Design of a bifunctional TEMPO-tertiary amine mesoporous silica catalyst for the three-step cascade synthesis of a chromene derivative

ABSTR A C T A key challenge is design of materials and processes whereby competing reagents or conditions do not harm the multi-step sequence, thus allowing for more efficient chemical synthesis with elimination of work-up and sep-aration steps. In this work, a three-step reaction cascade is performed using a porous bifunctional dimethylpropylamine-TEMPO-MCM41 catalyst, converting the commodity chemicals benzyl alcohol, sodium hypochlorite, and malononitrile to a biologically active anti-cancer, and anti-malarial 2-amino-chromene de-rivative. The cascade first utilizes a TEMPO-catalyzed oxidation of benzyl alcohol to benzaldehyde with NaOCl as the terminal oxidant. This is followed by a two-step, dual base catalyzed Knoevenagel condensation with malononitrile followed by a Michael addition with lawsone. Optimal conditions converting benzyl alcohol to 2-amino-5,10-dioxo-4-phenyl-5,10-dihydro-4H-benzo[g]chromene-3-carbonitrile include the delayed addition of malononitrile and lawsone during the three-step reaction sequence, which results in a 2-amino-chromene yield of over 80%. The importance of stepwise reagent addition is rationalized due to the unfavorable adsorption of acidic lawsone on the surface-grafted base catalyst. Tertiary Bronsted base sites of dimethylpropylamine outperform the more Lewis basic primary propylamine functionalized catalyst. This work outlines a simple and effective method for generating mesoporous materials with two types of active sites via co-condensation and thiol-ene coupling procedures.

Automated summary

The study involved performing a three-step reaction cascade converting benzyl alcohol, sodium hypochlorite and malononitrile to a biologically active derivative with a yield above 80%. By optimizing the reaction conditions through stepwise reagent addition, the researchers successfully demonstrated a simple and effective method for generating mesoporous materials with two types of active sites.