Synthesis of fused 3-amino-1,2,4-triazoles via sequential addition of aryl hydrazines to isothiocyanates and I 2 -mediated cyclodesulfurization

Access to 3-Amino-[1,2,4]-triazolo Pyridines and Related Heterocycles via Electrochemically Induced Desulfurative Cyclization

“…Among them, many compounds with [1,2,4]­triazolo pyridine core structures exhibit pharmacological and therapeutic effects, for example, as inhibitors of p38 for the treatment of chronic obstructive pulmonary disease, JAK2 inhibitors (CEP-33779) for anticancer therapy and GSK-3β inhibitors with potent neuroprotective effects . Owing to the attractive medical value of triazolo pyridines, their efficient synthesis and subsequent functionalization have attracted long-term attention. − One conventional approach for synthesizing [1,2,4]­triazolo pyridines is through the tandem coupling/cyclization of 2-hydrazino­pyridines with carboxylic acids. This reaction requires the addition of reagents such as POCl 3 /PCl 5 , iodobenzene­diacetate (IBD), and 1,1′-carbonyl­diimidazole (CDI) .…”

“…Swinnen’s group has disclosed a one-pot protocol for the synthesis of [1,2,4]­triazolo pyridines, involving the formation of thio­semicarbazides and subsequent in situ desulfurative cyclization promoted by polymer-supported Mukaiyama’s reagent, which avoids using highly toxic metal desulfurizing reagents . Several examples of iodine-mediated oxidative cyclization have been reported with stoichiometric amounts of molecular iodine as an oxidant . A microwave irradiation strategy involving the anion-mediated synthesis of 3-amino-[1,2,4]-triazolo­[4,3- a ]­pyridines from thio­semicarbazides is subsequently disclosed .…”

Cyclodesulfurization: An Enabling Protocol for Synthesis of Various Heterocycles

“…Similarly, Zhen et al ., converted thiourea derivatives 75 to their corresponding 2‐aminobenzimidazoles 76 in excellent yield using I 2 as desulfurizing agent (Scheme 15B) [66] . The same group published another approach to synthesize 3‐amino‐1,2,4‐triazole 78 by reacting hydrazinyl‐pyridine with isothiocyanates to yield thiosemicarbazides 77 in presence of I 2 /K 2 CO 3 system afforded the 78 (Scheme 15C) [67] . Electron withdrawing groups decreased the reactivity, further lowering the reaction yield.…”

Choline Chloride Based Deep Eutectic Solvents as a Tuneable Medium for Synthesis of Coumarinyl 1,2,4‐Triazoles: Effect of Solvent Type and Temperature

“…The ratio of 1,2,4-triazoles and thiosemicarbazides in reaction mixtures was determined by HPLC and 1 H NMR. [29] An effect of different solvents on the formation of triazoles from substituted hydrazines and isothiocyanates, followed by iodine mediated cyclization, was studied by Jiao et al [30] The type of the solvent greatly influenced the reaction rate and product yield, and ethanol was suggested as optimal for this type of reaction. Scheme 1.…”

“…[28] Azzouni et al synthesized 1,2,4-triazoles from acryloylimidates with hydrazines at room temperature in methanol, expanding the possibilities of introducing substituents in positions N(1), C(3) and C(5) of 1,2,4triazole ring. [29] An effect of different solvents on the formation of triazoles from substituted hydrazines and isothiocyanates, followed by iodine mediated cyclization, was studied by Jiao et al [30] The type of the solvent greatly influenced the reaction rate and product yield, and ethanol was suggested as optimal for this type of reaction. The influence of the solvent type on the formation of 1,2,4-triazoles from hydrazines and imides fol-lowed by filtration through Al 2 O 3 was also studied, where DMF was found to be the most convenient and alumina crucial for cyclization into the triazole ring system.…”