Process for producing catechol-styrene copolymer

Abstract

Poly(catechol-styrene) (PCS) is a new material with a variety of industrial and biomedical applications. For example, PCS can act as an adhesive that functions in wet or underwater environments, making it useful for biomedical applications. The present disclosure provides a method for forming a poly(catechol-styrene) polymer. The method includes polymerizing 3,4-diacetoxystyrene and styrene via emulsion polymerization to form a poly(3,4-diacetoxystyrene-co-styrene) polymer. This polymer has acetate groups deprotected from the alcohol to form the poly(catechol-styrene) polymer. The poly(catechol-styrene) polymer has improved strength at higher molecular weights.

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of U.S. Provisional Application No. 63 / 481,245, filed January 24, 2023, which is incorporated herein by reference in its entirety. [Background technology]

[0002] Poly(catechol-styrene) (PCS) is an emerging material with a variety of industrial and biomedical applications. For example, PCS can act as an adhesive, functioning in wet or underwater environments, making it useful for a variety of applications. The challenge is to produce PCS in an economically viable process. To incorporate the catechol moiety into PCS, the catechol hydroxyl groups must be protected before polymerization. The free hydroxyl of catechol acts as a radical scavenger and can have adverse effects on polymerization, such as crosslinking and unexpected molecular weight.

[0003] Most known polystyrene processes (and styrenic copolymers) use RAFT or solvent-based anionic polymerization methods. The challenge with these types of polymerizations is that they are slow and do not lead to complete conversion. Large-scale polystyrene processes (and styrenic copolymers) are carried out using solvent polymerization, which typically results in only 90% monomer conversion. For most commercially available styrenic copolymers, this level of monomer conversion is not an issue. At the end of such processes, multistage extraction / extrusion is used to raise the polymer above its melting point, volatilize all impurities, and extrude the pure polymer. The problem with applying these processes to the production of PCS is that PCS is sensitive to heat and oxygen (especially both). As a result, it is important for commercially viable polymerization methods for PCS production to achieve monomer conversion rates approaching 100%. Summary of the Invention

[0004] The present disclosure provides a method for forming a poly(catechol-styrene) polymer. The method includes polymerizing 3,4-diacetoxystyrene and styrene via emulsion polymerization to form a poly(3,4-diacetoxystyrene-co-styrene) polymer. The polymer has acetate groups that are deprotected from an alcohol to form the poly(catechol-styrene) polymer. The poly(catechol-styrene) polymer has improved strength at higher molecular weights. [Brief explanation of the drawings]

[0005] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments and, together with the general description given above and the detailed description of the embodiments given below, serve to explain the principles of the disclosure.

[0006] [Figure 1] 1 is a graph of the molecular weight of the resulting polymer based on the amount of initiator used during polymerization. [Figure 2] 1 is a graph of the molecular weight of the resulting polymer based on the amount of chain transfer agent used during the polymerization of Example 3. [Figure 3] 1 is a table comparing the dry adhesive strength of poly(catechol-styrene) polymers made by processes using diacetoxy and methoxy protecting groups, along with their molecular weights. Example 6. [Figure 4] 1 is a table comparing the wet adhesive strength of poly(catechol-styrene) polymers made by processes using diacetoxy and methoxy protecting groups, along with their molecular weights. Example 7. DETAILED DESCRIPTION OF THE INVENTION

[0007] The present disclosure provides a scalable process that can be used to produce poly(catechol-styrene) using relatively inexpensive raw materials. Caffeic acid is naturally present in almost all plant species and is a readily available starting material. Caffeic acid can undergo one-pot decarboxylation and hydroxyl protection to form catechol-containing monomers. The use of an acid-labile protecting group, such as acetate, allows the catechol moiety to be liberated after polymerization under inexpensive and mild conditions.

[0008] In some aspects, the present disclosure relates to a method of forming a poly(catechol-styrene) polymer, comprising: (i) polymerizing 3,4-diacetoxystyrene and styrene to form a poly(3,4-diacetoxystyrene-co-styrene) polymer; (ii) deprotecting the acetate groups of the resulting poly(3,4-diacetoxystyrene-co-styrene) polymer to form a poly(catechol-styrene) polymer; Includes:

[0009] In some aspects, the present disclosure relates to a method of forming a poly(catechol-styrene) polymer, comprising: (i) polymerizing 3,4-diacetoxystyrene and styrene by emulsion polymerization to form poly(3,4-diacetoxystyrene-co-styrene) polymer; (ii) deprotecting the acetate groups of the resulting poly(3,4-diacetoxystyrene-co-styrene) polymer to form a poly(catechol-styrene) polymer.

[0010] In some embodiments, 3,4-diacetoxystyrene (DAS) monomer is copolymerized with styrene monomer by emulsion polymerization techniques as shown in Scheme I. Scheme I [ka]

[0011] In some embodiments of emulsion polymerization, the monomers polymerized are 3,4-diacetoxystyrene (DAS) monomer and styrene. Methods for making DAS are known in the art.

[0012] The ratio of 3,4-diacetoxystyrene (DAS) monomer to styrene monomer affects the relative amounts of these moieties in the resulting poly(3,4-diacetoxystyrene-co-styrene) polymer and the final poly(catechol-styrene) polymer. In some embodiments, the polymerization reaction further includes a monomer having a fatty acid chain, such that the polymerization reaction produces a modified PCS.

[0013] In some embodiments, the weight ratio of styrene monomer to DAS monomer used in the polymerization reaction is from about 0.1 to about 5.0, e.g., about 0.1, about 0.11, about 0.12, about 0.13, about 0.14, about 0.15, about 0.16, about 0.17, about 0.18, about 0.19, about 0.20, about 0.21, about 0.22, about 0.23, about 0.24, about 0.25, about 0.26, about 0.27, about 0.28, about 0.29, about 0.30, about 0.31, about 0.32, about 0.33 , about 0.34, about 0.35, about 0.36, about 0.37, about 0.38, about 0.39, about 0.40, about 0.41, about 0.42, about 0.43, about 0.44, about 0.45, about 0.46, about 0.47, about 0.48, about 0.49, about 0.50, about 0.51, about 0.52, about 0.53, about 0.54, about 0.55, about 0.56, about 0.57, about 0.58, about 0.59, about 0.60, about 0.61, about 0.62, about 0.63, about 0.64, about 0.65, about 0.66, about 0.67 7, about 0.68, about 0.69, about 0.70, about 0.71, about 0.72, about 0.73, about 0.74, about 0.75, about 0.76, about 0.77, about 0.78, about 0.79, about 0.80, about 0.81, about 0.82, about 0.83, about 0.84, about 0.85, about 0.86, about 0.87, about 0.88, about 0.89, about 0.90, about 0.91, about 0.92, about 0.93, about 0.94, about 0.95, about 0.96, about 0.97, about 0.98, about 0.99, about 1.0, about 1.1. about 1.2, about 1.3, about 1.4, about 1.5, about 1.6, about 1.7, about 1.8, about 1.9, about 2.0, about 2.1, about 2.2, about 2.3, about 2.4, about 2.5, about 2.6, about 2.7, about 2.8, about 2.9, about 3.0, about 3.1, about 3.2, about 3.3, about 3.4, about 3.5, about 3.6, about 3.7, about 3.8, about 3.9, about 4.0, about 4.1, about 4.2, about 4.3, about 4.4, about 4.5, about 4.6, about 4.7, about 4.8, about 4.9, or about 5.0.

[0014] In some embodiments, the weight ratio of styrene monomer to DAS monomer used in the polymerization reaction is from about 1.1 to about 1.9, e.g., about 1.10, about 1.11, about 1.12, about 1.13, about 1.14, about 1.15, about 1.16, about 1.17, about 1.18, about 1.19, about 1.20, about 1.21, about 1.22, about 1.23, about 1.24, about 1.25, about 1.26, about 1.27, about 1.28, about 1.29, about 1.30, about 1.31, about 1.32, about 1.33, about 1.34, about 1.35, about 1.36, about 1.37, about 1.38, about 1.39, about 1.40, about 1.41, about 1.42, about 1.43, about 1.44, about 1.45 , about 1.46, about 1.47, about 1.48, about 1.49, about 1.50, about 1.51, about 1.52, about 1.53, about 1.54, about 1.55, about 1.56, about 1.57, about 1.58, about 1.59, about 1.60, about 1.61, about 1.62, about 1.63, about 1.64, about 1.65, about 1.66, about 1.67, about 1.68 , about 1.69, about 1.70, about 1.71, about 1.72, about 1.73, about 1.74, about 1.75, about 1.76, about 1.77, about 1.78, about 1.79, about 1.80, about 1.81, about 1.82, about 1.83, about 1.84, about 1.85, about 1.86, about 1.87, about 1.88, about 1.89, or about 1.90.

[0015] In other embodiments, the weight ratio of styrene monomer to DAS monomer used in the polymerization reaction is from about 1.4 to about 1.5, e.g., about 1.40, about 1.41, about 1.42, about 1.43, about 1.44, about 1.45, about 1.46, about 1.47, about 1.48, about 1.49, or about 1.50.

[0016] In some embodiments of emulsion polymerization, the monomers are mixed with a surfactant, an initiator, and a chain transfer agent.

[0017] In some embodiments of emulsion polymerization, the monomers are mixed with a surfactant, such as an anionic surfactant, a cationic surfactant, a nonionic surfactant, or any combination thereof. In some embodiments of emulsion polymerization, the surfactant is sodium lauryl sulfate (i.e., sodium dodecyl sulfate), other sulfates, carboxylic acids (e.g., fatty acids), sulfonic acid esters, and phosphorus compounds. Other examples include alkyl alcohols, such as cetyl alcohol.

[0018] In some embodiments, the ratio of surfactant to total monomer, expressed as a percentage, is from about 0.2% to about 6.0%, e.g., about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.6%, about 1.7%, about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, About 2.7%, about 2.8%, about 2.9%, about 3.0%, about 3.1%, about 3.2%, about 3.3%, about 3.4%, about 3.5%, about 3.6%, about 3.7%, about 3.8%, about 3.9%, about 4.0%, about 4.1%, about 4.2%, about 4.3%, about 4.4%, about 4.5%, about 4.6%, about 4.7%, about 4.8%, about 4.9%, about 5.0%, about 5.1%, about 5.2%, about 5.3%, about 5.4%, about 5.5%, about 5.6%, about 5.7%, about 5.8%, about 5.9%, or about 6.0%. As used herein, percentages are calculated as (weight of surfactant) / (weight of DAS + weight of styrene) * 100.

