Method for producing nucleophilic reaction products and reactant for producing nucleophilic reaction products

Abstract

The purpose of the present invention is to provide a method for producing a nucleophilic reaction product, the method being capable of using a halogenated carbonyl compound for the reaction without requiring isolation thereof, while being able to be carried out under mild reaction conditions.　In order to achieve the above-described purpose, a method for producing a nucleophilic reaction product according to the present invention is characterized by comprising: a halogenated carbonyl compound generation step in which a halogenated carbonyl compound is generated by having a halogen oxide radical and a halogenated hydrocarbon react with each other; and a nucleophilic reaction product production step in which the halogenated carbonyl compound is reacted with a nucleophilic agent without being isolated, thereby producing a nucleophilic reaction product of the halogenated carbonyl compound and the nucleophilic agent.

Description

[Technical Field]

[0001] The present invention relates to a method for producing a nucleophilic reaction product and a reactant for producing a nucleophilic reaction product. [Background technology]

[0002] Carbonyl halide compounds are extremely important reaction raw materials in organic synthesis and are used in a variety of fields. For example, phosgene, which is a type of carbonyl halide compound, is used in the synthesis of polycarbonates and the like (Patent Document 1, etc.).

[0003] However, carbonyl halide compounds such as phosgene are unstable substances and therefore require careful handling from the viewpoint of safety, etc. Therefore, a method for producing polyureas or carbonate derivatives has been proposed, which comprises the steps of (a) irradiating chloroform or tetrachloroethane with light in the presence of oxygen to obtain a mixture containing phosgene, and (b) reacting the mixture with a primary amine having two or more amino groups in the molecule or an alcohol without isolating the phosgene (Patent Document 2). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2000-128976 [Patent Document 2] Patent No. 5900920 Summary of the Invention [Problem to be solved by the invention]

[0005] The method for producing polyureas or carbonate derivatives described in Patent Document 2 has the advantage that phosgene, which must be handled with care, can be used in the reaction without isolation. However, since chloroform and tetrachloroethane have low reactivity, obtaining phosgene from these raw materials requires a high energy and strong reaction conditions.

[0006] Therefore, an object of the present invention is to provide a method for producing a nucleophilic reaction product, which allows a carbonyl halide compound to be used in a reaction without isolation and which can be carried out under mild reaction conditions, and a reactant for producing a nucleophilic reaction product. [Means for solving the problem]

[0007] In order to achieve the above object, the method for producing a nucleophilic reaction product of the present invention comprises the steps of: a halogenated carbonyl compound generating step of reacting a halogen oxide radical with a halogenated hydrocarbon to generate a halogenated carbonyl compound; and a nucleophilic reaction product production step in which the carbonyl halide compound is reacted with a nucleophilic agent without isolation to produce a nucleophilic reaction product of the carbonyl halide compound and the nucleophilic agent.

[0008] The first reactant for producing a nucleophilic reaction product of the present invention is containing a halogen oxide radical or a halogen oxide radical generator, The halogen oxide radical is reacted with a halogenated hydrocarbon to generate a halogenated carbonyl compound, which is used in the method for producing a nucleophilic reaction product of the present invention.

[0009] The second reactant for producing a nucleophilic reaction product of the present invention is Contains halogenated hydrocarbons, The halogenated hydrocarbon is reacted with a halogen oxide radical to generate a halogenated carbonyl compound, which is used in the method for producing a nucleophilic reaction product of the present invention.

[0010] The third reactant for producing a nucleophilic reaction product of the present invention is containing a nucleophile, The method is characterized in that the nucleophilic agent is reacted with the carbonyl halide compound generated in the carbonyl halide compound generating step and used in the method for producing a nucleophilic reaction product of the present invention. [Effects of the Invention]

[0011] According to the present invention, it is possible to provide a method for producing a nucleophilic reaction product, which allows a carbonyl halide compound to be used in a reaction without isolation and which can be carried out even under mild reaction conditions, and a reactant for producing a nucleophilic reaction product. [Brief explanation of the drawings]

[0012] [Figure 1] FIG. 1 is a 13C-NMR spectrum of the deuterated chloroform solution after the reaction in Reference Example 1. [Figure 2] FIG. 2 is a spectral diagram showing the 1H-NMR spectrum of 1,2,3,4-tetrahydroquinoline and the 1H-NMR spectrum of the reaction mixture of Example 1. [Figure 3] FIG. 3 is a spectral diagram showing the 1H-NMR spectrum of 1,2,3,4-tetrahydroquinoline, the 1H-NMR spectrum of the reaction mixture in Example 2, and the 1H-NMR spectrum of the residue after separation with water in Example 2. [Figure 4] FIG. 4 is a spectral diagram showing the 1H-NMR spectrum of 1,2,3,4-tetrahydroquinoline, the 1H-NMR spectrum of the reaction mixture in Example 3, and the 1H-NMR spectrum of the residue after separation with water in Example 3. [Figure 5] FIG. 5 is a 1H-NMR spectrum diagram when compound 1b (1,2,3,4-tetrahydroisoquinoline) is reacted under condition 2 or condition 3 in Example 4. [Figure 6] FIG. 6 is a H-NMR spectrum of the compound 1c (indoline) reacted under condition 2 in Example 4. [Figure 7] FIG. 7 is a 1H-NMR spectrum diagram when compound 1d (piperidine) was reacted under condition 2 in Example 4. [Figure 8] FIG. 8 is a 1H-NMR spectrum diagram when compound 1e (pyrrolidine) was reacted under condition 2 or condition 3 in Example 4. [Figure 9] FIG. 9 is a 1H-NMR spectrum diagram when phenol (hydroxybenzene) was reacted under condition 2 in Example 5. [Figure 10] FIG. 10 is a 1H-NMR spectrum diagram when 4-chlorophenol was reacted under condition 1 in Example 5. [Figure 11] FIG. 11 is a 1H-NMR spectrum diagram when 4-nitrophenol was reacted under condition 2 in Example 5. [Figure 12] FIG. 12 is a 1H-NMR spectrum diagram when 1-propanol (n-propyl alcohol) was reacted under condition 1 in Example 5. DETAILED DESCRIPTION OF THE INVENTION

[0013] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to the following description.

[0014] In the following, the first reactant for producing a nucleophilic reaction product of the present invention, the second reactant for producing a nucleophilic reaction product of the present invention, and the third reactant for producing a nucleophilic reaction product of the present invention may be collectively referred to as the "reactant for producing a nucleophilic reaction product of the present invention."

[0015] In the method for producing a nucleophilic reaction product of the present invention, for example, in the carbonyl halide generating step, the halogen oxide radical may be activated by light irradiation.

[0016] In the method for producing a nucleophilic reaction product of the present invention, for example, in the carbonyl halide generating step, a halogen radical and singlet oxygen may be generated from the halogen oxide radical by activation by light irradiation, and the singlet oxygen may further react with the halogenated hydrocarbon to generate the carbonyl halide compound.

[0017] In the method for producing a nucleophilic reaction product of the present invention, for example, the irradiated light in the light irradiation may be visible light.

[0018] In the method for producing a nucleophilic reaction product of the present invention, for example, the halogen oxide radical may be a chlorine dioxide radical.

[0019] In the method for producing a nucleophilic reaction product of the present invention, for example, the carbonyl halide compound may be phosgene.

[0020] In the method for producing a nucleophilic reaction product of the present invention, for example, the nucleophilic reaction product may be a carbonylation product of the nucleophile.

[0021] In the method for producing a nucleophilic reaction product of the present invention, for example, the nucleophile may be at least one selected from the group consisting of amines, carboxylic acids, ammonia, alcohols, phenols, polyols, polyphenols, polyamines, formamide, urea, urea derivatives, carboxylic acid amides, aromatic compounds, α-amino acids, and thiols.

[0022] In the method for producing a nucleophilic reaction product of the present invention, for example, the nucleophilic reaction product may be at least one selected from the group consisting of amides, halogenated amides, acid halides, esters, carbonates, polycarbonates, polyurethanes, isocyanates, ureas, urea derivatives, polyureas, halogenated formates, carbamates, isocyanides, carbodiimides, cyanides, aromatic aldehydes, α-amino acid N-carboxylic anhydrides (NCAs), and thiocarbonates.

[0023] In the present invention, the "halogen" is not particularly limited, but examples thereof include fluorine, chlorine, bromine and iodine.

[0024] In the present invention, the "halogenated hydrocarbon" may be, for example, a compound in which all or part of the hydrogen atoms in a hydrocarbon have been substituted with halogen atoms.

[0025] In the present invention, the chain compound (e.g., alkane, unsaturated aliphatic hydrocarbon, etc.) or the chain substituent derived from the chain compound (e.g., hydrocarbon group such as alkyl group, alkylene group, unsaturated aliphatic hydrocarbon group, etc.) may be, for example, linear or branched, and the number of carbon atoms therein is not particularly limited and may be, for example, 1 to 40, 1 to 32, 1 to 24, 1 to 18, 1 to 12, 1 to 6, or 1 to 2; and in the case of an unsaturated hydrocarbon group, the number of carbon atoms therein may be, for example, 2 to 40, 2 to 32, 2 to 24, 2 to 18, 2 to 12, or 2 to 6. In the present invention, the number of ring members (the number of atoms constituting the ring) of a cyclic compound (e.g., a cyclic saturated hydrocarbon, a non-aromatic cyclic unsaturated hydrocarbon, an aromatic hydrocarbon, a heteroaromatic compound, etc.) or a cyclic group derived from a cyclic compound (e.g., a cyclic saturated hydrocarbon group, a non-aromatic cyclic unsaturated hydrocarbon group, an aryl group, an arylene group, a heteroaryl group, a heteroarylene group, etc.) is not particularly limited, and may be, for example, 5 to 32, 5 to 24, 6 to 18, 6 to 12, or 6 to 10. Furthermore, when isomers exist in a substituent or the like, for example, the type of isomer is not particularly limited, and as a specific example, when simply referring to a "naphthyl group," it may be, for example, a 1-naphthyl group or a 2-naphthyl group.

