A COMPOUND, A REACTION PRODUCT OF SAID COMPOUND AND PRODUCTION METHODS THEREOF
20210053953 ยท 2021-02-25
Inventors
Cpc classification
C09D175/12
CHEMISTRY; METALLURGY
C08F283/00
CHEMISTRY; METALLURGY
International classification
C08F283/00
CHEMISTRY; METALLURGY
Abstract
There is provided a compound represented by general formula (lb), wherein ring A is a carbocyclic or heterocyclic ring, a reaction product of the reaction between one or more said compounds and one or more amine containing compounds. Also provided is related production methods thereof.
##STR00001##
Claims
1. A compound represented by general formula (Ib): ##STR00061## wherein ring A is an optionally substituted 5-membered or 6-membered hydrocarbon cyclic ring, or an optionally substituted 5-membered or 6-membered heterocyclic ring having up to three heteroatoms independently selected from the group consisting of O, N, S and NH; Y.sup.1 and Y.sup.2 are each independently selected from the group consisting of: a single bond, ZOZ, ZNR.sup.bZ, ZOC(O)Z, ZC(O)OZ, ZNR.sup.bC(O)Z, ZC(O)NR.sup.bZ, ZNR.sup.bC(O)OZ, ZOC(O)NR.sup.bZ; where each Z is independently selected from the group consisting of a single bond, optionally substituted saturated aliphatic chain and optionally substituted unsaturated aliphatic chain; where R.sup.b is H or C.sub.1-C.sub.6 alkyl, and with the proviso that when ring A is 1,4-phenylene, Y.sup.1 is not (CH.sub.2)OC(O) and Y.sup.2 is not C(O)O(CH.sub.2).
2. The compound according to claim 1, wherein ring A is selected from the group consisting of benzene, furan, thiophene, pyrrole, oxazole, isoxazole, isothiazole, tetrahydrofuran, tetrahydrothiophene, pyrrolidine, pyridine, pyrone, pyridazine, pyrimidine, pyrazine, triazine, piperidine and piperazine.
3. The compound according to claim 1, wherein ring A is selected from any one of the general formulae (II) to (V): ##STR00062## wherein R.sup.3a, R.sup.3b and R.sup.3c are each independently selected from the group consisting of a hydrogen, hydroxy, halogen, cyano, amino, nitro, carboxyl, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, cycloalkyl, cycloalkenyl, alkylcarbonyl and alkoxycarbonyl.
4. The compound according to claim 1, wherein Y.sup.1 is selected from the group consisting of ZOZ and ZOC(O)Z; Y.sup.2 is selected from the group consisting of ZOZ and ZC(O)OZ; each Z is independently selected from the group consisting of a single bond and C.sub.1-C.sub.6 alkyl.
5. The compound according to claim 1 selected from the following: ##STR00063## bis((2-oxo-1,3-dioxolan-4-yl)methyl)furan-2,5-dicarboxylate (FBC-1); ##STR00064## 4,4-(((furan-2,5-diylbis(methylene))bis(oxy))bis(methylene))bis(1,3-dioxolan-2-one) (FBC-2); ##STR00065## bis((2-oxo-1,3-dioxolan-4-yl)methyl)pyridine-2,5-dicarboxylate (PBC); ##STR00066## bis((2-oxo-1,3-dioxolan-4-yl)methyl)pyridine-2,6-dicarboxylate (PBC-2); and ##STR00067## 4,4-(((tetrahydrofuran-3,4-diyl)bis(oxy))bis(methylene))bis(1,3-dioxolan-2-one) (HFBC).
6. A method of preparing the compound according to claim 1, the method comprising: converting a precursor compound represented by general formula (VI) to the compound of claim 1 through one or more chemical reactions: ##STR00068## wherein ring A is an optionally substituted 5-membered or 6-membered hydrocarbon cyclic ring, or an optionally substituted 5-membered or 6-membered heterocyclic ring having up to three heteroatoms independently selected from the group consisting of O, N, S and NH; R.sup.4 and R.sup.5 are each independently selected from the group consisting of OH, C(O)H, C(O)OH, NR.sup.cR.sup.d, C(O)NR.sup.cR.sup.d, (C.sub.1-C.sub.6 alkyl)-OH, (C.sub.1-C.sub.6 alkyl)-C(O)H, (C.sub.1-C.sub.6 alkyl)-C(O)OH, (C.sub.1-C.sub.6 alkyl)-NR.sup.cR.sup.d and (C.sub.1-C.sub.6 alkyl)-C(O)NR.sup.cR.sup.d, where R.sup.c and R.sup.d are independently selected from the group consisting of H or C.sub.1-C.sub.6 alkyl, wherein at least one of the one or more chemical reactions is carried out in the presence of a halogenated compound.
7. The method according to claim 6, wherein ring A is selected from the group consisting of disubstituted benzene, disubstituted furan, disubstituted thiophene, disubstituted pyrrole, disubstituted oxazole, disubstituted isoxazole, disubstituted isothiazole, disubstituted tetrahydrofuran, disubstituted tetrahydrothiophene, disubstituted pyrrolidine, disubstituted pyridine, disubstituted pyrone, disubstituted pyridazine, disubstituted pyrimidine, disubstituted pyrazine, disubstituted triazine, disubstituted piperidine and disubstituted piperazine.
8. The method according to claim 6, wherein the precursor compound is selected from the group consisting of 5-hydroxymethylfurfural (HMF), furan-2,5-diyldimethanol (FDM), furan-2,5-dicarboxylic acid (FDCA), furan-2,5-diyldimethanamine (FBA), pyridine-2,5-dicarboxylic acid, pyridine-2,6-dicarboxylic acid and 1,4-anhydroerythritol.
9. A reaction product of the reaction between one or more compounds according to claim 1 and one or more amine containing compounds, the reaction product having hydroxyl groups and urethane/carbamate linkages.
10. The reaction product according to claim 9, wherein the reaction product is a polymer having a repeating unit represented by general formula (VIIb) or a derivative thereof: ##STR00069## wherein ring A is an optionally substituted 5-membered or 6-membered hydrocarbon cyclic ring, or an optionally substituted 5-membered or 6-membered heterocyclic ring having up to three heteroatoms independently selected from the group consisting of O, N, S and NH; Y.sup.1 and Y.sup.2 are each independently selected from the group consisting of: a single bond, ZOZ, ZNR.sup.bZ, ZOC(O)Z, ZC(O)OZ, ZNR.sup.bC(O)Z, ZC(O)NR.sup.bZ, ZNR.sup.bC(O)OZ, ZOC(O)NR.sup.bZ; where each Z is independently selected from the group consisting of a single bond, optionally substituted saturated aliphatic chain and optionally substituted unsaturated aliphatic chain; where R.sup.b is H or C.sub.1-C.sub.6 alkyl; R.sup.6 is selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted polyether, optionally substituted 5-membered or 6-membered hydrocarbon cyclic ring and an optionally substituted 5-membered or 6-membered heterocyclic ring having up to three heteroatoms independently selected from the group consisting of O, and S; X.sup.3 and X.sup.4 are each independently selected from the group consisting of a single bond and (C.sub.1-C.sub.6 alkyl); and with the proviso that when ring A is 1,4-phenylene, Y.sup.1 is not (CH.sub.2)OC(O) and Y.sup.2 is not C(O)O(CH.sub.2).
11. The reaction product according to claim 9, wherein ring A is selected from the group consisting of benzene, furan, thiophene, pyrrole, oxazole, isoxazole, isothiazole, tetrahydrofuran, tetrahydrothiophene, pyrrolidine, pyridine, pyrone, pyridazine, pyrimidine, pyrazine, triazine, piperidine and piperazine.
12. The reaction product according to claim 9, wherein ring A is selected from any one of the general formulae (II) to (V): ##STR00070## wherein R.sup.3a, R.sup.3b and R.sup.3c are each independently selected from the group consisting of a hydrogen, hydroxy, halogen, cyano, amino, nitro, carboxyl, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, cycloalkyl, cycloalkenyl, alkylcarbonyl and alkoxycarbonyl.
