Method for producing fluorinated organic compound

Abstract

Provided is a method for producing a fluorinated organic compound by fluorinating an organic compound in the presence of a fluorinated composition containing IF5, iodine, and an amine and containing 0.12 mol or less of the iodine per 1 mol of the IF5, the method being capable of efficiently synthesizing a fluorinated organic compound.

Description

Technical Field

[0001] The present invention relates to a method for producing a fluorinated organic compound, etc. Background Art

[0002] Fluorine compounds are very important compounds not only as various chemical products such as functional materials, pharmaceutical and pesticide compounds, and electronic materials, but also as their intermediates.

[0003] In recent years, various reactions for introducing fluorine atoms into organic compounds using nucleophilic substitution reactions of fluoride ions and fluorinating agents used in such reactions have been developed.

[0004] Iodine pentafluoride (IF5) is widely known as a strong fluorinating agent having a high oxidizing ability, but it is a liquid fluorinating agent that reacts with moisture in the air to generate HF while decomposing.

[0005] Regarding IF5 having such properties, for example, in Patent Document 1, in Example 27, triethylamine and HF are mixed to prepare an IF5-Et3N-HF complex, and the reaction is carried out in the presence of an excess of iodine (2 equivalents relative to the substrate).

[0006] Prior art literature Patent Literature Patent Document 1: International Publication No. 01 / 096263 Summary of the invention

[0007] Problems to be solved by the invention An object of the present invention is to provide a production method capable of efficiently synthesizing a fluorinated organic compound.

[0008] Technical solutions to solve problems The present invention includes the following configurations.

[0009] Item 1. A method for producing a fluorinated organic compound, comprising the step of fluorinating an organic compound in the presence of a fluorination composition, wherein the fluorination composition comprises IF5, iodine, and an amine, and contains 0.12 mol or less of the iodine per 1 mol of the IF5.

[0010] Item 2. The production method according to Item 1, wherein the content of the iodine is 0.11 mol or less relative to 1 mol of IF5.

[0011] Item 3. The production method according to Item 1 or 2, wherein the amine contains at least one amine selected from the group consisting of aliphatic amines, alicyclic amines, aromatic amines, heterocyclic amines, and polymer-supported amines.

[0012] Item 4. The production method according to any one of Items 1 to 3, wherein the amine contains an aliphatic amine.

[0013] Item 5. The production method according to Item 3 or 4, wherein the aliphatic amine contains a tertiary aliphatic amine.

[0014] Item 6. The production method according to Item 5, wherein the aliphatic tertiary amine contains triethylamine.

[0015] Item 7. The production method according to any one of Items 1 to 6, wherein the fluorinated composition further contains an acid.

[0016] Item 8. The production method according to Item 7, wherein the acid contains a Bronsted acid and / or a Lewis acid.

[0017] Item 9. The production method according to Item 7 or 8, wherein the acid contains HF.

[0018] Item 10. A composition comprising IF5, iodine, and an amine, wherein the composition comprises 0.12 mol or less of the iodine per 1 mol of the IF5.

[0019] Item 11. The composition according to Item 10, wherein the content of the iodine is 0.11 mol or less relative to 1 mol of the IF5.

[0020] Item 12. The composition according to Item 10 or 11, wherein the amine contains at least one amine selected from the group consisting of aliphatic amines, alicyclic amines, aromatic amines, heterocyclic amines, and polymer-supported amines.

[0021] Item 13. The composition according to any one of Items 10 to 12, wherein the amine contains an aliphatic amine.

[0022] Item 14. The composition according to Item 12 or 13, wherein the aliphatic amine contains a tertiary aliphatic amine.

[0023] Item 15. The composition according to Item 14, wherein the aliphatic tertiary amine contains triethylamine.

[0024] Item 16. The composition according to any one of Items 10 to 15, further comprising an acid.

[0025] Item 17. The composition according to Item 16, wherein the acid contains a Bronsted acid and / or a Lewis acid.

[0026] Item 18. The composition according to Item 16 or 17, wherein the acid contains HF.

[0027] Item 19. A fluorination reagent for an organic compound, comprising IF5, iodine and an amine, wherein the iodine is contained in an amount of 0.12 mol or less per mol of the IF5.

[0028] Effects of the Invention The present invention can provide a production method capable of efficiently synthesizing a fluorinated organic compound. DETAILED DESCRIPTION

[0029] The following describes the details and aspects of the production method, composition, etc. of the present invention, but it should be understood that various changes can be made to the details and aspects without departing from the spirit and scope of the scope of the invention.

[0030] 1. Terminology Unless otherwise specified, the symbols and abbreviations in this specification can be understood as the commonly used meanings in the technical field to which the present invention belongs according to the context of this specification.

[0031] In the present specification, “comprising” is a concept including “including”, “consist essentially of” and “consist only of”.

[0032] When a numerical range is expressed by "A to B" in the present specification, it means not less than A and not more than B unless otherwise specified.

[0033] In this manual, "C X ~C Y When "Z group" means a group, unless otherwise specified, it means a Z group having X to Y carbon atoms.

[0034] Unless otherwise specified, the steps, treatments, or operations described in this specification can be performed at room temperature.

[0035] In this specification, room temperature refers to a temperature in the range of 10 to 40°C, preferably 15 to 30°C.

[0036] In the present invention, the term “yield” refers to the ratio (mol %) of the total molar amount of the target compound contained in the outflow gas from the reactor outlet to the molar amount of the raw material compound supplied to the reactor.

[0037] 2. Manufacturing method The production method of the present invention is a production method for fluorinated organic compounds, which includes a step of fluorinating an organic compound in the presence of a fluorination composition, wherein the fluorination composition contains IF5, iodine and amine, and contains 0.12 mol or less of the iodine relative to 1 mol of the IF5.

[0038] By adopting such a manufacturing method, the present invention can efficiently synthesize fluorinated organic compounds. In particular, in the fluorination reaction using IF5, there is often a period (induction period) during which the reaction does not proceed in the initial stage of the reaction (e.g., 0 to 30 minutes, especially 0 to 10 minutes after the start of the reaction). From the perspective of stable production, it is preferably controlled during mass production. However, by using the present invention, the reaction can be efficiently performed even in the initial stage of the reaction (e.g., 0 to 30 minutes, especially 0 to 10 minutes after the start of the reaction).

[0039] (2-1) Organic compounds (reaction substrates) The organic compound used as a reaction substrate in the present invention is preferably a compound that is fluorinated by introducing fluorine atoms into the organic compound by a nucleophilic substitution reaction of a fluoride ion, and is preferably a hydrogen-containing organic compound having at least one hydrogen atom.

[0040] As such an organic compound, from the viewpoint of facilitating the fluorination reaction and improving the efficiency in the initial stage of the reaction, for example, there can be mentioned organic compounds having one or more of a hydroxyl group, a (thio)carbonyl group, a (thio)ether group, an imino group, a (thio)ester group, a (thio)amide group, an epoxy group, an amino group, an aromatic group, an alkenyl group, an alkynyl group, and the like.

[0041] In the present invention, the fluorination of an organic compound as a reaction substrate refers not only to the substitution of hydrogen atoms with fluorine atoms, but also to the substitution (replacement) of the following atoms, groups, etc., especially the above-mentioned groups or their adjacent sites with fluorine atoms, as described later: Hydrogen Atom (CH→CF) Hydroxyl (COH→CF) Carbonyl (C=O→CF2) Thiocarbonyl (C=S→CF2) Thioether (CS→CF) Imino (C=NH→CF2) Hydrazine (C-NHNH2→C-F; C=N-NH2→CF (N=NH)→CF2) Epoxy (C2O→CF-COH).

[0042] Examples of such organic compounds include: (2A) Compounds having a hydroxyl group, (2B) Ketone compounds (including diketones, β-ketocarboxylic acids, β-ketoesters, cyclic ketones, ketals, etc.); aldehyde compounds (including acetals); imine compounds such as Schiff bases and hydrazones; or ester compounds, (2C) sulfide compounds, (2D) Epoxides, (2E) Aromatic compounds (e.g. phenylhydrazine derivatives, phenol derivatives, 2-naphthol derivatives, aniline derivatives, etc.), (2F) Thiocarbonyl compounds, (2G) Polyfluorination of the ethyl portion of an ethyl sulfide compound having a -COOR group, (2H) Unsaturated carbon compounds (e.g. olefin compounds, etc.), etc.

[0043] Among them, from the viewpoints of reaction conversion rate, selectivity of the target product, yield, efficiency in the initial stage of the reaction, etc., preferred are "(2B) ketone compounds (including diketones, β-ketocarboxylic acids, β-ketoesters, cyclic ketones, ketals, etc.); aldehyde compounds (including acetals); imine compounds such as Schiff bases and hydrazones; or ester compounds", "(2F) thiocarbonyl compounds", etc., among which ketone compounds (including diketones, β-ketocarboxylic acids, β-ketoesters, cyclic ketones, ketals, etc.); ester compounds; thiocarbonyl compounds, etc. are more preferred, and ketone compounds (including diketones, β-ketocarboxylic acids, β-ketoesters, cyclic ketones, ketals, etc.); thiocarbonyl compounds, etc. are further preferred, and β-ketoesters, thioketones, dithiocarbamates, etc. are particularly preferred.

[0044] The fluorination in the production method of the present invention is exemplified below, and the fluorinated organic compound as the target product obtained by the production method of the present invention and the organic compound as the reaction substrate are also exemplified.

[0045] Among them, from the viewpoints of reaction conversion rate, selectivity of the target product, yield, efficiency in the initial stage of the reaction, etc., the fluorinated organic compound as the target product is preferably a compound having one or more partial structures generated by the above-mentioned fluorination: -CF-, more preferably a compound having one or more partial structures generated by the above-mentioned fluorination: -CHF- or -CF2-, and further preferably a compound having one or more partial structures generated by the above-mentioned fluorination: -CF3.

[0046] [Fluorination reaction 1] (2A) Fluorination of organic compounds having hydroxyl groups In this fluorination, for example, the following reaction proceeds.

[0047] In the formula, R 1It represents an alkyl group which may have one or more substituents, an aralkyl group which may have one or more substituents, an alkenyl group which may have one or more substituents, an acyl group, a cycloalkyl group which may have one or more substituents, or a heterocycloalkyl group which may have one or more substituents.

[0048] R 1a It represents an alkyl group which may have one or more substituents, an aryl group which may have one or more substituents, an aralkyl group which may have one or more substituents, an alkenyl group which may have one or more substituents, an acyl group, a cycloalkyl group which may have one or more substituents, or a heterocycloalkyl group which may have one or more substituents.

[0049] In the fluorination reaction 1, as R 1 and R 1a The alkyl group shown in the figure may be, for example, a linear or branched C1-C12 group such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, neopentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, n-tridecyl, n-tetradecyl, n-pentadecyl, n-hexadecyl, n-heptadecyl, n-octadecyl, or the like. 18 The alkyl group is preferably a linear or branched C1-C6 alkyl group such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, neopentyl, n-hexyl, etc., from the viewpoints of reaction conversion rate, target product selectivity, yield, initial reaction efficiency, etc.

