Isohexide hydroxy esters: Synthesis and application of a new class of biobased AB-type building blocks

Article abstract of DOI:10.1039/c4ra07896a

Here we present the synthesis of a new family of sugar derived 1,4:3,6-dianhydrohexitol based AB-type monomers, containing one methyl ester group and a secondary hydroxyl group in all four possible stereo isomers (RR, RS, SR, SS). Structural characterization of the monomers (5a-d) was established by 1D and 2D NMR analysis, which was further confirmed by single-crystal X-ray structure determination. The application of these monomers in step-growth polymerization afforded fully isohexide based stereo-regular polyesters. Homo polyesters based on the RR and RS monomers were obtained with reasonable molecular weights by melt polymerization (M_n 2400 and 2500 resp.). These materials showed unexpectedly low glass-transition temperatures of 20°C and 15°C respectively. In contrast, the monomers with SR and SS configuration yielded only low molecular weight oligomers. Surprisingly, copolymerization of the RR and SR monomers gave a polyester with higher molecular weight (M_n 4100) and a high T_g of 80°C. These preliminary results show that isohexide hydroxyesters are an intriguing new class of biobased building blocks with many potential applications.

Full text of DOI:10.1039/c4ra07896a

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DOI: 10.1039/C4RA07896A
Isohexide hydroxy esters: synthesis and application of a new class of biobased
AB-type building blocks
Shanmugam Thiyagarajan,a,b Jing Wu,a,b Rutger J. I. Knoop,a Jacco van Haveren,a,b
Martin Lutz,c and Daan S. van Es*a,b
a Food & Bioꢀbased Research, Wageningen University and Research Centre,
P.O. Box 17, 6700 AA Wageningen, The Netherlands
Fax: +31 317 483011; Tel: +31 317 481160
Eꢀmail: daan.vanes@wur.nl; shanmugam.thiyagarajan@wur.nl
b Dutch Polymer Institute, P.O. Box 902, 5600 AX, Eindhoven, The Netherlands
c Bijvoet Center for Biomolecular Research, Crystal and Structural Chemistry,
Utrecht University, Padualaan 8, 3584, Utrecht, The Netherlands
Table of contents:
Key words:
Biobased, ABꢀtype monomers, Isohexides, Polyester, 1,4:3,6ꢀdianhydrohexitol
1

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Isohexide hydroxy esters: synthesis and application of a new class of biobased
AB-type building blocks
Shanmugam Thiyagarajan,a,b Jing Wu,a,b Rutger J. I. Knoop,a Jacco van Haveren,a,b
Martin Lutz,c and Daan S. van Es*a,b
a Food & Bioꢀbased Research, Wageningen University and Research Centre,
P.O. Box 17, 6700 AA Wageningen, The Netherlands
Fax: +31 317 483011; Tel: +31 317 481160
Eꢀmail: daan.vanes@wur.nl; shanmugam.thiyagarajan@wur.nl
b Dutch Polymer Institute, P.O. Box 902, 5600 AX, Eindhoven, The Netherlands
c Bijvoet Center for Biomolecular Research, Crystal and Structural Chemistry,
Utrecht University, Padualaan 8, 3584, Utrecht, The Netherlands
Abstract
Here we present the synthesis of a new family of sugar derived 1,4:3,6ꢀ
dianhydrohexitol based ABꢀtype monomers, containing one methyl ester group and a
secondary hydroxyl group in all four possible stereo isomers (RR, RS, SR, SS).
Structural characterization of the monomers (5a-d) was established by 1D and 2D
NMR analysis, which was further confirmed by singleꢀcrystal Xꢀray structure
determination. The application of these monomers in stepꢀgrowth polymerization
afforded fully isohexide based stereoꢀregular polyesters. Homo polyesters based on
the RR and RS monomers were obtained with reasonable molecular weights by melt
polymerization (Mn 2,400 and 2,500 resp.). These materials showed unexpectedly
o
o
low glassꢀtransition temperatures of 20 C and 15 C respectively. In contrast, the
monomers with SR and SS configuration yielded only low molecular weight
oligomers. Surprisingly, copolymerization of the RR and SR monomers gave a
o
polyester with higher molecular weight (Mn 4,100) and a high Tg of 80 C. These
preliminary results show that isohexide hydroxyesters are an intriguing new class of
biobased building blocks with many potential applications.
Introduction
Reducing our dependency on finite fossil resources for the production of durable
synthetic materials is one of the main drivers for the development of chemical
building blocks from biomass. Starting from renewable, readily available biobased
feed stocks such as polysaccharides, sugars and vegetable oils, many different types
2

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of building blocks and polymeric materials based upon them have been developed
over the years.1 However, the majority of these compounds have a high intrinsic
flexibility, which often makes them unsuitable for application in e.g. engineering
plastics. Hence there remains a strong industrial interest in biobased rigid building
blocks for high Tg (glass transition temperature) polymers. Sugar derived 1,4:3,6ꢀ
dianhydrohexitols (or isohexides) are one of the few classes of bifunctional biobased
monomers that are known to increase the Tg of stepꢀgrowth polymers due to their
intrinsic rigidity.2 Isohexides are Vꢀshaped bicyclic molecules consisting of two cis
connected tetrahydrofuran rings with secondary hydroxyl groups in the 2ꢀ and 5ꢀ
positions.3 The orientation of the hydroxyl groups defines the isomeric form, which is
related to the parent hexitol (reduced C6ꢀsugar); i.e. endoꢀendo (RR, isomannide,
from Dꢀmannitol), exoꢀendo (2R5S, isosorbide, from Dꢀsorbitol), and exoꢀexo (SS,
isoidide, from Lꢀiditol) (Figure 1).
HO
O H
O H
O
O
O
O
O
O
H
O
OH
OH
(b)
(c)
(a)
Figure 1: Structure of (a) isomannide, (b) isosorbide and (c) isoidide.
Of these three isomers only isosorbide is produced on commercial scale, since
it can be relatively efficiently produced from abundantly available glucose in two
steps.3 The orientation of the secondary hydroxyl groups has a strong influence on
polymer chemistry and physics. Endoꢀhydroxyl groups (isomannide/isosorbide)
(Figure 1) are sterically shielded, making it difficult to obtain sufficient molecular
weights under mild polymerization reaction conditions. Application of more harsh
conditions often results in unwanted side reactions, such as dehydration and/or ring
opening, causing discoloration and suppressing molecular weight buildꢀup. Exoꢀ
hydroxyl groups (isoidide/isosorbide) on the other hand are sterically more
accessible, and therefore more reactive (Figure 1).2a Whereas isosorbide, due to lack
of symmetry, gives stereo irregular polymers, resulting in amorphous materials at
high levels of incorporation, the symmetrical isoidide is reported to yield semiꢀ
crystalline polymers.4 Unfortunately, since Lꢀidose (the precursor to isoidide) is not
produced in any significant levels in plants, historically the availability of isoidide as
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building block for polymers has been negligible, as are hence examples of isoidide
containing polymers. However, recently we have reported a novel efficient method for
obtaining isodide by means of catalytic epimerization of isosorbide, which could
stimulate its development as rigid building block.5
Many of the difficulties associated with using isohexides as building blocks in
stepꢀgrowth polymers (low reactivity, low molecular weights, amorphous polymers,
discoloration) are associated with the inherent low reactivity of the secondary
hydroxyl groups. Several strategies have been pursued to increase the reactivity of
isohexides by e.g. functional group substitution or chain extension. Whereas the
former approach works well in the case of isohexide diamines or diisocyanates,6 such
building blocks cannot be used for polyesters. The success of the latter approach, i.e.
chain extension, is strongly depending on the distance between the new reactive
group and the isohexide skeleton. We have recently reported on the development of
a new family of 1ꢀcarbon extended isohexide building blocks (Scheme 1).7
Furthermore we have shown that 1ꢀcarbon extension results in increased reactivity,
with retention of rigidity, and concomitant increase in Tg.4, 8
Scheme 1: Symmetrical 1ꢀcarbon extended AAꢀBB type building blocks and
polyesters derived from them (left side). Stereoꢀisomers based on AB type building
blocks and polyesters derived from them (right side).
4

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Starting from isomannide (Figure 1a), the AAꢀtype monomer isoidide
dimethylcarboxylate (IIDMC) (Scheme 1, left side) is synthesized in 3ꢀsteps which
involves modification of hydroxyl functionalities into efficient leaving groups (by Tf2O),
followed by nucleophilic substitution using cyanide and methanolysis in the last step.7
The similar idide (exoꢀexo) configuration of the ABꢀtype monomer isoidide hydroxy
ester (Scheme 1, right side) in the current work is synthesized in 4ꢀsteps starting from
isosorbide (Figure 1b). The firstꢀstep is selective monoꢀacetylation of the exo
hydroxyl group followed by triflation of the endo hydroxyl functionality in the secondꢀ
step. In the thirdꢀstep, inversion of the configuration from sorbide (endoꢀexo) to idide
(exoꢀexo) is affected by nucleophilic substitution of the triflate group by cyanide.
The nitrile and acetate are subsequently solvolyzed to afford the desired monomer.
The polyesters were synthesized by a twoꢀstep meltꢀpolycondensation procedure as
previously reported for AAꢀBBꢀtype isohexide polyesters.
