Synthesis and functionalization of vinylsulfide and ketone-containing aliphatic copolyesters from fatty acids

Article abstract of DOI:10.1016/j.polymer.2015.10.024

A series of novel aliphatic copolyesters bearing vinylsulfide and ketone functional groups were synthesized via lipase catalyzed polycondensation of vegetable oil derivatives. The vinylsulfide-containing hydroxyacid (VSHA) from 10-undecenoic fatty acid and the ketone-containing hydroxyester (KHE) from methyl oleate were used to obtain random copolymers and further sequential and single-step strategies involving the reactions with thiol and oxyamine were investigated. Good agreement between product and feed stoichiometries was achieved in both reactions for sequential modification, and the order of addition seems not to be a significant parameter. One pot functionalization allows for the single step modification, but not quantitative reactions were achieved.

Full text of DOI:10.1016/j.polymer.2015.10.024

Accepted Manuscript
Synthesis and functionalization of vinylsulfide and ketone-containing aliphatic
copolyesters from fatty acids
Zeynep Beyazkilic, Gerard Lligadas, Juan Carlos Ronda, Marina Galià, Virginia Cádiz
PII:
S0032-3861(15)30310-4
10.1016/j.polymer.2015.10.024
JPOL 18191
DOI:
Reference:
To appear in: Polymer
Received Date: 31 July 2015
Revised Date: 8 October 2015
Accepted Date: 9 October 2015
Please cite this article as: Beyazkilic Z, Lligadas G, Ronda JC, Galià M, Cádiz V, Synthesis and
functionalization of vinylsulfide and ketone-containing aliphatic copolyesters from fatty acids, Polymer
(2015), doi: 10.1016/j.polymer.2015.10.024.
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ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Synthesis and functionalization of vinylsulfide and ketone-containing
aliphatic copolyesters from fatty acids
Zeynep Beyazkilic, Gerard Lligadas, Juan Carlos Ronda, Marina Galià,
Virginia Cádiz
Departament de Química Analítica i Química Orgànica, Universitat Rovira i
Virgili, C/Marcel.lí Domingo 1, 43007 Tarragona, Spain
Correspondence to: Author Name (e-mail:marina.galia@urv.cat)
ABSTRACT
A series of novel aliphatic copolyesters bearing vinylsulfide and ketone
functional groups were synthesized via lipase catalyzed polycondensation of
vegetable oil derivatives. The vinylsulfide-containing hydroxy acid (VSHA) from
10-undecenoic fatty acid and the ketone-containing hydroxy ester (KHE) from
methyloleate were used to obtain random copolymers and further sequential
and single-step strategies involving the reactions with thiol and oxyamine were
investigated. Good agreement between product and feed stoichiometries was
achieved in both reactions for sequential modification, and the order of addition
seems not to be a significant parameter. One pot functionalization allows for the
single step modification, but not quantitative reactions were achieved.
INTRODUCTION
Aliphatic polyesters continue receiving significant attention in the design and
construction of synthetic materials for use in biomedical applications due to their
biocompatibility and biodegradability. Poly(lactic acid), poly(ε-caprolactone),
poly(buthylene succinate) and poly(buthylene sucinate-co-buthylene adipate)
are increasingly becoming important giving that they have thermoplastic
processability and thermomechanical properties.1 However, their versatility and
successful use as commodity plastics is limited as is their exploitation in
biomedical, electronic and optical sectors. The absence of reactive
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functionalities on the polymer backbone greatly limits their use in a series of
demanding applications where the precise control and placement of
functionality is critical. The introduction of functional groups on the backbone
can modulate the physical, chemical and biological properties of polyesters.
However, the synthesis of functional aliphatic polyesters remains a challenge in
polymer science.2
In recent years, a varity of strategies for the functionalization of synthetic
polyesters via copolymerization with specialty monomers, postpolymerization
modification or a combination of these two strategies have emerged.3 The
copolymerization with functional monomers offers a high degree of
functionalization but important aspects to consider are the monomer reactivity
and how the functionality is spread through the polymeric chain. This approach
includes the polymerization of monomers with moieties that are inert towards
the polymerization conditions, but which can be quantitatively converted into a
broad range of functional groups. In this way, a simple polyester platform with a
versatile chemistry for coupling of numerous pendant units could allow for the
construction of multifunctional materials.
Ideally, the modification reactions must be highly efficient and occur without the
use of harsh reactions conditions and reagents. The reaction environment
should be sufficiently mild to avoid premature degradation of the polymer while
allowing for the incorporation of small molecules ligands or polymers onto the
polymer backbone. The choice of highly efficient chemistry would improve the
consumption of the polymer and the reagents and produce a more pure
product, as it is often difficult to remove non reacted unities remaining in the
desired material. Moreover, when working with a hydrolytically degradable
polymer the ability to incorporate different units in a single step to afford a
multifunctional copolymer is beneficial, as it minimizes the premature
degradation of the polyester backbone that may result from sequential
functionalization reactions.
