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  • C07—ORGANIC CHEMISTRY
  • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
  • C07F3/00—Compounds containing elements of Groups 2 or 12 of the Periodic Table
  • C07F3/02—Magnesium compounds
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  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
  • C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
  • C08G63/78—Preparation processes
  • C08G63/82—Preparation processes characterised by the catalyst used
  • C08G63/85—Germanium, tin, lead, arsenic, antimony, bismuth, titanium, zirconium, hafnium, vanadium, niobium, tantalum, or compounds thereof
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  • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
  • C07F3/00—Compounds containing elements of Groups 2 or 12 of the Periodic Table
  • C07F3/06—Zinc compounds
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
  • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
  • B01J31/12—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing organo-metallic compounds or metal hydrides
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  • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
  • C07F7/02—Silicon compounds
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  • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
  • C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
  • C08G63/02—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds
  • C08G63/06—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds derived from hydroxycarboxylic acids
  • C08G63/08—Lactones or lactides
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  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
  • C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
  • C08G63/78—Preparation processes
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  • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
  • C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
  • C08G63/78—Preparation processes
  • C08G63/82—Preparation processes characterised by the catalyst used
  • C08G63/823—Preparation processes characterised by the catalyst used for the preparation of polylactones or polylactides
• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
  • C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
  • C08G63/78—Preparation processes
  • C08G63/82—Preparation processes characterised by the catalyst used
  • C08G63/83—Alkali metals, alkaline earth metals, beryllium, magnesium, copper, silver, gold, zinc, cadmium, mercury, manganese, or compounds thereof
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  • C08G64/00—Macromolecular compounds obtained by reactions forming a carbonic ester link in the main chain of the macromolecule
  • C08G64/02—Aliphatic polycarbonates
• • C—CHEMISTRY; METALLURGY
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  • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
  • C08G64/00—Macromolecular compounds obtained by reactions forming a carbonic ester link in the main chain of the macromolecule
  • C08G64/16—Aliphatic-aromatic or araliphatic polycarbonates
  • C08G64/1608—Aliphatic-aromatic or araliphatic polycarbonates saturated
• • C—CHEMISTRY; METALLURGY
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  • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
  • C08G64/00—Macromolecular compounds obtained by reactions forming a carbonic ester link in the main chain of the macromolecule
  • C08G64/20—General preparatory processes
  • C08G64/30—General preparatory processes using carbonates
• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
  • C08G64/00—Macromolecular compounds obtained by reactions forming a carbonic ester link in the main chain of the macromolecule
  • C08G64/20—General preparatory processes
  • C08G64/38—General preparatory processes using other monomers

Definitions

• the present invention discloses new catalyst systems based on complexes of divalent metals supported by chelating phenoxy Iigands for immortal ring-opening polymerisation of cyclic esters and cyclic carbonates.
• Ring-opening polymerisation (ROP) of cyclic esters has emerged as the most convenient way to generate bio-degradable aliphatic polyesters as described for example in Uhrich et al. (K. E. Uhrich, S. M. Cannizzaro, R. S. Langer, K. M. Shakesheff, Chem. Rev., 1999, 99, 3181-3198), or in Ikada and Tsujt (Y. ikada, H. Tsuji, Macromol. Rapid. Commun., 2000, 21, 117-132) or in Langer (R. Langer, Ace. Chem. Res., 2000, 33, 94-101) or in Okada (M. Okada, Prog. Polym. Sci., 2002, 27, 87-133).
• Uhrich et al. K. E. Uhrich, S. M. Cannizzaro, R. S. Langer, K. M. Shakesheff, Chem. Rev., 1999, 99, 3
• LA lactide
• Tin-based initiators based typically on tin(ll) 2-ethyl-hexanoate, are commonly used in industry for the ROP of LA and other cyclic monomers. These systems are slow, poorly controlled and present serious issues related to the heavy tin element, as discussed for example in Drumright et af. (R, E. Drumright, P. R. Gruber, D. E. Henton, Adv. Mater., 2000, 12, 1841-1846) or in Okada (M. Okada, Prog. Poiym, Sd., 2002, 27, 87-133).
