Monomers and polymers formed thereby

Monomers, polymers, or oligomers formed therefrom and methods of forming or utilizing monomers of formula I where R1 is a C1 to C4 alkyl; and X is —OH; —OM where M is lithium (Li), sodium (Na), or potassium (K), NH4+, R5NH3+, R52NH2+, R53NH+, R54N+ where R5 can independently be selected from alkyl, benzyl, and combinations thereof; —OR2 where R2 can be a C1 to C4 alkyl, 2-ethylhexyl, or a hydrocarbon moiety of bio-renewable alcohol or a hydrogenated derivative thereof; —NR3R4, —NR3—NR3R4, —NR3—OR4 where R3 and R4 can independently be H, a C1 to C4 alkyl, or combinations thereof.

SUMMARY

Disclosed are monomers of formula I

Disclosed are polymers formed from one or more monomers of formula I

where R1is a C1to C4alkyl; and X is —OH; —OM where M is lithium (Li), sodium (Na), or potassium (K), NH4+, R5NH3+, R52NH2+, R53NH+, R54N+where R5can independently be selected from C1-C4alkyl, benzyl, cetyl, and other alkyl moieties found in commonly utilized ammonium ions; —OR2where R2can be a C1to C4alkyl, 2-ethylhexyl, or a hydrocarbon moiety of bio-renewable alcohol or a hydrogenated derivative thereof; —NR3R4, —NR3—NR3R4, —NR3—OR4where R3and R4can independently be H, a C1to C4alkyl, or combinations thereof.

Also disclosed are methods that include the steps of combining anhydromevalonolactone with a metal-tert-alkoxide in a solvent to form a carboxylate salt of formula I

where R1is a C1to C4alkyl; and X is —OM where M is lithium (Li), sodium (Na), or potassium (K), NH4+, R5NH3+, R52NH2+, R53NH+, R54N+where R5can independently be selected from C1-C4alkyl, benzyl, cetyl, and other alkyl moieties found in commonly utilized ammonium ions; and treating the carboxylate salt of formula I with a mineral acid to form a mixture of the carboxylate salt of formula I and the acid thereof, wherein M is replaced with a hydrogen.

Also disclosed are monomers of formula II:

where R1is a C1to C4alkyl; and n is an integer from 0 to 6.

Also disclosed are monomers of formula III:

where R1is a C1to C4alkyl; and Y is a linker group.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

Unless otherwise specified, “a,” “an,” “the,” and “at least one” are used interchangeably and mean one or more than one. Reference to “a carboxylic acid compound”, for example, refers to a single carboxylic acid compound, multiple compounds of the same carboxylic acid compound, more than one specific carboxylic acid compound, multiple types of carboxylic acid compounds, mixtures of carboxylic acid compounds, or any combination thereof.

As used herein, “alkyl” is an unsubstituted or substituted saturated hydrocarbon chain radical having from 1 to about 12 carbon atoms; from 1 to about 10 carbon atoms; from about 1 to about 6 carbon atoms; or from about 1 to about 4 carbons. It should also be understood that an alkyl moiety can be a combination of two or more alkyl moieties. Illustrative, non-limiting examples of alkyl groups include, for example, methyl, ethyl, propyl, iso-propyl, and butyl. A C2to C4substituted or unsubstituted alkyl radical, for example refers to a C2to C4linear alkyl chain that may be unsubstituted or substituted. If the C2to C4linear alkyl chain is substituted with an alkyl radical, the carbon number of the alkyl radical increases as a function of the number of carbons in the alkyl substituent.

As used herein, “hydroxyl group” refers to a substituent group of formula —OH.

Referring to a compound herein refers to both enantiomeric versions of the compound. For example, referring to a compound refers to and includes both the Z- and E- isomers unless specifically stated otherwise.

In formulae herein, a squiggled bond (i.e.,), which is used to designate the attachment of a carbonyl group to an alkene double bond, is taken to mean that the geometry of that bond can be either of Z- or E-configuration in the compound in question or a mixture of both geometric isomers of that compound.

Disclosed herein are monomers and compounds produced from such monomers. Disclosed monomers can generally be described as a dienoate or derivatives thereof. In some embodiments, disclosed monomers can be formed using anhydromevalonolactone (compound 3 below) as a starting material. In some embodiments, anhydromevalonolactone can be subjected to eliminative opening under the action of potassium tert-butoxide, sodium ethoxide, or combinations thereof (which may proceed via the intermediate 5 and an E1cB mechanism) to produce compound 6 (shown below) which can then be subjected to Fischer esterification with an alcohol to produce desired monomers (referred to in the description of Scheme 2 as “isoprenecarboxylate esters”). This scheme is demonstrated below

In some embodiments, the monomers can be of formula I below, where the Z- and E-alkene isomers, as well as mixtures thereof are included:

In formula I, R1can be a substituted or unsubstituted C1to C4alkyl. In some embodiments, R1can be more specifically described as a methyl group (C1), an ethyl group (C2), a propyl group (C3) (e.g., an n-propyl group or an isopropyl group) or a butyl group (C4) (e.g., an n-butyl, sec-butyl, isobutyl, or tert-butyl). In formula I, X can be —OH; —OM where M can be lithium (Li), sodium (Na), potassium (K), NH4+, R5NH3+, R52NH2+, R53NH+, R54N+where R5can independently be selected from alkyl, benzyl (—CH2Phenyl), or combinations thereof; OR2where R2can be a substituted or unsubstituted C1to C4alkyl (e.g., a methyl group (C1), an ethyl group (C2), a propyl group (C3) (e.g., an n-propyl group or an isopropyl group) or a butyl group (C4) (e.g., an n-butyl, sec-butyl, isobutyl, or tert-butyl), 2-ethylhexyl, or a hydrocarbon moiety of bio-renewable alcohol such as geranyl, phytyl, cholesteryl, sitosteryl, ergosteryl, recinoleyl, etc. (or the hydrogenated derivatives thereof); —NR3R4, —NR3—NR3—R4, —NR3—OR4where R3and R4can independently be H, or a substituted or unsubstituted C1to C4alkyl (e.g., a methyl group (C1), an ethyl group (C2), a propyl group (C3) (e.g., an n-propyl group or an isopropyl group) or a butyl group (C4) (e.g., an n-butyl, sec-butyl, isobutyl, or tert-butyl), or combinations thereof; halide (e.g., chloride (Cl−), iodide (I), bromide (Br). In some embodiments, R5can be an alkyl moiety that is itself a combination of two or more alkyl moieties. In some embodiments R5can be an alkyl moiety found in commonly utilized ammonium ions. In some embodiments, R5can be a cetyl moiety.

In some embodiments starting materials for the monomers of formula I may be obtained via methods or processes described in United States Patent Publication Number US 2016/0068877, PCT Patent Application Publication Number WO 2015/161169, or both; the disclosures of which are incorporated herein by reference to the extent they do not conflict.

Also disclosed herein are polymers formed using one or more disclosed monomers, e.g., polymers, either homopolymers or copolymers, formed by polymerizing one or more compounds of formula I above. Polymers formed herein can be referred to as poly(isoprenecarboxylate) polymers, poly (isoprenecarboxylate) derivative polymers, or combinations thereof. Polymerization can be accomplished using any known methods, including for example radical polymerization, anionic polymerization, or combinations thereof. In some embodiments radical polymerization can be utilized. In some embodiments, reversible addition-fragmentation chain-transfer (RAFT) polymerization can be utilized. In some embodiments, nitroxide-mediated polymerization (NMP) can be utilized. Disclosed monomers can optionally be polymerized with a secondary monomer that is not a disclosed isoprenecarboxylate or derivative thereof monomer as well. In some embodiments, secondary monomers that can be polymerized (randomly, block, or combinations thereof) can include, for example petroleum-derived monomers including for example isoprene, butadiene and non-petroleum-derived monomers. In some embodiments, one or more disclosed monomers can be polymerized with one or more acid derivatives of one or more disclosed monomers. Such copolymerization can be utilized to form a hydrogel, for example.

Disclosed monomers can be utilized to form a hydrogel via inclusion in a copolymer. In some embodiments, a disclosed monomer(s) can form the majority (based on moles or weight, or both) monomer in a copolymer for use as a hydrogel. In some embodiments, disclosed monomer(s) can be polymerized and then cross linked to form a hydrogel. In some embodiments, disclosed monomer(s) can be polymerized and cross linked simultaneously to form a hydrogel. In some embodiments, the minority monomer can be difunctional or multifunctional crosslinking agent. In some embodiments, the minority monomer can be an acrylate monomer (or methacrylate monomer). In some embodiments, illustrative acrylate monomers can include bis-acrylates, tri-acrylates, tetra-acrylates (or methacrylates). Therefore, disclosed herein are copolymers formed from one or more monomers according to formula I above and one or more other monomers. In some embodiments, disclosed herein are copolymers formed from one or more monomers according to formula I above and itaconic acid or maleic acid or fumaric acid. In some embodiments, disclosed herein are copolymers formed from one or more monomers according to formula I above and one or more crosslinkable monomers. In some embodiments, disclosed herein are copolymers formed from one or more monomers according to formula I above and one or more acrylate or methacrylate containing monomers. In some embodiments, copolymers can be formed using at least 10 times the molar equivalent of the monomer of formula I as the crosslinkable monomer. In some embodiments, copolymers can be formed using at least 50 times the molar equivalent of the monomer of formula I as the crosslinkable monomer. In some embodiments, copolymers can be formed using at least 70 times the molar equivalent of the monomer of formula I as the crosslinkable monomer. In some embodiments, copolymers can be formed using at least 100 times the molar equivalent of the monomer of formula I as the crosslinkable monomer. In some embodiments, copolymers can be formed using at least 1000 times the molar equivalent of the monomer of formula I as the crosslinkable monomer. Disclosed hydrogels can be synthesized in, for example, a methanol/water solution or, even more advantageously, in water alone.

Also disclosed are monomers formed from monomers of formula I. In some embodiments, such monomers can be referred to as difunctional monomers. In some embodiments, such monomers can be of formula II below:

In formula II, R1can be a substituted or unsubstituted C1to C4alkyl. In some embodiments, R1can be more specifically described as a methyl group (C1), an ethyl group (C2), a propyl group (C3) (e.g., an n-propyl group or an isopropyl group) or a butyl group (C4) (e.g., an n-butyl, sec-butyl, isobutyl, or tert-butyl). In formula II, n can be an integer from 0 to 6.

Also disclosed are monomers formed from monomers of formula I and being of formula III below:

In formula III, R1can be a substituted or unsubstituted C1to C4alkyl. In some embodiments, le can be more specifically described as a methyl group (C1), an ethyl group (C2), a propyl group (C3) (e.g., an n-propyl group or an isopropyl group) or a butyl group (C4) (e.g., an n-butyl, sec-butyl, isobutyl, or tert-butyl). In formula III, Y is a linker group. In some embodiments, Y can be a linker group corresponding to a linker group commonly used in a bis-acrylate or bis-methacrylate crosslinking agent typically utilized in acrylate or methacrylate polymerization reactions. In some embodiments, Y can be a linker group comprising oligomeric ethylenoxy repeat units [Y=—(CH2CH2O)nCH2CH2, where n=1-200]. In some embodiments, Y can be the linker group derived from 1,2-, 1,3-, or 1,4-benzenedimethanol.

