JP6060902B2 - Method for producing isocyanate compound - Google Patents

Description

  The present invention relates to a novel production method for producing an isocyanate compound directly or continuously from an amine compound and a carbonate compound, without isolating and purifying a carbamate compound produced as an intermediate, and further by this method. It relates to the catalyst used. Furthermore, the present invention relates to a novel method for producing an isocyanate compound from a carbamate compound, and further relates to a catalyst used in the method.

  Isocyanate compounds are useful compounds that are widely used, for example, as raw materials for producing urethane, pharmaceuticals, agricultural chemicals, and the like. Conventionally, an isocyanate compound has been industrially produced from a reaction between an amine and phosgene (see, for example, Patent Document 1). However, phosgene is extremely toxic and handling thereof is complicated. Furthermore, there are various inconveniences such as by-production of a large amount of hydrogen chloride that corrodes the apparatus, and an industrial production method of an isocyanate compound instead of this has been strongly desired.

  On the other hand, the manufacturing method of the isocyanate compound which does not use phosgene has been proposed recently. Many of them are independently studied to produce a carbamate compound from an amine compound and a carbonate compound, and to produce an isocyanate compound by decomposing the carbamate compound.

  For example, as a method for producing an isocyanate compound from a carbamate compound, a method of decomposing a carbamate compound using an organotin catalyst and a solid acid catalyst in combination in a liquid phase has been proposed (for example, Patent Document 2). Further, in the gas phase, the carbamate compound is decomposed using a sintered body of transition metal oxide or a sintered body of oxide of at least one element selected from group IIIa, IVa and Va elements. A method has been proposed (for example, Patent Documents 3 and 4). However, these patent documents do not cover a method for producing a carbamate compound or a series of methods for obtaining an isocyanate compound from a carbamate compound starting material.

  Under such circumstances, it has been desired to propose a method for producing an isocyanate compound directly or continuously from an amine compound and a carbonate compound.

Some attempts have been made to produce an isocyanate compound directly or continuously by combining the production of a carbamate compound and the production of an isocyanate compound, as shown below.
(1) A method of synthesizing a carbamate 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).
(2) A method of synthesizing a carbamate from an amine compound and dialkyl carbonate in the presence of 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, And Patent Documents 6 and 7).
(3) A method of synthesizing carbamic acid phenyl ester from an amine compound and diphenyl carbonate and obtaining an isocyanate compound by thermal decomposition (see, for example, Patent Document 8).

Japanese Patent Laid-Open No. 11-310566 JP 2004-262892 A JP-A-5-18414 JP-A-5-18415 JP 2003-252846 A International Publication No. 2008/084824 International Publication No. 2009/139062 International Publication No. 2009/139061

  However, in the methods of Patent Documents 5 to 8 described above, a plurality of by-products are generated, so that an operation for removing them is required, and the state of the reaction apparatus in each reaction must be managed more strictly. There was a problem. Therefore, there has been a demand for an efficient and productive method for producing an isocyanate compound directly or continuously by a simple operation that does not require any special operation when combining such reactions.

  An object of the present invention is to directly or continuously use a simple method without causing a decrease in yield while maintaining a high reaction rate, starting from reacting an amine compound with a carbonate compound. It is to provide a method for obtaining an isocyanate compound.

（式中、
Ｒ^１は、置換基を有していても良い炭化水素基を示し、
ｎは、１〜４の整数を示す）で示されるアミン化合物と、一般式（２）：

（式中、Ｒ^２は、互い独立して、置換基を有していても良い炭化水素基を示す）で示されるカーボネート化合物とを反応させる工程；並びに
（Ｂ）（Ｂ１）工程（Ａ）の反応生成物を、アルカリ金属化合物及びアルカリ土類金属化合物からなる群より選択される少なくとも１種の金属化合物が担体に担持された触媒と、液相で接触させる工程、あるいは
（Ｂ２）工程（Ａ）の反応生成物を、アルカリ金属化合物及びアルカリ土類金属化合物からなる群より選択される少なくとも１種の金属化合物が担体に担持された触媒と、及び／又は多孔質シリカと、気相で接触させる工程
を含む、一般式（３）：

（式中、Ｒ^１及びｎは、前記と同義である）
で示されるイソシアネート化合物の製造方法に関する。
本発明２は、工程（Ａ）における酵素が、担体に固定化された固定化酵素である、本発明１のイソシアネート化合物の製造方法に関する。
本発明３は、前記固定化酵素が、固定床として反応容器に内挿されている、本発明１のイソシアネート化合物の製造方法に関する。
本発明４は、工程（Ａ）の反応を、反応に不活性な溶媒の存在下で行なう、本発明１〜３のいずれかのイソシアネート化合物の製造方法に関する。
本発明５は、前記溶媒が、脂肪族溶媒、芳香族溶媒及びエーテル溶媒からなる群より選択される少なくとも１種の溶媒である、本発明４のイソシアネート化合物の製造方法に関する。
本発明６は、工程（Ａ）の反応生成物がカルバメート化合物を含む、本発明１〜５のいずれかのイソシアネート化合物の製造方法に関する。
本発明７は、工程（Ｂ）が、工程（Ｂ１）である、本発明１〜６のいずれかのイソシアネート化合物の製造方法に関する。
本発明８は、工程（Ｂ１）における触媒が、焼成体である、本発明７のイソシアネート化合物の製造方法に関する。
本発明９は、工程（Ｂ１）における触媒が、アルカリ金属化合物及びアルカリ土類金属化合物からなる群より選択される少なくとも１種の水溶液に担体を含浸させ、次いで乾固及び／又は濾過し、得られた固体を焼成した焼成体である、本発明８のイソシアネート化合物の製造方法に関する。
本発明１０は、前記金属化合物の水溶液が、硝酸塩及び塩化物からなる群より選択される少なくとも１種の化合物の水溶液である、本発明９のイソシアネート化合物の製造方法に関する。
本発明１１は、前記金属化合物の水溶液が、リチウム化合物、カルシウム化合物及びマグネシウム化合物からなる群より選択される少なくとも１種の化合物の水溶液である、本発明９又は１０のイソシアネート化合物の製造方法に関する。
本発明１２は、前記金属化合物の水溶液が、硝酸リチウム及び／又は硝酸カルシウムの水溶液である、本発明９〜１１のいずれかのイソシアネート化合物の製造方法に関する。
本発明１３は、工程（Ｂ）が、工程（Ｂ２）である、本発明１〜６のいずれかのイソシアネート化合物の製造方法に関する。
本発明１４は、工程（Ｂ２）において、アルカリ金属化合物及びアルカリ土類金属化合物からなる群より選択される少なくとも１種の金属化合物が担体に担持された触媒を用いる、本発明１３のイソシアネート化合物の製造方法に関する
本発明１５は、前記触媒が、焼成体である、本発明１４のイソシアネート化合物の製造方法に関する。
本発明１６は、前記触媒が、アルカリ金属化合物及びアルカリ土類金属化合物からなる群より選択される少なくとも１種の水溶液に担体を含浸させ、次いで乾固及び／又は濾過し、得られた固体を焼成した焼成体である、本発明１５のイソシアネート化合物の製造方法に関する。
本発明１７は、前記金属化合物の水溶液が、硝酸塩及び塩化物からなる群より選択される少なくとも１種の化合物の水溶液である、本発明１６のイソシアネート化合物の製造方法に関する。
本発明１８は、前記金属化合物の水溶液が、リチウム化合物、カルシウム化合物及びマグネシウム化合物からなる群より選択される少なくとも１種の化合物の水溶液である、本発明１６又は１７のイソシアネート化合物の製造方法に関する。
本発明１９は、前記金属化合物の水溶液が、硝酸リチウム及び／又は硝酸カルシウムの水溶液である、本発明１６〜１８のいずれかのイソシアネート化合物の製造方法に関する。
本発明２０は、工程（Ｂ２）において多孔質シリカを用いる、本発明１３のイソシアネート化合物の製造方法に関する。
本発明２１は、前記多孔質シリカが、非晶質シリカである、本発明２０のイソシアネート化合物の製造方法に関する。
本発明２２は、前記多孔質シリカが、平均細孔径８ｎｍ〜３００μｍを有する、本発明２０又は２１のイソシアネート化合物の製造方法に関する。
本発明２３は、一般式（４）：

（式中、
Ｒ¹¹は、置換基を有していても良い炭化水素基を示し、
Ｒ¹²は、互いに独立して、置換基を有していても良い炭化水素基を示し、
ｐは、１〜４の整数を示す）で示されるカルバメート化合物を、多孔質シリカと、気相で接触させる工程を含む、一般式（５）：

（式中、Ｒ¹¹及びｐは、前記と同義である）で示されるイソシアネート化合物の製造方法に関する。
本発明２４は、前記多孔質シリカが、非晶質シリカである、本発明２３のイソシアネート化合物の製造方法に関する。
本発明２５は、前記多孔質シリカが、平均細孔径８ｎｍ〜５μｍを有する、本発明２３又は２４のイソシアネート化合物の製造方法に関する。
本発明２６は、アミン化合物とカーボネート化合物との反応生成物と、気相又は液相で接触させることによりイソシアネート化合物を与える、アルカリ金属化合物及びアルカリ土類金属化合物からなる群より選択される少なくとも１種の金属化合物が担体に担持されたイソシアネート製造用触媒に関する。
本発明２７は、アミン化合物とカーボネート化合物との反応生成物と、気相で接触させることによりイソシアネート化合物を与える、多孔質シリカからなるイソシアネート製造用触媒に関する。
本発明２８は、前記反応生成物が、カルバメート化合物を含む、本発明２６又は２７のイソシアネート製造用触媒に関する。
本発明２９は、アルカリ金属化合物及びアルカリ土類金属化合物からなる群より選択される少なくとも１種の水溶液に担体を含浸させ、次いで乾固及び／又は濾過し、得られた固体を焼成した焼成体である、イソシアネート製造用触媒に関する。
本発明３０は、多孔質シリカからなる、気相でのイソシアネート製造用触媒に関する。The present invention 1
(A) General formula (1) in the presence of an enzyme:

(Where
R ¹ represents a hydrocarbon group which may have a substituent,
n represents an integer of 1 to 4) and the general formula (2):

(Wherein R ² independently represents a hydrocarbon group which may have a substituent) and a step of reacting with a carbonate compound represented by (B) (B1) step (A) A step of contacting the reaction product in a liquid phase with a catalyst in which at least one metal compound selected from the group consisting of an alkali metal compound and an alkaline earth metal compound is supported on a carrier, or step (B2) ( The reaction product of A) is produced in the gas phase by a catalyst in which at least one metal compound selected from the group consisting of an alkali metal compound and an alkaline earth metal compound is supported on a support, and / or porous silica. General formula (3) including the process made to contact:

(Wherein R ¹ and n are as defined above)
It is related with the manufacturing method of the isocyanate compound shown by these.
The present invention 2 relates to the method for producing an isocyanate compound of the present invention 1, wherein the enzyme in the step (A) is an immobilized enzyme immobilized on a carrier.
The present invention 3 relates to the method for producing an isocyanate compound of the present invention 1, wherein the immobilized enzyme is inserted into a reaction vessel as a fixed bed.
This invention 4 relates to the manufacturing method of the isocyanate compound in any one of this invention 1-3 which performs reaction of a process (A) in presence of a solvent inert to reaction.
The present invention 5 relates to the method for producing an isocyanate compound of the present invention 4, wherein the solvent is at least one solvent selected from the group consisting of an aliphatic solvent, an aromatic solvent, and an ether solvent.
This invention 6 relates to the manufacturing method of the isocyanate compound in any one of this invention 1-5 in which the reaction product of a process (A) contains a carbamate compound.
This invention 7 relates to the manufacturing method of the isocyanate compound in any one of this invention 1-6 whose process (B) is a process (B1).
This invention 8 relates to the manufacturing method of the isocyanate compound of this invention 7 whose catalyst in a process (B1) is a sintered body.
The present invention 9 is obtained by impregnating a carrier with at least one aqueous solution selected from the group consisting of an alkali metal compound and an alkaline earth metal compound as the catalyst in the step (B1), and then drying and / or filtering. It is related with the manufacturing method of the isocyanate compound of this invention 8 which is the baked body which baked the obtained solid.
The present invention 10 relates to the method for producing an isocyanate compound of the present invention 9, wherein the aqueous solution of the metal compound is an aqueous solution of at least one compound selected from the group consisting of nitrates and chlorides.
This invention 11 relates to the manufacturing method of the isocyanate compound of this invention 9 or 10 whose aqueous solution of the said metal compound is an aqueous solution of the at least 1 sort (s) of compound selected from the group which consists of a lithium compound, a calcium compound, and a magnesium compound.
This invention 12 relates to the manufacturing method of the isocyanate compound in any one of this invention 9-11 whose aqueous solution of the said metal compound is aqueous solution of lithium nitrate and / or calcium nitrate.
This invention 13 relates to the manufacturing method of the isocyanate compound in any one of this invention 1-6 whose process (B) is a process (B2).
Invention 14 is an isocyanate compound of Invention 13 that uses a catalyst in which at least one metal compound selected from the group consisting of an alkali metal compound and an alkaline earth metal compound is supported on a carrier in the step (B2). This invention 15 relates to the manufacturing method of the isocyanate compound of this invention 14 whose said catalyst is a sintered body.
The present invention 16 is characterized in that the catalyst is impregnated with at least one aqueous solution selected from the group consisting of an alkali metal compound and an alkaline earth metal compound, and then dried and / or filtered. It is related with the manufacturing method of the isocyanate compound of this invention 15 which is a baked fired body.
The present invention 17 relates to the method for producing an isocyanate compound of the present invention 16, wherein the aqueous solution of the metal compound is an aqueous solution of at least one compound selected from the group consisting of nitrates and chlorides.
The present invention 18 relates to the method for producing an isocyanate compound of the present invention 16 or 17, wherein the aqueous solution of the metal compound is an aqueous solution of at least one compound selected from the group consisting of a lithium compound, a calcium compound and a magnesium compound.
This invention 19 relates to the manufacturing method of the isocyanate compound in any one of this invention 16-18 whose aqueous solution of the said metal compound is the aqueous solution of lithium nitrate and / or calcium nitrate.
This invention 20 relates to the manufacturing method of the isocyanate compound of this invention 13 which uses porous silica in a process (B2).
This invention 21 relates to the manufacturing method of the isocyanate compound of this invention 20 whose said porous silica is an amorphous silica.
The present invention 22 relates to the method for producing an isocyanate compound of the present invention 20 or 21, wherein the porous silica has an average pore diameter of 8 nm to 300 μm.
The invention 23 relates to the general formula (4):

(Where
R ¹¹ represents a hydrocarbon group which may have a substituent,
R ¹² independently of each other represents an optionally substituted hydrocarbon group;
p represents an integer of 1 to 4), and a step of bringing the carbamate compound into contact with porous silica in a gas phase is represented by the general formula (5):

(Wherein R ¹¹ and p are as defined above).
This invention 24 relates to the manufacturing method of the isocyanate compound of this invention 23 whose said porous silica is an amorphous silica.
This invention 25 relates to the manufacturing method of the isocyanate compound of this invention 23 or 24 with which the said porous silica has an average pore diameter of 8 nm-5 micrometers.
The present invention 26 provides at least one selected from the group consisting of an alkali metal compound and an alkaline earth metal compound that gives an isocyanate compound by contacting a reaction product of an amine compound and a carbonate compound in a gas phase or a liquid phase. The present invention relates to an isocyanate production catalyst in which a metal compound is supported on a carrier.
The present invention 27 relates to an isocyanate production catalyst comprising porous silica, which gives an isocyanate compound by contacting with a reaction product of an amine compound and a carbonate compound in a gas phase.
The present invention 28 relates to the isocyanate production catalyst of the present invention 26 or 27, wherein the reaction product contains a carbamate compound.
The present invention 29 is a fired body obtained by impregnating a carrier with at least one aqueous solution selected from the group consisting of an alkali metal compound and an alkaline earth metal compound, then drying and / or filtering, and firing the obtained solid It is related with the catalyst for isocyanate manufacture which is.
The present invention 30 relates to a catalyst for producing isocyanate in a gas phase, which is made of porous silica.

  According to the present invention, an isocyanate compound can be produced directly or continuously from an amine compound and a carbonate compound without isolating and purifying a carbamate compound produced as an intermediate.

It is the schematic of an example of the gaseous-phase fixed bed system used in the Example. It is the schematic of another example of the gaseous-phase fixed bed system used in the Example.

  In the present invention, an isocyanate compound and a carbonate compound are used as starting materials, and an isocyanate compound is produced directly or continuously without subjecting the carbamate compound produced as an intermediate to a special treatment (eg, isolation / purification). Is the method.

