N-fluoroalkoxy compounds and methods for producing the same

Abstract

This invention provides a method for producing N-fluoroalkoxy compounds in a simple process with high yield. [Solution] The present disclosure provides a method for producing an N-fluoroalkoxy compound, comprising the step of obtaining an N-fluoroalkoxy compound by reacting an N-hydroxy compound having a predetermined structure with a sulfinic acid compound represented by RfSO2Na (in formula (1), Rf is a fluoroalkyl group having 1 or more carbon atoms) in the presence of an oxidizing agent, wherein the oxidizing agent is an oxidizing agent other than a copper-containing compound, and the N-fluoroalkoxy compound is a compound having an NO-Rf moiety.

Description

[Technical Field]

[0001] The present invention relates to an N-fluoroalkoxy compound and a method for producing the same. [Background technology]

[0002] N-fluoroalkoxy compounds are useful synthetic intermediates because they are raw materials for the production of fluoroethers, which are important pharmaceutical compounds.

[0003] A representative example of such an N-fluoroalkoxy compound is a compound in which the hydrogen atom of the hydroxyl group of N-hydroxyphthalimide is replaced with a trifluoromethyl group. Such a compound can be produced by the reaction of N-hydroxyphthalimide with sodium trifluoromethanesulfinate (see Non-Patent Literature 1). [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] P. Tang et al.,Nature Communication,2020,11(1),755.Supporting Information [Overview of the Initiative] [Problems that the invention aims to solve]

[0005] This disclosure aims to provide a method for producing N-fluoroalkoxy compounds and to provide N-fluoroalkoxy compounds, as well as a method for producing fluoroether compounds. [Means for solving the problem]

[0006] This disclosure includes the configurations described in the following sections. Item 1 In the presence of an inorganic oxidizing agent, N-hydroxy compounds and, The following general formula (1) RfSO2M (1) (In formula (1), Rf is a fluoroalkyl group having 1 or more carbon atoms, and M is an alkali metal or alkaline earth metal.) Sulfinic acid compounds represented by The process includes a step to obtain an N-fluoroalkoxy compound through a reaction with, The aforementioned N-hydroxy compound is The following general formula (2a)

[0007] [ka]

[0008] (In formula (2a), R 1a This refers to a group containing a carbonyl group or a group containing an aryl group which may have a substituent. R 2a This indicates a group containing a carbonyl group, a group containing an -N=N bond, or a group containing an -N=C- bond. R 1a and R 2a These may bond with each other along with the nitrogen atom to which they are bonded, forming a saturated or unsaturated ring. (The saturated or unsaturated ring may have an aromatic ring, which may have substituents, further bonded to it.) Compounds represented by, The following general formula (2b)

[0009] [ka]

[0010] (In formula (2b), R 3a (This indicates an aryl group which may have a substituent.) Compounds represented by, One or more species selected from the group consisting of, The aforementioned N-fluoroalkoxy compound is a compound having an NO-Rf moiety. Method for producing N-fluoroalkoxy compound. Item 2 The production method according to item 1, wherein the inorganic oxidant is in a solid state under atmospheric pressure and at 25°C atmosphere. Item 3 The production method according to item 1 or 2, wherein the inorganic oxidant is a compound containing a metal. Item 4 The production method according to item 3, wherein the inorganic oxidant is a compound containing cerium. Item 5 The production method according to item 4, wherein the inorganic oxidant is ammonium hexanitratocerate(IV). Item 6 The production method according to any one of items 1 to 5, wherein the reaction is carried out in the presence of a solvent. Item 7 The N-hydroxy compound is N-hydroxysuccinimide or its derivative, N-hydroxyphthalimide or its derivative, 1-hydroxybenzotriazole or its derivative, and 1-hydroxybenzimidazole or its derivative The production method according to any one of items 1 to 6, which is one or more selected from the group consisting of. Item 8 The following general formula (3a)

[0011]

Chemical formula

[0012] (In formula (3a), Rf represents a fluoroalkyl group having 1 or more carbon atoms, and R 1 , R 2 , R 3 , and R 4 each independently represent hydrogen or a monovalent group) An N-fluoroalkoxy compound represented by. Item 9 The following general formula (3b)

[0013] [ka]

[0014] (In formula (3b), Rf represents a fluoroalkyl group having 2 or more carbon atoms, excluding the -C(CF3)2F group, R 5 , R 6 , R 7 , and, R 8 (Each of these represents the same or different hydrogen or monovalent group.) An N-fluoroalkoxy compound represented by [formula]. Item 10 The following general formula (3c)

[0015] [ka]

[0016] (In formula (3c), Rf represents a fluoroalkyl group having 2 or more carbon atoms, excluding the -C(CF3)2F group, R 9 , R 10 , R 11 , and, R 12 (Each of these represents the same or different hydrogen or monovalent group.) An N-fluoroalkoxy compound represented by [formula]. Section 11 The following general formula (3d)

[0017] [ka]

[0018] (In formula (3d), Rf represents a fluoroalkyl group having 2 or more carbon atoms, excluding the -C(CF3)2F group, R 9 , R 10 , R 11 , R 12 , R 14 , R 15 , R 16 , R 17 , and, R 18 (Each of these represents the same or different hydrogen or monovalent group.) An N-fluoroalkoxy compound represented by [formula]. Item 12 The following general formula (4a)

[0019] [ka]

[0020] (In formula (4a), Rf represents a fluoroalkyl group having 2 or more carbon atoms, excluding the -C(CF3)2F group, R 1a , R 2a R in formula (2a) above 1a , R 2a (This is synonymous with...) A compound represented by, The following general formula (4b)

[0021] [ka] (In formula (4b), Rf represents a fluoroalkyl group having 2 or more carbon atoms, excluding the -C(CF3)2F group, R 3a R in equation (2b) above 3a (This is synonymous with...) A method for producing a fluoroether compound, comprising the step of obtaining a fluoroether compound using an N-fluoroalkoxy compound represented by [formula]. Section 13 The following general formula (3c-1)

[0022] [ka] (In formula (3c-1), Rf represents a fluoroalkyl group having 2 carbon atoms, R 9 , R 10 , R 11 , and, R 12 N-fluoroalkoxy compounds represented by (where each represents the same or different hydrogen or monovalent group), The following formula (4) R 13 ―X (4) (In formula (4), X represents a leaving group, R 13(This indicates an alkyl group which may have substituents.) Alkylating agents represented by In response to this, The following general formula (3'c)

[0023] [ka]

[0024] (In formula (3´c), Rf, R 9 , R 10 , R 11 , and, R 12 Rf and R in the above formula (3c-1) are 9 , R 10 , R 11 , and, R 12 This is synonymous with X and R 13 In equation (4), X and R 13 (It is synonymous with...) The process comprises obtaining a benzotriazole salt represented by A method for producing benzotriazole salts. Section 14 General formula (3b) below

[0025] [ka]

[0026] (In formula (3b), Rf represents a fluoroalkyl group having 2 or more carbon atoms, excluding the -C(CF3)2F group, R 5 , R 6 , R 7 , and, R 8 (Each of these represents the same or different hydrogen or monovalent group.) The process comprises a step of obtaining a fluoroether compound using an N-fluoroalkoxy compound represented by [formula]. A method for producing fluoroether compounds. Item 15 The following general formula (3'c)

[0027] [ka]

[0028] (In formula (3'c), Rf represents a fluoroalkyl group having 2 carbon atoms, R 9 , R 10 , R 11 , and, R 12 Each of the following represents the same or different hydrogen or monovalent group, X represents a leaving group, and R 13 (This indicates an alkyl group which may have substituents.) A method for producing a fluoroether compound, comprising the step of obtaining a fluoroether compound using a benzotriazole salt represented by [formula]. Section 16 The following general formula (3'd) [ka] (In formula (3'd), Rf represents a fluoroalkyl group having 2 carbon atoms, R 9 , R 10 , R 11 , R 12 , R 14 , R 15 , R 16 , R 17 , and, R 18 (Each of these represents the same or different hydrogen or monovalent group.) A method for producing a fluoroether compound, comprising the step of obtaining a fluoroether compound using an N-fluoroalkoxy compound represented by [formula]. [Effects of the Invention]

[0029] According to the method for producing N-fluoroalkoxy compounds of this disclosure, N-fluoroalkoxy compounds can be produced in high yield. [Brief explanation of the drawing]

[0030] [Figure 1] The reaction results from Example 6d are shown. [Figure 2] The reaction results from Example 6e are shown. [Modes for carrying out the invention]

[0031] The inventors of the present invention have diligently conducted research to obtain N-fluoroalkoxy compounds in high yield. The method disclosed in Non-Patent Document 1 mentioned above has the problem of low yield, and in particular, the yield deteriorates when the number of carbon atoms in the fluoroalkoxy moiety of the N-fluoroalkoxy compound is two or more.

[0032] This disclosure has been made in view of the above, and aims to provide a method for producing N-fluoroalkoxy compounds in a simple process with high yield. Specifically, the above objective is achieved by reacting a predetermined N-hydroxy compound with a sulfinic acid compound in the presence of a predetermined oxidizing agent.

[0033] Embodiments of the present invention will be described in detail below. In this specification, the expressions "containing" and "including" include the concepts of "containing," "including," "substantially consisting of," and "consisting only of."

[0034] In the numerical ranges described stepwise in this specification, the upper or lower limit of a numerical range in one step can be arbitrarily combined with the upper or lower limit of a numerical range in another step. In the numerical ranges described in this specification, the upper or lower limit of a numerical range may be replaced with values ​​shown in the examples or values ​​that can be uniquely derived from the examples. Furthermore, in this specification, numbers connected by "~" mean a numerical range that includes the numbers before and after "~" as the lower and upper limits.

[0035] 1. Method for producing N-fluoroalkoxy compounds The method for producing the N-fluoroalkoxy compound described herein involves, in the presence of an oxidizing agent, a N-hydroxy compound and the following general formula (1) RfSO2M (1) (In formula (1), Rf is a fluoroalkyl group having 1 or more carbon atoms, and M is an alkali metal or alkaline earth metal.) The process includes a step of obtaining an N-fluoroalkoxy compound by reaction with a sulfinic acid compound represented by [formula]. Hereinafter, this step will be referred to as "Step 1".

[0036] (Inorganic oxidizing agent) The type of oxidizing agent used in step 1 is not particularly limited; for example, a wide range of known inorganic oxidizing agents can be used. The inorganic oxidizing agent is preferably a metal-containing compound, as this allows the reaction to proceed rapidly and yield the N-fluoroalkoxy compound in high yield.

[0037] The inorganic oxidizing agent is preferably in a solid state under atmospheric pressure and at a temperature of 25°C. In this case, the reaction carried out in step 1 can be easily performed, and the yield of the N-fluoroalkoxy compound produced in step 1 can be increased.

[0038] The inorganic oxidizing agent can be a wide range of compounds containing various metals. Examples of such metals include cerium, iron, manganese, chromium, and copper. Cerium is more preferable as the metal because it is highly reactive and can produce a higher yield of the N-fluoroalkoxy compound in step 1. In other words, the inorganic oxidizing agent used in step 1 is more preferably a compound containing cerium.

[0039] Here, as disclosed in Non-Patent Document 1 above, a hypervalent iodine compound is sometimes used as an oxidizing agent, and an inorganic oxidizing agent is sometimes used as an additive (see also Non-Patent Document: Journal of Organic Chemistry 20203, 4434). However, under such reaction conditions, the yield is insufficient, and the hypervalent iodine compound used is expensive. In contrast, when an inorganic oxidizing agent is used alone, the yield of the target N-fluoroalkoxy compound can be greatly improved. In this case, when an inorganic oxidizing agent is used alone, its equivalent weight can be 0.5, 0.8, 1.0, 1.5, 2.0, or 3.0, and the yield is easier to improve in this order. The method for producing the N-fluoroalkoxy compound of this disclosure using an inorganic oxidizing agent is superior to the method using an organic oxidizing agent because impurities derived from the oxidizing agent can be easily removed by post-treatment such as washing with water.

