Purification technique

Abstract

The present invention provides various techniques relating to purification of certain glycol compounds, and more particularly to purification methods when these compounds are present in aqueous compositions, such as fermentation cultures or compositions prepared therefrom, where the fermentation cultures comprise, for example, fermentation cultures that produce or have produced (e.g., glycolic acid, glycolic acid, glycolic acid, glycolic acid, glycolic acid, glycolic acid, glycolic acid, glycolic acid, glycolic acid, glycolic acid, glycolic acid, glycolic acid, etc. Cells (e.g., microbial cells) genetically engineered to produce) related diol compounds.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to U.S. Provisional Application No. 63 / 390,947 filed on July 20, 2022 and U.S. Provisional Application No. 63 / 446,783 filed on February 17, 2023, the entire contents of each of the above applications are incorporated herein by reference. Background Art

[0003] Diol compounds have a variety of uses and applications. Summary of the invention

[0004] The present invention provides various techniques related to the purification of certain diol compounds, particularly techniques for purifying these compounds when they are present in aqueous compositions. In some embodiments, the provided techniques can be used to purify diol compounds from aqueous compositions comprising cells (e.g., microbial cells) and / or components thereof.

[0005] In some embodiments, provided are ion exchange (IEX) techniques. In some embodiments, provided techniques are demonstrated to be able to successfully purify relevant diol compounds from aqueous compositions with less loss of diol compounds due to adsorption to ion exchange resins than appropriate relevant reference processes.

[0006] In some embodiments, provided are filtration techniques. In some embodiments, provided techniques are demonstrated to be successful in separating desired aqueous glycol compound compositions (e.g., compositions that may include cells, such as microbial cells and / or components thereof) from insoluble matter and macromolecular contaminants.

[0007] In some embodiments, the present disclosure provides a combination of technological improvements (eg, filtration techniques and / or ion exchange techniques) that together enable particularly efficient purification of diol compound preparations, particularly from aqueous sources or compositions.

[0008] The present disclosure provides techniques that solve certain problems that may be encountered when attempting to purify diol compounds, particularly when purifying from aqueous compositions. In addition, the present disclosure provides insight that the provided techniques are particularly useful for purifying certain diol compounds described herein (e.g., "long chain" diol compounds, such as fatty alcohol compounds having at least 5 carbon atoms). Moreover, the present disclosure provides insight that the provided techniques are particularly useful when isolating such compounds from aqueous compositions, particularly from compositions having a water content greater than about 50% and / or from compositions comprising cells (e.g., microbial cells) and / or components thereof.

[0009] The present disclosure identifies the source of a particular problem associated with ion exchange purification of diol compounds discussed herein (e.g., fatty alcohol compounds having at least 5 carbon atoms), particularly when purified from aqueous compositions, namely, the degree of retention of the compounds of interest on ion exchange resins. For example, the present disclosure identifies the source of problems that exist with many typical ion exchange techniques when applied to the purification of diol compounds described herein. For example, the present disclosure provides a surprising teaching that better results (e.g., less resin retention) can be obtained by using a hydrophilic resin (e.g., compared to a typical hydrophobic resin such as a polystyrene support).

[0010] Among other things, the present disclosure demonstrates that, surprisingly, pre-masking and / or post-recovery can significantly reduce the loss of diol compounds. In some embodiments, the unexpected reduction can be achieved even with resins whose base polymers are hydrophobic.

[0011] The present disclosure recognizes that resin retention levels may present particular challenges when larger scale fermentation broth volumes (e.g., in the range of about 10 kL to about 1000 kL, or in some embodiments, in the range of about 20 kL to about 80 kL, or even in the range of about 30 kL to about 70 kL) need to be purified. In some embodiments, the provided technology is performed in the scale range of about 10 kL to about 1000 kL.

[0012] The present invention identifies the source of the problems associated with purifying higher order (eg, containing more than 5 carbon atoms, such as 5-12 carbon atoms) diol compounds from aqueous preparations containing other ions and fermentation cell material.

[0013] Among other things, the present invention identifies the challenges faced in separating hydrophilic and hydrophobic substances from each other, particularly in the context of purifying higher order (e.g., containing more than 5 carbon atoms, such as 5-12 carbon atoms) diol compounds from aqueous preparations containing other ions and fermentation cell material.

[0014] Among other aspects, in some embodiments, the present invention provides novel and improved techniques for separating ions from aqueous solutions.

[0015] In some embodiments, the present disclosure provides a diol compound formulation, the manufacture of which includes one or more provided methods. In some embodiments, the present disclosure provides a method for manufacturing a product using such a diol compound formulation. In some embodiments, the product is a polymer. In some embodiments, the product is a solvent. In some embodiments, the product is an acrylate. In some embodiments, the product is a polyurethane. In some embodiments, the product is a polyester. In some embodiments, the product is an adhesive. In some embodiments, the product is a plasticizer.

[0016] In some embodiments, the present disclosure provides a method for characterizing whether a resin is suitable for purifying an initial aqueous formulation containing a diol compound, the method comprising determining whether the particle size, crosslink density, type of functional group, functional group density, and hydrophilicity of the resin are within a suitable or desired range, or whether it has suitable or desired properties. In some embodiments, the present disclosure provides a method for characterizing whether a resin is suitable for purifying an initial aqueous formulation containing a diol compound, the method comprising determining whether the loss of the diol compound is acceptable when the resin is used for ion exchange according to one or more methods and / or schemes described herein. In some embodiments, the present disclosure provides a method for characterizing whether a resin is suitable for purifying an initial aqueous formulation containing a diol compound, the method comprising determining whether the loss of the diol compound is lower than that of a hydrophobic resin when the resin is used for ion exchange under conditions comparable to those of a hydrophobic resin.

[0017] In some embodiments, the present disclosure provides a high purity diol compound preparation. In some embodiments, the present disclosure provides a purified diol compound preparation, wherein the content of each ion and / or impurity is about or at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 500 or 1000 times less than the content in the initial aqueous preparation from which the diol compound is purified.

[0018] In some embodiments, the provided methods include decolorization and / or deodorization. In some embodiments, the provided 1,6-hexanediol (HDO) compositions, such as HDO preparations, are colorless liquids (e.g., HDO solutions). In some embodiments, the provided HDO compositions, such as HDO preparations, are colorless solids. . BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 .A schematic flow chart showing by way of example a useful sequence of processing steps for a diol compound from fermentation to purification.

[0020] definition

[0021] Associated: As used herein, two events or entities are "associated" together if the presence, level, degree, type, and / or form of one is associated with the presence, level, degree, type, and / or form of the other. For example, a particular entity (e.g., a polypeptide, genetic marker, metabolite, microorganism, etc.) is considered to be associated with a particular disease, disorder, or condition if the presence, level, and / or form of the particular entity (e.g., a polypeptide, genetic marker, metabolite, microorganism, etc.) is associated with the incidence, susceptibility, severity, stage, etc. of the disease, disorder, or condition (e.g., in a relevant population). In some embodiments, two or more entities are physically "associated" together if they interact, directly or indirectly, so that they are in and / or remain in physical proximity to each other. In some embodiments, two or more entities that are physically associated with each other are covalently bonded to each other; in some embodiments, two or more entities that are physically associated with each other are not covalently bonded to each other, but are non-covalently associated by means such as hydrogen bonding, van der Waals forces, hydrophobic interactions, magnetic forces, and combinations thereof.

[0022] Comparable: As used herein, the term "comparable" refers to two or more reagents, entities, situations, condition groups, etc., which may not be identical to each other, but are similar enough to allow comparisons between them, so that those skilled in the art can understand that conclusions can be reasonably drawn based on the observed differences or similarities. In some embodiments, comparable condition groups, situations, individuals or groups are characterized by a plurality of substantially identical features and one or a small amount of changes. Those of ordinary skill in the art will understand that in any given case, two or more such reagents, entities, situations, condition groups, etc. are to be considered as comparable required same degrees according to the context. For example, those of ordinary skill in the art will understand that when situation groups, individuals or groups are characterized by sufficient number and type of substantially identical features, to ensure that the results obtained under different situation groups, individuals or groups or using different situation groups, individuals or groups The difference or observed phenomenon is caused by the change of the characteristics of those changes or indicates the change of the characteristics of those changes, then these situation groups, individuals or groups are comparable to each other.

[0023] Crosslinking: As used herein, the terms "crosslinking," "crosslinked," "crosslinking," or grammatical equivalents thereof, refer to the covalent bonding of polymer chains in the backbone of a polymeric support structure. Crosslinking affects many key macroscopic and microscopic parameters of a polymer or resin, including but not limited to particle size, number of equivalents per unit of resin, mechanical strength and resistance to deformation, hydrophilicity and hydrophobicity, number of regeneration cycles, and overall lifespan.

[0024] Equivalents per unit of resin: Those skilled in the art will appreciate that resins are complex mixtures that form a combination of functional and chemical properties. The total number of sites available for ion exchange can be determined before or after the resin is converted to a given ionic form by chemical regeneration techniques (e.g., exchanging chloride ions of an anion exchange resin for hydroxide ions). One ion is then chemically removed from a given amount of resin and quantitatively determined in solution by conventional analytical methods. The total ionic capacity can be expressed on a dry weight, wet weight, wet volume or dry volume basis. The water absorption of the resin, and therefore its wet weight and wet volume capacity, depends on the nature of the polymer support structure and the environment in which the sample is located. The standard way to express the number of charged functional groups available for exchange can be written as eq / L (equivalents per liter) or eq / g (equivalents per gram), including converted forms such as meq / g (milliequivalents per gram).

[0025] Diol compound: As used herein, the term "diol compound" refers to a compound having a L-(OH)n structure, wherein n is 2 or 3, and L is a divalent or trivalent C 2-15 (For example, C2, C3, C4, C5, C6, C7, C8, C9, C 10 ,C 11 ,C 12 ,C 13 ,C 14 or C 15 ) aliphatic moiety. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, L is saturated. In some embodiments, L is unsaturated. In some embodiments, L is linear. In some embodiments, L is branched. In some embodiments, L is C 2-12 In some embodiments, L is C 2-10 In some embodiments, L is C 5-12 In some embodiments, L is C 5-10 Aliphatic moiety. In some embodiments, L is a C5-8 aliphatic moiety. In some embodiments, the diol compound is HO(CH2)2OH. In some embodiments, the diol compound is HO(CH2)3OH. In some embodiments, the diol compound is HO(CH2)4OH. In some embodiments, the diol compound is HO(CH2)5OH. In some embodiments, the diol compound is HO(CH2)6OH. In some embodiments, the diol compound is HO(CH2)7OH. In some embodiments, the diol compound is HO(CH2)8OH. In many embodiments of the diol compound, the hydroxyl groups are attached to different carbon atoms.

[0026] Improve, increase, inhibit or decrease: As used herein, terms such as "improve", "increase", "inhibit", "decrease" or their grammatical equivalents refer to values ​​relative to a baseline or other reference measurement. In some embodiments, a suitable reference measurement may be or include a measurement in a specific system (e.g., in a single individual) under otherwise comparable conditions in the absence of a specific agent or treatment (e.g., before and / or after a specific agent or treatment), or a measurement in the presence of a suitable comparable reference agent. In some embodiments, a suitable reference measurement may be or include a measurement in a comparable system that is known or expected to respond in a specific manner in the presence of a relevant agent or treatment.

[0027] Ion Exchange Resins: Ion exchange is the reversible exchange of ions between a solid (ion exchange resin) and a liquid. Ion exchange resins may include a cross-linked polymer support structure with ion-active sites distributed throughout the structure. Ion exchange resins may have utility in chemical synthesis, fermentation, biocatalysis, medical research, food processing, mining, agriculture, and a variety of other fields.

[0028] Matrix: As used herein, the term "matrix" refers to the properties of a polymer or copolymer derived from a group of monomers (eg, polystyrene is derived from styrene by polymerization). In some embodiments, the polymer matrix is ​​a polymer support structure.

[0029] Particle size: As used herein, the term "particle size" refers to the longest dimension of a particle. In some embodiments, a population of particles is characterized by an average size. In some embodiments, a particle can be substantially spherical (e.g., such that its longest dimension can be its diameter). In some embodiments, an ion exchange resin is characterized by its average particle size; in some embodiments, an ion exchange resin useful according to the present disclosure can have an average particle size (e.g., diameter) in the range of about 100 μm to 1500 μm.

[0030] Porosity: As used herein, the term "porosity" refers to the voids present in or on a resin or matrix (e.g., an ion exchange resin), such as voids in or on particles of such a resin or matrix. In general, the conditions under which a resin or matrix is ​​formed (e.g., the polymerization conditions under which a polymer matrix is ​​formed) determine its porosity. It is known to those skilled in the art that various aspects of polymerization conditions (e.g., temperature, pressure, porosity) can affect the porosity of a polymer matrix. The porosity of a matrix can affect or determine, for example, what size molecules, complexes, or ions can enter the internal structure of a matrix; at what rate molecules, complexes, or ions may diffuse into or through such a matrix, the kinetics of any exchange processes that may occur in or on the matrix. Alternatively, there may be a relationship between the equilibrium properties of swelling (i.e., the increase in the volume of the resin based on the solvent in contact and / or the initial aqueous formulation) and ion selectivity (i.e., not all ions behave the same way toward a resin, and the swelling characteristics may further alter the ion affinity). For example, conventional gel-type ion exchange resins can be prepared by copolymerization of styrene and divinylbenzene (DVB). Gel resins usually exhibit microporosity with a pore volume of 1 nm. and 1.5nm Macroporous ion exchange resins have relatively large pores, with a pore size of 10 nm. To more than 100nm Macroporous polymers are typically highly cross-linked and therefore exhibit little volume change (swelling) when in contact with solvents, including water or aqueous formulations.

[0031] Post-recovery: As used herein, the term "post-recovery" refers to contacting the resin with a suitable solvent system, such as water (e.g., deionized water), an alcohol (e.g., methanol and / or ethanol), an organic solvent (e.g., acetone and / or tetrahydrofuran), or a mixture of two or more such solvents, to recover the chemical entity of interest, such as the purified chemical entity of interest described herein (e.g., in some embodiments, 1,6-hexanediol (HDO)), from the ion exchange resin.

[0032] Preconditioning: As used herein, the term "preconditioning" refers to a step performed on an ion exchange resin prior to contacting a sample of interest with the resin. In some embodiments, preconditioning involves contacting the ion exchange resin with a solution comprising an alternative species of ions, and / or regenerating the ion exchange resin to a preferred species of ions.

[0033] Pre-masking: As used herein, the term "pre-masking" refers to contacting an ion exchange resin with a purification target (e.g., an entity of interest, such as HDO), which in various embodiments is provided in the form of a solution. In some embodiments, the ion exchange resin is pre-masked before contacting the resin with a composition comprising the purification target, which typically contains various impurities (e.g., a fermentation broth containing the purification target). Typically, the composition of the purification target, such as a solution of the purification target, is pure or has a higher purity than the composition from which the purification target is to be purified (e.g., a fermentation broth). In some embodiments, the composition of the purification target used for pre-masking is a solution of the purification target in water or in a suitable buffer. In some embodiments, such a buffer does not contain impurities that are typically removed during purification using an ion exchange resin.

[0034] Purify: As used herein, the term "purify" and its grammatical related words (e.g., "purification", etc.) refer to the process of enriching a particular entity of interest in a composition. In some embodiments, purification may involve removing one or more components from a composition (e.g., a mixture) comprising the entity of interest. As an alternative or supplement, in some embodiments, purification may involve increasing the relative content of the entity of interest, for example, relative to one or more other components of the composition comprising the entity. In some embodiments, purification may involve one or more physical or chemical operations. For example, in some embodiments, purification may involve one or more operations in evaporation, distillation, filtration, centrifugation, liquid-liquid separation, solid-liquid separation, electrostatic fractionation, or fixed-mobile phase chromatography.

[0035] Reference: As used herein, "reference" describes a standard or control for comparison. In some embodiments, a reference or control is tested and / or determined substantially simultaneously with the testing or determination of the subject of interest. In some embodiments, a reference or control is a historical reference or control, optionally embodied in a tangible medium. Generally, as will be understood by those skilled in the art, a reference or control is determined or characterized under conditions or circumstances comparable to the conditions or circumstances being evaluated. Those skilled in the art will understand that when sufficient similarity exists, it is reasonable to rely on and compare with a particular possible reference or control.

[0036] Retentate: The retentate is the portion of a solution or mixture that is retained by a filter or porous membrane, for example, in various embodiments of the present disclosure, the term refers to the solution or slurry retained during all tangential flow filtration (TFF) unit operations.

[0037] Sample: As used herein, the term "sample" generally refers to a portion of material obtained or derived from a source of interest as described herein. In some embodiments, the source of interest is a chemical, biological, or environmental source. In some embodiments, the source of interest can be or include a cell or organism, such as a microorganism, a plant, or an animal (e.g., a human). In some embodiments, a sample is a "raw sample" obtained directly from a source of interest by any suitable means. In some embodiments, as will be apparent from the context, the term "sample" refers to a preparation obtained by treating the raw sample (e.g., by removing one or more components thereof and / or by adding one or more reagents thereto), such as by filtration (e.g., using a semipermeable membrane), and / or by adsorption onto an ion exchange resin (e.g., in ion exchange chromatography).

[0038] Small molecule: As used herein, the term "small molecule" refers to an organic and / or inorganic compound of low molecular weight. In general, "small molecule" refers to a molecule of size less than about 5 kilodaltons (kD). In some embodiments, a small molecule is less than about 4 kilodaltons, 3 kilodaltons, about 2 kilodaltons, or about 1 kilodalton. In some embodiments, a small molecule is less than about 800 daltons (D), about 600 daltons, about 500 daltons, about 400 daltons, about 300 daltons, about 200 daltons, or about 100 daltons. In some embodiments, a small molecule is less than about 2000 g / mol, less than about 1500 g / mol, less than about 1000 g / mol, less than about 800 g / mol, or less than about 500 g / mol. In some embodiments, a small molecule is not a polymer. In some embodiments, a small molecule does not include a polymer portion. In some embodiments, a specific small molecule compound may be provided and / or used in the form of a salt (e.g., in the form of an acid addition salt or a base addition salt, depending on the compound); in some such embodiments, the salt form may be a pharmaceutically acceptable salt form. In some embodiments, when the small molecule compound is a compound that exists or is found in nature, according to the present disclosure, the compound may be provided and / or used in a form different from the form that exists or is found in nature. One of ordinary skill in the art will understand that, in some embodiments, the absolute amount or relative amount of the compound in a preparation containing a specific small molecule compound, or the absolute amount or relative amount of a specific form thereof (relative to another component of the preparation, including, for example, another form of the compound), is different from the absolute amount or relative amount of the compound or form present in a reference preparation of interest (e.g., an original sample from a source of interest, such as a biological or environmental source), and the preparation is different from the form in which the compound exists in the reference preparation or source.

[0039] Strong cation exchange resin: As used herein, the term "strong cation exchange resin" refers to an ion exchange resin characterized by one or more strong acid moieties (e.g., sulfonate and / or sulfonic acid moieties) covalently attached to a polymeric support structure. In many embodiments, the strong cation exchange resin can be functionalized with one or more sulfonate and / or sulfonic acid moieties.

[0040] Strong anion exchange resin: As used herein, the term "strong anion exchange resin" refers to an ion exchange resin characterized by one or more tetrasubstituted ammonium cation moieties covalently attached to a polymer support structure. In many embodiments, the strong anion exchange resin can be functionalized with one or more tetrasubstituted ammonium moieties.

[0041] Type 1 Resin: As used herein, "Type 1 Resin" refers to a strong anion exchange resin characterized by one or more trimethylammonium cation moieties covalently attached to a polymer matrix.

[0042] Type 2 resin: As used herein, "Type 2 resin" refers to a strong anion exchange resin characterized by one or more N-hydroxyethyldimethylammonium cationic moieties covalently attached to a polymer matrix.

[0043] Weak anion exchange resin: As used herein, the term "weak anion exchange resin" refers to an ion exchange resin characterized by one or more amine and / or substituted amine (but not tetrasubstituted ammonium) moieties covalently attached to a polymer matrix. In some embodiments, the associated amines include neutral mono-, di-, or tri-substituted amines.

[0044] Weak cation exchange resin: As used herein, the term "weak cation exchange resin" refers to an ion exchange resin characterized by one or more weak acid moieties (e.g., carboxylates and / or carboxylic acid moieties) covalently attached to a polymer support structure. In many embodiments, the weak cation exchange resin is functionalized with one or more carboxylates and / or carboxylic acid moieties. DETAILED DESCRIPTION

[0045] Diol Compounds

[0046] The present disclosure provides technology related to diol compounds, for example, long-chain diol compounds, such as diol compounds containing from about 5 to about 12 carbon atoms.

[0047] Glycol compounds are useful chemicals with a wide range of applications in industrial and consumer products. For example, diol compounds have proven to be particularly useful in the production of polyurethanes, coatings, acrylates, adhesives, polyesters, resins, plasticizers, biodegradable plastics, pharmaceuticals, inks, and solvents, among other things.

[0048] It is reported that the diol compound is produced by the reduction reaction of a dicarboxylic acid (e.g., adipic acid). Large-scale (e.g., greater than about 100 grams) production of diols is generally carried out by oxidation of petroleum fractions. For example, a petroleum fraction containing benzene can be hydrogenated to produce cyclohexane. Cyclohexane can then be oxidized to produce a mixture of cyclohexanone and cyclohexanol (i.e., KA oil). Next, the KA oil is subjected to ring-opening oxidation to provide adipic acid. Adipic acid can then be completely reduced to provide 1,6-hexanediol (i.e., 1,6-hexanediol). DOI (Digital Object Identifier): 10.3389 / fchem.2020.00185. It is reported that efforts to manufacture long-chain diol compounds (e.g., 1,6-hexanediol) face challenges, at least in part due to the relative reduction state of such long-chain diol compounds and the numerous chemical transformation steps after the initial separation of benzene from crude oil. DOI: 10.15227 / orgsyn.019.0048. When preparing diol compounds of fossil origin, ion exchange is generally not performed. Ion exchange can be an important process when producing diols by biological processes such as fermentation, for example, in some embodiments, the culture contains inorganic ions and organic acids produced as metabolites.

[0049] The present disclosure provides an improved technology for producing certain diol compounds (e.g., long-chain diol compounds, such as diol compounds having 5-12 carbon atoms). In particular, the present disclosure provides a technology that enables the production of high-purity aqueous preparations of such diol compounds.

[0050] In some embodiments, the diol compound has about 5 to about 12 carbon atoms, for example, 5 to 12 carbon atoms. In some embodiments, the diol compound has about 5 to about 10 carbon atoms, for example, 5 to 10 carbon atoms. In some embodiments, the diol compound has about 5 to about 8 carbon atoms, for example, 5 to 8 carbon atoms. In some embodiments, the diol compound has about 6 carbon atoms, for example, 6 carbon atoms.

[0051] In some embodiments, the -OH group of the diol compound is located at the end of the alkyl chain.

[0052] In some embodiments, the long-chain diol compound to which the technology provided by the present disclosure can be applied can be or include one or more of 1,5-pentanediol (1,5-pentanediol (PDO)), 1,6-hexanediol (1,6-hexanediol (HDO)), 1,7-heptanediol (1,7-heptanediol (HPDO)), 1,8-octanediol (1,8-octanediol (ODO)), 1,9-nonanediol (1,9-nonanediol (NDO)), 1,10-decanediol (1,10-decanediol (DDO)), 1,11-undecanediol (1,11-undecanediol) and 1,12-dodecanediol (1,12-dodecanediol), and / or their regioisomers.

[0053] In some embodiments, the diol compound has a structure of HO-L-OH, wherein L is a divalent C 2-15 (For example, C 2-12 ,C 2-10 ,C 5-15 ,C 5-10 ,C 5-8 ,C 6-10 ,C2,C3,C4,C5,C6,C7,C8,C9,C 10 ,C 11 ,C 12 ,C 13 ,C 14 or C 15 ) aliphatic group. In some embodiments, L is linear. In some embodiments, L is branched. In some embodiments, L is saturated. In some embodiments, L is partially unsaturated. In some embodiments, L is a divalent C 2-15 (For example, C 2-12 ,C 2-10 ,C 5-15 ,C 5-10 ,C 5-8 ,C 6-10 ,C2,C3,C4,C5,C6,C7,C8,C9,C 10 ,C 11 ,C 12 ,C 13 ,C 14 or C 15 ) alkylene. In some embodiments, L is a divalent linear C 5-10In some embodiments, L is -(CH2)n-, wherein n is 2-15, 2-12, 5-15, 5-12, 6-15, 6-12, 6-10, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In some embodiments, n is 5. In some embodiments, n is 6. In some embodiments, n is 7. In some embodiments, n is 8. In some embodiments, n is 9. In some embodiments, n is 10.

[0054] In some embodiments, the diol compound is or comprises 1,5-pentanediol, 1,6-hexanediol, 1,7-heptanediol, or 1,8-octanediol. In some embodiments, the diol compound is or comprises 1,6-hexanediol. In some embodiments, the diol compound is 1,6-hexanediol.

[0055] Fermentation

[0056] Many important compounds, including diol compounds, are traditionally produced from petroleum and / or by complex chemical synthesis processes. Fermentation production has many advantages, such as being unaffected by fluctuations in the global oil market, and having fewer chemical conversion steps. In fact, fermentation processes that can utilize renewable raw materials (such as glucose or sucrose) have been developed, and no toxic by-products are produced. See, for example, WO2015 / 042201 (Zymochem), WO2020 / 220001 (Zymochem); Jiang et al., Microbiol. Cell Factories 13: 165, 2014; Beerthuis et al., Green Chemistry 17: 1341, 2015, etc., and references cited in the above-mentioned documents.

[0057] The present disclosure identifies the source of problems associated with fermentative production (e.g., fermentative production of diol compounds as described herein), particularly when the production is carried out on a large scale (e.g., greater than about 100 kg) or in a large fermentation volume (e.g., 10-1000 kL as described herein) of the total weight of the diol compound, because such production is necessarily carried out in the context of an aqueous system (e.g., cells, cell culture, or culture medium), which may complicate the subsequent isolation of the produced compound. Indeed, fermentative production often results in an aqueous system in which the diol compound of interest is present in a complex mixture (e.g., with cells and / or cellular components - e.g., cellular metabolites, etc.).

