Synthesis of alkyl ARYL ethers

Abstract

The present disclosure provides for a method of producing an alkyl aryl ether. The method includes forming a reaction mixture of a) a conjugated base of phenol; b) a C3 to C8 alkyl chloride in a molar equivalent 1 to 10 relative to 1 molar equivalent of a); and c) a quaternary ammonium salt transfer catalyst of Formula I (I) where each of R1, R2, R3 and R4 is independently selected from a C2 to C6 alkyl, X is selected from the group consisting of Cl and Br, where c) is present in a mole equivalent of greater than 0.02 relative to 1 molar equivalent of a); and reacting the reaction mixture at a temperature in a range of 60 to 90°C for at least 1 hour to less than 100 hours to produce the alkyl aryl ether.

Description

[0001] SYNTHESIS OF ALKYL ARYL ETHERS Technical Field The present disclosure relates generally to the synthesis of alkyl aryl ethers. Background Alkyl aryl ethers are a class of organic compounds where an alkyl group (a straight or branched chain of carbon atoms with single bonds and attached hydrogen atoms) is bonded to an aryl group (an aromatic ring system, typically a benzene ring) through an ether linkage (an oxygen atom connecting the two groups). These compounds can be used for a number of different applications, including as solvents in various industries like paints, coatings, and pharmaceuticals due to their good solvating properties for a variety of materials; fragrances and flavors; pharmaceuticals; dyes and pigments; and as synthetic building blocks for more complex organic molecules. Of the various approaches to synthesizing alkyl aryl ethers, the use of alkyl chlorides is highly desirable due to its relatively low cost and high availability, but its use is known to be problematic. Specifically, the problem with known processes for synthesizing alkyl aryl ethers from alkyl chlorides are one of the following or a combination of them: low yield; low process throughput (product / time); use of expensive reactants and / or catalysts and the generation of waste. All these problems increase the cost of producing alkyl aryl ethers from alkyl chlorides and in particular butyl phenyl ether (BPE). The need in the art is, therefore, to help address the above identified problems in producing BPE so to help improve the economics of utilizing BPE in the marketplace. Summary The aforementioned needs are met by various aspects of the present disclosure. Embodiments of the present disclosure provide for a process that affords alkyl aryl ethers and in particular butyl phenyl ether (BPE). The process of the present disclosure helps to provide improvements in the production of alkyl aryl ethers, and especially affords the production of BPE in high yield (values of at least 90 % and higher) with high process throughput (e.g., reaction times of less than 10 hours). These and other advantages of the present disclosure are provided herein. As discussed herein, the synthesis of alkyl aryl ethers, such as BPE, can be undertaken by one of two primary methods according to the present disclosure. The first is through an azeotropic method and the second is through an anhydrous method. For the azeotropic method, the general procedure is to provide an aqueous solution of sodium phenate (also known as sodium phenoxide), where such an aqueous solution can be made, among other ways, by treating phenol with an aqueous solution of sodium hydroxide, as provided herein. The concentration of water present in the azeotropic method can, for example, be less than 10 weight percent, based on the total weight of the reaction mixture. For the various embodiments, the aqueous solution of sodium phenate is treated with an alkyl chloride, for example n-butyl chloride, to form a reaction mixture in which the alkyl chloride can act as both reactant and solvent for the reaction mixture. Tetrabutylammonium bromide (TBAB) is added as a solid and / or as an aqueous solution to the reaction mixture as a phase transfer catalyst. The reaction mixture is then heated from which an alkyl chloride / water (e.g., n-butyl chloride / water) azeotrope is removed (e.g., collected in a Dean-Stark apparatus) with alkyl chloride recycled back to the reactor to drive the reaction in producing a high yield of the alkyl aryl ether, as discussed herein. Alternatively, the anhydrous method treats anhydrous sodium phenate with an alkyl chloride, acting as both the solvent and reactant, in the presence of TBAB. This reaction mixture is stirred and heated, as discussed herein, to produce a high yield of the alkyl aryl ether. For both methods, the reaction times can be 100 hours or less and reaction components, such as the alkyl chloride, can be recycled to improve efficiencies, as discussed herein. Regarding the present disclosure, the method of producing an alkyl aryl ether can include forming a reaction mixture of a) a conjugated base of phenol; b) a C3 to C8 alkyl chloride in a molar equivalent 1 to 10 relative to 1 molar equivalent of a); and c) a quaternary ammonium salt transfer catalyst of Formula I: I where each of R1, R2, R3and R4is a C2 to C6 alkyl, X is selected from the group consisting of Cl and Br, and c) is present in a mole equivalent of greater than 0.02 relative to 1 molar equivalent of a); and reacting the reaction mixture at a temperature in a range of 60 to 90oC for at least 1 hour to less than 100 hours to produce the alkyl aryl ether. For the various embodiments, a) the conjugated base of phenol can be selected from the group of sodium phenate and potassium phenate. In one embodiment, a) the conjugated base of phenol is sodium phenate. In one embodiment, a) the conjugated base of phenol is sodium 4- methyl phenate. For the various embodiments, the C3 to C8 alkyl chloride can be selected from the group consisting of n-propyl