Patent Application
20120136124
The present invention relates to the field of di-, tri- and multi-block polyesters/polycarbonates copolymers based on the use of hydroxyl-end capped polyesters/polycarbonates as transfer agents and macro-initiators.
There is an obvious need for polymer materials based on renewable resources and efficient processes for preparing them. Of particular interest are block copolymers which allow, upon adjusting the size and nature of each block, tuning of the physical properties to obtain very specific physical properties, for instance phase separation of blocks. As an example, diblock and triblock polycarbonate-polyesters that combine a soft poly(trimethylene carbonate) block (PTMC) and hard, crystallisable poly(L- or D-lactide) blocks (PLLA, PDLA), thus forming so-called thermoplastic elastomers, are biodegradable and biocompatible and thus find applications as biomaterials.
The synthesis of linear or star polycarbonates hydroxy-capped at each arm terminus is briefly documented in literature in the case of poly(trimethylene carbonate). The preparation of linear telechelic dihydroxy HO—PTMC—OH and 3-arms star trihydroxy R—(PTMC—OH)3 polymers has been achieved by the ring-opening polymerization (ROP) of TMC in the presence of tin-based catalysts such as SnOct2 (Oct=octanoate, 2-ethylhexanoate), and a diol or a triol respectively, such as 1,4-butanediol as described for instance in Fredrik Nederberg, Joens Hilborn and Tim Bowden, Macromolecules 2006, 39, 3907-3913, or triethyleneglycol as reported in Jan Lukaszczyk, Piotr Jelonek and Barbara Trzebicka, Pol. Polimery 2008, 53, 433-439, or 1,6-hexanediol or glycerol as reported in Zheng Zhang, Dirk W. Grijpma and Jan Feijen, Macromol. Chem. Phys., 2004, 205, 867-875, and in Patricia Y. W. Dankers, Zheng Zhang, Eva Wisse, Dirk W. Grijpma, Rint P. Sijbesma, Jan Feijen and E. W. Meijer Macromolecules, 2006, 39, 8763-8771 (Scheme 1). These reactions typically proceed at a temperature higher than 100° C. for a couple of hours. They are schematically represented in scheme 1.
In some cases, macrodiols HO—X—OH have also been used as initiators/transfer agents to prepare linear telechelic dihydroxy HO—PTMC—X—PTMC—OH polymers, by ROP of TMC in the presence of tin catalysts, as described for instance with poly(ethylene glycol) (HO-PEG-OH) in Ying Zhang and Ren-Xi Zhuo, Biomaterials 2005, 26, 2089-2094, or in H. Morinaga, B Ochiai, H. Mori, T. Endo, J. Polym. Sci. 2006, 1958-1996 or with dihydroxy end-capped poly(caprolactone) (HO—PCL-OH) as described in Yong Tang Jia, Hak Yong Kim, Jian Gong, Duok Rae Lee and Bin Ding, Polymer Intern. 2004, 53, 312-319, or to prepare Y-shaped X—(PTMC—OH)2 copolymers as reported with the ROP of TMC from poly(ethylene glycol)-CH—(CH2OH)2 and ZnEt2 in Huai-Hong Zhang, Zi-Qun Huang, Bai-Wang Sun, Jia-Xiu Guo, Jian-Li Wang, Yao-Qiang Chen, J. Polym. Sci. 2008, 46, 8131-8140.
It has been reported that those linear telechelic dihydroxy HO—PTMC—OH and 3-arms star trihydroxy R—(PTMC—OH)3 polymers can act as macroinitiators for the preparation of multiblock polycarbonate-polyester copolymers. Thus, PLA-PTMC-PLA triblock copolymers based on TMC and lactide as biodegradable thermoplastic elastomers have been prepared starting from linear telechelic dihydroxy HO—PTMC—OH polymers, lactide (either L-, D- or D,L-LA) and SnOct2 as the catalyst, as reported in Zheng Zhang, Dirk W. Grijpma and Jan Feijen, Macromol. Chem. Phys., 2004, 205, 867-875. It is represented in scheme 2.
