Method for producing fluorinated organic compound

Abstract

Provided is a novel method for producing a fluorinated organic compound that facilitates removal or separation of an auxiliary agent and that is advantageous in terms of production costs. The production method is a method for producing a difluoride which is a compound represented by formula (1) (in the formula, R1, R2, and n have the same definitions as the symbols described in the specification). The method involves a step for reacting the compound represented by formula (1) with (A) at least one fluorine source selected from hydrogen fluoride, hydrogen fluoride salts, and fluoride salts, (B) at least one iodine source selected from iodine and ammonium iodide, and (C) a compound having at least one fluorinated quaternary nitrogen atom in the molecule to difluorinate the compound represented by formula (1), wherein the amount of the iodine source (B) used is less than 1.0 mol with respect to 1 mol of the compound represented by formula (1).

Description

Method for producing fluorinated organic compounds

[0001] The present disclosure relates to methods for producing fluorinated organic compounds.

[0002] Fluorinated organic compounds are extremely important compounds for various chemical products such as functional materials, pharmaceutical and agricultural chemical compounds, and electronic materials, as well as intermediates thereof. For example, Non-Patent Document 1 discloses a method for producing fluorinated organic compounds by reacting a compound of the formula: CH in a solvent such as dichloroethane. ２ =CH-CH ２ A method for difluorinating an olefin represented by —R by reacting it with p-iodotoluene (catalyst), Selectfluor™ (1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate)), and an HF source has been proposed.

[0003] J. Am. Chem. Soc. 2016, 138, 5004-5007

[0004] An object of the present disclosure is to provide a novel method for producing a fluorinated organic compound, which allows for easy removal or separation of auxiliary agents and is advantageous in terms of production costs.

[0005] The present disclosure includes the following aspects: [Item 1] A compound represented by the following formula (1): (In the formula, R １ and R ２ are independently a hydrogen atom or an organic group, or may be taken together with two adjacent carbon atoms to form a ring, n is 1 or 2, and the symbol: is a double bond or a triple bond, provided that when the symbol is a triple bond, n is 1, when the symbol is a double bond, n is 2, and two R １ may be the same or different, and two R ２ may be the same or different from each other, or two R １ , or two R ２may each be taken together with an adjacent carbon atom to form a ring. A method for producing a difluoride of a compound represented by formula (1), comprising the step of reacting the compound represented by formula (1) with: (A) at least one fluorine source selected from hydrogen fluoride, a hydrogen fluoride salt, and a fluoride salt; (B) at least one iodine source selected from iodine and ammonium iodide; and (C) a compound having at least one fluorinated quaternary nitrogen atom in the molecule to difluorinate the compound represented by formula (1), wherein the amount of the iodine source (B) used is less than 1.0 mole per mole of the compound represented by formula (1). [Item 2] The method according to item 1, wherein the iodine source (B) is iodine. [Item 3] The method according to item 1 or 2, wherein the amount of the iodine source (B) used is 0.2 moles or less per mole of the compound represented by formula (1). [Item 4] The production method according to any one of Items 1 to 3, wherein compound (C) is at least one selected from 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2,2,2]octane bis(tetrafluoroborate), and N-fluoropyridinium salts and multimers thereof. [Item 5] The production method according to any one of Items 1 to 4, wherein compound (C) is 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2,2,2]octane bis(tetrafluoroborate). [Item 6] The production method according to any one of Items 1 to 5, wherein the amount of compound (C) used is within a range of 0.1 to 10 moles per mole of the compound represented by Formula (1). [Item 7] The production method according to any one of Items 1 to 6, wherein compound (C) is used in an amount such that the number of F atoms on N atoms in compound (C) exceeds 1 mole per mole of the compound represented by Formula (1). [Item 8] The production method according to any one of Items 1 to 7, wherein the fluorine source (A) is hydrogen fluoride. [Item 9] The production method according to any one of Items 1 to 8, wherein the amount of the fluorine source (A) used is within a range of 0.1 to 1,000 moles per mole of the compound represented by Formula (1).[Item 10] The production method according to any one of Items 1 to 9, wherein the fluorine source (A) is hydrogen fluoride, the iodine source (B) is iodine or tetrabutylammonium iodide, and the compound (C) is 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2,2,2]octane bis(tetrafluoroborate) or 1,1'-difluoro-2,2'-bipyridinium bis(tetrafluoroborate). [Item 11] The production method according to any one of Items 1 to 10, wherein the reaction is carried out in the presence of a solvent. [Item 12] R. １ and R ２ are independently a hydrogen atom, an alkyl group which may have one or more substituents, a cycloalkyl 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, a non-aromatic heterocyclic group which may have one or more substituents, a cyano group, a formyl group, R Ａ O-, R Ａ CO-, R Ａ SO ２ -, R Ａ COO-, (R Ａ ) (R Ｂ ) NCO-, R Ａ OCO-, R Ａ CONR Ｂ -, R Ａ OSO ２ -, or (R Ａ ) (R Ｂ ) NSO ２ - (wherein R Ａ and R Ｂ are independently an alkyl group which may have one or more substituents, an aryl group which may have one or more substituents, or an aralkyl group which may have one or more substituents; １ and R ２are combined with adjacent two carbon atoms to form a ring. [Item 13] A composition comprising: (B) at least one iodine source selected from iodine and ammonium iodide; and (C) a compound having at least one fluorinated quaternary nitrogen atom in the molecule (provided that when the iodine source (B) is iodine, the compound (C) is not an N-fluoropyridinium salt or a multimer thereof). [Item 14] The composition according to Item 13, further comprising: (A) at least one fluorine source selected from hydrogen fluoride, a hydrogen fluoride salt, and a fluoride salt. [Item 15] The composition according to Item 13 or 14, wherein the iodine source (B) is ammonium iodide. [Item 16] The composition according to any one of Items 13 to 15, wherein the amount of the iodine source (B) is 0.2 mol or less per mol of the compound (C). [Item 17] A fluorinating agent comprising the composition according to any one of Items 13 to 16.

[0006] According to the present disclosure, a novel method for producing a fluorinated organic compound is provided, which allows for easy removal or separation of auxiliary agents and is advantageous in terms of production costs.

[0007] The above summary of the present disclosure is not intended to describe each disclosed embodiment or every implementation of the present disclosure.

[0008] The remainder of this disclosure more particularly exemplifies example embodiments.

[0009] In several places in this disclosure, guidance is provided through examples, which examples can be used in various combinations.

[0010] In each instance, the exemplified group can serve as a non-exclusive and representative group.

[0011] All publications, patents, and patent applications cited herein are hereby incorporated by reference in their entirety.

[0012] 1. Terms and Conditions Unless otherwise specified, symbols and abbreviations used in this specification should be understood to have the meanings commonly used in the technical field to which this disclosure pertains, in accordance with the context of this specification.

[0013] As used herein, the phrase "comprising" is intended to encompass the phrases "consisting essentially of" and "consisting of."

[0014] Unless specifically limited, the steps, treatments, or operations described herein may be carried out at room temperature.

[0015] In this specification, room temperature can mean a temperature in the range of 10 to 40°C.

[0016] In this specification, the notation "C ｎ－ C ｍ (where n and m are each an integer of 1 or more, and n<m) represents that the number of carbon atoms is n or more and m or less, as would normally be understood by a person skilled in the art.

[0017] In this specification, the phrase "a compound represented by formula (N)" (wherein N is an integer of 1 or more) may be referred to as compound (N).

[0018] In this specification, unless otherwise specified, examples of the "halogen atom" include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.

[0019] In the present specification, the term "organic group" refers to a group containing one or more carbon atoms. Examples of the "organic group" include an alkyl group which may have one or more substituents, an alkenyl group which may have one or more substituents, an alkynyl group which may have one or more substituents, a cycloalkyl group which may have one or more substituents, a cycloalkenyl group which may have one or more substituents, a cycloalkadienyl 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, a non-aromatic heterocyclic group which may have one or more substituents, a heteroaryl group which may have one or more substituents, a cyano group, an aldehyde group, a carboxyl group, R ｒ O-, R ｒ CO-, R ｒ COO-, R ｒ SO ２ -, R ｒ OCO- and R ｒ OSO２ - (wherein R ｒ are independently an alkyl group which may have one or more substituents, an alkenyl group which may have one or more substituents, an alkynyl group which may have one or more substituents, a cycloalkyl group which may have one or more substituents, a cycloalkenyl group which may have one or more substituents, a cycloalkadienyl 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, a non-aromatic heterocyclic group which may have one or more substituents, or a heteroaryl group which may have one or more substituents.

[0020] In this specification, unless otherwise specified, examples of the "hydrocarbon group" include an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, a cycloalkenyl group, a cycloalkadienyl group, an aryl group, an aralkyl group, and groups that are combinations thereof.

[0021] Unless otherwise limited, examples of the "alkyl group" used herein include straight-chain or branched C1-16 alkyl groups (e.g., C1-C14 alkyl groups, C1-C12 alkyl groups) such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, nonyl, and decyl.

[0022] In this specification, unless otherwise limited, examples of the "alkenyl group" include linear or branched C2-C10 alkenyl groups such as vinyl, 1-propen-1-yl, 2-propen-1-yl, isopropenyl, 2-buten-1-yl, 4-penten-1-yl, and 5-hexen-1-yl.

