Synthesis Of 4-(2-aminophenyl)-2-diazobutyrate And Its Conversion In Organic Synthesis

Tetrahydroquinoline(THQ)is widely found in natural products as a nitrogen-containing heterocyclic compound.It is widely used in pesticides,pharmaceuticals and materials because of its good pharmacological and biological activities.Most of the reported methods for the construction of tetrahydroquinoline derivatives have been performed by metal/nonmetal-catalyzed intramolecular cyclization reactions of amides/imines;however,the above methods involve structurally more complex raw materials,thus requiring additional reaction and purification steps,which reduce the reaction economy and greatly limit the further research and application of tetrahydroquinoline derivatives.Therefore,the development of new synthetic methods for tetrahydroquinolines is of great research value.In this thesis,two new methods for the construction of tetrahydroquinoline derivatives were developed using 4-(2-aminophenyl)-2-diazo-butyrate as the raw material.The details of the study are as follows.In the first part,a new method for the synthesis of 4-(2-aminophenyl)-2-diazobutyrate was investigated.The reported synthesis method of methyl 4-(2-aminophenyl)-2-diazobutyrate was optimized to develop a simple and efficient synthesis method.The method successfully prepared more than ten 4-(2-aminophenyl)-2-diazobutyrate derivatives in good to excellent yields by using cheap and readily available o-aminophenethyl alcohol as the raw material,through addition reaction,acylation reaction,coupling reaction,diazotization reaction,and amine deprotection reaction,and expanded the applicable range of substrates.Meanwhile,the method can be scaled up to gram-scale reactions,providing the possibility of further derivatization.The method is optimized and complementary to the original synthesis method,which has the following advantages: 1)simple and easy to obtain raw materials;2)mild reaction conditions;3)short reaction time;4)no transition metal catalysis.In the second part,a Rh/Pd bimetallic synergistic catalytic tandem reaction of aziridine with allylpalladium was developed to construct 2,2-disubstituted tetrahydroquinoline derivatives.The reaction constructs the aza-elide intermediate via a rhodium-catalyzed intramolecular N-H bond insertion reaction of methyl 4-(2-aminophenyl)-2-diazobutyrate,followed by a palladium-catalyzed reaction with an allylated reagent to obtain an allylpalladium intermediate,which in turn undergoes nucleophilic addition with the aza-elide intermediate to produce 2,2-disubstituted tetrahydroquinoline derivatives.The reaction has the following advantages: 1)mild reaction conditions;2)rapid reaction;3)no contamination;4)high chemoselectivity;5)wide range of substrates.On this basis,the exaggeration reaction and product derivatization were carried out to illustrate the potential applications of the products,and the reaction mechanism was proposed.