RAFT polymerization of bio-based 1-vinyl-4-dianhydrohexitol-1,2,3-triazole stereoisomers obtained via click chemistry

Article abstract of DOI:10.1021/bm301435e

Four 1-vinyl-4-dianhydrohexitol-1,2,3-triazole stereoisomers are prepared from isomannide, isoidide, and isosorbide using an alkylation/CuAAC-ligation/ elimination three-step strategy. After characterization of the monomers by NMR, differential scanning calorimetry (DSC), and high-resolution mass spectrometry (HRMS), the corresponding stereocontrolled poly(1-vinyl-4-dianhydrohexitol-1,2, 3-triazole)s are obtained by RAFT polymerization using a xanthate chain transfer agent. A systematic investigation of the structure-properties relationship of both the monomers and polymers highlights the significant impact of the dianhydrohexitols stereochemistry on their physical properties (¹H and ¹³C NMR chemical shifts, physical state, T_g, thermal stability and solubility). A particularly original and unexpected behavior is highlighted since the two different isosorbide-based poly(1-vinyl-4- dianhydrohexitol-1,2,3-triazole) stereoisomers exhibit contrasting solubility in water.

Full text of DOI:10.1021/bm301435e

Article
pubs.acs.org/Biomac
RAFT Polymerization of Bio-Based 1‑Vinyl-4-dianhydrohexitol-1,2,3-
triazole Stereoisomers Obtained via Click Chemistry
†
†,‡
‡
†
Samir Beghdadi, Imen Abdelhedi Miladi, Hatem Ben Romdhane, Julien Bernard,
,
†,‡
and Eric Drockenmuller*
†Universite
Latarjet, 69622 Villeurbanne Cedex, France
́
Claude Bernard Lyon 1, INSA de Lyon, Ingen
́
ierie des Mater
́
iaux Polymer
̀
es (IMP - UMR CNRS 5223), 15 Boulevard
‡
̀ ́ ́
Laboratoire de Chimie Organique Structurale - Synthese et Etudes Physicochimiques, Faculte des sciences de Tunis, Universite de
Tunis El Manar, 2092 El Manar Tunis, Tunisia
‡Institut Universitaire de France (IUF), France
*
S Supporting Information
ABSTRACT: Four 1-vinyl-4-dianhydrohexitol-1,2,3-triazole stereoisomers are prepared
from isomannide, isoidide, and isosorbide using an alkylation/CuAAC-ligation/elimination
three-step strategy. After characterization of the monomers by NMR, differential scanning
calorimetry (DSC), and high-resolution mass spectrometry (HRMS), the corresponding
stereocontrolled poly(1-vinyl-4-dianhydrohexitol-1,2,3-triazole)s are obtained by RAFT
polymerization using a xanthate chain transfer agent. A systematic investigation of the
structure-properties relationship of both the monomers and polymers highlights the
significant impact of the dianhydrohexitols stereochemistry on their physical properties
1
13
(
H and C NMR chemical shifts, physical state, T , thermal stability and solubility). A
g
particularly original and unexpected behavior is highlighted since the two different
isosorbide-based poly(1-vinyl-4-dianhydrohexitol-1,2,3-triazole) stereoisomers exhibit
contrasting solubility in water.
INTRODUCTION
Among the immense library of biosourced chemicals suitable
for the generation of sustainable polymer materials,
dianhydrohexitols (DAHs), i.e., isomannide (1), isoidide (2),
to their particularly strained structure, incorporation of a small
fraction (typically 2−10 mol %) of DAH comonomer generally
affords a significant increase in the glass transition temperature
■
1
−15
1,4:3,6-
2
0,21
(
Tg).
In parallel, fully biosourced materials have also been
16
generated from the polyaddition of DAH-based monomers by
and isosorbide (3), have recently raised particular attention.
2
2−27
either AA+BB or AB+AB approaches.
Surprisingly,
DAHs are chiral, rigid, and nontoxic heterocyclic diols
composed of two cis-fused V-shaped tetrahydrofuran rings
that can be generated from cereal-based polysaccharides
whereas the preparation of DAH-based polymers by step
growth polymerization has been extensively investigated, the
synthesis of DAH-containing materials using a chain growth
polymerization process has attracted very little attention so
(
Scheme 1). These stereoisomers differ from the absolute
2
8,29
far.
Scheme 1. Isomannide (1), Isoidide (2), and Isosorbide (3)
DAHs
Although known for decades, the potential of 1-vinyl-, 4-
vinyl- and 5-vinyl-1,2,3-triazole regioisomers has been high-
3
0,31
lighted recently.
(
The spectacular development of copper-
32−36
I)-catalyzed azide−alkyne cycloaddition (CuAAC)
has
contributed to the development of a broad library of 1-vinyl-
and 4-vinyl-1,2,3-triazole regioisomers and polymer analogues
with a large variety of functional groups and physical
3
0,37−40
properties.
Thanks to the versatile character and the
functional tolerance of CuAAC, these original materials gather
the large structural diversity of vinylic polymers and the
peculiar properties of the 1,2,3-triazole ring (e.g., aromaticity,
polarity, metal complexation, adhesion properties, and H-
configuration of the C2 and C5 carbon atoms, and several
functionalized derivatives have been widely used as biobased
comonomers for step growth polymerization methods to
generate a wide range of amorphous and semicrystalline
polymers such as polyesters, polyurethanes, polyamides,
polycarbonates, polyethers, poly(ester-imide)s, poly(ester-
Received: September 13, 2012
Revised: October 18, 2012
16−19
amide)s, poly(ether-urethane)s, or polytriazoles.
Owing
©
XXXX American Chemical Society
A
dx.doi.org/10.1021/bm301435e | Biomacromolecules XXXX, XXX, XXX−XXX

Biomacromolecules
Article
1
bonding capacities). The present study intends to combine the
inherent properties of the 1,2,3-triazole and DAH groups by
developing a series of stereocontrolled biobased 1-vinyl-1,2,3-
triazole monomers and their polymer analogues using reversible
addition−fragmentation chain transfer (RAFT) polymerization.
