WO2015179088A1

WO2015179088A1 - Conversion of 5-(halomethyl)-2-furaldehyde into polyesters of 5-methyl-2furoic acid

Info

Publication number: WO2015179088A1
Application number: PCT/US2015/028143
Authority: WO
Inventors: Aviad Cahana; Timothy J. Martin; Timothy R. GEORGE
Original assignee: Xf Technologies Inc.
Priority date: 2014-05-22
Filing date: 2015-04-29
Publication date: 2015-11-26

Abstract

The present invention provides methods of synthesis of di-, tri-, and poly- ester derivatives of 5- methyl-2-furoic acid; di-, tri-, and poly- amide derivatives of 5-methyl-2-furoic acid; and di-, tri-, and poly- thioester derivatives of 5-methyl-2-furoic acid from 5-(halomethyl)-2-furaldehydes. These molecules are useful as plasticizers, solvents, coalescers, an ingredient in plastisol compositions, diluents, an ingredient in adhesive compositions, compatibilizer or compounding agent, or lubricant, as well as polymer compositions containing such ester compositions.

Description

CONVERSION OF 5-(HALOMETHYL)-2-FURALDEHYDE INTO POLYESTERS OF 5-METHYL-2-FUROIC ACID

[0001] Technical Field

[0002] The present invention describes the synthesis of di-, tri-, and poly- ester derivatives of 5- methyl-2-furoic acid; di-, tri-, and poly- amide derivatives of 5-methyl-2-furoic acid; and di-, tri-, and poly- thioester derivatives of 5-methyl-2-furoic acid from 5-(halomethyl)-2-furaldehydes. These molecules are useful as plasticizers, solvents, coalescers, an ingredient in plastisol compositions, diluents, an ingredient in adhesive compositions, compatibilizer or compounding agent, or lubricant, as well as polymer compositions containing such ester compositions.

[0003] Background Art

[0004] The synthesis of chemical products in more environmentally friendly and sustainable ways, a fundamental goal of green chemistry, has received increasing attention in recent years. Along with this, demand for new chemical products from renewable resources has also grown. The use of catalytic methods for chemical synthesis is one of the twelve principles of green chemistry, allowing for reduction of waste from the use of stoichiometric reagents. Following these goals, catalytic methods that allow for the production of new products from renewable resources will become increasingly important in the future.

[0005] 5-(chloromethyl)-2-furaldehyde (CM F) is a furan based chemical derived from biomass. CM F can be prepared in high yields from numerous renewable cellulosic and hemicellulosic feedstocks (See Mascal, M.; Nikitin, E. B. Energy & Fuels 2009, 24, 2170). Numerous studies and publications have detailed the synthesis of CMF, as well as its use as a platform chemical to produce specialty chemicals and fuel products. US Pat. No. 20140187802 Al, Mikochik et. al., details methods and apparatuses for the synthesis of CMF in high yields. US Pat. No. 8710250 B2, to Mikochik and Cahana, discloses a method for the creation of mono-ester derivatives of 5-methyl-2-furoic acid using a novel organocatalytic process from CMF and an alcohol.

[0006] /V-heterocyclic carbenes (N HCs) have been demonstrated to be efficient catalysts for numerous processes (See Enders, D.; Niemeier, O.; Hensler, A. Chem. Rev. 2007, 107, 5606; Moore, J. L; Rovis, T. Top. Curr. Chem. 2009, 290, 77), including the benzoin condensation (See Knight, R. L; Leeper, F. J. J. Chem. Soc, Perkin Trans. 1 1998, 1, 1891), the Stetter reaction (See Enders, D.;

Breuer, K.; Runsink, J.; Teles, J. H. Helv. Chim. Acta 1996, 79, 1899; Kerr, M. S.; Reid de Alaniz, J.; Rovis, T. J. Am. Chem. Soc. 2002, 124, 10298), and redox reactions (See Sohn, S. S.; Bode, J. W. Org. Lett. 2005, 7, 3873-3876; Reynolds, N. T.; Reid de Alaniz, J.; Rovis, T. J. Am. Chem. Soc. 2004, 126, 9518; Reynolds, N. T.; Rovis, T. J. Am. Chem. Soc. 2005, 127, 16406). Many processes involving N HC catalysis employ aldehydes as a reactant. Aldehydes are typically considered to be highly electrophilic, with a partial charge residing on the carbon atom. However, N HC catalysis is capable of reversing the charge of this carbon, which will now have a partial negative charge in the aldehyde- N HC adduct. Thus, N HC catalysis is capable of altering the reactivity of the aldehyde functional group, generally referred to as "umpolong" reactivity.

[0007] The present invention describes the high yielding synthesis of di-, tri-, and poly- ester derivatives of 5-methyl-2-furoic acid; di-, tri-, and poly- amide derivatives of 5-methyl-2-furoic acid; and di-, tri-, and poly- thioester derivatives of 5-methyl-2-furoic acid from 5-(halomethyl)-2- furaldehydes. This process utilizes NHC catalysis to obtain the desired molecules in high yields, ultimately from renewable feedstocks without requiring extreme temperatures or pressures. The molecules disclosed in this invention are useful as plasticizers, solvents, coalescers, an ingredient in plastisol compositions, diluents, an ingredient in adhesive compositions, compatibilizers or compounding agents, or lubricants. As such, the molecules produced in the disclosed method have the ability to serve as renewable replacements for their petroleum derived equivalents.

