Reactions of 5-aryl-4-acyl-1-(4-hydroxyphenyl)-3-hydroxy-3-pyrroline-2-ones with butylamine, hydroxylamine, and semicarbazide

Design of Drug‐Like Protein–Protein Interaction Stabilizers Guided By Chelation‐Controlled Bioactive Conformation Stabilization

“…Reaction of rac ‐ 2 with aqueous ammonia in acetic acid under microwave heating afforded only vinylogous amide rac ‐ 6 in 20 % yield, with no rac ‐ 9 observed (Scheme ). This contrasts with literature reports that 4‐aroyl substituents favor regiospecific endocyclic nucleophilic attack by sterically unencumbered amines to afford the regioisomers corresponding to 9 . Reaction of rac ‐ 2 with p ‐methoxybenzylamine under microwave heating afforded rac ‐ 7 (6 %) and rac ‐ 8 (26 %).…”

“…This contrasts with literature reports that 4-aroyl substituents favor regiospecific endocyclic nucleophilic attack by sterically unencumbered amines to afford the regioisomers corresponding to 9. [35][36][37][38][39][40] Reaction of rac-2 with p-methoxybenzylamine under microwave heating afforded rac-7 (6%) and rac-8 (26%). Removal of the PMB group of rac-8 using TFA afforded rac-9 in 53% yield.…”

Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones

“…The reaction between 1,5-diphenyl-4-acetyl-3-hydroxy-3-pyrrolin-2-one ( 4a ) and 4-methoxybenzylamine ( 9a ) was chosen to optimize the reaction conditions, such as the reactant ratio and solvent. Heating 2-pyrrolidinone derivative 4a (1 equiv) and aliphatic amine 9a (2.5 equiv) in glacial acetic acid [ 42 ] resulted in the formation of product 10aa with a yield of only 36%. It is clear that compound 9a could be protonated in the acidic environment, decreasing its nucleophilicity and therefore, product 10aa was obtained in low yield.…”

“…These 2-pyrrolidinone derivatives were then reacted with aliphatic amines in ethanol to obtain a library of 1,4,5-trisubstituted pyrrolidine-2,3-dione enamine derivatives. As compared to glacial acetic acid [ 42 ], ethanol has showed to be the best solvent for the synthesis of these pyrrolidine-2,3-diones and a dramatic increase in the yield of the desired products was also observed. In addition, understanding of the reaction mechanism at the molecular level brings an efficient evaluation and good orientation in experimental work [ 43 ].…”

“…In addition, the resulting 2-pyrrolidinone derivatives also showed antibacterial and antifungal activities [39][40][41]. The presence of an acyl group at the 4-position enables these heterocycles to be functionalized via nucleophilic addition reactions between the carbonyl group and nucleophiles like hydroxylamine and semicarbazide [42].…”