[0019] In some embodiments, the ratio of surfactant to total monomer, expressed as a percentage, is from about 0.8% to about 3.0%, e.g., about 0.8%, about 0.9%, about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.6%, about 1.7%, about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, or about 3.0%. In some embodiments, the ratio of sodium lauryl sulfate to total monomers, expressed as a percentage, is about 1.2% to about 1.4%, e.g., about 1.20%, about 1.21%, about 1.22%, about 1.23%, about 1.24%, about 1.25%, about 1.26%, about 1.27%, about 1.28%, about 1.29%, about 1.30%, about 1.31%, about 1.32%, about 1.33%, about 1.34%, about 1.35%, about 1.36%, about 1.37%, about 1.38%, about 1.39%, or about 1.40%. As used herein, percentages are calculated as (weight of surfactant) / (weight of DAS+weight of styrene)*100.

[0020] In some embodiments, the surfactant is sodium lauryl sulfate (ie, sodium dodecyl sulfate).

[0021] In some embodiments, the ratio of sodium lauryl sulfate to total monomers, expressed as a percentage, is from about 0.2% to about 6.0%, e.g., about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.6%, about 1.7%, about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, about 3.0%, about 3.1%, about 3.2%, about 3.3%, about 3.4%, about 3.5%, about 3.6%, about 3.7%, about 3.8%, about 3.9%, about 4.0%, about 4.1%, about 4.2%, about 4.3%, about 4.4%, about 4.5%, about 4.6%, about 4.7%, about 4.8%, about 4.9%, about 5.0%, about 5.1%, about 5.2%, about 5.3%, about 5.4%, about 5.5%, about 5.6%, about 5.7%, about 5.8%, about 5.9%, about 6.0%, about 6.1%, about 6.1%, about 6.2%, about 6.3%, about 6.4%, about 6.5%, about 6.6%, about 6.7%, about 6.8%, about 6.9%, about 7.0%, about 7.1%, about 7.1%, about 7.2%, about 7.3%, about 7.4%, about 7.5%, about 7.6%, about 7.7%, about 7%, approximately 1.8%, approximately 1.9%, approximately 2.0%, approximately 2.1%, approximately 2.2%, approximately 2.3%, approximately 2.4%, approximately 2.5%, approximately 2.6%, approximately 2.7%, approximately 2.8%, approximately 2.9%, approximately 3.0%, approximately 3.1%, approximately 3.2%, approximately 3.3%, approximately 3.4%, approximately 3.5%, approximately 3.6%, approximately 3.7%, approximately 3.8%, approximately 3.9%, approximately 4.0%, approximately 4.1%, approximately 4.2%, approximately 4.3%, approximately 4.4%, about 4.5%, about 4.6%, about 4.7%, about 4.8%, about 4.9%, about 5.0%, about 5.1%, about 5.2%, about 5.3%, about 5.4%, about 5.5%, about 5.6%, about 5.7%, about 5.8%, about 5.9%, or about 6.0%.

[0022] In some embodiments, the ratio of sodium lauryl sulfate to total monomers, expressed as a percentage, is about 0.8% to about 3.0%, e.g., about 0.8%, about 0.9%, about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.6%, about 1.7%, about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, or about 3.0%. In some embodiments, the ratio of sodium lauryl sulfate to total monomers, expressed as a percentage, is about 1.2% to about 1.4%, e.g., about 1.20%, about 1.21%, about 1.22%, about 1.23%, about 1.24%, about 1.25%, about 1.26%, about 1.27%, about 1.28%, about 1.29%, about 1.30%, about 1.31%, about 1.32%, about 1.33%, about 1.34%, about 1.35%, about 1.36%, about 1.37%, about 1.38%, about 1.39%, or about 1.40%. As used herein, percentages are calculated as (weight of SLS) / (weight of DAS+weight of styrene)*100.

[0023] In another embodiment, the surfactant is cetyl alcohol.

[0024] In some embodiments, the ratio of cetyl alcohol to total monomers, expressed as a percentage, is from about 0.5% to about 10.0%, e.g., about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.6%, about 1.7%, about 1.8%, about 1.9%, about 2.0%, about 2.1%, approximately 2.2%, approximately 2.3%, approximately 2.4%, approximately 2.5%, approximately 2.6%, approximately 2.7%, approximately 2.8%, approximately 2.9%, approximately 3.0%, approximately 3.1%, approximately 3.2%, approximately 3.3%, approximately 3.4%, approximately 3.5%, approximately 3.6%, approximately 3.7%, approximately 3.8%, approximately 3.9%, approximately 4.0%, approximately 4.1%, approximately 4.2%, approximately 4.3%, approximately 4.4%, approximately 4.5%, approximately 4.6%, approximately 4.7%, approximately 4.8%, approximately 4.9%, approximately 5.0%, approximately 5.1%, approximately 5.2%, approximately 5.3%, approximately 5.4%, approximately 5.5%, approximately 5.6%, approximately 5.7%, approximately 5.8%, approximately 5.9%, approximately 6.0%, approximately 6.1%, approximately 6.2%, approximately 6.3%, approximately 6.4%, approximately 6.5%, approximately 6.6%, approximately 6.7%, approximately 6.8%, approximately 6.9%, approximately 7.0%, approximately 7.1%, approximately 7.2%, approximately 7.3%, approximately 7.4%, approximately 7.5%, about 7.6%, about 7.7%, about 7.8%, about 7.9%, about 8.0%, about 8.1%, about 8.2%, about 8.3%, about 8.4%, about 8.5%, about 8.6%, about 8.7%, about 8.8%, about 8.9%, about 9.0%, about 9.1%, about 9.2%, about 9.3%, about 9.4%, about 9.5%, about 9.6%, about 9.7%, about 9.8%, about 9.9%, or about 10.0%.

[0025] In some embodiments, the ratio of cetyl alcohol to total monomers, expressed as a percentage, is from about 2.0% to about 7.0%, e.g., about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, about 3.0%, about 3.1%, about 3.2%, about 3.3%, about 3.4%, about 3.5%, about 3.6%, about 3.7%, about 3.8%, about 3.9%, about 4.0%, or about 5.0%. %, about 4.1%, about 4.2%, about 4.3%, about 4.4%, about 4.5%, about 4.6%, about 4.7%, about 4.8%, about 4.9%, about 5.0%, about 5.1%, about 5.2%, about 5.3%, about 5.4%, about 5.5%, about 5.6%, about 5.7%, about 5.8%, about 5.9%, about 6.0%, about 6.1%, about 6.2%, about 6.3%, about 6.4%, about 6.5%, about 6.6%, about 6.7%, about 6.8%, about 6.9%, or about 7.0%. In other embodiments, the ratio of cetyl alcohol to total monomers, expressed as a percentage, is from about 2.50% to about 3.40%, e.g., 2.50%, 2.51%, 2.52%, 2.53%, 2.54%, 2.55%, 2.56%, 2.57%, 2.58%, 2.59%, 2.60%, 2.61%, 2.62%, 2.63%, 2.64%, 2.65%, 2.66%, 2.67%, 2.68%, 2.69%, 2.70%, 2.71%, 2.72%, 2.73%, 2.74%, 2.75%, 2.76%, 2.77%, 2.78%, 2.79%, 2.80%, 2.81%, 2.82%, 2.83%, 2.84%, 2.85%, 2.86%, 2.87%, 2.88%, 2.89%, 2.90 %, 2.91%, 2.92%, 2.93%, 2.94%, 2.95%, 2.96%, 2.97%, 2.98%, 2.99%, 3.00%, 3.01%, 3.02%, 3.03%, 3.04%, 3.05%, 3.06%, 3.07%, 3.08%, 3.09%, 3.10%, 3.11%, 3.12%, 3.13%, 3.14%, 3.15%, 3. 16%, 3.17%, 3.18%, 3.19%, 3.20%, 3.21%, 3.22%, 3.23%, 3.24%, 3.25%, 3.26%, 3.27%, 3.28%, 3.29%, 3.30%, 3.31%, 3.32%, 3.33%, 3.34%, 3.35%, 3.36%, 3.37%, 3.38%, 3.39%, or 3.40%.As used herein, percentages are calculated as (weight of cetyl alcohol) / (weight of DAS+weight of styrene)*100.

[0026] In yet other embodiments, the surfactant is a mixture of sodium lauryl sulfate and cetyl alcohol. In some embodiments, the weight ratio of cetyl alcohol to sodium lauryl sulfate is about 2.0 to about 4.0, e.g., about 2.0, about 2.1, about 2.2, about 2.3, about 2.4, about 2.5, about 2.6, about 2.7, about 2.8, about 2.9, about 3.0, about 3.1, about 3.2, about 3.3, about 3.4, about 3.5, about 3.6, about 3.7, about 3.8, about 3.9, or about 4.0.

[0027] In other embodiments, the weight ratio of cetyl alcohol to sodium lauryl sulfate is from about 2.30 to about 2.80, e.g., about 2.30, about 2.31, about 2.32, about 2.33, about 2.34, about 2.35, about 2.36, about 2.37, about 2.38, about 2.39, about 2.40, about 2.41, about 2.42, about 2.43, about 2.44, about 2.45, about 2.46, about 2.47, about 2.48, about 2.49, about 2.50, about 2.51, about 2.52, about 2.53, about 2.54, about 2.55, about 2.56, about 2.57, about 2.58, about 2.59, about 300, about 301, about 302, about 303, about 304, about 305, about 306, about 307, about 308, about 309, about 310, about 311, about 312, about 313, about 314, about 315, about 316, about 317, about 318, about 319, about 320, about 321, about 322, about 323, about 324, about 325, about 326, about 327, about 328, about 329, about 330, about 331, about 332, about 333, about 334, about 335, about 336, about 337, about 338, about 339, about 340, about 341, about 342, about 34 0.51, about 2.52, about 2.53, about 2.54, about 2.55, about 2.56, about 2.57, about 2.58, about 2.59, about 2.60, about 2.61, about 2.62, about 2.63, about 2.64, about 2.65, about 2.66, about 2.67, about 2.68, about 2.69, about 2.70, about 2.71, about 2.72, about 2.73, about 2.74, about 2.75, about 2.76, about 2.77, about 2.78, about 2.79 or about 2.80.

[0028] In some embodiments of emulsion polymerization, the polymerization mixture includes an initiator, such as persulfates (e.g., sodium persulfate, potassium persulfate, ammonium persulfate, other persulfates), benzoyl peroxide, t-butyl hydroperoxide, and other water-soluble free radical initiators.

[0029] In some embodiments, the ratio of initiator to total monomer, expressed as a percentage, is from about 0.1% to about 3.0%, e.g., about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.6%, about 1.7%, about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, or about 3.0%. As used herein, percentages are calculated as (weight of initiator) / (weight of DAS+weight of styrene)*100.

[0030] In some embodiments, the ratio of initiator to total monomer, expressed as a percentage, is about 1.0% to about 3.0%, e.g., about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.6%, about 1.7%, about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, or about 3.0%. As used herein, percentages are calculated as (weight of initiator) / (weight of DAS+weight of styrene)*100.

