JP5949563B2 - Method for producing isocyanate compound - Google Patents

Description

  The present invention relates to a method for producing an isocyanate compound. More specifically, the present invention relates to a method for producing an isocyanate compound by thermally decomposing a carbamate compound (carbamic acid ester compound). More specifically, the present invention relates to a method capable of producing an isocyanate compound with high selectivity by rapidly raising a carbamate compound to a thermal decomposition temperature and then rapidly cooling the carbamate compound.

  Conventionally, an isocyanate compound is industrially produced from a reaction between an amine and phosgene. However, this method has problems such as (1) phosgene is extremely toxic and needs to be handled with care, and (2) by-produces a large amount of hydrogen chloride that corrodes the apparatus. For this reason, the industrial manufacturing method of isocyanates replaced with this method is strongly desired.

  Recently, methods for producing isocyanate compounds that do not use phosgene have been studied. For example, a method in which a solid catalyst such as silicate and an organic tin compound are used in a high boiling point solvent under reduced pressure (see, for example, Patent Document 1), in a high boiling point solvent, zinc, aluminum, titanium, iron, chromium, cobalt, or A method using nickel as a catalyst (for example, see Patent Document 2), a method for performing in a gas phase under reduced pressure in a reaction tube filled with stainless steel, copper wire, and quartz at 350 to 550 ° C. (for example, see Patent Document 3) There is known a method of performing a gas phase using an oxide sintered body of at least one element selected from the group consisting of Group IIIa elements, Group IVa elements and Group Va elements as a catalyst (for example, see Patent Document 4). Yes.

  Further, a method of synthesizing a carbamate compound from an amine compound and an alkylaryl carbonate, recovering a low boiling point component from the reaction solution as a gas phase component, and then thermally decomposing using a tin catalyst to obtain an isocyanate compound (for example, patents) Reference 5), a method of synthesizing a carbamate compound from an amine compound and dialkyl carbonate using sodium methoxide, distilling off low boiling components from the reaction solution, and then obtaining an isocyanate compound by thermal decomposition with a tin catalyst (for example, Patent Document 6), a method of synthesizing a carbamate compound from an amine compound and dialkyl carbonate using sodium methoxide, distilling off low-boiling components from the reaction solution, and then obtaining an isocyanate compound by thermal decomposition with a tin catalyst ( For example, see Patent Document 7), an amine compound and diphenyl carbonate, Was synthesized Min acid phenyl ester, a method of obtaining an isocyanate compound by thermal decomposition (e.g., see Patent Document 8), it is known.

JP 2004-262892 A JP-A-56-65857 JP 50-117745 A JP-A-5-186415 Japanese Patent No. 4298995 International Publication No. 2008/084824 International Publication No. 2009/139062 International Publication No. 2009/139061

  However, the methods described in Patent Documents 1 to 4 have problems that the activity of the catalyst is not sufficient, or that it is difficult to recover and reuse the catalyst. Further, since the inside of the reaction tube is filled with a solid catalyst or a packing, there is a problem that the reaction tube is blocked. Therefore, a method for producing an isocyanate compound capable of preventing the reaction tube from being blocked has been desired. In addition, a method capable of producing an isocyanate compound from a carbamate compound at a high reaction rate and in a high yield has been desired.

  The methods described in Patent Documents 5 to 7 have a problem that it is necessary to recover a low boiling point component from a reaction solution containing a carbamate compound before thermal decomposition.

  Since the method of Patent Document 8 uses highly reactive diphenyl carbonate, a very large number of urea compounds which are undesirable in carbamate formation are by-produced, and the apparatus must be periodically cleaned during thermal decomposition. was there. Further, since phenol having a high melting point is used, there is a problem that it is difficult to recover and reuse the raw material.

  An object of the present invention is to prevent clogging of a reaction tube when an isocyanate compound is produced. Moreover, it aims at manufacturing an isocyanate compound with a high reaction rate and a high yield only by thermal decomposition.

The method of the present invention is as follows.
A method for producing an isocyanate compound, comprising:
Supplying a carbamate compound together with a carrier gas into a hollow space not containing a solid catalyst and / or packing;
Thermally decomposing the carbamate compound in the hollow space,
A value (N) obtained by dividing the volume of the hollow space by the total supply amount per unit time of the carbamate compound and the carrier gas is 0.001 or more and 2 or less.
A method for producing an isocyanate compound.

  In the method of the present invention, the carbamate compound is preferably thermally decomposed at a temperature of 450 ° C. or higher and 600 ° C. or lower.

  In the method of the present invention, the carbamate compound is preferably a compound represented by the following general formula (1).

(In the formula, R ¹ and R ² represent a hydrocarbon group. R ¹ and R ² may be the same as or different from each other. R ¹ and R ² may have a substituent. N is an integer of 1 or more and 4 or less.

In the method of the present invention, in the presence of an enzyme, an amine compound represented by the following general formula (2) and a carbonate compound represented by the following general formula (3) are placed in the reaction vessel in the presence or absence of a solvent. And the step of supplying the resulting reaction liquid to the hollow space after the reaction under
The solvent is preferably at least one selected from the group consisting of aliphatic hydrocarbons, aromatic hydrocarbons, and acyclic ethers.

(In the formula, R ¹ represents a hydrocarbon group which may have a substituent. N represents an integer of 1 or more and 4 or less.)

(In the formula, R ² represents a hydrocarbon group which may have a substituent.)

  In the method of the present invention, the isocyanate compound is preferably a compound represented by the following general formula (4).

(In the formula, R ¹ represents a hydrocarbon group which may have a substituent. N represents an integer of 1 or more and 4 or less.)

  In the method of the present invention, the aromatic compound is preferably toluene or xylene.

  In the method of the present invention, it is preferable that a fixed bed on which the enzyme is fixed is installed inside the reaction vessel.

  In the method of the present invention, the reaction solution is preferably supplied to the hollow space after passing through a filter.

  According to the present invention, when an isocyanate compound is produced, the reaction tube can be prevented from being blocked. Moreover, an isocyanate compound can be produced at a high reaction rate and in a high yield only by thermal decomposition.

The manufacturing apparatus of the isocyanate compound provided with the hollow space is shown. The manufacturing apparatus of the isocyanate compound provided with the hollow space is shown. A rod-shaped stainless steel wire is arranged inside the hollow space.

Hereinafter, embodiments of the present invention will be described.
In the method of the present invention, a hollow reaction tube is used in which the cross-sectional shape of an arbitrary part from the inlet to the outlet is substantially equal. A hollow space is formed inside the hollow reaction tube. By heating the hollow reaction tube, a thermal decomposition reaction of the carbamate compound can proceed inside the hollow reaction tube.

  As the hollow reaction tube, it is preferable to use a metal circular tube of any length having a circular cross-sectional shape. As the hollow reaction tube, a metal member having a cross-sectional shape such as a rectangle or a polygon can be used in addition to a circle.

A hollow space is formed inside the hollow reaction tube.
The hollow reaction tube does not contain a solid catalyst and / or packing (for example, particulate stainless steel, copper wire, quartz, etc.).

It is preferable to arrange a partition member inside the hollow reaction tube. By arranging the partition member, the inside of the hollow reaction tube can be partitioned into a plurality of spaces. Moreover, the temperature inside the hollow reaction tube can be easily controlled by arranging the partition member.
As the partition member, it is preferable to use a member that does not easily block the reaction tube. For example, as a partition member, it is preferable to use the rod-shaped member extended along the longitudinal direction of a reaction tube.

The carbamate compound used in the method of the present invention is represented by the following general formula (1). The carbamate compound is a substance having at least one urethane bond (—NHCO ₂ —) in the molecule.

(In the formula, R ¹ and R ² represent a hydrocarbon group. R ¹ and R ² may be the same as or different from each other. R ¹ and R ² may have a substituent. N is an integer of 1 or more and 4 or less.

In the above formula (1), examples of the hydrocarbon group represented by R ¹ and R ² include, for example, methyl group, ethyl group, propyl group, butyl group, pentyl group, hexyl group, octyl group, 2-ethylhexyl. An alkyl group having 1 to 18 carbon atoms such as a group, nonyl group, decyl group, dodecyl group and octadecyl group; an alkenyl group having 2 to 6 carbon atoms such as a propenyl group, a butenyl group, a pentenyl group and a hexenyl group; an ethylidene group Alkylidene groups having 2 to 6 carbon atoms such as propylidene group, butylidene group, pentylidene group, hexylidene group; cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, methylcyclohexyl group, cyclooctyl group, dimethylcyclohexyl group, isophorone Group, norbornylene group, decalin group, adamantyl group, etc. A cycloalkyl group having a number of 3 to 10; an aryl group having 6 to 14 carbon atoms such as a phenyl group, a tolyl group, a xylyl group, a naphthyl group, a biphenyl-4-yl group, an anthryl group and a trimethylphenyl group; a methylene group and an ethylene group Group, propylene group, butylene group, pentylene group, hexylene group, heptylene group, octylene group, nonylene group, decylene group, dodecylene group, 2-methylpropylene group, 2-methylhexylene group, tetramethylethylene group, etc. A linear or branched alkylene group having 1 to 20 atoms; cyclopropylene group, cyclobutylene group, cyclopentylene group, cyclohexylene group, methylene-cyclopentylene-methylene group, ethylene-cyclopentylene- Ethylene group, methylene-cyclohexylene-methylene group, methylene-trimethylcyclo Monocyclic or polycyclic having 3 to 20 carbon atoms such as hexyl group, bicyclohexylene group, methylenebiscyclohexylene group, bicyclo [2.2.1] heptane-2,6-diyl group, adamantylene group, etc. A cycloalkylene group; an arylene group having 6 to 20 carbon atoms such as a phenylene group, a tolylene group, a xylylene group, a naphthylene group, a biphenylene group, an anthrylene group, and a trimethylphenylene group; Examples thereof include an alkylarylene group containing a monocyclic or polycyclic aromatic ring. These groups include various isomers.

