Diester-diamide compound and polymer comprising repeating unit derived from same

Abstract

The present invention relates to a novel diester-diamide compound and a water-soluble biodegradable polyesteramide polymer comprising repeat units derived from the compound. The DEDA can balance the crystallinity, water solubility, thermal and mechanical properties, and biodegradability of the resulting polymer.

Description

Related applications

[0001] This application claims priority to Indian Provisional Application 202311058191, filed on August 30, 2023, and European Patent Application 23203690.5, 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 relates to a novel diester-diamid compound and a water-soluble, biodegradable polyesteramide polymer comprising repeating units derived from the compound. Background Technology

[0003] Diester-diamid compounds are well known for their applications in many fields.

[0004] Chem. Commun. [Chemical Communications], 2022, 58, 6461-6464 discloses a technique for controlling the molecular conformation of helical structural units for supramolecular helices by utilizing intramolecular chalcogenide bonding. Several helical structural units generated by diester-diamid compounds (such as TF(AOEt)2 and L,LF(AOEt)2) were investigated to compare their molecular conformations. Macromol. Rapid Commun. [Polymer Rapid Communications] 2012, 33, 1535-1541 reports the rational design and synthesis of a class of efficient low molecular weight gelling agents (LMWGs) with a modular architecture based on a C2-1,4-diamidocyclohexane core. Six gelling agents (M1-M6) were synthesized. Among these, diester-diamid compounds were synthesized as intermediates for M2, M3, and M6. However, these applications are not related to polymer preparation.

[0005] CN101863795 discloses the following diester-diamid compounds. However, the phenyl group in the monomer is more hydrophobic, thus limiting the water solubility of the resulting polyesteramide polymer.

[0006]

[0007] It has been reported that phenyl-based diester-diamids can be used as monomers for the preparation of polymers. For example, the Journal of Polymer Science: Part A: Polymer Chemistry, Vol. 39, 4283-4293 (2001) teaches a polyesteramide (PEA) derived from glycols and phenyl-based diester-diamid monomers. However, the application of such monomers in water-soluble polymers is very limited due to their hydrophobicity.

[0008] The Journal of Polymer Research, Volume 27, Issue 5, April 23, 2020, reported polyester-amides derived from isosorbide and α-amino acids. However, these polyester-amides do not exhibit a good hydrophilic-lipophilic balance (HLB), which affects their water solubility, mechanical properties, and thermal properties.

[0009] Therefore, the object of the present invention is to provide a novel diester-diamid compound suitable for preparing the water-soluble, biodegradable polyesteramide polymers mentioned below.

[0010] In another aspect of the invention, the invention relates to a water-soluble, biodegradable polyesteramide (PEA) polymer comprising repeating units derived from the novel diester-diamid compound. Attached Figure Description

[0011] Figure 1 Typical FU-GLA monomers in DMSO-d6 at room temperature 1 H-NMR, which showed characteristic peaks for different protons;

[0012] Figure 2 Typical FU-GLA monomers in CDCl3 at room temperature 13 C-NMR, which showed characteristic peaks for different carbons;

[0013] Figure 3 Thermogravimetric analysis (TGA) plot of FU-GLA monomer;

[0014] Figure 4 Differential scanning calorimetry (DSC) plot of FU-GLA monomer;

[0015] Figure 5 Elemental analysis of FU-GLA monomers;

[0016] Figure 6 The concentration of FU-GLA monomer in distilled water varied from 20 g / L to 120 g / L;

[0017] Figure 7 Typical performance of CY-GLA monomers in DMSO-d6 at room temperature 1 H-NMR, which showed characteristic peaks for different protons;

[0018] Figure 8 Typical performance of CY-GLA monomers in DMSO-d6 at room temperature 13 C-NMR, which showed characteristic peaks for different carbons;

[0019] Figure 9 Example 6: Typical performance of polymers in DMSO-d6 at room temperature. 1 H-NMR, which showed characteristic peaks for different protons;

[0020] Figure 10 Example 6: Typical performance of polymers in DMSO-d6 at room temperature. 13 C-NMR, which showed characteristic peaks for different carbons;

[0021] Figure 11 Example 6: Thermogravimetric analysis (TGA) plot of a polymer;

[0022] Figure 12 Example 6: Differential scanning calorimetry (DSC) for the second heating cycle of a polymer. Detailed Implementation

[0023] Diester-diamid compounds

[0024] As used herein, diester-diamid compounds are compounds containing two amide functional groups and two ester functional groups.