[0058] The present disclosure recognizes that when it is necessary to purify a large volume (e.g., in the range of about 10kL to about 1000kL), such as a volume of fermentation broth, the resin retention level may bring special challenges. In some embodiments, the volume is between about 10kL and about 1000kL. In some embodiments, the volume is between about 10kL and about 800kL. In some embodiments, the volume is between about 10kL and about 600kL. In some embodiments, the volume is between about 10kL and about 400kL. In some embodiments, the volume is between about 10kL and about 200kL. In some embodiments, the volume is between about 10kL and about 100kL. In some embodiments, the volume is between about 10kL and about 80kL. In some embodiments, the volume is between about 10kL and about 70kL. In some embodiments, the volume is between about 10kL and about 60kL. In some embodiments, the volume is between about 10kL and about 50kL. In some embodiments, the volume is between about 10kL and about 40kL. In some embodiments, the volume is between about 10kL and about 30kL. In some embodiments, the volume is between about 10kL and about 20kL. In some embodiments, the volume is between about 10kL and about 15kL. In some embodiments, the volume is between about 20kL and about 800kL. In some embodiments, the volume is between about 50kL and about 800kL. In some embodiments, the volume is between about 100kL and about 800kL. In some embodiments, the volume is between about 300kL and about 800kL. In some embodiments, the volume is between about 500kL and about 800kL. In some embodiments, the volume is between about 20kL and about 100kL. In some embodiments, the volume is between about 30kL and about 80kL. In some embodiments, the volume is between about 40kL and about 70kL. In some embodiments, the volume is about 10kL, 20kL, 30kL, 40kL, 50kL, 60kL, 70kL or 80kL. In some embodiments, the volume is about 10kL. In some embodiments, the volume is about 20kL. In some embodiments, the volume is about 30kL. In some embodiments, the volume is about 40kL. In some embodiments, the volume is about 50kL. In some embodiments, the volume is about 60kL. In some embodiments, the volume is about 70kL. In some embodiments, the volume is about 80kL. In some embodiments, the volume is about 90kL. In some embodiments, the volume is about 100kL. In some embodiments, the volume is about 200kL. In some embodiments, the volume is about 300kL. In some embodiments, the volume is about 400kL. In some embodiments, the volume is about 500kL. In some embodiments, the volume is about 600kL.In some embodiments, the volume is about 700 kL. In some embodiments, the volume is about 800 kL. In some embodiments, the volume is about 900 kL. In some embodiments, the volume is about 1000 kL.

[0059] Aqueous sources and initial formulations

[0060] The present disclosure provides techniques for isolating and / or purifying diol compounds from aqueous compositions (e.g., from an aqueous source, from a composition prepared therefrom, or from an aqueous composition otherwise produced).

[0061] In some embodiments, an aqueous composition (e.g., an aqueous source, an initial aqueous preparation, or other aqueous preparation) from which a diol compound can be isolated and / or purified according to the present disclosure comprises at least 50%, at least 55%, at least 60%, at least 65%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, at least 98%, or at least 99% water (w / w) (e.g., as determined by Karl Fischer titration).

[0062] The present disclosure recognizes the particular challenges faced in purifying diol compounds from aqueous preparations (e.g., aqueous source preparations and / or aqueous "initial" preparations [i.e., relative to the purification steps described herein]), and further recognizes that certain of these challenges present particular difficulties at large scale (e.g., greater than 100 kg).

[0063] For example, the present disclosure recognizes that the diol compounds described herein (e.g., long-chain diol compounds, e.g., diol compounds having at least 5 carbon atoms, such as 5-12 carbon atoms) are generally sufficiently hydrophilic that techniques such as extraction with organic solvents are ineffective in separating them from aqueous sources or initial preparations. Therefore, many typical such extraction techniques are not economical and / or useful in this context. In addition, many organic solvents are harmful to the environment; reliance on such agents to purify the diol compounds of interest risks offsetting the benefits of switching from petroleum-based production to fermentation production.

[0064] In addition, the present disclosure recognizes that, particularly when the source or initial aqueous preparation is a complex mixture (e.g., a mixture resulting from fermentation), the presence of other substances in the preparation further complicates the purification of the diol compound of interest (e.g., 1,5-pentanediol (1,5-pentanediol (PDO)), 1,6-hexanediol (1,6-hexanediol (HDO)), 1,7-heptanediol (1,7-heptanediol (HPDO)), 1,8-octanediol (1,8-octanediol (ODO)), 1,9-nonanediol (1,9-nonanediol (NDO)), 1,10-decanediol (1,10-decanediol (DDO)), 1,11-undecanediol (1,11-undecanediol), and 1,12-dodecanediol (1,12-dodecanediol) and / or their regioisomers). For example, an extraction system that fractionates a diol compound into an aqueous phase (eg, rather than an organic phase) may also fractionate many other components of the source or initial aqueous formulation into the aqueous phase, thereby failing to achieve adequate purification of the diol compound. Furthermore, techniques such as distillation or evaporation that remove primarily or only volatile components may also fail to adequately purify the diol compounds of interest (e.g., 1,5-pentanediol (1,5-pentanediol (PDO)), 1,6-hexanediol (1,6-hexanediol (HDO)), 1,7-heptanediol (1,7-heptanediol (HPDO)), 1,8-octanediol (1,8-octanediol (ODO)), 1,9-nonanediol (1,9-nonanediol (NDO)), 1,10-decanediol (1,10-decanediol (DDO)), 1,11-undecanediol (1,11-undecanediol), and 1,12-dodecanediol (1,12-dodecanediol) and / or their regioisomers) from complex aqueous sources or initial preparations.

[0065] In some embodiments, the aqueous composition (e.g., aqueous source, initial aqueous preparation or other aqueous preparation) from which the diol compound is separated or purified according to the present disclosure is or comprises a fermentation culture or a fermentation broth. In some embodiments, the aqueous composition (e.g., aqueous source or other aqueous preparation) from which the diol compound is separated or purified according to the present disclosure comprises cells, such as microbial cells (e.g., bacterial cells). In some embodiments, the optical density of the fermentation culture or fermentation broth at 600 nm may be in the range of about 10 to 200 as measured by spectrophotometry.

[0066] In some embodiments, the aqueous composition (e.g., aqueous source, initial aqueous preparation or other aqueous preparation) from which the diol compound is separated or purified according to the present disclosure is or comprises a cell component, such as a microbial (e.g., bacterial) cell component, such as an ion, lipid, metal, nucleic acid, polysaccharide, polypeptide and / or a combination thereof. In some embodiments, the microbial cell (e.g., bacterial cell) is or comprises a recombinant cell. In some embodiments, the microbial cell (e.g., bacterial cell) is or comprises a cell engineered to produce a diol compound of interest. In some embodiments, the microbial cell (e.g., bacterial cell) is engineered to produce a long-chain diol compound (e.g., having at least 5 carbon atoms, such as 5-12 carbon atoms). In some embodiments, the microbial cell (e.g., bacterial cell) is engineered to produce a diol compound, such as 1,5-pentanediol (1,5-pentanediol (PDO)), 1,6-hexanediol (1,6-hexanediol (HDO)), 1,7-heptanediol (1,7-heptanediol (HPDO)), 1,8-octanediol (1,8-octanediol (ODO)), 1,9-nonanediol (1,9-nonanediol (NDO)), 1,10-decanediol (1,10-decanediol (DDO)), 1,11-undecanediol (1,11-undecanediol), 1,12-dodecanediol (1,12-dodecanediol), regioisomers of any of the foregoing, and / or combinations thereof.

[0067] In some embodiments, the aqueous composition (e.g., aqueous source, initial aqueous preparation, or other aqueous preparation) from which the diol compound is separated or purified according to the present disclosure contains the diol compound of interest (e.g., long-chain diol compound, e.g., diol compound containing at least 5 carbon atoms, e.g., having about 5 to about 12 carbon atoms) at a concentration in the range of about 0.2 wt% to about 20 wt%. In some embodiments, the concentration is in the range of about 0.2 wt% to about 15 wt%. In some embodiments, the concentration is in the range of about 0.2 wt% to about 10 wt%. In some embodiments, the concentration is in the range of about 0.2 wt% to about 5 wt%. In some embodiments, the concentration is in the range of about 0.2 wt% to about 1 wt%. In some embodiments, the concentration is in the range of about 0.2 wt% to about 0.5 wt%. In some embodiments, the concentration is in the range of about 2 wt% to about 20 wt%. In some embodiments, the concentration is in the range of about 5 wt% to about 20 wt%. In some embodiments, the concentration is in the range of about 10 wt% to about 20 wt%. In some embodiments, the concentration is in the range of about 15wt% to about 20wt%. In some embodiments, the concentration is in the range of about 1wt% to about 18wt%. In some embodiments, the concentration is in the range of about 3wt% to about 16wt%. In some embodiments, the concentration is in the range of about 5wt% to about 14wt%. In some embodiments, the concentration is in the range of about 7wt% to about 12wt%. In some embodiments, the concentration is in the range of about 9wt% to about 11wt%. In some embodiments, the concentration is about 7wt%, 8wt%, 9wt%, 10wt%, 11wt%, 12wt% or 13wt%. In some embodiments, the concentration is about or at least about 0.2wt%. In some embodiments, the concentration is about or at least about 0.5wt%. In some embodiments, the concentration is about or at least about 1wt%. In some embodiments, the concentration is about or at least about 2wt%. In some embodiments, the concentration is about or at least about 3wt%. In some embodiments, the concentration is about or at least about 4wt%. In some embodiments, the concentration is about or at least about 5wt%. In some embodiments, the concentration is about or at least about 6wt%. In some embodiments, the concentration is about or at least about 7wt%. In some embodiments, the concentration is about or at least about 8wt%. In some embodiments, the concentration is about or at least about 9wt%. In some embodiments, the concentration is about or at least about 10wt%. In some embodiments, the concentration is about or at least about 11wt%. In some embodiments, the concentration is about or at least about 12wt%. In some embodiments, the concentration is about or at least about 13wt%. In some embodiments, the concentration is about or at least about 14wt%.In some embodiments, the concentration is about or at least about 15wt%. In some embodiments, the concentration is about or at least about 16wt%. In some embodiments, the concentration is about or at least about 17wt%. In some embodiments, the concentration is about or at least about 18wt%. In some embodiments, the concentration is about or at least about 19wt%. In some embodiments, the concentration is about or at least about 20wt%.

[0068] In some embodiments, the aqueous formulation prior to ion exchange, such as the initial aqueous formulation, contains a high concentration of ions, such as inorganic ions (e.g., sulfate, phosphate, pyruvate, lithium, sodium, potassium, ammonium, calcium, magnesium, ferrous, ferric, aluminum, chloride), organic ions (e.g., acetate, lactate, malate, succinate, maleate), amino acids (e.g., valine and / or leucine) and / or impurities. In some embodiments, the content of one or more ions and / or impurities is each independently about or at least about 50, 60, 70, 80, 90, 100, 150, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1500, 2000, 3000, 4000, 5000, 6000, 7000, 8000, or 10000 ppm (w / w). For example, in some embodiments, K + The content of Mg is about or at least about 3000 ppm (e.g., in some embodiments, about 3100 ppm). 2+ In some embodiments, the content of pyruvate is about or at least about 90 ppm. In some embodiments, the content of pyruvate is about or at least about 3000 ppm (e.g., in some embodiments, about 3200 ppm). In some embodiments, SO4 2- The content of PO4 is about or at least about 350 ppm. In some embodiments, PO4 3- The content of PO4 is about or at least about 2000 ppm (e.g., in some embodiments, about 2400 ppm). As is known to those skilled in the art, PO4 3- Can exist in various forms, such as H2PO4, HPO4 2- and PO4 3- The phosphate or PO4 described in this disclosure 3- The content / concentration of may be the sum of the contents / concentrations of all these forms.

[0069] In some embodiments, aqueous source composition, such as initial aqueous preparation, is or comprises fermentation culture.In some embodiments, aqueous source composition is derived from another aqueous source composition (such as fermentation culture), such as by one or more concentration, separation (such as, filtration) and other steps.In some embodiments, aqueous source composition has been or will be (before or after performing one or more steps specifically provided herein, such as ion exchange and / or filtration) subjected to one or more techniques for separating or purifying components, these techniques include techniques based on, for example, physical size or solubility and / or chemical properties (such as, charge or other types of affinity).For example, filtering technology can be separated according to size and / or solubility.Other techniques (such as, column chromatography) can be used for separation according to charge or other chemical properties.

[0070] In some embodiments, solid matter and / or microorganisms are removed by filtration and / or centrifugation. According to the present disclosure, various such techniques can be used. In some embodiments, filtration is or includes membrane separation. In some embodiments, the pore size of the filtration is about 10 μm or less. In some embodiments, centrifugation is or includes continuous centrifugation. Examples of continuous centrifuges include cage centrifuges, disc centrifuges, and nozzle centrifuges. In some embodiments, a technique, such as a centrifugal technique, is used in combination with another technique, such as another centrifugal technique.

[0071] In some embodiments, a membrane is used for separation. In some embodiments, the pore size of the filtration is about 10 μm or less. In some embodiments, a membrane can be used alone, or two or more membranes of different types, pore sizes, shapes, etc. can be used. In some embodiments, a membrane with a specific pore size is first used for filtration, and then a membrane with a smaller pore size is used for filtration. In some embodiments, a membrane with a specific pore size is first used for filtration, and then two or more filtrations are performed using a membrane with a smaller pore size and / or a different membrane shape.

[0072] In some embodiments, the filter membrane may provide additional advantages when pleats of different shapes and / or topologies are used. In some embodiments, the membrane is a flat membrane. In some embodiments, the membrane is a hollow fiber membrane. In some embodiments, the membrane is spiral. In some embodiments, the membrane is tubular. In some embodiments, the membrane is pleated. In some embodiments, the membrane is or includes a ceramic membrane.

[0073] In accordance with the present disclosure, a number of filtration techniques may be used, such as dead-end filtration, tangential flow filtration, and the like.

[0074] In some embodiments, cells, microorganisms, etc. are inactivated or killed (biomass inactivation) at the end of fermentation. In some embodiments, such inactivation and / or inactivation can reduce or prevent them from remaining active for a long time after fermentation, and / or being contaminated during, for example, long-term storage, downstream operations, etc. According to the present disclosure, various techniques can be used for inactivation / inactivation. For example, in some embodiments, cells, microorganisms, etc. are subjected to high temperatures, such as short-term high temperature treatment similar to pasteurization by a heat exchanger. In some embodiments, biomass inactivation is carried out at a temperature of about 50 to about 80° C., and the duration is about 1 to about 10 minutes. In some embodiments, cell lysis is reduced or prevented by flocculation or agglomeration, which can also promote better separation during cell separation. In some embodiments, a method includes biomass inactivation as described herein. In some embodiments, a method does not use biomass inactivation as described herein.

[0075] In some embodiments, the volume of the aqueous composition (e.g., aqueous source, initial aqueous preparation, or other aqueous preparation) from which the diol compound is separated or purified according to the present disclosure is between about 1 kL (kL) and about 1000 kL. In some embodiments, the volume is between about 10 kL and about 1000 kL. In some embodiments, the volume is between about 10 kL and about 800 kL. In some embodiments, the volume is between about 10 kL and about 600 kL. In some embodiments, the volume is between about 10 kL and about 400 kL. In some embodiments, the volume is between about 10 kL and about 200 kL. In some embodiments, the volume is between about 10 kL and about 100 kL. In some embodiments, the volume is between about 10 kL and about 80 kL. In some embodiments, the volume is between about 10 kL and about 70 kL. In some embodiments, the volume is between about 10 kL and about 60 kL. In some embodiments, the volume is between about 10 kL and about 50 kL. In some embodiments, the volume is between about 10kL and about 40kL. In some embodiments, the volume is between about 10kL and about 30kL. In some embodiments, the volume is between about 10kL and about 20kL. In some embodiments, the volume is between about 10kL and about 15kL. In some embodiments, the volume is between about 20kL and about 800kL. In some embodiments, the volume is between about 50kL and about 800kL. In some embodiments, the volume is between about 100kL and about 800kL. In some embodiments, the volume is between about 300kL and about 800kL. In some embodiments, the volume is between about 500kL and about 800kL. In some embodiments, the volume is between about 20kL and about 100kL. In some embodiments, the volume is between about 30kL and about 80kL. In some embodiments, the volume is between about 40kL and about 70kL. In some embodiments, the volume is about 10kL, 20kL, 30kL, 40kL, 50kL, 60kL, 70kL or 80kL. In some embodiments, the volume is about or at least about 10kL. In some embodiments, the volume is about or at least about 20kL. In some embodiments, the volume is about or at least about 30kL. In some embodiments, the volume is about or at least about 40kL. In some embodiments, the volume is about or at least about 50kL. In some embodiments, the volume is about or at least about 60kL. In some embodiments, the volume is about or at least about 70kL. In some embodiments, the volume is about or at least about 80kL. In some embodiments, the volume is about or at least about 90kL. In some embodiments, the volume is about or at least about 100kL. In some embodiments, the volume is about or at least about 200kL. In some embodiments, the volume is about or at least about 300kL.In some embodiments, the volume is about or at least about 400 kL. In some embodiments, the volume is about or at least about 500 kL. In some embodiments, the volume is about or at least about 600 kL. In some embodiments, the volume is about or at least about 700 kL. In some embodiments, the volume is about or at least about 800 kL. In some embodiments, the volume is about or at least about 900 kL. In some embodiments, the volume is about or at least about 1000 kL.

[0076] The present disclosure provides a variety of techniques that can be used to purify diol compounds, such as from aqueous preparations that may contain other ionizable molecules and / or insoluble materials. Specific techniques provided relate to separating diol compounds described herein (e.g., 1,5-pentanediol (1,5-pentanediol (PDO)), 1,6-hexanediol (1,6-hexanediol (HDO)), 1,7-heptanediol (1,7-heptanediol (HPDO)), 1,8-octanediol (1,8-octanediol (ODO)), 1,9-nonanediol (1,9-nonanediol (NDO)), 1,10-decanediol (1,10-decanediol (DDO)), 1,11-undecanediol (1,11-undecanediol) and 1,12-dodecanediol (1,12-dodecanediol) and / or their regioisomers) from aqueous preparations (e.g., from aqueous source preparations).

[0077] In some embodiments, the initial aqueous formulation according to the present disclosure may be or include cells (e.g., microbial cells) or cultures thereof, or culture media therefrom, which include diol compounds described herein (e.g., 1,5-pentanediol (1,5-pentanediol (PDO)), 1,6-hexanediol (1,6-hexanediol (HDO)), 1,7-heptanediol (1,7-heptanediol (HPDO)), 1,8-octanediol (1,8-octanediol (ODO)), 1,9-nonanediol (1,9-nonanediol (NDO)), 1,10-decanediol (1,10-decanediol (DDO)), 1,11-undecanediol (1,11-undecanedi ...

[0078] -undecandiol) and 1,12-dodecanediol (1,12-dodecanediol) and / or its regioisomers), for example, which may have been fermented; in some embodiments, the initial aqueous formulation is a formulation prepared from a fermentation composition. In some embodiments, the initial aqueous formulation comprises one or more cells or cellular components. In some embodiments, the initial aqueous formulation does not comprise cellular material (e.g., is prepared from a non-cellular source and / or is otherwise substantially free of cellular components).

[0079] Those skilled in the art will appreciate upon reading this disclosure that many of its teachings apply to aqueous formulations (eg, initial aqueous formulations), regardless of the original source from which they may have come, or how they may otherwise have been prepared.

[0080] In some embodiments, the initial aqueous formulation comprises phosphate. In some embodiments, the initial aqueous formulation comprises sulfate. In some embodiments, the initial aqueous formulation comprises pyruvate. In some embodiments, the initial aqueous formulation comprises a diol compound. In some embodiments, the initial aqueous formulation comprises 1,6-hexanediol (1,6-hexanediol). In some embodiments, the initial aqueous formulation comprises DNA and DNA fragments. In some embodiments, the initial aqueous formulation comprises RNA and RNA fragments. In some embodiments, the initial aqueous formulation comprises glucose. In some embodiments, the initial aqueous formulation comprises palmitic acid and palmitic acid. In some embodiments, the initial aqueous formulation comprises oleate and oleic acid. In some embodiments, the initial aqueous formulation comprises glycerol.

[0081] In some embodiments, the initial aqueous preparation is substantially free of insoluble microbial cell material. In some embodiments, the initial aqueous preparation is substantially free of insoluble bacterial cell material. In some embodiments, the initial aqueous preparation is substantially free of glycerol. In some embodiments, the initial aqueous preparation is substantially free of cellulose. In some embodiments, the initial aqueous preparation is substantially free of peptidoglycan. In some embodiments, the initial aqueous preparation is substantially free of teichoic acid. In some embodiments, the initial aqueous preparation is substantially free of protein and protein fragments. In some embodiments, the initial aqueous preparation is substantially free of lipopolysaccharide. In some embodiments, the initial aqueous preparation is substantially free of molecules with a molecular weight greater than 5 kilodaltons (kD). In some embodiments, the initial aqueous preparation is substantially free of molecules with a molecular weight greater than 200 daltons (D). In some embodiments, the aqueous preparation is substantially free of cells (e.g., bacterial cells), proteins, polysaccharides, multivalent ions, and / or compounds with a molecular weight of about 200, 500, 1000, 2000 or 5000. In some embodiments, provided techniques include microfiltration, which can remove or reduce the content of, for example, bacterial cells, proteins, polysaccharides, and / or compounds with a molecular weight of 5000. In some embodiments, provided techniques include nanofiltration, which can remove or reduce the content of, for example, peptides, multivalent ions, and / or compounds with a molecular weight of 5000.

[0082] In some embodiments, the aqueous formulation (e.g., the initial aqueous formulation) comprises hydrochloric acid. In some embodiments, the aqueous formulation (e.g., the initial aqueous formulation) comprises sodium hydroxide. In some embodiments, the aqueous formulation (e.g., the initial aqueous formulation) comprises a mixture of diol compounds.

[0083] In some embodiments, an aqueous formulation (e.g., an initial aqueous formulation) to which the provided technology, particularly the provided ion exchange (IEX) process, is applied has been pH adjusted, for example, to increase or decrease the ionic strength of the aqueous formulation to preferentially target ions of interest.

[0084] In some embodiments, an aqueous preparation (e.g., an initial aqueous preparation) to which the provided technology, and in particular the provided ion exchange (IEX) processes, are applied (i) contains a plurality of different chemical entities (e.g., containing a diol compound of interest and one or more other entities from which the diol compound is to be separated) that are not readily distinguishable from one another based on size exclusion / separation (e.g., by filtration), and / or (ii) has been subjected to one or more size exclusion / separation (e.g., filtration) treatments.

[0085] Among other things, the present disclosure provides particularly useful techniques for treating certain aqueous preparations (e.g., fermentation cultures or preparations produced therefrom), particularly by filtration. For example, the present disclosure demonstrates the particular utility of certain microfiltration processes.

[0086] In some embodiments, an aqueous formulation (e.g., an initial aqueous formulation) using the provided technology, particularly the provided ion exchange (IEX) process, is characterized in that its optical density is reduced compared to the fermentation culture (e.g., from which the aqueous formulation is prepared). In some embodiments, an aqueous formulation (e.g., an initial aqueous formulation) using the provided technology, particularly the provided ion exchange (IEX) process, is characterized in that its conductivity (e.g., measured in μS / cm) is in the range of about 10-5000 (e.g., about 10, 20, 50, 100, 200, 500, 1000, 2000, 3000, 4000, 5000, etc.) μS / cm. In some embodiments, the conductivity of the initial aqueous formulation is between about 10 μS / cm and about 5000 μS / cm. In some embodiments, the conductivity of the initial aqueous formulation is between about 10 μS / cm and about 4000 μS / cm. In some embodiments, the conductivity of the initial aqueous formulation is between about 10 μS / cm and about 3000 μS / cm. In some embodiments, the conductivity of the initial aqueous formulation is between about 10 μS / cm and about 2000 μS / cm. In some embodiments, the conductivity of the initial aqueous formulation is between about 10 μS / cm and about 1000 μS / cm. In some embodiments, the conductivity of the initial aqueous formulation is between about 10 μS / cm and about 500 μS / cm. In some embodiments, the conductivity of the initial aqueous formulation is between about 10 μS / cm and about 100 μS / cm. In some embodiments, the conductivity of the initial aqueous formulation is between about 50 μS / cm and about 5000 μS / cm. In some embodiments, the conductivity of the initial aqueous formulation is between about 75 μS / cm and about 5000 μS / cm. In some embodiments, the conductivity of the initial aqueous formulation is between about 100 μS / cm and about 5000 μS / cm. In some embodiments, the conductivity of the initial aqueous formulation is between about 50 μS / cm and about 1000 μS / cm. In some embodiments, the conductivity of the initial aqueous formulation is between about 75 μS / cm and about 500 μS / cm. In some embodiments, the conductivity of the initial aqueous formulation is between about 90 μS / cm and about 110 μS / cm. In some embodiments, the conductivity of the initial aqueous formulation is about 70 μS / cm, 85 μS / cm, 100 μS / cm, 115 μS / cm, or 130 μS / cm. In some embodiments, the conductivity of the initial aqueous formulation is about 70 μS / cm. In some embodiments, the conductivity of the initial aqueous formulation is about 80 μS / cm. In some embodiments, the conductivity of the initial aqueous formulation is about 90 μS / cm. In some embodiments, the conductivity of the initial aqueous formulation is about 100 μS / cm. In some embodiments, the conductivity of the initial aqueous formulation is about 110 μS / cm.In some embodiments, the conductivity of the initial aqueous formulation is about 120 μS / cm. In some embodiments, the conductivity of the initial aqueous formulation is about 130 μS / cm. In some embodiments, the conductivity of the initial aqueous formulation is about 150 μS / cm. In some embodiments, the conductivity of the initial aqueous formulation is about 200 μS / cm.

[0087] Ion Exchange (IEX)

[0088] Among other aspects, the present disclosure provides ion exchange chromatography (IEX) techniques that can be used to separate and / or purify diol compounds (e.g., long-chain diol compounds, such as those having at least 5, e.g., 5-12 carbon atoms). It is understood by those skilled in the art that diol compounds contain an alcohol moiety, are generally soluble in water, and may be difficult to distinguish (e.g., by chromatography) from other polar molecules in an aqueous formulation, particularly when they are intimately mixed with one another. Selectively separating the alcohol functional group from an aqueous formulation, particularly when the aqueous formulation contains one or more other cations and / or anions, may present daunting technical challenges.

[0089] The present disclosure provides techniques to overcome these challenges.

[0090] Among other things, this disclosure provides the following insights:

[0091] (i) particularly good results (e.g., less resin retention) can be achieved for purifying diol compounds described herein (e.g., long-chain diol compounds, such as diol compounds having at least 5 carbon atoms, and in some embodiments, 5-12 carbon atoms), particularly when purifying such compounds from aqueous sources (e.g., fermentation cultures or compositions obtained therefrom) by using hydrophilic resins (e.g., compared to the results that can be achieved using typical hydrophobic resins such as polystyrene supports);

[0092] (ii) contacting the resin with the diol compound prior to separating the diol compound from a sample (e.g., from an aqueous sample, such as an initial aqueous formulation as described herein) using a chromatographic resin (e.g., an ion exchange resin) can increase the purification efficiency of the resin. That is, more of the diol compound will pass through the resin that has been pretreated as described herein compared to an otherwise similar resin that has not been so pretreated;

[0093] (iii) exposing the chromatographic resin that has retained a diol compound as described herein (e.g., a long chain diol compound, such as a diol compound having at least 5 carbon atoms, and in some embodiments, 5-12 carbon atoms) to an aqueous solution (e.g., a pre-ion exchange composition or an aqueous sample, such as an initial aqueous formulation as described herein) comprising the diol compound to facilitate removal of non-diol compound species from the solution more than removal of the diol compound; and

[0094] (iv) washing the chromatographic resin having retained the diol compound described herein (e.g., a long-chain diol compound, such as a diol compound having at least 5 carbon atoms, and in some embodiments, 5-12 carbon atoms) with a suitable solvent system, such as water, alcohols (e.g., short-chain alcohols, such as methanol and ethanol), organic solvents (e.g., tetrahydrofuran (THF) and acetone), and mixtures of two or more of these solvents, to effectively recover the diol compound.

[0095] Resin

[0096] In some embodiments, the present disclosure provides a surprising teaching that hydrophilic ion exchange resins can be particularly effective in purifying diol compounds (e.g., long chain diol compounds, such as diol compounds having at least 5 carbon atoms, and in some embodiments, 5-12 carbon atoms) from aqueous preparations.

[0097] In some embodiments, ion exchange (IEX) resins used in accordance with the present disclosure are hydrophilic.

