Structure-properties relationship of biosourced stereocontrolled polytriazoles from click chemistry step growth polymerization of diazide and dialkyne dianhydrohexitols

Article abstract of DOI:10.1021/bm100872h

The design of dialkyne and diazide functionalized dianhydrohexitol stereoisomers (1-6) afforded a new family of starch-based polytriazoles (7-15) with defined stereochemistry through A₂ + B₂ CuAAC step growth polymerization. The pres

Full text of DOI:10.1021/bm100872h

Biomacromolecules 2010, 11, 2797–2803
2797
Structure-Properties Relationship of Biosourced
Stereocontrolled Polytriazoles from Click Chemistry Step
Growth Polymerization of Diazide and Dialkyne
Dianhydrohexitols
Ce´line Besset, Jean-Pierre Pascault, Etienne Fleury, Eric Drockenmuller,* and
Julien Bernard*
Universite´ de Lyon, INSA-Lyon, Universite´ Claude Bernard Lyon 1, Inge´nierie des Mate´riaux Polyme`res
(UMR-CNRS 5223), F-69621 Villeurbanne Cedex, France
Received July 29, 2010; Revised Manuscript Received September 1, 2010
The design of dialkyne and diazide functionalized dianhydrohexitol stereoisomers (1-6) afforded a new
family of starch-based polytriazoles (7-15) with defined stereochemistry through A2 + B2 CuAAC step
growth polymerization. The present strategy gave rise to polytriazoles having a high biosourced weight
fraction (superior to 60% wt) and exhibiting relatively high molar masses (Mn ) 8-17 kg/mol) that could
be easily dissolved in DMF or DMSO. The obtained materials were amorphous and displayed high transition
temperatures (Tg ) 125-166 °C) as well as good resistance to thermal degradation (Td10 ) 325-347 °C).
Monomer stereochemistry proved to be a crucial parameter aiming at generating polymers with high Tg.
Thus, optimal thermal properties were obtained with monomers having RR absolute configuration of the C-2
and C-5 carbon atoms (isomannide configuration).
significant efforts have also been paid to the preparation of
derivatives with enhanced reactivity.7 For instance, amine,
isocyanate, primary alcohol, and carboxylic acid derivatives have
been reported by Thiem,8 Bortolussi,9 and Brandenburg.10
Introduction
The fossil resources depletion and rising costs are at present
driving a renewal of interest toward the development of high
performance materials derived from biomass feedstock. In this
context, increasing attention has been dedicated to the generation
of innovative and sustainable materials from the chemical
modification of inexpensive and abundant natural polymers such
as cellulose, starch, chitosan, or lignin, as well as their
derivatives.1 A second promising route to biorenewable materials
relies on the polymerization of natural or biosourced monomers.
For instance, extensive research efforts have been devoted to
the preparation of a broad array of macromolecular materials
derived from tannins,2 vegetable oils,3 furans,4 and sugars.5 One
of the most spectacular achievements in the field of biosourced
polymers is probably related to the production of starch-based
polylactide, an industrial commodity polymer with applications
in biomaterials, packaging, or fiber technology.6 Unfortunately,
the applicability of these biorenewable polyesters is currently
limited by their relatively low glass transition temperature
(Tg ) 50-60 °C) as well as their poor toughness, and it is,
therefore, of keen interest to develop a panel of new biosourced
materials exhibiting improved thermal properties and tunable
functionalities.
Consequently, a large panel of amorphous and semicrystalline
dianhydrohexitol-based materials, that is, polyamides, polyesters,
poly(ester-imide)s, poly(ether-sulfone)s, polyurethanes, poly-
(ether-urethane)s, poly(ester-amide)s, or polycarbonates, has
been generated in the last decades by copolymerizing 1,4:3,6-
dianhydrohexitol derivatives with a broad range of aliphatic or
aromatic comonomers whose chemical nature hence strongly
guided the final properties of the polymers.7,8,11 In contrast,
materials generated from the exclusive polymerization of
dianhydrohexitol-based monomers and thus displaying a high
biosourced weight fraction have been scarcely reported to
date.7,8,12 To our knowledge, only semicrystalline polythiourea
(Tg not detected, Tm ) 270 °C), polyurea (Tg not detected,
Tm ) 185-191 °C), polythiourethane (Tg not detected, Tm
)
158 °C), polyurethane (Tg ) -20-118 °C, Tm ) 120-194 °C),
and amorphous polycarbonate (Tg ) 163 °C) have been
described in the literature and the influence of monomer
stereochemistry has not been systematically discussed.