  The method of the present invention includes a step (A) and a step (B), the step (A) is a step of reacting an amine compound and a carbonate compound, and the step (B) is a reaction of the step (A). This is a process for producing an isocyanate compound from the product, and the process (B) is divided into a process (B1) and a process (B2) depending on the phase in which the reaction is performed. Hereinafter, each process will be described separately.

  The present invention relates to (A) general formula (1) in the presence of an enzyme:

(Where
R ¹ represents a hydrocarbon group which may have a substituent,
n represents an integer of 1 to 4)
An amine compound represented by the general formula (2):

(Wherein R ² independently represents a hydrocarbon group which may have a substituent) and a step of reacting with a carbonate compound represented by

The amine compound used in the step (A) of the present invention is represented by the general formula (1). In the general formula (1), R ¹ is a hydrocarbon group which may have a substituent.

In the general formula (1), n represents an integer from 1 to 4, n is one determined by the valency number corresponding R ^1, For example, R ¹ is a monovalent radical (e.g., cyclohexyl) In some cases, n is 1, and when R ¹ is a divalent group (eg, a cyclohexylene group), n is 2.

In the general formula (1), when n is 1, R ¹ is a monovalent hydrocarbon group which may have a substituent. Examples of such a hydrocarbon group include a methyl group, an ethyl group, and the like. An alkyl group having 1 to 18 carbon atoms such as a group, propyl group, butyl group, pentyl group, hexyl group, octyl group, 2-ethylhexyl group, nonyl group, decyl group, dodecyl group, octadecyl group, preferably hexyl group;
An alkenyl group having 2 to 6 carbon atoms such as a propenyl group, a butenyl group, a pentenyl group or a hexenyl group, preferably a propenyl group;
Cycloalkyl groups having 3 to 10 carbon atoms such as cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, methylcyclohexyl group, cyclooctyl group, dimethylcyclohexyl group, isophoryl group, norbornyl group, decalyl group, adamantyl group, etc. Is a cyclohexyl group;
Examples thereof include aryl groups having 6 to 14 carbon atoms such as phenyl group, tolyl group, xylyl group, naphthyl group, biphenylyl group, anthryl group and trimethylphenyl group, preferably tolyl group. These groups include various isomers.

In the general formula (1), when n is 2, R ¹ is a divalent hydrocarbon group which may have a substituent. Examples of such a hydrocarbon group include a methylene group and 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. A linear or branched alkylene group having 1 to 20 atoms, preferably a hexylene group;
Number of carbon atoms such as cyclopropylene group, cyclobutylene group, cyclopentylene group, cyclohexylene group, methylene-trimethylcyclohexyl group, bicyclohexylene group, bicyclo [2.2.1] heptane-2,6-diyl group 3 to 20 cycloalkylene groups, preferably cyclohexylene groups;
C1-C14 alkylene-cycloalkylene-alkylene such as 1,4-dimethylenecyclopentane group, 1,4-diethylenecyclopentane group, 1,4-dimethylenecyclohexane group, 1,4-diethylenecyclohexane group, etc. A group, preferably a 1,3-dimethylenecyclohexane group;
An arylene group having 6 to 20 carbon atoms such as a phenylene group, a tolylene group, a dimethylphenylene group, a naphthylene group, a biphenylene group, an anthrylene group or a trimethylphenylene group, preferably a tolylene group;
A cycloalkylene-alkylene-cycloalkylene group having 7 to 20 carbon atoms such as propylene bis (cyclohexylene), preferably a methylene biscyclohexylene group;
An alkylene-arylene-alkylene group having 8 to 24 carbon atoms such as a phenylenebis (methylene) group;
And an arylene-alkylene-arylene group having 13 to 30 carbon atoms such as a methylenebis (phenylene) group. The alkylene group may be an alkylidene group having 2 to 6 carbon atoms such as an ethylidene group, a propylidene group, a butylidene group, a pentylidene group, or a hexylidene group, and is preferably a propylidene group. These groups include various isomers.

In the general formula (1), when n is 3, R ¹ is a trivalent hydrocarbon group which may have a substituent. Examples of such a hydrocarbon group include methane, ethane, Linear or branched chain having 1 to 20 carbon atoms such as propane, butane, pentane, hexane, heptane, octane, nonane, decane, dodecane, 2-methylpropane, 2-methylhexane, tetramethylethane, etc. A trivalent residue derived from an alkane, preferably a trivalent residue derived from pentane;
Derived from cycloalkanes having 3 to 20 carbon atoms such as cyclopropane, cyclobutane, cyclopentane, cyclohexane, methylene-trimethylcyclohexane, bicyclohexane, methylenebiscyclohexane, bicyclo [2.2.1] heptane, etc. A trivalent residue, preferably derived from cyclohexane;
Trivalent residues derived from arenes having 6 to 20 carbon atoms such as benzene, toluene, xylene, naphthalene, biphenyl, anthracene, trimethylbenzene, etc., preferably trivalent residues derived from benzene. It is done. These groups include various isomers.

In the general formula (1), when n is 4, R ¹ is a trivalent hydrocarbon group which may have a substituent. Examples of such a hydrocarbon group include methane, ethane, Linear or branched chain having 1 to 20 carbon atoms such as propane, butane, pentane, hexane, heptane, octane, nonane, decane, dodecane, 2-methylpropane, 2-methylhexane, tetramethylethane, etc. A tetravalent residue derived from an alkane, preferably a trivalent residue derived from pentane;
Derived from cycloalkanes having 3 to 20 carbon atoms such as cyclopropane, cyclobutane, cyclopentane, cyclohexane, methylene-trimethylcyclohexane, bicyclohexane, methylenebiscyclohexane, bicyclo [2.2.1] heptane, etc. A tetravalent residue, preferably a trivalent residue derived from cyclohexane;
A tetravalent residue derived from an arene having 6 to 20 carbon atoms such as benzene, toluene, xylene, naphthalene, biphenyl, anthracene, trimethylbenzene, etc., preferably a trivalent residue derived from benzene . These groups include various isomers.

  In the general formula (1), examples of the substituent in the hydrocarbon which may have a substituent include a halogen atom (a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom), a cyano group, a carboxyl group, and an alkoxyl group. (For example, an alkoxy group having 1 to 4 carbon atoms, specifically a methoxy group, an ethoxy group, a propoxy group, a butoxy group, etc.), an aryloxy group (for example, an aryloxy group having 6 to 12 carbon atoms, specifically Phenoxy group and the like), alkylthio group (for example, alkylthio group having 1 to 6 carbon atoms, specifically methylthio group, ethylthio group, propylthio group, butylthio group and the like), arylthio group (for example, 6 to 6 carbon atoms). 12 phenylthio groups), (meth) acryloyloxy groups, and the like. As the substituent, a (meth) acryloyloxy group is preferable.

  Examples of the amine compound used in the step (A) of the present invention include monoamine compounds such as hexylamine, octylamine, dodecylamine, octadecylamine; 1,4-diaminobutane, 1,5-diaminopentane, 1,6 -Diaminohexane, 1,8-diaminooctane, 1,9-diaminononane, 1,10-diaminodecane, 1,12-diaminododecane, 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 (amino) Methyl) bicyclo [2,2,1] heptane, 1-amino-3,3,5-trimethyl-5- (aminomethyl)- Chlorohexane, 3-aminomethyl-3,5,5-trimethyl-1-aminocyclohexane, 2,2-bis (4-aminocyclohexyl) propane, 1,3- or 1,4-diaminomethylbenzene, 1,3 -Or 1,4-diaminobenzene, 2,4'- or 4,4'-diaminodiphenylmethane, 1,5- or 2,6-diaminonaphthalene, 4,4'-diaminobiphenyl, 2,4- or 2, Examples include diamine compounds such as 6-diaminotoluene and 2,2-bis (4-aminophenyl) propane; and triamine compounds such as 1,3,6-triaminohexane. In addition, the hydrocarbon part of these compounds contains various isomers.

  The amine compound is preferably 1,3-bis (aminomethyl) cyclohexane.

  The amine compounds may be used alone or in combination of two or more.

The carbonate compound used in the step (A) of the present invention is represented by the general formula (2). In the general formula (2), R ² is a hydrocarbon group which may have a substituent. Examples of such a hydrocarbon group include a methyl group, an ethyl group, a propyl group, and a butyl group. Examples thereof include a linear or branched alkyl group having 1 to 20 carbon atoms, preferably a linear or branched alkyl group having 1 to 6 carbon atoms, and more preferably a methyl group or an ethyl group. It is a group. These groups include various isomers.

  In the general formula (2), examples of the substituent in the hydrocarbon which may have a substituent include a halogen atom (a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom), an alkoxy group (for example, the number of carbon atoms) 1-4 alkoxy groups, specifically methoxy group, ethoxy group, propoxy group, butoxy group, etc.), cyano group, nitro group and the like.

  Examples of the carbonate compound used in the step (A) of the present invention include dimethyl carbonate, diethyl carbonate, dipropyl carbonate, dibutyl carbonate and the like, and dimethyl carbonate or diethyl carbonate is preferable. These carbonate compounds may be used alone or in combination of two or more.

  The amount of the carbonate compound used is preferably 1 to 100 mol with respect to 1 mol of the amine compound. By making the usage-amount of a carbonate compound into this range, the residual amount of an amine compound can be reduced, and by this, the carbamate compound (precursor of an isocyanate compound) and the amine compound which are produced | generated at the process (A) are reduced. The reaction can be suppressed. The amount of the carbonate compound used is more preferably 1 to 50 mol, more preferably 2 to 20 mol, particularly preferably 2 to 15 mol, and most preferably 2 to 10 mol, per 1 mol of the amine compound.

  The enzyme used in the step (A) of the present invention is preferably a hydrolase. Among them, preferred are protease, esterase and lipase, more preferred are porcine liver-derived esterase (PLE), porcine liver-derived lipase (PPL), lipase of microorganisms that can be isolated from yeast or bacteria, more preferably bulk. Lipases originating from Burkholderia cepacia (Pseudomonas cepacia) (for example, Amano PS (manufactured by Amano Enzyme), etc.), Candida antarctica (Candida antartica origin) (For example, Novozym 435 (manufactured by Novozyme) and the like), lipases originating from Rhizomucor Miehei (for example, Lipozyme) RM IM (manufactured by Novozyme), etc.), lipase originating from Thermomyces lanuginosus (Lipase TL), lipase originating from Mucor Miehei (Lipase MM), particularly preferably It is a lipase originating from Candida antarctica. These enzymes may be used alone or in combination of two or more. As these enzymes, commercially available products can be used as they are in natural form or as immobilized enzymes, but immobilized enzymes are preferably used in consideration of reactions in a fixed bed. These hydrolases were obtained from recombinant cultures obtained by introducing a gene encoding a hydrolase obtained from a microorganism as described above into an appropriate host such as yeast or filamentous fungus. It may be a thing.

  Recombinant DNA techniques used for recombinant expression of hydrolases are known in the art. The amino acid sequence of the hydrolase is not limited to the above. For example, in these sequences, one or several amino acids are deleted, substituted or added, and the hydrolase has a hydrolase activity. Proteins can be suitably used in the present invention. Alternatively, a protein consisting of an amino acid sequence exhibiting sequence identity with these sequences, for example, 90% or more, preferably 95% or more, more preferably 97% or more, and having hydrolase activity is also preferably used in the present invention. can do.

  The enzyme may be used in a natural form or commercially available as an immobilized enzyme after chemical treatment or physical treatment.

  As a chemical treatment or physical treatment method, for example, an enzyme is dissolved in a buffer solution (an organic solvent may be present if necessary), and this is directly or stirred and then freeze-dried. Is mentioned. As lyophilization, 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. The method of drying a substance is mentioned. By the treatment, catalytic activity (reactivity, selectivity, etc.) can be improved.

  As a form of use of the enzyme, an immobilized enzyme immobilized on a carrier is preferable, more preferably an immobilized enzyme, and further, an enzyme inserted as a fixed bed in a reaction vessel is preferable. By immobilizing the enzyme, it becomes easy to recover the enzyme after the reaction is completed, and by interpolating, not only the suspension bed but also the reaction form as a fixed bed can be selected, which is highly convenient.

  As the usage-amount of an enzyme, 0.1-1000 mg is preferable with respect to 1 g of amine compounds, More preferably, it is 1-200 mg, More preferably, it is 10-100 mg. The amount of enzyme used can also be indicated by liquid space velocity (LHSV = Liquid Hourly Space Velocity). In this case, the amount of enzyme used is preferably 0.01 to 50. By setting the amount of the enzyme used within this range, a sufficient reaction rate can be obtained in the reaction of step (A). The amount of enzyme used is more preferably 0.05 to 20, more preferably 0.1 to 10.

  The reaction in the step (A) of the present invention is carried out in the presence or absence of a solvent, but is preferably carried out in the presence of a solvent from the viewpoint of enzyme stability.

  The solvent is not limited as long as it is inert to the reaction, and can be preferably selected from those that do not deactivate the enzyme. Specifically, at least one selected from the group consisting of an aliphatic solvent, an aromatic solvent, and an ether solvent (particularly an acyclic ether solvent) is preferable.

  Aliphatic solvents include aliphatic hydrocarbon solvents and halogenated aliphatic hydrocarbon solvents, for example, 5 carbon atoms such as cyclopentane, cyclohexane, methylcyclohexane, ethylcyclohexane, isopropylcyclohexane, cycloheptane, and the like. -10 cycloalkanes; C5-C10 halogenated cycloalkanes such as chlorocyclopentane and chlorocyclohexane. From the viewpoint of solvent removal after the reaction, a cycloalkane having 5 to 10 carbon atoms is preferred, and cyclohexane and methylcyclohexane are more preferred. These solvents may be used alone or in combination of two or more.

  Aromatic solvents include aromatic hydrocarbon solvents and halogenated aromatic hydrocarbon solvents, for example, aromatic hydrocarbons such as benzene, toluene, xylene and mesitylene; halogens such as chlorobenzene and dichlorobenzene. Aromatic hydrocarbons. Aromatic hydrocarbons are preferable, and toluene and xylene are more preferable. These solvents may be used alone or in combination of two or more.

  The ether solvent is preferably an acyclic ether solvent, for example, 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. 5-18 cycloalkyl alkyl ethers; aralkyl alkyl ethers such as benzyl phenyl ether and benzyl methyl ether; diaralkyl ethers such as dibenzyl ether; 7 to 7 carbon atoms such as diphenyl ether and di (p-tolyl) ether 18 diaryl ethers. Preferred are dialkyl ethers and cyclohexyl alkyl ethers, more preferred are dialkyl ethers, and more preferred is diisopropyl ether. These solvents may be used alone or in combination of two or more.

  The solvent is preferably one or more selected from the group consisting of cycloalkanes having 5 to 10 carbon atoms, aromatic hydrocarbons and dialkyl ethers, and more preferably cyclohexane, methylcyclohexane, toluene, One or more selected from the group consisting of xylene and diisopropyl ether.

  When using a solvent at a process (A), Preferably the quantity of a solvent is 0.5-200 mL with respect to 1 g of amine compounds, More preferably, it is 1-50 mL, More preferably, it is 1-20 mL. When a plurality of types of solvents are used in combination, the mixing ratio can be appropriately selected and is not particularly limited.

  Step (A) can be performed, for example, by mixing an amine compound, a carbonate compound, an enzyme, and optionally a solvent, and reacting them with stirring. The reaction temperature at that time is preferably 20 ° C. to 90 ° C., more preferably 40 ° C. to 90 ° C., more preferably 40 ° C. to 70 ° C., and the reaction pressure is preferably normal pressure or reduced pressure. By carrying out the reaction of step (A) within this range, the reaction can proceed without inactivating the enzyme. You may carry out removing low boiling-point components, such as alcohol produced | generated in the middle of reaction.

  It is preferable that the manufacturing apparatus used for the step (A) has a form capable of performing the reaction in the step (A) and transferring the reaction product for the reaction in the step (B). It is desirable to have a form that can be transferred as it is after the completion of the step (A), and either a fixed bed or a fluidized bed can be selected according to the use mode of the enzyme. In particular, when an immobilized enzyme is used, it is desirable that the immobilized enzyme is inserted into the reaction vessel as a fixed bed. For example, the immobilized enzyme is formed on the inner wall of a tube made of an inert resin. Is preferably filled or deposited by physical or chemical techniques.

  After completion of the step (A), the reaction product can be subjected to the step (B) as it is or after a physical operation.

