Synthesis of Poly(Methacrylic Acid) using RAFT
Polymerization
Danielle Petko1 and Dr. Devon Shipp2
Department of Chemistry, Clarkson University
Introduction:
Synthetic polymers have been in use in everyday life for over half a century and are becoming
more important by the day. As polymers are beginning to be used in fine biological and medicinal
applications, it has been increasingly important to have control over the lengths, weights, and
functionality of polymer chains. The most important technique developed in order to obtain that control
has been living radical polymerization (LRP). With LRP, this control is achieved simply by controlling
the concentrations of the monomer and initiator of the polymerization in the reaction mixture. The
research presented in this abstract focuses on a type of LRP called reversible addition-fragmentation chain
transfer (RAFT) polymerization.3
The overall goal of this project has been to use RAFT polymerization to produce
poly(methacrylic acid).
What makes the synthesis of this polymer difficult is that attempting to
polymerize methacrylic acid directly often results in by-products and difficult purification and
characterization procedures. The past two months have been spent synthesizing poly(methacrylic acid)
by first polymerizing the “protected” methacrylate monomers tert-butyl methacrylate (t-BMA) and benzyl
methacrylate (BMA), and then removing the DTE end group and also the protecting groups using acid
hydrolysis (for t-BMA). The polymerization of the methacrylate monomers has been aimed at polymers
with weights of approximately 5,000, which is relatively small in the world of macromolecules. Using
polymers of this weight makes the analysis of the polymer in later steps of the synthesis of
poly(methacrylic acid) easier, as it will be easier to see whether or not the end groups have been removed.
In the past, poly(2-ethacrylic acid), which
is structurally similar to poly(methacrylic acid), has
been used to produce phosphatidylcholine vesicles
by attaching a bioconjugate end group to the
polymer. These vesicles are sensitive to changes in
pH, releasing their contents upon the increased
acidity of their environment. This property allows
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the vesicles to be used for drug delivery.4 The synthesis of poly(methacrylic acid) will hopefully lead to
the attachment of a bioconjugate end group to the polymer so that it can be used for similar applications.
Methods:
All of the polymerization reactions were performed using the same basic procedures using 2-(2Cyanopropyl) Dithiobenzoate (CPDB) as the RAFT mediating agent, 2,2'-azobisisobutytonitrile (AIBN)
as the initiator, and anisole as a solvent. The reactions were performed in all glass Schlenck flasks, using
a series of three freeze-pump-thaws to remove any oxygen present before heating in an oil bath at 60°C.
Nitrogen was used to prevent oxygen from getting into the flask when samples were being removed to
examine the kinetics of the reactions. A series of reactions with various molar ratios were attempted
using both monomers in order to find the best method for synthesizing a polymer having a low
polydispersity and molecular weight of 5,000.
The reaction conditions of the most successful
polymerization of tert-butyl methacrylate (DP05) and of benzyl methacrylate (DP10) are given in Table
1. Polymers were then dissolved in THF and precipitated into methanol/water (DP05) or hexanes (DP10).
Table 1. Reaction conditions for RAFT polymerization of t-BMA and BMA (mole ratios unless
otherwise indicated).
Monomer
CPDB
AIBN
Anisole
Time (hrs)
(vol., ml)
Mn
Mw/Mn
(g/mol.)
DP05
40
a
1
0.05
5
21
5,100
1.18
DP10
50 b
1
0.1
2.25
3
4,300
1.20
a
Volume of t-BMA used = 5 ml.
b
Volume of BMA used = 4.5 ml.
The removal of the dithiobenzoate end group from both polymers was performed using ethylene
diamine. For poly(t-BMA), 0.2 g of the product from DP05 was heated in a Schlenck flask with 20 µL of
ethylene diamine and 10 mL of chloroform for 24 hours at 40°C. The mixture was then rotovapped down
to remove the chloroform and dried. After 48 hours, the polymer was at the bottom of the vial with a
viscous liquid resembling ethylene glycol on top of it. This liquid was decanted off, and the polymer was
washed with methanol before being placed into the vacuum oven for drying. For poly(BMA), 0.2010 g of
the product from DP10 was heated in a Schlenck flask with 10 mL of chloroform, and 20 µL of ethylene
diamine for 24 hours at 40°C. The mixture was rotovapped down to remove the chloroform and then
precipitated into hexanes and dried in the vacuum oven.
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Acid hydrolysis was also performed on the poly(t-BMA) product from DP05 in an attempt to
remove the t-butyl protecting group. 0.25 g poly(t-BMA) from DP05 was refluxed for 24 hours with 2.5
mL of 1,4-dioxane and 0.5 mL of 10% HCl. 5 Most of the solvent was removed using rotary evaporation
before precipitation into diethyl ether.