[0050] In the fluorination reaction 1, as R 1 and R 1a Examples of the aralkyl group include C7 to C6 groups such as 2-phenylethyl, benzyl, 1-phenylethyl, 3-phenylpropyl, and 4-phenylbutyl. 10 Aralkyl, etc.

[0051] In the fluorination reaction 1, as R 1 and R 1a Examples of the alkenyl group include C2 to C6 alkenyl groups such as vinyl, allyl, and 3-butenyl.

[0052] In the fluorination reaction 1, as R 1 and R 1a The acyl group shown in the figure includes, for example: Formyl; Straight-chain or branched C2-C6 alkanoyl groups such as acetyl, propionyl, n-butyryl, isobutyryl, n-valeryl, isovaleryl, and pivaloyl; Benzoyl and other C7~C 15 Arylcarbonyl, etc.

[0053] Examples of the acyl group include: Substituted acetyl groups such as chloroacetyl, bromoacetyl, dichloroacetyl, and trifluoroacetyl; Alkoxy substituted acetyl such as methoxyacetyl and ethoxyacetyl; Alkylthioacetyl groups such as methylthioacetyl; Substituted benzoyl groups such as phenoxyacetyl, phenylthioacetyl, 2-chlorobenzoyl, 3-chlorobenzoyl, 4-chlorobenzoyl, 4-methylbenzoyl, 4-tert-butylbenzoyl, 4-methoxybenzoyl, 4-cyanobenzoyl and 4-nitrobenzoyl, and the like.

[0054] In the fluorination reaction 1, as R 1 and R 1a The cycloalkyl group shown includes, for example, C3-C8 cycloalkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. From the viewpoints of reaction conversion rate, selectivity of the target product, yield, efficiency in the initial stage of the reaction, etc., C3-C7 cycloalkyl groups are preferred.

[0055] In the fluorination reaction 1, as R 1 and R 1a Examples of the heterocycloalkyl group include groups in which one or more carbon atoms forming the cyclic structure of the above-mentioned cycloalkyl group are substituted with a nitrogen atom, an oxygen atom, a sulfur atom or the like.

[0056] In fluorination reaction 1, as R 1a Examples of the aryl group include phenyl and naphthyl.

[0057] In the present specification, "may have a substituent" refers to the case where there is a substituent (i.e., substitution) and the case where there is no substituent (i.e., unsubstituted). For example, an alkyl group that may have a substituent includes an alkyl group (i.e., an unsubstituted alkyl group) and an alkyl group that has a substituent (i.e., a substituted alkyl group).

[0058] In the case of having a substituent, the number of substituents of an alkyl group having one or more substituents and an alkenyl group having one or more substituents may be 1 to 5, preferably 1 to 3. Examples of the substituent include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom, etc.), a C1-C6 alkoxy group (methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy, hexyloxy, etc.), a C1-C6 alkylthio group (-S-(C1-C6 alkyl) etc.; the C1-C6 alkyl group may be the above-mentioned group), a cyano group, a nitro group, an amino group, a hydroxyl group, etc., and examples of the alkyl group having a halogen include an alkyl group in which a part or all of the hydrogen atoms of the alkyl group are substituted with fluorine.

[0059] In the case of having a substituent, the number of substituents of an aralkyl group having one or more substituents, an aryl group having one or more substituents, a cycloalkyl group having one or more substituents, a heterocycloalkyl group having one or more substituents, etc., can be, for example, 1 to 5, preferably 1 to 3. Examples of the substituent include the above-mentioned C1-C6 alkyl group, a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom, etc.), a C1-C6 alkoxy group (methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, isobutoxy group, sec-butoxy group, tert-butoxy group, pentyloxy group, hexyloxy group, etc.), a C1-C6 alkylthio group (-S-(C1-C6 alkyl group), etc.; the C1-C6 alkyl group can adopt the above-mentioned groups), a cyano group, a nitro group, an amino group, a hydroxyl group, etc.

[0060] Specific examples of organic compounds having a hydroxyl group that satisfy the above conditions include: Aliphatic alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol, pentanol, hexanol, octanol, decanol, palmityl alcohol, stearyl alcohol, oleyl alcohol, etc. Benzyl alcohol, monosaccharides, disaccharides or trisaccharides having at least one unprotected hydroxyl group, cyclohexanol, alicyclic alcohols such as ascorbic acid; Steroid compounds such as steroid alcohols (e.g. cholesterol, bile acid, cortisone, etc.); Aliphatic monocarboxylic acids such as acetic acid, trifluoroacetic acid, propionic acid, acrylic acid, methacrylic acid, crotonic acid, butyric acid, n-valeric acid, isovaleric acid, neopentanoic acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid and cinnamic acid; Polycarboxylic acids such as oxalic acid, succinic acid, malonic acid, glutaric acid, adipic acid, maleic acid, fumaric acid, and citric acid; Aromatic carboxylic acids such as benzoic acid, salicylic acid, (o-, iso-, para-) terephthalic acid, nalidixic acid, and nicotinic acid; Vitamin compounds with carboxylic acid groups, such as pantothenic acid and biotin; 20 natural amino acids including glycine, alanine, phenylalanine, cysteine, aspartic acid, glutamic acid, threonine, histidine, lysine, methionine, and proline; Carboxylic acid compounds such as hydroxycarboxylic acids (e.g. lactic acid, citric acid, malic acid, tartaric acid, etc.).

[0061] [Fluorination reaction 2] (2B) Ketone compounds (including diketones, β-ketocarboxylic acids, β-ketoesters, cyclic ketones, ketals, etc.); aldehydes Compounds (including acetals); imine compounds such as Schiff bases and hydrazones; or fluorinated ester compounds In this fluorination, for example, the following reaction proceeds.

[0062] Among these formulas, X's are the same or different and represent O or NR' (R' represents a hydrogen atom, an alkyl group which may have one or more substituents, an aralkyl group which may have one or more substituents, an aryl group which may have one or more substituents, an alkenyl group which may have one or more substituents, a cycloalkyl group which may have one or more substituents, a heterocycloalkyl group which may have one or more substituents, a heterocyclic group which may have one or more substituents, an alkoxy group which may have one or more substituents, an aryloxy group which may have one or more substituents, an amino group, a monoalkylamino group which may have one or more substituents, a dialkylamino group which may have one or more substituents, an acyl group or an acylamino group.).

[0063] R 2 , R 2a and R 2c are the same or different and represent a hydrogen atom, an alkyl group which may have one or more substituents, an aralkyl group which may have one or more substituents, an aryl group which may have one or more substituents, an alkenyl group which may have one or more substituents, a cycloalkyl group which may have one or more substituents, a heterocycloalkyl group which may have one or more substituents, a heterocyclic group which may have one or more substituents, an alkoxy group which may have one or more substituents, an aryloxy group which may have one or more substituents, a monoalkylamino group which may have one or more substituents, a dialkylamino group which may have one or more substituents, an acyl group or an acylamino group, or R 2 and R 2a They may also be bonded to each other to form a ring structure.

[0064] R 2b It represents an alkyl group which may have one or more substituents, an aralkyl group which may have one or more substituents, or an aryl group which may have one or more substituents.

[0065] In the fluorination reaction 2, as R', R 2 , R 2a , R 2b and R 2c The alkyl group, aralkyl group and aryl group shown in the figure may be the same as those described above. The preferred specific examples, the types and numbers of substituents are also the same.

[0066] In the fluorination reaction 2, as R', R 2 , R 2a and R 2c The alkenyl group, cycloalkyl group, heterocycloalkyl group and acyl group shown in the formula may be the same as those described above. The preferred specific examples, types and numbers of substituents are also the same.

[0067] In the fluorination reaction 2, as R', R 2 , R 2a and R 2cExamples of the heterocyclic group include piperidinyl, furanyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrrolyl, pyrrolidinyl, triazolyl, benzothiazolyl, benzimidazolyl, oxadiazolyl, thiadiazolyl, indolyl, pyrazolyl, pyridazinyl, cinnolinyl, quinolyl, isoquinolyl, quinoxalinyl, pyrazinyl, pyridyl, benzofuranyl, benzothienyl, tetrazolyl, and other 5-10-membered monocyclic or bicyclic heterocyclic groups having at least one hetero atom selected from nitrogen, oxygen, and sulfur as a ring-constituting atom.

[0068] In the present specification, examples of the aromatic heterocyclic group in the heterocyclic group include a 5- to 10-membered monocyclic or bicyclic heteroaryl group having at least one hetero atom selected from nitrogen, oxygen and sulfur as a ring-constituting atom, such as a furyl group, a thienyl group, an imidazolyl group, an oxazolyl group, a thiazolyl group, a pyrrolyl group, a triazolyl group, a benzothiazolyl group, a benzimidazolyl group, an oxadiazolyl group, a thiadiazolyl group, an indolyl group, a pyrazolyl group, a pyridazinyl group, a cinnolinyl group, a quinolyl group, an isoquinolyl group, a quinoxalinyl group, a pyrazinyl group, a pyridyl group, a benzofuranyl group, a benzothienyl group and a tetrazolyl group.

[0069] In the fluorination reaction 2, as R', R 2 , R 2a and R 2c Examples of the alkoxy group include linear or branched C1-C6 alkoxy groups such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy, and hexyloxy.

[0070] In the fluorination reaction 2, as R', R 2 , R 2a and R 2c Examples of the aryloxy group include phenoxy and naphthyloxy.

[0071] In the fluorination reaction 2, as R', R 2 , R 2a and R 2c Examples of the monoalkylamino group include an amino group monosubstituted with the above-mentioned C1-C6 alkyl group.

[0072] In the fluorination reaction 2, as R', R 2 , R 2a and R 2c Examples of the dialkylamino group include amino groups disubstituted with the above-mentioned C1-C6 alkyl groups, such as dimethylamino, diethylamino, di-n-propylamino, diisopropylamino, dibutylamino, dipentylamino and dihexylamino.

[0073] In the fluorination reaction 2, as R', R 2 , R 2a and R 2cExamples of the acylamino group include acylamino groups having 1 to 8 carbon atoms (for example, formylamino, alkanoylamino, arylcarbonylamino, etc.), such as formylamino, benzylamino, acetylamino, propionylamino, and n-butyrylamino.

[0074] In the case of having a substituent, the number of substituents of the alkoxy group having one or more substituents may be 1 to 5, preferably 1 to 3. Examples of the substituent include a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom, etc.), a C1-C6 alkoxy group (methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy, hexyloxy, etc.), a C1-C6 alkylthio group (-S-(C1-C6 alkyl) etc.; the C1-C6 alkyl group may be the above-mentioned group), a cyano group, a nitro group, an amino group, a hydroxyl group, etc., and examples of the alkyl group having a halogen include an alkyl group in which a part or all of the hydrogen atoms of the alkyl group are substituted with fluorine.

