Polyesteramide polymers

Abstract

The invention provides a water-soluble biodegradable polyesteramide polymer and a preparation method of the water-soluble biodegradable polyesteramide polymer. The polyesteramide has a good balance of crystallinity, water solubility, thermal and mechanical properties and biodegradability and is a promising polymer for industrialization.

Description

Related applications

[0001] This application claims priority to Indian Provisional Application 202311058192, filed on August 30, 2023, and European Patent Application 23203689.7, filed on October 16, 2023, the entire contents of each of these applications are incorporated herein by reference for all purposes. Technical Field

[0002] This invention provides a water-soluble, biodegradable polyesteramide polymer. Background Technology

[0003] Poly(esteramide) (PEA) is a very important synthetic polymer with applications in many fields. The combination of the thermal and mechanical properties of polyamides with the biocompatibility and biodegradability of polyesters has yielded promising biomaterials.

[0004] PEAs derived from amino acids, diols, and dicarboxylic acids have been investigated for biomedical applications because they offer the advantages of both natural and synthetic polymers. The incorporated amino acids can be recognized by biological systems, and their enzymatic biodegradation leads to metabolically degradable building blocks. Furthermore, the properties of these PEAs can be readily modulated by altering their monomer composition.

[0005] Various types of PEA are synthesized primarily through three different methods: melt polycondensation (MP), interfacial polycondensation (IP), and solution polymerization (SP). Of these methods, melt polycondensation is advantageous from an industrial perspective because the polymer does not require cumbersome post-polymerization treatments and does not use harmful organic solvents. However, the MP method presents challenges in terms of proper monomer selection, high-temperature stability of the monomers, and minimizing undesirable side reactions during high-temperature and vacuum processes. Therefore, the choice of monomers is very limited.

[0006] Polymer Degradation and Stability 181 (2020)109323 teaches the synthesis and characterization of PEAs based on amino acid, diol, and dicarboxylic acid monomers through different methods. However, water solubility is not specifically mentioned in this article.

[0007] J. Mater. Sci. Mater. Med. 22 (2011) 469-479 reports a water-soluble arginine-based poly(ester amide) with ionic charges (Arg-PEA), which is composed of three non-toxic building blocks: L-arginine, diols and dicarboxylic acids. It was found that Arg-PEA has good solubility in water and many other polar solvents. However, if only water-solubility is tuned, some other properties such as mechanical and thermal properties and biodegradability cannot be well balanced. The obtained Arg-PEA has cationic properties.

[0008] Without wishing to be bound by any particular theory, the selected monomers can well tune the hydrophilic-lipophilic balance (HLB) and thus the water-soluble biodegradable poly(ester amide) of the present invention has a good balance of crystallinity, water-solubility, mechanical and thermal properties and biodegradability.

[0009] Furthermore, the water-soluble biodegradable poly(ester amide) of the present invention has anionic properties, which can be used in many applications such as agrochemical formulations.

[0010] Moreover, the poly(ester amide) of the present invention can be easily prepared by melt polycondensation (MP) and thus is a promising polymer for industrialization.

[0011] In another aspect of the present invention, a method for synthesizing a poly(ester amide) polymer is provided.

[0012] Finally, the present invention also relates to the use of a given poly(ester amide) polymer as a dispersant for active ingredients. BRIEF DESCRIPTION OF DRAWINGS

[0013] Figure 1 . Typical 1H-NMR of the Example 4 polymer in DMSO-d6 at room temperature. 1 H-NMR showing characteristic peaks of different protons;

[0014] Figure 2 . Typical 1H-NMR of the Example 4 polymer in DMSO-d6 at room temperature. 13 C-NMR showing characteristic peaks of different carbons;

[0015] Figure 3 . Thermogravimetric analysis (TGA) plot of the Example 4 polymer.

[0016] Figure 4 . Differential scanning calorimetry (DSC) of the Example 4 polymer for the second heating cycle. DETAILED DESCRIPTION

[0017] The polyester amide polymer of the present invention is prepared by polycondensation of at least the following monomers (a) to (d):

[0018] (a) an aliphatic / aromatic unsulfonated dicarboxylic acid / ester of a dicarboxylic acid;

[0019] (b) an aliphatic diol;

[0020] (c) an aliphatic / aromatic sulfonated dicarboxylic acid / ester of a dicarboxylic acid;

[0021] (d) a compound comprising two ester functions and two amide functions [DEDA].

