Ring-opening of lactides and related cyclic monomers by triaryltin(IV) alkoxides and amides

Article abstract of DOI:10.1039/b102896k

Ar₃SnX, where Ar = p-MeC₆H₄, p-CF₃C₆H₄ or Ph and X = OBu^t or NMe₂, are catalyst precursors for the ring-opening of lactides in benzene at 80°C and the rate of ring-ope

Full text of DOI:10.1039/b102896k

Ring-opening of lactides and related cyclic monomers by triaryltin(IV
)
alkoxides and amides†
Malcolm H. Chisholm* and Ewan E. Delbridge
Department of Chemistry, The Ohio State University, 100 W 18th Avenue, Columbus Ohio, 43210-1185,
USA. E-mail: chisholm@chemistry.ohio-state.edu
Received (in Cambridge, UK) 29th March 2001, Accepted 5th June 2001
First published as an Advance Article on the web 27th June 2001
Ar3SnX, where Ar = p-MeC6H4, p-CF3C6H4 or Ph and X =
OBut or NMe2, are catalyst precursors for the ring-opening
of lactides in benzene at 80 °C and the rate of ring-opening
of lactides and a variety of related cyclic monomers is
influenced by Ar and X such the chemistry of the ring-
opening event and the initially formed product may be
examined.
The compounds Ar3SnX were prepared from either meta-
thetic reactions involving the respective Ar3SnCl compound
and LiNMe2 or by an alcoholysis reaction involving
Ar3SnNMe2 and ButOH in hydrocarbons.‡ The compounds are
white, hydrocarbon-soluble, microcrystalline materials with the
exception of (p-MeC6H4)3SnNMe2 which is a colorless oil.
These compounds were characterized by 1H, 13C{H} and 119Sn
NMR spectroscopy (and for Ar = p-CF3C6H4 by 19F) together
with mass spectrometry, IR spectroscopy and elemental analy-
sis. These compounds were found to be kinetically inert at 80 °C
in benzene, conditions under which ring-opening polymeriza-
tion (ROP) of lactides was subsequently studied.
The ring-opening polymerization of lactides (
L
,
D, rac and
meso) by well-defined coordination complexes is a topic of
current interest since polylactides (PLAs) have numerous
applications ranging from bulk packing materials1 to drug
delivery reagents,2 artificial sutures2,3 and scaffolds4 for tissue
engineering. There have been some exciting recent reports
documenting stereoselective polymerization of rac- and meso-
lactides to give heterotactic, isotactic and syndiotactic PLAs.5
Much remains to be learned at this time, however, since very
little is known about the details of factors controlling the rate of
ring-opening, the stereoselectivity of this event and the
deleterious side reactions of both intra- and inter-chain transfer
and transesterification reactions, which can lead to loss of
control of stereochemistry and molecular weight of PLAs. For
example, the b-diiminate complex [(BDI)Zn(OPri)]2 shown in
A is reported to give > 90% heterotactic PLA from rac-lactide
In a typical polymerization reaction 50 equivalents of lactide
was allowed to react with the Ar3SnX compound in C6D6 at
80 °C (or in some instances at 52, 67 and 70 °C) and the reaction
was monitored with time by NMR spectroscopy. Reactions
were quite slow requiring ca. 3 days to approach 90%
conversion. From the plots of 2ln(A/A0) vs. time (where A =
concentration of lactide) we can estimate the rates of consump-
tion of lactide to be kobs = 2.8(1) 3 1026 and 2.0(1) 3 1026 s21
for X = NMe2 and Ar = p-CF3C6H4 and Ph, respectively. In
reactions between Ph3SnOBut and
