Patent Description:
Lignocellulose biomass is a highly abundant and potentially low cost renewable feedstock to produce heat, power, fuels, chemicals and materials as an alternative for fossil resources (<NPL>; <NPL>).

Lignocellulose is composed of three main constituents, cellulose, hemicellulose and lignin. Until recently, lignocellulose biorefineries have mainly focused on the valorization of (hemi)cellulose, while lignin was regarded as a side product and mostly used as energy source (by burning) (<NPL>). Only a minor amount of lignin is used for material applications (dispersants, emulsifiers,. ) or in the production of chemicals like vanillin (<NPL>; <NPL>).

There is however a growing consensus that lignin valorization is essential to the environmental sustainability and economics of a lignocellulosic biorefinery (<NPL>). Lignin constitutes the largest direct source of renewable aromatic/phenolic compounds on Earth and is regarded as a promising feedstock for a wide variety of bulk and fine chemicals, as well as fuels.

The most important lignin depolymerization methods are pyrolysis, base-catalyzed depolymerization, hydrogenolysis, liquid-phase reforming, chemical oxidation and gasification, usually yielding moderate amounts (< <NUM> wt%) of numerous monomeric compounds (<NPL>). Very promising routes for lignin depolymerization are reductive methods like hydrogenolysis and liquid-phase reforming, resulting in phenolic monomer-yields up to <NUM> wt% (<NPL>; <NPL>;<NPL>;<NPL>; <NPL>). The phenolic compounds obtained from these processes possess unique chemical structure features. The phenolic entity bears one or two methoxy groups, next to a <NUM>-alkyl chain. Use of such <NUM>-alkylguaiacols (<NUM>-alkyl-<NUM>-methoxyphenols) and <NUM>-alkylsyringols (<NUM>-alkyl-<NUM>,<NUM>-dimethoxyphenols) as intermediates for high-value target chemicals and polymer building blocks has thus far received only little attention. Until now, main research goals have focused on upgrading the lignin-derived compounds to hydrocarbon fuels or aromatics by complete removal of oxygen through hydrodeoxygenation (HDO).

A possible processing of the phenolic compounds into useful products is its conversion into alternative bisphenols (i.e. m,m'-bis(<NUM>-alkylphenol) derivatives), which maintain both the methoxy group(s) in ortho position, and an alkyl moiety in para position with respect to the phenolic hydroxyl group. As a tangential benefit, alternative bisphenols may have significantly lower toxicity than typical precursors of bisphenol A. However, a challenge remains the production of highly pure m,m'-bis(<NUM>-alkylphenol) derivatives, since commercial bisphenols, like bisphenol A, are typically required in high purity (≥<NUM> wt%) for polycondensation reactions towards polycarbonates (<CIT>). This polycarbonate is known for its superior high-performance properties, including a high transparency, high colour stability, low colour and good melt stability. Moreover, thermoplastic compositions including this polycarbonate resulted in materials with a good impact strength (<CIT>) and flame retardancy (<CIT>). Development of alternatives to existing polycarbonates that maintain properties are of great interest for both the plastics and manufacturing industry. Hence, alternative high-purity bisphenols are necessary to produce polymeric materials with the desirable properties.

Next, the state-of-the-art concerning the synthesis and purification of m,m'-bis(<NUM>-alkylphenol) derivatives is summarized and ordered chronologically.

To initiate a model study of the relationship between structure and antioxidant activity (Pospíšil et al. , <NUM>, <NUM>, <NUM>-<NUM>) <NPL> prepared a broad collection of methylenebisphenols. Among these also <NUM>-methylphenols (like <NUM>-methoxy-<NUM>-methylphenol, <NUM>-ethoxy-<NUM>-methylphenol and <NUM>-methyl-<NUM>,<NUM>-benzenediol) were used. Thereto, a stoichiometric amount of paraformaldehyde was added to a solution of the phenol in formic acid (<NUM> in <NUM> acid) and the mixture heated at <NUM> for <NUM> minutes. The isolated products, being <NUM>,<NUM>'-methylenebis(<NUM>-methoxy-<NUM>-methylphenol), <NUM>,<NUM>'-methylenebis(<NUM>-ethoxy-<NUM>-methylphenol) and <NUM>,<NUM>'-methylenebis(<NUM>-methyl-<NUM>,<NUM>-benzenediol), were obtained, after purification of the reaction mixture by a combination of extraction, column chromatography (silica gel impregnated with formamide) and repeated crystallization, in <NUM> (benzene-hexane), <NUM> (ethyl acetate-hexane) and <NUM> wt% (ether-benzene), with melting points at <NUM>, <NUM> and <NUM>-<NUM> respectively. Higher unidentified condensation product of the starting phenols <NUM>-methoxy-<NUM>-methylphenol and <NUM>-methyl-<NUM>,<NUM>-benzenediol were isolated in only <NUM> wt% and <NUM> wt% only. The multi-step purification, with the need for column chromatography, limits an industrial implementation. Moreover, the use of controversial solvents like benzene and hexane are preferably avoided.

In their study of lignin model compounds<NPL> coupled creosol (i.e. <NUM>-methoxy-<NUM>-methylphenol) with formaldehyde in 2N HCl/dioxane and also obtained <NUM>,<NUM>'-methylenebis(<NUM>-methoxy-<NUM>-methylphenol). Thin layer chromatography revealed that higher condensation products were present only in small amounts. The isolated product was obtained in <<NUM> wt% only after purification of the reaction mixture (being a brown powder) by column chromatography (silica gel/benzene). Recrystallizations of the pure product from benzene eventually gave crystals with a melting point around <NUM>-<NUM>. Said process is unwanted for above mentioned reasons.

<NPL> treated different arylglycerol-β-aryl ethers, as main structural unit in lignin, with <NUM>% H<NUM>SO<NUM>, which resulted in the formation of <NUM>,<NUM>'-methylenebis(<NUM>-methoxy-<NUM>-methylphenol). These results indicated that formation of diarylmethane structures occur during the hydrolysis of wood or lignin with H<NUM>SO<NUM>. Besides ia ortho,meta'-coupled dimer (i.e. <NUM>-(<NUM>-hydroxy-<NUM>-methoxy-<NUM>-methylbenzyl)-<NUM>-methoxy-<NUM>-methylphenol).

In order to elucidate the behavior of syringylglycerol-β-syringyl ether as a main structural unit in angiosperm lignin under the influence of sulfuric acid, <NPL> treated phenolic and non-phenolic model compounds in dilute (<NUM>%) and concentrated sulfuric acid (<NUM>%). Reaction of both non-phenolic and phenolic syringylglycerol-β-syringyl ether in both <NUM>% and <NUM>% sulfuric acid yielded <NUM>,<NUM>'-methylenebis(<NUM>,<NUM>-dimethoxy-<NUM>-methylphenol). The isolated product was obtained in <NUM>-<NUM> wt% after purification of the product mixture by column chromatography (on silica gel with n-hexane/acetone). The compound melted around <NUM>-<NUM>. The formation of this dimer suggests elimination of the hydroxymethyl group as formaldehyde to some extent, which undergoes acid-promoted condensation with liberated and/or added <NUM>,<NUM>-dimethoxy-<NUM>-methylphenol. Said process is unwanted for above mentioned reasons.

<CIT> reacted <NUM>-methylcatechol with an aldehyde in the presence of an acid catalyst to form <NUM>,<NUM>'-methylenebis(<NUM>-methyl-<NUM>,<NUM>-benzenediol). High purity biscatechol was prepared in high yield, and the biscatechol was useful for positive working photoresist. No details about purification procedure can be found.

<NPL> reported a series of renewable bisphenols synthesized from creosol through stoichiometric condensation with short shain aldehydes (like formaldehyde, acetaldehyde and propionaldehyde) in aqueous acidic (i.e. HCl, HBr) media. The isolated products, being <NUM>,<NUM>'-methylenebis(<NUM>-methoxy-<NUM>-methylphenol), <NUM>,<NUM>'-(ethane-<NUM>,<NUM>-diyl)bis(<NUM>-methoxy-<NUM>-methylphenol) and <NUM>,<NUM>'-(propane-<NUM>,<NUM>-diyl)bis(<NUM>-methoxy-<NUM>-methylphenol), were obtained as white solids in only <NUM>, <NUM> and <NUM> wt% respectively, after dissolving in ether and precipitating with heptane. The first two compounds melted around <NUM>-<NUM> and <NUM>-<NUM>. Although ortho,meta'-isomers were detected, no details were given on their fate during precipitation. Neither a report is given on the formation of higher condensation products (i.e. oligomers, such as trimers). Subsequently, <NPL> converted these bisphenols to a series of renewable bis(cyanate) esters (in <NUM>-<NUM> wt%) with applications in a wide variety of military and commercial applications. The bisphenols can also be applied in organic thin film transistors having solution-processed n-type copolymers as the semiconductor material (<CIT>).

<NPL> also performed the synthesis of creosol-based bisphenols in water. Lignosulfonic acid (<NUM> mol%), a byproduct of the paper industry, was demonstrated to be an efficient and green catalyst in water for this stoichiometric condensation of creosol with formaldehyde. The isolated product, being <NUM>,<NUM>'-methylenebis(<NUM>-methoxy-<NUM>-methylphenol), was obtained in only <NUM> wt% after purification of the reaction products by column chromatography (petroleum ether/ethyl acetate = <NUM>:<NUM>) and melted at <NUM>-<NUM>. Also the o,m'-isomer and a trimeric species were isolated (in <NUM> wt% and <NUM> wt% respectively) and characterized for the first time. Hereafter, this bisphenol was converted into polycarbonates (in <NUM>% yield) and polyurethanes by polyaddition of bis(cyclic carbonate) and diamines (<NPL>).

