Synthesis Of Indene Derivatives Through Intramolecular Prins Reaction

Indene is an important class of polycyclic aromatic hydrocarbons,and it is widely present in many biologically significant natural products and drug molecules.Many indene derivatives have very important pharmacological and biological activities,such as anti-allergic,anti-tumor,and anti-microbial activities.In addition,they have many applications in materials science and as metal complex in catalytic chemistry.Due to the wide application value of indene derivatives,there have been many reports on the synthesis of these compounds at home and abroad.However,many reported synthetic processes have some drawbacks which limit their applications in industry.Therefore,the development of new and efficient methods to synthesize indene derivatives has become a hotspot in the organic field.The methods to synthesize indene derivatives is mainly divided into intramolecular cyclization and intermolecular cycloaddition reactions.The Prins or carbonyl-ene reaction is a condensation reaction between a carbonyl group and an unsaturated C-C bond to generate a homoallyl or allyl alcohol compound under the catalysis of Lewis or Br(?)nsted acid.The reaction is mainly divided into two modes: internal cyclization reaction and external cyclization reaction.This reaction provides a facile access for the construction of carbon-carbon bonds and cyclic compounds,and has been widely applied in both laboratory and industry.In this thesis,a new method for the synthesis of indene derivatives has been developed through an intramolecular Prins internal cyclization reaction.The reaction employs ortho-alkenyl benzaldehydes or ketones as the starting materials,it reacts with trimethyl orthoformate or acetic anhydride to give an oxonium ion intermediate,which then undergo an intramolecular Prins cyclization to furnish the corresponding indene ether or indene ester derivatives.The optimal reaction conditions include: Tf OH as the catalyst,1,2-dichloro ethane as the solvent,reaction temperature 40-60℃.Under this condition,the limitation and scops of this reaction was studied,31 indene ether derivatives and 11 indene ester derivatives were obtained in good yields.Additionally,this method also can be used for the synthesis of alkene substituted indene derivatives.In order to understanding the reaction mechanism,several control experiments were conducted.The results preliminarily proved that the oxonium ion may be the reaction intermediate.To date,there are only a handful methods have been reported for the synthesis of indene ether and indene ester derivatives.This study provides an efficient protocol for the synthesis of these compounds.Our method has some advantages including mild reaction conditions,easy preparation of raw materials,simple operation,no use of metal catalysts,high atom-economy and so on.Therefore,it has a good application prospect.