Synthesis of Polycaprolactone

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CRITICAL REVIEW
www.rsc.org/csr | Chemical Society Reviews
Synthesis of polycaprolactone: a revieww

Marianne Labet and Wim Thielemans*
Downloaded by University of Memphis on 12 June 2012

Published on 25 September 2009 on http://pubs.rsc.org | doi:10.1039/B820162P
Received 15th January 2009

First published as an Advance Article on the web 25th September 2009
DOI: 10.1039/b820162p
Polycaprolactone (PCL) is an important polymer due to its mechanical properties, miscibility
with a large range of other polymers and biodegradability. Two main pathways to produce
polycaprolactone have been described in the literature: the polycondensation of a
hydroxycarboxylic acid: 6-hydroxyhexanoic acid, and the ring-opening polymerisation (ROP) of a
lactone: e-caprolactone (e-CL). This critical review summarises the dierent conditions which have
been described to synthesise PCL, and gives a broad overview of the dierent catalytic systems
that were used (enzymatic, organic and metal catalyst systems). A surprising variety of catalytic
systems have been studied, touching on virtually every section of the periodic table. A detailed list
of reaction conditions and catalysts/initiators is given and reaction mechanisms are presented
where known. Emphasis is put on the ROP pathway due to its prevalence in the literature and the
superior polymer that is obtained. In addition, ineective systems that have been tried to catalyse
the production of PCL are included in the electronic supplementary information for completeness
(141 references).
Introduction
Polycaprolactone (PCL) is an aliphatic polyester composed of
hexanoate repeat units. It is a semicrystalline polymer with a
degree of crystallinity which can reach 69%.1 The unit cell is
orthorhombic and the lattice constants are a = 7.496 0.002 A,
b = 4.974 0.001 A and c = 17.297 0.023 A, c being the
Driving Innovation in Chemistry and Chemical Engineering,

School of Chemistry-Faculty of Science and Process and
Environmental Research Division-Faculty of Engineering,
The University of Nottingham, University Park, NG7 2RD,
United Kingdom. E-mail: Wim.Thielemans@nottingham.ac.uk
w Electronic supplementary information (ESI) available: Tables of all
reaction systems and compounds. See DOI: 10.1039/b820162p
Marianne Labet was born in

Angouleme, France, in 1983.
She studied paper and printing
engineering at the Ecole
Francaise de Papeterie et des
Industries Graphiques, INPG
(Grenoble, France) from 2003
to 2006. She obtained her
Masters degree in materials
science in 2006 working under
the supervision of Prof. Alain
Dufresne and Dr Wim
Thielemans. Since 2006, she
has been a PhD student under
the supervision of Dr Wim
Marianne Labet
Thielemans, at the University
of Nottingham where she is working on the use of starch and
cellulose nanocrystals as substrates for the surface initiated
ROP of lactones.
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bre axis.2 The physical, thermal and mechanical properties of

PCL depend on its molecular weight and its degree of crystallinity. Ranges of reported property values are shown in
Table 1.
At room temperature, PCL is highly soluble in chloroform,
dichloromethane, carbon tetrachloride, benzene, toluene,
cyclohexanone and 2-nitropropane; slightly soluble in acetone,
2-butanone, ethyl acetate, dimethylformamide and acetonitrile; and insoluble in alcohols, petroleum ether, diethyl
ether and water.7 PCL displays the rare property of being
miscible with many other polymers (such as poly(vinyl chloride),
poly(styreneacrylonitrile), poly(acrylonitrile butadiene styrene),
poly(bisphenol-A) and other polycarbonates, nitrocellulose
and cellulose butyrate), and is also mechanically compatible
Wim Thielemans obtained a

Masters in Chemical Engineering from the KULeuven,
Belgium in 1999 working under
the supervision of Prof. Jan
Mewis and Prof. Jan Vermant.
He received his PhD in 2004
working with Prof. Richard
Wool (Chemical Engineering,
University of Delaware, USA).
Wim subsequently moved to the
INPG (Grenoble, France) as a
postdoctoral researcher/Marie
Curie research fellow working
with Prof. Alain Dufresne and
Wim Thielemans
Prof. M. Naceur Belgacem.
Since August 2006, Wim has been a lecturer in chemistry and
chemical engineering at the University of Nottingham. His research
interests include the surface modication of starch and cellulose
nanocrystals and their self-assembly.
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Table 1
Properties of PCL
Properties
Range
Ref.
Number average molecular weight

(Mn/g mol1)
Density (r/g cm3)
Glass transition temperature (Tg/1C)
Melting temperature (Tm/1C)
Decomposition temperature (/1C)
Inherent viscosity (Zinh/cm3 g1)
Intrinsic viscosity (Z/cm3 g1)
Tensile strength (s/MPa)
Young modulus (E/GPa)
Elongation at break (e/%)
530630 000
1.0711.200
(65)(60)
5665
350
100130
0.9
4785
0.210.44
201000
1,36
35, 7 and 8
38
9
5
1
3, 5, 6 and 8
3 and 5
1, 3, 5, 6 and 8
with others (polyethylene, polypropylene, natural rubber, poly(vinyl acetate), and poly(ethylenepropylene) rubber).
PCL biodegrades within several months to several years
depending on the molecular weight, the degree of crystallinity
of the polymer, and the conditions of degradation.614 Many
microbes in nature are able to completely biodegrade PCL.6
The amorphous phase is degraded rst, resulting in an increase
in the degree of crystallinity while the molecular weight
remains constant.9 Then, cleavage of ester bonds results in
mass loss.7,14 The polymer degrades by end chain scission
at higher temperatures while it degrades by random chain
scission at lower temperatures (Fig. 1).13 PCL degradation
is autocatalysed by the carboxylic acids liberated during
hydrolysis7 but it can also be catalysed by enzymes,
resulting in faster decomposition.11 While PCL can be
enzymatically degraded in the environment, it cannot be
degraded enzymatically in the body.8
PCL has uses in dierent elds such as scaolds in tissue

engineering,9,1416 in long-term drug delivery systems7,10,11 (in
particular contraceptives delivery8), in microelectronics,17 as
adhesives,13 and in packaging.8 Its wide applicability and
interesting properties (controlled degradability, miscibility
with other polymers, biocompatibility and potential to be
made from monomers derived from renewable sources) makes
PCL a very useful polymer if its properties can be controlled
and it can be made inexpensively. A large number of catalysts
and catalytic systems, spanning virtually the whole periodic
table have been investigated. It is therefore paramount to have
a good understanding and overview of the dierent catalysts
and catalytic systems that have been studied to drive new
developments in catalysis (whether organic-, metal- or
enzyme-based) or chose the appropriate system to obtain the
polymer with the desired characteristics. The former would be
of interest to anyone working on catalysis, whereas the latter is
more directed towards polymer chemists. This review aims
to be a reference work that can be used for this purpose.
Knowledge of ineective systems is of equal importance and
they are described in the ESI.w
Preparation of the monomers

A number of microorganisms oxidise cyclohexanol into adipic
acid (Scheme 1).18 In this process, both e-CL and 6-hydroxyhexanoic acid are intermediary products. Industrially, e-CL
is produced from the oxidation of cyclohexanone by peracetic
acid (Scheme 2).19
Fig. 1 Cleavage of the polymeric chains during the degradation of PCL.
Scheme 1 Oxidation of cyclohexanol to adipic acid in Acinetobacter sp. strain SE19, adapted from Thomas et al.18
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molecular weight and a lower polydispersity. As a consequence,

ROP is the preferred route and will be discussed in more detail
in the following section.
Scheme 2 Production of e-caprolactone from cyclohexanone at Solvay.19
Polymerisation

