Method for synthesising a polyester from polyols

Abstract

The present invention relates to a method for synthesising a polymer of a polyol, preferably glycerol, and polycarboxylate units, preferably a diester of a dicarboxylic acid, in particular sebacate units, in particular PGS comprising the addition of a heterogeneous basic catalyst. The invention also relates to a polymer obtainable by the method. The invention also relates to a polyester of a polyol and a diester of a dicarboxylic acid, having high average molar mass and a controlled degree of branching, and being free from metal traces.

Description

[0001] DESCRIPTION

[0002] TITLE: Process for synthesizing a polyester from polyols.

[0003] FIELD OF THE INVENTION

[0004] The field of the present invention is that of the synthesis of aliphatic polyesters, in particular glycerol polyesters, obtained by transesterification of hydroxyl groups of a polyol and carboxyl groups of a diester by a polycondensation reaction.

[0005] STATE OF THE ART

[0006] Polyesters are widely used to prepare biomaterials used in particular in biomedical applications as materials for polymeric frameworks, for encapsulation of biomolecules or even for surface coating. In particular, among the biocompatible aliphatic polyesters, polymers of glycerol and a diacid are used in the medical field for their biodegradable properties such as for tissue engineering, drug delivery, implants, controlled release of substances, etc.

[0007] A conventional method for synthesizing a polymer of glycerol and a diacid is carried out in a molten medium at high temperature with long reaction times and consists of an esterification step followed by a polycondensation carried out at very low pressure. Such a process is for example described in application EP1448656A1 or application US9359472B2 in the presence of water. A notable problem with these processes is the long reaction time. They require 24 to 48 hours in order to eliminate the water formed during the reaction, and lead to polymers with structural and physicochemical properties that do not always meet application needs. The reduced miscibility of glycerol and sebacic acid requires a high reaction temperature in order to exceed the melting point of sebacic acid, allowing progressive homogenization of the reaction medium.The main consequences are the production of polymers with a high molecular weight distribution (D) and incomplete conversion of monomers after long reaction times, because water, a co-product of the reaction, is difficult to completely eliminate, even after long heating at very low pressure.

[0008] Examples include the presence of water, significant amounts of residual dicarboxylic acid monomers, the presence of carboxylic acid chain ends on the polymer, or acid catalytic residues if an acid catalyst (Lewis or Bronsted) is used during the reaction. This amount of acid functions can be measured by the acid number, expressed in mg of KOH / g of polymer, a technique known to those skilled in the art. These impurities and these functions have a significant impact on the application, particularly when the polymer is used as a raw material for the preparation of crosslinked compositions possibly comprising active ingredients.

[0009] Three problems can thus be highlighted: acid functions, particularly linked to free diacid monomers, can lead to premature acidification of the surrounding environment when the polymer is put into aqueous solution, which can lead to a reduction in biocompatibility resulting in cytotoxicity; acid functions can be incompatible with subsequent chemical modifications of the polymer, for example in the case of functionalization or crosslinking. It can lead to a loss of selectivity in these subsequent reactions and also a degradation of the physicochemical properties of the polymer finally obtained; the free residual water present in the PGS obtained by the acid route, typically measured between 0.10% and 2% by mass, is incompatible with subsequent chemical modifications of the polymer, for example in the case of functionalization or crosslinking.It can lead to a loss of selectivity in these subsequent reactions and also to a degradation of the physicochemical properties of the polymer finally obtained.

[0010] TECHNICAL PROBLEM

[0011] The technical problem that the present invention seeks to solve is to provide an efficient and less energy-intensive process for the synthesis of a polyol polymer, preferably glycerol, and polycarboxylate units, preferably dicarboxylic acid diester, in particular sebacate units, in particular PGS, which meets all the constraints defined above and which overcomes the problems encountered with the prior processes. In particular, the objective of the invention is to provide an efficient and less energy-intensive process for the synthesis of a polyol polymer, preferably glycerol, and polycarboxylate units, preferably dicarboxylic acid diester, in particular sebacate units, in particular PGS, with reduced reaction times, compatible with industrial application and in a non-toxic environment. DISCLOSURE OF THE INVENTION

[0012] Continuing its efforts, the Applicant has developed a process for the synthesis of a polyol polymer, preferably glycerol and polycarboxylate units, preferably dicarboxylic acid diester, in particular sebacate units, in particular PGS, which is efficient, less energy-intensive and significantly faster and which overcomes the synthesis difficulties described above and which provides a non-toxic environment.In particular, the Applicant has developed a synthesis process which makes it possible to obtain a polymer of polyol, preferably glycerol and polycarboxylate units, preferably of dicarboxylic acid diester, in particular of sebacate units, in particular PGS, having a quantity of water equal to zero or very close to zero at the polymerization outlet, an acid number equal to zero or very close to zero and comprising neither residual dicarboxylic acid monomers, nor residual carboxylic acid chain ends, nor acid catalytic residues. The polymer also does not contain traces of transition metal, poor metal or rare earth, in particular tin (Sn). Thus, the polymer obtained is compatible with a biological environment and compatible with various subsequent chemical modifications of the polymer.The process of the invention uses a basic catalyst that is non-toxic, non-carcinogenic, non-mutagenic, non-reprotoxic and separable from the medium by a separation process such as filtration or centrifugation. The reaction to obtain the polymer is a transesterification reaction, which releases an alcohol, preferably methanol, which is easier to eliminate from the medium than water.

[0013] Thus, a first object of the invention is a process for synthesizing a polyester from a polyol and a dicarboxylic acid diester comprising the following steps:

[0014] (a) contacting the polyol monomers, preferably glycerol, and the dicarboxylic acid diester, with a polyol:dicarboxylic acid diester molar ratio ranging from 0.5:1 to 10:1;

[0015] (b) transesterification under an inert atmosphere at a temperature above 25°C;

[0016] (c) placing the reaction medium obtained following step (b) under vacuum, preferably at a pressure less than or equal to 100 mbara (10000 Pa);

[0017] (d) vacuum polycondensation, preferably at a pressure identical to or lower than that of step (c), at a temperature above 25°C; said process comprising the introduction of a heterogeneous basic catalyst selected from the group consisting of CaO, SrO, BaO, and mixtures thereof.

