Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
  • C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
  • C07C51/377—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
  • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
  • Y02P20/00—Technologies relating to chemical industry
  • Y02P20/10—Process efficiency

Definitions

• 3-HP 3- hydroxypropionic acid
• CAS No. 503-66-2 3- hydroxypropionic acid
• 3-HP is a highly valuable building block used in the production of a number of chemicals, such as acrylic acid, acrylates, and acrylamide, which can be further converted to a wide range of industrial and consumer products.
• the present invention provides a process of producing acrylic acid, comprising the steps of: (a) providing a fermentation broth comprising 3-HP, or salt thereof; (b) removing a substantial amount of water from said fermentation broth to give a concentrated fermentation broth; (c) extracting said 3-HP from said concentrated fermentation broth with an organic solvent, wherein said organic solvent has a boiling point of less than 170 °C; (d) distilling the i extract from step (c) to give a 3-HP solution comprising high purity 3-HP; (e) vaporizing said 3-HP solution to produce a 3-HP/water vapor; and (f) contacting the 3-HP/water vapor with a catalyst or inert surface area in a fixed bed reactor, thereby converting the 3-HP to acrylic acid.
• the process of producing acrylic acid can further comprise, wherein said high purity 3-HP has purity higher than 90%, or wherein said high purity 3-HP has purity higher than 95%.
• the process of producing acrylic acid can further comprise, wherein a substantial amount of whole cells are removed from said fermentation broth prior to step (a) and can further comprise wherein said substantial amount of whole cells are removed with a centrifuge.
• the process of producing acrylic acid can include, wherein a substantial amount of whole cells are removed from said fermentation broth after step (a) and can further comprise wherein said substantial amount of whole cells are removed with a centrifuge.
• the process of producing acrylic acid can further comprise, wherein said removing a substantial amount of water is performed by evaporation.
• the process of producing acrylic acid can further comprise wherein said evaporation is carried out at a temperature range of 50-150 °C. In another embodiment the process of producing acrylic acid can further comprise wherein said evaporation is carried out at a reduced pressure of 20-1,000 mbar. In another embodiment the process of producing acrylic acid can further comprise wherein said removing a substantial amount of water is performed with mechanical recompression methods. In another embodiment the process of producing acrylic acid can further comprise wherein said removing a substantial amount of water is performed with a thin film
• the process of producing acrylic acid can further comprise, wherein at least 80%>, 90%>, 95%, or 99% of water in said fermentation broth is removed. In another embodiment the process of producing acrylic acid can further comprising separating any resulting solids during or after removing water. In another embodiment the process of producing acrylic acid can further comprise adjusting pH of said concentrated fermentation broth with an acid after step (b). In another embodiment the process of producing acrylic acid can further comprising adjusting pH of said concentrated fermentation broth with an acid after step (b), wherein the acid is sulfuric acid or phosphoric acid. In another embodiment the process of producing acrylic acid can include, further comprising adjusting pH of said concentrated fermentation broth with an acid after step (b) further comprise separating any resulting solids during or after the addition of said acid.
• the process of producing acrylic acid can further comprise wherein said organic solvent is an alcohol solvent.
• said process of producing acrylic acid with an alcohol solvent can include, wherein said alcohol solvent is selected from the group consisting of C1-C12 aliphatic alcohols.
• said process of producing acrylic acid with an alcohol solvent can include wherein said alcohol solvent is methanol.
• said process of producing acrylic acid with an alcohol solvent can include wherein said alcohol solvent is selected from ethanol and propanol.
• the process of producing acrylic acid with an alcohol solvent can include wherein said alcohol solvent is butanol.
• the process of producing acrylic acid with an alcohol solvent can include, wherein said alcohol solvent is hexanol.
• the process of producing acrylic acid can include wherein said organic solvent is selected from the group consisting of aldehydes, ketones and ethers. In another embodiment the process of producing acrylic acid can further comprise wherein about 90% of 3-HP is recovered from said concentrated fermentation broth after step (b). In another embodiment the process of producing acrylic acid can comprise wherein the catalyst is bentonite clay. In another embodiment the process of producing acrylic acid can comprise wherein the inert surface area comprises glass beads. In another embodiment the process of producing acrylic acid can comprise wherein the dehydration reaction temperature is 250°C, 275°C, or 300°C. In another embodiment the process of producing acrylic acid can include wherein the dehydration reaction pressure is 60 psi to 80 psi.
• the process of producing acrylic acid can comprise wherein a polymerization inhibitor is added to the aqueous 3-HP solution prior to vaporization.
• the process of producing acrylic acid can include wherein a polymerization inhibitor monomethyl ether of hydro quinone is added to the aqueous 3-HP solution prior to vaporization.
• the process of producing acrylic acid can include wherein a polymerization inhibitor monomethyl ether of hydro quinone is added to the aqueous 3-HP solution prior to vaporization at approximately 200 ppm or approximately 250-300 g/L 3-HP in water.
• the process of producing acrylic acid can further comprise wherein the vaporization occurs concurrently with contacting the dehydration catalyst.
• the process of producing acrylic acid can comprise wherein the aqueous 3-HP solution is a dilute 3-HP solution. In another embodiment the process of producing acrylic acid can include wherein the aqueous 3-HP solution is a dilute 3-HP solution and is present at 30% or 35% 3-HP by weight. In another embodiment the process of producing acrylic acid can further comprise wherein undesirable amounts of other forms of 3-HP, such as dimers and esters, are not formed.
• the present invention also provides a process of producing an acrylic acid produced by the steps of: (a) providing a fermentation broth comprising 3-HP, or salt thereof; (b) removing a substantial amount of water from said fermentation broth to give a concentrated fermentation broth; (c) extracting said 3-HP from said concentrated fermentation broth with an organic solvent; (d) distilling said 3-HP to give an aqueous high purity 3-HP; (e) vaporizing said high purity 3-HP to produce a 3-HP/water vapor; and (f) contacting the 3- HP/water vapor with a catalyst or inert surface area in a fixed bed reactor, thereby converting the 3-HP to acrylic acid.
• the present invention provides for a process of producing a 3-HP -based product, comprising the steps of (a) producing 3-HP according to the process of claim 1 ; and (b) converting said 3-HP into a 3-HP -based product.
• the 3-HP -based product can be diaper, a feminine hygiene product, an adult incontinence product, a paint, a coating, an ink, and a thickening agent.
• the present invention also provides a system, comprising: (a) a fermenter; (b) an evaporator; (c) a centrifuge; (d) an extractor; (e) a reactive distillation apparatus; (f) a vaporizor; and (g) a fixed bed reactor.
• the system can comprise wherein said evaporator is upstream of said extractor.
• the system can further comprise, wherein water is removed by said evaporator.
• said fermenter comprises a fermentation broth having a 3-HP concentration of at least 10 g/L.
• said centrifuge comprises a liquid phase having a 3-HP concentration of at least 10 g/L.
• the present invention also provides a process of making acrylic acid from 3-HP purified from a fermentation broth, comprising the steps of (a) removing a substantial amount of water from said fermentation broth to give a concentrated fermentation broth; and (b) extracting said 3-HP from said concentrated fermentation broth with an organic solvent; (c) vaporizing said extracted 3-HP to produce a 3-HP/water vapor; and (d) contacting the 3- HP/water vapor with a catalyst or inert surface area in a fixed bed reactor, thereby converting the extracted 3-HP to acrylic acid.
• FIG. 1 illustrates a system and process of obtaining high purity 3-HP and production of 3-HP ester, 3-HP amide and acrylamide embodying principles of the present invention.
• FIG. 2 illustrates an embodiment of a system for producing acrylamide embodying principles of the present invention.
• a system can include, but is not limited to: a fermenter 201, a holding tank 202, three centrifuges 203, 206 and 209, a wiped film evaporator 205, an acid tank 208, a counter current extractor 211, an alcohol tank 212, a reactive distillation apparatus 214, a 3-HP ester tank 215, an ammonia tank 216, an acrylamide reactor 217 and an acrylamide tank 218.
• FIG. 3 illustrates an embodiment of a system for producing acrylic acid by dehydration from high purity 3-HP
• FIG. 4A illustrates an embodiment of a chemical process for 3-HP dehydration.
• FIG. 4B illustrates how average conversion %, average yield % is determined for dehydration of 3HP to acrylic acid.
• FIG. 5 illustrates the ranges of temperatures during 3-HP dehydration for reactor inlet temperature, reactor outlet temperature, furnace set-points used over a 7 hour period.
• FIG. 6 illustrates the percent conversion and yield performance of a system for the conversion into acrylic acid.
• FIG. 7 illustrates the mass production performance for Acrylic Acid (AA) and 3-HP of a system for the conversion into acrylic acid.
• FIG. 8 illustrates the mass balance performance for Acrylic Acid (AA) and 3-HP of a system for the conversion into acrylic acid.
• the present disclosure provides processes for the purification of 3-HP from a crude fermentation broth and downstream processes to produce other chemical products, for example, acrylamide, 1, 3 -propanediol, acrylic acid, 3-HP esters, 3-HP amide, and acrylic esters.
