Method of producing halogenated carbonyl compound, and method of producing carbonyl compound

Abstract

To provide a method of producing a halogenated carbonyl compound, capable of further highly efficiently producing a halogenated carbonyl compound from a halogenated hydrocarbon via a radical reaction, and a method of producing a carbonyl compound, capable of producing an intended carbonyl compound with a higher purity.SOLUTION: There are provided a method of producing a halogenated carbonyl compound, including the production of a halogenated carbonyl compound from a mixed solution including an organic radical generator and a halogenated hydrocarbon by a radical reaction in the presence of oxygen, and a method of producing a carbonyl compound, including the reaction of the halogenated carbonyl compound obtained by the production method with an active hydrogen containing compound. The organic radical generator includes neither an organic peroxide nor an azo compound.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a method for producing a carbonyl compound having a halogenated structure, and a method for producing a carbonyl compound using the carbonyl compound obtained by the method as a reactant. [Background technology]

[0002] Carbonyl halide compounds are known as reactants for introducing carbonyl groups into various compounds containing active hydrogen, and phosgene is widely used as such a reactant. For example, isocyanate compounds, urea compounds, etc. can be obtained by reacting phosgene with primary amines. In addition, carbonate compounds, chloroformate compounds, etc. can be obtained by reacting phosgene with compounds having a hydroxyl group. Carbonyl halide compounds are highly toxic, and many of them are gaseous at room temperature, so they must be handled with the utmost care.

[0003] Several methods for synthesizing carbonyl halide compounds have been proposed. For example, the industrial synthesis of phosgene is carried out by the gas reaction of carbon monoxide and chlorine, which requires high temperatures of over 350°C and is carried out in a dedicated plant. A method of producing phosgene from solid triphosgene by a catalytic reaction is also known (see, for example, Patent Documents 1 and 2). This method does not require high temperatures and allows phosgene to be synthesized relatively easily on demand, but has the disadvantage that triphosgene is expensive. Furthermore, Patent Document 3 describes a method for obtaining carbonyl halides such as phosgene by irradiating a liquid composition containing halogenated hydrocarbons with light in the presence of oxygen and a specific substance (chlorine gas, sodium chlorite, etc.) that generates radicals when exposed to visible light. The technology described in Patent Document 3 is said to enable efficient production of carbonyl halides through a radical reaction without requiring high temperatures and simply by irradiating visible light from a white LED light source. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] International Publication No. 2021 / 033504 [Patent Document 2] International Publication No. 2021 / 033505 [Patent Document 3] International Publication No. 2021 / 045105 Summary of the Invention [Problem to be solved by the invention]

[0005] In a specific embodiment of the method for producing a carbonyl halide compound via a radical reaction described in Patent Document 3, chlorine gas, sodium chlorite, or the like is used as a radical generator. The present inventors have investigated the efficiency of producing a carbonyl halide compound from a halogenated hydrocarbon using these specific radical generators, using as an index the efficiency of producing a carbonyl compound by using the produced carbonyl halide compound as a reactant. As a result, it has been found that although the target carbonyl compound can be obtained relatively efficiently, a certain amount of impurities is also produced.

[0006] The present invention aims to provide a method for producing a halogenated carbonyl compound, which can produce a halogenated carbonyl compound more efficiently from a halogenated hydrocarbon via a radical reaction. Another objective of the present invention is to provide a method for producing a carbonyl compound, which can obtain a target carbonyl compound with a higher purity by using a halogenated carbonyl compound as a reactant. [Means for solving the problem]

[0007] The present inventors have conducted extensive research in view of the above problems. As a result, they have found that when a specific organic radical generator is used as a radical generator in producing a halogenated carbonyl compound from a halogenated hydrocarbon through a radical reaction, the efficiency of producing the halogenated carbonyl compound or the target carbonyl compound obtained by reacting with this compound is significantly increased. Based on these findings, the present invention has been completed through further research.

