Electrochemical synthesis of 2-methyl-tetrahydrofuran and 1,4-pentanediol from levulinic acid derived esters and gamma-valerolactone

Abstract

Disclosed herein are electrochemical methods for preparing 2-Methyltetrahydrofuran (MTHF), 1,4-Pentanediol (PDOL), and combinations thereof.

Description

[0001] Attorney Docket No. 11255-037WO1

[0002] CU Ref.: 2025-057

[0003] ELECTROCHEMICAL SYNTHESIS OF 2-METHYL- TETRAHYDROFURAN AND 1,4-PENTANEDIOL FROM LEVULINIC ACID DERIVED ESTERS AND GAMMA-VALEROLACTONE

[0004] CROSS-REFERENCE TO RELATED APPLICATIONS

[0005] This application claims benefit of priority of U.S. Provisional Application No. 63 / 697,427, filed September 20, 2024, and U.S. Provisional Application No. 63 / 767,477, filed March 5, 2025, which is incorporated by reference in its entirety.

[0006] STATEMENT OF GOVERNMENT SUPPORT

[0007] This invention was made with government support under CBET grant number 2301381 awarded by the National Science Foundation. The government has certain rights in the invention.

[0008] BACKGROUND

[0009] Levulinic acid (LA) is a key platform chemical derived from biomass, typically sourced from agricultural waste and lignocellulosic materials. It serves as the foundation for producing various renewable chemicals and biofuels. One of the most promising derivatives of LA is gamma-valerolactone (GVL), a renewable solvent with applications in biofuel production and green chemistry. GVL can be further converted into 2-methyltetrahydrofuran (MTHF), a high- performance biofuel additive.

[0010] MTHF is a versatile and renewable fuel additive that can be blended with gasoline, making it an attractive alternative to fossil fuel-derived additives. Its ability to integrate seamlessly with existing fuel infrastructure makes it ideal for the biofuels industry, offering improvements in fuel efficiency, reduced emissions, and enhanced fuel stability. Beyond fuel applications, MTHF is also used in green solvents, contributing to cleaner industrial processes by replacing toxic petrochemical solvents.

[0011] Another important chemical derived from the electrochemical conversion of LA through GVL is 1 ,4-pentanediol (PDOL). PDOL is widely used in the production of bioplastics, polyurethanes, and resins, providing a sustainable alternative to traditional petroleum-based Attorney Docket No. 11255-037WO1

[0012] CU Ref.: 2025-057 materials. Its applications in packaging, coatings, and adhesives support the growing demand for biodegradable and eco-friendly materials in various industries.

[0013] Currently, the industrial-scale production of MTHF and PDOL relies heavily on catalytic hydrogenation and petrochemical-based processes. MTHF is typically produced from furfural or levulinic acid through multi-step reactions involving precious metal catalysts like palladium and high-pressure hydrogen. Similarly, PDOL is commonly produced via petroleum-derived intermediates, requiring high-temperature, high-pressure catalytic processes. These methods, while effective, are expensive and resource-intensive due to the use of noble metals and hydrogen.

[0014] Improved methods of preparing 2-Methyltetrahydrofuran (MTHF) and 1 ,4-Pentanediol (PDOL) are therefore needed.

[0015] SUMMARY

[0016] In accordance with the purposes of the disclosed compositions, devices, methods, and systems as embodied and broadly described herein, the disclosed subject matter relates to electrochemical synthesis of 2-Methyltetrahydrofuran (MTHF),1,4-Pentanediol (PDOL), or a combination thereof.

[0017] For example, provided herein are methods for preparing 2-methyltetrahydrofuran (MTHF), 1 ,4-pentanediol (PDOL), or a combination thereof from hydroxyvaleric acid. These methods can comprise esterifying the hydroxyvaleric acid to form gamma- valerolactone; contacting a solution of the gamma-valerolactone with a second anode and a second cathode in a second electrochemical cell; and electrochemically reducing the gamma-valerolactone at the second cathode to form the MTHF, PDOL, or a combination thereof.

[0018] In some embodiments, esterifying the hydroxy valeric acid to form gamma-valerolactone comprises an acid-catalyzed esterification.

[0019] In some embodiments, electrochemically reducing the gamma-valerolactone at the second cathode to form the MTHF, PDOL, or a combination thereof produces MTHF as a major (primary) product. In some embodiments, the solution of the gamma-valerolactone has a pH of from 1 to 8, such as from 1 to 7, from 1 to 6, from 1 to 5, from 1 to 4, from 2 to 8, from 2 to 7, from 2 to 6, from 2 to 5, or from 2 to 4. In some embodiments, the solution of the gamma- valerolactone comprises an aqueous solution comprising water, gamma-valerolactone, and one or more electrolytes. In some embodiments, the second anode, the second cathode, or a combination thereof comprise copper or a platinum group metal. Attorney Docket No. 11255-037WO1

[0020] CU Ref.: 2025-057

[0021] In other embodiments, electrochemically reducing the gamma-valerolactone at the second cathode to form the MTHF, PDOL, or a combination thereof produces PDOL as a major (primary) product. In some embodiments, the solution of the gamma-valerolactone has a pH of from 7 to 14, such as from 8 to 14, from 9 to 14, from 10 to 14, from 11 to 14, from 7 to 12, such as from 8 to 12, from 9 to 12, from 10 to 12, or from 11 to 12. In some embodiments, the solution of the gamma-valerolactone comprises an aqueous solution comprising water, gamma- valerolactone, and one or more electrolytes. In some embodiments, the second anode, the second cathode, or a combination thereof comprise copper or a platinum group metal.

[0022] In some embodiments, the method further comprises contacting a solution of levulinic acid with a first anode and a first cathode in a first electrochemical cell; and electrochemically reducing the levulinic acid at the first cathode to form the hydroxyvaleric acid.

[0023] In some embodiments, the method is performed as a one-pot process.

[0024] Also provided herein are methods for preparing 1 ,4-pentanediol (PDOL). These methods can comprise esterifying the hydroxyvaleric acid to form a hydroxyvaleric acid ester; contacting a solution of the hydroxyvaleric acid ester with a second anode and a second cathode in a second electrochemical cell; and electrochemically reducing the hydroxyvaleric acid ester at the second cathode to form the PDOL.

[0025] In some embodiments, esterifying the hydroxy valeric acid to form the hydroxy valeric acid ester comprises an acid-catalyzed esterification.

[0026] In some embodiments, the hydroxyvaleric acid ester comprises a hydroxyvaleric acid alkyl ester.

[0027] In some embodiments, the solution of the hydroxyvaleric acid ester further comprises a proton donor, such as ammonia, methanol, ethanol, ethylene glycol, or dimethylurea.

[0028] In some embodiments, the solution of the hydroxyvaleric acid ester further comprises a base, such as 1,3 -dimethylurea, triethanolamine, trimethylamine, triethylamine, Piperidine, 2,2- bipyridine, N-methylphthalimide, or N,N-diisopropylethylamine.

[0029] In some embodiments, the solution of the hydroxyvaleric acid ester further comprises a solvent, such as an organic solvent (e.g., THF).

[0030] In some embodiments, the method further comprises contacting a solution of levulinic acid with a first anode and a first cathode in a first electrochemical cell; and electrochemically reducing the levulinic acid at the first cathode to form the hydroxyvaleric acid.

[0031] In some embodiments, the method is performed as a one-pot process. Attorney Docket No. 11255-037WO1

[0032] CU Ref.: 2025-057

[0033] Also provided herein are methods for preparing 1 ,4-pentanediol (PDOL). These methods can comprise esterifying levulinic acid to from a levulinic acid ester; contacting a solution of the levulinic acid ester with a first anode and a first cathode in a second electrochemical cell; electrochemically reducing the levulinic acid ester at the first cathode to form a hydroxyvaleric acid ester; contacting a solution of the hydroxyvaleric acid ester with a second anode and a second cathode in a second electrochemical cell; and electrochemically reducing the hydroxyvaleric acid ester at the second cathode to form the PDOL.

[0034] In some embodiments, esterifying the levulinic acid to form the levulinic acid ester comprises an acid-catalyzed esterification.

[0035] In some embodiments, the levulinic acid ester comprises a levulinic acid alkyl ester.

[0036] In some embodiments, the solution of the hydroxyvaleric acid ester further comprises a proton donor, such as ammonia, methanol, ethanol, ethylene glycol, or dimethylurea.

