HK1180329A - Processes for producing caprolactam and derivatives thereof from fermentation broths containing diammonium adipate or monoammonium adipate - Google Patents

Abstract

Processes for producing caprolactam (CL) and derivatives thereof from adipic acid (AA) obtained from fermentation broths containing diammonium adipate (DAA) or monoammonium adipate (MAA).

Description

Process for preparing caprolactam and derivatives thereof from fermentation broths containing diammonium adipate or monoammonium adipate

RELATED APPLICATIONS

The present invention claims priority from united states provisional application No. 61/355,197, filed on 16/6/2010, the subject matter of which is incorporated herein by reference.

Technical Field

The present application relates to a process for producing Caprolactam (CL) from a fermentation broth comprising diammonium adipate (DAA) or monoammonium adipate (MAA).

Background

Certain carbonaceous products of sugar fermentation are considered as alternatives to petroleum-derived materials for use as feedstocks for the manufacture of carbon-containing chemicals. One such product is Adipic Acid (AA). In view of such a process for the direct production of substantially pure AA from DAA-containing or MAA-containing broths, and the availability of such pure AA as a feedstock for the production of CL, it would be advantageous to provide a process for the production of CL and its derivatives in an economical and environmentally friendly manner.

Disclosure of Invention

The present invention provides a process for making CL from a clarified DAA-containing fermentation broth or a clarified MAA-containing fermentation broth comprising: distilling the broth at a temperature of >100 ℃ to about 300 ℃ and at superatmospheric pressure to form an overhead that comprises water and ammonia and a liquid bottoms that comprises AA and at least about 20wt% (weight percent) water; cooling and/or evaporating the bottoms to obtain a temperature and composition sufficient to cause the bottoms to separate into a liquid portion and a solid portion that is substantially pure AA; separating the solid portion from the liquid portion; contacting at least a portion of the solid portion with hydrogen, optionally in the presence of a solvent, in the presence of a hydrogenation catalyst and an ammonia source, at a temperature of about 25 ℃ to about 500 ℃ and a pressure of about 0.5MPa to about 40MPa, to produce CL.

The present invention also provides a process for making CL from a clarified DAA-containing fermentation broth or a clarified MAA-containing fermentation broth comprising: adding an ammonia separating solvent and/or a water azeotroping solvent to the fermentation broth; distilling the broth at a temperature and pressure sufficient to form an overhead that comprises water and ammonia, and a liquid bottoms that comprises AA and at least about 20wt% water; cooling and/or evaporating the bottoms to obtain a temperature and composition sufficient to cause the bottoms to separate into a liquid portion and a solid portion that is substantially pure AA; separating the solid portion from the liquid portion; contacting at least a portion of the solid portion with hydrogen, optionally in the presence of a solvent, in the presence of a hydrogenation catalyst and an ammonia source, at a temperature of about 25 ℃ to about 500 ℃ and a pressure of about 0.5MPa to about 40MPa, to produce CL.

Drawings

FIG. 1 is a block diagram of a process for making AA from DAA-containing fermentation broth or MAA-containing fermentation broth;

FIG. 2 is a graph showing AA solubility in water as a function of temperature;

fig. 3 is a flow diagram for preparing CL and at least one CL derivative from AA.

Detailed Description

It should be understood that at least a portion of the following description, unlike the appended claims, is intended to refer to representative examples of methods selected for illustration in the accompanying drawings and is not intended to define or limit the invention.

The method of the present invention may be understood by reference to fig. 1, which fig. 1 shows in block diagram form one representative embodiment 10 of the method of the present invention.

Growth vessel 12 is typically an in situ steam sterilized fermentor that may be used to culture a microbial culture (not shown) that is subsequently used to prepare a fermentation broth containing DAA, MAA, and/or AA. Such growth vessels are known in the art and are not discussed further.

The microbial culture can include a microorganism capable of producing AA from a fermentable carbon source (e.g., carbohydrate sugars). Representative examples of microorganisms include: coli (Escherichia coli or e. coli), Aspergillus niger (Aspergillus niger), Corynebacterium glutamicum (Corynebacterium glutamicum) (also known as Brevibacterium flavum), Enterococcus faecalis (Enterococcus faecalis), Veillonella parvula (Veillonella parvula), Actinobacillus succinogenes (Actinobacillus succinogenes), Paecilomyces Varioti (Paecilomyces Varioti), Saccharomyces cerevisiae (Saccharomyces cerevisiae), Candida tropicalis (Candida tropicalis), Bacteroides fragilis (Bacteroides fragilis), Bacteroides ruminicola (Bacteroides ruminicola), Bacteroides amyloliquefaciens (Bacteroides amyloliquefaciens), klebsiella pneumoniae (leptium pneumoniae), mixtures thereof, and the like.

Preferred microorganisms include: nonomadic strain OH23 of Candida tropicalis (Castellani) Berkhout with ATCC accession number 24887; ATCC accession No. 69875 E.coli (E.coli) AB2834/pKD136/pKD8.243A/pKD 8.292; coli cosmid clones comprising vectors expressing cyclohexanone monooxygenase with the amino acid sequence encoded by SEQ ID NO:1 from Acinetobacter (Acinetobacter) strain SE19 and shown by SEQ ID NO:2 and designated 5B12, 5F5, 8F6 and 14D 7; and yeast strains (hereinafter "Verdezyne yeast") commercially available from Verdezyne ltd (Carslbad, CA, usa) for the production of AA from alkanes and other carbon sources.

