Method for producing organic fluorine compounds

Abstract

To provide a method for producing organic fluorine compounds that enables a thorough removal of sulfur-containing substances, or to provide an organic fluorine compound-containing composition that has a low content of sulfur-containing substances.SOLUTION: The present disclosure relates, inter alia, to a method for producing an organic fluorine compound (pf), wherein the production method comprises: [A] a reaction step A for fluorinating an organic sulfur compound (ss) using a fluorinating agent to obtain an organic fluorine compound (pf)-containing composition (α); and [B] a post-treatment step B for reacting a nucleophilic reagent with the composition (α) at a temperature of at least 40°C.SELECTED DRAWING: None

Description

[Technical Field]

[0001] This disclosure relates to methods for producing organofluorine compounds, etc. [Background technology]

[0002] Organic fluorine compounds are produced by applying fluorinating agents such as IF5 to organic compounds containing sulfur atoms. Methods for this were known (Patent Documents 1 and 2). In these methods, the desired organofluorine compound was produced, but sulfur-containing substances generated from the sulfur-containing organic compound (in other words, the raw material compound) were also produced as by-products.

[0003] Remove this sulfur-containing substance to prevent the use of organofluorine compounds (especially fluorinating agents containing IF5). Alkaline treatment was known as a method for purifying the resulting organofluorine compounds. [Prior art documents] [Patent Documents]

[0004] [Patent Document 1] International Publication No. 01 / 96263 [Patent Document 2] International Publication No. 2015 / 141811 [Overview of the project] [Problems that the invention aims to solve]

[0005] While conventional alkaline treatment methods reduce the amount of sulfur-containing substances, further reduction was desired. This disclosure aims to provide a method for producing organofluorine compounds that can highly remove sulfur-containing substances, or to provide an organofluorine compound-containing composition with a low sulfur-containing substance content. [Means for solving the problem]

[0006] This disclosure encompasses the following aspects: Section 1. Process for producing an organofluorine compound (p f ), comprising: [A] a reaction step A of fluorinating an organosulfur compound (s s ) with a fluorinating agent to obtain a composition (α) containing an organofluorine compound (p f ); and [B] a post-treatment step B of reacting the composition (α) with a nucleophilic reagent at a temperature of 40° C or higher . Item 2. The method according to item 1, wherein the reaction in the post-treatment step B is carried out in the presence of water. Item 3. The production method according to item 1 or 2, wherein the fluorinating agent is a fluorinating agent containing fluoride ions. Item 4. The production method according to any one of items 1 to 3, wherein the fluorinating agent is a fluorinating agent containing an oxidizing agent and fluoride ions. Item 5. The production method according to item 4, wherein the oxidizing agent is at least one selected from the group consisting of a halogen-based oxidizing agent and an ammonium salt-based oxidizing agent. Item 6. The oxidizing agent is IF5, bromine trifluoride, formula (3a): X 2 -Z (3a) [wherein, X 2 is a halogen atom, Z is a halogen atom or NZ 1 Z 2 , Z 1 and Z 2 are each independently an organic group, or Z 1 and Z 2 are bonded to each other to form a ring.] 0]compound represented by, and formula (3a'):

Chemical formula

[0007] This disclosure provides a method for producing organofluorine compounds that can highly remove sulfur-containing substances. Furthermore, this disclosure provides an organofluorine compound-containing composition with a low sulfur-containing substance content. [Modes for carrying out the invention]

[0008] The foregoing summary of this disclosure is not intended to describe any of the disclosed embodiments or all implementations of this disclosure. The following description in this disclosure provides more specific examples of the embodiments. In several places in this disclosure guidance is provided through examples, and these examples can be used in various combinations. In each case, the exemplary group can function as a non-exclusive and representative group. All publications, patents, and patent applications cited herein are incorporated herein by direct reference.

[0009] term Unless otherwise specified, symbols and abbreviations used herein should be understood in the context of this specification and in the art to which this disclosure belongs as commonly used. In this specification, the phrase "contains" is used to include the phrases "essentially consist of" and "consist of". The processes, treatments, or operations described herein may be carried out at room temperature unless otherwise specified. In this specification, room temperature may mean a temperature within the range of 10 to 40°C. In this specification, the notation "Cn-Cm" (where n and m are numbers, respectively) means, as is commonly understood by those skilled in the art, that the number of carbon atoms is n or greater and m or less.

[0010] In this specification, "halogen atom" refers to, for example, a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom.

[0011] In this specification, "organic group" means a group formed by removing one hydrogen atom from an organic compound. Examples of such "organic groups" include: Alkyl molecules 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, An aryl group which may have one or more substituents, An aralkyl group which may have one or more substituents, Non-aromatic heterocyclic groups which may have one or more substituents A heteroaryl group which may have one or more substituents, Cyano group, Aldehyde group, RO-, RCO-, RCOO-, RSO2-, ROCO-, and ROSO2- (In these equations, R is independent, Alkyl molecules 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, 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) These are some examples.

[0012] In this specification, "alkyl group" may be a linear alkyl group, a branched alkyl group, or a cyclic alkyl group (e.g., a cycloalkyl group). In this specification, "alkyl group" may be, for example, a C1-C20 alkyl group, a C1-C12 alkyl group, a C1-C6 alkyl group, a C1-C4 alkyl group, or a C1-C3 alkyl group. In this specification, "alkyl group" refers to linear or branched alkyl groups such as methyl group, ethyl group, propyl group (n-propyl group, isopropyl group), butyl group (n-butyl group, isobutyl group, sec-butyl group, tert-butyl group), pentyl group, and hexyl group. In this specification, "alkyl group" refers to cyclic alkyl groups or cycloalkyl groups (e.g., C3-C8 cycloalkyl groups), such as cyclopropyl groups, cyclobutyl groups, cyclopentyl groups, and cyclohexyl groups.

[0013] In this specification, "alkenyl group" can be, for example, a C2-C10 alkenyl group, a C2-C6 alkenyl group, and the like. In this specification, "alkenyl group" refers to linear or branched alkenyl groups such as vinyl group, allyl group, 3-butenyl group, 1-propen-1-yl group, 2-propen-1-yl group, isopropenyl group, 2-buten-1-yl group, 4-penten-1-yl group, and 5-hexen-1-yl group. In this specification, "alkenyl group" refers to cyclic alkenyl groups or cycloalkenyl groups (e.g., C3-C8 cycloalkenyl groups) such as cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, and cycloheptenyl groups.

[0014] In this specification, "alkynyl group" may be, for example, a C2-C10 alkynyl group. In this specification, "alkynyl group" refers to linear or branched alkynyl groups such as ethynyl, 1-propyne-1-yl, 2-propyne-1-yl, 4-pentin-1-yl, and 5-hexyne-1-yl.

[0015] In this specification, the "aryl group" may be, for example, monocyclic, dicyclic, tricyclic, or tetracyclic. In this specification, "aryl group" can be, for example, a C6-C18 aryl group, a C6-C16 aryl group, a C6-C14 aryl group, a C6-C12 aryl group, and the like. In this specification, examples of "aryl group" include phenyl group, 1-naphthyl group, 2-naphthyl group, 2-biphenyl group, 3-biphenyl group, 4-biphenyl group, and 2-anthryl group.

[0016] In this specification, "aryloxy group" may be a group in which an oxygen atom is bonded to an aryl group (aryl group -O-). In this specification, "aryloxy group" may be, for example, a C6-C18 aryloxy group, a C6-C16 aryloxy group, a C6-C14 aryloxy group, a C6-C12 aryloxy group, and the like. In this specification, "aryloxy group" refers to, for example, a phenoxy group, a naphthyloxy group, and the like.

[0017] In this specification, "aralkyl group" can be, for example, a C7-C19 aralkyl group, a C7-C17 aralkyl group, a C7-C15 aralkyl group, a C7-C13 aralkyl group, a C7-C10 aralkyl group, and the like. In this specification, "aralkyl group" refers to, for example, a benzyl group, a phenethyl group, a diphenylmethyl group, a 1-phenylethyl group, a 1-naphthylmethyl group, a 2-naphthylmethyl group, a 2,2-diphenylethyl group, a 3-phenylpropyl group, a 4-phenylbutyl group, a 5-phenylpentyl group, a 2-biphenylylmethyl group, a 3-biphenylylmethyl group, a 4-biphenylylmethyl group, and the like.