[0018] A second subject of the invention is a polyester capable of being obtained by the process according to the invention. A third subject of the invention is a polyester of polyol and of dicarboxylic acid diester having a number-average molar mass Mn greater than or equal to 2500 g / mol, preferably 3000 g / mol, and an acid number of less than 2 mg KOH / g of polymer.

[0019] SUMMARY OF THE INVENTION

[0020] The invention, described in more detail below, relates to at least one of the embodiments listed in the following points.

[0021] 1. Process for the synthesis of a polyester from a polyol and a dicarboxylic acid diester comprising the following steps:

[0022] (a) contacting the polyol monomers, preferably glycerol, and the dicarboxylic acid diester, with a polyol:dicarboxylic acid diester molar ratio ranging from 0.5:1 to 10:1;

[0023] (b) transesterification under an inert atmosphere at a temperature above 25°C;

[0024] (c) placing the reaction medium obtained following step (b) under vacuum, preferably at a pressure less than or equal to 100 mbara (10000 Pa);

[0025] (d) vacuum polycondensation, preferably at a pressure identical to or lower than that of step (c), at a temperature above 25°C; said process comprising the introduction of a heterogeneous basic catalyst selected from the group consisting of CaO, SrO, BaO, and mixtures thereof.

[0026] 2. Method according to embodiment 1, characterized in that the molar ratio polyol:dicarboxylic acid diester varies from 0.9:1 to 2:1, preferably from 1:1 to 1.5:1.

[0027] 3. Process according to embodiment 1 or 2, characterized in that the dicarboxylic acid diester is a compound of the following formula (I):

[0028] ROOC-(CH2) n-COOR' (I) in which R and R' independently represent a linear or branched alkyl chain, or a vinyl function, and n represents an integer ranging from 1 to 30, preferably ranging from 1 to 10, preferably the dicarboxylic acid diester is chosen from the group consisting of malonic acid diesters, succinic acid diesters, glutaric acid diesters, adipic acid diesters, pimelic acid diesters, suberic acid diesters, azelaic acid diesters, sebacic acid diesters and mixtures thereof, more preferably dimethyl malonate, dimethyl succinate, dimethyl glutarate, dimethyl adipate, dimethyl pimelate, dimethyl suberate, dimethyl azelate, dimethyl sebacate dimethyl, and mixtures thereof, even more preferably the dicarboxylic acid diester is dimethyl sebacate.

[0029] 4. Method according to any one of embodiments 1 to 3, characterized in that step (b) is carried out at a temperature below 200°C, preferably at a temperature varying from 65°C to 200°C, preferably from 120°C to 180°C.

[0030] 5. Method according to any one of embodiments 1 to 4, characterized in that step (b) is carried out for a duration varying from 0.25 h to 10 h, preferably from 1 h to 5 h.

[0031] 6. Method according to any one of embodiments 1 to 5, characterized in that step (d) is carried out at a temperature below 250°C, preferably at a temperature varying from 65°C to 250°C, preferably from 80°C to 200°C, more preferably from 100°C to 180°C.

[0032] 7. Method according to any one of embodiments 1 to 6, characterized in that step (d) is carried out for a duration varying from 0.1 h to 12 h, preferably from 0.5 h to 4 h.

[0033] 8. Process according to any one of embodiments 1 to 7, characterized in that the introduction of the heterogeneous basic catalyst is carried out at a stage chosen from: during stage (b), at the end of the transesterification of stage (b), before the evacuation of stage (c) or after the evacuation of stage (c), preferably during stage (b) during the rise in temperature towards the reaction temperature.

[0034] 9. Process according to any one of embodiments 1 to 8, characterized in that the catalyst is introduced in an amount ranging from 0.01% to 5% by weight, relative to the total weight of polyol monomers and dicarboxylic acid diester, preferably from 0.02% to 3% by weight, more preferably from 0.05% to 1% by weight.

[0035] 10. Method according to any one of embodiments 1 to 9, characterized in that the polycondensation step (d) further comprises removal of the alcohol produced by the polycondensation reaction, preferably by distillation.

[0036] 11. Method according to any one of embodiments 1 to 10, characterized in that the method further comprises a step (e) carried out after step (d), said step (e) being a step of recovering the catalyst, preferably by filtration.

[0037] 12. Polyester obtainable by the process according to any one of embodiments 1 to 11. 13. Polyester of polyol and of dicarboxylic acid diester, preferably poly(glycerol sebacate), having a number-average molar mass Mn greater than or equal to 2500 g / mol, preferably 3000 g / mol, and an acid number of less than 2 mg KOH / g of polymer.

[0038] 14. Polyester according to embodiment 13 further having one or more of the following characteristics, preferably all of the following characteristics: a residual monomer content of less than 5% by weight relative to the total weight of the polymer, a water content of less than 0.3% by weight relative to the total weight of the polymer, a Ca, Sr or Ba metal residue content of less than 1%, preferably less than 0.5%, preferably less than 0.01% by weight of the polymer, a (1,2,3-triacylglyceride) unit content ranging from 10 to 20 mol% relative to all the acylglyceride units of the polymer, a dispersity D of less than 18, a transition metal content of less than 0.05% by weight relative to the total weight of the polymer, a Sc or Bi metal residue content of less than 0.5% by weight of the polymer.

[0039] 15. Polyester according to embodiment 13 or 14, having the following characteristics: a level of Ca, Sr or Ba metal residues of less than 0.01% by weight of the polymer, a level of transition metals of less than 0.05% by weight relative to the total weight of the polymer, a level of Sc or Bi metal residues of less than 0.1% by weight of the polymer, and an acid number of less than 0.4 mg KOH / g of polymer.

[0040] DEFINITIONS

[0041] In this document, unless expressly stated otherwise, all percentages (%) indicated are percentages (%) in moles.

[0042] In this document, unless otherwise indicated, pressure is expressed in absolute pressure indicated by the unit "bara" which corresponds to "absolute bar".

