Synthesis method of glycerol polyester

Abstract

The present invention relates to a process for preparing a polyester of glycerol and a dicarboxylic acid, the process comprising: (a) contacting monomers comprising at least glycerol and dicarboxylic acid in the presence of water in an inert atmosphere at a temperature of less than 100 DEG C wherein the molar ratio of glycerol / dicarboxylic acid ranges from 0.5 / 1 to 10 / 1; (b) carrying out esterification in an inert atmosphere at a temperature higher than 110 DEG C; (c) at a temperature higher than 110 DEG C, vacuumizing the reaction medium to a pressure lower than 100 mbar; (d) maintaining a vacuum and a temperature above 110 DEG C to carry out polycondensation, said process comprising: at the end of the esterification of step (b), before or after the evacuation of step (c), introducing a polycondensation catalyst in an amount of less than or equal to 5000 ppm with respect to the total weight of monomers, said catalyst being a tin-based food grade catalyst, the organic tin compounds are selected from organic tin compounds containing carboxyl functional groups (-C (O) OH), organic tin compounds containing functional groups (-Sn (O) OH) and mono-butyltin tris (2-ethylhexanoate). The present invention relates to a process for synthesizing glycerol polyesters having a residual monomer content of less than 5% by weight, based on the weight of the polymer, a high number average molar mass Mn of greater than 2500 g / mol, a dispersity of less than or equal to 10 and a 1, 2, 3-triacylglyceride unit content of less than 15 mol% with respect to all units of the polymer, in particular to the synthesis of glycerol polyesters having a residual monomer content of less than 5% by weight, based on the weight of the polymer, a high number average molar mass Mn of greater than 2500 g / mol.

Description

Technical Field

[0001] The present invention relates to the synthesis of polyesters, which are obtained by esterification of the hydroxyl groups of a polyol with the carboxyl groups of a diacid through a polycondensation reaction. Background Technology

[0002] A conventional method for synthesizing polymers of glycerol and dicarboxylic acids involves a prolonged reaction in a high-temperature molten state, including an esterification step followed by polycondensation under extremely low pressure. One such method is described, for example, in EP1448656A1. The constituent monomers of this polymer exhibit different affinities. Therefore, glycerol is typically poorly soluble with dicarboxylic acids. This poor affinity between monomers makes the reaction difficult to control and repeat, as the reaction medium is difficult to homogenize. This results in uncontrolled macroscopic and microscopic structural properties of the resulting polymer, leading to limited physicochemical properties that fail to meet application requirements.

[0003] Document EP3149067A1 describes a method for synthesizing polymers of glycerol and dicarboxylic acids. This method improves upon the process by employing a water-mediated synthesis method at the start of esterification. This facilitates the generation of homogeneous media and polymers with more controllable physicochemical properties, thus enabling certain applications, such as those requiring strict control of molar mass distribution, particularly the controlled release of substances.

[0004] Other methods for synthesizing glycerol polyesters have been described. For example, the use of metal catalysts to produce polyesters (specifically PGS) formed by the condensation of glycerol with dicarboxylic acids has been considered. Such metal catalysts have toxic properties and are not always compatible with the use of these polyesters in the preparation of biomaterials, which require synthesis in environments with highly controlled toxicity. Polymer 55 (2014) 5065-5072 describes the synthesis of a polymer of glycerol and dicarboxylic acid (adipic acid) in a bulk medium (solvent-free) in the presence of dibutyltin oxide, exhibiting some acute toxicity. The resulting polymer was hyperbranched and had a relatively low molar mass, even after 11.5 hours of reaction.

[0005] As shown in the literature, the glycerol monomers involved in the preparation of glycerol polyesters are trifunctional. In other words, during polymerization, the esterification reaction can occur on the three alcohol functional groups of glycerol. This results in the formation of 1,2,3-triacylglycerol ester units, leading to crosslinking or branching points in the polymer, thus forming a branched polyester structure. When these branching points are not controlled and addressed, a gel-like product may be rapidly formed, which is difficult to flow, poses a risk of equipment blockage and breakage, and is complex to mold.

[0006] There remains a need to develop efficient methods for synthesizing biocompatible polymers (more specifically, PGS) of glycerol and dicarboxylic acids, with shortened reaction times to improve industrial compatibility. In this context, the necessity of controlling the structure of the resulting polymer must be kept in mind, particularly by ensuring a high molecular weight greater than 2500 g / mol while maintaining acceptable dispersibility and controllable branching.

[0007] Furthermore, shortening the reaction time to improve method efficiency may result in the formation of a certain amount of residual monomers, which can complicate the control of the thermomechanical properties of the resulting polymer. This is why it is essential to develop efficient methods for synthesizing biocompatible polymers (more specifically, PGS) of glycerol and dicarboxylic acids by controlling the amount of residual monomers.

[0008] Furthermore, some applications of this type of polyester require synthesis in an environment with highly controlled toxicity, which must also be taken into consideration. Summary of the Invention

[0009] Technical issues

[0010] The object of this invention is to provide an efficient method for synthesizing a polymer (more specifically, PGS) of glycerol and dicarboxylic acid, which satisfies all the constraints defined above and solves the problems encountered in existing methods. Specifically, the object of this invention is to provide an efficient method for synthesizing a polymer (more specifically, PGS) of glycerol and dicarboxylic acid, which has a shortened reaction time, is suitable for industrial applications, and controls the structure of the resulting polymer, particularly by ensuring a high molar mass greater than 2500 g / mol, by maintaining acceptable dispersibility and controlled 1,2,3-triacylglycerol ester unit content, while minimizing the amount of residual monomer.

