Synthesis of 2-Amino-1,3,4-oxadiazoles and 2-Amino-1,3,4-thiadiazoles via Sequential Condensation and I₂-Mediated Oxidative C–O/C–S Bond Formation

Abstract

2-Amino-substituted 1,3,4-oxadiazoles and 1,3,4-thiadiazoles were synthesized via condensation of semicarbazide/thiosemicarbazide and the corresponding aldehydes followed by I2-mediated oxidative C–O/C–S bond formation. This transition-metal-free sequential synthesis process is compatible with aromatic, aliphatic, and cinnamic aldehydes, providing facile access to a variety of diazole derivatives bearing a 2-amino substituent in an efficient and scalable fashion.

1,2,4- and 1,3,4-Oxadiazoles as Scaffolds in the Development of Antiparasitic Agents

“…All tested molecules displayed antileishmanial activity, with IC 50 values ranging from 0.95 ± 0.01 μmol L -1 to 78.6 ± 1.78 μmol L -1 . Thirteen of them exhibited IC 50 values lower or comparable to pentamidine's (IC 50 = 7.02 μmol L -1 ). We selected for this review the seven most promising compounds (84a-g) based on their activity against L. major and calculated SI values.…”

“…We selected for this review the seven most promising compounds (84a-g) based on their activity against L. major and calculated SI values. With the exception of 84g, all these compounds presented low toxicity against U-937 and THP-1 cells (IC 50 ≥ 100 μmol L -1 ). Chemical structures of selected compounds with respective IC 50 values are shown in Table 13.…”

“…With the exception of 84g, all these compounds presented low toxicity against U-937 and THP-1 cells (IC 50 ≥ 100 μmol L -1 ). Chemical structures of selected compounds with respective IC 50 values are shown in Table 13. 72 Molecular docking studies were carried out on pteridine reductase (PTR1, PDB code: 1E7W).…”

“…Then, the oxadiazoles were reacted with the previously prepared S-alkyl-thioisothiourea intermediates (48), furnishing the disulfides (49) (Scheme 9). 48 In their investigation for antitubercular agents, Desai et al 49 49 Niu et al 50 used iodine to mediate the formation of C-O bond in a one-pot procedure. Aldehydes with different substitution patterns (54) were reacted with semicarbazide hydrochloride in the presence of sodium acetate in methanol/water.…”

“…The 1,3,4-oxadiazole derivatives (55) were obtained after 1-4.5 h at 80 °C, as shown in Scheme 11. 50 It is also possible to find protocols employing heterogeneous catalyst systems to obtain 1,3,4-oxadiazoles in one step. Sanghshetti et al 51 described the reaction of hydrazide (56) and several aroyl aldehydes (57) in the presence of nanoparticles of ZnO-TiO 2 under microwave irradiation, affording the respective 1,3,4-oxadiazoles (58).…”