In the above formula (1), the hydrocarbon group represented by R ¹ and R ² may have a substituent. Examples of the substituent include a hydroxyl group, a halogen atom, a cyano group, an amino group, an alkylamino group, a carboxyl group, an alkoxy group, an aryloxy group, an alkylthio group, an arylthio group, and a (meth) acryloyloxy group. It is done.

In the above formula (1), n is an integer of 1 or more and 4 or less. Note that n is determined by the valence of R ¹ . When R ¹ is a monovalent group (for example, a cyclohexyl group), n is 1. When R ¹ is a divalent group (for example, cyclohexylene group), n is 2.

  Examples of carbamate compounds used in the method of the present invention include methyl (N-hexyl) carbamate, methyl (N-octyl) carbamate, methyl (N-dodecyl) carbamate, methyl (N-octadecyl) carbamate, 1,4- Bis (methoxycarbonylamino) butane, 1,4-bis (ethoxycarbonylamino) butane, 1,4-bis (butoxycarbonylamino) butane, 1,5-bis (methoxycarbonylamino) pentane, 1,6-bis ( Methoxycarbonylamino) hexane, 1,6-bis (ethoxycarbonylamino) hexane, 1,6-bis (butoxycarbonylamino) hexane, 1,8-bis (methoxycarbonylamino) octane, 1,8-bis (butoxycarbonyl) Amino) octane, 1,8-bis ( Phenoxycarbonylamino) -4- (phenoxycarbonylaminomethyl) octane, 1,9-bis (methoxycarbonylamino) nonane, 1,9-bis (butoxycarbonylamino) nonane, 1,10-bis (methoxycarbonylamino) ) -Decane, 1,12-bis (butoxycarbonylamino) -dodecane, 1,12-bis (methoxycarbonylamino) -dodecane, 1,12-bis (phenoxycarbonylamino) -dodecane, 1,3,6-tris Aliphatic carbamate compounds such as (methoxycarbonylamino) hexane and 1,3,6-tris (phenoxycarbonylamino) hexane; 1,3- or 1,4-bis (methoxycarbonylamino) cyclohexane, 1,3- or 1,4-bis (ethoxycarbonylamino) cyclohex 1,3- or 1,4-bis (butoxycarbonylamino) cyclohexane, 1,3- or 1,4-bis (methoxycarbonylaminomethyl) cyclohexane, 1,3- or 1,4-bis (ethoxycarbonyl) Aminomethyl) cyclohexane, 1,3- or 1,4-bis (butoxycarbonylaminomethyl) cyclohexane, 2,4′- or 4,4′-bis (ethoxycarbonylamino) dicyclohexanemethane, 2,4′- or 4,4′-bis (methoxycarbonylamino) dicyclohexylmethane, 2,4′- or 4,4′-bis (butoxycarbonylamino) dicyclohexylmethane, 2,5-bis (methoxycarbonylaminomethyl) bicyclo [2,2 , 1] heptane, 2,5-bis (butoxycarbonylaminomethyl) bicyclo [2,2,1] heptane, 2,6-bis (methoxycarbonylaminomethyl) bicyclo [2,2,1] heptane, 2,6-bis (butoxycarbonylaminomethyl) bicyclo [2,2,1] heptane 1- (methoxycarbonylamino) -3,3,5-trimethyl-5- (methoxycarbonylaminomethyl) -cyclohexane, 1- (butoxycarbonylamino) -3,3,5-trimethyl-5- (butoxycarbonylamino) Methyl) -cyclohexane, 3-methoxycarbonylaminomethyl-3,5,5-trimethyl-1-methoxycarbonylaminocyclohexane, 4,4′-bis (methoxycarbonylamino) -2,2′-dicyclohexylpropane, 4,4 '-Bis (butoxycarbonylamino) -2,2'-dicyclohexylpro Alicyclic carbamate compounds such as 1,3- or 1,4-bis (methoxycarbonylaminomethyl) benzene, 1,3- or 1,4-bis (ethoxycarbonylaminomethyl) benzene, 1,3- Or 1,4-bis (butoxycarbonylaminomethyl) benzene, 1,3- or 1,4-bis (methoxycarbonylamino) benzene, 1,3- or 1,4-bis (butoxycarbonylamino) benzene, 2, 4′- or 4,4′-bis (methoxycarbonylamino) diphenylmethane, 2,4′-bis (ethoxycarbonylamino) diphenylmethane, 2,4′-bis (butoxycarbonylamino) diphenylmethane, 4,4′-bis ( Phenoxycarbonylamino) diphenylmethane, 1,5- or 2,6-bis (methoxycarbonyla) C) naphthalene, 1,5- or 2,6-bis (butoxycarbonylamino) naphthalene, 4,4′-bis (methoxycarbonylamino) biphenyl, 4,4′-bis (butoxycarbonylamino) biphenyl, 2,4 -Or 2,6-bis (methoxycarbonylamino) toluene, 2,4- or 2,6-bis (ethoxycarbonylamino) toluene, 2,4- or 2,6-bis (butoxycarbonylamino) toluene, 2, And aromatic carbamate compounds such as 2-bis (4-propoxycarbonylaminophenyl) propane. In addition, the substituent on N or O of these compounds includes various isomers. These carbamate compounds may be used alone or in combination of two or more.

  The amine compound used in the method of the present invention is represented by the following general formula (2).

(In the formula, R ¹ represents a hydrocarbon group which may have a substituent. N represents an integer of 1 or more and 4 or less.)

In the above formula (2), examples of the hydrocarbon group represented by R ¹ include methyl group, ethyl group, propyl group, butyl group, pentyl group, hexyl group, octyl group, 2-ethylhexyl group, nonyl group, Alkyl groups having 1 to 18 carbon atoms such as decyl group, dodecyl group and octadecyl group; alkenyl groups having 2 to 6 carbon atoms such as propenyl group, butenyl group, pentenyl group and hexenyl group; ethylidene group, propylidene group and butylidene group Group, pentylidene group, hexylidene group and the like having 2 to 6 carbon atoms; cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, methylcyclohexyl group, cyclooctyl group, dimethylcyclohexyl group, isophorone group, norbornylene group, C 3-10 carbon atoms such as decalin and adamantyl groups Alkyl group; aryl group having 6 to 14 carbon atoms such as phenyl group, tolyl group, xylyl group, naphthyl group, biphenyl-4-yl group, anthryl group, trimethylphenyl group; methylene group, ethylene group, propylene group, butylene Group, pentylene group, hexylene group, heptylene group, octylene group, nonylene group, decylene group, dodecylene group, 2-methylpropylene group, 2-methylhexylene group, tetramethylethylene group, etc. Linear or branched alkylene group; cyclopropylene group, cyclobutylene group, cyclopentylene group, cyclohexylene group, methylene-cyclopentylene-methylene group, ethylene-cyclopentylene-ethylene group, methylene-cyclo Hexylene-methylene group, methylene-trimethylcyclohexyl group, Bisshi Monocyclic or polycyclic cycloalkylene groups having 3 to 20 carbon atoms such as rhohexylene group, methylenebiscyclohexylene group, bicyclo [2.2.1] heptane-2,6-diyl group, and adamantylene group An arylene group having 6 to 20 carbon atoms such as a phenylene group, a tolylene group, a xylylene group, a naphthylene group, a biphenylene group, an anthrylene group or a trimethylphenylene group; a monocyclic group having 3 to 20 carbon atoms such as a methylenebisphenylene group or Examples thereof include an alkylarylene group containing a polycyclic aromatic ring. These groups include various isomers.

In the above formula (2), the hydrocarbon group represented by R ¹ may have a substituent. Examples of the substituent include a hydroxyl group, a halogen atom, a cyano group, a carboxyl group, an alkoxy group, an aryloxy group, an alkylthio group, an arylthio group, and a (meth) acryloyloxy group.

In the above formula (2), n is an integer of 1 or more and 4 or less. Note that n is determined by the valence of R ¹ . When R ¹ is a monovalent group (for example, a cyclohexyl group), n is 1. When R ¹ is a divalent group (for example, cyclohexylene group), n is 2.

