Hantzsch pyridine synthesis

These compounds are an important class of calcium channel blockers[2] and as such commercialized in for instance nifedipine, amlodipine or nimodipine.

Previous studies have tested the reactions of preformed intermediates to determine the most likely mechanism and design successful syntheses.

Using condensation of benzaldehyde, ethyl acetoacetate and ammonium acetate as a model, experiments have proven that when catalyzed by p-toluenesulfonic acid (PTSA) under ultrasonic irradiation, the reaction can have a product yield of 96% in aqueous (SDS, 0.1M).

[14] Upon metabolism, 1,4-DHP based antihypertensive drugs undergo oxidation by way of cytochrome P-450 in the liver and are thus converted to their pyridine derivatives.

[11] As a result, particular attention has been paid to the aromatization of 1,4-DHPs as a means to understand biological systems and so as to develop new methods of accessing pyridines.

Additionally, this catalyst lead to a high yield at room temperature, reducing the impact of heating the reaction for an extended time.

A second study used ceric ammonium nitrate (CAN) as an alternate catalyst and achieved a solvent-free room temperature reaction.