Rapid Boulton–Katritzky rearrangement of 5-aryl-3-[2-(piperidin-1-yl)ethyl]-1,2,4-oxadiazoles upon exposure to water and HCl

Abstract

Сhemical stability of 3-(2-aminoethyl)-5-substituted 1,2,4-oxadiazoles was studied with respect to Boulton–Katritzky rearrangement, which is known to produce planar pyrazolines and pyrazoles upon heating in DMF at 150°C or without solvent at 240°C. The reactivity of 5-aryl-3[2(piperidin-1-yl)ethyl]-1,2,4-oxadiazoles in one type of Boulton–Katritzky rearrangement was observed at room temperature in H 2 O, DMF + H 2 O, and in the presence of HCl. Hydrolysis of 3,5-disubstituted 1,2,4-oxadiazoles under the first two conditions gave 2-amino-1,5-diazaspiro[4.5]dec-1-en-5-ium benzoates, while the action of HCl on 3,5-disubstituted 1,2,4-oxadiazoles produced their hydrochlorides along with 2-amino-1,5-diazaspiro[4.5]dec-1-en-5-ium chloride hydrate. Thus, the reaction afforded spiropyrazoline compounds instead of products with a planar structure.