[0098] In some embodiments, the ion exchange (IEX) resins used in accordance with the present disclosure are lipophobic.

[0099] In some embodiments, the ion exchange (IEX) resins used in accordance with the present disclosure are lipophilic.

[0100] In some embodiments, ion exchange (IEX) resins used in accordance with the present disclosure are hydrophobic.

[0101] In some embodiments, the ion exchange (IEX) resin used according to the present disclosure is or comprises a polymer (e.g., a functionalized polymer). In some embodiments, the ion exchange (IEX) resin is or comprises polystyrene, polyacrylate or polymethacrylate. In some embodiments, the ion exchange (IEX) resin comprises a base polymer functionalized with an acidic or basic group. In some embodiments, the ion exchange (IEX) base polymer is polystyrene, polyacrylate or polymethacrylate. In some embodiments, the ion exchange (IEX) base polymer comprises crosslinking and / or copolymerization, for example with a difunctional monomer, such as divinylbenzene (DVB). In some embodiments, the base polymer is functionalized by introducing an acidic group (e.g., a sulfonate group). In some embodiments, the base polymer is functionalized by introducing an amine group. In some embodiments, the base polymer is functionalized by introducing a quaternary ammonium group. In some embodiments, the ion exchange (IEX) resin is or comprises a cation exchange resin. In some embodiments, the cation exchange resin is or comprises a styrene-divinylbenzene (DVB) resin with an acidic group. In some embodiments, the cation exchange resin is or comprises a styrene-divinylbenzene (DVB) resin with a sulfonate group. In some embodiments, the ion exchange (IEX) resin is or comprises an anion exchange resin. In some embodiments, the anion exchange resin is or comprises an acrylic acid-divinylbenzene (DVB) resin. In some embodiments, the anion exchange resin is or comprises an acrylic acid-divinylbenzene (DVB) resin with a quaternary ammonium group.

[0102] In some embodiments, the ion exchange (IEX) resin is or comprises a polystyrene support structure.

[0103] In some embodiments, the ion exchange resin is or comprises a polyacrylate support structure.

[0104] In some embodiments, the ion exchange resin is or comprises a polymethacrylate support structure.

[0105] In some embodiments, the ion exchange resin is a cross-linked resin. In some embodiments, the degree of cross-linking is in the range of about 1% to about 40%. In some embodiments, the degree of cross-linking is in the range of about 1% to about 35%. In some embodiments, the degree of cross-linking is in the range of about 1% to about 30%. In some embodiments, the degree of cross-linking is in the range of about 1% to about 25%. In some embodiments, the degree of cross-linking is in the range of about 1% to about 20%. In some embodiments, the degree of cross-linking is in the range of about 2% to about 20%. In some embodiments, the degree of cross-linking is in the range of about 3% to about 20%. In some embodiments, the degree of cross-linking is in the range of about 4% to about 20%. In some embodiments, the degree of cross-linking is in the range of about 4% to about 15%. In some embodiments, the degree of cross-linking is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19% or 20%. In some embodiments, the degree of crosslinking is about 1%. In some embodiments, the degree of crosslinking is about 2%. In some embodiments, the degree of crosslinking is about 4%. In some embodiments, the degree of crosslinking is about 5%. In some embodiments, the degree of crosslinking is about 10%. In some embodiments, the degree of crosslinking is about 15%. In some embodiments, the degree of crosslinking is about 20%.

[0106] In some embodiments, the ion exchange resin is or comprises a polystyrene resin. In some embodiments, the ion exchange resin is or comprises a polyacrylic resin. In some embodiments, the ion exchange resin is or comprises a hydrogel system. In some embodiments, the ion exchange resin is or comprises a gel type, a porous type and / or a highly porous type.

[0107] In some embodiments, the ion exchange resin is or comprises a gel. In some embodiments, the ion exchange resin is or comprises a powder. In some embodiments, the ion exchange resin is or comprises a sphere. In some embodiments, the ion exchange resin is or comprises a fiber. In some embodiments, the ion exchange resin is or comprises a membrane. In some embodiments, the ion exchange resin is or comprises a microporous material. In some embodiments, the ion exchange resin is or comprises a macroporous material. In some embodiments, crosslinking (e.g., degree of crosslinking and / or type of crosslinking) determines one or more material properties of the carrier matrix (e.g., gel properties, porosity, pore size, etc.).

[0108] In some embodiments, the resin is functionalized by various groups as described herein. In some embodiments, the average functional group density of the resin is about 0.1 to 4.0 (e.g., about 0.1-3.5, 0.1-3.0, 0.1-2.0 or 0.5-3.0) eq / L. In some embodiments, it is about 0.1 eq / L. In some embodiments, it is about 0.2 eq / L. In some embodiments, it is about 0.3 eq / L. In some embodiments, it is about 0.5 eq / L. In some embodiments, it is about 1.0 eq / L. In some embodiments, it is about 1.5 eq / L. In some embodiments, it is about 2.0 eq / L. In some embodiments, it is about 2.5 eq / L. In some embodiments, it is about 3.0 eq / L. In some embodiments, it is about 3.5 eq / L. In some embodiments, it is about 4.0 eq / L.

[0109] Particle size

[0110] In some embodiments, the ion exchange resin used in accordance with the present disclosure is characterized by its particle size.

[0111] In some embodiments, the average particle size is between about 100 μm and about 1500 μm. In some embodiments, the average particle size is between about 100 μm and about 1100 μm. In some embodiments, the average particle size is between about 100 μm and about 800 μm. In some embodiments, the average particle size is between about 100 μm and about 500 μm. In some embodiments, the average particle size is between about 500 μm and about 1500 μm. In some embodiments, the average particle size is between about 1000 μm and about 1500 μm. In some embodiments, the average particle size is between about 200 μm and about 1300 μm. In some embodiments, the average particle size is between about 300 μm and about 1100 μm. In some embodiments, the average particle size is between about 400 μm and about 1000 μm. In some embodiments, the average particle size is between about 500 μm and about 900 μm. In some embodiments, the average particle size is between about 600 μm and about 800 μm. In some embodiments, the average particle size is between about 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, or 1500 μm.

[0112] Porosity

[0113] In some embodiments, ion exchange resins used in accordance with the present disclosure are characterized by their porosity.

[0114] According to the present disclosure, resins with various porosity sizes can be used. In some embodiments, the porosity is between about 1nm and about 250nm. In some embodiments, the porosity is between about 1nm and about 175nm. In some embodiments, the porosity is between about 1nm and about 150nm. In some embodiments, the porosity is between about 1nm and about 125nm. In some embodiments, the porosity is between about 1nm and about 100nm. In some embodiments, the porosity is between about 1nm and about 75nm. In some embodiments, the porosity is between about 1nm and about 60nm. In some embodiments, the porosity is between about 1nm and about 50nm.

[0115] Functional Group

[0116] In some embodiments, the ion exchange resin comprises functional groups.In some embodiments, the ion exchange resin used comprises functional groups that are compatible with / particularly suitable for use in purifying a particular diol compound of interest.

[0117] In some embodiments, the ion exchange resin is or comprises a cation exchange resin. In some embodiments, the ion exchange resin is or comprises a strong cation exchange resin. In some embodiments, the strong cation exchange resin is or comprises a strong acid portion covalently attached to a polymer support structure. In some embodiments, the strong cation exchange resin is or comprises one or more sulfonate and / or sulfonic acid portions covalently attached to a polymer support structure. In some embodiments, the strong cation exchange resin is commercially available, for example, SK1BH, DIAION, a product of Mitsubishi Corporation of Tokyo, Japan.

[0118] In some embodiments, the ion exchange resin is or comprises a weak cation exchange resin. In some embodiments, the weak cation exchange resin is or comprises one or more carboxylates and / or carboxylic acid moieties covalently attached to a polymer support structure. In some embodiments, strong cation exchange resins are commercially available, for example, WK60L, WK10, etc.

[0119] In some embodiments, the ion exchange resin is or comprises an anion exchange resin. In some embodiments, the ion exchange resin is or comprises a weak anion exchange resin. In some embodiments, the weak anion exchange resin is or comprises one or more amines and / or substituted amine moieties (but not tetrasubstituted ammonium moieties) covalently linked to the polymer support structure; in some such embodiments, the amine comprises a neutral monosubstituted, disubstituted or trisubstituted amine. In some embodiments, the weak anion exchange resin is commercially available, for example, WA21J, IRA67, etc.

[0120] In some embodiments, the ion exchange resin is or comprises a strong anion exchange resin. In some embodiments, the strong anion exchange resin is or comprises one or more tetrasubstituted ammonium cation moieties covalently attached to the polymer support structure. In many embodiments, the strong anion exchange resin is functionalized with one or more tetrasubstituted ammonium moieties. In some embodiments, the strong anion exchange resin is commercially available, for example, SA10AOH, HPR4580Cl, SCAV4Cl, etc.

[0121] Anion Exchange Resin - Type 1

[0122] In some embodiments, the strong anion exchange resin is or comprises one or more trimethylammonium cation moieties covalently attached to a polymeric support structure.

[0123] HPR4580Cl (strong anion exchange resin): A commercial example of a type 1 strong anion exchange resin comprising a gel-like polyacrylate. DuPont, Wilmington, Delaware, USA. Physicochemical properties: (a) polyacrylic acid gel; (b) strong anion exchange resin; (c) type 1; (d) molar equivalent: ≥1.25 eq / L (Cl - form); (e) water retention capacity: 58.0%–62.0% (Cl - form); (f) particle size: 700 μm–950 μm; (g) swelling (Cl - -->OH - )≤25%.

[0124] SCAV4Cl (Strong Anion Exchange Resin): A commercial example of a Type 1 strong anion exchange resin comprising a macroporous polyacrylate. DuPont, Wilmington, Delaware, USA. Physicochemical properties: (a) Macroporous polyacrylic acid; (b) Strong anion exchange resin; (c) Type 1; (d) Molar equivalent: ≥0.80 eq / L (Cl - form); (e) water retention capacity: 66.0%–72.0% (Cl - form); (f) particle size: 630 μm–850 μm.

[0125] Anion Exchange Resin - Type 2

[0126] In some embodiments, the strong anion exchange resin is or comprises one or more dimethylethanolammonium cationic moieties covalently attached to a polymeric support structure.

[0127] Preprocessing

[0128] In some embodiments, before an initial aqueous formulation described herein (e.g., containing a diol compound of interest, which can be a diol compound used in a pretreatment) is contacted with an ion exchange (IEX) resin, the IEX resin can be subjected to one or more pretreatment steps.

[0129] In some embodiments, pretreatment includes exposing the IEX resin to one or more of the following, depending on the resin type: water (e.g., deionized water; e.g., for H-type resin), hydroxide (e.g., aqueous hydroxide solution; e.g., LiOH (e.g., aqueous LiOH), NaOH (e.g., aqueous NaOH), KOH (e.g., aqueous KOH)), strong acid (e.g., aqueous acid), etc.

[0130] Alternatively or additionally, in some embodiments, the pretreatment includes one or more pre-masking steps, wherein the IEX resin is pretreated with a diol compound before the initial aqueous formulation described herein (e.g., containing a diol compound of interest, which may be a diol compound used in the pretreatment) is contacted with the IEX resin. For pre-masking, the diol compound may be provided in the form of a solution. Typically, such a solution contains very little or low levels of impurities, such as ions, compared to the composition from which the diol compound is purified (e.g., the initial formulation). For example, in some embodiments, the concentration of each ion or impurity is independently about or no more than about 50, 40, 30, 20, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, 0.5, 0.2, or 0.1 ppm (w / w). In some embodiments, the diol compound is provided in the form of an aqueous solution. In some embodiments, the diol compound is provided in the form of a solution of a pure compound, such as an aqueous solution. In some embodiments, the concentration of the solution (e.g., a pre-masking solution) is no more than about 50%, for example, the concentration of the diol compound is about 0.1%-50%, or about 0.1%, 0.2%, 0.5%, 1%, 2%, 5%, 10%, 15%, 20%, 25%, 30%, 40% or 50% (wt %).

[0131] In some embodiments, the amount of diol compound applied is about or at least about 1-1000 mg / mL resin, for example, about 1-500, 1-200, 1-100, 1-50, 1-20, 1-10, or about 1, 2, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 150, 200, 300, 400, 500, 600, 700, 800, 900 or 1000 mg / mL resin. In some embodiments, it is about 1 mg / mL resin. In some embodiments, it is about 2 mg / mL resin. In some embodiments, it is about 5 mg / mL resin. In some embodiments, it is about 10 mg / mL resin. In some embodiments, it is about 20 mg / mL resin. In some embodiments, it is about 50 mg / mL resin. In some embodiments, it is about 100 mg / mL resin. In some embodiments, it is about 150 mg / mL resin. In some embodiments, it is about 200 mg / mL resin. In some embodiments, it is about 500 mg / mL resin. In some embodiments, it is about 1000 mg / mL resin.

[0132] In some embodiments, the initial aqueous formulation has been pH adjusted or otherwise treated to enhance retention of the diol compound of interest on the IEX resin relative to at least one other component of the initial aqueous composition.

[0133] In some embodiments, the initial aqueous composition may have been treated to protonate the functional groups (e.g., by a strong proton donor, such as a strong acid), e.g., to form cations. Without wishing to be bound by any particular theory, it is speculated that such positively charged cations in the initial aqueous formulation may exhibit preferential electrostatic interactions near the surface of the ion exchange resin.

[0134] Alternatively or additionally, in some embodiments, the initial aqueous formulation may have been pH adjusted (or otherwise treated) to deprotonate the functional groups, e.g., to form anions. Without wishing to be bound by any particular theory, it is speculated that such negatively charged anions in the initial aqueous formulation may exhibit electrostatic interactions near the surface of the ion exchange resin.

[0135] In some embodiments of the present disclosure, the IEX resin is pretreated (e.g., pre-masked) with a protonated or deprotonated form of the compound of interest; in some such embodiments, the IEX resin is then contacted with an initial aqueous formulation comprising the protonated or deprotonated form.

[0136] In some embodiments, the pre-masking step comprises contacting the IEX resin with an aqueous solution comprising about 0.1% to about 50% by weight of the diol compound; in some embodiments, the range is between about 0.1% and about 2%. In some embodiments, the IEX resin is contacted with an aqueous solution comprising about 0.5% by weight of the diol compound of interest. In some embodiments, the IEX resin is contacted with an aqueous solution comprising about 0.1% by weight of the diol compound of interest.

[0137] In some embodiments, pre-masking involves contacting for a period of time of about 20 minutes, about 30 minutes, about 40 minutes, about 50 minutes, about 60 minutes, about 70 minutes, about 80 minutes, about 90 minutes or more, optionally under mixing (e.g., stirring) conditions. In some embodiments, the period of time is about 60 minutes.

[0138] In some embodiments, pre-masking significantly reduces the loss of diol compounds. In some embodiments, it reduces the loss by about or at least about 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10 times (loss without post-recovery / loss with post-recovery). In some embodiments, the reduction is about or at least about 1.5 times.

[0139] In some embodiments, it is about or at least about 2 times. In some embodiments, it is about or at least about 5 times. In some embodiments, it is about or at least about 10 times.

[0140] In some embodiments, pretreatment is carried out in batch, column or continuous flow method. In some embodiments, pretreatment is carried out in batch method. In some embodiments, pretreatment is carried out in column method. In some embodiments, pretreatment is carried out in continuous flow method.

[0141] Purification

[0142] According to the present disclosure, a preparation, such as an initial aqueous preparation, is purified by contacting with an IEX resin as described herein (e.g., by IEX chromatography) (e.g., contacting with a resin that has been pretreated - e.g., a resin that has been pre-masked as described herein) and / or contacting with a resin that has been washed as described herein. Alternatively or additionally, in some embodiments, the initial aqueous preparation is purified by contacting with a hydrophilic IEX resin. In some embodiments, the initial aqueous preparation is purified by contacting with a hydrophobic IEX resin. In some embodiments, the hydrophilic resin has a lower loss of the purification target (e.g., a diol compound (e.g., a diol compound containing about 5 to about 12 carbon atoms, such as 1,6-hexanediol (HDO))) than the hydrophobic resin. In some embodiments, pre-masking reduces the loss of the purification target (e.g., a diol compound (e.g., a diol compound containing about 5 to about 12 carbon atoms, such as 1,6-hexanediol (HDO))).

[0143] In some embodiments, a preparation, such as an initial aqueous preparation, is purified by contacting with a cation exchange resin. In some embodiments, it is contacted with an anion exchange resin. In some embodiments, it is contacted with both a cation exchange resin and an anion exchange resin. In some embodiments, it is first contacted with a cation exchange resin and then with an anion exchange resin. In some embodiments, exchanging cations before exchanging anions can bring various benefits, such as reducing or preventing the formation of insoluble inorganic metal hydroxide complexes. In some embodiments, it is first contacted with an anion exchange resin and then with a cation exchange resin. In some embodiments, the cation exchange resin is a strong cation exchange resin. In some embodiments, the anion exchange resin is a strong anion exchange resin. In some embodiments, the composition is contacted with a cation exchange resin and an anion exchange resin simultaneously.

[0144] In some embodiments, contact with the resin, such as ion exchange, is performed in a batch, column, or continuous flow process. In some embodiments, it is performed in a batch process. In some embodiments, it is performed in a column process. In some embodiments, it is performed in a continuous flow process.

[0145] Purification, such as ion exchange, can be performed at various suitable temperatures. Useful ion exchange conditions exist and can be utilized in accordance with the present disclosure. For example, in some embodiments, ion exchange is performed at about ambient temperature. In some embodiments, ion exchange is performed at a temperature above ambient temperature, for example, about 40°C.

[0146] Compositions, such as preparations, are usually in contact with resins for a sufficiently long time. In some embodiments, whether the time is sufficient is assessed by the desired degree of ion exchange. In some embodiments, whether the time is sufficient is assessed by the degree of impurity removal. In some embodiments, whether the time is sufficient is assessed by the percentage of product loss and / or recovery. In some embodiments, the time is about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 hours or longer. In some embodiments, the time is about 1 hour. In some embodiments, the time is about 2 hours. In some embodiments, the time is about 3 hours. In some embodiments, the time is about 4 hours. In some embodiments, the time is about 5 hours.

[0147] Post-processing

[0148] In some embodiments, the provided techniques include post-treating one or more compositions or resins after contacting the formulation with the resin. In some embodiments, the post-treatment is or includes post-recovery. In various embodiments, for example, used alone or in combination with one or more other techniques provided herein, an IEX resin to which a diol compound of interest has been adsorbed (e.g., adsorbed from an initial aqueous formulation and / or pre-masking) is washed (e.g., with water [e.g., deionized water] or an alcohol, such as a short-chain alcohol, such as ethanol or methanol), or a mixture thereof, to release the adsorbed diol compound from the resin.

[0149] According to the present disclosure, various solvent systems can be used to wash the resin. For example, in some embodiments, the solvent system is or comprises water. In some embodiments, the solvent system is or comprises alcohol. In some embodiments, the solvent system is or comprises short-chain alcohols, such as methanol or ethanol. In some embodiments, the solvent system is or comprises a water-soluble organic solvent, such as tetrahydrofuran and / or acetone. In some embodiments, the solvent system is or comprises water, methanol, ethanol, isopropanol, tetrahydrofuran, acetone, or a mixture of two or more thereof. In some embodiments, the solvent system is or comprises water. In some embodiments, the solvent system is or comprises methanol. In some embodiments, the solvent system is or comprises ethanol. In some embodiments, the solvent system is or comprises isopropanol. In some embodiments, the solvent system is or comprises tetrahydrofuran. In some embodiments, the solvent system is or comprises acetone. In some embodiments, the boiling point of the organic solvent under normal pressure or reduced pressure (for example, pressure for evaporation and / or distillation) is lower than water. Those skilled in the art can easily evaluate the effectiveness of a solvent system (whether a single solvent or a mixture of two or more solvents) for washing away diol compounds from resin according to the present disclosure. The rear recovery solvent system is generally a pure solvent system, free of ions and other compounds except the solvent therein. In some embodiments, the total ion content of the rear recovery solvent system is no more than about 1000, 900, 800, 700, 600, 500, 400, 300, 200, 100, 90, 80, 70, 60, 50, 40, 30, 20, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1ppm (wt / wt). In some embodiments, it is no more than about 100ppm. In some embodiments, it is no more than about 50ppm. In some embodiments, it is no more than about 10ppm. In some embodiments, it is no more than about 5ppm. In some embodiments, it is no more than about 1ppm. In some embodiments, it is no more than about 0.5ppm. In some embodiments, it is no more than about 0.1ppm. In some embodiments, the total impurity content of the post-recovery solvent system does not exceed about 1000, 900, 800, 700, 600, 500, 400, 300, 200, 100, 90, 80, 70, 60, 50, 40, 30, 20, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 ppm (wt / wt). In some embodiments, it does not exceed about 100 ppm. In some embodiments, it does not exceed about 50 ppm. In some embodiments, it does not exceed about 10 ppm. In some embodiments, it does not exceed about 5 ppm. In some embodiments, it does not exceed about 1 ppm. In some embodiments, it does not exceed about 0.5 ppm. In some embodiments, it does not exceed about 0.1 ppm.

[0150] In some embodiments, at the time of post-recovery, about or at least about 1 to 100 mL of solvent system is used per 1 mL of resin (mL / mL), for example, about 1-50, 1-20, 1-10, 2-10, 5-10, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90 or 100 mL of solvent system. In some embodiments, it is about 1 mL / mL. In some embodiments, it is about 2 mL / mL. In some embodiments, it is about 3 mL / mL. In some embodiments, it is about 4 mL / mL. In some embodiments, it is about 5 mL / mL. In some embodiments, it is about 6 mL / mL. In some embodiments, it is about 7 mL / mL. In some embodiments, it is about 8 mL / mL. In some embodiments, it is about 9 mL / mL. In some embodiments, it is about 10 mL / mL. In some embodiments, it is about 15 mL / mL. In some embodiments, it is about 20 mL / mL. In some embodiments, it is about 30 mL / mL. In some embodiments, it is about 40 mL / mL. In some embodiments, it is about 50 mL / mL.

[0151] In some embodiments, the post-treatment washing is performed for a period of at least about 20 minutes, about 30 minutes, about 40 minutes, about 50 minutes, about 60 minutes, about 70 minutes, about 80 minutes, about 90 minutes or more. In some embodiments, the period is about 60 minutes.

[0152] In some embodiments, the post-recovery significantly reduces the loss of diol compounds. In some embodiments, it reduces the loss by about or at least about 1.5, 2, 3, 4, 5, 6, 7, 8, 9 or 10 times (loss without post-recovery / loss with post-recovery). In some embodiments, the reduction is about or at least about 1.5 times. In some embodiments, it is about or at least about 2 times. In some embodiments, it is about or at least about 5 times. In some embodiments, it is about or at least about 10 times.

[0153] In some embodiments, pre-masking and post-recovery are used simultaneously, and they significantly reduce the loss of diol compounds. In some embodiments, they reduce the loss by about or at least about 1.5, 2, 3, 4, 5, 6, 7, 8, 9 or 10 times (loss of post-recovery without / loss of post-recovery). In some embodiments, the reduction is about or at least about 1.5 times. In some embodiments, it is about or at least about 2 times. In some embodiments, it is about or at least about 5 times. In some embodiments, it is about or at least about 10 times.

[0154] In some embodiments, the composition obtained after recovery is combined with the effluent composition of the ion exchange (IEX). In some embodiments, the effluent composition and / or the post-recovery wash composition are concentrated / further purified by evaporation to remove various solvents, for example, those having a lower boiling point than the diol compound. In some embodiments, the solvent (e.g., those solvents present in the IEX effluent composition and / or the post-recovery wash composition, such as water, methanol, ethanol, etc.) is removed by an evaporation process. In some embodiments, the evaporation is performed under reduced pressure. It is understood by those skilled in the art that various evaporation techniques exist and can be utilized in accordance with the present disclosure. In some embodiments, a composition containing about 30-95% (e.g., about 40-95%, 40-90%, 50%-90%, or 80%-95%; or about 30%, 40%, 50%, 60%, 70%, 80% or 90%) (w / w) of a diol compound (e.g., 1,6-hexanediol (HDO)) is obtained after evaporation. In some embodiments, a multiple-effect evaporation process optionally performed under vacuum is used. In some embodiments, evaporation removes water. In some embodiments, evaporation reduces the steam load in the distillation. In some embodiments, evaporation is performed under suitable conditions, under which there is little or no loss of the desired diol compound (such as 1,6-hexanediol (HDO)). As an alternative or supplement, distillation is performed to further concentrate / purify the diol compound, thereby obtaining a high-purity preparation.

[0155] In some embodiments, the technology provided includes refining. In some embodiments, refining removes salts and / or other impurities in a diol compound composition (e.g., 1,6-hexanediol (HDO) preparation) before distillation. In some embodiments, refining is performed after evaporation. As will be understood by those skilled in the art reading this disclosure, the evaporation of certain solvents (e.g., water) may result in the precipitation of certain salts, and / or the concentration of certain impurities (e.g., those impurities that may not be captured during the IEX process). In some embodiments, refining reduces the content of one or more salts and / or impurities. Refining can bring various benefits, improvements, and / or advantages. For example, in some embodiments, refining can provide better heating efficiency in distillation. In some embodiments, refining reduces or eliminates scaling, for example, scaling caused by the presence of salts in a reboiler. Refining can be performed using various techniques described herein. For example, in some embodiments, IEX resins are used. In some embodiments, activated carbon is used. In some embodiments, IEX resins are used as beds. In some embodiments, cation and anion exchange resins are used simultaneously. In some embodiments, the IEX resin is used as a mixed bed comprising cation and anion exchange resins. In some embodiments, the IEX for refining is or includes cation exchange. In some embodiments, the IEX for refining is or includes anion exchange. In some embodiments, the IEX for refining is or includes cation and anion exchange. Various IEX resins are as described herein. In some embodiments, the resin is a strong ion exchange resin. In some embodiments, the resin is a weak ion exchange resin.

[0156] Deodorization and decolorization

[0157] In some embodiments, a compound, such as a diol compound like 1,6-hexanediol (HDO), is provided in the form of a colorless liquid or solid. For example, in some embodiments, 1,6-hexanediol (HDO) is provided in the form of a colorless solid at room temperature. In some embodiments, a method includes removing an odor or color in a composition (e.g., a 1,6-hexanediol (HDO) formulation). In some embodiments, a method includes removing an odor. In some embodiments, a method includes removing a color. In some embodiments, a method includes removing an odor and a color. In some embodiments, a decolorization and / or deodorization step is included in the manufacturing process. Decolorization and deodorization can each independently be a single-step or multi-step process. In some embodiments, decolorization is a single step. In some embodiments, deodorization is a single step. In some embodiments, decolorization is a multi-step process. In some embodiments, deodorization is a multi-step process. In some embodiments, deodorization is a multi-step process. In some embodiments, decolorization and deodorization are performed simultaneously. In some embodiments, decolorization and deodorization are single-step processes.

[0158] Decolorization and / or deodorization can be performed independently at different stages. For example, in some embodiments, decolorization and / or deodorization are performed after the refining step and before distillation. In some embodiments, decolorization and / or deodorization are performed after the evaporation step and before distillation. In some embodiments, decolorization and / or deodorization are performed after the first distillation tower for removing low-boiling point compounds and before the second distillation tower where pure diol compounds (e.g., 1,6-hexanediol (HDO)) can be obtained. In some embodiments, after the purified diol compounds (e.g., 1,6-hexanediol (HDO)) are obtained in the second distillation tower, they are sent for decolorization and / or deodorization. In some embodiments, decolorization and deodorization are performed simultaneously, or one after another. In some embodiments, they are performed in multiple steps. In some embodiments, other steps are performed between them. For example, in some embodiments, deodorization is performed before the second distillation tower, while decolorization is performed after the second distillation tower, and vice versa.