[0022] The aliphatic unsulfonated dicarboxylic acid / ester of a dicarboxylic acid according to the present invention can be linear or cyclic. Preferred linear aliphatic unsulfonated dicarboxylic acid / ester of a dicarboxylic acid according to the present invention is an alkyl dicarboxylic acid / ester of a dicarboxylic acid having the formula ROOC-(CH2)n-COOR (I) with n = 2-4 and R being H, a Ci to Cs alkyl group or a phenyl group. Preferred cycloaliphatic unsulfonated dicarboxylic acid / ester of a dicarboxylic acid according to the present invention is based on a ring having 5 or 6 carbon atoms, i.e. an alkyl ester of a cyclopentane dicarboxylic acid / cyclopentane dicarboxylic acid or an alkyl ester of a cyclohexane dicarboxylic acid / cyclohexane dicarboxylic acid, in particular 1,2-cyclopentane dicarboxylic acid, 1,3-cyclopentane dicarboxylic acid, 1,3-cyclohexane dicarboxylic acid or 1,4-cyclohexane dicarboxylic acid and their corresponding alkyl esters, wherein the alkyl group can vary from a methyl group to an octyl group or can be a phenyl group. n -COOR (I) with n = 2-4 and R being H, a Ci to Cs alkyl group or a phenyl group. Preferred cycloaliphatic unsulfonated dicarboxylic acid / ester of a dicarboxylic acid according to the present invention is based on a ring having 5 or 6 carbon atoms, i.e. an alkyl ester of a cyclopentane dicarboxylic acid / cyclopentane dicarboxylic acid or an alkyl ester of a cyclohexane dicarboxylic acid / cyclohexane dicarboxylic acid, in particular 1,2-cyclopentane dicarboxylic acid, 1,3-cyclopentane dicarboxylic acid, 1,3-cyclohexane dicarboxylic acid or 1,4-cyclohexane dicarboxylic acid and their corresponding alkyl esters, wherein the alkyl group can vary from a methyl group to an octyl group or can be a phenyl group.

[0023] Preferred aromatic unsulfonated dicarboxylic acid / ester of a dicarboxylic acid according to the present invention is an alkyl ester of a terephthalic acid / terephthalic acid and an alkyl ester of a isophthalic acid / isophthalic acid, wherein the alkyl group can vary from a methyl group to an octyl group or can be a phenyl group.

[0024] The aliphatic / aromatic unsulfonated dicarboxylic acid / ester of a dicarboxylic acid of the present invention is preferably an aliphatic unsulfonated dicarboxylic acid / ester of a dicarboxylic acid, more preferably a cyclohexane derivative. In particular 1,4-cyclohexane dicarboxylic acid (CHDA) gave good results in the framework of the present invention.

[0025] The aliphatic diol used for the present invention can be a linear aliphatic diol selected from the group consisting of alkyl diols like ethylene glycol or propylene glycol, diethylene glycol, triethylene glycol or polyethylene glycol with a number of ethylene oxide in the range of 4 to 75. Alternatively, it can be a cyclic saturated diol, preferably comprising 5 or 6 C atoms, i.e. a cyclopentane diol or a cyclohexane diol, in particular 1,2-cyclopentane diol, 1,3-cyclopentane diol, 1,3-cyclohexane diol or 1,4-cyclohexane diol.

[0026] Preferably, a linear aliphatic diol, more preferably an alkyl diol, in particular ethylene glycol (EG) is used.

[0027] As mentioned previously, the polyester amide polymers of the present application have anionic properties which can come from any of the anions contained in the polymer, in particular one or more sulfonate anions of monomer (c).

[0028] Aliphatic / aromatic sulfonated dicarboxylic acid / ester of dicarboxylic acid has at least one sulfonic acid group, preferably in the form of an alkali metal (preferably sodium) sulfonate, and two acid / ester functions attached to one or more aromatic rings (when referring to aromatic dicarboxylic acid or alkyl diester thereof), or to an aliphatic chain (when referring to aliphatic dicarboxylic acid / alkyl diester of aliphatic dicarboxylic acid), wherein the alkyl group can vary from a methyl to an octyl group, or can be a phenyl group.

[0029] Aromatic sulfonated dicarboxylic acid / ester of dicarboxylic acid monomers that can be used in the framework of the present application are preferably isophthalic acid / ester of isophthalic acid, terephthalic acid / ester of terephthalic acid and naphthalene dicarboxylic acid / ester of naphthalene dicarboxylic acid. Preferred are 2-sodium sulfoisophthalic acid / ester of 2-sodium sulfoisophthalic acid, 4-sodium sulfoisophthalic acid / ester of 4-sodium sulfoisophthalic acid, 5-sodium sulfoisophthalic acid / ester of 5-sodium sulfoisophthalic acid, 2-sodium sulfoisophthalic acid / ester of 2-sodium sulfoisophthalic acid, 2,6-dicarboxynaphthalene-4-sodium sulfonic acid / ester of 2,6-dicarboxynaphthalene-4-sodium sulfonic acid and 2,6-dicarboxynaphthalene-7-sodium sulfonic acid / ester of 2,6-dicarboxynaphthalene-7-sodium sulfonic acid. Aliphatic sulfonated dicarboxylic acid / ester of dicarboxylic acid that can be used in the framework of the present application is sodium sulfo succinate dialkyl ester.

[0030] Preferably, aromatic sulfonated dicarboxylic acid / ester of dicarboxylic acid monomers, more preferably 5-sodium sulfoisophthalic acid / ester of 5-sodium sulfoisophthalic acid, in particular 5-sodium sulfoisophthalic acid (SSIA) are used in the framework of the present application.

