“Anti-Michael” and Michael Additions in the Reactions of 2-Arylmethyliden-1,3-Indandiones with 2-Aminothiophenol

Abstract

A novel 2-indano[2,3b]-2-ferrocenyl-and 2-indano[2,3b]-2-(p-methoxyphenyl) [1,5]benzo-2,5-dihydrothiazepine 5a,b (addition Michael/cyclization) (~30.32%), indano[2,3b]-2-ferrocenyl-and 2-(p-methoxyphenyl) [1,4] benzothiazine 4a,b (addition "anti-Michael"/cyclization) (~45.43%), respectively, were obtained by the condensation of 2-ferrocenyl-and 2-(p-methoxyphenyl)methyliden-1,3-indandiones 1a,b with o-aminothiophenol 2 in the presence of AcOH and HCl. A new "anti-Michael" addition reaction of 1,4-bis-heteronucleophile 2 into 2-arylmethyliden-1,3-indandiones was reported.As a result of this reaction the product 1a,b was obtained. The structures of the resultant compounds were elucidated by IR, 1 H and 13 C NMR spectroscopy, mass spectrometry, elemental and X-ray diffraction analysis. The in vitro antitumor activity of the obtained products was researched using the following human cancer cell lines: glioblastoma (CNS U-251), prostatic adenocarcinoma (PC-3), chronic myelogenous leukemia (K562), colorectal adenocarcinoma (HCT-15), mammary adenocarcinoma (MCF-7), and small cell lung cancer (SKLU) and the sulforhodamine B (SRB) method. Among these new compounds some thiazine and thiazepine derivatives showed compelling in vitro antitumor effects on cell lines K-562, HCT-15, SKLU-1 and MCF-7.

Synthesis of two quinolines from one substrate: The beginning of regulating the duality of free radicals

“…To achieve this objective, we envisioned the development of distinct synthetic protocols to regulate the electrophilic-nucleophilic bias of free radicals for the synthesis of multiply substituted quinolines in a productive fashion. Further, we wanted to extend the addition reactions of α, β-unsaturated ketones, namely Michael addition and anti-Michael addition [59][60][61] , to involve free radicals as substrates. In this regard, the imine C-H bond of (E)-3-(2-(((E)-benzylidene)amino)phenyl)acrylate was photoactivated to obtain the imine carbon radical.…”

Synthesis of Substituted Benzothiazepine Compounds with Medicinal Potential

“…[1]. During the course of our investigations, five articles [2] [3] [4] [5] [6] and three patents [7] [8] [9] were published that build upon the original report of this compound series by Krysin [1]. The majority of analogs described include structural variation of the benzaldehyde-derived aromatic ring, in part due to the ready commercial availability of structurally varied starting materials [2]- [9].…”

“…The majority of analogs described include structural variation of the benzaldehyde-derived aromatic ring, in part due to the ready commercial availability of structurally varied starting materials [2]- [9]. Preparation of analogs resulting from structural variation of the indanedione-derived aromatic ring is far fewer [4], likely because the requisite substituted indanedione starting materials are not commercially available but rather must be prepared according to literature precedent [10] [11] [12]. Just three analogs are described displaying structural variation of the 2-aminothiol-derived aromatic ring [2] [5] [8].…”