JP2006232821A - Aromatic amines and method for producing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain an aromatic amine and to provide a method for simply and efficiently producing the same. <P>SOLUTION: An aromatic amine compound represented by general formula (4) [Ar is an aromatic group which may be substituted; n is 1 or 2] is reacted with 2-bromo-3,3,3-trifluoropropene in the presence of a palladium catalyst and a base to produce an aromatic amine represented by general formula (1) [Ar and n are as shown above; X is (1,1,1-trifluoro-2-propylidene)amino group or (1-trifluoromethylvinyl)amino group]. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to aromatic amines and a method for producing the same.

  Aromatic amines are important intermediates such as medical pesticides and electronic materials. Among them, compounds having a fluorine-containing substituent on a nitrogen atom are expected to exhibit specific physiological activities and physical properties. Among such aromatic amines, those having an N- (1,1,1-trifluoro-2-propylidene) amino group have so far been dehydrated of aniline and 1,1,1-trifluoroacetone. Only N- (1,1,1-trifluoro-2-propylidene) aniline produced by condensation is known (Non-patent Document 1). However, this production method has a problem as an industrial production method because the yield of the target product is as low as 25% after reaction at room temperature for 2 days. In addition, no application to substituted anilines or other aromatic amines has been reported so far.

Izvestiya Akademii Nauk USSR, Seriya Khimiceskaya, Vol. 3, page 450, 1965

  The object of the present invention is to develop aromatic N- (1,1,1-trifluoro-2-propylidene) amines and a simple and efficient production method thereof.

  As a result of intensive studies to solve the above problems, the present inventors have found that aromatic amines and 2-bromo-3,3,3-trifluoropropene are aromatic in the presence of a palladium catalyst and a base. It has been found that N- (1,1,1-trifluoro-2-propylidene) amines can be obtained in high yield, and the present invention has been completed.

  That is, the present invention relates to the general formula (1)

［式中、Ａｒは置換されていても良い芳香族基を示す。ｎは１または２を示す。Ｘは、式（２）

[In the formula, Ar represents an optionally substituted aromatic group. n represents 1 or 2. X is the formula (2)

で表される（１，１，１−トリフルオロ−２−プロピリデン）アミノ基、または式（２）の互変異性体である式（３）

(1,1,1-trifluoro-2-propylidene) amino group represented by the formula (3) or a tautomer of the formula (2)

で表される（１−トリフルオロメチルビニル）アミノ基を示す。ただし、ｎが２のときは、Ｘは同一または相異なっていても良い。］で表されることを特徴とする芳香族アミン類［ただし、Ｎ−（１，１，１−トリフルオロ−２−プロピリデン）アニリンを除く］である。

(1-trifluoromethylvinyl) amino group represented by the formula: However, when n is 2, X may be the same or different. ], Which is an aromatic amine [except for N- (1,1,1-trifluoro-2-propylidene) aniline].

  The present invention also provides a general formula (4)

［式中、Ａｒとｎは前記と同じ意味を示す。］で表される芳香族アミン化合物と２−ブロモ−３，３，３−トリフルオロプロペンをパラジウム触媒と塩基の存在下に反応させることを特徴とする、一般式（１）で表される芳香族アミン類の製造方法である。以下に本発明をさらに詳細に説明する。

[Wherein, Ar and n have the same meaning as described above. The aromatic amine compound represented by the general formula (1) is reacted with 2-bromo-3,3,3-trifluoropropene in the presence of a palladium catalyst and a base. It is a manufacturing method of group amines. The present invention is described in further detail below.

  As the aromatic group represented by Ar, phenyl group, naphthyl group, anthryl group, phenanthryl group, pyridyl group, pyrazyl group, pyrimidyl group, pyridazyl group, pyrazolyl group, imidazolyl group, pyrrolyl group, thienyl group, furyl group, Examples thereof include an oxazolyl group, an isooxazolyl group, a thiazolyl group, an isothiazolyl group, a quinolyl group, an isoquinolyl group, an indolyl group, an isoindolyl group, a benzoimidazolyl group, a benzothiazolyl group, a benzoxazolyl group, a benzofuryl group, and a purine group. Among these, a phenyl group, a naphthyl group, an anthryl group, a pyridyl group, a thienyl group, an indolyl group, or a benzothiazolyl group is preferable in terms of a good yield.

These aromatic groups include alkyl groups having 1 to 4 carbon atoms, alkenyl groups having 2 to 4 carbon atoms, alkynyl groups having 2 to 4 carbon atoms, alkoxy groups having 1 to 4 carbon atoms, and acyl groups having 2 to 5 carbon atoms. One or more groups may be substituted with a group, an alkoxycarbonyl group having 2 to 5 carbon atoms, an alkylamino group having 1 to 4 carbon atoms, a dialkylamino group having 1 to 4 carbon atoms, a cyano group, a hydroxyl group, or a halogen atom.
Specifically as a C1-C4 alkyl group as a substituent of an aromatic group, a methyl group, an ethyl group, a propyl group, an isopropyl group, a cyclopropyl group, a butyl group, an isobutyl group, sec-butyl group, Examples thereof include a tert-butyl group, a cyclobutyl group, and a cyclopropylmethyl group.

  In addition, one or more of these alkyl groups may be substituted with a halogen atom. Specifically, a chloromethyl group, a 2-chloroethyl group, a 3-chloropropyl group, a difluoromethyl group, a 3-fluoropropyl group, a trimethyl group, Examples thereof include a fluoromethyl group, a 2-fluoroethyl group, a 2,2,2-trifluoroethyl group, and a 2,2,2-trichloroethyl group.

  Specific examples of the alkenyl group having 2 to 4 carbon atoms as the substituent of the aromatic group include a vinyl group, a 1-methylvinyl group, a 1-propenyl group, a 2-propenyl group, a 3-butenyl group, and 2-methyl. Examples thereof include a 2-propenyl group, a 1-ethylvinyl group, a 2-butenyl group, and a 1,3-butanedienyl group.

  In addition, one or more of these alkenyl groups may be substituted with a halogen atom, and specifically, 1- (chloromethyl) vinyl group, 1- (difluoromethyl) vinyl group, 1- (trifluoromethyl) vinyl. Group, 2-chloromethyl-2-propenyl group, 2-difluoromethyl-propenyl group, 2-trifluoromethyl-2-propenyl group, 1- (2-chloroethyl) vinyl group, 1- (2-fluoroethyl) vinyl Examples include a group, 1- (2,2,2-trifluoroethyl) vinyl group, 1- (2,2,2-trichloroethyl) vinyl group, and the like.

  Specific examples of the alkynyl group having 2 to 4 carbon atoms as the substituent of the aromatic group include ethynyl group, 1-propynyl group, 2-propynyl group, 1-butynyl group, 2-butynyl group and 3-butynyl group. Etc. can be illustrated.

  One or more of these alkynyl groups may be substituted with a halogen atom, specifically, 3-chloro-1-propenyl group, 3,3-difluoro-1-propenyl group, 3,3,3-tri Fluoro-1-propenyl group, 4-chloro-1-butynyl group, 4-fluoro-1-butynyl group, 4,4-difluoro-1-butynyl group, 4,4,4-trifluoro-1-butynyl group, Examples include 4-chloro-2-butynyl group, 4,4-difluoro-2-butynyl group, 4,4,4-trifluoro-2-butynyl group and the like.

  Specific examples of the alkoxy group having 1 to 4 carbon atoms as the substituent for the aromatic group include methoxy group, ethoxy group, propoxy group, isopropyloxy group, cyclopropyloxy group, butoxy group, isobutyloxy group, sec- Examples thereof include a butyloxy group, a tert-butyloxy group, a cyclobutyloxy group, and a cyclopropylmethyloxy group.

  In addition, one or more of these alkoxy groups may be substituted with a halogen atom, specifically, a chloromethoxy group, a 2-chloroethoxy group, a 3-chloropropoxy group, a difluoromethoxy group, a 3-fluoropropoxy group, Examples thereof include a trifluoromethoxy group, a 2-fluoroethoxy group, a 2,2,2-trifluoroethoxy group, and a 2,2,2-trichloroethoxy group.

  Specific examples of the acyl group having 2 to 5 carbon atoms as the substituent of the aromatic group include an acetyl group, a propionyl group, a butyryl group, an isobutyryl group, a valeryl group, an isovaleryl group, a sec-butylcarbonyl group, and a pivaloyl group. Can be illustrated.

  In these alkylcarbonyl groups, one or more alkyl groups may be substituted with a halogen atom. Specifically, a 2-chloroethylcarbonyl group, a 3-chloropropylcarbonyl group, a difluoromethylcarbonyl group, a 3-fluoromethylcarbonyl group, Examples include a fluoropropylcarbonyl group, a trifluoromethylcarbonyl group, a 2-fluoroethylcarbonyl group, a 2,2,2-trifluoroethylcarbonyl group, or a 2,2,2-trichloroethylcarbonyl group.

  Specific examples of the alkoxycarbonyl group having 2 to 5 carbon atoms as the substituent of the aromatic group include a methoxycarbonyl group, an ethoxycarbonyl group, a propoxycarbonyl group, an isopropyloxycarbonyl group, a butyloxycarbonyl group, and an isobutyloxycarbonyl group. And sec-butyloxycarbonyl group or tert-butyloxycarbonyl group.

  In these alkoxycarbonyl groups, one or more alkyl groups may be substituted with halogen atoms. Specifically, 2-chloroethoxycarbonyl group, 3-chloropropyloxycarbonyl group, difluoromethoxycarbonyl group, 3 -Fluoropropyloxycarbonyl group, trifluoromethoxycarbonyl group, 2-fluoroethoxycarbonyl group, 2,2,2-trifluoroethoxycarbonyl group, 2,2,2-trichloroethoxycarbonyl group and the like can be exemplified.

  Specific examples of the alkylamino group having 1 to 4 carbon atoms as the substituent of the aromatic group include a methylamino group, an ethylamino group, a propylamino group, an isopropylamino group, a butylamino group, an isobutylamino group, sec- Examples thereof include a butylamino group and a tert-butylamino group.

  Further, one or more of these alkyl groups may be substituted with a halogen atom. Specifically, a chloromethylamino group, a 2-chloroethylamino group, a 3-chloropropylamino group, a difluoromethylamino group, 3- Examples thereof include a fluoropropylamino group, a trifluoromethylamino group, a 2-fluoroethylamino group, a 2,2,2-trifluoroethylamino group, and a 2,2,2-trichloroethylamino group.

  Specific examples of the dialkylamino group having 1 to 4 carbon atoms as the substituent for the aromatic group include dimethylamino group, diethylamino group, dipropylamino group, diisopropylamino group, dibutylamino group, diisobutylamino group Or a sec-butylamino group etc. can be illustrated.

  In addition, one or more of these alkyl groups may be substituted with a halogen atom, specifically, a di (chloromethyl) amino group, a di (2-chloroethyl) amino group, or a di (3-chloropropyl) amino group. Bis (difluoromethyl) amino group, di (3-fluoropropyl) amino group, bis (trifluoromethyl) amino group, di (2-fluoroethyl) amino group, di (2,2,2-trifluoroethyl) Examples thereof include an amino group and a di (2,2,2-trichloroethyl) amino group.

  Specific examples of the halogen atom as the substituent of the aromatic group include fluorine, chlorine, bromine and iodine.