[0159] According to the present disclosure, various techniques can be used for deodorization and / or decolorization. Some useful techniques are listed below as examples, such as hydrogenation, porous materials, etc. In some embodiments, contact with ion exchange (IEX) can remove certain odorous and / or colored substances. In some embodiments, the present disclosure includes one or more such techniques.

[0160] hydrogenation

[0161] In some embodiments, the provided methods include hydrogenation. In some embodiments, hydrogenation achieves deodorization and / or decolorization. In some embodiments, a composition (e.g., a diol compound preparation (e.g., 1,6-hexanediol (HDO) stream)) is reacted with hydrogen. In some embodiments, hydrogenation is carried out under conditions in the presence of a catalyst. In some embodiments, hydrogenation is carried out under conditions in the presence of a catalyst and pressurization. In some embodiments, hydrogenation is carried out under conditions in the presence of a catalyst and heating and pressurization.

[0162] In some embodiments, the catalyst is or comprises a metal. In some embodiments, the catalyst is or comprises a metal complex. In some embodiments, the catalyst is or comprises a metal oxide. In some embodiments, the metal is palladium. In some embodiments, the catalyst is or comprises palladium. In some embodiments, the catalyst is or comprises a palladium compound. In some embodiments, the catalyst is or comprises a palladium complex. In some embodiments, the metal is nickel. In some embodiments, the catalyst is Raney nickel. In some embodiments, the metal is platinum. In some embodiments, the catalyst comprises a combination of metals, metal oxides, or metal complexes.

[0163] In some embodiments, the catalyst is supported on a support structure. In some embodiments, the support structure is or comprises carbon. In some embodiments, the support structure is or comprises aluminum oxide. In some embodiments, the support structure is or comprises silicon dioxide. In some embodiments, the support structure is or comprises a combination of carbon, aluminum oxide and / or silicon dioxide.

[0164] In some embodiments, the reactor for hydrogenation is or comprises a packed bed configuration. In some embodiments, the packed bed is or comprises a random packing. In some embodiments, the packed bed is or comprises a structured packing. In some embodiments, the reactor is or comprises a fluidized bed configuration. In some embodiments, the reactor is a continuous stirred tank slurry reactor. In some embodiments, the reactor is or comprises a plug flow reaction configuration.

[0165] In some embodiments, the reaction pressure is about atmospheric pressure to about 300 bar. In some embodiments, the reaction pressure is about 1 to about 300 bar. In some embodiments, the hydrogen pressure is about 1 to about 300 bar, for example, about 1-250 bar, about 1-200 bar, about 1-150 bar, about 1-100 bar, about 1-50 bar, about 20-300 bar, about 30-300 bar, about 40-300 bar, about 50-300 bar, etc.

[0166] In some embodiments, the reaction temperature is from about ambient temperature to about 300° C. In some embodiments, the temperature is about 200-300° C., for example, about 25-300° C., about 30-300° C., about 40-300° C., about 50-300° C., about 25-250° C., about 25-200° C., about 25-150° C., about 25-100° C., etc.

[0167] As described herein, hydrogenation can be performed at different stages. For example, in some embodiments, the hydrogenation reaction is performed after removing heavy components (compounds having a boiling point higher than that of diol compounds (e.g., 1,6-hexanediol (HDO)), such as sugars, nitrogen-containing compounds, etc.). In some embodiments, hydrogenation after removing the heavy components has advantages such as reducing or preventing catalyst fouling. In some embodiments, hydrogenation is performed after the first distillation tower or after the second distillation tower, for example, for deodorization and / or decolorization. In some embodiments, hydrogenation is performed after the first distillation tower (e.g., if diol compounds (e.g., 1,6-hexanediol (HDO)) of sufficient purity are obtained through, for example, an intermediate fraction). In some embodiments, hydrogenation is performed after the second distillation tower. In some embodiments, the present disclosure includes evaluating impurities converted by hydrogenation.

[0168] Activated carbon

[0169] In some embodiments, the provided methods include contacting a composition (e.g., a diol compound preparation, such as a 1,6-hexanediol (HDO) preparation) with a porous material (e.g., activated carbon). In some embodiments, the porous material can be used for deodorization and / or decolorization. In some embodiments, the porous material is or comprises activated carbon. In some embodiments, the porous material adsorbs odor and / or color. According to the present disclosure, various porous materials (e.g., activated carbon) can be used.

[0170] In some embodiments, the composition (eg, diol compound preparation (eg, 1,6-hexanediol (HDO) stream)) is passed through an activated carbon bed. In some embodiments, activated carbon is added and a slurry is prepared, for example, in a suitable vessel such as a stirred tank.

[0171] Contact with a porous material (e.g., activated carbon) can be performed at different stages. For example, in some embodiments, contact is performed before distillation. In some embodiments, contact is performed before the first column distillation but before the next distillation step. In some embodiments, a diol compound composition (e.g., undistilled 1,6-hexanediol (HDO) preparation) is contacted with an activated carbon packed bed. According to the present disclosure, various conditions can be used. For example, in some embodiments, a pressure of about 1 bar to about 4 bar and / or a temperature of ambient temperature to about 80°C can be used. In some embodiments, contact is performed in a slurry composition. For example, in some embodiments, a diol compound composition (e.g., 1,6-hexanediol (HDO) preparation) is mixed at a pressure of about 1 bar to about 4 bar and / or a temperature of ambient temperature to about 80°C in a stirred reactor (e.g., a stirred tank reactor). In some embodiments, the slurry is filtered, for example, using a bag filter, a hydrocyclone filter, a vacuum drum filter, etc., to remove the activated carbon. In some embodiments, the activated carbon is removed by centrifugation.

[0172] In some embodiments, after distillation, contact is made with a porous material (e.g., activated carbon). In some embodiments, contact is made at the end to achieve final purification. According to the present disclosure, various techniques (e.g., the above-mentioned techniques) can be used. In some embodiments, a final product filter (e.g., a candle filter) is used, for example, to remove carbon powder and / or black matter.

[0173] High purity preparation

[0174] The present disclosure provides a technology capable of producing high-purity diol compound preparations, in particular high-purity long-chain diol compound preparations (e.g., diol compounds having at least 5 carbon atoms, such as having 5-12 carbon atoms), and / or in particular a technology capable of producing high-purity preparations from an initial aqueous preparation (thereby obtaining a high-purity aqueous preparation).

[0175] Various techniques, such as high performance liquid chromatography (HPLC), gas chromatography (GC) and / or ion chromatography (IC) can be used to evaluate the compositions described herein. For example, in some embodiments, high purity preparations are characterized by high performance liquid chromatography (HPLC), gas chromatography (GC) and / or ion chromatography (IC).

[0176] In some embodiments, the high purity formulation is an aqueous formulation; in some embodiments, the high purity formulation comprises water at a content greater than 50% and / or at a content not exceeding 99%.

[0177] In some embodiments, a high purity preparation of a particular diol compound of interest has a content level of about 1% to about 50% (w / w) of the compound in the preparation. In some embodiments, the content level is about 1% to about 45% (w / w). In some embodiments, the content level is about 1% to about 40% (w / w). In some embodiments, the content level is about 1% to about 35% (w / w). In some embodiments, the content level is about 1% to about 30% (w / w). In some embodiments, the content level is about 1% to about 25% (w / w).

[0178] In some embodiments, the content level is from about 1% to about 20% (w / w). In some embodiments, the content level is from about 1% to about 15% (w / w). In some embodiments, the content level is from about 1% to about 10% (w / w). In some embodiments, the content level is from about 1% to about 5% (w / w). In some embodiments, the content level is from about 10% to about 50% (w / w). In some embodiments, the content level is from about 20% to about 50% (w / w). In some embodiments, the content level is from about 30% to about 50% (w / w). In some embodiments, the content level is from about 40% to about 50% (w / w). In some embodiments, the content level is about 50% (w / w). In some embodiments, the content level is about 45% (w / w). In some embodiments, the content level is about 40% (w / w). In some embodiments, the content level is about 35% (w / w). In some embodiments, the content level is about 30% (w / w). In some embodiments, the content level is about 25% (w / w). In some embodiments, the content level is about 20% (w / w). In some embodiments, the content level is about 15% (w / w). In some embodiments, the content level is about 10% (w / w). In some embodiments, the content level is about 5% (w / w). In some embodiments, the content level is about 2% (w / w).

[0179] In some embodiments, in the high purity preparation, one or more ions (e.g., inorganic ions (e.g., sulfate, phosphate, pyruvate, lithium, sodium, potassium, ammonium, calcium, magnesium, ferrous, ferric, aluminum, chloride), organic ions (e.g., acetate, lactate, malate, succinate, maleate), amino acids (e.g., valine and / or leucine)) and / or impurity compounds are each independently absent (e.g., below the detection limit of various detection techniques) or, if present, are each independently at a low level. In some embodiments, the content level is about or no more than about 10000, 9000, 8000, 7000, 6000, 5000, 4000, 3000, 2000, 1000, 900, 800, 700, 600, 500, 400, 300, 200, 100, 90, 80, 70, 60, 50, 40, 30, 20, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, or 0.1 ppm (w / w unless otherwise indicated). In some embodiments, the content level is about or no more than about 10000 ppm. In some embodiments, the content level is about or no more than about 9000 ppm. In some embodiments, the content level is about or no more than about 8000 ppm. In some embodiments, the content level is about or no more than about 7000ppm. In some embodiments, the content level is about or no more than about 6000ppm. In some embodiments, the content level is about or no more than about 5000ppm. In some embodiments, the content level is about or no more than about 4000ppm. In some embodiments, the content level is about or no more than about 3000ppm. In some embodiments, the content level is about or no more than about 2000ppm. In some embodiments, the content level is about or no more than about 1000ppm. In some embodiments, the content level is about or no more than about 900ppm. In some embodiments, the content level is about or no more than about 800ppm. In some embodiments, the content level is about or no more than about 700ppm. In some embodiments, the content level is about or no more than about 600ppm. In some embodiments, the content level is about or no more than about 500ppm. In some embodiments, the content level is about or no more than about 400ppm. In some embodiments, the content level is about or no more than about 300ppm. In some embodiments, the content level is about or no more than about 200ppm. In some embodiments, the content level is about or no more than about 100 ppm. In some embodiments, the content level is about or no more than about 90 ppm. In some embodiments, the content level is about or no more than about 80 ppm. In some embodiments, the content level is about or no more than about 70 ppm.In some embodiments, the content level is about or no more than about 60ppm. In some embodiments, the content level is about or no more than about 50ppm. In some embodiments, the content level is about or no more than about 40ppm. In some embodiments, the content level is about or no more than about 30ppm. In some embodiments, the content level is about or no more than about 20ppm. In some embodiments, the content level is about or no more than about 10ppm. In some embodiments, the content level is about or no more than about 9ppm. In some embodiments, the content level is about or no more than about 8ppm. In some embodiments, the content level is about or no more than about 7ppm. In some embodiments, the content level is about or no more than about 6ppm. In some embodiments, the content level is about or no more than about 5ppm. In some embodiments, the content level is about or no more than about 4ppm. In some embodiments, the content level is about or no more than about 3ppm. In some embodiments, the content level is about or no more than about 2ppm. In some embodiments, the content level is about or no more than about 1ppm. In some embodiments, the content level is about or no more than about 0.9ppm. In some embodiments, the content level is about or no more than about 0.8ppm. In some embodiments, the content level is about or no more than about 0.7ppm. In some embodiments, the content level is about or no more than about 0.6 ppm. In some embodiments, the content level is about or no more than about 0.5 ppm. In some embodiments, the content level is about or no more than about 0.4 ppm. In some embodiments, the content level is about or no more than about 0.3 ppm. In some embodiments, the content level is about or no more than about 0.2 ppm. In some embodiments, the content level is about or no more than about 0.1 ppm. In some embodiments, the provided technology including pre-masking and / or post-recovery reduces the impurity and / or ion content to the same extent, not less than, or more than similar or other identical technologies without pre-masking and post-recovery.

[0180] For example, in some embodiments, the content level of chloride ions in the high purity preparation is about or no more than about 10000ppm. In some embodiments, it is about or no more than about 5000ppm. In some embodiments, it is about or no more than about 2000ppm. In some embodiments, it is about or no more than about 1000ppm. In some embodiments, it is about or no more than about 500ppm. In some embodiments, it is about or no more than about 200ppm. In some embodiments, it is about or no more than about 100ppm. In some embodiments, it is about or no more than about 50ppm. In some embodiments, it is about or no more than about 20ppm. In some embodiments, it is about or no more than about 10ppm. In some embodiments, it is about or no more than about 5ppm. In some embodiments, it is about or no more than about 1ppm. In some embodiments, it is about or no more than about 1ppm.

[0181] Additionally or alternatively, in some embodiments, the content level of sodium ions in the high purity preparation is about or no more than about 10000ppm. In some embodiments, it is about or no more than about 5000ppm. In some embodiments, it is about or no more than about 2000ppm. In some embodiments, it is about or no more than about 1000ppm. In some embodiments, it is about or no more than about 500ppm. In some embodiments, it is about or no more than about 200ppm. In some embodiments, it is about or no more than about 100ppm. In some embodiments, it is about or no more than about 50ppm. In some embodiments, it is about or no more than about 20ppm. In some embodiments, it is about or no more than about 10ppm. In some embodiments, it is about or no more than about 5ppm. In some embodiments, it is about or no more than about 1ppm. In some embodiments, it is about or no more than about 1ppm.

[0182] Additionally or alternatively, in some embodiments, the content level of potassium ions in the high purity preparation is about or no more than about 10000ppm. In some embodiments, it is about or no more than about 5000ppm. In some embodiments, it is about or no more than about 2000ppm. In some embodiments, it is about or no more than about 1000ppm. In some embodiments, it is about or no more than about 500ppm. In some embodiments, it is about or no more than about 200ppm. In some embodiments, it is about or no more than about 100ppm. In some embodiments, it is about or no more than about 50ppm. In some embodiments, it is about or no more than about 20ppm. In some embodiments, it is about or no more than about 10ppm. In some embodiments, it is about or no more than about 5ppm. In some embodiments, it is about or no more than about 1ppm. In some embodiments, it is about or no more than about 1ppm.

[0183] Additionally or alternatively, in some embodiments, the content level of magnesium ions in the high purity preparation is about or no more than about 10000ppm. In some embodiments, it is about or no more than about 5000ppm. In some embodiments, it is about or no more than about 2000ppm. In some embodiments, it is about or no more than about 1000ppm. In some embodiments, it is about or no more than about 500ppm. In some embodiments, it is about or no more than about 200ppm. In some embodiments, it is about or no more than about 100ppm. In some embodiments, it is about or no more than about 50ppm. In some embodiments, it is about or no more than about 20ppm. In some embodiments, it is about or no more than about 10ppm. In some embodiments, it is about or no more than about 5ppm. In some embodiments, it is about or no more than about 1ppm. In some embodiments, it is about or no more than about 1ppm.

[0184] Additionally or alternatively, in some embodiments, H2PO4 in a high purity preparation - 、HPO4 2- and / or PO4 3-The content level of ions is about or no more than about 10000ppm. In some embodiments, it is about or no more than about 5000ppm. In some embodiments, it is about or no more than about 2000ppm. In some embodiments, it is about or no more than about 1000ppm. In some embodiments, it is about or no more than about 500ppm. In some embodiments, it is about or no more than about 200ppm. In some embodiments, it is about or no more than about 100ppm. In some embodiments, it is about or no more than about 50ppm. In some embodiments, it is about or no more than about 20ppm. In some embodiments, it is about or no more than about 10ppm. In some embodiments, it is about or no more than about 5ppm. In some embodiments, it is about or no more than about 1ppm. In some embodiments, it is about or no more than about 1ppm.

[0185] Additionally or alternatively, in some embodiments, the content level of sulfate ions in the high purity preparation is about or no more than about 10000ppm. In some embodiments, it is about or no more than about 5000ppm. In some embodiments, it is about or no more than about 2000ppm. In some embodiments, it is about or no more than about 1000ppm. In some embodiments, it is about or no more than about 500ppm. In some embodiments, it is about or no more than about 200ppm. In some embodiments, it is about or no more than about 100ppm. In some embodiments, it is about or no more than about 50ppm. In some embodiments, it is about or no more than about 20ppm. In some embodiments, it is about or no more than about 10ppm. In some embodiments, it is about or no more than about 5ppm. In some embodiments, it is about or no more than about 1ppm. In some embodiments, it is about or no more than about 1ppm.

[0186] Additionally or alternatively, in some embodiments, the content level of pyruvate in the high purity preparation is about or no more than about 10000ppm. In some embodiments, it is about or no more than about 5000ppm. In some embodiments, it is about or no more than about 2000ppm. In some embodiments, it is about or no more than about 1000ppm. In some embodiments, it is about or no more than about 500ppm. In some embodiments, it is about or no more than about 200ppm. In some embodiments, it is about or no more than about 100ppm. In some embodiments, it is about or no more than about 50ppm. In some embodiments, it is about or no more than about 20ppm. In some embodiments, it is about or no more than about 10ppm. In some embodiments, it is about or no more than about 5ppm. In some embodiments, it is about or no more than about 1ppm. In some embodiments, it is about or no more than about 1ppm.

[0187] In some embodiments, the high purity formulation is characterized by a reduced concentration of one or more ions (e.g., inorganic ions (e.g., sulfate, phosphate, pyruvate, lithium, sodium, potassium, ammonium, calcium, magnesium, ferrous, ferric, aluminum, chloride), organic ions (e.g., acetate, lactate, malate, succinate, maleate), amino acids (e.g., valine and / or leucine)) and / or impurity compounds as compared to the ions and / or impurity compounds present in the initial aqueous formulation (e.g., the initial aqueous formulation used to prepare the high purity formulation) or the composition before ion exchange (the composition before ion exchange). In some embodiments, the high purity formulation is characterized by a reduced concentration of one or more of the following ions compared to the ions present in the initial aqueous formulation (e.g., the initial aqueous formulation used to prepare the high purity formulation): sulfate, phosphate, pyruvate, lithium, sodium, potassium, ammonium, calcium, magnesium, ferrous (II), ferric (III), aluminum, chloride, acetate, lactate, malate, succinate, maleate, valine, leucine. In some embodiments, the high purity formulation is characterized by a reduced concentration of chloride ions compared to the concentration of chloride ions present in the initial aqueous formulation (e.g., the initial aqueous formulation used to prepare the high purity formulation). In some embodiments, the high purity formulation is characterized by a reduced concentration of sodium ions compared to the concentration of sodium ions present in the initial aqueous formulation (e.g., the initial aqueous formulation used to prepare the high purity formulation). In some embodiments, the high purity formulation is characterized by a reduced concentration of potassium ions compared to the concentration of potassium ions present in the initial aqueous formulation (e.g., the initial aqueous formulation used to prepare the high purity formulation). In some embodiments, the high purity formulation is characterized in that the magnesium ion concentration is reduced compared to the magnesium ion concentration present in the initial aqueous formulation (e.g., the initial aqueous formulation used to prepare the high purity formulation). In some embodiments, the high purity formulation is characterized in that the sulfate ion concentration is reduced compared to the sulfate ion concentration present in the initial aqueous formulation (e.g., the initial aqueous formulation used to prepare the high purity formulation). In some embodiments, the high purity formulation is characterized in that the phosphate ion concentration is reduced compared to the phosphate ion concentration present in the initial aqueous formulation (e.g., the initial aqueous formulation used to prepare the high purity formulation). In some embodiments, the high purity formulation is characterized in that the pyruvate concentration is reduced compared to the pyruvate concentration present in the initial aqueous formulation (e.g., the initial aqueous formulation used to prepare the high purity formulation). In some embodiments, the concentration or content level is reduced by about or at least about 50%. In some embodiments, it is reduced by about or at least about 60%. In some embodiments, it is reduced by about or at least about 70%. In some embodiments, it is reduced by about or at least about 75%. In some embodiments, it is reduced by about or at least about 80%.In some embodiments, it is reduced by about or at least about 85%. In some embodiments, it is reduced by about or at least about 90%. In some embodiments, it is reduced by about or at least about 95%. In some embodiments, it is reduced by about or at least about 96%. In some embodiments, it is reduced by about or at least about 97%. In some embodiments, it is reduced by about or at least about 98%. In some embodiments, it is reduced by about or at least about 99%. In some embodiments, it is reduced by about or at least about 99.5%. In some embodiments, it is reduced by about or at least about 99.9% (for example, from 1000ppm to no more than 1ppm).

[0188] There are a variety of techniques available for assessing the content of ions, impurities, glycol compounds, etc., such as high performance liquid chromatography (HPLC), ion chromatography (IC), or gas chromatography (GC) coupled with ultraviolet detection (UV), mass spectrometry detection (MS), etc., and can be utilized in accordance with the present disclosure.

[0189] In some embodiments, the high-purity preparation is a commercial-scale preparation. In some embodiments, the high-purity preparation is a large-scale preparation, and its volume range is, for example, about 1kL to about 1000kL. In some embodiments, the volume is between about 10kL and about 800kL. In some embodiments, the volume is between about 10kL and about 600kL. In some embodiments, the volume is between about 10kL and about 400kL. In some embodiments, the volume is between about 10kL and about 200kL. In some embodiments, the volume is between about 10kL and about 100kL. In some embodiments, the volume is between about 10kL and about 80kL. In some embodiments, the volume is between about 10kL and about 70kL. In some embodiments, the volume is between about 10kL and about 60kL. In some embodiments, the volume is between about 10kL and about 50kL. In some embodiments, the volume is between about 10kL and about 40kL. In some embodiments, the volume is between about 10kL and about 30kL. In some embodiments, the volume is between about 10kL and about 20kL. In some embodiments, the volume is between about 10kL and about 15kL. In some embodiments, the volume is between about 20kL and about 800kL. In some embodiments, the volume is between about 50kL and about 800kL. In some embodiments, the volume is between about 100kL and about 800kL. In some embodiments, the volume is between about 300kL and about 800kL. In some embodiments, the volume is between about 500kL and about 800kL. In some embodiments, the volume is between about 20kL and about 100kL. In some embodiments, the volume is between about 30kL and about 80kL. In some embodiments, the volume is between about 40kL and about 70kL. In some embodiments, the volume is about 10kL, 20kL, 30kL, 40kL, 50kL, 60kL, 70kL or 80kL. In some embodiments, the volume is about 10kL. In some embodiments, the volume is about 20 kL. In some embodiments, the volume is about 30 kL. In some embodiments, the volume is about 40 kL. In some embodiments, the volume is about 50 kL. In some embodiments, the volume is about 60 kL. In some embodiments, the volume is about 70 kL. In some embodiments, the volume is about 80 kL. In some embodiments, the volume is about 90 kL. In some embodiments, the volume is about 100 kL. In some embodiments, the volume is about 200 kL. In some embodiments, the volume is about 300 kL. In some embodiments, the volume is about 400 kL. In some embodiments, the volume is about 500 kL. In some embodiments, the volume is about 600 kL. In some embodiments, the volume is about 700 kL. In some embodiments, the volume is about 800 kL.In some embodiments, the volume is about 900 kL. In some embodiments, the volume is about 1000 kL.

[0190] In some embodiments, high purity preparations are prepared by performing ion exchange (IEX) purification (eg, without further processing steps), as described herein.

[0191] In some embodiments, distillation techniques are used to remove certain impurities. For example, in some embodiments, distillation is used to remove impurities that have a lower boiling point than the diol compound at a specific pressure. In some embodiments, the diol compound is distilled to increase purity. In some embodiments, water is removed by distillation.

[0192] In some embodiments, the distillation technique used is thin film distillation. For example, in some embodiments, water is removed from a diol compound preparation (such as 1,6-hexanediol (HDO) preparation) using a thin film distillation apparatus at about 70°C. In some embodiments, the distillation is carried out under continuous feed operating conditions. In some embodiments, the water content in the composition (such as 1,6-hexanediol (HDO) preparation) is about or does not exceed about 500, 400, 300, 200, 100, 90, 80, 70, 60, 50, 40, 30, 20 or 10 ppm.

[0193] In some embodiments, distillation can be performed under different conditions to remove impurities with different properties (e.g., different boiling points at a specific pressure). For example, in some embodiments, water and / or other relatively low boiling impurities are first removed at a relatively low temperature (e.g., about 70° C.). Impurities with relatively high boiling points (e.g., higher than water but still lower than the target compound (e.g., 1,6-hexanediol (HDO)) are then removed at a relatively high temperature. For example, in some embodiments, a 1,6-hexanediol (HDO) composition is distilled so that the top of the distillation column is maintained at about 240° C. to remove impurities.

[0194] In some embodiments, after removing impurities, the compound is purified by distillation. For example, in some embodiments, the bottom temperature of the distillation tower is maintained at 260° C. to distill out 1,6-hexanediol (HDO). In some embodiments, the collected 1,6-hexanediol (HDO) is measured by high performance liquid chromatography (HPLC) and / or gas chromatography (GC) to have a purity of about 95% or higher (w / w).

[0195] It will be appreciated by those skilled in the art that various distillation techniques may be employed in light of the present disclosure. For example, in some embodiments, the distillation apparatus is equipped with an Aldershot tower. In some embodiments, the composition is continuously supplied to the distillation apparatus.

[0196] According to the present disclosure, various distillation techniques can be used. In some embodiments, the distillation method is continuous distillation. In some embodiments, the distillation method is batch distillation.

[0197] In some embodiments, the purity of the diol compound preparation is about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more (w / w). In some embodiments, the purity is about 90% or more. In some embodiments, the purity is about 91% or more. In some embodiments, the purity is about 92% or more. In some embodiments, the purity is about 93% or more. In some embodiments, the purity is about 94% or more. In some embodiments, the purity is about 95% or more. In some embodiments, the purity is about 96% or more. In some embodiments, the purity is about 97% or more. In some embodiments, the purity is about 98% or more. In some embodiments, the purity is about 99% or more. In some embodiments, the purity is about 99.5% or more.

[0198] product

[0199] The use of diol compounds described herein (eg, long chain diol compounds, such as diol compounds containing at least 5 carbon atoms (eg, 5-12 carbon atoms)) in various commercial fields is well known.

[0200] To name a few, 1,6-hexanediol (HDO) can be used to produce polyurethanes, coatings (e.g., automotive coatings), acrylates, adhesives, polyester resins, plasticizers, chemical probes (see, e.g., Kroschwald et al., “Hexanediol: a chemical probe to investigate the material properties of membrane-less compartments,” Matters 3(5), e201702000010; Sabari et al., “Coactivator condensation at super-enhancers links phase separation and gene control,” Science 2018 Jul 27;361(6400):eaar3958), etc. 1,5-Pentanediol can be used to produce polyester plastics, polyurethanes, various pharmaceuticals, inks and coatings, plasticizers, solvents, and industrial chemicals, etc. See, for example, Huber et al., US Department of Energy Bioenergy Technologies Office 2017 Project Peer Review.

