Mechanochemical Preparation of 3,5-Disubstituted Hydantoins from Dipeptides and Unsymmetrical Ureas of Amino Acid Derivatives

Abstract

5-Substituted-3-(alkoxycarbonyl)alkyl-hydantoin derivatives were prepared by mechanochemistry from amino esters or dipeptides, via a 1,1'-carbonyldiimidazole-mediated one-pot/two-step cyclization reaction involving amino acid unsymmetrical urea A and carboxy-imidazolyl-dipeptide ester B intermediates. Comparative experiments in solution were also performed. The successful preparation of an antibacterial agent precursor was also investigated.

Mechanochemistry for “no solvent, no base” preparation of hydantoin-based active pharmaceutical ingredients: nitrofurantoin and dantrolene

“…It is worth noting that, coherently with our previous findings in other mechanochemical activated transformations, 10,33 the strong activation provided by mechanochemical shocks avoided the use of base to generate a more nucleophilic amine. Moreover, two semi-batch large scale experiments were also performed under different mechanical stress in a planetary ball mill (13.2 mmoll) or a SPEX mill (6.6 mmol) ( Table 1).…”

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

“…This has led groups of synthetic and medicinal chemists to explore the synthetic methods to access these valuable molecules, as well as looking for more sustainable alternatives to the previously existing procedures. 528 The different families of molecules, i.e., substituted hydantoins at positions C-5, N-1, and N-3, alkyl/ arylidene, spiro, polycyclic, and amino hydantoins, contribute to the extended variety of biomedical applications that have already been assessed or that will be with the future discovery or design of novel structures. The latter as well as further exploration of the potential medicinal and pharmaceutical relevance of hydantoinic compounds represent the future directions and challenges of the field.…”

New spirohydantoins derived from β-tetralone: Design, synthesis and evaluation of their pharmacokinetically relevant propertie

“…Bela kristalna supstanca; Prinos: 62 %; t.t. 163−165 °C; IR (KBr, ν/cm -1 ): 3296 (NH), 1769 (C=O), 1708 (C=O); 1…”

“…Bela kristalna supstanca; Prinos: 70 %; t.t. 189−190 °C; IR (KBr, ν/cm -1 ): 3255 (NH), 1770 (C=O), 1719 (C=O); 1 Vrednosti talasnih dužina koje potiču od apsorpcionih maksimuma niže energije prikazane su u tabeli 1, a reprezentativni spektri snimljeni u etanolu, predstavljeni su na slici 2. [4.5]dekan-2,4-diona u odabranom setu rastvarača.…”