[0011] Disclosure of the present invention

[0012] Through continuous efforts, the applicant has developed a method for synthesizing polymers of glycerol and dicarboxylic acids. This method possesses accelerated kinetic properties, enabling the overcoming of the aforementioned synthetic difficulties and providing an acceptable toxicological environment. Specifically, the applicant has developed a synthetic method to obtain polymers of glycerol and dicarboxylic acids having a high number-average molar mass greater than 2500 g / mol, a controlled dispersion of less than or equal to 10, a 1,2,3-triacylglycerol ester unit content of less than 15 mol% relative to all units of the polymer with no gel formation, and a low residual monomer content of less than 5 wt% relative to the polymer.

[0013] Therefore, the first subject of this invention is a method for preparing a polymer of glycerol and dicarboxylic acid, the method comprising:

[0014] (a) At a temperature below 100°C, a monomer comprising at least glycerol and dicarboxylic acid is contacted in the presence of water, wherein the molar ratio of glycerol / dicarboxylic acid ranges from 0.5 / 1 to 10 / 1.

[0015] (b) Esterification was carried out in an inert atmosphere at a temperature above 100°C;

[0016] (c) At a temperature above 110°C, the reaction medium is evacuated to a pressure below 100 mbar (absolute pressure);

[0017] (d) Maintain a vacuum and a temperature above 110°C to carry out polycondensation;

[0018] The method includes introducing a polycondensation catalyst at the end of esterification in step (b), before or after vacuuming in step (c), in an amount less than or equal to 5000 ppm relative to the total weight of the monomers, said catalyst being a tin-based food-grade catalyst selected from organotin compounds containing a carboxyl functional group (-C(O)OH), organotin compounds containing a functional group (-Sn(O)OH), and bis(2-ethylhexanoic acid)tin.

[0019] More specifically, the catalyst is food-grade monobutyltin oxide, also known as butyl stannic acid, which is sold by PMCorganometallix under the name FASCAT 9100.

[0020] Another subject of this invention is a polymer of glycerol and dicarboxylic acid, which has:

[0021] - Through SEC / RI and 13 The residual glycerol and dicarboxylic acid monomer content, measured by C NMR, is less than 5% by weight based on the weight of the obtained polymer;

[0022] - High number-average molar mass Mn greater than 2500 g / mol;

[0023] -Dispersion less than or equal to 10;

[0024] - Less than 15 mol% of (1,2,3-triacylglycerol) units relative to all units of the polymer.

[0025] Summary of the Invention

[0026] The subject matter of this invention is at least one embodiment listed in the following points, which will be described in more detail below:

[0027] 1. A method for preparing a polyester of glycerol and dicarboxylic acid, the method comprising:

[0028] (a) At a temperature below 100°C, a monomer comprising at least glycerol and the corresponding dicarboxylic acid is contacted in the presence of water, wherein the molar ratio of glycerol / dicarboxylic acid ranges from 0.5 / 1 to 10 / 1.

[0029] (b) Esterification is carried out in an inert atmosphere at a temperature above 110°C (preferably in the range of 130°C to 180°C);

[0030] (c) At a temperature above 110°C (preferably in the range of 130°C to 180°C), the reaction medium is evacuated to a pressure below 100 mbar (absolute pressure);

[0031] (d) Maintain a vacuum and a temperature above 110°C (preferably in the range of 130°C to 180°C) to carry out polycondensation;

[0032] The method includes introducing a polycondensation catalyst at the end of esterification in step (b), before or after vacuuming in step (c), in an amount less than or equal to 5000 ppm relative to the total weight of the monomers, wherein the catalyst is a tin-based food-grade catalyst selected from organotin compounds containing a carboxyl functional group (-C(O)OH), organotin compounds containing a functional group (-Sn(O)OH), and tris(2-ethylhexanoic acid) monobutyltin.

[0033] 2. The method according to embodiment 1, wherein the dicarboxylic acid is aliphatic and contains 3 to 36 carbon atoms.

[0034] 3. The method according to any one of the foregoing embodiments, wherein the dicarboxylic acid has the formula [HOOC-(CH2)]. n -COOH], where n is a number from 1 to 30, preferably a number from 1 to 10.

[0035] 4. The method according to any one of the foregoing embodiments, wherein the dicarboxylic acid is selected from malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, octanoic acid, azelaic acid, sebacic acid, or a mixture of two or more of these dicarboxylic acids.

[0036] 5. The method according to any one of the foregoing embodiments, wherein the dicarboxylic acid includes sebacic acid.

[0037] 6. The method according to any one of the foregoing embodiments, wherein the dicarboxylic acid is sebacic acid.

[0038] 7. The method according to any one of the foregoing embodiments, wherein the molar ratio of glycerol / diaclic acid ranges from 0.9 / 1 to 2 / 1, preferably from 1 / 1 to 1.5 / 1.

[0039] 8. The method according to any one of the foregoing embodiments, wherein the contact of the monomers is achieved by introducing the dicarboxylic acid monomer into a mixture comprising glycerol monomer and water.

[0040] 9. The method according to any one of the foregoing embodiments, wherein the diacid monomer is introduced in liquid form into a mixture comprising glycerol monomer and water.

