Diester-diamide compound and polymers comprising a repeating unit derived from the same

Abstract

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

Description

Diester-diamide compound and polymers comprising a repeating unit derived from the sameRELATED APPLICATIONS[1] This application claims priorities of IN provisional application 202311058191 filed on August 30, 2023, and of EP patent application 23203690.5 filed on October 16, 2023, the whole content of each of these applications being incorporated herein by reference for all purposes.FIELD OF THE INVENTION[2] The invention relates to a novel diester-diamide compound and water-soluble biodegradable polyesteramide polymers comprising a repeating unit derived from the same.BACKGROUND OF THE INVENTION[3] Diester-diamide compounds are well known with applications in many fields.[4] Chem. Commun., 2022, 58, 6461-6464 discloses a technology tuning the molecular conformation of the helical building blocks for supramolecular helices, by taking the intramolecular chalcogen bonding. Several helical building blocks produced from diester-diamide compounds such as T-F(AOEt)2 and L,L-F(AOEt)2 were studied to compare their molecular conformation. Macromol. Rapid Commun. 2012, 33, 1535-1541 reports the rational design and synthesis of a family of effective low-molecular-weight gelators(LMWGs) with a modular architecture based on a C2-1 ,4-diamide cyclohexane core. Six gelators(M1-M6) were synthesized. Among these, diester-diamide compounds were synthesized as intermediates of M2, M3 and M6. However, these applications are not related to polymer preparation.[5] CN 101863795 discloses the following diester-diamide compound. However, the phenyl group in the monomer will be more hydrophobic, thereby limiting the water solubility of the resulting polyesteramide polymers.[6] It has been reported that phenyl-group based diester-diamide can be used as a monomer for the preparation of polymers. For example, Journal of Polymer Science: Part A: Polymer Chemistry, Vol. 39, 4283-4293 (2001) teaches a polyesteramide (PEA) derived from diol and phenyl-group based diester-diamide monomer. However, the application of such monomer in water-soluble polymers is very limited due to its hydrophobicity.[7] Journal of Polymer Research Vol.27, No.5, 23 April 2020 reports polyesteramides derived from isosorbide and a -amino acids. However, said polyester- amdes does not have good hydrophilicity-lipophilicity balance (HLB), which affects the water solubility, mechanical and thermal properties.[8] Therefore, an object of the present invention is to provide a novel diester-diamide compound, which is suitable for preparing water-soluble biodegradable polyesteramide polymers mentioned below.[9] In another aspect of the present invention, the present invention relates to a water-soluble biodegradable polyesteramide(PEA) polymer comprising a repeating unit derived from the novel diester-diamide compound.BRIEF OF DESCRIPTION OF DRAWINGS

[0010] Fig.1. A typical1H-NMR of Fll-GLA monomer in DMSO-de at room temperature showing characteristics peaks of different protons;

[0011] Fig.2. A typical13C-NMR of Fll-GLA monomer in CDCb at room temperature showing characteristics peaks of different carbons;

[0012] Fig. 3. Thermogravimetric analysis (TGA) plot of Fll-GLA monomer;

[0013] Fig. 4. Differential scanning calorimetry (DSC) plot of Fll-GLA monomer;

[0014] Fig. 5. Elemental analysis of Fll-GLA monomer;

[0015] Fig. 6. Fll-GLA monomer in distilled water with varying concentration from 20 g / L to 120 g / L;

[0016] Fig. 7. A typical1H-NMR of CY-GLA monomer in DMSO-de at room temperature showing characteristics peaks of different protons;

[0017] Fig. 8. A typical13C-NMR of CY-GLA monomer in DMSO-de at room temperature showing characteristics peaks of different carbons;

[0018] Fig. 9. A typical1H-NMR of Ex. 6 polymer in DMSO-de at room temperature showing characteristics peaks of different protons;

[0019] Fig. 10. A typical13C-NMR of Ex. 6 polymer in DMSO-de at room temperature showing characteristics peaks of different carbons;

[0020] Fig. 11. Thermogravimetric analysis (TGA) plot of Ex. 6 polymer;

[0021] Fig. 12. Differential scanning calorimetry (DSC) of second heating cycle of Ex. 6 polymer.DETAILED DESCRIPTION OF THE INVENTION

[0022] Diester-diamide compound

[0023] As used herein, the diester-diamide compound is a compound comprising two amide functions and two ester functions.

