Chemical functionalization of cellulosic materials with diazo compounds

Abstract

The present invention relates to a method for chemically functionalizing a cellulosic material using a diazo compound, to a cellulosic material functionalized using the method, and to the use of the functionalized cellulosic material obtained thereby in various applications.

Description

[0001] Related Applications

[0002] This application claims priority from European Patent Application No. EP20175498.3 filed on May 19, 2020, the entire contents of which are incorporated herein by reference. Background of the Invention

[0004] Cellulose is a polysaccharide composed of a supramolecular arrangement of linear chains of D-glucose units linked by a dense network of β(1-4)-linked hydrogen bonds (Hon et al., Cellulose, 1994, 1: 1-25; Isogai, Material science of cellulose. Tokyo University Press: Tokyo: 2001, Belgacem & Gandini, Monomers, polymers and composites from renewable resources. Elsevier: 2011). Due to its biocompatibility, low cost, thermal and chemical stability, and worldwide availability, cellulose is the ultimate sustainable biomaterial, with an estimated annual biomass production of more than 10 tons in the plant kingdom (Klemm et al., Angew. Chem. Int. Ed., 2005, 44: 3358-3393). Although textiles and paper are its most important uses in terms of volume, cellulose is also used to make high-value materials (Kim et al., Int. J. Precis. Eng. Manuf. Green TechnoL, 2015, 2:197-213), in catalysis (Koga et al., J. Mater. Chem., 2011, 21:9356-9361; Koga et al., Molecules, 2015, 20:1495-1508; Rull-Barrull et al., Angew. Chem. Int. Ed., 2016, 55:13549-13552), in sensing (Rull-Barrull et al., Chem. Commun., 2016, 52:2525-2528; Rull-Barrull et al., Chem. Commun., 2016, 53:2535-2538), and in the manufacture of biomaterials (Kim et al., Int. J. Precis. Eng. Manuf. Green TechnoL, 2015, 2:197-213). al., Chem. Commun., 2016, 52: 6569-6572; Wang et al., Biosens. Bioelectron., 2013, 50: 262-268; Xiao et al., RSC Adv., 2013, 3: 5318-5323; Gomes et al. al., Biosens. Bioelectron, 2015, 65: 54-61), remediation (Gurgel et al., Bioresour. TechnoL, 2008, 99: 3077-3083; d'Halliun et al., ACS Sustainable Chem. Eng., 2017, 5: 1965-1973; Nongbe et al., Cellulose, 2018, 25: 4043-4055; Aka et al., J. Environ. Sci., 2019, 84: 174-183), self-cleaning materials (Geissler et al., Cellulose, 2014, 21: 357-366; Bongiovanni et al., Colloids and Surfaces A:Physiochem.Eng.Aspects,2013,418:52-59;Bretel et al.,ACS Omega,2018,3:9155-9159;Nongbe et al.,Cellulose,2018,25:1395-1411), drugs (Cauwel etal.,Chem.Commun.,2019,55:10158-10161;Jirakittiwut et al.,RSC Adv., 2015, 5: 24110-24114; Tischer et al., Biomacromolecules, 2013, 14: 4340-4350; Tischer et al., Adv. Mater., 2014, 26: 4087-4092; Yu et al. al., Langmuir, 2012, 28: 11265-11273; Wang et al., Chem. Commun., 2015, 51: 11630-11633) and covalent printing (Bretel et al., ACS Omega, 2018, 3: 9155-9159; Rull-Barrull et al. al.,J.Mat.Chem.C,2017,5:5154-5162; Bretel etal.,ACS Applied Polymer Materials,2019,1:1240-1250). .

[0005] Chemical functionalization of the hydroxyl groups on the glucose units of cellulose is an important requirement for preparing raw materials with physical properties different from those of raw cellulose (Luo et al., Sci. China Chem., 2014, 57: 1672-1682; Roy et al., Chem. Soc. Rev., 2009, 38: 2046-2064; Malmstrom et al., Polym. Chem., 2012, 3: 1702-1713). Functionalization of raw cellulose by chemical synthesis is not trivial because the dense hydrogen bond network strongly affects the reactivity of the hydroxyl groups and the solubility in water and most organic solvents. Cellulose pulp and cellulose powder can be dissolved in a tailored medium that associates a polymer solvent (dimethylformamide (DMF), dimethylacetamide (DMA) or dimethyl sulfoxide (DMSO)) with a dissolved salt (lithium chloride (LiCl) or tetra-n-butylammonium fluoride (TBAF)) (Liebert et al., Biomacromolecules, 2005, 6:333-340). Alternatively, the use of ionic liquids has also been described to effectively dissolve cellulose (Hufendiek et al., Biomacromolecules, 2014, 15:2563-2572; Schenzel et al., Green Chem., 2014, 16:3266-3271). The use of these specific solvents allows partial disruption of the hydrogen bond network to increase the reactivity of the hydroxyl groups and thus facilitate chemical functionalization. Functionalizing cellulose paper and fabrics is even more difficult because the inherent inertness of cellulose is amplified by the bulk nature of these materials due to mass transfer limitations, and the use of a dissolution medium is prohibited, otherwise the physical integrity of the material will be destroyed. Direct chemical functionalization of a large number of celluloses (paper and fabrics) mainly relies on the esterification of C6-alcohols (Geissler et al., Cellulose, 2014, 21: 357-366; Hansson et al., ACS Appl. Mater. Interfaces, 2009, 1: 2651-2659; Carlsson et al., Polym. Chem., 2012, 3: 727-733; Lee et al., Bull. Korean Chem. Soc., 2014, 35: 1545-1548) and silanization (Yang et al., Colloid Interface Sci., 2008, 325: 588-593; Wang et al., PloS One, 2016, 11) methods.Although the simplicity of implementation and the satisfactory degree of substitution (> 10%) generally obtained are the main advantages of these methods, their time efficiency is poor, and the corresponding ester or siloxane bonds are subjected to moderate stability under hydrolysis conditions. The latter disadvantage can be solved by tosylation of C6-alcohols, followed by replacement of tosylate groups with amine or azide anions. This method allows the generation of stable CN bonds, but requires at least two chemical steps (Nongbe et al., Cellulose, 2018, 25: 1395-1411).

[0006] Therefore, there remains a need in the art for chemical functionalization strategies for bulk cellulose that are compatible with industrial environments. Summary of the invention

[0007] The inventors have identified a new method for the efficient functionalization of cellulose in paper or fabric form using diazo compounds. Compared to known conventional methods, the proposed functionalization reaction occurs in a single step and allows rapid grafting via covalent ether bonds resistant to hydrolytic conditions. The reaction is therefore compatible with industrial production rates and is also respectful of the environment, since nitrogen (N2) is the only by-product released. In terms of grafting levels, the reaction can be carried out efficiently in the presence of a rhodium catalyst or photochemical activation, compared to the absence of any catalysis or photoactivation.

[0008] Thus, the present invention provides a method for functionalizing a cellulosic material, comprising the steps of contacting the cellulosic material with a diazo compound to obtain a functionalized cellulosic material. The cellulosic material is typically a mercerized cellulosic material.

[0009] In certain embodiments, functionalization occurs via the formation of an ether bond.

[0010] In certain embodiments, the cellulosic material used in the functionalization method is in the form of fabric, paper, or paperboard.

[0011] In certain embodiments, the cellulosic material comprises raw cellulose. In certain embodiments, the cellulosic material consists of raw cellulose.

[0012] In certain embodiments, the diazo compound used in the functionalization method is stabilized by at least one electron withdrawing group.

[0013] In certain specific embodiments, the diazo compound stabilized with at least one electron withdrawing group has one of the following formulae:

[0014]

[0015] In certain embodiments, the functionalization is performed in a solvent selected from the group consisting of a non-polar solvent, a polar aprotic solvent, and any combination thereof.

[0016] In certain embodiments, the functionalization is carried out at a temperature comprised between room temperature and reflux temperature.

[0017] In certain embodiments, functionalization occurs in the presence of a rhodium (II) carboxylate used as a catalyst or in the presence of photochemical activation (eg, photochemical activation with UV light).

[0018] In other embodiments, the functionalization is performed in the absence of a catalyst and in the absence of any photochemical activation.

[0019] The present invention also relates to the use of the method as described herein for functionalizing a cellulosic material with a functional group selected from the group consisting of a hydrophobic agent, a catalyst, a sensing agent, a diagnostic agent, a printing agent, a chelating agent, a ligand, an antioxidant, an antimicrobial agent and a drug.

[0020] In certain embodiments, the hydrophobic agent belongs to the family of saturated fatty acids and related compounds, the diterpenoid family, or the sterol family.

[0021] In certain embodiments, the hydrophobic agent is selected from the group consisting of cholesterol, palmitic acid, and abietic acid.

[0022] The invention further relates to the use of a method as described herein for the manufacture of one of the following: a hydrophobic cellulosic material, a packaging material, a cellulose-supported catalyst or a security element.

[0023] The present invention also relates to a functionalized cellulosic material obtained using the process as described herein.