To avoid polymerization methods that often require toxic chemical catalysts,
enzyme-catalyzed polymerization provides a strategy for producing useful
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polymeric materials with many advantages including mild reaction conditions,
high tolerance of functional groups, high catalyst activity and the use of nontoxic
biocatalysts. 4 The enzymatic synthesis of biobased polyesters from renewable
resources has been reported.5 Click reactions are particularly well suited for
modification of polymer chains. Many examples of incorporation of double
bonds,6,7 triple bonds,8,9,10 thiols,11 azides,12,13 ketones14 and epoxides15 onto
polyesters backbone, amenable to react under the well known click reactions
conditions, have been described.
Moreover, from the sustainability concerns, the polyester should be synthesized
from renewable resources.16 Remarkable examples of aliphatic polyesters from
renewable resources include the ones obtained from vegetable oils.17,18 Most of
them are hydrophobic and free of functional groups for further modification.
Indeed, further reaction to introduce functionalization is a required strategy to
improve the properties of the resulting polyesters.
Our group is interested in extending the use of vegetable oils in the synthesis of
functionalized polyesters by design of specialty monomers. We previously
described the synthesis of vinyl sulfide-19 and ketone-containing20 fatty acid
derivatives and their enzymatic homopolymerizations. We demonstrated that
thiol-ene and oxime chemistries can be successfully applied to the modification
of these polyesters.
Aimed at developing a platform for the synthesis and functionalization of
renewable aliphatic polyesters, we present herein our investigations using these
two reactions for the derivatization of copolyesters, encouraged to demonstrate
how sequential postpolymerization reactions and single step strategies can be
utilized for multiple functionalization. Copolyesters of vinyl sulfide-containing
hydroxyacid (VSHA) and ketone-containing hydroxyester (KHE) (Scheme 1)
were obtained via enzymatic polymerization. These copolyesters with two
“clickable” moieties allow the application of chemoselective thiol-ene and oxime
reactions.
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EXPERIMENTAL
Materials
The following chemicals were obtained from the sources indicated and used as
received: 10-undecenoic acid (Fluka), methyl oleate (96%, Alfa Aesar), 2-
mercaptoethanol (99%, Aldrich), O-(tetrahydro-2H-pyran-2-yl)hydroxylamine
(96%, Aldrich), bromine (99%, Aldrich), p-toluenesulfonic acid monohydrate
898%, Aldrich), 4-(dimethylamino)pyridine (DMAP) (≥99%, Aldrich), 2,2-
dimethoxy-2-phenylacetophenone
(DMPA)
(99%,
Aldrich),
meso-
tetraphenylporphyrin (TPP) (Aldrich), and 1,5-diazabicyclo[4.3.0]non-5-ene
(DBN) (98%, Aldrich). Solvents were purified by standard procedures.
Novozyme-435, lipase acrylic resin from candida Antarctica (Aldrich), was dried
under vacuum for 24h before use.
Synthesis of vinylsulfide-containing hydroxyacid VSHA19
a) Synthesis of 10-Undecynoic Acid
In a 1000 ml two-necked round bottom flask provided with a Teflon-coated
magnetic bar and a pressure equalized dropping funnel, 10-undecenoic acid
(46.0 g, 0.25 mol) and diethyl ether (500 mL) were placed. To this solution,
bromine (48 g, 300 mmol) was added with stirring at 0°C during 75 min. The
mixture was allowed to warm up gradually to room temperature and after stirring
overnight, the solvent and the excess of bromine were removed at reduced
pressure. To a 2L round-bottomed flask the brown liquid dibromo acid was
transferred, n-propanol (800 mL) and 85% aqueous potassium hydroxide (1.8
mol, 120 g in 140 ml water) were added and the mixture was refluxed for 20 h.
Then, water (1500 mL) was added and the cold solution was neutralized with 2
N (≈ 800 ml) hydrochloric acid solution. After several extractions with diethyl
ether the combined organic phases were dried with anhydrous magnesium
sulfate and the solvent was evaporated under reduced pressure. The residue
was distilled under reduced pressure (0.5 mmHg) and the fraction at 120-130
°C was collected. The product solidifies on cooling and was recrystallized from
hexane to obtain a white solid (yield 70%, mp 41-42 °C).
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1H NMR (CDCl3, δ, ppm): 11.10 (s, 1H), 2.35 (t, 2H), 2.18 (dt, 2H), 1.94 (t, 1H),
1.67-1.29 (m, 12H)
13C NMR (CDCl3, δ, ppm): 180.6 (s), 84.9 (s), 68.3 (d), 34.3 (t), 28.5-24.8 (t),
18.5 (t)
b) Thiol-yne addition to 10-Undecynoic acid
A mixture of 10-undecynoic acid (1.00 g, 5.50 mmol) and 2-mercaptoethanol
(0.45 g, 5.77 mmol) was heated in toluene solution at 80°C in presence of AIBN
(10 % mol init./mol C≡C) for 20 min. The product was purified by column
chromatography using hexane-ethyl acetate 1:1 as eluent to afford a mixture of
E and Z vinyl sulfides as a white solid (yield 77%, mp: 35-36ºC, E/Z ratio 1:1
from 1H NMR).