[0008] The above object of the present invention is achieved by the following means. [1] A method for producing a halogenated carbonyl compound, comprising generating the halogenated carbonyl compound from a mixed liquid containing an organic radical generator and a halogenated hydrocarbon by a radical reaction in the presence of oxygen. However, the organic radical generator does not include any of organic peroxides and azo compounds. [2] The method for producing a carbonyl halide compound according to [1], wherein the radical reaction in the presence of oxygen is a radical reaction in an air atmosphere. [3] The method for producing a carbonyl halide compound according to [1] or [2], wherein the oxygen is supplied by supplying air into the mixed liquid. [4] The method for producing a carbonyl halide compound according to any one of [1] to [3], wherein the organic radical generator generates radicals by supplying light and / or heat to the mixed solution, thereby causing the radical reaction. [5] The method for producing a carbonyl halide compound according to [4], wherein the light is light from a light emitting diode light source. [6] The method for producing a carbonyl halide compound according to any one of [1] to [5], wherein the organic radical generator contains the following (a) and / or (b): (a) A compound that generates halogen radicals by breaking chemical bonds in response to an external stimulus, (b) Compounds having a phenylcarbonyl structure. [7] The method for producing a carbonyl halide compound according to [6], wherein the compound (a) has a structural part represented by the following formula (1): *-C(=O)-N(-X)-C(=O)-* Formula (1) In the formula, X represents a halogen atom, and * represents a bond. [8] The method for producing a halogenated carbonyl compound according to any one of [1] to [7], wherein the halogen atom in the halogenated hydrocarbon is an atom selected from chlorine, bromine and iodine. [9] The method for producing a carbonyl halide compound according to [8], wherein the halogenated hydrocarbon is chloroform and the carbonyl halide compound is phosgene.

[10] A method for producing a carbonyl compound, comprising reacting a carbonyl compound obtained by the method for producing a carbonyl compound according to any one of [1] to [9] with an active hydrogen-containing compound.

[11] The method for producing a carbonyl compound according to

[10] , wherein the active hydrogen-containing compound is at least one of a primary amine compound, a secondary amine compound, an alcohol compound, a thiol compound, a carboxylic acid compound, and an amino acid.

[0009] In this specification, a numerical range expressed using "to" means a range that includes the numerical values ​​before and after "to" as the lower and upper limits. Effect of the Invention

[0010] According to the method for producing a halogenated carbonyl compound of the present invention, a halogenated carbonyl compound can be obtained more efficiently from a halogenated hydrocarbon through a radical reaction. Also, according to the method for producing a carbonyl compound of the present invention, a target carbonyl compound can be obtained with a higher purity by using a halogenated carbonyl compound as a reactant. [Brief description of the drawings]

[0011] [Figure 1] FIG. 1 is a diagram showing a presumed reaction scheme for a reaction of producing phosgene as a carbonyl halide compound using chloroform as a halogenated hydrocarbon. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] [Method of producing halogenated carbonyl compounds] The method for producing a halogenated carbonyl compound of the present invention (hereinafter also referred to as "production method (I) of the present invention") comprises generating a halogenated carbonyl compound from a mixed solution containing a specific organic radical generator and a halogenated hydrocarbon by a radical reaction in the presence of oxygen. In the present invention, a "halogenated carbonyl compound" is a compound having a structure in which a halogen atom and a carbonyl group are directly bonded to each other. As an example of the reaction for producing the above-mentioned carbonyl halide compound, a presumed reaction scheme for a reaction for obtaining phosgene, a carbonyl halide, using chloroform as a halogenated hydrocarbon is shown in FIG.

[0013] In the reaction scheme shown in Figure 1, in the above-mentioned mixed solution, the specific organic radical generator specified in this invention generates a radical (·R) in response to external stimuli such as light and heat, and this radical abstracts hydrogen from chloroform (CHCl3), and the resulting CCl3 radical (·CCl3) combines with oxygen (O2), and then phosgene (COCl2) is produced with the release of oxygen (1 / 2O2) and a chlorine radical (·Cl). The production method (I) of the present invention will now be described in more detail.

[0014] <Organic radical generator> In the production method (I) of the present invention, the organic radical generator is an organic compound that generates radicals by breaking a chemical bond (covalent bond) in response to an external stimulus. By using a specific organic radical generator instead of an inorganic radical generator, the efficiency of generating a halogenated carbonyl compound is improved, and the purity of the obtained carbonyl compound can be effectively increased by using the generated halogenated carbonyl compound in various carbonyl group introduction reactions. Although the reason for this is unclear, one of the reasons is thought to be that inorganic radical generators such as chlorine and sodium chlorite also act as strong oxidizing agents, and unintended oxidation reactions other than the target reaction occur, which easily generates by-products. A similar oxidation reaction is likely to occur when an organic peroxide such as benzoyl peroxide is used as an organic radical generator, so in the present invention, the organic radical generator is specified to be free of organic peroxides. In addition, although azo compounds such as azobisisobutyronitrile are generally used as organic radical generators, in the present invention, it is also specified that the organic radical generator is free of azo compounds. This is because the use of azo compounds may induce side reactions via amines generated by decomposition of the azo group.

[0015] The organic radical generator used in the production method (I) of the present invention is preferably a compound that generates radicals by light and / or heat, and more preferably a compound that generates radicals by light. An organic radical generator that generates a sufficient amount of radicals even with light from a light-emitting diode (LED) light source with low energy consumption is more preferable because it has a smaller environmental impact.

