WO2021121889A1

WO2021121889A1 - Dca methacrylate thermoplastic polymers

Info

Publication number: WO2021121889A1
Application number: PCT/EP2020/083404
Authority: WO
Inventors: Wouter VAN HECKE; Richard Vendamme; Karolien VANBROEKHOVEN; Pablo ORTIZ
Original assignee: Vito Nv
Priority date: 2019-12-20
Filing date: 2020-11-25
Publication date: 2021-06-24

Abstract

The present invention relates to stabilizing monomers obtained from mono(meth)acrylated monolignols providing AA (antioxidant activity) to copolymers, and obtained copolymers thereof. It further provides methods for preparing such copolymers, the building blocks and the use thereof in the manufacture of copolymers comprising said stabilizing monomers obtained from mono(meth)acrylated monolignols providing AA. In a further aspect, this invention elaborates on the possible applications of the polymers thus obtained.

Description

DCA METHACRYLATE THERMOPLASTIC POLYMERS Field of the invention

Background of the invention

Lubricants, fuels, plastics and by extension all organic matter is prone to oxidation. The process of oxidation chemically changes organic matter, possibly providing for the unwanted alteration of its properties. More specifically, sunlight, air pollution, moisture, high temperature and biological exposure among others, provide for the formation of highly reactive peroxy radicals, which interact with the organic matter and degrade it. For example, the oxidation of plastics, cause the plastic to become brittle, leading to the formation of cracks within the plastic.

Antioxidants are compounds that delay or inhibit oxidative processes, and therefore act as preserving additives and/or stabilizers, avoiding or limiting the effects of degradation. Due to the negative effect oxidation can have, antioxidants are of great importance in several industries. Antioxidants can be used in the pharmaceutical sector, the food and beverages sector, as additives in lubricants and polymer chemistry. Although there are many known natural antioxidants, the most commonly used antioxidants are synthetic, such as butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), and tert- butylhydroquinone (TBHQ).

Both synthetic and natural antioxidant compounds are widely used in food and personal care products to increase stability, shelf life and preserve nutritional quality. There has been a growing interest in the substitution of synthetic food antioxidants like butylated hydroxyl anisole (BHA) and butylated hydroxyl toluene (BHT), and in general having more antioxidant alternatives. Despite their strength, some synthetic antioxidants are known to migrate from their polymer matrix into the packaged material, which is undesirable.

Hindered phenols have been one of the most used compounds as antioxidants since the beginning. Lignin, being a polyphenolic structure is the ideal candidate for serving as a renewable, non-toxic antioxidant. Lignin works as antioxidant against the biological, chemical and mechanical stress on plants and removes potentially damaging agents, such as radicals, from a living organism. Lignin contains a huge amount of phenolic constructions, i.e. the monolignols that enable it to act as an effectual antioxidant. Also, the monomers degradation of lignin and their derivatives are known to possess high-quality antioxidant and anti-inflammatory characteristics. Additionally, besides being an anti-oxidant lignin itself has also been demonstrated to carry antimicrobial and insecticidal characteristics. Notwithstanding these interesting activities, the radical scavenging activity and hence anti-oxidant activity of lignin is greatly influenced by the complex structure of lignin in comparison to synthetic antioxidants. For example, the presence of carbonyl groups in the side chains of the polymer will have a negative effect on the anti-oxidant activity and the presence of different types of molecules like proteins, and macromolecules in the complex will have an impact on the foregoing properties of lignin. It would be interesting if one could exploit and control the beneficial effects of lignin through the synthesis of polymers derived from the monolignols whilst retaining the anti-oxidant efficiency of lignin and lignin fractions.

The biosynthesis of lignin proceeds by the radical polymerization of mainly three types of para-hydroxyl cinnamyl alcohols, commonly termed monolignols. Lignin in plants is a macromolecule with many different inter-monomer bonds, predominantly of ether nature. These bonds in lignin are broken during the depolymerization. Under harsh reaction conditions, the reactive intermediates formed will react forming carbon-carbon bonds, leading to a repolymerized, recalcitrant lignin. This lignin, with high structural variability and low solubility and compatibility, is not amenable neither for polymer synthesis nor for use as commercial antioxidants.

However, recent advances in mild depolymerization strategies allowed conversion of lignin to mixtures of monomers (up to 50%), dimers and oligomers. The most prevalent monomers found in depolymerized lignin are: propyl guaiacol (PG), propyl syringol (PS), dihydroconiferyl alcohol (DCA) and dihydrosinapyl alcohol (DSA) and the ratio of them depends on the choice of feedstock and the catalyst.

It is evident there is a need for novel polymer stabilizers having antioxidant properties. It is therefore an aim of the present invention to provide for polymer stabilizers having antioxidant properties. Further, it is an aim of the present invention to provide for polymer stabilizers which can be readily copolymerized, the copolymers obtained thereof and related method of preparations.

Summary of the invention

In a first aspect, the present invention provides stabilizing monomers obtained from mono(meth)acrylated monolignols providing AA (antioxidant activity), represented by formula V, and copolymers thereof comprising at least one monomer represented by said formula V. In particular, the present invention provides a copolymer comprising at least one monomer obtained from mono(meth)acrylated monolignols and represented by formula V

wherein;

- R₁ and R₂ each independently represent hydrogen or oxo-C_1-4alkyl; in particular hydrogen or oxo-methyl;

- A_k represents a C_1-6 carbon chain, including a C_1-6alkyl or C_1-6alkenyl;

- R₃ represents Hydrogen or C_1-6alkyl; and n is an integer ≥ 10; and at least one of R₁ or R₂ is oxo-C_1-4alkyl.

In accordance with an embodiment of the present invention, the copolymer comprises a plurality of monomers obtained from mono(meth)acrylated monolignols and represented by formula V, wherein the substituents ( R₁, R₂, A_k and R₄) are selected independently of one another.

In accordance with an embodiment of the present invention, the copolymer further comprises at least one monomer represented by formula VI

wherein;

- R₄ represent a C_1-6 carbon chain optionally substituted with aryl;

- R₅ represents Hydrogen or C_1-6alkyl; and

- Ak represents a C_1-6 carbon chain, including a C_1-6alkyl or C_1- ₆alkenyl;

- m is an integer ≥ 10. In accordance with an embodiment of the present invention, the copolymer comprises a plurality of monomers represented by formula VI, wherein the substituents (R₄, R₅, A_k and m) are selected independently of one another.

In accordance with an embodiment of the present invention, the copolymer further comprises at least one (meth)acrylic monomer, preferably selected from the group consisting of methyl methacrylates, methyl acrylates, ethyl acrylates, 2- ethylhexyl acrylate, hydroxyethyl methacrylate, butyl acrylate, butyl methacrylate, 3-phenyl-propylmethacrylate.

In accordance with an embodiment of the present invention, the copolymer is represented by formula VII

wherein;

- R₁ and R₂ each independently represent hydrogen or oxo-C_1-4alkyl; in particular hydrogen or oxo-methyl; wherein at least one of R₁ or R₂ represents oxo-C_1-4alkyl or oxo-methyl;

- A_k and A_k' each independently represents a C_1-6 carbon chain, including a Ci-6alkyl or Ci-6alkenyl;

- R₄ and R₃ each independently represents Hydrogen or Ci-6alkyl;

- R₅ and R₆ each independently represent Hydrogen or Ci-6alkyl; or R₅ and R₆ together with the carbon atom to which they are attached form a C_3-6cycloalkyl;

- R₇ represents and a C_1-6 carbon chain, optionally substituted with aryl; and n and m are each independently an integer ≥ 1.

In accordance with a further embodiment of the present invention, the copolymer represented by formula VII has substituents (R₁, R₂, A_k and R₄) and (R₇, A_k and R₈) elected independently of one another. It is also an object of the present invention to provides methods for the manufacture of the copolymers according to the invention.

In a second aspect, the present invention provides a method for the manufacture of the copolymers according to the other embodiments of the present invention.

In a further embodiment, the method comprises the step of; - contacting at least equimolar amounts of a monolignols according to formula (I) with an (meth)acrylate according to formula (II) in the presence of a lipase;

wherein; R₁ and R₂ each independently represent hydrogen or oxo-C_1-4alkyl; in particular hydrogen or oxo-methyl; wherein at least one of R₁ or R₂ represents oxo-C_1-4alkyl or oxo-methyl;

A_k represents a C_1-6 carbon chain, including a C_1-6alkyl or C_1-6alkenyl; R₃ represents a C_1-6 carbon chain, including a C_1-6alkyl or C_1-6alkenyl;

R₄ represents Hydrogen or C_1-6alkyl; yielding the mono-(meth)acrylated monolignols of formula (III).