  The physical operation refers to an operation that does not cause a chemical reaction after the completion of the step (A), and includes, for example, an operation for transferring to the reactor in the step (B). For the transfer operation, for example, heating and cooling the reaction solution for the purpose of preventing inconvenience, operation for removing foreign matters by physical adsorption (filtering with a filter, activated carbon treatment, etc.) The operation of adjusting the entire volume by distilling off the solvent, adding a solvent inert to the reaction, or dividing the reaction solution may be mentioned. Its size, degree, etc. can be selected as appropriate.

  As the apparatus for transfer, for example, a connection part for transferring the reaction liquid is provided, and further a baffle plate and a filter for adjusting the flow rate, and a solid having a porous structure for promoting physical adsorption (for example, Examples of such devices include activated carbon. Its size, degree, etc. can be selected as appropriate.

  The reaction product of the step (A) includes a carbamate compound (compound corresponding to the raw material of the isocyanate compound) generated by the reaction between the amine compound and the carbonate compound. There is no problem even if the reaction product contains raw materials and by-products, but the amine compound as the raw material may react with the carbamate compound, so the amine compound should be consumed substantially. Is desirable.

The present invention relates to a catalyst in which at least one metal compound selected from the group consisting of an alkali metal compound and an alkaline earth metal compound is supported on a support as a reaction product of (B) (B1) step (A). The reaction product of the step of contacting in the liquid phase, or (B2) the reaction product of step (A), at least one metal compound selected from the group consisting of an alkali metal compound and an alkaline earth metal compound is supported on a carrier. By the step of contacting the catalyst and / or porous silica in the gas phase, the general formula (3):

(Where
R ¹ represents a hydrocarbon group which may have a substituent,
n represents an integer of 1 to 4)
The process of manufacturing the isocyanate compound shown by these is included.

About R < ¹ >, n in General formula (3), the description regarding the amine compound shown by General formula (1) and a preferable illustration are applied.

  In the step (B1), the reaction product of the step (A) is obtained in a liquid phase with a catalyst in which at least one metal compound selected from the group consisting of an alkali metal compound and an alkaline earth metal compound is supported on a carrier. It is a process of making it contact. Hereinafter, “at least one metal compound selected from the group consisting of alkali metal compounds and alkaline earth metal compounds” may be collectively referred to as “metal compound”, and “alkali metal in step (B1)” may be referred to. The “catalyst in which at least one metal compound selected from the group consisting of a compound and an alkaline earth metal compound is supported on a carrier” may be referred to as “catalyst of step (B1)”.

  Examples of the alkali metal compound include inorganic salts of alkali metals such as nitrates, carbonates, hydrogen carbonates, and silicates; halides of alkali metals such as fluorides and chlorides; hydroxides of alkali metals; alkalis Metal oxides: Alkali metal organic acid salts such as acetates and oxalates are used. The alkali metal compound may be a hydrate. The same applies to the following. The alkali metal compounds may be used alone or in combination of two or more.

  Examples of the alkali metal of the alkali metal compound include lithium, sodium, potassium, rubidium, and cesium, preferably lithium, sodium, potassium, and more preferably lithium. The alkali metal contained in the alkali metal compound may be used alone or in combination of two or more.

  Examples of the alkaline earth metal compound include inorganic earth salts of alkaline earth metals such as nitrates, carbonates, hydrogen carbonates and silicates; halides of alkaline earth metals such as fluorides and chlorides; alkaline earths Alkali earth metal oxides; alkaline earth metal oxides; organic acid salts of alkaline earth metals such as acetates and oxalates are used. The alkaline earth metal compound may be a hydrate. The same applies to the following. The alkaline earth metal compounds may be used alone or in combination of two or more.

  Examples of the alkaline earth metal of the alkaline earth metal compound include beryllium, magnesium, calcium, strontium, barium and the like, preferably magnesium, calcium, strontium, barium, and more preferably calcium. The alkaline earth metal contained in the alkaline earth metal compound may be used alone or in combination of two or more.

  Although the particle diameter of a support | carrier is not specifically limited, Usually, it is 0.5 mm-10 mm. As the carrier, one having an average pore diameter of 8 nm to 300 μm can be used. Here, the average pore diameter is a value measured by a physical adsorption method (nitrogen adsorption method) when 50 nm or less, and a value exceeding 50 nm is a value measured by a mercury intrusion method. The catalyst in the step (B1) preferably has an average pore diameter of 8 nm to 50 μm, more preferably an average pore diameter of 8 nm to 5 μm, and more preferably an average pore diameter of 8 nm to 1 μm. .

  Examples of the carrier include activated carbon; metal oxides such as silica, alumina, silica alumina, zirconia, and titania; complex metal oxides such as titania silica, titania zirconia, zirconia silica, and hydrotalcite; kaolin, smectite, bentonite, Examples thereof include clay minerals such as chlorite and illite; metallosilicates such as zeolite; metal oxide precursors such as silica sol and alumina sol. Preferred are metal oxides and composite metal oxides, more preferred are silica, alumina, silica alumina, more preferred is silica, and most preferred is porous silica having an average pore diameter of 8 nm to 1 μm.

  The catalyst in the step (B1) may be a catalyst in which different types of metal compounds are supported on the same carrier, or a catalyst in which metal compounds are supported on separate carriers and then physically mixed.

  The amount of the metal compound supported on the carrier in the catalyst in the step (B1) is preferably 0.01 to 50% by mass, more preferably 0.05 to 30% by mass, and more preferably 0.1 to 30% by mass in terms of metal. These values are 20% by mass, and these numerical values can be measured using an ICP-AES method (inductively coupled plasma method) or the like.

  The catalyst of the step (B1) can be prepared from a support and a metal compound (at least one metal compound selected from the group consisting of alkali metal compounds and alkaline earth metal compounds). The catalyst in the step (B1) is preferably a fired body, more preferably a fired body fired at 300 to 1000 ° C., more preferably a fired body fired at 400 to 800 ° C., and particularly preferably 450. It is a fired body fired at ˜600 ° C. Such a fired body can be obtained, for example, by impregnating a carrier with an aqueous solution of a metal compound, then drying and / or filtering, and firing the resulting solid. The aqueous solution of the metal compound (preferably lithium compound or calcium compound) is preferably an aqueous solution of at least one compound selected from the group consisting of nitrates and chlorides, for example, an aqueous solution of lithium nitrate and / or calcium nitrate. It is done.

  As a method for impregnating a carrier with an aqueous solution of a metal compound, a general impregnation method can be adopted, and a pore filling method, an evaporation to dryness method, an equilibrium adsorption method, and an incipient wetness method are preferable.

  After impregnation, it can be obtained by drying and / or filtering, and firing the obtained solid. As a method for drying and filtering, a general method can be employed. The resulting solid can be dried before firing. The drying temperature at that time is preferably 50 to 150 ° C., more preferably 80 to 120 ° C., and the drying time is not particularly limited as long as water can be substantially removed, but preferably 6 to 36 hours. More preferably, it is 12 to 24 hours.

  The obtained solid can be calcined after being optionally dried. Firing conditions can be adjusted as appropriate depending on the type and form of the metal compound and carrier, the amount supported, and the dry state. The firing temperature is preferably 300 ° C to 1000 ° C. By calcining in this range, it is possible to obtain the catalytic activity (improved catalytic activity, improved selectivity, etc.) required in the step (B1) of the present invention. The firing temperature is more preferably 400 to 800 ° C, and more preferably 450 to 600 ° C. The firing time is not particularly limited as long as the firing is sufficiently performed, but is preferably 1 to 10 hours, and more preferably 2 to 5 hours.

  Specifically, an alkali metal (preferably lithium) nitrate and / or an alkaline earth metal (preferably calcium) nitrate solution is impregnated with silica (preferably porous silica having an average pore diameter of 8 nm to 1 μm). The solid obtained by drying and / or filtering is preferably calcined in air (in the presence of oxygen) at 300 to 1000 ° C., more preferably at 400 to 800 ° C., more preferably at 500 to 600 ° C. Can be obtained.

  The amount of the catalyst used in the step (B1) depends on the amount of carbamate compound contained in the reaction product of the step (A), but is preferably 0 with respect to 1 mol of the amine compound used in the step (A). 0.1 to 100% by mass, and more preferably 0.5 to 50% by mass. In this case, it is preferable that the amine compound is substantially completely consumed in the step (A).

  The reaction product of step (A) to be applied to step (B1) may be one whose total volume is adjusted by using an inert solvent. “Inert” in an inert solvent affects the carbamate compound present as the main component at the end of step (A), the isocyanate compound that is the reaction product of step (B1), and the catalyst used. Means that

  Examples of the inert solvent include esters such as dioctyl phthalate, didecyl phthalate and didodecyl phthalate; dibenzyltoluene, triphenylmethane, phenylnaphthalene, biphenyl, terphenyl, diethylbiphenyl, triethylbiphenyl, 1,3 And aromatic hydrocarbons such as 5-triisopropylbenzene. These solvents may be used alone or in combination of two or more. The amount used can be appropriately adjusted depending on the reaction apparatus and reaction form.

  In the step (B1), for example, the reaction product obtained in the step (A), the catalyst of the step (B1) (at least one metal compound selected from the group consisting of an alkali metal compound and an alkaline earth metal compound is included. (Catalyst supported on a carrier), and optionally an inert solvent, may be mixed and brought into contact with stirring. The reaction temperature at that time is preferably 80 ° C. to 350 ° C., more preferably 100 ° C. to 300 ° C., more preferably 150 ° C. to 220 ° C., and the reaction pressure is preferably normal pressure or reduced pressure. By carrying out the reaction of the step (B1) within this range, a high reaction rate can be obtained in the step (B1), and the generation of by-products in the reaction of the step (B1) is suppressed, and the purpose is high. Can be obtained. Examples of the inert solvent that can be used in the step (B1) include the solvents exemplified for adjusting the total volume of the reaction product in the step (A).

  Step (B1) is performed while removing low-boiling components (such as alcohol) that are by-produced during the reaction and compounds remaining as a part of the raw material (for example, unreacted carbonate compound and the like in step (A)). May be. Moreover, as long as the boiling point of the isocyanate compound which is a target object seems to be low, you may carry out, taking out the isocyanate compound to produce | generate.

  Thus, when performing while removing or taking out components from the reaction system of the step (B1), it is desirable that the reactor is equipped with a device for such operation (for example, a distillation device, a trap, etc.). . Further, it is desirable to remove and take out under reduced pressure. The pressure at that time is preferably 0.1 to 90 kPa, more preferably 0.5 to 30 kPa.

  In the step (B2), the reaction product of the step (A) is a catalyst in which at least one metal compound selected from the group consisting of an alkali metal compound and an alkaline earth metal compound is supported on a support, and / or porous. This is a step of contacting the porous silica with the porous silica in the gas phase.

  In step (B2), after completion of step (A), the product obtained by vaporizing the reaction product by heating and / or decompressing is subjected to the reaction. Prior to vaporization, a physical operation (such as an operation for transfer) can be performed in some cases.

  The heating and / or decompression conditions for vaporization can be selected as appropriate. Since the reaction product of the step (A) contains a carbamate compound as a main component, the temperature at which the carbamate compound can be vaporized can be selected, for example, 250 to 500 ° C., preferably 300 to 450 ° C. it can. Moreover, although a pressure can be fluctuate | varied from the relationship with heating temperature, from the point of workability | operativity, it can be 0.1-90 kPa, for example, Preferably it can be 0.1-30 kPa.

  In the step (B2), a catalyst in which at least one metal compound selected from the group consisting of an alkali metal compound and an alkaline earth metal compound is supported on a support, porous silica, or a combination thereof is used.

  A catalyst in which at least one metal compound selected from the group consisting of an alkali metal compound and an alkaline earth metal compound in the step (B2) is supported on a carrier (hereinafter referred to as a catalyst in the step (B2)) is a step (B1 The description and preferred examples of the catalyst in (1) apply. However, as the catalyst carrier in the step (B2), those having an average pore diameter of 8 nm to 300 μm can be used as in the catalyst of the step (B1), but those having an average pore diameter of 30 nm to 50 μm can be used. More preferably, the average pore diameter is 30 nm to 5 μm, and more preferably the average pore diameter is 30 nm to 1 μm.

  The porous silica in the step (B2) itself functions as a catalyst. As the porous silica, those having an average pore diameter of 8 nm to 300 μm can be used as in the catalyst of the step (B1), but the porous silica is not limited thereto. From the viewpoint of reaction activity and selectivity, the average pore diameter is preferably 8 nm to 5 μm, more preferably 10 nm to 5 μm, further preferably 10 nm to 1 μm, and particularly preferably 30 nm to 1 μm. Here, the average pore diameter is a value measured by a physical adsorption method (nitrogen adsorption method) when 50 nm or less, and a value exceeding 50 nm is a value measured by a mercury intrusion method.

In terms of reaction activity and selectivity, the porous silica preferably has a pore volume of 0.1 to 2 mL / g, more preferably 0.3 to 1.5 mL / g, and still more preferably 0. .5 to 1 mL / g. Moreover, it is preferable that a specific surface area is 1-800 m < ² > / g, More preferably, it is 5-300 m < ² > / g, More preferably, it is 10-100 m < ² > / g.

  Examples of the porous silica include amorphous silica, and any of synthetic amorphous silica produced by a dry method or a wet method can be used. In addition, as for amorphous silica, for example, a commercially available product containing moisture can be used for the reaction as it is. Silica gel can also be suitably used.

  Examples of the porous silica include Caret Q10, Caret Q50, Caret Q100, Caret Q300, and the like manufactured by Fuji Silysia Chemical Ltd.

  Porous silica can also be used after sieving so as to be applicable to the apparatus.

  In the step (B2) of the present invention, the reaction product transferred from the step (A) is brought into contact with the catalyst and / or porous silica in the step (B2) in the gas phase, whereby the target isocyanate compound is obtained. It is a manufacturing process. Thereby, an isocyanate compound can be directly or continuously produced from an amine compound and a carbonate compound without isolating and purifying a carbamate compound produced as an intermediate. However, from the viewpoint of the form and capacity of the apparatus, a necessary apparatus can be provided or a necessary operation can be performed to the extent that direct or continuous reaction is not impaired.

  In the step (B2) of the present invention, a method used for a solid catalyst reaction in a gas phase such as a fixed bed method, a moving bed method, and a fluidized bed method can be adopted, and among them, a gas phase fixed bed method is preferable.

  The gas phase fixed bed system includes, for example, a raw material tank (1), a substrate supply pump (2), a tubular reactor (3) filled with a catalyst, a heat source (such as a tubular electric furnace) for heating the reactor (4), production Physical heat exchanger (6), receiver (7) for collecting condensed product isocyanate compound, heat exchanger (8) for alcohol condensation, receiver (9) for alcohol acquisition, vacuum pump ( Although it can be constituted by a vacuum line connected to 17), it is not limited to this.

  In the step (B2), the catalyst of the step (B2) is preferably used in an amount of 0.01 to 10 g, more preferably 0.02 to 5 g with respect to the reaction product supply rate of 1 g / h in the step (A). The porous silica is preferably used at 0.05 to 20 g, more preferably 0.2 to 9 g.

  In the step (B2), the supply rate of the reaction product in the step (A) is preferably 0.1 to 100 g / h, more preferably 0.2 to 50 g / h, with respect to 1 g of the catalyst. More preferably, it is 0.2-10 g / h.

  The reaction in the step (B2) may be performed with an inert gas such as nitrogen or without using an inert gas as long as the reaction product of the step (A) is vaporized. It may be performed under normal pressure or reduced pressure.

  The isocyanate compound obtained by the step (A) and the step (B) of the present invention is, for example, filtered, concentrated, extracted, distilled from the reaction solution after the step (B) (the step (B1) or the step (B2)). It can be isolated and purified by general operations such as sublimation, recrystallization and column chromatography. The obtained isocyanate compound can be made into a high-purity isocyanate compound by further refining.

  Catalyst for use in a catalyst in which at least one metal compound selected from the group consisting of alkali metal compounds and alkaline earth metal compounds used in steps (B1) and (B2) of the present invention is supported on a carrier, and step The porous silica used in (B2) is an isocyanate compound without impairing the activity even when a reaction product (mainly composed of a carbamate compound) obtained by reacting an amine compound with a carbonate compound is brought into direct contact. It is also a novel catalyst for isocyanate production that can be derived into

（式中、
Ｒ¹¹は、置換基を有していても良い炭化水素基を示し、
Ｒ¹²は、互いに独立して、置換基を有していても良い炭化水素基を示し、
ｐは、１〜４の整数を示す）で示されるカルバメート化合物を、多孔質シリカと、気相で接触させる工程を含む、一般式（５）：

（式中、Ｒ¹¹及びｐは、前記と同義である）で示されるイソシアネート化合物の製造方法に関する。Furthermore, the present invention relates to a general formula (4):

(Where
R ¹¹ represents a hydrocarbon group which may have a substituent,
R ¹² independently of each other represents an optionally substituted hydrocarbon group;
p represents an integer of 1 to 4), and a step of bringing the carbamate compound into contact with porous silica in a gas phase is represented by the general formula (5):

(Wherein R ¹¹ and p are as defined above).

