Hypervalent Iodine Mediated Efficient Solvent-Free Regioselective Halogenation and Thiocyanation of Fused N-Heterocycles

Abstract

A facile, rapid, metal-free regioselective halogenation and thiocyanation of imidazo[1,2-a]pyridine/pyrimidine heterocycles has been achieved under solvent-free reaction conditions. Halogenations and thiocyanation of the heterocycles could be accomplished by simple grinding of reactants and hypervalent iodine reagents with the corresponding alkali metal or ammonium salts. The method has been extrapolated to a cleaner synthesis of brominated imidazo[1,2-a]pyridine/pyrimidine derivatives, starting from the corresponding heterocyclic amines and substituted α-bromoketones, utilising HBr generated in situ as the source of bromine.

Photoelectrocyclization Reactions of Conjugated Cycloalkenones: Scope and Reactivity

“…To a pressure tube charged with bromide 48 (95.0 mg, 0.348 mmol), boronate ester 38 (123 mg, 0.522 mmol), dioxane (2.4 mL), and H 2 O (0.6 mL) that had been purged with N 2 gas for 10 min were added K 2 CO 3 (120 mg, 0.87 mmol), XPhos (9.9 mg, 0.021 mmol), and PdXPhos G2 (8.1 mg, 0.010 mmol). The reaction mixture was heated to reflux and stirred at that temperature overnight and then cooled to rt, diluted with ethyl acetate (20 mL), and filtered through a pad of silica gel.…”

Hypervalent iodine-mediated synthesis and late-stage functionalization of heterocycles

“…Further, Indukuri et al devised a regioselective protocol for the C-3 halogenation/thiocyanation of imidazo[1,2-a]pyridines/pyrimidine 400 by grinding with alkali metal/ammonium salts (M-X) mediated by PIDA 6 (Scheme 110). 141 This method enabled greener synthesis of halogenated/thiocyanated imidazoheterocycles 401 under solvent-free conditions. Reaction mechanism possibly involves in situ formation of [acetoxy(halo/thiocyanato)iodo]benzene from PIDA 6 and M-X, which serve as source of X + species facilitating electrophilic substitution on electron-rich substrates 400.…”

Recent Update on Transition Metal‐Free C(sp2)−H Bond Halogenation in (Hetero) Arenes

“…The method is applicable to a broad range of heterocycles including imidazoles, pyrazoles and indoles. TMSBr,DMSO [33] t BuONa,CBr 4, CCl 4 [79] PhSTMS or PhSSPh NXS [54] DMSO,NCS [60] Selectfluor,nitromethane [14] N-( i -Pr) 2 H 2 Cl DCDMH,NBS [53] PIDA,KBr,TFA [36] TrBF 4 ,NBS [35] (PhIO) n ,AlX 3 [55] SOCl 2 /Na 2 CO 3 [59] Triphosgine,TBAB/KBr [37] RÀ X Electrolysis [77] NH 4 Br,Electrolysis [78] LiCl,LiBr, Selectfluor [80] PhI(OAc) 2, halidesource [98] K 2 S 2 O 8 or oxone,NaX [99,100] DCDMH/DBDMH 450 nm LED [89] I 2 /TBHP [68] Scheme 83. Site-selective CÀ H halogenation (Br/I) with sodium bromide and sodium iodide with N-fluorobenzenesulfonimide as an oxidant.…”

“…Alla et al demonstrated [98] a solvent-free strategy to effect regioselective CÀ H halogenation as well as pseudohalogenation in imidazopyridines and other such N-fused heterocycles using iodobenzenediacetate as the oxidizing agent and alkali halides or ammonium halides or aqueous HBr/aqueous HCl solution as the halogen source.Adimurthy et al developed [99] a potassium peroxodisulfate or oxone mediated methodology using sodium salts of halides as the halogen source. Katrun and Kuhakarn also independently developed [100] a similar halogenation strategy for 2-arylimidazo [1,2-a]pyridine systems.…”