Efficient and Aqoues Synthesis of 3,4-Disubstituted Isoxazol-5(4H)-one Derivatives Using Piperazine under Green Conditions

Abstract

The one-pot, three-component, as well as expeditious synthesis of 3,4-disubstitted isoxazol-5(4H)-ones has been attained from the heterocyclization of various aryl/heteroaryl aldehydes, active methylene compounds, and hydroxylamine hydrochloride in the presence of piperazine as the efficient, low-cost, commercially available, and eco-friendliness basic organocatalyst. This double secondary amine catalyst was found that catalyzed the synthesis of isoxazol-5(4H)-ones under green conditions. The additional features of the present catalyst include readily available starting materials, relatively low catalyst loading, using water as a green solvent, broad substrate scope, simplicity, good to excellent reaction yields, faster synthesis, and avoiding the hazardous organic solvents.The piperazine is a special secondary heterocyclic diamine containing two nitrogen atoms at 1 and 4 positions, which present in pharmaceutical and biological active compounds. 1 Piperazine ranks as the third most common nitrogen heterocycle in drug discovery, 2 and it is an important pharmaceutical intermediate for the synthesis of anticancer, antituberculosis, antibacterial, antipsychotic, antimalarial, antioxidant, antihistamine, antidepressant, antifungal, and antidiabetic drug candidates. 3 This heterocyclic molecule acts as a transmitter of γ-aminobutyric acid receptor inhibitor, succinic acid formation by parasites inhibitor, 4 and a promoter for CO2 absorption. 5 Piperazine citrate organosalt as a derivative of piperazine is also used in the treatment, control, and prevention of several worm infections as threadworm, roundworm and pinworm in both human and animals. It is also helps in the treatment of chicken naturally infected with gastrointestinal helminths and can be used in the treatment of ascaris lumbricoides infestation and bacterial infections. 6 Literature survey