[0016] The organic radical generator used in the production method (I) of the present invention preferably contains the following (a) and / or (b): (a) A compound that generates halogen radicals by breaking chemical bonds in response to an external stimulus, (b) Compounds having a phenylcarbonyl structure (a structure in which a carbonyl group is bonded to a carbon atom constituting a benzene ring).

[0017] The above compound (a) may be, for example, a compound used as a so-called halogenating agent in various chemical reactions. The above compound (a) preferably has a structural part represented by the following formula (1). *-C(=O)-N(-X)-C(=O)-* Formula (1) In the formula, X represents a halogen atom, and * represents a bond. X is preferably a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom, more preferably a chlorine atom or a bromine atom, and further preferably a chlorine atom.

[0018] Examples of the compound (b) include compounds generally known as photoradical initiators, thermal radical initiators, or sensitizers.

[0019] The organic radical generator has a molecular weight of preferably 80-1,000, more preferably 100-500, and further preferably 120-300.

[0020] The compound (a) may have the phenylcarbonyl structure defined in (b) above, in which case the compound is classified as the compound (a) above.

[0021] Preferred specific examples of the organic radical generator used in the production method (I) of the present invention are shown below, but the present invention is not limited to the following specific examples except as specified in the present invention. In the following examples, "organic radical generator" is simply written as "radical agent" and numbered. Radical agents 1-1 to 1-14 are compounds known as chlorinating agents or brominating agents, radical agents 2-1 to 2-10 are compounds known as sensitizers, and radical agents 3-1 to 3-6 are compounds known as radical initiators in radical polymerization reactions. In the following specific examples, Me represents methyl, Et represents ethyl, and Ph represents phenyl.

[0022] [ka]

[0023] [ka]

[0024] [ka]

[0025] In the production method (I) of the present invention, the amount of the organic radical generator to be used is, in terms of molar ratio, the following relative to the amount of the halogenated hydrocarbon to be used: 0.0005 / 100≦amount of organic radical generator used / halogenated hydrocarbon≦20 / 100 is preferred, 0.0010 / 100≦amount of organic radical generator used / halogenated hydrocarbon≦15 / 100 is more preferable, 0.0015 / 100≦amount of organic radical generator used / halogenated hydrocarbon≦12 / 100 is more preferable, 0.0020 / 100≦amount of organic radical generator used / halogenated hydrocarbon≦10 / 100 is more preferable, It is more preferable that 0.0030 / 100≦amount of organic radical generator used / halogenated hydrocarbon≦8 / 100. 0.0040 / 100≦amount of organic radical generator used / halogenated hydrocarbon≦6 / 100 is more preferable, 0.0050 / 100≦amount of organic radical generator used / halogenated hydrocarbon≦4 / 100 is more preferable, It is more preferable that 0.0060 / 100≦amount of organic radical generator used / halogenated hydrocarbon≦2 / 100.

[0026] When light is used as the external stimulus, the radical agent may contain a photosensitizer. By using the radical agent and the photosensitizer in combination, the efficiency of light (photons) utilization is improved, and the efficiency of radical generation from the radical agent is improved. Preferred examples of the sensitizer include aromatic nitro compounds, coumarin, ketocoumarin, carbonyl biscoumarin, aromatic 2-hydroxyketones, acetophenone, anthraquinone, xanthone, thioxanthone, benzanthrone, thiazoline, benzothiazole, nitroaniline, nitroacenaphthene, benzothiazole, benzoin alkyl ether, N-alkylated phthalone, acetophenone ketal, naphthalene, anthracene, benzopyran, azoindolizine, merocoumarin, acridine, xanthene, phenoxazine, phenothiazine, phenazine, oxazine, methylene green, methylene blue, xanthone, thioxanthone, acridone, camphorquinone, aminobenzoic acid esters, and the like, or derivatives having these skeletons. One or more of these can be used.

[0027] <Halogenated hydrocarbons> The halogenated hydrocarbon used in the production method (I) of the present invention is a compound in which all or part of the hydrogen atoms of a hydrocarbon are substituted with halogen atoms. The halogenated hydrocarbon is liquid under the reaction conditions of the production method (I) of the present invention, and is preferably liquid at room temperature (25°C) and normal pressure (0.10 MPa). In the production method (I) of the present invention, the halogenated hydrocarbon may be used alone or in combination of two or more kinds.