The structure-properties relationship of these original materials
are investigated by carefully examining the impact of the DAHs
g, 9.60%) as colorless viscous oils. H NMR (400 MHz, DMSO-d
ppm): 4.72 (d, J = 7.2 Hz, OH, 1H), 4.49 (dd, J = 4.8, 4.8 Hz, H4,
H), 4.30 (dd, J = 4.8, 4.8 Hz, H3, 1H), 4.20 (oct, J = 23.2, 15.6, 2.4
6
, δ,
1
Hz, Ha, 2H), 4.17−4.06 (m, H2, H5, 2H), 3.91 (dd, J = 8.4, 6.8 Hz,
H6a, 1H), 3.79 (dd, J = 8.0, 6.8 Hz, H1a, 1H), 3.47 (dd, J = 8.4, 8.4
Hz, H6b, 1H), 3.38−3.31 (m, H1b, Hc, 2H). C NMR (100 MHz,
DMSO-d , δ, ppm): 81.65 (C4), 80.21 (Cb), 79.54 (C3), 78.88 (C2),
7.21 (Cc), 72.26 (C5), 72.00 (C6), 70.17 (C1), 57.52 (Ca). HRMS
(m/z): calcd for C H12NaO , 207.0628; found, 207.0634 [M + Na] .
Synthesis of 1,4:3,6-Dianhydro-2-O-propargyl-L-iditol (5). The
general procedure for alkylation was applied to isoidide (2, 10 g, 68
mmol), NaOH (2.8 g, 68 mmol), and propargyl bromide (7.7 mL, 68
mmol) to obtain 5 (5.75 g, 46.0%) and the corresponding dialkyne
1.84 g, 12.0%) as colorless viscous oils. H NMR (400 MHz, DMSO-
d6, δ, ppm): 5.13 (d, J = 3.6 Hz, OH, 1H), 4.53 (d, J = 4.0 Hz, H4,
H), 4.29 (d, J = 4.0 Hz, H3, 1H), 4.20 (dd, J = 2.6, 0.8 Hz, Ha, 2H),
.07−4.02 (m, H2, H5, 2H), 3.76 (d, J = 10.4 Hz, H6a, 1H), 3.70−
.64 (m, H1a, H1b, 2H), 3.62 (d, J = 9.2 Hz, H6b, 1H), 3.36 (t, J = 2.4
Hz, Hc, 1H). C NMR (100 MHz, DMSO-d , δ, ppm): 87.46 (C3),
4.34 (C4), 82.24 (C5), 80.16 (Cb), 77.18 (Cc), 74.80 (C2), 74.12
C1), 71.13 (C6), 56.18 (Ca). HRMS (m/z): calcd for C H NaO ,
07.0628; found, 207.0637 [M + Na] .
Synthesis of 1,4:3,6-Dianhydro-2-O-propargyl-D-sorbitol (6) and
,4:3,6-Dianhydro-5-propargyl-D-sorbitol (7). The general procedure
for alkylation was applied to isosorbide (3, 20.0 g, 137 mmol), NaOH
(5.50 g, 137 mmol), and propargyl bromide (20.4 mL, 137 mmol).
The crude mixture was separated by column chromatography eluting
with a 1:1 mixture of petroleum ether and ethyl acetate. After
evaporation of the solvents, 6 (2.44 g, 10.0%), 7 (6.06 g, 24.0%), 6+7,
13
6
7
+
stereochemistry on the physical properties (M , T , T , thermal
n
g
m
9 4
stability, and solubility) of both the monomers and polymers.
EXPERIMENTAL SECTION
Materials. Sodium hydroxide (NaOH, Aldrich, 98%), propargyl
bromide (Aldrich, 80 wt % in toluene), 2-chloroethanol (Aldrich,
■
1
(
9
9%), sodium azide (NaN , Alfa Aesar, 99%), copper iodide
3
1
4
3
triethylphosphite (CuIP(OEt) , Aldrich, 97%), pyridine (Aldrich,
3
anhydrous, 99.8%), mesyl chloride (Aldrich, 99%), sodium iodide
(
9
NaI, Aldrich, 99.5%), 1,8-diazabicycloundec-7-ene (DBU, Aldrich,
8%), 1,2-dimethoxyethane (glyme, Aldrich, anhydrous, 99.5%),
13
6
8
diisopropylethylamine (DIPEA, Aldrich, 99%), isosorbide (1,4:3,6-
dianhydro-D-glucitol, Aldrich, 98%), isomannide (1,4:3,6-dianhydro-D-
mannitol, Aldrich, 95%) and isoidide (1,4:3,6-dianhydro-L-iditol,
(
2
9
12
4
+
Roquette Frer
AIBN) was crystallized twice from methanol and stored at −20 °C.
O-ethyl-S-(1-phenylethyl) dithiocarbonate (17) was synthesized as
̀
es, 99%) were used as received. Azobisisobutyronitrile
1
(
41
previously described. All other reagents were purchased from Aldrich
and used as received.
Characterization Methods. NMR spectra were recorded on a
1
13
Bruker AC spectrometer at 400 MHz for H and 100 MHz for C.