[0024] The diester-diamide compound of the present invention (hereinafter “DEDA”) has the general formula (I):wherein:R1 is a furylene or 1 ,4-cyclohexanediyl;R2 and R3 same or different from each other, are hydrogen, or a straight, branched, cyclic hydrocarbon radical, which is optionally interrupted by one or several heteroatom(s) and / or which is optionally substituted by one or several functional group(s); and with the proviso that when Ri is cyclohexanediyl, at least one of R2 and R3 is hydrogen.

[0025] The Applicant has now found that the DEDA of the present invention can be used as a monomer for the preparation of water-soluble biodegradable polyesteramide polymers. Said DEDA can balance the crystallinity, water-solubility, thermal and mechanical properties, and biodegradability of the resulting polymers.

[0026] The functional group optionally substitued to R2 or R3 can be selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, alkylated amino, carboxyl, ester, cyano, nitro and halogen.

[0027] The optional heteroatom in R2 or Rs can be O, S, N, F, Cl or Br.

[0028] Preferably, R2 and R3, same or different from each other, are hydrogen, or straight or branched hydrocarbon radical, more preferably hydrogen, or a straight orbranched alkyl, in particular a straight or branched C1-C10 alkyl, such as methyl, ethyl, propyl, isopropyl, isobutyl, sec-butyl and tert-butyl.

[0029] In some preferred embodiments, R2 and R3are the same.

[0030] Examples of DEDA are a compound having the formula (l-A) (hereinafter “FU- GLA”):a compound having the formula (l-B) (hereinafter “CY-GLA”):, and a compound having the formula (l-C) (hereinafter “Fll-AA”):wherein R4 is a straight or branched alkyl, in particular a straight or branched C1- C10 alkyl, such as methyl, ethyl, propyl, isopropyl, isobutyl, sec-butyl and tert-butyl.

[0031] It has been found by the Applicant that the DEDA of the present invention may have a solubility of at least 20 g / L, preferably at least 40 g / L, more preferably at least 80 g / L, most preferably at least 100 g / L in distilled water at room temperature.

[0032] Method for preparing the DEDA

[0033] The DEDA of the present invention may be prepared by any conventional methods known to those skilled in the art.

[0034] When R2 and R3 are same, the method may comprise the following steps:

[0035] a) reacting a diacid having the general formula (II) with excessive thionyl chloride (SOCI2) in the presence of a catalyst to prepare a compound having the general formula (III);

[0036] b) reacting the compound having the general formula (III) obtained in step a) with a compound having the general formula (IV) in the presence of a solvent and a base to prepare a compound having the general formula (I’):where Ri and R2 have the same meanings as defined above.

[0037] 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 from 0.01 :1 to 0.10:1 and preferably from 0.03:1 to 0.05:1.

[0038] In step a), the molar ratio of SOCI2 to the diacid is preferably from 4:1 to 20:1 and more preferably from 8:1 to 12:1.

[0039] The reaction temperature of step a) generally depends on the reaction conditions, such as the reactants. Preferably, the reaction temperature is from 30 to 150 °C, more preferably from 60 to 120 °C and most preferably from 80 to 100 °C.

[0040] The reaction time of step a) is preferably from 3 to 6 hrs.

[0041] In step b), the molar ratio of the compound having the general formula (IV) to the compound having the general formula (III) is preferably from 3:1 to 4:1 and more preferably from 1.5:1 to 2.5:1.

[0042] The base used in step b) can be a tertiary amine and preferably triethylamine (EtsN). The molar ratio of the base to the compound having the general formula (III) is preferably from 2:1 to 6:1 and more preferably from 4:1 to 5:1.

[0043] The solvent used in step b) is not particularly limited as long as its presence does not prevent the reaction or interact with any one of the reactants. Said solvent canbe a halogenated solvent. Excellent results are obtained when the reaction is carried out in dichloromethane (DCM).

