Study On Cascade Synthesis Of Nitrogen-Containing Heterocycles Based On PDF Conversion

As a very important class of organic compounds,nitrogen-containing heterocycles are the basic structural unit of many marketed drugs and natural products,and widely existed in chemical drugs,agro-chemicals,fine chemicals,organic functional materials,and many other fields.Developing simple and high-efficient methods or strategy for construction of nitrogen-containing heterocycles is always the research hotspots in organic synthetic field.Among many reported methods for synthesis of nitrogen-containing heterocycles,cascade reaction is one of the most highly efficient and green protocols because of its atomo economy,simple work-up procedure.In recent years,cascase reactions have been become one of the most intriguing interests in organic synthesis.Our group mainly focuses on the PDF conversion of o-aminonitriles with various carbonyl compounds.However,we have never studied the PDF conversion based on other reactants except o-aminonitriles.In order to expand the application of PDF conversion,we designed and studied the cascase reaction for synthesis of 1,3-benzoxazin-4-ones and quinazolin-4?3H?-ones from two different substances via changing the functional groups.The specific contents are as follows:1.Study on the PDF conversion of 2-hydroxybenzonitriles with various ketones2-Hydroxybenzonitriles were used as analogues of o-aminonitriles,we studied the PDF conversion of 2-hydroxybenzonitriles and various carbonyl compounds,and found Lewis acid ZnCl₂ can promote the reaction affording 2,3-dihydro-4H-1,3-benzoxazin-4-ones via PDF conversion pathway.15 products of PDF conversion were obtained in the thesis,and the structures of all products were characterized by IR,ESI and NMR spectra.In addition,the structure of product 2.3a was further confirmed by X-ray crystallography.2.Cascade reaction for synthesis of quinazolin-4?3H?-ones via C-N coupling and PDF conversionIn dissertation,we studied the copper-catalyzed cascade protocol for synthesis of quinazolin-4?3H?-one derivatives by using commercially available 2-halobenzonitriles and amides as starting materials,inexpensive CuI as the catalyst and cheap inorganic base as a promoter.2-Halobenzonitriles bearing electron donating or electron withdraw groups reacted well with aromatic or aliphatic formamide.The key intermediate N-?2-cyanoaryl?amide which is the product from the Ullmann-type coupling of2-halobenzonitrile with amide was obtained,and further converted to give the aimed product under the same conditions.Besides,we also did some isotopic labelling studies and the possible mechanisem was proposed.What's more,another copper-catalyzed cascade method for synthesis of quinazolin-4?3H?-ones was established via Chan-Lam coupling and PDF conversion,which using 2-cyanoboric acid and amide compounds as starting material,and the corresponding products were obtained in high to excellent yields.3.Study on the domino reation of o-aminonitriles with olefinsIn this part,the selective oxidation reaction of olefins was involved to the PDF conversion.We designed the tandem reaction of styrene and o-aminonitriles.Firstly,a simple,efficient Wacker catalystic system for selective oxidation of styrenes was established which using Palladium?II?complexes as catalyst,O₂ as sole oxidant.And then we studied the Wacker/PDF cascade process,sevral desired products were get with moderate yield through step-by-step feeding.However,the reaction conditions and substrate scope will be further studies.