An alternative fruitful route to materials having high dian-
hydrohexitol weight fraction relies on the design of derivatives
suitable for step growth polymerization through the highly
efficient, orthogonal and regiospecific copper(I)-catalyzed
azide-alkyne cycloaddition (CuAAC).13 So far, this reaction
constitutes one of the most reliable illustrations of the “click
chemistry” philosophy,14 and several examples have notably
shown its potential to obtain functional polymer materials
through step growth polymerization.15 The CuAAC polyaddition
of natural, bioanalogous, or biosourced monomers has also been
lately explored.16 Recently, we described the synthesis of
R-azide-ω-alkyne dianhydrohexitol stereoisomers and the in-
vestigation of their polyaddition by CuAAC in solution or by
In regard to their nontoxicity, chirality, and rigidity, 1,4:3,6-
dianhydrohexitols, that is, isosorbide, isomannide, and isoidide,
constitute another promising class of biosourced monomers.7
These diols generally issued from cereal-based polysaccharides
have been thoroughly investigated in step growth polymerization
processes to generate polymers having enhanced and tunable
thermal and mechanical properties. As the secondary alcohols
of dianhydrohexitols display a relatively low reactivity that
depends on their configuration and hydrogen bonding nature,
* To whom correspondence should be addressed. E-mail: julien.bernard@
insa-lyon.fr; eric.drockenmuller@univ-lyon1.fr.
10.1021/bm100872h
 2010 American Chemical Society
Published on Web 09/16/2010

2798 Biomacromolecules, Vol. 11, No. 10, 2010
Besset et al.
13C NMR (C2D6SO): δ 80.0 (C-3, C-4), 79.7 (C-b), 78.4 (C-2, C-5),
77.3 (C-c), 70.1 (C-1, C-6), 56.8 (C-a). HRMS m/z Calcd for C12H14O6
(m/z+H), 223.0970; found, 223.0970.
solvent and copper-free thermal Huisgen polyaddition, as well
as the formation of biosourced polymer networks.17 These
approaches afforded high Tg linear polytriazoles or networks
as a consequence of the rigidity promoted by the combined
presence of 1,2,3-triazole and dianhydrohexitol heterocyclic
moieties. In the case of linear polytriazoles, monomer stereo-
chemistry and to some extent polyaddition regiospecificity
(exclusively 1,4- or mixtures of 1,4- and 1,5-disubstituted 1,2,3-
triazoles) were shown to affect the physicochemical properties
of the resulting materials. However, contrary to the thermal bulk
polyaddition process, the catalyzed polyaddition process was
somewhat limited by the physical gelation of the polymerization
media and the very poor solubility of the resulting polymers in
common organic solvents.
In the present study, we expand on our earlier work by
studying the A2 + B2 CuAAC step growth polymerization of
tailor-made diazide (A2) and dialkyne (B2) dianhydrohexitol
stereoisomers and by examining the structure/properties rela-
tionship of the resulting polytriazoles. Particularly, the impact
of monomer stereochemistry on the physicochemical properties,
that is, Mn, Tg, Td10, or solubility, of these biosourced linear
polytriazoles are discussed and compared to the polytriazoles
generated through the AB approach.
Synthesis of 1,4:3,6-Dianhydro-2,5-di-O-propargyl-D-sorbitol, 5. The
general procedure for alkylation was applied to isosorbide (510 mg,
3.5 mmol), NaH (700 mg, 17.5 mmol), and propargyl bromide (1.9
mL, 17 mmol) to obtain a yellow oil (747 mg, 96%). 1H NMR
(C2D6SO): δ 4.57 (t, J ) 4.6 Hz, H-3, 1H), 4.47 (d, J ) 4.6 Hz, H-4,
1H), 4.05-4.30 (m, H-2, H-5, C-a, 6H), 3.71-3.90 (m, H-1a, H-6a,
H-6b, 3H), 3.43-3.47 (m, H-1b, H-c, 3H); 13C NMR (C2D6SO): δ 85.1
(C-3), 82.5 (C-2), 80.0 (C-b), 79.7 (C-4), 78.4 (C-5), 77.3 (C-c), 72.3
(C-1), 69.4 (C-6), 55.9-56.8 (C-a). HRMS m/z Calcd for C12H14O6
(m/z+H), 223.0970; found, 223.0970.
Synthesis of 1,4:3,6-Dianhydro-2,5-di-O-propargyl-L-iditol, 6. The
general procedure for alkylation was applied to isoidide (510 mg, 3.5
mmol), NaH (700 mg, 17.5 mmol), and propargyl bromide (1.9 mL,
17 mmol) to obtain a yellow solid (765 mg, 98%). 1H NMR (C2D6SO):
δ 4.52 (s, H-3, H-4, 2H), 4.22 (d, J ) 2.4 Hz, H-a, 4H), 4.07-4,08
(m, H-2, H-5, 2H), 3.68-3,82 (m, H-1a, H-1b, H-6a, H-6b, 4H), 3.46
(t, J ) 2.4 Hz, H-c, 2H); 13C NMR (C2D6SO): δ 84.4 (C-3, C-4), 81.9
(C-2, C-5), 80.0 (C-b), 77.3 (C-c), 71.1 (C-1, C-6), 56.0 (C-a). HRMS
m/z Calcd for C12H14O6 (m/z+H), 223.0968; found, 223.0968.
General Procedure for the Synthesis of Polytriazoles by
Copper-Catalyzed Azide-Alkyne Cycloaddition in DMSO.
