Synthesis Of Isatoic Anhydride Via Cyclization Reaction Jointly Using Carbon Dioxide And Carbon Monoxide

As an abundant,readily available and renewable carbon resource,carbon dioxide conversion into valuable chemicals have gained more and more scholars'attentions to meet the demand of sustainable development of the society.At present,many organic reactions to consturct various heterocyclic compounds using carbon dioxide have been reported,but reports on the synthesis of cyclic anhydrides using carbon dioxide are very limited.In view of the importance of cyclic anhydride compounds in organic synthesis,it's necessary to explore an efficient method to selectively synthesize cyclic anhydrides using carbon dioxide as a reagent.Isatoic anhydride is a very important organic intermediate and is widely used in the fields of biology and pharmacology.Traditional synthesis methods,such as cyclization reactions of anthranilic acid,oxidative reactions of isatins,often involve the uses of highly toxic reagents such as phosgene or stoichiometric oxidants.For the viewpoint of green chemistry,it is necessary to develop a transition-metal-catalyzed method for the synthesis of isatoic anhydride that is simple,efficient and redox-neutral.Therefore,this thesis mainly focus on developing a highly selective palladium-catalyzed cyclization reaction for preparing a broad range of substituted isatoic anhydrides in good to excellent yields from o-iodoaniline,CO₂ and CO.The cyclization reaction of o-iodoaniline with CO₂ and CO was initially used as a model reaction.Through the investigation of palladium catalysts,bases,solvents,temperatures,pressure and so on,the optimized reaction conditions were identified as follow:Pd?PPh₃?₄?1.0 mol%?as catalyst,CsOAc?1.0 equiv.?as base in THF at 60 ^oC for 16 h.Under optimal conditions,32 kinds of o-iodoaniline compounds containing different substituents can react with CO₂ and CO to obtain the corresponding isatoic anhydride products in high yields,which can be easily converted into other useful organic intermediates through some simple organic reactions.The sources of the two carbonyl groups in the products were determined by isotopic labeling experiments.The carbonyl group in the carbamate moiety came from CO₂,while the carbonyl group linked to the aryl ring derived from CO,indicating that CO₂ and CO were indispensable in the process for synthesis of isatoic anhydrides.The possible catalytic cycle mechanism of this reaction was proposed:o-iodoaniline first underwent oxidative addition of Pd⁰ and then CO insertion gave acyl palladium intermediate,which underwent reaction with CO₂ in the presence of base to form acyl palladium carbamate,subsequent reductive elimination provided isatoic anhydride products.In summary,this dissertation developed an effective method for palladium-catalyzed cyclization reaction for preparing isatoic anhydrides from o-iodoaniline with CO₂ and CO under redox-neutral and mild reaction conditions.