chloride, n-butyl chloride, iso-butyl chloride, 1-chloropentane, iso-pentyl chloride, 1-chlorohexane, 1-chloroheptane, 1-chlorooctane and combinations thereof. For the various embodiments, the C3 to C8 alkyl chloride can be selected from the group consisting of n- butyl chloride, 1-chlorohexane, 1-chlorooctane and combinations thereof. For the various embodiments, for the quaternary ammonium salt phase transfer catalyst of Formula I each of R1, R2, R3and R4is independently selected from a C2 alkyl and a C4 alkyl. For the various embodiments, the quaternary ammonium salt phase transfer catalyst can be selected from the group consisting of tetrabutylammonium bromide (TBAB), tetrabutylammonium chloride, tetraethylammonium bromide (TEAB) and combinations thereof. For the various embodiments, the quaternary ammonium salt phase transfer catalyst can be tetrabutylammonium bromide (TBAB). For the various embodiments, the TBAB can be present in a mole equivalent of 0.026 to 0.10 relative to 1 molar equivalent of a). For the various embodiments, for b) the C3 to C8 alkyl chloride has a molar equivalent of 3 to 5 relative to 1 molar equivalent of a). In one embodiment, the reaction mixture consist essentially of a), b) and c). In an additional embodiment, a) is sodium phenate; b) is n-butyl chloride, c) is tetrabutylammonium bromide and the alkyl aryl ether is butyl phenyl ether (BPE). For the various embodiments, reacting the reaction mixture is done in an anhydrous state. In an alternative embodiment, the reaction mixture includes d) water in an amount less than 3 percent by weight based on the total weight of a), b), c) and d). Detailed Description Any reference to elements of the Periodic Table of Elements are those published by CRC Press, Inc., 1990-1991. Reference to a group of elements in this table is by the new notation for numbering groups. For purposes of United States patent practice, the contents of any referenced patent, patent application or publication are incorporated by reference in their entirety (or its equivalent U.S. version is so incorporated by reference) especially with respect to the disclosure of definitions (to the extent not inconsistent with any definitions specifically provided in this disclosure) and general knowledge in the art. The numerical ranges disclosed herein include all values from, and including, the lower and upper value. For ranges containing explicit values (e.g., 1 or 2, or 3 to 5, or 6, or 7), any subrange between any two explicit values is included (e.g., the range 1-7 above includes subranges of from 1 to 2; from 2 to 6; from 5 to 7; from 3 to 7; from 5 to 6; etc.). Unless stated to the contrary, implicit from the context, all parts and percents are based on weight and all test methods are current as of the filing date of this disclosure. The term "reaction mixture” and like terms mean a physical combination of two or more substances that undergo chemical change to produce products, where the reaction mixture can include pre-reaction, reaction, and post-reaction mixtures, the latter of which will include reaction products and by-products as well as unreacted components of the reaction mixture and decomposition products, if any, formed from the one or more components of the pre-reaction or reaction mixture. The terms "comprising," "including," "having" and their derivatives, are not intended to exclude the presence of any additional component, step or procedure, whether or not the same is specifically disclosed. In order to avoid any doubt, all compositions claimed through use of the term "comprising" may include any additional additive, adjuvant, or compound, unless stated to the contrary. In contrast, the term "consisting essentially of" excludes from the scope of any succeeding recitation any other component, step, or procedure, excepting those that are not essential to operability. The term "consisting of" excludes any component, step, or procedure not specifically delineated or listed. The term "or," unless stated otherwise, refers to the listed members individually as well as in any combination. Use of the singular includes use of the plural and vice versa. As used herein, the symbol “~” means about. The entire contents of the Summary section is incorporated in the present Detailed Description by reference. As discussed herein, embodiments of the present disclosure provide for a method of producing alkyl aryl ethers, in particular butyl phenyl ether (BPE), in high yields (values of at least 90 % and higher) with high process throughput (e.g., reaction times of less than 100 hours). The advantages of the present disclosure are provided, at least in part, through the use of a particular phase transfer catalyst, along with a specific conjugated base of phenol and alkyl chloride(s) in the reaction mixture. Regarding the present disclosure, the method of producing an alkyl aryl ether can include forming a reaction mixture of a) a conjugated base of phenol; b) a C3 to C8 alkyl chloride in a molar equivalent 1 to 10 relative to 1 molar equivalent of a); and c) a quaternary ammonium salt transfer catalyst of Formula I: I where each of R1, R2, R3and R4is independently selected from a C2 to C6 alkyl, X is selected from the group consisting of Cl and Br, and c) is present in a mole equivalent of greater than 0.02 relative to 1 molar equivalent of a); and reacting the reaction mixture at a temperature in a range of 60 to 90oC for at least 1 hour to less than 100 hours to produce the alkyl aryl ether. a) Conjugated Base of Phenol For the various embodiments, a) the conjugated base of phenol can be selected from the group of sodium phenate and potassium phenate. In one embodiment, a) the conjugated base of phenol is sodium phenate. In one embodiment, a) the conjugated base of phenol is sodium 4- methyl phenate. Other examples