WO2014129144A1 - アミド化合物の製造方法 - Google Patents
アミド化合物の製造方法 Download PDFInfo
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- WO2014129144A1 WO2014129144A1 PCT/JP2014/000718 JP2014000718W WO2014129144A1 WO 2014129144 A1 WO2014129144 A1 WO 2014129144A1 JP 2014000718 W JP2014000718 W JP 2014000718W WO 2014129144 A1 WO2014129144 A1 WO 2014129144A1
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- nitrile
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P13/00—Preparation of nitrogen-containing organic compounds
- C12P13/02—Amides, e.g. chloramphenicol or polyamides; Imides or polyimides; Urethanes, i.e. compounds comprising N-C=O structural element or polyurethanes
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/02—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
- C07C233/09—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to carbon atoms of an acyclic unsaturated carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F20/00—Homopolymers and copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride, ester, amide, imide or nitrile thereof
- C08F20/02—Monocarboxylic acids having less than ten carbon atoms, Derivatives thereof
- C08F20/52—Amides or imides
- C08F20/54—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide
- C08F20/56—Acrylamide; Methacrylamide
Definitions
- the present invention relates to a method for producing an amide compound, and specifically relates to a method for producing a corresponding amide compound from a nitrile compound using a biocatalyst.
- Amide compounds are widely used as industrially important substances.
- acrylamide is widely used as a flocculant for wastewater treatment, a paper strength enhancer, a petroleum recovery agent, and a methacrylamide as a paint and an adhesive.
- Patent Document 1 proposes aimed at improving the enzyme activity of nitrile hydratase (Patent Document 1), suppressing the decrease in activity due to temperature, and resistance to amide compounds (Patent Document 2).
- Patent Document 2 proposes proposals aimed at improving the enzyme activity of nitrile hydratase (Patent Document 1), suppressing the decrease in activity due to temperature, and resistance to amide compounds (Patent Document 2).
- Patent Documents 3 to 5 there are reports of identifying organic impurities that affect the activity in nitrile compounds and suppressing the decrease in activity.
- Patent Document 3 proposes a technique for reducing the concentration of benzene present in a nitrile compound.
- Patent Documents 4 and 5 for reducing the concentration of hydrocyanic acid in a nitrile compound has been proposed.
- the amide compound is efficiently produced by reducing the zinc concentration in the nitrile compound. We found that it can be manufactured.
- the present invention relates to the following [1] to [15].
- the zinc concentration in the nitrile compound is 0.4 ppm or less, preferably 0.3 mmp or less, more preferably Is a method for producing an amide compound, characterized by being 0.2 ppm or less;
- Production of amide compound according to [1] or [2], wherein the concentration of hydrocyanic acid in the nitrile compound is 1.5 ppm or less, preferably 1.0 ppm, more preferably 0.8 ppm or less.
- a process for producing an amide compound of [7] The method for producing an amide compound according to any one of [1] to [6], wherein the nitrile compound is acrylonitrile and the amide compound is acrylamide; [8]
- the biocatalyst having nitrile hydratase activity is an animal cell, plant cell, organelle, or microorganism of microorganism having nitrile hydratase activity, or a processed product thereof [1] to [7]
- a method for producing the amide compound according to any one of the above; [9] The method for producing an amide compound according to [8], wherein the microorganism having nitrile hydratase activity is Rhodococcus bacteria or Escherichia coli; [10]
- the amide compound according to [8] or [9], wherein the biocatalyst having nitrile hydratase activity is a cell of a microorganism expressing nitrile hydratase
- the biocatalyst having nitrile hydratase activity is 4 to 20% by mass, preferably 5 to 15% by mass, more preferably 5 to 10% by mass, and still more preferably 8% by mass as dry cells.
- the decrease in the activity of nitrile hydratase can be suppressed, and the corresponding amide compound can be efficiently produced from the nitrile compound.
- nitrile hydratase refers to an enzyme capable of hydrolyzing a nitrile compound to produce a corresponding amide compound.
- the biocatalyst having nitrile hydratase activity may be a nitrile hydratase protein itself, but may also be animal cells, plant cells, organelles, or microbial cells, and processed products thereof.