[0044] The reaction temperature of step b) is preferably from 10 to 50 °C, more preferably room temperature.

[0045] The reaction time of step b) is preferably from 10 to 20 hrs.

[0046] Advantageously, the reaction of steps a) and b) are carried out under an inert atmosphere, such as a nitrogen, an argon or a helium atmosphere.

[0047] Water-soluble biodegradable polyesteramide polymer

[0048] The invention also relates to a water-soluble biodegradable polyesteramide(PEA) polymer comprising a repeating unit derived from the DEDA having the general formula (I), notably a repeating unit having the general formula (V):wherein:Ri is a furylene or 1,4-cyclohexanediyl;R2 and R3 same or different from each other, are hydrogen, or a straight, branched, cyclic hydrocarbon radical, which is optionally interrupted by one or several heteroatom(s) and / or which is optionally substituted by one or several functional group(s); andwith the proviso that when Ri is cyclohexanediyl, at least one of R2 and R3 is hydrogen.

[0049] In some preferred embodiments, R2 and R3are the same.

[0050] Preferably, the water-soluble biodegradable PEA polymer further comprises a repeating unit having the general formula (VI):wherein Rs is an arenediyl, an alkanediyl or a cyclolkanediyl, optionally bearing one or several ion(s).

[0051] By “arenediyl” is meant a bivalent radical obtained by the removal of one hydrogen atom attached to each of two carbon atoms contained in an aromatic ring of an arene, including, but not limited to phenylene, furylene. The arenediyl includes substituted or unsubstituted arenediyls. The arenediyl group can have one, two, three or four substituents independently selected from the group consisting of: alkyl, alkenyl, alkynyl, alkoxy, alkylated amino, carboxyl, ester, cyano, nitro and halogen.

[0052] By “alkanediyl” is meant a bivalent radical obtained by the removal of two hydrogen atoms attached to one or two carbon atom(s) of an alkane, in particular C1-C20 alkanediyl. The alkanediyl includes substituted or unsubstituted alkanediyls.

[0053] By “cycloalkanediyl” is meant a bivalent radical obtained by the removal of two hydrogen atoms attached to one or two carbon atom(s) of a clycoalkane, including, but not limited to cyclohexanediyl. The cycloalkanediyl includes substituted or unsubstituted cycloalkanediyls.

[0054] Said ion(s) can be preferably anion(s).

[0055] Non-limitative examples of ion(s) are sulfate anion(s), sulfonate anion(s), phosphonate anion(s), carboxylate anion(s) and carbonate anion(s). In particular, sulfonate anion(s) give good results.

[0056] Notably, sulfonate anion is derived from a group being -SO3X, which is attached to Rs, wherein X is chosen among halogens (Cl, F, Br, I), -OM+, wherein M+is a cation selected among H+, NH4+, K+, Li+, Na+, or mixtures thereof.

[0057] Advantageously, when Rs is an arenediyl, it bears one or several ion(s).

[0058] In some preferred embodiments, the water-soluble biodegradable PEA polymer comprises at least two different repeating units of general formula (VI). For example, the polymer can comprise a repeating unit in which Rs is an arenediyl and a repeating unit in which Rs is a cycloalkanediyl. The skilled person can adjust the molar ratio of different repeating units based on desired performance.

[0059] The water-soluble biodegradable PEA polymer may further comprise a repeating unit having the general formula (VII):wherein Rs is an alkanediyl or a cycloalkanediyl, which is optionally interrupted by one or several heteroatom (s).

[0060] The optional heteroatom in Rs can be O, S, N and is preferably O.

[0061] The water-soluble biodegradable PEA polymer according to the invention preferably comprises 1-45% by weight of the repeating unit derived from the DEDA having the general formula (I), more preferably 5-30% by weight, most preferably 10-20% by weight, relative to the total weight of repeating units present in the polymer.

[0062] 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%, more preferably at least 5 wt% at room temperature.

[0063] Advantageously, the water-soluble biodegradable PEA polymer of the present invention has a percentage biodegradation of at least 85%, based on OECD 302B Zahn-Wellens test.