Van der<NPL> describe the synthesis of <NUM>,<NUM>'-methylenebis(<NUM>-ethyl-<NUM>-methoxyphenol) and <NUM>,<NUM>'-methylenebis(<NUM>-ethyl-<NUM>,<NUM>-dimethoxyphenol) from respectively <NUM>-ethyl-<NUM>-methoxyphenol and <NUM>-ethyl-<NUM>,<NUM>-dimethoxyphenol with <NUM> fold excess formaldehyde in <NUM> HCl in <NUM> % aqueous dioxane at ambient temperature for <NUM> and <NUM> respectively. The isolated products were obtained in only <NUM> wt% and <NUM> wt% respectively after purification of the crude product by flash chromatography (silica gel with hexane/ethyl acetate = <NUM>:<NUM>). Besides the main product, in the case of the guaiacyl analog, also mono-hydroxymethylated monomers (<NUM> wt%) and dimers (<NUM> wt%), and trimers (<NUM> wt%) were isolated. In the case of the syringyl analog, considerable amounts of trimers (<NUM> wt%) formed. When the same reactions were performed with an equimolar quantity of formaldehyde in <NUM> HCl in <NUM>% aqueous dioxane at <NUM> a maximum yield of <NUM> % and <NUM> % (as determined by HPLC) were reached within <NUM>-<NUM> and <NUM>-<NUM> respectively. In these conditions, considerable amount of higher condensation products (tri-, tetra- and oligomers) were observed in the case of the syringyl analog. The same chemistry yields lignin meta-hydroxyalkyl derivatives by treating lignin with a reagent (e.g. an aldehyde) in an acid medium in the presence of an organic solvent. The substituted lignin may be reacted with a nucleophile. Thus, alkali lignin from different industrial origins reacted with formaldehyde in <NUM>% aqueous dioxane under acidic conditions at positions <NUM>- and <NUM>- gave methylene crosslinks which resulted in the formation of a polymeric product, whereas using <NUM>% aqueous dioxane and <NUM>-1N HCl, meta-hydroxymethylation was the preferential reaction (<NPL>; <CIT>).

From the above-mentioned state-of-the-art, based on the literature melting points reported for identical compounds, one skilled in the art can conclude that residual impurities often remain, as for example in the case of <NUM>,<NUM>'-methylenebis(<NUM>-methoxy-<NUM>-methylphenol).

Hence, there is a great incentive to produce high-purity m,m'-coupled bis(<NUM>-alkylguaiacol) and bis(<NUM>-alkylsyringol) derivatives in high purity (and yield) which can be easily purified from the reaction product mixture containing residual substrate, (m,m'- and o,m'-)dimers and oligomeric by-products/impurities, without the need for solvent-intense methods like column/flash chromatography and the use of controversial solvents (like hexane, benzene and dioxane).

The present invention provides such production of m,m'-bis(<NUM>-alkylguaiacol) and m,m'-bis(<NUM>-alkylsyringol) derivatives in high product yield (<NUM>-<NUM> wt%) which is purified from the raw reaction product mixture containing residual substrate, and isomeric (i.e. o,m'-product) and/or oligomeric by-products/impurities with high purity of ≥<NUM> % of m,m'-coupled bis(<NUM>-alkylguaiacol) or bis(<NUM>-alkylsyringol) derivative by wt. of the end-product, more preferably ≥<NUM> % of m,m'-coupled bis(<NUM>-alkylguaiacol) and bis(<NUM>-alkylsyringol) derivative by wt. of the end-product as analysed by melting point measurement (by differential scanning calorimetry), gas chromatography and/or gel-permeation/size-exclusion chromatography.

The present invention anticipates on the future utilization of various <NUM>-alkylphenol derivatives (e.g. <NUM>-methoxy-<NUM>-n-propylphenol and <NUM>,<NUM>-dimethoxy-<NUM>-n-propylphenol) for synthesis of alternative bisphenols. These <NUM>-alkylphenol derivatives can be obtained from, among other, the depolymerisation of lignin enclosed in lignocellulosic biomass.

From raw reaction product mixtures in which condensation reactions of <NUM>-alkyl-<NUM>-alkoxyphenols (e.g. <NUM>-methoxy-<NUM>-n-propylphenol) or <NUM>-alkyl-<NUM>,<NUM>-dialkoxyphenols (e.g. <NUM>,<NUM>-dimethoxy-<NUM>-n-propylphenol) have occurred, m,m'-coupled bis(<NUM>-alkylphenol) derivatives are selectively crystallized in high purity of at least <NUM> % of m,m'-bis(<NUM>-alkylphenol) by wt. of the end-product.

The process of the present invention is useful for the production of high-purity m,m'-coupled bis(<NUM>-alkylguaiacol) and/or bis(<NUM>-alkylsyringol), in which the alkyl substituent is for instance methyl, ethyl or n-propyl.

According to the present invention, there is provided a process for the production of aromatic dihydroxy compounds of ><NUM> wt% purity, as defined in claim <NUM>. Optional features of the invention are defined in dependent claims <NUM>-<NUM>.

The accompanying figures, which are incorporated in and constitute a part of this specification, illustrate several aspects and together with the description serve to explain the principles of the invention.

The present disclosure can be understood more readily by reference to the following detailed description of the disclosure and the EXAMPLES include therein.

Before the present compounds, compositions, articles, systems, devices, and/or methods are disclosed and described, it is to be understood that they are not limited to specific synthetic methods unless otherwise specified, or to particular reagents unless otherwise specified, as such can, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only and is not intended to be limiting. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing the present disclosure, example methods and materials are now described.

Moreover, it is to be understood that unless otherwise expressly stated, it is in no way intended that any method set forth herein be construed as requiring that its steps be performed in a specific order. Accordingly, where a method claim does not actually recite an order to be followed by its steps or it is not otherwise specifically stated in the claims or descriptions that the steps are to be limited to a specific order, it is no way intended that an order be inferred, in any respect. This holds for any possible non-express basis for interpretation, including: matters of logic with respect to arrangement of steps or operational flow; plain meaning derived from grammatical organization or punctuation; and the number or type of embodiments described in the specification.

It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only and is not intended to be limiting. As used in the specification and in the claims, the term "comprising" can include the aspects "consisting of" and "consisting essentially of". In this specification and in the claims which follow, reference will be made to a number of terms which shall be defined herein.

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. Thus, for example, reference to "a polymer" includes mixtures of two or more polymers.

As used herein, the term "combination" is inclusive of blends, mixtures, alloys, reaction products, and the like.

Ranges can be expressed herein as from one particular value, and/or to another particular value. Similarly, when values are expressed as approximations, by use of the antecedent 'about,' it will be understood that the particular value forms another aspect. It is also understood that there are a number of values disclosed herein, and that each value is also herein disclosed as "about" that particular value in addition to the value itself.

As used herein, the terms "about" and "at or about" mean that the amount or value in question can be the value designated some other value approximately or about the same. It is generally understood, as used herein, that it is the nominal value indicated ±<NUM>% variation unless otherwise indicated or inferred. The term is intended to convey that similar values promote equivalent results or effects recited in the claims. That is, it is understood that amounts, sizes, formulations, parameters, and other quantities and characteristics are not and need not be exact, but can be approximate and/or larger or smaller, as desired, reflecting tolerances, conversion factors, rounding off, measurement error and the like, and other factors known to those of skill in the art. In general, an amount, size, formulation, parameter or other quantity or characteristic is "about" or "approximate" whether or not expressly stated to be such. It is understood that where "about" is used before a quantitative value, the parameter also includes the specific quantitative value itself, unless specifically stated otherwise.

As used herein, the terms "optional" or "optionally" means that the subsequently described event or circumstance can or cannot occur, and that the description includes instances where said event or circumstance occurs and instances where it does not. For example, the phrase "optionally substituted alkyl" means that the alkyl group can or cannot be substituted and that the description includes both substituted and unsubstituted alkyl groups.

As used herein, the term "effective amount" refers to an amount that is sufficient to achieve the desired modification of a physical property of the composition or material. For example, an "effective amount" of a filler refers to an amount that is sufficient to achieve the desired improvement in the property modulated by the formulation component, e.g. achieving the desired level of modulus. The specific level in terms of wt % in a composition required as an effective amount will depend upon a variety of factors including the amount and type of polycarbonates, amount and type of thermally conductive filler, and use of the article made using the composition.

Disclosed are the components to be used to prepare the compositions of the invention as well as the compositions themselves to be used within the methods disclosed herein. These and other materials are disclosed herein, and it is understood that when combinations, subsets, interactions, groups, etc. of these materials are disclosed that while specific reference of each various individual and collective combinations and permutation of these compounds cannot be explicitly disclosed, each is specifically contemplated and described herein. For example, if a particular compound is disclosed and discussed and a number of modifications that can be made to a number of molecules including the compounds are discussed, specifically contemplated is each and every combination and permutation of the compound and the modifications that are possible unless specifically indicated to the contrary. Thus, if a class of molecules A, B, and C are disclosed as well as a class of molecules D, E, and F and an example of a combination molecule, A-D is disclosed, then even if each is not individually recited each is individually and collectively contemplated meaning combinations, A-E, A-F, B-D, B-E, B-F, C-D, C-E, and C-F are considered disclosed. Likewise, any subset or combination of these is also disclosed. Thus, for example, the sub-group of A-E, B-F, and C-E would be considered disclosed. This concept applies to all aspects of this application including, but not limited to, steps in methods of making and using the compositions of the disclosure. Thus, if there are a variety of additional steps that can be performed it is understood that each of these additional steps can be performed with any specific aspect or combination of aspects of the methods of the disclosure.