1H NMR (CDCl3, δ, ppm): 5.90-5.84 (2 dt , 1H), 5.79-5.58 (2 dt, 1H) Jtrans=14,8
Hz, Jvec=8 Hz, Jcis= 8,8 Hz, Jvec=8 Hz, 3.75 (dt, 2H), 2.84 (dt, 2H), 2.34 (t,
2H), 2.16-2.03 (dq, 2H), 1.66 (m, 2H), 1.42-1.25 (m, 10H)
13C NMR (CDCl3, δ, ppm): 179.9 (s), 133.9 (d), 131.6 (d), 123.7 (d), 121.3 (d),
61.4 (t), 60.8 (t), 36.9 (t), 36.2 (t), 34.2 (t), 33.2 (t), 29.4-24.8 (t)
Synthesis of ketone containing hydroxyester KHE20
a) Synthesis of enone derivative of methyl oleate
Enone derivative of methyl oleate has been obtained as a mixture of methyl-9-
oxo-10-octadecenoate and methyl-10-oxo-8-octadecenoate. The reactor was
charged with a solution of methyl oleate (20.0 g, 67.5 mmol), acetic anhydride
(6.68 mL, 70.8 mmol), pyridine (2.73 mL, 33.8 mmol), TPP (50.2 mg), and
DMAP (0.167 g, 1.37 mmol) in methylene chloride (325 mL). After 2 h of
irradiation, TLC (3:1 pentane/ether) indicated no remaining starting material and
an intense UV active spot for the enone. The mixture was diluted with ether (1
L) and washed successively with 100-mL portions of water, saturated NaHCO3,
1 N HCl, saturated CuSO4 water, and saturated NaCl. After drying (MgSO4) and
concentration, the dark residue was bulb-to-bulb distilled (165 °C at 0.04 mm) to
afford a 1:l mixture of methyl 9-oxo-10-octadecenoate and methyl 10-oxo-8-
octadecenoate as a light yellow liquid (yield 97%).
1H NMR (CDCl3, δ, ppm): 6.84-6.75 (m, H), 6.07 (dt, H), 3.65 (s, 3H), 2.50 (t,
2H), 2.29 (dt, 2H), 2.20 (m, 2H), 1.63-1.25 (m, 20 H), 0.86 (t, 3H)
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13C NMR (CDCl3, δ, ppm): 200.5 (s), 173.9 (s), 147.1 (d), 130.3 (d), 51.30 (q),
40.0 (t), 33.9 (t), 32.3-22.5 (t), 14.0 (q)
b) Thiol-Michael addition to enone derivative of methyl oleate
A equimolecular mixture of enone derivative (1.0 g, 3.22 mmol) and 2-
mercaptoethanol (0.3 g, 3.22 mmol) was stirred at room temperature in the
presence of DBN (0.1 % mol) for one hour. The crude product was washed with
distilled water and dried (yield 97%).
1H NMR (CDCl3, δ ppm): 3.75 (m, 2H), 3.65 (s, 3H), 3.15 (m, 1H), 2.72 (m, 2H),
2.64 (m, 2H), 2.40 (t, 2H), 2.29 (t, 2H), 1.62-1.26 (m 20H), 0.86 (t, 3H)
13C NMR (CDCl3, δ ppm): 209.8 (s), 174.4 (s), 61.5 (t), 51.6 (q), 48.7 (t), 43.9
(t), 43.8 (t) , 40.3 (t), 36.1 (d), 34.7 (t), 34.2 (t), 32.0 (t), 31.9 (t), 29.5-22.8 (t),
14.2 (q)
Synthesis of random copolymers P(VSHA-KHE)
Enzymatic copolymerizations were carried out using Novozyme-435 (10 or 20
% w/w relative to total weight of monomer). Different molar ratios of hydroxyacid
(VSHA) and hydroxyester (KHE) were copolymerized with in diphenylether
(DPE) (2:1 w/v monomer /DPE) or in bulk. Reactions were carried out at 80º or
90ºC and vacuum was applied to remove the esterifications products water and
methanol. The polymerizations were terminated by adding excess of
chloroform, stirring and removing the enzyme by filtration and precipitating in
cold methanol (yield 88-91 %).
