WO2020196553A1 - Method for producing n-substituted trihaloacetamide - Google Patents

Abstract

The purpose of the present invention is to provide a method that enables efficient and safe production of an N-substituted trihaloacetamide which also serves as a synthetic intermediate for isocyanate compounds, carbamate compounds, urea compounds, etc. The method for producing an N-substituted trihaloacetamide according to the present invention is characterized by comprising a step for irradiating, with high energy light in the presence of oxygen, a mixture containing a primary amine compound and a tetrahaloethylene having at least one halogeno group selected from chloro-, bromo-, and iodo-.

Description

Method for Producing N-Substituted Trihaloacetamide

The present invention relates to a method capable of safely and efficiently producing N-substituted trihaloacetamide, which is also a synthetic intermediate for isocyanate compounds, carbamate compounds, urea compounds and the like.

Isocyanate compounds having an isocyanate group (-N = C = O) have extremely high reactivity and are used as raw materials for polyurethane and the like. In addition, a specific isocyanate compound is an important synthetic intermediate for active ingredients of pharmaceuticals and pesticides (Patent Document 1).
The isocyanate compound is generally synthesized by reacting a primary amine compound with phosgene (Patent Document 2, etc.). On the other hand, there is also a method of reacting a halogenated alkyl ester of halogenogic acid with a primary amine compound to obtain carbamate and thermally decomposing the carbamate. The halogenated alkyl ester of halogenogic acid is generally produced by reacting a halogenated alcohol with a carbonyl halide such as phosgene.
However, phosgene is a toxic compound that easily reacts with water to generate hydrogen chloride and has a history of being used as a poisonous gas. Phosgene is mainly produced by a highly exothermic gas phase reaction of anhydrous chlorine gas and high-purity carbon monoxide in the presence of an activated carbon catalyst. Chlorine gas and carbon monoxide used here are also toxic. The basic industrial manufacturing process of phosgene has not changed significantly since the 1920s. The production of phosgene by such a process requires expensive and huge equipment. On the other hand, in small to medium scale production, phosgene may be produced by decomposing triphosgene with a base such as triethylamine. However, triphosgene is an expensive reagent, may be decomposed into phosgene by some physical stimulus or chemical stimulus, and is known to have high toxicity itself (Non-Patent Document 1).
The present inventor has developed a method for obtaining a compound such as phosgene by irradiating a halogenated hydrocarbon with light in the presence of oxygen (Patent Document 3). Patent Document 3 describes a method of introducing the generated compound into another reaction vessel and a method of using the generated halogen or carbonyl halide in a chemical reaction in the same system.
In addition, the present inventor has developed a method for producing a halogenated carboxylic acid ester, which comprises irradiating a mixture containing a halogenated hydrocarbon and an alcohol with light in the presence of oxygen (Patent Document 4).
The isocyanate compound can also be obtained by subjecting N-substituted trihaloacetamide to a detrihalomethane reaction (Patent Document 5). Therefore, it can be said that the N-substituted trihaloacetamide is an important precursor compound such as an isocyanate compound.
For example, N-substituted trichloroacetamide is synthesized by reacting hexachloroacetone with a primary amine compound (Patent Document 5 and Non-Patent Document 2). However, hexachloroacetone has lacrimatory properties, has a track record of being used as a herbicide, and is not an inexpensive compound.

Japanese Unexamined Patent Publication No. 3-47159 International Publication No. 2017/104709 Pamphlet Japanese Unexamined Patent Publication No. 2013-181028 International Publication No. 2015/156245 Pamphlet International Publication No. 2011/049023 Pamphlet

An object of the present invention is to provide a method capable of safely and efficiently producing N-substituted trihaloacetamide, which is also a synthetic intermediate for isocyanate compounds, carbamate compounds, urea compounds and the like.

The present inventors have conducted extensive research to solve the above problems. As a result, it was found that N-substituted trihaloacetamide can be safely and efficiently produced by irradiating a mixture containing tetrahaloethylene and a primary amine compound among halogenated hydrocarbons with high-energy light in the presence of oxygen. The present invention was completed.
Hereinafter, the present invention will be shown.

[1] A method for producing N-substituted trihaloacetamide.
It comprises a step of irradiating a mixture containing tetrahaloethylene having one or more halogeno groups selected from chloro, bromo and iodine with a primary amine compound with high energy light in the presence of oxygen. Method.

[2] The method according to the above [1], which comprises a step of heating the mixture without irradiating the high energy light after the high energy light irradiation step.

[3] The method according to [1] or [2] above, wherein a basic compound is not added to the mixture other than the primary amine compound.

[4] The method according to any one of [1] to [3] above, wherein the high-energy light contains light having a wavelength of 180 nm or more and 280 nm or less.

[5] The method according to any one of the above [1] to [4], wherein the tetrachlorethylene is tetrachlorethylene.

[6] A method for producing an isocyanate compound.
The step of producing N-substituted trihaloacetamide by the method according to any one of the above [1] to [5], and
A method comprising a step of treating the N-substituted trihaloacetamide with a basic compound or heating.

[7] A method for producing a carbamate compound, which is a method for producing a carbamate compound.
The step of producing N-substituted trihaloacetamide by the method according to any one of the above [1] to [5], and
A method comprising a step of reacting the above N-substituted trihaloacetamide with a hydroxyl group-containing compound in the presence of a basic compound.

[8] A method for producing a urea compound, which is a method for producing a urea compound.
The step of producing N-substituted trihaloacetamide by the method according to any one of the above [1] to [5], and
A method comprising a step of reacting the above N-substituted trihaloacetamide with an amino group-containing compound in the presence of a basic compound.

[9] An N-substituted trihaloacetamide, which is represented by the following formula (I).

[During the ceremony,
X ¹ represents a halogeno group selected from the group consisting of fluoro, chloro, bromo and iodine, which may be the same or different from each other.
α represents one or more substituents selected from the group consisting of C _1-6 alkyl groups, halogeno groups, nitro groups, and cyano groups.
n represents an integer of 1 or more and 5 or less,
When n is an integer of 2 or more, the plurality of substituents α may be the same or different from each other. ]

[10] An N-substituted trihaloacetamide, which is represented by the following formula (II).

[During the ceremony,
X ² represents a halogeno group selected from the group consisting of fluoro, chloro, bromo and iodine, which may be the same or different from each other.
C _p F _q H _r indicates a divalent fluorocarbonated hydrocarbon group,
p indicates an integer of 1 or more and 10 or less,
q indicates an integer of 1 or more and (2 × p) or less.
r indicates an integer of 0 or more and (2 × p-1) or less.
q + r = 2 × p. ]

In the method of the present invention, it is not necessary to use extremely toxic compounds such as phosgene and carbon monoxide, or expensive catalysts. In addition, a useful N-substituted trihaloacetamide that also serves as a synthetic intermediate for isocyanate compounds, carbamate compounds, urea compounds, etc. can be obtained in high yield. Therefore, the method of the present invention is extremely useful industrially as a technique capable of safely and efficiently producing a useful N-substituted trihaloacetamide.

FIG. 1 is a schematic view showing an example of the configuration of the reactor used in the method of the present invention.

The method for producing an N-substituted trihaloacetamide according to the present invention is a mixture containing tetrahaloethylene having one or more halogeno groups selected from chloro, bromo and iodo, and a primary amine compound in the presence of oxygen. It is characterized by including a step of irradiating high-energy light. The reaction formula for this step is shown below.

[During the ceremony,
X ¹ to X ⁴ independently represent a halogeno group selected from the group consisting of chloro, bromo, and iodine.
X indicates a halogeno group selected from X ¹ to X ⁴ ,
R ¹ represents an m-valent organic group
m represents an integer of 1 or more and 6 or less. ]

Tetrahaloethylene is a compound also called tetrahaloethane and is represented by the following structural formula (III). Hereinafter, in the present disclosure, the compound represented by the structural formula (Y) is abbreviated as "Compound (Y)".

[In the formula, X ¹ to X ⁴ independently represent halogeno groups selected from the group consisting of chloro, bromo, and iodine. ]

In tetrahaloethylene, X ¹ to X ⁴ may be the same or different from each other, but are preferably the same. Further, as X ¹ to X ⁴ , since tetrahaloethylene itself can be preferably used as a solvent, one or more halogeno groups selected from the group consisting of chloro, bromo, and iodine are preferable, and chloro and / /. Alternatively, bromo is more preferable, and chloro is even more preferable from the viewpoint of cost. Specific examples of tetrachlorethylene include tetrachlorethylene and tetrabromoethylene, and tetrachlorethylene is preferable.