[0041] 10. The method according to any one of the foregoing embodiments, wherein the diacid monomer is introduced in solid form into a mixture comprising glycerol monomer and water.

[0042] 11. The method according to any one of the foregoing embodiments, wherein the diacid monomer is introduced in solid form into a mixture comprising glycerol monomer and water, and after the monomer contact in step (a), the step of melting the diacid monomer in an aqueous medium is performed.

[0043] 12. The method according to any one of the foregoing embodiments, wherein, at the end of monomer contact in step (a), the reaction medium is refluxed.

[0044] 13. The method according to any one of the foregoing embodiments, wherein the method includes, at the end of step (a), removing the water introduced to contact the monomer, preferably by distillation.

[0045] 14. The method according to any one of the foregoing embodiments, wherein the method includes a water removal step, preferably by distillation, which is performed after or simultaneously with the esterification step (b), the polycondensation step (c), or the esterification step (b) and the polycondensation step (c).

[0046] 15. The method according to any one of the foregoing embodiments, wherein the reaction medium in step (c) is evacuated at a pressure of less than 50 mbar (absolute pressure), preferably less than 10 mbar (absolute pressure).

[0047] 16. The method according to any one of the foregoing embodiments, wherein the tin-based food-grade catalyst is selected from food-grade alkyltin compounds, the alkyltin compounds comprising a carboxyl functional group (-C(O)OH) or a functional group (-Sn(O)OH), the alkyl group having 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms.

[0048] 17. The method according to any one of embodiments 1 to 15, wherein the tin-based food-grade catalyst is selected from food-grade monobutyltin oxide (or stannic acid) and food-grade tris(2-ethylhexanoic acid) monobutyltin.

[0049] 18. The method according to any one of the foregoing embodiments, wherein the tin-based food-grade catalyst is food-grade monobutyltin oxide (or stannic acid).

[0050] 19. The method according to any one of the foregoing embodiments, wherein the amount of catalyst introduced is less than or equal to 3000 ppm.

[0051] 20. The method according to any one of the foregoing embodiments, wherein the amount of catalyst introduced is greater than or equal to 1000 ppm.

[0052] 21. A polyester of glycerol and dicarboxylic acid, which can be obtained by the method defined in any of the foregoing embodiments.

[0053] 22. A polyester of glycerol and dicarboxylic acid, comprising:

[0054] - Residual monomer content of less than 5% by weight based on polymer weight;

[0055] -Number-average molar mass Mn greater than 2500 g / mol;

[0056] -Dispersion less than or equal to 10 (Mw / Mn);

[0057] - Less than 15 mol% of (1,2,3-triacylglycerol) units relative to all units of the polymer.

[0058] 23. The polyester of glycerol and dicarboxylic acid according to embodiment 21, wherein the number-average molar mass Mn is less than or equal to 2700 g / mol.

[0059] 24. The polyester of glycerol and dicarboxylic acid according to any one of embodiments 21 and 23, wherein the number-average molar mass Mn is less than 3500 g / mol, preferably less than 3000 g / mol.

[0060] 25. The polyester of glycerol and dicarboxylic acid according to any one of embodiments 21 to 24, wherein the dispersion degree is... (Mw / Mn) is less than or equal to 5.

[0061] definition

[0062] In this document, unless otherwise stated, all percentages (%) shown are molar percentages (%).

[0063] In this article, unless otherwise stated, pressure is expressed in absolute pressure, in units of "bara".

[0064] Furthermore, any numerical interval expressed as "between a and b" represents a range of values ​​from greater than a to less than b (i.e., excluding the extreme values ​​a and b), while any numerical interval expressed as "from a to b" means a range of values ​​from a to b (i.e., including the strict extreme values ​​a and b). In this document, when a numerical interval is expressed as "from a to b," it is also preferable to represent the interval represented by the expression "between a and b."

[0065] When referring to a "major" compound, for the purposes of this invention, this means that among compounds of the same type in the composition, the compound that is dominant, that is, the compound that constitutes the largest amount by mass among compounds of the same type. Conversely, a "minor" compound refers to a compound that does not constitute the largest mass fraction among compounds of the same type. Preferably, "major" is understood to mean a mass percentage exceeding 50%; it is also referred to as "major" when the compound accounts for 100% by mass.

[0066] When referring to a "food-grade" catalyst, in the context of this invention, it should be understood as a catalyst that is safe for human consumption. It conforms to FDA (U.S. Food and Drug Administration) standards 21 CFR 175.300, 21 CFR 177.2420, and 21 CFR 175.105.

[0067] The compounds mentioned in this specification may be fossil-derived or bio-based. In the latter case, they may be obtained in whole or in part from biomass or from renewable raw materials derived from biomass. Similarly, the compounds mentioned may also be derived from the recycling of used materials, i.e., they may be obtained in whole or in part from the recycling process or from raw materials that are themselves generated by the recycling process. This particularly relates to monomers. Detailed Implementation

[0068] The method for preparing a polyester of glycerol and dicarboxylic acid according to the present invention includes steps (a), (b), (c) and (d) as presented in Embodiment 1 above.

[0069] According to step (a) of the method of the present invention, glycerol and dicarboxylic acid monomer are contacted in water.

[0070] The dicarboxylic acid monomer according to the invention can be aliphatic, aromatic, or aliphatic / aromatic. In the latter case, the diacid comprises both an aliphatic and an aromatic moiety. It preferably contains 4 to 36 carbon atoms. "Aliphatic" refers to a straight-chain, cyclic, or branched aliphatic chain, whether saturated or unsaturated.