[0018] In this specification, the "non-aromatic heterocyclic group" may be, for example, monocyclic, dicyclic, tricyclic, or tetracyclic. In this specification, "non-aromatic heterocyclic group" can be, for example, a non-aromatic heterocyclic group containing, as ring constituent atoms, 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen atoms in addition to carbon atoms. In this specification, the "non-aromatic heterocyclic group" may be saturated or unsaturated. In this specification, "non-aromatic heterocyclic group" can include, for example, tetrahydrofuryl group, oxazolidinyl group, imidazolinyl group, azilidinyl group, azetidinyl group, pyrrolidinyl group, piperidinyl group, azepanyl group, azocanyl group, piperazinyl group, diazepinyl group, diazocanyl group, tetrahydropyranyl group, morpholinyl group, thiomorpholinyl group, 2-oxazolidinyl group, dihydrofuryl group, dihydropyranyl group, and dihydroquinolyl group.

[0019] In this specification, "heteroaryl group" can include, for example, 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).

[0020] In this specification, "5 or 6-membered monocyclic aromatic heterocyclic group" can include, for example, pyrrolyl group, furyl group, thienyl group, pyrazolyl group, imidazolyl group, isoxazolyl group, oxazolyl group, isothiazolyl group, thiazolyl group, triazolyl group, oxadiazolyl group, thiadiazolyl group, tetrazolyl group, pyridyl group, pyridadinyl group, pyrimidinyl group, pyrazinyl group, and the like.

[0021] In this specification, "5-18 member aromatic condensed heterocyclic group" can include, for example, isoindolyl group, indolyl group, benzofuranyl group, benzothienyl group, indazolyl group, benzimidazolyl group, 1,2-benzoisoxazolyl group, benzoxazolyl group, 1,2-benzoisothiazolyl group, benzothiazolyl group, isoquinolyl group, quinolyl group, synnolinyl group, phthalazinyl group, quinazolinyl group, quinoxalinyl group, pyrazolo[1,5-a]pyridyl group, imidazo[1,2-a]pyridyl group, etc.

[0022] In this specification, "RO-" can include alkoxy groups, aryloxy groups (e.g., C6-C18 aryloxy groups such as phenoxy and naphthoxy groups), and aralkyloxy groups (e.g., C7-C19 aralkyloxy groups such as benzyloxy and phenethyloxy groups).

[0023] In this specification, "alkoxy group" may be a group in which an oxygen atom is bonded to an alkyl group (alkyl-O-). In this specification, "alkoxy group" refers to, for example, a C1-C20 alkoxy group, a C1-C12 alkoxy group, a C1-C6 alkoxy group, a C1-C4 alkoxy group, a C1-C3 alkoxy group. These can be linear or branched alkoxy groups such as C3-C8 cycloalkoxy groups, C3-C7 cycloalkoxy groups, or C4-C7 cycloalkyl groups. In this specification, "alkoxy group" refers to, for example, linear or branched alkoxy groups such as methoxyl group, ethoxy group, propoxy group (n-propoxy group, isopropoxy group), butoxy group (n-butoxy group, isotoxy group, sec-butoxy group, tert-butoxy group), pentyloxy group, and hexyloxy group, as well as cyclic alkoxy groups such as cyclopropoxy group, cyclobutoxy group, cyclopentoxy group, and cyclohexoxy group.

[0024] In this specification, "RCO-" can include, for example, alkylcarbonyl groups (e.g., (C1-C10 alkyl)carbonyl groups such as acetyl, propionyl, and butyryl groups), arylcarbonyl groups (e.g., (C6-C18 aryl)carbonyl groups such as benzoyl and naphthoyl groups), and aralkylcarbonyl groups (e.g., (C7-C19 aralkyl)carbonyl groups such as benzylcarbonyl and phenethylcarbonyl groups).

[0025] In this specification, "RCOO-" can include, for example, alkylcarbonyloxy groups (e.g., (C1-C10 alkyl)carbonyloxy groups such as acetyloxy, propionyloxy, and butyryloxy groups), arylcarbonyloxy groups (e.g., (C6-C18 aryl)carbonyloxy groups such as benzoyloxy and naphthoyloxy groups), and aralkylcarbonyloxy groups (e.g., (C7-C19 aralkyl)carbonyloxy groups such as benzylcarbonyloxy and phenethylcarbonyloxy groups).

[0026] In this specification, "RSO2-" can include, for example, alkylsulfonyl groups (e.g., C1-C10 alkylsulfonyl groups such as methylsulfonyl, ethylsulfonyl, and propylsulfonyl groups), arylsulfonyl groups (e.g., C6-C18 arylsulfonyl groups such as phenylsulfonyl and naphthylsulfonyl groups), and aralkylsulfonyl groups (e.g., C7-C19 aralkylsulfonyl groups such as benzylsulfonyl and phenethylsulfonyl groups).

[0027] In this specification, "ROCO-" can include, for example, alkoxycarbonyl groups (e.g., (C1-C10 alkoxy)carbonyl groups such as methoxycarbonyl group, ethoxycarbonyl group, propoxycarbonyl group, etc.), aryloxycarbonyl groups (e.g., (C6-C18 aryloxy)carbonyl groups such as phenoxycarbonyl group, naphthoxycarbonyl group, etc.), and aralkyloxycarbonyl groups (e.g., (C7-C19 aralkyloxy)carbonyl groups such as benzyloxycarbonyl group, phenethyloxycarbonyl group, etc.).

[0028] In this specification, "ROSO2-" can include, for example, alkoxysulfonyl groups (e.g., C1-C10 alkoxysulfonyl groups such as methoxysulfonyl, ethoxysulfonyl, and propoxysulfonyl groups), aryloxysulfonyl groups (e.g., C6-C18 aryloxysulfonyl groups such as phenoxysulfonyl and naphthoxysulfonyl groups), and aralkyloxysulfonyl groups (e.g., C7-C19 aralkyloxysulfonyl groups such as benzyloxysulfonyl and phenethyloxysulfonyl groups).

[0029] In this specification, "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", "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," and "A heteroaryl group which may have one or more substituents" Examples of "substituents" in these formulas are, respectively, halo group, nitro group, cyano group, oxo group, thioxo group, carboxyl group, sulfo group, sulfamoyl group, sulfinamoyl group, sulfenamoyl group, RO-, RCO-, RCOO-, RSO2-, ROCO-, and ROSO2- (wherein R r This is synonymous with the above. ) can be included. Examples of the substituents referred to as "halo groups" include fluoro groups, chloro groups, bromo groups, and iodine groups. The number of substituents can range from one to the maximum number that can be substituted (e.g., 1, 2, 3, 4, 5, 6).

[0030] In this specification, "heterocycloalkyl group" refers, for example, to a cycloalkyl group in which one or more carbon atoms forming the cyclic structure are substituted with a nitrogen atom, an oxygen atom, a sulfur atom, or the like.

[0031] In this specification, "monoalkylamino group" may be, for example, an amino group monosubstituted with a C1-C6 alkyl group.

[0032] In this specification, "dialkylamino group" may be, for example, an amino group disubstituted with the same or different C1-C6 alkyl groups. Examples of dialkylamino groups include dimethylamino group, diethylamino group, and di-n Examples include amino groups disubstituted with C1-C6 alkyl groups such as propylamino group, diisopropylamino group, dibutylamino group, dipentylamino group, dihexylamino group, methylethylamino group, methylpropylamino group, methylbutylamino group, methylpentylamino group, methylhexylamino group, ethylpropylamino group, ethylbutylamino group, ethylpentylamino group, ethylhexylamino group, propylbutylamino group, propylpentylamino group, propylhexylamino group, butylpentylamino group, butylhexylamino group, pentylhexylamino group, etc.

[0033] In this specification, "acylamino group" refers to groups with 1 to 8 carbon atoms, such as formylamino group, benzoylamino group, acetylamino group, propionylamino group, and n-butyrylamino group. Examples include acylamino groups (formylamino group, alkanoylamino group, arylcarbonylamino group).

[0034] In this specification, examples of "alkylthio group" include -S-(C1-C6 alkyl group) (the same as above for C1-C6 alkyl group).

[0035] In this specification, "heterocyclic group" refers to, for example, a monocyclic or bicyclic heterocyclic group having one or more heteroatoms selected from nitrogen, oxygen, and sulfur as ring constituent atoms, such as a piperidyl group, furyl group, thienyl group, imidazolyl group, oxazolyl group, thiazolyl group, pyrrolyl group, pyrrolidinyl group, triazolyl group, benzothiazolyl group, benzimidazolyl group, oxadiazolyl group, thiadiazolyl group, indolyl group, pyrazolyl group, pyridadinyl group, cinolinyl group, quinolyl group, isoquinolyl group, quinoxaliel group, pyrazinyl group, pyridyl group, benzofuryl group, benzothienyl group, tetrazolyl group, etc.

[0036] Among heterocyclic groups, "aromatic heterocyclic groups" include furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrrolyl, triazolyl, benzothiazolyl, benzimidazolyl, oxadiazolyl, thiadiazolyl, indolyl, pyrazolyl, pyridadinyl, sinnolinyl, quinolyl, isoquinolyl, quinoxalinyl, pyrazinyl, pyridyl, benzofuryl, benzothienyl, tetrazolyl, etc., which are monocyclic or bicyclic groups with 5 to 10 members, nitrogen Examples include heteroaryl groups having one or more heteroatoms selected from elemental, oxygen, and sulfur as ring constituent atoms.

