CN101283102A - Process for producing amide compound - Google Patents
Process for producing amide compound Download PDFInfo
- Publication number
- CN101283102A CN101283102A CNA2006800371804A CN200680037180A CN101283102A CN 101283102 A CN101283102 A CN 101283102A CN A2006800371804 A CNA2006800371804 A CN A2006800371804A CN 200680037180 A CN200680037180 A CN 200680037180A CN 101283102 A CN101283102 A CN 101283102A
- Authority
- CN
- China
- Prior art keywords
- acrylamide
- amide compound
- nitrile
- concentration
- nitrile hydratase
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
Abstract
The present invention provides a method for efficiently producing a corresponding amide compound from a nitrile compound by a reaction using a nitrile hydratase and a method for producing an amide-based polymer excellent in quality from the amide compound. In addition, the present invention provides a method for more efficiently producing an acrylamide with higher quality by a microbial catalyst containing a nitrile hydratase and the like and a method for producing an acrylamide-based polymer, which is excellent in hue, has a good balance between the water solubility and the high molecular weight and is also excellent in quality, by using the acrylamide. The method for producing an amide compound of the present invention is characterized in that in a method for producing an amide compound from a nitrile compound in an aqueous medium in the presence of a catalyst having a nitrile hydratase activity, the concentration of benzene in the aqueous medium is 4.0 ppm or less. In addition, the method for producing an amide-based polymer of the present invention is characterized by homopolymerizing the amide compound or by copolymerizing the amide compound and at least unsaturated monomer copolymerizable with the amide compound. Further, the method for producing acrylamide of the present invention is characterized by hydrating acrylonitrile having a concentration of acrolein of 1 ppm or less by a microbial cell containing a nitrile hydratase or a processed product of the microbial cell in an aqueous medium.; Furthermore, the method for producing an acrylamide-based polymer of the present invention is characterized by homopolymerizing the acrylamide or by copolymerizing the acrylamide and at least one unsaturated monomer copolymerizable with the acrylamide.
Description
Technical field
The present invention relates to the preparation method of amide compound.
The present invention's (first invention) relates to the method for preparing amide compound and acylamide polymer in more detail, more specifically, relate to using and have the active catalyzer of Nitrile hydratase (nitrile hydratase), the method that in aqueous medium, prepares corresponding amide compound effectively, and the method for preparing high-quality acylamide polymer by this amide compound by nitrile compound.In addition, the present invention's (second invention) relates to the method for preparing acrylamide, reaches acrylamide copolymer in more detail, more specifically, the propene hydrate nitriles such as thalline of the microorganism by containing Nitrile hydratase prepare high-quality acrylamide method, and prepare the method for high-quality acrylamide copolymer by this acrylamide.
Background technology
About industrial useful amide compound, various preparation methods are disclosed as described below.
In recent years, found to have the active Nitrile hydratase of nitrile hydration that hydration cyano group is converted into amide group, and disclose the method by the corresponding amide compound of nitrile compound preparation such as the microbial cells that uses this enzyme or have this enzyme.Known this preparation method compares with the existing scientific method, has the transformation efficiency and the selection rate advantages of higher that are converted into corresponding amide compound by nitrile compound.
Utilizing above-mentioned Nitrile hydratase when industrial preparation amide compound, will be important as productivity (molecule number of the amide compound that the 1 molecule Nitrile hydratase produces) maximization of the amide compound of the Nitrile hydratase of catalyzer.Therefore, in order to keep or to improve enzymic activity, suppress active and reduce, improve the enzymic activity that reduced etc., various schemes have been proposed.For example, under the condition of not following cell proliferation, the microbial cells or this bacterial disposing thing that contain Nitrile hydratase are contacted with oxygenant, keeping thus or improving enzymic activity has been known (referring to patent documentation 1).In addition, reduced the nitrile compound of the concentration of contained prussic acid by use, it also is known (referring to patent documentation 2) that the activity that suppresses Nitrile hydratase reduces.In addition, also known following method: the method (referring to patent documentation 3) of using the thalline after glutaraldehyde cross-linking is handled to react; The method of in the presence of higher unsaturated fatty acid or its esters, reacting (referring to patent documentation 4); Thalline or the handled thing method (referring to patent documentation 5) of reacting etc. of use after organic solvent is handled.It more than is the background technology of first invention.
In addition, as mentioned above, as one of main preparation methods of acrylamide, can enumerate the method for vinyl cyanide being carried out hydration reaction, metallic copper catalyzer such as copper carries out the method for hydration reaction or carries out the method for hydration reaction with the microbial cells that contains Nitrile hydratase and this bacterial disposing thing etc. as catalyzer in for example known useful Ruan.
In the aforesaid method, compare with existing method of carrying out hydration reaction as the preparation method of the acrylamide of catalyzer with microbial cells of containing Nitrile hydratase etc. by metallic copper catalyzer etc., because the transformation efficiency and the selection rate height of vinyl cyanide, pretend to industrial preparation method and receive much concern.
In order to be catalyzer with the microbial cells that contains this Nitrile hydratase etc., the more high-quality acrylamide of preparation effectively must remove the impurity of the katalysis of the microbial cells that disinthibites etc. as much as possible.
In addition, the acrylamide that is obtained by this reaction mainly is used as the raw material of acrylamide copolymer, but in recent years, requires this more high-qualityization of acrylamide copolymer.For example, acrylamide copolymer can be used for the agglutinant purposes, but, require keeping the further polymer quantification of water miscible while as the acrylamide copolymer of agglutinant in recent years along with improving performance demands.In addition, acrylamide copolymer can be used to make paper with purposes such as additives,, require the more excellent polymkeric substance of tone for the quality of the further paper of raising gained as this system paper additive.
As mentioned above, method as the quality of the quality of improving the acrylamide that obtains by the thalline catalyzer that contains Nitrile hydratase etc. or polyacrylamide, known have a following method: after reducing prussic acid concentration in the nitrile compound by chemical process, make Nitrile hydratase act on preparation method's (for example, referring to patent documentation 2) of the amide compound of nitrile compound; As contained De oxazole of impurity and prussic acid, vinyl cyanide is converted into acrylamide in the reduction vinyl cyanide, prepares the method (for example, referring to patent documentation 6) of acrylamide copolymer by this acrylamide.It more than is the background technology of second invention.
Patent documentation 1: the spy opens the 2004-350573 communique
Patent documentation 2: the spy opens the 11-123098 communique
Patent documentation 3: the spy opens flat 7-265091 communique
Patent documentation 4: the spy opens flat 7-265090 communique
Patent documentation 5: the spy opens flat 5-308980 communique
Patent documentation 6: the international specification sheets that discloses No. 2004/090148
Summary of the invention
But, when utilizing Nitrile hydratase to prepare amide compound effectively, the phenomenon that exists the amide compound productivity of the insurmountable Nitrile hydratase that is caused by other reasons to reduce in the prior art described in the background technology of first invention has its major cause to be solved.
Therefore, the purpose of first invention is to be provided at the method that is prepared corresponding amide compound in the reaction that utilizes Nitrile hydratase by nitrile compound effectively.Also provide use to prepare the method for high-quality acylamide polymer by the amide compound of method for preparing.
In addition, from the reason of the katalysis of the microbial cells that get rid of to suppress to contain Nitrile hydratase etc., carry out the viewpoint of the hydration reaction of vinyl cyanide effectively, the method described in the background technology of second invention may not necessarily obtain effect of sufficient.From improving acrylamide, and the viewpoint of the quality of acrylamide copolymer, still have room for improvement.
Therefore, the purpose of second invention be with the microbial catalyst etc. that contains Nitrile hydratase more effectively the more high-quality acrylamide of preparation method, and use this acrylamide to obtain the tone excellence, realized the preparation method of the acrylamide copolymer of water-soluble and the excellent quality that polymer quantizes simultaneously.
In order to solve the problem of above-mentioned first invention, the inventor etc. have carried out deep research to the preparation method of amide compound, find to use and have the active catalyzer of Nitrile hydratase, in the method by the corresponding amide compound of nitrile compound preparation in aqueous medium, benzene concentration in the aqueous medium is reduced to below the specific concentrations, can reduce the speed of response of Nitrile hydratase thus and prepare amide compound effectively.Need to prove that the benzene in the aqueous medium derives from the nitrile compound as raw material usually, when sneaking into, also can prepare amide compound effectively by being reduced to identical concentration conditions because of other reasons.In addition, can use the amide compound that under the reaction conditions that suppresses benzene concentration, prepares according to aforesaid method, prepare acylamide polymer, obtain the acylamide polymer of tone excellence thus.
That is, first invention is as described below.
[1] a kind of preparation method of amide compound, described method be have the active catalyzer of Nitrile hydratase in the presence of, in aqueous medium, prepare the method for amide compound by nitrile compound, it is characterized in that the benzene concentration in the aqueous medium is below the 4.0ppm.
[2] as the preparation method of [1] described amide compound, wherein, Nitrile hydratase is to derive from the Nitrile hydratase of Pseudonocardia or from the Nitrile hydratase of Rhod.
