Method for producing urea compound

Abstract

To provide an efficient production method for urea compounds based on carbon dioxide activation using organic catalysts.SOLUTION: A method for producing a urea compound includes reacting an amine compound with carbon dioxide in the presence of an organic catalyst. The organic catalyst contains at least one phosphorus organic catalyst selected from the group consisting of esters of phosphorus oxoacids and phosphine oxides. The ratio of the organic catalyst to 100 mol of the amino groups in the amine compound is more than 0 mol and less than 100 mol.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a method for producing a urea compound. [Background technology]

[0002] Carbon dioxide, known as one of the greenhouse gases, is abundant on Earth and is a valuable resource because it is cheap, has low toxicity, and is non-flammable. Furthermore, if carbon dioxide can be used as a carbon source, it is expected to be effective in reducing the waste of petroleum resources. Therefore, in recent years, there has been a lot of attention on the development of methods to synthesize high-value-added organic compounds using carbon dioxide as a renewable carbon source.

[0003] Urea compounds are useful compounds that are widely used as raw materials for herbicides, pesticides, medicines, and resins. In the conventional industrial synthesis of urea compounds, reagents such as phosgene and carbon monoxide as reactants, and carbonyldiimidazole as condensation agents have been used (Scheme 1(a)). However, phosgene and carbon monoxide are highly toxic, and condensation agents such as carbonyldiimidazole are expensive, so alternative carbon sources have been sought. Therefore, a method for synthesizing urea compounds using amines and carbon dioxide as raw materials has attracted attention (Scheme 1(b)). This method is expected to synthesize urea compounds without using toxic or expensive reagents as carbon sources, and various metal catalysts have been designed to date. However, this method has the problem that the reaction requires high temperature and pressure. In addition, many of the metals that have been used as catalysts are rare and expensive, and are unstable in oxygen and water, making them difficult to handle in air.

[0004] [ka]

[0005] In today's world where environmental issues are a concern, catalysts that take into account the perspective of "green chemistry" are required, and the development of catalysts to replace metal catalysts, which are environmentally hazardous and require careful handling, is being considered. Organocatalysts are one of the catalysts that are expected to play a key role in environmental harmony and element strategies. The synthesis of urea compounds based on carbon dioxide activation using organocatalysts is also being considered. However, organocatalysts generally have disadvantages such as long reaction times and the need for large amounts of catalyst.

[0006] Non-Patent Document 1 reports the synthesis of diphenylurea by reacting carbon dioxide and aniline using diazabicycloundecene (DBU) and sulfur trioxide-trimethylamine complex (Scheme 2). However, this reaction uses a stoichiometric amount of DBU, which is a strong base, and a stoichiometric or greater amount of sulfur trioxide-trimethylamine complex. In other words, 100 moles or more of DBU is used per 100 moles of amino groups in the substrate, and 500 moles or more of sulfur trioxide-trimethylamine complex is used per 100 moles of amino groups in the substrate. In addition, the reaction has a problem of a narrow substrate adaptability range.

[0007] [ka]

[0008] Non-Patent Document 2 reports that 1,3-diphenylurea was synthesized in 85% yield by reacting diphenyl phosphite (HP(=O)(OPh)2) with carbon dioxide at normal pressure and aniline in pyridine solvent (Scheme 3). However, this method uses a stoichiometric amount of diphenyl phosphite. In addition, there is a problem that the substrate adaptability range is narrow.

[0009] [ka]

[0010] Non-Patent Document 3 reports that cyclohexylamine (Cy-NH2) and carbon dioxide were reacted in dichloromethane in the presence of triphenylphosphine (PPh3), carbon tetrachloride (CCl4), and triethylamine (Et3N) to synthesize the corresponding urea compound in high yield (Scheme 4). However, this method uses a stoichiometric amount of triphenylphosphine. In addition, there are problems such as the toxicity of carbon tetrachloride used as an activator and a narrow substrate applicability range.

[0011] [ka]

[0012] Non-Patent Document 4 reports the synthesis of urea compounds using the Mitsunobu reaction (Scheme 5). This method has the advantages that the reaction proceeds under mild reaction conditions, has a wide range of substrate adaptability, and produces the desired urea compounds in high yields. However, it uses a stoichiometric amount of triphenylphosphine.

[0013] [ka] [Prior art documents] [Non-patent literature]

[0014] [Non-Patent Document 1] Synth. Commun., 1995, 25, 2467-2474. [Non-Patent Document 2] Tetrahedron Lett., 1974, 13, 1191-1194. [Non-Patent Document 3] Tetrahedron Lett., 2004, 45, 5027-5029. [Non-Patent Document 4] Monatsh. Chem., 2008, 139, 267-270. Summary of the Invention [Problem to be solved by the invention]

[0015] As described above, efficient synthesis of urea compounds based on carbon dioxide activation using an organic catalyst has not been achieved. The present invention has been made in consideration of the above circumstances, and an object of the present invention is to provide an efficient method for producing a urea compound based on carbon dioxide activation using an organic catalyst. [Means for solving the problem]

[0016] The present invention has the following aspects. [1] A method for producing a urea compound, comprising reacting an amine compound with carbon dioxide in the presence of an organic catalyst, the organic catalyst comprises at least one phosphorus organic catalyst selected from the group consisting of phosphorus oxoacid esters and phosphine oxides; The method for producing a urea compound, wherein a ratio of the organic catalyst to 100 moles of amino groups of the amine compound is more than 0 mole and less than 100 moles. [2] The method for producing a urea compound according to [1], wherein the amine compound is at least one selected from the group consisting of primary amines, secondary amines, disilylamines and monosilylamines. [3] The method for producing a urea compound according to [1] or [2], wherein the amine compound is at least one selected from the group consisting of compounds represented by the following formula (1) and compounds represented by the following formula (2): R 1 -NH-R 2 (1) R 3 -NR 4 -SiR 5 R 6 R 7 (2) However, R 1 represents a substituted or unsubstituted monovalent hydrocarbon group, R 2 represents a hydrogen atom or a substituted or unsubstituted monovalent hydrocarbon group, R 3represents a substituted or unsubstituted monovalent hydrocarbon group, R 4 is SiR 5 R 6 R 7 or a substituted or unsubstituted monovalent hydrocarbon group, R 5 , R 6 and R 7 each independently represents an alkyl group. [4] The method for producing a urea compound according to any one of [1] to [3], wherein the ratio of the organic catalyst to 100 moles of the amino groups is 10 to 30 moles. [5] The method for producing a urea compound according to any one of [1] to [4], wherein the pressure when the amine compound and the carbon dioxide are reacted is normal pressure. [6] The method for producing a urea compound according to any one of [1] to [5], wherein the temperature during the reaction between the amine compound and the carbon dioxide is 80 to 140°C. [7] The method for producing a urea compound according to any one of [1] to [6], comprising reacting the amine compound with the carbon dioxide in the presence of the organic catalyst and an additive. [8] The method for producing a urea compound according to any one of [1] to [7], comprising reacting the amine compound with the carbon dioxide in the presence of the organic catalyst and a polar solvent. [9] The method for producing a urea compound according to [8], further comprising: preparing a mixed solution containing the amine compound, the organic catalyst, and the polar solvent; and bringing the mixed solution into gas-liquid contact with a carbon dioxide-containing gas, thereby reacting the amine compound with the carbon dioxide.

