Amidines- Or Ketenimines-based Cycloadditions For Synthesis Of Nitrogen-containing Compounds

As nitrogen-containing organic compounds,amidines are often used as synthetic precursors of heterocyclic compounds.In the previous studies,amidines can undergo cycloadditions with different types of compounds to produce nitrogenous compounds,such as triazines,imidazoles,pyridines,quinolines,and pyrimidines,etc,which are widely used in medicinal chemistry.Ketenimines with C=C bond and C=N bond in the structure,have the chemical properties of the allenes and ketenes.On the one hand,the N atom on the accumulated double bond of ketenimines destroys the symmetry of its own structure and make it have more abundant reaction sites than the olefin.On the other hand,ketenimines are more reactive in some chemical properties due to the high polarity of the C=N double bond.Therefore,the cycloadditions involving amidines and ketenimines have attracted great attention from chemical researchers.In this thesis,1,2-dihydro-1,3,5-triazines derivatives were first prepared by cycloaddition of amidines with paraformaldehyde using Cu?OAc?₂ as a catalyst.The experiments were carried out using N-phenylbenzylhydrazine and paraformaldehyde as starting materials,and a systematic investigation on the effects of reaction conditions was discussed.The results showed that the optimal reaction conditions were 0.2 mmol of paraformaldehyde and 2.2 equiv of N-phenylbenzamidine as raw materials,1.0 mL of EtOAc as a solvent,25 mol%Cu?OAc?₂ as a catalyst,80 ^oC as reaction temperature for 16 hours,and the yield of the desired product can be up to 88%.Under the optimal reaction conditions.The examination of the substrate scope indicated that the reaction could be applied to the majority of the investigated materials and obtained high yields.Then,the reaction mechanism was proposed.Secondly,the preparation of 1,2-dihydro-1,3,5-triazines derivatives by cycloaddition of amidines with aldehyde were investigated.The reaction of N-phenylbenzamidine with benzaldehyde was used as a standard reaction,and the effects of catalysts,catalyst loading,solvents,solvent dosage,reaction temperature and the ratio of materials on the reaction were studied.The optimal reaction conditions were as follows:0.2 mmol of benzaldehyde and 2.1 equiv of N-phenylbenzylhydrazine as raw materials,1.5 mL of EtOAc as a solvent,10mol%of ZnI₂ as a catalyst,at 80 ^oC.The results indicated that the product yield can reach up to 76%under optimal reaction conditions.The study on substrate scope showed that most substrates can obtain moderate to good yields.The reaction mechanism was also proposed.Finally,the cycloaddition of ketenimines with aziridines was studied.The optimal reaction conditions were determined by conditional optimization:0.1mmol of diethyl 3-?o-tolyl?-1-tosylaziridine-2,2-dicarboxylate and 2.3 equiv of N-?2,2-diphenylvinylidene?aniline as raw materials,1.0 mL of CHCl₃ as a solvent,0.8 equiv of SnCl₄ as a promoter,and the reaction was carried out at 30^oC for 2 h.The yield of the desired product can reach up to 93%.Studies on substrate scope for aziridines and ketenimines under optimal conditions,indicated that most substrates were able to be converted to the produce in the condition in moderate to good yields.Then,the reaction mechanism was proposed.By the cycloaddition of amidines with paraformaldehyde/aldehydes compounds and the cycloaddition of ketenimines with aziridines,triazines and imidazolidine derivatives were successfully obtained.The methodology have the following advantages:?1?cheaper catalyst,?2?mild reaction conditions,?3?simple reaction systems.