Tetrahaloethylene may be appropriately selected according to the desired chemical reaction and product, and one type may be used alone or two or more types may be used in combination. Preferably, only one type of tetrahaloethylene is used depending on the compound to be produced.

The tetrahaloethylene used in the method of the present invention may be, for example, recovered tetrahaloethylene once used as a solvent. At that time, if a large amount of impurities or water is contained, the reaction may be hindered, so purification is preferable to some extent. For example, it is preferable to remove water and water-soluble impurities by washing with water and then dehydrate with anhydrous sodium sulfate, anhydrous magnesium sulfate, or the like. However, even if water is contained, at least the decomposition reaction of tetrahaloethylene proceeds, so that excessive purification that reduces productivity is not necessary. The water content is more preferably 0.5% by mass or less, further preferably 0.2% by mass or less, and even more preferably 0.1% by mass or less. Further, the recycled tetrahaloethylene may contain a decomposition product of tetrahaloethylene or the like. The lower the water content, the more preferable, but from the viewpoint of purification load, the water content is preferably 0.0001% by mass or more.

The primary amine compound is not particularly limited as long as it is a compound having one or more primary amino groups (-NH ₂ groups). For example, in the above reaction scheme, the primary amine compound _{^{R 1 - (NH 2) R}} 1 of _m indicates the m-valent organic group. Examples of such an organic group include a C _1-15 chain aliphatic hydrocarbon group, a C _3-15 cyclic aliphatic hydrocarbon group, a C _6-15 aromatic hydrocarbon group, and these 2 or more and 5 or less groups. Bound groups can be mentioned. Further, m represents an integer of 1 or more and 6 or less, preferably 5 or less, 4 or less or 3 or less, more preferably 1 or 2, and even more preferably 2.

"C _1-15 chain aliphatic hydrocarbon group" refers to a linear or branched saturated or unsaturated aliphatic hydrocarbon group having 1 or more carbon atoms and 15 or less carbon atoms. For example, as the C _1-15 divalent chain aliphatic hydrocarbon group include a C _1-15 alkanediyl group, C _2-15 alkenediyl group, and C _2-15 alkynediyl group.

Examples of the C _1-15 alkanediyl group include methylene, ethylene, n-propylene, isopropylene, n-butylene, 1-methylpropylene, 2-methylpropylene, 1,1-dimethylethylene and 2,2-dimethylethylene. , N-Pentylene, n-Hexylene, n-Heptylene, n-octylene, n-decylene, n-pentadecanilen and the like. It is preferably a C _1-10 alkanediyl group, more preferably a C _1-6 alkanediyl group or a C _1-4 alkanediyl group, and even more preferably a C _1-2 alkanediyl group.

Examples of the C _2-15 alkenyl group include ethenylene (vinylene), 1-propenylene, 2-propenylene (arylene), butenylene, hexenylene, octenylene, desenylene, and pentadecenylene. It is preferably a C _2-10 alkendiyl group, more preferably a C _2-6 alkendiyl group or a C _2-4 alkendiyl group, and even more preferably an ethenylene (vinylene) or 2-propenylene (arylene).

Examples of the C _2-15 alkyndiyl group include ethynylene, propynylene, butynylene, hexynylene, octinilen, pentadecynylene and the like. It is preferably a C _2-10 alkyndiyl group, more preferably a C _2-6 alkyndiyl group or a C _2-4 alkyndiyl group.

"C _3-15 cyclic aliphatic hydrocarbon group" refers to a cyclic saturated or unsaturated aliphatic hydrocarbon group having 1 or more carbon atoms and 15 or less carbon atoms. For example, examples of the C _3-15 divalent cyclic aliphatic hydrocarbon group include a C _3-15 cycloalkanediyl group, a C _4-15 cycloalkendyl group, and a C _4-15 cycloalkindyl group, and C Preferably, _3-10 cycloalkanediyl group, C _4-10 cycloalkendyl group, and C _4-10 cycloalkindyl group.

"C _6-15 aromatic hydrocarbon group" means an aromatic hydrocarbon group having 6 or more carbon atoms and 15 or less carbon atoms. For example, the C _6-15 divalent aromatic hydrocarbon group is phenylene, indenylene, naphthylene, biphenylene, phenalenylene, phenanthrenylene, anthracenylene and the like, preferably a C _6-12 divalent aromatic hydrocarbon group. Yes, more preferably phenylene.

In the above definition of the group, for example, the alkanediyl group refers to a divalent saturated aliphatic hydrocarbon group, but when _m of the amine compound R ¹ − (NH ₂ ) m is 1, it is a monovalent alkyl group. In addition, when m is 3, it shall be read as a trivalent alkanetriyl group. For example, the alkyl group corresponding to methylene, which is an alkanediyl group, is methyl, and the monovalent aromatic hydrocarbon group, which corresponds to phenylene, which is an alkanediyl group, is phenyl.

The organic group may have a substituent other than the nucleophilic group that reacts with the product N-substituted trihaloacetamide (V). Examples of such a substituent include one or more substituents selected from a C _1-6 alkyl group, a C _1-6 alkoxyl group, a halogeno group, and a nitro group. Examples of the "halogeno group" here include fluoro, chloro, bromo, and iodine.

When m = 2, the following group (VI) can be mentioned as R ₁ of the primary amine compound (IV).

[During the ceremony,
R ² and R ³ are independently-(CR ⁵ R ⁶ ) _m3 -or-(-O- (CR ⁵ R ⁶ ) _m4- ) _m5- (In the equation, R ⁵ and R ⁶ are independent. , H or C _1-6 alkyl group, m3 represents an integer of 0 or more and 10 or less, m4 represents an integer of 1 or more and 10 or less, m5 represents an integer of 1 or more and 10 or less, m3 or When m4 is an integer of 2 or more, a plurality of R ⁵ and R ⁶ may be the same or different from each other).
R ⁴ represents one of the following divalent organic groups,

(During the ceremony
R ⁷ and R ⁸ independently have H, a halogeno group, a C _1-20 aliphatic hydrocarbon group which may have a substituent β, and a C _1-20 alkoxyl group which may have a substituent β. , Representing a C _6-20 aromatic hydrocarbon group which may have a substituent γ, or R ⁷ and R ⁸ combine to form a C _3-20 carbocycle or 5-12 membered heterocycle. May
R ⁹ and R ¹⁰ independently represent an H or C _1-6 alkyl group, and if m6 is an integer greater than or equal to 2, multiple R ⁹ and R ¹⁰ may be the same or different from each other. Often,
R ¹¹ to R ¹⁸ independently have a halogeno group, a C _1-20 aliphatic hydrocarbon group which may have a substituent β, a C _1-20 alkoxyl group which may have a substituent β, or _{Represents a} C _6-12 aromatic hydrocarbon group which may have a substituent γ,
R ¹⁹ represents a C _1-9 alkanediyl group which may have a substituent β,
m6 represents an integer of 1 or more and 20 or less.
m7 represents an integer of 1 or more and 500 or less. )
Substituent α1 and substituent α2 are independently a halogeno group, a C _1-20 aliphatic hydrocarbon group, a C _1-20 alkoxyl group, a C _3-20 cycloalkyl group, and a C _6-20 aromatic hydrocarbon group. , C _7-20 aralkyl group, C _6-20 aromatic hydrocarbon oxy group, and C _3-20 cycloalkoxyl group, representing one or more substituents selected from the group.
m1 and m2 independently represent integers of 0 or more and 4 or less.
Substituent β is one or more substituents selected from C _1-6 alkoxyl group, C _1-7 acyl group, halogeno group, nitro group, cyano group, and carbamoyl group.
The substituent γ is one or more substituents selected from a C _1-6 alkyl group, a C _1-6 alkoxyl group, a C _1-7 acyl group, a halogeno group, a nitro group, a cyano group, and a carbamoyl group. ]

Examples of the halogeno group in the primary amine compound (IV) include one or more halogeno groups selected from fluoro, chloro, bromo, and iodine.

Specific examples of the primary amine compound include cyclohexylamine, n-hexylamine, 1,4-diaminobenzene, 2,4-diaminotoluene, 4,4'-diaminodiphenylmethane, and 1,6-diaminohexane. 4,4'-diaminodicyclohexylmethane or isophoronediamine is preferably used.

The amount of the primary amine compound added may be adjusted as appropriate, but for example, it can be 0.05 mmol / mL or more and 50 mmol / mL or less with respect to the initial amount of tetrahaloethylene. If the ratio is 0.05 mmol / mL or more, the reaction is considered to proceed more efficiently, and if the ratio is 50 mmol / mL or less, the primary amine compound reacts with the produced N-substituted trihaloacetamide. Therefore, it is considered that the possibility of by-production of urea compounds is further reduced.