[0024] The present invention also relates to the use of the functionalized cellulose material in the manufacture of packaging, catalysis, filtration, adsorption and water treatment, remediation, medicine, anti-counterfeiting, paper-based electronic devices or clothing, protective clothing, health care materials, medical devices, trust products, official documents or labels.

[0025] These and other objects, advantages and features of the present invention will become apparent to those of ordinary skill in the art from a reading of the following detailed description of the preferred embodiments.

[0026] BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 .Grafting reaction of 4 different diazo compounds onto cellulose.

[0028] Figure 2 The grafted cellulose Cell-4 complexes with palladium, resulting in the formation of the complex Cell-5.

[0029] Figure 3 .Chemical structures and names of nine starting substrates used to synthesize diazo hydrophobic inks.

[0030] Figure 4 Images of cellulose materials after grafting with (A) cholesterol (using NaOH 2M (left) or NaOH 4M (right)), or with (B) palmitic acid (using NaOH 2M (left) or NaOH 4M (right)), or with (C) rosin acid (using NaOH 2M (left) or NaOH 4M (right)).

[0031] definition

[0032] Throughout this specification, several terms are used which are defined in the following paragraphs.

[0033] The term "acyl" as used herein refers to a -C(=O)R (or -COR) group, wherein R is selected from alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl or heterocyclyl, and wherein the alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl or heterocyclyl may be optionally substituted.

[0034] The term "aldehyde" as used herein refers to a -C(=O)H group.

[0035] The terms "amide" and "amido" are used interchangeably herein and refer to -C(=O)NRR', wherein R and R' are each independently selected from hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl or heterocyclyl, and wherein the alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl or heterocyclyl may be optionally substituted.

[0036] The term "ester" as used herein refers to a -C(=O)-OR group, wherein R is selected from hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl or heterocyclyl, and wherein the alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl or heterocyclyl may be substituted or unsubstituted.

[0037] As used herein, the term "nitrile" refers to a -C≡N group.

[0038] The term "nitro" as used herein refers to a -NO2 group.

[0039] The term "sulfonyl" as used herein refers to a -S(=O)2-R radical, wherein R is selected from hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl or heterocyclyl, and wherein the alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl or heterocyclyl may be optionally substituted.

[0040] The term "aryl" as used herein refers to an aromatic ring or ring system consisting of one or more rings, preferably one to three rings (fused or unfused), wherein the ring atoms are completely composed of carbon atoms. Examples of aryl include phenyl, biphenyl, naphthyl, phenanthrenyl, anthracenyl, indolyl, etc. Aryl can be substituted or unsubstituted.

[0041] The term "alkyl" as used herein describes a saturated aliphatic hydrocarbon including straight and branched groups. Preferably, the alkyl group has 1 to 20 carbon atoms. Whenever a numerical range (e.g., "1-20") is stated herein, it means that the group (in this case, an alkyl group) may contain 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., up to and including 20 carbon atoms. In certain embodiments, an alkyl group is a medium-sized alkyl group with 1 to 10 carbon atoms. Examples of alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, amyl, isopentyl, hexyl, heptyl, octyl, nonyl, decyl, etc. Alkyl groups may be substituted or unsubstituted.

[0042] The term "cycloalkyl" as used herein describes an all-carbon monocyclic or fused ring (i.e., rings that share adjacent pairs of carbon atoms) group in which one ring (or multiple rings) does not have a completely conjugated π electron system. Saturated monocyclic cycloalkyl rings include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cyclooctyl. Saturated bicyclic and polycyclic cycloalkyl rings include, for example, norbornane, bicyclo[2.2.2]octane, decalin, and adamantane. Cycloalkyl can be substituted or unsubstituted.

[0043] The term "alkenyl" as used herein refers to a straight or branched hydrocarbon group of 2 to 20 carbon atoms containing at least one carbon-carbon double bond (-C=C-). Examples of alkenyl groups include ethenyl, n-propenyl, isopropenyl, n-butenyl, isobutenyl, isobutenyl, octenyl, decenyl, tetradecenyl, hexadecenyl, eicosene, tetracosene, etc. Alkenyl groups may be substituted or unsubstituted.

[0044] The term "cycloalkenyl" as used herein refers to an unsaturated cyclic hydrocarbon group having at least one carbon-carbon double bond. A cycloalkenyl group can be a monocyclic (C3-C 10 ) or polycyclic (e.g., fused, spiro or bridged bicyclic (C5-C 12 )). Examples of cycloalkenyl groups include, but are not limited to, cyclopropenyl, cyclobutenyl, cyclohexenyl, 1,3 or 1,4 cyclooctadienyl, cycloheptenyl, cycloheptadienyl, cyclooctenyl, bicyclooctenyl, etc. The cycloalkenyl group may be substituted or unsubstituted.

[0045] The term "alkynyl" as used herein refers to a straight or branched C1-C12-yl group having at least two carbon atoms connected by a triple bond (-C≡C-). 20Examples of alkynyl groups include, but are not limited to, ethynyl, propynyl, 1-butynyl, 2-butynyl, isobutynyl, sec-butynyl, butadiynyl, 1-pentynyl, 2-pentynyl, isopentenyl, 1,3-pentadiynyl, 1,4-pentadiynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 1,3-hexadiynyl, 1,4-hexadiynyl, 1,5-hexadiynyl, 2,4-hexadiynyl, or 1,3,5-hexadiynyl. Alkynyl groups may be substituted or unsubstituted.

[0046] The term "cycloalkyl" as used herein refers to a non-aromatic carbonyl ring consisting of at least seven carbon atoms and containing at least one carbon-carbon triple bond. Examples of cycloalkynyl include, but are not limited to, cycloheptynyl, cyclooctynyl, cyclononynyl, etc. Cycloalkynyl can be substituted or unsubstituted.

[0047] As used herein, the term "heterocycle" refers to a cyclic group containing at least one sulfur, nitrogen or oxygen ring atom. The heterocyclyl group can be a heterocycloalkyl, heterocycloalkenyl, heterocycloalkynyl or heteroaryl. Examples of heterocyclic groups include, but are not limited to, furanyl, thienyl, pyrazolyl, pyrrolyl, methylpyrrolyl, imidazolyl, indolyl, thiazolyl, oxazolyl, isothiazolyl, isoxazolyl, piperidinyl, pyrrolinyl, piperazinyl, quinolinyl, triazolyl, tetrazolyl, isoquinolinyl, benzofuranyl, benzothienyl, morpholinyl, benzoxazolyl, tetrahydrofuranyl, pyranyl, indazolyl, purinyl, indolinyl, pyrazolinyl, imidazolinyl, imidazoindolyl, pyrrolidinyl, furazanyl, N-methylindolyl, methylfuranyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyridinyl, epoxy, aziridinyl, oxetanyl, azetidinyl, pyridinyl, N-oxides of pyrazinyl and pyrimidinyl, and the like.

[0048] When used to characterize a chemical group in this article, the term "substituted" means that the chemical group may have one or more hydrogen atoms replaced by non-hydrogen substituents. In the context of the present invention, a chemical group (e.g., aryl, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl or heterocyclic) is substituted to the extent that the substitution is chemically meaningful. Examples of substituents include, but are not limited to, nitro (-NO2), sulfonyl, cyano, halogen (F, Br, Cl, I), alkyl, amino (-NR'R", wherein R' and R" are each independently H, alkyl, cycloalkyl or heteroaryl), hydroxyl (-OH), alkoxy (-OR', wherein R' is alkyl), aryloxy (-OAr, wherein Ar is aryl), aldehyde (-C(=O)H), acyl, ester, alkylthio (-SR', wherein R' is alkyl), arylthiol (-SAr, wherein Ar is aryl), carboxyl (-COOH or -COOM, wherein M is a suitable cation, such as sodium or potassium), amide (-C(=O)NR'R" or -NR'-C(=O)R", wherein each of R' and R" is independently H, alkyl, cycloalkyl or heteroaryl), oxo (O=), alkylsilyl (-SiR'R"R"', wherein each of R', R", R"' is alkyl), and the like.

[0049] As used in this document, the terms "about" and "approximately" with respect to numbers generally include numbers that fall within 10% range (greater or less than the number) in either direction of the number, unless otherwise specified or warranted from the context (unless such a number would exceed 100% of the possible value).

[0050] DETAILED DESCRIPTION OF CERTAIN PREFERRED EMBODIMENTS

[0051] As mentioned above, the present invention relates to a method for functionalizing a cellulosic material using a diazo compound, to a functionalized cellulosic material synthesized using the method, and to the use of the functionalized cellulosic material obtained thereby in various applications.

[0052] I-Functionalization of Cellulosic Materials

[0053] The method for functionalized cellulose material according to the present invention comprises contacting cellulose material with diazo compound to produce the step of functionalized cellulose material. As used herein, term "functionalization" relates to the modification of solid substrate to provide multiple functional groups on substrate surface. As used herein, "functionalized" surface refers to the substrate surface that has been modified so that multiple functional groups are present thereon. Preferably, functionalization refers to adding functional groups on the surface of solid substrate in order to modify or improve its performance. Some of these properties can be hydrophobicity, antioxidant and / or antibacterial ability, high mechanical strength, etc. (see below).

