One Pot Three-Component Reaction For Preparation Of Dihydroquinolines With Two Different Ketones And Aromatic Amines

Domino reaction has become one of the popular methods pursued by modern organic chemists due to its simple operation,complex and variable product structure and high efficiency.Nitrogen-containing heterocyclic compounds are widely found in nature due to their unique inter-atomic arrangement and bonding type,and currently the nitrogen-containing heterocyclic skeleton accounts for 60% of the heterocyclic compound.Therefore,nitrogen-containing heterocyclic compounds have always been a research hotspot for chemists.1,2-dihydroquinoline has excellent anti-oxidation,anti-inflammatory,anti-bacterial and anti-cancer activities due to its unique structure and biological activity,and is widely used in food additives,pharmaceuticals,biochemistry and materials.Based on These applications,methods of refining and developing such compounds are very important.Regarding the synthesis of dihydroquinoline,a lot of work has been done by the predecessors.At present,the more common methods generally have the following categories:(1)traditional Skraup reaction and Skraup-Doebner-Von-Miller reaction(2)intramolecular Wacker-type reaction(3)transition metal catalyzed hydroamination reaction of aniline and alkyne(4)Other types of reactions.However,most of the above methods have the characteristics of cumbersome steps,harsh experimental conditions or environmentally unfriendly characteristics,and the type of reaction products is single,which cannot meet the screening requirements of medicinal chemistry.Therefore,it is urgent to study the synthesis of 1,2-dihydroquinoline which is efficient,fast and multi-substituted.Based on the synthesis of early 1,2-dihydroquinoline,ketone ester,ketone and aromatic amine were used as substrates,and a novel domino series Skraup reaction was carried out under the catalytic conditions of Lewis acid Sc(OTf)3.A variety of 1,2-dihydroquinolines with multiple substituents were constructed,which provided a good active precursor for subsequent structural modification.Based on the effect of substituents on product selectivity in the formation of ethyl benzoylformate derivatives by the Friedel acylation reaction,we have improved the synthesis of early ketoesters,which is simple,fast,and low cost.Based on the advantages of high yield,low pollution and good selectivity,we have constructed 8 kinds of aromatic keto esters,and selected the best conditions.Based on this,we will introduce keto esters,ketones and aromatic amines.In the "pot method" reaction,25 substituents of various 1,2-dihydroquinoline compounds were synthesized.The mechanism was explored and a reasonable reaction mechanism was proposed.