JP2015151355A - Method for producing compound having ureido group - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing a compound having a ureido group capable of obtaining a compound having a ureido group useful as an intermediate in producing an isocyanate in a short time with a high yield and high purity while suppressing the generation of by-products observed in a conventional production method.SOLUTION: There is provided a method for producing a compound having a ureido group by reacting an organic primary amine with urea, which comprises a reaction step of circulating a solution containing an organic primary amine, urea and an aromatic hydroxy compound through a flow channel in which the area of the thermally conductive surface of the hollow inside is 1 to 100 cm/cmat a temperature of 30°C or more.

Description

  The present invention relates to a method for producing a compound having a ureido group.

（式中、Ｒは有機基を示し、ｎは１以上の整数を示す。） The compound having a ureido group is a compound represented by the following general formula (3), and is useful as an intermediate material for isocyanate used in polyurethane foam, paints, adhesives and the like.

(In the formula, R represents an organic group, and n represents an integer of 1 or more.)

  Isocyanate can be obtained by performing a urethanization reaction and a thermal decomposition reaction using a compound having a ureido group.

  As a method for producing a compound having a ureido group, for example, Patent Document 1 discloses a method for obtaining a compound having a ureido group by using an aromatic hydroxy compound as a solvent in a ureido reaction using an organic primary amine and urea. It is disclosed.

JP 2012-136482 A

  The ureido reaction disclosed in Patent Document 1 is based on a tank reactor. A tank reactor generally has a low thermal conductivity during mass production, and the reaction time including the temperature rising time tends to be long. When the reaction time is long, the possibility that by-products are generated increases. Under the temperature conditions where the organic primary amine and urea react in the ureido reaction, urea and the compound having a ureido group, which is a product, are unstable to heat, and thus react quickly in a short time. Thus, there are few by-products and a compound having the desired ureido group can be obtained with good yield.

（各式中、Ｒは有機基を示す。） Here, the by-product is, for example, a biuret that is a dimer of urea represented by the following formula (4), a triuret that is a urea trimer represented by the following formula (5), or the following formula (6). A cyanuric acid represented by a compound having a urea bond represented by the following formula (7), a compound having a biuret bond represented by the following formula (8), and a biuret group represented by the following formula (9): It is a compound that has.

(In each formula, R represents an organic group.)

  In the tank reactor, ammonia having a low boiling point generated by thermal decomposition of urea is removed from the liquid phase as the reaction system, so the ammonia concentration in the reaction system becomes low, and is expressed by the above formula (4). Biuret and triuret represented by the above formula (5) are by-produced. Further, the compound having a ureido group as a reaction product can exist stably in the presence of urea, but when urea is exhausted, ureido ends are condensed with each other and have a urea bond represented by the above formula (7). A compound, a compound having a biuret bond represented by the above formula (8), and a compound having a biuret group represented by the above formula (9) are by-produced.

  In addition, about the said by-product, in order to demonstrate easily, although the compound which has one functional group (here, an amino group and a ureido group) is described, the compound which has two or more several functional groups A similar by-product may be produced for.

  The compound produced by these side reactions not only lowers the yield of the compound having a ureido group, which is a desired target, but also a process for producing an isocyanate using a compound having the ureido group. The yield of the process of producing urethane, which is a precursor of isocyanate, and the process of producing isocyanate by thermal decomposition of the urethane), and further, by-products and decomposition products derived from by-products, In some cases, the performance of polyurethane foams, paints, adhesives and the like in which the isocyanate is used may be reduced.

  Therefore, the present invention provides a compound having a ureido group, which is a useful compound as an intermediate in the production of isocyanate, in a short time, while suppressing the production of by-products found in conventional production methods, and high yield. And it aims at providing the manufacturing method of the compound which has a ureido group obtained with high purity.

As a result of repeated investigations on the above problems, the present inventors have made the organic primary amine and urea, which are raw materials, in a flow path having an area of a heat conduction surface in the hollow space of 1 to 100 cm ² / cm ^3. The inventors have found that the above-mentioned problems can be solved by the reaction, and have completed the present invention.

(式中、Ｒ^１は炭素数１〜３５の有機基を示し、ａは１〜１０の整数を示す。）
［６］ａは、２である、［５］に記載のウレイド基を有する化合物の製造方法。
［７］有機基は、酸素原子を含む、［５］又は［６］に記載のウレイド基を有する化合物の製造方法。
［８］芳香族ヒドロキシ化合物は、下記一般式（２）で表される化合物である、［１］〜［７］のいずれか１つに記載のウレイド基を有する化合物の製造方法。

(式中、Ａは芳香環を有する炭素数６〜５０の有機基を示し、ｂは１〜３の整数を示す。)
［９］ｂは、１又は２である、［８］に記載のウレイド基を有する化合物の製造方法。
［１０］芳香環は、ベンゼン環、ナフタレン環及びアントラセン環からなる群から選ばれる少なくとも一つ以上の環である、［８］又は［９］に記載のウレイド基を有する化合物の製造方法。
［１１］芳香環の水素原子が、ハロゲン原子、アルキル基、シクロアルキル基、アリール基、アラルキル基、アリールオキシ基及びアラルキルオキシ基からなる群から選ばれる少なくとも１つ以上の基で置換されている、［８］〜［１０］のいずれか１つに記載のウレイド基を有する化合物の製造方法。
［１２］液相でウレイド化反応をさせる［１］〜［１１］のいずれか１つに記載のウレイド基を有する化合物の製造方法。
［１３］有機第１級アミンのアミノ基に対する尿素の化学量論比が１より大きい、［１］〜［１２］のいずれか１つに記載のウレイド基を有する化合物の製造方法。
［１４］反応工程において、流路に流通させる溶液の温度が、１８０〜２２０℃である、［１］〜［１３］のいずれか１つに記載のウレイド基を有する化合物の製造方法。
［１５］反応工程において、流路に流通させる溶液の流量が、０．１〜１０００ｇ／ｍｉｎである、［１］〜［１４］のいずれか１つに記載のウレイド基を有する化合物の製造方法。 That is, the present invention provides the following manufacturing method.
[1] A method for producing a compound having a ureido group by reacting an organic primary amine and urea, wherein a solution containing the organic primary amine, urea and an aromatic hydroxy compound is heated in a hollow space. The manufacturing method of the compound which has a ureido group which has the reaction process distribute | circulated at the temperature of 30 degreeC or more to the flow path whose area of a conductive surface is 1-100 cm < ² > / cm < ³ >.
[2] A separation step of separating the reaction mixture discharged from the flow path into a gas phase portion and a liquid phase portion after the reaction step, and when the reaction mixture flows from the reaction step to the separation step, The method for producing a compound having a ureido group according to [1], which passes through a pressure control mechanism.
[3] The method for producing a compound having a ureido group according to [2], wherein the pressure control mechanism is a pressure holding valve or a check valve.
[4] The method for producing a compound having a ureido group according to any one of [1] to [3], further comprising a cooling step of cooling the reaction mixture discharged from the flow path after the reaction step.
[5] The method for producing a compound having a ureido group according to any one of [1] to [4], wherein the organic primary amine is a compound represented by the following general formula (1).

(In the formula, R ¹ represents an organic group having ¹ to 35 carbon atoms, and a represents an integer of 1 to 10).
[6] The method for producing a compound having a ureido group according to [5], wherein a is 2.
[7] The method for producing a compound having an ureido group according to [5] or [6], wherein the organic group contains an oxygen atom.
[8] The method for producing a compound having a ureido group according to any one of [1] to [7], wherein the aromatic hydroxy compound is a compound represented by the following general formula (2).

(In the formula, A represents an organic group having 6 to 50 carbon atoms having an aromatic ring, and b represents an integer of 1 to 3).
[9] The method for producing a compound having a ureido group according to [8], wherein b is 1 or 2.
[10] The method for producing a compound having a ureido group according to [8] or [9], wherein the aromatic ring is at least one ring selected from the group consisting of a benzene ring, a naphthalene ring and an anthracene ring.
[11] A hydrogen atom of the aromatic ring is substituted with at least one group selected from the group consisting of a halogen atom, an alkyl group, a cycloalkyl group, an aryl group, an aralkyl group, an aryloxy group and an aralkyloxy group. [8] A method for producing a compound having a ureido group according to any one of [8] to [10].
[12] The method for producing a compound having a ureido group according to any one of [1] to [11], wherein a ureido reaction is performed in a liquid phase.
[13] The process for producing a compound having a ureido group according to any one of [1] to [12], wherein the stoichiometric ratio of urea to the amino group of the organic primary amine is greater than 1.
[14] The method for producing a compound having a ureido group according to any one of [1] to [13], wherein the temperature of the solution to be circulated in the flow path is 180 to 220 ° C. in the reaction step.
[15] The method for producing a compound having a ureido group according to any one of [1] to [14], wherein the flow rate of the solution to be circulated in the flow path in the reaction step is 0.1 to 1000 g / min. .