of possible conjugated bases of phenol can include, but are not limited to, potassium 4-methyl phenate, and lithium phenate, calcium phenate and / or magnesium phenate, where the phenol moiety can be substituted with at least one alkyl group (e.g., methyl group). For example, the conjugated base of phenol can have the structure of Formula II: II where Z can be lithium, sodium, pot ereof; Y is an alkyl group containing 1 - 6 carbon atoms, preferably 1 - 2 carbon atoms; an alkoxy group containing 1 - 6 carbon atoms, preferably 1 carbon atom; an alkyl ether group containing 2 - 6 carbon atoms, preferably 2 - 4 carbon atoms; cyclohexyl; ketone; or nitrile. The alkyl, alkoxy, or alkyl ether group may be branched or unbranched. The n group can have a value of 0 - 3 and two Y groups may be taken together to form a ring, i.e., resulting in naphthyl. b) C3 to C8 Alkyl Chloride For the various embodiments, b) the C3 to C8 alkyl chloride can be straight chain alkyl chlorides, where the chlorine is attached to a primary carbon of the alkyl chain. For the various embodiments, the C3 to C8 alkyl chloride can be selected from the group consisting of n-propyl chloride, n-butyl chloride, iso-butyl chloride, 1-chloropentane, iso-pentyl chloride, 1- chlorohexane, 1-chloroheptane, 1-chlorooctane and combinations thereof. For the various embodiments, the C3 to C8 alkyl chloride can be selected from the group consisting of n-butyl chloride, 1-chlorohexane, 1-chlorooctane and combinations thereof. Preferably, the C3 to C8 alkyl chloride is n-butyl chloride. For the various embodiments, the use of n-butyl chloride as the solvent and reactant helps to avoid both low yields and long process times, as illustrated in the Examples section herein. In an additional embodiment, the alkyl chloride can be a branched alkyl, where again the chlorine is attached to the primary, or terminal, carbon that also includes two hydrogens and the branch(es) extend from one or more carbons of the carbon chain extending from the primary carbon. Examples of such alkyl chlorides include, but are not limited to, 1-chloro-3- methylpentane, 1-chloro-3-ethylpentane, 1-chloro-2-methylpropane, 1-chloro-2,2- dimethylpropane, 1-chloro-2-methylbutane, 1-chloro-2-ethylpropane, and 1-chloro-4- ethyloctane, among others. For the various embodiments, b) the C3 to C8 alkyl chloride is present in the reaction mixture in a molar equivalent 1 to 10 relative to 1 molar equivalent of a). For the various embodiments, the molar equivalent for b) relative to 1 molar equivalent of a) in the reaction mixture can be from a lower value of 1, or 1.5, or 2, or 2.5, or 3 to an upper value of 3.5, or 4, or 4.5 or 5, or 5.5, or 6, where any combination of a lower value and an upper value is possible. For example, for b) the C3 to C8 alkyl chloride can have a molar equivalent of 3 to 10 relative to 1 molar equivalent of a). In an additional embodiment, for b) the C3 to C8 alkyl chloride can have a molar equivalent of 3 to 6 relative to 1 molar equivalent of a). In a further embodiment, for b) the C3 to C8 alkyl chloride can have a molar equivalent of 3 to 5 relative to 1 molar equivalent of a). c) Quaternary Ammonium Salt Phase Transfer Catalyst For the various embodiments, c) the quaternary ammonium salt phase transfer catalyst has the structure of Formula I: I where each of R1, R2, R3and R4is independently selected from a C2 to C6 alkyl and X is selected from the group consisting of Cl and Br. For the various embodiments, each of R1, R2, R3and R4is preferably a straight chain alkyl. For the various embodiments, each of R1, R2, R3and R4is preferably independently selected from a C2 alkyl and a C4 alkyl. In specific examples, for the various embodiments the quaternary ammonium salt phase transfer catalyst can be selected from the group consisting of tetrabutylammonium bromide (TBAB), tetrabutylammonium chloride (TBAC), tetraethylammonium bromide (TEAB) and combinations thereof. Preferably, the quaternary ammonium salt phase transfer catalyst is TBAB. The use of TBAB, as provided herein, helps to avoid both long process times and low yield of the alkyl aryl ether. For the various embodiments, c) is present in a mole equivalent of greater than 0.02 relative to 1 molar equivalent of a). For the various embodiments, the molar equivalent for c) relative to 1 molar equivalent of a) in the reaction mixture can be from a lower value of greater than 0.02, or 0.04, or 0.05, or 0.08, or 0.1 to an upper value of 0.3, or 0.5, or 0.7 or 0.9, or 1, where any combination of a lower value and an upper value is possible. For example, c) can have a molar equivalent of greater than 0.02 to 0.7 relative to 1 molar equivalent of a). In an additional embodiment, c) can have a molar equivalent of greater than 0.02 to 0.5 relative to 1 molar equivalent of a). In an additional embodiment, c) can have a molar equivalent of greater than 0.02 to 0.3 relative to 1 molar equivalent of a). For the various embodiments, the TBAB can preferably be present in a mole equivalent of 0.026 to 0.10 relative to 1 molar equivalent of a). For the various embodiments, the reaction mixture consists essentially of a), b) and c), where a), b) and c) are as provided herein. For example, the reaction mixture can be such that a) is sodium phenate; b) is n-butyl chloride, c) is tetrabutylammonium bromide and the alkyl aryl ether is butyl phenyl ether (BPE). In one embodiment, the reaction mixture consists essentially of a) sodium phenate; b) n-butyl chloride, c) tetrabutylammonium bromide and the alkyl aryl ether is butyl phenyl ether (BPE). For the various embodiments, reacting the reaction mixture is done in an anhydrous state, as discussed herein. In alternative embodiments, the reaction mixture of a), b) and c) can include additional components. Examples of such additional components can include water, as discussed herein. For example, in an alternative embodiment, the reaction mixture includes d) water in an amount less than 10 percent by weight (wt.