1H NMR (CDCl3, δ, ppm): 5.90-5.85 (2 dt , 1 H), 5.74-5.55 (2 dt, 1H)
Jtrans=14,8 Hz, Jvec=8 Hz; Jcis= 8,8, Hz, Jvec=8 Hz, 4.22-4.14 (m, 4 H), 3.64
(s, 3H), 3.14 (m, 1H), 2.80 (dt, 2 H), 2.72 (m, 2H), 2.64 (m, 2H), 2.40 (t, 2H),
2.29 (dt, 4H), 2.10 (m, 2 H), 1.61-1.25 (m, 34H), 0.87 (t, 3H)
13C NMR (CDCl3, δ, ppm): 209.1 (s), 173.7 (s), 133.2 (d) , 131.0 (d), 123.9 (d),
121.5 (d), 63.7 (t), 63.0 (t), 49.0 (t), 43.8 (t), 41.2 (d), 35.7 (t), 34.3 (t), 34.2 (t),
33.3 (t), 32.0 (t), 31.9 (t), 31.4 (t), 29.8-22.8 (t), 14.2 (q)
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Sequential and one-pot functionalization of P(VSHA50KHE50)
Route A: Random copolyester P(VSHA50KHE50), (0.200 g, 0.330 mmol) was
mixed with 2-mercapthoethanol (0.064 g, 0.826 mmol) in THF and DMPA (1 %
mol) as a radical photoinitiator was added. The reaction was carried out at room
temperature,without deoxygenation by irradiation with two 9 W UV-lamps
1
(λ=365 nm). The completion of the reaction was confirmed after 30 min by H
NMR. The copolyester P(MVSHA50KHE50) (0.033 g, 0.28 mmol) was then mixed
with O-(tetra-hydro-2H-pyran-2 yl)hydroxylamine (0.017g , 0.148 mmol) in THF
and two drops of a 0.02 M p-TsOH was added. The reaction was carried out at
room temperature for 5h. The final copolyester P(MVSHA50MKHE50) was
washed with water to remove all unreacted products and dried under vacuum.
Route B: Sequential modification was carried out in the opposite order of route
A to generate first the ketoxime containing copolyester P(VSHA50MKHE50) and
followed by the thioether formation P(MVSHA50MKHE50).
Route C: The single step preparation was carried out by adding 2-
mercapthoethanol
and
O-(tetra-hydro-2H-pyran-2-yl)hydroxylamine
to
copolyester P(VSHA50KHE50) dissolved in THF with UV irradiation for 30 min
and stirring at room temperature for 7h.
a) Thiol-ene functionalization P(MVSHA50KHE50)
1H NMR (CDCl3, δ, ppm): 4.22-4.15 (m, 4H), 3.75 (t, 2H), 3.65 (s, 3H), 3.14 (m,
1H), 2.88-2.58 (m, 11H), 2.40 (t, 2H), 2.29 (dt, 4H), 1.77-1.25 (m, 36 H), 0.87 (t,
3H)
13C NMR (CDCl3, δ, ppm): 209.2 (s), 173.7 (s), 63.7 (t), 63.2 (t), 61.4 (t), 49.0
(t), 46.2 (d), 43.9 (t), 41.2 (d), 38.6 (t), 35.6 (t), 34.4 (t), 34.3 (t), 31.9 (t), 31.4 (t),
29.8-22.8 (t), 14.3 (q)
b) Oxime functionalization P(MVSHA50MKHE50)
1H NMR (CDCl3, δ, ppm): 5.90-5.85 (2 dt , 1 H), 5.74-5.55 (2 dt, 1H)
Jtrans=14,8 Hz, Jvec=8 Hz; Jcis= 8,8, Hz, Jvec=8 Hz, 5.20 (m, 1H), 4.22-4.15
(m, 4H), 3.85 (m, 1H), 3.65 (s, 3H), 3.60 (m, 1H), 3.11 – 2.91 (m, 1H), 2.80 (dt,
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2 H), 2.72 (m, 2H), 2.64 (m, 2H), 2.40 (m, 2H), 2.29 (dt, 4H), 2.10 (m, 2 H),
1.61-1.25 (m, 40H), 0.87 (t, 3H)
13C NMR (CDCl3, δ, ppm): 173.7 (s), 160.6 (s), 100.6 (d), 133.2 (d) , 131.0 (d),
123.9 (d), 121.5 (d), 63.7 (t), 63.0 (t), 62.8 (t), 43.2 (d), 40.5 (t), 38.7 (t) , 35.7
(t), 34.8 (t), 34.3 (t), 34.2 (t), 32.0 (t), 31.4 (t), 30.0-22.8 (t), 14.3 (q)
c) Thiol-ene and oxime functionalization P(MVSHA50MKHE50)
1H NMR (CDCl3, δ, ppm): 5.20 (m, 1H), 4.22-4.15 (m, 4H), 3.85 (m, 1H), 3.75 (t,
2H), 3.65 (s, 3H), 3.60 (m, 1H), 3.10 (m, 1H), 2.92-2.58 (m, 11H), 2.43-2.28 (m,
6H), 1.79-1.23 (m, 42H), 0.87 (t, 3H)
13C NMR (CDCl3, δ, ppm): 173.7 (s), 160.6 (s), 100.6 (d), 63.7 (t), 63.2 (t), 62.8
(t), 61.4 (t), 46.2 (d), 43.2 (d), 40.5 (t), 38.7 (t) , 35.7 (t), 34.8 (t), 34.3 (t), 34.2
(t), 32.0 (t), 31.4 (t), 30.0-22.8 (t), 14.3 (q)
Instrumentation
NMR spectra were recorded on a Varian VNMRS400. The samples were
dissolved in deuterated chloroform, and 1H and 13C NMR spectra were recorded
at room temperature with tetramethylsilane as an internal standard. ESI MS
were run on an Agilent 1100 Series LC/MSD instrument.