An AA-containing fermentation broth was prepared by culturing Candida tropicalis (Castellani) Berkhout anamorph strain OH23 with ATCC accession No. 24887 in a liquid medium containing 300mg of NH in 100ml of distilled water at 32 ℃₄H₂PO₄200mg KH₂PO₄100mg of K₂HPO₄50mg of MgSO 2₄·7H₂O, 1. mu.g biotin, 0.1% (w/v, weight/volume) yeast extract and about 1% (v/v, volume/volume) n-hexadecane. Other media, such as YM broth containing n-hexadecane, may also be used. In the literature: the procedure for the preparation of AA-containing fermentation broths from medium containing n-hexadecane by cultivation of Candida tropicalis (Castellani) Berkhout) anamorph strain OH23 with ATCC accession number 24887 is also described in Okuhura et al, 35 agr, biol. chem.1376(1971), the subject matter of which is incorporated herein by reference.

An AA-containing fermentation broth can also be prepared from the E.coli strain AB2834/pKD136/pKD8.243A/pKD8.292 with ATCC accession No. 69875. This can be achieved as follows. 1 liter of LB medium (in a 4L Erlenmeyer flask) containing IPTG (0.2 mM), ampicillin (0.05 g), chloramphenicol (0.02 g) and spectinomycin (0.05 g) was inoculated with 10ml of an overnight culture of cells of the E.coli strain AB2834/pKD136/pKD8.243A/pKD8.292 grown at 37 ℃ and 250rpm for 10 hours. The cells were harvested and resuspended in 1L M9 minimal medium containing 56mM D-glucose, shikimic acid (0.04 g), IPTG (0.2 mM), ampicillin (0.05 g), chloramphenicol (0.02 g) and spectinomycin (0.05 g). The culture may then be returned to 37 ℃ for culture. After resuspension in minimal medium, the pH of the culture can be closely monitored, especially during the initial 12 hours. When the culture reached a pH of 6.5, 5N NaOH or an appropriate amount of other base (e.g., ammonium hydroxide) was added to adjust the pH back to about 6.8. The pH of the culture should not be below 6.3 during the 48 hour accumulation period. After 24 hours in the medium, 12mM of cis, cis-muconate and 1mM of protocatechuic acid and 23mM of D-glucose were detected in the culture supernatant. After 48 hours in the medium, the cells of E.coli strain AB2834/pKD136/pKD8.243A/pKD8.292 can essentially replace 56mM D-glucose in the medium with 17mM cis, cis-muconate.

Cis, cis-muconate AA, which can then be synthesized by the microorganisms described below, can then be reduced to produce an AA-containing fermentation broth. 50mg of platinum carbon (10%) can be added to 6ml of cell-free culture supernatant from fermentation containing about 17.2mM of cis, cis-muconate. The sample may then be hydrogenated at room temperature and under a hydrogen pressure of 50psi for 3 hours to produce a fermentation broth containing AA. For example, a fermentation broth prepared in this manner may contain about 15.1mM AA. The procedure for the preparation of AA-containing fermentation broths by culturing cells of the E.coli strain AB2834/pKD136/pKD8.243A/pKD8.292, by means of cultivation in a medium containing D-glucose, is also described in the following documents: draths & Frost,116j.am.chem.soc.399 (1994); draths and Frost,18 biotechnol. prog.201 (2002); and patent US5,487,987 and patent US5,616,496, the subject matter of which is incorporated herein by reference.

An AA containing fermentation broth can also be prepared by culturing E.coli cosmid clones designated 5B12, 5F5, 8F6 and 14D7 and comprising a vector expressing the cyclohexanone monooxygenase SEQ ID NO:2 encoded by SEQ ID NO:1 of Acinetobacter strain SE19 in M9 minimal medium supplemented with 0.4% glucose as carbon source. The cells were cultured at 30 ℃ for 2 hours with shaking, and 330ppm of cyclohexanol was added to the medium. Subsequently, further incubation is performed at 30 ℃ for additional time periods, such as 2h, 4h, or 20h or other time periods. Patent US 6,794,165 also describes the step of preparing an AA-containing fermentation broth by culturing e.coli cosmid clones designated 5B12, 5F5, 8F6 and 14D7 and comprising a vector expressing cyclohexanone monooxygenase encoded by SEQ ID NO:1 of acinetobacter strain SE19 in a medium comprising D-glucose and cyclohexanol, the subject matter of which is incorporated herein by reference.

AA-containing fermentation broths can also be prepared using Verdezyne yeast strains commercially available from Verdezyne ltd (Carslbad, CA, usa) which, when cultured in media (e.g., SD media) containing alkanes or other carbon sources (e.g., sugars and plant-based oils), can produce AA as reported on 2/8 days 2010.

An AA-containing fermentation broth may also be prepared from escherichia coli or other microorganisms transformed with a nucleic acid encoding: succinyl-coenzyme A acetyl-coenzyme A acyltransferase; 3-hydroxyacyl-coa dehydrogenase; 3-hydroxyadipyl-coa dehydratase; 5-carboxy-2-pentenoyl-coenzyme a reductase; adipoyl-coa synthetase; phosphoadipylase/adipate kinase; adipoyl-coa transferase; or an adipoyl-coa hydrolase. AA containing fermentation broth can also be prepared from Escherichia coli or other microorganisms transformed with nucleic acids encoding: succinyl-coenzyme A acetyl-coenzyme A acyltransferase; 3-oxoadipyl-coenzyme a transferase; 3-oxoadipate reductase; 3-hydroxyadipate dehydratase; and 2-enoate reductase. AA containing fermentation broth can also be prepared from Escherichia coli or other microorganisms transformed with nucleic acids encoding: α -ketoadipyl-coenzyme a synthetase; phosphoketoadipylase/alpha-ketoadipate kinase or alpha-ketoadipyl-CoA acetyl-CoA transferase; 2-hydroxyadipoyl-coa dehydrogenase; 2-hydroxyadipoyl-coa dehydratase; 5-carboxy-2-pentenoyl-coenzyme a reductase; and adipoyl-coa synthetase; phosphotransferase adipyse/adipate kinase; adipoyl-CoA acetyl-CoA transferase or adipoyl-CoA hydrolase. AA containing fermentation broth can also be prepared from Escherichia coli or other microorganisms transformed with nucleic acids encoding: 2-hydroxyadipate dehydrogenase; 2-hydroxyadipoyl-coenzyme a synthetase; hydroxyadipylase phosphate/2-hydroxyadipate kinase or 2-hydroxyadipyl-coa: acetyl-coa transferase; 2-hydroxyadipoyl-coa dehydratase; 5-carboxy-2-pentenoyl-coenzyme a reductase; and adipoyl-coa synthetase; phosphoadipyl transferase/adipate kinase; adipoyl-coa acetyl-coa transferase; or an adipoyl-coa hydrolase.