[0031] In some embodiments, the ratio of initiator to total monomer, expressed as a percentage, is about 1.2% to about 1.4%, such as about 1.20%, about 1.21%, about 1.22%, about 1.23%, about 1.24%, about 1.25%, about 1.26%, about 1.27%, about 1.28%, about 1.29%, about 1.30%, about 1.31%, about 1.32%, about 1.33%, about 1.34%, about 1.35%, about 1.36%, about 1.37%, about 1.38%, about 1.39%, or about 1.40%. As used herein, percentages are calculated as (weight of initiator) / (weight of DAS + weight of styrene) * 100.

[0032] In some embodiments, the initiator is a water-soluble free radical initiator.

[0033] In some embodiments, the initiator is potassium persulfate.

[0034] In some embodiments, the initiator is sodium persulfate.

[0035] In some embodiments, the initiator is ammonium persulfate.

[0036] In some embodiments, the initiator is benzoyl peroxide.

[0037] In some embodiments, the initiator is t-butyl hydroperoxide.

[0038] In some embodiments, the ratio of potassium persulfate to total monomers, expressed as a percentage, is from about 0.1% to about 3.0%, e.g., about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.6%, about 1.7%, about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, or about 3.0%. As used herein, percentages are calculated as (weight of potassium persulfate) / (weight of DAS+weight of styrene)*100.

[0039] In some embodiments, the ratio of potassium persulfate to total monomers, expressed as a percentage, is about 1.0% to about 3.0%, e.g., about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.6%, about 1.7%, about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, or about 3.0%. As used herein, percentages are calculated as (weight of potassium persulfate) / (weight of DAS+weight of styrene)*100.

[0040] In some embodiments, the ratio of potassium persulfate to total monomers, expressed as a percentage, is about 1.2% to about 1.4%, e.g., about 1.20%, about 1.21%, about 1.22%, about 1.23%, about 1.24%, about 1.25%, about 1.26%, about 1.27%, about 1.28%, about 1.29%, about 1.30%, about 1.31%, about 1.32%, about 1.33%, about 1.34%, about 1.35%, about 1.36%, about 1.37%, about 1.38%, about 1.39%, or about 1.40%. As used herein, percentages are calculated as (weight of potassium persulfate) / (weight of DAS+weight of styrene)*100.

[0041] In some embodiments of emulsion polymerization, the polymerization mixture includes a chain transfer agent, such as dodecylthiol (also known as dodecyl mercaptan or n-dodecanethiol), carbon tetrachloride, or a halocarbon. The amount of chain transfer agent used varies the molecular weight of the polymer.

[0042] In some embodiments, the ratio of chain transfer agent to total monomer, expressed as a percentage, is from about 0.05% to about 10%, e.g., about 0.05%, about 0.06%, about 0.07%, about 0.08%, about 0.09%, about 0.10%, about 0.11%, about 0.12%, about 0.13%, about 0.14%, about 0.15%, about 0.16%, about 0.17%, about 0.18%, about 0.19%, about 0.20%, about 0.21%, about 0.22%, about 0.23%, about 0.24%, about 0.25%, about 0.26%, about 0.27%, about 0.28%, about 0.29%, about 0.30%, about 0.31%. ,approx. 0.32%,approx. 0.33%,approx. 0.34%,approx. 0.35%,approx. 0.36%,approx. 0.37%,approx. 0.38%,approx. 0.39%,approx. 0.40%,approx. 0.41%,approx. 0.42%,approx. 0.43%,approx. 0.4%,approx. 0.45%,approx. 0.46%,approx. 0.47%,approx. 0.48%,approx. 0.49% ,approx. 0.50%,approx. 0.51%,approx. 0.52%,approx. 0.53%,approx. 0.54%,approx. 0.55%,approx. 0.56%,approx. 0.57%,approx. 0.58%,approx. 0.59%,approx. 0.60%,approx. 0.61%,approx. 0.62%,approx. 0.63%,approx. 0.64%,approx. 0.65%,approx. 0.66%,approx. 0.67 %,approximately 0.68%,approximately 0.69%,approximately 0.70%,approximately 0.71%,approximately 0.72%,approximately 0.73%,approximately 0.74%,approximately 0.75%,approximately 0.76%,approximately 0.77%,approximately 0.78%,approximately 0.79%,approximately 0.80%,approximately 0.81%,approximately 0.82%,approximately 0.83%,approximately 0.84%,approximately 0. 85%, approx. 0.86%, approx. 0.87%, approx. 0.88%, approx. 0.89%, approx. 0.90%, approx. 0.91%, approx. 0.92%, approx. 0.93%, approx. 0.94%, approx. 0.95%, approx. 0.96%, approx. 0.97%, approx. 0.98%, approx. 0.99%, approx. 1.0%, approx. 1.1%, approx. 1.2%, approx. 1.3% ,approximately 1.4%,approximately 1.5%,approximately 1.6%,approximately 1.7%,approximately 1.8%,approximately 1.9%,approximately 2.0%,approximately 2.1%,approximately 2.2%,approximately 2.3%,approximately 2.4%,approximately 2.5%,approximately 2.6%,approximately 2.7%,approximately 2.8%,approximately 2.9%,approximately 3.0%,approximately 3.1%,approximately 3.2%,approximately 3.3%,approximately 3.4 %, about 3.5%, about 3.6%, about 3.7%, about 3.8%, about 3.9%, about 4.0%, about 4.1%, about 4.2%, about 4.3%, about 4.4%, about 4.5%, about 4.6%, about 4.7%, about 4.8%, about 4.9%, about 5.0%, about 5.1%, about 5.2%, about 5.3%, about 5.4%, about 5.5%, approx. 5.6%, approx. 5.7%, approx. 5.8%, approx. 5.9%, approx. 6.0%, approx. 6.1%, approx. 6.2%, approx. 6.3%, approx. 6.4%, approx. 6.5%, approx. 6.6%, approx. 6.7%, approx. 6.8%, approx. 6.9%, approx. 7.0%, approx. 7.1%, approx. 7.2%, approx. 7.3%, approx. 7.4%, approx. 7.5%, approx. 7.6%, approx. 7.7%, approx. 7.8% , about 7.9%, about 8.0%, about 8.1%, about 8.2%, about 8.3%, about 8.4%, about 8.5%, about 8.6%, about 8.7%, about 8.8%, about 8.9%, about 9.0%, about 9.1%, about 9.2%, about 9.3%, about 9.4%, about 9.5%, about 9.6%, about 9.7%, about 9.8%, about 9.9%, or about 10.0%. As used herein, percentages are calculated as (weight of chain transfer agent) / (weight of DAS+weight of styrene)*100.

[0043] In some embodiments, the ratio of chain transfer agent to total monomer, expressed as a percentage, is from about 0.1% to about 0.8%, e.g., about 0.10%, about 0.11%, about 0.12%, about 0.13%, about 0.14%, about 0.15%, about 0.16%, about 0.17%, about 0.18%, about 0.19%, about 0.20%, about 0.21%, about 0.22%, about 0.23%. ,approx. 0.24%,approx. 0.25%,approx. 0.26%,approx. 0.27%,approx. 0.28%,approx. 0.29%,approx. 0.30%,approx. 0.31%,approx. 0.32%,approx. 0.33%,approx. 0.34%,approx. 0.35%,approx. 0.36%,approx. 0.37%,approx. 0.38%,approx. 0.39%,approx. 0.40%,approx. 0.41%,approx. 0.42%,approx. 0.43%,approx. 0.45%,approx. 0.46%. 6%, approx. 0.47%, approx. 0.48%, approx. 0.49%, approx. 0.50%, approx. 0.51%, approx. 0.52%, approx. 0.53%, approx. 0.54%, approx. 0.55%, approx. 0.56%, approx. 0.57%, approx. 0.58%, approx. 0.59%, approx. 0.60%, approx. 0.61%, approx. 0.62%, approx. 0.63%, approx. 0.64%, approx. 0.65%, approx. 0.66%, approx. 0.67%, approx. 0.68%, approx. 0.69%, about 0.70%, about 0.71%, about 0.72%, about 0.73%, about 0.74%, about 0.75%, about 0.76%, about 0.77%, about 0.78%, about 0.79%, about 0.80%, about 0.81%, about 0.82%, about 0.83%, about 0.84%, about 0.85%, about 0.86%, about 0.87%, about 0.88%, about 0.89%, or about 0.90%. As used herein, percentages are calculated as (weight of chain transfer agent) / (weight of DAS+weight of styrene)*100.

[0044] In some embodiments, the chain transfer agent is dodecylthiol.

[0045] In some embodiments, the chain transfer agent is carbon tetrachloride.

[0046] In some embodiments, the chain transfer agent is a halocarbon.

[0047] In some embodiments, the ratio of dodecyl thiol to total monomers, expressed as a percentage, is from about 0.05% to about 10%, e.g., about 0.05%, about 0.06%, about 0.07%, about 0.08%, about 0.09%, about 0.10%, about 0.11%, about 0.12%, about 0.13%, about 0.14%, about 0.15%, about 0.16%, about 0.17%, about 0.18%, about 0.19%, about 0.20%, about 0.21%, about 0.22%, about 0.23%, about 0.24%, about 0.25%, about 0.26%, about 0.27%, about 0.28%, about 0.29%, about 0.30%, about 0.31%, about 0.32%, about 0.33%, about 0.34%, about 0.35%, about 0.36%, about 0.37%, about 0.38%, about 0.39%, about 10.40%, about 10.41%, about 10.42%, about 10.43%, about 10.44%, about 10.45%, about 10.46%, about 10.47%, about 10.48%, about 10.49%, about 11.50%, about 11.51%, about 11.52%, about 11.53%, about 11.54%, about 11.55%, about 11.56%, about 11.57%, about 11.58%, about 11.59%, about 12.60%, about 12.61%, about 12.62%, about 12.63%, about 12.64%, about 12.65%, about 12.66%, about 12.67 1%, approx. 0.32%, approx. 0.33%, approx. 0.34%, approx. 0.35%, approx. 0.36%, approx. 0.37%, approx. 0.38%, approx. 0.39%, approx. 0.40%, approx. 0.41%, approx. 0.42%, approx. 0.43%, approx. 0.45%, approx. 0.46%, approx. 0.47%, approx. 0.48%, approx. 0.4 9%, approx. 0.50%, approx. 0.51%, approx. 0.52%, approx. 0.53%, approx. 0.54%, approx. 0.55%, approx. 0.56%, approx. 0.57%, approx. 0.58%, approx. 0.59%, approx. 0.60%, approx. 0.61%, approx. 0.62%, approx. 0.63%, approx. 0.64%, approx. 0.65%, approx. 0.66%, approx. 67%, approx. 0.68%, approx. 0.69%, approx. 0.70%, approx. 0.71%, approx. 0.72%, approx. 0.73%, approx. 0.74%, approx. 0.75%, approx. 0.76%, approx. 0.77%, approx. 0.78%, approx. 0.79%, approx. 0.80%, approx. 0.81%, approx. 0.82%, approx. 0.83%, approx. 0.84%, approx. 0 0.85%, approx. 0.86%, approx. 0.87%, approx. 0.88%, approx. 0.89%, approx. 0.90%, approx. 0.91%, approx. 0.92%, approx. 0.93%, approx. 0.94%, approx. 0.95%, approx. 0.96%, approx. 0.97%, approx. 0.98%, approx. 0.99%, approx. 1.0%, approx. 1.1%, approx. 1.2%, approx. 1.3 %, about 1.4%, about 1.5%, about 1.6%, about 1.7%, about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, about 3.0%, about 3.1%, about 3.2%, about 3.3%, about 3. 4%, approximately 3.5%, approximately 3.6%, approximately 3.7%, approximately 3.8%, approximately 3.9%, approximately 4.0%, approximately 4.1%, approximately 4.2%, approximately 4.3%, approximately 4.4%, approximately 4.5%, approximately 4.6%, approximately 4.7%, approximately 4.8%, approximately 4.9%, approximately 5.0%, approximately 5.1%, approximately 5.2%, approximately 5.3%, approximately 5.4%, approximately 5.5%, approx. 5.6%, approx. 5.7%, approx. 5.8%, approx. 5.9%, approx. 6.0%, approx. 6.1%, approx. 6.2%, approx. 6.3%, approx. 6.4%, approx. 6.5%, approx. 6.6%, approx. 6.7%, approx. 6.8%, approx. 6.9%, approx. 7.0%, approx. 7.1%, approx. 7.2%, approx. 7.3%, approx. 7.4%, approx. 7.5%, approx. 7.6%, approx. 7.7%, approx. 7.8% , about 7.9%, about 8.0%, about 8.1%, about 8.2%, about 8.3%, about 8.4%, about 8.5%, about 8.6%, about 8.7%, about 8.8%, about 8.9%, about 9.0%, about 9.1%, about 9.2%, about 9.3%, about 9.4%, about 9.5%, about 9.6%, about 9.7%, about 9.8%, about 9.9%, or about 10.0%. As used herein, percentages are calculated as (weight of dodecyl thiol) / (weight of DAS+weight of styrene)*100.