Synthesis of 7. Triethylamine (0.36 mL, 1.5 mmol) and CuIP(OEt)3 (2
mg, 0.006 mmol) were sequentially added to a stoichiometric mixture
of diazide 1 (98 mg, 0.48 mmol) and dialkyne 4 (102 mg, 0.48 mmol)
in 0.94 mL of dimethylsulfoxide. After 15 h at 60 °C, the reaction
media was precipitated into ethanol (30 mL). The solid was filtered
and dried and residual DMSO was extracted by stirring the resulting
powder for 12 h in water (4 × 15 mL) and acetone (2 × 15 mL).
Compound 7 was dried under vacuum and recovered as an orange solid
Experimental Section
Materials. Sodium hydride (Aldrich, 60% dispersion in mineral oil),
propargyl bromide (Aldrich, 80 wt % in toluene), 18-crown-6 (Aldrich,
99%), sodium azide (Alfa Aesar, 99%), dimethylformamide (DMF,
Aldrich, 99%), dimethylsulfoxide (DMSO, Aldrich, 99%), dimethyl-
sulfoxide-d6 (DMSO-d6, Aldrich, 100%), and triethylamine (Fluka,
98%) were used as received. Isosorbide, isomannide, and isoidide were
provided by Roquette Fre`res (France). Copper iodide triethylphosphite18
and 2,5-diazide-1,4:3,6- dianhydrohexitol stereoisomers 1-38a were
synthesized as previously described.
Characterization Methods. NMR spectra were recorded on a Bruker
AC spectrometer at 300 MHz for 1H and 75 MHz for 13C. High
resolution mass spectrometry (HRMS) was performed on a Ther-
moFinnigan spectrometer at the Centre de Spectrome´trie de Masse of
the Universite´ Claude Bernard Lyon 1. SEC experiments were
performed using a system consisting of a Waters apparatus (alliance
GPVC 2000 with three PL gel-mixed columns Styragel HT2-HT4-HT6)
and dual detection (refractive index and viscosimeter) operating at 120
°C and using DMSO as the mobile phase at a flow rate of 1 mL/min.
Molar masses were evaluated by means of a relative and universal
method based on PMMA standards.19 Differential scanning calorimetry
(DSC) experiments were performed under nitrogen using a DSC 2920
(TA Instruments) at a heating rate of 20 °C/min. Thermal gravimetric
analysis (TGA) measurements were performed under nitrogen using a
TGA 2950 (TA Instruments) at a heating rate of 10 °C/min.
General Procedure for the Synthesis of Dialkyne Monomers.
Synthesis of 1,4:3,6-Dianhydro-2,5-di-O-propargyl-D-mannitol, 4. NaH
(680 mg, 17 mmol) was added to a solution of isomannide (510 mg,
3.5 mmol) in 15 mL of dimethylformamide maintained at 0 °C under
argon. After hydrogen was entirely emitted, propargyl bromide (1.9
mL, 17 mmol) and 18-crown-6 (11 mg, 0.03 mmol) were added and
the mixture was then stirred 2 h at room temperature. After neutraliza-
tion of residual NaH by distilled water (5 mL), the solvents were
evaporated under reduced pressure and the residue was extracted with
dichloromethane (3 × 30 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
7:3 mixture of petroleum ether and ethyl acetate, giving after evapora-
tion of the solvents a yellow solid (745 mg, 96%). 1H NMR (C2D6SO):
δ 4.52-4.53 (m, H-3, H-4, 2H), 4.12-4.29 (m, H-2, H-5, H-a, 6H),
3.88-3.93 (m, H-1a, H-6a, 2H), 3.43-3.48 (m, H-1b, H-6b, H-c, 4H);
1
(164 mg, 83%). H NMR (C2D6SO, 300 MHz): δ 8.25 (s, H-c, 2H),
5.43-5.48 (m, H-2, H-5, 2H), 4.96-4.98 (m, H-3, H-4, 2H), 4.56-4.76
(m, H-3′, H-4′, H-a, 6H), 4.30-4.33 (m, H-2′, H-5′, 2H), 3.43-4.14
(m, H-1a, H-1b, H-6a, H-6b, H-1a′, H-1b′, H-6a′, H-6b′, 8H); 13C NMR
(C2D6SO): δ 144.0 (C-b), 124.3 (C-c), 82.4 (C-3, C-4), 79.8 (C-3′,
C-4′), 79.0 (C-2′, C-5′), 70.3 (C-1′, C-6′), 69.4 (C-1, C-6), 62.2 (C-2,
C-5), 61.8 (C-a).