• a variety of industrial and consumer products can be further derived from chemical products produced from 3-HP.
• a process to produce high purity 3-hydroxypropionic acid (3-HP) from a fermentation broth comprising (a) removing a substantial amount of water from the fermentation broth to give a concentrated fermentation broth; and (b) extracting the concentrated fermentation broth with an organic solvent.
• the process of the present disclosure is useful for recovery of 3-HP from a microbial fermentation broth.
• the process of the present disclosure is particularly useful for recovery of 3-HP produced via a microbial fermentation process in which 3-HP needs to be recovered or purified at some point in the fermentation or manufacturing process.
• Fermentation broth used in the present disclosure is not limited to any particular organism, pathways, carbon source, composition, nature of impurities, the amount of whole cells and initial 3-HP concentration after fermentation. Fermentation broth used in the present disclosure may contain a substantial amount of whole cells or may be substantially whole-cell free. If desired, a substantial amount of whole cells can be removed with a centrifuge.
• Methods of removing water are well-known and include, for example, distillation and evaporation.
• a variety of equipment for the above mentioned methods is commercially available.
• Distillation can be conducted at certain temperature and/or pressure. The choice of a particular temperature and/or pressure may depend on factors, such as, the size of distillation equipment, the volume of fermentation broth and the initial concentration of 3- HP.
• the temperature may be higher than 30 °C.
• the temperature is in a range of 60 -150 °C.
• the evaporation is performed at atmospheric or under reduced pressure.
• the pressure is a range of 20-60 mbar.
• Water can also be removed by using azeotropic distillation.
• solvent for azeotropic distillation include benzene, toluene, pentane, cyclohexane, hexane, heptane, isooctane, acetone, alcohols, and diethyl ether.
• azeotropic distillation the distillation of a water-containing distillate removes water.
• a concentrated fermentation broth is obtained.
• the concentrated fermentation broth may still contain water, which can be used directly in the extraction step (step b).
• 3-HP contains a carboxylic acid group.
• Carboxylic acid usually exists in two forms in aqueous media, acid form (COOH) and ionized form (COO ). The equilibrium between the two forms is usually dictated by pH of the aqueous media.
• the acid form usually has higher solubility in an organic solvent than its ionized form.
• acidification of the concentrated fermentation broth may be needed to enhance the extraction efficiency in step b.
• the acid used for adjusting pH may be a mineral acid.
• Non-limiting examples of mineral acid include sulfuric acid, hydrochloric acid, polyphosphoric acid, phosphoric acid and hydrobromic acid.
• suitable organic solvents include, for example, alcohols, ketones, aldehydes and ethers.
• suitable organic solvents include, for example, alcohols, ketones, aldehydes and ethers.
• alcohols are C1-C12 alcohols, for example, methanol, ethanol, n-propanol, isopropanol, n-butanol, iso-butanol, tert-butanol, 2-hexanol, n-octanol and their isomers.
• aldehydes are methyl aldehyde, ethyl aldehyde, propyl aldehyde, butyl aldehyde and their isomers.
• Non- limiting examples of ketones are acetone and methyl ethyl ketone.
• Non- limiting examples of ethers are tetrahydrofuran, 1,2- dimethoxyethane and 2-methyltetrahydrofuran.
• water-soluble alcohols such as, methanol and ethanol
• methanol and ethanol are suitable solvents for extracting 3-HP.
• the use of methanol and ethanol as solvent is limited by their miscible nature with water. Even in cases phase separation does occur, the extraction efficiency is usually low because the aqueous layer contains a substantial amount of methanol or ethanol.
• the organic solvent used in the present invention has a boiling point lower than that of 3-HP or 3-HP salt in the fermentation broth. In some further embodiments, the organic solvent used in the present invention has a boiling point of less than 170 °C at 1 atmosphere pressure. In some further embodiments, the organic solvent has a boiling point equal to or lower than that of hexanol. In various embodiments, during the distillation process to purify 3-HP or an ester or amide thereof, the organic solvent is distilled and collected prior to the collection of 3-HP, or its ester or amide thereof.
• the present invention also provides a process to produce 3-HP ester from a fermentation broth, comprising the steps of (a) removing a substantial amount of water from the fermentation broth to give a concentrated fermentation broth; (b) extracting the 3-HP from the concentrated fermentation broth with an alcohol solvent; and (c) refluxing or distilling the 3-HP containing extract to generate the 3-HP ester.
• the process of producing the 3-HP ester may require acid in step c.
• the acid may come from different steps of the process.
• the concentrated fermentation broth may be acidified prior to extraction of step b to give a concentrated fermentation broth which is acidic.
• the 3-HP extract from step b may contain enough acid for the esterification reaction in step c. In cases extra acid is needed, acid can be added prior or during step c.
• the acid used for acidification of the fermentation broth and the acidification in step c may be the same or different.
• the acid is selected from the group consisting of a nitrogen, halogen, sulfur and phosphorous acid.
• Non-limiting examples of acid include sulfuric acid, hydrochloric acid, phosphoric acid, polyphosphoric acid, hydrobromic acid and mixture thereof.
• the present invention also provides a process of producing 3-HP amide from a fermentation broth, comprising (a) removing a substantial amount of water from the fermentation broth to give a concentrated fermentation broth; (b) extracting the 3-HP from the concentrated fermentation broth with an alcohol solvent; and (c) converting the 3-HP to 3-HP amide.
• the conversion of 3-HP to 3-HP amide generally includes the steps of ester formation and amidation.
• synthesis of 3-HP amide may be accomplished by refluxing the 3-HP containing extract to generate a 3-HP ester; and carrying out an amidation reaction with, for example, ammonia gas or an ammonium ion, to generate the 3-HP amide.
• the present invention also provides a process of producing acrylamide from a fermentation broth, comprising the steps of (a) removing a substantial amount of water from the fermentation broth to give a concentrated fermentation broth; (b) extracting the 3-HP from the concentrated fermentation broth with an alcohol solvent; and (c) converting the 3- HP to acrylamide.
• the conversion of 3-HP to acrylamide generally includes steps of amide formation and dehydration.
• the amide formation step may require activation of the carboxylic acid group and amidation. These steps may be carried out in any order. For example, synthesis of acrylamide may be accomplished by refluxing the 3-HP containing extract to generate a 3-HP ester; carrying out an amidation reaction to generate the 3-HP amide; and dehydration to give acrylamide.
• the present invention also provides a process of producing acrylic acid from 3-HP fermentation broth, comprising the steps of (a) removing a substantial amount of water from the fermentation broth to give a concentrated fermentation broth; (b) optionally extracting the 3-HP from the concentrated fermentation broth with a solvent, such as an alcohol solvent; (c) vaporizing the aqueous 3-HP solution; and (d) converting the 3-HP to acrylic acid.
• the conversion of 3-HP to acrylic acid generally includes the step of dehydration of 3-HP.
• 3-HP can be dehydrated to acrylic acid in high conversion and yield in a fixed bed reactor using a catalyst such as bentonite clay (F-24 from BASF) or an inert surface area such as glass beads.
• the dehydration reaction with a catalyst can be run at around 250°C, and may include the use of an inhibitor in the feed solution.
• Monomethyl ether of hydroquinone (MEHQ) may be used as the inhibitor, and preferably may be present at approximately 200 ppm or approximately 250-300 g/L 3 -HP in water.
• Dehydration converts a carbon-carbon single bond to a carbon-carbon double bond and produces a water molecule.
• the dehydration may take place in the presence of a suitable homogeneous or heterogeneous catalyst.
• Suitable dehydration catalysts include acids, bases and oxides.
• acids are H 2 SO 4 , HC1, titanic acids, metal oxide hydrates, metal sulfates (MSO 4 ,.
• bases are NaOH, ammonia,
• Non-limiting examples of oxides are Ti0 2 , Zr0 2 , A1 2 0 3 , Si0 2 , Zn0 2 , Sn0 2 , W0 3 , Mn0 2 , Fe 2 0 3 , V 2 0 5 .
• FIG. 1 depicts one scheme illustrating the isolation of high purity 3-HP from a fermentation broth and the downstream production of 3-HP ester and acrylamide embodying the principles of the present invention. It is understood that the order of steps in FIG. 1 is illustrative and may be altered based on a variety of factors, for example, the scale of the purification, the impurity in the fermentation broth, the solvent, and the equipment used for fermentation and purification. In addition, any of the steps may be repeated or some of the steps may be eliminated. The process described in FIG. 1 should not limit the scope of the present invention.
• a whole fermentation broth from fermentation may be transferred from a fermenter to separation equipment and subjected to a separation step 101.
• the concentration of 3-HP in the fermentation broth may be at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, or 30 g /L.
• Step 101 may allow the separation of a substantial amount of whole cells from the whole fermentation broth to give a clarified fermentation broth.
• the amount of whole cell removed from the whole fermentation broth may be at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of the initial amount of whole cells.
• a variety of techniques may be employed for the separation.
• the whole fermentation broth may be left undisturbed for a selected period of time to achieve the desired separation.
