Aluminum salen and salan complexes in the ring-opening polymerization of cyclic esters: Controlled immortal and copolymerization of rac-β- butyrolactone and rac-lactide

Article abstract of DOI:10.1002/pola.26476

Aluminum-based salen and salan complexes mediate the ring-opening polymerization (ROP) of rac-β-butyrolactone (β-BL), rac-lactide, and ε-caprolactone. Al-salen and Al-salan complexes exhibit excellent control over the ROP of rac-β-butyrolactone, yielding atactic poly(3- hydroxybutyrate) (PHB) with narrow PDIs of <1.15 for Al-salen and <1.05 for Al-salan. Kinetic studies reveal pseudo-first-order polymerization kinetics and a linear relationship between molecular weight and percent conversion. These complexes also mediate the immortal ROP of rac-β-BL and rac-lactide, through the addition of excess benzyl alcohol of up to 50 mol eq., with excellent control observed. A novel methyl/adamantyl-substituted Al-salen system further improves control over the ROP of rac-lactide and rac-β-BL, yielding atactic PHB and highly isotactic poly(lactic acid) (P_m = 0.88). Control over the copolymerization of rac-lactide and rac-β-BL was also achieved, yielding poly(lactic acid)-co-poly(3-hydroxybutyrate) with narrow PDIs of <1.10. ¹H NMR spectra of the copolymers indicate a strong bias for the insertion of rac-lactide over rac-β-BL. 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013. Copyright

Full text of DOI:10.1002/pola.26476

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Aluminum Salen and Salan Complexes in the Ring-Opening
Polymerization of Cyclic Esters: Controlled Immortal and
Copolymerization of rac-b-Butyrolactone and rac-Lactide
Edward D. Cross,1 Laura E. N. Allan,2 Andreas Decken,3 Michael P. Shaver1,2
1Department of Chemistry, University of Prince Edward Island, 550 University Ave., Charlottetown, Prince Edward Island,
Canada C1A 4P3
2School of Chemistry, University of Edinburgh, King’s Buildings, West Mains Road, Edinburgh, EH9 3JJ,
United Kingdom
3Department of Chemistry, University of New Brunswick, P.O. Box 6600, Fredericton, New Brunswick, Canada E3B 5A3
Correspondence to: M. P. Shaver (E-mail: michael.shaver@ed.ac.uk)
Received 2 November 2012; accepted 11 November 2012; published online 5 December 2012
DOI: 10.1002/pola.26476
ABSTRACT: Aluminum-based salen and salan complexes mediate
the ring-opening polymerization (ROP) of rac-b-butyrolactone (b-
BL), rac-lactide, and e-caprolactone. Al-salen and Al-salan com-
plexes exhibit excellent control over the ROP of rac-b-butyrolac-
tone, yielding atactic poly(3-hydroxybutyrate) (PHB) with narrow
PDIs of <1.15 for Al-salen and <1.05 for Al-salan. Kinetic studies
reveal pseudo-first-order polymerization kinetics and a linear rela-
tionship between molecular weight and percent conversion. These
complexes also mediate the immortal ROP of rac-b-BL and rac-lac-
tide, through the addition of excess benzyl alcohol of up to 50 mol
eq., with excellent control observed. A novel methyl/adamantyl-
substituted Al-salen system further improves control over the ROP
of rac-lactide and rac-b-BL, yielding atactic PHB and highly isotac-
tic poly(lactic acid) (Pm ¼ 0.88). Control over the copolymerization
of rac-lactide and rac-b-BL was also achieved, yielding poly(lactic
acid)-co-poly(3-hydroxybutyrate) with narrow PDIs of <1.10. 1H
NMR spectra of the copolymers indicate a strong bias for the
C
V
insertion of rac-lactide over rac-b-BL. 2012 Wiley Periodicals, Inc.
J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 1137–1146
KEYWORDS: biodegradable; copolymerization; ring-opening poly-
merization; rac-b-butyrolactone; rac-lactide
lective ROP of rac-b-BL,12 and some studies on group 4,13
Sn,14–18 and Cr19 systems have been reported, aluminum
complexes that can polymerize this monomer in a controlled
and stereoregular manner have remained relatively
unexplored.20
INTRODUCTION Interest in the development of biodegrad-
able polyesters, in particular poly(lactic acid) (PLA), poly
(glycolic acid), poly(e-caprolactone) (PCL), and their copoly-
mers, has continued to increase,1–4 finding application in
nanotechnology, thermoplastic, commodity, and biomedical
industries.5–8 Although these polymers remain at the fore-
front of research efforts in this field, other classes of biode-
gradable polyesters such as the poly(hydroxyalkanoate)s
have begun to attract greater focus in the past decade.9
Poly(3-hydroxybutyrate) (PHB) has been of particular inter-
est as it is produced with high isotactic stereoregularity by
bacteria, resulting in semicrystalline PHB with a Tg and Tm
of approximately 5 ꢀC and 180 ꢀC, respectively, giving it
properties similar to that of isotactic polypropylene.10 Alter-
natively, ring-opening polymerization (ROP) of b-butyrolac-
tone (b-BL) using metal-based initiators has provided an
additional route to this biodegradable polyester,11 allowing
access to PHB with predictable molecular weights, narrow
polydispersity indecies (PDIs), and different stereoregularity
to the isotactic bacterial PHB. Although rare-earth complexes
have been shown to be proficient at mediating the stereose-
Although homopolymerizations of these monomers remain
important, access to novel biodegradable materials can be
achieved by the copolymerization of two or more judiciously
chosen monomers, targeting a material with unique proper-
ties. In particular, complexes that effectively mediate the ROP
of both rac-b-BL and rac-lactide, and are effective in the
copolymerization of these monomers, remain scarce (Scheme
1). It has been reported that tin alkoxides copolymerize (R)-
b-BL and L-lactide, producing poly((R)-3-hydroxybutyrate)-
co-poly (L-lactic acid) where the incidence of PHB and PLA
in the copolymer correlated well with the initial monomer
feed ratio.21 However, these copolymers possessed substan-
tially broadened PDIs of >1.7. The copolymerization of rac-
b-BL and L-lactide mediated by dibutylmagnesium produced
similar results, with good correlation between the ratio of
monomers in the feed and the composition of the resulting
Additional Supporting Information may be found in the online version of this article.
