Exploring the environmentally benign synthesis of 2,4,5-trisubstituted-2-imidazoline derivatives

Abstract

2-imidazolines are an important class of heterocycles with a wide range of applications in various fields including biomedical science, pharmaceuticals and surfactant industry. Among the applications the most prominent is catalysis as the hydrolysis of 2,4,5-triarylimidazolines provide 1,2-diaryl-1,2-diaminoethanes, a significant ligand in the field. 2,4,5-triarylimidazolines can be prepared through the reaction of benzaldehyde and ammonia; however, the reported reactions usually require harsh conditions or toxic solvents such as DMF. This project proposes a sustainable synthetic route for the synthesis of 2,4,5-trisubstituted-2-imidazolines and thoroughly investigates the reaction mechanism. The reaction was optimised by performing the synthesis at different temperatures, using a range of ammonia sources and eleven different green solvents, namely 2-MeTHF, sulfolane, DMSO, MTBE, CPME, 1-butanol, butyl acetate, dimethyl carbonate, water, diphenyl ether and Cyrene. The influence of p-substituent was studied by varying the substituent of aldehydes. The product was obtained using aldehydes with electron withdrawing groups with yields up to 87%. The effect of p-substituent was further investigated by investigating the kinetics and comparing the reaction rate of each chemical transformation. Quantum mechanical calculations were performed and compared to the experimental results to thoroughly study the reaction mechanism. The limitation of the 2-imidazoline synthesis was further studied by performing the reaction with o-, m-substituted as well as heterocyclic and non-aromatic aldehydes. While in almost every case 2-imidazoline product was isolated, with a non-aromatic aldehyde a trisubstituted imidazole product was obtained through intramolecular double bond migration, surprisingly. While a green reaction was proposed in this research work complying with 5 out of 12 green principles, the purification and isolation of the desired product usually requires solvent- and energy intensive separation methods. In order to mitigate the unsustainable nature of these separation techniques, organic solvent nanofiltration was proposed as a green alternative for the purification of products. For this objective, four commercial membranes were screened for the separation of aldehyde and a 2-imidazoline product. Then a membrane with the highest performance was selected and a diafiltration process was proposed for the purification of the crude product.

Date of Award	3 Jan 2018
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Arthur Garforth (Supervisor) & Gyorgy Szekely (Supervisor)