- Examples of the treated product include animal cells, plant cells, cell organelles, crushed materials obtained by disrupting microorganisms, or enzymes (elementary enzymes or purified enzymes) extracted from the cells; animal cells, plant cells, cells Organelles, microbial cells or enzymes immobilized on a carrier; and the like.
- Examples of the immobilization method include a comprehensive method, a crosslinking method, a carrier binding method, and the like.
- the inclusion method is a method of coating with a polymer film.
- the crosslinking method is a method in which an enzyme is crosslinked with a reagent having two or more functional groups (polyfunctional crosslinking agent).
- the carrier binding method is a method of binding an enzyme to a water-insoluble carrier.
- Examples of the simple substance (immobilization carrier) used for immobilization include gas beads, silica gel, polyurethane, polyacrylamide, polyvinyl alcohol, color ginnan, alginic acid, agar, and gelatin.
- microorganisms include, for example, the genus Rhodococcus having the nitrile hydratase activity, the genus Gordona, the genus Pseudomonas, the genus Pseudonocardia, the genus Geobacillus, and the Bacillus genus.
- (Bacillus) genus Bacteridium genus, Micrococcus genus, Brevibacterium genus, Corynebacterium genus, Nocardia genus, Microbacteria genus, Microbacterium genus Fusarium genus, Agrobacterium (Ag) genus obacterium, genus Acinetobacter, genus Xanthobacter, genus Streptomyces, genus Rhizobium, genus Klebsiella e, genus Enterobacter e And microorganisms belonging to the genus Pantoea, the genus Candida, the genus Aeromonas, the genus Citrobacter, the genus Achromobacter and the like.
- Nocardia sp. Described in Japanese Patent Publication No. 56-17918 is disclosed. N-775, Rhodococcus rhodochrous J-1 described in Japanese Examined Patent Publication No. 06-55148, Rhodococcus rhodochrous NCIMB41164 strain described in International Publication Pamphlet WO2005 / 054456, Japanese Patent Laid-Open No. 05-30982 Klebsiella sp. Aeromonas sp. Described in MCI 2609 and JP-A No. 05-30983. MCI 2614, Citrobacter freundii MCI 2615 described in JP-A No.
- Rhodococcus rhodochrous J-1 strain described in Japanese Patent Publication No. 06-55148 has the accession number “FERM BP-1478” on September 18, 1987. It is deposited with Tsukuba City, Ibaraki Prefecture 1-1-1 Central No. 6 (hereinafter the same).
- Rhodococcus rhodochrous NCIMB41164 strain described in International Publication Pamphlet WO 2005/054456 is National Collection of Industrial, Food and Marine Bacteria, Ltd. (NCIMBLdB) on March 5, 2003. 9YA) as deposit number NCIMB 41164.
- Pseudocardia thermophila JCM3095 described in Japanese Patent Application Laid-Open No. 09-275978 is a patent number of FERM BP-5785 as an accession number “FERM BP-5785” on February 7, 1996. Deposited at the Biological Depositary Center (6th East 1-1-1 Tsukuba City, Ibaraki Prefecture).
- one kind selected from the microorganisms may be used alone or in combination of two or more kinds.
- genes encoding nitrile hydratase can be introduced and expressed in microbial cells by conventional molecular biology techniques (see Sambrook, Fritscj and Maniatis, “Molecular” for these molecular techniques). Cloning: A Laboratory Manual “2nd Edition (1989), Cold Spring Harbor Laboratory Press). That is, in the present invention, an enzyme obtained by expressing a nucleic acid encoding natural nitrile hydratase (wild type) or a mutant (improved type) thereof in a microbial cell can also be used. In this invention, 1 type selected from the said enzyme can be used individually or in combination of 2 or more types.
- amino acid sequence of wild-type nitrile hydratase is published in NCBI databases such as GenBank (http://www.ncbi.nlm.nih.gov/).
- accession number (Accession No.) of the ⁇ subunit derived from Rhodococcus rhodochrous J1 is “P21219”, and the accession number of the ⁇ subunit is “P21220”.
- accession number of the ⁇ subunit derived from Rhodococcus rhodochrous M8 is “ATT79340”, and the accession number of the ⁇ subunit is “AAT79339”.
- accession number of the ⁇ subunit derived from Pseudomonas thermophila JCM3095 is “1IRE A”
- accession number of the ⁇ subunit is “1IREB”.