[0054] 1. Cellulose materials

[0055] The material to be functionalized according to the method of the present invention is a cellulosic material. As used herein, the term "cellulosic material" refers to a solid support containing cellulose, optionally mixed with other substances.

[0056] Cellulose has the formula (C6H 10 O5) n A polysaccharide consisting of a linear chain of several hundred to several thousand β(1→4) linked D-glucose units. In this formula, the number n of D-glucose units depends substantially on the type of cellulose and / or cellulosic material used and is typically 15-15,000. The cellulose constituting the cellulosic material used in the functionalization method described herein can be derived from any suitable source known in the art, including from wood (e.g., wood from softwood trees such as spruce, fir, larch or pine, or wood from hardwood trees such as birch, poplar, poplar, ebony, alder, eucalyptus or acacia, or from a mixture of softwood and hardwood), from agricultural residues, grasses or other plant matter (e.g., straw, leaves, bark, seeds, shells, flowers, vegetables or fruits from cotton, flax, corn, wheat, oats, rye, barley, rice, flax, hemp, jute, ramie, kenaf, bagasse, bamboo or reed), or from algae, fungi or bacteria.

[0057] The cellulose material used in the functionalization method described herein is a solid carrier. The terms "solid carrier", "solid matrix", "carrier" and "matrix" are used interchangeably in this article. They refer to materials with one or more rigid, semi-rigid or flexible surfaces. The solid carrier can be porous or non-porous. The solid carrier can optionally be able to absorb liquid (e.g., due to porosity), but is typically rigid enough so that it does not swell substantially when absorbing liquid, and does not shrink substantially when removing liquid by drying. Non-porous solid carriers are generally impermeable to liquids or gases.

[0058] In particular, the functionalization process according to the invention can be applied to cellulosic materials in the form of textiles, paper or paperboard.

[0059] As used herein, the term "fabric" refers to any woven, nonwoven, knitted, felted, tufted, knotted, crocheted or otherwise formed sheet structure, which is produced by any natural or artificial fiber, yarn or its substitute or used in combination with it. Fabric can be a textile, cloth, fabric material, fabric garment or other fabric product. The terms "fiber" and "textile fiber" are used interchangeably herein, and refer to a material unit that can be spun into yarn or made into fabric by bonding or by interweaving in various ways, including, for example, weaving, knitting, braiding, felting, twisting, webbing, knotting or crocheting. Fiber is a fine material with a high length to thickness ratio. As used herein, the term "yarn" refers to the continuous strand of textile fiber, which can be made of endless filaments or shorter fibers that are twisted or otherwise kept together, and its form is suitable for weaving, knitting, braiding, felting, twisting, webbing or otherwise making fabric. In the context of the present invention, the fabric may comprise, in addition to cellulose (e.g., hemp, flax, cotton, ramie, jute and sisal), natural or synthetic fibers selected from the group consisting of wool, silk, thermoplastic aliphatic polymers, polyesters, polyamides, polyimides, polypropylene, polyethylene, polystyrene, polytetrafluoroethylene, fiberglass, polytrimethylene esters, polycarbonates, polyester terephthalates, polybutylene terephthalate, and any combination thereof.

[0060] As used herein, the term "paper" refers to a sheet or roll produced from cellulose fibers, optionally in combination with other fibrous materials such as ceramic fibers, glass fibers, slag fibers, carbon fibers, polyamide fibers, viscose fibers and mineral fibers. The resulting sheet has dimensions in two dimensions of width and length that are many orders of magnitude larger than the third dimension of thickness. Paper typically has a thickness of 0.1-0.3 mm. The basis weight (or grammage) of paper can be 20-120 g / m 2 .

[0061] The term "paperboard" is a general term for heavy-duty paper-based products that have greater thickness and excellent durability or other specific paper mechanical properties, such as foldability, rigidity, and impact resistance. "Paperboard" includes pasteboard, paperboard, and corrugated fiberboard. The terms "pasteboard," "cardstock," and "cover stock" are used interchangeably herein and refer to paper that is thicker and more durable than ordinary writing or printing paper, but thinner and more flexible than other forms of paperboard. Pasteboard is commonly used for business cards, postcards, playing cards, catalog covers, scrapbooks, and other uses that require greater durability than ordinary paper. Typical basis weights for pasteboard are 135-300 g / m 2As used herein, the term "cardboard" refers to a thick paper base material with a thickness exceeding 0.30 mm, which exhibits higher foldability and rigidity than paper. Cardboard is generally defined as a paper material with sufficient thickness to maintain shape when formed into a tube, and is generally used for folding cartons, assembly boxes, card packaging, etc. It usually has a thickness of 250 g / m 2 The terms "corrugated fiberboard" and "corrugated paperboard" are used interchangeably herein and refer to a combination of paperboard that is typically composed of two flat liners and an inner grooved corrugated medium. It is often used to make boxes for shipping or storing products.

[0062] In certain embodiments, the cellulose in the cellulosic material to be functionalized according to the methods described herein is virgin cellulose. As used herein, the term "virgin cellulose" refers to cellulose that has not undergone any treatment that results in a change in its chemical formula.

[0063] In other embodiments, the cellulose in the cellulosic material may be partially chemically derivatized, for example, by carboxylation, oxidation, esterification, or any other suitable reaction, as long as the chemical modification does not introduce groups that react with the diazo compound or prevent the hydroxyl groups of the cellulose from reacting with the diazo compound. The term "partially chemically derivatized" when used herein to characterize cellulose refers to cellulose containing D-glucose units having at least one hydroxyl group that has not been affected by derivatization, including, for example, cellulose acetate (which is one of the earliest synthetic fibers), cellulose sulfate, carboxymethyl cellulose, or methyl cellulose.

[0064] Prior to functionalization, the cellulosic material is subjected to a mercerization step. As used herein, the term "mercerization" has its meaning as understood in the art and refers to a method of treating a cellulosic material with an alkali. In the mercerized cellulose, intramolecular and intermolecular hydrogen bonds are broken, so mercerization changes the macrostructure of the cellulose. The mercerization step can be performed using any mercerization method known in the art, including standard mercerization, which is performed in a 10 mass % NaOH solution at room temperature for 24 hours, or rapid mercerization, which is performed by depositing a 10 mass % NaOH solution on the cellulosic material for 15 minutes at room temperature. The mercerization step is usually followed by washing the obtained mercerized cellulosic material (e.g., with ethanol) until a neutral pH is obtained.

[0065] 2. Diazo compounds

[0066] The reagents in the functionalization reactions described herein are diazo compounds.

[0067] The terms "diazo" and "diazo compound" are used interchangeably herein. They refer to a class of highly reactive compounds having the following general formula: R 1 R 2C=N2. In the context of the present invention, diazo compounds suitable for the functionalization methods described herein are diazo compounds that readily insert into CH and XH bonds (wherein X is Si, N, S or O) as carbene equivalents. Such suitable diazo compounds include diazo compounds stabilized by electron withdrawing substituents. The term "electron withdrawing" as used herein to characterize a group or substituent has its meaning as understood in the art and refers to the tendency of the group or substituent to attract valence electrons from adjacent atoms, i.e., the substituent is electronegative relative to the adjacent atoms.

[0068] Diazo compounds stabilized by electron-withdrawing substituents include the general formula R 1 R 2 C=N2 diazo compound, where R 1 and R 2 is a substituent independently selected from acyl, aldehyde, amide, ester, nitrile, nitro, sulfonyl and aryl as defined above, or wherein R 1 and R 2 connect to form an aromatic group, or wherein R 1 is selected from acyl, aldehyde, amide, ester, nitrile, nitro, sulfonyl and aryl, and R 2 is hydrogen or an alkyl group (particularly a straight chain, branched chain, cyclic or polycyclic alkyl group containing 12 or fewer carbon atoms).

[0069] The diazo compounds used in the functionalization methods according to the present invention can be obtained from commercial sources or can be prepared using procedures known in the art.

[0070] For example, the diazo compound can be composed of an α-receptor substituted aliphatic primary amine (R a -CH2-NH2, where R aThe invention relates to a kind of diazo compound, wherein the diazo compound is prepared by reacting nitrous acid with nitrous acid (COOR, CN, CHO or COR), and the diazo compound is produced by reacting nitrous acid. Alternatively, the diazo compound can be formed by the electrophilic substitution reaction between acyl halide and diazomethane. Ketone (including 1,3-diketone), ester (including β-keto acid ester), acyl chloride and carboxylic acid can be converted into diazo compound (Davies, J.Am.Chem.Soc.1993,115,9468-9479) by using diazo transfer conditions and suitable transfer reagents (such as aromatic and aliphatic sulfonyl azide, such as toluenesulfonyl azide, 4-carboxylbenzenesulfonyl azide, 2-naphthalenesulfonyl azide, methylsulfonyl azide, etc.) and suitable bases (for example, triethylamine, triisopropylamine, diazobicyclo [2.2.2] octane, 1,8-diazabicyclo-[5.4.0] undecyl-7-ene, etc.). Alternatively, the diazo compound can be formed from aliphatic amines, anilines or other aryl amines or hydrazines using a nitrosating agent (e.g., sodium nitrite) and an acid (e.g., p-toluenesulfonic acid) (Zollinger, Diazo Chemistry I and II, VDH Weinheim, 1994). Diazo compounds can also be obtained by elimination reactions of N-alkyl-N-nitroso compounds ("Organic Syntheses", 1988, Vol. 6, 981), or from azides and hydrazine precursors (Myers and Raines, Angew. Chem. Int. Ed., 2009, 48: 2359-2363). Alternatively, alkyl nitrile reagents (e.g., (3-methylbutyl) nitrile) can be used to convert α-amino esters into corresponding diazo compounds in non-aqueous media (Takamura, Tetrahedron, 1975, 31: 227). Those skilled in the art will recognize that the method for preparing the diazo compound is not a limiting factor. Following preparation, if desired or necessary, the diazo compound can be purified prior to use in the functionalization methods described herein. Methods for purification of diazo compounds are known in the art.