• BBL ⁇ -butyrolactone
• BBL ⁇ -butyrolactone
• poly(3-hydroxybutyrate)s a naturally-occurring highly crystalline thermoplastic resin produced by several algae and bacteria as their isotactic stereoisomer
• some catalyst systems leading to syndiotactic polymers as discussed by Amgoume et al. A. (Amgoune, C. M. Thomas, S. ilinca, T. Roisnei, J.-F. Carpentier, Angew. Chem. Int. Ed, 2006, 45, 2782-2784), or by Rieth et al. (L. R. Rieth, D. R. Moore, E. B. Lobkovsky, G.
• trimethylene carbonate has also started to attract considerable attention in the past 3 years as disclosed in S. Matsumura Adv. Polym. ScL 2005, 194, 95-132, or in Hellaye et al. (M. Le Hellaye, N. Fortin, J. Guilloteau, A. Soum, S. Lecommandoux, S. M. Nicolas Blomacromolecules, 2008, 9, 1924-1933) or in Darensleid et al. (D. J. Darensbourg, W. Choi, P. Ganguly, C. P. Richers Macromolecules, 2006, 39, 4374-4379) or in Helou et al. (M. Helou, O. Miserque, J.- M.
• TMC is a bio-resourced monomer directly derived from glycerol, itself a by-product of the degradation of triglycerides. This molecule, unlike LA, is not issued from the exploitation of resources otherwise used in the food chain as discussed by Zhou et al. (C-H. Zhou, J. N. Beltramini, Y -X. Fan, G. Q. Lu Chem. Soc. Rev. 2008, 37, 527-549) or by Behr et ai. (A. Behr, J. Eilting, K. Irawadi, J. Leschinski, F. Lindner Green Chem. 2008, 10, 13-30).
• the catalyst system was based on zinc, a "bio-metal", which was not associated to potential toxicity issues contrary to tin-based systems.
• Another challenge consists in the incorporation of sizeable amounts of bio-resources in the classical commodity synthetic polymers, namely poly( ⁇ -olefin)s and more particularly poiy(styrene)s.
• the preparation of copolymers of cyclic esters (LA, CL, GL) or carbonates (TMC) with styrene (S) has therefore been investigated for example in European patent application n° 08290732.0, or in Zalusky et al. (A. S. Zalusky, R. Olayo-Valies, J. H. Wolf, M.A. Hillmyer, J. Am. Chem. Soc, 2002, 124, 12761-12773) or in Barakat et ai. (I.
• LA and TMC have been used to prepare copolymers of styrene with physical and mechanical properties related to those of polystyrenes, said copolymers containing up to 50% of the bio-monomer.
• European patent application n° 08290732.0 discloses the immortal polymerisation of large amounts of LA. It was performed in neat styrene with safe metal-based initiators such as (BDl)ZnN(SiMe3) 2 in combination with a bi-functional alcohol such as 4- hydroxy-2,2,6,6-tetramethylpiperidinooxy (TEMPO-OH) or 2-hydroxyethyl- methacrylate (HEMA), to produce end-functionalised polylactides. These PLAs were then employed for the controlled preparation of poly(lactide- ⁇ >/ocfc-styrene)s wherein the length of each block could be tuned at will.
• safe metal-based initiators such as (BDl)ZnN(SiMe3) 2
• a bi-functional alcohol such as 4- hydroxy-2,2,6,6-tetramethylpiperidinooxy (TEMPO-OH) or 2-hydroxyethyl- methacrylate (HEMA)
• the present invention discloses a class of phenol-based pro-iigands of formuia
• R 1 is (CH 2 ) ⁇ NCH 2 CH 2 (OCH 2 CH 2 ),! wherein m is 1 , 2 or 3 and n ⁇ 1);
• R 2 is hydrocarbyl group having 1 to 10 carbon atoms and is preferably selected from methyl, ethy!, iso-propyl, tert-butyl or neo-pentyl;
• R 3 is the same as R 1 or is hydrocarbyl group having 1 to 20 carbon atoms and is preferably alkyi selected from methyl, ethyl, iso-propyl, tert-butyl, neo-pentyl, cumyl, trityl or aryl selected from phenyl, 2,4,6-trimethylphenyl, 2,6- diisopropylphenyl.