[3] as the preparation method of [1] or [2] described amide compound, wherein, nitrile compound is vinyl cyanide or methacrylonitrile.
[4] a kind of method for preparing acylamide polymer, described method are described amide compound of homopolymerization [1] or the described amide compound of copolymerization and can prepare acylamide polymer with at least a unsaturated monomer of amide compound copolymerization.
[5] as [4] the described method for preparing acylamide polymer, wherein, above-mentioned amide compound is acrylamide or Methacrylamide.
In addition, the inventor etc. have studied the problem of above-mentioned second invention, by reducing contained propenal concentration in the vinyl cyanide, can keep the catalytic activity of Nitrile hydratase, and can obtain high-quality acrylamide, and utilize this acrylamide can obtain the tone excellence, can realize acrylamide copolymer water-soluble and that polymer quantizes simultaneously, thereby finished second invention.
That is, the preparation method of acrylamide of second invention is characterised in that, making propenal concentration with the thalline of the microorganism that contains Nitrile hydratase or this bacterial disposing thing is that the following vinyl cyanide of 1ppm carries out hydration reaction in aqueous medium.
The concentration of contained prussic acid is below the 5ppm in the preferred aforesaid propylene nitrile.
In addition, the concentration of contained De oxazole is below the 10ppm in the also preferred aforesaid propylene nitrile.
More preferably the concentration of contained prussic acid is that the concentration of the following, Qie of 5ppm oxazole is below the 10ppm in the aforesaid propylene nitrile.
The preparation method of acrylamide copolymer of second invention is characterised in that homopolymerization aforesaid propylene acid amides, or copolymerization aforesaid propylene acid amides and can with at least a unsaturated monomer of acrylamide copolymerization.
According to first invention, in the reaction that utilizes Nitrile hydratase, be reduced to below the specific concentrations by the benzene concentration in the aqueous medium that will contain nitrile compound, can be effectively by the corresponding amide compound of nitrile compound preparation.In addition, utilize aforesaid method, under the reaction conditions that has suppressed benzene concentration, prepare amide compound, use the amide compound that makes to prepare acylamide polymer, can obtain the acylamide polymer of tone excellence thus.
In addition, according to second invention, utilization contains the microbial catalyst of Nitrile hydratase etc., can prepare more high-quality acrylamide more efficiently.According to second invention, can also obtain the tone excellence, realize the acrylamide copolymer of the excellent quality that water-soluble and polymer quantizes simultaneously.
Embodiment
1. first invention
Below, describe first invention in detail.
What what is called was used for first invention has an active catalyzer of Nitrile hydratase, is meant thalline or this bacterial disposing thing of the microorganism that produces Nitrile hydratase.Said herein Nitrile hydratase is meant the protein of the ability with hydration nitrile compound.As the microorganism that produces Nitrile hydratase, can enumerate Nocardia bacteria (Nocardia) and belong to, rod bacillus (Corynebacterium) belongs to, genus bacillus (Bacillus) belongs to, the thermophilic bacillus, pseudomonas (Pseudomonas) belongs to, micrococci (Micrococcus) belongs to, planting with prunosus red coccus (rhodochrous) is rhodococcus (Rhodococcus) genus of representative, acinetobacter calcoaceticus (Acinetobacter) belongs to, bacillus flavus (Xanthobacter) belongs to, streptomycete (Streptomyces) belongs to, root nodule bacterium (Rhizobium) belong to, klebsiella (Klebsiella) belongs to, enterobacteria (Enterobacter) belongs to, Erwinia (Erwinia) belongs to, Aeromonas (Aeromonas) belongs to, citric acid bacillus (Citrobacter) belongs to, Alcaligenes (Achromobacter) belongs to, edaphic bacillus (Agrobacterium) belongs to or plants with thermophile bacteria (thermophila) is false Nocardia bacteria (Pseudonocardia) genus of representative, sporeless bacterium (Bacteridium) belongs to, the microorganism that tyrothricin (Brevibacterium) belongs to etc.Preferably enumerate the microorganism that belongs to Pseudonocardia or Rhod, preferred especially thermophilic false Nocardia bacteria (Pseudonocardia thermophila) JCM3095 or prunosus red coccus (Rhodococcus rhodochrous) J-1.
In addition, the transformant of expressing in any host by the Nitrile hydratase gene of this microbial cloning is also contained in the microorganism of said generation Nitrile hydratase in first invention.Need to prove, the colon bacillus (Escherichia coli) that said herein any host can enumerate among the following embodiment is typical example, but be not particularly limited in colon bacillus, also comprise subtilis other microorganism strains such as bacillus bacterium, yeast or actinomycetes such as (Bacillus subtilis).As such example, (this bacterial strain is based on Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purposes of Patent Procedure can to enumerate MT-10822, be deposited in the Ibaraki county on February 7th, 1996 and build in the life engineering Industrial Technology Research Institute of Govement Industrial Research Inst., Ministry of Commerce in No. 3,1 section a kind in ripple city east, deposit number is FERM BP-5785).In addition, the transformant of expressing the Nitrile hydratase of following anomaly is also included within the microorganism of said generation Nitrile hydratase in first invention, the Nitrile hydratase of described anomaly is to use recombinant DNA technology, with other amino-acid substitutions or disappearance, elimination or insert 1 of constituting this enzyme or 2, further improve the anomaly Nitrile hydratase of amide compound patience or nitrile compound patience, temperature tolerance with upper amino acid.
When in the preparation method of first invention, using the microorganism that produces above-mentioned Nitrile hydratase, use thalline or the bacterial disposing thing of this microorganism.Thalline can utilize the known general method in molecular biology physiotechnology genetic engineering field to be prepared.For example, can enumerate following method: in common liquid nutrient medium such as LB substratum or M9 substratum behind this microorganism of inoculation, (be generally 20 ℃～50 ℃ in suitable culture temperature, but when being thermophile bacteria, can be for more than 50 ℃) under make its growth, then, by this microorganism of centrifugation, obtain from the nutrient solution Separation and Recovery.
In addition, shape to the bacterial disposing thing of microorganism is not particularly limited, have the Nitrile hydratase active fractions gained of the extract of mentioned microorganism thalline or triturate, this extract of separation and purification or triturate back isolate, use appropriate carriers with the extract triturate of this microbial cells or this thalline after the fixed compound that fixedly obtains of isolate etc., as long as above-mentioned substance has the activity of Nitrile hydratase, just can be as said bacterial disposing thing in first invention.
The microbial cells or this bacterial disposing thing that produce above-mentioned Nitrile hydratase certainly are used for reaction immediately after preparation, also can preserve after preparation, use as required.
Microbial cells or this bacterial disposing thing of the generation Nitrile hydratase in first invention can be used for stepwise reaction, also can be used for successive reaction.In addition, reaction formation can be selected suitable forms such as outstanding turbid bed, fixed bed, fluidized-bed according to the thalline of microorganism or the form of bacterial disposing thing.This catalyst concn in the reaction solution is not particularly limited as long as do not hinder the mixing of aqueous medium and nitrile compound at this moment.
Aqueous medium in first invention be meant water or with suitable inorganic salt such as buffer reagent, vitriol or carbonate such as concentration dissolved phosphorus hydrochlorate, alkali-metal oxyhydroxide, amide compound, nitrile compound, have the aqueous solution (reaction solution integral body) that the active catalyzer of Nitrile hydratase etc. obtains.In first invention, be in homogeneous system in the saturation concentration with respect to the aqueous solution, or be in the above nitrile of saturation concentration mutually and two phase systems of water, all this solution integral body is defined as aqueous medium no matter this solution is nitrile compound.Need to prove, in this specification sheets, the aqueous medium in first invention is also referred to as " aqueous medium (I) ".During two phase systems, use the rotation wing or line mixer suitable mixing devices such as (line mixer), thorough mixing also is important leaving standstill the water that is separated into two-phase down with nitrile mutually.
In first invention, the nitrile compound concentration in the aqueous medium during reaction (I) is so long as not because of the benzene concentration in the aqueous medium (I) causes scope that speed of response reduces or Nitrile hydratase not because of the scope of nitrile compound inactivation gets final product, be not particularly limited.The weight % of preferred nitrile compound is below the 50 weight %.
Used nitrile compound is so long as in aqueous medium (I) in first invention, and the compound that is converted into amide compound under the effect with the active catalyzer of Nitrile hydratase gets final product, and is not particularly limited.Preferably enumerate carbonatomss such as acetonitrile, propionitrile, vinyl cyanide, methacrylonitrile, n-Butyronitrile, isopropyl cyanide, crotononitrile, Alpha-hydroxy isopropyl cyanide and be 2～4 nitrile compound typical example as this nitrile compound.More preferably use vinyl cyanide, methacrylonitrile.
Above-mentioned nitrile compound is made the commercially available prod through refining step, but contains trace impurity.As one of impurity, can enumerate benzene, for example vinyl cyanide utilizes the oxidation proceses of ammonia of propylene to carry out industrial preparation, but owing to micro-benzene contained in the propylene is brought into the medium reason of vinyl cyanide product, causes containing benzene in the commercially available vinyl cyanide product.
