In-chain poly(phosphonate)s via acyclic diene metathesis polycondensation

Article abstract of DOI:10.1021/acs.macromol.6b00366

In-chain poly(phosphonate)s have been prepared via acyclic diene metathesis polymerization of three different monomers. Novel unsaturated phosphonate monomers with asymmetric structure have been developed. The monomers are accessible via a three-step synthesis that can be easily scaled up. This is the first report on poly(phosphonate)s by olefin metathesis where the stable carbon-phosphorus linkage is localized in the polymer backbone. This changes the nature of the degradation products compared to other poly(phosphoester)s. Polymers with molecular weights up to 31000 g mol^-1 can be achieved and have been characterized in detail NMR spectroscopy, size exclusion chromatography, thermogravimetry, and differential scanning calorimetry. They have been also compared to structural analogues polyphosphates with respect to crystallization (SAXS, WAXS) and their rheological behavior. Also, solution grown crystals were analyzed rendering some of the herein reported poly(phosphonate)s as interesting defect poly(ethylene)-like structures.

Full text of DOI:10.1021/acs.macromol.6b00366

Article
pubs.acs.org/Macromolecules
In-Chain Poly(phosphonate)s via Acyclic Diene Metathesis
Polycondensation
Kristin N. Bauer, Hisaschi T. Tee, Ingo Lieberwirth, and Frederik R. Wurm*
Max-Planck-Institut fur Polymerforschung, Ackermannweg 10, 55128 Mainz, Germany
̈
S
* Supporting Information
ABSTRACT: In-chain poly(phosphonate)s have been prepared via acyclic
diene metathesis polymerization of three different monomers. Novel
unsaturated phosphonate monomers with asymmetric structure have been
developed. The monomers are accessible via a three-step synthesis that can
be easily scaled up. This is the first report on poly(phosphonate)s by olefin
metathesis where the stable carbon−phosphorus linkage is localized in the
polymer backbone. This changes the nature of the degradation products
compared to other poly(phosphoester)s. Polymers with molecular weights
up to 31 000 g mol−1 can be achieved and have been characterized in detail
NMR spectroscopy, size exclusion chromatography, thermogravimetry, and
differential scanning calorimetry. They have been also compared to
structural analogues polyphosphates with respect to crystallization (SAXS, WAXS) and their rheological behavior. Also, solution
grown crystals were analyzed rendering some of the herein reported poly(phosphonate)s as interesting defect poly(ethylene)-like
structures.
handle for adjusting the degradation profile.8 Under physio-
logical conditions PPEs can be degraded due to the
hydrolytically and enzymatically degradable phosphoester
INTRODUCTION
■
Degradable polymersnatural or synthetichave become a
major research area in polymer science, ranging from everyday
bonds along the polymer backbone into phosphates, diols,
plastics to complex nanostructures.1 Polymers with a merely
and alcohols as the final breakdown products.3a PPEs are
carbon-based backbone are resilient against environmental
influences (hydrolysis, enzymes, most UV light) and typically
known since the 1930s, but compared to conventional
polyesters, the interest in these polymers faded because of
the expensive synthesis and low molecular weights combined
with mostly ill-defined structures. However, since the 1970s
do not degrade in vivo and in many cases show long half-life
times also in the natural environment.2 In contrast, polymers
with heteroatoms in the backbone, such as polyesters,
polyamides, polyanhydrides, polyurethanes, and polyureas,
show a strong structure−degradation relation depending on
PPEs have been studied sporadically in academia mainly based
on the pioneering works of Penczek;9 later the groups of
Wang,10 Leong,11 and Iwasaki12 have paved the way to PPEs
with control over structure and molecular weights. Typical
approaches to PPEs are first and foremost the polycondensa-
tion of phosphorus dichlorides or diesters with diols,13 the
polyaddition,14 and the ring-opening polymerization of cyclic
phosphorus compounds.15 During the past few years the acyclic
diene metathesis (ADMET) polymerization has proven to be a
reliable method for the preparation of (unsaturated) PPEs
((U)PPEs) with diverse thermal properties due to the precise
adjustability of main and side chains.16
the conditions, e.g., hydrolysis and/or enzymatic cleavage.3
During the past decades degradable polymers have attracted
tremendous interest for the development of therapeutic devices
such as temporary prostheses,4 porous structures as scaffolds
for tissue engineering,5 or as vehicles for sustained drug
release.6 Each of these applications demands high standards
concerning physical, chemical, biochemical, and degradation
properties to guarantee efficient therapy. Besides the
biodegradability, especially the biocompatibility of the polymer
and the degradation products is crucial for the usage of a
polymeric material in the biomedical field. One class of
biodegradable polymers which is especially appealing for the
application in the biomedical field are main-chain poly-
(phosphoester)s (PPEs) not only due to their similarity to
biomacromolecules such as the most prominent PPE,
deoxyribose nucleic acid (DNA), but also due to their high
structural and chemical versatility.7 The pentavalency of
phosphorus enablesin contrast to carboxylic polyesters
the introduction of pendant functional and/or solubilizing
groups in every repeat unit and at the same time is a direct
Furthermore, the high functional group tolerance of the
ruthenium catalysts allows the synthesis of polymers with
functional groups.17 However, the usage of these materials in
biomedical applications is still limited due to the hydrophobic
long-chain diols, which are part of the final degradation
products of the PPEs and reduce the degradation kinetics. To
