Synthesis, alkylation, reduction and acylation of halo-functionalized isatins

Abstract

In this paper, 4-haloanilines were first underwent the Sandmeyer reaction to give the corresponding halo-functionalized isatins 3a~3c, which were further alkylated at the nitrogen atom to give 4a~4o followed by in situ reduction using hydrazine hydrate to obtain the oxindole products 5a~5o. 5a~5o were subjected to the acetylation reaction by the treatment with acetic anhydride in the presence of a catalytic amount of N,N-dimethylaminopyridine to afford the intermediates of 2-acetoxy-3-acetylindoles, which were used in next step without further purifucation. Subsequently, the hydrolysis reaction of the arising ester functions of the intermediates was carried out in tetrahydrofuran (THF) with the presence of 5% aq. NaOH at room temperature to give the targeted compounds 6a~6o. Some compounds synthesized are novel. Their structures were confirmed by 1H NMR, 13C NMR, IR, MS and elemental analysis. © 2014 Chinese Chemical Society & SIOC, CAS.