Incorporation by Cross Reference

The present application claims priority from Australian provisional application no. 2013903917 filed on 1 1 October 2013, the entire contents of which are incorporated herein by cross-reference.

Technical Field

The present invention relates generally to the field of alkylation chemistry. More specifically, the present invention relates to the alkylation of phenolic compounds.

Background

Technological innovation driven towards the conversion of bio-resources, including biomass to liquid (BtL) technology, will be critical for delivering bio-based feedstocks for applications such as fuel blends. In addition to minimising dependence on oil, such biomass- deriyed "drop in" file! technology could lead to more expansive use of current petroleum reserves. Several technologies have been developed to convert biomass into a biofuei with a higher hearing value, such as gasification, pyrolysis and hydrothermal upgrading (HTU). In the HTU process, the biomass is treated for 5 to 20 minutes with water under suberitical conditions (300 to 350 °C, 10 to 18 MPa) to give a heavy organic liquid ('biocrude') with a heating value of between 30 and 35 M J kg.

The main components of biomass resources are typically macromolecules with high oxygen content, such as lignin, cellulose, hemiceilulose, and minerals. In various current biorefmer concepts, the cellulose and hemicellulose fractions are used to produce liquid transport fuel or products, while lignin is most often relegated to low-value uses including combustion. In currently operating bioreftnenes, lignin is either burned to produce process heat and recover pulping chemicals i n paper mills, or sold as a natural component of animal feeds in wet or dry corn mills.

Compounds obtained from the pyrolysis of biomass at 450 °C and compounds obtained from the HTU processing of lignin include low-moiecular weight aliphatics, lignin monomer molecules, oxidised lignin monomers, aromatic diacids, aromatic polyols, quinones, aromaties, O-heterocye!ic compounds, and phenolics. Compounds found in the aqueous fractions obtained from these methods specifically include low-molecular weight aliphatics (C i-C; aliphatics and formic or acetic acids, cyclohexanes and substituted cyclohexanes), phenol, guatacol, substituted guaiacols, syringo!, substituted syringols, substituted phenols, propylnhenol, eugenol, other alkylated methyl aryl ethers, oxidised lignin monomers (syrmgaldehyde. vanillin, vanillic acid), aromatic diacids, β-ketoadipic acid, aliphatic acids, aromatic polyols (eresol, catechol and derivatives, resorcinol, and resorcinol derivatives), quinones (hydroquinone, substituted hydroquinones) and aroroaties (benzene, toluene, xylene).

Once recovered from these processes, the phenolic compounds can be separated and purified for use as intermediates in the preparation of dyes, agrochernicais, fragrances and pesticides. However, as many phenolic compounds are corrosive and solid at room temperature, they must be converted to less corrosive derivatives with lower melting points prior to use as fuel additives. Technological innovation driven towards the conversion of lignin -derived phenolic compounds, in particular to provide alternatives to classical hydro deoxygenation processes, will be critical for delivering bio-based feedstock for fuel blends. One such alternative is O-alkylation processes, which convert the lignin-derived phenolic compounds to alky I -aryl ethers.

Current processes for the selective alkylation of phenolic compounds such as those obtained from the HTU of lignin suffer from a number of drawbacks, in particular, methylated phenolic compounds, including phenols and benzenediols, are conventionally synthesized by ()- methylation of the corresponding phenols with mutagenic methyl halides, dimethyl sulfate, or methanol under harsh conditions. In contrast to rnethy!ation of phenols, which can proceed selectively under mild conditions with dimethyl carbonate (D C), the methyl ati on of benzenediols requires high temperatures and pressures and occurs with poor selectivities; typical product mixtures contain a variety of non-metiiylated, partially methylated, and fully methylated compounds, for example, guaiacol, catechol carbonate, veratrole, etc. This poor selectivity renders the reaction protocols that are successful for methyl ating phenol (and substituted phenols) less useful for producing fe-methylated products for their potential use in fuel blends. Current methods for the methyl ation of benzenediols require ionic liquids,

K2CO3-BU4NB1-, DBU, or explosive reagents such as A ^r ,/V-dimethylformamide dimethyl acetal DMF-DMA, ail of which are expensive, afford poor conversions and low selectivities, and are difficult to carry out on an industrial scale. Further,, current methods for conducting

methylation/alkylation reactions involving phenolic compounds require a feedstock substantially free of water, as water can decompose the alkylating agent or slow down the alkylation reaction by competing with the substrate for catalytic sites. As phenolic compounds obtained from bioniass pyrolysis and HTU processing must be isolated and recovered from an aqueous fraction, trace amounts of water may be present in the alkylatioii reaction mixture.

Therefore, there is a need for a general, mild method for the complete and selective aiky!ation of phenolic compounds, in particular benzenediols. to expand the utility of phenolic fragments obtained from various sources including the thermal processing of lignin. There is also a need for a method for alkylatioii of phenolic compounds that is tolerant to the presence of water in the feedstock, whilst still retaining high conversions and selecti ities to the fully alkylated product(s).

Summary of the Invention

In a first aspect of the present invention there is provided a process for O-alkylation of a phenolic compound comprising at least two hydroxy! groups ^' bonded to an aromatic

hydrocarbon, the process comprising reacting the phenolic compound with an alkylating agent in the presence of a base, at a suitable reaction temperature and for a suitable time period, thereby alk lating the at least two hydroxy 1 groups.

The following options may be used in conjunction with the first aspect either individually or in any suitable combination.

The phenolic compound may comprise two, three, four, five or six hydroxyl groups bonded to the aromatic hydrocarbon. The phenolic compound may further comprise one or more substituents selected from the group consisting of linear or branched€ alkyl, Ci.g eycloalkyl, C alkoxy, Ci-g carboxy, Ci-s alkyenyl, Ci-s ajkynyl, Cj-s hydroxyalkyi, Ci-s alkoxyalkyl, C ^' i.g cyanoalkyl, Ci^ alkoxycarbonyl, O-s alkanoyi, and Ci-s oxoalkyl.

The aromatic hydrocarbon may be a monocyclic aromatic hydrocarbon or may be a polycyclic aromatic hydrocarbon. When the aromatic hydrocarbon is monocyclic, the monocyclic aromatic hydrocarbon may be benzene. When the aromatic hydrocarbon is polycyclic, the polycyclic aromatic hydrocarbon may be a fused or non-fused polycyclic aromatic hydrocarbon selected from the group consisting of naphthalene, phenanthrene, anthracene, pyrene, tetracene, biphenyl, diphenylmethane, diphenylethane, diphenylethene, dtphenylpropane and diphenylpropene. Therefore, the phenolic compound may be a hydroxy- substituted benzoic acid, a hydroxy substituted benzaldehyde, or a hydroxy substituted acetophenone. The phenolic compound ma comprise two bydroxyi groups bonded to the aromatic hydiocarbon and may be either a benzenediol or a substituted benzenediol. The benzene may be substituted according to formula I:

wherei R ^s to R. ^"' are independently selected from the group consisting of— H, Ci. _& alkyl, Ci-8. alkoxy and -OH, and wherein at least one of R ¹ to R ^"' is -OH. The phenolic compound may be selected from the group consisting of 1 ,2 -benzenediol, 1 ,3-henzenediol, 1,4- benzenediol, 4-methyi-l,2-baizenediol, 2-methyL- 1 ,4-benzenediol, 2,3-dimethyl-l ,4- benzenediol and 4-ethyl-l ,2-benzenediol. In a process for O-alkylation of a phenolic compound comprising at least two hydroxyl groups bonded to an aromatic hydrocarbon, at least two of said hydroxy l groups may be alkylated upon completion of the process.

The phenolic compound may comprise at least three hydroxy! groups bonded to an aromatic hydrocarbon. In a process for O-alkylation of a phenolic compound comprising at least three hydroxy ! groups bonded to an aromatic hydrocarbon, at least three of said hydroxyl groups may be alkylated upon completion .of the process. In a process for O-alkylation of a phenolic compound comprising four or more hydroxyl groups bonded to an aromatic

hydrocarbon, all of said hydroxyl groups may be alkylated upon completion of the process.

The phenolic compound ma be obtained from an aqueou fraction of pyro lytic treatment or hydrothennal. upgrading of iignin.

The alkylating agent may be an organic carbonate, for example, it may be a dialkyl carbonate. The dialkyl carbonate may be selected from the group consisting of dimethyl carbonate, diethyl, carbonate, dipropyl carbonate, ditsopropyl carbonate, dicyelohexyl carbonate, eth.ylmeth.yl carbonate, propylmethyl carbonate, and cyclohexylmethyl carbonate. The alkylating agent may be dimethyl carbonate. The molar ratio of the hydroxy! groups to the alkylating agent may be between about 1 :40 and about 1 :20.

The base may be an inorganic base. The inorganic base may be selected from the group consisting of potassium hydroxide, lithium hydroxide, sodium hydroxide, aluminium hydroxide, potassium carbonate, caesium carbonate, calcium carbonate, sodium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, manganese dioxide, and compounds of the nature MOR, where M is Li, Na, K or Tl and R is methyl, ethyl, propyl, isopropyl. tert-butyl, or phenyl The inorganic base may be caesium carbonate. The base may be substantially soluble in a reactio mixture comprising the phenolic compound, the alkylating agent and the base that is used for the reacting. The base may be an organic base. The organic base may be selected from the group consisting of pyridine, l ,4-diazabicyclo[2.2,2]octane, l,8-diazabicycloundec-7- ene, and triethylam e. The molar ratio of the hydroxy! groups to the base may be between about 5: 1 and 1 :5. The base may be catalytic.

In a process for O-alkylation of a phenolic compound comprising at least two hydroxyl groups bonded to an aromatic hydrocarbon, the process comprising reacting die phenolic compound with an alkylating agent in the presence of a base, at a suitable reaction temperature and for a suitable time period, thereby O-alkylating the at least two hydroxyl groups, the reacting may further comprise reacting the phenolic compound with the alkylating agent in the presence of the base and in the presence of water. The molar ratio of the water to the phenolic compounds may be about 5: 1. The reacting may further comprise reacting the phenolic

compound with the alkylating agent in the presence of the base in a solvent. The sol vent may be a polar solvent. The polar solvent may be selected from the group consisting of water, acetoiiitrile, xylene, dimethylsuifoxide, methylene glycol dimethyl ether (triglyme),

dimethylfortTiarnide, N-.rn.ethyl-2-pyr.rolidone, methanol, ethanol, and /erZ-butanoi, or any combination thereof. The solvent may be acetonitrile.

The reacting may be conducted at temperature of between about 170 °C and about 200 °C. t may be conducted at a pressure of between about 1 bar and about 30 bar. The reacting may proceed for between about 20 mm and about 240 mm. It may be conducted in the presence of microwave irradiation. The reacting may be conducted in a batch .microwave or in. a flow microwave. The microwave radiation may be focussed microwave radiation, in which case the microwave radiation may be supplied by a focussed batch microwave, or a focussed flow microwave. The process may result in a yield of a fully alkylated phenolic product of between about 80% and about 100%.

The process may .further comprise separating the base from the alky lating agent, and/or the phenolic compound, and/or an O-alkylated phenolic compound, subsequent to the reacting. Subsequent to the reacting, the. process may further comprise contacting the base with an additional phenolic compound and an additional alkylating agent, wherein the additional phenolic compound may comprise a plurality of hydroxyl groups bonded to an aromatic hydrocarbon; and, reacting the additional phenolic compound, the additional alkylating agent, and the base at a further suitable reaction temperature and for a further suitable time period for O-aikylation of the pluralit of hydroxy! groups. The process may compri se conducting between 1 and J 00 cycles of the process subsequent to the reacting. Each cycle may comprise contacting the base with an additional phenolic compound and an additional alkylating agent, wherein the additional phenolic compound comprises a plurality of hydroxyl groups bonded to an aromatic hydrocarbon; and, reacting the additional phenolic compound, the additional alkylating agent, and the base at a further suitable reaction temperature and for a further suitable time peri od for O-aikylation of the plurali ty of hydroxy! groups.

The additional phenolic compound may be selected from the group consisting of 1 ,2- benzenedioi, 1 ,3-benzetiediol, 1 ,4-bertzenediol, 4-tneth l- 1,2-benzenedio!, 2 -methyl- 1,4- benzenediol, 2,3-dimeihyI-1.4-benzenediol and 4-ethyl-l,2-beitzeftediol. The additional alkylating agent may be selected from the group consisting of dimethyl carbonate, diethyl carbonate, dipropyl carbonate, diisopropyl carbonate, dic clohexyl carbonate, ethylmethyl carbonate, propylmethyl carbonate, and cyclohexylmethyi carbonate. The further suitable reaction temperature may be between about 170 °C and about 200 °C. The further suitable reaction time may be between about 20 mm and about 240 miti. The process may further comprise reacting the additional phenolic compound, the additional alkylating agent, and said base in the presence of additional water and'Or an additional organic or inorganic solvent. The phenolic compound and the additional phenolic compound may be identical The alkylating agent and the additional alkylating agent may be identical. Each suitable reaction temperature and/or each suitable reaction time may be identical.

