Method for producing phenol compound having two or more trifluoromethyl groups in same ring, and phenol compound having two or more trifluoromethyl groups in same ring

Abstract

To provide a method for efficiently producing a phenol compound having two or more trifluoromethyl groups in the same ring, the phenol compound being useful for functional materials including electronic materials, the electrical and electronic field, and photosensitive resin compositions, and also as a raw material for pharmaceuticals and agrochemicals.SOLUTION: The present invention provides a method for producing a phenol compound having two or more trifluoromethyl groups in the same ring, characterized in that two or more trifluoromethyl groups are introduced into the same ring by reacting a phenol compound whose aromatic ring consists only of carbon atoms with trifluoroiodomethane under light irradiation in the presence of a base. The present invention also provides a phenol compound having two or more trifluoromethyl groups in the same ring.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a method for producing a phenolic compound having two or more trifluoromethyl groups in an aromatic ring having a phenol structure, and to a phenolic compound having two or more trifluoromethyl groups in the ring. [Background technology]

[0002] Phenolic compounds having a trifluoromethyl group are used in various industrial fields due to their excellent heat resistance, durability, mechanical properties, electrical properties, etc. For example, phenolic compounds having a trifluoromethyl group are known to be useful as electronic materials such as photoresists for semiconductor manufacturing, electrical and electronic fields such as IC encapsulation materials, functional materials such as photosensitive resin compositions, and raw materials for synthesizing pharmaceuticals and pesticides. Non-Patent Documents 1 and 2 describe methods for synthesizing 2,6-bis(trifluoromethyl)-4-t-butylphenol, a phenol compound having two trifluoromethyl groups. [Prior art documents] [Non-patent literature]

[0003] [Non-Patent Document 1] Umemoto, T. et al., Bulletin of the Chemical Society of Japan, (1986), 59, 447-452 [Non-patent document 2] Antonio Toni et al., Journal of Organic Chemistry (2008), 73, 7678-7685 Summary of the Invention [Problem to be solved by the invention]

[0004] In Non-Patent Document 1, a phenol compound having a trifluoromethyl group is synthesized, and Table 1 shows that the yield of 2-trifluoromethyl-4-t-butylphenol is 65% and the yield of 2,6-bis(trifluoromethyl)-4-t-butylphenol is 17%, which means that the yield of the phenol compound having two trifluoromethyl groups is less than half of the yield of the phenol compound having one trifluoromethyl group.

[0005] Non-Patent Document 2 describes the synthesis of phenolic compounds having a trifluoromethyl group, and Table 2 shows the results of introducing a trifluoromethyl group from various phenolic compounds. As in Non-Patent Document 1, the results show that the yield of phenolic compounds having two trifluoromethyl groups is less than half that of phenolic compounds having one trifluoromethyl group.

[0006] Thus, in a reaction for introducing a trifluoromethyl group into a phenol compound, it has been desired to efficiently obtain a phenol compound having two or more trifluoromethyl groups in the same ring in good yield while suppressing the production of a phenol compound having one trifluoromethyl group.

[0007] In the above-mentioned background art, phenolic compounds having only one trifluoromethyl group are obtained in greater quantities than phenolic compounds having two or more trifluoromethyl groups in the same ring, and it is difficult to efficiently obtain phenolic compounds having two or more trifluoromethyl groups. In addition, there are problems in that N-trifluoromethyl-N-nitrosotrifluoromethanesulfonamide and Togni's reagent, which are used as sources for introducing trifluoromethyl groups, are relatively expensive. Therefore, an object of the present invention is to provide an industrial process for producing a phenolic compound having two or more trifluoromethyl groups in the same ring, and a phenolic compound having two or more trifluoromethyl groups in the same ring. [Means for solving the problem]

[0008] As a result of extensive research, the present inventors have found that by irradiating trifluoroiodomethane in a solvent with light in the presence of a photosensitizer and a base and reacting it with a phenolic compound, it is possible to efficiently produce a phenolic compound having two or more trifluoromethyl groups in the same ring, in which the content of the phenolic compound having only one trifluoromethyl group in the same ring is lower than the content of aromatic compounds having two or more trifluoromethyl groups in the same ring, and have thus completed the present invention. The term "phenol compound having two or more trifluoromethyl groups in the same ring" refers to a compound having one aromatic ring with a hydroxy group, such as the compound represented by the following general formula (3), in which two or more trifluoromethyl groups are bonded as substituents to the aromatic ring; or a compound having two aromatic rings with a hydroxy group, such as the compound represented by the following general formula (4), in which two or more trifluoromethyl groups are bonded as substituents to each of the aromatic rings.