[0048] In some embodiments, the ratio of dodecyl thiol to total monomers, expressed as a percentage, is from about 0.1% to about 0.8%, e.g., about 0.10%, about 0.11%, about 0.12%, about 0.13%, about 0.14%, about 0.15%, about 0.16%, about 0.17%, about 0.18%, about 0.19%, about 0.20%, about 0.21%, about 0.22%, about 0.23%, about 0.24%, about 0.25%, about 0.26%, about 0.27%, about 0.28%, about 0.29%, about 0.30%, about 0.31%, about 0.32%, about 0.33%, about 0.34%, about 0.35%, about 0.36%, about 0.37%, about 0.38%, about 0.39%, about 10.40%, about 10.41%, about 10.42%, about 10.43%, about 10.44%, about 10.45%, about 10.46%, about 10.47%, about 10.48%, about 10.49%, about 11.50%, about 11.51%, about 11.52%, about 11.53%, about 11.54%, about 11.55%, about 11.56%, about 11.57%, about 11.58%, about 11.59%, about 12.60%, about 12.61%, about 12.62%, about 12.63%, about 12.64%, about 12.65%, about 12.66%, about 12.67%, about 12.68%, about 12.69%, about 13.70%, about 13.71%, about 3%, approximately 0.24%, approximately 0.25%, approximately 0.26%, approximately 0.27%, approximately 0.28%, approximately 0.29%, approximately 0.30%, approximately 0.31%, approximately 0.32%, approximately 0.33%, approximately 0.34%, approximately 0.35%, approximately 0.36%, approximately 0.37%, approximately 0.38%, approximately 0.39%, approximately 0.40%, approximately 0.41%, approximately 0.42%, approximately 0.43%, approximately 0.45%, approximately 0. 46%, approx. 0.47%, approx. 0.48%, approx. 0.49%, approx. 0.50%, approx. 0.51%, approx. 0.52%, approx. 0.53%, approx. 0.54%, approx. 0.55%, approx. 0.56%, approx. 0.57%, approx. 0.58%, approx. 0.59%, approx. 0.60%, approx. 0.61%, approx. 0.62%, approx. 0.63%, approx. 0.64%, approx. 0.65%, approx. 0.66%, approx. 0.67%, approx. 0.68%, approx. 0.69%, about 0.70%, about 0.71%, about 0.72%, about 0.73%, about 0.74%, about 0.75%, about 0.76%, about 0.77%, about 0.78%, about 0.79%, about 0.80%, about 0.81%, about 0.82%, about 0.83%, about 0.84%, about 0.85%, about 0.86%, about 0.87%, about 0.88%, about 0.89%, or about 0.90%. As used herein, percentages are calculated as (weight of dodecylthiol) / (weight of DAS + weight of styrene) * 100.

[0049] In some embodiments, the polymerization reaction also includes a buffer, such as sodium bicarbonate.

[0050] In some embodiments, the polymerization reaction is an emulsion polymerization. Thus, the solvent for emulsion polymerization includes an aqueous solvent, such as water. The emulsion is formed using a surfactant and, optionally, a salt. An initiator, such as potassium persulfate, initiates the polymerization reaction. In some embodiments, the reaction is carried out at an elevated temperature, such as from 65° C. to the boiling point of the solvent.

[0051] In some embodiments, 3,4-diacetoxystyrene (DAS) is copolymerized with styrene by emulsion polymerization. Styrene and 3,4-diacetoxystyrene (DAS) are blended together in a desired ratio with a chain transfer agent to obtain a monomer blend. In some embodiments, the molecular weight of the polymer can be controlled by varying the amount of chain transfer agent.

[0052] The monomer blend is then added to a stirred aqueous solution of surfactant, chain initiator, and buffer at elevated temperature in an inert atmosphere to obtain an emulsion polymerization reaction mixture.

[0053] In some embodiments, the amount of water used in the emulsion polymerization as a function of the total monomer used in the reaction is from about 190 to about 320 grams of total monomer per liter of water, e.g., about 190, 195, 200, 205, 210, 215, 220, 225, 230, 235, 240, 245, 250, 255, 260, 265, 270, 275, 280, 285, 290, 295, 300, 305, 310, 315, or 320 grams of total monomer per liter of water.

[0054] In some embodiments, the elevated temperature is from about 40°C to about 100°C, e.g., about 40°C, about 41°C, about 42°C, about 43°C, about 44°C, about 45°C, about 46°C, about 47°C, about 48°C, about 49°C, about 50°C, about 51°C, about 52°C, about 53°C, about 54°C, about 55°C, about 56°C, about 57°C, about 58°C, about 59°C, about 60°C, about 61°C, about 62°C, about 63°C, about 64°C, about 65°C, about 66°C, about 67°C, about The elevated temperature is 68°C, about 69°C, about 70°C, about 71°C, about 72°C, about 73°C, about 74°C, about 75°C, about 76°C, about 77°C, about 78°C, about 79°C, about 80°C, about 81°C, about 82°C, about 83°C, about 84°C, about 85°C, about 86°C, about 87°C, about 88°C, about 89°C, about 90°C, about 91°C, about 92°C, about 93°C, about 94°C, about 95°C, about 96°C, about 97°C, about 98°C, about 99°C, or about 100°C. In some embodiments, the elevated temperature is about 70°C.

[0055] In some embodiments, the inert atmosphere for the emulsion polymerization reaction mixture is argon, hi other embodiments, the inert atmosphere is nitrogen.

[0056] In some embodiments, the emulsion polymerization reaction mixture is stirred at an elevated temperature for a period of about 3 to 8 hours, e.g., about 3 hours, about 3.5 hours, about 4 hours, about 4.5 hours, about 5 hours, about 5.5 hours, about 6 hours, about 6.5 hours, about 7 hours, about 7.5 hours, or about 8 hours. In some embodiments, the emulsion polymerization reaction mixture is stirred at an elevated temperature for about 4 hours. In other embodiments, the emulsion polymerization reaction mixture is stirred at an elevated temperature for about 6 hours.

[0057] In some embodiments, 3,4-diacetoxystyrene (DAS) is copolymerized with styrene via emulsion polymerization. In these embodiments, styrene and 3,4-diacetoxystyrene (DAS) are blended in a desired ratio with a chain transfer agent, such as n-dodecanethiol, to obtain a monomer blend. The amount of chain transfer agent can be varied to manipulate and control the molecular weight of the polymer. This monomer blend is added to a stirred aqueous solution of sodium lauryl sulfate, cetyl alcohol, potassium persulfate, and sodium bicarbonate at 65°C under argon to obtain an emulsion polymerization reaction mixture. After 4 hours, the emulsion polymerization reaction mixture is cooled to room temperature, precipitated into a brine solution, and filtered to obtain the protected polymer, poly(3,4-diacetoxystyrene-co-styrene).

[0058] In another embodiment, 3,4-diacetoxystyrene (DAS) is copolymerized with styrene via emulsion polymerization, in which styrene and 3,4-diacetoxystyrene (DAS) are blended in the desired ratio with a chain transfer agent, such as n-dodecanethiol, to obtain a monomer blend. The amount of chain transfer agent can be varied to manipulate and control the molecular weight of the polymer. This monomer blend is added to a stirred aqueous solution of sodium lauryl sulfate, cetyl alcohol, potassium persulfate, and sodium bicarbonate under nitrogen at 70°C to obtain the emulsion polymerization reaction mixture. After 6 hours, the emulsion polymerization reaction mixture is cooled, and the precipitated protected polymer, poly(3,4-diacetoxystyrene-co-styrene), is recovered by centrifugation.

[0059] In some embodiments, the polymerization is anionic. The polymerization is carried out in an organic solvent. DAS and styrene are blended together and dissolved in a solvent such as tetrahydrofuran or cyclohexane. Under an inert atmosphere such as nitrogen or argon, a radical initiator such as sec-butyllithium or n-butyllithium is added to the polymerization solution. The reaction solution is maintained at a temperature between -78°C and 25°C with constant stirring.

[0060] In some embodiments, after the polymerization reaction, the poly(3,4-diacetoxystyrene-co-styrene) polymer is isolated from the polymerization reaction mixture.

[0061] In some embodiments, the poly(3,4-diacetoxystyrene-co-styrene) polymer is isolated from the polymerization reaction mixture by precipitation and filtration.

[0062] In some embodiments, the poly(3,4-diacetoxystyrene-co-styrene) polymer can be precipitated by cooling the polymerization reaction mixture.

[0063] In other embodiments, the poly(3,4-diacetoxystyrene-co-styrene) polymer can be precipitated by mixing the polymerization reaction mixture with a salt solution.