  According to the present invention, a compound having a ureido group, which is a compound useful as an intermediate in the production of isocyanate, can be produced in a short time with high yield while suppressing the production of by-products found in conventional production methods. It is possible to provide a method for producing a compound having a ureido group, which can be obtained with high efficiency and high purity.

  Hereinafter, preferred embodiments of the present invention will be described in detail.

(式中、Ｒ^１は炭素数１〜３５の有機基を示し、ａは１〜１０の整数を示す。） <Raw materials, solutions, and products>
(Organic primary amine)
An organic primary amine is a compound having one or more organic primary amino groups (amino groups having two hydrogen atoms on a nitrogen atom). In the present embodiment, the organic primary amine is a compound represented by the following general formula (1).

(In the formula, R ¹ represents an organic group having ¹ to 35 carbon atoms, and a represents an integer of 1 to 10).

  In the general formula (1), a is preferably an integer of 2 to 10, more preferably 2.

In the general formula (1), R ¹ is preferably an organic group composed of a carbon atom, an oxygen atom and a hydrogen atom, and is an organic group having no active hydrogen. As used herein, “active hydrogen” refers to a hydrogen atom bonded to an oxygen atom, a sulfur atom, a nitrogen atom, or a silicon atom, and a hydrogen atom of a terminal methine group. For example, —OH group, —C (═O) OH group, —C (═O) H group, —SH group, —SO ₃ H group, —SO ₂ H group, —SOH group, —NH ₂ group, — It is a hydrogen atom contained in an atomic group such as NH-group, -SiH group, -C≡CH group.

R ¹ is not particularly limited, and examples thereof include an aliphatic hydrocarbon group having 1 to 20 carbon atoms, an alicyclic hydrocarbon group having 5 to 20 carbon atoms, and an aromatic hydrocarbon having 6 to 20 carbon atoms. Groups and the like. In the general formula (1), the carbon number of ^{R 1} is preferably 1 to 25, more preferably 1 to 13.

Examples of R ¹ include a group in which the number of hydrogen atoms substituted with a number of amino groups is removed at any position in the structure shown below. Specific examples of the structure include methane, ethane, Linear aliphatic hydrocarbons such as propane, butane, pentane, hexane, and octane; unsubstituted alicyclic hydrocarbons such as cyclopentane, cyclohexane, cycloheptane, cyclooctane, and bis (cyclohexyl); methylcyclopentane, ethylcyclo Pentane, methylcyclohexane (each isomer), ethylcyclohexane (each isomer), propylcyclohexane (each isomer), butylcyclohexane (each isomer), pentylcyclohexane (each isomer), hexylcyclohexane (each isomer), etc. Monoalkyl substituted alicyclic hydrocarbons; dimethylcyclohexane (each isomer), di Dialkyl-substituted alicyclic hydrocarbons such as ethylcyclohexane (each isomer) and dibutylcyclohexane (each isomer); 1,5,5-trimethylcyclohexane, 1,5,5-triethylcyclohexane, 1,5,5 -Trialkyl-substituted alicyclic hydrocarbons such as tripropylcyclohexane (each isomer) and 1,5,5-tributylcyclohexane (each isomer); unsubstituted aromatic hydrocarbons such as benzene and naphthalene; toluene And monoalkyl-substituted aromatic hydrocarbons such as ethylbenzene and propylbenzene; dialkyl-substituted aromatic hydrocarbons such as xylene, diethylbenzene and dipropylbenzene; and aromatic hydrocarbons such as diphenylalkane. Of these, groups derived from hexane, benzene, diphenylmethane, toluene, cyclohexane, xylene, methylcyclohexane, isophorone and dicyclohexylmethane are preferred.

  Examples of organic primary amines include diphenylmethanediamine (each isomer), tolylenediamine (each isomer), hexamethylenediamine, hexadecamethylenediamine, isophoronediamine, naphthalenediamine (each isomer), and tetramethylxylene. Diamine (each isomer), dicyclohexylmethanediamine (each isomer), xylenediamine (each isomer), methylenebis (diisoamyl-phenylene) diamine (each isomer), oxybis (phenylenediamine) (each isomer), thiobis ( Examples thereof include phenylenediamine (each isomer), carbonylbis (phenylene) diamine (each isomer), butenediamine (each isomer), butynylenediamine, hexafluoropropylenediamine (each isomer), and the like.

(urea)
Urea used in the present embodiment is not particularly limited, and industrially available urea can be used. Urea is a compound represented by the following formula (10).

The urea may contain biuret represented by the following formula (4) having a urea bond, triuret represented by the following formula (5), or cyanuric acid represented by the following formula (6). Good. However, generally biuret, triuret and cyanuric acid have low solubility in solvents. When the reaction solution flows through the flow path described later, it is preferable that the reaction solution is a uniform solution in consideration of blockage. Accordingly, urea is preferable in consideration of solubility in an aromatic hydroxy compound described later. The shape of urea is not particularly limited, and for example, it can be used in the form of powder or granule.

（式中、Ａは芳香環を有する炭素数６〜５０の有機基を示し、ｂは１〜３の整数を示す。） (Aromatic hydroxy compound)
The aromatic hydroxy compound refers to a compound having at least one aromatic hydroxy group and an aromatic ring. In the present embodiment, the aromatic hydroxy compound is an aromatic hydroxy compound represented by the following general formula (2).

(In formula, A shows a C6-C50 organic group which has an aromatic ring, b shows the integer of 1-3.)

  In general formula (2), b represents the number of aromatic hydroxy groups and represents an integer of 1 to 3. The aromatic hydroxy group means a hydroxy group bonded to an aromatic ring in the hydroxy group (OH). A means having a ring structure, and A as a whole is an organic group containing a carbon atom having 6 to 50 carbon atoms, and the organic group contains an aromatic ring. A also contains an aromatic ring substituted with b hydroxy groups at any position. The aromatic ring may be monocyclic, polycyclic or heterocyclic, and the hydrogen atom of the ring may be substituted with a group other than the aromatic hydroxy group.

  Examples of other groups include, but are not limited to, halogen atoms, alkyl groups, cycloalkyl groups, aryl groups, aralkyl groups, aryloxy groups, aralkyloxy groups, and the like. In addition, the carbon atom contained in these groups shall be contained in said "C6-C50".

  In General formula (2), carbon number of A becomes like this. Preferably it is 6-33, More preferably, it is 6-24.

  In the general formula (2), the aromatic ring is not particularly limited. For example, a benzene ring, a naphthalene ring, an anthracene ring, a phenanthrene ring, a naphthacene ring, a chrysene ring, a pyrene ring, a triphenylene ring, a pentalene ring, Examples include an azulene ring, a heptalene ring, an indacene ring, a biphenylene ring, an acenaphthylene ring, an aceanthrylene ring, an acephenanthrylene ring, and the like. Among these, a benzene ring and a naphthalene ring are preferable.

  In the general formula (2), from the viewpoint of industrial production, b is preferably 1 or 2, more preferably 1. An aromatic hydroxy compound in which b is 1 generally has a low viscosity.

  Examples of the aromatic hydroxy compound include phenol, methylphenol (each isomer), ethylphenol (each isomer), propylphenol (each isomer), butylphenol (each isomer), pentylphenol (each isomer), Hexylphenol (each isomer), heptylphenol (each isomer), octylphenol (each isomer), nonylphenol (each isomer), decylphenol (each isomer), undecylphenol (each isomer), dodecylphenol ( Each isomer), dimethylphenol (each isomer), diethylphenol (each isomer), dipropylphenol (each isomer) dibutylphenol (each isomer), dipentylphenol (each isomer), dihexylphenol (each isomer) Body), diheptylphenol (each isomer), Diocti Phenol (each isomer), dibutylmethylphenol (each isomer), dimethylmethoxyphenol (each isomer), naphthol (each isomer), phenylphenol (each isomer), phenoxyphenol (each isomer), cumyl Phenol (each isomer), dicumylphenol (each isomer), etc. are mentioned.

(solution)
The solution introduced into the flow path and circulated contains the organic primary amine, urea, and an aromatic hydroxy compound. Here, in the production of a compound having a ureido group, the aromatic hydroxy compound acts as a solvent.

  In order to increase the reaction rate and complete the reaction at an early stage, urea is preferably used in an excess amount relative to the amino group of the organic primary amine. However, if too much urea is used, the reactor becomes large. It is not preferable from the viewpoint of suppressing by-products. Therefore, the amount of urea used is preferably greater than 1 in stoichiometric ratio to the amino group of the organic primary amine, more preferably in the range of 1 to 1000 times, and still more preferably in the range of 1 to 100 times. Especially preferably, it is the range of 1.2 to 30 times.