[0008] Solvents are substances that are capable of dissolving other substances. Numerous classes of organic compounds can be used as solvents, with a wide range of applications from cleaning to inks and paints to perfumes or chemical synthesis. Many organic solvents are petroleum derived, however there are growing examples of organic solvents derived from renewable resources and their applications.

[0009] Chlorinated solvents are widely used due to their effective cleaning and low flammability. These compounds are used across many industries, including metal finishing, automotive manufacturing, and electronic manufacturing. While these compounds are used extensively, some chlorinated solvents pose health and environmental risks, being either human carcinogens or ozone depleting compounds. Due to these concerns, there is a growing trend and regulatory momentum towards replacing chlorinated solvents with more environmentally friendly substitutes. A key challenge to this goal is finding renewable or environmentally friendly chemicals that are competitive or superior solvents and cleaners.

[0010] Polyvinyl chloride), or PVC, is a widely produced polymer with extensive applications. In 2013, about 39 million tons of PVC were used globally. Without modification, PVC is a rigid material useful in building materials. However, with the addition of plasticizers, PVC can become flexible and can be used for cable lining, medical applications, clothing, and finds expanded uses in building materials.

[0011] Plasticizers are organic liquids that will soften a polymer and make it more workable, provided the polymer and plasticizer are at least partially compatible. Plasticizers are used to adjust hardness and/or flexibility of a polymer by manipulating the glass transition temperature (T_g) of the polymer. They can also impart stain resistance, alter tensile properties (such as strength and elongation) and facilitate processing. Plasticizers are available in a wide variety of alternative chemistries and applications including: general plasticizers, film coalescers, d iluents plastisols, adhesives, and combatibilizers.

[0012] Phthalates are and have been the predominant type of plasticizer with widespread application by offering excellent compromise between performance and cost. However, environmental and toxicity concerns around the use of phthalates has led to increased demand for compounds that could serve as safer replacements for phthalates. The use of benzoate and toluate mono- and di- esters as plasticizers or diluents in polymer applications has been described in the prior art as alternatives to the use of phthalates.

[0013] U.S. Pat. No. 2585448 A discloses the synthesis of ester compositions of aliphatic or aromatic carboxylic acids with glycols or thioglycols and their use as plasticizers.

[0014] U.S. Pat. No. 4656214 discloses diesters that can be used as stain resistant plasticizers in PVC. Such diesters are derived from the reaction of aliphatic and aromatic carboxylic acids with diols containing between 2 and 8 carbon atoms.

[0015] U.S. Pat. No. 5990214 discloses liquid compositions of esters derived from benzoic or toluic acid with diethylene glycol or triethylene glycol and their use as plasticizers.

[0016] WO 02083621 Al discloses mixed esters from aliphatic and aromatic carboxylic acids and diols such as ethylene glycol and their use as plasticizers for PVC or other rigid organic polymers. The process disclosed is a single step building upon work from A.V. Bailey et. al. in the Journal of the American Oil Chemists Society, 53 (5): 176-8 (1976).

[0017] US Pat. No. 7718823 B2 discloses a method to produce toluate ester compositions from methyl-p-toluate and diols such as ethylene glycol, diethylene glycol, or triethylene glycol. The resultant mono- or di-esters can then be used as a solvent or plasticizer in polymer compositions.

[0018] US Pat. No. 20140102335 Al discloses the use of esters of furoic acid as bio-based plasticizers in surface covering compositions.

[0019] While the above ester mixtures can be used as plasticizers in polymer applications, the need exists for cost effective and environmentally friendly additives and plasticizers.

[0020] Hansen Solubility Parameters is a modeling theory known to those familiar with the state of the art. The Hansen Solubility Parameters of any chemical can be well characterized by just three parameters: 6D for Dispersion (van der Waals), δΡ for Polarity (related to dipole moment) and δΗ for hydrogen bonding. See Hansen Solubility Parameters: A User's Handbook, Second Edition, C. M. Hansen (2007), Taylor and Francis Group, LLC (HSPiP manual). Using these three parameters, any solvent, grouping of solvents or polymer can be plotted as a point in a 3D matrix (From Hansen Solubility Parameters in Practice HSPiP, Software). This point also has an interaction sphere, which is determined using a radius based on an extensive database of empirical relationships of solubility. Hansen Solubility Parameters may be referred to as the acronym HSP. Within HSP there is a primary value that is used to determine a solvent's similarity to any other solvent; this value is known as the RED. According to HSPiP, the provider for Hansen Solubility Parameter modeling software, "The RED number is the Relative Energy Difference and is simply the ratio of the distance of your solvent (blend) to the radius of the Sphere. A perfect solvent has a RED of 0. A solvent just on the surface of the Sphere has a RED of 1. It is a useful shorthand that gives quick insights into what's going on. Relative REDs are useful. If you have a solvent of RED 0.2 and another of 0.4 you know (a) that neither is perfect and (b) that the first one is better."