In a further embodiment, in the method the lipase is immobilized, such as on acrylic beads.

In a further embodiment in accordance with the present invention, the method comprises the step of removing the free alcohol (IV) from the reaction mixture.

In a further embodiment in accordance with the present invention, in the method the reaction is performed in solvent-free conditions with molecular sieves or alternative methods to remove the free-alcohol from the reaction mixture.

In a further embodiment in accordance with the present invention, the step of contacting at least equimolar amounts of a monolignols according to formula (I) with an (meth)acrylate according to formula (II), is performed in the presence of a lipase and a polymerization inhibitor.

In a further embodiment in accordance with the present invention, the polymerization inhibitor is used in a concentration range of 100 to 1000 ppm of the reaction mixture. In a further embodiment in accordance with the present invention, the polymerization inhibitor is selected from 4-tert-Butylpyrocatechol; tert- Butylhydroquinone; 1,4-benzoquinone; 6-tert-Butyl-2,4-xylenol; 2-tert-Butyl-l,4- benzoquinone; 2,6-Di-tert-butyl-p-cresol; 2,6-di-tert-butylphenol; 1,1-diphenyl-2- picrylhydrazyl Free Radical; hydroquinone; 4-methoxyphenol; pPhenothiazine; more in particular 4-methoxyphenol (500 ppm) and phenothiazine (500 ppm).

In a further embodiment in accordance with the present invention, the method comprises the step of purifying the obtained mono-(meth)acrylated monolignols of formula (III) from the reaction mixture by filtering/decanting insolubles and distilling off the excess of (meth)acrylate (II).

In a further embodiment in accordance with the present invention, the method comprises the step of a radical polymerization reaction of the mono(meth)acrylated monolignols of formula (III) using a radical initiator in an appropriate solvent.

In a further embodiment in accordance with the present invention, the radical initiator is an azo compound; in particular azo compounds selected from azobisisobutyronitrile (AIBN) or 1,1'-azobis(cyclohexanecarbonitrile) (ABCN).

In a further embodiment in accordance with the present invention, the solvent is chosen from dioxane, THF, methanol, ethanol, DMF.

In a further embodiment in accordance with the present invention, the radical polymerization reaction is performed on a mixture of the mono(meth)acrylated monolignols of formula (III) with a second monomer, preferably a (meth)acrylic monomer.

In a further embodiment in accordance with the present invention, said second monomer is a (meth)acrylic monomer selected from methyl methacrylates, , methyl acrylates, ethyl acrylates, ethyl methacrylate, 2-ethylhexyl acrylate, acrylates from other Guerbet alcohols, methacrylates from Guerbet alcohols, , butyl acrylate, butyl methacrylate, propyl acrylate, propyl methacrylate, 3-phenyl- propylmethacrylate, citronellyl acrylate, geranyl acrylate, neryl acrylate, prenyl acrylate, citronellyl methacrylate, geranyl methacrylate, neryl methacrylate, prenyl methacrylate, other acrylates and methacrylates of terpene alcohols.

Brief Description of the Figures With specific reference now to the figures, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of the different embodiments of the present invention only. They are presented in the cause of providing what is believed to be the most useful and readily description of the principles and conceptual aspects of the invention. In this regard no attempt is made to show structural details of the invention in more detail than is necessary for a fundamental understanding of the invention. The description taken with the drawings making apparent to those skilled in the art how the several forms of the invention may be embodied in practice.

Figure 1, also abbreviated as Fig. 1, illustrates the antioxidant activity of ligning- derived monomers, commercial antioxidants and synthetic phenylpropanoids, more specifically, from left to right, dihydroconiferyl alcohol (DCA), propyl guaiacol (PG), dihydrosinapyl alcohol (DSA), butylated hydroxytoluene (BHT), tert- butylhydroquinone (TBHQ), hydroxypropyl di-tert-butyl phenol (HPDTBP).

Figure 2, also abbreviated as Fig. 2, illustrates IC₅₀ of poly HEMA containing lignin- derived monomers, more specifically, DCA and DSA, at various concentrations of the monomer, wherein the IC₅₀ is given in μg/mL.

Figure 3, also abbreviated as Fig. 3, illustrates the AA of m-DCA (synthetic and lignin-extracted.

Figure 4, also abbreviated as Fig. 4, illustrates the AA of synthesized copolymers.

Detailed description of the invention

The present invention will now be further described. In the following passages, different aspects of the invention are defined in more detail. Each aspect so defined may be combined with any other aspect or aspects unless clearly indicated to the contrary. In particular, any feature indicated as being preferred or advantageous may be combined with any other feature or features indicated as being preferred or advantageous. When describing the compounds of the invention, the terms used are to be construed in accordance with the following definitions, unless a context dictates otherwise. The term "about" or "approximately" as used herein when referring to a measurable value such as a parameter, an amount, a temporal duration, and the like, is meant to encompass variations of +/- 10 % or less, preferably +/- 5 % or less, more preferably +/- 1 % or less, and still more preferably +/- 0.1 % or less of and from the specified value, insofar such variations are appropriate to perform in the disclosed invention. It is to be understood that the value to which the modifier "about" or "approximately" refers is itself also specifically, and preferably, disclosed. As used in the specification and the appended claims, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise. By way of example, "a polymer" means one polymer or more than one polymer.

In the context of the present invention, by means of the term "monomer", reference is made to a single building block of a polymer, usually connected by covalent bonds to another monomer. In other words, a monomer is a basic unit of a polymer.

In the context of the present invention, by means of the term "copolymer", or "co-polymer" reference is made to polymers composed of at least two chemically different monomers. Copolymers include statistical copolymers, alternating copolymers, block copolymers, graft copolymers, and the like.

In the context of the present invention, by means of the term "monolignols", reference is made to compounds precursors of the biosynthesis of lignin, a class of polymers forming the key structural materials in e.g. plants. The term "monolignols" mainly refers to three types of para-hydroxyl cinnamyl alcohols, here below:

Monolignols Native lignin

In the context of the present invention, by means of the term "(meth)acrylic monomer", reference is made to a monomer obtained from the polymerization of a (meth)acrylic moiety. More specifically, in the context of the present invention, the term "(meth)acrylic moiety" is meant to be moieties of salts, esters and conjugate bases of (meth)acrylic acid and its derivatives, (meth)acrylates contain vinyl groups, i.e. 2 carbon atoms double bonded to each other, directly attached to a carbonyl carbon. A (meth)acrylate moiety is typically represented as follows:

wherein R represents -H in the event of acrylates or an alkyl group such as, but not limited to, methyl (-CH₃), in the event of methacrylates. The (meth)acrylate groups according to the present invention are attached to the remainder of the monomer via the -O- linker.

In the context of the present invention, by means of the term "polymerization inhibitor", reference is made to a compound which added to monomers prevents their auto-polymerization.

The present invention is directed to copolymers comprising at least one monomer obtained from mono(meth)acrylated monolignols, a method for the manufacture of copolymers in accordance with the present invention, the monomers associated and the selective (meth)acrylation of the aliphatic alcohols present in the monolignols obtainable from lignin depolymerization, and the use of the thus obtained monomers in the synthesis of poly(meth)acrylates and copolymers thereof. More specifically, in a first aspect, the present invention provides a copolymer comprising at least one monomer obtained from mono(meth)acrylated monolignols and represented by formula V

wherein;

- A_k represents a C_1-6 carbon chain, including a C_1-6alkyl or C_1-6alkenyl;

- R₃ represents Hydrogen or Ci-6alkyl; and n is an integer ≥ 10; and at least one of R₁ or R₂ is oxo-C_1-4alkyl.

The monomers represented by formula V provide for AA in copolymers comprising different monomeric mixtures and that can be obtained by means of various polymerization techniques. In other words, lignin-derived monomers of formula V can be used for making copolymers with antioxidant properties. Contrary to the standard approach of using antioxidants as additives, the monomers of formula V have been grafted to the backbone of a polymer. This has been possible by a lipase-catalyzed selective (meth)acrylation of bifunctional monomers. The selectivity of the enzymatic transformation ensures that thermoplastics are obtained. Thermosets can be obtained by addition of e.g. TMPTA, a trifunctional acrylate ester monomer. Upon copolymerization, the antioxidant activity of the monomers remains. Hence, the polymer displays interesting properties for niche applications, where antioxidant leaching needs to be avoided. In accordance with an embodiment of the present invention, R₃ is methyl.

