Feed purification method

Abstract

A method of separating chemical impurities from a feed includes an ion exchange chromatography separation step to remove a first impurity from the feed and an ion exchange adsorption-desorption separation step to remove a second impurity from the feed. The separation method results in the separation and removal of unwanted impurities present in the feed from a target compound and provides a high yield of the target compound for further downstream processing.

Description

[0001] FEED PURIFICATION METHOD

[0002] TECHNICAL FIELD

[0003] The disclosure relates to a method of purifying a starting material feed by removing at least one undesired chemical compound present in the feed from at least one desired chemical compound in the feed. The disclosure relates to a method of purifying a starting material feed by removing at least one undesired organic acid contained in the feed from at least one desired organic acid in the feed.

[0004] BACKGROUND

[0005] The cyclohexanecarboxylic acid is used in chemical reactions to prepare flavor and taste masking compounds for use in connection with food and pharmaceutical products.

[0006] Cyclohexanecarboxylic acid may be prepared by a fermentation method. The fermentation broth containing the cyclohexane carboxylic acid may also contain further aromatic acids 1 -cyclohexene- 1 -carboxylic acid and benzoic acid and aliphatic carboxylic acids crotonic acid and acetic acid. These other organic acids have the following chemical structures:

[0007] Cyclohexanec 1-cyclohexene-l- Benzoic acid Crotonic acid Acetic acid arboxylic acid carboxylic acid

[0008] These aromatic and aliphatic organic acids present in the fermentation broth are considered undesired impurities as they interfere with downstream esterification reactions of cyclohexane carboxylic acid to prepare flavor and taste masking compounds. The organic acids pose a significant challenge due to their structural similarities to cyclohexanecarboxylic acid and are difficult to separate from cyclohexanecarboxylic acid. What is needed in the art is a method of purifying a feed containing cyclohexanecarboxylic acid among other aromatic and / or aliphatic organic carboxylic acids that has a shorter process cycle time, consumes less energy, and consumes less organic solvent.

[0009] SUMMARY OF ILLUSTRATIVE EMBODIMENTS

[0010] According to a first illustrative embodiment, disclosed is a method of purifying a feed comprising an ion exchange chromatography separation step to remove at least a first impurity compound from the feed; and an ion exchange adsorption-desorption step to remove at least a second impurity compound from the feed.

[0011] According to a second illustrative embodiment, disclosed is a purified feed produced by the process of an ion exchange chromatography separation step to remove at least a first impurity compound from the feed and an ion exchange adsorption-desorption step to remove at least a second impurity compound from the feed.

[0012] According to a third illustrative embodiment, disclosed is a method of purifying a fermentation broth comprising an ion exchange chromatography separation step to remove at least a first impurity compound from the fermentation broth; and an ion exchange adsorptiondesorption step to remove at least a second impurity compound from the fermentation broth.

[0013] According to a fourth illustrative embodiment, disclosed is a purified fermentation broth produced by the process of an ion exchange chromatography separation step to remove at least a first impurity compound from the feed and an ion exchange adsorption-desorption step to remove at least a second impurity compound from the fermentation broth.

[0014] According to a fifth illustrative embodiment, disclosed is a method comprising (a) preparing a purified feed comprising (a-1) an ion exchange chromatography separation step to remove at least a first impurity compound from the feed and (a-2) an ion exchange adsorptiondesorption step to remove at least a second impurity compound from the feed, and (b) a downstream esterification reaction using purified feed. According to a sixth illustrative embodiment, disclosed is a method comprising (a) preparing a purified fermentation broth comprising (a-1) an ion exchange chromatography separation step to remove at least a first impurity compound from the fermentation broth and (a-2) an ion exchange adsorption-desorption step to remove at least a second impurity compound from the fermentation broth, and (b) a downstream esterification reaction using purified fermentation broth.

[0015] According to a seventh illustrative embodiment, disclosed is the use of a purified feed prepared according to a method comprising (a) preparing a purified feed comprising (a-1) an ion exchange chromatography separation step to remove at least a first impurity compound from the feed and (a-2) an ion exchange adsorption-desorption step to remove at least a second impurity compound from the feed in an esterification reaction.

[0016] According to an eighth illustrative embodiment, disclosed is the use of a purified feed prepared according to a method comprising (a) preparing a purified fermentation broth comprising (a-1) an ion exchange chromatography separation step to remove at least a first impurity compound from the fermentation broth and (a-2) an ion exchange adsorptiondesorption step to remove at least a second impurity compound from the fermentation broth in an esterification reaction.