  Examples of amine compounds used in the method of the present invention include hexylamine, octylamine, dodecylamine, octadecylamine, 1,4-diaminobutane, 1,5-diaminopentane, 1,6-diaminohexane, 1,8 -Aliphatic amine compounds such as diaminooctane, 1,9-diaminononane, 1,10-diaminodecane, 1,12-diaminododecane, 1,3,6-triaminohexane; 1,3- or 1,4- Diaminocyclohexane, 1,3- or 1,4-bis (aminomethyl) cyclohexane, 2,4′- or 4,4′-diaminodicyclohexylmethane, 2,5-bis (aminomethyl) bicyclo [2,2,1 ] Heptane, 2,6-bis (aminomethyl) bicyclo [2,2,1] heptane, 1-amino-3,3,5-trimethyl Alicyclic amine compounds such as -5- (aminomethyl) -cyclohexane, 3-aminomethyl-3,5,5-trimethyl-1-aminocyclohexane, 4,4'-diamino-2,2'-dicyclohexylpropane 1,3- or 1,4-diaminomethylbenzene, 1,3- or 1,4-diaminobenzene, 2,4′- or 4,4′-diaminodiphenylmethane, 1,5- or 2,6-diamino; Aromatic amine compounds such as naphthalene, 4,4′-diaminobiphenyl, 2,4- or 2,6-diaminotoluene, 2,2-bis (4-aminophenyl) propane and the like can be mentioned.

  The carbonate compound used in the method of the present invention is represented by the following general formula (3).

(In the formula, R ² represents a hydrocarbon group which may have a substituent.)

In the above formula (3), examples of the hydrocarbon group represented by R ² are straight chain having 1 to 20 carbon atoms such as methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, etc. Or a branched alkyl group. The hydrocarbon group represented by R ² is preferably a linear or branched alkyl group having 1 to 6 carbon atoms, more preferably a methyl group or an ethyl group.

In the above formula (3), the hydrocarbon group represented by R ² may have a substituent. Examples of the substituent include halogen atoms such as fluorine atom, chlorine atom, bromine atom and iodine atom, alkoxy groups having 1 to 4 carbon atoms such as methoxyl group, ethoxyl group, propoxyl group and butoxyl group, cyano group, A nitro group etc. are mentioned.

  Examples of carbonate compounds that can be used in the method of the present invention include dimethyl carbonate and diethyl carbonate. These carbonate compounds may be used alone or in admixture of two or more.

  The amount of the carbonate compound used is preferably 1 mol or more and 100 mol or less, more preferably 1 mol or more and 50 mol or less, still more preferably 2 mol or more and 20 mol per mol of the amine compound represented by the above formula (2). The amount is not more than mol, particularly preferably not less than 2 mol and not more than 15 mol, most preferably not less than 2 mol and not more than 10 mol.

  Examples of the enzyme used in the method of the present invention include protease, esterase, lipase and the like. Examples of the enzyme include porcine liver-derived esterase (PLE), porcine liver-derived lipase (PPL), lipase of microorganisms that can be isolated from yeast or bacteria; more preferably, Burkholderia cepacia (Burkholderia cepacia) Lipase originating from (Pseudomonas cepacia) (eg Amano PS (manufactured by Amano Enzyme), etc.), lipase originating from Candida antarctica (eg, Novozym 435 (manufactured by Novozyme) etc.) Lipases originating from Rhizomucor Miehei (for example, Lipozyme RM IM (manufactured by Novozyme), etc.), Thermomyces lanuginosus ( Hermomyces lanuginosus) lipase originating (Lipase TL), lipase (Lipase MM to Mucor miehei the (Mucor Miehei) origin), more preferably used is a lipase originating from Candida antarctica. These enzymes may be used in a natural form, or commercially available products may be used as they are as immobilized enzymes. These enzymes may be used alone or in combination of two or more.

  The enzymes mentioned above as examples can also be used after chemical or physical treatment. For example, after the enzyme is dissolved in a buffer solution (an organic solvent may be present if necessary), the solution is directly or stirred and then freeze-dried. This lyophilization refers to, for example, J. Org. Am. Chem. Soc. 122 (8), 1565-1571 (2000), the aqueous solution or water-containing substance is rapidly frozen at a temperature below the freezing point, and the pressure is reduced below the water vapor pressure of the frozen product to sublimate the water and remove it. It is a method of drying a substance. By such treatment, catalytic activity (reactivity, selectivity, etc.) can be improved.

  In the method of the present invention, the enzyme is preferably immobilized on a fixed bed. The fixed bed is provided with a carrier, and an enzyme is immobilized on the carrier. The fixed bed is preferably installed inside the reaction vessel.

  The amount of the enzyme used is preferably 0.1 mg or more and 1000 mg or less, more preferably 1 mg or more and 200 mg or less, and further preferably 10 mg or more and 100 mg or less with respect to 1 g of the amine compound represented by the above formula (2).

  The method for producing an isocyanate compound of the present invention comprises a step of supplying a carbamate compound together with a carrier gas into a hollow space not containing a solid catalyst and / or a filler, and a step of thermally decomposing the carbamate compound in the hollow space. Have.

  In the method of the present invention, the value (N) obtained by dividing the volume of the hollow space by the total supply amount per unit time of the carbamate compound and the carrier gas is preferably 0.001 or more and 2.0 or less. It is more preferably 0.002 or more and 0.1 or less, further preferably 0.002 or more and 0.04 or less, and particularly preferably 0.004 or more and 0.02 or less.

  The unit of the volume of the hollow space is [milliliter]. The unit of the total supply amount per unit time of the carbamate compound and the carrier gas is [milliliter / minute]. Therefore, the unit of the value (N) obtained by dividing the former by the latter is [minute]. This value (N) is sometimes called the residence time. The total supply amount per unit time of the carbamate compound and the carrier gas is expressed as a volume flow rate of the gas at the thermal decomposition temperature of the carbamate compound.

In the method of the present invention, the total supply amount per unit time of the carbamate compound and the carrier gas satisfies the following relationship.
N = (volume of hollow space [milliliter]) / (total supply amount of carbamate compound and carrier gas [milliliter / min]) = 0.001 to 2.0 [min]

  By setting the total supply amount per unit time of the carbamate compound and the carrier gas within the above range, the pressure loss when supplying the carbamate compound to the hollow space can be reduced. Moreover, it is possible to prevent the hollow space from being blocked by the sequential reaction product. In addition, the carbamate compound can be heated to a predetermined thermal decomposition temperature in a short time.

  The thermal decomposition temperature of the carbamate compound is preferably 450 ° C. or higher and 600 ° C. or lower, more preferably 500 ° C. or higher and 550 ° C. or lower. When the thermal decomposition temperature is lower than 450 ° C., a practical thermal decomposition rate may not be obtained. When the thermal decomposition temperature exceeds 550 ° C., undesirable side reactions such as polymerization of isocyanate compounds may occur.

  The method of the present invention can be carried out, for example, by feeding a carbamate compound into a hollow reaction tube heated from the outside. When the carbamate compound is a solid, it is preferable to heat the carbamate compound in advance to make it liquid. The heating temperature of the hollow reaction tube is preferably 450 ° C. or higher and 600 ° C. or lower, more preferably 500 ° C. or higher and 550 ° C. or lower. By setting the heating temperature of the hollow reaction tube within this range, generation of by-products can be suppressed.

  In the method of the present invention, the inside of the hollow reaction tube may be in a pressurized state or in a reduced pressure state. The inside of the hollow reaction tube may be pressurized as long as the liquid phase is not formed in the heated portion of the hollow reaction tube. In order to prevent a liquid phase from being formed inside the hollow reaction tube, the inside of the hollow reaction tube may be decompressed.

  In the method of the present invention, it is preferable to set the pressure inside the hollow reaction tube so that the pressure at the outlet of the hollow reaction tube becomes a normal pressure. Thereby, the structure of the reaction apparatus can be simplified.

  The reaction time for the thermal decomposition reaction of the carbamate compound is preferably 0.1 second or more and 2.0 seconds or less, and more preferably 0.5 or more and 1.0 seconds or less. By setting the reaction time within this range, the thermal decomposition reaction of the carbamate compound can sufficiently proceed, and the generation of by-products can be suppressed.

  In the method of the present invention, in the presence of an enzyme, the amine compound represented by the general formula (2) and the carbonate compound represented by the general formula (3) are reacted in the presence or absence of a solvent inside the reaction vessel. It is preferable to have the process of supplying the obtained reaction liquid to the said hollow space after making it react under.

  That is, the method of the present invention preferably includes a step of reacting the amine compound represented by the general formula (2) with the carbonate compound represented by the general formula (3). The reaction liquid obtained by this reaction contains a carbamate compound as a raw material. An isocyanate compound can be produced by supplying this reaction liquid to the hollow space and thermally decomposing the carbamate compound contained in the reaction liquid.

The solvent is not particularly limited as long as it does not deactivate the enzyme.
The solvent is preferably at least one selected from the group consisting of aliphatic hydrocarbons, aromatic hydrocarbons, and acyclic ethers.

