Synthesis And Application Of Multifutionalized Benzyne

Benzyne is one of the most active species in synthetic chemistry at present.As an important class of electrophilic intermediates with high activity,it is widely used in the synthetic research on natural products,medicines,ligands and materials.In recent decades,a large number of chemical reactions involving benzyne have been developed,such as cycloaddition reactions,multi-component reactions,and insertion reactions.Through these reactions,aromatic fused ring compounds and multifunctionalized aromatic compounds can be constructed effectively.Preparation of polyfunctionalized benzyne precursors and their application in the selective synthesis of fused ring compounds have been studied in this thesis.Part one:Selective synthesis of sulfonic acid（halophenyl）estersAccording to the different types of substituents on the benzene ring,different experimental schemes were used to construct several different types of sulfonyloxyhalobenzenes as phenylyne precursors.Selective one-sided hydrolysis of2,6-bis（p-tolyl）sulfonyloxy was realized for the first time in the process,in which the nuclear magnetic purity of the hydrolysate is over 99%.The synthesized products were confirmed by IR,¹H NMR,¹³C NMR and HRMS.Part two:Study on the Synthesis of Benzocyclobutene DerivativesIn the presence of organolithium reagent,the sulfonyloxyhalobenzene provided the benzyne which underwent selectively a[2+2]cycloaddition reaction with the enol anion to produce benzocyclobutenol.It was found that the regioselectivity of the cycloaddition is obviously affected by the type substituents of the benzene.which provides ideas and methodologies for the selective construction of multifunctionalized molecules.The products were confirmed by IR,¹H NMR,¹³C NMR and HRMS.Part three:Selective Synthesis of Polyhalohydroxy Diaryl EthersPolyhalogenated hydroxydiaryl ethers are not only a class of compounds with bacteriostatic effect,but the functional groups in the aromatic rings also provide multiple opportunities for the derivatization of aromatic hydrocarbons.Using 2-fluoro-6-bromotoluene as starting material,polyhalohydroxydiaryl ethers were selectively synthesized via the process including oxidation,selective nucleophilic substitution on aromatic ring,Baeyer-Villliger oxidation,and hydrolysis,etc.All the products were verified by IR,¹H NMR,¹³C NMR,HRMS.Some of the synthesized compounds showed plausibly antibacterial activity.Part four:Synthesis of dibenzofuran compoundsSulfonylation of the polyhalogenated hydroxydiaryl ether led to the formation of the bezyne precursor with multiplely active centers.Under alkaline conditions,a Domino process was carried out in which the intramolecular nucleophilic addition of phenyl anion to the triple bond of benzyne generated the dibenzofuran skeleton followed by the formation of a sequensary anion adjacent to the new C-C bond.As an active center formed in situ,the phenyl anion could be converted for further functionalization.The reaction is being optimized through substrate designing and alkali screening.Possible mechanism was proposed.The products were confirmed by IR,¹H NMR,¹³C NMR,MS and HRMS.