[0026] In the present invention, the term "salt" is not particularly limited and may be, for example, an acid addition salt or a base addition salt. The acid that forms the acid addition salt may be, for example, an inorganic acid or an organic acid, and the base that forms the base addition salt may be, for example, an inorganic base or an organic base. The inorganic acid is not particularly limited and examples thereof include sulfuric acid, phosphoric acid, hydrofluoric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, hypofluorite acid, hypochlorous acid, hypobromous acid, hypoiodous acid, fluorite acid, chlorous acid, bromous acid, iodous acid, fluoric acid, chloric acid, bromic acid, iodic acid, perfluoric acid, perchloric acid, perbromic acid, and periodic acid. The organic acid is not particularly limited and examples thereof include p-toluenesulfonic acid, methanesulfonic acid, oxalic acid, p-bromobenzenesulfonic acid, carbonic acid, succinic acid, citric acid, benzoic acid, and acetic acid. The inorganic base is not particularly limited, and examples thereof include ammonium hydroxide, alkali metal hydroxides, alkaline earth metal hydroxides, carbonates, and hydrogen carbonates, and more specific examples thereof include sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, calcium hydroxide, and calcium carbonate. The organic base is not particularly limited, and examples thereof include ethanolamine, triethylamine, and tris(hydroxymethyl)aminomethane.

[0027] Hereinafter, the embodiments of the present invention will be described in more detail with reference to examples, but the present invention is not limited to the following embodiments.

[0028] [1. Method for producing nucleophilic reaction products] As described above, the method for producing a nucleophilic reaction product of the present invention is characterized by comprising a carbonyl halide compound generation step of reacting a halogen oxide radical with a halogenated hydrocarbon to generate a carbonyl halide compound, and a nucleophilic reaction product production step of reacting the carbonyl halide compound with a nucleophile without isolating it to produce a nucleophilic reaction product of the carbonyl halide compound and the nucleophile. The method for producing a nucleophilic reaction product of the present invention will be described in more detail below with examples.

[0029] [1-1. Carbonyl halide compound generation process] In the halogenated carbonyl compound generating step, as described above, a halogen oxide radical is reacted with a halogenated hydrocarbon to generate a halogenated carbonyl compound. The halogenated carbonyl compound generating step may be carried out in a reaction system different from that in the nucleophilic reaction product producing step, or may be carried out in the same reaction system as that in the nucleophilic reaction product producing step.

[0030] [1-1-1. Halogen oxide radicals] The halogen oxide radical is not particularly limited, but may be, for example, FO · (oxygen difluoride radical), F2O2 · (dioxygen difluoride radical), ClO2 · (chlorine dioxide radical), BrO2 · (bromine dioxide radical), I2O5 · Examples of the halogen oxide radical include halogen oxide radicals such as iodine (V) oxide. The halogen oxide radicals may be, for example, any one of the above, or two or more of the above may be used in combination.

[0031] The method for obtaining the halogen oxide radicals is not particularly limited. For example, the halogen oxide radicals may be generated from a source of the halogen oxide radicals (hereinafter, sometimes referred to as a "radical generating source" or simply as a "generation source"). The present invention may further include, for example, a halogen oxide radical generating step of generating the halogen oxide radicals from the radical generating source. The halogen oxide radical generating step may be carried out, for example, prior to the carbonyl halide compound generating step or simultaneously with the carbonyl halide compound generating step. Furthermore, the halogen oxide radical generating step may be carried out, for example, in a reaction system different from that of the carbonyl halide compound generating step, or may be carried out in the same reaction system as that of the carbonyl halide compound generating step.

[0032] The radical generating source is not particularly limited and can be appropriately selected depending on, for example, the type of the halogen oxide radical. The halogen oxide radical generating source may be, for example, one type, or a combination of two or more types.

[0033] The radical source is, for example, a compound containing oxygen and a halogen, and specific examples include, for example, a halous acid (HXO2) or a salt thereof. The salt of the halous acid is not particularly limited, and examples thereof include metal salts, and examples of the metal salts include alkali metal salts, alkaline earth metal salts, and rare earth salts. The halogen oxide radical source may be, for example, a compound containing oxygen, a halogen, and a Group 1 element (e.g., at least one selected from the group consisting of H, Li, Na, K, Rb, and Cs), and examples thereof include, for example, a halous acid or an alkali metal salt thereof. When the halogen oxide radical is the chlorine dioxide radical, its generating source is not particularly limited and may be, for example, chlorous acid (HClO) or a salt thereof. Specific examples include sodium chlorite (NaClO), lithium chlorite (LiClO), potassium chlorite (KClO), magnesium chlorite (Mg(ClO)), calcium chlorite (Ca(ClO)). Among these, sodium chlorite (NaClO) is preferred from the viewpoints of cost, ease of handling, etc. For example, the same method can be adopted for other halogen oxide radical generating sources. Other halogen oxide radical generating sources include, for example, bromates such as sodium bromite, and iodates such as sodium iodite.

[0034] The reaction system in the halogen oxide radical generating step may be, for example, a gas phase, a liquid phase, a solid phase, or a two-phase system of a gas phase and a liquid phase. The liquid phase may be, for example, an aqueous phase, an organic phase, a two-phase system of an aqueous phase and an organic phase, or a mixed phase of water and an organic solvent. An example of using an aqueous phase in the reaction system is dissolving the radical generating source (e.g., a halous acid or a salt thereof, such as sodium chlorite) in water together with an acid (e.g., hydrochloric acid) to form an acidic aqueous solution, from which a halogen oxide radical (e.g., chlorine dioxide gas) can be generated. This halogen oxide radical can be activated, for example, by irradiation with light, and used in the subsequent carbonyl halide compound generating step.

[0035] In the halogen oxide radical generating step, the reaction system may or may not be irradiated with light. In the present invention, "not irradiating with light" the reaction system includes, but is not limited to, shading the reaction system to prevent light from entering the reaction system. In the present invention, "not irradiating with light" the reaction system may or may not include shading the reaction system to prevent light from entering the reaction system. In the present invention, "not irradiating with light" the reaction system may mean, for example, a state in which natural light, room light, or the like is incident on the reaction system without active light irradiation using a light source or the like. For example, by not irradiating the reaction system with light, the reaction can be carried out simply and at low cost.

[0036] In the aqueous phase, the concentration of the source is not particularly limited. When the source is the compound, the concentration, when converted into the halogen oxide ion concentration, is, for example, 0.0001 mol / L or more at the lower limit and 1 mol / L or less at the upper limit. When the concentration, when converted into the number of moles of the halogen oxide ions, is, for example, 1 / 100,000 times or more and 1,000 times or less of the number of moles of the raw material. When the source is a halogen acid or halogen acid salt (e.g., chlorous acid or halogen acid salt), the concentration is, for example, 1 / 100,000 times or more of the number of moles of the raw material, and 1,000 times or less of the number of moles of the raw material. -When converted into a concentration of halous acid ions (e.g., chlorous acid ions (ClO2)), for example, the lower limit is 0.0001 mol / L or more and the upper limit is 1 mol / L or less. - When converted to the number of moles of the raw material, for example, the lower limit is 1 / 100,000 times or more the number of moles of the raw material, and the upper limit is 1,000 times or less. For other sources, for example, the above concentrations can also be applied.

[0037] The aqueous phase may further contain at least one of a Lewis acid and a Bronsted acid, which may be reacted with the halogen oxide ions to generate the halogen oxide radicals. The at least one of the Lewis acid and the Bronsted acid may be, for example, at least one of a Lewis acid and a Bronsted acid containing a Group 1 element. The halogen oxide ions may be, for example, chlorite ions (ClO2 - ) The aqueous phase may contain, for example, only one of the Lewis acid and the Bronsted acid, or both, or one substance may serve as both the Lewis acid and the Bronsted acid. Only one type of Lewis acid or one type of Bronsted acid may be used, or multiple types may be used in combination. In the present invention, the "Lewis acid" refers to, for example, a substance that acts as a Lewis acid with respect to the source of generation of the halogen oxide radical.

[0038] The concentration of at least one of the Lewis acid and the Bronsted acid in the aqueous phase is not particularly limited and can be appropriately set depending on, for example, the type of the polymer to be modified, etc. The lower limit of the concentration is, for example, 0.0001 mol / L or more and the upper limit is 1 mol / L or less.

[0039] The Bronsted acid is not particularly limited and may be, for example, an inorganic acid or an organic acid, and specific examples include trifluoromethanesulfonic acid, trifluoroacetic acid, acetic acid, hydrofluoric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, sulfurous acid, nitric acid, nitrous acid, phosphoric acid, and phosphorous acid. ais, for example, 10 or less. a The lower limit of is not particularly limited, and is, for example, −10 or more.

[0040] The aqueous phase preferably contains, for example, the halogen oxide ion and the Bronsted acid, and is, for example, an aqueous phase in which the compound and the Bronsted acid (e.g., hydrochloric acid) are dissolved in an aqueous solvent. As a specific example, when the halogen oxide radical is a chlorine dioxide radical, the aqueous phase preferably contains, for example, chlorite ion (ClO - ) and a Bronsted acid, for example, an aqueous phase in which the sodium chlorite (NaClO2) and the Bronsted acid (for example, hydrochloric acid) are dissolved in an aqueous solvent is preferred.

