Towards heterogeneous green catalysis for Aza-Michael reactions

Abstract

Aza-Michael addition of amines has played an influential role in the pharmaceutical industry because products of such reactions serve as synthetic intermediates for other biologically active molecules. Catalysts implemented for aza-Michael reactions suffer drawbacks, including side-product formation and difficult product extractions, which thus further contribute to the generation of environmentally unfriendly chemical waste. The scope of this research was to find a heterogeneous catalyst that can efficiently promote aza-Michael synthesis under the guidelines of green chemistry. Starting with an assortment of heterogeneous acidic catalysts, each one was tested for double aza-Michael addition. Silica-supported polyphosphoric acid (PPA/SiO) catalyst seemed to be the most promising. Therefore it was introduced to different combinations of reaction temperature, substrates stoichiometry and catalyst loading for the purpose of finding the most optimal conditions. Optimization trials were later repeated for secondary amine mono-addition. Under the determined reaction conditions, PP A/Si07 was found to enhance the versatility of aza-Michael addition by successfully incorporating a structurally diverse collection of amines. Substrate scope was extended to a,B-unsaturated esters, acrylonitrile and 2-propenamide as Michael acceptors to give products in good to excellent yields. All isolated products were successfully characterized using infra-red spectroscopy, nuclear magnetic resonance spectroscopy and mass spectrometry. The selected catalyst was simple to prepare, stable under long-term storing and easy to separate from the products formed. In addition, PPA/Si02 catalysis did not require drastic reaction conditions such as refluxing temperatures to ensure near stoichiometric yields.