%) based on the total weight of a), b), c) and d). Preferably, when d) water is present in the reaction mixture it is in an amount less than 3 wt.% based on the total weight of a), b), c) and d). In other words, the reaction mixture can include d) water in an amount less than 3 wt.% based on the total weight of a), b), c) and d). In an additional preferred embodiment, when d) water is present in the reaction mixture it is in an amount less than 1.5 wt.% based on the total weight of a), b), c) and d). For the various embodiments, the d) water present in the reaction mixture can be achieved by starting with anhydrous sodium phenate. For the various embodiments, the d) water concentration in the reaction mixture can be achieved by azeotropic water removal, as discussed herein. For the various embodiments, reacting the reaction mixture is done at a temperature in a range of 60 to 90oC for at least 1 hour to less than 100 hours to produce the alkyl aryl ether. Preferably, reacting the reaction mixture is done at a temperature in a range of 70 to 90oC or in a range of 75 to 85oC. Specific preferred reaction temperatures for reacting the reaction mixture include 75oC, 78oC or 85oC. For the various embodiments, reacting the reaction mixture is done for at least 1 hour to less than 50 hours, or for at least 1 hour to less than 15 hours to produce the alkyl aryl ether. Preferably, reacting the reaction mixture is done for at least 1 hour to less than 12 hours. In an additional preferred embodiment, reacting the reaction mixture is done for at least 4 hours to less than 12 hours. As discussed herein, the synthesis of alkyl aryl ethers, such as BPE, can be undertaken by one of two primary methods according to the present disclosure. The first is through an azeotropic method and the second is through an anhydrous method. For the azeotropic method, the general procedure is to provide an aqueous solution of a) the conjugated base of phenol, as provided herein, where such an aqueous solution can be made, among other ways, by treating phenol with an aqueous solution of sodium hydroxide, in the case of sodium phenate, or potassium hydroxide, in the case of potassium phenate. The concentration of water present in the azeotropic method can, for example, be less than 10 weight percent, based on the total weight of the reaction mixture, as provided herein. For the various embodiments, the aqueous solution of the conjugated base of phenol (e.g., an aqueous solution of sodium phenate) can be treated with the C3 to C8 alkyl chloride, for example n-butyl chloride, to form a reaction mixture, as discussed herein, in which the C3 to C8 alkyl chloride can act as both reactant and solvent for the reaction mixture. The quaternary ammonium salt phase transfer catalyst (e.g., TBAB) is added as a solid and / or as an aqueous solution to the reaction mixture as the phase transfer catalyst. The reaction mixture is then heated, as discussed herein, from which an alkyl chloride / water (e.g., n-butyl chloride / water) azeotrope is removed (e.g., collected in a Dean-Stark apparatus) to drive the reaction in producing a high yield of the alkyl aryl ether, as discussed herein. For the various embodiments, the C3 to C8 alkyl chloride can be recycled back to the reactor to help improve the efficiencies for the reaction. For the given reaction times provided herein, yields of 90 % and greater can be achieved for the alkyl aryl ether. The resulting products can be cooled, and the solids removed by water washes or filtration to afford a mixture that includes both the C3 to C8 alkyl chloride (e.g., n-butyl chloride) and the alkyl aryl ether (e.g., BPE). The alkyl aryl ether can then be separated from the C3 to C8 alkyl chloride and other components in the mixture by known separation techniques, such as, for example, through fractional distillation (e.g., low boiling n-butyl chloride can be removed from the mixture under reduced pressure, where it can be recycled back to the reaction mixture). Alternatively, the anhydrous method treats an anhydrous conjugated base of phenol (e.g., anhydrous sodium phenate) with the C3 to C8 alkyl chloride, for example n-butyl chloride, acting as both the solvent and reactant, in the presence of the quaternary ammonium salt phase transfer catalyst (e.g., TBAB) to form the reaction mixture. The reaction mixture is stirred and heated, as discussed herein, to produce a high yield of the alkyl aryl ether. For both methods, the reaction times can be as provided herein and the reaction components, such as the C3 to C8 alkyl chloride, can be recycled during the process to improve efficiencies, as discussed herein. By way of example, and not limitation, some embodiments of the present disclosure are described in detail in the following examples. Examples Amounts provided for the Inventive Examples (IE) and Comparative Examples (CE) are in parts per hundred unless otherwise noted. Materials Phenol [99+%], butyl phenyl ether (BPE) [99%], tetrabutylammonium bromide (TBAB) [99%], n-butyl chloride [99.5%] and NaOH [98+%] were all purchased from Sigma Aldrich. Anhydrous sodium phenate (NaOPh) [98%] was purchased from Fisher Scientific or synthesized as described below. Toluene [99.8%] was purchased from Acros Organics. All materials were used as received without further purification unless otherwise described herein. Prior to reaction, phenol was melted at 65 °C in the oven overnight and transferred to the reactor by pipette A 50% NaOH solution was made with deionized water. GC-MS Method Gas chromatography–mass spectrometry (GC-MS) of the IE and CE herein was conducted on the following device