[0017] According to a ninth illustrative embodiment, disclosed is the use of a purified feed prepared according to a method comprising (a) preparing a purified feed comprising (a-1) an ion exchange chromatography separation step to remove at least a first impurity compound from the feed and (a-2) an ion exchange adsorption-desorption step to remove at least a second impurity compound from the feed to prepare an esterification reaction product.

[0018] According to a tenth illustrative embodiment, disclosed is the use of a purified feed prepared according to a method comprising (a) preparing a purified fermentation broth comprising (a-1) an ion exchange chromatography separation step to remove at least a first impurity compound from the fermentation broth and (a-2) an ion exchange adsorptiondesorption step to remove at least a second impurity compound from the fermentation broth to prepare an esterification reaction product.

[0019] According to an eleventh illustrative embodiment, disclosed is an esterification product prepared by the reaction of a purified feed prepared according to a method comprising (a) preparing a purified feed comprising (a-1) an ion exchange chromatography separation step to remove at least a first impurity compound from the feed and (a-2) an ion exchange adsorptiondesorption step to remove at least a second impurity compound from the feed with another chemical reactant sufficient to form the esterification reaction product.

[0020] According to a twelfth illustrative embodiment, disclosed is an esterification product prepared by the reaction of a purified fermentation broth prepared according to a method comprising (a) preparing a purified fermentation broth comprising (a-1) an ion exchange chromatography separation step to remove at least a first impurity compound from the fermentation broth and (a-2) an ion exchange adsorption-desorption step to remove at least a second impurity compound from the fermentation broth with another chemical reactant sufficient to form the esterification reaction product.

[0021] BRIEF DESCRIPTION OF ILLLUSTRATIVE DRAWINGS

[0022] FIGURE 1 is a flow chart for an illustrative embodiment of the disclosed separation method.

[0023] FIGURE 2 is a flow chart for another illustrative embodiment of the disclosed separation method.

[0024] FIGURE 3 is a graph depicting the separation of benzoic acid from a fermentation broth by an ion-exchange chromatography separation step.

[0025] FIGURE 4 is a graph depicting the separation of crotonic acid from a fermentation broth by an ion-exchange adsorption / desorption separation step. DETAILED DESCRIPTION OF ILLUSTATIVE EMBODIMENTS

[0026] The following text sets forth a broad description of numerous different embodiments of the present disclosure. The description is to be construed as exemplary only and does not describe every possible embodiment since describing every possible embodiment would be impractical, if not impossible. It will be understood that any feature, characteristic, component, composition, ingredient, product, step or methodology described herein can be deleted, combined with or substituted for, in whole or part, any other feature, characteristic, component, composition, ingredient, product, step or methodology described herein. Numerous alternative embodiments could be implemented, using either current technology or technology developed after the filing date of this patent, which would still fall within the scope of the claims.

[0027] The terms “comprises,” “comprising,” “has,” “having,” “includes,” “including,” “contains,” “containing,” or any other variation are open-ended and are intended to cover a non-exclusive inclusion of elements, such that an article, apparatus, compound, composition, combination, method, or process that “comprises,” “has,” or “includes,” or “contains” a recited list of elements does not include only those elements but may include other elements not expressly listed, recited or written in the specification or claims. An element or feature proceeded by the language “comprises . . .a,” “contains . . . a,” “has . . . a,” or “includes . . .a” does not, without more constraints, preclude the existence or inclusion of additional elements or features in the article, apparatus, compound, composition, combination, method, or process that comprises, contains, has, or includes the element or feature.

[0028] The terms “a” and “an” are defined as one or more unless expressly stated otherwise or constrained by other language herein. An element or feature proceeded by “a” or “an” may be interpreted as one of the recited element or feature, or more than one of the element or feature.

[0029] The terms “about,” “approximately,” “essentially,” “substantially,” any other version thereof, or any other similar relative term, or similar term of approximation, are defined as being close to as understood by one having ordinary skill in the art. By way of non-limiting, illustrative embodiments, these terms are defined to be within 20 % of a recited value, or defined to be within 10% of a recited value, or defined to be within 5% of a recited value, or defined to be within 4% of a recited value, or defined to be within 3% of a recited value, or defined to be within 2% of a recited value, or defined to be within 1% of a recited value, of defined to be within 0.75% of a recited value, or defined to be within 0.5% of a recited value, or defined to be within 0.25% of a recited value, or defined to be within 0.1% of a recited value.