Fermentation of E.coli or other microorganisms transformed with nucleic acids encoding these enzymes can be carried out using a variety of different carbon sources under standard conditions in standard media (e.g., M9 minimal media) under appropriate antibiotics or nutritional supplements necessary to maintain the transformed phenotype. The steps of preparing AA-containing fermentation broths by culturing e.coli or other microorganisms transformed with nucleic acids encoding these enzymes, suitable media and carbon sources are also described in patent US2009/0305364, the subject matter of which is incorporated herein by reference.

The steps of preparing a dicarboxylic acid (e.g. AA) -containing fermentation broth by culturing a strain of Saccharomyces cerevisiae or other strains, microbial strains, suitable media and carbon sources are also described in patent WO2010/003728, the subject matter of which is incorporated herein by reference.

Fermentable carbon sources (e.g., carbohydrates and sugars), optionally nitrogen sources and complex nutrients (e.g., corn steep liquor), additional media components (e.g., vitamins, salts, and other substances that enhance cell growth and/or product formation), and water may be added to growth vessel 12 for the growth and maintenance of the microbial culture. Generally, the microbial culture medium is grown under aerobic conditions, which are provided by blowing oxygen-rich gas (e.g., air, etc.). Typically, an acid (e.g., sulfuric acid, etc.) and ammonium hydroxide are provided for pH control during growth of the microbial culture.

In one example (not shown), the oxygen-rich gas is changed to an oxygen-deficient gas (e.g., CO)₂Etc.) while the aerobic conditions in growth vessel 12 (provided by blowing oxygen-rich gas) are switched to anaerobic conditions. The anaerobic environment may cause the fermentable carbon source to be biologically converted to AA in situ in growth vessel 12. Ammonium hydroxide is provided for pH control during bioconversion of the fermentable carbon source to AA. Due to the presence of ammonium hydroxide, the AA produced is at least partially (if not fully) neutralized to DAA, such that a fermentation broth comprising DAA is produced. Addition of CO₂Additional carbon sources for the preparation of AA may be provided.

In another example, the contents of the growth vessel 12 may be transferred to a separate bioconversion vessel 16 by means of the flow 14 to bioconvert the carbohydrate source to AA. Will be anoxic (e.g., CO)₂Etc.) blowing to the biological rotorThe vessel 16 is acidified to provide anaerobic conditions that initiate the production of AA. Ammonium hydroxide is provided for pH control during bioconversion of the carbohydrate source to AA. Due to the presence of ammonium hydroxide, the AA produced is at least partially neutralized to DAA, such that a fermentation broth comprising DAA is produced. Addition of CO₂Additional carbon sources for the preparation of AA are provided.

In another example, the bioconversion can be performed at a relatively low pH (e.g., 3-6). A base (ammonium hydroxide or ammonia) may be provided for pH control during bioconversion of the carbohydrate source to AA. Depending on the desired pH, AA is prepared, either due to the presence or absence of ammonium hydroxide, or at least partially neutralized to MAA, DAA, or a mixture comprising AA, MAA, and/or DAA. Thus, optionally, in an additional step, AA produced during bioconversion may be subsequently neutralized by providing ammonia or ammonium hydroxide to produce a fermentation broth comprising DAA. Thus, "DAA-containing fermentation broth" generally refers to a fermentation broth that includes DAA and possibly any number of other components (such as MAA and/or AA) added and/or produced by bioconversion or other methods. Similarly, "MAA-containing fermentation broth" generally refers to a fermentation broth that includes MAA and possibly any number of other components (such as DAA and/or AA) added and/or produced by bioconversion or other methods.

The fermentation broth resulting from the bioconversion of the fermentable carbon source (in either the growth vessel 12 or bioconversion vessel 16, depending on where the bioconversion occurs) typically contains insoluble solids, such as cellular biomass and other suspended matter, which are transferred to a clarification device 20 by means of flow 18 prior to distillation. The insoluble solids were removed to clarify the fermentation broth. This reduces or prevents plugging of subsequent distillation equipment. Insoluble solids may be removed by any one or combination of a variety of solid-liquid separation techniques, including but not limited to centrifugation and filtration (including but not limited to ultrafiltration, microfiltration, or depth filtration), alone. Filtration may be selected using techniques known in the art. The soluble inorganic compounds can be removed by any number of known methods such as, but not limited to, ion exchange, physical adsorption, and the like.

An example of centrifugation is a continuous disk centrifuge. After centrifugation, it may be useful to add a polishing filtration step, such as dead-end filtration or cross-flow filtration, which may include the use of filtration aids such as diatomaceous earth or the like, or more preferably ultrafiltration or microfiltration. The ultrafiltration or microfiltration membrane may be, for example, a ceramic or polymeric material. An example of a polymeric Membrane is SelRO MPS-U20P (pH stabilized ultrafiltration Membrane) manufactured by Koch Membrane Systems, Inc. (Koch Membrane Systems, great Eat 850, Wilmington, Mass., USA). It is a commercially available polyethersulfone membrane with a molecular weight cut-off of 25,000 daltons, typically operating at pressures of 0.35MPa to 1.38MPa (maximum pressure of 1.55 MPa) and at temperatures up to 50 ℃. Alternatively, a filtration step of ultrafiltration or microfiltration may be employed alone.