[0043] On the other hand, any interval of values ​​designated by the expression "between a and b" represents the range of values ​​from more than a to less than b (i.e., excluding the limits a and b), while any interval of values ​​designated by the expression "from a to b" means the range of values ​​from a to b (i.e., including the strict limits a and b). In this document, when an interval of values ​​is designated by the expression "from a to b", the interval represented by the expression "between a and b" is also and preferably designated.

[0044] When a "majority" compound is referred to, within the meaning of the present invention, this compound is the majority among the compounds of the same type in the composition, i.e. it is the one that represents the largest quantity by mass among the compounds of the same type. On the contrary, a "minority" compound is a compound that does not represent the largest mass fraction among the compounds of the same type. Preferably, by majority, we mean a mass proportion of more than 50%; when the compound represents 100% by mass, it is also referred to as "majority".

[0045] The compounds mentioned in the description may be of fossil or bio-sourced origin. In the latter case, they may be, partially or totally, derived from biomass or obtained from renewable raw materials derived from biomass. Similarly, the compounds mentioned may also come from the recycling of materials already in use, that is to say, they may be, partially or totally, derived from a recycling process, or obtained from raw materials themselves derived from a recycling process. This particularly concerns monomers.

[0046] For the purposes of the present invention, the term “a” or “an”, as in the expression “a chain” or “an atom” for example, means “one or more” or “at least one”.

[0047] DETAILED DESCRIPTION OF THE INVENTION

[0048] The process according to the invention for preparing a polyester from a polyol, preferably glycerol, and a dicarboxylic acid diester comprises steps (a), (b), (c) and (d) as presented above in embodiment 1.

[0049] Steps (a) and (b) / monomers

[0050] According to step (a) of the process of the invention, the polyol monomers, preferably glycerol and dicarboxylic acid diester are brought into contact.

[0051] The dicarboxylic acid diester monomer according to the invention may be aliphatic, aromatic, or aliphatic / aromatic. In the latter case, the dicarboxylic acid diester comprises an aliphatic part and an aromatic part. It preferably comprises from 3 to 36 carbon atoms. Aliphatic means linear, cyclic or branched aliphatic, whether saturated or unsaturated. According to preferred variants of the invention, the dicarboxylic acid diester monomer is aliphatic and comprises 3 to 36 carbon atoms.

[0052] According to these variants, the dicarboxylic acid diester monomer can preferably correspond to the following formula (I): ROOC-(CH2) n -COOR', in which n represents an integer ranging from 1 to 30, preferably a number ranging from 1 to 10 and R and R' represent, independently of each other, a linear or branched alkyl chain, or a vinyl function.

[0053] Preferably, according to these variants of the invention, the dicarboxylic acid diester monomer may be chosen from diesters corresponding to malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid or a mixture of two or more of these dicarboxylic acid diesters, more preferably the dicarboxylic acid diester is chosen from the group consisting of dimethyl malonate, dimethyl succinate, dimethyl glutarate, dimethyl adipate, dimethyl pimelate, dimethyl suberate, dimethyl azelate, dimethyl sebacate, and mixtures thereof. According to variants of the invention, the dicarboxylic acid diester monomer may be a mixture of at least two different dicarboxylic acid diesters. Preferably then, the dicarboxylic acid diester monomer comprises dimethyl sebacate.

[0054] According to preferred variants of the invention, the dicarboxylic acid diester monomer is dimethyl sebacate.

[0055] According to preferred variants of the invention, the dicarboxylic acid diester monomer and glycerol are the only monomers. Very preferably then, the dimethyl sebacate monomer and glycerol are the only monomers.

[0056] According to any of the variants of the invention, the contacting of the monomers is carried out in a container or reactor. The following reactions can take place in the same reactor. Given the heating and pressure conditions, a person skilled in the art will know how to adapt the type of container or reactor necessary for the process.

[0057] The dicarboxylic acid diester monomer can be used in liquid form or in solid form, preferably in liquid form at room temperature or slightly above room temperature. According to the invention, the contacting of the monomers is advantageously carried out at a temperature below 100°C, preferably below 50°C. Advantageously, the dicarboxylic acid diester monomers have a significantly lower melting point than their corresponding dicarboxylic acids, which facilitates the contacting of the monomers. When the dicarboxylic acid diester monomer is introduced in solid form, the contacting of the monomers is followed by a step of melting the diester monomer, in order to homogenize the medium. Alternatively, the addition of an organic solvent to the monomer mixture allows homogenization of the mixture and thus reduces its overall viscosity.In order to promote this homogenization, agitation is put in place in a known manner.

[0058] Thus, according to variants of the invention, the contacting of the monomers of step (a) is carried out in the presence of an organic solvent, preferably in the presence of a polar organic solvent.

[0059] According to these variants, an organic solvent, more preferably polar and aprotic, is optionally added to the monomers in a quantity by mass of between 0% by mass and 1000% by mass of the mass of the monomers involved, preferably ranging from 5% by mass to 500% by mass of the mass of the monomers involved, more preferably ranging from 10% by mass to 50% by mass of the mass of the monomers involved.

[0060] In the case where the solvent is a polar organic solvent, it is preferably aprotic, chosen by a person skilled in the art as allowing the monomers and the polymer produced to be solubilized and with a boiling point high enough to carry out the reaction under the required conditions, such as for example tetrahydrofuran, dichloromethane, acetone, acetonitrile, trifluorotoluene, diphenyl ether.