[0028] The halogen atom contained in the halogenated hydrocarbon is preferably an atom selected from chlorine, bromine and iodine. Preferred examples of the halogenated hydrocarbon include monohalomethane (CH3X), dihalomethane (CH2X2), trihalomethane (CHX3), tetrahalomethane (CX4), monohaloethane (C2H5X), dihaloethane (C2H4X2), trihaloethane (C2H3X3), tetrahaloethane (C2H2X4), monohaloethylene (C2H3X), dihaloethylene (C2H2X2), trihaloethylene (C2HX3), tetrahaloethylene (C2X4) (X is a halogen atom, preferably a chlorine atom, bromine atom or iodine atom, more preferably a chlorine atom or bromine atom, and even more preferably a chlorine atom), and the like.

[0029] Specific preferred examples of the halogenated hydrocarbon include fluoromethane (CH3F), difluoromethane (CH2F2), trifluoromethane (CHF3, also called fluoroform), chloromethane (CH3Cl), dichloromethane (CH2Cl2, also called methylene chloride), trichloromethane (CHCl3, also called chloroform), tetrachloromethane (CCl4, also called carbon tetrachloride), dichloroethane (C2H4Cl2), tetrachloroethane (C2H2Cl4), chloroethylene (C2H3Cl), dichloroethylene (C2H2Cl), Examples of bromoethane include methylene chloride (C2H2Cl2), trichloroethylene (C2HCl3), tetrachloroethylene (C2Cl4), bromomethane (CH3Br), dibromomethane (CH2Br2, also known as methylene bromide), tribromomethane (CHBr3, also known as bromoform), tetrabromomethane (CBr4, also known as carbon tetrabromide), dibromoethane (C2H4Br2), tetrabromoethane (C2H2Br4), iodomethane (CH3I), diiodomethane (CH2I2), and triiodomethane (CHI3, also known as iodoform). Of these, the halogenated hydrocarbon is preferably chloroform, dichloromethane or bromoform, and more preferably chloroform.

[0030] <Radical reactions in the presence of oxygen> In the present invention, the radical reaction in the presence of oxygen means that a mixed liquid containing an organic radical generator and a halogenated hydrocarbon is subjected to a radical reaction under an oxygen-containing gas atmosphere. The oxygen-containing gas may be oxygen itself or a mixed gas of oxygen and a gas other than oxygen. In the mixed gas of oxygen and a gas other than oxygen, the gas other than oxygen is preferably an inert gas. More preferably, the mixed gas is air. Therefore, a preferred embodiment of the production method (I) of the present invention includes producing a halogenated carbonyl compound from a mixed liquid containing an organic radical generator and a halogenated hydrocarbon by a radical reaction under an air atmosphere.

[0031] As a method of placing the mixed liquid in the presence of oxygen, in the case of a batch-type reaction system, a method of contacting the liquid surface of the mixed liquid with an oxygen-containing gas or bubbling the oxygen-containing gas into the mixed liquid can be used. A flow reaction can also be applied. In this case, a flow path through which the mixed liquid flows and a flow path through which the oxygen-containing gas flows can be merged. A carbonyl halide compound is generated by causing a radical reaction in the presence of oxygen in the merged liquid (merged gas-liquid). The amount of oxygen supplied in the radical reaction may be appropriately adjusted so as to obtain a desired reaction efficiency.

[0032] The radical reaction proceeds in a chain reaction as a result of the organic radical generator being cleaved by applying an external stimulus to the mixed solution to generate radicals. Examples of the external stimulus include light, heat, electric current, electric field (voltage), magnetic field, and mechanical pressure. From the viewpoint of convenience, it is preferable to generate radicals from the organic radical generator by supplying light and / or heat, and it is more preferable to generate radicals from the organic radical generator by supplying light.

[0033] The supply of light can be carried out by irradiating the mixed solution with various light sources. The light source is not particularly limited, and natural light such as sunlight, a xenon lamp, a halogen lamp, a fluorescent lamp (hot cathode fluorescent lamp), a cold cathode fluorescent lamp (CCFL), a mercury lamp, a light-emitting diode (LED) light source, a metal halide lamp, an electrodeless lamp, a sodium lamp, an arc lamp, a neon tube, an incandescent light bulb, a laser light, etc. can be appropriately used. In consideration of energy efficiency and wavelength control, etc., it is preferable to use an LED light source or a cold cathode fluorescent lamp (CCFL). The wavelength and intensity of the irradiated light are not particularly limited as long as the energy for cleaving the organic radical generator to generate radicals can be imparted, and can be appropriately set according to the purpose. The wavelength of the irradiated light in the radical reaction can be, for example, 200 nm or more, and preferably 230 nm or more. In addition, this wavelength can be, for example, 800 nm or less, 700 nm or less, 600 nm or less, or 500 nm or less. That is, the irradiated light in the radical reaction can be ultraviolet light, visible light, or infrared light, and from the viewpoint of reaction efficiency, ultraviolet light (preferably with a wavelength of 230 to 420 nm) is preferable. As a light source of ultraviolet light, it is preferable to use an LED light source or a cold cathode fluorescent lamp (CCFL) from the viewpoint of energy efficiency. In addition, a white light source can also be used, and a white LED light source can be preferably used.