In the general formula (4), the description and preferred examples relating to R ¹ in the general formula (1) are applied to R ¹¹ . In application, n shall be read as p.

In the general formula (4), the description and preferred examples relating to R ² in the general formula (2) are applied to R ¹² .

  Examples of the carbamate compound of the general formula (4) include methyl hexyl carbamate, methyl octyl carbamate, methyl dodecyl carbamate, methyl 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 (butoxycarbonylamino) octane, 1,8-bis (phenoxycarbonylamino) -4- (Feno Cicarbonylaminomethyl) 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 (methoxycarbonylamino) hexane, 1,3 Aliphatic carbamate compounds such as 1,6-tris (phenoxycarbonylamino) hexane, preferably methyl hexyl carbamate, methyl octyl carbamate, methyl dodecyl carbamate, 1,4-bis (methoxycarbonylamino) butane, 1,5 -Bis (Metoki Carbonylamino) pentane, 1,6-bis (methoxycarbonylamino) hexane, 1,8-bis (methoxycarbonylamino) octane, 1,9-bis (methoxycarbonylamino) nonane, 1,10-bis (methoxycarbonylamino) ) -Decane, 1,12-bis (methoxycarbonylamino) -dodecane and the like.

  Examples of the alicyclic carbamate compound include 1,3- or 1,4-bis (methoxycarbonylamino) cyclohexane, 1,3- or 1,4-bis (ethoxycarbonylamino) cyclohexane, 1,3. -Or 1,4-bis (butoxycarbonylamino) cyclohexane, 1,3- or 1,4-bis (methoxycarbonylaminomethyl) cyclohexane, 1,3- or 1,4-bis (ethoxycarbonylaminomethyl) cyclohexane, 1,3- or 1,4-bis (butoxycarbonylaminomethyl) cyclohexane, 2,4′- or 4,4′-bis (methoxycarbonylamino) dicyclohexylmethane, 2,4′- or 4,4′-bis (Ethoxycarbonylamino) dicyclohexylmethane, 2,4′- or 4,4′-bis ( Toxicarbonylamino) dicyclohexylmethane, 2,4′- or 4,4′-bis (phenoxycarbonylamino) 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- (butoxycarbonylaminomethyl) -cyclohex 3- (methoxycarbonylaminomethyl) -3,5,5-trimethyl-1- (methoxycarbonylamino) cyclohexane, 4,4′-bis (methoxycarbonylamino) -2,2′-dicyclohexylpropane, 4, Examples thereof include 4′-bis (butoxycarbonylamino) -2,2′-dicyclohexylpropane, and preferably 1,3- or 1,4-bis (methoxycarbonylamino) cyclohexane, 1,3- or 1,4- Bis (methoxycarbonylaminomethyl) cyclohexane, 1- (methoxycarbonylamino) -3,3,5-trimethyl-5- (methoxycarbonylaminomethyl) -cyclohexane, 3- (methoxycarbonylaminomethyl) -3,5,5 -Trimethyl-1- (methoxycarbonylamino) cyclohexane, etc. It is.

  Furthermore, examples of the aromatic carbamate compound include 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, 2,2′-bis (4-propoxycarbonylaminophenyl) propane, 2,4′- or 4,4′-bis (methoxycarbonylamino) diphenylmethane, 2,4′-bis (ethoxycarbonylamino) diphenylmethane, 2, 4′-bis (butoxycarbonylamino) diphenylmethane, 4,4′-bis (phenoxy) Rubonylamino) diphenylmethane, 1,5- or 2,6-bis (methoxycarbonylamino) 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, etc., preferably 1,3- or 1,4-bis (methoxycarbonylaminomethyl) benzene, 1,3- or 1,4-bis. (Methoxycarbonylamino) benzene, 1,3- or 1,4-bis (butoxycarbonylamino) ben Emissions, a 2,4- or 2,6-bis (methoxycarbonylamino) toluene.

R ¹¹ and p in the general formula (5) are as defined above, and the corresponding isocyanate compound is obtained using the carbamate compounds exemplified above.

  About porous silica, the description of porous silica used at a process (B2) and a preferable illustration are applied.

  As for the conditions in the gas phase reaction (evaporation method of carbamate compound, reaction method, supply rate, etc.), the description and preferred examples relating to the conditions in the case of using porous silica in the step (B2) are applied.

  According to the present invention, an isocyanate compound can be obtained from a carbamate compound by a simple method without using an expensive metal component. Further, after the reaction, the silica can be recovered, and the recovered silica can be used as it is or at a temperature at which solvent is washed or the attached organic matter is removed, for example, 300 ° C. to 700 ° C., preferably 400 to 600 ° C. It can be reused after being reactivated by a known method such as heat treatment, which is highly convenient.

  Next, the present invention will be specifically described with reference to examples, but the scope of the present invention is not limited thereto.

Production Example 1 (Production of silica-supported calcium catalyst (Ca / SiO ₂ ))
1.6 g (6.7 mmol) of calcium nitrate tetrahydrate and 13.0 g of ion-exchanged water were added to a flask with an internal volume of 50 mL and mixed with stirring to obtain an aqueous calcium nitrate solution. Next, 4.0 g (66.6 mmol) of silica powder (Fuji Silysia Chemical's Caract Q10, particle size 20 to 150 μm, average pore size 10 nm) was added and stirred at room temperature for 1 hour. After water was evaporated to dryness from the obtained suspension, the dried product was dried at 110 ° C. for 12 hours, and then calcined in air at 500 ° C. for 2 hours to obtain a silica-supported calcium catalyst (Ca / 4.3 g of SiO ₂ ) was obtained.
When the obtained catalyst (Ca / SiO ₂ ) was analyzed by ICP-AES, the calcium loading ratio relative to the total catalyst mass was 6.2% by mass.

Production Example 2 (Production of silica-supported lithium catalyst (Li / SiO ₂ ))
To a flask with an internal volume of 50 mL, 0.46 g (6.7 mmol) of lithium nitrate and 13.0 g of ion exchange water were added and mixed with stirring to obtain an aqueous lithium nitrate solution. Next, 4.0 g (66.6 mmol) of silica powder (Fuji Silysia Chemical's Caract Q10, particle size 20 to 150 μm, average pore size 10 nm) was added and stirred at room temperature for 1 hour. After water was evaporated to dryness from the resulting suspension, the dried product was dried at 110 ° C. for 12 hours, and then calcined in air at 500 ° C. for 2 hours to obtain a silica-supported lithium catalyst (Li / 4.0 g of SiO ₂ ) was obtained.
When the obtained catalyst (Li / SiO ₂ ) was analyzed by ICP-AES, the lithium supporting ratio relative to the total catalyst mass was 1.2% by mass.

Production Example 3 (Production of silica-supported calcium catalyst (Ca / SiO ₂ ))
240.0 g of water and 19.2 g of polyethylene glycol (manufactured by Wako Pure Chemical Industries, Ltd., average molecular weight 20,000) were mixed and stirred in a polyethylene container to obtain a uniform solution. To this, 240 mL of tetraethyl orthosilicate and 23.2 g of a 60% nitric acid aqueous solution (manufactured by Wako Pure Chemical Industries, Ltd.) were added, sealed and vigorously stirred for 1 hour. The gel was further allowed to stand at 50 ° C. for 12 hours, and the produced gel was taken out, washed with purified water, dried at 110 ° C. for 12 hours, and baked in air at 600 ° C. for 2 hours to obtain 7.6 g of silica gel. The average pore diameter of the silica gel was 1.6 μm as measured by a mercury intrusion method (measuring device: fully automated pore distribution measuring device, Por Master 60-GT manufactured by Quanta Chrome Co.). This was pulverized in a mortar and sieved to a particle size range of 1 mm to 2 mm. Calcium nitrate tetrahydrate (17.7 g, 74.9 mmol) and ion-exchanged water (18.8 g) were mixed and stirred in a flask to obtain an aqueous calcium nitrate solution. After adding 15.0 g (249.7 mmol) of the prepared silica gel to this aqueous calcium nitrate solution, it was dried at 110 ° C. for 12 hours, and calcined in air at 500 ° C. for 2 hours to obtain a catalyst (Ca / SiO ₂ ). 7 g was obtained. In the obtained catalyst (Ca / SiO ₂ ), 17.0% by mass of the calcium compound was supported on the catalyst in terms of calcium.

Synthesis of isocyanate compound by combination of step (A) and step (B1)

Example 1 (Synthesis of n-hexyl isocyanate)
(Process (A))
From a glass container having an internal volume of 200 mL equipped with a stirrer, a thermometer and a cooling device, derived from 10 g (99 mmol) of n-hexylamine, 54 g (605 mmol) of dimethyl carbonate, 100 mL of toluene and Candida antarctica Lipase 0.5g (Novozym 435 (trade name); manufactured by Novozyme) was added and reacted at 70 ° C for 22 hours with stirring. After completion of the reaction, the obtained reaction solution (hereinafter referred to as “reaction solution 1”) was passed through a filter and transferred to a dropping funnel provided in the reaction vessel used in step (B1).

(Process (B1))
Obtained in Production Example 1 into a glass container with an internal volume of 100 mL equipped with a dropping funnel (containing reaction liquid 1), Vigreux fractionation pipe (Claisen type), cooling pipe, flask and trap (cooled with cold ethanol). Catalyst (Ca / SiO ₂ ) 0.8 g (1.2 mmol as calcium), NeoSK-OIL1400 (manufactured by Soken Technics Co., Ltd., main component: dibenzyltoluene), 180 ° C. / While reacting at 6 kPa, the distillate containing the produced n-hexyl isocyanate was obtained by liquefying through a condenser. It took 4 hours for the distillation to stop.
When the obtained distillate was analyzed by gas chromatography, 22.7 mmol of n-hexyl isocyanate was contained in the distillate (reaction yield based on n-hexylamine; 36%).

Example 2 (Synthesis of n-hexyl isocyanate)
In Example 1, except that the catalyst was changed to the catalyst obtained in Production Example 2, when the reaction was carried out in the same manner as in Example 1, n-hexyl isocyanate was produced to the same extent as in Example 1.

Example 3 (Synthesis of n-hexyl isocyanate)
(Process (A))
From a glass container having an internal volume of 200 mL equipped with a stirrer, a thermometer and a cooling device, derived from 10 g (99 mmol) of n-hexylamine, 54 g (605 mmol) of dimethyl carbonate, 100 mL of toluene and Candida antarctica Lipase 0.5g (Novozym 435 (trade name); manufactured by Novozyme) was added and reacted at 70 ° C for 24 hours with stirring. After completion of the reaction, the obtained reaction solution (hereinafter referred to as “reaction solution 2”) is passed through a filter, and then the solvent in step (A) is mainly distilled off under reduced pressure (0.13 kPa) to obtain a total volume. Was reduced (10% of the original volume). This solution is referred to as “the concentrate of the reaction solution 2”.
(Process (B1))
0.8 g of catalyst (Ca / SiO ₂ ) obtained in Production Example 1 (1.2 mmol as calcium) was placed in a 100 mL glass container equipped with a Vigreux fractionation tube (Claisen type), a cooling tube, a flask and a trap. ), NeoSK-OIL1400 (manufactured by Soken Technics Co., Ltd., main component: dibenzyltoluene), charged with the concentrated solution of the reaction solution 2 obtained in the step (A), and 180 ° C / While reacting at 6 kPa, the distillate containing the produced n-hexyl isocyanate was obtained by liquefying through a condenser. It took 3 hours for the distillation to stop.
When the obtained distillate was analyzed by gas chromatography, 21.5 mmol of n-hexyl isocyanate was contained in the distillate (reaction yield based on n-hexylamine; 34%).

Comparative Example 1 (Synthesis of n-hexyl isocyanate)
In Example 3, except that the catalyst was changed to calcium oxide (CaO), when the reaction was carried out in the same manner as in Example 3, much methyl (n-hexyl) carbamate, which is a precursor of n-hexyl isocyanate, was recovered. The target n-hexyl isocyanate has a low yield of about 20%.

Comparative Example 2 (Synthesis of n-hexyl isocyanate)
(Process (A))
N-Hexylamine 19 g (186 mmol), dimethyl carbonate 72 g (800 mmol) and sodium methoxide (28% methanol solution) 1.1 mL were added to a 200 mL glass container equipped with a stirrer, thermometer and cooling device. The mixture was reacted at 50 ° C. for 2.5 hours with stirring. After completion of the reaction, the resulting reaction liquid (hereinafter referred to as “reaction liquid 22”) was mainly distilled off the solvent in step (A) under reduced pressure (0.13 kPa) to reduce the total volume (initially 36% of volume). This solution is referred to as “the concentrated liquid of the reaction liquid 22”.
(Process (B1))
0.4 g of catalyst (Ca / SiO ₂ ) obtained in Production Example 3 (1.2 mmol as calcium) in a 100 mL glass container equipped with a Vigreux fractionation tube (Claisen type), a cooling tube, a flask and a trap ), 30 g of NeoSK-OIL1400 (manufactured by Soken Technics Co., Ltd., main component: dibenzyltoluene), charged with the concentrated liquid of the reaction liquid 22 obtained in the step (A), and 180 ° C. / While reacting at 6 kPa, the distillate containing the produced n-hexyl isocyanate was obtained by liquefying through a condenser. It took 3 hours for the distillation to stop.
When the obtained distillate and the contents of the flask were analyzed by gas chromatography, the conversion rate was 100%, and as a product, n-hexyl isocyanate was 13% yield (selectivity 13%) with respect to hexylamine. Thus, methyl n-hexylcarbamate was obtained in a yield of 16%.
Comparative Example 3 (Synthesis of n-hexyl isocyanate)
(Process (A))
In a glass container having an internal volume of 200 mL equipped with a stirrer, a thermometer and a cooling device, 20 g (99 mmol) of n-hexylamine, 53 g (588 mmol) of dimethyl carbonate and 10 g of lipase derived from Candida antarctica ( Novozym 435 (trade name); manufactured by Novozyme) was added and reacted at 70 ° C. for 8 hours with stirring. After completion of the reaction, the obtained reaction solution (hereinafter referred to as “reaction solution 25”) is passed through a filter, and then the solvent in step (A) is mainly distilled off under reduced pressure (0.13 kPa) to obtain a total volume. (44% of the original volume). This solution is referred to as “the concentrated solution of the reaction solution 25”.
(Process (B1))
Into a 100 mL glass container equipped with a Vigreux fractionation tube (Claisen type), a cooling tube, a flask and a trap, a carrier ct Q300 (average pore size 300 nm, particle size 1.1 to 2 manufactured by Fuji Silysia Chemical Ltd.) as a catalyst. .2 mm) 0.4 g, NeoSK-OIL1400 (manufactured by Soken Technics Co., Ltd., main component: dibenzyltoluene) 30 g, charged with the concentrated solution of reaction solution 25 obtained in step (A), and by-produced methanol was removed. The distillate containing n-hexyl isocyanate produced while performing the reaction at 180 ° C. (6 kPa) was liquefied through a condenser. It took 2 hours for the distillation to stop.
When the obtained distillate and the contents of the flask were analyzed by gas chromatography, the conversion rate was 100%, and as a product, n-hexyl isocyanate was 9% yield (selectivity 9%) with respect to hexylamine. N-hexyl carbamate as a product was obtained in a yield of 92%.

Comparative Example 4 (Synthesis of n-hexyl isocyanate)
(Process (A))
From a glass container having an internal volume of 200 mL equipped with a stirrer, a thermometer and a cooling device, 10 g (99 mmol) of n-hexylamine, 27 g (296 mmol) of dimethyl carbonate, 63 mL of toluene and Candida antarctica (Candida antarctica) 5 g of lipase (Novozym 435 (trade name); manufactured by Novozyme) was added and reacted at 70 ° C. for 8 hours with stirring. After completion of the reaction, the obtained reaction solution (hereinafter referred to as “reaction solution 26”) is passed through a filter, and then the solvent in step (A) is mainly distilled off under reduced pressure (0.13 kPa) to obtain a total volume. Was reduced (17% of the original volume). This solution is referred to as “the concentrate of the reaction solution 26”.
(Process (B1))
Into a 100 mL glass container equipped with a Vigreux fractionation tube (Claisen type), a cooling tube, a flask and a trap, a carrier ct Q300 (average pore size 300 nm, particle size 1.1 to 2 manufactured by Fuji Silysia Chemical Ltd.) as a catalyst. .2 mm) 0.4 g, NeoSK-OIL1400 (manufactured by Soken Technics Co., Ltd., main component: dibenzyltoluene) 30 g, charged with the concentrated solution of reaction solution 26 obtained in step (A) to remove by-product methanol The distillate containing n-hexyl isocyanate produced while performing the reaction at 180 ° C. (6 kPa) was liquefied through a condenser. It took 2 hours for the distillation to stop.
When the obtained distillate and the contents of the flask were analyzed by gas chromatography, the conversion rate was 100%, and as a product, n-hexyl isocyanate was 11% yield (selectivity 11%) with respect to hexylamine. N-hexyl carbamate as a product was obtained in a yield of 87%.