[10] The method for producing a urea compound according to [9], wherein the mixed liquid further contains an additive.

[11] The method for producing a urea compound according to [7] or

[10] , wherein the additive comprises at least one selected from the group consisting of potassium carbonate, a silylating agent, a hydrosilane, and a phenol compound.

[12] The amine compound includes at least one selected from the group consisting of disilylamine and monosilylamine; The method for producing a urea compound according to any one of [7],

[10] and

[11] , wherein the additive contains a phenol compound.

[13] The amine compound includes at least one selected from the group consisting of primary amines and secondary amines; The method for producing a urea compound according to any one of [7] and

[10] to

[12] , wherein the additive comprises at least one selected from the group consisting of potassium carbonate, a silylating agent, and a hydrosilane. Effect of the Invention

[0017] According to the present invention, it is possible to provide an efficient method for producing a urea compound based on carbon dioxide activation using an organic catalyst. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0018] Hereinafter, an embodiment of the present invention will be described. However, this embodiment is specifically described to better understand the gist of the invention, and does not limit the present invention unless otherwise specified. Various modifications of this embodiment are possible as long as they do not change the gist of the present invention. In addition, the symbol "~" indicating a range of numerical values ​​means that the numerical values ​​before and after it are included as the lower limit and upper limit.

[0019] In the method for producing a urea compound of the present invention, an amine compound is reacted with carbon dioxide in the presence of an organic catalyst, thereby producing a urea compound corresponding to the amine compound. The amine compound may be reacted with carbon dioxide in the presence of an organic catalyst and an additive. The amine compound may be reacted with carbon dioxide in the presence of an organic catalyst and a solvent. The amine compound may be reacted with carbon dioxide in the presence of an organic catalyst, an additive and a solvent.

[0020] (Organic catalyst) The organic catalyst includes at least one phosphorus organic catalyst (hereinafter also referred to as "phosphorus organic catalyst A") selected from the group consisting of phosphorus oxoacid esters and phosphine oxides. Examples of phosphorus oxoacids include phosphoric acid, phosphorous acid, phosphonic acid, and phosphinic acid. One of the hydrogen atoms bonded to the phosphorus atom of the phosphinic acid may be substituted with a substituent such as a phenyl group. Examples of esters of these oxoacids include aryl esters, alkyl esters, and fluoroalkyl esters. Examples of the aryl group in the aryl ester include a phenyl group (hereinafter also referred to as "Ph"). The alkyl group in the alkyl ester may be linear or branched, but linear is preferred in that the steric congestion near the phosphorus atom is relatively small. The number of carbon atoms in the alkyl group is, for example, 1 to 4. The fluoroalkyl group in the fluoroalkyl ester may be one in which all of the hydrogen atoms in the alkyl group are substituted with fluorine atoms, or one in which some of the hydrogen atoms in the alkyl group are substituted with fluorine atoms. The fluoroalkyl group may be linear or branched, but linear is preferred in that the steric congestion near the phosphorus atom is relatively small. The number of carbon atoms in the fluoroalkyl group is, for example, 1 to 2. When one of the hydrogen atoms bonded to the phosphorus atom of the phosphinic acid is substituted with a substituent, the organic group that forms an ester (such as an aryl group, an alkyl group, a fluoroalkyl group, etc.) and the substituent may be bonded to each other to form a ring together with the phosphorus atom and the oxygen atom to which they are bonded.

[0021] Specific examples of phosphorus organic catalyst A include phosphonates such as dialkyl phosphonates HP(=O)(O(CH2)3CH3)2, HP(=O)(OCH2CF3)2, and HP(=O)(OCH2CH3)2, diaryl phosphonates HP(=O)(OPh)2, and diaryl aryl phosphonates PhP(=O)(OPh)2, and phosphonate esters such as P(OPh)3, P(O i phosphites such as 9,10-dihydro-9-oxa-10-phosphaphenanthrene 10-oxide (DOPO); and phosphine oxides such as HP(=O)Ph2 and P(=O)Ph3. i Pr represents an isopropyl group.

[0022] As the phosphorus organic catalyst A, from the viewpoint of excellent catalytic activity, an ester of phosphorus oxo acid is preferable, a phosphonic acid diester, a phosphite triester, and a phosphinic acid ester are more preferable, and HP(=O)(OR)2, P(OR)3, and 9,10-dihydro-9-oxa-10-phosphaphenanthrene 10-oxide are more preferable. R represents an aryl group, an alkyl group, or a fluoroalkyl group. The aryl group, the alkyl group, and the fluoroalkyl group are the same as the aryl group in the aryl ester, the alkyl group in the alkyl ester, and the fluoroalkyl group in the fluoroalkyl ester described above. The two R in HP(=O)(OR)2 and the three R in P(OR)3 may be the same or different. As R, from the viewpoint of excellent catalytic activity, an aryl group is preferable, and Ph is particularly preferable.

[0023] The phosphorus organic catalyst A may be used alone or in combination of two or more kinds. The organic catalyst may further include an organic catalyst other than the phosphorus organic catalyst A. The content of the phosphorus organic catalyst A in the organic catalyst is preferably 30 mol % or more, more preferably 50 mol % or more, and particularly preferably 100 mol %, based on 100 mol % of the organic catalyst.