References in the specification and concluding claims to parts by weight of a particular element or component in a composition or article, denotes the weight relationship between the element or component and any other elements or components in the composition or article for which a part by weight is expressed. Thus, in a compound containing <NUM> parts by weight of component X and <NUM> parts by weight component Y, X and Y are present at a weight ratio of <NUM>:<NUM>, and are present in such ratio regardless of whether additional components are contained in the compound.

As used herein the terms "weight percent," "wt %," and "wt. %," which can be used interchangeably, indicate the percent by weight of a given component based on the total weight of the composition, unless otherwise specified. That is, unless otherwise specified, all wt % values are based on the total weight of the composition. It should be understood that the sum of wt % values for all components in a disclosed composition or formulation are equal to <NUM>.

For example, any position not substituted by any indicated group is understood to have its valence filled by a bond as indicated, or a hydrogen atom. Unless defined otherwise, technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which this disclosure belongs.

The term "alkyl group" as used herein is a branched or unbranched saturated hydrocarbon group of <NUM> to <NUM> carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, pentyl, hexyl, heptyl, octyl, decyl, tetradecyl, hexadecyl, eicosyl, tetracosyl and the like. A "lower alkyl" group is an alkyl group containing from one to six carbon atoms.

The term "aryl group" as used herein is any carbon-based aromatic group including, but not limited to, benzene, naphthalene, etc. The term "aromatic" also includes "heteroaryl group," which is defined as an aromatic group that has at least one heteroatom incorporated within the ring of the aromatic group. Examples of heteroatoms include, but are not limited to, nitrogen, oxygen, sulphur, and phosphorus. The aryl group can be substituted or unsubstituted. The aryl group can be substituted with one or more groups including, but not limited to, alkyl, alkynyl, alkenyl, aryl, halide, nitro, amino, ester, ketone, aldehyde, hydroxy, carboxylic acid, or alkoxy.

The term "aralkyl" as used herein is an aryl group having an alkyl, alkynyl, or alkenyl group as defined above attached to the aromatic group. An example of an aralkyl group is a benzyl group.

The term "organic residue" defines a carbon containing residue, i.e., a residue comprising at least one carbon atom, and includes but is not limited to the carbon-containing groups, residues, or radicals defined hereinabove. Organic residues can contain various heteroatoms, or be bonded to another molecule through a heteroatom, including oxygen, nitrogen, sulphur, phosphorus, or the like. Examples of organic residues include but are not limited to alkyl or substituted alkyls, alkoxy or substituted alkoxy, mono or di-substituted amino, amide groups, etc. Organic residues can preferably comprise <NUM>-<NUM> carbon atoms, <NUM>-<NUM> carbon atoms, <NUM>-<NUM> carbon atoms, <NUM>-<NUM> carbon atoms, <NUM>-<NUM> carbon atoms, or <NUM>-<NUM> carbon atoms. In a further aspect, an organic residue can comprise <NUM>-<NUM> carbon atoms, <NUM>-<NUM> carbon atoms, <NUM>-<NUM> carbon atoms, <NUM>-<NUM> carbon atoms, <NUM>-<NUM> carbon atoms, or <NUM>-<NUM> carbon atoms.

A very close synonym of the term "residue" is the term "radical", which as used in the specification and concluding claims, refers to a fragment, group, or substructure of a molecule described herein, regardless of how the molecule is prepared. For example, a <NUM>,<NUM>-dihydroxyphenyl radical in a particular compound has the structure:
<CHM>
regardless of whether <NUM>,<NUM>-dihydroxyphenyl is used to prepare the compound. In some aspects the radical (for example an alkyl) can be further modified (i.e., substituted alkyl) by having bonded thereto one or more "substituted radicals". The number of atoms in a given radical is not critical to the present disclosure unless it is indicated to the contrary elsewhere herein.

"Organic radicals", as the term is defined and used herein, contain one or more carbon atoms. An organic radical can have, for example, <NUM>-<NUM> carbon atoms, <NUM>-<NUM> carbon atoms, <NUM>-<NUM> carbon atoms, <NUM>-<NUM> carbon atoms, <NUM>-<NUM> carbon atoms, or <NUM>-<NUM> carbon atoms. In a further aspect, an organic residue can comprise <NUM>-<NUM> carbon atoms, <NUM>-<NUM> carbon atoms, <NUM>-<NUM> carbon atoms, <NUM>-<NUM> carbon atoms, <NUM>-<NUM> carbon atoms, or <NUM>-<NUM> carbon atoms. Organic radicals often have hydrogen bound to at least some of the carbon atoms of the organic radical. One example, of an organic radical that comprises no inorganic atoms is a <NUM>,<NUM>,<NUM>,<NUM>-tetrahydro-<NUM>-naphtyl radical. In some aspects, an organic radical can contain <NUM>-<NUM> inorganic heteroatoms bound thereto or therein, including halogens, oxygen, sulphur, nitrogen, phosphorus, and the like. Examples of organic radicals include but are not limited to an alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, mono-substituted amino, di-substituted amino, acyloxy, cyano, carboxy, carboalkoxy, alkylcarboxamide, substituted alkylcarboxamide, dialkylcarboxamide, substituted dialkylcarboxamide, alkylsulfonyl, alkylsulfinyl, thioalkyl, thiohaloalkyl, alkoxy, substituted alkoxy, haloalkyl, haloalkoxy, aryl, substituted aryl, heteroaryl, heterocyclic, or substituted heterocyclic radicals, wherein the terms are defined elsewhere herein. A few nonlimiting examples of organic radicals that include heteroatoms include alkoxy radicals, trifluoromethoxy radicals, acetoxy radicals, dimethylamino radicals and the like.

As used herein, "polycarbonate" refers to an oligomer or polymer comprising residues of one or more dihydroxy compounds, e.g., dihydroxy aromatic compounds, joined by carbonate linkages; it also encompasses homopolycarbonates, copolycarbonates and (co)polyester carbonates.

The terms "residues" and "structural units", used in reference to the constituents of the polymers, are synonymous throughout the specification.

As used herein, "product yield" is defined as the molar amount of product formed per molar amount of starting substrate and "substrate conversion" is defined as the molar amount of substrate converted per molar amount of starting material. "product selectivity" is defined as the ratio of the product yield over the substrate conversion. For instance a particular embodiment context "conversion" means the mole percent of the initial <NUM>-alkylphenol derivative that is reacted to form a different compound, not necessarily all the desired product, while "yield" is the mole percent of the converted starting material that forms any bis(<NUM>-alkylphenol) derivative and "selectivity" is the mole percent of the reaction product formed that is bis(<NUM>-alkylphenol) derivative. For example, if <NUM> moles of <NUM>-alkylphenol derivative are reacted and <NUM> moles of <NUM>-alkylphenol derivative are left unchanged, then the conversion is <NUM> percent. If the reaction product contains <NUM> moles of bis(<NUM>-alkylphenol) derivative then the yield is <NUM> percent and the selectivity is <NUM> percent.

Each of the materials disclosed herein are either commercially available and/or the methods for the production thereof are known to those of skill in the art.

In accordance with the purpose(s) of the disclosure, as embodied and broadly described herein, the disclosure, in one aspect, relates to meta,meta'-coupled bis(<NUM>-alkylphenol) derivatives which are valuable precursors for renewable thermoplastics, (high temperature) resins/thermosets, bio-derived C15-C19 fuel additives, antioxidants, UV-stabilizers, plasticizers, soluble n-type perylene copolymers and/or positive working photoresists.

In various aspects, the present disclosure relates to a process for purification of meta,meta'-coupled bis(<NUM>-alkylphenol) derivatives in high purity. The terms "meta,meta'-coupled bis(<NUM>-alkylphenol) derivatives", "m,m'-coupled bis(<NUM>-alkylphenol) derivatives", "m,m'-bis(<NUM>-alkylphenol) derivatives", "m,m'-coupled dimers" and "m,m'-dimers" which can be used interchangeably, as used herein refers to a compound having a structure represented by the formula:
<CHM>.

In various aspects, m,m'-bis(<NUM>-alkylphenol) derivatives are defined as structures comprising two phenolic units coupled by a one atom bridging group (-X-) connecting the two hydroxyl-substituted aromatic groups selected from oxy (-O-), thio (-S-), sulfinyl (-S(O)-), sulfonyl (-S(O)<NUM>-), carbonyl (-C(O)-), or a alkanediyl C1-C24 organic group; and wherein the bridging group (-X-) and the hydroxyl substituent are disposed meta to each other on the arylene group bearing the phenolic (Ar-OH) functionality; and wherein the alkyl chain (-CH<NUM>R) and the hydroxyl substituent are disposed para to each other on the arylene group bearing the phenolic (Ar-OH) functionality; and wherein at least one alkoxy group (Ar-OR and/or Ar-R) is disposed ortho to the arylene groups bearing the phenolic (Ar-OH) functionality.

In various aspects, this general class of monomers is known as aromatic dihydroxy compounds.

As used herein, "raw reaction product mixture" concerns the rough, crude, non-fractionated, mixed, complex organic phase resulting from the condensation reaction of the <NUM>-alkylphenol derivative, without prior purification steps (such as column chromatography, extraction, and the like). The raw reaction product mixture contains at least residual substrate, dimers and oligomers.

As used herein, "condensation reaction" is defined as and comprises: a) providing a <NUM>-alkylphenol derivative; b) providing a carbonylic compound; c) reacting the phenol and carbonylic compound under conditions effective to provide a reaction product comprising a m,m'-coupled bis(<NUM>-alkylphenol) derivative.

In further aspects, conditions effective comprise reacting the <NUM>-alkylphenol derivative and carbonylic compound in the presence of a catalyst. In yet further aspects, the catalyst comprises a strongly acidic catalyst, more preferable a soluble strongly acidic catalyst and even more preferable a water-soluble strongly acidic catalyst. In yet further aspects the water-soluble strongly acidic catalyst comprises a i) hydrohalic acid/hydracid (i.e. hydrochloric, hydrobromic, hydroiodic and/or hydroastatic acid), ii) oxyacid (i.e. nitric, sulphuric and/or perchloric acid) and/or iii) an organic acid, such as (un)halogenated sulfonic acid and halogenated carboxylic acid, and/or mixtures and/or combinations thereof.