[0041] In the aqueous phase, for example, the Lewis acid, the Bronsted acid, the radical generating source, etc. may be dissolved or insoluble in the aqueous solvent. In the latter case, they may be dispersed or precipitated in the aqueous solvent.

[0042] The halogen oxide radical generating step is not particularly limited, and for example, by adding a source of the halogen oxide radical to the aqueous solvent, the halogen oxide radical (e.g., chlorine dioxide radical) can be spontaneously generated from the halogen oxide ion (e.g., chlorite ion). The aqueous phase preferably contains, for example, the source dissolved in the aqueous solvent, and is preferably allowed to stand. In the halogen oxide radical generating step, the generation of the halogen oxide radical can be further promoted by, for example, further allowing at least one of the Lewis acid and the Bronsted acid to coexist in the aqueous phase. In the halogen oxide radical generating step, the halogen oxide radical can be generated by, for example, irradiating the aqueous phase with light, as described above. However, the halogen oxide radical can also be generated without light irradiation, for example, by simply allowing the aqueous phase to stand.

[0043] The halogen oxide radical generating step may also be carried out in the same manner as or in accordance with the methods described in, for example, WO2018 / 110710A1, WO2019 / 221299A1, WO2019 / 221300A1, etc.

[0044] [1-1-2. Halogenated hydrocarbons and halogenated carbonyl compounds] The halogenated hydrocarbon may be, for example, a compound in which all or some of the hydrogen atoms of a hydrocarbon have been substituted with halogen atoms, as described above. The halogenated hydrocarbon is not particularly limited, and for example, one type may be used alone or multiple types may be used in combination. The hydrocarbon is not particularly limited, and may be, for example, a linear or branched alkane, an unsaturated aliphatic hydrocarbon, a cyclic saturated hydrocarbon, a non-aromatic cyclic unsaturated hydrocarbon, an aromatic hydrocarbon, or the like. Examples of the hydrocarbon include methane, ethane, propane, n-butane, 2-methylpropane, cyclopropane, cyclobutane, cyclopentane, cyclohexane, cyclopentene, cyclohexene, benzene, toluene, xylene, etc. Examples of the halogenated hydrocarbons include monohalomethanes (CH3X), dihalomethanes (CH2X2), trihalomethanes (CHX3), tetrahalomethanes (CX4), monohaloethanes (C2H5X1), dihaloethanes (C2H4X2), trihaloethanes (C2H3X3), tetrahaloethanes (C2H2X4) (X is a halogen atom), etc. More specific examples of the halogenated hydrocarbons 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), tetrachlorom ... Examples of halogenated carbonyl compounds include ethane (C2H2Cl4), 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 (CHI), diiodomethane (CHI2), triiodomethane (CHI3, also known as iodoform), etc. According to the present invention, for example, a halogenated hydrocarbon (e.g., chloroform) that is inexpensive and easily available can be used to generate a halogenated carbonyl compound (e.g., phosgene), which allows the reaction to be carried out at low cost and on a large scale.

[0045] The carbonyl halide compound generated in the carbonyl halide compound generation step is not particularly limited, and examples thereof 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. In the carbonyl halide compound generation step, the halogenated hydrocarbon used as the raw material for the carbonyl halide compound can be appropriately selected depending on the type of the target carbonyl halide compound. From the viewpoints of reaction efficiency, convenience, cost, and the like, it is particularly preferable that the halogenated hydrocarbon is a chlorinated hydrocarbon and the carbonyl halide compound is phosgene.

[0046] [1-1-3. Reaction conditions for the carbonyl halide compound generation process] The reaction conditions for the carbonyl halide compound generating step are not particularly limited, but the step can be carried out, for example, under the following reaction conditions.

[0047] First, the reaction system in the carbonyl halide compound generating step may be, for example, a gas phase, a liquid phase, a solid phase, or a two-phase system of a gas phase and a liquid phase. The liquid phase may be, for example, an aqueous phase, an organic phase, a two-phase system of an aqueous phase and an organic phase, or a mixed phase of water and an organic solvent.

[0048] From the viewpoints of reaction efficiency, convenience, etc., it is preferable to react a halogen oxide radical with a halogenated hydrocarbon in a liquid phase. In this case, for example, a solvent other than the halogenated hydrocarbon may be used, but from the viewpoints of reaction efficiency, convenience, etc., it is preferable to use the halogenated hydrocarbon itself as the solvent.

[0049] The method for reacting the halogen oxide radical with the halogenated hydrocarbon in a liquid phase is not particularly limited. For example, the halogen oxide radical may be introduced into a liquid phase containing the halogenated hydrocarbon. The liquid phase containing the halogenated hydrocarbon may be, for example, the halogenated hydrocarbon itself in liquid form. The method for introducing the halogen oxide radical into the liquid phase is not particularly limited. For example, when the halogen oxide radical is gaseous, the halogen oxide radical may be brought into contact with the liquid phase or blown into the liquid phase. The halogen oxide radical may be, for example, the halogen oxide radical generated in the halogen oxide radical generating step. In this case, for example, the reaction system in the halogen oxide radical generating step may be an aqueous phase, and the reaction system in the carbonyl halide compound generating step may be an organic phase. In this case, the method for introducing the halogen oxide radical generated from the aqueous phase into the organic phase is not particularly limited. For example, the aqueous phase and the organic phase may be directly contacted. In this case, the aqueous phase and the organic phase may be appropriately stirred, etc. Alternatively, the gaseous halogen oxide radicals generated from the aqueous phase may be made to be mobile into the organic phase via the gas phase. In this case, for example, the organic phase may be appropriately stirred to increase the efficiency of introducing the halogen oxide radicals into the organic phase. In this case, for example, an H-shaped tube may be used as a reaction tool or reactor, as described in the examples below. Furthermore, for example, when the reaction is carried out on a larger scale, other suitable reaction tools or reactors may be used.

[0050] The concentration of the halogen oxide radicals in the reaction system in the carbonyl halide compound generating step is not particularly limited. For example, when the reaction system is in a liquid phase, the concentration of the halogen oxide radicals may be, for example, 0.0001 mol / L or more, 0.001 mol / L or more, 0.01 mol / L or more, 0.1 mol / L or more, or 1.0 mol / L or more, or may be, for example, 10 mol / L or less, 1.0 mol / L or less, 0.1 mol / L or less, 0.01 mol / L or less, or 0.001 mol / L or less. The concentration of the halogen oxide radicals may be, for example, 0.001 to 10 mol / L, 0.01 to 1 mol / L, or 0.02 to 0.5 mol / L.

[0051] Furthermore, for example, as described below, the nucleophilic agent may be present in the reaction system of the carbonyl halide compound generation step, and the nucleophilic reaction product production step may be carried out in the same reaction system as the carbonyl halide compound generation step.

[0052] In the carbonyl halide compound generating step, as described above, the halogenated hydrocarbon itself may be used as the solvent, but a solvent other than the halogenated hydrocarbon may also be used. For example, when the nucleophilic reaction product producing step is carried out in the same reaction system as the carbonyl halide compound generating step, the other solvent may be used to facilitate dissolution of the nucleophile.

[0053] The other solvent is not particularly limited and may be water, an organic solvent, or a mixed solvent of water and an organic solvent. The organic solvent is not particularly limited. For example, only one type of organic solvent may be used, or multiple types may be used in combination. In the present invention, examples of the organic solvent include hydrocarbons (e.g., pentane, hexane, cyclohexane, etc.), nitriles (e.g., acetonitrile, etc.), esters (e.g., ethyl acetate, etc.), alcohols (e.g., methanol, ethanol, 2-propanol, etc.), ketones (e.g., acetone, etc.), ethers (e.g., diethyl ether, THF (tetrahydrofuran), etc.), amides (e.g., DMF (dimethylformamide), DMA (dimethylacetamide), NMP (N-methyl-2-pyrrolidone), etc.), sulfoxides (e.g., DMSO (dimethyl sulfoxide), etc.), halogenated solvents, and fluorous solvents.

[0054] A "halogenated solvent" refers to, for example, a solvent in which all or most of the hydrogen atoms of a hydrocarbon have been substituted with halogen. The halogenated solvent may be, for example, a solvent in which 50% or more, 60% or more, 70% or more, 80% or more, or 90% or more of the number of hydrogen atoms of the hydrocarbon have been substituted with halogen. The halogenated solvent is not particularly limited, and examples thereof include methylene chloride, chloroform, carbon tetrachloride, carbon tetrabromide, and the fluorous solvents described below.

[0055] A "fluorous solvent" is a type of halogenated solvent, and refers to, for example, a solvent in which all or most of the hydrogen atoms of a hydrocarbon have been substituted with fluorine atoms. The fluorous solvent may be, for example, a solvent in which 50% or more, 60% or more, 70% or more, 80% or more, or 90% or more of the number of hydrogen atoms of the hydrocarbon have been substituted with fluorine atoms. In the present invention, the use of the fluorous solvent has the advantage that, for example, the reactivity of the solvent itself is low, thereby making it possible to further suppress or prevent side reactions.

[0056] Examples of the fluorous solvent include solvents represented by the following chemical formulas (F1) to (F6), and among these, for example, CF3(CF2)4CF3 in which n=4 in the following chemical formula (F1) is preferred.