Results and Discussion:
Synthesis of the polymers was very successful, as the desired weights and polydispersities were
obtained. Scheme 1 shows the overall polymerization and resulting polymers. The polydispersities for
both reactions were close to 1.0, which is very good. The poly(t-BMA) had an overall conversion of
monomer to polymer of 31%, and the poly(BMA) had an overall conversion of monomer to polymer of
approximately 14%. These conversions are relatively low, but that is due to the small size of the
polymers synthesized.
Scheme1. Overall Polymerization of t-BMA and BMA
O
S
S
O
CN
S
+
O
OR
CH3
CH3
AIBN, 60°C
S
Anisole
C
CH2
n
C
O
O
C
CH3
CN
O
R
CH3
where R =
C
DP05
CH3
CH3
OR
DP10
Mn = 5,100
Pd = 1.18
C
H2
Mn = 4,300
Pd = 1.20
Reactions of Poly(t-BMA)
Two post-polymerization reactions were performed on the poly(t-BMA): the first was removal of
the dithiobenzoate end group to give a thiol end group; the second was deprotection of the t-butyl group
to give the carboxyl acid group. These reactions are summarized in Scheme 2.
The product from the reaction removing the dithiobenzoate end group (DP11) was analyzed using
GPC and proton NMR. The GPC results show a molecular weight of 7,200 and a polydispersity of 1.21.
This increase in molecular weight indicates the possibility of coupling—where two polymer chains
combine. The proton NMR spectrum shows no peaks around 7.5 ppm, which means that there is an
absence of aromatic rings in the sample, showing that the reaction was successful.
The product from the deprotection reaction (DP07) was analyzed using solubility tests in water,
chloroform, tetrahydrofuran (THF), and dimethylsulfoxide (DMSO). The compound was found to be
56
Scheme 2. Reactions of Poly(t-BMA)
S
CH3
S
C
CH2
n
C
DP05
C
CH3 H N
2
NH2
CHCl3, 40°C
CN
O
soluble in water and DMSO, but not
CH3
CH3
O
HS
C
CH3
CH2
n
C
O
C
CH3
in THF and chloroform.
These
solubility results indicate that the
CN
O
polymer was successfully deprotected,
DP11
as the removal of the protecting group
1,4 dioxane
reflux
H2O, HCl
reflux
1,4 dioxane
H2O, HCl
would have changed its polarity. The
1
H NMR spectrum obtained from the
CH3
S
CH3
S
C
CH3
CH2
C
DP07
O
HS
n
C
CH3
CN
C
CH3
CH2
C
O
n
C
CN
OH
Desired Product
product was matched to that of the
CH3
known compound.5 This also indicates
that the reaction was successful.
OH
Reactions of Poly(BMA)
The post-polymerization reaction performed on the poly(BMA) was the removal of the
dithiobenzoate end group to give a thiol end group (DP13). GPC analysis of the final product indicated a
molecular weight of approximately 4,800 and a polydispersity of 1.29. Since the weight is a little above
that of the original polymer, there might be some coupling. A drastic color change from pink (DP10) to
light yellow (DP13) indicates that the diothiobenzoate end group was removed.
Conclusion:
Two methacrylate polymers, poly(t-BMA) and poly(BMA) have been successfully synthesized
by RAFT polymerization. The polymers have been grown to the appropriate lengths and have low
polydispersities.
In addition, the dithiobenzoate group has been successfully removed from both
polymers, and the protecting t-butyl group has been removed from the poly(t-BMA). The goal for the
future is to be able to conduct both reactions on poly(t-BMA) in a sequential fashion to produce
poly(methacrylic acid), the desired product. For poly(BMA), hydrogenation needs to be performed to
yield poly(methacrylic acid).
1
Class of 2006, Department of Chemistry, Clarkson University, Honors Program, Poster Presentation
Project Advisor, Department of Chemistry, Clarkson University
3
Chiefari, J., et. al. Living Free-Radical Polymerization by Reversible Addition-Fragmentation Chain Transfer:
The RAFT Process, Macromolecules 1998.
4
Maeda, M., Kumano, A., and Tirrell, D. H+-Induced Release of Contents of Phosphatidylcholine Vesicles Bearing
Surface-Bound Polyelectrolyte Chains, J. Am. Chem. Soc. 1988.
5
Kim, J. and Tirrell, D. Synthesis of Well-Defined Poly (2-ethylacrylic acid). Macromolecules 1999.
2
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