[0061] According to an advantageous implementation of the invention, after bringing the monomers of step (a) into contact, the reaction medium is brought to reflux by heating it. The reflux of the medium allows, for example, the melting of the dicarboxylic acid diester monomer when it is introduced in solid form, by bringing it to a temperature ranging from 25°C to 200°C. During this temperature increase step, which makes it possible to obtain a homogeneous medium, care is taken to condense the vapors in the reactor, for example by configuring the column in total reflux, according to methods well known to those skilled in the art. This step is optional if the dicarboxylic acid diester monomer is introduced in liquid form.The polyol monomers and dicarboxylic acid diester react with each other according to the transesterification step (b) of the process of the invention, under an inert atmosphere at a temperature above 25°C, advantageously below 200°C, preferably ranging from 65°C to 200°C, more preferably from 120°C to 180°C, by applying an isotherm or by applying a temperature ramp ranging from +0.1°C / min to +1°C / min in one go or in several ramps interspersed with periods of temperature maintenance until the target temperature is reached. The transesterification reaction time is defined until the conversion to monomers is greater than 70%, preferably greater than 80%, more preferably greater than 90%, i.e. typically ranging from 0.25 h to 10 h depending on the conditions applied, preferably from 1 h to 5 h. Conversion is determined by measuring the mass of distillate produced (alcohol, preferably methanol), or by NMR.13 C by measuring the free polyol or by SEC by measuring the free dicarboxylic acid diester or the free polyol, preferably the free polyol and the dicarboxylic acid diester are respectively glycerol and dimethyl sebacate. These different measurement methods are explained in the section reserved for examples.

[0062] Catalyst

[0063] The catalyst is chosen from barium oxide (BaO), strontium oxide (SrO) and calcium oxide (CaO), alone or in mixtures. The catalyst can be grafted, co-precipitated and shaped using different techniques (doping with an alkali or other element (Li for example) to increase the basic character for example, grafted onto an alumina support for example, calcination under conditions known to those skilled in the art at high temperature under an inert gas flow). These catalysts are solid (heterogeneous).

[0064] The catalyst may be used in the process of the invention in an amount ranging from 0.01% to 5% by weight, relative to the total weight of polyol monomers and dicarboxylic acid diester, preferably from 0.02% to 3% by weight, more preferably from 0.05% to 1% by weight.

[0065] The introduction of the catalyst into the process can be carried out at any stage of the process up to the start of stage (d). Thus, it can be introduced at the start of stage (b), preferably during the temperature rise towards the reaction temperature or when the reaction medium has reached the reaction temperature greater than or equal to 25°C and the medium is homogeneous. Indeed, the catalyst is preferably introduced once the medium is homogeneous. The introduction of the catalyst can also be done directly during stage (b) or at the end of stage (b) before reducing the pressure to an intermediate pressure, or during the reduction, for example upon reaching a plateau, or just before the evacuation of stage (c), or even after the evacuation of stage (c).

[0066] According to a preferred variant, the introduction of the catalyst is carried out at a stage chosen from: during stage (b), at the end of the transesterification of stage (b), before the evacuation of stage (c) or after the evacuation of stage (c), preferably during stage (b) during the rise in temperature towards the reaction temperature.

[0067] These basic catalysts have several advantages over the state of the art:

[0068] These basic catalysts are selective with respect to the desired reaction (transesterification) generating weakly branched chains with a significantly increased molar mass compared to those obtained without using a catalyst, by limiting the parasitic chemistry (etherification and degradation of the polyol, for example glycerol) in the processes described in the state of the art where the reaction media contain acidic species (synthesis of PGS by acid route: presence of carboxylic acids and / or chemistry by acid catalyst (in transesterification or in esterification)). This better selectivity makes it possible in particular to carry out the reaction according to the invention in steps b) and c) at higher temperatures than in the processes described in the state of the art.

[0069] These catalysts are compounds with an acceptable toxicological profile in terms of CMR compounds (carcinogenic, mutagenic, toxic for reproduction). These catalysts are also heterogeneous catalysts which can be removed from the medium at the end of the reaction and then regenerated and recycled by a separation process such as filtration or centrifugation, after optionally a step of diluting the medium in an organic solvent which will also be recycled in the process.

[0070] The catalyst is introduced in solid form. The catalyst can be mixed with the reaction medium in a known manner, for example with stirring.

[0071] Step (c)

[0072] At the end of step (b), the process continues with a step (c) by which the reaction medium is placed under vacuum. Here, the term "vacuum" means the fact of lowering the pressure until it reaches a value less than or equal to 100 mbara, preferably less than 50 mbara, more preferably less than 10 mbara. According to one embodiment, the pressure is within a range from 5 mbara to 50 mbara, preferably from 5 mbara to 10 mbara.

[0073] At the end of step (b), prior to the vacuuming of step (c), the pressure can be gradually reduced, possibly in stages, to an intermediate pressure between atmospheric pressure and vacuum. Any method known to those skilled in the art can be used to lower the pressure according to a ramp or manually, in particular using a diaphragm pump, a rotary pump, etc. Such an intermediate pressure is less than 1 bara and varies, for example, from 800 mbara to 200 mbara.

[0074] Step (d)

[0075] At the end of step (c) and the introduction of the catalyst into the reaction medium, the process of the invention continues with a step (d) of polycondensation at a temperature above 25°C, preferably at a temperature below 250°C, preferably ranging from 65°C to 250°C, more preferably from 80°C to 200°C, more preferably from 100°C to 180°C, optionally following a ramp ranging from +0.1°C / min to 1°C / min. Once the target temperature is reached, the pressure is gradually decreased as close to vacuum. The pressure of step (d) is preferably identical to or lower than that of step (c). According to one embodiment, the pressure of step (d) is less than 50 mbara, more preferably less than 10 mbara. According to one embodiment, the pressure is within a range from 5 mbara to 50 mbara, preferably from 5 mbara to 10 mbara.

[0076] Polycondensation can be carried out instantly in the time required to establish the vacuum at the end of step (b), or for a period of up to 12 hours, preferably up to 6 hours, preferably up to 4 hours.

[0077] According to any of the variants of the invention, the end of the polycondensation is determined by means of the torque of the stirring motor which reaches a target value guaranteeing a targeted molar mass via a targeted viscosity index and / or by SEC (Size Exclusion Chromatography) measurement of a sample taken. The polycondensation duration is for example from 0.1 h to 12 h, or even from 0.5 h to 4 h.

[0078] According to advantageous variants of the invention, concomitantly with step (d), the alcohol, preferably methanol, produced by the polycondensation reaction is removed, for example, by distillation or any other known method for removing alcohol. According to advantageous variants of the invention, concomitantly with step (b) and step (d), the alcohol produced by the transesterification and polycondensation reactions is removed, for example, by distillation or any other known method for removing alcohol or water. When the alcohol is removed by distillation, this may occur in conjunction with stirring and / or purging the contents of the container by reaction under an inert gas.

