Titanium pyridonates and amidates: Novel catalysts for the synthesis of random copolymers

Article abstract of DOI:10.1039/c2cc37201k

A series of pyridonate and amidate supported titanium alkoxides have been isolated. These complexes can be readily prepared in high yield, under mild reaction conditions in only two steps from commercially available (Ti(NMe ₂)₄). We

Full text of DOI:10.1039/c2cc37201k

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Titanium pyridonates and amidates: novel catalysts for
the synthesis of random copolymers†
Ruth L. Webster,a Nazbanoo Noroozi,b Savvas G. Hatzikiriakos,b Jaclyn A. Thomsona
and Laurel L. Schafer*a
Cite this: Chem. Commun.,
2013, 49, 57--59
Received 2nd October 2012,
Accepted 29th October 2012
DOI: 10.1039/c2cc37201k
www.rsc.org/chemcomm
A series of pyridonate and amidate supported titanium alkoxides have copolymer formation have been realised with designed catalysts.6
been isolated. These complexes can be readily prepared in high yield, Exploring catalyst structure/polymer properties is of fundamental
under mild reaction conditions in only two steps from commercially importance to our understanding of copolymerisations and realis-
available (Ti(NMe2)4). We have furnished one of the rare examples of ing their potential in real-life applications.
discrete catalysts for random copolymer synthesis.
We have previously reported the synthesis of bis(pyridonate)-
and bis(amidate)-metal-amido complexes of the Group 4 transition
There have been great advances in the initiator systems available for metals as excellent precatalysts for the catalytic synthesis of
the ring-opening polymerisation (ROP) of lactide (LA) and caprol- amines.7–10 However, Group 4 pyridonate and amidate complexes
actone (CL), including systems that produce very high molecular have not yet been explored for their potential in ROP. Yttrium
weight polymers and exhibit exquisite LA-stereocontrol under amidate complexes on the other hand have been exploited in this
ambient conditions.1 Titanium catalysts have not, as yet, shown role,11 whereby trisligated complexes have been shown to produce
such high levels of reactivity and control during polymerisation. high molecular weight PCL.11a However, the moisture sensitivity of
Although Ti-mediated homopolymerisations cannot yet compete such yttrium initiators is a limitation to their application toward
with alternative metal initiators, the low toxicity2 of titanium makes scalable, functionalised polymer synthesis. Pyridonate or amidate
it attractive for the synthesis of copolymers with potential titanium alkoxides could provide an alternative robust platform for
biomedical application.3 For example, high molecular weight investigating ligand stereoelectronic effects upon ROP, combined
homopolymer for application in drug-delivery materials can result with the desirable bio-compatibility of titanium (Scheme 1).
in poor biodegradation or detrimental ‘‘bursts’’ of drug release.4
¨ ¨
Synthesis of bis(pyridonate)- or bis(amidate)-titanium-
Seppala and co-workers have shown that random copolymers bis(dialkylamido) complexes is facile, by reaction of neutral amide
offering alternative mechanical properties to traditional homo- or pyridone proligands with commercially available transition metal
polymers can be advantageous for such specialised applications.4b,5 tetrakis(dialkyl)amido complexes at room temperature.7 However,
PLA, characterised as hard and brittle with low maximum strain, synthesis and rigorous characterisation of the related alkoxides has
and PCL, known to be tough with high maximum strain, can be thus far remained elusive, likely due to complex aggregate formation
combined into copolymers offering high levels of strain yet a range during attempted reactions of Ti(OiPr)4 with pyridonate and amidate
of physical properties ‘‘from weak elastomers to tougher thermo- proligands. However, we were pleased to find that a sequential
plastics’’.5b As a result blends, block or random copolymers of PLA protonolysis approach, by reaction of Ti(NMe2)4 with proligand,
and PCL may offer a desirable, tunable combination of properties followed by reaction with isopropanol in one pot, furnishes a range
suitable for a range of applications in biomedical science. While of pyridonate- or amidate-titanium-alkoxides in excellent yield.12
copolymerisations are an intense area of investigation with a range
of metal centres,3,6 such reactivity with discrete titanium initiators
has rarely been reported.6a Indeed very few examples of random
a Department of Chemistry, The University of British Columbia, 2036 Main Mall,
Vancouver, BC V6T 1Z1, Canada. E-mail: schafer@chem.ubc.ca;
Fax: +1-604-822-2847; Tel: +1-604-822-9264
b Department of Chemical and Biological Engineering, The University of British
Columbia, 2360 East Mall, Vancouver, BC V6T 1Z3, Canada
† Electronic supplementary information (ESI) available: Experimental details
Scheme 1 Synthesis of pyridonate- and amidate-supported titanium-alkoxides
and full spectroscopic analysis data. CCDC 882572. For ESI and crystallographic
data in CIF or other electronic format see DOI: 10.1039/c2cc37201k
and their application in polymerisation.