  The usage-amount of an aromatic hydroxy compound is a stoichiometric ratio with respect to the amino group of an organic primary amine, Preferably it is the range of 1 to 500 times. In order to suppress the side reaction that generates the compounds of the formulas (4) to (7), the aromatic hydroxy compound is preferably used in an excess amount relative to the amino group of the organic primary amine. If too much aromatic hydroxy compound is used, the reactor becomes too large. Accordingly, the amount of the aromatic hydroxy compound used is a stoichiometric ratio with respect to the amino group of the organic primary amine, more preferably in the range of 1 to 100 times, and still more preferably in the range of 1 to 30 times. .

  As a reaction procedure, from the viewpoint of by-product suppression, an addition method is used in which the number of moles of urea in the liquid phase is larger than the number of moles of amino groups constituting the organic primary amine. Is preferred.

  In the reaction of the organic primary amine and urea, the method for adding the organic primary amine, urea, and aromatic hydroxy compound is not particularly limited, and the solution of the aromatic hydroxy compound and urea is not limited. A method of adding an organic primary amine alone or a mixed solution of an aromatic hydroxy compound and an organic primary amine to the flow path may be used, and the flow path of the solution of the aromatic hydroxy compound and the organic primary amine may be used. Alternatively, urea alone or a mixed solution of an aromatic hydroxy compound and urea may be added. Furthermore, the solution which mixed the aromatic hydroxy compound, urea, and the organic primary amine all at once may be sufficient. However, the mixture is preferably a homogeneous solution in consideration of clogging in the flow path.

  In the production method of the present embodiment, it is not necessary to use a catalyst, but a catalyst can also be used from the viewpoint of completing the ureido reaction in a short time, lowering the reaction temperature, and the like. In a general chemical reaction, an aromatic amine is less reactive than an aliphatic amine. Therefore, when an aromatic amine is used as an organic primary amine, a catalyst is used even in the ureido reaction. May be effective. When using a catalyst, for example, an alcoholate of an organometallic compound, inorganic metal compound, alkali metal, or alkaline earth metal containing tin, lead, copper, titanium, etc., and lithium, sodium, potassium, calcium, barium Basic catalysts such as methylate, ethylate and butyrate (each isomer) can be used.

  In the production method of the present embodiment, another reaction solvent may be used in addition to the aromatic hydroxy compound. When used, an appropriate solvent may be used for the purpose of facilitating the reaction operation. Good. Examples of such solvents include alkanes such as hexane (each isomer), heptane (each isomer), octane (each isomer), nonane (each isomer), decane (each isomer), and the like; benzene, Aromatic hydrocarbons and alkyl-substituted aromatic hydrocarbons such as toluene, xylene (each isomer), ethylbenzene, diisopropylbenzene (each isomer), dibutylbenzene (each isomer), naphthalene, etc .; chlorobenzene, dichlorobenzene (each isomer) ), Bromobenzene, dibromobenzene (each isomer), chloronaphthalene, bromonaphthalene, nitrobenzene, nitronaphthalene and other aromatic compounds substituted by halogens or nitro groups; diphenyl, substituted diphenyl, diphenylmethane, terphenyl, anthracene , Dibenzyltoluene (each isomer), etc. Polycyclic hydrocarbon compounds; aliphatic hydrocarbons such as cyclohexane, cyclopentane, cyclooctane and ethylcyclohexane; alicyclic alcohols such as cyclohexanol, cyclopentanol and cyclooctanol; ketones such as methyl ethyl ketone and acetophenone; Examples include esters such as dibutyl phthalate, dihexyl phthalate, dioctyl phthalate, and benzyl butyl phthalate; ethers and thioethers such as diphenyl ether and diphenyl sulfide; and sulfoxides such as dimethyl sulfoxide and diphenyl sulfoxide.

(Compound having a ureido group)
The compound having a ureido group produced by the production method of the present embodiment is a compound having a “ureido group” defined by the Nomenclature rule C-971 defined by IUPAC, and the ureido group is —NHC ( ═O) a group represented by —NH ₂ .

（式中、Ｒ^１は上記一般式（１）において定義した基を示し、ｃは１〜１０の整数を示す。） In the present embodiment, the compound having a ureido group is a compound represented by the following general formula (11).

(In the formula, R ¹ represents a group defined in the general formula (1), and c represents an integer of 1 to 10.)

In the general formula (11), R ¹ is a group derived from an organic primary amine.

  In the general formula (11), c represents an integer of 1 to 10, but is an integer not exceeding a in the organic primary amine used. That is, when c amino groups are converted to ureido groups among the amino groups of organic primary amines, theoretically, ac amino groups are unreacted in a compound having a ureido group. It is thought that it exists as an amino group.

  The compound having a ureido group obtained by the production method of the present embodiment is not particularly limited. For example, diphenylmethane diurea (each isomer), tolylene diurea (each isomer), hexamethylene diurea, hexa Decamethylene diurea, isophorone diurea, naphthalene diurea (each isomer), tetramethylxylene diurea (each isomer), dicyclohexylmethane diurea (each isomer), xylene diurea (each isomer), methylenebis (diisoamyl-phenylene) diurea ( Isomers), oxybis (phenylenediurea) (each isomer), thiobis (phenylenediurea) (each isomer), carbonylbis (phenylene) diurea (each isomer), butenediurea (each isomer), butynylene diurea , Hexafluoropropylene Diurea (including isomers), and the like.

  The compound having a ureido group obtained by the production method of the present embodiment is suitably used for the production of carbamic acid ester (urethane), particularly for the production of carbamic acid ester as a raw material for producing isocyanate, as will be described later. can do.

<Method for producing a compound having a ureido group>
The method for producing a compound having a ureido group according to this embodiment comprises mixing an organic primary amine represented by the general formula (1), urea, and an aromatic hydroxyl compound represented by the general formula (2). The solution prepared in this manner is subjected to a ureido reaction while flowing through a hollow pipe channel.

  The ureido reaction is a reaction that forms a ureido group. In this embodiment, the ureido group is formed from an organic primary amine and urea.

  In the present embodiment, the side reaction is suppressed by allowing the solution to flow through a tubular channel (pipe) having a small inner diameter and reacting in a short time. Although the mechanism that the effect is obtained by performing the reaction in the flow path is not clear, it is expressed by the above formulas (4) to (6) by completing the reaction at a temperature of 30 ° C. or more in a short time. The by-product reaction of urea is suppressed, and the ureido group represented by the above formulas (7) to (9) is suppressed from becoming a by-product having a urea bond and a compound having a urea bond. I guess it is not.

(Supply process)
The manufacturing method of the present embodiment includes a supply step of preparing a solution to be supplied to the flow path and supplying the solution to the flow path. The temperature at the time of supply is preferably in the range of 50 to 150 ° C. for the purpose of suppressing the decomposition rate of urea and the generation of by-products.

  In general, the organic primary amine used in this embodiment is often solid at room temperature (for example, 20 ° C.). In such a case, the organic primary amine is heated to a temperature higher than the melting point of the organic primary amine. It can also be supplied in a liquid state. From the viewpoint of suppressing side reactions such as heat denaturation reaction, it is also preferable to supply the organic primary amine in a liquid state at a relatively low temperature in a mixture with an aromatic hydroxy compound.

  Urea used in the present embodiment is solid at room temperature (for example, 20 ° C.), but can be supplied in a liquid after being heated to the melting point or higher. From the viewpoint of suppressing by-products due to decomposition of urea, it is also preferable to make urea a mixture with an aromatic hydroxy compound and supply it in a liquid state at a relatively low temperature.

  In any of the above embodiments, it is only necessary that the organic primary amine, urea, and aromatic hydroxyl compound are mixed with each other immediately before the entrance of the flow path provided for the reaction step described later. In this embodiment, when transferring the said preparation liquid toward the said inlet, it is preferable that it is a homogeneous solution, and the temperature of piping during transfer becomes like this. Preferably it is the range of 50-150 degreeC.

  The shape and material of the flow path (pipe) in the supply process are not particularly limited, and may be a flow path composed of a metal or resin tube, or a flow path composed of a plurality of flat plates. Good. Moreover, it may consist of a single flow path or may be a combination of a plurality of flow paths. Moreover, about the material, it is good also as the same material as the flow path used in the reaction process mentioned later.

  The supplying step can be performed under atmospheric pressure, reduced pressure, or increased pressure. Moreover, it is usually preferable to carry out in an inert gas atmosphere such as nitrogen, argon or helium.

(Reaction process)
Examples of the method of performing the reaction while circulating the solution containing the reaction raw material in the flow path include a method of performing the reaction using a flow reactor (flow reactor).

  A flow-type reactor (flow reactor) is an apparatus that allows a reagent to be continuously fed into a reactor and a reactant to be continuously taken out.