[0071] According to a preferred variant of the invention, the dicarboxylic acid monomer is an aliphatic monomer containing 3 to 36 carbon atoms.

[0072] Based on these variants, the dicarboxylic acid monomer can preferably correspond to the formula [HOOC-(CH2)]. n -COOH], where n is a number from 1 to 30, preferably a number from 1 to 10.

[0073] Preferably, according to these variants of the invention, the dicarboxylic acid monomer may be selected from malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, octanoic acid, azelaic acid, sebacic acid, or a mixture of two or more of these dicarboxylic acids.

[0074] According to a variant of the invention, the dicarboxylic acid monomer can be a mixture of at least two dicarboxylic acids. Preferably, in this case, the dicarboxylic acid monomer includes sebacic acid.

[0075] According to a preferred variant of the invention, the dicarboxylic acid monomer is sebacic acid.

[0076] According to a preferred variant of the invention, the dicarboxylic acid monomer and glycerol are the only monomers. In this case, very preferably, the sebacic acid monomer and glycerol are the only monomers.

[0077] According to any variant of the invention, the monomers are contacted in a vessel or reactor. Subsequent reactions can be carried out in the same reactor. Those skilled in the art can adjust the type of vessel or reactor to suit process requirements, taking into account heating and pressure conditions.

[0078] According to a variant of the invention, the contact of the monomers in step (a) is carried out by adding water to the mixture of glycerol and dicarboxylic acid. Adding water to the monomer mixture homogenizes the mixture, thereby reducing its overall viscosity. To facilitate this homogenization, stirring is installed in a known manner.

[0079] According to these variants, the amount of water added to the monomer is between 0% and 100% of the mass of the monomer used, preferably in the range of 5% to 50% of the mass of the monomer used, and more preferably in the range of 10% to 40% of the mass of the monomer used.

[0080] According to other particularly preferred variants of the invention, the homogenization of the reaction mixture after the addition of the dicarboxylic acid is improved by contacting the monomer with the dicarboxylic acid monomer by introducing it into a mixture comprising glycerol and water. To facilitate this homogenization, a stirring device is installed in a known manner.

[0081] According to these preferred variants, prior to step (a), glycerol is mixed with water, with the molar ratio of glycerol to water advantageously ranging from 1 / 10 to 10 / 1.

[0082] The step of mixing glycerol and the aqueous solution can be carried out in a container at ambient temperature (20°C to 30°C, typically about 23°C at atmospheric pressure), which can be the same as step (a). This premixing may optionally include heating the glycerol and water to a temperature of about 50°C to 100°C. The medium is then heated for a time sufficient to allow the glycerol to dissolve or disperse uniformly in the water. To promote homogenization of the medium, stirring is installed in a known manner, regardless of whether heating is used.

[0083] According to any of these variants, the dicarboxylic acid monomer can be introduced into a mixture containing glycerol and water in liquid or solid form, preferably in solid form.

[0084] According to the invention, the monomers are contacted at a temperature below 100°C. Advantageously, especially when the dicarboxylic acid monomer is introduced in solid form, the contacting of the monomers is followed by a step of melting the dicarboxylic acid monomer in an aqueous medium.

[0085] According to an advantageous embodiment of the invention, after the monomers are contacted in step (a), the reaction medium is heated and optionally refluxed. Heating the medium allows the dicarboxylic acid monomers to melt, for example, when introduced in solid form. For example, sebacic acid is slightly soluble in water at ambient temperature, and this solubility increases with increasing temperature. The reaction medium is heated to a temperature of approximately 50°C to 150°C and maintained for a time sufficient to allow the monomers to melt and mix thoroughly. During this heating step, care must be taken to prevent the condensation of vapors in the reactor in order to obtain a homogeneous medium; for example, the column is configured for total reflux according to methods known to those skilled in the art.

[0086] Depending on other variants, such as when dicarboxylic acids are introduced in liquid form at room temperature, a reflux step is optional.

[0087] Those skilled in the art will understand that in some embodiments, in order to shorten reflux time and / or in cases where the diacid monomer melts only at high temperatures, the reaction medium can be pressurized to achieve temperatures up to 200°C or higher.

[0088] In step (a) of the method according to the invention, glycerol and dicarboxylic acid monomers are contacted in an aqueous medium, wherein the molar ratio of glycerol / dicarboxylic acid is between 0.5 / 1 and 10 / 1, preferably between 0.9 / 1 and 2 / 1, and more preferably between 1 / 1 and 1.5 / 1.

[0089] At the end of step (a), the water added for this step can be removed, for example by distillation or any other known method of water removal. The monomers are then uniformly mixed in liquid form, allowing subsequent esterification and polycondensation reactions to proceed in a controlled manner.

[0090] The water removal process may include heating the reaction medium to about 50°C to 200°C at atmospheric pressure, more specifically, to about 80°C to 180°C, although it is also conceivable to remove water at lower pressures and lower temperatures.

[0091] When water is removed by distillation, this can be done simultaneously with stirring and / or by purging the contents of the container under an inert gas atmosphere.

[0092] At the end of the process of removing the added water, according to step (b) of the method of the invention, glycerol and dicarboxylic acid monomer are reacted with each other under an inert atmosphere at a temperature above 110°C (preferably from 110°C to 200°C, more preferably from 120°C to 180°C, even more preferably from 130°C to 180°C) for a period of 4 to 48 hours.

