ALTERNATING COPOLYMERS OF SELECTED UNSYMMETRICALLY SUBSTITUTED STILBENES AND MALEIC ANHYDRIDE OR N-SUBSTITUTED MALEIMIDES

Abstract

In one aspect, the disclosure relates to the production of alternating polymers of maleic anhydride or an N-substituted maleimide with a stilbene.

Claims

1. A method of preparing an alternating copolymer of formula (I): ##STR00015## wherein X and Y are independently selected from the group consisting of C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.5 haloalkyl, halogen, cyano, C(O)C.sub.1-C.sub.5 alkyl, C(O)OC.sub.1-C.sub.5 alkyl, amino, NH(C.sub.1-C.sub.5 alkyl), N(C.sub.1-C.sub.5 alkyl).sub.2, O(C.sub.1-C.sub.5 alkyl), and 1H-tetrazole, wherein each alkyl is independently selected; and wherein X and Y are simultaneously not the same, and wherein A and B are single bonds; the method comprising admixing a disubstituted stilbene of formula (II): ##STR00016## with maleic anhydride or an N-substituted maleimide, in a polymerization solvent, in the presence of a radical initiator, wherein the alternating copolymer of formula (I) is substantially homogeneously distributed in the polymerization solvent in which the alternating copolymer was prepared, wherein the absolute viscosity of a substantially homogeneous distribution and polymerization solvent admixture is from about 0.1 to 200 centipoises (cP) at 300° K.

2. The method of claim 1 wherein the compound of formula (I) reacts with maleic anhydride.

3. The method of claim 1 wherein the compound of formula (I) reacts with an N-substituted maleimide.

4. The method of claim 1 wherein a reversible addition-fragmentation transfer agent of trithiocarbonate structure Z-SC(S)S-R, where Z is an alkyl chain from 2 to 24 carbons, and R is a group that can fragment homolytically to form a stabilized radical, is admixed with the polymerization solvent.

5. The method of claim 4 wherein the Z-SC(S)S-R is selected from the group consisting of benzyl 2-(((dodecylthio)carbonothioyl)thio)-2-methylpropanoate, benzyl 2-(((dodecylthio)carbonothioyl)thio)propanoate, and 2-(((dodecylthio)carbonothioyl)thio)propanoic acid.

6. The method of claim 1 wherein X is para to bond A.

7. The method of claim 1 wherein Y is para to bond B.

8. The method of claim 1 wherein the alternating copolymer has a substantially monomodal molecular weight distribution.

9. The method of claim 1 wherein the alternating copolymer has a number average molecular weight (Mn) of from about 1 kilodaltons (kDa) to about 150 kDa.

10. The method of claim 1 wherein the dispersity index (Ð) is from about 1 to about 5.

11. A method of preparing an alternating copolymer of formula (Ib): ##STR00017## wherein X is selected from the group consisting of C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.5 haloalkyl, halogen, cyano, C(O)(C.sub.1-C.sub.5)alkyl, C(O)O(C.sub.1-C.sub.5)alkyl, amino, NH(C.sub.1-C.sub.5) alkyl), N((C.sub.1-C.sub.5)alkyl).sub.2, O(C.sub.1-C.sub.5)alkyl, and 1H-tetrazole, wherein each alkyl is independently selected, comprising admixiing maleic anhydride or an N-substituted maleimide, and a compound of formula (IIb): ##STR00018## in a polymerization solvent, in the presence of a radical initiator and in the presence of a reversible addition-fragmentation transfer agent, wherein the fragmentation transfer agent is a trithiocarbonate Z-SC(S)S-R, where Z is an alkyl chain from 2 to 24 carbons, and R is a group that can fragment homolytically to form a stabilized radical, is admixed with the polymerization solvent, wherein the alternating copolymer of formula 1a is substantially homogeneously distributed in the polymerization solvent in which the alternating copolymer was prepared and wherein the absolute viscosity of a substantially homogeneous distribution and polymerization solvent admixture is from about 0.1 to 200 centipoise (cP) at 300° K.

12. The method of claim 11 wherein the trithiocarbonate Z-SC(S)S-R is selected from the group consisting of benzyl 2-(((dodecylthio)carbonothioyl)thio)-2-methylpropanoate, benzyl 2-(((dodecylthio)carbonothioyl)thio)propanoate, and 2-(((dodecylthio)carbonothioyl)thio)propanoic acid.

