Classifications

• • 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
  • C08G63/823—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
  • C08G63/64—Polyesters containing both carboxylic ester groups and carbonate groups
• • 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
  • C08G64/18—Block or graft polymers
• • 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
  • C08G64/30—General preparatory processes using carbonates
  • C08G64/302—General preparatory processes using carbonates and cyclic ethers
• • 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
  • C08G81/00—Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers
  • C08G81/02—Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers at least one of the polymers being obtained by reactions involving only carbon-to-carbon unsaturated bonds
  • C08G81/024—Block or graft polymers containing sequences of polymers of C08C or C08F and of polymers of C08G
  • C08G81/027—Block or graft polymers containing sequences of polymers of C08C or C08F and of polymers of C08G containing polyester or polycarbonate sequences
• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
  • C08K5/00—Use of organic ingredients
  • C08K5/04—Oxygen-containing compounds
  • C08K5/05—Alcohols; Metal alcoholates
  • C08K5/053—Polyhydroxylic alcohols
• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
  • C08K5/00—Use of organic ingredients
  • C08K5/36—Sulfur-, selenium-, or tellurium-containing compounds
  • C08K5/41—Compounds containing sulfur bound to oxygen
  • C08K5/42—Sulfonic acids; Derivatives thereof

Definitions

• the invention relates to the field of selective copolymerization of cyclic monomers.
• the invention relates to a method of controlling the structure of a block copolymer synthesized by selective copolymerization, by ring opening, of cyclic monomers of carbonate and lactone.
• polycarbonates in the form of homopolymers or copolymers with other biodegradable polyesters can be used as a drug encapsulant or as biodegradable implants, particularly in orthopedics, to suppress the interventions that were necessary in the past to remove the parts. such as pins for example.
• Such polymers can also be used in coating and plastic formulations.
• Polycaprolactones are also biocompatible and biodegradable. They have good physicochemical properties and good thermal stability up to temperatures of at least 200-250 ° C.
• Organo-catalysts have been developed to allow the ring-opening polymerization of lactones, in particular ⁇ -caprolactone denoted “ ⁇ -CL” in the following description and cyclic carbonates, in particular trimethylene carbonate. noted “TMC” in the following description.
• AMS methanesulfonic acid
• the AMS in combination with a protic initiator, of alcohol type, the AMS is capable of promoting the controlled polymerization of these cyclic monomers of ⁇ -caprolactone and trimethylene carbonate.
• the protic initiator allows fine control of average molar masses as well as chain ends.
• the second population comprises random copolymers consisting of chains with two hydroxyl termini, also called telechelic copolymers.
• This second population of copolymers derives from the competitive propagation mechanism, of the "ACE" type, of the TMC.
• ACE competitive propagation mechanism
• the document describes the use of a diol as a initiator, and more particularly 1,4-phenylene dimethanol.
• the two mechanisms of propagation in competition then give rise to the formation of random telechelic type copolymers, differing only in the central unit.
• the central unit is a phenylene and the polymer chain obtained is derived from the "AM” type propagation mechanism and in the second case, the central unit is a propylene and the polymer chain obtained is derived from the combination of "AM” and "ACE” propagation mechanisms.
• block copolymers based on these two types of monomers.
• the applications envisaged for this type of block copolymer are multiple. They can be related to the fields of surgery and orthopedics for example, because of the biocompatibility of these copolymers.
• Block copolymers can also be used as additives in polymer matrices to improve the impact resistance of a final material.
• the block copolymers have a capacity to nanotructure, that is to say that the arrangement of the constituent blocks of the copolymers is structured, by phase segregation between the blocks thus forming nano-domains. Due to this phase segregation, they can be used as masks in nano-lithography processes to produce products in the field of microelectronics and micro-electro-mechanical systems (MEMS).
• MEMS micro-electro-mechanical systems
• the object of the invention is to propose a process for controlling the structure of a block copolymer by selective ring-opening copolymerization of cyclic carbonate and lactone monomers in the presence of a dicarboxylic acid catalyst. methanesulfonic acid, said process making it possible to obtain a single population of block copolymer, free from contamination by other copolymers or homopolymers, and of a perfectly defined and controlled structure.