There are two methods to prepare PCL: the condensation of

6-hydroxycaproic (6-hydroxyhexanoic) acid and the ringopening polymerisation (ROP) of e-CL.
Polycondensation
A large number of patents describe the preparation of aliphatic
polyesters from hydroxycarboxylic acids.2024 Braud et al.25
synthesised PCL oligomers by polycondensation of 6-hydroxyhexanoic acid under vacuumthereby removing the water
produced during the reaction and displacing the equilibrium
towards the formation of the polymer. The reaction was
performed without the addition of catalyst and was complete
in 6 h at a temperature that was gradually increased from 80 to
150 1C.
Polymerisation of 6-hydroxycaproic acid using lipase
from Candida antarctica under vacuum gave rise to
polymers with an average molecular weight of 9000 g mol1
and a polydispersity under 1.5 in 2 days.26 Using lipase
from Pseudomonas sp. at 45 1C to polymerise ethyl
6-hydroxyhexanoate resulted in polymers with an average
molecular weight of 5400 g mol1 and a polydispersity under
2.26 after 20 days with 82% monomer conversion.27 Ethanol
was produced as a byproduct, which inuenced the equilibrium,
but it could be removed under vacuum.
Only a few papers describe the preparation of PCL by
polycondensation in detail. ROP gives a polymer with a higher
Ring-opening polymerisation
1. General mechanisms. Four main mechanisms for the
ROP of lactones exist, and they depend on the catalyst:
anionic, cationic, monomer-activated and coordination
insertion ROP.
a Anionic ROP. Anionic ROP (Scheme 3) involves the
formation of an anionic species which attacks the carbonyl
carbon of the monomer. The monomer is opened at the
acyloxygen bond and the growing species is an alkoxide.28
The main drawback of this method is the occurrence of
signicant intramolecular transesterication, also called
back-biting, in the later stages of the polymerisation. This
results either in low molecular weight polymers, if the
polymerisation is stopped before back-biting can occur, or in
cyclic polymers.
b Cationic ROP. Cationic ROP (Scheme 4) involves the
formation of a cationic species which is attacked by the
carbonyl oxygen of the monomer through a bimolecular
nucleophilic substitution (SN2) reaction.28
c Monomer-activated ROP. Monomer activated ROP
(Scheme 5) involves the activation of the monomer molecules
by a catalyst, followed by the attack of the activated monomer
onto the polymer chain end.30,31
d Coordinationinsertion ROP. Coordinationinsertion
ROP (Scheme 6) is the most common form of ROP. It is
actually a pseudo-anionic ROP. The propagation is proposed
to proceed through the coordination of the monomer to the
Scheme 3 Mechanism of the initiation step for anionic ROP, adapted from Khanna et al.29
Scheme 4
Mechanism of the initiation step for cationic ROP, adapted from Khanna et al.29 and Stridsberg et al.28
Scheme 5 Mechanism of the initiation step for the monomer-activated ROP, adapted from Kim et al.31 and Endo.30
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Scheme 6 Mechanism of the initiation step for coordinationinsertion ROP, adapted from Khanna et al.29 and Stridsberg et al.28

Scheme 7 Intermolecular transesterication reaction during the polymerisation of PCL.
Scheme 8 Intramolecular transesterication reaction during the polymerisation of PCL.
catalyst and the insertion of the monomer into a metaloxygen

bond of the catalyst. During propagation, the growing chain is
attached to the metal through an alkoxide bond.28
2. Transesterication side-reactions. During ROP of e-CL
using an initiator and a catalyst, both intermolecular transesterication (Scheme 7) and intramolecular transesterication
(Scheme 8) can occur as side reactions. These reactions are
generally encountered during the later stages of polymerisation,
particularly at high temperature. It results in broadening of the
polydispersity, and loss of control of the polymerisation.
Catalysts used for ROP and reaction conditions

Three dierent catalytic systems are described: metal-based,
enzymatic, and organic systems (the latter section also mentions
small inorganic acids). A concise representation of all
mentioned systems, and others, can be found in the ESI,w
following the same sequence as the texttheir inclusion in the
body of this manuscript would hamper readability. Published
ineective systems can also be in found in the ESI.w
ROP catalysed by metal-based compounds
Dierent authors use dierent terms to describe the metalbased compounds which take part in the ROP of lactones.
Some authors use catalysts, others use initiators, initiating
systems or catalytic systems. Indeed, the metal-based compound must be regenerated in the termination step to be a true
catalyst, and this does not always occur, thereby keeping the
polymeric chain alive. As a consequence, some people recoil
from calling them catalysts. For the sake of consistency
in this review, we decided to call metal-based compounds
catalysts and alcohols and amines initiators. However,
sometimes, only one compound is used, mainly when a part of
the compound initiates the reaction (generally the alkoxide
part), while another part catalyses it (generally the metal
centre). In this case, the more appropriate term catalyst
initiator is used.
1. Alkali-based catalysts. Alkali metal-based catalysts
(ESIw Table 1.1) showed some activity.32 These catalysts are
ionic compounds and the ROP mechanism is anionic. As a
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consequence, polymerisation is not well controlled due to

transesterication. Moreover, alkali-based compounds
have a tendency to form aggregates, which decreases their
solubility.32
Bhaw-Luximon et al.33 polymerised e-CL in dioxane using
lithium diisopropylamide (LDA, ESIw Table 1.1, entry 1). The
polymerisation is proposed to proceed through an anionic
mechanism (Scheme 9).33 Completion of polymerisation was
reached after only a few minutes at 25 1C and a medium
molecular weight polymer was obtained (Mn = 5700 g mol1
when [e-CL]/[LDA] = 50).
Phenyl lithium (ESIw Table 1.1, entry 2) led to high molecular
weight polymers after a few hours at 170 1C.35 Yuan et al.36
used cyclopentadienyl sodium (ESIw Table 1.1, entry 3) in bulk
and in non-polar solvents to obtain number average molecular
weights up to 130 000 g mol1. In polar solvents, only oligomers
were obtained. No cyclopentadienyl groups were present on the
polymeric chain ends and the polymerisation is said to proceed
through deprotonation of the monomer (Scheme 10).
Mingotaud et al.37 polymerised e-CL with dierent catalysts
in organic solvents and in supercritical carbon dioxide
(scCO2). Tert-butoxyl potassium (ESIw Table 1.1, entry 4)
was one of the catalysts tested. The conversion is lower for
scCO2, indicating the occurrence of side reactions between the
anionic species and carbon dioxide.
2. Alkaline earth-based catalysts. Catalysts based on
alkaline earth metals are very attractive because of their high
activity and low toxicity.32 The most commonly used alkaline
earth metals are magnesium and calcium. Magnesium, the
most abundant alkali earth metal, is essential to plants
and animals, and is therefore biologically benign.38 As a
consequence, it is an interesting metal to use in the synthesis
of polymers for biomedical applications.
Alkyl-containing magnesium complexes (ESIw Table 1.2,
entries 16) resulted in high molecular weight polymers with a
low to moderate polydispersity.39 The polymerisation is said
to be initiated by alkyl transfer into the monomer. Applying
magnesium alkoxide complexes (ESIw Table 1.2, entries 7 and 8)
to the ROP of e-CL gave rise to medium to high molecular
weight polymers (Mn = 6300 to 54 200 g mol1) with low to
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Scheme 9
ROP of e-CL catalysed by LDA.34
Scheme 10 ROP of e-CL catalysed by cyclopentadienyl sodium.36
medium polydispersity (PDI = 1.06 to 1.35).40 The complex

from entry 7 led to faster polymerisation than the catalyst
from entry 8. This was attributed to the steric bulkiness of
complex 8, which sped up the reaction rate. Indeed, more
bulky ligands interact with the initiator and provide a steric
barrier to prevent side reactions.41 The polymerisation is
initiated via insertion of the alkoxy group into the monomer.
Shueh et al.42 investigated a magnesium aryloxide as a
catalyst (ESIw Table 1.2, entry 9). The linear relationship
between the monomer : initiator ratio and the molecular
weight of the polymer suggests a living character to the
polymerisation. No intramolecular transesterication, leading
to the formation of macrocycles, was found to occur.
Like magnesium, calcium is essential to animals and is
benign, and, therefore, very attractive as a catalyst. Zhong et al.
investigated a calcium-based system for the ROP of e-CL

(ESIw Table 1.2, entries 12a12c).43 The molecular weight
distribution was found to be wide (PDI up to 4) but in the
presence of an alcohol, the polymerisation becomes controlled
(PDI close to 1) and rst order in the monomer. The mechanism
of the reaction involves a rupture of the acyloxygen bond of
the monomer and the insertion into the CaO bond of the
calcium alkoxide (Scheme 11).
Piao and co-workers44,45 used calcium ammoniate
(ESIw Table 1.2, entry 1315). The rst step of the mechanism
is the reaction of the catalyst with a hydroxyl- or epoxyterminated initiator to form the active species. The reaction
follows a coordinationinsertion mechanism into the CaO bond,
as proven by the chain end groups (for instance, for entries 14
and 15, one hydroxyl group and one ester). The proposed
Scheme 11 ROP of e-CL using bis(tetrahydrofuran)calcium bis[bis(trimethylsilyl)amide]alcohol system, adapted from Zhong et al.43
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Scheme 12 Mechanism for the ROP of e-CL catalysed by calcium ammoniate.44
mechanism for the following steps is shown in Scheme 12.