In further aspects, the carbonylic compound comprises R(H)(C=O) (i.e. aldehydes), (H)<NUM>(C=O)<NUM> (i.e. glyoxal), (H)(C=O)R(C=O)(H) (i.e. dialdehydes), (H)(C=O)(COOH) (i.e. glyoxylic acid), (H)(C=O)(COOR) (i.e. alkyl glyoxylates), R(R)(C=O) (i.e. ketones), R(R)(C=O)<NUM> (i.e. vicinal diketones), (R)(C=O)(COOH) (i.e. α-keto acids) and/or (R)(C=O)(COOR) (i.e. α-keto esters) with R a C1-C24 organic group. In still further aspects the aldehyde is methanal (i.e. formaldehyde), ethanal (i.e. acetaldehyde), propanal (i.e. propionaldehyde), butanal (i.e. butyraldehyde). In still further aspects, the aldehyde is preferably methanal. In still further aspects the dialdehyde is ethanedial (i.e. glyoxal), propanedial (i.e. malonaldehyde), butanedial (i.e. succinaldehyde), pentanedial (i.e. glutaraldehyde), benzene-<NUM>,<NUM>-carbaldehyde (i.e. phthalaldehyde). In still further aspects the dialdehyde is preferably glyoxal. In still further aspects, the alkyl glyoxalate is methyl glyoxalate, ethyl glyoxalate, propyl glyoxalate. In still further aspects, the alkyl glyoxalate is preferably methyl glyoxalate. In still further aspects the ketone is a methyl ketone, such as acetone, <NUM>-butanone and <NUM>-pentanone. In still further aspects, the ketone is preferably acetone. In still further aspects the vicinal diketone is <NUM>,<NUM>-butanedione, <NUM>,<NUM>-pentanedione, <NUM>,<NUM>-hexanedione or <NUM>,<NUM>-heptanedione. In still further aspects, the vicinal diketone is preferably <NUM>,<NUM>-butanedione. In still further aspects the α-keto acid is pyruvic acid. In still further aspects the α-keto esters is methyl pyruvate.

In further aspects, conditions effective comprise adjusting the temperature to at least about <NUM>. In still further aspects, the temperature is adjusted to a temperature of from <NUM> to about <NUM>, including exemplary temperatures of about <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, and <NUM>.

In further aspects, conditions effective comprise maintaining the reaction for at least about <NUM> hours. In yet further aspects, the reaction is maintained for about <NUM>-<NUM> hours, including exemplary times of <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, and <NUM> hours.

In further aspects, conditions effective comprise a continuous stirring regime i) in which the contact interface between the liquid aqueous phase and the liquid organic phase is maximal and ii) in which homogeneity conditions (like temperature, concentration) are guaranteed as much as possible.

In various aspects, conditions effective comprise a liquid aqueous phase from at least about <NUM> wt. % to about <NUM> wt. % of distilled, de-ionized and/or demineralized water and/or mixtures and/or combinations thereof, including exemplary values of <NUM> wt%, <NUM> wt%, <NUM> wt%, <NUM> wt%, <NUM> wt%, <NUM> wt%, <NUM> wt%, <NUM> wt%, <NUM> wt%, <NUM> wt%, <NUM> wt%, <NUM> wt%, <NUM> wt%, <NUM> wt%, <NUM> wt%, and <NUM> wt%. In yet further aspects the liquid aqueous phase contains a co-solvent(s) in a range from <NUM> - <NUM> wt%, preferably between <NUM>-<NUM> wt%, and even more preferably between <NUM>-<NUM> wt%.

In various aspects, conditions effective comprise the reaction to take place under a (partial) modified or unmodified atmosphere. In some aspects the modified atmosphere comprises the use of inert gasses like nitrogen (N<NUM>), argon (Ar) and/or mixtures and/or combinations thereof.

In some aspects, the <NUM>-alkylphenol derivative is provided as a pure substance to yield symmetric m,m'-bis(<NUM>-alkylphenol) derivatives. In some aspects, the <NUM>-alkylphenol derivative consists of mixtures and/or combinations of <NUM> or more different types to yield asymmetric m,m'-bis(<NUM>-alkylphenol) derivatives.

In various aspects, the <NUM>-alkylphenol derivative and aldehyde or ketone are provided at a molar ratio of at least about <NUM>:<NUM>. In further aspects, the <NUM>-alkylphenol derivative and aldehyde or ketone are provided at a stoichiometric molar ratio of <NUM>:<NUM>.

As used herein, the term "residual substrate" refers to unreacted, unconverted <NUM>-alkylphenol derivatives.

In further aspects, the <NUM>-alkylphenol derivative comprises <NUM>-alkyl-<NUM>-hydroxyphenols (i.e. <NUM>-alkylcatechols such as, <NUM>-hydroxy-<NUM>-methylphenol, <NUM>-ethyl-<NUM>-hydroxyphenol, <NUM>-hydroxy-<NUM>-n-propylphenol, <NUM>-n-butyl-<NUM>-hydroxyphenol, <NUM>-hydroxy-<NUM>-n-pentylphenol), <NUM>-alkoxy-<NUM>-alkylphenols (i.e. <NUM>-alkylguaiacols such as, <NUM>-methoxy-<NUM>-methylphenol, <NUM>-ethyl-<NUM>-methoxyphenol, <NUM>-methoxy-<NUM>-n-propylphenol, <NUM>-n-butyl-<NUM>-methoxyphenol, <NUM>-methoxy-<NUM>-n-pentylphenol and <NUM>-alkylguethols such as, <NUM>-ethoxy-<NUM>-methylphenol, <NUM>-ethoxy-<NUM>-ethylphenol, <NUM>-ethoxy-<NUM>-n-propylphenol, <NUM>-n-butyl-<NUM>-ethoxyphenol, <NUM>-ethoxy-<NUM>-n-pentylphenol), <NUM>-alkyl-<NUM>,<NUM>-dihydroxyphenol or <NUM>-alkylbenzene-<NUM>,<NUM>,<NUM>-triol (i.e. <NUM>-alkylpyrogallol such as, <NUM>-methylbenzene-<NUM>,<NUM>,<NUM>-triol, <NUM>-ethylbenzene-<NUM>,<NUM>,<NUM>-triol, <NUM>-n-propylbenzene-<NUM>,<NUM>,<NUM>-triol, <NUM>-n-butylbenzene-<NUM>,<NUM>,<NUM>-triol, <NUM>-n-pentylbenzene-<NUM>,<NUM>,<NUM>-triol), <NUM>-alkoxy-<NUM>-alkylbenzene-<NUM>,<NUM>-diol (i.e. <NUM>-alkoxy-<NUM>-alkylcatechol such as, <NUM>-methoxy-<NUM>-methylbenzene-<NUM>,<NUM>-diol, <NUM>-ethyl-<NUM>-methoxybenzene-<NUM>,<NUM>-diol, <NUM>-methoxy-<NUM>-n-propylbenzene-<NUM>,<NUM>-diol, <NUM>-n-butyl-<NUM>-methoxybenzene-<NUM>,<NUM>-diol, <NUM>-methoxy-<NUM>-n-pentylbenzene-<NUM>,<NUM>-diol, <NUM>-ethoxy-<NUM>-methylbenzene-<NUM>,<NUM>-diol, <NUM>-ethoxy-<NUM>-ethylbenzene-<NUM>,<NUM>-diol, <NUM>-ethoxy-<NUM>-n-propylbenzene-<NUM>,<NUM>-diol, <NUM>-n-butyl-<NUM>-ethoxybenzene-<NUM>,<NUM>-diol, <NUM>-ethoxy-<NUM>-n-pentylbenzene-<NUM>,<NUM>-diol) and/or <NUM>,<NUM>-dialkoxy-<NUM>-alkylphenols (i.e. <NUM>-alkylsyringol such as, <NUM>,<NUM>-dimethoxy-<NUM>-methylphenol, <NUM>-ethyl-<NUM>,<NUM>-dimethoxyphenol, <NUM>,<NUM>-dimethoxy-<NUM>-n-propylphenol, <NUM>-n-butyl-<NUM>,<NUM>-dimethoxyphenol, <NUM>,<NUM>-dimethoxy-<NUM>-n-pentylphenol, <NUM>,<NUM>-diethoxy-<NUM>-methylphenol, <NUM>,<NUM>-diethoxy-<NUM>-ethylphenol, <NUM>,<NUM>-diethoxy-<NUM>-n-propylphenol, <NUM>-n-butyl-<NUM>,<NUM>-diethoxyphenol, <NUM>,<NUM>-diethoxy-<NUM>-n-pentylphenol).

In various aspects, the raw reaction product mixture contains less than about <NUM> wt% residual substrate, more preferably less than about <NUM> wt% residual substrate and even more preferably less than about <NUM> wt% residual substrate.

As used herein, the terms "dimer", "dimers" and "dimeric" refer to m,m'-coupled dimers, o,m'-coupled dimers and/or o,o'-coupled dimers. The terms "isomer", "isomers" and "isomeric" refer only to o,m'-coupled dimers and/or o,o'-coupled dimers.

In various aspects, the raw reaction product mixture is comprised of at least about <NUM> wt% dimers, more preferably at least about <NUM> wt% dimers and even more preferably at least about <NUM> wt% dimers. In further aspects, the raw reaction product mixture comprise at least about <NUM> wt% m,m'-dimers, more preferably at least about <NUM> wt% m,m'-dimers and even more preferably at least about <NUM> wt% m,m'-dimers. In even further aspects, the raw reaction product mixture comprises less than about <NUM> wt% isomers, more preferably less than about <NUM> wt% isomers and even more preferably less than about <NUM> wt% isomers.