[0021] Description of Invention

[0022] The present invention describes the synthesis of polyesters of 5-methyl-2-furoic acid, polyamides of 5-methyl-2-furoic acid, and polythioester derivatives of 5-methyl-2-furoic acid from 5- (halomethyl)-2-furaldehyde. These molecules are useful as plasticizers, solvents, coalescers, an ingredient in plastisol compositions, diluents, an ingredient in adhesive compositions, compatibilizer or compounding agent, or lubricant, as well as polymer compositions containing such ester compositions. In an example embodiment, the first step comprises a method for the synthesis of an output containing a derivative of 5-methyl-2-furoic acid from a precursor comprising one or more of: 5-(chloromethyl)-2-furaldehyde, 5-(bromomethyl)-2-furaldehyde, 5-(iodomethyl)-2-furaldehyde, 5- (fluoromethyl)-2-furaldehyde, the method comprising: (a) contacting an excess of the precursor, a base, an organic solvent, a catalyst, and a multifunctional nucleophile in a reaction vessel at a temperature of from about 20 degrees Celsius to about 50 degrees Celsius, such that molecules of the output are produced; (b) separating the molecules of the output by extraction with a hydrophobic solvent, or else by chromatography, distillation, sublimation, or precipitation; wherein the catalyst is one or more of: (1) a /V-heterocyclic carbene, (2) a salt of a /V-heterocyclic carbene, (3) cyanide, (4) thiazolium, (5) 1,2,4-triazolium, (6) imidazolium, (7) tetrazolium ring system. The hydrophobic furan products can be purified by silica chromatography, distillation, sublimation, or precipitation. Hydrophilic furan products can be purified by distillation, sublimation, or precipitation. In some embodiments, the yield of glycol di-(5-methyl-2-furoates) is greater than 50% by this method. For example, in some embodiments, glycol di-(5-methyl-2-furoates) can include: ethylene glycol di-(5-methyl-2-furoate), triethylene glycol di-(5-methyl-2-furoate), and propylene glycol di-(5- methyl-2-furoate).

[0023] More specifically, in some embodiments the present invention relates to a method for the preparation of di- esters of 5-methyl-2-furoic acid having an alkoxycarbonyl portion, and wherein the alkoxycarbonyl portion is a linear or branched aliphatic chain and/or a cyclic aliphatic derived from a diol or glycol containing between 2 and 20 carbon atoms or di- esters of 5-methyl-2-furoic acid having an aryloxycarbonyl portion, and wherein the aryloxycarbonyl portion is one or more aromatic rings containing between 5 and 20 carbon atoms.

[0024] In some embodiments, the present invention provides di-esters of structure I, as shown in Fig. 1. Wherein "n" is an integer between 1 and 4, and R¹ is one of: hydrogen, a linear or branched aliphatic chain, a cyclic aliphatic, an aromatic ring, or multiple aromatic rings.

[0025] In an example embodiment, the first step comprises contacting a 5-(halomethyl)-2- furaldehyde precursor, a base, an organic solvent, a catalyst, and an excess of one or more of: a diol or glycol, diamine, or dithiol in a reaction vessel at a temperature of from about 0 degrees Celsius to about 50 degrees Celsius. Upon a suitable time for conversion of the precursor to the desired product, the reaction can be quenched with water and hydrophobic furan products can be separated by extraction with a hydrophobic solvent. The hydrophobic furan products can be purified by silica chromatography, distillation, sublimation, or precipitation. Hydrophilic furan products can be purified by distillation, sublimation, or precipitation. In some embodiments, the yield of glycol mono-(5-methyl-2-furoates) is greater than 50% by this method. For example, in some embodiments glycol mono-(5-methyl-2-furoates) may include: ethylene glycol mono-(5-methyl-2-furoate) or propylene glycol mono-(5-methyl-2-furoate). In an example embodiment, the method comprises the synthesis of an output containing a mono-ester glycol from a precursor comprising one or more of: 5-(chloromethyl)-2-furaldehyde, 5-(bromomethyl)-2-furaldehyde, 5-(iodomethyl)-2-furaldehyde, 5- (fluoromethyl)-2-furaldehyde, the method comprising: (a) contacting the precursor, a base, an organic solvent, a catalyst, and an excess of a diol of glycol in a reaction vessel at a temperature of from about 20 degrees Celsius to about 50 degrees Celsius, such that molecules of the output are produced; (b) separating the molecules of the output by extraction with a hydrophobic solvent, or else by chromatography, distillation, sublimation, or precipitation; wherein the catalyst is one or more of: (1) a /V-heterocyclic carbene, (2) a salt of a /V-heterocyclic carbene, (3) cyanide, (4) thiazolium, (5) 1,2,4-triazolium, (6) imidazolium, (7) tetrazolium ring system.

[0026] In some embodiments, the second step comprises contacting a glycol mono-(5-methyl-2- furoate), an organic solvent, a base, and one or more of: an alkanoyl halide or aroyl halide, in a reaction vessel at a temperature of from about 0 degrees Celsius to about 50 degrees Celsius. Upon a suitable time for conversion of the precursor to the desired product, the reaction can be quenched with water and hydrophobic mixed ester products can be separated by extraction with a hydrophobic solvent. Hydrophobic mixed ester products can be purified by silica chromatography, distillation, sublimation, or precipitation. Hydrophilic furan products can be purified by distillation, sublimation, or precipitation. In some embodiments, the yield of mixed ester is greater than 50% by this method. For example, in some embodiments, the method provides mixed di-esters of structure II, as shown in Fig. 2. Wherein "n" is an integer between 1 and 4 and R² is a linear or branched aliphatic chain and/or a cyclic aliphatic, containing between 1 and 20 carbon atoms and R³ is one of: hydrogen, a linear or branched aliphatic chain, a cyclic aliphatic, an aromatic ring, or multiple aromatic rings. Additionally, di-esters of structure II wherein "n" is an integer between 1 and 4 and R² is an aromatic ring containing between 5 and 10 carbon atoms and R³ is one of: hydrogen, a linear or branched aliphatic chain, a cyclic aliphatic, an aromatic ring, or multiple aromatic rings.

