Lactide cyclopolymerization by an alumatrane-inspired catalyst

Article abstract of DOI:10.1021/ma201960p

A new catalyst for the ring-expansion polymerization of lactide to cyclic poly(lactic acid) was investigated. Catalyst 1(alumatrane-inspired catalyst, (N,N-bis(3,5-di-tert-butyl-2-benzyloxy)-2-(2-aminoethoxy)ethoxy)aluminum) was active for the polymerizat

Full text of DOI:10.1021/ma201960p

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Lactide Cyclopolymerization by an Alumatrane-Inspired Catalyst
Jonathan Weil,† Robert T. Mathers,‡ and Yutan D. Y. L. Getzler*,†
†Department of Chemistry, Kenyon College, Gambier, Ohio 43022, United States
‡Department of Chemistry, The Pennsylvania State University, New Kensington, Pennsylvania 15068, United States
S
* Supporting Information
INTRODUCTION
RESULTS AND DISCUSSION
Catalyst Synthesis. The synthesis of catalyst 1 is
straightforward and uses inexpensive materials (Scheme 1).
■
■
Control of molecular structure is an enduring motivation for
chemists. From total synthesis1 to self-assembly2 to crystal
growth,3 the pursuit continues unabated. Polymer synthesis, in
particular, has seen a revolution in control. It is now possible to
precisely predetermine chain length, extent of cross-linking,
comonomer incorporation, block length, stereochemistry and
topology.4 There has even been success in sequence control,5
previously achieved only in biological systems. The difficulties
inherent in the synthesis of pure macrocycle6 have limited their
availability, despite their compelling predicted properties. A
variety of strategies have been employed but only two avoid
linear material at all stages: catalyst-free ring equilibration and
ring-expansion polymerizations (REP).7 Our general catalyst
design has been influenced by a recent example of the latter
strategy wherein Grubbs used a ring-opening metathesis
polymerization (ROMP) catalyst modified with a permanently
tethered initiating group to polymerize cylcooctene yielding
high-molecular-weight rings free of any linear contaminants.8,9
Taking a cyclic catalyst and a cyclic monomer as our design
criteria, we focused on cyclic poly(lactic acid)(cPLA) as a
target. PLA architectures are interesting due to their
degradation profiles and because they can be renewably
sourced, and the cyclic architecture of cPLA in particular may
be advantageous in drug delivery.10 Whereas cyclic lactide
oligomer have been synthesized,11−13 we sought to produce
high-molecular-weight cPLA.10 N-Heterocyclic carbenes,14,15
organotin compounds16 and imidazoles17 have previously been
reported as effective catalysts for lactide REP to form cPLA.
Herein we report an alumatrane-inspired catalyst, (N,N-bis(3,5-
di-tert-butyl-2-benzyloxy)-2-(2-aminoethoxy)ethoxy)aluminum
[(tBu-SalAmEE)Al, 1], that is active for controlled cPLA
synthesis by lactide REP.
a
Scheme 1. Ligand and Catalyst Synthesis
a
Key: (a) C7H8, reflux. (b) 0.01 M 2, AlMe3, THF, reflux, N2, 5 days.
Ligand 2 was produced via Mannich condensation of the
relevant phenol and aminoalcohol in toluene under Dean−
Stark conditions. Although related ligand syntheses are
frequently driven by precipitation of the product,36,37
2
remained soluble, limiting yields. Despite this, 2 has been
isolated on >15 g scale. Metalation was more challenging as
initial attempts using known proceures29−33 yielded an
intractable and complex mixture of products that, remarkably,
included unreacted aluminum alkyls. Success required dilution
in THF and an extended (five day) reflux. The necessity of
both the relatively high dilution and lengthy reaction time were
verified separately. Characterization by 1H and 13C NMR
spectroscopies revealed a highly symmetric compound.
However, given the frequent dimerization of alumatranes
noted above, our representation of 1 as monomeric must be
taken as tentative. Detailed characterization of 1 is underway
and will be reported elsewhere.
Metallatranes, the trigonal bipyramidal complexes of tripodal
tetradentate ligands,18 have been widely used19−21 and continue
to be an area of active research.22−28 Of particular relevance to
this work are recent examples of monomeric alumatranes.29−31
Alumatranes are most commonly dimeric, and the alumatrane
dimers which have been examined for lactide polymerization
are inactive.32,33 However, a monomeric alumatrane-isopropa-
nol adduct capable of lactide polymerization in the melt has
been reported.32 Further inspiration was drawn from ligand
hemilability where changes in hapticity34 or denticity35 can
stabilize reactive catalytic intermediates or allow substrate
coordination.
Polymerization Activity and Polymer Characteriza-
tion. Catalyst 1 was active for the polymerization of lactide in
the melt and in solution and produced polymers with high
molecular weights and narrow polydispersities (Table 1). At
constant concentration of monomer and catalyst with
increasing reaction time, the conversion of monomer to
polymer steadily increased, consistent with a well-defined
catalyst (Table 1, entries 1−3). The system also clearly
Received: August 26, 2011
Revised: December 13, 2011
Published: January 9, 2012
© 2012 American Chemical Society
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dx.doi.org/10.1021/ma201960p | Macromolecules 2012, 45, 1118−1121