[0025] The diester-diamid compound of the present invention (hereinafter "DEDA") has the general formula (I):

[0026]

[0027] in:

[0028] -R1 is either furanyl or 1,4-cyclohexanediyl;

[0029] -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

[0030] -The premise is that when R1 is cyclohexanediol, at least one of R2 and R3 is hydrogen.

[0031] The applicant has now discovered that the DEDA of the present invention can be used as a monomer for preparing water-soluble, biodegradable polyesteramide polymers. The DEDA can balance the crystallinity, water solubility, thermal and mechanical properties, and biodegradability of the resulting polymer.

[0032] 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.

[0033] The optional heteroatom in R2 or R3 can be O, S, N, F, Cl, or Br.

[0034] 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.

[0035] In some preferred embodiments, R2 and R3 are the same.

[0036] Examples of DEDA are compounds having formula (IA) (hereinafter “FU-GLA”):

[0037]

[0038] Compounds having formula (IB) (hereinafter "CY-GLA"):

[0039]

[0040] Compounds having the formula (IC) (hereinafter "FU-AA"):

[0041] (IC)

[0042] R4 is a straight-chain or branched alkyl group, particularly a straight-chain or branched C1-C group. 10 Alkyl groups, such as methyl, ethyl, propyl, isopropyl, isobutyl, sec-butyl, and tert-butyl.

[0043] The applicant has discovered that the DEDA of the present invention can have a solubility of at least 20 g / L, preferably at least 40 g / L, more preferably at least 80 g / L, and most preferably at least 100 g / L in distilled water at room temperature.

[0044] Methods for preparing DEDA

[0045] The DEDA of the present invention can be prepared by any conventional method known to those skilled in the art.

[0046] When R2 and R3 are the same, the method may include the following steps:

[0047] a) React a diacid having general formula (II) with an excess of thionyl chloride (SOCl2) in the presence of a catalyst to prepare a compound having general formula (III);

[0048]

[0049] b) React the compound of general formula (III) obtained in step a) with the compound of general formula (IV) in the presence of a solvent and a base to prepare the compound of general formula (I'):

[0050]

[0051]

[0052] R1 and R2 have the same meaning as defined above.

[0053] The catalyst used in step a) can be an amide, and preferably anhydrous dimethylformamide (DMF). The molar ratio of the catalyst to the diacid is 0.01:1 to 0.10:1, and preferably 0.03:1 to 0.05:1.

[0054] In step a), the molar ratio of SOCl2 to diacid is preferably 4:1 to 20:1, and more preferably 8:1 to 12:1.

[0055] The reaction temperature in step a) typically depends on the reaction conditions, such as the reactants. Preferably, the reaction temperature is 30°C to 150°C, more preferably 60°C to 120°C, and most preferably 80°C to 100°C.

[0056] The reaction time for step a) is preferably 3 to 6 hours.

[0057] In step b), the molar ratio of the compound having general formula (IV) to the compound having general formula (III) is preferably 3:1 to 4:1, and more preferably 1.5:1 to 2.5:1.

[0058] The base used in step b) can be a tertiary amine, and is preferably triethylamine (Et3N). The molar ratio of the base to the compound having general formula (III) is preferably 2:1 to 6:1, and more preferably 4:1 to 5:1.

[0059] The solvent used in step b) is not particularly limited, as long as its presence does not prevent the reaction or interact with any of the reactants. The solvent may be a halogenated solvent. Excellent results were obtained when the reaction was carried out in dichloromethane (DCM).

[0060] The reaction temperature in step b) is preferably 10°C to 50°C, more preferably room temperature.

[0061] The reaction time for step b) is preferably 10 to 20 hours.

[0062] Advantageously, the reactions in steps a) and b) are carried out under an inert atmosphere (such as nitrogen, argon or helium).

[0063] Water-soluble biodegradable polyesteramide polymer

[0064] The present invention also relates to a water-soluble, biodegradable polyesteramide (PEA) polymer comprising repeating units derived from DEDA having general formula (I), and particularly repeating units having general formula (V):

[0065]

[0066] in:

[0067] -R1 is either furanyl or 1,4-cyclohexanediyl;

[0068] -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

[0069] -The premise is that when R1 is cyclohexanediol, at least one of R2 and R3 is hydrogen.