[0030] It should be understood that when an amount in weight percent is described in the present disclosure, it is intended that any and every amount within the range, including the end points, is to be considered as having been expressly disclosed. For example, the disclosure of "a range of from about 1 to about 100" is to be read as indicating each and every possible number along the continuum between about 1 and about 100. It is to be understood that the inventors appreciate and understand that any and all data points within the range are to be considered to have been disclosed and specified, and that the inventors have possession of the entire range and all points within the range.

[0031] When a concentration is expressed as “ppm”, the concentration is parts per million by weight based on the total weight of a component, compound, composition, or consumable. It should be understood that when a range of values is described in ppm, it is intended that any and every value within the range, including the end points, is to be considered as having been disclosed. For example, “a range of from 1 ppm to 1000 ppm” is to be read as indicating each and every possible number along the continuum between 1 and 1000. It is to be understood that the inventors appreciate and understand that any and all values within the range are to be considered to have been disclosed and specified, and that the inventors have possession of the entire range and all the values within the range. For the avoidance of doubt, alternative and optional features indicated for a given aspect, component, feature, or parameter of the invention should, unless the context indicates otherwise, be regarded as having been disclosed in combination with any and all other alternative or optional features and the like as indicated for the same or other aspects, features and parameters of the invention.

[0032] Disclosed is a method of purifying a fermentation broth containing at least one impurity to be removed. The method comprises an ion exchange chromatography separation step to remove at least a first impurity compound from the fermentation broth and an ion exchange adsorption-desorption step to remove at least a second impurity compound from the fermentation broth.

[0033] According to certain illustrative embodiments, the at least one impurity contained in the fermentation broth to be removed comprises at least one aromatic carboxylic acid, at least one aliphatic carboxylic acid and combinations thereof. According to certain illustrative embodiments, the at least one impurity contained in the fermentation broth to be removed comprises a combination of at least one aromatic carboxylic acid and at least one aliphatic carboxylic acid.

[0034] By way of illustration, and not in limitation, the at least one aromatic carboxylic acid contained in the fermentation broth comprises at least one of cyclohexanecarboxylic acid, 1- cyclohexene-1 -carboxylic acid, and benzoic acid, and wherein the at least one aliphatic carboxylic acid contained in the fermentation broth comprises at least one of crotonic acid and acetic acid. According to certain illustrative embodiments, the at least one aromatic carboxylic acid contained in the fermentation broth comprises cyclohexanecarboxylic acid, 1- cyclohexene-1 -carboxylic acid, and benzoic acid, and wherein the at least one aliphatic carboxylic acid contained in the fermentation broth comprises crotonic acid and acetic acid. According to certain embodiments, the fermentation broth comprises from about 0.001 weight percent to about 0.01 weight percent cyclohexanecarboxylic acid, from about 0.0001 weight percent to about 0.005 weight percent 1-cyclohexene-l-carboxylic acid, from about 0.002 weight percent to about 0.01 weight percent benzoic acid, from about 0.001 weight percent to about 0.01 weight percent crotonic acid, and from about 0.02 weight percent to about 0.05 weight percent acetic acid.

[0035] According to certain embodiments, the fermentation broth comprises from about 0.0015 weight percent to about 0.01 weight percent cyclohexanecarboxylic acid, from about 0.00015 weight percent to about 0.004 weight percent 1-cyclohexene-l-carboxylic acid, from about 0.0025 weight percent to about 0.01 weight percent benzoic acid, from about 0.002 weight percent to about 0.005 weight percent crotonic acid, and from about 0.025 weight percent to about 0.04 weight percent acetic acid.

[0036] According to certain embodiments, the fermentation broth comprises from about 0.0018 weight percent to about 0.007 weight percent cyclohexanecarboxylic acid, from about 0.00013 weight percent to about 0.003 weight percent 1-cyclohexene-l-carboxylic acid, from about 0.0028 weight percent to about 0.011 weight percent benzoic acid, from about 0.003 weight percent to about 0.007 weight percent crotonic acid, and from about 0.022 weight percent to about 0.031 weight percent acetic acid.

[0037] According to certain illustrative embodiments, the first chemical compound of interest removed by the ion exchange resin chromatography separation step comprises benzoic acid.

[0038] According to certain illustrative embodiments, the ion exchange resin utilized in the ion exchange resin chromatography separation step to remove the at least a first compound of interest from the fermentation broth comprises a polyacrylate backbone.

[0039] According to certain illustrative embodiments, the ion exchange resin utilized in the ion exchange resin chromatography separation step to remove the at least a first compound of interest from the fermentation broth comprises a polyacrylate backbone and a weak base functionality.

