Study On The Synthetic Methods Of Nitrogenous Compounds From Guanidines And Cyclic Peroxides

Organic nitrogen-containing compounds can be widely found in biologic and pharmaceutical molecules.Therefore,the synthesis of organic nitrogen-containing compounds has received extensive attention,especially the synthetic methods which using abundant biomass carboxylic acid derivatives as starting materials.This dissertation developed three synthetic strategies using carboxylic acid derived aromatous guanidines which containing N,O heteroatoms with symmetrical framework,and cyclic diacyl peroxides as starting materials.A series of nitrogen-containing compounds high structural diversity and broad substrate applicability,were obtained under mild reaction conditions.This dissertation contains three parts:the metal-mediated degradation of guanidine derivatives,the metal-free formation of cycloalkynes,and in situ difunctional halogenating reagents system.Inspired by the enzyme promoting biometabolic transformation from guanidines to peptides,we used the CO/Pd?OAc?₂/Cu?OAc?₂ system to achieve the direct chemical transformation of two important nitrogen-containing compounds from aromatous guanidines to acetanilides.This method showed great functional group compatibility,and substrates with various kinds of functional groups such as alkyl,halogen,acyl,alkoxyl,thioether,and trifluoromethyl were degraded to corresponding anilide products up to 89%yield.By changing Cu?II?carboxylates,corresponding N-acylation products were obtained,such as acetyl,propionyl,formyl,and benzoyl groups.Mechanism investigation revealed the catalytic cycle of palladium diacetate with Cu?II?carboxylates serving as both acylating agents and oxidants in cleavage and formation of N-?C=N?and N-CN in guanidines.Under the UV illumination,cyclic maleoyl peroxide generated highly reactive benzyne and strained six-membered cycloalkyne intermediate after decarboxylation process,which was used to synthesize a series of triazol type of nitrogen-containing compounds.With 1,2-dichloroethane as solvent,eight phthaloyl peroxide derivatives?benzyne precursors?reacted with ten azides to produce corresponding benzotriazoles.In addition,after screening the reaction conditions,this dissertation first reported aliphatic maleoyl peroxide,which served as six-membered cycloalkyne precursors under 350 nm UV illumination,underwent[3+2]cycloadditions at room temperature with fifteen organic azides,and selectively afforded the corresponding benzotriazoles up to 99%yields within two hours.This reaction was compatible well with active hydrogens and unsaturated bonds,and azides bearing functional groups like amides and olefins afforded the corresponding cycloaddition products in good yields under this reaction conditions.Besides,the cycloalkyne precursors could be synthesized in gram level by 2-3 steps under mild reaction conditions and column-free set up with just CO₂ as a by-product.The combination of cyclic diacyl peroxides and halide salt forms an unreported difunctional halogenating agents,which was successfully used in the Hofmann-L?ffler-Freytag reactions of sulfonamide compounds and the intramolecular halogen hydroxylation cyclizations,affording a series of nitrogen-containing compounds.In the aspect of Hofmann-L?ffler-Freytag reactions,when using different halide sources,sulfonamide?as starting materials?generated the radical intermediates,and formed 13 N-chloroamides,16?-C?sp³?brominated and iodinated products,and even 11 pyrrolidine derivatives in moderate to excellent yields?up to 99%?.When tetrabutyl ammonium chloride?TBACl?was used,both aliphatic and aromatic sulfonamides can produce corresponding products,such as p-tolylsulfonyl,p-nitrobenzenesulfonyl,and methanesulfonyl substrates.When tetrabutylammonium bromide?TBAB?was used,the sulfonamide?starting materials?directly produced?-brominated products by 1,5-hydrogen atom transfer?HAT?process.When there was C-H bonds on?or?sites in substrates,just?-brominated products were generated.When Cs I was used as a halide source,the addition of 1equiv sodium acetate could remarkably improve yields of products.The radical inhibition experiments demonstrate that the?-bromination and cyclizations forming pyrrolidines may involve radical processes.The NMR test and single-crystal structure analysis of the by-product were used to determine the structures of halogenating reagents.In the aspect of intramolecular halogen hydroxylation cyclizations,phthaloyl peroxides combined with tetrabutyl ammonium halide to realize Cl,Br,I participated cyclizations by ion mechanism with yields up to 90%.