[0024] The amount of the organic catalyst used is more than 0 mole and less than 100 moles, preferably 10 to 30 moles, and more preferably 25 to 30 moles, as a ratio of the organic catalyst to 100 moles of amino groups of the amine compound. If it is equal to or less than the upper limit of the range, it is possible to efficiently produce the urea compound by reducing costs and waste. On the other hand, the higher the amount of the organic catalyst used within the range, the easier the reaction proceeds and the higher the yield of the urea compound tends to be.

[0025] In the past, when producing a urea compound by reacting an amine compound with carbon dioxide in the presence of an organic catalyst, it was thought that the organic catalyst had to be used in a stoichiometric amount or more, that is, in a ratio of 100 moles or more per 100 moles of amino groups in the amine compound. This was because the catalyst would not regenerate. High pressure was also required. According to the investigations of the present inventors, the phosphorus organic catalyst A has an excellent carbon dioxide activation effect, and the reaction proceeds even in an amount less than the stoichiometric amount and without high pressure, making it possible to obtain a urea compound in a sufficient yield.

[0026] (Amine compounds) Examples of the amine compound include primary amines, secondary amines, disilylamines, and monosilylamines. These amine compounds may be used alone or in combination of two or more.

[0027] An example of the primary amine or secondary amine is a compound represented by the following formula (1) (hereinafter also referred to as "compound (1)"). R 1 -NH-R 2 (1) However, R 1 represents a substituted or unsubstituted monovalent hydrocarbon group, R 2 represents a hydrogen atom or a substituted or unsubstituted monovalent hydrocarbon group. When the amine compound is compound (1), R 1 -N(R 2 )-C(=O)-N(R 2 )-R 1 By using two or more compounds (1) in combination, the two R 1 , two R 2 It is also possible to obtain urea compounds each having a different structure.

[0028] R 1 Examples of the monovalent hydrocarbon group in include an alkyl group, a cycloalkyl group, and an aryl group. The alkyl group may be linear or branched. The number of carbon atoms in the alkyl group is, for example, 1 to 12, and further 6 to 12. Examples of the substituent in the substituted alkyl group include an aryl group, a heterocyclic group, a cycloalkyl group, and an alkoxy group. When the substituted alkyl group has two or more substituents, the respective substituents may be the same or different. The cycloalkyl group may be monocyclic or polycyclic. The number of carbon atoms in the cycloalkyl group is, for example, 5 to 6. Examples of the substituent in the substituted cycloalkyl group include an alkyl group and an alkoxy group. When the substituted cycloalkyl group has two or more substituents, the respective substituents may be the same or different. Examples of the aryl group include Ph. Examples of the substituent in the substituted aryl group include an alkyl group, an alkoxy group, a halogen atom, etc. When the substituted aryl group has two or more substituents, the substituents may be the same or different. The aryl group, cycloalkyl group, and alkyl group as the substituent are the same as those mentioned above. The heterocyclic group as the substituent is, for example, a thienyl group. The alkoxy group as the substituent may be linear or branched. The number of carbon atoms of the alkoxy group is, for example, 1 to 2. The halogen atom as the substituent is, for example, a bromine atom. R 2 As the monovalent hydrocarbon group in 1 The monovalent hydrocarbon groups in R 2 When R is a monovalent hydrocarbon group, 1 and R 2 may be the same or different. Among primary amines and secondary amines, primary amines are preferred, and R 2 is preferably a hydrogen atom. Specific examples of compound (1) include 2-phenylethylamine, 2-(4-methylphenyl)ethylamine, 2-(4-methoxyphenyl)ethylamine, 3-phenylpropylamine, 2-phenylpropylamine, 3,3-diphenylpropylamine, decylamine, cyclopentylamine, 3-ethoxypropylamine, tetrahydrofurfurylamine, adamantylamine, 4-(trifluoromethyl)benzylamine, 2-(4-bromophenyl)ethylamine, benzylamine, hexylamine, and cyclohexylamine.

[0029] An example of the disilylamine or monosilylamine is a compound represented by the following formula (2) (hereinafter also referred to as "compound (2)"). R 3 -NR 4 -SiR 5 R 6 R 7 (2) However, R 3 represents a substituted or unsubstituted monovalent hydrocarbon group, R 4 is SiR 5 R 6 R 7 or a substituted or unsubstituted monovalent hydrocarbon group, R 5 , R 6 and R 7 each independently represents an alkyl group. When the amine compound is compound (2), R 3 -N(R 8 )-C(=O)-N(R 8 )-R 3 The urea compound represented by R 8 is R 4 SiR 5 R 6 R 7 In the case of R 4 When R is a substituted or unsubstituted monovalent hydrocarbon group, 4 By using two or more compounds (2) in combination, the two R 3 , two R 8 It is also possible to obtain urea compounds each having a different structure.

[0030] In formula (2), R 3 and R 4 As the monovalent hydrocarbon group in 1 The monovalent hydrocarbon groups in R 4 When R is a monovalent hydrocarbon group, 3 and R 4 may be the same or different. Among disilylamine and monosilylamine, disilylamine is preferred, and R 4 As for SiR 5 R 6 R7 is preferred. R 5 , R 6 and R 7 The alkyl group in may be linear or branched. The alkyl group has, for example, 1 to 4 carbon atoms. Specific examples of compound (2) include N,N-bis(trimethylsilyl)-N-(2-phenylethyl)amine, N,N-bis(trimethylsilyl)-N-(3-phenylpropyl)amine, N,N-bis(trimethylsilyl)-N-(2-(4-bromophenyl)ethyl)amine, N,N-bis(trimethylsilyl)-N-(2-(4-methylphenyl)ethyl)amine, N,N-bis(trimethylsilyl)-N-benzylamine, N, Examples of such amines include N-bis(trimethylsilyl)-N-hexylamine, N,N-bis(trimethylsilyl)-N-cyclohexylamine, N,N-bis(trimethylsilyl)-N-(2-thienylmethyl)amine, N,N-bis(trimethylsilyl)-N-(2-phenylpropyl)amine, N,N-bis(trimethylsilyl)-N-[(1R)-1-phenylethyl]amine, and N,N-bis(trimethylsilyl)-N-decylamine.

