Study On The Synthesis Of Benzoheterocyclic Compounds Catalyzed By Br?nsted Acid Regulating Titanocene Dichloride

In this paper,we designed a series of reactions catalyzed by dichlorotitanocene as core catalyst and organic Bronsted acid as adjusted ligand through a binary acid cooperative catalytic strategy of Lewis acid-Bronsted acid aiming to synthesize 1,2-disubstituted benzimidazole,1,5-benzodiazepine and benzothiazoles,combined with the previous research about metallocene catalysis.We develop three highly efficient methods to synthesize heterocyclic compounds catalyzed by Cp2TiCl2 cooperated with Bronsted acid.in-situ NMR,ESI-MS and single crystal X-ray diffraction were used to investigate the mechanism.It was found that Bronsted acid has a certain influence on Lewis acidity of titanium metal center though coordination,thus confirming the essence of binary acids cooperative catalysis.This paper mainly includes the following three parts:(1)We develop the synthesis of 1,2-disubstituted benzimidazole from aldehyde and o-phenylenediamine through condensation and cyclization catalyzed by Cp2TiCl2 and 3-hydroxy-2-naphthoic acid.This reaction was carried out with only 1 mol%of Cp2TiCl2 and 2 mol%3-hydroxy-2-naphthoic acid at 50? for one hour,ethanol as solvent,to obtain 17 cases of 1.2-disubstituted benzimidazoles with high yield up to 96%.The mechanism study by in-situ NMR titration and ESI-MS showed that the catalytically active species[Cp2Ti(?2-OC10H6CO2)]was formed in-situ in the catalytic system.The crystal was prepared and studied by X-ray diffraction.Further analysis indicated that the reaction undergoes an imine intermediate,and Cp2TiCl2/3-hydroxy-2-naphthoic acid catalyze the formation of target molecule from imine and aldehyde.(2)A method for preparing 1,5-benzodiazepines catalyzed by Cp2TiCl2 and L-threonine from o-phenylenediamine and ketone was developed.The reaction process was green and efficient under the solvent-free condition,and was carried out at 50-70? for several hours with only 2 mol%Cp2TiCl2 and 2 mol%L-threonine as catalyst.14 cases of 1,5-benzodiazepines was obtained with high yield up 100%.Related mechanism studies show that L-threonine can coordinate with Cp2TiCl2 during the reaction to form a catalytically active substance[CpTi(C4H7NO3)]+.By comparing catalytic systems of Cp2TiCl2/3-hydroxy-2-naphthoic acid and Cp2TiCl2/L-threonine,it was found that their difference in catalytic effect was mainly due to the influence of ligand effect on the Lewis acidity of titanium center.The reaction also undergoes an imine intermediate and Cp2TiCl2/L-threonine primarily catalyzed the formation process of final product from imine and ketone.(3)We synthesis the benzothiazoles by condensation and cyclization of o-aminothiophenol and benzaldehyde catalyzed by Cp2TiCl2 and 5-sulfosalicylic acid.The reaction was carried out with only 1 mol%Cp2TiCl2 and 2 mol%5-sulfosalicylic acid in ethanol at 60-70? for 2 hours,and obtained 13 case of benzothiazoles with a yield between 68%-95%.Through the screening of Bronsted acid,the effect of acidity and substituent electronic effect of benzoic acids,salicylic acids,amino acids and derivatives on Cp2TiCl2 catalytic activity were analyzed.