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

CRITICAL REVIEW

www.rsc.org/csr | Chemical Society Reviews

Synthesis of polycaprolactone: a revieww

Marianne Labet and Wim Thielemans*
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).

Published on 25 September 2009. Downloaded by University of Western Ontario on 06/01/2014 03:45:06.

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 and c = 17.297 0.023 A , c being the b = 4.974 0.001 A

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

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

Marianne Labet was born in Angouleme, France, in 1983. She studied paper and printing engineering at the Ecole Franc aise 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.

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.
This journal is
c

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

The Royal Society of Chemistry 2009

View Article Online

Properties of PCL Range 530630 000 1.0711.200 (65)(60) 5665 350 100130 0.9 4785 0.210.44 201000 Ref. 1,36 35, 7 and 8 38 9 5 1 3, 5, 6 and 8 3 and 5 1, 3, 5, 6 and 8

Table 1

Properties 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/%)

Published on 25 September 2009. Downloaded by University of Western Ontario on 06/01/2014 03:45:06.

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

This journal is

The Royal Society of Chemistry 2009

Chem. Soc. Rev., 2009, 38 , 34843504 | 3485

View Article Online

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

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

Published on 25 September 2009. Downloaded by University of Western Ontario on 06/01/2014 03:45:06.

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

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

3486 | Chem. Soc. Rev., 2009, 38, 34843504

This journal is

The Royal Society of Chemistry 2009

View Article Online

Scheme 6 Mechanism of the initiation step for coordinationinsertion ROP, adapted from Khanna et al.29 and Stridsberg et al.28

Published on 25 September 2009. Downloaded by University of Western Ontario on 06/01/2014 03:45:06.

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
This journal is
c

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
Chem. Soc. Rev., 2009, 38 , 34843504 | 3487

The Royal Society of Chemistry 2009

View Article Online

Published on 25 September 2009. Downloaded by University of Western Ontario on 06/01/2014 03:45:06.

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

3488 | Chem. Soc. Rev., 2009, 38, 34843504

This journal is

The Royal Society of Chemistry 2009

View Article Online

Published on 25 September 2009. Downloaded by University of Western Ontario on 06/01/2014 03:45:06.

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. czyk and co-workers used a methylaluminoxane Florjan 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

This journal is

The Royal Society of Chemistry 2009

Chem. Soc. Rev., 2009, 38 , 34843504 | 3489

View Article Online

Published on 25 September 2009. Downloaded by University of Western Ontario on 06/01/2014 03:45:06.

czyk et al.49 Scheme 14 Mechanism of the initiation step of the ROP of e-CL initiated/catalysed by methylaluminoxane, adapted from Flojan

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

3490 | Chem. Soc. Rev., 2009, 38, 34843504

This journal is

The Royal Society of Chemistry 2009

View Article Online

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
This journal is
c

Published on 25 September 2009. Downloaded by University of Western Ontario on 06/01/2014 03:45:06.

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
Chem. Soc. Rev., 2009, 38 , 34843504 | 3491

The Royal Society of Chemistry 2009

View Article Online

Published on 25 September 2009. Downloaded by University of Western Ontario on 06/01/2014 03:45:06.

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

3492 | Chem. Soc. Rev., 2009, 38, 34843504

This journal is

The Royal Society of Chemistry 2009

View Article Online

Scheme 22 Formation of a dormant chain during the polymerisation of e-CL catalysed by tin octoate.81

Published on 25 September 2009. Downloaded by University of Western Ontario on 06/01/2014 03:45:06.

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

This journal is

The Royal Society of Chemistry 2009

Chem. Soc. Rev., 2009, 38 , 34843504 | 3493

View Article Online

Published on 25 September 2009. Downloaded by University of Western Ontario on 06/01/2014 03:45:06.

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

3494 | Chem. Soc. Rev., 2009, 38, 34843504

This journal is

The Royal Society of Chemistry 2009

View Article Online

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. Mo ller 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

Published on 25 September 2009. Downloaded by University of Western Ontario on 06/01/2014 03:45:06.

Scheme 27 Formation of 2 polymeric chains for 1 molecule of catalyst during the ROP of e-CL using a titanium(IV) complex.99

This journal is

The Royal Society of Chemistry 2009

Chem. Soc. Rev., 2009, 38 , 34843504 | 3495

View Article Online

Published on 25 September 2009. Downloaded by University of Western Ontario on 06/01/2014 03:45:06.

