Mild and Sustainable Synthesis of Chromene Dimers Through Amidine and Flexible Diamine Linkers

Chromene derivatives are important structural motifs in biologically active compounds and functional materials, and the development of efficient strategies for their synthesis remains of considerable interest. In this work, simple and sustainable methodologies were developed for the synthesis of chromene dimers linked through short amidine/geminal diamine spacers or long, flexible alkyl diamine linkers. The amidine and geminal diamine linkers were obtained from 3-aminochromene derivatives via nucleophilic addition of the amino group to triethyl orthoformate or non-phenolic aldehydes in ethanol, at room temperature or under reflux, affording the corresponding dimers in moderate to very good yields. In a complementary approach, flexible alkyl diamide linkers were prepared from diamines and ethyl cyanoacetate, followed by condensation with salicylaldehydes in aqueous hydrogen carbonate solution and subsequent acidic hydrolysis, leading to new chromene dimers in excellent yields. These mild and operationally simple protocols provide efficient access to structurally diverse chromene dimers with potential applications in medicinal chemistry and materials science.