[0009] That is, the present invention relates to the following gist. [1] The following general formula (1) [ka] (In formula (1), R represents a hydrogen atom, an alkyl group having 1 to 15 carbon atoms, an alkyl group having 1 to 15 carbon atoms and substituted with a halogen atom, an alkyl group substituted with an aromatic group, an aromatic group, an alkoxy group, an alkylthio group, an alkyl group having 1 to 15 carbon atoms and substituted with an alkoxy group, an alkyl group having 1 to 15 carbon atoms and substituted with an alkylthio group, a carboalkoxy group, or a (tert-butoxycarbonyl)amino group.) or The following general formula (2) [ka] (In formula (2), R 1is none (i.e., a direct bond), an ether bond, a thioether bond, an alkylidene group having 1 to 15 carbon atoms substituted with an alkoxy group, an alkylidene group having 1 to 15 carbon atoms substituted with an alkylthio group, an alkylidene group having 1 to 15 carbon atoms substituted with a carboalkoxy group, an alkylidene group having 1 to 15 carbon atoms, an alkylidene group substituted with an aromatic group, an alkylidene group having 1 to 15 carbon atoms substituted with a halogen atom, a phenylene group, X 1 group, or X 2 represents the group: where X 1 is the following formula (2-1), and X 2 is the following formula (2-2), in which Z represents the bonding position to the aromatic ring. [ka] [ka] ) a phenol compound represented by the formula (I) is irradiated with light in the presence of a base to react with trifluoroiodomethane; The following general formula (3) [ka] (In formula (3), R is the same as in formula (1) above.) or The following general formula (4) [ka] (In formula (4), R 1 is the same as the above formula (2). A method for producing a phenol compound having two or more trifluoromethyl groups in the same ring, represented by the formula: [2] The method according to item [1], characterized in that the compound is reacted with trifluoroiodomethane by irradiating the compound with light in the presence of a photosensitizer. [3] The method according to item [2], wherein the photosensitizer is 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene or riboflavin. [4] The method according to any one of items [1] to [3], wherein the base is cesium carbonate or lithium carbonate. [5] The method according to any one of items [1] to [3], wherein the photosensitizer is 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene or riboflavin, and the base is cesium carbonate or lithium carbonate. [6] A phenol compound having two, four, or six trifluoromethyl groups, represented by any one of the following formulas (5) to (20): [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [Effects of the Invention]

[0010] According to the present invention, there are provided an industrial production method for phenolic compounds having two or more trifluoromethyl groups in an aromatic ring having a phenol structure, which are useful compounds as raw materials for electronic materials, electrical and electronic fields, functional materials, pharmaceuticals, and agricultural chemicals, and the phenolic compounds having two or more trifluoromethyl groups in the same ring. DETAILED DESCRIPTION OF THE INVENTION

[0011] Hereinafter, an industrial production method for a phenol compound having two or more trifluoromethyl groups in the same ring, and a phenol compound having two or more trifluoromethyl groups in the same ring according to one embodiment of the present disclosure will be described in detail.

[0012] The phenol compound used to obtain the phenol compound having two or more trifluoromethyl groups in the same ring obtained by one embodiment of the present invention preferably includes a compound represented by the following general formula (1) or the following general formula (2).

[0013] [ka] (In formula (1), R represents a hydrogen atom, an alkyl group having 1 to 15 carbon atoms, an alkyl group having 1 to 15 carbon atoms and substituted with a halogen atom, an alkyl group substituted with an aromatic group, an aromatic group, an alkoxy group, an alkylthio group, an alkyl group having 1 to 15 carbon atoms and substituted with an alkoxy group, an alkyl group having 1 to 15 carbon atoms and substituted with an alkylthio group, a carboalkoxy group, or a (tert-butoxycarbonyl)amino group.) [ka] (In formula (2), R 1 is none (i.e., a direct bond), an ether bond, a thioether bond, an alkylidene group having 1 to 15 carbon atoms substituted with an alkoxy group, an alkylidene group having 1 to 15 carbon atoms substituted with an alkylthio group, an alkylidene group having 1 to 15 carbon atoms substituted with a carboalkoxy group, an alkylidene group having 1 to 15 carbon atoms, an alkylidene group substituted with an aromatic group, an alkylidene group having 1 to 15 carbon atoms substituted with a halogen atom, a phenylene group, X 1 group, or X 2 represents the group: where X 1 is the following formula (2-1), and X 2 is the following formula (2-2), in which Z represents the bonding position to the aromatic ring. [ka] [ka] )

[0014] The "alkyl group" that may be included in R of the phenol compound represented by the general formula (1) means a monovalent functional group generated by removing one hydrogen atom from an alkane. The alkyl group may be linear, cyclic, or a combination thereof. A cyclic alkyl group is synonymous with a "cycloalkyl group." The linear group may be either linear or branched. The alkyl group is preferably linear or branched.

[0015] The alkyl group usually has 1 to 15 carbon atoms, and more preferably 1 to 8 carbon atoms. Specific examples include linear or branched alkyl groups such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, isohexyl, heptyl, 4,4-dimethylpentyl, octyl, 2,2,4-trimethylpentyl, nonyl, and decyl; cyclic alkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl; and alkyl groups having a linear or branched moiety and a cyclic moiety such as cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclohexylmethyl, and cyclohexylethyl.

[0016] The "alkyl group substituted with a halogen atom" that may be contained in R of the phenol compound represented by the general formula (1) is a functional group in which the hydrogen atoms of the "alkyl group" are substituted with any number of halogen atoms. The "halogen atom" refers to a fluorine atom, chlorine atom, bromine atom, or iodine atom. The number of halogen atoms contained in the alkyl group substituted with a halogen atom is usually 1 to 4, preferably 1 to 3, and more preferably 1 or 2.

[0017] The "alkyl group substituted with an aromatic group" which may be contained in R of the phenol compound represented by the general formula (1) is a functional group in which a hydrogen atom of the "alkyl group" is substituted with a phenyl group having one aromatic ring or an aromatic group having any number of aromatic rings. The number of aromatic groups contained in the alkyl group substituted with an aromatic group is usually 1 to 4, preferably 1 to 3, and more preferably 1 or 2. In particular, when the aromatic group is a polycyclic aromatic hydrocarbon group or a substituted polycyclic aromatic hydrocarbon group, the number is preferably 1 or 2 from the viewpoint of the steric structure that can be adopted.