• the selected period of time may be about 2 hrs, about 4 hrs, about 6 hrs, about 8 hrs, about 12 hrs, about 18 hrs, about 24 hrs, about 36 hrs, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, or about 1 week.
• the whole fermentation broth is subjected to centrifugal force to remove whole cells. The speed and the length of the centrifugation can be controlled.
• the centrifugation may be run at a speed of at least 250 G, at least 500 G, at least 1,000 G, at least 1,500 G, at least 2,000 G, at least 2,500 G, at least 3,000G, at least 3,500 G, at least 4,000 G, at least 4,500 G, at least 5,000G, at least 5,500 G, at least 6,000G, at least 6,500 G, at least 7,000 G, at least 8, 000 G, at least 9,000 G, or at least 10,000 G.
• the centrifuge may be run at a speed of 250-7000 G.
• the centrifugation may last at least 5 minutes, at least 10 minutes, at least 15 minutes, at least 20 minutes, at least 25 minutes, at least 30 minutes, at least 35 minutes, at least 40 minutes, at least 50 minutes, at least 60 minutes, at least 80 minutes, at least 100 minutes, at least 120 minutes, at least 140 minutes, at least 160 minutes, at least 180 minutes, at least 200 minutes, at least 250 minutes, at least 300 minutes, at least minutes 400 minutes, or at least 500 minutes. In some cases, the centrifugation may last 5-500 minutes.
• the centrifugation step may keep cells intact, which may make the addition of flocculating agents to achieve clarity unnecessary.
• flocculating agents may be added. Flocculating agents reduce zeta potential of charged particles and thus facilitate the aggregation (floe formation) of the particles.
• Non- limiting examples of flocculating agents may include, but are not limited to, neutral electrolytes such as KC1, NaCl, calcium salts, alum, sulfate, citrates, and phosphates salts.
• the amount of flocculating agent added to the whole broth 101 may be about 0.0001 g/L, about 0.001 g/L, about 0.01 g/L, about 0.05 g/L, about 0.1 g/L, about 0.2 g/L, about 0.3 g/L, about 0.4 g/L, about 0.5 g/L, about 0.6 g/L, about 0.7 g/L, about 0.8 g/L, about 0.9 g/L, about 1 g/L, about 2 g/L, about 3 g/L, about 4 g/L, about 5 g/L, about 6 g/L, about 7 g/L, or about 10 g/L.
• the amount of flocculating agent added to the whole broth 101 may be 0.01-10 g/L.
• the amount of flocculating agent may depend on the types of the agent used.
• a clarified fermentation broth is generated.
• a substantial amount of water in the clarified fermentation broth is removed in step 102.
• a variety of techniques well known in the art may be used to remove water, for example, evaporation, boiling and distillation.
• the amount of water being removed may be at least at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of the initial amount.
• Some water maybe chemically bound and may not be easily removed under evaporative conditions.
• the water is removed by evaporation. It is well-known in the art that evaporation of water can be conducted in a variety of ways, for example, by reducing the pressure and/or heating the solution.
• the pressure is in a range of an ambient atmospheric pressure and about 0.1 mbar. In some embodiments, the pressure is in a range of 20-80 mbar. In some other embodiments, the pressure is an ambient atmospheric pressure.
• the temperature for water removal may be in a range of 25 0 C and 150 0 C, depending upon the pressure, the scale of the reaction and the equipment used for the distillation. In certain other embodiments, the evaporation of water may be achieved by mechanical recompression methods.
• Mechanical recompression evaporator is commercially available, for example, from Swenson Technology, Inc.
• the mechanical recompression methods may be more economical to remove water than evaporation.
• a high concentration of 3-HP would be desirable.
• the concentration fold would depend on the titer of the fermentation broth.
• broth of 50 g/L 3-HP needs to be concentrated about 15 fold.
• a fermentation broth of 100 g/L 3- HP would only need to be concentrated 7.5 fold.
• the distilled water can be re-used in the fermentation process.
• a concentrated fermentation broth is obtained.
• the concentration of 3-HP in the concentrated fermentation broth may be at least 50 g/L, or at least 60 g/L, 70 g/L, 80 g/L, 90 g/L, 100 g/L, or 110 g/L.
• the concentration of 3-HP in the concentrated fermentation broth may be in a range of 50-200 g/L.
• 3-HP may remain a liquid in the mixture, and impurities, such as salts and proteins, may become insoluble.
• the impurities may be separated in step 103 by taking advantage of their immiscible nature with 3-HP.
• Step 103 may be carried out during and/or after removing water.
• the impurities are separated during concentration using a scraped drum evaporator.
• the impurities are separated after the concentration using centrifugation or filtration. If desired, the solids can be washed with an organic solvent to improve recovery of 3-HP.
• a clarified concentrated fermentation broth is obtained. There may be some residual impurities in the clarified concentrated fermentation broth.
• the amount of impurities may be at least at least 1.0%, at least 1.5%, at least 2.0%, at least 2.5%, at least 3.0%, at least 3.5%, at least 4.0%, at least 4.5%, at least 5.0%, at least 5.5%, at least 6.0%, at least 6.5%, at least 7.0%, at least 7.5%, at least 8.0%, at least 8.5%, at least 9.0%, at least 9.5%, at least 10.0%, at least 11.0%, at least 12.0%, at least 13.0%, at least 14.0%, or at least 15.0% of the initial amount of impurities.
• the clarified concentrated fermentation broth may be neutral or acidic.
• the pH may be in a range of 3.5-4.0, 4.0-4.5, 4.5-5.0, 5.0-5.5, 5.5-6.0, 6.0-6.5, 6.5-7.0. Since 3-HP is a carboxylic acid, an acidification step 104 may be needed. Acidification of the clarified concentrated fermentation broth will shift 3-HP to the acid form, increasing solubility of 3- HP in an extraction solvent.
• a variety of external acids may be used to adjust the pH.
• the acid may be an organic or an inorganic acid. Inorganic acid may include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid,
• polyphosphoric acid and mixture thereof.
• sulfuric acid is used.
• phosphoric acid is used.
• the choice of acid may dictate the resulting salts which then fall out of solution. These salts may be significant in that an equal molar ratio of salt to 3-HP and other organic acids is expected.
• an acidic concentrated fermentation broth is obtained.
• the pH of the broth may be in a range of below 0, 0-1, 1.0-1.5, 1.5-2.0, 2.0-2.5, 2.5-3.0, 3.0-3.5, 3.5-4.0, 4.0-4.5, 4.5-5.0, 5.0 to 5.5.
• a salt may be precipitated out of the broth.
• the salt is an ammonium salt of the chosen inorganic acid.
• the salt and the liquid may be separated in step 105 by methods, for example, filtration.
• Salts and other solids may be formed upon acidification.
• the resulting solids can then be removed during an optional filtration step.
• a wash step of the solids may be needed due to the amount of the 3-HP remaining in the interstitial space of the solid cake.
• the amount of residual 3-HP in the solid cake may be at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, or at least 50% of total 3- HP.
• the wash may be carried out with the organic solvent used in the extraction step, such as an alcohol.
• an alcohol may be selected from C1-C12 aliphatic alcohols, for example but not limited to, methanol, ethanol, 1-propanol, 1-butanol, isopropyl alcohol, isobutyl alcohol, t-butanol, 1-octanol, 1-hexanol, 2-hexanol, and their isomers.
• a selected alcohol may be an alcohol which is miscible or immiscible with water. This is in contrast to traditional biphasic extraction techniques in which water-immiscible alcohols is highly desirable to achieve phase separation. After a single wash step, the majority of 3-HP may be recovered from the solid cake.
• the amount of 3-HP recovered may be at least 50%, at least 60%), at least 65%>, at least 70%>, at least 75%>, at least 80%>, at least 85%>, at least 86%>, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, or at least 95% of the total 3-HP in the solids cake. There may be some residual salts remaining in the 3-HP stream so obtained.
• the amount of non-3-HP salts remaining in the 3- HP wash stream may be at least 0.5%, at least 1.0%, at least 1.5%, at least 2.0%, at least 2.5%, at least 3.0%, at least 3.5%, at least 4.0%, at least 4.5%, at least 5.0%, at least 6.0%, at least 7.0%, at least 8.0%, at least 9.0%, at least 10.0%, at least 11.0%, at least 12.0%, at least 13.0%, at least 14.0%, at least 15.0%, at least 18.0%, at least 20.0%, at least 25.0%, or at least 30.0% of the total stream mass.
• the wash stream may be used in a subsequent primary extraction to reduce solvent usage.
• the washed salts may be relatively pure and may be a valuable nitrogen source for agriculture upon drying.
• the purified 3-HP extract resulting after acidification and separation of the solid cake may be extracted into an organic solvent such as an alcohol.
• organic solvent such as an alcohol.
• Other solvents may be employed when potential ester formation is not desired.
• An alcohol solvent may be selected from C1-C12 aliphatic alcohols, for example but not limited to, methanol, ethanol, 1-propanol, 1-butanol, isopropyl alcohol, isobutyl alcohol, t-butanol, 1-octanol, 1-hexanol, and their isomers.
• a selected alcohol may be an alcohol which is miscible or immiscible with water.