Contained benzene concentration in the aqueous medium (I) is so long as the concentration that inhibited reaction speed reduces gets final product, and being generally 4.0 is below the m, is preferably below the 2.2ppm.Herein, it is that speed of response in the following reaction of 2.2ppm is 100% that the scope that inhibited reaction speed reduces is meant with benzene concentration contained in the aqueous medium (I), and relative response speed is the scope more than 80%.In addition, contained benzene concentration is to be meant below the 4.0ppm that the amount of contained benzene in the 1kg aqueous medium (I) is below the 4mg in the aqueous medium (I).The method of removing the method for benzene or removing benzene from nitrile compound from aqueous medium (I) can be any means, for example distillation, carries out adsorption treatment, utilizes solid acids such as heteropolyacid as super acids to carry out adsorption treatment, handle, extract, carry out biological decomposition, utilize the volatility of benzene to outgas to handle etc. with the microorganism that can assimilate benzene with tetramethylene sulfone with column chromatography with gac.
Reaction in first invention is carried out under normal pressure usually, in order to improve the solubleness of acrylic compounds in aqueous medium (I), can react adding to depress.In addition, temperature of reaction is not particularly limited, preferably in the temperature range of this Nitrile hydratase non-inactivation, more preferably 0～50 ℃.On the other hand, pH is not particularly limited, preferably in the scope of pH5～pH10 so long as can keep that Nitrile hydratase is active to get final product.
Amide compound or the copolyamide compound that the acylamide polymer of first invention can make as described above by homopolymerization and being prepared with at least a unsaturated monomer of amide compound copolymerization.Herein, amide compound is preferably acrylamide or the Methacrylamide that the preparation method of amide compound that utilizes first invention obtains.
As can with the unsaturated monomer of amide compound copolymerization, can enumerate unsaturated carboxylic acid and their salt such as vinylformic acid, methacrylic acid, methylene-succinic acid, toxilic acid, fumaric acid;
Vinyl sulfonic acid, styrene sulfonic acid, acrylamide methyl propane sulfonic acid and their salt;
Methacrylic acid N, N-dimethylamino ethyl ester, methacrylic acid N, N-diethylamino ethyl ester, vinylformic acid N, (methyl) acrylic acid alkylaminoalkyl or their quaternary ammonium derivatives such as N-dimethylamino ethyl ester;
N such as (N, N-dimethylaminopropyl) Methacrylamide, (N, N-dimethylaminopropyl) acrylamide, N-dialkyl aminoalkyl (methyl) acrylamide or their quaternary ammonium derivative;
Acetone acrylamide, N,N-DMAA, (N, N-dimethyl) Methacrylamide, (N-ethyl) Methacrylamide, N-ethyl acrylamide, N, wetting ability acrylamides such as N-diethyl acrylamide, N-propyl group acrylamide;
N-acryl tetramethyleneimine, N-acryl piperidines, N-acryloyl morpholine; Hydroxyethyl methylacrylate, Hydroxyethyl acrylate, Rocryl 410, Propylene glycol monoacrylate;
Methoxy poly (ethylene glycol) (methyl) acrylate, N-vinyl-2-Pyrrolidone; Methacrylamide;
N, N-alkyl (methyl) acrylamide derivatives such as N-two-n-propyl acrylamide, N-normal-butyl acrylamide, N-n-hexyl acrylamide, (N-n-hexyl) Methacrylamide, N-n-octyl acrylamide, (N-n-octyl) Methacrylamide, uncle's N-octyl acrylamide, N-dodecyl acrylamide, (N-dodecyl) Methacrylamide;
N, N-(ω-glycidoxyalkyl) (methyl) acrylamide derivatives such as N-diglycidyl acrylamide, (N, N-diglycidyl) Methacrylamide, N-(4-glycidoxy butyl) acrylamide, N-(4-glycidoxy butyl) Methacrylamide, N-(5-glycidoxy amyl group) acrylamide, N-(6-glycidoxy hexyl) acrylamide;
(methyl) acrylate derivatives such as (methyl) methyl acrylate, (methyl) ethyl propenoate, (methyl) butyl acrylate, (methyl) vinylformic acid Lauryl Ester, (methyl) 2-EHA, (methyl) vinylformic acid glycidyl esters;
Olefines such as vinyl cyanide, methacrylonitrile, vinyl-acetic ester, vinylchlorid, vinylidene chloride, ethene, propylene, butylene, vinylbenzene, alpha-methyl styrene, divinyl, isoprene etc.
Above-mentioned monomer can be used alone or two or more kinds may be used.
As above-mentioned monomeric polymerization process, aqueous solution polymerization, letex polymerization etc. are for example arranged.
In the above-mentioned polymerization process, when adopting aqueous solution polymerization, amide compound is 5～90 weight % with the total concn of the unsaturated monomer that adds as required usually.
As polymerization starter, for example can use radical polymerization initiator.
As radical polymerization initiator, can enumerate superoxide such as Potassium Persulphate, ammonium persulphate, hydrogen peroxide, benzoyl peroxide; Diisopropyl azodicarboxylate, 2,2 '-azo two (4-amidine propane), 2 hydrochlorides, 4,4 '-azo two azo class free-radical initiators such as (4-cyanopentanoic acid sodium); And with the so-called redox class catalyzer of reductive agents such as above-mentioned superoxide and sodium bisulfite, trolamine, ferrous ammonium sulphate.
Above-mentioned polymerization starter can be used alone or two or more kinds may be used.The amount of polymerization starter is being in the scope of 0.001～5 weight % with respect to monomeric gross weight usually.
During for single polymerization starter, polymerization temperature is usually in 0～120 ℃ scope, more preferably in 5～90 ℃ scope.In addition, polymerization temperature need not the temperature that always keeps certain, can follow polymeric suitably to change, and follows polymeric to carry out usually, produces heat of polymerization, and polymerization temperature has the tendency of rising, so cool off as required sometimes.
Atmosphere during polymerization is not particularly limited, and from carrying out the polymeric viewpoint rapidly, for example preferably carries out polymerization in atmosphere of inert gases such as nitrogen.
Polymerization time is not particularly limited, usually in 1～20 hour scope.
In addition, the pH of the aqueous solution also is not particularly limited during polymerization, can regulate pH as required and carry out polymerization.As the pH regulator agent that can use this moment, can enumerate alkali such as sodium hydroxide, potassium hydroxide, ammonia; Mineral acids such as phosphoric acid, sulfuric acid, hydrochloric acid; Organic acid such as formic acid, acetate etc.
Utilize the molecular weight of the polymkeric substance of the first invention gained to be not particularly limited, usually in 100,000～5,000 ten thousand scope, preferably in 500,000～3,000 ten thousand scope.
The acylamide polymer of first invention that obtains thus is to realize polymkeric substance water-soluble and that polymer quantizes simultaneously, and tone is also excellent, can be preferably used as agglutinant, system paper additive, oil recovery agent etc.
2. second invention
Below, describe second invention in detail.
The acrylamide preparation method's who is used for second invention raw material at first, is described.
(vinyl cyanide)
In second invention, use the concentration of propenal to be the vinyl cyanide below the 1ppm.Herein, the concentration of propenal is that the following vinyl cyanide of 1ppm is meant that the amount of propenal contained in the vinyl cyanide that 1kg uses as the raw material of second invention is as below the 1mg.
The method that the concentration of propenal contained in the vinyl cyanide is set at below the 1ppm can be enumerated following method: make the acrolein reaction in methyl ethyl diketone etc. and the vinyl cyanide, by distillation etc., the method for separating this resultant of reaction and vinyl cyanide; Make vinyl cyanide with contain primary amino and/or secondary amino group in return the porous ion exchange resin of group contact the method for removing the propenal in the vinyl cyanide; Make vinyl cyanide contact the aldehydes that reduces in the vinyl cyanide, the method that is essentially propenal with gel-type weak-base ion-exchange resin with primary amino and/or secondary amino group functional group.
The concentration of contained propenal can be carried out quantitatively with vapor-phase chromatography, high performance liquid chromatography etc. in the vinyl cyanide.
In second invention, the concentration of the propenal in the raw material propylene nitrile is below the 1ppm, more preferably is below the 0.5ppm.
The concentration of propenal is in above-mentioned scope the time, propenal is to the katalysis of the Nitrile hydratase inhibition that do not react, and use the acrylamide of gained, can obtain the tone excellence, realize the acrylamide copolymer water-soluble and excellent quality that polymer quantizes simultaneously.
The concentration that is used for the contained propenal of second vinyl cyanide of inventing is below the 1ppm, and more preferably the concentration of contained prussic acid is below the 5ppm in this vinyl cyanide.
Herein, the concentration of contained prussic acid is to be meant below the 5ppm that the amount that 1kg is used as prussic acid contained in the vinyl cyanide of raw material of second invention is below the 5mg in the vinyl cyanide.
The concentration of prussic acid contained in the vinyl cyanide is set at method below the 1ppm, for example can enumerates following method: the spy open put down in writing in the flat 11-123098 communique prussic acid is made the method that metal complex is removed; Make the method for spent ion exchange resin; Under alkaline condition to method of vinyl cyanide addition prussic acid etc.