The resulting clarified DAA-containing fermentation broth or MAA-containing fermentation broth, substantially free of microbial culture and other solids, is transferred to distillation apparatus 24 via stream 22.

The clarified distillation broth should contain an amount of DAA that is at least a majority, preferably at least about 70wt%, more preferably 80wt% and most preferably at least about 90wt% of all diammonium dicarboxylate salts in the broth. The weight percent (wt%) of DAA and/or MAA to the total dicarboxylate salts in the fermentation broth may be determined by High Pressure Liquid Chromatography (HPLC) or other known methods.

Water and ammonia are removed as overheads from distillation apparatus 24 and at least a portion of the water and ammonia are optionally recycled to bioconversion vessel 16 (or growth vessel 12 operating in an anaerobic mode) via stream 26.

The particular distillation temperature and pressure are not critical so long as the distillation is conducted in a manner that ensures that the overhead of the distillation contains water and ammonia and that the bottoms of the distillation includes at least some AA and at least about 20wt% water. More preferred amounts of water are at least about 30wt% and even more preferred amounts are at least about 40 wt%. The rate of ammonia removal from the distillation step increases with increasing temperature and can also be increased by injecting steam (not shown) during distillation. The rate of ammonia removal during distillation can also be increased by performing the distillation under vacuum or by blowing the distillation apparatus with a non-reactive gas such as air, nitrogen, or the like.

The removal of water during the distillation step can be enhanced by the use of organic entrainers such as toluene, xylene, methylcyclohexane, methyl isobutyl ketone, cyclohexane, heptane and the like, provided that the bottoms contains at least about 20wt% water. If the distillation is carried out in the presence of an organic agent capable of forming an azeotrope, which azeotrope consists of water and the organic agent, the distillation produces a biphasic bottoms comprising an aqueous phase and an organic phase, in which case the aqueous phase may be separated from the organic phase and the aqueous phase is used as the bottoms of the distillation. By-products such as adipimide and adipamide are substantially avoided as long as the water content in the bottoms is maintained at a level of at least about 30 wt%.

The preferred temperature for the distillation step is in the range of about 50 c to about 300 c, depending on the pressure. A more preferred temperature range is from about 150 c to about 240 c, which is dependent on pressure. Distillation temperatures of about 170 ℃ to about 230 ℃ are preferred. "distillation temperature" refers to the temperature of the bottoms (which for a batch distillation may be the temperature when the final desired amount of overhead is withdrawn).

The addition of a water-miscible organic solvent or ammonia separating solvent facilitates the removal of ammonia at various distillation temperatures and pressures as discussed above. Such solvents include aprotic solvents, dipolar solvents, oxygen-containing solvents capable of forming inert hydrogen bonds. Examples include, but are not limited to: diglyme, triglyme, tetraglyme, sulfoxides such as dimethyl sulfoxide (DMSO), amides such as Dimethylformamide (DMF) and dimethylacetamide, sulfones such as dimethyl sulfone, α -butyrolactone (GBL), sulfolane, polyethylene glycol (PEG), butoxytriglycol, N-methylpyrrolidone (NMP), ethers such as dioxane and Methyl Ethyl Ketone (MEK), and the like. Such solvents aid in the removal of ammonia from the DAA or MAA of the clarified broth. Regardless of the distillation technique, it is important that the distillation be conducted in a manner that ensures that at least some MAA and at least about 20wt% water, and even more preferably at least about 30wt% water, remain in the bottoms. The distillation may be carried out at atmospheric pressure, sub-atmospheric pressure or super-atmospheric pressure.

Under other conditions, such as when the distillation is conducted in the absence of an entrainer or ammonia separation solvent, the distillation is conducted at super atmospheric pressure and at a temperature of from greater than 100 ℃ to about 300 ℃ to form an overhead that comprises water and ammonia and a liquid bottoms that comprises AA and at least about 20wt% water. Superatmospheric pressures typically fall in the range of greater than ambient atmospheric pressure to about 25 atmospheres. Advantageously, the amount of water is at least about 30 wt%.

The distillation may be a single stage flash distillation, a multi-stage distillation (i.e., a multi-stage tower distillation), or the like. Single stage flash evaporation may be carried out in any type of flash evaporator (e.g., wiped film evaporator, thin film evaporator, thermosiphon flash evaporator, forced circulation flash evaporator, and the like). The multistage distillation column can be realized by using trays, packing, and the like. The packing may be loose packing (e.g., Raschig rings, pall rings, and Bell saddles, etc.) or structured packing (e.g., Koch-Sulzer packing, Intelox packing, and Maillard packing (Mellapak), etc.). The trays can be of any design (e.g., sieve trays, valve trays, bubble cap trays, etc.). The distillation may be carried out in any number of theoretical stages.

If the distillation apparatus is a column, the configuration is not particularly critical and well-known rules can be used to design the column. The column can be operated in stripping mode, rectification mode or fractionation mode. The distillation may be carried out in batch mode, semi-continuous mode or continuous mode. In continuous mode, the fermentation broth is continuously fed to the distillation apparatus and the overhead and bottoms are continuously removed from the apparatus as they are formed. The distillate from the distillation is an ammonia/water solution and the bottoms of the distillation, which may also contain other fermentation by-product salts (i.e., ammonium acetate, ammonium formate, ammonium lactate, etc.) and color bodies, are liquid aqueous solutions of MAA and AA.