[0040] The cerium-containing compound is not particularly limited as long as it can function as an inorganic oxidizing agent, and for example, a wide range of known cerium-containing compounds can be mentioned. Among these, the cerium-containing compound is preferably ammonium hexanitratocerium(IV)ate.

[0041] When the inorganic oxidizing agent is ammonium hexanitratocerium(IV)ate, the yield of the N-fluoroalkoxy compound produced in step 1 can be particularly high.

[0042] The inorganic oxidizing agent used in step 1 may be just one type, or it may be two or more different types. The inorganic oxidizing agent used in step 1 can be obtained by known manufacturing methods, or it can be obtained from a commercially available product.

[0043] (N-hydroxy compounds) The N-hydroxy compound used in step 1 is one or more compounds selected from the group consisting of compounds represented by the following general formula (2a) and compounds represented by the following general formula (2b).

[0044] [ka]

[0045] [ka]

[0046] In the above equation (2a), R 1a R represents a group containing a carbonyl group or a group containing an aryl group which may have a substituent. 2a R indicates a group containing a carbonyl group, a group containing a -N=N bond, or a group containing a -N=C- bond. 1a and R 2a These may bond to each other along with the nitrogen atom to which they are bonded, forming a saturated or unsaturated ring, and an aromatic ring, which may have substituents, may be further bonded to the saturated or unsaturated ring.

[0047] In equation (2b) above, R 3a This represents an aryl group which may have substituents.

[0048] Here, in formulas (2a) and (2b), the "aryl group" can be monocyclic, bicyclic, tricyclic, or tetracyclic. Unless otherwise specified, the "aryl group" can be a C6-C18 aryl group. Examples of aryl groups include phenyl, 1-naphthyl, 2-naphthyl, 2-biphenyl, 3-biphenyl, 4-biphenyl, and 2-anthuryl.

[0049] In formulas (2a) and (2b), a substituent is: Halo group (F, Cl, Br, I); Nitro group; Cyano group; Oxo group; Thioxo group; sulfo group; Sulfamoyl group; Sulfinamoyl group; Sulfenamoyl group; and organic group, One could list these groups, or one could list groups that encompass each of these groups.

[0050] The aforementioned organic group can be any of the various hydrocarbon groups. In this specification, "hydrocarbon group" can include, for example, alkyl groups, alkenyl groups, alkynyl groups, cycloalkyl groups, cycloalkenyl groups, cycloalkadienyl groups, aryl groups, aralkyl groups, and combinations thereof. The hydrocarbon group may have, for example, 1 to 30 carbon atoms, preferably 20 or less, more preferably 15 or less, even more preferably 10 or less, particularly preferably 6 or less, and may also have 4 or less carbon atoms.

[0051] Furthermore, the organic group may be a haloalkyl group. In this specification, "haloalkyl group" means an alkyl group in which at least one hydrogen atom is substituted with a halogen atom (F, Cl, Br, I). The number of halogen atoms in a "haloalkyl group" can be one or more (e.g., 1 to 3, 1 to 6, 1 to 12, or the maximum number that can be substituted from 1). For example, a haloalkyl group may have 1 to 30 carbon atoms, 1 to 20 carbon atoms, 6 to 20 carbon atoms, 1 to 20 carbon atoms, 1 to 15 carbon atoms, 1 to 12 carbon atoms, 1 to 10 carbon atoms, 1 to 6 carbon atoms, 1 to 4 carbon atoms, 1 to 3 carbon atoms, 6 carbon atoms, 5 carbon atoms, 4 carbon atoms, 3 carbon atoms, 2 carbon atoms, or 1 carbon atom.

[0052] Examples of the haloalkyl groups mentioned above include fluoroalkyl groups, i.e., alkyl groups in which at least one hydrogen atom is substituted with a fluorine atom. The number of fluorine atoms in a "fluoroalkyl group" can be one or more (e.g., 1 to 3, 1 to 6, 1 to 12, or the maximum number that can be substituted from 1). A "fluoroalkyl group" can be, for example, a fluoroalkyl group with 1 to 30 carbon atoms, 1 to 20 carbon atoms, 6 to 20 carbon atoms, 1 to 20 carbon atoms, 1 to 15 carbon atoms, 1 to 12 carbon atoms, 1 to 10 carbon atoms, 1 to 6 carbon atoms, 1 to 4 carbon atoms, 1 to 3 carbon atoms, 6 carbon atoms, 5 carbon atoms, 4 carbon atoms, 3 carbon atoms, 2 carbon atoms, or 1 carbon atom. A "fluoroalkyl group" includes perfluoroalkyl groups.

[0053] Examples of "fluoroalkyl groups" include, for example, fluoromethyl group, difluoromethyl group, trifluoromethyl group (CF3-), 2,2,2-trifluoroethyl group, pentafluoroethyl group (C2F5-), tetrafluoropropyl group (e.g., HCF2CF2CH2-), hexafluoropropyl group (e.g., (CF3)2CH-), nonafluorobutyl group, octafluoropentyl group (e.g., HCF2CF2CF2CF2CH2-), and tridecafluorohexyl group.

[0054] As an example of a compound represented by formula (2a), the compound represented by the following formula (2a-1) can be given.

[0055] [ka]

[0056] The compound represented by formula (2a-1) is, in formula (2a), R 1a R is a group containing a carbonyl group. 2a is a group containing a carbonyl group, 1a and R 2a These are examples of how these elements, along with the nitrogen atom to which they bond, combine to form a saturated ring.

[0057] In equation (2a-1), R 1 , R 2 , R 3 , and, R 4 Each of these is either the same or different hydrogen or monovalent group. The term "monovalent group" here can mean the substituents mentioned above. Therefore, the monovalent group in formula (2a-1) can be the aforementioned hydrocarbon group or haloalkyl group, which are organic groups, and can also be a halo group, nitro group, cyano group, oxo group, thioxo group, sulfo group, sulfamoyl group, sulfinamoyl group, sulfenamoyl group, alkoxy group, amino group, or hydroxyl group.

[0058] It is preferable that R is highly reactive and can increase the yield of the N-fluoroalkoxy compound produced in Step 1. 1 R 2 R 3 and R 4 are hydrogen. In formula (2a-1), when R 1 R 2 R 3 and R 4 are hydrogen, the compound represented by formula (2a-1) is N-hydroxysuccinimide.

[0059] As another example of the compound represented by the above formula (2a), a compound represented by the following formula (2a-2) can be mentioned.

[0060]

Chemical formula

[0061] In the compound represented by formula (2a-2), in formula (2a), R 1a is a group containing a carbonyl group, R 2a is a group containing a carbonyl group, and R 1a and R 2a are bonded to each other together with the nitrogen atom to which they are bonded to form an unsaturated ring.

[0062] In formula (2a-2), R 5 R 6 R 7 and R 8 are each the same or different and are hydrogen or a monovalent group. The monovalent group referred to here can mean the above-mentioned substituents. Therefore, the monovalent groups in formula (2a-2) can include the hydrocarbon group and haloalkyl group which are organic groups, and in addition, a halo group; nitro group; cyano group; oxo group; thioxo group; sulfo group; sulfamoyl group; sulfinamoyl group; sulfenamoyl group; alkoxy group; amino group; hydroxy group.

[0063] Preferably, R is such that it has high reactivity and can increase the yield of the N-fluoroalkoxy compound produced in Step 1. 5 R 6 R 7 and R 8 are hydrogen. In formula (2a-2), when R 5 R 6 R 7 and R 8 are hydrogen, the compound represented by formula (2a-2) is N-hydroxyphthalimide.

[0064] As yet another example of the compound represented by the above formula (2a), a compound represented by the following formula (2a-3) can be cited.

[0065]

Chemical formula

[0066] In the compound represented by formula (2a-3), in formula (2a), R 1a is a group containing an aryl group, R 2a is a group containing a -N=N bond, and it is an example where R 1a and R 2a are bonded to each other together with the nitrogen atom to which they are attached.

[0067] In formula (2a-3), R 9 R 10 R 11 and R 12 are each the same or different and are hydrogen or a monovalent group. The monovalent group referred to here can mean the substituents described above. Therefore, the monovalent groups in formula (2a-3) can include the hydrocarbon group and haloalkyl group which are organic groups, and in addition, a halo group; nitro group; cyano group; oxo group; thioxo group; sulfo group; sulfamoyl group; sulfinamoyl group; sulfenamoyl group; alkoxy group; amino group; hydroxy group.

[0068] R is preferred because it is highly reactive and can increase the yield of the N-fluoroalkoxy compound produced in step 1. 9 No. 2, R 10 is hydrogen, R 11 CF3, R 12 is hydrogen. Note that in equation (2a-3), R 9 , R 10 , R 11 , and, R 12 When is hydrogen, the compound represented by formula (2a-3) is 1-hydroxybenzotriazole. An example of a compound represented by formula (2a-3) is R 9 No. 2, R 10 is hydrogen, R 11 CF3, R 12 Examples of compounds in which hydrogen is present are given.

[0069] Further examples of compounds represented by formula (2a) include compounds represented by the following formula (2a-4).

[0070] [ka]

[0071] The compounds represented by formula (2a-4) are, in formula (2a), R 1a is a group containing an aryl group, R 2a is a group containing a -N=N bond, and R 1a and R 2a These are examples of how these elements bond to each other along with the nitrogen atom to which they bind.

[0072] In equation (2a-4), R 9 , R 10 , R 11 , R 12 , R 14 , R 15 , R 16 , R 17 , and, R 18Each of these is either the same or different hydrogen or monovalent group. The term "monovalent group" here can mean the substituents mentioned above. Therefore, the monovalent groups in formula (2a-4) can include the aforementioned hydrocarbon groups and haloalkyl groups, which are organic groups, as well as other groups such as halo groups, nitro groups, cyano groups, oxo groups, thioxo groups, sulfo groups, sulfamoyl groups, sulfinamoyl groups, sulfenamoyl groups, alkoxy groups, amino groups, and hydroxyl groups.

[0073] R is preferred because it is highly reactive and can increase the yield of the N-fluoroalkoxy compound produced in step 1. 9 No. 2, R 11 , R 15 and R 17 CF3, R 10 , R 12 , R 14 , R 16 , and R 18 is hydrogen. As an example of a compound represented by formula (2a-4), R 9 No. 2, R 11 , R 15 and R 17 CF3, R 10 , R 12 , R 14 , R 16 , and R 18 Examples of compounds in which the hydrogen atom is present include N-hydroxy-2-(3,5-bistrifluoromethylphenyl)-4-nitro-6-trifluoromethyl-benzimidazole.

[0074] Examples of compounds represented by formula (2b) include the compound represented by the following formula (2b-1).

[0075] [ka]

[0076] In equation (2b-1), R 1 , R 2 , R 3 , R 4 , and, R5 Each of these is either the same or different hydrogen or monovalent group. Here, a monovalent group can mean the substituents mentioned above. Therefore, the monovalent group in formula (2b-1) can be the aforementioned hydrocarbon group or haloalkyl group, which are organic groups, and can also be a halo group; nitro group; cyano group; oxo group; thioxo group; sulfo group; sulfamoyl group; sulfinamoyl group; or sulfenamoyl group. For example, a compound represented by formula (2b-1) is R 1 , R 2 , R 3 , R 4 , and, R 5 Examples of compounds in which fluorine is present can be given.

