The Synthesis Of Novel Benzo[4,5]Imidazolo[1,2-b]Pyrazoles Using New Thioamides As Synthon

Benzimidazole compounds as the first internal suction fungicides have good selectivities, relatively high mammals security and wide antibacterial spectrum. They can make a great contribution to sustainable high yield for the crop by controlling the diseases caused by fungi. Pyrazoles occupy a certain proportion in the existing pesticides and these compounds generally have high bioactivities. So the research on the synthesis of pyrazole compounds is very important.β-ketothioamides (KTAs) as a a-oxoketene N, S-acetals, have been shown to exhibit intriguing multinucleophilic reactivities and proven to be important building blocks in the construction of heterocyclic systems.Ullmann reactions are widely applied for the formation of C-N, C-O, C-S, C-X, C-C bonds. The most usual and efficient ligands are divided into N, N-, N, O-, O, O-types. The heterocyclic ketene amines (HKAs) with N, O-and O, O-the two structural characteristics is widely used as a polyfunctional synthon for the construction of heterocyclic compounds, but as an organic ligand used for the formation of the catalyst system with copper salts has not been reported so far. The ligand forms a metal complex with copper salts to catalyze the reactions.The first chapter introduced the wide use of isothiocyanates and thioamides in organic synthesis and the development of the copper catalytic reactions and ligands.The second chapter proposed a new method for synthesis of the β-ketothioamide by using KOAm-t/toluene instead of the conventional method NaH/1,4-dioxane as the catalyst to give N-(2-bromophenyl)-3-oxo-3-arylthiopropanamide, and the reaction yields are up to93%. A series of pyrazole derivatives (4a-4r) were obtained using the β-ketothioamide and hydrazine hydrate as raw materials in refluxed ethanol for1h. The present method shows fascinating properties such as concise short reaction times, easy purification and avoids the use of transition metals.In the third chapter, we have demonstrated for the first time that medicinally useful benzo[4,5]imidazo[1,2-b] pyrazole derivatives (5a-5r) can be easily prepared by the coupling reactions of pyrazole derivatives (4a-4r) using a combination of CuCl and a HKAs-type ligand in good yields within10min. Compared with the reaction system CuI/NaH/L-proline reported by Junjappa, we use the cheaper CuCl as a catalyst and K2CO3as the base instead of the greatly dangerous NaH. Also, when L4was used as ligand the reaction yields are up to higher than90%, and the reaction time is shortened, as well as it wided the limit for the reaction substrates.The structures of all the target compounds were confirmed by IR,1H NMR,13C NMR, and HRMS, and the plausible mechanism was also presented. The unambiguous molecular structure of4p was determined by X-ray diffraction analysis.