Synthesis Of 1,1'-biphenyl-2,2'-diamine Compounds By Cross Dehydrogenative Coupling And Synthesis Of Antidepressant Drug Vilazodone

This paper consists two parts.Part one was the synthesis of 2,2'-biphenyldiamine compounds through cross dehydrogenative coupling.Part two focused on the synthesis of antidepressant drug vilazodone.Part one is consisted of three chapters.The first chapter reviewed the application and the traditional synthetic method of 2,2'-dinitrobiphenyl compounds.The second chapter reviewed the application of cross dehydrogenative coupling in the synthesis of biaryl compounds.We developed a green and efficient method employing carbamate functionality as the directing group to synthesize 1,1'-biphenyl-2,2'-diyldicarbamate derivatives via dehydrogenative C-H/C-H arylation under ball-milling conditions,which can be easily hydrolyzed to 2,2'-biphenyldiamine.A series of experiments were carried out under different conditions and various of substituted methyl phenylcarbamate were used to test the generality of the reaction.Seventeen 1,1'-biphenyl-2,2'-diyldicarbamate derivatives were synthesized with 35-88% yields.Eight 1,1'-biphenyl-2,2'-diamine compounds were synthesized with 75-95% yields.Comparing to traditional methods,this method has the advantages of short reaction time,moderate reaction temperture,and don't require pre-functionlization of substrates which lead to high atomic economy.Part two reviewed the synthesis of antidepressant drug Vilazodone.We designed a route for the synthesis of 5-(piperazin-1-yl)benzofuran-2-carboxamide which employed 5-bromobenzofuran-2-carboxamide and piperazine as substrates by Ullmann coupling reaction with 49.3 % yields.And then,we chose 5-(piperazin-1-yl)benzofuran-2-carboxamide and 3-(4-chlorobutyl)-1H-indole-5-carbonitrile as substrates to synthesis vilazodone.We also discussed the influence factors,such as catalysts,ligand,base,solvents and temperature.This method provided the desired vilazodone with 75% yield.And it is a short reaction route that has the potential for industrial production of vilazodone.