C
V
2012 Wiley Periodicals, Inc.
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FIGURE 1 Al-salen complex 1 and Al-salan complex 2, previ-
ously reported as efficient and stereoselective mediators for
the ROP of rac-lactide.
ratories, were dried over calcium hydride at reflux overnight
prior to vacuum transfer, and were degassed by three freeze–
pump–thaw cycles prior to use. rac-b-Butyrolactone (ꢁ98%)
was dried over calcium hydride overnight at ambient tempera-
ture, distilled under vacuum, and degassed by three freeze–
pump–thaw cycles prior to use. PURASORB DL-lactide was
obtained from PURAC Biochem by Gorinchem and sublimed
three times under vacuum prior to use. e-Caprolactone was
dried over calcium hydride and distilled under inert atmos-
phere prior to use. Complexes 124,31 and 225 as well as 3-ada-
mantyl-2-hydroxy-4-methylbenzaldehyde15,16 were prepared
according to literature procedures.
SCHEME 1 Biodegradable polyester materials.
copolymer and PDIs of >1.6.22 Hafnium amine-tris(pheno-
late) complexes also successfully copolymerized rac-b-BL and
rac-lactide, again with broad PDIs of >1.6. The authors also
noted that the rate of insertion of rac-b-BL into the copolymer
was significantly slower than that observed for rac-lactide
when the polymerization was monitored by 1H NMR spectros-
copy,13 producing a copolymer composed of two distinct
blocks rather than the expected random or gradient copoly-
mer. Narrow PDIs (<1.1) were obtained only when using se-
quential addition of rac-b-BL followed by rac-lactide. In terms
of group 3 complexes, it was demonstrated that an aluminum
half-salen complex that hadꢀsimilar observed rates in rac-b-BL
and rac-lactide ROP at 90 C in toluene was unsuccessful at
mediating the copolymerization. There was no incorporation
of rac-b-BL during the copolymerization with only PLA
formed, even after extended polymerization times.23
Toluene and pentane were obtained from an Innovative
Technologies glovebox equipped with an inline Solvent Puri-
fication System, consisting of columns of alumina and copper
catalyst. The solvents were degassed by three freeze–pump–
thaw cycles prior to use. All air-sensitive manipulations were
performed in an MBraun LABmaster sp glovebox or on a
dual manifold vacuum line using standard Schlenk techni-
ques. 1H (300 MHz) and 13C{1H} NMR (75 MHz) spectra
were collected on a Bruker Avance 300 spectrometer. Gel
permeation chromatography (GPC) was performed on a Poly-
mer Laboratories PL-GPC 50 Plus integrated GPC system
with two 300 ꢂ 7.8 mm2 Jordi Gel divinylbenzene mixed
bed columns, using HPLC grade tetrahydrofuran (THF) at a
flow rate of 1 mL minꢃ1 at 50 ꢀC, using a refractive index
detector and poly (styrene) standards for molecular weight
determinations, with conversion factors of 0.58 and 0.60 for
PHB and PLA, respectively.32 Copolymers of rac-b-BL and
rac-lactide were analyzed using a Wyatt Technology mini-
For this study, we used aluminum-based salen (salen ¼ N,N0-
bis(salicylaldimine)-1,2-ethylenediamine) and salan (salan ¼
N,N0-bis(o-hydroxybenzyl)-1,2-diaminoethane) complexes
1
and 2 (Fig. 1),24,25 known to produce well-controlled PLA
with narrow PDIs,24,26–30 and explored their ability to medi-
ate the ROP of rac-b-BL. We then used these tetradentate
salen and salan aluminum complexes in the copolymerization
of rac-b-BL and rac-lactide, comparing their activity to previ-
ously reported systems and targeting poly(lactic acid)-co-
poly(3-hydroxybutyrate) materials of controlled molecular
weights and narrow polydispersities. We also wished to
investigate whether these aluminum systems display a pref-
erence for the insertion of rac-lactide over rac-b-BL, in the
hopes of generating gradient materials.
DAWNTM TREOS multiple angle light scattering (MALS) de-
R
V
tector operating at 658 nm and using dn/dc values for PLA
and PHB of 0.05017 and 0.065,18 respectively. Differential
scanning calorimetry (DSC) analyses were completed on a
TA Instruments DSC Q100 in hermetically sealed aluminum
pans. A nitrogen flow rate of 50 mL minꢃ1 and heating pa-
EXPERIMENTAL
ꢃ1
ꢀ
rameters of 5 C min for heating and cooling were used.
Materials
All chemicals and solvents were obtained from Sigma-Aldrich
unless otherwise stated. 4-Methylphenol, 1-adamantanol
(99%), tin(IV)chloride (97%), paraformaldehyde powder
(95%), 1,2-diaminoethane (ꢁ99%), N,N0-dibenzylethylenedi-
amine (97%), and trimethylaluminum (2.0 M solution in hep-
tane) were used as received. Triethylamine (ꢁ99%) was dried
over calcium hydride at ambient temperature overnight prior
to vacuum transfer and was degassed by three freeze–pump–
thaw cycles prior to use. Benzene-d6 (D, 99.5%) and toluene-
d8 (D, 99.94%) were purchased from Cambridge Isotope Labo-
Synthesis and Characterization of 3
3-Adamantyl-2-hydroxy-4-methylbenzaldehyde (0.87 g, 3.2
mmol) was dissolved in absolute ethanol (10 mL). To this so-
lution, 1,2-diaminoethane (0.10 g, 1.6 mmol) was added, fol-
lowed by several drops of formic acid before the mixture
was heated to reflux, with a yellow precipitate observed af-
ter 30 min. After 4 h, heating was ceased and the mixture
was allowed to cool to room temperature. The yellow precip-
itate was filtered and washed with cold absolute ethanol.
