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

Abstract

Main observation and conclusion The reaction of pyridin‐2(1H)‐ones with PhICl2 and NH4SCN enables an efficient regioselective thiocyanation, leading to the synthesis of the biologically interesting C5 thiocyanated 2‐pyridones in good to high yields. The mechanistic pathway of this metal‐free approach is postulated to involve the formation of the reactive thiocyanogen chloride from the reaction of PhICl2 and NH4SCN followed with the regioselective electrophilic thiocyanation of the pyridin‐2(1H)‐one ring.

Electrophilic Oxythio/selenocyanation of o‐Alkenyl Benzoic Acids: Divergent Synthesis of Thio/selenocyanated Isobenzofuranones and Isocoumarins

“…Based on the control experiments and previous literature reports, [11,13–14,20] a plausible mechanistic pathway for the selective oxythio/selenocyanation processes were proposed (Scheme 4), taking the reaction of NH 4 SCN as an example. Initially, the reaction of PhICl 2 with NH 4 SCN in DCM generated the reactive electrophilic species Cl−SCN in situ [16a,b] . Then, the reaction of surplus thiocyanate salt with Cl−SCN delivered (SCN) 2 , which reacted further with the other molecule of PhICl 2 to give Cl−SCN species.…”

Recent progress of direct thiocyanation reactions

“…In 2021, an efficient regioselective sp 2 C–H thiocyanation of pyridin-2(1 H )-ones 59 with NH 4 SCN in the presence of the oxidant PhICl 2 was reported by Du's group. A wide array of thiocyanato 2-pyridones 60 were obtained in good to high yields, 28 as shown in Scheme 20. The mechanistic pathway involved the formation of the reactive thiocyanogen chloride from the reaction of PhICl 2 and NH 4 SCN followed by the regioselective electrophilic thiocyanation of the pyridin-2(1 H )-one ring.…”

“…The product SCN-containing 2-thiazoline could further react with sulfuric acid, sodium azide, diphenyl phosphoric acid, (trifluoromethyl) trifluorosilane and DDQ, providing the corresponding products in up to 92% yield.In 2021, an efficient regioselective sp 2 C-H thiocyanation of pyridin-2(1H)-ones 59 with NH 4 SCN in the presence of the oxidant PhICl 2 was reported by Du's group. A wide array of thiocyanato 2-pyridones 60 were obtained in good to high yields,28 Scheme 17 Synthesis of vinyl thiocyanate derivatives.Scheme 18 Thiocyanation of disulfur-substituted alkenes.…”

Self‐ or Acridinium‐Catalyzed Electrophotosynthesis of Thiocyanato Heterocycles from Activated Alkenes

“…They are also versatile synthons which could be converted with ease to other sulfur-containing molecules such as thiols, thioethers, carbamothioates, thiotetrazole, perfluoromethylsulfanes and phosphinothioates. [23] Over the past decades, a wide range of methodologies have been developed to construct organic thiocyanates using an N-SCN agent, [24] TMSSCN [25] or KSCN, [26][27][28][29][30][31][32][33][34] or through sulfur cyanation. [35] The inexpensive and benchtop-stable KSCN is a particularly versatile thiocyanating agent, which might undergo a nucleophilic, [26][27][28][29] electrophilic [30,31] or radical coupling [32][33][34] under the conditions of an oxidant, [26,30,32] visible-light irradiation [27,33] or electrolysis.…”