• the amount of alcohols used should be enough to achieve desirable extraction efficiency. On the other hand, to minimize cost and environmental impact, it is desirable to use as a small amount as possible. Optimization may be required to achieve a right balance.
• about 5 mol equivalents of an alcohol solvent based on the amount of 3-HP may be used. In some further embodiments, less than 2 mol equivalents of an alcohol based on the amount of 3-HP may be used. In a particular embodiment, about 1 mol equivalent of an alcohol based on the amount of 3-HP may be used.
• the amount of alcohol solvent used may also be calculated based on the volume of purified 3-HP.
• a 3X volume of alcohol may be used.
• the extraction may be carried out in single stage or it may be carried out in multiple stages to improve extraction efficiency.
• the number of stages could depend on the type of extractor being used. For example, a Karr column or a Scheibel column may be used for extraction.
• a single stage extraction may be used.
• two separate stages may be used.
• three separate stages may be used.
• the extraction efficiency may depend on the nature and/or the amount of alcohol solvent used and/or the number of stages used for the extraction.
• the efficiency may be at least 50%, at least 60%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%o, at least 97%, or at least 98%>.
• the efficiency may be optimized and improved using a multi-stage counter current extractor or other staged type separation systems.
• the heavy phase which results from the removal of 3-HP and other organic acids, is a combination of sugars and salts. It is insoluble in alcohols and may contain some 3-HP.
• the amount of 3- HP in the heavy phase may be about 0.5%>, about 1%, about 2%, about 3%, about 4%, about 5%, about 6%), about 7%, about 8%, about 9%, or about 10%.
• this side stream may be high in carbon and may be valuable for recycle or as a sugar source.
• the 3-HP extract may contain between 200 - 300 g/L 3-HP along with other organic acids. This range may change based on many factors including final titer in fermentation. Because water solubility in an alcohol or other organic solvent is dependent on the carbon chain length various degrees of water and associated acid may result with the choice of alcohol or other organic solvent.
• 3-HP extract at this point may be purified.
• 3-HP may be purified by distillation.
• 3-HP may be purified by back-extracting into water.
• 3- HP may be precipitated as a salt by adjusting pH upwards to the salt form of the acid.
• Crystals can be obtained by the following technique/s: concentration by solvent evaporation, cooling, or the addition of a forcing solvent.
• the 3-HP extract may be transferred to an esterification reactor in step 106 and carry out an esterification reaction in step 107 without further purification to produce 3-HP ester.
• Esterification is a reaction in organic chemistry in which, typically, a carboxylic acid is reacted with an alcohol to give an ester. The reaction is usually accelerated by heating and/or catalysis. Commonly employed catalysts include acids, Lewis Acids or dehydrating reagents.
• the acid may be organic and inorganic acid.
• the Lewis acid is a substance which can employ a lone pair of electrons from another molecule in completing the stable group of one of its own atoms.
• the dehydrating agent includes any reagent which can facilitate a dehydration reaction, for example but not limited to, molecular sieves of varying grade.
• the conversion of 3-HP to its ester may be at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%.
• n-butanol is used as the extraction solvent and sulfuric acid is used as the acid to adjust pH
• enough acid may be present in the alcohol extract such that no extra acid is required for the esterification reaction. Additional acid may be required to drive the esterification upon the use of longer chain alcohols under other conditions.
• the amount could be in a range of 1 mol% to 99 mol% based on the amount of 3-HP in the extract.
• n-butanol is used as the solvent and sulfuric acid is used to adjust pH of the concentrated fermentation extract
• the alcohol extract is refluxed at the boiling point of the alcohol (118°C in this case with butanol) in the presence of a water trap.
• a phase separation trap may be used to remove the water prior to the distillate returning to the reaction vessel.
• molecular sieves may be used alone or in combination with an acid to remove the water and drive the esterification reaction to completion.
• the process may be optimized using about an equal molar ratio of alcohol to 3- HP which eliminates the need for solvent recycle because the extraction solvent is used up as a reactant.
• the increased volatility of the ester can then be used to distill the ester away from other contaminants, thus yielding high purity 3-HP ester.
• the purity of 3-HP ester is higher than 90%.
• the purity of 3-HP ester is higher than 95%.
• 3-HP ester is a highly valuable intermediate for producing other products. For example, without being limiting, dehydration of 3-HP ester would lead to acrylic ester, which is an important class of monomer for producing polyacrylic polymers and co-polymers.
• 3-HP amide can be processed to 3-HP amide using ammonia gas or ammonium ions in a trans-amidation type reaction.
• Dehydration of 3-HP amide could give acrylamide (step 108), which is used in producing polyacrylamide.
• Polyacrylamide has found broad applications in water purification, oil-drilling, gel electrophoresis, papermaking, ore processing, and the manufacture of permanent press fabrics.
• microorganism includes a single microorganism as well as a plurality of microorganisms; and the like.
• fermentation broth generally refers to a mixture derived from a microbial fermentation procedure.
• the fermentation broth may be a mixture obtained from a microbial fermentation procedure without any purification or separation.
• the term "fermentation broth” generally refers to a mixture derived from a microbial fermentation procedure.
• the fermentation broth may be a mixture obtained from a microbial fermentation procedure without any purification or separation.
• the fermentation broth may be a mixture obtained from a microbial fermentation procedure without any purification or separation.
• fermentation broth may be a mixture obtained from a microbial fermentation procedure after purification or separation.
• the fermentation broth may contain whole cells or may be substantially whole-cell free.
• methods of purification or separation a fermentation broth prior to removing water include filtration, precipitation and centrifuge.
• the fermentation broth may be treated to release 3-HP from cells. The treatment may be a lysing step.
• the fermentation broth contains 3-HP.
• 3-HP A variety of microbial systems for producing 3-HP have been described in the art, for example, U.S. Application Pub. No. 2011/0125118, US Application Pub. No. 2008/0199926, and U.S. Patent No. 6,852,517, which are herein incorporated by reference for their teaching of 3-HP production pathways and methods of microbial 3-HP production. It is understood that these references and the following discussion provide exemplary examples to which the present invention can be applied. They are meant to be illustrative. As one of ordinary skill in the art can understand, the present invention can be applied to a variety of microbial systems which produce 3-HP and related compounds.
• the microbial systems may comprise a carbon source, one or more microorganism, and suitable media and culture conditions.
• the fermentation may be carried out in a bio- production reactor. After fermenting for a certain period of time, the crude cell broth obtained may be further processed to yield high purity 3-HP or downstream products.
• the carbon source may be suitable for the intended metabolic pathway.
• Suitable carbon source may include, but are not limited to, monosaccharides such as glucose and fructose, oligosaccharides such as lactose or sucrose, polysaccharides such as starch or cellulose or mixtures thereof and unpurified mixtures from renewable feedstocks such as cheese whey permeate, cornsteep liquor, sugar beet molasses, and barley malt.
• the carbon substrates may also be one-carbon substrates such as carbon dioxide, carbon monoxide, or methanol for which metabolic conversion into key biochemical intermediates has been demonstrated.
• methylotrophic organisms are also known to utilize a number of other carbon containing compounds such as methylamine, glucosamine and a variety of amino acids for metabolic activity.
• the microorganism may have one or more natural, introduced, or enhanced 3-HP bio- production pathways.
• the microorganism may comprise an endogenous 3-HP production pathway.
• the endogenous 3-HP production pathway may be enhanced to increase 3-HP production.
• the microorganism may not comprise an endogenous 3-HP production pathway.
• the pathway can be introduced through, for example, genetic engineering.
• a microorganism may be selected from bacteria, cyanobacteria, filamentous fungi, and yeasts. Since 3-HP produced during fermentation may be toxic to the microorganism used in the process, the microorganism may further comprise tolerance aspects.
• microorganisms may include, but are not limited to, any gram negative organisms, more particularly a member of the family Enterobacteriaceae, such as E. coli, or Oligotropha carboxidovorans, or Pseudomononas sp.; any gram positive microorganism, for example Bacillus subtilis, Lactobaccilus sp. or Lactococcus sp.; a yeast, for example
• suitable microbial hosts for the bio -production of 3-HP generally include, but are not limited to, members of the genera Clostridium, Zymomonas, Escherichia, Salmonella, Rhodococcus, Pseudomonas, Bacillus, Lactobacillus, Enterococcus, Alcaligenes, Klebsiella, Paenibacillus, Arthrobacter, Corynebacterium, Brevibacterium, Pichia, Candida, Hansenula and Saccharomyces. Hosts that may be particularly of interest include:
• Oligotropha carboxidovorans such as strain OM5
• Escherichia coli Alcaligenes eutrophus (Cupriavidus necator)
• Bacillus licheniformis Bacillus licheniformis
• Paenibacillus macerans Rhodococcus erythropolis
• Pseudomonas putida Lactobacillus plantarum
• Enterococcus faecium Oligotropha carboxidovorans (such as strain OM5)
• Escherichia coli Alcaligenes eutrophus (Cupriavidus necator)
• Bacillus licheniformis Bacillus licheniformis
• Paenibacillus macerans Rhodococcus erythropolis
• Pseudomonas putida Lactobacillus plantarum
• Enterococcus faecium Enterococcus faecium
• Enterococcus gallinarium Enterococcus faecalis
• Bacillus subtilis Bacillus subtilis and Saccharomyces cerevisiae.
