Four Different Regioisomeric Polycarbonates Derived from One Natural Product, d -Glucose

Article abstract of DOI:10.1021/acs.macromol.6b00591

Strategies for the preparation of polycarbonates, derived from the natural product d-glucose, which have the potential to degrade back into their bioresorbable starting material and CO₂, were developed. By employing established carbohydrate pro

Full text of DOI:10.1021/acs.macromol.6b00591

Article
pubs.acs.org/Macromolecules
Four Different Regioisomeric Polycarbonates Derived from One
Natural Product, D‑Glucose
Alexander T. Lonnecker, Young H. Lim, Simcha E. Felder, Celine J. Besset, and Karen L. Wooley*
́
Departments of Chemistry, Chemical Engineering, and Materials Science & Engineering, and Laboratory for Synthetic-Biologic
Interactions, Texas A&M University, College Station, Texas 77842, United States
S
* Supporting Information
ABSTRACT: Strategies for the preparation of polycarbonates,
derived from the natural product D-glucose, which have the
potential to degrade back into their bioresorbable starting
material and CO2, were developed. By employing established
carbohydrate protection/deprotection chemistries, two D-
glucose derivatives, methyl 4,6-O-benzylidene-α-D-glucopyra-
noside or methyl α-D-glucopyranoside, were converted into
four different regioisomeric diol monomers, i.e., 1,4-, 1,6-, 2,6-,
or 3,6-diols, as confirmed by nuclear magnetic resonance
(NMR) spectroscopy, infrared (IR) spectroscopy, and mass
spectrometry. Each type of regioisomeric monomer was then
employed in a condensation polymerization with phosgene,
generated in situ from triphosgene, as a comonomer, in the presence of pyridine, to produce four types of polycarbonates with
different backbone regio-connectivity, as characterized by size exclusion chromatography, NMR spectroscopy, and IR
spectroscopy. Interestingly, their thermal properties, i.e., glass transition temperature (Tg) and thermal degradation behavior,
were tunable by changing the topological composition of the monomeric unit. That is, polycarbonates with 2,6- and 3,6-
backbone connectivity resulted in significantly higher Tg of ca. 85 and 83 °C, respectively, as compared to those with 1,4- and 1,6-
backbone connectivity, showing a Tg of ca. 33 °C, as measured by differential scanning calorimetry. Furthermore, when the
thermal decomposition temperature was measured by thermogravimetric analysis, the nonanomeric carbon backbone-based
polycarbonates (2,6- and 3,6-) exhibited higher thermal stability and a sharper decomposition profile, with onset decomposition
temperature (Td,onset) at 363 or 336 °C, as compared with those polymers containing the anomeric carbon in the carbonate
linkage (1,4- and 1,6-), having Td,onset at 171 and 163 °C.
rials, we have a keen interest in expanding these systems to
include new natural resources, such as cyclitols,21,22 mono-
saccharides,23 terpenes,24,25 and menthides,26,27 as starting
materials for monomer synthesis to produce polymers that are
capable of degrading into bioresorbable products.21,22,28,29
Among different types of natural products applicable to
polymeric systems, one of our foci is in saccharides that can be
transformed into polycarbonates, for potential use in the field of
orthopedic tissue engineering, which has been limited to simple
variations on conventional systems, including aliphatic
polyesters, poly(hydroxy acids), and polyanhydrides.30−34
Previously, several elegant works reported polycarbonates
composed of monosaccharides, often with the saccharide
moiety as a side chain substituent,35−37 an opened ring in the
main chain of copolymers,38−40 or an intact saccharide ring in
the polymer backbone.41−46 In addition, much interest has been
devoted to modified saccharide feedstocks,42,47,48 allowing for
facile synthetic strategies as well as the generation of high-
INTRODUCTION
■
The past few decades have seen a paradigm shift in the
development of polymeric materials, from nondegradable to
degradable constructs, for medical and related applications,1−3
but also for environmental and sustainability impact. Examples
of biomedically relevant degradable polymeric materials vary
widely from their potential utility as sutures and orthopedic
devices to engineered tissues and drug delivery systems.1,4−6
The major driving force for exploiting degradable polymeric
materials for use in biomedical applications is concerns
associated with their long-term biocompatibility in the human
body.7,8 For instance, artificial implants with nondegradable
materials may necessitate follow-up procedures, i.e., their
replacement or removal, and nondegradable drug delivery
carriers may elicit translational issues regarding in vivo fate,
clearance, accumulation, and possible toxicity.3,6,9
Creating the next generation of biomaterials, new mono-
meric systems need to be explored to achieve improved
functionality, degradability, and biocompatibility.5,10 While our
group has reported several promising nanoscopic constructs
derived from degradable precursors, e.g., polyphosphoest-
ers,11−17 polypeptides,18,19 and polycarbonates,20 as biomate-
Received: March 22, 2016
Revised: August 29, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.macromol.6b00591
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trifluoromethanesulfonate (TMSOTf), trimethylamine (TEA),
tetrabutylammonium iodide (TBAI), magnesium sulfate (MgSO4),
sodium sulfate (Na2SO4), sodium hydroxide (NaOH), sodium
bisulfate (NaHSO4), sodium bicarbonate (NaHCO3), phosgene
(20% solution in toluene), diphosgene, and triphosgene were
purchased from Sigma-Aldrich Company. Unless noted, all reagents
were used as received. Dichloromethane (DCM), tetrahydrofuran
(THF), N,N-dimethylformamide (DMF), and toluene were purified
and dried by passage through a solvent purification system (J.C. Meyer
Solvent Systems). Monomers 4, 8, 11, and 12 were dried under
reduced pressure over P2O5 and stored under argon environment.
Likewise, all polymer samples, 13, 14, 15, and 16, were dried over
P2O5 under reduced pressure overnight prior to characterizations.