Received: February 19, 2016
Revised: April 20, 2016
© XXXX American Chemical Society
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column, a UV (Spectra System UV 2000), and a refractive index
(RI) detector (Agilent Technologies 1260 Infinity). Calibration was
carried out using polystyrene standards provided by Polymer
Standards Service. For the poly(phosphate) SEC measurements
were performed in THF with a PSS SecCurity system (Agilent
Technologies 1260 Infinity). Sample injection was performed by a
1260-ALS autosampler (Waters) at 30 °C. SDV columns (PSS) with
dimensions of 300 × 80 mm, 10 μm particle size, and pore sizes of
106, 104, and 500 Å were employed. The DRI Shodex RI-101 detector
(ERC) and UV−vis 1260-VWD detector (Agilent) were used for
detection. Calibration was achieved using poly(styrene) standards
provided by Polymer Standards Service. For nuclear magnetic
date, the ADMET protocol was used to prepare poly-
(phosphate)s16a,18 and main-chain poly(phosphonates)s with
the stable P−C bond as side chain (cf. Figure 1).19
1
resonance analysis H, 13C, and 31P NMR spectra of the monomers
were recorded on a Bruker AVANCE III 300, 500 or 700 MHz
spectrometer. All spectra were measured in either CD2Cl2 or CDCl3 at
298 K. The spectra were calibrated against the solvent signal and
analyzed using MestReNova 8 from Mestrelab Research S.L. The
thermal properties of the synthesized polymers have been measured by
differential scanning calorimetry (DSC) on a Mettler Toledo DSC 823
calorimeter. Three scanning cycles of heating−cooling were performed
in a N2 atmosphere (30 mL/min) with a heating and cooling rate of 10
°C/min. TGA was measured on a Mettler Toledo ThermoSTAR
TGA/SDTA 851-Thermowaage in a nitrogen atmosphere. The
heating rate was 10 °C/min in a range of temperature between 25
and 600−900 °C. Vapor pressure osmometry (VPO) was measured on
a Knaur vapor pressure osmometer K-7000 in chloroform at 30 °C.
Calibration was carried out using poly(ethylene glycol) methyl ether.
Dynamic mechanical analysis (DMA) was performed using an
Advanced Rheometric Expansion System (ARES) equipped with a
force-rebalanced transducer. Plate−plate geometry was used with plate
diameters of 6 mm. The gap between plates was around 1 mm.
Experiments were performed under dry nitrogen atmosphere. The
isochronal temperature dependencies of G′ and G″ were determined
for ω = 10 rad/s. For wide-angle X-ray scattering (WAXS) and small-
angle X-ray scattering (SAXS) experiments the sample was prepared
by hot pressing an approximately 200−400 μm thick film on a hot
stage. In order to achieve a well-crystallized specimen, we prepared an
annealed sample by heating the sample well above the melting point to
120 °C and kept it at this temperature for 10 min. Subsequently, it was
cooled from the melt to 42 °C and kept at this temperature for 48 h.
SAXS was recorded using Cu Kα radiation (wavelength 1.54 Å) from a
rotating anode source (Rigaku MicroMax 007 X-ray generator) with
curved multilayer optics (Osmic Confocal Max-Flux). Polymer foils
were measured in transmission geometry. The scattered intensity was
recorded on a 2D detector (Mar345 image plate) with a sample−
detector distance of 2 m. For WAXS measurements the sample−
detector distance was set to 20 cm. For TEM examination solution
grown crystals were prepared from a 0.05% solution in n-octane. The
solution was heated to 85 °C in a temperature-controlled oil bath and
slowly cooled down to room temperature to achieve a turbid
dispersion. One drop of this dispersion was applied to a carbon-
coated TEM grid, excess liquid was blotted of with a filter paper, and
the specimen was allowed to dry under ambient conditions. A FEI
Tecnai F20 transmission electron microscope operated at an
acceleration voltage of 200 kV was used to determine the crystal
morphology, thickness, and crystal structure. Bright field (BF) and
energy-filtered transmission electron microscopy (EFTEM) techni-
ques were used for measurements.
Figure 1. Structure of poly(phosphate)s (left) and main-chain
poly(phosphonate)s with the P−C bond as pendant group (middle)
or as part of the PPE backbone (right).
Poly(phosphonate)s are an almost forgotten subclass of
PPEs, consisting of two ester linkages and one alkyl or aryl
group, which is directly attached to the phosphorus atom. The
degradation profiles of poly(phosphonate)s and poly-
(phosphate)s differ due to the stable P−C bonds; however,
for both systems hydrolytic and enzymatic cleavage has been
reported. In the so far reported main-chain poly(phosphonate)s
the two phosphoesters build up the polymer backbone, while
the P−C bond is the pendant group.20 Especially aliphatic
poly(phosphonate)s are interesting materials for usage in the
biomedical field, since they are potentially biodegradable and
biocompatible. Nevertheless, besides some recently published
approaches to aliphatic phosphonates,15b,21 to date, mainly
aromatic poly(phosphonate)s are known for their flame-
retardant properties.
Herein, we describe the first synthesis of main-chain
poly(phosphonate)s by ADMET polycondensation with the
P−C bond as a part of the polymer backbone (“in-chain”,
Figure 1, right) and compare them to structural analogue
poly(phosphate)s. Different monomers and polymers have
been prepared with varying the hydrophilicity and the
phosphorus content. The monomer syntheses were performed
in three to four steps yielding difunctional phosphonates with
the polymerizable double bond in the stable phosphonate
chain. The polycondensation was conducted in bulk or in
solution leading to a quantitative polymer formation. This new
class of (U)PPEs allows the reduction of the hydrophobic
degradation products to a minimum: by “rotating” the P−C
bond from the pendant chain into the polymer backbone, the
degradation product remains attached to the charged
phosphonates and thus should allow their easy body clearance.