Synthesis of 8. The general procedure for CuAAC polyaddition in
DMSO was applied to diazide 2 (100 mg, 0.5 mmol) and dialkyne 4
(103 mg, 0.5 mmol), triethylamine (0.36 mL, 1.5 mmol) and CuIP(OEt)3
(2 mg, 0.006 mmol) to obtain a yellow solid (189 mg, 93%). 1H NMR
(C2D6SO, 300 MHz): δ 8.25 (s, H-c, 1H), 8.17 (s, H-c, 1H), 5.37-5.40
(m, H-2, H-5, 2H), 5.01-5.05 (m, H-3, H-4, 2H), 4.53-4.71 (m, H-3′,
H-4′, H-a, 6H), 3.42-4.41 (m, H-1a, H-1b, H-6a, H-6b, H-1a′, H-1b′,
H-2′, H-5′, H-6a′, H-6b′, 10H); 13C NMR (C2D6SO): δ 144.0 (C-b),
124.4 (C-c), 123.4 (C-c), 87.3 (C-4), 81.8 (C-3), 79.8 (C-3′, C-4′), 79.0
(C-2′, C-5′), 73.1 (C-6), 70.3 (C-1′, C-6′), 68.6 (C-1), 65.5 (C-5), 62.6
(C-a), 61.9 (C-2).
Synthesis of 9. The general procedure for CuAAC polyaddition in
DMSO was applied to diazide 3 (100 mg, 0.5 mmol), dialkyne 4 (103
mg, 0.5 mmol), triethylamine (0.36 mL, 1.5 mmol), and CuIP(OEt)3
(2 mg, 0.006 mmol) to obtain a yellow solid (188 mg, 93%). 1H NMR
(C2D6SO, 300 MHz): δ 8.19 (s, H-c, 2H), 5.36-5.38 (m, H-2, H-5,
2H), 5.12-5.14 (m, H-3, H-4, 2H), 4.52-4.68 (m, H-3′, H-4′, H-a,
6H), 4.31-4.36 (m, H-2′, H-5′, 2H), 3.41-4.17 (m, H-1a, H-1b, H-6a,
H-6b, H-1a′, H-1b′, H-6a′, H-6b′, 8H); 13C NMR (C2D6SO): δ 145.2
(C-b), 123.4 (C-c), 87.0 (C-3, C-4), 79.8 (C-3′, C-4′), 79.0 (C-2′, C-5′),
72.0 (C-1, C-6), 70.2 (C-1′, C-6′), 64.9 (C-2, C-5), 62.5 (C-a).
Synthesis of 10. The general procedure for CuAAC polyaddition in
DMSO was applied to diazide 1 (100 mg, 0.5 mmol) and dialkyne 5
(103 mg, 0.5 mmol), triethylamine (0.36 mL, 1.5 mmol) and CuIP(OEt)3
1
(2 mg, 0.006 mmol) to obtain a light brown solid (142 mg, 70%). H
NMR (C2D6SO, 300 MHz): δ 8.26 (s, H-c, 2H), 5.41-5.48 (m, H-2,
H-5, 2H), 4.97-4.99 (m, H-3, H-4, 2H), 4.50-4.74 (m, H-3′, H-4′,
H-a, 6H), 3.40-4.33 (m, H-1a, H-1b, H-6a, H-6b, H-1a′, H-1b′, H-2′,

Biosourced Stereocontrolled Polytriazoles
Biomacromolecules, Vol. 11, No. 10, 2010 2799
H-5′, H-6a′, H-6b′, 10H); 13C NMR (C2D6SO): δ 144.0 (C-b), 124.4
(C-c), 85.2 (C-3′), 82.9 (C-2′), 81.9 (C-3, C-4), 79.6 (C-4′), 78.8 (C-
5′), 72.2 (C-6, C-1′), 69.4 (C-1, C-6′), 62.4 (C-a), 62.0 (C-2, C-5),
61.5 (C-a).
Scheme 1. 3D Structure of Isosorbide (SR), Isomannide (RR),
and Isoidide (SS) Dianhydrohexitol Starting Materials (from Left to
Right)
Synthesis of 11. The general procedure for CuAAC polyaddition in
DMSO was applied to diazide 2 (100 mg, 0.5 mmol), dialkyne 5 (103
mg, 0.5 mmol), triethylamine (0.36 mL, 1.5 mmol), and CuIP(OEt)3
(2.4 mg, 0.007 mmol) to obtain a brown solid (166 mg, 78%).1H NMR
(C2D6SO): δ 8.26 (s, H-c, 1H), 8.17 (s, H-c, 1H), 5.37-5.39 (m, H-2,
H-5, 2H), 5.03-5.10 (m, H-3, H-4, 2H), 4.48-4.74 (m, H-3′, H-4′,
H-a, 6H), 3.70-4.49 (m, H-1a, H-1b, H-6a, H-6b, H-1a′, H-1b′, H-2′,
H-5′, H-6a′, 9H), 3.39-3.44 (m, H-6b′, 1H); 13C NMR (C2D6SO): δ
140.4 (C-b), 137.7 (C-b), 124.5 (C-c), 123.4 (C-c), 87.2 (C-3′), 85.4
(C-2′), 83.1 (C-3), 81.8 (C-4), 79.7 (C-4′), 78.9 (C-5′), 73.1 (C-1′),
72.5 (C-6′), 69.4 (C-1), 68.6 (C-6), 65.6 (C-2), 62.5 (C-a), 61.9 (C-5),
61.6 (C-a).
