Synthesis of side-chain functional polyesters via Baylis-Hillman polymerization

Article abstract of DOI:10.1021/ma2006238

Strategies that allow access to side-chain functional polyesters are valuable as they would enable to engineer the properties of these hydrolytically degradable materials. This contribution explores the feasibility of a novel approach toward side-chain functional polyesters that is based on the Baylis-Hillman reaction, which involves the base-catalyzed condensation of an aldehyde and an acrylate building block to produce an α-methylene-β- hydroxycarbonyl compound. Using 1,3-butanediol acrylate and 2,6- pyridinecarboxaldehyde as monomers and DABCO as catalyst, polymers with a degree of polymerization of up to 25 could be prepared. These polymers are attractive as they contain chemically orthogonal side-chain hydroxyl and vinyl groups that can be further modified. In the first experiments, it was demonstrated that the side-chain hydroxyl and vinyl groups can be quantitatively postmodified with phenyl isocyanate and methyl-3-mercaptopropionate, respectively. As the Baylis-Hillman polymerization does not require the use of side-chain protected monomers, this route may represent an interesting alternative strategy for the preparation of side-chain functional polyesters.

Full text of DOI:10.1021/ma2006238

ARTICLE
pubs.acs.org/Macromolecules
Synthesis of Side-Chain Functional Polyesters via BaylisꢀHillman
Polymerization
Sanhao Ji,† Bernd Bruchmann,‡ and Harm-Anton Klok*,†
†
ꢁ
Laboratoire des Polymꢀeres, Institut des Matꢁeriaux and Institut des Sciences et Ingꢁenierie Chimiques, Ecole Polytechnique Fꢁedꢁerale de
Lausanne (EPFL), B^atiment MXD, Station 12, CH-1015 Lausanne, Switzerland
‡Polymer Research, BASF SE, D-67056 Ludwigshafen, Germany
S Supporting Information
b
ABSTRACT: Strategies that allow access to side-chain func-
tional polyesters are valuable as they would enable to engineer
the properties of these hydrolytically degradable materials. This
contribution explores the feasibility of a novel approach toward
side-chain functional polyesters that is based on the BaylisꢀHillman reaction, which involves the base-catalyzed condensation of an
aldehyde and an acrylate building block to produce an R-methylene-β-hydroxycarbonyl compound. Using 1,3-butanediol acrylate
and 2,6-pyridinecarboxaldehyde as monomers and DABCO as catalyst, polymers with a degree of polymerization of up to 25 could
be prepared. These polymers are attractive as they contain chemically orthogonal side-chain hydroxyl and vinyl groups that can be
further modified. In the first experiments, it was demonstrated that the side-chain hydroxyl and vinyl groups can be quantitatively
postmodified with phenyl isocyanate and methyl-3-mercaptopropionate, respectively. As the BaylisꢀHillman polymerization does
not require the use of side-chain protected monomers, this route may represent an interesting alternative strategy for the preparation
of side-chain functional polyesters.
Scheme 1
’ INTRODUCTION
Aliphatic polyesters such as polyglycolide, polylactide, poly-
caprolactone, and their copolymers are attractive materials,
which have received widespread interest for applications that
require hydrolytically degradable materials. To tune the proper-
ties of these materials, e.g., their degradation behavior and to add
further functionality, there is significant interest in synthetic
strategies than can be used to prepare side-chain functionalized
polyesters.1
The side-chain functionalized polyestersthathavebeenprepared
until now have either been obtained by ring-opening polymerization
of functionalized lactones2ꢀ5 or via step polymerization of appro-
priate side-chain protected diacid or diol building blocks.6ꢀ8
Although these strategies have been successfully used, both of
them rely on monomers that are only accessible via multistep
synthesis and also require a final reaction step to deprotect the
side-chain functional groups, which bears the possible risks of
main chain degradation and incomplete deprotection.
In this contribution, we report an alternative approach for the
synthesis of side-chain functional polyesters, which is based on
the BaylisꢀHillman polymerization of bifunctional acrylates and
bifunctional dialdehydes (Scheme 1). The BaylisꢀHillman reac-
tion involves the base catalyzed reaction of R,β-unsaturated
carbonyl compounds with aldehydes to form R-methylene-β-
hydroxycarbonyl compounds.9ꢀ11 This reaction has attracted
interest in organic synthesis as it is an atom-economical carbonꢀ
carbon bond forming reaction that can be carried out with
control over stereochemistry and generates a polyfunctional
scaffold that can be converted in a variety of other products.
For polymer synthesis, in contrast, the BaylisꢀHillman reaction is
largely unexplored. Apart from a preprint by Venkitasubramanian
et al., who described the polymerization of 5-hydroxymethylfurfural
acrylate,12,13 no systematic and in-depth studies have been reported
to the best of our knowledge that investigate the feasibility of this
reaction for the synthesis of functional polyesters.