  Examples of aliphatic hydrocarbons that can be used as the solvent include unsubstituted cycloalkanes having 5 to 10 carbon atoms such as cyclopentane, cyclohexane, cycloheptane, and isopropylcyclohexane; halogens such as chlorocyclopentane and chlorocyclohexane. Examples include substituted cycloalkanes having 5 to 10 carbon atoms. Preferably it is a C5-C10 unsubstituted cycloalkane, More preferably, it is a cyclohexane. These aliphatic hydrocarbons may be used alone or in combination of two or more.

  Examples of aromatic hydrocarbons that can be used as the solvent include benzene, toluene, xylene, mesitylene and the like. Preferably it is toluene or xylene. In addition, these aromatic hydrocarbons may be used independently and may mix and use 2 or more types.

  Examples of the acyclic ether that can be used as the solvent include dialkyl ethers having 2 to 8 carbon atoms such as diethyl ether, t-butyl methyl ether, diisopropyl ether, etc .; carbon atoms such as cyclopentyl methyl ether, cyclopentyl ethyl ether, etc. C5-C18 cycloalkyl alkyl ethers; C7-18 aromatic ethers such as benzyl phenyl ether, benzyl methyl ether, diphenyl ether, di (p-tolyl) ether, dibenzyl ether and the like. Aliphatic ethers are preferred, and diisopropyl ether is more preferred. These acyclic ethers may be used alone or in combination of two or more.

  The amount of the solvent used is preferably 2 mL or more and 200 mL or less, more preferably 2 mL or more and 50 mL or less, and further preferably 5 mL or more and 20 mL or less with respect to 1 g of the amine compound represented by the above formula (2).

The step of reacting the amine compound represented by the general formula (2) and the carbonate compound represented by the general formula (3) can be performed, for example, by the following method (a) or (b).
(A) An amine compound represented by the above formula (2), a carbonate compound represented by the above formula (3), and an enzyme are mixed and reacted with stirring.
(B) An amine compound represented by the above formula (2), a carbonate compound represented by the above formula (3), an enzyme, and a solvent are mixed and reacted while stirring.

  The temperature at which the amine compound and the carbonate compound are reacted is not particularly limited as long as the enzyme does not deactivate, but is preferably 55 ° C. or higher and 90 ° C. or lower, more preferably 60 ° C. or higher and 90 ° C. or lower, and further preferably 65 ° C. It is 90 degrees C or less. In addition, the reaction pressure is not particularly limited, but is preferably normal pressure or reduced pressure.

  In the step of reacting the amine compound and the carbonate compound, the reaction conditions are preferably set in accordance with the characteristics of the enzyme used. The pH of the reaction solution is not particularly limited, but is preferably a pH value of 5 to 9, more preferably a pH value of 6 to 8.5, and even more preferably a pH value of 6.5 to 8.

The step of reacting the amine compound and the carbonate compound may be performed by any apparatus. For example, a general production apparatus such as a reaction vessel, a heating apparatus, or a cooling apparatus can be used.
In the step of reacting the amine compound and the carbonate compound, it is preferable to use an apparatus having a fixed bed on which the enzyme is fixed. The fixed bed is installed inside the reaction vessel. The fixed bed includes a carrier on which an enzyme is fixed.

The reaction solution obtained by reacting the amine compound represented by the above general formula (2) with the carbonate compound represented by the above general formula (3) is used as it is without performing operations such as isolation and purification. It can be used in the thermal decomposition process.
That is, the reaction liquid obtained by reacting the amine compound represented by the general formula (2) and the carbonate compound represented by the general formula (3) is supplied as it is to the hollow reaction tube (hollow space). Can do.

  In addition, before supplying the reaction liquid obtained by making an amine compound and a carbonate compound react to a hollow reaction tube, you may adjust the quantity of the solvent contained in a reaction liquid as needed.

  In particular, when the enzyme is not fixed to the fixed bed, the reaction solution obtained by reacting the amine compound and the carbonate compound is allowed to pass through a filter, and then the reaction solution is supplied to the hollow reaction tube. preferable.

  The amine compound may remain in the reaction solution obtained by reacting the amine compound and the carbonate compound. After the amine compound is consumed substantially completely, the reaction solution is preferably sent to the next pyrolysis step. Thereby, the production | generation of a urea compound can be suppressed.

  The reaction solution obtained by reacting the amine compound represented by the general formula (2) with the carbonate compound represented by the general formula (3) contains a carbamate compound. Specific examples of the carbamate compound are as described above.

  According to the method of the present invention, an isocyanate compound can be produced at a high reaction rate and in a high yield only by thermal decomposition. In addition, according to the method of the present invention, the reaction tube can be prevented from being blocked.

  Examples of isocyanate compounds obtained by the method of the present invention include hexyl isocyanate, octyl isocyanate, dodecyl isocyanate, octadecyl isocyanate, 1,4-diisocyanatobutane, 1,5-diisocyanatopentane, 1,6-diisocyanato. Hexane, 1,8-diisocyanatooctane, 1,9-diisocyanatononane, 1,10-diisocyanatodecane, 1,12-diisocyanatododecane, 1,3,6-triisocyanatohexane, etc. Aliphatic isocyanate compounds; 1,3- or 1,4-diisocyanatocyclohexane, 1,3- or 1,4-bis (isocyanatomethyl) cyclohexane, dicyclohexylmethane 4,4-diisocyanate, dicyclohexylmethane 2,4 '-Diisocyanate, Bisiku [2,2,1] heptane-2,5-diisocyanate, bicyclo [2,2,1] heptane-2,6-diisocyanate, 2,5-bis (isocyanatomethyl) bicyclo [2,2,1] heptane 2,6-bis (isocyanatomethyl) bicyclo [2,2,1] heptane, 1-isocyanato-3,3,5-trimethyl-5- (isocyanatomethyl) -cyclohexane, 4,4′-diisocyanato- Alicyclic isocyanate compounds such as 2,2-dicyclohexylpropane; 1,3- or 1,4-bis (isocyanatomethyl) benzene, 1,3- or 1,4-phenylene diisocyanate, 2,4'- or 4,4′-diphenylmethane diisocyanate, 4,4′-bis (isocyanatomethyl) diphenylmethane, 1,5- or 2,6-diisocyana And aromatic isocyanate compounds such as tonaphthalene, 4,4′-diisocyanatobiphenyl, 2,4- or 2,6-tolylene diisocyanate, and 2,2-bis (4-isocyanatophenyl) propane. . In addition, the substituent couple | bonded with the isocyanate group of these compounds contains various isomers.

  Next, specific examples of the present invention will be described. The present invention is not limited to the following examples. In Examples 1 to 14 and Comparative Example 1, the reaction apparatus shown in FIG. 1 was used. In Examples 15 to 16, the reactor shown in FIG. 2 was used.

  In the following Examples 1 to 16, the conversion rate means the conversion rate of the carbamate compound. A yield means the yield of an isocyanate compound. Selectivity means the selectivity of an isocyanate compound. These can be obtained by the following equations.

  In the following Examples 17 to 30, the conversion rate means the conversion rate of the amine compound. A yield means the yield of an isocyanate compound. Selectivity means the selectivity of an isocyanate compound. These can be obtained by the following equations.

[Example 1]
In Example 1, n-hexyl isocyanate (isocyanate compound) was synthesized according to the following formula.

In Example 1, the apparatus shown in FIG. 1 was used.
The apparatus shown in FIG. 1 includes a reaction hollow tube made of a stainless steel tube having an inner diameter of 0.5 mm. A hollow space is formed inside the hollow reaction tube. The hollow reaction tube is heated to 500 ° C. from the outside by an annular furnace. The heated part of the hollow reaction tube is a pyrolysis zone. The length of the pyrolysis zone is 600 mm.

An inlet is provided above the pyrolysis zone of the hollow reaction tube. A pipe for supplying a carbamate compound as a raw material and a carrier gas is connected to the inlet.
An outlet is provided below the pyrolysis zone of the hollow reaction tube. A pipe for supplying the outlet carrier gas, a trap for collecting the product, and a trap for collecting methanol are connected to the outlet. The product collection trap is heated to 70 ° C and the methanol collection trap is cooled to -78 ° C.

  First, an inlet carrier gas was supplied to the inlet of the hollow reaction tube, and an outlet carrier gas was supplied to the outlet of the hollow reaction tube. Nitrogen was used as the carrier gas.

  After the flow rate of the inlet carrier gas was stabilized at 12 mL / min and the flow rate of the outlet carrier gas was 15 mL / min, methyl n-hexylcarbamate (carbamate compound) was added to the inlet of the hollow reaction tube using a syringe pump to a concentration of 0. It was fed at a flow rate of 1 mL / min. At this time, the residence time of methyl n-hexylcarbamate was 0.1 seconds.

  In Example 1, the value (N) obtained by dividing the volume of the hollow space by the total supply amount per unit time of the carbamate compound and the carrier gas was 0.002 [min].

  The target product (isocyanate compound) collected in the product collection trap was quantified by an internal standard method using gas chromatography.