using the method summarized in Table 1. Table 1. GC-MS parameters. Instrument Agilent 6890 GC system with Agilent 5975C C) Mode Constant flow Average velocity 29 cm / sec Inventive Example (IE) 1 Azeotropic Removal of Water: Preparation of Butyl Phenyl Ether (BPE) The synthesis of BPE was demonstrated in high yield from phenol, NaOH (aq.), tetrabutylammonium bromide (TBAB), and n-butyl chloride with in situ azeotropic water stripping. The process vessel was a 500 mL four-necked round bottomed flask. The vessel was fitted with an overhead stirrer, a Dean-Stark apparatus, temperature probe, and inert gas adaptor. The water was removed with a Dean-Stark apparatus connected to a high efficiency condenser cooled with water (2 to 4 °C). During the process the water / n-butyl chloride azeotrope condensed, and the water separated, while the n-butyl chloride was recycled back to the reactor. The reaction vessel was charged with a solution composed of phenol 32.50 g (0.34533 mol or approximately 1.0 mol equiv.) and water 12.73 g (0.70662 mole or approximately 2.0 mol equiv.), followed by the addition of NaOH (27.63 g; 50 wt.% aqueous solution; 0.354 mole or approximately 1 mol equiv.). The mixture was stirred at 200 rpm and the temperature increased to 64 °C and allowed to cool to 35 °C after 30 minutes. TBAB (11.13 g; 50 wt.% aqueous solution (0.017263 mole) was added to the vessel, corresponding to a 0.05 molar equivalent of TBAB to phenol. The vessel was charged with n-butyl chloride (143.86 g) and the mixture was heated at 78 °C. The reaction mixture was heated for a total time of 11.5 hours and 36.01 grams of water was collected, which corresponds to a calculated recovery of 94%. The mixture cooled to room temperature (23 °C) and water (143 g) was added, which completely dissolved all the solid salts. The organic layer was then separated from the aqueous layer using a separatory funnel and purified by rotary evaporator (20 mbar; 40 °C; 30 min). The process afforded BPE (47.65g; 92% yield) measured using GC-MS as provided herein. IE 1 demonstrated the feasibility of BPE synthesis at high yield starting from phenol with in situ azeotropic water stripping. IE 2 Anhydrous reaction: Preparation of BPE A 500 mL four-necked round bottomed flask was used as the process vessel. The vessel was fitted with an overhead stirrer, a reflux condenser, temperature probe, and inert gas adaptor. Prior to starting the process, the reactor was flushed with N2 gas at 5 mL / min overnight. The vessel was charged with 40.00 g (1 mol equiv.) of sodium phenate, 143.53 g (4.5 mol equiv.) of n-butyl chloride, and 5.55 g (0.05 mol equiv.) of TBAB. The mixture was stirred at 200 rpm and heated for 7 hours at 75 °C. The mixture cooled to room temperature and the solids were removed by filtration, followed by rotary evaporation to isolate BPE (50.55 g; 98%, relative to sodium phenate) and n-butyl chloride solvent. The isolated n-butyl chloride has a purity of 99.4 wt.%, (GC-MS) and can be recycled as a reactant / solvent. IE 3 1.500 g (1 mol equiv.) of sodium phenate, 5.382 g (4.5 mol equiv.) of n-butyl chloride, and 0.417 g of (0.10 mol equiv.) tetraethylammoniumbromide (TEAB) were added to a 40 mL glass reactor. The reaction mixture was heated with mixing at 75 °C for 7 hours. After reaction, ~1 g of sample was taken from the reaction vial using a syringe, filtered into a GC vial, and analyzed by GC-MS. Yield to BPE was measured to be 100%. Comparative Example (CE) A Similar to IE 2, BPE synthesis from n-butyl chloride and sodium phenate was performed at a lower TBAB loading with n-butyl chloride as the solvent. In CE A, 3 g (1 mol equiv.) of sodium phenate, 8.373 g (3.5 mol equiv.) of n-butyl chloride, and 0.167 g (0.02 mol equiv.) of TBAB were added to a 40 mL glass reactor. The reaction mixture was heated with mixing at 75 °C for 7 hours. It was then filtered under reduced pressure to remove solids, followed by rotary evaporation to collect 1.998 g of BPE at an isolated yield of 51.5% with respect to sodium phenate. Observations from CE A suggest that a TBAB loading needs to have specific values for improved efficiencies. CE B Toluene was explored as the solvent. In a similar example to IE 2, a 40 ml glass reactor was charged with 2.91 g (1 mol equiv.) of sodium phenate, 2.32 g (1 mol equiv.) of n-butyl chloride, 11.55 g (5 mol equiv.) of toluene, and 0.403 g (0.05 mol equiv.) of TBAB. The reaction mixture was heated with mixing at 85 °C. The BPE yield was analyzed by GC-MS, as provided herein, and found to be 18.0 and 78.2% at 4 and 24 hours, respectively. A lower BPE yield was observed with toluene solvent; n-butyl chloride is favored over toluene as a solvent. CE C Ethanol was explored as a solvent. 3 g (1 mol equiv.) of sodium phenate, 2.392 g (1 mol equiv.) of n-butyl chloride, and 4.762 g (4 mol equiv.) of ethanol were added to a 40 mL glass reactor. TBAB was not used in CE C. The reaction mixture was heated with mixing at 75 °C for 7 hours. After reaction, the mixture was first filtered by vacuum filtration to remove solids and washed by 1 volume equivalent of water. The organic layer was separated by rotary evaporation to collect 0.908 g of BPE at an isolated yield of 23.4% with respect to sodium phenate. CE D In a similar example using ethanol as solvent, 3.059 g (1 mol equiv.) of sodium phenate, 2.312 g (1 mol equiv.) of n-butyl chloride, and 5.772 g (5 mol equiv.) of ethanol were added to a 40 mL glass reactor. TBAB was not used in CE D. The reaction mixture was heated with mixing at 75 °C. Reaction yield to BPE was analyzed by GC-MS as provided herein to be 25.7 and 68.5% at 4 and 24 hours, respectively. Both CE B, C and D showed that the use of n-butyl chloride as solvent is favored over the use of toluene or ethanol as solvent to achieve yield above 90% at 7 h.