Mixtures of monomers can be utilized in the polymerization process, some of the substituents (R₁, R₂, A_k and R₄) might be different in the repeating units. Therefore, in accordance with an embodiment of the present invention, the copolymer comprises substituents (R₁, R₂, A_k and R₄) selected independently of one another. Mixtures of different mono(meth)acrylated monolignols of formula (III) can be used, and therefore the term independently for R₁, R₂, Ak and R₄, includes any of the possible hydrogen and -oxo- C_1-4alkys in case of R₁ and R₂ and any of the possible hydrogen or C_1-6alkyl chains in case of A_k and R₄ In the following embodiments, a more detailed description of the polymers and the way of synthesizing them will be provided.

The copolymers are the result of a radical polymerization reaction of the mono(meth)acrylated monolignols of formula (III) using a radical initiator in an appropriate solvent. Solvents used in a radical polymerization reaction are known to the skilled person and required are chosen for example from dioxane, THF, methanol, ethanol, DMF and others. In a preferred embodiment the radical polymerization reaction is performed by dissolving the mono(meth)acrylated monolignols of formula (III) in dioxane and initiating the reaction by adding a radical initiator such as AIBN, ABCN or other preferably carbon-centered radicals.

wherein;

- R₄ represent a C_1-6 carbon chain optionally substituted with aryl;

- R₅ represents Hydrogen or C_1-6alkyl; and - Ak represents a C_1-6 carbon chain, including a C_1-6alkyl or C_1- ₆alkenyl;

- m is an integer ≥ 10.

In the context of the present invention, by means of the term "radical initiator", reference is made to one or more compounds promoting radical reactions by producing radical species. These substances generally possess weak bonds— bonds that have small bond dissociation energies. Typical examples are generally known to the person skilled in the art and include halogen molecules, azo compounds, and organic and inorganic peroxides. Within the context of the present invention azo compounds are preferably being used as radical initiators since they provide two carbon-centered radicals and nitrogen gas which is easily separated from the reaction mixture. In a particular embodiment the radical initiators used in the radical polymerization reaction according to the invention are azo compounds selected from azobisisobutyronitrile (AIBN) or 1,1'- azobis(cyclohexanecarbonitrile) (ABCN). It has been reported in a literature before that lignin compounds can slow down or inhibit radical polymerization and this effect is more pronounced in the case of oxygen centered rather than carbon centered radical initiators where polymerization using peroxide initiators can be stopped completely even by additions of small amounts of eugenol.

Hence, in accordance with an embodiment of the present invention, the copolymers can be represented by formula VII

wherein;

- A_k and A_k' each independently represents a C_1-6 carbon chain, including a C_1-6alkyl or C_1-6alkenyl;

- R4 and R₃ each independently represents Hydrogen or C_1-6alkyl; - R₅ and R₆ each independently represent Hydrogen or C_1-6alkyl; or R₅ and R6 together with the carbon atom to which they are attached form a C_3-6cycloalkyl;

In accordance with an embodiment of the present invention, the copolymer comprises the mono-(meth)acrylated lignin-based monomers of formula (III) together with other (meth)acrylic monomers such as for example methyl methacrylates, , methyl acrylates, ethyl acrylates, ethyl methacrylate, 2- ethylhexyl acrylate, acrylates from other Guerbet alcohols, methacrylates from Guerbet alcohols, , butyl acrylate, butyl methacrylate,, propyl acrylate, propyl methacrylate, 3-phenyl-propylmethacrylate, citronellyl acrylate, geranyl acrylate, neryl acrylate, prenyl acrylate, citronellyl methacrylate, geranyl methacrylate, neryl methacrylate, prenyl methacrylate, other acrylates and methacrylates of terpene alcohols and the like.

In accordance with a preferred embodiment of the present invention, the copolymer further comprises at least one (meth)acrylic monomer, preferably selected from the group consisting of methyl methacrylates, methyl acrylates, ethyl acrylates, 2-ethylhexyl acrylate, hydroxyethyl methacrylate, butyl acrylate, butyl methacrylate, 3-phenyl-propylmethacrylate.

In accordance with a further embodiment of the present invention, the copolymer represented by formula VII has substituents (R₁, R₂, A_k and R₄) and (R₇, A_k and R₈) elected independently of one another.

To the best of our knowledge, polymers of mono-(meth)acrylated monolignols, such as dihydroconiferyl alcohol (DCA) mono(meth)acrylate polymers have not been described before. The objective of the current patent application is to protect the product, i.e. copolymers of such monomers like dihydroconiferyl mono(meth)acrylates and derived polymers (e.g. where aromatic hydroxyl group is esterified).

Besides DCA (represented below), lignin oil is known to comprise further coniferyl alcohols. Some of them reproduced below, but a general overview of the alcohols that can be found in such oils can generally be represented according to formula (I).

(I) wherein;

R₁ and R₂ each independently represent Hydrogen, Hydroxy, Aryl or -oxo-C_1-4alkyl; in particular Hydrogen, hydroxy or -oxo- Methyl;

Ak represents a C_1-6 carbon chain, including a C_1-6alkyl or C_1-6alkenyl

The term "alkyl" by itself or as part of another substituent refers to a fully saturated hydrocarbon of Formula CxH2x+l wherein x is a number greater than or equal to 1. Generally, alkyl groups of this invention comprise from 1 to 20 carbon atoms. Alkyl groups may be linear or branched and may be substituted as indicated herein. When a subscript is used herein following a carbon atom, the subscript refers to the number of carbon atoms that the named group may contain. Thus, for example, C_1-4alkyl means an alkyl of one to four carbon atoms. Examples of alkyl groups are methyl, ethyl, n-propyl, i-propyl, butyl, and its isomers (e.g. n-butyl, i-butyl and t-butyl); pentyl and its isomers, hexyl and its isomers, heptyl and its isomers, octyl and its isomers, nonyl and its isomers; decyl and its isomers. C_1-6alkyl includes all linear, branched, or cyclic alkyl groups with between 1 and 6 carbon atoms, and thus includes methyl, ethyl, n-propyl, i- propyl, butyl and its isomers (e.g. n-butyl, i-butyl and t-butyl); pentyl and its isomers, hexyl and its isomers, cyclopentyl, 2-, 3-, or 4-methylcyclopentyl, cyclopentylmethylene, and cyclohexyl.

The term "alkenyl", as used herein, unless otherwise indicated, means straight- chain, cyclic, or branched-chain hydrocarbon radicals containing at least one carbon-carbon double bond. Examples of alkenyl radicals include ethenyl, E- and Z-propenyl, isopropenyl, E- and Z-butenyl, E- and Z-isobutenyl, E- and Z-pentenyl, E- and Z-hexenyl, E,E-, E,Z-, Z,E-, Z,Z-hexadienyl, and the like. An optionally substituted alkenyl refers to an alkenyl having optionally one or more substituents (for example 1, 2, 3 or 4), selected from those defined above for substituted alkyl.

The term "aryl" as used herein refers to a polyunsaturated, aromatic hydrocarbyl group having a single ring (i.e. phenyl) or multiple aromatic rings fused together (e.g. naphthalene or anthracene) or linked covalently, typically containing 6 to 10 atoms; wherein at least one ring is aromatic. The aromatic ring may optionally include one to three additional rings (either cycloalkyl, heterocyclyl, or heteroaryl) fused thereto. Aryl is also intended to include the partially hydrogenated derivatives of the carbocyclic systems enumerated herein. Non-limiting examples of aryl comprise phenyl, biphenylyl, biphenylenyl, 5- or 6-tetralinyl, 1-, 2-, 3-, 4-, 5-, 6-, 7-, or 8-azulenyl, 1- or 2-naphthyl, 1-, 2-, or 3-indenyl, 1-, 2-, or 9-anthryl, 1- 2-, 3-, 4-, or 5-acenaphtylenyl, 3-, 4-, or 5-acenaphtenyl, 1-, 2-, 3-, 4-, or 10- phenanthryl, 1- or 2-pentalenyl, 1, 2-, 3-, or 4-fluorenyl, 4- or 5-indanyl, 5-, 6-, 7-, or 8-tetrahydronaphthyl, 1,2,3,4-tetrahydronaphthyl, 1,4-dihydronaphthyl, dibenzo[a,d]cylcoheptenyl, and 1-, 2-, 3-, 4-, or 5-pyrenyl.