[0023] Unless otherwise specified, examples of the "alkynyl group" used herein include straight-chain or branched-chain C2-C10 alkynyl groups such as ethynyl, 1-propyn-1-yl, 2-propyn-1-yl, 4-pentyn-1-yl, and 5-hexyn-1-yl.

[0024] In this specification, unless otherwise limited, examples of the "cycloalkyl group" include C3-C7 cycloalkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, etc.

[0025] In this specification, unless otherwise limited, examples of the "cycloalkenyl group" include C3-C7 cycloalkenyl groups such as cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, etc.

[0026] In this specification, unless otherwise limited, examples of the "cycloalkadienyl group" include C4-C10 cycloalkadienyl groups such as cyclobutadienyl, cyclopentadienyl, cyclohexadienyl, cycloheptadienyl, cyclooctadienyl, cyclononadienyl, and cyclodecadienyl.

[0027] In this specification, unless otherwise specified, the "aryl group" may be monocyclic, bicyclic, tricyclic, or tetracyclic.

[0028] In this specification, unless otherwise specified, the "aryl group" can be a C6-C18 aryl group.

[0029] In this specification, unless otherwise limited, examples of the "aryl group" include phenyl, 1-naphthyl, 2-naphthyl, 2-biphenyl, 3-biphenyl, 4-biphenyl, and 2-anthryl.

[0030] In this specification, unless otherwise limited, examples of the "aralkyl group" include benzyl, phenethyl, diphenylmethyl, 1-naphthylmethyl, 2-naphthylmethyl, 2,2-diphenylethyl, 3-phenylpropyl, 4-phenylbutyl, 5-phenylpentyl, 2-biphenylylmethyl, 3-biphenylylmethyl, and 4-biphenylylmethyl.

[0031] In this specification, unless otherwise specified, the "non-aromatic heterocyclic group" may be monocyclic, bicyclic, tricyclic, or tetracyclic.

[0032] In this specification, unless otherwise specified, the "non-aromatic heterocyclic group" may be, for example, a non-aromatic heterocyclic group containing, as ring-constituting atoms, in addition to carbon atoms, 1 to 4 heteroatoms selected from oxygen atoms, sulfur atoms, and nitrogen atoms.

[0033] In this specification, unless otherwise specified, the "non-aromatic heterocyclic group" may be saturated or unsaturated.

[0034] In this specification, unless otherwise limited, examples of the "non-aromatic heterocyclic group" include tetrahydrofuryl, oxazolidinyl, imidazolinyl (e.g., 1-imidazolinyl, 2-imidazolinyl, 4-imidazolinyl), aziridinyl (e.g., 1-aziridinyl, 2-aziridinyl), azetidinyl (e.g., 1-azetidinyl, 2-azetidinyl), pyrrolidinyl (e.g., 1-pyrrolidinyl), and the like. nyl, 2-pyrrolidinyl, 3-pyrrolidinyl), piperidinyl (e.g., 1-piperidinyl, 2-piperidinyl, 3-piperidinyl), azepanyl (e.g., 1-azepanyl, 2-azepanyl, 3-azepanyl, 4-azepanyl), azocanyl (e.g., 1-azocanyl, 2-azocanyl, 3-azocanyl, 4-azocanyl), piperazinyl (e.g., 1,4-piperazine-1 -yl, 1,4-piperazin-2-yl), diazepinyl (e.g., 1,4-diazepin-1-yl, 1,4-diazepin-2-yl, 1,4-diazepin-5-yl, 1,4-diazepin-6-yl), diazocanyl (e.g., 1,4-diazocan-1-yl, 1,4-diazocan-2-yl, 1,4-diazocan-5-yl, 1,4-diazocan-6-yl, 1,5-diazocan-1-yl, 1,5-diazocan-2-yl, 1,5-diazocan-3-yl), tetrahydropyranyl (e.g., tetrahydropyran-4-yl), morpholinyl (e.g., 4-morpholinyl), thiomorpholinyl (e.g., 4-thiomorpholinyl), 2-oxazolidinyl, dihydrofuryl, dihydropyranyl, and dihydroquinolyl.

[0035] Unless otherwise specified, examples of the "heteroaryl group" used herein include monocyclic aromatic heterocyclic groups (e.g., 5- or 6-membered monocyclic aromatic heterocyclic groups) and aromatic fused heterocyclic groups (e.g., 5- to 18-membered aromatic fused heterocyclic groups).

[0036] In this specification, unless otherwise limited, examples of the "5- or 6-membered monocyclic aromatic heterocyclic group" include pyrrolyl (e.g., 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl), furyl (e.g., 2-furyl, 3-furyl), thienyl (e.g., 2-thienyl, 3-thienyl), pyrazolyl (e.g., 1-pyrazolyl, 3-pyrazolyl, 4-pyrazolyl), imidazolyl (e.g., 1-imidazolyl, 2-imidazolyl, 4-imidazolyl), isoxazolyl (e.g., 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl), oxazolyl (e.g., 2-oxazolyl, 4-oxazolyl, 5-oxazolyl), isothiazolyl (e.g., 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl), aryl), thiazolyl (e.g., 2-thiazolyl, 4-thiazolyl, 5-thiazolyl), triazolyl (e.g., 1,2,3-triazol-4-yl, 1,2,4-triazol-3-yl), oxadiazolyl (e.g., 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl), thiadiazolyl (e.g., 1,2,4-thiadiazol-3-yl, 1,2,4-thiadiazol-5-yl), tetrazolyl, pyridyl (e.g., 2-pyridyl, 3-pyridyl, 4-pyridyl), pyridazinyl (e.g., 3-pyridazinyl, 4-pyridazinyl), pyrimidinyl (e.g., 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl), pyrazinyl, and the like.

[0037] In this specification, unless otherwise limited, examples of the "5- to 18-membered aromatic fused heterocyclic group" include isoindolyl (e.g., 1-isoindolyl, 2-isoindolyl, 3-isoindolyl, 4-isoindolyl, 5-isoindolyl, 6-isoindolyl, 7-isoindolyl), indolyl (e.g., 1-indolyl, 2-indolyl, 3-indolyl, 4-indolyl, 5-indolyl, 6-indolyl, 7-indolyl), benzo[b]furanyl (e.g., 2-benzo[b]furanyl, 3-benzo[b]furanyl, 4-benzo[b]furanyl, benzo[b]furanyl, 5-benzo[b]furanyl, 6-benzo[b]furanyl, 7-benzo[b]furanyl), benzo[c]furanyl (e.g., 1-benzo[c]furanyl, 4-benzo[c]furanyl, 5-benzo[c]furanyl), benzo[b]thienyl, (e.g., 2-benzo[b]thienyl, 3-benzo[b]thienyl, 4-benzo[b]thienyl, 5-benzo[b]thienyl, 6-benzo[b]thienyl, 7-benzo[b]thienyl), benzo[c]thienyl (e.g., 1-benzo[c]thienyl, 4-benzo [c]thienyl, 5-benzo[c]thienyl), indazolyl (e.g., 1-indazolyl, 2-indazolyl, 3-indazolyl, 4-indazolyl, 5-indazolyl, 6-indazolyl, 7-indazolyl), benzimidazolyl (e.g., 1-benzimidazolyl, 2-benzimidazolyl, 4-benzimidazolyl, 5-benzimidazolyl), 1,2-benzisoxazolyl (e.g., 1,2-benzisoxazol-3-yl, 1,2-benzisoxazol-4-yl, 1,2-benzisooxazol-5-yl, 1,2-benzisooxazol-6-yl, 1,2-benzisooxazol-7-yl, 1,2-benzisooxazol-8-yl, 1,2-benzisooxazol-9-yl, 1,2-benzisooxazol-10-yl, 1,2-benzisooxazol-11-yl, 1,2-benzisooxazol-12-yl, 1,2-benzisooxazol-13-yl, 1,2-benzisooxazol-14-yl, 1,2-benzisooxazol-15-yl, 1,2-benzisooxazol-16-yl, 1,2-benzisooxazol-17-yl, 1,2-benzisooxazol-18-yl, 1,2-benzisooxazol-19-yl, 1,2-benzisooxazol-20-yl, 1,2-benzisooxazol-21-yl, 1,2-benzisooxazol-22-yl, 1,2-benzisooxazol benzoxazolyl (e.g., 2-benzoxazolyl, 4-benzoxazolyl, 5-benzoxazolyl, 6-benzoxazolyl, 7-benzoxazolyl), 1,2-benzisothiazolyl (e.g., 1,2-benzisothiazol-3-yl, 1,2-benzisothiazol-4-yl, 1,2-benzisothiazol-5-yl, 1,2-benzisothiazol-6-yl, 1,2-benzisoxazol-7-yl), benzoxazolyl (e.g., 2-benzoxazolyl, 4-benzoxazolyl, 5-benzoxazolyl, 6-benzoxazolyl, 7-benzoxazolyl), 1,2-benzisothiazolyl (e.g., 1,2-benzisothiazol-3-yl, 1,2-benzisothiazol-4-yl, 1,2-benzisothiazol-5-yl, 1,2-benzisothiazol-6-yl, 1,2-benzisothiazol-7-yl), benzothiazolyl (e.g., 2-benzothiazolyl, 4-benzothiazolyl, 5-benzothiazolyl, 6-benzothiazolyl, 7-benzothiazolyl), isoquinolyl (e.g., 1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl, 5-isoquinolyl), quinolyl (e.g., 2-quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl, 8-quinolyl), cinnolinyl (e.g., : 3-cinnolinyl, 4-cinnolinyl, 5-cinnolinyl, 6-cinnolinyl, 7-cinnolinyl, 8-cinnolinyl), phthalazinyl (e.g., 1-phthalazinyl, 4-phthalazinyl, 5-phthalazinyl, 6-phthalazinyl, 7-phthalazinyl, 8-phthalazinyl), quinazolinyl (e.g., 2-quinazolinyl, 4-quinazolinyl, 5-quinazolinyl, 6-quinazolinyl, 7-quinazolinyl, 8-quinazolinyl), quinoxalinyl (e.g., 2-quinoxalinyl, 3-quinoxalinyl, 5-quinoxalinyl, 6-quinoxalinyl, 7-quinoxalinyl, 8-quinoxalinyl), pyrazolo[1,5-a]pyridyl (e.g., pyrazolo[1,5-a]pyridin-2-yl, pyrazolo[1,5-a]pyridin-3-yl, pyrazolo[1,5-a]pyridin-4-yl, pyrazolo[1,5-a]pyridin-5-yl, pyrazolo[1,5-a] pyridin-6-yl, pyrazolo[1,5-a]pyridin-7-yl), imidazo[1,2-a]pyridyl (e.g., imidazo[1,2-a]pyridin-2-yl, imidazo[1,2-a]pyridin-3-yl, imidazo[1,2-a]pyridin-5-yl, imidazo[1,2-a]pyridin-6-yl, imidazo[1,2-a]pyridin-7-yl, imidazo[1,2-a]pyridin-8-yl), and the like.