[0070] In some preferred embodiments, R2 and R3 are the same.

[0071] Preferably, the water-soluble, biodegradable PEA polymer further comprises repeating units having the general formula (VI):

[0072]

[0073] R5 can be an aryl, alkyl, or cycloalkyl group with one or more ions.

[0074] "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.

[0075] "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.

[0076] "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 and unsubstituted cycloalkanediyl groups.

[0077] The one or more ions are preferably one or more anions.

[0078] Non-limiting examples of one or more ions are one or more sulfate anions, one or more sulfonate anions, one or more phosphonate anions, one or more carboxylate anions, and one or more carbonate anions. In particular, one or more sulfonate anions give good results.

[0079] Notably, the sulfonate anion is derived from the -SO3X group attached to R5, where X is selected from halogens (Cl, F, Br, I) and -OM. + M + It is selected from H + NH4 + K + Li + Na + A cation of or a mixture thereof.

[0080] Advantageously, when R5 is an aryl dimethyl group, it carries one or more ions.

[0081] In some preferred embodiments, the water-soluble, biodegradable PEA polymer comprises at least two different repeating units having the general formula (VI). For example, the polymer may comprise a repeating unit wherein R5 is an aryl diel and a repeating unit wherein R5 is a cycloalkane diel. Those skilled in the art can adjust the molar ratio of the different repeating units based on desired performance.

[0082] Water-soluble, biodegradable PEA polymers may further comprise repeating units having the general formula (VII):

[0083]

[0084] R6 can be an alkyldiyl or cycloalkyldiyl group with one or more heteroatoms inserted.

[0085] The optional heteroatom in R6 can be O, S, or N, with O being preferred.

[0086] The water-soluble biodegradable PEA polymer according to the invention preferably comprises 1%-45% by weight, more preferably 5%-30% by weight, and most preferably 10%-20% by weight, of repeating units derived from DEDA having the general formula (I) relative to the total weight of repeating units present in the polymer.

[0087] Advantageously, the water-soluble biodegradable PEA polymer of the present invention has a solubility in distilled water of at least 1 wt%, preferably at least 1.5 wt%, and more preferably at least 5 wt% at room temperature.

[0088] Advantageously, based on the OECD 302B Zahn-Wellens test, the water-soluble biodegradable PEA polymer of the present invention has a biodegradation percentage of at least 85%.

[0089] The OECD 302B Zane-Whelan test measures the removal of dissolved organic carbon (DOC) or chemical oxygen demand (COD) during biodegradation, and the percentage of biodegradation is calculated as the ratio of DOC removal to original DOC (or COD removal to original COD).

[0090] In some preferred embodiments, the water-soluble biodegradable PEA polymer comprises repeating units derived from monomers (a) to (d):

[0091] (a) Aliphatic / aromatic unsulfonated dicarboxylic acids / esters of dicarboxylic acids;

[0092] (b) Aliphatic diols;

[0093] (c) Aliphatic / aromatic sulfonated dicarboxylic acids / esters of dicarboxylic acids;

[0094] (d) Diester-diamid compounds having the general formula (I) (DEDA).

[0095] Aliphatic unsulfonated dicarboxylic acid / dicarboxylic acid esters can be linear or cyclic. A preferred linear aliphatic unsulfonated dicarboxylic acid / dicarboxylic acid ester according to the invention has the formula ROOC-(CH2). n -COOR alkyl dicarboxylic acid / alkyl dicarboxylic acid esters, wherein n = 2-4, and R is H, C1 to C8 alkyl, or phenyl. Preferred alicyclic unsulfonated dicarboxylic acid / dicarboxylic acid esters according to the invention are based on a ring having 5 or 6 carbon atoms, i.e., alkyl esters of cyclopentanedicarboxylic acid / cyclopentanedicarboxylic acid or alkyl esters of cyclohexanedicarboxylic acid / cyclohexanedicarboxylic acid, particularly 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 can vary from methyl to octyl, or can be phenyl.

[0096] Preferred aromatic, unsulfonated dicarboxylic acid / dicarboxylic acid esters are 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.

[0097] The aliphatic / aromatic unsulfonated dicarboxylic acid / dicarboxylic acid esters are preferably aliphatic unsulfonated dicarboxylic acid / dicarboxylic acid esters, more preferably cyclohexane derivatives. In particular, 1,4-cyclohexanedicarboxylic acid (CHDA) has yielded good results within the framework of this invention.