[0077] N-hydroxy compounds are It is preferable that the compound is one or more selected from the group consisting of N-hydroxysuccinimide or its derivatives, N-hydroxyphthalimide or its derivatives, 1-hydroxybenzotriazole or its derivatives, and 1-hydroxybenzimidazole or its derivatives. In this case, the reaction in step 1 proceeds easily, and the yield of the N-fluoroalkoxy compound produced in step 1 is particularly high. A derivative of N-hydroxysuccinimide is, for example, in formula (2a-1), R 1 , R 2 , R 3 , and, R 4 This can mean that the compound is one in which at least one of the elements is not hydrogen. A derivative of N-hydroxyphthalimide is, for example, in formula (2a-2), R 5 , R 6 , R 7 , and, R 8 This can mean that the compound has at least one element other than hydrogen. A derivative of 1-hydroxybenzotriazole is a compound in formula (2a-3) where R 9 , R 10 , R 11 , and, R 12 This can mean that the compound is one in which at least one of the elements is not hydrogen.

[0078] The N-hydroxy compound used in step 1 may be just one type, or it may be two or more different types. The N-hydroxy compound used in step 1 can be obtained by known manufacturing methods, or it can be obtained from a commercially available product.

[0079] (Process 1) In step 1, in the presence of the oxidizing agent, the N-hydroxy compound and the following general formula (1) RfSO2M (1) (In formula (1), Rf is a fluoroalkyl group having 1 or more carbon atoms, and M is an alkali metal or alkaline earth metal.) The reaction is carried out with a sulfinic acid compound represented by [formula]. This yields an N-fluoroalkoxy compound.

[0080] In formula (1), Rf is exemplified by, for example, a fluoroalkyl group having 1 to 20 carbon atoms, preferably a fluoroalkyl group having 1 to 16 carbon atoms, more preferably a fluoroalkyl group having 1 to 12 carbon atoms, and even more preferably a fluoroalkyl group having 1 to 10 carbon atoms. Examples of fluoroalkyl groups include fluoromethyl group, difluoromethyl group, trifluoromethyl group (CF3-), 2,2,2-trifluoroethyl group, pentafluoroethyl group (C2F5-), CF2HCFH-, CF(CF2H)2-, tetrafluoropropyl group (e.g., HCF2CF2CH2-), hexafluoropropyl group (e.g., (CF3)2CH-), CF2HCFHCFH-, CF2HCFHCFHCFHCFH, CFH2CFH-, CFH2CFHCFH-, CFH2CFHCFHCFHCFH, CFH2CFHCFHCFHCFH-, nonafluorobutyl group, octafluoropentyl group (e.g., HCF2CF2CF2CF2CH2-), and tridecafluorohexyl group. The sulfinic acid compounds represented by formula (1) are CF3SO2Na, C2F5SO2Na, C3F7SO2Na, C4F9SO2Na, and C5F 11 SO2Na, C6F 13 SO2Na, C 10 Examples include F21SO2Na.

[0081] In formula (1), Rf is preferably a perfluoroalkyl group. Further, Rf may be a fluoroalkyl group having chlorine. Examples of the fluoroalkyl group having chlorine include CF2ClCFClCF2CF2.

[0082] In formula (1), Rf may be linear or branched.

[0083] The reaction in step 1 may be carried out either in the absence of a solvent or in the presence of a solvent, and is preferably carried out in the presence of a solvent.

[0084] The type of the solvent is not particularly limited. For example, hydrocarbon solvents such as benzene, toluene, and xylene; ketone solvents such as acetone, methyl ethyl ketone, and isophorone; alcohol solvents such as tert-butyl alcohol, benzyl alcohol, phenoxyethanol, phenylpropylene glycol, and hexafluoro-2-propanol; halogenated hydrocarbon solvents such as methylene chloride and chloroform; ether solvents such as 1,2-dimethoxyethane, tetrahydrofuran, 1,4-dioxane, and anisole; ester solvents such as ethyl acetate, propyl acetate, ethyl carbitol acetate, and butyl carbitol acetate; amide solvents such as N,N-dimethylformamide and N,N-dimethylacetamide; carbonate solvents such as dimethyl carbonate, diethyl carbonate, and propylene carbonate; nitrile solvents such as acetonitrile; nitro solvents such as nitromethane, etc. The solvent may be a mixed solvent. For example, it may be a mixed solvent containing two or more organic solvents, or a mixed solvent containing an organic solvent and water.

[0085] The amount of the solvent used is not particularly limited. For example, it can be 2 mL or more, 3 mL or more, 4 mL or more, 5 mL or more, or 6 mL or more with respect to 1 mmol of the sulfinic acid compound represented by the formula (1) used in the reaction of Step 1. The amount of the solvent used is 60 mL or less, 50 mL or less, 40 mL or less, 30 mL or less, or 20 mL or less with respect to 1 mmol of the compound represented by the formula (1). The amount of the solvent used may be, for example, within the range of 2 to 60 mL or within the range of 5 to 50 mL with respect to 1 mmol of the sulfinic acid compound.

[0086] In Step 1, the reaction method is not particularly limited. For example, an N-hydroxy compound, the sulfinic acid compound, the oxidizing agent, and a solvent used as needed can be introduced into an appropriate reaction vessel and stirred, etc. to carry out the reaction. The reaction can be carried out under an inert gas atmosphere such as argon as needed.

[0087] The reaction temperature is not particularly limited and can be selected, for example, within the range of -20 to 100 °C. The reaction time can be appropriately set according to the reaction temperature and is, for example, within the range of 1 minute to 48 hours, preferably within the range of 3 minutes to 24 hours, more preferably within the range of 5 minutes to 12 hours.

[0088] The amount of the oxidizing agent used in Step 1 is not particularly limited. In terms of facilitating the progress of the reaction carried out in Step 1 and increasing the yield of the N-fluoroalkoxy compound produced in Step 1, the amount of the oxidizing agent used can be 0.4 mol or more per mole of the sulfinic acid compound, or may be 0.8 mol or more, preferably 1 mol or more, more preferably 1.5 mol or more, even more preferably 2.0 mol or more, particularly preferably 3.0 mol or more. Also, it is preferably 10 mol or less, more preferably 8 mol or less, further preferably 5 mol or less, and particularly preferably 3 mol or less.

[0089] The amount of the N-hydroxy compound used in step 1 is not particularly limited. In order to facilitate the reaction in step 1 and to increase the yield of the N-fluoroalkoxy compound produced in step 1, the amount of the sulfinic acid compound used per mole of the N-hydroxy compound can be 0.4 moles or more, or it may be 0.8 moles or more, preferably 1 mole or more, more preferably 1.2 moles or more, even more preferably 1.5 moles or more, preferably 10 moles or less, more preferably 8 moles or less, even more preferably 6 moles or less, and particularly preferably 4 moles or less.

[0090] The reaction may be carried out under pressure, atmospheric pressure, or reduced pressure. Furthermore, the reaction may be continuous or in batch mode.

[0091] The above reaction produces a product containing an N-fluoroalkoxy compound. The N-fluoroalkoxy compound is a compound having an NO-Rf moiety. That is, the N-fluoroalkoxy compound has a structure in which the hydrogen atom of the hydroxyl group in the N-hydroxy compound is replaced by Rf in the sulfinic acid compound.

[0092] The product obtained in step 1 (excluding the raw materials) contains 10 mol% or more of an N-fluoroalkoxy compound, preferably 30 mol% or more, more preferably 40 mol% or more, even more preferably 50 mol% or more, and particularly preferably 60 mol% or more.

[0093] The product obtained in step 1 can be subjected to appropriate methods to remove solvents and other substances, thereby obtaining a product containing the N-fluoroalkoxy compound, for example, as a solid. The solid thus collected can then be purified, dried, or otherwise processed using appropriate methods to obtain the target N-fluoroalkoxy compound with high purity.

[0094] The method for producing an N-fluoroalkoxy compound according to this disclosure may consist only of step 1, or it may include other steps besides step 1.

[0095] The method for producing N-fluoroalkoxy compounds described herein allows for the synthesis of N-fluoroalkoxy compounds in high yield by a simple method. In particular, while it has been difficult to obtain N-fluoroalkoxy compounds having a fluoroalkoxy moiety with two or more carbon atoms in high yield conventionally, the method for producing N-fluoroalkoxy compounds described herein makes it possible to obtain N-fluoroalkoxy compounds having a fluoroalkoxy moiety with two or more carbon atoms in high yield.

[0096] The N-fluoroalkoxy compounds obtained by the manufacturing method of this disclosure can be suitably used, for example, as raw materials for synthesizing fluoroethers used as pharmaceutical compounds, and can also be widely applied to various other uses.

[0097] 2. N-Fluoroalkoxy Compounds This disclosure includes N-fluoroalkoxy compounds.

[0098] One embodiment of the N-fluoroalkoxy compound of this disclosure is an N-fluoroalkoxy compound represented by the following general formula (3a).

[0099] [ka]

[0100] In formula (3a) above, Rf represents a fluoroalkyl group having 1 or more carbon atoms, and R 1 , R 2 , R 3 , and, R 4 Each of these represents the same or different hydrogen or monovalent group. More specifically, R in formula (3a) 1 , R 2 , R 3 , and, R 4is synonymous with R in formula (2a-1). 1 R 2 R 3 and R 4 respectively.

[0101] In the formula (3a), Rf is exemplified by a fluoroalkyl group having 1 to 20 carbon atoms, preferably a fluoroalkyl group having 1 to 16 carbon atoms, more preferably a fluoroalkyl group having 1 to 12 carbon atoms, and still more preferably a fluoroalkyl group having 1 to 10 carbon atoms.

[0102] In the formula (3a), Rf is preferably a perfluoroalkyl group. Also, Rf may be a fluoroalkyl group having chlorine. Examples of the fluoroalkyl group having chlorine include CF2ClCFClCF2CF2.

[0103] In the formula (3a), Rf may be linear or branched.

[0104] Another aspect of the N-fluoroalkoxy compound of the present disclosure is an N-fluoroalkoxy compound represented by the following general formula (3b).

[0105]

Chemical formula

[0106] In the formula (3b), Rf represents a fluoroalkyl group having 2 or more carbon atoms excluding the -C(CF3)2F group, and R 5 R 6 R 7 and R 8 each independently represent hydrogen or a monovalent group. More specifically, R 5 R 6 R 7 and R 8 in the formula (3b) are synonymous with R 5 R 6 R 7 and R 8 in the formula (2a-2) respectively.

[0107] In formula (3b) above, Rf is defined as a fluoroalkyl group having 2 to 20 carbon atoms, excluding the -C(CF3)2F group, preferably a fluoroalkyl group having 2 to 16 carbon atoms, more preferably a fluoroalkyl group having 2 to 12 carbon atoms, and even more preferably a fluoroalkyl group having 2 to 10 carbon atoms.

[0108] In formula (3b), Rf is preferably a perfluoroalkyl group. Alternatively, Rf may be a chlorine-containing fluoroalkyl group. Examples of chlorine-containing fluoroalkyl groups include CF2ClCFClCF2CF2.

[0109] In equation (3b), Rf may be linear or branched.

[0110] Another embodiment of the N-fluoroalkoxy compounds of this disclosure is an N-fluoroalkoxy compound represented by the following general formula (3c).

[0111] [ka]

[0112] In formula (3c) above, Rf represents a fluoroalkyl group having 2 or more carbon atoms, excluding the -C(CF3)2F group, and R 9 , R 10 , R 11 , and, R 12 Each of these represents the same or different hydrogen or monovalent group. More specifically, R in formula (3c) 9 , R 10 , R 11 , and, R 12 R in equation (2a-3) is 9 , R 10 , R 11 , and, R 12 These are synonymous with each other. For example, R 9 No. 2, R 10 is hydrogen, R 11 CF3, R 12Examples of compounds in which hydrogen is present are given.