• the invention relates to a method for controlling the structure of a block copolymer by selective copolymerization, by ring opening, of cyclic monomers of carbonate and lactone in the presence of a catalyst based on methanesulfonic acid, said process comprising a sequence of steps carried out strictly in the following order:
• the cyclic carbonate is trimethylene carbonate (TMC)
• the lactone is ⁇ -caprolactone ( ⁇ -CL)
• the copolymer obtained is a triblock copolymer of P (CL-b-TMC-b-CL);
• the molar ratio of monomers to initiator, TMC /? -CL / initiator, is between 60/60/1 and 120/240/1;
• AMS initiator / catalyst
• the process is carried out at a temperature of between 20 and 120 ° C., and preferably between 30 and 60 ° C .;
• the non-chlorinated aromatic solvent is chosen from toluene, ethylbenzene or xylene.
• the invention also relates to a PCL-b-PTMC-i-PCL block copolymer obtained according to the control method described above, said block copolymer being characterized in that each of the PCL blocks has a degree of polymerization of between 30 and 120 and a number-average molecular weight Mn of between 3400 and 13680 g / mol and in that the PTMC block has a degree of polymerization of between 60 and 120 and a number-average molecular weight M n between 6100 and 12200 g / mol.
• the term "monomer” as used refers to a molecule that can undergo polymerization.
• polymerization refers to the process of converting a monomer or mixture of monomers into a polymer, the structure of which essentially comprises the multiple repetition of units derived from more than one monomeric molecule. low molecular weight.
• polymer is meant either a copolymer or a homopolymer.
• copolymer means a polymer derived from at least two species of monomers or macromonomers, at least one of which is selected from a lactone and the other from a cyclic carbonate.
• homopolymer a polymer derived from a single species of monomer or macromonomer only.
• block copolymer is understood to mean a polymer comprising one or more uninterrupted sequences of each of the different polymeric species, the polymer blocks being chemically different from one another or from each other and being bound together. by a covalent bond.
• the method for controlling the structure of a block copolymer according to the invention is carried out by selective copolymerization, by ring opening, of cyclic monomers of carbonate and lactone in the presence of an acid-based catalyst. methane.
• the cyclic carbonate monomer is trimethylene carbonate (TMC) and the lactone is ⁇ -caprolactone ( ⁇ -CL).
• TMC trimethylene carbonate
• ⁇ -CL ⁇ -caprolactone
• the block copolymer synthesized according to this control method is advantageously a copolymer PCL-b-PTMC-i -PCL triblocks, whose central block is PTMC, formed during a first phase of the selective copolymerization.
• This selective copolymerization advantageously comprises a sequence of steps performed strictly in a predetermined order.
• a first step consists in dissolving the cyclic carbonate monomer, in particular TMC, in a non-chlorinated aromatic solvent.
• the non-chlorinated aromatic solvent may be selected from toluene, ethylbenzene or xylene. Toluene is however preferred to the other two solvents.
• a second step then consists in adding to the monomer solution TMC, a bifunctional initiator comprising at least 2 hydroxyl functions.
• This initiator may especially be chosen from diols or water.
• the methanesulfonic acid (AMS), acting as a catalyst for the TMC polymerization reaction, is then added to the reaction medium.
• the PTMC polymer thus formed is a telechelic polymer whose structure is completely identical to that of the PTMC polymer formed according to the competitive mechanism, by activated chain end "ACE". As a result, at this stage of the process, a single population of dihydroxy PTMC polymer is obtained.
• a single telechelic polycarbonate is obtained, in particular the dihydroxylated PTMC polymer, present in the reaction medium.
• This polymer can then act, in a second phase of the selective copolymerization process, as a macro-initiator for the polymerization of the lactone, in particular ⁇ -caprolactone, ⁇ -CL.
• Figure 3 This strict sequence of synthesis steps of the block copolymer provides a defined structure free of contamination of homopolymers or other types of block copolymers or statistics.
• the order of addition is reversed (first ⁇ ⁇ -CL and then TMC) the obtained block copolymer is contaminated with PTMC homopolymer.
• the control of the structure is very important because the pollution with other species can disturb the structuring by phase segregation.
