A Straightforward, One-Pot Protocol for the Synthesis of Fused 3-Aminotriazoles

Abstract

A simple protocol for the synthesis of 3-amino-[1,2,4]triazolo[4,3-a]pyridines is reported. The newly developed one-pot methodology involves the reaction of hydrazinopyridine with isothiocyanates to give the corresponding thiosemicarbazides, which are further desulfurized in situ using polymer-supported Mukaiyama's reagent to promote the final cyclization and formation of the central core. Aryl isothiocyanates bearing both electron-donating and electron-withdrawing groups are well tolerated, and the expected compounds were obtained in excellent purities and yields after removal of salts with a SPE-NH2 column. This methodology proved to be robust in the extension to 3-amino-[1,2,4]triazolo[4,3-a]-pyrazines and 3-amino-[1,2,4]triazolo[4,3-c]-pyrimidines, and no significant differences were noticed in terms of purities and yields. The straightforward protocol developed, mix, filter, and evaporate, is appropriate for performing multiple reactions in parallel fashion without need of purification.

Oxidative cyclization of 1-(pyridin-2-yl)guanidine derivatives: a synthesis of [1,2,4]triazolo[1,5-a]pyridin-2-amines and an unexpected synthesis of [1,2,4]triazolo[4,3-a]pyridin-3-amines

“…16 The structures of 3c and 7c obtained in this one-pot oxidative cyclization were confirmed by comparing the spectral data with that of 3c and 7c prepared according to known procedures (Scheme 4). 8,17 In the case of 1-(5-chloropyridin-2-yl)guanidine 5d, compound 7d was obtained as the main product in 50% yield with a trace amount of 3d (entry 3). Then 1-(pyridin-2-yl)guanidines bearing a CF 3 group at three different positions were subjected to the reaction.…”

A Convenient One‐pot Synthesis of N‐Fused 1,2,4‐Triazoles via Oxidative Cyclization Using Trichloroisocyanuric Acid

“…The described oxidative cyclization has previously been reported for the preparation of triazoloquinoxalines . Other methods reported in the literature for the cyclization of the triazole ring usually require a combination of N ‐bromosuccinimide and base , refluxing orthoesters , acids , desulfurization of thiosemicarbazides , or cyclization of hydrazides in polyphosphoric acid . A couple of examples of oxidative cyclizations using chloramine‐T have previously been reported .…”

Highly Efficient Synthesis of 4,3‐Fused 1,2,4‐Triazoles via One‐Pot Multicomponent Domino Reaction Catalyzed by KI/TBHP

“…Several methods were known from the literature to synthesize [1, 2,4]triazolo[4, 3‐ a ]pyridines which include (Scheme ): a) 1,3‐dipolar cycloaddition of N ‐tosylhydrazones with aromatic N ‐heterocycles by I 2 /TBHP and iodosobenzene (PhIO); b) oxidative cyclization of 2‐pyridylhydrazones by RuCl 3 /Oxone, ceric ammonium nitrate (CAN), chloramine T, N ‐bromosuccinimide (NBS), CuCl 2, CuBr 2 /Oxone ; and oxidants such as hypervalent iodine reagents; c) reaction of 2‐pyridylhydrazines with aldehydes in the presence of I 2 /K 2 CO 3 ; with carboxylic acids in the presence of polystyrene‐bound triphenylphosphine (PS‐PPh 3 )/CCl 3 CN, 1,1′‐carbonyldiimidazole (CDI); and POCl 3 /PCl 5 ; with isothiocyanates promoted by Mukaiyama's reagent; or involving [Mo(CO) 6 ]‐mediated carbonylation of aryl iodides; and d) thermal cyclization of 2‐pyridylhydrazides by using Lawesson's reagent or in acetic acid under microwave irradiation …”