Synthesis of isocyanate compound by combination of step (A) and step (B2)

Example 4 (Synthesis of 1,3-bis (isocyanatomethyl) cyclohexane)
(Process (A))
In a glass container having an internal volume of 1 L equipped with a stirrer, a thermometer and a cooling device, 30 g (0.21 mol) of 1,3-bis (aminomethyl) cyclohexane, 116 g (1.3 mol) of dimethyl carbonate, 300 mL of toluene and Candida -3 g of lipase derived from Candida antarctica (Novozym 435 (trade name); manufactured by Novozyme) was added and reacted at 70 ° C. for 42 hours with stirring. After completion of the reaction, the obtained reaction solution (hereinafter referred to as “reaction solution 3”) is passed through a filter, and then the solvent in step (A) is mainly distilled off under reduced pressure (0.13 kPa) to give a total volume. Was reduced (11% of the original volume). This solution is referred to as “concentrate of reaction solution 3”.
(Process (B2))
As shown in FIG. 1, a Pyrex glass tube (3) having a diameter of 10 mm and a length of 42 cm is used as a reactor, and the portion filled with silica as a catalyst (hereinafter referred to as “catalyst layer”) is electrically supplied from the outside so as to be 350 ° C. Furnace (4) is installed and branched into two lines at the bottom of the reaction tube. Receivers (room temperature) (7) and (13) for acquisition of isocyanate compounds, and receivers for acquisition of methanol ( (Cooled with cold ethanol) Via (9) and (15), both lines were connected to a vacuum pump, and the vacuum lines were connected. Switching between the two lines was performed by opening only one of the valves (5 and 10, and 11 and 16) (closing the other line).
As a catalyst, 2.8 g of FUJI SILICIA CHEMICAL CARTOECT Q50 (average pore size 50 nm, particle size 1.1 to 2.2 mm) is filled in the Pyrex glass tube (3), and the vacuum pump (17) is started. The pressure was reduced to 1.33 kPa, the valve (5) and the valve (10) were opened, the valve (11) and the valve (16) were closed, and the concentrated liquid (1) of the reaction liquid 3 heated and melted at 150 ° C. Was supplied at 2.2 g / h with a syringe pump (2). It heated so that the temperature of a catalyst layer might be 350 degreeC with an electric furnace (4).
The substrate supplied in liquid form from the syringe pump to the reaction tube is vaporized in the vaporization layer at the top of the annular reactor, reacted in the catalyst layer, and converted into the target product. 30 minutes after confirming that the product containing the isocyanate compound condensed in the product heat exchanger (6) began to be collected in the receiver (7), the valves (5) and (10) were closed. The valve (11) and the valve (16) are opened, and the product containing the condensed isocyanate compound is recovered in the receiver (13) and methanol in the receiver (15) for 140 minutes, and is recovered in the receiver (13). The product containing the condensed isocyanate compound was analyzed by liquid chromatography, and the methanol condensed and recovered in the receiver (15) was analyzed by gas chromatography. As a result, the conversion rate was 100%, and 1,3-bis (isocyanatomethyl) cyclohexane as a product was 48% in yield with respect to 1,3-bis (aminomethyl) cyclohexane (selectivity 48% 43%). ), 1-isocyanatomethyl-3-methoxycarbonylaminomethylcyclohexane as an intermediate was obtained in a yield of 6%.

Example 5 (Synthesis of 1,3-bis (isocyanatomethyl) cyclohexane) (Step (A))
In a 200 mL glass container equipped with a stirrer, a thermometer and a cooling device, 10 g (70 mmol) of 1,3-bis (aminomethyl) cyclohexane, 19 g (210 mmol) of dimethyl carbonate, 100 mL of toluene and Candida antarctica 10 g of lipase derived from (Candida antarctica) (Novozym 435 (trade name); manufactured by Novozyme) was added and reacted at 70 ° C. for 15 hours with stirring. After completion of the reaction, the obtained reaction liquid (hereinafter referred to as “reaction liquid 4”) is passed through a filter, and then the solvent in step (A) is mainly distilled off under reduced pressure (0.13 kPa) to obtain a total volume. Was reduced (16% of the original volume). This solution is referred to as “the concentrate of the reaction solution 4”.
(Process (B2))
As shown in FIG. 1, a Pyrex glass tube having a diameter of 10 mm and a length of 42 cm is used as a reactor, and an electric furnace is installed from the outside so that the catalyst layer has a predetermined temperature. Were connected to a vacuum pump via a trap for acquisition of isocyanate (room temperature) and a trap for acquisition of methanol (cooled with cold ethanol) at the bottom of the reaction tube, and a vacuum line was connected. 1.0 g of the catalyst (Ca / SiO ₂ ) prepared in Production Example 3 is filled in the above Pyrex glass tube, depressurized to 1.33 kPa, and the concentrated solution of the reaction solution 4 is 2.2 g / h with a syringe pump. Supplied. It heated so that the temperature of a catalyst layer might be 350 degreeC with an electric furnace. After the reaction system and the composition of the reaction solution were stabilized, the reaction solution was recovered for 40 minutes, and the recovered solution was analyzed by liquid chromatography. As a result, the conversion rate was 100%, and 1,3-bis (isocyanatomethyl) cyclohexane as a product was 73% yield (selectivity 73%) with respect to 1,3-bis (aminomethyl) cyclohexane. 1-isocyanatomethyl-3-methoxycarbonylaminomethylcyclohexane was obtained in a yield of 17%.

Example 6 Synthesis of 1,3-bis (isocyanatomethyl) cyclohexane
(Process (A))
In a 200 mL glass container equipped with a stirrer, a thermometer and a cooling device, 10 g (70 mmol) of 1,3-bis (aminomethyl) cyclohexane, 38 g (420 mmol) of dimethyl carbonate, 54 mL of toluene and Candida antarctica 15 g of lipase derived from (Candida antarctica) (Novozym 435 (trade name); manufactured by Novozyme) was added and reacted at 70 ° C. for 24 hours with stirring. After completion of the reaction, 5.0 g of activated carbon (manufactured by Wako Pure Chemical Industries, Ltd.) was added to the resulting reaction liquid (hereinafter referred to as “reaction liquid 5”), and the mixture was stirred and passed through a filter. After performing the same activated carbon treatment and filtration three times in total, the solvent in step (A) was mainly distilled off under reduced pressure (0.13 kPa) to reduce the total volume (17% of the initial volume). This solution is referred to as “concentrate of reaction solution 5”.
(Process (B2))
As shown in FIG. 1, a Pyrex glass tube having a diameter of 10 mm and a length of 42 cm is used as a reactor, and an electric furnace is installed from the outside so that the catalyst layer has a predetermined temperature. Were connected to a vacuum pump via a trap for acquisition of isocyanate (room temperature) and a trap for acquisition of methanol (cooled with cold ethanol) at the bottom of the reaction tube, and a vacuum line was connected. 1.0 g of the catalyst (Ca / SiO ₂ ) prepared in Production Example 3 is filled in the above Pyrex glass tube, depressurized to 1.33 kPa, and the concentrated solution of reaction solution 5 is 2.2 g / h with a syringe pump. Supplied. It heated so that the temperature of a catalyst layer might be 350 degreeC with an electric furnace. After the reaction system and the composition of the reaction solution were stabilized, the reaction solution was recovered for 40 minutes, and the recovered solution was analyzed by liquid chromatography. As a result, the conversion was 100%, and 1,3-bis (isocyanatomethyl) cyclohexane as the product was 79% yield (selectivity 79%) with respect to 1,3-bis (aminomethyl) cyclohexane. 1-isocyanatomethyl-3-methoxycarbonylaminomethylcyclohexane was obtained in a yield of 9%.

Example 7 (Synthesis of hexamethylene 1,6-diisocyanate)
(Process (A))
In a 200 mL glass container equipped with a stirrer, a thermometer and a cooling device, 10 g (86 mmol) of 1,6-hexamethylenediamine, 47 g (516 mmol) of dimethyl carbonate, 115 mL of toluene and Candida antarctica (Candida antarctica) Lipase 10 g (Novozym 435 (trade name); manufactured by Novozyme) was added and reacted at 70 ° C. for 24 hours with stirring. After completion of the reaction, the obtained reaction solution (hereinafter referred to as “reaction solution 6”) is passed through a filter, and then the solvent in step (A) is mainly distilled off under reduced pressure (0.13 kPa) to obtain a total volume. Was reduced (11% of the original volume). This solution is referred to as “the concentrate of the reaction solution 6”.
(Process (B2))
As shown in FIG. 1, a Pyrex glass tube having a diameter of 10 mm and a length of 42 cm is used as a reactor, and an electric furnace is installed from the outside so that the catalyst layer has a predetermined temperature. Were connected to a vacuum pump via a trap for acquisition of isocyanate (room temperature) and a trap for acquisition of methanol (cooled with cold ethanol) at the bottom of the reaction tube, and a vacuum line was connected. 1.0 g of the catalyst (Ca / SiO ₂ ) prepared in Production Example 3 is filled in the above Pyrex glass tube, the pressure is reduced to 1.33 kPa, and the concentrated solution of the reaction solution 6 is 2.1 g / h with a syringe pump. Supplied. It heated so that the temperature of a catalyst layer might be 350 degreeC with an electric furnace. After the reaction system and the composition of the reaction solution were stabilized, the reaction solution was recovered for 40 minutes, and the recovered solution was analyzed by liquid chromatography. As a result, the conversion rate was 100%, and the product was hexamethylene 1,6-diisocyanate in a yield of 60% (selectivity 60%) with respect to 1,6-hexamethylenediamine, and the intermediate 1-isocyanato- 6-methoxycarbonylaminohexane was obtained with a yield of 16%.

Example 8 (Synthesis of hexamethylene 1,6-diisocyanate)
(Process (A))
In a 200 mL glass container equipped with a stirrer, a thermometer and a cooling device, 10 g (86 mmol) of 1,6-hexamethylenediamine, 47 g (516 mmol) of dimethyl carbonate, 100 mL of toluene, and Candida antarctica (Candida antarctica) Lipase 10 g (Novozym 435 (trade name); manufactured by Novozyme) was added and reacted at 70 ° C. for 24 hours with stirring. After completion of the reaction, 10 g of activated carbon (manufactured by Wako Pure Chemical Industries, Ltd.) was added to the resultant reaction liquid (hereinafter referred to as “reaction liquid 7”), and the mixture was stirred and passed through a filter. The solvent of step (A) was mainly distilled off under reduced pressure (0.13 kPa) to reduce the total volume (11% of the original volume). This solution is referred to as “the concentrate of the reaction solution 7”.
(Process (B2))
As shown in FIG. 1, a Pyrex glass tube having a diameter of 10 mm and a length of 42 cm is used as a reactor, and an electric furnace is installed from the outside so that the catalyst layer has a predetermined temperature. Were connected to a vacuum pump via a trap for acquisition of isocyanate (room temperature) and a trap for acquisition of methanol (cooled with cold ethanol) at the bottom of the reaction tube, and a vacuum line was connected. 1.1 g of the catalyst (Ca / SiO ₂ ) prepared in Production Example 3 is filled in the above Pyrex glass tube, depressurized to 1.33 kPa, and the concentrated solution of reaction solution 7 is 2.1 g / h with a syringe pump. Supplied. It heated so that the temperature of a catalyst layer might be 350 degreeC with an electric furnace. After the composition of the reaction system and the reaction solution was stabilized, the reaction solution was recovered for 60 minutes, and the recovered solution was analyzed by liquid chromatography. As a result, the conversion rate was 100%, and the product was hexamethylene 1,6-diisocyanate in a yield of 61% (selectivity 61%) with respect to 1,6-hexamethylenediamine, and the intermediate 1-isocyanato- 6-methoxycarbonylaminohexane was obtained with a yield of 4%.

Example 9 (Synthesis of n-hexyl isocyanate)
(Process (A))
To a glass container having an internal volume of 250 mL, 25 g (247 mmol) of n-hexylamine, 67 g (741 mmol) of dimethyl carbonate and 155 mL of toluene were added to obtain a uniform solution. A Pyrex glass tube having a diameter of 10 mm and a length of 10 cm is used as a reactor, and this is filled with 1.3 g of lipase derived from Candida antarctica (Novozym 435 (trade name); manufactured by Novozyme), 40 The mixture was heated to 0 ° C., and the homogeneous solution was supplied thereto from the top at 2 mL / h. The obtained reaction solution (hereinafter referred to as “reaction solution 8”) was mainly distilled off the solvent in step (A) under reduced pressure (0.13 kPa) to reduce the total volume (17% of the original volume). ). This solution is referred to as “the concentrated solution of the reaction solution 8”.
(Process (B))
As shown in FIG. 2, a Pyrex glass tube (21) having a diameter of 10 mm and a length of 42 cm is used as a reactor, and electricity is externally applied so that a portion filled with silica as a catalyst (hereinafter referred to as “catalyst layer”) is 350 ° C. A furnace (22) is installed and branched into two lines at the bottom of the reaction tube. Receivers for the acquisition of isocyanate compounds (room temperature) (25) and (30), receivers for the acquisition of methanol ( The outlet was opened to the atmosphere via (27) and (32). Switching between the two lines was performed by opening only one line of the valves (21 and 28) (closing the other line).
As a catalyst, 1.4 g of Carriert Q300 (average pore size: 300 nm, particle size: 1.1 to 2.2 mm) manufactured by Fuji Silysia Chemical Co., Ltd. was filled in the Pyrex glass tube (21), and the carrier was introduced from the top of (21). As a gas, N ₂ (20) was supplied at a flow rate of 30 mL / min. The valve (23) was opened, the valve (28) was closed, and the concentrated liquid (18) of the reaction liquid 8 was supplied at 1.9 g / h by the syringe pump (19). It heated so that the temperature of a catalyst layer might be 350 degreeC with an electric furnace (22).
The substrate supplied in liquid form from the syringe pump to the reaction tube is vaporized in the vaporization layer at the top of the annular reactor, reacted in the catalyst layer, and converted into the target product. 30 minutes after confirming that the product containing the isocyanate compound condensed in the product heat exchanger (24) began to be collected in the receiver (25), the valve (231) was closed and the valve (28) The product containing the condensed isocyanate compound was recovered in the receiver (30) and methanol in the receiver (32) for 40 minutes, and each recovered liquid was analyzed by gas chromatography. As a result, the conversion rate was 100%, and as a product, the yield of n-hexyl isocyanate was 89% with respect to hexylamine (selectivity 94%) and the intermediate methyl n-hexylcarbamate was obtained with a yield of 5%. (Conversion 95%).

Example 10 (Synthesis of n-hexyl isocyanate)
(Process (A))
From a glass container having an internal volume of 200 mL equipped with a stirrer, a thermometer and a cooling device, derived from 10 g (99 mmol) of n-hexylamine, 27 g (296 mmol) of dimethyl carbonate, 63 mL of toluene and Candida antarctica Lipase 5.5g (Novozym 435 (trade name); manufactured by Novozyme) was added and reacted at 70 ° C for 17 hours with stirring. After completion of the reaction, the obtained reaction solution (hereinafter referred to as “reaction solution 9”) is passed through a filter, and then the solvent in step (A) is mainly distilled off under reduced pressure (0.13 kPa) to obtain a total volume. Was reduced (17% of the original volume). This solution is referred to as “a concentrated liquid of the reaction liquid 9”.
(Process (B2))
As shown in FIG. 2, a Pyrex glass tube having a diameter of 10 mm and a length of 42 cm is used as a reactor, an electric furnace is installed from the outside so that the catalyst layer has a predetermined temperature, and a carrier gas (N ₂ ) is placed on the top of the reactor. The concentrated solution supply port of the reaction solution 9 was connected, and a trap (60 ° C. heating) for acquiring isocyanate and a trap (cooling with cold ethanol) for acquiring methanol were installed at the bottom of the reaction tube. 1.0 g of the catalyst (Ca / SiO ₂ ) prepared in Production Example 3 was filled in the Pyrex glass tube, and the carrier gas (N ₂ ) flow rate was 30 mL / min. The concentrate of the reaction liquid 9 was supplied at 1.9 g / h with a syringe pump. It heated so that the temperature of a catalyst layer might be 350 degreeC with an electric furnace. After the reaction system and the composition of the reaction solution were stabilized, the reaction solution was recovered for 30 minutes, and the recovered solution was analyzed by gas chromatography. As a result, the conversion rate was 100%, and as a product, the yield of n-hexyl isocyanate was 85% with respect to hexylamine (selectivity 92%) and the intermediate methyl n-hexylcarbamate was obtained with a yield of 8%. (Conversion 92%).