  Examples of the palladium catalyst that can be used in the present invention include palladium metals such as palladium black and palladium sponge, and palladium / alumina, palladium / carbon, palladium / silica, palladium / Y-type zeolite, palladium / A-type zeolite. Further, supported palladium metals such as palladium / X-type zeolite, palladium / mordenite, palladium / ZSM-5 can be exemplified. Moreover, palladium chloride, palladium bromide, palladium iodide, palladium acetate, palladium trifluoroacetate, palladium nitrate, palladium oxide, palladium sulfate, palladium cyanide, sodium hexachloroparadate, potassium hexachloroparadate, sodium tetrachloroparadate, Examples of the metal salt include potassium tetrachloroparadate, potassium tetrabromoparadate, ammonium tetrachloroparadate, and ammonium hexachloroparadate.

  Furthermore, π-allyl palladium chloride dimer, palladium acetylacetonate, tetrafluoro (acetonitrile) palladium borofluoride, dichlorobis (acetonitrile) palladium, dichlorobis (benzonitrile) palladium, bis (dibenzylideneacetone) palladium, tris (dibenzylideneacetone) di Palladium, dichlorodiammine palladium, tetraammine palladium nitrate, tetraammine palladium tetrachloroparadate, dichlorodipyridine palladium, dichloro (2,2'-bipyridyl) palladium, dichloro (phenanthroline) palladium, nitrate (tetramethylphenanthroline) palladium, diphenanthroline nitrate Palladium, bis (tetramethylphenanthroline) palladium nitrate, dichlorobis (to Phenylphosphine) palladium, dichlorobis (tricyclohexylphosphine) palladium, tetrakis (triphenylphosphine) palladium, dichloro [1,2-bis (diphenylphosphino) ethane] palladium, dichloro [1,3-bis (diphenylphosphino) propane ] Complex compounds such as palladium, dichloro [1,4-bis (diphenylphosphino) butane] palladium and dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium.

  The palladium catalyst may be any of these metals, supported metals, metal salts, and complex compounds, but in terms of high yield, palladium chloride, palladium acetate, π-allyl palladium chloride dimer, bis (dibenzylideneacetone) palladium, Tris (dibenzylideneacetone) dipalladium, dichlorobis (triphenylphosphine) palladium, tetrakis (triphenylphosphine) palladium, dichloro [1,2-bis (diphenylphosphino) ethane] palladium, dichloro [1,3-bis (diphenyl) Phosphino) propane] palladium, dichloro [1,4-bis (diphenylphosphino) butane] palladium, dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium, palladium / alumina and palladium / charcoal Is desirable, tetrakis (triphenylphosphine) palladium is more preferable.

  These palladium catalysts may be used alone or in combination with a tertiary phosphine. Examples of the tertiary phosphine that can be used include triphenylphosphine, trimethylphosphine, triethylphosphine, tripropylphosphine, triisopropylphosphine, tributylphosphine, triisobutylphosphine, tri-tert-butylphosphine, trineopentylphosphine, tricyclohexyl. Phosphine, trioctylphosphine, tris (hydroxymethyl) phosphine, tris (2-hydroxyethyl) phosphine, tris (3-hydroxypropyl) phosphine, tris (2-cyanoethyl) phosphine, (+)-1,2-bis [( 2R, 5R) -2,5-diethylphosphorano] ethane, triallylphosphine, triamylphosphine, cyclohexyldiphenylphosphine, methyldiphenylphosphine Fins, ethyl diphenyl phosphine, propyl diphenylphosphine, isopropyl diphenyl phosphine, butyl diphenylphosphine, isobutyl diphenyl phosphine, tert- butyl diphenylphosphine, and the like.

  9,9-dimethyl-4,5-bis (diphenylphosphino) xanthene, 2- (diphenylphosphino) -2 ′-(N, N-dimethylamino) biphenyl, (R)-(+)-2- (Diphenylphosphino) -2′-methoxy-1,1′-binaphthyl, (−)-1,2-bis [(2R, 5R) -2,5-dimethylphosphorano] benzene, (+)-1, 2-bis [(2S, 5S) -2,5-dimethylphosphorano] benzene, (−)-1,2-bis ((2R, 5R) -2,5-diethylphosphorano) benzene, (+) − 1,2-bis [(2S, 5S) -2,5-diethylphosphorano] benzene, 1,1′-bis (diisopropylphosphino) ferrocene, (−)-1,1′-bis [(2S, 4S ) -2,4-diethylphosphorano] ferrocene, R)-(−)-1-[(S) -2- (dicyclohexylphosphino) ferrocenyl] ethyldicyclohexylphosphine, (+)-1,2-bis [(2R, 5R) -2,5-di-isopropyl Phosphorano] benzene, (−)-1,2-bis [(2S, 5S) -2,5-di-isopropylphosphorano] benzene, and the like.

  (±) -2- (di-tert-butylphosphino) -1,1′-binaphthyl, 2- (di-tert-butylphosphino) biphenyl, 2- (dicyclohexylphosphino) biphenyl, 2- ( Dicyclohexylphosphino) -2′-methylbiphenyl, bis (diphenylphosphino) methane, 1,2-bis (diphenylphosphino) ethane, 1,2-bis (dipentafluorophenylphosphino) ethane, 1,3- Bis (diphenylphosphino) propane, 1,4-bis (diphenylphosphino) butane, 1,4-bis (diphenylphosphino) pentane, 1,1′-bis (diphenylphosphino) ferrocene, (2R, 3R) -(-)-2,3-bis (diphenylphosphino) -bicyclo [2.2.1] hept-5-ene, (2S, S)-(+)-2,3-bis (diphenylphosphino) -bicyclo [2.2.1] hept-5-ene, (2S, 3S)-(−)-bis (diphenylphosphino) butane, Examples thereof include cis-1,2-bis (diphenylphosphino) ethylene and bis (2-diphenylphosphinoethyl) phenylphosphine.

  Also, (2S, 4S)-(−)-2,4-1,4-bis (diphenylphosphino) pentane, (2R, 4R)-(−)-2,4-1,4-bis (diphenylphosphine) Fino) pentane, R-(+)-1,2-bis (diphenylphosphino) propane, (2S, 3S)-(+)-1,4-bis (diphenylphosphino) -2,3-O-isopropyl Riden-2,3-butanediol, tri (2-furyl) phosphine, tri (1-naphthyl) phosphine, tris [3,5-bis (trifluoromethyl) phenyl] phosphine, tris (3-chlorophenyl) phosphine, tris (4-chlorophenyl) phosphine, tris (3,5-dimethylphenyl) phosphine, tris (3-fluorophenyl) phosphine, tris (4-fluorophenyl) phosphine , Tris (2-methoxyphenyl) phosphine, tris (3-methoxyphenyl) phosphine, tris (4-methoxyphenyl) phosphine, tris (2,4,6-trimethoxyphenyl) phosphine, tris (pentafluorophenyl) phosphine , Tris [4- (perfluorohexyl) phenyl] phosphine, and the like.

  Tris (2-thienyl) phosphine, tris (m-tolyl) phosphine, tris (o-tolyl) phosphine, tris (p-tolyl) phosphine, tris (4-trifluoromethylphenyl) phosphine, tri (2,5- Xylyl) phosphine, tri (3,5-xylyl) phosphine, 1,2-bis (diphenylphosphino) benzene, (R)-(+)-2,2′-bis (diphenylphosphino) -1,1 ′ -Binaphthyl, (S)-(-)-2,2'-bis (diphenylphosphino) -1,1'-binaphthyl, (±) -2,2'-bis (diphenylphosphino) -1,1 ' -Binaphthyl, 2,2'-bis (diphenylphosphino) -1,1'-biphenyl, (S)-(+)-4,12-bis (diphenylphosphino)-[2.2] -parasite Lophane, (R)-(−)-4,12-bis (diphenylphosphino)-[2.2] -paracyclophane, (R)-(+)-2,2′-bis (di-p- (Tolylphosphino) -1,1′-binaphthyl, (S)-(−)-2,2′-bis (di-p-tolylphosphino) -1,1′-binaphthyl, bis (2-methoxyphenyl) phenylphosphine, etc. can give.

  Also, 1,2-bis (diphenylphosphino) benzene, (1R, 2R)-(+)-N, N′-bis (2′-diphenylphosphinobenzoyl) -1,2-diaminocyclohexane, (1S, 2S)-(+)-N, N′-bis (2′-diphenylphosphinobenzoyl) -1,2-diaminocyclohexane, (±) -N, N′-bis (2′-diphenylphosphinobenzoyl)- 1,2-diaminocyclohexane, (1S, 2S)-(−)-N, N′-bis (2-diphenylphosphino-1-naphthoyl) -1,2-diaminocyclohexane, (1R, 2R)-(+ ) -N, N'-bis (2-diphenylphosphino-1-naphthoyl) -1,2-diaminocyclohexane, (±) -N, N'-bis (2-diphenylphosphino-1-naphthoyl) ) Diaminocyclohexane, tris (diethylamino) phosphine, bis (diphenylphosphino) acetylene, bis (2-diphenylphosphinophenyl) ether, (R)-(−)-1-[(S) -2- (dicyclohexylphosphino) ) Ferrocenyl] ethyldiphenylphosphine and the like.

  (R)-(−)-1-[(S) -2- (diphenylphosphino) ferrocenyl] ethyl di-tert-butylphosphine, bis (p-sulfonatophenyl) phenylphosphine dipotassium salt, 2-dicyclohexylphos Fino-2 ′-(N, N-dimethylamino) biphenyl, (S)-(−)-1- (2-diphenylphosphino-1-naphthyl) isoquinoline, tris (trimethylsilyl) phosphine, 2-di-tert- Butylphosphino-2 ′-(N, N-dimethylamino) biphenyl, 2-di-tert-butylphosphino-2′-methylbiphenyl, 2- (dicyclohexylphosphino) biphenyl, 2-dicyclohexylphosphino-2 ′ , 6'-dimethoxy-1,1'-biphenyl and 2- (dicyclohexylphosphino -2 ', 4', 6'-triisopropyl-1,1'-biphenyl and the like.

  The tertiary phosphine used may be any of the above tertiary phosphines, but in terms of good yield, triphenylphosphine, trimethylphosphine, triethylphosphine, tributylphosphine, tri (tert-butyl) phosphine, tricyclohexylphosphine, Trioctylphosphine, 9,9-dimethyl-4,5-bis (diphenylphosphino) xanthene, 2- (di-tert-butylphosphino) biphenyl, 2- (dicyclohexylphosphino) biphenyl, 1,2-bis ( Diphenylphosphino) ethane, 1,3-bis (diphenylphosphino) propane, 1,4-bis (diphenylphosphino) butane, 1,1'-bis (diphenylphosphino) ferrocene, (R)-(+) -2,2'-bis (diphenylphosphino)- , 1′-binaphthyl, (S)-(−)-2,2′-bis (diphenylphosphino) -1,1′-binaphthyl and (±) -2,2′-bis (diphenylphosphino) -1 1,1′-binaphthyl is preferred.

  Among them, triphenylphosphine, trimethylphosphine, tributylphosphine, tri (tert-butyl) phosphine, tricyclohexylphosphine, trioctylphosphine, 2- (di-tert-butylphosphino) biphenyl, 2- (dicyclohexylphosphino) biphenyl, 1,2-bis (diphenylphosphino) ethane, 1,3-bis (diphenylphosphino) propane, 1,4-bis (diphenylphosphino) butane, 1,1′-bis (diphenylphosphino) ferrocene, R)-(+)-2,2′-bis (diphenylphosphino) -1,1′-binaphthyl, (S)-(−)-2,2′-bis (diphenylphosphino) -1,1 ′ -Binaphthyl, (±) -2,2'-bis (diphenylphosphino) -1,1'-binaphth 2-di-tert-butylphosphino-2 ′-(N, N-dimethylamino) biphenyl, 2-di-tert-butylphosphino-2′-methylbiphenyl, 2- (dicyclohexylphosphino) biphenyl, 2 More preferred are -dicyclohexylphosphino-2 ', 6'-dimethoxy-1,1'-biphenyl and 2- (dicyclohexylphosphino) -2', 4 ', 6'-triisopropyl-1,1'-biphenyl.