The BaylisꢀHillman reaction, however, has a number of
characteristics that make it an interesting candidate for the
synthesis of side-chain functional polyesters (Scheme 1): (i) since
the side-chain functional groups are generated during the CꢀC
bond forming process, BaylisꢀHillman polymerization does not
necessitate the use of side-chain protected monomers; (ii) the
BaylisꢀHillman reaction produces two chemically orthogonal
side-chain functional groups, viz. a vinyl group and a hydroxyl
group, which can be further modified via appropriate postpoly-
merization modification.14 This contribution investigates the
feasibility of the BaylisꢀHillman polymerization of diacrylates
and dialdehydes to prepare side-chain functional polyesters and
Received: March 17, 2011
Revised:
May 1, 2011
Published: June 08, 2011
r
2011 American Chemical Society
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Table 1. Overview of Reaction Conditions Evaluated for the BaylisꢀHillman Polymerization of 1 and 2 as Well as GPC Number-
Average and Weight-Average Molecular Weights and Number-Average Degrees of Polymerization (DPn) of the Resulting
Polymers (Monomer Concentration: 5 mol/L)
a
a
procedure
catalyst
reaction time (h)
Mna (g/mol)
Mwa (g/mol)
Mw/Mn
DPn
1
1
1
1
1
2
2
2
2
2
3
4
5
6
7
DABCO
3
6
1900
3100
4200
3800
3900
2700
3000
2500
2100
1800
630
3100
5600
9050
8000
8100
5100
5900
5200
3700
3600
800
1.6
1.8
2.1
2.0
2.1
1.9
1.9
2
11
19
25
23
23
16
18
15
6
DABCO
DABCO
DABCO
DABCO
3-HQD
3-HQD
3-HQD
3-HQD
3-HQD
DBU
24
48
72
3
6
24
48
72
24
24
24
24
24
1.8
2
11
4
1.3
1.9
1.8
1.6
1.3
DMAP
1400
1300
1800
1500
2700
2300
3000
2000
8
PPh3
4
DABCO/La(OTf)3
11
DABCO
9
a Number-average (Mn) and weight-average (Mw) molecular weight, polydispersity (Mw/Mn), and number-average degree of polymerization (DPn)
determined from GPC (THF, conventional calibration, polystyrene standards).
explores the subsequent postpolymerization modification of
these polymers to further enhance their functionality. The
present study consists of three parts, which subsequently focus
on identifying the most optimal polymerization conditions and
the characterization of the synthesized polymers as well as their
postpolymerization modification to generate multifunctional
side-chain polyesters.
chemical shifts are reported in ppm relative to the solvent’s residual
1H signal (CDCl3: 7.25 ppm). 1H NMR assignments were confirmed by
2D-COSY-45 spectra. Coupling constants J are given in hertz. 13C NMR
spectra were recorded at 101 MHz. The 13C signal of the solvent
(CDCl3: 77 ppm) was used as internal reference. Coupling constants (J)
are given in Hz. MALDI-TOF mass spectrometry was carried out on an
Axima CFR-Plus instrument (Shimadzu Biotech) operated in posi-
tive reflectron and linear modes. Sample solutions were prepared
with either R-cyano-4-hydroxycinnamic acid (CHCA, 20 mg/mL) or
2,5-dihydroxybenzoic acid (DHB, 20 mg/mL) as the matrix in the
presence of NaI. 0.5 μL of sample solution was mixed on the target with
0.5 μL of matrix solution and allowed to air-dry. External calibration was
carried out with a mixture of seven peptides (CHCA, CHCA dimer,
reserpine, angiotensin 2, substance P, Glu fib, ACTH frag 18ꢀ39,
melittin, chain B Ins). Data processing was performed using the Kompact
v2.4.3 software. ESI-MS analysis was performed on a Finnigan SSQ
710C single quadrupole mass spectrometer (Finnigan-MAT, Bremen,
Germany) equipped with an electrospray (ES) ionization interface.
Data were acquired using the ICIS software running on a Digital Unix
workstation.
’ EXPERIMENTAL SECTION
Materials. All reagents and solvents were of commercial grade and
used as received. 2,6-Pyridinedimethanol was obtained from Acros. All
other chemicals and reagents were acquired from Sigma-Aldrich (Buchs,
Switzerland). Deuterated solvents for NMR spectroscopy were acquired
from Armar Chemicals (D€ottigen, Switzerland).
Analytical Methods. Gel permeation chromatography (GPC)
analysis in THF was performed on a Waters 150CV instrument
equipped with RI and variable wavelength UV detection. Two Styragel
HR-2 and HR-3 columns connected in series were used for the separa-
tion. The interdetector volumes were calibrated with Irganox 1015, an
antioxidant from BASF SE with a molecular weight of 1177 g/mol. For
each analysis, 0.05 mL of a 5 mg/mL sample solution was injected.
