Metal‐Free Direct C–H Thiolation and Thiocyanation of Pyrazolones

Abstract

Metal‐free approach for direct C–H thiolation and thiocyanation of N‐substituted pyrazolones with disulfides and thiocyanate salts, respectively, are developed. These reactions allow the C–S bond coupling to proceed effectively under mild conditions, providing useful and convenient methods for preparation of a series of 4‐thio‐substituted pyrazolone analogues, which have potential applications in organic, medicinal and material chemistry. Preliminary mechanistic investigation suggested that radical processes are likely to involve in these transformations.

Transition Metal‐Free Sulfenylation of C−H Bonds for C−S Bond Formation in Recent Years: Mechanistic Approach and Promising Future

“…Removal of proton from the cationic intermediate 117 B resulted into desired sulfenylated pyrazolones ( 117 ) (Scheme 38). [137] …”

“…Eventually, it was proposed that NH 4 SCN reacts with K proton from intermediate 115 B to afford the desired 4thiocyanated 5-hydroxypyrazoles (115) (Scheme 37). [136] Recently, Kittikool and co-workers [137] have developed a transition metal-free, K 2 S 2 O 8 mediated sulfenylation of pyrazolones (116) using dialkyl disulfide (2) and ammonium thiocyanate (114) as sulfenylating reagents. The thiocyanation of pyrazolones (118) was carried out with ammonium thiocyanate in presence of K 2 S 2 O 8 at room temperature whereas, thioalkylation (117) requires KI as promoter at 60 °C.…”

“…[155] In 2019, Teng and co-workers [156] have reported visible light mediated CDC methodology for CÀ S bond formation. Rose Bengal has been used in a blue light induced methodology for sulfenylation of quinoxalin-2(1H)-ones (137) with thiols ( 9) as sulfenylating reagent. The optimized reaction condition established after initial screening with different solvents, photocatalysts and light sources was successfully applied for the synthesis of 3-sulfenyl quinoxalin-2(1H)-ones (138) using a variety of aliphatic, aromatic and heteroaryl thiols.…”

PhICl2/NH4SCN‐Mediated Oxidative Regioselective Thiocyanation of Pyridin‐2(1H)‐ones

“…The majority of the reported methods describing electrophilic thiocyanation [ 14g,15 ] of aromatic or heteroaromatic compounds such as electron‐rich phenyl rings, indoles, quinolones, and so on, involve the formation of a SCN radical from the reaction of a thiocyanate salt with an appropriate oxidant (Scheme 1a). For example, in 2019, Zhu and co‐wokers [ 14b ] reported the formation of thiocyanated pyrazoline derivatives via the Cu(II)‐catalyzed domino cyclization/thiocyantion of alkenes using K 2 S 2 O 8 as an oxidant and NH 4 SCN as thiocyanate source.…”

I2‐Promoted Direct C−H Sulfenylation of Isoquinolin‐1(2H)‐ones with Sulfonyl Chlorides

“…Significant progress has been made in the formation of C−S bonds through the direct functionalization of C−H under different conditions [12] . In this transformation, various sulfenylating or thiolating reagents have been used, such as thiols, [13] disulfides, [12c,14] sodium sulfinates, [15] sulfonyl hydrazides, [16] and sulfonyl chlorides [17] . Among them, sulfonyl chloride is easily available and inexpensive, does not have the unpleasant odor of thiols or disulfides, and usually used as a sulfonylation reagent to build C−S bonds.…”