I₂/KI-Mediated Oxidative N–N Bond Formation for the Synthesis of 1,5-Fused 1,2,4-Triazoles from N-Aryl Amidines

Abstract

An I2/KI-mediated oxidative N-N bond formation reaction is described. This new and environmentally benign approach allows for the convenient synthesis of a variety of 1,2,4-triazolo[1,5-a]pyridines and other 1,5-fused 1,2,4-triazoles from readily available N-aryl amidines in an efficient and scalable fashion.

Synthesis of Novel Imidazo[1,2‐a]pyridin‐2‐amines from Arylamines and Nitriles via Sequential Addition and I2/KI‐Mediated Oxidative Cyclization

“…Previously,w ed isclosed an I 2 /KI-mediated oxidative NÀNb ond formation reactionf or the synthesis of 1,2,4-triazolo [1,5-a]pyri- Scheme1.Twop athways for the I 2 /KI-meditated oxidative cyclization of Naryl amidines 3. dines and relatedh eterocycles 4' from readily available N-aryl amidines 3 [10] (path a, Scheme1). However,u nder the previous oxidative cyclization conditions (I 2 /KI, K 2 CO 3 ,D MSO,1 00 8C), substrate 3a bearing ab enzylg roup at R 3 position resulted in no expected triazolopyridine (4a')a ta ll (Scheme 2).…”

CuI/I2‐Mediated Intramolecular Oxidative Cyclization Reaction of N‐(2‐pyridyl)amidines by the Direct Double C−H Functionalization of a C(sp3)−H Bond

“…However, it is noteworthy that when the substituents on the N ‐(2‐pyridyl)amidines are slightly different, even if the same oxidant was used, the intramolecular bonding modes to afford the corresponding products by C−H functionalization were diverse. For instance, in 2016, Chang's group published the synthesis of 2‐aminoimidazo[1,2‐α]‐pyridines through an I 2 /KI‐mediated intramolecular oxidative C−N bond formation of N ‐(2‐pyridyl)amidines (Scheme b), in which the bonding mode of the reaction was completely different from a previously reported one by Chang and co‐workers in 2015. Therefore, these surveys indicated clearly that the results of the reaction were greatly affected by the structure of the substrates and the reaction conditions.…”

“…In previous literature reports, as one of the most important N‐aryl amidines, N ‐(2‐pyridyl)amidines have also been employed for the synthesis of different nitrogen‐containing heterocyclic skeletons by using various oxidants by the C−H functionalization for N−N and C−N bond formation. For example, a literature survey indicated that when a large variety of oxidants were utilized, including air, PIFA (phenyliodine bis(trifluoroacetate)), NaClO, MnO 2 , Pb(OAc) 4 , and I 2 , 1,2,4‐triazoles with various substituents can be achieved by intramolecular oxidative N−N bond formation from N ‐(2‐pyridyl)amidines substrates (Scheme a). However, it is noteworthy that when the substituents on the N ‐(2‐pyridyl)amidines are slightly different, even if the same oxidant was used, the intramolecular bonding modes to afford the corresponding products by C−H functionalization were diverse.…”

Synthesis of 1,2,4‐Triazolo[4,3‐a]pyridines and Related Heterocycles by Sequential Condensation and Iodine‐Mediated Oxidative Cyclization

“…Previously, utilizing molecular iodine as the sole oxidant, we have successfully constructed nitrogen‐containing heterocyclic frameworks, such as pyrazoles, quinazolinones, and benzimidazoles, through oxidative C−N bond formation . Recently, we disclosed an I 2 ‐mediated oxidative cyclization reaction of N ‐aryl amidines 8 to prepare 1,5‐fused 1,2,4‐triazoles 9 . As a continuation of this research into the synthesis of fused 1,2,4‐triazoles, herein we envisioned a sequential synthetic method for the preparation of 1,2,4‐triazolo[4,3‐ a ]pyridines and related heterocycles through condensation of aryl hydrazines and aldehydes followed by iodine‐mediated oxidative cyclization.…”

“…[23] Recently,wedisclosed an I 2 -mediated oxidative cyclization reactiono fN-aryl amidines 8 to prepare 1,5-fused1 ,2,4triazoles 9. [24] As ac ontinuation of this research into the synthesis of fused 1,2,4-triazoles, herein we envisioned asequential synthetic method for the preparation of 1,2,4-triazolo[4, 3-a]pyridines and relatedh eterocycles through condensation of aryl hydrazines and aldehydes followed by iodine-mediated oxidative cyclization.…”