  0.01-50 mol% is preferable with respect to aromatic amines (4), and, as for the usage-amount of a palladium catalyst, 1-20 mol% is more preferable.

  The amount of tertiary phosphine used is preferably 1 to 50000 mol%, more preferably 10 to 1000 mol%, based on the palladium compound.

  Examples of the base that can be used in this reaction include organic bases such as trimethylamine, triethylamine, diethylamine, tripropylamine, tributylamine, dibutylamine, piperidine, pyridine, lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, phosphorus Examples thereof include inorganic bases such as potassium acid, sodium-tert-butoxide, potassium-tert-butoxide, sodium hydroxide, potassium hydroxide and sodium hydride. An inorganic base is desirable in terms of a good yield, and cesium carbonate, potassium phosphate, and sodium-tert-butoxide are more desirable.

  The amount of the base used is desirably 10 to 5000 mol%, more desirably 100 to 500 mol%, based on the aromatic amines (4).

  In this reaction, 2-bromo-3,3,3-trifluoropropene itself may be used, but 1,2-dibromo-3,3,3-trifluoropropane is added to trimethylamine, triethylamine, diethylamine, tripropylamine. Alternatively, an organic base such as tributylamine, dibutylamine, piperidine or pyridine may be allowed to act to generate 2-bromo-3,3,3-trifluoropropene in the reaction system, which may be used. The amount of the organic base is preferably from 100 to 1000 mol%, more preferably from 100 to 300 mol%, based on 1,2-dibromo-3,3,3-trifluoropropane.

  The amount of 2-bromo-3,3,3-trifluoropropene or 1,2-dibromo-3,3,3-trifluoropropane used is 100 to 1000 mol% with respect to the aromatic amines (4). Is desirable, and 100 to 250 mol% is more desirable. When n is 2 in the aromatic amines (4), these amounts may be used twice.

  This reaction can be carried out in a solvent. For example, tetrahydrofuran, diethyl ether, benzene, toluene, o-xylene, m-xylene, p-xylene, dichloromethane, tetrachloroethane, acetonitrile, ethyl acetate and the like can be used. . Of these, toluene is desirable because of its good yield.

  Although there is no restriction | limiting in particular in reaction temperature, It is preferable to carry out at the temperature suitably selected from the range of -10 degreeC to solvent reflux temperature. The reaction time is 10 minutes to 48 hours depending on the reaction temperature.

  The method for isolating the target product from the solution after the reaction is not particularly limited, but may be a general method such as solvent extraction, column chromatography, preparative thin layer chromatography, preparative liquid chromatography, recrystallization or sublimation. The object can be obtained.

  The present invention only provides aromatic N- (1,1,1-trifluoro-2-propylidene) amines expected as useful intermediates for medicines, agricultural chemicals, electronic materials and the like, and an efficient production method thereof. In addition, it is also effective as an efficient method for producing other fluorine-containing aromatic imine derivatives.

  EXAMPLES Next, although an Example demonstrates this invention in detail, this invention is not limited to these.

Example 1
In a 10 mL test tube with a screw cap, 48.1 mg (0.05 mmol) of tris (dibenzylideneacetone) dipalladium, 391 mg (1.2 mmol) of cesium carbonate, (1,1′-bis (diphenylphosphino) ferrocene 83. 2 mg (0.15 mmol) was added, and the inside of the test tube was replaced with argon gas, then 2 mL of toluene was added, and the mixture was stirred at room temperature for 5 minutes, while cooling the test tube with an ice bath, 93.1 mg (1.0 mmol) of aniline. ), 250 μL (1.2 mmol) of 2-bromo-3,3,3-trifluoropropene and hexadecane as an internal standard were added and stirred for 12 hours at 110 ° C. After completion of the reaction, the solid was treated with celite. After filtration, 99% yield of N- (1,1,1-trifluoro-2-propylidene) aniline was obtained by GC analysis. The filtrate was concentrated and purified by a silica gel column (eluent hexane: ethyl acetate = 10: 1) to give the desired product as a yellow oil (92%, 172 mg). .

¹ H-NMR (CDCl ₃ , ppm): δ 2.02 (q, J _HF = 0.4 Hz, 3H), 6.79 (dt, J _HH = 8.4 Hz, J _HH = 1.1 Hz, 2H), 7.18 (tt, J _HH = 7.5 Hz, J _HH = 1.1 Hz, 1H), 7.36-7.39 (m, 2H).
¹³ C-NMR (CDCl ₃ , ppm): δ 14.4, 118.6, 119.7 (q, J _CF = 278.3 Hz), 125.2, 129.2, 147.6, 157.4 (q , J _CF = 34.0 Hz).
¹⁹ F-NMR (CDCl ₃ , ppm): −75.0 (J _FH = 0.4 Hz).
MS: M / z = 187 (molecular weight peak).

(Example 2)
In a 10 mL test tube with a screw cap, tris (dibenzylideneacetone) dipalladium 48.1 mg (0.05 mmol), cesium carbonate 391 mg (1.2 mmol), (1,1′-bis (diphenylphosphino) ferrocene 55. 5 mg (0.10 mmol) was added, the inside of the test tube was replaced with argon gas, 2 mL of toluene was added, and the mixture was stirred at room temperature for 5 minutes, while cooling the test tube with an ice bath, 93.1 mg (1.0 mmol) of aniline. ), 250 μL (1.2 mmol) of 2-bromo-3,3,3-trifluoropropene and hexadecane as an internal standard were added and stirred for 12 hours at 110 ° C. After completion of the reaction, the solid was treated with celite. After filtration, N- (1,1,1-trifluoro-2-propylidene) a was analyzed by GC analysis as in Example 1. Phosphorus was confirmed that was produced at a yield of 92%.

(Example 3)
In a 10 mL test tube with a screw cap, tris (dibenzylideneacetone) dipalladium 48.1 mg (0.05 mmol), cesium carbonate 391 mg (1.2 mmol), (1,1′-bis (diphenylphosphino) ferrocene 111 mg ( 0.20 mmol), and the inside of the test tube was replaced with argon gas, 2 mL of toluene was added, and the mixture was stirred at room temperature for 5 minutes. 250 μL (1.2 mmol) of 2-bromo-3,3,3-trifluoropropene and hexadecane as an internal standard were added, and this was heated and stirred for 12 hours at 110 ° C. After completion of the reaction, the mixture was filtered through Celite. GC analysis similar to 1 revealed that N- (1,1,1-trifluoro-2-propylidene) aniline was 8 It was confirmed that% is produced in a yield.

Example 4
In a 10 mL test tube with a screw cap, tris (dibenzylideneacetone) dipalladium 48.1 mg (0.05 mmol), cesium carbonate 391 mg (1.2 mmol), 9,9-dimethyl-4,5-bis (diphenylphosphino) ) 86.8 mg (0.15 mmol) of xanthene was added, and the inside of the test tube was replaced with argon gas. Next, 2 mL of toluene was added and stirred at room temperature for 5 minutes. While cooling the test tube in an ice bath, 93.1 mg (1.0 mmol) of aniline, 250 μL (1.2 mmol) of 2-bromo-3,3,3-trifluoropropene and hexadecane as an internal standard were added. This was heated at 110 ° C. for 12 hours and stirred. After completion of the reaction, the mixture was filtered through Celite, and it was confirmed by the same GC analysis as in Example 1 that N- (1,1,1-trifluoro-2-propylidene) aniline was produced in a yield of 83%.

(Example 5)
In a test tube with a screw cap of 10 mL, 48.1 mg (0.05 mmol) of tris (dibenzylideneacetone) dipalladium, 391 mg (1.2 mmol) of cesium carbonate, 64.0 mg (0.15 mmol) of diphenylphosphinobutane were placed. The inside of the test tube was replaced with argon gas. Next, 2 mL of toluene was added and stirred at room temperature for 5 minutes. While cooling the test tube in an ice bath, 93.1 mg (1.0 mmol) of aniline, 250 μL (1.2 mmol) of 2-bromo-3,3,3-trifluoropropene and hexadecane as an internal standard were added. This was heated at 110 ° C. for 12 hours and stirred. After completion of the reaction, the mixture was filtered through Celite, and it was confirmed by the same GC analysis as in Example 1 that N- (1,1,1-trifluoro-2-propylidene) aniline was produced in 80% yield.

(Example 6)
In a test tube with a 10 mL screw cap, 48.1 mg (0.05 mmol) of tris (dibenzylideneacetone) dipalladium, 391 mg (1.2 mmol) of cesium carbonate, (±) -2,2′-bis (diphenylphosphino) -1,1′-binaphthyl 93.4 mg (0.15 mmol) was added, and the inside of the test tube was replaced with argon gas. Next, 2 mL of toluene was added and stirred at room temperature for 5 minutes. While cooling the test tube in an ice bath, 93.1 mg (1.0 mmol) of aniline, 250 μL (1.2 mmol) of 2-bromo-3,3,3-trifluoropropene and hexadecane as an internal standard were added. This was heated at 110 ° C. for 12 hours and stirred. After completion of the reaction, the mixture was filtered through Celite, and it was confirmed by the same GC analysis as in Example 1 that N- (1,1,1-trifluoro-2-propylidene) aniline was produced in a 78% yield.

(Example 7)
In a 10 mL test tube with a screw cap, tris (dibenzylideneacetone) dipalladium 48.1 mg (0.05 mmol), sodium-tert-butoxide 115 mg (1.2 mmol), 2- (di-tert-butylphosphino) biphenyl 44.8 mg (0.15 mmol) was added, and the inside of the test tube was replaced with argon gas. Next, 2 mL of toluene was added and stirred at room temperature for 5 minutes. While cooling the test tube in an ice bath, 93.1 mg (1.0 mmol) of aniline, 250 μL (1.2 mmol) of 2-bromo-3,3,3-trifluoropropene and hexadecane as an internal standard were added. This was heated at 110 ° C. for 12 hours and stirred. After completion of the reaction, the mixture was filtered through Celite, and it was confirmed by the same GC analysis as in Example 1 that N- (1,1,1-trifluoro-2-propylidene) aniline was produced in a yield of 26%.

(Example 8)
In a 10 mL test tube with a screw cap, tris (dibenzylideneacetone) dipalladium 48.1 mg (0.05 mmol), potassium phosphate 255 mg (1.2 mmol), (1,1′-bis (diphenylphosphino) ferrocene 83 2 mg (0.15 mmol) was added, and the inside of the test tube was replaced with argon gas, then 2 mL of toluene was added, and the mixture was stirred at room temperature for 5 minutes, while cooling the test tube in an ice bath, 93.1 mg (1. 0 mmol) and 2-bromo-3,3,3-trifluoropropene (250 μL, 1.2 mmol) and hexadecane as an internal standard were added and stirred for 12 hours at 110 ° C. After completion of the reaction, the mixture was filtered through Celite. N- (1,1,1-trifluoro-2-propylidene) aniline by GC analysis as in Example 1. It was confirmed that was produced at 26% yield.