[0031] Preferably, the compound [DEDA] used in the present application comprising two amide functional groups and two ester functional groups is a compound having the general formula (II):

[0032] (II)

[0033] wherein:

[0034] - R1 is an arylene group, an alkylenediyl group or a cycloalkylenediyl group;

[0035] -R2 and R3 may be the same as or different from each other, and are hydrogen, or straight-chain, branched, or cyclic hydrocarbon groups, which may optionally have one or more heteroatoms inserted and / or be optionally substituted by one or more functional groups; and

[0036] -R4 and R5 may be the same as or different from each other, and are alkyl groups.

[0037] "Arenediyl" refers to a divalent group obtained by removing a hydrogen atom from each of the two carbon atoms in the aromatic ring of an aromatic hydrocarbon, including but not limited to phenylene and furanyl groups. Arenediyl groups include substituted or unsubstituted arenediyl groups. Arenediyl groups may have one, two, three, or four independent substituents selected from the group consisting of: alkyl, alkenyl, alkynyl, alkoxy, alkylated amino, carboxyl, ester, cyano, nitro, and halogen.

[0038] "alkanediyl" refers to a divalent group obtained by removing two hydrogen atoms attached to one or two carbon atoms of an alkane, especially C1-C. 20 Alkyl groups. Alkyl groups include substituted or unsubstituted alkyl groups.

[0039] "Cycloalkanediyl" refers to a divalent group obtained by removing two hydrogen atoms attached to one or two carbon atoms of a cycloalkane, including but not limited to cyclohexanediyl. Cycloalkanediyl includes substituted or unsubstituted alkyldiyl groups.

[0040] The functional groups optionally substituted on R2 or R3 can be selected from the group consisting of: alkyl, alkenyl, alkynyl, alkoxy, alkylated amino, carboxyl, ester, cyano, nitro and halogen.

[0041] The optional heteroatom in R2 or R3 can be O, S, N, F, Cl, or Br.

[0042] Preferably, R2 and R3 are the same or different from each other, and are hydrogen, or straight-chain or branched hydrocarbon groups, more preferably hydrogen or straight-chain or branched alkyl groups, especially straight-chain or branched C1-C. 10 Alkyl groups, such as methyl, ethyl, propyl, isopropyl, isobutyl, sec-butyl, and tert-butyl.

[0043] In some preferred embodiments, R2 and R3 are the same.

[0044] R4 and R5 can be straight-chain or branched alkyl groups. Preferably, R4 and R5 are the same as or different from each other, and are C16-264 ... 1- C 10 Alkyl, more preferably C 1- C5 alkyl.

[0045] In some preferred embodiments, R4 and R5 are the same.

[0046] In a preferred embodiment, the polyesteramide polymer of the present application is prepared by polycondensation of the following monomers (a) to (d):

[0047] (a) an aliphatic, non-sulfonated dicarboxylic acid / ester of a dicarboxylic acid, preferably a cyclohexane derivative, in particular 1,4-cyclohexanedicarboxylic acid (CHDA);

[0048] (b) a linear aliphatic diol, in particular ethylene glycol (EG);

[0049] (c) an aromatic, sulfonated dicarboxylic acid / ester of a dicarboxylic acid, preferably 5-sodium sulfoisophthalic acid / ester of a dicarboxylic acid, in particular 5-sodium sulfoisophthalic acid (SSIA);

[0050] (d) a compound having the general formula (II);

[0051] wherein:

[0052] - R1 is a cycloalkanediyl, in particular cyclohexanediyl;

[0053] - R2 and R3 are hydrogen, or a linear or branched C1-C5 alkyl group, such as methyl, ethyl, propyl, isopropyl, isobutyl, sec-butyl and tert-butyl; and 10 - R4 and R5 are C1-C5 alkyl groups.

[0054] - R4 and R5 are C1-C5 alkyl groups.

[0055] In a preferred embodiment, the polyesteramide polymer of the present application is prepared by polycondensation of the following monomers (a) to (d):

[0056] (a) 1,4-cyclohexanedicarboxylic acid (CHDA);

[0057] (b) ethylene glycol (EG);

[0058] (c) 5-sodium sulfoisophthalic acid (SSIA);

[0059] (d) DEDA having formula (III) (hereinafter "CY-GLA"):

[0060] (III).

[0061] In a preferred embodiment, the polyesteramide polymer of the present application is prepared by polycondensation of the following monomers (a) to (d):

[0062] (a) an aliphatic, non-sulfonated dicarboxylic acid / ester of a dicarboxylic acid, preferably a cyclohexane derivative, in particular 1,4-cyclohexanedicarboxylic acid (CHDA);

[0063] (b) linear aliphatic diols, in particular ethylene glycol (EG);

[0064] (c) aromatic sulfonated dicarboxylic acids / esters of dicarboxylic acids, preferably 5-sodiosulfoisophthalic acid / esters of 5-sodiosulfoisophthalic acid, in particular 5-sodiosulfoisophthalic acid (SSIA);

[0065] (d) compounds having the general formula (II);

[0066] wherein:

[0067] - R1is an arylene group, in particular phenylene, furanylene;

[0068] - R2and R3are hydrogen, or linear or branched C1-C4alkyl; 10 alkyl groups such as methyl, ethyl, propyl, isopropyl, isobutyl, sec-butyl and tert-butyl; and

[0069] - R4and R5are C1-C5alkyl groups.