The thickness of the flow path is determined by the production amount of the compound having a ureido group and the area of the heat conducting surface with respect to the volume of the hollow interior, but the cross-sectional area is preferably 100 μm ^{2 to} 10,000 mm ² , and 0.5 mm ^{2 to} 3000 mm ^2. Is more preferable. In addition, the length of the flow path is preferably 1 cm to 300 m, and more preferably 1 m to 50 m, for the supply step and the reaction step. Moreover, as for the length as a reaction process, 50 cm-40 m are preferable. Here, one flow path can share the front part as a supply process and the rear part as a reaction process. In this case, the part where the solution flowing through the flow path can reach the target temperature can be regarded as the reaction process, and the other part can be regarded as the supply process.

The area of the heat conduction surface in the hollow interior of the flow path is preferably in the range where the solution flowing in the pipe is immediately heated to the heating temperature, and is in the range of 1 to 100 cm ² / cm ³ per volume of the hollow interior. . Preferably it is 10-50 cm < ² > / cm < ³ >.

  Here, the “heat conducting surface” refers to an inner wall surface of a portion of the flow path that is heated from the outside by a heating device or the like. A heating apparatus etc. are not specifically limited, For example, the heating by a heater or steam piping, the heating by high temperature oil piping can be used.

  The pressure applied in the flow path of the heat conduction surface may be equal to or lower than the pressure resistance of the flow path, and is preferably in the range of 0.1 MPa to 10 MPa, more preferably in the range of 0.1 MPa to 1 MPa.

  A known material can be used as the material of the flow path (pipe), and is not particularly limited. For example, glass, stainless steel, carbon steel, hastelloy, a glass-lined base material, Teflon ( (Registered trademark) A coating with a coating can also be used.

  The temperature of the heat conducting surface is a temperature at which the solution flowing through the flow path can reach the target temperature. Therefore, the heating temperature of the flow path is preferably in the range of 30 to 260 ° C, more preferably in the range of 80 to 240 ° C, and in the range of 180 to 220 ° C from the viewpoint of yield improvement, production efficiency improvement, and suppression of by-product formation. Is more preferable.

  The flow rate is determined by the time required for the reaction, that is, the required residence time and the size (thickness, length) of the flow path. For example, 0.1 g / min to 1000 g / min, that is, every minute 0.1 to 1000 g.

  In the flow path, a mixer may be used for mixing the solution. As the mixer, for example, a T-shaped static mixer, a helix mixer, or the like can be used. Of these, the static type is preferable in the region where the flow rate is large (for example, 2 mL / min or more) because pressure is not applied, but in the low flow region (for example, 2 mL / min or less), the helix type is preferable in terms of mixing efficiency. preferable.

  As a material of the mixer, a known material can be used, and is not particularly limited. For example, glass, stainless steel, carbon steel, hastelloy, a glass-lined base material, or Teflon (registered trademark) The coated one can also be used.

  In this embodiment, the reaction time (passage time of the flow path in the reaction step) is preferably in the range of 0.001 to 100 minutes, more preferably in the range of 0.01 to 80 minutes, and still more preferably in the range of 0.1 to 5 The range of minutes. The reaction solution may be collected, and the reaction may be terminated after confirming that a desired amount of a compound having a ureido group has been formed, for example, by liquid chromatography.

  The reaction step can be performed under atmospheric pressure, reduced pressure, or increased pressure. Moreover, it is usually preferable to carry out in an inert gas atmosphere such as nitrogen, argon or helium.

<Separation process>
The separation step is a step of separating the gas phase portion and the liquid phase portion from each other in the reaction mixture discharged from the flow path, and specifically, a step of separating ammonia by-produced in the reaction step. is there. The conditions for the separation are not particularly limited as long as the gas phase and the liquid phase can be present, and may be any of reduced pressure, pressurized pressure and normal pressure, and the temperature is also particularly limited. Absent.

  The apparatus for separation is not limited, and it is sufficient that the gas phase part and the liquid phase part can be separated. For example, after the separation step, when the next reaction step using a compound having a ureido group as a raw material is reserved and the reaction step is performed under reduced pressure conditions, the reaction liquid (liquid phase part) of the previous reaction step is used. ) Is sent to the next step, the gas phase ammonia is quickly separated. The components of the gas phase part and the liquid phase part which are separated from each other are not limited, and the gas phase part component includes urea, isocyanic acid, an aromatic hydroxy compound and the like in addition to ammonia. Also good. Further, for example, the gas phase part and the liquid phase part can be quickly separated by sending the reaction liquid to the decompressed container.

<Pressure control mechanism>
In this embodiment, it is preferable that the pressure control mechanism is passed during the flow from the reaction step to the separation step. Here, the pressure control mechanism refers to a mechanism that maintains the pressure in the flow path of the reaction process and puts it in a pressurized state.

  For example, it is preferable that a device having a mechanism for holding pressure is provided at the outlet of the flow path. The mechanism that maintains the pressure suppresses the generation of a gas phase portion due to the vaporization of ammonia generated by the ureido reaction in the flow path. By maintaining the pressure, gas phase is prevented from occurring in the piping of the flow reactor, and by increasing the solubility of ammonia in the reaction solution, the modification reaction of the compound having a ureido group and the side reaction of the urea component are suppressed. be able to. Examples of the pressure control mechanism include a pressure holding valve or a check valve.

  The purpose of the pressure control mechanism is to suppress by-products and to secure a residence time by suppressing the vaporization of ammonia by-produced by the reaction between the organic primary amine and urea. The type, shape, and material of the pressure holding valve are not particularly limited. For example, a dome load type pressure holding valve and a spring load type pressure holding valve can be used. The pressure to be held is preferably in the range of 0.1 MPa to 1 MPa, and more preferably in the range of 0.1 MPa to 0.5 MPa.

<Cooling process>
It is preferable that the manufacturing method of this embodiment has a cooling process which cools a reaction mixture after a reaction process. As an example of the cooling step, cooling the reaction mixture by an apparatus having a mechanism having a cooling unit can be mentioned. The cooling step may be performed either before or after the pressure control mechanism. Further, the cooling step may be performed before or after the separation step. When carried out after the separation step, the above “reaction mixture” means the liquid phase part.

  The mechanism with a cooling unit aims to prevent the denaturation reaction of the compound having a ureido group produced in the reaction process by rapid cooling, and to increase the solubility of ammonia in the reaction solution and suppress the denaturation reaction of ureas. It is. The kind, shape, and material of the cooling device are not particularly limited. For example, a method of cooling a channel or the like with a liquid, gas, or solid cooled to a cooling temperature can be used.

  The cooling temperature should just be the temperature which is more than melting | fusing point of the aromatic hydroxy compound in a solution, and the component with low solubility in a reaction liquid does not precipitate, Preferably it is the range of 90-120 degree | times.

  The cooling time is a time required for the temperature of the reaction solution flowing through the flow path to fall to the cooling temperature, and is preferably about 0.1 to 5 minutes.

  The cooling step can be performed under atmospheric pressure, reduced pressure, or increased pressure. Moreover, it is usually preferable to carry out in an inert gas atmosphere such as nitrogen, argon or helium.

<Method for producing carbamic acid ester>
In the method for producing a carbamic acid ester using a compound having a ureido group as a raw material, a carbamic acid ester can be produced by reacting a compound having a ureido group with an aromatic hydroxy compound. Since the method for producing a compound having a ureido group according to the present embodiment can obtain a compound having a ureido group in high yield and high purity, a raw material for producing a carbamic acid ester without purifying the compound having a ureido group Can be used as In addition, the compound having a ureido group obtained by the production method of the present embodiment may be used as a raw material for producing a carbamic acid ester after being purified by a known method such as distillation separation, crystallization, or membrane separation. it can.

  When the reaction mixture containing a compound having an ureido group and an aromatic hydroxy compound obtained in the above reaction step is used without purification, the amount of the aromatic hydroxy compound relative to the ureido group of the compound having a ureido group is a desired amount. Adjust so that For example, an aromatic hydroxy compound may be added or distilled and separated so that the amount of the aromatic hydroxy compound is in the range of 1 to 500 times the stoichiometric ratio with respect to the ureido group of the compound having a ureido group to be used. It adjusts by removing an aromatic hydroxy compound by well-known methods, such as.

  As the reactor for producing the carbamic acid ester, it is preferable to use a reactor different from the reactor for carrying out the step of producing a compound having a ureido group. As a result of the study by the present inventors, surprisingly, in the reaction for producing a compound having a ureido group (reaction between an amine and a urea compound), the equilibrium of the reaction is overwhelmingly biased toward the production side. Thus, it was found that the reaction for producing the carbamic acid ester (reaction between a compound having a ureido group and a hydroxy compound) is overwhelmingly biased toward the original system. That is, in the reaction for producing a compound having a ureido group, the reaction proceeds regardless of whether the produced ammonia is removed from the system or not, but the reaction for producing the carbamic acid ester is conducted outside the system. If not removed, the reaction will not proceed. Therefore, the reaction for producing the carbamic acid ester is preferably performed by using a column reactor, a distillation column, a packed column, a thin film distiller, or the like to increase the removal efficiency of by-product ammonia.