[0075] When having a substituent, the number of substituents such as a heterocyclic group having one or more substituents, an aryloxy group having one or more substituents, a monoalkylamino group having one or more substituents, a dialkylamino group having one or more substituents, an acylamino group having one or more substituents, etc. can be, for example, 1 to 5, preferably 1 to 3. Examples of the substituent include the above-mentioned C1-C6 alkyl groups, halogen atoms (fluorine atoms, chlorine atoms, bromine atoms, iodine atoms, etc.), C1-C6 alkoxy groups (methoxy groups, ethoxy groups, n-propoxy groups, isopropoxy groups, n-butoxy groups, isobutoxy groups, sec-butoxy groups, tert-butoxy groups, pentyloxy groups, hexyloxy groups, etc.), C1-C6 alkylthio groups (-S-(C1-C6 alkyl groups), etc.; the C1-C6 alkyl groups can be the above-mentioned groups), cyano groups, nitro groups, amino groups, hydroxyl groups, etc.

[0076] As R 2 and R 2a Examples of the cyclic structure that can be formed by bonding to each other include aliphatic 4- to 12-membered rings that may have one or more substituents, and aliphatic 4- to 7-membered rings are preferred.

[0077] As R 2 and R 2a Examples of the aliphatic 4- to 7-membered rings that may be bonded to each other to form a cyclic structure include C4-C7 cycloalkane rings such as a cyclobutane ring, a cyclopentane ring, a cyclohexane ring, and a cycloheptane ring.

[0078] In the case of having substituents, the number of substituents of the aliphatic 4- to 7-membered ring having one or more substituents may be 1 to 5, preferably 1 to 3. As substituents, the above-mentioned C1-C6 alkyl groups, halogen atoms (fluorine atoms, chlorine atoms, bromine atoms, iodine atoms, etc.), C1-C6 alkoxy groups (methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy, hexyloxy, etc.), C1-C6 alkylthio groups (-S-(C1-C6 alkyl) etc.; C1-C6 alkyl groups may adopt the above-mentioned groups), cyano, nitro, amino, hydroxyl, carboxyl ester groups (alkoxy-CO- groups; alkoxy groups may adopt the above-mentioned groups), etc. are listed. In addition, the aliphatic 4- to 7-membered ring having one or more substituents also includes

[0079] .

[0080] Examples of the ketone compound satisfying the above conditions include acetone, methyl ethyl ketone, acetylacetone, acetoacetic acid, acetoacetic esters (methyl acetoacetate, ethyl acetoacetate, etc.), cyclohexanone, acetophenone, benzophenone, propiophenone, 4-piperidone, 1-oxo-1,2-dihydronaphthalene, benzylideneacetophenone (chalcone), deoxybenzoin, and ketals thereof.

[0081] Examples of the aldehyde compound satisfying the above conditions include acetaldehyde, propionaldehyde, butyraldehyde, isobutyraldehyde, valeraldehyde, isovaleraldehyde, acrolein, benzaldehyde, cinnamaldehyde, anisaldehyde, nicotinealdehyde, and the like, as well as acetals thereof.

[0082] Examples of imine compounds such as Schiff bases and hydrazones include condensates of the above ketone compounds or aldehyde compounds and appropriate primary amines (methylamine, ethylamine, propylamine, butylamine, pentylamine, hexylamine, cyclohexylamine, ethylenediamine, etc.) or hydrazine.

[0083] Examples of the ester compound satisfying the above conditions include methyl isobutyrate and ethyl isobutyrate.

[0084] [Fluorination reaction 3] (2C) Fluorination of sulfide compounds (including dithioacetals, dithioketals, etc.) In the fluorination, for example, a reaction of substituting one or two hydrogen atoms of a methylene group adjacent to a S atom with a fluorine atom, or substituting a S atom with a fluorine atom is performed.

[0085] In the formula, R 3a , R 3a’ and R 3a”are the same or different and represent an alkyl group which may have one or more substituents, an aralkyl group which may have one or more substituents, an aryl group which may have one or more substituents, an alkenyl group which may have one or more substituents, a cycloalkyl group which may have one or more substituents, a heterocycloalkyl group which may have one or more substituents, or a heterocyclic group which may have one or more substituents, or R 3a and R 3a’ Together they represent an aliphatic 4- to 7-membered ring which may have one or more substituents.

[0086] R 3 and R 3b The same or different groups represent an alkyl group which may have one or more substituents, an aralkyl group which may have one or more substituents, an aryl group which may have one or more substituents, an alkenyl group which may have one or more substituents, a cycloalkyl group which may have one or more substituents, a heterocycloalkyl group which may have one or more substituents, a heterocyclic group which may have one or more substituents, an alkoxy group which may have one or more substituents, an aryloxy group which may have one or more substituents, an amino group, a monoalkylamino group which may have one or more substituents, a dialkylamino group which may have one or more substituents, an acyl group, an acylamino group, a cyano group, an alkylsulfinyl group which may have one or more substituents, and a an aralkylsulfinyl group having one or more substituents, an arylsulfinyl group which may have one or more substituents, a cycloalkylsulfinyl group which may have one or more substituents, a heterocycloalkylsulfinyl group which may have one or more substituents, a sulfinyl group which may have one or more substituents and is bonded to a heterocyclic group, an alkylsulfonyl group which may have one or more substituents, an aralkylsulfonyl group which may have one or more substituents, an arylsulfonyl group which may have one or more substituents, a cycloalkylsulfonyl group which may have one or more substituents, a heterocycloalkylsulfonyl group which may have one or more substituents, or a sulfonyl group which may have one or more substituents and is bonded to a heterocyclic group, or R 3 and R 3b They may also be bonded to each other together with the carbon atoms to which they are bonded, through a hetero atom, or without a hetero atom, to form a 4- to 8-membered ring (the ring may be substituted with at least one substituent selected from the group consisting of a halogen atom, an oxo group, an alkyl group which may have one or more substituents, an aralkyl group which may have one or more substituents, an aryl group which may have one or more substituents, an alkenyl group which may have one or more substituents, a cyano group, and an amino group.).

[0087] R 3c and R 3dare the same or different and represent a hydrogen atom, an alkyl group which may have one or more substituents, an aralkyl group which may have one or more substituents, an aryl group which may have one or more substituents, an alkenyl group which may have one or more substituents, a cycloalkyl group which may have one or more substituents, a heterocycloalkyl group which may have one or more substituents, a heterocyclic group which may have one or more substituents, an alkoxy group which may have one or more substituents, an aryloxy group which may have one or more substituents, a monoalkylamino group which may have one or more substituents, a dialkylamino group which may have one or more substituents, an acyl group or an acylamino group, or R 3c and R 3d They may also be bonded together with the adjacent carbon atoms to form a saturated or unsaturated aliphatic 4- to 7-membered ring having one or more substituents (the ring may be substituted with at least one substituent selected from a halogen atom, an oxy group, an alkyl group which may have one or more substituents, an aralkyl group which may have one or more substituents, an aryl group which may have one or more substituents, an alkenyl group which may have one or more substituents, a cyano group, and an amino group.

[0088] R 3e represents an alkylene group or an arylene group. ).

[0089] In fluorination reaction 3, as R 3 , R 3a , R 3b , R 3c , R 3d , R 3a’ and R 3a” The alkyl, aralkyl, aryl, alkenyl, cycloalkyl, heterocycloalkyl and heterocyclic groups shown in the above-mentioned examples can be used. The preferred specific examples, the types and numbers of substituents are also the same.

[0090] In fluorination reaction 3, as R 3c and R 3d The alkoxy group, aryloxy group, monoalkylamino group, dialkylamino group, acyl group and acylamino group shown in the formula may be the same as those described above, and the preferred specific examples, types and numbers of substituents are also the same.

[0091] In fluorination reaction 3, as R 3a and R 3a’ , R 3c and R 3d The aliphatic 4- to 7-membered ring that can be formed together may be the above-mentioned ring. The preferred specific examples, types and numbers of substituents are also the same.

[0092] In the fluorination reaction 3, as R', R 2 , R 2a and R 2cThe alkylsulfinyl group which may have one or more substituents, the aralkylsulfinyl group which may have one or more substituents, the arylsulfinyl group which may have one or more substituents, the cycloalkylsulfinyl group which may have one or more substituents, the heterocycloalkylsulfinyl group which may have one or more substituents, and the alkyl, aralkyl, aryl, cycloalkyl, heterocycloalkyl and heterocyclic groups of the sulfinyl group which may have one or more substituents bonded to a heterocyclic group may be the same as those described above. The preferred specific examples, the types and the number of substituents are also the same.

[0093] In the fluorination reaction 3, as R', R 2 , R 2a and R 2c The alkylsulfonyl group which may have one or more substituents, the aralkylsulfonyl group which may have one or more substituents, the arylsulfonyl group which may have one or more substituents, the cycloalkylsulfonyl group which may have one or more substituents, the heterocycloalkylsulfonyl group which may have one or more substituents, and the alkyl, aralkyl, aryl, cycloalkyl, heterocycloalkyl and heterocyclic groups of the sulfonyl group which may have one or more substituents bonded to a heterocyclic group may be the same as those described above. The preferred specific examples, the types and the number of substituents are also the same.

[0094] In the fluorination reaction 3, when there is a substituent, R', R 2 , R 2a and R 2c The number of substituents possessed by the alkylsulfinyl group, aralkylsulfinyl group, arylsulfinyl group, cycloalkylsulfinyl group, heterocycloalkylsulfinyl group, sulfinyl group bonded to a heterocyclic group, alkylsulfonyl group, aralkylsulfonyl group, arylsulfonyl group, cycloalkylsulfonyl group, heterocycloalkylsulfonyl group and sulfonyl group bonded to a heterocyclic group may be 1 to 5, preferably 1 to 3. As the substituent, there can be mentioned the above-mentioned C1~C6 alkyl group, halogen atoms (fluorine atom, chlorine atom, bromine atom, iodine atom, etc.), C1~C6 alkoxy groups (methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy, hexyloxy, etc.), C1~C6 alkylthio groups (-S-(C1~C6 alkyl) etc.; the C1~C6 alkyl group can be the above-mentioned groups), cyano group, nitro group, amino group, hydroxyl group, carboxyl ester group (alkoxy-CO- group; the alkoxy group can be the above-mentioned groups), etc.

[0095] In fluorination reaction 3, as R 3 and R 3bExamples of 4- to 8-membered rings that can be formed by bonding together with the carbon atoms to which they are bonded through heteroatoms or without bonding to each other include cyclobutane ring, cyclopentane ring, cyclohexane ring, cycloheptane ring, cyclooctane ring, piperidine ring, furan ring, thiophene ring, imidazole ring, oxazole ring, thiazole ring, pyrrole ring, pyrrolidine ring, and triazine ring.