High-resolution mass spectrometry (HRMS) was performed on a
MicroTOFQ-II (Bruker Daltonics, Bremen) equipped with an
electrospray ionization (ESI) ion source in positive mode. The sample
was infused at 150 μL/h in a mixture of water, methanol and
dichloromethane with 0.1% of formic acid. The gas flow of the sprayer
was 0.6 bar, the spray voltage was 3.5 kV, and the capillary temperature
was 200 °C. The mass range of the time-of-flight mass spectrometer
(
2.25 g, 8.90%), and di-O-propargyl-isosorbide (3.21 g, 11.0%) were
recovered as colorless viscous oils. Analysis of 6: H NMR (400 MHz,
DMSO-d , δ, ppm): 4.74 (s, OH, 1H), 4.43 (d, J = 4.4 Hz, H3, 1H),
1
6
4
4
1
.34 (dd, J = 4.4, 4.8 Hz, H4, 1H), 4.20 (d, J = 2.0 Hz, Ha, 2H), 4.14−
.03 (m, H2, H5, 2H), 3.86 (d, J = 10.0 Hz, H1a, 1H), 3.77 (dd, J =
0.2, 3.8 Hz, H1b, 1H), 3.71 (dd, J = 8.2, 6.6 Hz, H6a, 1H), 3.41−3.35
(
m, Hc, 1H), 3.31 (dd, J = 8.0, 8.0 Hz, H6b, 1H). 13C NMR (100
MHz, DMSO-d , δ, ppm): 84.88 (C3), 83.04 (C2), 81.50 (C4), 80.11
Cb), 77.21 (Cc), 72.27 (C1), 72.06 (C5), 71.18 (C6), 56.05 (Ca).
(
TOF) was 50−1000 m/z. For calibration, a solution of formiate was
6
(
used. X-ray diffraction experiments were performed on a suitable
crystal using a Gemini kappa-geometry diffractometer (Agilent
Technologies UK Ltd.) equipped with an Atlas CCD detector and
using Mo radiation (λ = 0.71073 Å). Size exclusion chromatography
HRMS (m/z): calcd for C H NaO , 207.0628; found, 207.0628 [M +
9
12
4
+
1
Na] . Analysis of 7: H NMR (400 MHz, DMSO-d , δ, ppm): 5.15 (s,
OH, 1H), 4.57 (dd, J = 5.8, 5.8 Hz, H4, 1H), 4.27 (d, J = 5.6 Hz, H3,
6
1
1
3
1
8
H), 4.21 (oct, J = 21.2, 17.6, 3.2 Hz, Ha, 2H), 4.16−4.08 (m, H5,
H), 4.06−4.01 (m, H2, 1H), 3.80 (dd, J = 11.6, 8.8 Hz, H6a, 1H),
.75−3.66 (m, H1, 2H), 3.46 (t, J = 3.2 Hz, Hc, 1H), 3.38 (dd, J =
(
SEC) analyses were performed on an EcoSEC semimicro GPC
system from Tosoh equipped with a dual flow refractive index (RI)
detector and a UV detector. The samples were analyzed in DMF (with
LiBr at 0.01 mol/L) at 50 °C using a flow rate of 1 mL/min. All
polymers were filtrated through a 0.45 μm pore-size membrane before
injection. Separation was performed with a guard column and two PSS
GRAM columns (7 μm, 300 × 7.5 mm). The average molar masses
0.8, 10.8 Hz, H6b, 1H). 13C NMR (100 MHz, DMSO-d , δ, ppm):
6
8.10 (C3), 80.16 (Cb), 79.41 (C4), 78.65 (C5), 77.09 (Cc), 75.33
C1), 75.28 (C2), 69.13 (C6), 56.73 (Ca). HRMS (m/z): calcd for
C H NaO , 207.0628; found, 207.0635 [M + Na] .
Synthesis of 1-Mesyl-2-azidoethanol (8). A solution of 2-
(
+
9
12
4
(
number-average molar mass M and weight-average molar mass M )
n
w
chloroethanol (20.0 g, 248 mmol) and NaN (48.3 g, 744 mmol) in
and the molar mass dispersities (Đ = M /M ) were derived from the
3
w
n
water (200 mL) was stirred at 60 °C for 48 h. After cooling the
solution at room temperature, the crude product was extracted with
diethyl ether (3 × 300 mL) to afford, after evaporation of the solvent
under reduced pressure and at room temperature, 2-azidoethanol as a
colorless liquid (19.8 g, 91.9%). Caution: Handling of this low molar
RI signal by a calibration curve based on polystyrene standards with
molar masses ranging from 580 Da to 3053 kDa. A third-degree
polynomial regression was applied. WinGPC Unity software was used
for data collection and calculation. Differential scanning calorimetry
(
2
DSC) measurements were performed under nitrogen using a DSC
4
2
mass azide is hazardous as [n +n ]/n = 1. Therefore it should be
920 (TA Instruments) at a heating rate of 20 °C/min. T values were
C
O
N
g
manipulated with extreme caution, and the crude product was thus directly
involved in the next step without further purification, handling, or storage.
measured during the second heating cycle. Thermal gravimetry
analysis (TGA) was performed under nitrogen using a TGA 2950
2
-Azidoethanol (19.8 g, 228 mmol) was dissolved in anhydrous
(
TA Instruments) at a heating rate of 10 °C/min.
pyridine (250 mL) and stirred at 0 °C under argon. Mesyl chloride
(39.2 g, 342 mmol) was then added dropwise, and the mixture was
further stirred for 24 h at room temperature under argon. The
pyridinium salt was filtered, distilled water (150 mL) was added, and
the crude product was extracted with diethyl ether (3 × 300 mL). The
General Procedure for Alkylation. Synthesis of 1,4:3,6-
Dianhydro-2-O-propargyl-D-mannitol (4). NaOH (2.8 g, 68 mmol)
was added to a solution of isomannide (1, 10 g, 68 mmol) in H O (65
2
mL) maintained at 0 °C. Propargyl bromide (7.7 mL, 68 mmol) was
added dropwise at 0 °C, and the solution was stirred for 2 additional
hours at room temperature. The crude mixture was extracted with
ethyl acetate (2 × 100 mL). The organic layer was dried with MgSO4,
filtered and concentrated under reduced pressure. The residue was
purified by column chromatography on silica gel, eluting with a 4:6
mixture of petroleum ether and ethyl acetate giving after evaporation
of the solvents 4 (4.82 g, 38.0%) and the corresponding dialkyne (1.45
organic layers were dried with MgSO , filtered, and concentrated
4
under reduced pressure. The residue was purified by column
chromatography eluting with a 6:4 mixture of petroleum ether and
ethyl acetate, giving after evaporation of the solvent 8 as a colorless oil
(14.9 g, 39.6%). As a consequence of the presence of the mesyl group
([nC + nO + n ]/nN = 2.33), 8 is much more stable than the
S
B
dx.doi.org/10.1021/bm301435e | Biomacromolecules XXXX, XXX, XXX−XXX

Biomacromolecules
Article
Scheme 2. Three-Step Synthesis of VDT Stereoisomers 13−16
corresponding alcohol. However, it is still suggested to handle this
130.30 (Cd), 121.29 (Cc), 105.27 (Ce), 87.33 (C4), 84.40 (C3),
82.48 (C2), 74.61 (C5), 73.96 (C6), 71.15 (C1), 61.67 (Ca). HRMS
compound with extreme caution and to protect it from light, high
1
+
temperature, acids, and metals. H NMR (400 MHz, CDCl , δ, ppm):
(m/z): calcd for C H N O , 254.1135; found, 254.1134 [M + H] .