The bottoms of the distillation may be transferred via stream 28 to cooling means 30 and cooled by conventional means. The cooling technique is not critical. A heat exchanger (using heat recovery) may be used. The bottoms can be cooled down to about 15 ℃ using a flash cooler. Typically cooled to 15 c using a chilled coolant, such as a glycol solution, or, less preferably, brine. A concentration step may be included prior to cooling to help increase product yield. Further, known methods can be employed to combine concentration and cooling, such as vacuum evaporation and employing heat removal methods using integral cooling jackets and/or external heat exchangers.

It was found that the presence of some MAA in the liquid bottoms helps to induce, in a cooling manner, separation of the bottoms into a liquid portion in contact with a solid portion that at least "consists essentially of" AA (meaning that the solid portion is at least substantially pure crystalline AA) by reducing the solubility of AA in the liquid aqueous bottoms containing MAA. Figure 2 shows the solubility of AA in water. Thus, it was found that AA can crystallize more completely from an aqueous solution if some MAA is also present in the aqueous solution. The preferred concentration of MAA in such a solution is about 20 wt%. More preferred concentrations of MAA in such solutions range from ppm (parts per million) to about 3 wt%. This phenomenon allows AA to crystallize (i.e., the formation of a solid portion of the bottoms of the distillation) at a higher temperature than would be required in the absence of MAA.

The bottoms of the distillation is fed via stream 32 to separator 34 to separate the solid portion from the liquid portion. Separation can be achieved by pressure filtration (e.g., using a Nutsche-type pressure filter or Rosenmond-type pressure filter), centrifugation, or the like. The resulting solid product can be recovered as product 36 and, if desired, dried by standard methods.

After separation, it may be desirable to treat the solid portion to ensure that no liquid portion remains on the surface of the solid portion. One way to minimize the amount of liquid fraction remaining on the surface of the solid fraction is to wash the separated solid fraction with water and dry the resulting washed solid fraction (not shown). A convenient way to wash the solid fraction is to use a so-called "basket centrifuge" (not shown). A suitable basket centrifuge is commercially available from the Western States Machine Company (Hamilton, Ohio, USA).

The liquid portion of the distilled bottoms 34 (i.e., the mother liquor) may contain residual dissolved AA, any unconverted MAA, any fermentation byproducts (such as ammonium acetate, ammonium lactate, or ammonium formate), and other minor impurities. The liquid portion may be sent to downstream equipment 40 via stream 38. In one example, the downstream apparatus 40 may be an apparatus for forming a deicing agent, for example, by treating the mixture with an appropriate amount of potassium hydroxide to convert an ammonium salt to a potassium salt. The ammonia produced in this reaction can be recovered for reuse in the bioconversion vessel 16 (or growth vessel 12 operating in an anaerobic mode). The resulting potassium salt mixture is valuable as a de-icing and anti-icing agent.

The mother liquor from the solids separation step 34 may be recycled (or partially recycled) to the distillation unit 24 via stream 42 to further enhance recovery of AA and further convert MAA to AA.

The solid part of the crystallization induced by cooling is essentially pure AA and can therefore be used for the known uses of AA.

HPLC can be used to detect the presence of nitrogen-containing impurities such as adipamide and adipimide. The purity of AA can be determined by elemental carbon and nitrogen analysis. Ammonia electrodes can be used to determine crude approximation of AA purity.

Depending on the environment and various operational inputs, there are situations where the fermentation broth may be a clarified MAA-containing fermentation broth or a clarified AA-containing fermentation broth. In these cases, it may be advantageous to add MAA, DAA, and/or AA, and optionally ammonia and/or ammonium hydroxide, to these broths to facilitate the production of substantially pure AA. For example, the working pH of the broth can be set so that the broth is a MAA-containing broth or an AA-containing broth. MAA, DAA, AA, ammonia and/or ammonium hydroxide may be added to these broths to obtain a broth pH preferably less than 6 to facilitate the preparation of substantially pure AA as described above. In one particular form, it is particularly advantageous to recycle AA, MAA and water from the liquid bottoms resulting from distillation step 24 into the fermentation broth and/or clarified fermentation broth. With respect to MAA-containing fermentation broth, such fermentation broth generally means that the fermentation broth includes MAA added and/or produced by bioconversion or other methods and possibly any number of other ingredients (such as DAA and/or AA).

As shown in fig. 3, a stream comprising AA can be contacted with various reactants and catalysts at selected temperatures and pressures to produce CL. AA can be dissolved or suspended in water or a solvent (e.g., dioxane) for use in downstream reactions (e.g., conversion to CL). By adding ammonia source (e.g. NH)₃Or NH₄OH), such solutions or suspensions that can convert AA (and MAA to DAA). Thus, a solution or suspension of AA can be dehydrated to form an amide of AA, which is subsequently hydrogenated to form CL.

CL can be prepared by various methods, for example the method disclosed in patent GB778,253. Patent GB778,253 discloses that AA, adipic diamide or diamide-forming derivatives of AA can be converted to CL in a single stage. At elevated temperatures, preferably not exceeding 220 ℃, and in the presence of ammonia and a hydrogenation catalyst and under pressure, AA, adipic acid diamide or a diamide-forming derivative of AA in liquid form may be treated with hydrogen. As expected, this process does not produce Hexamethylenediamine (HMD), but rather CL with ammonia removed. Adipic acid diamide or its diammonium salt can be used as starting material, or AA or diamide-forming derivatives of AA (such as diacid chlorides or diesters) are converted to adipic acid diamide by addition of ammonia and then to CL. The subject matter and content of the above-mentioned patent GB778,253 is incorporated herein by reference.

