An efficient synthesis of acridine-aza-anthraquinone hybrid compounds under microwave irradiation

The efficient synthesis of 12-substituted-3,4,4a,5,12,12a-hexahydrobenzo[b]acridine-1,6,11(2H)-triones starting from 2-amino-1,4-naphthoquinone, 1,3-cyclohexanedione, and different (hetero)aromatic aldehydes was developed. These reactions were carried out in acetic acid under microwave irradiation in the presence of p-toluenesulfonic acid as catalyst. The structure of the newly synthesized compounds were confirmed employing spectroscopic data as well as elemental analysis. The plausible mechanism of these three-component domino reactions was also described.
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An efficient synthesis of acridine-aza-anthraquinone hybrid compounds under microwave irradiationCite this paper: Vietnam J. Chem., 2023, 61(2), 262-268 Research articleDOI: 10.1002/vjch.202200164An efficient synthesis of acridine-aza-anthraquinone hybrid compounds under microwave irradiation Dang Thi Tuyet Anh1,2, Le Nhat Thuy Giang1,2*, Nguyen Van Tuyen1,2, Nguyen Thi Quynh Giang1,2, Nguyen Ha Thanh1,2** 1 Institute of Chemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi 10000, Viet Nam 2 Graduate University of Science and Technology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi 10000, Viet Nam Submitted August 29, 2022; Received September 29, 2022; Accepted November 8, 2022Abstract The efficient synthesis of 12-substituted-3,4,4a,5,12,12a-hexahydrobenzo[b]acridine-1,6,11(2H)-triones startingfrom 2-amino-1,4-naphthoquinone, 1,3-cyclohexanedione, and different (hetero)aromatic aldehydes was developed.These reactions were carried out in acetic acid under microwave irradiation in the presence of p-toluenesulfonic acid ascatalyst. The structure of the newly synthesized compounds were confirmed employing spectroscopic data as well aselemental analysis. The plausible mechanism of these three-component domino reactions was also described. Keywords. 2-Amino-1,4-naphthoquinone, benzo[b]acridine, multicomponent domino reaction.1. INTRODUCTION well as cytotoxic effect.[6] Clestophiline, marcanine A, and pixantrone (figure 1) are representatives ofThe nitrogen heterocyclic compounds have attracted this class of compounds.the interest of scientists due to their remarkably On the other hand, acridine and its derivativesbiological properties. Aza-anthraquinones, one of constitute well-known classes of bioactivethe most abundant chemical classes of natural and compounds with biological properties, includingsynthesized nitrogen-containing heterocycles, which antitumor,[7,8] antibacterial,[9] and antileukemichave known as intercalating DNA binding agents in activities.[10] Several benzoacridine derivatives cancancer chemotherapy due to the planar structure.[1,2] be proved as tubulin polymerization inhibitiors.[11]Besides that, aza-anthraquinone derivatives have Aminacrine, euflavine, porflavine (figure 1) havealso exhibited significant antibiotic[3], already approved as antibacterial drugs and haveantimicrobial , anti-inflammatory activities[5] as [4] been available in the market for many years.[12] Figure 1: Some bioactive aza-anthraquinone and acridine derivatives262 Wiley Online Library © 2023 Vietnam Academy of Science and Technology, Hanoi & Wiley-VCH GmbH 25728288, 2023, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/vjch.202200164 by Readcube (Labtiva Inc.), Wiley Online Library on [02/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons LicenseVietnam Journal of Chemistry Le Nhat Thuy Giang et al. Although heterocycles having aza-anthraquinone the reaction mixture. The resulting mixture wasand benzoacridine moieties are a great of interest, extracted with dichloromethane (3×20 mL), washedthe hybridization of these two scaffolds into one with brine (3×10 mL), dried over Na2SO4,single molecules have rarely been studied.[13,14] In concentrated, and purified by columnthat respect, in our ongoing program for the chromatography using a CH2Cl2/EtOAc (95:5 v/v) todevelopment of novel bioactive agents based on yield pure compounds 4a-k.nitrogen-containing heterocycles, herein we reportedan efficient synthesis of novel 12-substituted- 12-Phenyl-3,4,4a,5,12,12a-hexahydro3,4,4a,5,12,12a-hexahydrobenzo[b]acridine- benzo[b]acridine-1,6,11(2H)-trione (4a). Reaction1,6,11(2H)-triones derivatives 4a-k via microwave- time 20 min. Yield 91 mg (76 %), purple solid, mp.assisted three-component reactions starting from 2- 307-308 °C. IR (KBr) 3334, 3069, 3032, 2936,amino-naphthoquinone, 1,3-cyclohexanedione and 1668, 1637, 1590, 1484, 1386, 1346, 1303, 1230,various (hetero)aromatic aldehydes. 1202, 1159, 1132, 998, 942, 773 cm-1. 1H NMR (DMSO-d6, 500 MHz): δ 9.91 (1H, s, NH), 8.022. MATERIALS AND METHODS (1H, dd, J = 1.2 Hz, J = 7.8 Hz), 7.91 (1H, dd, J = 1.2 Hz, J = 7.8 Hz), 7.81 (1H, td, J = 7.2 Hz, J = 1.2 Hz), 7.77 (1H, td, J = 7.2 Hz, J = 1.2 Hz), 7.25 (2H,2.1. Method dd, J = 1.2 Hz, J = 7.8 Hz), 7.20 (2H, t, J = 7.8 Hz), 7.09 (1H, t, J = 7.2 Hz), 5.24 (1H, s, CH), 2.86 (dt, JReactions were performed in an Anton Paar ...