[0037] In some embodiments, the solution of the hydroxyvaleric acid ester further comprises a base, such as 1,3 -dimethylurea, triethanolamine, trimethylamine, triethylamine, Piperidine, 2,2- bipyridine, N-methylphthalimide, or N,N-diisopropylethylamine.

[0038] In some embodiments, the solution of the hydroxyvaleric acid ester further comprises a solvent, such as an organic solvent (e.g., THF).

[0039] In some embodiments, the method is performed as a one-pot process.

[0040] Additional advantages of the disclosed compositions, devices, systems, and methods will be set forth in part in the description which follows, and in part will be obvious from the description. The advantages of the disclosed compositions, devices, systems, and methods will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the disclosed compositions, devices, systems, and methods, as claimed.

[0041] The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims. Attorney Docket No. 11255-037WO1

[0042] CU Ref.: 2025-057

[0043] BRIEF DESCRIPTION OF THE FIGURES

[0044] The accompanying figures, which are incorporated in and constitute a part of this specification, illustrate several aspects of the disclosure, and together with the description, serve to explain the principles of the disclosure.

[0045] Figure 1. Overview of electrochemical synthesis of 2-methyltetrahydrofuran and 1,4- pentanediol from levulinic acid derived esters and gamma-valerolactone.

[0046] DETAILED DESCRIPTION

[0047] The compositions, devices, methods, and systems described herein may be understood more readily by reference to the following detailed description of specific aspects of the disclosed subject matter and the Examples included therein.

[0048] Before the present compositions, devices, methods, and systems are disclosed and described, it is to be understood that the aspects described below are not limited to specific synthetic methods or specific reagents, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only and is not intended to be limiting.

[0049] Also, throughout this specification, various publications are referenced. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which the disclosed matter pertains. The references disclosed are also individually and specifically incorporated by reference herein for the material contained in them that is discussed in the sentence in which the reference is relied upon.

[0050] General Definitions

[0051] In this specification and in the claims that follow, reference will be made to a number of terms, which shall be defined to have the following meanings.

[0052] Throughout the description and claims of this specification the word “comprise” and other forms of the word, such as “comprising” and “comprises,” means including but not limited to, and is not intended to exclude, for example, other additives, components, integers, or steps.

[0053] As used in the description and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a composition” includes mixtures of two or more such compositions, reference to Attorney Docket No. 11255-037WO1

[0054] CU Ref.: 2025-057

[0055] “an agent” includes mixtures of two or more such agents, reference to “the component” includes mixtures of two or more such components, and the like.

[0056] “Optional” or “optionally” means that the subsequently described event or circumstance can or cannot occur, and that the description includes instances where the event or circumstance occurs and instances where it does not.

[0057] Ranges can be expressed herein as from “about” one particular value, and / or to “about” another particular value. By “about” is meant within 5% of the value, e.g., within 4, 3, 2, or 1% of the value. When such a range is expressed, another aspect includes from the one particular value and / or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another aspect. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint.

[0058] “Exemplary” means “an example of’ and is not intended to convey an indication of a preferred or ideal embodiment. “Such as” is not used in a restrictive sense, but for explanatory purposes.

[0059] It is understood that throughout this specification the identifiers “first” and “second” are used solely to aid in distinguishing the various components and steps of the disclosed subject matter. The identifiers “first” and “second” are not intended to imply any particular order, amount, preference, or importance to the components or steps modified by these terms.

[0060] The term “or combinations thereof’ as used herein refers to all permutations and combinations of the listed items preceding the term. For example, “A, B, C, or combinations thereof’ is intended to include at least one of: A, B, C, AB, AC, BC, or ABC, and if order is important in a particular context, also BA, CA, CB, CBA, BCA, ACB, BAC, or CAB. Continuing with this example, expressly included are combinations that contain repeats of one or more item or term, such as BB, AAA, AB, BBC, AAABCCCC, CBBAAA, CAB ABB, and so forth. The skilled artisan will understand that typically there is no limit on the number of items or terms in any combination, unless otherwise apparent from the context.

[0061] The expressions “ambient temperature” and “room temperature” as used herein are understood in the art and refer generally to a temperature from 20°C to 35°C.

[0062] Unless stated to the contrary, a formula with chemical bonds shown only as solid lines and not as wedges or dashed lines contemplates each possible stereoisomer or mixture of stereoisomer (e.g., each enantiomer, each diastereomer, each meso compound, a racemic mixture, or scalemic mixture). Attorney Docket No. 11255-037WO1

[0063] CU Ref.: 2025-057

[0064] Methods

[0065] Provided herein are methods for preparing 2-methyltetrahydrofuran (MTHF), 1,4- pentanediol (PDOL), or a combination thereof from hydroxyvaleric acid. These methods can comprise esterifying the hydroxyvaleric acid to form gamma-valerolactone; contacting a solution of the gamma-valerolactone with a second anode and a second cathode in a second electrochemical cell; and electrochemically reducing the gamma-valerolactone at the second cathode to form the MTHF, PDOL, or a combination thereof.

[0066] In some embodiments, esterifying the hydroxy valeric acid to form gamma-valerolactone comprises an acid-catalyzed esterification.

[0067] In some embodiments, electrochemically reducing the gamma-valerolactone at the second cathode to form the MTHF, PDOL, or a combination thereof produces MTHF as a major (primary) product. In some embodiments, the solution of the gamma-valerolactone has a pH of from 1 to 8, such as from 1 to 7, from 1 to 6, from 1 to 5, from 1 to 4, from 2 to 8, from 2 to 7, from 2 to 6, from 2 to 5, or from 2 to 4. In some embodiments, the solution of the gamma- valerolactone comprises an aqueous solution comprising water, gamma-valerolactone, and one or more electrolytes. In some embodiments, the second anode, the second cathode, or a combination thereof comprise copper or a platinum group metal.

[0068] In other embodiments, electrochemically reducing the gamma-valerolactone at the second cathode to form the MTHF, PDOL, or a combination thereof produces PDOL as a major (primary) product. In some embodiments, the solution of the gamma-valerolactone has a pH of from 7 to 14, such as from 8 to 14, from 9 to 14, from 10 to 14, from 11 to 14, from 7 to 12, such as from 8 to 12, from 9 to 12, from 10 to 12, or from 11 to 12. In some embodiments, the solution of the gamma-valerolactone comprises an aqueous solution comprising water, gamma- valerolactone, and one or more electrolytes. In some embodiments, the second anode, the second cathode, or a combination thereof comprise copper or a platinum group metal.

[0069] In some embodiments, the method further comprises contacting a solution of levulinic acid with a first anode and a first cathode in a first electrochemical cell; and electrochemically reducing the levulinic acid at the first cathode to form the hydroxyvaleric acid.

[0070] In some embodiments, the method is performed as a one-pot process.

[0071] Also provided herein are methods for preparing 1 ,4-pentanediol (PDOL). These methods can comprise esterifying the hydroxyvaleric acid to form a hydroxyvaleric acid ester; contacting a solution of the hydroxyvaleric acid ester with a second anode and a second cathode in a Attorney Docket No. 11255-037WO1

[0072] CU Ref.: 2025-057 second electrochemical cell; and electrochemically reducing the hydroxyvaleric acid ester at the second cathode to form the PDOL.

[0073] In some embodiments, esterifying the hydroxy valeric acid to form the hydroxy valeric acid ester comprises an acid-catalyzed esterification.

[0074] In some embodiments, the hydroxyvaleric acid ester comprises a hydroxyvaleric acid alkyl ester.

[0075] In some embodiments, the solution of the hydroxyvaleric acid ester further comprises a proton donor, such as ammonia, methanol, ethanol, ethylene glycol, or dimethylurea.

[0076] In some embodiments, the solution of the hydroxyvaleric acid ester further comprises a base, such as 1,3 -dimethylurea, triethanolamine, trimethylamine, triethylamine, Piperidine, 2,2- bipyridine, N-methylphthalimide, or N,N-diisopropylethylamine.

[0077] In some embodiments, the solution of the hydroxyvaleric acid ester further comprises a solvent, such as an organic solvent (e.g., THF).

[0078] In some embodiments, the method further comprises contacting a solution of levulinic acid with a first anode and a first cathode in a first electrochemical cell; and electrochemically reducing the levulinic acid at the first cathode to form the hydroxyvaleric acid.

[0079] In some embodiments, the method is performed as a one-pot process.