Synthesis of Glucose Monomer 4. Synthesis of Methyl 2,3-Di-
O-benzyl-4,6-O-benzylidene-α-D-glucopyranoside (2). Methyl 4,6-O-
benzylidene-α-D-glucopyranoside, 1 (12.4 g, 43.9 mmol), KOH (14.7
g, 262 mmol), and BnBr (45.1 g, 264 mmol) were suspended in 200
mL of toluene and heated to reflux. Water generated in situ was
collected by a Dean−Stark apparatus. The reaction was monitored by
thin layer chromatography (TLC) until complete consumption of
starting material was observed, and the reaction mixture was then
allowed to cool to room temperature. The mixture was washed with
water and the aqueous layer was extracted with DCM. The organic
layer was dried with MgSO4 and concentrated under vacuum. The
residue was then purified by column chromatography on silica gel,
eluting with a 85:15 mixture of hexane and acetone, resulting in a
white solid (18.7 g, 92.0% yield). FTIR (ATR): 3100−3000, 3950−
2800, 1450, 1367, 1329, 1175, 1084, 1050, 1028, 964, 732, 692, 652
cm−1. 1H NMR (500 MHz, CDCl3, ppm): δ 7.59−7.26 (b, 15H), 5.62
(s, 1H), 4.99 (d, J = 11.0 Hz, 1H), 4.93 (d, J = 2.5 Hz, 1H), 4.91(d, J =
2.0 Hz, 1H), 4.77 (d, J = 12.5 Hz, 1H), 4.68 (d, J = 4.0 Hz, 1H), 4.34
(dd, J = 5.0 Hz, J = 10.0 Hz, 1H), 4.13 (t, J = 9.5 Hz, 1H), 3.90 (td, J =
5.0 Hz, J = 9.5 Hz, 1H), 3.77 (t, J = 10.0 Hz, 1H), 3.68 (t, J = 9.5 Hz,
1H), 3.63 (dd, J = 4.0 Hz, J = 9.5 Hz, 1H), 3.47 (s, 3H). 13C NMR
(125 MHz, CDCl3, ppm): δ 138.8, 138.2, 137.5, 129.1−127.5 (m),
126.1, 101.3, 99.3, 82.2, 79.3, 78.7, 75.4, 73.8, 69.1, 62.4, 55.4. +ESI
MS: calculated [M + Li]+ for C28H30O6: 469.2202; found: 469.2191.
Synthesis of Methyl 2,3,6-Tri-O-benzyl-α-D-glucopyranoside (3).
Compound 2 (14.8 g, 32.0 mmol) was suspended in 500 mL of THF
under N2 atmosphere, and NaBH3CN (14.5 g, 230 mmol) was added.
After stirring for 45 min at room temperature, the temperature was
decreased to 0 °C, and AlCl3 (38.4 g, 288 mmol) was added.
Following an additional hour of stirring, the reaction mixture was
filtered to remove the aluminum salts. The filtrate was extracted with
500 mL of DCM and washed with water. The aqueous phase was
extracted with DCM, and the organic layers were combined, dried with
Na2SO4, and then concentrated under vacuum. The residue was
purified by column chromatography on silica gel, eluting with a 7:3
mixture of hexane and ethyl acetate, to produce a colorless oil (12.6 g,
84.8% yield). FTIR (ATR): 3600−3250, 3100−3000, 2950−2800,
performing engineering polymers. With our interest in
developing engineering-type polymeric materials that are
synthesized from and can undergo hydrolytic degradation
into natural products,49 we have explored strategies for the
transformation of carbohydrates into polycarbonates, using
cellulose as a model structure with replacement of enzymati-
cally cleavable glycosidic linkages by hydrolytically labile
carbonates.
Herein, we investigated the synthesis of polycarbonates built
from D-glucose, an abundant natural product that is prevalent
both in nature and the human body, to afford a unique family of
biosourced, potentially degradable, engineering polymers:
poly(D-glucose carbonates) (PGCs). It is noteworthy that
glucose is an important carbohydrate, acting as an energy
source, a metabolic intermediate, and a monomeric repeat unit
in many natural polymeric support structures.50 Starting from
derivatives of this appealing starting material, we employed
established carbohydrate protection and deprotection chem-
istries to prepare four types of linear PGCs with different
regioisomeric backbone connectivities and evaluated the effect
of backbone connectivity on their thermal properties.
EXPERIMENTAL SECTION
■
Instrumentation. 1H, 13C, and COSY NMR spectra were recorded
on a Varian Inova 500 spectrometer. Chemical shifts were referenced
to the solvent resonance signals. The data obtained were processed
and analyzed using MestReNova software.
IR spectra were recorded on a Shimadzu IR Prestige attenuated
total reflectance Fourier transform infrared spectrophotometer (ATR-
FTIR) and analyzed using IRsolution v. 1.40 software.
Size exclusion chromatography (SEC) measurements were
performed on a Waters Chromatography, Inc. (Milford, MA), system
equipped with an isocratic pump model 1515, a differential
refractometer model 2414, and a four-column set of 5 μm Guard
(50 × 7.5 mm), Styragel HR 4 5 μm DMF (300 × 7.5 mm), Styragel
HR 4E 5 μm DMF (300 × 7.5 mm), and Styragel HR 2 5 μm DMF
(300 × 7.5 mm) using DMF (0.05 M LiBr) as the eluent (1.00 mL/
min) at 70 °C. Polymer solutions were prepared at a concentration of
ca. 3−5 mg/mL, and an injection volume of 200 μL was used. Data
collection and analysis were performed with Empower 2 v. 6.10.01.00
software (Waters, Inc.). The system was calibrated with polystyrene
standards (Polymer Laboratories, Amherst, MA) ranging from 615 to
442 800 Da.
Glass transition temperatures (Tg) were measured by differential
scanning calorimetry (DSC) on a Mettler-Toledo DSC822 (Mettler-
Toledo, Inc., Columbus, OH) under N2, with a heating rate of 10 °C/
min. Measurements were analyzed using Mettler-Toledo Stare v.10.00
software. The Tg was taken as the midpoint of the inflection tangent,
upon the third heating scan. Thermogravimetric analysis (TGA) was
performed under an Ar atmosphere using a Mettler Toledo model
TGA/SDTA851e apparatus with a heating rate of 10 °C/min that was
coupled to a Pfeiffer ThermoStar/GSD320T3 mass spectrometer. Ions
generated during TGA ranging from 0 to 300 amu were detected over
a span of 30 s (10 ms/amu) during the run of the TGA with a steady
flow of Ar (10 mL/min). TGA and mass spectrometry data were
analyzed using Mettler-Toledo Stare v.10.00 and Pfeiffer QUADERA
software, respectively. Column chromatography was performed on a
Combiflash Rf+ (Teledyne ISCO) with RediSep Rf Columns
(Teledyne ISCO).
1
1720, 1703, 1452, 1047, 910, 735, 696 cm−1. H NMR (500 MHz,
CDCl3, ppm) δ: 7.48−7.28 (b, 15H), 5.05 (d, J = 12.0 Hz, 1H), 4.81
(dd, J = 7.5 Hz, J = 11.0 Hz, 2H), 4.70 (overlapping, 2H), 4.61 (q, J =
12.0 Hz, 2H), 3.85 (t, J = 9.5 Hz, 1H), 3.80−3.70 (overlapping, 3H),
3.66 (t, J = 9.5 Hz, 1H), 3.59 (dd, J = 10.0 Hz, J = 3.5 Hz, 1H), 3.43 (s,
3H). 13C NMR (125 MHz, CDCl3, ppm): δ 138.9, 138.1, 128.9−127.3
(m), 98.2, 81.5, 79.7, 75.5, 73.6, 73.2, 70.7, 70.0, 69.5, 55.3. +ESI MS:
calculated [M + Li]+ for C28H32O6: 471.2359; found: 471.2365.