Yield: 0.66 g (73%).
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1H NMR (300 MHz, CDCl3, d, ppm): 13.67 (s, AOH, 2H), 8.34
(s, ArCH¼¼N, 2H), 7.06 (s, ArH, 2H), 6.88 (s, ArH, 2H), 3.91
(s, NACH2CH2AN, 4H), 2.17 (m, AdH and ArCH3, 30H), 1.80
(bs, AdH, 15H) ppm. 13C{1H} NMR (75 MHz, CDCl3, d, ppm):
167.8, 158.8, 137.7, 131.0, 129.9, 127.1, 118.7, 59.9, 40.7,
37.6, 37.4, 37.3, 29.5, 21.1 ppm. Anal. For C38H48N2O2 Calcd.:
C, 80.81; H, 8.57; N, 4.96. Found: C, 81.12; H, 8.40; N, 5.10.
ArCH2N, 6H), 2.50 (m, AdH, 14H), 2.34 (s, ArCH3, 6H),
13C{1H} NMR (75 MHz, C6D6, d, ppm): 157.5, 140.0, 132.8,
129.7, 129.2, 129.1, 120.9, 41.2, 38.1, 37.9, 30.4, 21.5 ppm.
Anal. For C53H65AlN2O2 Calcd.: C, 80.67; H, 8.30; N, 3.55.
Found: C, 80.52; H, 8.13; N, 3.48.
General Conditions for the Living ROP of Cyclic Esters
An example of a typical living polymerization procedure is as
follows: in a nitrogen filled glovebox, 2 (0.0366 g, 0.055
mmol) and benzyl alcohol (6.0 lL, 0.055 mmol) were dis-
solved in toluene (3 mL) and allowed to stir at ambient tem-
perature for 5 min. This was followed by the addition of rac-b-
BL (0.500 g, 5.46 mmol). The ampoule was sealed, removed
Synthesis and Characterization of 4
2-Adamantyl-4-methylphenol (2.25 g, 9.3 mmol) was dis-
solved in absolute ethanol (10 mL). To this solution, N,N0-
dibenzyl-1,2-diaminoethane (1.12 g, 4.6 mmol) was added,
followed by paraformaldehyde (0.96 g, 9.3 mmol) before the
mixture was heated to reflux. After 18 h, heating was ceased
and the mixture was allowed to cool to room temperature. A
white precipitate formed and was filtered and washed with
cold absolute ethanol. Yield: 2.45 g (35%).
ꢀ
from the glovebox, and heated at 70 C for 6 h. The ampoule
was then cooled to room temperature and methanol (0.5 mL)
was added, and the solution was left to stir for 30 min at ambi-
ent temperature. The solution was then precipitated into cold
methanol (100 mL) before the white precipitate was filtered
and dried under vacuum to constant weight.
1H NMR (300 MHz, CDCl3, d, ppm): 10.36 (bs, AOH, 2H),
7.31 (m, ArH, 10H), 6.92 (s, ArH, 2H), 6.59 (s, ArH, 2H), 3.61
(s, ArCH2, 4H), 3.50 (s, PhCH2N, 4H), 2.65 (s, ArCH3, 6H)
ppm. 13C{1H} NMR (75 MHz, CDCl3, d, ppm): d 154.4, 136.9,
129.8, 128.7, 127.7, 127.5, 126.9, 122.1, 59.0, 58.3, 49.8,
41.5, 40.6, 37.4, 37.3, 36.9, 29.4, 29.3, 21.0 ppm. Anal. For
General Conditions for the Immortal ROP of Cyclic Esters
An example of a typical immortal polymerization procedure
is as follows: in a nitrogen filled glovebox, 2 (0.0084 g,
0.014 mmol) and benzyl alcohol (7.5 lL, 0.069 mmol) were
dissolved in toluene (3 mL) and allowed to stir for 5 min.
This was followed by the addition of rac-lactide (1.00 g, 6.94
mmol). The ampoule was sealed, removed from the glovebox,
C52H64N2O2 Calcd.: C, 83.38; H, 8.61; N, 3.74. Found: C,
83.18; H, 8.44; N, 4.02.
Synthesis and Characterization of 5
ꢀ
and heated at 70 C for 24 h. The ampoule was then cooled
In a nitrogen filled glovebox, 3 (0.90 g, 1.6 mmol) was dis-
solved in toluene (15 mL) and added to an oven-dried am-
poule. With vigorous stirring, a 2.0 M solution of trimethyla-
luminum in heptane (0.55 g, 1.6 mmol) was added dropwise.
Effervescence was observed, and the ampoule was sealed,
removed from the glovebox, and heated to 110 ꢀC. After 24
h, a yellow precipitate formed and the ampoule was allowed
to cool to room temperature. The precipitate was filtered
and washed with pentane. Yield: 0.41 g (43%).
to room temperature, a crude sample was removed for 1H
NMR spectroscopic analysis and 0.5 mL of a solution com-
prising 1% conc. HCl in methanol (v/v) was added. The solu-
tion was then precipitated into cold methanol (100 mL)
before the white precipitate was filtered and dried under
vacuum to constant weight.
General Conditions for the Copolymerization of rac-b-BL
and rac-Lactide
1H NMR (300 MHz, C6D6, d, ppm): 7.33 (s, ArCH¼¼N, 2H),
7.32 (s, ArH, 2H), 6.60 (d, ArH, 2H, J ¼ 1.8 Hz), 2.93 (dd,
NACH2CH2AN, 2H, J ¼ 6.3, 12.3 Hz), 2.51 (br, AdH and
NACH2CH2AN, 14 H), 2.28 (s, ArCH3, 6H) 2.18 (br, AdH, 6H),
1.87 (bm, AdH, 14H) ꢃ0.41 (s, AlCH3, 3H). 13C{1H} NMR (75
MHz, C6D6, d, ppm): 168.2, 165.4, 142.2, 138.2, 135.0, 131.3,
129.7, 126.0, 124.5, 120.1, 54.0, 41.5, 38.3, 38.0, 30.2, 21.7,
21.1 ppm. Anal. For C39H49AlN2O2 Calcd.: C, 77.45; H, 8.17;
N, 4.63. Found: C, 77.27; H, 8.03; N, 4.39.