[0057] [ka]

[0058] The boiling point of the organic solvent is not particularly limited. The organic solvent can be appropriately selected depending on, for example, the temperature conditions of the carbonyl halide compound generating step. When the reaction temperature in the carbonyl halide compound generating step is set to a high temperature, a high-boiling point solvent can be selected as the organic solvent. Note that, as will be described later, the present invention does not require heating and can be carried out, for example, at room temperature and atmospheric pressure. In such cases, the organic solvent does not need to be a high-boiling point solvent, and from the viewpoint of ease of handling, a solvent with a not-so-high boiling point can be used.

[0059] When using the other solvent, the concentration of the halogenated hydrocarbon in the reaction system in the carbonyl halide compound generating step is not particularly limited. For example, when the reaction system is in a liquid phase, the concentration of the halogenated hydrocarbon may be, for example, 0.0001 mol / L or more, 0.001 mol / L or more, 0.01 mol / L or more, 0.1 mol / L or more, or 1.0 mol / L or more, or may be, for example, 10 mol / L or less, 1.0 mol / L or less, or 0.1 mol / L or less. The concentration of the halogenated hydrocarbon may be, for example, 0.001 to 10 mol / L, 0.01 to 1.0 mol / L, or 0.02 to 0.5 mol / L.

[0060] In the carbonyl halide compound generating step, the reaction system may or may not be irradiated with light. For example, irradiating the reaction system with light can improve the reaction efficiency between the halogen oxide radical and the halogenated hydrocarbon. Specifically, for example, as described above, in the carbonyl halide generating step, the halogen oxide radical may be activated by being irradiated with light. More specifically, for example, as described above, in the carbonyl halide generating step, a halogen radical and singlet oxygen may be generated from the halogen oxide radical by activation through the irradiation with light, and the singlet oxygen may then react with the halogenated hydrocarbon to generate the carbonyl halide compound. For example, when the halogen oxide radical is a chlorine dioxide radical and the halogenated hydrocarbon is chloroform, a reaction such as that shown in Scheme 1 below is thought to occur. In Scheme 1 below, chlorine dioxide gas (chlorine dioxide radical) is activated by irradiation with light to generate a chlorine radical and singlet oxygen, and the singlet oxygen reacts with chloroform to generate phosgene. However, the following Scheme 1 is merely an example of a possible reaction mechanism, and the present invention is not limited thereto.

[0061] [ka]

[0062] The conditions for the light irradiation are not particularly limited. The wavelength of the irradiation light is not particularly limited, but the lower limit may be, for example, 200 nm or more, 300 nm or more, or 400 nm or more, and the upper limit may be, for example, 800 nm or less, 700 nm or less, 600 nm or less, or 500 nm or less. The wavelength may be, for example, 200 to 800 nm, 300 to 700 nm, 400 to 600 nm, or 400 to 500 nm. The irradiation light may be, for example, ultraviolet light, visible light, or infrared light. From the perspective of comprehensive consideration of convenience, safety, reaction efficiency, etc., visible light is preferred. The light irradiation time is not particularly limited, but the lower limit may be, for example, 1 second or more, and the upper limit is not particularly limited, but may be, for example, 1,000 hours or less.

[0063] The reaction temperature in the carbonyl halide compound generating step is not particularly limited, and the lower limit is, for example, -20°C or higher, and the upper limit is, for example, 100°C or lower or 40°C or lower, and the range is, for example, 0 to 100°C or 0 to 40°C. The atmospheric pressure during the reaction is not particularly limited, and the lower limit is, for example, 0.1 MPa or higher, and the upper limit is, for example, 100 MPa or lower, 10 MPa or lower, or 0.5 MPa or lower, and the range is, for example, 0.1 to 100 MPa, 0.1 to 10 MPa, or 0.1 to 0.5 MPa. Examples of reaction conditions for the carbonyl halide compound generating step include a temperature of 0 to 100°C or 0 to 40°C and a pressure of 0.1 to 0.5 MPa. As described above, in the carbonyl halide compound generating step, the reaction system may or may not be irradiated with light. According to the method for producing a nucleophilic reaction product of the present invention, the carbonyl halide compound generating step or all of the steps including it can be carried out at room temperature (room temperature) and normal pressure (atmospheric pressure) without heating, pressurizing, decompressing, etc. "Room temperature" is not particularly limited and is, for example, 5 to 35°C. Furthermore, according to the present invention, the carbonyl halide compound generating step or all of the steps including it can be carried out in the atmosphere without, for example, replacing with an inert gas.

[0064] The light source for the light irradiation is not particularly limited, and for example, visible light contained in natural light such as sunlight can be used. The use of natural light allows, for example, easy excitation. Furthermore, as the light source, for example, a xenon lamp, a halogen lamp, a fluorescent lamp, a mercury lamp, an LED lamp, or the like can be used instead of or in addition to the natural light. From the viewpoints of light absorption efficiency of chlorine dioxide and power saving, an LED lamp is preferred, and an LED lamp of 365 nm or 405 nm is more preferred. In the light irradiation, for example, a filter that cuts wavelengths other than the required wavelength can also be used as appropriate.

[0065] [1-2. Nucleophilic reaction product manufacturing process] In the method for producing a nucleophilic reaction product of the present invention, the nucleophilic reaction product production step may be carried out after the carbonyl halide compound generation step, or may be carried out simultaneously with the carbonyl halide compound generation step.

[0066] The nucleophilic reaction product production step may be carried out in the same reaction system as the reaction system of the carbonyl halide compound generation step, or in a different reaction system. In the method for producing a nucleophilic reaction product of the present invention, the carbonyl halide compound is reacted with a nucleophile without isolation. Therefore, from the viewpoint of convenience, it is preferable to carry out the nucleophilic reaction product production step in the same reaction system as the carbonyl halide compound generation step. Specifically, for example, the nucleophile may be previously coexisted in the reaction system of the carbonyl halide compound generation step, and the nucleophilic reaction product production step and the carbonyl halide compound generation step may be carried out in this same reaction system. More specifically, for example, the halogenated hydrocarbon and the nucleophile may be previously dissolved or dispersed in a solvent, and the nucleophilic reaction product production step and the carbonyl halide compound generation step may be carried out in this solvent.

[0067] The concentration of the nucleophilic agent in the reaction system in the nucleophilic reaction product production step is not particularly limited. For example, when the reaction system is in a liquid phase, the concentration of the nucleophilic agent may be, for example, 0.0001 mol / L or more, 0.001 mol / L or more, 0.01 mol / L or more, 0.1 mol / L or more, or 1.0 mol / L or more, or may be, for example, 50 mol / L or less, 10 mol / L or less, 5.0 mol / L or less, 1.0 mol / L or less, or 0.1 mol / L or less. The concentration of the nucleophilic agent may be, for example, 0.0001 to 50 mol / L, 0.01 to 10 mol / L, or 0.1 to 1.0 mol / L.

[0068] In the nucleophilic reaction product production step, reaction conditions such as reaction temperature and reaction time are not particularly limited, and may be the same as or equivalent to the reaction conditions in a general reaction between a nucleophile and a carbonyl halide compound, or may be appropriately set with reference to such conditions. Furthermore, for example, when the nucleophilic reaction product production step and the carbonyl halide compound generation step are carried out simultaneously in the same reaction system, the reaction conditions in the nucleophilic reaction product production step may be the same as those in the carbonyl halide compound generation step. Furthermore, in the nucleophilic reaction product production step, the reaction system may or may not be irradiated with light. The conditions for light irradiation are not particularly limited, and may be the same as those in the carbonyl halide compound generation step, for example.

[0069] In the nucleophilic reaction product production process, the term "nucleophile" refers to a substance that easily reacts with or attacks a low-electron-density portion of a molecule (the carbonyl halide compound in this invention) that is the target of the reaction. In the carbonyl halide compound, the low-electron-density portion is specifically the carbonyl carbon. The nucleophile is preferably a substance that contains a high-electron-density portion, and may be, for example, a Brønsted base (i.e., electron pair donor), anion, aliphatic amine, aromatic amine (e.g., aniline, etc.), hydrazine, diamine, polyamine, ammonia, alcohol, phenol, diol, polyol, polyphenol, aminoalcohol, aromatic compound, amino acid, thiol, or the like.

[0070] In the nucleophilic reaction product production process, the nucleophilic agent as a raw material and the nucleophilic reaction product as a product are not particularly limited and may be the same as or equivalent to a general reaction between a nucleophile and a carbonyl halide compound, for example. That is, the method for producing a nucleophilic reaction product of the present invention is applicable to a wide variety of nucleophiles, similar to a general reaction between a nucleophile and a carbonyl halide compound, and thereby, a variety of nucleophilic reaction products can be produced. The nucleophilic agent as a raw material may be, for example, an organic compound or an inorganic substance. Furthermore, only one type of nucleophile may be used, or two or more types may be used in combination. As mentioned above, the nucleophilic reaction product is not particularly limited, and examples thereof include acid halides (e.g., acid fluorides, acid chlorides, acid bromides, or acid iodides), amides, esters, carbonates, polycarbonates, polyurethanes, isocyanates, ureas, polyureas, urea derivatives, halogenated formates (e.g., fluoroformates, chloroformates, bromoformates, or iodoformates), carbonates, carbamates, isocyanides, carbodiimides, cyanides, aldehydes (e.g., aromatic aldehydes), α-amino acid N-carboxylic anhydrides (NCAs), etc. The structures of these nucleophilic reaction products and the corresponding raw materials (nucleophiles) are not particularly limited, and can be represented, for example, by the chemical formulas shown in Scheme I below. The following Scheme I is a reprint of a diagram (chemical formula) published in the presentation materials (presenter: Tsuda Akihiko, https: / / shingi.jst.go.jp / var / rev0 / 0000 / 9540 / 2019_kobe-u_1.pdf [search date: February 19, 2021]) at the Kobe University New Technology Briefing [sponsored by: Japan Science and Technology Agency, National Research and Development Agency, Kobe University, held on August 1, 2019], and has been given the title "Scheme I" by the applicant of the present application. Furthermore, in the present invention, instead of or in addition to the phosgene in the following Scheme I, a carbonyl halide compound other than phosgene may be used.