In one embodiment there is provided a process for O-aikylation of a phenolic compound comprising at least two hydroxyl groups bonded to an aromatic hydrocarbon, wherein the aromatic hydrocarbon is benzene and wherein the phenolic compound is a benzenediol or substituted benzenediol, wherein the substituents are selected from the group consisting of linear or branched Cj.g alkyl, aikoxy, Ci_s carboxy, Cj-g alkyenyl, Cw aikyny!, Cj. 8 hydroxyalky], Cj.s alkoxyalkyl, Ci-s cyanoalkyl, Ci-s alkoxycarbonyl, Ci-g alkanoyl, and Ci_¾ oxoalkyi the process comprising reacting the phenolic compound with an alkylating agent, wherein the alkylating agent is a diaikyl carbonate, in the presence of a base, wherein the base is potassium carbonate, caesium carbonate, calcium carbonate, or sodium carbonate, at a reactio temperature of between about 170 °C and about 200 °C and for a time period of between about 20 mm and about 240 min, thereby alkylating a plurality of said hydroxyl groups, wherein the molar ratio of the hydroxyl groups to the alkylating agent is between about 1:40 and about 1 :20, the molar ratio of the hydroxyl groups to the base is between about 5: 1 and 1 :5, wherein the reacting is conducted in the presence of microwave irradiation and further comprises reacting the phenolic compound with the alkylating agent in the presence of the base in a polar solvent.

In another embodiment there is provided a process for O-alkylation of a phenolic compound comprising at least two hydroxyl groups bonded to an aromatic hydrocarbon, wherem the aromatic hydrocarbon is benzene and wherein the phenolic compound is 1,2- benzenediol, 1,3-benzenedioL or 1,4-benzenediol, 4-rnetb.yl- 1.2-benzenedtol, 2-methyI-l ,4- benzenediol, 2,3-dimethyi-l ,4-benzenediol or 4-ethyi- 1 ,2-benzenediol, the process comprising reacting the phenolic compound with an alkylating agent, wherein the alkylating agent is dimethyl carbonate, in the presence of a base, wherein the base is caesium carbonate, at a reaction temperature of between about 170 °C and about 200 °C and for a time period of between about 20 min and about 180 min and a pressure of between about 1 bar and 30 bar , thereby alkylating at least two of said hydroxyl groups, wherein the molar ratio of the hydroxyl groups to the alkylating agent is between about 1 :40 and about 1 :20, the molar ratio of the hydroxyl groups to the base is between about 5:1 and 1 :5, wherein the reacting is conducted in the presence of microwave irradiation further comprises reacting the phenolic compound with the alkylating agent in the presence of the base i aeetonitrile solvent, wherein the process results in a yield of a fully alkylated phenolic product of betwee about 80% and about 1 0%.

I another embodiment there is provided a process for O-alkylation of a phenolic compound comprising at least two hydroxyl groups bonded to an aromatic hydrocarbon, wherein the aromatic hydrocarbon is a polycyclic aromatic hydrocarbon and wherein the phenolic compound is dfliydroxy biphenyl or napthalenediol or a substituted dihydroxy bip eny! or napthalenediol, wherein the substituents are selected from the group consisting of linear or branched C alkyl, Ci-s cycloalkyl, Ci-g aikoxy, Q-g carboxy, Ci-g alkyenyl, Ci-g alkynyl, Ci-g hydroxyalkyl. Cm alkoxyalkyl. Cm cyanoalkyl, C _5- s alkox.ycarbon.yl. Cm alkanoyl, and . Cm oxoalkyl, the process comprising reacting the phenolic compound with an alkylating agent, wherein the alkylating agent is a dialkyl carbonate, in the presence of a base, wherein the base is caesium carbonate, at a reaction temperature of between about 170 °C and about 200 °C and for a time period of between about 20 min and about 240 min, thereby alkylating at least two of said hydroxy! groups, wherein the molar rati o of the hydroxyl groups to the alkylatin agent is between about 1 :40 and about 1 :20, the molar ratio of the hydroxyl groups to the base is between about 5:1 and 1:5, wherein the reacting is conducted in the presence of microwave irradiation and further comprises reacting the phenolic compound with the alkylating agent in the presence of the base in a polar solvent.

In another embodiment there is provided a process for O-alkylation of a phenolic compound comprising at least two hydroxyl groups bonded to an aromatic hydrocarbon, wherein the aromatic hydrocarbon is a polycyclic aromatic hydrocarbon and wherein the phenolic compound is dihydrox biphenyl or napthalenediol or a substituted dihydroxy biphenyl or napthalenediol, wherein the substituents are selected from the group consisting of linear or branched C1 alkyl, Ci-g cycloalkyl, Ci-8 alkoxy, Cm carboxy, O-g alkyenyl, Ci-g aikynyl, Ci-s hydroxyalkyl, m alkoxyalkyl, m cyanoalkyl, Ci-g alkoxyearbony!, Ci-& alkanoyl, and Ci.s oxoalkyl, the process comprising reacting the phenolic compound with an alkylating agent, wherein the alkylating agent is dimethyl carbonate, in the presence of a base, wherein the base is caesium carbonate, at a reaction temperature of between about 170 °C and about 200 °C and for a time period of between about 20 min and about 120 min and a pressure of between about 1 bar and 30 bar, thereby alkylating at least two of said hydroxyl groups, wherein the molar ratio of the hydroxy! groups to the alkylating agent is between about 1:40 and about 1 :2Q, the molar ratio of the hydroxyl gro ups to the base is between about 5:1 and 1:5, wherein the reacting is conducted in the presence of microwave irradiation further comprises reacting the phenolic compound with the alkylating agent in the presence of the base in acetonitrile solvent, wherein the process results in a yield of a fully alkylated phenolic product of between about 80% and about 100%.

In a further embodiment there is provided a process for 0-aIkylation of a phenolic compound comprising at least two hydroxyl groups bonded to an aromatic hydrocarbon, the process comprising reacting the phenolic compound with an alkylating agent, wherein the alkylating agent is dimethyl carbonate, in the presence of a base, wherein the base is caesium carbonate, at a reaction temperature of between about 170 °C and about 200 °C and for a time period of between about 20 mm and about 240 min, thereby alkylating at. least two of said hydi oxyl groups, wherein the molar ratio of the hydroxyl groups to the alkylating agent is between about i :40 and about 1 :20, the molar ratio of the hydroxyl groups to the base is between about 5:1 and 1:5, wherein the reacting is conducted in the presence of microwave irradiation and further comprises reacting the phenolic compound with the alkylating agent in the presence of the base in acetomtrile solvent, wherein the process results in a yield of a fully alkylated phenolic product of between about 80% and about 100%.

In yet a further embodiment there is provided a process for O-alkylation of a phenolic compound comprising at least two hydroxyl groups bonded to an aromatic hydrocarbon, wherein the phenolic compound is 1,2-benzenediol, 1,3-benzenediol, 1 ,4-benzenediol, 4-methyi- 1,2-henzenedioi, 2-methyl-l ,4-benzenediol, 2,3-dimethyi-l. _s 4-benzenediol, 4-ethyl-l,2- benzenediol, 2-2 ⁱ -dihydroxybipheiiyL or naphthalene-2,3-diol, the process comprising reacting the phenolic compound with an alkylating agent, wherein the alkylating agent is a dialkyl carbonate, in the presence of a base, wherein the base is potassium hydroxide, at a reaction temperature of between about 170 °C and about 200 °C and for a time period of between about 20 min and about 240 min, thereby alkylating at least two of said hydroxyl groups, wherein the molar ratio of the hydroxyl groups to the alky lating agent is between about 1 :40 and about 1 :20 ₅ the molar ratio of the hydroxyl groups to the base is between about 5: 1 and 1:5, wherein the reacting may further comprise reacting the phenolic compound with the alkylating agent in the presence of the base in a polar solvent and in the presence of water, wherei n the molar ratio of the water to the phenolic compounds is about 5:1.

In another embodiment there is provided a process for O-alkylation of a phenolic compound comprising at least two hydroxyl groups bonded to an aromatic hydrocarbon, the process comprising reacting the phenolic compound with an alkylating agent, wherein the alkylating agent is a di alkyl carbonate, in the presence of a base, wherein the base is potassium carbonate, caesium carbonate, calcium carbonate, or sodium carbonate, at a reaction temperature of between about 170 °C and about 200 °C and for a time period of between about 20 mi and about 240 min, thereby alkylating a plurality of said hydi oxyl groups, wherein the molar ratio of the hydroxyl groups to the alkylating agent is between about 1 :40 and about 1 :20, the molar ratio of the hydroxy! groups to the base is between about 5: 1 and 1 :5, wherein the reacting is conducted in the presence of microwave irradiation and further comprises reacting the phenolic compound with the alkylating agent in th presence of the base i n a pol ar sol v ent, and wherein the process still further comprises separating the base from the alkylating agent, and/or the phenolic compound,, and or an -alkylated phenolic compound, subsequent to the reacting.

In a further embodiment there is provided a process for O-alkylation of a phenolic compound comprising at least two hydroxy! groups bonded to an aromatic hydrocarbon _. , the process comprising reacting the phenolic compound wit an alkylating agent in the presence of a base, at a suitable reaction temperature and for a suitable time period, thereby alkylating a plurality of said hydroxy! groups, wherein the reacting is conducted in the presence of microwave irradiation and further comprises reacting the phenolic compound with the alkylating agent in the presence of the base in a polar solvent, and wherein the process still further comprises separating the base from the alkylating agent, and'or the phenolic compound, and/or an O-alkylated phenolic compound subsequent to the reacting, and then contacting the base with an additional phenolic compound and an additional alkylating agent, wherein the additional phenolic compound may comprise a plurality of hydroxy! groups bonded to an aromatic hydrocarbon, and reacting the additional phenolic compound, the additional alkylating agent, and the base at a further suitable reaction temperature and for a further suitable time period for O-alkylation of the plurality of hydroxy! groups such that the process comprises between .1 and 100 cycles of the process subsequent to the reacting.

In a second aspect of the present invention there is provided an O-alkylated phenolic compound produced in accordance with the process of the first aspect.

Brief Description of the Drawings

Preferred embodiments of the present invention will now be described, by way of exampl e only, with reference to the accompanying figures wherein;

Figure 1 shows a process design fo a flow reactor, with exemplary/non-limiting reaction conditions for the dialkylation of benzenediols.

Figure 2 shows the concentration of the reaction mixture as reported by control software for the flow reactor relative to steady state at the reactor outlet.

Definitions

As used in this application, the singular form "a", "an" and "the" include plural references unless the context clearly dictates otherwise. For example, the phrase "a benzenedioi" also includes a plurality of benzenedioi compounds. Π

As used h erein, the term "comprising" means 'Inc luding-" Variations of the word "comprising", such as "comprise" and "comprises," have correspondingly varied meanings. Thus, fo example, a phenolic compound "comprising" two hydroxy! groups may have, for example, two hydroxy! groups only attached to an aromatic hydrocarbon, or may have more than two hydroxyl groups or two hydroxy! groups and at least one other substituent group attached to an aromatic hydrocarbon.

As used herein, "aik.ylati.on" exclusively refers to O-alkylation.

As used herein, "phenolic compounds' ^" refer to compounds comprising at least, one hydroxyl group bonded directly to an aromatic hydrocarbon group, including, but not limited to, compounds comprising two, three, four, five or six hydroxyl groups bonded directly to an aromatic hydrocarbon group.

As used herein, the term "aromatic hydrocarbon group" refers to a monocyclic or fused or non-fused potycyclic aromatic hydrocarbon group.

As used herein, the terms "phenol" and "phenols" refer to the compound

hydroxybenzene (CeHsOH) containing one- hydroxyl group bonded directly to an aromatic hydrocarbon group, or to one or more substituted phenol compounds containing no more than one hydroxyl group bonded directly to an aromatic hydrocarbon group.

As used herein, the terms "benzenediol" refers to a compound containing two hydroxyl groups bonded directly to a benzene group. Such compounds may also be referred to as "dihydroxybenzene compounds". Non-limiting examples of benzenediols include catechol (1 ,2- di hydroxybenzene or 1 ,2 -benzenediol), resorcinol (1,3-d.ihydroxybenzene or 1.3-benzenediol). hydroquinone (1 ,4-dihydroxybenzene or 1 ,4-benzettedioi). "Benzenediol" also encompasses substituted benzenediols., for example methyl and ethyl substituted benzenediols including 4- methylcatecbol, methylhydroquinone, 4-ethyicatechol, 2,3-dimethylhydroquinone, and the like. The term "dihydroxybenzene compounds" also encompasses substituted benzenediols where the substituents have a higher order of precedence in naming than hydroxyl substituenis, for example, substituents including carboxylic acid(s) or a!dehyde(s). Such compounds are also understood to be encompassed by the term "benzenedio!' ⁵ , e.g. , 2,5-dihydroxybenzoic acid.