Combination of isoidide diacid with rigid diols like isosorbide and isoidide
yielded fully isohexide based (AA/BBꢀtype) amorphous aliphatic polyesters with high
Tg’s (73ꢀ85°C), albeit with relatively low molecular weights (Mn 2,500). These results
prompted the question whether it would be: a) possible to use the same synthetic
methodology to prepare ABꢀtype isohexide hydroxyacids (or hydroxyesters), and b)
whether ABꢀtype polyesters based upon them would be semiꢀcrystalline (opening up
possibilities for solid state post condensation in order to increase molecular weight),
and c) what the influence would be of the stereochemistry of the reactive groups.
To the best of our knowledge there are only two reports of ABꢀtype isohexide
based monomers and corresponding polymers in the literature. In 1998, Bachmann
et al. obtained semicrystalline polyurethanes prepared either by polyaddition (or)
polycondensation of the isocyanateꢀalcohol and amineꢀcarbamic chloride monomers
respectively.9 More recently, Besset et al. synthesized αꢀazideꢀωꢀalkyne
dianhydrohexitol stereoisomers from isohexides. Copper catalyzed azideꢀalkyne
cycloaddition (CuAAC) of these monomers, in DMSO and in meltꢀpolyaddition
afforded polytriazoles.10
Here we report the synthesis of a novel class of rigid isohexide based ABꢀtype
hydroxyꢀester monomers in all four possible stereo isomers (RR, RS, SR, SS) and
preliminary results on their application in polyester synthesis. It is the objective of
this work to investigate the properties of these new building blocks and the polyesters
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derived from them. The development of industrially viable, and sustainable routes to
these monomers is outside of the scope of the present study.
Results and discussion
Monomer synthesis: Building upon the previously developed synthetic methodology
for obtaining AAꢀtype 1ꢀcarbon extended isohexides, the isohexide hydroxy
methylesters (5aꢀd) were synthesized in 4ꢀsteps starting from isosorbide (1a) or
isomannide (1b) (Scheme 2). The first step in the reaction sequence was the
selective monoꢀacetylation of isosorbide (1a) and isomannide (1b) using a
stoichiometric amount of acetic acid in the presence of
a
base 4ꢀ
dimethylaminopyridine (DMAP) and coupling agent, dicyclohexylcarbodiimide (DCC)
o
at 0 C. Good isolated yields (65ꢀ70 %) were obtained after purification by column
chromatography (silicagel, EtOAc/petr.ether). The desired products isosorbide 2ꢀ
acetate (2a) and isomannide 2ꢀacetate (2b) were obtained as white crystalline solids
in high purity (˃95 %, from NMR and GC analysis).
Subsequently, the triflate group was introduced in the second step by reacting
the isohexide monoacetates (2a & 2b) with trifluorosulfonic anhydride and pyridine in
o
dichloromethane (DCM) at ꢀ10 C. The desired products were obtained in near
quantitative yields (˃95 %). After purification by column chromatography (silicagel,
EtOAc/petr.ether), isosorbide 2ꢀacetateꢀ5ꢀtriflate (3a) and isomannide 2ꢀacetateꢀ5ꢀ
triflate (3b) were obtained as a pale yellow crystalline solid and liquid respectively in
high isolated yields (90 %) and purity (˃95 %, from NMR and GC analysis). The third
step is crucial; i.e. the nucleophilic substitution of the triflate group by cyanide using
potassium cyanide and 18ꢀcrownꢀ6 in tetrahydrofuran (THF). Strict temperature
control (ꢀ5° to 0°C) is required in order to achieve inversion of configuration at C5
affording isoidide nitrile acetate (4a) and isosorbide 5ꢀnitrileꢀ2ꢀacetate (4c),
respectively in near quantitative yield (Scheme 2). As we have previously reported,
only endoꢀoriented triflate groups will undergo efficient substitution by cyanide.7
After short path distillation of the crude products using a kugelꢀrohr oven, the
nitrileꢀacetates (4a & 4c) were obtained in up to 92 % isolated yield with high purity
(˃95 %, as determined from NMR and GC analyses). In order to obtain the remaining
two stereoisomers, during the third step the reaction temperature was gradually
increased to 40 oC for 1 h.
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Scheme 2. Synthesis of the monomers (5a-d). (i) CH3COOH, DMAP/DCC, CH2Cl2,
0oC, 3 h, 65ꢀ70 %; (ii) Tf2O, pyridine, CH2Cl2, ꢀ10~0 °C, 3 h, 91 %; (iii) KCN, 18ꢀCrꢀ6,
dry THF, ꢀ5ꢀ0 oC, 3 h, 85ꢀ92 %; (iv) KCN, 18ꢀCrꢀ6, dry THF, ꢀ5ꢀ0 oC, 3 h, 40 oC, 1 h,
65 %; (v) MeOH /HCl (c) = 1:1 mixture, reflux, 3 h, 85 %.
At this temperature, the nitrile group undergoes base induced epimerization yielding
isosorbide nitrile acetate (4b) from isoidide nitrile acetate (4a) and isomannide nitrile
acetate (4d) from isosorbide nitrile acetate (4c) in 65 % yield. Products (4b & 4d)
were obtained in high purity by short path distillation using a kugelꢀrohr oven (˃95 %,
from NMR and GC analysis). In the fourth and final step, the nitrile and acetate
groups in the product (4a-d) were solvolyzed in a methanol/conc. HCl (1:1) mixture at
reflux to afford the respective hydroxyl methylesters. Thus, the stereoꢀisomers
isoidide hydroxy methylester (5a)ꢀRR, isosorbide hydroxy methylester (5b)ꢀRS,
isosorbide hydroxy methylester (5c)ꢀSR and isomannide hydroxy methylester (5d)ꢀ
SS were obtained in high yields (85 %). Shortꢀpath distillation of the crude monomers
(kugelꢀrohr oven) afforded the products (5a-d) in high purity (˃95 %, from NMR and
GC analyses) (Figure 2). Thus, all the monomers were obtained in 4ꢀsteps in
excellent average isolated overall yields of 33 %. Full structural characterization of
the novel monomers (5aꢀd), the known precursors (2a & 2b), and the novel
intermediates (3a & 3b) and (4aꢀd) was established by FTIR, 1H NMR, 13C NMR, 2Dꢀ
NMR as well as HRMS spectroscopy (see Supporting Information). Since the
orientation of the functional groups on the isohexide rings was expected to have
considerable influence on both polymer chemistry as well as polymer properties,
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special attention was given to the structural characterisation of (5aꢀd). Due to the
rigidity, 1H NMR spectroscopy is an excellent technique for determining the
1
orientation of substituents in isohexides.11 The H NMR spectra of the pure
monomers (5a-d) are shown in Figure 2.
Despite the lack of symmetry in (5aꢀd), structural assignments are relatively
straightforward, building on previous NMR characterization of the parent isohexides.
In the exoꢀexo (RR) isomer (5a), the bridgehead protons at C3 and C4 have no clear
dihedral coupling with the respective protons at C2 and C5, resulting in a quasiꢀ
doublet multiplicity due to chemical inꢀequivalence of H3 and H4 (as can also be
observed from the 2D NMR spectra, see Supporting Information). Whereas the
proton at C2 has only a small dihedral coupling with one of the protons of the C1 ABꢀ
system, the proton at C5 appears to have comparable coupling constants with the
ABꢀsystem at C6, and therefore comparable dihedral angles. When going from (5a)
to (5b) the stereochemistry at C5 is inverted, which mainly affects the protons at C4,
C5 and C6.
8
H3COOC
4
O
5
6
1
2
3
O
OH
7
8
H3COOC
4
O
5
1
6
2
3
O
OH
7
.
Figure 2. 1H NMR spectra of the monomers (5a-d) in CDCl3
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Inversion results in a change of dihedral angles, and thus multiplicities, and to
a lesser extent in chemical shifts. The bridge proton at C4 shows a small downfield
shift, while the multiplicity changes to a quasiꢀtriplet structure due to the coupling with
the proton at C5, which also displays a radical change in multiplicity, combined with a
small downfield shift. Inversion at C2, giving (5c), results in more dramatic changes in
chemical shift compared to (5a). Complete inversion at both C2 and C5, giving (5d),
results in a spectrum that is relatively comparable to that of (5c). While the bridge
proton at C4 has shifted even more upfield, the reverse is true for the proton at C2.
Remarkable is also the increase in chemical shift difference between the protons of
the ABꢀsystem at C1.
All four hydroxyesters (5a-d) were obtained as colorless transparent oily liquids.
In order to confirm the structural characterization by NMR spectroscopy, a single
crystal Xꢀray structure determination was performed on the hydroxylꢀacid derivative
(6c)ꢀSR, obtained by the hydrolysis of hydroxyester (5c) in 3N HCl. The absolute
configuration of (6c) is shown in Figure 3.
HOOC
H
O
O
H
OH
Figure 3. Molecular structure of (6c) in the crystal. Displacement ellipsoids are drawn
at the 50% probability level.
Synthesis and Characterization of Polyesters: Fully isohexideꢀbased ABꢀtype
polyesters were synthesized by a twoꢀstep meltꢀpolycondensation procedure
(Scheme 3) as previously reported for AAꢀBBꢀtype isohexide polyesters.4, 8a During
the first stage, the reaction is carried out under nitrogen gas to form oligomers. The
o
reaction mixture is heated to 115 C, and after 15 min. the catalyst dibutyltin oxide
(DBTO, 10 mol%) is added to the flask under a continuous flow of nitrogen gas. The
o
temperature is then increased to 160 C under stirring for 12 h. At this stage the
reaction mixture became opaque and solidified. Finally the temperature was raised to
180 °C for 2 h to complete the preꢀpolymerisation reaction. In the second stage,
vacuum was applied gradually down to 0.02 mbar at 180 oC for 2 h. After completion,
the reaction mixture was cooled down to room temperature under nitrogen
atmosphere. The polymers were purified by dissolution in 5 mL of chloroform/TFA
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(6:1) followed by precipitation in 75 mL of methanol yielding white to yellow coloured
amorphous powderꢀlike materials. Typical yields were in the range of 70 ꢀ 80 %. The
1
structures of the obtained polyesters were confirmed by H, 13C, and 2ꢀD NMR
spectroscopy.
