Synthesis and Unusual Reactivity of Dipropargyl Ester Derivatives of Imidazole-4,5-dicarboxylic Acid in Menshutkin and CuAAC Reactions

In the present work, a series of propargyl esters based on imidazole-4,5-dicarboxylic acid was obtained for the first time and their reactivity in the Menshutkin reaction was studied. The possibility of further modification of the obtained imidazolium salts under the conditions of the azide-alkyne cycloaddition reaction catalyzed by copper was also studied. Using high-resolution mass spectrometry with electrospray ionization (HRMS ESI), it was found that in the Menshitkin reaction of propargyl esters with alkyl iodides, by-products of the nucleophilic attack of the iodide ion on the N-alkyl fragment are formed, which are not observed when using alkyl tosylates. It was found that when the obtained salts were introduced into the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, a side process occurred. The process consisted of a nucleophilic attack of triethylamine on the –OCH₂– fragments of propargyl carboxylate or triazolemethylene carboxylate, followed by decarboxylation of the resulting carbenobetaine, which was confirmed by the HRMS ESI. It was found that the azide-alkyne cycloaddition in the studied salts can be carried out without side products in the presence of sodium ascorbate as a copper base/stabilizer. For propargyl-containing mono- and bisimidazolium salts, the aggregation characteristics (critical aggregation concentration (CAC) and size of the resulting aggregates) in aqueous media were established. A decrease in CAC and compaction of aggregates were found for more lipophilic tetradecyl derivatives and upon going from mono- to bisimidazolium salts.