Size exclusion chromatography (SEC) analysis was carried out with a Agilent
system using THF as eluent (flow rate of 1.0 mL/min) at 35 °C . THF soluble
polymers were analyzed with an Agilent 1200 Series system equipped with an
Agilent 1100 series refractive-index detector on the following columns system:
PLgel 20ꢀm MIXED-A (20ꢀm, 7.5 mm x 300 mm), PLgel 5ꢀm MIXED-D (5ꢀm, 7.5
mm x 300 mm), PLgel 3ꢀm MIXED-E (3ꢀm, 7.5 mm x 300 mm). The calibration
curves for SEC analysis were obtained with narrow polystyrene standards from
Agilent ranging from 162 to 483 400 Da.
Differential scanning calorimetry (DSC) measurements were carried out with a
Mettler DSC822e thermal analyzer with N2 as the purge gas. Samples of 6-
12mg were used for DSC analysis. Thermal stability studies were carried out
with a Mettler TGA/SDTA851e/LF/1100 with N2 as the purge gas at a scanning
rate of 10 °C/min. The studies were performed in th e 30–800 °C temperature
range at a scan rate of 10 °C /min.
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RESULTS AND DISCUSSION
Copolyester Synthesis
Our goal was to design a series of versatile copolyesters capable of bearing
multiple functional ligands by means of a post-polymerization modification
strategy. Two comonomers were chosen (Scheme 1): VSHA was selected
because it contains a vinyl sulfide moiety capable to accept a thiol rapidly,
without any metal catalyst allowing for a variety of ligands to be covalently
inmobilized.19, 21 KHE was chosen as a monomer due to the presence of a
ketone, which has the ability to react chemoselectively with oxyamine-,
hydrazine-, and hydrazide-terminated ligands. This reaction is mild and it can
proceed rapidly at physiological conditions and without need of any co-reagents
or catalyst.14, 20, 22
Scheme 1. Copolymerization of VSHA and KHE
The synthesis was designed in view of biological applications and therefore,
copolymers were generated without any potential contaminating catalyst or co-
reagents. Novozyme-435, Candida antarctica lipase B physi-adsorbed to a
macroporous acrylic resin, was successfully used in the synthesis of poly
vinylsulfide ester derived from VSHA19 and poly ketoester from KHE.20 The
progress of the polymerization was monitored through the evolution of
molecular weight distribution obtained by SEC analysis. The SEC trace for the
control reaction in absence of Novozyme 435 verifies that chain growth occurs
due to enzyme catalysis. In this way, homopolymerization of both monomers
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with 10% of catalyst at 80 or 90 ºC and using DPE as solvent was investigated.
Molecular weight homopolymers of 70000 and 40000 g/mol-1 respectively, were
obtained after 48 h at 90ºC (Figure 1a).
Figure1. Mw versus time for a) homopolymers of VSHA and KHE in DPE; b)
copolyesters (VSHA:KHE, 1:1) in bulk c) copolyesters (VSHA:KHE, 1:1) in DPE
With this information in hand, copolymers using 1:1 molar ratio of comonomers
and 10% of catalyst were obtained by heating in bulk at 80 and 90ºC. Similar
molecular weights around 25000 g mol-1 and polydispersities of 1.6-1.8 were
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obtained after 48 h of reaction as can be seen in Figure 1b. No significant
differences were observed by increasing catalyst loading to 20% at both
temperatures (Figure 1b). Polymerizations were also carried out in the same
conditions but using 50% w/v of DPE as solvent. Higher molecular weights were
obtained by solution polymerization, according to greater constraints on chain
diffusion for bulk polymerizations and/or to an enhanced catalyst activity when
the reaction is carried out in DPE.23 Using the two monomers, copolymers of
different composition were also obtained. Molar ratios of VSHA:KHE of 1:4 and
4:1 were considered and to obtain high molecular weights and low
polydispersity indices, temperature of 90 ºC, 20% of Novozyme-435 and 50%
w/v of DPE were used. In this way, higher molecular weights were obtained in
both cases (Table 1).