[0064] The OECD 302B Zahn-Wellens test measures the removal of dissolved organic carbon (DOC) or chemical oxygen demand (COD) during biodegradation and the percentage biodegradation is calculated as the ratio of DOC removal to original DOC (or COD removal to original COD).

[0065] In some preferred embodiments, the water-soluble biodegradable PEA polymer comprises repeating units derived from monomers (a) to (d):(a) an aliphatic / aromatic unsulfonated dicarboxylic acid / ester;(b) an aliphatic diol;(c) an aliphatic / aromatic sulfonated dicarboxylic acid / ester;(d) a diester-diamide compound (DEDA) having the general formula (I).

[0066] The aliphatic unsulfonated dicarboxylic acid / ester may be linear or cyclic.Preferred linear aliphatic unsulfonated dicarboxylic acids / esters according to the invention are alkyldicarboxylic acids / esters of formula ROOC-(CH2)n-COOR where n = 2-4 and R is H, a Ci to Cs alkyl or phenyl group. Preferred cycloaliphatic unsulfonated dicarboxylic acids / esters according to the invention are based on cycles with 5 or 6 carbon atoms i.e. cyclopentanedicarboxylic acids / alkyl esters or cyclohexanedicarboxylic acids / alkyl esters, in particular 1 ,2- cyclopentanedicarboxylic acid, 1 ,3-cyclopentanedicarboxylic acid, 1 ,3- cyclohexanedicarboxylic acid or 1 ,4-cyclohexanedicarboxylic acid and their corresponding alkyl esters where the alkyl group can vary from methyl to octyl or can be a phenyl group.

[0067] Preferred aromatic unsulfonated dicarboxylic acids / esters are terephthalic acid / alkyl esters and isophthalic acid / alkyl esters where the alkyl group can vary from methyl to octyl or can be a phenyl group.

[0068] The aliphatic / aromatic unsulfonated dicarboxylic acid / ester is preferably an aliphatic one, more preferably a cyclohexane derivative. In particular 1 ,4- cyclohexanedicarboxylic acid (CH DA) gives good results in the frame of the present invention.

[0069] The aliphatic diol used in 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 a polyethylene glycol having an ethylene oxide number ranging from 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.

[0070] Preferably, linear aliphatic diols are used, more preferably alkyl diols, in particular ethylene glycol (EG).

[0071] The aliphatic / aromatic sulfonated 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 a number of aromatic rings, when aromatic dicarboxylic acids or their alkyl diesters are involved, or to the aliphatic chain when aliphatic dicarboxylic acids / alkyl diesters are involved, where the alkyl group can vary from methyl to octyl or can be a phenyl group.

[0072] Aromatic sulfonated dicarboxylic acids / esters monomers that can be used in the frame of the invention are preferably isophthalic acid / esters, terephthalic acid / esters and naphthalenedicarboxylic acids / esters. Preferred ones are 2- sodiosulfoisophthalic acid / ester, 4-sodiosulfoisophthalic acid / ester, 5- sodiosulfoisophthalic acid / ester, 2-sodiosulfoterephthalic acid / ester, 2,6- dicarboxyl naphthalene-4-sodiosulfonic acid / ester and 2,6-dicarboxyl naphthalene-7-sodiosulfonic acid / ester. Aliphatic sulfonated dicarboxylic acids / esters that can be used in the frame of the present invention are dialkyl sodium sulfosuccinates.

[0073] Aromatic sulfonated dicarboxylic acid / ester monomers are preferably used in the frame of the invention, more preferably 5-sodiosulfoisophthalic acid / esters, in particular 5-sodiosulfoisophthalic acid (SSIA).

[0074] A particularly preferred polyesteramide of the invention is prepared by polycondensation of the following monomers (a) to (d):(a) 1 ,4-cyclohexanedicarboxylic acid (CHDA);(b) ethylene glycol (EG);(c) 5-sodiosulfoisophthalic acid (SSIA);(d) FU-GLA.

[0075] A particularly preferred polyesteramide of the invention is prepared by polycondensation of the following monomers (a) to (d):(a) 1 ,4-cyclohexanedicarboxylic acid (CHDA);(b) ethylene glycol (EG);(c) 5-sodiosulfoisophthalic acid (SSIA);(d) CY-GLA.