[0038] In this specification, "R ｒ Examples of "O-" include alkoxy (e.g., C1-C10 alkoxy such as methoxy, ethoxy, propoxy, butoxy, etc.), cycloalkoxy (e.g., C3-C7 cycloalkoxy such as cyclopentoxy, cyclohexoxy, etc.), aryloxy (e.g., C6-C18 aryloxy such as phenoxy, naphthoxy, etc.), and aralkyloxy (e.g., C7-C19 aralkyloxy such as benzyloxy, phenethyloxy, etc.).

[0039] In this specification, "R ｒ Examples of "CO-" include alkylcarbonyl [e.g., (C1-C10 alkyl)carbonyl such as acetyl, propionyl, butyryl, etc.], cycloalkylcarbonyl [e.g., (C3-C7 cycloalkyl)carbonyl such as cyclopentanoyl, cyclohexanoyl, etc.], arylcarbonyl [e.g., (C6-C18 aryl)carbonyl such as benzoyl, naphthoyl, etc.], and aralkylcarbonyl [e.g., (C7-C19 aralkyl)carbonyl such as benzylcarbonyl, phenethylcarbonyl, etc.].

[0040] In this specification, "R ｒ Examples of "COO-" include alkylcarbonyloxy [e.g., (C1-C10 alkyl)carbonyloxy such as acetyloxy, propionyloxy, butyryloxy, etc.], cycloalkylcarbonyloxy [e.g., (C3-C7 cycloalkyl)carbonyloxy such as cyclopentanoyl, cyclohexanoyloxy, etc.], arylcarbonyloxy [e.g., (C6-C18 aryl)carbonyloxy such as benzoyloxy, naphthoyloxy, etc.], and aralkylcarbonyloxy [e.g., (C7-C19 aralkyl)carbonyloxy such as benzylcarbonyloxy, phenethylcarbonyloxy, etc.].

[0041] In this specification, "R ｒ SO ２ Examples of "-" include alkylsulfonyl (e.g., C1-C10 alkylsulfonyl such as methylsulfonyl, ethylsulfonyl, propylsulfonyl, etc.), cycloalkylsulfonyl (e.g., C4-C8 cycloalkylsulfonyl such as cyclopentylsulfonyl, cyclohexylsulfonyl, etc.), arylsulfonyl (e.g., C6-C18 arylsulfonyl such as phenylsulfonyl, naphthylsulfonyl, etc.), and aralkylsulfonyl (e.g., C7-C19 aralkylsulfonyl such as benzylsulfonyl, phenethylsulfonyl, etc.).

[0042] In this specification, "R ｒExamples of "OCO-" include alkoxycarbonyl [e.g., (C1-C10 alkoxy)carbonyl such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, etc.], cycloalkoxycarbonyl [e.g., (C3-C7 cycloalkoxy)carbonyl such as cyclopentoxycarbonyl, cyclohexoxycarbonyl, etc.], aryloxycarbonyl [e.g., (C6-C18 aryloxy)carbonyl such as phenoxycarbonyl, naphthoxycarbonyl, etc.], and aralkyloxycarbonyl [e.g., (C7-C19 aralkyloxy)carbonyl such as benzyloxycarbonyl, phenethyloxycarbonyl, etc.].

[0043] In this specification, "R ｒ OSO ２ Examples of "-" include alkoxysulfonyl (e.g., C1-C10 alkoxysulfonyl such as methoxysulfonyl, ethoxysulfonyl, propoxysulfonyl, etc.), cycloalkoxysulfonyl (e.g., C3-C7 cycloalkoxysulfonyl such as cyclopentoxysulfonyl, cyclohexoxysulfonyl, etc.), aryloxysulfonyl (e.g., C6-C18 aryloxysulfonyl such as phenoxysulfonyl, naphthoxysulfonyl, etc.), and aralkyloxysulfonyl (e.g., C7-C19 aralkyloxysulfonyl such as benzyloxysulfonyl, phenethyloxysulfonyl, etc.).

[0044] In this specification, examples of the "substituent" in the "hydrocarbon group which may have one or more substituents", "alkyl group which may have one or more substituents", "alkenyl group which may have one or more substituents", "alkynyl group which may have one or more substituents", "cycloalkyl group which may have one or more substituents", "cycloalkenyl group which may have one or more substituents", "cycloalkadienyl group which may have one or more substituents", "aryl group which may have one or more substituents", "aralkyl group which may have one or more substituents", "non-aromatic heterocyclic group which may have one or more substituents", and "heteroaryl group which may have one or more substituents" respectively include a halo group, a nitro group, a cyano group, an oxo group, a thioxo group, a carboxyl group, an amino group, a quaternary ammonium group, a sulfo group, a sulfamoyl group, a sulfinamoyl group, a sulfenamoyl group, an R ｒ O-, R ｒ CO-, R ｒ COO-, R ｒ SO ２ -, R ｒ OCO- and R ｒ OSO ２ - (wherein R ｒ has the same meaning as above.

[0045] Among the substituents, examples of the "halo group" include a fluoro group, a chloro group, a bromo group, and an iodo group.

[0046] The number of such substituents can be within the range of 1 to the maximum number of possible substitutions (e.g., 1, 2, 3, 4, 5, 6).

[0047] In this specification, the term "electron-withdrawing group" refers to a group whose σp value according to Hammett's rule is positive.

[0048] 2. Method for Producing Difluorinated Compound (1) The method for producing a difluorinated compound (1) includes step A of reacting compound (1) with a fluorine source (A), an iodine source (B), and compound (C) to difluorinate compound (1).

[0049] 2-1. Compound (1) In one embodiment of compound (1), R １ and R ２ are independently a hydrogen atom, an alkyl group which may have one or more substituents, a cycloalkyl 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, a non-aromatic heterocyclic group which may have one or more substituents, a cyano group, a formyl group, R Ａ O-, R Ａ CO-, R Ａ SO ２ -, R Ａ COO-, (R Ａ )(R Ｂ )NCO-, R Ａ OCO-, R Ａ CONR Ｂ -, R Ａ OSO ２ - or (R Ａ )(R Ｂ ) NSO ２ - (wherein R Ａ and R Ｂ are each independently an alkyl group which may have one or more substituents, an aryl group which may have one or more substituents, or an aralkyl group which may have one or more substituents.

[0050] The substituent may be any group having a structure that can be substituted, for example, at least one selected from the group consisting of a halo group, a hydroxy group, an alkoxy group, an alkylcarbonyl group, an alkylcarbonyloxy group, an alkoxycarbonyl group, an arylcarbonyloxy group, an aryloxycarbonyl group, and an aryl group. The number of the substituents may be selected from the range of 1 to the maximum number that can be substituted (e.g., 1, 2, 3).

[0051] In the above embodiment, R １ and R ２ At least one of the groups is a cyano group, a formyl group, or R Ａ CO-, R Ａ SO ２ -, R Ａ OCO-, RＡ OSO ２ The reaction also proceeds with respect to the compound (1) having such an electron-deficient double bond or triple bond.

[0052] In another embodiment of compound (1), R １ and R ２ preferably forms a ring together with the two adjacent carbon atoms. A ring is usually formed when the symbol is a double bond and n is 2. Examples of such rings include cycloalkene rings corresponding to the groups exemplified as "cycloalkenyl groups," and non-aromatic heterocyclic rings corresponding to the groups having a carbon-carbon double bond among the groups exemplified as "non-aromatic heterocyclic groups."

[0053] The ring may have one or more substituents. Examples of the substituents include a hydrocarbon group, a halo group, a nitro group, a cyano group, an oxo group, a thioxo group, a carboxyl group, a sulfo group, a sulfamoyl group, a sulfinamoyl group, a sulfenamoyl group, R ｒ O-, R ｒ CO-, R ｒ COO-, R ｒ SO ２ -, R ｒ OCO- and R ｒ OSO ２ - (wherein R ｒ has the same meaning as defined above. The number of the substituents can be selected from the range of 1 to the maximum number of substituents possible (e.g., 1, 2, 3, 4, 5).