[0031] (Additives) Additives are optionally used for the purpose of improving reaction efficiency, dehydration effect, etc. When the substrate contains at least one selected from the group consisting of primary amines and secondary amines, it is preferable to use additives mainly from the viewpoint of the effect of the base, increasing the concentration of carbon dioxide, and activating the substrate or catalyst. When the substrate contains at least one selected from disilylamines and monosilylamines, it is preferable to use additives mainly from the viewpoint of activating the substrate or catalyst. Examples of additives include phenolic compounds such as phenol, 4-nitrophenol, 4-trifluoromethylphenol, and 4-methoxyphenol; alcoholic compounds such as 2-phenylethyl alcohol; silylation agents such as N,O-bis(trimethylsilyl)acetamide (BSA), 1-trimethylsilyl-1H-imidazole (TMSI), and 1,1,1,3,3,3-hexamethyldisilazane (HMDS); organic bases such as diazabicycloundecene (DBU) and pyridine; inorganic bases such as potassium carbonate and potassium phosphate; inorganic dehydrating agents such as magnesium sulfate, sodium sulfate, and molecular sieve (MS) 3A; and hydrosilanes such as triethoxysilane and triphenylsilane. The silylation agent also functions as an organic dehydrating agent. These additives may be used alone or in combination of two or more.

[0032] From the viewpoint of improving the reaction efficiency, the additive preferably contains at least one selected from the group consisting of potassium carbonate, a silylating agent, a hydrosilane, and a phenolic compound. In particular, when the amine compound contains at least one selected from the group consisting of a primary amine and a secondary amine, it is preferable to contain at least one selected from the group consisting of potassium carbonate, a silylating agent, and a hydrosilane. When the amine compound contains at least one selected from a disilylamine and a monosilylamine, it is preferable to contain a phenolic compound. By using potassium carbonate, the effect of the base and an improvement in the concentration of carbon dioxide can be expected. By using a silylating agent or a hydrosilane, it can be expected to activate the substrate or the catalyst. By using a phenolic compound, it can be expected to activate the substrate or the catalyst. At least one selected from the group consisting of potassium carbonate, a silylating agent, a hydrosilane, and a phenol compound may be used in combination with other additives other than these.

[0033] The amount of the additive used can be appropriately determined depending on the purpose of the additive. For example, the amount of potassium carbonate used is preferably 200 to 2000 mol, and more preferably 200 to 250 mol, in terms of the ratio of potassium carbonate to 100 mol of amino groups of the amine compound. The amount of the silylating agent used is preferably 100 mol or more, more preferably 150 to 250 mol, and even more preferably 200 mol, in terms of the ratio of the silylating agent to 100 mol of amino groups of the amine compound. The amount of hydrosilane used is preferably 100 moles or more, calculated as the ratio of hydrosilane to 100 moles of amino groups of the amine compound. The amount of the phenol compound used is preferably 50 to 200 mol, more preferably 100 to 150 mol, in terms of the ratio of the phenol compound to 100 mol of amino groups of the amine compound.

[0034] (solvent) Examples of the solvent include polar solvents and non-polar solvents. The solvent is preferably a polar solvent that can dissolve the amine compound. By using a polar solvent, the yield of the urea compound can be further increased. Examples of polar solvents include dimethylacetamide (DMA), N,N-dimethylformamide (DMF), N-methylpyrrolidone (NMP), dimethylsulfoxide (DMSO), and dioxane. Among these, DMA, DMF, DMSO, and dioxane are preferred because they provide a higher yield of the urea compound. These polar solvents may be used alone or in combination of two or more.

[0035] The amount of the solvent used is preferably 0 to 1 mL, more preferably 0.1 to 0.5 mL, and most preferably 0.3 mL, relative to 0.3 mmol of the amine compound. When the amount of the solvent used is within the above range, the yield of the urea compound is superior.

[0036] (Reaction of amine compounds with carbon dioxide) As a method for reacting an amine compound with carbon dioxide in the presence of an organic catalyst, a known method can be used, except that the organic catalyst contains a phosphorus organic catalyst A and the amount of the organic catalyst used is within a predetermined range.

[0037] For example, a mixed liquid containing an amine compound, an organic catalyst, and a polar solvent is prepared, and the resulting mixed liquid is brought into gas-liquid contact with a carbon dioxide-containing gas, thereby allowing the amine compound to react with carbon dioxide. The mixed liquid may further contain an additive. The carbon dioxide-containing gas may be carbon dioxide gas or a mixture of carbon dioxide gas and other gases, such as nitrogen gas and oxygen gas. The carbon dioxide-containing gas may be air or exhaust gas. An example of a method for bringing the mixed liquid into gas-liquid contact with the carbon dioxide-containing gas is to place the mixed liquid and the carbon dioxide-containing gas in a container and heat the mixed liquid to a predetermined temperature while stirring.

[0038] The temperature (reaction temperature) when reacting the amine compound with carbon dioxide is, for example, 80 to 140° C., and preferably 100 to 120° C. If the reaction temperature is equal to or higher than the lower limit of the above range, the reaction proceeds easily. If the reaction temperature is equal to or lower than the upper limit of the above range, the energy cost can be reduced, which is industrially advantageous.

[0039] The pressure (reaction pressure) when reacting the amine compound with carbon dioxide is preferably normal pressure (0.10 MPa). The pressure is absolute pressure. If the reaction pressure is normal pressure, no large-scale equipment is required, which is industrially advantageous. EXAMPLES

[0040] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to the following examples. Unless otherwise specified, "mol %" indicates the value in which the molar amount of the amino group of the amine compound is 100 mol %. "Ph" indicates a phenyl group, "Me" indicates a methyl group, "Et" indicates an ethyl group, "i-Pr" indicates an isopropyl group, and "n-Bu" indicates an n-butyl group.

[0041] <Test Example 1> In this test example, we investigated the use of phosphorus organic catalysts in the synthesis of urea compounds using primary amines and atmospheric carbon dioxide as raw materials.

