A rapid and efficient ultrasound-assisted synthesis of 5,5-diphenylhydantoins and 5,5-diphenyl-2-thiohydantoins

Abstract

To obtain a rapid, efficient and mild synthesis of 5,5-diphenylhydantoin and 5,5-diphenyl-2-thiohydantoin derivatives, ultrasonic irradiation has been applied to the reaction mixtures containing substituted benzils and urea or thiourea derivatives catalyzed by KOH in DMSO/H(2)O, which allowed us to achieve products at room temperature in a good yield and short time without any side product. This convenient procedure will allow a further increase of the diversity within the hydantoin family.

Antioxidant and Antimicrobial Activities of Some Novel 2-Thiohydantoin Derivatives

“…In addition, the increasing of fungal infections with limited therapeutic treatment, leads to discover novel antifungal drugs via set new approaches to target the chemical matter [4]. Recently, efficient methods for the preparation of thiohydantoin derivatives, other than the conventional multi-step methods were investigated [5,6]. The 2-thioxoimidazolidin-4-ones or 2-thiohydantoins are five-member heterocyclic systems with very reactive nuclei and cyclic thiourea cores [7].…”

Mechanochemical Preparation of Hydantoins from Amino Esters: Application to the Synthesis of the Antiepileptic Drug Phenytoin

“…Trimethylsilyl-isocyanate (TMS-NCO) and chlorosulfonyl-isocyanate are alternatives to cyanate salts for the preparation of 1,3-unsubstituted hydantoins. , Recently, our group has described the solid-phase synthesis of 5-substituted hydantoins under microwave-irradiation from supported amino acids and isocyanates . The condensation of benzil and urea in excess according to Biltz reaction ,, remains the main pathway to the obtention of 5,5-disubstituted hydantoins and was historically used for the synthesis of the antiepileptic drug phenytoin. , Several improvements were described using enabling technologies such as ultrasonication, , heating via microwave irradiation (in solution or neat − ), in polar solvents [water, poly(ethylene glycol) or DMSO] or grinding the reactants (with mortar and pestle) . In view of the REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) legislation, regulating chemical substances and directed to both the protection of the human health and the environment from the risks of potentially toxic chemicals, the use of certain chemicals will be phased out, affecting industries throughout the world.…”

Recent Advances in the Synthesis of Hydantoins: The State of the Art of a Valuable Scaffold

“…Recently, many advances were brought to the original procedure. Indeed, novel conditions were reported, using heterogeneous catalysts , or modern technologies such as microwave irradiation , or ultrasonication. − Solvent-free procedures were also developed and notably one solvent-free route in which a mixture of benzil, urea, and NaOH were ground with a mortar and a pestle . However, this method was found to be not applicable to ball-milling technology, and phenytoin was obtained by the Read procedure using activated trimethylsylilisocyanate (Scheme ).…”