[0037] In this specification, "acyl group" refers to a formyl group; an acetyl group, a propionyl group, an n- Examples include linear or branched alkanoyl groups with 2 to 6 carbon atoms, such as butyryl, isobutyryl, valeryl, isovaleryl, and pivaloyl groups; and arylcarbonyl groups with 7 to 15 carbon atoms, such as benzoyl groups.

[0038] In this specification, examples of alkyl groups, aralkyl groups, aryl groups, cycloalkyl groups, heterocycloalkyl groups, and heterocyclic groups in "alkyl sulfinyl group," "aralkyl sulfinyl group," "aryl sulfinyl group," "cycloalkyl sulfinyl group," "heterocycloalkyl sulfinyl group," and "sulfinyl group with heterocyclic group attached" are those mentioned above.

[0039] In this specification, examples of alkyl groups, aralkyl groups, aryl groups, cycloalkyl groups, heterocycloalkyl groups, and heterocyclic groups in "alkylsulfonyl groups," "aralkylsulfonyl groups," "arylsulfonyl groups," "cycloalkylsulfonyl groups," "heterocycloalkylsulfonyl groups," and "sulfonyl groups with heterocyclic groups attached" are those mentioned above.

[0040] In this specification, "ester group" refers to, for example, an acyl-O- group and an alkoxy-CO- group. Here, "acyl" and "alkoxy" refer to the aforementioned "acyl group" and "alkoxy group."

[0041] In this specification, the number of substituents in substituent groups such as "alkyl groups having one or more substituents," "alkoxy groups having one or more substituents," and "alkenyl groups having one or more substituents" can be, for example, 1 to the maximum number of substituents that can be substituted, 1 to 10, 1 to 8, 1 to 6, or 1 to 5, and preferably 1 to 3. The substituents are not particularly limited as long as they are inert substituents in the fluorination reaction with the fluorinating agent described later. Examples of substituents include halogen atoms, C1-C6 alkoxy groups, C1-C6 alkylthio groups, cyano groups, nitro groups, amino groups, hydroxyl groups, C1-C6 alkyl-carbonyloxy groups (e.g., acetoxy), C1-C6 alkoxy-carbonyl groups (e.g., isopropyloxycarbonyl), and C3-C6 cycloalkyl groups (e.g., cyclohexyl). Examples of alkyl groups having halogens include those in which some or all of the hydrogen atoms of the alkyl group are substituted with fluorine atoms.

[0042] In this specification, the number of substituents in "aralkyl group having one or more substituents," "aryl group having one or more substituents," "aryloxy group having one or more substituents," "cycloalkyl group having one or more substituents," "heterocycloalkyl group having one or more substituents," "heterocyclic group having one or more substituents," "monoalkylamino group having one or more substituents," "dialkylamino group having one or more substituents," "acylamino group having one or more substituents," "alkylsulfinyl group having one or more substituents," "aralkylsulfinyl group having one or more substituents," "arylsulfinyl group having one or more substituents," "cycloalkylsulfinyl group having one or more substituents," "heterocycloalkylsulfinyl group having one or more substituents," "sulfinyl group with one or more substituents attached to a heterocyclic group," "alkylsulfonyl group having one or more substituents," "aralkylsulfonyl group having one or more substituents," "arylsulfonyl group having one or more substituents," "cycloalkylsulfonyl group having one or more substituents," "heterocycloalkylsulfonyl group having one or more substituents," and "sulfonyl group with one or more substituents attached to a heterocyclic group" is 1 to Five substituents, preferably one to three, are included. The substituents are not particularly limited as long as they are inert substituents in the fluorination reaction with the fluorinating agent described later. Examples of substituents include C1-C6 alkyl groups, halogen atoms, C1-C6 alkoxy groups, C1-C6 alkylthio groups, cyano groups, nitro groups, amino groups, hydroxyl groups, oxo groups (=O), cyclohexyl groups which may be substituted with 1 to 3 (e.g., 1 or 2) C1-C10 alkyl groups (e.g., C1-C6 alkyl groups), phenyl groups which may be substituted with 1 to 3 (e.g., 1 or 2) substituents (e.g., alkyl groups (e.g., C1-C10 alkyl groups or C1-C6 alkyl groups), halogen atoms (e.g., fluorine atoms or chlorine atoms), etc.), and biphenyl groups which may be substituted with 1 to 3 (e.g., 1 or 2) substituents (e.g., alkyl groups (e.g., C1-C10 alkyl groups or C1-C6 alkyl groups), halogen atoms (e.g., fluorine atoms or chlorine atoms), etc.).

[0043] In this specification, the number of substituents in an "aliphatic 4- to 7-membered ring having one or more substituents" is 1 to 5, preferably 1 to 3. The substituents are not particularly limited as long as they are inert substituents in the fluorination reaction with the fluorinating agent described later. Examples of substituents include C1-C6 alkyl groups, halogen atoms, C1-C6 alkoxy groups, C1-C6 alkylthio groups, cyano groups, nitro groups, amino groups, hydroxyl groups, and carboxyesters. Furthermore, compounds represented by the following formula are also included in the category of substituted aliphatic 4- to 7-membered rings. [ka]

[0044] In this specification, the number of substituents in an "acyl group having one or more substituents" is 1 to 5, preferably 1 to 3. The substituents are not particularly limited as long as they are inert substituents in the fluorination reaction with the fluorinating agent described later. Examples of substituents include halogen-substituted acetyl groups such as chloroacetyl, bromoacetyl, dichloroacetyl, and trifluoroacetyl; alkoxy-substituted acetyl groups such as methoxyacetyl and ethoxyacetyl; alkylthio-substituted acetyl groups such as methylthioacetyl; phenoxyacetyl, phenylthioacetyl, 2-chlorobenzoyl, 3-chlorobenzoyl, and 4-chlorobenzoyl Examples of substituted benzoyl groups include 4-methylbenzoyl group, 4-t-butylbenzoyl group, 4-methoxybenzoyl group, 4-cyanobenzoyl group, and 4-nitrobenzoyl group.

[0045] Method for producing organofluorine compounds In one embodiment, an organofluorine compound (p f The manufacturing method of ) is [A] Organic sulfur compound(s s ) is fluorinated with a fluorinating agent to produce an organofluorine compound (p f Reaction step A to obtain composition (α) containing ) and [B] Post-treatment step B, in which the composition (α) is reacted with a nucleophile at a temperature of 40°C or higher. Includes.

[0046] Reaction step A Composition (α) is an organosulfur compound (s) due to a fluorinating agent. s ) is produced from and organosulfur compounds (s s ) corresponds to organofluorine compounds (p f The composition (α) is not particularly limited as long as it contains a sulfur-containing substance (b) as an impurity. s It may be a crude organic fluorine compound containing a sulfur-containing substance (b s ) From organofluorine compounds (p f ) will be removed.

[0047] The following illustrates the fluorination process in the manufacturing method of this disclosure. This process yields an organofluorine compound (p f ) is also given as an example.

[0048] Organic sulfur compounds(s) s This includes, for example, sulfide compounds (thioether compounds), thiocarbonyl compounds, etc.

[0049] Sulfide compounds (including dithioacetals and dithioketals) are, for example, formed when one or two hydrogen atoms of a methylene group adjacent to a sulfur atom are replaced by fluorine atoms, or when a sulfur atom is replaced by a fluorine atom, resulting in organosulfur compounds (s s ) generate: (a-1) R 3 -CH2-SR 3a → R 3 -CFH-SR 3a → R 3 -CF2-SR 3a (a-2) R 3 -CHR 3b -SR 3a → R 3 -CFR 3b -SR 3a (b-1) R 3 -CO-CH2-SR 3a → R 3 -CO-CFH-SR 3a → R 3 -CO-CF 2 -SR 3a (b-2) R 3 -CO-CHR 3b -SR 3a → R 3 -CO-CFR 3b -SR 3 a (c) R 3c R 3d C=C(SR 3a )2→ R 3c R3d CH-CF2-SR 3a (d) R 3c R 3d C(SR 3a ')(SR 3a '') → R 3c R 3d CF2 (e) R 3 -C(SR 3a )(SR 3a ')(SR 3a '') → R 3 -CF3 (f) R 3 -C(SR 3a )(SR 3a ')-S-R 3e -S-(SR 3a ')(SR 3a )-R 3 → R 3 -CF3