  For example, a step of producing a compound having a ureido group is performed in a flow reactor that circulates the flow path as described above, and a reaction liquid obtained in the step is used to produce a carbamate (for example, a reactor (for example, And a method of producing a carbamic acid ester by transferring to a column reactor, a distillation column, a packed column, a thin film distillation device, etc.).

（式中、Ｒ^１は上記式（１）において定義した基を示し、Ａは上記式（２）において定義した有機基を示し、ｂは上記式（２）において定義した整数を示し、ｄは１〜１０の整数であって本化合物の原料である上記式（８）におけるｃを超えない数である。） The carbamic acid ester obtained by the above reaction is a compound represented by the following formula (12).

(Wherein R ¹ represents a group defined in the above formula (1), A represents an organic group defined in the above formula (2), b represents an integer defined in the above formula (2), and d represents (It is an integer of 1 to 10 and is a number not exceeding c in the above formula (8) which is a raw material of the present compound.)

  The carbamic acid ester represented by the above formula (12) is not particularly limited, and examples thereof include N, N′-hexanediyl-bis-carbamic acid diphenyl ester and N, N′-hexanediyl-bis. -Carbamic acid di (methylphenyl) ester (each isomer), N, N'-hexanediyl-bis-carbamic acid di (ethylphenyl) ester (each isomer), N, N'-hexanediyl-bis-carbamine Acid di (propylphenyl) ester (each isomer), N, N'-hexanediyl-bis-carbamic acid di (butylphenyl) ester (each isomer), N, N'-hexanediyl-bis-carbamic acid di (Pentylphenyl) ester (each isomer), N, N′-hexanediyl-bis-carbamic acid di (hexylphenyl) ester ( Isomers), N, N′-hexanediyl-bis-carbamic acid di (heptylphenyl) ester (each isomer), N, N′-hexanediyl-bis-carbamic acid di (octylphenyl) ester (each isomer) ), N, N′-hexanediyl-bis-carbamic acid di (phenylphenyl) ester (each isomer), N, N′-hexanediyl-bis-carbamic acid di (phenoxyphenyl) ester (each isomer), N, N′-hexanediyl-bis-carbamic acid di (cumylphenyl) ester (each isomer), diphenyl-4,4′-methylene-dicyclohexyl carbamate, di (methylphenyl) -4,4′-methylene-dicyclohexyl carbamate Di (ethylphenyl) -4,4′-methylene-dicyclohexyl carbamate, di (pro Ruphenyl) -4,4′-methylene-dicyclohexylcarbamate (each isomer), di (butylphenyl) -4,4′-methylene-dicyclohexylcarbamate (each isomer), di (pentylphenyl) -4,4′- Methylene-dicyclohexyl carbamate (each isomer), di (hexylphenyl) -4,4′-methylene-dicyclohexyl carbamate (each isomer), di (heptylphenyl) -4,4′-methylene-dicyclohexyl carbamate (each isomer) ), Di (octylphenyl) -4,4'-methylene-dicyclohexylcarbamate (each isomer), di (phenylphenyl) -4,4'-methylene-dicyclohexylcarbamate (each isomer), di (phenoxyphenyl)- 4,4'-methylene-dicyclohexyl carbamate ( Each isomer), di (cumylphenyl) -4,4′-methylene-dicyclohexylcarbamate (each isomer), 3- (phenoxycarbonylamino-methyl) -3,5,5-trimethylcyclohexylcarbamic acid phenyl ester, 3- (Methylphenoxycarbonylamino-methyl) -3,5,5-trimethylcyclohexylcarbamic acid (methylphenoxy) ester (each isomer), 3- (ethylphenoxycarbonylamino-methyl) -3,5,5-trimethylcyclohexylcarbamine Acid (ethylphenyl) ester (each isomer), 3- (propylphenoxycarbonylamino-methyl) -3,5,5-trimethylcyclohexylcarbamic acid (propylphenyl) ester (each isomer), 3- (butylphenoxycarbonyl) Amino- Til) -3,5,5-trimethylcyclohexylcarbamic acid (butylphenyl) ester (each isomer), 3- (pentylphenoxycarbonylamino-methyl) -3,5,5-trimethylcyclohexylcarbamic acid (pentylphenyl) ester (Each isomer), 3- (hexylphenoxycarbonylamino-methyl) -3,5,5-trimethylcyclohexylcarbamic acid (hexylphenyl) ester (each isomer), 3- (heptylphenoxycarbonylamino-methyl) -3 , 5,5-Trimethylcyclohexylcarbamic acid (heptylphenyl) ester (each isomer), 3- (octylphenoxycarbonylamino-methyl) -3,5,5-trimethylcyclohexylcarbamic acid (octylphenyl) ester (each isomer) ), -(Octylphenoxycarbonylamino-methyl) -3,5,5-trimethylcyclohexylcarbamic acid (phenylphenyl) ester (each isomer), 3- (octylphenoxycarbonylamino-methyl) -3,5,5-trimethylcyclohexyl Carbamic acid (phenoxyphenyl) ester (each isomer), 3- (octylphenoxycarbonylamino-methyl) -3,5,5-trimethylcyclohexylcarbamic acid (cumylphenyl) ester (each isomer), toluene-dicarbamic acid diphenyl ester (Each isomer), toluene-dicarbamic acid di (methylphenyl) ester (each isomer), toluene-dicarbamic acid di (ethylphenyl) ester (each isomer), toluene-dicarbamic acid di (propylphenyl) ester (Each isomer), toluene-dicarbamic acid di (butylphenyl) ester (each isomer), toluene-dicarbamic acid di (pentylphenyl) ester (each isomer), toluene-dicarbamic acid di (hexylphenyl) ester (each Isomer), toluene-dicarbamic acid di (heptylphenyl) ester (each isomer), toluene-dicarbamic acid di (octylphenyl) ester (each isomer), toluene-dicarbamic acid di (phenylphenyl) ester (each isomer) ), Toluene-dicarbamic acid di (phenoxyphenyl) ester (each isomer), toluene-dicarbamic acid di (cumylphenyl) ester (each isomer), N, N ″-(4,4′-methanediyl-diphenyl)- Biscarbamic acid diphenyl ester, N, N ′-(4,4′- Tandiyl-diphenyl) -biscarbamic acid di (methylphenyl) ester, N, N ″-(4,4 ″ -methanediyl-diphenyl) -biscarbamic acid di (ethylphenyl) ester, N, N ′-(4 , 4′-methanediyl-diphenyl) -biscarbamic acid di (propylphenyl) ester, N, N ′-(4,4′-methanediyl-diphenyl) -biscarbamic acid di (butylphenyl) ester, N, N′- (4,4 ″ -methanediyl-diphenyl) -biscarbamic acid di (pentylphenyl) ester, N, N ′-(4,4′-methanediyl-diphenyl) -biscarbamic acid di (hexylphenyl) ester, N, N ′-(4,4′-methanediyl-diphenyl) -biscarbamic acid di (heptylphenyl) ester, N N ′-(4,4′-methanediyl-diphenyl) -biscarbamic acid di (octylphenyl) ester (each isomer), N, N ″-(4,4′-methanediyl-diphenyl) -biscarbamic acid di (Phenylphenyl) ester (each isomer), N, N ′-(4,4′-methanediyl-diphenyl) -biscarbamic acid di (phenoxyphenyl) ester (each isomer), N, N ′-(4 4'-methanediyl-diphenyl) -biscarbamic acid di (cumylphenyl) ester (each isomer) and the like.

  The carbamic acid ester produced by the method described above can be suitably used as a raw material for producing isocyanate.

  The preferred embodiment of the present invention has been described above, but the present invention is not limited to the above embodiment.

  Hereinafter, the contents of the present invention will be described more specifically with reference to examples and comparative examples. In addition, this invention is not limited to the following Example.

[Analysis method]
(1) Analysis conditions for high performance liquid chromatography Apparatus: LC-10AT (manufactured by Shimadzu Corporation)
Column: Inertsil-ODS / particle diameter 5 μm (manufactured by GL Sciences Inc.)
Column size: 4.6 mm x 150 mm
Column temperature: 40 ° C
Eluent: A solution Acetonitrile, B solution 0.3 wt% phosphoric acid aqueous solution Flow rate: 1.0 mL / min
Detector: UV 210nm
Gradient: Initial A liquid: 5 vol% / B liquid: 95 vol% → 15 minutes later A liquid: 15 vol% / B liquid: 85 vol% → 20 minutes later A liquid: 15 vol% / B liquid: 85 vol% (linear gradient)
(2) Analytical sample of high performance liquid chromatography 100 mg of sample and internal standard; 10 mg of 1,1-diethylurea was dissolved in 1.5 g of acetic acid to prepare an analytical sample.
(3) Quantitative analysis method Each standard substance was analyzed, and based on the prepared calibration curve, quantitative analysis of the analysis sample solution was performed. In addition, unless otherwise indicated, it performed on 25 degreeC conditions.