[0080] Also provided herein are methods for preparing 1 ,4-pentanediol (PDOL). These methods can comprise esterifying levulinic acid to from a levulinic acid ester; contacting a solution of the levulinic acid ester with a first anode and a first cathode in a second electrochemical cell; electrochemically reducing the levulinic acid ester at the first cathode to form a hydroxyvaleric acid ester; contacting a solution of the hydroxyvaleric acid ester with a second anode and a second cathode in a second electrochemical cell; and electrochemically reducing the hydroxyvaleric acid ester at the second cathode to form the PDOL.

[0081] In some embodiments, esterifying the levulinic acid to form the levulinic acid ester comprises an acid-catalyzed esterification.

[0082] In some embodiments, the levulinic acid ester comprises a levulinic acid alkyl ester.

[0083] In some embodiments, the solution of the hydroxyvaleric acid ester further comprises a proton donor, such as ammonia, methanol, ethanol, ethylene glycol, or dimethylurea.

[0084] In some embodiments, the solution of the hydroxyvaleric acid ester further comprises a base, such as 1,3 -dimethylurea, triethanolamine, trimethylamine, triethylamine, Piperidine, 2,2- bipyridine, N-methylphthalimide, or N,N-diisopropylethylamine. Attorney Docket No. 11255-037WO1

[0085] CU Ref.: 2025-057

[0086] In some embodiments, the solution of the hydroxyvaleric acid ester further comprises a solvent, such as an organic solvent (e.g., THF).

[0087] In some embodiments, the method is performed as a one-pot process.

[0088] Methods of Preparing HVA

[0089] Methods for electrochemically obtaining HVA and salts or esters thereof from levulinic acid are described in U.S. Patent Application Publication No. 2024 / 0158926, which is incorporated by reference in its entirety.

[0090] The electrochemical synthesis of hydroxyvaleric acid from levulinic acid can be conducted in an electrochemical cell wherein a working electrode is in electrochemical contact with an aqueous electrolyte and levulinic acid, wherein the method comprises applying a potential to electrochemically reduce the levulinic acid to form hydroxyvaleric acid.

[0091] In some examples, the electrochemical cell comprises a cathodic compartment and an anodic compartment separated by an ion exchange membrane (e.g., a proton exchange membrane, an anion exchange membrane, etc.). In some examples, the electrochemical cell comprises a three-electrode H-type cell, the three-electrodes being the working electrode, a reference electrode, and an auxiliary electrode.

[0092] The working electrode can comprise any suitable electrode, such as those known in the art. For example, the working electrode can comprise an electrically conductive material. In some examples, the working electrode can comprise a metal. In some examples, the working electrode can comprise a metal selected from the group consisting of Be, Mg, Al, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga, Sr, Y, Zr, Nb, Mo, Tc, Ru, Rh, Pd, Ag, Cd, In, Sn, Ba, Hf, Ta, W, Re, Os, Ir, Pt, Au, Hg, Tl, Pb, Bi, La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and combinations thereof. In some examples, the working electrode can comprise a metal selected from the group consisting of Bi, Al, Ti, Fe, Ni, Cu, Zn, Ga, Ag, Cd, In, Sn, Hg, Sb, Pb, and combinations thereof. In some examples, the working electrode comprises Pb, Sn, In, Bi, Cd, Zn, Sb, or a combination thereof. In some examples, the working electrode comprises Pb.

[0093] The aqueous electrolyte can comprise any suitable electrolyte, such as those known in the art. In some examples, the aqueous electrolyte can comprise an inorganic salt such as a metal hydroxide, phosphoric acid, sulfuric acid, or a combination thereof dissolved in water. In some examples, the aqueous electrolyte can comprise a lithium salt, a potassium salt, a sodium salt, a cesium salt, phosphoric acid, sulfuric acid, perchloric acid, or a combination thereof dissolved in water. In some examples, the aqueous electrolyte can comprise water and H2SO4, KCIO4, Attorney Docket No. 11255-037WO1

[0094] CU Ref.: 2025-057

[0095] HCIO4, potassium acetate buffer, KHCO3, K2CO3, KOH, L1HCO3, LiC104, NaHCO3, NaC104, CSHCO3, CsC104, or a combination thereof.

[0096] In some examples, the aqueous electrolyte can have a pH of 0 or more (e.g., 0.5 or more, 1 or more, 1.5 or more, 2 or more, 2.5 or more, 3 or more, 3.5 or more, 4 or more, 4.5 or more, 5 or more, 5.5 or more, 6 or more, 6.5 or more, 7 or more, 7.5 or more, 8 or more, 8.5 or more, 9 or more, 9.5 or more, 10 or more, 10.5 or more, 11 or more, 11.5 or more, 12 or more, 12.5 or more, or 13 or more). In some examples, the aqueous electrolyte can have a pH or 14 or less (e.g., 13.5 or less, 13 or less, 12.5 or less, 12 or less, 11.5 or less, 11 or less, 10.5 or less, 10 or less, 9.5 or less, 9 or less, 8.5 or less, 8 or less, 7.5 or less, 7 or less, 6.5 or less, 6 or less, 5.5 or less, 5 or less, 4.5 or less, 4 or less, 3.5 or less, 3 or less, 2.5 or less, 2 or less, 1.5 or less, or 1 or less). The pH of the aqueous electrolyte can range from any of the minimum values described above to any of the maximum values described above. For example, the aqueous electrolyte can have a pH of from 0 to 14 (e.g., from 0 to 7, from 7 to 14, from 0 to 3, from 3 to 6, from 6 to 9, from 9 to 14, from 0 to 12, from 0 to 10, from 3 to 14, from 5 to 14, from 7 to 14, from 3 to 12, from 5 to 12, from 3 to 10, or from 5 to 10). In some examples, the aqueous electrolyte can have a pH of 3 or more, In some examples, the aqueous electrolyte can have a pH of from 3 to 14. In some examples, the aqueous electrolyte can have a pH of from 5 to 10.

[0097] In some examples, the working electrode comprises Pb, Sn, In, Bi, Cd, Zn, Sb, or a combination thereof and the aqueous electrolyte has a pH of from 3 to 14. In some examples, the working electrode comprises Pb and the aqueous electrolyte has a pH of from 3 to 14.

[0098] In some examples, the working electrode comprises Pb, Sn, In, Bi, Cd, Zn, Sb, or a combination thereof and the aqueous electrolyte has a pH of from 5 to 10. In some examples, the working electrode comprises Pb the aqueous electrolyte has a pH of from 5 to 10.

[0099] In some examples, the method is conducted at a temperature of above freezing of the aqueous electrolyte (e.g., 0°C or more, 5°C or more, 10°C or more, 15°C or more, 20°C or more, 25°C or more, 30°C or more, 35°C or more, 40°C or more, 45°C or more, 50°C or more, 55°C or more, 60°C or more, 65°C or more, 70°C or more, 75°C or more, 80°C or more, 85°C or more, 90°C or more, 95°C or more, 100°C or more, 105°C or more, 110°C or more, or 115°C or more). In some examples, the method is conducted at a temperature of below boiling of the aqueous electrolyte (e.g., 120°C or less, 115°C or less, 110°C or less, 105 °C or less, 100°C or less, 95°C or less, 90°C or less, 85°C or less, 80°C or less, 75°C or less, 70°C or less, 65°C or less, 60°C or less, 55°C or less, 50°C or less, 45°C or less, 40°C or less, 35°C or less, 30°C or less, 25°C or less, 20°C or less, 15°C or less, 10°C or less, or 5°C or less). The temperature at which the Attorney Docket No. 11255-037WO1

[0100] CU Ref.: 2025-057 method is conducted can range from any of the minimum values described above from any of the maximum values described above. For example, the method can be conducted at a temperature of from above freezing to below boiling of the aqueous electrolyte (e.g., from 0°C to 120°C, from 0°C to 60°C, from 60°C to 120°C, from 0°C to 40°C, from 40°C to 80°C, from 80°C to 120°C, from 0°C to 100°C, from 0°C to 80°C, from 0°C to 50°C, from 5°C to 120°C, from 10°C to 120°C, from 20°C to 120°C, from 40°C to 120°C, from 60°C to 120°C, from 5°C to 100°C, from 10°C to 80°C, or from 20°C to 50°C).

[0101] In some examples, the working electrode comprises Pb, Sn, In, Bi, Cd, Zn, Sb, or a combination thereof and the method is conducted at a temperature of from 0°C to 100°C. In some examples, the working electrode comprises Pb and the method is conducted at a temperature of from 0°C to 100°C.