[0079] End of process

[0080] Steps (a) to (d) of the process according to the invention make it possible to obtain the polyester after a cumulative reaction time of less than 12 h, preferably less than 10 h, preferably less than 8 h.

[0081] According to preferred variants of the invention, the process further comprises a step (e) which is carried out after step (d), said step (e) being a step of recovering the catalyst, preferably by filtration.

[0082] At the end of these steps of the process according to the invention, the polyester produced can be recovered in a known manner, stored if necessary, and possibly treated for subsequent use by techniques known to those skilled in the art.

[0083] Polyester of polyol and diester of dicarboxylic acid

[0084] A second subject of the invention relates to a polyester capable of being obtained by the process according to the invention described above.

[0085] A third subject of the invention is a polyester of polyol and dicarboxylic acid diester having a number-average molar mass Mn greater than or equal to 2500 g / mol, preferably 3000 g / mol, and an acid number of less than 2 mg KOH / g of polymer.

[0086] According to a preferred embodiment, the polyester of polyol and dicarboxylic acid diester further has one or more of the following characteristics, preferably all of the following characteristics: a residual monomer content of less than 5% by weight relative to the total weight of the polymer, a water content of less than 0.3% by weight relative to the total weight of the polymer, a content of Ca, Sr or Ba metal residues of less than 1%, preferably less than 0.5%, preferably less than 0.01% by weight of the polymer, a content of (1,2,3-triacylglyceride) units ranging from 10 to 20 mol% relative to all the acylglyceride units of the polymer, a dispersity D of less than 18, a transition metal content of less than 0.05% by weight relative to the total weight of the polymer, a content of Sc or Bi metal residues of less than 0.5% by weight of the polymer.

[0087] According to advantageous variants of the invention, the polyester has the following characteristics: a level of Ca, Sr or Ba metal residues of less than 0.01% by weight of the polymer, a level of transition metals of less than 0.05% by weight relative to the total weight of the polymer, a level of Sc or Bi metal residues of less than 0.1% by weight of the polymer, and an acid number of less than 0.4 mg KOH / g of polymer.

[0088] The level of residual monomers may be less than 4% by weight relative to the total weight of the polymer, preferably 3% by weight.

[0089] The water content may be less than 0.2% by weight relative to the total weight of the polymer, preferably 0.1% by weight, more preferably 0.05% by weight. The water content corresponds to the quantity of water present in the polymer at the end of its synthesis. Indeed, the polymer obtained can recharge with water during its storage in an atmosphere which is not controlled.

[0090] The acid number may be less than 1 mg KOH / g of polymer, preferably less than 0.5 mg KOH / g of polymer, more preferably less than 0.4 mg KOH / g of polymer, even more preferably less than 0.1 mg KOH / g of polymer.

[0091] The level of metallic residues Ca, Sr or Ba may be less than 0.005% by weight of the polymer, preferably less than 0.001% by weight of the polymer.

[0092] The level of (1,2,3-triacylglyceride) units may be less than 20 mol% relative to all the acylglyceride units of the polymer, preferably this level is 10 to 20 mol% relative to all the acylglyceride units of the polymer when the number-average molar mass Mn is greater than or equal to 2500 g / mol. By "all the acylglyceride units" is meant all the mono-, di- and tri-substituted glycerol monomeric units. The dispersity D may be less than 18, preferably less than 15.

[0093] The level of transition metals may be less than 0.05% by weight relative to the total weight of the polymer, preferably 0.01% by weight of the polymer, preferably less than 0.005% by weight of the polymer, more preferably less than 0.001% by weight of the polymer.

[0094] The level of metallic residues Sc or Bi may be less than 0.1% by weight of the polymer, preferably less than 0.05%, more preferably less than 0.01%, even more preferably less than 0.001% by weight of the polymer.

[0095] According to a particularly preferred variant, the polyester of polyol and dicarboxylic acid diester is poly(glycerol sebacate).

[0096] The physicochemical characteristics of the polyester obtained with the process of the invention suggest interesting homogeneous and reproducible properties, due to the low level of residual monomers, and in particular improved processing properties due to the controlled level of (1,2,3-triacylglyceride) units and therefore the control of the branching level. Indeed, the branching level is expressed as the molar ratio of the level of (1,2,3-triacylglyceride) units to the sum of the levels of all the acylglyceride functions of the polymer. One of the advantages of the process according to the invention is that it makes it possible to obtain polymers with long chains (Mn greater than 2500 g / mol) while having a controlled structure: low dispersity, controlled branching level and low level of residual monomers.

[0097] The residual monomer content is determined according to the method described in the examples.

[0098] The macrostructure (Mn, Mw) of the polyester of glycerol and a dicarboxylic acid diester is determined by SEC according to the method described in the examples.

[0099] The microstructure of the polyester of glycerol and a dicarboxylic acid diester is determined by NMR 13 C according to the method described in the examples.

[0100] The acid number is determined according to the method described in the examples.

[0101] The water content is determined according to the method described in the examples.

[0102] The elemental dosage of metallic elements is determined according to the method described in the examples. The rate of units (1,2,3-triacylglyceride) is determined according to the method described in the examples.

[0103] The above-mentioned characteristics of the present invention, as well as others, will be better understood upon reading the following description of several exemplary embodiments of the invention, given for illustrative and non-limiting purposes.

[0104] EXAMPLES OF CARRYING OUT THE INVENTION

[0105] 1. Measurement methods used to characterize the polymer

[0106] 1.1 Determination of the microstructure of PGS polymers

[0107] The microstructure of polymers is determined by NMR analysis 1 H, supplemented by NMR analysis 13 C when the resolution of the NMR spectra of the 1 H does not allow the assignment and quantification of all species. Measurements are carried out using a BROKER 500 MHz NMR spectrometer at frequencies of 500.43 MHz for proton observation and 125.83 MHz for carbon observation.