The preparation of triblock Polyester-PTMC-Polyester copolymers, wherein polyester can be PHB=poly(3-hydroxybutyrate) (PHB) or, poly(caprolactone) (PCL), or poly(valerolactone) (PVL), or poly(lactide) (PLA) has been reported in Hans R. Kricheldorf and Andrea Stricker, Macromol. Chem. Phys., 1999, 200, 1726-1733. The method used involved the sequential addition of TMC and then BBL (BBL=rac-beta-butyrolactone) or VL (δ-valerolactone) or CL (ε-caprolactone) or LA (lactide) onto the tin-based di-initiator 2,2-dibutyl-2-stanna-1,3-dioxepane (DSDOP). In this process, a stoechiometric amount of tin vs macromolecules is used to prepare the ABA-type block copolymer, and there was no use of any alcohol or macrodiols as transfer agents.
It is an aim of the present invention to use polyesters or polycarbonates macrodiols as co-initiator and chain transfer agent in the immortal ring-opening polymerization of the comonomer.
It is an aim of the present invention to provide di-, tri-, or multi-block polyester/polycarbonate copolymers.
It is also an aim of the present invention to prepare fully biodegradable di-, tri-, or multi-block linear, branched or star-shaped polyester/polycarbonate copolymers.
It is a further aim of the present invention to tailor di-, tri-, or multi-block copolymers with desired properties.
Any one of these aims is, at least partially, fulfilled by the present invention.
Accordingly, the present invention discloses a process for preparing di-, tri, or multi-block polyester/polycarbonate (PC) copolymers by ring-opening polymerisation in the presence of a catalyst system comprising a compound selected from a Lewis acidic metal salt or a metal complex or a metal-free organic base, said process further comprising either a linear monohydroxy HO—PC—OR, or a linear telechelic dihydroxy HO—PC—OH, or a star polyhydroxy R—(PC—OH)n end-capped polycarbonate acting both as transfer agent and as co-initiator via hydroxyl group(s), wherein PC is a polycarbonate chain obtained by ring-opening polymerisation of a cyclic ester or carbonate monomer.
The present invention discloses a process for preparing di-, tri, or multi-block polyester/polycarbonate polymers by immortal ring-opening polymerisation that comprises the steps of:
The macro-polyol plays two roles:
The solvent is typically selected from toluene, xylene, THF or methylcyclohexane.
The metal complexes acting as catalyst systems can be selected from single-site catalyst components based upon a bulky β-diiminate ligands (BDI) as described by Coates et al. (B. M. Chamberlain, M. Cheng, D. R. Moore, T. M. Ovitt, E. B. Lobkovsky, and G. W. Coates, in J. Am. Chem. Soc., 2001, 123, 3229) and represented by general formula:
wherein R1, R2, R3, R4, R5, R6 and R7 are each independently selected from hydrogen, unsubstituted or substituted hydrocarbyl, or inert functional group and wherein two or more of said groups can be linked together to form one or more rings, wherein X is an hydrocarbyl radical having from 1 to 12 carbon atoms, an alkoxide group OR*, an amido group NR**2 or a borohydride group (BH4).
Among the preferred catalytic compounds of that category, one can further cite [BDI]Zn(N(SiMe3)2), {[BDI]Zn(OiPr),}2, Zn(N(SiMe3)2), ZnEt2, Ln(N(SiMe3)2)3 (Ln=group III metals, including the lanthanide series), “Ln(OiPr)3”, Al(OiPr)3, Mg[N(SiMe3)2]2, Ca[N(SiMe3)2]2(THF)2, (BDI)Fe[N(SiMe3)2], Fe[N(SiMe3)2]2, and Fe[N(SiMe3)2]3.
They act by a coordination/insertion mechanism.