It is preferable not to add a basic compound other than the primary amine compound to the mixture containing at least tetrahaloethylene and the primary amine compound. The basic compound refers to a hydroxide such as an alkali metal or an alkaline earth metal, or an aqueous solution thereof such as ammonia or pyridine having a pH of more than 7. If a basic compound is used in addition to the primary amine compound, the residue of the basic compound deteriorates the quality of the final product, causes side reactions, colors, and requires a purification process to increase the purity. Manufacturing costs may increase.

For example, when tetrahaloethylene is solid or highly viscous at room temperature or reaction temperature, a solvent that does not inhibit the reaction may be further used. Specific examples of such a solvent include aliphatic hydrocarbon solvents such as n-hexane, petroleum ether, ligroine and benzine; aromatic hydrocarbon solvents such as benzene, toluene, xylene and chlorobenzene; diethyl ether, tetrahydrofuran, dioxane and the like. Ether-based solvent; nitrile-based solvent such as acetonitrile can be mentioned.

From the viewpoint of improving the efficiency of the reaction, the above mixture before the start of the reaction contains tetrahaloethylene and a primary amine compound, or tetrahaloethylene, a primary amine compound and a solvent, as well as unavoidable impurities and unavoidable impurities. It is preferable not to add compounds other than the contaminants.

In the present invention, "in the presence of oxygen" may be either a state in which tetrahaloethylene is in contact with oxygen or a state in which oxygen is present in tetrahaloethylene. Therefore, the reaction in this step may be carried out under an air flow of a gas containing oxygen, but from the viewpoint of increasing the decomposition efficiency of tetrahaloethylene, the gas containing oxygen can be supplied into tetrahaloethylene by bubbling. preferable.

The oxygen source may be any gas containing oxygen, and for example, air or purified oxygen can be used. The purified oxygen may be mixed with an inert gas such as nitrogen or argon for use. It is preferable to use air from the viewpoint of cost and ease. From the viewpoint of increasing the decomposition efficiency of tetrahaloethylene by irradiation with high-energy light, the oxygen content in the gas used as an oxygen source is preferably about 15% by volume or more and 100% by volume or less. Even when oxygen (oxygen content 100% by volume) is used, the oxygen content can be controlled within the above range by adjusting the oxygen flow rate into the reaction system. The method of supplying the gas containing oxygen is not particularly limited, and the gas may be supplied into the reaction system from an oxygen cylinder equipped with a flow rate regulator, or may be supplied into the reaction system from an oxygen generator.

The amount of gas containing oxygen may be appropriately determined according to the amount of tetrahaloethylene, the shape of the reaction vessel, and the like. For example, it is preferable that the amount of gas supplied to the reaction vessel per minute with respect to tetrahaloethylene present in the reaction vessel is 5 volumes or more. The ratio is more preferably 10 volumes or more, and even more preferably 25 volumes or more. The upper limit of the ratio is not particularly limited, but is preferably 500 volume times or less, more preferably 250 volume times or less, and even more preferably 150 volume times or less. Further, the amount of oxygen supplied to the reaction vessel per minute with respect to the tetrahaloethylene present in the reaction vessel can be 1 volume or more and 25 volume or less. If the gas flow rate is too high, tetrahaloethylene may volatilize, while if it is too low, the reaction may be difficult to proceed. The oxygen supply rate can be, for example, 0.01 L / min or more and 10 L / min or less with respect to 20 mL of tetrahaloethylene.

The high-energy light irradiating the mixture is light having sufficient energy to decompose tetrahaloethylene. For example, light containing UV-B having a wavelength of 280 nm or more and 315 nm or less and / or UV-C having a wavelength of 180 nm or more and 280 nm or less can be used, and it is preferable to use light containing UV-C having a wavelength of 180 nm or more and 280 nm or less. In addition, sunlight also contains a few percent of ultraviolet rays, and the light of fluorescent lamps also contains a very small amount of ultraviolet rays, but the light of fluorescent lamps and the sunlight that reaches the ground surface do not contain UV-C, and tetra. These are not included in the high-energy light of the present invention because they do not have enough energy to decompose haloethylene. Preferably, high-energy light whose peak wavelength is within the above range is used.

The means of light irradiation is not particularly limited as long as it can irradiate light of the above wavelength range, but examples of the light source containing a sufficient amount of light in the above wavelength range in the wavelength range include a low pressure mercury lamp and a medium pressure mercury lamp. Examples thereof include high-pressure mercury lamps, ultra-high-pressure mercury lamps, chemical lamps, black light lamps, metal halide lamps, and LED lamps. A low-pressure mercury lamp is preferably used from the viewpoint of reaction efficiency and cost.

Conditions such as the intensity of the irradiation light may be appropriately set depending on the type and amount of the starting material used. For example, the desired light intensity at the shortest distance position of the composition from the light source is 1 mW / cm ² or more. It is preferably 50 mW / cm ² or less. The shortest distance between the light source and tetrahaloethylene is preferably 1 m or less, more preferably 50 cm or less, and even more preferably 10 cm or less or 5 cm or less. The lower limit of the shortest distance is not particularly limited, but 0 cm, that is, the light source may be immersed in tetrahaloethylene.

The reaction conditions in this step are not particularly limited and may be adjusted as appropriate. For example, the mixture may be stirred at 30 ° C. or higher and 100 ° C. or lower, or may be heated under reflux.

Examples of the reaction apparatus that can be used in the method of the present invention include a reaction vessel provided with high-energy light irradiation means. The reaction device may be provided with a stirrer and a temperature control means. FIG. 1 shows an aspect of a reactor that can be used in the method of the present invention. The reactor shown in FIG. 1 has a high-energy light irradiation means 1 in a tubular reaction vessel 6. High energy while adding tetrahaloethylene into the tubular reaction vessel 6 and supplying an oxygen-containing gas into the reaction vessel 6 or bubbling the oxygen-containing gas into tetrahaloethylene (not shown). The reaction is carried out by irradiating high-energy light from the light irradiation means 1. When the high-energy light irradiation means 1 is covered with a jacket 2 or the like, the jacket is preferably a material that transmits high-energy light. Further, high-energy light irradiation may be performed from the outside of the reaction vessel. In this case, the reaction vessel is preferably made of a material that transmits high-energy light. The material that transmits high-energy light is not particularly limited as long as it does not interfere with the effects of the present invention, and preferably examples thereof include quartz glass and a fluororesin such as a tetrafluoroethylene / perfluoroalkyl vinyl ether copolymer (PFA). ..

The irradiation time of high-energy light may be appropriately adjusted within a range in which tetrahaloethylene is sufficiently decomposed, but for example, it is preferably 0.5 hours or more and 10 hours or less, more preferably 1 hour or more and 6 hours or less, and 2 hours. More than 4 hours or less is more preferable.

It is preferable that the method of the present invention further includes a step of irradiating the mixture with high-energy light and then heating the mixture without irradiating with high-energy light. This step makes it possible to sufficiently react the decomposition product of tetrahaloethylene with the primary amine compound after the high-energy light irradiation step.

The reaction temperature in this step can be, for example, 50 ° C. or higher and 120 ° C. or lower. Further, the reaction may be carried out in a heated reflux state. The reaction time of this step is not particularly limited, and may be, for example, until the primary amine compound is consumed, but is preferably 0.5 hours or more and 10 hours or less, more preferably 1 hour or more and 6 hours or less, 2 More preferably, it is at least 4 hours or less.

The produced N-substituted trihaloacetamide may be purified by a conventional method. For example, since N-substituted trihaloacetamide is highly reactive, the above mixture after the reaction is allowed to cool to room temperature, and then a poor solvent such as n-hexane is added to precipitate the mixture, and the precipitated N-substituted trihaloacetamide is filtered. It can be purified by taking, washing and / or drying.

In particular, the N-substituted trihaloacetamide represented by the formula (I) is an important synthetic intermediate for the active ingredients of pharmaceuticals and pesticides. In the N-substituted trihaloacetamide (I), the α as the substituent on the benzene ring is preferably an electron-withdrawing group. If the substituent α is an electron-withdrawing group, the electron donating property from the nitrogen atom in the amide group to the carbonyl group is weakened, the desorption ability of the trihalomethyl group is enhanced, and an isocyanate compound or the like can be easily obtained.

Further, the N-substituted trihaloacetamide represented by the formula (II) is useful as a raw material for isocyanate, and by further reacting with a diol compound or a diamino compound, polyurethane or polyurea having high utility value as a water-repellent polymer. It becomes the raw material of.

The N-substituted trihaloacetamide can be converted into an isocyanate compound by treating it with a basic compound as shown in the reaction formula below.