In addition, the concentration of contained prussic acid can be obtained by the volumetry of using Silver Nitrate after extracting with alkaline solution in the vinyl cyanide.
In second invention, the concentration of the prussic acid in the vinyl cyanide is preferably below the 5ppm, more preferably is below the 3ppm, more preferably below the 1ppm.
And, in second invention, the also preferred concentration of removing the contained propenal of vinyl cyanide be below the 1ppm, the concentration of contained De oxazole is below the 10ppm in the vinyl cyanide.
Herein, the concentration of contained De oxazole is to be meant below the 10ppm that the amount that 1kg is used as contained De oxazole in the vinyl cyanide of raw material of second invention is below the 10mg in the vinyl cyanide.
Make the method for concentration below 10ppm of contained De oxazole in the vinyl cyanide, for example can enumerate the method that vinyl cyanide Zhong De oxazole is contacted with the Zeo-karb of H type that the spy opens clear 63-118305 communique record.
In addition, the concentration of contained De oxazole can be carried out quantitatively with vapor-phase chromatography, high performance liquid chromatography etc. in the vinyl cyanide.
In second invention, the concentration of vinyl cyanide Zhong De oxazole is preferably below the 10ppm, more preferably is below the 5ppm, more preferably below the 1ppm.
In addition, in second invention, the concentration that is used for the contained propenal of second vinyl cyanide of inventing is in above-mentioned scope, the concentration of prussic acid is below the 5ppm, be preferably below the 3ppm, more preferably the concentration for the following ， Qie of 1ppm oxazole is below the 10ppm, being preferably below the 5ppm, more preferably is below the 1ppm.
(containing the microbial cells of Nitrile hydratase etc.)
In second invention, can be raw material with above-mentioned vinyl cyanide, be that catalyzer carries out hydration reaction with the microbial cells that contains Nitrile hydratase and bacterial disposing thing thereof etc., obtains the acrylamide of second invention.
In second invention, Nitrile hydratase is meant to have the enzyme that the hydrolysis nitrile compound generates corresponding amide compound ability.Herein, as the microorganism that contains Nitrile hydratase,, be not particularly limited so long as produce the Nitrile hydratase of ability and in acrylamide solution, keep the active microorganism of Nitrile hydratase to get final product with the corresponding amide compound of hydrolysis nitrile compound generation.
Particularly, can enumerate Nocardia bacteria (Nocardia) belongs to, rod bacillus (Corynebacterium) belongs to, genus bacillus (Bacillus) belongs to, the thermophilic bacillus, pseudomonas (Pseudomonas) belongs to, micrococci (Micrococcus) belongs to, planting with prunosus red coccus (rhodochrous) is rhodococcus (Rhodococcus) genus of representative, acinetobacter calcoaceticus (Acinetobacter) belongs to, bacillus flavus (Xanthobacter) belongs to, streptomycete (Streptomyces) belongs to, root nodule bacterium (Rhizobium) belong to, klebsiella (Klebsiella) belongs to, enterobacteria (Enterobacter) belongs to, Erwinia (Erwinia) belongs to, Aeromonas (Aeromonas) belongs to, citric acid bacillus (Citrobacter) belongs to, Alcaligenes (Achromobacter) belongs to, edaphic bacillus (Agrobacterium) belongs to or plants with thermophile bacteria (thermophila) be that the microorganism of false Nocardia bacteria (Pseudonocardia) genus of representative is as preference.
In addition, expressing transformant by the Nitrile hydratase gene of this microbial cloning in any host is also included within second invention in the said microorganism.Need to prove, said herein any host can enumerate the colon bacillus of using among the following embodiment (Escherichiacoli) and be typical example, but be not particularly limited in colon bacillus, also comprise subtilis other microorganism strains such as bacillus bacterium, yeast or actinomycetes such as (Bacillus subtilis).As such example, (this bacterial strain is based on Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purposes of Patent Procedure can to enumerate MT-10822, be deposited in the Ibaraki county on February 7th, 1996 and build in the life engineering Industrial Technology Research Institute of Govement Industrial Research Inst., Ministry of Commerce in No. 3,1 section a kind in ripple city east, deposit number is FERM BP-5785).In addition, the transformant of expressing the Nitrile hydratase of following anomaly is also included within second invention in the said microorganism, the Nitrile hydratase of described anomaly is to use recombinant DNA technology, with other amino-acid substitutions or disappearance, elimination or insert 1 of constituting this enzyme or 2, further improve the anomaly Nitrile hydratase of acrylamide patience or vinyl cyanide patience, temperature tolerance with upper amino acid.
When using mentioned microorganism to prepare amide compound, use thalline or the bacterial disposing thing of this microorganism usually.Thalline can utilize molecular biology, physiotechnology, the known general method in genetic engineering field to be prepared.For example, can enumerate following method: in common liquid nutrient medium such as LB substratum or M9 substratum behind this microorganism of inoculation, (be generally 20 ℃～50 ℃ in suitable culture temperature, but when being thermophile bacteria, can be for more than 50 ℃) under make its growth, then, by this microorganism of centrifugation, separate, reclaim and obtain from nutrient solution.
In addition, the bacterial disposing thing of microorganism of second invention be meant the Nitrile hydratase active fraction gained of the extract of mentioned microorganism thalline or triturate, this extract of separation and purification or triturate back isolate, use fixed compound that appropriate carriers fixedly obtains extract, triturate, the back isolate of this microbial cells or this thalline etc., as long as above-mentioned bacterial disposing thing has the activity of Nitrile hydratase, just can be as said bacterial disposing thing in second invention.This material can use single kind, also can be simultaneously or be used alternatingly the material of the different shape more than 2 kinds.
(aqueous medium)
In addition, the aqueous medium in second invention is meant the water or the aqueous solution that obtains with inorganic salt such as buffer reagent, vitriol or carbonate such as proper concn dissolved phosphorus hydrochlorate, alkali-metal oxyhydroxide or amide compound etc.Need to prove, in this specification sheets, the aqueous medium in second invention is called " aqueous medium (II) ".
(reaction conditions)
In second invention, the concentration of the vinyl cyanide in the aqueous medium (II) is the concentration more than the saturation concentration of this nitrile compound when the reaction beginning.The upper limit of this concentration is not particularly limited, but when supplying with nitrile compound too much, in order to finish reaction, the heat exchanger etc. that needs a large amount of catalyzer and have the reaction vessel of ultra-large volume and be used for the super large of heat extraction, the economical load aspect equipment increases the weight of.Therefore, supply concentration as vinyl cyanide, theoretical Generation Liquid concentration is in acrylamide in the scope of 40～80 weight % and supplies with when all being converted into corresponding acrylamide by this vinyl cyanide, more particularly, be in the scope of 0.4～1.5 weight part with respect to 1 weight parts water vinyl cyanide.
In addition, the reaction times of above-mentioned reaction is also depended on conditions such as catalyzer usage quantity or temperature, usually in 1～80 hour scope, preferably in 2～40 hours scope.
Reaction formation is not particularly limited, and can be multiple step format, half multiple step format, also can carry out the reaction of continous way.In addition, can be in outstanding turbid bed, fixed bed, the moving-bed etc. any, more preferably in having the tank reactor of agitator, plug flow reactor, react usually, can also make up the reactor of various ways.
Catalyst consumption also depends on the kind and the form thereof of reaction conditions or catalyzer, is converted into the dry thalline weight of this microorganism usually, is 10～50000ppm with respect to the weight of reaction solution, is preferably 50～30000ppm.
Hydration reaction is usually at normal pressure or approach to carry out under the normal pressure, for improve nitrile compound in aqueous medium (II) solubleness and carry out adding to depress.In addition, temperature of reaction is preferably carried out in 0～50 ℃ scope, more preferably in 10～40 ℃ scope usually as long as above freezing at aqueous medium (II) is not particularly limited.Also can separate out under the slurry form that in reaction solution, forms and react at resultant.As long as it is active that the pH of the reaction solution during above-mentioned hydration reaction keeps Nitrile hydratase, be not particularly limited, preferably in the scope of pH6～10, more preferably in the scope of pH7～9.
In addition, also can be by the site specific variation active amino-acid substitution body of Nitrile hydratase that is maintained, but based on specific change point and by the kind of metathetical base, construct recombinant plasmid with the method beyond the site specific variation, it is imported host cell, also can obtain identical result.
For example, with synthetic DNA fragments such as DNA synthesizers, the base sequence that described dna fragmentation has a DNA in the zone that is equivalent to change point becomes the base sequence of the sequence behind the amino-acid substitution, with the dna fragmentation that obtains with in advance with this segmental regional replacement that is equivalent to of the isolating pPT-DB1 of additive method, can obtain the target recombinant plasmid.
(preparation of acrylamide copolymer)
Acrylamide or the co-polypropylene acid amides that the acrylamide copolymer of second invention can make as described above by homopolymerization and preparing with at least a unsaturated monomer of acrylamide copolymerization.