[0054] A suitable example of compound (1) is a compound represented by the following formula (1A): (In the formula, R １１ , R １２ , R ２１ , and R ２２ are independently a hydrogen atom or an organic group, or R １１ and R １２ , or R ２１ and R ２２ R is taken together with one adjacent carbon atom to form a ring, or R １１ and R ２１ , R １１ and R２２ , R １２ and R ２１ , or R １２ and R ２２ forms a ring together with two adjacent carbon atoms, and the symbol: indicates a cis or trans configuration, and a compound represented by the following formula (1B): (In the formula, R １３ and R ２３ are independently a hydrogen atom or an organic group.

[0055] In one embodiment of compound (1A), R １１ , R １２ , R ２１ , and R ２２ are independently a hydrogen atom, an alkyl group which may have one or more substituents, a cycloalkyl 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, a non-aromatic heterocyclic group which may have one or more substituents, a cyano group, a formyl group, R Ａ O-, R Ａ CO-, R Ａ SO ２ -, R Ａ COO-, (R Ａ )(R Ｂ )NCO-, R Ａ OCO-, R Ａ CONR Ｂ -, R Ａ OSO ２ - or (R Ａ )(R Ｂ ) NSO ２ - (wherein R Ａ and R Ｂ are each independently an alkyl group which may have one or more substituents, an aryl group which may have one or more substituents, or an aralkyl group which may have one or more substituents.

[0056] In the above embodiment, R ２２ is preferably a hydrogen atom, and R １２ and R ２２It is more preferable that R is a hydrogen atom. １２ , R ２１ , and R ２２ It is also preferred that is a hydrogen atom.

[0057] In the above embodiment, R １２ and R ２２ is a hydrogen atom, and R １１ and R ２１ It is also preferable that R is other than a hydrogen atom. The reaction proceeds successfully even with the compound (1) having such a double bond inside. １１ and R ２１ At least one of the groups is a cyano group, a formyl group, or R Ａ CO-, R Ａ SO ２ -, R Ａ OCO-, R Ａ OSO ２ The reaction also proceeds with respect to the compound (1) having such an electron-deficient double bond.

[0058] Suitable examples of compound (1A) include compounds represented by the following formulae (1a) to (1d): (In the formula, R １ａ represents an alkyl group which may have one or more substituents, an aryl group which may have one or more substituents, or an aralkyl group which may have one or more substituents, and R １ｂ and R ２ｂ are independently an alkyl group which may have one or more substituents, an aryl group which may have one or more substituents, or an aralkyl group which may have one or more substituents, １ｃ is a hydrogen atom, an alkyl group which may have one or more substituents, an aryl group which may have one or more substituents, or an aralkyl group which may have one or more substituents, ２ｃ is an alkyl group which may have one or more substituents, and R １ｄ is a hydrogen atom, an alkyl group which may have one or more substituents, an aryl group which may have one or more substituents, or an aralkyl group which may have one or more substituents, ２ｄis an alkyl group which may have one or more substituents, an aryl group which may have one or more substituents, or an aralkyl group which may have one or more substituents. The substituent may be any group having a structure which can be substituted with the target, and may be, for example, at least one selected from the group consisting of a halo group, a hydroxyl group, an alkoxy group, an alkylcarbonyl group, an alkylcarbonyloxy group, an alkoxycarbonyl group, an arylcarbonyloxy group, an aryloxycarbonyl group, and an aryl group. The number of the substituents may be selected from the range of 1 to the maximum number of substituents (e.g., 1, 2, or 3).

[0059] In one embodiment of compound (1a), R １ａ is an alkyl group optionally having one or more substituents (e.g., a halo group, a hydroxy group, an alkoxycarbonyl group), or an aralkyl group optionally having one or more substituents (e.g., a halo group, a hydroxy group, an alkoxycarbonyl group). １ｃ is an aryl group optionally having one or more substituents (e.g., halo group). In one embodiment of compound (1d), R １ｄ is an aryl group which may have one or more substituents (e.g., halo groups), and R ２ｄ is an alkyl group which may have one or more substituents (e.g., halo groups), or an aryl group which may have one or more substituents (e.g., halo groups).

[0060] In one embodiment of compound (1B), R １３ and R ２３ are independently a hydrogen atom, an alkyl group which may have one or more substituents, a cycloalkyl 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, a non-aromatic heterocyclic group which may have one or more substituents, a cyano group, a formyl group, R Ａ O-, R Ａ CO-, R Ａ SO ２ -, R Ａ COO-, (RＡ )(R Ｂ )NCO-, R Ａ OCO-, R Ａ CONR Ｂ -, R Ａ OSO ２ - or (R Ａ )(R Ｂ ) NSO ２ - (wherein R Ａ and R Ｂ are each independently an alkyl group which may have one or more substituents, an aryl group which may have one or more substituents, or an aralkyl group which may have one or more substituents.

[0061] In the above embodiment, R １３ and R ２３ It is also preferable that R is other than a hydrogen atom. The reaction proceeds successfully even with the compound (1) having such a triple bond inside. １３ and R ２３ At least one of the groups is a cyano group, a formyl group, or R Ａ CO-, R Ａ SO ２ -, R Ａ OCO-, R Ａ OSO ２ The reaction also proceeds with respect to the compound (1) having such an electron-deficient triple bond.

[0062] 2-2. Fluorine Source (A) In the method for producing a difluoride of compound (1), the fluorine source (A) is at least one selected from hydrogen fluoride, a hydrogen fluoride salt, and a fluoride salt.

[0063] Of the fluorine sources (A), hydrogen fluoride can be used in the form of an aqueous solution (hydrofluoric acid). The aqueous solution can be, for example, an aqueous solution having a hydrogen fluoride concentration of 10 to 70 mass %.

[0064] Among the fluorine sources (A), examples of hydrogen fluoride salts include amine hydrogen fluoride salts and ammonium hydrogen fluoride salts.

[0065] In the amine hydrogen fluoride salt, the amine can be a chain amine or a cyclic amine.

[0066] Examples of linear amines include aliphatic primary amines, aliphatic secondary amines, and aliphatic tertiary amines. Examples of aliphatic primary amines include C1-C6 alkylamines such as methylamine, ethylamine, propylamine, butylamine, pentylamine, and hexylamine. Examples of aliphatic secondary amines include di-C1-C6 alkylamines such as dimethylamine, diethylamine, dipropylamine, dibutylamine, dipentylamine, and dihexylamine. Examples of aliphatic tertiary amines include tri-C1-C6 alkylamines such as trimethylamine, triethylamine, diisopropylethylamine, tributylamine, and N,N,N',N'-tetramethylethylenediamine.

[0067] Examples of cyclic amines include aliphatic cyclic amines and aromatic cyclic amines. Examples of aliphatic cyclic amines include piperidine, piperazine, pyrrolidine, morpholine, N-methylpiperazine, N-methylpyrrolidine, 5-diazabicyclo[4.3.0]nonan-5-ene, and 1,4-diazabicyclo[2.2.2]octane. Examples of aromatic cyclic amines include pyridine, pyrimidine, pyrazine, quinoline, and imidazole.

[0068] A suitable example of the hydrogen fluoride amine salt is hydrogen fluoride triethylamine salt (Et ３ N.xHF (x is an integer of 1 or more, preferably 1 to 10, and more preferably 3 to 7)), pyridine hydrogen fluoride salts such as Olah's reagent (Py.xHF (x is an integer of 1 or more, preferably 1 to 10)), and combinations thereof.

[0069] Examples of ammonium hydrogen fluoride salts include those represented by the following formula (A1): NQ ４ F.xHF (A1) (wherein each Q is independently a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, or an aralkyl group, or two or three Qs are bonded to each other to form a ring, and x is an integer of 1 or greater).

[0070] In one embodiment of compound (A1), Q is preferably an alkyl group, more preferably a C1-C6 alkyl group. x is preferably 1 to 10.

[0071] A suitable example of the compound (A1) is ammonium hydrogen fluoride (NH ４ F·HF), hydrogen fluoride-tetramethylammonium fluoride, hydrogen fluoride-tetraethylammonium fluoride, hydrogen fluoride-tetrapropylammonium fluoride, and hydrogen fluoride-tetrabutylammonium fluoride.

[0072] Among the fluorine sources (A), examples of fluoride salts include those represented by the following formula (A2): １ F ｍ１ (A2) (wherein, M １ is an alkali metal or alkaline earth metal; and m1 is M １ The valence of the aryl group is 1 or 2, depending on the valence of the aryl group.

[0073] In one embodiment of compound (A2), preferably M １ is Li, Na, K, Ca, or Cs, and more preferably M １ is Na, K, or Ca, and more preferably M １ is K.

[0074] The fluoride salt is preferably an alkali metal fluoride salt (M １ is an alkali metal and m1 is 1) or an alkaline earth metal fluoride salt (M １ is an alkaline earth metal and m1 is 2).

[0075] The fluorine source (A) may be used alone or in combination of two or more. In a preferred embodiment, the fluorine source (A) is at least one selected from hydrogen fluoride, hydrogen fluoride amine salts, alkali metal fluoride salts, and alkaline earth metal fluoride salts.