13. The reaction product according to claim 10, wherein Y.sup.1 is selected from the group consisting of ZOZ and ZOC(O)Z; Y.sup.2 is selected from the group consisting of ZOZ and ZC(O)OZ; each Z is independently selected from the group consisting of a single bond and C.sub.1-C.sub.6 alkyl.
14. The reaction product according to claim 9 selected from the following: ##STR00071## ##STR00072## ##STR00073## ##STR00074## or a derivative thereof.
15. The reaction product according to claim 9, wherein the product has one or more of the following properties: number average molecular weight (Mn) in the range of 2,000 g/mol to 50,000 g/mol, peak molecular weight (Mp) in the range of 1,500 g/mol to 60,000 g/mol and the polydispersity index (PDI) is in the range of 1.0 to 5.0, wherein the number average molecular weight, peak molecular weight and polydispersity index are determined by gel permeation chromatography using polymethyl methacrylate (PMMA) calibration.
16. (canceled)
17. (canceled)
18. (canceled)
19. (canceled)
20. (canceled)
21. (canceled)
22. (canceled)
23. The reaction product according to claim 9, wherein the reaction product is a functionalised or grafted product having one or more of the following properties: solubility or dispersibility in water, solubility or dispersibility in oil, photo or thermo or redox or pH response and crosslinking ability under air, photo, thermal, redox or ionic conditions.
24. The reaction product according to claim 23, wherein the reaction product is a functionalised product obtained by reacting one or more compounds according to claim 1 with one or more amine containing compounds and further functionalising one or more hydroxyl groups present in the reaction product.
25. The reaction product according to claim 23, wherein the reaction product is a grafted product obtained by reacting one or more compounds according to claim 1 with one or more amine containing compounds and further grafting a polymer to one or more hydroxyl groups present in the reaction product.
26. The reaction product according to claim 23, wherein the reaction product is a grafted product obtained by reacting one or more compounds according to claim 1 with one or more amine containing compounds and further grafting one or more molecular entities or polymers to one or more furan rings present in the reaction product.
27. The reaction product according to claim 9, wherein the amine containing compound comprises at least two amine functional groups, optionally wherein the amine containing compound is selected from the group consisting of furan-2,5-diyldimethanamine (FBA), xylene diamine (XDA), diaminopentane (DAP), hexamethylenediamine (HDA), ethylenediamine, diaminopropane, diaminobutane, ether diamine, polyether diamine, dimer diamine, lysine, isophorone diamine and phenylenediamine.
Description
BRIEF DESCRIPTION OF FIGURES
[0165]
[0166]
[0167]
[0168]
[0169]
[0170]
[0171]
[0172]
[0173]
EXAMPLES
[0174] Example embodiments of the disclosure will be better understood and readily apparent to one of ordinary skill in the art from the following examples, tables and if applicable, in conjunction with the figures.
[0175] The examples describe a method of preparing a compound and a method of preparing a reaction product of said compound from a bio-based source in an environmentally benign process in accordance with various embodiments of the present disclosure. Broadly, the general concept of methods disclosed herein may be illustrated in
[0176] Referring to
[0177] Referring now to
[0178] Turning to
[0179] At step 302, one or more compounds in the form of a first monomer type represented by general formula (Ia) and/or (Ib) are provided. At step 304, one or more amine containing compounds in the form of a second monomer type are provided. At step 306, the first and second monomer types are reacted to obtain a polymer represented by general formula (VIIa) and/or (VIIb).
[0180] In addition, the following examples further show that embodiments of the presently disclosed method provide a green and sustainable strategy to produce cyclic biscarbonates and polyhydroxyurethanes as use of toxic isocyanates and phosgene may be avoided.
[0181] As will be shown in the following examples, embodiments of the presently disclosed method synthesize new aliphatic and aromatic cyclic biscarbonates and new polyhydroxyurethanes that are capable of addressing several problems of conventional methods used in the art. The polyhydroxyurethanes disclosed herein are innocuous biocompatible polymers, making them attractive as greener, safer, bio-renewable and sustainable materials for a wide array of applications. It should be appreciated that the examples provided below are meant to be merely illustrative and not in any way meant to be exhaustive or restrictive.
[0182] Bio-Based Cyclic Biscarbonate Monomers
[0183] Several biscarbonate monomers have been developed from bio-based platform chemicals such as 5-hydroxymethylfurfural (HMF), 1,4-anhydroerythritol, pyridine dicarboxylic acid and glycerol. Renewable C-1 feedstock such as CO.sub.2 was also utilized towards creating cyclic carbonate structures. The synthesis protocols for the monomers and the polyhydroxy urethane polymers are summarized in Schemes 2.1, 2.2 and 2.3, and explained below.
##STR00038##
##STR00039##
##STR00040##
[0184] Furan Based Cyclic Biscarbonate Monomers
[0185] The initial synthetic focus was based on the bio-feedstock 5-hydroxymethylfurfural (HMF), which is manufactured by the acid-catalyzed dehydration of hexoses. Recent commercialization of a 20 tons/year scale by AVA Biochem in Muttenz, Switzerland adds to its feedstock security. HMF derived bis-carboxylic acid (FDCA) and bis-diol (FDM) can be good linkers for the synthesis of bis-cyclic carbonate monomers. FDCA is an oxidation product of HMF. Companies such as Aventium (40 tons/y pilot scale), Synbias, Carbone Scientific Tokyo Chemical Industry, V & V Pharma Industries, Chemsky and Good Scents Company are involved in the pilot scale production of FDCA. FDM is a reduction product of HMF and could be available commercially in future. The Bis-carbonate monomers (Scheme 3) can be conveniently synthesized from HMF derivatives using simple organic transformations through ester, ether, amine, amide, or carbamate linkages.
[0186] Furan based cyclic biscarbonate with ester linkage can be synthesized from FDCA or its acid chloride or esters with glycerol carbonate via by standard esterification or transesterification protocols e.g. catalytic esterification/transesterification or by using coupling agents. Furan containing cyclic carbonates with ether linkages can be synthesized from corresponding furan containing diols via alkylations using a carbonate containing halide or pseudo halide or epoxide containing halide or pseudo halide followed by CO.sub.2 insertion.
##STR00041##
Example 1
Synthesis of Furan Based Cyclic Biscarbonate with Ester Linkage
[0187] Furan based cyclic biscarbonate with ester linkage was synthesized from FDCA by a one pot esterification with glycerol carbonate as shown in Scheme 4.
##STR00042##
[0188] To a round bottom flask connected with condenser, FDCA (40 mmol, 6.24 g), SOCl.sub.2 (96 mmol, 7 mL) and 5 mL of dimethylformamide (DMF) were added and the reaction was carried out at 90 C. under argon for 4 h. The reaction mixture was then cooled down to room temperature. Et.sub.3N (125 mmol, 20 mL) and glycerol carbonate (100 mmol, 11.8 g in 25 mL of dry THF) were added slowly and the mixture was further heated to 90 C. overnight. After the reaction, the excess amount of Et.sub.3N, SOCl.sub.2 and DMF were removed under high vacuum. The product was isolated as a white solid, filtered and washed with water (100 mL, 2 times) and with Et.sub.2O (100 mL, 2 times) to give 8.24 g (23.13 mmol) of pure bis((2-oxo-1,3-dioxolan-4-yl)methyl)furan-2,5-dicarboxylate (58%) which was characterized by .sup.1H, .sup.13C-NMR and HRMS. .sup.1H-NMR (DMSO, 400 MHz): 7.42 (s, 2H), 5.16 (m, 2H), 4.6 (m, 6H), 4.4 (dd, J=8.6, 6.1 Hz, 2H). .sup.13C NMR (DMSO, 100 MHz): =156.7, 154.6, 145.8, 119.6, 74.1, 67.0, 64.5. HRMS (ESI) (M+H).sup.+ m/z Calcd. For C.sub.14H.sub.12O.sub.11: 357.0452. Found: 357.0459.
Example 2
Synthesis of Furan Based Cyclic Biscarbonate with Ether Linkage
[0189] The novel cyclic biscarbonate 4,4-(((furan-2,5-diylbis(methylene))-bis(oxy))bis(methylene)) bis(1,3-dioxolan-2-one), FBC-2, was synthesized by using a two-step protocol in multi gram scale starting from FDM as shown in Scheme 5.