[0034] For example, in the batch reaction, it is preferable to apply an external stimulus to the mixed solution by irradiating it with light or applying heat. This external stimulus is preferably applied while supplying oxygen to the mixed solution (preferably while bubbling oxygen), and more preferably while supplying the oxygen by supplying air to the mixed solution (preferably while bubbling air). The oxygen or air is preferably supplied continuously. By applying the external stimulus to the mixed solution while continuously supplying oxygen or air to the mixed solution, the desired radical reaction proceeds, and, for example, a gaseous carbonyl halide compound is produced. In addition, in the flow reaction, as described above, a flow path through which the mixed liquid flows and a flow path through which a gas containing oxygen flows can be merged. Therefore, by applying the above-mentioned external stimulus to the mixed liquid before the merging or to the merged liquid after the merging (merged gas-liquid), the target radical reaction proceeds in the merged liquid, and, for example, a gaseous carbonyl halide compound is generated.

[0035] In the production method (I) of the present invention, since the halogenated hydrocarbon can also serve as the solvent, it is not necessary to use an additional solvent, but a solvent other than the halogenated hydrocarbon raw material may be used as appropriate within a range that does not impair the effects of the present invention. From the viewpoints of reaction efficiency, convenience, etc., it is preferable not to use the above-mentioned solvent.

[0036] In the production method (I) of the present invention, a carbonyl halide compound is generated according to the type of halogenated hydrocarbon used. Examples of the carbonyl halide compound generated include carbonyl difluoride, phosgene (carbonyl dichloride), carbonyl dibromide, carbonyl diiodide, oxalyl chloride, oxalyl bromide, oxalyl iodide, formic acid chloride, formic acid bromide, and formic acid iodide. Among them, it is preferred that the halogenated hydrocarbon is a chlorinated hydrocarbon (preferably chloroform and / or dichloromethane) and the carbonyl halide compound produced is phosgene, or that the halogenated hydrocarbon is a brominated hydrocarbon (preferably bromoform and / or dibromomethane) and the carbonyl halide compound produced is carbonyl dibromide, and it is more preferred that the halogenated hydrocarbon is a chlorinated hydrocarbon and the carbonyl halide compound produced is phosgene. Therefore, a more preferred embodiment of the production method (I) of the present invention can be specified as follows.

[0037] A method for producing phosgene, comprising generating phosgene from a mixed liquid containing an organic radical generator and a chlorinated hydrocarbon by a radical reaction in the presence of oxygen. However, the organic radical generator does not include any of organic peroxides and azo compounds.

[0038] In the production method (I) of the present invention, the reaction temperature of the radical reaction can be appropriately set in consideration of the desired liquid phase reaction, the necessary heating level when generating radicals by thermal stimulation, etc. The reaction temperature of the radical reaction can be, for example, -80 to 60°C, and from the viewpoint of energy efficiency, -40 to 50°C is preferable, -30 to 45°C is more preferable, and -20 to 40°C is even more preferable. The reaction time of the radical reaction is not particularly limited, and can be appropriately adjusted so that the desired carbonyl halide compound can be obtained in the desired amount or with the desired efficiency.

[0039] The atmospheric pressure during the radical reaction is not particularly limited, and is preferably 0.10 MPa or more, more preferably 0.10 to 1.00 MPa, even more preferably 0.10 to 0.80 MPa, even more preferably 0.10 to 0.60 MPa, and even more preferably 0.10 to 0.50 MPa.

[0040] [Method of producing carbonyl compounds] The method for producing a carbonyl compound of the present invention (hereinafter also referred to as Production Method (II) of the present invention) utilizes the above-mentioned Production Method (I) of the present invention. That is, it includes reacting a carbonyl halide compound obtained by Production Method (I) of the present invention with an active hydrogen-containing compound. In Production Method (II) of the present invention, the term "carbonyl compound" is used in a sense that does not include the carbonyl halide compound obtained by Production Method (I) of the present invention that is used in Production Method (II) of the present invention.