The aryl ring can optionally be substituted by one or more substituents. An "optionally substituted aryl" refers to an aryl having optionally one or more substituents (for example 1 to 5 substituents, for example 1, 2, 3 or 4) at any available point of attachment. Non-limiting examples of such substituents are selected from halogen, hydroxyl, oxo, nitro, amino, hydrazine, aminocarbonyl, azido, cyano, alkyl, cycloalkyl, alkenyl, alkynyl, cycloalkylalkyl, alkylamino, alkoxy, -S02-NH2, aryl, heteroaryl, aralkyl, haloalkyl, haloalkoxy, alkoxycarbonyl, alkylaminocarbonyl, heteroarylalkyl, alkylsulfonamide, heterocyclyl, alkylcarbonylaminoalkyl, aryloxy, alkylcarbonyl, acyl, arylcarbonyl, aminocarbonyl, alkylsulfoxide, -S02Ra, alkylthio, carboxyl, and the like, wherein Ra is alkyl or cycloalkyl.

Within the context of the present invention all of said coniferyl alcohols of formula (I) could serve as reagents in the selective (meth)acrylation of the aliphatic alcohols present in said coniferyl alcohols, and the use thereof in the synthesis of copolymers. As will be further detailed below, such selective (meth)acrylation followed by polymerization yields products that are not necessarily irreversibly crosslinked.

It is accordingly an object of the present invention to provide copolymers of the aliphatic (meth)acrylates of the coniferyl alcohols found in lignin oil and represented by formula (I) above, in particular (meth)acrylates of DCA and of the following alcohols as we expect them to be present in the lignin oil as well: p-Coumaryl alcohol Coniferyl alcohol Sinapyl alcohol

dihydroconiferyl alcohol (DCA)

Several different monomers can be obtained from wood deconstruction using different techniques and the aforementioned monolignols, including the reduced products like dihydroconiferyl alcohol are one of them. As mentioned above, all of the coniferyl alcohols, and in particular the reduced monolignols obtainable from lignin depolymerization can be used in the selective (meth)acrylation of the aliphatic alcohols and serve as building blocks in the subsequent polymerisation reaction.

(Meth)acrylate polymers are currently produced at large scale for a number of applications. The most common large scale methods to prepare (meth)acrylic monomers include reaction with (meth)acrylic anhydrides or chlorides, however, in the case of dihydroconiferyl alcohols the conventional methods would likely lead to (meth)acrylation of the aliphatic and the aromatic hydroxyl group, leading to high degree of crosslinking if no extensive purification is applied.

As it was our ambition to prepare polymers with a low degree of crosslinking, we needed (meth)acrylic monomers with a selective (meth)acrylation of the aliphatic hydroxyl group, preferably without protecting the aromatic hydroxyl group as this would lead to inefficient synthesis. In the method of the present invention this is achieved by the use of a lipase. We know from previous work that lipases (Novozyme 435) cannot esterify aromatic hydroxyl groups, but readily esterify aliphatic hydroxyl groups (Heeres et al., 2019).

In the context of the present invention, by means of the term "lipase", reference is made to an enzyme that catalyzes the hydrolysis of esters. Further examples of lipases are Lipozyme^® CALB from Candida Antartica B, Novocor^® AD L from Candida Antartica A, Lipozyme^® TL 100 L from Thermomyces lanuginose, Resinase^® HT from Aspergillus oryzae, Palatase^® 20000 L from Rhizomucour miehei and Novozym^® 51032 from Humicola insolens.

The utilization of lipase for selective esterification of an aliphatic hydroxyl group while leaving the aromatic hydroxyl group untouched can also be found in work from Uyama and Kobayashi (2006) where artificial urushi was used using a lipase and laccase catalyzed step, see below. In the enzymatic synthesis of artificial urushi: lipases are used to esterify the aliphatic hydroxyl group, while the aromatic hydroxyl group remains untouched.

In this study, 4-hydroxymethylcatechol was used as an alcohol instead of DCA. However, the selective (meth)acrylation of the aliphatic alcohols of the monolignols obtainable from lignin depolymerization has never been disclosed before.

Where this method effectively yields a predominant selective (meth)acrylation of the aliphatic alcohols, it cannot be excluded that given the presence of unprotected aromatic hydroxyl groups in the alcohols that can be found in such lignin oils, that some of these could also get (meth)acrylated, which in the subsequent polymerization reaction could lead to a low degree of crosslinking. It is also an object of the present invention to provides methods for the manufacture of the copolymers according to the invention.

(I) (II) (III) (IV) wherein; R₁ and R₂ each independently represent hydrogen or oxo-C_1-4alkyl; in particular hydrogen or oxo-methyl; wherein at least one of R₁ or R₂ represents oxo-C_1-4alkyl or oxo-methyl;

A_k represents a C_1-6 carbon chain, including a C_1-6alkyl or C_1-6alkenyl; R₃ represents a C_1-6 carbon chain, including a Ci-6alkyl or C_1-6alkenyl;

R₄ represents Hydrogen or Ci-6alkyl; yielding the mono-(meth)acrylated monolignols of formula (III).

In a further embodiment, in the method the lipase is immobilized, such as on acrylic beads. It has been observed that for the selective (meth)acrylation of the aliphatic alcohols best yields (>90%) are achieved in case the free alcohol (IV) is removed from the reaction mixture. Hence, in a further embodiment in accordance with the present invention, the method comprises the step of removing the free alcohol (IV) from the reaction mixture.

Said techniques in removing the free-alcohol (IV) from the reaction mixture could equally be performed in preconditioning the reagents, as it has been established that the efficiency in the selective (meth)acrylation of the aliphatic alcohols of the monolignols, could be further increased when performed in dehydrating conditions, i.e. in employing anhydrous reagents. Common desiccants include phosphorus pentoxide and silica gel, can be used to store the solid reagents in dry conditions and for the liquid reagents the aforementioned molecular sieves or alternative methods to remove the water from the liquid reagents. In an embodiment the reaction is performed in dehydrating conditions, preferably in combination means with molecular sieves to remove the free-alcohol from the reaction mixture.

In an exemplified embodiment the lipase is Novozyme 435 immobilized on acrylic beads, present in an amount of about 10 wt% with respect to the initial total mass of substrates, wherein the initial amount of the (meth)acrylate is used in a molar excess when compared to the monolignol, in particular the initial molar excess ratio of the (meth)acrylate to the monolignol is from between and about 1 to 4; more in particular the initial molar excess ratio of the (meth)acrylate to the monolignol is about 3.

In the foregoing reaction the reaction mixture is typically kept between 30 and 80°C for a time sufficient to ensure near complete conversion of the alcohols. For example in case of DCA with methyl(meth)acrylate the reaction mixture is kept at 60°C, with a residence time of 48-65h to ensure complete conversion for all alcohols.

Since poly(meth)acrylates are produced by means of free radical polymerization, and can even be polymerized at moderate temperatures even without the need of adding a radical initiator, an uncontrolled polymerization reaction could start as the concentration of the mono-(meth)acrylated monolignols of formula (III) increases in the reaction mixture. Hence, in this transesterification reaction polymerization inhibitors are always preferably added to the reaction mixture. Within the context of the present invention the art known polymerization inhibitors can be used in a concentration range of 100 to 1000 ppm of the reaction mixture, in particular of about 500 ppm. Polymerization inhibitors such as 4- methoxyphenol (100-1000 ppm), hydroquinone (100-1000 ppm), 2,4-Dimethyl-6- tertbutylphenol (100-1000 ppm), phenothiazine (100-1000 ppm) and the like. Thus, in a further embodiment in accordance with the present invention, the step of contacting at least equimolar amounts of a monolignols according to formula (I) with an (meth)acrylate according to formula (II), is performed in the presence of a lipase and a polymerization inhibitor. Hence, from the above, in a further embodiment in accordance with the present invention, the polymerization inhibitor is used in a concentration range of 100 to 1000 ppm of the reaction mixture.