[0042] (Synthesis of urea compounds) In a glove box filled with high-purity nitrogen gas, 2-phenylethylamine (PhCH2CH2-NH2) (0.30 mmol) as a primary amine, phosphorus organic catalyst (P cat.) (0.075 mmol, 25 mol%) shown in Table 1, and dimethylacetamide (DMA) (1.0 mL) were added to a 24-diameter two-neck test tube, and one neck was sealed with a flat stopper and the other neck with a glass three-way cock with a slot. After removing the reaction tube from the glove box, the reaction solution was frozen using liquid nitrogen, and the nitrogen inside the reaction tube was sucked out with a tabletop pump, and carbon dioxide replacement was performed by attaching a balloon filled with carbon dioxide to it. After leaving the reaction solution to stand until it returned to room temperature, it was stirred at 120 °C and 2000 rpm using an organic synthesis apparatus ChemiStation (EYELA personal organic synthesis apparatus, PPS-5511 type). After 24 hours, the supply of carbon dioxide was stopped, and the reaction tube was removed from the organic synthesis apparatus ChemiStation. 1M dilute hydrochloric acid (10mL) was added to the reaction solution, which was then left to stand for 5 minutes, after which the solution was transferred to a separatory funnel containing dichloromethane (30mL) and a separation operation was carried out. Only the organic layer was taken out into a bottle, and the aqueous layer remaining in the separatory funnel was extracted twice with dichloromethane (30mL). Finally, the inside of the separatory funnel was washed with dichloromethane (20mL). The organic layer recovered from the series of separation operations was dehydrated using anhydrous sodium sulfate, and then sodium sulfate hydrate was removed by filtration. Next, the solvent was distilled off under reduced pressure and the mixture was dried in a vacuum. Using 1,3,5-trimethoxybenzene as the internal standard and CDCl3 as the heavy solvent, 1 The yield of the product urea compound was calculated by H NMR measurement. The target product urea compound was purified and isolated by thin layer chromatography. 1 The measurement conditions for H NMR are as follows. Equipment: JEOL JNM-AL400 Solvent: deuterated chloroform (CDCl3) Temperature: 20℃

[0043] (result) Table 1 shows the yield of the urea compound in each example. In Example 1-1, in which diphenylphosphine oxide {HP(=O)Ph2}, a readily available pentavalent phosphorus compound, was used as the catalyst, the target urea compound was obtained in 8% yield. In Examples 1-2 to 1-4, in which HP(=O)(OR)2, which has less steric crowding around the phosphorus atom than diphenylphosphine oxide, was used as a catalyst to improve the reaction efficiency, the target urea compound was obtained in a higher yield (32 to 58%) than in Example 1-1. From these results, it was confirmed that HP(=O)(OR)2 exhibits good catalytic activity. In Example 1-5, in which P(OPh)3 was used as the catalyst, the target urea compound was obtained in a higher yield (45%) than in Example 1-1.

[0044] [Table 1]

[0045] <Test Example 2> In this test example, HP(=O)(OR)2 was used as a catalyst to study additives in the synthesis of urea compounds using primary amines and atmospheric carbon dioxide as raw materials.

[0046] (Synthesis of urea compounds) The same operation as in Example 1-4 of Test Example 1 was carried out except that the additives shown in Table 2 (100 mol% (0.30 mmol) for Examples 2-1 to 2-5, and 200 mol% (0.60 mmol) for Example 2-6) were added to a 24-diameter two-necked test tube together with a primary amine, a phosphorus organic catalyst, and DMA. However, the reaction time for Examples 2-1 to 2-4 was 15 hours.

[0047] (result) The yield of the urea compound in each example is shown in Table 2. The results of Examples 1 to 4 are also shown. In Examples 2-1 and 2-2, in which phenol or 2-phenylethyl alcohol was added, the yield was lower than that of Example 1-4, in which no additive was added, at the reaction time of 15 hours, and no improvement in reaction efficiency was confirmed. However, urea compounds were synthesized with a sufficient yield. The same results were obtained in Example 2-3 in which the hydrosilane HSi(OEt)3 was added. In Example 2-4, in which HSiPh3, another hydrosilane, was added, a slight improvement in reaction efficiency was confirmed after 15 hours of reaction. In Example 2-5, in which the silylating agent N,O-bistrimethylsilylamide was added, an improvement in reaction efficiency was not confirmed, but the urea compound was synthesized in a sufficient yield. In Example 2-6, in which the inorganic dehydrating agent K2CO3 was added, the target urea compound was obtained in a high yield of 68%. From the above investigation, it became clear that phenol compounds, silylating agents, hydrosilanes and K2CO3, with K2CO3 being the most suitable additive.

[0048] [Table 2]

[0049] <Test Example 3> In this test example, HP(=O)(OR)2 was used as a catalyst to study the amount of catalyst in the synthesis of urea compounds using primary amines and atmospheric carbon dioxide as raw materials.

[0050] (Synthesis of urea compounds) The same procedure as in Example 2-6 of Test Example 2 was carried out, except that the amount of phosphorus organic catalyst added to the 24-diameter two-necked test tube was changed to the value (mol%) shown in Table 3.

[0051] (result) The yield of the urea compound in each example is shown in Table 3. The results of Examples 2 to 6 are also shown. In Example 3-1, in which the amount of phosphorus organic catalyst was reduced from 25 mol % to 20 mol %, the reaction efficiency decreased and the yield was 56%. In Example 3-2, in which the amount of phosphorus organic catalyst was increased from 25 mol% to 30 mol%, the reaction efficiency improved and the yield reached 83%.

[0052] [Table 3]

[0053] <Test Example 4> In this test example, HP(=O)(OR)2 was used as a catalyst to investigate the range of substrates (primary amines) applicable to the synthesis of urea compounds using primary amines and atmospheric carbon dioxide as raw materials.

[0054] (Synthesis of urea compounds) The same procedure as in Example 3-2 of Test Example 3 was carried out, except that a primary amine corresponding to the urea compound shown in Table 4 (2-(4-methylphenyl)ethylamine, 2-(4-methoxyphenyl)ethylamine, 3-phenylpropylamine, 2-phenylpropylamine, 3,3-diphenylpropylamine, decylamine, cyclopentylamine, or 3-ethoxypropylamine) was used as the primary amine.

[0055] (result) Table 4 shows the yield of the urea compound in each example. The desired urea compounds were obtained using any of the eight primary amines listed above, and the desired reactions proceeded efficiently in most cases.