• R 1 which must simultaneously comprise a nitrogen function and an oxygen atom engaged in the cycle. It is a cycloazoether.
• the present ligands are particularly stable because of the presence of oxygen in the morpholine or aza-ethers.
• Ligands of the prior art such as for examples those disclosed in Zheng et al. (Z. Zheng, G. Zhao, R. Fablet, M. Bouyahyi, CM. Thomas, T. Roisnel, O. Casagrande, J.-F. Carpentier, in New Journal of Chemistry, 32, 2279, 2008) are less performing than the present ligands as oxygen is not present in the piperazine cycle. They are therefore less stable than the present ligands with respect to the metallic centre. The ligands of the prior art thus decompose more rapidly than the present ligands and their productivity and degree of control on the polymerisation reaction are thereby reduced.
• pro-ligands can be prepared following any method known in the art.
• the present method for preparing the pro-iigands and metal complexes is a modification of the method described in Schanmuga et al. (S. Shanmuga Sundara Raj, M. N. Ponnuswamy, G. Shanmugam, M. Kandaswamy, J. Crystallogr, Sp ⁇ ctrosc. Res., 1993, 23, 607-610) or in Teipel et al. (S. Teipel, K. Griesar, W. Haase, B. Krebs, Inorg. Chem., 1994, 33, 456-464).
• the pro-iigands are then used to prepare complexes of divalent metals of Groups 2 and 12 of the Periodic Tabie.
• the preferred metals are magnesium, calcium, zinc, strontium and barium, preferably magnesium, calcium and zinc.
• the complexes are prepared by reacting the pro-ligand with a precursor M(X) 2 wherein X is either an alky!
• the prefered precursors are ZnEt 2 , Mg(VjBu) 2 , Mg(N(SiMe3)2)2, Ca ⁇ N(SiMe 3 ) 2 ) 2 (THF) 2 .
• the present invention further provides metal complexes of formula [LO]-M-X, wherein
• - M is Zn, Mg, Ca, Sr or Ba.
• - X is hydrocarbyl, or alkoxide group OR" wherein R" is hydrocarbyl, aryl, silyl, or amino group NR* 2 wherein R* is SiMe 3 , iso-propyi, methyl or ethyl.
• the preferred hydrocarbyl is ethyl.
• R 1 , R 2 and R 3 are as described hereabove.
• the present invention discloses a process for polymerising cyclic esters and five- or six- or seven-membered cyclic carbonates by ROP in the presence of a system comprising an alcohol an a divending metal complex supported by chelating phenoxy ligands.
• these metal complexes are very active and productive catalytic systems for the controlled immortal ROP of iactides, cyclic esters and 5- to 7-membered cyclic carbonates.
• the polymerisation can be carried out in solution in an organic solvent or in melt, in the absence of solvent, at temperature ranging from 20 0 C to 200 0 C, preferably from 25 0 C to 110 0 C.
• the conversion of at least 50 000 and up to 500 000 equivalents of monomer preferably 50 000 to 100 000 equivalents, can be achieved in the presence of up to thousands equivalents of alcohol per metal centre.
• the alcohol can be represented by formula R'OH wherein R' is an hydrocarbyl group, linear or branched, having from 1 to 20 carbon atoms.
• R 1 is a primary or secondary alkyl residue or benzylic group, more preferably it is iso-propyl ( 1 Pr) or benzyl (Bn).
• It can also be a poly-ol such as a diol, triol or higher functionality polyhydridic alcohol, typically selected from 1 ,3-propanedioi or trimethylolpropane, possibly derived from biomass such as glycerol or any other sugar-based alcohol such as for example erythritol or a cyclodextrine.
• Ail alcohols can be used individually or in combination.
• the alcohol is selected from iso-propanol, sec-butanoi or benzyi alcohol.
• the polymerisation reaction can be represented by;
• R 1 , R 2 growing polymer chain; [M): organometallic fragment k ir : transfer rate constant; /c p: propagation rate constant
• the alcohol acts as a reversible transfer agent.
