Synthetic Studies toward 3-(Acylamino)-1H-indazoles and Development of a One-Pot, Microwave-Assisted, Oxadiazole Condensation/Boulton-Katritzky Rearrangement

Abstract

Studies on the Boulton-Katritzky rearrangement of 3-(2-aminoaryl)-1,2,4-oxadiazoles have led to the identification of additional electronic factors that govern the rearrangement as well as a competitive thermal rearrangement pathway for select substrates. To circumvent the limitations of the conventional thermal conversion sequence an improved protocol that employs microwave irradiation has been devised that allows access to rearrangement products in good to excellent isolated yields. Furthermore, we have developed a two-component, one-pot sequence using a microwave-assisted oxadiazole condensation/Boulton-Katritzky rearrangement to deliver 3-(acylamino)-1H-indazoles from simple esters and 2-amino-N-hydroxy-benzamidine

Key words

Boulton-Katritzky rearrangement - indazole - microwave-assisted - oxadiazole condensation - substituent effects

References and Notes

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10

An alternative mechanism suggested by a reviewer involves protonation of the oxadiazole which promotes the observed rearrangement as shown below (Scheme  [4] ).

11

Heating was performed in a CEM Discover^® microwave for organic synthesis at 300 W for the time indicated with a ramp time of 2 min with a vertically focused IR temperature sensor.