Synthesis of 2,3,6-Tri-O-benzyl-D-glucopyranoside (4). Com-
pound 3 (3.944.0 g, 8.48 mmol) was dissolved in 75 mL of AcOH
at room temperature. The solution was heated to 110 °C, and 40 mL
of HCl (4 N) was added. The reaction was monitored by TLC and
stopped after 35 min. The reaction mixture was added to 500 mL of
water and neutralized by the addition of 2 M NaOH. The solution was
extracted with 500 mL of DCM. The organic layer was dried with
Na2SO4 and concentrated under vacuum. The residue was purified by
chromatography on silica gel, eluting with a 7:3 mixture of hexane and
ethyl acetate, and then concentrated under vacuum. The product was
recrystallized in a 7:1 mixture of hexanes and ethyl acetate resulting in
1.22 g (32.1% yield) of 4, which was used without further purification.
Materials. Aluminum chloride (AlCl3), acetic anhydride (Ac2O),
acetic acid (AcOH), benzyl bromide (BnBr), borane−tetrahydrofuran
complex (1.0 M in THF, BH3·THF), methyl α-D-glucopyranoside,
methyl 4,6-O-benzylidene-α-D-glucopyranoside, potassium hydroxide
(KOH), sodium cyanoborohydride (NaBH3CN), sodium hydride
(NaH, 60% suspension in mineral oil), concentrated sulfuric acid
(conc H2SO4), anhydrous methanol (MeOH), sodium methoxide
solution (25 wt % in methanol, NaOMe in MeOH), trimethylsilyl-
B
DOI: 10.1021/acs.macromol.6b00591
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FTIR (ATR): 3500−3300, 3100−3000, 2950−2800, 1498, 1453,
2800, 1452, 1362, 1232, 1213, 1145, 1085, 1062, 1028, 989, 731, 694
cm−1. 1H NMR (500 MHz, CDCl3, ppm): δ 7.43−7.30 (b, 30H), 5.26
(d, J = 3.5 Hz, 1H), 5.06−4.66 (broad overlapping, 13H), 4.11 (t, J =
9.0 Hz, 1H), 4.06 (m, 1H), 3.94−3.84 (m, 2H), 3.76−3.65
(overlapping, 3H), 3.62−3.43 (overlapping, 5H). 13C NMR (125
MHz, CDCl3, ppm): δ 138.7, 138.5, 138.4, 138.0, 137.9, 128.8−127.2
(m), 97.3, 91.0, 84.5, 83.3, 81.6, 80.1, 77.9, 76.0−74.6 (m), 73.1, 71.1,
62.0. +ESI MS: calculated [M + Li]+ for C27H30O6: 457.2202; found:
457.2217.
1
1337, 1216, 1132, 1101, 1048, 1024, 910, 865, 755, 695 cm−1. H
NMR (500 MHz, CDCl3, ppm): δ 7.44−7.28 (b, 15H), 5.26 (d, J =
3.5 Hz, 1H), 5.04 (d, J = 11.5 Hz, 1H), 4.82 (d, J = 11.5 Hz, 1H), 4.75
(dd, J = 17.2 Hz, J = 12.5 Hz, 2H), 4.60 (dd, J = 22.0 Hz, J = 12.0 Hz,
2H), 4.06 (m, 1H), 3.88 (t, J = 9.0, 2H), 3.76−3.66 (m, 2H), 3.64−
3.55 (overlapping, 2H) ppm. 13C NMR (125 MHz, CDCl3, ppm): δ
138.7, 137.9, 128.8−127.4, 91.2, 81.2, 79.7, 75.4, 73.6, 72.9, 70.9, 70.0,
69.7 ppm. +ESI MS: calculated [M + Li]+ for C27H30O6: 457.2202;
found: 457.2195.
Synthesis of D-Glucose-Derived Monomers 11 and 12.
Synthesis of Methyl 3-O-Benzyl-4,6-O-benzylidene-α-D-glucopyra-
noside (9) and Methyl 2-O-Benzyl-4,6-O-benzylidene-α-D-glucopyr-
anoside (10). Methyl 4,6-O-benzylidene-α-D-glucopyranoside (1)
(10.2 g, 36.1 mmol), BnBr (10.5 g, 61.4 mmol), and tetrabutyl-
ammonium hydrogen sulfate (2.53 g, 7.44 mmol) were dissolved in
600 mL of DCM. To this solution, 50 mL of 5% NaOH (aq) was
added, and the mixture was heated to reflux for 26 h. The mixture was
separated, and the aqueous layer was extracted with 50 mL of DCM.
The organic layers were combined, dried with MgSO4, filtered, and
concentrated under reduced pressure. The resulting residue was
purified by column chromatography eluting with a gradient of hexane
and ethyl acetate to afford methyl 3-O-benzyl-4,6-O-benzylidene-α-D-
glucopyranoside 9 (7.61 g, 56.6%) and methyl 2-O-benzyl-4,6-O-
benzylidene-α-D-glucopyranoside 10 (5.42 g, 40.3%) as white solids.
Methyl 3-O-Benzyl-4,6-O-benzylidene-α-D-glucopyranoside (9).
FTIR (ATR): 3500−3100, 3100−3000, 2980−2800, 1450, 1366,
1211, 1172, 1136, 1070, 1056, 1028, 991, 968, 935, 922, 898, 735, 695,
650 cm−1. 1H NMR (500 MHz, CDCl3, ppm): δ 7.57−7.26 (b, 10H),
5.61 (s, 1H), 5.01 (d, J = 11.5 Hz, 1H), 4.84 (d, J = 12.5 Hz, 2H), 4.34
(dd, J = 10.5 Hz, 4.0 Hz, 1H), 3.93−3.83 (overlapping, 2H), 3.83−
3.73 (overlapping, 2H), 3.68 (t, J = 9.5 Hz, 1H), 3.48 (s, 3H). 13C
NMR (125 MHz, CDCl3, ppm): δ 138.6, 137.4, 129.2−125.8 (m),
101.3, 100.0, 82.0, 78.9, 74.9, 72.5, 69.0, 62.6, 55.4. +ESI MS:
calculated [M + H]+ for C21H24O6: 373.1651; found: 373.1652.
Methyl 2-O-Benzyl-4,6-O-benzylidene-α-D-glucopyranoside (10).
