Titanocene-catalyzed Biginelli Reaction And Palladium-catalyzed Urea Carbonylation Reaction

Urea and its derivatives have attracted much attention because of their wide applications in industry,agriculture,medicine and daily life.The traditional methods for the synthesis of urea derivatives usually have drawbacks of the high toxicity of substrates,poor catalyst activity,and poor substrate suitability.Therefore,the development of new and highly efficient catalytic synthesis method of urea derivatives is imperative.This dissertation aims to solve the problems encountered in the synthesis of urea derivatives.Based on the previous work in our group,two highly efficient catalytic systems have been developed to synthesize dihydropyrimidinone derivatives and acylurea compounds by using Cp2TiC12 and Pd(OAc)2 as precatalysts,respectively.Additionally,the coresponding reaction mechanism was explored by in situ NMR,ESI-MS,ESI-MS/MS,and X-ray single crystal diffraction.The main contents of this thesis include:1.A new model for high-efficiency Ti(IV)catalysts was developed by in situ activation of the precatalyst,Cp2TiC12,with urea molecule The new catalytic system can efficiently catalyze the Biginelli reaction of aldehydes,urea and 1,3-diketonates under milder conditions to get dihydropyrimidinone derivatives as product,18 examples was shown with a maximum yield of 93%.Mechanism research revealed that urea act as a base to effectively regulate the Lewis acidity of Cp2TiC12 in this system.Furthemore,the urea also coordinated with titanium as a ligand to form a highly efficient active species[(MeO)2Ti(NHCONH2)]+,which promotes the dehydration of urea and aldehyde to form an imine.Ultimately,the imine cyclized with a 1,3-diketone to obtain the target molecule.2.A transition metal palladium catalyzed urea carbonylation reaction was developed by coupling urea and aryl halide compounds,with Fe(CO)5 as the carbonyl source.The method was mild and efficient.The method avoided the use of highly toxic CO and did not require the addition of ligands,and the substrate tolerance was good.33 examples were obtained with a maximum yield of 98%.Of the examples,five new acylurea compounds were reported firstly,and two examples were bilateral carbonylation products.The reaction system can be applied to different types of substrates including aryl,alkyl,heterocyclic,and polycyclic aromatic hydrocarbons.The experiment results indicated that it tend to obtain double carbonylation substitution product instead of the single one when the conjugated substrate participates in the reaction.