As used herein, the terms "oligomer", "oligomers" and "oligomeric" refer to higher condensation (by)products (such as trimers, tetramers, and the like) originating from consecutive over-condensation (i.e. oligomerisation) of dimers.

In various aspects, the raw reaction product mixture comprises less than about <NUM> wt% isomers, more preferably less than about <NUM> wt% isomers and even more preferably less than about <NUM> wt% isomers.

As used herein, "precipitation" is defined as the sedimentation of a solid material (a precipitate) from a liquid solution in which the material is present in amounts greater than its solubility in the liquid (IUPAC Compendium of Chemical Technology). In general, precipitation is a process which happens (homogeneously) throughout the entire solution rather quickly and results in something opaque, cloudy and/or ill-defined.

As used herein, "crystallisation" is defined as the formation of a crystalline solid from a solution, melt vapour or a different solid phase, generally by the lowering of the temperature or by evaporation of a solvent (IUPAC Compendium of Chemical Technology). In general, crystallisation is a process which happens (heterogeneously) at interface of the solution and container rather slowly and results in something with a defined crystal structure.

As used herein, "high purity" is defined as a purity equal or higher than <NUM> wt%, more preferably equal or higher than <NUM> wt% as analysed by melting point measurement (via differential scanning calorimetry), gas chromatography, gel-permeation/size exclusion chromatography, high-pressure liquid chromatography and/or thermogravimetric analysis, and/or combinations thereof.

As used herein, the term "highly pure meta,meta'-coupled bis(<NUM>-alkylphenol) derivatives" refers to a highly pure meta,meta'-coupled bis(<NUM>-alkylphenol) derivative substantially free of impurity comprising the residual substrate, isomeric and/or oligomeric impurity in an amount of less than about <NUM> area-% as measured by gas chromatography or gel-permeation/size exclusion chromatography. Specifically, the meta,meta'-coupled bis(<NUM>-alkylphenol) derivative as disclosed herein, contains less than about <NUM> area-%, more specifically less than about <NUM> area-%, still more specifically less than about <NUM> area-% of the impurities.

In another embodiment, the highly pure meta,meta'-coupled bis(<NUM>-alkylphenol) derivative disclosed herein has a total purity of greater than about <NUM> wt%, specifically greater than about <NUM> wt%, more specifically greater than about <NUM> wt%, and most specifically greater than about <NUM> wt% as analysed by melting point measurement (via differential scanning calorimetry), gas chromatography, gel-permeation/size exclusion chromatography, high-pressure liquid chromatography and/or thermogravimetric analysis, and/or combinations thereof. For example, the purity of the meta,meta'-coupled bis(<NUM>-alkylphenol) derivative is about <NUM> wt%, to about <NUM> wt%, or about <NUM> wt% to about <NUM> wt%.

In another embodiment, the meta,meta'-coupled bis(<NUM>-alkylphenol) derivative disclosed herein is essentially free of one, or more, of the residual substrate, isomeric or oligomeric impurities. In yet another embodiment, the highly pure meta,meta'-coupled bis(<NUM>-alkylphenol) derivative is for instance a highly pure meta,meta'-coupled bis(<NUM>-alkylguaiacol) or highly pure meta,meta'-coupled bis(<NUM>-alkylsyringol) derivative.

According to the invention, the selective (re)crystallization is a gradual evaporative crystallization process. The selective (re)crystallization is done by using a mixture of non-solvent alkane and solvent.

As used herein, the terms "slow evaporation", "gradual evaporation" and/or "slow gradual evaporation" are defined as an evaporation rate at which the solution of crystallization is maintained at low supersaturation (i.e. conditions in which crystal growth rate exceeds nucleation rate) as indicated by the optical transparency of this solution. Exceeding this specific evaporation rate will result in an opaque, cloudy and non-optical transparent solution (cf. precipitation).

As used herein, the terms "solution of crystallization" and "solution of raw reaction product mixture" are defined and can be used interchangeably as the solvent and/or anti-solvent system in which the raw reaction product mixture is dissolved.

Without further elaboration, it is believed that one skilled in the art can, using the description herein, utilize the present disclosure.

While aspects of the present disclosure can be described and claimed in a particular statutory class, such as the system statutory class, this is for convenience only and one of skill in the art will understand that each aspect of the present disclosure can be described and claimed in any statutory class. Unless otherwise expressly stated, it is in no way intended that any method or aspect set forth herein be construed as requiring that its steps be performed in a specific order. Accordingly, where a method claim does not specifically state in the claims or descriptions that the steps are to be limited to a specific order, it is no way intended that an order be inferred, in any respect. This holds for any possible non-express basis for interpretation, including matters of logic with respect to arrangement of steps or operational flow, plain meaning derived from grammatical organization or punctuation, or the number or type of aspects described in the specification.

In various aspect the disclosed highly pure bis(<NUM>-alkylphenols) derivatives are valuable precursors for making renewable thermoplastics, (high temperature) resins/thermosets, bio-derived C<NUM>-C<NUM>fuel additives, antioxidants, UV-stabilizers, plasticizers, soluble n-type perylene copolymers and/or positive working photoresists.

In some aspects, these highly pure bis(<NUM>-alkylphenol) derivative, being a polyphenol, is converted into a thermoplastic and/or (high temperature) resin/thermoset composition which comprises the bis(<NUM>-alkylphenol) derivative, a polyphenol co-monomer, and/or mixtures and/or combinations thereof. Other aspects of the invention further include composites.

Further aspects include converting the polyphenols by reaction with reagents including phosgene, diphosgene (DP), triphosgene (TP), carbonyldiimidazole (CDI), disuccinimidyl carbonate (DSC), diphenylcarbonate, other carbonates, bis(<NUM>-chlorophenyl) sulfone, other functionalized sulfones, diacid chlorides, phtalic acids, formaldehyde, other aldehydes, (meth)acryloyl chloride or (meth)acrylic anhydride, dialkoxy methane and epichlorohydrin to produce thermoplastics or thermosetting resins selected from the group consisting of polycarbonates, polyiminocarbonates, polyurethanes, polysulfones (PSf), polyether sulfones (PESf), polyether ether ketones (PEEK), polyester, polyester-styrene polymers, polyacetals, alkylphenolics, polyarylates, cyanate ester resins, epoxy resins, benzoxazine resins, phenolic resins, bismaleimide resins, polyphenylene resins, vinyl ester resins and other endcapped resins (high temperature thermosetting resins) and any combination thereof.

In embodiments, thermosetting resins are combined with the thermoplastics or resins, fiber, or other support materials and are thermally cured either with or without a catalyst to fabricate composite materials.

In some aspects, these bis(<NUM>-alkylphenol) derivatives can undergo hydrodeoxygenation (HDO) to produce C<NUM>-C<NUM> fuel additives which can be introduced into the heavy fuel fraction in diesel (C<NUM>-C<NUM>) to improve physicochemical properties and/or serve as a renewable carbon source (<NPL>).

In some aspects, these bis(<NUM>-alkylphenol) derivatives can be employed as antioxidants, UV-stabilizers and/or plasticizers, and/or mixtures and/or combinations thereof. The phenolic OH group plays a vital role toward imparting antioxidant characteristics, such as stabilization of polyolefins, like polyethylene and isotactic polypropylene (Pospíšil et al. , <NUM>, <NUM>, <NUM>-<NUM>), due to the potent scavenging activity on aggressive OH radicals and the efficient H-atom donor properties inducing free radical quenching (<NPL>; <NPL>; <NPL>).

In some aspects, these bis(<NUM>-alkylphenol) derivatives can be employed as positive working photoresist and/or photographic material (<CIT> <CIT>).

In some aspects, these bis(<NUM>-alkylphenol) derivatives can be applied in organic thin film transistors having solution-processed n-type copolymers as the semi-conductor material. The bio-derived bis(<NUM>-alkylphenol) comonomers have flexible solubilizing groups that aid in solubilizing the resulting perylene copolymers and in forming planarizing films of these copolymers (<CIT>).

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

There are numerous variations and combinations of reaction conditions, e.g., component concentrations, desired solvents, solvent mixtures, temperatures, pressures and other reaction ranges and conditions that can be used to optimize the product purity and yield obtained from the described process. Only reasonable and routine experimentation will be required to optimize such process conditions.

All materials and reagents were used as received from the supplier unless otherwise indicated. All chemicals were A. grade and other sources can be used besides the ones indicated below.

Analysing mixtures of structurally resembling monomers, dimers and higher oligomers is not straightforward. Thereto, gas chromatography (GC) and gel permeation/size exclusion chromatography (GPC/SEC) were adapted for this analysis and compared. Due to a high chemical similarity among the reagent and products, the dimer yield and monomer conversion can only be measured accurately by GC. Due to the limited volatility of (derivatized) higher oligomers in GC, additional GPC/SEC measurements were performed to confirm their absence/presence.