[0027] In other example embodiments, the second step of the present invention comprises contacting a glycol mono-(5-methyl-2-furoate), an organic solvent, a base, and one or more of: an acylation reagent, a phosphorylation reagent, a silylation reagent.

[0028] Further embodiments can include diols, diamines, or dithiols with additional functionality. For example, additional functional groups can include but are not limited to amides, alkenes, alkynes, esters, ethers, ketones, nitriles, phosphates, or sulfates. One skilled in the art can appreciate the compatibility of such functional groups with the current method.

[0029] Other example embodiments of the present invention can provide tri-, or tetra-, or other poly- esters of 5-methyl-2-furoic acid. Triesters of 5-methyl-2-furoic acid can also find use in the described applications. In some embodiments, the output contains a triester of 5-methyl-2-furoic acid from a precursor comprising one or more of: 5-(chloromethyl)-2-furaldehyde, 5-(bromomethyl)- 2-furaldehyde, 5-(iodomethyl)-2-furaldehyde, 5-(fluoromethyl)-2-furaldehyde, the method comprising: (a) contacting an excess of the precursor, a base, an organic solvent, a catalyst, and a triol in a reaction vessel at a temperature of from about 20 degrees Celsius to about 50 degrees Celsius, such that molecules of the output are produced; (b) separating the molecules of the output by extraction with a hydrophobic solvent, or else by chromatography, distillation, sublimation, or precipitation; wherein the catalyst is one or more of: (1) a /V-heterocyclic carbene, (2) a salt of a N- heterocyclic carbene, (3) cyanide, (4) thiazolium, (5) 1,2,4-triazolium, (6) imidazolium, (7) tetrazolium ring system. In some embodiments the present invention can provide di-, tri-, or poly- amides of 5-methyl-2-furoic acid, also useful in the described applications. In other embodiments, the present invention can provide di-, tri-, or poly- thioesters of 5-methyl-2-furoic acid, also useful in the described applications. Further still some embodiments of the present invention can provide mixed ester-amides, ester-thioesters, and amide-thioesters of 5-methyl-2-furoic acid, also useful in the described applications.

[0030] As used herein, the term "derivative of 5-methyl-2-furoic acid" refers to one of: a polyester of 5-methyl-2-furoic acid, a polyamide of 5-methyl-2-furoic acid, a polythiol of 5-methyl-2-furoic acid. A "polyester of 5-methyl-2-furoic acid" refers to a compound containing more than one ester of 5-methyl-2-furoic acid. For example, a diester of 5-methyl-2-furoic acid is considered a "polyester of 5-methyl-2-furoic acid". A "polyamide of 5-methyl-2-furoic acid" refers to a compound containing more than one amide of 5-methyl-2-furoic acid. For example, a diamide of 5-methyl-2-furoic acid is considered a "polyamide of 5-methyl-2-furoic acid". A "polythioester of 5-methyl-2-furoic acid" refers to a compound containing more than one thioester of 5-methyl-2-furoic acid. For example, a dithioester of 5-methyl-2-furoic acid is considered a "polythioester of 5-methyl-2-furoic acid".

[0031] As used herein, the term "catalyst" refers to any atom or molecule that is present in sub- stoichiometric amounts relative to CMF, which is able to affect the desired chemical transformation of CMF to di-, tri-, and poly- ester derivatives of 5-methyl-2-furoic acid; di-, tri-, and poly- amide derivatives of 5-methyl-2-furoic acid; and di-, tri-, and poly- thioester derivatives. The catalyst can also be present in super-stoichiometric amounts relative to CM F.

[0032] As used herein, the term "N-heterocyclic carbene (NHC)" refers to any polycyclic or heterocyclic organic molecules, which contains at least two non-carbon atoms, which include one nitrogen, and one or more from the following: nitrogen, sulfur, phosphorus, or silicon; as well as at least one carbon atom. These atoms are arranged in such a way that upon treatment with an anhydrous base, a singlet carbene will form on a carbon atom contained within the heterocyclic ring.

[0033] As used herein, the term "singlet carbene" refers to a carbon atom bonded to two substituents, with the remaining atomic orbital geometry comprising an s-orbital bearing two electrons, and an empty p-orbital.

[0034] As used herein, the term "multifunctional nucleophile" refers to a molecule containing two or more groups capable of acting as a nucleophile. The term "nucleophile" refers to organic molecules that contain a reactive electronegative element. Examples of multifunctional nucleophiles useful in this invention included, but are not limited to: polyols, polyamines, and polythiols.

[0035] As used herein, the term "polyol" refers to an organic molecule that contains more than one hydroxyl group, such as diols and triols. A "diol" refers to an organic molecule that contains two hydroxyl groups. Diols useful in the current invention include, but are not limited to: ethylene glycol, propylene glycol, 1,4-butanediol, triethylene glycol, and 1,4-benzenediol. The term "triol" refers to an organic molecule that contains three hydroxyl groups. Triols useful in the current invention include but are not limited to: glycerol and benzenetriol.

