Tagging alcohols with cyclic carbonate: A versatile equivalent of (meth)acrylate for ring-opening polymerization

Article abstract of DOI:10.1039/b713925j

Cyclic carbonate monomers based on a single biocompatible scaffold allow for incorporation of a wide range of functional groups into macromolecules via ring-opening polymerization. The Royal Society of Chemistry.

Full text of DOI:10.1039/b713925j

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Tagging alcohols with cyclic carbonate: a versatile equivalent of
(meth)acrylate for ring-opening polymerization{
Russell C. Pratt,a Fredrik Nederberg,ab Robert M. Waymouthb and James L. Hedrick*a
Received (in Berkeley, CA, USA) 11th September 2007, Accepted 11th October 2007
First published as an Advance Article on the web 25th October 2007
DOI: 10.1039/b713925j
Cyclic carbonate monomers based on a single biocompatible
scaffold allow for incorporation of a wide range of functional
groups into macromolecules via ring-opening polymerization.
Acrylic and methacrylic polymers are ubiquitous in modern
applications due to the wide variety of properties that can be
introduced by variation of the pendant groups. The wide variety of
commercially available monomers, coupled with recent advances
in controlled radical polymerization techniques, have enabled the
generation of new classes of well-defined functional macromole-
cules. In comparison, the inventory of cyclic ester and carbonate
monomers available and suitable for ring-opening polymerization
Scheme 1 Derivatization of alcohols with (meth)acrylate for radical
(ROP) is more limited. Methods have been developed for the
polymerization (top) compared with cyclic carbonate for ring-opening
synthesis of functional lactones1–5 and cyclic carbonates6 but there
polymerization (bottom).
is as yet no widely adapted method for incorporating arbitrary
functional groups into these ROP monomers.
via substitution, cycloaddition, and amide or disulfide linkages, or
for introducing strongly hydrophilic or hydrophobic groups
(Scheme 3).
To provide a more versatile and accessible library of ROP
monomers, we have exploited recently developed organocatalytic
methods for ROP of cyclic carbonate monomers derived from 2,2-
bis(methylol)propionic acid (bis-MPA). Bis-MPA has proven a
versatile building block for the construction of biocompatible
dendrimers.7 The syntheses of carbonate monomers derived from
bis-MPA typically employ acetonide protection–deprotection
schemes prior to installation of the pendant functional group
prior to forming the cyclic carbonate moiety.8 Our approach
involves the synthesis of the cyclic carbonate 1 as a versatile
synthon for a family of functionalized carbonated monomers. This
synthetic scheme parallels the powerful approach of (meth)acrylate
derivatization as a means of creating monomers (Scheme 1).
The synthesis of 1 can easily be carried out on a 0.1 mol scale
(16 g) with typical laboratory apparatus following the procedures
outlined in Scheme 2.9 Two procedures for the coupling of 1 to
alcohols were used: either direct coupling using DCC, or
conversion to the acyl chloride using oxalyl chloride followed by
reaction with the alcohol or amine in the presence of base. The
latter method has the advantage that the salt byproducts are easily
removed. Compared to methods wherein the functional group is
attached prior to carbonate formation, the inverse sequence
described here more generally requires only a single unique
reaction and purification step for new pendant groups. Using these
methods, a range of functional groups could be incorporated to
generate new ROP monomers offering opportunities for couplings
To test the suitability of these bis-MPA-derived monomers for
polymerization, we examined the organocatalytic ROP of mono-
mer 1a bearing a simple benzyl group for comparison to the
archetypical carbonate monomer, trimethylene carbonate
(TMC).10 As summarized in Table 1, both the two-component
catalyst consisting of the Lewis acid 1-(3,5-bis(trifluoromethyl)-
phenyl)-3-cyclohexyl-2-thiourea (TU) with the Lewis base 1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU) or alternatively the superba-
aIBM Almaden Research Center, 650 Harry Road, San Jose, CA, USA
95120. E-mail: hedrick@almaden.ibm.com; Fax: (1)408-927-3310
bDepartment of Chemistry, Stanford University, Stanford, CA, USA
94305
{ Electronic supplementary information (ESI) available: Synthetic details