[0113] In formula (3c) above, Rf is defined as a fluoroalkyl group having 2 to 20 carbon atoms, excluding the -C(CF3)2F group, preferably a fluoroalkyl group having 2 to 16 carbon atoms, more preferably a fluoroalkyl group having 2 to 12 carbon atoms, and even more preferably a fluoroalkyl group having 2 to 10 carbon atoms.

[0114] In formula (3c), Rf is preferably a perfluoroalkyl group. Alternatively, Rf may be a chlorine-containing fluoroalkyl group. Examples of chlorine-containing fluoroalkyl groups include CF2ClCFClCF2CF2.

[0115] In formula (3c), Rf may be linear or branched.

[0116] Another embodiment of the N-fluoroalkoxy compounds of this disclosure is an N-fluoroalkoxy compound (benzotriazole salt) represented by the following general formula (3'c).

[0117] [ka]

[0118] In equation (3'c), Rf is R 9 , R 10 , R 11 , and, R 12 In the above equation (3c), Rf is R 9 , R 10 , R 11 , and, R 12 This is equivalent to X indicating a leaving group, and R 13 represents an alkyl group which may have substituents, specifically X and R in formula (4) below. 13 It is synonymous with [the above].

[0119] In formula (3'c), the number of fluorine atoms in Rf is not particularly limited. A specific example of Rf is a perfluoroethyl group.

[0120] In equation (3'c), for example, R 9 No. 2, R 10 is hydrogen, R 11 CF3, R 12 is hydrogen, R 13 Examples of compounds in which the group is a methyl group are given.

[0121] Another embodiment of the N-fluoroalkoxy compounds of this disclosure is an N-fluoroalkoxy compound represented by the following general formula (3d).

[0122] [ka]

[0123] In formula (3d) above, Rf represents a fluoroalkyl group having 2 or more carbon atoms, excluding the -C(CF3)2F group, and R 9 , R 10 , R 11 , R 12 , R 14 , R 15 , R 16 , R 17 , and, R 18 Each of these represents the same or different hydrogen or monovalent group. More specifically, R in formula (3d) 9 , R 10 , R 11 , R 12 , R 14 , R 15 , R 16 , R 17 , and, R 18 R in equation (2a-4) 9 , R 10 , R 11 , R 12 , R 14 , R 15 , R 16 , R 17 , and, R 18 These are synonymous with each other. For example, R 9 No. 2, R11 , R 15 and R 17 CF3, R 10 , R 12 , R 14 , R 16 , and R 18 Examples of compounds in which hydrogen is present are given.

[0124] In formula (3d), Rf is defined as a fluoroalkyl group having 2 to 20 carbon atoms, excluding the -C(CF3)2F group, preferably a fluoroalkyl group having 2 to 16 carbon atoms, more preferably a fluoroalkyl group having 2 to 12 carbon atoms, and even more preferably a fluoroalkyl group having 2 to 10 carbon atoms.

[0125] In formula (3d), Rf is preferably a perfluoroalkyl group. Alternatively, Rf may be a chlorine-containing fluoroalkyl group. Examples of chlorine-containing fluoroalkyl groups include CF2ClCFClCF2CF2.

[0126] In equation (3d), Rf may be linear or branched.

[0127] The N-fluoroalkoxy compounds of this disclosure described above can be suitably used, for example, as raw materials for synthesizing fluoroethers used as pharmaceutical compounds, and can also be widely applied to various other uses.

[0128] The N-fluoroalkoxy compounds of this disclosure described above can be synthesized, for example, by the method for producing the N-fluoroalkoxy compounds of this disclosure.

[0129] 3. Method for producing fluoroether compounds 1 This disclosure includes a method for producing fluoroether compounds. By using the N-fluoroalkoxy compound of the present invention, which is an air-stable etherifying agent, the yield is improved compared to conventional methods, and the yield can be maintained even without sufficient care for humidity and moisture during experimental procedures.

[0130] Method 1 for producing the fluoroether compound in this disclosure is as follows:

[0131] [ka]

[0132] (In formula (4a), Rf represents a fluoroalkyl group having 2 or more carbon atoms, excluding the -C(CF3)2F group, R 1a , R 2a R in formula (2a) above 1a , R 2a (This is synonymous with...) A compound represented by, The following general formula (4b)

[0133] [ka] (In formula (4b), Rf represents a fluoroalkyl group having 2 or more carbon atoms, excluding the -C(CF3)2F group, R 3a R in equation (2b) above 3a (This is synonymous with...) The method comprises a step of obtaining a fluoroether compound using an N-fluoroalkoxy compound represented by [formula].

[0134] One embodiment of the fluoroether compound production method 1 of the present disclosure comprises a step of obtaining a fluoroether compound using an N-fluoroalkoxy compound represented by formula (4a) or (4b). Specifically, the N-fluoroalkoxy compound is reacted with compound C represented by RX, or with an aromatic compound. More specifically, a phthalimide compound having a fluoroalkoxy group on the nitrogen is reacted with compound C represented by RX.

[0135] By reacting an N-fluoroalkoxy compound with compound C represented by RX, the following is obtained: RO-RF A fluoroether compound represented by RX is obtained. Hereafter, the step of reacting the N-fluoroalkoxy compound with compound C represented by RX will be referred to as "Step 2".

[0136] In step 2, it is preferable to use compound C. In compound C, i.e., RX, X represents a leaving group. The leaving group (X) is not particularly limited, and a wide range of known leaving groups can be listed, for example, halogen atoms or halide ions such as Cl, I, and Br, OMs group (Ms is a mesyl group), OTs group (Ts is a tosyl group), and OTf group (Tf is a trifluoromethanesulfonyl group; i.e., the OTf group means a triflat anion).

[0137] In the aforementioned compound C, R is not particularly limited; that is, any known RX used to produce fluoroether compounds can be broadly used in the present invention.

[0138] R can be a monovalent group having an aryl group. Here, the "aryl group" can be monocyclic, dicyclic, tricyclic, or tetracyclic. The aryl group can be, for example, a C6-C18 aryl group. The aryl group can include phenyl, 1-naphthyl, 2-naphthyl, 2-biphenyl, 3-biphenyl, 4-biphenyl, and 2-anthuryl.

[0139] If R is a monovalent group having an aryl group, the aryl group may be a heteroaryl group. Examples of "heteroaryl groups" can include monocyclic aromatic heterocyclic groups (e.g., 5- or 6-membered monocyclic aromatic heterocyclic groups). Examples of "5 or 6-membered monocyclic aromatic heterocyclic groups" 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-pyrrolyl, 3-pyrrolyl, 4-pyrrolyl), 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), thiazolyl This can include compounds such as thiazolyl (e.g., 2-thiazolyl, 4-thiazolyl, 5-thiazolyl), triazolyl (e.g., 1,2,3-triazole-4-yl, 1,2,4-triazole-3-yl), oxadiazolyl (e.g., 1,2,4-oxadiazole-3-yl, 1,2,4-oxadiazole-5-yl), thiadiazolyl (e.g., 1,2,4-thiadiazole-3-yl, 1,2,4-thiadiazole-5-yl), tetrazolyl, pyridyl (e.g., 2-pyridyl, 3-pyridyl, 4-pyridyl), pyridazinil (e.g., 3-pyridazinil, 4-pyridazinil), pyrimidinil (e.g., 2-pyridazinil, 4-pyridazinil, 5-pyridazinil), pyrazinil, etc.

[0140] As an example of R, Ar-COO-(CH2) n - can be listed. Here, n is, for example, a number from 1 to 20, and Ar is the aforementioned aryl group, which may be, for example, a phenyl group.

[0141] Compound C, represented by RX, can be obtained, for example, by known manufacturing methods or from commercially available products.

[0142] The N-fluoroalkoxy compounds represented by formula (4a) or (4b) used in step 2 can specifically include the N-fluoroalkoxy compound represented by formula (3a), the N-fluoroalkoxy compound represented by formula (3b), the N-fluoroalkoxy compound represented by formula (3'c), and the N-fluoroalkoxy compound represented by formula (3'd) described later. That is, an example of the fluoroether compound production method 1 of this disclosure is a method for producing a fluoroether compound that comprises a step of obtaining a fluoroether compound using the N-fluoroalkoxy compound represented by formula (3b).

[0143] In step 2, the reaction conditions between the N-fluoroalkoxy compound and compound C represented by RX are not particularly limited. For example, the reaction temperature can be 25 to 100°C. The reaction time can be appropriately set according to the reaction temperature, for example, 1 to 48 hours. When using the N-fluoroalkoxy compound represented by formula (3b), the above reaction temperature can be preferably adopted.

[0144] In step 2, the amounts of the N-fluoroalkoxy compound and compound C used are not particularly limited; for example, the amount of N-fluoroalkoxy compound used can be 1 to 4 moles per mole of compound C.

[0145] In step 2, the reaction between the N-fluoroalkoxy compound and compound C can also be carried out in a solvent. The solvent is not particularly limited, and examples include the solvents that can be used in step 1 described above.

[0146] In the reaction of step 2, catalysts such as tetrabutylammonium iodide, tetrabutylammonium bromide, and tetrabutylammonium chloride may be present as needed.

[0147] The reaction in step 2 may be carried out under pressure, atmospheric pressure, or reduced pressure. Furthermore, the reaction in step 2 may be a continuous reaction or a batch reaction.

[0148] The reaction in step 2 yields a product containing the fluoroether compound represented by RO-Rf (where Rf is synonymous with Rf in formula (4a) or formula (4b), and also synonymous with Rf in formula (3b)). The product obtained in step 2 (excluding the starting material) contains 10 mol% or more of the fluoroether compound represented by RO-Rf, preferably 30 mol% or more, more preferably 40 mol% or more, even more preferably 50 mol% or more, and particularly preferably 60 moles.

[0149] The product obtained in step 2 can be subjected to appropriate methods to remove solvents and other substances, thereby obtaining a product containing the fluoroether compound, for example, as a solid. The solid thus collected can then be purified, dried, or otherwise processed using appropriate methods to obtain the target fluoroether compound with high purity.

[0150] The method for producing a fluoroether compound according to this disclosure may consist only of step 2, or it may include other steps besides step 2.

[0151] The method for producing fluoroether compounds, including step 2, allows for the synthesis of fluoroether compounds by a simple method. The resulting fluoroether compounds can be used, for example, as pharmaceutical compounds, and can also be widely applied to various other uses.

[0152] 4. Method for producing benzotriazole salts This disclosure includes a method for producing a benzotriazole salt. One embodiment of the method for producing a benzotriazole salt comprises a step of reacting an N-fluoroalkoxy compound represented by the general formula (3c-1) described below with an alkylating agent represented by the general formula (4) described below to obtain a benzotriazole salt represented by the general formula (3'c) described below. Hereinafter, this step will be referred to as "step 3".

[0153] The N-fluoroalkoxy compound used in step 3 is represented by the following general formula (3c-1).

[0154] [ka]

[0155] In formula (3c-1), Rf represents a fluoroalkyl group having 2 carbon atoms, and R 9 , R 10 , R 11 , and, R 12 Each of these represents either the same or different hydrogen atoms or a monovalent group.

[0156] In formula (3c-1), the number of fluorine atoms in Rf is not particularly limited. A specific example of Rf is a perfluoroethyl group.