While only CL can be prepared as described above, CL and other useful materials, such as HMD, can also be prepared. An example can be found in patent JP49/019250, the subject matter of which is incorporated herein by reference. By using ammonia (NH) gas in the presence of ruthenium (Ru) metal catalyst₃) And hydrogen (H)₂) Treatment of AA, adipamide, DAA, or alkyl adipate can produce CL and HMD simultaneously. One embodiment discloses: at 240 ℃ at 60kg/cm²Hydrogen gas (H) of specification₂) Then, AA (36.5 g), H₂O (4.5 g), liquid ammonia (255 g) and activated carbon (20 g) containing 5% Ru for 4 hours. This gave 9.2g CL and 7.7g HMD. The distillation residue containing AA and its derivatives (e.g. aminocaproic acid) was recovered to provide additional 4.4g CL and 3.7g HMD.

Furthermore, CL can be prepared from adipamide (e.g. a diamide of AA or a monoamide of AA) as also disclosed in patent GB778,253. For example, patent GB778,253 states that a suspension of 180g of adipamide in about 3 liters of technical dioxane is treated with 45g of Raney nickel at 220 ℃ under a hydrogen pressure of 250atm in a 5 liter stirred autoclave. The pressure was increased to about 380 atm. The heating was stopped after 15 hours. The autoclave was cooled and the product was separated from the catalyst. After the dioxin was distilled off, light oil was fractionated out in vacuo. After a few drops of the first fraction, the CL, which has a melting point of 69 ℃, is distilled off and crystallized in the boiling range from 120 ℃/6mm to 130 ℃/6 mm. The CL can then be polymerized by known methods to a polyamide having a melting point of about 220 ℃.

Hydrogenation catalysts for converting AA to CL can be made more active to enhance the activity or selectivity of the catalyst. The promoter may be incorporated into the catalyst during any stage of the chemical treatment of the catalyst component. Chemical promoters typically enhance the physical or chemical function of the catalyst, but chemical promoters may also be added to prevent undesirable side reactions. For example, suitable promoters include metals selected from tin, zinc, copper, rhenium, gold, silver, and combinations thereof. Other promoters which may be used are elements selected from groups I and II of the periodic table.

The catalyst may be supported or unsupported. A supported catalyst is one in which the active catalyst is deposited on the support material by a number of methods, for example spraying, rinsing or physical mixing, followed by drying, calcination and, if necessary, activation by methods such as reduction or oxidation. Materials often used as supports can be porous solids with a large total surface area (external and internal) that can provide a high concentration of active sites per unit weight of catalyst. The catalyst support may enhance the function of the catalyst. The supported metal catalyst is a supported catalyst in which the catalyst is a metal.

The catalyst not supported on the catalyst support material is an unsupported catalyst. For example, the unsupported catalyst may be platinum black or(W.R.Grace&Co, columbia, MD) catalyst. Since alloys containing active and leachable metals (usually aluminum) are selectively leached, the metal is removed from the alloyThe catalyst has a high surface area.The catalyst has a high activity due to a high specific surface area and allows the use of lower temperatures in the hydrogenation reaction.The active metals of the catalyst include nickel, copper, cobalt, iron, rhodium, ruthenium, rhenium, osmium, iridium, platinum, palladium, mixtures thereof, and combinations thereof.

Promoter metals may also be added to the baseIn metal to influenceSelectivity and/or activity of the catalyst. ForThe promoter metal of the catalyst may be selected from transition metals from groups IIIA to VIIIA, IB and IIB of the periodic table of elements. Examples of promoter metals include chromium, molybdenum, platinum, rhodium, ruthenium, osmium, and palladium, typically comprising about 2% of the total weight of the metal.

The catalyst support may be any solid inert material including, but not limited to: oxides such as silica, alumina and titania; barium sulfate; calcium carbonate and carbon. The catalyst support may be in the form of a powder, granules, pellets, or the like.

Preferred support materials may be selected from carbon, alumina, silica-alumina, silica-titania, titania-alumina, barium sulfate, calcium carbonate, strontium carbonate and mixtures thereof. The supported metal catalyst may also have a support material made of one or more compounds. More preferred supports are carbon, titania and alumina. More preferred supports are those having a surface area greater than about 100m²Carbon per gram. Further preferred supports are those having a surface area greater than about 200m²Carbon per gram. Preferably, the carbon has an ash content of less than about 5% by weight of the catalyst support. The ash content is the inorganic residue remaining after incineration of the carbon (expressed as a percentage of the original weight of the carbon).

The preferred amount of metal catalyst in the supported catalyst can be from about 0.1% to about 20% of the supported catalyst based on the weight of the metal catalyst plus the weight of the support. More preferred metal catalyst content ranges from about 1% to about 10% of the supported catalyst.

The combination of metal catalyst and support system may comprise any one of the metals mentioned herein and any one of the supports mentioned herein. Preferred combinations of metal catalyst and support include palladium on carbon, palladium on alumina, palladium on titania, platinum on carbon, platinum on alumina, platinum on silica, iridium on carbon, iridium on alumina, rhodium on carbon, rhodium on silica, rhodium on alumina, nickel on carbon, nickel on alumina, nickel on silica, rhenium on carbon, rhenium on silica, rhenium on alumina, ruthenium on carbon, ruthenium on alumina, and ruthenium on silica.

A further preferred combination of metal catalyst and support comprises ruthenium on carbon, ruthenium on alumina, palladium on carbon, palladium on alumina, palladium on titania, platinum on carbon, platinum on alumina, rhodium on carbon, and rhodium on alumina.

Generally, the hydrogenation reaction can be carried out at a temperature of about 100 ℃ to about 500 ℃ in a reactor maintained at a pressure of about 6MPa to about 20 MPa.