[0076] A particularly preferred polyesteramide of the invention is prepared by polycondensation of the following monomers (a) to (d):(a) 1 ,4-cyclohexanedicarboxylic acid (CHDA);(b) ethylene glycol (EG);(c) 5-sodiosulfoisophthalic acid (SSIA);(d) FU-AA.

[0077] The present invention also concerns a novel and inventive polyesteramide polymer comprising the following repeat units: CHDA-EG, SSIA-EG and DEDA- EG (i.e. FU-GLA-EG, CY-GLA-EG, FU-AA-EG).

[0078] Advantageously, the ratio of the moles of monomer (b) to the total moles of monomers (a), (c) and (d) in the polymer backbone is about 1 :1 , for instance from 0.8 to 1.2, preferably from 0.9 to 1.1. Thus, the polyesteramide 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 moles of monomers (a), (b) (c) and (d). Particularly, monomer (c) has a mole percentage from 0.01 to 10 mol% and monomer (d) has a mole percentage from 0.01 to 25 mol%, based on the total moles of monomers (a), (b) (c) and (d). The amount of monomers (a) can be adjusted to achieve a total mole percentage of 50 %. Hence, monomer (a) preferably has a mole percentage from 15 to 49.98 mol%.

[0079] It can be understood by the skilled person that excess monomer (b) can be present in the reaction mixture when it is also used as a solvent of solid reactants. Said excess monomer (b) can be added at the beginning of polymerization reaction or during polymerization reaction. In a preferred embodiment, the polymerization can be performed with a mixture in which the ratio of the moles of monomer (b) to the total moles of monomers (a), (c) and (d) is about 1 :1 to 6:1 and more preferably 3:1 to 5:1.

[0080] The weight average molecular weight of the polyesteramide can vary from 5000 to 30000 g / mol.

[0081] Preferred polyesteramides according to the invention comprise at most 15-30 mol% of aromatics (e.g. SSIA and DEDA comprising aromatic ring) in order to promote / facilitate biodegradability.

[0082] The present invention also concerns a process for synthesizing the above described polyesteramide polymer by polycondensation of monomers (a), (b), (c) and (d), preferably in the presence of a catalyst. This catalyst is preferably a hydrolysis-stable catalyst, more preferably chosen from chelates of titanium salts or of zirconium salts derived from ethanol amines, separately and / or mixtures orsolutions thereof. In particular, Titanium(IV) (triethanolaminato)isopropoxide gives good results. This compound is available as a 80wt% solution in isopropanol under the brand name Tyzor® TE.

[0083] The polycondensation according to the invention is preferably initiated on the mixture of all monomers (a) to (d) i.e. monomers (a), (b), (c) and (d) are first mixed and then, reacted by polycondensation, preferably by raising temperature and / or reducing pressure. Alternatively, the polycondensation can be initiated on a mixture of only some of the monomers, the others being introduced in a delayed manner. Still another possibility is to prepare 2 or more prepolymers by polycondensation and then, to proceed to transesterification of the prepolymers.

[0084] In a preferred embodiment, the procedure for the preparation of the polyesteramides according to the invention is as follows. First, all the 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 a nitrogen blanket. The reaction mixture is then preferably maintained at the same temperature for 30 to 240 minutes, preferably for 60 to 180 minutes under agitation. Subsequently, the reaction temperature is preferably raised to 200 °C and gradually a reduced pressure of 50 to 300 mbar, preferably of 100 to 200 mbar is achieved; under this condition, diol, such as ethylene glycol starts distilling 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. As the reaction achieves the desired temperature, the pressure is then preferably further reduced to about 10 mbar to 50 mbar, preferably to about 20 to 40 mbar. The reaction is then preferably maintained for 30 to 240 minutes, preferably for 60 to 180 minutes in this condition after which the polymer can be discharged in hot condition.