FTIR (ATR): 3600−3200, 3100−3000, 2950−2800, 1720, 1454,
1379, 1359, 1273, 1197, 1147, 1076, 1026, 962, 921, 748, 698, 678,
Synthesis of Glucose Monomer 8. Synthesis of Methyl 2,3,4,6-
Tetra-O-benzyl-α-D-glucopyranoside (6). NaH (60% suspension in
mineral oil, 41.3 g, 1.72 mol) was washed with hexane under N2.
Hexane was removed in vacuo, and NaH was suspended in DMF (600
mL). Methyl α-D-glucopyranoside (21.0 g, 0.108 mmol) was added
over 45 min to the stirring reaction mixture at 0 °C and was left for 4
h. TBAI (3.85 g, 10.4 mmol) was added, followed by the dropwise
addition of BnBr (83.2 g, 486 mmol). The reaction mixture was
allowed to warm to room temperature and stirred for 20 h. To quench
the reaction, H2O (100 mL) was added dropwise over 20 min. The
mixture was extracted with DCM and washed with brine. The organic
layers were collected, dried with MgSO4, filtered, and concentrated
under reduced pressure. The resulting residue was purified by column
chromatography on silica gel, eluting with 7:3 mixture of hexane and
ethyl acetate, to yield the benzylated product (47.9 g, 80.0% yield).
FTIR (ATR): 3550−3300, 3100−3000, 2975−2800, 1740, 1452,
1
1360, 1155, 1088, 1070, 1044, 1028, 912, 735, 700 cm−1. H NMR
(500 MHz, CDCl3, ppm): δ 7.46−7.20 (b, 20H), 5.10−4.52 (b, 9H),
4.08 (t, J = 9.0 Hz, 1H), 3.86−3.78 (overlapping, 2H), 3.75−3.69
(overlapping, 2H), 3.65 (dd, J = 9.5, J = 3.5 Hz, 1H), 3.46 (s, 3H)
ppm. 13C NMR (125 MHz, CDCl3, ppm): δ 138.9, 138.3, 138.2,
138.0, 128.8−127.4 (m), 98.3, 82.2, 79.9, 77.8, 76.0−73.2 (m), 70.2,
68.6, 55.2 ppm. +ESI MS: calculated [M + Li]+ for C35H38O6:
561.2828; found: 561.2835.
Synthesis of Acetyl 2,3,4-Tri-O-benzyl-6-acetyl-D-glucopyrano-
side (7). Compound 6 (5.47 g, 9.85 mmol) was dissolved in a solution
of AcOH/Ac2O (1:1, 50 mL). The solution was cooled to 0 °C while
stirring. Concentrated H2SO4 (1 mL) was added dropwise. After
stirring for 1 h, 50 mL of sataturated NaHCO3 and 50 mL of cold
distilled H2O were added sequentially. The aqueous solution was
extracted with DCM. The collected organic layers were washed with
brine, dried with MgSO4, filtered, and concentrated. The resulting
residue was purified by column chromatography on silica gel, eluting
with a gradient of hexane and ethyl acetate to yield the product 7 as an
oil (3.31 g, 62.9% yield). FTIR (ATR): 3100−3000, 2975−2825,
1742, 1497, 1454, 1369, 1227, 1150, 1066, 1010, 933, 735, 695 cm−1.
1H NMR (500 MHz, CDCl3, ppm): δ 7.43−7.27 (b, 15H), 6.38 (d, J =
3.5 Hz, 1H), 5.05 (d, J = 11.0 Hz, 1H), 4.95 (d, J = 11.0 Hz, 1H), 4.89
(d, J = 11.0 Hz, 1H), 4.76 (d, J = 11.5 Hz, 1H), 4.69 (d, J = 11.5 Hz,
1H), 4.64 (d, J = 11.0 Hz, 1H), 4.36−4.28 (m, 2H), 4.04 (t, J = 9.0 Hz,
1H), 4.02−3.98 (m, 1H), 3.73 (dd, J = 9.5 Hz, J = 3.5 Hz, 1H), 3.63
(dd, J = 9.5 Hz, J = 1.0 Hz, 1H), 2.20 (s, 1H), 2.07 (s, 1H). 13C NMR
(125 MHz, CDCl3, ppm): δ 170.7, 169.4, 138.5, 137.6, 137.5, 127.5−
128.9 (m), 89.7, 81.7, 78.9, 76.6, 75.8, 75.3, 73.3, 71.1, 62.7, 21.1, 20.9.
+ESI MS: calculated [M + Li]+ for C31H34O8: 541.2414; found:
541.2427.
Synthesis of 2,3,4-Tri-O-Benzyl-D-glucopyranoside (8). Com-
pound 7 (1.99 g, 3.73 mmol) was weighed in a flame-dried 50 mL
Schlenk flask under N2 atmosphere. Anhydrous THF (24 mL) and
anhydrous MeOH (8 mL) were added sequentially, and the solution
was stirred at 0 °C. After addition of NaOMe solution (25% in
MeOH) dropwise, the reaction mixture was allowed to stir for 40 min.
The reaction was neutralized by adding NaHSO4 (1 M) and saturated
NaHCO3. After adding ethyl acetate (100 mL), the reaction mixture
was washed with distilled H2O (75 mL) and brine (75 mL), dried with
MgSO4, filtered, and concentrated. The resulting residue was purified
by column chromatography on silica gel, eluting with a gradient of
hexane and ethyl acetate, to yield the product 8 (1.58 g, 93.8% yield),
which was observed by 1H NMR spectroscopy as a 1:1 mixture of the
α and β isomers in CDCl3. FTIR (ATR): 3600−3100, 3028, 2990−
1
660, 617 cm−1. H NMR (500 MHz, CDCl3, ppm): δ 7.56−7.32 (b,
10H), 5.54 (s, 1H), 4.81 (d, J = 12.0 Hz, 1H), 4.72 (d, J = 12.5 Hz,
1H), 4.64 (d, J = 3.5 Hz, 1H), 4.29 (dd, J = 10.0 Hz, J = 5.0 Hz, 1H),
4.18 (t, J = 9.5 Hz, 1H), 3.84 (td, J = 10.0 Hz, J = 5.0 Hz, 1H), 3.72 (t,
J = 10.5 Hz, 1H), 3.55−3.47 (overlapping, 2H), 3.40 (s, 3H). 13C
NMR (125 MHz, CDCl3, ppm): δ 138.0, 137.2, 129.5−126.0 (m),
102.0, 98.7, 81.3, 79.6, 73.4, 70.3, 69.0, 62.1, 55.4. +ESI MS: calculated
[M + H]+ for C21H24O6: 373.1651; found: 373.1655.
