Choline Hydroxide Promoted Synthesis of N‐Aryl Anthraquinone Derivatives: Metal Free Approach to Ullmann Coupling Reactions

Abstract

A simple metal free alternative procedure for Ullmann type C−N coupling reactions has been achieved by allowing substituted bromo/chloro anthraquinones to react with a variety of amines in the presence of Choline hydroxide (ChOH). This reaction is also extended towards synthesis of commercially available Acid Blue 25 dye. Good to excellent yields (78‐95%) of N‐aryl anthraquinone products were obtained under mild conditions in reduced reaction time. This reaction is driven by SNAr mechanistic pathway, moreover compared to conventional methods, no metal catalyst is required, ChOH is an environmentally benign, cheaper catalyst recyclable up to five runs without remarkable loss of activity.

1-Hydroxyanthraquinones Containing Aryl Substituents as Potent and Selective Anticancer Agents

“…Organic layer was dried over MgSO 4 , filtered and concentrated under reduced pressure. The residue was purified by column chromatography (benzene or CCl 4 /benzene, 1:1) to afford the corresponding compounds (13)(14)(15)(16)(17)(18)(19)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31).…”

“…9,10-Anthraquinones functionalized with amide-, alkylamino-, arylamino-and alkoxy-type groups have been successful obtained by reactions involving easily available 9,10-anthraquinones bearing amino [15,16] or hydroxy [17] groups, or anthraquinone derivatives bearing halogen atoms [18][19][20][21][22], or tosyloxy [23] reactive sites. For synthesis of amino substituted anthraquinones, which are increasingly widely used in practice, more and more attention has been drawn to the development of C-N coupling processes, for example, the copper(0)-catalyzed Ullmann-type reaction of bromo/chloro anthraquinones with a variety of amines [5,[24][25][26] or the Pd-catalyzed Buchwald-Hartwig cross coupling reaction [27,28]. Currently, the most successfully developed method of functionalization of the anthraquinone core represent the Pd-catalyzed C-C cross-coupling reaction of 9,10-anthraquinones bearing suitable leaving groups, including anthraquinoyl triflates and bistriflates [29][30][31][32][33], halides [34,35] or boronic acid pinacol ester of 9,10-anthraquinone [36,37].…”

“…Scheme 2. Synthesis of 4-substituted 1-hydroxyanthraquinones(24)(25)(26)(27)(28)(29)(30)(31). Reagents and conditions: (b)(1.2 equiv.…”

Synthesis, characterization and anticancer evaluation of nitrogen-substituted 1-(3-aminoprop-1-ynyl)-4-hydroxyanthraquinone derivatives

“…For synthesis of nitrogen substituted anthraquinones, besides to the routes for the construction of anthraquinone core (for example, of Friedel-Crafts condensations of benzene derivatives with functionalized phthalic anhydrides or phthaloyl dichlorides [23]), attention has been drawn to the development of C-N coupling processes, for example, the copper(0)-catalyzed Ullmann-type reaction of bromo/chloro anthraquinones with a variety of amines [24][25][26][27] or the Pd-catalyzed Buchwald-Hartwig cross-coupling reaction of halogen substituted anthraquinones [28,29].…”

Reshaping Ullmann Amine Synthesis in Deep Eutectic Solvents: A Mild Approach for Cu-Catalyzed C–N Coupling Reactions With No Additional Ligands

“…The latter was recovered and reused, jointly with the eutectic mixture, for five consecutive runs (Shaabani and Afshari, 2018). N -arylantraquinone derivatives have also been successfully synthesized, under metal-free conditions and in the presence of choline hydroxide as an environmentally benign and recyclable catalyst, however, via an S N Ar mechanistic pathway (Pant et al, 2018). Building on recent breakthroughs made by our research group (Mallardo et al, 2014; Sassone et al, 2015; Cicco et al, 2016, 2017, 2018; Mancuso et al, 2016; Dilauro et al, 2017, 2018, 2019; Messa et al, 2018; Ghinato et al, 2019) and others (Vidal et al, 2014, 2016; Sánchez-Condado et al, 2019) on the effectiveness of using non-conventional reaction media (e.g., DESs and water) for promoting metal-catalyzed and organolithium/Grignard reagent-mediated deprotonation and nucleophilic addition reactions to unsaturated organic substrates under aerobic conditions, here we report the CuI-catalyzed UAS in DESs.…”