As used herein, "phenolic diether" and "alkylated phenolic diether" refer to a phenolic compound containing two hydroxyl groups- wherein the two hydroxyl groups have been O- alkylated to form an aryl-alkyl diether. As used herein, the terra " v-alkylated product" is also taken to mean a phenolic compound, containing two hydroxy! groups wherein the two hydroxy! groups have been 0-aikylated to form an aryl-alk l diether.

As used herein, the abbreviation "DMC" is taken to mean, dimethylcarbonate; "DBA" is taken to mean 1 ,4-diazabicydo[2.2.2]octane, "DBU" is taken to mean

1 ,8-diazabicyclo[5,4.0]undec-7-ene, and 'FBAI is taken to mean er 'butyiammonium iodide.

As used herein the term "plurality" means more than one. In certain specific aspects or embodiments, a plurality may mean 2, 3, 4, 5, 6, 7, 8, 9, 10, I I, 12. 13, 14, 15, 16, 17, 18, 19, 20, or more, and any integer derivable therein, and any range derivable therein.

It will be understood that use the term "about" herein in reference to a recited numerical value includes the recited numerical value and numerical values within plus or minus ten percent of the recited val ue , unless the context, indicates otherwise.

It will be understood that use of the term "between" herein when referring to a range of numerical values encompasses the numerical values at each endpomt of the range. For example, a temperature of between 95 °C and 125 °C is inclusive of a. temperature of 95 °C and a temperature of 125 °C.

Any description of prior art documents herein, or statements herein derived from or based on those dociiments, is not an admission that the documents or derived statements are part of the common general knowledge of the relevant art.

For the purposes of description all documents referred to herein are hereby incorporated by reference in their entirety unless otherwise stated.

Description of Embodiments

The present in vention relates to a process for the O-alkylation of phenolic compounds which comprises reacting the phenolic compounds with an alkylating agent in the presence of a base. As noted above, the selecti ve alkylation of phenolic compounds requires further improvement as current methods emplo toxic and/or mutagenic reagents, high temperatures and pressures to achieve sufficient yields, and often afford poor conversions, low selectivities and low yields. In particular, current methods to achieve the O-alkylation of phenolic compounds comprising at least two hydroxy!, groups do not effect complete alkylation, and therefore the reaction products may not be suitable for use as fuel additives. Phenolic Compounds

The process described herein is particularly suitable for the O-a!kyiation of phenolic compounds, and in particular, phenolic compounds comprising at least two Iiydroxyl groups.

Phenolic compounds treated in accordance with the present invention may comprise at least two Iiydroxyl groups bonded to an aromatic hydrocarbon. The aromatic hydrocarbon may be a monocyclic or polycyclic aromatic hydrocarbon. The monocyclic aromatic hydrocarbon may be benzene. The polycyclic hydrocarbon group may compose more than two fused aromatic rings, non-limiting examples of which include two, three, four, five and six fused ring compounds and their isomers, e.g., naphthalene, phenanthrene, anthracene, pyrene and tetraeene. The aromatic hydrocarbons may be non-fused polycyclic aromatic hydrocarbons, e.g., may be biphenyl, or may be diphenylmethane, diphenylethane, diphetrylethene,

diphenylpropane, diphenylpropeoe, or isomers thereof.

Phenolic compounds treated in accordance with the present invention may comprise one or more aromatic hydrocarbons as described above to which two hydroxy! groups, or more than two hydroxy! groups, may be directly bonded. Accordingly, when, the aromatic hydrocarbon group is benzene, the phenolic compounds ma be benzenediols, non-limiting examples of which include 1 ,2-benzenediol (catechol), 1 ,3-benzenediol. (resorcmo!) and 1 ,4-benzenediol (bydroqurnone) as shown in Structures 1A, S B and 1 C, respectively, below.

Structure 1A Structure IB Structure lC

The benzenediols may be substituted, e.g., they may be alkyi-substituted benzenediols or alkoxy-substituted benzenediols. Non-limiting examples of alkyl substituents include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, or an other Ci. ₈ alkyl group. The aforementioned alkyl Substituents may be linear or branched alkyl groups. They may be cydoalkyl groups, e.g., Cj^ cycloalkyl groups. Non-limiting examples of alkoxy substituents include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, or any other Ci-s alkoxy group. The alkoxy

substituents may be linear or branched alkoxy groups. The benzenediols may additionally or alternati vely comprise other stibstituents, e.g., one or more carboxyl groups, formyl groups, aryloxyl groups, alkenyl groups, alkynyl groups, alkyl or aryl carbonyloxy groups including alkyl or aryl acetoxy groups, alkoxyalkyi groups, hydroxyalkyl groups or cyanoalkyl groups. The benzenediols may be hydroxy-substituted benzoic acid, or hydroxy substituted

benzaldehyde, or hydroxy substituted acetophenone.

The benzenediols may be non-substituted, mono-substituted, di-substituted, tri- substituted or tetra-substituted, and the stibstituents may be any one or more of those

substituents as described above, e.g., alkyl, alkoxy, carboxy, aryloxy, alkenyl, alkynyl,

alkoxyalkyi, hydroxyalkyl, cyanoalky] or a mixture of any two or more of these groups. Non- limiting examples of substituted benzenediols include 4-methyl-l ,2-benzenediol, 2-meth.yl- 1 ,4- benzenediol, 2,3-dimethyl- 1 ,4-benzenediol, 4-ethyl-i,2-benzenediol as shown in Structures 2A, 2B, 2C and 2D, respectively, below, and 2,5-dihydroxybeozoic acid, 2,3-dihydroxybenzoic acid, 3,4-dibydiOxybenzoic acid, 2,5-dihydroxybenzaldehyde, 2,3-dihydroxybenzaldehyde, 3,4- dihydroxybenza!dehyde, 3 ,4-dihydroxyacetophenone, 2,4-d ydroxyacetophenone, 3,4- diliydroxybeixzyl alcohol, 3,5-dihydxoxybenzyi alcohol, 3,4-dihydroxybenzonitrile, 2,3- dihydroxybenzonitrile, and 3,4-dihydroxyallyIbenzene.

The phenolic compounds treated in accordance with the present invention may comprise one or more aromatic hydrocarbons as described above to which three hydroxy! groups or more than three hydroxy! groups may be directly bonded. The phenolic compounds may be

henzenetriols, non-limiting examples of which include 1 ,2,3-benzenetriol, 1,3,5-benzenetr and 1 ,2,,4-benzenerriol. The henzenetriols may be substituted as described above for

benzenediols, eg, , the benzenetriols may be non-substituted, mono-substituted, di-substituted or tri-substituted and the benzenetriols may be alkyl, alkoxy, carboxy, aryloxy, alkenyl, alkynyl, alkoxyalkyl, hydroxyalkyl, or cyanoalkyl substituted, or substituted by a mixture of any two or more of these groups.

The phenolic compounds treated in accordance with the present invention may comprise on or more aromatic hydrocarbons as described above to which four, five or si hydroxy ^} groups or more than four, five or six hydroxy! groups may be directly bonded. Accordingly, the phenolic compounds may be benzenetetrols, non-limiting examples of which include 1 ,2,3,4- benzenetetrol, 1 ,2,3,5-beiizenetetrol and 1 ,2,4,5-benzenetetroL The benzenetetrols may be substituted as described above for benzenediols, e.g., the benzenetetrols may be now -substituted, mono-substituted, or di -substituted and. the benzenetetrols may be alkyl, alkoxy, earboxy, aryioxy, alkenyl, alkyrryl, alkoxyalkyl, hydroxyalkyl, or cyanoalkyl substituted, or substituted by a mixture of any two or more of these groups. The phenolic compounds may also be pentahydroxybenzenes, a non-limiting example of which includes 1,2,3,4,5- pentahydroxybenzene. The pentahydroxybenzenes may be substituted as described above for benzenediols, e.g., the pentahydroxybenzenes may be mono-substituted, and the substkiient may be an alkyl, alkoxy, carboxy, aryioxy, alkenyl, alkynyl, alkpxyalkyl, hydroxyalkyl, or cyanoalkyl group. The phenolic compound may also be hexahydroxybenzene.

In some embodiments, phenolic compounds may be utilised wherein the aromatic hydrocarbon is benzene, and the benzene is substituted according to formula 1:

wherein ¹ to R ⁵ are independently selected from the group consisting of-H, linear or branched Ci-8 alkyl or cycloalkyl, C j. alkoxy and -OH, and wherein at least one of R ¹ to R ⁵ is -OH.

The phenolic compounds may comprise aromatic hydrocarbons other than benzene to which the at least two hydroxy! groups may be directly bonded, non-limiting examples of which include poiyaromatic hydrocarbons comprising two, three, four, five or six fused rings and their isomers, e.g., naphthalene, phenanthxene, anthracene, pyrene and tetracene. Where the polyaromatic hydrocarbons comprise two or more fused rings, the phenolic compounds may comprise more than one, two, three, four, five, six, seven, eight, nine, or more than ten hydroxy! groups, directly bonded to the aforementioned polyaromatic hydrocarbon, e.g., two, three, four, five, six, seven, eight, nine, or ten hydroxy! groups directly or indirectly bonded to the aforementioned polyaromatic hydrocarbon. Non-limiting examples of hydroxy-substituted polyaromatic hydrocarbons include 1,5-naphthalenediol, 2,3-naphthalenediol, 2,7- naphthalenedioi, 9,10-anthracenediol and 3,4-dihyaroxyphenanthrene. The phenolic compounds may comprise aromatic hydrocarbons other than benzene to which the at least two hydroxy! groups may be directly bonded, non-limiting examples of which include non-fused polycyclic aromatic hydrocarbons, anon-limiting example of which is biphenyl. Where the non- fused polycyclic aromatic hydrocarbons comprise two or more non-fused aromatic rings, the phenolic compounds ma comprise more than one, two, three, four, five, six, seven, eight, nine, or more than ten hydroxy! groups, directly or indirectly bonded to the aforementioned non-fused polycyclic aromatic hydrocarbon, e.g., two, three, four, five., six, seven, eight, nine, or ten hydroxyl groups directly bonded to the aforementioned non-fused polycyclic aromatic hydrocarbon. Non-limiting examples of hydroxy-substituted non-fused polycyclic aromatic hydrocarbons include 2,2 -dihydroxybiphenyi, 4,4'-diliydroxybiphenyl, .2,3'-dihydroxybiphenyl, 2,4'-dihydroxybiphe.nyl. and 3,3'-methyienebis(benzene- l ,2 _r dioi).

The process may encompass the O-alkylation of a mixture of phenolic compounds as described above, or a mixture comprising one or more phenolic compounds as described above, wherein the one o more phenolic compounds are reacted with an alkylating agent in the presence of a base. The mixture of phenolic compounds may comprise one or more benzenediol compounds, substituted benzenediol compounds, benzenetriol compound and/or substituted benzenetriol. compounds as described above. The mixture of phenolic compounds may comprise any two or more, any three or more, any four or more, any five or more, any six or more, or any seven of the following compounds: 1,2 -benzenediol, 1 ,4-henzenedioL. 4-methyl- l ,2-benzenediol, 2-methyl- 1,4-benzenediol, 1 ,3-benzenediol, 2,3-dime yl- 1 ,4-benzenediol, and 4-ethyl- 1 ,2-benzenediol. The mixture may comprise these phenolic compounds in eqoimolar or approximately equimolar amounts. N on-limiting examples of mixtures may include those comprising 1 :1, 1 :2, 2:1 , 1 :3, 3:1., 1:4, 4; I, 1:5 or 5: 1 ratios by mole or by mass of 1 ,2- benzenediol and 1,4-benzenediol; 1 ,2-benzenediol and 4-methyl.-l ,2-benzenediol; 1,2- benzenediol and 2-methyl-l ,4-benzenediol; 1 ,2-benzenediol. and 1 ,3-benzenediol: 1 ,2- benzenedioi and 2,3-diraethyl-l ,4-benzenediol; 1 ,2-benzenediol and 4-ethyl- 1 ,2-benzenediol; 1,4-benzenediol and 4-m.ethyl-l ,2-benzenediol; 1,4-benzenediol and 2-methyl- 1,4-benzenedioi; 1,4-benzenediol and 1 ,3 -benzenedioi; J ₅ 4-benze»ediol and 2,3-dtniethyl- 1 ,4-benzenediol; 1,4- benzenediol and 4-ethyl- .1 ,2-benzeaediol; 4-methyl-l ,2-benzenediol and 2-methyl- 1 ,4- benzenediol: 4-methyl- 1 ,2-benzenediol and 1.3-benzenediol; 4-methyl- 1 ,2-benzenediol and 2,3- dimetbyl- 1 ,4-benzenediol ; 4-methy1-l ,2-benzenediol and 4-ethyl- 1 ,2-benzenediol; 2-mediyl- 1 ,4-henzenedi f and 1,3 -benzenedioi; 2-methyl- 1,4-benzenediol and 2,3-dimethyl- 1 ,4- benzenediol; 2-methyl- 1 ,4-benzenediol and 4-ethyl- 1,2-benzenediol; 1 ,3-benzenediol and 2,3- diroethyi- 1 ,4-benzenediol; 1,3-benzenediol and 4-ethyi-l,2-benzenediol; and 2,3-dimethyl- 1,4- benzenediol and 4-ethyl-l,2-benzenediol. Further non-limiting examples of mixtures may include those comprising 1:1 : 1, 1 :2: 1, 2:1: 1, 1:1:2, 1:3: 1., 3:1:1, 1:1:3, 1:2:3, 1 :3:2, 2: 1 :3, 2:3: 1 , 3 : 1 :2 or 3:2: 1 ratios by mole or by mass of 1,2-benzenediol, 1,4-benzenediol and 4-methyl- 1,2- benzenediol; 1,2-benzenediol, 1,4-benzenediol and 2-methyl- 1,4-benzenediol; 1 ,2-benzenediol, 1 ,2-benzenediol, and 1,4-benzenediol; etc.