[Example 1]
A glass four-necked flask (internal volume 200 mL) equipped with a thermometer and a stirrer was charged with 10.1 g of urea (manufactured by Wako Pure Chemical Industries, Ltd.) and 159.2 g of 4-cumylphenol (manufactured by Tokyo Chemical Industry Co., Ltd.). The inside of the flask was purged with nitrogen. Under atmospheric pressure and nitrogen atmosphere, the flask was immersed in a preheated oil bath, and the internal temperature was set to 80 ° C. while stirring the contents to obtain a uniform solution. A mixture of 10.1 g of 1,6-hexamethylenediamine (manufactured by Asahi Kasei Chemicals) and 10.1 g of 4-cumylphenol (urea / amino group of organic primary amine = 1.25 / 1) is heated in advance. After making a uniform solution, the solution was added dropwise from a dropping funnel heated to 50 ° C. to obtain a uniform solution. This solution was fed to a SUS316L 1/8 inch pipe tube (inner diameter 1.18 mm, length 3 m, heat transfer surface area 34 cm ² / cm ³ ) at a rate of 1 g / min using a feed pump, After flowing through the oil bath at a temperature of 180 ° C. for about 3 minutes, the oil bath cooled to a temperature of 90 ° C. was passed through for 1 minute. When the reaction solution obtained from the piping tube was analyzed by high performance liquid chromatography, 1,6-hexamethylene diurea was obtained at a yield of 95% with respect to the charged hexamethylene diamine.

[Example 2]
A glass four-necked flask (internal volume 200 mL) equipped with a thermometer and a stirrer was charged with 10.1 g of urea (manufactured by Wako Pure Chemical Industries, Ltd.) and 159.2 g of 4-cumylphenol (manufactured by Tokyo Chemical Industry Co., Ltd.). The inside of the flask was purged with nitrogen. Under atmospheric pressure and nitrogen atmosphere, the flask was immersed in a preheated oil bath, and the internal temperature was set to 80 ° C. while stirring the contents to obtain a uniform solution. A mixture of 10.1 g of 1,6-hexamethylenediamine (manufactured by Asahi Kasei Chemicals) and 10.1 g of 4-cumylphenol (urea / amino group of organic primary amine = 1.25 / 1) is heated in advance. After making a uniform solution, the solution was added dropwise from a dropping funnel heated to 50 ° C. to obtain a uniform solution. This solution was fed to a SUS316L 1/8 inch pipe tube (inner diameter 1.18 mm, length 3 m, heat transfer surface area 34 cm ² / cm ³ ) at a rate of 1 g / min using a feed pump, After flowing through the oil bath at a temperature of 200 ° C. for about 1.5 minutes, the oil bath cooled to a temperature of 90 ° C. was passed through for 1 minute. When the reaction liquid obtained from the piping tube was analyzed by high performance liquid chromatography, 1,6-hexamethylene diurea was obtained at a yield of 95% with respect to the charged 1,6-hexamethylenediamine.

[Comparative Example 1]
A glass 4-necked flask (300 mL in volume) equipped with a thermometer and a stirrer was charged with 7.5 g of urea (manufactured by Wako Pure Chemical Industries, Ltd.) and 159.2 g of 4-cumylphenol (manufactured by Tokyo Chemical Industry Co., Ltd.). The inside of the flask was purged with nitrogen. Under atmospheric pressure and nitrogen atmosphere, the flask was immersed in a preheated oil bath, and the internal temperature was adjusted to 180 ° C. while stirring the contents to obtain a uniform solution. A mixture of 10.1 g of 1,6-hexamethylenediamine (manufactured by Asahi Kasei Chemicals) and 10.1 g of 4-cumylphenol was heated in advance to form a uniform solution, and then dropped from a dropping funnel heated to 50 ° C. A uniform solution was obtained (the area of the heat conduction surface of the solution was about 0.73 cm ² / cm ³ ). One hour after the completion of the addition, a part of the reaction solution was taken out and analyzed by high performance liquid chromatography. As a result, 1,6-hexamethylenediurea was obtained in a yield of 70% with respect to 1,6-hexamethylenediamine charged. It was.

[Comparative Example 2]
In a glass four-necked flask (internal volume 300 mL) equipped with a thermometer and a stirrer, 10.1 g of 1,6-hexamethylenediamine (manufactured by Asahi Kasei Chemicals) and 4-cumylphenol (manufactured by Tokyo Chemical Industry Co., Ltd.) 159.2 g was charged and the inside of the flask was purged with nitrogen. Under atmospheric pressure and nitrogen atmosphere, the flask was immersed in a preheated oil bath, the contents were stirred and the internal temperature was adjusted to 180 ° C. to obtain a uniform solution (the area of the heat conduction surface of the solution was about 0.73 cm). ² / cm ³ ). 10.1 g of urea (manufactured by Wako Pure Chemical Industries, Ltd.) was added to this homogeneous solution, and after 1 hour, a part of the reaction solution was taken out and analyzed by high performance liquid chromatography. In contrast, 1,6-hexamethylenediurea was obtained in a yield of 75%.

[Example 3]
A glass four-necked flask (internal volume 200 mL) equipped with a thermometer and a stirrer was charged with 10.1 g of urea (manufactured by Wako Pure Chemical Industries, Ltd.) and 159.2 g of 4-cumylphenol (manufactured by Tokyo Chemical Industry Co., Ltd.). The inside of the flask was purged with nitrogen. Under atmospheric pressure and nitrogen atmosphere, the flask was immersed in a preheated oil bath, and the internal temperature was set to 80 ° C. while stirring the contents to obtain a uniform solution. A mixture of 14.7 g of 3-aminomethyl-3,5,5-trimethylcyclohexylamine (manufactured by Asahi Kasei Chemicals) and 10.1 g of 4-cumylphenol was preheated to obtain a homogeneous solution, and then heated to 50 ° C. The solution was dropped from the dropping funnel thus obtained to make a uniform solution. This solution was fed to a SUS316L 1/8 inch pipe tube (inner diameter 1.18 mm, length 3 m, heat transfer surface area 34 cm ² / cm ³ ) at a rate of 1 g / min using a feed pump, After flowing through the oil bath at a temperature of 200 ° C. for about 1.5 minutes, the oil bath cooled to a temperature of 90 ° C. was passed through for 1 minute. When the reaction solution obtained from the piping tube was analyzed by high performance liquid chromatography, 3-aminomethyl-3,5, with a yield of 95% based on the charged 3-aminomethyl-3,5,5-trimethylcyclohexylamine. 5-Trimethylcyclohexylurea was obtained.

[Example 4]
A glass four-necked flask (internal volume 200 mL) equipped with a thermometer and a stirrer was charged with 10.1 g of urea (manufactured by Wako Pure Chemical Industries, Ltd.) and 159.2 g of 4-cumylphenol (manufactured by Tokyo Chemical Industry Co., Ltd.). The inside of the flask was purged with nitrogen. Under atmospheric pressure and nitrogen atmosphere, the flask was immersed in a preheated oil bath, and the internal temperature was set to 80 ° C. while stirring the contents to obtain a uniform solution. A mixture of 10.5 g of 2,4-tolylenediamine (manufactured by Asahi Kasei Chemicals) and 10.1 g of 4-cumylphenol was heated in advance to form a uniform solution, and then dropped from a dropping funnel heated to 50 ° C. A homogeneous solution was obtained. This solution was fed to a SUS316L 1/8 inch pipe tube (inner diameter 1.18 mm, length 3 m, heat transfer surface area 34 cm ² / cm ³ ) at a rate of 1 g / min using a feed pump, After flowing through the oil bath at a temperature of 200 ° C. for about 1.5 minutes, the oil bath cooled to a temperature of 90 ° C. was passed through for 1 minute. When the reaction solution obtained from the piping tube was analyzed by high performance liquid chromatography, 2,4-tolylene diurea was obtained at a yield of 95% with respect to the charged 2,4-tolylenediamine.

[Example 5]
A glass four-necked flask (internal volume 200 mL) equipped with a thermometer and a stirrer was charged with 10.1 g of urea (manufactured by Wako Pure Chemical Industries, Ltd.) and 159.2 g of 4-cumylphenol (manufactured by Tokyo Chemical Industry Co., Ltd.). The inside of the flask was purged with nitrogen. Under atmospheric pressure and nitrogen atmosphere, the flask was immersed in a preheated oil bath, and the internal temperature was set to 80 ° C. while stirring the contents to obtain a uniform solution. A mixture of 17.1 g of 4,4-diphenylmethanediamine (manufactured by Asahi Kasei Chemicals) and 10.1 g of 4-cumylphenol was previously heated to obtain a uniform solution, and then dropped from a dropping funnel heated to 50 ° C. It was set as the solution. This solution was fed to a SUS316L 1/8 inch pipe tube (inner diameter 1.18 mm, length 3 m, heat transfer surface area 34 cm ² / cm ³ ) at a rate of 1 g / min using a feed pump, After flowing through the oil bath at a temperature of 200 ° C. for about 1.5 minutes, the oil bath cooled to a temperature of 90 ° C. was passed through for 1 minute. When the reaction liquid obtained from the piping tube was analyzed by high performance liquid chromatography, 4,4-diphenylmethane diurea was obtained at a yield of 95% with respect to the charged 4,4-diphenylmethanediamine.