[0050] [wherein, R 3a 、R 3a ', and R 3a '' are the same or different and may each have one or more substituents, 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 represent an aliphatic 4- to 7-membered ring which may have one or more substituents. R 3 and R 3b ​​These may be the same or different alkyl groups, which may have one or more substituents, aralkyl groups, which may have one or more substituents, aryl groups, which may have one or more substituents, alkenyl groups, which may have one or more substituents, cycloalkyl groups, which may have one or more substituents, heterocycloalkyl groups, which may have one or more substituents, heterocyclic groups, which may have one or more substituents, alkoxy groups, which may have one or more substituents, aryloxy groups, which may have one or more substituents, amino groups, monoalkylamino groups, which may have one or more substituents, dialkylamino groups, which may have one or more substituents, acyl groups, acylamino groups, cyano groups, alkylsulfinyl groups, which may have one or more substituents, and one or more substituents. This indicates an aralkylsulfinyl group which may have 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 to which one or more substituents are attached, 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 to which one or more substituents are attached, or R 3 and R 3b These may be bonded together with the carbon atoms to which they are attached, either via heteroatoms or without, to form a 4- to 8-membered ring (the ring may be substituted with one or more substituents selected from the group consisting of halogen atoms, oxo groups, alkyl groups which may have one or more substituents, aralkyl groups which may have one or more substituents, aryl groups which may have one or more substituents, alkenyl groups which may have one or more substituents, cyano groups, and amino groups). R 3c , and R 3d These may have the same or different hydrogen atoms and one or more substituents. R3c and R3d may represent an alkyl group, an optionally substituted aralkyl group, an optionally substituted aryl group, an optionally substituted alkenyl group, an optionally substituted cycloalkyl group, an optionally substituted heterocycloalkyl group, an optionally substituted heterocyclic group, an optionally substituted alkoxy group, an optionally substituted aryloxy group, an optionally substituted monoalkylamino group, an optionally substituted dialkylamino group, an acyl group, or an acylamino group, or R3c and R3d may be bonded together with adjacent carbon atoms to form a saturated or unsaturated aliphatic 4-7 membered ring having one or more substituents (the ring may be substituted with one or more substituents selected from the group consisting of halogen atoms, oxo groups, optionally substituted alkyl groups, optionally substituted aralkyl groups, optionally substituted aryl groups, optionally substituted alkenyl groups, cyano groups, and amino groups). 3e This indicates an alkylene group or an arylene group.

[0051] Examples of sulfide compounds include methyl ethyl sulfide, methyl benzyl sulfide, 2-phenylthioacetic acid, 2-phenylthioacetophenone, C6H5-CO-CH2SCH3, bis(methylthio)methylbenzene, 2-octyl-1,3-dithiane, 2-phenyl-2-trifluoromethyl-1,3-dithiolane, tris(ethylthio)hexane, 4-tris(methylthio)toluene, 2,2-diphenyl-1,3-dithiolane, and the following: Examples include compounds.

[0052] [ka]

[0053] Thiocarbonyl compounds (including thioketones, thioesters, thiocarbonates, thioamides, dithiocarboxylic acid esters, and dithiocarbamates) can be reacted in the following ways, for example: (a) R 6 -C(=S)-R 6a → R 6 -CF2-R 6a (b) R 6 -C(=S)-SR 6b → R 6 -CF2-SR 6a → R 6 -CF3

[0054] [In the formula, R 6 and R 6a These represent, either identically or differently, 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 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 which may have one or more substituents, or an acylamino group which may have the same or different substituents. R 6 and R 6a These may be joined together to form a ring structure. R 6a These are the same or different hydrogen atoms, alkyl groups which may have one or more substituents, This represents 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 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 which may have one or more substituents, and R 6 and R 6a These may be joined together to form a ring structure. R 6b This 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.

[0055] Examples of thiocarbonyl compounds include thiobenzophenone, O-decyl S-methyl dithiocarbonate, O-(4'-pentyl-[1,1'-bi(cyclohexane)]-4-yl)S-methyl dithiocarbonate, N-butyl-N-(methylthio(thiocarbonyl))propanamide, and O-(3,4,5-trifluorophenyl). 4-Chloro-2,6-difluorobenzothioate, O-(3,4,5-trifluorophenyl)2',3,5-trifluoro-4''-propyl-[1,1':4',1''-terphenyl]-4-carbothioate, O-(3,4,5-trifluorophenyl)2',3,5-trifluoro-4''-pentyl-[1,1':4',1''-terphenyl]-4-carbothioate, dithiocarbonate O-(4-isopropylphenyl)S-methyl, dithiocarbonate O-(4-bromophenyl)S-methyl, 4-(((methylthio)carbonothioyl)oxy)benzoic acid Ethyl acid, O-(3-phenylpropyl)S-methyl dithiocarbonate, O-methyl cyclohexanecarbothioate, O-propyl 1-piperidinecarbothioate, methyl dithiobenzoate, O-phenyl thiobenzoate, N,N-dimethylphenylthioamide, ethyl 3-quinoline dithiocarboxylate, trifluoromethanecarboyl naphthalene, N-methyl-N-phenyltrifluoromethane Examples include oamide and N-benzyl-N-phenylheptafluoropropane oamide.

[0056] The fluorinating agent may be, for example, a fluorinating agent containing fluoride ions. Fluorinating agents containing fluoride ions are preferably fluorinating agents containing an oxidizing agent and fluoride ions, more preferably IF 5、 The fluorinating agent may be bromine trifluoride, at least one oxidizing agent selected from the group consisting of compounds represented by the following formula (3a) and compounds represented by the following formula (3a'), and a fluoride ion. IF5 and F Fluorinating agents containing fluoride ions are preferably IF5, and fluoride ions (preferably HF). The fluorinating agent may also contain an amine. X 2 -Z (3a) [In the formula, X 2 It is a halogen atom, Z is a halogen atom or NZ 1 Z 2 And, Z 1 and Z 2 Each of these is independently an organic group, or Z 1 and Z 2 They are joined to each other, forming a ring. Formula (3a'): [ka] [In the formula, X 3 is a halogen atom, ClO4, or NO3. Q1 ~Q 4 Each of these is independently either H or an organic group, and Q 1 ~Q 4 Any two of them may be joined together to form a ring.

[0057] Preferred oxidizing agents include halogenated oxidizing agents and ammonium salt-based oxidizing agents, which may be used individually or in combination of two or more. When an oxidizing agent contains both a halogen atom and an ammonium cation, it is classified as a halogenated oxidizing agent.

[0058] The halogenated oxidizing agent may be an oxidizing agent containing a halogen atom. Examples of halogenated oxidizing agents include IF5, bromine trifluoride, the compound represented by formula (3a), and the compound represented by formula (3a). Examples of compounds represented by a') that contain halogen atoms include IF5, Bromine trifluoride or a compound represented by formula (3a) is preferred.

[0059] X 2 The atom is preferably an iodine atom, a bromine atom, or a chlorine atom, with a bromine atom being more preferred. Z is an iodine atom, a bromine atom, a chlorine atom, or NZ 1 Z 2 It is preferable. Z 1 and Z 2 Each of these is an organic group independently, or Z 1 and Z 2 These are bonded to each other to form a ring. Examples of organic groups include alkyl groups which may have one or more substituents, and acyl groups which may have one or more substituents, with alkylcarbonyl groups and arylcarbonyl groups being preferred. Z 1 and Z 2The ring formed by the bonding of these elements may have one or more substituents. Examples of such rings include pyrrolidine rings, imidazolidine rings, oxopyrrolidine rings, pyridine rings, piperidine rings, isoquinoline rings, quinoline rings, pyrazole rings, imidazole rings, imidazoline rings, benzimidazole rings, triazole rings, and hydantoin rings, with pyrrolidine rings, imidazolidine rings, and oxopyrrolidine rings being preferred. Examples of substituents on such rings include oxo groups and C1-C10 alkyl groups (preferably C1-C4 alkyl groups), with oxo groups and C1-C3 alkyl groups being preferred. The number of substituents can be 0-4, 0-3, 0-2, 1, 0, 2-4, etc.

[0060] Examples of compounds represented by formula (3a) include N-bromosuccinimide (denoted as NBS). Examples include 1,3-dibromo-5,5-dimethylhydantoin (sometimes abbreviated as DBH), ClF, BrF, ICl, IBr, etc., with N-bromosuccinimide and 1,3-dibromo-5,5-dimethylhydantoin being preferred.