[0070] When R1is furanylene, the monomers are preferably derived from bio-based furandicarboxylic acid and amino acids. The present applicant has now found that such readily available monomers can provide the water-soluble biodegradable polyesters of the present application with high thermal and mechanical stability, heteroaromatic furan building units and biodegradability.

[0071] A particularly preferred polyesteramide of the present application is prepared by polycondensation of the following monomers (a) to (d):

[0072] (a) 1,4-cyclohexanedicarboxylic acid (CHDA);

[0073] (b) ethylene glycol (EG);

[0074] (c) 5-sodiosulfoisophthalic acid (SSIA);

[0075] (d) DEDA having formula (IV) (hereinafter “FU-GLA”):

[0076] (IV).

[0077] A particularly preferred polyesteramide of the present application is prepared by polycondensation of the following monomers (a) to (d):

[0078] (a) 1,4-cyclohexanedicarboxylic acid (CHDA);

[0079] (b) ethylene glycol (EG);

[0080] (c) 5-sodiosulfoisophthalic acid (SSIA);

[0081] (d) DEDA having formula (V) (hereinafter "TE-GLA"):

[0082] (V).

[0083] In a preferred embodiment, the polyesteramide polymer of the present application is prepared by polycondensation of the following monomers (a) to (d):

[0084] (a) an aliphatic, non-sulfonated dicarboxylic acid / ester of a dicarboxylic acid, preferably a cyclohexane derivative, in particular 1,4-cyclohexanedicarboxylic acid (CHDA);

[0085] (b) a linear aliphatic diol, in particular ethylene glycol (EG);

[0086] (c) an aromatic, sulfonated dicarboxylic acid / ester of a dicarboxylic acid, preferably 5-sodium sulfoisophthalic acid / ester of a dicarboxylic acid, in particular 5-sodium sulfoisophthalic acid (SSIA);

[0087] (d) a compound having general formula (II);

[0088] wherein:

[0089] - R1 is an alkanediyl, in particular a C1-C5 alkanediyl; 20 alkanediyl;

[0090] - R2 and R3 are hydrogen, or a linear or branched C1-C5 alkyl group, such as methyl, ethyl, propyl, isopropyl, isobutyl, sec-butyl and tert-butyl; and 10

[0091] - R4 and R5 are C1-C5 alkyl groups.

[0092] A particularly preferred polyesteramide of the present application is prepared by polycondensation of the following monomers (a) to (d):

[0093] (a) 1,4-cyclohexanedicarboxylic acid (CHDA);

[0094] (b) ethylene glycol (EG);

[0095] (c) 5-sodium sulfoisophthalic acid (SSIA);

[0096] (d) DEDA having formula (VI) (hereinafter "SU-GLA"):

[0097] (VI).

[0098] ​The present invention also relates to a novel and inventive polyester amide polymer comprising the following repeating units: CHDA-EG, SSIA-EG and DEDA-EG (e.g. FU-GLA-EG, CY-GLA-EG, TE-GLA-EG and SU-GLA-EG).

[0099] Advantageously, the ratio of the number of moles of monomer (b) to the total number of moles of monomers (a), (c) and (d) in the polymer backbone is about 1 : 1, for example 0.8 to 1.2, preferably 0.9 to 1.1. Thus, the polyester amide polymer of the present invention is preferably derived from a reaction mixture in which the total mole percentage of monomers (a), (c) and (d) is 50% based on the total number of moles of monomers (a), (b), (c) and (d). In particular, monomer (c) has a mole percentage of 0.01 to 10 mol% and monomer (d) has a mole percentage of 0.01 to 25 mol% based on the total number of moles of monomers (a), (b), (c) and (d). The amount of monomer (a) can be adjusted to achieve a total mole percentage of 50%. Thus, monomer (a) preferably has a mole percentage of 15 to 49.98 mol%.

[0100] The skilled person will appreciate that an excess of monomer (b) can be present in the reaction mixture when monomer (b) is also used as a solvent for the solid reactants. The excess of monomer (b) can be added at the start of the polymerisation reaction or during the polymerisation reaction. In preferred embodiments, the polymerisation can be carried out with a mixture in which the ratio of the number of moles of monomer (b) to the total number of moles of monomers (a), (c) and (d) is about 1 : 1 to 6 : 1 and more preferably 3 : 1 to 5 : 1.

[0101] The weight average molecular weight of the polyester amide can vary from 5000 to 30000 g / mol.

