Monofluorosulfonylating agent composition, method for producing monofluorosulfonyloxy compound, and novel compound

Abstract

To provide a monofluorosulfonylating agent composition capable of monofluorosulfonylating a substrate containing a functional group such as a phenolic hydroxy group, and a method for producing a monofluorosulfonyloxy compound using the same.SOLUTION: The monofluorosulfonylating agent composition comprises a compound represented by general formula (1). Wherein X1, X2, Y1, and Y2 are N or CR, n is 1 to 3, and at least one R is an electron-withdrawing group represented by EWG. ] SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present disclosure relates to a monofluorosulfonylating agent composition capable of monofluorosulfonylating a substrate containing a functional group such as a phenolic hydroxyl group, a method for producing a monofluorosulfonyloxy compound using the same, and a novel compound. [Background technology]

[0002] The monofluorosulfonyl group (FSO2-) is a useful functional group that can be used in coupling reactions and covalent bond drugs. Monofluorosulfonylation of phenolic hydroxyl groups is an important reaction in pharmaceutical and material development. For example, Sharpless et al. reported the monofluorosulfonylation (FSO2) reaction of phenol using FSO2-imidazolium triflate salt (Non-Patent Document 1). The Shanghai Institute of Chemical Sciences, Chinese Academy of Chemical Sciences has filed a patent application for similar content (Patent Document 1). [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Special Publication No. 2021-504354 [Non-patent literature]

[0004] [Non-Patent Document 1] T. Guo, G. Meng, X. Zhan, Q. Yang, T. Ma, L. Xu, KBSharpless, J. Don, Angew. Chem. Int. Ed., 2018, 57, 2605-2610. Summary of the Invention [Problem to be solved by the invention]

[0005] However, the methods described in Patent Document 1 and Non-Patent Document 1 mentioned above have the following problems: in order to synthesize FSO2-imidazolium-triflate salt, a total of two reaction steps are required: a monofluorosulfonylation reaction of azoles and a reaction to convert to methyl triflate salt; and the second reaction step requires the use of methyl triflate (MeOTf), which emits smoke. Furthermore, there is still room for further study of monofluorosulfonylation reagents from the standpoint of economic efficiency and reduction of by-products.

[0006] The present disclosure has been made in view of these circumstances. An object of the present disclosure is to provide a monofluorosulfonylating agent composition that can be easily produced and that can monofluorosulfonylate a substrate having a functional group such as a phenolic hydroxyl group in good yield while suppressing the production of by-products. Another object of the present disclosure is to provide a method for producing a monofluorosulfonyloxy compound using the monofluorosulfonylating agent composition. [Means for solving the problem]

[0007] In view of the above problems, the present inventors have conducted extensive research and have found that a monofluorosulfonylating agent composition containing a monofluorosulfonylating agent in a free form that can be easily produced by a single-step reaction of monofluorosulfonylation of azoles according to the present disclosure can monofluorosulfonylate a substrate having a functional group such as a phenolic hydroxyl group in good yield while suppressing the production of by-products.

[0008] That is, the present disclosure provides the inventions described in [1]-[7] below.

[0009] [1] The compound includes a compound represented by the following general formula (1): Monofluorosulfonylating agent composition. [ka] In general formula (1), X1 is a nitrogen atom or C(R 1 ) and X 2 is a nitrogen atom or C(R 2 ) and Y 1 is a nitrogen atom or C(R 3 ) and Y 2 is a nitrogen atom or C(R 4 ) and R 1 ~R 4 are each independently a hydrogen atom or a monovalent or divalent substituent, R 1 ~R 4 two adjacent substituents are divalent substituents, and they may be bonded to each other to form a ring, and the ring may be formed by a monovalent substituent R 5 and n is an integer from 1 to 3, R 1 R when there are multiple 1 may be the same or different, and R 2 R when there are multiple 2 may be the same or different, and R 5 R when there are multiple 5 may be the same or different, R 1 ~R 5 At least one of the following is present as a monovalent substituent, and p of the monovalent substituents are electron-withdrawing groups represented by EWG, where p is an integer of 1 or more.

[0010] [2] The following general formula (2a): [ka] (In general formula (2a), X 11 is a nitrogen atom or C(R 11 ) and X 12 is a nitrogen atom or C(R 12 ) and Y 11 is a nitrogen atom or C(R 13 ) and Y 12 is a nitrogen atom or C(R 14) and R 11 ~R 14 are each independently a hydrogen atom or a monovalent substituent, R 11 ~R 14 at least one of the following is present as a monovalent substituent, and q of the monovalent substituents are electron-withdrawing groups represented by EWG, where q is an integer of 1 to 4; and / or a compound represented by the following general formula (2b): [ka] (In general formula (2b), X 21 is a nitrogen atom or C(R 21 ) and X 22 is a nitrogen atom or C(R 22 ) and X 23 is a nitrogen atom or C(R 23 ) and X 24 is a nitrogen atom or C(R 24 ) and Y 21 is a nitrogen atom or C(R 25 ) and Y 22 is a nitrogen atom or C(R 26 ) and R 21 ~R 26 are each independently a hydrogen atom or a monovalent or divalent substituent, R 21 ~R 26 two adjacent substituents are divalent substituents, and they may be bonded to each other to form a ring, and the ring may be formed by a monovalent substituent R 27 and R 27 R when there are multiple 27 may be the same or different, R 21 ~R 27 present as a monovalent substituent, and r of the monovalent substituents are electron-withdrawing groups represented by EWG, where r is an integer of 1 or more. Monofluorosulfonylating agent composition.

[0011] [3] In the general formula (2a), X 11 is C(R 11 ) and X 12 is C(R 12 ) and Y 11 is C(R 13 ) and Y 12 is a nitrogen atom, and R 11 , R 12 are each independently a hydrogen atom, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, or an electron-withdrawing group represented by EWG, and R 11 , R 12 At least one of the groups is an electron-withdrawing group represented by EWG, and R 13 is a hydrogen atom, a methyl group, an ethyl group, an n-propyl group, or an isopropyl group, In the general formula (2b), X 21 is C(R 21 ) and X 22 is C(R 22 ) and X 23 is C(R 23 ) and X 24 is C(R 24 ) and Y 21 is a nitrogen atom or C(R 25 ) and Y 22 is a nitrogen atom or C(R 26 ) and Y 21 , Y 22 At least one of R is a nitrogen atom, 22 , R 23 one of which is an electron-withdrawing group represented by EWG, and the other is a hydrogen atom, a methyl group, an ethyl group, an n-propyl group, or an isopropyl group; R 21 , R 24 , R 25 , R 26 are each independently a hydrogen atom, a methyl group, an ethyl group, an n-propyl group, or an isopropyl group.

[0012] [4] The monofluorosulfonylation agent composition according to any one of [1] to [3], wherein the electron-withdrawing group is a nitro group, a halogen atom, a cyano group, a carboxyl group, a trifluoromethyl group, an alkylcarbonyloxy group, a formyl group, an alkylcarbonyl group, or an alkoxycarbonyl group.

[0013] [5] The monofluorosulfonylating agent composition according to any one of [1] to [4], General formula (3): Ar-OH (3) (In general formula (3), Ar represents an aromatic ring group or a substituted aromatic ring group.) reacting with an aromatic hydroxyl compound represented by Method for producing monofluorosulfonyloxy compounds.

[0014] [6] The method for producing a monofluorosulfonyloxy compound according to [5], wherein the monofluorosulfonylating agent composition is reacted with the aromatic hydroxyl compound in the presence of a non-nucleophilic strong base.

[0015] [7] A compound represented by any one of the following general formulas (4a) to (4d): [ka] In general formula (4a), R represents an alkyl group having 1 to 8 carbon atoms. The NO2 group is bonded to a carbon atom on the ring to which R is not bonded. In general formula (4d), the NO2 group is bonded to a carbon atom on the six-membered ring to which no nitrogen atom is bonded. [Effects of the Invention]

[0016] According to the present disclosure, it is possible to provide a monofluorosulfonylating agent composition that can monofluorosulfonylate a substrate having a functional group such as a phenolic hydroxyl group in high yield while suppressing the production of by-products, using a free form that can be easily produced by a single-step reaction of monofluorosulfonylation of azoles alone. It is also possible to provide a method for producing a monofluorosulfonyloxy compound using the monofluorosulfonylating agent composition. Furthermore, it is possible to provide a novel compound corresponding to the free form. DETAILED DESCRIPTION OF THE INVENTION

[0017] In the present disclosure, the production of by-products is suppressed and the yield is excellent, and the reason for this is presumed to be as follows: In the present disclosure, by using a compound derived from an azole having an electron-withdrawing group as the monofluorosulfonylating agent composition, the azole is easily eliminated from the compound, making it easier to obtain the target monofluorosulfonyloxy compound.

[0018] The present disclosure will be described in detail below. Hereinafter, embodiments of the present disclosure will be described, but the present disclosure is not limited to the following embodiments and can be appropriately implemented based on the ordinary knowledge of those skilled in the art within the scope of the present disclosure.

[0019] <Monofluorosulfonylating agent composition> (Monofluorosulfonylating agent) The monofluorosulfonylating agent composition of the present disclosure (hereinafter also referred to as the composition of the present disclosure) contains a compound represented by the following general formula (1) as a monofluorosulfonylating agent.

[0020] [ka]

[0021] In general formula (1), X 1 is a nitrogen atom or C(R 1 ) and X 2 is a nitrogen atom or C(R 2) and Y 1 is a nitrogen atom or C(R 3 ) and Y 2 is a nitrogen atom or C(R 4 ) and R 1 ~R 4 are each independently a hydrogen atom or a monovalent or divalent substituent, R 1 ~R 4 two adjacent substituents are divalent substituents, and they may be bonded to each other to form a ring, and the ring may be formed by a monovalent substituent R 5 and n is an integer from 1 to 3, R 1 R when there are multiple 1 may be the same or different, and R 2 R when there are multiple 2 may be the same or different, and R 5 R when there are multiple 5 may be the same or different, R 1 ~R 5 At least one of the following is present as a monovalent substituent, and p of the monovalent substituents are electron-withdrawing groups represented by EWG, where p is an integer of 1 or more.

[0022] The electron-withdrawing group represented by EWG is a group that has the property of reducing the electron density of the imidazole moiety through the I effect (inductive effect). Preferred examples of the electron-withdrawing group represented by EWG include groups selected from a nitro group, a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom), a cyano group, a carboxyl group, a trifluoromethyl group, an alkylcarbonyloxy group, a formyl group, an alkylcarbonyl group, and an alkoxycarbonyl group. From the viewpoint of increasing the yield of the target product, the electron-withdrawing group is more preferably a group selected from a nitro group, a halogen atom, a cyano group, a carboxyl group, a trifluoromethyl group, and an alkoxycarbonyl group, even more preferably a group selected from a nitro group, a halogen atom, and a trifluoromethyl group, and particularly preferably a group selected from a nitro group and a halogen atom. A chlorine atom is preferred as the halogen atom. The number of carbon atoms in the alkyl group in the alkylcarbonyloxy group and alkylcarbonyl group is preferably 1 to 8, more preferably 1 to 3, and even more preferably 1. The number of carbon atoms in the alkoxy group in the alkoxycarbonyl group is preferably 1 to 8, more preferably 1 to 3, and even more preferably 1.