Molecular weights were determined using a conventional calibration
curve, which was created with narrow polydispersity polystyrene stan-
dards. GPC analysis in DMF was carried out on a Waters Alliance GPCV
2000 system equipped with refractive index, differential viscometer,
and light scattering detectors. Separation was carried out at 60 °C with
TSK-Gel Alpha 2500 þ 3000 þ 4000 columns, using vacuum-distilled
HPLC grade DMF þ 0.5 g/L LiCl as eluent and a flow rate of
0.6 mL/min. Molecular weights were determined using a universal
calibration curve, which was created with narrow polydispersity poly-
(methyl methacrylate) (PMMA) standards. Results were calculated with
the Empower Pro multidetection GPC software (Ver 5.00). The
interdetector volume was adjusted from the peak position of uniform
PEG oligomers. The volume of the injected loop was 0.214 mL, and the
polymer concentration was calculated to give a viscometric signal less
than 0.5% of the baseline level. NMR spectra were recorded on a Bruker
ARX-400 spectrometer. CDCl3 was used as the solvent. 1H NMR
Procedures. 2,6-Pyridinedicarboxaldehyde (2). In a 500 mL
round-bottom flask equipped with a condenser, 2,6-pyridinedimethanol
(5 g, 37 mmol) was dissolved in hot CHCl3 (250 mL). The flask was
cooled to room temperature, and activated manganese oxide (60 g,
20 equiv) was added as a solid. The mixture was vigorously stirred under
reflux for 4 days until most of the starting material was consumed. After
cooling to room temperature, the suspension was filtered over Celite.
The oxidized products were purified by flash column chromatography
on silica gel, eluting with ethyl acetate and dichloromethane (1:1 v/v),
1
which afforded 2 as a white, pure solid (2.1 g, yield 42%). H NMR
(400 MHz, CDCl3): 10.16 (s, 2H), 8.16 (d, J = 7.8 Hz, 2H), 8.07
(t, J = 7.8 Hz, 1H). 13C NMR (101 MHz, CDCl3): 192.34, 152.98, 138.37,
125.32. MS (ESI): 136.96 (M þ H)þ. 1H NMR, 13C NMR, and ESI-MS
spectra are included in the Supporting Information (Figures S1ꢀS3).
Butyl-1,3-di(2-(hydroxypyridin-2-ylmethyl) Acrylate) (4). To a stirred
mixture of 2-pyridinecarboxaldehyde (285 μL, 3.0 mmol) and 1,3-butanediol
diacrylate (177.12 μL, 1.0 mmol) were added 1,4-diazabicyclo[2.2.2]octane
(DABCO) (112 mg, 1.0 mmol) and methanol (60 μL, 1.5 mmol). DMF
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Scheme 2
(0.2 mL) was added to help dissolve the reactants. The light yellow homo-
geneous reaction mixture was stirred at ambient temperature for 3 h, and the
progress of the reaction was monitored by TLC. After stirring for 3 h, the
reaction mixture was purified by flash column chromatography on silica gel,
eluting with ethyl acetate and dichloromethane (1:1 to 1:0 v/v) to give 4 as
a light yellow oil (342 mg, yield 83%). 1H NMR (400 MHz, CDCl3): 8.52
(s, 2H), 7.66 (m, 2H), 7.38 (m, 2H), 7.18 (m, 2H), 6.32 (d, J = 3.6 Hz, 2H),
5.91 (d, J = 3.8 Hz, 2H), 5.57 (t, J = 5.4 Hz, 1H), 4.98 (t, 1H), 4.84
(t, 2H, ꢀOH), 4.05 (t, 2H), 1.8 (m, 2H), 1.19 (d, J = 6.2 Hz, 3H, ꢀCH3).
13C NMR (101 MHz, CDCl3): 165.58, 165.21, 159.64, 159.48, 148, 141.77,
141.53, 136.66, 126.85, 126.66, 122.40, 121.05, 72.22, 72.04, 68.20, 60.78,
34.34, 19.64. MS (ESI): 413.2 (M þ H)þ. 1HNMR,13C NMR, and ESI-MS
spectra are included in the Supporting Information (Figures S4ꢀS6).
2-Hydroxy-[6-(1-hydroxy-2-methoxycarbonylallyl)pyridin-2-yl]-
methylacrylic Acid, 1-Methyl Ester (5). To a stirred mixture of 2,6-
pyridinedicarboxaldehyde (139 mg, 1.03 mmol) and methyl acrylate
(270 μL, 3.0 mmol) were added DABCO (112 mg, 1.0 mmol) and
methanol (60 μL, 1.5 mmol). DMF (0.2 mL) was added to help dissolve
the reactants. The light yellow homogeneous reaction mixture was
stirred at ambient temperature for 3 h, and the progress of the reaction
was monitored by TLC. After stirring for 3 h, the reaction mixture was
purified by flash column chromatography on silica gel, eluting with
ethyl acetate and hexane (1:1 v/v) to give 5 as a transparent oil
(267 mg, yield 87%). 1H NMR (400 MHz, CDCl3): 7.68 (t, J = 7.7 Hz,
1H), 7.37 (d, J = 7.8 Hz, 2H), 6.33 (s, 2H), 5.88 (s, 2H), 5.58 (d, J = 6.9 Hz,
1H), 3.72 (s, 6H), 4.37 (d, J = 7.2 Hz, 2H, OH). 13C NMR (101 MHz,
CDCl3): 166.61, 158.49, 141.41, 137.77, 126.99, 120.08, 72.57, 51.91. MS
Figure 1. GPC elugrams of samples taken at regular time intervals
during the BaylisꢀHillman polymerization of 1 and 2 (procedure 1).
spectroscopy and GPC. Samples for 1H NMR and GPC analysis were
isolated as described under Procedure 1.
