Synthesis of potential anticonvulsants based on chloral hydrate and carbamazepine: their spectral characteristics and in silico ADME profiling

Abstract

This paper reports the synthesis of a new potential anticonvulsant, N-(2,2,2-trichloro-1-hydroxyethyl)-5H-dibenzo[b,f]azepine-5-carboxamide. Its synthesis is based on condensing the anticonvulsant drug carbamazepine with chloral hydrate used in medical practice. The reaction was carried out in a melt or by boiling in dry benzene with the removal of the resulting water from the reaction medium. The product was obtained with yields of 88 and 79%, respectively. Replacing the hydroxyl group in the resulting condensation product with an amino group led to the formation of N-(1-amino-2,2,2-trichloroethyl)-5H-dibenzo[b,f]azepine-5-carboxamide. This synthesis was carried out in two stages. Initially, the hydroxy derivative was chlorinated with thionyl chloride. Then, by treating the resulting chlorine derivative with an aqueous solution of ammonia (25%) in MTBE medium, the target product was obtained. The structure of the obtained compounds was proven by 1H NMR and IR spectroscopy data. The SwissADME online platform showed that the synthesized compounds should have high bioavailability as well as moderate solubility in water and be able to penetrate the blood-brain barrier.