Ultrasound-assisted reaction of 1,4-naphthoquinone with anilines through an EDA complex

Abstract

Naphthoquinone amino derivatives exhibit interesting physicochemical properties and a wide range of biological activities with potential medicinal applications. A clean, fast and simple method for the preparation of phenylamino-1,4-naphthoquinones is presented by the reaction of naphthoquinone (NQ) and anilines under ultrasound irradiation (US). Anilino derivatives were synthesized in good yields and shorter reaction times in comparison with the conventional method. This ultrasound procedure can be applied to the preparation of naphthoquinone derivatives with anilines containing electron-donor substituents (2-OMe, 4-OMe, 4-Me and 4-OEt) or halogen or electron-withdrawing substituents (4-F, 4-Cl, 4-Br, 3-F, 3-Cl, 3-Br, 4-Ac). This procedure was also applied to the reaction of anilines with 2,3-dichloro-1,4-naphthoquinone (DCNQ). A reaction mechanism involving an EDA complex is proposed based on NMR experiments and previous studies about solid/solid reactions.

Blue Light Irradiated Metal-, Oxidant-, and Base-Free Cross-Dehydrogenative Coupling of C(sp2)–H and N–H Bonds: Amination of Naphthoquinones with Amines

“…Orange solid, mp: 158–160 °C (literature 156–158 °C) . Yield 411 mg (87% at 1.26 mmol scale, reaction time: 2.5 h) using hexane/EtOAc (90:10) as eluent.…”

“…Three major synthetic strategies have been used for synthesizing 2-amino-1,4-naphthoquinone until now, one of which involves the nucleophilic displacement of the halo group in quinone with amines, ,,, while the second involves a direct 1,4-addition of amines to the quinones, ,, and the third strategy utilized metal catalyzed C–H functionalization of 1,4-naphthoquinone with an amine. ,,, However, the developed methodologies require strong acidic conditions, high temperature, metal catalysts, stoichiometric quantities of oxidant, or a strenuous process and also provide lower yields (Scheme ). ,,,− …”

The Relevance and Insights on 1,4-Naphthoquinones as Antimicrobial and Antitumoral Molecules: A Systematic Review

“…With a Lewis acid catalyst with strong oxidation properties such as CeCl3 (b), the reaction takes place in four hours, and high yields of products are obtained (60-90%). Performing the reaction under an alternative source of energy (c), e.g., microwave (MW) and ultrasound (US), results in higher yields (70-95%) of cleaner compounds within minutes (15-50 min) of reaction (Figure 3) [10,[37][38][39][40]. Leyva et al, 2017, synthesized anilino (PAN: phenylamino naphthoquinone) and dianilino derivatives.…”

Discovery of Anilino-1,4-naphthoquinones as Potent EGFR Tyrosine Kinase Inhibitors: Synthesis, Biological Evaluation, and Comprehensive Molecular Modeling

“…A mixture of 1,4-naphthoquinone 1 (2.4 mmol) and the appropriate aniline derivative 2 (2.0 mmol) in absolute 2-((4-Bromophenyl)amino)-3-chloronaphthalene-1,4dione (5). 65 From 2,3-dichloro-1,4-naphthoquinone (1a) and 4-bromoaniline (2d). Red wine solid.…”