[0036] As used herein, the term "base" refers to molecules capable of neutralizing acidic species. Types of bases especially useful in this reaction included inorganic bases and nitrogen containing organic bases. Bases useful in the current invention include, but are not limited to, sodium carbonate, potassium carbonate, triethyl amine, l,8-diazabicyclo[5.4.0]undec-7-ene (DBU), pyridine, sodium bicarbonate, potassium bicarbonate, and sodium acetate. A base can be present in any useful concentration in the present invention. For example, it can occur from super-stoichiometric quantities with respect to the moles of CMF, up to equimolar or sub-stoichiometric quantities.

[0037] As used herein, the term "organic solvent" refers to solvents that are carbon-based and generally, non-polar, polar aprotic, or polar protic. Organic solvents useful in the current invention include, but are not limited to, ethyl acetate, tetrahydrofuran, diethyl ether, hexane, toluene, methyl 5-methyl 2-furoate, ethyl 5-methyl 2-furoate, halogenated solvents such as

dichloromethane, 1,2-dichloroethane, or combinations thereof. As used herein, the term

"hydrophobic solvent" refers to organic solvents that are immiscible with water.

[0038] As used herein, alkanoyl halide or aroyl halide refer to molecules of structure III, illustrated in Fig. 3, wherein X is one of: fluoride, chloride, bromide, iodide, acetoxy, trimethylacetoxy, trifluoroacetoxy.

[0039] "R" of structure III can be one of: a linear or branched aliphatic chain and/or a cyclic aliphatic, containing between 1 and 20 carbon atoms, an aromatic ring or rings containing between 1 and 20 carbon atoms. Alkanoyl halides and aroyl halides useful in the current invention include, but are not limited to, acetyl chloride, lauroyl chloride, benzoyl choride, and p-toluoyl chloride.

[0040] A method of the present invention can also include other components and reagents known to one skilled in the art. For example, other components and reagents can include buffers, surfactants, additional salts, and additional solvents.

[0041] Brief Description of the Drawings

[0042] The accompanying drawings, which are incorporated in and form part of the specification, illustrate the present invention and, together with the description, describe the invention.

[0043] Fig. 1 is a schematic illustration of di-esters of structure I.

[0044] Fig. 2 is a schematic illustration of mixed di-esters of structure II.

[0045] Fig. 3 is a schematic illustration of molecules of structure III.

[0046] Modes for Carrying Out the Invention and Industrial Applicability

[0047] In an example embodiment, the current invention provides triethylene glycol di-(5-methyl-2- furoate) as follows: CMF (3.00 g, 20.8 mmol) was dissolved in ethyl acetate (20 ml), and stirred at 24° C. Sodium carbonate (3.1 g, 29.12 mmol) was added, followed by 2-(2,3,4,5,6-pentafluorophenyl)- 6,7-dihydro-5H-pyrrolo[2,l-c] [l,2,4]triazol-2-ium tetrafluoroborate (0.019 g, 0.052 mmol) and triethylene glycol (1.1 ml, 8.04 mmol). Stirring was continued for 16 hours, during which time the reaction took on a light brown color. 1.0 M HCI (aqueous, 50 ml) was then added, and the reaction extracted with ethyl acetate (3x25 ml). The combined organic extracts were pooled and washed with brine. Desiccation over Na₂S0₄ and solvent evacuation preceded precipitation of the product (7 ml ethyl acetate: 7 ml hexanes), which furnished the ester as a tan solid (165 g, 56% yield): ¹H N MR δ (acetone- /₆): 7.10 (d, 2H, J = 3.5 Hz), 6.23 (d, 2H, J = 3.5 Hz), 4.33 (dd, 4H, J = 4.5 Hz), 3.75 (dd, 4H, J = 4.5 Hz),3.63 (s, 4H), 2.33 (s, 6H).

[0048] In an example embodiment, the current invention provides ethylene glycol mono-(5-methyl- 2-furoate) as follows: CMF (3.00 g, 20.8 mmol) was dissolved in ethyl acetate (20 ml), and stirred at 24° C. Triethyl amine (5.8 mL, 41.6 mmol) was added, followed by 2-(2,6-difluorophenyl)imidazo[l,5- a]pyridinium chloride (0.19 g, 0.52 mmol) and ethylene glycol (5.8 ml, 62.4 mmol). The reaction mixture was heated to 39° C and stirring was continued for 24 hours. 1.0 M HCI (aqueous, 50 ml) was then added, and the reaction extracted with ethyl acetate (3x25 ml). The combined organic extracts were pooled and washed with brine. Desiccation over Na₂S0₄ and solvent evacuation preceded silica chromatography of the residue (25% ethyl acetate:hexanes), which furnished the mono-ester glycol as an orange oil (2.3 g, 65% yield): ^XH N MR δ (acetone- /₆): 7.12 (d, 2H, J = 3.5 Hz), 6.23 (d, 2H, J = 3.5 Hz), 4.29 (t, 2H, J = 5 Hz), 3.79 (m, 2H), 2.33 (s, 3H).

[0049] Outputs of the invention find uses in a variety of fields and applications. Some of these applications are in compositions of solvents, plasticizers, film coalescers, plastisols, diluents, adhesives, sealants, caulks, lubricants, corrosion inhibitors, polymer combatibilizers, electrolytes for ion batteries and other energy storage devices, insecticides, herbicides, and emollients in cosmetics. By comparing the output of the invention with known chemicals performing in these applications using Hansen Solubility Parameters a baseline evaluation of their performance in similar applications can be determined.

