The structure of hydantoins in solution and in the solid state

Abstract

The results of NMR spectroscopic and X-ray crystallographic studies are critically discussed with respect to the structure of hydantoins, their tautomerism, and their acidity. The imide NH proton of the preferred, nearly planar 2,4-imidazolidine-dione tautomer proved to be more acidic than the corresponding amide NH proton. Phenyl substituents at the ring nitrogen atoms and at C-5 are twisted from the plane of the hydantoin ring; in case of ortho substituents restricted rotation about the N-aryl bond was found and the barrier to rotation determined by dynamic NMR spectroscopy.For 5-benzyl substituents, a folded conformation of the two rings, due to intramolecular interactions, was found and for 5-exo-methylene substituted hydantoins the relevant E/Z isomerism at the exo-cyclic C, C double bond was studied. In addition, the IH and 13C chemical shifts of the hydantoins proved to excellently indicate the electronic distribution along the hydantoin ring moiety. Finally, the mass spectrometric fragmentation of the hydantoins is critically discussed.

Experimental and computational study of the energetics of hydantoin and 2-thiohydantoin

“…This imidazolidine structure is present in a wide range of biologically active compounds with important applications in medicinal fields, such as antitumor [1] and anti-arrhythmic agents [2], anti-cancer drugs [3] having also agrochemical applications (bactericides and fungicides) [4]. Therefore, the knowledge of the physico-chemical properties of this type of compounds is important, particularly those properties that are related with their reactivity.…”

Study on the Synthesis, Characterization and Bioactivities of 3-Methyl-9’-fluorenespiro-5-hydantoin

“…Strukturo substituiranega fluorenilspirohidantoinskega derivata smo potrdili z UV-Vis, FT-IR, Ramansko, 1 H NMR in 13 C NMR spektroskopijo kot tudi s kombinacijo 2D NMR eksperimentov, ki so vklju~evali …”

“…1 Several compounds of this class have shown a pharmaceutically useful activity that led in some cases to clinical applications. In particular, 5-substituted and 5,5-disubstituted hydantoins are important medicinal compounds: phenytoin, or 5,5-diphenylhydantoin, is widely used as an anticonvulsant agent, for the treatment of epilepsy, and as a cardiac antiarrhytmic agents.…”

Use of 2-(1-(4-Bromophenyl) Ethylidene)hydrazinecarbothioamide and 2-(5-Chloro-2-Oxoindolin-3-Ylidene)hydrazinecarbothioamide in the Syntheses of 2-Thiohydantoin, Pyrimidine Derivatives: Evaluation of Their Antimicrobial Activities.

“…Res. 5(10), 1716-1725 1717 fungicides) [12]. Thiohydantoins are known for their uses as hypolipidemic [13] and antimutagenic [14].…”