Example 9
In a 10 mL test tube with a screw cap, 48.1 mg (0.05 mmol) of tris (dibenzylideneacetone) dipalladium, 391 mg (1.2 mmol) of cesium carbonate, 83.2 mg of 1,1′-bis (diphenylphosphino) ferrocene (0.15 mmol) was added, and the inside of the test tube was replaced with argon gas. Next, 2 mL of toluene was added and stirred at room temperature for 5 minutes. While the test tube was cooled in an ice bath, 129 mg (1.0 mmol) of 2-chloroaniline and 250 μL (1.8 mmol) of 2-bromo-3,3,3-trifluoropropene were added. This was heated at 110 ° C. for 15 hours and stirred. After completion of the reaction, the solid was filtered through Celite, 2,2,2-trifluoroethanol was added as an internal standard, and 2-chloro-N- (1,1,1-trifluoro-2-propylidene was analyzed by ¹⁹ F-NMR. ) It was confirmed that aniline was produced at a production rate of 99%. The filtrate was concentrated and purified by a silica gel column (eluent hexane: chloroform = 4: 1) to obtain the desired product as a yellow oil (yield 55%, 121 mg).

¹ H-NMR (CDCl ₃ , ppm): δ 1.99 (s, 3H), 6.78 (dd, J _HH = 7.8 Hz, J _HH = 1.4 Hz, 1 H), 7.18 (ddd, J _HH = 7.8 Hz, J _HH = 7.8 Hz, J _HH = 1.4 Hz, 1 H), 7.27 (ddd, J _HH = 7.8 Hz, J _HH = 7.8 Hz, J _HH = 1.4 Hz, 1H), 7.42 (dd, J _HH = 7.8 Hz, J _HH = 1.4 Hz, 1H).
¹³ C-NMR (CDCl ₃ , ppm): δ 15.2, 119.5 (q, J _CF = 278.5 Hz), 119.6, 122.8, 126.0, 127.6, 130.2, 144 .8, 160.0 (q, J _CF = 34.4 Hz).
¹⁹ F-NMR (CDCl ₃ , ppm): −74.9.

(Example 10)
In a 10 mL test tube with a screw cap, 48.1 mg (0.05 mmol) of tris (dibenzylideneacetone) dipalladium, 391 mg (1.2 mmol) of cesium carbonate, 83.2 mg of 1,1′-bis (diphenylphosphino) ferrocene (0.15 mmol) was added, and the inside of the test tube was replaced with argon gas. Next, 2 mL of toluene was added and stirred at room temperature for 5 minutes. While the test tube was cooled in an ice bath, 127 mg (1.0 mmol) of 3-chloroaniline and 250 μL (1.8 mmol) of 2-bromo-3,3,3-trifluoropropene were added. This was heated at 110 ° C. for 15 hours and stirred. After completion of the reaction, the solid was filtered through Celite, 2,2,2-trifluoroethanol was added as an internal standard, and 3-chloro-N- (1,1,1-trifluoro-2-propylidene was analyzed by ¹⁹ F-NMR. ) It was confirmed that aniline was produced at a production rate of 95%. The filtrate was concentrated and purified by a silica gel column (eluent hexane: chloroform = 4: 1) to obtain the desired product as a yellow oil (yield 77%, 169 mg).

¹ H-NMR (CDCl ₃ , ppm): δ 2.04 (s, CH ₃ ), 6.66-6.69 (m, 1H), 6.81 (dd, J _HH = 2.0 Hz, J _HH = 2.0 Hz, 1H), 7.14-7.18 (m, 1H), 7.31 (dd, J _HH = 8.0 Hz, J _HH = 8.0 Hz, 1H).
¹³ C-NMR (CDCl ₃ , ppm): δ 14.6, 116.9, 118.8, 119.3 (q, J _CF = 276.8 Hz), 125.2, 130.4, 135.0, 148 .7, 158.5 (q, J _CF = 34.0 Hz).
¹⁹ F-NMR (CDCl ₃ , ppm): −74.9.

(Example 11)
In a 10 mL test tube with a screw cap, 48.1 mg (0.05 mmol) of tris (dibenzylideneacetone) dipalladium, 391 mg (1.2 mmol) of cesium carbonate, 83.2 mg of 1,1′-bis (diphenylphosphino) ferrocene (0.15 mmol) was added, and the inside of the test tube was replaced with argon gas. Next, 2 mL of toluene was added and stirred at room temperature for 5 minutes. While cooling the test tube in an ice bath, 175.0 mg (1.0 mmol) of 2-bromoaniline and 250 μL (1.8 mmol) of 2-bromo-3,3,3-trifluoropropene were added. This was heated at 110 ° C. for 15 hours and stirred. After completion of the reaction, the solid was filtered through Celite, 2,2,2-trifluoroethanol was added as an internal standard, and 2-bromo-N- (1,1,1-trifluoro-2-propylidene was analyzed by ¹⁹ F-NMR. ) It was confirmed that aniline was produced at a production rate of 90%.

¹ H-NMR (CDCl ₃ , ppm): δ 1.98 (s, 3H), 6.75 (dd, J _HH = 7.9 Hz, J _HH = 1.6 Hz, 1H), 7.01-7 .05 (m, 1H), 7.29-7.34 (m, 1H), 7.60 (dd, J _HH = 8.1 Hz, J _HH = 1.3 Hz, 1H).
¹³ C-NMR (CDCl ₃ , ppm): δ 15.2, 112.3, 119.3, 119.6 (q, J _CF = 278.5 Hz), 126.2, 128.3, 133.3, 146 .3, 159.8 (q, J _CF = 34.4 Hz).
¹⁹ F-NMR (CDCl ₃ , ppm): −74.9.

(Example 12)
In a 10 mL test tube with a screw cap, 48.1 mg (0.05 mmol) of tris (dibenzylideneacetone) dipalladium, 391 mg (1.2 mmol) of cesium carbonate, 83.2 mg of 1,1′-bis (diphenylphosphino) ferrocene (0.15 mmol) was added, and the inside of the test tube was replaced with argon gas. Next, 2 mL of toluene was added and stirred at room temperature for 5 minutes. While the test tube was cooled in an ice bath, 171.0 mg (1.0 mmol) of 4-bromoaniline and 250 μL (1.8 mmol) of 2-bromo-3,3,3-trifluoropropene were added. This was heated at 110 ° C. for 15 hours and stirred. After completion of the reaction, the solid was filtered through Celite, 2,2,2-trifluoroethanol was added as an internal standard, and 4-bromo-N- (1,1,1-trifluoro-2-propylidene was analyzed by ¹⁹ F-NMR. ) It was confirmed that aniline was produced at a production rate of 63%. The filtrate was concentrated and purified by a silica gel column (eluent hexane: chloroform = 4: 1) to obtain the desired product as a yellow oil (yield 52%, 138 mg).

_{^{1 H-NMR (CDCl 3,}} ppm): δ2.03 (s, 3H), 6.68 (d, J HH = 8.6Hz, 2H), 7.50 (d, J HH = 8.6 Hz, 2H).
¹³ C-NMR (CDCl ₃ , ppm): δ 14.5, 118.5, 119.6 (q, J _CF = 278.4 Hz), 120.7, 132.3, 146.5, 158.2 (q , J _CF = 34.1 Hz).
¹⁹ F-NMR (CDCl ₃ , ppm): −75.0.

(Example 13)
In a 10 mL test tube with a screw cap, 48.1 mg (0.05 mmol) of tris (dibenzylideneacetone) dipalladium, 391 mg (1.2 mmol) of cesium carbonate, 83.2 mg of 1,1′-bis (diphenylphosphino) ferrocene (0.15 mmol) was added, and the inside of the test tube was replaced with argon gas. Next, 2 mL of toluene was added and stirred at room temperature for 5 minutes. While the test tube was cooled in an ice bath, 111.0 mg (1.0 mmol) of 4-fluoroaniline and 250 μL (1.8 mmol) of 2-bromo-3,3,3-trifluoropropene were added. This was heated at 110 ° C. for 15 hours and stirred. After completion of the reaction, the solid was filtered through Celite, 2,2,2-trifluoroethanol was added as an internal standard, and 4-fluoro-N- (1,1,1-trifluoro-2-propylidene was analyzed by ¹⁹ F-NMR. ) It was confirmed that aniline was produced at a production rate of 94%. The filtrate was concentrated and purified by a silica gel column (eluent hexane: chloroform = 4: 1) to obtain the desired product as a yellow oil (yield 80%, 163 mg).

¹ H-NMR (CDCl ₃ , ppm): δ 2.04 (s, 3H), 6.75-6.80 (m, 2H), 7.08 (dd, J _HH = 8.6 Hz, J _HF = 8 .5Hz, 2H).
¹³ C-NMR (CDCl ₃ , ppm): δ 14.4, 116.1 (d, J _CF = 22.7 Hz), 119.7 (q, J _CF = 278.3 Hz), 120.6 (d, J _CF = 8.2 Hz), 143.5 (d, J _CF = 2.9 Hz), 158.0 (q, J _CF = 34.0 Hz), 160.5 (d, J _CF = 244.1 Hz).
¹⁹ F-NMR (CDCl ₃ , ppm): −75.0, −118.4 (tt, J _FH = 8.5 Hz, 4.8 Hz).

(Example 14)
In a 10 mL test tube with a screw cap, 48.1 mg (0.05 mmol) of tris (dibenzylideneacetone) dipalladium, 391 mg (1.2 mmol) of cesium carbonate, 83.2 mg of 1,1′-bis (diphenylphosphino) ferrocene (0.15 mmol) was added, and the inside of the test tube was replaced with argon gas. Next, 2 mL of toluene was added and stirred at room temperature for 5 minutes. While cooling the test tube in an ice bath, 114 mg (1.1 mmol) of 2-toluidine and 250 μL (1.8 mmol) of 2-bromo-3,3,3-trifluoropropene were added. This was heated at 110 ° C. for 15 hours and stirred. After completion of the reaction, the solid was filtered through Celite, 2,2,2-trifluoroethanol was added as an internal standard, and 2-methyl-N- (1,1,1-trifluoro-2-propylidene was analyzed by ¹⁹ F-NMR. ) It was confirmed that aniline was produced at a production rate of 99%. The filtrate was concentrated and purified by a silica gel column (eluent hexane: chloroform = 4: 1) to obtain the desired product as a yellow oil (yield 59%, 126 mg).

¹ H-NMR (CDCl 3, ppm): δ 1.96 (s, 3H), 2.08 (s, 3H), 6.60 (d, J _HH = 7.7 Hz, 1H), 7.07 (dd, _{J HH = 7.5 Hz, J HH} = 7.5Hz, 1H), 7.18 (dd, J HH = 7.7Hz, J HH = 7.5Hz, 1H), 7.22 (d, J HH = 7.5 Hz, 1 H).
¹³ C-NMR (CDCl ₃ , ppm): δ 14.5, 17.3, 117.4, 120.0 (q, J _CF = 278.4 Hz), 125.1, 126.5, 126.9, 130 .8, 146.4, 157.3 (q, J _CF = 33.8 Hz).
¹⁹ F-NMR (CDCl ₃ , ppm): −74.8.

(Example 15)
In a 10 mL test tube with a screw cap, 48.1 mg (0.05 mmol) of tris (dibenzylideneacetone) dipalladium, 391 mg (1.2 mmol) of cesium carbonate, 83.2 mg of 1,1′-bis (diphenylphosphino) ferrocene (0.15 mmol) was added, and the inside of the test tube was replaced with argon gas. Next, 2 mL of toluene was added and stirred at room temperature for 5 minutes. While cooling the test tube in an ice bath, 107 mg (1.0 mmol) of 4-toluidine and 250 μL (1.8 mmol) of 2-bromo-3,3,3-trifluoropropene were added. This was heated at 110 ° C. for 15 hours and stirred. After completion of the reaction, the solid was filtered through Celite, 2,2,2-trifluoroethanol was added as an internal standard, and 4-methyl-N- (1,1,1-trifluoro-2-propylidene was analyzed by ¹⁹ F-NMR. ) It was confirmed that aniline was produced at a production rate of 61%. The filtrate was concentrated and purified by a silica gel column (eluent hexane: chloroform = 4: 1) to obtain the desired product as a yellow oil (yield 44%, 87.5 mg).

