950272-35-2Relevant academic research and scientific papers
Electrophilic activation of nitroalkanes in efficient synthesis of 1,3,4-oxadiazoles
Aksenov, Alexander V.,Khamraev, Vladislav,Aksenov, Nicolai A.,Kirilov, Nikita K.,Domenyuk, Dmitriy A.,Zelensky, Vladimir A.,Rubin, Michael
, p. 6636 - 6642 (2019/03/14)
A novel methodology for general and chemoselective preparation of non-symmetric 1,3,4-oxadiazoles is developed. This unusual reaction proceeds via polyphosphoric acid-assisted activation of nitroalkanes towards nucleophilic attack with acylhydrazides.
A convergent synthesis of 1,3,4-oxadiazoles from acyl hydrazides under semiaqueous conditions
Tokumaru, Kazuyuki,Johnston, Jeffrey N.
, p. 3187 - 3191 (2017/04/04)
The 1,3,4-oxadiazole is an aromatic heterocycle valued for its low-lipophilicity in drug development. Substituents at the 2- and/or 5-positions can modulate the heterocycle's electronic and hydrogen bond-accepting capability, while exploiting its use as a carbonyl bioisostere. A new approach to 1,3,4-oxadiazoles is described wherein α-bromo nitroalkanes are coupled to acyl hydrazides to deliver the 2,5-disubstituted oxadiazole directly, avoiding a 1,2-diacyl hydrazide intermediate. Access to new building blocks of oxadiazole-substituted secondary amines is improved by leveraging chiral α-bromo nitroalkane or amino acid hydrazide substrates. The non-dehydrative conditions for oxadiazole synthesis are particularly notable, in contrast to alternatives reliant on highly oxophilic reagents to effect cyclization of unsymmetrical 1,2-diacyl hydrazides. The mild conditions are punctuated by the straightforward removal of co-products by a standard aqueous wash.
High-temperature continuous flow synthesis of 1,3,4-oxadiazoles via N-acylation of 5-substituted tetrazoles
Reichart, Benedikt,Kappe, C. Oliver
supporting information; experimental part, p. 952 - 955 (2012/03/11)
Applying continuous flow processing in a high-temperature/high-pressure regime (200-220 °C, 11-14 bar) 2,5-disubstituted-1,3,4-oxadiazoles are prepared in high yields within 5-10 min residence time by treatment of 5-substituted-1H-tetrazoles with anhydrides or acid chlorides as electrophiles (Huisgen reaction).
