Synthesis and dynamic NMR study of spiroheterocycles containing a 1,2,4-triazolidine moiety

Abstract

A one-pot synthesis of spiro-heterocyclic systems containing a 1,2,4-triazolidine moiety via 1,3-dipolar cycloaddition reaction of azomethine ylides (generated in situ from α-amino acids and ninhydrin) with diisopropyl azodicarboxylate in 50% aqueous MeOH at room temperature, is described. The structure of a typical product was confirmed by X-ray crystallography. The 1H NMR spectra of diisopropyl 1,3-dioxo-1,3-dihydrospiro[indene-2,3′-[1,2,4]triazolidine]-1′,2′-dicarboxylate exhibited dynamic NMR effects, which were attributed to the fast positional change of the ester groups and their interaction with N–H as well as with methylene protons, and restricted bond rotation of the carbamate groups. The calculated free-energy of activation (ΔG#) for these dynamic processes are 64 ± 2 kJ mol−1 and 55 ± 2 kJ mol−1, respectively.