• a rapid alkoxide/alcohol exchange takes place. It is observed that, as the ratio alcohol/metal increases, the molecular weight of the polymer chains decreases to the same extent.
• the rate of transfer reaction /c tr is rapid enough relative to the polymerisation rate k p , the molar mass distribution of the macromolecules formed is narrow.
• the molecular weight of the polycarbonate depends upon the nature of the alcohol/polyoL
• functionalised alcohols can be used in combination with the initiators according to the present invention to promote efficiently the immortal ROP of L-LA and rac-LA and TMC in styrene thereby allowing the preparation of end- functionalised polymers.
• the functionalised group can in turn be used for the in sit ⁇ - synthesis of copolymers of LA or TMC and styrene.
• the preferred functionalised alcohols are preferably selected from TEMPO-OH, HEMA or various hydroxy-alkoxyamines such as AA-OH.
• the cyclic esters are selected from L-lactide (L-LA), rac-lactide, (rac-LA), or rao- ⁇ -butyro!actone, (rac-BBL).
• L-LA L-lactide
• rac-LA rac-lactide
• rac-BBL rao- ⁇ -butyro!actone
• the preferred cyclic carbonates are selected from TMC and its substituted derivatives. Non-limitative examples are shown below:
• Polymerisation is conducted at a temperature ranging from 20 0 C to 200 0 C, preferably between 25 and 110 0 C.
• the pressure ranges from 0.5 to 20 atm, preferably it is 1 atm.
• the polymers thus prepared show typically a unimodal molecular weight distribution that ranges from 1.1 to 5.0, more typically from 1.1 to 1.7.
• the number average molecular weight M n can be tuned by the monomer-to-alcohol ratio and ranges from 1 000 to 1 000 000 g/mol, more typically from 10 000 to 250 000 g/mo!.
• the experimental molecular weights, as determined by size exclusion chromatoghraphy, are in excellent agreement with molecular weights calculated from the monomer-to-alcohol ratio and monomer conversion.
• Figure 1 represents the X-ray structure of ligand [LO 2 ]H, wherein hydrogen atoms are omitted for clarity.
• Figure 2 represents the X-ray structure of complex [LO 1 ]ZnEt, wherein hydrogen atoms and benzene moiecules are omitted for ciarity.
• Figure 3 represents the X-ray structure of dimer [LO 1 ]CaN(SiMe 3 )2 wherein hydrogen atoms are omitted for ciarity.
• Figure 5 represents the high resolution MALDI-TOF mass spectrum (main population: Na + ; minor population: K + ) of a low moiecular weight PLLA having a number average molecular weight Mn G pc of 4 700 g/mol, prepared with L-LA/[LO 1 ]ZnEt//PrOH in relative amounts of 1 000/1/10 with a 20% conversion.
• Figure 6 represents the MALDl-TOF mass spectrum (minor population: Na + ; main population: K + ) of a medium molecular weight PLLA having a number average moiecular weight Mn G ⁇ c of 13 200 g/mol, prepared with L-LA/[LO 1 ]ZnEt//PrOH in relative amounts of 2 500/1/25 with a 98% conversion.
• Figure 7 represents the MALDI-TOF mass spectrum (main population, Na + ; minor population, K + ) of a low molecular weight PLLA having a number average molecular weight Mn G pc of 4 600 g/mo! prepared with L-UV[LO 1 ]MgBu//PrOH in relative amounts of 5 000/1/100 with a 71% conversion.
• AIi manipulations were performed under inert atmosphere on the bench using a Schlenk line and standard Schlenk techniques or in a dry, solvent-free glove-box (Jacomex; O 2 ⁇ 1 ppm, H 2 O ⁇ 5 ppm) for catalyst loading.
• ZnEt 2 (1.0 M in hexanes) and MgBu 2 (1.0 M in heptane) were received from Aldrich and transferred to sealed ampoules for storage.
• Benzyl alcohol (>99.0%) was purchased from Aldrich, stored over activated 3 A molecular sieves and subsequently used without further purification.