Synthesis of 6-Iodohex-1-ene. This compound was synthesized by
a literature procedure22 from hex-5-en-1-ol (20.48 mL, 17 g, 169.73
mol) with triphenylphosphine (53.42 g, 203.7 mmol), imidazole
(13.87 g, 203.7 mmol), and iodine (51.7 g, 203.7 mmol) in
dichloromethane to yield after distillation 6-iodohex-1-ene as a
EXPERIMENTAL SECTION
■
Materials. Solvents and chemicals were purchased from Acros
Organics, Sigma-Aldrich, or Fluka and used as received, unless
otherwise stated. Triethyl phosphite was used as received from Sigma-
Aldrich. Deuterated solvents were purchased from Sigma-Aldrich and
kept over molecular sieves.
1
colorless oil (29.3 g, 82%). H NMR (250 MHz, chloroform-d): δ
5.72 (ddt, J = 16.9, 10.2, 6.7 Hz, 1H), 5.02−4.84 (m, 2H), 3.12 (t, J =
7.0 Hz, 2H), 2.10−1.93 (m, 2H), 1.86−1.69 (m, 2H), 1.52−1.36 (m,
2H).
Synthesis of 11-Iodoundec-1-ene. This compound was synthesized
according to a literature procedure.23 11-Bromoundec-1-ene (10 g,
42.9 mmol) was treated with NaI (12.86 g, 85.8 mmol) in 50 mL of
Instrumentation and Characterization Techniques. For the
poly(phosphonate)s size exclusion chromatography (SEC) measure-
ments were performed in THF with an Agilent 1100 Series as an
integrated instrument, including a MZ-Gel SD plus e5/e3/100
B
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acetone under reflux over 16 h. Acetone was removed under reduced
pressure, and water was added to the residue. The mixture was
extracted with diethyl ether, and the combined organic layers were
dried with sodium sulfate and concentrated under reduced pressure to
yield known 11-iodoundec-1-ene as slight yellow oil (11.35 g, 94%).
1H NMR (300 MHz, chloroform-d): δ 5.74 (ddt, J = 16.9, 10.1, 6.7
61.42, 53.41, 33.17, 29.97, 29.94, 29.88, 29.79, 29.69, 25.87, 25.07,
24.80, 21.92, 21.89, 16.50, 16.46. 31P{H} NMR (283 MHz,
chloroform-d): δ 32.36. (3) H NMR (700 MHz, chloroform-d): δ
1
5.82 (ddd, J = 16.8, 10.4, 5.3 Hz, 2H), 4.98 (dd, J = 43.4, 13.6 Hz, 4H),
4.07 (dddd, J = 59.0, 28.2, 15.3, 7.9 Hz, 4H), 2.06 (q, J = 7.5, 7.1 Hz,
4H), 1.68 (ddq, J = 57.5, 43.3, 8.6, 7.7 Hz, 7H), 1.44−1.21 (m, 29H).
13C NMR (176 MHz, chloroform-d): δ 139.13, 114.11, 65.44, 65.40,
61.38, 61.34, 33.77, 30.63, 30.58, 30.54, 29.44, 29.39, 29.37, 29.30,
29.14, 29.07, 28.89, 28.71, 26.01, 25.52, 25.21, 22.41, 22.38, 16.50,
16.46. 31P{H} NMR (283 MHz, chloroform-d): δ 32.62. (4) 1H NMR
(700 MHz, chloroform-d): δ 5.85−5.73 (m, 2H), 5.03−4.89 (m, 4H),
4.14−3.93 (m, 5H), 2.07 (q, J = 7.2, 6.7 Hz, 2H), 2.05−2.00 (m, 3H),
1.74−1.64 (m, 4H), 1.61−1.54 (m, 2H), 1.49−1.44 (m, 2H), 1.35 (qd,
J = 7.0, 3.5 Hz, 4H), 1.30 (td, J = 7.1, 1.3 Hz, 3H), 1.29−1.23 (m, 8H).
13C NMR (176 MHz, chloroform-d): δ 139.17, 138.30, 114.83, 114.12,
65.19, 65.15, 61.42, 61.39, 60.37, 33.79, 33.19, 30.64, 30.55, 29.40,
28.90, 26.03, 25.23, 24.82, 22.43, 22.40, 16.52, 16.49, 14.19. 31P{H}
NMR (283 MHz, chloroform-d): δ 32.66.
Hz, 1H), 5.02−4.82 (m, 2H), 3.12 (td, J = 7.0, 2.9 Hz, 2H), 2.06−1.91
(m, 2H), 1.75 (p, J = 7.1 Hz, 2H), 1.27 (d, J = 30.4 Hz, 12H).