¹ H-NMR (CDCl ₃ , ppm): δ 2.03 (s, 3H), 2.35 (s, 3H), 6.70 (d, J _HH = 8.2 Hz, 2H), 7.17 ( d, J _HH = 8.2 Hz, 2H).
¹³ C-NMR (CDCl ₃ , ppm): δ 14.3, 20.9, 119.0, 119.9 (q, J _CF = 278.2 Hz), 129.7, 134.9, 144.9, 157 .1 (q, J _CF = 33.8 Hz).
¹⁹ F-NMR (CDCl ₃ , ppm): −74.9.

(Example 16)
In a 10 mL test tube with a screw cap, 48.1 mg (0.05 mmol) of tris (dibenzylideneacetone) dipalladium, 391 mg (1.2 mmol) of cesium carbonate, 83.2 mg of 1,1′-bis (diphenylphosphino) ferrocene (0.15 mmol) was added, and the inside of the test tube was replaced with argon gas. Next, 2 mL of toluene was added and stirred at room temperature for 5 minutes. While the test tube was cooled in an ice bath, 123.5 mg (1.0 mmol) of 4-anisidine and 250 μL (1.8 mmol) of 2-bromo-3,3,3-trifluoropropene were added. This was heated at 110 ° C. for 15 hours and stirred. After completion of the reaction, the solid was filtered through Celite, 2,2,2-trifluoroethanol was added as an internal standard, and 4-methoxy-N- (1,1,1-trifluoro-2-propylidene was analyzed by ¹⁹ F-NMR. ) It was confirmed that aniline was produced at a production rate of 99%. The filtrate was concentrated and purified by a silica gel column (eluent hexane: chloroform = 4: 1) to obtain the desired product as a yellow oil (yield 59%, 128 mg).

¹ H-NMR (CDCl ₃ , ppm): δ 2.07 (s, 3H), 3.82 (s, 3H), 6.71 (d, J _HH = 9.0 Hz, 2H), 6.85 (d , J _HH = 9.0 Hz, 2H).
¹³ C-NMR (CDCl ₃ , ppm): δ 14.4, 55.5, 114.4, 120.0 (q, J _CF = 278.2 Hz), 120.9, 140.4, 156.8 (q , J _CF = 33.8 Hz), 157.4.
¹⁹ F-NMR (CDCl ₃ , ppm): −74.8.

(Example 17)
In a 10 mL test tube with a screw cap, 48.1 mg (0.05 mmol) of tris (dibenzylideneacetone) dipalladium, 391 mg (1.2 mmol) of cesium carbonate, 83.2 mg of 1,1′-bis (diphenylphosphino) ferrocene (0.15 mmol) was added, and the inside of the test tube was replaced with argon gas. Next, 2 mL of toluene was added and stirred at room temperature for 5 minutes. While the test tube was cooled in an ice bath, 159 mg (1.0 mmol) of 2-trifluoromethylaniline and 250 μL (1.8 mmol) of 2-bromo-3,3,3-trifluoropropene were added. This was heated at 110 ° C. for 15 hours and stirred. After completion of the reaction, the solid was filtered through Celite, 2,2,2-trifluoroethanol was added as an internal standard, and 2-trifluoromethyl-N- (1,1,1-trifluoro-2) was determined by ¹⁹ F-NMR. -Propyridene) aniline was confirmed to be produced at a production rate of 38%. The filtrate was concentrated and purified by a silica gel column (eluent hexane: chloroform = 4: 1) to obtain the desired product as a yellow oil (yield 40%, 99.9 mg).

¹ H-NMR (CDCl ₃ , ppm): δ 1.97 (s, 3H), 6.73 (d, J _HH = 7.8 Hz, 1 H), 7.26 (dd, J _HH = 7.8 Hz, J _{HH = 7.7Hz, 1H), 7.54} (dd, J HH = 7.8Hz, J HH = 7.7Hz, 1H), 7.68 (d, J HH = 7.8Hz, 1H).
¹³ C-NMR (CDCl ₃ , ppm): δ 15.1, 118.6, 119.2 (q, J _CF = 278.4 Hz), 119.3 (q, J _CF = 31.2 Hz), 123.5 (Q, J _CF = 272.9 Hz), 124.9, 126.8 (q, J _CF = 5.1 Hz), 132.9, 146.1, 159.7 (J _CF = 34.8 Hz).
¹⁹ F-NMR (CDCl ₃ , ppm): −75.4, −62.2.

(Example 18)
In a 10 mL test tube with a screw cap, 48.1 mg (0.05 mmol) of tris (dibenzylideneacetone) dipalladium, 391 mg (1.2 mmol) of cesium carbonate, 83.2 mg of 1,1′-bis (diphenylphosphino) ferrocene (0.15 mmol) was added, and the inside of the test tube was replaced with argon gas. Next, 2 mL of toluene was added and stirred at room temperature for 5 minutes. While the test tube was cooled in an ice bath, 161 mg (1.0 mmol) of 3-trifluoromethylaniline and 250 μL (1.8 mmol) of 2-bromo-3,3,3-trifluoropropene were added. This was heated at 110 ° C. for 15 hours and stirred. After completion of the reaction, the solid was filtered through Celite, 2,2,2-trifluoroethanol was added as an internal standard, and 3-trifluoromethyl-N- (1,1,1-trifluoro-2) was determined by ¹⁹ F-NMR. -Propyridene) aniline was confirmed to be produced at a production rate of 99%.

¹ H-NMR (CDCl ₃ , ppm): δ 2.04 (s, 3H), 6.97 (d, J _HH = 7.9 Hz, 1H), 7.06 (s, 1H), 7.45 (d , J _HH = 7.8 Hz, 1 H), 7.50 (dd, J _HH = 7.9 Hz, J _HH = 7.8 Hz, 1 H).
¹³ C-NMR (CDCl ₃ , ppm): δ 14.6, 115.7 (q, J _CF = 3.8 Hz), 119.5 (q, J _CF = 278.4 Hz), 122.0 (q, J _CF = 3.8 Hz), 122.1, 123.8 (q, J _CF = 272.4 Hz), 130.0, 131.9 (q, J _CF = 32.7 Hz), 148.1, 158.9 (Q, J _CF = 34.5 Hz).
¹⁹ F-NMR (CDCl ₃ , ppm): −75.1, −63.2.

(Example 19)
In a 10 mL test tube with a screw cap, 48.1 mg (0.05 mmol) of tris (dibenzylideneacetone) dipalladium, 391 mg (1.2 mmol) of cesium carbonate, 83.2 mg of 1,1′-bis (diphenylphosphino) ferrocene (0.15 mmol) was added, and the inside of the test tube was replaced with argon gas. Next, 2 mL of toluene was added and stirred at room temperature for 5 minutes. While the test tube was cooled in an ice bath, 150.2 mg (1.0 mmol) of 4-tert-butylaniline and 250 μL (1.8 mmol) of 2-bromo-3,3,3-trifluoropropene were added. This was heated at 110 ° C. for 15 hours and stirred. After completion of the reaction, the solid was filtered through Celite, 2,2,2-trifluoroethanol was added as an internal standard, and 4-tert-butyl-N- (1,1,1-trifluoro-2) was detected by ¹⁹ F-NMR. -Propyridene) aniline was confirmed to be produced at a production rate of 99%. The filtrate was concentrated and purified by a silica gel column (eluent hexane: chloroform = 4: 1) to obtain the desired product as a yellow oil (yield 57%, 138.5 mg).

¹ H-NMR (CDCl ₃ , ppm): δ 1.33 (s, 9H), 2.04 (s, 3H), 6.73 (d, J _HH = 6.8 Hz, 2H), 7.38 (d , J _HH = 6.8 Hz, 2H).
¹³ C-NMR (CDCl ₃ , ppm): δ 14.4, 31.3, 34.4, 118.7, 120.0 (q, J _CF = 278.2 Hz), 125.9, 144.8, 148 .2,156.9 (q, J _CF = 33.8 Hz).
¹⁹ F-NMR (CDCl ₃ , ppm): −74.9.

(Example 20)
In a 10 mL test tube with a screw cap, 48.1 mg (0.05 mmol) of tris (dibenzylideneacetone) dipalladium, 391 mg (1.2 mmol) of cesium carbonate, 83.2 mg of 1,1′-bis (diphenylphosphino) ferrocene (0.15 mmol) was added, and the inside of the test tube was replaced with argon gas. Next, 2 mL of toluene was added and stirred at room temperature for 5 minutes. While the test tube was cooled in an ice bath, 176 mg (1.0 mmol) of 2-trifluoromethoxyaniline and 250 μL (1.8 mmol) of 2-bromo-3,3,3-trifluoropropene were added. This was heated at 110 ° C. for 15 hours and stirred. After completion of the reaction, the solid was filtered through Celite, 2,2,2-trifluoroethanol was added as an internal standard, and 2-trifluoromethoxy-N- (1,1,1-trifluoro-2) was determined by ¹⁹ F-NMR. -Propyridene) aniline was confirmed to be produced at a production rate of 99%. The filtrate was concentrated and purified by a silica gel column (eluent hexane: chloroform = 4: 1) to obtain the desired product as a yellow oil (yield 63%, 169.2 mg).

¹ H-NMR (CDCl ₃ , ppm): δ2.00 (s, 3H), 6.85-6.87 (m, 1H), 7.19-7.23 (m, 1H), 7.30- 7.33 (m, 2H).
¹³ C-NMR (CDCl ₃ , ppm): δ 15.2, 119.0 (q, J _CF = 278.4 Hz), 121.0 (q, J _CF = 258.3 Hz), 120.7, 122.5 , 126.2, 127.7, 137.7, 140.4, 160.3 (q, J _CF = 34.5 Hz).
¹⁹ F-NMR (CDCl ₃ , ppm): −58.4, −75.1.

(Example 21)
In a 10 mL test tube with a screw cap, 48.1 mg (0.05 mmol) of tris (dibenzylideneacetone) dipalladium, 391 mg (1.2 mmol) of cesium carbonate, 83.2 mg of 1,1′-bis (diphenylphosphino) ferrocene (0.15 mmol) was added, and the inside of the test tube was replaced with argon gas. Next, 2 mL of toluene was added and stirred at room temperature for 5 minutes. While the test tube was cooled in an ice bath, 165.8 mg (1.0 mmol) of ethyl 2-aminobenzoate and 250 μL (1.8 mmol) of 2-bromo-3,3,3-trifluoropropene were added. This was heated at 110 ° C. for 15 hours and stirred. After completion of the reaction, the solid was filtered through Celite, 2,2,2-trifluoroethanol was added as an internal standard, and 2- [N- (1,1,1-trifluoro-2-propylidene) was analyzed by ¹⁹ F-NMR. It was confirmed that ethyl amino] benzoate was produced at a production rate of 32%.

¹ H-NMR (CDCl ₃ , ppm): δ 1.34 (t, J _HH = 7.2 Hz, 3H), 1.96 (s, 3H), 4.30 (q, J _HH = 7.2 Hz, 2H) ), 6.67-6.69 (m, 1H), 7.19-7.23 (m, 1H), 7.49-7.53 (m, 1H), 8.03 (dd, J _HH = 7.9 Hz, J _HH = 1.3 Hz, 1H).
¹³ C-NMR (CDCl ₃ , ppm): δ 14.1, 15.1, 61.2, 118.8, 119.5, 120.0 (q, J _CF = 278.2 Hz), 124.5, 131 .6, 133.3, 148.5, 157.4 (q, J _CF = 34.4 Hz), 165.7.
¹⁹ F-NMR (CDCl ₃ , ppm): −75.1.