Termination is achieved through the addition of an acid.
Tang et al.46 studied strontium-based systems: strontium
ammoniate isopropoxide (ESIw Table 1.2, entry 17), and
strontium di-isopropoxide (ESIw Table 1.2, entry 18). Both
systems led to high molecular weight polymers with a high
polydispersity, but the isopropoxideamine complex resulted
in a signicantly broader molecular weight distribution (PDI
up to 7.4 versus up to 3.3). The high PDI indicates considerable
transesterication. The reaction mechanism is the same as for
the calcium ammoniate catalysed reaction (Scheme 12), with
strontium instead of calcium, and R = iPr.
3. Poor metal-based catalysts. Most of the metal-based
compounds used to catalyse the ROP of e-CL belong to the poor
metals group, most commonly aluminium- or tin-based catalysts.
a Aluminium-based catalysts. Aluminium is a less active
catalyst than many other metals for the ROP of lactones but
is widely used because it allows a good control over the
reaction.32 Wang and Kunioka studied dierent metal triates,
including aluminium(III) triate (ESIw Table 1.3, entry 1), for the
ROP of e-CL.47 All polymerisations were carried out under air at
60 1C without stirring. Aluminium(III) triate was found to be the
best performing catalyst (Mn = 18 400 g mol1, PDI = 1.94),
followed by copper(II) triate (Mn = 16 400 g mol1,
PDI = 1.97, ESIw Table 1.3 entry 28). Sodium(I), magnesium(II)
and ytterbium(III) triates did not catalyse the reaction while
lanthanum(III) and samarium(III) triates produced only
oligomers (Mn = 300 g mol1). Dubois et al.48 studied
the ROP of e-CL using a diethylaluminium alkoxide
(ESIw Table 1.3, entry 4), and a triethylaluminiumamine
system (ESIw Table 1.3, entry 5). Using diethylaluminium
alkoxide, a,o-hydroxyl-PCL containing an amide group inside

the chain was obtained. This suggests that not only the
alkoxide but also the amino group initiate the polymerisation
reaction. With the triethylaluminiumamine system, an
a-hydroxy-o-N-n-butylamide PCL is formed. When the amine
and the catalyst are introduced in the same molar ratio, the
solution gels and the GPC chromatogram is bimodal, suggesting
the presence of two dierent active sites. The initiation is
proposed to proceed through the nucleophilic attack of the
amine on the carbonyl group of the monomer (Scheme 13).
The monomer then opens through cleavage of the acyloxygen
bond, with ethane formation. The alkyl aluminium present at
the end of the chain is responsible for the propagation step
through insertion of the monomer into the OAl bond. The
reaction is terminated by acid hydrolysis.
Florjanczyk and co-workers used a methylaluminoxane
trimethylaluminium system to catalyseinitiate the ROP of
e-CL.49 This system did not exhibit control over the polymerisation (PDI E 2) and back-biting reactions occurred,
leading to the formation of macrocycles. The reaction is said
to proceed through the insertion of the monomer into the
AlOAl bond, as shown in Scheme 14.
Duda et al.50 studied the synthesis of PCL using
dierent aluminium alkoxides, namely diethylaluminium
methoxide (ESIw Table 1.3, entry 6), diethylaluminium allyloxide (ESIw Table 1.3, entry 7) and diisobutylaluminium
methoxide (ESIw Table 1.3, entry 8). Each molecule of
R2AlOR 0 initiates one macromolecule, suggesting that only
alkoxy groups, and not alkyl groups are active in ROP. Like
other authors, Duda et al. noticed that the mechanism of
the reaction is pseudo-anionic with a propagation which is
proposed to proceed through the cleavage of the acyloxygen
Scheme 13 Mechanism of the ROP of e-CL initiated by n-butylamine and catalysed by triethylaluminium.48
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Scheme 14 Mechanism of the initiation step of the ROP of e-CL initiated/catalysed by methylaluminoxane, adapted from Flojanczyk et al.49
Scheme 15 Equilibrium between A3 and A4 clusters of aluminium(III)

isopropoxide, adapted from Ropson et al.62,63
Scheme 16 Disaggregation of A3 species in e-CL, adapted from

Dubois et al.63
bond of the monomer. Moreover, bulkier alkyl substituents on

the aluminium centre led to a more ecient polymerisation.
One of the most studied aluminium-based catalysts is
aluminium(III) isopropoxide (ESIw Table 1.3, entry 9).33,37,5160
It is known that in some solvents, aluminium isopropoxide
molecules do not exist as single molecules but as trimers
(A3) or tetramers (A4), which do not have the same
reactivity.5254,58,59,61,62 An equilibrium exists between the
two species (Scheme 15), with the tetramer being more stable
than the trimer. Dissolved in e-CL, the A3 species disaggregate,
leading to a single species A1 (Scheme 16), which then form a
six-coordinated aluminium complex, [Al(OiPr)33e-CL],58,61,62
the actual catalystinitiator for ROP of e-CL.61 When commercial aluminium(III) isopropoxide is freshly distilled, it is
mainly composed of A3 species while A4 forms with time.61
The polymerisation rate of e-CL using the A1 species is far
higher than the interconversion rate between A3 and A4. As a
consequence, A3 leads to faster and more controlled polymerisations than A4.53
At complete conversion, the coordination number of
the aluminium centres has been proved to be either 4 or 6,
meaning that there is coordination between the ester groups of
the PCL and the aluminium centre (Scheme 17).53,58
Duda studied the eect of the presence of dierent alcohols
(poly(ethylene glycol), 1,5-pentanediol, propan-2-ol, ethanol).52
Alcohols act not only as a chain-transfer agent, but also
inhibit the polymerisation catalysed by aluminium isopropoxide in its A3 form while they accelerate the polymerisation
catalysed by aluminium isopropoxide in its A4 form. As a
result, in the presence of alcohol, the polymerisation rate stays
the same, irrespective of the A3 : A4 ratio. The Al(OiPr)3
catalysed ROP of e-CL has also been shown to be more
controlled at lower temperature (0 to 25 1C in comparison
to B100 1C).64 A comparison of aluminium isopropoxide with
other metal alkoxides by Kricheldorf et al. showed activity
for all alkoxides (ESIw Table 1.3, entry 9a).55 However,
aluminium isopropoxide was found not to induce degradation
of the polymer by intramolecular transesterication or backbiting, unlike other metal alkoxides. Aluminium isopropoxidecatalysed ROP of e-CL in scCO2 (ESIw Table 1.3, entry 8a)
was found to result in a large polydispersity (PDI = 2.34.3),
irrespective of the reaction conditions.37,51 This is believed to
be due to the formation of a large number of dierent species
with dierent reactivities when the aluminium alkoxide is
treated with CO2. In particular, alkoxide groups react with
carbon dioxide to give carbonates.51
Scheme 17 Coordination between the ester groups of the polymer and the aluminium centre after complete conversion of the monomer, adapted
from Duda and Penczek.53
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Dierent methylaluminium diphenolatealcohol systems

(ESIw Table 1.3, entries 1719) resulted in PCL with controlled
molecular weight and low polydispersity indices.65 The
presence of an alcohol to initiate the reaction was necessary
as no polymerisation occurred with only methylaluminium
diphenolate (cf. ESIw). The actual initiating species is
an aluminium alcoholate formed by exchange between the
alcohol and one of the phenyl groups attached to the metal.
Bhaw-Luximon et al. polymerised e-CL in dichloromethane
using an aluminium Schi base complex: HAPENAlOiPr
(ESIw Table 1.3, entry 21), and in toluene using aluminium
isopropoxide (ESIw Table 1.3, entry 9a).33 The polymerisation
was complete after a few hours at 25 1C and a medium
molecular weight polymer was obtained (Mn = 5700 g mol1).
The polymerisation occurs through a coordinationinsertion
mechanism. Taden et al. polymerised e-CL using dierent
aluminium Schi bases based on Salen (ESIw Table 1.3, entries
28 and 29) and Salcen (ESIw Table 1.3, entries 30 and 31)
ligands.66 Only limited information is given on the polymerisation conditions and on the resulting polymers.
However, it is said that the alkyl complexes oligomerise
e-CL while the chloro complexes (cf. ESIw) fail to initiate
ROP. Arbaoui et al. also used dierent aluminium Schi bases
(ESIw Table 1.3, entries 2227).67 These complexes exhibited a
good control of the reaction at low temperature (25 and
40 1C). At higher temperatures, however, control was lost.
At low catalyst concentration, not only one, but both of the
Alalkyl bonds participated in the polymerisation process.
Dierent Al complexes based on salicylaldimines (ESIw
Table 1.3, entries 3235) with dierent substituents on the
imino group, showed an increasing activity in the substituent
order C6F5 44 2,6-iPrC6H3 44 tert-butyl 4 adamantyl.68
The eect of dierent substituents on the two phenyl rings of
the ligand (e.g. Me, iPr, Ph, F, Cl, tBu) of salicylaldiminebased aluminium Schi bases (ESIw Table 1.3, entries 4257)
has also been reported.69 A bulky substituent on the imine
moiety enhanced the polymerisation while bulky substituents
on the salicylidene moiety seem to slow it down. In particular,
among the dierent Schi bases tested, the most ecient one
contained a 2,4,6-tri-tert-butylphenylimine moiety and a
methyl substituent on the 3-position of the salicylidene moiety,
which led to complete conversion of the monomer in a few
minutes (entry 53). Increasing the temperature was found
to speed up the reaction, but also slightly broadened the
molecular weight distribution. Moreover, when the reaction
is carried out in concentrated conditions, the polymerisation
rate is even more important.
Yao et al. used dierent aluminium Schi bases based on
anilido-imine (ESIw Table 1.3, entries 3641).70 The reactivity
decreased with increasing size of the substituents on the
two phenyl rings. It was postulated that it is easier for
the monomer to coordinate to the aluminium centre when
the ligand is less bulky. All tested complexes showed a high
catalytic activity when benzyl alcohol was used to initiate
the reaction, while no polymerisation occurred without
alcohol. In the rst step of the reaction, the alcohol reacts
with the alkyl aluminium to form the active species. A
molecule of monomer will then coordinate to the metal centre.
The ring cleaves at the acyloxygen bond and is inserted into
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Scheme 18 ROP of e-CL using TPP aluminium alkoxidealcohol