Polymers formed from disclosed monomers can be swelled by combining them with an aqueous solution optionally including counterion(s) (e.g., Na+, Li+, K+, or combinations thereof). Illustrative aqueous solutions can include deionized water (DI H2O) alone or aqueous solutions containing Na+, K30, Ca++, Mg++or combinations thereof. In some embodiments, 1% (weight/volume) aqueous solution of NaCl, KCl, or CaCl2can be utilized as a swelling solution.

As discussed above, disclosed polymers can function as or can have characteristics of a hydrogel. The particular properties of disclosed monomers or polymers can be affected based, at least in part, on the components making up the monomer or polymer formed thereby. For example, swelling properties of a polymer can be affected by the choice of counterion(s) in the monomer, the concentration of counterion(s) in a swelling solution, the identity of the crosslinking agent, the amount of the crosslinking agent, or combinations thereof.

In some embodiments, disclosed monomers can absorb or absorb and retain a greater amount of an aqueous solution such as a swelling solution than can a hydrogel made from acrylic acid when the two are prepared under substantially identical conditions. These monomers possess an increased distance between carboxylates. Due to this feature, the extent of “counterion condensation” (Manning, G. S.Q. Rev. Biophys.1978, 11, 179-246) may be reduced.

EXAMPLES

Esters were prepared and polymerized in various ways, including under RAFT and NMP conditions, to provide a series of high molecular weight polymers. The glass transition temperature and entanglement molecular weight of each was determined. The ester alkyl group in these polymers affected the Tgand Mein a very similar fashion as is known for simple poly(acrylates). This work established the feasibility of using glucose as a source of polymers with acrylate-like properties. Additionally, various alternative strategies are disclosed herein that capitalize on the ready availability of compounds 2-4 (in Scheme 1) in ways that might lead to additional novel monomers and/or polymers.

EXAMPLES

General Experimental Protocols

Materials: Anhydrous tetrahydrofuran (THF), dichloromethane (DCM), and diethyl ether were taken immediately prior to use from a column of activated alumina. Reported reaction temperatures are the temperature of the external heating or cooling bath.

NMR:1H and13C NMR spectra were recorded on a Bruker Avance 500 (500 MHz) or a Varian Inova 500 (500 MHz) spectrometers.1H NMR chemical shifts in CDCl3are referenced to TMS (δ 0.00 ppm). Non-first-order multiplets in1H NMR spectra have been identified as ‘nfom.’ The following format is used to report resonances: chemical shift in ppm [multiplicity, coupling constant(s) in Hz, integral, and assignment].1H NMR assignments are indicated by the substructural environment (e.g., CHaHb). Coupling constant analysis was led by methods we have described elsewhere.13C NMR chemical shifts for spectra recorded in CDCl3are referenced to the carbon resonance in CDCl3(δ 77.16).

ATR-FTIR: Fourier transform infrared (FTIR) spectra were recorded with a Bruker Alpha Platinum ATR-FTIR instrument (diamond single-bounce crystal). Typically 16 scans were acquired and a 4 s acquisition time was used.

Mass spectrometry of non-polymeric samples: MS measurements were made using electron impact ionization on an Agilent 5975 MSD at 70 eV GC-MS. The column stationary phase was an Agilent HP-5 with a 0.25 μm film thickness, 30 m long, ×0.32 mm i.d.

Size Exclusion Chromatography (SEC): SEC was conducted on a liquid chromatograph (Agilent 1100 series) fitted with a refractive index detector (HP1047A). Polymer samples were dissolved in CHC13 (1-2 mg·mL-1) and eluted through three successive Varian PLgel Mixed C columns (7.5 mm id; 25 cm 1) at 35° C. at a flow rate of 1 mL·min-1. Dispersity and mass-average molar mass of the samples were referenced to polystyrene standards.

Thermogravimetric Analysis (TGA): TGA was performed (TA Instruments Q500) at a heating rate of 10° C.·min-1 under an atmosphere of nitrogen. The sample size was 5-15 mg.

Differential Scanning Calorimetry (DSC): Differential scanning Calorimetry (TA Instruments Q-1000 DSC) was performed on samples hermetically sealed in aluminum pans. Each sample was heated to 250° C., cooled to −60° C., and reheated to 250° C. Glass transition temperatures were taken as the inflection point and are reported as measured on the second (or third) heating cycle.

Linear Viscosity (Rheology) Measurements: A 0.50 g sample of solid polymer was placed onto the bottom rheometer plate (2.5 cm d) held at the desired reference temperature (70° C. above the Tg). The top plate was manually lowered under a steady rate sweep at a frequency of 0.1/s for approximately 2 full rotations to prepare the sample for the measurements. A dynamic strain sweep was taken at this temperature to ensure linearity within the sample. The dynamic linear viscoelastic measurements were carried out within the linear viscoelastic regime at temperatures in the range from 10 to 125° C. The dynamic measurements were conducted in the range of 0.1-100 rad/s at a strain of 1%. A gap of approximately 1.0 mm was used to minimize edge effects. The rheological measurements were carried out under an atmosphere of nitrogen to minimize oxidative events of the polymer samples during testing. Entanglement molecular weights were approximated using the equation

Me=45⁢ρ⁢⁢RTGN.
The plateau moduli were calculated using the minimum of tan delta vs G′.
Preparation of Monomers

A series of four esters of isoprenecarboxylic acid (6-H) that differed in the size of the ester alkyl moiety were prepared herein as shown in Scheme 1. The parent acid was made by an eliminative opening of anhydromevalonolactone (3), a commodity efficiently available in large quantities from glucose (Xiong, M.; Schneiderman, D. K.; Bates, F. S.; Hillmyer, M. A.; Zhang, K. Proc. Natl. Acad. Sci. 2014, 111, 8357-8362).