[0040] According to certain illustrative embodiments, the ion exchange resin utilized in the ion exchange resin chromatography separation step to remove the at least a first compound of interest from the fermentation broth comprises a polyacrylate backbone having a uniformity coefficient of about 1.0 to about 1.5.

[0041] According to certain illustrative embodiments, the ion exchange resin utilized in the ion exchange resin chromatography separation step to remove the at least a first compound of interest from the fermentation broth comprises a polyacrylate backbone having a uniformity coefficient from about 1.0 to about 1.4, or from about 1.0 to about 1.3, or from about 1.0 to about 1.2, or from about 1.0 to about 1.1.

[0042] According to certain illustrative embodiments, the ion exchange resin utilized in the ion exchange resin chromatography separation step to remove the at least a first compound of interest from the fermentation broth comprises a polyacrylate backbone having a uniformity coefficient of about 1.0 to about 1.5 and a weak base functionality. According to certain illustrative embodiments, the ion exchange resin utilized in the ion exchange resin chromatography separation step to remove the at least a first compound of interest from the fermentation broth comprises a polyacrylate backbone having a uniformity coefficient of about 1.0 to about 1.1 and a weak base functionality.

[0043] According to certain illustrative embodiments, the ion exchange resin in polyatomic anion form. Without limitation, and only by way of illustration, the polyatomic anion is a sulfate anion.

[0044] According to certain illustrative embodiments, the ion exchange resin utilized in the ion exchange resin chromatography separation step to remove the benzoic acid from the fermentation broth comprises a polyacrylate backbone and a weak base functionality. Without limitation, the polyacrylate backbone and functionality of the ion-exchange resin is shown in

[0045] (I) below:

[0046] Polyacrylal® backhoe Weak base functionality

[0047] (I)

[0048] The flow rate of the fermentation broth containing the first chemical compound to be removed from the broth by the ion exchange resin chromatography separation step is from about 0.2 BV / h to about 6 BV / h, or from about 0.5 BV / h to about 4 BV / h, or from about 1 BV / h to about 3 BV / h.

[0049] According to certain embodiments, the ion exchange resin chromatography separation step does not utilize an organic solvent.

[0050] According to the disclosed separation method, a second compound of interest is removed from the fermentation broth. The second compound of interest is removed from the fermentation broth by an ion exchange resin adsorption-desorption separation step. According to certain illustrative embodiments, the second compound of interest removed from the fermentation broth by the ion exchange resin adsorption-desorption separation step is crotonic acid. According to certain illustrative embodiments, the second compound of interest removed from the fermentation broth by the ion exchange resin adsorption-desorption separation step is crotonic acid.

[0051] The flow rate of the fermentation broth through the ion-exchange resin adsorptiondesorption separation step to remove the at least second compound of interest from the fermentation broth is from about 0.5 BV / h to about lOBV / h, or from about 1 BV / h to about 8

[0052] BV / h, or from about 2 BV / h to about 6 BV / h.

[0053] According to certain illustrative embodiments, the ion-exchange resin utilized in the ion exchange resin adsorption-desorption separation step to remove at least a second compound of interest from the fermentation broth comprises a polyacrylate or polystyrene backbone. According to certain illustrative embodiments, the ion exchange resin utilized in the ion exchange resin adsorption-desorption separation step to remove at least a second compound of interest from the fermentation broth comprises a polyacrylate backbone.

[0054] At least one desorbent liquid is flowed through the ion-exchange resin during the ionexchange resin adsorption-desorption separation step to desorb the adsorbed second compound of interest. Without limitation, alcohol, water, and mixtures thereof. According to certain embodiments, the desorbent liquid used in the ion-exchange resin adsorption-desorption separation step comprising an ethanol mixture in water. Without limitation, a suitable desorbent liquid comprising ethanol in water comprises less than about 60 percent ethanol in water to desorb crotonic acid from the ion-exchange resin. According to certain embodiments, a suitable desorbent liquid comprising ethanol in water comprises greater than about 30 percent to less than about 60 percent ethanol in water to desorb crotonic acid from the ion-exchange resin. According to other suitable embodiments, the desorbent liquid comprising ethanol in water comprises greater than 30 percent to about 55 percent ethanol in water, or from about 30 to about 50 percent ethanol in water, or from about 30 to about 45 percent ethanol in water, or from about 30 to about 40 percent ethanol in water, or from about 30 to about 35 percent ethanol in water, or from about 35 to about 60 percent ethanol in water, or from about 35 to about 55 percent ethanol in water, or from about 35 to about 50 percent ethanol in water, or from about 35 to about 45 percent ethanol in water, or from about 35 to about 40 percent ethanol in water, or from about 40 to about 60 percent ethanol in water, or from about 40 to about 55 percent ethanol in water, or from about 40 to about 50 percent ethanol in water, or from about 45 to about 45 percent ethanol in water, or from about 40 to about 60 percent ethanol in water, or from about 40 to about 55 percent ethanol in water, or from about 40 to about 50 percent ethanol in water, or from about 40 to about 45 percent ethanol in water, or any range between greater than about 30 percent to less than about 60 percent ethanol in water.