Methyl 3,4-Di-O-benzyl-α-D-glucopyranoside (11). To a solution
of 9 (0.824 g, 2.21 mmol) in 22 mL of anhydrous DCM, in a flame-
dried round-bottom Schlenk flask with 3 Å molecular sieves, was
added BH3·THF complex (1.0 M in THF, 11.0 mL, 11.0 mmol) and
TMSOTf (0.100 mL, 0.550 mmol) under a N2 atmosphere. After 90
min, the reaction was quenched by addition of 10 mL of methanol and
1.5 mL of TEA. The solution was filtered, concentrated, evaporated
with 50 mL of methanol three times, and then purified by column
chromatography on silica gel, eluting with a gradient of hexane and
ethyl acetate, to yield 11 as a white solid as a white solid (0.691 g,
83.5% yield). FTIR (ATR): 3525−3225, 3100−3000, 2950−2775,
1500, 1452, 1358, 1329, 1206, 1142, 1093, 1059, 1026, 901, 760, 731,
692 cm−1. 1H NMR (500 MHz, CDCl3, ppm): δ 7.45−7.28 (m, 10H),
4.97 (d, J = 11.0 Hz, 1H), 4.92 (q, J = 5.5 Hz, 2H), 4.77 (d, J = 4.0 Hz,
1H), 4.71 (d, J = 11.0 Hz, 1H), 3.87−3.80 (overlapping, 2H), 3.77
(dd, J = 12.0 Hz, J = 4.0 Hz, 1H), 3.74−3.68 (overlapping, 2H), 3.59
(t, J = 9.5 Hz, 1H), 3.44 (s, 3H). 13C NMR (125 MHz, CDCl3, ppm):
δ 138.6, 138.1, 128.9−127.3 (m), 99.4, 83.0, 77.3, 75.4, 75.0, 73.0,
71.1, 61.7, 55.2. + ESI MS: calculated [M + Li]+ for C21H26O6:
381.1889; found: 381.1898.
Methyl 2,4-Di-O-benzyl-α-D-glucopyranoside (12). To a solution
of 10 (2.05 g, 5.50 mmol) in 60 mL of DCM, in a flame-dried round-
bottom Schlenk flask with 3 Å molecular sieves was added BH3·THF
complex (1.0 M in THF, 28.0 mL, 28.0 mmol) and TMSOTf (0.25
mL, 1.38 mmol) under a N2 atmosphere. After 90 min the reaction
C
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Scheme 1. Synthesis of D-Glucose-Based Diol Monomers 4, 8, 11, and 12
was quenched by addition of 30 mL of methanol and 3 mL of TEA.
The solution was filtered, concentrated, evaporated with 75 mL of
methanol three times, and then purified by column chromatography
on silica gel, eluting with a gradient of hexane and ethyl acetate, to
yield 12 as a white solid (1.73 g, 84.1% yield). FTIR (ATR): 3400−
3150, 3100−3000, 2975−2775, 1454, 1367, 1192, 1101, 1065, 1028,
Poly(D-glucose)3,6 Carbonate, 16. SEC: Mw = 21 000 g/mol, Mn =
15 000 g/mol, Đ = 1.40. FTIR (ATR): 3100−2800, 1753, 1454, 1369,
1238, 1070, 1041, 1028, 999, 905, 781, 736, 696, 605 cm−1. 1H and 13
C
NMR spectra are attached in the Supporting Information, Figures S37
and S38. DSC: Tg,midpoint = 83 °C. TGA in Ar: 379 °C, 82% mass loss;
18% mass remaining above 379 °C.
1
993, 901, 841, 732, 694, 636 cm−1. H NMR (500 MHz, CDCl3,
ppm): δ 7.42−7.28 (b, 10H), 4.95 (d, J = 11.0 Hz, 1H), 4.73 (d, J =
11.0 Hz, 2H), 4.67 (d, J = 13.0 Hz, 1H), 4.62 (d, J = 4.0 Hz, 1H), 4.15
(t, J = 9.0 Hz, 1H), 3.80 (dd, J = 12.0 Hz, J = 2.5 Hz, 1H), 3.73 (dd, J
= 11.5 Hz, J = 4.5 Hz, 1H), 3.66 (td, J = 10.0 Hz, J = 3.0 Hz, 1H), 3.50
(t, J = 9.5, 1H), 3.38 (dd, J = 9.5 Hz, J = 3.5 Hz, 1H), 3.34 (s, 3H). 13C
NMR (125 MHz, CDCl3, ppm): δ 138.3, 137.9, 127.4−128.8 (m),
97.5, 79.7, 77.2, 74.5, 73.3, 73.0, 70.4, 61.7, 55.1. +ESI MS: calculated
[M + Li]+ for C21H26O6: 381.1889; found: 381.1881.
RESULTS AND DISCUSSION
Based upon our overall goal of producing engineering types of
polymers that are modeled from cellulose, derived from
■
Table 1. Conditions and Results of the Experimental Design
for the Copolymerizations of Monomer 4 and Carbonylation
Agents (Phosgene, Diphosgene, or Triphosgene)
General Procedure of Polycondensation Using D-Glucose-
Derived Monomers, 4, 8, 11, or 12, and Triphosgene.
Triphosgene was added to a cold solution (0 °C) of the appropriate
diol in anhydrous pyridine at a concentration of 400 mg/mL under a
N2 atmosphere. The reaction was allowed to stir for 5 min and then
warmed to RT and allowed to react for 48 h. The reaction was then
quenched with a saturated solution of Na2CO3 (ca. 2 mL) until no
further evolution of carbon dioxide was observed. The residue was
diluted with dichloromethane; the organic layer was washed with 10%
aqueous HCl and then dried over MgSO4, filtered, and concentrated
under reduced pressure.
c
concn
carbonylation
agent
equiv of
duration
(h)
Mp
a
b
expt (g/L)
carbonylation agent
(Da)
1
2
3
4
5
6
7
8
9
200
400
600
phosgene
1
2
3
3
1
2
2
3
48
72
24
72
24
48
24
48
72
9000
5500
5600
8800
5600
8700
5600
5600
6600
diphosgene
triphosgene
phosgene
diphosgene
triphosgene
phosgene
diphosgene
triphosgene
Poly(D-glucose)1,4 Carbonate, 13. SEC: Mw = 5500 g/mol, Mn =
1
5000 g/mol, Đ = 1.13. FTIR (ATR): 3100−3000, 3000−2750, 1759,
1
1454, 1364, 1246, 1099, 989, 894, 735, 695 cm−1. H and 13C NMR
a
b
Concentration of 4 in pyridine. Number of equivalents of
carbonylation agents vs 4. Peak average molecular weight determined
c
spectra are included in the Supporting Information, Figures S31 and
S32. DSC: Tg,midpoint = 33 °C. TGA in Ar: 267 °C, 15% mass loss; 345
°C, 74% mass loss; 26% mass remaining above 345 °C.
by SEC-DMF for crude polymers vs polystyrene standards.