(Example 22)
In a 10 mL test tube with a screw cap, 48.1 mg (0.05 mmol) of tris (dibenzylideneacetone) dipalladium, 391 mg (1.2 mmol) of cesium carbonate, 83.2 mg of 1,1′-bis (diphenylphosphino) ferrocene (0.15 mmol) was added, and the inside of the test tube was replaced with argon gas. Next, 2 mL of toluene was added and stirred at room temperature for 5 minutes. While cooling the test tube with an ice bath, 115.7 mg (1.0 mmol) of 3-ethynylaniline and 250 μL (1.8 mmol) of 2-bromo-3,3,3-trifluoropropene were added. This was heated at 110 ° C. for 15 hours and stirred. After completion of the reaction, the solid was filtered through Celite, 2,2,2-trifluoroethanol was added as an internal standard, and 3-ethynyl-N- (1,1,1-trifluoro-2-propylidene was analyzed by ¹⁹ F-NMR. ) It was confirmed that aniline was produced at a production rate of 63%.

¹⁹ F-NMR (CDCl ₃ , ppm): −75.0.

(Example 23)
In a 10 mL test tube with a screw cap, 48.1 mg (0.05 mmol) of tris (dibenzylideneacetone) dipalladium, 391 mg (1.2 mmol) of cesium carbonate, 83.2 mg of 1,1′-bis (diphenylphosphino) ferrocene (0.15 mmol) was added, and the inside of the test tube was replaced with argon gas. Next, 2 mL of toluene was added and stirred at room temperature for 5 minutes. While the test tube was cooled in an ice bath, 136 mg (1.0 mmol) of 4-aminoacetophenone and 250 μL (1.8 mmol) of 2-bromo-3,3,3-trifluoropropene were added. This was heated at 110 ° C. for 15 hours and stirred. After completion of the reaction, the solid was filtered through Celite, 2,2,2-trifluoroethanol was added as an internal standard, and 4- [N- (1,1,1-trifluoro-2-propylidene) was analyzed by ¹⁹ F-NMR. It was confirmed that amino] acetophenone was produced at a production rate of 23%.

¹⁹ F-NMR (CDCl ₃ , ppm): −75.1.

(Example 24)
In a 10 mL test tube with a screw cap, 48.1 mg (0.05 mmol) of tris (dibenzylideneacetone) dipalladium, 391 mg (1.2 mmol) of cesium carbonate, 83.2 mg of 1,1′-bis (diphenylphosphino) ferrocene (0.15 mmol) was added, and the inside of the test tube was replaced with argon gas. Next, 2 mL of toluene was added and stirred at room temperature for 5 minutes. While cooling the test tube with an ice bath, 120.3 mg (1.0 mmol) of 3-aminobenzonitrile and 250 μL (1.8 mmol) of 2-bromo-3,3,3-trifluoropropene were added. This was heated at 110 ° C. for 15 hours and stirred. After completion of the reaction, the solid was filtered through Celite, 2,2,2-trifluoroethanol was added as an internal standard, and 3-cyano-N- (1,1,1-trifluoro-2-propylidene was analyzed by ¹⁹ F-NMR. ) It was confirmed that aniline was produced at a production rate of 84%.

¹⁹ F-NMR (CDCl ₃ , ppm): −75.1.

(Example 25)
In a 10 mL test tube with a screw cap, 48.1 mg (0.05 mmol) of tris (dibenzylideneacetone) dipalladium, 391 mg (1.2 mmol) of cesium carbonate, 83.2 mg of 1,1′-bis (diphenylphosphino) ferrocene (0.15 mmol) was added, and the inside of the test tube was replaced with argon gas. Next, 2 mL of toluene was added and stirred at room temperature for 5 minutes. While the test tube was cooled in an ice bath, 125.5 mg (1.0 mmol) of 3,5-dimethylaniline and 250 μL (1.8 mmol) of 2-bromo-3,3,3-trifluoropropene were added. This was heated at 110 ° C. for 15 hours and stirred. After completion of the reaction, the solid was filtered through Celite, 2,2,2-trifluoroethanol was added as an internal standard, and 3,5-dimethyl-N- (1,1,1-trifluoro-2) was measured by ¹⁹ F-NMR. -Propyridene) aniline was confirmed to be produced at a production rate of 99%. The filtrate was concentrated and purified by a silica gel column (eluent hexane: chloroform = 4: 1) to obtain the desired product as a yellow oil (yield 89%, 198 mg).

¹ H-NMR (CDCl ₃ , ppm): δ 2.02 (s, 3H), 2.31 (s, 6H), 6.40 (s, 2H), 6.80 (s, 1H).
¹³ C-NMR (CDCl ₃ , ppm): δ 14.3, 21.2, 116.2, 120 (q, J _CF = 278.3 Hz), 126.6, 138.9, 147.6, 155.4 (Q, J _CF = 33.8 Hz).
¹⁹ F-NMR (CDCl ₃ , ppm): −75.0.

(Example 26)
In a 10 mL test tube with a screw cap, 48.1 mg (0.05 mmol) of tris (dibenzylideneacetone) dipalladium, 391 mg (1.2 mmol) of cesium carbonate, 83.2 mg of 1,1′-bis (diphenylphosphino) ferrocene (0.15 mmol) was added, and the inside of the test tube was replaced with argon gas. Next, 2 mL of toluene was added and stirred at room temperature for 5 minutes. While the test tube was cooled in an ice bath, 127.8 mg (1.0 mmol) of 2-fluoro-5-methylaniline and 250 μL (1.8 mmol) of 2-bromo-3,3,3-trifluoropropene were added. This was heated at 110 ° C. for 15 hours and stirred. After completion of the reaction, the solid was filtered through Celite, 2,2,2-trifluoroethanol was added as an internal standard, and 2-fluoro-5-methyl-N- (1,1,1-trifluoro) was analyzed by ¹⁹ F-NMR. -2-propylidene) aniline was confirmed to be produced at a production rate of 83%. The filtrate was concentrated and purified by a silica gel column (eluent hexane: chloroform = 4: 1) to obtain the desired product as a yellow oil (yield 59%, 132.5 mg).

¹ H-NMR (CDCl ₃ , ppm): δ 2.02 (d, J _HF = 1.7 Hz, 3H), 2.32 (s, 3H), 6.70-6.72 (m, 1H), 6 .91-6.94 (m, 1H), 7.01-7.02 (m, 1H).
¹³ C-NMR (CDCl ₃ , ppm): δ 15.1 (d, J _CF = 3.1 Hz), 20.6, 115.8 (d, J _CF = 19.7 Hz), 119.0 (q, J _CF = 278.3 Hz), 122.1 (d, J _CF = 1.1 Hz), 126.9 (d, J _CF = 4.5 Hz), 134.4 (d, J _CF = 2.1 Hz), 134 .44 (d, J _CF = 19.1 Hz), 149.1 (d, J _CF = 243.8 Hz), 159.9 (q, J _CF = 34.2 Hz).
¹⁹ F-NMR (CDCl ₃ , ppm): −74.8, −131.6 (brs).

(Example 27)
In a 10 mL test tube with a screw cap, 48.1 mg (0.05 mmol) of tris (dibenzylideneacetone) dipalladium, 391 mg (1.2 mmol) of cesium carbonate, 83.2 mg of 1,1′-bis (diphenylphosphino) ferrocene (0.15 mmol) was added, and the inside of the test tube was replaced with argon gas. Next, 2 mL of toluene was added and stirred at room temperature for 5 minutes. While cooling the test tube in an ice bath, 117.4 mg (1.0 mmol) of 4-vinylaniline and 250 μL (1.8 mmol) of 2-bromo-3,3,3-trifluoropropene were added. This was heated at 110 ° C. for 15 hours and stirred. After completion of the reaction, the solid was filtered through Celite, 2,2,2-trifluoroethanol was added as an internal standard, and 4-vinyl-N- (1,1,1-trifluoro-2-propylidene was analyzed by ¹⁹ F-NMR. ) It was confirmed that aniline was produced at a production rate of 77%. The filtrate was concentrated and purified by a silica gel column (eluent hexane: chloroform = 4: 1) to obtain the desired product as a yellow oil (yield 42%, 89.3 mg).

¹ H-NMR (CDCl ₃ , ppm): δ 2.04 (s, 3H), 5.24 (d, J _HH = 10.9 Hz, 1 H), 5.73 (d, J _HH = 17.6 Hz, 1 H ), 6.70 (dd, J _HH = 10.9 Hz, J _HH = 17.6 Hz, 1 H), 6.77 (d, J _HH = 8.4 Hz, 2 H), 7.42 (d, J _HH = 8.4 Hz, 2H).
¹³ C-NMR (CDCl ₃ , ppm): δ 14.5, 113.6, 119.2, 119.7 (q, J _CF = 278.3 Hz), 127.0, 134.8, 136.0, 147 0.0, 157.4 (q, J _CF = 33.9 Hz).
¹⁹ F-NMR (CDCl ₃ , ppm): −74.9.

(Example 28)
In a 10 mL test tube with a screw cap, 48.1 mg (0.05 mmol) of tris (dibenzylideneacetone) dipalladium, 391 mg (1.2 mmol) of cesium carbonate, 83.2 mg of 1,1′-bis (diphenylphosphino) ferrocene (0.15 mmol) was added, and the inside of the test tube was replaced with argon gas. Next, 2 mL of toluene was added and stirred at room temperature for 5 minutes. While the test tube was cooled in an ice bath, 130 mg (1.0 mmol) of 3,4-difluoroaniline and 250 μL (1.8 mmol) of 2-bromo-3,3,3-trifluoropropene were added. This was heated at 110 ° C. for 15 hours and stirred. After completion of the reaction, the solid was filtered through Celite, 2,2,2-trifluoroethanol was added as an internal standard, and 3,4-difluoro-N- (1,1,1-trifluoro-2) was measured by ¹⁹ F-NMR. It was confirmed that -propylidene) aniline was produced at a production rate of 58%. The filtrate was concentrated and purified by a silica gel column (eluent hexane: chloroform = 4: 1) to obtain the desired product as a yellow oil (yield 43%, 95 mg).

¹ H-NMR (CDCl ₃ , ppm): δ 2.05 (s, 3H), 6.52 (dddd, J _HH = 8.7 Hz, J _HF = 3.8 Hz, J _HH = 2.5 Hz, J _HF = 1.8 Hz, 1 H), 6.67 (ddd, J _HF = 10.7 Hz, J _HF = 6.9 Hz, J _HH = 2.5 Hz, 1 H), 7.18 (ddd, J _HF = 10.1 Hz, _{J HH = 8.7Hz, J HF =} 8.5Hz, 1H).
¹³ C-NMR (CDCl ₃ , ppm): δ 14.5, 108.7 (d, J _CF = 19.5 Hz), 114.8 (dd, J _CF = 6.1 Hz, J _CF = 3.7 Hz), _{117.9 (dd, J CF = 18.3Hz} , J CF = 1.3Hz), 119.4 (q, J CF = 278.4Hz), 144 (dd, J CF = 6.8Hz, J CF = 3 .3 Hz), 148.0 (dd, J _CF = 246.4 Hz, J _CF = 12.6 Hz), 150.6 (dd, J _CF = 250.1 Hz, J _CF = 13.6 Hz), 159.0 ( dq, J _CF = 34.4 Hz, J _CF = 1.3 Hz).
_{^{19 F-NMR (CDCl 3,}} ppm): - 75.0, -135.9 (dddd, J FF = 21.4Hz, J FH = 10.7Hz, J FH = 8.5Hz, J FH = 1.8Hz _{), - 142.5 (dddd, J} FF = 21.4Hz, J FH = 10.1Hz, J FH = 6.9Hz, J FH = 3.8Hz).