[0061] X 3 The atom is preferably an iodine atom, a bromine atom, ClO4, or NO3, with ClO4 or NO3 being more preferred. Q 1 ~Q 4 Each of these is independently either H or an organic group, and Q 1 ~Q 4 Any two of these may be bonded to each other to form a ring. Examples of organic groups include alkyl groups, alkenyl groups, aryl groups, aralkyl groups, and cycloalkyl groups, which may have one or more substituents. Preferred organic groups are alkyl groups which may have one or more substituents, alkenyl groups which may have one or more substituents, and aryl groups which may have one or more substituents. Q 1 ~Q 4Any two of the elements bonded together to form a ring that may have one or more substituents. Examples of such rings include pyridine rings, quinolium rings, isoquinolium rings, pyrrolidine rings, imidazolidine rings, pyrazole rings, and imidazole rings, with pyridine rings, imidazolidine rings, and pyrazole rings being preferred. Examples of substituents on such rings include alkyl groups, alkenyl groups, aryl groups, aralkyl groups, and cycloalkyl groups. The number of substituents can be 0 to 4, 0 to 3, 0 to 2, 1, 0, etc., with 0 to 2 being preferred. Q 1 ~Q 4 Each of these is more preferably an H or a C1-C4 alkyl group which may be substituted with one phenyl group.

[0062] Examples of compounds represented by formula (3a') include NH4Br, NH4I, MeNH3Br, MeNH3I, and Me Examples of halogenated oxidizing agents include 4NBr, Me4NI, Et4NBr, Et4NI, Bu4NBr, Bu4NI, PhMe3NBr, PhMe3NI, PhCH2NMe3I, and NH4ClO4, as well as ammonium salt-based oxidizing agents such as NH4NO3, with NH4ClO4 and NH4NO3 being preferred.

[0063] The fluoride ion may be a compound containing a fluoride ion, for example, HF, KF, KHF2, NaF, CsF, TiF4, LiF, MgF2, CaF2, NH4F, NHMe3F, NHEt3F, NMe4F, NEt4F, NHBu3F Examples include NBu4F, and preferably HF, KHF2, etc.

[0064] Examples of amines include primary amines such as methylamine, ethylamine, propylamine, butylamine, pentylamine, hexylamine, cyclohexylamine, and ethylenediamine; secondary amines such as dimethylamine, diethylamine, dipropylamine, dibutylamine, dipentylamine, dihexylamine, and dicyclohexylamine; trimethylamine, triethylamine (sometimes written as Et3N), diisopropylethylamine, tributylamine, N,N,N',N'-tetramethylethylenediamine, and triphenylamine. Examples include tertiary amines such as diphenylmethylamine; alicyclic amines such as piperidine, piperazine, pyrrolidine, morpholine, N-methylpiperazine, N-methylpyrrolidine, 5-diazabicyclo[4.3.0]nonane-5-ene, and 1,4-diazabicyclo[2.2.2]octane; aromatic amines such as aniline, methylaniline, dimethylaniline, N,N-dimethylaniline, haloaniline, and nitroaniline; and heterocyclic amines such as pyridine, pyromidine, piperazine, quinoline, and imidazole.

[0065] Examples of fluorinating agents include IF5-Et3N-3HF, IF5-Et3N-5HF, IF5-pyridine-HF, NBS(N-bromosuccinimide)-pyridine-9HF, and DBH(1,3-dibromo-5,5-dimethylhydantoide). (n)-pyridine-9HF, BrF3-KHF2, 4-tert-butyl-2,6-dimethylphenyl sulfur trifluoride (e.g., FLUOLEAD®), Et2NSF3 (abbreviation: DAST), (MeOCH2CH2)2NSF3 (abbreviation) Examples include Deoxo-Fluor, 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octanbis(tetrafluoroborate) (e.g., SelectFluor®), etc. Preferably IF5-Et3N-3HF, IF5-Et3N-5HF, IF5-pyridine-HF, NBS-pyridine-9HF, DBH-pyridine-HF These are lysine-9HF and BrF3-KHF2.

[0066] The amount of fluorinating agent used in reaction step A is the starting compound, an organosulfur compound (s s For 1 mole of ), the amount is preferably in the range of 0.01 to 20 moles, more preferably in the range of 0.1 to 10 moles, and even more preferably in the range of 0.1 to 5 moles.

[0067] The reaction temperature in reaction step A is usually around -70°C to 200°C, preferably around -20°C to 120°C, and more preferably around 0°C to 100°C. The reaction time for reaction step A is typically in the range of 0.1 hours to 300 hours, preferably in the range of 0.5 hours to 100 hours, and more preferably in the range of 2 hours to 48 hours.

[0068] Reaction step A can be carried out in the presence or absence of a solvent, and is preferably carried out in the presence of a solvent. The solvents in question include aliphatic solvents such as pentane, hexane, heptane, cyclohexane, and petroleum ether; 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; halogenated aliphatic solvents such as methyl formate, ethyl formate, methyl acetate, ethyl acetate, and vinegar. Ester solvents such as propyl acid, methyl propionate, γ-butyrolactone, and propylene carbonate; nitrile solvents such as acetonitrile and propionitrile; aromatic solvents such as benzene, chlorobenzene, toluene, dichlorobenzene, fluorobenzene, and nitrobenzene; ether solvents such as monoglime, diglime, diethyl ether, dipropyl ether, and tetrahydrofuran; N,N-dimethylformamide (DMF); dimethyl ether Rufoxide (DMSO), water, nitromethane, N,N-diethylformamide, N,N-dimethylacetamide, 1-methyl-2-pyrrolidone, 1,3-dimethyl-2-imidazolidinone (DMI), tetramethylurea, 1,3-dimethylpropyleneurea, hexamethyl Phosphoramides (HMPA) are examples, and they are used alone or in combination of two or more. Preferred solvents are acetonitrile (MeCN), dichloromethane, ethyl acetate (AcOEt), Examples include monoglymes. The amount of solvent used in reaction step A is the starting compound, an organosulfur compound (s s The amount is preferably in the range of 0.1 to 50 parts by mass, and more preferably in the range of 0.5 to 20 parts by mass, per 1 part by mass of ).

[0069] The fluorination in reaction step A results in the formation of an organofluorine compound (p f A composition (α) containing ) is obtained.

[0070] Composition (α) is an organofluorine compound (p f ) and sulfur-containing substances (b s In addition to the above, it may contain one or more other substances. These other substances may be, for example, substances used in the production of organofluorine compounds (e.g., catalysts, bases), by-products, etc.

[0071] The organofluorine compound obtained in reaction step A (p f The resulting liquid containing ) can be used as is in post-processing step B.

[0072] Post-processing step B In post-treatment step B, the organofluorine compound (p) obtained in reaction step A is processed. f A nucleophile is reacted with a composition (α) containing the crude form of (b) at a temperature of 40°C or higher. This process reacts the sulfur-containing substance (b) contained in the crude form with the nucleophile. s ) is reduced.

[0073] Examples of nucleophiles include anion source compounds. Anion source compounds may be compounds that can provide anions in post-treatment step B. Examples of anion source compounds include carbanion source compounds, halogen ion source compounds, and basic compounds. Anion source compounds can be used individually or in combination of two or more.

[0074] Examples of carbanion source compounds include NaCN, KCN, CuCN, Zn(CN)2, n-BuLi, sec-BuLi, t-BuLi, PhLi, EtMgBr, EtMgCl, MeMgBr, MeMgCl, Et2Zn, Me2Zn, Ph2Zn, PhMgBr, and PhMgCl. These are some examples.

[0075] Examples of halogen ion source compounds include sodium chloride, potassium chloride, lithium chloride, hydrochloric acid, sodium bromide, potassium bromide, lithium bromide, hydrobromic acid, sodium fluoride, potassium fluoride, lithium fluoride, hydrofluoric acid, sodium iodide, potassium iodide, lithium iodide, hydroiodic acid, ammonium chloride, ammonium bromide, ammonium iodide, and ammonium fluoride.

[0076] Examples of basic compounds include (1) acetates and carbonates of alkalis or alkaline earth metals. Examples include salts, bicarbonates, sulfates, sulfites, phosphates, hydrogen phosphates, alkoxides, hydroxides, hydrides, thiosulfates, or amide salts, (2) alkali metals, and (3) amines, and at least one selected from the group consisting of these.

[0077] Examples of acetates include sodium acetate, potassium acetate, lithium acetate, rubidium acetate, cesium acetate, magnesium acetate, calcium acetate, and barium acetate. Examples of carbonates include sodium carbonate, potassium carbonate, lithium carbonate, rubidium carbonate, cesium carbonate, magnesium carbonate, calcium carbonate, and barium carbonate. Examples of bicarbonates include sodium bicarbonate, potassium bicarbonate, lithium bicarbonate, rubidium bicarbonate, cesium bicarbonate, magnesium bicarbonate, calcium bicarbonate, and barium bicarbonate.

[0078] Examples of sulfates include sodium sulfate, potassium sulfate, lithium sulfate, rubidium sulfate, cesium sulfate, magnesium sulfate, calcium sulfate, and barium sulfate.

[0079] Examples of sulfites include sodium sulfite, potassium sulfite, lithium sulfite, rubidium sulfite, cesium sulfite, magnesium sulfite, calcium sulfite, and barium sulfite.