An example of a typical copolymerization procedure is as fol-
lows: in a nitrogen filled glovebox, rac-lactide (0.500 g, 3.46
mmol), rac-b-BL (0.299 g, 3.46 mmol), 2 (0.0219 g, 0.035
mmol), and benzyl alcohol (3.6 lL, 0.035 mmol) were added
to an ampoule. The ampoule was sealed, removed from the
glovebox, and heated at 120 ꢀC for 6 h. The ampoule was then
cooled to room temperature and the residue was dissolved in
a 10:1 (v/v) mixture of CH2Cl2:MeOH. After stirring for 30 min
1
at ambient temperature, a sample was removed for H NMR
spectroscopic analysis. The solution was then precipitated into
cold methanol (100 mL) before the precipitate was filtered
and dried under vacuum to constant weight.
Synthesis and Characterization of 6
In a nitrogen filled glovebox, 4 (0.82 g, 1.1 mmol) was dis-
solved in toluene (15 mL) and added to an oven-dried am-
poule. With vigorous stirring, a 2.0 M solution of trimethyla-
luminum in heptane (0.36 g, 1.1 mmol) was added dropwise.
Effervescence was observed, and the ampoule was sealed,
removed from the glovebox, and heated to 110 ꢀC. After 24
h, a white precipitate formed and the ampoule was allowed
to cool to room temperature. The precipitate was filtered
and washed with pentane. Yield: 0.56 g (66%).
RESULTS AND DISCUSSION
Al-salen complex 1 and Al-salan complex 2 (Fig. 1) were
chosen as representative complexes to be used in this study
due to their facile synthesis and ability to mediate the ROP
of rac-lactide with both excellent control over molecular
weights and PDIs and high polymer tacticity.24,25 We
extended this study by targeting novel Al-salen and Al-salan
complexes with methyl and adamantyl substitutions on the
phenolate rings (5 and 6, Scheme 2), inspired by other
1H NMR (300 MHz, C6D6, d, ppm): 7.23 (s, ArH, 2H), 7.05
(m, ArH, 10H), 6.49 (s, ArH, 2H), 4.10–3.52 (br, ArCH2 and
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SCHEME 2 Synthesis of novel adamantyl-substituted complexes 5 and 6 via ligands 3 and 4.
ortho-substituted adamantyl phenoxide ligands,33,34 antici-
pating that 5 would give us improved tacticity control. Treat-
ment of 3 and 4 with trimethylaluminum in toluene at 110
ꢀC for 24 h allowed access to pure 5 and 6 in moderate iso-
lated yields due to the high solubility of the complexes in a
variety of solvents. Single crystals of 5 were grown by slow
evaporation of a concentrated solution of 5 in toluene
(Fig. 2). The Al center exists in a distorted square pyramidal
coordination environment, evident by the O(1)AAl(1)AO(2),
N(1)AAlAN(2), O(1)AAl(1)AC(1), and N(1)AAl(1)AC(1)
angles of 94.54(4), 76.50(5), 117.58(6), and 93.04(6),
respectively. The bond lengths and angles for 5 are compara-
ble to other sterically hindered Al-salen systems.31
an ‘‘immortal’’ mechanism through the addition of excess alco-
hol to serve as a chain-transfer agent.35–38 This immortal
mechanism was first proposed by Inoue and coworkers using
Al-porphyrin systems for epoxides and b-lactones.39 Although
several different systems have been shown to operate quite
efficiently via this immortal mechanism,40 Al-salen and salan
systems have not been fully studied with regard to the upper
limits of monomer and catalyst loadings, maintaining control
over the polymerization. To this end, Al-salen and salan sys-
tems 1, 2, and 5 were examined in depth as mediators of the
immortal ROP of rac-lactide (Table 1, Entries 5–16).
In the immortal ROP of rac-lactide mediated by 1, 2, and 5
using benzyl alcohol as the chain-transfer agent, experimen-
tal molecular weights agreed well with theoretical molecular
The ability of complexes 5 and 6 to mediate the living ROP
of rac-lactide was examined at 70 ꢀC in toluene to allow
comparison with similar systems. These ligand frameworks
represent a modest change in steric bulk and electronics due
to the decreased bite-angle of the ligand when comparing
salen complexes 131 and 5, but a significant change in both
sterics and electronics when comparing salan complexes 225
and 6. It has already been shown that bulky dialkyl-substi-
tuted Al-salan complexes exhibit poor activity in the ROP of
rac-lactide,25 and thus a similar trend was expected. This
was confirmed, with only trace amounts of PLA oligomers
isolated after 24 h at 70 ꢀC in toluene using 6 (Table 1,
Entry 4). In contrast, 5 was effective in mediating the living
ROP of rac-lactide (Table 1, Entries 1–3). Experimental mo-
lecular weights correlated well with the theoretical values
and narrow PDIs were obtained. 1H{1H} NMR spectra of the
resultant PLA showed 88% isotactic enchainment of lactide
monomer (Supporting Information Fig. S1), the highest iso-
specificity reported for a salen complex with an ethylene
bridge. Furthermore, increasing the [M]/[Al] ratio produced
PLA of correspondingly higher molecular weight (Supporting
Information Fig. S2). Previous reports have shown that Al-
salen complexes may also mediate the ROP of rac-lactide by
FIGURE 2 Molecular structure of
5 with thermal ellipsoids
drawn at 50% probability and hydrogen atoms omitted for
clarity. Selected bond lengths (A) and angles (ꢀ) include:
˚
Al(1)AO(1), 1.8215(9); Al(1)AO(2), 1.8321(9); Al(1)AC(1),
1.9728(15); Al(1)AN(1), 2.0351(11); Al(1)AN(2), 2.0391(11);
O(1)AAl(1)AO(2),
94.54(4);
O(1)AAl(1)AC(1),
117.58(6);
O(1)AAl(1)AN(1), 87.92(4); O(1)AAl(1)AN(2), 127.78(4).