[0157] In equation (3c-1), R 9 , R 10 , R 11 , and, R 12 These are R in equation (3c), respectively. 9 , R 10 , R 11 , and, R 12 This is synonymous with R. 9 No. 2, R 10 is hydrogen, R 11 CF3, R 12 Examples include N-fluoroalkoxy compounds in which hydrogen is present.

[0158] The alkylating agent used in step 3 is the following general formula (4) R 13 ―X (4) It is represented as follows.

[0159] In equation (4), X represents a leaving group, and R 13 This indicates an alkyl group which may have substituents.

[0160] The leaving group (X) is not particularly limited, and a wide range of known leaving groups can be listed, for example, halogen atoms or halide ions such as Cl, I, and Br, OMs groups (where Ms is a mesyl group), OTs groups (where Ts is a tosyl group), and OTf groups (where Tf is a trifluoromethanesulfonyl group; that is, the OTf group means a triflat anion).

[0161] R 13 In this context, the substituent can be defined as the substituent in formulas (2a) and (2b). 13 For example, the carbon number is 1 or more and 30 or less, preferably 20 or less, more preferably 10 or less, even more preferably 5 or less, and particularly preferably 3 or less. 13 If the group is a methyl group, the alkylating agent becomes a methylating agent.

[0162] R 13 ―Specific examples of X include methyl trifluoromethanesulfonate (R 13 Examples include compounds in which X is a methyl group and X is an OTf group (triflat anion).

[0163] In step 3, the reaction conditions between the N-fluoroalkoxy compound represented by the general formula (3c-1) and the alkylating agent are not particularly limited. For example, the reaction temperature can be 25 to 100°C. The reaction time can be appropriately set according to the reaction temperature, for example, 1 to 60 hours.

[0164] The amounts of N-fluoroalkoxy compound and alkylating agent used in step 3 are not particularly limited; for example, the amount of alkylating agent used can be 1 to 5 moles per mole of N-fluoroalkoxy compound.

[0165] In step 3, the reaction between the N-fluoroalkoxy compound and the alkylating agent can also be carried out in a solvent. The solvent is not particularly limited; for example, the solvents that can be used in step 1 described above can be listed.

[0166] The reaction in step 3 may be carried out under pressure, atmospheric pressure, or reduced pressure. Furthermore, the reaction in step 3 may be a continuous reaction or a batch reaction.

[0167] The product obtained in step 3 contains a benzotriazole salt represented by the following formula (3'c).

[0168] [ka]

[0169] In equation (3'c), Rf, R 9 , R 10 , R 11 , and, R 12 Rf and R in the above formula (3c-1) are 9 , R 10 , R 11 , and, R 12 This is synonymous with X and R 13 In equation (4), X and R 13 It is synonymous with [the above].

[0170] The product obtained in step 3 (excluding the raw materials) contains 10 mol% or more of the benzotriazole salt, preferably 30 mol% or more, more preferably 40 mol% or more, even more preferably 50 mol% or more, and particularly preferably 60 mol% or more.

[0171] The product obtained in step 3 can be subjected to appropriate methods to remove solvents and other substances, thereby obtaining a product containing benzotriazole salt, for example, as a solid. The solid thus collected can be purified, dried, or otherwise processed using appropriate methods to obtain the target benzotriazole salt with high purity.

[0172] The method for producing a benzotriazole salt according to this disclosure may consist only of step 3, or it may include other steps besides step 3.

[0173] 5. Method for producing fluoroether compounds 2 An example of a method 1 for producing a fluoroether compound according to this disclosure is a method 2 for producing a fluoroether compound, which comprises the step of obtaining a fluoroether compound using a salt of a compound having a fluoroalkoxy group on the nitrogen of a nitrogen-containing heterocyclic compound (hereinafter, this step will be referred to as "step 4").

[0174] In step 4, a salt of a compound having a fluoroalkoxy group on the nitrogen of a nitrogen-containing heterocyclic compound is reacted with an aromatic compound. More specifically, a triazole salt having a fluoroalkoxy group on the nitrogen is reacted with an aromatic compound. More specifically, a benzotriazole salt having a fluoroalkoxy group on the nitrogen is reacted with an aromatic compound. In step 4, it is preferable to react the benzotriazole salt represented by formula (3'c) with the aromatic compound. This allows an aromatic compound having an ORf moiety to be obtained. Here, Rf is synonymous with Rf in formula (3'c). Therefore, the product obtained in step 4 has a structure in which the ORf moiety is bonded to the aromatic compound.

[0175] In other words, an example of the fluoroether compound production method 2 of this disclosure is a method for producing a fluoroether compound comprising step 4 of obtaining a fluoroether compound using a benzotriazole salt represented by formula (3'c).

[0176] The aromatic compound used in step 4 is not particularly limited, and for example, any compound having an aryl group can be broadly cited. The aryl group referred to here is the same as the aryl group contained in compound C used in step 2 described above. Therefore, the aryl group in the aromatic compound used in step 4 can be monocyclic, dicyclic, tricyclic, or tetracyclic, and the aryl group may also be the heteroaryl group described above. Examples of aromatic compounds used in step 4 include benzene or benzene having the substituents described below.

[0177] The aromatic compound used in step 4 may have substituents. Such substituents are synonymous with the substituents in formulas (2a) and (2b). The aromatic compound used in step 4 may have, together with or in place of, such a substituent, a -CORa group or a -COORa group. Ra is an organic group, and is synonymous with the organic group in formulas (2a) and (2b). The organic group is preferably a hydrocarbon group, for example, an alkyl group having 1 to 30 carbon atoms, preferably 20 or fewer, more preferably 15 or fewer, even more preferably 10 or fewer, and particularly preferably 6 or fewer.

[0178] In step 4, the reaction conditions between the benzotriazole salt and the aromatic compound are not particularly limited. For example, the reaction temperature can be -20 to 80°C. The reaction time can be set appropriately according to the reaction temperature, for example, from 5 minutes to 12 hours.

[0179] In step 4, the reaction between the benzotriazole salt and the aromatic compound can be irradiated with active energy rays as needed. This allows the reaction between the benzotriazole salt and the aromatic compound to proceed rapidly under mild conditions. Examples of active energy rays include blue LEDs, ultraviolet rays, electron beams, visible light, X-rays, and ion beams, but ultraviolet rays or electron beams are preferred, and ultraviolet rays are particularly preferred, due to their versatility. Examples of ultraviolet light sources that can be used include ultraviolet LEDs, chemical lamps, high-pressure mercury lamps, low-pressure mercury lamps, ultra-high-pressure mercury lamps, metal halide lamps, carbon arcs, xenon arcs, and electrodeless ultraviolet lamps.

[0180] In step 4, the reaction between the benzotriazole salt and the aromatic compound may be carried out in the presence of a catalyst if necessary. The type of catalyst is not particularly limited, and for example, a wide range of known redox catalysts can be mentioned. Examples of redox catalysts include known metal catalysts, and among these, it is preferable that the metal catalyst is a compound containing Ru. Examples of compounds containing Ru include tris(2,2'-bipyridine)ruthenium(II)bis(hexafluorophosphate), (4,4'-di-tert-butyl-2,2'-bipyridine)bis[(2-pyridinyl)phenyl]iridium(III) hexafluorophosphate, tris(1,10-phenanthroline)ruthenium(II)bis(hexafluorophosphate), and tris(1,10-phenanthroline)ruthenium(II) dichloride monohydrate. The amount of catalyst is not particularly limited, and is, for example, 0.1 to 20 mol%, preferably 0.3 to 15 mol%, and more preferably 0.5 to 10 mol%, relative to the benzotriazole salt used in step 4.

[0181] The amounts of benzotriazole salt and aromatic compound used in step 4 are not particularly limited; for example, the amount of aromatic compound used can be 0.7 to 20 moles per mole of benzotriazole salt.

[0182] In step 4, the reaction between the benzotriazole salt and the aromatic compound can also be carried out in a solvent. The solvent is not particularly limited, and examples include the solvents that can be used in step 1 described above.

[0183] The reaction in step 4 may be carried out under pressure, atmospheric pressure, or reduced pressure. Furthermore, the reaction in step 4 may be a continuous reaction or a batch reaction.

[0184] The product obtained in step 4 includes an aromatic compound having an ORf moiety (i.e., an -ORf group). If the aromatic compound is monocyclic, at least one ORf moiety is attached to one aromatic ring, preferably one ORf moiety is attached to one aromatic ring. If the aromatic compound is polycyclic with two or more rings, at least one ORf moiety may be attached to only one aromatic ring, or at least one ORf moiety may be attached to multiple aromatic rings.

[0185] The product obtained in step 4 (excluding the raw materials) contains 10 mol% or more of aromatic compounds having an ORf moiety, preferably 30 mol% or more, more preferably 40 mol% or more, even more preferably 50 mol% or more, and particularly preferably 60 mol% or more.

[0186] The product obtained in step 4 can be desoldered by appropriate methods, thereby obtaining a product containing an aromatic compound having an ORf moiety, for example, as a solid. The solid thus collected can be purified, dried, or otherwise processed by appropriate methods to obtain the target aromatic compound having an ORf moiety with high purity.

[0187] Examples of aromatic compounds having an ORf moiety obtained in step 4 include compounds (A1) to (A24) represented by the following structural formulas. In the formulas, Me represents a methyl group.

[0188] [ka]

[0189] [ka]

[0190] The method for producing a fluoroether compound according to this disclosure may consist only of step 4, or it may include other steps besides step 4.

[0191] The method for producing fluoroether compounds, including step 4, allows for the synthesis of fluoroether compounds by a simple method. The resulting fluoroether compounds can be used, for example, as pharmaceutical compounds and can be widely applied to various other uses.

[0192] 6. Method for producing fluoroether compounds 3 Another embodiment of the fluoroether compound production method 1 of this disclosure is the fluoroether compound production method 3, which comprises a step of obtaining a fluoroether compound using an N-fluoroalkoxy compound having a fluoroalkoxy group on the nitrogen of a nitrogen-containing heterocyclic compound (hereinafter, this step will be referred to as "step 5").

[0193] In step 5, an N-fluoroalkoxy compound having a fluoroalkoxy group on the nitrogen of a nitrogen-containing heterocyclic compound is reacted with an aromatic compound. More specifically, an N-fluoroalkoxy compound having a fluoroalkoxy group on the nitrogen of an imidazole compound is reacted with an aromatic compound. More specifically, an N-fluoroalkoxy compound having a fluoroalkoxy group on the nitrogen of a benzimidazole compound is reacted with an aromatic compound.

[0194] In step 5, it is preferable to react the N-fluoroalkoxy compound represented by formula (3'd), described below, with the aromatic compound. This allows us to obtain an aromatic compound having an ORf moiety. Here, Rf is synonymous with Rf in formula (3'd). Therefore, the product obtained in step 5 has a structure in which the ORf moiety is bonded to the aromatic compound.

[0195] In other words, an example of the method 3 for producing a fluoroether compound according to this disclosure is a method for producing a fluoroether compound comprising step 5 of obtaining a fluoroether compound using an N-fluoroalkoxy compound represented by the following formula (3'd).

[0196] [ka]

[0197] In formula (3'd), Rf represents a fluoroalkyl group having 2 carbon atoms, and R 9 , R 10 , R 11 , R 12 , R 14 , R 15 , R 16 , R 17 , and, R 18 Each of these represents either the same or different hydrogen atoms or a monovalent group.

[0198] In formula (3´d), R 9 , R 10 , R 11 , R 12 , R 14 , R 15 , R 16 , R 17 , and, R 18 R in equation (3d) 9 , R 10 , R 11 , R 12 , R 14 , R 15 , R 16 , R 17 , and, R 18 These are synonymous. For example, an N-fluoroalkoxy compound represented by formula (3'd) and R 9 No. 2, R 11 , R 15 and R 17 CF3, R 10 , R 12 , R 14 , R 16 , and R 18 Examples of compounds in which hydrogen is present are given.