The metallic salt can be selected from metallic complexes of formula M(OSO2CF3)n, hereafter referred to as triflates or OTf or M(N(OSO2CF3)2)n, hereafter referred to as triflimidates or NTf2 or M(RC(O)CR2C(O)R)n, hereafter referred to as acetylacetonates or acac or (R″CO2)nM, hereafter referred to as carboxylates, wherein M is a metal Group 2, 3, including the lanthanide series, hereafter referred as Ln, 4, 12, 13, 14 or 15 of the periodic Table, wherein each R is selected independently from a linear or branched hydrocarbyl radical having from 1 to 12 carbon atoms, substituted or not by for instance an halogen or heteroatom, wherein each R″ is selected independently from a perfluorinated alkyl or aryl residue having from 1 to 12 carbon atoms, and wherein n is the valence of M.
Preferably, M is Mg(II), Ca(II), Sc(III), Ln(III), Y(III), Sm(III), Yb(III), Ti(IV), Zr(IV), Fe(II), Fe(III), Zn(II), Al(III), Sn(IV) or Bi(III). More preferably, it is Al, Bi, Zn or Sc, Al being the most efficient metal.
Preferably each R is selected independently from alkyl group such as CH3 or a substituted alkyl group such as CF3, More preferably, they are all the same and they are CR3 or CF3.
Preferably, R″ is (C6F5) or (CF3), or CF3(CF2)m, wherein m is an integer from 1 to 6.
Among the preferred catalytic compounds according to the present invention, one can cite Al(OTf)3, Al(NTf2)3, Mg(OTf)2, Ca(OTf)2, Zn(OTf)2, Sc(OTf)3, Bi(OTf)3, Fe(acac)3, Al(OCOCF3)3, Zn(OCOCF3)2, Zn(BF4)2, Zn(acac)2.
These catalysts act by an activated monomer pathway, in the combination with an external nucleophile, typically the PC—(OH)n compound.
The non-metallic organic compounds can be selected, as non limitative examples, from dimeric phosphazene bases as disclosed for example in Zhang et al. (Zhang L, Nederberg F., Messman J. M., Pratt R. C., Hedrick J. L., and Wade C. G., in J. Am. Chem. Soc., 2007, 129, 12610-12611) or phosphazene bases as disclosed for example in Zhang et al. (Zhang L., Nederberg F., Pratt R. C., Waymouth R. M., Hedrick J. L., and Wade C. G., in Macromolecules 2007, 40, 4154-4158) or organic compounds such as amines or guanidine as described for example in Nederberg et al. (Nederberg F., Lohmeijer G. B., Leibfarth F., Pratt R. C., Choi J., Dove A. P., Waymouth R. M., Heidrich J. L., in Biomacromolecules, 8, 153, 2007) or in Mindemark et al. (Mindemark J., Hilborn J., Bowden T., in Macromolecules, 40, 3515, 2007).
In addition, the amount of catalyst system is minimised with respect to the amount of monomer leading to polymers bearing less metallic traces than the tin-based catalysts of the prior art, for the production of related block copolymers. The ratio monomer to catalyst system is of at least 100, preferably of at least 1000 and more preferably of at least 1500.
The alcohol can be represented by formula R′OH wherein R′ is an hydrocarbyl, linear or branched, having from 1 to 20 carbon atoms. Preferably R′ is a secondary alkyl residue or benzylic group, more preferably it is isopropyl (iPr) or benzyl (Bn). It can also be a poly-ol (diol, triol and higher functionality polyhydridic alcohols), typically 1,3-propanediol or trimethyloipropane, possibly derived from biomass such as glycerol or any other sugar based alcohol (erythritol, cyclodextrine) . . . All alcohols can be used individually or in combination.
The alcohol is used in excess with an alcohol to catalyst ratio of at least 5.