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TABLE 1 Living ROP of rac-Lactide Using 5 and 6 and Immortal ROP of rac-Lactide Using 1, 2, and 5a
% Conv.b
Mn,th
Mn
PDId
Pm/Pre
c
d
Entry
Complex
[M]:[Al]:[BnOH]
Time (h)
1
5
5
5
6
1
1
1
1
2
2
2
2
5
5
5
5
100:1:1
12
18
24
24
24
24
24
24
24
24
24
24
24
24
24
24
49
78
56
<5
87
99
94
85
43
31
39
56
84
86
95
39
c
7,000
28,200
40,400
–
6,100
26,200
33,600
–
1.07
1.04
1.04
–
0.88 (m)
2
250:1:1
0.89 (m)
3
500:1:1
0.88 (m)
4
100:1:1
–
5
500:1:2
31,200
14,400
6,900
12,400
15,600
4,600
2,900
8,100
30,400
12,400
6,900
5,700
28,300
15,600
7,400
17,900
11,400
3,800
2,900
7,300
20,100
7,300
5,000
4,800
1.14
1.20
1.16
1.06
1.03
1.04
1.05
1.03
1.09
1.02
1.07
1.07
–
6
500:1:5
–
7
500:1:10
1,000:1:10
500:1:2
–
8
0.86 (m)
9
–
10
11
12
13
14
15
16
a
500:1:5
–
500:1:10
1,000:1:10
500:1:2
–
0.76 (r)
–
500:1:5
–
500:1:10
1,000:1:10
–
0.88 (m)
Polymerizations were conducted in 3 mL of toluene with 0.058 mmol
of Al complex at 70 ꢀC, using benzyl alcohol to generate the active
alkoxide and function as the chain-transfer agent where applicable.
Calculated by ([M]/[Al]) ꢂ MW (monomer) ꢂ (% conv.) þ MW (end group).
Obtained from SEC (GPC).
d
e
Probability of a meso or racemic linkage determined by examination
b
Determined by gravimetric analysis after drying under vacuum to con-
of the methine region of 1H{1H} NMR spectra.
stant weight.
weights when the ratio of benzyl alcohol was increased from
2 to 10 with respect to a constant [M]/[Al] ratio of 500.
Moderate conversion was observed using 2, whereas 1 and
5 showed much higher conversion after 24 h at 70 ꢀC in 3
mL of toluene. No significant loss of control was observed
when increasing the amount of chain-transfer agent, as
shown by the lack of broadening in PDIs. Increasing the ini-
tial monomer feed to 1000 relative to a 10:1 ratio of benzyl
alcohol:complex to test the behavior of the system at higher
loadings resulted in well-controlled polymerizations, similar
to those reported for a related aluminum-based salen com-
plex under these conditions.38 A slight decrease in tacticity
was observed for Al-salen complexes 124 and 5 under
immortal conditions, but a more significant decrease was
observed for Al-salan complex 2, where a Pr of 0.94 was
reported under living conditions25 but a Pr value of only
0.76 was obtained under immortal conditions. It was
observed that at monomer to catalyst ratios of greater than
1000:1, no productive polymerization occurred. This was
most likely due to the high concentration of lactide, which
resulted in coordination of the monomer to the aluminum
center, effectively rendering the complex inactive. However,
up to these loadings, benzyl alcohol serves as an excellent
chain-transfer agent for the Al-salen and Al-salan systems
and supports previous reports35–38 that these systems serve
as effective catalysts in the immortal ROP of rac-lactide.
times. Contrasting these reports, we have found that Al-salen
and salan complexes 1, 2, and 5 are excellent catalysts for
the ROP of rac-b-BL under a range of conditions (Table 2).
The control over molecular weight and PDIs for rac-b-BL
polymerizations mediated by 1, 2, and 5 was significantly
improved over those using related aluminum ‘‘half’’ salen
complexes.23 Both bulk and solution polymerizations at 70
ꢀC mediated by 1 and 2 resulted in excellent control over
molecular weights and PDIs, with slightly narrower PDIs
observed for the solution polymerizations, even when a coor-
dinating solvent was used (Table 2, Entries 1 and 2 for 1
and Entries 9–11 for 2). Although polymerizations mediated
ꢀ
by 1 at 120 C exhibited faster rates and a significant broad-
ening in PDI compared to polymerizations at 70 ꢀC, the use
of higher temperatures when using 2 did not result in a loss
of control (Table 2, Entries 2 and 3 for 1; Entries 10 and 12
for 2), illustrating the versatile nature of the Al-salan system.
When 2 was used for the ROP of rac-b-BL, narrow PDIs of
<1.05 were observed, at temperatures ranging from 25 to
120 ꢀC (Table 2, Entries 6–12), and an increase in [M]/[Al]
gave PHB of the corresponding increased molecular weight
(Table 2, Entries 10, 13, and 14). Narrow PDIs of <1.15
were observed for rac-b-BL polymerizations mediated by Al-
salen catalysts 1 and 5, but while calculated molecular
weights correlated well to theoretical molecular weights for
1, increasing the [M]/[Al] for 5 did not produce PHB of the
corresponding increased molecular weight (Table 2, Entries
15 and 16, cf. Entries 2, 4, and 5 for 1).