[0102] In some examples, the working electrode comprises Pb, Sn, In, Bi, Cd, Zn, Sb, or a combination thereof and the method is conducted at a temperature from 20°C to 50°C. In some examples, the working electrode comprises Pb and the method is conducted at a temperature from 20°C to 50°C.

[0103] In some examples, the aqueous electrolyte has a pH of from 3 to 14 and the method is conducted at a temperature of from 0°C to 100°C. In some examples, the aqueous electrolyte has a pH of from 5 to 10 and the method is conducted at a temperature of from 0°C to 100°C.

[0104] In some examples, the aqueous electrolyte has a pH of from 3 to 14 and the method is conducted at a temperature from 20°C to 50°C. In some examples, the aqueous electrolyte has a pH of from 5 to 10 and the method is conducted at a temperature from 20°C to 50°C.

[0105] In some examples, the working electrode comprises Pb, Sn, In, Bi, Cd, Zn, Sb, or a combination thereof, the aqueous electrolyte has a pH of from 3 to 14, and the method is conducted at a temperature of from 0°C to 100°C. In some examples, the working electrode comprises Pb, the aqueous electrolyte has a pH of from 3 to 14, and the method is conducted at a temperature of from 0°C to 100°C.

[0106] In some examples, the working electrode comprises Pb, Sn, In, Bi, Cd, Zn, Sb, or a combination thereof, the aqueous electrolyte has a pH of from 5 to 10, and the method is conducted at a temperature from 20°C to 50°C. In some examples, the working electrode comprises Pb the aqueous electrolyte has a pH of from 5 to 10, and the method is conducted at a temperature from 20°C to 50°C.

[0107] In some examples, the levulinic acid has an initial concentration of greater than 0 mol / L (e.g., 0.001 mol / L or more, 0.05 mol / L or more, 0.1 mol / L or more, 0.15 mol / L or more, 0.2 Attorney Docket No. 11255-037WO1

[0108] CU Ref.: 2025-057 mol / L or more, 0.25 mol / L or more, 0.3 mol / L or more, or 0.35 mol / L or more). In some examples, the levulinic acid has an initial concentration of below the solubility limit (e.g., 0.4 mol / L or less, 0.35 mol / L or less, 0.3 mol / L or less, 0.25 mol / L or less, 0.2 mol / L or less, 0.15 mol / L or less, 0.1 mol / L or less, 0.05 mol / L or less, or 0.001 mol / L or less). The initial concentration of the levulinic acid can range from any of the minimum values described above to any of the maximum values described above. For example, the levulinic acid can have an initial concentration from greater than 0 to below the solubility limit (e.g., from greater than 0 to 0.4 mol / L, from greater than 0 to 0.2 mol / L, from 0.2 to 0.4 mol / L, from 0.001 to 0.4 mol / L, from 0.1 to 0.4 mol / L, or from 0.15 to 0.4 mol / L).

[0109] In some examples, the aqueous electrolyte can further comprise an additive, a solvent, or a combination thereof.

[0110] In some examples, the potential applied can be -1.1 V vs. RHE or less (e.g., -1.2 V or less, -1.3 V or less, -1.4 V or less, -1.5 V or less, -1.6 V or less, -1.7 V or less, or -1.8 V or less). In some examples, the potential applied can be -1.9 V vs. RHE or more (e.g., -1.8 V or more, -1.7 V or more, -1.6 V or more, -1.5 V or more, -1.4 V or more, -1.3 V or more, or -1.2 V or more). The potential applied can range from any of the minimum values described above to any of the maximum values described above. For example, the potential can be from -1.1 to -1.9 V vs. RHE (e.g. from -1.1 V to -1.5 V, from -1.5 V to -1.9 V, from -1.1 V to -1.3 V, from -1.3 V to -1.6 V, from -1.6 V to -1.9 V, from -1.2 V to -1.9 V, or from -1.3 V to -1.9 V).

[0111] In some examples, the potential is applied for an amount of time of 1 minute or more (e.g., 2 minutes or more, 3 minutes or more, 4 minutes or more, 5 minutes or more, 6 minutes or more, 7 minutes or more, 8 minutes or more, 9 minutes or more, 10 minutes or more, 15 minutes or more, 20 minutes or more, 25 minutes or more, 30 minutes or more, 35 minutes or more, 40 minutes or more, 45 minutes or more, 50 minutes or more, 55 minutes or more, 60 minutes or more, 70 minutes or more, 80 minutes or more, 90 minutes or more, 100 minutes or more, 110 minutes or more, 120 minutes or more, 150 minutes or more, 180 minutes or more, 210 minutes or more, 240 minutes or more, 270 minutes or more, 300 minutes or more, 330 minutes or more, 360 minutes or more, 390 minutes or more, 420 minutes or more, 450 minutes or more, 480 minutes or more, 540 minutes or more, 600 minutes or more, 660 minutes or more, 720 minutes or more, 780 minutes or more, 840 minutes or more, or 900 minutes or more). In some examples, the potential is applied for an amount of time of 1000 minutes or less (e.g., 900 minutes or less, 840 minutes or less, 780 minutes or less, 720 minutes or less, 660 minutes or less, 600 minutes or less, 540 minutes or less, 480 minutes or less, 450 minutes or less, 420 Attorney Docket No. 11255-037WO1

[0112] CU Ref.: 2025-057 minutes or less, 390 minutes or less, 360 minutes or less, 330 minutes or less, 300 minutes or less, 270 minutes or less, 240 minutes or less, 210 minutes or less, 180 minutes or less, 150 minutes or less, 120 minutes or less, 110 minutes or less, 100 minutes or less, 90 minutes or less, 80 minutes or less, 70 minutes or less, 60 minutes or less, 55 minutes or less, 50 minutes or less, 45 minutes or less, 40 minutes or less, 35 minutes or less, 30 minutes or less, 25 minutes or less, 20 minutes or less, 15 minutes or less, 10 minutes or less, 9 minutes or less, 8 minutes or less, 7 minutes or less, 6 minutes or less, 5 minutes or less, 4 minutes or less, 3 minutes or less, or 2 minutes or less). The amount of time for which the potential is applied can range from any of the minimum values described above to any of the maximum values described above. For example, the potential can be applied for an amount of time of from 1 to 1000 minutes (e.g., from 1 to 500 minutes, from 500 to 1000 minutes, from 1 to 200 minutes, from 200 to 400 minutes, from 400 to 600 minutes, from 600 to 800 minutes, from 800 to 1000 minutes, from 1 to 800 minutes, from 1 to 600 minutes, from 1 to 400 minutes, from 1 to 100 minutes, from 1 to 60 minutes, from 1 to 30 minutes, from 1 to 10 minutes, from 5 to 1000 minutes, from 10 to 1000 minutes, from 30 to 1000 minutes, from 60 to 1000 minutes, from 100 to 1000 minutes, from 200 to 1000 minutes, from 400 to 1000 minutes, from 600 to 1000 minutes, from 5 to 900 minutes, or from 10 to 400 minutes). In some examples, the potential can be applied for an amount of time of from 10 to 400 minutes.

[0113] In some examples, the method further comprises applying a current density. For example, the method can further comprise applying a current density of 1 mA cm'2or more (e.g., 2 mA cm'2or more, 3 mA cm'2or more, 4 mA cm'2or more, 5 mA cm'2or more, 6 mA cm'2or more, 7 mA cm'2or more, 8 mA cm'2or more, 9 mA cm'2or more, 10 mA cm'2or more, 15 mA cm'2or more, 20 mA cm'2or more, 25 mA cm'2or more, 30 mA cm'2or more, 35 mA cm'2or more, 40 mA cm'2or more, 45 mA cm'2or more, 50 mA cm'2or more, 60 mA cm'2or more, 70 mA cm'2or more, 80 mA cm'2or more, 90 mA cm'2or more, 100 mA cm'2or more, 125 mA cm'2or more, 150 mA cm'2or more, 175 mA cm'2or more, 200 mA cm'2or more, 225 mA cm'2or more, 250 mA cm'2or more, 300 mA cm'2or more, 350 mA cm'2or more, 400 mA cm'2or more, 450 mA cm'2or more, 500 mA cm'2or more, 600 mA cm'2or more, 700 mA cm'2or more, 800 mA cm'2or more, 900 mA cm'2or more, 1000 mA cm'2or more, 1250 mA cm'2or more, 1500 mA cm'2or more, or 1750 mA cm'2or more). In some examples, the method can further comprise applying a current density of 2000 mA cm'2or less (e.g., 1750 mA cm'2or less, 1500 mA cm'2or less, 1250 mA cm'2or less, 1000 mA cm'2or less, 900 mA cm'2or less, 800 mA cm'2or less, 700 mA cm'2or less, 600 mA cm'2or less, 500 mA cm'2or less, 450 mA cm'2 Attorney Docket No. 11255-037WO1