[0080] Examples of phosphates include trisodium phosphate, tripotassium phosphate, trilithium phosphate, trirubidium phosphate, tricesium phosphate, trimagnesium phosphate, tricalcium phosphate, and tribarium phosphate.

[0081] Examples of hydrogen phosphates include sodium hydrogen phosphate, potassium hydrogen phosphate, lithium hydrogen phosphate, rubidium hydrogen phosphate, cesium hydrogen phosphate, magnesium hydrogen phosphate, calcium hydrogen phosphate, and barium hydrogen phosphate.

[0082] Examples of alkoxide salts include sodium methoxide, sodium ethoxide, sodium butoxide, potassium methoxide, potassium ethoxide, potassium butoxide, lithium methoxide, and lithium ethoxide. Examples of hydroxide salts include sodium hydroxide, potassium hydroxide, lithium hydroxide, rubidium hydroxide, cesium hydroxide, magnesium hydroxide, calcium hydroxide, and barium hydroxide.

[0083] Examples of hydride salts include sodium hydride, potassium hydride, lithium hydride, and calcium hydride.

[0084] Examples of thiosulfates include sodium thiosulfate, potassium thiosulfate, lithium thiosulfate, rubidium thiosulfate, cesium thiosulfate, magnesium thiosulfate, calcium thiosulfate, and barium thiosulfate.

[0085] Examples of sulfites include sodium sulfite, potassium sulfite, lithium sulfite, rubidium sulfite, cesium sulfite, magnesium sulfite, calcium sulfite, and barium sulfite.

[0086] Examples of amide salts include sodium amide, potassium amide, lithium amide, rubidium amide, cesium amide, magnesium amide, calcium amide, and barium amide.

[0087] Examples of alkali metals include sodium, potassium, and lithium.

[0088] Examples of amines include aliphatic amines, alicyclic amines, aromatic amines, and heterocyclic amines. The amine can preferably be a tertiary amine. Examples of amines include tri Examples include ethylamine, tri(n-propyl)amine, tri(n-butyl)amine, diisopropylethylamine, cyclohexyldimethylamine, pyridine, lutidine, γ-collidine, N,N-dimethylaniline, N-methylpiperidine, N-methylpyrrolidine, and N-methylmorpholine.

[0089] The basic compounds are preferably lithium hydroxide, potassium hydroxide, sodium hydroxide, calcium hydroxide, lithium carbonate, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, cesium carbonate, potassium sulfite (K2SO3), sodium sulfite (Na2SO3), sodium thiosulfate, potassium thiosulfate, ammonia, and the like. The basic compound is more preferably potassium hydroxide, sodium hydroxide, potassium bicarbonate, sodium hydrocarbon, potassium carbonate, potassium sulfite (K2SO3), or sodium carbonate. And so on.

[0090] Examples of basic compounds include inorganic bases. Examples of inorganic bases include lithium hydroxide, potassium hydroxide, sodium hydroxide, calcium hydroxide, lithium carbonate, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, cesium carbonate, potassium sulfite (K2SO3), sodium sulfite (Na2SO3), sodium thiosulfate, and thiosulfate. Examples include potassium sulfate and ammonia.

[0091] Examples of basic compounds include those of formula M m X n Examples of compounds represented by the formula [wherein M is a cation, X is OH, CN, or CO3, m is the valency of X, and n is the valency of M] include: Formula: M m X n In this, M may be, for example, a metal cation or a substituted ammonium, preferably an alkali metal, alkaline earth metal, or quaternary ammonium. M is more preferably one or more metal cations selected from the group consisting of sodium, lithium, and potassium, and even more preferably one or more metal cations selected from the group consisting of sodium and potassium. Examples of quaternary ammonium compounds include tetraalkylammonium compounds (e.g., tetramethylammonium, tetraethylammonium, tetrapropylammonium, tetrabutylammonium, hexadecyltriethylammonium, etc.) and benzyltrialkylammonium compounds (preferably benzyltriC1-C4 alkylammonium compounds).

[0092] The amount of nucleophile in post-processing step B is an organosulfur compound (S S The amount per mole of ) can be, for example, in the range of 0.5 to 100 moles, preferably in the range of 1 to 70 moles, and more preferably in the range of 2 to 50 moles.

[0093] The processing temperature in post-processing step B can preferably be 50°C or higher, and more preferably 60°C or higher. The processing temperature in post-processing step B can be, for example, 200°C or less, preferably 170°C or less, and more preferably 150°C or less. The lower and upper limits may be combined as appropriate. The processing temperature in post-processing step B can be, for example, in the range of 40°C to 200°C, 40°C to 170°C, 60°C to 170°C, and preferably in the range of 50°C to 170°C, more preferably in the range of 60°C to 150°C. Because the processing temperature in post-processing step B is within the above range, sulfur-containing substances (b s It has a strong effect in reducing )

[0094] The processing time for post-processing step B can be, for example, 0.5 hours or more, preferably 1 hour or more, and more preferably 3 hours or more. The processing time for post-processing step B can be, for example, 72 hours or less, preferably 48 hours or less, and more preferably 24 hours or less. The lower and upper limits may be combined as appropriate. The processing time for post-processing step B can be, for example, within the range of 0.5 hours to 72 hours, 0.5 hours to 48 hours, 0.5 hours to 24 hours, etc., and preferably within the range of 1 hour to 48 hours.

[0095] Post-treatment step B can preferably be carried out in the presence of water. For example, post-treatment step B can be carried out by mixing the composition (α) obtained in reaction step A (e.g., the reaction solution obtained in reaction step A) with water in which the nucleophile is dissolved or dispersed, and setting the temperature to a desired level. The amount of water is not particularly limited as long as the reaction with the nucleophile proceeds.

[0096] Post-treatment step B can preferably be carried out in an organic solvent. For example, post-treatment step B can be carried out by mixing the composition (α) obtained in reaction step A (e.g., the reaction solution obtained in reaction step A) with water in which the nucleophile is dissolved or dispersed and an organic solvent, and maintaining the desired temperature conditions. If the composition (α) obtained in reaction step A contains an organic solvent, it is not necessary to add an organic solvent in post-treatment step B, but it is preferable to add one. Post-treatment step B can be more preferably carried out in the presence of water and an organic solvent. For example, post-treatment step B can be carried out by mixing the composition (α) obtained in reaction step A (e.g., the reaction solution obtained in reaction step A) with water and an organic solvent in which the nucleophile is dissolved or dispersed, and setting the temperature to a desired level. In post-treatment step B, stirring is preferable to promote the reaction.

[0097] If post-treatment step B is carried out in an organic solvent, the organic solvent may be organic solvent WS, organic solvent WP, or a solvent containing both organic solvent WS and organic solvent WP. The amount of organic solvent used is not particularly limited as long as post-treatment step B can be carried out, and the organofluorine compound (p) is used at a temperature of 40°C or higher. f The amount should be such that the crude form of ) dissolves. The organic solvent is preferably an organic solvent WS having a solubility in water of 10 [g / 100g - water (20℃)] or higher. By using such an organic solvent, sulfur-containing substances (b s The reduction effect of ) is further improved. Solubility in water is the maximum amount of organic solvent that dissolves in 100g of water at 20°C. An example of the solubility of organic solvents at 20°C is shown in Table 1.

[0098] [Table 1]

[0099] The solubility of the organic solvent WS in water can be, for example, 10 or more, preferably 15 or more, and more preferably 20 or more. The solubility of the organic solvent WS in water is infinite. Larger is even more preferable. Organic solvents WS can be used in appropriate combinations. The solubility of the organic solvent WS in water can be, for example, 10 to infinity, preferably 15 to infinity, and more preferably 20 to infinity.

[0100] Organic solvents used as WS include monoglycerides, acetonitrile, acetone, dioxane (preferably 1,4-dioxane), N-methylpyrrolidone (abbreviated as NMP), diethylene glycol, 3-butene, 2-butanol, tetrahydrofuran (abbreviated as THF), 2-methyl THF, N,N-dimethylformamide (abbreviated as DMF), and dimethylacetamide (abbreviated as DMAc) are preferred. Furthermore, monoglycerides, acetonitriles, acetone, dioxane (preferably 1,4-dioxane), THF, etc., are more preferred.

[0101] The organic solvent can be a mixed solvent of organic solvent WS and organic solvent WP having a solubility in water of less than 10 [g / 100g - water (20℃)]. The solubility of the organic solvent WP in water can be, for example, less than 10, preferably 5 or less, and more preferably 3 or less. The solubility of the organic solvent WP in water can be, for example, 0.01 or higher. The lower and upper limits may be combined as appropriate. The solubility of the organic solvent WP in water can be, for example, in the range of 0.001 to less than 10, preferably in the range of 0.001 to 5, and more preferably in the range of 0.001 to 3.