[0102] The preferred polyester amides according to the present invention comprise 15-30 mol% of aromatic moieties (e.g. SSIA and DEDA comprising aromatic rings) in order to promote / facilitate biodegradability.

[0103] The polyester amide polymers of the present invention have a solubility in distilled water at room temperature of at least 1 wt%, preferably at least 1.5 wt%, more preferably at least 5 wt%.

[0104] The present application also relates to a process for the synthesis of the above-mentioned polyester amide polymer by polycondensation of the monomers (a), (b), (c) and (d), preferably in the presence of a catalyst. The catalyst is preferably a hydrolysis-stable catalyst, more preferably selected from the group consisting of chelates of titanium or zirconium salts derived from ethanolamine, alone and / or mixtures or solutions thereof. In particular, titanium (IV) isopropoxide (triethanolaminate) gives good results. This compound is available under the trade name Tyzor® TE as an 80 wt% solution in isopropyl alcohol.

[0105] The polycondensation according to the present application is preferably started on a mixture of all monomers (a) to (d), i.e. first the monomers (a), (b), (c) and (d) are mixed and then reacted by polycondensation, preferably by increasing the temperature and / or reducing the pressure. Alternatively, the polycondensation can be started on a mixture of only some monomers, the other monomers being introduced in a delayed manner. Yet another possibility is to prepare two or more prepolymers by polycondensation and then to perform a transesterification of the prepolymers.

[0106] In a preferred embodiment, the procedure for preparing the polyester amide according to the present application is as follows. First, all monomers are mixed in a reaction vessel and the mixture is heated from about 110 °C to 200 °C, preferably from 120 °C to 180 °C under nitrogen protection. The reaction mixture is then preferably kept under stirring at the same temperature for 30 to 240 minutes, preferably 60 to 180 minutes. Subsequently, the reaction temperature is preferably increased to 200 °C and a reduced pressure of 50 to 300 mbar, preferably 100 to 200 mbar is gradually reached; under this condition, the diol (e.g. ethylene glycol) starts to distill and is preferably collected in a receiver. The reaction temperature is then preferably increased to between about 210 °C and 250 °C under reduced pressure. When the reaction reaches the desired temperature, the pressure is then preferably further reduced to about 10 to 50 mbar, preferably to about 20 to 40 mbar. The reaction is then preferably kept under this condition for 30 to 240 minutes, preferably 60 to 180 minutes, after which the polymer can be discharged in the hot state.

[0107] The present application also relates to the use of a given polyester amide polymer as a dispersant for active ingredients. Examples

[0108] Materials

[0109] - 2,5-furandicarboxylic acid (CAS number: 3238-40-2), TCI Chemicals (India);

[0110] - 1,4-cyclohexanedicarboxylic acid (CAS Number: 1076-97-7), Sigma-Aldrich;

[0111] - thionyl chloride (CAS Number: 7719-09-7), SD fine-chem;

[0112] - anhydrous N,N-dimethylformamide (CAS Number: 68-12-2), Sigma-Aldrich;

[0113] - glycine methyl ester hydrochloride (CAS Number: 5680-79-5), Tokyo Chemical Industry Co., Ltd. (TCI);

[0114] - anhydrous dichloromethane (CAS Number: 75-09-2), Sigma-Aldrich;

[0115] - triethylamine (CAS Number: 121-44-8), Sigma-Aldrich;

[0116] - 5-sodium sulfoisophthalic acid (CAS Number: 6362-79-4), Sigma-Aldrich;

[0117] - ethylene glycol (CAS Number: 107-21-1), SD fine-chem;

[0118] - Tyzor® TE organotitanate (CAS Number: 74665-17-1), Sigma-Aldrich.

[0119] Diacid to diacid chloride (2,5-furandicarboxylic acid dichloride)

[0120] A two-necked 250 mL round bottom flask was equipped with a condenser, magnetic stirrer, and an oil bath. The required amount of 2,5-furandicarboxylic acid was charged into the reaction vessel and purged twice with N2 gas. Next, freshly distilled SOCl2 (10 equivalents) and a catalytic amount of anhydrous DMF (0.04 equivalents) were introduced into the reactor and the mixture was refluxed at 80 °C for 5 h under constant stirring. The condenser was connected to a washing bottle filled with a concentrated aqueous sodium hydroxide (NaOH) solution (minimum two in series). After the reaction, the excess SOCl2 and DMF were removed under vacuum at room temperature and collected in a trap cooled with dry ice and acetone. After removal of most of the liquid, the reaction mass was further dried under high vacuum at 55 °C for 2 h followed by drying at room temperature for 4 h. The product was stored under inert atmosphere and used for the next step without further purification.