Example 11 (Synthesis of n-hexyl isocyanate)
(Process (A))
From a glass container having an internal volume of 200 mL equipped with a stirrer, a thermometer and a cooling device, derived from 10 g (99 mmol) of n-hexylamine, 27 g (296 mmol) of dimethyl carbonate, 63 mL of toluene and Candida antarctica Lipase 6g (Novozym 435 (trade name); manufactured by Novozyme) was added and reacted at 70 ° C. for 24 hours with stirring. After completion of the reaction, the obtained reaction solution (hereinafter referred to as “reaction solution 10”) was passed through a filter.
(Process (B2))
As shown in FIG. 2, a Pyrex glass tube having a diameter of 10 mm and a length of 42 cm is used as a reactor, an electric furnace is installed from the outside so that the catalyst layer has a predetermined temperature, and a carrier gas (N ₂ ) is placed on the top of the reactor. The reaction solution 10 supply port was connected, and a trap (room temperature) for obtaining isocyanate and a trap (cooling with cold ethanol) for obtaining methanol were installed at the bottom of the reaction tube. 1.1 g of the catalyst (Ca / SiO ₂ ) prepared in Production Example 3 was filled in the Pyrex glass tube, and the carrier gas (N ₂ ) flow rate was 30 mL / min. The reaction solution 10 was supplied at 1.8 g / h with a syringe pump. It heated so that the temperature of a catalyst layer might be 350 degreeC with an electric furnace. After the composition of the reaction system and the reaction solution was stabilized, the reaction solution was collected for 60 minutes, and the collected solution was analyzed by gas chromatography. As a result, the conversion rate was 100%, and as a product, n-hexyl isocyanate was 84% yield (selectivity 84%) with respect to hexylamine, and the intermediate methyl n-hexylcarbamate was obtained in 4% yield. It was.

Example 12 (Synthesis of 1,3-bis (isocyanatomethyl) cyclohexane)
(Process (A))
In a glass container having an internal volume of 200 mL equipped with a stirrer, a thermometer and a cooling device, 10 g (70 mmol) of 1,3-bis (aminomethyl) cyclohexane, 38 g (422 mmol) of dimethyl carbonate, 54 mL of toluene and Candida antarctica 10 g of lipase derived from (Candida antarctica) (Novozym 435 (trade name); manufactured by Novozyme) was added and reacted at 70 ° C. for 24 hours with stirring. After completion of the reaction, the obtained reaction solution (hereinafter referred to as “reaction solution 11”) was passed through a filter.
(Process (B2))
As shown in FIG. 1, a Pyrex glass tube having a diameter of 10 mm and a length of 42 cm is used as a reactor, an electric furnace is installed from the outside so that the catalyst layer has a predetermined temperature, and a supply port for the reaction solution 11 is provided above the reactor. Were connected to a vacuum pump via a trap (room temperature) for acquiring isocyanate (cooled with cold ethanol) at the bottom of the reaction tube, and a vacuum line was connected. The Pyrex glass tube was filled with 2.2 g of the catalyst (Ca / SiO ₂ ) prepared in Production Example 3, the pressure was reduced to 1.33 kPa, and the reaction solution 11 was supplied at 3.8 g / h with a syringe pump. It heated so that the temperature of a catalyst layer might be 350 degreeC with an electric furnace. After the composition of the reaction system and the reaction solution was stabilized, the reaction solution was recovered for 15 minutes, and the recovered solution was analyzed by liquid chromatography. As a result, the conversion was 100%, and 1,3-bis (isocyanatomethyl) cyclohexane as a product was a yield of 61% (selectivity 61%) with respect to 1,3-bis (aminomethyl) cyclohexane. 1-isocyanatomethyl-3-methoxycarbonylaminomethylcyclohexane was obtained in a yield of 6%.

Example 13 (Synthesis of 1,3-bis (isocyanatomethyl) cyclohexane)
(Process (A))
In a glass container having an internal volume of 200 mL equipped with a stirrer, a thermometer and a cooling device, 10 g (70 mmol) of 1,3-bis (aminomethyl) cyclohexane, 38 g (422 mmol) of dimethyl carbonate, 54 mL of toluene and Candida antarctica 10 g of lipase derived from (Candida antarctica) (Novozym 435 (trade name); manufactured by Novozyme) was added and reacted at 70 ° C. for 24 hours with stirring. After completion of the reaction, the obtained reaction solution (hereinafter referred to as “reaction solution 12”) was passed through a filter.
(Process (B2))
As shown in FIG. 1, a Pyrex glass tube having a diameter of 10 mm and a length of 42 cm is used as a reactor, and an electric furnace is installed from the outside so that the catalyst layer has a predetermined temperature. Were connected to a vacuum pump via a trap (room temperature) for acquiring isocyanate (cooled with cold ethanol) at the bottom of the reaction tube, and a vacuum line was connected. 3.6 g of Carriert Q300 (average pore size 300 nm, particle size 1.1 to 2.2 mm) manufactured by Fuji Silysia Chemical Co., Ltd. as a catalyst was filled in the Pyrex glass tube, and the pressure was reduced to 1.33 kPa. It was supplied at 1.9 g / h with a syringe pump. It heated so that the temperature of a catalyst layer might be 350 degreeC with an electric furnace. After the composition of the reaction system and the reaction solution was stabilized, the reaction solution was recovered for 60 minutes, and the recovered solution was analyzed by liquid chromatography. As a result, the conversion rate was 100%, and the product was 1,3-bis (isocyanatomethyl) cyclohexane with a yield of 58% (selectivity 58%) with respect to 1,3-bis (aminomethyl) cyclohexane. 1-isocyanatomethyl-3-methoxycarbonylaminomethylcyclohexane was obtained in a yield of 1%.

Comparative Example 5 (Synthesis of 1,3-bis (isocyanatomethyl) cyclohexane)
(Process (A))
In a glass container having an internal volume of 200 mL equipped with a stirrer, a thermometer and a cooling device, 10 g (70 mmol) of 1,3-bis (aminomethyl) cyclohexane, 38 g (422 mmol) of dimethyl carbonate, 54 mL of toluene and Candida antarctica 10.0 g of lipase derived from (Candida antarctica) (Novozym 435 (trade name); manufactured by Novozyme) was added and reacted at 70 ° C. for 24 hours with stirring. After completion of the reaction, the obtained reaction solution (hereinafter referred to as “reaction solution 15”) was passed through a filter.
(Process (B2))
As shown in FIG. 1, a Pyrex glass tube having a diameter of 10 mm and a length of 42 cm is used as a reactor, and an electric furnace is installed from the outside so that the catalyst layer has a predetermined temperature. Were connected to a vacuum pump via a trap (room temperature) for acquiring isocyanate (cooled with cold ethanol) at the bottom of the reaction tube, and a vacuum line was connected. The Pyrex glass tube was not filled with a catalyst, the pressure was reduced to 1.33 kPa, and the reaction solution 15 was supplied at 3.8 g / h with a syringe pump. It heated so that the temperature of a catalyst layer might be 350 degreeC with an electric furnace. After the composition of the reaction system and the reaction solution was stabilized, the reaction solution was recovered for 30 minutes, and the recovered solution was analyzed by liquid chromatography. The formation of 1,3-bis (isocyanatomethyl) cyclohexane was not confirmed, and the intermediate 1-isocyanatomethyl-3-methoxycarbonylaminomethylcyclohexane was in contrast to 1,3-bis (aminomethyl) cyclohexane. At a rate of 1%, 1,3-bis (methoxycarbonylaminomethyl) cyclohexane was recovered in a yield of 74%.

Example 14 (Synthesis of n-hexyl isocyanate)
(Process (A))
From a glass container having an internal volume of 200 mL equipped with a stirrer, a thermometer and a cooling device, 10 g (99 mmol) of n-hexylamine, 27 g (296 mmol) of dimethyl carbonate, 63 mL of toluene and Candida antarctica (Candida antarctica) Lipase 6g (Novozym 435 (trade name); manufactured by Novozyme) was added and reacted at 70 ° C. for 7 hours with stirring. After completion of the reaction, 10 g of activated carbon (manufactured by Wako Pure Chemical Industries, Ltd.) was added to the resultant reaction liquid (hereinafter referred to as “reaction liquid 13”), and the mixture was stirred and passed through a filter. This solution is referred to as “reaction liquid 13 treatment liquid”.
(Process (B))
As shown in FIG. 2, a Pyrex glass tube having a diameter of 10 mm and a length of 42 cm is used as a reactor, an electric furnace is installed from the outside so that the catalyst layer has a predetermined temperature, and a carrier gas (N ₂ ) is placed on the top of the reactor. The processing solution supply port for the reaction solution 13 was connected, and a trap (room temperature) for acquiring isocyanate and a trap (cooling with cold ethanol) for acquiring methanol were installed at the bottom of the reaction tube. 1.1 g of the catalyst (Ca / SiO ₂ ) prepared in Production Example 3 was filled in the Pyrex glass tube, and the carrier gas (N ₂ ) flow rate was 30 mL / min. The processing solution of the reaction solution 13 was supplied at 1.8 g / h with a syringe pump. It heated so that the temperature of a catalyst layer might be 350 degreeC with an electric furnace. After the composition of the reaction system and the reaction solution was stabilized, the reaction solution was collected for 60 minutes, and the collected solution was analyzed by gas chromatography. As a result, the conversion was 100%, and n-hexyl isocyanate was obtained as a product in a yield of 54% (selectivity 54%) with respect to hexylamine.

Example 15 (Synthesis of n-hexyl isocyanate)
(Process (A))
From a glass container having an internal volume of 200 mL equipped with a stirrer, a thermometer and a cooling device, 10 g (99 mmol) of n-hexylamine, 27 g (296 mmol) of dimethyl carbonate, 63 mL of toluene and Candida antarctica (Candida antarctica) Lipase 6g (Novozym 435 (trade name); manufactured by Novozyme) was added and reacted at 70 ° C. for 7 hours with stirring. After completion of the reaction, 5.0 g of activated carbon (manufactured by Wako Pure Chemical Industries, Ltd.) was added to the resulting reaction liquid (hereinafter referred to as “reaction liquid 14”), stirred, passed through a filter, and then under reduced pressure (0. At 13 kPa), the solvent in step (A) was mainly distilled off to reduce the total volume (17% of the original volume). This solution is referred to as “the concentrate of the reaction solution 14”.
(Process (B))
As shown in FIG. 2, a Pyrex glass tube having a diameter of 10 mm and a length of 42 cm is used as a reactor, an electric furnace is installed from the outside so that the catalyst layer has a predetermined temperature, and a carrier gas (N ₂ ) is placed on the top of the reactor. And the supply port of the reaction solution 14 was connected, and a trap (room temperature) for obtaining isocyanate and a trap (cooling with cold ethanol) for obtaining methanol were installed at the bottom of the reaction tube. 1.1 g of the catalyst (Ca / SiO ₂ ) prepared in Production Example 3 was filled in the Pyrex glass tube, and the carrier gas (N ₂ ) flow rate was 30 mL / min. The reaction solution 14 was supplied at 1.9 g / h with a syringe pump. It heated so that the temperature of a catalyst layer might be 350 degreeC with an electric furnace. After the composition of the reaction system and the reaction solution was stabilized, the reaction solution was collected for 60 minutes, and the collected solution was analyzed by gas chromatography. As a result, the conversion rate was 100%, the product was n-hexyl isocyanate with a yield of 74% (selectivity 74%) with respect to hexylamine, and the intermediate methyl n-hexylcarbamate was obtained with a yield of 16%. It was.

Example 17 (Synthesis of n-hexyl isocyanate)
(Process (A))
In a glass container having an internal volume of 200 mL equipped with a stirrer, a thermometer and a cooling device, 10 g (99 mmol) of n-hexylamine, 27 g (297 mmol) of dimethyl carbonate and 5 g of lipase derived from Candida antarctica ( Novozym 435 (trade name); manufactured by Novozyme) was added and reacted at 70 ° C. for 14 hours with stirring. After completion of the reaction, the obtained reaction solution (hereinafter referred to as “reaction solution 18”) was passed through a filter.
(Process (B2))
As shown in FIG. 2, a Pyrex glass tube having a diameter of 10 mm and a length of 42 cm is used as a reactor, an electric furnace is installed from the outside so that the catalyst layer has a predetermined temperature, and a carrier gas (N ₂ ) is placed on the top of the reactor. And a supply port for the reaction liquid 18 were connected, and a trap (at room temperature) for acquiring isocyanate and a trap (for cooling with cold ethanol) for acquiring methanol were installed at the bottom of the reaction tube. 1.1 g of the catalyst (Ca / SiO ₂ ) prepared in Production Example 3 was filled in the Pyrex glass tube, and the carrier gas (N ₂ ) flow rate was 30 mL / min. The reaction solution 18 was supplied at 1.9 g / h with a syringe pump. It heated so that the temperature of a catalyst layer might be 350 degreeC with an electric furnace. After the reaction system and the composition of the reaction solution were stabilized, the reaction solution was recovered for 30 minutes, and the recovered solution was analyzed by gas chromatography. As a result, the conversion rate was 100%, and as a product, the yield of n-hexyl isocyanate was 55% with respect to hexylamine (selectivity 55%) and the intermediate methyl n-hexylcarbamate was obtained with a yield of 8%. It was.

Example 18 (Synthesis of n-hexyl isocyanate)
(Process (A))
In a glass container having an internal volume of 200 mL equipped with a stirrer, a thermometer and a cooling device, 10 g (99 mmol) of n-hexylamine, 27 g (297 mmol) of dimethyl carbonate and 5 g of lipase derived from Candida antarctica ( Novozym 435 (trade name); manufactured by Novozyme) was added and reacted at 70 ° C. for 14 hours with stirring. After completion of the reaction, the obtained reaction liquid (hereinafter referred to as “reaction liquid 19”) is passed through a filter, and then the solvent in step (A) is mainly distilled off under reduced pressure (0.13 kPa) to obtain a total volume. Was reduced (47% of the original volume). This solution is referred to as “the concentrated solution of the reaction solution 19”.
(Process (B2))
As shown in FIG. 2, a Pyrex glass tube having a diameter of 10 mm and a length of 42 cm is used as a reactor, an electric furnace is installed from the outside so that the catalyst layer has a predetermined temperature, and a carrier gas (N ₂ ) is placed on the top of the reactor. The concentrated solution supply port of the reaction solution 19 was connected, and a trap for obtaining isocyanate (heating at 60 ° C.) and a trap for obtaining methanol (cooled with cold ethanol) were installed at the bottom of the reaction tube. 1.0 g of the catalyst (Ca / SiO ₂ ) prepared in Production Example 3 was filled in the Pyrex glass tube, and the carrier gas (N ₂ ) flow rate was 30 mL / min. The concentrate of the reaction liquid 19 was supplied at 1.9 g / h with a syringe pump. It heated so that the temperature of a catalyst layer might be 350 degreeC with an electric furnace. After the composition of the reaction system and the reaction solution was stabilized, the reaction solution was collected for 60 minutes, and the collected solution was analyzed by gas chromatography. As a result, the conversion rate was 100%, the product was n-hexyl isocyanate with a yield of 47% based on hexylamine (selectivity 47%), and the intermediate methyl n-hexylcarbamate was obtained with a yield of 44%. It was.