[0023] p represents the number of electron-withdrawing groups, represented by EWG, contained in the compound represented by general formula (1), and is an integer of 1 or greater. p is preferably an integer of 1 to 5, more preferably an integer of 1 to 3, and even more preferably 1 or 2. For example, R 1 , R 2 or each of R 5 It is particularly preferred that one of the groups is an electron withdrawing group.

[0024] In general formula (1), X 1 , X 2 , Y 1 , Y 2 Among these, usually 0 to 3 are nitrogen atoms, preferably 0 to 2 are nitrogen atoms, more preferably 1 or 2 are nitrogen atoms, and even more preferably 1 is a nitrogen atom. For example, X 1 is C(R 1 ) and X 2 is C(R 2 ) is preferable.1 , Y 2 Preferably, one or both of Y are nitrogen atoms. 1 is a nitrogen atom, and Y 2 is C(R 4 ) or Y 1 is C(R 3 ) and Y 2 is a nitrogen atom or Y 1 and Y 2 are preferably nitrogen atoms. 1 , Y 2 More preferably, one of the groups is a nitrogen atom.

[0025] R 1 ~R 4 The monovalent substituent in is preferably a linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, a branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, an aromatic heterocyclic group having 4 to 9 carbon atoms, or an electron-withdrawing group.

[0026] Examples of the linear aliphatic hydrocarbon group having 1 to 6 carbon atoms include a linear alkyl group having 1 to 6 carbon atoms, a linear alkenyl group having 2 to 6 carbon atoms, and a linear alkynyl group having 2 to 6 carbon atoms, and among these, a linear alkyl group having 1 to 6 carbon atoms is preferred. Examples of the linear alkyl group having 1 to 6 carbon atoms include a methyl group, an ethyl group, an n-propyl group, an n-butyl group, an n-pentyl group, and an n-hexyl group.

[0027] Examples of the branched aliphatic hydrocarbon group having 3 to 6 carbon atoms include a branched alkyl group having 3 to 6 carbon atoms, a branched alkenyl group having 3 to 6 carbon atoms, and a branched alkynyl group having 3 to 6 carbon atoms, and among these, a branched alkyl group having 3 to 6 carbon atoms is preferred. Examples of the branched alkyl group having 3 to 6 carbon atoms include an isopropyl group, an isobutyl group, a sec-butyl group, and a tert-butyl group.

[0028] Examples of the aromatic hydrocarbon group having 6 to 14 carbon atoms include a phenyl group, a benzyl group, a naphthyl group, and an anthryl group. Examples of the aromatic heterocyclic group having 4 to 9 carbon atoms include a pyrrole group, a pyrazine group, a pyrimidine group, and a pyridazine group.

[0029] R 1 ~R 4 The monovalent substituent in is preferably a linear alkyl group having 1 to 6 carbon atoms, a branched alkyl group having 3 to 6 carbon atoms, or an electron-withdrawing group, and more preferably a methyl group, an ethyl group, an n-propyl group, an isopropyl group, or an electron-withdrawing group.

[0030] R 1 ~R 4 Any two adjacent R groups may be divalent substituents, and these may be bonded to each other to form a ring. 1 ~R 4 The two adjacent ones of are R 1 and R 2 Two adjacent R 2 and R 4 Two adjacent R 3 and R 4 Two adjacent ones of R are listed. 1 ~R 4 The ring formed by bonding two adjacent rings is not particularly limited, but examples thereof include aromatic hydrocarbon rings having 6 to 14 carbon atoms (e.g., benzene ring, naphthalene ring, anthracene ring) and aromatic heterocyclic rings having 4 to 9 carbon atoms (e.g., pyrrole ring, pyrazine ring, pyrimidine ring, pyridazine ring). 5 The number of carbon atoms of the substituent is not included in the number of carbon atoms of the ring.

[0031] R 5 is preferably a linear alkyl group having 1 to 6 carbon atoms, a branched alkyl group having 3 to 6 carbon atoms, or an electron-withdrawing group.

[0032] The linear alkyl group having 1 to 6 carbon atoms and the branched alkyl group having 3 to 6 carbon atoms are, respectively, R 1 ~R4 Examples of the monovalent substituent in the formula (I) include a linear alkyl group having 1 to 6 carbon atoms and a branched alkyl group having 3 to 6 carbon atoms.

[0033] R 5 is preferably a methyl group, an ethyl group, an n-propyl group, an isopropyl group, or an electron-withdrawing group.

[0034] For example, R 1 and R 2 It is preferable that two adjacent R 1 and R 2 The ring formed by bonding two adjacent groups is not particularly limited, but may be, for example, a ring formed by bonding two adjacent groups 5 and the substituent R 5 More preferably, the substituent R is an aromatic hydrocarbon ring having 6 to 10 carbon atoms (for example, a benzene ring or a naphthalene ring) which may have 5 It is more preferable that the ring is a benzene ring which may have the following formula:

[0035] In general formula (1), n ​​is preferably 1 or 2, and more preferably 1.

[0036] The composition of the present disclosure contains, as a monofluorosulfonylating agent, a compound represented by the following general formula (2a): [ka] (In general formula (2a), X 11 is a nitrogen atom or C(R 11 ) and X 12 is a nitrogen atom or C(R 12 ) and Y 11 is a nitrogen atom or C(R 13 ) and Y 12 is a nitrogen atom or C(R 14 ) and R 11 ~R 14are each independently a hydrogen atom or a monovalent substituent, R 11 ~R 14 at least one of the following is present as a monovalent substituent, and q of the monovalent substituents are electron-withdrawing groups represented by EWG, where q is an integer of 1 to 4; and / or a compound represented by the following general formula (2b): [ka] (In general formula (2b), X 21 is a nitrogen atom or C(R 21 ) and X 22 is a nitrogen atom or C(R 22 ) and X 23 is a nitrogen atom or C(R 23 ) and X 24 is a nitrogen atom or C(R 24 ) and Y 21 is a nitrogen atom or C(R 25 ) and Y 22 is a nitrogen atom or C(R 26 ) and R 21 ~R 26 are each independently a hydrogen atom or a monovalent or divalent substituent, R 21 ~R 26 two adjacent substituents are divalent substituents, and they may be bonded to each other to form a ring, and the ring may be formed by a monovalent substituent R 27 and R 27 R when there are multiple 27 may be the same or different, R 21 ~R 27 at least one of the following is present as a monovalent substituent, and r of the monovalent substituents are electron-withdrawing groups represented by EWG, where r is an integer of 1 or more.

[0037] In the general formulae (2a) and (2b), the electron-withdrawing group represented by EWG is the same as the electron-withdrawing group described above in the general formula (1).

[0038] In general formula (2a), q represents the number of electron-withdrawing groups, represented by EWG, contained in the compound represented by general formula (2a), and is an integer of 1 to 4. q is preferably an integer of 1 to 3, and more preferably 1 or 2. For example, R 11 , R 12 It is further preferred that either or each of the following is an electron withdrawing group:

[0039] In general formula (2a), X 11 , X 12 , Y 11 , Y 12 Among these, usually 0 to 3 are nitrogen atoms, preferably 0 to 2 are nitrogen atoms, more preferably 1 or 2 are nitrogen atoms, and even more preferably 1 is a nitrogen atom. For example, X 11 is C(R 11 ) and X 12 is C(R 12 ) is preferable. 11 , Y 12 Preferably, one or both of Y are nitrogen atoms. 11 is a nitrogen atom, and Y 12 is C(R 14 ) or Y 11 is C(R 13 ) and Y 12 is a nitrogen atom or Y 11 and Y 12 are preferably nitrogen atoms. 11 , Y 12 More preferably, one of Y is a nitrogen atom, 11 is C(R 13 ) and Y 12 It is more preferred that is a nitrogen atom.

[0040] For example, X 11 is C(R 11 ) and R 11 is a hydrogen atom, and X 12 is C(R 12 ) and R 12is a nitro group, which is an electron-withdrawing group represented by EWG, and Y 11 is C(R 13 ) and R 13 is a hydrogen atom, and Y 12 is preferably a nitrogen atom, and q is preferably 1. This compound is obtained by the monofluorosulfonylation reaction of 4-nitroimidazole, and is also referred to as 4-nitroimidazole SO2F in this specification. This suppresses the generation of by-products and significantly improves the yield, and the reason for this is presumed to be as follows: the azole eliminated from the compound has a nitro group, which is a polar functional group, and therefore has low solubility in the reaction solution and precipitates, making it less likely to react with the target monofluorosulfonyl group, thereby suppressing the generation of by-products.

[0041] R 11 ~R 14 The monovalent substituent in is preferably a linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, a branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, an aromatic heterocyclic group having 4 to 9 carbon atoms, or an electron-withdrawing group. The linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, the branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, the aromatic hydrocarbon group having 6 to 14 carbon atoms, and the aromatic heterocyclic group having 4 to 9 carbon atoms are the same as the linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, the branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, the aromatic hydrocarbon group having 6 to 14 carbon atoms, and the aromatic heterocyclic group having 4 to 9 carbon atoms described above in general formula (1), respectively.

[0042] R 11 ~R 14 The monovalent substituent in is preferably a linear alkyl group having 1 to 6 carbon atoms, a branched alkyl group having 3 to 6 carbon atoms, or an electron-withdrawing group, and more preferably a methyl group, an ethyl group, an n-propyl group, an isopropyl group, or an electron-withdrawing group.

[0043] Preferred examples of the azole skeleton of the compound represented by general formula (2a) include, but are not limited to, the following.

[0044] [ka]

[0045] In the general formula (2a-2), R represents R in the general formula (2a). 13 is the same as: Among these, the compound represented by general formula (2a) preferably has an azole skeleton represented by general formula (2a-1) or an azole skeleton represented by general formula (2a-2).

[0046] In general formula (2b), r represents the number of electron-withdrawing groups, represented by EWG, that the compound represented by general formula (2b) has, and is an integer of 1 or more, preferably an integer of 1 to 5, more preferably an integer of 1 to 3, even more preferably 1 or 2, and still more preferably 1. For example, R 22 , R 23 It is particularly preferred that either of the groups is an electron-withdrawing group.

[0047] In general formula (2b), X 21 , X 22 , X 23 , X 24 , Y 21 , Y 22 Among these, typically 0 to 5 are nitrogen atoms, preferably 0 to 3 are nitrogen atoms, more preferably 0 to 2 are nitrogen atoms, even more preferably 1 or 2 are nitrogen atoms, and still more preferably 1 is a nitrogen atom. For example, X 21 is C(R 21 ) and X 22 is C(R 22 ) and X 23 is C(R 23 ) and X 24 is C(R 24 ) is preferable. 21 , Y 22 Preferably, one or both of Y are nitrogen atoms. 21 is a nitrogen atom, and Y22 is C(R 26 ) or Y 21 is C(R 25 ) and Y 22 is a nitrogen atom or Y 21 and Y 22 are preferably nitrogen atoms. 21 , Y 22 More preferably, one of Y is a nitrogen atom, 21 is a nitrogen atom, and Y 22 is C(R 26 ) is more preferable.

