One-Pot Tandem Access to Phenothiazine Derivatives from Acetanilide and 2-Bromothiophenol via Rhodium-Catalyzed C–H Thiolation and Copper-Catalyzed C–N Amination

Abstract

A one-pot and step economic reaction involving Rh­(III)-catalyzed C–H thiolation and relay Cu­(II)-catalyzed C–N amination of acetanilide and 2-bromothiophenol is reported here, with several valuable phenothiazine products obtained. This synthesis protocol proceeds from easily starting materials, demonstrating high atom economy, broad substrate scope, and good yield. Furthermore, the directing group can be easily eliminated, and chlorpromazine is provided in a large scale; thus this synthesis protocol could be utilized to construct phenothiazine scaffolds.

Transition metal catalysed direct sulfanylation of unreactive C–H bonds: an overview of the last two decades

“…Also in 2021, the same group reported the one-pot synthesis of phenothiazines (135) using acetanilides (133) and 2-bromothiophenol derivatives (26) as the synthetic precursors (Scheme 101). 71 It is important to mention the generality of the synthetic procedure, where high atom economy and a large substrate scope is a great advantage for the synthesis of interesting and valuable products. The best reaction conditions required a Rh(III) source and AgOAc/Cu(OTf ) 2 for catalyst activation.…”

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

“…18 A one-pot, rhodium( iii )-catalysed C–H thioarylation reaction and copper-catalysed C–N amination of acetanilides and 2-bromobenzenethiols has also been reported (Scheme 1c). 19 In addition to transition metal-catalysed approaches, various base-, enzyme- and iodine-mediated couplings have also recently been described for phenothiazine synthesis. 20…”

Reduction system “vitamin C/glycerol” promoted copper(II)‐catalyzed N‐arylation

“…Copper-catalyzed Ullmann-type reaction is the classical method for the construction of the C-N bond. [1,2] In general, (I) and (II) valence coppers were commonly utilized in numerous reactions. [3] These univalent salts, such as CuI, CuBr, CuCl, Cu 2 O, Cu 2 SO 4 and CuNO 3 , are well known, and bivalent salts usually involve CuO, CuSO 4 , CuCl 2 , CuBr 2 , Cu(OAc) 2 and Cu(OTf) 2 .…”