[0076] The amount of the fluorine source (A) used is not particularly limited. The lower limit of the amount of the fluorine source (A) used can be, for example, 0.1 mol or more, preferably 0.2 mol or more, more preferably 0.3 mol or more, even more preferably 0.4 mol or more, and particularly preferably 0.5 mol or more, relative to 1 mol of compound (1). The upper limit of the amount of the fluorine source (A) used can be, for example, 1000 mol or less, preferably 500 mol or less, more preferably 300 mol or less, even more preferably 100 mol or less, even more preferably 90 mol or less, and particularly preferably 80 mol or less, relative to 1 mol of compound (1). The amount of the fluorine source (A) used can be, for example, in the range of 0.1 to 1000 mol, preferably in the range of 0.2 to 500 mol, more preferably in the range of 0.3 to 100 mol, even more preferably in the range of 0.4 to 90 mol, and particularly preferably in the range of 0.5 to 80 mol.

[0077] The fluorine source (A) remaining after the reaction may be trapped and discarded, but is preferably recovered and reused from the viewpoint of production costs. The trapped fluorine source (A) remaining after the reaction may be washed with, for example, water or alkaline water.

[0078] 2-3. Iodine Source (B) In the method for producing a difluoride of compound (1), the iodine source (B) is at least one selected from iodine and ammonium iodide. A difluorination reaction using an iodine source in an amount less than the equivalent has not been reported to date. By reducing the amount of the iodine source used, separation or removal becomes easier, thereby reducing production costs.

[0079] Among the iodine sources (B), iodine is molecular iodine (I ２ ) means

[0080] Among the iodine sources (B), ammonium iodide is, for example, a compound represented by the formula: N(R Ｂ ) ４ I (where four R Ｂ are independently a hydrogen atom or an alkyl group which may have one or more substituents.

[0081] R ＢSuitable examples include C1-C12 alkanes which may have one or more substituents. Examples of the substituents include a halogen atom (e.g., an iodine atom). The number of the substituents can be selected from the range of 1 to the maximum number of substituents (e.g., 1, 2, or 3).

[0082] An example of an ammonium iodide is ammonium iodide (NH ４ I), tetramethylammonium iodide (TMAI), tetraethylammonium iodide (TEAI), tetrapropylammonium iodide, tetrabutylammonium iodide (TBAI), tetrapentylammonium iodide, tetrahexylammonium iodide, tetraheptylammonium iodide, tetraoctylammonium iodide, ethyltripropylammonium iodide, 5-azoniaspiro[4,4]nonane iodide, benzyltriethylammonium iodide, dimethyldioctadecylammonium iodide, ethyltrimethylammonium iodide, (2-hydroxyethyl)triethylammonium iodide, triethylphenylammonium iodide, trimethylphenylammonium iodide, tributylmethylammonium iodide, choline iodide, butylthiocholine iodide, β-methylcholine iodide, acetylcholine iodide, acetylthiocholine iodide, benzoylcholine iodide, benzoylthiocholine iodide, isopropamide iodide, and decamethonium iodide.

[0083] The iodine source (B) may be used alone or in combination of two or more.

[0084] The amount of the iodine source (B) used is not particularly limited as long as it is less than 1.0 mol per mole of compound (1). The lower limit of the amount of the iodine source (B) used can be, for example, 0.001 mol or more, preferably 0.005 mol or more, more preferably 0.01 mol or more, even more preferably 0.05 mol or more, and particularly preferably 0.1 mol or more per mole of compound (1). The upper limit of the amount of the iodine source (B) used can be, for example, 0.9 mol or less, more preferably 0.7 mol or less, even more preferably 0.5 mol or less, even more preferably 0.4 mol or less, and particularly preferably 0.2 mol or less per mole of compound (1). The amount of the iodine source (B) used can be, for example, in the range of 0.001 mol or more and less than 1.0 mol, preferably 0.005 to 0.9 mol, more preferably 0.01 to 0.7 mol, even more preferably 0.05 to 0.4 mol, and even more preferably 0.1 to 0.2 mol per mole of compound (1). Even when such a small amount of the iodine source (B) is used, the reaction proceeds in a good yield.

[0085] The iodine source (B) remaining after the reaction may be trapped and discarded, but is preferably recovered and reused from the viewpoint of production costs. The trapped iodine source (B) remaining after the reaction may be washed with, for example, water or alkaline water. Unlike conventional organic iodine compounds, the iodine source (B) can be easily removed by washing with water. By using such an iodine source (B) in a relatively small amount, the target difluoride can be easily purified, thereby further reducing the production cost of the difluoride.

[0086] 2-4. Compound (C) In the method for producing the difluorinated compound of compound (1), compound (C) is a compound having at least one fluorinated quaternary nitrogen atom in the molecule.

[0087] In one embodiment, compound (C) is a salt comprising a cation having at least one fluorinated quaternary nitrogen atom and a counter anion.

[0088] In the above embodiment, the compound (C) is, for example, a compound represented by the general formula (2): (R Ｃ )３ N ＋ -F (2) (wherein three R Ｃ are independently an organic group, or three R Ｃ may each be bonded to the adjacent nitrogen atom to form a ring (hereinafter, sometimes simply referred to as "cation (2)").

[0089] In general formula (2), R Ｃ Suitable examples include C1-C12 alkanes which may have one or more substituents. Examples of the substituents include a halogen atom (e.g., an iodine atom). The number of the substituents can be selected from the range of 1 to the maximum number of substituents (e.g., 1, 2, or 3).

[0090] In general formula (2), three R Ｃ preferably form a ring together with the adjacent nitrogen atom. Examples of such rings include non-aromatic heterocycles corresponding to the groups having a tertiary nitrogen atom among the groups exemplified as "non-aromatic heterocyclic groups", and aromatic heterocycles corresponding to the groups having a tertiary nitrogen atom among the groups exemplified as "heteroaryl groups". Examples of such rings include bicyclo rings such as azabicyclo rings and diazabicyclo rings. That is, specific examples of such rings include 5-diazabicyclo[4.3.0]nonan-5-ene and 1,4-diazabicyclo[2.2.2]octane.

[0091] The ring may have one or more substituents. Examples of the substituents include a halogen atom, a hydroxy group, an alkyl group (e.g., a C1-C15 alkyl group) optionally having one or more further substituents (e.g., a halogen atom), an alkenyl group (e.g., a C1-C15 alkenyl group) optionally having one or more further substituents (e.g., a halogen atom), an alkynyl group (e.g., a C1-C15 alkynyl group) optionally having one or more further substituents (e.g., a halogen atom), an aryl group (e.g., a C6-C15 aryl group) optionally having one or more further substituents (e.g., a halogen atom, an alkyl group), a nitro group, a cyano group, R Ｆ O-, R Ｆ CO-, R Ｆ SO２ -, R Ｆ COO-, (R Ｆ )(R Ｇ )NCO-, R Ｆ OCO-, R Ｆ CONR Ｇ -, R Ｆ OSO ２ -, and (R Ｆ )(R Ｇ ) NSO ２ - (wherein R Ｆ and R Ｇ are independently an alkyl group which may have one or more substituents (e.g., a halogen atom), or an aryl group which may have one or more substituents (e.g., a halogen atom, an alkyl group). The number of the substituents can be selected from within the range of 1 to the maximum number of substituents possible (e.g., 1, 2, 3, 4, or 5).

[0092] The compound (C) preferably contains a conjugate base of a Bronsted acid as a counter anion of the cation (2). Examples of Bronsted acids include inorganic acids and organic acids. Examples of inorganic acids include hydrofluoric acid, hydrochloric acid, perchloric acid, sulfuric acid, persulfuric acid, fluorosulfuric acid, chlorosulfuric acid, phosphoric acid, boric acid, nitric acid, and HBF. ４ , H.B. ２ F ７ , HBCl ４ , HBCl ３ F, HBBr ３ F, HPF ６ , HAsF ６ , HSbF ４ , HSbF ６ , HSbCl ６ , HSbCl ５ F, HSb ２ F １１ , HAlF ４ , HAlCl ４ , HAlCl ３ F, and HAlF ３Examples of the organic acid include carboxylic acids such as acetic acid, trifluoroacetic acid, trichloroacetic acid, and pentafluoropropionic acid, sulfonic acids such as methanesulfonic acid, trifluoromethanesulfonic acid, trichloromethanesulfonic acid, ethanesulfonic acid, perfluoroethanesulfonic acid, propanesulfonic acid, perfluoropropanesulfonic acid, butanesulfonic acid, perfluorobutanesulfonic acid, benzenesulfonic acid, toluenesulfonic acid, and nitrobenzenesulfonic acid, alkyl sulfuric acids such as methyl sulfuric acid, and sulfonylimide acids such as bis(methanesulfonyl)imide acid and bis(trifluoromethanesulfonyl)imide acid.

[0093] Examples of conjugate bases of the Bronsted acids include: － OClO ３ , － OSO ２ OH, － OSO ２ F. － OSO ２ Cl, － BF ４ , － B ２ F ７ , － PF ６ , － AsF ６ , － SbF ６ , － AlF ４ , － AlCl ４ , － SbCl ６ , － SbCl ５ F. － Sb ２ F １１ , － OSO ２ CH ３ , － OSO ２ CF ３ , － OSO ２ CCl ３ , － OSO ２ C ４ F ９ , － OSO２ C ６ H ５ , － OSO ２ C ６ H ４ CH ３ , － OSO ２ C ６ H ４ NO ２ , － OSO ２ OCH ３ , － N(SO ２ CH ３ ) ２ , and － N(SO ２ CF ３ ) ２ Includes.

