Chitosan as a solid catalyst for the one-pot Knoevenagel condensation in the context of sustainable chemistry

Abstract

We employed chitosan to catalyse the Knoevenagel condensation between various benzaldehydes and ethyl cyanoacetate. Chitosan exhibited excellent reusability, maintaining catalytic efficiency over six reaction cycles with yields consistently between 95% and 98%, for benzaldehyde and p-tolualdehyde. Furthermore, we were able to recycle the used solvent (ethanol), enhancing overall sustainability. Expanding the application of chitosan, we synthesised 4-methyl-3-oxo-N-phenyl-2-(phenylmethylene)pentanamide, a key intermediate of the statin drug Atorvastatin synthesis on gram-scale with 96% yield. This demonstrates the use of chitosan as a catalyst for the synthesis of fine chemicals with improved sustainability; notably, the chitosan-catalysed process aligns with several key principles of sustainability. The employed chitosan exhibited a high water-binding capacity of about 520%, which enhances product formation by capturing water as the reaction byproduct. The high yields in the repeated use originated from the catalytic action of a large number of amino groups and the extraordinary and reversible swelling and binding capacity for polar solvents. We propose that such a swellable, insoluble, abundant catalyst material that is able to bind large amounts of water, constitutes a promising concept in organocatalysis. Analytical techniques such as scanning electron microscopy, mercury intrusion porosimetry, diffuse reflectance infrared Fourier transform spectroscopy, and X-ray diffraction analysis verified the catalyst's integrity, showing no significant physical or chemical degradation after multiple uses. Thus, chitosan emerges as a sustainable catalyst for organic synthesis with promising implications for Knoevenagel reactions.