- transformants into which a wild-type nitrile hydratase gene has been introduced include Escherichia coli MT10770 (FERM P-14756) transformed with a nitrile hydratase belonging to the genus Achromobacter (JP-A-8-266277), E. coli MT10822 (FERM BP-5785) (JP 9-275978 A) or Rhodococcus rhodochrous species nitrile hydratase transformed with a nitrile hydratase belonging to the genus Pseudonocardia (JP 4) No. -21379)), but is not limited thereto.
- Improved (mutant) nitrile hydratases in which amino acid substitution is performed on wild-type nitrile hydratase are known (JP 2010-172295 A, JP 2007-143409 A, JP 2007-043910 A, etc.) )
- microorganisms introduced with these improved nitrile hydratases can also be used.
- microorganisms having nitrile hydratase activity or processed products thereof can be used not only for the amide synthesis reaction immediately after the preparation of the cells, but also stored after the preparation of the cells and used for the amide synthesis reaction as necessary.
- the method for culturing microorganisms for preparing the cells can be appropriately selected depending on the type of microorganism. You may perform seed
- the cells of microorganisms having nitrile hydratase activity or processed products thereof can be used for batch reactions or can be used for continuous reactions.
- the reaction format can be selected from an appropriate format such as a fluidized bed, a fixed bed, and a suspended bed.
- the catalyst temperature in the reaction solution at that time is not particularly limited as long as the mixing of the aqueous medium and the nitrile compound is not hindered.
- aqueous medium water or a buffer such as phosphate, inorganic salt such as sulfate or carbonate, alkali metal hydroxide, amide compound, nitrile compound, catalyst having nitrile hydratase activity, etc. It refers to an aqueous solution (the whole reaction solution) dissolved at a proper concentration.
- reaction temperature (reaction mixture temperature) in the production method of the present invention is not limited, but is preferably 10 to 40 ° C, more preferably 20 to 35 ° C. If the reaction temperature is 10 ° C. or higher, not only can the reaction activity of the biocatalyst be sufficiently increased, but also the cooling water temperature can be raised, so that a chilled water tower can be used instead of the refrigerator, The cooling energy can be reduced. Moreover, if reaction temperature is 40 degrees C or less, it will be easy to suppress the deactivation of a microbial catalyst.
- the reaction time in the production method of the present invention is not limited, but is preferably 1 to 50 hours, and more preferably 3 to 20 hours, for example.
- the dry cell concentration of the resting cells to be suspended is 4% by mass or more, preferably 5% by mass or more as dry cells.
- the concentration of the cell suspension is 4 to 20% by mass, preferably 5 to 15% by mass, more preferably 5 to 10% by mass, and still more preferably 8% by mass as dry cells.
- the nitrile compound used as a raw material in the production method of the present invention is not particularly limited as long as it is a compound that can be converted into an amide compound by a catalyst having nitrile hydratase activity.
- aliphatic saturated nitriles such as acetonitrile, propionitrile, succinonitrile, adiponitrile
- aliphatic unsaturated nitriles such as acrylonitrile, methacrylonitrile
- aromatic nitriles such as benzonitrile, phthalodinitrile, and nicotinonitrile
- heterocyclic nitriles such as
- the nitrile compound in the present invention is preferably a C2-C4 nitrile compound such as acetonitrile, propionitrile, acrylonitrile, methacrylonitrile, n-butyronitrile, isobutyronitrile, and more preferably acrylonitrile, methacrylonitrile
- nitrile compounds become commercial products through a purification process.
- acrylonitrile is produced industrially by the ammoxidation method of propylene, and cyanic acid is removed together with other by-products by distillation purification after the reaction.
- the product contains hydrocyanic acid that is not removed by this operation.
- it is preferable to reduce the amount of hydrocyanic acid contained in the starting nitrile compound.
- Further reduction of hydrocyanic acid remaining in the nitrile compound used in the present embodiment can be performed by a chemical method.
- a chemical method it is desirable to modify the nitrile compound or to reduce the quality of the produced amide compound, and to avoid the increase of impurities.
- a method using an ion exchange resin a nitrile compound is unsaturated.
- a method of adding hydrocyanic acid to the nitrile compound under alkaline conditions can be mentioned (Patent Documents 4, 5, etc.).