[0096] In the fluorination reaction 3, when there is a substituent, R 3 and R 3b The number of substituents that can be formed by the 4- to 8-membered rings that can be bonded to the carbon atoms to which they are bonded, through heteroatoms or without heteroatoms, can be 1 to 5, preferably 1 to 3. Examples of the substituents include halogen atoms (fluorine atoms, chlorine atoms, bromine atoms, iodine atoms, etc.), oxy groups, the above-mentioned alkyl groups, the above-mentioned alkenyl groups, cyano groups, and amino groups.

[0097] In fluorination reaction 3, as R 3e Examples of the alkylene group include straight-chain or branched C1-C12 groups such as methylene, ethylene, trimethylene, propylene, and tetramethylene. 18 The alkylene group preferably includes a linear or branched C1-C6 alkylene group.

[0098] In fluorination reaction 3, as R 3e Examples of the arylene group include phenylene (such as 1,4-phenylene) and naphthylene (such as 2,6-naphthylene).

[0099] Examples of the sulfide compound satisfying the above conditions include methyl ethyl sulfide, methyl benzyl sulfide, 2-phenylthioacetate, 2-phenylthioacetophenone, 2-(methylthio)acetophenone, bis(methylthio)methylbenzene, 2-octyl-1,3-dithiane, 2-phenyl-2-trifluoromethyl-1,3-dithiolane, tri(ethylthio)hexane, and 4-tri(methylthio)toluene.

[0100] [Fluorination reaction 4] (2D) Fluorination of epoxy compounds In the fluorination, the addition reaction of fluorine proceeds, for example, by the following reaction.

[0101] In the formula, R 4 , R 4a , R 4b and R 4care the same or different and represent a hydrogen atom, an alkyl group which may have one or more substituents, an aralkyl group which may have one or more substituents, an aryl group which may have one or more substituents, an alkenyl group which may have one or more substituents, a cycloalkyl group which may have one or more substituents, a heterocycloalkyl group which may have one or more substituents, or a heterocyclic group which may have one or more substituents.

[0102] In fluorination reaction 4, as R 4 , R 4a , R 4b and R 4c The alkyl, aralkyl, aryl, alkenyl, cycloalkyl, heterocycloalkyl and heterocyclic groups shown in the above-mentioned examples can be used. The preferred specific examples, the types and numbers of substituents are also the same.

[0103] Examples of the epoxy compound satisfying the above conditions include ethylene oxide, 1,2-epoxystyrene, 1-chloro-2,3-epoxypropylene, and α,α′-epoxybibenzyl.

[0104] [Fluorination reaction 5] (2E) Fluorination of aromatic compounds In the fluorination, a fluorine substituent is introduced into the aromatic ring, for example, by the following reaction: The fluorination of the aromatic ring of the phenol derivative or aniline derivative can be carried out by reducing it with a reducing agent such as zinc powder after the fluorination, thereby obtaining the target fluoride.

[0105] [Fluorination Reaction 5-1] Fluorination of Phenylhydrazine Derivatives The phenylhydrazine residue which may have one or more substituents may be substituted with a fluorine atom.

[0106] In the formula, R 5a , R 5b , R 5c , R 5d and R 5e The same or different groups represent a hydrogen atom, an alkyl group which may have one or more substituents, an aralkyl group which may have one or more substituents, an aryl group which may have one or more substituents, an alkoxy group which may have one or more substituents, a nitro group, a cyano group, a halogen atom, an acyl group, an arylcarbonyl group which may have one or more substituents, an amino group, a monoalkylamino group which may have one or more substituents, a dialkylamino group which may have one or more substituents, an acylamino group which may have one or more substituents, an arylcarbonylamino group which may have one or more substituents, or an alkylthio group which may have one or more substituents.

[0107] In the fluorination reaction 5-1, as R 5a , R 5b , R 5c, R 5d and R 5e The alkyl group, aralkyl group, aryl group, alkoxy group, acyl group, monoalkylamino group, dialkylamino group and acylamino group shown in the figure may be the same as those described above. The preferred specific examples, the types and the number of substituents are also the same.

[0108] In the fluorination reaction 5-1, as R 5a , R 5b , R 5c , R 5d and R 5e Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.

[0109] In the fluorination reaction 5-1, as R 5a , R 5b , R 5c , R 5d and R 5e The aryl group in the arylcarbonyl group shown in the formula (a) may be the same as the above-mentioned group. The preferred specific examples, the types and the number of substituents are also the same.

[0110] In the fluorination reaction 5-1, as R 5a , R 5b , R 5c , R 5d and R 5e The arylcarbonyl group in the arylcarbonylamino group shown above can be the same as those described above. Preferred specific examples, types and numbers of substituents are also the same.

[0111] In the fluorination reaction 5-1, as R 5a , R 5b , R 5c , R 5d and R 5e The alkylthio group shown in the formula (a) includes, for example, -S-(C1-C6 alkyl) and the like. The C1-C6 alkyl group may be the above-mentioned groups. Preferred specific examples, types and numbers of substituents are also the same.

[0112] [Fluorination Reaction 5-2] Fluorination of Phenol Derivatives The phenol derivative is formed into a difluorinated quinoid structure shown below by using IF5, and then reduced to produce a phenol derivative having fluorine introduced at the ortho-position or para-position.

[0113] In the formula, R 5a , R 5b , R 5c and R 5dThe same or different groups represent a hydrogen atom, an alkyl group which may have one or more substituents, an aralkyl group which may have one or more substituents, an aryl group which may have one or more substituents, an alkoxy group which may have one or more substituents, a nitro group, a cyano group, a halogen atom, an acyl group, an arylcarbonyl group which may have one or more substituents, an amino group, a monoalkylamino group which may have one or more substituents, a dialkylamino group which may have one or more substituents, an acylamino group which may have one or more substituents, an arylcarbonylamino group which may have one or more substituents, or an alkylthio group which may have one or more substituents.

[0114] In the fluorination reaction 5-2, as R 5a , R 5b , R 5c , R 5d and R 5e The alkyl group, aralkyl group, aryl group, alkoxy group, halogen atom, acyl group, arylcarbonyl group, monoalkylamino group, dialkylamino group, acylamino group, arylcarbonylamino group and alkylthio group shown in the figure may be the same as those described above. Preferred specific examples, types and numbers of substituents are also the same.

[0115] In the starting material in which both the ortho and para positions are substituted, a fluorine atom is introduced into the ortho or para position to generate a fluorinated quinone-type compound.

[0116] In the above examples, phenol which may have one or more substituents is used as the phenol derivative, but fluorine atoms may be introduced similarly into benzene-based aromatic compounds or condensed polycyclic hydrocarbons which have electron-donating groups such as hydroxyl groups or alkoxy groups and may be further substituted.

[0117] [Fluorination Reaction 5-3] Fluorination of 2-naphthol derivatives The 1-position of the naphthol can be monofluorinated or difluorinated.

[0118] In the formula, R 5a , R 5b , R 5c , R 5d , R 5e , R 5f and R 5g The same or different groups represent a hydrogen atom, an alkyl group which may have one or more substituents, an aralkyl group which may have one or more substituents, an aryl group which may have one or more substituents, an alkoxy group which may have one or more substituents, a nitro group, a cyano group, a halogen atom, an acyl group, an arylcarbonyl group which may have one or more substituents, an amino group, a monoalkylamino group, a dialkylamino group, an acylamino group, an arylcarbonylamino group, or an alkylthio group which may have one or more substituents.

[0119] In the fluorination reaction 5-3, as R 5a , R 5b , R 5c , R 5d , R 5e , R 5f and R 5g The alkyl group, aralkyl group, aryl group, alkoxy group, halogen atom, acyl group, arylcarbonyl group, monoalkylamino group, dialkylamino group, acylamino group, arylcarbonylamino group and alkylthio group shown in the figure may be the same as those described above. Preferred specific examples, types and numbers of substituents are also the same.

[0120] [Fluorination Reaction 5-4] Fluorination of Aniline Derivatives Aniline derivatives, like phenol derivatives, are also converted into a difluorinated quinoid structure shown below by IF5, and then reduced to generate aniline derivatives having fluorine introduced at the ortho-position or para-position.

[0121] In the formula, R 5a , R 5b , R 5c and R 5d The same or different groups represent a hydrogen atom, an alkyl group which may have one or more substituents, an aralkyl group which may have one or more substituents, an aryl group which may have one or more substituents, an alkoxy group which may have one or more substituents, a nitro group, a cyano group, a halogen atom, an acyl group, an arylcarbonyl group which may have one or more substituents, an amino group, a monoalkylamino group, a dialkylamino group, an acylamino group, an arylcarbonylamino group, or an alkylthio group which may have one or more substituents.

[0122] In the fluorination reaction 5-4, as R 5a , R 5b , R 5c , R 5d and R 5e The alkyl group, aralkyl group, aryl group, alkoxy group, halogen atom, acyl group, arylcarbonyl group, monoalkylamino group, dialkylamino group, acylamino group, arylcarbonylamino group and alkylthio group shown in the figure may be the same as those described above. Preferred specific examples, types and numbers of substituents are also the same.

[0123] As the aniline derivative, fluorine atoms may be introduced into the aromatic ring of aniline which may have one or more substituents and naphthylamine which may have one or more substituents.

[0124] [Fluorination reaction 6] (2F) Thiocarbonyl compounds (including thioketones, thioesters, thiocarbonates, thioamides, dithiocarboxylates, Fluorination of thiocarboxylates, dithiocarbamates, etc. This reaction is a reaction for fluorinating a compound having a partial structure: -C(=S)-Y- [wherein Y represents O, S or a single bond], and for example, the following reaction can be performed.

[0125] In the formula, R 6 and R 6a are the same or different and represent a hydrogen atom, an alkyl group which may have one or more substituents, an aralkyl group which may have one or more substituents, an aryl group which may have one or more substituents, an alkenyl group which may have one or more substituents, a cycloalkyl group which may have one or more substituents, a heterocycloalkyl group which may have one or more substituents, a heterocyclic group which may have one or more substituents, an alkoxy group which may have one or more substituents, an aryloxy group which may have one or more substituents, a monoalkylamino group which may have one or more substituents, a dialkylamino group which may have one or more substituents, an acyl group, an acylamino group, or R 6 and R 6a They may also be bonded to each other to form a ring structure.

[0126] R 6b It represents an alkyl group which may have one or more substituents, an aralkyl group which may have one or more substituents, an aryl group which may have one or more substituents, an alkenyl group which may have one or more substituents, a cycloalkyl group which may have one or more substituents, a heterocycloalkyl group which may have one or more substituents, or a heterocyclic group which may have one or more substituents.

[0127] In fluorination reaction 6, as R 6 , R 6a and R 6b The alkyl, aralkyl, aryl, alkenyl, cycloalkyl, heterocycloalkyl and heterocyclic groups shown in the above-mentioned examples can be used. The preferred specific examples, the types and numbers of substituents are also the same.