• Patent Application Pub. No. 2011/0183391 Al . incorporated by reference for such teachings.
• genetic engineering may be used.
• one or more additives may be added to the cell culture to modulate fatty acid synthase or malonyl-CoA reductase to increase the production of 3 -HP.
• bio -production media must contain suitable minerals, salts, cofactors, buffers and other components, known to those skilled in the art, suitable for the growth of the cultures and promotion of the enzymatic pathway necessary for 3-HP production, or other products.
• Suitable growth media in the present invention are common commercially prepared media such as Luria Bertani (LB) broth, M9 minimal media, Sabouraud Dextrose (SD) broth, Yeast medium (YM) broth, yeast synthetic minimal media (Ymin), and minimal media as described herein, such as M9 minimal media.
• LB Luria Bertani
• SD Sabouraud Dextrose
• YM yeast medium
• Ymin yeast synthetic minimal media
• minimal media as described herein, such as M9 minimal media.
• Other defined or synthetic growth media may also be used, and the appropriate medium for growth of the particular
• a minimal media may be developed and used that does not comprise, or that has a low level of addition of various components, for example less than 10, 5, 2 or 1 g/L of a complex nitrogen source including but not limited to yeast extract, peptone, tryptone, soy flour, corn steep liquor, or casein.
• a complex nitrogen source including but not limited to yeast extract, peptone, tryptone, soy flour, corn steep liquor, or casein.
• These minimal medias may also have limited supplementation of vitamin mixtures including bio tin, vitamin B12 and derivatives of vitamin B12, thiamin, pantothenate and other vitamins.
• Minimal medias may also have limited simple inorganic nutrient sources containing less than 28, 17, or 2.5 mM phosphate, less than 25 or 4 mM sulfate, and less than 130 or 50mM total nitrogen.
• Bio-production media must contain suitable carbon substrates for the intended metabolic pathways.
• suitable carbon substrates may include carbon monoxide, carbon dioxide, various monomeric and oligomeric sugars, amines, and amino acids.
• Suitable H ranges for the bio -production are between pH 3.0 to pH 10.0, where pH 6.0 to pH 8.0 is a typical pH range for the initial condition. However, the actual culture conditions for a particular embodiment are not meant to be limited by these pH ranges.
• Bio-productions may be performed under aerobic, microaerobic, or anaerobic conditions, with or without agitation and with or without external heating or cooling.
• the amount of 3-HP or other product(s) produced in a bio -production media generally can be determined using a number of methods known in the art, for example, high
• HPLC performance liquid chromatography
• GC gas chromatography
• MS GC/Mass Spectroscopy
• any of the microorganisms as described and/or referred to herein may be introduced into an industrial bio -production system where the microorganisms convert a carbon source into 3-HP in a commercially viable operation.
• the bio -production system includes the introduction of such a microorganism into a bioreactor vessel, with a carbon source substrate and bio -production media suitable for growing the microorganism, and maintaining the bio- production system within a suitable temperature range (and dissolved oxygen concentration range if the reaction is aerobic or microaerobic) for a suitable time to obtain a desired conversion of a portion of the substrate molecules to 3-HP.
• the fermentation process may be monitored by measuring the concentration of 3-HP in crude fermentation broth.
• Industrial bio -production systems and their operation are well-known to those skilled in the arts of chemical engineering and bioprocess engineering.
• Bio-productions may be performed under aerobic, microaerobic, or anaerobic conditions, with or without agitation.
• the operation of cultures and populations of microorganisms to achieve aerobic, microaerobic and anaerobic conditions are known in the art, and dissolved oxygen levels of a liquid culture comprising a nutrient media and such microorganism populations may be monitored to maintain or confirm a desired aerobic, microaerobic or anaerobic condition.
• a variety of separation techniques may be applied for the purification of 3-HP from crude cell broth including, but are not limited to, centrifugation, evaporation, boiling, distillation, filtration, extraction, washing, crystallization, and precipitation.
• the techniques cited herein are meant to be illustrative and are well known in the art. Each technique may be used alone or in any combination or may be used once or multiple times. Instruments or apparatus for carrying out the purification techniques mentioned herein are well known in the art and may be commercially available in different shapes and sizes. Without being limiting, some aspects of selected techniques are described herein.
• Centriiugation involves the use of a centrifugal force for the sedimentation of mixtures, typically with a centrifuge. When there are multiple components in the mixture, controlling the rate and length of the centriiugation may lead to successive separation of different components.
• the rate of centriiugation may be at least 250 G, at least 500 G, at least 1 ,000 G, at least 1 ,500 G, at least 2,000 G, at least 2,500 G, at least 3,000 G, at least 3, at least 500 G, at least 4,000 G, at least 4,500 G, at least 5,000 G, at least 5,500 G, at least 6,000 G, at least 6,500 G, at least 7,000 G, at least 8,000 G, at least 9,000 G, at least 10,000 G, at least 12,000 G, at least 14,000 G, at least 16, 000 G, at least 20,000 G, at least 30,000 G, at least 40,000 G, at least 50,000 G, or at least 100,000 G.
• the length of centrifugation may be at least 1 minute, at least 2 minutes, at least 3 minutes, at least 4 minutes, at least 5 minutes, at least 6 minutes, at least 7 minutes, at least 8 minutes, at least 9 minutes, at least 10 minutes, at least 12 minutes, at least 14 minutes, at least 15 minutes, at least 18 minutes, at least 20 minutes, at least 25 minutes, at least 30 minutes, at least 35 minutes, at least 40 minutes, at least 60 minutes, at least 80 minutes, at least 100 minutes, at least 200 minutes, at least 300 minutes, at least 400 minutes, at least 500 minutes, at least 600 minutes, at least 800 minutes, at least 1 ,000 minutes, at least 2,000 minutes, at least 3,000 minutes, at least 4,000 minutes, 5,000 minutes, at least 6,000 minutes, or at least 7,000 minutes. Centrifuges are commercially available and well known in the art.
• Evaporation is the process of vaporizing a liquid, typically from the surface.
• Evaporation may be accelerated in a variety of ways to improve the rate of evaporation and/or energy efficiency including, but are not limited to, reducing pressure surrounding the liquid and/or heating the liquid.
• the pressure and/or the temperature chosen for the evaporation may depend on a variety of factors, such as the scale, the solvent, and the equipment for the purification.
• An ambient atmospheric pressure may be used.
• a pressure lower than an ambient atmospheric pressure may be used.
• the pressure may be about 0.1 mbar, about 0.5 mbar, about 1 mbar, about 2 mbar, about 3 mbar, about 4 mbar, about 5 mbar, about 6 mbar, about 7 mbar, about 8 mbar, about 9 mbar, about 10 mbar, about 12 mbar, about 15 mbar, about 18 mbar, about 20 mbar, about 25 mbar, about 30 mbar, about 35 mbar, about 40 mbar, about 45 mbar, about 50 mbar, about 55 mbar, about 60 mbar, about 65 mbar, about 70 mbar, about 75 mbar, about 80 mbar, about 90 mbar, about 100 mbar, about 120 mbar, about 150 mbar, about 200 mbar, or 300 mbar.
• the pressure may be in a range of 0.1-300 mbar.
• the temperature may be about 25 °C, about 28 °C, about 30 °C, about 35 °C, about 40 °C, about 45 °C, about 50 °C, about 55 °C, about 60 °C, about 65 °C, about 70 °C, about 75 °C, about 80 °C, about 85 °C, about 90 °C, about 95 °C, about 100 °C, about 105 °C, about 110 °C, about 115 °C, about 120 °C, about 125 °C, about 130 °C, about 135 °C, or about 150 0 C.
• the temperature may be in a range of 25- 180 °C.
• Mechanical recompression techniques may also be used for the evaporation.
• a mechanical recompression evaporator functions by compressing a vapor to a relatively high pressure so it can be condensed in an evaporator heat exchanger. The compression can be achieved with a positive-displacement, centrifugal, or axial flow compressor.
• the mechanical recompression may comprise single-effect recompression, multiple-effect recompression, single-stage recompression, multiple-stage recompression, and any combination thereof.
• Distillation is the process of heating a liquid until it boils, and then condensing and collecting the hot vapor. Similar to evaporation, distillation can be carried out under reduced pressure and/or heating. Reducing the pressure around the liquid may reduce the boiling point of the liquid, thus facilitating distillation.
• the pressure may be an ambient atmospheric pressure or lower.
• the pressure may be about 0.1 mbar, about 0.5 mbar, about 1 mbar, about 2 mbar, about 3 mbar, about 4 mbar, about 5 mbar, about 6 mbar, about 7 mbar, about 8 mbar, about 9 mbar, about 10 mbar, about 12 mbar, about 15 mbar, about 18 mbar, about 20 mbar, about 25 mbar, about 30 mbar, about 35 mbar, about 40 mbar, about 45 mbar, about 50 mbar, about 55 mbar, about 60 mbar, about 65 mbar, about 70 mbar, about 75 mbar, about 80 mbar, about 90 mbar, about 100 mbar, about 120 mbar, about 150 mbar, about 200 mbar, or 300 mbar.
