Poly(lactic acid) polymer stars built from early generation dendritic polyols

Article abstract of DOI:10.1139/cjc-2012-0471

A family of polymer stars has been prepared from early generation dendritic cores with four, six, and eight arms. Four dendritic cores were prepared from the sequential reaction of a multifunctional alcohol with a protected anhydride, followed by deprotection to afford two or three new alcohol functionalities per reactive site. These cores were used as initiators for the tin-catalyzed ring-opening polymerization of l-lactide and rac-lactide to afford isotactic and atactic degradable stars, respectively. Two series of stars were prepared for each monomer, either maintaining total molecular weight or number of monomer units per arm. The polymers were characterized by NMR spectroscopy, light-scattering gel-permeation chromatography, differential scanning calorimetry, and thermogravimetric analysis. Our results support previous work that suggests that the length of the arms dictates thermal properties rather than the total molecular weight of the star. Little effect was noted between aromatic and aliphatic cores, presumably due to the flexibility of the rest of the core molecule. We have shown that early generation dendrimers can serve as excellent core structures for building core-first polymer stars via the ring-opening of cyclic esters.

Full text of DOI:10.1139/cjc-2012-0471

392
ARTICLE
Poly(lactic acid) polymer stars built from early generation dendritic
polyols
Genny E. Keefe, Jean-d'Amour K. Twibanire, T. Bruce Grindley, and Michael P. Shaver
Abstract: A family of polymer stars has been prepared from early generation dendritic cores with four, six, and eight arms. Four
dendritic cores were prepared from the sequential reaction of a multifunctional alcohol with a protected anhydride, followed by
deprotection to afford two or three new alcohol functionalities per reactive site. These cores were used as initiators for the
tin-catalyzed ring-opening polymerization of L-lactide and rac-lactide to afford isotactic and atactic degradable stars, respectively.
Two series of stars were prepared for each monomer, either maintaining total molecular weight or number of monomer units
per arm. The polymers were characterized by NMR spectroscopy, light-scattering gel-permeation chromatography, differential
scanning calorimetry, and thermogravimetric analysis. Our results support previous work that suggests that the length of the
arms dictates thermal properties rather than the total molecular weight of the star. Little effect was noted between aromatic and
aliphatic cores, presumably due to the flexibility of the rest of the core molecule. We have shown that early generation
dendrimers can serve as excellent core structures for building core-first polymer stars via the ring-opening of cyclic esters.
Key words: poly(lactic acid), dendrimer, biodegradable polymer, synthesis, star polymer, thermal properties, DSC, TGA.
Résumé : On a préparé une famille de polymères en étoile a` partir de cœurs dendritiques de premières générations possédant
quatre, six ou huit branches. On a produit quatre cœurs dendritiques en partant de la réaction séquentielle d'un alcool
multifonctionnel avec un anhydride protégé, suivie d'une déprotection de manière a` donner deux ou trois nouvelles fonctions
alcool par site de réaction. Ces cœurs ont servi d'initiateurs de polymérisation par ouverture de cycle, catalysée par l'étain, du
L-lactide et du rac-lactide pour obtenir des étoiles dégradables de formes isotactique et atactique, respectivement. Pour chaque
monomère, on a préparé deux séries d'étoiles, en maintenant le même poids moléculaire total ou le même nombre d'unités
monomériques par branche. On a caractérisé les polymères par spectrométrie RMN, par chromatographie par perméation de gel
associée a` un détecteur a` diffusion de lumière, par calorimétrie différentielle a` balayage (DSC) et par analyse thermogravimé-
trique (ATG). Nos résultats corroborent ceux de travaux antérieurs donnant a` penser que la longueur des branches dicte les
propriétés thermiques plutôt que le poids moléculaire total de l'étoile. Nous n'avons constaté que peu de différence entre les
cœurs aromatiques et aliphatiques, probablement en raison de la flexibilité du reste de la molécule centrale. Nous avons montré
que les dendrimères de premières générations peuvent constituer d'excellentes structures de base pour la construction de
polymères en étoile a` partir du cœur par ouverture d'esters cycliques. [Traduit par la Rédaction]
Mots-clés : acide polylactique, dendrimère, polymère biodégradable, synthèse, polymère en étoile, propriétés thermiques, DSC,
ATG.