[0121] Diacid to diacid chloride (1,4-cyclohexanedicarboxylic acid dichloride)

[0122] A two-necked 250 mL round bottom flask was equipped with a condenser, magnetic stirrer, and an oil bath. The required amount of 1,4-cyclohexanedicarboxylic acid was charged into the reaction vessel and purged twice with N2 gas. Next, freshly distilled SOCl2 (10 equivalents) and a catalytic amount of anhydrous DMF (0.05 equivalents) were introduced into the reactor and the mixture was refluxed at 80 °C for 6 h under constant stirring. The condenser was connected to a washing bottle filled with concentrated aqueous sodium hydroxide (NaOH) solution (minimum two in series). After the reaction, the excess SOCl2 and DMF were removed under vacuum at room temperature and collected in a trap cooled with dry ice and acetone. After removal of most of the liquid, the reaction mass was further dried under high vacuum at 60 °C for 2 h followed by drying at room temperature for 5 h. The product was stored under inert atmosphere and used for the next step without further purification.

[0123] Diacid chloride to DEDA monomer (FU-GLA)

[0124] A two-necked 1 L RB flask was equipped with a condenser, magnetic stirrer, and a dropping funnel. The reactor was purged twice with inert gas, solid glycine methyl ester hydrochloride (2.1 equivalents) and anhydrous dichloromethane (DCM) (3.0 mL / mmol of methyl ester) were charged into the reactor. The reaction mixture was stirred vigorously at 0-5 °C followed by drop-wise addition of Et3N (5 equivalents) to the reaction mixture. After a few minutes, a solution of prepared 2,5-furandicarboxylic acid dichloride (1 equivalent) in anhydrous DCM (0.5 mL / mmol of diacid chloride) was slowly added to the reaction mixture over a period of 45 min. Finally, the reaction mixture was stirred at room temperature overnight. The insoluble white precipitate was removed by filtration and the solution was dried under a rotary evaporator at 45 °C. The crude mixture was re-dissolved in excess CHCI3 and cooled to -5 °C. After 1 h, the insoluble precipitate was again removed by filtration and the solution was washed with 3% NaHCO3 and distilled water. The organic layer was dried over Na2SO4, concentrated by a rotary evaporator and added drop-wise to excess n-hexane (about 5-6 folds) to get the target product. Finally, the product was dried under vacuum at 60 °C for a few hours. The FU-GLA product was characterized by1H NMR, LC-MS, TGA, DSC, and elemental analysis. 1 H / 13 The FU-GLA product was characterized by1H NMR, LC-MS, TGA, DSC, and elemental analysis.

[0125]

[0126] FU-GLA

[0127] Diacid chloride to DEDA monomer (CY-GLA)

[0128] A two-necked 1 L RB flask was equipped with a condenser, magnetic stirrer and dropping funnel. The reactor was purged twice with inert gas, the reactor was charged with solid glycine methyl ester hydrochloride (2.1 eq) and anhydrous dichloromethane (DCM) (3.0 mL / mmol of methyl ester). The reaction mixture was stirred vigorously at 0°C-5°C, followed by dropwise addition of Et3N (5 eq) to the reaction mixture. After a few minutes, a solution of prepared 1,4-cyclohexanedicarboxylic acid dichloride (1 eq) in anhydrous DCM (0.5 mL / mmol of diacid chloride) was slowly added to the reaction mixture over a period of 45 min. Finally, the reaction mixture was stirred at room temperature overnight. The insoluble white precipitate was removed by filtration and washed repeatedly by distilled water to remove the triethylamine hydrochloride generated during the reaction. Finally, the product was dried under vacuum at 60°C for several hours. The CY-GLA product was characterized by 1 H / 13 C NMR, LC-MS, TGA and DSC were performed on CY-GLA product.

[0129]

[0130] CY-GLA

[0131] Examples 1-2: Polyester amide polymers with different DEDA monomers: synthesis and properties

[0132] General polymerization procedure for Examples 1-2

[0133] The desired amount of 1,4-cyclohexanedicarboxylic acid (CHDA), 5-sodiosulfoisophthalic acid (SSIA), DEDA, diol, and Tyzor® TE (catalyst) were mixed in a glass reactor under atmospheric pressure and N2 flow. The polymerization reaction was started by heating the reaction mixture at 160°C for 1 h under N2 flow, during which the reaction mixture gradually became completely soluble. Next, the reaction temperature was increased to 200°C, the N2 flow was stopped and vacuum was slowly applied until 100 mbar was reached. Finally, the temperature was increased in the range of 225-235°C and the vacuum was gradually decreased until 5-10 mbar was reached and the polymerization was continued for 1-2 h more to remove excess EG and increase the molecular weight (Mw) of the PEA. The final polymer was collected from the glass reactor immediately after the reaction, as it was very difficult to collect once cooled to room temperature.

[0134] Table 1

[0135]

[0136] Examples 3-7: Polyester amide polymers with FU-GLA monomers: synthesis and properties

[0137] Examples 3 to 7 with different molar ratios of CHDA, SSIA, FU-GLA and EG were prepared according to the protocol of Examples 1 to 2. The characteristics / properties are listed in Table 2 below.