[0048] R 21 ~R 26 The monovalent substituent in is preferably a linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, a branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, an aromatic heterocyclic group having 4 to 9 carbon atoms, or an electron-withdrawing group. The linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, the branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, the aromatic hydrocarbon group having 6 to 14 carbon atoms, and the aromatic heterocyclic group having 4 to 9 carbon atoms are the same as the linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, the branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, the aromatic hydrocarbon group having 6 to 14 carbon atoms, and the aromatic heterocyclic group having 4 to 9 carbon atoms described above in general formula (1), respectively.

[0049] R 21 ~R 26 The monovalent substituent in is preferably a linear alkyl group having 1 to 6 carbon atoms, a branched alkyl group having 3 to 6 carbon atoms, or an electron-withdrawing group, and more preferably a methyl group, an ethyl group, an n-propyl group, an isopropyl group, or an electron-withdrawing group.

[0050] R 21 ~R 26 Any two adjacent R groups may be divalent substituents, and these may be bonded to each other to form a ring. 21 ~R 26 The two adjacent ones of are R 21 and R 22 Two adjacent R22 and R 23 Two adjacent R 23 and R 24 Two adjacent R 25 and R 26 Two adjacent ones of R are listed. 21 ~R 26 The ring formed by bonding two adjacent rings is not particularly limited, but examples thereof include aromatic hydrocarbon rings having 6 to 14 carbon atoms (e.g., benzene ring, naphthalene ring, anthracene ring) and aromatic heterocyclic rings having 4 to 9 carbon atoms (e.g., pyrrole ring, pyrazine ring, pyrimidine ring, pyridazine ring). 27 The number of carbon atoms of the substituent is not included in the number of carbon atoms of the ring.

[0051] R 27 is preferably a linear alkyl group having 1 to 6 carbon atoms, a branched alkyl group having 3 to 6 carbon atoms, or an electron-withdrawing group.

[0052] Examples of the linear alkyl group having 1 to 6 carbon atoms and the branched alkyl group having 3 to 6 carbon atoms include the examples of the linear alkyl group having 1 to 6 carbon atoms and the branched alkyl group having 3 to 6 carbon atoms described above in general formula (1), respectively.

[0053] R 27 is preferably a methyl group, an ethyl group, an n-propyl group, an isopropyl group, or an electron-withdrawing group.

[0054] R 21 ~R 26 is preferably a hydrogen atom or a monovalent substituent.

[0055] Preferred examples of the azole skeleton of the compound represented by general formula (2b) include, but are not limited to, the following.

[0056] [ka]

[0057] In the general formulas (2b-1) to (2b-3), R represents R in the general formula (2b). 21 ~R 24 The same applies to the hydrogen atom or monovalent substituent in the above formula (I). Among these, the compound represented by general formula (2b) preferably has an azole skeleton represented by general formula (2b-2).

[0058] From the viewpoint of achieving a higher yield of the target product, the composition of the present disclosure preferably contains a compound represented by the above general formula (2a).

[0059] The compound represented by the above general formula (1) (preferably, the compound represented by the above general formula (2a) and / or the compound represented by the general formula (2b); the same applies hereinafter) can be simply produced in one step by a monofluorosulfonylation reaction of an azole as shown in the following reaction formula:

[0060] [ka]

[0061] The monofluorosulfonylation reaction is preferably carried out in the presence of a base. Suitable examples of the base include inorganic bases such as sodium carbonate. The monofluorosulfonylation reaction is also preferably carried out using a reaction solvent. The reaction solvent is not particularly limited, but is preferably a nitrile solvent or a ketone solvent, and more preferably acetonitrile or acetone.

[0062] The amount of sulfuryl fluoride (SO2F2) used is not particularly limited, but is preferably 1 to 20 mol, more preferably 1.1 to 5 mol, per 1 mol of the raw material compound represented by general formula (1a).

[0063] The amount of base used is not particularly limited, but is preferably 1 to 20 mol, more preferably 1.5 to 5 mol, per mol of the raw material compound represented by general formula (1a).

[0064] The reaction time for the monofluorosulfonylation reaction can be, for example, 10 minutes to 80 hours, and preferably 3 to 24 hours.

[0065] By using a monofluorosulfonylation agent composition containing the compound represented by the above-mentioned general formula (1), it becomes possible to monofluorosulfonylate a substrate having a phenolic hydroxyl group or the like. One preferred embodiment of the present disclosure is a monofluorosulfonylation agent composition containing the compound represented by the above-mentioned general formula (1) and a base. The base is preferably a non-nucleophilic strong base.

[0066] A monofluorosulfonylating agent composition (hereinafter also referred to as a monofluorosulfonylating agent composition, or simply a composition) further containing a specific base can selectively monofluorosulfonylate a phenolic hydroxyl group while suppressing the production of by-products. Furthermore, since the monofluorosulfonylating agent composition contains the specific base, a method for producing a monofluorosulfonyloxy compound can be provided that is highly reproducible and excellent in yield.

[0067] In this specification, the phrase "selectively reacts" with a monofluorosulfonylation agent with a phenolic hydroxyl group means that the monofluorosulfonylation reaction proceeds preferentially with the phenolic hydroxyl group. The composition of the present disclosure contains a compound represented by general formula (1). Two or more types of compounds represented by general formula (1) may be combined. The compound represented by general formula (1) preferably accounts for 80% or more, and more preferably 90% or more, of the total mass of the composition.

[0068] (base) The monofluorosulfonylating agent composition of the present disclosure may contain a base. The base may be an inorganic base or an organic base. Examples of inorganic bases include alkali metal carbonates such as lithium carbonate, sodium carbonate, and potassium carbonate; and alkali metal alkoxides such as lithium methoxide, sodium methoxide, potassium methoxide, lithium ethoxide, sodium ethoxide, potassium ethoxide, lithium isopropoxide, sodium isopropoxide, potassium isopropoxide, lithium tert-butoxide, sodium tert-butoxide, and potassium tert-butoxide. Examples of organic bases include trimethylamine, triethylamine, diisopropylethylamine, tri-n-propylamine, 4-dimethylaminopyridine, and specific examples of non-nucleophilic strong bases described below. Among these, non-nucleophilic strong bases are preferred as the base. Two or more types of bases may be used in combination.

[0069] In this specification, a non-nucleophilic strong base refers to a base in which the nucleophilicity of the lone electron pair on the nitrogen atom is weak due to steric hindrance and the basicity (pKaH of the proton adduct of the non-nucleophilic strong base) is within the preferred numerical range described below.

[0070] The non-nucleophilic strong base is preferably a compound represented by the following general formula (A). [ka] (In general formula (A), R 100 ~R 102 are each independently a hydrogen atom, a linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, a branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 4 to 9 carbon atoms; R 103 represents a hydrogen atom, a linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, a branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, an aromatic heterocyclic group having 4 to 9 carbon atoms, or NR 104 R 105 and R 104 , R 105are each independently a hydrogen atom, a linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, a branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, an aromatic hydrocarbon group having 6 to 14 carbon atoms, or an aromatic heterocyclic group having 4 to 9 carbon atoms; R 100 and R 101 may be bonded to form a ring, and R 102 and R 103 may be bonded to form a ring.

[0071] R 100 ~R 105 The linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, the branched aliphatic hydrocarbon group having 3 to 6 carbon atoms, the aromatic hydrocarbon group having 6 to 14 carbon atoms, and the aromatic heterocyclic group having 4 to 9 carbon atoms are the same as those explained in the general formula (1).

[0072] R 100 ~R 102 is preferably a hydrogen atom or a linear aliphatic hydrocarbon group having 1 to 6 carbon atoms, more preferably a hydrogen atom or a linear aliphatic hydrocarbon group having 1 to 3 carbon atoms, and even more preferably a hydrogen atom or a linear aliphatic hydrocarbon group having 1 to 2 carbon atoms. 103 is NR 104 R 105 Preferably, R 104 , R 105 is preferably a hydrogen atom or a straight-chain aliphatic hydrocarbon group having 1 to 6 carbon atoms, more preferably a hydrogen atom or a straight-chain aliphatic hydrocarbon group having 1 to 3 carbon atoms, and even more preferably a hydrogen atom or a straight-chain aliphatic hydrocarbon group having 1 to 2 carbon atoms. As the straight-chain aliphatic hydrocarbon group, a straight-chain alkyl group is preferred.

[0073] In a more preferred embodiment, R 100 and R 101 are bonded to form a ring, or R 102 and R 103 are preferably bonded to form a ring, and R 100 and R 101 are bonded to form a ring, and R 102 and R 103 More preferably, R are bonded to form a ring. 100 and R 101are bonded to form a ring, and R 102 and R 103 When these are bonded to form a ring, the compound represented by the general formula (A) becomes a compound represented by the following general formula (A-1). [ka] (In general formula (A-1), R 106 , R 107 are each independently a divalent group.

[0074] R 100 and R 101 The group formed by bonding (R 106 ), R 102 and R 103 The group formed by bonding (R 107 ) is not particularly limited as long as it is a divalent group, and examples thereof include divalent hydrocarbon groups which may contain heteroatoms. The hydrocarbon group preferably has 2 to 15 carbon atoms, more preferably 3 to 10 carbon atoms, and even more preferably 3 to 6 carbon atoms.

[0075] Examples of the hydrocarbon group include an alkylene group, an alkenylene group, an alkynylene group, etc. Among these, an alkylene group is preferred.

[0076] Examples of the alkylene group include an ethylene group, a propylene group, a butylene group, a pentylene group, a hexylene group, a heptylene group, an octylene group, a nonylene group, a decylene group, etc. Among these, a propylene group, a butylene group, and a pentylene group are preferred.

[0077] Examples of the alkenylene group include a 1-propenylene group, a 2-propenylene group, a 1-butenylene group, a 2-butenylene group, a 1-pentenylene group, a 2-pentenylene group, a 1-hexenylene group, a 2-hexenylene group, and a 1-octenylene group.

[0078] Examples of the alkynylene group include an ethynylene group, a propynylene group, a butynylene group, a pentynylene group, a hexynylene group, a heptynylene group, an octynylene group, a nonynylene group, a decynylene group, an undecynylene group, and a dodecynylene group.

[0079] The hydrocarbon group may contain heteroatoms, but preferably does not contain heteroatoms, such as nitrogen atoms, oxygen atoms, sulfur atoms, halogen atoms (fluorine atoms, chlorine atoms, bromine atoms, iodine atoms), and silicon atoms.

[0080] Regarding the compound represented by the general formula (A-1), R 106 , R 107 In the compound represented by the general formula (A), R 100 and R 101 are bonded to form a ring, or R 102 and R 103 When R is bonded to form a ring, that is, when only one ring is formed, 106 , R 107 is the same as in the case of the compound represented by the general formula (A-1), including preferred embodiments.