[0093] A reaction under an inert atmosphere should be understood as a reaction in an inert gas (e.g., nitrogen, carbon dioxide, rare gases or mixtures thereof) in a known manner.

[0094] The esterification step (b) is preferably carried out at atmospheric pressure. Those skilled in the art will understand that an alternative is to carry out the step at a lower pressure to reduce the temperature and / or pressure, for example, between 1 bar (absolute pressure) and 100 millibar (absolute pressure).

[0095] According to an advantageous variant of the invention, in step (b), water generated as a byproduct of the esterification reaction is removed, for example by distillation or any other known method of water removal. According to these variants, water removal (e.g., by distillation) can be carried out directly after the step of removing the initially added water. Therefore, at this stage of the method, part of the water removed is the water added for carrying out step (a), while another part is a byproduct of the monomers reacting with each other. By measuring the amount of water removed, it is possible to determine when the water in step (a) has been completely removed. Thus, the starting point of step (b) can be determined.

[0096] The method of the present invention continues to step (c), in which the reaction medium is evacuated. The term "evacuation" is understood herein to mean reducing the pressure until it reaches a value less than or equal to 100 mbar (absolute pressure), preferably less than 50 mbar (absolute pressure), and more preferably less than 10 mbar (absolute pressure). According to one embodiment, the pressure is in the range of 5 mbar (absolute pressure) to 10 mbar (absolute pressure).

[0097] The key element of this invention is that a catalyst is introduced into the reaction medium at the end of step (b) in an amount less than or equal to 5000 ppm relative to the total weight of the monomers, preferably greater than or equal to 2500 ppm. The catalyst is a tin-based food-grade catalyst selected from organotin compounds containing carboxyl functional groups (-C(O)OH) or functional groups (-Sn(O)OH).

[0098] "Food-grade catalyst" should be understood as a catalyst suitable for food contact (for animals and humans) that meets the requirements to ensure that the catalyst does not pose a toxic risk to the polyester produced.

[0099] The introduction of the catalyst at the end of step (b) can be performed before or after the evacuation in step (c), but for ease of operation, it is preferred to perform it before the evacuation in step (c).

[0100] According to a variant of the invention, at the end of step (b) and before the evacuation in step (c), the pressure can be reduced in stages to an intermediate pressure between atmospheric pressure and vacuum. Any method known to those skilled in the art can be used to reduce the pressure, particularly using peristaltic pumps, diaphragm pumps, rotary pumps, etc. This intermediate pressure is less than 1 bar, for example, varying from 800 mbar (absolute pressure) to 50 mbar (absolute pressure).

[0101] According to these variations, the catalyst can be introduced directly at the end of step (b) before the pressure drops to an intermediate pressure, or during the pressure reduction process (e.g., when a steady state is reached), or just before the vacuum is drawn in step (c), or after the vacuum is drawn in step (c).

[0102] Catalysts can be introduced directly in solid form, dissolved form, or suspended in a liquid (e.g., water). Catalysts can be mixed with the reaction medium in a known manner, such as under stirring.

[0103] The amount of catalyst introduced according to the invention is less than or equal to 5000 ppm relative to the mass of the introduced monomer, preferably less than or equal to 3000 ppm.

[0104] Typically, the amount of catalyst introduced is at least 200 ppm relative to the mass of the introduced monomer. This minimum catalyst value achieves optimal catalytic activity. Therefore, the amount of catalyst introduced according to the invention is preferably in the range of 200 ppm to 5000 ppm, more preferably in the range of 200 ppm to 3000 ppm. According to variations of the invention, the amount of catalyst introduced according to the invention is preferably greater than or equal to 1000 ppm relative to the mass of the introduced monomer. Therefore, according to these variations, the amount of catalyst introduced according to the invention is in the range of 1000 ppm to 5000 ppm, more preferably in the range of 1000 ppm to 3000 ppm.

[0105] The catalyst according to the present invention is a tin-based food-grade catalyst, which is selected from organotin compounds containing a carboxyl functional group (-C(O)OH), organotin compounds containing a functional group (-Sn(O)OH), and tris(2-ethylhexanoic acid) monobutyltin.

[0106] According to a specific variant of the invention, the catalyst is selected from alkyltin compounds containing a carboxyl functional group (-C(O)OH) or a functional group (-Sn(O)OH) (wherein the alkyl group has 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms), and tris(2-ethylhexanoic acid) monobutyltin. Among these specific compounds, food-grade monobutyltin oxide (or stannic acid) and food-grade tris(2-ethylhexanoic acid) monobutyltin may be mentioned.

[0107] According to a preferred variant of the invention, the catalyst is food-grade monobutyltin oxide (or stannic acid).

[0108] Examples of catalysts that can be used for the purposes of this invention include monobutyltin oxide sold by PMC Organometallix under the name FASCAT 9100 and tris(2-ethylhexanoic acid) monobutyltin sold under the name FASCAT 9102. Particularly preferred is the monobutyltin oxide catalyst sold by PMC Organometallix under the name FASCAT 9100.

[0109] At the end of step (c) and the introduction of the catalyst into the reaction medium, the method of the present invention continues with the polycondensation step (d) at a temperature above 110°C, preferably in the range of 110°C to 250°C, more preferably 120°C to 200°C, and even more preferably 130°C to 180°C, for a period of 0 to 10 hours under vacuum.

[0110] Polycondensation can then be carried out immediately (i.e., within the time required to reach a vacuum) or over a period of up to 10 hours.