For example, N-substituted trihaloacetamide (V) can be converted to an isocyanate compound (VII) by adding a base to a solution of N-substituted trihaloacetamide (V).

The solvent of the solution of N-substituted trihaloacetamide (V) is not particularly limited as long as it does not inhibit the reaction and exhibits appropriate solubility in N-substituted trihaloacetamide (V). For example, dichloromethane. , Chloroform, carbon tetrachloride and other halogenated hydrocarbons; amide solvents such as dimethylformamide and dimethylacetamide; sulfoxide solvents such as dimethyl sulfoxide; nitrile solvents such as acetonitrile.

The concentration of the solution of N-substituted trihaloacetamide (V) may be adjusted as appropriate, and can be, for example, 0.001 g / mL or more and 1 g / mL or less.

The base is not particularly limited, but one or more bases selected from heterocyclic aromatic amines and non-nucleophilic strong bases because a base having -NH ₂ may react with the produced isocyanate compound. Is preferable.

Heterocyclic aromatic amine refers to a compound containing at least one heterocycle and having at least one amine functional group other than -NH ₂ . Examples of the heterocyclic aromatic amine include pyridine, α-picoline, β-picoline, γ-picoline, 2,3-lutidine, 2,4-lutidine, 2,6-lutidine, 3,5-lutidine, and 2, Examples thereof include pyridines such as -chloropyridine, 3-chloropyridine, 4-chloropyridine, N, N-dimethyl-4-aminopyridine and derivatives thereof.

"Non-nucleophilic strong base" refers to a base with weak nucleophilicity of lone electron pairs on a nitrogen atom due to steric damage, but with strong basicity. For example, triethylamine, N, N-diisopropylethylamine, tripropylamine, triisopropylamine, tributylamine, trypentylamine, trihexylamine, triheptylamine, trioctylamine, tridecylamine, tridodecylamine, triphenylamine, Tribenzylamine, N, N-diisopropylethylamine, 1,5,7-triazabicyclo [4.4.0] deca-5-ene (TBD), 7-methyl-1,5,7-triazabicyclo [ 4.4.0] Deca-5-ene (MTBD), 1,8-diazabicyclo [5.4.0] Undec-7-ene (DBU), 1,5-diazabicyclo [4.3.0] nona- 5-ene (DBN) and 1,1,3,3-tetramethylguanidine (TMG) can be mentioned. In addition, general-purpose organic amines such as trimethylamine, dimethylethylamine, diethylmethylamine, N-ethyl-N-methylbutylamine, and 1-methylpyrrolidine can also be used.

The amount of the base used may be adjusted as appropriate, and for example, it can be used in an amount of 1 time or more and 50 times or less with respect to 1 mol of N-substituted trihaloacetamide (V).

The reaction conditions of this reaction may be adjusted as appropriate. For example, the reaction can be carried out at room temperature, more specifically at 5 ° C. or higher and 40 ° C. or lower. As for the reaction time, since this reaction proceeds very quickly due to the excellent desorption ability of ₃ -CX groups, for example, a base is added to a solution of N-substituted trihaloacetamide (V) and then the mixture is stirred for 1 second. It can be 1 hour or less.

In addition, some N-substituted trihaloacetamides (V) are converted to isocyanate compounds (VII) only by heating. The temperature in this case depends on the N-substituted trihaloacetamide (V), but can be, for example, 150 ° C. or higher and 350 ° C. or lower.

Since the reactivity of both the N-substituted trihaloacetamide (V) and the isocyanate compound (VII) is very high, carbamate is carried out by reacting the N-substituted trihaloacetamide (V) with the hydroxyl group-containing compound in the presence of a basic compound. Compounds can be produced. For example, the reaction between an N-substituted trihaloacetamide having one trihaloacedoamide group and a hydroxyl group-containing compound is as follows.

[During the ceremony,
X is synonymous with the above
R ²⁰ and R ²¹ independently represent the monovalent organic group of R ¹ . ]

Further, a urea compound can be produced by reacting an N-substituted trihaloacetamide (V) with an amino group-containing compound in the presence of a basic compound. For example, the reaction between an N-substituted trihaloacetamide having one trihaloacedoamide group and an amino group-containing compound is as follows.

[In the formula, X, R ²⁰ and R ²¹ have the same meaning as above. ]

Further, as shown in the reaction formula below, polycarbamate (polyurethane) or polyurea is produced by reacting an N-substituted trihaloacetamide having two trihaloacedamide groups with a compound having two hydroxyl groups or amino groups. You can also do it. Examples of the N-substituted trihaloacetamide having two trihaloacedoamide groups include N-substituted trihaloacetamide represented by the formula (II).

[During the ceremony,
X is synonymous with the above
Z indicates O or NH,
R ²² and R ²³ independently represent the divalent organic group of R ¹ . ]

During the above reaction, when at least one of the N-substituted trihaloacetamide and the hydroxyl group-containing compound or the amino group-containing compound is liquid at room temperature or the reaction temperature, a solvent may not be used, but a solvent may be used. The solvent is not particularly limited as long as it does not inhibit the reaction and exhibits appropriate solubility in the raw material compound. For example, an aliphatic hydrocarbon solvent such as hexane; an aromatic hydrocarbon solvent such as toluene is used. Solvents; halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride; nitrile solvents such as acetonitrile; amide solvents such as dimethylformamide and dimethylacetamide; sulfoxide solvents such as dimethyl sulfoxide; ether solvents such as tetrahydrofuran be able to.

As the base, the same base as one or more bases selected from the heterocyclic aromatic amine and the non-nucleophilic strong base used in the method for producing an isocyanate compound can be used. The amount of the base used may be appropriately adjusted, and for example, it can be used in an amount of 1-fold molar or more and 50-fold molar or less with respect to N-substituted trihaloacetamide (V).

The reaction conditions may be adjusted as appropriate, but for example, the reaction temperature can be 10 ° C. or higher and 120 ° C. or lower, and the reaction time can be 1 hour or longer and 50 hours or lower.

After the reaction, the carbamate compound and the urea compound are relatively stable, so normal post-treatment may be performed. For example, an organic solvent immiscible with water such as chloroform or ethyl acetate and an aqueous solvent such as water, hydrochloric acid, or saturated saline are added to the reaction solution after the reaction to separate the solutions, and the organic layer is separated by anhydrous sodium sulfate or anhydrous magnesium sulfate. After drying with or the like and concentrating, it may be washed with a poor solvent such as n-hexane, or purified by chromatography or recrystallization. Since the polyurethane compound and the polyurea compound may have low solubility, a poor solvent may be directly added to the reaction solution to precipitate them.

This application claims the benefit of priority based on Japanese Patent Application No. 2019-60647 filed on March 27, 2019. The entire contents of the specification of Japanese Patent Application No. 2019-60647 filed on March 27, 2019 are incorporated herein by reference.

Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited by the following examples as well as the present invention, and appropriate modifications are made to the extent that it can be adapted to the gist of the above and the following. Of course, it is possible to carry out, and all of them are included in the technical scope of the present invention.

Example 1: Synthesis of 2,2,2-trichloro-N-phenylacetamide

Tetrachlorethylene (20 mL, 195 mmol) and aniline hydrochloride (5.23 g, 40 mmol) are placed in a cylindrical flask with a diameter of 42 mm, and a quartz glass jacket with a diameter of 30 mm and a low-pressure mercury lamp (“UVL20PH-6” manufactured by SEN LIGHTS, 20 W) are placed. , Φ24 × 120 mm) was attached to assemble the reactor schematically shown in FIG. The reaction solution was bubbled with oxygen at a rate of 0.5 L / min and irradiated with light at 80 ° C. for 3 hours under stirring conditions. The light irradiation was stopped, the bath temperature was raised to 150 ° C., and the mixture was refluxed for 2 hours. The unreacted components of the photolysis gas were treated by passing through a saturated aqueous solution of NaHCO ₃ . When heating and oxygen bubbling were stopped, the mixture was allowed to stand until room temperature, dichloromethane was added as an internal standard, and the NMR yield was measured, it was confirmed that the desired product was obtained in a yield of> 99%. Precipitation was formed when n-hexane was added to the sample solution. When the precipitate was collected by suction filtration and dried, the target substance of a flesh-colored solid could be isolated (yield: 59%, yield: 5.6 g, 23.5 mmol).
^{1 1} H NMR (500 MHz, CDCl ₃ , 20 ° C.): δ8.33 (br, 1H, NH), 7.58 (d, J = 7.5 Hz, 2H, Phenyl), 7.41 (t, J = 7) .5Hz, 2H, Phenyl), 7.24 (t, J = 7.5Hz, 1H, Phenyl)
¹³ C NMR (125 MHz, CDCl ₃ , 20 ° C.): δ159.19, 135.91, 129.33, 126.05, 120.33, 92.81
FT-IR (ATR): 3306, 1693, 1600, 1528, 1498, 1444, 1245, 877, 823, 833, 742,686,639 cm ^-1
FAB-MS: m / z calculated for [M + H] ⁺ (C ₈ H ₆ Cl ₃ NO) 237.9515, found 237.8063