[0128] In fluorination reaction 6, as R 6 and R 6a The alkoxy group, aryloxy group, monoalkylamino group, dialkylamino group, acyl group and acylamino group shown in the formula may be the same as those described above, and the preferred specific examples, types and numbers of substituents are also the same.

[0129] In fluorination reaction 6, as R 6 and R 6a The cyclic structure that can be formed together can adopt the above-mentioned structure. The preferred specific examples, types and numbers of substituents are also the same.

[0130] When the amount of the fluorinating agent used in the reaction of formula (b) of fluorination reaction 6 is reduced (for example, 0.5 equivalent or less), R 6 -CF2-SR 6b The amount of production is dominant.

[0131] Examples of the thiocarbonyl compound satisfying the above conditions include O-(4-isopropylphenyl) S-methyl dithiocarbonate, O-(4-bromophenyl) S-methyl dithiocarbonate, ethyl 4-(((methylthio)thiocarbonyl)oxy)benzoate, O-decyl S-methyl dithiocarbonate, O-(3-phenylpropyl) S-methyl dithiocarbonate, O-methyl cyclohexanethiocarboxylate, 1-piperidinylthiocarboxylate, O-propyl dithiobenzoate, methyl dithiobenzoate, thiobenzophenone, O-phenyl thiobenzoate, N,N-dimethylphenylthioamide, ethyl 3-quinolinedithiocarboxylate, trifluoromethanethiocarbonylnaphthalene, N-methyl-N-phenyltrifluoromethanethioamide, N-benzyl-N-phenylheptafluoropropanethioamide, O-(4'-pentyl-[1,1'-bis(cyclohexane)]-4-yl) S-methyl dithiocarbonate, wait.

[0132] [Fluorination Reaction 7] (2G) Polyfluorination of the Ethyl Moiety of an Ethyl Sulfide Compound Having a -COOR Group In this fluorination, the ethyl moiety adjacent to the S atom is polyfluorinated.

[0133] For example, the reaction is carried out according to the following reaction formula.

[0134] R 7 -S-CH (COOR 7a )-CH3→R 7 -S-CHF-CF2-COOR 7a In the formula, R 7 It represents an aryl group which may have one or more substituents, or an aromatic heterocyclic group which may have one or more substituents.

[0135] R 7arepresents a hydrogen atom, an alkyl group which may have one or more substituents, an aralkyl group which may have one or more substituents, an aryl group which may have one or more substituents, an alkenyl group which may have one or more substituents, a cycloalkyl group which may have one or more substituents, a heterocycloalkyl group which may have one or more substituents, a heterocyclic group which may have one or more substituents, an alkoxy group which may have one or more substituents, an aryloxy group which may have one or more substituents, an amino group, a monoalkylamino group which may have one or more substituents, a dialkylamino group which may have one or more substituents, an acyl group, an acylamino group, a cyano group, an alkylsulfinyl group which may have one or more substituents, and a an aralkylsulfinyl group having one or more substituents, an arylsulfinyl group which may have one or more substituents, a cycloalkylsulfinyl group which may have one or more substituents, a heterocycloalkylsulfinyl group which may have one or more substituents, a sulfinyl group which may have one or more substituents and is bonded to a heterocyclic group, an alkylsulfonyl group which may have one or more substituents, an aralkylsulfonyl group which may have one or more substituents, an arylsulfonyl group which may have one or more substituents, a cycloalkylsulfonyl group which may have one or more substituents, a heterocycloalkylsulfonyl group which may have one or more substituents, or a sulfonyl group which may have one or more substituents and is bonded to a heterocyclic group.

[0136] In the fluorination reaction 7, as R 7 and R 7a The aryl group shown in : may be the same as the above-mentioned group. Preferred specific examples, types and numbers of substituents are also the same.

[0137] In the fluorination reaction 7, as R 7a The alkyl, aralkyl, alkenyl, cycloalkyl, heterocycloalkyl, heterocyclic, alkoxy, aryloxy, monoalkylamino, dialkylamino, acyl, acylamino, alkylsulfinyl, aralkylsulfinyl, arylsulfinyl, cycloalkylsulfinyl, heterocycloalkylsulfinyl, sulfinyl bonded with a heterocyclic group, alkylsulfonyl, aralkylsulfonyl, arylsulfonyl, cycloalkylsulfonyl, heterocycloalkylsulfonyl, and sulfonyl bonded with a heterocyclic group may be the same as those described above. Preferred specific examples, types, and numbers of substituents are also the same.

[0138] Examples of the ethyl sulfide compound having a -COOR group that satisfies the above conditions include ethyl 2-((4-chlorophenyl)thio)propionate.

[0139] [Fluorination reaction 8] (2H) Fluorination of unsaturated carbon compounds In this fluorination, fluorine and iodine are added to a carbon-carbon double bond or a carbon-carbon triple bond.

[0140] For example, the reaction is carried out according to the following reaction formula.

[0141] (a) R 8a R 8a’ C=CR 8b R 8b’ → FR 8a C-CR 8b I (b) R 8a C≡CR 8b → FR 8a C=CR 8b I In the formula, R 8a , R 8a’ , R 8b and R 8b’ are the same or different and represent a hydrogen atom, an alkyl group which may have one or more substituents, an aralkyl group which may have one or more substituents, an aryl group which may have one or more substituents, an alkenyl group which may have one or more substituents, an acyl group, a cycloalkyl group which may have one or more substituents, a heterocycloalkyl group which may have one or more substituents, an ester group or a halogen atom, or R 8a , R 8a’ , R 8b and R 8b’ Two or more of them may be bonded to each other to form a ring structure.

[0142] In the fluorination reaction 8, as R 8a , R 8a’ , R 8b and R 8b’ The alkyl group, aralkyl group, aryl group, alkenyl group, acyl group, cycloalkyl group, heterocycloalkyl group and halogen atom shown in the figure may be the same as those described above. The preferred specific examples, the types and numbers of substituents are also the same.

[0143] In the fluorination reaction 8, as R 8a , R 8a’ , R 8b and R 8b’ The cyclic structure that can be formed by two or more of the above-mentioned structures can be used together. The preferred specific examples, the types and numbers of the substituents are also the same.

[0144] In the fluorination reaction 8, as R 8a , R 8a’ , R 8b and R 8b’ Examples of the ester group include acyl-O-group and alkoxy-CO-group. As "acyl" and "alkoxy", the above-mentioned "acyl" and "alkoxy" can be used. Preferred specific examples, types and numbers of substituents are also the same.

[0145] Examples of unsaturated carbon compounds that satisfy the above conditions include C2-C4-C6 ... 20 Unsaturated carbon compounds, etc.

[0146] In the manufacturing method of the present invention, the amount of the organic compound used as the reaction substrate is not particularly limited. From the viewpoints of the conversion rate of the reaction, the selectivity of the target product, the yield, the efficiency of the initial stage of the reaction, etc., it is preferably 0.1 to 100 moles, more preferably 0.1 to 50 moles, further preferably 0.1 to 15 moles, and particularly preferably 0.1 to 10 moles relative to 1L of the organic solvent that can be used in the reaction. Since the IF5 used in the present invention is a strong oxidant, it is predicted that the decomposition products will also increase when the amount of the organic compound is increased, and it is inferred that the selectivity will decrease, so it is predicted that the yield will also decrease. Nevertheless, in the present invention, even if the amount of the organic compound is increased, it is easy to obtain the target product with a high yield, and it is easy to react efficiently from the initial stage of the reaction.

[0147] (2-2) Fluorinated composition (composition of the present invention) The fluorinated composition used in the production method of the present invention contains IF5, iodine (I2) and an amine, and contains 0.12 mol or less of the iodine relative to 1 mol of the IF5. The fluorinated composition is the composition of the present invention, and therefore the following description is also common to the composition of the present invention.

[0148] Although such a fluorinated composition (composition of the present invention) may be solid, a liquid composition is preferred from the viewpoints of reaction conversion, selectivity of the target product, yield, efficiency in the initial stage of the reaction, economic efficiency, and the like.

[0149] This fluorinated composition (composition of the present invention) can be used in the above-mentioned production method of the present invention, and its details can be understood based on technical common sense by referring to the description of the above-mentioned production method of the present invention in addition to the following description.

[0150] IF5 In the production method of the present invention, IF5 can form a complex with at least one selected from the group consisting of an amine described below, an acid described below, and a base other than an amine described below. In the case where a complex is formed, or in the case where a complex is not formed, a fluorinated organic compound can be efficiently synthesized.

[0151] In the manufacturing method of the present invention, the amount of IF5 used is not particularly limited. From the viewpoints of the conversion rate of the reaction, the selectivity of the target, the yield, the efficiency of the initial stage of the reaction, etc., it is preferably 0.1 to 100 moles, more preferably 0.1 to 50 moles, and further preferably 0.1 to 15 moles relative to 1L of the organic solvent that can be used in the reaction. Since the IF5 used in the present invention is a strong oxidant, it is predicted that the decomposed products will also increase when the amount of IF5 is increased according to technical common sense, and it is inferred that the selectivity will decrease, so it is predicted that the yield will also decrease, and the efficiency of the initial stage of the reaction will also decrease. Nevertheless, in the present invention, even if the amount of IF5 is increased, it is easy to obtain the target with a high yield, and it is easy to react efficiently from the initial stage of the reaction.

[0152] In the production method of the present invention, the amount of IF5 used is not particularly limited. From the viewpoints of reaction conversion rate, selectivity of the target product, yield, efficiency in the initial stage of the reaction, etc., it is preferably 0.1 to 10.0 mol, more preferably 0.3 to 5.0 mol, and further preferably 0.5 to 3.0 mol relative to 1 mol of the organic compound serving as the reaction substrate.

[0153] iodine In the production method of the present invention, when fluorinating an organic compound, iodine (I2) is used in a small amount instead of a large amount, thereby improving the reaction conversion rate, target selectivity, yield, etc., and the reaction can be efficiently carried out from the initial stage of the reaction, so the reaction can be completed in a short time, and the reaction can be carried out efficiently. In particular, when iodine (I2) is used in a large amount, the reaction substrate and iodine (I2) react to generate a considerable amount of iodide as a by-product, and the selectivity, yield, and efficiency of the initial stage of the reaction are reduced. However, in the present invention, since iodine (I2) is used in a small amount, iodide as a by-product is almost not generated, and the reaction conversion rate, target selectivity, yield, and efficiency of the initial stage of the reaction can be improved.

