Diaryl and Heteroaryl Sulfides: Synthesis via Sulfenyl Chlorides and Evaluation as Selective Anti-Breast-Cancer Agents

Abstract

A mild protocol for the synthesis of diaryl and heteroaryl sulfides is described. In a one-pot procedure, thiols are converted to sulfenyl chlorides and reacted with arylzinc reagents. This method tolerates functional groups including aryl fluorides and chlorides, ketones, as well as N-heterocycles including pyrimidines, imidazoles, tetrazoles, and oxadiazoles. Two compounds synthesized by this method exhibited selective activity against the MCF-7 breast cancer cell line in the micromolar range.

Metal-Free Iodine-Catalyzed Direct Arylthiation of Substituted Anilines with Thiols

“…We have compared different oxidants (compare entries 1, 5 and 6), and DTBP was superior to the other oxidants (entry 1). In addition, Various temperatures were investigated (entries [7][8][9], and 120 o C was discovered to be more suitable for this transformation (entry 9). Elevated the reaction temperature did not enahance the yield (entry 12, Table 1).…”

“…Elevated the reaction temperature did not enahance the yield (entry 12, Table 1). Besides that, different amounts of DTBP were used in the reactions (entries [9][10][11], and the 5 equiv. of DTBP provided the highest yield (entry 9).…”

Synthesis of aryl sulfides via radical–radical cross coupling of electron-rich arenes using visible light photoredox catalysis

“…Typical metals used are palladium [ 10 – 13 ], copper [ 14 – 21 ], nickel [ 22 – 24 ], iron [ 25 – 29 ], cobalt [ 30 – 32 ], and rhodium [ 33 – 34 ]. Aryl sulfides are also synthesized by cross coupling of thiols and aryl Grignard/arylzinc reagents [ 35 – 36 ]. However, most of these methods require harsh reaction conditions, external additives and high temperatures.…”

Novel conformationally constrained pyrazole derivatives as potential anti-cancer agents

“…Indicatively, carbazoles possessing a unique tricyclic ring system have been permitted for the treatment of cancer [5], while phenazines [6] and several piperazines [7] have been found to display IC 50 values in the nanomolar range against quinone reductase inhibitors. Recently, azoaryl sulfides were proved as selective antibreast cancer agents with IC 50 values in the low micromolar range [8,9]. In this respect, pyrazoles that constitute a prominent family among azaheterocycles comprise a class of molecules with a prominent position in the anticancer portfolio as having been evidenced in numerous publications [10].…”