[0050] Solvents are distributed mainly within but not limited to two major industries: cleaning solvents and processing solvents. Cleaning solvents are those applied to remove soils from surfaces or to dissolve unwanted products from a system as evidenced in enhanced oil recovery operations. Processing solvents are used to aid in or act as mediums for conducting chemical synthesis. There will generally be additional factors that must be evaluated for solvent efficacy such as safety, environmental impact, physical properties, thermal and oxidative stability etc. in order to properly design the solvent's use per application.

[0051] Example 1:

[0052] Two examples of prominent cleaning solvents used today are methylene chloride (DCM) and n-propyl Bromide (nPB); the compared HSP values indicate similar utility in cleaning various soils. These comparisons are shown with the understanding that there are many other considerations to evaluate before an ideal cleaning composition can be chosen for each particular application. [0053] Table 1. Shows RED value of certain outputs of the invention compared with 1- Bromopropane being the target or origin with an RED of 0.

Solvent RED

1-Bromopropane 0

Tri-ethylene glycol di-5-methyl-2-furoate 0.21

Diethylene glycol di-5-methyl-2-furoate 0.24

Propylene glycol di-5-methyl-2-furoate 0.28

Table 2. Shows RED value of certain outputs of the invention compared with methylene chloride being the target or origin with an RED of 0.

Solvent RED

Methylene Dichloride (Dichloromethane) 0

Triethylene glycol di-5-methyl-2-furoate 0.24

Diethylene glycol di-5-methyl-2-furoate 0.26

Propylene glycol di-5-methyl-2-furoate 0.32

[0054] Example 2

[0055] Oftentimes certain polymer applications require specific plasticizer formulations for each particular application and this can include blending various plasticizers into the polymer melt.

Certain outputs of the invention fall closely within solubility of several other plasticizer families; such outputs of the present invention can serve as replacements or be blended into compositions with other plasticizer groups such as but not limited to phthalates, orthophthalates, terephthalates, cyclohexanoates, adipates, phosphate esters, trimellitates, sebacates, azelates, citrates, benzoates, dibenzoates, and fatty acid/vegetable oil based plasticizers. Several examples in the tables below show how much solubility is shared between embodiments of the invention compared to various members of the different plasticizer families.

Table 4. Shows RED value of embodiments of the invention compared to triethylene glycol dibenzoate, another prominent plasticizer from the benzoate class, with triethylene glycol dibenzoate being the target or origin with a RED of 0.

Plasticizer RED

triethylene glycol di-benzoate 0

diethylene glycol di-5-methyl-2-furoate 0.07

triethylene glycol di-5-methyl-2-furoate 0.14

propylene glycol di-5-methyl-2-furoate 0.17

Table 5. Shows RED value of embodiments of the invention compared to d iethylene glycol dibenzoate, another prominent plasticizer from the benzoate class, with diethylene glycol dibenzoate being the target or origin with a RED of 0.

Plasticizer RED

diethylene glycol di-benzoate 0

propylene di-5-methyl-2-furoate 0.12

diethylene glycol d i-5-methyl-2-furoate 0.17

Quinol di-5-methyl-2-furoate 0.28

Table 6. Shows RED value of embodiments of the invention compared to Acetyl Triethyl Citrate, another prominent plasticizer, with Acetyl Triethyl Citrate being the target or origin with a RED of 0.

Plasticizer RED

Acetyl Triethyl Citrate 0

propylene glycol mono-5-methyl-2-furoate 0.7

triethylene glycol mono-5-methyl-2-furoate 0.72

triethylene glycol di-5-methyl-2-furoate 0.73

diethylene glycol d i-5-methyl-2-furoate 0.77

propylene glycol di-5-methyl-2-furoate 0.77 Table 7. Shows RED value of embodiments of the invention compared to Triisooctyl Trimellitate, another prominent plasticizer, with Triisooctyl Trimellitate being the target or origin with a RED of 0.

Plasticizer RED

Triisooctyl Trimellitate 0

propylene glycol di-5-methyl-2-furoate 0.46

BPA d i-5-methyl-2-furoate 0.53

diethylene glycol di-5-methyl-2-furoate 0.55

triethylene glycol di-5-methyl-2-furoate 0.57

Table 8. Shows RED value of an embodiment of the invention compared to Di(2-Ethylhexyl) Adipate, another prominent plasticizer, with Di(2-Ethylhexyl) Adipate being the target or origin with a RED of

0.

Plasticizer RED

Di(2-Ethylhexyl)Adipate 0

propylene glycol di-5-methyl-2-furoate 0.81

BPA d i-5-methyl-2-furoate 0.81

diethylene glycol d i-5-methyl-2-furoate 0.88

Table 9. Shows RED value of an embodiment of the invention compared to Tri-n-Butyl Phosphate, another prominent plasticizer, with Tri-n-Butyl Phosphate being the target or origin with a RED of 0.