[0154] In the production method of the present invention, the amount of iodine (I2) used is 0.12 mol or less, preferably 0.11 mol or less, more preferably 0.10 mol or less, further preferably 0.05 mol or less, and particularly preferably 0.01 mol or less, relative to 1 mol of IF5. When the amount of iodine (I2) used exceeds 0.12 mol relative to 1 mol of IF5, the reaction substrate and iodine (I2) react to generate a considerable amount of iodide by-products, and the selectivity and yield of the target product decrease, and the reaction cannot be carried out in the initial stage of the reaction. In addition, in the production method of the present invention, there is no particular restriction on the lower limit of the amount of iodine (I2) used. Even in a very small amount, the selectivity and yield of the target product are high, and the reaction rate is fast. The lower limit of the amount of iodine (I2) used is usually 1.0×10 -10 Moore or so.

[0155] In the production method of the present invention, the amount of iodine (I2) used is not particularly limited. From the viewpoint of easily suppressing the reaction between the reaction substrate and iodine (I2) to form a byproduct of iodide, easily improving the reaction conversion rate, the selectivity and yield of the target product, the efficiency of the initial stage of the reaction, etc., the amount of iodine (I2) used is preferably 1.0×10 -10 ~0.12 mol, more preferably 5.0×10 -10 ~0.11 mol, more preferably 1.0×10 -9 ~0.10 mol, particularly preferably 5.0×10 -9 ~0.05 mol, more preferably 1.0×10 -8 ~0.01 mol.

[0156] amine Examples of the amine include: Aliphatic amines (aliphatic primary amines, aliphatic secondary amines, aliphatic tertiary amines), alicyclic amines (alicyclic secondary amines, alicyclic tertiary amines), aromatic amines (aromatic primary amines, aromatic secondary amines, aromatic tertiary amines), heterocyclic amines, etc.; Polymer-supported amines such as polyallylamine and polyvinylpyridine.

[0157] Examples of the aliphatic primary amine include methylamine, ethylamine, propylamine, butylamine, pentylamine, hexylamine, cyclohexylamine, and ethylenediamine.

[0158] Examples of the aliphatic secondary amine include dimethylamine, diethylamine, dipropylamine, dibutylamine, dipentylamine, dihexylamine, and dicyclohexylamine.

[0159] Examples of the aliphatic tertiary amine include trimethylamine, triethylamine, diisopropylethylamine, and N,N,N′,N′-tetramethylethylenediamine.

[0160] Examples of the alicyclic secondary amine include piperidine, piperazine, pyrrolidine, and morpholine.

[0161] Examples of the alicyclic tertiary amine include N-methylpiperazine, N-methylpyrrolidine, 5-diazabicyclo[4.3.0]non-5-ene, and 1,4-diazabicyclo[2.2.2]octane.

[0162] Examples of the aromatic amine include aniline, methylaniline, dimethylaniline, N,N-dimethylaniline, halogenated aniline, and nitroaniline.

[0163] Examples of the heterocyclic amine include one or more of pyridine, pyrimidine, piperazine, quinoline, and imidazole.

[0164] Among them, from the viewpoints of reaction conversion rate, selectivity of the target product, yield, efficiency in the initial stage of the reaction, etc., preferred are aliphatic amines, alicyclic amines, aromatic amines, heterocyclic amines, polymer-supported amines, etc., more preferred are aliphatic amines, further preferred are aliphatic tertiary amines, particularly preferred are triethylamine, pyridine, etc., and most preferred is triethylamine.

[0165] In the production method of the present invention, the amount of amine used is not particularly limited. From the viewpoints of reaction conversion rate, selectivity of the target product, yield, efficiency in the initial stage of the reaction, etc., the content of the amine in the fluorination composition (composition of the present invention) is preferably 0.5 to 20 mol, more preferably 0.8 to 10 mol, and even more preferably 0.9 to 5 mol, relative to 1 mol of IF5.

[0166] In the production method of the present invention, the amount of amine used is not particularly limited. From the viewpoints of reaction conversion rate, selectivity of the target product, yield, efficiency in the initial stage of the reaction, etc., it is preferably 0.1 to 10.0 mol, more preferably 0.3 to 5.0 mol, and even more preferably 0.5 to 3.0 mol relative to 1 mol of the organic compound as the reaction substrate.

[0167] acid The production method of the present invention is carried out using the above-mentioned fluorination composition (composition of the present invention). From the viewpoints of reaction conversion rate, selectivity of the target product, yield, efficiency in the initial stage of the reaction, etc., the fluorination composition (composition of the present invention) preferably further contains an acid.

[0168] From the viewpoints of reaction conversion rate, selectivity of the target product, yield, efficiency in the initial stage of the reaction, etc., the acid is preferably a Bronsted acid, a Lewis acid, or a combination thereof, and more preferably a Bronsted acid.

[0169] In addition, a Lewis acid may refer to a substance that is not an acid according to the Bronsted definition but is an acid according to the Lewis definition.

[0170] Specific examples of the acid include: Sulfuric acid, nitric acid, phosphoric acid, polyphosphoric acid, hydrogen fluoride (HF), hydrofluoric acid, hydrogen chloride, hydrochloric acid, hydrogen bromide, hydrogen iodide, hypochlorous acid, chlorous acid, chloric acid, perchloric acid, perbromic acid, periodic acid and other hydrogen halides, hydrohalic acids, hypohalous acids, halous acids, halogen acids, perhalogen acids, etc.; Fluorosulfonic acid, chlorosulfonic acid, methanesulfonic acid, ethanesulfonic acid, trifluoromethanesulfonic acid, difluoromethanesulfonic acid, trichloromethanesulfonic acid, perfluorobutanesulfonic acid, perfluorooctanesulfonic acid, benzenesulfonic acid, toluenesulfonic acid, nitrobenzenesulfonic acid and other sulfonic acids, polystyrenesulfonic acid, etc.; Fluorinated sulfonic acid resin (Nafion-H) and other polymers supporting sulfonic acid; Formic acid, acetic acid, propionic acid, chloroacetic acid, bromoacetic acid, dichloroacetic acid, trichloroacetic acid, trifluoroacetic acid, glycolic acid, lactic acid, benzoic acid, oxalic acid, succinic acid and other monocarboxylic acids or polycarboxylic acids; Lewis acids such as SO3, BF3, BCl3, B(OCH3)3, AlCl3, AlBr3, SbF3, SbCl3, SbF5, PF3, PF5, AsF3, AsCl3, AsF5, TiCl4, NbF5, TaF5 or their ether coordination compounds; Acids formed from Lewis acids and hydrogen halides such as HBF4, HPF6, HAsF6, HSbF6, HSbCl6, or coordination compounds with their ethers, etc.; or A mixture of two or more of these.

[0171] The acid may also be supported by a carrier.

[0172] Examples of the carrier include SiO2, methylated SiO2, Al2O3, Al2O3-WB, MoO3, ThO2, ZrO2, TiO2, Cr2O3, SiO2-Al2O3, SiO2-TiO2, SiO2-ZrO2, TiO2-ZrO2, Al2O3-B2O3, SiO2-WO3, SiO2-NH4F, HSO3Cl-Al2O3, HF-NH4-Y, HF-Al2O3, NH4F-SiO2-Al2O3, AlF3-Al2O3, Ru-F-Al2O3, F-Al2O3, KF-Al2O3, AlPO4, AlF3, bauxite, kaolin, activated carbon, graphite, Pt-graphite, ion exchange resin, metal sulfates, chlorides, metals (e.g. Al, etc.), alloys (e.g. Al-Mg, Ni-Mo, etc.) and polymers (e.g. polystyrene, etc.), etc.

[0173] The acid preferably contains HF from the viewpoints of reaction conversion rate, selectivity of the target product, yield, efficiency in the initial stage of the reaction, etc. The fluorination composition used in the production method of the present invention (composition of the present invention) preferably contains HF in addition to IF5, iodine and amine.

[0174] The amount of the acid is not particularly limited, but is preferably 0.5 to 20 mol, more preferably 0.8 to 10 mol, and even more preferably 0.9 to 5 mol relative to 1 mol of IF5 from the viewpoints of reaction conversion, target product selectivity, yield, initial reaction efficiency, etc.

[0175] In the production method of the present invention, the amount of the acid used is not particularly limited. From the viewpoints of reaction conversion rate, selectivity of the target product, yield, efficiency in the initial stage of the reaction, etc., it is preferably 0.5 to 20 mol, more preferably 0.8 to 10 mol, and even more preferably 0.9 to 5.0 mol relative to 1 mol of the organic compound as the reaction substrate.

[0176] Bases other than amines The production method of the present invention is carried out using the above-mentioned fluorination composition (composition of the present invention), and may further contain a base other than amine.

[0177] Examples of bases other than amines include: Alkali metal or alkaline earth metal hydroxides such as sodium hydroxide, potassium hydroxide, lithium hydroxide, rubidium hydroxide, cesium hydroxide, magnesium hydroxide, calcium hydroxide, barium hydroxide, etc.; Alkali metal alkoxides such as sodium methoxide, sodium ethoxide, sodium butoxide, potassium methoxide, potassium ethoxide, potassium butoxide, lithium methoxide and lithium ethoxide; Alkali metal or alkaline earth metal hydrides such as sodium hydride, potassium hydride, lithium hydride, calcium hydride, etc.; Alkali metals such as sodium, potassium, and lithium; Alkaline earth metal oxides such as magnesium oxide and calcium oxide; One or more of ammonia, ammonium hydroxide, tetramethylammonium hydroxide, tetraethylammonium hydroxide, tetrabutylammonium hydroxide, octyltriethylammonium hydroxide, benzyltrimethylammonium hydroxide and other ammonium hydroxide salts or polymer-supported ammonium hydroxide salts (for example, AMBERLITE resin, etc.).

[0178] In the production method of the present invention, when a base other than an amine is used, the amount of the base other than an amine used is not particularly limited. From the viewpoints of the conversion rate of the reaction, the selectivity of the target product, the yield, the efficiency in the initial stage of the reaction, etc., the content of the base other than an amine in the fluorination composition (the composition of the present invention) is preferably 0.5 to 20 mol, more preferably 0.8 to 10 mol, and even more preferably 0.9 to 5 mol, relative to 1 mol of IF5.

[0179] In the production method of the present invention, the amount of the base other than the amine used is not particularly limited. From the viewpoints of the conversion rate of the reaction, the selectivity of the target product, the yield, the efficiency of the initial stage of the reaction, etc., it is preferably 0.1 to 10.0 mol, more preferably 0.3 to 5.0 mol, and even more preferably 0.5 to 3.0 mol relative to 1 mol of the organic compound as the reaction substrate.

[0180] Salt The above-mentioned acids may form salts with the above-mentioned amines and / or bases other than amines.