Specific Illustrative Syntheses

To a 50 mL two-neck round bottom flask equipped with a stir bar was added potassium metal (1.08 equiv, 0.487 g, 12.5 mmol), followed by dry, warm tert-butanol (10.1 equiv, 11.2 mL, 117 mmol). A bubbler was affixed to allow for the escape of hydrogen gas and the mixture was stirred under a slight positive pressure of nitrogen. After one hour at room temperature, the mixture was heated to 80° C. and stirred for 21 h until complete dissolution of the solid potassium had occurred. This solution of potassium tert-butoxide (1.06 M) was added rapidly to a stirring solution of 4-methyl-5,6-dihydro-2H-pyran-2-one (3, 1 equiv, 1.3 g, 11.6 mmol) in diethyl ether (8 mL). Immediate appearance of a precipitate was observed. The solid was collected by filtration (1.77 g). Analysis by1H NMR spectroscopy (D2O) indicated the solid to contain potassium (Z)-3-methylpenta-2,4-dienoate (6-K), potassium formate (a few percent), and potassium (Z)-5-hydroxy-3-methylpent-2-enoate. The purity of 6-K was judged to be ca. 90%.

Alternatively, commercially available potassium tert-butoxide was used to synthesize 6-K. Anhydromevalanolactone (3, 1 equiv, 6.06 g, 54.1 mmol) was dissolved in diethyl ether (15 mL) and added to a cooled (0° C.) solution of tert-butoxide (6.67 g, 59.6 mmol) in tert-butanol (20 mL) and diethyl ether (15 mL) in a 250 mL round bottom flask. A precipitate formed nearly immediately. After being stirred for approximately 10 minutes, the slurry was filtered, and the solid was rinsed thoroughly with diethyl ether. The crude mixture (8.70 g) was recovered as a tan solid. Similar purity was observed as described above. This material was used without further purification. (The yield of acid 6-H, obtained by the acidification procedure described below, was 5.34 g or 88%.)

The salt 6-K (35 g) was dissolved in water (200 mL) and diethyl ether (100 mL) was added. Aqueous hydrochloric acid was added to this mixture until the pH of the aqueous portion fell to ca. 3). The aqueous portion was extracted with additional diethyl ether. The combined organic layers were dried over MgSO4, filtered, and concentrated to provide acid 6-H (20 g, 77% yield).

The material could be molecularly distilled in a sublimation apparatus held at ca. 210° C. at ca. 1 torr, or alternatively it could be recrystallized from a mixture of ethanol and water Acid (6-H) was found to be somewhat sensitive to light and was stored in the dark.

To an 80 mL screw cap topped culture tube equipped with a stir bar was added methanol (28 equiv, 25 mL, 0.6 mol) and thionyl chloride (25 mol %, 0.4 mL, 5.51 mmol). After five minutes, (Z)-3-methylpenta-2,4-dienoic acid (1 equiv, 2.44 g, 21.8 mmol) was added followed by phenothiazine (7 mol %, 0.03 g, 0.15 mmol). The tube was capped and stirred at 76° C. for 18 h and allowed to cool. The contents were added to a saturated solution of sodium bicarbonate (100 mL) followed by extraction with diethyl ether (100 mL×3). The organic layers were combined, dried (MgSO4), and concentrated in vacuo.1H NMR analysis of an aliquot of this crude reaction product indicated that all of the acid had been consumed. This material was distilled at ambient temperature under reduced pressure (1.5 torr) into a flask cooled in a −78° C. bath to afford methyl (Z)-3-methylpenta-2,4-dienoate (6-Me, 2.18 g, 17.3 mmol, 79% yield). Visual inspection of the reaction mixture when no phenothiazine was added led us to conclude that polymerization had occurred.

To an 80 mL screw cap topped culture tube equipped with a stir bar was added ethanol (19 equiv, 50 mL, 0.85 mol) and thionyl chloride (24 mol %, 0.8 mL, 11 mmol). After five minutes, (Z)-3-methylpenta-2,4-dienoic acid (1 equiv, 4.7 g, 43 mmol) was added followed by phenothiazine (3 mol %, 0.03 g, 0.15 mmol). The tube was capped and stirred at 86° C. for 18 h and allowed to cool. The contents were added to a saturated solution of sodium bicarbonate (100 mL) and then extracted with diethyl ether (100 mL×3). The organic layers were combined, dried (MgSO4), and concentrated in vacuo. This material was distilled at 35° C. under reduced pressure (1.5 torr) into a flask cooled in a −78° C. bath to afford ethyl (Z)-3-methylpenta-2,4-dienoate (6-Et, 3.52 g, 25.2 mmol, 59% yield, 91:9 mixture of Z:E isomers).