[0018] R of the phenol compound represented by the general formula (1) or R of the phenol compound represented by the general formula (2) 1The term "aromatic group" as used herein means a monovalent functional group formed by replacing one hydrogen atom on an aromatic ring, and includes a phenyl group having one aromatic ring and functional groups having any number of aromatic rings. The "aromatic group" is not particularly limited, but examples thereof include aromatic hydrocarbon groups, substituted aromatic hydrocarbon groups, polycyclic aromatic hydrocarbon groups, substituted polycyclic aromatic hydrocarbon groups, heterocyclic aromatic groups, and fluorene groups. Specific examples thereof include a phenyl group, a 2-methylphenyl group, a 3-methylphenyl group, a 4-methylphenyl group, a 2-methoxyphenyl group, a 3-methoxyphenyl group, a 4-methoxyphenyl group, a 2,3-dimethylphenyl group, a 2,4-dimethylphenyl group, a 2,5-dimethylphenyl group, a 2,6-dimethylphenyl group, a 3,4-dimethylphenyl group, a 3,5-dimethylphenyl group, a 2,4,6-trimethylphenyl group, a 2,3-diisopropylphenyl group, a 2,4-diisopropylphenyl group, a 2,5-diisopropylphenyl group, a 2,6-diisopropylphenyl group, a 3,4-diisopropylphenyl group, a 3,5-diisopropylphenyl group, a 2-ethylphenyl group, a 3-ethylphenyl group, a 4-ethylphenyl group, a 2-isopropylphenyl group, a 3-isopropylphenyl group, a 4-isopropylphenyl group, a 2-tert-butylphenyl group, a 3-tert-butylphenyl group, a 4-tert-butylphenyl group, a 2-trifluoromethylphenyl group, a 3-trifluoromethyl ...tert-butylphenyl group, a 4-tert-butylphenyl group, a 2-trifluoromethylphenyl group, a 3-trifluoromethylphenyl group, a 2-isopropylphenyl group, a 3-tert-butylphenyl group, a 4-tert-butylphenyl group, a 2-trifluoromethylphenyl group, a 3-trifluoromethylphenyl group, a 2-isopropylphenyl group, a 3-tert-butylphenyl group, a Examples thereof include a methylphenyl group, a 4-trifluoromethylphenyl group, a 2,3-dichlorophenyl group, a 2,4-dichlorophenyl group, a 2,5-dichlorophenyl group, a 2,6-dichlorophenyl group, a 3,4-dichlorophenyl group, a 3,5-dichlorophenyl group, a 2-chlorophenyl group, a 3-chlorophenyl group, a 4-chlorophenyl group, a 2-fluorophenyl group, a 3-fluorophenyl group, a 4-fluorophenyl group, a 2-bromophenyl group, a 3-bromophenyl group, a 4-bromophenyl group, a 1-naphthyl group, a 2-naphthyl group, a 2-thienyl group, a 3-thienyl group, a 2-phenylphenyl group, a 3-phenylphenyl group, a 4-phenylphenyl group, a 2-carboxymethylphenyl group, a 3-carboxymethylphenyl group, a 4-carboxymethylphenyl group, a 2-carboxyethylphenyl group, a 3-carboxyethylphenyl group, a 4-carboxyethylphenyl group, a 4-(carboxy3-bromopropyl)phenyl group, and a 4-(carboxy(4-bromophenyl)methyl)phenyl group.

[0019] R of the phenol compound represented by the general formula (1) or R of the phenol compound represented by the general formula (2) 1 The "alkoxy group" that may be included in the above refers to a group in which a hydrocarbon group is bonded via an ether bond, such as a methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, or benzyloxy group, and this hydrocarbon group may or may not have a substituent. The number of carbon atoms in the alkoxy group is not particularly limited, but is preferably in the range of 1 to 15.

[0020] R of the phenol compound represented by the general formula (1) or R of the phenol compound represented by the general formula (2) 1 The "alkylthio group" sometimes included in refers to a group in which a hydrocarbon group is bonded via a thioether bond, such as a methylthio group, an ethylthio group, an n-propylthio group, an isopropylthio group, an n-butylthio group, or a benzylthio group, and this hydrocarbon group may or may not have a substituent. The number of carbon atoms in the alkylthio group is not particularly limited, but is preferably in the range of 1 to 15.

[0021] The "alkoxy-substituted alkyl group" that may be contained in R of the phenol compound represented by the general formula (1) is a functional group in which a hydrogen atom of the "alkyl group" is substituted with an alkoxy group. The number of alkoxy groups contained in the alkoxy-substituted alkyl group is usually 1 to 4, preferably 1 to 3, and more preferably 1 or 2.

[0022] The "alkyl group having 1 to 15 carbon atoms substituted with an alkylthio group" which may be contained in R of the phenol compound represented by the general formula (1) is a functional group in which a hydrogen atom of the "alkyl group" is substituted with an alkylthio group. The number of alkylthio groups contained in the alkyl group substituted with an alkylthio group is usually 1 to 4, preferably 1 to 3, and more preferably 1 or 2.

[0023] R of the phenol compound represented by the general formula (1) or R of the phenol compound represented by the general formula (2) 1 Examples of the "carboalkoxy group" that may be included in include a carbomethoxy group, a carboethoxy group, a carboisopropoxy group, a carbobenzyloxy group, and the like.