[0071] [ka]

[0072] In the present invention, R and R in Scheme I 1 and R 2 are not particularly limited and may be any atom or atomic group. 1 and R 2 The structure of R and R in Scheme I may be the same as or similar to that of the nucleophilic agent or the nucleophilic reaction product in a general reaction in which a nucleophilic agent reacts with a carbonyl halide compound to produce a nucleophilic reaction product. 1 and R 2 is a monovalent group, the R, R 1 and R 2 For example, each of R and R in Scheme I may independently represent a hydrogen atom, a hydroxyl group, a mercapto group (thiol group), a carboxyl group, an amino group, or a chain substituent (e.g., a hydrocarbon group such as an alkyl group or an unsaturated aliphatic hydrocarbon group), or may represent a cyclic group (e.g., a cyclic saturated hydrocarbon group, a non-aromatic cyclic unsaturated hydrocarbon group, an aryl group, a heteroaryl group, etc.), and may be substituted or unsubstituted with other substituents. 1 and R 2 is a divalent group (crosslinked chain), the R, R 1 and R 2 may each independently be, for example, an ether bond (-O-), an ester bond (-COO-), a carbonate bond (-OCOO-), a carbamate bond (-NCOO-), a urea bond (-NCON-), or a chain substituent (e.g., a hydrocarbon group such as an alkylene group or an unsaturated aliphatic hydrocarbon group), or may be a cyclic group (e.g., a cyclic saturated hydrocarbon group, a non-aromatic cyclic unsaturated hydrocarbon group, an arylene group, a heteroarylene group, etc.), which may or may not be substituted with other substituents. Furthermore, Ar in Scheme I is not particularly limited, and may be, for example, an aromatic compound (e.g., an aromatic hydrocarbon, a heteroaromatic compound, etc.) or a group derived from an aromatic compound (e.g., an aryl group, a heteroaryl group, etc.).

[0073] Furthermore, in the present invention, in the nucleophilic reaction product production process, the nucleophilic agent as a raw material and the nucleophilic reaction product as a product are not limited to the substances shown in Scheme I. For example, the nucleophilic agent may be a thiol, and the nucleophilic reaction product may be a thiocarbonate. Also, for example, the nucleophilic agent may be ammonia or an amine, and the nucleophilic reaction product may be a halogenated amide (X-CO-NR 1 R 2 , where X is a halogen, CO is a carbonyl group, and R 1 and R 2 is the same as in Scheme I. Other examples of the nucleophilic agent include imidazole, phosphonate ester, lactam, imine, hydrazine, pyrrole, triazole, and indole, and examples of the nucleophilic reaction product include carbonyldiimidazole, halogenated phosphate ester (e.g., chlorophosphate ester), imide halide (e.g., imide chloride), and acid halide (e.g., formic acid chloride).

[0074] In the nucleophilic reaction product production step, the combination of the nucleophilic agent as a raw material and the nucleophilic reaction product as a product is not particularly limited, and examples thereof include the combinations shown in Table 1 below. Note that in Table 1 below, when there are two or more types of nucleophilic reaction products as products for a nucleophilic agent as a raw material, the nucleophilic reaction products may be any one type or any two or more types.

[0075] [Table 1]

[0076] The purification method, isolation method, etc. of the nucleophilic reaction product produced in the nucleophilic reaction product production step are not particularly limited, and for example, methods similar to those used in general chemical reactions may be used as appropriate. Specifically, for example, methods such as liquid separation, recrystallization, distillation, column chromatography, etc. may be used as appropriate as needed. Furthermore, for example, prior to or simultaneously with the purification method, isolation, etc. of the nucleophilic reaction product, water, methanol, ethanol, phenol, amine, etc. may be added as appropriate to react and consume all of the unreacted carbonyl halide compound. In this way, for example, post-treatment of the nucleophilic reaction product production step can be performed safely without releasing the carbonyl halide compound outside the reaction system.

[0077] Furthermore, the method for producing a nucleophilic reaction product of the present invention may or may not include other steps in addition to the carbonyl halide compound generating step and the nucleophilic reaction product producing step. The other steps may or may not include, for example, the halogen oxide radical generating step, or may or may not include steps other than the halogen oxide radical generating step.

[0078] [2. Reactants for producing nucleophilic reaction products] As described above, the reactant for producing a nucleophilic reaction product of the present invention includes the first reactant for producing a nucleophilic reaction product of the present invention, the second reactant for producing a nucleophilic reaction product of the present invention, and the third reactant for producing a nucleophilic reaction product of the present invention. The characteristics of each are as described above. That is, the reactant for producing a nucleophilic reaction product of the present invention contains a halogen oxide radical or a halogen oxide radical generator, a halogenated hydrocarbon, or a nucleophile. The chemical structures of the halogen oxide radical, the halogen oxide radical generator, the halogenated hydrocarbon, and the nucleophile are not particularly limited, but are as described, for example, in "1. Method for producing a nucleophilic reaction product" above.

[0079] [3. Uses of the present invention] As described above, the method for producing a nucleophilic reaction product of the present invention is applicable to a wide variety of nucleophiles, similar to the general reaction between a nucleophile and a carbonyl halide compound, thereby enabling the production of a variety of nucleophilic reaction products. Therefore, the method for producing a nucleophilic reaction product of the present invention is applicable to a very wide range of fields. For example, carbamoyl chloride is an important intermediate in pharmaceuticals, fine chemicals, and resin synthesis. According to the method for producing a nucleophilic reaction product of the present invention, for example, an amine or imine can be used as the nucleophile and reacted with a carbonyl halide compound (e.g., phosgene) to produce the nucleophilic reaction product, carbamoyl chloride. Other industrial fields to which the present invention can be applied include, for example, the polycarbonate industry, the carbamate-related industry, pesticides, dyes, perfumes, pharmaceuticals, and isocyanate production.

[0080] Furthermore, as described above, the method for producing a nucleophilic reaction product of the present invention allows the carbonyl halide compound to be used in the reaction without isolation, and therefore has advantages such as high safety, shortening of the work steps, and reduction of costs.

[0081] Furthermore, as described above, the method for producing a nucleophilic reaction product of the present invention can be carried out under mild reaction conditions. Therefore, for example, a nucleophilic reaction product can be produced by applying the method for producing a nucleophilic reaction product of the present invention to raw materials that have been difficult to use in conventional reactions. Specifically, for example, when light is irradiated in the method for producing a nucleophilic reaction product of the present invention, the irradiated light is not particularly limited, as described above, and may be, for example, ultraviolet light, visible light, or infrared light. For example, while conventional reactions require ultraviolet irradiation, if the method for producing a nucleophilic reaction product of the present invention can perform the reaction with visible light irradiation, it would be possible to improve convenience, safety, substrate applicability, reaction time, reaction efficiency, productivity, and the like. Specifically, for example, in conventional reactions, ultraviolet light is required as excitation light to directly photoexcite chloroform to generate phosgene. However, according to the present invention, for example, instead of directly photoexciting chloroform, phosgene can also be generated by activating chlorine dioxide radicals with visible light and reacting them with chloroform, as described above. Furthermore, for example, reactions that require ultraviolet irradiation are difficult to apply to raw materials that easily absorb ultraviolet light (i.e., are easily decomposed by ultraviolet irradiation), such as aromatic compounds. If such raw materials can be reacted with visible light by the method for producing a nucleophilic reaction product of the present invention, the range of raw materials (nucleophiles) that can be used to produce nucleophilic reaction products will be dramatically expanded. [Example]

[0082] Examples of the present invention will be described below, but the present invention is not limited to the following examples.

[0083] In the present example, NMR (nuclear magnetic resonance) spectra were measured using ECS400 (trade name) manufactured by JEOL.

[0084] [Reference example 1] In this reference example, it was confirmed that phosgene (carbonyl halide) was generated in the reaction system by reacting chlorine dioxide radicals (halogen oxide radicals) with chloroform (halogenated hydrocarbon). More specifically, phosgene was generated by reacting chlorine dioxide radicals with deuterated chloroform according to the following scheme E1.

[0085] [ka]

[0086] The reaction of Scheme E1 was carried out as follows. First, 113 mg (0.8 mmol) of sodium chlorite, 5.7 mL of water, and 57 μL of 35% hydrochloric acid were mixed and allowed to stand at room temperature for 30 minutes or more to obtain a sodium chlorite oxidized solution. This sodium chlorite oxidized solution contains dissolved chlorine dioxide radicals generated by the disproportionation of chlorous acid. These chlorine dioxide radicals are activated by light irradiation.

[0087] Next, stir bars were placed in both tubes of the H-shaped tube, and 1 mL of deuterated chloroform was added to one tube, and 5.7 mL of the sodium chlorite oxidizing solution was added to the other tube. After that, the lids of both tubes of the H-shaped tube were tightly closed. This H-shaped tube was illuminated with an LED lamp (illuminance 90 mW / cm) with a wavelength of 405 nm. 2 The tube was placed 20 cm from the center of the tube and stirred under a 40°C light to allow the reaction to proceed. After the reaction, the deuterated chloroform solution in the H-tube was 13 The generation of phosgene was confirmed by C-NMR measurement. 13 The C-NMR spectrum is shown below. 13 The results of C-NMR spectrum analysis are shown below. As shown below, the generation of phosgene was confirmed by the peak at δ 143.5 ppm. It is believed that chlorine dioxide gas (chlorine dioxide radicals) generated from the sodium chlorite oxidized solution was released into the gas phase in the H-shaped tube and further dissolved in the deuterated chloroform phase, and the chlorine dioxide radicals were further activated by light irradiation and reacted with the deuterated chloroform to generate phosgene.