##STR00043##
[0190] In the first step, a solution of furandimethanol (FDM) (20 mmol, 2.56 g), epichlorohydrin (200 mmol, 18.5 g) and tetrabutylammonium bromide (TBAB) (20 mol %, 2.57 g) in THF (30 mL) was added into aqueous NaOH (20 g in 20 mL). This mixture was heated and stirred at 70 C. for 24 h. After the reaction, the reaction mixture was diluted with 50 mL of water and the product was extracted into EtOAc (100 mL, 3 times) and the combined organic layers were dried over MgSO.sub.4. After evaporation of the solvent and column chromatography of the crude reaction mixture, the diepoxy product 2,5-bis((oxiran-2-ylmethoxy)-methyl)furan was isolated in 4.32 g (18 mmol), 89% (yellow oil) and characterized by NMR and HRMS as follows. .sup.1H-NMR (CDCl.sub.3, 400 MHz): 6.27 (s, 2H), 4.48 (q, J=8.3 Hz, 4H), 3.74 (dd, J=11.5, 3.1 Hz, 2H), 3.42 (dd, J=11.5, 5.8 Hz, 2H), 3.13 (m, 2H), 2.76 (dd, J=5.1, 4.2 Hz, 2H), 2.58 (dd, J=5.0, 2.7 Hz, 2H). .sup.13C NMR (CDCl.sub.3, 100 MHz): =151.9, 110.3, 70.8, 65.3, 50.8, 44.3. HRMS (ESI) (M+H).sup.+ m/z Calcd. For C.sub.12H.sub.16O.sub.5: 258.1336. Found: 258.1344.
[0191] In the second step, the diepoxy product 2,5-bis((oxiran-2-ylmethoxy)-methyl)furan (18 mmol, 4.32 g), tetrabutyl ammonium iodide (TBAI) (20 mol %, 3.6 mmol) and pyridinedimethanol (20 mol %, 3.6 mmol) were dissolved in 12 mL of dry THF, transferred into a Parr reactor and pressurized with CO.sub.2 up to 150 psig after purging with N.sub.2 followed by CO.sub.2. The reaction was carried out under stirring at 105 C. for 24 h. After the reaction, the reactor was cooled to room temperature and depressurized. The reaction mixture was collected, the solvent evaporated and the product was purified by column chromatography. The bicarbonate product 4,4-(((furan-2,5diylbis(methylene))bis(oxy))-bis(methylene))bis(1,3-dioxolan-2-one) was isolated as a white solid (5.1 g, 15.53 mmol, 86% yield) and characterized by .sup.1H, .sup.13C-NMR and HRMS as follows. .sup.1H-NMR (CDCl.sub.3, 400 MHz): 6.29 (s, 2H), 4.81 (m, 2H), 4.48 (m, 6H), 4.33 (dd, J=8.4, 6.0 Hz, 2H), 3.72 (ddd, J=11.1, 3.6, 2.0 Hz, 2H), 3.62 (dd, J=11.1, 3.8 Hz, 2H). .sup.13C NMR (CDCl.sub.3, 100 MHz): =155.1, 151.6, 110.8, 75.2, 68.8, 66.3, 65.4. HR-MS (ESI) (M+Na).sup.+ m/z Calcd. for C.sub.14H.sub.16O.sub.9Na: 351.0687. Found: 351.0695.
Example 3
Synthesis of Tetrahydrofuran Based Bis-Cyclic-Carbonate with Ether Linkage
[0192] Bioderived aliphatic cyclic diols such as 1,4-anhydroerythritol can be another class of linkers to form aliphatic cyclic biscarbonates with tetrahydrofuran backbone. An aliphatic bio-based cyclic biscarbonate 4,4-(((tetrahydrofuran-3,4-diyl)bis(oxy))bis(methylene))bis(1,3-dioxolan-2one) was synthesized from 1,4-anhydroerythritol, which was derived from the bio-feedstock erythritol. The synthetic protocol for converting 1.4-anhydroerythritol to 4,4-(((tetrahydrofuran3,4-diyl)bis(oxy))bis(methylene))-bis(1,3-dioxolan-2-one) is shown in Scheme 6.
##STR00044##
[0193] 1,4-anhydroerithritol (20 mmol, 2.08 g) was added into a mixture of KOH/THF (100 mmol (5.6 g)/40 mL). Allylbromide (60 mmol, 7.26 g) was added slowly into the mixture. This mixture was heated and stirred at 80 C. (under refluxing) for 18 h. After reaction, the crude reaction mixture was diluted with water (50 mL) and extracted with EtOAc (100 mL, 3 times). The combined organic layers were then dried using MgSO.sub.4, solvent evaporated and the product 3,4-bis(allyloxy)tetrahydrofuran was isolated by column chromatography in 3.53 g, 19.2 mmol (96%) as an yellow oil and characterized by .sup.1H-NMR, .sup.13C-NMR and HRMS. .sup.1H-NMR (CDCl.sub.3, 400 MHz): 6.04-5.79 (m, 2H), 5.37-5.11 (m, 4H), 4.09 (m, 4H), 4.00 (m, 2H), 3.97-3.89 (m, 2H), 3.80 (m, 2H). .sup.13C NMR (CDCl.sub.3, 100 MHz): =134.8, 117.4, 77.7, 71.4, 70.5. HR-MS (ESI) (M+H).sup.+ m/z Calcd. for C.sub.10H.sub.17O.sub.3: 185.1172. Found: 185.1172.
[0194] In the second step, a solution of 3,4-bis(allyloxy)tetrahydrofuran (10 mol, 1.84 g) in dichloromethane (30 mL) was cooled down to 0 C. followed by the addition of m-chloroperoxybenzoic acid (30 mmol, 5.2 g) under stirring. The reaction mixture was allowed to stir and the temperature was slowly brought to room temperature (22 C.) during 6 h. Another portion of m-chloroperoxybenzoic acid (30 mmol) was added into the reaction mixture and the reaction mixture refluxed overnight. The reaction was cooled down to room temperature, 50 mL of water was added and the crude mixture was extracted with EtOAc (100 mL, 3 times). The combined organic layers were dried over MgSO.sub.4, solvent evaporated and the product 3,4-bis(oxiran-2-ylmethoxy)tetrahydrofuran was isolated as a diastereomeric mixture by column chromatography to yield 0.841 g, 3.9 mmol (39%) of product as a colourless oil and was characterized by .sup.1H NMR, .sup.13C-NMR and HRMS. .sup.1H-NMR (CDCl.sub.3, 400 MHz): 4.09-3.97 (m, 2H), 3.94-3.68 (m, 6H), 3.43 (ddd, J=28.0, 11.8, 5.9 Hz, 2H), 3.11 (ddq, J=5.5, 4.0, 2.7 Hz, 2H), 2.73 (m, 2H), 2.61-2.48 (m, 2H). .sup.13C NMR (CDCl.sub.3, 100 MHz): =78.9-78.7, 71.3-71.0, 70.5-70.0, 50.9-50.7, 44.1-44.0. HR-MS (ESI) (M+NH.sub.4).sup.+ m/z Calcd. for C.sub.10H.sub.20NO.sub.5: 234.1336 Found: 234.1343.