Scheme 3. Polymerization of stereoꢀisomeric monomers yielding aliphatic polyesters.
[a] (5a): C2/C5 exo; [b] (5b): C2 endo/C5 exo; [c] (5c): C2 exo/C5 endo; [d] (5d):
C2/C5 endo.
The homoꢀpolymerization of the exoꢀOH monomers (5a)ꢀRR and (5b)ꢀRS
afforded the fully isohexide based polyester PEꢀ1 and PEꢀ2 respectively in good yield
and with acceptable molecular weights (Tableꢀ1). Striking is the very low PDI of these
polymers, suggesting low conversion. These results are highly comparable to those
obtained with the AAꢀBBꢀtype polyester based on isosorbide/isoidide and isoidide
dicarboxylic acid.4
Table 1. Molecular weights, polydispersities (PDI), and isolated yields of the homoꢀ
and coꢀpolyesters prepared from different isomeric monomers.
GPCa
1H NMR
Mn
(g/mol)
2,500
2,300
Entry Monomer
Mn
(g/mol)b
2,400
Mw
Yielde Colourf Appearencei
PDId
(g/mol)c
2,500
PEꢀ1 5a (RR
PEꢀ2 5b (RS
)
1.04
1.08
83
76
p.y.g
p.y.
Op.j
Op.
)
2,500
2,700
770
(oligomers)
790
(oligomers)
PEꢀ3 5c (SR
PEꢀ4 5d (SS
)
)
1,000
980
1.29
1.24
2.55
4.10
ꢀ
ꢀ
40
35
89
78
brown
brown
d.y.h
Op.
Op.
Tp.k
Tl.l
5a:5c
PEꢀ5
4,100
2,700
10,500
11,100
n.c.m
n.c.
(RR:SR
)
5a:5d
RR:SS
PEꢀ6
brown
(
)
a. Gel Permeation Chromatography performed using HFIP as solvent; b. Mn
numberꢀaverage molecular weight; c. Mw weightꢀaverage molecular weight; d. PDI
polydispersity index; e. Isolated yield after precipitation in % relative to theoretical
maximum; f. Colour of the polyester after precipitation; g. Pale yellow; h. Deep
yellow; i. Appearence of the crude polyester in the reactor; j. Opaque; k. Transparent;
l. Translucent; m. Mn could not be calculated due to overlapping signals.
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In contrast the endoꢀOH isomers (5c)ꢀSR and (5d)ꢀSS yielded only low MW
oligomeric products (PEꢀ3 and PEꢀ4) under the typical polymerization conditions.
Again, a very low PDI was obtained. The low reactivity of these monomers is also
apparent from the low isolated yields after precipitation (Table 1). Increasing the
temperature in order to increase reactivity and molecular weight buildꢀup proved to
be detrimental, resulting in severe discoloration and gel formation, comparable to
previously reported results with the AAꢀBB system.4
Clearly the orientation of the hydroxyl group has a dramatic influence on the
reactivity of the monomers. Whereas (5a) and (5b) with exoꢀOH functionalities show
comparably moderate reactivity, monomers (5c) and (5d) with endoꢀOH groups are
much more unreactive. In contrast, the orientation of the methylester substituent does
not appear to have a significant influence on reactivity.
The reactivity of the mixture of stereoꢀisomers was also investigated by coꢀ
polymerisation of the more reactive (5a)ꢀRR isomer with the poorly reactive isomers
(5c)ꢀSR and (5d)ꢀSS. The combination of monomers (5a) and (5c) in a 1:1 ratio
surprisingly resulted in an increase in molecular weight as well as in PDI. The high
isolated yield of 89% of coꢀpolyester PEꢀ5 after precipitation proves that a significant
amount of unreactive monomer (5c) is incorporated into the polymer. In contrast,
combination of monomers (5a) and (5d) (1:1 ratio) resulted in a dramatic increase in
the PDI, indicating branching had occurred (mind however that these data are from
the precipitated polymer, so the high PDI material was still soluble in CHCl3/TFA).
Representative 1H NMR spectra of PEꢀ1 and PEꢀ2 are given in figure 4 (GPC profiles
are included in the supporting information).
1H NMR spectroscopy is a powerful tool to characterize the structure of stereo
isomers. Since the 1H NMR spectra of homopolymers PEꢀ1 and PEꢀ2 show clear and
distinctive signals, characterisation is relatively simple. For instance in the case of
PEꢀ1, the proton at C1 has a negligible dihedral coupling with the bridge proton at
C2, indicative of an idide configuration. Similarly, the proton at C4 has no significant
dihedral coupling with the bridge proton at C3, confirming retention of the idide
configuration at C4. Hence, the stereochemistry of the monomer (5a) is retained in
the polymer. The low intensity signals designated with an “e” belong to the endꢀ
group. Remarkable is the upfield shift of over 1 ppm of the proton at C4 in the endꢀ
groups compared the same proton in the repeating units in the polymer. Due to
1
severe signal overlap, the H NMR spectra of copolyesters PEꢀ5 and PEꢀ6 are too
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complicated to allow for quantification of the incorporation ratio of the two
coꢀmonomers in the copolyesters (see supporting information).
O
8
H3CO
C
4
3
O
2
5
6
1
O
O
H
7
n
PE-1
1
Figure 4. H NMR spectra of (a) monomer (5a); (b) PEꢀ1 and (c) PEꢀ2, recorded in
1
CDCl3/TFA (trifluoroacetic acidꢀd) (6:1) mixture. The numbers 1ꢀ7 in the H NMR
spectra denote the corresponding protons (as indicated in the structure) and numbers
1eꢀ7e refer to the end groups present in the polyester.
The new polyesters were also characterized by MALDIꢀToFꢀMS.
Representative mass spectra of homopolymers PEꢀ1 and PEꢀ2, as well as copolymer
PEꢀ5 are shown in figure 5. The mass spectra of PEꢀ1, PEꢀ2 and PEꢀ5 show that the
linear polymer (hydroxy and ester terminated) is the predominant species
(n*repeating unit of 156 D + MeOH). Furthermore, in the case of PEꢀ1 and PEꢀ5
macrolactones (n*repeating unit) can be observed (designated “(b)” in figure 5). In
contrast, the mass spectrum of PEꢀ2, does not show any macrolactones. This can be
rationalized by the more linear character of monomer (5b) compared to (5a), which
would more easily allow for the formation of cyclics for the latter. The mass spectrum
of PEꢀ1 also shows repeating signals for a species corresponding to the linear
polyester (a) + 28 a.u. This would correspond to the tentative structure (c), a formate
terminated linear polyester, as shown in figure 5.
12

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100
PE-1
PE-2
70
60
50
40
30
20
10
90
80
70
60
50
40
a
a
Repeating unit: 156 Da
a
Repeating unit: 156 Da
a
a
a
a
a
a
a
156 Da
156 Da
a
a
a
a
a
a
a
a
a
a
30
c
a
156 Da
c
a
a
c
20
c
b
b
c
c
a
c
c
c
c
c
b
b
b
10
1000
1500
2000
2500
3000
3500
1000
1500
2000
2500
3000
3500
Mass (m/z)
Mass (m/z)
60
50
40
30
20
10
O
C
PE-5
O
H
H
H3CO C
H
O
O
Repeating unit: 156 Da
a
a
O
O
O
H
a
O H
156 Da
a
n
n
a
(b)
(a)
a
a
a
a
b
156 Da
b
b
b
a
a
b
a
a
b
b
b
1000
1500
2000
2500
3000
3500
Mass (m/z)
Figure 5. Sections of the MALDIꢀToFꢀMS spectra of (i) homopolymer PEꢀ1 (RR); (ii)
homopolymer PEꢀ2 (RS) and (iii) copolymer PEꢀ5 (RRꢀSR), signals cationised with
K+: (a) linear polyester with methyl ester and hydroxyl endꢀgroups; (b) macrolactone;
(c) tentative structure for signal observed in PEꢀ1 spectrum.
Thermal Properties of Polyesters: Thermal properties of the new homoꢀ and coꢀ
polyesters were determined by thermogravimetric analysis (TGA) and differential
scanning calorimetry (DSC). The poor reactivity of the endoꢀhydroxyl groups in
monomers (5c) and (5d) resulted in the oligomeric products only; hence the thermal
properties of PEꢀ3 and PEꢀ4 will not be discussed here. TGA measurements were
o
o
performed from 30 C to 600 C under nitrogen atmosphere (Figure 6). The
temperature at 5 % weight loss and the maximum decomposition rates are shown in
Table 2.
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Table 2. Thermal Properties of the homoꢀ and coꢀpolyesters from TGA and DSC
analyses and their degrees of crystallinity.