[0002] CE E In another similar example using ethanol as the solvent but instead using n-butyl bromide as the reactant, 3.059 g (1 mol equiv.) of sodium phenate, 3.431 g (1 mol equiv.) of n-butyl bromide, and 5.772 g (5 mol equiv.) of ethanol were added to a 40 mL glass reactor. TBAB was not used in CE E. The reaction mixture was heated with mixing at 75 °C. Reaction yield to BPE was analyzed by GC-MS, as provided herein, to be 90.6 and 94.3% at 4 and 24 hours, respectively. n-Butyl bromide is significantly more reactive compared with n-butyl chloride. However, the price of n-butyl bromide is almost twice that of n-butyl chloride and disposing of Br containing waste is often more difficult and expensive. The use of butyl chloride as a reactant is still preferred for BPE synthesis. CE F 2.5 g (1 mol equiv.) of phenol, 2.614g (1.23 mol equiv.) of 50 wt.% NaOH aqueous solution, 3.572 g (7.47 mol equiv.) of deionized water, 0.548 g (0.032 mol equiv.) of 50 wt.% TBAB aqueous solution, and 6.658 g (2.72 mol equiv.) of toluene was added to a 40 mL glass reactor. The mixture was heated to 60 °C under stirring for 1 h. After 1 h, 2.436 g (1 mol equiv.) of n-butyl chloride was added to the reactor. The reaction mixture was heated with mixing at 75 °C for 4.5 h. Reaction yield to BPE was analyzed by GC-MS, as provided herein, to be 2% at 4.5 hours. Comparatively, IE 2 was performed in the absence of water. The presence of water significantly reduced yield. Removal of water is necessary and feasible to achieve yield above 90% at 7h as demonstrated by IE 2. Quaternary Ammonium Salt Catalysts IE 4 3 g (1 mol equiv.) of sodium phenate, 10.765 g (4.5 mol equiv.) of n-butyl chloride, and 0.272 g of (0.05 mol equiv.) tetraethyl ammonium bromide (TEAB) were added to a 40 mL glass reactor. The reaction mixture was heated with mixing at 75 °C for 7 hours. After reaction, ~1 g of sample was taken from the reaction vial using a syringe, filtered into a GC vial, and analyzed by GC-MS, as provided herein. Yield to BPE was measured to be 85% using GC-MS, as provided herein. CE G 3 g (1 mol equiv.) of sodium phenate, 10.765 g (4.5 mol equiv.) of n-butyl chloride, and 0.522 g (0.05 mol equiv.) of Aliquat 336 were added to a 40 mL glass reactor. The reaction mixture was heated with mixing at 75 °C for 7 hours. After reaction, ~1 g of sample was taken from the reaction vial using a syringe, filtered into a GC vial, and analyzed by GC-MS, as provided herein. Yield to BPE was measured to be 5% using GC-MS, as provided herein. Catalyst Loading and Solvent Loading IE 5 3.0 g (1 mol equiv.) of sodium phenate, 14.353 g (6 mol equiv.) of n-butyl chloride, and 0.8330 g (0.10 mol equiv.) of TBAB were added to a 40 mL glass reactor. The reaction mixture was heated with mixing at 75 °C for 4 hours. After reaction, ~1 g of sample was taken from the reaction vial using a syringe, filtered into a GC vial, and analyzed by GC-MS. Yield to BPE was measured to be 90% measured using GC-MS, as provided herein. IE 6 1.5 g (1 mol equiv.) of sodium phenate, 3.588 g (3 mol equiv.) of n-butyl chloride, and 0.108 g (0.026 mol equiv.) of TBAB were added to a 40 mL glass reactor. The reaction mixture was heated with mixing at 75 °C for 7 hours. After reaction, ~1 g of sample was taken from the reaction vial using a syringe, filtered into a GC vial, and analyzed by GC-MS. Yield to BPE was measured to be 74% measured using GC-MS, as provided herein. IE 7 1.5 g (1 mol equiv.) of sodium phenate, 4.749 g (3.97 mol equiv.) of n-butyl chloride, and 0.200 g (0.048 mol equiv.) of TBAB were added to a 40 mL glass reactor. The reaction mixture was heated with mixing at 75 °C for 7 hours. After reaction, ~1 g of sample was taken from the reaction vial using a syringe, filtered into a GC vial, and analyzed by GC-MS. Yield to BPE was measured to be 96% using GC-MS, as provided herein. IE 8 1.5 g (1 mol equiv.) of sodium phenate, 3.588 g (3 mol equiv.) of n-butyl chloride, and 0.250 g (0.060 mol equiv.) of TBAB were added to a 40 mL glass reactor. The reaction mixture was heated with mixing at 75 °C for 7 hours. After reaction, ~1 g of sample was taken from the reaction vial using a syringe, filtered into a GC vial, and analyzed by GC-MS. Yield to BPE was measured to be 98% using GC-MS, as provided herein. IE 9 1.5 g (1 mol equiv.) of sodium phenate, 4.892 g (4.09 mol equiv.) of n-butyl chloride, and 0.092 g (0.022 mol equiv.) of TBAB were added to a 40 mL glass reactor. The reaction mixture was heated with mixing at 75 °C for 7 hours. After reaction, ~1 of sample was taken from the reaction vial using a syringe, filtered into a GC vial, and analyzed by GC-MS. Yield to BPE was measured to be 48% using GC-MS, as provided herein. CE H 1.5 g (1 mol equiv.) of sodium phenate, 5.980 g (5 mol equiv.) of n-butyl chloride, and 0.042 g (0.010 mol equiv.) of TBAB were added to a 40 mL glass reactor. The reaction mixture was heated with mixing at 75 °C for 7 hours. After reaction, ~1 g of sample was taken from the reaction vial using a syringe, filtered into a GC vial, and analyzed by GC-MS. Yield to BPE was measured to be 34% using GC-MS, as provided herein. 2-Methyl Phenol / 4-Methyl Phenol CE I 1.850 g of sodium hydroxide was added to a mixture of 1.387 g of water and 7.860 g of methanol. The mixture was stirred at 500 rpm for 2 h until fully dissolved. 5.000 g of 2-methyl phenol was first dissolved in 4.5330 g of methanol. The sodium hydroxide solution was added dropwise to the 2-methyl phenol methanol solution and stirred at 500 rpm at room temperature for 3 h. The solvents were removed by rotary evaporation at 20 mbar and 80 ℃ for 30 min. The resulting solid was collected and was assumed to be sodium 2-methyl phenate. 