• iPrOH HPLC grade, VWR
• TEMPO-OH 4-hydroxy-2,2,6,6-tetramethylpiperidinooxy
• Styrene (99+%) was received from Aldrich, dried for several days over CaH 2 , distilled by gentle heating at a temperature of about 45 0 C, under dynamic vacuum and stored at -24 0 C; it was used within two weeks to avoid contamination by polystyrene.
• Toluene was pre-dried over sodium, and systematically distilled under Argon from meited sodium prior to use.
• THF was first pre-dried over sodium hydroxyde and distilled under Argon over CaH 2 , and then freshly distilled a second time under Argon from sodium mirror/benzophenone prior to use.
• Dioxane was distilled from sodium mirror/benzophenone .
• L-Lactide was provided by Total Petrochemicals; rac-lactide (rac-LA, 99%) was received from Acros. Purification of either of these isomers of Iactide (LA) was typically ensured according to a three-step procedure by re- crystallisation from a hot, concentrated /PrOH solution (80 "C), followed by two subsequent re-crystallisations in hot toluene (105 0 C). Where a shorter, less effective purification of L-LA was required, the monomer was simply re-crystallised once from /PrOH.
• TMC Trimethylene carbonate
• NMR spectra were recorded on Bruker AC-200, AC-300 and AM-500 spectrometers. AIi chemicals shifts were determined using residual signals of the deuterated solvents and were calibrated versus SiMe 4 . Assignment of the signals was carried out using 1D ( 1 H, 13 C ⁇ 1 H ⁇ ) and 2D (COSY, HMBC, HMQC) NMR experiments. Coupling constants are given in Hertz.
• Elemental analyses were performed on a Carlo Erba 1108 Elemental Analyser instrument at the London Metropolitan University and were the average of a minimum of two independent measurements.
• GPC Gel Permeation Chromatography
• microstructure of ⁇ oly(lactide) samples was determined by examination of the methine region in the homodecoupled 1 H NMR spectrum of the polymers recorded at room temperature in CDCb on a Bruker AM-50G spectrometer with concentrations in the range 1.0 to 2.0 mg/mL
• MALDI-TOF MS spectra were obtained with a Bruker Daltonic MicroFlex LT, using a nitrogen laser source (337 nm, 3 ns) in linear mode with a positive acceleration voltage of 2OkV.
• Samples were prepared as follow: 1 ⁇ L of a 2:1 mixture of a saturated solution of ⁇ -cyano-4-hydroxycinnamic acid (Bruker Care) in HPLC quality acetonitrile and a 0.1% solution of trifluoroacetic acid in uitrapure water was deposited on the sample plate. After total evaporation, 1 ⁇ L of a 5 to 1Qmg/mL solution of the polymers in HPLC quality THF were deposited.
• Bruker Care Peptide Calibration Standard and Protein Calibration Standard I were used for external calibration.
• [LO 2 ]H is fully soluble in all common organic solvents, including aliphatic hydrocarbons.
• a mixture of 1.03 g of 2,4-di- t buty1-phenol (5.0 mmol), 0.5 ml_ of formaldehyde (37 wt- % in water, 6.2 mmol) and 1.25 g of 1-aza ⁇ 15-crown-5 (5.7 mmol) was refluxed in 20 mL of dioxane for 24 h at a temperature of 120 °C. The solvent was removed under vacuum to yield an orange oil which was dried to constant weight of 2.23 g with a crude yield.
• the compiex is soluble in THF and diethyl ether, but has a limited solubility in toluene and is not soluble in light petroleum ether.
• [LO 1 ]CaN(SiMe 3 ) 2 were grown by slow diffusion of hexane in a THF solution at room temperature, and its solid-state structure was elucidated by X-ray diffraction.
• L-LA (respectively rac-LA)
• PLLA (respectively PLA)
• Table I An overview of Table I indicates that an extremely large number of equiv. of L-LA can be polymerised in a controlled fashion with [LO 1 ]ZnEt in presence of alcohol. Both the polydispersity indexes and the correlation between expected and observed molecular weights remain good to excellent when monomer loading is increased, even for L- LA/[LO 1 ]ZnEt ratios of up to 50 000. Conversions are quantitative, under the conditions employed, for ratios L ⁇ LA/[LO 1 JZnEt ranging between 500 and 50 000.