[0108] 1.2 Determination of the macrostructure of PGS polymers and residual monomer levels

[0109] The SEC (Size Exclusion Chromatography) technique separates macromolecules in solution according to their size through columns filled with a porous gel. The macromolecules are separated according to their hydrodynamic volume, with the largest being eluted first.

[0110] Although not an absolute method, SEC allows us to understand the distribution of molar masses of a polymer. From commercial standard products, the different number-average (Mn) and weight-average (Mw) molar masses can be determined.

[0111] Size exclusion chromatography analyses were performed using a Viscotek apparatus (Malvern Instruments) equipped with 4 columns, a guard column, and 3 detectors (differential refractometer and viscometer, and light scattering). Samples were dissolved at a concentration of 1 mg.mL' 1 in unstabilized THF, then stirred for 2 hours before being injected.

[0112] 1 mL of a sample solution was filtered through a 0.45 μm PTFE membrane. 100 pL of this solution was eluted in THF using a flow rate of 1 mL.min' 1 at a temperature of 35 °C. OmniSEC software was used for data acquisition and analysis.

[0113] The technique used is size exclusion chromatography (SEC) with a column set optimized for the separation of low mass species. The analytical conditions used in the study are described in Table 1.

[0114] [Table 1]

[0115] The calibration used for Moore's calculation is a PS calibration, covering a range from 2,520,000 to 162 g. mol' 1 .

[0116] The calibration used is a mixed low-weight and medium-weight PS calibration from PSS Standards. The mass range is from 162 to 66,000 g. mol' 1 . Calibration allows the determination of Mn values ​​(g. mol' 1 ), Mw (g. mol' 1 ), D (Mw / Mn) in PS equivalent:

[0117] The calculation of the macrostructure does not take into account residual monomers because they are not considered part of the polymer.

[0118] The determination of the level of dimethyl sebacate, sebacic acid and glycerol is carried out by external calibration.

[0119] A standard range using samples of dimethyl sebacate, sebacic acid and glycerol at different concentrations was carried out.

[0120] The following polymer unit ratios are taken into account for the determination of the (1,2,3-triacylglyceride) unit ratio (in mol%, NMR determination) 13 C):

[0121] • a: 1-acylglyceride motif,

[0122] • b: 2-acylglyceride unit,

[0123] • c: 1,3-diacylglyceride unit,

[0124] • d: 1,2-diacylglyceride motif, and

[0125] • [1,2,3]: 1,2,3-triacylglyceride motif.

[0126] The ratio of (1,2,3-triacylglyceride) units to all acylglyceride units in the polymer therefore corresponds to the value 100 from which a, b, c and d are subtracted.

[0127] 1.3 Determination of the acid number of PGS polymers

[0128] The acid number is determined by acid-base titration. Weigh 0.1 g of sample (polymer) into a beaker. Add the solvent mixture (25 mL of propan-2-ol and 25 mL of diethyl ether (previously neutralized). Add 2-3 drops of phenolphthalein.

[0129] Titrate with 0.1 N KOH (the titer of which has been measured) until a pink color appears. The acid number is determined according to the formula:

[0130] With :

[0131] N = normality of 0.1 N potassium hydroxide solution,

[0132] V = volume, in mL, of the potassium hydroxide solution, m = mass, in g, of the test sample.

[0133] The limit of quantification of the method was set at 0.4 mg KOH / g. The limit of detection of the method was set at 0.1 mg KOH / g.

[0134] 1.4 Determination of the water content of PGS polymers

[0135] The water content is determined by dosage with a Karl Fischer titrator according to the ISO14897:2023 method.

[0136] The limit of quantification of the method was set at 0.01% by weight relative to the total weight of the polymer.

[0137] 1.5 Elemental determination of PGS polymers

[0138] The metal content is determined by ICP-AES atomic emission spectrometry. Approximately 100 mg of sample is weighed, the exact amount of sample is measured and introduced into a microwave reactor. Then, 5 mL of concentrated nitric acid is added. The sample is mineralized according to the “all matrices” program. The medium is quantitatively transferred into a 50 mL volumetric flask with ultrapure water. Ultrapure water is added to fill to the mark. The solution is filtered through a GHP filter with a porosity of 0.45 pm, then the residue is analyzed by ICP-AES (Arcos device from Spectro & PQ 9000 Analytik Jena). The elements N, K, Sn, Mg, Ca, Sr, Ba and Fe are retained and quantified.

[0139] 2. Examples of embodiments of the invention

[0140] 2.1. Synthesis of poly(glycerol sebacate)

[0141] The reactions are carried out in a 100 mL glass reactor stirred by a magnetic bar, topped with a glass distillation column and a condenser connected to a distillate recovery vessel. The reactor is connected to a ramp allowing nitrogen flushing or vacuuming of the reactor. A quantity of glycerol, a quantity of dicarboxylic acid diester - here dimethyl sebacate, are introduced at room temperature and under nitrogen flow (0.1 L / min) in step (a). The products are used as is, without further purification, apart from inerting under nitrogen for 15 min before introduction into the reactor. The molar ratios between the monomers are specified in Table 2a.

[0142] The nitrogen flow is maintained throughout step (b), under atmospheric pressure, with a stirring speed increased to 400 rpm and a heating setpoint fixed at a target temperature and for a defined time specified in table 2a.

[0143] Where appropriate, the catalyst is introduced into the reaction medium in a concentration defined at 0.5% w / w in Table 2a and ranging from 0.25% w / w to 0.5% w / w, as indicated in Table 3a, at this stage of the process and expressed relative to the total mass of monomers used.

[0144] The methanol distilled during this step is collected in the distillate recovery pot.

[0145] Next, a gradual vacuum is applied to the reactor contents in step (c). The pressure is slowly reduced over approximately 15 minutes to a target value of less than 10 mbar. Once the pressure in the reaction vessel has stabilized, the medium is left to react at a target temperature and for a number of hours defined in Table 2a during step (d).