Plasticizer RED

Tri-n-Butyl Phosphate 0

propylene glycol di-5-methyl-2-furoate 0.38

triethylene glycol di-5-methyl-2-furoate 0.4

diethylene glycol d i-5-methyl-2-furoate 0.41

[0056] Example 3

[0057] Certain outputs of the invention can also find use as machine, manufacturing, and engine lubricants and/or cutting fluids for applications requiring good thermal stability and high lubricating/cooling properties. In much of manufacturing lubricants and cutting fluids are necessary to protect the work piece and maintain thermal stability, increasing the lifetime of the machining tool, and ensure worker safety. In d ifferent contexts machine lubricants can be referred to as cutting fluids, cutting oils, cutting compounds, coolants, and/or lubricants. In the application of machining lubricants and/or coolants chlorinated alkanes or paraffins are broadly used in various compounds and commercial mixtures. Due to toxicity, chlorinated paraffins are being replaced due to health concerns and regulatory pressure. Certain outputs of the present invention can be used to supplement or replace certain chlorinated alkanes or other lubricating compounds used in manufacturing or as lubricating additives.

Table 10 Shows RED value of embodiments of the invention compared to a primary metal working lubricant component 1,2,3,4,6,7,10-heptachlorododecane, with 1,2,3,4,6,7,10-heptachlorododecane being the target or origin with a RED of 0.

Lubricant RED

1,2,3,4,6,7,10-Heptachlorododecane 0

BPA di-5-methyl-2-furoate 0.39

Quinol di-5-methyl-2-furoate 0.63

propylene glycol di-5-methyl-2-furoate 0.66

[0058] Example 4

[0059] Lithium ion batteries have been a staple of battery technology due to their relatively lightweight and high energy density profiles. These batteries among others require an electrolyte, which in the case of lithium batteries consist of various lithium salts in an organic solvent, such as ethylene carbonate, dimethyl carbonate, and diethyl carbonate. These liquid electrolytes act as a carrier between the positive and negative electrodes when current flows through an external circuit. Some examples of how closely several outputs of the current invention match solvency with current electrolytes are shown below. In addition to the similar compatibility as existing carbonate solvents, the outputs of the invention can also exhibit other specific behaviors. For instance high conductivity and acceptable SE!-forming ability. The SE! refers to a barrier that forms when the solvent decomposes on initial charging and forms a solid layer called the Solid Electrolyte Interphase (SE!), which is electrically insulating yet provides significant ionic conductivity. The interphase prevents further decomposition of the electrolyte, which is critical to the life of the battery. Shown below are several examples of the similar compatibility certain outputs of the invention to several carbonate solvents. Table 12 Shows RED value of embodiments of the invention compared to a primary lithium ion battery electrolyte dimethyl carbonate with dimethyl carbonate being the target or origin with a RED of 0.

Electrolyte RED

Dimethyl Carbonate 0

triethylene glycol mono-5-methyl-2-furoate 0.31

diethylene glycol mono-5-methyl-2-furoate 0.42

propylene glycol mono-5-methyl-2-furoate 0.51

triethylene di-5-methyl-2-furoate 0.54

ethylene glycol mono-5-methyl-2-furoate 0.57

diethylene glycol di-5-methyl-2-furoate 0.64

Table 13 Shows RED value of embodiments of the invention compared to a primary lithium ion battery electrolyte diethyl carbonate, with diethyl carbonate being the target or origin with a RED of

0.

Electrolyte RED

Diethyl Carbonate 0

triethylene glycol di-5-methyl-2-furoate 0.6

diethylene glycol di-5-methyl-2-furoate 0.65

propylene glycol di-5-methyl-2-furoate 0.66

[0060] Some outputs of the invention can find use as skin-conditioning agents, known as emollients. Emollients are used to make the external layers of skin softer and more pliable. Such agents can comprise a wide variety of cosmetic products including baby products, bath products, eye makeup, lipstick, shaving products, suntan products, hair care products, and nail care and skin care products. C12-15 Alkyl Benzoate and the other long-chain alkyl benzoate ingredients are already commonly used to this affect and this group of molecules exhibit similar properties as outputs of the invention. As an example of how the embodiments of the invention can also be similarly functional, the HSP of human skin is shown below compared to several embodiments as well as common benzoates used in emollients. Table 11 Shows RED value of embodiments of the invention compared to a primary lithium ion battery electrolyte dimethyl carbonate with dimethyl carbonate being the target or origin with a RED of 0.

Emollient RED

Human Skin 0

ethylene glycol mono-5-methyl-2-furoate 0.37

diethylene glycol mono-5-methyl-2-furoate 0.42

triethylene glycol mono-5-methyl-2-furoate 0.5

propylene glycol mono-5-methyl-2-furoate 0.51

triethylene glycol di-5-methyl-2-furoate 0.8

diethylene glycol di-5-methyl-2-furoate 0.82

[0061] Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, one of skill in the art will appreciate that certain changes and modifications may be practiced within the scope of the appended claims. In addition, each reference provided herein is incorporated by reference in its entirety to the same extent as if each reference was individually incorporated by reference.

Claims

Claims What is claimed is:

1. A method for the synthesis of an output containing a derivative of 5-methyl-2-furoic from a precursor comprising one or more of: 5-(chloromethyl)-2-furaldehyde, 5-(bromomethyl)-2- furaldehyde, 5-(iodomethyl)-2-furaldehyde, 5-(fluoromethyl)-2-furaldehyde, the method comprising: (a) contacting an excess of the precursor, a base, an organic solvent, a catalyst, and a multifunctional nucleophile in a reaction vessel at a temperature of from about 20 degrees Celsius to about 50 degrees Celsius, such that molecules of the output are produced; (b) separating the molecules of the output by extraction with a hydrophobic solvent, or else by chromatography, distillation, sublimation, or precipitation; wherein the catalyst is one or more of: (1) a /V-heterocyclic carbene, (2) a salt of a /V-heterocyclic carbene, (3) cyanide, (4) thiazolium, (5) 1,2,4-triazolium, (6)

imidazolium, (7) tetrazolium ring system.