Phenolic Compound Feedstock

Phenolic compounds or mixtures thereof treated i accordance with the process of the present invention may be derived from any suitable source. For example, the phenolic

compounds may be provided in an aqueous fraction obtained from the pyrolytic treatment and/or hydrothermal upgrading of lignin-containing biomass. Any appropriate lignin-containing biomass source may be used as feedstock for the pyrolytic treatment and/or hydrothermal upgrading process, non-limiting examples of which may include woody plant matter or components thereof, fibrous plant matter or components thereof, agricultural crops or

agricultural crop residues, including fruits, flowers, grains, grasses, herbaceous crops, wheat straw, switchgrass, salix, sugarcane bagasse, cotton seed hairs, leaves, bark, needles, logs, roots, saplings, short rotation woody crops, shrubs, switch grasses, trees and vines, and grains or grain processin wastes (e.g., wheat oat hulls, corn fines etc.). Additionally or alternatively, the lignin-containing biomass maybe derived from commercial or virgin forests, e.g., trees, saplings, forestry or timber processing residue, scrap wood such as branches, leaves, bark, logs, roots, leaves and/or products derived from the processing of such materials. The lignin- containing biomass may also be derived from the waste or byproduct streams from wood products, sawmill and paper mill discards and off-cuts, sawdust, and particle board) or from wood-related materials and woody wastes and industrial products, e.g., pul , paper (e.g., newspaper) papermaking sludge, cardboard, textiles and cloths, dextran, and rayon. Any suitable pyrolytic and/or hydrothermal upgrading techniques may be used to break down the lignin into smaller phenolic compound fragments.

In some embodiments, the phenolic compounds used in the process of the present invention may be provided in the aqueous fraction obtained after pyrolytic treatment and/or hydrothermal upgrading of lignin-containing biomass. The phenolic compounds may be used directly as provided in the aqueous fraction, or they may be concentrated in the aqueous fraction by any suitable means prior to use in the alkylation process. The aqueous fraction may comprise a mixture of phenolic compounds, or in particular, a mixture of phenolic compounds comprising at least two hydroxy! groups bonded to a aromatic hydrocarbon. The phenolic compounds may alternatively or additionally be purified and or separated from the aqueous fraction using any suitable techniques prior to use in the alkylation process. For example, the phenolic compounds may be separated from the aqueous phase using a suitable adsorbent, non-limiting examples of which may include alumina, aluminosilicates, and silica gel and recovered from the adsorbent using a suitable solvent, for example an organic solvent, non-limiting examples of which may include diethyl ether, cycjohexane, acetonitrile, ethanol, acetone, hexane, ethyl acetate, methylene chloride, etc., or a mixture of any two or more of these solvents. The phenolic compounds may be further purified and/or separated from each other in the aqueous fraction or once recovered from a suitable adsorbent prior to use in the alkylation process.

The phenolic compounds obtained from the aqueous fraction and/or obtained after separation and/or purification as described above may be the feedstock for the O-alkylation process of the present invention. Therefore, the feedstock may comprise water. In alternative embodiments, a feedstock comprising, phenolic compounds used for the process of the present invention may be free or substantially free of water.

The O-alkylation reaction feedstock comprising one or more phenolic compounds may be obtained as described above. Hence, the feedstock may also comprise other aromatic and/o aliphatic compounds, e.g., other aromatic and/or aliphatic compounds obtained from the pyrolytic treatment and/or hydrothermal upgrading of lignin-containing biomass. Non-limiting examples of other compounds that may be present in the feedstock include low -molecular weight aliphatics (C ₁ -C3 aliphati.cs including aliphatic acids such as formic or acetic acids, cyclohexanes and substituted cyclohexanes), phenol, guaiacol, substituted guaiacols, syringed, substituted syringols, substituted phenols, propylphenol, eugenol, other alkylated methyl aryl ethers, oxidised lignin monomers (syringaldehyde, vanillin, vanillic acid), aromatic diacids, β- ketoadipic acid, qoinones (hydroquinone, substituted hydroquinones) and aroroatics (benzene, toluene, xylene).

O-Alkyl thm

The reaction of Scheme 1 shows a non-limiting example of complete and selective O- methylation of .1.^2-benzenedioi. with two equivalents of a suitable alkylating agent (e.g., a methylating agent, dmiethylcarbonate, DMC) conducted in accordance with the present invention. The product of this reaction, .1 ,2-dmiethoxybenzene, represents the fully alkylated (dimethylated) product.

Scheme 1

Under experimental reaction conditions, the O-methylation of 1,2-benzenedioi in Scheme 1 may produce a mixture of products, e.g., a mixture comprising the monoalkyiated product, 2-methoxyp ^' henol (guaiacol); the dialkylated product, 1,2-dimethoxybenzene; and the reaction by-product, 1 ,3-benzodioxo1-2-one. Under experimental reaction conditions, the 0- alkyiation reactio of any phenolic compound comprising at least two hydroxy! groups may also yield a mixture of products e.g., a mixture comprising a monoalkyiated product and/or a dtalkylated product and/or a triaikyiated product, etc. As such, the alkylation process according to the present invention may encompass the dialkylatton of phenolic compounds, wherein the phenolic compounds comprise one or more beozenediol compounds or substituted benzenedtol compounds as described in the section entitled 'Phenolic Compounds', and wherein the major reaction products comprise di alkylated products (i.e., aryl-alkyl di ethers). The alkylation process may also encompass trialkylation of phenolic compounds, wherein the phenolic compounds comprise one or more benzenetrtoi compounds or substituted benzenetriol compounds as described in the. section entitled ' Phenolic Compounds', and wherein the major reaction products comprise triaikyiated products (i.e., aryl-alkyl tri ethers). The alkylatio process may further encompass the complete alky lation of phenolic compounds, wherein the phenolic compounds comprise one or more compounds comprising four, five or six hydroxy! groups, or more than four, five or six hydroxy! groups. The alkyiation process may additionally encompass the complete alkyktion of phenolic compounds, wherein die phenolic compounds comprise a mixture of any one or more of benzenediol compounds, substituted benzenediol compounds, benzenetriol compounds, substituted benzenetriol compounds, compounds comprising four, five or six hydroxy! groups, or compounds comprising more than four, five or six hydroxy! groups, as described in the section entitled 'Phenolic Compounds', and wherein the alkyiation produces as major products fully alkylated phenolic ethers.

As described above, the "major product" may be the fully or completely alkylated product and the remaining reaction products, including the partially alkylated products, may be the minor products. The alkyiation process according to the invention may result in a total yield of major (or fully alkylated) products that is greater than the total yield of minor prod ucts. It may also result in a yield of major (fully alkylated) and minor products in a ratio of greater than about 1000; 1 , or greater than 500: 1 , or greater than 100; 1 , or between about 100; 1 and about 40; I , or between about 100; 1 and 80; 1 , 90; 1 and 50: 1 , 80: 1 and 40: 1 , or about 1000: 1 , 500: 1 , 100: 1 , 80: 1 , or 50: 1. The alkyiation process according to the invention may result in a yield of the fully alky lated product of about 95%, or between about 99% and 90%, or 95% and 85%, 95% and 75%, 80% and 60%, or about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 99%. The alkyiation process according to the invention may result in a negligible or substantially negligible total yield of minor (or partially alkylated) products or other reaction by-products, e.g., the negligible yield may be less than 5%, or between about 0.1% and 1%, o 1% and 5%, or 0.1 % and 3%, or about.0.1 %, 0.5%, 1%, 2%, 3%, 4% or 5%. The alkyiation process according to the invention may result in a conversion from the starting material to the fully alkylated product of about 95%, or between about 99% and 90%, or 95% and 85%, 95% and 75%, 90% and 60%, or about 60, 70, 75, 80, 85, 90, 95 or 99%.

The process of the present invention provides several advantages over known processes. One advantage of completely alkyl ating phenolic compounds comprising two or more hydroxy! groups is the increase in melting point of the resultant phenolic ethers with respect to the phenolic compounds or incompletely alkylated phenolic compounds. Increases in melting point, such that the phenolic ethers are liquids at room temperature, are favourable, tor example, in fuel additive and blending applications. Another advantage of completely alkylating phenolic compounds comprising two or more hydroxvl groups is that the resultant phenolic ethers may be less corrosive than the phenolic compounds or incompletely alkylated phenolic compounds. Tmnsesterification

It will be understood by persons skilled in the art that the alkylating agents described in the following section may react with a phenolic compound comprising at least two hydroxy! groups and a base catalyst as described below in a transesterifieation reaction. It wil l also be understood that certain conditions may favour the transesteritlcation reaction and its products over the O-alkylation reaction and its products. In accordance with the present invention, conditions favouring the O-alkylation reaction may be selected. In particular, conditions may be chosen such that yields of multiply alkylated alkyl-aryl ether prod ucts, and in particular completely alkylated alkyl-aryl ether products, as described in the following sections, are achieved.

Alkylating agents

The process of the present invention for O-alkylation of phenolic compounds comprises reacting the phenolic compounds with an alkylating agent. The process may employ any suitable alkylating agent. The alkylating agent used in the process of the present invention may be capable of alkylating any one or more phenolic compounds described herein comprising at least two hydroxy! groups (for example, those set out in the section entitled 'Phenolic

Compounds'). Non- limiting examples of suitable alkylating agents may include organic/alky 1 sulfates, carbonates and halides, methanol, or A V-dimethySformamide dimethylacetal.

Advantageousl , an organic carbonate may be used in the invention as an alkylating agent, as organic carbonates are relatively non-toxic compared to alternative organic sulfate or organic halide alkylatin agents. The organic carbonate alkylating agent may be, for example, a dialky carbonate, an aryl-atkyl carbonate, or an a1keny1~alkyl carbonate. The alkylating agent alky! group may be independently selected from a group comprising linear, branched or cyclic Ci_s alky! groups, e.g., a methyl, ethyl, propyl, isopropyl, or cyclohexyl group. The alkylating agent aryl group may be a phenyl group or substituted phenyl group. The alkylating agent alkenyl group may be any linear, branched or cyclic Ci^ alkenyl group, e.g. an allyl group. Non- limiting examples of alkylating agents include dimethyl carbonate, diethyl carbonate, dipropy! carbonate, diisopropyl carbonate, dicyclohexyl carbonate, methyl-2-(2-methoxyethoxy)ethyl carbonate, ethylmethyi carbonate, propylmethyl carbonate, allylmethyl carbonate,

cyclohexyl methyl carbonate, phenylmethyl carbonate, or a combination of any one or more of the preceding alkylating agents.

The process for O-alkylation of phenolic compounds, comprising reacting one or more phenolic compounds described in the section entitled 'Phenolic Compounds' with one or more alkylating agents described above, may therefore produce a variety of aryl ether and substituted nd ether products. Fully alkylated products may include atkyl-aryl. ethers (including eye tea 1 kyl -aryl ethers) .