[0064] In yet another embodiment, the poly(3,4-diacetoxystyrene-co-styrene) polymer can be precipitated by cooling the polymerization reaction mixture and mixing it with a salt solution. The precipitated polymer is then filtered and washed with a solvent such as water.

[0065] In other embodiments, an acid such as HCl is added to the emulsion to break the emulsion, precipitating the poly(3,4-diacetoxystyrene-co-styrene), which is then isolated by filtration. Such embodiments are advantageous because less water is required to precipitate the poly(3,4-diacetoxystyrene-co-styrene). Furthermore, the acid added to break the emulsion does not deprotect the poly(3,4-diacetoxystyrene-co-styrene).

[0066] In yet other embodiments, the poly(3,4-diacetoxystyrene-co-styrene) polymer can be precipitated by cooling the polymerization reaction mixture and then transferring the mixture to a centrifuge where the water is removed to obtain a protected polymer powder.

[0067] In some embodiments, the poly(3,4-diacetoxystyrene-co-styrene) polymers produced by the processes of the present disclosure have a molecular weight ranging from about 25,000 to about 1,100,000. In some embodiments, the poly(3,4-diacetoxystyrene-co-styrene) polymers produced by the processes of the present disclosure have a molecular weight ranging from about 25,000 to about 300,000, e.g., 25,000, 50,000, 75,000, 100,000, 125,000, 150,000, 175,000, 200,000, 225,000, 250,000, 275,000, or 300,000.

[0068] In some embodiments, the poly(3,4-diacetoxystyrene-co-styrene) polymer produced by the processes of the present disclosure has a polydispersity index (PDI) of about 2 to about 30, e.g., about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30. As used herein, the term polydispersity index refers to the ratio of weight average molecular weight to number average molecular weight. In some embodiments, the poly(3,4-diacetoxystyrene-co-styrene) polymer produced by the processes of the present disclosure has a polydispersity index (PDI) of about 2 to about 4, e.g., about 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, or 4.

[0069] In some embodiments, the emulsion polymerization reaction converts at least 95% of the monomers (DAS and styrene) to polymer, e.g., at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or at least 99.8% of the monomers (DAS and styrene). The degree of polymer conversion can be determined by methods known to those skilled in the art, including, for example, NMR, FTIR, or liquid chromatography. Deprotection

[0070] In some embodiments of the disclosed process, poly(3,4-diacetoxystyrene-co-styrene) polymer is deprotected to yield poly(catechol-styrene) (PCS), as shown in Scheme 2 below. This deprotection is achieved by subjecting the poly(3,4-diacetoxystyrene-co-styrene) polymer to conditions that cleave the acetate ester. Such conditions include treatment with aqueous acids such as, for example, hydrochloric acid (HCl), p-toluenesulfonic acid (p-TsOH), fluoroboric acid (HBF), and camphorsulfonic acid (CSA), or aqueous bases such as, for example, NaOH, KOH, NH, and methylamine (CHNH). Scheme 2 [ka]

[0071] In some embodiments of the disclosed process, poly(3,4-diacetoxystyrene-co-styrene) polymer is deprotected with acid to give poly(catechol-styrene) (PCS), as shown in Scheme 3. Scheme 3 [ka]

[0072] In some embodiments, the deprotection reaction is carried out by treating the poly(3,4-diacetoxystyrene-co-styrene) polymer with an acid. In some embodiments, the acid is selected from hydrochloric acid (HCl), p-toluenesulfonic acid (p-TsOH), fluoroboric acid (HBF), camphorsulfonic acid (CSA), and nitric acid, and combinations thereof. In some embodiments, the acid is HCl.

[0073] In some embodiments, the deprotection reaction is carried out by treating the poly(3,4-diacetoxystyrene-co-styrene) polymer with an amount of acid from 0.9 mmol to 1.9 mmol per gram of poly(3,4-diacetoxystyrene-co-styrene) polymer, e.g., 0.9, 0.91, 0.92, 0.93 mmol per gram of poly(3,4-diacetoxystyrene-co-styrene) polymer. ,0.94,0.95,0.96,0.97,0.98,0.99,1.0,1.01,1.02,1.03,1.04,1.05,1.06,1.07,1.08,1.09,1.1,1.11,1.12,1.13,1.14,1.15,1.16,1.17,1.18,1.19,1.2,1.21,1.22,1.23,1.24,1.25,1.26,1.27 , 1.28, 1.29, 1.3, 1.31, 1.32, 1.33, 1.34, 1.35, 1.36, 1.37, 1.38, 1.39, 1.4, 1.41, 1.42, 1.43, 1.44, 1.45, 1.46, 1.47, 1.48, 1.49, 1.5, 1.51, 1.52, 1.53, 1.54, 1.55, 1.56, 1.57, 1.58, 1.59, 1.6, 1.61 , 1.62, 1.63, 1.64, 1.65, 1.66, 1.67, 1.68, 1.69, 1.7, 1.71, 1.72, 1.73, 1.74, 1.75, 1.76, 1.77, 1.78, 1.79, 1.8, 1.81, 1.82, 1.83, 1.84, 1.85, 1.86, 1.87, 1.88, 1.89, or 1.9 mmol of acid.

[0074] In some embodiments, the deprotection reaction is carried out by treating the poly(3,4-diacetoxystyrene-co-styrene) polymer with an acid in an amount of 1.4 to 1.5 mmol of acid per gram of poly(3,4-diacetoxystyrene-co-styrene) polymer, e.g., 1.4, 1.41, 1.42, 1.43, 1.44, 1.45, 1.46, 1.47, 1.48, 1.49, or 1.5 mmol of acid per gram of poly(3,4-diacetoxystyrene-co-styrene) polymer.

[0075] In some embodiments, the acid is a 1 M to 8 M solution, e.g., 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4, 4.1, 4.2, 4.3, 4.4 , 4.5, 4.6, 4.7, 4.8, 4.9, 5, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, or 8M acid solution is added to the deprotection reaction.

[0076] In some embodiments, the acid is added to the deprotection reaction as a 4M to 8M solution, for example, a 4, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, or 8M acid solution.

[0077] In some embodiments, the deprotection reaction is carried out by treating the poly(3,4-diacetoxystyrene-co-styrene) polymer with hydrochloric acid (HCl). In some embodiments, the HCl is used in a range of 1 M to 8 M solution, e.g., 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 4.10, 4.11, 4.12, 4.13, 4.14, 4.15, 4.16, 4.17, 4.18, 4.19, 4.20, 4.21, 4.22, 4.23, 4.24, 4.25, 4.26, 4.27, 4.28, 4.29, 4.30, 4.31, 4.32, 4.33, 4.34, 4.35, 4.36, 4.37, 4.38, 4.39, 4.39, 4.39, 4.39, 4.31, 4.32, 4.33, 4.34, 4.35, 4.36, 4.37, 4.38, 4.39, It is added to the deprotection reaction as a 4, 4.5, 4.6, 4.7, 4.8, 4.9, 5, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, or 8M acid solution.

[0078] In other embodiments, HCl is added to the deprotection reaction as a 4M to 8M solution, such as, for example, a 4, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, or 8M HCl solution.

[0079] In some embodiments, the deprotection reaction is carried out by treating the poly(3,4-diacetoxystyrene-co-styrene) polymer with 6 M HCl.

[0080] In some aspects of the deprotection reaction, the poly(3,4-diacetoxystyrene-co-styrene) polymer is dissolved in a solvent, such as THF, acetone, or dimethylformamide (DMF). In some embodiments of the deprotection reaction, the solvent is THF. In some embodiments of the deprotection reaction, the solvent is acetone. In other embodiments of the deprotection reaction, the solvent is dimethylformamide (DMF).

[0081] In some embodiments of the deprotection reaction, the poly(3,4-diacetoxystyrene-co-styrene) polymer is dissolved in a solvent at a concentration of 280 to 500 grams of poly(3,4-diacetoxystyrene-co-styrene) polymer per liter of solvent.

[0082] In some embodiments of the deprotection reaction, the poly(3,4-diacetoxystyrene-co-styrene) polymer is prepared by reacting 280 to 345 grams of poly(3,4-diacetoxystyrene-co-styrene) polymer per liter of solvent, e.g., 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304 , 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, or 345 grams of poly(3,4-diacetoxystyrene-co-styrene) polymer dissolved in a solvent.

[0083] In some embodiments of the deprotection reaction, the reaction mixture is heated to an elevated temperature, e.g., from about 40°C to about 100°C, e.g., about 40°C, about 41°C, about 42°C, about 43°C, about 44°C, about 45°C, about 46°C, about 47°C, about 48°C, about 49°C, about 50°C, about 51°C, about 52°C, about 53°C, about 54°C, about 55°C, about 56°C, about 57°C, about 58°C, about 59°C, about 60°C, about 61°C, about 62°C, about 63°C, about 64°C, about 65°C, about 66°C, or about 100°C.

[0084] In some embodiments of the deprotection reaction, the reaction mixture is heated to about 70°C.

[0085] In other embodiments of the deprotection reaction, the reaction mixture is heated to the reflux temperature of the solvent.

[0086] In some embodiments, the deprotection reaction is allowed to proceed for up to 48 hours, e.g., 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, 24 hours, 25 hours, 26 hours, 27 hours, 28 hours, 29 hours, 30 hours, 31 hours, 32 hours, 33 hours, 34 hours, 35 hours, 36 hours, 37 hours, 38 hours, 39 hours, 40 hours, 41 hours, 42 hours, 43 hours, 44 hours, 45 hours, 46 hours, 47 hours, or 48 hours. In some embodiments, the deprotection reaction is allowed to proceed for 24 hours. In some embodiments, the deprotection reaction is allowed to proceed for 48 hours.

[0087] In some embodiments, after deprotection, the reaction mixture is neutralized with a base such as sodium bicarbonate.

[0088] In some embodiments of the present disclosure, the deprotection reaction results in at least 90% deprotection, for example, at least 90% deprotection, at least 91% deprotection, at least 92% deprotection, at least 93% deprotection, at least 94% deprotection, at least 95% deprotection, at least 96% deprotection, at least 97% deprotection, at least 98% deprotection, at least 99% deprotection, or 100% deprotection. As used herein, % deprotection refers to the percentage of acetoxy-protected catechol hydroxyl groups converted to catechol hydroxyl groups (i.e., deprotected catechol hydroxyl groups) in the PCS polymer. % deprotection can be measured by standard techniques, such as NMR.

[0089] In some embodiments, the deprotection reaction results in at least 95% deprotection.

[0090] In some embodiments, the deprotection product, poly(catechol-styrene) polymer, is isolated by precipitation and filtration. For example, in some embodiments, the poly(catechol-styrene) polymer is precipitated by cooling the deprotection reaction mixture to about 25-35°C and then adding a solvent (i.e., an anti-solvent) such as water to the reaction mixture. In other embodiments, the poly(catechol-styrene) polymer is precipitated by cooling the deprotection reaction mixture to about 25-35°C and then adding the reaction mixture to an anti-solvent such as water.