3
11 16
3
4
4
.33 (t, J = 3.9 Hz, CH N , 2H), 3.6 (t, J = 3.6 Hz, OCH , 2H), 3.09
Synthesis of 15. The general procedure for the two-step synthesis
of VDTs was applied to 6 (2.02 g, 11.0 mmol), 8 (1.82 g, 11.0 mmol),
2
3
2
13
(
s, CH , 3H). C NMR (100 MHz, CDCl , δ, ppm) 67.4 (CH N ),
3
3
2
3
4
9.9 (OCH ), 37.8 (CH ).
DIPEA (1.42 g, 11.0 mmol), and CuIP(OEt) (196 mg, 0.55 mmol) to
2
3
3
General Procedure for the Two-Step Synthesis of 1-Vinyl-4-
obtain, after evaporation of the solvents, crude 11 as a slightly yellow
viscous oil. Then the general procedure for elimination was applied to
crude 11 using NaI (4.95 g, 33.0 mmol) and DBU (3.35 g, 22.0 mmol)
in anhydrous glyme (100 mL) to obtain after purification by column
chromatography on silica gel eluting with a 99:1 mixture of ethyl
dianhydrohexitol-1,2,3-triazoles (VDTs) by a CuAAC-Ligation/
Elimination Strategy. Synthesis of 13. A solution of 4 (2.02 g, 11.0
mmol) in tetrahydrofuran (THF; 10 mL) was added dropwise to a
solution of 8 (1.82 g, 11.0 mmol), DIPEA (1.42 g, 11.0 mmol) and
CuIP(OEt) (196 mg, 0.55 mmol) in THF (10 mL) maintained at 0
3
acetate and methanol 15 as a slightly yellow viscous oil (1.65 g,
1
°
C. The solution was then stirred for 24 h at 45 °C. After evaporation
5
9.1%). H NMR (400 MHz, DMSO-d , δ, ppm): 8.51 (s, Hc, 1H),
6
of the solvent and DIPEA under reduced pressure, the crude mesyl
derivative 9 was recovered as a yellow oil and involved in the
elimination reaction without further purification. Crude 9 was thus
dissolved in anhydrous glyme (100 mL) before sequential addition of
NaI (4.95 g, 33.0 mmol) and DBU (3.35 g, 22.0 mmol). The solution
was then stirred under argon for 5 h at 70 °C. The solvent was then
evaporated under reduced pressure, water (20 mL) was added, and the
residue was extracted with dichloromethane (3 × 100 mL). The
7
.50 (dd, J = 16.0, 9.0 Hz, Hd, 1H), 5.88 (dd, J = 16.0, 1.2 Hz, He-
trans, 1H), 5.22 (dd, 1H, J = 9.0, 1.2 Hz, He-cis, 1H), 4.78 (d, J = 5.8
Hz, OH, 1H), 4.62 (s, Ha, 2H), 4.45 (d, J = 4.3 Hz, H3, 1H), 4.36 (t, J
=
H6a, 3H), 3.40−3.25 (m, H6b, 1H). C NMR (100 MHz, DMSO-d ,
δ, ppm): 144.34 (Cb), 130.29 (Cd), 121.32 (Cc), 105.29 (Ce), 85.02
4.5 Hz, H4, 1H), 4.16−4.04 (m, H2, H5, 2H), 3.91−3.67 (m, H1,
13
6
(
6
C4), 83.47 (C3), 81.42 (C2), 72.35 (C6), 71.96 (C5), 71.03 (C1),
1.62 (Ca). HRMS (m/z): calcd for C H N O , 254.1135; found,
11
16
3
4
+
organic layers were dried with MgSO , filtered, and concentrated
4
254.1139 [M + H] . Single crystals of 15 suitable for X-ray diffraction
experiments were grown from a mixture of methanol and ethyl acetate.