[0111] According to an advantageous variant of the invention, in step (d), water produced by the polycondensation reaction is removed, for example by distillation or any other known method of water removal. According to an advantageous variant of the invention, in steps (b) and (d), water produced by the esterification and polycondensation reactions is removed, for example by distillation or any other known method of water removal. According to these variants, water removal (e.g., by distillation) can be carried out sequentially with the step of removing the initially added water. When water is removed by distillation, this can be carried out simultaneously with stirring and / or by purging the contents of the container under an inert gas atmosphere.

[0112] At the end of these steps according to the method of the invention, the resulting polyester can be recovered in a known manner, stored if necessary, and optionally processed for later use.

[0113] Polyesters of glycerol and dicarboxylic acid obtained according to the method of the present invention described above, according to any variant thereof, are also the subject of the present invention.

[0114] All variations and aspects (whether preferred or not) of the method of the present invention provide a polyester of glycerol and dicarboxylic acid, more specifically poly(glycerol sebacate) or PGS, which advantageously possesses the following physicochemical properties:

[0115] - The residual monomer content is less than 5% by weight, preferably less than 2% by weight, based on the polymer weight.

[0116] - High number-average molar mass Mn greater than 2500 g / mol, preferably greater than or equal to 2700 g / mol.

[0117] - A dispersion of less than or equal to 10, preferably less than or equal to 5.

[0118] - Less than 15 mol% of 1,2,3-triacylglycerol units relative to all units of the polymer.

[0119] Such polyesters also constitute the subject of this invention.

[0120] Advantageously, according to a preferred variant of the invention, the weight-average molar mass of such polyester is less than or equal to 3500 g / mol, preferably less than or equal to 3000 g / mol.

[0121] The physicochemical properties of the polyesters obtained using the method of this invention demonstrate favorable homogeneity and repeatability (due to a controlled dispersion of 10 or lower), and particularly improved processing properties (due to the improved processing performance). 13The low branching degree (less than 15 mol% of 1,2,3-triacylglycerol units relative to the total acylglycerol functional groups present in the polymer, as determined by C NMR) is actually expressed as the molar ratio of the 1,2,3-triacylglycerol unit content to the sum of the contents of all acylglycerol functional groups in the polymer.

[0122] The residual monomer content was determined according to the method described in the examples.

[0123] According to the method described in the examples, the macroscopic structure (Mn, Mw, and...) of the polyester of glycerol and dicarboxylic acid was determined by SEC. (Mw / Mn)).

[0124] According to the method described in the embodiments, by 13 The microstructure of the polyester of glycerol and dicarboxylic acid was determined by C NMR.

[0125] The above and other features of the invention will become clearer by reading the following description of several exemplary embodiments of the invention, given in a non-limiting manner.

[0126] Exemplary embodiments of the present invention

[0127] Synthesis of 1-poly(glycerol sebacate):

[0128] Table 1 shows the molar ratios between monomers and the reaction conditions for each step in the synthesis of PGS.

[0129] The general procedure for all tests is as follows:

[0130] In a 500 mL jacketed reactor (equipped with a total reflux distillation column at the top and a condenser connected to a distillate recovery vessel), a measured amount of glycerol and a measured amount of water were mixed at ambient temperature under a nitrogen flow (0.1 L / min). The mixture was gently stirred (50 rpm) for 5 minutes. After the glycerol dissolved, a measured amount of sebacic acid was added to the aqueous mixture in the reactor. Finally, the remaining water was added to the medium to achieve the target monomer concentration. The reactor vessel was then heated to the jacket temperature described in Table 1. As the acid melted and its solubility increased, the stirring speed was gradually increased to 100 rpm, then to 150 rpm. When the medium in the vessel became clear (approximately 95°C), the stirring speed was finally set to 200 rpm, and the medium was placed in reflux. When the vapor temperature at the top of the distillation column reached 98°C, and after a 15-minute equilibration period, the distillation column configuration was switched to full discharge.

[0131] Where appropriate, the catalyst is introduced into the reaction medium at the concentration (expressed relative to the total mass of the monomers used) specified in the process stage in Table 1.

[0132] Esterification of the medium was carried out within the time limits shown in Table 1. Water distilled during the test was recovered in a dedicated insulated recovery container.

[0133] Then, the vacuum system is connected to the distillation condenser, and a pressure below atmospheric pressure is applied to the contents of the reactor. Over approximately 30 minutes, the pressure is slowly reduced in stages (approximately 10% to 15% per stage) until it falls below the target value of 10 mbar.

[0134] Once the pressure inside the reaction vessel stabilizes at 5 mbar, the medium continues to react for 3 hours at the jacket temperature specified in Table 1. During this polycondensation step, the stirring speed is reduced to 115 rpm to accommodate the increase in the viscosity of the mixture.

[0135] After the system was restored to atmospheric pressure, the generated PGS was transferred from the reactor vessel to a container and allowed to cool to ambient temperature. The product was then transferred to a freezer for storage, where it remained frozen for at least approximately 24 hours prior to analysis.

[0136] 2- Measurement methods used:

[0137] 2-1 Determination of the microstructure of PGS polymer:

[0138] The microstructure of polymers is achieved through 1 H NMR analysis determined that when 1 When the resolution of H NMR spectroscopy is insufficient to classify and quantify all species, then it is combined with 13 C NMR analysis was performed using a Bruker 500MHz NMR spectrometer, with proton observations at 500.43MHz and carbon observations at 125.83MHz.