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
3496 | Chem. Soc. Rev., 2009, 38, 34843504

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
This journal is
c

The Royal Society of Chemistry 2009

View Article Online

Published on 25 September 2009. Downloaded by University of Western Ontario on 06/01/2014 03:45:06.

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
This journal is
c

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

The Royal Society of Chemistry 2009

Chem. Soc. Rev., 2009, 38 , 34843504 | 3497

View Article Online

Published on 25 September 2009. Downloaded by University of Western Ontario on 06/01/2014 03:45:06.

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

3498 | Chem. Soc. Rev., 2009, 38, 34843504

This journal is

The Royal Society of Chemistry 2009

View Article Online

Published on 25 September 2009. Downloaded by University of Western Ontario on 06/01/2014 03:45:06.

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

This journal is

The Royal Society of Chemistry 2009

Chem. Soc. Rev., 2009, 38 , 34843504 | 3499

View Article Online

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,
This journal is
c

Published on 25 September 2009. Downloaded by University of Western Ontario on 06/01/2014 03:45:06.

The Royal Society of Chemistry 2009

View Article Online

Published on 25 September 2009. Downloaded by University of Western Ontario on 06/01/2014 03:45:06.

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

This journal is

The Royal Society of Chemistry 2009

Chem. Soc. Rev., 2009, 38 , 34843504 | 3501

View Article Online

11 D. R. Chen, J. Z. Bei and S. G. Wang, Polym. Degrad. Stab., 2000, 67, 455459. 12 C. De Kesel, C. V. Wauven and C. David, Polym. Degrad. Stab., 1997, 55, 107113. 13 P. Joshi and G. Madras, Polym. Degrad. Stab., 2008, 93, 19011908. 14 J. Pen a, T. Corrales, I. Izquierdo-Barba, A. L. Doadrio and M. Vallet-Reg , Polym. Degrad. Stab., 2006, 91, 14241432. 15 M. J. Jenkins, K. L. Harrison, M. M. C. G. Silva, M. J. Whitaker, K. M. Shakeshe and S. M. Howdle, Eur. Polym. J., 2006, 42, 31453151. 16 D. W. Hutmacher, T. Schantz, I. Zein, K. W. Ng, S. Hin, T. Kim and C. Tan, J. Biomed. Mater. Res., 2001, 55, 203216. 17 J. L. Hedrick, T. Magbitang, E. F. Connor, T. Glauser, W. Volksen, C. J. Hawker, V. Y. Lee and R. D. Miller, Chem.Eur. J., 2002, 8, 33083319. 18 S. M. Thomas, R. DiCosimo and V. Nagarajan, Trends Biotechnol., 2002, 20, 238242. 19 M. C. Rocca, G. Carr, A. B. Lambert, D. J. Macquerrie and J. H. Clark, US Pat., 6,531,615 B2, 2003. 20 B. Buchholz, DE Pat., 4005415, 1991. 21 K. Enomoto, M. Ajioka and A. Yamaguchi, WO Pat., 9312160, 1993. 22 E. M. Filachione and C. H. Fisher, US Pat., 2396994, 1946. 23 E. M. Filachione and C. H. Fisher, US Pat., 2447693, 1948. 24 Y. Yoshida, M. Miyamoto, S. Obuchi, K. Ikeda and M. Ohta, EP Pat., 0710684, 1996. 25 C. Braud, R. Devarieux, A. Atlan, C. Ducos and V. Michel, J. Chromatogr., B: Biomed. Sci. Appl., 1998, 706, 7382. 26 A. Mahapatro, A. Kumar and R. A. Gross, Biomacromolecules, 2004, 5, 6268. 27 H. Dong, H.-d. Wang, S.-g. Cao and J.-c. Shen, Biotechnol. Lett., 1998, 20, 905908. 28 K. M. Stridsberg, M. Ryner and A.-C. Albertsson, Adv. Polym. Sci., 2002, 157, 4165. 29 A. Khanna, Y. Sudha, S. Pillai and S. Rath, J. Mol. Model., 2008, 14, 367374. 30 T. Endo, in Handbook of Ring-Opening Polymerization, ed. P. Dubois, O. Coulembier and J.-M. Raquez, Wiley-VCH, Weinheim, 2009, pp. 5363. 31 M. S. Kim, K. S. Seo, G. Khang and H. B. Lee, Macromol. Rapid Commun., 2005, 26, 643648. 32 R. H. Platel, L. M. Hodgson and C. K. Williams, Polym. Rev., 2008, 48, 1163. 33 A. Bhaw-Luximon, D. Jhurry, S. Motala-Timol and Y. Lochee, Macromol. Symp., 2005, 231, 6068. 34 T. Kitayama, H. Yamaguchi, T. Kanzawa and T. Hirano, Polym. Bull., 2000, 45, 97104. 35 X. Deng, M. Yuan, C. Xiong and X. Li, J. Appl. Polym. Sci., 1999, 73, 14011408. 36 M. Yuan, C. Xiong and X. Deng, J. Appl. Polym. Sci., 1998, 67, 12731276. 37 A.-F. Mingotaud, F. Dargelas and F. Cansell, Macromol. Symp., 2000, 153, 7786. 38 E. Browning, Toxicity of industrial metals, Butterworth, London, 2nd edn, 1969. 39 L. F. Sanchez-Barba, A. Garces, M. Fajardo, C. Alonso-Moreno, J. Fernandez-Baeza, A. Otero, A. Antinolo, J. Tejeda, A. LaraSanchez and M. I. Lopez-Solera, Organometallics, 2007, 26, 64036411. 40 T.-L. Yu, C.-C. Wu, C.-C. Chen, B.-H. Huang, J. Wu and C.-C. Lin, Polymer, 2005, 46, 59095917. 41 B.-T. Ko and C.-C. Lin, J. Am. Chem. Soc., 2001, 123, 79737977. 42 M.-L. Shueh, Y.-S. Wang, B.-H. Huang, C.-Y. Kuo and C.-C. Lin, Macromolecules, 2004, 37, 51555162. 43 Z. Zhong, P. J. Dijkstra, C. Birg, M. Westerhausen and J. Feijen, Macromolecules, 2001, 34, 38633868. 44 L. Piao, M. Deng, X. Chen, L. Jiang and X. Jing, Polymer, 2003, 44, 23312336. 45 G. Rong, M. Deng, C. Deng, Z. Tang, L. Piao, X. Chen and X. Jing, Biomacromolecules, 2003, 4, 18001804. 46 Z. Tang, X. Chen, Q. Liang, X. Bian, L. Yang, L. Piao and X. Jing, J. Polym. Sci., Part A: Polym. Chem., 2003, 41, 19341941.