• Concentrations of monomer in toluene of up to 6.0 M can be used, as the rapid conversion of the monomer facilitates its complete dissolution in the aromatic solvent. At high conversion, ail of the monomer dissolves in the reaction medium, whereas the resulting polymer is not soluble and precipitates at high conversion. The evolution of the reaction can therefore be readily monitored in a visual manner.
• the ROP of LA in coordinating solvents such as THF is slower than in non- coordinating solvents such as toluene, as can be seen by comparing examples 4 (toluene; 97% conv.) and 7 (THF, 57% conv.); this decrease in polymerisation kinetics results from the fact that in coordinating solvents, coordination onto the metal centre by the monomer is impeded by that of the solvent. Nevertheless, the polymerisation in THF remains very well controlled.
• /PrOH proved an extremely efficient chain transfer agent for the immortal, controlled ROP of a large excess of LA with [LO 1 ]ZnEt.
• this methodology is not restricted to /PrOH, and other alcohols can be efficiently used in its place, such as for example benzyl alcohol, TEMPO-OH, HEMA or various hydroxy-alkoxyamines.
• benzyl alcohol, TEMPO-OH, HEMA or various hydroxy-alkoxyamines This is successfully illustrated by examination of examples 4 and 5: kinetics and control of the polymerisation parameters are identical in both cases.
• /PrOH can be substituted adequately for example by AA-OH.
• the immortal ring-opening polymerisation of LA with initiator [LO 2 ]ZnEt in presence of an alcohol as transfer agent is extremely rapid and well-controlled.
• the polymerisation of 1 000 equiv. of L-LA in toluene with 10 equivalents of iPrOH is achieved within 60 min at a temperature of 60 0 C as can be seen in example 17 of Table II.
• Nearly quantitative conversion of 5 000 equiv. of L-LA in toluene with 25 equivalents of iPrOH requires 90 min at a temperature of 60 0 C.
• Magnesium complex [LO 1 JMgBu constitutes a very efficient initiator for the ROP of LA, and, in association with alcohol, promotes the rapid and controlled immortal polymerisation of the cyclic di-ester.
• the polymerisation of 1 000 equivalents of L-LA with 10 equivalents of /PrOH as transfer agent was nearly quantitative as seen in exampie 21 of Table ill: it was completed in 15 min, very well controlled and proceeded without noticeable epimerisation of the stereo-centres as indicated by a P m of 1.00.
• [LO 1 JMgBu was fairly sensitive to both monomer purity and transfer agent loadings.
• increasing the number of equivalents of iPrOH from 25 (example 24) to 100 (example 26) at a fixed L-LA/[LO 1 ]MgBu ratio of 5 000 and with the same reaction time resulted in a slight decrease in activity; this presumably reflects the higher oxophiiicity of Mg-based complexes in comparison with their zinc counterparts. This drop in kinetics could be partly circumvented by increasing the reaction temperature.
• initiator [LO 1 ]CaN(SiMe 3 ) 2 was rather slow in comparison to the other examples carried out in the presence of alcohol.
• polymerisation of up to 2 500 equivalents of L-LA is achieved extremely rapidly at a temperature of 60 0 C.
• quantitative conversion of 500 equivalents of monomer was performed within one minute for ratio /PrOH/ [LO 1 ]CaN(SiM ⁇ 3 ) 2 > 10 as seen in example 33. It took less than 15 min to convert 1 000 equivalents of monomer under the same conditions as shown in examples 35 to 37.
• Polymerisation was well controlled as indicated by polydispersity indexes in the range of 1.20 to 1.40, and by the close agreement between experimental and theoretical molecular weights, even for values of the ratio /PrOH/ [LO 1 ]CaN(SiMe 3 ) 2 of 50. It must be mentioned that a significant broadening of the polydispersity index, which reached up to 1.6-1.7, was observed when the reactions were prolonged after complete conversion of the monomer, related to undesirable trans-esterification processes.