[Examples 2 to 4 and Comparative Example 1]
In the same manner as in Example 1, n-hexyl isocyanate (isocyanate compound) was synthesized.
In Examples 2 to 4 and Comparative Example 1, various conditions were changed as shown in Table 1 below.

[Example 5]
In Example 5, 1,3-bis (isocyanatomethyl) cyclohexane (isocyanate compound) was synthesized according to the following formula.

In Example 5, the apparatus shown in FIG. 1 was used.
In Example 5, the apparatus shown in FIG. 1 includes a reaction hollow tube made of a stainless steel tube having an inner diameter of 1.0 mm. A hollow space is formed inside the hollow reaction tube. The hollow reaction tube is heated to 550 ° C. from the outside by an annular furnace. The heated part of the hollow reaction tube is a pyrolysis zone. The length of the pyrolysis zone is 1200 mm.

An inlet is provided above the pyrolysis zone of the hollow reaction tube. A pipe for supplying a carbamate compound as a raw material and a carrier gas is connected to the inlet.
An outlet is provided below the pyrolysis zone of the hollow reaction tube. A pipe for supplying the outlet carrier gas, a trap for collecting the product, and a trap for collecting methanol are connected to the outlet. The product collection trap is heated to 70 ° C and the methanol collection trap is cooled to -78 ° C.

  First, an inlet carrier gas was supplied to the inlet of the hollow reaction tube, and an outlet carrier gas was supplied to the outlet of the hollow reaction tube. Nitrogen was used as the carrier gas.

  After the inlet carrier gas flow rate was stabilized at 22 mL / min and the outlet carrier gas flow rate at 70 mL / min, 1,3-bis (methoxycarbonylaminomethyl) cyclohexane (using a syringe pump at the inlet of the hollow reaction tube) Carbamate compound) was fed at a flow rate of 0.1 mL / min. At this time, the residence time of 1,3-bis (methoxycarbonylaminomethyl) cyclohexane was 0.2 seconds. Note that 1,3-bis (methoxycarbonylaminomethyl) cyclohexane was heated to a melting point or higher before being sent into the hollow reaction tube.

  In Example 5, the value (N) obtained by dividing the volume of the hollow space by the total supply amount per unit time of the carbamate compound and the carrier gas was 0.004 [min].

  1,3-bis (isocyanatomethyl) cyclohexane collected in the product collection trap was induced into diurea using diethylamine, and quantified by liquid calibration using an absolute calibration curve method (Table 2).

[Examples 6 to 12]
In the same manner as in Example 5, 1,3-bis (isocyanatomethyl) cyclohexane (isocyanate compound) was synthesized.
In Examples 6 to 12, various conditions were changed as shown in Table 2 below.
In Examples 6-7, the hollow reaction tube was heated to 550 ° C.
In Examples 8 to 11, the hollow reaction tube was heated to 500 ° C.
In Example 12, the hollow reaction tube was heated to 600 ° C.

[Example 13]
In Example 13, isophorone diisocyanate (isocyanate compound) was synthesized according to the following formula.

In Example 13, the apparatus shown in FIG. 1 was used.
In Example 13, the apparatus shown in FIG. 1 includes a reaction hollow tube made of a stainless steel tube having an inner diameter of 1.0 mm. A hollow space is formed inside the hollow reaction tube. The hollow reaction tube is heated to 500 ° C. from the outside by an annular furnace. The heated part of the hollow reaction tube is a pyrolysis zone. The length of the pyrolysis zone is 1200 mm.

An inlet is provided above the pyrolysis zone of the hollow reaction tube. A pipe for supplying a carbamate compound as a raw material and a carrier gas is connected to the inlet.
An outlet is provided below the pyrolysis zone of the hollow reaction tube. A pipe for supplying the outlet carrier gas, a trap for collecting the product, and a trap for collecting methanol are connected to the outlet. The product collection trap is heated to 70 ° C and the methanol collection trap is cooled to -78 ° C.

  First, an inlet carrier gas was supplied to the inlet of the hollow reaction tube, and an outlet carrier gas was supplied to the outlet of the hollow reaction tube. Nitrogen was used as the carrier gas.

  After the flow rate of the inlet carrier gas is stabilized at 10 mL / min and the flow rate of the outlet carrier gas is 70 mL / min, isophorone dicarbamic acid dimethyl ester (carbamate compound) is added to the inlet of the hollow reaction tube by a syringe pump to a value of 0. It was fed at a flow rate of 1 mL / min. At this time, the residence time of isophorone dicarbamic acid dimethyl ester was 1.2 seconds. In addition, the isophorone dicarbamic acid dimethyl ester was heated to the melting point or higher and melted before being fed into the hollow reaction tube.

  In Example 13, the value (N) obtained by dividing the volume of the hollow space by the total supply amount per unit time of the carbamate compound and the carrier gas was 0.02 [min].

  The isophorone diisocyanate collected in the product collection trap was derived into a diurea using diethylamine and quantified by an absolute calibration curve method using liquid chromatography (Table 3).

[Example 14]
In the same manner as in Example 13, isophorone diisocyanate (isocyanate compound) was synthesized.
In Example 14, various conditions were changed as shown in Table 3 below.
In Example 14, the hollow reaction tube was heated to 550 ° C.

[Example 15]
In Example 15, n-hexyl isocyanate (isocyanate compound) was synthesized according to the following formula.

In Example 15, the apparatus shown in FIG. 2 was used.
In Example 15, the apparatus shown in FIG. 2 includes a reaction hollow tube made of a stainless steel tube having an inner diameter of 1.0 mm. A hollow space is formed inside the hollow reaction tube. A partition member is installed inside the hollow space. The partition member is composed of one rod-shaped stainless steel wire having an outer diameter of 0.5 mm (a plurality of stainless steel wires are shown in FIG. 2). The hollow reaction tube is heated to 500 ° C. from the outside by an annular furnace. The heated part of the hollow reaction tube is a pyrolysis zone. The length of the pyrolysis zone is 1200 mm.

An inlet is provided above the pyrolysis zone of the hollow reaction tube. A pipe for supplying a carbamate compound as a raw material and a carrier gas is connected to the inlet.
An outlet is provided below the pyrolysis zone of the hollow reaction tube. A pipe for supplying the outlet carrier gas, a trap for collecting the product, and a trap for collecting methanol are connected to the outlet. The product collection trap is heated to 70 ° C and the methanol collection trap is cooled to -78 ° C.

  First, an inlet carrier gas was supplied to the inlet of the hollow reaction tube, and an outlet carrier gas was supplied to the outlet of the hollow reaction tube. Nitrogen was used as the carrier gas.

  After the flow rate of the inlet carrier gas was stabilized at 15 mL / min and the flow rate of the outlet carrier gas was 70 mL / min, methyl N-hexylcarbamate (carbamate compound) was added to the inlet of the hollow reaction tube by using a syringe pump. It was fed at a flow rate of 1 mL / min. At this time, the residence time of methyl N-hexylcarbamate was 0.6 seconds.

  In Example 15, the value (N) obtained by dividing the volume of the hollow space by the total supply amount per unit time of the carbamate compound and the carrier gas was 0.01 [min].

  The n-hexyl isocyanate collected in the product collection trap was quantified by an internal standard method using gas chromatography (Table 4).

[Example 16]
In the same manner as in Example 15, n-hexyl isocyanate (isocyanate compound) was synthesized.
In Example 16, various conditions were changed as shown in Table 4 below.
In Example 16, a hollow reaction tube made of a stainless steel tube having an inner diameter of 1.0 mm was used. A hollow space is formed inside the hollow reaction tube. A partition member is installed inside the hollow space. The partition member is composed of ten stainless steel wires having an outer diameter of 0.1 mm (FIG. 2).

[Example 17]
In Example 17, n-hexyl isocyanate (isocyanate compound) was synthesized.
First, in the presence of an enzyme, an amine compound represented by the above formula (2) and a carbonate compound represented by the above formula (3) were reacted in the presence of a solvent inside the reaction vessel (first step). .
Next, the reaction solution obtained in the first step was supplied to the hollow reaction tube (second step).
N-hexyl isocyanate was synthesize | combined by implementing a 1st process and a 2nd process continuously.

(First step)
First, a glass container having a volume of 200 mL equipped with a stirrer, a temperature control device, and an upper cooling device was prepared. In this container, 10 g (99 mmol) of n-hexylamine, 53 g (593 mmol) of dimethyl carbonate, 100 mL of toluene, and 0.5 g of lipase derived from Candida antarctica (Novozym 435 (trade name); manufactured by Novozyme) ). And these were made to react for 22 hours, mixing and stirring at 70 degreeC inside a container. After completion of the reaction, the obtained reaction liquid (hereinafter referred to as “reaction liquid 1”) was passed through a filter, and then the reaction liquid 1 was directly transferred to the apparatus shown in FIG.