Published on 25 September 2009. Downloaded by University of Western Ontario on 06/01/2014 03:45:06.

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.

References
1 J. O. Iroh, in Polymer Data Handbook, ed. J. E. Mark, Oxford University Press, New York, 1999, pp. 361362. 2 H. Bittiger, R. H. Marchessault and W. D. Niegisch, Acta Crystallogr., Sect. B: Struct. Crystallogr. Cryst. Chem., 1970, 26, 19231927. 3 K. Van de Velde and P. Kiekens, Polym. Test., 2002, 21, 433442. 4 Sigma Aldrich, Polycaprolactone, Technical Specications, http://www.sigmaaldrich.com/united-kingdom.html. 5 Birmingham polymers, Chemical & Physical properties, http://www.birminghampolymers.com/. 6 R. A. Gross and B. Kalra, Science, 2002, 297, 803807. 7 V. R. Sinha, K. Bansal, R. Kaushik, R. Kumria and A. Trehan, Int. J. Pharm., 2004, 278, 123. 8 Y. Ikada and H. Tsuji, Macromol. Rapid Commun., 2000, 21, 117132. 9 C. X. F. Lam, S. H. Teoh and D. W. Hutmacher, Polym. Int., 2007, 56, 718728. 10 R. Chandra and R. Rustgi, Prog. Polym. Sci., 1998, 23, 12731335.