• a very important characteristic of block copolymers is the phase segregation of the blocks which separate into nano-domains. This phase segregation depends essentially on two parameters.
• a first parameter called the interaction parameter of Flory-Huggins and noted “ ⁇ ”, makes it possible to control the size of the nano-domains. More particularly, it defines the tendency of blocks of the block copolymer to separate into nano-domains.
• the product ⁇ , the degree of polymerization N, and the Flory-Huggins parameter ⁇ give an indication of the compatibility of two blocks and whether they can separate. For example, a diblock copolymer of strictly symmetrical composition separates into micro-domains if the product ⁇ is greater than 10.49. If this product ⁇ is less than 10.49, the blocks mix and the phase separation is not observed at the observation temperature.
• the degree of polymerization of the blocks must be sufficiently high.
• the concentration of each monomer in the reaction medium may therefore vary to a certain extent.
• the molar ratio in monomers / initiator (TMC / £ -CL / initiator) is preferably between 60/60/1 and 120/240/1. Indeed, a lower ratio, for example 40/40/1, does not allow to observe the segregation of phases.
• PCL blocks are obtained whose number-average molecular weight Mn is between 3400 and 13680 g / mol.
• blocks are obtained for a degree of polymerization of the PTMC between 60 and 120. PTMC whose number-average molecular weight Mn is between 6100 and 12200 g / mol.
• the amount of AMS catalyst used in the process it is possible to vary the amount of AMS catalyst used in the process, to adjust the reaction time without affecting the control of the polymerization.
• the molar ratio of the dihydroxy initiator to the AMS catalyst be of the order of 1. It can however vary between 1/1 and 1/3.
• the catalyst can be easily removed at the end of the reaction by neutralization using a hindered organic base such as diisopropylethylamine (DIEA) or a tertiary amine supported on a polystyrene type resin.
• a hindered organic base such as diisopropylethylamine (DIEA) or a tertiary amine supported on a polystyrene type resin.
• the bi-functional initiator is selected from diols or water.
• the triblock copolymer synthesized with such an initiator has a linear morphology.
• the initiator is in the form of a polyhydroxylated polymer, such as, for example, glycerol, pentaerythritol, dipentaerythritol, trimethylolethane, trimethylolpropane, or sorbitol, it may make it possible to obtain triblock copolymers having a star morphology.
• This process is preferably conducted at a temperature ranging from 20 to 120 ° C and more preferably from 30 to 60 ° C, in particular when the solvent is toluene. It is indeed possible to obtain, at a temperature of the order of 30 ° C., block copolymers of PCL- ⁇ -PTMC-1 -PCL having molecular masses M n greater than 18,000 g / mol in a few hours. and with a yield greater than or equal to 80% after purification.
• This process is further preferably conducted with stirring. It can be implemented continuously or discontinuously.
• the reagents used in this process are preferably dried before use, in particular by vacuum treatment, distillation or drying with an inert desiccant.
• the alcohols were distilled on sodium. Toluene is dried using a MBraun SPS-800 solvent purifier. Trimethylene carbonate TMC was dried in solution of dry tetrahydrofuran (THF) on calcium dihydride (CaH2) and recrystallized 3 times in cold THF. Methanesulfonic acid (AMS) was used without further purification. Diisopropyl ethylamine (DIEA) was dried and distilled on CaH2 and stored on potassium hydroxide (KOH).
• THF dry tetrahydrofuran
• CaH2 calcium dihydride
• DIEA Diisopropyl ethylamine
• KOH potassium hydroxide
• the Schlenk tubes were dried with a vacuum heat gun to remove any trace of moisture.
• the spectra are recorded in deuterated chloroform, on a spectrometer at 500 or 300 MHz according to the examples.
• the number-average molecular weight Mn, by weight Mw, and the degree of polymolecularity (D) of the samples of copolymers taken are measured by steric exclusion chromatography SEC in THF with polystyrene calibration.
• DSC differential scanning calorimetry measurement
• DSC the English acronym "Differential Scanning Calorimetry” is a thermal analysis technique to measure the differences in heat exchange between a sample to be analyzed and a reference during phase transitions.
• a NETZCH DSC204 differential scanning calorimeter was used. The calorimetry analyzes were performed between -80 and 130 ° C and the values of T g and T m were recorded during the second temperature rise (at a rate of 10 ° C / min).