• the pressure may be in a range of 0.1 - 1 ,000 mbar.
• the temperature may be about 25 °C, about 28 °C, about 30 °C, about 35 °C, about 40 °C, about 45 °C, about 50 °C, about 55 °C, about 60 °C, about 65 °C, about 70 °C, about 75 °C, about 80 °C, about 85 °C, about 90 °C, about 95 °C, about 100 °C, about 105 °C, about 110 °C, about 115 °C, about 120 °C, about 125 °C, about 130 °C, about 135 °C, or about 150 °C.
• the temperature may be in a range of 25- 180 °C.
• Filtration is a technique used to separate solids from liquids by passing the mixture through a media through which mainly the liquids may pass. Filtration can be aided with or without additional solvent. After filtration, the solids may still contain some residual liquids. In some embodiments, the solids may contain by volume a ratio of about 10%, about 11%, about 12%), about 15%, about 20%>, about 25%, about 30%>, about 35%, about 40%>, about 50%), about 60%), of the total volume of the liquids. The solids may be washed with a solvent to reduce the amount of residual liquids in the solids.
• the amount of residual liquids may be reduced by at least 20%>, at least 30%>, at least 40%>, at least 50%>, at least 60%, at least 70%, at least 80%, or at least 90%.
• the combined recovered 3-HP may be at least 70%, at least 80%, or at least 90% of the total amount.
• 3- hydroxypropionic acid 3-HP
• This organic acid, 3-HP may be converted to various other products having industrial uses including, but are not limited to, acrylamide, acrylic acid, esters of acrylic acid, 1,3-propanediol, and other chemicals, collectively referred to as "downstream chemical products.” In some instances the conversion is associated with the separation and/or purification steps. These downstream chemical products are useful for producing a variety of consumer products which will be described in detail herein.
• the methods of the present invention include steps to produce downstream products of 3-HP.
• 3-HP offers much potential in a variety of chemical conversions to commercially important intermediates, industrial end products, and consumer products.
• 3-HP may be converted to acrylic acid, acrylates (e.g., acrylic acid salts and esters), 1,3-propanediol, malonic acid, ethyl-3 -hydro xypropionate, ethyl ethoxy propionate, propio lactone, acrylamide, or acrylonitrile.
• 3-HP may be converted to acrylic acid through a process including the steps of: (1) vaporizing an aqueous 3-HP solution; and (2) contacting the 3-HP and water vapor with a dehydration catalyst or inert surface area, thereby converting the 3-HP to acrylic acid without the formation of an undesired level of polymerization of acrylic acid.
• the dehydration step may be done in a fixed bed reactor.
• an aqueous 3-HP solution may be used as the feedstock.
• This solution may be converted to a gaseous mixture prior to or concurrent with contacting with a dehydration catalyst in a fixed bed reactor.
• lower concentrations of 3-HP in water i.e., a dilute 3-HP solution
• the solution is about 30% or about 35% 3-HP by weight.
• undesirable amounts of other forms of 3-HP, such as dimers and esters, are not formed during the process.
• bentonite clay e.g., F-24 from BASF
• the dehydration reaction can be run at around 250°C, 275°C or 300°C, and at 60 - 80 psi.
• the 3-HP is not preheated, but is heated using a heat transfer block inside the reactor to achieve better temperature control.
• the fixed bed reactor includes inert surface area to facilitate dehydration of 3-HP to acrylic acid.
• the inert surface area may comprise glass beads packed into the fixed bed reactor.
• dehydration reaction can be run at around 275 °C or 300°C.
• the flow rate of the solution within the reactor is important and is preferably closely regulated. Too low a residence time in the reactor can prevent the dehydration reaction from occurring, while too high a flow rate can result in polymer formation. Preferably the flow rate is maintained at about 1 ml/min per 1 ⁇ 4 inch diameter of the feed line.
• a polymerization inhibitor may be added to the aqueous solution of 3-HP, and/or added into the 3-HP/water vapor.
• a non-limiting example of a polymerization inhibitor is hydroquinone monomethyl ether (MEHQ), which preferably may be present at approximately 200 ppm or approximately 250-300 g/L 3-HP in water in the vapor feed.
• 3-HP may be oligomerized or polymerized to form poly(3- hydroxypropionate) homopolymers, or co-polymerized with one or more other monomers to form various co-polymers. Because 3-HP has only a single stereoisomer, polymerization of 3-HP is not complicated by the stereo-specificity of monomers during chain growth. This is in contrast to (S)-2-Hydroxypropanoic acid (also known as lactic acid), which has two (D, L) stereoisomers that must be considered during its polymerizations.
• 3-HP can be converted into derivatives starting (i) substantially as the protonated form of 3-hydroxypropionic acid; (ii) substantially as the deprotonated form, 3-hydroxypropionate; or (iii) as mixtures of the protonated and deprotonated forms.
• the fraction of 3 -HP present as the acid versus the salt will depend on the pH, the presence of other ionic species in solution, temperature (which changes the equilibrium constant relating the acid and salt forms), and to some extent pressure.
• Many chemical conversions may be carried out from either of the 3-HP forms, and overall process economics will typically dictate the form of 3-HP for downstream conversion.
• Acrylic acid obtained from 3-HP made by the present invention may be further converted to various polymers.
• the free-radical polymerization of acrylic acid takes place by polymerization methods known to the skilled worker and can be carried out either in an emulsion or suspension in aqueous solution or another solvent.
• Initiators such as but not limited to organic peroxides, often are added to aid in the polymerization.
• organic peroxides that may be used as initiators are diacyls, peroxydicarbonates, monoperoxycarbonates, peroxyketals, peroxyesters, dialkyls, and hydroperoxides.
• azo initiators Another class of initiators is azo initiators, which may be used for acrylate polyermization as well as co -polymerization with other monomers.
• U.S. Patent Nos. 5,470,928; 5,510,307; 6,709,919; and 7,678,869 teach various approaches to polymerization using a number of initiators, including organic peroxides, AZO compounds, and other chemical types, and are
• co-monomers such as crosslinkers
• co-monomers such as crosslinkers
• the free-radical polymerization of the acrylic acid obtained from dehydration of 3-HP, as produced herein, in at least partly neutralized form and in the presence of crosslinkers is practiced in certain embodiments.
• This polymerization may result in hydrogels which can then be comminuted, ground and, where appropriate, surface-modified, by known techniques.
• Superabsorbent polymers are primarily used as absorbents for water and aqueous solutions for diapers, adult incontinence products, feminine hygiene products, and similar consumer products. In such consumer products, superabsorbent materials can replace traditional absorbent materials such as cloth, cotton, paper wadding, and cellulose fiber. Superabsorbent polymers absorb, and retain under a slight mechanical pressure, up to 25 times or more their weight in liquid.
• Superabsorbent polymer particles can be surface-modified to produce a shell structure with the shell being more highly crosslinked. This technique improves the balance of absorption, absorption under load, and resistance to gel-blocking. It is recognized that superabsorbent polymers have uses in fields other than consumer products, including agriculture, horticulture, and medicine.
• Superabsorbent polymers are prepared from acrylic acid (such as acrylic acid derived from 3-HP provided herein) and a crosslinker, by solution or suspension
• Exemplary methods include U.S. Patent Nos. 5,145,906; 5,350,799;
• a diaper, a feminine hygiene product, and an adult incontinence product are made with superabsorbent polymer that itself is made substantially from acrylic acid converted from 3-HP made in accordance with the present invention.
• Diapers and other personal hygiene products may be produced that incorporate superabsorbent polymer made from acrylic acid made from 3-HP which is bio-produced by the teachings of the present application.
• the following provides general guidance for making a diaper that incorporates such superabsorbent polymer.
• the superabsorbent polymer first is prepared into an absorbent pad that may be vacuum formed, and in which other materials, such as a fibrous material (e.g., wood pulp) are added.
• the absorbent pad then is assembled with sheet(s) of fabric, generally a nonwoven fabric (e.g., made from one or more of nylon, polyester, polyethylene, and polypropylene plastics) to form diapers.
• a nonwoven fabric e.g., made from one or more of nylon, polyester, polyethylene, and polypropylene plastics
• a conveyer belt above a conveyer belt multiple pressurized nozzles spray superabsorbent polymer particles (such as about 400 micron size or larger), fibrous material, and/or a combination of these onto the conveyer belt at designated spaces/intervals.
• the conveyor belt is perforated and under vacuum from below, so that the sprayed on materials are pulled toward the belt surface to form a flat pad.
• fibrous material is applied first on the belt, followed by a mixture of fibrous material and the superabsorbent polymer particles, followed by fibrous material, so that the superabsorbent polymer is concentrated in the middle of the pad.
• a leveling roller may be used toward the end of the belt path to yield pads of uniform thickness.