[0201] In some embodiments, 1,6-hexanediol (HDO) is used to produce macrodiols such as adipates and polycarbonate diols for use in elastomers and polyurethane dispersions, such as for parquet flooring and leather coatings. 6-Hydroxycaproic acid can be cyclized to form ε-caprolactone, which can then be aminated to form ε-caprolactam, by conventional chemical methods, biosynthetic methods, or a combination of both. 6-Hydroxycaproic acid can be aminated to form 6-aminocaproic acid, which can then be cyclized to form ε-caprolactam, by conventional chemical methods, biosynthetic methods, or a combination of both. ε-Caprolactam can be used to produce nylon 6, a polymer that is widely used in many different industries. ε-Caprolactone can be polymerized to form polycaprolactone (PCL), a biodegradable polyester that has a variety of applications, including use in the production of specialty polyurethanes.

[0202] Various 2-ketocarboxylic acids can be used to prepare a variety of industrially relevant chemicals and pharmaceuticals.

[0203] In some embodiments, these chemicals and drugs or their intermediates are amino acids or α-hydroxycarboxylic acids. In some embodiments, the diol compound purified by the method described herein is used to make polyesters, polyester polyols, polyurethanes, nylons (e.g., made from adipic acid), polycarbonate diols (e.g., made from 1,6-hexanediol (HDO) or 1,5-pentanediol, etc.), diacrylates (e.g., made from 1,6-hexanediol (HDO) or 1,5-pentanediol, etc.), diglycidyl ethers (e.g., made from 1,6-hexanediol (HDO) or 1,5-pentanediol, etc.), etc.

[0204] In some embodiments, the high purity diol compound preparations described herein (e.g., long chain diol compounds, such as diol compounds containing at least 5 carbon atoms (e.g., 5-12 carbon atoms)) can be used to make lubricants, adhesives, polymers, textiles, coatings, fuels and fuel additives, and other value-added products.

[0205] The high-purity diol compound preparations of the present disclosure have a variety of advantages. For example, in some embodiments, their high purity can achieve efficient production, reduce product costs and / or produce high-purity products; alternatively or additionally, in some embodiments, when used to prepare polymers, the high-purity diol compound preparations of the present disclosure can produce polymers with a high degree of polymerization.

[0206] In some embodiments, the present disclosure provides the following embodiments as examples:

[0207] 1. A method for purifying an initial aqueous preparation comprising a diol compound,

[0208] wherein the diol compound has 5 to 12 carbon atoms, and

[0209] wherein the initial aqueous formulation comprises greater than 50% water; the method comprising:

[0210] The initial aqueous formulation is contacted with an ion exchange resin, wherein the resin is a hydrophilic resin.

[0211] 2. A method of purifying an initial aqueous preparation comprising a diol compound, comprising contacting the initial aqueous preparation with an ion exchange resin, wherein the matrix polymer of the resin is a hydrophilic polymer.

[0212] 3. The method of any of the preceding embodiments, wherein the hydrophilic resin is a polyacrylic acid resin.

[0213] 4. The method of embodiment 3, wherein the polyacrylic acid resin is a strong anion exchange resin.

[0214] 5. The method of embodiment 3, wherein the polyacrylic acid resin is a weak anion exchange resin.

[0215] 6. The method of embodiment 3, wherein the polyacrylic acid resin is a weak cation exchange resin.

[0216] 7. The method of any of the preceding embodiments, wherein the hydrophilic resin is a polymethacrylic acid resin.

[0217] 8. The method of embodiment 7, wherein the polyacrylic acid resin is a strong anion exchange resin.

[0218] 9. The method of embodiment 7, wherein the polyacrylic acid resin is a weak anion exchange resin.

[0219] 10. The method of embodiment 7, wherein the polyacrylic acid resin is a weak cation exchange resin.

[0220] 11. The method of any of the preceding embodiments, wherein the polymethacrylic acid resin is a polyacrylic acid resin.

[0221] 12. The method of embodiment 11, wherein the polyacrylic acid resin is a strong anion exchange resin.

[0222] 13. The method of embodiment 11, wherein the polyacrylic acid resin is a weak anion exchange resin.

[0223] 14. The method of embodiment 11, wherein the polyacrylic acid resin is a weak cation exchange resin.

[0224] 15. The method of any of the preceding embodiments, further comprising contacting the ion exchange resin with a pre-masking formulation comprising the diol compound prior to contacting the initial aqueous formulation with the ion exchange resin.

[0225] 16. A method of purifying an initial aqueous preparation comprising a diol compound, comprising contacting an ion exchange resin with a pre-masked preparation comprising the diol compound, and contacting the initial aqueous preparation with the pre-masked ion exchange resin.

[0226] 17. A method of purifying an initial aqueous preparation comprising a diol compound, comprising contacting an ion exchange resin with a pre-masked preparation comprising the diol compound, and contacting the initial aqueous preparation with the pre-masked ion exchange resin.

[0227] 18. The method of any of the preceding embodiments, further comprising contacting the ion exchange resin with a post-recovery solvent system after contacting the resin with the initial aqueous formulation.

[0228] 19. A method of purifying an initial aqueous preparation comprising a diol compound, comprising contacting the initial aqueous preparation with an ion exchange resin, and contacting the ion exchange resin with a post-recovery solvent system after contacting the initial aqueous preparation with the ion exchange resin.

[0229] 20. A method of purifying an initial aqueous preparation comprising a diol compound, comprising contacting an ion exchange resin with a pre-masked preparation comprising the diol compound, contacting the initial aqueous preparation with the pre-masked ion exchange resin, and contacting the ion exchange resin with a post-recovery solvent system after contacting the initial aqueous preparation with the pre-masked ion exchange resin.

[0230] 21. The method of any of the preceding embodiments, wherein the initial aqueous formulation comprises greater than about 50% water.

[0231] 22. The method according to any of the preceding embodiments, wherein the content of water in the formulation is in the range of 51% to 99%.

[0232] 23. The method of any of the preceding embodiments, wherein the initial aqueous formulation comprises greater than about 70% water.

[0233] 24. The method of any of the preceding embodiments, wherein the initial aqueous formulation comprises greater than about 90% water.

[0234] 25. The method of any of the preceding embodiments, wherein the initial aqueous formulation independently comprises one or more ions and / or impurities at an amount of about or at least about 50, 60, 70, 80, 90, 100, 150, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1500, 2000, 3000, 4000, 5000, 6000, 7000, 8000 or 10000 ppm (w / w).

[0235] 26. The method of any of the preceding embodiments, wherein the initial aqueous formulation comprises about or at least about 3000 ppm (w / w) of K + .

[0236] 27. The method of any of the preceding embodiments, wherein the initial aqueous formulation comprises about or at least about 90 ppm (w / w) Mg 2+ .

[0237] 28. The method of any of the preceding embodiments, wherein the initial aqueous formulation comprises about or at least about 3000 ppm (w / w) pyruvate.

[0238] 29. The method of any of the preceding embodiments, wherein the initial aqueous formulation comprises about or at least about 350 ppm (w / w) SO 2- .

[0239] 30. The method of any of the preceding embodiments, wherein the initial aqueous formulation comprises about or at least about 2000 ppm (w / w) of phosphate (H2PO4 - 、HPO4 2- and / or PO4 3- ).

[0240] 31. The method of any preceding embodiment, comprising contacting the initial aqueous formulation with an acidic resin.

[0241] 32. The method of any preceding embodiment, comprising contacting the initial aqueous formulation with a strongly acidic resin.

[0242] 33. The method of any preceding embodiment, comprising contacting the initial aqueous formulation with a weakly acidic resin.

[0243] 34. The method of any one of embodiments 31 to 33, wherein the base polymer of the resin is hydrophobic.

[0244] 35. The method of embodiment 34, wherein the resin is a polystyrene resin.

[0245] 36. The method of any one of embodiments 31 to 33, wherein the base polymer of the resin is hydrophilic.

[0246] 37. The method of embodiment 36, wherein the resin is a polyacrylic acid resin.

[0247] 38. The method of embodiment 36, wherein the resin is a polymethacrylic acid resin.

[0248] 39. The method of any one of embodiments 1 to 31, comprising contacting the initial aqueous formulation with a SK1BH resin.

[0249] 40. The method of any one of embodiments 1 to 31, comprising contacting the initial aqueous formulation with WK60L resin.

[0250] 41. The method of any one of embodiments 1 to 31, comprising contacting the initial aqueous formulation with WK10 resin.

[0251] 42. The method of any one of embodiments 31 to 41, wherein the resin is pretreated.

[0252] 43. The method of any one of embodiments 31 to 42, comprising contacting the ion exchange resin with a pre-masking formulation comprising the diol compound before contacting the ion exchange resin with the initial aqueous formulation.

[0253] 44. The method of any one of embodiments 31 to 42, comprising contacting the ion exchange resin with a post-recovery solvent system after contacting the ion exchange resin with the initial aqueous formulation.

[0254] 45. The method of any preceding embodiment, comprising contacting the initial aqueous formulation with a basic resin.

[0255] 46. ​​The method of any preceding embodiment, comprising contacting the initial aqueous formulation with a strongly basic resin.

[0256] 47. The method of any preceding embodiment, comprising contacting the initial aqueous formulation with a weakly basic resin.

[0257] 48. The method of any one of embodiments 45 to 47, wherein the base polymer of the resin is hydrophobic.

[0258] 49. The method of embodiment 48, wherein the resin is a polystyrene resin.

[0259] 50. The method of any one of embodiments 45 to 47, wherein the base polymer of the resin is hydrophilic.

[0260] 51. The method of embodiment 50, wherein the resin is a polyacrylic acid resin.

[0261] 52. The method of embodiment 50, wherein the resin is a polymethacrylic acid resin.

[0262] 53. The method of any one of embodiments 1 to 45, comprising contacting the initial aqueous formulation with a SCA10AOH resin.

[0263] 54. The method of any one of embodiments 1 to 45, comprising contacting the initial aqueous formulation with a WA21J resin.

[0264] 55. The method of any one of embodiments 1 to 45, comprising contacting the initial aqueous formulation with HPR4580Cl resin.

[0265] 56. The method of any one of embodiments 1 to 45, comprising contacting the initial aqueous formulation with a SCAV4Cl resin.

[0266] 57. The method of any one of embodiments 1 to 45, comprising contacting the initial aqueous formulation with an IRA67 resin.

[0267] 58. The method of any one of 45 to 57, wherein the resin is pretreated.

[0268] 59. The method of any one of embodiments 45 to 58, comprising contacting the ion exchange resin with a pre-masking formulation comprising the diol compound before contacting the ion exchange resin with the initial aqueous formulation.

[0269] 60. The method of any one of embodiments 45 to 59, comprising contacting the ion exchange resin with a post-recovery solvent system after contacting the ion exchange resin with the initial aqueous formulation.

[0270] 61. The method of any of the preceding embodiments, wherein the resin is characterized by an average degree of crosslinking in the range of 1% to 25%.

[0271] 62. The method of any of the preceding embodiments, wherein the resin is characterized by an average functional group density in the range of 0.1 to 4.0 (eq / L).

[0272] 63. The method of any of the preceding embodiments, wherein the resin is characterized by an average particle size in the range of 100 μm to 1500 μm.

[0273] 64. The method of any of the preceding embodiments, wherein the resin is characterized as Type 1 or Type 2.

[0274] 65. The method of any of the preceding embodiments, wherein the concentration of the diol compound in the pre-masking formulation is about or no more than about 50% (wt %) of the diol compound.

[0275] 66. The method of any of the preceding embodiments, wherein the concentration of the diol compound in the pre-masking formulation is about or no more than about 30% (wt %) of the diol compound.

[0276] 67. The method of any of the preceding embodiments, wherein the concentration of the diol compound in the pre-masking formulation is about or no more than about 20% (wt %) of the diol compound.

[0277] 68. The method of any of the preceding embodiments, wherein the concentration of the diol compound in the pre-masking formulation is about or no more than about 10% (wt %) of the diol compound.

[0278] 69. The method of any of the preceding embodiments, wherein the concentration of the diol compound in the pre-masking formulation is about or no more than about 5% (wt %) of the diol compound.

[0279] 70. The method of any of the preceding embodiments, wherein the concentration of the diol compound in the pre-masking formulation is about or no more than about 2% (wt %) of the diol compound.

[0280] 71. The method of any of the preceding embodiments, wherein the concentration of the diol compound in the pre-masking formulation is about or no more than about 0.1% to 2% (wt %) of the diol compound.

[0281] 72. The method of any of the preceding embodiments, wherein the concentration of the diol compound in the pre-masking formulation is about or no more than about 1% (wt %) of the diol compound.

[0282] 73. The method of any of the preceding embodiments, wherein the concentration of the diol compound in the pre-masking formulation is about or no more than about 0.3% to 0.7% (wt %) of the diol compound.

[0283] 74. The method of any of the preceding embodiments, wherein the concentration of the diol compound in the pre-masking formulation is about or no more than about 0.5% (wt %) of the diol compound.

[0284] 75. The method of any of the preceding embodiments, wherein the concentration of the diol compound in the pre-masking formulation is about or no more than about 0.2% (wt %) of the diol compound.

[0285] 76. The method of any of the preceding embodiments, wherein the concentration of the diol compound in the pre-masking formulation is about or no more than about 0.1% (wt %) of the diol compound.

[0286] 77. The method of any of the preceding embodiments, wherein for each contacting of the ion exchange resin with the pre-masking formulation, about or at least about 1 to 1000, such as about 1 to 500, 1 to 200, 1 to 100, 1 to 50, 1 to 20, 1 to 10, or about 1, 2, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 150, 200, 300, 400, 500, 600, 700, 800, 900 or 1000 milligrams of the diol compound are independently used per milliliter of resin.

[0287] 78. The method of embodiment 77, wherein about 1 to 50 mg of the diol compound is used per ml of resin.

[0288] 79. The method of embodiment 77, wherein about 20 mg of the diol compound is used per ml of resin.

[0289] 80. The method of any of the preceding embodiments, wherein for each pre-masked formulation, one or more ions or impurities are independently present at a lower level in the pre-masked formulation than in the initial aqueous formulation.

[0290] 81. The method of any of the preceding embodiments, wherein each pre-masked formulation is substantially free of one or more ions and / or impurities present in the initial aqueous formulation.

[0291] 82. The method of any of the preceding embodiments, wherein each pre-masked formulation is substantially free of all ions and / or impurities present in the initial aqueous formulation.

[0292] 83. The method according to any of the preceding embodiments, wherein the solvent of the pre-masked formulation is water.

[0293] 84. The method of any of the preceding embodiments, wherein for each contacting of the ion exchange resin with a post-recovery solvent system, about or at least about 1 to 100, such as about 1 to 50, 1 to 20, 1 to 10, 2 to 10, 5 to 10, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90 or 100 milliliters of post-recovery solvent system are independently used per 1 milliliter of resin.

[0294] 85. The method of any of the preceding embodiments, wherein for each contacting of the ion exchange resin with the post-recovery solvent system, about 1 to 10 ml of the post-recovery solvent system is independently used per 1 ml of resin.

[0295] 86. The process of any of the preceding embodiments, wherein the post-recovery solvent system comprises water.

[0296] 87. The process of any of the preceding embodiments, wherein the post-recovery solvent system comprises an alcohol.

[0297] 88. The process of any of the preceding embodiments, wherein the post-recovery solvent system comprises a short chain alcohol.

[0298] 89. The process of any of the preceding embodiments, wherein the post-recovery solvent system comprises methanol.

[0299] 90. The process of any of the preceding embodiments, wherein the post-recovery solvent system comprises ethanol.

[0300] 91. The process of any of the preceding embodiments, wherein the post-recovery solvent system comprises an organic solvent soluble in water.

[0301] 92. The process of any of the preceding embodiments, wherein the post-recovery solvent system comprises tetrahydrofuran (THF).

[0302] 93. The process of any of the preceding embodiments, wherein the post-recovery solvent system comprises acetone.

[0303] 94. The process of any one of embodiments 1 to 85, wherein the post-recovery solvent system is water.

[0304] 95. The process of any one of embodiments 1 to 85, wherein the post-recovery solvent system is an alcohol.

[0305] 96. The method of any one of embodiments 1 to 85, wherein the post-recovery solvent system is a short-chain alcohol.

[0306] 97. The process of any one of embodiments 1 to 85, wherein the post-recovery solvent system is methanol.

[0307] 98. The method of any one of embodiments 1 to 85, wherein the post-recovery solvent system is ethanol.

[0308] 99. The process of any one of embodiments 1 to 85, wherein the post-recovery solvent system is a mixture of two or more solvents selected from water and short-chain alcohols.

[0309] 100. The method of any of the preceding embodiments, wherein the total ion content of each post-recovery solvent system independently does not exceed about 1000, 900, 800, 700, 600, 500, 400, 300, 200, 100, 90, 80, 70, 60, 50, 40, 30, 20, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 ppm (wt / wt).

[0310] 101. The method of any of the preceding embodiments, wherein the total ion content of each post-recovery solvent system independently does not exceed about 100 ppm (wt / wt).

[0311] 102. The method of any of the preceding embodiments, wherein the total ion content of each post-recovery solvent system independently does not exceed about 10 ppm (wt / wt).

[0312] 103. The method of any of the preceding embodiments, wherein each post-recovery solvent system is substantially free of ions and compounds other than solvent.

[0313] 104. The method of any of the preceding embodiments, wherein for each contacting of the ion exchange resin with the post-recovery solvent system, about or at least about 1 to 100, such as about 1 to 50, 1 to 20, 1 to 10, 2 to 10, 5 to 10, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90 or 100 milliliters of solvent system (ml / ml) is used per 1 ml of resin.

[0314] 105. The method of embodiment 104, wherein for each contacting of the ion exchange resin with the post-recovery solvent system, about 1 to 20 ml of the solvent system is used per 1 ml of resin (ml / ml).

[0315] 106. The method of embodiment 104, wherein for each contacting of the ion exchange resin with the post-recovery solvent system, about 1 to 10 ml of the solvent system is used per 1 ml of resin (ml / ml).

[0316] 107. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, the concentration of one or more ions (e.g., inorganic ions such as sulfate, phosphate, pyruvate, lithium, sodium, potassium, ammonium, calcium, magnesium, ferrous, ferric, aluminum, chloride, and organic ions such as acetate, lactate, malate, succinate, maleate) independently does not exceed about 1000, 900, 800, 700, 600, 500, 400, 300, 200, 100, 90, 80, 70, 60, 50, 40, 30, 20, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, or 0.1 ppm (w / w).

[0317] 108. The method of any of the preceding embodiments, wherein the resin is in powder form.

[0318] 109. The method of any of the preceding embodiments, wherein the resin is spherical.

[0319] 110. The method of any of the preceding embodiments, wherein the resin is in film form.

[0320] 111. The process of any of the preceding embodiments, wherein the contacting with the resin is performed in a batch process.

[0321] 112. The method of any of the preceding embodiments, wherein the contacting with the resin is performed in a column.

[0322] 113. The process of any of the preceding embodiments, wherein the contacting with the resin is performed using a continuous flow process.

[0323] 114. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, the concentration of one or more ions (e.g., inorganic ions (such as sulfate, phosphate, pyruvate, lithium, sodium, potassium, ammonium, calcium, magnesium, ferrous, ferric, aluminum, chloride), and organic ions (such as acetate, lactate, malate, succinate, maleate)) independently does not exceed about 100 ppm (w / w).

[0324] 115. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, K + The concentration does not exceed 200ppm.

[0325] 116. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, K + The concentration does not exceed 100ppm.

[0326] 117. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, K + The concentration does not exceed 50ppm.

[0327] 118. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, K + The concentration does not exceed 20ppm.

[0328] 119. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, K + The concentration does not exceed 10ppm.

[0329] 120. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, K + The concentration does not exceed 5ppm.

[0330] 121. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, K + The concentration does not exceed 1ppm.

[0331] 122. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, K + The concentration does not exceed 0.5ppm.

[0332] 123. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, K is reduced compared to the initial aqueous formulation. + The content of is reduced by about or at least about 90%.

[0333] 124. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, K is reduced compared to the initial aqueous formulation. + The content of is reduced by about or at least about 99%.

[0334] 125. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, Mg 2+ The concentration does not exceed 200ppm.

[0335] 126. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, Mg 2+ The concentration does not exceed 100ppm.

[0336] 127. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, Mg 2+ The concentration does not exceed 50ppm.

[0337] 128. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, Mg 2+ The concentration does not exceed 20ppm.

[0338] 129. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, Mg 2+ The concentration does not exceed 10ppm.

[0339] 130. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, Mg 2+ The concentration does not exceed 5ppm.

[0340] 131. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, Mg 2+ The concentration does not exceed 1ppm.

[0341] 132. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, Mg 2+ The concentration does not exceed 0.5ppm.

[0342] 133. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, Mg 2+ The content of is reduced by about or at least about 90%.

[0343] 134. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, Mg 2+ The content of is reduced by about or at least about 99%.

[0344] 135. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, the concentration of pyruvate does not exceed 200 ppm.

[0345] 136. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, the concentration of pyruvate does not exceed 100 ppm.

[0346] 137. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, the concentration of pyruvate does not exceed 50 ppm.

[0347] 138. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, the concentration of pyruvate does not exceed 20 ppm.

[0348] 139. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, the concentration of pyruvate does not exceed 10 ppm.

[0349] 140. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, the concentration of pyruvate does not exceed 5 ppm.

[0350] 141. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, the concentration of pyruvate does not exceed 1 ppm.

[0351] 142. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, the concentration of pyruvate does not exceed 0.5 ppm.

[0352] 143. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, the pyruvate content is reduced by about or at least about 90% compared to the initial aqueous formulation.

[0353] 144. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, the pyruvate content is reduced by about or at least about 99% compared to the initial aqueous formulation.

[0354] 145. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, SO4 2- The concentration does not exceed 200ppm.

[0355] 146. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, SO4 2- The concentration does not exceed 100ppm.

[0356] 147. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, SO4 2- The concentration does not exceed 50ppm.

[0357] 148. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, SO4 2- The concentration does not exceed 20ppm.

[0358] 149. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, SO4 2- The concentration does not exceed 10ppm.

[0359] 150. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, SO4 2- The concentration does not exceed 5ppm.

[0360] 151. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, SO4 2- The concentration does not exceed 1ppm.

[0361] 152. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, SO4 2- The concentration does not exceed 0.5ppm.

[0362] 153. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, SO4 2- The content of is reduced by about or at least about 90%.

[0363] 154. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, SO4 2- The content of is reduced by about or at least about 99%.

[0364] 155. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, phosphate (H2PO4 - 、HPO4 2- and / or PO4 3- ) concentration does not exceed 200ppm.

[0365] 156. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, the phosphate (H2PO4 - 、HPO4 - 2- and / or PO4 3- ) concentration does not exceed 100ppm.

[0366] 157. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, phosphate (H2PO4 - 、HPO4 2- and / or PO4 3- ) concentration does not exceed 50ppm.

[0367] 158. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, phosphate (H2PO4 - 、HPO4 2- and / or PO4 3- ) concentration does not exceed 20ppm.

[0368] 159. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, phosphate (H2PO4 - 、HPO4 2- and / or PO4 3- ) concentration does not exceed 10ppm.

[0369] 160. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, the phosphate (H2PO4 - 、HPO4 2- and / or PO4 3- ) concentration does not exceed 5ppm.

[0370] 161. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, the phosphate (H2PO4 - 、HPO4 2- and / or PO4 3- ) concentration does not exceed 1ppm.

[0371] 162. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, the phosphate (H2PO4 - 、HPO4 2- and / or PO4 3- ) concentration does not exceed 0.5ppm.

[0372] 163. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, the phosphate (H2PO4 - 、HPO4 2- and / or PO4 3- ) is reduced by about or at least about 90%.

[0373] 164. The method of any of the preceding embodiments, wherein after contacting the initial aqueous formulation with the resin, the phosphate (H2PO4 - 、HPO4 2- and / or PO4 3- ) is reduced by about or at least about 99%.

[0374] 165. The method of any of the preceding embodiments, comprising preparing the initial aqueous formulation by fermentation.

[0375] 166. The method of any of the preceding embodiments, comprising deactivating the biomass.

[0376] 167. The method of any of the preceding embodiments, comprising preparing the initial aqueous formulation by fermentation, wherein said preparing comprises centrifugation.

[0377] 168. The method of any of the preceding embodiments, comprising preparing the initial aqueous formulation by fermentation, wherein said preparation comprises batch centrifugation.

[0378] 169. The method of any of the preceding embodiments, comprising preparing the initial aqueous formulation by fermentation, wherein said preparation comprises continuous centrifugation.

[0379] 170. The method of any of the preceding embodiments, comprising preparing the initial aqueous formulation by fermentation, wherein said preparing comprises filtration.

[0380] 171. The method of any of the preceding embodiments, comprising preparing the initial aqueous formulation by fermentation, wherein said preparation comprises microfiltration.

[0381] 172. The method of any of the preceding embodiments, comprising preparing the initial aqueous formulation by fermentation, wherein said preparation comprises nanofiltration.

[0382] 173. The method of any of the preceding embodiments, comprising membrane filtration.

[0383] 174. The method of any of the preceding embodiments, comprising membrane filtration, wherein the pore size is about 10 μm or less.

[0384] 175. The method of any of the preceding embodiments, comprising membrane filtration, wherein the filter membrane is in the shape of a flat sheet, a hollow tube fiber, a tube, a spiral, or a pleated shape.

[0385] 176. The method of any of the preceding embodiments, comprising evaporating water from the preparation obtained after contacting the initial aqueous preparation with an ion exchange resin.

[0386] 177. The method of any of the preceding embodiments, comprising evaporating water under vacuum from the preparation obtained after contacting the initial aqueous preparation with the ion exchange resin.

[0387] 178. The method of any of the preceding embodiments, further comprising distilling to remove components having a boiling point lower than the diol compound.

[0388] 179. The method of any of the preceding embodiments, comprising distilling the diol compound from the composition comprising the diol compound.

[0389] 180. The method according to any one of embodiments 178 to 179, wherein the distillation is performed under vacuum.

[0390] 181. The method of any preceding embodiment, comprising refining.

[0391] 182. The process of any of the preceding embodiments, comprising refining after evaporation and before distillation.

[0392] 183. The method of any of the preceding embodiments, wherein refining reduces the content of one or more salts.

[0393] 184. The method of any of the preceding embodiments, wherein refining comprises contacting with a cation exchange resin.

[0394] 185. The method of any of the preceding embodiments, wherein refining comprises contacting with an anion exchange resin.

[0395] 186. The method of any of the preceding embodiments, wherein refining comprises contacting with a porous material.

[0396] 187. The method of any of the preceding embodiments, wherein refining comprises contacting with activated carbon.

[0397] 188. The method of any of the preceding embodiments, comprising decolorizing the diol compound preparation.

[0398] 189. The method of any of the preceding embodiments, wherein decolorization comprises hydrogenation.

[0399] 190. The method of any of the preceding embodiments, wherein decolorizing comprises contacting with a porous material.

[0400] 191. The method of any of the preceding embodiments, wherein decolorization comprises contact with activated carbon.

[0401] 192. The method of any of the preceding embodiments, comprising deodorizing the diol compound formulation.

[0402] 193. The method of any of the preceding embodiments, wherein deodorizing comprises hydrogenation.

[0403] 194. The method of any of the preceding embodiments, wherein deodorizing comprises contacting with a porous material.

[0404] 195. The method of any of the preceding embodiments, wherein deodorizing comprises contacting with activated carbon.

[0405] 196. A diol compound preparation prepared by a process comprising the method of any preceding embodiment.

[0406] 197. A method for preparing a solvent, acrylate, polymer, polyurethane, polyester, adhesive, plasticizer or coating, comprising:

[0407] Providing a diol compound preparation according to embodiment 197,

[0408] The diol compound is converted into the solvent, acrylate, polymer, polyurethane, polyester, adhesive, plasticizer or coating.

