Synthesis Of N - Heterocyclic Amide Derivatives By Direct Amidation Of Copper - Supported Saturated Heterocyclic α - C - H Bond And Its Bioactivity

Amide moiety is one of the most important class of functional groups in organic chemistry. It has attracted extensive attention because of its widespread occurrence in natural products, proteins and the synthetic pharmaceuticals, materials, and other functional molecules. How to create the amide bonds more easily and introduce the amide moieties into other constructions to change the structures and properties are two fields of the research focus. N-acyl-N, O(S)-aminals which contained amide bonds extensively exist in natural products and synthetic pharmaceuticals. These molecules play important roles in anti-cancer drugs, fungicides and herbicides. This thesis mainly studied two aspects. One is the synthesis and the antifungal, antibacterial activities of N-acyl-N, O(S)-aminals, and the other is how to create amide bonds from aldehydes and aromatic amines.1. A facile and efficient strategy to synthesize N-acyl-N, O(S)-aminals has been developed. The target compounds were obtained by CDC reaction(CrossDehydrogenative-Coupling Reaction) directly from amides and ethers in the presence of Cu(OTf)2 and TBPB in mild conditions, the yield could reach to 86%. The substrates did not need to prefunctionalize in this procedure and the step-economy was high. After the investigation of the adaptability of amides and ethers, we found that thioethers could also convert to the corresponding products with amides smoothly. To the best of our knowledge, this was the first time to synthesize N-acyl-N, S-aminals directly from amides and thioethers. The bioassay of these compounds indicated that only compound 3i shows inhibitory activity against X. cirri about 47.6±1.5% at 100 μg/mL and 3ac shows inhibitory activity against C. mandshurica about 46.1±1.5% at 50 μg/mL. Other compounds do not show obvious inhibitory activities to these fungi and bacteria.2. A facile strategy to prepare amide bonds has been developed. A series of amide compounds, including heterocyclic amide compounds, were obtained with moderate to good yields ranging from 33-88% by using copper iodide(CuI) to catalyze the oxidative amidation between aldehydes and amines under solvent-free conditions at room temperature in air. The tentative exploration of the mechanism indicated that the intermediate in this reaction was not imines or carboxylic acids but rather hemiaminals.