Although Al-based salan complexes have not previously been
studied in the ROP of rac-b-BL, bis-Al-salen complexes have
been used,41–43 although only low molecular weight oligom-
ers were produced even after prolonged polymerization
Upon investigation of the methylene and the carbonyl region
in 13C{1H} NMR spectra of the isolated PHB, no stereocontrol
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TABLE 2 Polymerization of rac-b-BL Using Al-salen and Al-salan Complexes 1, 2, and 5a,b
% conv.c
Mn,th
Mn
PDIe
d
e
Entry
Complex
[M]/[Al]
Solvent
Temp. (ꢀC)
Time (h)
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
5
5
100
100
100
250
500
100
100
100
100
100
100
100
250
500
100
250
Neat
70
70
120
70
70
25
25
25
70
70
70
120
70
70
70
70
3
58
58
82
94
82
73
58
75
72
99
89
94
81
90
28
41
5,100
5,100
7,100
20,300
35,400
6,400
4,800
6,600
6,300
8,600
7,800
8,300
17,500
38,800
3,600
8,800
5,900
5,100
7,400
16,600
25,800
6,200
6,400
6,400
6,100
8,600
8,200
7,400
19,600
35,700
2,400
4,900
1.08
1.06
1.35
1.14
1.09
1.03
1.03
1.03
1.04
1.03
1.03
1.05
1.03
1.04
1.05
1.04
2
Toluene
Toluene
Toluene
Toluene
Neat
6
3
6
4
18
36
24
48
48
3
5
6
7
Toluene
THF
8
9
Neat
10
11
12
13
14
15
16
a
Toluene
THF
6
6
Toluene
Toluene
Toluene
Toluene
Toluene
2
10
20
12
18
c
Polymerizations were conducted with 0.058 mmol of [Al] in 3 mL of
solvent, where applicable, using 1 eq. benzyl alcohol to generate the
active alkoxide.
Determined by gravimetric analysis after drying under vacuum to con-
stant weight.
d
Calculated by ([M]/[Al]) ꢂ MW (rac-b-BL) ꢂ (% conv.) þ MW (end
b
All PHB isolated possessed an atactic microstructure, determined by
group).
13C{1H} NMR spectroscopy.
Obtained from SEC (GPC).
e
was observed regardless of solvent or temperature, confirm-
ing that catalysts 1, 2, and 5 produce solely atactic PHB.
Kinetic experiments performed at 70 ꢀC in benzene-d6
confirmed that 1, 2, and 5 mediate living ring-opening poly-
merization of rac-b-BL. Pseudo-first-order reaction kinetics
with respect to monomer were observed in plots of ln([M]0/
[M]t) versus time, although a slight delay of approximately
15 min was introduced due to the time required to heat the
polymerization to 70 ꢀC prior to the collection of spectra.
Plots of Mn versus percent conversion revealed a linear rela-
tionship with excellent agreement between experimental and
theoretical molecular weight values (Fig. 3, Supporting Infor-
mation Figs. S3 and S4). Signals in the 1H NMR spectra
corresponding to a benzyl ester end group were observed at
d 5.2 ppm for polymers produced by each of the complexes,
with no evidence of carboxyl or crotonate end groups. These
results suggest that the ROP of rac-b-BL by 1, 2, and 5 pro-
ceeds via a standard coordination-insertion mechanism, with
2 exerting the best control over molecular weights and PDIs
by an Al-based complex for the living ROP of rac-b-BL
reported to date.
Following our study using 1, 2, and 5 for the living ROP of
rac-b-BL, we sought to investigate the versatility of these
complexes by introducing an excess of benzyl alcohol and
entering an immortal ROP regime. Experimental molecular
weights agreed well with theoretical molecular weights
when the ratio of catalyst to benzyl alcohol was increased
from 2 to 50 with respect to a constant [M]/[Al] ratio of 500
FIGURE 3 Plot of ln([M]0/[M]t) versus time (min) (left) and Mn versus percent conversion (right) (solid line ¼ Mn,th) for ROP of rac-
b-BL by 2 at 70 ꢀC in benzene-d6 with [M]/[Al] ¼ 100.
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TABLE 3 Immortal Ring-Opening Polymerization of rac-b-BL by
tions and copolymerizations of e-caprolactone, Al-salen 1
and Al-salan 2 have not been studied. When the ROP of e-
caprolactone was attempted using complexes 1, 2, and 5,
they were unable to provide a significant degree of control
over the molecular weight of the PCL and exhibited substan-
tially broadened PDIs (Supporting Information Table S1).
Manipulation of the monomer concentration, temperature, or
solvent did not produce any noteworthy improvement in
control over the molecular weights or PDIs. It was also
observed that the polymerizations progressed at a surpris-
ingly slow rate, given the higher reactivity of the e-caprolac-
tone monomer, with solution polymerizations only reaching
about 70% conversion after 6 h in tolueneꢀ, whereas neat
polymerizations reached 75% after 7 h at 70 C.
1, 2, and 5a
Entry Complex [M]:[Al]:[BnOH] % conv.b Mn,th Mn
PDId
c
d
1
1
1
1
1
1
1
2
2
2
2
2
2
2
5
500:1:2
40
70
57
75
50
61
92
85
82
84
98
98
99
<5
8,700 8,100 1.07
6,000 4,540 1.06
2,500 2,100 1.08
1,400 1,100 1.07
2
500:1:5
3
500:1:10
500:1:25
500:1:35
500:1:50
500:1:2
4
5
700
600
800
900
1.09
1.08
6
7
19,800 16,300 1.05
7,400 7,500 1.03
3,600 3,200 1.11
1,500 1,600 1.08
1,300 1,200 1.05
8
500:1:5
9
500:1:10
500:1:25
500:1:35
500:1:50
1,000:1:50
500:1:2
10
11
12
13
14
a
With optimized protocols determined for the living and
immortal ROP of rac-b-BL and rac-lactide using 1, 2, and 5,
we investigated the copolymerization of these monomers to
see if our systems could produce high molecular weight, con-
trolled copolymer materials. As a comparison, Sn(Oct)2, well
known for its use in the production of high molecular weight
PLA on an industrial scale,50 was used as the initial probe
for the copolymerization of rac-lactide and rac-b-BL to serve
as an additional benchmark to our studies using the Al-salen
and salan complexes. With Sn(Oct)2, only atactic PLA was
isolated unless the copolymerizations were conducted under
bulk conditions at 120 ꢀC. In this case, an atactic-poly(lactic
acid)-co-atactic-poly(3-hydroxybutyrate) was isolated with a
broad PDI of approximately 1.8. Polymerizations conducted
1,000 800
1.10
1,800 1,500 1.04
–
–
–
All polymerizations were conducted with 0.058 mmol of [Al] in 3 mL
of toluene at 70 ꢀC for 24 h using benzyl alcohol to generate the active
alkoxide and function as the chain-transfer agent.
b
Determined by gravimetric analysis after drying under vacuum to con-
stant weight.
c
Calculated by ([M]/[Al]) ꢂ MW (monomer) ꢂ (% conv.) þ MW (end
group).
d
Obtained from SEC (GPC).
for 1 and 2 (Table 3). No significant loss of control was
observed in comparison with polymerizations conducted under
living conditions, as shown by the lack of broadening in PDIs.
