Solid-state silica gel-catalyzed synthesis of fluorescent polysubstituted 1,4- and 1,2-dihydropyridines

Abstract

We present the green, highly atom-economical, solid-state silica gel-catalyzed synthesis of polysubstituted 1,4- and 1,2-dihydropyridines (DHPs) from commercially available materials, amines and ethyl propiolate. The DHP skeleton was assembled by heating the reactants and silica gel in a closed vessel. Aliphatic amines provided 1,4-isomers as the main or only DHP products, but the reactions of aromatic amines yielded a mixture of 1,4- and 1,2-isomers. To the best of our knowledge, this is the first example of the formation of a 1,2-DHP structure by the reaction of an amine with propiolic ester. Addition of 1 mass percent of H₂SO₄ to silica gel shifted the product distribution to 1,4-DHP as the main or the only isomer obtained. Experimental and theoretical analyses led to the identification of two key intermediates en route to DHPs and the explanation of the observed regioisomeric ratios. 1,2-DHPs show blue-cyan fluorescence in MeOH with the quantum yield Φ = 0.10–0.22 relative to quinine sulfate Φ = 0.58 and 1,4-DHPs show blue-violet fluorescence with Φ = 0.09–0.81.