-lactide, we can also obtain
L
a reasonable estimate of the rate of the initial ring-opening
event, kro = 2.8(1) 3 1026 s21 which is faster than the rate of
propagation kprop = 1.4(1) 3 1026 s21. From studies of the
rates of polymerization reactions with temperature we have
obtained estimates of the enthalpy and entropy of activation for
the ring-opening event for Ar = Ph and X = NMe2 at a
[lactide]:[catalyst] ratio of 50 to 1: DH‡ = 12(1) kcal mol21 and
DS‡ = 251(5) cal K21 mol21. The rather large entropy of
activation is consistent with a bimolecular reaction with a
highly ordered transition state. However, the role of solvation
has not been examined. It is noteworthy that these polymeriza-
tion reactions are slower than those recently reported for a tin(II
)
catalyst system employing (BDI)SnOPri8 as an initiator and
also that whereas the latter shows a preference for heterotactic,
rmr and mrm, tetrads in the polymerization of rac-lactide, no
such preference is found in reactions employing Ar3SnX
precursors. The rate of polymerization is probably influenced
by the relative polarity of the Sn–OR bond which is greater for
at 25 °C in CH2Cl25c whereas the related magnesium complex
gives atactic polymer under similar conditions with rapid
transesterification.6
The stereocontrol in the polymerization of rac-lactide by
[(BDI)Zn(OPri)]2 has been attributed to end-group control
which is fostered by the bulky BDI ligand, yet even bulkier
Sn(II) than Sn(IV) but, given the relative size of Sn(II) vs. Sn(IV
)
(0.69 Å),9 the stereoselectivity attributed to end-group control
involving the SnOC*HMeC(O)OC*HMeC(O)OP unit of the
growing polymer chain must arise from the pocket created by
the two 2,6-diisopropylphenyl ligands in the (BDI)M(OR)
catalyst systems.
ligands such as pyrazolylborate LMOR complexes [L
=
(3-Butpz)3BH, M = Mg and Zn] show little stereoselectivity.7
We reasoned that much might be learned from studies of the
kinetics of reactions employing Ar3SnOR catalyst precursors
since, unlike trispyrazolylborate ligands or other tridentate
ligands, reversible bond breaking is not likely for the Sn–C and
Sn–O bonds under mild conditions. Moreover the influence of
electronic and steric factors can be examined by the use of para-
and meta-substituents on the aryl ligands. We report here on
initial findings from studies involving Ar3SnX precursors,
where Ar = p-MeC6H4, p-CF3C6H4 or Ph and X = OBut or
NMe2.
Although the Ar3SnX precursors are kinetically inert at 80 °C
in benzene-d6 for several days and the system that is initially
active in the polymerization can be reasonably represented by
Ar3Sn(OP), where OP represents the growing polymer chain,
with the onset of polymerization, Ar4Sn compounds are formed
(as identified by 1H, 13C and 119Sn NMR as well as electrospray
mass spectrometry). Ar4Sn compounds are inactive and the
systems that are believed to be catalytically active are
Ar32nSn(OP)n, where n = 1 or 2. The formation of Ar4Sn
clearly implicates the facility of chain transfer and, in addition,
from studies of molecular weight distributions with time, we
† Electronic supplementary information (ESI) available: additional experi-
mental data. See http://www.rsc.org/suppdata/cc/b1/b102896k/
1308
Chem. Commun., 2001, 1308–1309
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b102896k