[0114] CU Ref.: 2025-057 or less, 400 mA cm'2or less, 350 mA cm'2or less, 300 mA cm'2or less, 250 mA cm'2or less, 225 mA cm'2or less, 200 mA cm'2or less, 175 mA cm'2or less, 150 mA cm'2or less, 125 mA cm'2or less, 100 mA cm'2or less, 90 mA cm'2or less, 80 mA cm'2or less, 70 mA cm'2or less, 60 mA cm'2or less, 50 mA cm'2or less, 45 mA cm'2or less, 40 mA cm'2or less, 35 mA cm'2or less, 30 mA cm'2or less, 25 mA cm'2or less, 20 mA cm'2or less, 15 mA cm'2or less, 10 mA cm'2or less, 9 mA cm'2or less, 8 mA cm'2or less, 7 mA cm'2or less, 6 mA cm'2or less, 5 mA cm'2or less, 4 mA cm'2or less, 3 mA cm'2or less, or 2 mA cm'2or less). The current density applied can range from any of the minimum values described above to any of the maximum values described above. For example, the method can further comprise applying a current density of from 1 to 2000 mA cm'2(e.g., from 1 to 1000 mA cm'2, from 1000 to 2000 mA cm'2, from 1 to 500 mA cm'2, from 500 to 1000 mA cm'2, from 1000 to 1500 mA cm'2, from 1500 to 2000 mA cm'2, from 1 to 1750 mA cm'2, from 1 to 1500 mA cm'2, from 1 to 1250 mA cm'2, from 1 to 750 mA cm'2, from 1 to 250 mA cm'2, from 1 to 100 mA cm'2, from 1 to 50 mA cm'2, from 5 to 2000 mA cm'2, from 10 to 2000 mA cm'2, from 50 to 2000 mA cm'2, from 100 to 2000 mA cm'2, from 250 to 2000 mA cm'2, from 500 to 2000 mA cm'2, from 750 to 2000 mA cm'2, from 1250 to 2000 mA cm'2, from 5 to 1750 mA cm'2, from 10 to 1500 mA cm'2, or from 10 to 205 mA cm'2). In some examples, the method can further comprise applying a current density of from 10 to 205 mA cm'2.

[0115] In some examples, the methods can further comprise agitating the aqueous electrolyte. Agitating the aqueous electrolyte can be accomplished, for example, by mechanical stirring, shaking, vortexing, sonication (e.g., bath sonication, probe sonication, ultrasonication), and the like, or combinations thereof.

[0116] In some examples, the method produces the hydroxyvaleric acid from the levulinic acid with a selectivity of 50% or more (e.g., 55% or more, 60% or more, 65% or more, 70% or more, 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, or 99% or more). In some examples, the method produces the hydroxy valeric acid from the levulinic acid with a selectivity of 100% or less (e.g., 95% or less, 90% or less, 85% or less, 80% or less, 75% or less, 70% or less, 65% or less, 60% or less, or 55% or less). The selectivity with which the method produces the hydroxyvaleric acid can range from any of the minimum values described above to any of the maximum values described above. For example, the method can produce the hydroxyvaleric acid from the levulinic acid with a selectivity of from 50% to 100% (e.g., from 50% to 75%, from 75% to 100%, from 50% to 60%, from 60% to 70%, from 70% to 80%, from Attorney Docket No. 11255-037WO1

[0117] CU Ref.: 2025-057

[0118] 80% to 90%, from 90% to 100%, from 60% to 100%, from 70% to 100%, from 80% to 100%, from 95% to 100%, or from 99% to 100%).

[0119] In some examples, the method produces the hydroxyvaleric acid from the levulinic acid with a Faradaic efficiency of 50% or more (e.g., 55% or more, 60% or more, 65% or more, 70% or more, 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, or 99% or more). In some examples, the method produces the hydroxy valeric acid from the levulinic acid with a Faradaic efficiency of 100% or less (e.g., 95% or less, 90% or less, 85% or less, 80% or less, 75% or less, 70% or less, 65% or less, 60% or less, or 55% or less). The Faradaic efficiency with which the method produces the hydroxyvaleric acid can range from any of the minimum values described above to any of the maximum values described above. For example, the method can produce the hydroxyvaleric acid from the levulinic acid with a Faradaic efficiency of from 50% to 100% (e.g., from 50% to 75%, from 75% to 100%, from 50% to 60%, from 60% to 70%, from 70% to 80%, from 80% to 90%, from 90% to 100%, from 60% to 100%, from 70% to 100%, or from 80% to 100%).

[0120] In some examples, the method converts greater than 0% of the levulinic acid to the hydroxyvaleric acid (e.g., 1% or more, 5% or more, 10% or more, 15% or more, 20% or more, 25% or more, 30% or more, 35% or more, 40% or more, 45% or more, 50% or more, 55% or more, 60% or more, 65% or more, 70% or more, 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, or 99% or more). In some examples, the method converts 100% or less of the levulinic acid to the hydroxyvaleric acid (e.g., 95% or less, 90% or less, 85% or less, 80% or less, 75% or less, 70% or less, 65% or less, 60% or less, 55% or less, 50% or less, 45% or less, 40% or less, 35% or less, 30% or less, 25% or less, 20% or less, 15% or less, 10% or less, or 5% or less). The amount of levulinic acid converted to the hydroxyvaleric acid can range from any of the minimum values described above to any of the maximum values described above. For example, the method can convert from greater than 0 to 100% of the levulinic acid to the hydroxyvaleric acid (e.g., from 5% to 100%, from 10% to 100%, from 20% to 100%, from 25% to 100%, from 50% to 100%, from 60% to 100%, from 70% to 100%, or from 80% to 100%).

[0121] In some examples, the method produces the hydroxyvaleric acid from the levulinic acid at a production rate of 5 g L-1h-1or more (e.g., 10 g L-1h-1or more, 15 g L-1h-1or more, 20 g L-1h-1or more, 25 g L-1h-1or more, 30 g L-1h-1or more, 35 g L-1h-1or more, 40 g L-1h-1or more, 45 g L-1h-1or more, 50 g L-1h-1or more, 60 g L-1h-1or more, 70 g L-1h-1or more, 80 g L-1h-1or more, 90 g L-1h-1or more, 100 g L-1h-1or more, 125 g L-1h-1or more, 150 g L-1h-1or more, 175 g L-1h-1or more, 200 g L-1h-1or more, 225 g L-1h-1or more, 250 g L-1h-1or more, 300 g L" Attorney Docket No. 11255-037WO1

[0122] CU Ref.: 2025-057

[0123] 1h-1or more, 350 g L-1h-1or more, 400 g L-1h-1or more, 450 g L-1h-1or more, 500 g L-1h-1or more, 600 g L-1h-1or more, 700 g L-1h-1or more, 800 g L-1h-1or more, or 900 g L-1h-1or more). In some examples, the method produces the hydroxy valeric acid from the levulinic acid at a production rate of 1000 g L-1h-1or less (e.g., 900 g L-1h-1or less, 800 g L-1h-1or less, 700 g L-1h-1or less, 600 g L-1h-1or less, 500 g L-1h-1or less, 450 g L-1h-1or less, 400 g L-1h-1or less, 350 g L-1h-1or less, 300 g L-1h-1or less, 250 g L-1h-1or less, 225 g L-1h-1or less, 200 g L-1h-1or less, 175 g L-1h-1or less, 150 g L-1h-1or less, 125 g L-1h-1or less, 100 g L-1h-1or less, 90 g

[0124] L-1h-1or less, 80 g L-1h-1or less, 70 g L-1h-1or less, 60 g L-1h-1or less, 50 g L-1h-1or less, 45 g

[0125] L-1h-1or less, 40 g L-1h-1or less, 35 g L-1h-1or less, 30 g L-1h-1or less, 25 g L-1h-1or less, 20 g

[0126] L-1h-1or less, 15 g L-1h-1or less, or 10 g L-1h-1or less). The production rate can range from any of the minimum values described above to any of the maximum values described above. For example, the method can produce the hydroxyvaleric acid from the levulinic acid at a production rate of from 5 to 1000 g L-1h-1(e.g., from 5 to 500 g L-1h1, from 500 to 1000 g L-1h1, from 5 to 200 g L-1h1, from 200 to 400 g L-1h1, from 400 to 600 g L-1h1, from 600 to 800 g L-1h1, from 800 to 1000 g L-1h1, from 5 to 800 g L-1h1, from 5 to 600 g L-1h1, from 5 to 400 g L-1h1, from 5 to 100 g L-1h1, from 5 to 50 g L-1h1, from 5 to 25 g L-1h1, from 10 to 1000 g L-1h1, from 25 to 1000 g L-1h1, from 50 to 1000 g L-1h1, from 100 to 1000 g L-1h1, from 200 to 1000 g L-1h1, from 400 to 1000 g L-1h1, from 600 to 1000 g L-1h1, from 10 to 900 g L-1h1, or from 20 to 800 g L-1h1). In some examples, the method produces the hydroxyvaleric acid from the levulinic acid at a production rate of from 5 to 50 g L-1h1.