The process for hydrogenating a feed containing AA or MAA using a catalyst can be carried out by various modes of operation known in the art. Therefore, the whole hydrogenation process can be carried out using a fixed bed reactor, various types of slurry stirring reactors (whether of gas stirring type or mechanical stirring type), or the like. The hydrogenation process may be carried out in a batch mode or a continuous mode, wherein the aqueous phase containing the hydrogenation precursor is contacted with a gaseous phase containing hydrogen at elevated pressure and a solid catalyst in the form of particles.

Temperature, solvent, catalyst, reactor configuration, pressure and mixing ratio are parameters that can affect conversion and selectivity. The relationship between these parameters can be adjusted to achieve the desired conversion, reaction rate and selectivity in the reaction of the process.

Preferred temperatures are from about 25 ℃ to 500 ℃, more preferably from about 100 ℃ to about 400 ℃, and most preferably from about 150 ℃ to 400 ℃. The pressure is preferably from about 0.5MPa to about 40 MPa.

The process and/or conversion may be performed in batch mode, sequential batch mode (i.e., a series of batch reactors), or in continuous mode in any equipment typically used for continuous processes. The condensed water formed as a reaction product is removed by separation methods commonly used for such separations.

As shown in fig. 4, CL can be converted to a polyamide (e.g., nylon 6). One method of such transformation is disclosed in patent JP2008/144075, the subject matter of which is incorporated herein by reference. The method includes polymerizing a feedstock composition containing at least CL and water. The raw material composition also comprises any one combination selected from the following three combinations as an end-capping agent: (a) at least one monocarboxylic acid compound and at least one primary or secondary monoamine compound, (b) at least one monocarboxylic acid compound and at least one primary or secondary diamine compound, and (c) at least one dicarboxylic acid compound and at least one primary or secondary monoamine compound. The feedstock composition may be heated at a temperature of at least about 240 ℃ to initiate polymerization.

Examples

The process of the present invention is illustrated by the following non-limiting representative examples.

The use of synthetic DAA solutions is considered a good model for the properties of the actual fermentation broth due to the solubility of typical fermentation byproducts in the actual fermentation broth in the process of the invention. The main by-products produced during fermentation are ammonium acetate, ammonium lactate and ammonium formate. Ammonium acetate, ammonium lactate and ammonium formate are significantly more soluble in water than AA, and all three are typically present in the fermentation broth at a concentration of less than 10% of the DAA concentration. Furthermore, even when acids (acetic acid, formic acid and lactic acid) are formed during the distillation step, these acids are miscible with water and will not crystallize from water. This means that the AA is saturated and crystallizes from solution (i.e., a solid portion is formed), leaving the acid impurities dissolved in the mother liquor (i.e., a liquid portion).

Example 1

This example shows the conversion of DAA to MAA.

A1L round bottom flask was charged with 800g of a synthetic 4.5% DAA solution. The flask was equipped with a five-plate Oldershaw section (a five tray Oldershaw section) with a distillation head at the top. The distillate was collected in an ice cold receiver. The contents of the flask were heated using a heating mantle and stirred using a magnetic stirrer. Distillation was started and 719.7 grams of distillate were collected. The distillate was titrated and shown to be a 0.29% ammonia solution (i.e., about 61% conversion of DAA to MAA). The hot residue (76 g) was removed from the flask and placed in an erlenmeyer flask over the end of a week while slowly cooling to room temperature with stirring. Then, with stirring, the contents were cooled to 15 ℃ and held for 60 minutes, then cooled to 10 ℃ and held for 60 minutes, and finally cooled to 5 ℃ and held for 60 minutes. The solid was filtered and dried in a vacuum oven at 75 ℃ for 2 hours to give 16.2 g of a solid. Analysis of the ammonia content of the solid by ammonia electrodes showed a molar ratio of ammonia to AA of about 1: 1.

Example 2

This example shows the conversion of MAA to AA.

A300 ml Parr autoclave was charged with 80g of the synthesized MAA and 124g of water. The autoclave was sealed and the contents were stirred and heated to about 200 ℃ (autogenous pressure about 203 psig). Once the contents reached this temperature, water was fed into the autoclave at a rate of about 2 g/min and steam was removed from the autoclave at a rate of about 2 g/min using a back pressure regulator. The vapor leaving the autoclave was condensed and collected in a receiver. The autoclave was operated under these conditions until a total of 1210g of water and 1185g of distillate had been fed. The contents of the autoclave (209 g) were partially cooled and removed from the reactor. The slurry was stirred in an erlenmeyer flask at room temperature overnight. The slurry was then filtered and the solids were rinsed with 25g of water. The moist solid was dried in a vacuum oven at 75 ℃ for 1 hour to give 59g of AA product. Analysis by an ammonium ion electrode showed 0.015mmol ammonium ions per gram of solid. The melting point of the recovered solid was 151 ℃ to 154 ℃.

Example 3

This example shows the conversion of DAA to MAA in the presence of a solvent.

36.8g of distilled water and 19.7g of concentrated ammonium hydroxide were charged to a beaker. Then, 23.5g of adipic acid was slowly added. The mixture was stirred to form a clear solution, which was then placed in a 500mL round bottom flask containing a stir bar. Triglyme (80 g) was then added to the flask. The flask was then equipped with five trays 1 "oldzod with a distillation head at the top of the oldzod. The distillation head was equipped with an ice-bath cooled receiver. The distillation flask was also equipped with an addition funnel containing 150g of distilled water. The contents were then stirred and heated using a heating mantle. When distillate began to appear, water in the addition funnel was added dropwise to the flask at the same rate that the distillate was removed. Distillation was stopped when all the water in the addition funnel had been added. A total of 158g of distillate had been collected. Titration measurements of the distillate showed an ammonia content of 1.6%. This corresponds to 46% of the ammonia charged. In other words, the residue was a monoammonium adipate/diammonium adipate mixture in a ratio of 91/9. After the residue was cooled to room temperature, it was placed in a 250mL erlenmeyer flask and slowly cooled to 5 ℃ with stirring. The slurry was filtered and the wet crystals were then dried in a vacuum oven for 2 hours to give 5.5g of a solid. Solid analysis showed that the ratio of ammonium ion to adipate ion was essentially 1:1 (i.e., monoammonium adipate).