[0098] The aliphatic diol used in this invention can be a straight-chain aliphatic diol selected from the group consisting of alkyl diols such as ethylene glycol or propylene glycol, diethylene glycol, triethylene glycol, or polyethylene glycol with a number of 4 to 75 ethylene oxide atoms. Alternatively, it can be a cyclic saturated diol preferably containing 5 or 6 carbon atoms, i.e., cyclopentanediol or cyclohexanediol, particularly 1,2-cyclopentanediol, 1,3-cyclopentanediol, 1,3-cyclohexanediol, or 1,4-cyclohexanediol.

[0099] Preferably, straight-chain aliphatic diols are used, more preferably alkyl diols, especially ethylene glycol (EG).

[0100] The aliphatic / aromatic sulfonated dicarboxylic acid / dicarboxylic acid ester has at least one sulfonic acid group, preferably in the form of an alkali metal (preferably sodium) sulfonate, and two acid / ester functional groups attached to one or more aromatic rings (when involving aromatic dicarboxylic acids or their alkyl diesters), or two acid / ester functional groups attached to an aliphatic chain (when involving alkyl diesters of aliphatic dicarboxylic acids / aliphatic dicarboxylic acids), wherein the alkyl group can vary from methyl to octyl, or can be phenyl.

[0101] The aromatic sulfonated dicarboxylic acid / dicarboxylic acid ester monomers that can be used in the framework of this invention are preferably esters of isophthalic acid / isophthalic acid, terephthalic acid / terephthalic acid, and naphthalic acid / naphthalic acid. Preferably, they are esters of 2-sodium sulfonyl isophthalic acid / 2-sodium sulfonyl isophthalic acid, 4-sodium sulfonyl isophthalic acid / 4-sodium sulfonyl isophthalic acid, 5-sodium sulfonyl isophthalic acid / 5-sodium sulfonyl isophthalic acid, 2-sodium sulfonyl terephthalic acid / 2-sodium sulfonyl terephthalic acid, 2,6-dicarboxynaphthalene-4-sodium sulfonic acid / 2,6-dicarboxynaphthalene-4-sodium sulfonic acid, and 2,6-dicarboxynaphthalene-7-sodium sulfonic acid / 2,6-dicarboxynaphthalene-7-sodium sulfonic acid. The aliphatic sulfonated dicarboxylic acid / dicarboxylic acid ester that can be used in the framework of this invention is sodium dialkyl sulfosuccinate.

[0102] Within the framework of this invention, aromatic sulfonated dicarboxylic acid / dicarboxylic acid ester monomers are preferably used, more preferably esters of 5-sodium sulfonated isophthalic acid / 5-sodium sulfonated isophthalic acid, especially 5-sodium sulfonated isophthalic acid (SSIA).

[0103] The particularly preferred polyesteramide of the present invention is prepared by polycondensation of the following monomers (a) to (d):

[0104] (a) 1,4-Cyclohexanedicarboxylic acid (CHDA);

[0105] (b) Ethylene glycol (EG);

[0106] (c) 5-Sodium sulfoisophthalic acid (SSIA);

[0107] (d)FU-GLA.

[0108] The particularly preferred polyesteramide of the present invention is prepared by polycondensation of the following monomers (a) to (d):

[0109] (a) 1,4-Cyclohexanedicarboxylic acid (CHDA);

[0110] (b) Ethylene glycol (EG);

[0111] (c) 5-Sodium sulfoisophthalic acid (SSIA);

[0112] (d) CY-GLA.

[0113] The particularly preferred polyesteramide of the present invention is prepared by polycondensation of the following monomers (a) to (d):

[0114] (a) 1,4-Cyclohexanedicarboxylic acid (CHDA);

[0115] (b) Ethylene glycol (EG);

[0116] (c) 5-Sodium sulfoisophthalic acid (SSIA);

[0117] (d)FU-AA.

[0118] The present invention also relates to a novel and inventive polyesteramide polymer comprising the following repeating units: CHDA-EG, SSIA-EG and DEDA-EG (i.e., FU-GLA-EG, CY-GLA-EG, Fu-AA-EG).

