Trifluoromethylation of aniline

Kinetic studies of the trifluoromethylation of aniline with 5-salt 17, dinitro 5-salt 39, and nonheterocyclic 5-salt 29 were carried out and the activation parameters determined (Table I). 

Kinetic Parameters for the Trifluoromethylation of Aniline with 5-(Trifluoromethyl)dibenzothiophenium Triflate (17), S-(Trifluoromethyl)diphenylsulfonium Triflate (29), AND 5-(Trifluoromethyl)-3,7-DINITRODIBENZOTHIOPHENIUM TrIFLATE (39) IN DMF-d7 AT 25°C... 

The product is free from secondary aniline product on the basis of infrared and n.m.r. proton analysis. If equimolar amounts of aniline and phosphate are employed, the product is obtained in a higher yield (12.3 g., 65%), but it contains a trace of w-trifluoromethyl-N-methylaniline as detected by infrared analysis. This secondary aniline is readily removed by heating the product to reflux with 1 ml. of acetic anhydride followed by... 

The described method of dialkylation of anilines is essentially that of Billman and co-workers. It has not previously been applied to m-trifiuoromethylaniline. m-Trifluoromethyl-N,N-dimethylaniline has been prepared in 29% yield by alkylating m-trifluoromethylaniline with methyl iodide. ... 

The reactivity of aromatic molecules in fluorination reactions with trifluoromethyl hypofluorite has been studied in detail, and in the case of aniline derivatives the effect of the substituent on nitrogen on the relative reactivity and ortho/para ratio in various aprotic nonpolar, aprotic polar and protic solvents has been determined.5... 

Jouannetaud and co-workers229 have explored electrophilic trifluoromethylation under superacidic conditions of aniline derivatives229 and /V-heterocycles. Methyl-substituted anilines and substituted acetanilides [Eq. (5.85)] react with the CC13+ cation generated from CC14 in HF-SbF5 followed by fluorination to yield the corresponding trifluoromethyl derivatives. Under similar conditions, indolines are transformed to the 6-triluoromethyl derivatives, whereas substituted indoles yield 5-triluoromethyl derivatives.230... 

Aromatic primary amines are not only binucleophiles at the amino group, but they also exhibit the properties of C,N-binucleophiles. Their reactions with internal perfluoroolefins lead to quinoline derivatives (98JFC(88)169, 94JCS(CC)134, 98T4949). Thus the reaction of aniline with 2//-heptafluorobut-2-ene yields phenyl(2-trifluoromethylquinolin-4-yl) amine (00ZOR109) when the reaction is carried out with the tetrafluoro-ethylene trimer, it leads to 2-trifluoromethyl-3-(l-N-phenylimino-2,2,2-trifluoroethyl)-4-(N-phenylamino)quinoline (98JFC(88)169). 

The synthesis of aniline derivatives can also be realized by direct addition of the NH2 unit, if the arene ring is made more electrophilic through activation by a trifluoromethyl group. For example, in the case of p-trifluoromethykhlorobenzenetricarbonylchromium complex 47, the aniline derivative 48 can be obtained in 32 % yield using NaNH2/NH3 in HMPT (Scheme 22) [11]. 

A high-yield preparation of 2- and 4-trifluoromethyl-2-quinolinones was sought. Depending on reaction conditions, the condensation of anilines with ethyl 4,4,4-trifluoroacetoacetate <03S2005> led to two different quinolinones as shown. 

Similar trifluoromethylation reactions of anilines, phenols or pyrroles were performed in the presence of sodium dithionite (ref. 27). 

The Ir complexes are capable of affording trifluoromethylation of the different anilines 96 with Togni s reagent 97 as a sonrce of the CF radical to afford 98 (Eq. 9.19) [71]. When the para position has no snbstitnent, a mixtnre of prodncts is obtained ... 

Xie J, Yuan X, Abdukader A, Zhu C, Ma J (2014) Visible-light-promoted radical C-H trifluoromethylation of free anilines. Org Lett 16 1768-1771. doi 10.1021/ol500469a... 

The section highlights synthesis of compounds demonstrated physiological activities using fluoro- or trifluoromethyl-substituted furans as starting compounds. Acylation of aniline 287 with 5-fluorofuran-2-carbonyl chloride gave amide 288 which inhibited c-jun A-terminal kinase at submicromolar level [162],... 

Umemoto [23] reported the preparation of 0-(trifluoromethyl)-dibenzofuranium salts and their use as CFj-transfer agents based on studies of L. Yagupol skii [24]. The direct 0- and iV-trifluoromethylation of alcohols, phenols, amines, anilines and pyridines under mild conditions was described. 