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a
Table 1. Solution and Melt Polymerizations of Lactide with Catalyst 1
d
MHS values
b
c
c
d
entry
solvent
[monomer]/ [catalyst]
time (h)
convn (%)
Mw (g/mol)
Mw/Mn
[η](mL/g)
α
K (mL/g)
1
2
3
4
5
6
7
8
9
toluene
toluene
toluene
toluene
toluene
toluene
melt
62
62
2
4
24
39
64
79
34
21
79
66
39
4080
6130
1.8
1.2
1.2
1.2
1.1
1.1
1.2
1.4
1.2
4.1
5.8
0.29
0.37
0.81
0.39
0.71
0.91
0.44
0.46
0.53
0.383
0.243
62
8
7380
8.7
0.006 74
0.290
52
12
12
12
2
9200
9.5
250
416
104
165
407
12 680
16 320
31 880
33 760
38 820
10.6
9.7
0.0135
0.002 47
0.239
21.8
22.9
26.1
melt
2
0.201
melt
2
0.109
a
Melt polymerizations were conducted under nitrogen at 130 °C using monomer and catalyst (3.5 mg). Solutions polymerizations were conducted
b
under nitrogen at 130 °C using monomer (106 mg), catalyst, and toluene (1.1 mL). Conversion was calculated from the 1H NMR spectrum of the
crude reaction mixture. Weight-average (Mw) molecular weights and molecular weight distributions (Mw/Mn) were calculated by gel-permeation
chromatography using light scattering in tetrahydrofuran (THF). Mark−Houwink−Sakarada (MHS) values and intrinsic viscosity ([η]) were
measured in THF at 35 °C using a gel-permeation chromatography system with light scattering and viscometer detectors.
c
d
displayed the expected time-dependent increases in both
molecular weight and intrinsic viscosity (Table 1, entries 1−
3). If reaction time was instead held constant, but catalyst
loading decreased, percent conversion displayed a concomitant
decline, consistent with fewer active polymerization sites (Table
1, entries 4−6). Fewer active sites should also produce material
with higher molecular weights, a trend which was observed in
the same data (Table 1, entries 4−6). Melt polymerizations by
catalyst 1 responded to decreasing catalyst loadings in an
analogous fashion (Table 1, entries 7−9), with decreased
conversion of monomer and increased molecular weights.
The polymerization activity of compound 1 was consistent
with a well-defined catalyst (Figure 1). Melt polymerizations
The proposed cyclic structure of 1 means that the polymer
formed from enchainment of lactide by 1 could also be cyclic.
We investigated this possibility by comparing the polymer to
authentic linear PLA, synthesized with a bis(2-ethylhexanoate)-
tin catalyst. When the absolute molecular weights and elution
volumes of linear PLA and the polymer produced by 1 were
compared, the latter eluted at higher volumes, consistent with
the smaller hydrodynamic volume of a cyclic topology
Figure 2. Molecular weight as a function of elution volume for linear
○
PLA (blue −) and the PLA produced by 1(green ).
(Figure 2). Further evidence for a cyclic topology was found
in overlaid Mark−Houwink-Sakurada plots of linear material
and the polymer formed by 1 (Figure 3). As expected, for a
given molecular weight, the linear material displayed a higher
intrinsic viscosity. Cyclic polymer topology is also supported by
MALDI−TOF MS data, where the dominant peaks are integer
multiples of the monomer (Supporting Information).
Figure 1. Conversion of lactide monomer in solution and melt
polymerizations as a function of catalyst loading and time. Conversion
was calculated from the 1H NMR spectrum of the crude reaction
□
mixture. Key: (blue ) 0.7 mmol of lactide, 1.1 mL of toluene, 12 h,
■
○
130 °C; (blue ) 6 μmol of 1, 2 h, 130 °C; (red ) 60:1 monomer:1,
●
5 μmol of 1, 0.55 mL of toluene, 130 °C; (red ) 190:1 monomer:1, 6
μmol of 1, 130 °C.
A plausible polymerization mechanism for the formation of
cPLA by 1 is shown in Scheme 2. Enchainment of lactide could
proceed through a coordination−insertion mechanism38 to
generate macrometallacycle 3, which would eventually undergo
an intramolecular chain transfer9 to liberate cPLA (4) and
regenerate free catalyst (1). We are interested in more closely
examining the kinetics of the system, particularly whether
molecular weight and molecular weight distribution can be
gave higher conversion with decreasing monomer-to-catalyst
ratio as did solution polymerizations. When concentrations
were instead held constant but reaction time was varied,
conversion increased with time as expected. Unsurprisingly, the
much higher concentrations of catalyst in the melt polymer-
izations resulted in much higher conversions at a given time
than the comparable solution polymerizations.
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ASSOCIATED CONTENT
■
S
* Supporting Information
Detailed experimental procedures and characterization of new
compounds including MALDI−TOF and NMR spectra (two
files). This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: getzlery@kenyon.edu.
ACKNOWLEDGMENTS
■
This work was generously supported by Kenyon College
Summer Science Scholars Program (J.W.), Kenyon College
Startup Funds, the American Chemical Society’s Petroleum
Research Fund (42880-GB 7)(YDYLG). R.T.M. thanks the
donors of the American Chemical Society’s Petroleum Research
Fund and the Alcoa Foundation for support.
Figure 3. Mark−Houwink−Sakurada plot of linear PLA (blue) and
PLA produced by 1 (green), each overlaid with their respective linear
regressions.
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Scheme 2. Proposed Mechanism for the Ring-Expansion
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We presented a new catalyst for the ring-expansion polymer-
ization of lactide to cyclic poly(lactic acid). The pseudoaluma-
trane complex contains a putative initiating group tethered to a
permanently bound ligand, analogous to Grubbs’ catalyst for
ring-expansion polymerization of cyclooctene. Our catalyst is
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