Synthesis of 16. The general procedure for the two-step synthesis
of VDTs was applied to 7 (2.02 g, 11.0 mmol), 8 (1.82 g, 11.0 mmol),
under reduced pressure. The residue was purified by column
chromatography eluting with a 96:4 mixture of ethyl acetate and
methanol giving after evaporation of the solvents 13 as a slightly
1
yellow viscous oil (1.58 g, 56.5%). H NMR (400 MHz, DMSO-d , δ,
DIPEA (1.42 g, 11.0 mmol), and CuIP(OEt) (196 mg, 0.55 mmol) to
6
3
ppm): 8.56 (s, Hc, 1H), 7.52 (dd, J = 15.9, 9.0 Hz, Hd, 1H), 5.90 (dd,
J = 15.9, 1.5 Hz, He-trans, 1H), 5.22 (dd, J = 9.0, 1.5 Hz, He-cis, 1H),
obtain after evaporation of the solvents crude 12 as a slightly yellow
viscous oil. Then the general procedure for elimination was applied to
crude 12 using NaI (4.95 g, 33.0 mmol) and DBU (3.35 g, 22.0 mmol)
in anhydrous glyme (100 mL) to obtain after purification by column
chromatography on silica gel eluting with a 99:1 mixture of ethyl
4
.81 (d, J = 6.8 Hz, OH, 1H), 4.75−4.50 (m, Ha, H3, 3H), 4.30 (t, J =
4
.7 Hz, H4, 1H), 4.19−4.04 (m, H2, H5, 2H), 3.95−3.76 (m, H1a,
13
H6a, 2H), 3.51−3.29 (m, H1b, H6b, 2H). C NMR (100 MHz,
DMSO-d , δ, ppm): 144.36 (Cb), 130.31 (Cd), 121.32 (Cc), 105.26
acetate and methanol 16 as a slightly yellow viscous oil (1.60 g,
57.4%). H NMR (400 MHz, DMSO-d , δ, ppm): 8.51 (s, Hc, 1H),
6
1
(Ce), 81.55 (C4), 79.40 (C3), 79.23 (C2), 72.16 (C5), 71.87 (C6),
6
7
2
0.09 (C1), 62.33 (Ca). HRMS (m/z): calcd for C H N O ,
54.1135; found, 254.1137 [M + H] .
Synthesis of 14. The general procedure for the two-step synthesis
7.50 (dd, J = 15.8, 9.0 Hz, Hd, 1H), 5.90 (dd, J = 15.8, 1.2 Hz, He-
trans, 1H), 5.22 (dd, J = 9.0, 1.5 Hz, He-cis, 1H), 5.14 (d, J = 3.8 Hz,
OH, 1H), 4.79−4.57 (m, Ha, H4, 3H), 4.29 (t, J = 4.0 Hz, H3, 1H),
4.15−3.97 (m, H2, H5, 2H), 3.81−3.65 (m, H1, H6a, 3H), 3.39 (t, J =
11
16
3
4
+
of VDTs was applied to 5 (2.02 g, 11.0 mmol), 8 (1.82 g, 11.0 mmol),
8.0 Hz, H6b, 1H). 13C NMR (100 MHz, DMSO-d , δ, ppm): 144.42
DIPEA (1.42 g, 11.0 mmol), and CuIP(OEt) (196 mg, 0.55 mmol) to
3
6
obtain after evaporation of the solvents crude 10 as a slightly yellow
viscous oil. Then the general procedure for elimination was applied to
crude 10 using NaI (4.95 g, 33.0 mmol) and DBU (3.35 g, 22.0 mmol)
in anhydrous glyme (100 mL) to obtain, after purification by column
chromatography on silica gel eluting with a 99:1 mixture of ethyl
(Cb), 130.23 (Cd), 121.29 (Cc), 105.20 (Ce), 88.11 (C3), 79.39
(C4), 79.10 (C5), 75.29 (C1, C2), 69.15 (C6), 62.35 (Ca). HRMS
+
(m/z): calcd for C H N O , 254.1135; found, 254.1137 [M + H] .
11
16
3
4
General Procedure for the RAFT Polymerization of VDTs in
Dimethyl Sulfoxide (DMSO). Synthesis of 19. A solution of VDT
(14, 100 mg, 0.395 mmol), xanthate (17, 0.9 mg, 0.004 mmol), and
acetate and methanol, 14 as a slightly yellow viscous oil (1.45 g,
1
5
1.8%). H NMR (400 MHz, DMSO-d , δ, ppm): 8.55 (s, Hc, 1H),
AIBN (0.32 mg, 0.002 mmol) in DMSO-d (0.654 g) was degassed by
6
6
7
.52 (dd, J = 15.9, 9.0 Hz, Hd, 1H), 5.90 (dd, J = 15.9, 1.5 Hz, He-
three freeze−pump−thaw cycles before being sealed off under vacuum.
After 48 h at 80 °C, the polymerization medium was precipitated in
dichloromethane and dried under vacuum to recover 19 as a white
trans, 1H), 5.22 (dd, 1H, J = 9.0, 1.5 Hz, He-cis, 1H), 5.18 (d, J = 3.6
Hz, OH, 1H), 4.63 (s, Ha, 2H), 4.54 (d, J = 3.8 Hz, H3, 1H), 4.30 (d, J
=
1
3.8 Hz, H4, 1H), 4.06−3.96 (m, H2, H5, 2H), 3.81−3.60 (m, H1,
powder (60 mg, Y = 68%, M = 19.5 kDa, Đ = 1.70, T = 52 °C). H
n
g
13
H6, 4H). C NMR (100 MHz, DMSO-d , δ, ppm): 144.32 (Cb),
NMR (400 MHz, DMSO-d , δ, ppm): 7.70−7.27 (m, Hc, 1H), 5.19
6
6
C
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Table 1. Properties of VDT Stereoisomers 13−16 and Polymer Analogues 18−21 Obtained by RAFT Polymerization
a
b
b
c
c
d
monomer
m/z (Da)
Tg or Tm (°C)
polymer
Tg (°C)
M (kDa)
n
Đ
Td10 (°C)
1
1
1
1
3
4
5
6
254.1137
254.1134
254.1139
254.1137
−22
−28
139
18
19
20
21
49
52
18.2
19.5
15.0
1.65
1.70
1.56
1.60
310
318
313
312
e
118
71
−14
20.2
d
a
b
c
Obtained by HRMS. Obtained by DSC. Obtained by SEC in DMF (RI detection and PS calibration). Temperature at 10 wt % loss obtained by
e
TGA. C = 195 J/g.
p
(
2
s, OH, 1H), 4.64−4.24 (m, Ha, H2, H3, 4H), 4.10−3.86 (m, H4, H5,
H), 3.80−3.58 (m, H1, H6, 4H), 2.44−1.88 (m, Hd, He, 3H). The
same procedure was applied to the synthesis of poly(1-vinyl-4-
dianhydrohexitol-1,2,3-triazole)s (PVDTs) 18, 20, and 21.