Procedure 3. To a stirred mixture of 2,6-pyridinedicarboxaldehyde
(2) (124.5 mg, 0.92 mmol) and 1,3-butanediol diacrylate (1) (177 μL,
0.92 mmol) were added DBU (137 μL, 0.92 mmol) and 0.1 mL of DMF.
The homogeneous reaction mixture was stirred at ambient temperature.
The course of the reaction was followed by 1H NMR spectroscopy and
GPC. Samples for 1H NMR and GPC analysis were isolated as described
under Procedure 1.
1
(ESI): 308.2 (M þ H)þ. H NMR, 13C NMR, and ESI-MS spectra are
included in the Supporting Information (Figures S7ꢀS9).
Poly((1,3-butanediol diacrylate)-alt-(2,6-pyridinedicarboxaldehyde))
(3). Procedure 1. To a stirred mixture of 2,6-pyridinedicarboxaldehyde
(2) (135 mg, 1.0 mmol) and 1,3-butanediol diacrylate (1) (192 μL,
1.0 mmol) were added DABCO (112 mg, 1.0 mmol) and methanol
(60 μL, 1.5 mmol). 0.2 mL of DMF was added to help dissolve the
reactants, and the homogeneous reaction mixture was stirred at ambient
Procedure 4. To a stirred mixture of 2,6-pyridinedicarboxaldehyde
(2) (124.2 mg, 0.92 mmol) and 1,3-butanediol diacrylate (1) (177 μL,
0.92 mmol) were added DMAP (113 mg, 0.92 mmol) and 0.1 mL of
THF. The homogeneous reaction mixture was stirred at ambient
1
temperature. The course of the reaction was followed by H NMR
spectroscopy and GPC. Samples for 1H NMR and GPC analysis were
isolated as described under Procedure 1.
1
temperature. The course of the reaction was followed by H NMR
spectroscopy and GPC. Samples for 1H NMR and GPC analysis were
isolated by taking 50 μL aliquots from the reaction mixture at deter-
mined time intervals, which were subsequently diluted with chloroform
(50 mL). The chloroform solution was washed with a saturated solution
of aqueous NaHCO3 and brine, then separated and dried over anhy-
drous Na2SO4, filtered, and concentrated under reduced pressure to give
3 as a light yellow oil. 1H NMR (400 MHz, CDCl3): 7.61 (pyridine-H,
1H), 7.26 (pyridine-H, 2H), 6.27 (=CH2, 2H), 5.84 (=CH2, 2H), 5.54
(ꢀCHꢀOH, 2H), 4.91 (ꢀCHꢀCH3, 1H), 4.73 (ꢀOH, 2H), 3.93
(ꢀOꢀCH2ꢀCH2ꢀ, 2H), 1.77 (ꢀOꢀCH2ꢀCH2ꢀ, 2H), 1.12
(ꢀCHꢀCH3, 3H). 13C NMR (101 MHz, CDCl3): 165.72, 158.91,
142.12, 137.40, 126.24, 119.73, 71.87, 68.15, 60.79, 34.37, 19.67. A 13C
NMR spectrum is included in the Supporting Information (Figure S10).
Procedure 2. To a stirred mixture of 2,6-pyridinedicarboxaldehyde
(2) (109.8 mg, 0.81 mmol) and 1,3-butanediol diacrylate (1) (154 μL,
0.80 mmol) were added 3-HQD (112 mg, 0.87 mmol) and methanol
(60 μL, 1.5 mmol). 0.15 mL of DMF was added to help dissolve the
reactants, and the homogeneous reaction mixture was stirred at ambient
Procedure 5. To a stirred mixture of 2,6-pyridinedicarboxaldehyde
(2) (138.3 mg, 1.02 mmol) and 1,3-butanediol diacrylate (1) (197 μL,
1.02 mmol) under nitrogen were added triphenylphosphine (60 mg,
0.3 mmol) and methanol (60 μL, 1.5 mmol). 0.2 mL of THF was added
to help dissolve the reactants, and the homogeneous reaction mixture
was stirred at ambient temperature. The course of the reaction was
1
1
followed by H NMR spectroscopy and GPC. For H NMR and
GPC analysis, 50 μL aliquots were taken from the reaction media at
determined time intervals. Samples were isolated by precipitation by
addition of 50 mL of cold diethyl ether and subsequent centrifugation,
which afforded 3 as light yellow oil.
Procedure 6. To a stirred mixture of 2,6-pyridinedicarboxaldehyde
(2) (134.9 mg, 0.99 mmol) and 1,3-butanediol diacrylate (1) (191 μL,
0.99 mmol) were added DABCO (111.4 mg, 0.99 mmol), lanthanum
triflate (30 mg, 0.05 mmol), and triethanolamine (66 μL, 0.5 mmol).