Scheme 2. Synthesis of Diazide and Dialkyne Dianhydrohexitol
Monomers 1-6 Suitable for A2 + B2 CuAAC Step Growth
Polymerization
Synthesis of 12. The general procedure for CuAAC polyaddition in
DMSO was applied to diazide 3 (100 mg, 0.5 mmol), dialkyne 5 (103
mg, 0.5 mmol), triethylamine (0.36 mL, 1.5 mmol), and CuIP(OEt)3
1
(2 mg, 0.006 mmol) to obtain a light brown solid (146 mg, 72%). H
NMR (C2D6SO, 300 MHz): δ 8.19 (s, H-c, 2H), 5.36-5.37 (m, H-2,
H-5, 2H), 5.11-5.15 (m, H-3, H-4, 2H), 4.46-4.70 (m, H-3′, H-4′,
H-a, 6H), 4.32-4.37 (m, H-2′, H-5′, 2H), 3.38-4.18 (m, H-1a, H-1b,
H-6a, H-6b, H-1a′, H-1b′, H-6a′, H-6b′, 8H); 13C NMR (C2D6SO): δ
144.1 (C-b), 126.8 (C-c), 123.4 (C-c), 86.9 (C-3, C-4), 85.4 (C-4′),
83.1 (C-5′), 79.7 (C-3′), 78.9 (C-2′), 72.4 (C-6′), 72.0 (C-1, C-6), 69.3
(C-1′), 64.9 (C-2, C-5), 62.5 (C-a), 61.6 (C-a).
Synthesis of 13. The general procedure for CuAAC polyaddition in
DMSO was applied to diazide 1 (98 mg, 0.48 mmol), dialkyne 6 (102
mg, 0.48 mmol), triethylamine (0.36 mL, 1.5 mmol), and CuIP(OEt)3
(2 mg, 0.006 mmol) to obtain a yellow solid (188 mg, 93%). 1H NMR
(C2D6SO, 300 MHz): δ 8.25 (s, H-c, 2H), 5.40-5.47 (m, H-2, H-5,
2H), 4.96-4.97 (m, H-3, H-4, 2H), 4.53-4.62 (m, H-3′, H-4′, H-a,
6H), 4.26-4.32 (m, H-2′, H-5′, 2H), 3.70-4.07 (m, H-1a, H-1b, H-6a,
H-6b, H-1a′, H-1b′, H-6a′, H-6b′, 8H); 13C NMR (C2D6SO): δ 149.4
(C-b), 124.4 (C-c), 84.6 (C-3′, C-4′), 82.4 (C-3, C-4), 82.0 (C-2′, C-5′),
71.2 (C-1′, C-6′), 69.4 (C-1, C-6), 62.2 (C-2, C-5), 61.8 (C-a).
Synthesis of 14. The general procedure for CuAAC polyaddition in
DMSO was applied to diazide 2 (100 mg, 0.5 mmol), dialkyne 6 (103
mg, 0.5 mmol), triethylamine (0.36 mL, 1.5 mmol), and CuIP(OEt)3
(2 mg, 0.006 mmol) to obtain a slightly brown solid (191 mg, 94%).
1H NMR (C2D6SO, 300 MHz): δ 8.26 (s, H-c, 1H), 8.16 (s, H-c, 1H),
5.36-5.43 (m, H-2, H-5, 2H), 5.01-5.05 (m, H-3, H-4, 2H), 4.51-4.61
(m, H-3′, H-4′, H-a, 6H), 3.69-4.41 (m, H-1a, H-1b, H-6a, H-6b, H-1a′,
H-1b′, H-2′, H-5′, H-6a′, H-6b′, 10H); 13C NMR (C2D6SO): δ 143.4
(C-b), 124.8 (C-c), 124.4 (C-c), 87.2 (C-4), 84.7 (C-3′, C-4′), 82.4 (C-
3), 81.7 (C-2′, C-5′), 73.0 (C-6), 71.2 (C-1′, C-6′), 68.5 (C-1), 65.5
(C-5), 61.8 (C-2), 61.7 (C-a).
materials, which are composed of two cis-fused tetrahydrofuran
rings, nearly planar and V-shaped with a 120° angle between
rings, differ from the absolute configuration of the C-2 and C-5
carbon atoms (Scheme 1). The alcohol groups can indeed be
positioned either inside (endo position) or outside (exo position)
the polar and hydrogen bonding heterocyclic rings. When the
hydroxyl groups are in endo position (at C-5 for isosorbide and
at C-2 and C-5 for isomannide), hydrogen bonding association
with the cyclic ether groups decreases their reactivity.7b The
configuration of the different stereoisomers is also expected to
impact the rigidity and the association of the resulting poly-
triazoles and thus their physicochemical properties.