1
Synthesis of 18. (M = 18.2 kDa, Đ = 1.65, T = 49 °C). H NMR
n
g
(
1
3
400 MHz, DMSO-d , δ, ppm): 7.70−7.27 (m, Hc, 1H), 5.19 (s, OH,
6
H), 4.64−4.24 (m, Ha, H2, H3, 4H), 4.10−3.86 (m, H4, H5, 2H),
.80−3.58 (m, H1, H6, 4H), 2.44−1.88 (m, Hd, He, 3H).
1
Synthesis of 20. (M = 15.0 kDa, Đ = 1.56, T = 118 °C). H NMR
n
g
(
1
3
400 MHz, DMSO-d , δ, ppm): 7.79−7.22 (m, Hc, 1H), 4.82 (s, OH,
6
H), 4.65−4.20 (m, Ha, H2, H3, 4H), 4.21−3.90 (m, H4, H5, 2H),
.90−3.63 (m, H1, H6, 4H), 2.54−1.78 (m, Hd, He, 3H).
Synthesis of 21. (M = 20.2 kDa, Đ = 1.60, T = 71 °C). 1H NMR
n
g
(
1
400 MHz, DMSO-d6, δ, ppm): 7.88−7.29 (m, Hc, 1H), 5.17 (s, OH,
H), 4.73−4.17 (m, Ha, H4, H5, 4H), 4.17−3.88 (m, H2, H3, 2H),
.73−3.59 (m, H1, H6, 4H), 2.56−1.72 (m, Hd, He, 3H).
3
RESULTS AND DISCUSSION
■
Synthesis of VDT Stereoisomers 13−16. VDT stereo-
isomers 13−16 were synthesized from DAHs 1−3 using a
modified procedure adapted from the pioneering work of
4
0
Hawker and co-workers (Scheme 2). Indeed, no protection of
the DAH remaining alcohol groups was required, reducing the
previously reported approach from five to three synthetic steps
and only two purifications by column chromatography. Initially,
straightforward alkylation between diols 1−3 and one
equivalent of propagyl bromide afforded mixtures of alkynes
4
−7 and the corresponding dialkyne side-products. Although
not used in the frame of this contribution, those biobased
1
Figure 1. H NMR (DMSO-d ) of alkyne-functionalized DAHs 4−7.
6
dialkynes could be advantageously valued as A monomers in,
2
24
e.g., CuAAC step growth polymerization processes. Alkynes
−7 were separated from the corresponding dialkynes by
column chromatography. As expected in the case of isosorbide
that displays two spatially nonequivalent hydroxyl groups,
4
reaction to yield the targeted VDT stereoisomers 13−16 after
purification by column chromatography (Scheme 1).
3
As a direct consequence of their distinct stereochemistry,
monomers 13, 14, and 16 were recovered as viscous oils,
whereas 15 was a crystalline solid. This was further
corroborated by DSC as stereoisomers 13, 14, and 16 exhibited
T values of −22, −28, and −14 °C, respectively, whereas a T
regioisomers 6 and 7 respectively bearing the O-propargyl
group in the C2 (exo) and C5 (endo) positions could be
isolated. Pure alkyne-functionalized DAH stereoisomers 4−7
were thus obtained as colorless viscous oils in 38, 46 and 43%
yields (for 4, 5, and 6+7, respectively). The preparation of pure
stereoisomers only differing in their spatial arrangement was
first confirmed by HRMS, as a unique molecular ion was
g
m
value of 139 °C was observed for 15 (Table 1).
Examination of single crystals of 15 by X-ray diffraction
experiments (Figure 2 and Supporting Information) confirmed
the stereochemistry of the DAH moiety as well as the presence
of a relatively strong hydrogen bonding between the hydroxyl
group on the C2 carbon atom of the DAH ring and the N3
nitrogen atom of the triazole ring from an adjacent monomer in
the crystal lattice. The geometry of this hydrogen bond (d(O−N)
= 2.88 Å and θ(OHN) = 176°) is fully consistent with the H-
1
observed whatever the nature of the initial DAH (Table 1). H
13
and C NMR spectra of alkynes 4−7 (Figure 1 and Figure S1
in the Supporting Information) undoubtedly probed the
dissimilarities of alkyne functionalized DAH in terms of
stereochemistry. Except for the alkyne group, strong disparities
in terms of chemical shift were indeed observed for all other
protons and carbons.
3
9,40,43
bonding nature of the 1,2,3-triazole ring.
The purity of
The second step relies on the CuAAC coupling between a
stoichiometric mixture of alkyne-functionalized DAHs 4−7 and
the obtained monomers was confirmed by NMR spectroscopy
and HRMS measurements. Again, HRMS spectra of VDT
stereoisomers 13−16 exhibited a single molecular ion perfectly
matching the expected theoretical value (Table 1). In analogy
with DAH-based alkynes 4−7, the chemical shifts, multiplicity
and splitting constants of the proton signals, and the chemical
1
-mesyl-2-azidoethanol 8 to afford 1-(2-mesyl-ethanol)-4-
dianhydrohexitol-1,2,3-triazole stereoisomers 9−12. After
evaporation of the volatiles, the crude mesylated 1,2,3-triazole
intermediates 9−12 were finally engaged in the elimination
D
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Biomacromolecules
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and 13C NMR spectra revealed almost identical resonances for
the vinyl and 1,2,3-triazole protons and carbons, indicating that
the electronic density of these fragments is not impacted by the
stereochemistry of the DAH moieties. Finally, the solubility of
monomers 13−16 was only slightly impacted by the stereo-
chemistry of the DAH moieties (Table 2). All stereoisomers are
Table 2. Solubility of VDT Stereoisomers 13−16 and
a
Polymer Analogues 18−21
monomers
polymers
1
3
14
15
16
18
19
20
21
H O
−
−
+
+
+
+
+
−
+
+
−
+
−
+
+
+
+
+
+
−
+
+
+
+
+
+
+
+
−
−
−
−
−
−
−
+
−
−
−
−
−
−
−
+
−
−
−
−
−
−
−
+
+
−
−
−
−
−
−
+
2
MeOH
AcOEt
Acetone
THF
+
+
+
+
+
+
+
+
CH Cl2
2
CHCl3
DMF
Figure 2. X-ray structure of VDT stereoisomer 15 (C: gray, O: red, N:
blue, H: white).
