Classifications

• • 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
  • C12P7/00—Preparation of oxygen-containing organic compounds
  • C12P7/62—Carboxylic acid esters

Definitions

• the present invention relates to a method for producing a glycerin carbonate acrylate compound by reacting glycerin carbonate with a vinyl acrylate compound.
• the glycerin carbonate acrylate compound is a compound useful as a raw material for, for example, paints, coating materials, photo-curing resins, and other resins, and more specifically, disclosed for application to electrolytic solutions and photosensitive resins. (For example, refer nonpatent literature 1).
• a method for producing a glycerol carbonate acrylate compound from glycerol carbonate for example, a method of reacting glycerol carbonate and methyl acrylate in the presence of a base catalyst such as sodium methoxide (for example, see Patent Document 1), or zirconium
• a base catalyst such as sodium methoxide (for example, see Patent Document 1), or zirconium
• a metal catalyst such as a complex
• the by-produced alcohol may decompose glycerin carbonate under basic conditions (or even under acidic conditions) (see Patent Document 3).
• popcorn polymerization is a phenomenon in which polymerization occurs explosively with high-temperature polymerization heat starting from the formation of a core polymer in the gas phase, and is a porous and bulky polymerization. Produce things. If popcorn polymerization occurs during production on a large scale, there is a risk of equipment breakage and explosion due to equipment blockage, so a low temperature production method that does not increase the concentration of vinyl compounds in the gas phase has been sought. .
• lipase which is a hydrolase, recognizes the three-dimensional structure of the substrate itself, so in the reaction using a stereoisomer mixture, one of the isomers. Since only the reaction occurs, even if the selectivity for the target product is close to 100%, the yield is at most 50% (for example, see Non-Patent Document 3).
• the present invention 1 is a compound of formula (I) in the presence of lipase.
• R 2 is a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms
• R 3 is a hydrogen atom or a linear or branched chain having 1 to 10 carbon atoms.
• It is a chain or cyclic alkyl group
• the present invention 2 provides that the lipase originates from Burkholderia cepacia, lipase from Candida antarctica, Thermomyces lanuginosus and Thermomyces lamus It is related with the manufacturing method of the glycerol carbonate acrylate compound of this invention 1 which is 1 or more types selected from the group which consists of a lipase.
• the present invention 3 relates to a process for producing the glycerin carbonate acrylate compound of the present invention 1 or 2, wherein the reaction is carried out at 0 to 100 ° C.
• the present invention 4 relates to a process for producing a glycerin carbonate acrylate compound according to any one of the present invention 1 to 3, wherein the reaction is carried out in an organic solvent.
• the present invention 5 relates to the method for producing a glycerin carbonate acrylate compound of the present invention 4, wherein the organic solvent is one or more selected from the group consisting of tert-butyl alcohol and 2-methyl 2-butanol.
• the present invention 6 relates to the method for producing a glycerol carbonate acrylate compound according to any one of the present inventions 1 to 5, wherein the amount of lipase used is 0.1 to 10,000 mg with respect to 1.0 g of glycerol carbonate.
• the present invention 7 relates to the method for producing a glycerin carbonate acrylate compound according to any one of the present inventions 1 to 6, wherein the vinyl acrylate compound is used in an amount of 1.0 to 60 mol per 1 mol of glycerin carbonate.
• the present invention 8 relates to the method for producing a glycerol carbonate acrylate compound according to any one of the present inventions 1 to 8, wherein the lipase is a lipase originating from Burkholderia cepacia.
• the present invention 9 relates to the process for producing a glycerin carbonate acrylate compound according to any one of the present inventions 1 to 8, wherein the lipase is a lipase originating from Candida antarctica.
• the present invention 10 relates to a method for producing a glycerin carbonate acrylate compound according to any one of items 1 to 8, wherein the lipase is a lipase originating from Thermomyces
• a glycerol carbonate acrylate compound can be produced from glycerol carbonate and a vinyl acrylate compound in the presence of lipase without using a basic catalyst or a metal component.