[0055] According to other embodiments, the desorbent liquid comprising an ethanol in water mixture comprises greater than 60 percent ethanol in water to desorb organic acid compounds other than crotonic acid from the fermentation broth.

[0056] According to certain illustrative embodiments, the ion-exchange resin chromatography step used to separate benzoic acid from the other organic acid compounds present in the starting fermentation broth removes at least 90 weight percent or greater of the benzoic acid present in the fermentation broth starting material. According to certain embodiments, the ion-exchange resin chromatography step used to separate benzoic acid from the other organic acid compounds present in the starting fermentation broth removes at least 91 weight percent or greater of the benzoic acid present in the fermentation broth starting material, or 92 weight percent or greater of the benzoic acid present in the fermentation broth starting material, or 93 weight percent or greater of the benzoic acid present in the fermentation broth starting material, or 94 weight percent or greater of the benzoic acid present in the fermentation broth starting material, or 95 weight percent or greater of the benzoic acid present in the fermentation broth starting material, or 96 weight percent or greater of the benzoic acid present in the fermentation broth starting material, or 97 weight percent or greater, or 98 weight percent or greater of the benzoic acid present in the fermentation broth starting material, or 99 weight percent or greater of the benzoic acid present in the fermentation broth starting material, or 99.1 weight percent or greater of the benzoic acid present in the fermentation broth starting material, or 99.2 weight percent or greater of the benzoic acid present in the fermentation broth starting material, or 99.3 weight percent or greater of the benzoic acid present in the fermentation broth starting material, or 99.4 weight percent or greater of the benzoic acid present in the fermentation broth starting material, or 99.5 weight percent or greater of the benzoic acid present in the fermentation broth starting material, or 99.6 weight percent or greater of the benzoic acid present in the fermentation broth starting material, or 99.7 weight percent or greater of the benzoic acid present in the fermentation broth starting material, or 99.8 weight percent or greater of the benzoic acid present in the fermentation broth starting material, or 99.9 weight percent or greater of the benzoic acid present in the fermentation broth starting material, 100 weight percent of the benzoic acid present in the fermentation broth starting material.

[0057] According to certain illustrative embodiments, the ion-exchange resin adsorptiondesorption separation step used to separate crotonic acid from the other organic acid compounds present in the starting fermentation broth removes at least 90 weight percent or greater of the crotonic acid present in the fermentation broth starting material. According to certain embodiments, the ion-exchange resin adsorption-desorption separation step used to separate crotonic acid from the other organic acid compounds present in the starting fermentation broth removes 91 weight percent or greater of the crotonic acid present in the fermentation broth starting material, or 92 weight percent or greater of the crotonic acid present in the fermentation broth starting material, or 93 weight percent or greater of the crotonic acid present in the fermentation broth starting material, or 94 weight percent or greater of the crotonic acid present in the fermentation broth starting material, or 95 weight percent or greater of the crotonic acid present in the fermentation broth starting material, or 96 weight percent or greater of the crotonic acid present in the fermentation broth starting material, or 97 weight percent or greater of the crotonic acid present in the fermentation broth starting material, or 98 weight percent or greater of the crotonic acid present in the fermentation broth starting material, of the crotonic acid present in the fermentation broth starting material, or 99 weight percent or greater of the crotonic acid present in the fermentation broth starting material, or 99.1 weight percent or greater of the crotonic acid present in the fermentation broth starting material, or 99.2 weight percent or greater of the crotonic acid present in the fermentation broth starting material, or 99.3 weight percent or greater of the crotonic acid present in the fermentation broth starting material, or 99.4 weight percent or greater of the crotonic acid present in the fermentation broth starting material, or 99.5 weight percent or greater of the crotonic acid present in the fermentation broth starting material, or 99.6 weight percent or greater of the crotonic acid present in the fermentation broth starting material, or 99.7 weight percent or greater of the crotonic acid present in the fermentation broth starting material, or 99.8 weight percent or greater of the crotonic acid present in the fermentation broth starting material, or 99.9 weight percent or greater of the crotonic acid present in the fermentation broth starting material, 100 weight percent of the crotonic acid contained in the fermentation broth.