- the removal amount of hydrocyanic acid is preferably as large as possible, and is usually reduced so that the concentration of hydrocyanic acid in the nitrile compound is preferably 1.5 ppm or less, more preferably 0.8 ppm, and even more preferably 0.5 ppm or less.
- the concentration of hydrocyanic acid may be below the detection limit.
- the concentration of hydrocyanic acid contained in acrylonitrile can be determined by a titration method using silver nitrate after extraction with an alkaline solution. Alternatively, it can be measured by absorptiometry.
- acrylonitrile is industrially produced by the ammoxidation method of propylene, but commercially available acrylonitrile contains zinc for the reason that a trace amount of zinc contained in the line is eluted.
- the zinc concentration in the nitrile compound used in the present embodiment may be a concentration that suppresses a decrease in the reaction rate.
- the zinc concentration in the nitrile compound is 0.4 ppm or less, preferably 0.3 ppm or less, More preferably, it is 0.2 ppm, More preferably, it is 0.1 ppm or less.
- Any method may be used for removing zinc from the nitrile compound, for example, distillation, activated carbon, activated alumina, zeolite, silica gel or the like, anion exchange resin, or the like.
- the zinc concentration in acrylonitrile can be measured with an inductively coupled plasma emission spectrometer.
- the zinc concentration in the nitrile compound it is possible to suppress a decrease in the activity of the nitrile hydratase and improve the reaction rate in the amide compound synthesis.
- the effect of reducing zinc can be further enhanced by removing and reducing other organic impurities (for example, benzene, hydrocyanic acid, acrolein, and oxazole) contained in the nitrile compound.
- the above-described removal of zinc and impurities can be achieved by a purification process well known in the art, and can be carried out by various methods such as distillation, alkali treatment, adsorption removal, and anion exchange resin described above.
- An aqueous solution containing an amide compound, particularly an acrylamide compound, obtained by the method of the present invention is a high-grade acrylamide aqueous solution in which the concentration of organic impurities such as zinc and hydrocyanic acid is reduced.
- the acrylamide aqueous solution of the present invention has a zinc concentration of 0.4 ppm or less, preferably 0.3 ppm or less, more preferably 0.2 ppm or less, most preferably 0.1 ppm or less, and more preferably a hydrocyanic acid concentration of 1.5 ppm. Below, preferably 0.8 ppm or less, more preferably 0.5 ppm or less.
- Example 1 (Preparation of bacterial cells) Rhodococcus rhodochrous J-1 (FERMBP-1478) Rhodococcus rhodochros strain J-1 having nitrile hydratase activity [Rhodococcus rhodochrous J-1 (FERMBP-1478)] was used.
- 3L jar fermenter manufactured by Takasugi Seisakusho
- a medium (pH 7.0) 2.5 L prepared by dissolving 0.1% of the product and cobalt chloride 0.01% in tap water was added and sterilized by autoclaving at 121 ° C. for 20 minutes.
- This medium was inoculated with 20 mL of Rhodococcus rhodochrous J-1 and cultured under light shielding at 35 ° C. and 230 rpm for 42 hours. This was washed with a 50 mM phosphate buffer (pH 7.0) to obtain a cell suspension (3% in terms of dry cell).
- Example 2 The same procedure as in Example 1 was performed except that the time for contacting with sodium hydroxide added in Example 1 was adjusted and the concentration of hydrocyanic acid in acrylonitrile was 1.5 ppm. As a result, the reaction rate was 76.0%.
- Example 3 The same procedure as in Example 1 was carried out except that the concentration of hydrocyanic acid in acrylonitrile was 1.5 ppm, the time for passing acrylonitrile through the reactor in Example 1 was adjusted, and the zinc concentration was 0.3 ppm. As a result, the reaction rate was 71.7%.
- Example 4 The experiment was performed in the same manner as in Example 1 except that the concentration of hydrocyanic acid in acrylonitrile was 3.0 ppm and the zinc concentration was 0.3 ppm. As a result, the reaction rate was 42.3%.
- Example 2 The same procedure as in Example 1 was performed except that the hydrocyanic acid concentration in acrylonitrile was 1.5 ppm and the zinc concentration was 0.5 ppm. As a result, the reaction rate was 18.5%.
- Example 3 The same procedure as in Example 1 was performed except that the hydrocyanic acid concentration in acrylonitrile was 2.0 ppm and the zinc concentration was 0.5 ppm. As a result, the reaction rate was 16.3%.