[0081] The compound represented by the general formula (A) is not particularly limited, and examples thereof include, in addition to the compounds having a heterocyclic group having 4 or more carbon atoms described below, 1,1,3,3-tetramethylguanidine, 1,1,3,3-tetraethylguanidine, 1,1,3,3-tetrapropylguanidine, 1,1,3-trimethylguanidine, 1,3,3-trimethylguanidine, 1,1,3-triethylguanidine, 1,3,3-triethylguanidine, 1,1,3-tripropylguanidine, and 1,3,3-tripropylguanidine.

[0082] The non-nucleophilic strong base is preferably an organic base, more preferably a heterocyclic group-containing organic base, still more preferably a compound having a heterocyclic group with 4 or more carbon atoms, and particularly preferably a compound having a nitrogen atom and a heterocyclic group with 4 or more carbon atoms. Specific examples include 1,8-diazabicyclo[5.4.0]undecene, 1,5-diazabicyclo[4.3.0]nonene, pyridine, 2,3-lutidine, 2,4-lutidine, 2,5-lutidine, 2,6-lutidine, 3,4-lutidine, 3,5-lutidine, 2,3,4-collidine, 2,4,5-collidine, 2,5,6-collidine, 2,4,6-collidine, 3,4,5-collidine, and 3,5,6-collidine.

[0083] Use of the heterocyclic group-containing organic base tends to provide a method for producing a monofluorosulfonyloxy compound with better reproducibility and excellent yield.

[0084] A non-nucleophilic strong base with a higher basicity tends to provide more favorable reproducibility and excellent yield, and therefore the pKaH of the proton adduct of the non-nucleophilic strong base is preferably 9.0 or more, more preferably 10.0 or more, even more preferably 11.0 or more, particularly preferably 12.0 or more, and most preferably 13.0 or more, and the upper limit is not particularly limited, but is, for example, 37 or less. The reason why a non-nucleophilic strong base with a high basicity tends to provide better reproducibility and yield is presumed to be as follows: In the presence of a highly basic non-nucleophilic strong base, the hydroxyl group of the aromatic hydroxyl compound represented by general formula (3), which is highly acidic, is deprotonated to generate a phenoxide ion, which is likely to coexist. In this case, since the reactivity of the compound represented by general formula (1) is relatively low, the reaction proceeds preferentially with the phenoxide ion, which is the most nucleophilic present in the system. On the other hand, if the aromatic hydroxyl compound represented by general formula (3) has an amino group, the amino group is not deprotonated and remains as an amino group, and cannot react with the compound represented by general formula (1), which is relatively low in reactivity. In this way, it is presumed that the presence of a highly basic non-nucleophilic strong base selectively deprotonates the hydroxyl group of the aromatic hydroxyl compound represented by general formula (3) to generate a phenoxide ion, which results in the reaction proceeding selectively at the hydroxyl group. In this specification, the pKaH of a proton adduct of a non-nucleophilic strong base is measured at 25°C by dissolving the non-nucleophilic strong base in dimethyl sulfoxide (DMSO).

[0085] The non-nucleophilic strong base is preferably liquid at 25° C. Use of a non-nucleophilic strong base (preferably a non-nucleophilic strong organic base) that is liquid at 25° C. tends to provide a method for producing a monofluorosulfonyloxy compound with more favorable reproducibility and excellent yield. In this specification, "liquid at 25°C" means something that has fluidity at 25°C, and includes creamy and paste-like substances.

[0086] Non-nucleophilic strong bases include 1,8-diazabicyclo[5.4.0]undecene (DBU) (pKaH = 13.9), 1,5-diazabicyclo[4.3.0]nonene (DBN) (pKaH = 13.4), 1,1,3,3-tetramethylguanidine (TMG) (pKaH = 13.6), 2-tert-butyl-1,1,3,3-tetramethylguanidine, 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) (pKaH = 15.3), 7-methyl-1, It is preferably any one selected from the group consisting of 5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) (pKaH=14.8), imino-tris(dimethylamino)phosphorane (pKaH=16.4), phosphazene base P1-t-Bu (pKaH=15.7), phosphazene base P2-t-Bu, phosphazene base P4-t-Bu (pKaH=30.25), and lithium diisopropylamide (LDA) (pKaH=36, THF). Among these, 1,8-diazabicyclo[5.4.0]undecene (DBU) (pKaH=13.9), 1,5-diazabicyclo[4.3.0]nonene (DBN) (pKaH=13.4), or 1,1,3,3-tetramethylguanidine (TMG) (pKaH=13.6) is preferred, and 1,8-diazabicyclo[5.4.0]undecene (DBU) (pKaH=13.9) is particularly preferred. These bases can be used alone or in combination.

[0087] In the monofluorosulfonylation agent composition of the present disclosure, the total content of non-nucleophilic strong bases in 100 mol% of bases is preferably 80 mol% or more, more preferably 90 mol% or more, even more preferably 95 mol% or more, particularly preferably 98 mol% or more, and most preferably 100 mol%, because this allows the effects of the present disclosure to be more suitably obtained.

[0088] The amount of base used is not particularly limited, but is usually preferably 0.01 to 30 mol, more preferably 0.01 to 25 mol, and even more preferably 1 to 20 mol, per 1 mol of the compound to be monofluorosulfonated (described below). Note that, as described below, under certain conditions, it may be preferable to use a catalytic amount of base.

[0089] The composition of the present disclosure may further comprise a solvent. The solvent is not particularly limited as long as it dissolves the compound represented by the general formula (1) and the base, and examples thereof include the reaction solvents for monofluorosulfonylation described below.

[0090] <Method of producing monofluorosulfonyloxy compound> A method for producing a monofluorosulfonyloxy compound using the composition of the present disclosure (hereinafter also referred to as the production method) includes a step of reacting the above-mentioned monofluorosulfonylating agent composition with a compound represented by the following general formula (3):

[0091] (Monofluorosulfonyl compounds) The compound to be monofluorosulfonylated with the monofluorosulfonylating agent composition (hereinafter also referred to as the compound to be monofluorosulfonated) is an aromatic hydroxyl compound represented by the following general formula (3). General formula (3): Ar-OH (3) In the general formula (3), Ar represents an aromatic ring group or a substituted aromatic ring group.

[0092] In the aromatic ring hydroxyl compound represented by the general formula (3), Ar represents an aromatic ring group or a substituted aromatic ring group. The aromatic ring group is not particularly limited, and may be monocyclic or polycyclic. An aromatic ring group having 1 to 18 carbon atoms is preferable. Examples thereof include aromatic hydrocarbon groups such as a phenyl group, a naphthyl group, and an anthryl group, and aromatic heterocyclic groups containing a heteroatom such as a nitrogen atom, an oxygen atom, or a sulfur atom, such as a pyrrolyl group (including nitrogen-protected forms), a pyridyl group, a pyrazyl group, a pyrimidyl group, a pyridazyl group, a triazyl group, a furyl group, a thienyl group, an indolyl group (including nitrogen-protected forms), an indazolyl group, a quinolyl group, a carbazolyl group, a pyrrolopyridyl group, a benzofuryl group, and a benzothienyl group. In the above general formula (3), Ar represents an aromatic ring group, and the aromatic ring group is preferably an aromatic heterocyclic group.

[0093] The substituted aromatic ring group has any number and any combination of substituents on any carbon or nitrogen atom of the aromatic ring group, such as halogen atoms (fluorine, chlorine, bromine, and iodine), lower alkyl groups (methyl, ethyl, and propyl), lower unsaturated groups (vinyl, allyl, and propargyl), lower haloalkyl groups (fluoromethyl, chloromethyl, and bromomethyl), C(CF)OH (including protected hydroxyl groups), lower alkoxy groups (methoxy, ethoxy, and propoxy), lower haloalkoxy groups (fluoromethoxy, chloromethoxy, and bromomethoxy), lower acyloxy groups (formyloxy, acetyloxy, propionyloxy, and butyryloxy), cyano, methoxycarbonyl, ethoxycarbonyl, and propargyl. lower alkoxycarbonyl groups such as methoxycarbonylmethyl, ethoxycarbonylethyl, and propoxycarbonylpropyl groups, aromatic ring groups such as β-D-glucopyranoside group, phenyl group, naphthyl group, anthryl group, pyrrolyl group (including nitrogen-protected groups), pyridyl group, furyl group, thienyl group, indolyl group (including nitrogen-protected groups), quinolyl group, benzofuryl group, and benzothienyl group, protected carboxyl groups, amino groups, protected amino groups, lower alkylamino groups, lower alkylamino-lower alkyl groups, hydroxyl groups, protected hydroxyl groups, and X'-Ar'-OH group. These substituents may be further substituted, for example, with the substituents of "such substituents" above.

[0094] In the above general formula (3), it is preferred that Ar represents a substituted aromatic ring group, and the substituent of the substituted aromatic ring group is a lower alkyl group, a lower alkoxycarbonyl lower alkyl group, a β-D-glucopyranoside group, an amino group, a lower alkylamino group, or a hydroxyl group.

[0095] In the X'-Ar'-OH group, X' represents a C(CH3)2 group, a C(CF3)2 group, an oxygen atom, a nitrogen atom (including nitrogen-protected atoms), a sulfur atom, an SO group, or an SO2 group, and Ar' represents a phenylene group or a substituted phenylene group. The substitution position of the phenylene group is the 2nd, 3rd, or 4th position relative to the hydroxyl group. The substituents of the substituted phenylene group are the same as those of the substituted aromatic ring group described above. Specific examples of aromatic hydroxyl compounds represented by general formula (3) substituted with an X'-Ar'-OH group include the following compounds.

[0096] [ka]

[0097] In this specification, "lower" means a linear or branched chain or cyclic (when the carbon number is 3 or more) group having 1 to 6 carbon atoms. The aromatic ring group in the "substituents" section can also be substituted with a halogen atom, a lower alkyl group, a lower unsaturated group, a lower haloalkyl group, a C(CF)OH group (including a protected hydroxyl group), a lower alkoxy group, a lower haloalkoxy group, a formyloxy group, a lower acyloxy group, a cyano group, a lower alkoxycarbonyl group, a lower alkoxycarbonyl lower alkyl group, a protected carboxyl group, a protected amino group, a hydroxyl group, a protected hydroxyl group, and an X'-Ar'-OH group. Protective groups for pyrrolyl, indolyl, hydroxyl, carboxyl, and amino groups are those described in Protective Groups in Organic Synthesis, Third Edition, 1999, John Wiley & Sons, Inc., and the like. Among these, aromatic ring groups and substituted aromatic ring groups excluding "hydroxyl groups", "aromatic ring groups", and "X'-Ar'-OH groups" as substituents are preferred, and aromatic hydrocarbon groups and substituted aromatic hydrocarbon groups (aromatic hydrocarbon groups having a substituent) excluding "hydroxyl groups", "aromatic ring groups", and "X'-Ar'-OH groups" as substituents are particularly preferred. In aromatic ring hydroxyl compounds having multiple hydroxyl groups, multiple fluorosulfonylation reactions may proceed depending on the reaction conditions used.