[0091] In some embodiments, the poly(catechol-styrene) polymer is precipitated by cooling the deprotection reaction mixture to about 25-35° C. and then adding the reaction mixture to water. In some embodiments, the poly(catechol-styrene) polymer is precipitated by cooling the deprotection reaction mixture to about 25-35° C. and then adding the reaction mixture to deionized water.

[0092] After precipitation, the precipitate can then be collected by filtration.

[0093] In some embodiments, the poly(catechol-styrene) polymer precipitate is redissolved in a solvent, such as a polar solvent. Examples of polar solvents include acetone, dichloromethane, methyl ethyl ketone, and DMF. The poly(catechol-styrene) polymer can then be precipitated by adding a non-polar solvent, such as hexane or ether. In some embodiments, the poly(catechol-styrene) polymer can be redissolved three times and isolated by removing the solvent by evaporation.

[0094] In another embodiment, the poly(catechol-styrene) polymer precipitate is dissolved in a solvent, such as acetone or THF. The resulting solution is then added in portions to water to precipitate the poly(catechol-styrene) polymer. This procedure of dissolving in a solvent and then adding the resulting solution in portions to water can be repeated any number of times.

[0095] In another embodiment, the poly(catechol-styrene) polymer precipitate is dissolved in a solvent, such as acetone or THF. The resulting solution is then added in portions to a poor solvent, such as hexane, to precipitate the poly(catechol-styrene) polymer. This procedure of dissolving in a solvent and then adding the resulting solution in portions to a poor solvent can be repeated any number of times.

[0096] In some embodiments, the solvent is removed by evaporation and the poly(catechol-styrene) polymer is dissolved in a polar solvent such as acetone. The acetone solution may be evaporated to yield a solid poly(catechol-styrene) polymer, or may be spray-dried to yield a solid poly(catechol-styrene) polymer.

[0097] The deprotection and isolation steps can be difficult and therefore currently rely on significant manual labor, as sticky, partially solvated, precipitated poly(catechol-styrene) polymers can be difficult to work with and pose challenges to automated manufacturing.

[0098] In some embodiments, the protected polymer, poly(3,4-diacetoxystyrene-co-styrene), is dissolved in tetrahydrofuran (THF) at 45°C. Once completely dissolved, 6 molar hydrochloric acid (HCl) is added and the reaction is refluxed at 70°C overnight. The next day, the reaction is cooled to room temperature and precipitated into stirred water. The water is decanted, and the polymer is dissolved in acetone and partially precipitated into stirred hexane. The hexane is decanted, and the polymer is recovered and dried via vacuum oven.

[0099] In other embodiments, deprotection is carried out by treating the poly(3,4-diacetoxystyrene-co-styrene) polymer with a base such as potassium hydroxide. The reaction mixture is neutralized and the product is isolated by precipitation and redissolution as described above.

[0100] In some embodiments, the polymerization and deprotection synthesis steps are carried out in the same reaction vessel without isolating the intermediate protected polymer. The resulting poly(catechol-styrene) polymer can be emulsified and spray-dried or solidified, such as by adding salt. The solidified poly(catechol-styrene) polymer can be purified by washing with a solvent such as water.

[0101] In some embodiments, the poly(catechol-styrene) produced by this process has a molecular weight in the range of 15,000 to 1,000,000, for example, 15,000 to 188,000, as measured by GPC.

[0102] In other embodiments, the poly(catechol-styrene) produced by the processes of the present disclosure has a molecular weight of about 50,000 to about 400,000, e.g., about 50,000, 75,000, 100,000, 125,000, 150,000, 175,000, 200,000, 225,000, 250,000, 275,000, 300,000, 325,000, 350,000, 375,000, or 400,000.

[0103] Tensile tests were performed using aluminum lap shear and Instron. The average strength of the PCS of different molecular weights was compared to that of PCS made from dimethoxyacetophenone monomer, showing optimal performance at 80,000 molecular weight. Despite the different processing methods, the average strength of the different 80,000 molecular weight PCS showed no significant differences. Furthermore, a peak strength was observed at 122,000 molecular weight for PCS made by this process. This was surprising, as literature indicates that PCS strength increases up to the 80,000-100,000 molecular weight range and then begins to decrease.

[0104] In some embodiments, the poly(catechol-styrene) polymer has a polydispersity index (PDI) of about 1 to about 4, e.g., about 1, about 1.1, about 1.2, about 1.3, about 1.4, about 1.5, about 1.6, about 1.7, about 1.8, about 1.9, about 2, about 2.1, about 2.2, about 2.3, about 2.4, about 2.5, about 2.6, about 2.7, about 2.8, about 2.9, about 3, about 3.1, about 3.2, about 3.3, about 3.4, about 3.5, about 3.6, about 3.7, about 3.8, about 3.9, or about 4, as measured by GPC.

[0105] In other embodiments, the poly(catechol-styrene) polymer has a polydispersity index (PDI) of about 2 to about 4, e.g., about 2, about 2.1, about 2.2, about 2.3, about 2.4, about 2.5, about 2.6, about 2.7, about 2.8, about 2.9, about 3, about 3.1, about 3.2, about 3.3, about 3.4, about 3.5, about 3.6, about 3.7, about 3.8, about 3.9, or about 4, as measured by GPC.

[0106] In yet other embodiments, the poly(catechol-styrene) polymer has a polydispersity index (PDI) of about 2 to about 4, e.g., about 2, about 2.1, about 2.2, about 2.3, about 2.4, about 2.5, about 2.6, about 2.7, about 2.8, about 2.9, or about 3, as measured by GPC.

[0107] The emulsion polymerization process described herein is advantageous because it results in extremely high monomer conversions, often 99% or greater. As a result of this high degree of monomer conversion, the amount of unreacted monomer that must be removed from the product is minimized. Removal of unreacted monomer is made difficult by the heat and air sensitivity of the product polymer.

[0108] As described above, the disclosed PCS manufacturing process includes a polymerization reaction and a deprotection reaction. In some embodiments, the polymerization reaction and the deprotection reaction are carried out in separate reaction vessels. In other embodiments, the polymerization reaction and the deprotection reaction are carried out in the same reaction vessel, i.e., a "one-pot" process.

[0109] Different applications of PCS polymers may require different catechol contents. The catechol content of the resulting PCS polymer can be controlled by adjusting the reaction conditions of the processes described herein. For example, the catechol content may be controlled by adjusting the weight ratio of the styrene monomer to the DAS monomer used in the emulsion polymerization reaction, adjusting the amount of surfactant in the emulsion polymerization reaction, adjusting the amount of initiator used in the emulsion polymerization reaction, or adjusting the amount of chain transfer agent used in the emulsion polymerization reaction. In some embodiments, the catechol content of the PCS polymers produced by the disclosed processes ranges from about 10% to about 75% by weight, e.g., about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, about 37%, about 38%, or about 39% by weight. The amount is about 39%, about 40%, about 41%, about 42%, about 43%, about 44%, about 45%, about 46%, about 47%, about 48%, about 49%, about 50%, about 51%, about 52%, about 53%, about 54%, about 55%, about 56%, about 57%, about 58%, about 59%, about 60%, about 61%, about 62%, about 63%, about 64%, about 65%, about 66%, about 67%, about 68%, about 69%, about 70%, about 71%, about 72%, about 73%, about 74%, or about 75% by weight.

[0110] In some embodiments, the catechol content of the PCS polymer produced by the disclosed process is about 75% by weight.

[0111] In some aspects, the present disclosure relates to a polymerization reaction end product comprising a poly(3,4-diacetoxystyrene-co-styrene) polymer, wherein the unconverted monomer present in the reaction end product is less than 5%, e.g., less than 5%, less than 4%, less than 3%, less than 2%, less than 1%, less than 0.5%, or less than 0.1%, of the monomer added to the reaction mixture. In some embodiments, the unconverted monomer present in the reaction mixture is less than 1% of the monomer added to the reaction mixture.

[0112] In some aspects, the present disclosure relates to a polymerization reaction end product comprising a PCS polymer, wherein the unconverted monomer present in the reaction end product is less than 5% of the monomer added to the reaction mixture, e.g., less than 5%, less than 4%, less than 3%, less than 2%, less than 1%, less than 0.5%, or less than 0.1%. In some embodiments, the unconverted monomer present in the reaction mixture is less than 1% of the monomer added to the reaction mixture.

[0113] The disclosed PCS process has several distinct advantages over PCS processes using methoxycatechol protecting groups. First, from an economic perspective, PCS processes using methoxycatechol protecting groups require expensive deprotection reagents, making those processes economically burdensome. In contrast, the disclosed process using acetate protecting groups requires much less expensive deprotection reagents. Second, processes using methoxycatechol protecting groups require much higher temperatures (165°C) to achieve deprotection. As a result, the deprotection reaction requires a high-boiling-point solvent, such as DMF. This higher-boiling-point solvent can be difficult to completely remove during the drying process and may therefore compromise the suitability of the resulting PCS for certain uses or applications. For example, the FDA restricts the amount of certain residual solvents for safety reasons, which could prevent the use of PCS made from methoxycatechol protecting groups in biomedical applications. The use of certain high-boiling-point solvents also precludes the potential use of spray drying for large-scale PCS production. The disclosed process avoids all of these issues.

[0114] In this disclosure, the singular forms "a," "an," and "the" include plural references, and reference to a particular numerical value includes at least that particular value unless the context clearly dictates otherwise. Thus, for example, reference to "one material" is a reference to at least one of such materials and equivalents thereof known to those of ordinary skill in the art, and so forth.

[0115] The modifier "about" should be considered to disclose a range defined by the absolute values ​​of the two endpoints. For example, the expression "about 2 to about 4" also discloses the range "2 to 4." When used to modify a single number, the term "about" can refer to ±10% of the indicated number and is inclusive of the indicated number. For example, "about 10%" can indicate a range of 9% to 11%, and "about 1" means 0.9 to 1.1.

[0116] When lists are presented, it is to be understood that each individual element of that list, and every combination of that list, is to be construed as a separate embodiment unless otherwise stated. For example, a list of embodiments presented as "A, B, or C" should be construed as including the embodiments "A," "B," "C," "A or B," "A or C," "B or C," or "A, B, or C."

[0117] Where present, all ranges are inclusive and combinable; i.e., reference to values ​​stated in ranges includes all values ​​within that range. For example, a range defined as 400 to 450 ppm includes 400 ppm and 450 ppm as independent embodiments. The ranges 400 to 450 ppm and 450 to 500 ppm can be combined to form the range 400 to 500 ppm. Furthermore, for the description of a range herein where two or more specific values ​​of a parameter are recited, the present disclosure also includes a value selected from the range defined by any two of the two or more specific values ​​of that parameter, inclusive of the endpoints of such ranges.