[0041] In the production method (II) of the present invention, it is preferable that the reaction between the carbonyl halide compound obtained by the production method (I) of the present invention and the active hydrogen-containing compound is carried out in a reaction system different from that of the production method (I) of the present invention. That is, it is preferable to separate the carbonyl halide compound obtained by the production method (I) of the present invention from the reaction system of the production method (I) of the present invention, and to feed the separated carbonyl halide compound to a reaction system different from that of the production method (I) of the present invention to react with the active hydrogen-containing compound. In this way, it is possible to more reliably prevent the reaction residue in the production method (I) of the present invention from affecting the reaction between the carbonyl halide compound and the active hydrogen-containing compound. In the production method (I) of the present invention, a liquid phase reaction is carried out, while the carbonyl halide compound produced is usually in a gaseous state. Therefore, the carbonyl halide compound obtained by the production method (I) of the present invention can be easily separated from the reaction system of the production method (I) of the present invention, whether the reaction system of the production method (I) of the present invention is a batch type or a flow type. For example, in the case of a batch type, the gas phase in the reaction vessel (i) used in the production method (I) of the present invention and the gas phase in the reaction vessel (ii) used for the reaction of the carbonyl halide compound and the active hydrogen-containing compound are connected via a tube or the like, so that the carbonyl halide compound present in the gas phase of the reaction vessel (i) can be easily sent into the reaction vessel (ii). If the tip of the tube introduced into the reaction vessel (ii) is inserted into a reaction substrate liquid obtained by dissolving the active hydrogen-containing compound in a solvent, the reaction substrate liquid can be bubbled with a gas containing the carbonyl halide compound, and the reaction can be carried out more efficiently.

[0042] The reaction between the carbonyl halide compound and the active hydrogen-containing compound can be carried out by contacting the carbonyl halide compound with a reaction substrate liquid obtained by dissolving the active hydrogen-containing compound in a solvent. Neutralizing agents, stabilizers, etc. can be added to this reaction system as necessary. For example, if the carbonyl halide compound is phosgene, hydrochloric acid is generated as a by-product, so that a neutralizing agent such as a tertiary amine compound can be allowed to coexist in the reaction system.

[0043] The reaction between the carbonyl halide compound and the active hydrogen-containing compound can be carried out as a batch reaction or a flow reaction, similarly to the reaction system of Production Method (I) of the present invention. As a batch reaction, for example, a reaction substrate liquid obtained by dissolving the active hydrogen-containing compound in a solvent is prepared in a reaction vessel, and the reaction substrate liquid is bubbled with a gas containing a carbonyl halide compound as described above. In addition, as a flow reaction, a flow path through which the reaction substrate liquid flows and a flow path through which a gas containing a carbonyl halide compound flows can be merged. In the merged liquid (merged gas-liquid), the carbonyl halide compound reacts with the active hydrogen-containing compound to produce the target carbonyl compound.

[0044] <Active hydrogen-containing compounds> The active hydrogen-containing compound is not particularly limited as long as it has active hydrogen in the molecule. For example, compounds having at least one group selected from -OH, -COOH, -NH2, -NHR (R is a substituent) and -SH can be widely used. The active hydrogen-containing compound is, for example, at least one compound selected from primary amine, secondary amine, alcohol, thiol, carboxylic acid and amino acid. The carbonyl group introduction reaction by the reaction of these active hydrogen-containing groups with a halogenated carbonyl compound such as phosgene is known per se, and the reaction conditions are appropriately set according to the target reaction. For example, an isocyanate compound, a carbamoyl chloride compound, a urea compound, etc. can be obtained by the reaction of a compound having an amino group with phosgene. In addition, a carbonate compound, a chloroformate compound, etc. can be obtained by the reaction of a compound having a hydroxyl group with phosgene. In addition, an acid chloride compound can be obtained by the reaction of a compound having a carboxyl group with phosgene. In addition, an amino acid anhydride can be obtained by the reaction of an amino acid with phosgene. The reaction product of a halogenated carbonyl compound other than phosgene with an active hydrogen-containing compound can also be obtained in the same manner as above. Examples of halogenated carbonyl compounds other than phosgene include oxalyl chloride and acetyl chloride, which can be reacted with an active hydrogen-containing group such as an amino group or a hydroxyl group to obtain an amide compound, an ester compound, etc., in the same manner as the reaction with phosgene. Of these, the active hydrogen-containing compound is preferably a primary amine, a secondary amine, an alcohol, or an amino acid. The active hydrogen-containing compound serving as the reaction substrate preferably has a molecular weight of 40-1,000, more preferably 60-500.