[0199] In step 5, the same conditions as in step 4 can be adopted, except that the N-fluoroalkoxy compound represented by formula (3'd) is used. Therefore, the aromatic compound used in step 5 can be the same compound as the aromatic compound used in step 4, and the reaction conditions are the same as those in step 4. In other words, in step 4, the N-fluoroalkoxy compound represented by formula (3'd) can be used instead of the benzotriazole salt represented by formula (3'c).

[0200] In specifying the inventions contained herein, the components (properties, structures, functions, etc.) described in each embodiment of this disclosure may be combined in any way. That is, this disclosure encompasses all subject matter consisting of any combination of the combinatable components described herein. [Examples]

[0201] The present invention will be described more specifically below with reference to examples, but the present invention is not limited to the embodiments of these examples.

[0202] (Example 1a) CF3SO2Na (sodium trifluoromethanesulfinate) and N-hydroxyphthalimide (in formula (2a-2), R 5 , R 6 , R 7 , and, R 8 A compound in which R is hydrogen, ammonium hexanitratocerium(IV)ate (hereinafter abbreviated as CAN) as an inorganic oxidizing agent, and a mixed solvent of acetonitrile and water (acetonitrile:water = 4:1, v / v) as a solvent were charged into the reactor. The reaction was carried out by stirring the reactor for 1 hour while maintaining the reactor at room temperature (25°C) (Step 1). In this reaction, the molar ratio of CF3SO2Na to N-hydroxyphthalimide (CF3SO2Na:N-hydroxyphthalimide) was 1:1, 2 equivalents of the inorganic oxidizing agent were used, and the concentration of CF3SO2Na in the solvent was 0.2M. As a result of the reaction in Step 1, an N-fluoroalkoxy compound (in formula (3b), R 5 , R 6 , R7 , and, R 8 A compound in which Rf is hydrogen and Rf is CF3 was obtained in a yield of 45%. 1 1H NMR and 19 The results of the 1F NMR were as follows: 1 H NMR (300 MHz, CDCl3) δ 7.97-7.95 (m,2H),7.88-7.86. 19 F NMR (282 MHz, CDCl3) δ -65.7 (s 3F).

[0203] (Example 1b) The reaction in step 1 was carried out in the same manner as in Example 1a, except that the solvent was changed to acetone, and the N-fluoroalkoxy compound was obtained in a yield of 53%.

[0204] (Example 1c) The reaction in step 1 was carried out in the same manner as in Example 1b, except that the concentration of CF3SO2Na in the solvent was changed to 0.4 M, and the N-fluoroalkoxy compound was obtained in a yield of 50%.

[0205] (Example 1d) The reaction in step 1 was carried out in the same manner as in Example 1b, except that the concentration of CF3SO2Na in the solvent was changed to 0.1 M, and the N-fluoroalkoxy compound was obtained in a yield of 53%.

[0206] (Example 1e) The reaction in step 1 was carried out in the same manner as in Example 1b, except that the concentration of CF3SO2Na in the solvent was changed to 0.05 M, and the N-fluoroalkoxy compound was obtained in a yield of 53%.

[0207] (Example 1f) The reaction in step 1 was carried out in the same manner as in Example 1b, except that the molar ratio of CF3SO2Na to N-hydroxyphthalimide was changed to 1:1.5 and the amount of inorganic oxidizing agent used was changed to 2.5 equivalents, and an N-fluoroalkoxy compound was obtained in a yield of 58%.

[0208] (Example 1g) The reaction in step 1 was carried out in the same manner as in Example 1b, except that the molar ratio of CF3SO2Na to N-hydroxyphthalimide was changed to 1:2 and the amount of inorganic oxidizing agent used was changed to 3 equivalents, and an N-fluoroalkoxy compound was obtained in a yield of 73%.

[0209] (Example 2a) C2F5SO2Na and N-hydroxyphthalimide (in formula (2a-2), R 5 , R 6 , R 7 , and, R 8 A compound in which R is hydrogen, ammonium hexanitratocerium(IV)ate (hereinafter abbreviated as CAN) as an inorganic oxidizing agent, and a mixed solvent of acetonitrile and water (acetonitrile:water = 4:1, v / v) as a solvent were charged into the reactor. The reaction was carried out by stirring the reactor for 5 minutes while maintaining the reactor at room temperature (25°C) (Step 1). In this reaction, the molar ratio of C2F5SO2Na to N-hydroxyphthalimide (C2F5SO2Na:N-hydroxyphthalimide) was 1:1.5, 4 equivalents of the inorganic oxidizing agent were used, and the concentration of the starting materials (C2F5SO2Na and N-hydroxyphthalimide) relative to the solvent was 0.05 M. As a result of the reaction in Step 1, an N-fluoroalkoxy compound (in formula (3b), R 5 , R 6 , R 7 , and, R 8 A compound in which Rf is hydrogen and Rf is C2F5 was obtained in 80% yield.

[0210] (Example 2b) The reaction in step 1 was carried out in the same manner as in Example 2a, except that C2F5SO2Na was replaced with C3F7SO2Na, and an N-fluoroalkoxy compound was obtained in a yield of 76%.

[0211] (Example 2c) The reaction in step 1 was carried out in the same manner as in Example 2a, except that C2F5SO2Na was replaced with C4F9SO2Na, and an N-fluoroalkoxy compound was obtained in a yield of 60%.

[0212] (Example 2d) C2F5SO2Na to C5F 11 The reaction in step 1 was carried out in the same manner as in Example 2a, except that SO2Na was used instead, and the N-fluoroalkoxy compound was obtained in a yield of 59%.

[0213] (Example 2e) C2F5SO2Na to C6F 13 The reaction in step 1 was carried out in the same manner as in Example 2a, except that SO2Na was used instead, and an N-fluoroalkoxy compound was obtained in a yield of 66%.

[0214] (Example 2f) C2F5SO2Na to C 10 The reaction in step 1 was carried out in the same manner as in Example 2a, except that F21SO2Na was used, and an N-fluoroalkoxy compound was obtained in a yield of 42%.

[0215] (Example 3a) CF3SO2Na and a 1-hydroxybenzotriazole derivative (in formula (2a-3), R 9 No. 2, R 10 is hydrogen, R 11 CF3, R 12 A compound in which R is hydrogen, ammonium hexanitratocerium(IV)ate (hereinafter abbreviated as CAN) as an inorganic oxidizing agent, and a mixed solvent of acetonitrile and water (acetonitrile:water = 4:1, v / v) as a solvent were charged into the reactor. The reaction was carried out by stirring the reactor for 5 minutes while maintaining the reactor at room temperature (25°C) (Step 1). In this reaction, the molar ratio of CF3SO2Na to 1-hydroxybenzotriazole derivative (CF3SO2Na:1-hydroxybenzotriazole derivative) was 1:1.5, 4 equivalents of the inorganic oxidizing agent were used, and the concentration of the starting materials (CF3SO2Na and 1-hydroxybenzotriazole derivative) relative to the solvent was 0.05 M. As a result of the reaction in Step 1, the benzotriazole derivative (in formula (3c), R 9 No. 2, R 10 is hydrogen, R 11 CF3, R 12 A compound in which Rf is hydrogen and Rf is CF3 was obtained in 70% yield.1 1H NMR and 19 The results of the 1F NMR were as follows: 1 H NMR (300 MHz, CDCl3) δ 8.61 (s,1H),8.31 (s,1H). 19 F NMR (282 MHz, CDCl3) δ -62.6 (s,3F),-64.7 (s,3F).

[0216] (Example 3b) The reaction in step 1 was carried out in the same manner as in Example 3a, except that CF3SO2Na was replaced with C2F5SO2Na, and a benzotriazole derivative was obtained in a yield of 57%.

[0217] (Example 3c) The reaction in step 1 was carried out in the same manner as in Example 3a, except that CF3SO2Na was replaced with C3F7SO2Na, and a benzotriazole derivative was obtained in a yield of 44%.

[0218] (Example 3d) The reaction in step 1 was carried out in the same manner as in Example 3a, except that CF3SO2Na was replaced with C4F9SO2Na, and a benzotriazole derivative was obtained in a yield of 46%.

[0219] (Example 3e) CF3SO2Na to C5F 11 The reaction in step 1 was carried out in the same manner as in Example 3a, except that SO2Na was used instead, and a benzotriazole derivative was obtained in a yield of 45%.

[0220] (Example 3f) CF3SO2Na to C6F 13 The reaction in step 1 was carried out in the same manner as in Example 3a, except that SO2Na was used instead, and a benzotriazole derivative was obtained in a yield of 61%.

[0221] (Example: 3g) The reaction in step 1 was carried out in the same manner as in Example 3a, except that CF3SO2Na was replaced with CF2ClCFClCF2CF2SO2Na, and a benzotriazole derivative was obtained in a yield of 76%.

[0222] (Example 4a) CF3SO2Na and N-hydroxyphthalimide (in formula (2a-2), R 5 , R 6 , R 7 , and, R 8 A compound in which R is hydrogen, ammonium hexanitratocerium(IV)ate (hereinafter abbreviated as CAN) as an inorganic oxidizing agent, and acetone as a solvent were charged into the reactor. The reaction was carried out by stirring the reactor for 1 hour while maintaining the reactor at room temperature (25°C) (Step 1). In this reaction, the molar ratio of CF3SO2Na to N-hydroxyphthalimide (CF3SO2Na:N-hydroxyphthalimide) was 1:2, 3 equivalents of the inorganic oxidizing agent were used, and the concentration of the starting materials (CF3SO2Na and N-hydroxyphthalimide) relative to the solvent was 0.2M. As a result of the reaction in Step 1, an N-fluoroalkoxy compound (in formula (3b), R 5 , R 6 , R 7 , and, R 8 A compound in which Rf is hydrogen and Rf is CF3 was obtained in a yield of 74%.

[0223] (Example 4b) The reaction in step 1 was carried out in the same manner as in Example 4a, except that CF3SO2Na was replaced with C2F5SO2Na, and a benzotriazole derivative was obtained in a yield of 76%.

[0224] (Example 4c) The reaction in step 1 was carried out in the same manner as in Example 4a, except that CF3SO2Na was replaced with C3F7SO2Na, and a benzotriazole derivative was obtained in a yield of 84%.

[0225] (Example 4d) The reaction in step 1 was carried out in the same manner as in Example 4a, except that CF3SO2Na was replaced with C4F9SO2Na, and a benzotriazole derivative was obtained in a yield of 74%.

[0226] (Example 4e) CF3SO2Na to C5F 11 The reaction in step 1 was carried out in the same manner as in Example 4a, except that SO2Na was used instead, and a benzotriazole derivative was obtained in a yield of 55%.

[0227] (Example 4f) CF3SO2Na to C6F 13 The reaction in step 1 was carried out in the same manner as in Example 4a, except that SO2Na was used instead, and a benzotriazole derivative was obtained in a yield of 69%.

[0228] (Example: 4g) The reaction in step 1 was carried out in the same manner as in Example 4a, except that CF3SO2Na was replaced with CF2ClCFClCF2CF2SO2Na, and a benzotriazole derivative was obtained in a yield of 88%.