systems.71
the AlO bond of the active species. The alcohol does not only
act as an initiator, but also as a transfer agent. Thus, a
polymeric chain can be de-activated or re-activated easily
throughout the polymerisation process.
Dierent (5,10,15,20-tetraphenylporphinato) (TPP) aluminium
alkoxidealcohol systems (ESIw Table 1.3, entries 5860) resulted
in PCL with dierent end groups depending on the system used.71
The polymerisation time is long: 220 h to 24 days for complete
conversion but occurs at relatively low temperature (room
temperature to 50 1C) and leads to a narrow molecular weight
distribution (around 1.1). The polymer chains appear to grow not
only from the TPP aluminium alkoxide introduced in the
medium, but also from the TPP aluminium alkoxide obtained
from the exchange between the starting TPP aluminium alkoxide
and the alcohol introduced in the medium (Scheme 18).
The exchange reactions are much faster than the propagation
reactions, leading to a narrow polydispersity.
Ko, Lin and co-workers investigated the polymerisation of
e-CL using various aluminium complexes (ESIw Table 1.3,
entries 6167).7274 Using 2,2 0 -ethylidenebis(4,6-di-tert-butylphenol) ([(EDBP)Al(m-OBn)]2 and [(PhCHO)Al(EDBP)(m-OBn)]2, (entries 61 and 62), the resulting polymer has a
high molecular weight (up to 44 000 g mol1) with a narrow
polydispersity (1.04 to 1.15).73 The structures of the
compounds are dimeric. During the initiation process, a molecule
of monomer coordinates to one of the aluminium centres of the
dimeric catalyst to form a pentacoordinated intermediate. Then,
a benzylalkoxy group attacks the lactone (Scheme 19). The
polymerisation is slower with the [(PhCHO)Al(EDBP)(m-OBn)]2 than with [(EDBP)Al(m-OBn)]2, which is believed to
be due to the presence of benzaldehyde that slows down the
coordination of the monomer with the aluminium centre.
A more sterically hindered complex, 2,2 0 -methylenebis(4,6-di(1-methyl-1-phenylethyl)-phenol) ([(MMPEP)Al(m-OBn)]2,
ESIw Table 1.3, entry 67), expected to be more active, resulted
in high molecular weight polymers with narrow polydispersity
bearing a benzyl end chain.74 The initiation occurs through the
insertion of a benzyl alkoxy group from the catalyst to the
monomer, leading to the formation of an aluminium alkoxide
intermediate. Ko, Lin and co-workers then used aluminium
thiolate compounds (entries 6366) to prepare high molecular
weight polymers with a thiolate chain end.72 The catalyst from
entry 63 led to a better controlled polymerisation than the
entry 64 catalyst, but no reason was given. The polymerisation
rates of catalysts in entries 65 and 66 are slower than the
polymerisation rates of catalysts from entries 63 and 64, due to
the single AlS functionality in 65 and 66 and two AlS
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Scheme 19 ROP of e-CL catalysed by [(EDBP)Al(m-OBn)]2.75
linkages in 63 and 64. In addition, the initiation is much slower

using the compounds from entry 66 than for the system in
entry 65, due to steric hindrance of the alkyl groups on the
aluminium. The initiation occurs through the insertion of a
thiolyl group from the catalyst into the monomer, forming an
aluminium alkoxide intermediate which then reacts with the
monomer.
Dagorne et al. synthesised a large number of aminophenolate aluminium-alkyl and -alkoxide compounds
(ESIw Table 1.3, entry 68) and investigated them to initiate/
catalyse the ROP of e-CL.76 With the aluminium alkyl
compounds, the monomer formed a complex but the ring
could not be opened under the applied reaction conditions.
With the aluminium alkoxide compounds, e-CL could be
easily opened, conrming other work.
b Tin-based catalysts. Stannous(II) ethylhexanoate (or tin

octoate), is certainly the catalyst which has been used most
often for the ROP of e-CL (ESIw Table 1.4, entry 1). It is
eective, commercially available, easy to handle and soluble in
the most commonly used organic solvents.77 It must be used
together with a nucleophilic compound (generally an alcohol)
to initiate the reaction if a controlled synthesis of the polymer
is to be obtained. The main drawback of tin octoate is that it
requires high temperature, which encourages intermolecular
and intramolecular esterication and thus broadens the
polydispersity.77
Bhaw-Luximon et al. polymerised e-CL in dioxane and

toluene at 110 1C using a stannous(II) ethylhexanoate
ethanolamine system (Scheme 20, ESIw Table 1.4, entry 1b).33
In dioxane, the conversion reached only 40% after 42 h, resulting
in a low molecular weight polymer. In toluene, the polymerisation
completion was reached after 21 h and a medium molecular
weight polymer was obtained (Mn = 5700 g mol1). The rst
step of the polymerisation occurs through a complexation of
ethanolamine with stannous(II) ethylhexanoate. Both groups
(alcohol and amine) can then initiate the polymerisation of e-CL.
The combination of various initiators with tin(II) octoate was
reported by Yagci and co-workers.7880 Initiators studied are
2-(1H-naphto[1,2-e][1,3]oxazin-2-yl)-ethanol (ESIw Table 1.4,
entry 1c), 3-cyclohexene-1-methanol (ESIw Table 1.4, entry 1d),
2-hydroxy-1,2-(diphenylethanone) (ESIw Table 1.4, entry 1e),
2-hydroxy-2-methyl propan-1-one (ESIw Table 1.4, entry 1f)
and 2-hydroxy-1-[4-(2-hydroxyethoxy)phenyl]-2-methyl propan1-one (ESIw Table 1.4, entry 1g). These initiators were specially
chosen for their ability to initiate other kinds of polymerisation,
such that the resulting functionalised PCLs can be used as
macroinitiators for other polymerisation techniques.
Kowalski et al. described the inuence of reaction
conditions on the rate of polymerisation and were able to
prove that the polymerisation process is living.81,82 Their
observations showed that the concentration of the growing
species remains constant throughout the process, that adding
alcohol (in particular butanol, ESIw Table 1.4, entry 1h)
increases the number of active sites, resulting in a higher
Scheme 20 ROP of e-CL using Sn(Oct)2ethanolamine system according to Bhaw-Luximon et al.33
Scheme 21 Formation of the active species for the ROP of e-CL using tin(II) octoate as a catalyst.81
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Scheme 22 Formation of a dormant chain during the polymerisation of e-CL catalysed by tin octoate.81
polymerisation rate, and that carboxylic acids (in particular

ethyl hexanoic acid) temporarily convert the growing species
into dormant molecules, resulting in a decrease in the
polymerisation rate.
Indeed, the rst step of the polymerisation (Scheme 21)
consists of the production of the active species by reacting the
alcohol with the catalyst. The more alcohol is added, the more
the equilibrium is displaced towards the right and the more
active species are created. With increasing carboxylic acid
concentration, the equilibrium shifts to the left and less active
species are present in the medium. This equilibrium exists
throughout the polymerisation (Scheme 22).
The alcohol plays the role of initiator when it is introduced
in a level up to twice the amount of catalyst. When it is
introduced in excess, it also plays the role of a transfer agent.
When the reaction is carried out without an alcoholterminated initiator (ESIw Table 1.4, entry 1a), impurities
present in the tin(II) octoate catalyst (around 1.8 mol% of
OH groups after two consecutive distillations under high
vacuum) appear to play the role of initiator.81 However,
without the addition of a nucleophilic compound, even if
polymerisation occurs, it is not controlled. Kowalski et al.
also showed, using MALDI-TOF analysis, that several species
were produced during polymerisation with two compounds
preferentially formed (Fig. 2).83,84 To explain the preferential
formation of these two main compounds, they postulated
that the catalyst is rst transformed into an alkoxide in order
to be able to initiate the polymerisation. Subsequently, the
polymeric chain will grow by insertion of the monomer into

the alkoxide bond (Scheme 23). Moreover, the amount of
each fraction present in the medium depends on dierent
parameters, such as the concentration of initiator and the
polymerisation time.84
Tin(II) octoate has also been combined with ureidopyrimidinone-alcohol (UPy) compounds (ESIw Table 1.4, entries
1j and 1k) as initiators.85 The rst alcohol compound, bearing
a methyl group, was not a good initiator due to its poor
solubility in organic solvents. Using the second more soluble
alcohol, bearing a 1-ethylpentyl moiety, the polymerisation
was signicantly more controlled: near complete conversion
was reached and polymers with a medium polydispersity were
obtained (PDI = 1.1 to 1.36). However, it was mentioned that
dimerisation of the initiator occurred, potentially increasing
the measured polydispersity. Indeed, at the reaction temperature
(80 1C), there is a high rate of on/o UPy dimerisation (i.e. two
initiators can easily be associated by quadruple hydrogen
bonding (Scheme 24)). The dimer form does not interact
with the catalyst and formation of the polymeric chains is
postponed until the initiator is present in its monomeric form.
Bratton et al. investigated the polymerisation of e-CL
initiated by butan-1-ol and catalysed by stannous(II)
ethylhexanoate in scCO2 (ESIw Table 1.4, entry 1h).86 It
was found that increasing the pressure of the medium resulted
in a decrease in the polymerisation rate while increasing
the temperature increased the polymerisation rate. The
polymerisation in scCO2 was also compared to the same
Fig. 2 The dierent polymers formed during the ROP of e-CL initiated with butanol and catalysed with tin(II) octoate, the framed compounds are
preferentially formed.83
Scheme 23 Initiation steps of the ROP of e-CL initiated by an alcohol and catalysed by tin(II) octoate according to Kowalski et al.83
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Scheme 24 Dimerisation of the ureidopyrimidinone-alcohol compound.
polymerisation with the same conditions in organic solvents