c
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Table 1 Melt-phase homopolymerisation of rac-LA and e-CL
Entry Cat. Monomer Yielda (%) Mn (g molÀ1) Mntheoc,12 PDIb Pm
b
d
1
2
3
4
5
6
7
1
2
3
4
5
1
2
3
4
5
LA
88
90
81
95
93
98
98
96
98
85
13 800
14 120
22 220
23 040
25 440
39 400
22 810
21 360
20 860
27 470
19 030
19 460
17 510
20 540
20 110
16 780
16 780
16 440
16 780
14 550
1.17 0.49
1.21 0.46
1.22 0.46
1.17 0.55
1.16 0.53
CL
1.29
1.38
1.28
1.48
1.33
—
—
—
—
—
Fig. 1 Pyridonate- and amidate-titanium-alkoxides 1–5 were synthesised in high yield
from Ti(NMe2)4. Right: ORTEP representation of the solid state molecular structure of
1, thermal ellipsoids set at 50%, selected bond lengths (Å) Ti–O1 2.003(1),
Ti–O2 1.986(1), Ti–N1 2.219(1), Ti–N2 2.250(2), Ti–O3 1.785(1), Ti–O4 1.766(1),
C1–O1 1.318(2), C1–N1 1.344(3), C7–O2 1.325(2), C7–N2 1.347(2) and angles (1)
N1–Ti–O1 62.72(5), N2–Ti–O2 62.51(5), N1–C1–O1 111.8(2), N2–C7–O2 111.5(2).
8e
9f
10e,g
PLA: 130 1C, 24 h, [LA]/[Ti] = 300, 0.5 g. PCL: 100 1C, 16 h, [CL]/[Ti] = 300,
c
0.5 ml. a Isolated yield. b Determined by GPC. Mntheo = ([M]/2[Ti] Â
e
f
g
%Yield  MW). d 1H{1H} NMR spectrum. Bimodal GPC trace. 1 h. 2 h.
To the best of our knowledge, these are the first examples
of fully characterised and mononuclear pyridonate- and amidate-
titanium-alkoxides (Fig. 1).
intriguing facet is the increase in PLA Mn on moving from
6-methyl-pyridonate, 1, to 3-methyl-pyridonate, 2, which is
further enhanced when 3, with a bulkier substituent in the
3-position, is employed. This trend is reversed during PCL
synthesis (compare entries 6, 7 and 8): we questioned whether
this tunability during homopolymerisations coupled with the
unusual ability to afford efficient PLA and PCL formation could
be exploited for the synthesis of random copolymers.
6-Methyl-, 3-methyl- and 3-phenyl-pyridonate complexes
(1, 2 and 3) have been synthesised in the first instance to provide
a direct comparison of steric bulk adjacent to nitrogen versus the
oxygen heteroatom. Crystals of 1 can be grown from hexanes at
À30 1C and it can be seen that the ligand binds unsymmetrically
through the N,O chelate.12 The Ti–O1 and Ti–N1 bond lengths
are 2.003(1) Å and 2.219(1) Å respectively. Such asymmetric
binding modes have been previously reported for pyridonate
group 4 bis(dialkylamido) complexes,13 but are in contrast to
previously reported bis(amidate)-bis(dialkylamido) complexes
(vide infra).8 The robust nature of these complexes is astonish-
ing; heating complexes 1 to 3 in refluxing ethanol for up to 64 h
does not result in ligand protonolysis and precipitation of Ti
oxides as may be expected, instead the pyridonate ligand
remains coordinated to the metal.12 The highly sterically hin-
dered amidate alkoxides 4 and 5 also form readily, but 5 shows
To date, few examples of well-characterised initiators are known
to facilitate the copolymerisation of LA and CL,6 and the present
state-of-the-art is Al Schiff-base or salen complexes.6d,f Examples of
CL/LA random copolymers where there is a 1 : 1 incorporation of
both monomers are rare simply because there is a propensity for LA
to polymerise first, followed by CL incorporation at a lower rate.16
Alternatively, an initiator which facilitates randomisation through
transesterification can be used, thus avoiding this formation of
block-like polymers, instead resulting in short average sequence
lengths17 (an ideal random copolymer will have LCL = LLL = 216a,6d).