In a further embodiment in accordance with the present invention, the polymerization inhibitor is selected from 4-tert-Butylpyrocatechol; tert- Butylhydroquinone; 1,4-benzoquinone; 6-tert-Butyl-2,4-xylenol; 2-tert-Butyl-l,4- benzoquinone; 2,6-Di-tert-butyl-p-cresol; 2,6-di-tert-butylphenol; 1,1-diphenyl-2- picrylhydrazyl Free Radical; hydroquinone; 4-methoxyphenol; pPhenothiazine; more in particular 4-methoxyphenol (500 ppm) and phenothiazine (500 ppm).

The mono-(meth)acrylated monolignols of formula (III) obtained using the selective (meth)acrylation method of the present invention can simply be purified from the reaction mixture by filtering/decanting insolubles and distilling off the excess of (meth)acrylate (II) used in the synthesis of the mono-(meth)acrylated monolignols of formula (III). As already mentioned herein before, these mono- (meth)acrylated monolignols of formula (III) are characterized in retaining the aromatic alcohols known to provide lignin amongst others its antioxidant and anti- inflammatory characteristics. Within lignin these aromatic alcohols act as radical scavengers and accordingly protect plants against the biological, chemical and mechanical stress by removing potentially damaging agents. Being radical scavengers it was not to be expected that these mono-(meth)acrylated monolignols of formula (III) could be used efficiently as monomers in the radical polymerization reaction. Still, the mono-(meth)acrylated monolignols of formula (III) could be used as monomers in radical polymerization reaction using AIBN (or potentially other initiators) in dioxane (or potentially other solvents) without any further purification. Hence, in a further embodiment in accordance with the present invention, the method comprises the step of purifying the obtained mono-(meth)acrylated monolignols of formula (III) from the reaction mixture by filtering/decanting insolubles and distilling off the excess of (meth)acrylate (II).

In a further embodiment in accordance with the present invention, the radical polymerization reaction is performed on a mixture of the mono(meth)acrylated monolignols of formula (III) with a second monomer, preferably a (meth)acrylic monomer. In a further embodiment in accordance with the present invention, said second monomer is a (meth)acrylic monomer selected from methyl methacrylates, , methyl acrylates, ethyl acrylates, ethyl methacrylate, 2-ethylhexyl acrylate, acrylates from other Guerbet alcohols, methacrylates from Guerbet alcohols, , butyl acrylate, butyl methacrylate, propyl acrylate, propyl methacrylate, 3-phenyl- propylmethacrylate, citronellyl acrylate, geranyl acrylate, neryl acrylate, prenyl acrylate, citronellyl methacrylate, geranyl methacrylate, neryl methacrylate, prenyl methacrylate, other acrylates and methacrylates of terpene alcohols.

The synthesis of the copolymers in accordance with the present invention will become apparent from the specific examples provided herein below.

Examples

It is known that lignin-derived monomers have antioxidant activity (AA) due to the presence of phenolic OH groups. However, until now, the exploitation of the antioxidant activity of lignin in polymer chemistry has been mainly limited to using it as an additive in thermoplastic polymers. Besides, thermosets containing lignin have also been assessed for their antioxidant activity, but the incorporation of discrete lignin-derived monomers into a polymer to confer to it antioxidant activity has remained largely unexplored. It has been an objective of the present invention to synthesize novel anti-oxidative poly(meth)acrylates that could find niche applications as e.g. anti-oxidative water proofing agent in skin care products and as anti-oxidative hydrogels for wound healing applications. To this end, and as further detailed herein below, a two-step process was established. In a first step, the monomer was enzymatically produced in solvent less conditions ensuring a selective (meth)acrylation of the aliphatic hydroxyl group (and not of the aromatic hydroxyl group) using an immobilized lipase. In a second step, the obtained monomers were copolymerized using a free radical polymerization strategy.

Materials and methods

Materials

Depolymerized pine lignin oil was kindly provided by Bert Sels from the Center for Sustainable Catalysis and Engineering (KULeuven, Belgium). Dihydrosinapic acid was kindly provided by Avans University of Applied Sciences (The Netherlands). Butanediol monoacrylate (BDMA) was kindly provided by BASF (Ludwigshafen, Germany). The rest of the products were purchased from commercial sources: Dihydroeugenol (99+%, Sigma-Aldrich, Schnelldorf, Germany); Lithium aluminium hydride (Alfa Aesar, 97%); Borane dimethylsulfide complex (Alfa Aesar, Massachusetts, USA); Hydrogen peroxide (Fisher BioReagents, 30 wt% in water); Hydrochloric acid (Fisher Chemical, 37 wt%); Sodium hydroxide (Acros Organics, >99.9%) Magnesium sulfate (Acros Organics, 97%); Diethyl ether (Fisher Chemical, >99%); Silica gel pore size 60Å, 230-400 mesh particles and 40-63 μm particle size; Carbon disulfide (Acros Organics, 99.9%); Ethyl acetate (Alfa Aesar, 99%); Methanol (MeOH, Fisher Chemical, 99.9%, degassed with N2 prior to use in the DPPH test); Tetrahydrofuran (THF, Acros Organics, 99+%, dried using molecular sieves (3Å)); Dichloromethane (DCM, Acros Organics, 99.6%) 2,2-diphenyl-l- (2,4,6-trinitrophenyl)-hydrazinyl (DPPH, Cayman Chemicals ≥95,0%) 3,5-Di-tert- butylhydroxytoluene (BHT, Supelco, ≥95,0%); Tert-Butylhydroquinone (TBHQ, Acros Organics, 97%); 2-(4-Hydroxyphenyl)ethanol (HPE, Acros Organics, 98%); Methyl methacrylate (MMA, Alfa Aesar, 99%); Methyl acrylate (MA, Alfa Aesar, 99%); 3,5-di-tert-butyl-4-hydroxyphenylpropionic acid (Alfa Aesar, 98%); Trimethylolpropane triacrylate (Alfa Aesar) Hydroxy ethyl methacrylate (HEMA, Alfa Aesar, 97%); 4-methoxyphenol (MEHQ, Sigma Aldrich, 99%); Phenothiazine (Sigma Aldrich, 98%); Novozym 435 (Sigma Aldrich), Molecular Sieves 5A (Sigma Aldrich); Azobisisobutyronitrile (AIBN, Sigma Aldrich, 98%); 1-Methyl imidazole (Alfa Aesar, 99%).

Methods

Proton nuclear magnetic resonance (¹H) spectra were obtained using a 400 MHz Bruker spectrometer. Chemical shifts (δ) were recorded in ppm relative to the residual signal of the deuterated solvents. Coupling constants (J) are reported in Hertz (Hz) Multiplicities are reported as follows: s, singlet; d, doublet; t, triplet; q, quartet; quint, quintuplet; m, multiplet; br, broad.

Possible thermal phase transitions in all of the cured resin specimens were investigated using differential scanning calorimetry (DSC). The measurements were conducted with TA Discovery DSC 250 by subjecting the samples to a heat-cool-heat cycle from -70 to 200 °C at 10 °C/min rate. Normalized heat flows were plotted as a function of temperature, and the plots were analyzed. The glass transition temperature (T_g) was defined as the half value of the heat capacity change (ΔCp/2).

Gel permeation chromatography (GPC) was performed on a Styragel HR1 column eluting with tetrahydrofuran with RID detection.

The antioxidant activity was determined by the free radical scavenging activity test using 2,2-diphenyl-1-picrylhydrazyl radical (DPPH), as reported in the literature (Sharma, O. P, et al. 2009; Faustino H., et al. 2010; Scherer R., et al., 2009). A 200 μmol/L stock solution of DPPH was prepared in methanol and was stored in the dark under N2 atmosphere at 4°C. A calibration curve was formed by measuring the UV absorbance of a DPPH solution in methanol at a concentration range from 5 to 200 μmol/L. Stock solutions of 1000 μg/mL were prepared of each monomer in methanol, and then diluted to prepare samples with different concentrations. 1,0 mL of these samples were mixed with DPPH (200 μmol/L, 0,5 mL) and 0,5 mL methanol in 2 mL Eppendorf tubes. The end concentrations in the tubes were 5, 10, 20, 50, 100 and 200 μg/mL of the monomer samples and 50 μmol/L (19,72 μg/mL) of DPPH. After incubating the mixtures for 30 minutes at room temperature in the dark, the absorbance was measured in triplicate at wavelength 517 using Perkin Elmer Lambda 365 UV-VIS Spectrophotometer. The Inhibition percentage (1%) was calculated according to the following formula: 100

where Abs_sample is the measured absorption of the samples with antioxidants, Abs_blank is the blank with only methanol and the Abs_standard is the absorbance of the DPPH in the absence of sample. The start concentration of the antioxidant was plotted against the 1%. The IC₅₀ values (μg/mL) were calculated graphically using the obtained curve in the linear range. IC₅₀ stands for Inhibitory Concentration and it is the concentration of antioxidant at 50% of inhibition. The antioxidant activity is also expressed as Antioxidant Activity Index (AAI) which was calculated via the this formula:

This index provides values independent of DPPH and sample concentration. The data are mean ± SD.