The molar ratio of the phenolic compound to the alkylating agent used in the process of the invention may depend on the composition of the reactant mix ture, in particular, it may depend on the number of hydroxy! groups bonded to the aromatic hydrocarbon in the phenolic compounds under treatment. The number of moles of alkylating agent may be equal to or greater than the number of moles of hydroxy! groups in the reactant mixture so that complet alkylation of the hydroxy! groups ma y be effected. Advantageously, a particular ratio of hydroxy! groups to alkylating agent may be chosen to produce yields of the completely alkylated product as described in the section entitled 'O-alkylation'. When the reactant mixture comprises benzenediois and/or substituted benzenediols, the molar ratio of benzenediol compound to alkylating agent compound may be about 1 : 15, or may be between about 1 :30 and 1 :5, e.g. between about 1 :25 and 1 : 10, 1 : 15 and .1 :8, 1 :20 and 1 : 10, or 1 .10 and 1 :5, or may be about 1 :30, 1 :25, 1 :20, 1 :15, 1:10, or 1:5. A molar ratio of benzenediol compound to alkylating agent compound of about 1:13 or above, for example, a catechol. DMC ratio of 1:1.3 or above, is ad vantageous for producin the Ms-methylated product in yields of about 90% or greater.

Where the reactant mixture comprises benzenetriols and/or substituted benzenetriols. the molar ratio of tool compound to alkylating agent compound may be about 1 : 15, or may be between about 1 :30 and 1 :5, e.g. betw een about 1:25 and 1:10, 1 : 15 and 1 :8, 1:20 and 1: 10, or 1: 10 and 1 :5, or may be about 1 :30, 1 :25, 1 :20, 1 : 1 , 1 : 1.0, or 1 :5. Where the reactant mixture comprises a mixture of benzenediols, benzenetriols, and/or compounds comprising four, five or six hydroxy! groups, or compounds comprising more than four, five or six hydroxyl groups, the molar ratio of hydroxyl groups to alkylating agent may be about 1 :30, or may be between about 1 :60 and 1 : 10, e.g. between about 1 ;50 and 1. :20, 1 :30 and 1 : 15, 1 :40 and 1 ;20, or 1 :20 and 1 : 10, or may be about 1:60, 1 :50, 1 :40, 1 :30, 1:20, or 1 : 10.

Bases

The process for O-alkylation of phenolic compounds, comprising reacting phenolic compounds with an alkylating agent, may further comprise providing a base. The base may be added to the reaction mixture, where it may function as a catalyst in the reaction, and ma therefore be regenerated at the completion of each reaction cycle. The base may soluble in the reaction mixture or it may be insoluble in the reaction mixture. Where the base is insoluble in the reaction mixture, this may correspond to the base having a solubility of less than about 1 g base per mL of solvent, between about 1 g/mL and about 0.0001 g/mL, or between about 1 g/mL and about 0.1 g mL, or between about 0.5 g/mL and about 0.0! g mL, or between about 0.01 g/mL and about 0.0001 g/mL, e.g., less than about 0.5 g/mL, or less than 0.1 g/m ^' L, or less than about 0.01 g mL, or less than about 0.001 g mL, e.g., about 1, 0.5, 0.1, 0.05. 0.01 , 0.005, 0.001 , 0.0005, or 0.00 1 g/mL. Where the base is soluble or substantially soiuble in the reaction mixture, this may correspond to the base having a solubility of more, than about 1 g base per mL of solvent, e.g. , between about I g/mL and about 10 g/mL, or between about 5 g/mL and 20 g/mL, e.g., more than 1 g mL, 5 g/mL. 10 g/mL, 15 g/mL or 20 g/mL, e.g., about 1 g/mL, 3 g mL, 5 g/mL, 7 g/mL, 1.0 g/mL, 15 g/mL or 20 g/mL. The base may be insoluble at room, temperature (e.g., 20 °C) but may be soluble at reaction temperature (e.g., 170 °C). The base may therefore be a homogeneous base or a heterogeneou base. The base may be any suitable base, and may include, for example, a group I hydroxide, a group I or 11 carbonate, a group 1 alkoxide or aryloxide, a group 1 hydrogen carbonate, a transition metal oxid or a trialky!amine. Non-limiting examples of suitable bases may include potassium hydroxide, lithium hydroxide, sodium hydroxide, aluminium hydroxide, potassium carbonate, caesium carbonate, calcium carbonate, sodium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, manganese dioxide, trietliylamine, or compounds of the nature MOR, where M is Li, Na, K or Tl and R is an aliphatic group, e.g., methyl, ethyl, propyl isopropyl, /i?r/-butyl, or aryl. Suitable bases may also incl ude pyridine, 1,4- diazabicycto[2,2.2]octane, and LS-diazabicycloimdec-T-ene (DBU). The base may also be red mud, wherein the components of red mud expressed in approximate percentage by mass may be: sodium carbonate (<5%), sodium hydroxide ( 1%), iron (II) oxide (60%), aluminium oxide (1.5%), sodium aluminosilicate (<S%), titanium oxide (5%), silicon dioxide (<}%). The red mud may be substantially or completely dried or dehydrated prior to use in alkylation reactions.

The base utilised may be one that does not degrade or substantially degrade upon exposure to air. It may be chosen such that it does not react or substantially react with any atmospheric gases or atmospheric moisture. The base may advantageously be capable of repeated exposure to air with no loss of catalytic activity, or no substantial loss of catalytic activity, in the O-alkylation reaction.

In embodiments where the reactant mixture comprises any one or more ofbenzenediols, benzenetriols, and/or compounds comprising four, five or six hydroxy! groups, or compounds comprising more than tour, five or si hydroxy! groups, the molar ratio of hydroxy] groups to base may be about 1 : 1 , or may be between about 10: 1 and 1 : 10, e.g. between about 10: 1 and 1 : 1, 1 : 1 and 1 : 10,. or 5: 1 and 1 :5, or may be about 10:1, 5: 1, 4: 1 , 3:1 , 2:1, 1 : 1, 1 :2, 1 :3, 1 :4, .1 :5 or 1:10. The molar ratio of hydroxyl groups:aIkylating age.nf.base used in the process of the invention may depend on the composition of the reactant mixture, e.g., the ratio of hydroxyl groups:alk.y1ating agents as described in the section entitled 'Alkylating agents', or the ratio of hydroxyl groups: base as described above.

The reaction mixture used in the O-alkylation process of the i nvention, compri sing reacting phenolic compounds with an alkylating agent in the presence of a base, may comprise phenolic compound and an. alkylating agent as described in the sections entitled ' Phenolic Compounds ¹ and 'Alkylating agents' respectively, and a base as described above, and may further comprise water. As water may decompose the alkylating agent or slow down the aikylation reaction, it is advantageous for the process of the present in vention to produce the high yields of completely alkylated products described in the section entitled O-alkylation' when the reaction mixture further comprises water. In some embodiments, the water may originate from the pre-processing of the phenolic compound feedstock, in some embodiments, the water may be atmospheric water incorporated into the reaction mixture. In some

embodiments, the water may be a component of the solvent in which the aikylation reaction is conducted. The ra tio of moles of water to moles of phenolic compounds present in the reaction mixture during the aikylation reaction may be between about .1 50 and about 50: 1 , or between about 1 ;50 and about. 1: 10, 1 :3Q and 1 : 1 , .1 : 1 and 20; 1 , 10; 1 and 50: 1 , or 40: 1 and 50; 1 , or about 1 :50, 1 :20, 1 : 1 , 1 : 1 , 5: 1 , 10: 1 , 20: 1 , and 50: 1. Reaction mixtures having a watenphenoiic compound ratio of about 3:1 may advantageously produce completely alkylated products with conversions of greater than about 70%. increasing the reaction time by a factor of at least 2, or between about 2 and 10 times, or between about 2 and about 5, or about 4 and about 8, or about 10 and about..10, e.g., about 2, 3, 4, 5, 6, 7, 8, 9, or 10 times may advantageously increase the conversion to greater than about 80%.

Solvents

A reaction mixture used in the O-alkylation process of the invention, comprising reacting phenolic compounds with an alkylating agent in the presence of a base, with or withou t water, may further comprise a solvent. The presence of a sol vent may be advantageous in that the selected phenolic compounds and alkylating agents, as described in the sections entitled

"Phenolic Compounds' and 'Alkylating agents' respectively, may be particularly soluble in the solvent. The solvent may be chosen such that the selected, phenolic compounds may be at least sparingly soluble in the solvent. The solvent may also soluhilise the base. The solvent may be miscibie with water, or water may be slightly soluble in the solvent Where microwave irradiation is used to heat the reaction mixture, the solvent may be advantageously chosen such that the dielectric properties of the reaction mixture may be controlled and therefore the temperature of the reaction mixture ma be moderated. Where microwave irradiation is used to heat the reaction mixture, the solvent may be polar. Under certain conditions, including when the reaction mixture contains polar reactants or ions, microwave transparent solvents may be used. Under such conditions, reactant concentrations may be sufficientl high as to moderate the absorption of microwave radiation by the reaction mixture. The solvent may be any suitable solvent including, for example, an organic solvent. The organic solvent may be a polar protic or aprotic solvent. Non-limiting examples of suitable solvents include water, acetonitrile (MeCN), xylene, dimethylsulfoxtde, triethylene glycol dimethyl ether (triglyme), di methyl formamide, A ^: -methyl-2-pyrrolidone (N P), methanol, ethanol, and ferZ-butanol, or a mixture of any two or more of these. Non-limiting examples of microwave transparent solvents include toluene, dioxane and tetrahydrofiiran. The base may or may not be soluble in the so lvent.

Reaction parameters

The O-alkylation process of the present invention, comprising reacting the phenolic compounds with an alkylating agent in the presence of a base, with or without water, may generally require heating to a desired reaction temperature. Heating the reaction mixture to a temperature of at least about 160 °C may advantageously favour the -alkylation reaction over competing or alternative reactions, e.g> , carboxyalkylation. The reaction mixture may be heated to a temperature of at least about 160 °C, or least about 170 °C, between about 160 °C aid about 200 °C, between about 160 ° and about 180 °C, between about 170 °C and about 200 ° , or about 160 °C, 170 °C 180 °C, 90 ^CJ C or 200 °C, A reaction temperature as disclosed herein may represent an approximate average temperature of the reaction mix ture over a set time period {i.e., a reaction time). In some embodiments, the temperature may be varied throughout the alleviation reaction process, e.g.. the temperature maybe gradually increased. Reaction temperatures of at least about 170 °C, or temperatures of between about 170 °C and about 200 °C may advantageously produce yields of completely alkylated products of greater than about 85% and produce substantially no partially-alky!ated products. The heat may be provided to the reaction mixture using conventional heat sources or an other suitable method. For example, the heat may be generated by microwave irradiation of the reaction mixture. Microwave irradiation advantageously heats the reaction mixture more quickly arid efficiently than conventional heat sources and can thereby speed up the reaction rate. Microwave irradiation may also cause localised areas of the reaction mixture to achieve higher temperatures than the average temperature of the reaction mixture described above. The microwave irradiation may be provided to the reaction mixture by any suitable microwave source, e.g., a focusse microwave. Any suitable focusse microwave may be used, for example, the focussed microwave may be a batch microwave or a .flow microwave. Where a batch microwave is used, the reaction mixture may be stirred during irradiation using any suitable apparatus to assist with even heat distribution. The rate of stirring may be greater than about 300 rpm, or greater than about 600 rpra, or between about 300 and about 1200 rpm, or between about 300 and 600, 600 and 900, 900 and 1200 rpm, or about 300, 600, 900, 1 100 or 1200 rpm. Where a flow microwave is used, the reaction mixture may be pressurised or pumped through any suitable continuous reactor vessel. Reactor volumes, flow rates., and residence times may be calculated for specific microwave instruments by those skilled in the art using, for example, instrument-specific software and/or manuals. By way of non-limiting example, reaction mixture flow rates of between about 0.1 mL/min and about 50 mUmin may be used, for example, flow rates of between about 0.1 mL/min and about 0.5 ml min, or between about 0.5 mL min and about 1.0 mL min, or between about 1.0 mL/min and about 5 mL/min, or between about 5 mL/min and about 0 mL min, or between about 10 mL min and about 25 mL min, or between about 25 mL/min and about 50 mL min may be used, e.g., a flow rate of about 0.1 , 0.25, 0.5, 1.0, 2.5. 5.0, 10.0, 20.0 or 50.0 mL/min may be used. A reactor volume of between about 5 mL and about 750 mL may be used, e.g., a volume of between about 5 mL and about 100 mL, or between about 100 mL and about 250 mL, or between about 250 mL and about 500 mL may be used, e.g., a volume of about 5 mL, about 10 mL, about 50 mL, about 100 mL, about 150 mL, about 200 mL, about 250 mL, about 500 L, or about 750 mL may be used. A backpressure of at least about 350 psi may be used.

