Silver-Catalyzed Carboxylative Cyclization Of Alkynic Hydrazones With Carbon Dioxide

Catalytic transformation of carbon dioxide into valuable chemicals has been gaining much attentions since carbon dioxide is an abundant,inexpensive and renewable C1 feedstock.Nitrogen heterocyclic compounds are important structural units in biologically and pharmaceutically active molecules.Using carbon dioxide as an electrophile and nitrogen-containing compounds as a nucleophile to initiate cyclization reaction is the most common and effective method to construct nitrogen heterocyclic compounds containing carbonyl group.1,3,4-Oxadiazin-2-one is important structural subunit found in many biologically active compounds,and used as 1,2-diaza-1,3-butadiene precursors for the construction of other fine chemicals.Traditional synthetic methods including multi-step reactions show low efficiency.Therefore,it is very important to develop a more efficient and atomic economy method using carbon dioxide as carboxylation reagent.This thesis developed a new silver?I?-catalyzed carboxylative cyclization reaction of alkynic hydrazones with carbon dioxide under mild reaction conditions to construct 1,3,4-oxadiazin-2-one compounds.The cyclization reaction of phenylpropynal 2-hydroxyethylhydrazone with carbon dioxide was chosen as model reaction to identify the optimal conditions.Through the investigation of catalysts,bases,solvents,the pressure of carbon dioxide,the optimized reaction conditions were identified as follow:AgOAc?5 mol%?as catalyst,Cs₂CO₃?5 mol%?as base in DMSO at 25 ^oC for 2 h.Under optimal conditions,a series of 1,3,4-oxadiazin-2-ones containing different substituents were obtained in 54%-90%yield.This reaction maintained its high efficiency in the gram-scale reaction.According to the single-crystal X-ray analysis and NOE experiments,the geometries of the newly formed C=C bonds in 1,3,4-oxadiazin-2-ones products were identified to be Z isomers.Based on the control experiments and NMR studies,a mechanism including the formation of reactive carbazate intermediate,electrophilic cyclization to give vinyl silver intermediates and followed protonation was proposed.In summary,this dissertation developed a new silver?I?-catalyzed carboxylative cyclization reaction of alkynic hydrazones with carbon dioxide under mild reaction conditions,which offered a convenient and efficient method to synthesize 1,3,4-oxadiazin-2-one compounds.