[0195] In the third step, 3,4-bis(oxiran-2-ylmethoxy)tetrahydrofuran (1.5 mmol, 324 mg), tetrabutyl ammonium iodide (20 mol %, 110 mg) and pyridine-2,6-diyldimethanol (20 mol %, 42 mg) were dissolved in 12 mL dry THF in a Parr reactor and pressurized with CO.sub.2 (up to 150 psi) after purging with N.sub.2 followed by CO.sub.2. This mixture was heated at 105 C. under stirring for 24 h. After reaction, the Parr reactor was cooled down to room temperature and depressurized. The reaction mixture was collected, the solvent evaporated and the product 4,4-(((tetrahydrofuran-3,4-diyl)bis(oxy))bis(methylene))-bis(1,3-dioxolan-2-one) was isolated as a diastereomeric mixture by column chromatography in 0.187 g, (0.615 mmol, 41% yield) as an yellow oil and characterized by .sup.1H, .sup.13C-NMRs and MS. .sup.1H-NMR (CDCl.sub.3, 400 MHz): 4.84 (m, 2H), 4.52 (m, 2H), 4.40 (m, 2H), 4.09 (m, 2H), 3.95 (m, 2H), 3.61-3.82 (m, 6H). .sup.13C NMR (CDCl.sub.3, 100 MHz): =155.1-155.0, 79.4-79.0, 75.3-75.0, 70.5-70.1, 69.8-69.3, 66.1-66.0. HR-MS (ESI) (M+H).sup.+ m/z Calcd. for C.sub.12H.sub.17O.sub.9: 305.0867. Found: 305.0879.
[0196] Pyridine Containing Cyclic Carbonates
[0197] Pyridine containing cyclic biscarbonate with ester linkage can be synthesized from pyridine containing dicarboxylic acids or esters with glycerol carbonate via standard esterification by or transesterification protocols e.g. catalytic esterification/transesterification or by using coupling agents. Pyridine containing cyclic carbonates with ether linkages can be synthesized from corresponding furan containing diols via alkylations using a cyclic carbonate containing halide or pseudo halide or epoxide containing halide or pseudo halide followed by CO.sub.2 insertion.
Example 4
Synthesis of Pyridine Based Cyclic Biscarbonate with Ester Linkage
[0198] The synthetic protocol for converting pyridine-2,5-dicarboxylic acid to bis((2-oxo-1,3-dioxolan4-yl)methyl)-pyridine-2,5-dicarboxylate is shown in Scheme 7.
##STR00045##
[0199] To a round bottom flask connected with condenser, pyridine-2,5-dicarboxylic acid (20 mmol, 3.34 g), SOCl.sub.2 (60 mmol, 7.14 g) and 5 mL of DMF were added and the reaction was carried out at 90 C. under argon for 4 h. The reaction mixture was then cooled down to room temperature, Et.sub.3N (6 equiv., 16.8 mL) and glycerol carbonate (80 mmol, 9.45 g in 12 mL of THF) were added slowly and was further heated at 90 C. overnight. After the reaction, the excess amount of Et.sub.3N, SOCl.sub.2 and solvent were removed under vacuum. The product bis((2-oxo-1,3-dioxolan-4-yl)methyl)pyridine-2,5-dicarboxylate was isolated as a white solid, filtered and washed with water (30 mL, 2 times) and with Et.sub.2O (30 mL, 2 times) to give 4.61 g (12.6 mmol) of pure product (63%) which was characterized by .sup.1H, .sup.13C-NMR and HRMS. .sup.1H-NMR (CDCl.sub.3, 400 MHz): 9.19 (dd, J=2.1, 0.8 Hz, 1H), 8.49 (dd, J=8.2, 2.2 Hz, 1H), 8.21 (dd, J=8.1, 0.8 Hz, 1H), 5.36-5.05 (m, 2H), 4.84-4.31 (m, 8H). .sup.13C NMR (CDCl.sub.3, 100 MHz): =168.8, 168.6, 159.9, 159.8, 155.5, 155.4, 143.8, 133.2, 130.3, 79.4, 79.3, 71.4, 71.3, 70.2, 70.1. HR-MS (ESI) (M+H).sup.+ m/z Calcd. for C.sub.15H.sub.14NO.sub.10: 368.0612. Found: 368.0610.
Example 5
Process Improvement for FBC-1
Synthesis of Furan Based Cyclic Biscarbonate with Ester Linkage
[0200] ##STR00046##
[0201] Preparation of FDCA chloride in THF solution: To a round bottom flask connected with condenser, 2,5-furandicarboxylic acid (FDCA) (12.5 g, 80 mmol), thionyl chloride (SOCl.sub.2) (14 mL, 192 mmol) and catalytic amount of DMF (0.1 mL) were added and the reaction was carried out at 90 C. under argon for 4 h. Excess of SOCl.sub.2 were removed under vacuum. Then the residue solid was redissolved in 40 mL anhydrous THF.
[0202] To a solution of trimethylamine (Et.sub.3N) (200 mmol, 27.9 mL) and glycerol carbonate (23.6 g, 100 mmol) in 250 ml of anhydrous THF were added slowly to the FDCA chloride in THF solution (40 mL) at 0 C. After stirring at room temperature for 3 h, the reaction was further heated to 90 C. for 18 h. The reaction was quenched by addition of water (100 mL). The product bis((2-oxo-1,3-dioxolan-4-yl)methyl)furan-2,5-dicarboxylate was precipitated out as a white solid. The solid was filtered and washed with water (2*50 mL) and with THF (2*50 mL) to give FBC-1 in 25.8 g (72.4 mmol, 90% yield) which was characterized by .sup.1H, .sup.13C-NMR and HRMS.
[0203] .sup.1H-NMR (DMSO, 400 MHz): 7.42 (s, 2H), 5.16 (m, 2H), 4.6 (m, 6H), 4.4 (dd, J=8.6, 6.1 Hz, 2H). .sup.13C NMR (DMSO, 100 MHz): =156.7, 154.6, 145.8, 119.6, 74.1, 67.0, 64.5. HRMS (ESI) (M+H).sup.+ m/z Calcd. For C.sub.14H.sub.12O.sub.11: 357.0452. Found: 357.0459.
Example 6
Process Improvement for FBC-2
Optimized Synthesis of Furan Based Cyclic Biscarbonate with Ether Linkage
[0204] The scale up and optimized synthesis of cyclic biscarbonate 4,4-(((furan-2,5-diylbis(methylene))bis(oxy))bis(methylene))bis(1,3-dioxolan-2-one), FBC-2, is shown in Scheme 9. The yield of the first step di-alkylation was increased by changing the phase transfer catalyst from tetrabutylammonium bromide to tetrabutylammonium hydrogen sulfate (TBHS). In addition, the reaction was carried out at room temperature.
##STR00047##
[0205] To a solution of sodium hydroxide solution (1:2 w/w) was added with furandimethanol (FDM) (10.2 g, 80 mmol) and 10 mol % of tetrabutylammonium hydrogen sulfate (2.7 g, 8.0 mmol). The reaction mixture was cooled to 0 C., epichlorohydrin (32.5 mL, 400 mmol) was added dropwise over 30 min. The mixture was stirred at room temperature for 16 h. The reaction was quenched by addition of water (50 mL). The aqueous layer was extracted with pentane (10 mL) to remove excess epichlorohydrin. Then the aqueous layer was extracted with EtOAc (4*30 mL). The combined EtOAc extracts were washed with water (30 mL) and were allowed to pass through a short pad of silica gel. The solvent was evaporated to obtain a pure yellow oil diepoxy product 2,5-bis((oxiran-2-ylmethoxy)methyl)furan in 18.4 g (76 mmol, 95% yield) and characterized by .sup.1H and .sup.13C NMR.
[0206] In the second step, the diepoxy product 2,5-bis((oxiran-2-ylmethoxy)methyl)furan (8.6 g, 36 mmol), tetrabutyl ammonium iodide (TBAI) (0.66 g, 1.8 mmol, 5 mol %) and pyridinedimethanol (0.25 g, 1.8 mmol, 5 mol %) were dissolved in 20 mL of anhydrous THF, transferred into a Parr reactor and pressurized with CO.sub.2 up to 150 psig after purging with N.sub.2 followed by CO.sub.2. The reaction was carried out under stirring at 105 C. for 24 h. After the reaction, the reactor was cooled to room temperature and depressurized. The solvent THF was removed and the mixture was redissolved in 200 mL of EtOAc. The organic layer was washed with sodium thiosulfate (3*20 mL) to remove the iodine followed by brine (2*20 mL). The organic layer was separated and dried by sodium sulfate. Then the volume of EtOAc was reduced to 20 mL and a white solid was precipitated out. The solid was filtered, collected and washed with pentane (3*20 mL). The solid was dried in an oven under vacuum at 60 C. for 24 h. The bicarbonate product 4,4-(((furan-2,5-diylbis(methylene))bis(oxy))-bis(methylene))bis(1,3-dioxolan-2-one) was isolated as a white solid (10.6 g, 32.3 mmol, 90% yield) and characterized by .sup.1H NMR.