Reaction of aniline (304) and ethyl trifluoroacetoacetate (305) resulted in formation of 4-trifluoromethylquinolin-2-one (306) from which 2-brom-4-trifluoromethyl-quinoline (307) was synthesized further. Reaction of compound 307 with pyridines 308 at the presence of a palladium complex as the catalyst resulted in quinoline ligands 309 [185] (Scheme 88). 

The acid-catalyzed condensation of anilines with ethyl 4,4,4-trifluoro acetoace-tate affords l,4-dihydro-2-trifluoromethyl-4H-4-quinolinones, which can easily be converted into 4-bromo-2-(trifluoromethyl)quinolines (Scheme 34) [55],... 

Cyclizations of alkynyl derivatives proved to be a synthetically convenient way to 2-(trifluoromethyl)quinolines. Indeed, the intramolecular cyclization of N-(a-trifluoromethyl)propargyl anilines 89 takes place with the gold(I) catalyst under extremely mild conditions to afford 2-trifluoromethylquinolines 90 (Scheme 36). The reaction mechanism has been suggested to involve cyclization and oxidation steps [57],... 

Condensation of anilines with ethyl 4,4,4-trifluoroacetoacetate have been established to give the corresponding 4,4,4-tiifluoro-3-oxobutane substituted anilides, precursors in the synthesis of 4-(trifluoro-methyl)-2-quinolinones 111 [84], Heating of these compounds with phosphoryl tribromide affords 2-bromo-4-(trifluoro-methyOquinolines which can be converted into 4-(trifluoromethyl) quinolines 110 by reductive debromination (Scheme 55) [85]. 

Besides cyclizations of hetaryl acetonitriles, the reactions of isocyanate 845 with anilines were studied. In presence of base the reaction leads to N-aUcylidene-N-arylureas 879. The compounds 879 bearing the C=N bond activated by trifluoromethyl group undergo thermal intramolecular cyclization to give 4-trifluoromethyl-l,2,3,4-tetrahydroquinazolin-2-ones 880 in good yields. A wide range of anilines... 

The dipole moments of aniline,/-(trifluoromethyl)anihne, and (trifluoromethyl)benzene are 1.3, 4.3, and 2.9 D, respectively. Explain how these data are used to deduce the direction of the dipole moment of anihne. 

Bromo-Ar,Ar-dimethyl-3-(trifluoromethyl)aniline has been prepared by the methylation of 4-bromo-3-(trifhioromethvl)aniline with trimethyl phosphate in 70-80% yield.3 The present method, which effectively uses 3-(trifluoroinethyl)aniline as starting material, offers advantages in cost, yield, and ease of purification. 

Aniline, 2-chloro- [Benzenamine 2-chloro-], p-bromination of, 55, 23 Aniline, 3 chloro- [Benzenamine, 3-chloro-], p bjomination of, 55, 23 Aniline, //.A -diethyl- [Benzenamine, N,N-diethyl-], p-bromination of, 55, 23 Aniline,TV,//-dimethyl- [Benzenamine, N,N-dimethyl-], p-brommation of, 55, 23 Aniline, 2,3-dimethyl- [Benzenamine, 2,3-dimethyl-], p-bromination of, 55, 23 Aniline, 2,5-dimethyl- [Benzenamine, 2,5-dimethyl-], p-biomination of, 55,23 Aniline, 3,5-dimethyl [Benzenamine, 3,5-dimethyl ], p bromination of, 55,23 Aniline, Ar,iV-dimethyl-3-(trifluoromethyl) [Benzenamine, At,Ar-dimethyl-3-tn-fluoromethyl-], 55,21 Aniline, 3-methoxy- [Benzenamine, 3-methoxy-], p-bromination of, 55, 23 Aniline, TV-methyl- [Benzenamine, //-methyl-], p-biomination of, 55, 23 Aniline, 2-methyl-//,JV-dimethyl- [Benzen-amme, 2/V,/V-tnmethyl-], p-bromina-tion of, 55, 23... 

However, when an electron-withdrawing group, e.g., a trifluoromethyl group, is attached to the anilines this procedure is not applicable. A way to circumvent this problem was enlightened by Glasnov et al. [53] who treated the malondianilide 14 with Eaton s reagent, a 7.7% solution of phosphorus pen-toxide in methanesulfonic acid (a. Scheme 6) [54]. This reaction is, however, sensitive to time, temperature, and concentration. More reactive malondian-... 

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