Thioarylation of anilines using dual catalysis: two-step synthesis of phenothiazines

Abstract

A two-step synthesis of phenothiazines has been developed using a dual-catalytic ortho-thioarylation reaction of anilines as the key step. Activation of N-(2-bromophenylthio)succinimide was achieved using the super Lewis acid, iron(III)...

Regioselective Functionalization of Arenes Using Iron Triflimide Catalysis

“…The development of this process was investigated using benzoyl-protected p -toluidine (Scheme 22 ). 48 Attempted thioarylation using iron(III) triflimide at 10 mol% loading and a 90 °C reaction temperature showed no reaction after 48 h. Based on our previous study, several Lewis bases were screened to promote and accelerate the transformation. Bis(4-methoxyphenyl)sulfane was again shown to be effective, generating the product in 88% yield.…”

“…Using the diphenyl selenide accelerated thioarylation reaction, a two-pot process was developed for the synthesis of phenothiazines (Scheme 23 ). 48 For electron-rich anilines, N -protection was necessary to avoid competing N -thioarylation. Under the optimized conditions, clean and high-yielding thioarylation reactions were observed.…”

“…An application of the two-step approach for the preparation of phenothiazines was demonstrated with a short synthesis of the neuroleptic agent methopromazine. 48 50 Thioarylation of N -benzoyl-protected 3-methoxyaniline using the dual Lewis acid and Lewis base procedure gave the ortho -substituted product in 64% yield. Using a slightly lower reaction temperature (75 °C) than the standard conditions of 90 °C allowed controlled monothioarylation at the para position to the methoxy group.…”

Regioselective C–H Thiocyanation of Arenes by Iron(III) Chloride Catalysis

“…We have shown that iron(III) salts can act as Lewis acids for the activation of N -halosuccinimides and the subsequent regioselective halogenation of arenes . More recently, we have shown that iron(III) triflimide can activate N -thioaryl succinimides for the preparation of unsymmetrical biaryl sulfides . Based on this previous work, we proposed that an iron(III) salt may function as an activator of an N -thiocyanating reagent, allowing efficient thiocyanation of a wide range of arenes, without the requirement of acidic conditions or long reaction times.…”

Synthesis of Thiazoloindole α-Amino Acids: Chromophores Amenable to One- and Two-Photon Induced Fluorescence

“…Recently, reported methods for the syntheses of [3,2- a ]­thiazoloindoles have typically involved the preparation of N- or C2-alkynyl-substituted indoles, followed by base-mediated cyclization . Instead, we proposed an alternative two-step approach, utilizing a regioselective C2-thioarylation of the tryptophan indole ring via iron­(III) and diphenyl selenide dual-catalyzed activation of N -thiosuccinimide 7 , − followed by a copper-mediated N-arylation reaction between the ortho -bromide substituent and the adjacent indole amine (Scheme ). It was then proposed that the [3,2- a ]­thiazoloindole ring system could be extended, allowing substituent-based tuning of the photophysical properties, by regioselective bromination, followed by a Suzuki–Miyaura cross-coupling reaction.…”