0.2 mL of DMF was added to help dissolve the reactants, and the
homogeneous reaction mixture was stirred at ambient temperature. The
course of the reaction was followed by 1H NMR spectroscopy and GPC.
1
temperature. The course of the reaction was followed by H NMR
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Figure 2. 1H NMR spectra (400 MHz, CDCl3) of (A) model compound 4, (B) polymer 3 (procedure 1, after a polymerization time of 24 h), and (C)
model compound 5.
Samples for 1H NMR and GPC analysis were isolated as described under
Procedure 1.
isocyanate (400 μL, 3.55 mmol) was added and the solution stirred for
6 h at ambient temperature. The postmodified product was precipitated
by addition of cold diethyl ether (50 mL) and isolated by centrifugation.
Polymer 6 was obtained as a transparent oil (103.3 mg, yield: 41%).
Mn = 9200; Mw/Mn = 1.4. 1H NMR spectroscopy indicated quantitative
conversion of the hydroxyl groups. 1H NMR (400 MHz, CDCl3): 7.57
(pyridine-H, 1H), 7.35 (Ar, 8H), 7.25 (pyridine-H, 2H), 6.99 (p-Ar,
2H), 6.64 (=CH2, 2H), 6.34 (=CH2, 2H), 5.71 (ꢀCHꢀOH, 2H), 4.95
(ꢀCHꢀCH3, 1H), 4.00 (ꢀOꢀCH2ꢀCH2ꢀ, 2H), 1.67 (ꢀOꢀCH2ꢀ
CH2ꢀ, 2H), 1.06 (ꢀCHꢀCH3, 3H).
Procedure 7. The polymerization was carried out in a CEM Discover
monomode microwave reactor (5 W) at 50 °C using DMF (0.2 mL)
as solvent. To a stirred mixture of 2,6-pyridinedicarboxaldehyde (2)
(129.7 mg, 0.96 mmol) and 1,3-butanediol diacrylate (1) (184 μL,
0.96 mmol) were added DABCO (108 mg, 0.96 mmol), 1-butyl-2,3-
dimethylimidazolium tetrafluoroborate (125.5 mg, 0.5 mmol), and
methanol (60 μL, 1.5 mmol). The course of the reaction was followed
1
1
by H NMR spectroscopy and GPC. Samples for H NMR and GPC
analysis were isolated as described under Procedure 1.
Postpolymerization Modification of 3 with Methyl 3-Mercaptopro-
pionate (7). Polymer 3 (256 mg, 1.54 mmol double bonds; Table 1,
procedure 1 after 6 h) was dissolved in dry THF (0.2 mL), and pyridine
(0.9 mL) was added to the mixture. Then, a large excess of methyl
Postpolymerization Modification of 3 with Phenyl Isocyanate (6).
To polymer 3 (148 mg, 0.88 mmol of hydroxyl groups; Table 1,
procedure 1 after 6 h) dissolved in dichloromethane (1.2 mL), phenyl
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which allow near to quantitative conversion within a few hours.9
These advances provide a firm basis to explore the feasibility of
the BaylisꢀHillman reaction for the synthesis of side-chain
functional polyesters. In this study, for a first series of experi-
ments, the polymerization of 1,3-butanediol diacrylate 1 and
2,6-pyridinedicarboxaldehyde 2 was investigated (Scheme 2).
These monomers were selected since the BaylisꢀHillman reac-
tion of 2-pyridinedicarboxaldehyde and methyl acrylate has been
reported to proceed with 93ꢀ100% yield.15,16 Since the poly-
merization outlined in Scheme 2 is a step polymerization, high
yielding BaylisꢀHillman coupling steps are a prerequisite to
obtain high molecular weight polymers. For the polymerization
of 1 and 2 a variety of reaction conditions was evaluated, and the
resulting polymers were analyzed by GPC. The results of these
experiments are summarized in Table 1. All polymerizations
listed in Table 1 were carried out in DMF, which is a good solvent
for both monomers and the polymer and allowed to carry out the
reaction under homogeneous conditions.
A first series of polymerization experiments (procedure 1, Table 1)
was performed at room temperature using 1,4-diazabicyclo[2.2.2]-
octane (DABCO) as catalyst and methanol as additive. Methanol
was added since it was identified in previous studies to accelerate
the BaylisꢀHillman reaction.16 Polymerization of 1 and 2 in
DMF with DABCO and methanol as additive afforded a polymer
with a molecular weight of 4200 g/mol after 24 h. Increasing the
reaction time up to 72 h did not result in a further increase in
molecular weight but instead afforded slightly lower molecular
weight materials, which could indicate a depolymerization at
prolonged reaction times. Also, further variation of the mono-
mer concentration (Table S1), polymerization temperature
(Table S2), or the solvent (Table S3) did not result in polymers
with increased molecular weights. The molecular weights, de-
grees of polymerization, and polydispersities listed in Table 1
were obtained using a conventional calibration curve that was
created with polystyrene standards. For a number of samples
prepared via procedure 1 additional GPC experiments were
carried out, which were evaluated using a conventional calibra-
tion curve. These analyses, which are included in the Supporting
Information(Table S4), affordedslightly highermolecular weights
and degrees of polymerization (e.g., a degree of polymerization of
29 instead of 25 after a polymerization time of 24 h).