[0138]

[0139] PEAs of Examples 3 to 7 are a very interesting class of water-soluble polymers with a variety of functional moieties like hydrophobic, ionic (anionic nature), hydrophilic and heteroaromatic functional moieties. As shown by the test results in Table 2, a good balance of crystallinity, water-solubility, thermal and mechanical properties as well as biodegradability was obtained.

[0140]

[0141] Gel Permeation Chromatography (GPC)

[0142] Molecular weights were measured by Gel Permeation Chromatography (GPC) in a WATERS 515 HPLC pump, Shodex-101 RI detector and two HFIP gel columns with guard columns at a flow rate of 0.4 ml / min. PMMA was used as standard, PET as reference standard and 0.05 M potassium trifluoroacetate in hexafluoroisopropanol (HFIP) as mobile phase.

[0143] Thermogravimetric Analysis (TGA)

[0144] TGA was measured in a TA instrument (TGA Q500) at a heating rate of 20 °C / min from room temperature up to 800 °C. The decomposition temperature (Td) mentioned here is the 10% decomposition of the initial sample weight.

[0145] Differential Scanning Calorimetry (DSC)

[0146] Glass transition temperature (Tg) was measured in a TA instrument (DSC Q2000) with two cycles of cooling and heating in the range of -50 °C to 200 °C at a heating rate of 10 °C / min. The Tg reported in the present report is estimated from the second heating cycle. Due to the incorporation of both amide and furan groups, the Tg increases significantly with increasing amount of FU-GLA monomer. Furthermore, when SSIA is incorporated into the polymer backbone, the Tg also increases due to the increase in aromatic groups. Thus, the thermal as well as mechanical properties of PEA can be easily tuned by careful variation of the monomer units.

[0147] Water-solubility test results

[0148] In this test, the polymers obtained by Examples 3 to 6 (with 5-10 mol% of SSIA) were well soluble in distilled water at least in the range of 1-5 wt%. The polymer obtained by Example 7 (without SSIA) was not soluble in water.

[0149] Biodegradability test results

[0150] The biodegradability test was performed according to: OECD (1992), Test No. 302B: Inherent Biodegradability: Zahn-Wellens / EVPA Test, OECD Guidelines for the Testing of Chemicals, Section 3, OECD Publishing, Paris [OECD (1992) Test No. 302B: Inherent Biodegradability: Zahn-Wellens / EVPA Test, OECD Guidelines for the Testing of Chemicals, Section 3, OECD Publishing, Paris], the content of which is incorporated herein by reference.

[0151] In this test, a mixture containing the test substance, mineral nutrients, and a relatively large amount of activated sludge in aqueous medium is stirred and aerated in the dark or in diffuse light at 20-25 °C for up to 28 days. A blank control containing activated sludge and mineral nutrients but no test substance is run in parallel. The biodegradation process is monitored by determining the DOC (or COD) in filtered samples taken daily or at other time intervals. After each time interval, the ratio of the eliminated DOC (or COD) corrected against the blank to the initial DOC (or COD) value is expressed as the percentage biodegradation at the time of sampling. The percentage biodegradation is plotted against time to give a biodegradation curve.

[0152] Water-soluble PEA containing FU-GLA was tested and was inherently biodegradable in the range of 87-98% within 28 days (Table 2). Interestingly, the biodegradability was not affected by the increase in the amount of amide-containing DEDA monomers in the range of 5-20 mol%.

Claims

1. A polyesteramide polymer prepared by polycondensation of at least the following monomers (a) to (d): (a) Aliphatic / aromatic unsulfonated dicarboxylic acids / esters of dicarboxylic acids; (b) Aliphatic diols; (c) Aliphatic / aromatic sulfonated dicarboxylic acids / esters of dicarboxylic acids; and (d) Compounds containing two ester functional groups and two amide functional groups [DEDA].

2. The polyesteramide polymer according to claim 1, wherein, The aliphatic / aromatic non-sulfonated dicarboxylic acid / dicarboxylic acid ester is selected from: - Possesses the formula ROOC-(CH2) n -COOR (I) alkyl dicarboxylic acid / ester of alkyl dicarboxylic acid, wherein n = 2-4, and R is H, C1 to C8 alkyl or phenyl; - Alkyl esters of cyclopentanedicarboxylic acid / cyclopentanedicarboxylic acid or alkyl esters of cyclohexanedicarboxylic acid / cyclohexanedicarboxylic acid, especially 1,2-cyclopentanedicarboxylic acid, 1,3-cyclopentanedicarboxylic acid, 1,3-cyclohexanedicarboxylic acid or 1,4-cyclohexanedicarboxylic acid and their corresponding alkyl esters, wherein the alkyl group may vary from methyl to octyl, or may be phenyl; - Alkyl esters of terephthalic acid / terephthalic acid and alkyl esters of isophthalic acid / isophthalic acid, wherein the alkyl group can vary from methyl to octyl, or can be phenyl.