(Second step)
In Example 17, the apparatus shown in FIG. 1 includes a reaction hollow tube made of a stainless steel tube having an inner diameter of 1.0 mm. A hollow space is formed inside the hollow reaction tube. The hollow reaction tube is heated to 500 ° C. from the outside by an annular furnace. The heated part of the hollow reaction tube is a pyrolysis zone. The length of the pyrolysis zone is 2400 mm.

An inlet is provided above the pyrolysis zone of the hollow reaction tube. A pipe for supplying the reaction liquid 1 and the carrier gas is connected to the inlet.
An outlet is provided below the pyrolysis zone of the hollow reaction tube. A pipe for supplying the outlet carrier gas, a trap for collecting the product, and a trap for collecting methanol are connected to the outlet. The product collection trap is heated to 70 ° C and the methanol collection trap is cooled to -78 ° C.

  First, an inlet carrier gas was supplied to the inlet of the hollow reaction tube, and an outlet carrier gas was supplied to the outlet of the hollow reaction tube. Nitrogen was used as the carrier gas.

  After the inlet carrier gas flow rate is stabilized at 17 mL / min and the outlet carrier gas flow rate is 10 mL / min, the reaction solution 1 is fed into the inlet of the hollow reaction tube at a flow rate of 0.1 mL / min using a syringe pump. It is. At this time, the residence time of the reaction liquid 1 was 1.1 seconds.

  The reaction solution 1 contains a carbamate compound that is a reaction product of n-hexylamine and dimethyl carbonate.

  In Example 17, the value (N) obtained by dividing the volume of the hollow space by the total supply amount per unit time of the carbamate compound and the carrier gas was 0.019 [min].

  In addition, n-hexyl isocyanate collected in the product collection trap was quantified by an internal standard method using gas chromatography. The results are shown in Table 5.

[Examples 18 to 19]
In the same manner as in Example 17, n-hexyl isocyanate (isocyanate compound) was synthesized.
In Examples 18 to 19, various conditions were changed as shown in Table 5 below.

[Example 20]
In Example 20, n-hexyl isocyanate (isocyanate compound) was synthesized.
First, in the presence of an enzyme, an amine compound represented by the above formula (2) and a carbonate compound represented by the above formula (3) were reacted in the presence of a solvent inside the reaction vessel (first step). .
Next, the reaction solution obtained in the first step was supplied to the hollow reaction tube (second step).
N-hexyl isocyanate was synthesize | combined by implementing a 1st process and a 2nd process continuously.

(First step)
First, a glass container having a volume of 200 mL equipped with a stirrer, a temperature control device, and an upper cooling device was prepared. In this container, 10 g (99 mmol) of n-hexylamine, 53 g (593 mmol) of dimethyl carbonate, 100 mL of toluene, and 0.5 g of lipase derived from Candida antarctica (Novozym 435 (trade name); manufactured by Novozyme) ). And these were made to react for 22 hours, mixing and stirring at 70 degreeC inside a container. After completion of the reaction, the obtained reaction solution (hereinafter referred to as “reaction solution 2”) was passed through a filter, and then the reaction solution 2 was directly transferred to the apparatus shown in FIG.

(Second step)
In Example 20, the apparatus shown in FIG. 1 includes a reaction hollow tube made of a stainless steel tube having an inner diameter of 1.0 mm. A hollow space is formed inside the hollow reaction tube. The hollow reaction tube is heated to 550 ° C. from the outside by an annular furnace. The heated part of the hollow reaction tube is a pyrolysis zone. The length of the pyrolysis zone is 3600 mm.

An inlet is provided above the pyrolysis zone of the hollow reaction tube. A pipe for supplying the reaction solution 2 and the carrier gas is connected to the inlet.
An outlet is provided below the pyrolysis zone of the hollow reaction tube. A pipe for supplying the outlet carrier gas, a trap for collecting the product, and a trap for collecting methanol are connected to the outlet. The product collection trap is heated to 70 ° C and the methanol collection trap is cooled to -78 ° C.

  First, an inlet carrier gas was supplied to the inlet of the hollow reaction tube, and an outlet carrier gas was supplied to the outlet of the hollow reaction tube. Nitrogen was used as the carrier gas.

  After the inlet carrier gas flow rate is stabilized at 17 mL / min and the outlet carrier gas flow rate is 10 mL / min, the reaction solution 2 is fed into the hollow reaction tube inlet at a flow rate of 0.1 mL / min using a syringe pump. It is. At this time, the residence time of the reaction liquid 2 was 1.6 seconds.

  The reaction liquid 2 contains a carbamate compound that is a reaction product of n-hexylamine and dimethyl carbonate.

  In Example 20, the value (N) obtained by dividing the volume of the hollow space by the total supply amount per unit time of the carbamate compound and the carrier gas was 0.026 [min].

  In addition, n-hexyl isocyanate collected in the product collection trap was quantified by an internal standard method using gas chromatography. The results are shown in Table 6.

[Examples 21 to 22]
In the same manner as in Example 20, n-hexyl isocyanate (isocyanate compound) was synthesized.
In Examples 21 to 22, various conditions were changed as shown in Table 6 below.

In Example 20, the liquid feeding amount in the second step was set to 0.1 mL / min.
In Example 21, the liquid feeding amount in the second step was set to 0.5 mL / min.
In Example 22, the liquid feeding amount in the second step was set to 1.0 mL / min.
The amount of liquid fed in the second step means the amount of liquid fed to the hollow reaction tube of the reaction liquid 2.
The liquid feeding amount in the second step can be rephrased as “substrate solution feeding amount”.

[Example 23]
In Example 23, n-hexyl isocyanate (isocyanate compound) was synthesized.
First, in the presence of an enzyme, an amine compound represented by the above formula (2) and a carbonate compound represented by the above formula (3) were reacted in the presence of a solvent inside the reaction vessel (first step). .
Next, the reaction solution obtained in the first step was supplied to the hollow reaction tube (second step).
N-hexyl isocyanate was synthesize | combined by implementing a 1st process and a 2nd process continuously.

(First step)
First, a glass container having a volume of 200 mL equipped with a stirrer, a temperature control device, and an upper cooling device was prepared. In this container, 10 g (99 mmol) of n-hexylamine, 53 g (593 mmol) of dimethyl carbonate, 100 mL of toluene, and 0.5 g of lipase derived from Candida antarctica (Novozym 435 (trade name); manufactured by Novozyme) ). And these were made to react for 22 hours, mixing and stirring at 70 degreeC inside a container. After completion of the reaction, the obtained reaction liquid (hereinafter referred to as “reaction liquid 3”) was passed through a filter. Subsequently, 20 mL of toluene was passed through the filter. Thereafter, the reaction solution 3 and toluene were directly transferred to the apparatus shown in FIG.

(Second step)
In Example 23, the apparatus shown in FIG. 1 includes a reaction hollow tube made of a stainless steel tube having an inner diameter of 1.0 mm. A hollow space is formed inside the hollow reaction tube. The hollow reaction tube is heated to 500 ° C. from the outside by an annular furnace. The heated part of the hollow reaction tube is a pyrolysis zone. The length of the pyrolysis zone is 1200 mm.

An inlet is provided above the pyrolysis zone of the hollow reaction tube. A pipe for supplying the reaction solution 3 and the carrier gas is connected to the inlet.
An outlet is provided below the pyrolysis zone of the hollow reaction tube. A pipe for supplying the outlet carrier gas, a trap for collecting the product, and a trap for collecting methanol are connected to the outlet. The product collection trap is heated to 70 ° C and the methanol collection trap is cooled to -78 ° C.

  First, an inlet carrier gas was supplied to the inlet of the hollow reaction tube, and an outlet carrier gas was supplied to the outlet of the hollow reaction tube. Nitrogen was used as the carrier gas.

  After the inlet carrier gas flow rate is stabilized at 17 mL / min and the outlet carrier gas flow rate is 10 mL / min, the reaction liquid 3 is fed into the hollow reaction tube inlet at a flow rate of 0.1 mL / min using a syringe pump. It is. At this time, the residence time of the reaction liquid 3 was 0.6 second.

  The reaction solution 3 contains a carbamate compound that is a reaction product of n-hexylamine and dimethyl carbonate.

  In Example 23, the value (N) obtained by dividing the volume of the hollow space by the total supply amount per unit time of the carbamate compound and the carrier gas was 0.009 [min].

  In addition, n-hexyl isocyanate collected in the product collection trap was quantified by an internal standard method using gas chromatography. As a result, the conversion rate was 100 mol%, the yield of n-hexyl isocyanate was 87 mol%, and the selectivity was 87 mol%.

[Example 24]
In Example 24, n-hexyl isocyanate (isocyanate compound) was synthesized.
First, in the presence of an enzyme, an amine compound represented by the above formula (2) and a carbonate compound represented by the above formula (3) were reacted in the presence of a solvent inside the reaction vessel (first step). .
Next, the reaction solution obtained in the first step was supplied to the hollow reaction tube (second step).
N-hexyl isocyanate was synthesize | combined by implementing a 1st process and a 2nd process continuously.