As can with the unsaturated monomer of acrylamide copolymerization, can enumerate unsaturated carboxylic acid and their salt such as vinylformic acid, methacrylic acid, methylene-succinic acid, toxilic acid, fumaric acid;
Vinyl sulfonic acid, styrene sulfonic acid, acrylamide methyl propane sulfonic acid and their salt;
Methacrylic acid N, N-dimethylamino ethyl ester, methacrylic acid N, N-diethylamino ethyl ester, vinylformic acid N, (methyl) acrylic acid alkylaminoalkyl or their quaternary ammonium derivatives such as N-dimethylamino ethyl ester;
(N, N-dimethylaminopropyl) Methacrylamide, N, N such as N-dimethylaminopropyl acrylamide, N-dialkyl aminoalkyl (methyl) acrylamide or their quaternary ammonium derivative;
Acetone acrylamide, N,N-DMAA, (N, N-dimethyl) Methacrylamide, (N-ethyl) Methacrylamide, N-ethyl acrylamide, N, wetting ability acrylamides such as N-diethyl acrylamide, N-propyl group acrylamide;
N-acryl tetramethyleneimine, N-acryl piperidines, N-acryloyl morpholine;
Hydroxyethyl methylacrylate, Hydroxyethyl acrylate, Rocryl 410, Propylene glycol monoacrylate;
Methoxy poly (ethylene glycol) (methyl) acrylate, N-vinyl-2-Pyrrolidone; Methacrylamide;
N, N-alkyl (methyl) acrylamide derivatives such as N-two-n-propyl acrylamide, N-normal-butyl acrylamide, N-n-hexyl acrylamide, (N-n-hexyl) Methacrylamide, N-n-octyl acrylamide, (N-n-octyl) Methacrylamide, uncle's N-octyl acrylamide, N-dodecyl acrylamide, (N-dodecyl) Methacrylamide;
N, N-diglycidyl acrylamide, N, N-(ω-glycidoxyalkyl) (methyl) acrylamide derivatives such as N-diglycidyl Methacrylamide, N-(4-glycidoxy butyl) acrylamide, N-(4-glycidoxy butyl) Methacrylamide, N-(5-glycidoxy amyl group) acrylamide, N-(6-glycidoxy hexyl) acrylamide;
(methyl) acrylate derivatives such as (methyl) methyl acrylate, (methyl) ethyl propenoate, (methyl) butyl acrylate, (methyl) vinylformic acid Lauryl Ester, (methyl) 2-EHA, (methyl) vinylformic acid glycidyl esters;
Olefines such as vinyl cyanide, methacrylonitrile, vinyl-acetic ester, vinylchlorid, vinylidene chloride, ethene, propylene, butylene, vinylbenzene, alpha-methyl styrene, divinyl, isoprene etc.
Above-mentioned monomer can be used alone or two or more kinds may be used.
As above-mentioned monomeric polymerization process, aqueous solution polymerization, letex polymerization etc. are for example arranged.
In the above-mentioned polymerization process, when adopting aqueous solution polymerization, acrylamide is 5～90 weight % with the total concn of the unsaturated monomer that adds as required usually.
As polymerization starter, for example can use radical polymerization initiator.
As radical polymerization initiator, can enumerate superoxide such as Potassium Persulphate, ammonium persulphate, hydrogen peroxide, benzoyl peroxide; Diisopropyl azodicarboxylate, 2,2 '-azo two (4-amidine propane), 2 hydrochlorides, 4,4 '-azo two azo class free-radical initiators such as (4-cyanopentanoic acid sodium); And the so-called redox class catalyzer that obtains with reductive agents such as above-mentioned superoxide and sodium bisulfite, trolamine, ferrous ammonium sulphates.
Above-mentioned polymerization starter can be used alone or two or more kinds may be used.The amount of polymerization starter usually with respect to monomeric gross weight in the scope of 0.001～5 weight %.
During for single polymerization starter, polymerization temperature is usually in 0～120 ℃ scope, more preferably in 5～90 ℃ scope.In addition, polymerization temperature need not to remain on certain temperature always, can follow polymeric to carry out appropriate change, usually, follows polymeric to carry out, and produces heat of polymerization, and polymerization temperature has the tendency of rising, so cool off as required sometimes.
Atmosphere during polymerization is not particularly limited, from carrying out polymeric viewpoint, for example preferably polymerization in inert gas atmospheres such as nitrogen fast.
Polymerization time is not particularly limited, usually in 1～20 hour scope.
In addition, the pH of the aqueous solution during polymerization also is not particularly limited, and can regulate pH as required and carry out polymerization.As the pH regulator agent that can use this moment, can enumerate alkali such as sodium hydroxide, potassium hydroxide, ammonia; Mineral acids such as phosphoric acid, sulfuric acid, hydrochloric acid; Organic acid such as formic acid, acetate etc.
The molecular weight of the polymkeric substance of the second invention gained is not particularly limited, usually in 100,000～5,000 ten thousand scope, preferably in 500,000～3,000 ten thousand scope.
The acrylamide copolymer of second invention that obtains thus is to realize polymkeric substance water-soluble and that polymer quantizes simultaneously, and has excellent tone, is preferably used as agglutinant, system paper additive, oil recovery agent etc.
[embodiment]
Below, be described more specifically the present invention based on embodiment, but the present invention is not limited to these embodiment.
1. first inventive embodiment
Need to prove, utilize gas chromatographic analysis to measure benzene concentration.Use the measuring column of the chemical substance evaluation study G-950 1.2mm * 40m of mechanism (25 μ m), use the He carrier gas, utilize fid detector to detect as gas chromatographic analysis.
In addition, during the HPLC in each embodiment and the comparative example analyzed, the Finepak SIL C18-5 (250 * 4.6 φ mm) that uses Japanese beam split system used and contains the 10mM phosphate aqueous solution of 4 volume % acetonitriles as developping solution as post.In addition, acrylamide, Methacrylamide detect by the absorbancy of 220nm.
[preparation example 1-1]
In reaction vessel, pack into have the 1kg gac activated carbon and fixed bed sorbent material of (interior surface area is 1000m2/kg).Under the condition of 10 ℃ of temperature, flow velocity 200m/hr, making benzene concentration with pump is that the vinyl cyanide a of 26ppm passes through sorbent material upward from the below.Benzene concentration in this vinyl cyanide after mensuration is passed through, the result is that benzene concentration is 4.0ppm.Below, the vinyl cyanide after the charcoal absorption processing is called vinyl cyanide b.
[preparation example 1-2]
Directly use the vinyl cyanide c of the concentration of contained benzene as 11ppm.
[preparation example 1-3]
Directly use the methacrylonitrile of the concentration of contained benzene as 8ppm.
The modulation of thalline
[modulating routine 1-1]
Cultivation contains the microorganism from the Nitrile hydratase of thermophilic false Nocardia bacteria JCM3095
Have modulation 100ml substratum in the Erlenmeyer flask of baffle plate (baffle) at 500ml, this substratum has substratum and forms the composition shown in the 1-1, under 121 ℃ with autoclave sterilization 20 minutes after, adding the Ampicillin Trihydrate is 50 μ g/ml until final concentration, prepares 30 bottles altogether.The MT-10822 strain (FERM BP-5785) of inoculation one platinum loop in each baffled Erlenmeyer flask was respectively cultivated 20 hours under the condition of 37 ℃ of 130rpm.After merging the nutrient solution in each baffled Erlenmeyer flask, by centrifugation (15000G * 15 minute), by only isolating thalline in the nutrient solution, then, after being suspended in this thalline in the 50ml physiological saline once more, carry out centrifugation once more, obtain wet thallus.
[substratum is formed 1-1]
5.0g/L yeast extract
10.0g/L poly-peptone
5.0g/L NaCl
10.0mg/L cobalt chloride hexahydrate
40.0mg/L ferric sulfate heptahydrate
pH7.5
[modulating routine 1-2]
Cultivation contains the microorganism of the Nitrile hydratase that derives from prunosus red coccus J-1 strain
The prunosus red coccus J-1 strain of using special fair 06-55148 number record is (as FERMBP-1478, the microbial preservation budapest treaty that is used for patented procedure based on international recognition, be deposited in above-mentioned preservation mechanism, the public can file a request to this mechanism and obtain this bacterial classification), obtain wet thallus.
Modulation 100ml substratum in the baffled Erlenmeyer flask of 500ml, this substratum has substratum and forms the composition shown in the 1-2, sterilizes 20 minutes with autoclave under 121 ℃.The prunosus red coccus J-1 strain that special fair 06-55148 number of inoculation one platinum loop is put down in writing on this substratum is (as FERM BP-1478, be used for the microbial preservation budapest treaty of patented procedure based on international recognition and be deposited in described preservation mechanism, the public can file a request and obtains this bacterial classification to this mechanism), under 30 ℃ of 130rpm, cultivated 72 hours.By centrifugation (15000G * 15 minute) separating thallus only from this nutrient solution, then that this thalline is outstanding once more turbid behind 50ml physiological saline, carry out centrifugation once more, obtain wet thallus.