[0094] Examples of compound (C) include 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2,2,2]octane bis(tetrafluoroborate) (Selectfluor), 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2,2,2]octane fluoride(tetrafluoroborate), 1-fluoro-4-hydroxy-1,4-diazoniabicyclo[2,2,2]octane bis(tetrafluoroborate), 1-fluoro-4-methyl-1,4-diazoniabicyclo[2,2,2]octane bis(tetrafluoroborate), and N-fluoro-quinuclidinium triflate.

[0095] In the above embodiment, compound (C) may be an N-fluoropyridinium salt or a multimer thereof. As will be apparent to those skilled in the art, the above cation (2) encompasses N-fluoropyridinium cations and multimers thereof. In this case, three R Ｃ are each taken together with the adjacent nitrogen atom to form a pyridine ring.

[0096] Examples of N-fluoropyridinium salts include compounds represented by the following formula (2-1), which may have one or more substituents: (wherein X represents a conjugate base of a Bronsted acid).

[0097] An example of the N-fluoropyridinium salt multimer is a multimer of compound (2-1) which may have one or more substituents. One example of the multimer is a multimer of the following formula (2-2): (wherein X has the same meaning as defined above).

[0098] The compound (2-2) which may have one or more substituents is represented by the following formulae (2-3) to (2-7), which may have one or more substituents: (wherein X has the same meaning as defined above) Among these, compound (2-3) which may have one or more substituents is preferred, and compound (2-3) (which has no substituents) is more preferred.

[0099] Another example of the N-fluoropyridinium salt multimer is a compound represented by the following formula (2-8): (wherein X is as defined above, L is a single bond, —CH ２ - or -O-, and z is an integer of 2 or more.

[0100] The content of the polymerized units (2-8) in the polymer is preferably 50 mol % or more, and more preferably 60 mol % or more.

[0101] The polymer may contain copolymerized units in addition to the polymerized units (2-8). Examples of the copolymerized units include arylenes which may have one or more substituents (e.g., C6-C12 arylenes such as phenylene and naphthalenediyl), and heteroarylenes which may have one or more substituents (e.g., thiophenediyl, furandiyl, pyrrolediyl, pyridinediyl). Examples of the substituents which may be substituted on these copolymerized units include the same as the examples of the substituents which may be substituted on the polymerized units (2-8).

[0102] Although z is not particularly limited as long as it is an integer of 2 or more, it is preferably 2, 3, or 4. The average molecular weight of the polymer is preferably within the range of 100 to 500,000.

[0103] Examples of the conjugate base of the Bronsted acid represented by X, which constitutes the compounds (2-1) to (2-7) and the polymer (2-8), include the same as the "conjugate base of the Bronsted acid" exemplified as the counter anion of the cation (2). One type of conjugate base can be used alone, or two or more types can be used in combination.

[0104] Examples of the substituents that can be substituted on the compounds (2-1) to (2-7) and the polymer (2-8) include the three R ｃ The number of the substituents can be selected from the range of 1 to the maximum number of substituents (e.g., 1, 2, 3, 4, 5, 6, 7, 8).

[0105] Examples of N-fluoropyridinium salts and multimers thereof include 1-fluoro-pyridinium pyridine heptafluorodiborate, 1-fluoro-pyridinium tetrafluoroborate, 1-fluoro-pyridinium triflate, 1-fluoro-2,6-dichloropyridinium tetrafluoroborate, and 1,1′-difluoro-2,2′-bipyridinium bis(tetrafluoroborate) (Synfluor).

[0106] In the above embodiment, compound (C) is preferably at least one selected from 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2,2,2]octane bis(tetrafluoroborate) (Selectfluor), and N-fluoropyridinium salts and multimers thereof, and more preferably 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2,2,2]octane bis(tetrafluoroborate) (Selectfluor).

[0107] The compound (C) can be used alone or in combination of two or more.

[0108] The amount of compound (C) used is not particularly limited. The lower limit of the amount of compound (C) used can be, for example, 0.1 mol or more, preferably 0.2 mol or more, more preferably 0.3 mol or more, even more preferably 0.4 mol or more, and particularly preferably 0.5 mol or more, relative to 1 mol of compound (1). The upper limit of the amount of compound (C) used can be, for example, 10 mol or less, preferably 9 mol or less, more preferably 8 mol or less, even more preferably 7 mol or less, and even more preferably 6 mol or less, relative to 1 mol of compound (1). The amount of compound (C) used can be, for example, within a range of 0.1 to 10 mol, preferably within a range of 0.2 to 9 mol, more preferably within a range of 0.3 to 8 mol, even more preferably within a range of 0.4 to 7 mol, and even more preferably within a range of 0.5 to 6 mol, relative to 1 mol of compound (1).

[0109] It is also preferable that compound (C) is used in an amount in which the number of F atoms on N atoms in compound (C) exceeds 1 mole (for example, in a range of 1.1 to 3 moles, in a range of 1.2 to 2.5 moles, or in a range of 1.3 to 2 moles) per mole of compound (1).

[0110] From the viewpoint of production costs, it is preferable to recover and reuse the compound (C) remaining after the reaction.

[0111] The fluorine source (A), the iodine source (B), and the compound (C) may be added to the reaction system separately or all at once (for example, in the form of a composition described below).

[0112] In a preferred embodiment of the manufacturing method of the present disclosure, the fluorine source (A) is hydrogen fluoride, the iodine source (B) is iodine or tetrabutylammonium iodide, and the compound (C) is 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2,2,2]octane bis(tetrafluoroborate) (Selectfluor) or 1,1′-difluoro-2,2′-bipyridinium bis(tetrafluoroborate) (Synfluor).

[0113] The reaction in step A can be carried out in the presence or absence of a solvent. The solvent may be either a nonpolar solvent or a polar solvent. The solvent may be an ester, a ketone, an aromatic hydrocarbon, an alcohol, an ether, an amine, a nitrogen-containing polar organic compound, a nitrile, a halogenated hydrocarbon, an aliphatic hydrocarbon, a fluorinated solvent, a carbonate, or other solvent, or a combination thereof.

[0114] Examples of the ester as the solvent include ethyl acetate, butyl acetate, amyl acetate, ethylene glycol monomethyl ether acetate, propylene glycol monomethyl ether acetate, and a preferred example thereof is ethyl acetate.

[0115] Examples of ketones as the solvent include acetone, methyl ethyl ketone, diethyl ketone, hexanone, methyl isobutyl ketone, heptanone, diisobutyl ketone, acetonylacetone, methylhexanone, and acetophenone, cyclohexanone, diacetone alcohol, and a preferred example thereof is acetone.

[0116] Examples of aromatic hydrocarbons as the solvent include benzene, toluene, xylene, and ethylbenzene, and preferred examples thereof include benzene and toluene.

[0117] Examples of the alcohol as the solvent include methanol, ethanol, n-propanol, isopropanol, n-butanol, pentanol, hexanol, ethylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, tripropylene glycol, polypropylene glycol, trimethylene glycol, and hexanetriol, and preferred examples thereof include methanol and ethanol.

[0118] Examples of the ether as the solvent include diethyl ether, dibutyl ether, tetrahydrofuran, tetrahydropyran, dioxane, dimethoxyethane, diethylene glycol diethyl ether, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, propylene glycol monomethyl ether (PGME; also known as 1-methoxy-2-propanol), propylene glycol monoethyl ether, triethylene glycol dimethyl ether, triethylene glycol diethyl ether, tetraethylene glycol dimethyl ether, tetraethylene glycol diethyl ether, and anisole, and preferred examples thereof include diethyl ether and tetrahydrofuran.

[0119] Examples of the amine solvent include monoethanolamine, diethanolamine, and triethanolamine.

[0120] Examples of the nitrogen-containing polar organic compound as the solvent include N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidone, 2-pyrrolidone, and 1,3-dimethyl-2-imidazolidinone, and preferred examples thereof include N,N-dimethylformamide, N,N-dimethylacetamide, and N-methyl-2-pyrrolidone.

[0121] Examples of the nitrile as the solvent include acetonitrile, propionitrile, butyronitrile, isobutyronitrile, benzonitrile, and adiponitrile, and a preferred example thereof is acetonitrile.

[0122] Examples of halogenated hydrocarbons as the solvent include dichloromethane, dichloroethane, chloroform, carbon tetrachloride, tetrachloroethane, trichloroethane, chlorobenzene, dichlorobenzene, and chlorotoluene, and preferred examples thereof include dichloromethane and chloroform.

[0123] Examples of aliphatic hydrocarbons as the solvent include hexane, cyclohexane, heptane, octane, nonane, decane, undecane, dodecane, and mineral spirits, and preferred examples thereof include cyclohexane and heptane.

[0124] Examples of the fluorine-based solvent include perfluorobenzene, trifluorotoluene, ditrifluorobenzene, and trifluoroethanol, and preferred examples thereof include perfluorobenzene and trifluoroethanol.

[0125] Examples of carbonates as the solvent include tetralin dimethyl carbonate, methyl ethyl carbonate, diethyl carbonate, ethylene carbonate, and propylene carbonate, and preferred examples thereof include ethylene carbonate and propylene carbonate.