Example 7
Multigram Scale Synthesis of 2,5-bis((oxiran-2-ylmethoxy)methyl)furan
[0207] To a solution of sodium hydroxide in water (30 g in 60 mL), furan-2,5-diyldimethanol (20 g, 156 mmol), and tetrabutylammonium hydrogen sulfate (5.3 g, 1.60 mmol) was added and the mixture was cooled to 0 C. followed by addition of epichlorohydrin (65 mL, 1020 mmol) dropwise over 30 min. The mixture was then stirred at room temperature for 16 h. Deionised water (50 mL) was added and the mixture was extracted with ethyl acetate (360 mL). The extracts were passed through a pad of silica gel using ethyl acetate:petroleum ether (1:1) as eluent and concentrated under reduced pressure. Product was obtained as a yellow liquid (31.1 g, 81%).
Example 8
Multigram Scale Synthesis of FBC-2 Under Optimized Conditions
[0208] 2,5-bis((oxiran-2-ylmethoxy)methyl)furan (50 g, 208 mmol) and tetrabutylammonium bromide (TBABr) (2 g, 6.24 mmol) were dissolved in 135 mL of dry THF and transferred into a Parr reactor. The reactor was purged with N.sub.2 followed by CO.sub.2 and then pressurized with CO.sub.2 up to 18 bar. The reaction was carried out under stirring at 75 C. for 18 h. After the reaction, the reactor was cooled to room temperature and depressurized. THF was removed under reduced pressure and the crude product was then dissolved in ethyl acetate and filtered to afford the pure white product and a dark brown solution. Dark brown filtrate was passed through a pad of silica gel using ethyl acetate: petroleum ether (2:1) as eluent and solvent removed under reduced pressure to afford the remaining product (59 g, 86%).
Example 9
Synthesis of Pyridine Based Cyclic Biscarbonate with Ester Linkage
[0209] ##STR00048##
[0210] Preparation of pyridine-2,6-dicarboxylic acid chloride in DMF solution: To a round bottom flask connected with condenser, pyridine-2,6-dicarboxylic acid (3.68 g, 40 mmol), thionyl chloride (SOCl.sub.2) (8.7 mL, 120 mmol) and 3 mL of DMF (catalytic amount) were added and the reaction was heated at 80 C. under argon for 3 h. After that a colorless solution was obtained. The solvent together with excess thionyl chloride were removed under vacuum. The remained pyridine-2,6-dicarboxylic acid chloride was redissolved in 10 mL of anhydrous DMF.
[0211] To a solution of the reaction mixture of Et.sub.3N (50.3 mL, 360 mmol) and glycerol carbonate (14.2 g, 120 mmol) in 150 mL of THF were added slowly the pyridine-2,6-dicarboxylic acid chloride in DMF solution at 0 C. After stirring at room temperature for 3 h, the reaction was heated at 80 C. for 18 h. The reaction was quenched by addition of water (100 mL). The product bis((2-oxo-1,3-dioxolan-4-yl)methyl)-pyridine-2,6-dicarboxylate was precipitated out from reaction mixture. The solids were collected, filtered and washed with water (2*50 mL) and with THF (2*50 mL) to give 10.6 g (26.3 mmol) of off-white solids (72% yield) which were characterized by .sup.1H-NMR, .sup.13C-NMR and HRMS. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.43-8.08 (m, 3H), 5.27-5.10 (m, 2H), 4.77-4.52 (m, 6H), 4.45 (dd, J=8.6, 6.2 Hz, 2H); .sup.13C NMR (101 MHz, DMSO-d.sub.6) 163.4, 154.8, 147.4, 139.6, 128.4, 74.3, 66.2, 64.9 HR-MS (ESI.sup.+): Calcd. for C.sub.15H.sub.13NO.sub.10 [M+Na].sup.+: 390.0432; Found: 390.0450.
Example 10
Synthesis of Novel Hydroxypolyurethanes (PHUs)
[0212] Linear hydroxypolyurethane structures were synthesized by polyaddition of the prepared cyclic biscarbonates with various readily available diamines, as shown in Scheme 11.
##STR00049##
##STR00050##
##STR00051##
[0213] In the synthesis of PHUs of the present application, the cyclic biscarbonate (e.g. 250 mg) and two drops of mesitylene (as internal standard) were taken into a (e.g. 10 ml) glass reactor and the content was dissolved in anhydrous DMF (e.g. 0.5 or 1 ml) while stirring on an oil bath at 70 C. (oil bath temperature). The solution was then purged with nitrogen for 15-20 min. A solution of the diamine (1 mol equiv) was prepared separately in anhydrous DMF, purged with nitrogen and charged into the reaction tube to initiate the reaction.
[0214] For polymerizations using less soluble diamines (e.g. XDA), the diamine was first dissolved in dry DMF at 70 C. and then equimolar quantity of cyclic biscarbonate monomer solution (nitrogen purged) was added to it. Reaction mixture was then allowed to stir for 48 h. Time to time samples were collected by syringe to monitor monomer conversion by .sup.1H NMR spectroscopy. Finally, the reaction mixture was cooled down to room temperature and the polymer was precipitated using excess diethyl ether. Light brown polymer was then dried under air followed by heating at 80 C. in high vacuum oven. A small amount of polymer was re-dissolved in small amount of dry DMF, re-precipitated using ether and dried before the final characterization by gel permeation chromatography (GPC) using DMF as eluent and NMR spectroscopy.
[0215] Polymer Characterization
[0216] .sup.1H NMR spectra were recorded on a 400 MHz Bruker Ultra-Shield AVANCA 400SB spectrometer. Mesitylene or residual solvent peaks were used as internal standard.
[0217] Number average molecular weight (Mn), peak molecular weight (Mp) and polydispersity index (PDI) analysis of polymers synthesized according to the method disclosed herein were performed in size exclusion chromatography (SEC) systems using DMF as solvent. The DMF GPC system was equipped with Waters 515 HPLC pump, Waters 717 plus autosampler, Waters 2414 refractive index (RI) detector, two PLgel 5 m mixed-C columns. The eluent flow rate was 0.8 ml/min and the columns were maintained at 50 C. The injected sample solution concentration was 5 mg/ml and injected volume was 50 l.
[0218] The details of the polymerization conditions and GPC data of the PHUs synthesized according to the method disclosed herein are provided in Table 1 as follows.
TABLE-US-00001 TABLE 1 Details of polymerization conditions and GPC data of the PHUs synthesized according to the method disclosed herein. Monomer GPC (DMF).sup.b PHU Bis- Bis- Conversion Mn, Mp, Tg, code carbonate amine (%) g/mol g/mol PDI C. BP75 FBC1 FBA >98 3200 3750 1.31 44 BP76 FBC1 DAP >99 3900 5400 1.37 22 BP77 FBC1 XDA >81 2700 2600 1.35 51 BP78 PBC1 FBA >99 3100 3600 1.32 34 BP79 PBC1 DAP >99 3950 4900 1.41 10 BP80 PBC1 XDA 52 2450 2050 1.40 67 BP81 FBC2 FBA >95 2650 3400 1.49 14 BP82 FBC2 DAP >99 3400 6300 1.85 BP83 FBC2 XDA 59 2500 2900 1.74 12 BP89 FBC2 HMDA >98 8000 11600 1.45 7 BP84 HFBC DAP >99 2350 2000 1.24 18 BP85 HFBC FBA >99 2412 2129 1.18 18 BP86 HFBC XDA >99 2659 2381 1.23 23 BP90 FBC1 HMDA 99 4100 5250 1.49 19
[0219] .sup.1H NMR spectra (in DMSO-d.sub.6) of polyhydroxyurethanes (PHUs) obtained using different bis-carbonate and bis-amine monomers according to the method disclosed herein are provided in
[0220] GPC chromatogram of polyhydroxyurethanes (PHUs) obtained by the polymerization of FBC-2 and FBA is provided in
Example 11
Polymerisation of FBC-2 Obtained from Example 6 with Diamine (DAP/HMDA)
[0221] FBC-2 and two drops of mesitylene (as internal standard) were taken into a glass tube and the content was dissolved in anhydrous DMF while stirring on an oil bath at 70 C. (oil bath temperature). The solution was then purged with nitrogen for 15-20 min. A solution of the diamine (1 equiv) was prepared separately in anhydrous DMF, purged with nitrogen and charged into the reaction tube to initiate the reaction. Reaction mixture was then allowed to stir for 24 h. Time to time samples were collected by syringe to monitor monomer conversion by .sup.1H NMR spectroscopy. Finally, the reaction mixture was cooled down to room temperature and the polymer was precipitated using excess diethyl ether. Light brown polymer obtained was then dried under air followed by heating at between 60 to 70 C. in high vacuum oven. A small amount of polymer was re-dissolved in small amount of dry DMF, re-precipitated using ether and dried before the final characterization by GPC (DMF eluent) and NMR spectroscopy.