General Procedure for the Synthesis of Diethyl Alkyl Phospho-
nates. The diethyl alkyl phosphonates were synthesized by a
Michaelis−Arbuzov reaction of the corresponding alkyl halides with
triethyl phosphite. For the synthesis of diethyl but-3-en-1-ylphosph-
onate (1′) 4-bromobut-1-ene was used whereas 6-iodohex-1-ene and
11-iodoundec-1-ene were used as alkyl halides for the syntheses of
diethyl hex-5-en-1-ylphosphonate (2′) and diethyl undec-10-en-1-
ylphosphonate (3′). A mixture of the alkyl halide (1 equiv) and triethyl
phosphate was heated up to 100−140 °C until the alkyl halide was
consumed completely (the consumption of the alkyl halide was
monitored by NMR measurements since no solvent is used for the
reaction). The diethyl alkyl phosphonates are obtained in 75−85%
Synthesis of Bis(undec-10-en-1-yl) Ethylphosphate (5). A Schlenk
flask, equipped with a dropping funnel, was charged with ethyl
dichlorophosphate (1 equiv), dissolved in dry CH2Cl2 (1.9 mol/L)
under an argon atmosphere. The solution was cooled to 0 °C with an
ice bath. DMAP (0.01 equiv), Et3N (1.8 equiv), and 10-undecen-1-ol
(1.8 equiv) were dissolved in dry CH2Cl2 (10 mol/L) and dropped
over a period of 1 h via the dropping funnel. After the addition the
reaction was stirred overnight at room temperature. The crude mixture
was concentrated at reduced pressure, dissolved in diethyl ether, and
filtered. The organic phase was washed twice with 10% aqueous
hydrochloric acid solution and twice with brine. The organic layer was
dried over sodium sulfate, filtered, concentrated at reduced pressure,
and purified by flash chromatography over neutral alumina using
1
yield. (1′) H NMR (300 MHz, chloroform-d): δ 5.79 (ddt, J = 16.6,
10.1, 6.3 Hz, 1H), 5.07−4.89 (m, 2H), 4.10−3.99 (m, 4H), 2.28 (ddtt,
J = 11.1, 9.4, 6.4, 1.5 Hz, 2H), 1.85−1.67 (m, 2H), 1.31−1.24 (m,
1
6H). (2′) H NMR (300 MHz, chloroform-d): δ 5.72 (ddt, J = 16.9,
10.1, 6.6 Hz, 1H), 4.99−4.85 (m, 2H), 4.02 (dqd, J = 7.7, 7.1, 3.5 Hz,
4H), 2.07−1.94 (m, 2H), 1.73−1.47 (m, 4H), 1.47−1.35 (m, 2H),
1
1.25 (t, J = 7.1 Hz, 6H). (3′) H NMR (250 MHz, chloroform-d): δ
5.74 (ddt, J = 16.9, 10.2, 6.7 Hz, 1H), 5.01−4.79 (m, 2H), 4.17−3.87
(m, 4H), 1.96 (qt, J = 6.6, 1.4 Hz, 2H), 1.75−1.41 (m, 4H), 1.25 (t, J =
7.1 Hz, 18H).
General Procedure for the Synthesis of Ethyl Hydrogen
Alkenylphosphonates. The compounds were synthesized according
to the literature.24 Briefly, a solution of the diethyl alkenylphosphonate
(1 equiv) was treated dropwise with trimethylsilyl bromide (1.2 equiv)
at room temperature. After stirring for a further hour at room
temperature, the reaction was quenched with 5% KHSO4 solution and
stirred vigorously for 5 min. The phases were separated, and the water
phase was washed with ethyl acetate. The organic layers were
combined and dried with sodium sulfate. After removal of the solvent
under reduced pressure the crude ethyl hydrogen alkenylphosphonates
1
dichloromethane as eluent to give a clear yellowish liquid. H NMR
(300 MHz, chloroform-d): δ 5.79 (ddt, J1 = 15 Hz, J2 = 9 Hz, J3 = 6
Hz, 2H), 4.97 (ddt, J1 = 17.1 Hz, J2 = 3.6 Hz, J3 = 1.5 Hz, 2H), δ 4.91
(ddt, J1 = 9.9 Hz, J2 = 2.1 Hz, J3 = 1.2 Hz, 2H), δ 4.14−4.04 (m, 2H), δ
4.01 (td, J1 = 9 Hz, J2 = 4.5 Hz, 4H), δ 2,06−1.98 (m, 4H), δ 1.70−
1.63 (m, 4H), δ 1.38−1.27 (m, 24H).
General Procedure for the ADMET Bulk Polymerization. In a glass
Schlenk tube the respective monomer (1 equiv) and the Grubbs
catalyst first generation (0.03 equiv) were combined under an argon
atmosphere. Polymerization was carried out at reduced pressure (to
remove the ethylene gas evolving during the metathesis polymer-
ization) at 60 °C for 24 h. The polymers are obtained as brown viscous
materials in quantitative yield.
1
were obtained and used without further purification. (1″) H NMR
(300 MHz, chloroform-d): δ 10.25 (s, 1H), 5.89−5.64 (m, 1H), 5.15−
4.84 (m, 2H), 4.16−3.91 (m, 2H), 2.43−2.18 (m, 2H), 1.86−1.70 (m,
2H), 1.27 (td, J = 7.1, 2.0 Hz, 3H). (2″) 1H NMR (300 MHz,
chloroform-d): δ 9.93 (s, 1H), 5.72 (ddt, J = 16.9, 10.2, 6.7 Hz, 1H),
5.03−4.81 (m, 2H), 4.17−3.91 (m, 2H), 2.00 (q, J = 7.1 Hz, 2H),
1.80−1.33 (m, 6H), 1.26 (td, J = 7.1, 1.3 Hz, 3H). (3″) 1H NMR (250
MHz, chloroform-d): δ 7.61 (s, 1H), 7.20 (s, 1H), 5.75 (ddt, J = 16.9,
10.1, 6.7 Hz, 2H), 5.01−4.74 (m, 2H), 4.14−3.91 (m, 2H), 2.04−1.87
(m, 4H), 1.45−1.09 (m, 15H).
