One-pot, microwave-assisted synthesis of polymethylene-bridged bis(1H-1,2,4-triazol-5(3)-amines) and their tautomerism

Abstract

A highly selective and efficient method for the synthesis of 3,3'(5,5')-polymethylene-bis(1H-1,2,4-triazol-5(3)-amines) was developed using the reaction of dicarboxylic acids and aminoguanidine in an aqueous medium. This one-pot, microwave-promoted method was proved to be scalable affording the desired products in good yields and purity. The scope of the method was successfully explored by the preparation of a small library of polymethylene-bis(1H-1,2,4triazol-5(3)-amines) with different alkyl chain linkers. The annular prototropic tautomerism in the prepared compounds was studied using NMR spectroscopy and X-ray crystallography.

Crystal structure of 3-(5-amino-1H-1,2,4-triazol-3-yl)-1-(piperidin-1-yl)propan-1-one, C10H17N5O

“…the shortening of the C1-N3 [ The observed tautomer is as expected based on literature precedents [8]. However, a compound was recently identified crystallizing with a hydrogen located at the nitrogen atom furthest away from the amino group, that is, existing in the form of the 3-amino-1H-tautomer [9]. It is also noted that an example of a crystal comprising both 5-amino-1H-and 3-amino-1H-tautomers, co-existing in equal proportions, has also been reported [10].…”

Annular Tautomerism of 3(5)-Disubstituted-1H-pyrazoles with Ester and Amide Groups

“…Pyrazole is a five-membered aromatic heterocycle with two adjacent nitrogen atoms, classified as azole. Pyrazole derivatives have broad application, from engineering and polymers [1,2,3,4,5,6,7,8], to biological activity [9]; thus, new synthetic strategies are constantly developed [10,11,12,13,14,15,16,17]. Among them, there are 1 H -pyrazoles with substituents at positions 3 and 5, which reveal interesting applications [18,19,20,21,22,23,24,25], and some of them are depicted in Figure 1.…”

The Riveting Chemistry of Poly‐aza‐heterocycles Employing Microwave Technique: A Decade Review

“…Moreover, aminoguanidine hydrochloride ( 11 ) with carboxylic acids efficiently resulted poly‐methylene‐bridged 1,2,4‐triazol‐5‐amines 12 under microwave in aqueous medium (Scheme 4). [10b] …”