Unexpected formation of pyridodiindole derivatives with cytotoxic activity via double nenitzescu reaction

Abstract

The title compounds 10 and 11 were prepared by a one‐step procedure from 1,4‐benzoquinone (4) and pyridine‐2,4,6‐triamine (5) via an extension of the Nenitzescu reaction

Nenitzescu Indole Synthesis: 1929-2019 Unexpected Formation of a Pyrrole-Azepine Hybrid in the Nenitzescu Indole Synthesis: A Reinvestigation

“…As a consequence, this name reaction was also extended to instances when nonindolic heterocyclic systems were obtained, particularly to benzofuran derivatives. The formation of compounds with unexpected structures has also been observed with benzoquinones and enamines under Nenitzescu reaction conditions [13,28,29]. From the Nenitzescu reaction between ethyl 3aminocinnamate and 1,4-benzoquinone in 1-butanol, Raileanu and Palaghita [28] isolated in 20% yield a yellow compound which was proposed as having the unexpected diazaheptalene structure 8 (see below) on the basis of elemental analysis, IR and NMR spectroscopy.…”

“…Even though the yields are low and only a few methods are known for obtaining 5-hydroxyindoles, the Nenitzescu reaction remains the method of choice due to its experimental simplicity, accessibility and the large variety of possible starting materials. The extension of the Nenitzescu reaction by varying the structure of the quinone and/or the enamine has also proved to be a fruitful synthetic procedure for compounds incorporating the 5hydroxyindole moiety, such as pyrido [2,3-b]indoles [13], benzocarbazoles [14,15], furo [3,2-h]indoles, furo [2,3-g]indoles [16], dihydrobenzo[g]indoles [17], benzo[g]isoquinoline [18], pyrrolo [2,3-h] quinolines [19], benzofuro [3,2-c]carbazol [20] and others.…”

Nenitzescu 5‐Hydroxyindole Synthesis

“…A summary of these reports is listed in Table 2 [26][27][28][29][30][31][32][33][34][35][36][37][38][39]. A summary of these reports is listed in Table 2 [26][27][28][29][30][31][32][33][34][35][36][37][38][39].…”