DSCd
TGAa
second
heating
Dh
(%) (J/g) (J/g)
i
0
first heating
∆Hm ∆Hm
Polymer
T5%
Tmax
Tg
Tm
∆Hm
Tg
Tm
(oC)b
(oC)c
460
(oC)e
(oC)f
(J/g) (oC)e (oC)f
ꢀg
ꢀ
ꢀ
47
22
ꢀj
ꢀ
134
ꢀ
PEꢀ1
PEꢀ2
275
253
24
16
ꢀ
ꢀ
20
15
419
172
29.5
29.5
3.2
PEꢀ5
PEꢀ6
PꢀδꢀVL12
277
259
ꢀ
428
401
ꢀ
93
30
177
ꢀ
3.2
80
24
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
182
ꢀ66
58
PIsI (AAꢀBB)4
PIiI (AAꢀBB)4
PLLA
274 310/382 75 125ꢀ168 4.3
73
85
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
32 15.4
48
286 308/384
ꢀ
ꢀ
109ꢀ143 15.4
ꢀ
ꢀ
90
ꢀ
ꢀ
ꢀ
ꢀ
o
o
a. TGA was performed from 30 C to 600 C under nitrogen atmosphere; b.
temperature at 5% weight loss; c. temperature at maximum rate of decomposition; d.
o
o
DSC was performed from ꢀ60 C to 200 C with two heating and cooling runs at 10
oC/min; e. glassꢀtransition temperature; f. melting temperature; g. no melting
o
endotherm was observed up to the maximum temperature (200 C), however STA
o
analyses showed a melting endotherm at 286 C; h. degree of crystallinity from
WAXD; i. from DSC analysis; j. fully amorphous.
100
90
80
70
60
50
40
30
20
PE-5
PE-2
PE-1
PE-6
100
200
300
400
500
600
Temperature (oC)
Figure 6. TGA traces of homopolyesters PEꢀ1 and PEꢀ2, and coꢀpolyesters PEꢀ5 and
PEꢀ6 are recorded from 30 to 600 °C at 10 °C min−1 under N2 atmosphere.
14

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TGA analysis shows that despite their relatively low molecular weights the
homopolymers PEꢀ1 and PEꢀ2 are still quite thermally stable. The difference between
the TGA curves of PEꢀ1 and PEꢀ2 is striking, given the fact that both polymers are
very similar with regard to molecular weight and PDI. PEꢀ2 has a significantly lower
T5% and Tmax compared to the isomeric PEꢀ1. Compared to their AAꢀBB type
analogues reported by Wu et al. PEꢀ1 and PEꢀ2 appear to be have a higher Tmax, as
well as higher residual masses. Furthermore, while the AAꢀBB type polyesters
display distinct 2ꢀstep decomposition mechanisms, the AB analogues show a single
stage decomposition.
Comparison of the thermograms of copolyesters PEꢀ5 and PEꢀ6 shows
interesting differences. PEꢀ5 shows 2ꢀstage decomposition behavior versus single
stage for PEꢀ6. Furthermore, while the initial thermal stability of PEꢀ6 appears higher
(which could be related to the higher MW) PEꢀ5 yields almost 20% more residual
weight at 600 °C, indiciating significantly different decomposition mechanisms.
Comparison of the TGA results of the homoꢀ and copolyesters shows that
unfortunately there is no clear relationship between TGA data and isomeric
composition of the polymers.
Differential scanning calorimetry (DSC) of the polyesters gave highly surprising
results (Table 2). Previously Wu et al. reported a Tg of 85 °C for the semiꢀcrystalline
AAꢀBBꢀtype polyester of isoidide and isoidide dicarboxylic acid (PIiI, Table 2, Mn
2,500, PDI 1.4). Unexpectedly, the ABꢀtype analogue PEꢀ1 showed a Tg of only 20
°C (see also Figure 7). Furthermore, no melting endotherm was observed for PEꢀ1,
o
neither in the first nor in the second heating DSC run measured upto 200 C.
However, STA analyses (Simultaneous Thermal Analyzer ꢀ combined analyses of
o
TGA and DSC to a single sample at same time) revealed an endotherm at 286 C
(onset temperature), which is rapidly followed by the degradation of the polymer (see
supporting information). Unfortunately, increasing the polymerization temperature
above 180 oC, in order to accommodate for the high melting point, resulted in severe
discoloration of the polymers. The Visual observation of PEꢀ1 during melt
polymerization indicates semiꢀcrystallinity, since the material becomes opaque during
reaction.
In contrast, the isomeric PEꢀ2 did show melting behavior in the first run, but yet
also an unexpectedly low Tg value of 15 °C. The melting point at 172 °C is somewhat
comparable to the value of 125ꢀ168 °C reported by Wu et al. for the polyester of
15

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isosorbide and isoidide dicarboxylic acid (PIsI, Table 2). Despite a significant melting
enthalpy of approx. 30 J/g, the absence of a melting endotherm in the second
heating run (as well as (cold) crystallization) indicates a low rate of crystallization for
this polymer. Nevertheless, the Tg enhancing effect of the bicyclic isohexide skeleton
is evident by comparison with the conformationally unrestricted analogue polyꢀδꢀ
valerolactone, which results in an increase of Tg of 81ꢀ86 °C.12
Even more surprising than the low Tgs of PEꢀ1 and PEꢀ2 is the Tg value of 80 °C
recorded for coꢀpolyester PEꢀ5, which is fully in line with the results of Wu et al. Also
the observation of a melting endotherm (first run only, very low melting enthalpy) is
unexpected since a high degree of incorporation of monomer (5c) in PEꢀ5 is
expected to result in a stereoirregular, and hence amorphous polymer. The observed
low Tg for PEꢀ6 is in line with that of homopolyester PEꢀ1. In contrast to PEꢀ1,
coꢀpolyester PEꢀ6 does not have semiꢀcrystalline character, which would be
expected from the high PDI value.
0.4
0.3
0.2
0.1
PE-5
PE-1
o
Tg=80
C
0.0
o
Tg=20
C
ꢀ0.1
ꢀ0.2
ꢀ0.3
ꢀ0.4
ꢀ50
0
50
100
150
Temperature (oC)
Figure 7. Second heating DSC curves of homopolymer PEꢀ1 and copolymer PEꢀ5.
Wide-Angle X-ray Diffraction: In order to address some of the intriguing questions
that arose from the DSC analysis, preliminary WideꢀAngle Xꢀray Diffraction (WAXD)
measurements were performed on homopolyesters PEꢀ1 and PEꢀ2, as well as on coꢀ
polyester PEꢀ5 (Figure 8).
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PE-1
PE-2
PE-5
5
10
15
20
25
30
35
40
45
2 theta [o]
Figure 8. Wide angle Xꢀray powder diffraction profiles of PEꢀ1, PEꢀ2 and PEꢀ5.
The XRD diffractogram of PEꢀ1 clearly shows a high degree of crystallinity,
which is in agreement with the visual observation of high opacity of the crude material
obtained from the melt polymerization. According to DSC analysis no melting
occurred up to 200 °C, while TGAꢀDSC analysis showed a melting endotherm at
o
286 C. Hence, the highly crystalline PEꢀ1 apparently has a melting point very close
to the decomposition temperature. The diffractogram of PEꢀ2 also indicates
crystallinity, which is in agreement with the observed melting endotherm (and
significant melting enthalpy) in the DSC analysis. In contrast, WAXD analysis of
copolyester PEꢀ5 merely shows an amorphous halo, which is consistent with the
DSC data, showing only a very low melting enthalpy of 3.2 J/g.
From the WAXD diffractograms the degree of crystallinity of polyesters PEꢀ1
and PEꢀ2 were derived (Table 2). PEꢀ1 displayed a high degree of crystallinity, which
is in agreement with the observation that the material is opaque. Since according to
DSC and TGAꢀDSC analysis the melting point is close to the decomposition
temperature no heat of fusion can be calculated. In contrast, since PEꢀ2 did show
clear melting behavior and a relatively low degree of crystallinity, the estimated heat
of fusion is 134 J/g which is significantly higher than the calculated value for the AAꢀ
BB analogue reported by Wu et al. When compared to other ABꢀpolyesters it is clear
that the heat of fusion of PEꢀ2 is similar to that of its straightꢀchain analogue PꢀδꢀVL,
yet significantly higher compared to e.g. polyꢀLꢀlactic acid (PLLA).
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Combining the available data (GPC, DSC and WAXD) we propose that the
anomalously low glassꢀtransition temperatures observed for PEꢀ1 and PEꢀ2 find their
origin in the relatively low Mn and PDI (degree of polymerisation = 15ꢀ16), combined
with a high degree of crystallinity. As a result, the amorphous phase will have a high
concentration of endꢀgroups (and hence freeꢀvolume), as well as insufficient
possibilities for chain entanglement. Wu et al. reported Tg values of 85°C and 73°C
for the AAꢀBB analogues of PEꢀ1 and PEꢀ2 respectively. Although the Mn and PDI
values of those materials are comparable to those of PEꢀ1 and PEꢀ2, the observed
melting enthalpies are significantly lower, while WAXD analysis also indicated a lower
degree of crystallinity (32% for the isoidide polyester, amorphous for isosorbide).
Increasing the molecular weight of the homopolyesters PEꢀ1 and PEꢀ2 by either
adapted melt polymerization techniques or SSPC is therefore expected to have
significant effects on the Tg.