[0119] Advantageously, the ratio of the molar number of monomer (b) to the total molar number 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. Therefore, the polyesteramide polymer of the present invention is preferably derived from a reaction mixture in which the total molar percentage of monomers (a), (b), (c), and (d) is 50% based on the total molar number of monomers (a), (b), (c), and (d). Specifically, monomer (c) has a molar percentage of 0.01 to 10 mol% and monomer (d) has a molar percentage of 0.01 to 25 mol%. The amount of monomer (a) can be adjusted to achieve a total molar percentage of 50%. Therefore, monomer (a) preferably has a molar percentage of 15 to 49.98 mol%.

[0120] Those skilled in the art will understand that excess monomer (b) may be present in the reaction mixture when monomer (b) is also used as a solvent for the solid reactants. The excess monomer (b) may be added at the start of the polymerization reaction or during the polymerization reaction. In a preferred embodiment, polymerization can be carried out with a mixture in which the ratio of the molar number of monomer (b) to the total molar number of monomers (a), (c), and (d) is about 1:1 to 6:1, and more preferably 3:1 to 5:1.

[0121] The weight-average molecular weight of polyesteramide can vary from 5,000 to 30,000 g / mol.

[0122] The preferred polyesteramides according to the invention contain up to 15-30 mol% of an aromatic moiety (e.g., SSIA and DEDA containing an aromatic ring) to promote / facilitate biodegradability.

[0123] The present invention also relates to a method for synthesizing the above-mentioned polyesteramide polymer by polycondensation of monomers (a), (b), (c), and (d) (preferably in the presence of a catalyst). The catalyst is preferably a hydrolysis-stabilized catalyst, more preferably selected from chelates of titanium or zirconium salts derived from ethanolamine, alone and / or mixtures or solutions thereof. In particular, titanium (triethanolamine) isopropoxide (IV) yields good results. This compound is available as an 80 wt% solution in isopropanol under the trade name Tyzor® TE.

[0124] The polycondensation according to the invention preferably begins on a mixture of all monomers (a) to (d), i.e., monomers (a), (b), (c), and (d) are first mixed, and then the reaction is carried out by polycondensation (preferably by increasing the temperature and / or decreasing the pressure). Alternatively, polycondensation may begin on a mixture of only some monomers, with the other monomers introduced in a delayed manner. Another possibility is to prepare two or more prepolymers by polycondensation, and then perform transesterification of the prepolymers.

[0125] In a preferred embodiment, the procedure for preparing the polyesteramide according to the invention is as follows. First, all monomers are mixed in a reaction vessel and the mixture is heated under nitrogen protection from about 110°C to 200°C, preferably from 120°C to 180°C. The reaction mixture is then preferably maintained at the same temperature with stirring for 30 to 240 minutes, preferably 60 to 180 minutes. Subsequently, the reaction temperature is preferably increased to 200°C and gradually reduced to a reduced pressure of 50 to 300 mbar, preferably 100 to 200 mbar; under these conditions, the diol (such as ethylene glycol) begins to distill and is preferably collected in a receiver. The reaction temperature is then preferably increased under reduced pressure to between about 210°C and 250°C. When the reaction reaches the desired temperature, the pressure is preferably further reduced to about 10 to 50 mbar, preferably to about 20 to 40 mbar. The reaction is then preferably maintained under these conditions for 30 to 240 minutes, preferably 60 to 180 minutes, after which the polymer can be discharged hot.

[0126] Compared with previously reported DEDAs for polymer preparation, the DEDA of the present invention exhibits several advantages, including:

[0127] i) It can reduce the energy consumption used to prepare the resulting polymer;

[0128] ii) It can provide the resulting polymer with greater hydrophilicity and better flexibility;

[0129] iii) Bio-based starting materials, especially when R1 is furanyl. Example

[0130] Material

[0131] 2,5-Furandicarboxylic acid (CAS No.: 3238-40-2), Tokyo Chemicals (India) Co., Ltd.

[0132] -1,4-Cyclohexanedicarboxylic acid (CAS No.: 1076-97-7), Sigma-Aldrich.

[0133] -Thionyl chloride (CAS No.: 7719-09-7), SD Fine-Chem.