The same method was used for polymers with the following modifications. All polymers were grinded to reduce their particle size and facilitate dissolution. Further, they were sonicated for 15 min using Ultrasonic Silvercrest SUR 46A150 Hz. This ensured maximum solubility of the polymer in methanol. The thermoset, due to its cross-linked nature did not dissolve, and it was measured as a suspension. H PE (10-500 μg/mL) and HEM A with 1% M-DCA ( 100- 1500 μg/mL) have different end concentrations due to their lower antioxidant activity.

Synthesis

Monomer Synthesis

Synthesis of Dihydroconiferyl alcohol (DCA)

The synthesis of dihydroconiferyl alcohol involves hydroxylation of the double bond of eugenol using an anti-Markovnikov addition. This is a two-step reaction, modified from Pepper et al., 1971, with safety advices incorporated from Atkins et al., 2006.

First step: Dry a three-neck round bottom flask in the oven and add eugenol to it. Fit a dropping funnel, a calcium chloride drying tube and an inlet for nitrogen. Then add dry tetrahydrofuran (previously dried over molecular sieves). Cool the reaction media to 0°C using an ice bath. Add the borane dimethyl sulfide complex dropwise (5 minutes). Remove from the ice bath and stir for 55 minutes. Remove the drying tube and the funnel. Carefully add water: tetrahydrofuran (1:1) mixture to destroy the excess borane.

Second step: Cool down the mixture to 0°C using an ice bath. Add aqueous NaOH solution, allow to warm up to room temperature and then carefully add 30% H₂O₂ while having nitrogen flow. Stir for one hour. Extract the resulting pale yellow solution with diethyl ether, saturate it with NaCI, acidify it with HCI and extract it again with ether. Combine and concentrate the ether layers.

Purification: To a round-bottom or erlenmeyer flask, add 200 mL of 1:5 mixture of DCM:Petroleum Ether or 1 : 6 mixture of chloroform : carbon disulfide. Gently warm the mixture in 40 °C water bath until everything is dissolved. If the product is not all dissolved then add more solvent and use minimum amount of solvent that dissolves the product at 40 °C. Cool down the mixture till room temperature, then put it in a fridge and keep for 1 h. Put the mixture in -20 °C freezer. Collect the product by vacuum filtration. Colorless crystals were obtained in 73% yield and 95% isomer purity. 1H NMR (600 MHz, CDCI3) δ 6.83 (d, J = 7.9 Hz, 1H), 6.72 - 6.67 (m, 2H), 3.87 (s, 3H), 3.68 (t, J = 6.4 Hz, 2H), 2.64 (t, J = 7.6 Hz, 2H), 1.87 (tt, J = 7.6, 6.4 Hz, 2H).

Besides chemical synthesis DCA was equally extracted from depolymerized lignin oil. Depolymerized pine lignin oil from pine was received from the Center for Sustainable Catalysis and Engineering (KULeuven, Belgium) with the following specifications: 24.9 wt% of monomers, out of which 22.3% corresponded to DCA. The DCA was extracted from the lignin oil mixture according to the following protocol. First, the methanol in which the lignin oil was dissolved was evaporated under reduced pressure. After, the lignin oil was fractionated using Et₂O. 10 grams of lignin oil were added to 100 ml of diethyl ether and refluxed for 16-20h. The solution was filtered through a Whatman filter paper and the solvent evaporated. The Et₂O soluble fraction accounted for 75-85% of the weight and it was obtained as dark orange viscous liquid. The Et₂O insoluble fraction accounted for 15-25% of the weight and it was obtained as a powder. The Et₂O soluble fraction was further extracted with water. 8 grams of the Et₂O soluble fraction was added to 80 ml of water and stirred at 40°C for 30 min. Then it was let to cool and settle down and the water collected after filtering through a Whatman filter paper. The protocol was repeated two more times, the second one heating at 70°C for lh and the third one at reflux for 2h. The combined water was evaporated under reduced pressure to give 3.1 grams of yellow oil. The oil contained mainly DCA, together with some DCA dimers and some other compounds in small amount, as inferred by 1H NMR. 1.9 grams of pure DCA could be isolated by column chromatography (Silica gel, AcOEt: Hexane 1:2→ 2:1)

Synthesis of Dihydrosinapyl alcohol (PSA)

Under anhydrous atmosphere dihydrosinapic acid (8 gram, 35 mmol) was dissolved in anhydrous THF and cooled down to 0°C. Lithium aluminum hydride (3.00 gram, 79 mmol) was added portionwise over 1 hour. The reaction mixture was stirred at room temperature overnight. The reaction was quenched by slowly pouring it into ethyl acetate, followed by the addition of water. The aqueous layer was extracted with ethyl acetate, the organic layers were combined and washed using brine. The solvent was dried using magnesium sulfate, filtered and removed in vacuo. The product was obtained as yellow liquid in 91% yield. 1H NMR (400 MHz, CDCI3) δ 6.42 (s, J = 3.8 Hz, 2H), 3.86 (s, J = 6.2 Hz, 6H), 3.67 (t, J = 6.4 Hz, 2H), 2.63 (t, J = 7.5 Hz, 2H), 1.87 (tt, J = 7.6, 6.4 Hz, 2H).

Synthesis of 2,6-di-tert-butyl-4-(3-hvdroxypropyl)phenol

Under anhydrous atmosphere 3,5-di-tert-butyl-4-hydroxyphenylpropionic acid (2.45 gram, 9 mmol) was dissolved in anhydrous THF and cooled down to 0°C. Lithium aluminum hydride (0.73 gram, 19 mmol) was added portionwise over 1 hour. The reaction mixture was stirred at room temperature overnight. The reaction was quenched by slowly pouring it into ethyl acetate, followed by the addition of water. The aqueous layer was extracted with ethyl acetate, the organic layers were combined and washed using brine. The solvent was dried using magnesium sulphate, filtered and removed in vacuo. The product was obtained as yellow oil in 88% yield and precipitated into a white powder after drying it further in the oven.

Synthesis of (methyl)acrylated DCA

1.82 grams of DCA (10 mmol) and 156 pL of 1-MI (5 mol % to the methacrylic anhydride content) was added to a 50 ml three neck round bottom flask and was dried using a nitrogen flow for 15 minutes. Then 5.92 mL of methacrylic anhydride (40 mmol) was and the reaction was stirred for 24 hours on 80 °C. After, 50 mL of DCM was added to the mixture and the reaction was washed with 3x100 mL saturated NaHCC>3, followed by 100 mL 1M HCI and finally 100 mL of water.

1H NMR (600 MHz, Chloroform) δ 6.96 (s, 1H, H7), 6.80 -

6.74 (m, 2H, H6, H8), 6.33 (dd, 2.3, 1.1 Hz, 1H, H10), 6.10 (dd, J = 2.1, 1.0 Hz, 1H, H2), 5.72 (dd, J = 1.9, 1.6 Hz, 1H, H2), 5.56 (dd, J = 2.1, 1.6 Hz, 1H,H10), 4.18 (t, J = 6.5, 1.5 Hz, 2H, H3), 3.79 (s, 3H, H9), 2.70 (t, J = 7.6, 1.4 Hz, 2H, H5), 2.08 - 2.04 (dd, 1.7, 1.1 Hz 3H, Hll), 2.04 - 1.97 (m, 3H, H4), 1.95 (dd, J = 1.6, 1.0 Hz, 3H, HI).