increased number of chain-end functionalities and the improved
control over degradation have promoted these structures as alter-
Introduction
Control over polymer macrostructure, especially over polymer
natives to linear poly(lactic acid) in biomedical and nanotechnol-
topology, is an increasingly important method to modify polymer
ogy applications.7–10 Thermal properties are also affected, with
properties. These branched structures include graft, comb, brush,
lower glass transition, melting, and crystallization temperatures
cross-linked, dendritic, and star polymer topologies.1–3 Of partic-
observed when compared with linear polymers of the same mo-
ular interest, star polymers possess multiple arms connecting at a
lecular weight.11 The effect of tacticity on these systems is also
central core to form a globular core-shell macrostructure with
increased chain-end density and short linear segments.4 The stars
can be synthesized through two methods. The arm-first approach
uses pre-synthesized linear polymers that are attached onto a
central core through either a coupling strategy or the addition of
a bifunctional comonomer terminator.5 The core-first approach is
complementary, and arguably offers a more systematic variation
of core composition and control over the number of arms.6 This
route exploits a multifunctional initiator from which polymer
arms are grown.
profound, with significant changes in thermal properties and deg-
radation observed in concert with their more extensively ex-
plored linear counterparts.6,7 The nature of the core in polymer
stars has also been previously studied; in particular, examining
the number of arms and molecule rigidity.12
In parallel with the development of star polymer topologies,
dendritic systems have seen explosive growth in research and
applications. These repetitively branched molecules can offer
even higher numbers of end-group functionalities and modified
properties.13 They are traditionally difficult to synthesize to high
molecular weights and generations, but have found important
Our particular interest in this field is in the preparation of
polymer stars of aliphatic polyesters such as poly(lactic acid). The
Received 29 November 2012. Accepted 12 January 2013.
G.E. Keefe. Department of Chemistry, University of Prince Edward Island, 550 University Avenue, Charlottetown, PEI C1A 4P3, Canada.
J.-d'.K. Twibanire and T.B. Grindley. Department of Chemistry, Dalhousie University, 6274 Coburg Road, Halifax, NS B3H 4R2, Canada.
M.P. Shaver. Department of Chemistry, University of Prince Edward Island, 550 University Avenue, Charlottetown, PEI C1A 4P3, Canada; School of Chemistry, University of Edinburgh,
Edinburgh, Scotland EH9 3JJ, United Kingdom.
Corresponding author: Michael P. Shaver (e-mail: michael.shaver@ed.ac.uk).
Can. J. Chem. 91: 392–397 (2013) dx.doi.org/10.1139/cjc-2012-0471
Published at www.nrcresearchpress.com/cjc on 25 January 2013.

Keefe et al.
393
Scheme 1. (A) Tacticity-controlled polymerization of lactide. (B) Dendritic polyol cores used in star-shaped PLA synthesis.
Scheme 2. Formation of tetraol 4.
applications from drug and gene delivery to sensor technol-
ogy.13,14 We were interested in merging these two fields and ex-
amining early-generation dendritic cores as potential initiators
for poly(lactic acid) polymer stars. This work presents the use of
four dendritic polyols as novel nontoxic cores for the synthesis of
stars with 4, 6, and 8 arms with both L- and rac-lactide as feed-
stocks to generate isotactic and atactic arms (Scheme 1). Two te-
traols differentiated by the presence of aromatic or aliphatic
backbones at the dendrimer cores were targeted. Two families are
examined, investigating stars of similar molecular weights and
similar arm lengths, respectively.
