Reaction of Unsaturated Meldrum’s Acid Derivatives with Azide Ions

Abstract

The reactions of unsaturated Meldrum’s acid derivatives with azide ions were studied. The selectivity and reaction pathways were determined for two types of substrates, namely enyne and spirocyclopropane derivatives. The enyne derivative undergoes regioselective Huisgen 1,3-dipolar cycloaddition to form a 1,2,3-triazole, while the trimethylsilyl group remains intact, providing opportunities for subsequent modification of the molecule. In contrast, the spirocyclopropane derivative does not undergo cycloaddition but reacts through nucleophilic opening of the strained three-membered ring to form an organic azide. The structures of all the compounds obtained were confirmed using a combination of spectroscopic methods, including NMR spectroscopy, and elemental analysis. The thermal stability of the synthesized azide was assessed using simultaneous thermogravimetric and differential thermal analysis. The low enthalpy of decomposition indicates that this azide is not an explosive compound. The cytotoxicity of the compounds obtained toward human stromal, lung carcinoma, and melanoma cell lines was evaluated using the MTT assay. The cells remained completely viable at a concentration of 50 μM, indicating the absence of toxic effects under these conditions. A fundamental difference was found between the reactivities of activated unsaturated moieties in Meldrum’s acid derivatives. The developed approaches can be used to obtain new triazole and azide structures of interest as synthons for medicinal chemistry and materials science. The results contribute to the development of methods for selective transformations of highly reactive carbocyclic systems and expand the range of tools available for designing biologically active molecules and functional materials.