1.694 g (1 mol equiv.) of sodium 2-methylphenate, 5.382 g (4.5 mol equiv.) of n-butyl chloride, and 0.208 g (0.050 mol equiv.) of TBAB were added to a 40 mL glass reactor. The reaction mixture was heated with mixing at 75 °C. After 7 hours , ~1 g of sample was removed from the reaction vial using a syringe, filtered into a GC vial, and analyzed by GC-MS. The measured methyl substituted BPE yield was 19% using GC-MS, as provided herein. IE 10 1.850 g of sodium hydroxide was added to a mixture of 1.387 g of water and 7.860 g of methanol. The mixture was stirred at 500 rpm for 2 h until fully dissolved. 5.000 g of 4-methyl phenol was first dissolved in 4.533 g of methanol. The sodium hydroxide solution was added dropwise to the 4-methyl phenol methanol solution and stirred at 500 rpm at room temperature for 3 h. The solvents were removed by rotary evaporation at 20 mbar and 80 ℃ for 30 min. The resulting solid was collected and was assumed to be sodium 4-methyl phenate. 1.694 g (1 mol equiv.) of sodium 4-methylphenate, 5.382 g (4.5 mol equiv.) of n-butyl chloride, and 0.208 g (0.050 mol equiv.) of TBAB were added to a 40 mL glass reactor. The reaction mixture was heated with mixing at 75 °C. After 7 hours , ~1 g of sample was removed from the reaction vial using a syringe, filtered into a GC vial, and analyzed by GC-MS. The methyl substituted BPE yield was measured to be 90% using GC-MS, as provided herein. Chlorohexane / Chlorodecane IE 11 1.500 g (1 mol equiv.) of sodium phenate, 7.013 g (4.5 mol equiv.) of n-hexyl chloride, and 0.208 g (0.050 mol equiv.) of TBAB were added to a 40 mL glass reactor. The reaction mixture was heated with mixing at 85 °C. After 7 hours, ~1 g of sample was removed from the reaction vial using a syringe, filtered into a GC vial, and analyzed by GC-MS. The hexylphenylether (HPE) yield was measured to be 87% using GC-MS, as provided herein. CE J 1.500 g (1 mol equiv.) of sodium phenate, 10.274 g (4.5 mol equiv.) of n-decyl chloride, and 0.208 g (0.050 mol equiv.) of TBAB were added to a 40 mL glass reactor. The reaction mixture was heated with mixing at 85 °C. After 7 hours, ~1 g of sample was removed from the reaction vial using a syringe, filtered into a GC vial, and analyzed by GC-MS. The BPE yield was measured to be 33% using GC-MS, as provided herein. n-Butyl Bromide CE K Phenol (50.00 grams, 0.531 mole) was added to a three neck, one liter, round bottom, glass reactor equipped with a chilled condenser (-2 °C), thermocouple - temperature controller - heating mantle assembly, overhead nitrogen inlet (0.2 LPM), and mechanical stirring consisting of a poly(tetrafluoroethylene) bearing seated in a glass fitting, paddle, and a glass shaft. A Dean Stark trap was interspersed between the reactor and condenser. Toluene (320.0 grams) was added and stirring commenced providing a solution. A solution of sodium hydroxide (24.4 grams, 0.61 mole) was added to the stirred solution over 2 minutes causing the temperature to increase from 20.1 °C to 40.5 °C, which was concurrent with formation of an easily stirred white slurry. One minute later, heating commenced causing rapid distillation of toluene and water azeotrope into the Dean Stark trap. After 2 hours, a maximum temperature of 110.2 °C was achieved with removal of 32.4 milliliters (33.68 grams) of aqueous phase as the bottom layer in the Dean Stark trap. The Dean Stark trap was removed and the condenser fitted directly to the reactor. TBAB (0.850 gram, 2.637 millimole) was added to the 21.6 °C slurry of sodium phenate in toluene, immediately followed by addition of n-butyl bromide (80.17 grams, 0.585 mole). Heating to 85 °C commenced over 14 minutes. After 3 hours 55 minutes at 85 °C, heating ceased and the product slurry was cooled to room temperature then vacuum filtered over a medium fritted glass funnel. Fresh toluene (50.0 grams) was used to wash product from the reactor interior and the powder collected on the fritted glass funnel. The colorless filtrate (391.84 grams) was transferred to a separatory funnel and sequentially washed 4 times with 39.18 gram portions of deionized water. Recovery of water from the washing was 99.1 %. Rotary evaporation at 25 °C of the washed product was completed to a final vacuum of 0.75 mm Hg. The transparent product (74.04 grams, 0.493 mole) was recovered in 92.82 % isolated yield (uncorrected) based on phenol. Area percent gas chromatographic analysis revealed a purity of 99.86 % n-butylphenyl ether with non-detectable phenol and n-butyl bromide and with minor residual toluene (0.012 area %). Cation IE 12 1.708 g (1 mol equiv.) of potassium phenate, 5.382 g (4.5 mol equiv.) of n-butyl chloride, and 0.208 g (0.050 mol equiv.) of TBAB were added to a 40 mL glass reactor. The reaction mixture was heated with mixing at 85 °C. After 7 hours, ~1 g of sample was taken from the reaction vial using a syringe, filtered into a GC vial, and analyzed by GC-MS. The BPE yield was measured to be 41% using GC-MS, as provided herein. Catalyst Loading IE 13 1.500 g (1 mol equiv.) of sodium phenate, 4.054 g (3.4 mol equiv.) of n-butyl chloride, and 0.117 g (0.028 mol equiv.) of TBAB were added to a 40 mL glass reactor. The reaction mixture was heated with mixing at 85 °C for 7 hours. After reaction, ~1 g of sample was taken from the reaction vial using a syringe, filtered into a GC vial, and analyzed by GC-MS. Yield to BPE was measured to be 58% using GC-MS, as provided herein. Water Level CE L 1.500 g (1 mol equiv.) of sodium phenate, 5.382 g (4.5 mol equiv.) of n-butyl chloride, 0.208 g (0.050 mol equiv.) of TBAB, and 0.205 g (0.030 weight percentage) of water were added to a 40 mL glass reactor. The reaction mixture was heated with mixing at 85 °C for 7 hours. After reaction, ~1 g of sample was taken from the reaction vial using a syringe, filtered into a GC vial, and analyzed by GC-MS. Yield to BPE was measured to be 17% using GC-MS, as provided herein.