and in bulk. It was found that the polymerisation rate in
scCO2 was the same as in THF, which was slightly slower
than in toluene and signicantly slower than in bulk.
Primary aminetin(II) octoate systems follow a similar reaction
mechanism as alcoholtin(II) octoate systems. Two polyamino
dendrimers, DAB-Am-8 and DAB-Am-32 (ESIw Table 1.4,
entries 1n1p), used as initiators resulted in high molecular
weight PCL dendrimers.87
Stassin et al. polymerised e-CL using dibutyltin dimethoxide
in scCO2 and compared it to the polymerisation in bulk, in
toluene and in 1,1,2-trichloro-1,2,2-triuoroethane (CFC-113)
(ESIw Table 1.4, entry 3).88,89 The highest polymerisation rate
is obtained in bulk, then in toluene, followed by CFC-113,
while the polymerisation in scCO2 is the slowest.88 They
demonstrated that the alkoxide is carbonated in scCO2,
slowing down the reaction as discussed before.89
The eciency of tin triate (ESIw Table 1.4, entry 6) and
scandium triate (ESIw Table 1.4, entry 1) for the ROP of
e-CL has been compared with tin octoate (ESIw Table 1.4,
entry 1m) and (Bu)2Sn(Oct)2 (ESIw Table 1.4, entry 4).77,90
The living character of the polymerisation is proven by the
linear relationship between molecular weight and conversion.
At 110 1C, the temperature which gives the best results with tin
octoate, the polymers obtained with the triate compounds
showed a similar molecular weight and polydispersity to these
obtained with Sn(Oct)2 and (Bu)2Sn(Oct)2, but with a reduced
reaction time (3 h instead of 24 h). At low temperatures,
triate compounds led to high molecular weight polymers with
narrow polydispersity while there was no conversion of the
monomer with the two other catalysts. The polymerisation
of e-CL by tin triate is proposed to proceed through a
coordinationinsertion mechanism.
4. Transition metal-based catalysts. If we exclude scandium,

yttrium and lanthanum (see section 5. Rare earth metal-based
catalysts), the most commonly used transition metal for the ROP
of lactones is titanium, but recently, zirconium has attracted
some interest.32 In general, the less toxic metals are used
preferentially.
Zinc mono- and di-alkoxides have been reported to be good
initiators for the ROP of e-CL (ESIw Table 1.5, entries 3134),
resulting in a degree of polymerisation (DP) over 100
being obtained with a PDI between 1.05 and 1.1.91 The polymerisation is carried out through a coordinationinsertion
mechanism relying on the cleavage of the acyloxygen bond
of e-CL (Scheme 25).
Sarazin et al. used dierent zinc complexes (ESIw Table 1.5,
entries 36 and 37) and reported them to be more stable and
to show higher activity than their magnesium analogues.92
Both complexes were found to be very good catalysts as the
polymers can be obtained with a high throughput (between 50
and 300 kg (mol metal)1 h1). No indication is given regarding
the molecular weight and polydispersity of the polymer
obtained with the rst complex, but the one obtained
with the second complex presents a high molecular weight
(55 000 g mol1) despite a moderate PDI (2.3).
Zinc oxide successfully catalysed the ROP of e-CL in the
presence of an ionic liquid ([bmim][BF4]) under microwave
treatment (ESIw Table 1.5, entry 29).93 The combination of
these two elements (ionic liquid + microwave) increases the
eciency of the ROP. Polymers with average molecular
weights between 2260 g mol1 and 11 060 g mol1 were
obtained with PDIs between 1.30 and 2.50. The reaction
mechanism of zirconium(IV) acetylacetonate catalysed ROP
of e-CL (ESIw Table 1.5, entry 39) has been elucidated by
Dobrzynski (Scheme 26).94
Scheme 25 ROP of e-CL using zinc mono-alkoxide.91
Scheme 26 ROP of e-CL using Zr(acac)4 according to Dobrzynski.94
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Iron(III) alkoxide complexes (ESIw Table 1.5, entries 26 and 27)

have been found to be ecient catalysts that led to high
molecular weight polymers.95 A narrow molecular weight
distribution was obtained with the di-Fe complex, but a
wider distribution was obtained with the mono-Fe complex.
This is said to be due to a low level of impurities which
deactivate the catalyst. For the polymerisation catalysed by
the di-Fe complex, the reaction is rst order in both the
monomer and the complex. For the mono-Fe complex
catalyst, the polymerisation reaction is rst order in the
monomer and depends on the square root of the complex
concentration.
Davidson et al. reported the use of titanium complexes
based on catechol ligands (ESIw Table 1.5, entries 613).96
All polymers synthesised presented a narrow polydispersity
suggesting controlled polymerisation. Chmura, Davidson and
co-workers investigated the use of titanium(IV) (ESIw Table 1.5,
entries 25) as well as zirconium(IV) (ESIw Table 1.5, entries
4042) complexes with amine bis(phenolate) ligands.97,98 Only
the bulkiest titanium(IV) complex was found to be active.
However, the high polydispersity resulting from signicant
transesterication reactions suggests that the polymerisation
was not controlled. As far as zirconium(IV) complexes were
concerned, the less bulky were more active and exhibited
better control over the polymerisation reaction. Also, minor
dierences in the environment of the metal centre were
found to have a signicant impact on the complex reactivity.
For both studies, polymers bearing isopropoxyl end chains
suggested that the initiation of the polymerisation occurs
via the isopropoxide groups of the complexes. Titanium(IV)
complexes with bisphenolate ligands (ESIw Table 1.5,
entry 15 and Table 2.4, entry 6) have been reported by
Takeuchi et al.99 The Lewis acidity of the catalyst
should not be too high for the polymerisation to occur.
Moreover, when polymerisation does occur, two polymer
molecules are formed for each molecule of catalyst present
(Scheme 27).
Mahha et al.100 investigated the oligomerisation of e-CL
using heteropolyacids (ESIw Table 1.5, entries 4648 and 51),
molybdenum(VI) complexes (ESIw Table 1.5, entry 62 and
Table 2.4, entry 19), vanadium(IV) complexes (ESIw Table 1.5,
entry 25) and compared their activity to the activity of
sulfuric (ESIw Table 1.5, entry 16) and phosphoric (ESIw
Table 1.5, entry 17) acids. The reactions catalysed by heteropolyacids were found to work better under dioxygen than
under inert atmosphere. During the polymerisation under
inert atmosphere, V(IV) and Mo(V) species were reduced
and became inactive. Moreover, the polymerisation rate
with heteropolyacids was higher than with sulfuric and
phosphoric acids.
5. Rare earth metal-based catalysts. Rare earth metalbased compounds are good catalysts due to their moderate
acidity.32 Moreover, these compounds do not have any known
toxicity.38 Scandium triates (ESIw Table 1.6, entries 1a, 1c
and 1d) were combined with water and benzyl alcohol
(initiators) to catalyse the ROP of e-CL.101 High molecular
weight polymers (Mn up to 25 000 g mol1) with low polydispersity index (PDI o 1.18) were obtained. Moller et al.
conrmed these results using ethanol, butan-2-ol and phenylethan-1-ol as initiators (ESIw Table 1.6, entries 1e1g).77 Other
rare earth metal triates, namely yttrium(III) (ESIw Table 1.6,
entry 3), lanthanum(III) (ESIw Table 1.6, entry 14), caesium(IV)
(ESIw Table 1.6, entry 17), neodymium(III) (ESIw Table 1.6,
entry 20), europium(III) (ESIw Table 1.6, entry 35), gadolinium(III)
(ESIw Table 1.6, entry 36), ytterbium(III) (ESIw Table 1.6,
entry 37) and lutetium(III) (ESIw Table 1.6, entry 39) triates
where studied later using benzyl alcohol as initiator in both
organic solvents and ionic liquids.102 Scandium triate was
the most ecient in toluene at 25 1C (Mn = 3500 g mol1,
PDI = 1.13, total conversion in 2 h with [e-CL] : [Sc(OTf)3] :
[BnOH] = 50 : 1 : 1), slightly better than lanthanum triate
(Mn = 2900 g mol1, PDI = 1.16, complete conversion in 3 h,
same conditions). Various new initiators were also used. In
particular p-xylene glycol gave a polymeric chain which grew
from both hydroxyl groups, leading to two polymer chains
linked by p-xylene glycol. The signal obtained from GPC was
bimodal, probably due to the presence of water (from
the catalyst) which initiated other chains, leading to an
a-(carboxylic acid)-o-hydroxyl PCL. For the polymerisations
in ionic liquids, no initiator was added, but some water is
coordinated to the metal triates. Three dierent ionic liquids
were tested: [bmim][BF4], [bmim][PF6] and [bmim][SbF6].
In [bmim][BF4], scandium and europium triates did not
polymerise caprolactones and other rare earth triates only
led to oligomers (maximum Mn = 600 g mol1), while several
days were necessary to achieve a conversion of only 30%.
In [bmim][PF6], most of the polymerisation reactions were
complete after ca. 2 days and the resulting polymers had a
molecular weight of around 3000 g mol1. Lanthanum,
caesium, gadolinium and lutetium triates led to longer
polymers (up to 4400 g mol1 for Lu(OTf)3). However,
the polymerisation did not appear to be controlled fully as
suggested by the polydispersity (PDI between 1.41 and 1.56).
In [bmim][SbF6], the molecular weights were lower than the
values obtained in [bmim][PF6], but polydispersities were
narrower. Moreover, when scandium, europium, gadolinium
and lutetium were used, it was impossible to separate the
polymer from the ionic liquid. The Ce(OTf)4 in [bmim][SbF6]
system was tested as a recyclable system for the ROP of
e-CL: it was possible to re-use it 3 times without any change
Scheme 27 Formation of 2 polymeric chains for 1 molecule of catalyst during the ROP of e-CL using a titanium(IV) complex.99
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Scheme 28 Monomer-activated cationic mechanism for the ROP of e-CL initiated by scandium triate.
in molecular weight and polydispersity of the polymer. The