[0071] 3. Functionalization reaction

[0072] The method for functionalizing a cellulosic material according to the present invention comprises the step of contacting a cellulosic material with a diazo compound to produce a functionalized cellulosic material. As described above, prior to functionalization, the cellulosic material is subjected to a mercerization step. In other words, in the method for functionalizing a cellulosic material according to the present invention, the cellulosic material is a mercerized cellulosic material (i.e., a cellulosic material that has been subjected to mercerization) - however, the term "mercerization" is often omitted hereinafter. Therefore, the method for functionalizing a cellulosic material according to the present invention comprises the step of mercerizing a cellulosic material to obtain a mercerized cellulosic material or to provide a mercerized cellulosic material; and the step of contacting a mercerized cellulosic material with a diazo compound to produce a functionalized cellulosic material.

[0073] The contacting step is carried out under conditions (e.g., temperature, time, solvent) that allow the diazo compound to react with the cellulosic material according to the following reaction, which is shown in the case of raw cellulose:

[0074]

[0075] Functionalization is carried out by forming an ether bond. The terms "ether linkage" and "ether bond" are used interchangeably herein and refer to a chemical bond of two substituted or unsubstituted groups through an oxygen atom, i.e., RO-R', such that neither R nor R' contains another oxygen atom directly attached to the carbon atom forming the ether bond. In other words, the ether bond is not part of an acetal, ketal, glycoside, ester, or orthoester moiety.

[0076] The functionalization method according to the present invention is a heterogeneous chemical reaction. As used herein, the term "heterogeneous chemical reaction" refers to a class of chemical reactions in which the reactants are components of two or more phases (here solid (cellulose material) and liquid (diazo compound dissolved in solvent or diazo compound itself if it is liquid under reaction conditions)).

[0077] The term "contacting" as used herein refers to bringing together at least two different substances by dissolving, mixing, suspending, blending, dipping, immersing, adsorbing or stirring so that the at least two different substances can react. In the context of the present invention, the cellulosic material and the diazo compound are contacted in a solvent. For example, as reported in the Examples section below, the cellulosic material can be immersed in a solution of the diazo compound dissolved in a solvent.

[0078] A.Solvent

[0079] In the functionalization reaction according to the present invention, the solvent is selected according to the ability of the solvent to dissolve the diazo compound. As known to those skilled in the art, the solvent can be a single solvent or a mixture of at least two different solvents. Usually, the solvent is an organic solvent, preferably selected from non-polar solvents, polar aprotic solvents and combinations thereof. Examples of non-polar solvents include, but are not limited to, pentane, cyclopentane, hexane, cyclohexane, benzene, toluene, 1,4-dioxane, chloroform, ether, methylene chloride and ethylene dichloride. Examples of polar aprotic solvents include, but are not limited to, tetrahydrofuran, ethyl acetate, acetone, dimethylformamide, acetonitrile and dimethyl sulfoxide.

[0080] Those skilled in the art know how to select a suitable solvent or solvent mixture to optimize the reaction depending on the nature of the diazo compound and the cellulosic material used as reagents.

[0081] B. Temperature

[0082] The functionalization reactions described herein can be carried out at any suitable temperature, i.e., a temperature that allows a reaction to occur between the reagents. Under the conditions used in the experiments reported in the Examples section below, the inventors have observed that, regardless of the solvent used, grafting occurs slightly better at reflux than at room temperature. Therefore, the functionalization reactions according to the present invention are preferably carried out at a temperature ranging from room temperature to reflux temperature.

[0083] In certain embodiments, the functionalization reaction is carried out at room temperature. As used herein, the term "room temperature" refers to a temperature of about 15°C to about 35°C, such as about 20°C to about 35°C. Therefore, the room temperature may be about 15°C, about 16°C, about 17°C, about 18°C, about 19°C, about 20°C, about 21°C, about 22°C, about 23°C, about 24°C, about 25°C, about 26°C, about 27°C, about 28°C, about 29°C, about 30°C, about 31°C, about 32°C, about 33°C, about 34°C or about 35°C.

[0084] In other embodiments, the functionalization reaction is carried out at reflux temperature.As used herein, the term "reflux temperature" refers to the temperature at which a solvent or solvent system refluxes or boils at atmospheric pressure.

[0085] In other embodiments, the functionalization reaction is carried out at a temperature above room temperature but below reflux temperature. For example, when the solvent is dichloromethane, the functionalization reaction can be carried out at a temperature from room temperature to 40°C; when the solvent used is dichloroethane, at room temperature to 80°C; when the solvent is toluene, at room temperature to 100°C, etc.

[0086] C. Ratio

[0087] The functionalization reaction according to the invention can be carried out using any molar ratio between the diazo compound and the cellulosic material that allows effective functionalization of the cellulosic material. A person skilled in the art knows how to choose such a molar ratio to optimize the functionalization reaction.

[0088] Under the conditions used in the experiments reported in the Examples section below, the inventors have observed that the grafting efficiency does not vary much when the number of equivalents of diazo compound per glucose unit (present in the cellulosic material) varies from 1 to 9.

[0089] Thus, in certain embodiments, the number of equivalents of the diazo compound per glucose unit (present in the cellulosic material) is from about 1 to about 30, preferably from about 1 to about 15, or from about 1 to about 10. For example, the number of equivalents of the diazo compound per glucose unit (present in the cellulosic material) may be about 1, about 1.5, about 2, about 2.5, about 3, about 3.5, about 4, about 4.5, about 5, about 5.5, about 6, about 6.5, about 7, about 7.5, about 8, about 8.5, about 9, about 9.5, or about 10.

[0090] D. Catalysis, photochemical activation

[0091] In certain embodiments, the functionalization reaction is carried out in the presence of a catalyst. The terms "catalyst" and "catalytic agent" are used interchangeably herein and refer to materials that promote the reaction. In the context of the present invention, the catalyst is a rhodium carboxylate (II). Examples of rhodium carboxylate (II) that can be used as a catalyst in the functionalization reaction include, but are not limited to, rhodium acetate (II) (Rh2(OC(=O)CH3)4 or Rh2(OAc)4), rhodium propionate (II) (Rh2(OC(=O)CH2CH3)4), rhodium butyrate (II) (Rh2(OC(=O)CH2CH2CH3)4) and the like. In certain preferred embodiments, the catalyst used is rhodium acetate (II). The rhodium carboxylate (II) catalyst is used in a concentration sufficient to catalyze the functionalization reaction. Those skilled in the art know how to determine such a concentration. For example, the concentration of rhodium carboxylate (II) can be from about 0.1mol% to about 4mol%, for example, from about 0.5mol% to about 2mol%, for example, about 1mol%. The unit "molar percent (mol %)" is the amount of catalyst (expressed in moles) divided by the total amount of glucose units (also expressed in moles) expressed in %.

[0092] In other embodiments, the functionalization reaction is carried out in the absence of a catalyst but in the presence of photochemical activation. Photochemical activation is carried out with a light source that emits ultraviolet light (UV). As used herein, the term "UV light" refers to radiation having a wavelength or peak wavelength of about 200nm to about 400nm. In the context of the present invention, photochemical activation can be carried out using any UV light emitting device known in the art, including lamps, light emitting diodes (LEDs), lasers, etc. The light source can have a specific wavelength (for example, in the examples given below, the inventors have used 254nm and 365nm), or the light source can emit a wide spectrum including UV radiation (for example, the inventors have used xenon lamps, which emit from UV to infrared (IR). Photochemical activation is generally carried out within the duration of the functionalization reaction. However, it is also envisioned that photochemical activation can be carried out for a shorter time than the entire duration of the functionalization reaction.

[0093] In other embodiments, the functionalization reaction is carried out in the absence of a catalyst and in the absence of photochemical activation. As described above, the inventors have shown that the functionalization reaction described herein can be carried out effectively in the presence of a rhodium catalyst or in the presence of photochemical activation or in the absence of any catalysis or photoactivation in terms of grafting level.

