The Synthesis And Molecular Structure Characterization Of The Derivatives Of Imidazole Or Thiazole Possessing Potential Bioactivity

Nitrogen-containing heterocyclic compounds and their derivatives have found greater and greater application as intermediates of medicine, pesticide, dye and other fine chemical engineering's products. The introduction of nitrogen-containing heterocyclic compounds and their derivatives into some organic compounds generally brings about increased bioactivity of the organic compounds. Because of their high selectivity and bioactivity, nitrogen-containing benzoheterocyclic compounds play an important role in the research and exploitation of drugs and have become the focus of research in pesticides and medicines. However, according to our knowledge, relatively less research has been carried out on nitrogen-containing benzoheterocyclic compounds, such as 3,4-dihydro-2(1H)quinoxalinone, 1,2,3,4-tetrahydroquinoxaline, 2,3-dihydro-l,4-benzoxazine, 2,3-dihidrobenzoxazole and 2,3-dihydro-l,4-benzo-thiazine. In fact, they play an important role in the medicine. Probably they are pharmacological active centers and possess bioactivity.The imidazoles and the thiazoles, existing in nature, are of great significance in the research and exploitation of drugs. There are imidazole or thiazole rings in the structures of many clinic medicines. At the same time, many newly developed compounds containing imidazole ring or thiazole ring also have bioactivity. Therefore, it can be concluded that both imidazole ring and thiazole ring have bioactivity.The theories about drug design, such as Quantitative Structure-Activity Relationship (QSAR), have some effects on forecasting the bioactivity of compounds and helping us to understand pharmic mechanism, and can direct us to design target molecule (TM). Combined with the idea of Free-Wilson model, two kinds of molecules owning potential bioactivity were designed, and their structures are shown as follows:Five types of nitrogen-containing benzoheterocyclic compounds were designed and synthesized in order to obtain target molecules. Based on the previous researches in our laboratory, synthetic methods of these compounds were optimized by comparing different synthetic methods. Now these compounds can be prepared from inexpensive and available materials. The reactions of these nitrogen-containing benzoheterocyclic compounds with chloracetyl chloride or chloracetyl bromide at room temperature in DMAC can produce the corresponding N-chloracetyl or N-bromoacetyl-substiuted nitrogen-containing benzoheterocyclic compounds.In the presence of K2CO3 and TBAI in CH3CN, TM1-TM5 were synthesized through nucleophilic substitution reaction between imidazole and N-bromoacetyl or N,N'-dibromoacetyl substituted nitrogen-containing benzoheterocyclic compounds.By using Na2CO3 as a base in acetone, four types of N-chloroacetyl or N,N'-dichloroacetyl substituted nitrogen-containing benzoheterocycles were introduced into thiazole through the formation of thio-ether. TM6-TM9 were obtained in good yields after column chromatography or recrystallization.In conclusion, nine novel compounds with potential bioactivity were synthesized through different approaches. MS, 1H NMR, 13C NMR, DEPT, IR and elementary analysis have identified the structures of them.