[0088] After the reaction in Reference Example 1, the deuterated chloroform solution 13 C-NMR spectrum analysis results: 13 C-NMR(100MHz, CDCl3) δ:143.5ppm

[0089] [Example 1] In this example, a nucleophilic reaction product was produced by the method for producing a nucleophilic reaction product of the present invention. More specifically, as shown in Scheme E2 below, chlorine dioxide radicals (halogen oxide radicals) were reacted with chloroform (halogenated hydrocarbon) to generate phosgene (halogenated carbonyl compound) (halogenated carbonyl compound generation step), and the phosgene was then reacted with tetrahydroquinoline (nucleophile) without isolation to produce carbamoyl chloride (nucleophilic reaction product) (nucleophilic reaction product production step).

[0090] [ka]

[0091] In this example, the reaction of Scheme E2 was carried out as follows. First, chloroform (containing 0.3 to 1.0% ethanol) was separated with water and purified through silica gel and alumina to prepare purified chloroform. This purified chloroform served as a reaction solvent, and a portion of it reacted with chlorine dioxide radicals to produce phosgene. Separately, a sodium chlorite oxidizing solution was prepared by mixing 170 mg (1.2 mmol) of sodium chlorite, 5.7 mL of water, and 86 μL of 35% hydrochloric acid and allowing the mixture to stand at room temperature for 30 minutes or more.

[0092] Next, stir bars were placed in both tubes of the H-shaped tube, and 37.6 μL (0.3 mmol, 1 equivalent) of 1,2,3,4-tetrahydroquinoline and 3 mL of the purified chloroform were added to one tube, and 5.7 mL (4 equivalents) of the sodium chlorite oxidizing solution was added to the other tube. The lids of both tubes of the H-shaped tube were then tightly closed. The H-shaped tube was then illuminated with a ring-shaped LED lamp (illumination intensity 3.5 mW / cm) with a wavelength of 405 nm. 2 The mixture was placed in the center of a container and exposed to light for 3 hours while stirring. The LED lamp used was a blue LED light built into an Aldrich microphotochemical reactor (product name ALDRP2). After the solvent was distilled off from the reaction mixture, 1 H-NMR was measured. 1 The yield was calculated from the peak intensity ratio of H-NMR and confirmed that the N-chlorocarbonylated product, carbamoyl chloride, was obtained in 78% yield. 1 The H-NMR spectrum of the starting material, 1,2,3,4-tetrahydroquinoline 1 The H-NMR spectrum is also shown. 1 The results of H-NMR spectrum analysis are shown below. In this example and the following examples, it is believed that phosgene was generated in the chloroform phase (carbonyl halide compound generation step) through a mechanism similar to that of Reference Example 1, and that the phosgene reacted with a nucleophilic agent to generate a nucleophilic reaction product (nucleophilic reaction product production step).

[0093] 1,2,3,4-tetrahydroquinoline 1 H-NMR spectrum analysis results: 1 H-NMR(400MHz, CDCl3) δ:7.00(m,2H), 6.65(t,J=7.6Hz,1H), 6.50(t,J=7.6Hz,1H), 3.32(t,J=5.6Hz,2H), 2.80(t,J=6.4Hz,2H), 1.98(tt,J=5.6,6.4Hz,2H) The post-reaction mixture of Example 1 1 H-NMR spectrum analysis results: 1H-NMR (400MHz, CDCl3) δ:7.63(br,1H), 7.22-7.10(m,3H), 3.93(t,J=6.4Hz,2H), 2.80(t,J=6.4Hz,2H), 2.03(tt,J=6.4,6.4Hz,2H)

[0094] [Example 2] In this example, as shown in Scheme E3 below, chlorine dioxide radicals were reacted with chloroform to generate phosgene in the same manner as in Example 1, and the phosgene was then reacted with tetrahydroquinoline without being isolated to produce carbamoyl chloride. Note that in this example, instead of the ring-shaped LED lamp used in Example 1, an LED lamp with even stronger illuminance (manufactured by Pi Photonics, product name "Hololightkaku") was used as the light source for light irradiation.

[0095] [ka]

[0096] In this example, the reaction of Scheme E3 was carried out as follows. First, chloroform (containing amylene) was used as the solvent. This chloroform was a reaction solvent, and a portion of it reacted with chlorine dioxide radicals to produce phosgene. The sodium chlorite oxidizing solution used was prepared in the same manner as in Example 1.

[0097] Next, stir bars were placed in both tubes of the H-tube, and one tube was charged with 37.6 μL (0.3 mmol, 1 equivalent) of 1,2,3,4-tetrahydroquinoline, 1 mL of chloroform (containing amylene), and 208 μL (1.5 mmol, 5 equivalents) of triethylamine, while the other tube was charged with 5.7 mL (4 equivalents) of the sodium chlorite oxidizing solution. The lids of both tubes of the H-tube were then tightly closed. The H-tube was then illuminated with an LED lamp (illuminance 90 mW / cm) with a wavelength of 405 nm. 2 The mixture was placed 20 cm from the center of the flask and irradiated with light for 45 minutes while stirring. After the reaction, the solvent was removed by distillation, and the mixture was resuspended in deuterated chloroform (CDCl3) as a solvent. 1H-NMR was measured. Meanwhile, the mixture after the reaction was separated with water. Specifically, 5 mL of water and 5 mL of dichloromethane were added to the solution after the reaction to extract the organic layer, and then sodium sulfate was added to dry it, and the solvent was distilled off. The residue was also subjected to the same procedure using deuterated chloroform (CDCl3) as a solvent. 1 H-NMR was measured. 1 The yield was calculated from the peak intensity ratio of H-NMR and confirmed that the N-chlorocarbonylated product, carbamoyl chloride, was obtained in 86% yield. 1 H-NMR spectrum and the residue after separation with water 1 The H-NMR spectrum of the starting material, 1,2,3,4-tetrahydroquinoline 1 The H-NMR spectrum is also shown. 1 The results of the H-NMR spectrum analysis are shown below.

[0098] 1,2,3,4-tetrahydroquinoline 1 H-NMR spectrum analysis results: 1 H-NMR(400MHz, CDCl3) δ:7.00(m,2H), 6.65(t,J=7.6Hz,1H), 6.50(t,J=7.6Hz,1H), 3.32(t,J=5.6Hz,2H), 2.80(t,J=6.4Hz,2H), 1.98(tt,J=5.6,6.4Hz,2H) The post-reaction mixture of Example 2 1 H-NMR spectrum analysis results: 1 H-NMR (400MHz, CDCl3) δ:7.38(br,1H), 7.01-6.98(m,3H), 3.71(t,J=6.4Hz,2H), 2.59(t,J=6.4Hz,2H), 1.82(tt,J=6.4,6.4Hz,2H) The residue after separation with water in Example 2 1 H-NMR spectrum analysis results: 1H-NMR (400MHz, CDCl3) δ:7.65(br,1H), 7.22-7.10(m,3H), 3.92(t,J=6.4Hz,2H), 2.81(t,J=6.4Hz,2H), 2.01(tt,J=6.4,6.4Hz,2H)

[0099] [Example 3] In this example, carbamoyl chloride was produced from tetrahydroquinoline by the same method as in Example 2, Scheme E3, except that the amounts of reactants used and the light irradiation time were slightly changed. Specifically, the reaction was carried out under the same conditions as in Example 2, except that the amount of 1,2,3,4-tetrahydroquinoline used was changed from 0.3 mmol to 0.2 mmol, the amount of chloroform (containing amylene) used was changed from 1 mL to 2 mL, the light irradiation time was changed from 45 minutes to 40 minutes, the amount of sodium chlorite used was changed from 17.0 mg to 113 mg (0.8 mmol), and the amount of 35% hydrochloric acid used was changed from 86 μL to 57 μL. The mixture after the reaction was treated in the same manner as in Example 2, and the reaction mixture was then subjected to the same treatment as in Example 2. 1 The yield was calculated from the peak intensity ratio of H-NMR, and it was confirmed that the N-chlorocarbonylated product, carbamoyl chloride, was obtained in a yield of 95%. That is, the yield of carbamoyl chloride was 86% in Example 2, but was improved to 95% in this Example. In addition, Figure 4 shows the yield of 1,2,3,4-tetrahydroquinoline, the starting material of this Example. 1 H-NMR spectrum of the reaction mixture 1 H-NMR spectrum and the residue after separation with water 1 The H-NMR spectrum is shown along with the reaction scheme of this example.