DMSO
+
+
+
+
a
shifts of carbon signals corresponding to the DAH moieties and
the methylene group adjacent to the triazole ring were
significantly impacted by the DAHs stereochemistry (Figure 3
“+” indicates solubility of about 10 mg/mL, while “−” indicates no
detectable solubility even at 0.1 mg/mL.
soluble in methanol (MeOH), acetone, dichloromethane
(
CH Cl ), dimethylformamide (DMF), and DMSO and
2 2
insoluble in water (H O). It is, however, worth mentioning
2
that, contrary to the other stereoisomers, 14 and 15 are not
soluble in chloroform (CHCl ) and ethyl acetate (AcOEt),
3
respectively.
RAFT Polymerization of VDT Stereoisomers 13−16. As
xanthates have been previously proven to be suitable chain
transfer agents (CTAs) for the controlled polymerization of
41
nonactivated N-vinyl monomers such as N-vinylcarbazole, N-
4
4
45
46
vinylindole, N-vinylphtalimide, N-vinylpyrrolidone, N-
47
40
vinylimidazolium salts, N-vinyl-1,2,3-triazoles, and N-vinyl-
,2,4-triazoles, VDT stereoisomers 13−16 were polymerized
by RAFT polymerization in DMSO-d at 80 °C using O-ethyl-
48
1
6
S-(1-phenylethyl) dithiocarbonate 17 as CTA and AIBN as
thermal initiator (Scheme 3). For each stereoisomer, the
following ratios were maintained constant, i.e., 13 wt % of
monomers 13−16 in DMSO.
For all stereoisomers, monomer conversion was monitored
1
by H NMR by following the progressive decrease of the
characteristic signals of the vinyl group at 7.5, 5.9, and 5.2 ppm
as well as the concomitant appearance of the signals of the
polymer backbone at 2.5−1.8 ppm. Another significant change
1
in the H NMR spectra was the upfield shift of the triazole
proton signal. Indeed, the well-defined singlet at about 8.5 ppm
for the monomer progressively disappears in favor of a broad
multimodal signal at about 7.8−7.3 ppm for the polymer. In
40
contrast with the contribution of Hawker and co-workers,
which underlined relatively fast kinetics for the polymerization
of 4-octyl-vinyl-1,2,3-triazole (respectively about 30 and 80% of
conversion for xanthate and dithiocarbamate mediated
polymerization during 6 h at 60 °C, [M]/[CTA]/[AIBN] =
1
Figure 3. H NMR (DMSO-d ) of VDT stereoisomers 13−16.
6
2
00:1:0.25, 10 wt % of monomer in DMF), stereoisomers 13−
and Figure S2 in the Supporting Information). In particular, the
signal of the methylene group adjacent to the triazole ring was a
singlet for 14 and 15 (OCH2 in exo position) and a
pseudoquadruplet for 13 and 16 (OCH in endo position),
again confirming the importance of spatial arrangement on the
16 displayed surprisingly slow polymerization kinetics in the
presence of 17 (i.e., about 50−70% of conversion after 48 h of
reaction at 80 °C). Similar results were obtained using a
48
49
dithiocarbamate CTA. As observed earlier, the combined
steric hindrance of the 1,2,3-triazole and DAH moieties might
hamper the polymerization kinetics of such monomers
2
1
properties of the resulting stereoisomers. Conversely, both H
E
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Biomacromolecules
Article
Scheme 3. Synthesis of Polymers 18−21 by RAFT
Polymerization of Monomers 13−16
40
compared to previously studied 1-vinyl-1,2,3-triazoles. As the
main purpose of this preliminary report is to evaluate the
properties of PVDT stereoisomers, the origin of the slow
polymerization kinetics was not investigated in the details
herein. Nevertheless, each polymerization medium remained
homogeneous throughout the polymerization process. Poly-
1
triazoles 18−21 were precipitated in CH Cl and dried under
2
2
Figure 4. H NMR (DMSO-d ) of polymers 18−21.
6
1
vacuum before characterization by SEC, H NMR, DSC, and
TGA.
As for alkynes 4−7 and 1-vinyl-1,2,3-triazole monomers 13−
values are comparable to stereocontrolled DAH-based poly-
triazoles obtained earlier by step growth polymerization (Td10 =
1
6, the stereochemistry of the DAH moieties strongly impacts
1
the H NMR chemical shifts of polymers 18−21 (Figure 4).
Whereas similar signals are observed for the vinylic backbones
and the triazole rings, strong disparities appear for the DAH
units and the adjacent methylene segments.
314−347 °C depending on the stereochemistry of the DAH
unit). The impact of the DAH stereochemistry was further
observed on the solubility of the polymers (Table 2). Although
PVDTs exhibit some common features of being soluble in
DMF and DMSO and insoluble in CH Cl , CHCl MeOH,
The polymerizations resulted in symmetrical and mono-
2
2
3,
modal SEC traces. PVDTs 18−21 display M values ranging
acetone, AcOEt, and THF, the solubility behavior of PVDTs
18−21 in water was quite unexpected. Indeed, whereas PVDTs
18−20 swell in water without dissolution of the hygroscopic
polymer chains, PVDT 21 is water-soluble. This original
behavior potentially allows the formation of amphiphilic
diblock copolymers where the two blocks are stereoisomers
of each other.
n
from 15 to 20 kDa with relatively high Đ (ranging from 1.56 to
1
.70) in regards to a controlled radical polymerization (CRP)
process (Table 1). However, these surprisingly high Đ values
may not reflect a poor control of the polymerization, as
polystyrene (PS) calibration can lead to a substantial
50
overestimation of Đ.