[0094] E. Reaction time

[0095] Functionalization reaction can carry out any suitable time length.Usually, reaction mixture carries out any time between a few seconds to a few hours.Depend on the property of experimental conditions, preparation scale and used cellulose material and diazo compound, reaction can carry out for example about 10 seconds, or about 30 seconds, or about 1 minute, or about 2 minutes, or about 3 minutes, or about 4 minutes, or about 5 minutes, or about 10 minutes, or about 15 minutes, or about 30 minutes, or about 45 minutes, or about 1 hour, or about 2 hours, or about 4 hours, or about 5 hours, or greater than 5 hours.

[0096] F. Post-reaction treatment

[0097] After the reaction is complete, the functionalized cellulose material can be washed with an organic solvent to remove any unreacted diazo compound and any residual rhodium-based catalyst (if a catalyst was used in the functionalization reaction). Washing can be performed in one or more stages using any method known in the art, such as by immersing the functionalized cellulose material in one or more baths, or by using a washing device (such as a rotary washing device) or an ultrasonic bath (e.g., if the synthesis is performed in an industrial setting).

[0098] After the washing step, the functionalized cellulosic material can be dried using any suitable method, for example by drying using a gas flow (e.g., air, argon, nitrogen) or by passing heated air through the cellulosic material, for example using a tumble dryer or a steam tube dryer, or by infrared irradiation, for example using an infrared dryer, or by heating, for example using a conduction dryer or a convection dryer.

[0099] G. Degree of Functionalization

[0100] Functionalized cellulosic materials obtained using the methods described herein can be analyzed to determine the degree of functionalization. The terms "functionalization degree" and "grafting level" are used interchangeably herein and refer to the proportion of hydroxyl groups (D-glucose units of cellulose) that have reacted with the diazo compound in the functionalization reaction. Thus, the degree of functionalization or degree of etherification can be determined by measuring the number of hydroxyl groups of the cellulosic material before and after the functionalization reaction. Elemental analysis can be used for such determination.

[0101] The degree of functionalization of the cellulosic material according to the methods described herein can be from about 1% to about 50%, preferably from about 1% to about 33%, in particular from about 5% to about 15%, for example about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14% or about 15%.

[0102] H. Further Modification

[0103] In certain embodiments, the functionalization methods described herein allow for the functionalization of a cellulosic material with a desired functional group, i.e., a target functional group or molecule whose presence on the surface of the cellulosic material is intended to modify or improve at least one property of the cellulosic material. In other words, in this embodiment, the diazo compound carries a desired functional group (e.g., R 1 , or R 2 , or R 1 and R 2 is the desired functional group); the final functionalized cellulose material is obtained in a single step; and the desired functional group is directly attached to the cellulose material via an ether bond. The diazo compound with the functional group can be commercially available, or a diazo derivative of the target molecule to be grafted onto the cellulose material can be first prepared (for example, the target molecule or the desired functional group can be selected from hydrophobic agents, biomolecules, drugs, analytes, catalysts, diagnostic agents, printing agents, sensing agents, etc. - see below).

[0104] In other embodiments, the functionalization methods described herein allow cellulosic materials to be functionalized with reactive moieties, which allow subsequent functionalization with desired functional groups (i.e., target molecules). As used herein, the term "reactive moiety" refers to a chemical group that can be used as a starting point for a synthetic organic method. As will be appreciated by those skilled in the art, the reactive moiety can be protected at least temporarily. In the context of the present invention, examples of suitable reactive moieties include, but are not limited to, ketones, nitriles, esters, and amides. In other words, in this embodiment, the diazo compound does not carry the desired functional group; and the final functionalized cellulosic material is obtained in a multi-step reaction. Those skilled in the art know how to select experimental conditions to covalently bind the desired functional group to the cellulosic material through the reactive moiety present on the cellulosic material. This synthesis method is particularly useful when the diazo compound of the target molecule cannot be easily prepared or when steric effects determine the physical distance between the surface of the cellulosic material and the functional group. Therefore, in certain embodiments, the diazo compound can be selected to introduce a spacer between the cellulosic material and the target functional group. For example, at least one of R1 and R2 of the diazo compound is a spacer. The terms "spacer" and "spacer group" are used interchangeably herein, and refer to a group of a covalent bond that provides a physical distance between a cellulosic material and a functional group. Preferably, the spacer group preferably does not affect the performance of the cellulosic material. Spacer groups are known in the art. Suitable spacers include, but are not limited to, alkanes, alkenes or alkynes containing up to 200 carbon atoms, for example, up to 100 carbon atoms or up to 50 carbon atoms, in a branched or straight chain, substituted or unsubstituted. In certain embodiments, the spacer group suitable for the context of the present invention contains 1-20 carbon atoms. Typically, the spacer group is stable under the conditions of using functionalized cellulosic materials. However, it is also contemplated to use a spacer group that can be decomposed under specific conditions (e.g., a spacer group that can be photodecomposed).

[0105] II – Functionalization reactions and uses of functionalized cellulosic materials

[0106] The functionalization method according to the present invention can be used to functionalize a cellulosic material with any of a variety of desired functional groups to modify or improve at least one property of the cellulosic material. The properties that can be modified or improved include, for example, physical properties such as hydrophobicity, tensile strength, tensile stiffness, color, fluorescence, etc., and chemical properties such as adsorption, chelation, antimicrobial activity, catalysis of chemical reactions, biodegradability in the presence of enzymes, etc.

[0107] 1. Hydrophobic cellulose carrier

[0108] Cellulose-based materials have a strong tendency to absorb moisture due to the high hydrophilicity of cellulose fibers. Even though this property may be interesting for certain specific uses, it can represent a major disadvantage when the mechanical resistance and physical integrity of the material are degraded by humidity. This problem is particularly prevalent for paper used for packaging or as a printing medium. The hydrophobization of cellulose allows the advantages of natural fibers to be combined with the properties of moisture resistance and water repellency.

[0109] The functionalization method according to the present invention can be used to increase the hydrophobicity of the cellulosic material. In fact, the diazo compound can be used to functionalize the cellulosic material with a hydrophobic agent. As used herein, the term "hydrophobic agent" refers to an agent that imparts hydrophobicity to the cellulose surface to which it is grafted, so that the cellulose surface is not easily wetted by polar solvents (such as water), and the cellulose surface exhibits a contact angle higher than 90° when in contact with a polar solvent, the angle being measured by a static contact angle goniometer using a static sessile drop method. For example, in certain embodiments, the cellulose surface grafted with a hydrophobic agent exhibits a contact angle higher than about 100°, or higher than about 110°, or higher than about 120°, or still higher than about 130°.

[0110] Examples of suitable hydrophobic agents include, but are not limited to, long straight or branched carbon chains containing more than 8 carbon atoms, steroid derivatives (e.g., cholesterol), terpene derivatives (e.g., limonene, myrcene, pinene, ocimene, etc.), siloxane derivatives (e.g., aliphatic or cyclic polysiloxanes, polydimethylsiloxanes or polydimethyldiphenylsiloxanes, or silane-based compounds such as alkoxysilanes and aminosilanes), fluorinated derivatives (e.g., fluorinated monomers, fluorinated oligomers, fluorinated polymers, fluorinated silanes), carbon nanotubes, manganese oxide polystyrene (MnO2 (PS) nanocomposites, zinc oxide polystyrene (ZnO / PS) nanocomposites, octadecylamine (ODA), and the like.

[0111] In certain embodiments, the hydrophobic agent belongs to the family of saturated fatty acids and related compounds, the diterpene family, or the sterol family. For example, the hydrophobic agent is cholesterol, palmitic acid, or abietic acid.

[0112] The hydrophobic cellulose material obtained by this functionalization reaction can be used for a variety of applications. For example, when the cellulose material is paper or paperboard, the hydrophobic cellulose material can be used as a packaging material. As used herein, the term "packaging material" refers to a material used to form a package for protecting, carrying, distributing, etc. products, such as a ream of paper, a paper roll, food, beverages, etc. The packaging material can include, for example, ream packaging, roll packaging, envelopes, containers (e.g., for food or beverages), boxes, etc. When the cellulose material is a fabric, the hydrophobic cellulose material can be used in the manufacture of, for example, clothing or health-related materials, such as surgical sheets, sterile packaging, diapers, incontinence products, wipes, bedding, pads, etc.

[0113] In certain embodiments, once functionalized, the hydrophobic agent causes the cellulosic material to have a contact angle greater than 150 °. Highly hydrophobic surfaces with high water repellency generally have biomimetic self-cleaning properties, and in some cases have antimicrobial properties because they do not retain moisture. Therefore, when the hydrophobic cellulosic material obtained using this functionalization method is a fabric, it can be used to make protective clothing. As used herein, the term "protective clothing" refers to waterproof clothing, personal protective clothing, soldier uniforms and work clothes, and coats, laboratory coats, trousers, jackets, aprons, coveralls and part of the body single use or single use accessories, such as hoods, boots or shoe covers, sleeves, gloves and any other clothing items that can be used to cover at least a portion of the body. Protective clothing can be used to avoid any unnecessary contact with hazardous materials and minimize the risk of exposure. When the hydrophobic cellulose material obtained using this functionalization method is paper, it can be applied to the development of disposable laboratory ware and paper-based laboratory devices (e.g., reservoirs for liquid storage and manipulation, funnels, tips for pipettes, or accordion-like substrates for liquid transport or mixing), paper-based electronics industry (e.g., for the development of electronic sensors and chips), or medical and healthcare industries.