[0045] <Solvent> Examples of the solvent used in the reaction substrate liquid include halogen-containing solvents, ether solvents having a straight-chain, branched-chain or cyclic structure, and hydrocarbon solvents. Examples of halogen-containing solvents include methylene chloride, chloroform, dichloroethane, carbon tetrachloride, chlorobenzene, and o-dichlorobenzene. Examples of the ether solvent include tetrahydrofuran, dioxane, methyl tertiary butyl ether, cyclopentyl methyl ether, ethylene glycol dibutyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, diethylene glycol dibutyl ether, and derivatives thereof. Examples of the hydrocarbon solvent include hexane, heptane, octane, cyclohexane, methylcyclohexane, benzene, toluene, xylene, mesitylene, decalin, tetralin, and derivatives thereof. In addition, as the solvent, ketone-based solvents such as acetone, methyl ethyl ketone, diisobutyl ketone, cyclohexanone, and methyl isobutyl ketone, nitrile-based solvents such as acetonitrile, lactone-based solvents such as γ-butyrolactone, ester-based solvents such as ethyl acetate and butyl acetate, and amide-based solvents such as dimethylacetamide and dimethylformamide can also be used. The above solvents may be used alone or in the form of a mixed solvent of two or more kinds.

[0046] In the production method (II) of the present invention, the reaction between the carbonyl halide compound and the active hydrogen-containing compound can be carried out such that the concentration of the active hydrogen-containing compound in the reaction substrate liquid is, for example, 0.0001 to 50 M (mol / L), preferably 0.01 to 10 M, more preferably 0.02 to 5 M, even more preferably 0.04 to 3 M, and even more preferably 0.06 to 1 M.

[0047] In the production method (II) of the present invention, the reaction temperature between the carbonyl halide compound and the active hydrogen-containing compound, the reaction time, the amount of the carbonyl halide compound introduced, etc. are not particularly limited, and can be appropriately set in consideration of the amount of the target product, the reaction efficiency, etc. For example, the reaction temperature can be −80 to 100° C., preferably −60 to 60° C., more preferably −40 to 50° C., and further preferably −30 to 40° C. In the reaction between the carbonyl halide compound and the active hydrogen-containing compound, the carbonyl halide compound is preferably continuously introduced into the reaction substrate liquid.

[0048] The present invention will be described in more detail with reference to examples. However, the present invention is not limited to these examples except as defined in the present invention. EXAMPLES

[0049] [Example 1] The carbonyl compounds were prepared according to the following reaction scheme:

[0050] [ka]

[0051] A 20 mL Schlenk flask was prepared as a reaction vessel (i). Into the reaction vessel (i), 1.1 mg of trichloroisocyanuric acid (the above-exemplified radical agent 1-1) as an organic radical generator and 5.3 mL of chloroform (containing 150 ppm of amylene as a stabilizer) as a halogenated hydrocarbon were placed. A 20 mL Schlenk flask was prepared as the reaction vessel (ii). 50 mg of N-methylaniline as an active hydrogen-containing compound, 181 mg of N,N-diisopropylethylamine (DIPEA) as an amine (neutralizer) for trapping hydrochloric acid, and 5.3 mL of chloroform (containing 150 ppm of amylene as a stabilizer) as a solvent were placed in the reaction vessel (ii). The reaction vessel (i) and the reaction vessel (ii) were connected via a 1 / 8 inch PFA tube, so that the phosgene generated in the reaction vessel (i) and described below would flow into the liquid in the reaction vessel (ii). The specific reaction method is described below.

[0052] While stirring the liquid in the reaction vessel (i) with a magnetic stirrer at room temperature (25°C), light was irradiated onto the liquid in the reaction vessel (i) from a ring-shaped 365 nm LED light source (2.4 W, manufactured by ITEC Systems Co., Ltd.), and air was introduced into the liquid in the reaction vessel (i) with an air pump via a 1 / 8 inch PFA tube. The air introduction rate was 70 mL / min. In this way, phosgene (gas) was generated in the reaction vessel (i). The generation of phosgene was confirmed with a gas detector (phosgene gas detector, manufactured by Gastec Co., Ltd.). The liquid in the reaction vessel (ii) was stirred at room temperature (25°C) with a magnetic stirrer while air containing phosgene generated in the reaction vessel (i) was bubbled through the reaction vessel. Thirty minutes after the start of the reaction, the reaction liquid in the reaction vessel (ii) was diluted with acetonitrile, and the reaction rate was examined using a high-performance liquid chromatography (Shimadzu LC-2060C). Specifically, the ratio (area%) of the peak area of ​​the target carbonyl compound to the total peak area (total of the remaining raw materials, the target carbonyl compound, and impurities) was calculated from the UV chromatogram at an absorption wavelength of 210 nm, and this was taken as the amount of carbonyl compound (%). In addition, the ratio (area%) of the peak area other than that of the remaining raw materials and the peak of the target carbonyl compound to the total peak area (total of the areas of the multiple peaks if there are multiple peaks) was taken as the amount of impurities (%). The results are shown in the table below.