(Example 29)
In a 10 mL test tube with a screw cap, 48.1 mg (0.05 mmol) of tris (dibenzylideneacetone) dipalladium, 391 mg (1.2 mmol) of cesium carbonate, 83.2 mg of 1,1′-bis (diphenylphosphino) ferrocene (0.15 mmol) was added, and the inside of the test tube was replaced with argon gas. Next, 2 mL of toluene was added and stirred at room temperature for 5 minutes. While cooling the test tube in an ice bath, 161 mg (1.0 mmol) of 4-difluoromethoxyaniline and 250 μL (1.8 mmol) of 2-bromo-3,3,3-trifluoropropene were added. This was heated at 110 ° C. for 15 hours and stirred. After completion of the reaction, the solid substance was filtered through Celite, 2,2,2-trifluoroethanol was added as an internal standard, and 4-difluoromethoxy-N- (1,1,1-trifluoro-2-butyl ether was analyzed by ¹⁹ F-NMR. It was confirmed that propylidene) aniline was produced at a production rate of 99%. The filtrate was concentrated and purified by a silica gel column (eluent hexane: chloroform = 4: 1) to obtain the desired product as a yellow oil (yield 69%, 177 mg).

¹ H-NMR (CDCl ₃ , ppm): δ 2.03 (s, 3H), 6.50 (t, J _HF = 73.8 Hz, 1H), 6.80 (d, J _HH = 8.8 Hz, 2H) ), 7.15 (d, J _HH = 8.8 Hz, 2H).
¹³ C-NMR (CDCl ₃ , ppm): δ 14.5, 116.0 (t, J _CF = 260.0 Hz), 119.7 (q, J _CF = 278.3 Hz), 120.7, 120.8 , 144.9, 148.5 (t, J _CF = 2.9 Hz), 158.2 (q, J _CF = 34.1 Hz).
¹⁹ F-NMR (CDCl ₃ , ppm): −75.0, −81.2 (d, J _FH = 73.8 Hz).

(Example 30)
In a 10 mL test tube with a screw cap, palladium acetate 22.4 mg (0.10 mmol), cesium carbonate 391 mg (1.2 mmol), 1,1′-bis (diphenylphosphino) ferrocene 83.2 mg (0.15 mmol). The test tube was replaced with argon gas. Next, 2 mL of toluene was added and stirred at room temperature for 5 minutes. While cooling the test tube in an ice bath, 94.1 mg (1.0 mmol) of 3-aminopyridine and 250 μL (1.8 mmol) of 2-bromo-3,3,3-trifluoropropene were added. This was heated at 110 ° C. for 15 hours and stirred. After completion of the reaction, the solid was filtered through Celite, 2,2,2-trifluoroethanol was added as an internal standard, and 3- [N- (1,1,1-trifluoro-2-propylidene) was analyzed by ¹⁹ F-NMR. It was confirmed that amino] pyridine was produced at a production rate of 58%. The filtrate was concentrated and purified by a silica gel column (eluent hexane: chloroform = 4: 1) to obtain the desired product as a yellow oil (yield 39%, 73.4 mg).

^{_{1 H-NMR (CDCl 3,}} ppm): 2.06 (s, 3H), 7.16 (ddd, J HH = 8.0Hz, J HH = 2.4Hz, J HH = 1.5Hz, 1H), 7.33 (dd, J _HH = 8.0 Hz, J _HH = 4.8 Hz, 1 H), 8.13 (d, J _HH = 2.4 Hz, 1 H), 8.44 (dd, J _HH = 4. 8 Hz, J _HH = 1.5 Hz, 1 H).
¹³ C-NMR (CDCl ₃ , ppm): 14.6, 119.4 (J _CF = 278.3 Hz), 123.7, 126.5, 140.0, 143.4, 146.8, 159.2 (J _CF = 34.5 Hz).
¹⁹ F-NMR (CDCl ₃ , ppm): −75.0.

(Example 31)
In a 10 mL test tube with a screw cap, 57.5 mg (0.10 mmol) of bis (dibenzylideneacetone) palladium, 391 mg (1.2 mmol) of cesium carbonate, 83.2 mg of 1,1′-bis (diphenylphosphino) ferrocene ( 0.15 mmol) was added, and the inside of the test tube was replaced with argon gas. Next, 2 mL of toluene was added and stirred at room temperature for 5 minutes. While cooling the test tube in an ice bath, 157.2 mg (1.0 mmol) of 2-amino-3-methoxycarbonylthiophene and 250 μL (1.8 mmol) of 2-bromo-3,3,3-trifluoropropene were added. . This was heated at 110 ° C. for 15 hours and stirred. After completion of the reaction, the solid was filtered through Celite, 2,2,2-trifluoroethanol was added as an internal standard, and 2- [N- (1,1,1-trifluoro-2-propylidene) was analyzed by ¹⁹ F-NMR. It was confirmed that methyl amino] thiophene-3-carboxylate was produced at a production rate of 15%. The filtrate was concentrated and purified by a silica gel column (eluent hexane: chloroform = 4: 1) to obtain the desired product as a yellow oil (yield 4%, 10.0 mg).

¹ H-NMR (CDCl ₃ , ppm): 2.13 (s, 3H), 3.80 (s, 3H), 7.00 (d, J _HH = 5.6 Hz, 1H), 7.33 (d , J _HH = 5.6 Hz, 1 H).
¹³ C-NMR (CDCl ₃ , ppm): 15.7, 51.7, 117.6, 119.0, 119.2 (q, J _CF = 278.3 Hz), 128.2, 155.3, 162 .2 (q, J _CF = 34.7 Hz), 162.7.
¹⁹ F-NMR (CDCl ₃ , ppm): −74.9.
It was also confirmed by ¹⁹ F-NMR that methyl 2- [N- (1-trifluoromethylvinyl) amino] thiophene-3-carboxylate was produced in the reaction solution at a yield of 14%. . The filtrate was concentrated and purified by a silica gel column (eluent hexane: chloroform = 4: 1) to obtain the desired product as a yellow oil (yield 6%, 14.8 mg).

¹ H-NMR (CDCl ₃ , ppm): 3.87 (s, 3H), 5.23 (d, J _HH = 3.7 Hz, 1H), 5.27 (m, 1H), 6.54 (d , J _HH = 5.7 Hz, 1H), 7.19 (d, J _HH = 5.7 Hz, 1H), 9.89 (1H).
¹³ C-NMR (CDCl ₃ , ppm): 51.6, 94.5 (q, J _CF = 3.9 Hz), 110.0, 110.2, 121.1 (q, J _CF = 274.5 Hz) , 125.4, 134.3 (q, J _CF = 33.0 Hz), 155.3, 166.1.
¹⁹ F-NMR (CDCl ₃ , ppm): −71.1 (brs).

(Example 32)
In a 10 mL test tube with a screw cap, tris (dibenzylideneacetone) dipalladium 91.8 mg (0.10 mmol), cesium carbonate 782 mg (2.4 mmol), 1,1′-bis (diphenylphosphino) ferrocene 166.3 mg (0.30 mmol) was added, and the inside of the test tube was replaced with argon gas. Next, 4 mL of toluene was added and stirred at room temperature for 5 minutes. While cooling the test tube in an ice bath, 108.1 mg (1.0 mmol) of o-phenylenediamine and 450 μL (4.3 mmol) of 2-bromo-3,3,3-trifluoropropene were added. This was heated at 110 ° C. for 15 hours and stirred. After completion of the reaction, the solid was filtered through Celite, and the filtrate was concentrated and purified by a silica gel column (eluent hexane: ethyl acetate = 12: 1) to give N- (1,1,1-trimethyl) as a yellow oil. Fluoro-2-propylidene) -N ′-(1-trifluoromethylvinyl) -o-phenylenediamine was obtained (34% yield, 101.3 mg).

¹ H-NMR (CDCl ₃ , ppm): 1.57 (s, 3H), 2.63 (d, J _HH = 14.2 Hz, 1 H), 2.81 (d, J _HH = 14.2 Hz, 1 H ), 3.71 (s, 1H), 6.88 (dd, J _HH = 7.7 Hz, J _HH = 1.5 Hz, 1 H), 7.12 (ddd, J _HH = 7.7 Hz, J _HH = 7.7 Hz, J _HH = 1.5 Hz, 1 H), 7.17 (ddd, J _HH = 7.7 Hz, J _HH = 7.7 Hz, J _HH = 1.5 Hz, 1 H), 7.32 (dd, _{J HH = 7.7Hz, J HH =} 1.5Hz, 1H).
¹³ C-NMR (CDCl ₃ , ppm): 23.1, 31.9, 72.9 (q, J _CF = 25.7 Hz), 119.9 (q, J _CF = 276.7 Hz), 122.2 , 123.2, 126.1 (q, J _CF = 288.3 Hz), 129.5, 129.6, 136.9, 154.9 (q, J _CF = 35.1 Hz).
¹⁹ F-NMR (CDCl ₃ , ppm): −72.3, −81.5.

(Example 33)
In a 10 mL test tube with a screw cap, 57.5 mg (0.10 mmol) of bis (dibenzylideneacetone) palladium, 391 mg (1.2 mmol) of cesium carbonate, 83.2 mg of 1,1′-bis (diphenylphosphino) ferrocene ( 0.15 mmol) was added, and the inside of the test tube was replaced with argon gas. Next, 2 mL of toluene was added and stirred at room temperature for 5 minutes. While the test tube was cooled in an ice bath, 143.9 mg (1.0 mmol) of 1-aminonaphthalene and 250 μL (1.8 mmol) of 2-bromo-3,3,3-trifluoropropene were added. This was heated at 110 ° C. for 15 hours and stirred. After completion of the reaction, the solid was filtered through Celite, 2,2,2-trifluoroethanol was added as an internal standard, and 1- [N- (1,1,1-trifluoro-2-propylidene) was detected by ¹⁹ F-NMR. It was confirmed that amino] naphthalene was produced at a production rate of 98%. The filtrate was concentrated and purified by a silica gel column (eluent hexane: ethyl acetate = 8: 1) to obtain the desired product as a yellow oil (yield 92%, 217.7 mg).

¹ H-NMR (CDCl ₃ , ppm): 2.00 (s, 3H), 6.75 (dd, J _HH = 7.3 Hz, J _HH = 0.8 Hz, 1H), 7.44 (dd, J _{HH = 8.2Hz, J HH = 7.3Hz} , 1H), 7.47 (ddd, J HH = 8.2Hz, J HH = 6.9Hz, J HH = 1.4Hz, 1H), 7.51 ( ddd, J _HH = 8.2 Hz, J _HH = 6.9 Hz, J _HH = 1.3 Hz, 1H), 7.67 (d, J _HH = 8.2 Hz, 2H), 7.85 (dd, J _HH = 8.2 Hz, J _HH = 1.3 Hz, 1H).
¹³ C-NMR (CDCl ₃ , ppm): 14.7, 112.9, 119.7 (q, J _CF = 278.6 Hz), 122.7, 125.1, 125.3, 125.4, 126 .2,126.6,128.1,134.0,143.8,158.6 (q, J _CF = 34.0 Hz).
¹⁹ F-NMR (CDCl ₃ , ppm): −74.5.