Selective Transesterification

Novozym 435 (immobilized on acrylic beads) was used as catalyst for all transesterification at 60°C of the non-(methyl)acrylated monomers mentioned above. Detailed (solventless) reaction conditions are described by Heeres et al., 2019. In these tests, the lipase quantity was always 10 (wt/wt)% with respect to the initial total mass of substrates and the initial molar ratio was always 3 [methyl(meth)acrylate] to 1 (alcohol). Desiccants (Molecular Sieve UOP Type 5Å, Sigma-Aldrich, Schnelldorf, Germany) were used to remove methanol and to allow complete conversion of the (high-boiling) alcohol. The residence time was 48-65h to ensure complete conversion for all alcohols. 4-methoxyphenol (500 ppm) and phenothiazine (500 ppm) are always added as polymerization inhibitors.

Said Selective transesterification reaction yielded the following (meth)acrylated monomers:

Methacrylated dihydroconiferyl alcohol (M-DCA) ¹H NMR (400 MHz): δ 6.82 (d, J = 8.5, 1H, H₇), δ 6.69 - 6.65 (m, 2H, H₆, H₈), 6.10 (dd, J = 1.8, 0.9 Hz, 1H, H₁), δ 5.56 (dd, J = 1.6, 0.7 Hz, 1H, H₁), δ 4.15 (t, J = 6.5, 0.7 Hz, 2H, H₃), 3.86 (s, 3H, H_g), 2.63 (t, J = 6.8 Hz, 2H, H_s), 2.01 - 1.96 (m, 1H, H₄), 1.94 (dd, J = 1.6, 0.8 Hz, 3H, H₂). iferyl alcohol (A-DCA)

¹H NMR (400 MHz): 6.82 (d, J = 8.5 Hz, 1H, H₇), 6.71 - 6.62 (m, 2H, H₆, H₈), 6.40 (ddd, J = 17.3, 1.5, 0.5 Hz, 1H, H₁), δ6.13 (ddd, J = 17.3, 10.4, 0.5 Hz, 1H, H₂), 5.82 (ddd, J = 10.4, 1.4, 0.5 Hz, 1H, H₁), 4.17 (t, J = 6.5 Hz, 2H, H₃), 3.85 (s, 3H, H_g), 2.63 (t, J = 8.6, 6.8 Hz, 2H, H₅), 2.02 - 1.90 (m,

2H, H₄).

Methacrylated dihydrosinapyl alcohol (M-DSA)

¹H NMR (400 MHz): δ 6.36 (s, 2H, H₆), 6.07 (dd, J = 2.0, 1.0 Hz, 1H, H₂) 5.52 (dd, J = 4.9, 1.6 Hz, 1H, H₂), 5.44 (s, 1H, H₈), 4.13 (t, J = 6.5 Hz, 2H, H₃), 3.82 (s, 6H, H₇), 2.60 (t, J = 8.5, 6.7 Hz, 2H, H_s), 1.99 - 1.94 (m, 2H, H₄), 61.92 (dd, J = 1.6, 1.0 Hz, 3H, H₁).

Methacrylated hydroxypropyl di-tert-butyl phenol (M-

HPDTBP) ¹H NMR (400 MHz) δ 6.96 (s, 2H, H₆), 6.09 (dd, J = 2.0, 1.0 Hz, 1H, H₂), 5.54 (dd, J = 1.6 Hz, 1H, H₂), 5.04 (s, 1H, H₈), 4.16 (t, J = 6.5 Hz, 2H, H₃), 2.68 - 2.55 (t, 2H, H₅), 2.01 - 1.96 (m, 2H, H₄), 1.94 (s, 2H, H₁), 1.41 (s, 18H, H₇).

Polymerization

First series of radical polymerization reactions Solvents were degassed for at least 15 minutes before use.

To a small scintillation vial (20 mL), capped with two septa were added:

1 - 1.0 g of monomer or mixture of monomers.

2 - 2 mL of dioxane.

3 - AIBN solution in dioxane was then added via syringe through septa.

4 - Mixture was additionally degassed for 10 min. and heated at 75°C oil bath for 20h.

5 - Vials then were opened to air and purified twice by dissolving in minimum amount of DCM and precipitating into 100 mL of ice-cold diethyl ether.

6 - Polymers were dried in a vacuum oven overnight (40 °C).

A set of homopolymers and copolymers with 3-phenyl-propylmethacrylate has been obtained:

Monomer feed (mass composition):

R³ and R⁴ are methyl

R⁵ and R⁶ are methyl

Second series of radical polymerization reactions In a further series the (meth)acrylated lignin-derived monomers were copolymerized with other monomers: methyl methacrylate (MMA), hydroxyethyl methacrylate (HEMA) and 1,4-butanediol monoacrylate (BDMA)

n = 1 HEMA

DCA: R¹ = H n = 3 BDMA DSA: R¹ = OMe

Initially, bulk polymerization was attempted, but the uncontrolled results led us to perform the reaction in solvent.

The (co)polymerization was performed by refluxing, under nitrogen atmosphere, the (co)monomers in 500 wt.% AcOEt and 1 wt.% AIBN. The AcOET was evaporated in the rotary evaporator and the (co)polymer was dried in the oven under 80°C for three hours.

The thermoset material was synthesized under solventless conditions with 1 wt.% trimethylolpropane triacrylate, 90 wt.% HEMA, 10 wt.% acrylated dihydroconiferyl alcohol and 1 wt.% AIBN. The reaction was performed under nitrogen and 120°C.

Polymers were characterized by DSC, GPC and ¹H NMR.

Results

Monomers

It is known that lignin-derived monomers have antioxidant activity (AA) due to the presence of phenolic OH groups. Other elements of their structure determine the extent of the AA. DCA and DSA were the monomers of interest for further functionalization, and their activity was measured and compared with benchmarks and similar compounds to gain insight into structure-property relationships, see Fig. 1. The AA was determined by the DPPH assay, the most commonly used test, and the results usually expressed as IC₅₀. This stands for Inhibitory Concentration and it is the concentration of antioxidant at 50% of inhibition. The AA of the monomers expressed as IC₅₀ and the standard deviation (SD) can be seen in Table 1.

Table 1

The IC₅₀ value of DCA was determined to be 28.8 μM, in line with previous data. This value is higher than that of PG, which showed a value of 16.2 μM. The lower activity of PG compared to that of DCA was expected, as the presence of oxygen in the aliphatic chain has been reported to have a negative impact on the AA of the monomers or the lignins. The methoxy group contiguous to the aromatic OH plays a crucial role in the AA, as highlighted by the high IC₅₀ value of hydroxyethyl phenol HEP (3145,6±225,6 μM). This effect can be explained by the lack of functional groups to stabilize the radical. Following the same reasoning, an extra methoxy substituent should increase the AA. However, DSA showed similar AA to DCA.

In order to benchmark the lignin-derived monomers against the commercial antioxidants BHT and TBHQ, the AA of BHT and TBHQ was measured. The results obtained for BHT and TBHQ match previously reported results. Both DCA and DSA, showed higher AA than BHT, but lower than TBHQ. In these and other commercial antioxidants, t-butyl structure is often used to stabilize the radical. To compare the contribution of the tert-butyl structure against the methoxy group hydroxypropyl di-tert-butyl phenol (HPDTBP) was synthesized. Its IC₅₀ of 111 μM is close to that of the TBHQ. This result shows that methoxy groups, characteristic of lignin, are better stabilizers of radicals than t-butyl groups. This holds great potential for bio-based antioxidants.

Tronsesterificotion of lignin-derived monomers

The group of Epps has elegantly shown how lignin-derived monomers can be incorporated into polymers. Monofunctional monomers such as PG and PS were (meth)acrylated and copolymerized with other acrylates. This ensured that thermoplastic polymers were obtained. When catechol (bifunctional) type of structures were present cross-linked thermosets were obtained. Chemical (meth)acrylation of bifunctional monomers such as DCA leads to diacrylates that result in thermoplastic polymers. Our approach for selective (meth)acrylation of the aliphatic alcohols of lignin-derived monomers is to use Novozym 435, an immobilized lipase. This process, compared to chemical synthesis, fulfills several principles of green chemistry: atom-economy, safer chemicals (as it avoids the toxic acryloyl chloride) and avoids the use of an auxiliary solvent as the best performance of this enzyme is in a solvent-free medium as demonstrated for a range of monomers by Heeres et al., 2019.