and characterization for 1b–1j monomers. See DOI: 10.1039/b713925j
Scheme 2 Synthesis of 1-type monomers from bis-MPA. Conditions: (i)
BnBr, KOH, DMF, 100 uC, 15 h, 62%. (ii) Triphosgene, pyridine, CH2Cl2,
278 A 0 uC, 95%. (iii) Pd/C (10%), H2 (3 atm), EtOAc, RT, 24 h, 99%.
(iv) ROH, DCC, THF, RT, 16 h. (v) (COCl)2, THF, RT, 1 h, 99%. (vi)
ROH, NEt3, RT, 3 h.
114 | Chem. Commun., 2008, 114–116
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Table 2 Random copolymerizations of TMC with 1-derived mono-
mers
c
Conversion Conversion
Mn
/
Mw/
c
Comonomera Time/h TMCb (%) comonomerb (%) g mol21 Mn
1b
1g
1h
1i
a
1
4
1
4
1
4
1
4
61
95
46
91
49
92
60
91
.95
.95
.95
.95
.95
.95
.95
.95
4700
6500
3900
5700
5300
7800
6100
8600
1.10
1.11
1.07
1.07
1.09
1.11
1.05
1.05
Conditions: 1 M monomer in CH2Cl2, 80 : 20 TMC : comonomer
(mol : mol), 0.02 M PyBuOH, 0.05 M TU, 0.05 M DBU, 20 uC.
b
c
By 1H NMR spectroscopy. By GPC vs. polystyrene standards,
uncorrected.
for the homopolymerizations of TMC and 1a described above
(Table 2). Monitoring experiments (1H NMR spectroscopy) reveal
that all of the 1b–1i comonomer was incorporated into polymer
within 1 h, while the conversion of TMC lagged and did not reach
.90% conversions until after 3 h. The relative reactivities match
the higher reactivity found for 1a vs. TMC in homopolymeriza-
tion, and suggest that gradient copolymers are formed. The
observation that these polymerizations continue on after complete
consumption of the faster-reacting monomer contrasts with
behavior we have observed for random copolymerizations of
lactones, in which the faster reacting monomer reacts exclusively
under organocatalytic conditions.12 Block copolymers of different
carbonate repeat units can also be constructed by sequential
polymerization: for instance, following in situ formation of a
PTMC macroinitiator (conditions as per Table 1; [M]0/[I]0 = 37.5,
TU–DBU, 3 h; 86% conversion, Mn = 5900, PDI = 1.03),
monomer 1a was added to the reaction solution, and after 30 min
the chain-extended polymer was obtained (conversion = 92%
(TMC), 88% (1a); Mn = 9700, PDI = 1.08).
Scheme 3 Monomers synthesized via procedures in Scheme 2.
sic catalyst 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) showed high
conversions of 1a to polymer in relatively short times. Good
control over the molecular weight and polydispersity was achieved
with the TU–DBU co-catalyst, while TBD is more active and its
use leads to broadening of the polydispersity via transcarbonation
of the polymer chains. No scrambling of the pendant benzyl ester
into the poly(1a) chains could be observed using 1H-NMR
spectroscopy. While excessively bulky substituents (e.g. 2,2-
diphenyl) impede the ring-opening of six-membered cyclic
carbonates,8a,11 the increased rate of polymerization for 1a when
compared to TMC indicates that the methyl and carboxylate
substituents are well-suited for polymerization. The location of
steric bulk distant from the polymerizing carbonate also avoids
interference with the organocatalysts; substituents in the a-position
of cyclic ester monomers dramatically reduce the rates of
polymerization when organocatalysts are used, making them
incompatible with effective derivatization strategies using a-chloro
and a-azido groups.
In summary, a general synthetic route to incorporate a broad
range of functional groups into cyclic carbonate monomers has
been developed. These monomers can be polymerized under mild,
one-pot conditions to create random or block copolymers. Further
studies are underway to complete procedures for full deprotection
and derivatization of polar sidegroups once they are incorporated
into polymers.
Random copolymerizations of the cyclic carbonates with TMC
were conducted using organocatalytic procedures similar to those
Notes and references
Table 1 Organocatalytic polymerizations of 1a vs. TMC
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Monomera Catalystb Time/h Conv.c (%) Mnd/g mol21 Mw/Mn
d
1a
TU–DBU 0.5
93
94
95
11 600
11 500
12 900
13 200
8000
1.12
1.15
1.20
1.52
1.76
TU–DBU
TU–DBU
TBD
1
2
5 min 95
1
TBD
96
TMC
TU–DBU
TU–DBU
TU–DBU
TBD
1
2
3
45
74
90
4400
7300
8600
8900
11 000
1.03
1.03
1.03
1.08
1.31
5 min 98
98
TBD
1
a
Conditions: 1 M monomer in CH2Cl2 with 0.02 M PyBuOH, 20 uC.
TU–DBU: both 0.05 M; TBD: 0.01 M.
b
c
By 1H NMR
d
spectroscopy. By GPC vs. polystyrene standards, uncorrected.
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