3502 | Chem. Soc. Rev., 2009, 38, 34843504

This journal is

The Royal Society of Chemistry 2009

View Article Online

47 Y. Wang and M. Kunioka, Macromol. Symp., 2005, 224, 193206. 48 P. Dubois, P. Degee, R. Jerome and P. Teyssie, Macromolecules, 1992, 25, 26142618. czyk, A. Plichta and M. Sobczak, Polymer, 2006, 47, 49 Z. Florjan 10811090. 50 A. Duda, Z. Florjanczyk, A. Hofman, S. Slomkowski and S. Penczek, Macromolecules, 1990, 23, 16401646. 51 V. Bergeot, T. Tassaing, M. Besnard, F. Cansell and A.-F. Mingotaud, J. Supercrit. Fluids, 2004, 28, 249261. 52 A. Duda, Macromolecules, 1996, 29, 13991406. 53 A. Duda and S. Penczek, Macromolecules, 1995, 28, 59815992. 54 A. Duda and S. Penczek, Macromol. Rapid Commun., 1995, 16, 6776. 55 H. R. Kricheldorf, M. Berl and N. Scharnagl, Macromolecules, 1988, 21, 286293. ro 56 E. Martin, P. Dubois and R. Je me, Macromolecules, 2003, 36, 70947099. 57 C. Miola-Delaite and T. H. R. Spitz, Macromol. Chem. Phys., 1999, 200, 17711778. 58 N. Ropson, P. Dubois, R. Jerome and P. Teyssie, Macromolecules, 1995, 28, 75897598. ro 59 D. Mecerreyes and R. Je me, Macromol. Chem. Phys., 1999, 200, 25812590. ro 60 A. Duda, S. Penczek, P. Dubois, D. Mecerreyes and R. Je me, Macromol. Chem. Phys., 1996, 197, 12731283. 61 N. Ropson, P. Dubois, R. Jerome and P. Teyssie, Macromolecules, 1993, 26, 63786385. 62 N. Ropson, P. Dubois, R. Jerome and P. Teyssie, Macromolecules, 1994, 27, 59505956. 63 P. Dubois, N. Ropson, R. Jerome and P. Teyssie, Macromolecules, 1996, 29, 19651975. 64 C. Jacobs, P. Dubois, R. Jerome and P. Teyssie, Macromolecules, 1991, 24, 30273034. 65 M. Akatsuka, T. Aida and S. Inoue, Macromolecules, 1995, 28, 13201322. 66 I. Taden, H.-C. Kang, W. Massa and J. Okuda, J. Organomet. Chem., 1997, 540, 189192. 67 A. Arbaoui, C. Redshaw and D. L. Hughes, Chem. Commun., 2008, 47174719. 68 N. Iwasa, J. Liu and K. Nomura, Catal. Commun., 2008, 9, 11481152. 69 N. Nomura, T. Aoyama, R. Ishii and T. Kondo, Macromolecules, 2005, 38, 53635366. 70 W. Yao, Y. Mu, A. Gao, Q. Su, Y. Liu and Y. Zhang, Polymer, 2008, 49, 24862491. 71 M. Endo, T. Aida and S. Inoue, Macromolecules, 1987, 20, 29822988. 72 C.-H. Huang, F.-C. Wang, B.-T. Ko, T.-L. Yu and C.-C. Lin, Macromolecules, 2001, 34, 356361. 73 B.-T. Ko and C.-C. Lin, Macromolecules, 1999, 32, 82968300. 74 Y.-C. Liu, B.-T. Ko and C.-C. Lin, Macromolecules, 2001, 34, 61966201. 75 S.-M. Lai, T.-M. Don, Y.-H. Liu and W.-Y. Chiu, J. Appl. Polym. Sci., 2006, 102, 30173027. 76 S. Dagorne, F. Le Bideau, R. Welter, S. Bellemin-Laponnaz and A. Maisse-Franc ois, Chem.Eur. J., 2007, 13, 32023217. nge and J. L. Hedrick, J. Polym. Sci., Part A: 77 M. Mo ller, R. Ka Polym. Chem., 2000, 38, 20672074. 78 M. Degirmenci, G. Hizal and Y. Yagci, Macromolecules, 2002, 35, 82658270. 79 M. Degirmenci, O. Izgin and Y. Yagci, J. Polym. Sci., Part A: Polym. Chem., 2004, 42, 33653372. 80 B. Kiskan and Y. Yagci, Polymer, 2005, 46, 1169011697. 81 A. Kowalski, A. Duda and S. Penczek, Macromol. Rapid Commun., 1998, 19, 567572. 82 A. Duda, S. Penczek, A. Kowalski and J. Libiszowski, Macromol. Symp., 2000, 153, 4153. 83 A. Kowalski, A. Duda and S. Penczek, Macromolecules, 2000, 33, 689695. 84 J. Libiszowski, A. Kowalski, A. Duda and S. Penczek, Macromol. Chem. Phys., 2002, 203, 16941701. 85 A. D. Celiz and O. A. Scherman, Macromolecules, 2008, 41, 41154119. 86 D. Bratton, M. Brown and S. M. Howdle, Macromolecules, 2005, 38, 11901195. 