• Each pad thereafter may be further processed, such as to cut it to a proper shape for the diaper, or the pad may be in the form of a long roll sufficient for multiple diapers. Thereafter, the pad is sandwiched between a top sheet and a bottom sheet of fabric (one generally being liquid pervious, the other liquid impervious), such as on a conveyor belt, and these are attached together such as by gluing, heating or ultrasonic welding, and cut into diaper-sized units (if not previously so cut). Additional features may be provided, such as elastic components, strips of tape, etc., for fit and ease of wearing by a person.
• the ratio of the fibrous material to polymer particles is known to effect performance characteristics. In some cases, this ratio is between 75:25 and 90: 10 (see U.S. Patent No. 4,685,915, incorporated by reference for its teachings of diaper manufacture).
• Other disposable absorbent articles may be constructed in a similar fashion, such as for adult incontinence, feminine hygiene (sanitary napkins), tampons, etc. (see, for example, U.S. Patent Nos. 5,009,653, 5,558,656, and 5,827,255 incorporated by reference for their teachings of sanitary napkin manufacture).
• Low molecular- weight polyacrylic acid has uses for water treatment, flocculants, and thickeners for various applications including cosmetics and pharmaceutical preparations.
• the polymer may be uncrosslinked or lightly crosslinked, depending on the specific application.
• the molecular weights are typically from about 200 to about 1,000,000 g/mol.
• Preparation of these low molecular- weight polyacrylic acid polymers is described in U.S. Patent Nos. 3,904,685; 4,301,266; 2,798,053; and 5,093,472, each of which is incorporated by reference for its teachings relating to methods to produce these polymers.
• Acrylic acid may be co -polymerized with one or more other monomers selected from acrylamide, 2-acrylamido-2-methylpropanesulfonic acid, ⁇ , ⁇ -dimethylacrylamide, N- isopropylacrylamide, methacrylic acid, and methacrylamide, to name a few.
• the relative reactivities of the monomers affect the micro structure and thus the physical properties of the polymer.
• Co-monomers may be derived from 3-HP, or otherwise provided, to produce copolymers. Ulmann's Encyclopedia of Industrial Chemistry, Polyacrylamides and
• Acrylic acid can in principle be copolymerized with almost any free-radically polymerizable monomers including styrene, butadiene, acrylonitrile, acrylic esters, maleic acid, maleic anhydride, vinyl chloride, acrylamide, itaconic acid, and so on. End-use applications typically dictate the co-polymer composition, which influences properties.
• Acrylic acid also may have a number of optional substitutions on it, and after such substitutions be used as a monomer for polymerization, or co-polymerization reactions.
• acrylic acid (or one of its co -polymerization monomers) may be substituted by any substituent that does not interfere with the polymerization process, such as alkyl, alkoxy, aryl, heteroaryl, benzyl, vinyl, allyl, hydroxy, epoxy, amide, ethers, esters, ketones, maleimides, succinimides, sulfoxides, glycidyl and silyl (see U.S. Patent No. 7,678,869, incorporated by reference above, for further discussion).
• the following paragraphs provide a few non-limiting examples of copolymerization applications.
• Paints that comprise polymers and copolymers of acrylic acid and its esters are in wide use as industrial and consumer products. Aspects of the technology for making such paints can be found in U.S. Patent Nos. 3,687,885 and 3,891,591, incorporated by reference for its teachings of such paint manufacture.
• acrylic acid and its esters may form homopolymers or copolymers among themselves or with other monomers, such as amides, methacrylates, acrylonitrile, vinyl, styrene and butadiene.
• 'vehicle' or 'binder'
• 'vehicle' or 'binder'
• 'vehicle' aqueous solution
• solvent e.g., acetone, benzol, alcohols, etc., although these are not found in certain no VOC paints
• thickener e.g., acetone, benzol, alcohols, etc., although these are not found in certain no VOC paints
• additional additives depending on the conditions, applications, intended surfaces, etc.
• the weight percent of the vehicle portion may range from about nine to about 26 percent, but for other paints the weight percent may vary beyond this range.
• Acrylic-based polymers are used for many coatings in addition to paints.
• acrylic acid is used from 0.1-5.0%, along with styrene and butadiene, to enhance binding to the paper and modify rheology, freeze-thaw stability and shear stability.
• U.S. Patent Nos. 3,875,101 and 3,872,037 are incorporated by reference for their teachings regarding such latexes.
• Acrylate-based polymers also are used in many inks, particularly UV curable printing inks. For water treatment, acrylamide and/or hydroxy ethyl acrylate are commonly co -polymerized with acrylic acid to produce low molecular- weight linear polymers.
• 3-HP may be converted to 3-HP-CoA, which then may be converted into polymerized 3-HP with an enzyme having polyhydroxyacid synthase activity (EC 2.3.1.- class of enzymes).
• 1,3-propanediol can be made using polypeptides having oxidoreductase activity or reductase activity (e.g. , enzymes in the EC 1.1.1.- class of enzymes).
• a combination of (1) a polypeptide having aldehyde dehydrogenase activity (e.g., an enzyme from the 1.1.1.34 class) and (2) a polypeptide having alcohol dehydrogenase activity (e.g., an enzyme from the 1.1.1.32 class) can be used.
• Polypeptides having lipase activity may be used to form esters. Enzymatic reactions such as these may be conducted in vitro, such as using cell-free extracts, or in vivo.
• various embodiments of the present invention include conversion steps to any such noted downstream products of microbially produced 3-HP, including but not limited to those chemicals described herein and in the incorporated references (the latter for jurisdictions allowing this).
• one embodiment is making 3-HP molecules by the teachings herein and further converting the 3- HP molecules to polymerized-3-HP (poly-3-HP) or acrylic acid, and such as from acrylic acid then producing from the 3-HP molecules any one of polyacrylic acid (polymerized acrylic acid, in various forms), methyl acrylate, acrylamide, acrylonitrile, propio lactone, ethyl 3-HP, malonic acid, 1,3-propanediol, ethyl acrylate, n-butyl acrylate, hydro xypropyl acrylate, hydroxyethyl acrylate, isobutyl acrylate, 2-ethylhexyl acrylate, and acrylic acid or an acrylic acid ester to which an alkyl or aryl addition is made, and/or to which halogens, aromatic amines or amides, and aromatic hydrocarbons are added.
• polyacrylic acid polymerized acrylic acid, in various forms
• methyl acrylate acrylamide
• Stabilizing agents and/or inhibiting agents include, but are not limited to, e.g., phenolic compounds (e.g., dimethoxyphenol (DMP) or alkylated phenolic compounds such as di-tert- butyl phenol), quinones (e.g., t-butyl hydroquinone or the monomethyl ether of hydro quinone (MEHQ)), and/or metallic copper or copper salts (e.g., copper sulfate, copper chloride, or copper acetate).
• DMP dimethoxyphenol
• MEHQ monomethyl ether of hydro quinone
• metallic copper or copper salts e.g., copper sulfate, copper chloride, or copper acetate.
• Inhibitors and/or stabilizers can be used individually or in combinations as will be known by those of skill in the art.
• the one or more downstream compounds is/are recovered at a molar yield of up to about 100 percent, or a molar yield in the range from about 70 percent to about 90 percent, or a molar yield in the range from about 80 percent to about 100 percent, or a molar yield in the range from about 90 percent to about 100 percent.
• Such yields may be the result of single-pass (batch or continuous) or iterative separation and purification steps in a particular process.
• the methods of the present invention can also be used to produce downstream compounds derived from 3-HP, such as but not limited to, polymerized-3-HP (poly-3-HP), acrylic acid, polyacrylic acid (polymerized acrylic acid, in various forms), copolymers of acrylic acid and acrylic esters, acrylamide, acrylonitrile, propio lactone, ethyl 3-HP, malonic acid, and 1,3-propanediol. Also, among esters that are formed are methyl acrylate, ethyl acrylate, n-butyl acrylate, hydroxypropyl acrylate, hydroxyethyl acrylate, isobutyl acrylate, and 2-ethylhexyl acrylate.
• acrylic acid and/or other acrylate esters may be combined, including with other compounds, to form various known acrylic acid-based polymers.
• acrylic acid may be made from 3- HP via a dehydration reaction
• methyl acrylate may be made from 3-HP via dehydration and esterification, the latter to add a methyl group (such as using methanol)
• acrylamide may be made from 3-HP via dehydration and amidation reactions
• acrylonitrile may be made via a dehydration reaction and forming a nitrile moiety
• proprio lactone may be made from 3-HP via a ring-forming internal esterification reaction
• ethyl-3-HP may be made from 3-HP via esterification with ethanol
• malonic acid may be made from 3-HP via an oxidation reaction
• 1 ,3-propanediol may be made from 3-HP via a reduction reaction.
• the above mentioned downstream compounds may also be converted to consumer products, including but not limited consumer products such as diapers, carpet, paint, and adhesives, and the alike.
• acrylamide Another important product, acrylamide has been used in a number of industrial applications.