[0056] [Table 4]

[0057] <Test Example 5> In this test example, a phosphorus organic catalyst was investigated in the synthesis of a urea compound using disilylamine and atmospheric carbon dioxide as raw materials.

[0058] (Synthesis of urea compounds) In a glove box filled with high-purity nitrogen gas, 2-phenylethyldisilylamine [(PhCH2CH2N(SiMe3)2] (0.30 mmol, 90 μL), phosphorus organic catalyst (P cat.) (0.075 mmol, 25 mol%) shown in Table 5, and dimethylacetamide (DMA) (1.0 mL) were added to a 24-diameter two-neck test tube, and one neck was sealed with a flat stopper and the other neck with a three-way glass cock with a slot. After removing the reaction tube from the glove box, the reaction solution was frozen using liquid nitrogen, and the nitrogen inside the reaction tube was sucked out with a tabletop pump, and a balloon filled with carbon dioxide was attached to replace the nitrogen. The reaction solution was left to stand until it returned to room temperature, and then stirred at 120 °C and 1500 rpm using an organic synthesis apparatus ChemiStation (EYELA personal organic synthesis apparatus, PPS-5511 type). After 24 hours, the supply of carbon dioxide was stopped, and the organic synthesis apparatus Ch The reaction tube was removed from the emiStation. 1M dilute hydrochloric acid (10mL) was added to the reaction solution, and after leaving it for 5 minutes, the solution was transferred to a separatory funnel containing dichloromethane (20mL) and a separation operation was performed. Only the organic layer was taken out into a bottle, and the aqueous layer remaining in the separatory funnel was extracted twice with dichloromethane (20mL). Finally, the inside of the separatory funnel was washed with dichloromethane (20mL). The organic layer recovered from the series of separation operations was dehydrated using anhydrous sodium sulfate, and then sodium sulfate hydrate was removed by filtration. Next, the solvent was distilled off under reduced pressure and the mixture was dried in vacuum. Using 1,3,5-trimethoxybenzene as the internal standard and CDCl3 as the heavy solvent, 1 The yield of the product urea compound was calculated by H NMR measurement. The target product urea compound was purified and isolated by thin layer chromatography. 1 The measurement conditions for H NMR are as follows. Equipment: JEOL JNM-AL400 Solvent: deuterated chloroform (CDCl3) Temperature: 20℃

[0059] (result) Table 5 shows the yield of the urea compound in each example. In Example 5-1, in which diphenylphosphine oxide {HP(=O)Ph2}, a readily available pentavalent phosphorus compound, was used as the catalyst, the desired urea compound was not obtained. In Examples 5-2 to 5-5, the target urea compound was obtained using HP(=O)(OR)2 as a catalyst, which showed good yields when a primary amine was used. From these results, it was confirmed that HP(=O)(OR)2 shows good catalytic activity. In Examples 5-6, in which P(OPh)3 was used as the catalyst, the target urea compound was obtained in good yield. The target urea compounds were also obtained in Examples 5-7 to 5-11, in which phosphorus organic catalysts A other than HP(=O)(OR)2 and P(OPh)3 were used.

[0060] [Table 5]

[0061] <Test Example 6> In this test example, P(OPh)3 was used as a catalyst to study the amount of catalyst in the synthesis of urea compounds using disilylamine and atmospheric carbon dioxide as raw materials.

[0062] (Synthesis of urea compounds) The same procedure as in Example 5-6 of Test Example 5 was carried out, except that the amount of phosphorus organic catalyst added to the 24-diameter two-neck test tube was changed to the value (mol%) shown in Table 6.

[0063] (result) The yield of the urea compound in each example is shown in Table 6. The results of Examples 5 and 6 are also shown. In Examples 6-1 to 6-3, in which the amount of the phosphorus organic catalyst was reduced from 25 mol% to 10 to 20 mol%, and in Example 6-4, in which the amount of the phosphorus organic catalyst was increased from 25 mol% to 30 mol%, the reaction efficiency decreased.

[0064] [Table 6]

[0065] <Test Example 7> In this test example, we used P(OPh)3 as a catalyst and investigated the solvent used in the synthesis of urea compounds using disilylamine and atmospheric carbon dioxide as raw materials.

[0066] (Synthesis of urea compounds) The same procedure as in Example 5-6 of Test Example 5 was carried out, except that the solvent (Solv.) shown in Table 7 was used instead of DMA.

[0067] (result) The yield of the urea compound in each example is shown in Table 7. The results of Examples 5 and 6 are also shown. In Examples 7-1 to 7-3, in which the reactions were carried out using DMF, NMP, and DMSO, which are polar solvents commonly used like DMA, the target urea compounds were obtained in the same manner as in Example 5-6. In Examples 7-4 and 7-5, in which a high-boiling nonpolar solvent was used, a trace amount of the target urea compound was detected.

[0068] [Table 7]

[0069] <Test Example 8> In this test example, P(OPh)3 was used as a catalyst to study the amount of solvent in the synthesis of a urea compound using disilylamine and atmospheric carbon dioxide as raw materials.

[0070] (Synthesis of urea compounds) The same procedure as in Example 6-3 of Test Example 6 was carried out, except that the amount of DMA added to the 24-diameter two-neck test tube was changed to the value (X mL) shown in Table 8.

[0071] (result) The yield of the urea compound in each example is shown in Table 8. The results of Example 6-3 are also shown. In Examples 8-1 to 8-3, in which the amount of the solvent was reduced from 1.0 mL to 0.1 to 0.5 mL, the target urea compound was obtained in a higher yield than in Example 6-3. In Example 8-4, where the reaction was carried out without a solvent, the yield decreased to 20%.

[0072] [Table 8]

[0073] <Test Example 9> In this test example, P(OPh)3 was used as a catalyst to study additives in the synthesis of urea compounds using disilylamine and atmospheric carbon dioxide as raw materials.

[0074] (Synthesis of urea compounds) The same procedure as in Example 8-1 of Test Example 8 was carried out, except that the additives shown in Table 9 (0.30 mmol, 100 mol%) were added to a 24-diameter two-necked test tube together with disilylamine, phosphorus organic catalyst, and DMA.