[substratum is formed 1-2]
10.0g/L glucose
0.5g/L potassium primary phosphate
0.5g/L potassium phosphate,monobasic
0.5g/L magnesium sulfate 7 hydrate
1.0g/L yeast extract
7.5g/L peptone
7.5g/L urea
10.0mg/L cobalt chloride hexahydrate
pH7.2
[embodiment 1-1]
Nitrile compound is converted into amide compound (1)
Suitably diluting the wet thallus of gained among the routine 1-1 of modulation with 20mM-TrisHCl damping fluid (pH7.5), to wherein adding the vinyl cyanide b described in the preparation example 1-1, is 20 weight % until the acrylonitrile concentration of reaction solution integral body, makes it 20 ℃ of reactions 10 minutes down.At this moment, the benzene concentration in the aqueous medium (I) (reaction solution integral body) is 0.8ppm.After the reaction, the 1M phosphate aqueous solution of interpolation and its equivalent in reaction solution, stopped reaction is with the acrylamide concentration of HPLC assay determination generation.Then, calculate the formation speed (=speed of response) of the per unit wet thallus and the acrylamide in unit reaction times.The results are shown in table 1-1.Speed of response with gained is 100%, compares with embodiment 1-2 and embodiment 1-3, comparative example 1-1, comparative example 1-2.
[embodiment 1-2]
Nitrile compound is converted into amide compound (2)
Suitably dilute the wet thallus of modulating gained among the routine 1-1 with 20mM-TrisHCl damping fluid (pH7.5),, it was reacted 10 minutes at 20 ℃ down to wherein adding vinyl cyanide c to the 20 weight % described in the preparation example 1-2.At this moment, the benzene concentration in the aqueous medium (I) is 2.2ppm.Operate in the same manner with embodiment 1-1 afterwards.The results are shown in table 1-1.
[embodiment 1-3]
Nitrile compound is converted into amide compound (3)
Add benzene in the described vinyl cyanide b of preparation example 1-1, the benzene concentration of modulating in vinyl cyanide is 20ppm.Used vinyl cyanide is replaced with this vinyl cyanide, operate in the same manner with embodiment 1-1.At this moment, the benzene concentration in the aqueous medium (I) is 4.0ppm.The results are shown in table 1-1.
[comparative example 1-1]
Nitrile compound is converted into amide compound (1)
Used vinyl cyanide is replaced with the described vinyl cyanide a of preparation example 1-1, operate in the same manner with embodiment 1-1.At this moment, the benzene concentration in the aqueous medium (I) is 5.2ppm.The results are shown in table 1-1.
[comparative example 1-2]
Nitrile compound is converted into amide compound (2)
Add benzene in the described vinyl cyanide b of preparation example 1-1, the benzene concentration of modulating in vinyl cyanide is 26ppm.Used vinyl cyanide is replaced with this vinyl cyanide, operate in the same manner with embodiment 1-1.At this moment, the benzene concentration of aqueous medium (I) is 5.2ppm.The results are shown in table 1-1.
By table 1-1 as can be known, by the benzene concentration in the aqueous medium (I) is set in below the 4.0ppm, reduction that can inhibited reaction speed, and the reason material that causes speed of response to reduce is a benzene.
[embodiment 1-4]
Nitrile compound is converted into amide compound (4)
Used wet thallus is replaced with the wet thallus of modulating routine 1-2 gained, operate in the same manner with embodiment 1-1.The results are shown in table 1-2.Speed of response with gained is 100%, compares with embodiment 1-5, comparative example 1-3.
[embodiment 1-5]
Nitrile compound is converted into amide compound (5)
Used wet thallus is replaced with the wet thallus of modulating routine 1-2 gained, operate in the same manner with embodiment 1-3.The results are shown in table 1-2.
[comparative example 1-3]
Nitrile compound is converted into amide compound (3)
Used wet thallus is replaced with the wet thallus of modulating gained among the routine 1-2, and 1-1 operates in the same manner with comparative example.The results are shown in table 1-2.
[embodiment 1-6]
Nitrile compound is converted into amide compound (6)
Suitably dilute the wet thallus of modulating gained among the routine 1-1 with 20mM-TrisHCl damping fluid (pH7.5),, it was reacted 10 minutes at 20 ℃ down to wherein adding methacrylonitrile to the 20 weight % described in the preparation example 1-3.At this moment, the benzene concentration in the aqueous medium (I) is 1.6ppm.The 1M phosphate aqueous solution of interpolation and its equivalent in reaction solution stops reaction, with the Methacrylamide concentration of HPLC assay determination generation.Then, calculate the formation speed (=speed of response) of the per unit wet thallus and the Methacrylamide in unit reaction times.The results are shown in table 1-3.Speed of response with gained is 100%, compares with embodiment 1-7, comparative example 1-4.
[embodiment 1-7]
Nitrile compound is converted into amide compound (7)
Add benzene in the methacrylonitrile described in the preparation example 1-3, the benzene concentration of modulating in methacrylonitrile is 20ppm.Used methacrylonitrile is replaced with this methacrylonitrile, operate in the same manner with embodiment 1-6.Benzene concentration in aqueous medium this moment (I) is 4.0ppm.The results are shown in table 1-3.
[comparative example 1-4]
Nitrile compound is converted into amide compound (4)
Add benzene in the methacrylonitrile described in the preparation example 1-3, the benzene concentration of modulating in methacrylonitrile is 25ppm.Used methacrylonitrile is replaced with this methacrylonitrile, operate in the same manner with embodiment 1-6.Benzene concentration in aqueous medium this moment (I) is 5.0ppm.The results are shown in table 1-3.
[embodiment 1-8]
Nitrile compound is converted into amide compound (8)
Used wet thallus is replaced with the wet thallus of modulating gained among the routine 1-2, operate in the same manner with embodiment 1-6.The results are shown in table 1-4.Speed of response with gained is 100%, compares with embodiment 1-9, comparative example 1-5.
[embodiment 1-9]
Nitrile compound is converted into amide compound (9)
Used wet thallus is replaced with the wet thallus of modulating gained among the routine 1-2, operate in the same manner with embodiment 1-7.The results are shown in table 1-4.
[comparative example 1-5]
Nitrile compound is converted into amide compound (5)
Used wet thallus is replaced with the wet thallus of modulating gained among the routine 1-2, and 1-4 operates in the same manner with comparative example.The results are shown in table 1-4.
[table 1-1]
Table 1-1
| Benzene concentration (ppm) in the aqueous medium (I) | Relative response speed (%) | |
| Embodiment 1-1 | 0.8 | 100 |
| Embodiment 1-2 | 2.2 | 100 |
| Embodiment 1-3 | 4.0 | 84 |
| Comparative example 1-1 | 5.2 | 69 |
| Comparative example 1-2 | 5.2 | 70 |
Used nitrile compound: vinyl cyanide
Used thalline: contain microbial cells from the nocardial Nitrile hydratase of thermophilic vacation
[table 1-2]
Table 1-2
| Benzene concentration (ppm) in the aqueous medium (I) | Relative response speed (%) | |
| Embodiment 1-4 | 0.8 | 100 |
| Embodiment 1-5 | 4.0 | 85 |
| Comparative example 1-3 | 5.2 | 72 |
Used nitrile compound: vinyl cyanide
Used thalline: contain microbial cells from the Nitrile hydratase of prunosus red coccus
[table 1-3]
Table 1-3
| Benzene concentration (ppm) in the aqueous medium (I) | Relative response speed (%) | |
| Embodiment 1-6 | 1.6 | 100 |
| Embodiment 1-7 | 4.0 | 83 |
| Comparative example 1-4 | 5.0 | 66 |
Used nitrile compound: methacrylonitrile
Used thalline: contain microbial cells from the nocardial Nitrile hydratase of thermophilic vacation
[table 1-4]
Table 1-4
| Benzene concentration (ppm) in the aqueous medium (I) | Relative response speed (%) | |
| Embodiment 1-8 | 1.6 | 100 |
| Embodiment 1-9 | 4.0 | 85 |
| Comparative example 1-5 | 5.0 | 68 |
Used nitrile compound: methacrylonitrile
Used thalline: contain microbial cells from the Nitrile hydratase of prunosus red coccus
[embodiment 1-10]
The preparation of acrylamide
Preparation is equipped with the 1L glass flask of agitator as the 1st reactor, and teflon (registered trademark) tubulation of preparing the 20m internal diameter and be 5mm is as second reactor.Add 400g water in first reactor in advance.
Open the method for 2001-340091 number record according to the spy, cultivate the thalline contain Nitrile hydratase, the wet thallus of gained is suspended in the 0.3mM-NaOH aqueous solution.Speed with 49g/h, 31g/h stirs this suspension liquid and vinyl cyanide b respectively, carries out filler simultaneously continuously in the 1st reactor.Then, from the 1st reactor, take out reaction solution continuously, make the liquid level of the 1st reactor keep certain with the speed of 80g/h.The liquid that takes out is injected the 2nd reactor continuously with the speed of 80g/h, in the 2nd reactor, further react.