13. The method of claim 11 wherein X is OCH.sub.3.

14. The method of claim 11 wherein M.sub.n is from about 1 to about 150 kDa.

15. The method of claim 11 wherein Ð is from about 1 to about 5.

16. A method of preparing an alternating copolymer of formula (III): ##STR00019## wherein R.sub.10 is alkyl, comprising admixing a stilbene of formula (IV): ##STR00020## with maleic anhydride or an N-substituted maleimide, in a polymerization solvent comprising anhydrous anisole, in the presence of a radical initiator, wherein the alternating copolymer of formula (III) is substantially homogeneously distributed in the polymerization solvent in which the alternating copolymer of formula III is prepared and wherein the absolute viscosity of the substantially homogeneous distribution in the polymerization solvent is from about 0.1 to 200 centipoise (cP) at 300° K.

17. The method of claim 16 wherein R.sub.10 is CH.sub.3.

18. The method of claim 16 wherein Ð is from about 1 to about 5.

19. An alternating copolymer prepared by the method of claim 1

20. An alternating copolymer prepared by the method of claim 16.

Description

B. EXAMPLES

[0118] The following examples are put forth to provide those of ordinary skill in the art with a complete disclosure and description of how the compounds, compositions, articles, devices and/or methods claimed herein are made and evaluated and are intended to be purely exemplary of the disclosure and are not intended to limit the scope of what the inventors regard as their disclosure. Efforts have been made to ensure accuracy with respect to numbers (e.g., amounts, temperature, etc.), but some errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, temperature is in ° C. or is at ambient temperature, and pressure is at or near atmospheric.

[0119] Comparative Example 1: The copolymerization of (E)-4-methylstilbene (0.99 g, 5.1 mmol) with maleic anhydride (0.50 g, 5.1 mmol) in the presence of the radical initiator AIBN (0.015 g, 1 wt %) in tetrahydrofuran (anhydrous, 10 mL) at 60 ° C. results in gelation after 2-3 hours. The gelled polymerization solution is precipitated to a white solid by slowly adding to hexanes and vacuum filtering. A yield of 0.46 g (31% yield) was obtained. The resulting copolymer is not completely THF soluble but is chloroform soluble; a slightly opaque solution results from dissolving the copolymer in THF. The copolymer (0.5 g) was also soluble in refluxing aqueous sodium hydroxide (10.0 N, 50 mL) after 24 hours. Poly((E)-4-methylstilbene-alt-maleic anhydride) was effective in the extraction of proteins from protein membranes1.

[0120] Comparative Example 2: The copolymerization of (E)-4,4′-dimethylstilbene (1.03 g, 5.0 mmol) with maleic anhydride (0.49 g, 5.0 mmol) in the presence of the radical initiator AIBN (0.015 g, 1 wt %) in tetrahydrofuran (anhydrous, 10 mL) at 60° C. results in gelation after 1 hour. The gel was added to hexanes and allowed to sit overnight. A white solid was collected and dried under vacuum overnight (1.27 g, 83.6% yield). The resulting copolymer is not soluble in THF or chloroform, making characterization unfeasible. The difficulty in polymerization and purification of this copolymer hinders its potential use in commercial applications.

[0121] Comparative Example 3: The terpolymerization of (E)-4-methylstilbene (0.50 g, 2.6 mmol), (E)-2-methyl stilbene (0.50 g, 2.6 mmol) , and maleic anhydride (0.51 g, 5.2 mmol) in the presence of the radical initiator AIBN (0.015 g, 1 wt %) in tetrahydrofuran (anhydrous, 10 mL) at 60° C. results in gelation after 4 hours. The resulting gel was added to hexanes (300 mL) and allowed to sit overnight. A white precipitate was collected via filtration (0.41 g). A cloudy solution was observed when attempting to dissolve the white solid in THF, as well as chloroform.

[0122] Example 1: The copolymerization of the unsymmetrical (E)-2,4′-dimethylstilbene (1.00 g, 4.8 mmol) with maleic anhydride (0.47 g, 4.8 mmol) in the presence of the radical initiator dicumyl peroxide (0.015 g, 1 wt %) in chlorobenzene (anhydrous, 10 mL) at 110° C. does not result in gelation after 12 h. In addition to the lack of gelation, there is no apparent change in viscosity over the duration of the reaction. The reaction solution was added dropwise into stirring hexanes (300 mL). The white precipitate was collected via filtration and dissolved in THF (20 mL), the polymer solution was then added dropwise into stirring hexanes (300 mL). A white precipitate was collected via filtration and dried over vacuum overnight (1.14 g, 75.2% yield). Mn=27.5 KDa, Ð=1.7. The resulting copolymer readily dissolves in THF and chloroform, which results in fast purification and characterization by NMR and SEC.