Example 2: 2,2,2-trichloro-N-cyclohexylacetamide

Tetrachlorethylene (20 mL, 195 mmol) and cyclohexylamine (2.3 mL, 20 mmol) were placed in a cylindrical flask with a diameter of 42 mm, and a quartz glass jacket with a diameter of 30 mm and a low-pressure mercury lamp (“UVL20PH-6” manufactured by SEN LIGHTS, 20W, φ24 × 120 mm) was attached to assemble the reactor schematically shown in FIG. The reaction solution was bubbled with oxygen at a rate of 0.5 L / min and irradiated with light at 70 ° C. for 2 hours under stirring conditions. The light irradiation was stopped, and the reaction solution was continuously stirred at 70 ° C. for 2.5 hours. The unreacted components of the photolysis gas were treated by passing through a saturated aqueous solution of NaHCO ₃ . When heating and oxygen bubbling were stopped, the mixture was allowed to stand until it reached room temperature, dichloromethane was added as an internal standard, and the NMR yield was measured, it was confirmed that the desired product was obtained in 88% yield.

Example 3: 2,2,2-trichloro-N-hexylacetamide

Tetrachlorethylene (20 mL, 195 mmol) and n-hexylamine (2.6 mL, 20 mmol) were placed in a cylindrical flask with a diameter of 42 mm, and a quartz glass jacket with a diameter of 30 mm and a low-pressure mercury lamp (“UVL20PH-6” manufactured by SEN LIGHTS, Inc., 20 W, φ24 × 120 mm) was attached to assemble the reactor schematically shown in FIG. The reaction solution was bubbled with oxygen at a rate of 0.5 L / min and irradiated with light at 100 ° C. for 2 hours under stirring conditions. Light irradiation was stopped, and the reaction solution was continuously stirred at 100 ° C. for 1 hour. The unreacted components of the photolysis gas were treated by passing through a saturated aqueous solution of NaHCO ₃ . When heating and oxygen bubbling were stopped, the mixture was allowed to stand until room temperature, dichloromethane was added as an internal standard, and the NMR yield was measured, it was confirmed that the desired product was obtained in a yield of 65%.

Example 4: N-Butyl-2,2,2-trichloroacetamide

Tetrachlorethylene (20 mL, 195 mmol) and n-butylamine (1.0 mL, 10 mmol) are placed in a cylindrical flask with a diameter of 42 mm, and a quartz glass jacket with a diameter of 30 mm and a low-pressure mercury lamp (“UVL20PH-6” manufactured by SEN LIGHTS, 20 W) are placed. , Φ24 × 120 mm) was attached to assemble the reactor schematically shown in FIG. The reaction solution was bubbled with oxygen at a rate of 0.5 L / min and irradiated with light at 70 ° C. for 2 hours under stirring conditions. Light irradiation was stopped, and the reaction solution was continuously stirred at 70 ° C. for 1 hour. The unreacted components of the photolysis gas were treated by passing through a saturated aqueous solution of NaHCO ₃ . Heating and oxygen bubbling were stopped, the mixture was allowed to stand until it reached room temperature, dichloromethane was added as an internal standard, and the NMR yield was measured. As a result, it was confirmed that the desired product was obtained in a yield of 97%.

Example 5: N, N'-(hexane-1,6-diyl) bis (2,2,2-trichloroacetamide)

Tetrachlorethylene (20 mL, 195 mmol) and 1,6-diaminohexane (1.17 g, 10 mmol) are placed in a cylindrical flask with a diameter of 42 mm, and a quartz glass jacket with a diameter of 30 mm and a low-pressure mercury lamp (“UVL20PH-6” SEN LIGHTS) , 20 W, φ24 × 120 mm) was attached to assemble the reactor schematically shown in FIG. The reaction solution was bubbled with oxygen at a rate of 0.5 L / min and irradiated with light at 80 ° C. for 2.5 hours under stirring conditions. The light irradiation was stopped, the bath temperature was raised to 150 ° C., and the mixture was refluxed for 2 hours. The unreacted component of the photodegradable gas was treated by passing it through a saturated aqueous solution of NaHCO ₃ . Heating and oxygen bubbling were stopped, allowed to stand to room temperature, and n-hexane was added to cause precipitation. When the precipitate was collected by suction filtration and dried, the desired substance of the flesh-colored solid could be isolated (yield: 68%, yield: 2.8 g, 6.8 mmol). The obtained N, N'-(hexane-1,6-diyl) bis (2,2,2-trichloroacetamide) was thermally decomposed at about 279 ° C. and converted into the corresponding diisocyanate compound.
^{1 1} H NMR (500 MHz, DMSO-d ₆ , 20 ° C.): δ9.00 (br, 2H, NH), 1.58 (q, J = 6.7 Hz, 4H), 1.49 (quin, J = 6) .7Hz, 4H), 1.28 (quin, J = 6.7Hz, 4H)
¹³ C NMR (125 MHz, DMSO-d ₆ , 20 ° C.): δ161.26.92.90,40.49,28.09,25.62
FT-IR (ATR): 3318, 2953, 2926, 2858, 1696, 1528, 1439, 1293, 1263, 1219, 818, 739, 642 cm ^-1
FAB-MS: m / z calculated for [M + H] ⁺ (C ₁₀ H ₁₄ Cl ₆ N ₂ O ₂ ) 406.9157, found 406.7796

Example 6: N, N'-(4-methyl-1,3-phenylene) bis (2,2,2-trichloroacetamide)

Tetrachlorethylene (20 mL, 195 mmol) and 2,4-diaminotoluene (1.23 g, 10 mmol) are placed in a cylindrical flask with a diameter of 42 mm, and a quartz glass jacket with a diameter of 30 mm and a low-pressure mercury lamp (“UVL20PH-6” SEN LIGHTS) , 20 W, φ24 × 120 mm) was attached to assemble the reactor schematically shown in FIG. The reaction solution was bubbled with oxygen at a rate of 0.5 L / min and irradiated with light at 80 ° C. for 2.5 hours under stirring conditions. The light irradiation was stopped, the bath temperature was raised to 150 ° C., and the mixture was refluxed for 2 hours. The unreacted components of the photolysis gas were treated by passing through a saturated aqueous solution of NaHCO ₃ . Heating and oxygen bubbling were stopped, allowed to stand to room temperature, and n-hexane was added to cause precipitation. When the precipitate was collected by suction filtration and dried, the target substance of a flesh-colored solid could be isolated (yield: 70%, yield: 2.9 g, 7.0 mmol).
^{1 1} H NMR (500 MHz, DMSO-d ₆ , 20 ° C.): δ10.89 (s, 1H, NH), 10.65 (s, 1H, NH), 7.58 (s, 1H, Phenyl), 7. 57 (d, J = 7.5Hz, 1H, Phenyl), 7.34 (d, J = 7.5Hz, 1H, Phenyl), 2.19 (s, 3H, Methyl)
¹³ C NMR (125 MHz, DMSO-d ₆ , 20 ° C.): δ160.45, 159.59, 135.32, 134.69, 131.45, 130.65, 120.20, 119.71, 92.81 , 79.05, 16.69
FT-IR (ATR): 3273, 1697, 1613, 1497, 1274, 1230, 838, 812,793, 753, 653, 597 cm ^-1
FAB-MS: m / z calculated for [M + H] ⁺ (C ₁₁ H ₈ Cl ₆ N ₂ O ₂ ) 412.8688, found 421.5064

Example 7: 4,4'-methylene diphenyl diisocyanate (1) N, N'-[methylene di (4,5-phenylene)] bis (2,2,2-trichloroacetamide)

