Synthesis Of Thioamides And Heterocyclic Compounds Containing Sulfur

Thioamides and heterocyclic compounds containing sulfur are prevalent structural motifsthat are found in many biologically active molecules. It has been demonstrated thatthioamides are useful synthons in many organic transformations. The synthetic methods ofthese compounds have attracted great interest in organic synthesis.The functionalizaton of alkynes and transition metal-mediated reaction to constructheterocycles have attracted considerable attention over the past decade. In particular, coppersalts have been successfully applied in formation C-hetero or hetero-hetero bonds, whichexhibit great potential for the construction of various heterocycles. To date, a range ofcopper-mediated methodologies aiming at affording heterocyclic compounds have beendeveloped.Our objectives are to develop catalytic system or transiton-metal-free conditions toselectively form C-N, C-S and N-S bonds to synthesize thioamides and heterocycliccompounds containing sulfur. Our research on synthetic methods of theses compounds led toa series of new results which will be presented in the following four chapters.In Chapter1, we have introduced the synthesis progress on thioamides,2-substitued benzothiazoles, thiadiazoles, and the synthesis methods of theses compoundsthough selective C-N, C-S and N-S bonds formation and introduces the significane of thisresearch subject.In Chapter2, we herein described a novel method for the synthesis of thioamides bythree component condensation of haloalkynes, amines, and Na2S·9H2O in the absence of anycatalyst. The C-N and C=S bonds of molecular products seclectively form thoughnucleophilic substituted and nucleophilic addition reaction respectively. The developedmethod is applicable for a wide range of amines including primary amines, secondary amines,third amines and haloalkynes including alkynyl bromides, alkynyl chlorides. The reactiveactivity of alkynyl bromides was higher than alkynyl chlorides. When alkynyl iodides wereused, they reacted with solvent DMF to form thioamides in low yield, which presumablyinvolved a radical process.In Chapter3, an efficient and convenient method was developed for the formation of 2-substituted benzothiazoles via a copper(II)-catalyzed condensation of2-aminobenzenethiolswith nitriles. The copper salt induced the sequential nucleophilic additions of–SH and–NH2of2-aminobenzenethiols with–CN of nitriles, and after releases NH3to generate2-substitutedbenzothiazoles. The developed method is applicable to a wide range of2-substitutedbenzothiazoles, aromatic nitriles, and aliphatic nitriles containing different functional groupsfurnishing excellent yields of the corresponding products. The ethanol as the environmentalfriendly solvent, the inexpensive catalytic system, mild conditions combined with anoperationally simple procedure render it a powerful component to traditional approaches forthe synthesis of biologically important compounds containing a benzothiazole framework.In Chapter4, a copper(II)-mediated homocoupling of thioamide for synthesis of3,5-disubstituted1,2,4-thiadiazoles has been reported. Under oxidative reaction conditions,thioamides could be transformed to nitriles via dehydrosulfurization, and thioamides could betransformed to3,5-disubstituted1,2,4-thiadiazoles via selective oxidative cyclization reaction,these were chemoseclective results with different oxidizing agents. We disclose a novelmethod for synthesis of3,5-disubstituted1,2,4-thiadiazoles via highly selective oxidativecyclization reaction of thioamides in the exist of copper salt and base. The copper salt wasused as Lewis acid activator and oxidizing agent in this reaction. In the course of C-N bandformation, the copper salt activated the C=N bond of isomerized thioamides. In the course ofN-S bond formation, the CuIIserved as oxidizing agents oxidized two nucleophilic centers.