[0102] Examples of organic solvents used as WPs include toluene, dichloromethane, hexane, heptane, xylene, benzene, diethyl ether, methyl tert-butyl ether (abbreviated as MTBE), and ethyl acetate. Chloroform and cyclopentyl methyl ether (CPME) are preferred, and toluene, dichloromethane, and heptane are more preferred.

[0103] When using a mixed solvent of organic solvents WS and WP, ​​the mass of organic solvent WS in the mixed solvent can be, for example, 0.1 g or more, preferably 0.5 g or more, per gram of mass of organic solvent WP. The mass of the organic solvent WS in the mixed solvent can be, for example, 20 g or less, preferably 10 g or less, per 1 g of organic solvent WP in the mixed solvent. The lower and upper limits may be combined as appropriate. The mass of the organic solvent WS in the mixed solvent can be, for example, in the range of 0.1 g to 20 g, preferably in the range of 0.5 g to 10 g, per gram of the mass of the organic solvent WP in the mixed solvent.

[0104] The reaction solution obtained in post-treatment step B can be subjected to conventional methods such as liquid-liquid separation, extraction, dissolution, concentration, precipitation, dehydration, adsorption, distillation, rectification, chromatography, or a combination thereof, to remove sulfur-containing substances (b s ) The content of organofluorine compounds (p f A crude product of ) is obtained. For example, (1) the reaction solution obtained by reacting the composition (α) with a nucleophile in step B or (2) the organic phase obtained by liquid-liquidating the reaction solution is concentrated to obtain a solid, then the solid is dissolved in a solvent to obtain a solution, and then an organofluorine compound (p f The crude product can be obtained by methods such as precipitating (recrystallization), separating the reaction solution to obtain the organic layer, and removing the solvent from the organic layer under reduced pressure. These additional treatments can be used to obtain organofluorine compounds (p f This allows for further reduction of the sulfur content.

[0105] The step of obtaining the solid can be carried out by known methods, for example, by concentrating the reaction solution or organic phase under reduced pressure.

[0106] The step of obtaining the solvent can be carried out by known methods, for example, by dissolving the solid in an excess amount of a solvent capable of dissolving the solid. The solvent used in the step of obtaining the solvent is the solid There are no particular restrictions as long as it can dissolve the body, but examples include heptane, hexane, methanol, and ethanol.

[0107] Organic fluorine compounds (p f The step of precipitating the organic fluorine compound (p) is, for example, by adding a poor solvent to the solution. f This can be carried out by a method of precipitating ) the poor solvent is an organofluorine compound (p f It is not particularly limited as long as it can precipitate )

[0108] In the recrystallization method described above, the reaction solution or organic phase may be subjected to a subsequent concentration step using a treatment solution obtained by treating it with silica gel, Celite, activated carbon, or the like. Furthermore, in the recrystallization method, the solution is treated with silica gel, Celite, activated carbon, etc., and the subsequent organic fluorine compound (p f ) may be subjected to a precipitation process. The aforementioned treatment with silica gel, etc., can be carried out by any known and appropriate method, for example, by adding silica gel, Celite, activated carbon, etc., to the reaction solution or organic phase and obtaining a separated liquid (e.g., filtrate) by solid-liquid separation (e.g., filtration), or by subjecting the reaction solution or organic phase to column chromatography of silica gel, Celite, activated carbon, etc., to obtain a distillate.

[0109] Composition (β) In composition (β), sulfur-containing substance (b s Since the content of ) is reduced, composition (β) is an organofluorine compound (p f It is useful as a source of ) Composition (β) can preferably be produced by the method for producing organofluorine compounds of the present disclosure.

[0110] In the composition (β), an organic fluorine compound (p f The lower limit of the content of ) can preferably be 80% by mass, more preferably 90% by mass, and even more preferably 95% by mass. The upper limit of the content of the organofluorine compound in composition (β) can be preferably 99.9% by mass, more preferably 99.5% by mass, and even more preferably 99% by mass. The lower and upper limits may be combined as appropriate. The content of the organofluorine compound in composition (β) can preferably be in the range of 80 to 99.9% by mass, more preferably in the range of 90 to 99.5% by mass, and even more preferably in the range of 95 to 99% by mass.

[0111] In the composition (β), the sulfur-containing substance (b s The upper limit of the content of ) can be preferably 10,000 ppm by mass, more preferably 7,000 ppm by mass, and even more preferably 6,000 ppm by mass, as the amount of sulfur, relative to the mass of composition (β). The lower limit of the sulfur-containing substance content in composition (β) can be preferably 0.01 ppm by mass, more preferably 0.1 ppm by mass, and even more preferably 0.5 ppm by mass, as the amount of sulfur relative to the mass of composition (β). The lower and upper limits may be combined as appropriate. The sulfur-containing substance content in composition (β) can be preferably in the range of 0.01 to 10,000 ppm by mass, more preferably in the range of 0.1 to 7,000 ppm by mass, and even more preferably in the range of 0.5 to 6,000 ppm by mass, relative to the mass of composition (β), as a sulfur content.

[0112] In composition (β), sulfur-containing substance (b s The content of ) is expressed as the amount of sulfur, and the content of organofluorine compounds (p f The mass ratio of the content of ) can preferably be 1 / 10 or less, more preferably 1 / 50 or less, and even more preferably 1 / 100 or less. In composition (β), sulfur-containing substance (b s The amount of sulfur in the content of organofluorine compounds (p f The mass ratio of the content of ) can preferably be 1 / 1,000,000 or more, more preferably 1 / 500,000 or more, and even more preferably 1 / 300,000 or more. It can be. The lower and upper limits may be combined as appropriate. In the composition (β), the sulfur-containing substance (b s The amount of sulfur in the content of organofluorine compounds (p f The mass ratio of the content of ) can preferably be in the range of 1 / 1,000,000 to 1 / 10, more preferably in the range of 1 / 500,000 to 1 / 50, and even more preferably in the range of 1 / 300,000 to 1 / 100.

[0113] In this disclosure, examples of methods for analyzing sulfur content include oxidative decomposition and ultraviolet absorption spectroscopy. More specifically, the methods described in the examples are included. [Examples]

[0114] The following describes in more detail one embodiment of the present disclosure by reference to examples, but the present disclosure is not limited thereto. Unless otherwise specified, each operation in the examples was carried out at room temperature without temperature control. In the examples, Et3N represents triethylamine, Me represents methyl, and AcOEt represents ethyl acetate.

[0115] Method for measuring sulfur content The sulfur content in the examples was measured by the following method. Measuring device: Trace Sulfur Analyzer (Ultraviolet Fluorescence Method) (Mitsubishi Chemical Analytech TS-100) Preparation of sample solutions: 10-15 mg of accurately weighed sample and 10 mL of acetone were placed in a glass vial and the sample was dissolved. Alternatively, 10-15 mg of accurately weighed sample can be used directly for sulfur content measurement without dissolving. Preparation of blank solution: I put 10 mL of acetone into a glass vial. measurement: (1) 100 μL of blank solution was placed in a quartz boat that had been preheated twice, and the acetone was allowed to evaporate. (2) The quartz boat was placed in the sample chamber, and the measurement was performed. (3) The sample solution was measured in the same manner as in (1) and (2). If the sample is not dissolved in acetone, the sample can be placed directly into the quartz boat and measured in the same manner as in (1) and (2). Calculation of sulfur content: Based on the peak areas of the blank and sample solutions obtained from the measurements, the sulfur content was calculated using the following formula. S = ((AB)-b) / a×V / Vt / W×1000 S: Sulfur content in the sample (mass fraction ppm) W: Sample mass (mg) V: Amount of solvent used to dissolve the sample (mL) Vt: Volume used for measurement (μL) A: Sample area value B: Blank area value a: Slope of the calibration curve b: Y-intercept of the calibration curve The calibration curve was created using dibutyl disulfide as the standard sample.

[0116] Example 1 3,5,2'-Trifluoro-4''-propyl[1,1';4',1'']terphenyl-4-carbothioic acid 3,4,5-trifluorophenyl ester (185 g, 0.35 mol) is mixed with MeCN (143 g) and monoglyme (103 g). After dissolving in and fluorinating with IF5-Et3N-3HF (150.9 g, 0.39 mol), the obtained To a solution, an aqueous solution prepared by dissolving toluene (206 g), KOH (176.9 g, 3.16 mol), and K2SO3 (187.1 g, 1.18 mol) in water (925.1 g) was added and mixed. The resulting mixture was stirred at 80 °C for 24 hours. The organic layer obtained by separating the liquid after the stirring was filtered, and then the solvent was distilled off under reduced pressure to obtain a crude product of 4-[Difluoro(3,4,5-trifluorophenoxy)methyl]-3,5,2'-trifluoro-4''-propyl[1,1';4',1'']terphenyl (182 g; the content of the target fluorinated compound was 173 g). The sulfur content thereof is shown in Table 2. The sulfur content is shown in Table 2.