[0126] Examples of such other solvents include acetic acid, pyridine, dimethyl sulfoxide, sulfolane, and water.

[0127] The solvent may preferably be at least one selected from aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons, and nitriles, more preferably at least one selected from halogenated hydrocarbons and nitriles, and even more preferably halogenated hydrocarbons.

[0128] The solvents may be used alone or in combination of two or more.

[0129] The amount of the solvent used may be, for example, usually within a range of 0 to 200 parts by mass, preferably within a range of 1 to 100 parts by mass, and more preferably within a range of 5 to 50 parts by mass, relative to 1 part by mass of compound (1).

[0130] Each component may be added to the reaction system in step A all at once, in several batches, or continuously.

[0131] 2-6. Temperature and Time The temperature in step A is usually in the range of 0 to 200°C, preferably in the range of 10 to 100°C, more preferably in the range of 20 to 100°C, and even more preferably in the range of 40 to 60°C.

[0132] The time for step A can usually be within the range of 0.1 to 72 hours, preferably within the range of 0.5 to 48 hours, and more preferably within the range of 1 to 36 hours.

[0133] 2-7. Optional Additional Step B The method for producing a fluorine adduct of compound (1) may further include step B of isolating or purifying compound (1), in addition to step A. Isolation or purification of compound (1) can be carried out by a method such as filtration, extraction, stripping, dissolution, concentration, precipitation, dehydration, adsorption, or chromatography, or a combination thereof.

[0134] In one embodiment, step B is a step of separating compound (C) and / or a derivative thereof from the reaction mixture obtained by the reaction of step A. The separation step is preferably a step of reducing the reaction mixture with a reducing agent. By such a reduction treatment, compound (C) and / or a derivative thereof can be separated simply and to a high degree.

[0135] Examples of the reducing agent include sulfur-based reducing agents, and preferred examples thereof include hydrogen sulfites, sulfites, and thiosulfates. Examples of hydrogen sulfites include ammonium hydrogen sulfite and alkali metal hydrogen sulfites such as sodium hydrogen sulfite and potassium hydrogen sulfite. Examples of sulfites include alkali metal sulfites such as sodium sulfite and potassium sulfite. Examples of thiosulfates include alkali metal thiosulfates such as sodium thiosulfate and potassium thiosulfate.

[0136] The reducing agents may be used alone or in combination of two or more.

[0137] In another embodiment, step B is a step of isolating or purifying compound (1) by separating or removing the fluorine source (A), the iodine source (B), compound (C), and / or derivatives thereof from the reaction mixture obtained by the reaction of step A. This step can be carried out by a simple method such as extraction, back-extraction, or water washing. This step can also reduce the load of column chromatography and distillation, which are necessary when an organic iodine compound is used, and therefore can significantly reduce the cost required for producing compound (1). Specifically, the method for producing a difluorinated product of compound (1) can reduce the distillation time, the amount of adsorbent packed in the column, and the amount of solvent.

[0138] 3. Composition The composition of the present disclosure comprises (B) at least one iodine source selected from iodine and ammonium iodide, and (C) a compound having at least one fluorinated quaternary nitrogen atom in the molecule (provided that when the iodine source (B) is iodine, the compound (C) is not an N-fluoropyridinium salt or a polymer thereof).

[0139] Examples of the iodine source (B) and the compound (C) include those exemplified in the above section "2-2. Production method for a fluorine adduct of compound (1)." In the above composition, the iodine source (B) is preferably ammonium iodide.

[0140] In one embodiment, the composition further comprises (A) at least one fluorine source selected from hydrogen fluoride, a hydrogen fluoride salt, and a fluoride salt. Examples of the fluorine source (A) include those exemplified in "2-2. Method for producing a fluorine adduct of compound (1)" above.

[0141] In the composition, the lower limit of the content of the fluorine source (A) can be, for example, 0.1 mol or more, 0.2 mol or more, or 0.3 mol or more relative to 1 mol of the compound (C). The upper limit of the content of the fluorine source (A) can be, for example, 600 mol or less, 500 mol or less, 400 mol or less, 300 mol or less, 200 mol or less, 100 mol or less, 90 mol or less, 80 mol or less, or 70 mol or less relative to 1 mol of the compound (C). In the composition, the fluorine source (A) is contained in an amount, for example, within a range of 0.1 to 600 mol, preferably within a range of 0.2 to 300 mol, and more preferably within a range of 0.3 to 70 mol, relative to 1 mol of the compound (C).

[0142] In the composition, the lower limit of the content of the iodine source (B) can be, for example, 0.001 mol or more, 0.005 mol or more, 0.01 mol or more, 0.02 mol or more, 0.05 mol or more, or 0.1 mol or more relative to 1 mol of the compound (C). The upper limit of the content of the iodine source (B) can be, for example, 1 mol or less, 0.9 mol or less, 0.8 mol or less, 0.7 mol or less, 0.6 mol or less, 0.5 mol or less, 0.4 mol or less, 0.3 mol or less, 0.2 mol or less, or 0.1 mol or less relative to 1 mol of the compound (C). In the composition, the iodine source (B) is contained in an amount, for example, within a range of 0.001 to 1 mol, preferably within a range of 0.005 to 0.4 mol, and more preferably within a range of 0.01 to 0.2 mol, relative to 1 mol of the compound (C).

[0143] The composition can be suitably used as a fluorinating agent (particularly, a fluorinating agent for compounds having a carbon-carbon double bond or triple bond such as compound (1)). Therefore, the present disclosure encompasses a fluorinating agent (particularly, a fluorinating agent for compounds having a carbon-carbon double bond or triple bond such as compound (1)) comprising the composition.

[0144] In the above composition, the fluorine source (A), the iodine source (B), and the compound (C) can be added to the reaction system all at once, or they can be separated and removed all at once.

[0145] Hereinafter, one embodiment of the present disclosure will be described in more detail by way of examples, but the present disclosure is not limited thereto.

[0146] Example 1a: To a solution of 1-dodecene (0.3 mmol) and iodine (0.03 mmol) in dichloroethane (DCE) (1 mL), triethylamine (TEA)-5HF (0.5 mL, approximately 12 mmol HF) and Selectfluor™ (0.6 mmol) were added and reacted at 40°C for 22 hours. The reaction mixture was poured into a saturated aqueous solution of sodium bicarbonate, followed by the addition of sodium sulfite. The product was extracted three times with dichloromethane, dried over anhydrous sodium sulfate, and the solvent was removed using an evaporator. Methyl 4-fluorobenzoate was added as an internal standard to determine the yield of 1,2-difluorododecane. 19 Analysis by F NMR showed it to be 52%.

[0147] Example 1b The same procedure as in Example 1a was carried out except that the reaction temperature was changed from 40°C to 50°C, thereby obtaining 1,2-difluorododecane in a yield of 67%.

[0148] Example 1c The same procedure as in Example 1a was carried out except that the reaction temperature was changed from 40°C to 60°C, thereby obtaining 1,2-difluorododecane in a yield of 69%.

[0149] Example 1d The same procedure as in Example 1a was carried out except that the reaction temperature was changed from 40°C to 70°C, thereby obtaining 1,2-difluorododecane in a yield of 67%.

[0150] [Example 1e] 1,2-Difluorododecane was obtained in a yield of 60% by the same procedure as in Example 1a, except that the reaction temperature was changed from 40°C to 60°C and the amount of iodine used was changed from 0.03 mmol to 0.015 mmol.

[0151] Example 1f 1,2-Difluorododecane was obtained in a yield of 56% by the same procedure as in Example 1a, except that the reaction temperature was changed from 40°C to 60°C and iodine (0.03 mmol) was replaced with tetrabutylammonium iodide (TBAI; 0.03 mmol).

[0152] Example 1g 1,2-Difluorododecane was obtained in a yield of 56% by the same procedure as in Example 1a, except that the reaction temperature was changed from 40°C to 60°C and Selectfluor™ was changed to Synfluor™.

[0153] Comparative Example 1 1,2-difluorododecane was not obtained by the same procedure as in Example 1a, except that iodine was not used.

[0154] Comparative Example 2: 1-iodo-2-fluorododecane was obtained in 100% yield by the same procedure as in Example 1a, except that the amount of iodine used was changed to 0.3 mmol and the reaction was carried out at room temperature for 21 hours. 1,2-Difluorododecane was not obtained.

[0155] Comparative Example 3: Ethyl α-iodo-β-fluorocinnamate was obtained in a yield of 72% by the same procedure as in Example 1a, except that 1-dodecene was replaced with ethyl cinnamate, TEA (triethylamine)·5HF was replaced with Pyr·9HF (33 mmol HF), the amount of iodine used was changed to 0.3 mmol, and the reaction was carried out at room temperature for 21 hours. Ethyl 3,3-difluoro-2-phenylpropanoate was not obtained.

[0156] Example 2a 1,2-Difluorodecane was obtained in a yield of 73% by the same procedure as in Example 1c, except that 1-decene was used instead of 1-dodecene.

[0157] Example 2b Methyl 9,10-difluoroundecenoate was obtained in a yield of 68% by the same procedure as in Example 1c, except that 1-dodecene was replaced with methyl 10-undecenoate.

[0158] Example 2c 10,11-Difluoro-1-undecanol was obtained in a yield of 65% by the same procedure as in Example 1c, except that 1-dodecene was changed to 10-undecen-1-ol.