To obtain further insight into the kinetics of the polymeriza-
tion under these conditions, GPC was used to monitor monomer
consumption and the evolution of molecular weight during the
first 3 h (Figure 1). The chromatograms in Figure 1 show a
broad polymer peak, which gradually shifts to lower elution
volumes with increasing reaction time and reflects the increasing
molecular weight of the polymer. In addition, monitoring the
intensity of the monomer peaks in Figure 1 indicates that 1 and 2
are quantitatively consumed after 180 min. These results are in
good agreement with literature data, which reported quantita-
tive coupling of 2,6-pyridinedicarboxaldehyde with methyl
acrylate in 2.5 h.15
Figure 3. MALDI-TOF mass spectrum of polymer 3 prepared accord-
ing to procedure 1 (polymerization time 24 h).
3-mercaptopropionate (1.7 mL, 15 mmol) was added. The solution
was stirred overnight at ambient temperature. The postmodified
polymer was precipitated by addition of cold diethyl ether (100 mL)
and isolated by centrifugation to afford 7 as obtained a transparent oil
(122.8 mg, yield: 27.8%). Mn = 2100; Mw/Mn = 1.5. 1H NMR spectro-
scopy indicated quantitative conversion of the double bonds. 1H NMR
(400 MHz, CDCl3): 7.31ꢀ7.88 (pyridine-H, 3H), 4.98 (ꢀCHꢀCH3,
1H), 4.88 (ꢀCHꢀOH, 2H), 4.09 (ꢀOꢀCH2ꢀCH2ꢀ, 2H), 3.70
(ꢀOCH3, 6H), 3.15 (ꢀCHꢀCH2ꢀSꢀ), 2.78 (ꢀCH2ꢀSꢀCH2ꢀCH2,
4H), 2.65 (ꢀSꢀCH2ꢀCH2ꢀ, 4H), 2.48 (ꢀSꢀCH2ꢀCH2ꢀ, 4H), 1.83
(ꢀOꢀCH2ꢀCH2ꢀ, 2H), 1.25 (ꢀCHꢀCH3, 3H).
Sequential Postpolymerization Modification (8). Via Polymer 6.
Polymer 6 (90 mg, 0.31 mmol double bonds) was dissolved in dry THF
(0.1 mL), and pyridine (0.2 mL) was added to the mixture. Then, a large
excess of methyl 3-mercaptopropionate (0.35 mL, 3.15 mmol) was
added. The solution was stirred overnight at ambient temperature. The
postmodified polymer was precipitated by addition of cold diethyl ether
(50 mL) and isolated by centrifugation to afford 8 as a transparent oil
(31 mg, yield: 24.4%). Mn = 5500; Mw/Mn = 1.8. 1H NMR spectroscopy
indicated quantitative conversion of the double bonds.
Via Polymer 7. To polymer 7 (105 mg, 0.36 mmol hydroxyl groups)
dissolved in dichlromethane (0.8 mL), phenyl isocyanate (163 μL,
1.5 mmol) was added, and the solution stirred for 6 h at ambient tempera-
ture. The postmodified product was precipitated by addition of cold
diethyl ether (50 mL) and isolated by centrifugation, which afforded 8 as
1
a transparent oil (59 mg, yield: 39%). Mn = 3200; Mw/Mn = 1.4. H
NMR spectroscopy indicated 42% conversion of the hydroxyl groups.
1H NMR (400 MHz, CDCl3): 7ꢀ8 (Ar, 11H), 4.98 (ꢀCHꢀCH3, 1H),
4.88 (ꢀCHꢀOH, 2H), 4.13 (ꢀOꢀCH2ꢀCH2ꢀ, 2H), 3.63 (ꢀOCH3,
6H), 3.11 (ꢀCHꢀCH2ꢀSꢀ), 2.74 (ꢀCH2ꢀSꢀCH2ꢀCH2, 4H), 2.63
(ꢀSꢀCH2ꢀCH2ꢀ, 4H), 2.54 (ꢀSꢀCH2ꢀCH2ꢀ, 4H), 1.79
(ꢀOꢀCH2ꢀCH2ꢀ, 2H), 1.16 (ꢀCHꢀCH3, 3H).
As already mentioned above, the BaylisꢀHillman reaction
has traditionally been hampered by slow reaction rates and
conversions, and lots of efforts have been devoted to develop
reaction conditions that allow to overcome these problems. In
a next series of experiments, a variety of alternative protocols for
the polymerization of 1 and 2 was evaluated and compared
with regards to the molecular weight of the resulting poly-
mers (Table 1). First, 3-hydroxyquinuclidine (3-HQD) and
1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) were evaluated as
’ RESULTS AND DISCUSSION
Polymerization. Although the BaylisꢀHillman reaction has
been reported to suffer from a limited substrate scope and long
reaction times, many advances have been made over the past
decade, and numerous examples have been reported of reaction
conditions that are applicable to a broad range of substrates and
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Scheme 3
microwave irradiation,24,25 and the use of ionic liquids25,26 as the
reaction medium. None of these modifications, however, were
found to result in an increase in polymer molecular weight as
compared to the DABCO-catalyzed polymerization of 1 and 2
(Table 1, procedures 6 and 7, and Table S6).