The reaction time and/or residence time for the O-alkylation process of the invention may be any suitable period in which -alky lation of hydroxy! groups may be achieved. The reaction time and/or residence time may be advantageously chosen to produce the high yields of multiply alkylated products, and in particular completely alkylated products, described in the section entitled 'Phenolic Compounds'. For example, the reaction time and/or residence time may be between about 5 mm and about 600 min, or between about 5 min and about 240 min, or 120 and 360, or 240 and 480 mm, or 420 and 600 mm, or about 5, 10, 20, 40, 60, 80, 100, 120, 150, 180, 220, 240, 300, 360, 420, 480, 540 or 600 min. Reaction time and/or residence time may be adjusted according to the temperature of the reaction, e.g., for a batch microwave reactor, reaction times of between about 20 and 120 minutes may be used when the reaction is heated to a tempera ture of more than abo ut 170 °C, or a reaction ti me of between 60 and 240 minutes .may be used when the reaction is heated to a temperature of between, about 360 °C and about 170 °C. For a flow microwave reactor, residence times of between about 1 minutes and about 25 minutes maybe used when the reaction is heated to a temperature of between about 170 °C and about 200 ( ^' . It will be understood that references herein to a 'reaction time' may refer to a 'residence time', wherein the time corresponds to the time the reaction mixture is exposed to microwave radiation.

A reaction vessel used to conduct the 0-alkylation process of the invention may be sealed during heating and/or irradiation and therefore may be subject to autogenous pressure. The reaction mi xture ma be under a pressure, autogenous or otherwise, of between about 1 and about 30 bar, or between about 1 and 8, 5 and 12, 10 and 16, 15 and 25, or 22 and 30 bar, or at least 5, 1 , 12 or 15 bar, or about. 1, 5, 7, 10, 12, 14, 16, IS, 20, 22, 24, 26, 28 or 30 bar.

Alternatively, a reaction vessel used to conduct the 0-al kylation process of the invention may be a continuous reaction vessel, in which case the reaction mixture may pressurised by, e.g., a pump or other mechanism, to drive the reaction mixture through the reaction vessel in a continuous manner. The reaction mixture may be under a pressur e as described in this paragraph,

A reaction mixture used in the 0-alkylation process of the invention may have a pH of more than 7, more than 10, more than 12, or more than 14, e.g. , a pH of 10, 1 1 , i 2, 13 or 14. The pH of the reaction mixture may be chosen such that it is greater than the ¾ of any one or more of the OH groups of the phenolic compound.

A combination of parameters described above including, but not limited to, reaction temperature, heating method, stir rate, residence time, microwave power, flow rate, reaction time and reaction pressure, may be chosen such that yields of multiply alkylated products, and in particular completely alkylated products, as described in the section entitled Ό-alkylation', are achieved. These parameters may also be modified according to the choice of 0-alkylation reaction specific parameters, including but not limited to solvent, base, phenolic compound/phenolic compound mixture and alkylating agent such that yields of multiply alkylated products, and in particular completely alkylated products, as described in the section entitled ' Phenolic Compounds', are achieved.

Reaction cycles

The O-alkylation. process of the invention may further compri se separating the base from any one or more of (i) the alkylating agent; ( ii) the phenolic compound; and (iii) an 0-alkylated phenolic compound, onl subsequent to the phenolic compound undergoing O-alkylation according to the reaction, it will be understood that all phenolic compounds present in a given feedstock need not have undergone O-alkylation before the base is separated.

The separating may be performed using any suitable method, for example, filtration or eentrifugation. Filtration may be performed using any suitable filtration aid, for example, activated charcoal or celite. The filtrate or supernatant solution comprising the alkylating agent and/or the phenolic compound may be subsequently separated from the reaction products, solvent and/or any other component of the reaction mixture using any suitable method, e.g., by using a suitable adsorbent, non-limiting examples of which may incl ude alumina,

aluminosilicates, and silica gel, and recovering the separated components from the adsorbent using a suitable solvent, for example an organic solvent, non-limiting examples of which may include diedry! ether, cyclohexane, aeetonttrile, ethanol, acetone, hexane, ethyl acetate, methylene chloride, etc., or a mixture of any two or more of these solvents. The alkylating agent, phenolic compound, product and/or solvent components may be additionally or

alternatively separated by distillation or fractional distillation. As the base utilised may be one that does not degrade or substantially degrade upon exposure to air, it may not react or not substantially react with any atmospheric gases or atmospheric moisture. The base may be capable of repeated separation and/or exposure to air with no loss of catalytic activity, or substantially no loss of catalytic activity, in subsequent -alkylation reactions.

The O-alkylation process according to the invention may further comprise, subsequent to an initial O-alkylation reaction, contacting the base with an addi ional phenolic compound and an additional alkylating agent, wherein the additional phenolic compound comprises a plurality of hydroxyl groups bonded to an aromatic hydrocarbon; and, reacting the additional phenolic compound, the additional alkylating agent, and said base at a further suitable reaction temperature and for a further suitable time period for O-alkylation. of the plurality of hydroxyl groups. The base may be separated from other components as described in the two paragraphs directly above prior to use in the subsequent O-alky!ation reaction. Alternatively, the additional phenolic compound and the additional alkylating agent may be applied directly to the mixed product of the initial reaction.

The additional phenolic compound comprising a plurality of hydroxy! groups may be, for example, a phenolic compound as described in the section entitled 'Phenolic Compounds' . The phenolic compound and the additional phenolic compound ma be identical or may be different.

The additional alkylating agent may be an alkylating agent as described in the section entitled ' Alkylating agents'. The additional alkylating agent and the alkylating agent may be identical, or ma be different.

The base may be identical to the base used in the initial O-alkylation reaction. The base may be the same as the base used in the O-atkylating process of a phenolic compound comprising at. least two hydroxy} groups bonded to an aromatic hydrocarbon, where the process comprises reacting tire phenolic compound with an alkylating agent in the presence of a base, at a suitable reaction temperature and for a suitable time period, thereby 0-alkylating the at least two hydroxy! groups. The base may be separated from the other reaction mixture components, e.g _r , the alkylating agent and/or the phenolic compound as described above prior to re-use. Alternatively, the base may be re-used without first being separated from the reaction mixture or components thereof.

The further suitable reaction temperature may be a reaction temperature as described in the section entitled 'Reaction parameters'. The further suitable reaction temperature and the reaction temperature may be identical, or may be different

The further suitable time period may be a time period as described in the section entitled 'Reaction parameters'. The further suitable time period and the time period may be identical, or may be different.

The O-alkylation of the plurality of hydroxy! groups may encompass the dialkylation of the additional phenolic compounds and wherein the major reaction products comprise diaikylated products (i.e., aryl-a!ky! diethers) as described in the section entitled O-alkylation'. The O-alkylation of the plurality of hydroxyl groups may further encompass the complete alkyialion of the additional phenolic compounds. The O-alkylation process further comprising contacting the base with an additional phenolic compound and an additional alkylating agent subsequent to the O-alkylation reaction, may yet further comprise reacting the additional phenolic compound, the additional alkylating agent, and said base in the presence of either additional water or an additional organic or inorganic solvent. It may yet further comprise reacting the additional phenolic compound, the additional alkylating agent, and said base in the presence of both additional water and an additional organic or inorganic solvent.

The additional solvent may be a solvent as described in the section entitled 'Solvents'. The additional solvent and the solvent may be identical, or may be different.

The additional water m ay ori ginate from the pre-processing of the additional phenolic compound feedstock. In some embodiments, the water is atmospheric water incorporated into the reaction mixture. In some embodiments, the water i s a component of the additi onal sol vent in which the alkylation reaction is conducted. The ratio of moles of additional water to moles of additional phenolic compounds present in the reaction mixture during the alkylation reaction may be as described in the section entitled 'Bases'.

When the -alkylation process of the invention further comprises separating the base from any one or more of fi) the alkylating agent; fii) the phenolic compound; or (iii) an O- alkylated phenolic compound subsequent to the O-alkylation reaction, the O-alkylation process may yet further comprise conducting between 1 and 100 cycles of the process subsequent to the O-alkylation reaction, each cycle comprising contacting said base with an additional phenolic compound and an additional alkylating agent, wherein the additional phenolic compound comprises a plurality of hydroxyi groups bonded to an aromatic hydrocarbon; and, reacting the additional phenolic compound, the additional alkylating agent, and said base at a further suitable reaction temperature and for a further suitable time period for O-alkylation of the plurality of hydroxyi groups. The O-alkylation cycle may be performed once, or may be repeated such that the total number of reaction cycles is more than 1 , 2, 5, 10, 15, 20. 25, 50 or 100, e.g., the total number of reaction cycles may be between I and 100, 10 and 50, 40 and 80, 60 and 100, o 1 , 2, 5, 10, 15, 20, 25, 50, 75, or !OO. Cycling the O-alkylation process in this way may

advantageously avoid unnecessary purification of the catalyst between reactions, and may advantageously avoid a loss in acti vity of the catalyst or a reduction in the yi eld of the completely alkylated product. 0-Alkylation Products

The process of O-alkylation of phenolic compounds described herein may encompass monoalkylation, i.e.,, conversion of at least one hydroxyl group directly bonded to an aromatic hydrocarbon in a phenolic compound to an aryl-alkyl ether by reacting the at least one hydroxyl group with at least one equivalent of an alkylating agent The O-alkylation process may also encompass multiple alkylation, for example, dialkylation, ie. ₇ conversion of two hydroxy! groups directly bonded to an aromatic hydrocarbon in phenolic compound to an aryl-alkyl diether b reacting the two hydroxyl groups with at least two equivalents of an alkylating agent. The O-alkylation process may further encompass triaikylation, i.e., conversion of three hydroxyl groups directly bonded to an aromatic hydrocarbon in a phenolic compound to an aryl-alkyl triether by reacting the three hydroxyl groups with at least three equivalents of an alkylating agent. The O-alkylation process may encompass the alkylation of four, five, or six hydroxyl groups directly bonded to aromatic hydrocarbon in a phenolic compound to form compounds comprising four, five, six aryl-alkyl ether moieties respectively, or may comprise the alkylation of all hydroxyl groups directly bonded to an aromatic hydrocarbon in a phenolic compound.

Multipl alkylated products, and particularly completely alkylated products, produced by the process of the present invention may be further processed for use, for example, in fuel additive and blending applications. The further processing may comprise separating the completely alkylated alkyl-aryl ethers from the partially alkylated alkyl-aryi ethers and other reaction by-products. Any suitable separation and/or purification technique ca be used.

The completely alkylated products may be separated from any partially alkylated alkyl-aryl ethers and other reaction by-products using any suitable technique or method. For example, the completely alkylated products may be separated from the reaction by-products using a suitable adsorbent, non-limiting examples of which include alumina, aluminosilicates, and silica gel. The products may then be recovered from the adsorbent using a suitable solvent, for example an organic solvent , non-limiting examples of which include diethyl ether , cyciohe ane, acetonitrile, ethanol, acetone, hexane, ethyl acetate, methylene chloride, etc., or a mixture of any two or more of these solvents. The completely alkylated products may be additionally or alternatively separated from the reaction by-products by distillation or fractional distillation. Distillation may allow the lower boiling point completely alkylated aryl-alkyl ether products to be recovered separately from the higher boiling point partially alkylated aryl-alkyl ether products and/or phenolic compound starting materials and/or other reaction by-products. Separation of the completely alkylated products from partially alkylated alkyl-ary l ethers and other reaction by-products offers advantages for fuel blending applications, as completely alkylated products have more favourable physical characteristics, e.g., lower boiling points compared to the boiling points of the phenolic compound starting materials, and more favourable chemical characteristics, e.g., they may be less corrosive than either partially alkylated products or other reaction by-products .

Exemplary reacthn conditions

In certain embodiments, the phenolic compounds treated in accordance with the present invention comprise an aromatic hydrocarbon to which two hydroxy! groups or more than two hydroxy! groups are be directly bonded. Accordingly, when the aromatic hydrocarbon group is benzene, the phenolic compounds are benzenediols. Preferably, the benzenediols are imsubstituted or alkyl- or alkoxy-substitiited benzenediols, e.g., methyl, ethyl, propyl, isopropyl, butyl, isobutyl, or any other linear or branched C. alkyl group substituted benzenediols, or mefhoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, or any other linear or branched C.i-s alkoxy group substituted benzenediols. The benzenediols may be hydroxy-substituted benzoic acid, or hydroxy substituted benzaldehyde, or hydroxy substituted acetophenone.

By way of non-limiting example only, phenolic compounds used in the process of the present invention may be provided in an aqueous fraction obtained ftom the pyrolytic treatment and/or hydrothermal upgrading of lignin-containing biomass. The phenolic compounds may be used directly as provided in the aqueous fraction, or more preferably, they may be separated from the aqueous phase using a suitable adsorbent, e.g., alumina, and recovered from the adsorbent using a suitable solvent, e.g., diethyl ether.