Results and discussion
The desired early generation polyester dendrimers were synthe-
sized using standard techniques.15 The aryl-substituted tetraol 4,
was prepared by reaction of 1,4-bis-(2-hydroyethoxy)benzene 1,16
with 2.4 equiv of anhydride 2,17 followed by deprotection, as
shown in Scheme 2. Repetition of the reaction sequence extended
compound 4 to the second generation polyester dendrimer: the
octaol 6 as shown in Scheme 3. The same anhydride reaction and
deprotection steps were also used to convert 1,8-octanediol 7 into
the first generation tetraol 9, as shown in Scheme 4. The final
core, hexaol 11, was prepared according to procedures found in
the literature (Scheme 5).16
screening reactions, which also confirmed that the differences
observed were a result of changes to core structure rather than
slight deviations in molecular weights. The polymerization data
for these experiments, producing four series of polymer stars, are
shown in Table 1, with further details provided in the Supplemen-
tary data (supporting information). Molecular weights were deter-
mined by GPC, and the number of monomer units per PLA arm
was calculated from the Mn value, correcting for the nature of the
core initiator.
Polymer stars with each of the four cores were synthesized
using Sn(Oct)2 as a catalyst for the ring-opening polymerization of
cyclic esters. Using rac- or L-lactide as the feedstock produced atac-
tic or isotactic polymer stars, respectively. While ring-opening
polymerizations catalyzed by Sn(Oct)2 are usually conducted in
solution at 70 °C to minimize transesterification reactions, the
low solubility of initiators 4, 6, 9, and 11 led to inefficient initia-
tion and broad polydispersities (PDIs) under these conditions.
Lower PDIs were obtained by performing the polymerizations un-
der an inert atmosphere in neat, molten lactide at 120 °C for
30 min or less. Longer reaction times led to lowered molecular
weights and increased PDIs, while shorter times led to variability
in molecular weights. Reaction times were tuned by multiple
Series 1 and 2 stars were prepared from isopure L-lactide with
high levels of control. Series 1 represents a family of stars with
similar overall molecular weights (29.5–32.4 kDa), while Series 2
attempted to produce a family of stars with similar arm lengths
(49–54 lactic acid units per arm). Although PDIs of 1.07 or less
were maintained, in all instances a small amount of low molecu-
lar weight homopolymer was observed in the GPC traces (<2% of
the total sample mass), characteristic of some self-initiation reac-
tions. Purification of the material by reprecipitation removed the
low molecular weight impurities.
Similarly, Series 3 and 4 were prepared from rac-lactide, equiv-
alent to Series 1 and 2, respectively, with similar overall molecular
weights and arm lengths. The equimolar mixture of D- and
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394
Can. J. Chem. Vol. 91, 2013
Scheme 3. Elaboration of tetraol 4 into octaol 6.
Scheme 4. Formation of first generation dendrimer 9 from 1,8-octanediol.
Scheme 5. Preparation of hexaol 11.16
polymer stars by 1H NMR spectroscopy indicated complete initia-
tion of all alcohol sites, as supported by the disappearance of
CH2–OH resonances.
Table 1. Polymerization data for poly(lactic acid) polymer stars using
four dendritic initiators.
Monomer
units/arm
Our premise in starting this work was that the early-generation
dendritic cores could capably function as foundation pieces for
polymer star synthesis. We also wished to explore the relation-
ship between star molecular weight, arm length, and thermal
properties in these systems. Differential scanning calorimetry
and thermogravimetric analysis accessed glass (Tg), crystallization
(Tc), melting (Tm), and decomposition (Td) temperatures for these
systems. The data for the L-lactide stars are provided in Table 2.