• Example 1 (Comparative) Preparation of a diblock copolymer PCL-ib-PTMC (with introduction of ⁇ -CL first in the reaction medium)
• the trimethylene carbonate TMC (675 mg, 6.6 mmol, 80 equiv.) Is added to the reaction medium and the solution is stirred under argon at 30 °. C for 7h. Excess diisopropylethylamine (DIEA) is then added to neutralize the catalyst, and the solvent is evaporated in vacuo. The polymer obtained is then dissolved in the minimum of dichloromethane, precipitated by addition in cold methanol, filtered and dried under vacuum.
• DIEA diisopropylethylamine
• a copolymer of PCLso-b-PTMCso is obtained with a conversion of greater than 96% and a yield of 90%.
• trimethylene carbonate TMC (25 g, 0.245 mol, 27 equiv) is added to the reaction medium and the solution is stirred under argon at 30 °. C for 2.5h. Excess diisopropylethylamine (DIEA) is then added to neutralize the catalyst, and the solvent is evaporated in vacuo. The polymer obtained is then dissolved in the minimum of dichloromethane, precipitated by addition in cold methanol, filtered and dried under vacuum.
• DIEA diisopropylethylamine
• a PTMC-ib-PCL-b-PTMC copolymer is obtained with a conversion of greater than 96% and a yield of 85%.
• the integration of the signal corresponding to the -CH 2 OH termination of the PTMC block is greater than 4, indicating the presence of polymer chains other than those initiated by the polycaprolactone dihydroxylated HO-PCL-OH. That means therefore the synthesized triblock copolymer of PTMC-b-PCL-i-PTT TM is not alone but mixed with another telechelic type PTMC homopolymer.
• Example 3 Preparation of a PCL- ⁇ ) -PTMC- ⁇ -PCL Triblock Copolymer with a ⁇ -CL / TMC 2/1 Ratio
• DIEA diisopropylethylamine
• triplet signal at 3.74 ppm indicates that all the polymer chains have CH 2 OH ends of a caprolactone unit (t signal at 3.64 ppm). This confirms the absence of telechelic PTMC homopolymer.
• the two identified glass transition temperatures Tg1 and Tg2 are close to the glass transition temperatures of each PCL and PTMC homopolymer respectively, indicating the observation of a phase segregation between the blocks.
• Example 4 Preparation of a triblock copolymer PCL- ⁇ -PTMC- ⁇ -PCL with a ⁇ -CL / TMC ratio 1/1
• triplet signal at 3.74 ppm indicates that all the polymer chains have CH 2 OH ends of a caprolactone unit (t signal at 3.64 ppm). This confirms the absence of telechelic PTMC homopolymer.
• Tg observed (-28.9 ° C) is close to the glass transition temperature of the PTMC homopolymer, indicating the observation of a phase segregation between PTMC and PCL blocks.
• the size and semi-crystalline nature of the PCL block makes it difficult to observe the Tg1 corresponding to this block.
• Example 5 Preparation of a triblock copolymer PCL-fc-PTMC-i-PCL with a ratio ⁇ -CL / TMC 1/2
• triplet signal at 3.74 ppm indicates that all the polymer chains have CH 2 OH ends of a caprolactone unit (t signal at 3.64 ppm). This confirms the absence of telechelic PTMC homopolymer.
• Tg observed (-22.5 ° C) is close to the glass transition temperature of the PTMC homopolymer, indicating the observation of a phase segregation between PTMC and PCL blocks.
• the size and semi-crystalline nature of the PCL block makes it difficult to observe the Tg1 corresponding to this block.

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• 2015
  • 2015-12-04 FR FR1561864A patent/FR3044668B1/fr not_active Expired - Fee Related
• 2016
  • 2016-11-29 CN CN201680070917.6A patent/CN108291015A/zh active Pending
  • 2016-11-29 SG SG11201804717SA patent/SG11201804717SA/en unknown
  • 2016-11-29 EP EP16819339.9A patent/EP3383934A1/fr not_active Withdrawn
  • 2016-11-29 WO PCT/FR2016/053135 patent/WO2017093652A1/fr active Application Filing
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