Thus, benzyl alcohol serves as an efficient chain-transfer agent
for the Al-salen and Al-salan systems at these loadings. How-
ever, when the monomer loading was increased above 1000
mol eq., no polymerization occurred, as was observed in the
immortal ROP of rac-lactide. Al-salen complex 1 resulted in
similar control to Al-salan complex 2 in the immortal ROP of
rac-b-BL, with PDIs of ꢄ1.09, but was significantly slower to
reach comparable conversions. Monomer conversion of >80%
ꢀ
in neat monomer at 120 C using 1, 2, and 5 also resulted in
the formation of poly(lactic acid)-co-poly(3-hydroxybutyrate).
Poor control was observed for copolymers synthesized using
1 and 5, as evidenced by the broadened PDIs of >1.5, mak-
ing these catalysts comparable to previous copolymerizations
using tin,21 magnesium,22 group 4,13 and aluminum23 com-
plexes. However, using the Al-salan complex 2 in the bulk
copolymerization gave excellent control over molecular
weights and narrow PDIs of ꢄ1.09 (Table 4).
ꢀ
was observed after 24 h at 70 C in toluene for 2, whereas 1
was noticeably slower, reaching conversions of 40–75% in the
same timeframe. Complex 5 was inactive under these condi-
tions, presumably because of the high monomer concentration.
Plots of molecular weight versus [rac-b-BL]/[BnOH] ratio
were linear for 1 and 2 (Fig. 4, Supporting Information Fig.
S5), with a slope that correlated well with the molecular
weight of the monomer at lower ratios of [rac-b-BL]/[BnOH].
Some deviation was observed at higher ratios and this was
attributed to the data being collected over a significantly
large range of chain-transfer agent loadings, along with the
high monomer loading. Slight deviation occurred when 1
was used compared to 2. However, these results represent
the best control and highest ratio of chain-transfer agent:-
complex achieved in an immortal ROP of rac-b-BL with an
Al-based complex reported to date.44,45
FIGURE 4 Plot of Mn versus [rac-b-BL]/[BnOH] for immortal
ROP of rac-b-BL at 70 ꢀC in toluene using 2. Ratios of [rac-b-
BL]/[BnOH] were corrected based upon the percent conversion
of monomer.
Although various aluminum salen23,42,46–48 and salan49 com-
plexes have previously been used in both homopolymeriza-
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TABLE 4 Bulk Copolymerization of rac-b-BL and rac-Lactide
PLA sequences, as evidenced by the loss of the characteristic
heterotactic PLA signals in the 1H NMR spectrum (Support-
ing Information Fig. S6). A further increase in rac-b-BL con-
centration, to a ratio of 6:1 (Table 4, Entry 7), resulted in a
1:2 ratio of PLA:PHB in the copolymer after precipitation.
Regardless of initial monomer feed ratios, the copolymeriza-
tions remained very well controlled, with PDIs consistently
below 1.09. After copolymer work-up, examination of the fil-
trates by 1H NMR spectroscopy showed no evidence of PLA
or PHB homopolymers, and therefore some inconsistencies
in rac-b-BL conversion, in comparison to the molecular
weights of the PHB observed in the copolymer, have been
attributed to potential decomposition of the monomer under
these harsh, high temperature conditions.
Using 2a
e
Tg
PDId (ꢀC)
c
d
Entry [LA]:[b-BL]
PLA:PHBb Mn,th
1:1 (100:100) 3.5:1
Mn
1
2
3
4
5
6
7
a
14,900 20,100 1.09 32.0
16,700 29,400 1.05 43.6
27,000 18,900 1.07 35.5
23,000 29,400 1.07 39.3
13,600 15,800 1.07 17.7
23,900 17,100 1.07 13.6
17,300 14,600 1.05 11.4
2:1 (100:50)
4:1 (200:50)
6:1 (300:50)
1:2 (50:100)
1:4 (50:200)
1:6 (50:300)
9:1
19:1
39:1
1:1
1:1.6
1:2
Polymerizations were conducted neat at 120 ꢀC and with 0.035 mmol
ꢀ
of [Al] using 1 eq. benzyl alcohol to generate the active alkoxide.
Solution copolymerizations were successful at 85 C for com-
b
Ratio of PLA to PHB calculated using 1H NMR spectroscopy through
plexes 2 and 5, although 1 yielded poorly controlled (PDIs
ca. 1.4) homopolymers of PLA and PHB under these condi-
tions. 1H NMR spectroscopic kinetic experiments were con-
ducted to monitor the formation of the copolymer in tolu-
ene-d8 at 85 ꢀC in reactions mediated by 2 and 5 (Fig. 5).
These data show that there is a faster rate of rac-lactide
insertion with respect to the rate of insertion for rac-b-BL. A
slight induction period was observed for the ROP of rac-lac-
tide in this case, as the lactide monomer took about 30 min
to dissolve fully at this lower temperature and, in conjunc-
tion with a 15-min delay between monomer addition and
integration of methyl signals associated with each polymer unit.
c
Calculated by (([M]/[Al]) ꢂ MW (rac-b-BL) ꢂ (% conv.)) þ (([M]/[Al] ꢂ
MW (rac-lactide) ꢂ (% conv.)) þ MW (end groups).
d
Obtained from SEC (GPC)/MALS.
e
DSC run with nitrogen flow rate of 50 mL minꢃ1 and heating parame-
ters of 5 ꢀC minꢃ1 for heating and cooling.
Further study of the copolymerization was performed by
manipulating the initial monomer feed ratios of rac-b-BL and
rac-lactide. From an initial feed ratio of 1:1 (100 eq. of each
monomer), near complete conversion of rac-lactide was
observed while rac-b-BL conversion was significantly lower.