General Procedure for the ADMET Solution Polymerization. In a
glass Schlenk tube the respective monomer (1 equiv) and the Grubbs
catalyst first generation (0.03−0.06 equiv) were dissolved in 1-
chloronaphthalene under an argon atmosphere. Polymerization was
carried out at reduced pressure (to remove the ethylene gas evolving
during the metathesis polymerization) at 60 °C for 24−48 h. To
remove 1-chloronaphthalene the obtained polymers were precipitated
three times into hexane. The polymers are obtained as brown viscous
materials in quantitative yield. Poly(2). 1H NMR (500 MHz,
chloroform-d): δ 5.46−5.31 (m), 4.17−3.91 (m), 2.13−1.93 (m),
1.68 (dtd, J = 33.7, 18.7, 17.4, 10.5 Hz), 1.44 (qd, J = 7.6, 3.5 Hz), 1.32
(t, J = 7.0 Hz). 13C NMR (126 MHz, methylene chloride-d2): δ 75.37,
75.11, 74.86, 63.37, 63.32, 59.56, 59.51, 30.10, 28.66, 28.53, 28.25,
28.15, 28.10, 24.80, 24.11, 23.69, 23.53, 23.52, 22.99, 20.22, 20.08,
General Procedure for the Synthesis of In-Chain Phosphonate
ADMET Monomers. The respective hydrogen alkenylphosphonate (1
equiv) was mixed with Cs2CO3 (1.1 equiv) in DMF at room
temperature. After stirring for 30 min the alkenyl iodide was added
dropwise, and the reaction mixture was allowed to react for 12 h. The
reaction mixture was filtrated, and the filtration residue was washed
thrice with DMF. The filtrate was concentrated under reduced
pressure, and the crude product was purified by column chromatog-
raphy over silica using ethyl acetate/petroleum ether as eluent. The
ADMET monomers are obtained in 30−40% yield. (1) 1H NMR (500
MHz, chloroform-d): δ 5.87−5.70 (m, 2H), 5.14−4.92 (m, 4H),
4.14−3.97 (m, 4H), 2.39 (qt, J = 6.7, 1.4 Hz, 2H), 2.31 (ddtt, J = 11.3,
9.5, 6.5, 1.5 Hz, 2H), 1.79 (ddt, J = 20.0, 11.7, 4.4 Hz, 2H), 1.29 (t, J =
7.1 Hz, 3H). 13C NMR (126 MHz, chloroform-d): δ 137.18, 133.60,
117.55, 115.10, 77.26, 64.54, 61.56, 34.95, 26.49, 25.54, 24.42, 16.44.
1
20.04. 31P{H} NMR (202 MHz, chloroform-d): δ 32.38. Poly(3). H
NMR (500 MHz, chloroform-d): δ 5.43−5.34 (m), 4.19−3.95 (m),
2.07−1.94 (m), 1.80−1.55 (m), 1.43−1.26 (m). 13C NMR (126 MHz,
chloroform-d): δ 65.31, 65.26, 61.42, 61.37, 32.62, 32.60, 32.03, 30.71,
30.58, 30.05, 29.67, 29.62, 29.51, 29.47, 29.39, 29.20, 29.18, 29.13,
28.50, 26.18, 25.50, 25.46, 25.07, 22.45, 22.41. 31P{H} NMR (202
MHz, chloroform-d): δ 32.59. Poly(4). 1H NMR (500 MHz,
chloroform-d): δ 5.46−5.29 (m), 4.17−3.93 (m), 2.01 (tdd, J =
25.3, 13.3, 6.7 Hz), 1.82−1.53 (m), 1.43 (dt, J = 10.0, 6.6 Hz), 1.40−
1.23 (m). 13C NMR (126 MHz, methylene chloride-d2): δ 75.40,
75.15, 74.89, 63.54, 63.48, 59.46, 59.41, 30.68, 30.28, 30.13, 28.76,
28.69, 28.64, 27.84, 27.80, 27.73, 27.57, 27.53, 27.50, 27.44, 27.36,
1
31P{H} NMR (202 MHz, chloroform-d) δ 31.59. (2) H NMR (500
MHz, chloroform-d): δ 5.78−5.67 (m, 2H), 4.99−4.86 (m, 4H),
4.10−3.88 (m, 4H), 2.06−1.94 (m, 5H), 1.71−1.49 (m, 6H), 1.41 (p, J
= 7.5 Hz, 4H), 1.25 (t, J = 7.0 Hz, 3H). 13C NMR (176 MHz,
chloroform-d): δ 138.27, 138.18, 114.82, 114.80, 65.21, 65.17, 61.45,
C
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Scheme 1. (a) Synthesis of In-Chain Phosphonate Monomers; (b) ADMET Polycondensation of Monomers 1−4 and
Subsequent Hydrogenation
27.26, 27.24, 27.18, 26.91, 26.25, 25.29, 25.04, 24.39, 24.25, 23.77,
23.62, 23.13, 20.51, 20.47. 31P{H} NMR (202 MHz, methylene
chloride-d2): δ 30.74 (d, J = 4.4 Hz).
iodide was applied to install the terminal double bond for olefin
metathesis at the phosphorus center (Scheme 1, synthesis of 1′,
2′, and 3′). The usage of either the alkenyl bromide or iodide is
dependent on the reactivity: for the synthesis of the “short”-
chain phosphonates, i.e. 1′, the bromide is sufficient, while for
the synthesis of the derivatives with longer alkyl chain (2′ and
3′), the more reactive iodides were necessary. The alkenyl
halides are commercially available or can be synthesized by the
reaction of the corresponding alcohol with imidazole and
iodine according to the literature.22,23 After the formation of
the diethylalkenyl phosphonates (1′, 2′, and 3′), one
phosphoester was cleaved with trimethylsilyl bromide. The
final difunctional monomer was then prepared by the
esterfication of the crude precursor hydrogen alkenyl
phosphonate with an alkenyl halide of choice using Cs2CO3
in DMF (Scheme 1).
