An Efficient Synthesis of Mono‐ and Bis‐Indole Dioximes: Key Intermediates for the Design of Novel Nortopsentin Analogs

Abstract

AbstractA straightforward one‐pot synthesis method has been developed for combining the vic‐dioxime scaffold with the indole nucleus. Sixteen new mono‐ and bis‐indole dioximes were prepared as the first example of C−C coupling between readily available chloroglyoximes with indoles. This atom‐economic method requires only a stoichiometric amount of inexpensive sodium acetate and does not require any catalysts or toxic solvents. The reaction conditions were optimized and proceeded smoothly under mild conditions, providing good yields of the desired indole dioximes. The structures of synthesized vic‐dioximes were characterized using NMR, FT‐IR, and LC–MS. To shed light on the molecular structure, an extensive series of theoretical computations were performed on a representative molecule (3 a) using the DFT−B3LYP/6‐311++G(d,p) level of theory. The symmetrical and unsymmetrical indole dioximes obtained as key intermediates in this work have the potential to serve as essential building blocks for the design of new nortopsentin analogs with enhanced biological activities. To support this assumption, a representative molecule (3 a) was converted to a novel nortopsentin analog (4 a) having a 1,2,5‐oxadiazole (furazan) ring core.