[0058] According to certain illustrative embodiments of the separation method, the percent yield of cyclohexane carboxylic acid resulting from the separation method comprising the first ion-exchange resin chromatography separation step and the second ion-exchange adsorptiondesorption separation step is at least 80 percent, or at least 85 percent, or at least 90 percent, or at least 91 percent, or at least 92 percent, or at least 93 percent, or at least 94 percent, or at least 95 percent.

[0059] According to certain illustrative embodiments, the disclosed separation method comprises the optional step of removing at least one of cells and cell debris from the fermentation broth before the ion-exchange resin chromatography and ion exchange resin adsorption-desorption separation steps. According to certain embodiments, the optional step of removing at least one of cells and cell debris from the fermentation broth before the ion exchange resin chromatography and ion exchange adsorption-desorption steps comprises filtering or centrifugation of the fermentation broth. The step of filtering or centrifuging the fermentation broth to remove the cell and / or cell debris is conducted for a period of time from about 0.1 hour to about 4 hours, or from about 1 hour to about 2 hours, or from about 0.4 hour to about 0.8 hour.

[0060] According to certain embodiments, the separation method comprises optionally removing at least a portion of the water from the fermentation broth before the ion exchange resin chromatography and ion exchange adsorption steps. According to certain embodiments, the optional step of removing a portion of the water from the fermentation broth is conducted after the optional step of removing the cells and / or cell debris and before the first ion-exchange resin chromatography separation step. Without limitation, the optional step of removing at least a portion of the water from the fermentation broth before the ion exchange resin chromatography and ion exchange adsorption steps comprises conducting reverse osmosis on the fermentation broth by passing the fermentation broth through a reverse osmosis membrane. The step of conducting reverse osmosis on the fermentation broth is conducted for a period of time from about 0.5 hour to about 4 hours, or from about 1 hour to about 3 hours, or from about 1.2 hours to about 2 hours. According to certain embodiments, the above time ranges for conducting the reverse osmosis step on the fermentation broth is based on an 8 inch reverse osmosis filter membrane and a lOOOL fermentation broth.

[0061] According to certain embodiments, the separation method comprises conducting the optional step of removing additional water from the fermentation broth following the second ion-exchange resin adsorption-desorption separation step. According to certain embodiments, the optional step of removing additional water from the fermentation broth following the second ion-exchange resin adsorption-desorption separation step comprises a distillation step to remove water from the fermentation broth after the ion exchange resin chromatography and ion exchange adsorption steps. According to certain embodiments, the separation method comprises an optional drying step of the fermentation broth after the second ion-exchange resin adsorption-desorption separation step or the optional distillation step.

[0062] FIGURE 1 depicts a process flow an illustrative embodiment (10) of the presently disclosure separation method. According to illustrative embodiment (10), a fermentation broth comprising a blend of aromatic organic acids and aliphatic organic acids is subject to separation step (20) to remove cells and cell debris from the upstream fermentation process. The fermentation broth includes at least cyclohexanecarboxylic acid, 1 -cyclohexene- 1 -carboxylic acid, benzoic acid, crotonic acid, and acetic acid. The fermentation broth is then subjected to a water removal step (30) passing the fermentation broth through a reverse osmosis membrane. According to certain embodiments, the volume of the fermentation broth following the water removal step (30) is in the range of about 5 to about 10 times less than the volume of the fermentation broth prior to the water removal step (30). The fermentation broth following the water removal step (30) is subjected to an ion-exchange chromatography separation step (40) to remove at least a portion of the benzoic acid from the fermentation broth. Following the ionexchange chromatography separation step (40), the fermentation broth is subjected to an ionexchange adsorption / desorption separation step (50) to remove at least a portion of the crotonic acid from the fermentation broth. The process (10) may include optional additional water removal step (60) and optional drying step (70).