After precipitation, the resulting copolymer possessed a
1
the collection of the first H NMR spectrum, gave rise to the
non-zero intercepts of each of the linear regressions. These
results indicate that the copolymerization of rac-b-BL and
rac-lactide, mediated by these Al-salen and Al-salan com-
plexes, displays a preference for the incorporation of rac-lac-
tide over rac-b-BL, even when the rate of homopolymeriza-
tion of rac-b-BL is significantly greater than that of rac-
lactide.
1
3.5:1 ratio of PLA:PHB as calculated from the H NMR spec-
trum. Moreover, signals typical of highly heterotactic PLA
were observed, indicating the presence of long sequences of
PLA in the copolymer. As the amount of rac-lactide in the
initial feed was increased, the ratio of PLA:PHB in the copol-
ymer increased disproportionately. For example, using a rac-
lactide to rac-b-BL initial feed ratio of 6:1 (Table 4, Entry 4)
resulted in a copolymer possessing a 39:1 PLA:PHB ratio.
Again, a strong presence of heterotactic PLA was observed.
Increasing the proportion of rac-b-BL in the initial feed to
four times the rac-lactide concentration (rac-LA:rac-b-BL ¼
50:200, Table 4, Entry 6) resulted in greater PHB incorpora-
tion into the copolymer (1:1.2 ratio) and a loss of the long
Analysis of the phase transitions of these poly(lactic acid)-
co-poly(3-hydroxybutyrate) materials by DSC showed no
phase separation between PLA and PHB segments of the
copolymers, even with the presence of lengthy heterotactic
PLA segments. The DSC thermograms show only a single
glass transition temperature (Tg) ranging from 11.4 ꢀC for a
FIGURE 5 Plots of ln([M]0/[M]t) versus time (min) for the copolymerization of rac-b-BL and rac-lactide by 2 (left) and 5 (right) at 85
ꢀC in toluene-d8 with [rac-b-BL]:[rac-lactide]:[Al] of 50:50:1.
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2 A.-C. Albertsson, I. K. Varma, Biomacromolecules 2003, 4,
1466–1486.
poly(lactic acid)-co-poly(3-hydroxybutyrate) copolymer with
a 1:2 ratio of PLA:PHB to 43.6 ꢀC for a poly(lactic acid)-co-
poly(3-hydroxybutyrate) copolymer containing a 9:1 ratio of
PLA:PHB. As expected, increased PLA content in the copoly-
mer results in an increase in the Tg, whereas increased PHB
content lowers the Tg (Table 4). No melting or crystallization
temperatures were visible in any of the copolymer samples,
confirming that each of the copolymers were amorphous in
nature.
3 H. Seyednejad, A. H. Ghassemi, C. F. van Nostrum, T. Ver-
monden, W. E. Hennink, J. Control. Release 2011, 152, 168–176.
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5 G. S. Kwon, D. Y. Furgeson, In: Biodegradable polymers for
drug delivery systems. M. Jenkins, ed., Biomedical Polymers,
Woodhead Publishing Ltd., Cambridge, UK, 2007, pp 83–110.
6 J. H. Khan, F. Schue, G. A. George, Polym. Int. 2009, 58,
296–301.
CONCLUSIONS
7 D. G. Abebe, T. Fujiwara, Biomacromolecules 2012, 13,
1828–1836.
We have shown that aluminum-based salen and salan com-
plexes 1, 2, and 5 efficiently mediate the immortal ROP of
rac-lactide up to 10 mol eq. of benzyl alcohol chain-transfer
agent and up to 1000 mol eq. of monomer. Moreover, we
have shown that these complexes are able to form high mo-
lecular weight PHB by the ROP of rac-b-BL, whereas previ-
ous reports of rac-b-BL ROP using aluminum salen com-
plexes were only able to access low molecular weight
oligomers. The aluminum salan complex 2 demonstrates par-
ticular efficacy at controlling the ROP of rac-b-BL under a va-
riety of polymerization conditions. Complexes 1 and 2 also
facilitate the immortal ROP of rac-b-BL up to an excess of 50
mol eq. of benzyl alcohol before any loss of control is
observed. When used in the copolymerization of rac-lactide
and rac-b-BL, the aluminum salen complexes 1 and 5 were
unable to provide control under thermally demanding condi-
tions; however, the aluminum salan complex 2 allowed
access to gradient poly(lactic acid)-co-poly(3-hydroxybuty-
rate) copolymers with narrow polydispersities of <1.1, to
the best of our knowledge, an unprecedented result. Com-
plexes 5 and 2 also mediate the formation of well-controlled
8 Y. Li, G. A. Thouas, Q.-Z. Chen, RSC Adv. 2012, 2, 8229–8242.
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ꢀ
poly(lactic acid)-co-poly(3-hydroxybutyrate) at 85 C in tolu-
19 M. Zintl, F. Molnar, T. Urban, V. Bernhart, P. Preishuber-
Pfluegl, B. Rieger, Angew. Chem. Int. Ed. 2008, 47, 3458–3460.
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of rac-lactide over rac-b-BL, with long segments of PLA
formed unless at least a fourfold excess of rac-b-BL is pres-
ent in the initial monomer feed. The initial thermal studies
of these poly(lactic acid)-co-poly(3-hydroxybutyrate) materi-
als show a single Tg, indicating that no phase separation
occurs between the segments of PLA and PHB. Current
efforts in the group look to expand the monomer scope to
other hydroxyalkanoate polymers with larger hydrophobicity
differences to PLAs to generate phase separated gradient
materials.
20 A. Le Borgne, N. Spassky, Polymer 1989, 30, 2312–2319.
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ACKNOWLEDGMENTS
27 T. M. Ovitt, G. W. Coates, J. Polym. Sci. Part A: Polym.
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The authors thank the Natural Sciences and Engineering
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Foundation for Innovation (CFI), Atlantic Canada Opportunities
Agency, the University of Prince Edward Island, and the Univer-
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