Conclusions
We have successfully synthesized and characterized a new type of 1ꢀcarbon
extended isohexide based hydroxy acids. Careful control of the reactions conditions
allowed us to obtain all four possible isomers in four steps in satisfactory yields and
high purity. The influence of the orientation of the substituents on the isohexide
skeleton on polymerization of these monomers is dramatic. Whereas the orientation
of the carboxyl group has only minor influence on reactivity, the orientation of the
hydroxyl group has a profound effect. Comparable to the parent isohexides, endoꢀ
hydroxyl groups are detrimental to reactivity and thermal stability. The molecular
weights obtained of the ABꢀtype homo polyesters of the exoꢀOH monomers (5a) and
(5b) are highly comparable to those reported for the analogous AAꢀBB type
polyester. In contrast, the thermal stabilities of the ABꢀtype homopolyesters are
higher than those of the AAꢀBB analogues. Surprisingly, the homopolymers obtained
from monomers (5a) and (5b) showed unexpectedly low Tgs, especially when
compared to their AAꢀBB analogues. Coꢀpolymerization of ABꢀmonomers (5a) and
(5c) resulted in a significant increase in MW of the ensuing polyester compared to the
homopolymer. The significantly increased Tg of the copolyester is comparable to that
of the AAꢀBB analogue. (TGA) DSC and WAXD analysis of the homopolymers PEꢀ1
and PEꢀ2 shows that these materials are highly crystalline with high melting
enthalpies, and significantly higher melting points than the AAꢀBB analogues.
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Our preliminary polymerization results show that these new rigid biobased
hydroxyesters have intriguing properties that warrant further research.
Experimental Section
Materials
Isomannide (SigmaꢀAldrich), Isosorbide (exꢀRoquette), Acetic acid (Merck, p.a.), 4ꢀ
(dimethyl amino) pyridine (DMAP, reagent plus 99% SigmaꢀAldrich), N,N'ꢀ
Dicyclohexylcarbodiimide (DCC, 99% SigmaꢀAldrich), Trifluoromethanesulfonic
anhydride (TFA, ≥99 %, Aldrich), Dichloromethane (DCM, Merck, p.a.), Pyridine
(Merck, p.a.), Hydrochloric acid (reagent grade, 37 %, SigmaꢀAldrich),
Tetrahydrofuran (THF, anhydrous, ≥99.9 %, SigmaꢀAldrich), Potassium cyanide
(extra pure, Merck), 18ꢀCrownꢀ6 (≥99 %, Fluka), Chloroform (Merck, p.a.), Methanol
(Merck, p.a.), Petroleum ether (PE, Acros Organics, 40–60 oC), Ethyl acetate (Acros
Organics, 99+ %), Silicagel (Alfa Aesar, 230ꢀ400 mesh), ChloroformꢀD (99.8 atom %
D Aldrich), Activated carbon (Norit, CN1), Magnesium sulfate (Acros Organics, 99 %
extra pure, dried, contains 3 to 4 moles of water), Celite® 545 coarse (Fluka). All
chemicals were used as received, unless denoted otherwise.
Methods
Fourier transform infrared (FTꢀIR) spectra were obtained on a Varian Scimitar 1000
FTꢀIR spectrometer equipped with a Pike MIRacle ATR Diamond/ZnSe single
reflection plate and a DTSGꢀdetector. The measurement resolution was set at 4 cmꢀ1,
and the spectra were collected in the range 4000–650 cmꢀ1 with 32 coꢀadded scans.
NMR spectra were recorded on a Bruker Avance III spectrometer operating at 400.17
MHz (1H) and 100.62 MHz (13C). Gas chromatography was performed on an
Interscience Focus GC equipped with an AS 3000 series auto sampler. Injection
volume 1 ꢁL. Injector temperature 275 °C. Split ratio 1:33. Column flow (at 275 °C)
50 mL/min helium. GC column: Restek Rxiꢀ5ms, 30 m x 0.25 mm x 0.25 ꢁm. GC
program (2,5ꢀFDA.mth); hold 2 min at 70 °C, ramp 10 °C/min, final temperature 300
°C, hold 2 min. Total run time 27 min. Detector; FID at 300 °C. GCꢀMS analysis was
performed on a Interscience TraceGC Ultra GC with AS3000 II autosampler (He
carrier gas, flow 1ml/min, split flow 20 ml/min; Restek GC column Rxiꢀ5ms 30m x
0.25mm x 0.25ꢁm; GC program hold 3 min at 50°C, ramp 7.5°C/min, final
temperature 330°C) connected to a Interscience TraceDSQ II XL quadrupole mass
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selective detector (EI, mass range 35ꢀ500 Dalton, 150 ms sample speed).
Electrospray Ionisation (ESI) mass spectrometry was carried out using a Bruker
micrOTOFꢀQ instrument in positive ion mode (capillary potential of 4500 V). Melting
points were measured on a Thermal Fisher Scientific IA 9000 Series digital melting
point apparatus. Differential Scanning Calorimetry (DSC) measurements were
conducted on a Perkin Elmer Diamond series DSC. The temperature range used was
20 °C up to 200 °C at a heating rate of 10 °C/min. Thermogravimetric analysis (TGA)
was measured with an STA 6000 (Simultaneous Thermal Analyser) from PerkinElmer
Instrument. The samples were heated from 30 to 600 °C at a heating rate of 10
°C/min under a nitrogen flow of 40 mL/min. Short path distillations were carried out
using a Buchi Glass Oven Bꢀ585 (Kugelꢀrohr). Gel Permeation Chromatography
(GPC) was performed on a Viscotek HPꢀSEC system, VEꢀ2001 GPCmax (pump and
auto sampler) equipped with TDA305 Triple Detector Array (Right Angle Light
Scattering (RALS) + Low Angle Light Scattering (LALS), Refractive Index (RI)
Detector and Viscometer). 2x GPC column PSS PFG analytical linear M and guard
column, molecular range ~250 – 2.5•10e6 D (PMMA in HFIP). Data were calculated
with OmniSECTM, Version 4.6 software. Hexafluoroisopropanol (HFIP) containing
0.02M potassium trifluoroacetate was used as eluent with a flowꢀrate of 0.7ml/min.
PMMA samples (60K and 95K, viscotek Polycal TDS) were used to calibrate the SEC
setup. Control measurements were performed with Easyvial PMMA standards from
Agilent. Wide angle Xꢀray scattering (WAXS) powder diffractograms were recorded
on a Philips PCꢀAPD diffractometer in the reflection geometry in the angular range 4ꢀ
40° (2
The Cu Ka1 radiation from the anode, generated at 40 kV and 30 mA, was
monochromatized using a 15 m Ni foil ( ) 0.1542 nm). The diffractometer was
θ), with a step size of 0.02° (2θ) and an acquisition time of 1.0 s per step.
ꢁ
λ
equipped with a 1° divergence slit, a 0.2 mm receiving slit, and a 1° scatter slit.
Matrixꢀassisted laser desorptionꢀionization timeꢀofꢀflight mass spectrometry analysis
was performed on a Bruker UltraFlextreme (Bruker Daltonics, Germany) in reflective
mode and negative ions were examined. The instrument was calibrated with a
mixture of peptide standards with known molecular masses from Bruker Daltonics.
Samples were ten times diluted in the matrix solution containing 10 mg/mL 2,5ꢀ
dihydroxybenzoic acid in 50% (v/v) acetonitrile. For analysis, 2 ꢂL of the mixture was
transferred to the target plate and dried under a stream of dry air. The lowest laser
20

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intensity needed to obtain a good quality spectrum was applied and 9 times 50 laser
shots, randomly obtained from the sample, were accumulated.
X-ray crystal structure determination of (6c)
C7H10O5, Fw = 174.15, colourless block, 0.30 x 0.28 x 0.12 mm3, triclinic, P1 (no. 1),
a = 5.0392(2), b = 5.4022(2), c = 7.5864(3) Å, α = 99.295(3), β = 102.547(2), γ =
102.956(3) º, V = 191.598(15) Å3, Z = 1, Dx = 1.509 g/cm3, ꢀ = 0.13 mmꢀ1. 5668
Reflections were measured on a Bruker Kappa ApexII diffractometer with sealed tube
and Triumph monochromator (λ = 0.71073 Å) at a temperature of 100(2) K up to a
resolution of (sin θ/λ)max = 0.65 Åꢀ1. Intensity data were integrated with the Eval15
software.13 Absorption correction and scaling was performed with SADABS
(correction range 0.70ꢀ0.75).14 1706 Reflections were unique (Rint = 0.014), of which
1691 were observed [I>2σ(I)]. The structure was solved with the program SHELXSꢀ
97.15 Leastꢀsquares refinement was performed with SHELXLꢀ201315 against F2 of all
reflections. Nonꢀhydrogen atoms were refined freely with anisotropic displacement
parameters. All hydrogen atoms were located in difference Fourier maps. OꢀH
hydrogen atoms were refined freely with isotropic displacement parameters, CꢀH
hydrogen atoms were refined with a riding model. 117 Parameters were refined with
3 restraints (floating origin). R1/wR2 [I > 2σ(I)]: 0.0247 / 0.0642. R1/wR2 [all refl.]:
0.0250 / 0.0646. S = 1.070. The absolute structure could not be determined reliably
from anomalous differences. Residual electron density between 0.15 and 0.30 e/Å3.