This protocol allows the synthesis of symmetrical and
unsymmetrical phosphonates monomers, which was also not
reported for the respective phosphates. The monomers were
purified by column chromatography as colorless liquids in
moderate yields (compare Experimental Section). For compar-
ison, bis(undec-10-en-1-yl) ethylphosphate (5), a so far not
reported ADMET monomer, was prepared in high yields from
ethyl dichlorophosphate and undecenol. All monomers were
stable at room temperature at least for several months. This
general protocol allows the variation of the phosphorus content
and thus the hydrophilicity of the materials easily. The pendant
group could be varied by changing from triethyl phosphite to
other precursors. Spectral characterization of all monomers is
listed in the Supporting Information Figures S1−S12.
General Procedure for the Catalytic Hydrogenation of ADMET
Polymers. The polymers Poly(2), Poly(3), and Poly(4) were charged
into a Schlenk flask and dissolved in toluene (ca. 12 wt %). To remove
the disturbing oxygen, the flask was evacuated and flushed with argon
again. 10 wt % of 5% Pd/C catalyst were added followed by the
removal of argon under reduced pressure and flushing with hydrogen.
Hydrogen was bubbled into the solution via a septum and syringe.
Hydrogenation was then performed with a hydrogen balloon under
vigorous stirring at room temperature until NMR showed no signals of
double bonds. The solution was filtered over Celite, and the solid
polymer was isolated after removal of the solvent in quantitative yield.
Poly(2)-H. 1H NMR (500 MHz, chloroform-d): δ 4.03 (ddt, J = 38.3,
13.6, 7.4 Hz), 2.10 (s), 1.65 (ddq, J = 39.1, 32.3, 8.1 Hz), 1.33 (ddt, J =
28.9, 14.8, 6.1 Hz). 13C NMR (126 MHz, chloroform-d): δ 77.20,
65.47, 65.42, 61.42, 61.37, 30.69, 30.63, 30.59, 30.56, 30.54, 29.69,
29.51, 29.47, 29.45, 29.33, 29.28, 29.17, 29.09, 28.90, 26.22, 25.54,
25.52, 25.10, 22.45, 22.41, 16.53, 16.49. 31P{H} NMR (202 MHz,
1
chloroform-d): δ 32.12. Poly(3)-H. H NMR (500 MHz, methylene
chloride-d2): δ 4.03−3.82 (m), 1.58 (dddd, J = 21.5, 14.8, 11.8, 7.0
Hz), 1.47 (ddt, J = 15.7, 11.2, 7.2 Hz), 1.32−1.13 (m). 13C NMR (126
MHz, methylene chloride-d2): δ 65.31, 65.26, 61.26, 61.21, 53.84,
53.63, 53.41, 53.19, 52.98, 30.62, 30.57, 30.52, 29.72, 29.71, 29.68,
29.63, 29.60, 29.55, 29.42, 29.20, 29.12, 26.01, 25.57, 24.90, 22.44,
22.40. 31P{H} NMR (202 MHz, methylene chloride-d2): δ 32.12.
Poly(4)-H. 1H NMR (500 MHz, methylene chloride-d2): δ 4.03−3.81
(m), 1.67−1.41 (m), 1.36−1.10 (m). 13C NMR (126 MHz, methylene
chloride-d2): δ 65.47, 61.47, 61.42, 54.00, 53.78, 53.57, 53.35, 53.14,
30.78, 30.73, 30.68, 29.88, 29.83, 29.79, 29.76, 29.71, 29.61, 29.59,
29.36, 29.33, 29.28, 26.16, 25.72, 25.05, 22.59, 22.55. 31P{H} NMR
(202 MHz, methylene chloride-d2): δ 32.19.
ADMET Polycondensation. The polycondensation reac-
tions of the monomers 1−4 were carried out according to the
conditions developed by our group recently18 for the
polymerization of the phosphates and phosphonates. The
monomers 1−4 have been polymerized in a ruthenium-
catalyzed acyclic diene metathesis reaction at reduced pressure
at 60 °C using the Grubbs catalyst first generation. Variation of
molecular weights was achieved by conducting the reaction in
the high boiling solvent 1-chloronaphthalene (20 wt %) to
guarantee continuous mixing during the polymerization
process. The obtained polymers poly(1)−(4) are viscous
RESULTS AND DISCUSSION
■
Monomer Synthesis. To date, difunctional or trifunctional
phosphate or phosphonates monomers with different chain
lengths were accessible via esterification of terminal unsaturated
alcohols with phosphoryl chloride or derivatives.18,25 In
contrast, the protocol for the corresponding phosphonate
monomers for the synthesis of in-chain poly(phosphonate)s
needed to be designed. To generate a phosphonate monomer
suitable for ADMET polymerization, the Michaelis−Arbuzov
reaction between triethyl phosphite and an alkenyl bromide or
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materials with molecular weights up to 2.1 × 104 g mol−1 and
molecular weight dispersities of Đ ≈ 2 for poly(3) and poly(4),
which are in good agreement with the theoretically predicted
distribution by the Carothers equation (compare Table S1).
