1,2,4-Triazole is a privileged scaffold in medicinal and agricultural chemistry. Many useful and structurally diverse compounds have been prepared using 5-amino-1,2,4-triazoles as building block. Herein, we report a new microwave-assisted synthesis of 3-(5-amino-1H-1,2,4-triazol-3-yl)propanamides via two complementary approaches. The first approach involved the initial preparation of N-guanidinosuccinimide, which then reacted with amines under microwave irradiation affording corresponding 3-(5-amino-1H-1,2,4-triazol-3-yl)propanamides. The desired products were successfully obtained in the reaction with aliphatic amines (primary and secondary) via a nucleophilic opening of the succinimide ring and the subsequent recyclization affording the 1,2,4-triazole ring. This approach failed when less nucleophilic aromatic amines were used. Therefore, we designed an alternative pathway with the initial preparation of N-arylsuccinimides and their subsequent reaction with aminoguanidine hydrochloride under microwave irradiation. In this case, the 1,2,4-triazole ring closure was most efficiently achieved in the presence of organic base. These two approaches complement each other allowing preparation of a diverse library of 3-(5-amino-1H-1,2,4-triazol-3-yl)propanamides.
Previous Article in event
Ring Expansion Tetrahydropyrimidin-2-ones into Tetrahydro-1H-1,3-diazepin-2-ones: a Theoretical StudyPrevious Article in session
Next Article in event Next Article in session
A microwave-assisted synthesis of 3-(5-amino-1H-1,2,4-triazol-3-yl)propanamides from succinimides
Published: 03 November 2017 by MDPI in The 21st International Electronic Conference on Synthetic Organic Chemistry session Symposium on Microwave Assisted Synthesis
Keywords: triazole, microwave-assisted synthesis, 5-amino-1,2,4-triazoles, guanidinosuccinimides, arylsuccinimides