Radical-mediated Synthesis Of 4-quinolone And Benzothiazole Derivatives And Development And Application Of Flow Cells For Electrosynthesis

The skeletons of organic compounds are mainly composed of C-C bonds,but their function are often accomplished by heteroatoms.Heterocyclic compounds are by far one of the largest class of organic compounds and are omnipresent in natural products,organic materials,agrochemicals and pharmaceuticals.In this thesis,a series of 4-quinolones and(aza)benzothiazoles were synthesized via nitrogen and sulfur radical species generated by oxidation.The development and application of flow electrochemical cells for organic synthesis have been investigated.First,an oxidative(3+2+1)cyclization of propargylanilides and CO has been developed for the synthesis of 4-quinolones.The method employs hypervalent iodine as the oxidant to cleave a N-H bond to afford amidyl radicals,which undergoes radical cascade reaction to give the targeted heterocycles(Scheme 1).Secondly,we report a metal-and reagent-free method for the uniform synthesis of benzothiazoles and thiazolopyridines through 2,2,6,6-tetramethylpiperidine-N-oxyl radical(TEMPO)-catalyzed electrolytic C-H thiolation(Scheme 2).This dehydrogenative coupling process provides access to a host of benzothiazoles and thiazolopyridines from N-(hetero)-arylthioamides.Mechanistic studies suggested that the thioamide substrate was oxidized with the electrochemically generated TEMPO+through an inner-sphere electron transfer to afford a thioamidyl radical,which undergoes homolytic aromatic substitution to form the key C-S bond.The method was applied in a broad substrate scope and functional group tolerance,particularly excellent for the synthesis of 2-alkyl(aza)benzothiazoles and pyridylthiazoles.In third part of this thesis,a catalyst-and supporting electrolyte-free method for electrochemical dehydrogenative C-S bond formation in continuous flow has been developed(Scheme 3).A broad range of N-arylthioamides have been converted to the corresponding benzothiazoles in good to excellent yields and with high current efficiencies.This transformation is achieved using only electricity and laboratory grade solvent,avoiding degassing or the use of inert atmosphere.This work highlights three advantages of electrochemistry in flow,which is(i)a supporting electrolyte-free reaction,(ii)an easy scale-up of the reaction without the need for a larger reactor and,(iii)the important and effective impact of having a good mixing of the reaction mixture,which can be achieved effectively with the use of flow systems.