[0053] [Examples 2 to 40, Comparative Examples 1 to 10] In Example 1, the preparation of the target carbonyl compound was attempted in the same manner as in Example 1, except that the type and amount of organic radical generator used, the type of halogenated hydrocarbon, the type of light source used as the external stimulus, the amount of air introduced into the reaction vessel (i), the reaction temperature, and the reaction time were as shown in the table below, and the reaction rate was examined in the same manner as above. The results are shown in the table below.

[0054] In the table below, the column "Type of organic radical generator" lists the numbers of the above-exemplified organic radical generators (numbering of the above-exemplified radical agents). The structure of the organic radical generator (radical agent) 101 used in the comparative example is as follows. "Concentration of organic radical generator (mmol / L)" is the concentration of the organic radical generator dissolved in chloroform as the halogenated hydrocarbon raw material. The temperature is the temperature of both reaction vessel (i) and reaction vessel (ii).

[0055] [ka]

[0056] [Table 1]

[0057] As shown in the above table, when the organic radical generator was an azo compound or an organic peroxide, the reaction rate was poor and a large amount of impurities were generated along with the target carbonyl compound (Comparative Examples 1 and 2). It was also confirmed that the reaction itself did not occur even if the temperature was increased when the reaction was shielded from light (Comparative Example 4). Similarly, when an inorganic radical generator was used as the radical generator, the reaction rate was poor and a large amount of impurities were generated along with the target carbonyl compound (Comparative Examples 3 and 10). It was also found that the target reaction did not occur when no radical generator was used or when an organic radical generator specified in the present invention was used, when a raw material other than halogenated hydrocarbon was used, when the reaction vessel (i) was shielded from light, or when conditions were set such that oxygen was eliminated from the atmosphere in the reaction vessel (i) (Comparative Examples 5 to 9). In contrast, it was found that when the target carbonyl compound was obtained by the production method (II) of the present invention via the production method (I) of the present invention, the target carbonyl compound was obtained with high purity (Examples 1 to 40). This means that the production method (I) of the present invention suppresses the production of by-products and produces phosgene with high efficiency, and this phosgene moves into the reaction vessel (ii) together with air with almost no by-products, resulting in the carbonylation reaction proceeding with high efficiency.

Claims

1. A method for producing a halogenated carbonyl compound, comprising generating the halogenated carbonyl compound from a mixed liquid containing an organic radical generator and a halogenated hydrocarbon by a radical reaction in the presence of oxygen. However, the organic radical generator does not include any of organic peroxides and azo compounds.

2. The method for producing a carbonyl halide compound according to claim 1, wherein the radical reaction in the presence of oxygen is a radical reaction in an air atmosphere.

3. The method for producing a carbonyl halide compound according to claim 1 , wherein the oxygen is supplied by supplying air into the mixed liquid.

4. The method for producing a carbonyl halide compound according to claim 3 , wherein the organic radical generator generates radicals by supplying light and / or heat to the mixed solution, thereby causing the radical reaction.

5. The method for producing a carbonyl halide compound according to claim 4, wherein the light is light from a light emitting diode light source.

6. The method for producing a carbonyl halide compound according to claim 4, wherein the organic radical generator comprises the following (a) and / or (b): (a) a compound that generates halogen radicals by breaking a chemical bond in response to an external stimulus; (b) A compound having a phenylcarbonyl structure.

7. The method for producing a carbonyl halide compound according to claim 6, wherein the compound (a) has a structural moiety represented by the following formula (1): *-C(=O)-N(-X)-C(=O)-* Formula (1) In the formula, X represents a halogen atom, and * represents a bond.

8. 8. The method for producing a halogenated carbonyl compound according to claim 7, wherein the halogen atom contained in the halogenated hydrocarbon is an atom selected from chlorine, bromine and iodine.

9. The method for producing a carbonyl halide compound according to claim 8, wherein the halogenated hydrocarbon is a chlorinated hydrocarbon and the carbonyl halide compound is phosgene.

10. A method for producing a carbonyl compound, comprising reacting a carbonyl compound obtained by the method for producing a carbonyl compound according to any one of claims 1 to 9 with an active hydrogen-containing compound.

11. The method for producing a carbonyl compound according to claim 10, wherein the active hydrogen-containing compound is at least one of a primary amine compound, a secondary amine compound, an alcohol compound, a thiol compound, a carboxylic acid compound, and an amino acid.

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