[0139] Macroscopic structure and residual monomer content determination of 2-2PGS polymer:

[0140] Size exclusion chromatography (SEC) technology allows for the separation of macromolecules in solution based on their size using columns packed with porous gels. Macromolecules are separated according to their hydrodynamic volume, with the largest molecules eluting first.

[0141] While not an absolute method, SEC allows for the determination of the molar mass distribution of polymers. Various number-average molar masses (Mn) and weight-average molar masses (Mw) can be determined using commercially available standard products, and dispersity can be calculated.

[0142] Size exclusion chromatography was performed using a Viscotek (Malvern Instruments) system equipped with three columns (SDVB, 5 μm, 300 x 7.5 mm, from Polymer Standard Service), one guard column, and three detectors (differential refractometer, differential viscometer, and light scattering detector). One mL of a 5 mg / mL sample solution in THF was filtered through a 0.45 μm PTFE membrane. One hundred μL of this solution was eluted with THF at 0.8 mL / min at 35 °C. Data were acquired and analyzed using OmniSEC software. The number-average molar mass (Mn) and weight-average molar mass (Mw) of the polymer and its dispersion were calculated using calibration curves obtained from Polymer Standard Service (Mainz) with polystyrene standards (Mp: 1306 to 2520000 g / mol).

[0143] The technique used is size exclusion chromatography (SEC), with column configurations optimized for the separation of low-quality species.

[0144] The sample was dissolved in unstabilized THF at a concentration of 1 g / L and injected after stirring for 2 hours.

[0145] The analytical conditions used in this study are described in the table below:

[0146] Elution solution THF without AO Injection volume 100 microliters temperature 35℃ detector Waters RI Flow rate of the mobile phase 1 ml / min column 2 mixed D-pillars + 2 mixed E-pillars

[0147] The calibration used in Moore calculations is PS calibration, covering a range from 2,520,000 to 162 g / mol.

[0148] The calibration used was a hybrid low-weight and medium-weight PS calibration from the PSS standard. The mass range was from 162 to 66,000 g / mol. The calibration was used to determine Mn (g / mol), Mw (g / mol), and... (Mw / Mn) value as PS equivalent:

[0149] The calculation of the macrostructure takes into account regions 1 and 2, and residual monomers are not considered as part of the polymer.

[0150] The sebacic acid content was determined by external calibration.

[0151] The standard range was determined using samples of sebacic acid and glycerol at different concentrations.

[0152] 3-Tests and Results:

[0153] The following table shows the operating conditions of the synthesis process (Table Xa) and the results of the measurements of PGS obtained at the end of these synthesis processes (Table Xb).

[0154] a- PGS synthesis without a catalyst in the presence of water (not in accordance with this invention):

[0155] Table 1a

[0156]

[0157] Table 1b

[0158]

[0159] According to the method carried out in the presence of water and without the use of a catalyst, a reaction time of more than 31 hours is required to reduce the residual monomer content to below 5% and achieve a preferred minimum of approximately 2700 g / mol of Mn. It has been found that by extending the reaction time in this way, both the molar mass dispersion and the content of 1,2,3-triacylglycerol units increase simultaneously.

[0160] b- Synthesis of PGS in the presence of water and TBT (titanium tetrabutyrate) catalyst (not in accordance with this invention):

[0161] In this embodiment, Ti(OBu)4 catalyst was added at a ratio of 2500 ppm (i.e. 0.25% w / w) after the esterification stage and just before the polycondensation step.

[0162] Table 2a

[0163]

[0164]

[0165] Table 2b

[0166]

[0167] It has been found that when a catalyst that does not conform to the present invention but has acceptable toxicological characteristics is introduced at the end of the esterification step (b) and before vacuuming (c), the macrostructure of the resulting PGS deteriorates, with its Mn being lower than that of the polymer obtained without the catalyst and with a similar reaction time (Test 1).

[0168] c- PGS is synthesized in the presence or absence of water and in the presence of a food-grade monobutyltin oxide (or stannic acid) catalyst (FASCAT 9100) added at each step of the method (conforming to and not conforming to this invention).

[0169] In these embodiments, the Fascat 9100 catalyst was added according to the conditions described in the table below.

[0170] Table 3a

[0171]

[0172] Table 3b

[0173]

[0174]

[0175] Tests 5, 9, and 10 conform to the present invention.

[0176] Tests 6, 7, and 8 do not conform to the present invention.

[0177] At the end of the esterification step, the FASCAT9100 catalyst according to the method of the present invention is used, so that the poly(glycerol sebacate) obtained in a time comparable to that of Test 1 without the catalyst has a high number-average molar mass greater than or equal to 2700 g / mol, a controllable dispersion of less than 5, and a low residual monomer content of less than 2% of the polymer weight, and limits the content of 1,2,3-triacylglycerol units to less than 15%.

[0178] Comparing the data from Tests 5 and 6, it was also observed that when the FASCAT9100 catalyst was not introduced into the method according to the invention at the end of the esterification step, the changes in the macrostructural characteristics of the polyester were unfavorable. Its Mn, dispersibility, and 1,2,3-triacylglycerol unit content characteristics all deteriorated, accompanied by gel formation. This led to a decrease in the physicochemical properties of the polymer.

[0179] It was also observed in tests 7 and 8 that when the FASCAT9100 catalyst was not used in the method according to the invention (including contacting the monomers in the presence of water), the dispersibility and 1,2,3-triacylglycerol unit content characteristics of the resulting polyester deteriorated, accompanied by gel formation.