As is characteristic for these semi-crystalline materials, Tg, Tc,
and Tm temperatures are all observed. Matching what is often
observed in linear poly(lactic acid)s, two melting peaks are pres-
ent (see Fig. 1), although only the largest of these two peaks is
tabulated below, owing to inadequate resolution of the smaller
peak. For the stars of similar total mass (Table 2, Series 1), an
increase in arm number resulted in lowered melting tempera-
tures for stars of similar total molecular weight: a trend that
supports previous reports from the literature.18 Melting tempera-
tures for stars with arms of similar lengths (Table 2, Series 2) were
noticeably consistent, with the exception of 2–4, suggesting that
arm length is an important factor in determining the Tm. With
stars of similar total mass, enhancement of Tc with increasing
number of arms was observed, indicating that a decrease in mo-
lecular weight of the individual PLA arms corresponds to a higher
Tc. The opposite trend was seen for stars of similar arm length,
with crystallization occurring at a lower temperature for the stars
with a greater number of arms. Hence, the lower total molecular
weight stars had a higher Tc, demonstrating that Tcs are depen-
dent on both the total star molecular weight and the molecular
weight of each individual arm. No discernable trends were ob-
served in Tgs, except for a remarkable consistency in the data for
the stars of similar arm length. This is consistent with the Tm data,
a
Series
1
Monomer
Initiator
Mn
PDI
L-LA
L-LA
L-LA
L-LA
L-LA
L-LA
L-LA
L-LA
rac-LA
rac-LA
rac-LA
rac-LA
rac-LA
rac-LA
rac-LA
rac-LA
4 (4-arm)
11 (6-arm)
6 (8-arm)
9 (4-arm)
4
11
6
9
4
11
6
9
4
11
6
32400
29500
32100
29600
32400
43100
61200
29600
30800
30600
29200
29300
30800
47000
58500
29300
1.17
1.01
1.01
1.02
1.07
1.02
1.03
1.02
1.39
1.18
1.09
1.31
1.39
1.25
1.29
1.31
54
34
27
50
54
49
52
50
53
36
22
50
53
53
50
50
2
3
4
9
Note: Polymerizations conducted at 120 °C in neat molten lactide for 15, 20, or
30 min to high conversion with variable feedstock ratios of core:catalyst:lactide
(see also supplementary data, Table S1).
aMolecular weights determined using GPC with a light-scattering detector
using a dn/dc value for poly(lactic acid) of 0.051.
L-lactide produces an atactic chain, as Sn(Oct)2 offers no tacticity
control over the reaction. Increased polydispersities (up to 1.39)
were noted for these amorphous materials relative to the semic-
rystalline stereoregular material in Series 1 and 2, although only
monomodal traces were observed, and no transesterification re-
action products found by MALDI–TOF MS. The oligomeric mate-
rial observed in Series 1 and 2 was not observed, and is assumed to
be too low to be quantified by GPC (Supplementary data, Figs. S1
and S2). In all instances for Series 1–4, characterization of the
Published by NRC Research Press

Keefe et al.
395
Table 2. Thermal properties of isotactic polymer stars of
similar total molecular weight and similar arm molecu-
lar weight.
Table 3. Thermal properties of atactic polymer
stars of similar total molecular weight and similar
arm molecular weight.
Series
Core
Tg (°C)
Tc (°C)
Tm (°C)
Td (°C)
Series
Core
Tg (°C)
Td (°C)
1
1
1
4
11
6
9
4
11
6
9
52.3
53.5
52.1
52.3
52.3
52.2
52.4
52.3
94.2
95.7
96.5
88.7
94.2
85.0
84.5
88.7
160.1
152.6
147.2
158.8
160.1
158.4
158.4
158.8
240.0
250.0
249.2
247.9
240.0
239.0
240.5
247.9
3
3
3
3
4
4
4
4
4
11
6
9
4
11
6
9
43.8
40.8
37.4
39.8
43.8
33.8
42.9
39.8
273.4
279.7
279.2
277.3
258.3
279.2
295.4
277.2
1
2
2
2
2
Note: DSC conditions: 50 mL min−1 N2 purge flow, heating/
Note: DSC conditions: 50 mL min−1 N2 purge flow, heat-
ing/cooling rate of 5 °C min−1, heat/cool/heat cycle. TGA
conditions: 60 mL min−1 N2 sample purge flow, heating
rate of 10 °C min−1, decomposition temperature measured
at point of fastest weight loss.
cooling rate of 5 °C min−1, heat/cool/heat cycle. TGA conditions:
60 mL min−1 N2 sample purge flow, heating rate of 10 °C min−1
,
decomposition temperature measured at point of fastest weight
loss.