Poly(2) could not be analyzed by SEC due to strong
interactions with the column material (different conditions
were tested, but in all cases no elution was detected). As the
successful polymerization of 2 was proven by NMR spectros-
copy, this is an interesting finding and distinct difference to the
analogues phosphate, which eluted under the same conditions
from the SEC column. Vapor pressure osmometry let us at least
estimate a molecular weight of ca. 8000 g mol−1 for poly(2).
For monomer 1 only oligomers were produced which can be
attributed to the “negative neighboring group effect”. The
proximity of the phosphonate center to the double bond and
thus to the ruthenium carbene after catalyst attachment
probably hinders the propagation due to complexation, which
was reported previously for diallylphenyl phosphate.26 This
effect can also be seen with the naked eye as the color of the
catalyst changed from violet to brown within a few minutes,
indicating the formation of metathesis-inactive species. For all
other polycondensations, after ceasing of the ethylene
evolution, the polymers were precipitated into hexane three
times to remove the catalyst (and 1-chloronaphthalene for
solution polycondensations).
NMR spectra of the monomer (2), the polymer after ADMET
(poly(2)), and the hydrogenated PPE (poly(2)-H). It is
obvious that the terminal double bonds at 4.9 and 5.7 ppm
disappear after the ADMET process, and internal double bonds
(5.3 ppm) can be detected, which disappear after hydro-
genation (for other NMR spectra of polymer cf. Figures S13−
S18). The resulting polymers contain the expected high
amount of trans-olefins, around 80% (determined by NMR
spectroscopy), since the stereochemistry is controlled thermo-
dynamically. The polymers are readily soluble in organic
solvents such as CH2Cl2, toluene, and THF but insoluble in
hexane or methanol, for example.
Solid State Characterization. The UPPEs synthesized in
this study are all sticky viscous materials, while the hydro-
genated polymers range from sticky liquids to resin-like solids.
The thermal stability of all synthesized polymers was examined
by thermal gravimetric analysis (TGA), indicating a thermal
stability comparable with the respective poly(phosphate)s (Ton
between 260 and 300 °C). However, two degradation steps are
detected in TGA, probably due to the stable P−C bond in the
backbone (cf. Figure S22). The glass transition temperatures
(Tg) and the melting points (Tm) were determined by
differential scanning calorimetry (DSC) under nitrogen. Table
1 summarizes the thermal properties of the synthesized
Table 1. Molecular Weight andThermal Properties
(Determined by DSC) of the UPPEs and the Corresponding
PPEs
The obtained polymers exhibit irregular structures due to the
asymmetric architectures of the monomers allowing structures
as well as head-to-tail, tail-to-tail and head-to-head attachment
(see Scheme S1). The structural irregularity results in varying
distances between the phosphonate units. Compared to the
corresponding poly(phosphate)s this characteristic leads to
slightly altered properties such as a lower degree of crystallinity
and the presence of several melting endotherms (see below). In
a next step, saturated PPEs were synthesized from the obtained
polymers via catalytic hydrogenation of the double bonds using
Pd on carbon under a H2 atmosphere. After hydrogenation the
viscous UPPE changed into resin-like (for poly(4)-H) or solid
(for poly(3)-H) materials. Only poly(2)-H remained a viscous
oil after hydrogenation. The SEC results of the hydrogenated
polymers are in good agreement with the results of the UPPEs,
provingin combination with NMRthe stability of the P−C
as well as the P−O linkage under hydrogenation conditions (cf.
a
c
c
Mn
Tg
ΔHm
a
c
polymer
(g mol−1
)
Đ
(°C)
Tm (°C)
10
(J g−1
)
b
poly(2)
8700
−66
−52
n.d.
poly(3)
27900
27600
9300
1.66
1.68
2.5
−27.52
−0.9
−35.21
poly(4)
−45
14
poly(5)
−61
−61
n.d.
poly(2)-H
poly(3)-H
poly(4)-H
poly(5)-H
31000
14600
9900
1.69
1.99
2.33
−48, −40, 53
−47, −39, 10
−71.20
−17.9
−70.5
n.d.
−47
51
c
a
b
Determined by SEC. Determined by VPO. Determined by DSC.
polymers. The poly(phosphonate)s show the expected low
glass transitions ranging from −52 °C for poly(3) to −66 °C
for poly(2), which are similar to the poly(phosphate)s (Figure
3 and Figures S23−S25). Interestingly, the poly(phosphonate)s
with the longer alkyl chains, especially the hydrogenated
samples (poly(3)-H and poly(4)-H, exhibit additional thermal
transitions at low temperature at ca. −45 °C, which could be
due to the presence of different crystallite structures within the
polymer matrix due to the asymmetry of the monomers. For
poly(5)-Hthe polyphosphate analoguea glass transition of
−47 °C and a melting endotherm of ca. 51 °C are detected
(Figure S25).
1
Figures S19 and S20). Figure 2 shows an overlay of the H
The hydrogenation of the double bonds in the polymer
backbone causes a slight shift of the glass transitions but a
distinct change of the melting behavior especially of the
polymers with longer alkyl chains in the backbone. The
hydrogenation of poly(3) to poly(3)-H, for example, leads to a
shift of the main melting temperature from 10 to 53 °C and an
increase in the melting enthalpy from ca. −27 to −71 J g−1
(Figure 3). Poly(4) is amorphous, but after hydrogenation a
melting endotherm at ca. 10 °C can be detected (Figure S24).