[0098] In a preferred embodiment, the aromatic ring hydroxyl compound represented by the general formula (3) has at least one substituent selected from an alcoholic hydroxyl group and an amino group. These substituents may be further substituted, for example, with the substituents described above as "such substituents."

[0099] Examples of compounds represented by general formula (3) are shown below, but the compounds are not limited to these.

[0100] [ka]

[0101] In the monofluorosulfonylation reaction, the aromatic hydroxyl compound represented by the general formula (3) is preferably used in an amount of 0.7 mol to 1.2 mol, more preferably 0.8 mol to 1.0 mol, per 1.0 mol of the monofluorosulfonyl compound represented by the general formula (1).

[0102] (solvent) The above-mentioned monofluorosulfonylation reaction is preferably carried out using a reaction solvent. Examples of reaction solvents for monofluorosulfonylation include ether solvents, aliphatic hydrocarbon solvents, aromatic hydrocarbon solvents, halogenated hydrocarbon solvents, ester solvents, amide solvents, nitrile solvents, sulfoxide solvents, and ketone solvents.

[0103] Specific examples of these reaction solvents include ether solvents such as diethyl ether, diisopropyl ether, dibutyl ether, tert-butyl methyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, tetrahydropyran, 1,4-dioxane, and cyclopentyl methyl ether. Examples of the aliphatic hydrocarbon solvent include n-hexane, n-heptane, n-pentane, n-nonane, and n-decane. Examples of aromatic hydrocarbon solvents include toluene, xylene, mesitylene, and ethylbenzene. Examples of halogenated hydrocarbon solvents include methylene chloride (dichloromethane), chloroform, and 1,2-dichloroethane. Examples of the ester solvent include ethyl acetate, isopropyl acetate, n-butyl acetate, and γ-butyrolactone. Examples of amide solvents include N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, and 1,3-dimethyl-2-imidazolidinone. Examples of nitrile solvents include acetonitrile, propionitrile, and benzonitrile. An example of the sulfoxide solvent is dimethyl sulfoxide. An example of the ketone solvent is acetone. Among these, nitrile solvents are preferred, and acetonitrile is particularly preferred, because they are easily available and have excellent solubility for the substrate and the monofluorosulfonylation agent of the present disclosure. These reaction solvents can be used alone or in combination.

[0104] The amount of reaction solvent used for monofluorosulfonylation is not particularly limited, but 0.05 L (liter) or more may be used per mole of the compound to be monofluorosulfonated, and usually 0.1 to 20 L is preferred, and particularly 0.1 to 10 L is more preferred.

[0105] (base) The above-mentioned monofluorosulfonylation reaction is preferably carried out using the above-mentioned base. The base may be contained in the monofluorosulfonylating agent composition of the present disclosure, or may be added to the reaction system at the start of the reaction or during the reaction. The preferred amount of base used is basically as described above. However, when the compound represented by general formula (1) is 4-nitroimidazole SO2F and dichloromethane is used as the solvent, it is particularly preferable to use a catalytic amount of DBU as the base (preferably 0.05 to 0.5 mol, more preferably 0.15 to 0.4 mol per 1 mol of the compound to be monofluorosulfonated). This makes the effects of the present disclosure particularly excellent.

[0106] (Reaction temperature) The reaction temperature for monofluorosulfonylation is not particularly limited, but is preferably 150°C or lower, more preferably in the range of -100 to 150°C, even more preferably -78 to 100°C, and particularly preferably 0 to 50°C.

[0107] (Reaction time) The reaction time for monofluorosulfonylation is not particularly limited, but may be in the range of 0.1 to 72 hours. Since the reaction time varies depending on the raw materials and reaction conditions, it is preferable to follow the progress of the reaction by analytical means such as gas chromatography, liquid chromatography, or NMR, and determine the end point as the time when the raw materials have almost completely disappeared.

[0108] (Post-processing operations) After the above reaction, a post-treatment procedure for isolating the monofluorosulfonyloxy compound may be carried out according to a general procedure used in organic synthesis. For example, when the reaction is carried out in a heterogeneous reaction mixture, it is preferable to carry out filtration.

[0109] The obtained monofluorosulfonyloxy compound can be suitably used in, for example, coupling reactions using transition metals. As described above, the monofluorosulfonyloxy compound obtained by the production method of the present disclosure makes it possible to produce a coupling reaction product much more efficiently than by conventional methods.

[0110] <New compound> The present disclosure also relates to a compound represented by any one of the following general formulas (4a) to (4d). [ka] In general formula (4a), R represents an alkyl group having 1 to 8 carbon atoms. R preferably represents a methyl group. The NO2 group is bonded to a carbon atom on the ring to which R is not bonded, and is preferably bonded to the 4th position on the ring. In general formula (4d), the NO2 group is bonded to a carbon atom on the six-membered ring to which no nitrogen atom is bonded, and is preferably bonded to the 4th or 5th position on the ring. [Example]

[0111] Hereinafter, the present disclosure will be described in detail with reference to examples, but the present disclosure is not limited to these examples. Herein, in the examples and comparative examples, the NMR yield (%) is the yield of the nuclear magnetic resonance spectrum 1 H-NMR or 19 F-NMR analysis confirmed the internal standard method ( 1 H-NMR analysis and 19 In F-NMR, the value was obtained by quantifying using 1,4-bistrifluoromethylbenzene as an internal standard.

[0112] [Example 1] 3.18 g (28.1 mmol, 1.0 eq.) of 4-nitroimidazole as the substrate, 7.46 g (70.3 mmol, 2.5 eq.) of sodium carbonate, and 28 mL of acetonitrile as the reaction solvent were placed in a 200 mL stainless steel (SUS) pressure vessel. Subsequently, 7.18 g (70.3 mmol, 2.5 eq.) of sulfuryl fluoride gas was slowly introduced from a cylinder, and the mixture was stirred overnight at room temperature. The reaction mixture was filtered through Celite while rinsing with 56 mL of acetonitrile, and the filtrate was concentrated under reduced pressure. The crude product obtained by concentration was purified by silica gel column chromatography, and the solution containing the target product was concentrated to obtain 3.51 g of 4-nitroimidazole-1-sulfonyl fluoride in 64% isolation yield.

[0113] [Physical Properties] 1 H-NMR(400MHz,d6-acetone)δ(ppm):8.63(1H,d,J=1.6Hz),8.99(1H,d,J=1.6Hz) 19 F-NMR(400MHz,d6-acetone)δ(ppm):59.2(1F,s)

[0114] The reaction in Example 1 is shown below.

[0115] [ka]

[0116] [Example 2] 0.93 g (7.33 mmol, 1.0 eq.) of 2-methyl-4-nitroimidazole as the substrate, 1.94 g (18.3 mmol, 2.5 eq.) of sodium carbonate, and 7.3 mL of acetonitrile as the reaction solvent were placed in a 50 mL stainless steel (SUS) pressure vessel. Then, 1.87 g (18.3 mmol, 2.5 eq.) of sulfuryl fluoride gas was gradually added from a cylinder, and the mixture was stirred overnight at room temperature. The reaction mixture was filtered through Celite while washing with 15 mL of acetonitrile, and the filtrate was concentrated under reduced pressure. Concentration afforded 1.37 g of 2-methyl-4-nitroimidazole sulfonyl fluoride in an 87% isolated yield.

[0117] [Physical Properties] 1 H-NMR(400MHz,d6-acetone)δ(ppm):2.62(3H,s),8.37(1H,s) 19 F-NMR(400MHz,d6-acetone)δ(ppm):58.8(1F,s)

[0118] The reaction in Example 2 is shown below.

[0119] [ka]

[0120] [Example 3] 0.52 g (3.78 mmol, 1.0 eq.) of 4,5-dichloroimidazole as the substrate, 1.00 g (9.44 mmol, 2.5 eq.) of sodium carbonate, and 3.8 mL of acetonitrile as the reaction solvent were placed in a 20 mL stainless steel (SUS) pressure vessel. Then, 0.96 g (9.44 mmol, 2.5 eq.) of sulfuryl fluoride gas was gradually added from a cylinder, and the mixture was stirred overnight at room temperature. The reaction mixture was filtered through Celite while washing with 12 mL of acetonitrile, and the filtrate was concentrated under reduced pressure. Concentration afforded 0.68 g of 4,5-dichloroimidazole sulfonyl fluoride in an 82% isolated yield.

[0121] [Physical Properties] 1 H-NMR(400MHz,d6-acetone)δ(ppm):8.46(1H,s) 19 F-NMR(400MHz,d6-acetone)δ(ppm):56.8(1F,s)

[0122] The reaction in Example 3 is shown below.

[0123] [ka]

[0124] [Example 4] 0.37 g (2.72 mmol, 1.0 eq.) of 4-trifluoromethylimidazole as the substrate, 0.72 g (6.79 mmol, 2.5 eq.) of sodium carbonate, and 2.7 mL of acetonitrile as the reaction solvent were placed in a 20 mL stainless steel (SUS) pressure vessel. Then, 0.69 g (6.79 mmol, 2.5 eq.) of sulfuryl fluoride gas was gradually added from a cylinder, and the mixture was stirred overnight at room temperature. The reaction mixture was filtered through Celite while rinsing with 8 mL of acetonitrile, and the filtrate was concentrated under reduced pressure. Concentration afforded 0.52 g of 4-trifluoromethylimidazole sulfonyl fluoride in an 87% isolated yield.

[0125] [Physical Properties] 1 H-NMR(400MHz,d6-acetone)δ(ppm):8.54(1H,m),8.63(1H,s) 19 F-NMR(400MHz,d6-acetone)δ(ppm):58.8(1F,s),64.9(3F,s)

[0126] The reaction in Example 4 is shown below.

[0127] [ka]

[0128] [Example 5] 0.51 g (4.03 mmol, 1.0 eq.) of methyl 1H-imidazole-5-carboxylate as the substrate, 1.07 g (10.1 mmol, 2.5 eq.) of sodium carbonate, and 4.0 mL of acetonitrile as the reaction solvent were placed in a 20 mL stainless steel (SUS) pressure vessel. Subsequently, 1.03 g (10.1 mmol, 2.5 eq.) of sulfuryl fluoride gas was gradually added from a cylinder, and the mixture was stirred overnight at room temperature. The reaction mixture was filtered through Celite while washing with 12 mL of acetonitrile, and the filtrate was concentrated under reduced pressure. Concentration afforded 0.81 g of methyl 1-fluorosulfonyl-imidazole-5-carboxylate in a 96% isolated yield.

[0129] [Physical Properties] 1 H-NMR(400MHz,d6-acetone)δ(ppm):3.87(3H,s),8.44(1H,s),8.49(1H,s) 19 F-NMR(400MHz,d6-acetone)δ(ppm):58.5(1F,s)

[0130] The reaction in Example 5 is shown below.

