One-pot carbonylation-dehydration tandem reaction of aryl iodides with acylhydrazines for synthesis of 2,5-diaryl-1,3,4-oxadiazoles

The structures of 2,5-diaryl-1,3,4-oxadiazoles with good stability have attract great attention for development of new and safe therapeutic agents with functions in antimicrobial, anti-inflammatory, antitumor, and antiviral (for treatment of HIV infection), etc. In the present work, over the developed Pd-catalytic system with involvement of the 3-thiophenyl-benzimidazolyl-based mono-phosphine, the one-pot carbonylation-dehydration tandem reaction of aryl iodides with acylhydrazines for synthesis of 2,5-diaryl-1,3,4-oxadiazoles was reported for the first time with advantages of simplified manipulations, high efficiency (yields of 62–93%), as well as high safety of applied organic substrates. The relatively high reaction temperature of 140–160 ℃ was required for this tandem reaction, wherein the good stability of the involved phosphine with suitable stereo-electronic property guaranteed the fulfilment of this sequence. It was demonstrated that the first-step carbonylation of aryl iodides with acylhydrazine toward N,N′-diarylhydrazides was the rate-determine step in the overall process. Subsequently, the formed N,N'-dibenzoylhydrazides irreversible dehydrated into 2,5-diaryl-1,3,4-oxadiazoles with the presence of dehydrating agent like DCC. Graphical abstract: [Figure not available: see fulltext.]