Example 4

This example shows the conversion of MAA to AA in the presence of a solvent.

The beaker was charged with 46.7g of distilled water and 9.9g of concentrated ammonium hydroxide. Then, 23.5g of adipic acid was slowly added. The mixture was stirred to form a clear solution, which was then placed in a 500mL round bottom flask containing a stir bar. Triglyme (80 g) was then added to the flask. The flask was then equipped with five trays 1 "oldzod with a distillation head at the top of the oldzod. The distillation head was equipped with an ice-bath cooled receiver. The retort was also equipped with an addition funnel containing 1800g of distilled water. The contents were then stirred and heated using a heating mantle. When distillate began to appear, water in the addition funnel was added dropwise to the flask at the same rate that the distillate was removed. Distillation was stopped when all the water in the addition funnel had been added. 1806.2g of distillate had been collected in a lump. Titration measurements of the distillate showed an ammonia content of 0.11%. This corresponds to 72% of the ammonia charged. In other words, the residue is a mixture of adipic acid/monoammonium adipate in a ratio of 72/28. The residue was placed in an erlenmeyer flask, cooled to 0 ℃ with stirring, and left to stand for 1 hour. The slurry was filtered to give 18.8g of wet cake and 114.3g of mother liquor. The solid was then dried under vacuum at 80 ℃ for 2 hours to give 13.5g of a solid. The solid was then dissolved in 114g of hot water and then cooled to 5 ℃ with continued stirring for 45 minutes. The slurry was filtered to give 13.5g of wet solids and 109.2g of mother liquor. The solid was dried under vacuum at 80 ℃ for 2 hours to give 11.7g of a dried solid. Analysis of the solids showed an ammonium ion content of 0.0117mmol/g (i.e., substantially pure adipic acid).

Although the method of the present invention has been described in connection with specific steps and forms thereof, it should be understood that a wide range of equivalents may be substituted for the specific elements and steps described herein without departing from the spirit and scope of the invention as described in the appended claims.

Claims (6)

1. A process for producing caprolactam CL from a clarified DAA-containing fermentation broth or a clarified MAA-containing fermentation broth comprising:

(a) distilling the broth at a temperature of >100 ℃ to about 300 ℃ and at superatmospheric pressure to form an overhead that comprises water and ammonia and a liquid bottoms that comprises AA adipate and at least about 20wt% water;

(b) cooling and/or evaporating the bottoms to obtain a temperature and composition sufficient to cause the bottoms to separate into a liquid portion and a solid portion that is substantially pure AA;

(c) separating the solid portion from the liquid portion; and

(d) contacting at least a portion of the solid portion with hydrogen, optionally in the presence of a solvent, in the presence of a hydrogenation catalyst and an ammonia source, at a temperature of about 25 ℃ to about 500 ℃, and at a pressure of about 0.5MPa to about 40MPa, to produce the CL.

2. A process for making CL from a clarified DAA-containing fermentation broth or a clarified MAA-containing fermentation broth comprising:

(a) adding an ammonia separating solvent and/or a water azeotroping solvent to the fermentation broth;

(b) distilling the broth at a temperature and pressure sufficient to form an overhead that comprises water and ammonia, and a liquid bottoms that comprises AA and at least about 20wt% water;

(c) cooling and/or evaporating the bottoms to obtain a temperature and composition sufficient to cause the bottoms to separate into a liquid portion and a solid portion that is substantially pure AA;

(d) separating the solid portion from the liquid portion; and

(e) contacting at least a portion of the solid portion with hydrogen, optionally in the presence of a solvent, in the presence of a hydrogenation catalyst and an ammonia source, at a temperature of about 25 ℃ to about 500 ℃, and at a pressure of about 0.5MPa to about 40MPa, to produce the CL.

3. The method of claim 1 or 2, wherein preparing the CL comprises: dehydrating at least a portion of the solid portion in the presence of a source of ammonia to produce an amide of AA, followed by hydrogenation of the amide to form the CL.

4. The method of any one of claims 1-3, further comprising converting the CL to nylon 6.

5. The process according to claim 1 or 2, wherein the fermentation broth is obtained by fermentation of a carbon source in the presence of a microorganism selected from the group consisting of: ATCC accession No. 24887 Nonelida (Castellani) Nonelida strain OH 23; ATCC accession No. 69875 E.coli AB2834/pKD 136/pKD8.243A/pKD8.292; coli cosmid clone 5B12 comprising a vector expressing cyclohexanone monooxygenase encoded by SEQ ID No. 1; coli cosmid clone 5F5 comprising a vector expressing cyclohexanone monooxygenase encoded by SEQ ID No. 1; coli cosmid clone 8F6 comprising a vector expressing cyclohexanone monooxygenase encoded by SEQ ID No. 1; escherichia coli cosmid clone 14D7 comprising a vector expressing cyclohexanone monooxygenase encoded by SEQ ID NO: 1; and Verdezyne yeast.

6. The process of claim 2, wherein the broth is distilled in the presence of an ammonia separating solvent which is at least one selected from the group consisting of diglyme, triglyme, tetraglyme, sulfoxides, amides, sulfones, Polyethyleneglycol (PEG), butoxytriglycol, N-methylpyrolidone (NMP), ethers, and Methyl Ethyl Ketone (MEK) or in the presence of a water azeotroping solvent which is at least one selected from the group consisting of toluene, xylene, methylcyclohexane, methyl isobutyl ketone, hexane, cyclohexane and heptane.