[0181] Examples of the "salt" include: Metal or ammonium salts of sulfuric acid or sulfonic acid such as sodium sulfate, sodium hydrogen sulfate, potassium sulfate, potassium hydrogen sulfate, lithium sulfate, cesium sulfate, calcium sulfate, magnesium sulfate, ammonium sulfate, triethylammonium sulfate, pyridinium sulfate, trimethylpyridinium sulfate, polyallylammonium sulfate, polyvinylpyridinium sulfate, sodium methanesulfonate, ammonium methanesulfonate, tetramethylammonium methanesulfonate, potassium ethanesulfonate, lithium butanesulfonate, sodium benzenesulfonate, sodium toluenesulfonate, sodium trifluoromethanesulfonate, and sodium polystyrenesulfonate; Metal salts or ammonium salts of carboxylic acids such as sodium formate, ammonium formate, sodium acetate, potassium acetate, lithium acetate, magnesium acetate, calcium acetate, ammonium acetate, methylammonium acetate, diethylammonium acetate, triethylammonium acetate, tetraethylammonium acetate, pyridinium acetate, sodium propionate, potassium propionate, sodium butyrate, polyallylammonium acetate, polyvinylpyridinium acetate, sodium isobutyrate, sodium valerate, sodium nonanoate, sodium chloroacetate, sodium bromoacetate, sodium trichloroacetate, sodium trifluoroacetate, sodium glycolate, sodium lactate, sodium benzoate, sodium oxalate, sodium succinate, and sodium polyacrylate; Metal halides such as LiBr, LiI, NaBr, NaI, KBr, KI, RbBr, RbI, CsBr, CsI, BeBr2, BeI2, MgBr2, MgI2, CaBr2, CaI2, SrBr2, SrI2, BaBr2, BaI2, ZnBr2, ZnI2, CuBr2, CuI2, CuBr, CuI, AgBr, AgI, AuBr, AuI, NiBr2, NiI2, PdBr2, PdI2, PtBr2, PtI2, CoBr2, Col2, FeBr2, FeBr3, FeI2, FeI3, MnBr2, MnI2, CrBr2, CrI2, PbBr2, PbI2, SnBr2, SnI2, SnBr4, SnI4; NH4Br, NH4I, MeNH3Br, MeNH3I, Me4NBr, Me4NI, Et4NBr, Et4NI, Bu4NBr, Bu4NI, PhMe3NBr, PhMe3NI, PhCH2NMe3I, pyridinium bromide, pyridinium iodide, chloropyridinium iodide, methylpyridinium iodide, cyanopyridinium iodide, bipyridinium iodide, quinolinium iodide, isoquinolinium iodide, N-methylpyridinium bromide, N-methylpyridinium iodide, N-methylquinolinium iodide and other pyridinium halides or ammonium halides (Me represents methyl, Et represents ethyl, Bu represents n-butyl, and Ph represents phenyl); Phosphonium salts such as Me4PF, Me4PBr, Me4PI, Et4PI, Pr4I, Bu4PBr, Bu4PI, Ph4PF, Ph4PBr, Ph4PI and tetramethylphosphonium acetate (Me represents methyl, Et represents ethyl, Pr represents n-propyl, Bu represents n-butyl and Ph represents phenyl); Sodium fluoride, potassium fluoride, cesium fluoride, ammonium fluoride, tetraethylammonium fluoride, tetrabutylammonium fluoride, polyallylammonium fluoride, sodium chloride, ammonium chloride, sodium hypochlorite, sodium chlorite, sodium chlorate, sodium perchlorate, sodium perbromate, sodium periodate and other hydrogen halides, hypohalous acids, halous acids, halogen acids or perhalogen acids, metal salts or amine salts; Metal carbonates such as sodium carbonate, potassium carbonate, lithium carbonate, sodium bicarbonate, potassium bicarbonate, lithium bicarbonate, calcium carbonate, magnesium carbonate, etc.; Phosphate metal salts or amine phosphates such as sodium phosphate, potassium phosphate, sodium hydrogen phosphate, sodium dihydrogen phosphate, ammonium phosphate, and pyridinium phosphate; Metal nitrates or amine nitrates such as sodium nitrate, potassium nitrate, ammonium nitrate and pyridinium nitrate; Metal salts or amine salts formed by Lewis acids and hydrogen halides, such as NaBF4, KBF4, LiBF4, NaSbF6, NaAsF6, NaPF6, NH4BF4, NH4SbF6, NH4PF6; (C2H5)4NF, 1-ethyl-3-methylimidazolium fluoride, (C2H5)3N-(HF) n 、(C2H5)4NF-(HF) n , (n-C4H9)3N-(HF) n , (n-C4H9)4NF-(HF) n 、BF3·Et2O-(HF) n Room temperature molten salts having fluorine anions or HF, etc. (n=1 to 20) (Et represents ethyl).

[0182] The "salt" may be a single species or a mixture or combination of two or more species.

[0183] The amount of the salt used can be determined based on the amounts of the amine, acid, and base other than the amine described above, and can be adjusted appropriately.

[0184] Other additives Furthermore, the fluorinated composition (the composition of the present invention) may contain additives such as halogens other than iodine, interhalogen compounds, and polyhalides, as desired.

[0185] Examples of the “halogen other than iodine” include bromine and chlorine. Among them, bromine is preferred from the viewpoints of reaction conversion rate, selectivity and yield of the target product, efficiency in the initial stage of the reaction, and the like.

[0186] The above-mentioned "interhalogen compound" refers to an interhalogen compound other than IF5, and examples thereof include ClF, BrF, ICl, IBr, I2Cl6, and ICl3.

[0187] Examples of the “polyhalide” include LiCl4I, NaCl4I, KCl4I, CsCl4I, RbCl4I, Me4NCl4I, Et4NCl4I, Pr4NCl4I, Bu4NCl4I, PhNMe3Cl4I, PhCH2NMe3Cl4I, Me3SCl4I, Cl8IP, KCl3I2, Me4NCl3I2, 2,2'-bipyridiniumμ-chlorodichlorodiiodide, 2,2'-biquinoliniumμ-chlorodichlorodiodide, iiodate), KCl2I, Me4NCl2I, Me4NClI2, Et4NCl3, Ph4AsCl3, KClF2, Me4NClF4, CsClF4, CsCl3FI, KBrClI, NH4BrClI, Me4NBrClI, Me4NBrCl2, Bu4NBrCl2, Me4N BrCl2I2, CsBrFI, NaBrF2, KBrF2, CsBrF4, Me4NBrF4, CsBrF6, Me4NBrF6, Et4NBr6Cl, CsBr3, Me4NBr3, Et4Br3, Bu4NBr3, PhCH2NMe3Br3, pyridinium tribromide (pyridinium tribromide), Br7P, CsBrI2, Me4NBrI2, Me4NBrI4, Me4NBrI6, KBr2Cl, Me4NBr2Cl, Bu4NBr2Cl, KBr2I, Me4NBr2I, Bu4NBr2I, 2,2'-bipyridinium μ-bromodibromodiiodate, NaF2I, KF2I, CsF4I, CsF6I, CsF8I, KI3, CsI3, Me4NI3, Et4NI3, Pr4NI3, Bu4NI3, pyridinium triiodide triiodide), Me4NI5, Et4NI7, Me4NI9, Me4PBr3, Me4PI3, Me4PIBr2, Me4PICl2, Et4PI3, Bu4PI3, Ph4PI3, Ph4PBr3, Ph4PIBr2, etc. (Me represents methyl, Et represents ethyl, Pr represents n-propyl, Bu represents n-butyl, and Ph represents phenyl).

[0188] The "additive" may be a single type or a mixture or combination of two or more types.

[0189] When using the above-mentioned additive, its usage amount can be used within the scope of not damaging the effect of the present invention, and can be appropriately adjusted. But, when using the halogen other than iodine as additive, from the viewpoint of suppressing the generation of by-product as far as possible, its usage amount is preferably equal to or below the usage amount of the above-mentioned iodine.

[0190] Organic solvents Although the production method of the present invention does not exclude the possibility of carrying out the reaction in the absence of a solvent, it is preferred to carry out the reaction in the presence of an organic solvent from the viewpoints of the reaction conversion rate, the selectivity of the target product, the yield, the efficiency in the initial stage of the reaction, etc. That is, the fluorinated composition (the composition of the present invention) is preferably a liquid composition using an organic solvent.

[0191] From the viewpoints of selectivity and yield of the target product, efficiency in the initial stage of the reaction, and the like, the organic solvent is preferably an aprotic organic solvent.

[0192] Examples of the organic solvent preferably used in the production method of the present invention include, from the viewpoints of selectivity, yield, efficiency in the initial stage of the reaction, and the like, the following: Aliphatic solvents (aliphatic hydrocarbons) such as pentane, hexane, heptane, cyclohexane, petroleum ether, etc. Halogenated aliphatic solvents (halogenated hydrocarbons) such as dichloromethane, dichloroethane, chloroform, fluorotrichloromethane, 1,1,2-trichlorotrifluoroethane, 2-chloro-1,2-dibromo-1,1,2-trifluoroethane, 1,2-dibromohexafluoropropane, 1,2-dibromotetrafluoroethane, 1,1-difluorotetrachloroethane, 1,2-difluorotetrachloroethane, heptafluoro-2,3,3-trichlorobutane, 1,1,1,3-tetrachlorotetrafluoropropane, 1,1,1-trichloropentafluoropropane, 1,1,1-trichlorotrifluoroethane, and polychlorotrifluoroethylene; Ester solvents such as methyl formate, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, methyl propionate, γ-butyrolactone, and propylene carbonate; Nitrile solvents such as acetonitrile and propionitrile; Aromatic solvents (aromatic hydrocarbons) such as benzene, chlorobenzene, toluene, dichlorobenzene, fluorobenzene, and nitrobenzene; Ether solvents such as diethyl ether, dipropyl ether, tetrahydrofuran, cyclopentyl methyl ether (CPME) and methyl tert-butyl ether (MTBE); Ketone solvents such as acetone; Amide solvents such as N,N-dimethylformamide (DMF), N,N-diethylformamide, N,N-dimethylacetamide, 1-methyl-2-pyrrolidone, 1,3-dimethyl-2-imidazolidinone (DMI), tetramethyl urea, 1,3-dimethylpropylene urea, and hexamethylphosphoramide (HMPA); Dimethyl sulfoxide (DMSO); Nitromethane, etc.

[0193] These may be used alone or in combination of two or more thereof (eg, a mixed solvent).

[0194] Among them, from the viewpoints of reaction conversion rate, selectivity of the target product, yield, efficiency in the initial stage of the reaction, etc., preferred are aliphatic solvents, halogenated aliphatic solvents, ester solvents, nitrile solvents, aromatic solvents, ether solvents, ketone solvents, amide solvents, etc., more preferred are aliphatic solvents, halogenated aliphatic solvents, nitrile solvents, aromatic solvents, etc., and further preferred are halogenated aliphatic solvents, nitrile solvents, aromatic solvents, etc.

[0195] Reaction conditions, etc. The reaction temperature of fluorination in the production method of the present invention is not particularly limited, but is preferably -20 to 120°C, more preferably -10 to 100°C, further preferably 0 to 90°C, and particularly preferably 5 to 80°C, from the viewpoints of reaction conversion rate, selectivity of the target product, yield, efficiency in the initial stage of the reaction, and the like.