[0146] The PGS produced is transferred from the reactor vessel to a container after returning the installation to atmospheric pressure and allowed to cool to room temperature. For the tests carried out according to the invention, a sample of the product is then diluted to 20% by mass in acetone, centrifuged for 10 min at 2500 rpm, then filtered on a Büchner funnel with a filter with a porosity of approximately 10 μm. The filtrate is left to evaporate at room temperature, before final drying in an oven overnight under reduced pressure, at 45 °C, under a nitrogen flow. The product is finally transferred to a freezer for storage, where it is frozen for at least approximately 24 hours before analysis.

[0147] 2.2. Results

[0148] Table 2a below gives the operating conditions of the synthesis process, Table 2b gives the results of the measurements carried out on the PGS obtained at the end of these syntheses.

[0149] PGS syntheses carried out without catalyst by acid and ester routes (not in accordance with the invention)

[0150] [Table 2a]

[0151] d1 = Esterification or transesterification duration, T1 = Esterification or transesterification temperature, d2 = Polycondensation duration, T2 = Polycondensation temperature

[0152] [Table 2b] LOQ: Limit of quantification, set at 0.4 mg KOH / g for the acid number and 0.01% for the water content; * carried out in the presence of 15%w / w water. ND: not determined due to insufficient conversion of monomers, ASL = free sebacic acid content, SDL = free dimethyl sebacate content, GL = free glycerol content, [1,2,3] = 1,2,3-triacylglyceride unit content.

[0153] According to the processes of Examples 2 and 3, carried out from sebacic acid, without catalyst over total durations of 4h and 6h respectively and without solvent - in accordance with the prior art, a PGS is obtained whose Mn reaches a value lower than 1000 g / mol with a residual monomer content higher than 5% by weight of the weight of the polymer obtained. According to the process described in Example 1, 24h of synthesis without catalyst, in the presence of water, is required to reach an Mn higher than 1000 g / mol with a residual monomer content lower than 5% by weight of the weight of the polymer obtained. Finally, according to example 4 produced from dimethyl sebacate, without catalyst over a total period of 6 hours and without solvent, a PGS is obtained which has a free sebacic acid level of 0%, an acid number < 0.5 mg KOH / g and a non-significant water level, but the PGS has a residual monomer level much higher than 5% and an Mn which reaches a value lower than 1000 g / mol.Example 5 is carried out with dimethyl sebacate and with a tin-based catalyst which is not part of the catalysts according to the invention, zinc octoate (SnOct?) which is toxic (reprotoxic according to the ECHA). Compared to Example 5, the conversion of the monomers is low and very few PGS oligomers were detected. The same observation can be made with the zinc acetate catalyst in Example 6, which is also not part of the catalysts of the invention. Finally, when the MgO and La?O3 catalysts are used alone in Examples 7 and 8, the conversion of the monomers is low and the synthesis only gives polymers of very low molecular weight with a very low yield.

[0154] Syntheses of PGS carried out in the presence of the catalyst (in accordance with the invention)

[0155] Table 3a below gives the operating conditions of the synthesis process according to the invention, from glycerol and dimethyl sebacate. Table 3b gives the results of the measurements carried out on the PGS obtained at the end of these syntheses.

[0156] The catalysts used are Strontium oxide (SrO), Calcium oxide (CaO) and Barium oxide (BaO) with a catalyst concentration given in % by mass relative to the total mass of monomers.

[0157] [Table 3a]

[0158] d1 = Transesterification time, T1 = Transesterification temperature, d2 = Polycondensation time, T2 = Polycondensation temperature

[0159] [Table 3b]

[0160] LOQ: Limit of quantification, set at 0.4 mg KOH / g for the acid number and 0.01% for the water content, SDL = Free dimethyl sebacate content, GL = Free glycerol content, [1,2,3] = 1,2,3-triacylglyceride unit content.

[0161] Elemental dosage of PGS prepared according to the invention

[0162] [Table 3c]

[0163] Comparison of examples 1 (non-compliant) with examples 9, 10 and 11 carried out at 160°C and 0.5% w / w of catalyst (compliant with the invention):

[0164] According to the processes carried out with the catalysts SrO, CaO and BaO, in accordance with the invention, PGS are obtained whose Mn reaches a value greater than 3000 g / mol, with a residual monomer content less than or equal to 3% by weight of the weight of the polymer obtained with a total duration of approximately 5 h, with a negligible acid number and water content. The acceleration of the reaction kinetics in view of that of example 1 is therefore very significant, as is the obtaining of a polymer without acid functions and a content of 1,2,3-triacylglyceride units which remains controlled.

[0165] Comparison of examples 1 (non-compliant) with examples 12 to 16 carried out at 150°C and 0.25% w / w to 0.5% w / w of catalyst (compliant with the invention):

[0166] According to the processes carried out with the catalysts SrO, CaO and BaO, in accordance with the invention, PGS are obtained whose Mn reaches a value greater than 2500 g / mol, with a residual monomer content less than or equal to 3.4% by weight of the weight of the polymer obtained with a total duration of less than approximately 6 h, with a negligible acid number and water content. The acceleration of the reaction kinetics in view of that of example 1 is therefore very significant, as is the obtaining of a polymer without acid functions and a content of 1,2,3-triacylglyceride units which remains controlled.

[0167] Comparison of examples 1 (non-compliant) with examples 17 to 19 carried out at 160°C and 0.25% w / w of catalysts (compliant with the invention):

[0168] According to the process carried out with the catalysts SrO, CaO and BaO in accordance with the invention, a PGS is obtained whose Mn reaches a value greater than 3000 g / mol, with a residual monomer content less than or equal to 2.9% by weight of the weight of the polymer obtained with a total duration of approximately 5 h, with a negligible acid number and water content. The acceleration of the reaction kinetics in view of that of example 1 is therefore very significant, as is the obtaining of a polymer without acid functions and a content of 1,2,3-triacylglyceride units which remains controlled.

[0169] Comparison of examples 1 (non-compliant) with examples 20 to 23 carried out at 170°C and 0.25% w / w and 0.5% w / w of catalyst (compliant with the invention):

[0170] According to the processes carried out with the catalysts SrO, CaO and BaO, in accordance with the invention, PGS are obtained whose Mn reaches a value greater than 3100 g / mol, with a residual monomer content less than or equal to 2.9% by weight of the weight of the polymer obtained with a total duration of approximately 5 h, with a negligible acid number and water content. The acceleration of the reaction kinetics in view of that of example 1 is therefore very significant, as is the obtaining of a polymer without acid functions and a content of 1,2,3-triacylglyceride units which remains controlled.