mechanism of the reaction is cationic and monomer activated
(Scheme 28): rst the monomer is coordinated to the catalyst to
form a complex, which is then attacked by the alcohol, thereby
freeing a proton that subsequently opens the ring to produce the
linear ester. The linear ester, playing the role of the alcohol,
repeats the same steps, leading to the polymer chain.
Deng and co-workers studied the ROP of e-CL catalysed
by yttrium(III) isopropoxide (ESIw Table 1.6, entry 4a) and
bimetallic isopropoxides containing yttrium (ESIw Table 1.6,
entries 57).103 Y(OiPr)3 (entry 4a) and Sn[Y(OiPr)4]2 (entry 7)
were revealed to be more ecient catalysts than Y[Al(OiPr)4]3
(entry 5) and Y[Sn(OiPr)3]3 (entry 6). In the two rst
compounds, yttrium, the more active catalysing metal (YO
bonds have a greater activity than SnO or AlO bonds), is
located towards the outside of the complex. The mechanism of
the reaction is said to be the same as for other alkoxides.
However, according to other authors, the mechanism of the
reaction with yttrium(III) isopropoxide is not as simple and it is
still unknown because the catalytically active compound is
actually a cluster of ve yttrium atoms attached to a single
central oxygen atom.104,105
Rare earth metal phenyl compounds, namely triphenyl
yttrium (ESIw Table 1.6, entry 9), triphenyl neodymium (ESIw
Table 1.6, entry 19) and triphenyl samarium (ESIw Table 1.6,
entry 22) have been investigated for both bulk and solution
polymerisation (in toluene, THF, benzene and 1,4-dioxane).35
A higher molecular weight and yield were obtained for
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Scheme 29 ROP of e-CL using rare earth phenyl compounds according

to Deng et al.35
polymerisation in bulk, while only oligomers were obtained

when it was conducted in THF or 1,4-dioxane. These systems
were found to be more ecient than phenyl lithium. However,
rare earth metal phenyl compounds not only catalyse the
polymerisation of PCL but also its decomposition. Consequently,
the polymerisation reaction needs to be stopped early enough
to prevent the decomposition of the formed polymer. It was
suggested that neither the acyloxygen bond nor the alkyl
oxygen bond is cleaved during the initiation. Instead, the
polymerisation is said to follow a coordinationdeprotonation
insertion process (Scheme 29), followed by an intramolecular
transesterication in the later stage when decomposition of the
polymer starts.
Agarwal et al. used tris(bis-trimethylsilyl)amido samarium
(ESIw Table 1.6, entry 24) and samarium trihalide complexes
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Scheme 30 ROP of e-CL using Sm(III) m-bromo-bis(trimethylsilyl)amido complexes according to Agarwal et al.106
Scheme 31 ROP of e-CL with yttrium isopropoxide grafted onto silica surfaces.56
(ESIw Table 1.6, entries 25 and 26).106 These compounds were

found to be good catalysts for room temperature ROP
of e-CL. They give high molecular weight polymers
(Mn 4 10 000 g mol1) over a short period of time (only a
few minutes) with a high monomer conversion (498%). The
reaction is also found to be more ecient at low temperature
(10 1C) than at room temperature. However, these catalysts
give rise to a relatively high polydispersity index of the nal
polymer (B2.0). The rst reaction step is likely to be the
decoordination of THF in exchange for an e-CL molecule.
Several kinds of initiating species are then produced
(Scheme 30).
Yttrium isopropoxide grafted onto silica surfaces (ESIw
Table 1.6, entry 8) was used in toluene at 40 1C in the presence
of 2-propanol.56 This heterogeneous system led to moderate
molecular weight polymers (Mn B 1900 g mol1) in a short
time (B1 h). However, some silica particles can easily remain
attached to the polymeric chains if no particular care is taken
when detaching the polymeric chains from the support. After
treatment with a termination agent (aqueous hydrochloric
acid solution or alcohol), the silica particles must be allowed
to settle down for several hours before the supernatant can be
analysed. The propagation of the polymerisation mechanism is
based on a fast alkoxidealcohol exchange leading to a
low polydispersity index (Scheme 31). The catalyst is easily
regenerated if the termination agent is 2-propanol.
Lin et al. polymerised e-CL using a lanthanum complex
based on a Schi base ligand (ESIw Table 1.6, entry 16) and
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obtained high molecular weight polymers with a unimodal

molecular weight distribution.107 Only one species was found
to be active and the polymerisation was said to proceed
through acyloxygen bond cleavage.
Samarium(II) aryloxide complexes (ESIw Table 1.6, entries
27 and 28) resulted in high molecular weight polymers with a
narrow polydispersity within a few minutes and at room
temperature.108 At the early stage of the polymerisation, a
colour change from dark brown to pale yellow proved that
Sm(II) was immediately oxidised to Sm(III), suggesting that
Sm(III) actually catalyses the reaction. The termination step
involved the addition of an alcohol, which forms an alkoxide
at the end of the polymeric chain (Scheme 32). However,
because of paramagnetism of samarium species, no information
is available on the structure of the growing species before
termination. As a consequence, the mechanism of the reaction
is still unknown.
Various organolanthanide complexes have also been studied
as catalysts: SmMe(C5Me5)2(THF) (ESIw Table 1.6, entry 29),
Scheme 32 Formation of an alkoxide at the end of the polymeric

chain when an alcohol is used to terminate the polymerisation.108
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Scheme 33 Reaction of e-CL with [SmH(C5Me5)2]2, followed by hydrolysis.109
Scheme 34 Reaction of e-CL with SmMe(C5Me5)2(THF), followed by hydrolysis.109
Scheme 35 Reaction of e-CL with SmOEt(C5Me5)2(Et2O), followed by reaction with acetic anhydride.109
[SmH(C5Me5)2]2 (ESIw Table 1.6, entry 30), [YbMe(C5H5)2]2