[0123] Example 2: The copolymerization of (E)-4-methoxystilbene (1.50 g, 7.1 mmol) with maleic anhydride (0.70 g, 7.1 mmol) in the presence of the radical initiator AIBN (0.015 g, 1 wt %) in THF (anhydrous, 10 mL) at 110° C. does not result in gelation after 10 h. The reaction solution was added dropwise into stirring hexanes (300 mL). A white precipitate was collected via filtration and dissolved in THF (10 mL), the polymer solution was then added dropwise into stirring hexanes (300 mL). A white precipitate was collected via filtration and dried over vacuum overnight (1.37 g, 62.3% yield). Mn =67.5 KDa, Ð=2.5. The resulting copolymer readily dissolves in THF and chloroform, which results in fast purification and characterization by NMR and SEC.

[0124] Example 3: The copolymerization of (E)-4-methylstilbene (1.0 g, 5.1 mmol) with maleic anhydride (0.50 g, 5.1 mmol) in the presence of the radical initiator dicumyl peroxide (0.075 g, 5.44 mol %) in anisole (anhydrous, 10 mL) at 80 C does not result in gelation after 1 hour. The reaction solution was added dropwise into stirring ethanol (150 mL). A white precipitate was collected via filtration and dried in vacuo overnight (0.64 g, 42.33% yield). Mn=46 kDa, Ð=1.62.

[0125] Example 4: (E)-4-methylstilbene (1.0 g, 5.1 mmol), maleic anhydride (0.50 g, 5.1 mmol), radical initiator dicumyl peroxide (0.0054 g, 0.02 mmol), CTA1 (0.015 g, 0.04 mmol), and anisole (15 mL) were added to a 50-mL round-bottom flask equipped with a stir bar and sealed with a septum. The flask was placed under high vacuum for ˜20 min and then sparged with Ar for ˜15 min. The flask was placed in an oil bath at 120° C. for 24 h. No gelation over the course of the copolymerization was observed. The polymerization was quenched by removing the septum, the reaction mixture was added dropwise to stirring acetonitrile (150 mL). A yellow precipitate was collected via filtration and dried in vacuo at 80° C. overnight. (1.10 g, 73.0% yield). Mn=41 kDa. Ð=1.14.

[0126] Example 5: (E)-4-methylstilbene (0.70 g, 3.6 mmol), maleic anhydride (0.35 g, 3.6 mmol), radical initiator dibenzoyl peroxide (0.0070 g), CTA2 (0.066 g, 0.145 mmol), and anisole (10 mL) were added to a 50-mL round-bottom flask equipped with a stir bar and sealed with a septum. The flask was placed under high vacuum for ˜20 min and then sparged with Ar for —15 min. The flask was placed in an oil bath at 80° C. for 6 h. No gelation over the course of the copolymerization was observed. The polymerization was quenched by removing the septum, the opaque reaction mixture was added dropwise to stirring ethanol (100%, 150 mL). A yellow precipitate was collected via filtration and dried in vacuo at 80° C. overnight. (0.87 g, 82.28% yield). Mn=6700 Da. Ð=1.06.

[0127] Example 6: CTA2— benzyl 2-(((dodecylthio)carbonothioyl)thio)-2-methylpropanoate. 2-(((dodecylthio)carbonothioyl)thio)-2-methylpropanoic acid (4.00 g, 11.0 mmol) was dissolved in 55 mL of CH2Cl2 and added to a round-bottom flask equipped with a magnetic stir bar and rubber septum. 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide.Math.HCl (2.31 g, 12.1 mmol) and a catalytic amount of 4-(dimethylamino)pyridine (13.4 mg, 110 μmol) were added to the reaction and stirred at room temperature for 15 min. Next, benzyl bromide (1.25 mL, 1.30 g, 12.1 mmol) was added dropwise via syringe through the septum, and the reaction mixture was stirred for 17 hours at rt. Once reaction completion was confirmed via TLC in CH2Cl2, the reaction mixture was diluted with 30 mL of CH2Cl2, transferred to an Erlenmeyer flask, and acidified with 1 N HCl (2×100 mL). The organic layer was removed using a separatory funnel and further washed with water (2×100 mL) and brine (2×100 mL), dried over Na.sub.2SO.sub.4, then concentrated under reduced pressure to yield a dark yellow oil. The crude product was purified by silica gel column chromatography in 60:40 hexanes:CH2Cl2, and the product-containing fractions (R.sub.f˜0.67) were combined and concentrated via rotatory evaporation to yield a yellow oil (2.1 g, 42%). .sup.1H NMR (CDCl3, 400 MHz) was consistent with the expected structure.