To investigate in detail the structure/properties relationship
of the dianhydrohexitol-based polytriazoles targeted herein and
evaluate the influence of monomer stereochemistry, two series
of diazide (1-3) and dialkyne (4-6) biosourced dianhydro-
hexitol stereoisomers have been prepared (Scheme 2). The
structure of these complementary monomers was also designed
to allow incorporating in the resulting polymers a high fraction
of both biosourced dianhydrohexitols and triazole rings that
possess interesting adhesion and hydrogen bonding properties.
Following a previously described procedure,8a 2,5-diazide-
1,4:3,6-dianhydrohexitols 1-3 having, respectively, RR, SR, and
SS absolute configurations of the C-2 and C-5 carbon atoms
were conveniently synthesized in two steps, respectively, from
isoidide, isosorbide, and isomannide. This synthetic pathway
involved tosylation of the alcohol groups and subsequent
nucleophilic substitution by sodium azide which proceeds
through a configuration inversion of the C-2 and C-5 carbon
atoms. Diazide monomers 1-3 were obtained as colorless oils
in moderate to relatively high yield (34, 60, and 77%,
respectively) as a result of the competition between the targeted
nucleophilic substitution and the elimination side reaction
occurring during the azidation step. The latter is particularly
significant when the tosylate is in exo position. The comple-
Synthesis of 15. The general procedure for CuAAC polyaddition in
DMSO was applied to diazide 3 (90 mg, 0.46 mmol), dialkyne 6 (100
mg, 0.46 mmol), triethylamine (0.36 mL, 1.5 mmol), and CuIP(OEt)3
1
(2 mg, 0.006 mmol) to obtain a colorless solid (182 mg, 96%). H
NMR (C2D6SO, 300 MHz): δ 8.18 (s, H-c, 2H), 5.37-5.39 (m, H-2,
H-5, 2H), 5.07-5.13 (m, H-3, H-4, 2H), 3.70-4.59 (m, H-1a, H-1b,
H-6a, H-6b, H-1a′, H-1b′, H-2′, H-3′, H-4′,H-5′, H-6a′, H-6b′, H-a,
16H); 13C NMR (C2D6SO): δ 144.0 (C-b), 124.4 (C-c), 86.9 (C-3, C-4),
84.7 (C-3′, C-4′), 82.0 (C-2′, C-5′), 72.0 (C-1, C-6), 71.2 (C-1′, C-6′),
64.8 (C-2, C-5), 61.8 (C-a).
Results and Discussion
Synthesis of Diazide and Dialkyne Dianhydrohexitol
Stereoisomers. Dianhydrohexitol stereoisomers, that is, isos-
orbide, isomannide, and isoidide, can serve as a platform to
generate a library of alkyne and azide functionalized biosourced
monomers with controlled stereochemistry suitable for A2 +
B2 CuAAC step growth polymerization. These starting diol

2800 Biomacromolecules, Vol. 11, No. 10, 2010
Besset et al.
Scheme 3. Synthesis of Polytriazoles 7-15 by CuAAC Step
Growth Polymerization of Diazides 1-3 and Dialkynes 4-6
performed at relatively high monomer concentrations of about
1 M in order to decrease the possible formation of low molar
mass cyclic species.
Figure 1. 1H NMR of diazide and dialkyne dianhydrohexitol monomers
1-6.
Conversely to the AB CuAAC polyaddition of R-azide-ω-
alkyne-dianhydrohexitols and independently of monomer
stereochemistry,17a polymerization of each dialkyne/diazide
mixture proceeded under homogeneous conditions throughout
the process. This trend may reflect the less-ordered microstruc-
ture of the polytriazoles obtained through A2 + B2 strategy (vs
AB strategy), in agreement with the significant solubility
enhancement observed in the case of polytriazoles generated
through nonregioselective AB thermal Huisgen step-growth
polymerization.17a
Polytriazoles 7-15 were precipitated twice in ethanol,
subsequently dispersed in water and then acetone to remove
DMSO traces, and recovered in high to excellent yields
(70-96%), confirming the occurrence of monomer polyaddition
(Table 1). The lower yields observed for 10, 11, or 12 are
probably due to polymer fractionation during the workup.
Whereas materials generated from AB R-azide-ω-alkyne-
dianhydrohexitols exhibited extremely poor solubility, especially
when the polyaddition was performed with a monomer having
an azide in the R configuration,17a all the polytriazoles generated
using an A2 + B2 approach could be readily dissolved in DMSO
and DMF at room temperature.
mentary 2,5-di-O-propargyl-1,4:3,6-dianhydrohexitol monomers
4-6 having, respectively, RR, SR, and SS absolute configuration
of the C-2 and C-5 carbon atoms were readily obtained in a
single step in quantitative yields (96-98%), respectively, from
isomannide, isosorbide, and isoidide, by alkylation of the
hydroxyl groups using propargyl bromide. Compounds 4 and 6
were obtained as yellow solids, whereas 5 was recovered as a
yellow oil reflecting the influence of stereochemistry on the
monomer physical state. After purification, monomers 1-6 were
1
characterized by H and 13C NMR (Figure 1 and Figure S1 in
the Supporting Information) as well as high resolution mass
spectrometry (HRMS) showing the high purity of the obtained
materials. Interestingly, the chemical shifts, multiplicity, and
splitting constants of most of the proton signals are significantly
impacted by the configuration of the diazide and dialkyne
monomers. For each series of monomers, an identical single
peak was obtained in HRMS spectra, confirming the formation
of stereoisomer derivatives. To prevent their thermal or UV
degradation, monomers 1-3 were stored at -20 °C in the dark
and under these conditions no alteration could be observed after
several months of storage.