[0114] 2. Cellulose-supported catalyst

[0115] Supported catalysts are widely used to accelerate the rates of chemical reactions in various applications. In recent decades, the focus of science and technology is shifting towards environmentally friendly and sustainable resources and processes. Therefore, polysaccharides derived from natural sources that exhibit unique structures and functional groups have recently attracted increasing attention due to their potential applicability as catalyst supports. Several biopolymers, such as alginate, gelatin, starch, chitosan, and cellulose have been used as supports for catalytic applications.

[0116] Thus, in certain embodiments, the functionalization method according to the present invention can be used to functionalize a cellulosic material with a catalytic agent. The method is particularly suitable for heterogeneity of transition metal complexes that are widely used as homogeneous catalysts in organic synthesis. The heterogeneity of homogeneous catalytic complexes combines the advantages of heterogeneous catalysts (good stability and easy recycling that allows "green" catalysis) with the advantages of their homogeneous counterparts (high activity and selectivity). In certain embodiments, the functionalization method according to the present invention is used to functionalize a cellulosic material with a catalyst in the form of a transition metal complex. In other embodiments, the functionalization method according to the present invention is used to functionalize a cellulosic material with a ligand; then, the transition metal is complexed with the ligand grafted on the cellulosic material so that the metal-ligand complex forms a catalytic agent.

[0117] Transition metal-ligand complexes that can be used as catalysts in the practice of the present invention are known in the art. As used herein, the term "transition metal" refers to any transition metal known to be used in the preparation of transition metal organometallic complex catalysts. The most commonly used are titanium, vanadium, chromium, manganese, iron, cobalt, nickel, zirconium, molybdenum, ruthenium, rhodium, palladium, tantalum, osmium and iridium. As used herein in the context of catalysts, the term "ligand" refers to a molecule that binds to a metal atom to form a coordination complex. Bonding to the metal typically includes the form of one or more ligand electron pairs. In the context of the present invention, the ligand can be selected from ligands known to bind to transition metal atoms to form catalysts. Examples of suitable ligands include, but are not limited to, N-heterocyclic carbene (NHC) ligands (e.g., NHC imidazolidine ligands, NHC imidazole ligands, NHC thiazole ligands, NHC triazole ligands); BINOL (1,1'-bis-2-naphthol) and TADDOL (α,α,α',α',-tetraaryl-2,2-disubstituted 1,3-dioxolane-4,5-dimethanol) ligands; phosphines (e.g., dialkyl-phosphinobiphenylphosphines, amino- and imino-phosphines, neomenthyl-diphenyl-phosphine), phosphites (e.g., triorganophosphites, diorganophosphites, bisphosphites); ethyleneimine ligands (e.g., ethylenediaminetetraacetic acid, tetraethylenepentamine), poly(hydroxamic acid) ligands, and the like.

[0118] 3. Other uses

[0119] Those skilled in the art will recognize that the functionalization methods described herein can be used to functionalize cellulosic materials with any of a variety of other functional groups, such as for enzyme immobilization, biosensing, diagnostics, water filtration, remediation, anti-counterfeiting, covalent printing, and the like.

[0120] A. Water Filtration and Remediation

[0121] As described above, the functionalization methods described herein can be used to introduce metal ligands on cellulose materials. For example, cellulose filter paper can be functionalized with ethylenediaminetetraacetic acid (EDTA), a chelating agent, to treat samples containing various heavy metal cations, including Ag(I), Pb(II), Cd(II), Ni(II), Zn(II), Sn(II), and Cu(II) (d'Halliun et al., ACS Sustainable Chem. Eng., 2017, 5: 1965-1973). Other examples of chelating agents include, but are not limited to, [4-(1,4,8,11-tetraazacyclotetradec-1-yl)methyl]benzoic acid (CPTA), cyclohexanediaminetetraacetic acid (CDTA), ethylene glycol bis(2-aminoethyl ether)tetraacetic acid (EGTA), diethylenetriaminepentaacetic acid (DTPA), citric acid, hydroxyethylethylenediaminetriacetic acid (HEDTA), iminodiacetic acid (IDA), triethylenetetraaminehexaacetic acid (TTHA), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra(methylphosphonic acid) (DOTP), 1,4,8,11-tetraazacyclododecane-1,4,8,11-tetraacetic acid (TETA), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), and derivatives thereof.

[0122] Alternatively, the functionalization method can be used to functionalize the cellulose material with a reagent having specific target binding activity, such as an antibody (or fragment thereof), an antibody mimetic compound (e.g., affibodies, affimers, and Kunitz domains), an aptamer, or any other selective binding polypeptide. The functionalization method can also be used to functionalize the cellulose material with sensor functions, such as detecting nucleic acids, viruses, micropollutants, or high-value products.

[0123] Another example of sensor functionality includes quinine for adsorbing heavy metals such as Cd(II) in water (Aka et al., J. Environ. Sci., 2019, 84: 174-183); ethylenediamine or spermine for adsorbing heavy metals (Nongbe et al., Cellulose, 2018, 25: 4043-4055).

[0124] Cellulose paper functionalized with metal ligands or another specific ligand can have many uses, including filtration, adsorption and water treatment. In particular, such paper membranes can be used to filter liquids to remove micropollutants, such as heavy metals, radionuclides, environmental pollutants, toxins, antimicrobial agents (particularly antibiotics) or hormones that destroy estrogen. In addition, such membranes can be used for the remediation of high-value products (such as gold and heavy metals) in waste streams or in the environment. Alternatively, paper membranes can be used for the specific capture of high-value products in the biotechnology industry, such as the recapture of pharmaceutical products, biological products or catalytic compounds for reuse.

[0125] It is also contemplated that the functionalized cellulosic materials may be used in kidney or liver dialysis applications, to remove toxins from blood or other body fluids ex vivo or in vitro.

[0126] B. Sensing, Biosensing, and Diagnostics

[0127] The functionalization methods described herein can be used to introduce sensing moieties or diagnostic agents on cellulose materials. The terms "sensing moiety," "sensor function," and "sensing agent" are used interchangeably herein and refer to molecules or biochemical molecules or fragments thereof that are capable of specifically interacting or binding with a target analyte in a sample. The interaction and / or binding between the sensing moiety and the target analyte can be direct or indirect. For example, the sensing moiety can be bound to the target analyte via a cross-linking agent. In certain embodiments, the binding between the sensing moiety and the analyte provides one or more detectable signals.

[0128] Sensing moieties are known in the art. Examples of sensing moieties (or sensor functions) have been described above. Other examples of sensing moieties include, but are not limited to, thioglycolic acid, which, when covalently bound to cellulose paper, can reduce Cu (II) in a few seconds and form dark complexes on cellulose paper, thereby detecting copper in water samples (Rull-Barrull et al., Chem. Commun., 2016, 52: 6569-6572), and heptyl mannose (Cauwel et al., Chem. Commun., 2019, 55: 10158-10165) reportedly available for binding and specific detection of pathogenic Escherichia coli. Other examples of suitable sensing agents include antimicrobial peptides (AMPs). Antimicrobial peptides are a group of biomolecules that evolve to identify and kill target microorganisms by binding to cell membranes and destroying cell membranes. Several unique features of antimicrobial peptides make them attractive alternatives to antibodies for detecting microbial biothreats: resistance to proteases, stability to extreme environments, high affinity, overlapping (but not identical) binding reactions with microbial membranes and membrane components. Antimicrobial peptide arrays have been used to detect and classify microbial pathogens with similar or higher sensitivity than antibody-based assays; their broad-spectrum binding activity also provides the potential for detecting unknown (or unsuspected) microorganisms. Another example is a rhodamine-based sensor that, when covalently bound to cellulose paper, constitutes a portable, recyclable and highly selective paper-based sensor device for colorimetric and optical detection of bisulfate anions in water (Rull-Barrull et al., Chem. Comm., 2016, 52: 2525-2528).

[0129] As used herein, the term "diagnostic agent" refers to a sensing moiety used in a method for detecting a target analyte in a biological sample obtained from a subject, wherein the presence of the target analyte in the biological sample indicates the presence and / or progression of a disease or medical condition in the subject.

[0130] Examples of diagnostic agents include, but are not limited to, agents that specifically bind to cells (e.g., one or more specific types of cells that indicate a specific disease and / or a specific state of a cell, tissue, and / or subject), nucleic acids (e.g., DNA, RNA, or modified derivatives thereof), proteins (e.g., extracellular proteins, receptors, tumor markers, transmembrane proteins, enzymes, antibodies), carbohydrates (e.g., monosaccharides, disaccharides, or polysaccharides). In certain embodiments, the diagnostic agent may be a small molecule mimetic of a target ligand (e.g., a peptide mimetic ligand), a target ligand (e.g., a peptide containing an RGD peptide or folate), or an antibody or antibody fragment specific for a specific target. In some embodiments, the diagnostic agent is an aptamer designed to associate or bind to a target of interest.