[0024] R of the phenol compound represented by the general formula (2) 1 The "alkylidene group" that may be included in the above means a divalent functional group formed by removing two hydrogen atoms from an alkane. The alkylidene group may be linear, cyclic, or a combination thereof. A cyclic alkylidene group is synonymous with a "cycloalkylidene group." The linear alkylidene group may be linear or branched.

[0025] The alkylidene group usually has 1 to 15 carbon atoms, and more preferably 1 to 8 carbon atoms. Specific examples include straight-chain or branched-chain alkylidene groups such as a methylidene group (synonymous with a methylene group), an ethylidene group, a propylidene group, an isopropylidene group, an n-butylidene group, an isobutylidene group, a pentylidene group, a hexylidene group, an isohexylidene group, a heptylidene group, a 4,4-dimethylpentylidene group, an octylidene group, a 2,2,4-trimethylpentylidene group, and a nonylidene group; cyclic alkylidene groups such as a cyclopropylidene group, a cyclobutylidene group, a cyclopentylidene group, a cyclohexylidene group, a cycloheptylidene group, and a cyclooctylidene group; and alkylidene groups having a straight-chain or branched-chain moiety and a cyclic moiety such as a cyclopentylmethylidene group, a cyclopentylethylidene group, a cyclopentylpropylidene group, a cyclohexylmethylidene group, and a cyclohexylethylidene group.

[0026] R of the phenol compound represented by the general formula (2) 1The "alkylidene group substituted with a halogen atom" that may be included in the above is a functional group in which the hydrogen atoms of the "alkylidene group" are substituted with any number of halogen atoms. The "halogen atom" means a fluorine atom, chlorine atom, bromine atom, or iodine atom. The number of halogen atoms contained in the alkyl group substituted with a halogen atom is usually 1 to 8, and preferably 1 to 6.

[0027] R of the phenol compound represented by the general formula (2) 1 The "alkylidene group substituted with an aromatic group" that may be included in the above is a functional group in which the hydrogen atom of the "alkylidene group" is substituted with a phenyl group having one aromatic ring or an aromatic group having any number of aromatic rings. The number of aromatic groups contained in the alkyl group substituted with an aromatic group is usually 1 to 4, preferably 1 to 3, and more preferably 1 or 2. In particular, when the aromatic group is a polycyclic aromatic hydrocarbon group or a substituted polycyclic aromatic hydrocarbon group, the number is preferably 1 or 2 from the viewpoint of the steric structure that can be adopted.

[0028] R of the phenol compound represented by the general formula (2) 1 The "alkylidene group having 1 to 15 carbon atoms substituted with an alkoxy group" that may be included in the above is a functional group in which a hydrogen atom of the "alkylidene group" is substituted with an alkoxy group. The number of alkoxy groups contained in the alkylidene group substituted with an alkoxy group is usually 1 to 4, preferably 1 to 3, and more preferably 1 or 2.

[0029] In addition, R of the phenol compound represented by the general formula (2) 1 The "alkylidene group having 1 to 15 carbon atoms substituted with an alkylthio group" which may be included in the above is a functional group in which a hydrogen atom of the "alkylidene group" is substituted with an alkylthio group. The number of alkylthio groups contained in the alkylidene group substituted with an alkylthio group is usually 1 to 4, preferably 1 to 3, and more preferably 1 or 2.

[0030] In addition, R of the phenol compound represented by the general formula (2) 1The "alkylidene group having 1 to 15 carbon atoms substituted with a carboalkoxy group" that may be included in the above is a functional group in which a hydrogen atom of the "alkylidene group" is substituted with a carboalkoxy group. The number of carboalkoxy groups contained in the alkylidene group substituted with a carboalkoxy group is usually 1 to 4, preferably 1 to 3, and more preferably 1 or 2.

[0031] R of the phenol compound represented by the general formula (2) 1 However, "none (i.e. direct bond)" means R 1 The term "ether bond" refers to a structure in which the aromatic rings on both sides of R 1 is oxygen (O), forming a "-O-" bond, and "thioether bond" R 1 is sulfur (S), and the bond is "-S-".

[0032] R of the phenol compound represented by the general formula (2) 1 However, "formula (2-1)" refers to a phenol compound represented by the following formula (21). [ka] R of the phenol compound represented by the general formula (2) 1 However, "formula (2-2)" refers to a phenol compound represented by the following formula (22). [ka]

[0033] In one embodiment, a photosensitizer may or may not be used in the preparation of the phenolic compounds of the present invention having two or more trifluoromethyl groups in the same ring. When a photosensitizer is used, applicable photosensitizers are not particularly limited, but examples include 4CzIPN (1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene), Ir(ppy) (tris(2-phenylpyridine)iridium(III)), 4DPAIPN (1,3-dicyano-2,4,5,6-tetrakis(N,N-diphenylamino)benzene), N-[2-(dimethylamino)ethyl]-1,8-naphthalimide, Acidred 87 (eosin Y), and riboflavin (vitamin B). Of these, 4CzIPN and riboflavin are more preferred from the standpoints of catalytic activity and availability.

[0034] When carrying out the reaction of the present invention, a method or device for irradiating light with a wavelength that covers the absorption wavelengths of the photosensitizer and trifluoroiodomethane can be used, for example, a method or device for irradiating light with a wavelength that covers all or any of the range from 300 to 550 nm can be used. Specifically, examples include methods using natural light, heat-generating light such as fluorescent light, LED, OLED (organic light emitting diode), and the like.