CuAAC Step Growth Polymerization of Diazide and
Dialkyne Monomers. Screening every possible combination
of complementary monomers 1-6, dianhydrohexitol-based
polytriazoles 7-15 were generated through CuAAC polyaddi-
tion of stoichiometric mixtures of diazides 1-3 and dialkynes
4-6 in DMSO (Scheme 3). The cycloaddition reaction was
catalyzed by copper iodide triethylphosphite (CuIP(OEt)3, 0.01
equiv, according to azide or alkyne functionalities) as it is
soluble in DMSO and prevents the loss of azide chain ends
observed in the presence of the commonly used Cu(PPh3)3Br
through a Staudinger side reaction.20 Therefore, the polyaddition
process resulted exclusively in the formation of 1,4-disubstituted
1,2,3-triazole linkages, whereas the initial stoichiometry of the
dianhydrohexitol moieties remained unchanged. Triethylamine
(TEA, 1.5 equiv, according to azide or alkyne functionalities)
was used instead of diisopropylethylamine (DIPEA) as the latter
is not miscible with DMSO. In addition, polymerizations were
1H NMR analysis clearly corroborated the formation of
dianhydrohexitol/1,2,3-triazole, based polymers with the ap-
pearance of characteristic 1,4-disubstituted triazole (CHdC-N)
broad singlets and the concomitant disappearance of the alkyne
signals (CH2Ct CH), as well as the typical displacement of the
protons adjacent to the initial alkyne (CH2Ct CH) and azide
(CHN3) groups. Depending on the stereochemistry of the
monomers, either one or two triazole signals were observed at
8.15-8.19 ppm and 8.25-8.26 ppm (Figure 2). The presence
of two peaks evidenced for polytriazoles 8, 11, and 14 can be
correlated to the configuration of diazide 2 (SR), which results
in the formation of two nonequivalent CdCH-N triazole
protons. Conversely, it is worth noting that, except in the case
of polyaddition with 2, polytriazoles generated in the presence
of dialkyne 5 (SR) exhibited one single triazole peak. This
tendency probably stems from the presence of freely rotating
methylene segments surrounding the dianhydrohexitol moiety
of the dialkyne monomer.

Biosourced Stereocontrolled Polytriazoles
Biomacromolecules, Vol. 11, No. 10, 2010 2801
Table 1. Properties of Polytriazoles 7-15 Obtained by CuAAC Step Growth Polymerization of Diazides 1-3 and Dialkynes 4-6
a
diazide
(stereo.)
dialkyne
(stereo.)
Mn
a
b
No.
yield (%)
(g/mol)
DPn
PDIa
Tg (°C)
Td10 (°C)
7
1 (RR)
2 (SR)
3 (SS)
1 (RR)
2 (SR)
3 (SS)
1 (RR)
2 (SR)
3 (SS)
4 (RR)
4 (RR)
4 (RR)
5 (SR)
5 (SR)
5 (SR)
6 (SS)
6 (SS)
6 (SS)
83
93
93
70
78
72
93
94
96
9000
41
61
79
48
56
38
40
58
78
1.6
2.4
3.8
3.2
2.3
2.8
2.6
5.7
3.3
166
161
150
146
126
121
151
141
125
331
324
325
347
342
332
334
342
334
8
13300
17200
10400
12100
8200
9000
12500
16800
9
10
11
12
13
14
15
a From SEC dual detection (RI/viscosimetry) in DMSO at 120 °C. b Temperature at 10 wt % loss.
Figure 3. SEC traces (DMSO, 120 °C) of polytriazoles 7-15 obtained
by CuAAC step growth polymerization of diazides 1-3 and dialkynes
4-6.
Figure 2. 1H NMR spectra (DMSO-d6) of polytriazoles 7-15 obtained
by CuAAC step growth polymerization of diazides 1-3 and dialkynes
4-6.
SEC analysis using universal calibration (120 °C in DMSO,
dual detection RI/viscosimetry) further confirmed the generation
of polymers through CuAAC polyaddition (Figure 3). Interest-
ingly, polymerization of stoichiometric dialkyne/diazide mix-
tures afforded polytriazoles 7-15 with degrees of polymeriza-
tion (DPn) ranging from 38 to 79 and polydispersity indices
(PDI) varying from 1.6 to 5.7 (Table 1). In regard to the
polymerization process, several polytriazoles exhibited unex-
pectedly high values of PDI (for instance, PDI (9) ) 3.8 and
PDI (14) ) 5.7). The broadening of the molar mass distribution
may originate from the additional presence of high molar mass
species due to the formation of aggregates in hot DMSO (see
Figure 3) and of low molar masses cyclic species. As a
comparison, CuAAC step growth polymerization in DMSO of
R-azide-ω-alkyne-dianhydrohexitols provided polytriazoles dis-
playing lower DPn ranging from 33 to 36 and very high values
of PDI ranging from 21 to 29. Such discrepancy between the
two polyaddition systems may arise from the physical gelation
of the polymerization medium observed in the AB polyaddition
method and a stronger association of the resulting polymer
chains driven by their superior degree of stereoregularity.
