A Theoretical Study On Several Important Fluorination Reactions

Introduction of a fluorine atom into the molecular structure of a compound will change its physicochemical properties and improve its pharmacological activities.However,natural fluorine-containing organic compounds are rare in nature.Therefore,introduction of fluorine atoms or fluorine-containing groups into organic molecules is an important issue in organic fluorine chemistry.Fluorinated compounds have become the products with high value-added,high-tech content,the most technologically promising and developmental advantages in the fields of pesticides,biomedicine,and materials.Traditional fluorination reactions are limited to small molecules,and reaction reagents are difficult to handle.Transition metal complexes and N-F reagents often participate in fluorination reactions with mild reaction conditions,good selectivity and low energy barrier.However,the bond between metal and fluorine is stronger,and compared with its larger molecular weight,fluorine content is much lower for the N-F reagents.Therefore,theoretical calculation on designing suitable catalysts and N-F reagents to reduce the reaction energy barrier of C-F bonds formation has attracted much attention.The microscopic reaction mechanism of four meso-substituted manganese porphyrins with cyclohexyl radical fluorination reaction was studied by using the Gusssian 09 program and density functional theory.The stable point geometry of the four reaction channels was optimized,the thermodynamic parameters and kinetic parameters of each reaction channel were obtained,and the potential energy surface information of each reaction channel was obtained too.The calculation results show that when the four kinds of manganese porphyrin capture cyclohexyl radicals,the Gibbs free energy of each point is less than zero,and the reaction can proceed spontaneously.The fluorination reaction involving Mn（TNαP）FCl has a lower reaction energy barrier and the lowest Gibbs free energy,and is a kinetic and thermodynamic dominant reaction channel.The effect of solvation on the fluorination reaction was investigated using the SMD solvation model.The results show that the reactivity of the four manganese porphyrins in the acetonitrile solvent is consistent with the trend of the reactivity in the gas phase.Thefluorinationreactionsofmonosubstitutedanddisubstituted N-fluoropyridine tetrafluoroborates with benzene in acetonitrile solution were studied using the Gaussian 09 program.The fluorination reaction activities of benzene with chloro,cyano,nitro,and methoxy substituted N-fluoropyridinium tetrafluoride salts at different reaction sites were compared.The results show that in the reaction system of monosubstituted N-fluoropyridine tetrafluoroborate and benzene,the nitro-substituted N-F reagents have the strongest fluorination abilities and the lowest reaction energy barriers;the methoxy-substituted N-F reagents have the weakest fluorination abilities and the highest reaction energy barriers.The ortho-substituted N-F reagents have the highest reactivities,while the para-position is just the opposite.The fluorination ability of the N-F pyridine fluorination reagent is positively correlated with the electron withdrawing ability of the substituents on the pyridine ring,that is,OCH₃<Cl<CN<NO₂.Among the monosubstituted N-fluoropyridine boron tetrafluoride salts,oNO₂NFpyr has the strongest fluorination ability.Results of disubstituted N-F reagents indicated that the nitro-substituted disubstituted N-fluoropyridine tetrafluoroborates have the strongest fluorination abilities,and the methoxy group is on the countary.The 6-substituted disubstituted N-fluoropyridine tetrafluoroborates have the highest fluorination activities,and the4-position substitution is just the opposite.The fluorination capacity follows the trend of the electron-withdrawing ability of the substituent.2,6-dinitro-substituted N-fluoropyridine tetrafluoroborates has the best fluorination ability.The introduction of chloro,cyano and nitro groups can increase the fluorination reactivity of the N-fluoropyridine tetrafluoroborates with benzene.Through the research in this thesis,the fluorination reaction mechanism of the manganese porphyrin with cyclohexane radical was clarified by the substituent effect and the electron effect.The mechanism of fluorination reaction of N-fluoropyridinine tetrafluoroboronates with benzene was clarified.It provides a reliable theoretical basis for further screening and design of high-efficiency N-F reagents and manganese porphyrin catalysts.It provides support for further research on the mild fluorination reaction of organic molecules.