The O-alkylatton process may be performed by reacting one or more phenolic compounds with an alkylating agent in the presence of a base to form one or more aryl-alkyl ethers. The mixture may also comprise a solvent. Optionally, the reaction mixture may comprise water.

The .mixture of phenolic compounds used as feedstock in the O-alkylation reaction preferably comprises one or more benzenediol compounds or substituted benzenediol compounds.

Preferably, the alkylating agent used in the invention is an organic carbonate, e.g., a di alkyl carbonate, an aryl-alkyl carbonate, or an alkenyl-alkyl carbonate. More preferably, the alkylating agent ma be dimethyl carbonate, diethyl carbonate or di propyl carbonate. Preferably, the base used in the invention is insoluble in the reaction mixture, e.g., it may have a solubility of less than about 1 g base per ml of solvent, e.g. between about 1 g/hiL and about 0.01 g/niL. The base may therefore be a heterogeneous base. Preferably, the

heterogeneous base is a group 1 hydroxide or a group I or II carbonate. For example, the base may be potassium hydroxide or caesium carbonate.

The reaction mixture may comprise a solvent, in which the phenolic compounds under treatment are at least sparingly soluble. Preferably, the solvent is polar, e.g., is a polar organic solvent. For example, the solvent may be acetonitrile.

When the reactant mixture comprises benzenediols and/or substituted benzenediols, the molar ratio ofbenzenediol compound to alkylating agent compound may be about 1:15, or preferably between about 1 :20 and 1: 10. The molar ratio of hydroxy, groups to base in the O- alkylation reaction mixture may be about 1:1, preferably between about 5: 1 and 1 :5.

The temperature of the reaction mixture during the O-alkylation process may be at least about 160 °C. For example, the temperature of the reaction mixture may be at least about 170 °C. The heat is may be provided to the reaction mixture by microwave irradiation of the reaction mixture. For example, the heat may be provided to the reaction mixture using a focussed microwave, e.g., a batch microwave or a flow microwave.

The O-alkylation reaction mixture may be stirred during microwave irradiation using any suitable apparatus. The rate of stirring is may be, for example, about 600 rpm, or at least about 600 rpm.

The O-alkyiation reaction ma take between about 20 min and about 240 mill, but may be adjusted according to the temperature of the reaction, e.g., reaction times of between about 20 and 120 minutes may be used when the reaction is heated to a temperature of more than about 170 °C, or a reaction time of between 60 and 240 minutes may be used when the reaction is heated to a temperature of between about 160 °C and about 170 °C.

The O-alkylation reaction may take place under autogenous pressure. Such pressure may be, for exam le, between about 10 and 30 bar.

The O-alkylation process may produce monoalkyiated products and/or multiply alkylated products including, for example, dialkylated products. Preferably, the major product(s) of the O-alkylation reaction comprise fully or completely alkylated aryl-alkyl ethers, e.g.. aryl-alky] diethers, triefhers, etc. More preferably, the alkylation process may result in a total yield of major (or fully alkylated) products that is greater than the total yield of minor (rrtonoalkylated or other by-product) products. Still more preferably, the alkylation process may result in a yield of major (fully alkylated) and minor/by- products in a ratio of greater than about 1000: 1 , or greater than 500: 1 , or greater than 100: l. _s or between about 1000:1 and 500:1.

The O-alkylation process of the invention may further comprise separating the base from either or both of (i) the alkylating agent and the phenolic compound; or, (ii) the phenolic compound, subsequent to the O-alkylation reaction.

The O-alkylation process according to the invention may further comprise, subsequent to the -alkylation reaction, contacting the base with an additional phenolic compound and an additional alkylating agent, wherein the additional phenolic compound comprises a plurality of hydroxy! groups bonded to an aromatic hydrocarbon; and, reacting the additional phenolic compound, the additional alkylating agent, and said base at a further suitable reaction

temperature and for a further suitable time period for O-alkylation of said plurality of hydroxy! groups.

The phenolic compound and the additional phenolic compound ma be identical or may be different. For example, the additional phenolic compound may comprise an aromatic hydrocarbon to which two hydroxy! groups o more than two hydroxy! groups are be directly bonded. Accordingly, when the aromatic hydrocarbon group is benzene, the additional phenolic compounds are benzenediols. Preferably, the benzenediols are iinsubstituted or alkyl- or aikoxy-substituted benzenediols, .g., methyl, ethyl, propyl, isopropyi, butyl, isohuty!, or any other linea or branched Cj„s alkyl group substituted benzenediols, or methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobtitoxy, or any other linear or branched C _\ , _% alkoxy group substituted benzenediols. The benzenediols may be hydroxy-substituted benzoic acid, or hydroxy substituted benzaldehyde, or hydroxy substituted acetophenone.

The additional al kylating agent and the alkylating agent may be identical, or may be different. For example, the additional alkylating agent may be an organic carbonate, e.g., a dialkyl carbonate, an aryl-alky! carbonate, or an alkenyl-alky! carbonate, More preferably, the additional alkylating agent may be dimethyl carbonate, diethyl carbonate or dipropyl carbonate.

The base may be separated from the other reaction mixture components, e.g., the alkylating agent and/or the phenolic compound prior to re-use. The base may be re-used without first being separated from the reaction mixture or components thereof. The further suitable reaction temperature and the reactio temperature may be identical, or may be different. For example, the further suitable reaction temperature may be at least about 170 °C.

The further suitable time period and the time period may be identical or may be different. For example, the further suitable time period may be between about 20 min and about 240 min.

The O-alkylation process further comprising contacting the base with an additional phenolic compound and an additional alkylating agent subsequent to the O-alkylation reaction, may yet further comprise reacting the additional phenolic compound, the additional alkylating agent, and said base in the presence of additional water and/or an additional organic or inorganic solvent.

The additional solvent and the solvent may be identical, or may be different. For example, the additional solvent may be polar, e.g. , a polar organic solvent. For example, the additional solvent may be acetonitrile.

When the O-alkylation process of the inventi on further comprises separating the base from any one or more of (i) the alkylating agent; (ii) the phenolic compound; or (Hi) an O- alkylated phenolic compound subsequent to the O-alkylation reaction, the O-alkylation process may yet further comprise conducting between 1 and 100 cycles of the process subsequent to the O-alkylation reaction, each cycle comprising contacting said base with an additional phenolic compound and an additional alkylating agent, wherein the additional phenolic compound comprises a pl urality of hydroxy} groups bonded to an aromatic hydrocarbon; and, reacting the additional phenolic compound, the additional alkylating agent, and said base at. a further suitable reaction temperature and for further suitable time period for O-alkylation of the plurality o hydroxy! groups.

Examples

The present invention will now be described with reference to specific examples, which should not be construed as in any way limiting.

Microwave

The Anton Paar Monowave 300 microwave synthesis reactor used in the Examples below has a magnetron frequency of 2455 MHz; power consumption of 1600 VA; and an AC 230 V ± 10% 50 Hz/60Hz power supply. Example 1: Methylatwn of benzenediols with ditneihykarbonaie under microwave conditions Procedure: A solution of substrate (1.82 mmol; Table 1), DBU (1 equiv/OH), DMC (2 mL), and C¾CN (2 mL) was heated in a Anton Paar Monowave 300 microwave synthesis reactor at 1.60 °C at approximately 20 bar with a stir rate of 600 rpm. The reactio products were analysed by GC-FI and GC-MS. Results are shown in Table 1.

*1 eqniv ofTBAI was also charged to the reaction mixture before heating in. the reactor. TBAI may act as a phase transfer reagent.

The yields of the compounds used in Table 1 are significant and no minor or partially alkylated products, e.g., guaiacol, were observed. The numbers correspond to isolated yields,

Example 2: Methylation of benzenedmh with dimethyl-carbonate and CS ₂ CO3 under micro wa ve conditions

Procedure: A solution of substrate (1.82 mmol; Table 2), CS2CG3 ( 1 equiv/OH), DMC (2 mL), and CHjCN ^' (2 ml), and mesitylene std. ( 100 μΤ) was heated in a 10 mL airtight glass vessel in an Anto Paar Monowave 300 microwave synthesis reactor at 1 0 °C with a stir rate of 600 rpm. The reaction products were analysed by GC-FID and GC-MS. The pressure of the reaction mixture increased from 0-1 1.4 bar over the course of 120 minutes. After 120 minutes, the reaction mixtures were cooled to room temperature, pressure released and the reaction mixture was analysed by GC-FID and GC-MS. Results are shown in Table 2.

Table 2

Entrv Substrate % yield Time {mm)

1 catechol 66.5 120

2 hydroquinoae 69.6 120

4-iaeifaylcaiechol 73.5 120

4 methyJhydroquinorte 90.3 1.20

5 resorcinoi 24.1 120

6 2,3-diineiliyihydroquinone 63.7 120

7 4-tthvlcatechoi 78.6 120 The yields of the compounds used in Table 2 are significant and no minor products, e.g., guaiacol, were observed. The numbers correspond to isolated yields.

Example 3: Methylation of other phenolic dials with dimethyl-carbonate and under m km wa ve conditions

Procedure: A solution of substrate (1.074 mmo ; Table 3), Csi Oj (1 ,074 mmol), DMC (2 ml ,), mesitylene std. (100 and CHsCN (5 mL) were heated in a 30 mL air tight glass vessel, in an Anton Paar Monowave 300 microwave synthesis reactor at 160 °C with a stir rate of 600 rpm. The pressure of the reaction mixture increased from 0-1 1 ,4 bar over the duration of 60/120 minutes. After 60/120 minutes, the reaction was cooled to room temperature, pressure released and the reaction mixture were analysed by GC-FID and GC- S. Results are shown in Table 3.

s % yield corresponds to to-meih iated product

Example 4: Methylation of 2,5-dihydroxybenzoic acid with dimethyl-carbonate and S2CO3 under microwave conditions

Procedure: A solution of 2,5-dihydroxybenzoic acid (1.074 mmol), CS ₂ CQ ₃ (1 .074 mmol), DMC (3 mL), mesitylene std. (100 ί), and C¾C (5 mL) were heated in a 30 mL air tight glass vessel in an Anton Paar Monowave 300 microwave synthesis reactor at 160 °C with a stir rate of 600 rpm. The pressure of the reaction mixture increased from 0-20 bar over the duration of 60 mimttes. After 60 minutes, the reaction was cooled to room temperatiire, pressure released and heated further to 180 and 240 minutes respectively, and the reaction mixtures were analysed by GC-FID and GC-MS. Results are shown in Table 4.

Table 4

Entry Substrate % yield ¾ yield Time

2,5 -dimethoxybenzoic acid 1. ,4-diraetliosybenzen.e (min)

1 2 ,5 -dibydioxybenzoic acid 30.7 13.0 180

2,5-dihydroxybenzoic acid 32.3 13.8 240 Example 5: Methylatwn of 1,3,5-benzenetr l with dimethylcarhonate and C¾G¾ under m icro wa ve conditions

Procedure: A solution of 1 ,3,5-trihydroxybenzene (1.074 mmol), CssCO (.1.074 ι ^η ιηοΐ), DMC ^' (2 ml), mesitylene std. (100 μί} ₃ and CHjC (5 niL) were heated in a 30 mL air tight glass vessel in an Anton Paar Monowave 300 microwave synthesis reactor at 160 °C with a stir rate of 600 rpro. The pressure of the reaction mixture increased from 0- 1 1.4 bar over the duratio of 120 minutes. After 120 minutes, the reaction was cooled to room temperature, pressure released and heated further 240 minutes respectively, and the reaction mixtures were analysed by GC-FID and GC-MS. Results are shown in Table 5.

* % yield corresponds to ^meth lated product

In. the experiments in Table 5, the starting to-hydroxy compound is not observed in the GC-FID results. This could be because the tri-rnethoxy product is the only compound formed or because the mono-methoxy-dihydroxy compound does not pass through the GC column.

Example 6: Methylation of a mixture of henzen ediols with dimethylcarbonate an d differen t base catalysts under microwave conditions

Procedure: A. 1 : 1 : 1 molar solution of catechol, hydroquinone and resorcinol (0.91 mmol each), base (2.73 mmol; Table 6), DMC (2 mL), mesitylene std. ( 100 pL). and C¾C (5 mL) were heated in a 30 mL air tight glass vessel in an Anton Paar Monowave 300 microwave synthesis reactor at 170 °C with a stir rate of 600 rpm. The pressure of the reaction mixture increased from 0-11.4 bar over the duration of 60/120 minutes. After 60/120 minutes, the reaction was cooled to room temperature, pressure released, and the reaction mixtures were analysed by GC-FID and GC-MS. Results, which show the average yield from two separate runs, are shown in Table 6.