(First step)
First, a glass container having a volume of 100 mL equipped with a stirring device, a temperature control device, and an upper cooling device was prepared. In this container, 5 g (49 mmol) of n-hexylamine, 27 g (296 mmol) of dimethyl carbonate, 50 mL of toluene, and 0.25 g of lipase derived from Candida antarctica (Novozym 435 (trade name); manufactured by Novozyme) ). And these were made to react for 7 hours, mixing and stirring at 70 degreeC inside a container. After completion of the reaction, the obtained reaction liquid (hereinafter referred to as “reaction liquid 4”) was passed through a filter, and then the reaction liquid 4 was directly transferred to the apparatus shown in FIG.

(Second step)
In Example 24, the apparatus shown in FIG. 1 includes a reaction hollow tube made of a stainless steel tube having an inner diameter of 1.0 mm. A hollow space is formed inside the hollow reaction tube. The hollow reaction tube is heated to 550 ° C. from the outside by an annular furnace. The heated part of the hollow reaction tube is a pyrolysis zone. The length of the pyrolysis zone is 2400 mm.

An inlet is provided above the pyrolysis zone of the hollow reaction tube. A pipe for supplying the reaction solution 4 and the carrier gas is connected to the inlet.
An outlet is provided below the pyrolysis zone of the hollow reaction tube. A pipe for supplying the outlet carrier gas, a trap for collecting the product, and a trap for collecting methanol are connected to the outlet. The product collection trap is heated to 70 ° C and the methanol collection trap is cooled to -78 ° C.

  First, an inlet carrier gas was supplied to the inlet of the hollow reaction tube, and an outlet carrier gas was supplied to the outlet of the hollow reaction tube. Nitrogen was used as the carrier gas.

  After the inlet carrier gas flow rate is stabilized at 17 mL / min and the outlet carrier gas flow rate is 10 mL / min, the reaction liquid 4 is fed into the hollow reaction tube inlet at a flow rate of 0.1 mL / min using a syringe pump. It is. At this time, the residence time of the reaction solution 4 was 1.1 seconds.

  In addition, the reaction liquid 4 contains a carbamate compound that is a reaction product of n-hexylamine and dimethyl carbonate.

  In Example 24, the value (N) obtained by dividing the volume of the hollow space by the total supply amount per unit time of the carbamate compound and the carrier gas was 0.018 [min].

  In addition, n-hexyl isocyanate collected in the product collection trap was quantified by an internal standard method using gas chromatography. The results are shown in Table 7 below.

[Example 25]
In the same manner as in Example 24, n-hexyl isocyanate (isocyanate compound) was synthesized.
In Example 25, various conditions were changed as shown in Table 7 below.

[Example 26]
In Example 26, 1,3-bis (isocyanatomethyl) cyclohexane (isocyanate compound) was synthesized.
First, in the presence of an enzyme, an amine compound represented by the above formula (2) and a carbonate compound represented by the above formula (3) were reacted in the presence of a solvent inside the reaction vessel (first step). .
Next, the reaction solution obtained in the first step was supplied to the hollow reaction tube (second step).
1,3-bis (isocyanatomethyl) cyclohexane was synthesized by continuously performing the first step and the second step.

(First step)
First, a glass container having a volume of 200 mL equipped with a stirrer, a temperature control device, and an upper cooling device was prepared. In this container, 10 g (70 mmol) of 1,3-bis (aminomethyl) cyclohexane, 38 g (422 mmol) of dimethyl carbonate, 100 mL of toluene, and 1.0 g of lipase derived from Candida antarctica (Novozym 435 (product) Name); manufactured by Novozyme). And these were made to react for 25 hours, mixing and stirring at 70 degreeC inside a container. After completion of the reaction, the obtained reaction liquid (hereinafter referred to as “reaction liquid 5”) was passed through a filter. Subsequently, 20 mL of toluene was passed through the filter. Thereafter, the reaction solution 5 and toluene were directly transferred to the apparatus shown in FIG.

(Second step)
In Example 26, the apparatus shown in FIG. 1 includes a reaction hollow tube made of a stainless steel tube having an inner diameter of 1.0 mm. A hollow space is formed inside the hollow reaction tube. The hollow reaction tube is heated to 550 ° C. from the outside by an annular furnace. The heated part of the hollow reaction tube is a pyrolysis zone. The length of the pyrolysis zone is 2400 mm.

An inlet is provided above the pyrolysis zone of the hollow reaction tube. A pipe for supplying the reaction solution 5 and the carrier gas is connected to the inlet.
An outlet is provided below the pyrolysis zone of the hollow reaction tube. A pipe for supplying the outlet carrier gas, a trap for collecting the product, and a trap for collecting methanol are connected to the outlet. The product collection trap is heated to 70 ° C and the methanol collection trap is cooled to -78 ° C.

  First, an inlet carrier gas was supplied to the inlet of the hollow reaction tube, and an outlet carrier gas was supplied to the outlet of the hollow reaction tube. Nitrogen was used as the carrier gas.

  After the inlet carrier gas flow rate is stabilized at 17 mL / min and the outlet carrier gas flow rate is 10 mL / min, the reaction solution 5 is fed into the hollow reaction tube inlet at a flow rate of 0.1 mL / min using a syringe pump. It is. At this time, the residence time of the reaction solution 5 was 1.1 seconds.

  In addition, the reaction liquid 5 contains a carbamate compound that is a reaction product of 1,3-bis (aminomethyl) cyclohexane and dimethyl carbonate.

  In Example 26, the value (N) obtained by dividing the volume of the hollow space by the total supply amount per unit time of the carbamate compound and the carrier gas was 0.018 [min].

  The 1,3-bis (isocyanatomethyl) cyclohexane collected in the product collection trap was derived into a diurea using diethylamine, and quantified by an absolute calibration curve method using liquid chromatography. The results are shown in Table 8 below.

[Example 27]
In the same manner as in Example 26, 1,3-bis (isocyanatomethyl) cyclohexane (isocyanate compound) was synthesized.
In Example 27, various conditions were changed as shown in Table 8 below.

[Example 28]
In Example 28, 1,3-bis (isocyanatomethyl) cyclohexane (isocyanate compound) was synthesized.
First, in the presence of an enzyme, an amine compound represented by the above formula (2) and a carbonate compound represented by the above formula (3) were reacted in the presence of a solvent inside the reaction vessel (first step). .
Next, the reaction solution obtained in the first step was supplied to the hollow reaction tube (second step).
1,3-bis (isocyanatomethyl) cyclohexane was synthesized by continuously performing the first step and the second step.

(First step)
First, a glass container having a volume of 200 mL equipped with a stirrer, a temperature control device, and an upper cooling device was prepared. In this container, 10 g (70 mmol) of 1,3-bis (aminomethyl) cyclohexane, 38 g (422 mmol) of dimethyl carbonate, 100 mL of toluene, and 1.0 g of lipase derived from Candida antarctica (Novozym 435 (product) Name); manufactured by Novozyme). And these were made to react for 48 hours, mixing and stirring at 70 degreeC inside a container. After completion of the reaction, the obtained reaction liquid (hereinafter referred to as “reaction liquid 6”) was passed through a filter. Subsequently, 20 mL of toluene was passed through the filter. Thereafter, the reaction solution 6 and toluene were directly transferred to the apparatus shown in FIG.

(Second step)
In Example 28, the apparatus shown in FIG. 1 includes a reaction hollow tube made of a stainless steel tube having an inner diameter of 1.0 mm. A hollow space is formed inside the hollow reaction tube. The hollow reaction tube is heated to 600 ° C. from the outside by an annular furnace. The heated part of the hollow reaction tube is a pyrolysis zone. The length of the pyrolysis zone is 3600 mm.

An inlet is provided above the pyrolysis zone of the hollow reaction tube. A pipe for supplying the reaction liquid 6 and the carrier gas is connected to the inlet.
An outlet is provided below the pyrolysis zone of the hollow reaction tube. A pipe for supplying the outlet carrier gas, a trap for collecting the product, and a trap for collecting methanol are connected to the outlet. The product collection trap is heated to 70 ° C and the methanol collection trap is cooled to -78 ° C.

  First, an inlet carrier gas was supplied to the inlet of the hollow reaction tube, and an outlet carrier gas was supplied to the outlet of the hollow reaction tube. Nitrogen was used as the carrier gas.

  After the inlet carrier gas flow rate is stabilized at 17 mL / min and the outlet carrier gas flow rate is 50 mL / min, the reaction liquid 6 is fed into the hollow reaction tube inlet at a flow rate of 0.5 mL / min using a syringe pump. It is. At this time, the residence time of the reaction liquid 6 was 0.5 second.

  Note that the reaction solution 6 contains a carbamate compound that is a reaction product of 1,3-bis (aminomethyl) cyclohexane and dimethyl carbonate.

  In Example 28, the value (N) obtained by dividing the volume of the hollow space by the total supply amount per unit time of the carbamate compound and the carrier gas was 0.008 [min].

  The 1,3-bis (isocyanatomethyl) cyclohexane collected in the product collection trap was derived into a diurea using diethylamine, and quantified by an absolute calibration curve method using liquid chromatography. The results are shown in Table 9 below.