Hydroxy-end-capped polyester/polycarbonates can be prepared by ring-opening polymerisation (ROP) of a cyclic ester/carbonate monomer in the presence of a catalyst and an alcohol that acts as an initiator and as a transfer agent. When using a mono-alcohol R′OH, all polyesters/polycarbonates produced via this technique are thus capped at one end by a hydroxy group and at the other macromolecule terminus by a ester/carbonate moiety. For instance, HO—PTMC—OR homopolymers have been prepared in high yield by ROP of carbonate TMC, using as catalyst either (BDI)Zn[N(SiMe3)2], Al(OTf)3 or dimethylaminopyridine (DMAP), in the presence of an alcohol (R′OH) selected typically from BnOH or iPrOH, wherein PTMC is the polyTMC. The homopolymers have controlled molecular weights and narrow polydispersity. The reaction is presented schematically in scheme 3. When using a poly-ol, all polyesters/polycarbonates produced via this technique are thus capped at each ends by a hydroxy group.
Such hydroxy-end-capped HO—PTMC—OR′ homopolymers can be subsequently used as macro-initiators and transfer agents, to prepare with high efficiency a variety of diblock copolymers. The reactions are performed in the presence of a catalyst selected for example from (BDI)Zn[N(SiMe3)2] or Al(OTf)3 or an organic base such as DMAP and they allow the immortal ROP of cyclic polar monomers such as TMC, TMC(OMe)2, rac-BBL or lactides (LA) or any heterocyclic monomer among lactones, diesters, carbonates, morpholinediones. Some of these are represented in scheme 4, as non-limitative examples.
Alternatively, a variety of diblock AB, or triblock ABA, or multiblock . . . CABAC . . . copolymers can be prepared from the block copolymerization of monomers A, B, C . . . , using the corresponding monoalcohol, did, or poly-ol, respectively.
These reactions are carried out at a temperature ranging between room temperature (about 25° C.) and 150° C., preferably between 50 and 150° C., more preferably between 80 and 100° C. The temperature depends upon the nature of catalyst system and on the monomer. For example, aluminium-based systems are more tolerant but less active than zinc-based systems and thus demand a higher temperature than zinc-based systems. For example lactides are less reactive than TMC and thus also demand a higher temperature than TMC.
The controlled ROP of various cyclic monomers has been carried out using the (BDI)Zn[N(SiMe3)2]/HO—PTMC—OBn catalyst system. The polymerisation conditions and results are displayed in Table 1. The 1H and 13C NMR spectra are displayed respectively in
aDetermined by 1H NMR
bMn, theo = [Monomer]0/[HO-PTMC-OBn] × M[Monomer] × conversion + M(HO-PTMC-OBn). with MTMC = 102. g · mol−1, MTMC(OMe)2 = 162 g · mol−1, MBBL = 86 g · mol−1, and MLLA = 144 g · mol−1
cDetermined by SEC vs PS standards;
Due to the potential interest of the final copolymers, notably as modifiers of poly(lactide) (PLA) and/or as compatibilisers, special attention has been paid to the ROP of L-lactide (LLA) with such catalyst systems. A first series of investigations was carried out by using (BDI)Zn[N(SiMe3)2]/HO—PTMC—OBn catalyst system. All reactions were carried out at a temperature of 100° C., in a 4M solution of toluene, using rigorously purified LLA. It is represented in Scheme 5 and the results are reported in Table 2. The 1H NMR is represented in
200/1/10
5 500d
aDetermined by 1H NMR
bMntheo = [LLA]0/[HO-PTMC-OBn] × 144 × conversion + M(HO-PTMC-OBn)
cDetermined by SEC vs PS standards; Mn values corrected for hydrodynamic volume differences (correction coefficient 0.73 for PTMC and 0.58 for PLA).
dMn determined by 1H NMR = 4 270 g · mol−1
It must be noted that in examples 5, 6, 7, 8, 10 and 11, macromer HO—PTMC—OBn has been synthesised, precipitated and stocked before being used in the multi-block polymerisation. Consequently it has potentially absorbed water and has thus been potentially deteriorated, thereby explaining the poorer correlation between the theoretical and experimental values of number average molecular weight Mn. Examples 9 and 12, on the contrary were carried out by sequential reaction without preliminary isolation of HO-PTMC—OBn.
