Copper-Catalyzed Water-Mediated C-N Cross-Coupling Reactions

Benzimidazoles are a class of privileged core structures found in a broad spectrum of usage in the field of pharmacy, industry, catalyzing chemistry, functional materials and so on owing to their good bioactivity, corrosion stability, catalytic activity as well as some other properties. One research purpose for numerous chemists, therefore, is devoting themselves to the development of methods for the efficient preparation of benzimidazoles.It is an efficient way to synthesize benzimidazoles by transition-metal-catalyzed C-N cross-coupling reactions. Most traditional reactions on C-N bond formation are proceeding in organic solvents, which are commonly poisonous to human body and even pollutional to environment. Because water is non-poisonous, environment benign, cheap and available, it is favoured by lots of chemists as an ideal solvent, what's more, water mediated organic reactions become one of the hot topics. For the reasons listed above, this thesis aims at developing an efficient synthesis of benzimidazoles via cheap and low toxic transition metal catalyzed Ullmann N-arylation using water as the reaction media.Utilizing 5 mol% cheap, low toxic and available Cu2O as the catalyst,10 mol% N,N' dimethylethane-1,2-diamine as the ligand, K2CO3 as the base and water as the solvent, N-(2-halogen substituted aryl) amidine could undergo intramolecular Ullmann N-arylation at 100℃to produce benzimidazoles. Our research shows that the nature of the ortho substituted halogen on the aniline moiety is very important to the reaction outcome. The reactivity of different ortho substituted halogen on the aniline moiety amidine follows the sequence of I Br> Cl. (Ortho-iodoaryl) amidines or (ortho-bromoaryl) amidines can smoothly be converted to the desired products in high to excellent yields. However, the use of aryl chlorides to effect such transformations afford inferior results than their iodo or bromo analogues. For aryl iodides or bromides, a variety of substituents on the benzonitrile moiety, such as Me, OMe, Cl, Br or CN can be used. Regarding the aniline moiety, several functional groups including halogens and electron-donating (Me and OMe) or electron-withdrawing (NO2) substituents are tolerated well.This thesis has developed a practical, inexpensive, available and efficient method to synthesize benzimidazoles. This protocol is not only a valuable addition to the tool box of the synthesis of benzimidazoles, but also enriches the contents of Ullmann C-N cross-coupling reactions and water mediated organic reactions.