Tetrachlorethylene (20 mL, 195 mmol) and 4,4'-diaminodiphenylmethane (3.95 g, 20 mmol) are placed in a cylindrical flask with a diameter of 42 mm, and a quartz glass jacket with a diameter of 30 mm and a low-pressure mercury lamp ("UVL20PH-6" SEN LIGHTS). A 20 W, φ24 × 120 mm) manufactured by the company was attached to assemble the reaction apparatus schematically shown in FIG. The reaction solution was bubbled with oxygen at a rate of 0.5 L / min and irradiated with light at 80 ° C. for 2 hours under stirring conditions. The light irradiation was stopped, the bath temperature was raised to 150 ° C., and the mixture was refluxed for 2 hours. The unreacted component of the photodegradable gas was treated by passing it through a saturated aqueous solution of NaHCO ₃ . Heating and oxygen bubbling were stopped, allowed to stand to room temperature, and n-hexane was added to cause precipitation. The precipitate was collected by suction filtration and dried to isolate the desired ocher solid (yield: 85%, yield: 8.3 g, 16.9 mmol).
^{1 1} H NMR (500 MHz, DMSO-d ₆ , 20 ° C.): δ7.57 (d, J = 8.5 Hz, 4H, Phenyl), 7.23 (d, J = 8.5 Hz, 4H, Phenyl), 7 .03 (d, J = 7.5Hz, 1H, NH), 6.81 (d, J = 8.0Hz, 1H, NH), 3.93 (s, 2H, Benzyl)
¹³ C NMR (125 MHz, DMSO-d ₆ , 20 ° C.): δ159.54, 138.21, 135.07, 129.21, 128.90, 121.53, 93.00
FT-IR (ATR): 3378, 3329, 1712, 1699, 1597, 1527, 1509, 1408, 1311, 1242, 883,833,730,674,591 cm ^-1
FAB-MS: m / z calculated for [M + H] ⁺ (C ₁₇ H ₁₂ Cl ₆ N ₂ O ₂ ) 488.9001, found 488.6837

(2) 4,4'-Methylene diphenyl diisocyanate

N, N'-[methylenedi (4,5-phenylene)] bis (2,2,2-trichloroacetamide) (120 mg, 0.25 mmol) was added to a 10 mL eggplant-shaped flask, and the mixture was heated at 270 ° C. for 10 minutes. However, a black solid was obtained. Suggested thermal balance-As a result of analysis by mass spectrometry and ¹ H NMR, it was found that the desired product was obtained with an NMR yield of 59%. In addition, the elimination of chloroform, which is a by-product, could be confirmed.

Example 8: N- (2,2,2-trichloroacetyl) benzamide

Tetrachlorethylene (20 mL, 195 mmol) and benzamide (1.22 g, 10 mmol) are placed in a cylindrical flask with a diameter of 42 mm, and a quartz glass jacket with a diameter of 30 mm and a low-pressure mercury lamp (“UVL20PH-6” manufactured by SEN LIGHTS, 20 W, φ24) are placed. × 120 mm) was attached to assemble the reactor schematically shown in FIG. The reaction solution was bubbled with oxygen at a rate of 0.5 L / min and irradiated with light at 50 ° C. for 1.5 hours under stirring conditions. Light irradiation was stopped, the bath temperature was raised to 80 ° C., and the mixture was stirred for 1 hour. The unreacted components of the photolysis gas were treated by passing through a saturated aqueous solution of NaHCO ₃ . Heating and oxygen bubbling were stopped, allowed to stand to room temperature, and n-hexane was added to cause precipitation. The precipitate was collected by suction filtration and dried to isolate the desired substance as a white solid (yield: 30%, yield: 0.8 g, 3.0 mmol).
^{1 1} H NMR (500 MHz, CDCl ₃ , 20 ° C.): δ9.39 (br, 1H, NH), 7.85 (d, J = 8.2 Hz, 2H, Phenyl), 7.68 (t, J = 8) .2Hz, 1H, Phenyl), 7.56 (t, J = 8.2Hz, 2H, Phenyl)
¹³ C NMR (125 MHz, CDCl ₃ , 20 ° C.): δ164.25, 157.63, 133.98, 132.07, 129.28, 127.86, 92.25
FT-IR (ATR): 3280, 1765, 1699, 1505, 1488, 1252, 1177, 1157, 1068, 824, 723, 710, 661,605 cm ^-1
FAB-MS: m / z calculated for [M + H] ⁺ (C ₉ H ₆ Cl ₃ NO ₂ ) 265.9464, found 265.7391

Example 9: N-pentafluorophenyl-2,2,2-trichloroacetamide

Tetrachlorethylene (20 mL, 195 mmol) and pentafluoroaniline (2.26 mL, 20 mmol) are placed in a cylindrical flask with a diameter of 42 mm, and a quartz glass jacket with a diameter of 30 mm and a low-pressure mercury lamp (“UVL20PH-6” manufactured by SEN LIGHTS), 20 W, φ24 × 120 mm) was attached to assemble the reactor schematically shown in FIG. The reaction solution was bubbled with oxygen at a rate of 0.5 L / min and irradiated with light at 80 ° C. for 2 hours under stirring conditions. The light irradiation was stopped, the bath temperature was raised to 150 ° C., and the mixture was refluxed for 2 hours. The unreacted components of the photolysis gas were treated by passing through a saturated aqueous solution of NaHCO ₃ . Heating and oxygen bubbling were stopped, allowed to stand to room temperature, and n-hexane was added to cause precipitation. The precipitate was collected by suction filtration and dried to isolate the desired ocher solid (yield: 65%, yield: 4.2 g, 12.9 mmol).
^{1 1} H NMR (500 MHz, CDCl ₃ , 20 ° C.): δ7.92 (br, 1H, NH)
¹³ C NMR (125 MHz, CDCl ₃ , 20 ° C.): δ160.26, 144.32, 142.30, 140.16, 138.96, 136.96, 110.22, 91.29
¹⁹ F NMR (376 MHz, CDCl ₃ , 20 ° C.): δ-144.22, 153.37, -160.90
FT-IR (ATR): 3264, 1718, 1523, 1496, 1458, 1235, 1151, 1001, 965, 837, 818, 679, 617 cm ^-1
FAB-MS: m / z calculated for [M + H] ⁺ (C ₈ HCl ₃ F ₅ NO) 327.9044, found 327.8010

Example 10: 2,2,2-trichloro-N- (4-fluorophenyl) acetamide

Tetrachlorethylene (20 mL, 195 mmol) and 4-fluoroaniline (1.92 mL, 20 mmol) are placed in a cylindrical flask with a diameter of 42 mm, and a quartz glass jacket with a diameter of 30 mm and a low-pressure mercury lamp (“UVL20PH-6” manufactured by SEN LIGHTS), 20 W, φ24 × 120 mm) was attached to assemble the reactor schematically shown in FIG. The reaction solution was bubbled with oxygen at a rate of 0.5 L / min and irradiated with light at 80 ° C. for 2 hours under stirring conditions. The light irradiation was stopped, the bath temperature was raised to 150 ° C., and the mixture was refluxed for 1 hour. The unreacted components of the photolysis gas were treated by passing through a saturated aqueous solution of NaHCO ₃ . Heating and oxygen bubbling were stopped, allowed to stand to room temperature, and n-hexane was added to cause precipitation. The precipitate was collected by suction filtration and dried to isolate the desired gray solid (yield: 51%, yield: 2.6 g, 10.2 mmol).
^{1 1} H NMR (500 MHz, CDCl ₃ , 20 ° C.): δ8.36 (br, 1H, NH), 7.53-7.56 (m, 2H, Phenyl), 7.08-7.11 (m, 2H) , Phenyl)
¹³ C NMR (125 MHz, CDCl ₃ , 20 ° C.): δ161.35, 159.41, 131.86, 122.44, 116.12, 92.65
¹⁹ F NMR (376 MHz, CDCl ₃ , 20 ° C.): δ-115.24
FT-IR (ATR): 3303,1692,1524,1507,1410,1223,828,816,799cm ^-1
FAB-MS: m / z calculated for [M + H] ⁺ (C ₈ H ₅ Cl ₃ FNO) 255.9421, found 255.7726