Fig. 1. Example from differential scanning calorimetry (1–11).
generally very similar, with the phase transition temperature for
the flexible core slightly lower.
Conclusions
The effects of core structure and polymer arm tacticity on poly-
(lactic acid) star polymer properties were investigated via the syn-
thesis and characterization of four series of polymer stars.
Tacticity was shown to have important implications on the phase
transition and degradation temperatures of these stars, as has
been observed in previous studies involving both linear and star-
shaped polymers. To fully discern the consequences of changing
the number of arms in such polymers, stars of similar total mo-
lecular weight as well as stars of similar arm molecular weight
were synthesized with each of the four dendritic polyol initiators.
The isotactic stars in particular showed some interesting trends in
the phase transition temperatures. These Tms and Tgs showed
reliance on individual arm length. The crystallization tempera-
tures, however, showed dependence on both arm molecular
weight and total molecular weight, with lower weights corre-
sponding to a higher transition temperature. The nature of the
core backbone was also explored as a possible factor in the deter-
mination of star properties, and little difference between ali-
phatic and aromatic cores was observed. This study supported the
utility of dendritic polyol cores in polymer star synthesis, suggest-
ing that star size, and thus bioactive loading, can be easily altered
with higher dendrimer generations without affecting overall
polymer properties. In addition, it provided clear lessons in cata-
lyst choice, suggesting that robust aluminum catalysts can offer
better control in macromolecular synthesis. We will continue to
develop our interest in dendritic cores as frameworks for building
aliphatic stars in the future, further investigating the relationship
between chemical composition and star arms on polymer
properties.
which suggests that arm length is crucial in controlling phase
transition temperatures.
The nature of the core, the length of the arms, and the number
of arms had little correlation with the decomposition properties
of the PLA star polymers. Tds are reported at the point of fastest
weight loss, which was also when the material had lost approxi-
mately 50% of its total weight. For isotactic stars, Td values ranged
from 239–250 °C, with complete degradation occurring by 397 °C
in all instances. Significant differences in these thermal transi-
tions were noted, however, for the atactic stars. These data are
shown in Table 3.
As expected, atactic poly(lactic acid) stars lacked crystallization
and melting peaks. The amorphous polymers had Tgs that were
significantly lower than for the isotactic stars, in agreement with
previous studies on tacticity-controlled star polymers and linear
PLA. While no apparent trends were evident for stars of similar
arm length (Table 3, Series 4), Series 3 again showed that an in-
crease in the number of arms corresponded to a slight lowering of
Tg values, which may be attributable to modest differences in
polymer dispersity. Previous studies have demonstrated the asso-
ciation of PDI with Tg, with increased polymerization control cor-
responding to lower Tg values.2 Tds were higher than for the
isotactic samples, although onset and maximum decomposition
temperatures were similar.
Experimental
Materials and general methods
HPLC-grade THF was purchased from Caledon Laboratory
Chemicals and deuterated solvents were purchased from Cam-
bridge Isotopes. Tin(II) ethylhexanoate was purchased from
Sigma–Aldrich and distilled under reduced pressure prior to use.
Purasorb rac-lactide and L-lactide purchased form PURAC Bioma-
terials were purified by sublimation under vacuum three times
prior to use. Dichloromethane was refluxed over calcium hydride
and distilled onto molecular sieves. MeOH was also dried over
calcium oxide and distilled over molecular sieves. Pyridine was
dried over potassium hydroxide and was stored over molecular
sieves. Unless otherwise noted, non-aqueous reactions were carried
out under a nitrogen atmosphere. Compounds were visualized/
located by spraying the TLC plate with a solution of 2% ceric ammo-
Finally, the comparison of aromatic and aliphatic backbones is
possible by comparing samples from core 9 and core 4. The nature
of the backbone appeared to have little effect on the thermal
properties of the polymer stars studied. The differential scanning
calorimetry (DSC) and thermogravimetric analysis (TGA) data col-
lected for the atactic and isotactic stars with cores 9 and 4 were
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396
Can. J. Chem. Vol. 91, 2013
nium sulfate in 0.5 mol/L H2SO4, followed by heating on a hot plate
until color developed.