[0131] [ka]

[0132] [Example 6] 0.61 g (3.74 mmol, 1.0 eq.) of 5-nitrobenzimidazole as the substrate, 0.99 g (9.35 mmol, 2.5 eq.) of sodium carbonate, and 3.7 mL of acetonitrile as the reaction solvent were placed in a 20 mL stainless steel (SUS) pressure vessel. Then, 0.95 g (9.35 mmol, 2.5 eq.) of sulfuryl fluoride gas was slowly introduced from a cylinder, and the mixture was stirred overnight at room temperature. The reaction mixture was filtered through Celite while rinsing with 11 mL of acetonitrile, and the filtrate was concentrated under reduced pressure. Concentration afforded 0.36 g of 4(5)-nitrobenzimidazole sulfonyl fluoride in 39% yield as a mixture of nitro positional isomers (major:minor = 56:44).

[0133] [Physical Properties] 1 H-NMR(400MHz,d6-acetone)δ(ppm):major:8.08~8.12(1H,m),8.48~8.52(1H,m),8.71(2H,s,J=2.9Hz),8.92(1H,s).minor:8.08~8.12(1H, m),8.44~8.47(1H,m),8.65(2H,s,J=2.1Hz),9.00(1H,s). 19 F-NMR(400MHz,d6-acetone)δ(ppm):major:57.0(1F,s).minor:57.4(1F,s)

[0134] The reaction in Example 6 is shown below.

[0135] [ka]

[0136] [Example 7] 0.49 g (3.00 mmol, 1.0 eq.) of 6-nitroindazole as the substrate, 0.48 g (4.50 mmol, 1.5 eq.) of sodium carbonate, and 3.0 mL of acetonitrile as the reaction solvent were placed in a 20 mL stainless steel (SUS) pressure vessel. Then, 0.37 g (3.60 mmol, 1.2 eq.) of sulfuryl fluoride gas was gradually added from a cylinder, and the mixture was stirred overnight at room temperature. The reaction mixture was filtered through Celite while washing with 10 mL of acetonitrile, and the filtrate was concentrated under reduced pressure. Concentration afforded 0.71 g of 6-nitroindazole sulfonyl fluoride in a 96% isolated yield.

[0137] [Physical Properties] 1 H-NMR(400MHz,d6-acetone)δ(ppm):8.14(1H, d,J=8.8Hz),8.31(1H,d,J=8.8Hz),8.68(1H,s),8.71(1H,s) 19 F-NMR(400MHz,d6-acetone)δ(ppm):54.2(1F,s)

[0138] The reaction in Example 7 is shown below.

[0139] [ka]

[0140] [Comparative Example 1] 20.4 g (300 mmol, 1.0 eq.) of imidazole as the substrate, 79.4 g (749 mmol, 2.5 eq.) of sodium carbonate, and 300 mL of acetonitrile as the reaction solvent were placed in a 2 L glass flask. Subsequently, 36.7 g (360 mmol, 1.2 eq.) of sulfuryl fluoride gas was slowly introduced via a balloon, and the mixture was stirred overnight at room temperature. 600 mL of dichloromethane and 300 mL of clean water were added to the reaction mixture, which was then transferred to a separatory funnel for layer separation. The resulting organic layer was washed with an additional 300 mL of clean water, and the resulting oil layer was dried over sodium sulfate. The resulting oil layer was filtered and concentrated under reduced pressure at 30 °C and 100 kPa to obtain the crude product. The crude product was subjected to flash distillation to obtain 28.0 g of imidazole sulfonyl fluoride with a GC purity of 99% in an isolation yield of 62%.

[0141] [Physical Properties] 1 H-NMR(400MHz,d6-acetone)δ(ppm):7.32(1H,d,J=1.1Hz),7.82(1H,t,J=1.6Hz),8.38(1H,s) 19 F-NMR(400MHz,d6-acetone)δ(ppm):57.5(1F,s)

[0142] The reaction in Comparative Example 1 is shown below.

[0143] [ka]

[0144] Comparative Example 2 11.6 g (141 mmol, 1.0 eq.) of 2-methylimidazole as the substrate, 22.4 g (211 mmol, 1.5 eq.) of sodium carbonate, and 141 mL of acetonitrile as the reaction solvent were collected and placed in a 500 mL stainless steel (SUS) pressure vessel. 17.3 g (169 mmol, 1.2 eq.) of sulfuryl fluoride gas was then slowly blown in from a cylinder, and the mixture was stirred at room temperature for 2 days. The reaction mixture was filtered through Celite while rinsing with 200 mL of acetonitrile, and the filtrate was concentrated under reduced pressure. Concentration afforded 13.4 g of 2-methylimidazole-1-sulfonyl fluoride in an isolated yield of 58%.

[0145] [Physical Properties] 1 H-NMR(400MHz,d6-acetone)δ(ppm):2.88(3H,s),7.02(1H,d,J=1.8Hz),7.59(1H,d,J=1.8Hz) 19 F-NMR(400MHz,d6-acetone)δ(ppm):56.8(1F,s)

[0146] The reaction in Comparative Example 2 is shown below.

[0147] [ka]

[0148] Comparative Example 3 10.3 g (84.9 mmol, 1.0 eq.) of benzimidazole as the substrate, 13.5 g (127 mmol, 1.5 eq.) of sodium carbonate, and 85 mL of acetonitrile as the reaction solvent were placed in a 500 mL stainless steel (SUS) pressure vessel. 10.4 g (102 mmol, 1.2 eq.) of sulfuryl fluoride gas was then slowly added from a cylinder, and the mixture was stirred overnight at room temperature. The reaction mixture was filtered through Celite while washing with 170 mL of acetonitrile, and the filtrate was concentrated under reduced pressure. Concentration afforded 13.2 g of benzimidazole sulfonyl fluoride in an isolated yield of 78%.

[0149] [Physical Properties] 1 H-NMR(400MHz,d6-acetone)δ(ppm):7.56~7.65(2H,m),7.86~7.90(2H,m),8.66(1H,s) 19 F-NMR(400MHz,d6-acetone)δ(ppm):55.1(1F,s)

[0150] The reaction in Comparative Example 3 is shown below.

[0151] [ka]

[0152] Comparative Example 4 0.16 g (1.30 mmol, 1.0 eq.) of indazole as the substrate, 0.21 g (2.00 mmol, 1.5 eq.) of sodium carbonate, and 1.4 mL of acetonitrile as the reaction solvent were placed in a 10 mL stainless steel (SUS) pressure vessel. Subsequently, 0.17 g (1.60 mmol, 1.2 eq.) of sulfuryl fluoride gas was gradually added from a cylinder, and the mixture was stirred overnight at room temperature. The reaction mixture was filtered through Celite while washing with 10 mL of acetonitrile, and the filtrate was concentrated under reduced pressure. Concentration afforded 0.26 g of indazole sulfonyl fluoride in a 96% isolated yield.

[0153] [Physical Properties] 1 H-NMR(400MHz,d6-acetone)δ(ppm):7.51(1H,t,J=8.0Hz),7.70(1H,d,J=8.4Hz),7.91~7.95(2H,m),8.55(1H,s) 19 F-NMR(400MHz,d6-acetone)δ(ppm):52.2(1F,s)

[0154] The reaction in Comparative Example 4 is shown below.

[0155] [ka]

[0156] [Example 8] 56 mg (0.40 mmol, 1.0 eq.) of 4-nitrophenol as the substrate and 2 mL of tetrahydrofuran as the reaction solvent were placed in a 20 mL glass flask equipped with a stir bar. Next, 70 mg (0.44 mmol, 1.1 eq.) of diazabicycloundecene was added to the flask and stirred at room temperature for 10 minutes. The corresponding azole monosulfonyl fluoride (0.60 mmol, 1.5 eq.) was then added and stirred at room temperature for 30 minutes. The resulting reaction solution was weighed and 21 mg of 1,4-bis-trifluoromethylbenzene was added as an internal standard and mixed. After filtration, the 4-nitrophenol sulfonyl monofluoride was quantified by NMR analysis.

[0157] [Physical Properties] 1 H-NMR(400MHz,d6-acetone)δ(ppm):7.66(2H,d,J=9.4Hz),8.34(2H,d,J=9.4Hz) 19 F-NMR(400MHz,d6-acetone)δ(ppm):38.7(1F,s)

[0158] The reaction in Example 8 is shown below.

[0159] [ka]

[0160] [Examples 9-14, Comparative Examples 5-8] Next, except for changing the azole monosulfonyl fluoride (azole compound), a monofluorosulfonylation reaction was carried out in the same manner as in Example 8. The NMR yield results are summarized in Table 1 below, together with Examples 8-14 and Comparative Examples 5-8. [Table 1]

[0161] [Example 15] 24 mg (0.21 mmol, 1.0 eq.) of 4-aminophenol as the substrate and 1 mL of deuterated acetonitrile as the reaction solvent were placed in a 20 mL glass flask equipped with a stir bar. Next, 36 mg (0.24 mmol, 1.1 eq.) of diazabicycloundecene was added to the flask and stirred at room temperature for 10 minutes. 63 mg (0.32 mmol, 1.5 eq.) of 4-nitroimidazole monosulfonyl fluoride was then added and stirred at room temperature for 30 minutes. The resulting reaction solution was weighed and 21 mg of 1,4-bis-trifluoromethylbenzene was added as an internal standard. After filtration, the 4-aminophenol sulfonyl monofluoride was quantified by NMR analysis, confirming that 31 mg of the corresponding phenol sulfonyl fluoride was produced in a quantitative yield of 74%.

[0162] [Physical Properties] 1 H-NMR(400MHz,d6-acetone)δ(ppm):6.66(2H,d,J=9.2Hz),7.09(2H,d,J=9.1Hz) 19 F-NMR(400MHz,d6-acetone)δ(ppm):34.8(1F,s)

[0163] The reaction in Example 15 is shown below.

[0164] [ka]

[0165] [Example 16] 35 mg (0.23 mmol, 1.0 eq.) of methyl 4-hydroxybenzoate as the substrate and 1 mL of deuterated acetonitrile as the reaction solvent were placed in a 20 mL glass flask equipped with a stir bar. Next, 39 mg (0.25 mmol, 1.1 eq.) of diazabicycloundecene was added to the flask and stirred at room temperature for 10 minutes. 67 mg (0.34 mmol, 1.5 eq.) of 4-nitroimidazole monosulfonyl fluoride was then added and stirred at room temperature for 30 minutes. The resulting reaction solution was weighed and 60 mg of 1,4-bis-trifluoromethylbenzene was added as an internal standard and mixed. After filtration, the methyl 4-fluorosulfonyloxybenzoate was quantified by NMR analysis, confirming that 41 mg of the corresponding sulfonyl fluoride of phenol was produced in a quantitative yield of 76%.

[0166] [Physical Properties] 1 H-NMR(400MHz,d3-acetonitrile)δ(ppm):3.86(3H,s),7.52(2H,d,J=8.0Hz),8.11(2H,d,J=8.9Hz) 19 F-NMR(400MHz,d3-acetonitrile)δ(ppm):37.8(1F,s)

[0167] The reaction in Example 16 is shown below.