In conclusion, these initial studies reveal that this seemingly
most simple system for ring-opening polymerization of lactide
is complicated by mischievous side-reactions. Insight into the
latter, namely ligand exchange and transesterification and the
ring-opening event can be gleaned from studies of model
reactions such as those shown in reactions (1), (2) and (3).
We thank the Department of Energy, Office of Basic Science,
Chemistry Division for financial support.
Notes and references
‡ General considerations: the synthesis of R3SnNMe2 and Ph2Sn(NMe2)2
complexes was based on the reported synthesis11 of Ph3SnNMe2 and
Ph2Sn(NMe2)2. See ESI for additional spectroscopic data.†
SnPh3[OCHMeC(O)OCHMeC(O)NMe2]: dH(400 MHz, C6D6): 0.99 [d,
CHMeC(O)NMe2, 3H], 1.53 (d, SnOCHMe, 3H), 2.11 (s, NMe2, 3H), 2.47
(s, NMe2, 3H), 4.75 (q, SnOCHMe, 1H), 4.83 [q, CHMeC(O)NMe2, 1H],
7.16 (m, m- and p-H, 9H), 7.80 (dd, o-H, 6H, JHH 7.9, 1.5 Hz, 119/117Sn
satellites JSnH 117Sn 64, 119Sn 49 Hz).
SnPh2[OCHMeC(O)NMe2]2: dH(400 MHz, C6D6): 1.43 (d, SnOCHMe,
6H), 1.87 (s, NMe2, 6H), 2.26 (s, NMe2, 6H), 4.87 (q, SnOCHMe, 2H), 7.21
(t, p-H, 2H), 7.35 (t, m-H, 4H), 8.37 (dd, o-H, 4H, JHH 7.6, 1.2 Hz, 119/117Sn
satellites JSnH 117Sn 75, 119Sn 59 Hz).
SnPh3[OCMe2C(O)OCHMeC(O)NMe2]: dH(500 MHz, C6D6): 1.06 (d,
CHMeCONMe2, 3H), 1.56 (s, SnOCMe2, 3H), 1.65 (s, SnOCMe2, 3H), 2.12
(s, NMe2, 3H), 2.47 (s, NMe2, 3H), 4.87 [q, CHMeCO)NMe2, 1H], 7.17 (m,
p-H, 3H), 7.23 (m, m-H, 6H), 7.87 (dd, o-H, 6H, JHH 8.2, 1.3 Hz, 119/117Sn
satellites JSnH 117Sn 64, 119Sn 48 Hz).
Scheme 1
observe extensive transesterification. Thus, even the seemingly
simple and kinetically slow system for the ROP of lactides
employing Ar3SnX precursors has proved to be complicated.
One important point to emerge from these studies is the rate
of ring-opening of lactide and related monomers occurs much
more rapidly when X = NMe2 than for X = OBut. Thus, at
room temperature, Ph3SnNMe2 in benzene ring-opens the
cyclic oxygenates shown in Scheme 1. The regiochemistry of
the ring-opening event can be reliably determined from NMR
studies.‡ The Sn–O13C carbon shows coupling to 119Sn and the
amide methyl protons appear as two singlets due to the
restricted rotation about the C–NMe2 bond. Notable here is the
ring-opening of propylene carbonate (PC) to give 1 and 2
(Scheme 1) a required step in the ring-opening decarbonation
polymerization of PC by tin catalysts at higher tempera-
tures.10
The ring-openings shown in Scheme 1 convert an Sn–NMe2
group to an Sn–OR group and at 25 °C no further insertion/ring-
opening occurs. The compounds are, however, not indefinitely
persistent in solution. The compound Ph3SnOCHMeC(O)OCH-
MeCONMe2 3 which we can represent as Ph3Sn[OCHMe-
C(O)]2NMe2 is labile to transesterification reactions as repre-
sented by eqn. (1).
Polymerization reactions: standard solutions of the appropriate R3SnX
complex (0.027 M) and L- or rac-lactide (0.338 M) were prepared in C6D6
and stored in a dry-box. Aliquots (100, 50, 25 and 12.5 mL for 25+1, 50+1,
100+1 and 200+1, respectively) of R3SnX solutions were transferred along
with an aliquot (200 mL) of either L
- or rac-lactide to a J. Young® NMR
tube. The total volume was made up to 800 mL with C6D6 to ensure a
constant lactide concentration (0.084 M). Rates of polymerization were
determined from 1H NMR data where the sum of the area of monomer and
polymer peaks (CH and CH3) was assumed to be 100% and rates of
disappearance of monomer were calculated by the subtraction of the integral
of the polymer peaks from the integral of the monomer peaks and dividing
by the concentration of monomer at t = 0. The natural log of this ratio was
then plotted against time with a straight line being indicative of pseudo-first
order kinetics. The gradient of this plot was used to determine values of
kobs
.
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Ph3Sn[OCHMeC(O)]2NMe2 ? Ph3Sn[OCHMeC(O)]NMe2 +
Ph3Sn[OCHMeC(O)]nNMe2 (n ! 3) (1)
Reaction (1) is also accompanied by chain transfer and
phenyl migration yielding Ph4Sn. The compound Ph3Sn[OC-
Me2C(O)OCHMeC(O)NMe2] 4 is less labile to transesterifica-
tion of the type shown in eqn. (1), presumably because of the
bulky gem-dimethyl group, but still enters into chain/aryl group
transfer. However, 4 does react with Ph3Sn(OBut) to give
Ph3SnOCHMeC(O)NMe2 and Ph3Sn[OCMe2C(O)OBut], prod-
ucts of transesterification. Ph3SnOCHMeC(O)NMe2 is formed
from the reaction between Ph3SnNMe2 and lactide (2+1 ratio) in
benzene as the major kinetic product in eqn. (2).
Ph3Sn[OCHMeC(O)OCHMeC(O)NMe2] + Ph3SnNMe2 ?
2Ph3Sn[OCHMeC(O)NMe2] (2)
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Reactions employing Ph2Sn(NMe2)2 and lactide (1+1 ratio)
yield Ph2Sn[OCHMeC(O)NMe2]2 by consecutive ring-opening
of lactide followed by intramolecular attack on the chain, eqn.
(3).
Ph2Sn(NMe2)[OCHMeC(O)OCHMeC(O)NMe2] ?
Ph2Sn[OCHMeC(O)NMe2]2 (3)
11 K. Jones and M. F. Lappert, J. Chem. Soc. A, 1965, 1944.
Chem. Commun., 2001, 1308–1309
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