Table 1. Molar composition and molecular weights of P(VSHAxKHEy)
copolyesters
Molar Composition
VSHA / KHE
Molecular Weight
(g/mol)
Polymer
Feed
ratio
4.00
1.00
0.25
1H NMRa
ratio
Mn
Mn
PDI
NMRb
32400
15500
24800
SECc
63800
27100
41000
P(VSHA80KHE20)
P(VSHA50KHE50)
P(VSHA20 KHE80)
3.88
1.9
1.7
1.6
0.98
0.32
a Molar composition determined from 1H NMR by using VSHA signal at
2.10 ppm and KHE signal at 0.87 ppm.
b
Mn values were calculated by using VSHA signal at 2.10 ppm, KHE
signal at 0.87 ppm, and end groups signal at 3.73 ppm (CH2-OH).
c THF as solvent
1
The chemical structure of the copolyesters was determined by H NMR (Figure
2a). A new signal at 4.22-4.14 ppm corresponding to the ester repeating units
appears. The presence of the vinyl thioether moiety was confirmed by the
appearance of two sets of signals between 5.55 and 5.90 ppm corresponding to
the E and Z C-C double bond protons. Moreover, the signal corresponding to
methylene protons vicinal to double bonds appear at 2.10 ppm. The presence of
KHE moiety was confirmed by signals at 3.14 ppm corresponding to the
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methine linked to sulfur, signals at 2.64 and 2.40 ppm corresponding to
methylene in α-positions to the ketone and signal at 0.87 ppm due to side chain
methyl group.
By integrating VSHA signal at 2.10 ppm and KHE signal at 0.87 ppm,
copolyester composition was calculated and resulted very close to monomer
feed (Table 1). Moreover, molecular weight was obtained from VSHA signal at
2.10 ppm and KHE signal at 0.87 ppm and end group signal at 3.73 ppm (CH2-
OH). Significant differences were noticed between the absolute molecular
1
weights calculated by H NMR and the molecular weights evaluated by SEC
using THF as solvent, giving an indication that the polystyrene standards
calibration of our system over represents the molecular weight values (Table 1).
Figure 2. 1H NMR spectra of a) P(VSHA50KHE50) copolymer; b)
P(MVSHA50KHE50); c) P(VSHA50MKHE50); d) P(MVSHA50MKHE50)
13
To obtain more detailed information about the structure of the copolyesters C
NMR spectra were obtained. The signals attributable to the ester repeating unit
appear at 173.7 ppm (C=O) and at 63.7 and 63.0 ppm (CH2-OCO). Moreover,
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signals of VSHA unit at 133.1, 131.0, 123.7 and 121.3 ppm (C=C, E and Z
isomers) and those of the KHE at 209.8 ppm (CO) can be seen.
The sensitivity of the 13C NMR to small differences in the chemical environment
enables us to determine the different dyads (AA, AB, BA and BB) structures
(Figure 3). The determination is possible assuming that the methylene carbons
adjacent to the oxygen of the ester function have chemical shifts identical to
those to the corresponding homopolyesters as found for other copolymers.24
These signals appear to split with enough resolution into several peaks between
64.0 and 63.0 ppm due to the different environments occurring along the
polyester chain.
Figure 3. The four possible dyads present in P(VSHAx-KHEy) copolyesters and
13C NMR spectra of the indicated copolyesters with assignments of the peaks to
different carbons.
The number average sequence lengths nA and nB can be calculated as follows:
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nA = 1/ PAB
nB = 1/ PBA
were PAB and PBA are the probability of finding unit B next to unit A and the
probability of finding unit A next to unit B respectively. PAB and PBA can be
calculated by integrating peak areas of the 13C NMR spectrum
PAB= IAB / (IAA + IAB)
PBA = IBA / (IBA + IBB)
where IAA, IAB, IBA and IBB are the peak areas for AA, AB, BA and BB sequences
respectively. The degree of randomness R is defined as:
R = PAB + PBA
For fully random copolymers, R is equal to 1, whereas it is >1 for alternating
and close to 0 for block copolymers. As seen from Table 2 all copolymers
present almost ideal random microstructure with R independent of the
copolymer composition. This suggests that even if there exist differences in
reactivity ratios of the monomers, the copolymers are randomly distributed
because of the rapid transesterification by Novozyme-435.4
Table 2. Microstructure analysis of P(VSHAx-KHEy) copolyesters
Microstructurea
Dyads (mol %)
Number Average
Randomness
Sequence Lengths
Polymer
AA
AB/BA BB
nA
6.7
2.6
1.5
nB
R
P(VSHA80 -KHE20)
P(VSHA50 -KHE50)
P(VSHA20 -KHE80)
74
39
15
25
49
54
1
1.0
1.5
2.2
1.05
1.05
1.10
12
31
a Microstructures were determined statistically by calculation on the basis of the 13C
NMR analysis A: VSHA; B: KHE.
