138723-97-4Relevant academic research and scientific papers
Batch Versus Flow Lithiation–Substitution of 1,3,4-Oxadiazoles: Exploitation of Unstable Intermediates Using Flow Chemistry
Wong, Jeff Y. F.,Tobin, John M.,Vilela, Filipe,Barker, Graeme
supporting information, p. 12439 - 12445 (2019/09/06)
1,3,4-Oxadiazoles are a common motif in pharmaceutical chemistry, but few convenient methods for their modification exist. A fast, convenient, high yielding and general α-substitution of 1,3,4-oxadiazoles has been developed using a metalation-electrophilic trapping protocol both in batch and under continuous flow conditions in contradiction to previous reports which suggest that α-metalation of this ring system results in ring fragmentation. In batch, lithiation is accomplished at an industrially convenient temperature, ?30 °C, with subsequent trapping giving isolated yields of up to 91 %. Under continuous flow conditions, metalation is carried out at room temperature, and subsequent in flow electrophilic trapping gave up to quantitative isolated yields. Notably, lithiation in batch at room temperature results only in ring fragmentation and we propose that the superior mixing in flow allows interception and exploitation of an unstable intermediate before decomposition can occur.
Electrooxidative Cyclization of N-Acylhydrazones of Aldehydes and Ketones to Δ3-1,3,4-Oxadiazolines and 1,3,4-Oxadiazoles
Chiba, Toshiro,Okimoto, Mitsuhiro
, p. 1375 - 1379 (2007/10/02)
The electrolytic oxidation of ketone N-acylhydrazones (1) in methanolic sodium acetate induced their intramolecular cyclization to the corresponding 2-methoxy-Δ3-1,3,4-oxadiazolines 3.The thermal stability of a given oxadiazoline and what products were formed by its thermal decomposition was found to depend on the natures of the substituents at C-2.Thus, 2-methoxy-2-phenyloxadiazolines preferentially yielded oxiranes 5, whereas 2-alkyl-2-methoxyoxadiazolines preferentially gave enol ethers 6. 2,2-Dimethoxyoxadiazolines decomposed to the parent ketones and many unidentified products.The electrolytic oxidation of aldehyde N-acylhydrazones 2 gave 2,5-disubstituted 1,3,4-oxadiazoles 4.The oxidative cyclization of the N-benzoylhydrazones of aliphatic aldehydes gave especially high yields of the corresponding heterocycles.