• the method of the present invention can be suitably applied to reactions using glycerin carbonate (isomer mixture) having asymmetric carbon as a raw material. According to the method of the present invention, it is also possible to obtain the glycerin carbonate acrylate compound which is the target product with a high yield exceeding 50%.
• the reaction of the present invention is to produce a glycerol carbonate acrylate compound by reacting glycerol carbonate with a vinyl acrylate compound in the presence of lipase (see the following formula).
• the glycerin carbonate of the formula (I) may be produced by any method.
• the glycerin carbonate may be a pure optical isomer or a mixture of isomers, and a racemic mixture can also be used.
• the vinyl acrylate compound used in the present invention is represented by the following formula (II).
• R 2 is a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms
• R 3 is a hydrogen atom or a linear or branched alkyl group having 1 to 10 carbon atoms. Or a cyclic alkyl group.
• R 2 is a linear or branched alkyl group having 1 to 4 carbon atoms, examples thereof include a methyl group, an ethyl group, a propyl group, an isopropyl group, an n-butyl group, an isobutyl group, and a sec-butyl group. Can be mentioned.
• R 2 is preferably a hydrogen atom or a methyl group.
• R 3 is a linear, branched or cyclic alkyl group having 1 to 10 carbon atoms, for example, methyl group, ethyl group, propyl group, butyl group, pentyl group, hexyl group, octyl group, decyl group, A cyclopentyl group and a cyclohexyl group are mentioned.
• R 3 is preferably a hydrogen atom, a methyl group, or an ethyl group.
• Examples of the vinyl acrylate compound of the formula (II) include acrylate alkenyl esters such as vinyl acrylate and isopropenyl acrylate, methacrylic acid alkenyl esters such as vinyl methacrylate and isopropenyl methacrylate, and the like.
• the vinyl acrylate compound of the formula (II) may be used alone or in combination of two or more.
• the amount of the vinyl acrylate compound used can be 1.0 to 60 mol, preferably 1.0 to 5.0 mol, per 1 mol of glycerin carbonate.
• the lipase used in the present invention is not particularly limited as long as it is a lipase capable of obtaining a glycerol carbonate acrylate compound in high yield from glycerol carbonate and a vinyl acrylate compound.
• lipases originating from cepacia eg Amano PS (manufactured by Amano Enzyme)
• lipases originating from Candida antarctica eg Novozym 435 (manufactured by Novozyme)
• Thermomyces lanuginosus Lipase TL originating from Thermomyces lanuginosus, particularly preferably a lipase originating from Burkholderia cepacia (eg Amano PS (manufactured by Amano Enzyme)), Candida antarctica Lipase originating from (Candida antarctica)
• a Novozym 435 Novozymes Co., Ltd.
• lipases were obtained from recombinant cultures obtained by introducing a lipase-encoding gene obtained from a microorganism as described above into an appropriate host such as yeast or filamentous fungus. Also good.
• the amino acid sequence of the lipase is not limited to those described above.
• a protein having a lipase activity consisting of an amino acid sequence in which one or several amino acids are deleted, substituted or added in these sequences is provided in the present invention. Can be suitably used.
• a protein consisting of an amino acid sequence having a sequence identity of, for example, 90% or more, preferably 95%, more preferably 97% or more with these sequences, and having lipase activity can also be suitably used in the present invention. it can.
• lipase forms are not particularly limited, and may be natural or immobilized enzyme forms.
• Immobilized enzyme refers to an immobilized carrier carrying lipase by adsorption or the like.
• immobilization carriers include celite, diatomaceous earth, kaolinite, silica gel, molecular sieves, porous glass, activated carbon, calcium carbonate, ceramics and other inorganic carriers, polyvinyl alcohol, polypropylene, chitosan, ion exchange resins, hydrophobic adsorption resins, chelates.
• organic polymers such as resins and synthetic adsorbents. Synthetic adsorbents are particularly preferable from the viewpoint of high adsorbability of enzymes.