[0222] The details of the polymerization conditions and GPC data for FBC-2 based PHUs are provided in Table 2 as follows.
TABLE-US-00002 TABLE 2 Details of polymerization conditions and GPC data for FBC-2 based PHUs Bis- GPC Polymer Solvent FBC-2 Amine Conversion Mn, Mp, Code (mL) (mg) (mg) (%) g/mol g/mol PDI BP122 DMF (3) 2000 DAP >99 14800 23300 1.7 (616.8) BP129 DMF (0.75) 500 DAP >99 14400 22500 1.8 (154.2) BP136 DMF:MeOH 300 DAP >99 16340 27160 1.8 (3:1) (0.5) (92.5) BP138 DMF (1) 300 HMDA 85 10020 15830 1.7 (106.2)
Example 12
Gram Scale Polymerisation of FBC-2 with DAP
[0223] FBC-2 and two drops of mesitylene (as internal standard) were taken into a glass tube and the content was dissolved in anhydrous DMF while stirring on an oil bath at 70 C. (oil bath temperature). The solution was then purged with nitrogen for 15-20 min. A solution of the diamine (1 mol equiv) was prepared separately in anhydrous DMF, purged with nitrogen and charged into the reaction tube to initiate the reaction. Reaction mixture was then allowed to stir for 28 h. Time to time samples were collected by syringe to monitor monomer conversion by .sup.1H NMR spectroscopy. Finally, the reaction mixture was cooled down to room temperature and the polymer was precipitated using excess diethyl ether. Light brown polymer obtained was then dried under air followed by heating at 70 C. in high vacuum oven. A small amount of polymer was re-dissolved in small amount of dry DMF, re-precipitated using ether and dried before the final characterization by GPC (DMF eluent), DSC (Tg=14-20 C.) and NMR spectroscopy. The details of the polymerization conditions and GPC data for the gram scale synthesis of FBC-2 based PHU are provided in Table 3 as follows. The GPC chromatogram of PHU obtained by the polymerization of FBC2 and DAP is provided in
TABLE-US-00003 TABLE 3 Details of polymerization conditions and GPC data for the gram scale synthesis of FBC-2 based PHU Bis-Amine GPC Polymer Solvent FBC-2 DAP Conversion Mn, Mp, Code (mL) (g) (g) (%) g/mol g/mol PDI BP142 DMF (15) 9.85 3.07 >99 11130 17380 1.8 BP147 DMF (30) 19.8 6.15 >99 11190 17170 1.9
Example 13
Polymerization of FBC-2 with DAP at 60 g Scale
[0224] FBC-2 (60 g, 183 mmol) was dissolved in 70 mL of dry DMF in a 500 mL two neck flask. The flask was purged with argon gas and heated to 70 C. Mesitylene was added as an internal reference and a small sample of mixture was taken to be analysed by .sup.1H NMR and labelled as 0 h. Pentane-1,5-diamine [DAP] (18.7 g, 183 mmol) was dissolved in 20 mL of DMF and added into round bottom flask. The reaction was stirred for 28-52 h with sample being taken at 1 h, 3 h, 6 h, 24 h, 28 h for NMR analysis. Reaction mixture was added drop by drop into glass bottle containing diethyl ether (200 mL) with stirring. Product was washed further with diethyl ether (2200 mL) before drying overnight in a vacuum oven at 60 C. (75 g, 95%). GPC: Mn 12731 g/mol, Mp 19103 g/mol, PDI 1.8.
Example 14
Polymerisation of PBC-2 Obtained from Example 9 with Diamine (FBA/DAP)
[0225] PBC-2 and two drops of mesitylene (as internal standard) were taken into a glass tube and the content was dissolved in anhydrous DMF while stirring on an oil bath at 70 C. (oil bath temperature). The solution was then purged with nitrogen for 15-20 min. A solution of the diamine (1 equiv) was prepared separately in anhydrous DMF, purged with nitrogen and charged into the reaction tube to initiate the reaction. Reaction mixture was then allowed to stir for 48 h. Time to time samples were collected by syringe to monitor monomer conversion by .sup.1H NMR spectroscopy. Finally, the reaction mixture was cooled down to room temperature and the polymer was precipitated using excess diethyl ether. Light brown polymer was then dried under air followed by heating at 70 C. in high vacuum oven. A small amount of polymer was re-dissolved in small amount of dry DMF, re-precipitated using ether and dried before the final characterization by GPC (DMF eluent) and NMR spectroscopy.
[0226] The details of the polymerization conditions and GPC data for PBC-2 based PHU are provided in Table 4 as follows.
TABLE-US-00004 TABLE 4 Details of polymerization conditions and GPC data for PBC-2 based PHUs GPC Polymer Solvent PBC-2 Bis-Amine Conversion Mn, Mp, Code (mL) (mg) (mg) (%) g/mol g/mol PDI BP125 DMF (3.5) 500 FBA (174) >99 2740 3170 1.3 BP126 DMF (3) 500 DAP (141) >99 4230 4810 1.3
[0227] Post-Functionalization of Polyhydroxyurethanes
[0228] The novel PHUs obtained can be further functionalized through the hydroxyl group to achieve new functionalized PHUs having desired properties such as hydrophilicity, hydrophobicity, oil solubility and dispersibility in water and oil for various applications. The functionalization could lead to neutral, anionic, cationic or zwitterionic polymers. This strategy could also be applied to any polyhydroxyurethanes obtained through the reaction between any bis/multi-carbonate and any bis/multi-amine and the corresponding obtained PHU having one or more unfunctionalised primary or secondary hydroxyl groups. The functionalization strategy includes, but is not limited to esterification, sulphonylation, phosphorylation, zwitterion formation, grafting suitable molecular entities/oligomers/polymers, etc. The following examples illustrate the said component of the invention.
[0229] Anionic Isocyanate Free Polyurethanes
[0230] The hydroxyl groups of the PHUs were functionalized introducing anionic phosphate ester or alkylsulfonate groups as pendants. The counter cations can be varied and the degree of functionalization optimized to modify solubility, dispersion and crosslinking characteristics of the PHUs in water at different pHs as well as in various organic solvents.
Example 15
Synthesis of PHU-Organophosphate Monoester
[0231] ##STR00052##
[0232] To a solution of a representative PHU (1.00 g) in anhydrous DMF (5 mL) and acetonitrile (1 mL) mixture was added with the desired amount of trichloroacetonitrile (TCAN, 1.1 equiv. to TBAP). Desired amount of tetra-n-butylammonium dihydrogen phosphate (TBAP) was dissolved separately in anhydrous acetonitrile (1 mL) and added into the polymer solution dropwise. The reaction mixture was stirred at room temperature for 18 h. Solvent was removed under reduced pressure and the residue was re-dissolved in a small amount of acetonitrile (1 mL). The phosphate-functionalized PHU was precipitated out using diethyl ether (10 mL) as anti-solvent. Characterization was done using .sup.1H and .sup.31P NMR (DMSO-d.sub.6), TGA, DSC and DLS (Table 5). .sup.1H NMR showed n-butyl peaks at 1.57, 1.32 and 0.93 ppm. Multiple peaks between 2.00-10.00 ppm were observed in .sup.31P NMR. Preliminary solubility data are demonstrated in Table 6.