3. The polyesteramide polymer according to claim 1 or 2, wherein, The aliphatic / aromatic unsulfonated dicarboxylic acid / dicarboxylic acid ester is an aliphatic unsulfonated dicarboxylic acid / dicarboxylic acid ester, preferably a cyclohexane derivative, especially 1,4-cyclohexanedicarboxylic acid (CHDA).

4. The polyesteramide polymer according to any one of claims 1 to 3, wherein, This aliphatic diol is selected from: - Alkyl glycols, such as ethylene glycol or propylene glycol, diethylene glycol, triethylene glycol; polyethylene glycols with an ethylene oxide number ranging from 4 to 75; - Cyclic saturated diols, preferably cyclopentanediol or cyclohexanediol, especially 1,2-cyclopentanediol, 1,3-cyclopentanediol, 1,3-cyclohexanediol or 1,4-cyclohexanediol.

5. The polyesteramide polymer according to claim 4, wherein, The aliphatic diol (b) is an alkyl diol, particularly ethylene glycol (EG).

6. The polyesteramide polymer according to any one of claims 1 to 5, wherein, The aliphatic / aromatic sulfonated dicarboxylic acid / dicarboxylic acid ester is selected from: - Esters of isophthalic acid / isophthalic acid, esters of terephthalic acid / terephthalic acid and esters of naphthalic acid / naphthalic acid, especially esters of 2-sodium sulfonyl isophthalic acid / 2-sodium sulfonyl isophthalic acid, esters of 4-sodium sulfonyl isophthalic acid / 4-sodium sulfonyl isophthalic acid, esters of 5-sodium sulfonyl isophthalic acid / 5-sodium sulfonyl isophthalic acid, esters of 2-sodium sulfonyl terephthalic acid / 2-sodium sulfonyl terephthalic acid, esters of 2,6-dicarboxynaphthalene-4-sodium sulfonic acid / 2,6-dicarboxynaphthalene-4-sodium sulfonic acid and esters of 2,6-dicarboxynaphthalene-7-sodium sulfonic acid / 2,6-dicarboxynaphthalene-7-sodium sulfonic acid; - Sodium dialkyl sulfosuccinate.

7. The polyesteramide polymer according to claim 6, wherein, The aliphatic / aromatic sulfonated dicarboxylic acid / dicarboxylic acid ester is an aromatic sulfonated dicarboxylic acid / dicarboxylic acid ester, preferably 5-sodium sulfonated isophthalic acid or its ester, especially 5-sodium sulfonated isophthalic acid (SSIA).

8. The polyesteramide polymer according to any one of claims 1 to 7, wherein, The compound [DEDA], containing two ester functional groups and two amide functional groups, is a compound having the general formula (II): (II) in: -R1 is an aryl, alkyl, or cycloalkyl diyl; -R2 and R3 may be the same as or different from each other, and are hydrogen, or straight-chain, branched, or cyclic hydrocarbon groups, which may optionally have one or more heteroatoms inserted and / or be optionally substituted by one or more functional groups; and -R4 and R5 may be the same as or different from each other, and are alkyl groups.

9. The polyesteramide polymer according to claim 8, wherein, The aryl dimethyl group is phenylene or furanyl.

10. The polyesteramide polymer according to claim 8, wherein, The cycloalkyldiyl group is a cyclohexanediyl group.

11. The polyesteramide polymer according to claim 8, wherein, The alkyl dienoyl group is C1-C. 20 Alkyl group.

12. The polyesteramide polymer according to any one of claims 1 to 11, wherein the polyester is prepared by polycondensation of the following monomers (a) to (d): (a) 1,4-Cyclohexanedicarboxylic acid (CHDA); (b) Ethylene glycol (EG); (c) 5-Sodium sulfoisophthalic acid (SSIA); (d) Compounds selected from the group consisting of: DEDA of formula (III) (CY-GLA), DEDA of formula (IV) (FU-GLA), DEDA of formula (V) (TE-GLA), and DEDA of formula (VI) (SU-GLA). (III) (IV) (V) (WE).

13. The polyesteramide polymer according to claim 12, wherein, Monomer (d) is DEDA (FU-GLA) with formula (IV).

14. A polyesteramide polymer comprising the following repeating units: CHDA-EG, SSIA-EG, and DEDA-EG (e.g., FU-GLA-EG, CY-GLA-EG, TE-GLA-EG, and SU-GLA-EG).

15. A method for synthesizing a polyesteramide polymer according to any one of claims 1 to 14, the method comprising a polycondensation step of monomers (a), (b), (c) and (d) in the presence of a catalyst, preferably a hydrolysis-stable catalyst, more preferably a chelate derived from a titanium salt or zirconium salt of ethanolamine, particularly titanium (triethanolamine) isopropoxide (IV).

16. The method according to claim 15, wherein, Monomers (a), (b), (c) and (d) are first mixed and then subjected to a polycondensation reaction by increasing the temperature and / or decreasing the pressure.

17. Use of the polyesteramide polymer according to any one of claims 1 to 14, or the polyesteramide polymer obtained by the method according to claim 15 or 16, as a dispersant for an active ingredient.

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