[0035] In one embodiment, the amount of photosensitizer applicable to the production of the phenol compound having two or more trifluoromethyl groups in the same ring of the present invention may be 0.001 molar or more relative to the phenol compound used as the raw material. 0.005 to 0.5 molar amounts are preferred. 0.02 to 0.1 molar amounts are particularly preferred. If the amount of photosensitizer is too small, the yield will be poor, and if it is too large, the cost of the photosensitizer may be high.

[0036] In one embodiment, the amount of trifluoroiodomethane applicable to the production of the phenol compound having two or more trifluoromethyl groups in the same ring of the present invention is preferably 1.5 molar times or more, more preferably 1.7 to 5.0 molar times, and particularly preferably 2.0 to 4.0 molar times, relative to the amount of the phenol compound represented by the general formula (1) used as a raw material. The amount is preferably 2.0 times by mole or more, more preferably 2.0 to 30.0 times by mole, and particularly preferably 5.0 to 20.0 times by mole relative to the phenol compound represented by the general formula (2). If the amount of trifluoroiodomethane is too small, the yield may be poor, whereas if the amount is too large, the cost of trifluoroiodomethane may be high and the yield may be poor.

[0037] In one embodiment, the base applicable to the production of the phenol compound of the present invention having two or more trifluoromethyl groups in the same ring is not particularly limited, but examples thereof include cesium carbonate, lithium carbonate, silver carbonate, potassium phosphate, potassium t-butoxide, etc. A combination of multiple bases may also be used. Cesium carbonate and lithium carbonate are particularly preferred, and cesium carbonate is more preferred.

[0038] In one embodiment, the amount of the base applicable to the production of the phenol compound having two or more trifluoromethyl groups in the same ring of the present invention is preferably 1.0 molar amount or more, more preferably 1.0 to 5.0 molar amounts, and particularly preferably 3.0 to 5.0 molar amounts, relative to the amount of the phenol compound represented by the general formula (1) used as a raw material. The amount is preferably 2.0 times by mole or more, more preferably 2.0 to 15.0 times by mole, and particularly preferably 3.0 to 10.0 times by mole relative to the phenol compound represented by the general formula (2). If the amount of base is too small, the yield may be poor, whereas if the amount is too large, the cost of the base is high and an operation to remove the remaining base is required, which may make the process complicated.

[0039] In one embodiment, the reaction atmosphere in the production of the phenol compound having two or more trifluoromethyl groups in the same ring of the present invention is preferably an inert gas atmosphere such as argon or nitrogen, taking into consideration the activity of the photosensitizer. The reaction pressure may be any of elevated pressure, atmospheric pressure, and reduced pressure.

[0040] In one embodiment, the reaction temperature and reaction time in the production of the phenol compound of the present invention having two or more trifluoromethyl groups in the same ring may be appropriately determined depending on the amount of substrate and the amount of catalyst used, and are not particularly limited. The reaction temperature and reaction time are usually 0.5 to 72 hours in the temperature range of -30°C to 120°C, preferably 1 to 48 hours in the temperature range of -10°C to 100°C, and more preferably 3 to 24 hours in the temperature range of 10°C to 80°C.

[0041] In one embodiment, the solvent used in the production of the phenol compound of the present invention having two or more trifluoromethyl groups in the same ring is preferably an organic solvent. For example, an amide solvent such as dimethylacetamide or dimethylformamide, or dimethyl sulfoxide may be used, or a combination of multiple solvents may be used.

[0042] In one embodiment, the post-reaction treatment in the production of a phenol compound having two or more trifluoromethyl groups in the same ring of the present invention can be carried out by a known method. For example, a saturated aqueous ammonium chloride solution is added at room temperature, followed by extraction with diethyl ether, and the collected organic phase is dried over anhydrous magnesium sulfate, filtered, concentrated, and further purified by silica gel column chromatography to obtain the target phenol compound having two or more trifluoromethyl groups in the same ring. [Example]

[0043] The present invention will be specifically explained below with reference to examples, but the present invention is not limited to these examples.

[0044] The following instruments were used for the analysis: 1 H-NMR (500MHz), 19 F-NMR (471 MHz): 500 MHz NMR device manufactured by JEOL Ltd.

[0045] Example 1 Synthesis of 2,6-bis(trifluoromethyl)-4-t-butylphenol A reactor equipped with a stirrer was charged with 75 mg (0.50 mmol) of 4-t-butylphenol and 19.7 mg (2.5 × 10 -2 After the gas phase was replaced with nitrogen, a solution of 196 mg (1.0 mmol) of trifluoroiodomethane in 164 mg of N,N-dimethylformamide was added. N,N-dimethylformamide was then added so that the trifluoroiodomethane concentration in dimethylformamide was 1 mol / L. The reaction was carried out with stirring at 10-40°C for 24 hours while irradiating with 450 nm light using an LED light (HepatoChem LED light for photoreactors, product name EvoluChem LED 450PF). After the reaction, aqueous ammonium chloride solution was added, and the mixture was extracted with diethyl ether. The organic layer was filtered through magnesium sulfate and concentrated to obtain the crude product. 19 The yield was calculated using benzotrifluoride as an internal standard in F-NMR and was found to be 69%. The crude product was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate) to obtain the target 2,6-bis(trifluoromethyl)-4-t-butylphenol (yield 64%). However, neither 4-t-butyl-2-trifluoromethylphenol, which has only one trifluoromethyl group, nor 4-t-butyl-6-trifluoromethylphenol was obtained.