Thionyl chloride (0.13 equiv, 1 mL, 13.8 mmol) was added in dropwise fashion to a 200 mL heavy-walled glass pressure tube containing n-butanol (10 equiv, 100 mL, 1.08 mol). The tube was capped and the mixture was stirred for five minutes to allow generation of anhydrous HCl. (Z)-3-Methylpenta-2,4-dienoic acid (1 equiv, 4.7 g, 42 mmol) was added in one portion. The pressure tube was recapped and heated to 100° C. After 18 h the mixture was allowed to cool, and the butanol solution was partitioned between saturated potassium carbonate (100 mL) and methylene chloride. The aqueous layer was extracted 3× with dichloromethane, and the organic layers were combined, dried over MgSO4, and concentrated. Phenothiazine (0.1 g) was added to minimize polymerization and this material was distilled under reduced pressure to afford butyl (Z)-3-methylpenta-2,4-dienoate (6-nBu, 4.8 g, 34.3 mmol, 81.7% yield, 86:14 mixture of Z:E isomers (1H NMR analysis)).

(Z)-3-Methylpenta-2,4-dienoic acid (3.00 g, 26.7 mmol) was added to an 80 mL screw cap culture tube equipped with a stir bar. The solution was cooled to −78° C. and isobutylene (15 equivalents, 38 mL, 400 mmol), which had been pre-condensed in a graduated cylinder, was added. Concentrated sulfuric acid (0.2 equivalents, 280 μL, 5.34 mmol) was added, the culture tube was capped, and the mixture was stirred for 7 h at 35° C. No starting 6-H remained (1H NMR analysis). The culture tube was cooled to −78° C., opened, and approximately 20 mL of diethyl ether and 20 mL of saturated sodium bicarbonate (gas evolution) were added. The mixture was allowed to warm to ambient temperature to allow for slow evaporation of excess isobutylene over ca. 1 h while stirring. The remaining contents were diluted into ca. 100 mL of diethyl ether, washed with saturated sodium bicarbonate and brine, dried (MgSO4), and concentrated to leave a yellow oil (4.73 g). Phenothiazine (0.1 g) was added and this crude material was distilled under reduced pressure (0.7 torr) to afford tert-butyl (Z)-3-methylpenta-2,4-dienoate (6-tBu, 3.54 g, 21.7 mmol, 78.9% yield).

Isoprenecarboxamides 6-AM can be synthesized from the isoprenecarboxylic acid (6-H). These can be made by initial conversion to the isoprenecarboxylic acid chloride (6-Cl) and then reacted with either of ammonia or a primary or secondary amine.

Synthesis of Isoprenecarboxamides

As one example, (Z)-3-methylpenta-2,4-dienoic acid (6-H, 1.0 equiv, 1.50 g, 13.3 mmol), THF (20 mL), and DMF (50 mL) were added to a 6-dram vial fitted with a stir bar. Oxalyl chloride (1.1 equiv, 1.30 mL, 14.7 mmol) was added dropwise over the course of 10 minutes. Once bubbling had ceased, an aliquot was taken and the reaction progress was evaluated via1H NMR analysis. The formation of acid chloride 6-Cl was judged to be complete. At this point, Hunig's base (1 equiv, 2.30 mL, 13.3 mL) was added followed by cold, liquefied dimethylamine (5.6 equiv, ca. 5.0 mL, 74 mmol) at 0° C. Stirring slowed almost immediately as a precipitate appeared, and THF (10 mL) was added to allow for continued stirring for 20 minutes. Excess solvent and reagents were removed in vacuo and the remaining mixture was taken up in DCM, washed with 0.1 M HCl, brine, dried (MgSO4), and concentrated to give 1.67 g of (Z)-N,N,3-trimethylpenta-2,4-dienamide (6-AMc) as a yellow oil. The liquid was distilled twice (77° C., 0.1 mmHg) to give the material (960 mg, 6.7 mmol, 50% yield) as a clear liquid.

Polymerization

The compounds synthesized above were then polymerized using various methods.

First azobisisobutyronitrile (AIBN) was used to initiate a polymerization of methyl isoprenecarboxylate (6-Me) (Scheme 3) to provide poly(methyl isoprenecarboxylate) (PMIC). This reaction was examined both in the bulk and in methanol at varying initial monomer concentrations. This demonstrated that 6-Me behaves in a similar fashion to other conjugated dienoates (FIG. 1).1H and13C NMR analysis of the PMIC suggested that the polymerization occurs via competing 1,4- and 1,2-addition modes in a ratio of ca. 1.5:1. Additionally, the broad nature of nearly all resonances were indicative of the likely formation of multiple diastereomeric relationships among the new stereogenic alkene (E/Z) and sp3carbon atoms (R/S) that arise from the addition of each monomer.

Procedure for AIBN Initiated Free Radical Polymerization of (Z)-3-methylpenta-2,4-dienoate (6-Me)

A stock solution of methyl (Z)-3-methylpenta-2,4-dienoate (6-Me, 0.21 g, 1.66 mmol) and (E)-2,2′-(diazene-1,2-diyl)bis(2-methylpropanenitrile) (AIBN, 4.1 mg, 0.025 mmol) was prepared. After the full dissolution of AIBN in the diene, the stock solution was dispensed into a series of 2 mL ampules (51 mg each). To each of these was added one of four solvents (benzene, acetonitrile, toluene, and methanol; 0.12 mL). The ampule was degassed through a series of three freeze-pump-thaw cycles and sealed under vacuum with a torch. The ampule was heated at 65° C. for 48 h. The ampule was allowed to cool to ambient temperature and a portion of the contents was analyzed by1H NMR spectroscopy to determine the conversion. The remainder of the reaction mixture was freed of solvent in vacuo and then analyzed by SEC to determine the molecular weight and dispersity.