[0171] Comparison of examples 2 and 3 (non-compliant) with examples 9 to 23 (compliant with the invention):

[0172] It is observed that with the process carried out by acid route and with reaction times of the same order of magnitude, the molar masses are very significantly lower with high residual monomer levels, acid numbers and high free water levels.

[0173] Comparison of examples 4 to 8 (non-compliant) with examples 9 to 23 (compliant with the invention):

[0174] It is observed in the same way as previously that despite the use of dimethyl sebacate in Examples 4 to 8, without catalyst or with catalysts which are not part of the scope of the invention, in syntheses with reaction times of the same order of magnitude, the molar masses are very significantly lower with high residual monomer levels. Finally, it is observed that the residual quantities of metallic elements in the examples according to the invention are less than 5000 ppm, or 0.5% by mass for the elements Sr, Ca and Ba, as visible in Table 3c, using a conventional filter with a porosity of 10 pm. No element of the transition metal family was detected.

Claims

CLAIMS 1. Process for the synthesis of a polyester from a polyol and a dicarboxylic acid diester comprising the following steps: (a) contacting polyol monomers, preferably glycerol, and dicarboxylic acid diester, with a polyol:dicarboxylic acid diester molar ratio ranging from 0.5:1 to 10:1; (b) transesterification under an inert atmosphere at a temperature above 25°C; (c) placing the reaction medium obtained following step (b) under vacuum, preferably at a pressure less than or equal to 100 mbara (10000 Pa); (d) vacuum polycondensation, preferably at a pressure identical to or lower than that of step (c), at a temperature above 25°C; said process comprising the introduction of a heterogeneous basic catalyst selected from the group consisting of CaO, SrO, BaO, and mixtures thereof.

2. Method according to claim 1, characterized in that the molar ratio of polyokdiester to dicarboxylic acid varies from 0.9:1 to 2:1, preferably from 1:1 to 1.5:

1.

3. Process according to claim 1 or 2, characterized in that the dicarboxylic acid diester is a compound of the following formula (I): ROOC-(CH2) n-COOR' (I) in which R and R' independently represent a linear or branched alkyl chain, or a vinyl function, and n represents an integer ranging from 1 to 30, preferably ranging from 1 to 10, preferably the dicarboxylic acid diester is chosen from the group consisting of malonic acid diesters, succinic acid diesters, glutaric acid diesters, adipic acid diesters, pimelic acid diesters, suberic acid diesters, azelaic acid diesters, sebacic acid diesters and mixtures thereof, more preferably dimethyl malonate, dimethyl succinate, dimethyl glutarate, dimethyl adipate, dimethyl pimelate, dimethyl suberate, dimethyl azelate, dimethyl sebacate dimethyl, and mixtures thereof, even more preferably the dicarboxylic acid diester is dimethyl sebacate. TJ 4. Method according to any one of claims 1 to 3, characterized in that step (b) is carried out at a temperature below 200°C, preferably at a temperature varying from 65°C to 200°C, preferably from 120°C to 180°C.

5. Method according to any one of claims 1 to 4, characterized in that step (b) is carried out for a duration varying from 0.25 h to 10 h, preferably from 1 h to 5 h.

6. Method according to any one of claims 1 to 5, characterized in that step (d) is carried out at a temperature below 250°C, preferably at a temperature ranging from 65°C to 250°C, preferably from 80°C to 200°C, more preferably from 100°C to 180°C.

7. Method according to any one of claims 1 to 6, characterized in that step (d) is carried out for a duration varying from 0.1 h to 12 h, preferably from 0.5 h to 4 h.

8. Process according to any one of claims 1 to 7, characterized in that the introduction of the heterogeneous basic catalyst is carried out at a stage chosen from: during stage (b), at the end of the transesterification of stage (b), before the evacuation of stage (c) or after the evacuation of stage (c), preferably during stage (b) during the rise in temperature towards the reaction temperature.

9. Process according to any one of claims 1 to 8, characterized in that the catalyst is introduced in an amount ranging from 0.01% to 5% by weight, relative to the total weight of polyol monomers and dicarboxylic acid diester, preferably from 0.02% to 3% by weight, more preferably from 0.05% to 1% by weight.

10. Process according to any one of claims 1 to 9, characterized in that the polycondensation step (d) further comprises removal of the alcohol produced by the polycondensation reaction, preferably by distillation.

11. Method according to any one of claims 1 to 10, characterized in that the method further comprises a step (e) carried out after step (d), said step (e) being a step of recovering the catalyst, preferably by filtration.

12. Polyester obtainable by the process according to any one of claims 1 to 11.

13. Polyester of polyol and dicarboxylic acid diester, preferably poly(glycerol sebacate), having a number average molar mass Mn greater than or equal to 2500 g / mol, preferably 3000 g / mol, and an acid number less than 2 mg KOH / g of polymer.

14. Polyester according to claim 13 further having one or more of the following characteristics, preferably all of the following characteristics: a residual monomer content of less than 5% by weight relative to the total weight of the polymer, a water content of less than 0.3% by weight relative to the total weight of the polymer, a Ca, Sr or Ba metal residue content of less than 1%, preferably less than 0.5%, preferably less than 0.01% by weight of the polymer, a (1,2,3-triacylglyceride) unit content ranging from 10 to 20 mol% relative to all the acylglyceride units of the polymer, a dispersity D of less than 18, a transition metal content of less than 0.05% by weight relative to the total weight of the polymer, a Sc or Bi metal residue content of less than 0.5% by weight of the polymer.

15. Polyester according to claim 13 or 14, having the following characteristics: a level of Ca, Sr or Ba metal residues of less than 0.01% by weight of the polymer, a level of transition metals of less than 0.05% by weight relative to the total weight of the polymer, a level of Sc or Bi metal residues of less than 0.1% by weight of the polymer, and an acid number of less than 0.4 mg KOH / g of polymer.

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