Mechanical Properties of Diblock Copolymers PTMC-PLLA Prepared with [(BDI)Zn[N(SiMe3)2]/HO—PTMC—OBn Catalyst System.
The mechanical properties of the copolymers were evaluated using compression-moulded sheets. The copolymers were moulded by mini max moulder of custom scientific instruments Inc at temperatures respectively of 180° C. for PLA and of 220° C. for PTMC.
Tensile tests were carried out on 6 samples of the same copolymer at room temperature according to ASTMD 882 by a ZWICK (MEC125/2) with load cell 200 N at a cross-head speed of 10 mm/min. Strength and elongation values at break were calculated based on the dynamic tensile diagrams. The sample specimen deformation was derived from the grip-to-grip separation, which was initially 10 mm. The results are presented in Table 3.
Thermal Properties of Diblock Copolymers PTMC-PLLA Prepared with (BDI)Zn[N(SiMe3)2]/HO—PTMC—OBn Catalyst System.
The thermal properties of the purified polymers were evaluated by differential scanning calorimetry (DSC 131, Setaram instrument). Experiments were performed in aluminium pans and helium was used as gas purge.
6-12 mg samples were used for DSC analysis. For the copolymers, samples were heated from −40° C. to 200° C. with a heating rate of 10° C./min, cooled down to −40° C. with a cooling rate of 10° C./min, and then heated again to 200° C. at the same heating rate. Melting (Tm) and glass transition (Tg) temperature of samples were obtained from the second heating curves. The results are summarised in Table 4.
Different, more robust and/or cheaper catalyst systems involving, instead of an organometallic catalyst precursor, a Lewis acidic metal salt or an organic base were also investigated. Aluminum triflate, DMAP and a phosphazene in combination with HO—PTMC—OBn were selected for those investigations in the ROP of technical-grade LLA. The reactions were carried out at a temperature of 130° C., in a 4M solution of toluene, with purified LLA. The results are summarized in Table 5.
200/1/5
9800 (1.23)
aDetermined by 1H NMR
bMn, theo = [LLA]0/[HO-PTMC-OBn] × 144 × conversion + M(HO-PTMC-OBn)
cDetermined by SEC vs PS standards;; Mn values corrected for hydrodynamic volume differences (correction coefficient 0.73 for PTMC and 0.58 for PLA).
dMn determined by 1H NMR = 3 410 g · mol−1
eExample 20 was conducted at a temperature of 100° C.
In examples 13, 15, 16, 17 and 19, macromer HO—PTMC—OBn has been synthesized, precipitated and stocked before being used in the multi-block polymerisation. In examples 14, 18 and 20, on the contrary polymerisation was carried out by sequential reaction without preliminary isolation of HO—PTMC—OBn.
A diol/triol was used in the ROP of a cyclic carbonate as initiator/transfer agent. The resulting polycarbonate contained two/three hydroxy chain-ends. (BDI)Zn[N(SiMe3)2], Al(OTf)3 or an organic base such as DMAP or a phosphazene were used as catalyst component and 1,3-propanediol or 1,4-benzenedimethanol or glycerol transfer agent/initiator. The ROP process is described in scheme 6.
The telechelic HO—PTMC—OH/R(PTMC—OH)3 homopolymers prepared in scheme 6 were used subsequently as transfer agent/initiator for the preparation of ABA/R(AB)3-type tri-block copolymers. This process was used in the preparation of HO—PLLA-PTMC-PLLA-OH triblock copolymers. The reactions have been conducted in highly concentrated toluene solutions and are represented in scheme 7. The results obtained using (BDI)Zn[N(SiMe3)2] as catalyst with purified LLA, and using aluminum triflate or DMAP or phosphazene as catalysts with technical grade LLA are summarised in Tables 4 and 5. For examples 21 to 24, displayed in Table 6, the reactions were carried out with (BDI)Zn[N(SiMe3)2] as catalyst at a temperature of 100° C. For examples 25 to 28, displayed in Table 5, the reactions were carried out at a temperature of 130° C. and the catalyst system is indicated in the Table.