Geometry calculations and checking for higher symmetry was performed with the
PLATON program.16 CCDC “964358” contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
(3S,6R)-6-hydroxyhexahydrofuro[3,2-b]furan-3-yl acetate (2a)
A 500 mL twoꢀnecked roundꢀbottom flask, equipped with a magnetic stirrer, and a
reflux condenser with a nitrogen inlet, was charged with isosorbide (1a, 25.0 g, 0.171
mol), acetic acid (10.7 mL, 0.188 mol) and DCM (300 mL). The reaction mixture was
stirred at room temperature under nitrogen atmosphere for 10 min. The solution was
o
then cooled down to 0 C and DCC (38.8 g, 0.188 mol) followed by DMAP (0.20 g,
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1.710 mmol) was added portionꢀwise. A white crystalline precipitate of N,Nˈꢀ
dicyclohexylurea was formed immediately. The reaction progress was monitored by
TLC analysis (ethylacetate/PE, 2:3). After 3 h, when the reaction was completed, the
mixture was filtered off to remove N,Nˈꢀdicyclohexylurea and washed with DCM (2 X
100 mL). The combined filtrates were washed with water (2 X 500 mL), dried over
magnesium sulfate and evaporated under reduced pressure to give the crude mixture
of isosorbide 2ꢀacetate, isosorbide 5ꢀacetate and isosorbide 2,5ꢀdiacetate. The
desired product, isosorbide 2ꢀacetate (2a) was separated by column chromatography
on silica gel (ethylacetate/PE, 1:4) to obtain (2a) as a white crystalline solid.
Yield: 20.6 g, 64 %; m.p. 79–81 oC (lit.17 m.p. 78 oC); 1H NMR (400 MHz, CDCl3): δ =
5.27 – 5.17 (m, 1H), 4.63 (t,
7.1, 5.6 Hz, 1H), 4.02 (t, = 2.5 Hz, 2H), 3.89 (dd,
9.5, 6.0 Hz, 1H), 2.65 (d,
J
= 4.9 Hz, 1H), 4.48 (d,
J
= 4.3 Hz, 1H), 4.31 (dd,
J
=
=
J
J
= 9.5, 6.0 Hz, 1H), 3.57 (dd,
J
J
= 7.3 Hz, 1H), 2.09 (s, 3H) ppm; 13C NMR (100 MHz,
CDCl3): δ = 167.77, 83.45, 79.79, 76.23, 71.43, 71.35, 70.12, 18.71 ppm; IR (neat): ʋ
= 3404, 2925, 2884, 1733, 1372, 1254, 1047, 1010, 989 cm–1; HRMS (ESI): MH+,
found 189.0757. C8H13O5 requires 189.0763.
(3R,6R)-6-hydroxyhexahydrofuro[3,2-b]furan-3-yl acetate (2b)
A 500 mL twoꢀnecked roundꢀbottom flask, equipped with a magnetic stirrer, and a
reflux condenser with a nitrogen inlet, was charged with isomannide (1b, 25.0 g,
0.171 mol), acetic acid (10.7 mL, 0.188 mol) and DCM (300 mL). The reaction
mixture was stirred at room temperature under nitrogen atmosphere for 10 min. The
o
solution was then cooled down to 0 C and DCC (38.8 g, 0.188 mol) followed by
DMAP (0.20 g, 1.710 mmol) was added portionꢀwise. A white crystalline precipitate of
N,Nˈꢀdicyclohexylurea was formed immediately. The reaction progress was followed
by TLC analysis (ethylacetate/PE, 3:2). After 3 h, when the reaction was completed,
the mixture was filtered off to remove N,Nˈꢀdicyclohexylurea and washed with DCM
(2 X 100 mL). The combined filtrates were washed with water (2 X 500 mL), dried
over magnesium sulfate and evaporated under reduced pressure to give the crude
mixture of isomannide 2ꢀacetate and isomannide 2,5ꢀdiacetate. The desired product,
isomannide 2ꢀacetate (2b) was separated by column chromatography on silica gel
(ethylacetate/PE, 2:3). to obtain (2b) as a white crystalline semiꢀsolid.
1
Yield: 22.5 g, 70 %; H NMR (400 MHz, CDCl3): δ = 5.14 (td,
J = 6.5, 5.4 Hz, 1H),
4.69 (t,
J
= 5.1 Hz, 1H), 4.48 (t,
J
= 5.2 Hz, 1H), 4.36 – 4.24 (m, 1H), 4.11 (dd,
J
=
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9.4, 6.5 Hz, 1H), 3.97 (dd,
(dd,
J
= 9.1, 6.3 Hz, 1H), 3.84 (dd, J = 9.4, 6.6 Hz, 1H), 3.58
J
= 9.1, 7.1 Hz, 1H), 2.81 (d, J
= 8.2 Hz, 1H), 2.13 (s, 3H) ppm; 13C NMR (100
MHz, CDCl3): δ = 170.11, 81.35, 80.19, 73.89, 73.55, 72.05, 70.39, 20.36 ppm; IR
(neat): ʋ = 3518, 2956, 2878, 1726, 1386, 1228, 1099, 1059, 1021, 931 cm–1; HRMS
(ESI): MH+, found 189.0757. C8H13O5 requires 189.0763.
(3S,6R)-6-(((trifluoromethyl)sulfonyl)oxy)hexahydrofuro[3,2-b]furan-3-yl acetate
(3a)
A 500 mL 3ꢀnecked roundꢀbottom flask, equipped with a magnetic stirrer and a
dropping funnel, was charged with (2a) (15.0 g, 0.079 mol), pyridine (10 mL, 0.119
mol) and DCM (350 mL). The colorless solution was cooled down to ꢀ10 °C under
nitrogen atmosphere. Trifluoromethanesulfonic anhydride (20 mL, 0.119 mol) was
added dropꢀwise over 1 h. The progress of the reaction was followed by GCꢀMS
analysis, which indicated that the reaction had gone to completion after 3 h. The
reaction mixture was then poured onto iceꢀwater (500 mL) and stirred for 15 min. The
organic layer was separated, and the water layer was extracted with DCM (2 x 150
mL). The combined organic layers were subsequently washed with aqueous HCl (1.0
M, 3 x 300 mL), water (2 x 300 mL), dried over MgSO4, and decolorized with
activated carbon. After filtration through a Gꢀ3 glass filter funnel containing Celite, the
resulting clear solution was evaporated under reduced pressure using a rotary
evaporator. Thus obtained crude product was further purified by column
chromatography on silica gel (ethylacetate/PE, 1:4)., to obtain (3a) as a pale yellow
colored crystalline solid.
Yield: 23.0 g, 90.1 %; m.p. 32–34 oC; 1H NMR (400 MHz, CDCl3): δ = 5.23 (t,
Hz, 2H), 4.90 (t, = 5.3 Hz, 1H), 4.49 (d, = 5.0 Hz, 1H), 4.16 – 4.01 (m, 3H), 3.90
(dd,
= 11.3, 4.8 Hz, 1H), 2.09 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ = 169.64,
J = 4.1
J
J
J
123.00, 119.83, 116.65, 113.48, 86.05, 85.29, 80.57, 73.47, 70.49, 20.53 ppm; IR
(neat): ʋ = 3517, 2949, 2877, 1727, 1410, 1234, 1198, 1143, 1097, 966 cm–1; HRMS
(ESI): MH+, found 321.0237. C9H12F3O7S requires 321.0256.
(3R,6R)-6-(((trifluoromethyl)sulfonyl)oxy)hexahydrofuro[3,2-b]furan-3-yl acetate
(3b)
A 500 mL 3ꢀnecked roundꢀbottom flask, equipped with a magnetic stirrer and a
dropping funnel, was charged with (2b) (15.0 g, 0.079 mol), pyridine (10 mL, 0.119
23

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mol) and DCM (350 mL). The colorless solution was cooled down to ꢀ10 °C under
nitrogen atmosphere. Trifluoromethanesulfonic anhydride (20 mL, 0.119 mol) was
added dropꢀwise over 1 h. The progress of the reaction was followed by GCꢀMS
analysis, which indicated that the reaction had gone to completion after 3 h. The
reaction mixture was then poured onto iceꢀwater (500 mL) and stirred for 15 min. The
organic layer was separated, and the water layer was extracted with dichloromethane
(2 x 150 mL). The combined organic layers were subsequently washed with aqueous
HCl (1.0 M, 3 x 300 mL), water (2 x 300 mL), dried over MgSO4, and decolorized with
activated carbon. After filtration through a Gꢀ3 glass filter funnel containing Celite, the
resulting clear solution was evaporated under reduced pressure using a rotary
evaporator. Thus obtained crude product was further purified by column
chromatography on silica gel (ethylacetate/PE, 1:4)., to obtain (3b) as a pale yellow
liquid.
Yield: 23.2 g, 91 %; 1H NMR (400 MHz, CDCl3): δ = 5.20 (d,
J
= 5.1 Hz, 1H), 5.13 –
= 9.4, 6.6 Hz, 1H), 4.12 –
= 9.4, 7.6 Hz, 1H), 2.13 (s, 3H) ppm; 13C NMR (100 MHz,
5.03 (m, 1H), 4.73 (dd,
3.97 (m, 2H), 3.88 (dd,
J
J
= 13.5, 5.4 Hz, 2H), 4.15 (dd, J
CDCl3): δ = 170.23, 123.27, 120.09, 116.92, 113.74, 84.81, 80.37, 72.88, 70.80,
70.45, 20.47 ppm; IR (neat): ʋ = 3511, 2953, 2888, 1740, 1410, 1201, 1143, 1077,
970 cm–1; HRMS (ESI): MH+, found 321.0233. C9H12F3O7S requires 321.0256.