[0229] (Example 5a) CF3SO2Na and N-hydroxysuccinimide (in formula (2a-1), R 1 , R 2 , R 3 , and, R 4 A compound in which R is hydrogen, ammonium hexanitratocerium(IV)ate (hereinafter abbreviated as CAN) as an inorganic oxidizing agent, and acetone as a solvent were charged into the reactor. The reaction was carried out by stirring the reactor for 1 hour while maintaining the reactor at room temperature (25°C) (Step 1). In this reaction, the molar ratio of CF3SO2Na to N-hydroxysuccinimide (CF3SO2Na:N-hydroxysuccinimide) was 1:2, 3 equivalents of the inorganic oxidizing agent were used, and the concentration of CF3SO2Na in the solvent was 0.2M. As a result of the reaction in Step 1, N-hydroxysuccinimide (in formula (3a), R 1 , R 2 , R 3 , and, R 4A compound in which Rf is hydrogen and Rf is CF3 was obtained in a yield of 43%.

[0230] (Example 5b) The reaction in step 1 was carried out in the same manner as in Example 5a, except that CF3SO2Na was replaced with C2F5SO2Na, and an N-hydroxysuccinimide derivative was obtained in a yield of 49%.

[0231] (Example 5c) The reaction in step 1 was carried out in the same manner as in Example 5a, except that CF3SO2Na was replaced with C3F7SO2Na, and an N-hydroxysuccinimide derivative was obtained in a yield of 46%.

[0232] (Example 5d) Under a nitrogen atmosphere, 156 mg of CF3SO2Na, 459 mg of N-hydroxy-2-(3,5-bistrifluoromethylphenyl)-4-nitro-6-trifluoromethyl-benzimidazole, and 8.0 mL of acetonitrile were added to a 20 mL glass container. 2.0 mL of 2.0 mol / L aqueous solution of cerium(IV) ammonium nitrate was added to the container, and the mixture was stirred at room temperature for 10 minutes. Water was added to the resulting reaction mixture, and it was extracted with diethyl ether. The diethyl ether was removed by distillation, and the resulting crude product was purified by column chromatography to obtain a purified product with an isolation yield of 65%. 1 1H NMR and 19 The results of the 1F NMR were as follows: 1 H NMR (300 MHz, CDCl3) δ 8.65 (s,2H),8.52 (s,1H),8.16 (s,1H),8.14 (s,1H). 19 F NMR (282 MHz, CDCl3) δ -62.0 (s,3F),-63.6(s,6F),-64.0 (s,3F)

[0233] (Example 5e) The reaction was carried out in the same manner as in Example 5d, except that CF3SO2Na was replaced with C2F5SO2Na, and a purified product was obtained with an isolation yield of 65%.

[0234] (Example 5f) CF3SO2Na to C6F 13 The reaction was carried out in the same manner as in Example 5d, except that SO2Na was used, and a purified product was obtained with an isolation yield of 63%.

[0235] (Example: 5g) The reaction was carried out in the same manner as in Example 5d, except that CF3SO2Na was replaced with CF2ClCFClCF2CF2SO2Na, and a purified product was obtained with an isolation yield of 77%.

[0236] (Example 6a) N-fluoroalkoxy compounds (in formula (3b), R 5 , R 6 , R 7 , and, R 8 Step 2 involved reacting a compound (where Rf is hydrogen and Rf is C2F5) with PhCOO(CH2)4-X (where Ph is a phenyl group (C6H5-) and X is I) in N,N-dimethylacetamide in the presence of tetrabutylammonium iodide at 80°C for 16 hours. In this reaction, the molar ratio of PhCOO(CH2)4-X to the N-fluoroalkoxy compound (PhCOO(CH2)4-X:N-fluoroalkoxy compound) was 1:2.5, and 1 equivalent of tetrabutylammonium iodide was used. The reaction in Step 2 yielded PhCOO(CH2)4-OC2F5 in 61% yield.

[0237] (Example 6b) The reaction in step 2 was carried out in the same manner as in Example 6a, except that X was changed to PhCOO(CH2)4-X, which is Br, and PhCOO(CH2)4-OC2F5 was obtained in a yield of 66%.

[0238] (Example 6c) The reaction in step 2 was carried out in the same manner as in Example 6a, except that X was changed to PhCOO(CH2)4-X, which is an OM, and PhCOO(CH2)4-OC2F5 was obtained in a yield of 66%.

[0239] (Example 6d) The reaction in step 2 was carried out in the same manner as in Example 6a, except for various changes to PhCOO(CH2)4-X(X=I), and the products (a), (b), (c), (d), (e), (f), (g), (h), and (i) shown in Figure 1 were obtained in the yields shown in Figure 1 (in Figure 1, the numbers to the right of the product are the yields).

[0240] (Example 6e) The reaction in step 2 was carried out in the same manner as in Example 6b, except for various changes to PhCOO(CH2)4-X(X=Br), and the products (j) and (k) shown in Figure 2 were obtained in the yields shown in Figure 2 (in Figure 2, the numbers to the right of the product indicate the yield).

[0241] (Example 6f) The reaction in step 2 was carried out in the same manner as in Example 6a, except that Rf was changed to an N-fluoroalkoxy compound with C3F7, and PhCOO(CH2)4-OC3F7 was obtained in a yield of 48%. 1 1H NMR and 19 The results of the 1F NMR were as follows: 1 H NMR (300 MHz, CDCl3) δ 8.05-8.03 (m,2H), 7.59-7.55 (m,1H),7.47-7.43 (m,2H),4.38-4.34 (m,2H),4.14-4.11 (m,2H),1.93-1.88 (m,4H). 19 F NMR (282 MHz, CDCl3) δ -81.9 (s,3F),-87.2 (s,2F),-129.9 (s,2F).

[0242] (Example: 6g) Rf is C6F 13 The reaction in step 2 was carried out in the same manner as in Example 6a, except that the N-fluoroalkoxy compound was changed to PhCOO(CH2)4-OC6F 13 This was obtained with a yield of 60%. 1 1H NMR and 19 The results of the 1F NMR were as follows: 1H NMR (300 MHz, CDCl3) δ 8.05-8.03 (m,2H), 7.59-7.55 (m,1H),7.46-7.43 (m,2H),4.38-4.36 (m,2H),4.14-4.12 (m,2H),1.90-1.88 (m,4H). 19 F NMR (282 MHz, CDCl3) δ -81.2 (s,3F),-85.7 (s,2F),-122.8 (s,2F),-122.3 (s,2F),-125.7 (s,2F),-126.6 (s,2F).

[0243] (Example 6h) N-fluoroalkoxy compounds (in formula (3b), R 5 , R 6 , R 7 , and, R 8 Rf is hydrogen, Rf is C6F 13 After storing the compound (which is ) under a nitrogen atmosphere, the N-fluoroalkoxy compound and CH3O-PhCOO(CH2)3-X (where Ph is a phenyl group (C6H5-), X is I, and CH3O is bonded at the para position) were reacted in N,N-dimethylacetamide in the presence of tetrabutylammonium iodide at 80°C for 16 hours (Step 2). In this reaction, the molar ratio of CH3O-PhCOO(CH2)3-X to the N-fluoroalkoxy compound (CH3O-PhCOO(CH2)3-X:N-fluoroalkoxy compound) was 1:2.5, and 1 equivalent of tetrabutylammonium iodide was used. As a result of the reaction in Step 2, CH3O-PhCOO(CH2)3-OC6F 13 This was obtained in a yield of 95%.

[0244] (Example 6i) CH3O-PhCOO(CH2)3-OC6F was prepared in the same manner as in Example 6h, except that the N-fluoroalkoxy compound was stored in air for 24 hours instead of under a nitrogen atmosphere. 13The product was obtained in a yield of 91%. This result showed that the yield was equivalent to that of Example 6h, indicating that the target product can be synthesized in high yield even when using N-fluoroalkoxy compounds stored in air. In other words, N-fluoroalkoxy compounds can be used without requiring strict storage control.

[0245] (Example 6') N-fluoroalkoxy compounds (in formula (3c-1), R 9 No. 2, R 10 is hydrogen, R 11 CF3, R 12 A compound in which R is hydrogen and Rf is a fluoroethyl group was reacted with methyl trifluoromethanesulfonate as an alkylating agent (methylating agent) in n-hexane at 50°C for 48 hours (Step 3). In this reaction, the molar ratio of the N-fluoroalkoxy compound to the alkylating agent (N-fluoroalkoxy compound:alkylating agent) was 1:3, and the concentration of the starting materials (N-fluoroalkoxy compound and alkylating agent) relative to the solvent was 0.5 M. As a result of the reaction in Step 3, a benzotriazole salt (in formula (3'c), R 9 No. 2, R 10 is hydrogen, R 11 CF3, R 12 is hydrogen, R 13 A compound in which Rf is a methyl group, Rf is a fluoroethyl group, and X is an OTf group was obtained in 89% yield. 1 1H NMR and 19 The results of the 1F NMR were as follows: 1 H NMR (300 MHz, CD3CN) δ 9.06 (s,1F),9.02 (s,1F),4.92 (s,3F). 19 F NMR (282 MHz, CD3CN) δ -60.9 (s,3F),-77.2 (s,3F),-80.8 (t, J = 2.0 Hz, 3F),-87.7 (d, J = 2.0 Hz, 2F).

[0246] (Example 7a) Step 4 involved adding the benzotriazole salt obtained in Example 6', benzene as an aromatic compound, and tris(2,2'-bipyridine)ruthenium(II)bis(hexafluorophosphate) (Ru(bpy)3(PF6)2) to acetonitrile to obtain a starting material solution, which was then irradiated with an active energy beam at room temperature (25°C) for 1 hour. In this reaction, the molar ratio of benzotriazole salt to benzene (benzotriazole salt:benzene) was 1:10, Ru(bpy)3(PF6)2 was used in an amount of 1 mol% relative to the benzotriazole salt, the active energy beam was a blue LED (45W), and the concentration of the starting materials (benzotriazole salt and aromatic compound) relative to the solvent was 0.2 M. The reaction in Step 4 yielded Ph-OC2F5 (Ph being a phenyl group) in 83% yield. 19 The results of the 1F NMR were as follows: 19 F NMR (282 MHz, CDCl3) δ 85.8 (s,3F),-87.2 (s,2F).

[0247] (Example 7b) The reaction in step 4 was carried out in the same manner as in Example 7a, except that the molar ratio of benzotriazole salt to benzene (benzotriazole salt:benzene) was changed to 1:5, and Ph-OC2F5 was obtained in a yield of 62%.

[0248] (Example 7c) In the reaction of step 4, Ru(bpy)3(PF6)2 was used in an amount of 5 mol% relative to the benzotriazole salt, and the concentration of the starting material relative to the solvent was 0.1 M. The reaction of step 4 was carried out in the same manner as in Example 7a, and Ph-OC2F5 was obtained in a yield of 73%.

[0249] (Example 7d) The reaction in step 4 was carried out in the same manner as in Example 7a, except that nitromethane was used instead of acetonitrile, and Ph-OC2F5 was obtained in a yield of 69%.

[0250] (Example 7e) The reaction in step 4 was carried out in the same manner as in Example 7a, except that acetone was used instead of acetonitrile, and Ph-OC2F5 was obtained in a yield of 68%.

[0251] (Example 7f) The reaction in step 4 was carried out in the same manner as in Example 7a, except that ethyl acetate was used instead of acetonitrile, and Ph-OC2F5 was obtained in a yield of 58%.

[0252] (Example: 7g) The reaction in step 4 was carried out in the same manner as in Example 7a, except that hexafluoro-2-propanol was used instead of acetonitrile, and Ph-OC2F5 was obtained in a yield of 46%.

[0253] (Example 7h) The reaction in step 4 was carried out in the same manner as in Example 7a, except that benzene was used instead of acetonitrile, and Ph-OC2F5 was obtained in a yield of 65%.