[0085] Compared with the DEDAs previously reported for preparing polymers, the DEDA of the present invention shows several advantages, including: i) It can reduce the energy consumption for preparing the resulting polymers; ii) It can provide more hydrophilicity and better flexibility to the resulting polymers; iii) Biobased starting material, especially when Ri is a furylene.EXAMPLES

[0086] Materials2,5-Furandicarboxylic acid (CAS no: 3238-40-2), TCI Chemicals (India); 1 ,4-Cyclohexanedicarboxylic acid (CAS no: 1076-97-7), Sigma-Aldrich; Thionyl chloride (CAS no: 7719-09-7), SD fine-chem;- Anhydrous / V, / V-dimethylformamide (CAS no: 68-12-2), Sigma-Aldrich; Glycine methyl ester hydrochloride (CAS no: 5680-79-5), TCI;- Anhydrous dichloromethane (CAS no: 75-09-2), Sigma-Aldrich; Triethylamine (CAS no: 121-44-8), Sigma-Aldrich;5-Sodiosulfoisophthalic acid (CAS No: 6362-79-4), Sigma-Aldrich; Ethylene glycol (CAS no: 107-21-1), SD fine-chem;Tyzor® TE organic titanate (CAS no: 74665-17-1), Sigma-Aldrich.

[0086] Example 1

[0087] Diacid to diacyl chloride (2,5-furandicarbonyl dichloride)

[0088] A two-neck 250 mL round-bottom flask was fitted with a condenser, magnetic stirrer and oil bath. The required amount of 2,5-furandicarboxylic acid was charged into the reaction vessel and purged with N2 gas two times. Next, freshly distilled SOCI2 (10 equiv.) and a catalytic amount of anhydrous DMF (0.04 equiv.) were introduced into the reactor and the mixture was refluxed at 80 °C for 5 h with constant stirring. The condenser was connected to a washing bottle (minimum two in series), filled with a concentrated sodium hydroxide (NaOH) aqueous solution. After the reaction, the excess of SOCI2 and DMF was 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 at room temperature for 4 h. The product was stored under an inert atmosphere and used for the next step without further purification.

[0089] Diacyl chloride to DEDA monomer (Fll-GLA)

[0090] A two-neck 1 L RB flask was fitted with a condenser, magnetic stirrer and a dropping funnel. The reactor was purged with inert gas two times, solid glycinemethyl ester hydrochloride (2.1 equiv.) 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 dropwise addition of Et3N (5 equiv.) to the reaction mixture. After several minutes, the as-prepared 2,5- furandicarbonyl dichloride (1 equiv.) solution in anhydrous DCM (0.5 mL / mmol of diacyl chloride) was added slowly to the reaction mixture over a period of 45 minutes. Finally, the reaction mixture was stirred overnight at room temperature. The insoluble white precipitate was removed by filtration and the solution was dried under rotary evaporator at 45 °C. The crude mixture was re-dissolved in an excess amount of CHCh and cooled down to -5 °C. After 1 h, the insoluble precipitate was removed again by filtration and the solution was washed with 3% NaHCOs and distilled water. The organic layer was dried over Na2SC>4, concentrated by a rotary evaporator and dropwise added to excess n-hexane (~ 5-6 times) to yield the target product. Finally, the product was dried under vacuum at 60 °C for several hours. The Fll-GLA product was characterized by1H / 13C NMR(Fig. 1 and Fig. 2), LC-MS, TGA(Fig. 3), DSC(Fig. 4) and elemental analysis(Fig. 5). Solubility of Fll-GLA monomer in distilled water was tested, as shown by Fig. 6.FU-GLA

[0091] Example 2

[0092] Diacid to diacyl chloride (1 ,4-cyclohexanedicarbonyl dichloride)

[0093] A two-neck 250 mL round-bottom flask was fitted with a condenser, magnetic stirrer and oil bath. The required amount of 1 ,4-cyclohexanedicarboxylic acid was charged into the reaction vessel and purged with N2 gas two times. Next, freshly distilled SOCI2 (10 equiv.) and a catalytic amount of anhydrous DMF (0.05 equiv.) were introduced into the reactor and the mixture was refluxed at 80 °C for 6 h with constant stirring. The condenser was connected to a washing bottle (minimumtwo in series), filled with a concentrated sodium hydroxide (NaOH) aqueous solution. After the reaction, the excess of SOCh and DMF was 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 at room temperature for 5 h. The product was stored under an inert atmosphere and used for the next step without further purification.