Complexes 1, 2 and 3 form random copolymers in excellent yield
using a low catalyst loading compared to leading salan/salen
examples.6b,d We also observe excellent levels of CL and LA incor-
poration without the need for an excess CL feed. Mn is competitive
with previously reported values using well-defined initiators with a
1 : 1 monomer feed (e.g. 22 320 using initiator 3 vs. 13 900,6b
16 300,6c and 21 6006d), Table 2. An initial attempt to increase the
incorporation of CL into the random copolymer, by moving to
reaction conditions which favour CL homopolymerisation i.e. lower
reaction temperature, did not affect the polymer composition as
hoped, but in fact led to predominantly PLA with only 12% CL
1
broadened signals in the H NMR spectrum at room tempera-
ture, associated with fluxional ligand binding on the NMR time-
scale. Heating the sample to 95 1C results in a simplified NMR
spectrum. Although X-ray quality crystals of these titanium
amidates could not be obtained, characterisation by VT-NMR
spectroscopy and HRMS suggest that discrete monomeric spe-
cies form. This would be consistent with the previously reported
monomeric bis(diethylamido) precursor.8b Interestingly, in the
solid state the diethylamido species is C2 symmetric and exhibits
bond lengths for Ti–Oamidate 2.146(1) Å and Ti–Namidate 2.156(1)
Å, indicating a far more delocalised N,O-chelate than that
exhibited by the pyridonates described above. Considering the
varying steric and electronic attributes of these related ligand
sets, it is interesting to examine their different catalytic activities.
We first investigated the homopolymerisation of LA and CL
using catalysts 1 to 5 in the melt state (Table 1). As anticipated
Mn and PDIs are modest compared to alternative metal initia-
tors,1 but are competitive with leading Ti examples.14,15 Differ-
ences between observed and theoretical Mn (Mntheo) may be
consistent with transesterification processes.12 Some PLA
Table 2 Melt-phase copolymerisation of e-CL and rac-LA
Yielda CL/LAb LCL
/
Mn
(g molÀ1 d
Mntheoe, 12
c
Entry Catalyst
(%)
(mol%) LLL
)
(g molÀ1
)
PDId
1
2
3
4
5
6
1
1f
2
3
4
5
82
60
83
86
68
63
45/55
29/71
52/48
43/57
64/36
5/95
1.8/3.4 18 750
28 780
1.9/2.9 19 070
1.7/3.5 22 320
3.1/2.4 19 190
19 600
20 320
19 280
19 690
18 740
21 400
1.41
1.36
1.29
1.38
1.37
1.38
—
—
23 660
chain-end stereocontrol is observed and it is interesting to note Conditions: 130 1C, 24 h, [monomer]/[Ti] = 600, 0.5 g (3.45 mmol) LA,
a
b
0.38 ml (3.45 mmol) CL. Isolated yield. Ratio of CL/LA determined
the shift in stereocontrol in moving from pyridonate initiators 2
and 3, where there is an isotactic bias, to amidates 4 and 5
by 1H NMR. Average chain length determined by 13C{1H} NMR.
c
d
e
Values determined by GPC analysis. Mntheo = ([CL]/2[Ti] Â %CL
Â
f
where there is a slight preference for heterotacticity. Another 114.14) + ([LA]/2[Ti] Â %LA Â 144.13). 100 1C, 18 h, then 130 1C, 7 h.
c
58 Chem. Commun., 2013, 49, 57--59
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for use of GPC instrumentation and Parisa Mehrkhodavandi for
helpful discussion. This research was undertaken, in part,
thanks to funding from the Canada Research Chairs program.