• porous materials are preferable because they have a large surface area and can increase the amount of adsorbed enzyme.
• Lipase may be used alone or in combination of two or more.
• the amount of lipase used is preferably 0.1 to 10,000 mg, more preferably 1 to 500 mg, particularly preferably 1.0 to 500 mg, based on 1.0 g of glycerol carbonate of the formula (I), from the viewpoint of realizing an efficient reaction rate. 10 to 200 mg is preferable.
• the reaction system is not particularly limited, and any system including a batch system or a continuous flow system in which a lipase-immobilized column is passed can be used.
• the reaction of the present invention can be carried out using an organic solvent.
• the organic solvent is not particularly limited as long as it is a solvent that can uniformly dissolve the glycerin carbonate and the vinyl acrylate compound as substrates and does not deactivate the lipase.
• the organic solvent examples include alcohols such as tert-butyl alcohol and 2-methyl-2-butanol, particularly preferably tert-butyl alcohol.
• the reaction of the present invention is a transesterification reaction, glycerin carbonate and vinyl acrylate can be used without causing the alcohol to participate in the reaction even if these alcohols are used as the organic solvent by performing in the presence of lipase. It was found that the reaction with the compound proceeds.
• These organic solvents may be used alone or in combination of two or more.
• the amount of the organic solvent used is preferably 0.1 to 100 mL, more preferably 0.2 to 50 mL, and particularly preferably 0.5 to 5 mL with respect to 1 g of glycerol carbonate of the formula (I).
• the reaction of the present invention is preferably carried out in the presence of a polymerization inhibitor in order to prevent polymerization of the acrylate moiety.
• the polymerization inhibitor is not particularly limited as long as it is normally used. For example, phenol, cresol, hydroquinone, t-butylhydroquinone, p-methoxyphenol (methoquinone), 2,6-di-t-butyl-4 -Methylphenol, phenothiazine, etc. can be used.
• the amount of the polymerization inhibitor used is preferably 0.000001 to 0.05 mol, more preferably 0.000002 to 0.03 mol, per 1 mol of glycerin carbonate.
• reaction temperature can be 0 to 100 ° C., preferably 10 to 90 ° C., more preferably 30 to 70 ° C.
• reaction pressure is not particularly limited, and the reaction can be performed under normal pressure or reduced pressure.
• the method of the present invention can perform the reaction at a lower temperature than the case of performing the transesterification reaction at normal pressure while refluxing the acrylate ester, and is excellent in efficiency and safety.
• the reaction of the present invention can be carried out in a continuous flow manner.
• the concentration of the glycerin carbonate compound in the reaction solution is preferably 5 to 50% by mass with respect to the total mass of the reaction system, and the concentration of the vinyl acrylate compound is The content is preferably 5 to 30% by mass with respect to the total weight.
• the flow rate of the reaction liquid is preferably 0.5 to 400 mm / min, more preferably 1 to 200 mm / min.
• the liquid flow rate (mm / min) is the cross-sectional area of the packed bed (mm 2 ) by the amount of liquid fed per minute (mm 3 / min) (or also called the liquid feed rate (10 ⁇ 3 mL / min)). The value expressed by the quotient divided by.
• the liquid passage speed is 400 mm / min or less. Further, from the viewpoint of productivity, it is preferable that the liquid flow rate is 1 mm / min or more. Since the expression activity of the immobilized enzyme varies depending on the flow rate, the reaction can be performed according to the desired production capacity and manufacturing cost by selecting the optimal flow rate and determining the reaction conditions. it can.
• the flow time of the reaction solution in the reaction vessel can be in the range of 30 seconds to 6 hours.
• a glycerin carbonate acrylate compound having a purity of 80% or more can be obtained by distilling off low-boiling components such as a solvent and a vinyl acrylate compound under reduced pressure after the reaction.
• the purity of the glycerin carbonate acrylate compound can be calculated from the area percentage by gas chromatography analysis.
• the raw material glycerol carbonate remains, it can be removed by an extraction operation.