[0075] (result) The yield of the urea compound in each example is shown in Table 9. The results of Example 8-1 are also shown. In Example 9-1, which used an inorganic base, K2CO3, and in Examples 9-2 and 9-3, which used an organic base, DBU or pyridine, the desired urea compound was obtained, but the yield was lower than that of Example 8-1. In Examples 9-4 to 9-7 in which a phenol compound was used, the target urea compound was obtained in a higher yield than in Example 8-1.

[0076] [Table 9]

[0077] <Test Example 10> In this test example, P(OPh)3 was used as a catalyst to study additives in the synthesis of urea compounds using disilylamine and atmospheric carbon dioxide as raw materials.

[0078] (Synthesis of urea compounds) In a 24-diameter two-necked test tube, disilylamine, phosphorus organic catalyst, and DMA were added together with the additives shown in Table 10 (0.30 mmol, 100 mol%), and the amount of phosphorus organic catalyst was changed to 15 mol%, but the same operation as in Example 8-1 of Test Example 8 was performed.

[0079] (result) Table 10 shows the yield of the urea compound in each example. In Examples 10-1 to 10-4 in which a phenol compound was used, the target urea compound was obtained in a higher yield than in Example 8-1.

[0080] [Table 10]

[0081] <Test Example 11> In this test example, we used P(OPh)3 as a catalyst and investigated the solvent in the synthesis of urea compounds using disilylamine with phenol as an additive and carbon dioxide at normal pressure as raw materials.

[0082] (Synthesis of urea compounds) The same procedure as in Example 10-4 of Test Example 10 was carried out, except that 0.3 mL of a solvent (Solv.) shown in Table 11 was used instead of 0.5 mL of DMA and the reaction temperature was 100°C.

[0083] (result) Table 11 shows the yield of the urea compound in each example. In Examples 11-2 to 11-5, in which the reactions were carried out using DMF, NMP, 1,4-dioxane, and DMSO, which are polar solvents commonly used like DMA, the target urea compounds were obtained in the same manner as in Example 10-4. In Example 11-6, in which a high-boiling nonpolar solvent was used, a small amount of the target urea compound was obtained.

[0084] [Table 11]

[0085] <Test Example 12> In this test example, P(OPh)3 was used as a catalyst to study the amount of additive in the synthesis of a urea compound using disilylamine and atmospheric carbon dioxide as raw materials.

[0086] (Synthesis of urea compounds) The same procedure as in Example 11-4 of Test Example 11 was carried out, except that the amount of additive (phenol) added to the 24-diameter two-neck test tube was changed to the value (mol%) shown in Table 12.

[0087] (result) The yield of the urea compound in each example is shown in Table 12. The results of Example 11-4 are also shown.

[0088] [Table 12]

[0089] <Test Example 13> In this test example, P(OPh)3 was used as a catalyst to investigate the range of substrates (primary amines) applicable to the synthesis of urea compounds using disilylamine and atmospheric carbon dioxide as raw materials.

[0090] (Synthesis of urea compounds) As the primary amine, those corresponding to the urea compounds shown in Table 13 (N,N-bis(trimethylsilyl)-N-(2-phenylethyl)amine, N,N-bis(trimethylsilyl)-N-(2-(4-methylphenyl)ethyl)amine, N,N-bis(trimethylsilyl)-N-(2-(4-bromophenyl)ethyl)amine, N,N-bis(trimethylsilyl)-N-(3-phenylpropyl)amine, N,N-bis(trimethylsilyl)-N-benzylamine, N,N-bis( The same operation as in Example 11-4 of Test Example 11 was carried out, except that N,N-bis(trimethylsilyl)-N-hexylamine, N,N-bis(trimethylsilyl)-N-(3-ethoxypropyl)amine, N,N-bis(trimethylsilyl)-N-cyclohexylamine, N,N-bis(trimethylsilyl)-N-(2-thienylmethyl)amine, N,N-bis(trimethylsilyl)-N-[(1R)-1-phenylethyl]amine, and N,N-bis(trimethylsilyl)-N-decylamine were used.

[0091] (result) The yield of the urea compound in each example is shown in Table 13. The results of Example 11-4 are also shown. The desired urea compounds were obtained using any of the 11 disilylamines listed above, and the desired reactions proceeded efficiently in most cases.

[0092] [Table 13]

[0093] <Test Example 14> In this test example, we used HP(=O)(OR)2 as a catalyst to study additives in the synthesis of urea compounds using disilylamine and atmospheric carbon dioxide as raw materials.

[0094] (Synthesis of urea compounds) The same procedure as in Example 5-4 of Test Example 5 was carried out, except that the additives shown in Table 14 (0.60 mmol, 200 mol%) were added to a 24-diameter two-necked test tube together with disilylamine, phosphorus organic catalyst, and DMA.

[0095] (result) Table 14 shows the yield of the urea compound in each example. In Example 14-1, where K3PO4 was added, the yield was lower than in Example 5-4, where no additive was added. In Examples 14-2 to 14-5, in which DBU, pyridine, K2CO3 or 4-nitrophenol was added, the target urea compound was obtained in a higher yield than in Example 5-4.

[0096] [Table 14]

[0097] <Test Example 15> In this test example, HP(=O)(OR)2 was used as a catalyst to study the amount of catalyst in the synthesis of urea compounds using disilylamine and atmospheric carbon dioxide as raw materials.

[0098] (Synthesis of urea compounds) The same procedure as in Example 14-4 of Test Example 14 was carried out, except that the amount of phosphorus organic catalyst added to the 24-diameter two-neck test tube was changed to the value (mol%) shown in Table 15. In addition, the same procedure as in Example 14-5 of Test Example 14 was performed except that the amount of phosphorus organic catalyst added to the 24-diameter two-neck test tube was changed to the value (mol%) shown in Table 16.

[0099] (result) The yield of the urea compound in each example is shown in Tables 15 and 16. The results of Examples 14-4 and 14-5 are also shown. As shown in Table 15, in a system using K2CO3 as an additive, when the amount of phosphorus organic catalyst was increased from 25 mol% to 30 mol%, the reaction efficiency was lower than that of Example 14-4. When the amount of phosphorus organic catalyst was reduced from 25 mol% to 20 mol%, the reaction efficiency was almost the same as that of Example 14-4. When the amount of phosphorus organic catalyst was reduced from 25 mol% to 15 mol%, the reaction efficiency was lower than that of Example 14-4. As shown in Table 16, in a system using 4-nitrophenol as an additive, when the amount of the phosphorus organic catalyst was reduced from 25 mol%, the reaction efficiency was lower than that in Example 14-5.