[0094] Diacyl chloride to DEDA monomer (CY-GLA)

[0095] A two-neck 1 L RB flask was fitted with a condenser, magnetic stirrer and a dropping funnel. The reactor was purged with inert gas two times, solid glycine methyl ester hydrochloride (2.1 equiv.) 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 dropwise addition of Et3N (5 equiv.) to the reaction mixture. After several minutes, the as-prepared 1 ,4- cyclohexanedicarbonyl dichloride (1 equiv.) solution in anhydrous DCM (0.5 mL / mmol of diacyl chloride) was added slowly to the reaction mixture over a period of 45 minutes. Finally, the reaction mixture was stirred overnight at room temperature. The insoluble white precipitate was removed by filtration and washed repeatedly by distilled water to remove triethylamine hydrochloride salt generated during the reaction. Finally, the product was dried under vacuum at 60 °C for several hours. The CY-GLA product was characterized by1H / 13C NMR(Fig. 7 and Fig. 8), LC-MS, TGA, and DSC.CY-GLA

[0096] Examples 3 to 4

[0097] Polyesteramides polymers with different DEDA monomers : Synthesis & properties

[0098] General polymerization procedure of Examples 3 to 4The required amount of 1 ,4-cyclohexanedicarboxylic acid (CHDA), 5- sodiosulfoisophthalic acid (SSIA), DEDA, diol, and TyzorOTE (catalyst) were mixed in a glass reactor under atmospheric pressure and N2 gas flow. The polymerization reaction was started by heating the reaction mixture at 160 °C for 1 h under N2 flow, the reaction mixture gradually becomes completely soluble during this period. Next, the reaction temperature raised to 200 °C, N2 flow stopped and vacuum was applied slowly up to 100 mbar. Finally, the temperature was increased in the range of 225-235 °C and gradually vacuum decreased up to 5-10 mbar and the polymerization was continued for another 1-2 h to remove excess of EG and increase the molecular weight (Mw) of PEAs. The final polymer was collected from the glass reactor immediately after the reaction because it is very difficult to collect once cooled down to room temperature.Table 1

[0099] Examples 5 to 8

[0100] Polyesteramides polymers with Fll-GLA monomers : Synthesis & properties

[0101] Following the protocol of Examples 3-4, Examples 5 to 8 with different molar ratios of CHDA, SSIA, Fll-GLA and EG were prepared. The characteristics / properties are listed in Table 2 below.Table 2

[0102] The PEAs of Examples 5 to 8 are a very interesting class of water soluble polymers with various functional moieties like hydrophobic, ionic (anionic nature), hydrophilic and heteroaromatic. It is shown by the testing results in Table 2 that a good balance of crystallinity, water-solubility, thermal and mechanical properties, and biodegradability was obtained.

[0103] Gel permeation chromatography (GPC)

[0104] Molecular weight was measured by gel permeation chromatography (GPC) in a WATERS 515 HPLC pump, Shodex-101 Rl detector and two HFIP gel column with guard column with a flow rate of 0.4 ml / min. PMMA is used as standard, PET is used as reference standard and 0.05 M potassium trifluoro acetate in hexafluoroisopropanol (HFIP) as mobile phase.

[0105] Thermogravimetric analysis (TGA)

[0106] TGA was measured in TA instruments (TGA Q500) from room temperature to maximum 800°C with a heating rate of 20 °C / min. The decomposition temperature (Td) mentioned here is the 10% decomposition of initial sample weight.

[0107] Differential scanning calorimetry (DSC)

[0108] The glass transition temperature (Tg) was measured in TA instruments (DSC Q2000) for two cycles of both cooling and heating in the range of -50 °C to 200 °C with a heating rate of heating rate of 10 °C / min. The reported Tg in the present report have been estimated from the second heating cycle. Tg increased significantly with higher amount of Fll-GLA monomer owing to the incorporation of both amide groups and furan groups. In addition, Tg also increased when SSI A was introduced into the polymer backbone due to increased aromatic groups.Therefore, by careful variation of monomer units the thermal properties as well as mechanical properties of PEAs can be easily tuned.