[0127] If desired, valeric acid, gamma-valerolactone, or a combination thereof can be synthesized from the levulinic acid. In some examples, the method is a one-pot method.

[0128] Also described herein are methods of synthesizing gamma-valerolactone from hydroxyvaleric acid. For example, the methods described herein can further comprise subsequently converting the electrochemically synthesized hydroxyvaleric acid to gamma- valerolactone. In some examples, the methods can comprise direct aqueous electrochemical conversion of the hydroxyvaleric acid to gamma-valerolactone. In some examples, the methods can comprise electrolysis of the levulinic acid followed by acid-catalyzed esterification to form the gamma-valerolactone. In some examples, the methods can comprise, after synthesizing the hydroxyvaleric acid, adding 30 pL of H2SO4 per mL of electrolyte to initiate acid-catalyzed esterification. In some examples, the method is a one-pot method.

[0129] In some examples, the method converts greater than 0% of the hydroxyvaleric acid to the gamma-valerolactone (e.g., 1% or more, 5% or more, 10% or more, 15% or more, 20% or more, Attorney Docket No. 11255-037WO1

[0130] CU Ref.: 2025-057

[0131] 25% or more, 30% or more, 35% or more, 40% or more, 45% or more, 50% or more, 55% or more, 60% or more, 65% or more, 70% or more, 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, or 99% or more). In some examples, the method converts 100% or less of the hydroxyvaleric acid to the gamma-valerolactone (e.g., 95% or less, 90% or less, 85% or less, 80% or less, 75% or less, 70% or less, 65% or less, 60% or less, 55% or less, 50% or less, 45% or less, 40% or less, 35% or less, 30% or less, 25% or less, 20% or less, 15% or less, 10% or less, or 5% or less). The amount of hydroxyvaleric acid converted to the gamma-valerolactone can range from any of the minimum values described above to any of the maximum values described above. For example, the method can convert from greater than 0 to 100% of the hydroxyvaleric acid to the gamma-valerolactone (e.g., from 5% to 100%, from 10% to 100%, from 20% to 100%, from 25% to 100%, from 50% to 100%, from 60% to 100%, from 70% to 100%, from 80% to 100%, from 90% to 100%, or from 95% to 100%).

[0132] In some examples, the method produces the gamma-valerolactone from the hydroxyvaleric acid with a selectivity of 50% or more (e.g., 55% or more, 60% or more, 65% or more, 70% or more, 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, or 99% or more). In some examples, the method produces the gamma-valerolactone from the hydroxyvaleric acid with a selectivity of 100% or less (e.g., 95% or less, 90% or less, 85% or less, 80% or less, 75% or less, 70% or less, 65% or less, 60% or less, or 55% or less). The selectivity with which the method produces the gamma-valerolactone from the hydroxyvaleric acid can range from any of the minimum values described above to any of the maximum values described above. For example, the method can produce the gamma-valerolactone from the hydroxyvaleric acid with a selectivity of from 50% to 100% (e.g., from 50% to 75%, from 75% to 100%, from 50% to 60%, from 60% to 70%, from 70% to 80%, from 80% to 90%, from 90% to 100%, from 60% to 100%, from 70% to 100%, from 80% to 100%, from 95% to 100%, or from 99% to 100%).

[0133] In some examples, the method produces the gamma-valerolactone from the hydroxyvaleric acid with a yield of 50% or more (e.g., 55% or more, 60% or more, 65% or more, 70% or more, 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, or 99% or more). In some examples, the method produces the gamma-valerolactone from the hydroxyvaleric acid with a yield of 100% or less (e.g., 95% or less, 90% or less, 85% or less, 80% or less, 75% or less, 70% or less, 65% or less, 60% or less, or 55% or less). The yield with which the method produces the gamma-valerolactone from the hydroxyvaleric acid can range from any of the minimum values described above to any of the maximum values described Attorney Docket No. 11255-037WO1

[0134] CU Ref.: 2025-057 above. For example, the method can produce the gamma- valerolactone from the hydroxyvaleric acid with a yield of from 50% to 100% (e.g., from 50% to 75%, from 75% to 100%, from 50% to 60%, from 60% to 70%, from 70% to 80%, from 80% to 90%, from 90% to 100%, from 60% to 100%, from 70% to 100%, from 80% to 100%, or from 90% to 100%).

[0135] In some examples, the method produces the gamma-valerolactone from the hydroxyvaleric acid in an amount of time of 1 minute or more (e.g., 5 minutes or more, 10 minutes or more, 15 minutes or more, 20 minutes or more, 25 minutes or more, 30 minutes or more, 35 minutes or more, 40 minutes or more, 45 minutes or more, 50 minutes or more, 55 minutes or more, 60 minutes or more, 65 minutes or more, 70 minutes or more, 75 minutes or more, 80 minutes or more, 85 minutes or more, 90 minutes or more, 95 minutes or more, 100 minutes or more, 105 minutes or more, 110 minutes or more, or 115 minutes or more). In some examples, In some examples, the method produces the gamma-valerolactone from the hydroxyvaleric acid in an amount of time of 120 minutes or less (e.g., 115 minutes or less, 110 minutes or less, 105 minutes or less, 100 minutes or less, 95 minutes or less, 90 minutes or less, 85 minutes or less, 80 minutes or less, 75 minutes or less, 70 minutes or less, 65 minutes or less, 60 minutes or less, 55 minutes or less, 50 minutes or less, 45 minutes or less, 40 minutes or less, 35 minutes or less, 30 minutes or less, 25 minutes or less, 20 minutes or less, 15 minutes or less, 10 minutes or less, or 5 minutes or less). The amount of time can range from any of the minimum values described above to any of the maximum values described above. For example, the method can produce the gamma-valerolactone from the hydroxyvaleric acid in an amount of time of from 1 to 120 minutes (e.g., from 1 to 60 minutes, from 60 to 120 minutes, from 1 to 30 minutes, from 30 to 60 minutes, from 60 to 90 minutes, from 90 to 120 minutes, from 1 to 100 minutes, from 1 to 80 minutes, from 1 to 40 minutes, from 1 to 20 minutes, from 1 to 10 minutes, from 5 to 120 minutes, from 10 to 120 minutes, from 20 to 120 minutes, from 30 to 120 minutes, from 40 to 120 minutes, from 80 to 120 minutes, from 5 to 100 minutes, from 5 to 60 minutes, or from 5 to 30 minutes). In some examples, the method produces the gamma- valerolactone from the hydroxyvaleric acid in an amount of time of from 5 to 30 minutes.

[0136] A number of embodiments of the invention have been described. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of the invention. Accordingly, other embodiments are within the scope of the following claims.

[0137] The examples below are intended to further illustrate certain aspects of the systems and methods described herein, and are not intended to limit the scope of the claims. Attorney Docket No. 11255-037WO1

[0138] CU Ref.: 2025-057

[0139] EXAMPLES

[0140] The following examples are set forth below to illustrate the methods and results according to the disclosed subject matter. These examples are not intended to be inclusive of all aspects of the subject matter disclosed herein, but rather to illustrate representative methods and results. These examples are not intended to exclude equivalents and variations of the present invention which are apparent to one skilled in the art.

[0141] Efforts have been made to ensure accuracy with respect to numbers (e.g., amounts, temperature, etc.) but some errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, temperature is in °C or is at ambient temperature, and pressure is at or near atmospheric. There are numerous variations and combinations of measurement conditions, e.g., component concentrations, temperatures, pressures and other measurement ranges and conditions that can be used to optimize the described process.