[0409] 198. Use of the diol compound preparation of embodiment 197 in the preparation of solvents, acrylates, polymers, polyurethanes, polyesters, adhesives, plasticizers or coatings.

[0410] 199. A method of identifying a resin suitable for purifying an initial aqueous formulation comprising a diol compound, wherein:

[0411] The diol compound has 5 to 12 carbon atoms, and

[0412] wherein the initial aqueous formulation comprises greater than 50% water;

[0413] The method includes:

[0414] It is determined whether the particle size, crosslinking density, kind of functional group, functional group density, and hydrophilicity of the resin are within suitable or desired ranges, or have suitable or desired properties.

[0415] 200. A method of identifying a resin suitable for purifying an initial aqueous preparation comprising a diol compound, comprising using the resin in the method of any one of the preceding embodiments 1 to 200 and evaluating the loss of the diol compound during the ion exchange purification process.

[0416] 201. The method of any of the preceding embodiments, wherein the loss of diol compound during the ion exchange process does not exceed about 5%.

[0417] 202. The method of any of the preceding embodiments, wherein the loss of diol compound during the ion exchange process does not exceed about 4%.

[0418] 203. The method of any of the preceding embodiments, wherein the loss of diol compound during the ion exchange process does not exceed about 3%.

[0419] 204. The method of any of the preceding embodiments, wherein the loss of diol compound during the ion exchange process does not exceed about 2%.

[0420] 205. The method of any of the preceding embodiments, wherein the loss of diol compound during the ion exchange process does not exceed about 1%.

[0421] 206. The method of any one of embodiments 201 to 205, wherein the resin is determined to be suitable.

[0422] 207. The method of any of the preceding embodiments, wherein the loss of diol compound without pre-masking and pre-recovery is about or at least about 1.5, 2, 3, 4, 5, 6, 7, 8, 9 or 10 times the loss without pre-masking and without pre-recovery.

[0423] 208. The method of any of the preceding embodiments, wherein the loss of diol compound without pre-masking and pre-recovery is about or at least about twice the loss without pre-masking and pre-recovery.

[0424] 209. The method of any of the preceding embodiments, wherein the loss of diol compound without pre-masking and pre-recovery is about or at least about 5 times the loss without pre-masking and pre-recovery.

[0425] 210. The method of any of the preceding embodiments, wherein the loss of diol compound without pre-masking and pre-recovery is about or at least about 10 times the loss without pre-masking and pre-recovery.

[0426] 211. A method of identifying a resin suitable for purifying an initial aqueous formulation comprising a diol compound, wherein:

[0427] The diol compound has 5 to 12 carbon atoms, and

[0428] wherein the initial aqueous formulation comprises greater than 50% water;

[0429] The method includes:

[0430] contacting the resin with the initial aqueous formulation;

[0431] evaluating retention of diol compounds on the resin;

[0432] It was determined that the retention of diol compounds was reduced compared to that observed using hydrophobic resins under otherwise comparable conditions.

[0433] 212. A purified diol compound preparation, wherein the content of the diol compound is about at least about 50%-100%, greater than, or about, at least about, or about 2 times, 3 times, 4 times, 5 times, 6 times, 7 times, 8 times, 9 times, 10 times, 11 times, 12 times, 13 times, 14 times, 15 times, 16 times, 17 times, 18 times, 19 times, 20 times, 30 times, 40 times, 50 times or 100 times the content of the diol compound in the initial aqueous preparation from which the diol compound was purified.

[0434] 213. A purified preparation of a diol compound wherein the pyruvate content is at least 10 times lower than the pyruvate content in the aqueous preparation from which the diol compound was purified.

[0435] 214. A purified diol compound preparation wherein the phosphate content is at least 10 times lower than the phosphate content in the initial aqueous preparation from which the diol compound was purified.

[0436] 215. A purified diol compound preparation wherein the sulfate content is at least 10 times lower than the sulfate content in the initial aqueous preparation from which the diol compound was purified.

[0437] 216. A purified diol compound preparation wherein the potassium ion content is at least 10 times lower than the potassium ion content in the initial aqueous preparation from which the diol compound was purified.

[0438] 217. A purified diol compound preparation wherein the amount of magnesium ions is at least 10 times less than the amount of magnesium ions in the initial aqueous preparation from which the diol compound was purified.

[0439] 218. The method or formulation of any preceding embodiment, wherein the diol compound has from about 5 to 12 carbon atoms.

[0440] 219. The method or formulation of any one of embodiments 1 to 218, wherein the diol compound has L(OH) n The structure of wherein L is a hydrocarbon moiety containing 5 to 12 carbon atoms, and n is 2 or 3.

[0441] 220. The method or formulation of any one of embodiments 1 to 218, wherein the diol compound has L(OH) n The structure of wherein L is a hydrocarbon moiety containing 5 to 8 carbon atoms, and n is 2 or 3.

[0442] 221. The method or formulation of any preceding embodiment, wherein n is 2.

[0443] 222. The method or formulation of any preceding embodiment, wherein L is linear.

[0444] 223. The method or formulation of any one of embodiments 1 to 221, wherein L is branched.

[0445] 224. The method or formulation of any preceding embodiment, wherein L is saturated.

[0446] 225. The method or formulation of any one of embodiments 1 to 223, wherein L is partially unsaturated.

[0447] 226. The method or formulation of any one of embodiments 1 to 219, wherein the diol compound has HO(CH2) m The structure of OH wherein m is 5 to 12.

[0448] 227. The method or formulation of any one of embodiments 1 to 219, wherein the diol compound has HO(CH2) m The structure of OH wherein m is 5 to 8.

[0449] 228. The method or formulation of any one of embodiments 1 to 219, wherein the diol compound is HO(CH2)5OH.

[0450] 229. The method or formulation of any one of embodiments 1 to 219, wherein the diol compound is HO(CH2)6OH.

[0451] 230. The method or formulation of any one of embodiments 1 to 219, wherein the diol compound is HO(CH2)7OH.

[0452] 231. The method or formulation of any one of embodiments 1 to 219, wherein the diol compound is HO(CH2)8OH.

[0453] 232. The method or formulation of any one of embodiments 1 to 219, wherein the diol compound is HO(CH2)9OH.

[0454] 233. The method or formulation of any one of embodiments 1 to 219, wherein the diol compound is HO(CH2) 10 OH.

[0455] 234. The method or formulation of any one of embodiments 1 to 219, wherein the diol compound is HO(CH2) 11 OH.

[0456] 235. The method or formulation of any one of embodiments 1 to 219, wherein the diol compound is HO(CH2) 12 OH.

[0457] Example

[0458] Example 1: Exemplary Filtration Process

[0459] A step in purifying a chemical (in this case, a diol compound) from a fermentation broth may begin with centrifugation and / or filtration to physically exclude insoluble materials and large molecules. Reducing the pore size of the filtration will further improve the purity of the permeate, but there will still be some chemical components in the aqueous preparation that cannot be separated by size. Electrostatic properties, amplified by adjusting the pH, can be used to separate cations and anions from each other. Certain ionic compounds may preferentially bind to insoluble support structures (e.g., ion exchange resins).

[0460] For example, in some embodiments, it may be desirable to perform one or more filtration steps, particularly when the starting preparation contains one or more species that are amenable to size separation relative to the diol compound of interest.

[0461] In certain embodiments (particularly including those in which certain diol compounds of interest are produced by fermentation such that the aqueous preparation comprises cells or cellular components), it may be desirable to perform one or more microfiltration and / or nanofiltration steps.

[0462] This example describes certain steps in the provided methods for purifying a diol compound from a fermentation broth containing the diol compound.

[0463] The overall scheme of some embodiments adopted is shown graphically in Figure 1 In the figure, it is shown that an aqueous preparation (specifically, a fermentation broth) containing a diol compound (specifically, a higher fatty alcohol compound, specifically 1,6-hexanediol (HDO) in this example) is first treated with tangential flow filtration (TFF) and / or centrifugation. In some embodiments, two stages of tangential flow filtration are used: microfiltration (MF) and nanofiltration (NF). Each of these filtration steps uses a polymer membrane to separate the target molecule (HDO) from impurities in the fermentation broth by size separation.

[0464] The fermentation broth is produced by culturing an E. coli strain in a medium containing a phosphate buffer, a metal salt, an amino acid, and a carbon source (glycerol). The cells are cultured in a bioreactor (e.g., in some embodiments, to a commercial scale of 10 kL or greater as described herein) until their optical density (OD) exceeds 100. The entire fermentation broth is then diluted with deionized water to a cell optical density of 50. Commercially available 1,6-hexanediol is added to the fermentation broth at a concentration of 20 g / L or 100 g / L to provide samples for testing.

[0465] Insoluble materials were removed from the fermentation broth by tangential flow filtration (TFF). The fermentation broth was first subjected to microfiltration (0.1 μm polyvinylidene fluoride (PVDF), polyvinylidene fluoride (PVDF) with a molecular weight cutoff (MWCO) of 800 kDa) and then to nanofiltration (150-300 Da polyamide (PA), 300-500 Da polyamide (PA)).

[0466] As shown in the figure, microfiltration is used to retain suspended cell aggregates and most cell debris while allowing the rest of the material to pass through. Microfiltration can cover a range of membrane pore sizes or molecular weight cutoffs (MWCO), for example, from 100-800 kDa. Typically, microfiltration aims to reduce the amount of solid cell aggregates (quantified by optical density, cell packing volume, or dry cell weight) while not retaining any 1,6-hexanediol (quantified by high performance liquid chromatography (HPLC)). Especially for large-scale separations, it may be desirable to maximize the membrane flux of this microfiltration step.

[0467] As shown in the figure, nanofiltration is used to allow 1,6-hexanediol and other smaller molecules to pass through (metal ions, monomeric sugars, small organic acids, etc.) while retaining larger molecules (small cell debris, proteins, dimers and larger sugars, large organic acids, etc.). Nanofiltration also covers a range of molecular weight cutoffs, ranging from 200Da to 3kDa. Typically, nanofiltration is designed to reduce impurities (e.g., as quantified by HPLC and / or conductivity) while not retaining 1,6-hexanediol (e.g., as quantified by HPLC). Especially for large-scale separations, it may be desirable to maximize the membrane flux of this nanofiltration step.

[0468] Microfiltration and nanofiltration were tested on two membranes:

[0469] Microfiltration: 0.1 μm PVDF, 800 kDa MWCO PVDF

[0470] Nanofiltration: 150-300Da polyamide (PA), 300-500Da polyamide (PA; other materials such as polysulfone, cellulose, etc. are also possible).

[0471] The main indicators used to evaluate separation efficiency include: (1) the degree of optical density reduction, (2) the retention rate of impurities, and (3) the retention rate of 1,6-hexanediol (HDO). In this case, the retention rate is used instead of the yield because the yield takes into account the losses caused by system and operation peculiarities (e.g., hold-up volume, losses during loading / unloading, dilution, and losses due to operator error). The present disclosure provides insight that the retention rate can more accurately reflect the interaction of 1,6-hexanediol with the membrane. For microfiltration and nanofiltration, the theoretical ideal retention rate is zero because the retention of 1,6-hexanediol will result in a loss of yield. The retention rate is defined as:

[0472]

[0473] The retention of 1,6-hexanediol by various membranes demonstrates the efficiency of the filtration process by retaining insoluble matter.

[0474] Table 1. Under consistent operating conditions, all membranes showed low rejection of 1,6-hexanediol.

[0475] Feed concentration (g / L) Feed concentration (g / L) Feed concentration (%) 0.1μm microfiltration 18.21 17.98 1.3％ 800kDa Microfiltration 19.79 19.17 3.13％ 150-300Da Nanofiltration 16.28 15.64 3.93％ 200-400Da Nanofiltration 17.98 17.95 0.17％

[0476] The 0.1 μm filter allows a small amount of suspended solids to pass into the permeate stream, while the 800 kDa filter effectively removes all suspended solids.

[0477] Table 2. Reduction in optical density (OD) after microfiltration

[0478] Microfiltration pore size Feed optical density Optical density of permeate Retention rate (%) 0.1μm 50 1.1 97.8 800kDa 50 0.10 99.8

[0479] In some embodiments, the microfiltration membrane does not reduce conductivity. In some embodiments, the nanofiltration membrane reduces conductivity (μS / cm), in some cases by about 65%.

[0480] Table 3. Conductivity reduction (all values ​​are in μS / cm unless otherwise stated)

[0481] Feed solution Penetrant Retentate Conductivity reduction rate (%) 0.1μm microfiltration 6615 6687 6900 0％ 800kDa Microfiltration 9648 9170 8694 ~0% (considering dilution factor) 300-500Da Nanofiltration 8694 2909 17630 66.5％ 150-300Da Nanofiltration 3365 1220 8478 63.7％

[0482] In some embodiments, a 0.1 μm membrane has a higher flux than an 800 kDa membrane over a range of transmembrane pressures.

[0483] Table 4. Transmembrane pressure (TMP) and flux of 0.1 μm and 800 kDa microfiltration

[0484]

[0485]

[0486] In some embodiments, a 150-300 Da membrane has a higher flux than a 300-500 Da membrane over a range of transmembrane pressures.

[0487] Table 5. Transmembrane pressure (TMP) and flux of 150-300Da and 300-500Da nanofiltration

[0488] Transmembrane pressure (psi) <![CDATA[300 - 500Da flux (L / m 2 / h)]]> <![CDATA[150 - 300 Da flux (L / m 2 / h)]]> 100 5.65 8.63 150 12.26 19.13 200 17.42 25.86 250 21.29 34.5 270 23.87 37.5

[0489] The operating conditions are varied to assess the permeate flux. For microfiltration, the applied transmembrane pressure is between 35 psi and 80 psi. For nanofiltration, the applied transmembrane pressure is between 100 psi and 350 psi. The transmembrane pressure (TMP) is a pressure reading that takes into account the pressure drop across the membrane and across the membrane and is defined here as:

[0490]

[0491] The permeate flux is expressed as the permeate flow rate normalized by the membrane area. In some embodiments, the surface area of ​​the microfiltration membrane is 0.15 square meters and the surface area of ​​the nanofiltration membrane is 0.35 square meters. All conditions are operated under total reflux (the retentate is continuously sent back to the feed tank). This example demonstrates, for example:

[0492] (1) When evaluating and / or utilizing filtration techniques (e.g., in the context of diol compound separations described herein, such as separations of long-chain diol compounds, particularly in aqueous formulations, etc.), assessing the "retention" level (i.e., the amount of target material that does not pass through the filter) is a particularly useful parameter.

[0493] (2) In some useful technical embodiments, it is not necessary to use 0.1 μm microfiltration.

[0494] (3) In some useful technical embodiments, nanofiltration may be more useful than microfiltration.

[0495] (4) In some embodiments, membrane filtration of 150-300 Da may be particularly useful.

[0496] More specifically, this example demonstrates that both sets of membranes are viable for the separation of diol compounds (e.g., HDO) (e.g., as an initial separation step applied to aqueous formulations such as aqueous fermentation broths). Specifically, the results show that diol compounds such as HDO are not significantly retained (i.e., a large portion passes through the membrane) by any of the four membranes considered.

[0497] The present results further demonstrate that an 800 kDa microfilter is capable of adequate or complete removal of solid matter (e.g., as determined by high performance liquid chromatography (HPLC) and / or optical density measurement at 600 nm and / or 660 nm) with only a moderate reduction in flux; the present disclosure teaches that in certain embodiments, it is desirable to use an 800 kDa microfilter (e.g., particularly useful in the treatment of fermentation broth preparations or other preparations derived therefrom). The present disclosure also teaches that using a 150-300 Da filter in nanofiltration can achieve higher flux and comparable conductivity reduction effects compared to other filters; the present disclosure teaches that in certain embodiments, using a 150-300 Da filter for nanofiltration (e.g., particularly useful in the treatment of fermentation broth preparations or other preparations derived therefrom).

[0498] In some embodiments, alternative or additional cell removal methods may be used, such as dead-end filtration (filter press, leaf filter, etc.), centrifugation (decanter, decanter centrifuge, etc.). In some embodiments, continuous centrifugation may be used. In some embodiments, the continuous centrifugation is a cage centrifugation. In some embodiments, the continuous centrifugation is a disk centrifugation. In some embodiments, the continuous centrifugation is a nozzle centrifugation. Other initial separation methods may also be feasible, such as solvent extraction or fixed bed adsorption.

[0499] Example 2: Exemplary Ion Exchange Techniques

[0500] This example documents some of the surprising discoveries provided by the present disclosure:

[0501] (i) contacting the diol compound with a chromatographic resin (e.g., an ion exchange resin) prior to separating the diol compound from a sample (e.g., from an aqueous sample, such as an initial aqueous formulation described herein) using the resin increases the efficiency of purification achieved by the resin. That is, more of the diol compound will pass through the resin that has been pretreated as described herein than through an otherwise similar resin that has not been pretreated as described herein; and

[0502] (ii) washing the chromatographic resin to which the diol compounds described herein (e.g., long-chain diol compounds from aqueous preparations) have been adsorbed with a solvent system (e.g., water, alcohols (e.g., short-chain alcohols such as methanol and ethanol), suitable organic solvents (e.g., tetrahydrofuran and acetone), or a mixture of two or more such solvents) can effectively remove diol compound species from the resin, and in certain embodiments, removes diol compound species to a greater extent than non-diol compounds.

[0503] In some embodiments, the following process is performed:

[0504] (i) "IEX-I" (reference process; "conventional comparative example")

[0505] (a) 40 mL of pretreated resin was treated with 200 mL of simulated solution for 1 hour. The resin was separated by filtration and the filtrate was analyzed by high performance liquid chromatography (HPLC). The loss of 1,6-hexanediol (HDO) was evaluated.

[0506] (ii) “IEX-II” (pre-masking + post-recovery)

[0507] (a) 40 mL of the pretreated resin was treated with 0.5% aqueous HDO solution (150 g) for 30 minutes with stirring (pre-masking), and then the resin was recovered by filtration. The filtrate was analyzed by high performance liquid chromatography (HPLC). The loss of HDO was evaluated.

[0508] (b) The recovered resin was treated with 200 mL of the simulated solution under stirring for 1 hour. The resin was recovered by filtration and the filtrate was analyzed by high performance liquid chromatography (HPLC). The loss of HDO was evaluated.

[0509] (c) The recovered resin was treated with water (200 mL) by stirring for 1 hour (post-recovery). The resin was separated by filtration and the filtrate was analyzed by high performance liquid chromatography (HPLC). The amount of HDO recovered was evaluated.

[0510] (iii) "IEX-III" (pre-masking only)

[0511] (a) 40 mL of the pretreated resin was treated with 0.5% aqueous HDO solution (150 g) for 30 minutes with stirring (pre-masking), and then the resin was recovered by filtration. The filtrate was analyzed by high performance liquid chromatography (HPLC). The loss of HDO was evaluated.

[0512] (b) The recovered resin was treated with 200 mL of the simulated solution under stirring for 1 hour. The resin was recovered by filtration and the filtrate was analyzed by high performance liquid chromatography (HPLC). The loss of HDO was evaluated.

[0513] (iv) “IEX-IV” (post-recovery)

[0514] (a) 40 mL of pretreated resin was stirred with 200 mL of simulated solution for 1 hour. The resin was recovered by filtration and the filtrate was analyzed by high performance liquid chromatography (HPLC). The loss of HDO was evaluated.

[0515] (b) The recovered resin was treated with water (200 g) by stirring for 1 hour (post-recovery). The resin was separated by filtration and the filtrate was analyzed by high performance liquid chromatography (HPLC). The amount of HDO recovered was evaluated.

[0516] Diol compound loss analysis and quantification Each sampled solution was analyzed by high performance liquid chromatography (HPLC) and ion chromatography (IC).

[0517]

[0518] In some embodiments, the total HDO loss rate is calculated as follows (can also be used for other diol compounds):

[0519]

[0520] The total HDO loss during the ion exchange process = the HDO loss caused by ion exchange + the HDO loss caused by pre-masking (if pre-masking is performed) - the HDO amount recovered by post-recovery (if post-masking is performed).

[0521] Simulated solution A was designed to simulate the fermentation broth after microfiltration and nanofiltration. Phosphate, sulfate, and pyruvate as a group of undesirable anions and potassium and magnesium as a group of undesirable cations were to be purified from the aqueous preparation of 1,6-hexanediol.

[0522] Table 6. Simulated solution A

[0523] Compound Concentration / wt% 1,6-Hexanediol (HDO) 1.50 <![CDATA[K3PO4]]> 0.75 <![CDATA[MgSO4]]> 0.05 Pyruvate 0.35 Ion exchange water ー

[0524] This example demonstrates the effectiveness of pre-masking and / or post-recovery in minimizing the loss of separation target when using various ion exchange resins. Unless otherwise stated, concentrations after ion exchange (IEX) generally refer to the effluent concentration of the ion exchange, and ppm refers to weight ratio (w / w).

[0525] Table 7. Some results of strong cation exchange resin, polystyrene (SK1BH) Mitsubishi DIAION

[0526] Total HDO loss rate / wt% <![CDATA[K + / ppm]]> <![CDATA[Mg 2+ / ppm]]> Simulated solution A - 3100 91 IEX-I 11.1 140 0.8 IEX-II 0.635 143 1.0 IEX-III 8.47 151 1.2 IEX-IV 1.14 135 0.9

[0527] Table 8. Some results for strong anion exchange resin, polystyrene (SA10AOH) Mitsubishi DIAION

[0528] Total HDO loss rate / wt% Pyruvic acid / ppm <![CDATA[SO4 2- / ppm]]> <![CDATA[PO4 3- / ppm]]> Simulated solution A - 3200 350 2400 IEX-I 13.4 53 25 0 IEX-II 4.07 51 21 0 IEX-III 11.7 53 20 0 IEX-IV 6.33 61 23 0

[0529] In some embodiments, it was observed that weak, hydrophobic anion exchange resins did not perform as well as other ion exchange resins.

[0530] Table 9. Some results of weak anion exchange resin, polystyrene (WA21J) Mitsubishi DIAION

[0531]

[0532] This example demonstrates that hydrophilic anion exchange resins are very effective in adsorbing unwanted anions from an initial aqueous preparation while minimizing the loss of separation targets. In some embodiments, the hydrophilic anion exchange resins adsorb little of the desired separation target from the initial aqueous preparation and then preferentially release the material substantially free of inorganic anion contaminants. In some embodiments, when a post-recovery wash operation is performed, the loss is reduced by more than 50%.

[0533] Table 10. Certain results for strong anion exchange resin, polyacrylic acid type (HPR4850Cl) AmberLite DuPont.

[0534] Total HDO loss rate / wt% Pyruvic acid / ppm <![CDATA[SO4 2- / ppm]]> <![CDATA[PO4 3- / ppm]]> Simulated solution A - 3200 350 2400 IEX-I 0.693 100 4.4 1.8 IEX-II 0.341 110 4.7 1.1 IEX-III 0.684 103 4.7 1.5 IEX-IV 0.338 102 4.7 1.8

[0535] Table 11. Certain results for strong anion exchange resin, polyacrylic acid type (SCAV4Cl) AmberLite DuPont.

[0536] Total HDO loss rate / wt% Pyruvic acid / ppm <![CDATA[SO4 2- / ppm]]> <![CDATA[PO4 3- / ppm]]> Simulated solution A - 3200 350 2400 IEX-I 0.664 180 6.4 3.6 IEX-II 0.289 178 6.1 3.1 IEX-III 0.661 183 6.8 3.5 IEX-IV 0.297 177 7.1 3.2

[0537] This example demonstrates that hydrophilic polyacrylic acid resins, when treated with appropriate pre-masking and / or post-recycling, have greatly improved performance in the selective removal of unwanted cationic contaminants.

[0538] Table 12. Some results for weak cation exchange resin, polyacrylic acid type (WK60L) Mitsubishi Relite.

[0539] Total HDO loss rate / wt% <![CDATA[K + / ppm]]> <![CDATA[Mg 2+ / ppm]]> Simulated solution A - 3100 91 IEX-I 5.92 210 1.2 IEX-II 0.01 225 1.5 IEX-III 2.24 241 2.1 IEX-IV 0.22 203 1.8

[0540] This example demonstrates that pre-masking of a hydrophilic resin can reduce adsorption losses of diol compound separation targets while still effectively removing unwanted anions.

[0541] Table 13. Some results for weak anion exchange resin, polyacrylic acid type (IRA67) AmberLite DuPont.

[0542] Total HDO loss rate / wt% Pyruvic acid / ppm <![CDATA[SO4 2- / ppm]]> <![CDATA[PO4 3- / ppm]]> Simulated solution A - 3200 350 2400 IEX-I 2.18 240 15.8 7.9 IEX-II 1.13 251 13.7 8.0 IEX-III 1.91 248 14.2 7.4 IEX-IV 1.57 257 14.9 7.6

[0543] This example demonstrates that pre-masking and / or post-recovery of less hydrophilic resins can reduce losses during ion exchange.

[0544] Table 14. Some results for weak cation exchange resin, polymethacrylic acid type (WK10) Mitsubishi DIAION.

[0545] Total HDO loss rate / wt% <![CDATA[K + / ppm]]> <![CDATA[Mg 2+ / ppm]]> Simulated solution A - 3100 91 IEX-I 3.28 219 1.9 IEX-II 0.25 243 3.4 IEX-III 1.71 238 3.7 IEX-IV 0.71 214 2.6

[0546] The use of other diol compounds also demonstrates the advantages and benefits of the provided technology.

[0547] Table 15. Simulated solution B

[0548] Compound Concentration (wt%) 1,4-Butanediol (BDO) 1.50 <![CDATA[K3PO4]]> 0.75 <![CDATA[MgSO4]]> 0.05 Pyruvate 0.35 Ion exchange water ー

[0549] This example demonstrates that pre-masking and / or post-recycling can reduce the loss of 1,4-butanediol (BDO).

[0550] Table 16. Some results for strong cation exchange resin, polystyrene (SK1BH) Mitsubishi DIAION.

[0551] Total BDO loss rate / wt% <![CDATA[K + / ppm]]> <![CDATA[Mg 2+ / ppm]]> Simulated solution B - 3100 91 IEX-I 1.05 134 1.8 IEX-II 0.335 136 1.3 IEX-III 0.870 145 1.9 IEX-IV 0.531 130 0.9

[0552] Table 17. Simulated Solution C.

[0553] Compound Concentration (wt%) 1,8-Octanediol (ODO) 1.50 <![CDATA[K3PO4]]> 0.75 <![CDATA[MgSO4]]> 0.05 Pyruvate 0.35 Ion exchange water -

[0554] This example demonstrates that pre-masking and / or post-recovery can reduce the loss of 1,8-octanediol (ODO). In some embodiments, as the carbon chain grows, the loss of diol compounds and / or the adsorption capacity of the resin increases. As shown herein, pre-masking and / or post-recovery can greatly reduce the loss of the desired diol.

[0555] Table 18. Some results for strong cation exchange resin, polystyrene (SK1BH) Mitsubishi DIAION.

[0556]

[0557]

[0558] This example demonstrates that the resin may have a preferential adsorption effect on longer chain alkyl glycol compounds. In some embodiments, the loss of long chain glycol compounds is higher than that of short chain glycol compounds, especially in the absence of pre-masking and / or post-recovery.

[0559] Table 19. Simulated solution D (mixture of various diol compounds).