[0254] (Example 7i) The reaction in step 4 was carried out in the same manner as in Example 7a, except that a 1:1 mixed solvent of acetonitrile-1,2-dichloroethane was used instead of acetonitrile in step 4, and Ph-OC2F5 was obtained in a yield of 72%.

[0255] (Example 7j) The reaction in step 4 was carried out in the same manner as in Example 7c, except that Ru(bpy)3(PF6)2 was used in an amount of 2 mol% relative to the benzotriazole salt, and Ph-OC2F5 was obtained in a yield of 77%.

[0256] (Example 7k) The reaction in step 4 was carried out in the same manner as in Example 7c, except that Ru(bpy)3(PF6)2 was used in an amount of 1 mol% relative to the benzotriazole salt, and Ph-OC2F5 was obtained in a yield of 78%.

[0257] (Example 7m) The reaction in step 4 was carried out in the same manner as in Example 7c, except that Ru(bpy)3(PF6)2 was used in an amount of 0.5 mol% relative to the benzotriazole salt, and Ph-OC2F5 was obtained in a yield of 72%.

[0258] (Example 8a) The reaction in step 4 was carried out in the same manner as in Example 7a, except that the aromatic compound was changed to toluene, and CH3-C6H4-OC2F5 was obtained in a yield of 55% (a mixture of ortho, meta, and para isomers).

[0259] (Example 8b) The reaction in step 4 was carried out in the same manner as in Example 7a, except that the aromatic compound was changed to bromobenzene, and Br-C6H4-OC2F5 was obtained in a yield of 55% (ortho:meta:para = 1:3.7:4.3).

[0260] (Example 8c) The reaction in step 4 was carried out in the same manner as in Example 7a, except that the aromatic compound was changed to CH3CO-Ph, to obtain CH3CO-C6H4-OC2F5 (a mixture of ortho, meta, and para isomers).

[0261] (Example 8d) The reaction in step 4 was carried out in the same manner as in Example 7a, except that the aromatic compound was changed to paradichlorobenzene, to obtain Cl-C6H3Cl(OC2F5) (a mixture of ortho, meta, and para isomers).

[0262] (Example 8e) The reaction in step 4 was carried out in the same manner as in Example 7a, except that the aromatic compound was changed to CH3CO-C6H4-OCF3(p-isomer), to obtain CH3CO-C6H3(OCF3)(OC2F5) (a mixture of ortho, meta, and para isomers).

[0263] (Example 9a) The reaction in step 4 was carried out in the same manner as in Example 7a, except that the activation energy ray was changed to 6 hours at room temperature (25°C), and Ph-OC2F5 was obtained in a yield of 74%.

[0264] (Example 9b) The reaction in step 4 was carried out in the same manner as in Example 9a, except that the aromatic compound was changed to CH3OCO-C6H4-F(p-isomer), and CH3OCO-C6H3(F)(OC2F5) was obtained in a yield of 52% (a mixture of ortho, meta, and para isomers).

[0265] (Example 9c) The reaction in step 4 was carried out in the same manner as in Example 9a, except that the aromatic compound was changed to CH3OCO-C6H4-Cl(p-isomer), and CH3OCO-C6H3(Cl)(OC2F5) was obtained in 70% yield (a mixture of ortho, meta, and para isomers).

[0266] (Example 9d) The reaction in step 4 was carried out in the same manner as in Example 9a, except that the aromatic compound was changed to CH3OCO-C6H4-Br(p-isomer), and CH3OCO-C6H3(Br)(OC2F5) was obtained in 70% yield (a mixture of ortho, meta, and para isomers).

[0267] (Example 9e) The reaction in step 4 was carried out in the same manner as in Example 9a, except that the aromatic compound was changed to CH3CO-C6H4-Cl(p-isomer), and CH3CO-C6H3(Cl)(OC2F5) was obtained in a yield of 59% (a mixture of ortho, meta, and para isomers).

[0268] (Example 9f) The reaction in step 4 was carried out in the same manner as in Example 9a, except that the aromatic compound was changed to NO2-C6H4-Cl(p-isomer), and NO2-C6H3(Cl)(OC2F5) was obtained in a yield of 48% (a mixture of ortho, meta, and para isomers).

[0269] (Example: 9g) The reaction in step 4 was carried out in the same manner as in Example 9a, except that the aromatic compound was changed to CH3OCOC6H2-Cl3, and the compound represented by the following formula (9g) was obtained in a yield of 67%.

[0270] (Examples 9h, 9i, 9j, and 9k) The reaction in step 4 was carried out in the same manner as in Example 9a, except that the aromatic compound was changed in various ways, to obtain the corresponding compound. In Example 9h, the compound represented by formula (9h) was obtained in a yield of 75%, in Example 9i, the compound represented by formula (9i) was obtained in a yield of 65%, in Example 9j, the compound represented by formula (9j) was obtained in a yield of 51%, and in Example 9k, the compound represented by formula (9k) was obtained in a yield of 54%.

[0271] [ka]

[0272] (Example 10a) The reaction in step 4 was carried out in the same manner as in Example 7a, except that the activation energy ray was changed to 2 hours at room temperature (25°C) and the aromatic compound was changed to biphenyl, and the compound represented by formula (10a) was obtained in a yield of 37%.

[0273] (Example 10b) The reaction in step 4 was carried out in the same manner as in Example 7a, except that the activation energy ray was changed to 2 hours at room temperature (25°C), the aromatic compound was changed to biphenyl, the molar ratio of benzotriazole salt to biphenyl (benzotriazole salt:biphenyl) was changed to 2:1, and the concentration of the starting materials (benzotriazole salt and aromatic compound) relative to the solvent was changed to 1 M, and the compound represented by formula (10b) was obtained in a yield of 35%.

[0274] [ka]

[0275] (Example 11a) Synthesis of perfluoroethylphenyl ether using N-perfluoroethoxy-2-allyl-benzimidazole The reaction was carried out according to the scheme shown in formula (11a) below (step 5). Specifically, under a nitrogen atmosphere, 115.4 mg of N-perfluoroethoxy-2-allyl-benzimidazole, 0.0516 mg of tri(2,2'-bipyridine)ruthenium(II)bis(hexafluorophosphate), 0.178 mL of benzene, and 1.0 mL of acetonitrile were added to a 15 mL glass container. The container was stirred at room temperature for 1 hour under blue LED light irradiation. The resulting reaction mixture 19 Analysis using 1F NMR revealed that the perfluoroethylphenyl ether mentioned in the title was produced in a yield of 43%.

[0276] [ka]

Claims

1. In the presence of an inorganic oxidizing agent, N-hydroxy compounds and, The following general formula (1) RfSO ２ M (1) (In formula (1), Rf is a fluoroalkyl group having one or more carbon atoms, and M is an alkali metal or alkaline earth metal.) Sulfinic acid compounds represented by The process includes a step of obtaining an N-fluoroalkoxy compound through a reaction with, The aforementioned N-hydroxy compound is The following general formula (2a) 【Chemistry 1】 (In formula (2a), R １ａ This refers to a group containing a carbonyl group or a group containing an aryl group which may have a substituent. R ２ａ This indicates a group containing a carbonyl group, a group containing an -N=N bond, or a group containing an -N=C- bond. R １ａ and R ２ａ These may bond with each other along with the nitrogen atom to which they are bonded, forming a saturated or unsaturated ring. The saturated or unsaturated ring may have an aromatic ring, which may have substituents, further bonded to it. Compounds represented by, The following general formula (2b) 【Chemistry 2】 (In formula (2b), R ３ａ (This indicates an aryl group which may have a substituent.) Compounds represented by, One or more species selected from the group consisting of, The N-fluoroalkoxy compound is a compound having an N-O-Rf moiety. A method for producing N-fluoroalkoxy compounds.

2. The manufacturing method according to claim 1, wherein the inorganic oxidizing agent is in a solid state under atmospheric pressure and in an atmosphere of 25°C.

3. The manufacturing method according to claim 1, wherein the inorganic oxidizing agent is a compound containing a metal.

4. The method for producing the inorganic oxidizing agent according to claim 3, wherein the inorganic oxidizing agent is a compound containing cerium.

5. The method for producing the product according to claim 4, wherein the inorganic oxidizing agent is ammonium hexanitratocerium(IV)ate.

6. The manufacturing method according to claim 1, wherein the reaction is carried out in the presence of a solvent.

7. The aforementioned N-hydroxy compound is N-hydroxysuccinimide or its derivatives, N-hydroxyphthalimide or its derivatives, 1-hydroxybenzotriazole or its derivatives, and 1-Hydroxybenzoimidazole or its derivatives A manufacturing method according to any one of claims 1 to 6, wherein one or more are selected from the group consisting of the following.

8. The following general formula (3a) 【Transformation 3】 (In formula (3a), Rf represents a fluoroalkyl group having 1 or more carbon atoms, and R １ , R ２ , R ３ , and R ４ each independently represent hydrogen or a monovalent group.) An N-fluoroalkoxy compound represented by [the formula].

9. General formula (3b) below 【Chemistry 4】 (In equation (3b), Rf is -C(CF) ３ ) ２ It represents a fluoroalkyl group with 2 or more carbon atoms, excluding the F group, and R ５ , R ６ , R ７ , and, R ８ (Each of these represents the same or different hydrogen or monovalent group.) An N-fluoroalkoxy compound represented by [the formula].

10. The following general formula (3c) 【Transformation 5】 (In equation (3c), Rf is -C(CF) ３ ) ２ It represents a fluoroalkyl group with 2 or more carbon atoms, excluding the F group, and R ９ , R １０ , R １１ , and, R １２ (Each of these represents the same or different hydrogen or monovalent group.) An N-fluoroalkoxy compound represented by [the formula].

11. The following general formula (3d) 【Transformation 6】 (In equation (3d), Rf is -C(CF) ３ ) ２ It represents a fluoroalkyl group with 2 or more carbon atoms, excluding the F group, and R ９ , R １０ , R １１ , R １２ , R １４ , R １５ , R １６ , R １７ , and, R １８ (Each of these represents the same or different hydrogen or monovalent group.) An N-fluoroalkoxy compound represented by [the formula].

12. The following general formula (4a) 【Transformation 7】 (In equation (4a), Rf is -C(CF) ３ ) ２ It represents a fluoroalkyl group with 2 or more carbon atoms, excluding the F group, and R １ａ , R ２ａ R in formula (2a) １ａ , R ２ａ (This is synonymous with...) A compound represented by, The following general formula (4b) 【Transformation 8】 (In equation (4b), Rf is -C(CF) ３ ) ２ It represents a fluoroalkyl group with 2 or more carbon atoms, excluding the F group, and R ３ａ R in formula (2b) ３ａ (This is synonymous with...) A method for producing a fluoroether compound, comprising the step of obtaining a fluoroether compound using an N-fluoroalkoxy compound represented by [formula].

13. The following general formula (3c-1) 【Chemistry 9】 (In formula (3c-1), Rf represents a fluoroalkyl group having 2 carbon atoms, R ９ , R １０ , R １１ , and, R １２ N-fluoroalkoxy compounds represented by (where each is the same or different and represents hydrogen or a monovalent group), The following formula (4) R １３ ―X (4) (In formula (4), X represents a leaving group, R １３ (This indicates an alkyl group which may have substituents.) Alkylating agents represented by In response to this, The following general formula (3'c) 【Chemistry 10】 (In formula (3'c), Rf, R ９ , R １０ , R １１ , and, R １２ Rf, R in the above formula (3c-1) are ９ , R １０ , R １１ , and, R １２ This is synonymous with X and R １３ In equation (4), X and R １３ (This is synonymous with...) The process comprises obtaining a benzotriazole salt represented by A method for producing benzotriazole salts.

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