(ESIw Table 1.6, entry 38), SmOEt(C5Me5)2(Et2O) (ESIw
Table 1.6, entry 31), [YOMe(C5H5)2]2 (ESIw Table 1.6, entry 10)
and YOMe(C5Me5)2(THF) (ESIw Table 1.6, entry 11).109
The polymerisation gave high molecular weight polymers
(Mn up to 140 000 g mol1) with a narrow polydispersity
(1.05 to 1.19). The mechanism of the reaction was determined
to be dierent for each catalyst. The reaction of
[SmH(C5Me5)2]2 with e-CL produced 1,6-hexanediol after
hydrolysis, indicating a reduction of the carbonyl group of
the monomer (Scheme 33).
The reaction of SmMe(C5Me5)2(THF) with e-CL produced
7-hydroxy-2-heptanone after hydrolysis, indicating a scission
of the acyl bond followed by an alkyl addition (Scheme 34).
The reaction of SmOEt(C5Me5)2(Et2O) with e-CL produced
5-(ethoxycarbonyl)pentyl acetate after hydrolysis. The structure
obtained was the same as Endo et al.71 obtained when using
(5,10,15,20-TPP) aluminium ethyl, indicating that a similar
mechanism occurred here (Scheme 35).
The reaction of YOMe(C5Me5)2(THF) with e-CL does not

occur if the two compounds are introduced in stoichiometric
quantities, resulting in the recovery of the monomer upon
hydrolysis. For the reaction to occur, twice the amount of
monomer must be used. In this case, an ester alcohol is
produced and 1 equivalent of monomer remains unreacted
(Scheme 36).
Martin et al.110,111 reported on the polymerisation of e-CL
using [tris(hexamethyldisilyl)amide]yttrium in the presence of
2-propanol (ESIw Table 1.6, entry 12b). The alcohol was
required to control the polymerisation (PDI = 3.21 without
alcohol, ESIw Table 1.6, entry 12a). When used in the presence
of alcohol, the polymerisation using the yttrium amide was
well controlled up to an alcohol : yttrium ratio of 50 : 1. The
polymerisation progresses through the coordinationinsertion
mechanism generally accepted for aluminium33,55 and yttrium103
alkoxides. First, yttrium alkoxide is formed by replacement of
the amide with the alcohol (Scheme 37). Propagation occurs
through insertion of the monomer into the YO bond by
Scheme 36 Reaction of e-CL with YOMet(C5Me5)2(THF) for dierent e-CL : catalyst ratios.109
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Scheme 37 Formation of the active species in the ROP of e-CL with yttrium amide and propan-2-ol.110,111
cleavage of the acyl bond of the monomer. The polymerisation

is stopped by the addition of an excess of acid. This produces
a polymeric chain with one hydroxyl chain end and one
isopropoxy ester chain end.
Using alcohols other than 2-propanol, namely methanol,
n-butanol, 1-phenyl-propan-2-ol, 2-(3-thienyl)ethanol and
N-pyrrol-2-ethanol, as initiator results in varying chain ends.
All gave rise to polymers with a controlled molecular weight
and a low polydispersity index.
An yttrium tris(2,6-di-tert-butylphenolate)2-propanol system
(ESIw Table 1.6, entry 13) was used to produce PCL with a
controlled molecular weight and narrow polydispersity.104,112
The alcohol reacts with the catalyst to form yttrium isopropoxide. The reaction is thus virtually reduced to an yttrium
isopropoxide catalysed reaction. Indeed, the use of a small
alcohol as initiator is necessary as the catalyst alkoxides are
too big to allow a direct reaction.
Mingotaud et al. used yttrium and lanthanum isopropoxides to catalyse the ROP of e-CL in bulk, in toluene
and in scCO2 (ESIw Table 1.6, entry 15).37 In bulk, the
polymerisation was not controlled at all (PDI = 6.28),
certainly because the catalyst is insoluble in the monomer,
giving rise to a heterogeneous system. In toluene and in scCO2,
the results are similar for yttrium isopropoxide, but the

reaction is much slower in scCO2 than in toluene for
lanthanum isopropoxide. By varying temperature and
pressure in scCO2, the best results were obtained at 110 1C
at a pressure of 200 bar.51
Metal-based compounds are certainly the most widely
studied class of catalysts for ROP of e-CL. However, enzymes
and organic compounds are gaining in importance and are
discussed in the following sections.
Enzymatic ring-opening polymerisation (eROP)
A mechanism for eROP using lipases has been proposed by
several authors (Scheme 38): rst, the lipase reacts with
the monomer to form a lipase-activated CL complex, then the
alcohol reacts with the complex.113116 Modelling studies on the
eROP of e-CL have revealed that polymerisation, degradation
and enzyme deactivation all occur simultaneously.117
Dong et al. showed that the water content in the reaction
medium is extremely important and must be neither too high,
nor too low to have polymers with a high molecular weight
and a narrow polydispersity using the lipase PSL (from
Pseudomonas sp.).118 Also, they found that adding molecular
sieves into the medium resulted in good control of the water
Scheme 38 Mechanism of the eROP.113116
Scheme 39 Mechanism of the eROP proposed by Dong et al.118
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content, and consequently the polymerisation. A new mechanism

for the polymerisation of e-CL using PSL was subsequently
proposed: ring-opening occurs in the early stage of the polymerisation, and linear condensation in the later stage
(Scheme 39). This mechanism is consistent with the sharp
decrease in the amount of water at the early stage of the
polymerisation and its increase at the later stage. The pH was
also found to be important (optimal at 7.2 for PSL).119 Indeed,
the pH aects the ionisation of the amino acid residues at the
active site of the lipase, which inuences its ability to bind to
substrates.
Kobayashi and coworkers113,114,120125 have produced a
vast array of work on enzymatic catalysis of ROP of lactones
and in particular e-CL. They tested a wide number of enzymes
from dierent origins: porcine pancreas (PPL, ESIw Table 1.7,
entry 1), Aspergillus niger (lipase A, ESIw Table 1.7, entry 2),
Candida cylindracea (now called Cylindracea rugosa, lipases B
and CC, ESIw Table 1.7, entries 3 and 4), C. antarctica (lipase
CA, ESIw Table 1.7, entry 7), Pseudomonas aeroginosa (lipase
PA, ESIw Table 1.7, entry 8), Pseudomonas cepacia (now
called Burkholderia cepacia126 lipase PS-30, ESIw Table 1.7,
entry 9), Pseudomonas uorescens (lipases P and PF, ESIw
Table 1.7, entries 10 and 11), Rhyzopus delemer (lipase RD,
ESIw Table 1.7, entry 14), Rhizopus japonicus (lipase RJ,
ESIw Table 1.7, entry 15) and hog liver esterase (HLE, ESIw
Table 1.7, entry 19).
A large number of dierent solvents were tested (1,4-dioxane,
acetonitrile, acetone, 2-butanone, tert-butyl alcohol, tert-butyl
methyl ether, isopropyl ether, benzene, carbon tetrachloride,
heptane, cyclooctane, and isooctane) and it appeared that the
eciency of the polymerisation was linked to the hydrophobicity of the solvent used: when eROP was conducted in
hydrophilic solvents, the conversion was very low after 10 days
and the resulting polymers had a low molecular weight. It was
found that hydrocarbons are more suitable solvents for
eROP, while bulk reactions are still faster than reactions
in solution.123 The lipase CA was the most ecient: high
conversion was obtained in less than 24 h while more than
10 days were needed for the other lipases. In addition, a
smaller amount of enzyme was added to the reaction medium
(120 mg vs. 50 mg for 1 mmol of monomer). This is because
this particular lipase (Novozyms 435) was immobilised while
all the other lipases tested were used as a free powder. Kumar
and Gross conrmed many of their conclusions concerning the
use of hydrophilic or hydrophobic solvents for the Novozyms
435 lipase.127 They also showed that performing the reaction
on a larger scale increased the molecular weight of the polymer: it is believed to be due to the susceptibility to take up
water during the reaction. Moreover, at higher dilution, the
PDI was found to be lower. A study on the inuence of both
enzyme water content and polymerisation temperature on the
eROP of e-CL catalysed by Novozyms 435 showed that the
polymerisation temperature had little inuence on the polymerisation.128 It was also noticed that a decrease in enzyme
water content increased the number of polymeric chains and
the average molecular weight of the polymer, consistent with
the fact that water is the actual initiator of the polymerisation.
Uyama et al. used lipase from C. antarctica (CA, ESIw
Table 1.7, entry 7a) and showed that the presence of an
3500 | Chem. Soc. Rev., 2009, 38, 34843504
initiator leads to a faster polymerisation reaction (78% of