It is in 10～20 ℃ the water-bath that the 1st reactor and the 2nd reactor all are immersed in temperature, controlled temperature, and the liquid temperature that makes each inside reactor is 15 ℃.
Regulate the addition of wet thallus, make that the acrylamide transformation efficiency at the 1st reactor outlet is more than 90%, and be (below the 100ppm) below the detectability in the acrylonitrile concentration of second reactor outlet with respect to the 0.3mM-NaOH aqueous solution.Obtain the transformation efficiency that is converted into acrylamide by the analytical results of HPLC.
The result is with respect to the 0.3mM-NaOH aqueous solution, and wet thallus is 2.5 weight %, can reach target conversion.
(comparative example 1-6)
Used vinyl cyanide is replaced with vinyl cyanide a, operate in the same manner with embodiment 1-10.The result is 3.0 weight % for the addition that reaches the required wet thallus of target conversion with respect to the 0.3mM-NaOH aqueous solution.The addition of wet thallus is more than embodiment 1-10, has confirmed the restraining effect of benzene to reaction.
(comparative example 1-7)
Add benzene in vinyl cyanide b, modulate, making the benzene concentration in the vinyl cyanide is 26ppm.Used vinyl cyanide is replaced with this vinyl cyanide, carry out identical operations with embodiment 1-10.The result is 3.0 weight % for the addition that reaches the required wet thallus of target conversion with respect to the 0.3mM-NaOH aqueous solution.The addition of wet thallus is more than embodiment 1-10, has confirmed the restraining effect of benzene to reaction.
(embodiment 1-11)
(PH=5) removes wet thallus with the reaction solution of activated carbon treatment embodiment 1-10 under acidity, further with the 1N-NaOH neutralization, obtains 50 weight % acrylamide solutions.
In the acrylamide solution of gained, add entry, make the acrylamide solution that concentration is 20 weight %.This 20 weight of 500g % acrylamide solution is put into 11 polythene containers, remain on 18 ℃, feeding nitrogen is removed the molten oxygen of depositing in the solution, puts into the insulation block of foamed styrene system immediately.
Then, with 200 * 10
-6Mpm (with respect to the mol ratio of acrylamide) 4,4 '-azo two (4-cyanopentanoic acid sodium), 200 * 10
-6Mpm dimethylaminopropionitrile, and 80 * 10
-6The ammonium persulphate of mpm is dissolved in less water respectively, presses said sequence and injects 1 liter of polythene container rapidly.In mentioned reagent, feed nitrogen in advance, in addition, during injection and before and after injecting, also in above-mentioned polythene container, feed small amount of nitrogen and prevent to sneak into oxygen.
After injecting reagent, the after date of deriving at several minutes has confirmed that the internal temperature of polythene container rises, so stop to supply with nitrogen.Kept polythene container about 100 minutes in insulation block with original state, the internal temperature of polythene container reaches about 70 ℃.Then, polythene container is taken out from insulation block, dipping is 2 hours in 97 ℃ water, and then makes it carry out polyreaction.Then, be immersed in the cold water, cooling stops polyreaction.
From polythene container, take out the aqueous gel of the acrylamide polymer that obtains thus, be divided into fritter, rub with pulverizer.The aqueous gel of the acrylamide polymer after this is rubbed in 100 ℃ hot blast dry 2 hours is further pulverized with high speed rotating cutter pulverizer, obtains dry powdered acrylamide polymer.The dry powdered acrylamide polymer of gained is sieved, separate obtaining 32～42 purpose acrylamide polymers, as the polymer sample that is used for following test.
(comparative example 1-8)
Operate in the same manner with embodiment 1-11, obtain 20 weight % acrylamide solutions by the reaction solution of gained among the comparative example 1-6, further this acrylamide solution of polymerization obtains polymer sample.
(comparative example 1-9)
Operate in the same manner with embodiment 1-11, obtain 20 weight % acrylamide solutions from the reaction solution of comparative example 1-7 gained, further this acrylamide solution of polymerization obtains polymer sample.
The test method of＜acrylamide polymer 〉
Estimate the tone of the polymer sample of gained among the foregoing description 1-11, comparative example 1-8, the comparative example 1-9 according to following method.
Water-soluble: as water-solublely followingly to judge: as in 1 liter of beaker, to add 600ml water, the limit uses the agitating wing of regulation shape to stir down at 25 ℃, 0.66g (pure composition 0.6g) polymer sample is added on the limit, under 400rpm, stirred 2 hours, the solution of gained is with 150 purpose metal mesh filters, water-soluble by what and filterableness judgement of solvent components.That is, consoluet sample is ◎, and approaching consoluet sample is zero, though there is not solvent components, can be △ with the sample of not solvent components elimination, and filtrate is by slowly, the sample that in fact can't filter solvent components not for *.
Tone: the visual inspection polymer powder is estimated the tone of polymkeric substance.
Evaluation result is shown in table 1-5.
[table 1-5]
Table 1-5
| Benzene concentration in the aqueous medium (I) | The solvability of polymkeric substance | The tone of polymkeric substance (visual inspection) | |
| Embodiment 1-11 | 2ppm | ◎ | White |
| Comparative example 1-8 | 10ppm | △ | Faint yellow |
| Comparative example 1-9 | 10ppm | △ | Faint yellow |
2. second inventive embodiment
Below, removing has special qualification, and %, ppm are weight basis.
(embodiment 2-1)
[cultivation contains the thalline of Nitrile hydratase]
Open the method for 2001-340091 number record according to the spy, cultivate the thalline that contains Nitrile hydratase, obtain wet thallus.
[refining vinyl cyanide]
After washing 0.3 liter of resin DIAION WA-20 (trade(brand)name, Mitsubishi change into society's system) with primary amino and/or secondary amino group, it is filled to internal diameter is in 40mm, the long SUS-304 system post for 400mm.Flow with 6 liters/hr feeds the vinyl cyanide that contains the 2ppm propenal in this post.Measure propenal concentration in the refining vinyl cyanide that liquid obtains after by pillar with following high performance liquid chromatography (detect be limited to down 0.1ppm), the result is 0.9ppm.
Analysis condition:
Highly effective liquid phase chromatographic device: LC-6A system (Shimadzu Scisakusho Ltd's system)
(UV detector wavelength is that 210nm, column temperature are 40 ℃)
Separator column: L-Column ODS Type-Waters
((wealth) chemical is checked association's system)
(column dimension: 4.6mm * 250mm)
Elutriant: 20% (volume benchmark)-acetonitrile solution
(being adjusted to pH2.5) with phosphoric acid
[preparation acrylamide]
Preparation is equipped with the 1L glass flask of agitator as the 1st reactor, and Teflon (registered trademark) tubulation of preparing the 20m internal diameter and be 5mm is as second reactor.Add 400g water in first reactor in advance.
To be suspended in according to the wet thallus of above-mentioned cultural method gained in the 0.3mM-NaOH aqueous solution.Speed with 49g/h, 31g/h stirs this suspension liquid and vinyl cyanide respectively, carries out filler simultaneously continuously in the 1st reactor.Speed with 80g/h is taken out reaction solution continuously from the 1st reactor, make the liquid level of the 1st reactor keep certain.Speed with 80g/h is injected the 2nd reactor with the liquid that takes out continuously, and it is further reacted in the 2nd reactor.
It is in 10～20 ℃ the water-bath that the 1st reactor and the 2nd reactor all are immersed in temperature, controlled temperature, and the liquid temperature that makes each inside reactor is 15 ℃.
Regulate the addition of wet thallus with respect to the 0.3mM-NaOH aqueous solution, making the transformation efficiency that is converted into acrylamide at the 1st reactor outlet is more than 90%, and is (below the 100ppm) below the detectability in the acrylonitrile concentration of the 2nd reactor outlet.Obtain the transformation efficiency that is converted into acrylamide by the analytical results of HPLC.
The result is with respect to the 0.3mM-NaOH aqueous solution, and wet thallus is 2.5 weight %, can reach target conversion.
(comparative example 2-1)
Do not carry out the raw material propylene nitrile of ion exchange treatment except that using, carry out identical operations with embodiment 2-1.The result is wet thallus 2.8 weight % for the addition that reaches the required wet thallus of target conversion with respect to the 0.3mM-NaOH aqueous solution.The addition of wet thallus is more than embodiment 2-1, confirms the restraining effect of propenal to reaction.
(comparative example 2-2)
Add propenal in the refining vinyl cyanide of gained in embodiment 2-1, the propenal concentration that transfers in the vinyl cyanide is 2ppm.Use this vinyl cyanide, implement the preparation of acrylamide in the same manner with embodiment 2-1.The result is wet thallus 2.8 weight % for the addition that reaches the required wet thallus of target conversion with respect to the 0.3mM-NaOH aqueous solution.The addition of wet thallus is more than embodiment 2-1, has confirmed the restraining effect of propenal to reaction.
(embodiment 2-2)
(PH=5) removes wet thallus with the reaction solution of activated carbon treatment embodiment 2-1 under acidity, with the 1N-NaOH neutralization, obtains 50 weight % acrylamide solutions again.