[Example 29]
In the same manner as in Example 28, 1,3-bis (isocyanatomethyl) cyclohexane (isocyanate compound) was synthesized.
In Example 29, various conditions were changed as shown in Table 9 below.

[Example 30]
In Example 30, n-hexyl isocyanate (isocyanate compound) was synthesized.
First, in the presence of an enzyme, an amine compound represented by the above formula (2) and a carbonate compound represented by the above formula (3) were reacted in the presence of a solvent inside the reaction vessel (first step). .
Next, the reaction solution obtained in the first step was supplied to the hollow reaction tube (second step).
N-hexyl isocyanate was synthesize | combined by implementing a 1st process and a 2nd process continuously.

(First step)
First, a PFA (perfluoroalkoxy fluororesin) tube having an inner diameter of 1.6 mm and a length of 550 mm was prepared. Inside this tube, a fixed bed to which 0.3 g of lipase derived from Candida antarctica (Novozym 435 (trade name); manufactured by Novozyme) is fixed. The tube is heated to 80 ° C. To this heated tube, a toluene solution of 7% by mass of n-hexylamine and 36% by mass of dimethyl carbonate was fed using a syringe pump at a flow rate of 0.1 mL / min. Thereby, n-hexylamine and dimethyl carbonate were reacted. The reaction liquid obtained by this reaction (hereinafter referred to as “reaction liquid 7”) was directly transferred to the apparatus shown in FIG.

(Second step)
In Example 30, the apparatus shown in FIG. 1 includes a reaction hollow tube made of a stainless steel tube having an inner diameter of 1.0 mm. A hollow space is formed inside the hollow reaction tube. The hollow reaction tube is heated to 550 ° C. from the outside by an annular furnace. The heated part of the hollow reaction tube is a pyrolysis zone. The length of the pyrolysis zone is 1200 mm.

An inlet is provided above the pyrolysis zone of the hollow reaction tube. A pipe for supplying the reaction liquid 7 and the carrier gas is connected to the inlet.
An outlet is provided below the pyrolysis zone of the hollow reaction tube. A pipe for supplying the outlet carrier gas, a trap for collecting the product, and a trap for collecting methanol are connected to the outlet. The product collection trap is heated to 70 ° C and the methanol collection trap is cooled to -78 ° C.

  First, an inlet carrier gas was supplied to the inlet of the hollow reaction tube, and an outlet carrier gas was supplied to the outlet of the hollow reaction tube. Nitrogen was used as the carrier gas.

  After the inlet carrier gas flow rate is stabilized at 13 mL / min and the outlet carrier gas flow rate at 10 mL / min, the reaction liquid 7 is fed into the hollow reaction tube inlet at a flow rate of 0.1 mL / min using a syringe pump. It is. At this time, the residence time of the reaction liquid 7 was 0.6 second.

  In addition, the reaction liquid 7 contains a carbamate compound that is a reaction product of n-hexylamine and dimethyl carbonate.

  In Example 30, the value (N) obtained by dividing the volume of the hollow space by the total supply amount per unit time of the carbamate compound and the carrier gas was 0.01 [min].

  In addition, n-hexyl isocyanate collected in the product collection trap was quantified by an internal standard method using gas chromatography. The results are shown in Table 10 below.

[Example 31]
In the same manner as in Example 30, n-hexyl isocyanate (isocyanate compound) was synthesized.
In Example 31, various conditions were changed as shown in Table 10 below.

[Example 32]
In Example 32, n-hexyl isocyanate (isocyanate compound) was synthesized.
First, in the presence of an enzyme, the amine compound represented by the above formula (2) and the carbonate compound represented by the above formula (3) were reacted inside the reaction vessel (first step).
Next, the reaction solution obtained in the first step was supplied to the hollow reaction tube (second step).
N-hexyl isocyanate was synthesize | combined by implementing a 1st process and a 2nd process continuously.

(First step)
First, a PFA (perfluoroalkoxy fluororesin) tube having an inner diameter of 1.6 mm and a length of 550 mm was prepared. Inside this tube, a fixed bed to which 0.3 g of lipase derived from Candida antarctica (Novozym 435 (trade name); manufactured by Novozyme) is fixed. The tube is heated to 80 ° C. A solution of 10% by mass of n-hexylamine and 90% by mass of dimethyl carbonate was fed into the heated tube at a flow rate of 0.1 mL / min using a syringe pump. Thereby, n-hexylamine and dimethyl carbonate were reacted. The reaction liquid obtained by this reaction (hereinafter referred to as “reaction liquid 8”) was directly transferred to the apparatus shown in FIG.

(Second step)
In Example 32, the apparatus shown in FIG. 1 includes a reaction hollow tube made of a stainless steel tube having an inner diameter of 1.0 mm. A hollow space is formed inside the hollow reaction tube. The hollow reaction tube is heated to 600 ° C. from the outside by an annular furnace. The heated part of the hollow reaction tube is a pyrolysis zone. The length of the pyrolysis zone is 1200 mm.

An inlet is provided above the pyrolysis zone of the hollow reaction tube. A pipe for supplying the reaction solution 8 and the carrier gas is connected to the inlet.
An outlet is provided below the pyrolysis zone of the hollow reaction tube. A pipe for supplying the outlet carrier gas, a trap for collecting the product, and a trap for collecting methanol are connected to the outlet. The product collection trap is heated to 70 ° C and the methanol collection trap is cooled to -78 ° C.

  First, an inlet carrier gas was supplied to the inlet of the hollow reaction tube, and an outlet carrier gas was supplied to the outlet of the hollow reaction tube. Nitrogen was used as the carrier gas.

  After the inlet carrier gas flow rate is stabilized at 17 mL / min and the outlet carrier gas flow rate is 10 mL / min, the reaction liquid 8 is fed into the hollow reaction tube inlet at a flow rate of 0.1 mL / min using a syringe pump. It is. At this time, the residence time of the reaction liquid 8 was 0.5 second.

  The reaction solution 8 contains a carbamate compound that is a reaction product of n-hexylamine and dimethyl carbonate.

  In Example 32, the value (N) obtained by dividing the volume of the hollow space by the total supply amount per unit time of the carbamate compound and the carrier gas was 0.008 [min].

  In addition, n-hexyl isocyanate collected in the product collection trap was quantified by an internal standard method using gas chromatography. As a result, the conversion was 94 mol%, the yield of n-hexyl isocyanate was 69 mol%, and the selectivity was 73 mol%.

In the above examples, the isocyanate compound could be continuously produced at a high reaction rate by reacting the amine compound and the carbonate compound and supplying the obtained reaction solution to a heated hollow reaction tube. .
In particular, in Examples 19, 20, 21 and 29, the selectivity and yield were high.

  According to the present invention, when an isocyanate compound is produced, the reaction tube can be prevented from being blocked. Moreover, an isocyanate compound can be produced at a high reaction rate and in a high yield only by thermal decomposition.

Claims (7)

A method for producing an isocyanate compound, comprising:
Supplying a carbamate compound together with a carrier gas into a hollow space not containing a solid catalyst and / or packing;
Thermally decomposing the carbamate compound in the hollow space,
The volume of the hollow space, wherein the carbamate compound and the total quantity supplied divided by the per unit time of the carrier gas (N) is state, and are 0.001 to 2,
After reacting an amine compound represented by the following general formula (2) and a carbonate compound represented by the following general formula (3) in the presence of an enzyme, in the presence or absence of a solvent, inside the reaction vessel And a step of supplying the obtained reaction liquid to the hollow space,
The method for producing an isocyanate compound, wherein the solvent is at least one selected from the group consisting of aliphatic hydrocarbons, aromatic hydrocarbons, and acyclic ethers.

(In the formula, R ¹ represents a hydrocarbon group which may have a substituent. N represents an integer of 1 or more and 4 or less.)

(In the formula, R ² represents a hydrocarbon group which may have a substituent.)   The method for producing an isocyanate compound according to claim 1, wherein the carbamate compound is thermally decomposed at a temperature of 450 ° C or higher and 600 ° C or lower. The manufacturing method of the isocyanate compound of Claim 1 or Claim 2 whose said carbamate compound is a compound shown by following General formula (1).

(In the formula, R ¹ and R ² represent a hydrocarbon group. R ¹ and R ² may be the same as or different from each other. R ¹ and R ² may have a substituent. N is an integer of 1 or more and 4 or less. The manufacturing method of the isocyanate compound of any one of Claims 1-3 whose said isocyanate compound is a compound shown by following General formula (4).

(In the formula, R ¹ represents a hydrocarbon group which may have a substituent. N represents an integer of 1 or more and 4 or less.) The method for producing an isocyanate compound according to any one of claims 1 to 4, wherein the aromatic compound is toluene or xylene. The method for producing an isocyanate compound according to any one of claims 1 to 5, wherein a fixed bed to which the enzyme is fixed is installed inside the reaction vessel. The method for producing an isocyanate compound according to any one of claims 1 to 6, wherein the reaction solution is passed through a filter and then supplied to the hollow space.