[0100] [Example 4] In this example, as shown in Scheme E4 below, various amines (Compound 1 below) were reacted with phosgene instead of tetrahydroquinoline to produce the reaction products carbamoyl chloride (Compound 2 below) and urea derivatives (Compound 3 below). In this example, the reaction was carried out under the same reaction conditions as in Example 3 (Condition 1), and further, the reaction was carried out in a system in which the conditions were changed as in Conditions 2 and 3 below. Note that in Conditions 2 and 3 below, the reaction conditions other than those described below were the same as Condition 1 (i.e., the same as in Example 3). Furthermore, in Conditions 2 and 3 below, the "substrate" refers to the reaction raw material, i.e., Compound 1 in Scheme E4 below (individually, Compounds 1b, 1c, 1d, or 1e in Scheme E4 below). Condition 2: Substrate amount 0.1 mmol, chloroform amount 5 mL, triethylamine amount 0.5 mmol Condition 3: Substrate amount 0.4 mmol, chloroform amount 1 mL, triethylamine amount 1.6 mmol, sodium chlorite amount 57 mg, 35% hydrochloric acid amount 28 μL

[0101] [ka]

[0102] In this example, the treatment of the mixture after the reaction was carried out in the same manner as in Example 2 or 3. Furthermore, the same procedures as in Example 2 or 3 were carried out except that tetrachloroethylene C2H2Cl4 was used as the internal standard. 1H-NMR was measured, and the yield was calculated from the peak intensity ratio. As shown in Scheme E4, when 1,2,3,4-tetrahydroisoquinoline (Compound 1b) was used as the starting amine (Compound 1), the yield of the corresponding carbamoyl chloride (Compound 2) was 89% under Condition 2, and the yield of the urea derivative (Compound 3) was 48% under Condition 3. When indoline (Compound 1c) was used as the starting amine (Compound 1), no carbamoyl chloride (Compound 2) was produced under either Condition 1 or Condition 2, and the yield of the urea derivative (Compound 3) was 89% under Condition 2. When piperidine (Compound 1d) was used as the starting amine (Compound 1), the yield of the corresponding carbamoyl chloride (Compound 2) was up to 83% under Condition 2. When pyrrolidine (compound 1e) was used as the raw amine (compound 1), the yield of the corresponding carbamoyl chloride (compound 2) was up to 58% under condition 2, and the yield of the urea derivative (compound 3) was up to 42% under condition 3. Furthermore, regardless of whether compounds 1b, 1c, 1d, or 1e were used as raw materials, the conversion rate to the product (the recovery rate of the product and unreacted raw materials combined) was 100%. Figures 5 to 8 show the various raw materials (starting materials) and reaction mixtures used in this example. 1 The H-NMR chart is shown together with the reaction scheme. Figure 5 shows the results when compound 1b (1,2,3,4-tetrahydroisoquinoline) was reacted under condition 2 or condition 3. Figure 6 shows the results when compound 1c (indoline) was reacted under condition 2. Figure 7 shows the results when compound 1d (piperidine) was reacted under condition 2. Figure 8 shows the results when compound 1e (pyrrolidine) was reacted under condition 2 or condition 3. In addition, each of the following is described below. 1 The analysis results of the H-NMR chart are shown below.

[0103] Reaction of tetrahydroisoquinoline (1b) Raw materials: 1 H-NMR(400MHz, CDCl3) δ:7.13-7.00(m,3H),6.99-6.96(m,1H),3.99(s,1H),3.11(t,J=8.4Hz,2H),2.77(t,J=8.4Hz,2H) Condition 2 After reaction separation: 1H-NMR (400 MHz, CDCl3) of diastereomer mixture δ: 7.10 - 6.96 (m, 4H), 4.70 (s, 0.8H), 4.60 (s, 1.2H), 3.80 - 3.76 (m, 1.2H), 3.71 - 3.66 (m, 0.8H), 2.85 - 2.78 (m, 2H) After the reaction liquid separation treatment of Condition 3: 1 H-NMR (400 MHz, CDCl3) of diastereomer mixture δ: 7.10 - 6.91 (m, 4H), 4.38 (s, 2H), 3.45 (t, J = 8.4 Hz, 2H), 2.85 (t, J = 8.4 Hz, 2H) [

[0104] Reaction of indoline (1c) Raw material: 1 H-NMR (400 MHz, CDCl3) δ: 7.10 (d, J = 7.2 Hz, 1H), 7.02 (dd, J = 7.2, 7.2 Hz, 1H), 6.69 (dd, J = 7.2, 7.2 Hz, 1H), 6.62 (d, J = 7.2 Hz, 1H), 3.72 (br, 1H), 3.51 (t, J = 8.4 Hz, 2H), 3.00 (t, J = 8.4 Hz, 2H) After the reaction liquid separation treatment of Condition 1 (3c): 1 H-NMR (400 MHz, CDCl3) δ: 7.85 (d, J = 8.4 Hz, 2H), 7.22 - 7.17 (m, 4H), 7.08 (dd, J = 7.2, 7.2 Hz, 2H), 4.23 (t, J = 8.4 Hz, 4H), 3.18 (t, J = 8.4 Hz, 4H)

[0105] Reaction of piperidine (1d) Raw material: 1 H-NMR (400 MHz, CDCl3) δ: 2.78 (m, 4H), 1.50 (m, 6H) After the reaction liquid separation treatment of Condition 2 (2d): 1 H-NMR (400 MHz, CDCl3) of diastereomer mixture δ: 3.57 - 3.45 (m, 4H), 1.61 - 1.50 (m, 6H)

[0106] Reaction of pyrrolidine (1e) Raw material: 1H-NMR(400MHz, CDCl3) δ:2.80(m,4H),1.66(m,4H) Condition 2 After reaction separation (2e): 1 H-NMR(400MHz, CDCl3) δ:3.50-3.36(m,4H),1.89-1.82(m,4H) Condition 3 After reaction separation (3e): 1 H-NMR(400MHz, CDCl3) δ:3.30-3.26(m,4H),1.77-1.72(m,4H)

[0107] [Example 5] In this example, as shown in Scheme E5 below, various phenols or alcohols (Compound 4 below) were reacted with phosgene as raw materials instead of various amines to attempt to produce reaction products, phenoxycarbonyl chloride (chloroformate, Compound 5 below) and carbonate (Compound 6 below).

[0108] [ka]

[0109] In this example, the reaction of Scheme E5 was carried out in the same manner as in Example 4, except that various phenols or alcohols (compound 4 in Scheme E5) were used as raw materials instead of various amines, and the amounts of various substances used were appropriately changed. However, in this example, only conditions 1 and 2 were examined. The mixture after the reaction was treated in the same manner as in Example 4 (i.e., in the same manner as in Example 2 or 3). Furthermore, as in Example 4, 1 Deuterated chloroform (CDCl3) was used as the solvent for H-NMR, and tetrachloroethylene (C2H2Cl4) was used as the internal standard. 1H-NMR was measured, and the yield was calculated from the peak intensity ratio. As shown in Scheme E5, when phenol (hydroxybenzene), 4-chlorophenol, or 4-nitrophenol was used as the raw material, no corresponding phenoxycarbonyl chloride (compound 5) was produced. On the other hand, the yield of the corresponding carbonate (compound 6) was 99% or higher when phenol (hydroxybenzene) or 4-chlorophenol was used as the raw material (conditions 1 and 2). When 4-nitrophenol was used as the raw material, the yield of the corresponding carbonate (compound 6) was 99% or higher under condition 2. When 1-propanol was used as the raw material, the corresponding phenoxycarbonyl chloride (compound 5) and carbonate (compound 6) were produced, and the yield of phenoxycarbonyl chloride (compound 5) was 41% under condition 2. When any raw material was used, the conversion rate to the product (the recovery rate of the product and unreacted raw material combined) was 100%. 9 to 12 show the various raw materials (starting materials) and reaction mixtures used in this example. 1 The H-NMR chart is shown together with the reaction scheme. Figure 9 shows the result when phenol (hydroxybenzene) was reacted under condition 2. Figure 10 shows the result when 4-chlorophenol was reacted under condition 1. Figure 11 shows the result when 4-nitrophenol was reacted under condition 2. Figure 12 shows the result when 1-propanol (n-propyl alcohol) was reacted under condition 1. In addition, each 1 The analysis results of the H-NMR chart are shown below.

[0110] Reaction of phenol (4a) Raw materials: 1 H-NMR (400MHz, CDCl3) δ:7.28(dd,J=7.8, 8.0Hz,2H),6.99(t,J=7.8Hz,1H),6.89(d,J=8.0Hz,1H) Condition 2 After reaction separation (6a): 1 H-NMR(400MHz, CDCl3) δ:7.43-7.37(m,2H),7.28-7.24(m,3H)

[0111] 4-クロロフェノール (4b) no reaction raw material: 1 H-NMR (400MHz, CDCl3) δ:7.18(d,J=8.4Hz,2H),6.76(d,J=8.4Hz,2H),5.13(br,1H) Condition 1: After liquid separation treatment (6b): 1 H-NMR(400MHz, CDCl3) δ:7.38(d,J=7.2Hz,4H),7.22(d,J=7.2Hz,4H)

[0112] 4-ニトロフェノール (4c) no reaction raw material: 1 H-NMR (400MHz, CDCl3) δ:8.17(d,J=9.2Hz,2H),6.92(d,J=9.2Hz,2H),5.85(br,1H) Condition 2: After liquid separation treatment (6c): 1 H-NMR(400MHz, CDCl3) δ:8.32(d,J=9.2Hz,4H),7.48(d,J=9.2Hz,4H)

[0113] 1-プロパノール (4d) reaction raw material: 1 H-NMR(400MHz, CDCl3) δ:3.59(t,J=6.4Hz,2H),1.57(tt,J=9.2Hz,2H),5.85(br,1H) Condition 1: After liquid separation treatment (5d): 1 H-NMR (400MHz, CDCl3) δ:3.27(t,J=6.4Hz,2H),1.71(tq,J=6.4,6.4Hz,2H),0.98(t,J=6.4Hz,3H) After reaction liquid separation treatment (6d): 1 H-NMR (400MHz, CDCl3) δ:3.98(t,J=6.4Hz,2H),1.52(tq,J=6.4,6.4Hz,2H),0.96(t,J=6.4Hz,3H)

[0114] [Example 6] In this example, as shown in Scheme E6 below, chlorine dioxide radicals were reacted with chloroform to generate phosgene, as in Examples 1 to 3, and the phosgene was then reacted with tetrahydroquinoline without isolation to produce carbamoyl chloride. Note that in this example, sunlight was used as the light source for light irradiation instead of the ring-shaped LED lamp in Example 1 and the LED lamps in Examples 2 and 3.