Example 19 (Synthesis of n-hexyl isocyanate)
(Process (A))
In a glass container having an internal volume of 200 mL equipped with a stirrer, a thermometer and a cooling device, 10 g (99 mmol) of n-hexylamine, 27 g (297 mmol) of dimethyl carbonate and 5 g of lipase derived from Candida antarctica ( Novozym 435 (trade name); manufactured by Novozyme) was added and reacted at 70 ° C. for 14 hours with stirring. After completion of the reaction, the obtained reaction solution (hereinafter referred to as “reaction solution 20”) is passed through a filter, and then the solvent in step (A) is mainly distilled off under reduced pressure (0.13 kPa) to give a total volume. (44% of the original volume). This solution is referred to as “the concentrate of the reaction solution 20”.
(Process (B2))
As shown in FIG. 2, a Pyrex glass tube having a diameter of 10 mm and a length of 42 cm is used as a reactor, an electric furnace is installed from the outside so that the catalyst layer has a predetermined temperature, and a carrier gas (N ₂ ) is placed on the top of the reactor. The concentrated solution supply port of the reaction solution 20 was connected, and a trap (60 ° C. heating) for acquiring isocyanate and a trap (cooling with cold ethanol) for acquiring methanol were installed at the bottom of the reaction tube. As a catalyst, 3.7 g of Carriert Q300 (average pore size 300 nm, particle size 1.1 to 2.2 mm) manufactured by Fuji Silysia Chemical Co., Ltd. was filled in the above Pyrex glass tube, and a carrier gas (N ₂ ) flow rate of 30 mL / min. The concentrate of the reaction solution 20 was supplied at 1.9 g / h with a syringe pump. It heated so that the temperature of a catalyst layer might be 350 degreeC with an electric furnace. After the composition of the reaction system and the reaction solution was stabilized, the reaction solution was collected for 60 minutes, and the collected solution was analyzed by gas chromatography. As a result, the conversion rate was 100%, the product was n-hexyl isocyanate with a yield of 22% based on hexylamine (selectivity 22%), and the intermediate methyl n-hexylcarbamate was obtained with a yield of 23%. It was.

Comparative Example 6 (Synthesis of n-hexyl isocyanate)
(Process (A))
From a glass container having an internal volume of 200 mL equipped with a stirrer, a thermometer and a cooling device, derived from 10 g (99 mmol) of n-hexylamine, 27 g (296 mmol) of dimethyl carbonate, 63 mL of toluene and Candida antarctica Lipase 5.5g (Novozym 435 (trade name); manufactured by Novozyme) was added and reacted at 70 ° C for 17 hours with stirring. After completion of the reaction, the obtained reaction solution (hereinafter referred to as “reaction solution 16”) is passed through a filter, and then the solvent in step (A) is mainly distilled off under reduced pressure (0.13 kPa) to give a total volume. Was reduced (17% of the original volume). This solution is referred to as “the concentrate of the reaction solution 16”.
(Process (B2))
As shown in FIG. 2, the diameter 10 mm, and the reactor Pyrex glass tube of length 42cm, the catalyst layer is placed an electric furnace from the outside to a predetermined temperature, reactor top in a carrier gas (N ₂₎ The concentrated solution supply port of the reaction solution 16 was connected, and a trap for obtaining isocyanate (heating at 60 ° C.) and a trap for obtaining methanol (cooled with cold ethanol) were installed at the bottom of the reaction tube. The Pyrex glass tube is not filled with a catalyst, and a carrier gas (N ₂ ) flow rate of 30 mL / min. The reaction solution 16 was supplied at 1.9 g / h with a syringe pump. It heated so that the temperature of a catalyst layer might be 350 degreeC with an electric furnace. After the composition of the reaction system and the reaction solution was stabilized, the reaction solution was collected for 60 minutes, and the collected solution was analyzed by gas chromatography. As a result, a conversion rate of 100%, n-hexyl isocyanate as a product was obtained in a yield of 4% with respect to hexylamine (selectivity 4%), and an intermediate methyl n-hexylcarbamate was obtained in a yield of 99%. It was.

Comparative Example 7 (Synthesis of 1,3-bis (isocyanatomethyl) cyclohexane)
(Process (A))
In a glass container having an internal volume of 1000 mL equipped with a stirrer, a thermometer and a cooling device, 71 g (497 mmol) of 1,3-bis (aminomethyl) cyclohexane, 282 g (3100 mmol) of dimethyl carbonate and sodium methoxide (28% methanol solution) ) 4.5 mL was added and reacted at 70 ° C. for 4 hours with stirring. After completion of the reaction, the resulting reaction solution was concentrated under reduced pressure and then vacuum dried to obtain white crystals. This white crystal is referred to as “Reactant 1”.
(Process (B2))
As shown in FIG. 1, a Pyrex glass tube having a diameter of 10 mm and a length of 42 cm is used as a reactor, and an electric furnace is installed from the outside so that the catalyst layer has a predetermined temperature. Were connected to a vacuum pump via a trap (room temperature) for acquiring isocyanate (cooled with cold ethanol) at the bottom of the reaction tube, and a vacuum line was connected. As a catalyst, 2.8 g of FUJITILICA CHEMICAL CARTOECT Q50 (average pore size 50 nm, particle size 1.1 to 2.2 mm) is filled in the above Pyrex glass tube, decompressed to 1.33 kPa, and heated at 150 ° C. The melted reaction product 1 was supplied at 2.2 g / h with a syringe pump. However, a white solid was deposited on the top of the reaction tube, and the reaction could not be carried out.

Comparative Example 8 (Synthesis of n-hexyl isocyanate)
(Process (A))
To a glass container having an internal volume of 200 mL equipped with a stirrer, a thermometer and a cooling device, 19 g (189 mmol) of n-hexylamine, 69 g (763 mmol) of dimethyl carbonate and 0.8 mL of sodium methoxide (28% methanol solution) were added. The mixture was reacted at 55 ° C. for 4 hours with stirring. After completion of the reaction, the resulting reaction liquid (hereinafter referred to as “reaction liquid 21”) was reduced in volume by reducing mainly the solvent in the step (A) under reduced pressure (0.13 kPa) (the original volume). 36% of volume). This solution is referred to as “the concentrate of the reaction solution 21”.
(Process (B2))
As shown in FIG. 2, a Pyrex glass tube having a diameter of 10 mm and a length of 42 cm is used as a reactor, an electric furnace is installed from the outside so that the catalyst layer has a predetermined temperature, and a carrier gas (N ₂ ) is placed on the top of the reactor. The concentrated solution supply port of the reaction solution 21 was connected, and a trap for obtaining isocyanate (heating at 60 ° C.) and a trap for obtaining methanol (cooled with cold ethanol) were installed at the bottom of the reaction tube. As a catalyst, 3.7 g of Carriert Q300 (average pore size 300 nm, particle size 1.1 to 2.2 mm) manufactured by Fuji Silysia Chemical Co., Ltd. was filled in the above Pyrex glass tube, and a carrier gas (N ₂ ) flow rate of 30 mL / min. The concentrate of the reaction solution 21 was supplied at 1.9 g / h with a syringe pump. It heated so that the temperature of a catalyst layer might be 350 degreeC with an electric furnace. The substrate supplied in liquid form from the syringe pump to the reaction tube is vaporized in the vaporization layer at the top of the reaction tube, reacted in the catalyst layer, and converted into the target product. After the liquid target was constantly collected by the isocyanate acquisition trap, the reaction solution was collected for 40 minutes, and the collected solution was analyzed by gas chromatography. As a result, the conversion rate was 100%, the product was n-hexyl isocyanate with a yield of 4% based on hexylamine (selectivity 4%), and the intermediate methyl n-hexylcarbamate was obtained with a yield of 17%. It was.

Comparative Example 9 (Synthesis of n-hexyl isocyanate)
(Process (A))
In a glass container having an internal volume of 200 mL equipped with a stirrer, a thermometer and a cooling device, 10 g (99 mmol) of n-hexylamine, 27 g (296 mmol) of dimethyl carbonate and 5 g of lipase derived from Candida antarctica ( Novozym 435 (trade name); manufactured by Novozyme) was added and reacted at 70 ° C. for 16 hours with stirring. After completion of the reaction, the obtained reaction solution (hereinafter referred to as “reaction solution 23”) is passed through a filter, and then the solvent in step (A) is mainly distilled off under reduced pressure (0.13 kPa) to give a total volume. (44% of the original volume). This solution is referred to as “the concentrate of the reaction solution 23”.
(Process (B2))
As shown in FIG. 2, a Pyrex glass tube having a diameter of 10 mm and a length of 42 cm is used as a reactor, an electric furnace is installed from the outside so that the catalyst layer has a predetermined temperature, and a carrier gas (N ₂ ) is placed on the top of the reactor. The concentrated solution supply port of the reaction solution 23 was connected, and a trap (60 ° C. heating) for acquiring isocyanate and a trap (cooling with cold ethanol) for acquiring methanol were installed at the bottom of the reaction tube. As a catalyst, 1.0 g of CaO (manufactured by Wako Pure Chemical Industries, Ltd.) was filled in the above Pyrex glass tube, and a carrier gas (N ₂ ) flow rate of 30 mL / min. The concentrate of the reaction solution 23 was supplied at 1.9 g / h with a syringe pump. It heated so that the temperature of a catalyst layer might be 350 degreeC with an electric furnace. The substrate supplied in liquid form from the syringe pump to the reaction tube is vaporized in the vaporization layer at the top of the reaction tube, reacted in the catalyst layer, and converted into the target product. After the liquid target was constantly collected by the isocyanate acquisition trap, the reaction solution was collected for 60 minutes, and the collected solution was analyzed by gas chromatography. As a result, the conversion rate was 100%, the target product n-hexyl isocyanate was not obtained, and the by-product hexyl urea was obtained with a yield of 100% based on hexylamine.

Comparative Example 10 (Synthesis of n-hexyl isocyanate)
(Process (A))
In a glass container having an internal volume of 200 mL equipped with a stirrer, a thermometer and a cooling device, 10 g (99 mmol) of n-hexylamine, 27 g (296 mmol) of dimethyl carbonate and 5 g of lipase derived from Candida antarctica ( Novozym 435 (trade name); manufactured by Novozyme) was added and reacted at 70 ° C. for 16 hours with stirring. After completion of the reaction, the obtained reaction solution (hereinafter referred to as “reaction solution 24”) is passed through a filter, and then the solvent in step (A) is mainly distilled off under reduced pressure (0.13 kPa) to give a total volume. (44% of the original volume). This solution is referred to as “the concentrate of the reaction solution 24”.
(Process (B2))
As shown in FIG. 2, a Pyrex glass tube having a diameter of 10 mm and a length of 42 cm is used as a reactor, an electric furnace is installed from the outside so that the catalyst layer has a predetermined temperature, and a carrier gas (N ₂ ) is placed on the top of the reactor. The concentrated solution supply port of the reaction solution 24 was connected, and a trap (60 ° C. heating) for acquiring isocyanate and a trap (cooling with cold ethanol) for acquiring methanol were installed at the bottom of the reaction tube. The Pyrex glass tube is not filled with a catalyst, and a carrier gas (N ₂ ) flow rate of 30 mL / min. The concentrate of the reaction solution 24 was supplied at 1.9 g / h with a syringe pump. It heated so that the temperature of a catalyst layer might be 350 degreeC with an electric furnace. The substrate supplied in liquid form from the syringe pump to the reaction tube is vaporized in the vaporization layer at the top of the reaction tube, reacted in the catalyst layer, and converted into the target product. After the liquid target was constantly collected by the isocyanate acquisition trap, the reaction solution was collected for 60 minutes, and the collected solution was analyzed by gas chromatography. As a result, a conversion rate of 100% and methyl n-hexylcarbamate as an intermediate were obtained with a yield of 100%.

  From the above results, an isocyanate compound could be produced directly or continuously from an amine compound and a carbonate compound without isolating and purifying the carbamate compound produced as an intermediate.

Synthesis of Isocyanate Compound from Carbamate Compound In the following, the dicarbamate conversion rate, the diisocyanate and monoisocyanate selectivity, and the yield of diisocyanate and monoisocyanate were calculated using the following formulas.
Dicarbamate conversion rate (%) =
(Converted dicarbamate) / (supplied dicarbamate) × 100
Selectivity of diisocyanate and monoisocyanate =
(Acquired diisocyanate and monoisocyanate) / (converted dicarbamate) × 100
Yield of diisocyanate and monoisocyanate =
(Diisocyanate and monoisocyanate produced) / (Supplied dicarbamate) × 100

Example 20 (Production of 1,3-bis (isocyanatomethyl) cyclohexane by thermal decomposition of 1,3-bis (methoxycarbonylaminomethyl) cyclohexane)
As shown in FIG. 1, a Pyrex glass tube (3) having a diameter of 10 mm and a length of 42 cm is used as a reactor, and the portion filled with silica as a catalyst (hereinafter referred to as “catalyst layer”) is electrically supplied from the outside so as to be 350 ° C. Furnace (4) is installed and branched into two lines at the bottom of the reaction tube. Receivers (room temperature) (7) and (13) for acquisition of isocyanate compounds, and receivers for acquisition of methanol ( (Cooled with cold ethanol) Via (9) and (15), both lines were connected to a vacuum pump, and the vacuum lines were connected. Switching between the two lines was performed by opening only one of the valves (5 and 10, and 11 and 16) (closing the other line).
As a catalyst, 2.3 g of Carriert Q300 (average pore size 300 nm, particle size 1.1 to 2.2 mm) manufactured by Fuji Silysia Chemical Co., Ltd. was filled in the Pyrex glass tube (3), and the vacuum pump (17) was started. The pressure was reduced to 1.33 kPa, the valves (5) and (10) were opened, the valves (11) and (16) were closed, and 1,3-bis (methoxycarbonylamino) heated and melted at 150 ° C. Methyl) cyclohexane (1) was supplied at 2.2 g / h with a syringe pump (2). It heated so that the temperature of a catalyst layer might be 350 degreeC with an electric furnace (4).
30 minutes after confirming that the product containing the condensed isocyanate compound began to be collected in the receiver (7), the valves (5) and (10) were closed, and the valves (11) and (16 ) Is opened, the product containing the condensed isocyanate compound is collected in the receiver (13), methanol is collected in the receiver (15) for 30 minutes, and the product containing the condensed isocyanate compound is collected in the receiver (13). The product was condensed in a receiver (15) by liquid chromatography and the methanol recovered was analyzed by gas chromatography to calculate the dicarbamate conversion rate, diisocyanate and monoisocyanate selectivity and yield.
As products, 1,3-bis (isocyanatomethyl) cyclohexane was obtained in 88% yield (selectivity 88%), and monoisocyanate was obtained in 6% yield.

Example 21 (Production of 1,3-bis (isocyanatomethyl) cyclohexane by thermal decomposition of 1,3-bis (methoxycarbonylaminomethyl) cyclohexane)
As a catalyst, 2.7 g of Carriert Q10 manufactured by Fuji Silysia Chemical Co., Ltd. (average pore size 10 nm, particle size 1.1 to 2.2 mm) was filled in a Pyrex glass tube in the same manner as in Example 20 to 1.33 kPa. 1,3-bis (methoxycarbonylaminomethyl) cyclohexane decompressed and heated and melted at 150 ° C. was supplied at 2.2 g / h with a syringe pump. It heated so that the temperature of a catalyst layer might be 350 degreeC with an electric furnace.
In the same manner as in Example 20, the reaction solution was collected for 30 minutes, and the collected solution was analyzed by liquid chromatography. As products, 1,3-bis (isocyanatomethyl) cyclohexane was obtained in a yield of 72% (selectivity 72%), and monoisocyanate was obtained in a yield of 4%.

Example 22 (Production of 1,3-bis (isocyanatomethyl) cyclohexane by thermal decomposition of 1,3-bis (methoxycarbonylaminomethyl) cyclohexane)
As a catalyst, 2.7 g of Carriert Q50 (average pore size 50 nm, particle size 1.1 to 2.2 mm) manufactured by Fuji Silysia Chemical Co., Ltd. was filled into a Pyrex glass tube in the same manner as in Example 20 to 1.33 kPa. 1,3-bis (methoxycarbonylaminomethyl) cyclohexane decompressed and heated and melted at 150 ° C. was supplied at 2.2 g / h with a syringe pump. It heated so that the temperature of a catalyst layer might be 350 degreeC with an electric furnace.
In the same manner as in Example 20, the reaction solution was collected for 30 minutes, and the collected solution was analyzed by liquid chromatography. As a product, 1,3-bis (isocyanatomethyl) cyclohexane was obtained in 80% yield (selectivity 80%), and monoisocyanate was obtained in 4% yield.

Example 23 (Production of isophorone diisocyanate by thermal decomposition of isophorone dimethyl carbamate (1- (methoxycarbonylamino) -3,3,5-trimethyl-5- (methoxycarbonylaminomethyl) -cyclohexane))
As a catalyst, 1.5 g of FUJI CITIZEN CHEMICAL CARTOECT Q50 (average pore size 50 nm, particle size 1.1 to 2.2 mm) was filled in a Pyrex glass tube in the same manner as in Example 20 to 1.33 kPa. Isophorone dimethyl carbamate (1- (methoxycarbonylamino) -3,3,5-trimethyl-5- (methoxycarbonylaminomethyl) -cyclohexane), which was decompressed and heated and melted at 150 ° C., was 2.1 g / supplied in h. It heated so that the temperature of a catalyst layer might be 350 degreeC with an electric furnace.
In the same manner as in Example 20, the reaction solution was collected for 30 minutes, and the collected solution was analyzed by liquid chromatography. As products, isophorone diisocyanate was obtained in a yield of 87% (selectivity 87%), and monoisocyanate was obtained in a yield of 3%.

