Experimental and computational studies of trifluoromethylation of aromatic amines by the system trifluoroiodomethane‐zinc‐sulfur dioxide

Abstract

Several trifluoromethyl‐substituted aromatic and heteroaromatic amines have been obtained by the reactions of the corresponding amines with the title reagent system. Computational results provide rationalization for the observed regioselectivities and support a mechanism in which the electrophilic trifluoromethyl radicals interact with the aromatic ring at the sites with the greatest electron density of the HOMO orbitals, and then the resultant adducts are oxidized to cations. The products obtained are potential building blocks for a number of heterocyclic systems.

Trifluoromethylation of various aromatic compounds by CF3I in the presence of Fe(II) compound, H2O2 and dimethylsulfoxide

“…The protonation possibly occurred both at N atom in the ring and at the amino group. 8-Aminoquinoline exhibited much higher reactivity than quinoline and all the trifluoromethylated positions of the products were ortho-and para-positions of the amino group on benzene ring [13]. Therefore, the protonation possibly occurred at the nitrogen atom in the ring; this protonation should little affect the reactivity of the benzene ring.…”

“…Indeed, the reaction using pyridine afforded a trace amount of certain trifluoromethylated products [18]. In contrast, 3-aminopyridine (entry 1) gave a moderate yield of ortho-oriented 3-amino-2-trifluoromethylpyridine (9a) in the absence of H 2 SO 4 (method D) [13], suggesting that the amino group works effectively as an electron-donating group. Remarkably high total yield of ortho-and para-oriented trifluoromethylated products were obtained from 2,6-diaminopyridine even in the presence of H 2 SO 4 (entry 2).…”

“…However, these methods seem practically unsuitable because of the reagents and/or apparatus required. CF 3 I, which is one of the available radical sources of a trifluoromethyl radical [11], was also utilized for radical trifluoromethylation under photoirradiation [12] or in the presence of Zn/ SO 2 [13]; trifluoromethylation by a trifluoromethyl radical formed from CF 3 I thermally is also known despite the low yield [14]. Recently, we found that trifluoromethyl radicals can be generated from CF 3 I with a reagent composed of FeSO 4 , H 2 O 2 and dimethylsulfoxide (DMSO), which is the alkylation reagent of aromatic and hetero-aromatic compounds with alkyl and perfluoroalkyl iodides [15], and that various nucleobases were able to be trifluoromethylated by CF 3 I and this reagent [16].…”

Synthesis of quinolines and acridines by the reaction of 2-(perfluoroalkyl)anilines with lithium and Grignard reagents

“…Interestingly, the trifluoromethylation of 3 is ortho-regioselective [21]. Common substituents R 1 are well tolerated in the preparation of 2.…”

“…These starting materials 2 (Scheme 1) are inexpensive commercial products or can easily be prepared by perfluoroalkylation of 2-haloanilines 1 or anilines 3 [18][19][20][21]. Interestingly, the trifluoromethylation of 3 is ortho-regioselective [21].…”