[0115] [ka]

[0116] In this example, the reaction of Scheme E6 was carried out as follows. First, chloroform (containing amylene) was used as the solvent. This chloroform was a reaction solvent, and a portion of it reacted with chlorine dioxide radicals to produce phosgene. The sodium chlorite oxidizing solution used was prepared in the same manner as in Example 1.

[0117] Next, stir bars were placed in both tubes of the H-shaped tube, and 25.1 μL (0.2 mmol, 1 equivalent) of 1,2,3,4-tetrahydroquinoline, 2.0 mL of chloroform (containing amylene), and 138 μL (1.0 mmol, 5 equivalents) of triethylamine were added to one tube, and 5.7 mL (4 equivalents) of the sodium chlorite oxidizing solution was added to the other tube. Then, the lids of both tubes of the H-shaped tube were tightly closed. This H-shaped tube was placed in sunlight and irradiated with sunlight for 2 hours while stirring. The experiment date was March 10, 2021, and the sunlight irradiation time was from 11:20 to 13:20, and the weather was sunny. After distilling off the solvent from the mixture after the reaction, deuterated chloroform (CDCl3) was used as the solvent. 1 H-NMR was measured. Meanwhile, the mixture after the reaction was separated with water. Specifically, 5 mL of water and 5 mL of dichloromethane were added to the solution after the reaction to extract the organic layer, and then sodium sulfate was added to dry it, and the solvent was distilled off. The residue was also subjected to the same procedure using deuterated chloroform (CDCl3) as a solvent. 1 H-NMR was measured. 1The yield was calculated from the peak intensity ratio of H-NMR, and it was confirmed that the N-chlorocarbonylated product, carbamoyl chloride, was obtained in a yield of 96%. That is, this example confirmed that the target product (nucleophilic reaction product) can be produced in extremely high yield by the method for producing a nucleophilic reaction product of the present invention, even when sunlight (natural light) is used instead of an artificial light source.

[0118] [Example 7] In this example, ethylene glycol was selected as the substrate (i.e., raw material or starting material) to react with phosgene in a 1:1 molar ratio. In this example, 0.5 equivalents of chlorine dioxide were reacted with ethylene glycol as shown in Scheme E7 below, and the product was obtained in 61% yield. This suggests that chlorine dioxide acted as an initiator and oxygenating agent for the radical chain reaction in this example.

[0119] [ka]

[0120] In this example, the reaction of Scheme E7 was carried out as follows. First, stir bars were placed in both tubes of an H-tube. Next, 22.3 μL (0.4 mmol, 1 equivalent) of ethylene glycol, 4 mL of chloroform (containing amylene), and 161 μL (2.0 mmol, 5 equivalents) of pyridine were added to one tube of the H-tube. Furthermore, 5.7 mL (0.5 equivalents) of the sodium chlorite oxidizing solution was added to the other tube of the H-tube. Then, the lids of both tubes of the H-tube were tightly closed. This H-tube was illuminated with an LED lamp (illuminance 90 mW / cm) with a wavelength of 405 nm. 2 The mixture was placed 20 cm from the center of the flask and exposed to light for 3 hours while stirring to allow the reaction to proceed. After the reaction, the solvent was removed by distillation, and the mixture was resuspended in deuterated chloroform (CDCl3) as a solvent. 1 H-NMR was measured and the yield was calculated from the peak intensity ratio, confirming that the carbonylated target product, cyclic carbonate, was obtained in a yield of 61%. 1Identification by H-NMR confirmed the known identity of the starting material (ethylene glycol) and the target product (cyclic carbonate). 1 This was done by comparing with the H-NMR chart.

[0121] In this example, the mechanism by which phosgene (a halogenated carbonyl compound) is generated by the reaction of chlorine dioxide radicals (halogen oxide radicals) with chloroform (a halogenated hydrocarbon) is presumed to proceed, for example, as a radical chain reaction as shown in Scheme II below. 1 O2 * " represents the singlet state of oxygen molecules. In Scheme II below, the numbers "-3.3" and "-14.8" represent the energy difference (unit: kcal mol) before and after the reaction estimated by DFT calculation (M06-2x / 6-311++G(d,p) level). -1 ) and "-60.5(s)" represents the energy difference (unit: kcal mol) before and after the reaction when singlet oxygen (s) is added. -1 ) and "-23.1(t)" represents the energy difference (unit: kcal mol) before and after the reaction when triplet oxygen (t) is added. -1 ) The fact that the energy difference before and after these reactions is a negative value means that the product system (system after the reaction) is lower in energy (i.e., more stable) than the system before the reaction, suggesting that the reaction proceeds exothermically. In this example, light was irradiated using an LED lamp with a wavelength of 405 nm, but as mentioned above, the present invention is not limited to this.

[0122] [ka] [Industrial Applicability]

[0123] As described above, the present invention provides a method for producing a nucleophilic reaction product and a reactant for producing a nucleophilic reaction product, which allows a carbonyl halide compound to be used in a reaction without isolation and can be carried out under mild reaction conditions. As described above, the method for producing a nucleophilic reaction product of the present invention allows a carbonyl halide compound to be used in a reaction without isolation, thereby offering advantages such as high safety, shortening of work steps, and cost reduction. Furthermore, as described above, the method for producing a nucleophilic reaction product of the present invention is applicable to a wide variety of nucleophiles, similar to general reactions between nucleophiles and carbonyl halide compounds, thereby enabling the production of a variety of nucleophilic reaction products. Therefore, the method for producing a nucleophilic reaction product of the present invention is applicable to a very wide range of fields. Furthermore, as described above, the method for producing a nucleophilic reaction product of the present invention can be carried out under mild reaction conditions. Therefore, for example, a nucleophilic reaction product can be produced by applying the method for producing a nucleophilic reaction product of the present invention to raw materials that have been difficult to use in conventional reactions.

[0124] As described above, the present invention is applicable to a wide range of technical fields and has great industrial utility value.

[0125] This application claims priority based on Japanese Patent Application No. 2021-033809, filed on March 3, 2021, the disclosure of which is incorporated herein in its entirety.

Claims

1. a halogenated carbonyl compound generating step of reacting a halogen oxide radical with a halogenated hydrocarbon to generate a halogenated carbonyl compound; a nucleophilic reaction product production step of reacting the carbonyl halide compound with a nucleophilic agent without isolating it to produce a nucleophilic reaction product of the carbonyl halide compound and the nucleophilic agent.

2. 2. The method for producing a nucleophilic reaction product according to claim 1, wherein in the carbonyl halide generating step, the halogen oxide radical is activated by light irradiation.

3. 3. The method for producing a nucleophilic reaction product according to claim 2, wherein in the carbonyl halide generating step, a halogen radical and singlet oxygen are generated from the halogen oxide radical by activation by the light irradiation, and the singlet oxygen is further reacted with the halogenated hydrocarbon to generate the carbonyl halide compound.

4. 4. The method for producing a nucleophilic reaction product according to claim 2, wherein the light irradiated is visible light.

5. The method for producing a nucleophilic reaction product according to any one of claims 1 to 4, wherein the halogen oxide radical is a chlorine dioxide radical.

6. The method for producing a nucleophilic reaction product according to any one of claims 1 to 5, wherein the carbonyl halide compound is phosgene.

7. The method for producing a nucleophilic reaction product according to any one of claims 1 to 6, wherein the nucleophilic reaction product is a carbonylation product of the nucleophile.

8. 8. The method for producing a nucleophilic reaction product according to any one of claims 1 to 7, wherein the nucleophilic agent is at least one selected from the group consisting of amines, carboxylic acids, ammonia, alcohols, phenols, polyols, polyphenols, polyamines, formamide, urea, urea derivatives, carboxylic acid amides, aromatic compounds, α-amino acids, and thiols.

9. The method for producing a nucleophilic reaction product according to any one of claims 1 to 8, wherein the nucleophilic reaction product is at least one selected from the group consisting of amides, halogenated amides, acid halides, esters, carbonates, polycarbonates, polyurethanes, isocyanates, urea, urea derivatives, polyureas, halogenated formates, carbamates, isocyanides, carbodiimides, cyanides, aromatic aldehydes, α-amino acid N-carboxylic anhydrides (NCAs), and thiocarbonates.

10. containing a halogen oxide radical or a halogen oxide radical generator, A reactant for producing a nucleophilic reaction product, characterized in that the halogen oxide radical is reacted with a halogenated hydrocarbon to generate a halogenated carbonyl compound, and the reactant is used in the method for producing the nucleophilic reaction product according to any one of claims 1 to 9.

11. Contains halogenated hydrocarbons, A reactant for producing a nucleophilic reaction product, which is used in the method for producing the nucleophilic reaction product according to any one of claims 1 to 9, by reacting the halogenated hydrocarbon with a halogen oxide radical to generate a halogenated carbonyl compound.

12. containing a nucleophile, A reactant for producing a nucleophilic reaction product, characterized in that the nucleophilic agent is reacted with the carbonyl halide compound generated in the carbonyl halide compound-generating step, and the reactant is used in the method for producing the nucleophilic reaction product according to any one of claims 1 to 9.

Images