[0046] The analytical results of the obtained 2,6-bis(trifluoromethyl)-4-t-butylphenol were as follows. 1 H-NMR (CDCl3, 500MHz) 7.68ppm(s, 2H), 5.93ppm(brs, 1H), 1.31ppm(s, 9H) 19 F-NMR(CDCl3, 471MHz)-60.75ppm(s, 6F)

[0047] Examples 2 to 22 Synthesis of 2,6-bis(trifluoromethyl)-4-t-butylphenol To a reactor equipped with a stirrer, 75 mg (0.50 mmol) of 4-t-butylphenol, a photosensitizer listed in Table 1, and a base listed in Table 1 were added in the amounts listed in Table 1. The gas phase was then replaced with nitrogen, and a solution of trifluoroiodomethane in the amount listed in Table 2 dissolved in the solvent listed in Table 2 was added. The solvent listed in Table 2 was then added so that the trifluoroiodomethane concentration in the solvent was 1 mol / L. The reaction was carried out with stirring at 10°C to 40°C for 24 hours while irradiating the mixture with light of the wavelength listed in Table 2 using an LED light (HepatoChem photoreactor LED light was used, EvoluChem LED 450PF (450 nm), EvoluChem LED 365PF (365 nm), EvoluChem LED 530PF (530 nm), or EvoluChem LED 405PF (405 nm)). After the reaction, an aqueous ammonium chloride solution was added, followed by extraction with diethyl ether. The organic layer was filtered through magnesium sulfate and concentrated to obtain a crude product, which was then purified by filtration. 19 The yield was calculated using F-NMR with benzotrifluoride as an internal standard. The crude product was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate) to obtain the target 2,6-bis(trifluoromethyl)-4-t-butylphenol. The results are shown in Tables 1 and 2.

[0048] [Table 1]

[0049] [Table 2]

[0050] Examples 23-29 Synthesis of phenolic compounds having two trifluoromethyl groups A reactor equipped with a stirrer was charged with the phenolic compound (0.50 mmol) listed in Table 3 and the photosensitizer listed in Table 3 in the amounts listed in Table 3. Then, 489 mg of cesium carbonate was added. After the gas phase was replaced with nitrogen, a solution of trifluoroiodomethane in the amount listed in Table 3 dissolved in N,N-dimethylformamide was added. N,N-dimethylformamide was then added so that the concentration of trifluoroiodomethane in N,N-dimethylformamide was 1 mol / L. The reaction was carried out at 10°C to 40°C for the time listed in Table 4 while irradiating the mixture with light from an LED light (HepatoChem photoreactor LED light: EvoluChem LED 450PF (450 nm), EvoluChem LED 365PF (365 nm), EvoluChem LED 530PF (530 nm), or EvoluChem LED 405PF (405 nm)) with light of the wavelength listed in Table 4. After the reaction, an aqueous solution of hydrochloric acid was added, and the mixture was extracted with diethyl ether. The organic layer was filtered with magnesium sulfate and concentrated to obtain a crude product. 19 The yield was calculated using F-NMR with benzotrifluoride as an internal standard. The crude product was purified by silica gel column chromatography (developing solvent: n-hexane / ethyl acetate) to obtain the desired phenol compound having two trifluoromethyl groups shown in Table 4. The results are shown in Tables 3 and 4.

[0051] [Table 3]

[0052] [Table 4]

[0053] The analytical results of the phenol compound having two trifluoromethyl groups obtained in Example 23 were as follows. 1H-NMR (CDCl3, 500MHz) 7.54ppm(s, 2H), 7.29ppm(t, J=8.2Hz, 2H), 7.21ppm(t, J=8.3Hz, 1H), 7.17ppm(d, J=8.1Hz, 2H), 5.91ppm(s, 2H), 1.68ppm(s, 6H) 19 F-NMR(CDCl3, 471MHz)-60.7ppm(s, 6F)

[0054] The analytical results of the phenol compound having two trifluoromethyl groups obtained in Example 24 were as follows. 1 H-NMR (CDCl3, 500MHz) 7.60ppm(s, 2H), 5.93ppm(brs, 1H), 2.49ppm(s, 3H) 19 F-NMR(CDCl3, 471MHz)-61.0ppm(s, 6F)

[0055] The analytical results of the phenol compound having two trifluoromethyl groups obtained in Example 25 were as follows. 1 H-NMR (CDCl3, 500MHz) 8.41ppm(s, 2H), 6.47ppm(s, 1H), 3.95ppm(s, 3H) 19 F-NMR(CDCl3, 471MHz)-61.1ppm(s, 6F)

[0056] The analytical results of the phenol compound having two trifluoromethyl groups obtained in Example 26 were as follows. 1 H-NMR (CDCl3, 500MHz) 7.52ppm(s, 2H), 5.86ppm(s, 1H), 2.55-2.49ppm(m, 1H), 1.89 -1.81ppm(m, 4H), 1.78-1.72ppm(m, 1H), 1.42-1.34ppm(m, 4H), 1.30-1.20ppm(m, 1H) 19 F-NMR(CDCl3, 471MHz)-60.7(s, 6F)

[0057] The analytical results of the phenol compound having two trifluoromethyl groups obtained in Example 27 were as follows. 1 H-NMR (CDCl3, 500MHz) 7.67ppm(s, 2H), 6.02ppm(s, 1H), 3.69ppm(s, 2H), 2.41ppm(t, J=7.3H z, 2H), 1.54ppm (sext, J=7.3Hz, 2H), 1.37ppm (sept, J=6.1Hz, 2H), 0.89ppm (t, J=6.1Hz, 3H), 19 F-NMR(CDCl3, 471MHz)-60.9ppm(s, 6F)