87 A. Kowalski, J. Libiszowski, T. Biela, M. Cypryk, A. Duda and S. Penczek, Macromolecules, 2005, 38, 81708176. 88 F. Stassin, O. Halleux and R. Jerome, Macromolecules, 2001, 34, 775781. 89 F. Stassin and R. Jerome, Chem. Commun., 2003, 232233. 90 M. Mo ller, F. Nederberg, L. S. Lim, R. Kange, C. J. Hawker, J. L. Hedrick, Y. Gu, R. Shah and N. L. Abbott, J. Polym. Sci., Part A: Polym. Chem., 2001, 39, 35293538. 91 I. Barakat, P. Dubois, R. Jerome and P. Teyssie, Macromolecules, 1991, 24, 65426545. 92 Y. Sarazin, M. Schormann and M. Bochmann, Organometallics, 2004, 23, 32963302. 93 L. Liao, L. Liu, C. Zhang and S. Gong, Macromol. Rapid Commun., 2006, 27, 20602064. 94 P. Dobrzynski, Polymer, 2007, 48, 22632279. 95 B. J. OKeefe, L. E. Breyfogle, M. A. Hillmyer and W. B. Tolman, J. Am. Chem. Soc., 2002, 124, 43844393. 96 M. G. Davidson, M. D. Jones, M. D. Lunn and M. F. Mahon, Inorg. Chem., 2006, 45, 22822287. 97 A. J. Chmura, M. G. Davidson, M. D. Jones, M. D. Lunn and M. F. Mahon, Dalton Trans., 2006, 887889. 98 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, 72507257. 99 D. Takeuchi, T. Nakamura and T. Aida, Macromolecules, 2000, 33, 725729. geault 100 Y. Mahha, A. Atlamsani, J.-C. Blais, M. Tessier, J.-M. Bre and L. Salles, J. Mol. Catal. A: Chem., 2005, 234, 6373. 101 N. Nomura, A. Taira, T. Tomioka and M. Okada, Macromolecules, 2000, 33, 14971499. 102 N. Nomura, A. Taira, A. Nakase, T. Tomioka and M. Okada, Tetrahedron, 2007, 63, 84788484. 103 X. M. Deng, Z. Zhu, C. Xiong and L. Zhang, J. Appl. Polym. Sci., 1997, 64, 12951299. 104 W. M. Stevels, M. J. K. Ankone, P. J. Dijkstra and J. Feijen, Macromolecules, 1996, 29, 82968303. 105 O. Poncelet, W. J. Sartain, L. G. Hubert-Pfalzgraf, K. Folting and K. G. Caulton, Inorg. Chem., 1989, 28, 263267. 106 S. Agarwal, M. Karl, K. Dehnicke, G. Seybert, W. Massa and A. Greiner, J. Appl. Polym. Sci., 1999, 73, 16691674. 107 W. Lin, W. L. Sun and Z. Q. Shen, Chin. Chem. Lett., 2007, 18, 11331136. 108 M. Nishiura, Z. Hou, T.-a. Koizumi, T. Imamoto and Y. Wakatsuki, Macromolecules, 1999, 32, 82458251. 109 M. Yamashita, Y. Takemoto, E. Ihara and H. Yasuda, Macromolecules, 1996, 29, 17981806. 110 E. Martin, P. Dubois and R. Jerome, Macromolecules, 2000, 33, 15301535. 111 E. Martin, P. Dubois and R. Jerome, Macromolecules, 2003, 36, 59345941. 112 W. M. Stevels, M. J. K. Ankone, P. J. Dijkstra and J. Feijen, Macromolecules, 1996, 29, 33323333. 113 S. Kobayashi, J. Polym. Sci., Part A: Polym. Chem., 1999, 37, 30413056. 114 S. Kobayashi, H. Uyama and M. Ohmae, Bull. Chem. Soc. Jpn., 2001, 74, 613635. 115 R. T. MacDonald, S. K. Pulapura, Y. Y. Svirkin, R. A. Gross, D. L. Kaplan, J. Akkara, G. Swift and S. Wolk, Macromolecules, 1995, 28, 7378. 116 G. A. R. Nobes, R. J. Kazlauskas and R. H. Marchessault, Macromolecules, 1996, 29, 48294833. 117 G. Sivalingam and G. Madras, Biomacromolecules, 2004, 5, 603609. 118 H. Dong, S.-G. Cao, Z.-Q. Li, S.-P. Han, D.-L. You and J.-C. Shen, J. Polym. Sci., Part A: Polym. Chem., 1999, 37, 12651275. 119 H. Dong, Z. Wang, Z.-Q. Li, D.-L. You, S.-P. Han, S.-G. Cao and J.-C. Shen, Ann. N. Y. Acad. Sci., 1998, 864, 263266. 120 S. Kobayashi, H. Uyama and S. Namekawa, Polym. Degrad. Stab., 1998, 59, 195201. 121 S. Kobayashi, H. Uyama, S. Namekawa and H. Hayakawa, Macromolecules, 1998, 31, 56555659. 122 H. Uyama, S. Suda, H. Kikuchi and S. Kobayashi, Chem. Lett., 1997, 26, 11091110.