* % yield 1,2-dtoiethoxybenzenc; % yield 1,4-dimethoxybenzenc; * % yield i,3-difiKll >xybenzene The results in Table 6 for DBU show that the yield of dialkylated product approximately correlates with the pKa of the starting benzenedioi, e.g., hyclroquinone (yield 80%; p a 10.35) > catechol (yield 78%; pKa 9.85) > resoreinol (yield 20%; pKa 9.8 i).

Example 7: Methylutimt of catechol with varying amounts of dimethylcarbonate under microwave conditions using DBU base catalyst

Procedure: A solution of catechol (0.91 mraol)., DBU (0.91 rnmol)., DMC (increased from; 2.96, 5.93, 8.90, 1 1.86, 23.73 rnmol corresponding to DMC/catechol ratio of 3.26, 6.52, 9.78, 13.0, 26.1 ; Table 7), mesitylene std. (100 \xL\ and CH ₃ CN (5 ml) were heated in a 30 mL air tight glass vessel, in an Anton Paar Monowave 300 microwave synthesis reactor at 170 °C with a stir rate of 600 rpm. The pressure of the reaction mixture increased from 0-11 bar over the duration of 20 minutes. After 20 minutes, the reaction was cooled to room temperature, pressure released, and the reaction mixtures were analysed by GC-FID and GC-MS. Results, which show the average yield from two separate runs, are shown in Table 7.

The data in Table 7 show that a DMCrcatchol ratio of 13 o above is advantageous for producing the Ms-methy lated product in yields of about 90% or greater.

Example 8: Consecutive cycles of methylatkm of catechol with dimethylcarbonate and DBU under microwave conditions

Procedure: A solution of catechol (0.91 rnmol), DBU (0.91 ramol), DMC (23,7 mmol) corresponding to a DMC/catechol ratio of 26, 1 , mesitylene (100 pJL), and CH ₃ CN (5 mL) were heated in a 30 mL air tight glass vessel in. an Anton Paar Monowave 300 microwave synthesis reactor at 370 °C with a stir rate of 600 rpin. The pressure of the reaction mixture increased from 0-1.2 bar over the duration of 20 minutes. After 20 min the reaction mixture was cooled to room temperature and an aliquote (approximately 50 μΐ) was taken, dissolved in diethyl ether and reaction products were analyzed by GC-FID and GC-MS. To the residual reaction mixture was added, a fresh batch of catechol (0.91 mmol), DMC (23.7 mmol), mesitylene (100 μΤ,) in C¾CN ( I niL) and the reactio run again under similar conditions as above and analysed for product formation. Results, which show the average conversion from two separate runs, are shown in Table 8,

* % conversion to i 2-dimethoxybenzene

Example 9: Consecutive cycles of meihylation of catechol with dimethylcarbon ate and

CsiCOj under microwave conditions

Procedure: A solution of catechol (0.91 mmol ), Cs ₂ C0 (0.91 mmol), DMC (23,7 mmol) corresponding to DMC/catechol ratio of 26.1 , mesitylene (100 μΐ,), and CH. N (5 raL) was heated in a 30 ml air tight glass vessel in an Anton Paar Monowave 300 microwave synthesis reactor at i 70 °C with a stir rate of 600 rpm. The pressure of the reaction mixture increased from 0-12 bar over the duration of 20 minutes. After 20 min the reaction mixture was cooled to room temperature and an aliquote (approximately 50 μ£ ) was taken, dissolved in diethyl ether and reaction products were analysed by GC-FID and GC-MS. To the residua! reaction mixture was added a fresh batch of substrate (0. 1 mmol), DMC (23.7 mmol), mesitylene (100 μΙ_) in C¾CN (1 ml) and the reaction run again under similar conditions as above and analysed for product formation. Results, which show the average conversion from two separate runs, are shown in Table 9. Table 9

Entrv Cycle % conversion ⁸

i i 80.1

2 2 81 .3

3 3 82.1.

4 4 82.3

5 5 84.1

6 6 84.1

84.4

8 8 84.1

9 9 85.

10 10 88.4

³ % conversion to ! ,2-dimelhoxybenzene

As shown in Table 9, cycling the O-alkylation process prevents unnecessary purification of the catalyst between reactions wi thout causing a loss in acti vity of the catalyst or a reduction in the yield of the > v~alkylated product.

Example JO: Methylation of catechol with dimethyicarbonate ami varying amounts of water under microwave conditions using DBU base catalyst

Procedure: A solution of catechol (0.91 mffioi), DBU (1.074 rjimo.1), DM.C (2 roL), mesitylene std. ( 100 μϋ,), distilled water (increasing such that ratio water/catechol is from 3, 6, and 12} and C¾CN (5 rnL) were heated i a 30 raL air tight glass vessel in an Anton Paar Monowave 300 microwave synthesis reactor at 160 or 370 °C with a stir rate of 600 rpm. The pressure of the reaction mixture increased from 0- 12 bar over the duration of 20/120 minutes. After 20/120 minutes, the reaction was cooled to room temperature, pressure released, and the reaction mixtures were analysed by GC-FID and GC-MS. Results, which show the average conversion from two separate runs, are shown in Table 10.

The results of Table 10 show that reaction mixtures having a water; catechol ratio of about .3: 1 produce the $-alky lated product with yields of greater than about 70%. Increasing the reaction time from 20 minutes to 120 minutes advantageously increases the yield to greater than about 80%, thereby indic atin g the certain concentrations of water may be tolerated at the expense of a lower yield.

Example 11: Methylation of catechol with dimethylcurbonate at various tempemtures under microwave conditions using Cs _? LOj base catalyst

General procedure: A solution of catechol (0.91 rnmol), CS2CO3 (1,074 mmol), DMC (2 mL), mesitylene std. (1.00 μ ,). and CH3CN (5 mL) were heated in a 30 mL air tight glass vessel in an Anton Paar Monowave 300 microwave synthesis reactor at temperature T °C (Table 1 1 ) with a stir rate of 600 rpm. The pressure of the reaction mixture increased from 0-15 bar over the duration of 20 minutes. After 20 minutes, the reaction was cooled to room temperature, pressure released, and the reaction mixtures were analysed by GC-FID and GC-MS. Results, which show the average conversion from two separate runs, are shown in Table .1 1.

The data in Table 1 1 show that a reaction temperature of at least 170 °C, or

advantageously a temperature of between about 170 °C and 200 °C produces yields of bis- aikylated products of greater than about. 88% and substantially no partially- alkylated products.

Example 12: Methylation of catechol with di ethylcarbonate under microwave conditions using CsjC(h base catalyst with various reaction stirring rates

Procedure: A solution of catechol (1.074 mmol ), CS2CO3 (1.074 mmol), DMC (2 mL), mesitylene std. ( 100 pL), and CHhCN (5 mL) were heated in a 30 mL air tight glass vessel in an Anton Paar Monowave 300 microwave synthesis reactor at 170 °C with stir rate r rpm. The pressure of the reaction mixture increased from 0-12 bar over the duration of 20 minutes. After 20 minutes, the reaction was cooled to room temperature, pressure released, and the reaction mixtures were analysed by GC-FID and GC-MS. Results, which show the average conversion from two separate runs, are shown in Table 12. Table 12

Entry Stir rate, r (rpm) % yield" Time (min)

1 300 83.8 20

600 89.3 20

3 900 87.4 20

4 1 100 90.2 20

* % yield of 1 ,2-dimetiioxybenzen.e

Data in Table 12 indicate that the yield of te-aikylated products may be less dependent on stirring rates than on other reactions conditions, but that stir rates of at least 300 rpm, or between about 300 and about 1 100 rpm, are suitable for use with the O-alkySation process of the invention.

Example J : Di lkykitkm of henzenedw!s in batch mode

Optimised batch conditions were performed according to Scheme 2 ^* .

0.325 mmo!, 0.13 M

Scheme 2

(MeC = acetomtrile; NMP = N-methyl-2-pyrrol.td.one)

Procedure: For reactions of catechol, the reaction solvent was MeCN (HFLC grade), and for reactions of resorcinol or hydroquinone, the reaction solvent was NMP (reagent grade). A 2-5 m ^' L Biotage microwave vial was charged with 2.5 mL of .reaction solution containing benzenediol (0.325 mmol, 0.13 M), DBU (1 equiv.}, DMC (25 equiv.) and oiesitylene standard (1 equiv.) in reaction solvent. The sealed reaction vial was then heated to 1.70 °C for 20 minutes using a Biotage Initiator microwave reactor. After reaction, the reaction vial was cooled to below room temperature by cooling to 40 °C with compressed nitro en, followed by submersion in an ice water bath. The reaction vial was then opened to the atmosphere and a sample was removed for analysis by GC-FID. Reaction conversion was determined by comparison against a standard calibration curve for the ratio of dialkylated product to mesitylene.

The measured conversions (GC-FID) are reported in Table 13, Table 13: Dialkylation ofbenzenediols in batch raode

Entry Starting Material Solvent Conversion (%) i Caiecbol MeCN 95

2 Sesorcinoi NMP 79

3 Hydroquinone NMP >97

The above results were translated to a flow reactor with conventional heating as shown in Figure 1 ,

Example 14: Procedure for dialkylation of benzenediols in flow mode

The eonttol software for the flow reactor was tised to report the concentration of the reaction mixture relative to steady state at the reactor outlet over time. For a 5.2 mmol scale reaction, the output is shown in Figure 2.

Procedure: For reactions of catechol, the reaction sol vent was MeCN (HPLC grade), and for reactions of resorcinol or hydroquinone, the reaction solvent was NMP (reagent grade).

This reaction was carried out in Vapourtec 2+/R4 Flow Reactor as shown i Figure 1. Pump A delivered a stock solution of benzenediol (5.2 mmol, 0.26 M), DMC (25 equiv.) and mesitylene standard (1 equiv.) in reaction solvent at 0.25 mL/min, and Pump B delivered a stock solution of DBU (5.2 mrnol, 0.26 M) in reaction solvent at 0.25 mL/min. The reaction mixture was collected at the reactor outlet and samples were analysed by GC-FID. Reaction con version was determined by comparison against a standard calibration curve for the ratio of dialkylated product to mesitylene.

GC-FID Analysis: GC-FID spectra were obtained with an Agilent Technologies 6850 GC mass spectrometer equipped with a HP- 1 column (methyl siloxane, 30 m 320 pm x 0.25 μιτί) and flame ionization detector. A 100 pL sample of the crude reaction mixture was diluted with 900 iiL MeCN for analysts. The temperature program was as set to: 50 °C for 2 minutes, then heating at 20 °C/min to 300 °C where the temperature was held for 5 minutes, injection was performed in split mode (ratio 125: 1) with an injector temperature of 300 °C. High-purity helium was used as carrier gas with a flow rate of 0.8 mL min. According to the data in Figure 2, the total reaction mixture exits the reactor between 20 and 120 minutes, and the material collected between approximately 35 and 100 minutes should reflect steady state perfomiance. Based on this prediction, samples were taken for analysis at 70 and 80 minutes as an indicator of steady state performance, and the total reaction mixture was collected from 20-130 minutes. Table 14 belo shows the conversion to dia!kylated product in each sample.

For all three reactions, the con version at steady state matches that of the overall reaction mixtur on 5,2 mmo.l scale. For the dialkylations of catechol and hydroquinone, the

performance of the Flow Reactor also closely matches that of the corresponding batch mode reactions (Table 13). However for the diaikylation of resorcinol, the conversion in flow mode (62%) is significantly lower than the conversion in batch mode (79%). It is possible to improve the conversions in both reaction modes by increasing the reaction temperature as shown in Table 15, below:

From the best of all the above observed conversions; A conversion of >90% for catechol and hydroquinone and 8 ^' 0% (under optimised conditions) for resorcinol would equate to an output of approximately 0.4-0.5 g of crude product per hour under continuous operation. Example 15: Large scale flaw mode procedures for dmlkylaihn ofbenzenedioh

It is envisaged that the methods described herein can be successfully applied in large scale flow procedures for the dialkylation of benzenediols.

For example, a Flow Synth system (flow microwave reactor) could be used for a continuous alkylation of dihydroxybenzenes on a larger scale. Potential/exemplary conditions and reaction volumes are shown in Table 16 and Table 17 below.

*fOr 500 mL reaction mixture.

The theoretical temperatures and reaction times (based on flow rate) above are based on the optimised conditions from the Vapoiutec Flow Reactor.

Conducting these or similar methods is expected to increase the gross output of alkylated products and increase the cost effectiveness of their production., as well as resulting in other practical processing efficiencies compared to static batch processes. Further, these methods may potentially lead to equal or greater yields and/or conversions of starting materials to fully alkylated products.