New Synthetic Method Of 1,3,4-thiadiazoles And Pyrrolidone Derivatives

Thiadiazole derivatives are a kind of representative five-carbon nitrogen heterocycle compounds,of which 1,3,4-thiadiazole are a kind of thiadiazole derivatives with high biological activity,which not only have a variety of biological activities,including adenosine histamine receptor antagonist,anti-diabetes,anti-depression drugs and anti-cancer activity,they are also widely used in materials science and heterocyclic synthesis by fusion with peptides.Pyrrolidone derivatives have good pharmacological and biological activities in anti-tuberculosis,antibacterial,antifungal and anti-tumor,and are also widely used in material science,life science,organic chemistry and other fields.In this paper,a new one-pot four components synthesis of 2,5-disubstituted 1,3,4-thiadiazoles by a cascade Ugi/aza-Wittig process has been developed,starting from the(N-isocyanimino)triphenylphosphorane,aldehydes,amines and thioacids;Two types of pyrrolidone compounds were highly selective synthesized by continuous Ugi 4CR/nucleophilic addition.The details are as follows:1.The synthesis method of 2,5-disubstituted-1,3,4-thiadiazole and pyrrolidines and the latest research progress of conventional Ugi multi-component reaction and aza-wittig reaction are reviewed.2.A four-component cascade Ugi/aza-Wittig reaction was conducted between(N-isocyanimino)triphenylphosphorane as isonitrile,aldehydes,amines and thioacids,and 2,5-disubstituted 1,3,4-thiadiazole was obtained by one-pot synthesis.The synthesis route is as follows:3.The allenoic acid is formed by bromoalkyl chloride,which was used as the acid component,ketoaldehyde was synthesized from bromoacetophenone,which was used as the aldehyde component,pyrrolidone and pyrrolidone compounds were prepared by a Ugi/intramolecular nucleophilic addition sequence starting from the allenoic acid,ketoaldehyde,amine and Isocyanide,occurred at room temperature.When R2=Alkyl or R2=R3=H,the target product pyrrolidone 10 is directly produced by a one-pot method.When R2=H,R3=Alkyl,the resulting compound 10 further undergoes continuous double bond isomerization/dearoylation reaction to obtain a pyrrolidone derivative 11.The synthesis route is as follows:...