[0159] Example 2d 2,3-Difluoropropylbenzene was obtained in a yield of 73% by the same procedure as in Example 1c, except that 1-dodecene was changed to allylbenzene.

[0160] Example 2e The same procedure as in Example 1c was carried out except that 1-dodecene was changed to 2-allyltoluene, thereby obtaining 2-(2,3-difluoropropyl)toluene in a yield of 80%.

[0161] Example 2f N-(4,5-difluoropentenyl)phthalimide was obtained in a yield of 61% by the same procedure as in Example 1c, except that 1-dodecene was changed to N-(4-pentenyl)phthalimide.

[0162] Example 2g The same procedure as in Example 1c was carried out except that 1-dodecene was changed to 4-pentenyl benzoate, to give 4,5-difluoropentyl benzoate in a yield of 65%.

[0163] [Example 3a] Pyr·9HF (33 mmol HF) (0.31 mL, 40 mmol HF) and Selectfluor (0.6 mmol) were added to a solution of ethyl cinnamate (0.3 mmol) and iodine (0.03 mmol) in dichloroethane (DCE) (1 mL), and the mixture was allowed to react at 60°C for 70 hours. The reaction mixture was poured into a saturated aqueous solution of sodium bicarbonate, followed by the addition of sodium sulfite. The mixture was then extracted three times with dichloromethane, dried over anhydrous sodium sulfate, and the solvent was removed using an evaporator. Methyl 4-fluorobenzoate was added as an internal standard to determine the yield of ethyl 3,3-difluoro-2-phenylpropanoate. 19 Analysis by F NMR revealed that it was 86%.

[0164] [Example 3b] Ethyl 3,3-difluoro-2-(4-bromophenyl)propanoate was obtained in a yield of 81% by the same procedure as in Example 3a, except that ethyl cinnamate was replaced with ethyl 4-bromocinnamate and the reaction was carried out for 68 hours.

[0165] [Example 3c] Methyl 3,3-difluoro-2-(4-chlorophenyl)propanoate was obtained in a yield of 82% by the same procedure as in Example 3a, except that ethyl cinnamate was changed to methyl 4-chlorocinnamate and the reaction was carried out for 68 hours.

[0166] Example 3d 2,2-Difluoroethylbenzene was obtained in a yield of 35% by the same procedure as in Example 3a, except that ethyl cinnamate was changed to styrene and the reaction was carried out for 22 hours.

[0167] [Example 3e] 1-Bromo-4-(2,2-difluoroethyl)benzene was obtained in a yield of 56% by the same procedure as in Example 3a, except that ethyl cinnamate was changed to 4-bromostyrene and the reaction was carried out for 20 hours.

[0168] [Example 3f] 1-chloro-4-(2,2-difluoroethyl)benzene was obtained in a yield of 64% by the same procedure as in Example 3a, except that ethyl cinnamate was changed to 4-chlorostyrene and the reaction was carried out for 20 hours.

[0169] [Example 4a] An attempt was made to scale up the reaction of Example 1c. TEA (triethylamine)·5HF (1.0 mL, approximately 24 mmol HF) and Selectfluor™ (425 mg, 1.2 mmol) were added to a solution of 1-dodecene (101 mg, 0.6 mmol) and iodine (15.2 mg, 0.06 mmol) in dichloroethane (DCE) (2 mL), and the mixture was allowed to react at 60°C for 22 hours. The reaction mixture was poured into a saturated aqueous solution of sodium bicarbonate, followed by the addition of sodium sulfite. The product was extracted three times with hexane. The organic phases were combined, washed with water, and then washed with saturated brine. The mixture was dried over anhydrous sodium sulfate, and the solvent was removed using an evaporator. The mixture was dried in a desiccator, yielding 129 mg of a colorless oil. Quantitative analysis using methyl 4-fluorobenzoate as an internal standard revealed the following: 1 It was confirmed by H NMR that the product was 1,2-difluorododecane with a purity of 88%. The yield was 92%.

[0170] [Example 4b] The reaction was carried out in the same manner as in Example 4a. After the reaction, the reaction mixture was poured into a saturated aqueous solution of sodium bicarbonate, and then sodium sulfite was added. The product was extracted three times with ether (diethyl ether). The organic phases were combined, washed with water, and then washed with saturated saline. The mixture was dried over anhydrous sodium sulfate, and the solvent was removed using an evaporator. The mixture was dried in a desiccator to obtain 126 mg of a pale yellow oil. Quantitative analysis using methyl 4-fluorobenzoate as an internal standard revealed the following: 1 It was confirmed by H NMR that the product was 1,2-difluorododecane with a purity of 91%. The yield was 93%.

[0171] Comparative Example 4: To a solution of 1-dodecene (67 mg, 0.4 mmol) and 4-iodotoluene (17 mg, 0.08 mmol) in dichloroethane (DCE) (2 mL), triethylamine (TEA)-5HF (1.0 mL, approximately 24 mmol HF) and Selectfluor™ (213 mg, 0.6 mmol) were added, and the mixture was allowed to react at 40°C for 21 hours. The reaction mixture was poured into saturated sodium bicarbonate, followed by the addition of sodium sulfite. The product was extracted three times with ethyl acetate. The organic phases were combined, washed with water, and then washed with saturated saline. The mixture was dried over anhydrous sodium sulfate, the solvent was removed using an evaporator, and the mixture was dried in a desiccator. Methyl 4-fluorobenzoate was added as an internal standard. 1 H NMR and 19 Quantitative analysis by F NMR confirmed that the product was 1,2-difluorododecane with a purity of 68%. The yield was 80%.

Claims

The following formula (1): (In the formula, R １ and R ２ are independently a hydrogen atom or an organic group, or may be taken together with two adjacent carbon atoms to form a ring, n is 1 or 2; symbol: is a double or triple bond. however, When the symbol is a triple bond, n is 1; When the symbol is a double bond, n is 2; Two R's １ may be the same or different from each other, Two R's ２ may be the same or different from each other, or Two R's １ , or two R ２ may form a ring together with the adjacent carbon atom.) A method for producing a difluorinated compound represented by the following formula: The compound represented by formula (1) (A) at least one fluorine source selected from hydrogen fluoride, hydrogen fluoride salts, and fluoride salts; (B) at least one iodine source selected from iodine and ammonium iodide; and (C) A compound having at least one fluorinated quaternary nitrogen atom in the molecule to difluorinate the compound represented by formula (1), The production method, wherein the amount of the iodine source (B) used is less than 1.0 mole per mole of the compound represented by formula (1).

2. The method according to claim 1, wherein the iodine source (B) is iodine. The method according to claim 1, wherein the amount of the iodine source (B) used is 0.2 moles or less per mole of the compound represented by formula (1). The method according to any one of claims 1 to 3, wherein the compound (C) is at least one selected from 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2,2,2]octane bis(tetrafluoroborate), N-fluoropyridinium salts, and multimers thereof. The method according to any one of claims 1 to 3, wherein the compound (C) is 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2,2,2]octane bis(tetrafluoroborate). The method according to any one of claims 1 to 3, wherein the amount of the compound (C) used is within a range of 0.1 to 10 moles per mole of the compound represented by formula (1). The method according to any one of claims 1 to 3, wherein the compound (C) is used in an amount such that the number of F atoms on N atoms in the compound (C) exceeds 1 mole per mole of the compound represented by formula (1). The method according to any one of claims 1 to 3, wherein the fluorine source (A) is hydrogen fluoride. The method according to any one of claims 1 to 3, wherein the amount of the fluorine source (A) used is within a range of 0.1 to 1000 moles per mole of the compound represented by formula (1). the fluorine source (A) is hydrogen fluoride, the iodine source (B) is iodine or tetrabutylammonium iodide, and the compound (C) is 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2,2,2]octane bis(tetrafluoroborate) or 1,1′-difluoro-2,2′-bipyridinium bis(tetrafluoroborate); The method according to any one of claims 1 to 3. The method according to any one of claims 1 to 3, wherein the reaction is carried out in the presence of a solvent. R １ and R ２ are independently a hydrogen atom, an alkyl group which may have one or more substituents, a cycloalkyl 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, a non-aromatic heterocyclic group which may have one or more substituents, a cyano group, a formyl group, R Ａ O-, R Ａ CO-, R Ａ SO ２ -, R Ａ COO-, (R Ａ ) (R Ｂ ) NCO-, R Ａ OCO-, R Ａ CONR Ｂ -, R Ａ OSO ２ -, or (R Ａ ) (R Ｂ ) NSO ２ - (wherein R Ａ and R Ｂ are independently an alkyl group which may have one or more substituents, an aryl group which may have one or more substituents, or an aralkyl group which may have one or more substituents; R １ and R ２ is taken together with two adjacent carbon atoms to form a ring, The method according to any one of claims 1 to 3. (B) at least one iodine source selected from iodine and ammonium iodide; (C) a compound having at least one fluorinated quaternary nitrogen atom in the molecule; (However, when the iodine source (B) is iodine, the compound (C) is not an N-fluoropyridinium salt or a polymer thereof.) 14. The composition of claim 13, further comprising (A) at least one fluorine source selected from hydrogen fluoride, a hydrogen fluoride salt, and a fluoride salt.

14. The composition of claim 13, wherein the iodine source (B) is ammonium iodide. The composition according to claim 13, wherein the content of the iodine source (B) is 0.2 mol or less per 1 mol of the compound (C). A fluorinating agent comprising the composition of any one of claims 13 to 16.

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