[0131] C. Covalent Printing

[0132] Paper remains the main material for applications such as packaging, labels and banknote manufacturing. In these applications, the commonly used printing techniques (especially by inkjet) do not provide an adequate level of protection against counterfeiting (i.e., counterfeiting of banknotes and securities, and imitation of items such as clothing, handbags, watches, etc.). Covalent printing differs from the inkjet printing method in that small molecules are covalently attached to cellulose. This technology can achieve a higher level of security by providing a label with increased stability.

[0133] Thus, the methods described herein can be used to functionalize a cellulosic material (e.g., paper or fabric) with a printing agent (i.e., a group that acts as an ink). The method provides a cellulosic material functionalized with a printing agent covalently bonded to the cellulose, i.e., in a more stable manner than those proposed in the prior art. As used herein, the term "printing agent" refers to a compound that produces a visually or spectrally detectable mark. The printing agent may be detectable at a wavelength corresponding to the visible domain (400-700nm), the ultraviolet (UV) domain (200-400nm), or the infrared (IR) domain (700nm-1mm, typically the near infrared (NIR) domain (700-2500nm)), or it may be detectable under the action of a stimulus, such as a change in polarity or a change in pH or a change in temperature. When the printing agent is a photoactive agent, it may be selected from a fluorophore, a chromophore, or a photochromophore.

[0134] Examples of fluorophores include, but are not limited to, xanthene derivatives (e.g., fluorescein, rhodamine, Oregon green, eosin, and Texas red); cyanine derivatives (e.g., cyanine, indocarbocyanine, oxacarbocyanine, thiocarbocyanine, and merocyanine); squaric acid derivatives and ring-substituted squaric acids; naphthalene derivatives (e.g., dansyl and puromycin derivatives); coumarin derivatives; oxadiazole derivatives (e.g., pyridyloxazole, nitrobenzoxadiazole, and benzoxadiazole); anthracene derivatives (e.g., anthraquinone); pyrene derivatives (e.g., Cascade Blue, etc.); oxazine derivatives (e.g., Nile Red, Nile Blue, Cresyl Violet, Oxazine 170, etc.); acridine derivatives (e.g., proflavine, acridine orange, acridine yellow, etc.); arylmethine derivatives (e.g., auramine, crystal violet, malachite green); tetrapyrrole derivatives (e.g., porphyrin, phthalocyanine, bilirubin, etc.).

[0135] Other examples of luminescent compounds include, but are not limited to, polycyclic aromatic compounds such as those containing perylene diimide rings (known as peri-dinaphthalene bis-di imide, perylene or dibenzo[a,h]anthracene); linear conjugated systems such as polyparaphenylene / arylene; planar benzene systems such as rubrene, coumarin dyes; and metal organic compounds containing iridium (Ir), boron (B), aluminum (Al) or platinum (Pt) (e.g., BODIY, i.e., dipyrromethene-boron; Alq3, i.e., tris(8-hydroxyquinoline)aluminum) and other metals such as Ru and Cu.

[0136] The inorganic luminescent compound can be composed of rare earth-doped metal oxide nanoparticles (for example, zirconium oxide, yttrium oxide, zinc oxide, copper oxide, lanthanum oxide, gadolinium oxide, praseodymium oxide, etc. and combinations thereof, which are doped with rare earths, such as lanthanum, cerium, praseodymium, neodymium, samarium, erbium, gadolinium, terbium, dysprosium, holmium, erbium and combinations thereof); metal nanoparticles (for example, gold, silver, platinum, palladium, iridium, rhenium, mercury, ruthenium, osmium, copper, nickel and combinations thereof); semiconductor nanoparticles, such as semiconductors of Group II-VI, Group III-V, Group IV, Group I-VIII, their alloys and mixtures (for example, ternary or quaternary mixtures) and combinations thereof.

[0137] In certain embodiments, the printing agent is a photochromic entity (see, e.g., Bretel et al., ACS Appl. Polym. Mater., 2019, 1(5): 1240-1250). The terms "photochromic entity" and "photochromic motif" are used interchangeably herein and refer to a molecule that can be reversibly converted between two states or isomers A and B having different absorption spectra, the conversion being induced in one or both directions by absorbing electromagnetic radiation. The resulting spectral changes are usually, but not necessarily, visible changes in color. The terms "on" and "off" are sometimes used to refer to the two directions of the photochromic reaction, and the photochromic molecules are then referred to as "photoswitches" or "molecular switches". Suitable photochromic entities may be selected from the group consisting of diarylethenes (particularly dithienylethenes), spiropyrans, spirooxines, fulgides, fulgimides, stilbenes, aromatic azo compounds (particularly azobenzenes, aminoazobenzenes and pseudostilbenes), polycyclic quinones, benzopyrans, naphthopyrans, spirodihydroindolizines, pyrrolidine spiro-cyclohexadienones, viologens, triarylmethanes and anils.

[0138] Cellulosic materials functionalized with printing agents using the method according to the invention can be used as security elements or used to manufacture security elements. As used herein, the term "security element" refers to any element that can be applied to an article, incorporated into an article, or even used to manufacture an article to enable identification or authentication of the article and / or to protect the article from counterfeiting, forgery or counterfeiting. Examples of security elements include, but are not limited to, security belts, strips or tapes; security sheets; security papers; security panels; security patches; security labels and security transfers.

[0139] For example, cellulose paper functionalized with a printing agent can be used to make items of trust (e.g., banknotes, bank checks, traveler's checks, bank cards, credit cards and other payment cards, stocks, bonds, etc.), official documents (e.g., diplomas, certificates of ownership, registration documents, etc.), identifiers (e.g., customer or loyalty cards, health cards, smart cards, company identifiers, membership identifiers, service cards, reservation cards, etc.), transportation tickets, access cards, lottery tickets, tickets for cultural or sporting events, fiscal stamps, labels for brand authentication, tamper-proof labels, seals, etc.

[0140] Cellulose fabrics functionalized with printing agents can be used to make labels for product identification and brand authentication.

[0141] D. Other functional groups

[0142] The functionalization methods described herein can be used to functionalize cellulosic materials with natural or synthetic phenols known to impart antioxidant and / or antimicrobial properties.Antioxidant and antimicrobial properties of paper are of interest, for example, from a food preservation standpoint.

[0143] Cellulosic materials functionalized using the methods of the present invention, particularly functionalized cellulose fabrics, can be used in wound dressings, including dressings with moisturizing properties, having anti-inflammatory or pro-healing ligands attached as functionalizing agents, which can be used to improve the body's own immune and healing responses.

[0144] Controlling the adverse effects of microorganisms on textiles is becoming an important problem, particularly in the medical textile industry. Therefore, in order to protect users from contamination by microorganisms, it is essential to impart antimicrobial activity to textile materials. Another aspect of the antimicrobial functionalization of textiles is to increase the therapeutic value of the material, for example for wound healing. Therefore, the functionalization method according to the invention can be used for functionalizing cellulose fabrics with an antimicrobial agent, which is for example selected from the group consisting of inorganic salts, organometallic compounds, iodophors (substances that slowly release iodine), phenols and thiophenols, antibiotics, heterocycles with anionic groups, nitro compounds, ureas, formaldehyde derivatives and amines. DETAILED DESCRIPTION

[0145] The present invention is further illustrated by the following examples.

[0146] Example

[0147] The following examples describe some preferred modes for preparing and implementing the present invention. However, it should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. In addition, unless the description in the examples is presented in the past tense, the text is not intended to indicate that an experiment was actually performed or data was actually obtained.

[0148] Example 1

[0149] Materials and methods

[0150] Methods. A pristine cellulose fabric chemically functionalized with a diazo compound 1 (ethyl 2-cyano-2-diazoacetate) was chosen as a benchmark reaction to optimize the grafting level (LG) by variation of the experimental conditions. In the standard procedure, a piece of fabric (30 mg, about 1 cm2) immersed in a solution of Rh2(OAc)4 (1 mol%) was treated with a solution of ethyl 2-cyano-2-diazoacetate 1 (3-9 equivalents / glucose unit). 2 ). After the desired grafting time, the fabric pieces were thoroughly washed with ethanol (EtOH), acetone and dichloromethane (DCM) to remove any unreacted diazonium 1 and residual rhodium complexes and stored under argon. The same protocol was used for cellulose paper, except that the cellulose paper was previously subjected to an activation (mercerization) step in aqueous NaOH solution to obtain mercerized paper. In addition, after preparation, the functionalized paper was dried by the action of a nitrogen stream and stored under argon.

[0151] The grafting level was evaluated by elemental analysis. Screening of different solvents (dichloromethane (CH2Cl2), dichloroethane (ClCH2CH2Cl), acetonitrile (CH3CN), benzene (C6H5) and toluene (C6H5-CH3)) was initially performed at room temperature and reflux conditions for 1 hour using Rh2(OAc)4 as catalyst and 3 equivalents of the diazo compound 1.