conversion when [1-octanol]0/[e-CL]0 = 0.2 after 1 h of
reaction instead of 46% without alcohol).122 However, alcohol
addition led to shorter polymeric chains (Mn = 1000 g mol1
instead of 5200 g mol1 with a conversion around 75%) with a
narrower distribution (PDI = 1.5 instead of 3.2), showing that
the presence of alcohol provides control over the polymerisation
reaction. Studies with Lipase B from C. antarctica (CALB,
Novozyms 435) and a lipase from P. cepacia (PC) showed
that the polymerisation is faster in bulk than in organic solvent
and shifted towards the formation of linear polymers, while
the reaction in acetonitrile, THF or dioxane tended towards
the formation of cyclic oligomers.129,130 Cyclic oligomer
formation is also enhanced in a more dilute system. For the
lipase from PC, the products are essentially linear, even in
solution.130 When CALB was used as a catalyst, the initial step
of the polymerisation involved nucleophilic attack of serine
105 of the lipase on the monomer.129,130 When a-D-glucopyranoside and b-D-glucopyranoside were used as initiators,
CALB acylated the primary alcohol.130 Polymerisation of
e-CL with lipase from C. antarctica in scCO2 resulted in
polymers similar to those generally obtained with enzymes
in organic solvents, but with a narrower polydispersity.131
Hedfors et al. synthesised PCL terminated with thiol
functional groups using Novozyms 435 as a catalyst.132 This
was possible because this catalyst is chemoselective. Three
dierent methods were employed:
- the ROP was initiated by a compound with both alcohol
and thiol groups; the hydroxyl group initiated the reaction
while the thiol group remained unreacted;
- the ROP was initiated by the water present in commercial,
undried e-CL and was terminated by the addition of a
thiolactone: the lipase opens the thiolactone ring, the same
way it opens the lactone ring;
- the ROP was initiated by the water present in commercial,
undried e-CL and was terminated by the addition of a
compound bearing both carboxylic acid and thiol groups: a
transesterication reaction between the polymer and the
carboxylic acid group of the terminator gives the thiol-terminated
polymer.
The use of such chemoselective catalyst compounds for the
ROP of e-CL allows for a choice of the terminal groups on the
polymer without the need for any protecting and deprotecting
steps, a major advantage.
Porcine pancreatic lipase was tested under dierent conditions
by MacDonald et al. (ESIw Table 1.7, entries 1a and 1b).115
Dierent solvents (1,4-dioxane, toluene and heptane) were
tested and the best results were found for bulk reaction or
for reactions in heptane. The optimal temperature was 65 1C
for a reaction time of 96 h. Crude porcine pancreatic lipase
(PPL, ESIw Table 1.7, entry 1c) and P. cepacia lipase (PS-30,
ESIw Table 1.7, entry 9a) were investigated for bulk polymerisation of e-CL and resulted in crystalline polymers composed
of 12 to 25 units in 1100 h and 240 h, respectively.116 The
molecular weight distribution was not reported.
Ethyl glucopyranoside (EGP) was used as the initiator with
various enzymes, namely Candida rugosa (ESIw Table 1.7,
entry 4b), C. Antarctica (ESIw Table 1.7, entry 7g), P. uorescens
(ESIw Table 1.7, entry 12), P. cepacia (ESIw Table 1.7,
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entry 9d), Mucor miehei (ESIw Table 1.7, entry 17), Mucor
javaniocus (ESIw Table 1.7, entry 18) and porcine pancreas
(ESIw Table 1.7, entry 1e) lipases.133 Only CA and PPL led to
signicant monomer conversion. The structure of the resulting
polymer showed that the reaction was selective and that only
the primary alcohol was reactive. Surprisingly, under the same
conditions, methyl glucopyranoside (MGP) could not initiate
the reaction (cf. ESIw).

ROP catalysed by organic compounds and inorganic acids

Pratt and co-workers134,135 used aza-compounds, namely
1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD, ESIw Table 1.8,
entry 1), N-methyl-1,5,7-triazabicyclo[4.4.0]dec-1-ene (MTBD,
ESIw Table 1.8, entry 2) and 1,8-diazabicyclo[5.4.0]-undec-7-ene
(DBU, ESIw Table 1.8, entry 3) as catalysts for the ROP of
e-CL. MTBU and DBU required co-catalysis by thiourea.
Indeed, thanks to its bifunctionality, TBD has the ability to
simultaneously activate both the alcohol and the monomer
(Scheme 40), while MTBD and DBU can only activate the
alcohol. The thiourea is needed to activate the monomer
(Scheme 41). The reaction is terminated by the addition of
benzyl alcohol: benzyl acetate is formed and the catalyst is
regenerated.
Phosphazene bases have been used to catalyse the polymerisation of e-CL, which was found to be well controlled
(predictable molecular weight, narrow PDI) but very slow
(only 14% conversion after 10 days at 80 1C).137 The proposed
mechanism is given in Scheme 42.
A study of various carboxylic acids (lactic acid, tartaric acid,

hexanoic acid, propionic acid, citric acid, 6-hydroxyhexanoic
acid, ESIw Table 1.8, entries 49) and amino acids (glycine,
proline and serine, ESIw Table 1.8, entries 1012) in the
presence of benzyl alcohol to initiate the reaction have been
reported by Persson and co-workers.138,139 Organic acids with
pKa values between 3 and 5 were found to be able to catalyse
the ROP of e-CL, giving polymers with a weight average
molecular weight of up to 2800 g mol1 and a polydispersity
between 1.2 and 1.3. The order of catalytic eciency is said to
be tartaric acid 4 citric acid 4 lactic acid 4 proline. The
other catalysts led to only a low conversion after 24 h
(o12%). The catalysts were recovered after precipitation of
the polymer in cold methanol, followed by ltration and
evaporation of the solvent under reduced pressure. The reaction
system could be reused up to two times without a decrease in
the molecular weight of the polymer. The ROP of e-CL with
these carboxylic acids and amino acids does not require
addition of an alcohol. In this case, the reaction is initiated
by an hydroxyl group or amine group present on the catalyst.
The polymerisation is proposed to proceed through a monomer
activation mechanism. In the initiation step, the nucleophile
(alcohol or amine) reacts with the proton-activated monomer.
The propagation occurs similarly, with the nucleophile being
the alcohol or amine-terminated chain.
Shibasaki et al. investigated the polymerisation of e-CL
catalysed by hydrochloric acid (in solution in diethyl ether)
and initiated with n-butanol.140 This is an inexpensive way to
produce polymers with narrow polydispersity. Methanesulfonic
Scheme 40 ROP of e-CL through dual activation using TBD, adapted from Chuma et al.136
Scheme 41 ROP of e-CL through dual activation using DBU and thiourea.134
Scheme 42 Mechanism for the ROP of e-CL using BEMP as catalyst.137
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Scheme 43 Competition between the activation of the monomer and

the deactivation of the alcohol during the ROP of e-CL catalysed by
HOTf.
acid (MSA) and triuoromethanesulfonic acid (HOTf) were

compared with hydrochloric acid by Gazeau-Bureau et al.141
The ROP reaction is faster in toluene than in chlorinated
solvents. MSA was revealed to be as active as HOTf. The
activity of triuoromethansulfonic acid is said to be optimal
for a catalyst : initiator ratio of 1 : 1 while the activity of MSA
increases with an increasing amount of catalyst, allowing a
faster reaction without a decrease in control. This is said to be
due to the competition between the activation of the monomer
and the deactivation of the alcohol (Scheme 43). Indeed, an
excess amount of HOTf would increase the deactivation of the
alcohol resulting in a slower polymerisation while an excess of
MSA would increase the activation of the monomer, resulting
in a faster polymerisation.
Conclusion
The main route to obtain high molecular weight PCL is
the ROP of e-CL. A large number of compounds, either
metal-based, organic or even enzymatic systems can catalyse
the ROP of e-CL, as shown by the vast amount of published
work. Even some inorganic acids have been used successfully.
At present, metal-based compounds have been studied the
most, but enzymatic and organic compounds as well as
inorganic acids are gaining in prominence. Some catalysts
need specic conditions to catalyse the ROP of e-CL, while
several can be used in mild conditions. The termination step
usually requires the addition of an acid or of an alcohol, but
the polymer can also remain alive. The catalyst is mainly
chosen for the particular application, and the desired reaction
conditions.
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Synthesis of Polycaprolactone

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View Online / Journal Homepage / Table of Contents for this issue

www.rsc.org/csr | Chemical Society Reviews

Synthesis of polycaprolactone: a revieww

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Received 15th January 2009

Driving Innovation in Chemistry and Chemical Engineering,

Marianne Labet was born in

3484 | Chem. Soc. Rev., 2009, 38, 34843504

bre axis.2 The physical, thermal and mechanical properties of

Wim Thielemans obtained a

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Number average molecular weight

PCL has uses in dierent elds such as scaolds in tissue

Preparation of the monomers

Fig. 1 Cleavage of the polymeric chains during the degradation of PCL.

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molecular weight and a lower polydispersity. As a consequence,

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There are two methods to prepare PCL: the condensation of

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Scheme 7 Intermolecular transesterication reaction during the polymerisation of PCL.

Scheme 8 Intramolecular transesterication reaction during the polymerisation of PCL.

catalyst and the insertion of the monomer into a metaloxygen

Catalysts used for ROP and reaction conditions

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consequence, polymerisation is not well controlled due to

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ROP of e-CL catalysed by LDA.34

Scheme 10 ROP of e-CL catalysed by cyclopentadienyl sodium.36

medium polydispersity (PDI = 1.06 to 1.35).40 The complex

investigated a calcium-based system for the ROP of e-CL

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Scheme 12 Mechanism for the ROP of e-CL catalysed by calcium ammoniate.44

mechanism for the following steps is shown in Scheme 12.

alkoxide, a,o-hydroxyl-PCL containing an amide group inside

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Scheme 15 Equilibrium between A3 and A4 clusters of aluminium(III)

Scheme 16 Disaggregation of A3 species in e-CL, adapted from

bond of the monomer. Moreover, bulkier alkyl substituents on

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Dierent methylaluminium diphenolatealcohol systems

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Scheme 18 ROP of e-CL using TPP aluminium alkoxidealcohol

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Scheme 19 ROP of e-CL catalysed by [(EDBP)Al(m-OBn)]2.75

linkages in 63 and 64. In addition, the initiation is much slower

b Tin-based catalysts. Stannous(II) ethylhexanoate (or tin

Bhaw-Luximon et al. polymerised e-CL in dioxane and

Scheme 20 ROP of e-CL using Sn(Oct)2ethanolamine system according to Bhaw-Luximon et al.33

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polymerisation rate, and that carboxylic acids (in particular

polymeric chain will grow by insertion of the monomer into