Syntheses of 2-substituted 1-amino-4-bromoanthraquinones (bromaminic acid analogues) – precursors for dyes and drugs

Abstract

SummaryAnthraquinone (AQ) derivatives play a prominent role in medicine and also in textile industry. Bromaminic acid (1-amino-4-bromoanthraquinone-2-sulfonic acid) is an important precursor for obtaining dyes as well as biologically active compounds through the replacement of the C4-bromo substituent with different (ar)alkylamino residues. Here we report methods for the synthesis of bromaminic acid analogues bearing different substituents at the 2-position of the anthraquinone core. 1-Aminoanthraquinone was converted to its 2-hydroxymethyl-substituted derivative which, under different reaction conditions, yielded the corresponding carbaldehyde, carboxylic acid, and nitrile derivatives. The latter was further reacted to obtain 1-amino-2-tetrazolylanthraquinone. Subsequent bromination using bromine in DMF led to the corresponding bromaminic acid derivatives in excellent isolated yields (>90%) and high purities. Alternatively, 1-amino-4-bromo-2-hydroxymethylanthraquinone could be directly converted to the desired 2-substituted bromaminic acid analogues in high yields (85–100%). We additionally report the preparation of bromaminic acid sodium salt and 1-amino-2,4-dibromoanthraquinone directly from 1-aminoanthraquinone in excellent yields (94–100%) and high purities. The synthesized brominated AQs are valuable precursors for the preparation of AQ drugs and dyes.

Anthraquinones As Pharmacological Tools and Drugs

“…Biologically active anthraquinone derivatives have also been identified in bacteria, fungi, and insects . Both natural and synthetic anthraquinones are widely used in textile dying, paints, imaging devices, foods, cosmetics, and pharmaceuticals . Moreover, they serve as catalysts in many chemical and biogeochemical processes, such as reductive degradation of contaminants, based on their redox potential …”

“…12 Both natural and synthetic anthraquinones are widely used in textile dying, paints, imaging devices, foods, cosmetics, and pharmaceuticals. [13][14][15][16][17][18][19][20][21][22] Moreover, they serve as catalysts in many chemical and biogeochemical processes, such as reductive degradation of contaminants, based on their redox potential. 23,24…”

Synthesis and In Silico Study of 4-Substituted 1-Aminoanthraquinones

“…2) which is the basic starting material for the preparation of biologically active anthraquinone derivatives and numerous dyes [4][5][6]. In fact, bromaminic acid and its salts are widely used as intermediate products for the synthesis of anthraquinone derivatives, including acid dyes, via substitution of the 4-bromine atom by (aryl)alkylamino group [7][8][9]. iii: phosphate buffer, pH 6-7, Cu(0), microwave irradiation, 100-120°C, 5-24 min.…”

Synthesis of Anthraquinones by Iridium-Catalyzed [2 + 2 + 2] Cycloaddition of a 1,2-Bis(propiolyl)benzene Derivative with Alkynes

“…Anthraquinones and their derivatives are important structures found in natural products and bioactive compounds and show a broad range of bioactivities including anti-tumor [1,2], cytotoxic [3], anti-cancer [4][5][6], anti-bacterial [7,8], laxative [9], anti-arthritic [10], anti-fungal [11], anti-platelet [12,13], and neuroprotective effects [14]. Moreover, anthraquinones have been widely used as catalysts for producing hydrogen peroxide [15], dyes for fibers [16,17] and cells [18], a digestion catalyst for wood [19], and chemical sensors [20]. Thus, the development of synthetic methods for the formation of multi-substituted anthraquinones is an important research topic, and several synthtic methods including the oxidation of anthracene [21,22], the Friedel-Crafts reaction of phthalic anhydride [23], and the Diels-Alder reaction of naphthoquinones followed by aromatization [24] have been developed.…”