[0142] Example 1. Electrochemical synthesis of 2-methyltetrahydrofuran and 1,4-pentanediol from Levulinic acid derived esters and gamma-valerolactone.

[0143] Summary

[0144] Described herein are electrochemical processes for converting levulinic acid derivatives, hydroxyvaleric acid esters (HVA-esters) and gamma-valerolactone (GVL), into high-value chemicals: 2-Methyltetrahydrofuran (MTHF) and 1 ,4-Pentanediol (PDOL). This strategy can provide sustainable chemistry and bio-based alternatives for industries that traditionally rely on petrochemical derivatives.

[0145] The scope of reactions revolve around the electrochemical conversion pathways for these key bio-based chemicals. These electrochemical methods can offer improved efficiency, selectivity, and sustainability as compared to conventional catalytic or biotransformation processes.

[0146] Reaction Scope and Methodology

[0147] Figure 1 illustrates example electrochemical pathways that can be used to access 2- Methyltetrahydrofuran (MTHF) and 1 ,4-Pentanediol (PDOL). The electrochemical conversion of levulinic acid (LA) to hydroxyvaleric acid (HVA) and to gamma-valerolactone (GVL) (paths 1 and 2) has been described in U.S. Patent Application Publication No. 2024 / 0158926, which is incorporated by reference in its entirety. As described herein, GVL can be further reduced to 2- methyltetrahydrofuran (MTHF) or 1 ,4-pentanediol (PDOL) depending on the pH and some other electrochemical-reaction conditions (paths 3 and 4). Alternatively, LA can be converted into its Attorney Docket No. 11255-037WO1 CU Ref.: 2025-057 ester (e.g., its methyl or ethyl ester) via a conventional esterification reaction, and these esters can then be electrochemically reduced to hydroxyvalerate esters (HVA-ester) (paths 5 and 6). Then, the HVA-ester can be further reduced to PDOL (path 7). HVA can also be converted into an ester by conventional esterification reactions, using alcohol protecting functions — using trialkylsilyl compounds or tetrahydropyranyl (THP) — to eliminate its self-esterification to GVL under these reaction conditions.

[0148] General Electrochemical Reactor Design and Materials

[0149] Batch electrochemical reactors can be designed in cylindrical or H-cell shape, with or without a selective membrane or porous separator. Flow electrochemical reactors can be designed with parallel plates or stacked discs, with divided or undivided cathodic and anodic compartments, using membranes or porous separators. Anion, cation, or bipolar membranes can be used. They have open and gas-tight configurations, with control of gasses inlet and outlet flow, with control of internal pressure. Air, hydrogen, oxygen, argon, and nitrogen can be used as reactants or to remove oxygen from the reactor. Two, three, or four electrode configurations can be utilized (e.g., including working electrodes, counter electrodes, reference electrodes, sensing electrodes). These electrodes can be shaped as plates, cylindrical, C-shaped or cylinders. These electrodes are assembled as static parallel plates, multi-rods, and stacked discs, or they are rotating cylinders. Batch and flow reactors can be used in a single mode — reaction performed in a single reactor from beginning to the end — or combined in series for continuous mode of operation, where the solution of one reactor is moved to a next reactor in line. Multi-reactors operation flow can be composed of two or more reactors. Reaction solutions can be transferred between reactors with pumps in a single pass or recirculating mode. These reactors can also have their temperature controlled via recirculating fluid jackets, cooling fans and Peltier plates. Thermocouples are used to monitor the temperature of the reactor.

[0150] Electrodic materials can be composed by Pb, Sn, Sb, Ti, In, Bi, Cd, Zn, Mg, Al, Ag, Cu, Ni, Pt, Au, Pd, carbon (and allotropes, including boron-doped diamond, graphite, glassy carbon, reticulated vitreous carbon, among others), DSA, as well as alloys and solutions of these elements and their oxides, nitrides, carbides, phosphides, borides.

[0151] Electrode potentials can be set from -1.1 V vs. RHE to cathodic stability limit of the solvents. From -1.1 V vs. RHE to -2V, -5V. The reaction can also be performed at galvanostatic conditions, constant current, applying current density of from 0 to 2 A cm'2, or from 10 to 300 mA cm'2. Pulsed or alternating potential and current modes can also used. The duration of the Attorney Docket No. 11255-037WO1

[0152] CU Ref.: 2025-057 reaction can be related to reaction conversion, for example, the reaction time necessary time to achieve conversion between 10 to 100%.

[0153] General Reaction Conditions

[0154] Reactions can be performed at temperatures from 0 to 100 degrees Celsius, or at higher temperatures under reflux mode using round flask electrochemical reactors.

[0155] Reactions can be performed in water or aqueous mixture, in organic solvents and mixtures of solvents. Aqueous mixtures can be made with co-solvents such as ethanol, methanol, acetonitrile, acetone, propylene carbonate, tetrahydrofuran, dimethyl sulfoxide, and dimethylformamide. These co-solvents can also be used as sacrificial reactants. Co-solvent content can vary from 0 to 50%. Same organic solvents are used pure or intermixed at water-free and very low content of water (<1%) conditions. Solvent-free conditions can also used, gammavalerolactone (GVL) and hydroxy valerate esters (HVA-ester) can only mixed with electrolyte salts to increase conductivity.

[0156] Aqueous electrolytes can have a pH buffered from 0 to 14, while best performances are normally achieved at pH 0, close to neutral, and close to 13. Electrolytes can be inorganic or organic soluble salts, acids, and bases. In some examples, the aqueous electrolytes can be composed of ammonium, Li, K, Na, Cs, Mg, Ca, Al, Zn sats of phosphates, sulfates, chlorides, bromides, iodide, borate, perchlorates, carbonates, bicarbonates, tetrafluoroborate, hexafluorophosphate, and their hydroxides. The concentration of these electrolytes can vary from 0 to 5M, or solubility limit. Organic electrolytes are composed of Li, K, Na salts of hexafluorophosphate, perchlorates, tetrafluoroborate. Tetramethylammonium, Tetraethylammonium, and Tetrabutylammonium of cyanide, methanesulfonate, carbonate, triflate, acetate, chloride, bromide, iodide. The concentration of these electrolytes can vary from 0 to 5M, or solubility limit. Some additives can also beused to prevent fouling of electrodes, as bases or sacrificial reactants, such as 1,3-dimethylurea, triethanolamine, trimethylamine, triethylamine, Piperidine, 2,2-bipyridine, N-methylphthalimide, or N,N-diisopropylethylamine. Ammonia, methanol, ethanol, ethylene glycol, dimethylurea are also used as proton donors; they undergo proton transfer with the intermediates and can also produce sacrificial reactants for the anodic reaction.

[0157] The concentration of precursors (methyl or ethyl hydroxylevulinate, and gammavalerolactone) can vary from greater than zero up to their solubility limit in each solvent or mixtures, at the reaction temperature.

[0158] Reaction Classes Attorney Docket No. 11255-037WO1

[0159] CU Ref.: 2025-057

[0160] Esterification Reactions — Path 2, 5, and 8: Conventional esterification protocols can be used to convert LA and HVA into their respective methyl and ethyl esters. LA and HVA can be reacted with methanol or ethanol, in the presence of an acid catalyst. Sulfuric acid, p- toluenesulfonic acid (PTSA), or acidic ion-exchange resins are used as catalysts. For HVA, esterification leads to GVL, otherwise its hydroxy group is protected with trialkylsilyl compounds or tetrahydropyranyl (THP), or other alcohol protecting agents, to eliminate its conversion to GVL under esterification conditions, producing the HVA-esters. The reaction can be performed at temperatures ranging between 60°C and 100°C under azeotropic distillation. Dean-Stark apparatus can also be employed to continuously remove water from the reaction mixture, ensuring higher yields of the ester.

[0161] Reaction Condition 1 — Path 3 and 4: GVL can be dissolved in aqueous electrolyte. pH is buffered to acidic, neutral or alkaline to shift the reaction selectivity between MTHF and PDOL. Extra proton donors such as ammonia, methanol, ethanol, ethylene glycol, or dimethylurea are added to inhibit the competing hydrogen evolution reaction (HER). Cosolvents can also added to inhibit HER and increase GVL solubility. Some additives can also used to prevent fouling of electrodes and as bases, such as 1,3 -dimethylurea, triethanolamine, trimethylamine, triethylamine, Piperidine, 2,2-bipyridine, N-methylphthalimide, or N,N- diisopropylethylamine.