In contrast, the short-chain poly(2) exhibits neither as
1
Figure 2. H NMR (500 MHz at 298.3 K) of monomer 2 and the
corresponding polymers poly(2) and poly(2)-H after hydrogenation.
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similar to the pseudohexagonal crystal phase of polyethylene
with a lattice spacing of 4.1 Å. The WAXS measurement
(Figure 5) yields a similar finding. In the respective angular
Figure 3. DSC thermograms of poly(3) and poly(3)-H (heating and
cooling rate 10 K min−1 (2nd run), the main melting endotherm are
labeled; for details see the main text).
unsaturated nor as hydrogenated polymer poly(2)-H crystalline
areas.
The crystalline UPPEs synthesized by ADMET polymer-
ization are considered to have a similar lamellar crystalline
structure as polyethylene, in which the phosphate units as well
as the double bonds, that can be either cis or trans, with the cis
part acting as defects and thus reducing the melting points and
enthalpies dramatically. By hydrogenation of the double bonds,
one defect can be eliminated and materials with higher degree
of crystallinity can be obtained. Recently, the crystallization
behavior of poly(phosphate)s and side-chain poly-
(phosphonate)s has been studied.27 Poly(3)-H was dissolved
in hot n-octane and crystallized slowly during cooling from
solution. Drop-cast TEM (Figure 4 and Figure S28) shows the
resulting crystals. The corresponding electron diffraction
pattern (inset, Figure 4) indicates that the crystal packing is
Figure 5. (1) Structural comparison of poly(3)-H and poly-
(phosphate). (2) X-ray diffractograms of poly(3)-H and the
corresponding poly(phosphate). (3) Temperature dependence of the
shear moduli G′ and G″ of poly(3)-H and the corresponding
polyphosphate.
range only one distinct peak at a position corresponding to a
lattice spacing of 4.1 Å appears. Furthermore, the WAXS
diffractogram reveals another noticeable feature at low angular
position, which corresponds to a structure having a periodicity
of 2.6 nm. This structural feature is found in the SAXS
measurements as well with a structural periodicity of 2.4 nm
(Figure S27). It is straightforward to assign this periodicity to
the all-trans length of the 19 methylene groups that form the
crystalline stem of one crystal lamellae. However, the thickness
of the solution grown crystals exceeds this one-fold thickness by
far, as demonstrated from the EELS thickness measurements
Figure 4. TEM bright-field micrograph and the ED pattern (inset) of
solution grown crystals of poly(3)-H from n-octane solution.
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(Figure S26). Accordingly, the poly(3)-H crystals are
assembled like a stack of folded chain lamellae.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail wurm@mpip-mainz.mpg.de, Phone 0049 6131 379
581, Fax 0049 6131 370 330 (F.R.W.).
The crystallization behavior of poly(3)-H was also compared
to a structural similar poly(phosphate) (Figure 5). The X-ray
diffractogram of the two polymers shows similar degrees of
crystallinity and a similar crystal structure as well. Even the
feature at low scattering angles in WAXS is noticeable for both
materials, which indicates the presence of polymer folded chain
crystals with a typical thickness as expected from the length of
the methylene groups between the phosphonate units.
The investigation of the mechanical properties was
accomplished by dynamic mechanical analysis (DMA) (Figure
5 (3)). To evaluate the mechanical properties of the in-chain
poly(phosphonate)s, again the poly(phosphate)s were used as
comparison. Figure 5 shows the progression of the storage (G′)
and the loss (G″) modulus with increasing temperature of
poly(3)-H and the corresponding poly(phosphate). The DMA
analysis reveals the similar viscoelastic properties of both
polymers. Below the glass transition, the storage moduli of both
polymers are relatively high due to the nearly elastic properties
at low temperatures. Above the Tg, the storage modulus
decreases significantly and the loss moduli increases due to the
softening of the material. By achieving the melting temper-
atures, the storage as well as the loss moduli decrease since the
polymers lost their rigidity. Below the melting point the
polymers differ in their behavior. The storage and the loss
moduli of the poly(phosphate) are significantly lower and
diffuse, indicating that this material is significantly softer than
the in-chain poly(phosphonate).
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors thank the Deutsche Forschungsgemeinschaft (WU
750/5-1) for support. H.T.C.T. thanks Heraeus Medical
(Wehrheim, Germany) for support.
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SUMMARY
■
This study is the first report on main-chain poly(phosphonate)s
with the P−C bond in the polymer backbone, i.e., in-chain
poly(phosphonate)s. Several structurally different monomers
with varying P content have been prepared, and their ADMET
polycondensation was studied. The resulting polymers exhibit
molecular weights up to 31 000 g/mol and show distinct
different thermal properties, depending on the length of the
alkyl spacers. The mechanical analysis of the materials reveals
similar properties to the already established poly(phosphate)s
making the in-chain poly(phosphonate)s interesting materials
for biomedical applications and as potential tissue engineering
scaffold. Many postpolymerization reactions on the internal and
external double bonds might be carried out in order to vary
their mechanical properties. Furthermore, the exchange of one
ester linkage by a stable P−C linkage inside the polymer
backbone reduces the amount of hydrophobic degradation
products. In conclusion, the in-chain poly(phosphonate)s are a
further step to complete the wide range of biomedically
interesting polyphosphonates with various architectures and
properties.
ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.macro-
mol.6b00366.
Detailed experimental procedures as well as analytical
and spectral characterization data (PDF)
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