Synthesis Of 2-Amino-1,3,4-Oxadiazoles/Thiadiazoles Via Sequential Condensation And I₂-Mediated Oxidative C-O（S） Bond Formation

Heterocyclic compounds not only have a wide range of biological activity and industrial application, but also play a vital role in the development of human society. Consequently, construction of heterocyclic skeletons has received considerable attention from chemists. Among numerous synthetic methods, the ones via intramolecular oxidative C-Y(N, O, S, etc.) bond formation strategy are getting more and more popular. So far there are several approaches to approach this: 1) catalyzed by transition-metal(e.g. Pd, Cu, etc.), the acyclic substrates are oxidized by certain oxidants to form intramolecular C-Y bonds; 2) direct oxidation of acyclic precursors affords the corresponding heterocyclic compounds by oxidants, such as, hypervalent iodine reagents, Br2, Mn reagents and DDQ etc. 3) there are also some other synthetic methods for heterocyclic synthesis, such as electrocyclic reactions.With the development of organic chemistry, there is a trend to develop eco-friendly new synthetic methodologies using reagents with low toxicity. As a mild oxidant with low toxicity, molecular iodine has been extensively used in a variety of organic synthesis reactions. In this dissertation, we established a new I2-mediated synthetic methodology for the construction of intramolecular C-O/C-S bond in the presence of base. This reaction has been successfully applied for the synthesis of 5-substituted-1,3,4-oxadiazol-2-amine and 5-substituted-1,3,4-thiadiaz- ol-2-amine deravitives: After the completeness of condensation of aldehydes and aminourea/thiosemicarbazide, the solvent was evaporated under reduced pressure. The resulting residue was re-dissolved in 1,4-dioxane, followed by addition of potassium carbonate and iodine in sequence. The oxidative cyclization was completed under mild reaction conditions and yielded eighteen 2-amino-1,3,4- oxadiazoles and twelve 2-amino-1,3,4-thiadiazoles.This versatile and transition-metal-free protocol allows the efficient synthesis of a variety of aryl-, alkyl-, and alkenyl-substituted diazole derivatives bearing a 2-amino group in a scalable fashion.