- glucose 15 g / L glucose 15 g / L, yeast extract 1 g / L, glutamate Na 10 g / L, potassium hydrogen phosphate 0.5 g / L, dipotassium hydrogen phosphate 0.5 g / L, magnesium sulfate heptahydrate
- a medium (pH 7.0) 2.5 L prepared by dissolving 5 g / L and cobalt chloride 1 g / L in tap water was added and sterilized by autoclaving at 121 ° C. for 20 minutes. This medium was inoculated with ATCC12673 / psjN-02A, and cultured for 72 hours at 30 ° C. and 230 rpm in the dark.
- Rhodococcus rhodochrous NCIMB41164 strain The nitrile hydratase derived from Rhodococcus rhodochrous NCIMB41164 was prepared and adjusted in the same manner as described in JP-T-2007-512820. Dipotassium hydrogen phosphate 0.7, potassium hydrogen phosphate 0.3, glucose 10.0, peptone 1.0, yeast extract 3.0, magnesium sulfate heptahydrate 0.5, urea 5.0, cobalt chloride
- the cells were grown in Erlenmeyer flasks with 2 L baffles containing 400 ml of medium containing hexahydrate 0.01 and tap water totaling 1 L. The pH of the medium was adjusted to 7.2 and the culture was grown at 28 ° C. for 5 days.
- a catalyst was prepared by adjusting the acrylamide concentration in 100 ml of the reaction solution to 20% and the acrylonitrile concentration to 3%, and diluting the cultured bacterial solution 2.3 times with 50 mM phosphate buffer (pH 7.0). 0.0 ml was added.
- the same procedure as in Example 1 was performed except for the above method. It was 2.13 [%] when the decrease amount of acrylonitrile after 5 hours was measured as a reaction amount. This was 2.47 times the reaction amount of Comparative Example 5.
- Tables 2 and 3 show the results of using Pseudonocardia thermophila JCM3095 and Rhodococcus rhodochrous NCIMB41164 as catalysts.
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Abstract
Description
[1] ニトリルヒドラターゼ活性を有する生体触媒の存在下、ニトリル化合物から対応するアミド化合物を製造する方法において、該ニトリル化合物中の亜鉛濃度が0.4ppm以下、好ましくは0.3mmp以下、より好ましくは0.2ppm以下であることを特徴とする、アミド化合物の製造方法;
[2] ニトリル化合物中の亜鉛濃度が0.1ppm以下であることを特徴とする、[1]に記載のアミド化合物の製造方法;
