Synthesis, and characterization of new derivatives of N-Substituted Phenyl Benzimidazolo-1,3,5,-Triazine

Abstract

The aim of this study is the synthesis of new benzimidazolo-1,3,5- triazine derivativesand their characterization by means of several techniques such as: FTIR, 1H-NMR, 13C-NMRand Mass spectroscopies. The effect of ultrasound irradiation on the synthesis has beeninvestigated. Finally, the biological activities of the obtained compounds have been evaluatedand correlated with the structural properties of benzimidazole-1,3,5- triazine derivatives.In this work, new benzimidazole-1,3,5- triazine derivatives were synthesized via thereaction between imidate and phenylisocyanate or substituted phenylisothiocyanate in THFas solvent. Basically, two different methods were used: (i) ultrasound irradiation (60 kHz) at45°Cand (ii) at room temperature. The different substituted phenyl-benzimidazolo-1,3,5-triazine-4-one and substituted phenyl-benzimidazolo-1,3,5-triazine-4-thione were successfullyobtained.Herein, ultrasound irradiation method was found to minimize the reaction time andenhance the products yields. The obtained heterocycles were screened for theirantihistamine, antidiabetic and antimicrobial activities. Most derivatives exhibited interestingbiological properties as anti-diabetic, antihistamine, and antimicrobial. The compounds 3-(4-fluorophenyl)-2-ethyl[1,2-a] benzimidazolo-1,3,5-triazine-4-thione, and 3-(4-chlorophenyl)-2-ethyl[1,2-a]-benzimidazolo-1,3,5-triazine-4-thione, showed a significant α-amylase inhibitionwith IC50=59.9,52.1, respectively. On the other hand, compounds 3-(4-chlorophenyl)-2-ethyl[1,2-a]-benzimidazolo-1,3,5-triazine-4-thione, and 3-(4-chlorophenyl)-2-methyl [1,2-a]benzimidazolo-1,3,5-triazine-4-thione, showed a high activity as anti-histamine, and antimicrobial than the others. Also, compounds 3-phenyl-2-ethyl [1,2-a]-benzimidazolo-1,3,5-triazine-4-thione showed antimicrobial activity.This work is divided in to three main chapters: The first chapter is committed tointroduce the importance of heterocyclic compounds and investigate the most importantprevious studies, including the preparation of imidate, and triazine, and some biologicalactivities of known triazines.In second chapter, the experimental methods have been extended for the synthesis ofN-(2-benzimidazolyl) imidate, benzimidazolo-1,3,5-triazine, and for the presentation ofbiological activities techniques.The third chapter is dedicated for explaining the mechanisms of the obtained products,namely the N-benzimidazolyl imidate and the N- benzimidazole-1,3,5-triazine derivatives. Theobtained products were deeply characterized by means of FTIR, (1H,13C) NMR and massspectroscopies and by Thermogravimetric analysis (TGA). Finally, the biological activities ofbenzimidazole-1,3,5-triazine derivatives have been discussed.