Example 24 (Production of isophorone diisocyanate by thermal decomposition of isophorone dimethyl carbamate (1- (methoxycarbonylamino) -3,3,5-trimethyl-5- (methoxycarbonylaminomethyl) -cyclohexane))
As a catalyst, 1.3 g of Carriert Q10 (average pore diameter of 10 nm, particle diameter of 1.1 to 2.2 mm) manufactured by Fuji Silysia Chemical Co., Ltd. was filled in a Pyrex glass tube in the same manner as in Example 20 to 1.33 kPa. Isophorone dimethyl carbamate (1- (methoxycarbonylamino) -3,3,5-trimethyl-5- (methoxycarbonylaminomethyl) -cyclohexane), which was decompressed and heated and melted at 150 ° C., was 2.1 g / supplied in h. It heated so that the temperature of a catalyst layer might be 350 degreeC with an electric furnace.
In the same manner as in Example 20, the reaction solution was collected for 30 minutes, and the collected solution was analyzed by liquid chromatography. As products, isophorone diisocyanate was obtained in a yield of 76% (selectivity 76%), and monoisocyanate was obtained in a yield of 2%.

Example 25 (Production of isophorone diisocyanate by thermal decomposition of isophorone dimethyl carbamate (1- (methoxycarbonylamino) -3,3,5-trimethyl-5- (methoxycarbonylaminomethyl) -cyclohexane))
As a catalyst, 3.2 g of Carriert Q300 (average pore size 300 nm, particle size 1.1 to 2.2 mm) manufactured by Fuji Silysia Chemical Co., Ltd. was filled into a Pyrex glass tube in the same manner as in Example 20 to 1.33 kPa. Isophorone dimethyl carbamate (1- (methoxycarbonylamino) -3,3,5-trimethyl-5- (methoxycarbonylaminomethyl) -cyclohexane), which was decompressed and heated and melted at 150 ° C., was 2.1 g / supplied in h. It heated so that the temperature of a catalyst layer might be 350 degreeC with an electric furnace.
In the same manner as in Example 20, the reaction solution was collected for 30 minutes, and the collected solution was analyzed by liquid chromatography. As products, isophorone diisocyanate was obtained in a yield of 98% (selectivity 98%), and monoisocyanate was obtained in a yield of 2%.

Example 26 (Production of hexamethylene 1,6-diisocyanate by thermal decomposition of 1,6-bis (methoxycarbonylamino) hexane)
As a catalyst, 2.3 g of Carriert Q300 (average pore size: 300 nm, particle size: 1.1 to 2.2 mm) manufactured by Fuji Silysia Chemical Co., Ltd. was filled in a Pyrex glass tube in the same manner as in Example 20 to 1.33 kPa. 1,6-bis (methoxycarbonylamino) hexane, which was decompressed and heated and melted at 150 ° C., was supplied by a syringe pump at 2.1 g / h. It heated so that the temperature of a catalyst layer might be 350 degreeC with an electric furnace.
In the same manner as in Example 20, the reaction solution was collected for 30 minutes, and the collected solution was analyzed by liquid chromatography. As products, hexamethylene 1,6-diisocyanate was obtained in 92% yield (selectivity 92%), and monoisocyanate was obtained in 3% yield.

Example 27 (Production of 2,4-tolylene diisocyanate by thermal decomposition of 2,4-bis (methoxycarbonylamino) toluene)
As a catalyst, 2.3 g of Carriert Q300 (average pore size: 300 nm, particle size: 1.1 to 2.2 mm) manufactured by Fuji Silysia Chemical Co., Ltd. was filled in a Pyrex glass tube in the same manner as in Example 20 to 1.33 kPa. 2,4-bis (methoxycarbonylamino) toluene, which was decompressed and heated and melted at 190 ° C., was supplied at 2.2 g / h with a syringe pump. It heated so that the temperature of a catalyst layer might be 350 degreeC with an electric furnace.
In the same manner as in Example 20, the reaction solution was collected for 30 minutes, and the collected solution was analyzed by liquid chromatography. As a product, 2,4-tolylene diisocyanate was obtained in a yield of 87% (selectivity: 87%), and a monoisocyanate was obtained in a yield of 3%.

Production Example 4 (Preparation of porous silica catalyst)
30.0 g of water and 1.8 g of polyethylene glycol (manufactured by Wako Pure Chemical Industries, Ltd., average molecular weight 20,000) were mixed and stirred in a polyethylene container to obtain a uniform solution. To this, 30 mL of tetraethyl orthosilicate and 2.9 g of a 60% nitric acid aqueous solution (manufactured by Wako Pure Chemical Industries, Ltd.) were added, sealed and vigorously stirred for 1 hour. The gel was further allowed to stand at 50 ° C. for 12 hours, and the produced gel was taken out, washed with purified water, dried at 110 ° C. for 12 hours, and baked in air at 600 ° C. for 2 hours to obtain 7.6 g of silica gel. Measurement of average pore diameter by mercury porosimetry is performed using Quanta Chrome Co. A fully automatic pore distribution measuring device (Pore Master 60-GT) manufactured by using a 0.5 cc (10φ × 30 mm) small cell as a cell was performed.
Using a sample of 281 mg, pore diameter distribution measurement was performed with a mercury contact angle of 140 ° and a mercury surface tension of 480 dyn / cm.
The average pore diameter determined by the above method was 5.1 μm. This was pulverized in a mortar and sieved to a particle size range of 1 mm to 2 mm.

Example 28 (Production of 1,3-bis (isocyanatomethyl) cyclohexane by thermal decomposition of 1,3-bis (methoxycarbonylaminomethyl) cyclohexane)
In the same manner as in Example 20, 3.4 g of the catalyst prepared in Production Example 4 was filled into a Pyrex glass tube, decompressed to 1.33 kPa, and heated and melted at 150 ° C. to 1,3-bis (methoxycarbonylaminomethyl). ) Cyclohexane was supplied at 2.2 g / h with a syringe pump. It heated so that the temperature of a catalyst layer might be 350 degreeC with an electric furnace.
In the same manner as in Example 20, the reaction solution was collected for 30 minutes, and the collected solution was analyzed by liquid chromatography. As a product, 1,3-bis (isocyanatomethyl) cyclohexane was obtained in a yield of 3% and monoisocyanate was obtained in a yield of 34%, and 63% of the raw material 1,3-bis (methoxycarbonylaminomethyl) cyclohexane. Was recovered as an unreacted component (conversion rate 37%).

Production Example 5 (Preparation of porous silica catalyst)
283.3 g of water, 5.2 g (14.35 mmol) of hexadecyltrimethylammonium bromide, 19.2 g of 28% aqueous ammonia solution and 20 mL of tetraethyl orthosilicate were mixed in a polypropylene container and stirred for 12 hours. The produced precipitate was separated by filtration, washed with purified water, dried at 110 ° C. for 12 hours, and calcined in air at 550 ° C. for 4 hours to obtain 6.0 g of silica gel. Nitrogen adsorption measurement was performed using an automatic specific surface area / pore diameter distribution measuring device BELSORP-miniII manufactured by Nippon Bell Co., Ltd. as a measuring device and a pellet cell having a cell outer diameter of 1.8 cm ³ and a stem outer diameter of 9 mm. After 90 mg of the sample was vacuum degassed at 300 ° C. for 1 hour, nitrogen adsorption was performed at 77 K (liquid nitrogen temperature), pore size distribution analysis was performed by the BJH method, and the average pore size was calculated. The average pore diameter determined by the above method was 2.7 nm. This was pulverized in a mortar and sieved to a particle size range of 1 mm to 2 mm.

Example 29 (Production of 1,3-bis (isocyanatomethyl) cyclohexane by thermal decomposition of 1,3-bis (methoxycarbonylaminomethyl) cyclohexane)
In the same manner as in Example 20, 0.5 g of the catalyst prepared in Production Example 5 was charged into a Pyrex glass tube, decompressed to 1.33 kPa, and heated and melted at 150 ° C. to 1,3-bis (methoxycarbonylaminomethyl). ) Cyclohexane was supplied at 2.2 g / h with a syringe pump. It heated so that the temperature of a catalyst layer might be 350 degreeC with an electric furnace.
In the same manner as in Example 20, 1,3-bis (isocyanatomethyl) cyclohexane was obtained as a product in a yield of 25% and monoisocyanate was obtained in a yield of 32%. Carbonylaminomethyl) cyclohexane 7% was recovered as unreacted fraction (conversion 93%).

Production Example 6 (Preparation of porous silica catalyst (Si-ZSM-5))
30 mL of tetraethyl orthosilicate, 30.4 g of 20 to 25% tetrapropylammonium hydroxide aqueous solution, 36.7 g of water and 64.2 g of ethanol were mixed in a polypropylene container and stirred for 2 hours. This was transferred into a 300 mL autoclave with a Teflon inner tube, sealed, and hydrothermally synthesized at 105 ° C. for 100 hours while rotating the autoclave at 50 rpm. The produced precipitate was obtained by centrifugation, washed with purified water, dried at 110 ° C. for 12 hours, and baked in air at 540 ° C. for 4 hours to obtain 6.0 g of silica gel. The nitrogen adsorption measurement was performed using a Quantachrome. Co fully automatic gas adsorption amount measuring device Autosorb-1-MP-9 as a measuring device and a pellet cell having a cell diameter of 1.8 cm ³ and a stem outer diameter of 6 mm. A 50 mg sample was vacuum degassed at 300 ° C. for 1 hour, and then nitrogen adsorption was performed at 77 K (liquid nitrogen temperature). The average pore diameter determined by the above method was 0.5 nm. This was pulverized in a mortar and sieved to a particle size range of 1 mm to 2 mm.

Example 30 (Production of 1,3-bis (isocyanatomethyl) cyclohexane by thermal decomposition of 1,3-bis (methoxycarbonylaminomethyl) cyclohexane)
In the same manner as in Example 20, 0.9 g of the catalyst prepared in Production Example 6 was charged into a Pyrex glass tube, decompressed to 1.33 kPa, and heated and melted at 150 ° C. to 1,3-bis (methoxycarbonylaminomethyl). ) Cyclohexane was supplied at 2.2 g / h with a syringe pump. It heated so that the temperature of a catalyst layer might be 350 degreeC with an electric furnace.
In the same manner as in Example 20, the reaction solution was collected for 30 minutes, and the collected solution was analyzed by liquid chromatography. As a product, 1,3-bis (isocyanatomethyl) cyclohexane was obtained in a yield of 51%, monoisocyanate was obtained in a yield of 18%, and 2% of 1,3-bis (methoxycarbonylaminomethyl) cyclohexane as a raw material was obtained. It was recovered as an unreacted component (conversion rate 98%).

  According to the present invention, an isocyanate compound can be produced directly or continuously from an amine compound and a carbonate compound without isolating and purifying a carbamate compound produced as an intermediate.

[Explanation of symbols]
DESCRIPTION OF SYMBOLS 1 Raw material tank 2 Substrate supply pump 3 Tubular reactor 3a filled with catalyst Evaporation layer (quartz filling)
3b Catalyst layer 4 Heat source for heating the reactor (tubular electric furnace)
5 Valve 6 Product heat exchanger 7 Receiver 8 for collecting the isocyanate compound of the condensed product 8 Heat exchanger for alcohol condensation 9 Receiver 10 for alcohol acquisition Valve 11 Valve 12 Product heat exchanger 13 Condensation Receiving unit 14 for recovering the isocyanate compound of the produced product Heat exchanger 15 for condensing alcohol 16 Receiving unit 16 for alcohol acquisition Valve 17 Vacuum pump 18 Raw material tank 19 Substrate supply pump 20 Inert gas 21 Tubular filled with catalyst Reactor 22 Heat source for heating the reactor (tubular electric furnace, etc.)
23 Valve 24 Product heat exchanger 25 Receiver 26 for recovering condensed product isocyanate compound 26 Heat exchanger 27 for alcohol condensation 28 Receiver 29 for alcohol acquisition Valve 29 Product heat exchanger 30 Condensed product Receiving unit 31 for collecting isocyanate compounds of the product Heat exchanger 32 for condensing alcohol 32 Receiving unit for alcohol acquisition

Claims (21)

(A) General formula (1) in the presence of an enzyme:

(Where
R ¹ represents a hydrocarbon group which may have a substituent,
n represents an integer of 1 to 4) and the general formula (2):

(Wherein R ² independently represents a hydrocarbon group which may have a substituent) and a step of reacting with a carbonate compound represented by (B) (B1) step (A) A step of contacting the reaction product in a liquid phase with a catalyst in which at least one metal compound selected from the group consisting of an alkali metal compound and an alkaline earth metal compound is supported on a carrier, or step (B2) ( The reaction product of A) is produced in the gas phase by a catalyst in which at least one metal compound selected from the group consisting of an alkali metal compound and an alkaline earth metal compound is supported on a support, and / or porous silica. viewing including the step of contacting,
The carrier is porous silica, and the porous silica is amorphous silica , general formula (3):

(Wherein R ¹ and n are as defined above)
The manufacturing method of the isocyanate compound shown by these.   The method for producing an isocyanate compound according to claim 1, wherein the enzyme in the step (A) is an immobilized enzyme immobilized on a carrier.   The method for producing an isocyanate compound according to claim 1, wherein the immobilized enzyme is inserted in a reaction vessel as a fixed bed.   The manufacturing method of the isocyanate compound of any one of Claims 1-3 which performs reaction of a process (A) in presence of the solvent inert to reaction.   The method for producing an isocyanate compound according to claim 4, wherein the solvent is at least one solvent selected from the group consisting of an aliphatic solvent, an aromatic solvent, and an ether solvent.   The manufacturing method of the isocyanate compound of any one of Claims 1-5 in which the reaction product of a process (A) contains a carbamate compound.   The manufacturing method of the isocyanate compound of any one of Claims 1-6 whose process (B) is a process (B1).   The manufacturing method of the isocyanate compound of Claim 7 whose catalyst in a process (B1) is a calcination body.   The catalyst in the step (B1) is impregnated with a support in at least one aqueous solution selected from the group consisting of alkali metal compounds and alkaline earth metal compounds, and then dried and / or filtered, and the resulting solid is calcined. The manufacturing method of the isocyanate compound of Claim 8 which is a baked body.   The method for producing an isocyanate compound according to claim 9, wherein the aqueous solution of the metal compound is an aqueous solution of at least one compound selected from the group consisting of nitrates and chlorides.   The method for producing an isocyanate compound according to claim 9 or 10, wherein the aqueous solution of the metal compound is an aqueous solution of at least one compound selected from the group consisting of a lithium compound, a calcium compound, and a magnesium compound.   The method for producing an isocyanate compound according to any one of claims 9 to 11, wherein the aqueous solution of the metal compound is an aqueous solution of lithium nitrate and / or calcium nitrate.   The manufacturing method of the isocyanate compound of any one of Claims 1-6 whose process (B) is a process (B2).   The method for producing an isocyanate compound according to claim 13, wherein in the step (B2), a catalyst having at least one metal compound selected from the group consisting of an alkali metal compound and an alkaline earth metal compound supported on a carrier is used.   The manufacturing method of the isocyanate compound of Claim 14 whose said catalyst is a sintered body.   A fired body in which the catalyst is impregnated with a carrier in at least one aqueous solution selected from the group consisting of an alkali metal compound and an alkaline earth metal compound, then dried and / or filtered, and the resulting solid is fired. The method for producing an isocyanate compound according to claim 15.   The method for producing an isocyanate compound according to claim 16, wherein the aqueous solution of the metal compound is an aqueous solution of at least one compound selected from the group consisting of nitrates and chlorides.   The method for producing an isocyanate compound according to claim 16 or 17, wherein the aqueous solution of the metal compound is an aqueous solution of at least one compound selected from the group consisting of a lithium compound, a calcium compound, and a magnesium compound.   The method for producing an isocyanate compound according to any one of claims 16 to 18, wherein the aqueous solution of the metal compound is an aqueous solution of lithium nitrate and / or calcium nitrate.   The method for producing an isocyanate compound according to claim 13, wherein porous silica is used in the step (B2). Method for producing a porous silica, having an average pore diameter 8Nm～300myuemu, claim 2 0 Symbol mounting isocyanate compounds.

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