[3] ニトリル化合物中の青酸濃度が1.5ppm以下、好ましくは1.0ppm、より好ましくは0.8ppm以下であることを特徴とする、[1]又は[2]に記載のアミド化合物の製造方法;
[4] ニトリル化合物中の青酸濃度が0.5ppm以下であることを特徴とする、[3]に記載のアミド化合物の製造方法;
[5] ニトリル化合物が亜鉛及び青酸や他の不純物を低減する精製工程を経たものである、[1]~[4]のいずれかに記載のアミド化合物の製造方法;
[6] 精製工程が、蒸留、アルカリ処理、イオン交換樹脂、吸着除去(活性炭、活性アルミナ、ゼオライト、シリカゲル等の吸着剤による除去)から選ばれる1又は2以上を含むものである、[5]に記載のアミド化合物の製造方法;
[7] ニトリル化合物がアクリロニトリルであり、前記アミド化合物がアクリルアミドである、[1]~[6]のいずれかに記載のアミド化合物の製造方法;
[8] ニトリルヒドラターゼ活性を有する生体触媒がニトリルヒドラターゼ活性を有する動物細胞、植物細胞、細胞小器官、又は微生物の菌体、あるいはそれらの処理物である、[1]~[7]のいずれかに記載のアミド化合物の製造方法;
[9] ニトリルヒドラターゼ活性を有する微生物がロドコッカス属細菌又は大腸菌である、[8]に記載のアミド化合物の製造方法;
[10] ニトリルヒドラターゼ活性を有する生体触媒が、ロドコッカス属細菌又はシュードノカルディア属細菌由来のニトリルヒドラターゼを発現する微生物の菌体である、[8]又は[9]に記載のアミド化合物の製造方法;
[11] ニトリルヒドラターゼ活性を有する生体触媒を、乾燥菌体として4~20質量%、好ましくは、5~15質量%、より好ましくは、5~10質量%、更に好ましくは、8質量%の濃度で存在させる、[1]~[10]のいずれかに記載のアミド化合物の製造方法;
[12] [1]~[11]のいずれかに記載の方法で製造された、亜鉛濃度が0.4ppm以下、好ましくは0.3mmp以下、より好ましくは0.2ppm以下であるアクリルアミド水溶液;
[13] 亜鉛濃度が0.1ppm以下である、[12]記載のアクリルアミド水溶液;
[14] 青酸濃度が1.5ppm以下、好ましくは0.8ppm以下である、[12]又は[13]記載のアクリルアミド水溶液;
[15] 青酸濃度が0.5ppm以下である[12]又は[13]のアクリルアミド水溶液。
(ニトリルヒドラターゼ活性を有する生体触媒)
本発明において、ニトリルヒドラターゼとは、ニトリル化合物を加水分解して、対応するアミド化合物を生成する能力を持つ酵素をいう。ニトリルヒドラターゼ活性を有する生体触媒はニトリルヒドラターゼタンパク質そのものでもよいが、動物細胞、植物細胞、細胞小器官、又は微生物の菌体、及びそれらの処理物でもよい。
本発明の製造方法において原料として使用されるニトリル化合物とは、ニトリルヒドラターゼ活性を有する触媒によりアミド化合物へ変換される化合物であれば特に限定されない。例えばアセトニトリル、プロピオニトリル、サクシノニトリル、アジポニトリルのような脂肪族飽和ニトリル、アクリロニトリル、メタクリロニトリルのような脂肪族不飽和ニトリル、ベンゾニトリル、フタロジニトリルのような芳香族ニトリル及びニコチノニトリルのような複素環式ニトリルが挙げられる。本発明におけるニトリル化合物は、好ましくはアセトニトリル、プロピオニトリル、アクリロニトリル、メタクリロニトリル、n-ブチロニトリル、イソブチロニトリル等のC2~C4 のニトリル化合物であり、特により好ましくは、アクリロニトリル、メタクリロニトリル、アセトニトリルが好適である。
これらニトリル化合物は精製工程を経て市販製品となる。例えば、アクリロニトリルはプロピレンのアンモ酸化法により工業的に生産されており、青酸は他の副生物と共に反応後の蒸留精製による除去操作が行われている。この操作で除去されない青酸が製品中に含まれている。本発明の製造方法においては、原料のニトリル化合物に含まれる青酸の量を低減させることが好ましい。
また、ニトリル化合物中に含まれる微量の不純物の一つとして亜鉛が挙げられる。例えば、アクリロニトリルでは、プロピレンのアンモ酸化法により工業的に製造されているが、ラインに含まれる微量の亜鉛が溶出するなどの理由により、市販のアクリロニトリルには亜鉛が含まれている。
本発明の方法により得られるアミド化合物、特にアクリルアミド化合物を含む水溶液は、亜鉛や、青酸等の有機不純物の濃度が低減された高品位アクリルアミド水溶液である。
(菌体の調製)Rhodococcus rhodochrous J-1(FERMBP-1478)
