5.67, 5.36 (vinyl
carbon-linked hydrogen), and 1.86 (methyl carbon-linked
hydrogen at the vinyl groups) is most likely caused by the
formation of transesterification products: vinyl methacrylate of
PVA-MA-10.5 and GDOL. The proportion of the reaction
products of transesterification and epoxide ring-opening were
calculated by the ratio between the area of the signals at δ 5.67
The proportion of 3-methacryloyl-1-glyceryl ether and 3-meth-
acryloyl-2-glyceryl ether of PVA-MA-10.5 was not determined
3754 J. Org. Chem. Vol. 74, No. 10, 2009

GMA Reaction Mechanism
FIGURE 9. 13C NMR spectra of PVA and PVA-MA-3.5 for a coupling reaction at pH 3.5 (75.5 MHz, D2O).
transesterification reaction and 85.7% via the epoxide ring-
opening reaction.
Figure 12 shows 13C NMR spectra of PVA and PVA-MA-
10.5. The corresponding 13C signals of the carbons at the
3-methacryloyl-1-glyceryl ether (carbon 6) and 3-methacryloyl-
2-glyceryl ether (carbon 7), both of PVA-MA-10.5, were
observed at δ 77.35 and at δ 72.24, respectively. These signals
are additional evidence of the epoxide ring-opening reaction.
Nevertheless, the signal at δ 18.51, corresponding to methyl
carbon at the PVA-MA-10.5, indicated the occurrence of the
1
transesterification reaction. From the H and 13C NMR data, it
would then be concluded that the coupling reaction of GMA
with PVA at pH 10.5 occurred through both the transesterifi-
cation and the epoxide ring-opening pathways, with an integral
ratio of 1:7.
Figure 13 shows a proposed schema of coupling mechanism
routes of GMA with PVA. In an aqueous solution with pH 10.5,
a given number of hydroxyl groups from the PVA are converted
to a deprotonated form that generates ethoxide molecules. It
follows that the ethoxides could react with the GMA through
three mechanism routes: (1) with the epoxide ring at GMA
resulting in the 3-methacryloyl-1-glyceryl ether of PVA, (2) with
GMA in the same way of route 1 but resulting in the
3-methacryloyl-1-glyceryl ether of PVA, and (3) with carbonyl
groups at GMA resulting in both vinyl methacrylate of PVA
and GDOL, as products.
FIGURE 10. Schema of the coupling reaction with PVA in an aqueous
solution at pH 3.5. The p-GMA reacts with hydroxyl groups of PVA
through an epoxide ring-opening mechanism, yielding two isomers:
the 3-methacryloyl-1-glyceryl ether of PVA and the 3-methacryloyl-
2-glyceryl ether of PVA.
Conclusion
The chemical reactions of the GMA with acid groups
(-COOH) and alcohols (-OH) of the macromolecules in an
aqueous solution are dependent on pH conditions. At pH 3.5,
the GMA reacts with both the carboxylic and the hydroxyl
groups through an epoxide ring-opening mechanism. At pH 10.5,
the GMA undergoes a hydrolysis process and reacts with
and δ 5.36 and the area of the signals at δ 6.18 and δ 5.74,
respectively.
With a ratio of [transesterification product]/[epoxide ring -
opening product] of 1/7, the total amount of attached GMA in
the PVA at pH 10.5 was obtained as follows: 14.3% via the
J. Org. Chem. Vol. 74, No. 10, 2009 3755

Reis et al.
FIGURE 11. 1H NMR spectra of PVA and PVA-MA-10.5 for a coupling reaction at pH 10.5 (300 MHz, D2O).
FIGURE 12. 13C NMR spectra of PVA and PVA-MA-10.5 for a coupling reaction at pH 10.5 (75.5 MHz, D2O).
prepared according to the following methodologies: 1.5 g of
PAAc was dissolved into 150 mL of distilled-deionized water
under a stirring speed of 300 rpm at room temperature. After
the mixture was completely homogenized, 200 µL of a 2 mol
L-1 HCl solution was dropped into the mixture to adjust the pH
to 3.5, and 6 mL of a 2 mol L-1 NaOH solution was used to
obtain pH 10.5. After that, 0.98 mL of GMA was mixed into
either solution by a constant and vigorous stirring at 50 °C for
24 h. Then, 10 mL of acetone were introduced to precipitate
the reaction product, which was separated by a centrifugation
process at room temperature. The as-prepared products were then
hydroxyl groups by way of both the transesterification and the
epoxide ring-opening mechanisms, whereas the ring-opening
reaction is the preferential pathway.
Experimental Section
Materials. Starting reagents were used without further purifica-
tion: GMA PVA >99% hydrolyzed (average Mw 124 000-186 000);
PAAc (99% average Mw 750 000); sodium hydroxide (NaOH, 95%);
chloridric acid (HCl, 36.5-38%); acetone (99.5%).
Chemical Modification of PAAc by GMA (PAAc-MA).
PAAc-modifying solutions of either pH 3.5 or pH 10.5 were
1
lyophilized to record H and 13C NMR spectra.
3756 J. Org. Chem. Vol. 74, No. 10, 2009

GMA Reaction Mechanism
FIGURE 13. Schema of the reaction of GMA with PVA in an aqueous solution at pH 10.5 through three mechanism routes.
Chemical Modification of PVA by GMA (PVA-MA). PVA-
modifying solution was prepared by using the analogous methodol-
ogy to that of the PAAc, except for adjusting the pH of the acidic
and basic solutions. Here, 440 µL of 2 mol L-1 HCl solution was
used for pH 3.5 and 520 µL of 2 mol L-1 NaOH solution for pH
10.5. By considering the different pH conditions used to modify
both the polymers, the following labels were used to identify them:
PAAc-MA-3.5 for pH 3.5, PAAc-MA-10.5 for pH 10.5,
PVA-MA-3.5 for pH 3.5, and PVA-MA-10.5 for pH 10.5.
NMR Measurements. NMR spectra were performed on a
Varian Mercury plus BB 300 MHz spectrometer, operating at
1H NMR spectra. For the 13C NMR, a pulse angle of 30° was
used with a relaxation delay of 1 s. DMSO-d6, as the solvent,
and tetramethylsilane (TMS), as the internal standard, were used
for recording the GMA spectra. DEPT, HMQC, and COSY
spectra were also performed for help on the attribution of the
1
chemical shifts of both the H and the 13C.
Acknowledgment. E.C.M. acknowledges the Conselho Na-
cional de Desenvolvimento Tecnolo´gico (CNPq-Brazil) for
financial support, Proc. 308611/2006-3. A.V.R. and A.R.F. thank
the CNPq Brazil for their undergraduate and doctorate fellow-
ships, respectively. M.R.G. is grateful to Fundac¸a˜o de Amparo
a Pesquisa do Estado de Sa˜o Paulo (FAPESP, Proc. 06/50952-
4) for his postdoctoral fellowship.
1
300.059 MHz for H and 75.457 MHz for 13C. D2O solutions
consisting of 150 mg L-1 of polymer (raw or modified one) and
0.05% 3-(trimethylsilyl)propionic-2,2,3,3-d4 acid sodium salt
(TSP-d4), as the internal standard (0 ppm), were prepared in
NMR tubes of 5 mm diameter to acquire the spectra. The angle
pulse of 90° with a relaxation delay of 30 s was used for
JO900033C
J. Org. Chem. Vol. 74, No. 10, 2009 3757