Example 11: 2,2,2-trichloro-N- (2-fluorophenyl) acetamide

Tetrachlorethylene (20 mL, 195 mmol) and 2-fluoroaniline (3.87 mL, 40 mmol) are placed in a cylindrical flask with a diameter of 42 mm, and a quartz glass jacket with a diameter of 30 mm and a low-pressure mercury lamp (“UVL20PH-6” manufactured by SEN LIGHTS), 20 W, φ24 × 120 mm) was attached to assemble the reactor schematically shown in FIG. The reaction solution was bubbled with oxygen at a rate of 0.5 L / min and irradiated with light at 80 ° C. for 2.5 hours under stirring conditions. The light irradiation was stopped, the bath temperature was raised to 120 ° C., and the mixture was refluxed for 2 hours. The unreacted components of the photolysis gas were treated by passing through a saturated aqueous solution of NaHCO ₃ . Heating and oxygen bubbling were stopped, allowed to stand to room temperature, and n-hexane was added to cause precipitation. The precipitate was collected by suction filtration and dried to isolate the desired product as a dark brown solid (yield: 85%, yield: 8.7 g, 34.0 mmol).
^{1 1} H NMR (500 MHz, CDCl ₃ , 20 ° C.): δ8.68 (br, 1H, NH), 8.23-8.26 (m, 1H, Phenyl), 7.17-7.21 (m, 3H) , Phenyl)
¹³ C NMR (125 MHz, CDCl ₃ , 20 ° C.): δ163.81,159.35,154.06,152.11,126.46,124.93,121.60,115.23,92.37
¹⁹ F NMR (376 MHz, CDCl ₃ , 20 ° C.): δ-130.23
FT-IR (ATR): 3411, 1766, 1721, 1621, 1599, 1536, 1486, 1458, 1319, 1260, 1216, 1191, 1103, 882,815,750, 670, 579 cm ^-1
FAB-MS: m / z calculated for [M + H] ⁺ (C ₈ H ₅ Cl ₃ FNO) 255.9421, found 255.6852

Example 12: 2,2,2-trichloro-N- (3-fluorophenyl) acetamide

Tetrachlorethylene (20 mL, 195 mmol) and 3-fluoroaniline (3.84 mL, 40 mmol) are placed in a cylindrical flask with a diameter of 42 mm, and a quartz glass jacket with a diameter of 30 mm and a low-pressure mercury lamp (“UVL20PH-6” manufactured by SEN LIGHTS), 20 W, φ24 × 120 mm) was attached to assemble the reactor schematically shown in FIG. The reaction solution was bubbled with oxygen at a rate of 0.5 L / min and irradiated with light at 80 ° C. for 2.5 hours under stirring conditions. The light irradiation was stopped, the bath temperature was raised to 120 ° C., and the mixture was refluxed for 2 hours. The unreacted components of the photolysis gas were treated by passing through a saturated aqueous solution of NaHCO ₃ . Heating and oxygen bubbling were stopped, allowed to stand to room temperature, and n-hexane was added to cause precipitation. When the precipitate was collected by suction filtration and dried, the target substance of a flesh-colored solid could be isolated (yield: 51%, yield: 5.2 g, 20.3 mmol).
^{1 1} H NMR (500 MHz, CDCl ₃ , 20 ° C): δ8.35 (br, 1H, NH), 7.51-7.53 (m, 1H, Phenyl), 7.34-7.37 (m, 1H) , Phenyl), 7.24-7.26 (m, 1H, Phenyl), 6.94-6.95 (m, 1H, Phenyl)
¹³ C NMR (125 MHz, CDCl ₃ , 20 ° C.): δ163.97, 162.01,159.22,137.36,130.51,115.69,112.91,107.95,92.56
¹⁹ F NMR (376 MHz, CDCl ₃ , 20 ° C.): δ-110.31
FT-IR (ATR): 3312, 1697, 1607, 1531, 1489, 1444, 1433, 1221, 841, 833, 773, 672, 640 cm ^-1
FAB-MS: m / z calculated for [M + H] ⁺ (C ₈ H ₅ Cl ₃ FNO) 255.9421, found 255.9473

Example 13: 2,2,2-trichloro-N- (2,2,2-trifluoroethyl) acetamide

Tetrachlorethylene (20 mL, 195 mmol) and 2,2,2-trifluoroethylamine hydrochloride (2.72 g, 20 mmol) are placed in a cylindrical flask with a diameter of 42 mm, and a quartz glass jacket with a diameter of 30 mm and a low-pressure mercury lamp (“UVL20PH-” 6 ”SEN LIGHTS, 20 W, φ24 × 120 mm) was attached to assemble the reactor schematically shown in FIG. The reaction solution was bubbled with oxygen at a rate of 0.5 L / min and irradiated with light at 80 ° C. for 1 hour under stirring conditions. The light irradiation was stopped, the bath temperature was raised to 150 ° C., and the mixture was refluxed for 2 hours. The unreacted components of the photolysis gas were treated by passing through a saturated aqueous solution of NaHCO ₃ . Heating and oxygen bubbling were stopped, allowed to stand to room temperature, and n-hexane was added to cause precipitation. The precipitate was collected by suction filtration and dried to isolate the desired substance as a pale yellow solid (yield: 71%, yield: 3.5 g, 14.2 mmol).
^{1 1} H NMR (500 MHz, CDCl ₃ , 20 ° C.): δ6.99 (br, 1H, NH), 4.01-4.07 (m, 2H, -CH _2- )
¹³ C NMR (125 MHz, CDCl ₃ , 20 ° C): δ162.44, 123.48,91.66,42.52
¹⁹ F NMR (376 MHz, CDCl ₃ , 20 ° C.): δ-72.22
FT-IR (ATR): 3331, 1703, 1672, 1532, 1244, 1397, 1274, 1236, 1158, 842, 823, 665,601 cm ^-1
FAB-MS: m / z calculated for [M + H] ⁺ (C ₄ H ₃ Cl ₃ F ₃ NO) 243.9232, found 243.8126

Example 14: 2,6-difluoro-N- (2,2,2-trichloroacetyl) benzamide

Tetrachlorethylene (20 mL, 195 mmol) and 2,6-difluorobenzamide (3.14 g, 20 mmol) are placed in a cylindrical flask with a diameter of 42 mm, and a quartz glass jacket with a diameter of 30 mm and a low-pressure mercury lamp (“UVL20PH-6” SEN LIGHTS) , 20 W, φ24 × 120 mm) was attached to assemble the reactor schematically shown in FIG. The reaction solution was bubbled with oxygen at a rate of 0.5 L / min and irradiated with light at 50 ° C. for 1 hour under stirring conditions. The light irradiation was stopped, the bath temperature was raised to 120 ° C., and the mixture was refluxed for 1 hour. The unreacted components of the photolysis gas were treated by passing through a saturated aqueous solution of NaHCO ₃ . Heating and oxygen bubbling were stopped, allowed to stand to room temperature, and n-hexane was added to cause precipitation. The precipitate was collected by suction filtration and dried to isolate the desired white solid (yield: 77%, yield: 4.6 g, 15.3 mmol).
^{1 1} H NMR (500 MHz, CDCl ₃ , 20 ° C.): δ9.26 (br, 1H, NH), 7.49-7.53 (m, 1H, Phenyl), 7.01-7.05 (m, 2H) , Phenyl)
¹³ C NMR (125 MHz, CDCl ₃ , 20 ° C.): δ161.03, 159.73, 159.00, 158.06, 133.76, 112.25, 91.63
¹⁹ F NMR (376 MHz, CDCl ₃ , 20 ° C.): δ-111.58
FT-IR (ATR): 3287, 3207, 1771, 1708, 1624, 1591, 1506, 1468, 1281, 1252, 1233, 1173, 1150, 1087, 1011, 839, 822, 794,655,582 cm ^-1
FAB-MS: m / z calculated for [M + H] ⁺ (C ₉ H ₄ Cl ₃ FNO ₂ ) 301.9276, found 301.7060

Example 15: Synthesis of 2,6-difluorobenzoyl isocyanate

2,6-Difluoro-N- (2,2,2-trichloroacetyl) benzamide (10 mg, 33 μmol) was dissolved in chloroform (0.1 mL). A drop of triethylamine was added to the obtained solution at room temperature and mixed. The reaction solution was analyzed by ¹ H NMR and electric field desorption mass spectrometry. As a result, the conversion reaction to isocyanate proceeded quantitatively, and m / z 183, which is the molecular ion peak of 2,6-difluorobenzoyl isocyanate, was detected. It was also confirmed from the isotope pattern that 2,6-difluorobenzoyl isocyanate did not contain chlorine atoms.

Example 16: Synthesis of benzyl isocyanate

N- (2,2,2-trichloroacetyl) benzamide (10 mg, 38 μmol) was dissolved in chloroform (0.1 mL). A drop of triethylamine was added to the obtained solution at room temperature and mixed. When the reaction solution was analyzed under the same conditions as in Example 15, it was confirmed by ^{1 1} H NMR that benzyl isocyanate was quantitatively produced.

Example 17: Synthesis of benzyl benzyl carbamate

In a 50 mL eggplant-shaped flask, put N-benzyl-2,2,2-trichloroacetamide (500 mg, 2 mmol), benzyl alcohol (0.23 mL, 2.2 mmol), and DBU (1.0 mL, 0.15 mmol). And mixed, and stirred at 80 ° C. for 25 hours. Chloroform and hydrochloric acid were added to the reaction solution to separate them, and the organic layer was dried over anhydrous sodium sulfate. The solvent and the unreacted raw material were distilled off under reduced pressure, the obtained solid was washed with n-hexane, the precipitate was collected by suction filtration, and dried, whereby the desired substance of the skin-colored solid could be isolated. (Yield: 77%, Yield: 0.37 g, 1.55 mmol).

