| Free radical chemistry which has been developed for more than a century,gain great attention from researchers.Free radical type reactions usually exhibit many advantages,such as high reactivity,mild conditions,high atom economy and step economy,therefore these reactions are often applied to research areas such as biomedicine,organic synthesis,and materials science.Especially in recent years,the development of free radical initiation methods such as transition metal catalysis,photocatalysis and electrocatalysis has greatly enriched the types of free radicals and expanded the development space of free radical reactions.Thus,free radical reactions provided a more convenient and quick protocol for the design of complex drug molecules and the total synthesis of natural products.Considering that heterocyclic molecular skeletons widely exist in biologically active pharmaceutical molecules and natural products,the application of free radical type reactions to the functionalization and derivatization of compounds containing heterocyclic molecular skeletons is not only of great significance in the field of organic synthesis,but also exhibit potential application value in pharmaceutical industry.Based on the characteristics of free radical reactions as well as the unique structure of heterocyclic compounds,and combining the concept of green chemistry,the following two parts are included in this paper:1.Azidation reaction of 3-hydroxybenzothiophene compounds under copper catalysis.Organic azide compounds are an important class of intermediates in organic synthesis.As nitrogen-containing precursors,they can be easily converted into other functional molecules,such as amines,amides,imines,aziridines,and triazoles.In this paper,the azidation reaction of 2-phosphono-3-hydroxybenzothiophene was successfully achieved with Cu/TBHP system,and a possible reaction mechanism was proposed.The introduction of azide groups,while retaining the molecular heterocyclic structure,constructed the quaternary carbon center,which provides the possibility for further synthesis of bioactive molecules.The method shows good functional group tolerance with mild reaction conditions and has moderate to excellent yields.A total of 19 compounds were synthesized,all of which are new compounds that have not been reported before in literature.The compounds were fully characterized by nuclear magnetic resonance spectroscopy(1H-NMR,13C-NMR,31P-NMR)and mass spectrometry(HRMS).In addition,this article also successfully achieved the conversion of azide functional groups to amino groups,which laid foundation for further application of the products.2.Study on the direct cross-coupling of thiazole derivatives and diarylphosphine oxide to form C-P bonds under electrocatalytic conditions.Organophosphorus compounds are the basic structure that constitutes a living body,and they are widely used in the fields of catalysis,pesticides,biomedicine,material chemistry,organic synthesis,etc.Therefore,efficient construction of C-P bonds is crucial.Traditional methods for the construction of C-P bonds usually require the addition of transition metals,large amounts of oxidants,or other harsh reaction conditions such as high temperatures and toxic solvents.Compared with traditional synthetic methods,organic electrochemical synthesis is more consistent with the concept of green chemistry.In this work,phosphono functional group was introduced to the 2-position of the thiazole compound to synthesize a series of 2-phosphonothiazole derivatives,and a possible reaction mechanism was proposed on the basis of experimental results and literature research.The reaction system with mild conditions avoids the addition of metal catalysts or external oxidants,provides moderate to good yield and the functional groups are well tolerated.A total of 16 target compounds were synthesized,which were characterized by nuclear magnetic resonance spectroscopy(1H-NMR,13C-NMR,31P-NMR). |