Table 2. Results of the Postpolymerization Modification of 3
a
a
Mn
Mw
polymer comments (g/mol) (g/mol) Mw/Mn conversionb (%)
a
3
6
8
7
8
3100
9200
5500
2100
3200
5600
12700
9800
2900
4400
1.8
1.4
1.8
1.4
1.4
Characterization. The structure of the polymers prepared via
polymerization of 1 and 2 was confirmed by 1H NMR spectro-
scopy and MALDI-TOF mass spectrometry. As an example,
100
100
100
42
via 6
via 7
1
Figure 2 shows the H NMR spectrum of polymer 3 prepared
following procedure 1 after a polymerization time of 24 h. Peak
assignments in the 1H NMR spectrum of polymer 3 were made by
comparison with the spectra of two model compounds (4 and 5),
which are also included in Figure 2. One of the most characteristic
signals in the 1H NMR spectrum of 3 is peak g at 5.53 ppm, which
is due to the CꢀH resonance of the tertiary carbon atom that is
formed during the BaylisꢀHillman coupling of 1 and 2. Further-
more, comparison of the integrals in the 1H NMR spectrum of 3,
and in particular those of signals e, f, and g, confirms that the
polymer that has been formed indeed is the result of the
BaylisꢀHillman coupling of 1 and 2. The 1H NMR spectrum of
3 reveals a number of smaller signals in close proximity to the main
peaks. Sincethe chemical shifts of severalof these peaksmatch well
with those of the model compounds, these less intense resonances
are attributed to short oligomers (di-, tri-, and tetramers, for
example) that are also formed during the polymerization.
a Number-average (Mn) and weight-average (Mw) molecular weight,
polydispersity (Mw/Mn), and number-average degree of polymerization
(DPn) determined from GPC (THF, conventional calibration, poly-
styrene standards). b Side-chain functional group conversion as deter-
mined by 1H NMR.
alternatives to replace DABCO. 3-HQD17,18 and DBU19 were
selected since they have been reported to enhance the rate of
BaylisꢀHillman reactions. The use of these catalysts for the
polymerization of 1 and 2, however, was not found to result in
polymers with molecular weights higher than those obtained via
the DABCO catalyzed polymerization (see procedures 2 and 3 in
Table 1). Similarly, replacing DABCO by 4-(dimethylamino)-
pyridine (DMAP)20 or triphenylphosphine21,22 also did not to
result in polymers with increased molecular weights (Table 1,
procedures 4 and 5). For procedures 3ꢀ5, Table 1 only lists a
single data point. Additional data that illustrate the evolution of
polymer molecular weight with reaction time for these experi-
ments are included in the Supporting Information (Table S5).
Other strategies that have been proven successful to enhance
the rate and conversion of BaylisꢀHillman reactions include
the use of lanthanum triflate as a cocatalyst,23 the application of
The structure of polymer 3 was further confirmed by MALDI-
TOF mass spectrometry. Figure 3 shows the MALDI-TOF mass
spectrum of polymer 3 prepared via procedure 1 after a poly-
merization time of 24 h. The MALDI-TOF mass spectrum
reveals two main series of peaks. Within each series, neighboring
peaks are separated by 333 Da, which is the molecular weight of a
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Figure 4. 1H NMR spectra (400 MHz, CDCl3) of (A) polymer 3 (procedure 1, polymerization time 24 h), (B) polymer 6, (C) polymer 7,
(D) polymer 8 (prepared from polymer 6), and (E) polymer 8 (prepared from 7).
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single repeat unit of polymer 3. One series of peaks in Figure 3
can be assigned to polymers containing two acrylate end groups,
whereas the other main series is due to polymers carrying one
acrylate and one aldehyde end group. Analysis of the masses for
each of the two series of peaks indicates that (one of) the
acrylate end group(s) of 3 is a zwitterionic adduct resulting
from 1,4-addition of DABCO with (one of) the acrylate end
groups.27ꢀ29 The MALDI-TOF mass spectrum in Figure 3 also
reveals series of lower intensity signals. A version of the mass
spectrum in which two of these series are assigned is included in
the Supporting Information (Figure S11).
also evident from the relatively low isolated yields as reported in
the Experimental Section. Table 2 also lists the GPC molecular
weights of the polymers 6ꢀ8. The anomalous trends in the
molecular weights of some of the samples among each other as
well as compared to the starting polymer 3 are most likely due to
differences in hydrodynamic properties and as a consequence
GPC elution behavior.