2. A method as in claim 1, wherein the output contains a di-ester of 5-methyl-2-furoic acid from a precursor comprising one or more of: 5-(chloromethyl)-2-furaldehyde, 5-(bromomethyl)-2- furaldehyde, 5-(iodomethyl)-2-furaldehyde, 5-(fluoromethyl)-2-furaldehyde, the method comprising: (a) contacting an excess of the precursor, a base, an organic solvent, a catalyst, and a diol in a reaction vessel at a temperature of from about 20 degrees Celsius to about 50 degrees Celsius, such that molecules of the output are produced; (b) separating the molecules of the output by extraction with a hydrophobic solvent, or else by chromatography, distillation, sublimation, or precipitation; wherein the catalyst is one or more of: (1) a /V-heterocyclic carbene, (2) a salt of a /V-heterocyclic carbene, (3) cyanide, (4) thiazolium, (5) 1,2,4-triazolium, (6) imidazolium, (7) tetrazolium ring system.

3. A method as in claim 1, wherein the output contains a di-ester of 5-methyl-2-furoic acid having an alkoxycarbonyl portion, and wherein the alkoxycarbonyl portion comprises one or more of: a linear aliphatic chain, a branched aliphatic chain, and a cyclic aliphatic derived from a diol or glycol having at least 2 and not more than 12 carbon atoms.

4. A method as in claim 1, wherein the output is a di-ester of 5-methyl-2-furoic acid having an aryloxycarbonyl portion, and wherein the aryloxycarbonyl portion comprises one or more aromatic rings containing between 5 and 20 carbon atoms.

5. A method as in claim 1, wherein the output contains a tri-ester of 5-methyl-2-furoic acid from a precursor comprising one or more of: 5-(chloromethyl)-2-furaldehyde, 5-(bromomethyl)-2- furaldehyde, 5-(iodomethyl)-2-furaldehyde, 5-(fluoromethyl)-2-furaldehyde, the method comprising: (a) contacting an excess of the precursor, a base, an organic solvent, a catalyst, and a triol in a reaction vessel at a temperature of from about 20 degrees Celsius to about 50 degrees Celsius, such that molecules of the output are produced; (b) separating the molecules of the output by extraction with a hydrophobic solvent, or else by chromatography, distillation, sublimation, or precipitation; wherein the catalyst is one or more of: (1) a /V-heterocyclic carbene, (2) a salt of a /V-heterocyclic carbene, (3) cyanide, (4) thiazolium, (5) 1,2,4-triazolium, (6) imidazolium, (7) tetrazolium ring system.

6. A method as in claim 1, wherein the base is an inorganic base.

7. A method as in claim 1, wherein the base is a nitrogen-containing organic base.

8. A method for the synthesis of an output containing a mono-ester glycol from a precursor comprising one or more of: 5-(chloromethyl)-2-furaldehyde, 5-(bromomethyl)-2-furaldehyde, 5- (iodomethyl)-2-furaldehyde, 5-(fluoromethyl)-2-furaldehyde, the method comprising: (a) contacting the precursor, a base, an organic solvent, a catalyst, and an excess of a diol or glycol in a reaction vessel at a temperature of from about 20 degrees Celsius to about 50 degrees Celsius, such that molecules of the output are produced; (b) separating the molecules of the output by extraction with a hydrophobic solvent, or else by chromatography, distillation, sublimation, or precipitation;

wherein the catalyst is one or more of: (1) a /V-heterocyclic carbene, (2) a salt of a /V-heterocyclic carbene, (3) cyanide, (4) thiazolium, (5) 1,2,4-triazolium, (6) imidazolium, (7) tetrazolium ring system.

9. A method as in claim 8, wherein the output is a mono-ester glycol of 5-methyl-2-furoic acid having an alkoxycarbonyl portion, and wherein the alkoxycarbonyl portion is one or more of: a linear aliphatic chain, a branched aliphatic chain, and a cyclic aliphatic derived from a diol or glycol having at least 2 and not more than 12 carbon atoms.

10. A method as in claim 8, wherein the output is a mono-ester glycol of 5-methyl-2-furoic acid having an aryloxycarbonyl portion, and wherein the aryloxycarbonyl portion comprises one or more aromatic rings having at least 5 and not more than 20 carbon atoms.

11. A method as in claim 8, wherein the base is an inorganic base.

12. A method as in claim 8, wherein the base is a nitrogen-containing organic base.

13. A method for the synthesis of an output containing one or more of: a mono-ester glycol or a mixed diester glycol from a precursor comprising a mono-ester glycol, the method comprising: (a) contacting the precursor, a base, an organic solvent, and an acid halide in a reaction vessel at a temperature of from about 20 degrees Celsius to about 50 degrees Celsius, such that molecules of the output are produced; (b) separating the molecules of the output by extraction with a hydrophobic solvent, or else by chromatography, distillation, sublimation, or precipitation.

14. A method as in claim 13, wherein the base is an inorganic base.

15. A method as in claim 13, wherein the base is a nitrogen-containing organic base.