[0058] The analytical results of the phenol compound having two trifluoromethyl groups obtained in Example 28 were as follows. 1 H-NMR (CDCl3, 500MHz) 7.75ppm(s, 2H), 6.55ppm(s, 1H), 5.82ppm(s, 1H), 1.50ppm(s, 9H) 19 F-NMR(CDCl3, 471MHz)-60.1ppm(s, 6F)

[0059] The analytical results of the phenol compound having two trifluoromethyl groups obtained in Example 29 were as follows. 1 H-NMR (CDCl3, 500MHz) 7.69ppm (s, 2H), 6.00ppm (s, 1H), 4.46ppm (s, 2H), 3.69ppm (sept, J=6.1Hz, 1H), 1.22ppm (d, J=6.1Hz, 6H) 19 F-NMR(CDCl3, 471MHz)-60.9ppm(s, 6F)

[0060] Examples 30-38 Synthesis of phenolic compounds having four or six trifluoromethyl groups A reactor equipped with a stirrer was charged with a phenolic compound (0.50 mmol) listed in Table 5, 977 mg of cesium carbonate, and a solution of trifluoroiodomethane (1371 mg) dissolved in N,N-dimethylformamide after the gas phase was replaced with nitrogen. N,N-dimethylformamide was then added so that the concentration of trifluoroiodomethane in N,N-dimethylformamide was 1 mol / L. The reaction was carried out with stirring at 10°C to 40°C for 24 hours while irradiating with light of 450 nm wavelength using an LED light (HepatoChem's EvoluChem LED 450PF (450 nm) LED light for photoreactors). After the reaction, an aqueous hydrochloric acid solution was added, followed by extraction with diethyl ether. The organic layer was filtered through magnesium sulfate and concentrated to obtain a crude product, which was then 19 The yield was calculated using F-NMR with benzotrifluoride as an internal standard. The crude product was purified by silica gel column chromatography (developing solvent: n-hexane / ethyl acetate) to obtain the desired phenol compound having four or six trifluoromethyl groups shown in Table 5. The results are shown in Table 5.

[0061] [Table 5]

[0062] The analytical results of the phenol compound having four trifluoromethyl groups obtained in Example 30 were as follows. 1 H-NMR (CDCl3, 500MHz) 6.20ppm (brs, 2H), 7.85ppm (s, 4H) 19 F-NMR(CDCl3, 471MHz)-61.0ppm(s, 12F) 13 C-NMR (DMSO-d6, 125MHz) 120.7ppm (q, J=30.0Hz), 123.3ppm (q, J=273.0Hz), 129.6ppm (d, J=14.8Hz), 129.9ppm, 152.8ppm

[0063] The analytical results of the four trifluoromethyl group-containing phenol compounds obtained in Example 31 were as follows. 1 H-NMR (CDCl3, 500MHz) 1.70ppm(s, 6H), 6.04ppm(brs, 2H), 7.51ppm(s, 4H) 19 F-NMR(CDCl3, 471MHz)-60.8ppm(s, 12F) 13 C-NMR (DMSO-d6, 125MHz) 30.2ppm, 42.4ppm, 120.6ppm (q, J=29.3Hz), 123.7ppm (q, J=272.8Hz), 129.3ppm, 141.7ppm, 151.8ppm

[0064] The analytical results of the four trifluoromethyl group-containing phenol compounds obtained in Example 32 were as follows. 1 H-NMR (CDCl3, 500MHz) 6.11ppm (brs, 2H), 7.07ppm (d, J=7.9Hz, 4H). 7.28-7.38ppm(m, 6H), 7.53ppm(s, 4H) 19 F-NMR(CDCl3, 471MHz)-60.9ppm(s, 12F) 13 C-NMR (DMSO-d6, 125MHz) 63.0ppm, 119.8ppm (q, J=29.7Hz), 123.1ppm (q, J=271.7Hz), 127.1ppm, 128.6ppm, 130.1ppm, 132.1ppm, 137.3ppm, 144.5ppm, 151.7ppm

[0065] The analytical results of the four trifluoromethyl group-containing phenolic compounds obtained in Example 33 were as follows. 1 H-NMR (CDCl3, 500MHz) 1.54ppm (brs, 6H), 2.25ppm (brs, 4H), 6.00ppm (brs, 2H), 7.55ppm (s, 4H) 19F-NMR(CDCl3, 471MHz)-60.8ppm(s, 12F) 13 C-NMR (DMSO-d6, 125MHz) 22.2ppm, 25.2ppm, 35.7ppm, 45.0ppm, 120.4ppm (q, J=29.8Hz), 123.3ppm (q, J=273.4Hz), 129.2ppm, 139.2ppm, 151.2ppm

[0066] The analytical results of the six trifluoromethyl group-containing phenolic compounds obtained in Example 34 were as follows. 1 H-NMR (CDCl3, 500MHz) 6.44ppm (brs, 2H), 7.69ppm (s, 4H) 19 F-NMR (CDCl3, 471MHz) -61.2ppm(s, 12F), -64.1ppm(s, 6H) 13 C-NMR (DMSO-d6, 125MHz) 62.8ppm (quin, J=26.5Hz), 120.6ppm (q, J=30.5Hz), 121.7ppm, 122.7ppm (q, J=272.7Hz), 123.3ppm (q, J=287.5Hz), 131.7ppm, 155.0ppm