Poly(D-glucose)1,6 Carbonate, 14. SEC: Mw = 4800 g/mol, Mn =
4400 g/mol, Đ = 1.09. FTIR (ATR): 3100−3000, 3000−2800, 1755,
1454, 1356, 1248, 1070, 1026, 1001, 735, 696 cm−1. 1H and 13C NMR
spectra are attached in the Supporting Information, Figures S33 and
S34. DSC: Tg,midpoint = 33 °C. TGA in Ar: 294 °C, 22% mass loss; 367
°C, 74% mass loss; 26% mass remaining above 367 °C.
Poly(D-glucose)2,6 Carbonate, 15. SEC: Mw = 32 100 g/mol, Mn =
19 200 g/mol, Đ = 1.67. FTIR (ATR): 3100−3000, 3000−2800, 1747,
1454, 1361, 1338, 1246, 1126, 1047, 1001, 785, 735, 696 cm−1. 1H and
13C NMR spectra are attached in the Supporting Information, Figures
S35 and S36. DSC: Tg,midpoint = 85 °C. TGA in Ar: 397 °C, 82% mass
loss; 18% mass remaining above 397 °C.
glucose, yet capable of undergoing hydrolytic degradation
without the requirement of cellulase enzymes, we initially
designed a 1,4-diol monomer of glucose and then expanded the
scope to other regioisomeric glucose diol analogues. It was
hypothesized that a series of glucose-derived diols could be
copolymerized with a carbonylation agent to afford a series of
regioisomeric polycarbonates. The series of poly(D-glucose
carbonate)s were designed to mimic certain aspects of cellulose
and glycogen. The 1 → 4-β-D-glycosidic linkages of cellulose
facilitate chain packing to create crystallinity and provide for
D
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series of monomers and corresponding polymers having 1,4-,
1,6-, 2,6-, and 3,6-regiochemistries were investigated.
Table 2. Effect of Each Factor Evaluated by Placket−Burman
Experiment (y = Average of Each Factor)
̂
Synthesis of Four Regioisomeric Diols from D-
Glucose. Starting from commercially available protected
glucose compounds, methyl 4,6-O-benzylidene-α-D-glucopyr-
anoside (1) or methyl α-D-glucopyranoside (5), four different
regioisomeric monomers 4, 8, 11, and 12, having 1,4-, 1,6-, 2,6-,
and 3,6-diols, respectively, were prepared through three
synthetic routes (Scheme 1). The structure of each compound
conditions
y
̂
effect
concn (g/L)
200
6690
7710
5920
−80
930
400
600
−850
duration (h)
1
was thoroughly characterized by H, 13C, and COSY NMR
24
5580
7800
6950
−1200
1020
170
48
spectroscopies, IR spectroscopy, and high-resolution mass
spectrometry (HR-MS). All relevant NMR and IR spectra are
included in the Supporting Information (Figures S1−S52).
Synthesis of 1,4-Diol Monomer, 2,3,6-Tri-O-benzyl-D-
glucopyranoside, 4. In the first step, protection of two
hydroxyl groups at the C2 and C3 positions of methyl 4,6-O-
benzylidene-α-D-glucopyranoside (1) with benzyl groups
afforded the completely protected glucose derivative, methyl
2,3-di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranoside (2).
Selective benzylidene ring-opening, using NaBH3CN and
AlCl3, was then performed to give a free hydroxyl group at
C4 as the major product in ca. 85% yield. Ring-opening of the
benzylidene was confirmed by the complete disappearance of
the 1H NMR resonance at 5.62 ppm and the 13C NMR
resonance peak at 101.3 ppm, corresponding to the acetal
methine in the starting material. Finally, demethylation at C1 of
methyl 2,3,6-tri-O-benzyl-α-D-glucopyranoside (3) under acidic
conditions resulted in the desired monomer 4 in ca. 32% yield,
after column chromatography and recrystallization in a solution
72
equiv of carbonylation agent
1
2
7050
6600
6670
280
−170
−100
3
carbonylation agent
phosgene
diphosgene
triphosgene
7780
5550
6990
1010
−1230
220
Scheme 2. Polymerization of Four Regioisomeric Diols, 4, 8,
11, and 12, with Phosgene, Generated in Situ from
Triphosegene, as a Comonomer and Pyridine as a Base
1
of hexane and ethyl acetate. Interestingly, single H and 13C
NMR resonance peaks at 5.26 and 91.2 ppm, respectively, for
the anomeric carbon, C1, appeared in the NMR spectra, despite
the potential formation of two isomers, α and β, generated
during acidic treatment.
Synthesis of 1,6-Diol Monomer, 2,3,4-Tri-O-benzyl-D-
glucopyranoside, 8. Initially, attempts to prepare methyl
2,3,4,6-tetra-O-benzyl-α-D-glucopyranoside, 6, were made by
following a similar synthetic strategy to 4, that is, protection of
the two hydroxyl groups at C2 and C3, selective ring-opening
of the benzylidene, followed by demethylation of the hydroxyl
group at C1. However, isolation of the desired product during
the final demethylation step with methyl 2,3,4-tri-O-benzyl-α-D-
glucopyranoside was challenging, and thus, an alternate strategy
was chosen. First, benzylation of methyl-α-D-glucopyranoside
(5) was conducted in the presence of NaH, BnBr, and a
catalytic amount of TBAI in DMF to give methyl 2,3,4,6-tetra-
O-benzyl-α-D-glucopyranoside (6) in ca. 80% yield. Simulta-
neous removal of the methyl and benzyl protecting groups at
C1 and C6, respectively, was performed in a one-pot manner by
acid-catalyzed acetolysis, as described by Gervay-Hague et al.,55
resulting in 1,6-diacetate compound 7 in ca. 63% yield.