[0134] - Anhydrous N,N-dimethylformamide (CAS No.: 68-12-2), Sigma-Aldrich;

[0135] - Glycine methyl ester hydrochloride (CAS No.: 5680-79-5), Tokyo Chemical Industry Co., Ltd. (TCI);

[0136] - Anhydrous dichloromethane (CAS No.: 75-09-2), Sigma-Aldrich;

[0137] - Triethylamine (CAS No.: 121-44-8), Sigma-Aldrich;

[0138] 5-Sodium-sulfonyl isophthalic acid (CAS No.: 6362-79-4), Sigma-Aldrich;

[0139] - Ethylene glycol (CAS No.: 107-21-1), SD Fine Chemicals Company;

[0140] -Tyzor® TE Organic Titanate (CAS No.: 74665-17-1), Sigma-Aldrich.

[0141] Example 1

[0142] Dicarboxylic acid to diacyl chloride (2,5-furandicarboxylic acid dichloride)

[0143] A two-necked 250 mL round-bottom flask was equipped with a condenser, magnetic stirrer, and oil bath. The required amount of 2,5-furandicarboxylic acid was added to 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 with constant stirring for 5 h. The condenser was connected to a wash bottle (at least two in series) filled with concentrated sodium hydroxide (NaOH) aqueous solution. After the reaction, excess SOCl2 and DMF were removed under vacuum at room temperature and collected in a trap cooled with dry ice and acetone. After removing most of the liquid, the reactants were 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 an inert atmosphere and used for the next step without further purification.

[0144] Diacyl chloride to DEDA monomer (FU-GLA)

[0145] A two-necked 1 L RB flask was equipped with a condenser, magnetic stirrer, and dropping funnel. The reactor was purged twice with an inert gas, and solid glycine methyl ester hydrochloride (2.1 equivalents) and anhydrous dichloromethane (DCM) (3.0 mL / mmol methyl ester) were added to the reactor. The reaction mixture was vigorously stirred at 0°C–5°C, followed by dropwise addition of Et3N (5 equivalents). After a few minutes, a solution of the prepared 2,5-furandicarboxylic acid dichloride (1 equivalent) in anhydrous DCM (0.5 mL / mmol diacyl chloride) was slowly added to the reaction mixture over a 45-minute period. Finally, the reaction mixture was stirred overnight at room temperature. The insoluble white precipitate was removed by filtration, and the solution was dried at 45°C using a rotary evaporator. The crude mixture was redissolved in excess CHCl3 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 with Na₂SO₄, concentrated using a rotary evaporator, and added dropwise to an excess of n-hexane (approximately 5-6 times) to obtain the target product. Finally, the product was dried under vacuum at 60°C for several hours. 1 H / 13 C NMR ( Figure 1 and Figure 2 ), LC-MS, TGA ( Figure 3 ), DSC ( Figure 4 ) and elemental analysis ( Figure 5 The FU-GLA product was characterized. The solubility of the FU-GLA monomer in distilled water was tested, for example, by... Figure 6 As shown.

[0146]

[0147] FU-GLA

[0148] Example 2

[0149] Dicarboxylic acid to diacyl chloride (1,4-cyclohexanedicarboxylic acid dichloride)

[0150] A two-necked 250 mL round-bottom flask was equipped with a condenser, a magnetic stirrer, and an oil bath. The required amount of 1,4-cyclohexanedicarboxylic acid was added to 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 with constant stirring for 6 h. The condenser was connected to a wash bottle (at least two in series) filled with concentrated sodium hydroxide (NaOH) aqueous solution. After the reaction, excess SOCl2 and DMF were removed under vacuum at room temperature and collected in a trap cooled with dry ice and acetone. After removing most of the liquid, the reactants were 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 an inert atmosphere and used for the next step without further purification.

[0151] Diacyl chloride to DEDA monomer (CY-GLA)

[0152] A 1 L RB flask with two necks was fitted with a condenser, magnetic stirrer, and dropping funnel. The reactor was purged twice with an inert gas, and solid glycine methyl ester hydrochloride (2.1 equivalents) and anhydrous dichloromethane (DCM) (3.0 mL / mmol methyl ester) were added to the reactor. The reaction mixture was vigorously stirred at 0°C–5°C, followed by dropwise addition of Et3N (5 equivalents). After a few minutes, a solution of the prepared 1,4-cyclohexanedicarboxyl dichloride (1 equivalent) in anhydrous DCM (0.5 mL / mmol diacyl chloride) was slowly added to the reaction mixture over a 45-minute period. Finally, the reaction mixture was stirred overnight at room temperature. The insoluble white precipitate was removed by filtration and repeatedly washed with distilled water to remove triethylamine hydrochloride formed during the reaction. Finally, the product was dried under vacuum at 60°C for several hours. 1 H / 13 C NMR ( Figure 7 and Figure 8 The CY-GLA products were characterized by LC-MS, TGA, and DSC.