[0118] For clarity, it should be understood that certain features of the invention that are described herein in the context of separate embodiments may also be provided in combination in a single embodiment. That is, unless clearly incompatible or excluded, each individual embodiment is deemed combinable with any other embodiment(s), and such combinations are considered to be separate embodiments. Conversely, various features of the invention that are, for brevity, described in the context of a single embodiment, may also be provided separately or in any subcombination. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as a guide for the use of exclusive terminology such as "solely," "only," and the like in connection with the recitation of claim elements or the use of "negative" limitations. Finally, while an embodiment may be described as part of a series of steps or part of a more general structure, each such step may also be considered a separate embodiment in itself.

[0119] The present disclosure has been illustrated by the description of several embodiments, and while the exemplary embodiments have been described in considerable detail, it is not the intention of the applicant to limit, or in any way limit, the scope of the appended claims to such detail. Further advantages and modifications may be readily apparent to those skilled in the art. Furthermore, features from separate listings may be combined, and features from the examples may be generalized throughout the disclosure.

[0120] The present disclosure is also directed to the following aspects:

[0121] Aspect 1: A method of forming a poly(catechol-styrene) polymer, comprising: (i) polymerizing 3,4-diacetoxystyrene and styrene by emulsion polymerization to form poly(3,4-diacetoxystyrene-co-styrene) polymer; (ii) deprotecting the acetate groups of the resulting poly(3,4-diacetoxystyrene-co-styrene) polymer to form a poly(catechol-styrene) polymer; 1. A method for forming a poly(catechol-styrene) polymer, comprising:

[0122] Embodiment 2: The method of embodiment 1, wherein after the poly(3,4-diacetoxystyrene-co-styrene) polymer is formed, it is precipitated.

[0123] Embodiment 3: The method of embodiment 2, wherein the precipitated poly(3,4-diacetoxystyrene-co-styrene) polymer is deprotected by dissolving in a solution and treating with an acid.

[0124] Embodiment 4: The method of embodiment 1, wherein the polymerizing step further comprises a surfactant, an initiator, and a chain transfer agent.

[0125] Embodiment 5: The method of embodiment 4, wherein the initiator comprises potassium persulfate.

[0126] Embodiment 6: The method of embodiment 4, wherein the chain transfer agent comprises dodecyl thiol.

[0127] Embodiment 7: The method of embodiment 1, wherein the polymerization and deprotection steps are performed in one pot.

[0128] Embodiment 8: The method of embodiment 1, wherein after the poly(catechol-styrene) polymer is formed, it is precipitated.

[0129] Embodiment 9: The method of embodiment 8, wherein the precipitated poly(catechol-styrene) polymer is dissolved in a polar solvent and then precipitated from a non-polar solvent.

[0130] Embodiment 10: The method of embodiment 1, wherein the poly(3,4-diacetoxystyrene-co-styrene) polymer is deprotected by treatment with acid.

[0131] Embodiment 11: The method of embodiment 10, wherein after treatment with acid, the mixture is neutralized with a base, concentrated to a solid, and the poly(catechol-styrene) polymer is dissolved in a polar solvent.

[0132] 12. The method of embodiment 11, wherein the dissolved poly(catechol-styrene) polymer is spray dried.

[0133] Example 13: A poly(catechol-styrene) polymer formed by the process described in Example 1.

[0134] Example 14: The poly(catechol-styrene) polymer of example 13, wherein the poly(catechol-styrene) polymer has a molecular weight of 15k to 188k as measured by GPC.

[0135] Example 15: The poly(catechol-styrene) polymer of example 13, wherein the poly(catechol-styrene) polymer has a polydispersity index (PDI) of 2 to 3 as measured by GPC. [Example]

[0136] Example 1 - Preparation of diacetoxy-protected poly(catechol-styrene) Styrene (300 milliliters) and diacetoxystyrene (200 grams) were blended with n-dodecanethiol (5 milliliters) in an Erlenmeyer flask equipped with a magnetic stirrer. The monomer blend was stirred with simultaneous argon bubbling throughout. An aqueous solution (1500 milliliters) of sodium lauryl sulfate (3.82 grams), cetyl alcohol (9.65 grams), potassium persulfate (10.63 grams), and sodium bicarbonate (0.001 grams) was prepared in a three-neck round-bottom flask equipped with an overhead stirrer. The emulsion solution was stirred and heated to 65°C using a heating mantle for 1 hour. Argon was then bubbled through for 1 hour. The emulsion was stirred at 200 rpm, and the monomer blend was added. The stirring was increased to 530 rpm, and the temperature was raised to 70°C. The polymerization was carried out overnight. The next day, the reaction mixture was cooled to room temperature and poured into a stirred saturated solution of brine (15,000 milliliters) to precipitate the polymer. The brine solution was stirred for 1 hour, after which the stirring was stopped and the polymer was allowed to stand for 1 hour. The polymer was recovered by vacuum filtration and proceeded to deprotection without being completely dried.

[0137] Example 2 - Preparation of Poly(catechol-styrene) Diacetoxy-protected poly(catechol-styrene) (233 grams) was added to a round-bottom flask equipped with a magnetic stirrer and reflux condenser. 1200 milliliters of tetrahydrofuran was added, and the solution was stirred at 45°C using a heating mantle until the polymer was completely dissolved. 6 molar hydrochloric acid (100 milliliters) was added. The temperature was raised to 70°C, and the reaction was heated for at least 16 hours. The reaction was then cooled to room temperature and precipitated into stirred water (15,000 milliliters). The polymer was stirred for one hour, after which the stirring was stopped and the polymer was allowed to settle for an additional hour. The water was then decanted, and the polymer was dissolved in acetone (1,000 milliliters). The acetone-polymer solution was precipitated dropwise into stirred hexane (15,000 milliliters). The polymer was stirred for one hour, after which the stirring was stopped and the polymer was allowed to settle for an additional hour. The decanted hexane and polymer were collected and dried in a vacuum oven. Yield: 145 grams (71%).

[0138] Example 3 - Polymer Molecular Weight The amounts of initiator and chain transfer agent (CTA) were varied to determine their effect on polymer molecular weight, and the results are shown in Figures 1 and 2.

[0139] Example 4 (Comparative) - Polymerization Reaction The polymerization reactions were carried out using various amounts of reagents. [ka] [Table 1] The detergent was 10 mM SDS.

[0140] Example 5 (Comparative) - Deprotection Reaction Deprotection reactions were carried out using various amounts of reagents. [ka] [Table 2] *Emulsion

[0141] Example 6 - Dry Adhesion Strength The dry adhesive strength of poly(catechol-styrene) polymers produced by processes using diacetoxy and methoxy protecting groups was compared along with their molecular weights, and the results are shown in Figure 3.

[0142] Example 7 - Wet Adhesion Strength The wet adhesive strength of poly(catechol-styrene) polymers produced by processes using diacetoxy and methoxy protecting groups was compared along with their molecular weights, and the results are shown in Figure 4.

[0143] Example 8 - Poly(catechol-styrene) polymer manufacturing process The production of (PCS) on a pilot scale involves three main steps: 1. monomer synthesis, 2. emulsion polymerization, and 3. deprotection of the protected polymer to produce PCS.

[0144] Monomer Synthesis. In this first step, a 500 L reactor is charged with dimethylformamide and dispensed from an IBC tote. Caffeic acid powder is added and heated until completely dissolved. Triethylamine is pumped from the tote into the reactor and heated to 110°C for 2 hours. The reactor is then cooled to 25°C, and acetic anhydride is pumped into the reactor. After stirring for 10 hours, the reaction solution is pumped into a storage vessel. The monomer is isolated using a liquid-liquid extraction unit. The reaction solution is diluted with water and extracted with ether. The ether solution of the monomer is then treated with 1 M HCl, followed by a NaCO3 (aq) wash and a NaCl wash. The ether is removed from the purified monomer in an evaporation unit. The ether is then recycled for use in subsequent batches.

[0145] Emulsion Polymerization. This second step is the copolymerization of the diacetoxy monomer (DAS) produced in step 1 with commercially obtained styrene in an emulsion process. Sodium lauryl sulfate, cetyl alcohol, potassium persulfate, and sodium bicarbonate are dissolved in water in a 500 L reactor while bubbling with nitrogen. Styrene, DAS, and n-dodecylthiol are blended in a 200 L tank while bubbling with nitrogen. The monomer blend is added to the 500 L tank and heated to 70 °C for 6 hours under constant agitation. After cooling, the emulsion is transferred to a centrifuge, and the water is removed to obtain the protected polymer powder, poly(3,4-diacetoxystyrene-co-styrene).

[0146] Deprotection. This final step involves deprotecting the protected polymer to produce PCS. A 1000 L reactor is charged with tetrahydrofuran and poly(3,4-diacetoxystyrene-co-styrene) polymer. The reactor is heated to 70 °C and 6 M HCl is added. After 24 hours, the reaction mixture is cooled and precipitated into a 5000 L tank containing water. The water / THF mixture is drained from the tank, leaving behind the solid precipitated PCS, which is sent to a recovery column, allowing both THF and process water to be recycled for use in subsequent batches. Acetone is thoroughly sprayed throughout the tank to recover all of the PCS. After the polymer is completely dissolved in the acetone, the solution is filtered and pumped to a storage tank. The solution is then sent to a continuous spray dryer for solvent removal, yielding dry powder PCS. Example 9 - PCS synthesis results Polymerization reaction [Table 3-1] [Table 3-2] [Table 3-3] [Table 3-4] [Table 4]

Claims

1. 1. A method for forming a poly(catechol-styrene) polymer, comprising: (i) polymerizing 3,4-diacetoxystyrene (DAS) monomers and styrene monomers in an emulsion polymerization reaction to form a poly(3,4-diacetoxystyrene-co-styrene) polymer; (ii) deprotecting the acetate groups of the resulting poly(3,4-diacetoxystyrene-co-styrene) polymer to form a poly(catechol-styrene) polymer.

2. 10. The process of claim 1, wherein the weight ratio of styrene monomer to DAS monomer used in the emulsion polymerization reaction of step (i) is from about 0.1 to about 5.

0.

3. 10. The process of claim 1, wherein the weight ratio of styrene monomer to DAS monomer used in the emulsion polymerization reaction of step (i) is from about 1.1 to about 1.

9.

4. 10. The method of claim 1, wherein the emulsion polymerization reaction of step (i) comprises a styrene monomer, a DAS monomer, a surfactant, an initiator, and a chain transfer agent.

5. The method of claim 4 wherein the surfactant is sodium lauryl sulfate.

6. The method of claim 4 wherein the surfactant is cetyl alcohol.

7. 5. The method of claim 4, wherein the surfactant is a mixture of sodium lauryl sulfate and cetyl alcohol.