General procedure for cyanation (4a & 4c)
A 500 mL threeꢀnecked roundꢀbottom flask, equipped with a magnetic stirrer, internal
thermo couple, pressure equalizing dropping funnel and a reflux condenser, was
charged with potassium cyanide (4.0 g, 0.062 mol), 18ꢀcrownꢀ6 (16.4 g, 0.062 mol)
and dry THF (250 mL). The suspension was cooled down to between –5 oC and 0 oC,
and a solution of (3a or 3b) (10.0 g, 0.031 mol) in THF (100 mL) was added dropꢀ
wise over 1 h with stirring under a continuous flow of nitrogen. After addition was
complete, the slightly exothermic reaction was strictly maintained at the specified
temperature to avoid epimerization. The progress of the reaction was followed by
GCꢀMS analysis, which indicated that the reaction had gone to completion after 3 h.
The reaction mixture was then poured onto cold water (350 mL) and extracted with
chloroform (3 x 250 mL). The combined organic layers were dried over MgSO4 and
decolorized with activated carbon. After filtration through a Gꢀ3 glass filter funnel
containing Celite, the resulting colorless solution was evaporated under reduced
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pressure using a rotary evaporator to give the crude product. Finally, pure mono
nitrile acetates were obtained by distillation using a kugelꢀrohr glass oven to afford
(4a) as a colorless liquid and (4c) as a white crystalline solid.
General procedure for cyanation followed by epimerization (4b & 4d)
A 500 mL threeꢀnecked roundꢀbottom flask, equipped with a magnetic stirrer, internal
thermo couple, pressure equalizing dropping funnel and a reflux condenser, was
charged with potassium cyanide (4.0 g, 0.062 mol), 18ꢀcrownꢀ6 (16.4 g, 0.062 mol)
and dry THF (250 mL). The suspension was cooled down to between –5oC and 0oC,
and a solution of (3a or 3b) (10.0 g, 0.031 mol) in THF (100 mL) was added dropꢀ
wise over 1 h with stirring under a continuous flow of nitrogen. After addition was
complete, the reaction was stirred at room temperature for 1.5 h and gradually the
o
temperature was raised to 40 C which allows epimerization to take place. The
progress of the reaction was followed by GCꢀMS analysis, which indicated that the
epimerization reaction had proceeded to 65ꢀ70 % completion after 2 h. The reaction
mixture was then poured onto cold water (350 mL) and extracted with chloroform (3 x
250 mL). The combined organic layers were dried over MgSO4 and decolorized with
activated carbon. After filtration through a Gꢀ3 glass filter funnel containing Celite, the
resulting pale yellow colored solution was evaporated under reduced pressure using
a rotary evaporator to give the crude product. Finally, pure mono nitrile acetates were
obtained by distillation using a kugelꢀrohr glass oven to afford (4b) as a white solid
and (4d) as a white crystalline solid.
(3S,6S)-6-cyanohexahydrofuro[3,2-b]furan-3-yl acetate (4a)
Distillation conditions: 120 oC at 0.02 mbar for 1.5 h. Yield: 5.2 g, 85 %; 1H NMR (400
MHz, CDCl3): δ = 5.24 – 5.13 (m, 1H), 5.00 (dd,
J = 4.2, 1.8 Hz, 1H), 4.66 (d, J = 4.1
Hz, 1H), 4.16 – 3.86 (m, 4H), 3.19 (ddd, = 6.2, 5.0, 1.8 Hz, 1H), 2.09 (s, 3H) ppm;
J
13C NMR (100 MHz, CDCl3): δ = 171.69, 119.76, 88.39, 87.39, 78.87, 74.90, 72.08,
39.07, 22.68 ppm; IR (neat): ʋ = 2977, 2886, 2246, 1741, 1370, 1229, 1080, 1061,
914 cm–1; HRMS (ESI): MH+, found 198.0759. C9H12NO4 requires 198.0766.
(3S,6R)-6-cyanohexahydrofuro[3,2-b]furan-3-yl acetate (4b)
Distillation conditions: 125 oC at 0.02 for 1.5 h. Yield: 3.7 g, 60 %; m.p. 70–72 oC; 1H
NMR (400 MHz, CDCl3): δ = 5.21 (dt,
J
= 4.0, 1.3 Hz, 1H), 4.90 (t,
J
= 4.5 Hz, 1H),
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4.58 (dt,
J = 4.1, 1.0 Hz, 1H), 4.25 – 4.08 (m, 2H), 4.05 – 3.86 (m, 2H), 3.20 (ddd, J =
9.3, 7.9, 4.9 Hz, 1H), 2.09 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ = 167.81,
113.77, 85.06, 79.77, 75.57, 71.78, 67.47, 34.50, 18.82 ppm; IR (neat): ʋ = 2945,
2886, 2247, 1725, 1374, 1232, 1109, 1055, 1011, 952 cm–1; HRMS (ESI): MH+,
found 198.0754. C9H12NO4 requires 198.0766.
(3R,6S)-6-cyanohexahydrofuro[3,2-b]furan-3-yl acetate (4c)
o
Distillation conditions: 130 C at 0.02 mbar for 1.5 h. Yield: 5.6 g, 92 %; m.p. 69–71
oC; 1H NMR (400 MHz, CDCl3): δ = 5.16 (q,
4.83 (dd, = 4.9, 1.4 Hz, 1H), 4.16 (dd, = 9.1, 3.1 Hz, 1H), 4.05 (dd,
Hz, 1H), 3.96 (dd, = 10.0, 5.9 Hz, 1H), 3.86 (dd, = 10.0, 5.1 Hz, 1H), 3.21 (ddd, J
J
= 5.5 Hz, 1H), 4.88 (t,
J
= 5.2 Hz, 1H),
= 9.1, 5.9
J
J
J
J
J
= 5.9, 3.1, 1.4 Hz, 1H), 2.12 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ = 170.04,
118.01, 85.62, 81.40, 73.02, 71.06, 70.90, 37.51, 20.54 ppm; IR (neat): ʋ = 2957,
2880, 2250, 1735, 1363, 1239, 1110, 1080, 1063, 1015, 902 cm–1; HRMS (ESI):
MH+, found 198.0757. C9H12NO4 requires 198.0766.
(3R,6R)-6-cyanohexahydrofuro[3,2-b]furan-3-yl acetate (4d)
o
Distillation conditions: 130 C at 0.02 mbar for 1.5 h. Yield: 3.5 g, 57 %; m.p. 53–55
oC; 1H NMR (400 MHz, CDCl3): δ = 5.17 (q,
1H), 4.72 (t, = 5.0 Hz, 1H), 4.23 (t, = 8.1 Hz, 1H), 4.01 (t,
(dd, = 10.3, 8.5 Hz, 1H), 3.13 (ddd,
= 10.3, 7.8, 5.1 Hz, 1H), 2.13 (s, 3H) ppm; 13C
J
= 5.6 Hz, 1H), 4.82 (dd,
J = 5.8, 4.8 Hz,
J
J
J
= 5.4 Hz, 2H), 3.92
J
J
NMR (100 MHz, CDCl3): δ = 168.14, 113.20, 79.89, 79.64, 71.30, 69.49, 68.20,
34.16, 18.50 ppm; IR (neat): ʋ = 2950, 2890, 2249, 1733, 1373, 1250, 1102, 1060,
1019, 973 cm–1; HRMS (ESI): MH+, found 198.0756. C9H12NO4 requires 198.0766.
General procedure for solvolysis (5a-d)
A 250 mL oneꢀnecked roundꢀbottom flask was equipped with a magnetic stirrer and a
reflux condenser. Methanol (100 mL), HCl (37 %, 100 mL) and (4a-d) (5.0 g, 0.025
mol) were sequentially charged to the flask. After stirring at reflux temperature for 3 h,
the reaction mixture was cooled down to room temperature and extracted with
chloroform (3 x 150 mL). The combined organic layers were dried over MgSO4, and
the resulting solution was evaporated under reduced pressure using a rotary
evaporator to give the crude product. Pure (5a-d) was obtained as a colorless
viscous liquid by distillation using a kugelꢀrohr glass oven.
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(3S,6S)-methyl 6-hydroxyhexahydrofuro[3,2-b]furan-3-carboxylate (5a)
Distillation conditions: 115 oC at 0.02 mbar for 1.5 h. Yield: 4.1 g, 86 %; 1H NMR (400
MHz, CDCl3): δ = 5.04 (dd, = 4.4, 2.1 Hz, 1H), 4.46 (d, = 4.4 Hz, 1H), 4.31 (d,
3.3 Hz, 1H), 4.12 – 3.96 (m, 2H), 3.95 – 3.87 (m, 1H), 3.84 (dt, = 10.1, 1.1 Hz, 1H),
3.73 (s, 3H), 3.14 (ddd,
= 7.2, 5.1, 2.1 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ
J
J
J =
J
J
= 169.92, 86.81, 82.88, 73.87, 72.12, 68.22, 50.25, 49.65 ppm; IR (neat): ʋ = 3426,
2955, 2881, 1730, 1437, 1202, 1073, 974 cm–1; HRMS (ESI): MH+, found 189.0748.
C8H13O5 requires 189.0763.