(Example 34)
In a 10 mL test tube with a screw cap, 57.5 mg (0.10 mmol) of bis (dibenzylideneacetone) palladium, 391 mg (1.2 mmol) of cesium carbonate, 83.2 mg of 1,1′-bis (diphenylphosphino) ferrocene ( 0.15 mmol) was added, and the inside of the test tube was replaced with argon gas. Next, 2 mL of toluene was added and stirred at room temperature for 5 minutes. While the test tube was cooled in an ice bath, 144.6 mg (1.0 mmol) of 5-amino-2-methylindole and 250 μL (1.8 mmol) of 2-bromo-3,3,3-trifluoropropene were added. This was heated at 110 ° C. for 15 hours and stirred. After completion of the reaction, the solid was filtered through Celite, 2,2,2-trifluoroethanol was added as an internal standard, and 2-methyl-5- [N- (1,1,1-trifluoro-) was analyzed by ¹⁹ F-NMR. It was confirmed that 2-propylidene) amino] indole was produced at a production rate of 42%. The filtrate was concentrated and purified by a silica gel column (eluent hexane: ethyl acetate = 8: 1) to obtain the desired product as a yellow oil (yield 30%, 72.2 mg).

¹ H-NMR (CDCl ₃ , ppm): 2.08 (s, 3H), 2.45 (d, J _HH = 0.8 Hz, 3H), 6.20 (q, J _HH = 0.8 Hz, 1H) ), 6.63 (dd, J _HH = 8.3 Hz, J _HH = 1.9 Hz, 1 H), 6.93 (d, J _HH = 1.9 Hz, 1 H), 7.27 (d, J _HH = 8.3 Hz, 1H), 7.89 (brs, 1H).
¹³ C-NMR (CDCl ₃ , ppm): 13.7, 14.4, 100.7, 109.7, 110.5, 114.0, 120.1 (q, J _CF = 278.3 Hz), 129 3, 134.0, 136.4, 140.3, 156.1 (q, J _CF = 33.2 Hz).
¹⁹ F-NMR (CDCl ₃ , ppm): −74.7.

(Example 35)
In a 10 mL test tube with a screw cap, 57.5 mg (0.10 mmol) of bis (dibenzylideneacetone) palladium, 391 mg (1.2 mmol) of cesium carbonate, 83.2 mg of 1,1′-bis (diphenylphosphino) ferrocene ( 0.15 mmol) was added, and the inside of the test tube was replaced with argon gas. Next, 2 mL of toluene was added and stirred at room temperature for 5 minutes. While the test tube was cooled in an ice bath, 150.0 mg (1.0 mmol) of 6-aminobenzothiazole and 250 μL (1.8 mmol) of 2-bromo-3,3,3-trifluoropropene were added. This was heated at 110 ° C. for 15 hours and stirred. After completion of the reaction, the solid was filtered through Celite, 2,2,2-trifluoroethanol was added as an internal standard, and 6- [N- (1,1,1-trifluoro-2-propylidene) was analyzed by ¹⁹ F-NMR. It was confirmed that amino] benzothiazole was produced at a production rate of 21%. The filtrate was concentrated and purified by a silica gel column (eluent hexane: ethyl acetate = 8: 1) to obtain the desired product as a yellow oil (yield 19%, 46.7 mg).

¹ H-NMR (CDCl ₃ , ppm): 2.07 (s, 3H), 6.98 (dd, J _HH = 8.6 Hz, J _HH = 2.0 Hz, 1 H), 7.37 (d, J _HH = 2.0 Hz, 1H), 8.13 (d, J _HH = 8.6 Hz, 1H), 8.95 (s, 1H).
¹³ C-NMR (CDCl ₃ , ppm): 14.7, 111.2, 118.4, 119.6 (q, J _CF = 278.5 Hz), 124.2, 134.8, 145.3, 151 0.0, 153.4, 158.4 (q, J _CF = 34.2 Hz).
¹⁹ F-NMR (CDCl ₃ , ppm): −74.9.

(Example 36)
In a 10 mL test tube with a screw cap, 57.5 mg (0.10 mmol) of bis (dibenzylideneacetone) palladium, 391 mg (1.2 mmol) of cesium carbonate, 83.2 mg of 1,1′-bis (diphenylphosphino) ferrocene ( 0.15 mmol) was added, and the inside of the test tube was replaced with argon gas. Next, 2 mL of toluene was added and stirred at room temperature for 5 minutes. While the test tube was cooled in an ice bath, 192.0 mg (1.0 mmol) of 2-aminoanthracene and 250 μL (1.8 mmol) of 2-bromo-3,3,3-trifluoropropene were added. This was heated at 110 ° C. for 15 hours and stirred. After completion of the reaction, the solid was filtered through Celite, 2,2,2-trifluoroethanol was added as an internal standard, and 2- [N- (1,1,1-trifluoro-2-propylidene) was analyzed by ¹⁹ F-NMR. It was confirmed that amino] anthracene was produced at a production rate of 59%. The filtrate was concentrated and purified by a silica gel column (eluent hexane: chloroform = 8: 1) to obtain the desired product as a yellow powder (yield 27%, 77.2 mg).

¹ H-NMR (CDCl ₃ , ppm): 2.13 (s, 3H), 7.03 (dd, J _HH = 8.9 Hz, J _HH = 1.5 Hz, 1 H), 7.30 (d, J _{HH = 1.5Hz, 1H), 7.46} (ddd, J HH = 8.3Hz, J HH = 6.0Hz, J HH = 2.2Hz, 1H), 7.48 (ddd, J HH = 8. _{3Hz, J HH = 6.0Hz, J} HH = 2.2Hz, 1H), 7.98 (dd, J HH = 8.3Hz, J HH = 2.2Hz, 1H), 8.00 (dd, J HH = 8.3 Hz, J _HH = 2.2 Hz, 1 H), 8.04 (d, J _HH = 8.9 Hz, 1 H), 8.36 (s, 1 H), 8.43 (s, 1 H).
¹³ C-NMR (CDCl ₃ , ppm): 14.7, 118.7, 119.8 (q, J _CF = 278.3 Hz), 120.1, 125.4, 125.8, 125.9, 126 5, 127.9, 128.3, 129.6, 129.8, 131.4, 131.5, 132.3, 144.5, 157.7 (q, J _CF = 33.9 Hz).
¹⁹ F-NMR (CDCl ₃ , ppm): −74.8.

(Comparative Example 1)
According to the method of Non-Patent Document 1, 100 mg (1.1 mmol) of aniline and 105 μL (1.2 mmol) of 1,1,1-trifluoroacetone were stirred in 0.3 mL of benzene at room temperature for 2 days. After completion of the reaction, the filtrate was concentrated and purified by a silica gel column (eluent hexane: chloroform = 8: 1) to obtain the desired product as a yellow oil (yield 22%, 44 mg).

(Comparative Example 2)
According to the method of Non-Patent Document 1, 133 mg (1.1 mmol) of 3,5-dimethylaniline and 105 μL (1.2 mmol) of 1,1,1-trifluoroacetone were stirred in 0.3 mL of benzene at room temperature for 2 days. did. After completion of the reaction, 2,2,2-trifluoroethanol was added to the reaction solution as an internal standard, and 3,5-dimethyl-N- (1,1,1-trifluoro-2-propylidene) aniline was analyzed by ¹⁹ F-NMR. Was confirmed to be produced at a production rate of 40%. The filtrate was concentrated and purified by a silica gel column (eluent hexane: chloroform = 8: 1) to obtain the desired product as a yellow oil (yield 28%, 60 mg).

(Comparative Example 3)
According to the method of Non-Patent Document 1, 142 mg (1.1 mmol) of 3,4-difluoroaniline and 105 μL (1.2 mmol) of 1,1,1-trifluoroacetone were stirred in 0.3 mL of benzene at room temperature for 2 days. did. After completion of the reaction, 2,2,2-trifluoroethanol was added to the reaction solution as an internal standard, and 3,4-difluoro-N- (1,1,1-trifluoro-2-propylidene) aniline was analyzed by ¹⁹ F-NMR. Was confirmed to be produced at a production rate of 5%.

(Comparative Example 4)
According to the method of Non-Patent Document 1, 140 mg (1.1 mmol) of 2-chloroaniline and 105 μL (1.2 mmol) of 1,1,1-trifluoroacetone were stirred in 0.3 mL of benzene at room temperature for 2 days. After completion of the reaction, 2,2,2-trifluoroethanol was added to the reaction solution as an internal standard, and 2-chloro-N- (1,1,1-trifluoro-2-propylidene) aniline was produced by ¹⁹ F-NMR. It was confirmed that the product was produced at a rate of 3%.

(Comparative Example 5)
According to the method of Non-Patent Document 1, 178 mg (1.1 mmol) of 2-trifluoromethylaniline and 105 μL (1.2 mmol) of 1,1,1-trifluoroacetone were stirred in 0.3 mL of benzene at room temperature for 2 days. did. After completion of the reaction, 2,2,2-trifluoroethanol as an internal standard was added to the reaction solution, and 2-trifluoromethyl-N- (1,1,1-trifluoro-2-propylidene) aniline was analyzed by ¹⁹ F-NMR. Was confirmed to be produced at a production rate of 2%.

(Reference Example 1)
In the autoclave, 2.0 g (10.7 mmol) of N- (1,1,1-trifluoro-2-propylidene) aniline obtained in Examples 1 to 8, 10 mL of toluene, and 50 mg of palladium / carbon supported on 10 wt% were added. Hydrogen at 5 atm was introduced at room temperature. The autoclave was heated to 100 ° C. and stirred for 12 hours. After cooling, the solid was filtered. The filtrate was concentrated and purified by a silica gel column (eluent hexane: ethyl acetate = 3: 1) to obtain pale yellow oily N- (1,1,1-trifluoro-2-propyl) aniline. (Yield 49%, 999 mg).

¹ H-NMR (CDCl ₃ , ppm): 1.40 (d, J _HH = 7.0 Hz, 3H), 3.55 (brs, 1H), 3.93-4.20 (m, 1H), 6 .60-6.70 (m, 2H), 6.72-6.83 (m, 1H), 7.11-7.28 (m, 2H).

Claims (5)

General formula (1)

[In the formula, Ar represents an optionally substituted aromatic group. n represents 1 or 2. X is the formula (2)

A (1,1,1-trifluoro-2-propylidene) amino group represented by the formula (3), which is a tautomer of the formula (2)

(1-trifluoromethylvinyl) amino group represented by the formula: However, when n is 2, X may be the same or different. An aromatic amine represented by the formula: [excluding N- (1,1,1-trifluoro-2-propylidene) aniline].   The aromatic amine according to claim 1, wherein the aromatic group is an optionally substituted phenyl group, naphthyl group, anthryl group, pyridyl group, thienyl group, indolyl group or benzothiazolyl group. Except for N- (1,1,1-trifluoro-2-propylidene) aniline]. General formula (4)

[Wherein, Ar and n have the same meaning as described above. Wherein the aromatic amine compound and 2-bromo-3,3,3-trifluoropropene are reacted in the presence of a palladium catalyst and a base.

[Wherein, Ar, X and n have the same meaning as described above. ] The manufacturing method of aromatic amines represented by this.   The aromatic amine according to claim 3, wherein the aromatic group is an optionally substituted phenyl group, naphthyl group, anthryl group, pyridyl group, thienyl group, indolyl group or benzothiazolyl group. Production method. The production method according to claim 3 or 4, wherein the palladium catalyst is a catalyst system comprising a palladium compound and a tertiary phosphine.