[0196] The reaction time of fluorination in the production method of the present invention may vary depending on the reaction substrate (organic compound), target product, etc., and is preferably, for example, 3 minutes to 80 hours, more preferably 5 minutes to 60 hours, further preferably 30 minutes to 40 hours, particularly preferably 1 to 30 hours, and most preferably 2 to 24 hours from the viewpoints of reaction conversion rate, selectivity of the target product, yield, efficiency in the initial stage of the reaction, and economic efficiency.

[0197] The atmosphere for carrying out the fluorination of the present invention is not particularly limited, but is preferably an inert gas atmosphere, such as nitrogen, helium, and argon.

[0198] The reaction pressure of the fluorination of the present invention is not particularly limited. From the perspectives of the conversion rate of the reaction, the selectivity of the target product, the yield, the efficiency of the initial stage of the reaction, the economy, etc., it is preferably 0 kPa or more, more preferably 10 kPa or more, further preferably 20 kPa or more, and particularly preferably 30 kPa or more. The upper limit of the reaction pressure is not particularly limited, and is usually about 2 MPa. In addition, in the present invention, when there is no special statement about pressure, it is a gauge pressure.

[0199] The reactor that can be used in the fluorination of the present invention has no particular limitation on shape and structure as long as it can withstand the above-mentioned temperature and pressure. Examples of the reactor include a vertical reactor, a horizontal reactor, and a multi-tubular reactor. Examples of the material of the reactor include stainless steel, iron, nickel, an iron-nickel alloy, Hastelloy, and a fluororesin.

[0200] After the fluorination reaction is completed, a purification treatment may be performed by a common method as needed to obtain a fluorinated organic compound.

[0201] The number (moles) of fluorine atoms introduced per 1 mole of the reaction substrate by the reaction of the present invention is not particularly limited, and may be, for example, 0.65 to 20 moles, 0.70 to 10 moles, 0.75 to 7 moles, 0.80 to 5 moles, etc.

[0202] Example Hereinafter, the features of the present invention will be clarified by describing examples, but the present invention is not limited to these examples.

[0203] In addition, in the following examples, the reactions were carried out under a nitrogen atmosphere.

[0204] The meanings of the symbols and abbreviations in the examples are as follows.

[0205] Et3N: triethylamine.

[0206] In the following examples, the iodine content in the fluorinated composition was quantitatively determined by the following method.

[0207] 1. Add the fluorinated composition (about 7 g) dropwise into ice water (30 g).

[0208] 2. Extract the iodine using chloroform.

[0209] 3. Wash the chloroform layer with sodium bicarbonate solution and water.

[0210] 4. Add 0.1 mol / L Na2S2O3 aqueous solution (15 g) to the chloroform layer and stir vigorously at room temperature for 10 minutes.

[0211] 5. Separate the water layer.

[0212] 6. After the aqueous layer is appropriately diluted with water, the iodine content is quantified in the form of iodide ions using ion chromatography.

[0213] The fluorinated composition in which iodine (66.0 mg, 0.26 mmol) was added to IF5-Et3N-3HF (1.0 g, 2.62 mmol) was quantified according to the above-mentioned procedure and found to be 65.8 mg, thereby confirming the reliability of the analytical method.

[0214] Example 1 After adding dichloromethane (4.0 mL) to the reactor, IF5-Et3N-3HF (460 mg, 1.2 mmol) and a dichloromethane dilution of iodine (1 mL, containing 0.0001 mg, 0.0000004 mmol as iodine) were added under stirring. Then, ethyl 3-oxobutanoate (130 mg, 1.0 mmol) was added and the reaction was carried out at room temperature. After 3 hours, F-NMR confirmed that 26% of ethyl 2-fluoro-3-oxobutanoate and 1% of ethyl 2-difluoro-3-oxobutanoate were generated.

[0215] Example 2 After adding dichloromethane (4.0 mL) to the reactor, IF5-Et3N-3HF (460 mg, 1.2 mmol) and iodine (1.5 mg, 0.0059 mmol) were added under stirring. Then, ethyl 3-oxobutanoate (130 mg, 1.0 mmol) was added and the reaction was carried out at room temperature. After 3 hours, F-NMR confirmed that 20% of ethyl 2-fluoro-3-oxobutanoate and 1% of ethyl 2-difluoro-3-oxobutanoate were generated.

[0216] Example 3 After adding dichloromethane (4.0 mL) to the reactor, IF5-Et3N-3HF (460 mg, 1.2 mmol) and iodine (15.2 mg, 0.06 mmol) were added under stirring. Then, ethyl 3-oxobutanoate (130 mg, 1.0 mmol) was added and the reaction was carried out at room temperature. After 3 hours, F-NMR confirmed that 18% of ethyl 2-fluoro-3-oxobutanoate and 2% of ethyl 2-difluoro-3-oxobutanoate were generated.

[0217] Example 4 After adding toluene (3.0 mL) to the reactor, IF5-Et3N-3HF (460 mg, 1.2 mmol) and a dichloromethane dilution of iodine (1 mL, containing 0.0001 mg, 0.0000004 mmol as iodine) were added under stirring. Then, O-n-decyl S-methyl dithiocarbonate (297.6 mg, 1.2 mmol) was added and the reaction was carried out at room temperature. After 10 hours, F-NMR confirmed that 20% of n-decyl trifluoromethyl ether (CF3) and 49% of methyln-decyloxydifluoromethyl sulfide (CF2) were generated.

[0218] Example 5 After adding toluene (3.0 mL) to the reactor, IF5-Et3N-3HF (460 mg, 1.2 mmol) and iodine (14.3 mg, 0.057 mmol) were added under stirring. Then, O-n-decyl S-methyl dithiocarbonate (297.6 mg, 1.2 mmol) was added and the reaction was carried out at room temperature. After 10 hours, F-NMR confirmed that 22% of n-decyl trifluoromethyl ether (CF3) and 51% of methyl n-decyloxydifluoromethyl sulfide (CF2) were generated.

[0219] Comparative Example 1 After adding dichloromethane (4.0 mL) to the reactor, IF5-Et3N-3HF (460 mg, 1.2 mmol) and iodine (151.8 mg, 0.6 mmol) were added under stirring. Then, ethyl 3-oxobutanoate (130 mg, 1.0 mmol) was added and the reaction was carried out at room temperature. After 3 hours, 0.1% of ethyl 2-fluoro-3-oxobutanoate was generated by F-NMR. Ethyl 2-difluoro-3-oxobutanoate was not generated.

[0220] Comparative Example 2 After adding dichloromethane (4.0 mL) to the reactor, IF5-Et3N-3HF (460 mg, 1.2 mmol) was added under stirring. Then, ethyl 3-oxobutanoate (130 mg, 1.0 mmol) was added and the reaction was carried out at room temperature. After 3 hours, F-NMR confirmed that 11% of ethyl 2-fluoro-3-oxobutanoate and 6% of ethyl 2-difluoro-3-oxobutanoate were generated.

[0221] Example 6 and Comparative Example 3 After adding monoglyme (1.0 mL) and acetonitrile (2.0 mL) to the reactor, IF5-Et3N-3HF (1264 mg, 3.3 mmol) and iodine (Example 6: 126 mg, 0.33 mmol, Comparative Example 3: not added) were added under stirring. Then, O-(3,4,5-trifluorophenyl)4''-butyl-2',3,5-trifluoro-[1,1':4',1''-terphenyl]-4-carbothioate (1.59 g, 3.0 mmol) was added and the reaction was carried out at 50°C. The yield of 4''-butyl-4-(difluoro(3,4,5-trifluorophenoxy)methyl)-2',3,5-trifluoro-1,1':4',1''-terphenyl at each time is shown in the following table. It was confirmed that the time until the reaction started could be shortened by adding iodine.

[0222] [Table 1] Yield at each time Comparative Example 4 After adding toluene (10.0 mL) to the reactor, IF5-Et3N-3HF (1.54 g, 4.03 mmol) was added under stirring. Then, O-n-decyl S-methyldithiocarbonate (1.0 g, 4.03 mmol) was added and the reaction was carried out at room temperature. After 10 hours, F-NMR confirmed that 5% of n-decyl trifluoromethyl ether (CF3) and 50% of methyl n-decyloxydifluoromethyl sulfide (CF2) were generated.

[0223] Industrial Applicability The present invention can provide a production method capable of efficiently synthesizing a fluorinated organic compound, a composition capable of efficiently fluorinating an organic compound, and the like.

Claims

1. A method for producing a fluorinated organic compound, characterized in that: The method comprises the step of fluorinating an organic compound in the presence of a fluorinating composition, The fluorinated composition contains IF5, iodine, and an amine, and contains 0.12 mol or less of the iodine relative to 1 mol of the IF5.

2. The manufacturing method according to claim 1, characterized in that: The iodine content is 0.11 mol or less relative to 1 mol of IF5.

3. The manufacturing method according to claim 1 or 2, characterized in that: The amine contains at least one amine selected from aliphatic amines, alicyclic amines, aromatic amines, heterocyclic amines and polymer-supported amines.

4. The manufacturing method according to any one of claims 1 to 3, characterized in that: The amine contains an aliphatic amine.

5. The manufacturing method according to claim 3 or 4, characterized in that: The aliphatic amine contains aliphatic tertiary amine.

6. The manufacturing method according to claim 5, characterized in that: The aliphatic tertiary amine contains triethylamine.

7. The manufacturing method according to any one of claims 1 to 6, characterized in that: The fluorinated composition also contains an acid.

8. The manufacturing method according to claim 7, characterized in that: The acid contains a Bronsted acid and / or a Lewis acid.

9. The manufacturing method according to claim 7 or 8, characterized in that: The acid contains HF.

10. A composition, characterized in that: Contains IF5, iodine and amine, and, The iodine is contained in an amount of 0.12 mol or less relative to 1 mol of the IF5.

11. The composition according to claim 10, characterized in that: The content of the iodine is 0.11 mol or less relative to 1 mol of the IF5.

12. The composition according to claim 10 or 11, characterized in that: The amine contains at least one amine selected from aliphatic amines, alicyclic amines, aromatic amines, heterocyclic amines and polymer-supported amines.

13. The composition according to any one of claims 10 to 12, characterized in that: The amine contains an aliphatic amine.

14. The composition according to claim 12 or 13, characterized in that: The aliphatic amine contains aliphatic tertiary amine.

15. The composition of claim 14, wherein: The aliphatic tertiary amine contains triethylamine.

16. The composition according to any one of claims 10 to 15, characterized in that: Also contains acid.

17. The composition of claim 16, wherein: The acid contains a Bronsted acid and / or a Lewis acid.

18. The composition according to claim 16 or 17, characterized in that: The acid contains HF.

19. A fluorination reagent for an organic compound, characterized in that: Contains IF5, iodine and amine, The iodine is contained in an amount of 0.12 mol or less relative to 1 mol of the IF5.

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