In the acrylamide solution of gained, add entry, obtain the acrylamide solution that concentration is 20 weight %.This 20 weight of 500g % acrylamide solution is put into the 1L polythene container, and the limit keeps 18 ℃, and the limit feeds nitrogen, removes the molten oxygen of depositing in the liquid, puts into the insulation block of foamed styrene system then immediately.
Next, respectively with 200 * 10
-64 of mpm (with respect to the mol ratio of acrylamide), 4 '-azo two (4-cyanopentanoic acid sodium), 200 * 10
-6The dimethylaminopropionitrile of mpm, and 80 * 10
-6The ammonium persulphate of mpm is dissolved in less water, presses said sequence and injects 1 liter of polythene container rapidly.In mentioned reagent, feed nitrogen in advance, and before and after injecting and injecting, also in above-mentioned polythene container, inject small amount of nitrogen and prevent to sneak into oxygen.
When injecting reagent, after several minutes inductive phase, rise owing to confirm the polythene container temperature inside, so stop to supply with nitrogen.Kept polythene container about 100 minutes in insulation block with original state, the polythene container temperature inside reaches about 70 ℃.Then, polythene container is taken out from insulation block, dipping is 2 hours in 97 ℃ water, further carries out polyreaction.Next be immersed in the cold water, cooling stops polyreaction.
The aqueous gel of the acrylamide polymer that obtains is thus taken out from polythene container, be divided into fritter, rub with pulverizer.With the aqueous gel of the acrylamide polymer of this rubbing in 100 ℃ hot blast dry 2 hours, further pulverize with high speed rotating cutter pulverizer, obtain dry powdered acrylamide polymer.The dry powdered acrylamide polymer of gained is sieved, separate obtaining 32～42 purpose acrylamide polymers, as the polymer sample that is used for following test.
(embodiment 2-3)
Further to feed the internal diameter that is filled with 0.3 liter of DIAION WA-20 after the washing with the flow of 6 liters/hr be that 40mm, length are that the SUS-304 of 400mm makes in the post for used refining vinyl cyanide in the reaction with embodiment 2-1.Propenal concentration in the refining vinyl cyanide that liquid obtains after by pillar is 0.4ppm.
Use this vinyl cyanide, operate in the same manner with embodiment 2-1 and embodiment 2-2, obtain 20 weight % acrylamide solutions, further this acrylamide solution of polymerization obtains polymer sample.
(comparative example 2-3)
Operate in the same manner with embodiment 2-2, obtain 20 weight % acrylamide solutions by the reaction solution of comparative example 2-1 gained, further this acrylamide solution of polymerization obtains polymer sample.
(comparative example 2-4)
Operate in the same manner with embodiment 2-2, obtain 20 weight % acrylamide solutions by the reaction solution of gained among the comparative example 2-2, further this acrylamide solution of polymerization obtains polymer sample.
The test method(s) of＜acrylamide polymer 〉
Carry out water-soluble evaluation, the normal viscosity of the polymer sample of gained among the foregoing description 2-2, embodiment 2-3, the comparative example 2-2 according to following method and measure, reach the tone evaluation.
Water-soluble: water-soluble as judging: as in the 1L beaker, to put into 600ml water, stir down at 25 ℃ with the agitating wing of regulation shape on the limit, 0.66g (pure composition 0.6g) polymer sample is added on the limit, stirred 2 hours with 400rpm, the solution of gained is with 150 order metal mesh filters, water-soluble by what and filterableness judgement of solvent components.That is, consoluet sample is ◎, and approaching consoluet sample is zero, though have not solvent components, can with this not the sample of solvent components elimination be △, filtrate is by slowly, in fact not solvent components can't filtering sample be *.
Normal viscosity: the filtrate by above-mentioned soluble test gained is that concentration is the aqueous solutions of polymers of 0.1 weight %, add the sodium-chlor that is equivalent to 1M concentration therein, with BL type viscometer, use the BL adapter, under 25 ℃, rotor revolution number is to measure viscosity (normal viscosity) under the condition of 60rpm.The normal viscosity that is obtained by this method is commonly used for the value relevant with molecular weight.
Tone: detect by an unaided eye and estimate the tone that polymer powder is estimated polymkeric substance.
Evaluation result is shown in table 2-1.
[table 2-1]
Table 2-1
| Propenal concentration in the raw material propylene nitrile | The solvability of polymkeric substance | The viscosity of aqueous solutions of polymers (mPas) | The tone of polymkeric substance (visual inspection) | |
| Embodiment 2-2 | 0.9ppm | ○ | 5.8 | White |
| Embodiment 2-3 | 0.4ppm | ◎ | 5.8 | White |
| Comparative example 2-3 | 2ppm | × | Fail to measure * | Faint yellow |
| Comparative example 2-4 | 2ppm | × | Fail to measure * | Faint yellow |
*) filtrate in fact can't be filtered, so fail to measure the viscosity of filtrate by slowly.
Utilizability on the industry
According to the first invention, by utilizing the reaction of nitrile hydratase, can effectively prepare corresponding amide compound by nitrile compound, so be conducive to industrial implementation.
Claims (7)
1, a kind of preparation method of amide compound, described method be have the active catalyzer of Nitrile hydratase in the presence of, in aqueous medium, prepare the method for amide compound by nitrile compound, it is characterized in that the benzene concentration in the aqueous medium is below the 4.0ppm.
2, the preparation method of amide compound as claimed in claim 1, wherein, Nitrile hydratase is the Nitrile hydratase that derives from Pseudonocardia or derive from Rhod.
3, the preparation method of amide compound as claimed in claim 1 or 2, wherein, nitrile compound is vinyl cyanide or methacrylonitrile.
4, a kind of method for preparing acylamide polymer, described method are described amide compound of homopolymerization claim 1 or the described amide compound of copolymerization and can prepare acylamide polymer with at least a unsaturated monomer of amide compound copolymerization.
5, the method for preparing acylamide polymer as claimed in claim 4, wherein, described amide compound is acrylamide or Methacrylamide.
6, a kind of preparation method of acrylamide is characterized in that, it is that the following vinyl cyanide of 1ppm carries out hydration reaction in aqueous medium that described method makes propenal concentration with the thalline of the microorganism that contains Nitrile hydratase or this bacterial disposing thing.
7, a kind of method for preparing acrylamide copolymer, the described acrylamide of described method homopolymerization claim 6, or the described acrylamide of copolymerization and can with at least a unsaturated monomer of acrylamide copolymerization, the preparation acrylamide copolymer.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP295561/2005 | 2005-10-07 | ||
| JP2005295561 | 2005-10-07 | ||
| JP375024/2005 | 2005-12-27 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012103629177A Division CN102911973A (en) | 2005-10-07 | 2006-10-06 | Process for producing amide compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101283102A true CN101283102A (en) | 2008-10-08 |
Family
ID=40014898
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2006800371804A Pending CN101283102A (en) | 2005-10-07 | 2006-10-06 | Process for producing amide compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101283102A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101654414B (en) * | 2009-06-30 | 2012-09-12 | 山东宝莫生物化工股份有限公司 | Process for preparing acrylamide by using spiral-plate reactor |
| CN105008545A (en) * | 2013-02-19 | 2015-10-28 | 三菱丽阳株式会社 | Method for producing amide compound |
| CN112342252A (en) * | 2020-11-09 | 2021-02-09 | 唐山晋广化工有限公司 | Preparation method of 2-amino-2, 3-dimethylbutyramide |
-
2006
- 2006-10-06 CN CNA2006800371804A patent/CN101283102A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101654414B (en) * | 2009-06-30 | 2012-09-12 | 山东宝莫生物化工股份有限公司 | Process for preparing acrylamide by using spiral-plate reactor |
| CN105008545A (en) * | 2013-02-19 | 2015-10-28 | 三菱丽阳株式会社 | Method for producing amide compound |
| CN112342252A (en) * | 2020-11-09 | 2021-02-09 | 唐山晋广化工有限公司 | Preparation method of 2-amino-2, 3-dimethylbutyramide |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102911973A (en) | Process for producing amide compound | |
| KR101289148B1 (en) | Acrylamide methacrylamide production method | |
| JPH11123098A (en) | Production of amide compound | |
| WO2001073101A1 (en) | Process for producing amide compounds | |
| CN101283102A (en) | Process for producing amide compound | |
| CN102844295B (en) | Stable aqueous acrylamide solution | |
| KR101878012B1 (en) | Method for producing aqueous acrylamide solution | |
| CN101370942B (en) | Process for producing (meth)acrylamide | |
| CN101410527B (en) | Method of producing acrylamide | |
| WO2011148867A1 (en) | Method for manufacturing an amide compound | |
| CN101415832A (en) | Process for production of acrylamide | |
| JP2008247979A (en) | Method for producing high-quality (meth)acrylamide polymer | |
| JP2008138089A (en) | Manufacturing method of (meth)acrylamide polymer of high quality | |
| KR101894617B1 (en) | Method for producing acrylamide aqueous solution | |
| AU2011239258B2 (en) | Method for producing amide compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20081008 |