[0109] Water solubility test results

[0110] In this test, the polymer obtained by Examples 5-8 (with 5-10 mol% of SSIA) were well soluble in distilled water at least in the range of 1-5 wt%.

[0111] Biodegradability test results

[0112] The biodegradability test was done 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.

[0113] In this test, a mixture containing the test substance, mineral nutrients and a relatively large amount of activated sludge in aqueous medium is agitated and aerated at 20-25 °C in the dark or in diffuse light for up to 28 days. Blank controls, containing activated sludge and mineral nutrients but no test substance, are run in parallel. The biodegradation process is monitored by determination of DOC (or COD) in filtered samples taken at daily or other time intervals. The ratio of eliminated DOC (or COD), corrected for the blank, after each time interval, to the initial DOC (or COD) value is expressed as the percentage biodegradation at the sampling time. The percentage biodegradation is plotted against time to give the biodegradation curve.

[0114] The water soluble PEAs containing Fll-GLA were tested and inherently biodegradable in the range of 87-98% in 28 days (Table 2). Interestingly, the biodegradability was not affected by the increased amount of amide containing DEDA monomer in the range of 5-20 mol%.

Claims

1 . A diester-diamide compound has the general formula (I):wherein:Ri is a furylene or 1 ,4-cyclohexanediyl;R2 and R3 same or different from each other, are hydrogen, or a straight, branched, cyclic hydrocarbon radical, which is optionally interrupted by one or several heteroatom(s) and / or which is optionally substituted by one or several functional group(s); and with the proviso that when R1 is cyclohexanediyl, at least one of R2 and R3 is hydrogen.

2. The diester-diamide compound according to claim 1 , wherein R2 and R3, same or different from each other, are hydrogen, or straight or branched hydrocarbon radical.

3. The diester-diamide compound according to claim 2, wherein R2 and R3, same or different from each other, are hydrogen, or a straight or branched alkyl, in particular a straight or branched C1-C10 alkyl, such as methyl, ethyl, propyl, isopropyl, isobutyl, sec-butyl and tert-butyl.

4. The diester-diamide compound according to any one of claims 1 to 3, wherein said diester-diamide compound is a compound having the formula (l-A) (hereinafter “FU-GLA”):a compound having the formula (l-B) (hereinafter “CY-GLA”):, or a compound having the formula (l-C) (hereinafter “Fll-AA”):wherein R4 is a straight or branched alkyl, in particular a straight or branched Ci- C alkyl, such as methyl, ethyl, propyl, isopropyl, isobutyl, sec-butyl and tert-butyl.

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

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

7. The water-soluble biodegradable polyesteramide polymer according to claim6, wherein the repeating unit has the general formula (V):wherein:Ri is a furylene or 1 ,4-cyclohexanediyl;R2 and R3 same or different from each other, are hydrogen, or a straight, branched, cyclic hydrocarbon radical, which is optionally interrupted by one or several heteroatom(s) and / or which is optionally substituted by one or several functional group(s); and with the proviso that when Ri is cyclohexanediyl, 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 comprises 1-45% by weight of the repeating unit derived from the diester-diamide compound according to any one of claims 1 to 5, more preferably 5-30% by weight, most preferably 10-20% by weight, 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 a repeating unit having the general formula (VI):wherein Rs is an arenediyl, an alkanediyl or a cycloalkanediyl, optionally bearing one or several ion(s).

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 sulfonate anion is derived from a group being -SO3X, which is attached to Rs, wherein X is chosen among Cl, F, Br, I, -OM+, wherein M+is a cation selected among H+, NH4+, K+, Li+, Na+, or mixtures thereof.

12. The water-soluble biodegradable polyesteramide polymer according to any one of claims 6 to 11, wherein the polymer further comprises a repeating unit having the general formula (VII):wherein Rs is an alkanediyl or a cycloalkanediyl, which is optionally interrupted by one or several heteroatom (s).

13. The water-soluble biodegradable polyesteramide polymer according to claim 12, wherein the heteroatom in Rs is O, S, N and preferably O.

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%, 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 the polymer has a percentage biodegradation of at least 85%, based on OECD 302B Zahn-Wellens test.

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

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