Polymerization

(meth)acrylated lignin-derived monomers were co-polymerized with other monomers: methyl methacrylate (MMA), hydroxyethyl methacrylate (HEMA) and 1,4-butanediol monoacrylate (BDMA), see Table 2 below. Initially, bulk polymerization was attempted, but the uncontrolled results led us to perform the reaction in solvent. Polymers were characterized by DSC, GPC and ¹H NMR (See supplementary information). A code is given to each polymer to note the weight % of the lignin-derived monomer (1, 5 or 10), whether this is methacrylated or acrylated (M/A) and the co-monomer (MMA, HEMA or BDMA). For one of the examples, DCA extracted from lignin was used, and is marked as DCA*. In another case, 5 wt% of trimethylolpropane triacrylate (TMPTA) was added to obtain a crosslinked product.

Table 2

Antioxidant activity ( AA )

Poly HEMA (PHEMA) lacks antioxidant activity, see L. Polakova et al., 2015, wherein Fig. 6 therein illustrates for PHEMA an antioxidant activity quasi identical to the blank. However, the incorporation of as little as 1% of DCA into its backbone resulted in AA, see Table 3. Table 3 illustrates the IC₅₀ of the copolymers of HEMA previously presented in Table 2, and the standard deviation of the measurements.

Table 3

The inventors have found out that the incorporation of as little as 1% of a monomer as described by formula V provides for the surprising effect of imparting antioxidant activity to the obtained copolymers. The obtained PHEMA based hydrogels having an antioxidant feature are highly desirable in numerous applications in the biomedical field, such as wound healing.

This activity linearly increased with the increasing amount of monomer, see Fig. 2. The theoretical correction of the AA of these polymers to simulate 100 w% of m- DCA instead of 1, 5 and 10% their activity shows 6,2±0,4; 7,2±0,9 and 6,4±0,7 μg/mL respectively. These values are very close to the IC₅₀ of methacrylated DCA (6,8±0,2 μg/mL). These experiments prove that the AA of the (meth)acrylated monomers remains after the polymerization and that it is linearly dependent on the concentration of the lignin-derived monomer.

Although expected, it was reassuring to see that the DCA extracted from lignin behaved as its synthetic analog, see Fig. 2 and/or Fig. 3, wherein Fig. 3 illustrates the AA of HEMA m-DCA copolymers, wherein the m-DCA was either synthetic or lignin-extracted. More of a surprise was to see that when acrylated DCA was incorporated the AA increased, even after correction for the lower share of DCA in m-DCA compared to a-DCA on an equal weight basis. A hypothesis that needs further experiments is that the lack of methyl group results in a more ordered polymer structure, possibly improving the antioxidant properties. The copolymer containing methacrylated DSAalso showed higher AA than that containing M-DCA. This is a 27% difference, precisely the same found for individual monomers.

In order to see the effect of the co-monomer, M-DCA was co-polymerized with HBMA. It showed an IC₅₀144,0±27,4 μg/mL, higher than when the monomer was HEMA. The main reason is attributed to the lower solubility in methanol, but the steric hindrance from the longer alkyl chain could also contribute.

Although the biomedical application is of high interest, having antioxidant activity in a coating would be equally attractive. To that end, the thermoset prepared adding 5% of TMPTA was tested for antioxidant activity. In this case, the polymer was ground to a powder and a solution was made as a suspension before measuring it. The IC₅₀ value was 78,8±2,8 μg/mL, 19% lower than the corresponding thermoplastic, which can be explained by its lower solubility. Solubility was also a major issue when performing the test for the poly MMA with incorporated DCA. DPPH tests are usually performed in methanol. Measurements in 1,4-dioxane were performed but degradation of the DPPH solution was observed. Consequently, we turned back to methanol, and the same surface reaction method previously used for the thermoset was applied. It resulted in an ICsoof 189,6±15,5 μg/mL. Altogether, these experiments show that solubility is key in the antioxidant activity of the polymers. The AA of the synthesized polymers can be seen in Fig. 4.

References:

Heeres, A.; Vanbroekhoven, K.; Van Hecke, W. Solvent-Free Lipase-Catalyzed Production of (Meth)Acrylate Monomers: Experimental Results and Kinetic Modeling. Biochemical Engineering Journal 2019, 142, 162-169. https://doi.org/10.1016/j.bej.2018.11.011.

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Claims

1. A copolymer comprising at least one monomer obtained from mono(meth)acrylated monolignols and represented by formula V

wherein;

- A_k represents a C_1-6 carbon chain, including a C_1-6alkyl or C_1-6alkenyl;

2. The copolymer according to claim 1, further comprising at least one monomer represented by formula VI

wherein;

- R₄ represent a C_1-6 carbon chain optionally substituted with aryl;

- R₅ represents Hydrogen or C_1-6alkyl; and

- Ak represents a C_1-6 carbon chain, including a C_1-6alkyl or Ci- 6alkenyl;

- m is an integer ≥ 10.

3. The copolymer according to any one of claims 1 or 2, further comprising at least one (meth)acrylic monomer, preferably selected from the group consisting of methyl methacrylates, methyl acrylates, ethyl acrylates, 2- ethylhexyl acrylate, hydroxyethyl methacrylate, butyl acrylate, butyl methacrylate, 3-phenyl-propylmethacrylate.

4. The copolymer according to any one of claims 2 or 3, represented by formula VII

wherein;

- R₄ and R₃ each independently represents Hydrogen or C_1-6alkyl;

- R₅ and R₆ each independently represent Hydrogen or C_1-6alkyl; or R₅ and R6 together with the carbon atom to which they are attached form a C_3-6cycloalkyl;

- R₇ represents and a C_1-6 carbon chain, optionally substituted with aryl; and

- n and m are each independently an integer ≥ 1.

5. A method for the manufacture of the copolymers according to any one of claims 1 to 4.

6. A method for the manufacture of the copolymers according to any one of claims 1 to 4, comprising the step of; - contacting at least equimolar amounts of a monolignols according to formula (I) with an (meth)acrylate according to formula (II) in the presence of a lipase;

(I) (II) (III) (IV)

7. The method according to claim 6, wherein the lipase is immobilized, such as on acrylic beads.

8. The method according to any one of claims 6 to 7, wherein the step of contacting at least equimolar amounts of a monolignols according to formula (I) with an (meth)acrylate according to formula (II), is performed in the presence of a lipase and a polymerization inhibitor.

9. The method according to claim 8, wherein the polymerization inhibitor is selected from 4-tert-Butylpyrocatechol; tert-Butylhydroquinone; 1,4- benzoquinone; 6-tert-Butyl-2,4-xylenol; 2-tert-Butyl-l,4-benzoquinone; 2,6- Di-tert-butyl-p-cresol; 2,6-di-tert-butylphenol; 1,1-diphenyl-2-picrylhydrazyl Free Radical; hydroquinone; 4-methoxyphenol; pPhenothiazine; more in particular 4-methoxyphenol (500 ppm) and phenothiazine (500 ppm).

10. The method according to any one of claims 6 to 9; comprising the step of purifying the obtained mono-(meth)acrylated monolignols of formula (III) from the reaction mixture by filtering/decanting insolubles and distilling off the excess of (meth)acrylate (II).

11. The method according to any one of claims 6 to 10, comprising the step of a radical polymerization reaction of the mono(meth)acrylated monolignols of formula (III) using a radical initiator in an appropriate solvent.

12. The method according to claim 11, wherein the radical initiator is an azo compound; in particular azo compounds selected from azobisisobutyronitrile (AIBN) or 1,1'-azobis(cyclohexanecarbonitrile) (ABCN).

13. The method according to claim 11, wherein the solvent is chosen from dioxane, THF, methanol, ethanol, DMF.

14. The method according to any one of claims 11 to 13, wherein the radical polymerization reaction is performed on a mixture of the mono(meth)acrylated monolignols of formula (III) with a second monomer, preferably a (meth)acrylic monomer.

15. The method according to claim 14, wherein said second monomer is selected from methyl methacrylates, , methyl acrylates, ethyl acrylates, ethyl methacrylate, 2-ethylhexyl acrylate, acrylates from other Guerbet alcohols, methacrylates from Guerbet alcohols, , butyl acrylate, butyl methacrylate, propyl acrylate, propyl methacrylate, 3-phenyl-propylmethacrylate, citronellyl acrylate, geranyl acrylate, neryl acrylate, prenyl acrylate, citronellyl methacrylate, geranyl methacrylate, neryl methacrylate, prenyl methacrylate, other acrylates and methacrylates of terpene alcohols.