(s, 4H, PhH); 13C{1H} NMR (125.7 MHz, CDCl3) ␦ 174.2 (2 C=O), 153.1,
115.9 (PhC), 98.1 (C-2), 66.7 (PhOCH2), 66.0 (C-4, C-6), 63.2
(CH2OC=O), 41.9 (Cquat), 24.6 (CH3eq), 22.8 (CH3ax), 18.7 (CH3). HR EI
MS: m/z calculated for C26H38NaO10: 533.2357. Found 533.2371.
1H NMR spectra of polymeric materials were collected using a
300 MHz Bruker Avance Spectrometer. 1H and 13C{1H} NMR spec-
tra of core molecules were recorded on a 500 MHz NMR spectrom-
eter operating at 500.13 and 125.7 MHz respectively using the
solvent resonances as secondary standards. Coupling constant (J)
values are reported in Hz. High-resolution mass spectra were re-
corded using electrospray ionization with a time of flight mass
analyzer. Melting points are uncorrected. All syntheses involving
air-sensitive compounds were performed under an inert nitrogen
atmosphere in an MBraun LABmaster sp glovebox. GPC analyses
were performed with a Polymer Laboratories PL-GPC 50 plus sys-
tem equipped with 2 × 7.8 mm DVB Jordi gel columns and a Wyatt
MiniDawn light scattering detector. HPLC-grade THF was used to
dissolve and elute the samples (flow rate: 1 mL min−1) at 50 °C.
Thermogravimetric analyses were either performed on a TA In-
struments TGA Q500 under nitrogen with balance and purge
flow rates of 40 mL min−1 and 60 mL min−1 and a heating rate of
10 °C min−1 or on a Thermo-Microbalance TG 209 F3 Tarsus instru-
ment under an argon atmosphere, using a flow rate of 60 mL
min−1 and a heating rate of 10 °C min−1. Differential scanning
calorimetry was carried out using a TA Instruments DSC Q100
with hermetically sealed aluminum pans. A flow rate of 50 mL
min−1 was used and a heat (200 °C)/cool (–50 °C)/heat (200 °C) cycle
was employed with heating and cooling rates of 5 °C min−1.
1,4-Bis-(2-(2,2-bis(hydroxymethyl)propanoyloxy)ethoxy)benzene (4)
Compound 3 (1.50 g, 2.94 mmol) was deprotected as described
above in the general procedure for the removal of isopropylidene
acetals to give the title compound 4 as colourless crystals (1.24 g,
1
98% yield). H and 13C{1H} NMR data match previously reported
data.16
1,4-Bis-(2-(2,2-bis((2,2,5-trimethyl-1,3-dioxan-5-yl)
methanoyloxymethyl)propanoyloxy)-ethoxy)benzene (5)
Compound 4 (0.650 g, 1.51 mmol), dry pyridine (10 mL), CH2Cl2
(30 mL), DMAP (0.162 g, 1.33 mmol) and anhydride 2 (2.40 g,
7.26 mmol) were stirred at room temperature for 5 h under ni-
trogen. After work up and purification as described above, the
product was obtained as a colourless crystalline solid (1.50 g, 94%
yield); mp 110–112 °C; 1H NMR (500.13 MHz, CDCl3) ␦ 1.12 (s, 12H, 4
CH3), 1.30 (s, 6H, 2 CH3), 1.34 (s, 12H, 4 CH3ax), 1.40 (s, 12H, 4 CH3eq),
3.60 (d, J = 13 Hz, 8H, H-4ax, H-6ax), 4.11–4.15 [(m, 8H (H-4eq, H-6eq) &
4H (PhOCH2)], 4.33 (s, 8H, 4 CH2), 4.43 (t, J = 5 Hz, 4H, CH2OC=O),
6.81 (s, 4H, PhH); 13C{1H} NMR (125.7 MHz, CDCl3) ␦ 173.7 (4 C=O),
172.7 (2 C=O), 153.1, 115.9 (PhC), 98.2 (C-2), 66.4 (PhOCH2), 66.10,
66.06 (C-4, C-6), 65.4 (4 CH2), 63.8 (OCH2CH2OC=O), 46.9 (2 Cquat),
42.2 (4 Cquat), 25.3 (4 CH3eq). 22.2 (4 CH3ax), 18.6 (4 CH3), 17.8 (2 CH3).