[0067] The analytical results of the phenol compound having four trifluoromethyl groups obtained in Example 35 were as follows. 1 H-NMR (CDCl3, 500MHz) 5.95ppm (brs, 2H), 7.37ppm (s, 4H) 19 F-NMR(CDCl3, 471MHz)-61.3ppm(s, 12F) 13 C-NMR (DMSO-d6, 125MHz) 122.1ppm (q, J=29.7Hz), 122.8ppm (q, J=273.1Hz), 148.9ppm, 149.4ppm

[0068] The analytical results of the phenol compound having four trifluoromethyl groups obtained in Example 36 were as follows. 1 H-NMR (CDCl3, 500MHz) 6.18ppm (brs, 2H), 7.72ppm (s, 4H) 19 F-NMR(CDCl3, 471MHz)-61.2ppm(s, 12F) 13 C-NMR (DMSO-d6, 125MHz) 121.8ppm (q, J=30.4Hz), 123.2ppm (q, J=273.6Hz), 125.9ppm, 134.6ppm, 153.7ppm

[0069] The analytical results of the phenol compound having four trifluoromethyl groups obtained in Example 37 were as follows. 1 H-NMR (CDCl3, 500MHz) 1.68ppm(s, 12H), 5.92ppm(brs, 2H), 7.11ppm(s, 4H), 7.52ppm(s, 4H) 19 F-NMR(CDCl3, 471MHz)-61.6ppm(s, 12F) 13 C-NMR (DMSO-d6, 125MHz) 29.9ppm, 41.8ppm, 120.0ppm (q, J=29.4Hz), 123.3ppm (q, J=272.8Hz), 126.5ppm, 128.5ppm, 142.8ppm, 146.6ppm, 150.9ppm

[0070] The analytical results of the phenol compound having four trifluoromethyl groups obtained in Example 38 were as follows. 1 H-NMR (CDCl3, 500MHz) 7.69ppm (t, J=7.3Hz, 1H), 7.73ppm (s, 4H), 7.89-7.93ppm (m, 2H), 8.14ppm (d, J=7.9Hz, 1H) 19 F-NMR(CDCl3, 471MHz)-61.1ppm(s, 12F) 13C-NMR (DMSO-d6, 125MHz) 88.8ppm, 120.6ppm (q, J=30.4Hz), 123.0ppm (q, J=274.3Hz), 124.5ppm, 124.6 ppm, 126.3ppm, 129.5ppm (d, J=4.6Hz), 130.7ppm, 131.5ppm, 135.7ppm, 149.9ppm, 154.1ppm, 168.1ppm [Industrial Applicability]

[0071] According to the present invention, a method for producing a phenolic compound having two or more trifluoromethyl groups, which is a compound useful as a raw material for electronic materials, electrical and electronic fields, functional materials, pharmaceuticals, and agricultural chemicals, and a phenolic compound having two or more trifluoromethyl groups are provided, and are therefore industrially useful.

Claims

1. The following general formula (1) 【Chemical formula 29】 (In formula (1), R represents a hydrogen atom, an alkyl group having 1 to 15 carbon atoms, an alkyl group having 1 to 15 carbon atoms and substituted with a halogen atom, an alkyl group substituted with an aromatic group, an aromatic group, an alkoxy group, an alkylthio group, an alkyl group having 1 to 15 carbon atoms and substituted with an alkoxy group, an alkyl group having 1 to 15 carbon atoms and substituted with an alkylthio group, a carboalkoxy group, or a (tert-butoxycarbonyl)amino group.) or The following general formula (2) 【Chemistry 30】 (In formula (2), R １ is none (i.e., a direct bond), an ether bond, a thioether bond, an alkylidene group having 1 to 15 carbon atoms substituted with an alkoxy group, an alkylidene group having 1 to 15 carbon atoms substituted with an alkylthio group, an alkylidene group having 1 to 15 carbon atoms substituted with a carboalkoxy group, an alkylidene group having 1 to 15 carbon atoms, an alkylidene group substituted with an aromatic group, an alkylidene group having 1 to 15 carbon atoms substituted with a halogen atom, a phenylene group, １ or X ２ represents the group: Here, X １ is the following formula (2-1), and X ２ is the following formula (2-2), in which Z represents the bonding position to the aromatic ring. 【Chemical 31】 【Chemical 32】 ） a phenol compound represented by the formula (I) is irradiated with light in the presence of a base to react with trifluoroiodomethane; The following general formula (3) 【Chemical 33】 (In formula (3), R is the same as in formula (1) above.) or The following general formula (4) 【Chemical 34】 (In formula (4), R １ is the same as the above formula (2). A method for producing a phenol compound having two or more trifluoromethyl groups in the same ring, represented by the formula:

2. 2. The method according to claim 1, wherein the compound is reacted with trifluoroiodomethane by irradiation with light in the presence of a photosensitizer.

3. 3. The method according to claim 2, wherein the photosensitizer is 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene or riboflavin.

4. The method according to any one of claims 1 to 3, wherein the base is cesium carbonate or lithium carbonate.

5. 4. The method according to claim 1, wherein the photosensitizer is 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene or riboflavin, and the base is cesium carbonate or lithium carbonate.

6. A phenol compound having two, four, or six trifluoromethyl groups, represented by any one of the following formulas (5) to (20): 【Chemistry 35】 【Chemical 36】 【Chemical 37】 【Chemical Formula 38】 【Chemical Formula 39】 【Chemistry 40】 【Chemistry 41】 【Chemistry 42】 【Chemistry 43】 【Chemical Formula 44】 【Chemistry 45】 【Chemistry 46】 【Chemistry 47】 【Chemistry 48】 【Chemistry 49】 【Chemistry 50】

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