[0168] [ka]

[0169] [Example 17] 30 mg (0.23 mmol, 1.0 eq.) of 4-chlorophenol as the substrate and 1 mL of deuterated acetonitrile as the reaction solvent were placed in a 20 mL glass flask equipped with a stir bar. Next, 39 mg (0.25 mmol, 1.1 eq.) of diazabicycloundecene was added to the flask and stirred at room temperature for 10 minutes. 67 mg (0.34 mmol, 1.5 eq.) of 4-nitroimidazole monosulfonyl fluoride was then added and stirred at room temperature for 30 minutes. The resulting reaction solution was weighed and 50 mg of 1,4-bis-trifluoromethylbenzene was added as an internal standard and mixed. After filtration, the 4-chlorophenol sulfonyl monofluoride was quantified by NMR analysis, confirming that 42 mg of the corresponding phenol sulfonyl fluoride was produced in 86% quantitative yield.

[0170] [Physical Properties] 1 H-NMR(400MHz,d3-acetonitrile)δ(ppm):7.42(2H,d,J=8.2Hz),7.52(2H,d,J=9.2Hz) 19 F-NMR(400MHz,d3-acetonitrile)δ(ppm):36.9(1F,s)

[0171] The reaction in Example 17 is shown below.

[0172] [ka]

[0173] [Example 18] 28 mg (0.20 mmol, 1.0 eq.) of tyramine as the substrate and 1 mL of deuterated acetonitrile as the reaction solvent were placed in a 20 mL glass flask equipped with a stir bar. Next, 34 mg (0.22 mmol, 1.1 eq.) of diazabicycloundecene was added to the flask and stirred at room temperature for 10 minutes. 60 mg (0.31 mmol, 1.5 eq.) of 4-nitroimidazole monosulfonyl fluoride was then added and stirred at room temperature for 30 minutes. The resulting reaction solution was weighed and 39 mg of 1,4-bis-trifluoromethylbenzene was added as an internal standard and mixed. After filtration, 4-(2-aminoethyl)phenolsulfonyl monofluoride was quantified by NMR analysis, confirming that 28 mg of the corresponding phenol sulfonyl fluoride was produced in a quantitative yield of 63%.

[0174] [Physical Properties] 1 H-NMR(400MHz,d3-acetonitrile)δ(ppm):2.80(2H,t,J=7.1Hz),3.25~3.30(2H,m),7.30(2H,d,J=9.8Hz),7.38(2H,d,J=8.9Hz) 19 F-NMR(400MHz,d3-acetonitrile)δ(ppm):36.4(1F,s)

[0175] The reaction in Example 18 is shown below.

[0176] [ka]

[0177] [Example 19] 23 mg (0.21 mmol, 1.0 eq.) of p-cresol as the substrate and 1 mL of deuterated acetonitrile as the reaction solvent were placed in a 20 mL glass flask equipped with a stir bar. Next, 35 mg (0.23 mmol, 1.1 eq.) of diazabicycloundecene was added to the flask and stirred at room temperature for 10 minutes. 61 mg (0.31 mmol, 1.5 eq.) of 4-nitroimidazole monosulfonyl fluoride was then added and stirred at room temperature for 30 minutes. The resulting reaction solution was weighed and 37 mg of 1,4-bis-trifluoromethylbenzene was added as an internal standard and mixed. After filtration, 4-methylphenolsulfonyl monofluoride was quantified by NMR analysis, confirming that 34 mg of the corresponding phenol sulfonyl fluoride was produced in a quantitative yield of 86%.

[0178] [Physical Properties] 1 H-NMR(400MHz,d3-acetonitrile)δ(ppm):2.33(3H,s),7.23(2H,d,J=3.4Hz),7.84(2H,d,J=1.0Hz) 19 F-NMR(400MHz,d3-acetonitrile)δ(ppm):36.3(1F,s)

[0179] The reaction in Example 19 is shown below.

[0180] [ka]

[0181] [Example 20] 22 mg (0.20 mmol, 1.0 eq.) of m-cresol as the substrate and 1 mL of deuterated acetonitrile as the reaction solvent were placed in a 20 mL glass flask equipped with a stir bar. Next, 34 mg (0.22 mmol, 1.1 eq.) of diazabicycloundecene was added to the flask and stirred at room temperature for 10 minutes. 61 mg (0.34 mmol, 1.5 eq.) of 4-nitroimidazole monosulfonyl fluoride was then added and stirred at room temperature for 30 minutes. The resulting reaction solution was weighed and 54 mg of 1,4-bis-trifluoromethylbenzene was added as an internal standard and mixed. After filtration, 3-methylphenolsulfonyl monofluoride was quantified by NMR analysis, confirming that 37 mg of the corresponding phenol sulfonyl fluoride was produced in a quantitative yield of 97%.

[0182] [Physical Properties] 1 H-NMR(400MHz,d3-acetonitrile)δ(ppm):2.36(3H,s),7.19~7.40(4H,m) 19 F-NMR(400MHz,d3-acetonitrile)δ(ppm):36.7(1F,s)

[0183] The reaction in Example 20 is shown below.

[0184] [ka]

[0185] [Example 21] 22 mg (0.20 mmol, 1.0 eq.) of o-cresol as the substrate and 1 mL of deuterated acetonitrile as the reaction solvent were placed in a 20 mL glass flask equipped with a stir bar. Next, 34 mg (0.22 mmol, 1.1 eq.) of diazabicycloundecene was added to the flask and stirred at room temperature for 10 minutes. 60 mg (0.34 mmol, 1.5 eq.) of 4-nitroimidazole monosulfonyl fluoride was then added and stirred at room temperature for 30 minutes. The resulting reaction solution was weighed and 32 mg of 1,4-bis-trifluoromethylbenzene was added as an internal standard and mixed. After filtration, 2-methylphenolsulfonyl monofluoride was quantified by NMR analysis, confirming that 37 mg of the corresponding phenol sulfonyl fluoride was produced in 100% quantitative yield.

[0186] [Physical Properties] 1 H-NMR(400MHz,d3-acetonitrile)δ(ppm):2.33(3H,s),7.31~7.38(3H,m),7.84(1H,d,J=1.0Hz) 19 F-NMR(400MHz,d3-acetonitrile)δ(ppm):38.3(1F,s)

[0187] The reaction in Example 21 is shown below.

[0188] [ka]

[0189] The NMR yield results for Examples 15-21 are summarized in Table 2 below. [Table 2]

[0190] (Study on synthesis conditions for 4-nitroimidazole SO2F) [Example 22] 3.18 g (28.1 mmol, 1.0 eq.) of 4-nitroimidazole as the substrate, 7.46 g (70.3 mmol, 2.5 eq.) of sodium carbonate, and 28 mL of acetonitrile as the reaction solvent were placed in a 300 mL stainless steel (SUS) pressure vessel. Subsequently, 7.18 g (70.3 mmol, 2.5 eq.) of sulfuryl fluoride gas was slowly introduced from a cylinder, and the mixture was stirred overnight at room temperature. The reaction mixture was filtered through Celite while rinsing with 56 mL of acetonitrile, and the filtrate was concentrated under reduced pressure. The crude product obtained by concentration was purified by silica gel column chromatography, and the solution containing the target product was concentrated to obtain 3.51 g of 4-nitroimidazole-1-sulfonyl fluoride in 64% isolation yield.

[0191] [Physical Properties] 1 H-NMR(400MHz,d6-acetone)δ(ppm):8.63(1H,d,J=1.6Hz),8.99(1H,d,J=1.6Hz) 19 F-NMR(400MHz,d6-acetone)δ(ppm):59.2(1F,s)

[0192] The reaction in Example 22 is shown below.

[0193] [ka]

[0194] [Example 23] 1.02 g (9.02 mmol, 1.0 eq.) of 4-nitroimidazole as the substrate, 2.39 g (22.6 mmol, 2.5 eq.) of sodium carbonate, and 9 mL of acetone as the reaction solvent were placed in a 200 mL stainless steel (SUS) pressure vessel. 2.30 g (22.6 mmol, 2.5 eq.) of sulfuryl fluoride gas was then slowly added from a cylinder, and the mixture was stirred overnight at room temperature. The reaction mixture was filtered through Celite while rinsing with 18 mL of acetone, and the filtrate was concentrated under reduced pressure. The crude product obtained by concentration was purified by silica gel column chromatography, and the solution containing the target product was concentrated to obtain 1.76 g of 4-nitroimidazole-1-sulfonyl fluoride in 74% isolation yield.

[0195] The reaction in Example 23 is shown below.

[0196] [ka]

[0197] Examples 22-23 are summarized in Table 3 below. [Table 3]

[0198] (Considerations for the SO2F conversion of phenols using 4-nitroimidazole SO2F) [Example 24] 109 mg (1.00 mmol, 1.0 eq.) of 4-aminophenol as the substrate was placed in a 30 mL eggplant-shaped flask equipped with a stir bar. Next, 215 mg (1.10 mmol, 1.1 eq.) of 4-nitroimidazole-1-sulfonyl fluoride, 5 mL of acetonitrile, and 167 mg (1.10 mmol, 1.1 eq.) of DBU were added to the reactor and stirred at room temperature (25 °C) for 2 hours to obtain a reaction solution. 1,4-bis(trifluoromethyl)benzene was added as an internal standard to the reaction solution, and NMR analysis was performed to quantify 4-aminophenol sulfonyl monofluoride. The NMR yield confirmed the production of 159 mg of the corresponding phenol sulfonyl fluoride in 83% quantitative yield.

[0199] [Physical Properties] 1 H-NMR(400MHz,d6-acetone)δ(ppm):6.66(2H,d,J=9.2Hz),7.09(2H,d,J=9.1Hz) 19 F-NMR(400MHz,d6-acetone)δ(ppm):34.8(1F,s)

[0200] The reaction in Example 24 is shown below.

[0201] [ka]

[0202] [Example 25] 109 mg (1.00 mmol, 1.0 eq.) of 4-aminophenol as the substrate was placed in a 30 mL eggplant-shaped flask equipped with a stir bar. Next, 215 mg (1.10 mmol, 1.1 eq.) of 4-nitroimidazole-1-sulfonyl fluoride, 5 mL of dichloromethane, and 167 mg (1.10 mmol, 1.1 eq.) of DBU were added to the reactor and stirred at room temperature (25 °C) for 2 hours to obtain a reaction solution. 1,4-bis(trifluoromethyl)benzene was added as an internal standard to the reaction solution, and NMR analysis was performed to quantify 4-aminophenolsulfonyl monofluoride. The NMR yield confirmed the production of 171 mg of the corresponding phenol sulfonyl fluoride in 83% quantitative yield.

[0203] The reaction in Example 25 is shown below.

[0204] [ka]

[0205] [Example 26] 109 mg (1.00 mmol, 1.0 eq.) of 4-aminophenol as the substrate was placed in a 30 mL eggplant-shaped flask equipped with a stir bar. Next, 215 mg (1.10 mmol, 1.1 eq.) of 4-nitroimidazole-1-sulfonyl fluoride, 5 mL of dichloromethane, and 30 mg (0.20 mmol, 0.2 eq.) of DBU were added to the reactor and stirred at room temperature (25 °C) for 2 hours to obtain a reaction solution. 1,4-bis(trifluoromethyl)benzene was added to the reaction solution as an internal standard, and NMR analysis was performed to quantify 4-aminophenolsulfonyl monofluoride. The NMR yield confirmed the production of 186 mg of the corresponding phenol sulfonyl fluoride in 97% quantitative yield.