HR EI MS: m/z calculated for C52H78NaO22: 1077.4877. Found
1077.4873.
General procedure for formation of dendritic esters
The acetonide-protected anhydride of 2,2-bis(hydroxymeth-
yl)propanoic acid, the hydroxyl-terminated dendrimer or core,
and N,N-dimethyl–4-aminopyridine (DMAP) were dissolved in a 3:1
mixture of CH2Cl2/pyridine (v/v) under a nitrogen atmosphere in
an oven-dried round-bottomed flask equipped with a magnetic
stir bar. The reaction mixture was stirred at room temperature for
4–6 h, and then diluted with water (3 mL) in pyridine (3 mL).
Stirring was continued overnight to quench the excess anhydride.
The mixture was diluted further using CH2Cl2 (60 mL), then
washed with NaHCO3 (1 mol/L, 3 × 15 mL), 10% Na2CO3 (3 × 15 mL),
brine (2 × 15 mL), water (15 mL), dried (MgSO4), filtered, and con-
centrated. The crude product was then purified using precipita-
tion out of hexanes/EtOAc or column chromatography to give the
desired product (>94% yield). The NaHCO3 layers were combined,
acidified (pH = 5–6), and the precipitated carboxylic acid by-
product was recovered.
1,4-Bis-(2-(2,2-bis(2,2-bis(hydroxymethyl)propanoyloxymethyl)
propanoyloxy)ethoxy)benzene (6)
Compound 5 (1.49 g, 1.41 mmol) was deprotected as described
above in the general procedure for the removal of isopropylidene
acetals to give the product as colourless crystals (1.24 g, 98% yield).
1H and 13C{1H} NMR data matched previously reported data.16
1,8-Bis-((2,2,5-trimethyl-1,3-dioxan-5-yl)propanoyloxy)octane (8)
1,8-Octanediol 7 (1.00 g, 6.84 mmol), dry pyridine (12 mL), CH2Cl2
(36 mL), DMAP (0.360 g, 2.95 mmol) and anhydride 2 (5.50 g,
16.6 mmol) were stirred at room temperature for 4 h under ni-
trogen. After work up and purification as described above, the
product was obtained as colourless oil (2.98 g, 95% yield): RF 0.49
(hexanes/EtOAc; 2: 1); 1H NMR (500.13 MHz, CDCl3) ␦ 0.92 (s, 6H, 2
CH3), 1.10–1.15 (m, 20H, 2 CH3ax, 2 CH3eq, 8 octyl H), 1.38 (quint, J =
6.5 Hz, 4H, octyl OCH2CH2), 3.36 (d, J = 11.5 Hz, 4H, H-4ax, H-6ax),
General procedure for the removal of isopropylidene
acetals
3.87 (t, J = 6.5 Hz, 4H, octyl OCH2), 3.90 (d, J = 11.5 Hz, 4H, H-4eq
,
H-6eq); 13C{1H} NMR (125.7 MHz, CDCl3) ␦ 173.5 (2 C=O), 97.3 (C-2),
65.4 (C-4, C-6), 64.1 (octyl OCH2), 41.2 (Cquat), 28.6 (octyl
OCH2CH2CH2CH2), 28.1 (octyl OCH2CH2), 25.2 (CH3eq), 23.9 (CH3ax),
22.5 (octyl OCH2CH2CH2), 18.2 (2 CH3). HR EI MS: m/z calculated for
C24H42NaO8: 481.2772. Found 481.2768.
