Methodology For The Direct Amidation Of Metal-catalyzed Saturated Heterocyclic ?-CH Bonds To Synthesize Heterocyclic Amide Derivatives

The amide bond,as one of the functional groups that construct the important skeleton of the compound,is indispensable in organic chemistry and biochemistry.It is not only prevalent in the chemical synthesis of drugs and natural product extract molecules,but also widespread in the protein,peptides,materials and other functional molecules,which has attracted the eyes of many chemists.How to introduce the amide structure into other molecules more efficiently and simply to change its structure and properties is one of the research focus.In addition,the heterocyclic structure as the important active skeleton in drug molecules,is widely used in various types of medicines and pesticides creation.Among them,pyrazole ring and oxadiazole ring derivatives have become one of the hot spots of research scholars because of its extensive biological activity.This thesis mainly studied two aspects.One is the synthesis and the antibacterial activities of compounds containing N-acyl-N,N-acetal moieties,and the other is antimicrobial evaluation of pyridinium-tailored 5-trifluoromethylpyrazoles containing 1,3,4-oxadiazole scaffolds.1.A facile and efficient strategy to synthesize compounds containing N-acyl-N,N-acetal moieties has been developed.The target compounds were obtained by CDC reaction directly from the amide and saturated nitrogen heterocyclic compounds in the presence of copper catalyst(Cu(OTf)2)and oxidant(TBHP)in mild condition,which achieves the direct functionalization of the inactive C-H bond.This method does not require the substrate to be prefunctionalized,whose the step-economy was high and the reaction conditions are mild.After the investigation of the adaptability of amides and saturated nitrogen heterocyclic compounds,We found that other amides can also convert to the corresponding product smoothly with N-phenylmorpholine.To the best of our knowledge,this compounds were synthesized for the first time by N-phenylmorpholine and amides.The bioassay of the synthesized compounds showed that all the tested 12 compounds had certain inhibitory activity against Xanthomonas Oryzae,Xanthomonas axonopodis pv.Citri and Ralstonia solanacearum.The inhibitory rates of compounds A-4 and A-7 were 49.6±0.3% and 58.9±0.6% at 100 ?g/mL against Xanthomonas Oryzae.the inhibition rates of the compounds A-10,A-4 and A-7 were 50.9±3.9%,62.7±0.9% and 58.9±0.4% at 100 ?g/mL against Xanthomonas axonopodis pv.Citri.The inhibitory rate of the compounds A-5 and A-4 were 51.3±2.6% and 55.4±5.4% at 100 ?g/mL against Ralstonia solanacearum.2.Pyridinium-tailored 5-trifluoromethylpyrazoles containing 1,3,4-oxadiazole scaffolds were synthesized and characterized by 1HNMR,13 CNMR,19F NMR and MS.The antibacterial activities of all the compounds were tested by the nephelometry in vitro.After testing EC50 values against Xanthomonas Oryzae,Ralstonia solanacearum and Xanthomonas axonopodis pv.Citri about 15 compounds,we found the target compounds have positive inhibitory activity against three plant bacterias.The results showed that the lowest EC50 values of the tested compounds were 0.467 ?g/mL,1.04 ?g/mL and 0.600 ?g/mL,respectively,for the pathogens of Xoo,R.solanacearum and Xac.The antifungal activities were screened and evaluated against six pathogenic fungi,namely,B.cinerea,F.oxysporum,C.mandshurica,F.Grammingarum,P.infestans,and T.cucumeris,by the mycelial growth rate method.The results indicated that all target compounds are positive inhibitory activity against B.cinerea at 50 ?g/mL,an I-10,I-12,II-12,and IV-12 showed the strongest growth suppression radical Rhizoctonia solani with EC50 values ranging from 10.2 to 24.0 ?g/mL.Through the structure-activity relationship,it was found that with the increase of the length of the alkyl chain,the inhibitory activity of the three species of plant pathogenic bacteria and six plant path fungi increased for the thioether series and the Oxygen ether series compounds with different alkyl chain lengths.It indicated the alkyl chain length is beneficial to improve the biological activity of the target compound.