[0560] Diol Compounds Concentration (wt%) 1,3-Propanediol 0.10 1,4-Butanediol 0.10 1,5-Pentanediol 0.10 1,6-Hexanediol 0.10 1,7-Heptanediol 0.10 1,8-Octanediol 0.10 Ion exchange water -

[0561] Table 20. Some results using IEX-I's strong cationic resin, polystyrene (SK1BH) Mitsubishi DIAION.

[0562] Diol Compounds Total loss rate of each diol / wt% 1,3-Propanediol 0.105 1,4-Butanediol 1.31 1,5-Pentanediol 4.95 1,6-Hexanediol 12.5 1,7-Heptanediol 21.6 1,8-Octanediol 42.3

[0563] Table 21. Some results using the strong anionic resin of IEX-I, polystyrene (SA10AOH) Mitsubishi DIAION.

[0564]

[0565]

[0566] This example demonstrates that certain supported ion exchange resins, such as hydrophilic polymers (eg, polyacrylic acid gel), can greatly enhance the separation of diol compounds from an initial aqueous formulation.

[0567] Table 22. Some results using IEX-I's strong anionic resin, polyacrylic acid type, gel (HPR4850Cl).

[0568] Diol Compounds Total loss rate of each diol / wt% 1,3-Propanediol 0.306 1,4-Butanediol 0.693 1,5-Pentanediol 0.583 1,6-Hexanediol 0.280 1,7-Heptanediol 0.424 1,8-Octanediol 0.609

[0569] Table 23. Some results using IEX-I's strong anion resin, polyacrylic acid type, macroporous (SCAV4Cl).

[0570] Diol Compounds Total loss rate of each diol / wt% 1,3-Propanediol 0.953 1,4-Butanediol 0.664 1,5-Pentanediol 0.584 1,6-Hexanediol 0.607 1,7-Heptanediol 1.200 1,8-Octanediol 0.958

[0571] Example 3: Exemplary Ion Exchange Techniques

[0572] Among other things, the present disclosure demonstrates that the various techniques provided can be scaled up for large-scale purification and production, including various commercial scales. Certain useful techniques are described below as examples.

[0573] Resin Pretreatment. The resin can be pretreated using a variety of techniques. Some useful techniques are described below as examples. Before, during and / or after pretreatment, various parameters can be evaluated, such as the integrity of the resin and the pH of the effluent.

[0574] Ion exchange resin (H + / OH - Pretreatment of commercially available resin (free or free resin): Stir commercially available resin (400 mL) and wash with water (3 kg) for 1 hour. Soak the resin in pure water for 12 hours. Recover the soaked resin by filtration.

[0575] Ion exchange resin (Cl - Pretreatment of the resin: The resin (400 mL) was stirred and regenerated into OH in a 10% aqueous sodium hydroxide solution (2 kg). - The regenerated resin was stirred and washed with water (3 kg). The washed resin was soaked in water for 12 hours. The soaked resin was recovered by filtration.

[0576] As described herein, various techniques include pre-masking and / or post-recovery. For pre-masking, various parameters can be evaluated, such as the concentration and / or dosage of the diol compound and the masking time, to determine suitable conditions according to the present disclosure. Those skilled in the art who read the present disclosure can evaluate and determine suitable parameters for post-recovery according to the present disclosure, such as solvent systems and processing times. Some pre-masking and / or post-recovery techniques are described below as examples in one or more schemes.

[0577] Solution IEX-I

[0578] (i) The pretreated resin (400 mL) was contacted with the simulated solution (2 L) for 1 hour with stirring. The resin was removed by filtration, and the treated filtrate was analyzed (e.g., by high performance liquid chromatography (HPLC) and / or ion chromatography (IC)).

[0579] Protocol IEX-II (pre-masking and post-recovery)

[0580] (i) Pre-masking: The pretreated resin (400 mL) is contacted with a 0.5% aqueous solution of a diol compound, such as 1,6-hexanediol (HDO) (1.5 kg) with stirring for 30 minutes. The resin is recovered by filtration. The filtrate is analyzed (e.g., by high performance liquid chromatography (HPLC) and / or ion chromatography (IC)). The loss of the diol compound (e.g., HDO) during the pre-masking period is evaluated.

[0581] (ii) The resin is contacted with the simulated solution (2 L) with stirring for 1 hour. The resin is then recovered by filtration, and the filtrate is analyzed (e.g., by high performance liquid chromatography (HPLC) and / or ion chromatography (IC)). The loss of the diol compound (e.g., HDO) is evaluated.

[0582] (iii) Post-recovery: The recovered resin was stirred with water (2 L) for 1 hour. The resin was then recovered by filtration, and the filtrate was analyzed (e.g., by high performance liquid chromatography (HPLC) and / or ion chromatography (IC)). The amount of diol compound (e.g., HDO) recovered was evaluated.

[0583] Protocol IEX-III (pre-masking)

[0584] (i) Pre-masking: The pretreated resin (400 mL) is contacted with a 0.5% aqueous solution of a diol compound, such as 1,6-hexanediol (HDO) (1.5 kg) with stirring for 30 minutes. The resin is recovered by filtration. The filtrate is analyzed (e.g., by high performance liquid chromatography (HPLC) and / or ion chromatography (IC)). The loss of the diol compound (e.g., HDO) during the pre-masking period is evaluated.

[0585] (ii) The resin is contacted with the simulated solution (2 L) with stirring for 1 hour. The resin is then recovered by filtration, and the filtrate is analyzed (e.g., by high performance liquid chromatography (HPLC) and / or ion chromatography (IC)). The loss of the diol compound (e.g., HDO) is evaluated.

[0586] Protocol IEX-IV (post-recovery)

[0587] (i) The pretreated resin (400 mL) was contacted with the simulated solution (2 L) with stirring for 1 hour. The resin was then recovered by filtration, and the filtrate was analyzed (e.g., by high performance liquid chromatography (HPLC) and / or ion chromatography (IC)). The loss of the diol compound (e.g., HDO) was evaluated.

[0588] (ii) Post-recovery: The recovered resin was stirred with water (2 L) for 1 hour. The resin was then recovered by filtration, and the filtrate was analyzed (e.g., by high performance liquid chromatography (HPLC) and / or ion chromatography (IC)). The amount of diol compound (e.g., HDO) recovered was evaluated.

[0589] Some large-scale experimental results obtained using simulated solution A and schemes I-IV are listed below. As shown herein, in various embodiments, the technology provided by the present disclosure can effectively remove anions and / or cations, and reduce the loss of diol compounds. In some embodiments, for resins with hydrophobic base polymers (e.g., polystyrene), pre-masking and / or post-recovery can significantly reduce the loss of diol compounds. In some embodiments, the technology provided includes the use of resins with hydrophilic base polymers. In some embodiments, the technology provided includes the use of resins with polyacrylic acid polymers. In some embodiments, as shown herein, polyacrylic acid polymers can achieve effective ion exchange and maintain the loss of diol compounds at a lower level.

[0590] Table 25. Some results for strong cation exchange resin, polystyrene (SK1BH) Mitsubishi DIAION.

[0591] Total HDO loss rate / wt% <![CDATA[K + / ppm]]> <![CDATA[Mg 2+ / ppm]]> Simulated solution - 3100 91 IEX-I 10.3 120 0.4 IEX-II 0.431 123 0.7 IEX-III 8.13 131 1.0 IEX-IV 1.01 130 0.4

[0592] Table 26. Some results for strong anion exchange resin, polystyrene (SA10AOH) Mitsubishi DIAION.

[0593]

[0594]

[0595] Table 27. Certain results for strong anion exchange resin, polyacrylic acid type (HPR4850Cl) AmberLite DuPont.

[0596] Total HDO loss rate / wt% Pyruvic acid / ppm <![CDATA[SO4 2- / ppm]]> <![CDATA[PO4 3- / ppm]]> Simulated solution A - 3200 350 2400 IEX-I 0.680 90 4.3 1.6 IEX-II 0.329 86 4.4 1.1 IEX-III 0.673 97 4.1 1.2 IEX-IV 0.331 98 4.0 1.5

[0597] Table 28. Certain results for strong anion exchange resin, polyacrylic acid type (SCAV4Cl) AmberLite DuPont.

[0598] Total HDO loss rate / wt% Pyruvic acid / ppm <![CDATA[SO4 2- / ppm]]> <![CDATA[PO4 3- / ppm]]> Simulated solution A - 3200 350 2400 IEX-I 0.659 175 6.4 3.5 IEX-II 0.281 173 6.2 3.0 IEX-III 0.624 174 6.9 3.4 IEX-IV 0.243 170 6.1 3.1

[0599] As described herein, various solvent systems, such as those that are alcohols or contain alcohols (such as ethanol), can be used for post-recovery washing. Certain results are shown below to demonstrate their effectiveness. The ion exchange (IEX) resin has been pretreated.

[0600] Protocol IEX-V (pre-masking and post-recovery (using ethanol))

[0601] (i) Pre-masking: The pretreated resin (400 mL) was contacted with a 0.5% aqueous solution of the diol compound (1.5 kg) under stirring for 30 minutes. The resin was recovered by filtration. The filtrate was analyzed (e.g., by high performance liquid chromatography (HPLC) and / or ion chromatography (IC)). The loss of the diol compound (e.g., HDO) during the pre-masking period was evaluated.

[0602] (ii) The resin is contacted with the simulated solution (2 L) with stirring for 1 hour. The resin is then recovered by filtration, and the filtrate is analyzed (e.g., by high performance liquid chromatography (HPLC) and / or ion chromatography (IC)). The loss of the diol compound (e.g., HDO) is evaluated.

[0603] (iii) Post-recovery: The recovered resin was stirred with ethanol (2 L) for 1 hour. The resin was then recovered by filtration, and the filtrate was analyzed (e.g., by high performance liquid chromatography (HPLC) and / or ion chromatography (IC)). The amount of diol compound (e.g., HDO) recovered was evaluated.

[0604] IEX-VI (post-recovery (using ethanol))

[0605] (i) The pretreated resin (400 mL) was contacted with the simulated solution (2 L) with stirring for 1 hour. The resin was then recovered by filtration, and the filtrate was analyzed (e.g., by high performance liquid chromatography (HPLC) and / or ion chromatography (IC)). The loss of the diol compound (e.g., HDO) was evaluated.

[0606] (ii) Post-recovery: The recovered resin was stirred with ethanol (2 L) for 1 hour. The resin was then recovered by filtration, and the filtrate was analyzed (e.g., by high performance liquid chromatography (HPLC) and / or ion chromatography (IC)). The amount of diol compound (e.g., HDO) recovered was evaluated.

[0607] As shown herein, ethanol can effectively reduce the loss of diol compounds.

[0608] Table 29. Some results for strong cation exchange resin, polystyrene (SK1BH) Mitsubishi DIAION.

[0609]

[0610] Example 4. The provided technology can be used in various application settings

[0611] Among other things, the provided techniques can be used in a variety of settings and instruments. For example, in some embodiments, the provided techniques can be used in the column settings described in this example.

[0612] The ion exchange (IEX) resin is pretreated. For example, in some embodiments, for H + / OH - For example, about 300 mL of the resin is stirred and washed with an appropriate amount of pure water (about 2250 g) for a suitable period of time (e.g., about 1 hour). The washed resin is soaked in pure water for another period of time, such as about 12 hours. Thereafter, the soaked resin is recovered by filtration. In some embodiments, for Cl - The resin is stirred with about 300 mL of the resin and regenerated into OH using an appropriate amount of an alkali solution of appropriate concentration (e.g., about 10% sodium hydroxide aqueous solution, about 1500 g). - The regenerated resin is stirred and washed with an appropriate amount of ion exchange water (e.g., about 2250 g). The washed resin is soaked in pure water for an appropriate period of time, e.g., about 12 hours. The soaked resin is recovered by filtration.

[0613] Some useful scenarios are described below as examples.

[0614] Protocol IEX-I (a "conventional" method that can be used as a reference method for comparison)

[0615] (i) 300 mL of the pretreated resin was filled into a column, and pure water was allowed to flow at 20 mL / min at 25° C. for 10 minutes.

[0616] (ii) 12350 mL of the simulated solution A was allowed to flow at a flow rate of 20 mL / min at 25°C, and each portion of the effluent was collected.

[0617] (iii) The collected effluent from each fraction was analyzed by high performance liquid chromatography (HPLC) and ion chromatography (IC) to assess the breakthrough point and loss of HDO.

[0618] Scheme IEX-II (pre-masking + post-recovery)

[0619] (i) 300 mL of the pretreated resin was filled into a column, and pure water was allowed to flow at a flow rate of 20 mL / min at 25° C. for 10 minutes.

[0620] (ii) A 0.5% HDO aqueous solution was allowed to flow at a flow rate of 20 mL / min at 25°C for 30 minutes (pre-masking), and each fraction of the effluent was collected.

[0621] (iii) 13 L of the simulated solution A was allowed to flow at a flow rate of 20 mL / min at 25°C, and each portion of the effluent was collected.

[0622] (iv) 2700 mL of pure water was allowed to flow at a flow rate of 20 mL / min at 25°C, and each portion of the effluent was collected (for later recovery).

[0623] (v) Analyze each fraction of the collected effluent by high performance liquid chromatography (HPLC) and ion chromatography (IC) to estimate the breakthrough point and loss of HDO.

[0624] Protocol IEX-III (pre-masking only)

[0625] (i) 300 mL of the pretreated resin was filled into a column, and pure water was allowed to flow at a flow rate of 20 mL / min at 25° C. for 10 minutes.

[0626] (ii) A 0.5% HDO aqueous solution was allowed to flow at a flow rate of 20 mL / min at 25°C for 30 minutes (pre-masking), and each fraction of the effluent was collected.

[0627] (iii) 13 L of the simulated solution A was allowed to flow at a flow rate of 20 mL / min at 25°C, and each portion of the effluent was collected.

[0628] (iv) Analyze each fraction of the collected effluent by high performance liquid chromatography (HPLC) and ion chromatography (IC) to estimate the breakthrough point and loss of HDO.

[0629] Protocol IEX-IV (Post-recovery Method)

[0630] (i) 300 mL of the pretreated resin was filled into a column, and pure water was allowed to flow at a flow rate of 20 mL / min at 25° C. for 10 minutes.

[0631] (ii) 13 L of the simulated solution A was allowed to flow at a flow rate of 20 mL / min at 25°C, and each portion of the effluent was collected.

[0632] (iii) 2700 mL of pure water was allowed to flow at a flow rate of 20 mL / min at 25°C, and each portion of the effluent was collected (for later recovery).

[0633] (iv) Analyze each fraction of the collected effluent by high performance liquid chromatography (HPLC) and ion chromatography (IC) to estimate the breakthrough point and loss of HDO.

[0634] In some embodiments, high performance liquid chromatography (HPLC) is used to quantify the amount of HDO, and ion chromatography (IC) is used to quantify the ion concentration. In some embodiments, the total HDO loss rate is calculated as follows (can also be used for other diol compounds):

[0635]

[0636] The total HDO loss during the ion exchange process = the HDO loss caused by ion exchange before reaching the breakthrough point + the HDO loss caused by pre-masking (if pre-masking is performed) - the HDO amount recovered by post-recovery (if post-masking is performed).

[0637] As shown below, the provided techniques, such as resins with hydrophilic base polymers, pre-masking and / or post-recovery, can effectively reduce the loss of diol compounds.

[0638] Table 30. Some results for strong cation exchange resin, polystyrene (SK1BH) Mitsubishi DIAION.

[0639] Total HDO loss rate / wt% <![CDATA[K + / ppm]]> <![CDATA[Mg 2+ / ppm]]> Simulated solution A - 3100 91 IEX-I 2.39 2.7 0.3 IEX-II 1.13 2.7 0.2 IEX-III 1.82 2.8 0.1 IEX-IV 1.43 2.3 0.2

[0640] Table 31. Some results for strong anion exchange resin, polystyrene (SA10AOH) Mitsubishi DIAION.

[0641]

[0642]

[0643] Table 32. Certain results for strong anion exchange resin, polyacrylic acid type (HPR4850Cl) AmberLite DuPont.

[0644]

[0645] Table 33. Certain results for strong anion exchange resin, polyacrylic acid type (SCAV4Cl) AmberLite DuPont.

[0646]

[0647] Example 5: Evaporation and distillation

[0648] There are a variety of evaporation and / or distillation techniques and can be utilized in accordance with the present disclosure. In some embodiments, the diol compound is produced during fermentation and subsequently purified by filtration followed by ion exchange. The ion-exchanged solution is evaporated, for example, in a multiple-effect evaporation process under vacuum to a final concentration of about 30-95% (e.g., about 40-95%, 40-90%, 50%-90%, or 80%-95%; or about 30%, 40%, 50%, 60%, 70%, 80%, or 90%) wt%. In some embodiments, evaporation increases the concentration. In some embodiments, evaporation removes water. In some embodiments, evaporation reduces the steam load in the distillation column. In some embodiments, evaporation facilitates distillation to meet the final specifications of the product (in some embodiments, depending on the application, for example, in some embodiments, as a raw material for polyurethane, one or more or all of purity ≥99.5% (wt%), APAH ≤10, water ≤0.1% (wt%), CPR value ≤1, acid value ≤0.1, ester value ≤0.5). In some embodiments, evaporation removes low-boiling organic compounds together with water while minimizing diol loss, for example, by controlling pressure, temperature, time, etc.

[0649] In some embodiments, a rising film evaporator is used. For example, in some embodiments, a series of rising film evaporators are used to evaporate the aqueous mixture. In some embodiments, the outlet of an ion exchange column (e.g., an anion exchange column) is fed to a first effect evaporator by a feed pump and then passed through a series of evaporators (n=1, 2, 3...) until the desired concentration level is reached, after which distillation can be used for further purification.

[0650] Various distillation techniques can be utilized according to the present disclosure. In some embodiments, a crude diol compound mixture is further purified from about 80%-95% wt% using a continuous distillation apparatus to, for example, about 95%, 96%, 97%, 98%, 99%, or >99% wt% purity. In some embodiments, the crude diol compound composition is fractionated in a continuous countercurrent multi-stage fractionator under high vacuum to provide the desired diol compound product (e.g., 1,6-HDO).

[0651] Example 6: Preparation of high purity compounds

[0652] Certain useful techniques for preparing high-purity compounds (e.g., 1,6-HDO) and certain high-purity preparations (e.g., high-purity preparations of 1,6-HDO) are shown as examples herein. In some embodiments, a method for obtaining a compound (e.g., 1,6-hexanediol) includes culturing a microorganism in a culture medium containing a raw material derived from a biomass resource, and then preparing high-purity 1,6-hexanediol by further purification. It should be understood by those skilled in the art that the techniques described in this example can be combined with other techniques (e.g., pretreatment and / or post-treatment) described herein to provide high-purity and / or high-yield compounds.

[0653] In some embodiments, provided techniques include:

[0654] Step (a): Filtration and first ion exchange. For example, in some embodiments, the 1,6-HDO preparation is filtered to remove microorganisms and other insolubles. The filtered 1,6-HDO preparation is then contacted with a cation exchange resin (DIAION SK1BH) at 40° C. in a batch manner. After contacting for 3 hours, the resin is removed by filtration to provide a 1,6-HDO composition A;

[0655] Step (b): Second exchange. In some embodiments, the 1,6-HDO composition A is contacted with an anion exchange resin (DIAION SA10AOH) at 40° C. in a batch mode. After contacting for 3 hours, the resin is removed by filtration to provide a 1,6-HDO composition B;

[0656] Step (c): distillation to remove water (and / or low boiling impurities). In some embodiments, water is removed from 1,6-HDO composition B by heating at 70° C. under continuous feed operation conditions by a thin film distillation apparatus. 1,6-HDO composition B is continuously treated until the water content is ≤200 ppm, thereby providing 1,6-HDO composition C;

[0657] Step (d): distillation to remove impurities with relatively high boiling points (e.g., higher than water). In some embodiments, the boiling point of such impurities is lower than the boiling point of the desired compound (e.g., 1,6-HDO). For example, in some embodiments, 1,6-HDO composition C is continuously supplied to a distillation apparatus equipped with an Oldershaw column, the column top is maintained at 240° C., and volatile contaminants are removed to provide 1,6-HDO composition D; and / or

[0658] Step (e): Distillation to provide a high-purity compound. In some embodiments, the desired compound (e.g., 1,6-HDO) is distilled to provide a high-purity preparation. For example, in some embodiments, the 1,6-HDO composition D is continuously supplied to a distillation apparatus equipped with an Oldershaw column, the column bottom is maintained at 260° C., and the purified 1,6-HDO is evaporated, and its purity is determined by high performance liquid chromatography (HPLC) and gas chromatography (GC) to be >95% w / w.

[0659] In some embodiments, a method for preparing a diol compound (e.g., 1,6-hexanediol) includes culturing a microorganism in a culture medium containing a feedstock derived from a biomass resource to produce the compound, and purifying the compound (e.g., 1,6-hexanediol) by techniques described herein (e.g., filtration, one or more ion exchanges, one or more distillations (which remove impurities and / or enrich the compound), etc.).

[0660] In some embodiments, a composition comprising, for example, 1,6-hexanediol is provided by culturing a microorganism. In some embodiments, the composition comprises a compound in a culture medium and a microorganism. In some embodiments, the microorganism is removed from the culture medium as needed, for example, by filtration and / or centrifugation. It will be appreciated by those skilled in the art that various techniques can be used to remove the microorganism. In some embodiments, microorganisms and / or solid matter are removed by membrane separation and / or centrifugation. In some embodiments, continuous centrifuges can be used for continuous centrifugation. Examples of continuous centrifuges include cage centrifuges, disc centrifuges, nozzle centrifuges, or other similar centrifugation techniques. In some embodiments, a centrifugation technique is used alone; in some embodiments, two or more centrifugation techniques are used in combination.

[0661] In some embodiments, separation is performed using a membrane, for example, a membrane having a pore size of 10.0 μm or less can be used alone, or two or more membranes of different or identical pore sizes can be used in combination. In some embodiments, the membrane can be one of a variety of shapes, for example, a flat membrane, a hollow fiber membrane, a spiral membrane, a tubular membrane, or a pleated membrane. In some embodiments, a plurality of membranes can be used in the filtration, and these membranes can include more than one shape. According to the present disclosure, various types of filtration can be used, for example, dead end filtration, tangential flow filtration, etc.

[0662] In some embodiments, purification of a diol formulation (e.g., aqueous 1,6-HDO) includes ion exchange. In some embodiments, ion exchange is performed in series, wherein cation exchange and anion exchange are performed sequentially. In some embodiments, cation exchange is performed first, followed by anion exchange. In some embodiments, anion exchange is performed first, followed by cation exchange. In some embodiments, pressure is applied to the liquid in contact with the ion exchange resin. In some embodiments, only gravity pressure is applied to the aqueous diol formulation in contact with the ion exchange resin.

[0663] In some embodiments, purification includes distillation. In some embodiments, distillation is used to remove water, remove components with a boiling point lower than the compound (e.g., 1,6-hexanediol), and / or remove components with a boiling point higher than the compound (e.g., 1,6-hexanediol). In some embodiments, water is removed, components with a boiling point lower than the diol compound (e.g., 1,6-hexanediol), and components with a boiling point higher than the diol compound (e.g., 1,6-hexanediol) are removed in the following order.

[0664] In some embodiments, the ion exchange step comprises the following steps (a) and / or (b), and in some cases, in that order.

[0665] Step (a): contacting a diol compound composition (eg, a 1,6-hexanediol composition, for example, after membrane separation or / and centrifugation) with a cation exchange resin to obtain a diol compound composition A; and

[0666] Step (b): The diol compound composition A obtained in step (a) is contacted with an anion exchange resin to provide a diol compound composition B.

[0667] In some embodiments, examples of components removed by contacting with a cation exchange resin in step (a) include metal cations and ammonium ions.

[0668] According to the present disclosure, many kinds of cation exchange resins can be used. Examples of cation exchange resins include strongly acidic and weakly acidic resins. In some embodiments, the cation exchange resin is or comprises styrene, acrylic acid or hydrogel resins, or any combination thereof. In some embodiments, the cation exchange resin is or comprises a gel-type, porous or high-porous system. The cation exchange resin can be in different physical forms, for example, powdered, spherical, fibrous, membranous, etc.

[0669] In some embodiments, examples of components removed by contacting with an anion exchange resin, for example in step (b), include inorganic ions (eg, chloride ions, sulfate ions, phosphate ions, etc.) and / or organic acid ions, and the like.

[0670] According to the present disclosure, many kinds of anion exchange resins can be used. Examples of anion exchange resins include strong basic and weak basic resins. In some embodiments, the anion exchange resin is or comprises styrene, acrylic acid or hydrogel resins, or any combination thereof. In some embodiments, the anion exchange resin is or comprises a gel-type, porous or high-porous system. The anion exchange resin can be in different physical forms, for example, powdered, spherical, fibrous, film-like, etc.

[0671] In accordance with the present disclosure, various techniques can be used to contact the composition with the ion exchange resin, including batch processes, column processes, and the like.

[0672] In some embodiments, cation exchange is performed before anion exchange. In some embodiments, anion exchange is performed before cation exchange. In some embodiments, the composition containing the diol compound (e.g., 1,6-HDO) obtained by centrifugation and / or membrane separation may be contacted with an anion exchange resin first and then with a cation exchange resin. In some embodiments, step (a) and step (b) may be performed simultaneously. In some embodiments, the diol compound composition (e.g., 1,6-HDO) obtained by membrane separation and / or centrifugation may be contacted with a cation exchange resin and an anion exchange resin at the same time.

[0673] Distillation process

[0674] In some embodiments, distillation is performed through steps (c), (d) and (e), optionally in this order, to obtain, for example, composition E of 1,6-HDO. In some embodiments, purification optionally includes step (f):

[0675] Step (c): distillation to remove water from a composition containing a diol compound (e.g., 1,6-hexanediol). In some embodiments, the composition obtained after ion exchange (e.g., diol compound composition B) is distilled to provide a diol compound composition C (remaining composition);

[0676] Step (d): distillation to remove components with a boiling point lower than the target diol compound (e.g., 1,6-hexanediol). In some embodiments, the composition obtained after step (c) (e.g., diol compound composition C) is distilled to provide diol compound composition D (remaining composition);

[0677] Step (e): distillation to remove components having a boiling point higher than the target diol compound (e.g., 1,6-hexanediol). In some embodiments, the composition obtained after step (d) (e.g., diol compound composition D) is distilled to provide diol compound composition E (components collected from the distillation); and

[0678] Step (f): distilling the composition obtained in step (e) (diol compound composition E) to obtain a diol compound (eg, 1,6-hexanediol) of higher purity.

[0679] In some embodiments, the component having a lower boiling point than the target diol, such as in the case of 1,6-hexanediol, is, for example, 1,3-propylene glycol.

[0680] In some embodiments, the component with a higher boiling point than the target diol, such as in the case of 1,6-hexanediol, is, for example, glycerol.

[0681] In accordance with the present disclosure, various distillation techniques can be used. In some embodiments, the distillation method is continuous distillation. In some embodiments, the distillation method is batch distillation.

[0682] Step (c)

[0683] In some embodiments, the method includes step (c), i.e., removing water. In some embodiments, water is removed from the diol compound composition (e.g., diol compound composition B) by heating the diol compound composition obtained, for example, in the ion exchange step to a temperature at which water evaporates. In some embodiments, the pressure is reduced.

[0684] According to the present disclosure, various techniques can be used to carry out step (c). Examples of useful apparatus include continuous distillation columns, multi-purpose tanks, thin film evaporators, evaporators, batch stills, atomizing separators, and the like.