An acetonide-protected dendrimer was dissolved in CH2Cl2
(5 mL) and the mixture was diluted using methanol (15 mL). A
teaspoon of DOWEX, H+ resin was added and the mixture was
stirred for 3 h at room temperature until TLC confirmed complete
removal of the protective groups. The resin was filtered off and
carefully washed with methanol. Methanol was removed under
vacuum to give hydroxyl-terminated products as colorless crystal-
line products (>96% yield).
1,8-Bis-(2,2-bis(hydroxymethyl)propanoyloxy)octane (9)
Compound 8 (2. 00 g, 4.36 mmol) was deprotected as described
above in the general procedure for the removal of isopropylidene
acetals to give the title compound (9) as a colourless crystalline
1,4-Bis-(2-((2,2,5-trimethyl-1,3-dioxan-5-yl)
methanoyloxy)ethoxy)benzene (3)
1
solid (1.58 g, 96% yield): RF 0.30 (EtOAc); mp 65–67 °C; H NMR
(500.13 MHz, CDCl3) ␦ 1.15 (s, 6H, 2 CH3), 1.36–1.43 (m, 8H, 8 octyl
H), 1.64 (quint, J = 6.5 Hz, octyl OCH2CH2), 3.65 (AB q, ⌬␯AB = 24.5 Hz,
JAB = 11 Hz, 8H, CH2OH), 4.10 (t, J = 6.5 Hz, 4H, octyl OCH2);
13C{1H} NMR (125.7 MHz, CDCl3) ␦ 176.5 (2 C=O), 65.7 (CH2OH), 65.6
(octyl OCH2), 51.3 (Cquat), 30.0 (octyl OCH2CH2CH2CH2), 29.4 (octyl
OCH2CH2), 26.8 (octyl OCH2CH2CH2), 17.3 (CH3). HR EI MS: m/z
calculated for C18H34NaO8: 401.2146. Found 401.2161.
1,4-Bis-(2-hydroxyethoxy)benzene 1 (0.750 g, 3.78 mmol), dry
pyridine (11 mL), CH2Cl2 (33 mL), DMAP (0.203 g, 1.66 mmol)
and 2,2,5-trimethyl-1,3-dioxane-5-carboxylic anhydride 2 (3.00 g,
9.08 mmol) were stirred at room temperature for 4 h under ni-
trogen. After work up and purification as described above, the prod-
uct was obtained as a colourless crystalline solid (1.85 g, 96% yield):
1
RF 0.50 (hexanes/EtOAc; 1:1); mp 75–77 °C; H NMR (500.13 MHz,
CDCl3) ␦ 1.17 (s, 6H, CH3), 1.35 (s, 6H, CH3ax), 1.40 (s, 6H, CH3eq), 3.62
(d, J = 12 Hz, 4H, H-4ax, H-6ax), 4.12 (t, J = 5 Hz, 4H, PhOCH2), 4.17 (d,
J = 11.5 Hz, 4H, H-4eq, H-6eq), 4.44 (t, J = 4.5 Hz, 4H, CH2OC=O), 6.82
Polymerization experiments
Polymerization reactions were performed at 120 °C in sealed
ampoules under an inert atmosphere. A molar ratio of catalyst/
Published by NRC Research Press

Keefe et al.
397
alcohol functionality of 1:1 and a variety of monomer/initiator
ratios were employed to obtain polymers of desirable molecular
weights. Sn(Oct)2 was used as a catalyst with rac-lactide and
L-lactide monomers and complex polyol initiators. The reaction
proceeded for 30 min and was followed by quenching with 10:1
(v/v) CHCl2/MeOH for 30 min. The polymer was precipitated by
dropwise addition to cold methanol followed by filtration and
drying in vacuo before performing analysis.
very grateful to Dr. Rabin Bissessur (UPEI) and Dr. Mark Obrovac
(Dal) for allowing us access to analytical instrumentation. We also
thank Ryan Fielden, Tom Tran, Christian Agatemor, and Gayan
Tennekone for technical assistance.
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Supplementary data
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