Copolyester Modification
We attempted sequential and single step reactions for modification of
vinylsulfide- ketone-containing copolyesters (Scheme 2). We have examined if
sequential postpolymerization reactions are complicated by the presence of
both moieties and if the analogous one-pot single step reaction yields isolated
14

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polymers with agreement between stoichiometries of the reactants and the
functionalized polymers.
O
HO
S
O
S
O
n
m
O
O
P(VSHAꢁKHE)
HO
Route A
HO
Route B
SH
O
SH
H2N
O
Route C
O
H3N
HO
O
O
O
O
HO
O
S
S
S
O
S
O
n
m
n
m
O
O
S
O
N
O
O
P(VSHAꢁMKHE)
P(MVSHAꢁKHE)
OH
HO
H2N
SH
O
O
O
HO
O
S
S
O
n
m
O
S
N
O
O
OH
P(MVSHAꢁMKHE)
Scheme 2. Sequential and one-pot modifications of P(VSHA50-KHE50)
Sequential post-polymerization modification was first conducted with 2-
mercaptoethanol using a molar ratio 1:1.3 (vinylsulfide/thiol), under UV
irradiation (λ = 365 nm) with 1% of DMPA as photoinitiator in THF solution
leading to P(MVSHA-KHE) (Scheme 2, route A). The course of the reaction
after 30 min was followed by 1H NMR analysis (Figure 2b) by the
disappearance of signals between 5.90 and 5.55 ppm (H3,H4) corresponding to
the double bond in the polymer precursor and the appearance of a new signal
at 3.75 ppm corresponding to CH2OH (H15) of 2-mercaptoethanol moiety linked
to main chain. Moreover, the peak at 2.10 ppm corresponding to methylene
protons linked to double bonds of the precursor dissapears. By 13C NMR, the
disappearance of C=C signals between 133.2 and 121.5 ppm and the
appearance of the new methine signal at 46.2 ppm and the new methylene
signals at 38.6 ppm (CH2-S) and 61.4 ppm (CH2-OH) are observed.
1
After thiol-ene addition, molecular weight from H NMR analysis could not be
determined because of the new signals from mercaptoethanol moiety overlap to
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the end group signals. By SEC analysis the modified polymer had lower
polystyrene equivalent molecular weight with an increase in polydispersity
(Table 3). Thiol-ene modification of main chain 25 or side chain6 has been
reported that occurs without side reactions as degradation or polymer coupling.
By thiol-ene grafting a branched polymer is produced, which makes complex
the comparison of SEC results with the linear precursor and accurate molecular
weight assignments upon thiol-ene grafting are difficult.
Oximes could be easily generated by the coupling reaction between ketones
and oxyamines. The modification of ketone moiety of copolyester
P(VSHA50KHE50)
was
performed
with
O-(tetra-hydro-2H-pyran-2yl)
hydroxylamine at room temperature using a 50% excess of oxyamine relative to
ketone content, to give P(VSHA50MKHE50) (Scheme 4, route B). After 8 h
1
complete conversion of ketone to oxime is observed. Figure 2c shows the H
NMR spectrum of the copolymer with the new proton resonances at 5.20 ppm
(H16), 3.85 ppm and 3.60 ppm (H17) attributed to the tetrahydropyranyl moiety.
The methine proton linked to sulfur atom (H9) was also detected with
resonances appearing at 3.10 ppm and 2.91 ppm. Moreover, 13C NMR
spectrum shows signals attributable to the oxyamine moiety at 100.6 and 62.8
ppm along with the disappearance of ketone carbonyl signal at 209.1 ppm and
the appearance of the new signal at 160.6 ppm of the oxime bond.
Next, the modification of ketone moiety of P(MVSHA50-KHE50) (Scheme 4, route
A) with O-(tetra-hydro-2H-pyran-2yl) hydroxylamine was performed using the
above mentioned conditions. After 8 h complete conversion of ketone to oxime
1
is observed obtaining P(MVSHA50-MKHE50). Figure 2d shows the H NMR
spectrum of the copolymer with the new proton resonances at 5.20 ppm (H16),
3.85 ppm and 3.60 ppm (H17) attributed to the tetrahydropyranyl moiety. The
methine proton linked to sulfur atom (H9) was also detected with resonances
appearing at 3.10 ppm and 2.91 ppm, confirmed by spectroscopic analysis, 2-D
NMR gHSQC (Figure 4).
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Figure 4. 2-D NMR gHSQC spectrum of P(MVSHA50MKHE50)
Likewise, the modification of P(VSHA50-MKHE50) with 2-mercaptoethanol
(Scheme 4, route B) was carried out leading to P(MVSHA50-MKHE50). Similar
results as sequential modification route A, were obtained.