Similarly to the parent monomers 13−16 and corroborating
1
CONCLUSION
H NMR data, the influence of the pendent DAH stereo-
■
chemistry was clearly illustrated by DSC experiments that
underlined the amorphous character of all polymers with Tg
values of 49, 52, 118, and 71 °C for PVDTs 18−21,
respectively (Table 1). Compared to previously reported
A series of biosourced VDT stereoisomers has been synthesized
by an efficient three-step chemical pathway starting from
isomannide, isoidide, and isosorbide. The RAFT polymer-
ization of the different stereoisomers afforded a library of four
PVDTs with controlled stereochemistry and relatively well-
2
3,24
DAH-based polytriazoles,
these T values are unexpectedly
g
low considering the combination of relatively rigid, polar and
H-bonding DAH and 1,2,3-triazole groups as well as hydroxyl
functionalities. However, this probably stems from the presence
of a methylene segment between the triazole and the DAH
moieties, which provides significant mobility to the pendent
DAH moieties. Thermal stability and solubility behavior of
polymers 18−21 were then investigated. Stereochemistry of the
DAH moieties has no significant impact on the resistance to
thermal degradation since Td10 values ranging from 310 to 318
defined structures (M = 15−20 kDa and Đ ∼ 1.5−1.7). A
n
thorough investigation of the structure-properties relationship
of these novel biobased monomers and polymers highlighted a
significant influence of the DAH moieties on their phys-
icochemical properties. Interestingly, isosorbide-based PVDT
stereoisomers 20 and 21 exhibit relatively high glass transition
temperatures (T = 71 and 118 °C) and contrasting solubility
g
in water. This unique behavior together with the strong
complexation properties resulting from the combination of
triazole and dianhydrohexitol moieties, make these materials
promising candidates for the development of renewable
°
C were observed. PVDTs 18−21 are rather stable toward
degradation under nonoxidative atmosphere since these T
d10
F
dx.doi.org/10.1021/bm301435e | Biomacromolecules XXXX, XXX, XXX−XXX

Biomacromolecules
Article
chelating polymers and self-assembled nanostructures. The
study in aqueous media of random or diblock copolymers
comprising isosorbide-based stereoisomers 20 and 21 having
distinct solubility in water is currently under investigation.
(14) Firdaus, M.; Montero de Espinosa, L.; Meier, M. A. R.
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(
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5678.
ASSOCIATED CONTENT
■
*
S
3
Supporting Information
C NMR of 4-7,13-16, SEC (DMF) of 18-21, and crystallo-
graphic data of 15. This material is available free of charge via
the Internet at http://pubs.acs.org.
1
(18) Bersot, J. C.; Jacquel, N.; Saint-Loup, R.; Fuertes, P.; Rousseau,
A.; Pascault, J.-P.; Spitz, R.; Fenouillot, F.; Monteil, V. Macromol.
Chem. Phys. 2011, 212, 2114−2120.
(19) Ben Abderrazak, H.; Fildier, A.; Marque, S.; Prim, D.; Ben
AUTHOR INFORMATION
■
*
Romdhane, H.; Kricheldorf, H. R.; Chatti, S. Eur. Polym. J. 2011, 47,
2097−2110.
Corresponding Author
E-mail: eric.drockenmuller@univ-lyon1.fr.
(20) Kricheldorf, H. R.; Behnken, G.; Sell, M. J. Macromol. Sci., Part
A: Pure Appl.Chem. 2007, 44, 679−684.
21) Inkinen, S.; Stolt, M.; Sodergard, A. Biomacromolecules 2010, 11,
196−1201.
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Rapid Commun. 1998, 19, 21−26.
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24) Chatti, S.; Schwarz, G.; Kricheldorf, H. R. Macromolecules 2006,
Notes
(
1
(
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
(
Authors gratefully acknowledge the financial support from the
Centre National de la Recherche Scientifique (CNRS) among
the International Union of Pure and Applied Chemistry
(
3
9, 9064−9070.
(
IUPAC) Polymer Chemistry Funding Opportunities program,
(25) Besset, C.; Binauld, S.; Ibert, M.; Fuertes, P.; Pascault, J.-P.;
as well as from the Agence Nationale de la Recherche (ANR)
under contract ANR-10-BLAN-0932-01 [MATMAC]. The
authors are grateful to E. Jeanneau from the Centre de
Diffractometrie Henri Longchambon for the single crystal X-ray
́
data collection, structure solutions and refinements, O. Boyron
Fleury, E.; Bernard, J.; Drockenmuller, E. Macromolecules 2010, 43,
17−19.
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R. A. T. M.; Koning, C. E. J. App. Polym. Sci. 2011, 121, 1450−1463.
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41062, December 02, 2004.
29) Koyama, H.; Tsutsumi, K. (Daicel Chemical Industries). WO
Patent 113404, December 29, 2004.
30) Beghdadi, S.; Abdelhedi Miladi, I.; Addis, D.; Ben Romdhane,
for SEC experiments, Dr F. Albrieux, C. Duchamp, and N.
(
3
(
́
Henriques from the Centre Commun de Spectrometrie de
Masse (ICBMS UMR-5246) for the assistance and access to the
Mass Spectrometry facility, and Dr C. Besset for fruitful
discussions.
(
H.; Bernard, J.; Drockenmuller, E. Polym. Chem. 2012, 3, 1680−1692.
(31) Danilovtseva, E. N.; Chafeev, M. A.; Annenkov, V. V. J. Polym.
Sci., Part A: Polym. Chem. 2012, 50, 1539−1546.
DEDICATION
■
This work is dedicated to Professor Jean-Pierre Pascault on
occasion of his 68th anniversary.
(32) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B.
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