[0685] Step (d)

[0686] In some embodiments, the method includes step (d), i.e., removing components having a boiling point lower than the desired diol compound (e.g., 1,6-hexanediol). For example, in some embodiments, such components are removed from a diol compound composition (e.g., diol compound composition C (e.g., wherein the diol compound is 1,6-HDO)).

[0687] In some embodiments, step (d) removes low boiling components. In some embodiments, step (d) removes trace amounts of components that cause coloration. For example, in some embodiments, for the purification of 1,6-HDO, components with a boiling point lower than 1,6-hexanediol are removed or reduced, including certain components that cause coloration, certain hydrogenation products of components that cause coloration.

[0688] According to the present disclosure, various techniques can be used to carry out step (d). For example, according to the present disclosure, the distillation in step (d) can be carried out using means and apparatus such as atmospheric distillation, vacuum distillation, and pressure distillation. Useful apparatuses include continuous distillation towers, multi-purpose tanks, thin film evaporators, evaporators, batch distiller, atomizing separators, and the like. Those skilled in the art can evaluate and set the operating conditions used in step (d) by considering factors such as the diol compound composition C (e.g., wherein the diol compound is 1,6-HDO), the purity to be obtained, and the like.

[0689] Step (e)

[0690] In some embodiments, the method includes step (e), i.e., removing components having a boiling point higher than the desired diol compound (e.g., 1,6-hexanediol). For example, in some embodiments, such components are removed from a diol compound composition (e.g., diol compound composition D (e.g., wherein the diol compound is 1,6-HDO)).

[0691] In some embodiments, the component with a boiling point higher than the target diol (e.g., 1,6-hexanediol) is specific to the fermentation process. In some embodiments, it is a nitrogen-containing component derived from amino acids or proteins. In some embodiments, it is a sugar or a decomposition product thereof.

[0692] According to the present disclosure, various techniques can be used to carry out step (e). Useful devices include continuous distillation columns, multi-purpose tanks, thin film evaporators, evaporators, batch distiller, atomizing separators, etc. Those skilled in the art can evaluate and set the operating conditions used in step (e) by considering factors such as the diol compound composition D (for example, wherein the diol compound is 1,6-HDO), the purity to be obtained, and the like.

[0693] Step (f)

[0694] In some embodiments, the diol compound composition E obtained, for example, through steps (c), (d), and (e) is further purified to obtain a composition with higher purity.

[0695] According to the present disclosure, various techniques can be used to carry out step (f). Useful devices include continuous distillation towers, multi-effect tanks, thin film evaporators, evaporators, batch distiller, atomizing separators, etc. Those skilled in the art can consider the composition of the diol compound to be purified, the purity to be finally obtained, and other factors to evaluate and set the operating conditions used in step (f).

[0696] In some embodiments, a diol compound composition (eg, a 1,6-HDO composition) is obtained by performing step (e) and step (f) as necessary.

[0697] In some embodiments, steps (c), (d) and (e) may be performed in this order. In some embodiments, steps (c), (d) and (e) may be performed in a different order than described above.

[0698] Figure 1 A useful process is described as an example in . In some embodiments, such a process is used to purify 1,6-HDO. In some embodiments, the filtration is microfiltration.

[0699] Step (a): Ion exchange to remove cations

[0700] In some embodiments, cations are removed from a diol compound composition (e.g., a diol compound composition after microorganisms have been removed, such as a 1,6-hexanediol composition). In some embodiments, cations are removed by membrane separation. In some embodiments, step (a) removes or reduces the content of various cations. In some embodiments, cation exchange is performed in batches. In some embodiments, the contact temperature with the cation exchange resin is about 40°C, and DIAION SK1BH manufactured by Mitsubishi Chemical Co., Ltd. is added to the diol compound composition (e.g., 1,6-hexanediol composition) and stirred for 3 hours. After stirring, filtration is performed to obtain a diol compound composition (e.g., diol compound composition A (e.g., 1,6-HDO composition A) as a filtrate).

[0701] Step (b): Ion exchange to remove anions

[0702] In some embodiments, anions in a diol compound (e.g., 1,6-HDO) composition (e.g., diol compound composition A) are removed. In some embodiments, step (b) removes or reduces the content of various anions. In some embodiments, anion exchange is performed in a batch manner. In some embodiments, the contact temperature with the anion exchange resin is about 40°C, and DIAION SA 10AOH produced by Mitsubishi Chemical Co., Ltd. is added to the diol compound composition (e.g., 1,6-hexanediol composition) and stirred for 3 hours. After stirring, filtration is performed to obtain a diol compound composition (e.g., diol compound composition B (e.g., 1,6-HDO composition B) as a filtrate).

[0703] Step (c): removing water.

[0704] In some embodiments, the step is to remove water. In some embodiments, step (c) includes removing water. In some embodiments, water is removed in the evaporation step. In some embodiments, a thin film distiller is used as the apparatus for step (c). In some embodiments, the jacket temperature is set to about 70°C, and a composition comprising a diol compound (e.g., 1,6-hexanediol) is continuously introduced to evaporate water (and other components of the composition that may evaporate). In some embodiments, while evaporating water, the dehydrated diol compound composition (e.g., 1,6-HDO composition C) is continuously removed from the bottom of the apparatus. In some embodiments, the water concentration in diol compound composition C (e.g., 1,6-HDO composition C) is 0.020 mass % (200 mass ppm). Step (d): Distillation separation of low-boiling components

[0705] In some embodiments, components having a boiling point lower than that of the target diol compound (e.g., 1,6-hexanediol) in the diol compound composition (e.g., diol compound composition C (e.g., 1,6-HDO composition C)) are removed by a continuous distillation tower. In some embodiments, an Oldershaw distillation tower is used as a distillation tower in step (d). In some embodiments, the diol compound composition (e.g., 1,6-HDO composition C) obtained in step (c) is continuously supplied to the distillation tower, and the tower top temperature is controlled at a constant temperature of about 240° C. In some embodiments, low-boiling point components are removed, and a diol compound composition having a lower content of low-boiling point components is obtained from the bottom of the distillation tower, thereby obtaining a diol compound composition D (e.g., 1,6-HDO composition D).

[0706] Step (e): Separation of high boiling point components by distillation

[0707] In some embodiments, components having a boiling point higher than that of the target diol compound (e.g., 1,6-hexanediol) are removed by distillation. In some embodiments, a continuous distillation tower is used for distillation. In some embodiments, an Oldershaw distillation tower is used as the distillation tower of step (e). In some embodiments, the diol compound composition (e.g., 1,6-HDO composition D) obtained in step (d) is continuously supplied to the distillation tower, and the tower bottom temperature is controlled at a constant temperature of about 260°C. In some embodiments, high-boiling-point components in the diol compound composition (e.g., 1,6-HDO composition D) are removed by continuous extraction from the bottom of the tower. In some embodiments, a diol compound composition (e.g., 1,6-HDO composition E) is obtained as a tower top distillate. In some embodiments, a diol compound composition (e.g., 1,6-HDO composition E as a tower top distillate) is obtained by removing components having a boiling point higher than that of the target diol compound (e.g., 1,6-hexanediol) from the top of the tower.

[0708] In some embodiments, the purity of the obtained diol compound (eg, 1,6-hexanediol) is determined by high performance liquid chromatography (HPLC) and / or gas chromatography (GC). In some embodiments, the purity is confirmed to be 95% or higher, respectively.

[0709] Equivalent solution

[0710] Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, that many equivalents exist to the specific embodiments of the invention described herein.

Claims

1. A method for purifying an aqueous initial preparation containing a diol compound, the method comprising contacting the aqueous initial preparation with an ion exchange resin, wherein the base polymer of the resin is a hydrophilic polymer, wherein: The diol compound is 1,6-hexanediol; as well as Prior to contacting the aqueous initial formulation with the ion exchange resin, the ion exchange resin is pre-masked by contacting the ion exchange resin with a pre-masking formulation comprising the diol compound.

2. A method for purifying an aqueous initial preparation comprising a diol compound, wherein the diol compound contains 5 to 12 carbon atoms, and wherein the aqueous initial formulation contains greater than 50% water; the method comprising: contacting the aqueous initial formulation with an ion exchange resin, wherein the resin is a hydrophilic resin; or A method of purifying an aqueous initial formulation comprising a diol compound comprises contacting the aqueous initial formulation with an ion exchange resin, wherein the base polymer of the resin is a hydrophilic polymer.

3. The method according to any one of the preceding claims, wherein the hydrophilic resin is a polyacrylic acid resin.

4. The method according to claim 3, wherein the polyacrylic acid resin is a strong anion exchange resin, a weak anion exchange resin or a weak cation exchange resin. The method according to claim 3 , wherein the hydrophilic resin is a polymethacrylic acid resin.

6. The method of claim 2, further comprising contacting the ion exchange resin with a pre-masking formulation comprising the diol compound prior to contacting the aqueous initial formulation with the ion exchange resin.

7. A method for purifying an aqueous initial formulation comprising a diol compound, comprising contacting an ion exchange resin with a pre-masked formulation comprising the diol compound, and contacting the aqueous initial formulation with the pre-masked ion exchange resin; or a method for purifying an aqueous initial formulation comprising a diol compound, comprising contacting an ion exchange resin with a pre-masked formulation comprising the diol compound, and contacting the aqueous initial formulation with a pre-masked ion exchange resin; optionally further comprising contacting the ion exchange resin with a post-recovery solvent system after contacting the resin with the aqueous initial formulation; or A method of purifying an aqueous initial preparation containing a diol compound, comprising contacting the aqueous initial preparation with an ion exchange resin, and after contacting the aqueous initial preparation with the ion exchange resin, contacting the ion exchange resin with a post-recovery solvent system; or A method of purifying an aqueous initial preparation comprising a diol compound comprises contacting an ion exchange resin with a pre-masked preparation comprising the diol compound, contacting the aqueous initial preparation with the pre-masked ion exchange resin, and contacting the ion exchange resin with a post-recovery solvent system after contacting the aqueous initial preparation with the pre-masked ion exchange resin.

8. The method of any of the preceding claims, wherein the aqueous initial formulation comprises greater than about 50% water, or wherein the content of water in the formulation is in the range of 51% to 99%, or wherein the aqueous initial formulation comprises greater than about 70% water, or wherein the aqueous initial formulation comprises greater than about 90% water.

9. The method of any one of the preceding claims, wherein the aqueous initial formulation independently comprises about or at least about 50, 60, 70, 80, 90, 100, 150, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1500, 2000, 3000, 4000, 5000, 6000, 7000, 8000, or 10000 ppm (w / w) of one or more ions and / or impurities, and / or wherein the aqueous initial formulation comprises about or at least about 3000 ppm (w / w) of K + , and / or or wherein the aqueous initial formulation comprises about or at least about 90 ppm (w / w) Mg 2+ , and / or wherein the aqueous initial formulation comprises about or at least about 3000 ppm (w / w) of pyruvic acid, and / or wherein the aqueous initial formulation comprises about or at least about 350 ppm (w / w) of SO 2- , and / or wherein the aqueous initial formulation comprises about or at least about 2000 ppm (w / w) of phosphate (H2PO4 - 、HPO4 2- and / or PO4 3- ).

10. The method according to any one of the preceding claims, comprising contacting the aqueous initial formulation with an acidic resin, and / or comprising contacting the aqueous initial formulation with a strongly acidic resin, and / or comprising contacting the aqueous initial formulation with a weakly acidic resin.

11. The method of any one of claims 7 to 10, wherein the base polymer of the resin is hydrophobic, or wherein the resin is a polystyrene resin.

12. The method according to any one of claims 7 to 10, wherein the base polymer of the resin is hydrophilic, or wherein the resin is a polyacrylic resin, or wherein the resin is a polymethacrylic resin.

13. The method according to any one of claims 1 to 10, comprising contacting the aqueous initial formulation with SK1BH resin, and / or comprising contacting the aqueous initial formulation with WK60L resin, and / or comprising contacting the aqueous initial formulation with WK10 resin.

14. The method according to any one of claims 7 to 13, wherein the resin is pretreated.

15. A method according to any one of claims 7 to 14 comprising contacting the ion exchange resin with a pre-masking formulation comprising the diol compound prior to contacting the ion exchange resin with an aqueous initial formulation.

16. The method of any one of claims 7 to 14, comprising contacting the ion exchange resin with a post-recovery solvent system after contacting the ion exchange resin with the aqueous initial formulation.

17. A method according to any one of the preceding claims, comprising contacting the aqueous initial formulation with a basic resin, and / or comprising contacting the aqueous initial formulation with a strongly basic resin, and / or comprising contacting the aqueous initial formulation with a weakly basic resin; optionally wherein the base polymer of the resin is hydrophobic or is a polystyrene resin, or optionally wherein the base polymer of the resin is hydrophilic or is a polyacrylic resin or a polymethacrylic resin.

18. The method according to any one of claims 1 to 17, comprising contacting the aqueous initial formulation with SCA10AOH resin, and / or comprising contacting the aqueous initial formulation with WA21J resin, and / or comprising contacting the aqueous initial formulation with HPR4580 Cl resin, and / or comprising contacting the aqueous initial formulation with SCAV4Cl resin, and / or comprising contacting the aqueous initial formulation with IRA67 resin.

19. The method of any one of claims 17-18, wherein the resin is pretreated.

20. The method of any one of claims 17 to 19, comprising contacting the ion exchange resin with a pre-masking formulation comprising the diol compound prior to contacting the ion exchange resin with an aqueous initial formulation.

21. The method of any one of claims 17-20, comprising contacting the ion exchange resin with a post-recovery solvent system after contacting the ion exchange resin with the aqueous initial formulation.

22. The method of any of the preceding claims, wherein the resin is characterized by an average degree of crosslinking in the range of 1% to 25%, and / or wherein the resin is characterized by an average functional group density in the range of 0.1 to 4.0 (eq / L), and / or wherein the resin is characterized by an average particle size in the range of 100 μm to 1500 μm, and / or wherein the resin is characterized as being Type 1 or Type 2.

23. The method of any of the preceding claims, wherein the concentration of the diol compound in the pre-masking formulation is about or no more than about 50% (wt %) of the diol compound, or wherein the concentration of the diol compound in the pre-masking formulation is about or no more than about 30% (wt %) of the diol compound, or wherein the concentration of the diol compound in the pre-masking formulation is about or no more than about 20% (wt %) of the diol compound, or wherein the concentration of the diol compound in the pre-masking formulation is about or no more than about 10% (wt %) of the diol compound, or wherein the concentration of the diol compound in the pre-masking formulation is about or no more than about 5% (wt %) of the diol compound, or wherein the concentration of the diol compound in the pre-masking formulation is about or no more than about 2% (wt %) of the diol compound. %), or wherein the concentration of the diol compound in the pre-masking formulation is about or not more than about 0.1% to 2% (wt %) of the diol compound, or wherein the concentration of the diol compound in the pre-masking formulation is about or not more than about 1% (wt %) of the diol compound, or wherein the concentration of the diol compound in the pre-masking formulation is about or not more than about 0.3% to 0.7% (wt %) of the diol compound, or wherein the concentration of the diol compound in the pre-masking formulation is about or not more than about 0.5% (wt %) of the diol compound, or wherein the concentration of the diol compound in the pre-masking formulation is about or not more than about 0.2% (wt %) of the diol compound, or wherein the concentration of the diol compound in the pre-masking formulation is about or not more than about 0.1% (wt %) of the diol compound.

24. The method of any of the preceding claims, wherein for each contacting of the ion exchange resin with the pre-masking formulation, about or at least about 1-1000 mg, such as about 1-500, 1-200, 1-100, 1-50, 1-20, 1-10, or about 1, 2, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 150, 200, 300, 400, 500, 600, 700, 800, 900 or 1000 mg of the diol compound is used per ml of resin.

25. A method according to any one of the preceding claims, wherein for each pre-masking formulation, the content of one or more ions or impurities in the pre-masking formulation is independently lower than the content in the aqueous initial formulation, or wherein each pre-masking formulation is substantially free of one or more ions and / or impurities present in the aqueous initial formulation, or wherein each pre-masking formulation is substantially free of all ions and / or impurities present in the aqueous initial formulation, and / or wherein the solvent of the pre-masking formulation is water.

26. The method of any of the preceding claims, wherein for each contacting of the ion exchange resin with the post-recovery solvent system, about or at least about 1 to 100 milliliters, such as about 1-50, 1-20, 1-10, 2-10, 5-10, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90 or 100 milliliters of the post-recovery solvent system is independently used per 1 milliliter of resin, or wherein for each contacting of the ion exchange resin with the post-recovery solvent system, about 1-10 milliliters of the post-recovery solvent system is independently used per 1 milliliter of resin.

27. The process according to any one of the preceding claims, wherein the post-recovery solvent system comprises water, or wherein the post-recovery solvent system comprises an alcohol, or wherein the post-recovery solvent system comprises a short-chain alcohol, or wherein the post-recovery solvent system comprises methanol, or wherein the post-recovery solvent system comprises ethanol, or wherein the post-recovery solvent system comprises an organic solvent soluble in water, or wherein the post-recovery solvent system comprises tetrahydrofuran, or wherein the post-recovery solvent system comprises acetone, or wherein the post-recovery solvent system is water, or wherein the post-recovery solvent system is an alcohol, or wherein the post-recovery solvent system is a short-chain alcohol, or wherein the post-recovery solvent system is methanol, or wherein the post-recovery solvent system is ethanol, or wherein the post-recovery solvent system is a mixture of two or more solvents selected from water and short-chain alcohols.

28. The method of any of the preceding claims, wherein the total ion content of each post-recovery solvent system independently does not exceed about 1000, 900, 800, 700, 600, 500, 400, 300, 200, 100, 90, 80, 70, 60, 50, 40, 30, 20, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 ppm (wt / wt), or wherein the total ion content of each post-recovery solvent system independently does not exceed about 100 ppm (wt / wt), or wherein the total ion content of each post-recovery solvent system independently does not exceed about 10 ppm (wt / wt), or wherein each post-recovery solvent system is substantially free of ions and compounds other than solvent, Or wherein for each contacting of the ion exchange resin with the post-recovery solvent system, about or at least about 1 to 100 milliliters, such as about 1-50, 1-20, 1-10, 2-10, 5-10, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90 or 100 milliliters of solvent system (mL / mL) are used per 1 milliliter of resin, or wherein for each contacting of the ion exchange resin with the post-recovery solvent system, about 1-20 milliliters of solvent system (mL / mL) are used per 1 milliliter of resin, or wherein for each contacting of the ion exchange resin with the post-recovery solvent system, about 1-10 milliliters of solvent system (mL / mL) are used per 1 milliliter of resin.

29. The method of any of the preceding claims, wherein after contacting the aqueous initial formulation with the resin(s), the concentration of one or more ions (e.g., inorganic ions (e.g., sulfate, phosphate, pyruvate, lithium, sodium, potassium, ammonium, calcium, magnesium, ferrous (II), ferric (III), aluminum, chloride), and organic ions (e.g., acetate, lactate, malate, succinate, maleate)) independently does not exceed about 1000, 900, 800, 700, 600, 500, 400, 300, 200, 100, 90, 80, 70, 60, 50, 40, 30, 20, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, or 0.1 ppm (w / w).

30. A method according to any one of the preceding claims, wherein the resin is in powder form, or wherein the resin is in spherical form, or wherein the resin is in film form.

31. The process according to any one of the preceding claims, wherein the contacting with the resin is carried out in a batch process, in a column or / and in a continuous flow process.

32. The method of any of the preceding claims, wherein after contacting the aqueous initial formulation with the resin(s), the concentration of one or more ions (e.g., inorganic ions (e.g., sulfate, phosphate, pyruvate, lithium, sodium, potassium, ammonium, calcium, magnesium, ferrous (II), ferric (III), aluminum, chloride), and organic ions (e.g., acetate, lactate, malate, succinate, maleate)) independently does not exceed about 100 ppm (w / w), and / or wherein after contacting the aqueous initial formulation with the resin(s), K + The concentration of K is no more than 200, 100, 50, 20, 10, 5, 1 or 0.5 ppm, and / or wherein after contacting the aqueous initial formulation with the resin(s), K is less than 0.1 ppm compared to the aqueous initial formulation. + The content of is reduced by about or at least about 90% or at least about 99%; and / or wherein after contacting the aqueous initial formulation with the resin(s).

33. A method according to any one of the preceding claims, wherein Mg 2+ ppm, or wherein after contacting the aqueous initial formulation with the resin(s), Mg is less than or equal to 200, 100, 50, 20, 10, 5, 1 or 0.5 ppm compared to the aqueous initial formulation. 2+ The content of is reduced by about or at least about 90% or at least about 99%.

34. The method of any one of the preceding claims, wherein after contacting the aqueous initial formulation with the resin(s), the concentration of pyruvic acid does not exceed 200, 100, 50, 20, 10, 5, 1 or 0.5 ppm, and / or wherein after contacting the aqueous initial formulation with the resin(s), the content of pyruvic acid is reduced by about or at least about 90% or at least about 99% compared to the aqueous initial formulation; and / or 35. A method according to any one of the preceding claims, wherein after contacting the aqueous initial formulation with the resin(s), SO 2- The concentration of SO4 does not exceed 200, 100, 50, 20, 10, 5, 1 or 0.5 ppm, and / or wherein after contacting the aqueous initial formulation with the resin(s), the SO4 2- The content of is reduced by about or at least about 90% or at least about 99%.

36. A method according to any one of the preceding claims, wherein after contacting the aqueous initial formulation with the resin(s), a phosphate (H2PO4 - 、HPO4 2- and / or PO4 3- ) does not exceed a concentration of 200, 100, 50, 20, 10, 5, 1 or 0.5 ppm, and / or wherein after contacting the aqueous initial formulation with the resin(s), the phosphate (H2PO4) content is less than 1 ppm compared to the aqueous initial formulation. - 、HPO4 2- and / or PO4 3- ) content is reduced by about or at least about 90% or at least about 99%.

37. The method according to any one of the preceding claims, comprising preparing the aqueous initial formulation by fermentation, and / or comprising devitalizing biomass.

38. The method according to any one of the preceding claims, comprising preparing the aqueous initial formulation by fermentation, wherein the preparation step comprises centrifugation, continuous centrifugation, filtration, microfiltration, nanofiltration and / or membrane filtration, optionally wherein the pore size is about 10 μm or less, and / or wherein the filter membrane is in the shape of a flat sheet, a hollow tube fiber, a tube, a spiral or a pleated shape.

39. A method according to any one of the preceding claims, comprising evaporating water from the preparation obtained after contacting the aqueous initial preparation with an ion exchange resin and / or comprising evaporating water from the preparation obtained after contacting the aqueous initial preparation with an ion exchange resin under vacuum.

40. The method according to any one of the preceding claims, further comprising distilling to remove components having a boiling point lower than the diol compound, and / or comprising distilling the diol compound from a composition comprising the diol compound, and / or wherein the distillation is performed under vacuum.

41. A process according to any one of the preceding claims, comprising performing a refining, and / or comprising performing a refining after evaporation and before distillation, optionally wherein the refining reduces the content of one or more salts, optionally wherein the refining comprises contacting with a cation exchange resin, optionally wherein the refining comprises contacting with an anion exchange resin, and / or optionally wherein the refining comprises contacting with a porous material, optionally wherein the refining comprises contacting with activated carbon.

42. A method according to any one of the preceding claims, comprising decolorizing the diol compound preparation, optionally wherein decolorizing comprises hydrogenation; and / or wherein decolorizing comprises contacting with a porous material, optionally wherein decolorizing comprises contacting with activated carbon.

43. A method according to any preceding claim, comprising deodorizing the diol compound preparation, optionally wherein deodorizing comprises hydrogenation; and / or wherein deodorizing comprises contacting with a porous material, optionally wherein deodorizing comprises contacting with activated carbon.

44. A diol compound preparation prepared by a process comprising the method of any preceding claim.

45. A method of preparing a solvent, acrylate, polymer, polyurethane, polyester, adhesive, plasticizer or coating, comprising: There is provided a diol compound preparation according to claim 45, The diol compound is converted into the solvent, acrylate, polymer, polyurethane, polyester, adhesive, plasticizer or coating.

46. ​​Use of the diol compound preparation according to claim 45 in the preparation of solvents, acrylates, polymers, polyurethanes, polyesters, adhesives, plasticizers or coatings.

47. A method for identifying whether a resin is suitable for purifying an aqueous initial formulation comprising a diol compound, wherein: The diol compound contains 5 to 12 carbon atoms, and wherein the aqueous initial formulation comprises greater than 50% water; The method includes: It is determined whether the particle size, crosslinking density, kind of functional group, functional group density, and hydrophilicity of the resin are within suitable or desired ranges, or have suitable or desired properties.

48. A method of identifying the suitability of a resin for purifying an aqueous initial formulation comprising a diol compound, comprising using the resin in a method as claimed in any one of claims 2 to 48 and assessing the loss of the diol compound during the ion exchange purification process.

49. The method of any of the preceding claims, wherein the loss of the diol compound during the ion exchange process does not exceed about 5%, about 4%, about 3%, about 2%, or about 1%.

50. The method of any one of claims 48 to 49, wherein the resin is determined to be suitable.

51. The method of any one of the preceding claims, wherein the loss of diol compound without pre-masking and pre-recovery is about or at least about 1.5, 2, 3, 4, 5, 6, 7, 8, 9 or 10 times the loss without pre-masking and without pre-recovery.

52. A method for identifying whether a resin is suitable for purifying an aqueous initial formulation comprising a diol compound, wherein: The diol compound contains 5 to 12 carbon atoms, and wherein the aqueous initial formulation comprises greater than 50% water; The method includes: contacting the resin with the aqueous initial formulation; evaluating retention of the diol compound on the resin; It was determined that retention of the diol compound was reduced compared to that observed using the hydrophobic resin under otherwise comparable conditions.

53. A purified diol compound preparation wherein the diol compound is present in an amount of about or at least about 50% to 100% or more, or about or at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, or 100 times the amount of the diol compound in the aqueous starting preparation from which the diol compound was purified; or A purified diol compound preparation wherein the pyruvic acid content is at least 10 times lower than the pyruvic acid content of the aqueous preparation from which the diol compound was purified; or A purified diol compound preparation wherein the phosphate content is at least 10 times lower than the phosphate content of the aqueous initial preparation from which the diol compound was purified; or A purified diol compound preparation wherein the sulfate content is at least 10 times lower than the sulfate content of the aqueous initial preparation from which the diol compound was purified; or A purified diol compound preparation wherein the potassium content is at least 10 times lower than the potassium content of the aqueous initial preparation from which the diol compound was purified; or A purified diol compound preparation wherein the magnesium content is at least 10 times lower than the magnesium content of the aqueous initial preparation from which the diol compound was purified.

54. The method or formulation of any of the preceding claims, wherein the diol compound contains from about 5 to 12 carbon atoms; or wherein the diol compound has L(OH) n The structure of L is C 5-12 or C 5-8 A hydrocarbon moiety, n is 2 or 3, optionally wherein n is 2, and optionally wherein L is linear or L is branched, and optionally wherein L is saturated or partially unsaturated; or wherein the diol compound has HO(CH2) m OH structure, wherein m is 5-12 or 5-8, or wherein the diol compound is HO(CH2)5OH, HO(CH2)6OH, HO(CH2)7OH, HO(CH2)8OH, HO(CH2)9OH, HO(CH2) 10 OH, HO(CH2) 11 OH or HO(CH2) 12 OH.

55. The method or formulation of any one of claims 2 to 54, wherein the diol compound is HO(CH2)6OH.

56. The method or formulation of any one of embodiments 1 to 235.

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