[0153]

[0154] CY-GLA

[0155] Examples 3 to 4

[0156] Polyesteramide polymers with different DEDA monomers: synthesis and properties

[0157] General aggregation program in Examples 3 and 4

[0158] The required amounts of 1,4-cyclohexanedicarboxylic acid (CHDA), 5-sodium sulfoisophthalic acid (SSIA), DEDA, glycol, and Tyzor® TE (catalyst) were mixed in a glass reactor under atmospheric pressure and a nitrogen (N2) flow. The polymerization reaction was initiated by heating the reaction mixture at 160°C for 1 h under a nitrogen (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 a vacuum was slowly applied up to 100 mbar. Finally, the temperature was increased in the range of 225°C–235°C, and the vacuum was gradually decreased up to 5–10 mbar, and the polymerization was continued for another 1–2 h to remove excess EG and increase the molecular weight (Mw) of PEA. The final polymer was collected from the glass reactor immediately after the reaction, as it is very difficult to collect once cooled to room temperature.

[0159] Table 1

[0160]

[0161] Examples 5 to 8

[0162] Polyesteramide polymers with FU-GLA monomers: synthesis and properties

[0163] Following the methods of Examples 3 and 4, Examples 5 to 8 were prepared with CHDA, SSIA, FU-GLA, and EG in different molar ratios. Characteristics / properties are listed in Table 2 below.

[0164]

[0165] Examples 5 to 8 of PEA are a class of very interesting water-soluble polymers with a variety of functional parts, such as hydrophobic, ionic (anionic), hydrophilic, and heteroaromatic functional parts. The test results in Table 2 show that a good balance was achieved in terms of crystallinity, water solubility, thermal and mechanical properties, and biodegradability.

[0166]

[0167] Gel permeation chromatography (GPC)

[0168] Molecular weight was determined by gel permeation chromatography (GPC) in two HFIP gel columns with a Waters 515 HPLC pump, a Shodex-101 RI detector, and guard columns at a flow rate of 0.4 ml / min. PMMA was used as a standard, PET as a reference standard, and 0.05 M potassium trifluoroacetate in hexafluoroisopropanol (HFIP) was used as the mobile phase.

[0169] Thermogravimetric analysis (TGA)

[0170] TGA measurements were performed in a TA instrument (TGA Q500) at a heating rate of 20°C / min from room temperature to a maximum of 800°C. The decomposition temperature (Td) mentioned here is 10% of the initial sample weight at which decomposition occurs.

[0171] Differential scanning calorimetry (DSC)

[0172] The glass transition temperature (Tg) was measured in a TA instrument (DSC Q2000) using two cycles of cooling and heating at a heating rate of 10°C / min within a range of -50°C to 200°C. The Tg reported in this invention report is estimated from the second heating cycle. Due to the simultaneous combination of amide and furan groups, Tg increases significantly with increasing FU-GLA monomer content. Furthermore, when SSIA is introduced into the polymer backbone, Tg also increases due to the increase in aromatic groups. Therefore, the thermal and mechanical properties of PEA can be easily controlled by carefully altering the monomer units.

[0173] Water solubility test results

[0174] In this test, the polymers obtained by Examples 5 to 8 (with 5-10 mol% SSIA) were well soluble in distilled water in the range of at least 1-5 wt%.

[0175] Biodegradability test results

[0176] Biodegradability testing was conducted according to the following: OECD (1992), Test No. 302B: Inherent Biodegradability: Zahn-Wellens / EVPA Test, OECD Guidelines for the Testing of Chemicals, Section 3, OECD Publishing, Paris.

[0177] In this test, a mixture of the test substance, mineral nutrients, and a relatively large amount of activated sludge in an aqueous medium was stirred and aerated for up to 28 days at 20°C–25°C in the dark or under diffused light. A blank control containing activated sludge and mineral nutrients but without the test substance was run in parallel. The biodegradation process was monitored by measuring the DOC (or COD) in filtered samples collected daily or at other time intervals. After each time interval, the ratio of eliminated DOC (or COD) to the initial DOC (or COD) value after blank correction was expressed as the percentage of biodegradation at sampling. The percentage of biodegradation was plotted against time to provide a biodegradation curve.