Conversion from methyl and benzyl substituents at C1 and
C6, respectively, to acetyl groups at both positions was
appropriate mechanical properties.51 The crystallinity also
contributes to the relative hydrolytic stability and its need of
enzymatic catalysis for degradation.52 Unlike glucose, glycogen,
connected by linear α-1,4- and 1,6-repeat units as well as
branching 1,4,6-repeat units, does not share the same hydrolytic
stability and mechanical strength. In contrast to the relative
stability of the 1,4-glycosidic linkages of cellulose, 1,4-carbonate
connectivity of the glucose repeat units was expected to reduce
hydrolytic and thermal stability due to the carbonate linkage
being through a hemiacetal functionality of the anomeric
site.53,54 With proper understanding of structure−property
relationships with regards to various regiochemistries of
possible glucose monomers, a polymer system with the ability
to fulfill a myriad of applications can be developed. Therefore, a
1
confirmed by disappearance of the H NMR signal of the
methyl group resonating at 3.46 ppm and the 13C NMR
resonance at 55.2 ppm, coincident with the appearance of
acetyl 1H NMR resonances at 3.76−3.65 (3Hs) and 3.62−3.43
(3Hs) and 13C NMR resonances at 170.7, 169.4, 21.1, and 20.9
ppm. Compound 7 was then converted to the 1,6-diol
monomer, 2,3,4-tri-O-benzyl-D-glucopyranoside (8) in near-
quantitative yield, ca. 94%, upon deprotection using NaOMe in
MeOH. The collected product 8 was observed as a mixture
(1:1) of α and β isomers, as demonstrated by the occurrence of
E
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Table 3. Results of Polymerization Using Four Regioisomeric Monomers 4, 8, 11, and 12 To Afford 13, 14, 15, and 16,
Respectively
a
a
monomer
solvent
duration (h)
equiv of triphosgene
equiv of pyridine
[M]
Mn (Da)
Mw (Da)
Đ
4
DCM
DCM
DCM
DCM
DCM
DCM
DCM
1,4-dioxane
DCM
DCM
DCM
DCM
DCM
DCM
DCM
bulk
1
5
0.40
0.46
0.40
0.40
0.33
0.33
0.33
0.33
0.33
0.33
0.33
0.33
0.50
0.50
0.33
0.50
0.33
0.33
2.5
4.2
4.7
3.8
2.0
4.0
4.0
4.0
4.0
4.0
2.0
4.0
2.0
4.0
4.0
4.0
4.0
4.0
0.56
0.57
0.26
0.12
1.0
5000
6200
5500
6700
1.13
1.08
1.09
1.16
1.20
1.16
1.09
1.03
1.22
1.25
1.37
1.67
1.06
1.36
1.20
1.34
1.40
1.19
24
1
7800
8500
8
5700
6600
24
24
24
24
1
5900
7000
0.50
1.0
7100
8200
4400
4800
1.0
5085
5250
11
0.50
0.50
0.50
0.50
0.50
0.50
0.50
-
12400
15500
38000
19200
17000
42000
25000
28400
15000
21200
15100
19400
52000
32100
18000
57000
30100
38000
21000
25300
12
24
24
24
24
48
24
24
72
12
DCM
DCM
0.50
0.50
a
Molecular weight determined by SEC-DMF for crude polymers vs polystyrene standards.
near 1:1 ratio. Then, their conversion to monomers 11 and 12,
respectively, was performed by selective benzylidene ring-
opening with TMSOTf and BH3 THF complex in high yields
ca. 84%. The benzylidene ring-opening was confirmed by the
1
complete disappearance of H NMR singlet resonances at 5.61
and 5.54 ppm and 13C NMR resonances at 101.3 and 102.0
ppm corresponding to the acetals of compounds 9 and 10,
respectively. Furthermore, HR-MS analysis confirmed the
formation of two isomeric compounds 11 and 12, resulting
in an identical molecular weight of 381 m/z (381.1898 and
381.1881, respectively, with Li in a positive mode).
Preparation of D-Glucose-Derived Polymers with
Different Backbone Regiochemistries. Screening of
Polymerization Conditions Using Diol Monomer 4. Screening
for appropriate polycondensation conditions was performed
using 4, which could generate a polycarbonate analogue of
cellulose, having 1,4-backbone connectivity. Initial efforts were
focused on employing alternative carbonylation reagents to
phosgene, such as diphenyl, di-p-nitrophenyl, dimethyl, and
diethyl carbonates. However, it was observed that these
conditions were either too harsh, causing degradation of the
starting material, or not conducive to forming large molecular
weight polymers, as monitored by NMR spectroscopy or SEC.
The reaction duration, monomer concentration, and the
quantity of phosgene analogues, i.e., phosgene, diphosgene, or
triphosgene, were tested by a Plackett−Burman experimental
design (matrix 43, where 4 is the number of factors and 3 is the
number of levels tested for each factor) based on nine
experimental conditions (Table 1, experiments 1−9) conducted
on scales of 150 mg of monomer in the volume of solvent
needed to give the three desired monomer concentrations
(combined pyridine and toluene (in the case of phosgene
reagent)).21,56 This study of the effects of individual factors
indicated that PGCs with the highest molecular weights could
be produced under polymerization conditions that included a
monomer concentration of 400 g/L, phosgene and triphosgene
as carbonylation agents at a stoichiometry of one molar
equivalence (Table 2). However, phosgene was precluded from
further study because of its instability and safety concerns
Figure 1. SEC traces of representative polymers of 13, 14, 15, and 16.
Table 4. Summary of Thermal Properties of PGCs 13, 14,
15, and 16, Measured by DSC and TGA
polymer
Tg (°C)
Td1,onset (°C)
Td2,onset (°C)
13
14
15
16
33
33
85
83
171
163
363
336
267
294
13C NMR resonance peaks at 97.3 and 91.0 ppm from the C1
anomeric carbon. Finally, HR-MS measurement demonstrated
the presence of compound 8 as an isomeric form of compound
4, having the identical molecular weight of 457 m/z (457.2217,
with Li in a positive mode).
Synthesis of Methyl 3,4-Di-O-benzyl-α-D-glucopyranoside,
11, and Methyl 2,4-Di-O-benzyl-α-D-glucopyranoside, 12.
The other two diol monomers 11 and 12 were derived from 1
as a single, common starting material. Specifically, benzylation
of the two hydroxyl groups at C2 and C3 using the bulky phase
transfer agent TBAH led to two separable isomers, 9 and 10, in
F
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Figure 2. Differential scanning calorimetry analysis of 13 (a), 14 (b), 15 (c), and 16 (d). The Tg values determined from the heating cycles are
confirmed by the cooling cycles.
associated with its use. Still, use of the more stable and more
conveniently handled triphosgene led to 1,4-PGC’s having
comparable molecular weights.
IR spectra (Figures S49−S52). Furthermore, a significant
reduction in intensity of broad OH stretches in the IR spectra
from each diol monomer to the corresponding PGC supported
1
Synthesis of Four Regioisomeric PGCs. Using the
conditions from the polymerization optimization study, four
regioisomeric polymers, 13, 14, 15, and 16, were synthesized
from each diol monomer, 4, 8, 11, and 12, respectively
(Scheme 2). Varying conditions, such as polymerization time,
amount of triphosgene and pyridine, and monomer concen-
tration, were also examined to determine their effects on
molecular weight and molecular weight distributions (or
dispersity, Đ) of the resulting PGCs by SEC analysis (Table
3 and Figure 1). Interestingly, copolymerization of 4 or 8,
having an active hydroxyl at the anomeric position, with
triphosgene resulted in 13 and 14 with limited molecular
weight, below 8 kDa, whereas copolymerization of 11 and 12
led to 15 and 16 with significantly higher Mn, above 10 kDa, in
all of our attempts. Most of the SEC traces were monomodal,
and their distributions were heavily dependent on polymer
molecular weight. In general, Đ increased with higher molecular
weight polymers, which is typical of polycondensations.