[0152] When the functionalization process is carried out in the presence of photochemical activation, the reaction mixture is irradiated with an irradiation source of the desired wavelength for the entire duration of the functionalization reaction.

[0153] Results and discussion

[0154] Diazo compounds are a class of highly reactive compounds with the following general formula:

[0155] R 1 R 2 C=N2.

[0156] They are considered to be carbenes or metal carbene equivalents after N2 release (Regitz et al., Diazo Compounds: Properies and Synthesis. Elsevier: 1986). In addition to diazomethane, aliphatic diazo compounds (where R 1 and R 2 are alkyl groups) are rarely explored in synthesis because they are generally too unstable and may explode (Hecht et al., Tetrahedron Lett., 1973, 14: 1397-1400). In contrast, the electron-withdrawing substituents (where R 1 and R 2 Stable diazo compounds (independently selected from ketones, esters, nitriles, sulfones, phosphonates and aromatic rings) can be safely handled and even purified by chromatography (Hock et al., Chem. Eur. J., 2018, 24: 10571-10583). Stable diazo compounds are very attractive and popular reagents because they show a wide range of reactivity and, as carbene equivalents, they tend to insert into C-H or X-H bonds (where X is Si, N, S or O) (Ye et al., Chem. Rev., 1994, 94: 1091-1160; Davies et al., Chem. Rev., 2003, 103: 2861-2904; Zhang et al., Tetrahedron, 2008, 64: 6577-6605; Doyle et al., Chem. Rev., 2010, 110: 704-724; Ford et al., Chem. Rev., 2015, 115: 9981-10080; Ciszewski et al., Org. Biomol. Chem., 2019, 17: 432-448). In the context of green chemistry, the use of diazo compounds offers many benefits. Indeed, transformations using diazo compounds are often associated with simple experimental conditions, do not require additives (such as bases or ligands), and N2 is the only released byproduct.

[0157] The results are shown in Table 1.

[0158] Screening reactions of different solvents were performed at room temperature and reflux for 1 hour using Rh2(OAc)4 as catalyst and 3 equivalents of diazo compound 1. No significant differences were observed from the set of 5 solvents selected for their compatibility with the diazo compound.

[0159] In general, grafting occurs slightly better under reflux conditions, regardless of the solvent used. Under reflux conditions, toluene proved to be the most suitable solvent, since after 1 hour at 100°C a grafting level (LG) of 12.5% ​​was reached, meaning that on average 1 alcohol function was grafted per 8 glucose units.

[0160] Increasing the reaction time from 1 hour to 2 hours did not change the LG (see entries 11-12 of Table 1). Interestingly, significant levels of grafting occurred after only 1 minute (6%), and the LG increased only slightly after 10 minutes of contact.

[0161] Table 1. Optimization of covalent grafting of cellulose (in the form of fabric) with diazo compound 1.

[0162]

[0163] Finally, the number of equivalents of diazo compound 1 per glucose unit used in the process was also varied, but decreasing from 3 to 1 equivalent, or increasing from 3 to 9 equivalents did not improve the grafting level.

[0164] Effect of diazo compounds. After optimizing the experimental conditions using diazo compound 1, several diazo compounds were used to graft onto the cellulose backbone:

[0165]

[0166] The results obtained show several interesting features. First, regardless of the diazo compound used, good grafting levels ranging from 7% to 14% were obtained. These values ​​are within the ideal range to introduce significant modifications of the physical properties of the cellulosic material without compromising its physical integrity and strength. The inventors recently showed that grafting levels exceeding 25% significantly weakened the cellulosic material due to the loss of fiber cohesion, ultimately leading to the dissolution of cellulose in organic solvents (Nongbe et al., Cellulose, 2018, 25: 1395-1411). Secondly, many functional groups such as ketones, nitriles, esters and amides were well tolerated, allowing subsequent functionalization. Third, the cellulose functionalization reaction works well in the absence of diazo compounds with electron-withdrawing groups such as ketones and nitriles. For example, 4,5-diazafluorene moieties can be effectively grafted onto cellulose (Cell-4). This result opens up interesting prospects for the preparation of new ligands. For example, the ability of Cell-4 as a palladium ligand was demonstrated by the preparation of the composite Cell-5 (see Figure 2 ).

[0167]

[0168] Photochemical activation was used instead of rhodium catalysis. Cellulose grafting tests were performed using diazo compound 1 on 100% cellulose paper or fabric, where photochemical activation was used instead of rhodium catalysis, and the other parameters remained the same (toluene was used as solvent, 1 equivalent of diazo compound 1 was used, and the reaction was carried out at 25°C). The results are shown in Table 2.

[0169] Table 2. Functionalization reactions of cellulose with diazo compound 1 in the absence of rhodium catalysis but with (entries 1-6) or without (entry 7) photochemical activation.

[0170]

[0171] The effect of the irradiation wavelength on the grafting rate was quite negligible. Paper and fabric reacted very similarly and resulted in comparable grafting levels. The grafting level was optimal at 15 minutes. Even more surprisingly, the reaction was observed to operate in the absence of light (and rhodium (II) catalyst).

[0172] Example 2

[0173] In order to provide biodegradable and / or recyclable materials that are biocompatible, diazo hydrophobic inks were obtained from bio-based products and considered safe enough for the body. Three compounds were selected as raw materials for the preparation of diazo hydrophobic inks. These three compounds belong to three different families: saturated fatty acids and related compounds, diterpenes and sterols (see Figure 3 ).

[0174] From these natural compounds, synthetic strategies have been developed to produce diazohydrophobic inks.

[0175] This strategy is presented in the scheme below.

[0176]

[0177] Three diazo hydrophobic inks were synthesized according to this strategy, and the overall yield measured for the synthesis of each compound is shown in Table 3 below.

[0178] Table 3. Overall synthetic yields for each of the three diazo hydrophobic inks.

[0179]

[0180] After preparation, each diazo hydrophobic ink was subjected to a grafting reaction on cellulose according to an OH insertion strategy. As shown in the following reaction scheme, the grafting reaction involves cellulose, a diazo compound (hydrophobic ink) and a base to "activate" the cellulose (mercerization).

[0181]

[0182] The characteristics of the different grafting reactions performed are shown in Table 4 below.

[0183] Table 4. Overall synthetic yields for each of the three diazo hydrophobic inks.

[0184]

[0185] Figure 4 The pictures presented in (A), 4(B), and 4(C) show the hydrophobicity of cellulose materials grafted with diazo compounds obtained from cholesterol, palmitic acid, and rosin acid, respectively.

Claims

1. A method for functionalizing a cellulosic material, wherein The following steps are involved: contacting the cellulosic material with a diazo compound to obtain a functionalized cellulosic material, Wherein, the diazo compound has one of the following formulas: Therein the functionalization is carried out in the absence of any photochemical activation.

2. The method of claim 1, wherein the cellulosic material is a mercerized cellulosic material.

3. The method according to any one of claims 1 or 2, wherein the functionalization occurs via the formation of ether bonds.

4. The method according to any one of claims 1 or 2, wherein the cellulosic material is in the form of fabric, paper.

5. The method of any one of claims 1 or 2, wherein the cellulosic material comprises virgin cellulose.

6. The method according to any one of claims 1 or 2, wherein the cellulosic material consists of virgin cellulose.

7. The method according to any one of claims 1 or 2, wherein the functionalization is carried out in a solvent selected from the group consisting of a non-polar solvent, a polar aprotic solvent, and any combination thereof.

8. The method according to any one of claims 1 or 2, wherein the functionalization is carried out at a temperature from room temperature to reflux temperature.

9. The process according to any one of claims 1 or 2, wherein the functionalization takes place in the presence of a rhodium (II) carboxylate used as catalyst.

10. The method according to any one of claims 1 or 2, wherein the functionalization is performed in the absence of a catalyst.

11. Use of the method according to any one of claims 1 to 10 for functionalizing a cellulosic material with a functional group selected from the group consisting of a hydrophobic agent, a catalyst, a sensor, a diagnostic agent, a printing agent, a chelating agent, a ligand, an antioxidant, an antimicrobial agent and a drug, wherein the diazo compound carries the desired functional group; or wherein the diazo compound carries a reactive moiety and the functional group is attached to the functionalized cellulosic material via the reactive moiety.

12. The use according to claim 11, wherein the hydrophobic agent belongs to the saturated fatty acid, diterpene family or sterol family.

13. The use according to claim 12, wherein the hydrophobic agent is selected from the group consisting of cholesterol, palmitic acid and abietic acid.

14. Use of the method according to any one of claims 1 to 10 for producing one of the following: a packaging material or a security element.

15. Use of the method according to any one of claims 1 to 10 for the manufacture of one of the following: a hydrophobic cellulosic material or a cellulose supported catalyst.

16. Functionalized cellulosic material obtained using the method according to any one of claims 1 to 10.

17. Use of the functionalized cellulose material according to claim 16 in packaging, catalysis, filtration, adsorption and water treatment, remediation, medicine, anti-counterfeiting, paper-based electronic devices or in the manufacture of clothing, health care materials, medical devices, trust products, official documents or logos.

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