’ CONCLUSIONS
This contribution has explored the feasibility of the Baylisꢀ
Hillman reaction for the synthesis of side-chain functional
polyesters. Using 1,3-butanediol diacrylate and 2,6-pyridinedi-
carboxaldehyde as monomers and DABCO as the catalyst,
polymers with degrees of polymerization of up to 25 could be
prepared. These polymers are attractive as they contain chemi-
cally orthogonal side-chain hydroxyl and vinyl groups, which can
be further modified to generate a diverse range of functional
polyesters. In first proof-of-concept experiments, it was demon-
strated that the side-chain hydroxyl and vinyl groups can be
quantitatively modified with phenyl isocyanate and methyl-3-
mercaptopropionate, respectively. Bifunctional polyesters could
be obtained via successive postpolymerization modification of
the starting polymer with phenyl isocyanate and methyl-3-
mercaptopropionate. The results of this study indicate that the
BaylisꢀHillman polymerization represents an interesting alter-
native approach to synthesize side-chain functional polymers,
which complements e.g. the ring-opening polymerization of
functional lactones or the step polymerization of functional
diacid or diol building blocks. In contrast to the latter two
approaches, the BaylisꢀHillman polymerization does not neces-
sitate the use of side-chain protected monomers and generates
polymers that contain two chemically orthogonal side-chain
functional groups, which can be further modified to generate a
vast diversity of functional polyesters. While the relatively low
molecular weight polymers reported in this contribution may be
of interest, e.g., as dual cure coatings, further work may lead to
increased molecular weights and could further expand the
possible scope of applications of these materials.
Postpolymerization Modification. One of the attractive
features of polymer 3 is that it contains two chemically orthogonal
handles, viz. a vinyl group and a hydroxyl group, which can be
further modified with various reagents to generate a broad variety
of side-chain functional polyesters. As a first proof-of-concept, the
postpolymerization modification of 3 with methyl-3-mercapto-
propionate and phenyl isocyanate was investigated (Scheme 3).
Both the single postpolymerization modification of 3 with
phenyl isocyanate and methyl-3-mercaptopropionate to afford
polyesters 6 and 7, respectively, as well as the two-step modifica-
tion of 3 to produce the double functionalized polyester 8 were
investigated. The postpolymerization modification reactions
1
were monitored with H NMR spectroscopy and GPC, and
the results of these experiments are summarized in Table 2 and
1
Figure 4. Comparison of the H NMR spectra of the starting
polymer 3 with those of 6 and 7 indicates that the single step
postpolymerization modification proceeds smoothly with quan-
titative conversion of the side-chain double bonds and hydroxyl
groups in 3, respectively. Quantitative postpolymerization modi-
fication of the side-chain double bonds is evident from the
absence of the olefinic protons b and c in the 1H NMR spectrum
of 7 and is also supported by comparison of the integral of
signals f and k in the 1H NMR spectrum of 7. The modification
of the side-chain hydroxyl groups of 3 results in a shift of the
proton resonance of d as well as additional signals between 7
and 7.5 ppm, which are due to the phenyl carbamate side chain
of 6. Comparison of the signals k and a in the 1H NMR spectrum
of 6 suggests that this postpolymerization modification reaction
also proceeds quantitatively. Subsequent postpolymerization
modification of 6 with methyl-3-mercaptopropionate proceeded
with quantitative conversion of the double bonds as is evidenced
by the absence of 1H NMR resonances b and c in the correspond-
’ ASSOCIATED CONTENT
S
Supporting Information. GPC chromatograms, ESI-MS
b
1
spectra, and NMR spectra. This material is available free of
charge via the Internet at http://pubs.acs.org.
ing H NMR spectrum of 8. The alternative pathway to 8 via
postpolymerization modification of 7 turned out to be less
efficient. Reaction of 7 with phenyl isocyanate only resulted in
42% conversion of the hydroxyl groups as calculated by compar-
ison of the 1H NMR integrals of peak a (6.8ꢀ7.2 ppm, from the
phenyl ring at the side chain) and peak k (1.5ꢀ2 ppm, from the
backbone). It should be noted here, however, that the resolution
of the 1H NMR spectra in Figure 4D and E is not excellent. The
integral of signal a in the spectrum in Figure 4D is also lower than
expected, and as a consequence it seems likely that the actual
hydroxyl group conversion in 8 in Figure 4E is higher than 42%,
although certainly not quantitative. The GPC chromatograms of
the postmodified polymers 6, 7, and 8 all revealed monomodal
molecular weight distributions, which in several cases were
narrower than those of the starting polymer 3 (Supporting
Information, Figures S12 and S13). This is most likely due to
fractionation that occurred during work-up and isolation of
the postmodified polymer, which involved precipitation. Frac-
tionation inherently leads to loss of some of the material, which is
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: harm-anton.klok@epfl.ch; Fax: þ 41 21 693 5650; Tel:
þ 41 21 693 4866.
’ ACKNOWLEDGMENT
This research was supported by BASF SE. S.J. thanks Dr.
Frederik Wurm and Dr. Matthew Gibson for helpful discussions
and Dr. Quoc Tuan Nguyen for his help with the GPC analysis.
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