[Example 6]
A glass four-necked flask (internal volume 200 mL) equipped with a thermometer and a stirrer was charged with 10.1 g of urea (manufactured by Wako Pure Chemical Industries, Ltd.) and 159.2 g of 4-cumylphenol (manufactured by Tokyo Chemical Industry Co., Ltd.). The inside of the flask was purged with nitrogen. Under atmospheric pressure and nitrogen atmosphere, the flask was immersed in a preheated oil bath, and the internal temperature was set to 80 ° C. while stirring the contents to obtain a uniform solution. A mixture of 18.1 g of dicyclohexylmethane 4,4′-diamine (manufactured by Asahi Kasei Chemicals) and 10.1 g of 4-cumylphenol was heated in advance to form a homogeneous solution, and then added dropwise from a dropping funnel heated to 50 ° C. A homogeneous solution was obtained. This solution was fed to a SUS316L 1/8 inch pipe tube (inner diameter 1.18 mm, length 3 m, heat transfer surface area 34 cm ² / cm ³ ) at a rate of 1 g / min using a feed pump, After flowing through the oil bath at a temperature of 200 ° C. for about 1.5 minutes, the oil bath cooled to a temperature of 90 ° C. was passed through for 1 minute. When the reaction solution obtained from the piping tube was analyzed by high performance liquid chromatography, dicyclohexylmethane 4,4′-diurea was obtained at a yield of 95% with respect to the charged dicyclohexylmethane 4,4′-diamine.

[Example 7]
A glass four-necked flask (internal volume 200 mL) equipped with a thermometer and a stirrer was charged with 10.1 g of urea (manufactured by Wako Pure Chemical Industries, Ltd.) and 71.0 g of phenol (manufactured by Tokyo Chemical Industry Co., Ltd.). Was replaced with nitrogen. Under atmospheric pressure and nitrogen atmosphere, the flask was immersed in a preheated oil bath, and the internal temperature was set to 80 ° C. while stirring the contents to obtain a uniform solution. A mixture of 10.1 g of 1,6-hexamethylenediamine (manufactured by Asahi Kasei Chemicals) and 10.1 g of 4-cumylphenol was heated in advance to form a uniform solution, and then dropped from a dropping funnel heated to 50 ° C. A homogeneous solution was obtained. This solution was fed to a SUS316L 1/8 inch pipe tube (inner diameter 1.18 mm, length 3 m, heat transfer surface area 34 cm ² / cm ³ ) at a rate of 1 g / min using a feed pump, After flowing through the oil bath at a temperature of 180 ° C. for about 3 minutes, the oil bath cooled to a temperature of 90 ° C. was passed through for 1 minute. When the reaction liquid obtained from the piping tube was analyzed by high performance liquid chromatography, 1,6-hexamethylene diurea was obtained at a yield of 95% with respect to the charged 1,6-hexamethylenediamine.

[Example 8]
To a glass four-necked flask (internal volume 200 mL) equipped with a thermometer and a stirrer, 10.1 g of urea (manufactured by Wako Pure Chemical Industries, Ltd.), 2,4-di-tert-amylphenol (manufactured by Tokyo Chemical Industry Co., Ltd.) 176.8 g was charged and the inside of the flask was purged with nitrogen. Under atmospheric pressure and nitrogen atmosphere, the flask was immersed in a preheated oil bath, and the internal temperature was set to 80 ° C. while stirring the contents to obtain a uniform solution. A mixture of 10.1 g of 1,6-hexamethylenediamine (manufactured by Asahi Kasei Chemicals) and 10.1 g of 2,4-di-tert-amylphenol was heated in advance to a uniform solution, and then dropped at 50 ° C. It was dripped from the funnel to make a uniform solution. This solution was fed to a SUS316L 1/8 inch pipe tube (inner diameter 1.18 mm, length 3 m, heat transfer surface area 34 cm ² / cm ³ ) at a rate of 1 g / min using a feed pump, After flowing through the oil bath at a temperature of 200 ° C. for about 1.5 minutes, the oil bath cooled to a temperature of 90 ° C. was passed through for 1 minute. When the reaction liquid obtained from the piping tube was analyzed by high performance liquid chromatography, 1,6-hexamethylene diurea was obtained at a yield of 95% with respect to the charged 1,6-hexamethylenediamine.

[Example 9]
A glass four-necked flask (internal volume: 200 mL) equipped with a thermometer and a stirrer is charged with 10.1 g of urea (manufactured by Wako Pure Chemical Industries, Ltd.) and 155.6 g of 4-tert-octylphenol (manufactured by Tokyo Chemical Industry Co., Ltd.). The inside of the flask was purged with nitrogen. Under atmospheric pressure and nitrogen atmosphere, the flask was immersed in a preheated oil bath, and the internal temperature was set to 80 ° C. while stirring the contents to obtain a uniform solution. A mixture of 10.1 g of 1,6-hexamethylenediamine (manufactured by Asahi Kasei Chemicals) and 10.1 g of 4-tert-octylphenol was heated in advance to make a uniform solution, and then dropped from a dropping funnel heated to 50 ° C. A homogeneous solution was obtained. This solution was fed to a SUS316L 1/8 inch pipe tube (inner diameter 1.18 mm, length 3 m, heat transfer surface area 34 cm ² / cm ³ ) at a rate of 1 g / min using a feed pump, After flowing through the oil bath at a temperature of 200 ° C. for about 1.5 minutes, the oil bath cooled to a temperature of 90 ° C. was passed through for 1 minute. When the reaction liquid obtained from the piping tube was analyzed by high performance liquid chromatography, 1,6-hexamethylene diurea was obtained at a yield of 95% with respect to the charged 1,6-hexamethylenediamine.

[Example 10]
A glass 4-necked flask (internal volume 200 mL) equipped with a thermometer and a stirrer was charged with 10.1 g of urea (manufactured by Wako Pure Chemical Industries, Ltd.) and 226.6 g of 2-tert-butylphenol (manufactured by Tokyo Chemical Industry Co., Ltd.). The inside of the flask was purged with nitrogen. Under atmospheric pressure and nitrogen atmosphere, the flask was immersed in a preheated oil bath, and the internal temperature was set to 80 ° C. while stirring the contents to obtain a uniform solution. A mixture of 10.1 g of 1,6-hexamethylenediamine (manufactured by Asahi Kasei Chemicals) and 10.1 g of 2-tert-butylphenol was heated in advance to form a uniform solution, and then dropped from a dropping funnel heated to 50 ° C. A homogeneous solution was obtained. This solution was fed to a SUS316L 1/8 inch pipe tube (inner diameter 1.18 mm, length 3 m, heat transfer surface area 34 cm ² / cm ³ ) at a rate of 1 g / min using a feed pump, After flowing through the oil bath at a temperature of 200 ° C. for about 1.5 minutes, the oil bath cooled to a temperature of 90 ° C. was passed through for 1 minute. When the reaction liquid obtained from the piping tube was analyzed by high performance liquid chromatography, 1,6-hexamethylene diurea was obtained at a yield of 95% with respect to the charged 1,6-hexamethylenediamine.

[Example 11]
A glass 4-necked flask (internal volume 200 mL) equipped with a thermometer and a stirrer was charged with 10.1 g of urea (manufactured by Wako Pure Chemical Industries, Ltd.) and 205.4 g of 2-isopropylphenol (manufactured by Tokyo Chemical Industry Co., Ltd.), The flask was purged with nitrogen. Under atmospheric pressure and nitrogen atmosphere, the flask was immersed in a preheated oil bath, and the internal temperature was set to 80 ° C. while stirring the contents to obtain a uniform solution. A mixture of 10.1 g of 1,6-hexamethylenediamine (manufactured by Asahi Kasei Chemicals) and 10.1 g of 2-isopropylphenol was heated in advance to form a uniform solution, and then added dropwise from a dropping funnel heated to 50 ° C. It was set as the solution. This solution was fed to a SUS316L 1/8 inch pipe tube (inner diameter 1.18 mm, length 3 m, heat transfer surface area 34 cm ² / cm ³ ) at a rate of 1 g / min using a feed pump, After flowing through the oil bath at a temperature of 200 ° C. for about 1.5 minutes, the oil bath cooled to a temperature of 90 ° C. was passed through for 1 minute. When the reaction liquid obtained from the piping tube was analyzed by high performance liquid chromatography, 1,6-hexamethylene diurea was obtained at a yield of 95% with respect to the charged 1,6-hexamethylenediamine.