[0100] [Table 15]

[0101] [Table 16]

[0102] <Test Example 16> In this test example, HP(=O)(OR)2 was used as a catalyst to study the amount of additive in the synthesis of a urea compound using disilylamine and atmospheric carbon dioxide as raw materials.

[0103] (Synthesis of urea compounds) The same procedure as in Example 14-5 of Test Example 14 was carried out, except that the amount of additive (4-nitrophenol) added to the 24-diameter two-neck test tube was changed to the value (mol%) shown in Table 17.

[0104] (result) The yield of the urea compound in each example is shown in Table 17. The results of Example 14-5 are also shown. As shown in Table 17, even when the amount of additive was reduced to 25 to 100 mol %, the target urea compound was obtained in high yield.

[0105] [Table 17]

[0106] <Test Example 17> In this test example, HP(=O)(OR)2 was used as a catalyst to investigate the use of multiple additives in the synthesis of urea compounds using disilylamine and atmospheric carbon dioxide as raw materials.

[0107] (Synthesis of urea compounds) The same procedure as in Test Example 14 was performed except that the amount of phosphorus organic catalyst was changed to the amount shown in Table 18, and K2CO3 and 4-nitrophenol were used as additives in the amounts shown in Table 18.

[0108] (result) Table 18 shows the yield of the urea compound in each example. As shown in Table 18, even when multiple additives were used in combination, the target urea compound was obtained in high yield.

[0109] [Table 18]

[0110] <Test Example 18> In this test example, 1-trimethylsilyl-1H-imidazole (TMSI) was used as an additive to study the effect of phosphorus organocatalysts in the synthesis of urea compounds using primary amines and atmospheric carbon dioxide as raw materials.

[0111] (Synthesis of urea compounds) The same procedure as in Example 11-4 of Test Example 11 was carried out, except that the additive was changed from phenol to TMSI and an organophosphorus catalyst shown in Table 19 was used instead.

[0112] (result) Table 19 shows the yield of the urea compound in each example.

[0113] [Table 19]

[0114] <Test Example 19> In this test example, a silylating agent was investigated as an additive in the synthesis of a urea compound using primary amines and atmospheric carbon dioxide as raw materials.

[0115] (Synthesis of urea compounds) The same procedure as in Example 18-4 of Test Example 18 was carried out, except that the additive was changed from TMSI to a silylating agent shown in Table 20.

[0116] (result) The yield of the urea compound in each example is shown in Table 20. The results of Example 18-4 are also shown.

[0117] [Table 20] [Industrial Applicability]

[0118] According to the present invention, it is possible to provide an efficient method for producing a urea compound based on carbon dioxide activation using an organic catalyst. The urea compound obtained by the method for producing a urea compound of the present invention can be widely used as a raw material for herbicides, agricultural chemicals, medicines, insecticides, polyurethanes, and various other resins.

Claims

1. A method for producing a urea compound, comprising reacting an amine compound with carbon dioxide in the presence of an organic catalyst, the organic catalyst comprises at least one phosphorus organic catalyst selected from the group consisting of esters of phosphorus oxoacids and phosphine oxides; The method for producing a urea compound, wherein a ratio of the organic catalyst to 100 moles of amino groups of the amine compound is more than 0 mole and less than 100 moles.

2. 2. The method for producing a urea compound according to claim 1, wherein the amine compound is at least one selected from the group consisting of a primary amine, a secondary amine, a disilylamine and a monosilylamine.

3. The method for producing a urea compound according to claim 1, wherein the amine compound is at least one selected from the group consisting of compounds represented by the following formula (1) and compounds represented by the following formula (2): R １ -NH-R ２ ・・・(1) R ３ -NR ４ -SiR ５ R ６ R ７ ・・・(2) However, R １ represents a substituted or unsubstituted monovalent hydrocarbon group; R ２ represents a hydrogen atom or a substituted or unsubstituted monovalent hydrocarbon group, R ３ represents a substituted or unsubstituted monovalent hydrocarbon group; R ４ is SiR ５ R ６ R ７ or a substituted or unsubstituted monovalent hydrocarbon group, R ５ , R ６ and R ７ each independently represents an alkyl group.

4. 2. The method for producing a urea compound according to claim 1, wherein a ratio of the organic catalyst to 100 moles of the amino groups is 10 to 30 moles.

5. 2. The method for producing a urea compound according to claim 1, wherein the pressure when the amine compound and the carbon dioxide are reacted is normal pressure.

6. 2. The method for producing a urea compound according to claim 1, wherein the temperature during the reaction of the amine compound with the carbon dioxide is 80 to 140° C.

7. The method for producing a urea compound according to claim 1 , comprising reacting the amine compound with the carbon dioxide in the presence of the organic catalyst and the additive.

8. The method for producing a urea compound according to claim 1, comprising reacting the amine compound with the carbon dioxide in the presence of the organic catalyst and a polar solvent.

9. 9. The method for producing a urea compound according to claim 8, further comprising the steps of: preparing a mixed solution containing the amine compound, the organic catalyst, and the polar solvent; and bringing the mixed solution into gas-liquid contact with a carbon dioxide-containing gas, thereby reacting the amine compound with the carbon dioxide.

10. The method for producing a urea compound according to claim 9, wherein the mixed solution further contains an additive.

11. The method for producing a urea compound according to claim 7 or 10, wherein the additive comprises at least one selected from the group consisting of potassium carbonate, a silylating agent, a hydrosilane, and a phenol compound.

12. the amine compound includes at least one selected from the group consisting of disilylamine and monosilylamine, The method for producing a urea compound according to claim 7 or 10, wherein the additive comprises a phenol compound.

13. the amine compound includes at least one selected from the group consisting of primary amines and secondary amines, The method for producing a urea compound according to claim 7 or 10, wherein the additive comprises at least one selected from the group consisting of potassium carbonate, a silylating agent, and a hydrosilane.

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