Figure 4. TGA traces of polytriazoles 7-15.
Structure/Thermal Properties Relationship of Dianhydro-
hexitol-Based Polytriazoles. Thermal analyses of polytriazoles
7-15 were subsequently performed. First, their thermal resis-
tance was evaluated by TGA measurements performed under
nitrogen (Figure 4). Independently of monomer stereochemistry,
all polytriazoles exhibited a high resistance to thermal degrada-
tion with Td10 varying from 324 to 347 °C and amounts of
residual ashes of 25-30 wt %.
Furthermore, DSC experiments clearly demonstrated the
amorphous behavior of all the polymers with the exclusive
presence of a glass transition temperature (Tg) for every
polytriazole derivatives. As a result of the relatively high rigidity
of dianhydrohexitol and triazole heterocyclic moieties, high Tg
values ranging from 121 to 166 °C were observed (Table 1).

2802 Biomacromolecules, Vol. 11, No. 10, 2010
Besset et al.
2046–2064. (c) Tizzotti, M.; Charlot, A.; Fleury, E.; Stenzel, M.;
Bernard, J. Macromol. Rapid Commun. 2010 DOI: 10.1002./
marc.201000072.
These values were slightly lower than those obtained for the
CuAAC polyaddition of R-azide-ω-alkyne-dianhydrohexitols,
possibly due to the use of dialkyne and diazide monomers with
different stereochemistry and to the presence on the dialkyne
monomers of two methylene segments surrounding the dian-
hydrohexitol heterocycle, which could confer an enhanced
mobility to the polytriazole chains and thus alter their overall
rigidity. Monomers having C-2 and C-5 carbon atoms with R
absolute configuration were the best candidates aiming at
preparing polytriazoles with high Tg (Tg(7) ) 166 °C obtained
from 1 + 4), and the stereochemistry of the diazide monomer
appeared to be the key parameter to optimize the Tg of the
resulting dianhydrohexitol/triazole-based polymers. Interestingly,
this configuration corresponds to the isomannide derivative,
which is the less reactive dianhydrohexitol, as both secondary
alcohols are involved in hydrogen bonding associations. In-
versely, the introduction of dianhydrohexitol units with S
configuration at C-2 and/or C-5 in the polytriazole backbone
resulted in a drastic decrease of Tg. A close comparison of
polymers 7 and 9, 10 and 12, or 13 and 15 stressed that, for a
given configuration of the dialkyne monomer, the Tg of the
polytriazoles obtained with diazides 1 (RR), 2 (SR), and 3 (SS)
decreases in the following order: 1 > 2 > 3. A similar influence
of monomer stereochemistry was noted in the case of polytria-
zoles generated from the step growth polymerization of R-azide-
ω-alkyne dianhydrohexitol stereoisomers.17a
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Conclusions
A series of diazide and dialkyne biosourced monomers with
controlled stereochemistry (RR, SR, and SS absolute configu-
ration of the C-2 and C-5 carbon atoms) have been designed
from 1,4:3,6-dianhydrohexitols (isosorbide, isoidide and iso-
mannide). The step growth polymerization of the different
stoichiometric combinations of these complementary diazide and
dialkyne stereoisomers through copper(I)-catalyzed azide-alkyne
cycloaddition afforded a library of nine dianhydrohexitol-based
polytriazoles with defined stereochemistry allowing a fine
investigation of their structure/properties relationship. In contrast
with the previously reported AB CuAAC step growth polym-
erization strategy, the A2 + B2 synthetic approach resulted in
the generation of polytriazoles exhibiting all at once relatively
high molar masses (Mn ) 8-17 kg/mol), high glass transition
temperatures (Tg ) 121-166 °C), and good resistance to thermal
degradation (Td10 ) 325-347 °C), as well as solubility in DMSO
and DMF at room temperature. Interestingly, monomer stere-
ochemistry was shown to significantly impact the Tg of the
resulting polytriazoles and, in regard to thermal properties,
monomers having RR absolute configuration of the C-2 and C-5
carbon atoms were the best candidates aiming at preparing linear
polytriazoles with high Tg.
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Acknowledgment. Authors gratefully acknowledge the fi-
nancial support from Roquette Fre`res through the Biohub
program (http://www.biohub.fr/) as well as Patrick Fuertes and
Mathias Ibert from Roquette fre`res Research Division for fruitful
discussions.
Supporting Information Available. 13C NMR of monomers
1-6. This material is available free of charge via the Internet
at http://pubs.acs.org.
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