ニトリルヒドラターゼ活性を有するロドコッカス ロドクロス J-1株[Rhodococcus rhodochrous J-1(FERMBP-1478)]を使用した。3Lジャーファーメンター(高杉製作所製)にグルコース2.0%、ポリペプトン1.0%、グルタミン酸Na1%、リン酸水素カリウム0.2%、リン酸水素二カリウム0.2%、硫酸マグネシウム7水和物0.1%、塩化コバルト0.01%を水道水に溶解して調製した培地(pH7.0)2.5Lを入れ、121℃、20分のオートクレーブにより滅菌した。この培地に、Rhodoccoccus rhodochrous J-1を20mL接種し、遮光下で35℃、230rpm42時間培養した。これを50mMリン酸緩衝液(pH7.0)にて洗浄し、菌体懸濁液(乾燥菌体換算3%)とした。
反応容器に活性炭(内部表面積1000m2/kg)1kgを有する活性炭固定床吸着剤を投入し、反応器へ温度10℃でアクリロニトリルを通過させた。反応器通過後のアクリロニトリルを回収し、誘導結合プラズマ発光分光分析器(サーモフィッシャーサイエンティフィック社製 ICAP577 )で測定したところ、検出下限の0.07ppm以下となった。
使用する工業用アクリロニトリル(青酸5ppm含有)10Lに0.1Mの水酸化ナトリウムを50g添加し十分に攪拌溶解させ30分間放置し、アルカリ処理を行った。その後、1Mのアクリル酸水溶液を10g添加して中和した。この処理によりアクリロニトリル中の青酸濃度は0.5ppmに低減した。なお、アクリロニトリル中の青酸濃度は吸光光度計(DR500001)(HACH社)にて以下のように測定した。
試験管に9.6gの純水とアクリロニトリル0.4gを入れ25℃で30分間静置した。その後、HACH分析キットにあるCyaniVer.3を入れて30秒間ボルテックスしたのち、30秒間静置した。CyaniVer.4を加え10秒間ボルテックスし、CyaniVer.5を加えて2分間ボルテックスした。25℃で30分間静置したのち、吸光度を測定した。
内容積100mlの蓋付ポリケース(新商器材社製)にリン酸緩衝液3.4g、50.5%アクリルアミド93.1g、アクリロニトリル3.0gを加え、30℃に制御しながら攪拌した。これに前述の菌体0.1gを添加し、反応を開始した。6時間後、反応液を採取し、ガスクロマトグラフィー(カラム:PoraPack-PS(Waters社製),1m,210℃,キャリアガス:ヘリウム,検出器:FID)にてアクリロニトリルの濃度を測定した。反応開始前のアクリロニトリル濃度を100%とし、反応後のアクリロニトリル濃度から反応率を求めた。その結果、82.7%のアクリロニトリルがアクリルアミドに変換されていた。
実施例1で添加した水酸化ナトリウムと接触させる時間を調整し、アクリロニトリル中の青酸濃度を1.5ppmとしたこと以外は、実施例1と同様に行った。その結果、反応率は76.0%であった。
アクリロニトリル中の青酸濃度を1.5ppmとし、また実施例1で反応器にアクリロニトリルを通過させる時間を調整し、亜鉛濃度を0.3ppmとしたこと以外は、実施例1と同様に行った。その結果、反応率は71.7%であった。
アクリロニトリル中の青酸濃度を3.0ppmとし、亜鉛濃度を0.3ppmとしたこと以外は、実施例1と同様に実験を行った。その結果、反応率は42.3%であった。
アクリロニトリル中の青酸濃度を0.5ppm、亜鉛濃度が0.5ppmとした以外は実施例1と同様に実験を行った。その結果、反応率は21.8%であった。
アクリロニトリル中の青酸濃度が1.5ppm、亜鉛濃度を0.5ppmとしたこと以外は、実施例1と同様に行った。その結果、反応率は18.5%であった。
アクリロニトリル中の青酸濃度が2.0ppm、亜鉛濃度を0.5ppmとしたこと以外は、実施例1と同様に行った。その結果、反応率は16.3%であった。
(菌体の調整)Pseudonocardia thermophila JCM3095
Pseudonocardia thermophila JCM3095由来のニトリルヒドラターゼ遺伝子を導入した形質転換体には、特開2011-200132号広報に記載のプラスミドpsj-N02Aを、記載の方法と同様にしてATCC12674株に導入した、形質転換体Rhodococcs rhodochrous ATCC12674/psj-N02Aを用いた。500mlの三角フラスコにグルコース15g/L、酵母エキス1g/L、グルタミン酸Na10g/L、リン酸水素カリウム0.5g/L、リン酸水素二カリウム0.5g/L、硫酸マグネシウム7水和物0.5g/L、塩化コバルト1g/Lを水道水にて溶解して調整した培地(pH7.0)2.5Lを入れ、121℃、20分のオートクレーブにより滅菌した。この培地にATCC12674/psjN-02Aを接種し、遮光下で30℃、230rpmで72時間培養した。