Formation of the carbonate backbone linkages upon
polymerization was directly observed by the introduction of a
13C NMR signal at 150 ppm and was also confirmed by the
appearance of a single absorbance band at ca. 1750 cm−1 in the
the polymerization event as well as the broadening of the H
NMR signals.
Thermal Properties of the Prepared Regioisomeric
PGCs. In the following studies, the thermal properties of the
prepared polymers with four backbone regioconnectivities were
examined by DSC and TGA analyses. All four polymers 13, 14,
15, and 16 exhibited amorphous behavior, and interestingly, the
regiochemistry of the polymer backbone appeared to play an
important role in determining the glass transition temperature,
Tg, of the polymers (Table 4 and Figure 2). Both 13 and 14
contained the anomeric carbon in the carbonate backbone, and
displayed lower Tg values, ca. 33 °C, than 15 and 16, ca. 85 and
83 °C, respectively. As we described previously, 13 and 14 are a
mixture of stereoisomers, α and β, at the anomeric carbon,
which could hinder the chain−chain packing in the final
polymers. In contrast, both 15 and 16 are composed of a single
isomeric backbone structure, with equatorial linkages coming
from the glucose rings and may allow for better chain−chain
packing and require higher energy for long-chain segmental
motion as compared to 13 and 14. Although a key factor
influencing the Tg could be the difference in the stereo-
chemistries of the regioisomers, the molecular weights of 13
G
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Figure 3. Thermogravimetric analysis of 13 (a), 14 (b), 15 (c), and 16 (d).
Scheme 3. Thermal Degradation Pathways for 13 Based on Tandem TGA-MS Analysis
H
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and 14 were significantly lower than those of 15 and 16, and
polymer molecular weight is well-known to influence Tg below
the (Tg)∞. In addition, the differences in methyl vs benzyl
protecting groups, with 13 and 14 having three benzyl groups
whereas 15 and 16 contain two benzyl and one methyl
protecting groups, could increase the free volume and
contribute to the decrease in Tg values for 13 and 14.
Different regiochemistries in the polymer backbone also had
a significant impact on the thermal stabilities of the polymers.
The two polymers 15 and 16, not incorporating the anomeric
position into the polymer backbone, behaved like rigid
polymers, exhibiting high thermal stability and a sharp
decomposition profile, with onset decomposition temperature,
respectively, as compared to those with 1,4- and 1,6-backbone
connectivities each giving polymers with a Tg of 33 °C. Finally,
in the study of thermal stability, the nonanomeric backbone-
based PGCs exhibited high thermal stabilities and sharp
decomposition profiles, with Td,onset, of 336 or 363 °C as
compared with PGCs containing the anomeric carbon in the
carbonate linkage, having Td1,onset of 171 and 163 °C and
Td2,onset of 267 and 294 °C, respectively. Fundamental studies
to understand the influence of the anomeric carbon as part of
the polycarbonate backbone on other physical and chemical
properties, including the hydrolytic stabilities, are currently
under investigation. Furthermore, study of the mechanical
properties of glucose-based polycarbonates is underway.
Td,onset, at 363 and 336 °C, respectively (Table 4 and Figure 3).
Meanwhile, as predicted, polymers with the carbonate linkage
connected through the anomeric center showed much lower
thermal stabilities. For example, 13 had two different Td,onset
values, with the first onset, Td1,onset, appearing at 171 °C and the
second, Td2,onset, at 267 °C. Similarly, 14 had Td1,onset at 163 °C
and Td2,onset.d at 294 °C. Neighboring functionality can have an
effect on the thermal stability of a carbonate group. Initially, it
was proposed that the endocyclic oxygen in the glucose ring
was playing a role in the thermal degradation, similar to
previously reported carbonate sugars,53,54 accelerating the
decomposition of the backbone. Tandem TGA-MS of polymer
13 detected peaks in increments of m/z 44, which could be
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.macro-
mol.6b00591.
■
S
Figures S1−S52 (PDF)
Additional characterization data (TXT)
AUTHOR INFORMATION
Corresponding Author
*E-mail: wooley@chem.tamu.edu (K.L.W.).
Notes
■
+.
attributed to the loss of CO2 . However, the mass loss that
occurred during the first phase of degradation was too great to
be attributed to the loss of only CO2. In addition, several other
peaks were also observed early in the decomposition of the
polymer at increments of m/z 77, 91 and 92, as well as 105 and
106, which corresponded to phenyl, toluyl, and benzoyl
radicals, respectively. Possible mechanistic pathways for the
thermal degradation that led to the observed products from 13
are illustrated in Scheme 3.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge financial support from the National
Science Foundation through CHE-1410272, as well as the
National Science Foundation Graduate Research Fellowship
(S.E.F.). The Welch Foundation is gratefully acknowledged for
support through the W. T. Doherty-Welch Chair in Chemistry,
Grant No. A-0001.
CONCLUSIONS
■
In conclusion, we report the design, synthesis, and thermal
characterization of four types of polycarbonates, constructed
from D-glucose derivatives, having different backbone regioche-
mistries. By employing established carbohydrate protection and
deprotection chemistries, two D-glucose derivatives, methyl 4,6-
O-benzylidene-α-D-glucopyranoside or methyl α-D-glucopyra-
noside, were converted into four regioisomeric diol monomers
having 1,4-, 1,6-, 2,6-, or 3,6-diols with reasonably high yields
>80%, in most cases. Characterizations of each compound by
NMR, IR, and mass spectrometry confirmed the reliability of
our synthetic approach. After optimizing the polymerization
conditions, the reactivity of each synthesized monomer was
examined through a condensation polymerization with
phosgene, generated in situ from triphosgene, as a comonomer
in the presence of pyridine, resulting in the generation of four
polycarbonates having different backbone regioconnectivities.
The copolymerizations of monomers, where neither of the
active hydroxyl groups are at the anomeric center, 2,6- or 3,6-
diols, allowed for the production of PGCs with high molecular
weights, >10 kDa. However, only small molecular weight
PGCs, <8 kDa, were generated with monomers having an
active hydroxyl group at the anomeric center, 1,4- or 1,6-diols.
Interestingly, monomer regiochemistry appeared to be the
crucial parameter influencing the thermal properties of the
polymers. PGCs with 2,6- and 3,6-backbone connectivity
resulted in significantly higher Tg materials, 85 and 83 °C,
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