• the catalyst [L0 1 ]CaN(SiMe 3 )2//Pr0H performed very well at low temperatures, both in terms of kinetics and of control. Thus, the conversion of 500 equivalents of monomer reached 70% after 1 minute at room temperature as seen in example 40 whereas it was complete at a temperarure of 60 0 C as shown in example 33.
• THF example 42
• L is ZnEt 2 6 60 78 11 1 300 1 600 1.09
• Examples 43 to 47 performed with a ratio L ⁇ LA/[M]//PrOH of 1 000/1/10 at a temperature of 60 0 C and for a period of time of 15 minutes indicated that complexes [LO 1 JZnEt and [LO 2 JZnEt seemed far less active than the other 3 precursors, and they were ranked as follows in terms of increasing activity: [LO 2 ]ZnEt « [LO 2 JZnEt « (BDI)ZnN(SiMe 3 ) 2 [LO 1 3CaN(SiMe 3 ) 2 ⁇ [LO 1 JMgBu.
• L-LA (respectively rac-LA)
• PLLA (respectively PLA)
• the metallic initiators of the present invention were suitable for the immortal ROP of LA in styrene, as exemplified in Table Vl.
• polymerisation of 1 000 equivalents of L-LA in styrene was completed in less than 15 minutes, well controlled, and proceeded without interference and without polymerisation of styrene. This therefore makes these systems suitable for the large-scale synthesis of terminally functionalised PLLA and subsequent preparation of poly(LA-jb/oc/c-styrene) copolymers.
• TMC trimethviene carbonate
• TMC was polymerised in styrene without any noticeable detrimental effect from the solvent in a controlled, immortal manner with an initiator selected from (BDI)Zn- N(SiMe 3 ) 2 , [LO 1 JZnEt, [LO 2 JZnEt, [LO 1 JMgBu or [LO 1 JCaN(SiMe 3 ) 2 and an alcoho! selected from iPrOH, BnOH 1 AA-OH, HEMA and TEMPO-OH .
• initiator selected from (BDI)Zn- N(SiMe 3 ) 2 , [LO 1 JZnEt, [LO 2 JZnEt, [LO 1 JMgBu or [LO 1 JCaN(SiMe 3 ) 2
• an alcoho! selected from iPrOH, BnOH 1 AA-OH, HEMA and TEMPO-OH .
• Functionalised 6-membered cyclic carbonates were poiymerised in bulk in a controlled, immortal manner with an initiator selected from (BDI)Zn-N(SiMe3)2, [LO 1 ]ZnEt, ELO 2 JZnEt 1 [LO 1 ]MgBu or [LO 1 3CaN(SiMe 3 ) 2 and an alcohoi selected from ⁇ PrOH, BnOH, AA-OH, HEMA and TEMPO-OH, as shown in Table IX. TABLE IX.
• the bulk polymerisation of rac-BBL was efficiently promoted in a controlled, immortal manner with an initiator selected from (BDi)Zn-N (SiMe 3 ) 2 , [LO 1 JZnEt, [LO 2 ]ZnEt, [LO 1 ]MgBu or [LO 1 ]CaN(SiMe 3 ) 2 and an alcohol delected from /PrOH, BnOH, AA-OH, HEMA and TEMPO-OH, as seen in Table X.
• an initiator selected from (BDi)Zn-N (SiMe 3 ) 2 , [LO 1 JZnEt, [LO 2 ]ZnEt, [LO 1 ]MgBu or [LO 1 ]CaN(SiMe 3 ) 2 and an alcohol delected from /PrOH, BnOH, AA-OH, HEMA and TEMPO-OH, as seen in Table X.
• [LO 1 ]ZnEt Upon addition of 10 equivalents of /PrOH, [LO 1 ]ZnEt readily converted 200 to 500 equivalents of rac-BBL within hours in a quantitative fashion.
• the PDi of the resulting polymers were very narrow, typically around 1.10, and the experimental molecular weights (determined by GPC or MALDl-TOF mass spectroscopy) were in excellent agreement with their theoretical values.
• [LO 1 ]ZnEt compared well with prior art (BDi)Zn-N(SiMe 3 ⁇ , both in terms of activity and control, as shown by examples 84 and 85.

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