200/1/5
200/1/5
200/1/5
aDetermined by 1H NMR
bMn, theo = [LLA]0/[HO-PTMC-OH]0 × 144 × conversion + M(HO-PTMC-OH).
cDetermined by SEC vs PS standards; Mn values corrected for hydrodynamic volume differences (correction coefficient 0.73 for PTMC and 0.58 for PLA).
Example 25 was carried out by sequential monomer addition without preliminary isolation of HO—PTMC—OH, like a block copolymerization using a diol as summarised in Table 7.
aDetermined by 1H NMR
bMn, theo = [LLA]0/[HO-PTMC-OH] × 144 × conversion + M(HO-PTMC-OH)
cDetermined by SEC vs PS standards; Mn values corrected for hydrodynamic volume differences (correction coefficient 0.73 for PTMC and 0.58 for PLA).
Examples 27 and 28 were conducted as sequential monomer addition without preliminary isolation of HO—PTMC—OH, like a block copolymerization using a diol
Example 29 was conducted at a temperature of 100° C.
Mechanical Properties of Triblock Copolymers PLLA-PTMC-PLLA Prepared with (BDI)Zn[N(SiMe3)2]/HO—PTMC—OH Catalyst System.
The mechanical properties are summarised in Table 8.
Thermal Properties of Triblock Copolymers PLLA-PTMC-PLLA Prepared with (BDI)Zn[N(SiMe3)2]/HO—PTMC—OH Catalyst System.
The thermal properties are summarised in Table 9.
Similarly, ABA-type triblock copolymers of HO—PTMC(OMe)2-PTMC-PTMC(OMe)2-OH were prepared by ROP of TMC(OMe)2 with (BDI)Zn[N(SiMe3)2]/HO—PTMC—OH catalyst system as represented in scheme 8. The reactions were carried out at a temperature of 60° C. with purified TMC(OMe)2. The results are summarised in Table 10.
aDetermined by 1H NMR
bMn, theo = [TMC(OMe)2]0/[HO-PTMC-OH] × 162 × conversion + M(HO-PTMC-OH)
cDetermined by SEC vs PS standards; Mn values uncorrected
Finally, HO—PHB—PTMC—PHB—OH ABA-type triblock copolymers were prepared by ROP of rac-BBL with (BDI)Zn[N(SiMe3)2]/HO—PTMC—OH catalyst system as represented in scheme 9. The reactions were carried out at a temperature of 60° C. with purified rac-BBL. The results are summarised in Table 11.
200/1/5
aDetermined by 1H NMR
bMn, theo = [LLA]0/[HO-PTMC-OH] × 86 × conversion + M(HO-PTMC-OH)
cDetermined by SEC vs PS standards; Mn values uncorrected
Example 32 was carried out by sequential monomer addition without preliminary isolation of HO—PTMC—OH, like a block copolymerization using a diol.
Other diblock copolymers were prepared as follows.
Their mechanical and thermal properties are presented respectively in Tables 12 and 13.
Starblock copolymers PLLA-PTMC-(PLLA)2 prepared with Zn(BDI)[N(SiMe3)2]/HO—PTMC(OH)2 catalyst system according to the scheme herebelow.
The mechanical and thermal properties are summarised respectively in Tables 14 and 15.
| Number | Date | Country | Kind |
|---|---|---|---|
| 08291193.4 | Dec 2008 | EP | regional |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/EP09/66029 | 11/30/2009 | WO | 00 | 8/5/2011 |