[0180] By comparing the data from Test 2 and Test 10, it was also observed that when the FASCAT9100 catalyst was introduced into the method according to the invention at the end of the esterification step, and the esterification time was shortened to 4 hours (Test 10), the obtained poly(glycerol sebacate) had a high number-average molar mass greater than 2500 g / mol after a total reaction time of less than 10 hours. In the absence of a catalyst (Example 2), this Mn was not reached even after 14 hours. This catalyst can accelerate reaction kinetics while improving the macroscopic structural properties of the polymer.

[0181] d. PGS synthesis in the presence of water and in the presence of a food-grade tris(2-ethylhexanoic acid) monobutyltin catalyst (FASCAT 9102) added in each step of the method (conforming to and not conforming to the present invention).

[0182] In these embodiments, the Fascat 9102 catalyst was added according to the conditions described in the table below.

[0183] Table 4a

[0184]

[0185]

[0186] Table 4b

[0187]

[0188] Test 11 does not conform to the present invention.

[0189] Test 12 conforms to the present invention.

[0190] It has been found that when the catalyst is not introduced into the method according to the invention at the end of the esterification step, the macrostructural properties of the polyester are unfavorable, with lower Mn and higher residual monomer content (Example 11). When the catalyst is introduced into the method according to the invention at the end of the esterification step, the macrostructural properties of the polymer are favorable, with higher Mn and a residual monomer content of less than 5% w / w (Example 12).

Claims

1. A method for preparing a polyester of glycerol and dicarboxylic acid, the method comprising: (a) At a temperature below 100°C, a monomer comprising at least glycerol and the corresponding dicarboxylic acid is contacted in the presence of water, wherein the molar ratio of glycerol / dicarboxylic acid ranges from 0.5 / 1 to 10 / 1. (b) Esterification is carried out in an inert atmosphere at a temperature above 110°C, preferably in the range of 130°C to 180°C; (c) At a temperature above 110°C, preferably in the range of 130°C to 180°C, the reaction medium is evacuated to a pressure below 100 mbar, preferably below 50 mbar, and preferably below 10 mbar. (d) Maintain a vacuum and a temperature above 110°C, preferably in the range of 130°C to 180°C, to carry out polycondensation; The method includes introducing a polycondensation catalyst at the end of esterification in step (b), before or after vacuuming in step (c), in an amount less than or equal to 5000 ppm relative to the total weight of the monomers, wherein the catalyst is a tin-based food-grade catalyst selected from organotin compounds containing a carboxyl functional group (-C(O)OH), organotin compounds containing a functional group (-Sn(O)OH), and tris(2-ethylhexanoic acid) monobutyltin.

2. The method according to the preceding claim, wherein, The dicarboxylic acid has the formula [HOOC-(CH2)] n -COOH], where n is a number from 1 to 30, preferably a number from 1 to 10.

3. The method according to any one of the preceding claims, wherein, The dicarboxylic acid is sebacate.

4. The method according to any one of the preceding claims, wherein, The molar ratio of glycerol to dicarboxylic acid ranges from 0.9 / 1 to 2 / 1, preferably from 1 / 1 to 1.5 / 1.

5. The method according to any one of the preceding claims, wherein, The contact of monomers is achieved by introducing dicarboxylic acid monomers into a mixture containing glycerol monomers and water.

6. The method according to any one of the preceding claims, wherein, The diacid monomer is introduced in solid form into a mixture containing glycerol monomer and water, and after the monomer contact in step (a), the diacid monomer is melted in an aqueous medium.

7. The method according to any one of the preceding claims, wherein, When the monomer contact in step (a) ends, the reaction medium is refluxed.

8. The method according to any one of the preceding claims, wherein, The method includes, at the end of step (a), removing the water introduced to contact the monomer, preferably by distillation.

9. The method according to any one of the preceding claims, wherein, The method includes a water removal step, preferably by distillation, which is performed after or simultaneously with the esterification step (b), the polycondensation step (c), or the esterification step (b) and the polycondensation step (c).

10. The method according to any one of the preceding claims, wherein, The tin-based food-grade catalyst is selected from food-grade alkyltin compounds, which contain a carboxyl functional group (-C(O)OH) or a functional group (-Sn(O)OH), and the alkyl group has 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms.

11. The method according to any one of claims 1 to 9, wherein, The tin-based food-grade catalyst is selected from food-grade monobutyltin oxide (or stannic acid) and food-grade tri(2-ethylhexanoic acid) monobutyltin.

12. The method according to any one of the preceding claims, wherein, The tin-based food-grade catalyst is food-grade monobutyltin oxide (or stannic acid).

13. The method according to any one of the preceding claims, wherein, The amount of catalyst introduced is less than or equal to 3000 ppm.

14. A polyester of glycerol and dicarboxylic acid, comprising: - Residual monomer content of less than 5% by weight based on polymer weight; - Number-average molar mass Mn greater than 2500 g / mol, preferably greater than or equal to 2700 g / mol; - A dispersion of less than or equal to 10, preferably less than or equal to 5. - Less than 15 mol% of 1,2,3-triacylglycerol units relative to all units of the polymer.

15. The polyester of glycerol and dicarboxylic acid according to the preceding claim, wherein the number-average molar mass Mn is less than 3500 g / mol, preferably less than 3000 g / mol.

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