Study On The Synthesis Of Nitrogen-containing Heterocyclic Compounds Via Intermolecular Annulation

Nitrogen-containing heterocyclic compounds are common organic compounds that exist widely in a variety of natural products and synthetic molecules.Nitrogen-containing heterocyclic compounds have been widely used in biology,medicine,materials and other fields becase of their special structures and unique biological activitis.Intermolecular annulation has been the most straightforward and effective tool in the construction of the ring skeleton because of high step economy and atomic economy,avoiding the prefunctional group of the reaction substrates and reducing the number of steps of chemical synthesis.In recent decades,a large number of researchers have applied intermolecular annulation reactions in the synthesis of nitrogenous heterocycles and achieved some achievements.Nevertheless,it is still a hot research field for chemists to develop more simple,efficient and environmentally friendly intermolecular annulation strategies for the synthesis of nitrogenous heterocycles.Aldehydes,ketones and amines,as readily available raw materials,have been frequently found in synthetic chemistry.In this thesis,we explored new intermolecular annulation reactions involving aldehydes,ketones and amines as raw materials,and developed new strategies to synthesize nitrogen-containing heterocyclic compounds.The main works included the follows:1.A [4+1+1] annulation of o-aminobenzyl alcohols,aldehydes and sulfoxides to quinoline compounds in the promotion of KOH was studied.When dimethyl sulfoxide was used as a substrate,dimethyl sulfoxide provided a carbon atom to the C2 position of the quinoline ring,and aldehydes provided a carbon atom to the C3 position of the quinoline ring.When α-substituted sulfoxides were used as substrates,the positions between aldehydes and sulfoxides in the product quinolines were interchanged.This reaction can be used to synthesize regioselectively 3-,4-,3,4-,2,3-,2,3,4-substituted quinolines by the choice of different o-aminobenzyl alcohols,aldehydes and sulfoxides as substrates.Finally,a plausible mechanistic pathway for this [4+1+1]annulation reaction was proposed based on a series of control experiments and relevant literature,2.A [3+1+1+1] annulation of arylamines,arylaldehydes,and dimethyl sulfoxide for the synthesis of 3-arylquinolines in the presence of potassium tert-butoxide and potassium persulfate was disclosed.In this reaction,dimethyl sulfoxide was not only used as a solvent,but also as a nonadjacent dual-methine(=CH-)synthon.This annulation formed three C-C and one C-N bonds.Under optimal conditions,a series of aromatic aldehydes and anilines can be converted into the corresponding3-arylquinolines.The protocol was successfully applied in gram-scale reaction.Finally,a plausible mechanistic pathway for this [3+1+1+1] annulation reaction was proposed based on a series of control experiments and relevant literature.3.A [2+1+1+1] annulation of methyl ketones,amines,and ammoniums for the synthesis of 1,2,5-trisubstituted imidazoles in the promotion of iodine and potassium persulfate was developed.In this annulation,two molecules of methyl ketones provided three carbon atoms,and amines and ammoniums contributed one nitrogen atom to imidazoles framework,respectively.This annulation reaction formed four C-N bonds.Various methyl ketones,aromatic amines,and aliphatic amines were suitable for this annulation.The protocol was successfully applied in gram-scale reaction.Finally,a possible mechanistic pathway for this [2+1+1+1] annulation reaction was proposed based on a series of control experiments and relevant literature.4.A [2+2+1] annulation of amines and arylacetaldehydes to 1,3,4-trisubstituted maleimide with dimethyl sulfoxide as solvent in the presence of potassium persulfate was studied.In this reaction,arylacetaldehyde served as dual carbon donor,amine served as nitrogen source,and dimethyl sulfoxide served not only as solvent but also as carbonyl oxygen source.Under optimal conditions,a series of arylacetaldehydes and amines can be successfully converted into the corresponding maleimide compounds,and N-aryl and N-alkyl substituted maleimides were synthesized.Finally,a plausible mechanism for this [2+2+1] annulation reaction was proposed by designing a series of control experiments and reviewing relevant literature.