Claims

What is Claimed is:

1. A method of producing an alkyl aryl ether comprising: forming a reaction mixture of: a) a conjugated base of phenol; b) a C3 to C8 alkyl chloride in a molar equivalent 1 to 10 relative to 1 molar equivalent of a); and c) a quaternary ammonium salt transfer catalyst of Formula I: I wherein each of R1, R2, R3and R4is independently selected from a C2 to C6 alkyl, X is selected from the group consisting of Cl and Br, and c) is present in a mole equivalent of greater than 0.02 relative to 1 molar equivalent of a); and reacting the reaction mixture at a temperature in a range of 60 to 90oC for at least 1 hour to less than 100 hours to produce the alkyl aryl ether.

2. The method of claim 1, wherein a) the conjugated base of phenol is selected from the group of sodium phenate and potassium phenate.

3. The method of claim 1, wherein a) the conjugated base of phenol is sodium phenate.

4. The method of claim 1, wherein a) the conjugated base of phenol is sodium 4-methyl phenate.

5. The method of any one of claims 1-4, wherein the C3 to C8 alkyl chloride is selected from the group consisting of n-propyl chloride, n-butyl chloride, iso-butyl chloride, 1-chloropentane, iso-pentyl chloride, 1-chlorohexane, 1-chloroheptane, 1-chlorooctane and combinations thereof.

6. The method of any one of claims 1-4, wherein the C3 to C8 alkyl chloride is selected from the group consisting of n-butyl chloride, 1-chlorohexane, 1-chlorooctane and combinations thereof.

7. The method of any one of claims 1-6, wherein for the quaternary ammonium salt transfer catalyst of Formula I each of R1, R2, R3and R4is independently selected from a C2 alkyl and a C4 alkyl.

8. The method of any one of claims 1-7, wherein the quaternary ammonium salt transfer catalyst is selected from the group consisting of tetrabutylammonium bromide (TBAB), tetrabutylammonium chloride (TBAC), tetraethylammonium bromide (TEAB) and combinations thereof.

9. The method of any one of claims 1-8, wherein the quaternary ammonium salt transfer catalyst is tetrabutylammonium bromide (TBAB).

10. The method of claim 9, wherein the TBAB is in a mole equivalent of 0.026 to 0.10 relative to 1 molar equivalent of a).

11. The method of any one of claims 1-10, wherein for b) the C3 to C8 alkyl chloride has a molar equivalent of 3 to 10 relative to 1 molar equivalent of a).

12. The method of any one of claims 1-11, wherein the reaction mixture consists essentially of a), b) and c).

13. The method of claim 1, wherein a) is sodium phenate; b) is n-butyl chloride, c) is tetrabutylammonium bromide and the alkyl aryl ether is butyl phenyl ether (BPE).

14. The method of any one of claims 1-13, wherein reacting the reaction mixture is done in an anhydrous state.

15. The method of any one of claims 1-14, wherein the reaction mixture includes d) water in an amount less than 3 percent by weight based on the total weight of a), b), c) and d).

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