Notes and references
1 For an overview see: (a) M. Labet and W. Thielemans, Chem. Soc.
Rev., 2009, 38, 3484; (b) R. H. Platel, L. M. Hodgson and
C. K. Williams, Polym. Rev., 2008, 48, 11; (c) J. Wu, T.-L. Yu,
C.-T. Chen and C.-C. Lin, Coord. Chem. Rev., 2006, 250, 602;
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2 D. M. Brunette, P. Tengvall, M. Textor and P. Thomsen, Titanium in
Medicine: Materials Science, Surface Science, Engineering, Biological
Responses and Medical Applications, Springer, 2001.
Fig. 2 (a) Reaction profiling the consumption of LA ( ) and CL ( ) during
copolymerisation; (b) monitoring the presence of LA homodiads ( ),
CL homodiads ( ) and heterodiads (Â) over time.
3 (a) Polymers for Biomedical Application, ed. A. Mahapataro and
A. S. Kulshrestha, American Chemical Society, 2008; (b) L. S. Nair
and C. T. Laurencin, Prog. Polym. Sci., 2007, 32, 762.
(entry 2). The change from initiator 1 to 2, resulted in a decrease in
PDI and more importantly a reduction in LLL and a decrease in the
LA content (48%). A Tg of À3.3 1C is obtained for copolymer
synthesised using 2, where the theoretical value is À20.8 1C,16 while
Tm was not observed. Pushing the reactivity trends further, to
3-phenyl-pyridonate 3, results in an increase in Mn, but a return
to higher levels of LA incorporation. Although the yield with initiator
4 is modest, an unusual preference for CL incorporation is observed.
In contrast, PLA dominates when bulkier amidate complex 5 is
employed.
¨ ¨
4 (a) J. Rich, T. Karjalainen, L. Ahjopalo and J. Seppala, J. Appl. Polym.
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Sci., 2002, 86, 1; (b) T. Karjalainen, J. Rich and J. Seppala, J. Appl.
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H. Kimura, H. Miyamoto, Y. Honda and Y. Ikada, J. Controlled
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5 (a) N. Ahola, J. Rich, T. Karjalainen and J. Seppala, J. Appl. Polym.
Sci., 2003, 88, 1279; (b) M. Hiljanen-Vainio, T. Karjalainen and
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J. Seppala, J. Appl. Polym. Sci., 1996, 59, 1281.
6 (a) D. Dakshinamoorthy and F. Peruch, J. Polym. Sci., Part A: Polym.
Chem., 2012, 50, 2161; (b) Y. Wang and H. Ma, Chem. Commun.,
2012, 48, 6729; (c) D. J. Darensbourg and O. Karroonnirum, Macro-
molecules, 2010, 43, 8880; (d) N. Nomura, A. Akita, R. Ishii and
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L. Annunziata and C. Pellecchia, Macromolecules, 2009, 42, 6056;
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7 R. K. Thomson, J. A. Bexrud and L. L. Schafer, Organometallics, 2006,
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8 (a) Z. Zhang, D. C. Leitch, M. Lu, B. O. Patrick and L. L. Schafer,
Chem.–Eur. J., 2007, 13, 2012; (b) C. Li, R. K. Thomson, B. Gillon,
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Investigation of the carbonyl region of the 13C{1H} NMR
spectrum reveals that all of the copolymers undergo transester-
ification.17 Reaction monitoring of polymerisation catalysed by 3
shows rapid polymerisation of LA to form longer chains of PLA
(6 h: LCL 1.5; LLL 5.7) with CL reacting modestly (Fig. 2a). CL/LA
ratios remain static after 10 h, where there is also a concomitant
increase in the presence of heterodiads (CL–LA bonds), thereby
reiterating the randomising effect of transesterification (Fig. 2b).
After 10 h LLL and LCL reach their final observed values, however, Mn
is 12 550 g molÀ1 and the PDI is 1.48 (compared to 22 320 g molÀ1
9 R. O. Ayinla and L. L. Schafer, Inorg. Chim. Acta, 2006, 359, 3097.
10 J. A. Bexrud, P. Eisenberger, D. C. Leitch, P. R. Payne and
L. L. Schafer, J. Am. Chem. Soc., 2009, 131, 2116.
and 1.38 in the final isolated polymer). This data suggests that the 11 (a) L. J. E. Stanlake, J. D. Beard and L. L. Schafer, Inorg. Chem., 2008,
47, 8062. Bis-ligated examples: (b) F. Zhang, J. Zhang, H. Song and
G. Zi, Inorg. Chem. Commun., 2011, 14, 72; (c) Q. Wang, F. Zhang,
H. Song and G. Zi, J. Organomet. Chem., 2011, 696, 2186.
polymer chain continues to grow after the 10 h time period through
transesterification.18,19 Methanol soluble (i.e. low mass) fractions of
the quenched reaction solutions were subjected to qualitative 12 See ESI†.