• Acrylamide may be produced from 3-HP, for example, without being limiting, via an esterification-amidation-dehydration sequence. Refluxing an alcohol solution of 3-HP in the presence of an acid or Lewis acid catalyst described herein would lead to a 3-HP ester. Treatment of the 3-HP ester with either an ammonia gas or an ammonium ion could yield 3- HP amide. Finally, dehydration of the 3-HP amide with dehydration reagents described earlier in this application could produce acrylamide. The steps mentioned herein may be rearranged to produce the same final product acrylamide. Polymerization of acrylamide can be achieved, for example and without being limiting, by radical polymerization.
• Polyacrylamide polymers have been widely used as additives for treating municipal drinking water and waste water. In addition, they have found applications in gel electrophoresis, oil- drilling, papermaking, ore processing, and the manufacture of permanent press fabrics.
• a variety of solvents may be used in the present invention as long as 3-HP is soluble in the chosen solvent.
• a solvent may be selected such that other impurities in a fermentation broth are less soluble in the solvent than 3-HP.
• the solvent comprises C1-C12 alcohols.
• the alcohols are aliphatic alcohols.
• the aliphatic alcohols may be primary, secondary, or tertiary alcohols. They may be linear or branched alcohols. They may be miscible or immiscible with water. Their boiling points may be in a range from about 30 °C to about 150 °C.
• Alcohol solvent may depend on many factors, for example but not limited to, the scale of the reaction, the product desired, and the reactor used.
• Non-alcohol organic solvents such as ethers, ketones or aldehydes may be used as extracting solvents for 3-HP when esterification reactions are not wanted. For example if 3-HP is the intended isolate.
• Non-limiting examples of such solvents are tetrahydrofuran, methyl ethyl ketone, methyl aldehyde, ethyl aldehyde, diethyl ether, propyl aldehyde, and acetone.
• an acid may be used to adjust pH and/or a catalyst to accelerate an organic transformation, such as an esterification reaction.
• Suitable acids include but are not limited to, acidic resins, acidic inorganic salts, and mineral acids.
• Non- limiting examples of mineral acids include sulfuric acid, hydrochloric acid, polyphosphoric acid, phosphoric acid and hydrobromic acid.
• Non- limiting examples of inorganic salts include copper sulfate, FeCl 3 and A1C1 3 .
• Non-limiting examples of acidic resins include AMBERLYST® resins, NAFIONTM resins, and acidic DO WEXTM resins.
• the pH of the mixture may be in a range of less than 0, less than 1 , less than 2, less than 3, less than 4, less than 5, less than 6, less than 7 or less than 8.
• the pH may be about 0, 1, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.6, or 7.0
• Step 101 A neutral pH fermentation broth was centrifuged (for example at 3250 G or greater) for at least 5 minutes to remove whole cells.
• Step 102 Water in the clarified fermentation broth was removed by evaporation. Evaporation was conducted by decreasing the pressure to about 60 mbar and heating to about 60°C. In addition, an atmospheric pressure at 100 °C was also effective for evaporation. The distilled water could then be re-used in the fermentation process.
• Step 103 After the removal of water, precipitated solids such as salts and proteins were separated either during the concentration using a scraped drum evaporator or after the concentration in a separate step using centrifugation or filtration to give a clarified
• Step 104 The clarified concentrated fermentation broth was acidified, for example with sulfuric acid to give an acidified broth, for example, a pH of about 2.0.
• Step 105 The acidified concentrated fermentation broth was extracted into a 3X volume of the alcohol, for example, butanol in three separate stages to achieve greater than 95% extraction efficiency. Upon complete extraction of 3-HP into the alcohol, a separate solid or viscous phase remained. The extraction represented a purification of the 3-HP away from organic insoluble impurities.
• Step 106 The 3-HP alcohol extract contained between 200 - 300 g/L 3-HP along with other organic acids. When butanol was used for an extraction solvent, enough acid was extracted into butanol that no extra acid was required for the esterification reaction. The butanol extract was refluxed at 118°C in the presence of a water trap to generate 3-HP butyl ester.
• Step 107 The 3-HP ester can be further processed to 3-HP amide using ammonia gas or an ammonium ion in an amidation type reaction.
• the use of an ester of 3-HP for the amidation reaction was advantageous over that of 3-HP in the acid form since the ester group is more reactive towards nitrogen-based nucleophiles than the carboxylic acid group.
• Step 108 The conversion of 3-HP amide via dehydration to acrylamide can be conducted using heat and/or catalyst with or without an external solvent.
• the temperature may be in a range of 25 °C to 250 °C.
• the catalyst can be an acid, such as a Lewis acid, an inorganic acid, or an organic acid, or a base such as a hydroxide or an amine, either organic or inorganic.
• the amount of catalyst could be in a range of about 0.1% to about 99%.
• a dehydration reagent such as molecular sieves or ortho-esters, may be added to facilitate the dehydration reaction.
• EXAMPLE 2 A SYSTEM AND METHOD FOR THE BIO-PRODUCTION
• FIG. 2 outlines a reactor system that can be used in the production of acrylamide from 3-HP.
• the reactor system 200 is comprised of a fermenter 201, a holding tank 202, three centrifuges 203, 206, and 209, a wiped film evaporator 205, an acid tank 208, a counter current extractor 211, an alcohol tank 212, a reactive distillation apparatus 214, a 3-HP ester tank 215, an ammonia tank 216, an acrylamide reactor 217 and an acrylamide tank 218.
• various components of system 200 are described below and depicted in FIG. 2, the components need not necessarily all be present, and in some cases may be present in a different order than the order shown in FIG. 2.
• 3-HP can be produced by the following bio -production method and system. This method involves the production of 3-HP through the use of bacterial cells during a fermentation process in the fermenter 201.
• the concentration of 3-HP may be in a range of 2-200 g/L, or at least 10 g/L.
• the whole cell broth from the fermentation process is transferred to the holding tank 202 prior to feeding into the centrifuge 203.
• the broth is centrifuged at 3250 G for 5 minutes or 1 million G for less than 1 minute to remove solids. After removing solids 204, the remaining liquid is transferred to a wiped film evaporator 205. Water is evaporated at skin temperature of 135 °C, vacuum of 25 mrnHg and RPM (revolutions per minute) of 250. The "skin temperature” refers to the operating temperature of the wiped film evaporator. The water is recycled and reused in the fermentation process.
• the concentrated fermentation broth contains 3-HP at a concentration of at least 50-200 g/L, such as at least 100 g/L.
• the concentrated broth is fed into the second centrifuge 206 to remove solids 207. Thereafter, a clarified concentrated fermentation broth is obtained.
• the pH of the clarified concentrated fermentation broth is adjusted with an acid from the acid tank 208.
• exemplary acids that can be used to adjuste the pH include but are not limited to, an inorganic acid, for example, sulfuric acid or phosphoric acid, may be used.
• Insoluble salts 210 are further removed using the third centrifuge 209.
• the 3-HP in the acidified clarified concentrate is extracted into an alcohol using the counter current extractor 211.
• Esterification is conducted in the reactive distillation apparatus 214 and the resulting 3-HP ester is distillated off and collected in 3-HP ester tank 215.
• the 3-HP ester undergoes an amidation and dehydration reaction in the amidation reactor 217 to produce acrylamide.
• the amidation reaction is carried out with ammonia gas from the ammonia tank 216.
• the production output of acrylamide may be at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 120, 150, 200, 300, or 500 tons per day.
• Dehydration reactions were set up using bentonite clay in a reaction vessel surrounded by an aluminum heating block.
• the aluminum heating block was used for improved heat transfer between the furnace and the reaction vessel.
• the aluminum heating block is a hollow cylinder machined from aluminum. It has an inner diameter of 1 ⁇ 2" to fit snuggly around the reaction vessel and an outer diameter of 3" to fit snuggly inside the furnace.
• the heating block is 15" in length, the same as the furnace.
• Reactor conditions such as temperature, flow rate, and pressure were recorded every 15 mins during each run.
• product sample were taken every 15 mins over the course of three hours during the run and analysis by HPLC or UV/Vis spectra analysis was performed. Analysis by UV/Vis spectra peaks at or around 230 nm, 275 nm, and 290 nm were used to determined 3-HP, acrylic acid, and MEHQ levels in a sample, respectively.
• the furnace temperature set-point started at 27 °C and then was raised to 300 °C after 2 hours and then maintained for the duration of the experiment, which was 7 hours total. With double insulation of the reactor inlet and outlet "T"s, a response to changes in furnace temperatures can be observed. The average inlet and outlet temperatures raise an average of 7 °C and 5 °C, respectively in response to the increased temperature. This is shown in FIG.5.
• FIG. 6 show the percent conversion (%) and percent yield (%) of the reactor system over the 7 hour time course.
• FIG. 7 shows the mass per 15 minute sampling period of 3-HP and acrylic acid (AA) in the reactor system over the 7 hour time course. The best
• the optimal period begins about 30 minutes after the furnace temperature is raised from 275 °C to 300 °C.
• FIG. 8 shows the "mass balance" of feed mass and product mass as percentages of 3-HP and acrylic acid mass in the reactor system during the 7 hour time course.

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• 2013
  • 2013-06-20 WO PCT/US2013/046900 patent/WO2013192453A1/en active Application Filing
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