GC analysis was performed on a Hewlett-Packard (HP) <NUM> with a CP-SIL 5CB WCOT fused silica column (<NUM> x <NUM>, film thickness of <NUM>), equipped with an FID detector (<NUM>) and ChemStation software. The injection port and initial oven temperatures were <NUM> and <NUM> respectively. This temperature was held for <NUM>, increased to <NUM> at <NUM>. min-<NUM>, and held there for <NUM>. Prior to GC analysis, the samples were derivatized via trimethylsilylation with N-methyl-N-(trimethylsilyl) trifluoroacetamide (MSTFA). In a typical sample preparation, the dried organic phase (<NUM>), together with <NUM> guaiacol (Sigma-Aldrich, ≥<NUM> %; standard 1a) or syringol (Sigma-Aldrich, ><NUM> %; standard 1b) and <NUM> <NUM>,<NUM>'-methylenediphenol (TCI Europe, ><NUM> %; standard <NUM>) as external standards, were accurately weighed in a glass vial and homogeneously mixed with <NUM>µL of anhydrous pyridine (Sigma-Aldrich, <NUM>%) and <NUM>µL. of MSTFA (Sigma-Aldrich, ≥<NUM> %). To guarantee a complete derivatization with MSTFA, the samples were heated for <NUM> at <NUM> and subsequently diluted with <NUM> acetonitrile (Acros, <NUM>+ %). One µl of the sample was injected at a split ratio of <NUM>:<NUM>. This GC methodology allows to separate m,m'-, o,m'-and o,o'-isomers and gives an indication of the presence of higher oligomers (e.g. trimers) which only partially evaporate. Quantification of mono- and dimers was performed by calibration of the pure (isolated) reagent/product against the applied external standards.

Idendification of dimeric GC signals was accomplished by gas chromatography-mass spectrometry (GC-MS) on a Agilent <NUM> series with a HP1-MS capillary column equipped with an Agilent <NUM> series mass spectroscopy detector (El, <NUM> eV ionisation energy).

To get more insight into the presence, type and (relative) amount of higher oligomers, the distribution of the molar mass of the dried organic phase was investigated using GPC/SEC. Therefore, a sample was solubilized in THF (~<NUM>. mL-<NUM>; Sigma-Aldrich, ><NUM>%) and subsequently filtered with a <NUM> PTFE membrane to remove any particulate matter to prevent plugging of the columns. GPC/SEC analysis was performed on a Waters e2695 Separations Module with a pre-column and a Varian M-Gel column (<NUM>, mixed), equipped with a Waters <NUM> Photodiode array detector (UV detection at <NUM>), Empower software and using THF as the mobile phase (<NUM>. min-<NUM> ) at <NUM>. Together with GC, melting point determination and thermogravimetric analysis (TGA), this GPC/SEC analysis was conducted as a means to validate the purity (i.e. absence of higher oligomers). In contrast to <NUM>H-NMR, which provides a number-average oligomer length, GPC/SEC analysis allows to distinguish all oligomers encountered.

Liquid-phase <NUM>H and <NUM>C nuclear magnetic resonance (NMR) spectra were acquired on Bruker Avance instruments (<NUM> and <NUM>) with automated samplers. The chemical shifts (δ) are reported in parts per million (ppm) referenced to tetramethylsilane (<NUM>H) or the internal NMR solvent signals (<NUM>C). In a typical sample preparation, a dried sample (~<NUM> for <NUM>H and ~<NUM> for <NUM>C) is homogeneously dissolved in <NUM>-<NUM>µL of deuterated chloroform (CDCl<NUM> and transferred to a NMR tube. Fourier-transform infrared (FT-IR) spectra of dried KBr pellets, premixed with pure product (<NUM> wt%), were recorded in vacuo on a Bruker IFS 66v/S instrument.

TGA was performed while heating under N<NUM> atmosphere using a TA Instruments TGA Q500. About <NUM> of the dried sample was heated at <NUM>. min-<NUM> to <NUM> and kept isothermal for <NUM> at a flow rate of <NUM>. Melting points (Tm) of the crystals were determined using sealed glass capillaries in a Stuart Scientific SMP3 melting point apparatus and confirmed by differential scanning calorimetry (DSC) on a TA Instruments DSC Q2000 by cycling between <NUM> and <NUM> at heating/cooling rates of <NUM>. min-<NUM> under N<NUM> atmosphere.

<NUM> (<NUM> mmol) <NUM>-methoxy-<NUM>-methylphenol (Sigma-Aldrich, ≥<NUM>%), <NUM> (<NUM> mmol) formaldehyde (Sigma-Aldrich, <NUM> wt%) and <NUM> (<NUM> in H<NUM>O) concentrated HCl (Fisher Scientific, <NUM> wt%) were placed in a <NUM> Duran® laboratory bottle with screw cap, as well as a magnetic stirring bar (<NUM>). At the start of the reaction, the closed bottle is partially (<NUM>/<NUM>) submerged in a pre-heated stirred temperature-controlled oil bath. The bath is held at <NUM> under continuous stirring (<NUM> rpm) for <NUM> hours. Once back at room temperature, the aqueous acidic phase was decanted, the yellowish-green organic (solid) phase dissolved in anhydrous acetone (Sigma-Aldrich, ≥<NUM> %) and dried with anhydrous MgSO<NUM> (Sigma-Aldrich, ≥<NUM> %). After filtration of the dried organic phase, n-heptane was carefully added as non-solvent until the solution comes close to the point of supersaturation, but without inducing precipitation. Crystallization of <NUM>,<NUM>'-methylenebis(<NUM>-methoxy-<NUM>-methylphenol) was induced by gradual evaporation of a transparent acetone/n-heptane solution. Highly pure (≥<NUM> %) crystals were harvested by filtration and dried in vacuo (<NUM>, ~<NUM> mbar) overnight (see <FIG>, <FIG>, <FIG> and <FIG>). The mother liquor was left enriched with residual substrate, isomers and oligomers.

Yield: <NUM> (<NUM> %). (powder) <NUM>-<NUM>; m. (crystals) <NUM>; <NUM>H NMR (<NUM>, CDCl<NUM>, <NUM>, TMS): δH = <NUM> (s, <NUM>; -ArCH<NUM>), <NUM> (s, <NUM>; -ArCH<NUM>Ar-), <NUM> (s, <NUM>; -OCH<NUM>), <NUM> (s, <NUM>; -ArOH), <NUM> (s, <NUM>; -o-ArH), <NUM> ppm (s, <NUM>; -m-ArH); <NUM>C NMR (<NUM>, CDCl<NUM>, <NUM>, TMS): δC = <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> and <NUM> ppm; MS (<NUM> eV, El): m/z (%): <NUM> (<NUM>) [M+•+•H], <NUM> (<NUM>) [M+•], <NUM> (<NUM>) [M+•-•CH<NUM>], <NUM> (<NUM>) [M+•-•C<NUM>H<NUM>O<NUM>], <NUM> (<NUM>) [M+•-C<NUM>H<NUM>O<NUM>]; FTIR (KBr): ṽmax = <NUM> (C-O), <NUM> (C-O), <NUM> (C-O), <NUM> (C-O), <NUM> (arom. C=C), <NUM> (aliph. C-H), <NUM> (aliph. C-H), <NUM> (arom. C-H), <NUM> (arom. C-H), <NUM> (arom. C-H), <NUM> (polymeric O-H) and <NUM>-<NUM> (monomeric O-H).

<NUM> (<NUM> mmol) <NUM>-ethyl-<NUM>-methoxy-phenol (Sigma-Aldrich, ≥<NUM>%), <NUM> (<NUM> mmol) formaldehyde (Sigma-Aldrich, <NUM> wt%) and <NUM> (<NUM> in H<NUM>O) concentrated HCl (Fisher Scientific, <NUM> wt%) were placed in a <NUM> Duran® laboratory bottle with screw cap, as well as a magnetic stirring bar (<NUM>). At the start of the reaction, the closed bottle is partially (<NUM>/<NUM>) submerged in a pre-heated stirred temperature-controlled oil bath. The bath is held at <NUM> under continuous stirring (<NUM> rpm) for <NUM> hours. Once back at room temperature, the aqueous acidic phase was decanted, the yellowish-orange organic (oily) phase dissolved in anhydrous diethyl ether (Sigma-Aldrich, ≥<NUM> %) and dried with anhydrous MgSO<NUM> (Sigma-Aldrich, ≥<NUM> %). After filtration of the dried organic phase, n-heptane was carefully added as non-solvent until the solution comes close to the point of supersaturation, but without inducing precipitation. Crystallization of <NUM>,<NUM>'-methylenebis(<NUM>-ethyl-<NUM>-methoxyphenol) was induced by gradual evaporation of a transparent diethyl ether/n-heptane solution. Highly pure (≥<NUM> %) crystals were harvested by filtration and dried in vacuo (<NUM>, ~<NUM> mbar) overnight (see <FIG>, <FIG>, <FIG> and <FIG>). The mother liquor was left enriched with residual substrate, isomers and oligomers.

Yield: <NUM> (<NUM> %). (powder) <NUM>-<NUM>; m. (crystals) <NUM>-<NUM>; <NUM>H NMR (<NUM>, CDCl<NUM>, <NUM>, TMS): δH = <NUM> (t, <NUM>J(H,H)= <NUM>, <NUM>; -CH<NUM>CH<NUM>), <NUM> (q, <NUM>J(H,H)= <NUM>, <NUM>; - CH<NUM>CH<NUM>), <NUM> (s, <NUM>; -ArCH<NUM>Ar-), <NUM> (s, <NUM>; -OCH<NUM>), <NUM> (s, <NUM>; -ArOH), <NUM> (s, <NUM>; -o-ArH), <NUM> ppm (s, <NUM>; -m-ArH); <NUM>C NMR (<NUM>, CDCl<NUM>, <NUM>, TMS): δC = <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> and <NUM> ppm; MS (<NUM> eV, El): m/z (%): <NUM> (<NUM>) [M+•+•H], <NUM> (<NUM>) [M+•], <NUM> (<NUM>) [M+•-•C<NUM>H<NUM>], <NUM> (<NUM>) [M+•-•C<NUM>H<NUM>O<NUM>], <NUM> (<NUM>) [M+•-C<NUM>H<NUM>O<NUM>], <NUM> (<NUM>); FTIR (KBr): ṽmax = <NUM> (C-O), <NUM> (C-O), <NUM> (C-O), <NUM> (arom. C=C), <NUM> (aliph. C-H), <NUM> (aliph. C-H), <NUM> (aliph. C-H), <NUM> (aliph. C-H), <NUM> (arom. C-H), <NUM> (polymeric O-H) and <NUM>-<NUM> (monomeric O-H).