A competition experiment was also carried out in which the two diene monomers 6-Me and ethyl sorbate (ethyl hexa-2,4-dienoate) were copolymerized to partial (ca. 50%) conversion under AIBN initiation in order to gain some insight about the relative reactivity of the two. Although overlap of resonances from each of the unreactive monomers and the copolymer product made it difficult to obtain precise quantitative assessment, it was concluded that the 6-Me was consumed about 4 times faster than the ethyl sorbate. This is consistent with an expected easier approach of any propagating radical to the unsubstituted methylene carbon (C5) of the monomer 6-Me compared to attack at C5 of ethyl sorbate.

Procedure for competition experiment for the copolymerization of ethyl sorbate and (Z)-3-methylpenta-2,4-dienoate (6-Me) (Scheme 4)

To a 2 mL ampule was added (E)-2,2′-(diazene-1,2-diyl)bis(2-methylpropanenitrile) (AIBN, 1 equiv, 2 mg, 0.01 mmol) followed by methyl (Z)-3-methylpenta-2,4-dienoate (6-Me, ca. 80 mg, 0.6 mmol) and ethyl sorbate (ca. 90 mg, 0.6 mmol). After full dissolution of the AIBN at ambient temperature, an aliquot of the mixture was taken that showed (1H NMR) a 44:56 molar mixture of 6-Me:ethyl sorbate. The ampule was degassed through a series of three freeze-pump-thaw cycles and sealed under vacuum with a torch. The ampule was heated at 65° C. for 29 h. The ampule was allowed to cool to ambient temperature and the contents were analyzed by1H NMR spectroscopy to determine the conversion, amounts of 6-Me and ethyl sorbate remaining, and the composition of the copolymer.

Ethyl sorbate is somewhat less reactive than 6-Me toward radical polymerization. This may reflect the higher degree of substitution and increased steric bulk of the alkenes in the former compared to the latter.

Reversible addition-fragmentation chain-transfer (RAFT) polymerization of the esters 6-R (FIG. 3A) was also investigated. When 6-Me (1 equiv) was polymerized in the presence of AIBN (8×10−5equiv) and the trithiocarbonate 12 (DDMAT (2-{[(dodecylthio)carbonothioyl]thio}-2-methylpropanoic acid), 1×10−3equiv) as the RAFT agent, the resulting PMIC showed an Mnof 150 kg·mol−1and a dispersity of 1.5 (SEC vs. PS) (FIGS. 3B and 3C). The Tgof the sample was 34° C. and its entanglement molecular weight (Me=4ρRT/5Gn°) was 17 kg·mol−1(FIG. 4). The RAFT polymerization of 6-Me again appeared to be living (FIGS. 3B and 3C). As has been reported with, for example, methyl methacrylate, this RAFT polymerization also proceeded in the absence of a radical initiator (Stickler, M.; Meyerhoff, G. Makromol. Chem. 1978, 179, 2729-2745. Paulus, R. M.; Becer, C. R.; Hoogenboom, R.; Schubert, U. S. Aust. J. Chem. 2009, 62, 254-259). It is also worth noting that neither of these controlled polymerization methods altered the ratio of 1,4- vs. 1,2-addition modes of polymerization (i.e., the ratio remained ca. 1.5:1).

With the goal of establishing the effect of the ester alkyl moiety on Tgand Me, high molecular weight polymer samples were also prepared from the series of esters 6-Et, 6-nBu, and 6-tBu. Samples of each of PEIC, PnBIC, and PtBIC having Mn>100 kg·mol−1were prepared using AIBN and 12. The Tgs and Mes of these poly(isoprenecarboxylates) are given in Table 1. The Tgs decrease as the ester alkyl moiety grows in size until the t-butyl analogue is reached, in which case there is a substantial increase in the Tg. This is quite analogous to the trend seen for simple poly(acrylate) esters (Table 1). Similarly, the Mes for the poly(isoprenecarboxylates) parallel those for the analogous poly(acrylates). The former tend to be higher than the latter for most of the same ester alkyl groups, perhaps reflecting the contribution from the larger side chain moieties arising from the 1,2-mode of polymerization of the isoprenecarboxylate monomers 6.

Procedures for RAFT Polymerization

AIBN (0.08 equiv, 0.16 mg, 1.0 μmol) was added as a stock solution in DCM (10 mg·mL−1) to a 10 mL Schlenk flask. The DCM was removed under reduced pressure and 2-{[(dodecylthio)carbonothioyl]thio}-2-methylpropanoic acid (DDMAT, 12, 1.0 equiv, 4.3 mg, 12 μmol) and methyl (Z)-3-methylpenta-2,4-dienoate (6-Me, 1000 equiv, 1.50 g, 11.9 mmol) were added. The headspace was degassed through several freeze-pump-thaw cycles, under static vacuum, until bubbling no longer was observed during thawing. Nitrogen was then admitted and the flask was heated in an oil bath held at 95° C. Aliquots were periodically withdrawn under nitrogen flow.1H NMR analysis of each crude aliquot relied, principally, on integration of the following resonances: 7.81-H4 in the starting 6-Me; 6.40-H4 in a small amount of the E-isomer of 6-Me (E-6-Me) that appears during the polymerization; and 4.9-6.0, the superposition of the single alkene proton arising from both the 1,4- and 1,2-modes of addition in the PMIC polymer as well as protons H2, HSE, and H5Zin both 6-Me and E-6-Me.1H NMR analysis of the crude aliquots indicated >94% conversion of the monomer after 5 days. The flask was allowed to cool to ambient temperature, the residue was dissolved in dichloromethane, and the polymer was precipitated by addition to swirled methanol held at 0° C. The resulting slurry was cooled (−20° C.), centrifuged, decanted, and rendered free of solvent under vacuum overnight at 70° C. to provide 1.26 g of PMIC (84% yield). This product was judged to arise from a 42:58 ratio of 1,2- and 1,4-modes of polymerization (cf. “y” vs. “x”, respectively, in the structure of PMIC) across the conjugated diene based on integration of1H NMR resonances from 5.83-5.37 ppm (from moieties arising from 1,2-addition) and 5.37-4.92 ppm (from moieties arising from 1,4-addition). A nearly identical ratio for the 1,2- and 1,4-modes was seen in the relative intensities of the13C NMR resonances for the conjugated (167.0-165.5 ppm) vs. unconjugated (174.2-173.0 ppm) carbonyl carbons.