TABLE-US-00005 TABLE 5 Synthesis of PHU-organophosphate monoester and their characterization studies TGA at 5% DLS % of hydroxyl loss under DSC Particle DLS Zeta TBAP groups Yield N.sub.2 Tg, size potential Polymer (mg) phosphorylated.sup.a (%) ( C.) ( C.) (nm) (mV) FBC2 + 143 5 >99 219 28 n.d n.d DAH 340 15 >99 180 25 218 55 1710 50 56 172 36 n.d n.d .sup.a(determined from .sup.1H NMR using furanyl proton as reference)
TABLE-US-00006 TABLE 6 Solubility of representative PHU-organophosphate monoesters % of hydroxyl groups Solubility Polymer phosphorylated.sup.a pH 4 pH 7 pH 9 DMF MeOH THF Acetone FBC2 + 5
Dispersed
DAP 15 Dispersed Dispersed Dispersed
Dispersed
50
.sup.a(determined from .sup.1H NMR using furanyl proton as reference)
Example 16
Functionalization of PHUs with Alkyl Sulfonate
[0233] ##STR00053##
[0234] To a solution of a representative PHU (1.00 g) (Table 7) in anhydrous DMF (5 mL) was added with 1,4-butane sultone (1.1 equiv). 60% sodium hydride in oil (1.1 equiv) was then slowly added to the reaction mixture at room temperature and was stirred at room temperature for about 30 min before heating up to 60 C. and stirred for another 24 h. The reaction mixture was cooled to 0 C. and 20 mL methanol was added to quench the reaction. After the solvent was removed under reduced pressure and the solid was washed with diethyl ether (310 mL) characterization/preliminary solubility studies were done using .sup.1H NMR in DMSO-d.sub.6 with butyl peaks observed at 1.73 and 1.73 ppm (Tables 7 and 8).
TABLE-US-00007 TABLE 7 Details on the functionalization of PHU with 1,4-butane sultone 1,4-butane 60% NaH sultone % of hydroxyl groups Yield Polymer (mg) (L) sulfonated.sup.a (%) FBC2 + DAP 36 92 6 >99 132 338 42 >99 .sup.a(determined from .sup.1H NMR using furanyl proton as reference)
TABLE-US-00008 TABLE 8 Solubility of representative PHUs with pendant n-butyl sulfate groups % of hydroxyl groups Solubility Polymer sulfonated.sup.a pH 4 pH 7 pH 9 DMF MeOH THF Acetone FBC2 + 6 Dispersed Dispersed Dispersed Dispersed
DAP 42
Dispersed
.sup.a(determined from .sup.1H NMR using furanyl proton as reference)
Example 17
Representative Procedure for the Synthesis of Phosphocholine Functionalized PHUs
[0235] To a representative PHU based on FBC-2 and DAP (0.215 g, 0.50 mmol) in anhydrous DMF (5 mL) solution, triethylamine (0.080 g, 0.80 mmol) was added followed by ethylene chlorophosphate (0.072 g, 0.50 mmol) at room temperature. After stirring the reaction at RT for 18 h, the solvent was removed and the product precipitated using water. The precipitate obtained was washed with water (310 mL) and with diethyl ether. Based on the .sup.1H NMR, the hydroxyl groups in the PHU were completely reacted. In .sup.31P NMR a single phosphorous peak was observed at 15.8 ppm. Phosphocholine functionalized PHUs can be obtained by the reaction of this product with trimethylamine.
Post Functionalization of PHUs Using Amino Acids to Form Novel Types of Amino and Thiol Functionalized PHUs
[0236] PHUs can be functionalized with amino acids or peptides or proteins by any standard esterification protocols introducing amino and thiol pendant groups. The degree of functionalization can be tuned. The thiol groups can facilitate reversible self-crosslinking or cross linking with other substrates such as peptides by disulfide chemistry.
##STR00054##
Example 18
Procedure for Esterification of PHUs with Amino Acid Chloride Hydrochloride
[0237] A representative PHU based on FBC-2 and DAP (0.1 g, 0.23 mmol) in anhydrous DMF (5 mL) solution was added to the desired amino acid chloride hydrochloride (0.5 mmol) in DMF followed by (0.21 mL, 1.50 mmol) triethylamine at room temperature. After 18 h of stirring, the reaction was stopped and subjected to different methods of work-up.
[0238] Method A: 10 mL of water was added to quench the reaction. After removing the solvent, the residue obtained was dissolved in water (5 mL). The aqueous layer was washed with ethyl acetate (310 mL) and evaporated to dryness under reduced pressure and then re-dissolved in small amount of acetone (1 mL). The functionalized PHU was precipitated out using diethyl ether (10 mL) as anti-solvent.
[0239] Method B: 10 mL of water was added at ambient temperature to quench the reaction. After removing the solvent, the residue obtained was dissolved in DCM (5 mL) and was washed with dilute bicarbonate solution (10 mL) followed by water (10 mL). The organic layer was separated and dried with sodium sulfate, filtered and evaporated to dryness under reduced pressure. The residue was re-dissolved in DCM (1 mL). The functionalized PHU was precipitated out using diethyl ether (5 mL) as anti-solvent.
[0240] Method C: 10 mL of water was added at ambient temperature to quench the reaction. The polymer precipitated out from the reaction was collected by filtration. The polymer was redissolved in DMF (1 mL) and chloroform was used as anti-solvent to re-precipitate the polymer which was then dried under vacuum (1.18 g (yield 88%)) as a brown syrup. Characterization was done using .sup.1H NMR.
TABLE-US-00009 TABLE 9 .sup.1H NMR characterization of PHUs functionalized with amino acids Method for .sup.1H NMR Amino acid work-up characterization glycine A glycine peak: 3.44 ppm in CD.sub.3OD D-phenylalanine B aromatic ring of D-phenylalanine peak: 7.25 ppm in CDCl.sub.3 N-acetyl C N-acetyl peak observed as a Cysteine singlet at 1.98 ppm in DMSO-d.sub.6
[0241] Hydrophobic Isocyanate Free Polyurethanes
[0242] The introduction of pendant medium and long chain alkyl or alkenyl or arylalkyl or arylalkenyl functionalities to PHUs by esterification using fatty acid/or carboxylic acid derivatives by standard esterification protocols resulting in hydrophobic isocyanate free polyurethanes which are oil soluble/dispersible and air/photo/thermo crosslinkable and photoreversibly crosslinkable is reported herein.
Example 19
Synthesis of Fatty Acid Esters of PHUs
[0243] A representative PHU based on FBC-2 and DAP (1.00 g, 2.3 mmol) in anhydrous DMF (25 mL) solution was added to the desired acylation reagent (5.0 mmol) followed by (1.05 mL, 7.5 mmol) triethylamine at room temperature. After 24 h of stirring, 10 mL of water was added to quench the reaction. After removing the solvent, the residue obtained was dissolved in DCM (30 mL). The organic layer was washed with dilute bicarbonate solution (20 mL) followed by water (20 mL). The organic layer was separated and dried over sodium sulfate, filtered and evaporated to obtain the expected product.
##STR00055##
TABLE-US-00010 TABLE 10 .sup.1H NMR characterization of PHUs functionalized with acylation reagent .sup.1H NMR Pendant Yield Mn, characterization Entry group (%) g/mol PDI in CDCl.sub.3 1 Butyric acid 96 6440 2.1 Butyl peak: 2.25, 1.61, anhydride 0.91 ppm 2 Palmitic acid 95 4630 2.3 Palmityl peak: 2.28, chloride 1.58, 1.41, 1.25, 0.87 ppm 3 Cinnamic acid 97 5920 2.2 Cinnamate alkene peak: chloride 6.41 ppm 4 Oleic acid 93 10070 1.8 Oleyl alkene peak: chloride 5.32 ppm 5 Linoleic acid 94 12070 2.9 Linoleyl alkene peak: chloride 5.35 ppm
Example 20
Modification of PHUs with Lactide
[0244] ##STR00056##
[0245] To a representative PHU based on FBC-2 and DAP (1.00 g, 2.5 mmol) in anhydrous DMF (10 mL) solution, lactide (1.08 g, 7.5 mmol) and DMAP (15 mg, 0.1 mmol) were added at room temperature. After 48 h of stirring at 80 C., the solvent was removed and the residue was subsequently dissolved in DCM (5 mL) and precipitated out using diethyl ether as the anti-solvent (10 mL). The product is subsequently washed two times with diethyl ether and dried to obtain the product (1.0 g, 58%). Characterization was done using .sup.1H NMR in MeOH-d4 (Lactyl peaks observed at 5.16, 4.22 and 1.2 ppm) and GPC (Mn=8890 g/mol, Mp=10950 g/mol, PDI=1.6.)