[Example 12]
A glass four-necked flask (200 mL internal volume) equipped with a thermometer and a stirrer was charged with 10.1 g of urea (manufactured by Wako Pure Chemical Industries, Ltd.) and 92.2 g of 2,6-xylenol (manufactured by Tokyo Chemical Industry Co., Ltd.). The inside of the flask was purged with nitrogen. Under atmospheric pressure and nitrogen atmosphere, the flask was immersed in a preheated oil bath, and the internal temperature was set to 80 ° C. while stirring the contents to obtain a uniform solution. A mixture of 10.1 g of 1,6-hexamethylenediamine (manufactured by Asahi Kasei Chemicals) and 10.1 g of 2,6-xylenol was heated in advance to make a uniform solution, and then dropped from a dropping funnel heated to 50 ° C. A homogeneous solution was obtained. This solution was fed to a SUS316L 1/8 inch pipe tube (inner diameter 1.18 mm, length 3 m, heat transfer surface area 34 cm ² / cm ³ ) at a rate of 1 g / min using a feed pump, After flowing through the oil bath at a temperature of 200 ° C. for about 1.5 minutes, the oil bath cooled to a temperature of 90 ° C. was passed through for 1 minute. When the reaction liquid obtained from the piping tube was analyzed by high performance liquid chromatography, 1,6-hexamethylene diurea was obtained at a yield of 95% with respect to the charged 1,6-hexamethylenediamine.

[Example 13]
A glass four-necked flask (internal volume 200 mL) equipped with a thermometer and a stirrer was charged with 10.1 g of urea (manufactured by Wako Pure Chemical Industries, Ltd.) and 332.3 g of 4-nonylphenol (manufactured by Tokyo Chemical Industry Co., Ltd.), The inside of the flask was replaced with nitrogen. Under atmospheric pressure and nitrogen atmosphere, the flask was immersed in a preheated oil bath, and the internal temperature was set to 80 ° C. while stirring the contents to obtain a uniform solution. A mixture of 10.1 g of 1,6-hexamethylenediamine (manufactured by Asahi Kasei Chemicals) and 10.1 g of 4-nonylphenol is heated in advance to obtain a uniform solution, and then added dropwise from a dropping funnel heated to 50 ° C. It was. This solution was fed to a SUS316L 1/8 inch pipe tube (inner diameter 1.18 mm, length 3 m, heat transfer surface area 34 cm ² / cm ³ ) at a rate of 1 g / min using a feed pump, After flowing through the oil bath at a temperature of 200 ° C. for about 1.5 minutes, the oil bath cooled to a temperature of 90 ° C. was passed through for 1 minute. When the reaction liquid obtained from the piping tube was analyzed by high performance liquid chromatography, 1,6-hexamethylene diurea was obtained at a yield of 95% with respect to the charged 1,6-hexamethylenediamine.

[Example 14]
To a glass four-necked flask (internal volume 200 mL) equipped with a thermometer and a stirrer, 10.1 g of urea (manufactured by Wako Pure Chemical Industries, Ltd.) and 247.8 g of 2-tert-amylphenol (manufactured by Tokyo Chemical Industry Co., Ltd.) The flask was purged with nitrogen. Under atmospheric pressure and nitrogen atmosphere, the flask was immersed in a preheated oil bath, and the internal temperature was set to 80 ° C. while stirring the contents to obtain a uniform solution. A mixture of 10.1 g of 1,6-hexamethylenediamine (manufactured by Asahi Kasei Chemicals) and 10.1 g of 2-tert-amylphenol was heated in advance to form a uniform solution, and then dropped from a dropping funnel heated to 50 ° C. A homogeneous solution was obtained. This solution was fed to a SUS316L 1/8 inch pipe tube (inner diameter 1.18 mm, length 3 m, heat transfer surface area 34 cm ² / cm ³ ) at a rate of 1 g / min using a feed pump, After flowing through the oil bath at a temperature of 200 ° C. for about 1.5 minutes, the oil bath cooled to a temperature of 90 ° C. was passed through for 1 minute. When the reaction liquid obtained from the piping tube was analyzed by high performance liquid chromatography, 1,6-hexamethylene diurea was obtained at a yield of 95% with respect to the charged 1,6-hexamethylenediamine.

[Example 15]
To a glass 4-necked flask (internal volume 200 mL) equipped with a thermometer and a stirrer, 10.1 g of urea (manufactured by Wako Pure Chemical Industries, Ltd.) and 268.9 g of 2,6-diisopropylphenol (manufactured by Tokyo Chemical Industry Co., Ltd.) The flask was purged with nitrogen. Under atmospheric pressure and nitrogen atmosphere, the flask was immersed in a preheated oil bath, and the internal temperature was set to 80 ° C. while stirring the contents to obtain a uniform solution. A mixture of 10.1 g of 1,6-hexamethylenediamine (manufactured by Asahi Kasei Chemicals) and 10.1 g of 2,6-diisopropylphenol was heated in advance to form a uniform solution, and then dropped from a dropping funnel heated to 50 ° C. A homogeneous solution was obtained. This solution was fed to a SUS316L 1/8 inch pipe tube (inner diameter 1.18 mm, length 3 m, heat transfer surface area 34 cm ² / cm ³ ) at a rate of 1 g / min using a feed pump, After flowing through the oil bath at a temperature of 200 ° C. for about 1.5 minutes, the oil bath cooled to a temperature of 90 ° C. was passed through for 1 minute. When the reaction liquid obtained from the piping tube was analyzed by high performance liquid chromatography, 1,6-hexamethylene diurea was obtained at a yield of 95% with respect to the charged 1,6-hexamethylenediamine.

  According to the production method of the present invention, a compound having a ureido group, which is a useful compound as an intermediate in producing isocyanate, can be produced in a short time while suppressing the production of by-products found in conventional production methods. Can be obtained with high yield and high purity. Therefore, the production method of the present invention is very useful industrially and has high commercial value.

Claims (15)

A method for producing a compound having a ureido group by reacting an organic primary amine and urea,
Reaction in which a solution containing the organic primary amine, the urea, and the aromatic hydroxy compound is circulated at a temperature of 30 ° C. or higher through a channel having a heat conduction surface area in the hollow of 1 to 100 cm ² / cm ^3. The manufacturing method of the compound which has a process and has a ureido group. A separation step of separating the reaction mixture discharged from the flow path into a gas phase portion and a liquid phase portion after the reaction step;
The method for producing a compound having a ureido group according to claim 1, wherein the reaction mixture passes through a pressure control mechanism when the reaction mixture flows from the reaction step to the separation step.   The method for producing a compound having a ureido group according to claim 2, wherein the pressure control mechanism is a pressure holding valve or a check valve.   The manufacturing method of the compound which has a ureido group of any one of Claims 1-3 which has a cooling process which cools the reaction mixture discharged | emitted from the said flow path after the said reaction process. The said organic primary amine is a manufacturing method of the compound which has a ureido group of any one of Claims 1-4 which is a compound represented by following General formula (1).

(In the formula, R ¹ represents an organic group having ¹ to 35 carbon atoms, and a represents an integer of 1 to 10).   The method for producing a compound having a ureido group according to claim 5, wherein a is 2.   The method for producing a compound having a ureido group according to claim 5 or 6, wherein the organic group contains an oxygen atom. The said aromatic hydroxy compound is a manufacturing method of the compound which has a ureido group of any one of Claims 1-7 which is a compound represented by following General formula (2).

(In formula, A shows a C6-C50 organic group which has an aromatic ring, b shows the integer of 1-3.)   The method for producing a compound having a ureido group according to claim 8, wherein b is 1 or 2.   The method for producing a compound having a ureido group according to claim 8 or 9, wherein the aromatic ring is at least one ring selected from the group consisting of a benzene ring, a naphthalene ring and an anthracene ring.   The hydrogen atom of the aromatic ring is substituted with at least one group selected from the group consisting of a halogen atom, an alkyl group, a cycloalkyl group, an aryl group, an aralkyl group, an aryloxy group and an aralkyloxy group. Item 11. A method for producing a compound having a ureido group according to any one of Items 8 to 10.   The method for producing a compound having a ureido group according to any one of claims 1 to 11, wherein the ureido reaction is carried out in a liquid phase.   The method for producing a compound having a ureido group according to any one of claims 1 to 12, wherein a stoichiometric ratio of the urea to an amino group of the organic primary amine is larger than 1.   The method for producing a compound having a ureido group according to any one of claims 1 to 13, wherein in the reaction step, the temperature of the solution to be circulated through the flow path is 180 to 220 ° C.   The method for producing a compound having a ureido group according to any one of claims 1 to 14, wherein in the reaction step, a flow rate of the solution to be circulated through the flow path is 0.1 to 1000 g / min.