Published on 25 September 2009. Downloaded by University of Western Ontario on 06/01/2014 03:45:06.

This journal is

The Royal Society of Chemistry 2009

Chem. Soc. Rev., 2009, 38 , 34843504 | 3503

View Article Online

123 S. Kobayashi, K. Takeya, S. Suda and H. Uyama, Macromol. Chem. Phys., 1998, 199, 17291736. 124 H. Uyama, K. Takeya and S. Kobayashi, Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci., 1993, 69, 203207. 125 H. Uyama, K. Takeya and S. Kobayashi, Bull. Chem. Soc. Jpn., 1995, 68, 5661. 126 J. R. Govan and V. Deretic, Microbiol. Rev., 1996, 60, 539574. 127 A. Kumar and R. A. Gross, Biomacromolecules, 2000, 1, 133138. 128 Y. Mei, A. Kumar and R. A. Gross, Macromolecules, 2002, 35, 54445448. rdova, T. Iversen, K. Hult and M. Martinelle, Polymer, 129 A. Co 1998, 39, 65196524. rdova, T. Iversen and K. Hult, Macromolecules, 1998, 31, 130 A. Co 10401045. 131 F. C. Loeker, C. J. Duxbury, R. Kumar, W. Gao, R. A. Gross and S. M. Howdle, Macromolecules, 2004, 37, 24502453. 132 C. Hedfors, E. Ostmark, E. Malmstrom, K. Hult and M. Martinelle, Macromolecules, 2005, 38, 647649. 133 K. S. Bisht, F. Deng, R. A. Gross, D. L. Kaplan and G. Swift, J. Am. Chem. Soc., 1998, 120, 13631367. 134 B. G. G. Lohmeijer, R. C. Pratt, F. Leibfarth, J. W. Logan, D. A. Long, A. P. Dove, F. Nederberg, J. Choi, C. Wade, R. M. Waymouth and J. L. Hedrick, Macromolecules, 2006, 39, 85748583. 135 R. C. Pratt, B. G. G. Lohmeijer, D. A. Long, R. M. Waymouth and J. L. Hedrick, J. Am. Chem. Soc., 2006, 128, 45564557. 136 A. Chuma, H. W. Horn, W. C. Swope, R. C. Pratt, L. Zhang, B. G. G. Lohmeijer, C. G. Wade, R. M. Waymouth, J. L. Hedrick and J. E. Rice, J. Am. Chem. Soc., 2008, 130, 67496754. 137 L. Zhang, F. Nederberg, R. C. Pratt, R. M. Waymouth, J. L. Hedrick and C. G. Wade, Macromolecules, 2007, 40, 41544158. 138 J. Casas, P. V. Persson, T. Iversen and A. Cordova, Adv. Synth. Catal., 2004, 346, 10871089. 139 P. V. Persson, J. Schroder, K. Wickholm, E. Hedenstrom and T. Iverson, Macromolecules, 2004, 37, 58895893. 140 Y. Shibasaki, H. Sanada, M. Yokoi, F. Sanda and T. Endo, Macromolecules, 2000, 33, 43164320. 141 S. Gazeau-Bureau, D. Delcroix, B. Martin-Vaca, D. Bourissou, C. Navarro and S. Magnet, Macromolecules, 2008, 41, 37823784.

Published on 25 September 2009. Downloaded by University of Western Ontario on 06/01/2014 03:45:06.

3504 | Chem. Soc. Rev., 2009, 38, 34843504

This journal is

The Royal Society of Chemistry 2009