<NUM> (<NUM> mmol) <NUM>-methoxy-<NUM>-propylphenol (Sigma-Aldrich, <NUM>+%), <NUM> (<NUM> mmol) formaldehyde (Sigma-Aldrich, <NUM> wt%) and <NUM> (<NUM> in H<NUM>O) concentrated HCl (Fisher Scientific, <NUM> wt%) were placed in a <NUM> Duran® laboratory bottle with screw cap, as well as a magnetic stirring bar (<NUM>). At the start of the reaction, the closed bottle is partially (<NUM>/<NUM>) submerged in a pre-heated stirred temperature-controlled oil bath. The bath is held at <NUM> under continuous stirring (<NUM> rpm) for <NUM> hours. Once back at room temperature, the aqueous acidic phase was decanted, the yellowish-red organic (oily) phase dissolved in anhydrous diethyl ether (Sigma-Aldrich, ≥<NUM> %) and dried with anhydrous MgSO<NUM> (Sigma-Aldrich, ≥<NUM> %). After filtration of dried the organic phase, n-heptane was carefully added as non-solvent until the solution comes close to the point of supersaturation, but without inducing precipitation. Crystallization of <NUM>,<NUM>'-methylenebis(<NUM>-methoxy-<NUM>-n-propylphenol) was induced by gradual evaporation of a transparent diethyl ether/n-heptane solution. Highly pure (≥<NUM> %) crystals were harvested by filtration and dried in vacuo (<NUM>, ~<NUM> mbar) overnight (see <FIG>, <FIG> and <FIG>). The mother liquor was left enriched with residual substrate, isomers and oligomers.

Yield: <NUM> (<NUM> %). (powder) <NUM>-<NUM>; m. (crystals) <NUM>-<NUM>; <NUM>H NMR (<NUM>, CDCl<NUM>, <NUM>, TMS): δH = <NUM> (t, <NUM>J(H,H)= <NUM>, <NUM>; -CH<NUM>CH<NUM>), <NUM> (sex, <NUM>J(H,H)= <NUM>, <NUM>; - CH<NUM>CH<NUM>CH<NUM>), <NUM> (t, <NUM>J(H,H)= <NUM>, <NUM>; -ArCH<NUM>CH<NUM>-), <NUM> (s, <NUM>; -ArCH<NUM>Ar-), <NUM> (s, <NUM>; - OCH<NUM>), <NUM> (bs, <NUM>; -ArOH), <NUM> (s, <NUM>; -o-ArH), <NUM> ppm (s, <NUM>; -m-ArH); <NUM>C NMR (<NUM>, CDCl<NUM>, <NUM>, TMS): δC = <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> and <NUM> ppm; MS (<NUM> eV, El): m/z (%): <NUM> (<NUM>) [M+•+•H], <NUM> (<NUM>) [M+•], <NUM> (<NUM>) [M+•-•C<NUM>H<NUM>], <NUM> (<NUM>) [M+•-•C<NUM>H<NUM>], <NUM> (<NUM>) [M+•-•C<NUM>H<NUM>O<NUM>], <NUM> (<NUM>) [M+•-C<NUM>H<NUM>O<NUM>]; FTIR (KBr): ṽmax = <NUM> (CO), <NUM> (C-O), <NUM> (arom. C=C), <NUM> (aliph. C-H), <NUM> (aliph. C-H), <NUM> (aliph. C-H), <NUM> (aliph. C-H), <NUM> (arom. C-H) and <NUM> (polymeric O-H), <NUM>-<NUM> (monomeric O-H).

<NUM> (<NUM> mmol) <NUM>,<NUM>-dimethoxy-<NUM>-methylphenol (Alfa Aesar, <NUM> %), <NUM> (<NUM> mmol) formaldehyde (Sigma-Aldrich, <NUM> wt%) and <NUM> (<NUM> in H<NUM>O) concentrated HCl (Fisher Scientific, <NUM> wt%) were placed in a <NUM> Duran® laboratory bottle with screw cap, as well as a magnetic stirring bar (<NUM>). At the start of the reaction, the closed bottle is partially (<NUM>/<NUM>) submerged in a pre-heated stirred temperature-controlled oil bath. The bath is held at <NUM> under continuous stirring (<NUM> rpm) for <NUM> hours. Once back at room temperature, the aqueous acidic phase was decanted, the yellowish-white organic (solid) phase dissolved in anhydrous acetone (Sigma-Aldrich, ≥<NUM> %) and dried with anhydrous MgSO<NUM> (Sigma-Aldrich, ≥<NUM> %). After filtration of the dried organic phase, n-heptane was carefully added as non-solvent until the solution comes close to the point of supersaturation, but without inducing precipitation. Crystallization of <NUM>,<NUM>'-methylenebis(<NUM>,<NUM>-dimethoxy-<NUM>-methylphenol) was induced by gradual evaporation of a transparent acetone/n-heptane solution. Highly pure (≥<NUM> %) crystals were harvested by filtration and dried in vacuo (<NUM>, ~<NUM> mbar) overnight (see <FIG>, <FIG> and <FIG>). The mother liquor was left enriched with residual substrate and oligomers.

Yield: <NUM> (<NUM> %). (powder) <NUM>-<NUM>; m. (crystals) <NUM>; <NUM>H NMR (<NUM>, CDCl<NUM>, <NUM>, TMS): δH = <NUM> (s, <NUM>; -ArCH<NUM>), <NUM> (s, <NUM>; -<NUM>-OCH<NUM>), <NUM> (s, <NUM>; -<NUM>-OCH<NUM>), <NUM> (s, <NUM>; -ArCH<NUM>Ar-), <NUM> (s, <NUM>; -ArOH), <NUM> ppm (s, <NUM>; -m-ArH); <NUM>C NMR (<NUM>, CDCl<NUM>, <NUM>, TMS): δC = <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> and <NUM> ppm; MS (<NUM> eV, El): m/z (%): <NUM> (<NUM>) [M+•+•H], <NUM> (<NUM>) [M•+], <NUM> (<NUM>) [M+•-•C<NUM>H<NUM>O<NUM>], <NUM> (<NUM>) [M+•-C<NUM>H<NUM>O<NUM>], <NUM> (<NUM>), <NUM> (<NUM>), <NUM> (<NUM>), <NUM> (<NUM>), <NUM> (<NUM>); FTIR (KBr): ṽmax = <NUM> (C-O), <NUM> (C-O), <NUM> (C-O), <NUM> (C-O), <NUM> (arom. C=C), <NUM> (aliph. C-H), <NUM> (aliph. C-H), <NUM> (aliph. C-H), <NUM> (aliph. C-H), <NUM> (aliph. C-H), <NUM> (polymeric O-H) and <NUM>-<NUM> (monomeric O-H).

For the catalytic hydrogenolysis experiment, pre-extracted birch wood chips (<NUM>; particle size <NUM>-<NUM>; <NUM> wt% Klason lignin), catalyst powder (<NUM> Ru/C; Sigma-Aldrich, <NUM> wt%) and methanol (<NUM>; Sigma-Aldrich, ><NUM>%) were loaded into a <NUM> stainless steel batch reactor (Parr Instruments & Co. The reactor was sealed, flushed threefold with N<NUM>, and pressurized with H<NUM> (<NUM> MPa at room temperature). Subsequently, the reaction mixture was stirred (<NUM> rpm) and heated to <NUM> (-<NUM>. min-<NUM>). When the reaction temperature was reached, the temperature was kept constant for <NUM> after which the reactor was cooled and depressurized at room temperature. Afterwards, the reactor contents were quantitatively collected by washing extensively with methanol followed by a filtration step to separate the solid residue (pulp and catalyst) from the liquid product mixture.

After reductive processing, the liquid and solid reactor contents were quantitatively collected and separated from each other over a glass fritted filter. Subsequently, the methanol was evaporated. In this way a light-brown oil was obtained, which was subjected to a threefold liquid-liquid extraction using dichloromethane (DCM; Sigma-Aldrich, ><NUM> %) and water to separate the soluble lignin products from sugar-derived products or other polar components. Finally the DCM-extracted phase was dried to obtain the 'lignin oil' (<NUM> - <NUM>). This lignin oil was subjected to a threefold reflux extraction with n-hexane (Sigma-Aldrich, ≥<NUM>%) and the extract was distilled in vacuo to obtain a transparent yellow oil (<NUM> -<NUM>) rich in <NUM>,<NUM>-dimethoxy-<NUM>-n-propylphenol. The product was further purified by column chromatography (<NUM> % v/v acetone in n-heptane) on silica gel (Sigma-Aldrich, pore size <NUM>Å, <NUM>-<NUM> mesh, <NUM>-<NUM>).

Yield: <NUM> (<NUM> % on lignin basis). <NUM>H NMR (<NUM>, CDCl<NUM>, <NUM>, TMS): δH = <NUM> (t, <NUM>J(H,H)= <NUM>, <NUM>; -CH<NUM>CH<NUM>), <NUM> (sex, <NUM>J(H,H)= <NUM>, <NUM>; -CH<NUM>CH<NUM>CH<NUM>), <NUM> (t, <NUM>J(H,H)= <NUM>, <NUM>; - ArCH<NUM>CH<NUM>-), <NUM> (s, <NUM>; -OCH<NUM>), <NUM> (s, <NUM>; -ArOH) and <NUM> ppm (s, <NUM>; -m-ArH); <NUM>C NMR (<NUM>, CDCl<NUM>, <NUM>, TMS): δC = <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> and <NUM> ppm; MS (<NUM> eV, El): m/z (%): <NUM> (<NUM>) [M+•], <NUM> (<NUM>) [M+•-•CH<NUM>CH<NUM>].