13 J. A. Bexrud and L. L. Schafer, Dalton Trans., 2010, 39, 361.
14 Selected rac-LA examples include: (a) A. D. Schwarz, K. R. Herbert,
MALDI-TOF analysis. Low mass cyclic species and short linear
chains composed of half lactide units can be seen. The methyl ester
C. Paniagua and P. Mountford, Organometallics, 2010, 29, 4171;
peak, resulting from methanol-quenched transesterifications, is also
present in the 1H NMR spectrum.12
(b) A. J. Chmura, M. G. Davidson, M. D. Jones, M. D. Lunn,
M. F. Mahon, A. F. Johnson, P. Khunkamchoo, S. L. Roberts and
S. S. F. Wong, Macromolecules, 2006, 39, 7250; (c) S. Gendler,
S. Segal, I. Goldberg, Z. Goldschmidt and M. Kol, Inorg. Chem.,
2006, 45, 4783; (d) C. K. A. Gregson, I. J. Blackmore, V. C. Gibson,
N. J. Long, E. L. Marshall and A. J. P. White, Dalton Trans., 2006,
3134; (e) M. H. Chisholm, C. C. Lin, J. C. Gallucci and B. T. Ko,
Dalton Trans., 2003, 406; ( f ) Y. Kim, G. K. Jnaneshwara and
J. G. Verkade, Inorg. Chem., 2003, 42, 1437.
In conclusion, novel bis(pyridonate)- and bis(amidate)-titanium-
alkoxides have been isolated in excellent yield. All can be prepared
under mild reaction conditions from a common precursor,
Ti(NMe2)4. The complexes have been used in the polymerisation
of LA and CL and are the first examples of polymerisation initiated
by this class of titanium compound. Most importantly, these
titanium initiators can be used for copolymer synthesis with short
sequence lengths, close to 1 : 1 monomer incorporation and good
Mn due to transesterification. We plan to further exploit our
synthesis of random copolymers with these readily modified ligand
15 Selected e-CL examples include: (a) D. Dakshinamoorthy and
F. Peruch, J. Polym. Sci., Part A: Polym. Chem., 2012, 49, 5176;
(b) A. D. Schwarz, A. L. Thompson and P. Mountford, Inorg. Chem.,
2009, 48, 10442; (c) J. Cayuela, V. Bounor-Legare, P. Cassagnau and
A. Michel, Macromolecules, 2006, 39, 1338; (d) A. J. Chmura,
M. G. Davidson, M. D. Jones, M. D. Lunn and M. F. Mahon, Dalton
Trans., 2006, 887.
sets to access a family of polymerisation catalysts affording a large 16 (a) Y. Gnanou and M. Fontanille, Organic and Physical Chemistry of
Polymers, Wiley, USA, 2008; (b) J. M. Vion, R. Jerome, P. Teyssie,
M. Aubin and R. E. Prudhomme, Macromolecules, 1986, 19, 1828.
17 J. Kasperczyk and M. Bero, Makromol. Chem., 1993, 194, 913.
scope of Mn, sequence length and level of transesterification. Such
synthetic results, polymer characterization and rheological investi-
gations will be reported shortly.
18 (a) H. R. Kricheldorf, K. Bornhorst and H. Hachmann-Thiessen,
Macromolecules, 2005, 38, 5017; (b) P. Vanhoorne, P. Dubois,
R. Jerome and P. Teyssie, Macromolecules, 1992, 25, 37.
19 It can be assumed that transesterification continues to proceed after
10 h because there is no significant change in the LLL and LCLvalues.
NSERC and NOVA Chemicals Corporation are acknowledged
for financial support of this work. RLW thanks the Government
of Canada for a Commonwealth PDRF. We thank Derek P. Gates
c
This journal is The Royal Society of Chemistry 2013
Chem. Commun., 2013, 49, 57--59 59