[0246] PHU Graft Polymers
[0247] Different types of polymers can be grafted from or to PHUs resulting in novel functional materials. In one of these approaches exemplified herein, polymers were grafted from PHUs by ring opening polymerization using lactide and lactone to form PHU-graft co-polymers. Other types of ROP using lactams, cyclic carbonates are also possible. An example for the graft to approach can be demonstrated using grafting PDMS to PHUs resulting in new functional PHUs, which can be used in anti-smudge coatings. An example on using furan based PHUs for grafting via Diel's-Alder reaction (DA reaction) is also demonstrated. Similarly, peptides or proteins can also be grafted to PHUs resulting in stimuli responsive active delivery, functional coatings materials for biomedical devices etc. For example, DA reaction of maleimide functionalized peptides or proteins to furan based PHUs or coupling of cysteine modified PHU with peptides containing cysteine residue by disulfide chemistry.
Example 21
Ring Opening Polymerization (ROP) of Lactide from PHUs to Form PHU-q-PLA
[0248] ##STR00057##
[0249] To a representative PHU based on FBC-2 and DAP (1.00 g, 2.5 mmol) in anhydrous DMF (10 mL) solution, lactide (9.08 g, 63 mmol) and DMAP (26 mg, 0.5 mmol) were added at room temperature. After 48 h of stirring at 80 C., the solvent was removed and the residue was subsequently dissolved in DCM (5 mL) and precipitated out using diethyl ether as the anti-solvent (10 mL). The product is washed two times with diethyl ether and dried to obtain the product (3.3 g, 90%). Characterization was done using .sup.1H NMR in CDCl.sub.3 with lactyl peaks observed at 5.16, 4.10, 1.56 & 1.48 ppm and GPC: Mn=28940 g/mol, Mp=36770 g/mol, PDI=1.4.
Example 22
Grafting Caprolactone from PHUs to Form PHU-c-PCL
[0250] ##STR00058##
[0251] To a solution of a representative PHU based on FBC-2 and DAP (2.00 g) in anhydrous DMF (10 mL) s-caprolactone (16 g, 30 equiv) and trifluromethanesulfonimide (132 mg, 0.1 equiv) were added and the reaction mixture was stirred at 50 C. for 48 h. Solvent was removed under reduced pressure and the product re-dissolved in small amount of chloroform (2 mL). Product was precipitated out using diethyl ether (10 mL) as anti-solvent. Characterization was done using .sup.1H NMR in CDCl.sub.3 with caproyl peaks observed at 4.05, 2.03, and 1.6
Example 23
Grafting PDMS to PHUs to Form PHU-q-PDMS
[0252] ##STR00059##
[0253] To a 50 mL reaction flask filled with Argon was added oxalyl chloride (COCl).sub.2 (1.0 mL, 11.6 mmol). Subsequently, hydroxyl-terminated polydimethylsiloxane (Mn4670) PDMS-OH (1.1 mL, 0.228 mmol) was added dropwise into the oxalyl chloride. The reaction mixture was allowed to stir at room temperature for 12 h. Unreacted oxalylchloride and volatile impurities were removed by keeping the reaction mixture under vacuum at room temperature for 1 h and at 45 C. for 4 h to yield PDMS-OCOCOCl as a clear liquid.
[0254] In the next step, a representative PHU polymer based on FBC-2 and DAP (107.5 mg) was dissolved in anhydrous DMF (5.0 mL) followed by addition of 2 mL THF solution of PDMS-OCOCOCl. The reaction mixture was stirred at room temperature for 48 h and quenched with 1 mL of water. The solvent was removed under vacuum and the residue redissolved in 20 mL of chloroform and was washed with bicarbonate solution (10 mL) followed by water (10 mL). After concentrating this solution to 5 mL, the petroleum ether was added to precipitate out 310 mg (58% yield) of the product as a yellow syrup. Characterization was done using .sup.1H NMR in CDCl.sub.3 with siloxane peak observed as large board singlets at 0.03 ppm and the furan peak was observed as a singlet at 6.26 ppm.
Example 24
Representative Procedure for Grafting PLA to PHU Via Diel's Alder (DA) Reaction
[0255] ##STR00060##
[0256] To a solution of a representative PHU based on FBC-2 and DAP (120 mg, 0.106 mmol based on mole of furan) in DMF (1 mL) was added PLA-M (90 mg, Mn-2000, 0.01 mmol based on mole of maleimide). The reaction mixture was stirred at 50 C. for 6 hours. After cooling to room temperature, the reaction mixture was added into diethyl ether to precipitate the polymer. The crude polymer was washed with ethyl acetate to remove the unreacted PLA-M. The purified polymer was obtained as white solid (85 mg, yield 40%). .sup.1H NMR (400 MHz, DMSO) 7.11 (br, 2H), 6.37 (br, 2H), 6.34 (br, DA adduct peak), 5.21 (br, 2H), 5.01 (br, 1H), 4.81-4.68 (br, 1H), 4.38 (br, PLA peak), 3.92-3.74 (m, 5H), 3.51-3.21 (m, 8H), 2.93 (br, 4H), 1.47 (m, 6H), 1.36-1.10 (m, 8H).
APPLICATIONS
[0257] Various embodiments of the present disclosure provide a green and sustainable strategy to produce cyclic biscarbonates and polyhydroxyurethanes by using precursor compounds derived from a bio-based source. In various embodiments, the precursor compound, monomer and/or reaction product may be partially bio-based/bio-derived or fully bio-based/bio-derived. In various embodiments of the methods disclosed herein, the process does not involve the use of toxic isocyanates and phosgene, thereby making the production process friendly to the environment.
[0258] In various embodiments thereof, the compound (i.e. monomer) and reaction product (i.e. polymer) disclosed herein are high value products for specialty applications such as coating, foams and adhesives, which will not only further value-add bio-feedstocks supporting biorefineries but also provide alternative sustainable materials for future applications.
[0259] Various embodiments of the present disclosure provide non-isocyanate polyhydroxylurethanes (NIPUs/PHUs) having high thermal and hydrolytic stability, enhanced adhesion properties and are chemically resistant to non-polar solvents. Various embodiments of the present disclosure provide compounds that are capable of serving as monomers in a polymerization reaction and that comprise aromatic units that are atypical of cyclic biscarbonates known in the art. In various embodiments therefore, the reaction products of these monomers and polymers disclosed herein may be in the form of a new emerging class of functional isocyanate free polyurethanes and that can be used in a wide array of applications such as in the manufacturing of foams, solvent/water borne coating, adhesives in the building and construction, automotive, packaging, textiles, fibers, apparel, and electronics industry etc; in applications such as pigment/hydrophobic material dispersing agents, film formers, gelling agents, rheology modifiers, oil thickners etc; in personal care industry and in applications such as antifouling coating and drug delivery in biomedical industries. The present disclosure has demonstrated the principles involved, and opens the way for further scale-up in many applications.
[0260] It will be appreciated by a person skilled in the art that other variations and/or modifications may be made to the embodiments disclosed herein without departing from the spirit or scope of the disclosure as broadly described. For example, in the description herein, features of different exemplary embodiments may be mixed, combined, interchanged, incorporated, adopted, modified, included etc. or the like across different exemplary embodiments. The present embodiments are, therefore, to be considered in all respects to be illustrative and not restrictive.