• the glycerin carbonate acrylate compound obtained by the production method of the present invention can be further purified by general methods such as distillation, liquid separation, extraction, crystallization, recrystallization and column chromatography.
• the glycerin carbonate acrylate compound obtained by the production method of the present invention is produced using lipase. For this reason, the possibility of contamination by impurities such as metal salts or halides that can occur in the conventional method for producing glycerin carbonate acrylate compounds is extremely low, and a chemically safer product can be obtained.
• the glycerin carbonate acrylate compound obtained by the production method of the present invention can be, for example, emulsion-polymerized with a (meth) acrylic monomer to form an acrylic emulsion.
• This acrylic emulsion can be used in a coating composition, but is suitable for a coating material for an electronic substrate and the like because there is no mixing of a metal salt or the like into glycerin carbonate acrylate.
• the method for producing the acrylic emulsion is not particularly limited, and a reactive emulsifier is added to the glycerin carbonate acrylate compound, the (meth) acrylic monomer, and optionally other unsaturated monomers, and the mixture is stirred. After making into an emulsion, it can manufacture by adding a polymerization initiator and carrying out emulsion polymerization.
• Examples of the (meth) acrylic monomer include linear or branched alkyl esters of 1 to 6 carbon atoms of (meth) acrylic acid, specifically, methyl (meth) acrylate, (meth ) Ethyl acrylate, propyl (meth) acrylate, butyl (meth) acrylate, (meth) acrylamide and the like.
• Examples of other unsaturated monomers include styrene and ⁇ -methylstyrene.
• Examples of the reactive emulsifier include polyoxyalkylene alkyl ether sulfate sodium salt, polyoxyalkylene oleyl ether sulfate sodium salt, and polyoxyalkylene alkylphenyl ether sulfate ester salt.
• Examples of the polymerization initiator include peroxides such as benzoyl peroxide, t-butyl hydroperoxide, cumene hydroperoxide, and azobis compounds such as 2,2-azobisisobutyronitrile.
• the lipase used in the reaction of the present invention is as follows.
• Novozyme 435 a product obtained by immobilizing Candida antarctica lipid B from Novozyme on a porous resin carrier.
• AmanoPS-C A lipase derived from Burkholderia cepacia manufactured by Amano Enzyme Co., Ltd. adsorbed and immobilized on a porous ceramic carrier.
• AmanoPS-IM A lipase derived from Burkholderia cepacia manufactured by Amano Enzyme and adsorbed and immobilized on a celite carrier.
• Immobilized lipase Pseudomonas sp lipase manufactured by Wako Pure Chemical Industries, immobilized on an inorganic carrier.
• Lipase OF A lipase derived from Candida cylindracea manufactured by Meito Sangyo.
• Lipozyme RM IM A lipase derived from Rhizomucor miehei immobilized on an ion exchange resin.
• PFL Sol-Gel
• CalA Candida antarctica lipase A lipase produced by Sigma, immobilized by CLEA method (Cross-Linked-Enzyme-Aggregates).
• Lipase TL (CLEA): A lipase derived from Thermomyces langinosus manufactured by Sigma, immobilized by CLEA method (Cross-Linked-Enzyme-Aggregates).
• the immobilized enzyme was removed by filtration, and then the filtrate was concentrated under reduced pressure to obtain 15.9 g of a pale yellow liquid.
• the fraction containing the target product was concentrated to obtain 10.2 g of a colorless transparent liquid. From 1 H-NMR, the powder was identified as glycerin carbonate methacrylate.
• Example 2 Synthesis of glycerol carbonate methacrylate with various lipases
• glycerin carbonate Glycerol 1,2-Carbonate: manufactured by Tokyo Chemical Industry, racemic mixture
• vinyl methacrylate 576 mg
• triglyme as an internal standard substance
• 40.0 mg of various lipases were mixed with the reaction solution, which was adjusted to 2.0 ml by adding tert-butyl alcohol and stirred. The reaction was allowed to proceed for 24 hours at ° C.