Example 18: Synthesis of ethylene bis (N-benzyl carbamate)

N-benzyl-2,2,2-trichloroacetamide (760 mg, 3 mmol), ethylene glycol (89 L, 1.6 mmol), and DBU (1.12 mL, 7.5 mmol) in 30 mL acetonitrile in a 100 mL eggplant-shaped flask. Was dissolved and stirred at 80 ° C. for 21 hours. The solvent and the unreacted raw material were distilled off under reduced pressure. Chlorogen and hydrochloric acid were added to the obtained oily residue to separate the liquids, and the organic layer was dried with anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, the obtained solid was washed with n-hexane, the precipitate was collected by suction filtration, and dried, whereby the desired substance of the flesh-colored solid could be isolated (yield:). 73%, yield: 0.38 g, 1.16 mmol).

Example 19: Synthesis of Hexyl Phenyl Carbamate

In a 100 mL eggplant-shaped flask, in 30 mL of acetonitrile, 2,2,2-trichloro-N-phenylacetamide (720 mg, 3 mmol), 1-hexanol (450 μL, 3.6 mmol), and DBU (1.12 mL, 7. 5 mmol) was dissolved and stirred at 80 ° C. for 16 hours. Chloroform and hydrochloric acid were added to the reaction solution to separate them, and the organic layer was dried over anhydrous sodium sulfate. By distilling off the solvent under reduced pressure, a brown and oily compound could be obtained. As a result of analysis by NMR, it was found that the target product was obtained with an NMR yield of 70%.

Example 20: Synthesis of 1-hexyl-3-phenylurea

In a 50 mL eggplant-shaped flask, 2,2,2-trichloro-N-phenylacetamide (490 mg, 2 mmol), hexylamine (260 μL, 2 mmol), and DBU (300 μL, 2 mmol) were dissolved in 20 mL of acetonitrile, and 80 ° C. Was stirred for 20 hours. Chloroform and hydrochloric acid were added to the reaction solution to separate them, and the organic layer was dried over anhydrous sodium sulfate. A brown solid was obtained by distilling off the solvent under reduced pressure. As a result of analysis by NMR, it was found that the target product was obtained with an NMR yield of 26%.

Example 21: Synthesis of N, N'-(2,2,3,3,4,5,5-octafluorohexane-1,6-diyl) bis (2,2,2-trichloroacetamide)

Tetrachlorethylene (20 mL, 195 mmol) and 2,2,3,3,4,5,5-octafluorohexane-1,6-diaminium chloride (1.00 g, 3.0 mmol) in a cylindrical flask (φ42 mm) A quartz glass jacket (φ30 mm) and a low-pressure mercury lamp (“UVL20PH-6” manufactured by Sen Special Light Source Co., Ltd., 20 W, φ24 × 120 mm) were attached to assemble the reactor. The reaction solution was bubbled with oxygen at a rate of 0.5 L / min and irradiated with light at 50 ° C. for 2.5 hours under stirring conditions. The light irradiation was stopped, the bath temperature was raised to 115 ° C., and the mixture was refluxed for 2 hours. The unreacted components of the photolysis gas were treated by passing through a saturated aqueous solution of NaHCO ₃ . Heating and oxygen bubbling were stopped, allowed to stand to room temperature, and n-hexane was added to cause precipitation. The precipitate was collected by suction filtration and dried to obtain the desired product as a white solid (yield: 84%, yield: 1.4 g, 2.5 mmol).
^{1 1} H NMR (500 MHz, DMSO-d ₆ , 20 ° C.): δ9.65 (s, 2H, NH), 4.05 (s, 4H, NHCH ₂ )
¹³ C NMR (125 MHz, DMSO-d ₆ , 20 ° C): δ162.53,115.60,110.78,91.94
¹⁹ F NMR (376 MHz, DMSO-d ₆ , 20 ° C.): δ-117.10, -123.30
FT-IR (ATR): 3315, 1706, 1530, 1155, 112, 823, 821, 632 cm ^-1
FAB-MS: m / z calculated for [M + H] ⁺ (C ₁₀ H ₆ Cl ₆ F ₈ N ₂ O ₂ ) 550.84, found 550.88

Example 22: Polyurethane synthesis

N, N'-(2,2,3,3,4,5,5-octafluorohexane-1,6-diyl) bis (2,2,2-trichloroacetoamide) in a 50 mL bite eggplant flask (0.27 g, 0.5 mmol), 2,2-bis [4- (2-hydroxyethoxy) phenyl] propane (0.16 g, 0.5 mmol), diazabicycloundecene (0.19 mL, 1.3 mmol) ), And acetonitrile (5 mL) as a solvent, and the mixture was stirred at 90 ° C. for 60 hours. During the reaction, N, N'-(2,2,3,3,4,5,5-octafluorohexane-1,6-diyl) bis (2,2,2-trichloroacetamide) (0.27 g) , 0.5 mmol) was added twice. Then, chloroform, water, and hydrochloric acid were added to the reaction solution to separate the solutions. The organic layer was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and then vacuum dried at 70 ° C. for 2 hours to obtain a light brown solid. As a result of analysis by NMR, it was found that the target product was obtained with an NMR yield of 81%.
^{1 1} H NMR (400 MHz, CDCl ₃ , 20 ° C.): δ / ppm = 7.16-7.08 (br., 4H, phenyl), 6.94-6.86 (br., 2H, NH), 6 .84-6.74 (br., 4H, phenyl), 4.45 (br., 4H, methylene), 4.22-4.04 (m, 4H, methylene), 3.94 (br., 4H) , Ethylene), 1.63 (s, 6H, methyl)
Average molecular weight by HPLC (polystyrene standard): M _w = 2400, M _n = 1900, M _w / M _n = 1.26

1: Light irradiation means, 2: Jacket, 3: Water bath 4: Stirrer, 5: Heat medium or refrigerant, 6: Cylindrical reaction vessel

Claims (10)

1. A method for producing N-substituted trihaloacetamides.
   It comprises a step of irradiating a mixture containing tetrahaloethylene having one or more halogeno groups selected from chloro, bromo and iodine with a primary amine compound with high energy light in the presence of oxygen. Method.
2. The method according to claim 1, further comprising a step of heating the mixture without irradiating the high-energy light after the high-energy light irradiation step.
3. The method according to claim 1 or 2, wherein a basic compound is not added to the mixture other than the primary amine compound.
4. The method according to any one of claims 1 to 3, wherein the high-energy light includes light having a wavelength of 180 nm or more and 280 nm or less.
5. The method according to any one of claims 1 to 4, wherein the tetrachlorethylene is tetrachlorethylene.
6. A method for producing isocyanate compounds,
   A step of producing an N-substituted trihaloacetamide by the method according to any one of claims 1 to 5, and
   A method comprising a step of treating the N-substituted trihaloacetamide with a basic compound or heating.
7. A method for producing carbamate compounds,
   A step of producing an N-substituted trihaloacetamide by the method according to any one of claims 1 to 5, and
   A method comprising a step of reacting the above N-substituted trihaloacetamide with a hydroxyl group-containing compound in the presence of a basic compound.
8. A method for producing urea compounds
   A step of producing an N-substituted trihaloacetamide by the method according to any one of claims 1 to 5, and
   A method comprising a step of reacting the above N-substituted trihaloacetamide with an amino group-containing compound in the presence of a basic compound.
9. An N-substituted trihaloacetamide, which is represented by the following formula (I).
   

   

   
   [During the ceremony,
   X ¹ represents a halogeno group selected from the group consisting of fluoro, chloro, bromo and iodine, which may be the same or different from each other.
   α represents one or more substituents selected from the group consisting of C _1-6 alkyl groups, halogeno groups, nitro groups, and cyano groups.
   n represents an integer of 1 or more and 5 or less,
   When n is an integer of 2 or more, the plurality of substituents α may be the same or different from each other. ]
10. An N-substituted trihaloacetamide, which is represented by the following formula (II).
    

    

    
    [During the ceremony,
    X ² represents a halogeno group selected from the group consisting of fluoro, chloro, bromo and iodine, which may be the same or different from each other.
    C _p F _q H _r indicates a divalent fluorocarbonated hydrocarbon group,
    p indicates an integer of 1 or more and 10 or less,
    q indicates an integer of 1 or more and (2 × p) or less.
    r indicates an integer of 0 or more and (2 × p-1) or less.
    q + r = 2 × p. ]

Images