The thermal degradation of the polymer shown inFIG. 8.

AIBN (0.08 equiv, 0.14 mg, 0.9 μmol) was added as a stock solution in DCM (10 mg·mL−1) to a 10 mL Schlenk flask. The DCM was removed under reduced pressure and 2-{[(dodecylthio)carbonothioyl]thio}-2-methylpropanoic acid (DDMAT, 12, 1.0 equiv, 3.9 mg, 10.7 μmol) and ethyl (Z)-3-methylpenta-2,4-dienoate (6-Et, 1000 equiv, 1.50 g, 10.7 mmol) were added. The headspace was degassed through several freeze-pump-thaw cycles, under static vacuum, until bubbling no longer was observed during thawing. Nitrogen was then admitted and the flask was heated in an oil bath held at 95° C. Aliquots were periodically withdrawn under nitrogen flow. As with the examples above,1H NMR analysis of the crude aliquots indicated >98% conversion of the monomer after 4 days. The flask was allowed to cool to ambient temperature, the residue was dissolved in dichloromethane, and the polymer was precipitated by addition to swirled methanol held at 0° C. The resulting slurry was cooled in (−20° C.), centrifuged, decanted, and rendered free of solvent under vacuum overnight at 70° C. to provide 1.18 g of PEIC (79% yield).

This product was also judged to arise from a 42:58 ratio of 1,2- and 1,4-modes of polymerization (cf. “y” vs. “x”, respectively) across the conjugated diene based on integration of1H NMR resonances from 5.85-5.38 ppm (from moieties arising from 1,2-addition) and 5.38-4.97 ppm (from moieties arising from 1,4-addition). A nearly identical ratio for the 1,2- and 1,4-modes was seen in the relative intensities of the13C NMR resonances for the conjugated (166.8-165.0 ppm) vs. unconjugated (173.0-172.5 ppm) carbonyl carbons.

The thermal degradation of the polymer shown inFIG. 8.

AIBN (0.08 equiv, 0.14 mg, 0.7 μmol) was added as a stock solution in DCM (10 mg·mL−1) to a 10 mL Schlenk flask. The DCM was removed under reduced pressure and 2-{[(dodecylthio)carbonothioyl]thio}-2-methylpropanoic acid (DDMAT, 12, 1.0 equiv, 10.8 mg, 29.6 μmol) and tert-butyl (Z)-3-methylpenta-2,4-dienoate (6-nBu, 300 equiv, 1.50 g, 8.93 mmol) were added. The headspace was degassed through several freeze-pump-thaw cycles, under static vacuum, until bubbling no longer was observed during thawing. Nitrogen was then admitted and the flask, which was heated in an oil bath held at 115° C. Aliquots were periodically withdrawn under nitrogen flow. As with the examples above,1H NMR analysis of the crude aliquots indicated >90% conversion of the monomer after 7 days, and the Mn, Mw, andwere analyzed (Mn=69,000 g mol−1, Mw=90,000 g mol−1,=1.3). To demonstrate the livingness of this polymerization, more 6-nBu (320 eq, 1.6 g, 9.5 mmol) was added and the same freeze-pump-thaw cycles were performed. After introduction of nitrogen into the headspace, the Schlenk flask was placed into an oil bath at 95° C.1HNMR analysis of the crude aliquots indicated >90% conversion of the monomer after 6 days. The flask was allowed to cool to ambient temperature and the residue was dissolved in dichloromethane and the polymer was precipitated by addition to swirled methanol held at 0° C. The resulting slurry was cooled (−20° C.), centrifuged, decanted, and rendered free of solvent under vacuum overnight at 70° C. to provide 1.96 g of PnBIC (63% yield). This sample was judged to be a 41:59 mixture of 1,2:1,4 addition products based on integration of1H NMR peaks from 5.90-5.40 ppm (1,2 addition) and 5.40-4.95 ppm (1,4 addition). A nearly identical ratio was seen for the 1,2- and 1,4-modes in the relative intensities of the13C NMR resonances for the conjugated (166.8-165.1 ppm) vs. unconjugated (173.7-172.5 ppm) carbonyl carbons.

The thermal degradation of the polymer shown inFIG. 8.

AIBN (0.08 equiv, 0.12 mg, 0.7 μmol) was added as a stock solution in DCM (10 mg·mL−1) to a 2 mL Schlenk flask. The DCM was removed under reduced pressure and DDMAT (12, 1.0 equiv, 3.2 mg, 8.9 μmol) and tert-butyl (Z)-3-methylpenta-2,4-dienoate (6-tBu, 1000 equiv, 1.50 g, 8.93 mmol) were added. The headspace was degassed through several freeze-pump-thaw cycles, under static vacuum, until bubbling no longer was observed during thawing. Nitrogen was then admitted and the flask, which was heated in an oil bath held at 115° C. Aliquots were periodically withdrawn under nitrogen flow. As with the examples above,1H NMR analysis of the crude aliquots indicated >90% conversion of the monomer after 4 days. The flask was allowed to cool to ambient temperature, the residue was dissolved in dichloromethane, and the polymer was precipitated by addition to swirled methanol held at 0° C. The resulting slurry was cooled (−20° C.), centrifuged, decanted, and rendered free of solvent under vacuum overnight at 70° C. to provide 1.22 g of PtBIC (81% yield).

