Highly Efficient and Practical Thiocyanation of Imidazopyridines Using an N‐Chlorosuccinimide/NaSCN Combination

Abstract

A direct C–H thiocyanation of imidazo[1,2‐a]pyridines, and a practical sequential one‐pot condensation/C–H thiocyanation process, using a combination of N‐chlorosuccinimide/NaSCN for the synthesis of 3‐thiocyanatoimidazo[1,2‐a]pyridines have been developed. The reactions are environmentally friendly, and easy to carry out. They use readily available starting materials and mild reaction conditions, show a wide functional group tolerance, and give good to excellent yields.

Catalytic Thiourea Promoted Electrophilic Thiocyanation of Indoles and Aromatic Amines with NCS/NH4SCN

“…Conventionally, these procedures involved the use of rather unstable (SCN) 2 or XSCN (X ＝halogen) which required the use of the molecular halogen as coreagent. N-Thiocyanatosuccinimide, generated in situ from N-halosuccinimide and an inorganic thiocyanate, was also employed as an electrophilic reagent in the aromatic thiocyanation [17,18] and ring-expansion substitution reactions of 1,3-dithiolanes and 1,3-dithianes. [19] To the best of our knowledge, only limited substrates were investigated for the aromatic thiocyanation using N-thiocyanatosuccinimide.…”

Environment-Friendly Protocol for the Chlorination of Imidazoheterocycles by Chloramine-T

“…3-Chloro-8-methyl-2-phenylimidazo[1,2- a ]pyridine ( 2a ) was found to be a good substrate for traditional Pd-catalyzed cross-coupling reactions affording 8-methyl-2,3-diphenylimidazo[1,2- a ]pyridine ( 6a ) in 70% yield (Scheme 8, eq A). 54 More importantly, Cl in 2a could be easily replaced to construct the C–SCN bond in the presence of NaSCN furnishing 66% yield of 8-methyl-2-phenyl-3-thiocyanatoimidazo[1,2- a ]pyridine ( 6b ) (Scheme 8, eq B), 15 which belongs to an important synthetic intermediate for making biologically active molecules.…”

“…3,4 As a consequence, different processes have been reported for the synthesis and functionalization of imidazopyridine derivatives. 5−15 Many efficient methods of important functionalization and various synthetic strategies of imidazo[1,2- a ]pyridines from readily available starting materials have been also developed by our group. 16−27 Diverse substitutions at 3-position of imidazo[1,2- a ]pyridines induce different pharmaceutical properties.…”

Sustainable Synthetic Approaches Involving Thiocyanation and Sulfur- Cyanation: An Update

“…A recent publication described the regioselective introduction of thiocyanate function in the 5position of uracyls (Scheme 4) [4]. The method consists of the copper-catalyzed direct C-H thiocyanation of uracils (5) using ammonium thiocyanate and is applicable to a broad range of substrates, leading to 5-substituted uracil thiocyanates (6) in moderate to excellent yields. The proposed reaction mechanism involves a radical pathway.…”