PhD Scientific Days 2023

Budapest, 22-23 June 2023

Pharmaceutical Sciences - Posters F

Kabachnik-Fields Reaction in Light of the Principles of Green Chemistry

Patrik Pollák1,2, Dóra Gábor1, Balázs Volk1, András Dancsó1, Gyula Simig1, Mátyás Milen1
1 Egis Pharmaceuticals Plc., Directorate of Drug Substance Development, P. O. Box 100, H-1475 Budapest, Hungary
2 Department of Organic Chemistry, Faculty of Pharmacy, Semmelweis University, Hőgyes Endre u. 7., H-1092 Budapest, Hungary

Text of the abstract

α-Aminophosphonic acids and α-aminophosphonates are important representatives of organophosphorus compounds. They possess a wide range of biological activities acting as enzyme inhibitors, antibiotics, anticancer agents, herbicides, and plant growth regulators.

A catalyst- and solvent-free room temperature method has been elaborated for the three-component (carbonyl compounds, primary or secondary amines and phosphites) Kabachnik−Fields synthesis of α-aminophosphonates.

Some parameters have been studied, that potentially influence the course of the reaction using benzaldehyde, aniline and diethyl phosphite. In order to extend the reaction under the new reaction conditions, then 3 series of experiments were carried out always varying one of the three reagents.

The method was extended with 42 product examples, including 5 new compounds. With a few exceptions, good yields were obtained (17-99%), although in some cases long reaction times were required.

In summary, we have demonstrated that the three-component Kabachnik–Fields reaction, carried out at room temperature under catalyst- and solvent-free conditions, is feasible with a broad structural scope. The described procedures satisfy the requirements of green chemistry and facilitate the synthesis of new α-aminophosphonates.

The research has been funded by Egis Pharmaceuticals PLC, Directorate of Drug Substance Development.