This sample was judged to be a 40:60 mixture of 1,2:1,4-addition products based on integration of1H NMR peaks from 5.79-5.37 ppm (1,2 addition) and 5.37-4.94 ppm (1,4 addition). A nearly identical ratio was seen for the 1,2- and 1,4-modes in the relative intensities of the13C NMR resonances for the conjugated (166.6-164.8 ppm) vs. unconjugated (173.4-172.0 ppm) carbonyl carbons.

Characterization of the Polymers

Preparation of Poly(isoprenecarboxylic acid)

Preparation of Poly(isoprenecarboxamides)

RAFT polymerization of each of the prepared isoprenecarboxamides was carried out in the same manner as described earlier for the isoprenecarboxylic esters to produce the poly(isoprenecarboxamides).

Preparation of Hydrogels and Poly(isoprenecarboxamides)

Hydrogels can be prepared according to the reaction seen inFIG. 18. Specifically, cross-linked versions of [poly(isoprenecarboxylic acid)] were synthesized by AIBN initiated polymerization of 6-H in the presence of the bis-ester derived via 6-H and 1,4-butanediol. The starting acid was pretreated with varying amounts of sodium hydroxide (from 0.1 to 0.9 equiv of the carboxylic acid 6-H) and this mixture polymerized directly to provide polymers as a pale yellow, clear gel. This was suspended in water to remove non-crosslinked polymers. Acetone was added several times to leach away the water by decantation. The residue was dried at 70° C. under vacuum for a day and ground to a fine white powder. This material was shown to have hydrogel properties—the ability to absorb large (on a wt:wt basis) amounts of water. The powdered samples could be swelled to hold about 205-335 times their mass of water. Analogous lithium or potassium salts were also prepared and shown to behave as hydrogels as well.

Alternatively, hydrogels can be prepared by crosslinking using a bis-methacrylate, which is less expensive, albeit not as environmentally advantageous, than an alternative, bis-isoprenecarboxylate-containing crosslinking agent.

2,2′-Azobis(2-methylpropionitrile) (AIBN, 0.01 equiv, 6.4 mg, 0.04 mmol), (Z)-3-methylpenta-2,4-dienoic acid (1.0 equiv, 448 mg, 4.00 mmol), and MeOH (400 μL) were added to a 1-dram vial. Sodium hydroxide was added via a 7.9 M solution (0.9 equiv, 455 μL, 3.60 mmol) followed by additional water (155 μL) to neutralize 90% of the carboxylic acid groups to sodium carboxylates. The crosslinking agent, butane-1,4-diyl (2Z,2′Z)-bis(3-methylpenta-2,4-dienoate) (0.01 equiv, 11.2 mg, 0.04 mmol) was added in MeOH (200 μL). The headspace was evacuated via freeze-pump-thaw cycles until bubbling no longer persisted upon thawing. Nitrogen gas was admitted, and the vial was sealed with a Teflon-fitted cap. The vial was placed into a sand bath held at 65° C. for 24 hours. The newly formed gel was then transferred to a 6-dram vial and soluble impurities were removed through first introducing water (ca. 8 mL) to slightly-swell the polymer. This material was washed repeatedly with acetone, during which the polymer contracted in volume significantly as the water was leached from the sample. This material was then placed under hi-vacuum for 48 hours at 70° C. and ground to a fine white powder using a mortar and pestle.

Hydrogel Preparation

A portion (25-50 mg) of the above crosslinked powder was allowed to swell in water for 24 h and excess water was pipetted off and additionally removed by gently wiping with a moist paper towel.FIG. 18shows a photograph of the hydrogel after swelling. The masses of water retained by hydrogels based on polymers of varying proportions of acid:carboxylate, after being immersed in either pure water or various salt solutions, are shown in Tables 2a-c andFIG. 38Additionally, these sodiated hydrogels swell more in the presence of water at higher ionizations (NaOH equivalents) than do acrylic acid-based hydrogels synthesized under identical conditions, presumably due to the increased distance between carboxylates (FIG. 38).

One step preparation of hydrogel monomer feed.

Single step preparation of mixtures of acid 6-H and its carboxylate salt 6-M (M=Li, Na, K) that are suitable as a monomer feed for direct use in hydrogel polymerization procedure described above could also be prepared. Namely, the lactone 3 could be opened, for example, with one molar equivalent of Metal-tert-butoxide (Metal=lithium, sodium, or potassium) in tert-butanol or THF as solvent to produce the carboxylate salt 6-M. This mixture could be treated with a mineral acid like aqueous HCl, H2SO4, or HNO3, for example, using molar ratios varying from 0.1 to 0.9 relative to the salt 6-M. The solvent composition could be adjusted, as needed, to precipitate the mixture of 6-H/6-M, which could be used in the same fashion as described above.

Thus, embodiments of monomers and polymers formed thereby are disclosed. The implementations described above and other implementations are within the scope of the following claims. One skilled in the art will appreciate that the present disclosure can be practiced with embodiments other than those disclosed. The disclosed embodiments are presented for purposes of illustration and not limitation.