[0063] FIGURE 2 depicts a process flow another illustrative embodiment (110) of the presently disclosure separation method. According to illustrative embodiment (110), a fermentation broth comprising a blend of aromatic organic acids and aliphatic organic acids is subject to separation step (120) to remove cells and cell debris from the upstream fermentation process. The fermentation broth includes at least cyclohexanecarboxylic acid, 1 -cyclohex ene- 1 -carboxylic acid, benzoic acid, crotonic acid, and acetic acid. The fermentation broth is then subjected to a water removal step (130) passing the fermentation broth through a reverse osmosis membrane. The fermentation broth with a reduced volume following water removal step (130) is subjected to an ion-exchange chromatography separation step (140) to remove at least a portion of the benzoic acid from the fermentation broth. Following the ion-exchange chromatography separation step (140), the fermentation broth is subjected to an ion-exchange adsorption / desorption separation step (150) to remove at least a portion of the crotonic acid from the fermentation broth. The ion-exchange adsorption / desorption separation step (150) also removes at least a portion of the acetic acid from the fermentation broth. The process (110) may include optional additional water removal step (160) and optional drying step (170). The product of the two-step separation process is used in a downstream esterification reaction (180) in which the purified cyclohexanecarboxylic acid species is reacted with an alcohol to form the desired ester reaction product.

[0064] EXAMPLES

[0065] Example 1A

[0066] The removal of benzoic acid from a fermentation broth starting material containing cyclohexanecarboxylic acid, 1 -cyclohexene- 1 -carboxylic acid, benzoic acid, crotonic acid, and acetic acid by the presently disclosed ion-exchange chromatography separation was evaluated. 100ml of an ion-exchange chromatography resin having a polyacrylate backbone was loaded into a Biotage resin column and the resin was rinsed with 400ml of deionized water. An 8ml feed of a fermentation broth containing cyclohexanecarboxylic acid, 1 -cyclohexene- 1- carboxylic acid, benzoic acid, crotonic acid, and acetic acid was injected into the resin column and was eluted with 2g / L H2SO4 at a flow rate of 2ml / min. Fractions were collected every 10ml for a total of 300ml (3BV). The fractions were analyzed by HPLC with cyclohexanecarboxylic acid, 1 -cyclohexene- 1 -carboxylic acid detected at a wavelength of 214 nm and benzoic acid and crotonic acid detected at a wavelength of 254 nm. Chromatograms were generated and the separation resolution factor R was calculated for benzoic acid. The results for Example 1 A are shown in Table 1 A below. The results indicate that the use of the IER chromatography separation step to remove benzoic acid from the fermentation broth starting material achieves removal of 99% of the benzoic acid from the fermentation broth starting material and a results in a % yield of 90% of cyclohexanecarboxylic acid in only 2 hours of process time.

[0067] TABLE 1A

[0068] IER = ion-exchange chromatography

[0069] Example IB

[0070] The removal of crotonic acid from a fermentation broth starting material containing cyclohexanecarboxylic acid, 1 -cyclohexene- 1 -carboxylic acid, benzoic acid, crotonic acid, and acetic acid by the presently disclosed ion-exchange adsorption-desorption separation was evaluated. 100ml of a polymeric adsorbent resin having a poly acrylate backbone was loaded into a Biotage resin column and the resin was rinsed with 400ml of deionized water. A 400ml feed of a fermentation broth containing cyclohexanecarboxylic acid, 1 -cyclohexene- 1- carboxylic acid, benzoic acid, crotonic acid, and acetic acid was loaded into the resin column and was eluted with 150ml of 30% ethanol in water solution (ie, first mobile phase desorbent) at a flow rate of 2ml / min followed by further elution with 250ml of 60% ethanol in water solution (ie, second mobile phase desorbent) at a flow rate of 2ml / min. The fermentation broth feed was rinsed with 300ml of deionized water prior to elution with the ethanol in water solutions. Fractions were collected every 10ml for a total of 400ml (4BV). The fractions were analyzed by HPLC with cyclohexanecarboxylic acid, 1 -cyclohexene- 1 -carboxylic acid detected at a wavelength of 214 nm and benzoic acid and crotonic acid detected at a wavelength of 254 nm. Elution of the fermentation broth feed with the 30-60% ethanol in water mobile phase desorbent results in separation of the crotonic acid only from the other organic acids present in the feed. Elution of the fermentation broth feed with greater than 60% ethanol in water mobile phase desorbent results in separation of all other organic acids present in the feed. The 1.5 B V fraction of the elution of the fermentation broth feed with the 30% ethanol in water mobile phase desorbent results in elution of crotonic acid before switching to elution of the feed with the greater than 60% ethanol in water mobile phase desorbent.

[0071] The results are shown in Table IB below. The results indicate that the use of the IER adsorption-desorption separation step to remove crotonic acid from the fermentation broth starting material achieves removal of 10% of the crotonic acid from the fermentation broth starting material and a results in a % yield of 90% of cyclohexanecarboxylic acid in only 6 hours of process time.