実施例1と同様に、アクリロニトリル中の青酸濃度を0.5ppm、亜鉛濃度を検出下限とした。
反応液100ml中のアクリルアミド濃度が20%、アクリロニトリル濃度が3%となるように調整し、培養後の菌液を遠心分離にて10倍に濃縮した触媒を3.5ml添加した。
上記方法以外は実施例1と同様に行った。5時間後のアクリロニトリルの減少量を反応量として測定したところ、1.76[%]であり、これは比較例4の1.27倍であった。
アクリロニトリル中の亜鉛濃度を0.5ppmとした以外は、実施例5と同様に実験を行った。5時間反応後のアクリロニトリルの反応量を測定したところ、1.38[%]であった。
(菌体の調整)Rhodococcus rhodochrous NCIMB41164株
Rhodococcus rhodochrous NCIMB41164株由来のニトリルヒドラターゼは特表2007―512820に記載されている方法と同様に調整して調整した。リン酸水素二カリウム0.7、リン酸水素カリウム0.3、グルコース10.0、ペプトン1.0、酵母エキス3.0、硫酸マグネシウム七水和物0.5、尿素5.0、塩化コバルト六水和物0.01、全体で1Lとなる水道水、を含む400mlの培地を入れた2Lバッフル付きエルレンマイヤーフラスコで増殖させた。培地のpHを7.2に調整し、培養物を28℃で5日間増殖させた。
実施例1と同様に、アクリロニトリル中の青酸濃度を0.5ppm、亜鉛濃度を検出下限とした。
反応液100ml中のアクリルアミド濃度が20%、アクリロニトリル濃度が3%となるように調整し、培養後の菌液を50mMリン酸緩衝液(pH7.0)で2.3倍に希釈した触媒を1.0ml添加した。上記方法以外は実施例1と同様に行った。5時間後のアクリロニトリルの減少量を反応量として測定したところ、2.13[%]であった。これは比較例5の反応量の2.47倍であった。
アクリロニトリル中の亜鉛濃度を5.5ppmとした以外は、実施例6と同様に実験を行った。5時間反応後のアクリロニトリルの減少量は0.86[%]であった。
Claims (15)
- ニトリルヒドラターゼ活性を有する生体触媒の存在下、
ニトリル化合物から対応するアミド化合物を製造する方法において、該ニトリル化合物中の亜鉛濃度が0.4ppm以下であることを特徴とする、
アミド化合物の製造方法。 - ニトリル化合物中の亜鉛濃度が0.1ppm以下であることを特徴とする、請求項1に記載のアミド化合物の製造方法。
- ニトリル化合物中の青酸濃度が1.5ppm以下であることを特徴とする、請求項1又は2に記載のアミド化合物の製造方法。
- ニトリル化合物中の青酸濃度が0.5ppm以下であることを特徴とする、請求項3に記載のアミド化合物の製造方法。
- ニトリル化合物が精製工程を経たものである、請求項1~4のいずれかに記載のアミド化合物の製造方法。
- 精製工程が、蒸留、アルカリ処理、イオン交換樹脂、及び吸着除去から選ばれる1又は2以上を含む、請求項5に記載のアミド化合物の製造方法。
- ニトリル化合物がアクリロニトリルであり、前記アミド化合物がアクリルアミドである、
請求項1~6のいずれかに記載のアミド化合物の製造方法。 - ニトリルヒドラターゼ活性を有する生体触媒がニトリルヒドラターゼ活性を有する動物細胞、植物細胞、細胞小器官、又は微生物の菌体、あるいはそれらの処理物である、請求項1~7のいずれかに記載のアミド化合物の製造方法。
- ニトリルヒドラターゼ活性を有する微生物がロドコッカス属細菌又は大腸菌である、請求項8に記載のアミド化合物の製造方法。
- ニトリルヒドラターゼ活性を有する生体触媒が、ロドコッカス属細菌又はシュードノカルディア属細菌由来のニトリルヒドラターゼを発現する微生物の菌体である、請求項8又は9に記載のアミド化合物の製造方法。
- ニトリルヒドラターゼ活性を有する生体触媒を、乾燥菌体として4~20質量%の濃度で存在させる、請求項1~10のいずれかに記載のアミド化合物の製造方法。
- 請求項1~11のいずれかに記載の方法で製造された、亜鉛濃度が0.4ppm以下であるアクリルアミド水溶液。
- 亜鉛濃度が0.1ppm 以下である、請求項12記載のアクリルアミド水溶液。
- 青酸濃度が1.5ppm以下である、請求項12又は13記載のアクリルアミド水溶液。
- 青酸濃度が0.5ppm以下である、請求項12又は13記載のアクリルアミド水溶液。
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