To explore the utility of acid-catalyzed oxime formation, the reaction was also
carried out by using p-toluenesulfonic acid. In this case, and using 1:1 molar
ratio ketone/oxyamine, complete reaction took place in 5 h and without
significant variations on molecular weights after this second modification were
observed by SEC (Table 3). Thus, although the copolymer was produced
through an acidic reaction, no significant degradation of the polyester backbone
was observed. Sequential reactions were performed in the opposite order of
addition to generate first the ketoxime and followed by the thioether formation.
Using the acid catalyzed reaction and the same reaction conditions in both
steps as above described, similar results were obtained.
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Table 3. Molecular weights of copolyesters
Polymer
Mna
15532
9022
9037
Mw
PDI
1.74
2.25
2.19
(2.17)
1.66
1.55
1.65
P(VSHA50KHE50)
P(MVSHA50KHE50)
P(MVSHA50MKHE50)b
27142
20330
19791
(9219)d (20032)
P(VSHA50MKHE50)
P(MVSHA50MKHE50)b
P(MVSHA50MKHE50)c
15754
8170
4153
26226
12725
6873
a SEC values were obtained using THF as solvent.
b Copolyester obtained by sequential modification.
c Copolyester obtained by one pot modification.
d
In brackets values when acid catalyst was used.
Additionally, we explored the one pot functionalization to achieve the single-step
preparation of the bifunctionalized copolyester. Reaction was carried out by
adding 2-mercaptoethanol and O-(tetra-hydro-2H-pyran-2yl) hydroxylamine and
UV irradiating for 30 min. After 8 h of reaction, lower modification degrees than
those obtained by sequential addition were obtained (92% for thioether and
67% for ketoxime formations). Lower molecular weights than those obtained by
sequential modificacion were also observed (Table 3).
Thermal properties
The thermal behavior of copolyesters has been comparatively studied by DSC
and TGA in nitrogen atmosphere taking as reference their parent
homopolyesters from VSHA and KHE (Table 4). Data for the parent
homopolymers are also included for comparison. PVSHA showed a melting
endotherm centered at 19 ºC with a melting enthalphy of 38 J/g according to its
crystalline nature, while PKHE showed the glass transition at -60 ºC according
to its amorphous character. Thermal stability of PVSHA is significantly higher
than the one of PKHE. Although a common pattern of degradation is followed
by all of the unmodified copolymers, initial degradation temperatures show the
influence of the composition, and the higher the amount of VSHA, the higher the
thermal stability. However, the modified copolyester show a noticeable
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decrease on thermal stability and the appearance of a new degradation step. A
decrease on the thermal stability of the oxime modified copolymer was
previously described.20
Table 4. DSC and TGA properties of the polymers
Polymer
PVSHA
Tg(ºC)
-54
Tm (ºC)
T5% (ºC)a
337
Tmaxb
354-451
R (%)c
2.5
19 (38J/g)
PKHE
-60
-
256
349-447
0.5
P(VSHA80-KHE20)
P(VSHA50-KHE50)
P(VSHA20-KHE80)
P(MVHA50MKHE50)
-57
-7 (12J/g)
315
349-448
0.4
-57
-
-
-
296
347-449
0.7
-61
282
343-447
0.3
-46
226
268-338-448
2.5
a Temperature corresponding the 5% weight loss
b Temperatures corresponding to the maximum weight loss rate
c Remaining weight at 800 ºC
Conclusion
Copolymers carrying both vinyl sulfide and ketone functional groups have been
obtained by enzymatic polymerization. Sequential and single step one pot post-
polymerization modifications of both functional groups have been carried out.
Sequential modification yields materials with good agreement between the
reaction stoichiometry and the observed incorporation of thiol and oxyamine,
and the order of addition seems not to be a significant parameter. One pot
functionalization strategy allows for the single step modification but not
quantitative either thiol-ene or oxime reaction were achieved. In spite of the
differences in molecular weights obtained by SEC, no significant degradation
seems to take place as observed by NMR spectroscopy since no unexpected
signals can be observed.
ACKNOWLEDGEMENTS
Financial support by the MINECO (Ministerio de Economia e Innovación,
MAT2014-53652-R) is gratefully acknowledged.
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Synthesis and functionalization of vinylsulfide and ketone-containing
aliphatic copolyesters from fatty acids
Zeynep Beyazkilic, Gerard Lligadas, Juan Carlos Ronda, Marina Galià,
Virginia Cádiz
Departament de Química Analítica i Química Orgànica, Universitat Rovira i
Virgili, C/Marcel.lí Domingo 1, 43007 Tarragona, Spain
Correspondence to: Author Name (e-mail:marina.galia@urv.cat)
HIGHLIGHTS
•
•
A series of novel aliphatic copolyesters bearing vinylsulfide and ketone
functional groups were obtained
Sequential and single step one pot post-polymerization modifications of
both functional groups were carried out
1