<NUM> (<NUM> mmol) <NUM>,<NUM>-dimethoxy-<NUM>-n-propylphenol (≥<NUM> %), <NUM> (<NUM> mmol) formaldehyde (Sigma-Aldrich, <NUM> wt%) and <NUM> (<NUM> in H<NUM>O) concentrated HCl (Fisher Scientific, <NUM> wt%) were placed in a <NUM> Duran® laboratory bottle with screw cap, as well as a magnetic stirring bar (<NUM>). At the start of the reaction, the closed bottle is partially (<NUM>/<NUM>) submerged in a pre-heated stirred temperature-controlled oil bath. The bath is held at <NUM> under continuous stirring (<NUM> rpm) for <NUM> hours. Once back at room temperature, the aqueous acidic phase was decanted, the orange-red organic (oily) phase dissolved in anhydrous diethyl ether (Sigma-Aldrich, ≥<NUM> %) and dried with anhydrous MgSO<NUM> (Sigma-Aldrich, ≥<NUM> %). After filtration of the dried organic phase, n-heptane was carefully added as non-solvent until the solution comes close to the point of supersaturation, but without inducing precipitation. Crystallization of <NUM>,<NUM>'-methylenebis(<NUM>,<NUM>-dimethoxy-<NUM>-n-propylphenol) was induced by gradual evaporation of a transparent diethyl ether/n-heptane solution. Highly pure (≥<NUM> %) crystals were harvested by filtration and dried in vacuo (<NUM>, ~<NUM> mbar) overnight (see Fig. 1E, <FIG> and <FIG>). The mother liquor was left enriched with residual substrate and oligomers.

Yield: <NUM> (<NUM> %). (powder) <NUM>-<NUM>; m. (crystals) <NUM>-<NUM>; <NUM>H NMR (<NUM>, CDCl<NUM>, <NUM>, TMS): δH = <NUM> (t, <NUM>J(H,H)= <NUM>, <NUM>; -CH<NUM>CH<NUM>), <NUM> (sex, <NUM>J(H,H)= <NUM>, <NUM>; - CH<NUM>CH<NUM>CH<NUM>), <NUM> (t, <NUM>J(H,H)= <NUM>, <NUM>; -ArCH<NUM>CH<NUM>-), <NUM> (s, <NUM>; -<NUM>-OCH<NUM>), <NUM> (s, <NUM>; -<NUM>-OCH<NUM>), <NUM> (s, <NUM>; -ArCH<NUM>Ar-), <NUM> (s, <NUM>; -ArOH), <NUM> ppm (s, <NUM>; -m-ArH); <NUM>C NMR (<NUM>, CDCl<NUM>, <NUM>, TMS): δC = <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> and <NUM> ppm; MS (<NUM> eV, El): m/z (%): <NUM> (<NUM>) [M+•+•H], <NUM> (<NUM>) [M+•], <NUM> (<NUM>) [M+•-•C<NUM>H<NUM>O<NUM>], <NUM> (<NUM>) [M+•-C<NUM>H<NUM>O<NUM>], <NUM> (<NUM>), <NUM> (<NUM>), <NUM> (<NUM>); FTIR (KBr): ṽmax = <NUM> (C-O), <NUM> (C-O), <NUM> (C-O), <NUM> (arom. C=C), <NUM> (aliph. C-H), <NUM> (aliph. C-H), <NUM> (aliph. C-H), <NUM> (aliph. C-H), <NUM> (aliph. C-H), <NUM> (polymeric O-H) and <NUM>-<NUM> (monomeric O-H).

According to the procedure reported by Meylemans et al. (<NUM>), <NUM> (<NUM> mmol) <NUM>-methoxy-<NUM>-methylphenol (Sigma-Aldrich, ≥<NUM>%) and <NUM> (<NUM> mmol) formaldehyde (Sigma-Aldrich, <NUM> wt%) were diluted with deionized water (<NUM>) in a <NUM> round-bottom flask. Concentrated HCl (<NUM>; Fisher Scientific, <NUM> wt%) was slowly added, and the reaction was heated to reflux under N<NUM> and magnetically stirred for <NUM> hours. A yellowish-green precipitate formed, the aqueous phase was decanted, and the organic precipitate washed with <NUM>% ethanol solution. Subsequently, the organic phase was dissolved in anhydrous diethyl ether (Sigma-Aldrich, ≥<NUM> %, <NUM>) and dried with anhydrous MgSO<NUM> (Sigma-Aldrich, ≥<NUM> %). An impure semi-crystalline yellowish-white powder was obtained by precipitation from ice-cooled n-heptane (<NUM>) in <NUM> wt% containing isomeric and oligomeric impurities (see <FIG>, <FIG>, <FIG> and <FIG>). The melting point of this precipitate lies at <NUM>-<NUM> (as determined by DSC), which agrees with the melting-range reported by Meylemans et al. (<NUM>), being <NUM>-<NUM>, but is significantly lower than the melting point (<NUM>-<NUM>; see REFERENCE EXAMPLE <NUM>) of analogous compounds resulting from our process.

According to the procedure reported by Meylemans et al. (<NUM>), <NUM> (<NUM> mmol) <NUM>-ethyl-<NUM>-methoxyphenol (Sigma-Aldrich, ≥<NUM>%) and <NUM> (<NUM> mmol) formaldehyde (Sigma-Aldrich, <NUM> wt%) were diluted with deionized water (<NUM>) in a <NUM> round-bottom flask. Concentrated HCl (<NUM>; Fisher Scientific, <NUM> wt%) was slowly added, and the reaction was heated to reflux under N<NUM> and magnetically stirred for <NUM> hours. A yellowish-orange oil resulted, the aqueous phase was decanted, and the organic oil washed with <NUM>% ethanol solution. Subsequently, the organic phase was dissolved in anhydrous diethyl ether (Sigma-Aldrich, ≥<NUM> %, <NUM>) and dried with anhydrous MgSO<NUM> (Sigma-Aldrich, ≥<NUM> %). An impure semi-crystalline yellowish-white powder was obtained by precipitation from ice-cooled n-heptane (<NUM>) in <NUM> wt% containing isomeric and oligomeric impurities (see <FIG>, <FIG>, <FIG> and <FIG>). The melting point (as determined by DSC) lies at <NUM>-<NUM>, which is significantly lower than the melting point (<NUM>-<NUM>; see REFERENCE EXAMPLE <NUM>) of analogous compounds resulting from our process.

According to the procedure reported by Meylemans et al. (<NUM>), <NUM> (<NUM> mmol) <NUM>-methoxy-<NUM>-propylphenol (Sigma-Aldrich, <NUM>+%) and <NUM> (<NUM> mmol) formaldehyde (Sigma-Aldrich, <NUM> wt%) were diluted with deionized water (<NUM>) in a <NUM> round-bottom flask. Concentrated HCl (<NUM>; Fisher Scientific, <NUM> wt%) was slowly added, and the reaction was heated to reflux under N<NUM> and magnetically stirred for <NUM> hours. A yellowish-red oil formed, the aqueous phase was decanted, and the organic oil washed with <NUM>% ethanol solution. Subsequently, the organic phase was dissolved in anhydrous diethyl ether (Sigma-Aldrich, ≥<NUM> %, <NUM>) and dried with anhydrous MgSO<NUM> (Sigma-Aldrich, ≥<NUM> %). While gradual evaporation of an diethyl ether/n-heptane solution yielded crystals (melting point <NUM>-<NUM>; see REFERENCE EXAMPLE <NUM>), precipitation from ice-cooled n-heptane (<NUM>-<NUM>) was not possible and yielded a suspension.

According to the procedure reported by Meylemans et al. (<NUM>), <NUM> (<NUM> mmol) <NUM>,<NUM>-dimethoxy-<NUM>-methylphenol (Alfa Aesar, <NUM> %) and <NUM> (<NUM> mmol) formaldehyde (Sigma-Aldrich, <NUM> wt%) were diluted with deionized water (<NUM>) in a <NUM> round-bottom flask. Concentrated HCl (<NUM>; Fisher Scientific, <NUM> wt%) was slowly added, and the reaction was heated to reflux under N<NUM> and magnetically stirred for <NUM> hours. A yellowish-white precipitate formed, the aqueous phase was decanted, and the organic oil washed with <NUM>% ethanol solution. Subsequently, the organic phase was dissolved in anhydrous diethyl ether (Sigma-Aldrich, ≥<NUM> %, <NUM>) and dried with anhydrous MgSO<NUM> (Sigma-Aldrich, ≥<NUM> %). An impure semi-crystalline off-white powder was obtained by precipitation from ice-cooled n-heptane (<NUM>) in <NUM> wt% containing oligomeric impurities (see <FIG>, <FIG> and <FIG>).

Claim 1:
A process for the production of aromatic dihydroxy compounds of ><NUM> wt% purity, with a general formula according to (I):
<CHM>
a. wherein X is an alkanediyl C1-C24 organic group;
b. wherein R<NUM> is independently selected from hydrogen, methyl or ethyl;
c. wherein R<NUM> is independently selected from methyl or ethyl;
d. wherein R<NUM> is independently selected from hydrogen, methoxy or ethoxy;
the process comprising:
(<NUM>) carrying out a condensation reaction of i) <NUM>-alkylphenol derivative and/or combinations thereof with ii) carbonylic compounds to produce a raw reaction product mixture,
(<NUM>) forming crystals of aromatic dihydroxy compounds by gradual evaporation directly of the solution of raw reaction product in a mixture of non-solvent alkane and solvent, whereby the gradual evaporation is at an evaporation rate that prevents precipitation, and
(<NUM>) separating said crystals.