(3R,6S)-methyl 6-hydroxyhexahydrofuro[3,2-b]furan-3-carboxylate (5b)
Distillation conditions: 125 oC at 0.02 mbar for 1.5 h. Yield: 4.0 g, 84 %; 1H NMR (400
MHz, CDCl3): δ = 4.98 (dd,
4.25 (m, 1H), 4.03 (dd, = 9.2, 5.6 Hz, 2H), 3.91 (dd,
= 10.1 Hz, 1H), 3.75 (s, 3H), 3.23 (dd,
= 5.1, 1.2 Hz, 1H), 2.81 (s, 1H) ppm; 13C
J
= 5.1, 4.0 Hz, 1H), 4.47 (dt,
J = 3.9, 1.0 Hz, 1H), 4.38 –
J
J
= 10.2, 3.5 Hz, 1H), 3.84 (d,
J
J
NMR (100 MHz, CDCl3): δ = 169.54, 89.11, 82.78 , 76.27, 75.59, 68.42, 52.05, 50.64
ppm; IR (neat): ʋ = 3431, 2953, 2885, 1733, 1439, 1206, 1080, 1007 cm–1; HRMS
(ESI): MH+, found 189.0752. C8H13O5 requires 189.0763.
(3S,6R)-methyl 6-hydroxyhexahydrofuro[3,2-b]furan-3-carboxylate (5c)
Distillation conditions: 120 oC at 0.02 mbar for 1.5 h. Yield: 3.8 g, 80 %; 1H NMR (400
MHz, CDCl3): δ = 4.85 (dd,
(m, 2H), 4.12 (dd, = 9.0, 6.7 Hz, 1H), 3.85 (d,
(dd, = 9.6, 5.6 Hz, 1H), 3.22 (ddd, = 6.3, 4.0, 1.8 Hz, 1H), 2.65 (d, J
J
= 4.9, 1.8 Hz, 1H), 4.57 (t,
= 5.7 Hz, 1H), 3.74 (s, 3H), 3.66
= 6.8 Hz, 1H).
J = 5.2 Hz, 1H), 4.34 – 4.18
J
J
J
J
ppm; 13C NMR (100 MHz, CDCl3): δ = 171.64, 85.15, 82.51, 73.61, 71.94, 71.58,
52.34, 52.16 ppm; IR (neat): ʋ = 3443, 2954, 2888, 1730, 1437, 1199, 1072, 1010
cm–1; HRMS (ESI): MH+, found 189.0754. C8H13O5 requires 189.0763.
(3R,6R)-methyl 6-hydroxyhexahydrofuro[3,2-b]furan-3-carboxylate (5d)
Distillation conditions: 115 oC at 0.02 mbar for 1.5 h. Yield: 4.0 g, 84 %; 1H NMR (400
MHz, CDCl3): δ = 4.80 (t,
6.1 Hz, 1H), 4.24 – 4.06 (m, 2H), 3.92 (dd,
(dd, = 9.4, 6.6 Hz, 1H), 3.27 (ddd,
= 10.6, 8.3, 5.3 Hz, 1H), 2.67 (br, 1H) ppm; 13C
J
= 4.8 Hz, 1H), 4.54 (dd,
J = 5.4, 4.4 Hz, 1H), 4.29 (q, J =
J
= 9.4, 6.2 Hz, 1H), 3.75 (s, 3H), 3.60
J
J
NMR (100 MHz, CDCl3): δ = 167.84, 82.02, 81.89, 73.28, 71.34, 68.67, 51.07, 50.16
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ppm; IR (neat): ʋ = 3432, 2960, 2890, 1742, 1439, 1212, 1090, 985 cm–1; HRMS
(ESI): MH+, found 189.0752. C8H13O5 requires 189.0763.
(3S,6R)-6-hydroxyhexahydrofuro[3,2-b]furan-3-carboxylic acid (6c)
A 100 mL oneꢀnecked roundꢀbottom flask equipped with a magnetic stirrer and a
reflux condenser, was charged with (5c) (1.0 g, 5.3 mmol) and aqueous HCl (3.0 M,
20 mL). The reaction mixture was stirred under reflux for 24 h and then cooled down
to room temperature. After removal of the solvent under reduced pressure using a
rotary evaporator, the crude hydroxyl carboxylic acid was subsequently recrystallized
from diethyl ether affording pure (6c) as a white solid. Single crystals were obtained
from ethanol by slow evaporation. Yield: 0.75 g, 82 % (purity: 99 %, GC analysis);
1H NMR (400 MHz, Deuterium Oxide): δ = 4.87 (dd,
5.1 Hz, 1H), 4.30 (q, = 6.1 Hz, 1H), 4.14 (dq, = 5.4, 3.3 Hz, 1H), 4.05 (dd,
6.3 Hz, 1H), 3.87 (dd, = 9.4, 5.8 Hz, 1H), 3.57 (dd, = 9.3, 6.5 Hz, 1H), 3.22 (dq, J
J
= 5.2, 2.1 Hz, 1H), 4.54 (t,
J =
J
J
J
= 9.2,
J
J
= 8.2, 2.8, 2.2 Hz, 1H); 13C NMR (100 MHz, Deuterium Oxide): δ = 175.10, 85.22,
82.24, 71.41, 71.29, 71.01, 51.99 ppm; IR (neat): ʋ = 1692 (C=O) cmꢀ1; HRꢀMS (ESI):
MH+, found 175.0601. C7H11O5 requires 175.0606.
General polymerization procedure
Stereoꢀisomer (5a-d) (0.202 g, 1 mmol) and dibutyltin oxide (DBTO) (10 mol%) was
charged into a 10 mL RB flask and inserted in to the kugelrohr oven. The setꢀup was
vented with 3 cycles of nitrogen/vacuum to remove the oxygen. During the first stage,
the reaction is carried out under nitrogen gas to form oligomers. The reaction mixture
is heated to 115 oC, and after 15 min. the catalyst dibutyltin oxide (DBTO, 10 mol%)
is added to the flask under a continuous flow of nitrogen gas. The temperature is
o
then increased to 160 C under stirring for 12 h. At this stage the reaction mixture
became opaque and solidified. Finally the temperature was raised to 180 °C for 2 h
to complete the preꢀpolymerisation reaction. In the second stage, vacuum was
o
applied gradually down to 0.02 mbar at 180 C for 2 h. The resulting polymer was
cooled down to room temperature under the continuous flow of nitrogen, dissolved in
CHCl3:TFA (6:1) mixture and precipitated into methanol, filtered and dried in vacuo at
40 oC for 15 h.
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Poly(isoidide methylcarboxylate) (PE-1)
1H NMR (400 MHz, CDCl3+TFAꢀd): δ = 5.26 (d,
Hz, 1H), 4.64 (dq, = 8.8, 4.8, 4.2 Hz, 1H), 4.05 (m, 3H), 4.04 – 3.92 (m, 1H), 3.27
(ddd,
= 6.7, 4.7, 2.0 Hz, 1H).; 13C NMR (100 MHz, CDCl3+TFAꢀd): δ = 170.80,
J
= 3.7 Hz, 1H), 5.10 (dt, J = 3.9, 1.9
J
J
86.73, 85.59, 78.73, 72.5, 70.87, 51.83 ppm; IR (neat): ʋ = 3462, 2960, 2884, 1730,
1183, 1075, 1024 cmꢀ1.
Poly(isosorbide methylcarboxylate) (PE-2)
1H NMR (400 MHz, CDCl3+TFAꢀd): δ = 5.30 (p,
J = 4.4, 3.8 Hz, 1H), 5.18 – 5.00 (m,
1H), 4.66 (h, = 4.1 Hz, 1H), 4.21 – 4.00 (m, 4H), 3.48 – 3.19 (m, 1H); δ = 166.31,
J
84.80, 81.44, 76.76, 71.52, 66.93, 48.58; IR (neat): ʋ = 3468, 2959, 2885, 1736,
1177, 1080, 1007 cmꢀ1.
Poly(isoidide-isosorbide methylcarboxylate) (PE-5)
1H NMR (400 MHz, CDCl3+TFAꢀd): δ = 5.33 (s, 1H), 5.31 – 5.25 (m, 1H), 5.22 (ddt,
J
= 7.0, 4.4, 2.0 Hz, 1H), 5.11 – 4.92 (m, 2H), 4.78 (tt, = 8.5, 3.8 Hz, 1H), 4.41 – 4.29
J
(m, 1H), 4.26 – 3.98 (m, 7H), 3.47 – 3.32 (m, 2H). δ =; IR (neat): ʋ = 3458, 2956, 2886,
1732, 1174, 1077, 1008 cmꢀ1.
Poly(isoidide-isomannide methylcarboxylate) (PE-6)
1H NMR (400 MHz, CDCl3+TFAꢀd): δ = 5.20 (dd,
Hz, 1H), 5.09 – 4.93 (m, 1H), 4.85 (dd, = 14.6, 4.9 Hz, 1H), 4.77 (d,
4.56 (dt, = 9.2, 4.6 Hz, 1H), 4.35 – 3.97 (m, 5H), 3.96 – 3.79 (m, 3H), 3.21 (ddt,
J
= 7.4, 3.7 Hz, 1H), 5.15 (t,
= 5.6 Hz, 1H),
J = 5.0
J
J
J
J =
16.6, 6.7, 3.0 Hz, 2H); IR (neat): ʋ = 3462, 2958, 2879, 1752, 1181, 1075, 1002 cmꢀ1.
Acknowledgements
Dr. A. E. Frissen and L. Gootjes, BSc. are gratefully acknowledged for NMR and
XRD analyses, W. Teunissen and H. de Beukelaer, BSc. for GCꢀMS and DSC
analyses, Dr. L. A. M. van den Broek for MALDIꢀToF measurements and E Janssen,
MSc. for HRꢀMS measurements. The Xꢀray diffractometer for the single crystal
structure determination was financed by the Netherlands Organization for Scientific
Research (NWO). This work is part of the research program of the Dutch Polymer
Institute (DPI), # 656 GREENER.
29