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

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 phi = 0.10-0.22 relative to quinine sulfate phi = 0.58 and 1,4-DHPs show blue-violet fluorescence with phi = 0.09-0.81.

Automated summary

We developed a green and atom-economical method using solid-state silica gel catalysis for the synthesis of polysubstituted 1,4- and 1,2-dihydropyridines (DHPs) from commercially available materials, amines, and ethyl propiolate. By heating the reactants and silica gel in a closed vessel, the DHP skeleton was assembled. Aliphatic amines predominantly produced 1,4-isomers of DHPs, while reactions with aromatic amines yielded a mixture of 1,4- and 1,2-isomers. Addition of 1% mass percent of H2SO4 to silica gel shifted the product distribution towards 1,4-DHPs.