[0128] Example 7: CTA3— benzyl 2-(((dodecylthio)carbonothioyl)thio)propanoate. 2-(((dodecylthio)carbonothioyl)thio)propanoic acid: 1-dodecanethiol (5.00 mL, 4.22g, 20.9 mmol) was added to a suspension of potassium triphosphate (8.86 g, 41.7 mmol) in acetone (30 mL) and stirred for 15 minutes at rt in a round-bottom flask equipped with a magnetic stir bar and rubber septum. The reaction mixture was cooled to 0° C. on an ice bath, and carbon disulfide (3.78 mL, 4.77 g, 62.6 mmol) was added dropwise via syringe through the septum to give an opaque yellow solution. After complete addition, the ice bath was removed, and the reaction mixture was allowed to warm to rt. The reaction mixture was then stirred for an additional 30 min. Next, 2-bromopropanoic acid (2.30 mL, 3.83 g, 25.0 mmol) was added dropwise via syringe through the septum, and the resulting yellow transparent solution was stirred for 18 hours at room temperature. Once reaction completion was confirmed via TLC in CH.sub.2Cl.sub.2 the reaction mixture was diluted with 50 mL of CH.sub.2Cl.sub.2, transferred to an Erlenmeyer flask, and acidified with 1 N HCl (2×100 mL). The organic layer was removed using a separatory funnel and further washed with water (2×100 mL) and brine (2×100 mL), dried over Na.sub.2SO.sub.4, then concentrated under reduced pressure to yield a yellow solid. The crude product was purified by silica gel column chromatography in 90:10 CH.sub.2Cl.sub.2: EtOAc, and the product-containing fractions (R.sub.f˜0.33) were combined and concentrated via rotatory evaporation to yield bright yellow crystals (5.76 g, 79%). .sup.1H NMR (CDCl.sub.3, 400 MHz) was consistent with the expected structure.

[0129] 2-(((dodecylthio)carbonothioyl)thio)propanoic acid (700 mg, 2.00 mmol) was dissolved in 10 mL of CH2Cl2 and added to a round-bottom flask equipped with a magnetic stir bar and rubber septum. 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide.Math.HCl (421 mg, 2.20 mmol) and a catalytic amount of 4-(dimethylamino)pyridine (2.44 mg, 20.0 μmol) were added to the reaction mixture and stirred at rt for 15 min. Next, benzyl bromide (228 μL, 238 mg, 2.20 mmol) was added dropwise via syringe through the septum, and the reaction mixture was stirred for 4 hours at rt. Once reaction completion was confirmed via TLC in CH.sub.2Cl.sub.2the reaction mixture was diluted with 10 mL of CH.sub.2Cl.sub.2, transferred to an Erlenmeyer flask, and acidified with 1 N HCl (2×25 mL). The organic layer was removed using a separatory funnel and further washed with water (2×25 mL) and brine (2×25 mL), dried over Na.sub.2SO.sub.4, then concentrated under reduced pressure to yield a yellow oil. The crude product was purified by silica gel column chromatography in 75:25 hexanes: CH.sub.2Cl.sub.2, and the product-containing fractions (R.sub.f˜0.70) were combined and concentrated via rotatory evaporation to yield a yellow oil (401 mg, 46%). .sup.1H NMR (CDCl.sub.3, 400 MHz) was consistent with the expected structure.

[0130] Example 8: Poly(4-cyano-4′-diethylaminostilbene-alt-maleic anhydride). 4-cyano-4′-diethylaminostilbene (1.41 g, 5.1 mmol), maleic anhydride (0.50 g, 5.1 mmol), AIBN (0.033 g, 4 mol %), and chlorobenzene (anhydrous, 15 mL) were added to a 50 mL round-bottom flask equipped with a stir bar and sealed with a septum. The flask was sparged with Ar for 15 min. The flask was placed in an oil bath at 65 C with stirring for 24 h. The polymerization was quenched by removing the septum. The reaction mixture was added dropwise to stirring diethyl ether. A yellow precipitate was collected via filtration and dried in vacuo overnight at 60 C. (1.37 g, 72.0% yield) Mn=7000 Da, Ð=1.32. Max excitation wavelength=340 nm. Emission at 340 nm=490 nm.

[0131] It will be apparent to those skilled in the art that various modifications and variations can be made in the present disclosure without departing from the scope or spirit of the disclosure. Other embodiments of the disclosure will be apparent to those skilled in the art from consideration of the specification and practice of the disclosure disclosed herein. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the disclosure being indicated by the following claims.