• reaction yield was calculated by quantifying the product amount from a standard product and a calibration curve of the internal standard ratio. The results are shown in Table 1.
• lipases originating from Burkholderia cepacia for example, AmanoPS (manufactured by Amano Enzyme)
• Candida antarctica Lipase B Only a lipase originating from C. (for example Novozyme 435 (manufactured by Novozyme)) and a lipase originating from Thermomyces lanuginosus (LipaseTL) showed high yields exceeding 50%. It can be seen that when these lipases are used, the reaction proceeds regardless of the three-dimensional structure of the substrate.
• Example 3 Synthesis of glycerol carbonate methacrylate with various reaction solvents
• glycerin carbonate Glycerol 1,2-Carbonate: manufactured by Tokyo Chemical Industry, racemic mixture
• vinyl methacrylate 576 mg
• triglyme as an internal standard substance
• lipase AmanoPS-IM
• reaction yield was calculated by quantifying the product amount from a standard product and a calibration curve of the internal standard ratio. The results are shown in Table 2.
• Example 4 Synthesis of glycerol carbonate methacrylate with various reaction temperatures and vinyl methacrylate addition amount
• a glass container having an internal volume of about 19 ml equipped with a stirrer, temperature control and upper cooling device, 400 mg (3.39 mmol) of glycerin carbonate (Glycerol 1,2-Carbonate: manufactured by Tokyo Chemical Industry, racemic mixture), 576 mg of vinyl methacrylate. (5.14 mmol) or 762 mg (6.80 mmol), 40.0 mg of triglyme as an internal standard substance, tert-butyl alcohol was added, and lipase was mixed with the reaction solution to a constant volume of 2.0 ml.
• glycerin carbonate Glycerol 1,2-Carbonate: manufactured by Tokyo Chemical Industry, racemic mixture
• triglyme as an internal standard substance
• tert-butyl alcohol was added, and lipase was mixed with the reaction solution to a constant volume of 2.0 ml.
• the reaction was carried out at the predetermined reaction temperature for 24 hours with stirring. During the reaction, 50 ⁇ l of the reaction solution was sampled over time, 950 ⁇ l acetone added was filtered, and 1.0 ⁇ l was subjected to gas chromatographic analysis. The reaction yield was calculated by quantifying the product amount from a standard product and a calibration curve of the internal standard ratio. The results are shown in Table 3.
• Example 5 Isolation yield and purity of glycerol carbonate methacrylate
• a glass three-necked flask with an internal volume of 1 L equipped with a stirrer, temperature control and upper cooling device was charged with 100 g (0.85 mol) of glycerin carbonate (Glycerol 1,2-Carbonate: Tokyo Kasei purity 90.1%, racemic mixture).
• 191 g of vinyl methacrylate (1.7 mol: purity 99.9%, manufactured by Tokyo Chemical Industry) and 20.0 mg of p-methoxyphenol as a polymerization inhibitor were added, and then 200 g of tert-butyl alcohol was added to make uniform.
• the non-volatile component of the emulsion was 42.0 mass%, and the viscosity was 20 mPa * S.
• the viscosity is a value measured at 23 ° C. with a BM viscometer at a rotation speed of 60 rpm.
• a glycerol carbonate acrylate compound can be produced from glycerol carbonate and a vinyl acrylate compound using a certain kind of lipase without using a protonic acid or a metal component.
• the method of the present invention can be suitably applied to a reaction in which glycerin carbonate (racemic mixture) having asymmetric carbon is used as a raw material, and is convenient.
• glycerin carbonate racemic mixture
• the method of the present invention can perform the reaction at a relatively low temperature, and is excellent in terms of efficiency and safety.
• a highly purified glycerol carbonate acrylate compound can be obtained by the method of the present invention. That is, according to the present invention, a high-quality glycerin carbonate acrylate compound can be easily produced by using an easily available raw material.

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• 2013
  • 2013-02-27 WO PCT/JP2013/055171 patent/WO2013129486A1/fr not_active Ceased
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