[0206] The reaction in Example 26 is shown below.

[0207] [ka]

[0208] [Example 27] 109 mg (1.00 mmol, 1.0 eq.) of 4-aminophenol as the substrate was placed in a 30 mL eggplant-shaped flask equipped with a stir bar. Next, 215 mg (1.10 mmol, 1.1 eq.) of 4-nitroimidazole-1-sulfonyl fluoride, 5 mL of dichloromethane, and 15 mg (0.10 mmol, 0.1 eq.) of DBU were added to the reactor and stirred at room temperature (25 °C) for 2 hours to obtain a reaction solution. 1,4-Bis(trifluoromethyl)benzene was added as an internal standard to the reaction solution, and NMR analysis was performed to quantify 4-aminophenolsulfonyl monofluoride. The NMR yield confirmed the production of 152 mg of the corresponding phenol sulfonyl fluoride in 79% quantitative yield.

[0209] The reaction in Example 27 is shown below.

[0210] [ka]

[0211] [Example 28] 109 mg (1.00 mmol, 1.0 eq.) of 4-aminophenol as the substrate was placed in a 30 mL eggplant-shaped flask equipped with a stir bar. 215 mg (1.10 mmol, 1.1 eq.) of 4-nitroimidazole-1-sulfonyl fluoride, 5 mL of dichloromethane, and 20 mg (0.20 mmol, 0.2 eq.) of triethylamine were then added to the reactor and stirred at room temperature (25 °C) for 2 hours to obtain a reaction solution. 1,4-bis(trifluoromethyl)benzene was added to the reaction solution as an internal standard, and NMR analysis was performed to quantify 4-aminophenolsulfonyl monofluoride. The NMR yield confirmed the production of 134 mg of the corresponding phenol sulfonyl fluoride in 70% quantitative yield.

[0212] The reaction in Example 28 is shown below.

[0213] [ka]

[0214] [Example 29] 109 mg (1.00 mmol, 1.0 eq.) of 4-aminophenol as the substrate was placed in a 30 mL eggplant-shaped flask equipped with a stir bar. Next, 215 mg (1.10 mmol, 1.1 eq.) of 4-nitroimidazole-1-sulfonyl fluoride, 5 mL of dichloromethane, and 26 mg (0.20 mmol, 0.2 eq.) of N,N-diisopropylethylamine were added to the reactor and stirred at room temperature (25 °C) for 2 hours to obtain a reaction solution. 1,4-Bis(trifluoromethyl)benzene was added as an internal standard to the reaction solution, and NMR analysis was performed to quantify 4-aminophenolsulfonyl monofluoride. The NMR yield confirmed the production of 128 mg of the corresponding phenol sulfonyl fluoride in 67% quantitative yield.

[0215] The reaction in Example 29 is shown below.

[0216] [ka]

[0217] [Example 30] 109 mg (1.00 mmol, 1.0 eq.) of 4-aminophenol as the substrate was placed in a 30 mL eggplant-shaped flask equipped with a stir bar. Next, 215 mg (1.10 mmol, 1.1 eq.) of 4-nitroimidazole-1-sulfonyl fluoride, 5 mL of acetonitrile, and 30 mg (0.20 mmol, 0.2 eq.) of DBU were added to the reactor and stirred at room temperature (25 °C) for 2 hours to obtain a reaction solution. 1,4-bis(trifluoromethyl)benzene was added as an internal standard to the reaction solution, and NMR analysis was performed to quantify 4-aminophenolsulfonyl monofluoride. 76 mg of the corresponding phenol sulfonyl fluoride was confirmed to be produced in a quantitative yield of 40%.

[0218] The reaction in Example 30 is shown below.

[0219] [ka]

[0220] [Example 31] 109 mg (1.00 mmol, 1.0 eq.) of 4-aminophenol as the substrate was placed in a 30 mL eggplant-shaped flask equipped with a stir bar. Next, a mixture consisting of 215 mg (1.10 mmol, 1.1 eq.) of 4-nitroimidazole-1-sulfonyl fluoride and 5 mL of tetrahydrofuran, as well as 167 mg (1.1 mmol, 1.1 eq.) of DBU, was added to the reactor and stirred at room temperature (25 °C) for 2 hours to obtain a reaction solution. 1,4-bis(trifluoromethyl)benzene was added to the reaction solution as an internal standard, and NMR analysis was performed to quantify 4-aminophenolsulfonyl monofluoride. The NMR yield confirmed the production of 84 mg of the corresponding phenol sulfonyl fluoride in 44% quantitative yield.

[0221] The reaction in Example 31 is shown below.

[0222] [ka]

[0223] [Example 32] 109 mg (1.00 mmol, 1.0 eq.) of 4-aminophenol as the substrate was placed in a 30 mL eggplant-shaped flask equipped with a stir bar. Next, 215 mg (1.10 mmol, 1.1 eq.) of 4-nitroimidazole-1-sulfonyl fluoride, 5 mL of chloroform, and 167 mg (1.1 mmol, 1.1 eq.) of DBU were added to the reactor and stirred at room temperature (25 °C) for 2 hours to obtain a reaction solution. 1,4-bis(trifluoromethyl)benzene was added to the reaction solution as an internal standard, and NMR analysis was performed to quantify 4-aminophenolsulfonyl monofluoride. The NMR yield confirmed the production of 65 mg of the corresponding phenol sulfonyl fluoride in a quantitative yield of 34%.

[0224] The reaction in Example 32 is shown below.

[0225] [ka] Examples 24-32 are summarized in Table 4 below. [Table 4] [Industrial Applicability]

[0226] The monofluorosulfonylating agent composition of the present disclosure can be used as a monofluorosulfonylating agent composition in the development of pharmaceuticals and materials.

[0227] Although the present disclosure has been described in detail and with reference to specific embodiments, it will be apparent to those skilled in the art that various changes and modifications can be made without departing from the spirit and scope of the disclosure.

Claims

1. The compound includes a compound represented by the following general formula (1): Monofluorosulfonylating agent composition. 【Chemistry 1】 In general formula (1), X １ is a nitrogen atom or C(R １ ) and X ２ is a nitrogen atom or C(R ２ ) and Y １ is a nitrogen atom or C(R ３ ) and Y ２ is a nitrogen atom or C(R ４ ) and R １ ~R ４ are each independently a hydrogen atom or a monovalent or divalent substituent, R １ ~R ４ two adjacent substituents are divalent substituents, and they may be bonded to each other to form a ring, and the ring is not bound to a monovalent substituent R ５ and n is an integer from 1 to 3, R １ R when there are multiple １ may be the same or different, R ２ R when there are multiple ２ may be the same or different, R ５ R when there are multiple ５ may be the same or different, R １ ~R ５ At least one of the following is present as a monovalent substituent, and p of the monovalent substituents are electron-withdrawing groups represented by EWG, where p is an integer of 1 or more.

2. The following general formula (2a): 【Chemistry 2】 (In general formula (2a), X １１ is a nitrogen atom or C(R １１ ) and X １２ is a nitrogen atom or C(R １２ ) and Y １１ is a nitrogen atom or C(R １３ ) and Y １２ is a nitrogen atom or C(R １４ ) and R １１ ~R １４ are each independently a hydrogen atom or a monovalent substituent, R １１ ~R １４ present as a monovalent substituent, and q of the monovalent substituents are electron-withdrawing groups represented by EWG, where q is an integer of 1 to 4.) and / or a compound represented by the following general formula (2b): 【Transformation 3】 (In general formula (2b), X ２１ is a nitrogen atom or C(R ２１ ) and X ２２ is a nitrogen atom or C(R ２２ ) and X ２３ is a nitrogen atom or C(R ２３ ) and X ２４ is a nitrogen atom or C(R ２４ ) and Y ２１ is a nitrogen atom or C(R ２５ ) and Y ２２ is a nitrogen atom or C(R ２６ ) and R ２１ ~R ２６ are each independently a hydrogen atom or a monovalent or divalent substituent, R ２１ ~R ２６ two adjacent substituents are divalent substituents, and they may be bonded to each other to form a ring, and the ring is not bound to a monovalent substituent R ２７ and R ２７ R when there are multiple ２７ may be the same or different, R ２１ ~R ２７ present as a monovalent substituent, and r of the monovalent substituents are electron-withdrawing groups represented by EWG, where r is an integer of 1 or more. Monofluorosulfonylating agent composition.

3. In the general formula (2a), X １１ is C(R １１ ) and X １２ is C(R １２ ) and Y １１ is C(R １３ ) and Y １２ is a nitrogen atom, and R １１ , R １２ are each independently a hydrogen atom, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, or an electron-withdrawing group represented by EWG, and R １１ , R １２ At least one of the groups is an electron-withdrawing group represented by EWG, and R １３ is a hydrogen atom, a methyl group, an ethyl group, an n-propyl group, or an isopropyl group, In the general formula (2b), X ２１ is C(R ２１ ) and X ２２ is C(R ２２ ) and X ２３ is C(R ２３ ) and X ２４ is C(R ２４ ) and Y ２１ is a nitrogen atom or C(R ２５ ) and Y ２２ is a nitrogen atom or C(R ２６ ) and Y ２１ , Y ２２ At least one of R is a nitrogen atom, ２２ , R ２３ one of which is an electron-withdrawing group represented by EWG, and the other is a hydrogen atom, a methyl group, an ethyl group, an n-propyl group, or an isopropyl group, and R ２１ , R ２４ , R ２５ , R ２６ The monofluorosulfonylation agent composition according to claim 2, wherein each independently represents a hydrogen atom, a methyl group, an ethyl group, an n-propyl group, or an isopropyl group.

4. The monofluorosulfonylation agent composition according to any one of claims 1 to 3, wherein the electron-withdrawing group is a nitro group, a halogen atom, a cyano group, a carboxyl group, a trifluoromethyl group, an alkylcarbonyloxy group, a formyl group, an alkylcarbonyl group, or an alkoxycarbonyl group.

5. The monofluorosulfonylating agent composition according to any one of claims 1 to 3, General formula (3): Ar—OH (3) (In general formula (3), Ar represents an aromatic ring group or a substituted aromatic ring group.) reacting with an aromatic hydroxyl compound represented by Method for producing monofluorosulfonyloxy compounds.

6. reacting the monofluorosulfonylating agent composition with the aromatic hydroxyl compound in the presence of a strong non-nucleophilic base; The method for producing the monofluorosulfonyloxy compound according to claim 5.

7. A compound represented by any one of the following general formulas (4a) to (4d): 【Chemistry 4】 In the general formula (4a), R represents an alkyl group having 1 to 8 carbon atoms. ２ The NO group is bonded to a carbon atom on the ring to which R is not bonded. ２ The group is attached to a carbon atom on the six-membered ring that is not attached to a nitrogen atom.

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