[0178] Water-soluble PEA containing FU-GLA was tested and was inherently biodegradable within 87%–98% of the range over 28 days (Table 2). Interestingly, biodegradability was not affected by increasing amounts of amide-containing DEDA monomers in the range of 5–20 mol%.

Claims

1. A diester-diamid compound having the general formula (I): in: -R1 is either furanyl or 1,4-cyclohexanediyl; -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 -The premise is that when R1 is cyclohexanediol, at least one of R2 and R3 is hydrogen.

2. The diester-diamid compound according to claim 1, wherein, R2 and R3 may be the same or different from each other, and are hydrogen, or straight-chain or branched hydrocarbon groups.

3. The diester-diamid compound according to claim 2, wherein, R2 and R3 may be the same as or different from each other, and are 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.

4. The diester-diamid compound according to any one of claims 1 to 3, wherein, The diester-diamid compound is a compound having formula (IA) (hereinafter "FU-GLA"): Compounds having formula (IB) (hereinafter "CY-GLA"): Compounds having the formula (IC) (hereinafter "FU-AA"): (I-C) R4 is a straight-chain or branched alkyl group, particularly a straight-chain or branched C1-C group. 10 Alkyl groups, such as methyl, ethyl, propyl, isopropyl, isobutyl, sec-butyl, and tert-butyl.

5. The diester-diamid compound according to any one of claims 1 to 4, wherein, The diester-diamid compound has a solubility of at least 20 g / L, preferably at least 40 g / L, more preferably at least 80 g / L, and most preferably at least 100 g / L in distilled water at room temperature.

6. A water-soluble, biodegradable polyesteramide polymer comprising repeating units derived from the diester-diamid compound according to any one of claims 1 to 5.

7. The water-soluble, biodegradable polyesteramide polymer according to claim 6, wherein, The repeating unit has the general formula (V): in: -R1 is either furanyl or 1,4-cyclohexanediyl; -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 -The premise is that when R1 is cyclohexanediol, at least one of R2 and R3 is hydrogen.

8. The water-soluble, biodegradable polyesteramide polymer according to claim 6 or 7, wherein, The polymer contains 1%-45% by weight, more preferably 5%-30% by weight, and most preferably 10%-20% by weight, of repeating units derived from the diester-diamid compound according to any one of claims 1 to 5, relative to the total weight of repeating units present in the polymer.

9. The water-soluble, biodegradable polyesteramide polymer according to any one of claims 6 to 8, wherein, The polymer further comprises repeating units having the general formula (VI): R5 can be an aryl, alkyl, or cycloalkyl group with one or more ions.

10. The water-soluble, biodegradable polyesteramide polymer according to claim 9, wherein, The ion is selected from the group consisting of sulfate anion, sulfonate anion, phosphonate anion, carboxylate anion and carbonate anion, and preferably sulfonate anion.

11. The water-soluble, biodegradable polyesteramide polymer according to claim 10, wherein, The sulfonate anion is derived from the -SO3X group attached to R5, where X is selected from Cl, F, Br, I, and -OM. + M + It is selected from H + NH4 + K + Li + Na + A cation of or a mixture thereof.

12. The water-soluble, biodegradable polyesteramide polymer according to any one of claims 6 to 11, wherein, The polymer further comprises repeating units having the general formula (VII): R6 can be an alkyldiyl or cycloalkyldiyl group with one or more heteroatoms inserted.

13. The water-soluble, biodegradable polyesteramide polymer according to claim 12, wherein, The heteroatom in R6 is O, S, or N, with O being preferred.

14. The water-soluble, biodegradable polyesteramide polymer according to any one of claims 6 to 13, wherein, The polymer has a solubility in distilled water of at least 1 wt%, preferably at least 1.5 wt%, and more preferably at least 5 wt% at room temperature.

15. The water-soluble, biodegradable polyesteramide polymer according to any one of claims 6 to 14, wherein, Based on the OECD 302B Zane-Whelan test, the polymer has a biodegradability percentage of at least 85%.

16. A polyesteramide polymer comprising the following repeating units: CHDA-EG, SSIA-EG and DEDA-EG (i.e., FU-GLA-EG, CY-GLA-EG, Fu-AA-EG).

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