[0117] Example 2 By the same molar amounts and operations as in Example 1, from 3,5,2'-Trifluoro-4''-pentyl[1,1';4',1'']terphenyl-4-carbothioic acid 3,4,5-trifluorophenyl ester, a crude product of 4-[Difluoro(3,4,5-trifluorophenoxy)methyl]-3,5,2'-trifluoro-4''-pentyl[1,1';4',1'']terphenyl (186 g; the content of the target fluorinated compound was 182 g) was obtained.

[0118] Example 3 4-Chloro-2,6-difluorothiobenzoic acid 3,4,5-trifluorophenyl ester (255.6 g, 0.75 mol) was dissolved in MeCN (364.2 g) and subjected to a fluorination reaction with IF5-Et3N-3HF (231.3 g, 0.60 mol). Then, an aqueous solution prepared by dissolving toluene (322.5 g), KOH (271.0 g, 4.84 mol), and K2SO3 (286.6 g, 1.8,1 mol) in water (1417.6 g) was added to the resulting solution and mixed. The resulting mixture was stirred at 85°C for 13 hours. After liquid-liquid extraction of the stirred liquid, the organic layer was filtered, and then the solvent was removed under reduced pressure to obtain crude 5-[(4-chloro-2,6-difluorophenyl)difluoromethoxy]1,2,3-trifluorobenzene (266 g; target fluorinated compound content 245 g). The content is shown in Table 2.

[0119] [Table 2]

[0120] Examples 4 and 5 Crude 4-[Difluoro(3,4,5-trifluorophenoxy)methyl]3,5-difluoro-4'-propylbiphenyl was obtained from 3,5-Difluoro-4'-propylbiphenyl-4-carbothioic acid 3,4,5-trifluorophenyl ester using the same procedure as in Example 1. This crude (500 mg, sulfur content: 5321 ppm) was used. The mixture was dissolved in the solvents shown in Table 3, the additives shown in Table 3 were added, and then the mixture was heated and stirred under the conditions shown in Table 3. After cooling, water and heptane were added to extract the organic matter, and the resulting organic layer was concentrated under reduced pressure and dried to obtain white crystals (495 mg; target fluorinated compound content 485 mg). The sulfur content of the obtained white crystals was analyzed. The results are shown in Table 3.

[0121] [Table 3]

[0122] Example 6 Diphenylmethanethione (5 g, 25.3 mmol) was dissolved in CH2Cl2 (100 g), and IF5-Et3N-3 was prepared. After fluorination with HF (11.6 g, 30.3 mmol), the resulting solution was mixed with MeCN (120 g) and KOH. (13.6 g, 242 mmol) and K2SO3 (19.1 g, 121.2 mmol) dissolved in water (65 g) The solution was added. The mixture was stirred at 40°C for 24 hours and then separated. The resulting organic layer was filtered, and the solvent was removed by vacuum distillation to obtain crude difluorodiphenylmethane (4.4 g; target fluorinated compound content 3.74 g). The sulfur content is shown in Table 4.

[0123] Example 7 Methyl N-butyl-N-(1-oxopropyl)carbamodithioate (0.5 g, 2.28 mmol) was dissolved in dichloromethane (10 g), and then fluorinated with IF5-Et3N-3HF (0.87 g, 2.28 mmol). To the obtained solution, aqueous solutions of MeCN (40 g), KOH (6.5 g, 115.2 mmol), and K2SO3 (9.1 g, 57.6 mmol) dissolved in water (30 g) were added. The mixture was stirred at 75-80°C for 3 hours. After liquid-liquid extraction, the resulting organic layer was filtered, and the solvent was removed under reduced pressure to obtain crude N-Butyl-N-trifluoromethylpropionamide (300 mg; target fluorinated compound content 245 mg). Its sulfur content is shown in Table 4.

[0124] Example 8 Using the same molar quantities and procedures as in Example 7, crude 1-Trifluoromethoxydecane and 1-(Difluoro(methylthio)methoxy)decane were obtained from O-decyl S-methyl carbonodithioate (490 mg; 5 mg) The target sample was found to contain 440 mg of fluorinated compounds. Its sulfur content is shown in Table 4.

[0125] Example 9 The same operation as in Example 7 was carried out except that the solvent used in the reaction was changed from dichloromethane to AcOEt. From S-methyl O-(4'-pentylbicyclohexyl-4-yl)carbonodithioate, a crude product of 4-pentyl-4'-trifluoromethoxybicyclohexyl (378 mg; the content of the target fluorinated compound was 310 mg) was obtained. The sulfur content is shown in Table 4.

[0126] Example 10 The same molar amount and operation as in Example 6 were carried out. From 2,2-diphenyl-[1,3]dithiolane, a crude product of difluorodiphenylmethane (5.2 g; the content of the target fluorinated compound was 4.7 g) was obtained. The sulfur content is shown in Table 4. The sulfur content is shown in Table 4.

[0127] Example 11 The same operation as in Example 7 was carried out except that the fluorinating agent used in the reaction was changed from IF5-Et3N-3HF to NBS-pyridine-9HF. From 4'-(difluoro(methylthio)methoxy)-4-pentylbicyclohexyl, a crude product of 4-pentyl-4'-trifluoromethoxybicyclohexyl (650 mg; the content of the target fluorinated compound was 550 mg) was obtained. The sulfur content is shown in Table 4. The sulfur content is shown in Table 4.

[0128]

Table 4

[0129] Example 12 Silica gel (20 g) was added to the organic layer after liquid separation and filtration obtained in Example 1, and the mixture was stirred at room temperature for 30 minutes. After filtration, the obtained organic layer was concentrated under reduced pressure to obtain a crude product (158 g; (the target fluorinated compound A crude product with a mineral content of 156 g and a sulfur content of 99 ppm was obtained. Furthermore, heptane (555 g) was added to the obtained crude product, and a crystallization step was performed to obtain 4-[Difluoro(3,4,5-trifluorophenoxy)methyl]-3,5,2'-trifluoro-4''-propyl[1,1';4',1'']terphenyl (126 g, sulfur content 23 ppm).

[0130] Example 13 The organic layer obtained in Example 1 after liquid-liquid filtration was concentrated under reduced pressure, and the resulting solid was dissolved in heptane (555 g) and then purified using a silica gel column. The heptane was then removed from the distillate under reduced pressure. After concentration, a crystallization step was carried out using ethanol (516 g), and 4-[Difluoro(3,4,5-trifluorophenoxy)methyl]-3,5,2'-trifluoro-4''-propyl[1,1';4',1'']terphenyl (172 g, sulfur-containing) was obtained. A quantity of 1 ppm was obtained.

[0131] Example 14 4-Chloro-2,6-difluorothiobenzoic acid 3,4,5-trifluorophenyl ester (50 mg, 0.147 mmol) was dissolved in dichloromethane (1 g), and fluorinated with BrF3-1.5(KHF2) (74.9 mg, 0.295 mmol). The resulting solution was then mixed with MeCN (4 g) and KOH (99.1 mg, 1.770 mmol). And an aqueous solution of K2SO3 (186.4 mg, 1.180 mmol) dissolved in water (3 g) was added and mixed. The resulting mixture was stirred at 60°C for 3 hours. After the stirring, the liquid was separated and the organic layer was filtered. Next, the solvent was removed by vacuum distillation to obtain crude 5-[(4-chloro-2,6-difluorophenyl)difluoromethoxy]1,2,3-trifluorobenzene (52.2 mg; target fluorinated compound content 48 mg). The sulfur content was 256 ppm.

Claims

【Request 1】 Organic fluorine compounds (p ｆ ) and sulfur-containing substances (b ｓ ) (However, the said sulfur-containing substance (b ｓ ) from the organic fluorine compound (p ｆ ) is excluded. ) and The sulfur-containing substance (b ｓ The content of (a) in terms of sulfur is 7000 mass ppm or less. 【Request 2】 The organic fluorine compound (p ｆ The composition (β) according to claim 1, wherein the content of is 80 mass% or more. 【Request 3】 The sulfur-containing substance (b ｓ The amount of sulfur contained in the organic fluorine compound (p ｆ The composition (β) according to claim 1 or 2, wherein the mass ratio of the content of the stearate to the content of the stearate is 1 / 10 or less. 【Request 4】 The sulfur-containing substance (b ｓ The composition (β) according to any one of claims 1 to 3, wherein the content of is 6000 ppm by mass or less in terms of sulfur. 【Request 5】 The sulfur-containing substance (b ｓ The content of (β) in terms of sulfur is 0.01 ppm by mass or more. [Request 6] The sulfur-containing substance (b ｓ The content of (β) in terms of sulfur is 0.1 ppm by mass or more.