[0162] Reaction Condition 2 — Path 3 and 4: Electrolyte salts can be dissolved in GVL for solvent-free reaction. Excess equivalent proton donors such as ammonia, methanol, ethanol, ethylene glycol, or dimethylurea can be used. Some additives can also be used to prevent fouling of electrodes and as bases, such as 1,3 -dimethylurea, triethanolamine, trimethylamine, triethylamine, Piperidine, 2,2-bipyridine, N-methylphthalimide, or N,N-diisopropylethylamine.

[0163] Reaction Condition 3 — Path 7: Hydroxyvalerate esters (HVA-ester) can be dissolved in tetrahydrofuran (THF). HVA-ester can be dissolved in organic solvent and mixtures. Excess proton donors such as ammonia, methanol, ethanol, ethylene glycol, or dimethylurea are added. Some additives are also used to prevent fouling of electrodes and as bases, such as 1,3- dimethylurea, triethanolamine, trimethylamine, triethylamine, Piperidine, 2,2-bipyridine, N- methylphthalimide, or N,N-diisopropylethylamine.

[0164] Reaction Condition 4 — Path 7: Electrolyte salts can be dissolved in hydroxy valerate esters (HVA-ester) to increase conductivity. Excess equivalent proton donors such as ammonia, methanol, ethanol, ethylene glycol, or dimethylurea are used. Some additives are also used to prevent fouling of electrodes and as bases, such as 1,3-dimethylurea, triethanolamine, Attorney Docket No. 11255-037WO1 CU Ref.: 2025-057 trimethylamine, triethylamine, Piperidine, 2,2-bipyridine, N-methylphthalimide, or N,N- diisopropylethylamine.

[0165] Other advantages which are obvious and which are inherent to the invention will be evident to one skilled in the art. It will be understood that certain features and sub-combinations are of utility and may be employed without reference to other features and sub-combinations. This is contemplated by and is within the scope of the claims. Since many possible embodiments may be made of the invention without departing from the scope thereof, it is to be understood that all matter herein set forth or shown in the accompanying drawings is to be interpreted as illustrative and not in a limiting sense.

[0166] The methods of the appended claims are not limited in scope by the specific methods described herein, which are intended as illustrations of a few aspects of the claims and any methods that are functionally equivalent are intended to fall within the scope of the claims. Various modifications of the methods in addition to those shown and described herein are intended to fall within the scope of the appended claims. Further, while only certain representative method steps disclosed herein are specifically described, other combinations of the method steps also are intended to fall within the scope of the appended claims, even if not specifically recited. Thus, a combination of steps, elements, components, or constituents may be explicitly mentioned herein or less, however, other combinations of steps, elements, components, and constituents are included, even though not explicitly stated.

Claims

Attorney Docket No. 11255-037WO1CU Ref.: 2025-057CLAIMSWhat is claimed is:

1. A method for preparing 2-methyltetrahydrofuran (MTHF), 1 ,4-pentanediol (PDOL), or a combination thereof from hydroxy valeric acid, the method comprising: esterifying the hydroxyvaleric acid to form gamma-valerolactone; contacting a solution of the gamma-valerolactone with a second anode and a second cathode in a second electrochemical cell; and electrochemically reducing the gamma-valerolactone at the second cathode to form the MTHF, PDOL, or a combination thereof.

2. The method of claim 1, wherein esterifying the hydroxyvaleric acid to form gamma- valerolactone comprises an acid-catalyzed esterification.

3. The method of any one of claims 1-2, wherein electrochemically reducing the gamma- valerolactone at the second cathode to form the MTHF, PDOL, or a combination thereof produces MTHF as a major product.

4. The method of claim 3, wherein the solution of the gamma-valerolactone has a pH of from 1 to 8, such as from 1 to 7, from 1 to 6, from 1 to 5, from 1 to 4, from 2 to 8, from 2 to 7, from 2 to 6, from 2 to 5, or from 2 to 4.

5. The method of any one of claims 3-4, wherein the solution of the gamma-valerolactone comprises an aqueous solution comprising water, gamma-valerolactone, and one or more electrolytes.

6. The method of any one of claims 3-5, wherein the second anode, the second cathode, or a combination thereof comprise copper or a platinum group metal.

7. The method of any one of claims 1-2, wherein electrochemically reducing the gamma- valerolactone at the second cathode to form the MTHF, PDOL, or a combination thereof produces PDOL as a major product.Attorney Docket No. 11255-037WO1CU Ref.: 2025-0578. The method of claim 7, wherein the solution of the gamma-valerolactone has a pH of from 7 to 14, such as from 8 to 14, from 9 to 14, from 10 to 14, from 11 to 14, from 7 to 12, such as from 8 to 12, from 9 to 12, from 10 to 12, or from 11 to 12.

9. The method of any one of claims 7-8, wherein the solution of the gamma-valerolactone comprises an aqueous solution comprising water, gamma-valerolactone, and one or more electrolytes.

10. The method of any one of claims 7-9, wherein the second anode, the second cathode, or a combination thereof comprise copper or a platinum group metal.

11. The method of any one of claims 1-10, wherein the method further comprises contacting a solution of levulinic acid with a first anode and a first cathode in a first electrochemical cell; and electrochemically reducing the levulinic acid at the first cathode to form the hydroxyvaleric acid.

12. The method of any one of claims 1-11, wherein the method is performed as a one-pot process.

13. A method for preparing 1 ,4-pentanediol (PDOL), the method comprising: esterifying the hydroxyvaleric acid to form a hydroxyvaleric acid ester; contacting a solution of the hydroxyvaleric acid ester with a second anode and a second cathode in a second electrochemical cell; and electrochemically reducing the hydroxyvaleric acid ester at the second cathode to form the PDOL.

14. The method of claim 13 wherein esterifying the hydroxy valeric acid to form the hydroxyvaleric acid ester comprises an acid-catalyzed esterification.

15. The method of any one of claims 13-14, wherein the hydroxyvaleric acid ester comprises a hydroxyvaleric acid alkyl ester.Attorney Docket No. 11255-037WO1CU Ref.: 2025-05716. The method of any one of claims 13-15, wherein the solution of the hydroxyvaleric acid ester further comprises a proton donor, such as ammonia, methanol, ethanol, ethylene glycol, or dimethylurea.

17. The method of any one of claims 13-16, wherein the solution of the hydroxyvaleric acid ester further comprises a base, such as 1,3 -dimethylurea, triethanolamine, trimethylamine, triethylamine, Piperidine, 2,2-bipyridine, N-methylphthalimide, or N,N-diisopropylethylamine.

18. The method of any one of claims 13-17, wherein the solution of the hydroxyvaleric acid ester further comprises a solvent, such as an organic solvent (e.g., THF).

19. The method of any one of claims 13-18, wherein the method further comprises contacting a solution of levulinic acid with a first anode and a first cathode in a first electrochemical cell; and electrochemically reducing the levulinic acid at the first cathode to form the hydroxyvaleric acid.

20. The method of any one of claims 13-19, wherein the method is performed as a one-pot process.

21. A method for preparing 1 ,4-pentanediol (PDOL), the method comprising: esterifying levulinic acid to from a levulinic acid ester; contacting a solution of the levulinic acid ester with a first anode and a first cathode in a second electrochemical cell; electrochemically reducing the levulinic acid ester at the first cathode to form a hydroxyvaleric acid ester; contacting a solution of the hydroxyvaleric acid ester with a second anode and a second cathode in a second electrochemical cell; and electrochemically reducing the hydroxyvaleric acid ester at the second cathode to form the PDOL.

22. The method of claim 21 wherein esterifying the levulinic acid to form the levulinic acid ester comprises an acid-catalyzed esterification.Attorney Docket No. 11255-037WO1CU Ref.: 2025-05723. The method of any one of claims 21-22, wherein the levulinic acid ester comprises a levulinic acid alkyl ester.

24. The method of any one of claims 21-23, wherein the solution of the hydroxy valeric acid ester further comprises a proton donor, such as ammonia, methanol, ethanol, ethylene glycol, or dimethylurea.

25. The method of any one of claims 21-24, wherein the solution of the hydroxy valeric acid ester further comprises a base, such as 1,3 -dimethylurea, triethanolamine, trimethylamine, triethylamine, Piperidine, 2,2-bipyridine, N-methylphthalimide, or N,N-diisopropylethylamine.

26. The method of any one of claims 21-25, wherein the solution of the hydroxyvaleric acid ester further comprises a solvent, such as an organic solvent (e.g., THF).

27. The method of any one of claims 21-26, wherein the method is performed as a one-pot process.

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