[0072] TABLE IB

[0073] IER = ion-exchange chromatography

[0074] FIGURE 3 is a graph depicting the removal of benzoic acid by the ion-exchange resin chromatography separation step (30, 130). The graph shows excellent separation of benzoic acid from cyclohexanecarboxylic acid and crotonic acid. The separation resolution factor R of cyclohexanecarboxylic acid to benzoic acid is 0.98 with a higher R value representing a better separate and a R value of 1 being 100% separation of the compounds.

[0075] FIGURE 4 is a graph depicting the removal of benzoic acid by the ion-exchange resin adsorption / desorption separation step (40, 140). The graph shows excellent separation of crotonic acid from cyclohexanecarboxylic acid. The separation resolution factor R of cyclohexane- carboxylic acid to crotonic acid is 1. While the method of separating compounds been described in connection with various embodiments, it is to be understood that other similar embodiments may be used or modifications and additions may be made to the described embodiments for performing the same function. Furthermore, the various illustrative embodiments may be combined to produce the desired results. Therefore, the disclosed methods, uses, compositions, and consumables should not be limited to any single embodiment, but rather construed in breadth and scope in accordance with the recitation of the appended claims. It will be understood that the embodiments described herein are merely exemplary, and that one skilled in the art may make variations and modifications without departing from the spirit and scope of the invention. All such variations and modifications are intended to be included within the scope of the invention as described hereinabove. Further, all embodiments disclosed are not necessarily in the alternative, as various embodiments of the invention may be combined to provide the desired result.

Claims

CLAIMS1. A method of purifying a fermentation broth comprising: an ion exchange chromatography separation step to remove at least a first impurity compound from the fermentation broth; and an ion exchange adsorption-desorption step to remove at least a second impurity compound from the fermentation broth.

2. The method according to claim 1, wherein the fermentation broth contains a blend of aromatic carboxylic acids and aliphatic carboxylic acids.

3. The method according to claim 2, wherein the aromatic carboxylic acids contained in the fermentation broth comprise cyclohexanecarboxylic acid, 1 -cyclohexene- 1 -carboxylic acid, and benzoic acid and wherein the aliphatic carboxylic acids contained in the fermentation broth comprise crotonic acid and acetic acid.

4. The method of claim 3, wherein the fermentation broth comprises from 0.0018 weight percent to 0.007 weight percent cyclohexanecarboxylic acid, from 0.00013 weight percent to 0.003 weight percent 1 -cyclohexene- 1 -carboxylic acid, from 0.0028 weight percent to 0.011 weight percent benzoic acid, from 0.003 weight percent to 0.007 weight percent crotonic acid, and from 0.022 weight percent to 0.031 weight percent acetic acid.

5. The method of claim 4, wherein the first compound of interest removed by the ion exchange resin chromatography separation step is benzoic acid.

6. The method according to claim 5, wherein the ion exchange resin utilized in the ion exchange resin chromatography separation step to remove at least a first compound of interest from the fermentation broth comprises a polyacrylate backbone and a weak base functionality.

7. The method according to claim 6, wherein the ion exchange resin in polyatomic anion form.

8. The method according to claim 7, wherein the polyatomic anion is a sulfate anion.

9. The method according to claim 6, wherein the flow rate of ion exchange resin chromatography separation step to remove at least a first compound of interest from the fermentation broth is from 0.2 BV / h to 6 BV / h.

10. The method according to claim 8, wherein the ion exchange resin chromatography separation step does not utilize an organic solvent.

11. The method of claim 5, wherein the second compound of interest removed by the ion exchange resin adsorption-desorption separation step is crotonic acid.

12. The method according to claim 1, wherein the flow rate of the ion exchange resin adsorption-desorption separation step to remove at least a second compound of interest from the fermentation broth is from 0.5 BV / h to 10 BV / h.

13. The method according to claim 11, wherein the ion exchange resin utilized in the ion exchange resin adsorption-desorption separation step to remove at least a second compound of interest from the fermentation broth comprises a polyacrylate or polystyrene backbone.

14. The method according to claim 13, wherein the ion exchange resin utilized in the ion exchange resin adsorption-desorption separation step to remove at least a second compound of interest from the fermentation broth comprises the polyacrylate.

15. The method according to claim 14, wherein the concentration of the desorbent is greater than 30 percent to less than 60 percent ethanol in water to desorb crotonic acid.

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