8. 8. The method of any one of claims 4 to 7, wherein the weight ratio of sodium lauryl sulfate (SLS) to total monomers (styrene + DAS), expressed as a percentage, is from about 0.2% to about 6.0%, said percentage being calculated as (weight of SLS) / (weight of DAS + weight of styrene)*100.

9. 9. The method of claim 8, wherein the weight ratio of sodium lauryl sulfate (SLS) to total monomers (styrene + DAS), expressed as a percentage, is from about 0.8% to about 3.0%.

10. 10. The method of any one of claims 4 to 9, wherein the weight ratio of cetyl alcohol to total monomers (styrene + DAS), expressed as a percentage, is from about 0.5% to about 10.0%, said percentage being calculated as (weight of cetyl alcohol) / (weight of DAS + weight of styrene)*100.

11. 11. The method of claim 10, wherein the weight ratio of cetyl alcohol to total monomers (styrene + DAS), expressed as a percentage, is from about 2.0% to about 7.0%.

12. 12. The method of any one of claims 7 to 11, wherein the weight ratio of cetyl alcohol to sodium lauryl sulfate is from about 2.0 to about 4.

0.

13. 13. The method of claim 12, wherein the weight ratio of cetyl alcohol to sodium lauryl sulfate is from about 2.30 to about 2.

80.

14. The method of any one of claims 4 to 13, wherein the initiator is a water-soluble free radical initiator.

15. 15. The method of claim 14, wherein the ratio of initiator to total monomers, expressed as a percentage, is from about 0.1% to about 3.0%, said percentage being calculated as (weight of initiator) / (weight of DAS+weight of styrene)*100.

16. 16. The method of claim 15, wherein the ratio of initiator to total monomer, expressed as a percentage, is from about 1.0% to about 3.0%.

17. The method of any one of claims 4 to 16, wherein the initiator is sodium persulfate, potassium persulfate, ammonium persulfate, benzoyl peroxide, or t-butyl hydroperoxide.

18. 18. The method of any one of claims 4 to 17, wherein the chain transfer agent is dodecylthiol (also known as dodecyl mercaptan or n-dodecanethiol), carbon tetrachloride, or a halocarbon.

19. 20. The method of claim 18, wherein the ratio of chain transfer agent to total monomers, expressed as a percentage, is from about 0.05% to about 10%, said percentage being calculated as (weight of chain transfer agent) / (weight of DAS+weight of styrene)*100.

20. 20. The method of claim 18 or claim 19, wherein the chain transfer agent is dodecyl thiol.

21. 21. The method of any one of claims 1 to 20, wherein the emulsion polymerization reaction (i) also includes a buffer such as sodium bicarbonate.

22. 22. The method of any one of claims 1 to 21, wherein the emulsion polymerization reaction (i) also comprises an aqueous solvent, such as water.

23. 23. The method of any one of claims 1 to 22, wherein the amount of water used in the emulsion polymerization reaction is a function of the total monomers used, from about 190 to about 320 grams of total monomers per liter of water.

24. 24. The method of any one of claims 1 to 23, wherein the emulsion polymerization reaction is carried out at an elevated temperature of from about 40°C to about 100°C.

25. 25. The method of claim 24, wherein the emulsion polymerization reaction is carried out at a temperature of about 70°C.

26. The method of any one of claims 1 to 25, wherein the emulsion polymerization reaction is carried out under an argon or nitrogen atmosphere.

27. 27. The method of any one of claims 1 to 26, wherein the emulsion polymerization reaction is stirred at an elevated temperature for a period of about 3 to 8 hours.

28. The method of any one of claims 1 to 27, wherein the poly(3,4-diacetoxystyrene-co-styrene) polymer is isolated from the polymerization reaction mixture.

29. 29. The method of claim 28, wherein the poly(3,4-diacetoxystyrene-co-styrene) polymer is isolated from the polymerization reaction mixture by precipitation and filtration.

30. 30. The method of claim 29, wherein the poly(3,4-diacetoxystyrene-co-styrene) polymer is precipitated by cooling the polymerization reaction mixture.

31. 30. The method of claim 29, wherein the poly(3,4-diacetoxystyrene-co-styrene) polymer is precipitated by mixing the polymerization reaction mixture with a salt solution.

32. 32. The method of any one of claims 29 to 31, wherein the poly(3,4-diacetoxystyrene-co-styrene) polymer is precipitated by cooling the polymerization reaction mixture and mixing with a salt solution.

33. The method of any one of claims 29 to 32, wherein the precipitated polymer is filtered and washed with a solvent such as water.

34. 34. The method of any one of claims 1 to 33, wherein the poly(3,4-diacetoxystyrene-co-styrene) polymer is precipitated by cooling the polymerization reaction mixture and then isolated by transferring the mixture to a centrifuge where the water is removed to obtain a protected polymer powder.

35. 35. The method of any one of claims 1 to 34, wherein the poly(3,4-diacetoxystyrene-co-styrene) polymer produced by emulsion polymerization has a molecular weight ranging from about 25,000 to about 1,100,000.

36. 36. The method of claim 35, wherein the poly(3,4-diacetoxystyrene-co-styrene) polymer produced by the emulsion polymerization has a molecular weight ranging from about 25,000 to about 300,000.

37. 37. The method of any one of claims 1 to 36, wherein the poly(3,4-diacetoxystyrene-co-styrene) polymer produced by emulsion polymerization has a polydispersity index (PDI) of from about 2 to about 30.

38. 38. The method of claim 37, wherein the poly(3,4-diacetoxystyrene-co-styrene) polymer produced by emulsion polymerization has a polydispersity index (PDI) of from about 2 to about 4.

39. 39. The process of any one of claims 1 to 38, wherein the emulsion polymerization reaction results in a conversion of at least 95% of the total monomers (DAS + styrene) to polymer.

40. 40. The method of any one of claims 1 to 39, wherein the deprotection reaction, step (ii), is carried out by treating the poly(3,4-diacetoxystyrene-co-styrene) polymer with aqueous acid.

41. The aqueous acid is selected from the group consisting of hydrochloric acid (HCl), p-toluenesulfonic acid (p-TsOH), fluoroboric acid (HBF ４ ), camphorsulfonic acid (CSA) and nitric acid, and combinations thereof.

42. 42. The method of claim 40 or claim 41, wherein the deprotection reaction is carried out by treating the poly(3,4-diacetoxystyrene-co-styrene) polymer with acid in an amount of 0.9 to 1.9 mmol of acid per gram of poly(3,4-diacetoxystyrene-co-styrene) polymer.

43. 43. The method of claim 42, wherein the deprotection reaction is carried out by treating the poly(3,4-diacetoxystyrene-co-styrene) polymer with acid in an amount of 1.4 to 1.5 mmol of acid per gram of poly(3,4-diacetoxystyrene-co-styrene) polymer.

44. 44. The method of any one of claims 40 to 43, wherein the acid is added to the deprotection reaction as a 1M to 8M solution.

45. 45. The method of any one of claims 40 to 44, wherein the acid is HCl.

46. 46. ​​The method of claim 45, wherein the deprotection reaction is carried out by treating the poly(3,4-diacetoxystyrene-co-styrene) polymer with 6M HCl.

47. 47. The method of any one of claims 1 to 46, wherein the deprotection reaction comprises dissolving the poly(3,4-diacetoxystyrene-co-styrene) polymer in a solvent.

48. 48. The method of claim 47, wherein the solvent is acetone, THF, or dimethylformamide (DMF).

49. 49. The method of claim 47 or claim 48, wherein the poly(3,4-diacetoxystyrene-co-styrene) polymer is dissolved in the solvent at a concentration of 280 to 500 grams of poly(3,4-diacetoxystyrene-co-styrene) polymer per liter of solvent.

50. 50. The method of any one of claims 40 to 49, wherein the deprotection reaction is carried out by heating the reaction mixture to an elevated temperature, such as from about 40°C to about 100°C.

51. 51. The method of claim 50, wherein the deprotection reaction is carried out by heating the reaction mixture to about 70°C.

52. 52. The method of any one of claims 1 to 51, wherein the deprotection reaction is allowed to proceed for up to 48 hours.

53. 53. The method of any one of claims 40 to 52, wherein after deprotection, the deprotection reaction mixture is neutralized by the addition of a base such as sodium bicarbonate.

54. 54. The method of any one of claims 1 to 53, wherein the poly(catechol-styrene) polymer is isolated by precipitation and filtration.

55. 55. The method of claim 54, wherein the poly(catechol-styrene) polymer is precipitated by cooling the deprotection reaction mixture to about 25-35° C. and then adding a solvent, such as water, to the reaction mixture.

56. 56. The method of claim 54 or claim 55, wherein the precipitated poly(catechol-styrene) polymer is recovered by filtration.

57. 57. The method of any one of claims 54 to 56, wherein the poly(catechol-styrene) polymer precipitate is redissolved in a polar solvent such as acetone, dichloromethane, methyl ethyl ketone, and DMF.

58. 58. The method of claim 57, wherein the solvent is acetone.

59. 59. The method of claim 57 or claim 58, wherein the dissolved poly(catechol-styrene) polymer is precipitated by the addition of a non-polar solvent such as hexane or ether.

60. 59. The method of claim 57 or claim 58, wherein the dissolved poly(catechol-styrene) polymer is precipitated by evaporation to remove the solvent.

61. 59. The method of claim 57 or claim 58, wherein the dissolved poly(catechol-styrene) polymer is precipitated by spray drying to obtain the solid poly(catechol-styrene) polymer.

62. 62. The method of any one of claims 1 to 61, wherein the poly(catechol-styrene) polymer produced by the method has a molecular weight in the range of 15,000 to 1,000,000 as measured by GPC.

63. 63. The method of claim 62, wherein the poly(catechol-styrene) polymer produced by the method has a molecular weight in the range of about 50,000 to about 400,000 as measured by GPC.

64. 64. The method of any one of claims 1 to 63, wherein the poly(catechol-styrene) polymer produced by the method has a polydispersity index (PDI) of from about 1 to about 4 as measured by GPC.

65. 1. A polymerization end product comprising a poly(3,4-diacetoxystyrene-co-styrene) polymer, wherein the unconverted monomers present in the end product are less than 5% of the monomers added to the reaction mixture.

66. 66. The polymerization end product of claim 65, wherein the unconverted monomer present in the reaction mixture is less than 1% of the monomer added to the reaction mixture.

67. 66. The polymerization end product of claim 65, wherein the unconverted monomer present in the reaction mixture is less than 0.5% of the monomer added to the reaction mixture.

68. 1. A polymerization end product comprising a PCS polymer, wherein the unconverted monomers present in the reaction mixture are less than 5% of the monomers added to the reaction mixture.

69. 69. The polymerization end product of claim 68, wherein the unconverted monomer present in the reaction mixture is less than 1% of the monomer added to the reaction mixture.

70. 69. The polymerization end product of claim 68, wherein the unconverted monomer present in the reaction mixture is less than 0.5% of the monomer added to the reaction mixture.

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