Amination of 5-hydroxy-1,4-naphthoquinone in the presence of copper acetate

Abstract

The reaction of 5-hydroxy-1,4-naphthoquinone with butylamine in the presence of copper(II) acetate monohydrate on heating resulted in the formation of a mixture of regioisomeric 2,6-and 2,8-bis(butylamino)-5-hydroxy-1,4-naphthoquinones.Naphthoquinone derivatives having hydroxy and amino groups attract interest as potential biologically active substances [1], dyes [2], and organic materials for nonlinear optics [3]. It is known that 5-hydroxy-1,4-naphthoquinone (I, juglone) reacts with amines only at the quinoid ring to give the corresponding 2-and 3-amino derivatives; no examples of introduction of the second amino group into the aromatic ring were reported [1,4].The present study was aimed at synthesizing alkylamino derivatives of juglone by its reaction with butylamine in the presence of copper(II) acetate. Castillo et al. [5] previously showed that the reaction of juglone with butylamine in a two-phase system CH 2 Cl 2 -H 2 O leads to formation of isomeric 2-and 3-butylamino derivatives II and III in 11 and 6% yield, respectively (Scheme 1). We found that the yield of compounds II and III may be raised to 15 and 11%, respectively, by carrying out the reaction in ethanol and that the amination of juglone complex with copper(II) acetate monohydrate Cu(OAc) 2 · H 2 O in ethanol gives a mixture of amines II and III in 57 and 10% yield, respectively. Increased selectivity of the reaction toward 2-butylamino derivative II may be rationalized by enhancement of the electron-withdrawing effect of the oxygen atom on C 4 due to coordination to copper(II) ion, as was observed in the amination of 5,8-quinolinequinone in the presence of metal salts [6].Unlike 3-butylamino derivative III, 2-butylamino-5-hydroxy-1,4-naphthoquinone (II) reacted with excess butylamine (used as solvent) in the presence of Cu(OAc) 2 · H 2 O to give two isomeric products IV and V in which the second alkylamino group is attached to the aromatic ring of naphthoquinone (Scheme 2). Bis-(butylamino) derivatives IV and V were not formed when the reaction was performed in butylamine as solvent in the absence of copper salt or in ethanol in the presence of Cu(OAc) 2 · H 2 O.Presumably, introduction of the second amino group into the aromatic ring in the presence of Cu(OAc) 2 · H 2 O is favored by formation of copper chelate for which a contribution of ana-quinoid structure may be assumed, as for chelates derived from α-hydroxy-and α-aminoanthraquinones [7] and naphthazarin [8]. It is known that naphthoquinones having hydroxy or amino groups in the peri positions with

Synthesis and Biological Evaluation of Lipophilic 1,4-Naphthoquinone Derivatives against Human Cancer Cell Lines

“…The reaction produced 13a in 13.9% as an orange red solid; mp 154.6–155.4 °C (lit. [41] 156–157 °C). 1 H-NMR (500 MHz, CDCl 3 ) δ H 0.96 (t, J = 7.4 Hz, 3H, CH 3 ), 1.43 (p, J = 7.5 Hz, 2H, H-2′), 1.67 (p, J = 7.5 Hz, 2H, H-3′), 3.17 (q, J = 6.9 Hz, 2H, H-1′), 5.61 (s, 1H, H-3), 6.04 (s, 1H, -NH), 7.22 (dd, J = 0.8, 8.3 Hz, 1H, H-8), 7.44 (t, J = 8.0 Hz, 1H, H-7), 7.56 (dd, 1H, J = 0.8, 7.6 Hz, H-6), 13.08 (s, 1H, 5-OH); 13 C-NMR (125 MHz, CDCl 3 ) δ C 13.90 (CH 3 ), 20.40 (C-2′), 30.43 (C-3′), 42.63 (C-1′), 99.81 (C-3), 115.19 (C-9), 119.25 (C-6), 126.18 (C-8), 130.70 (C-10), 134.05 (C-7), 148.90 (C-2), 161.33 (C-5), 181.41 (C=O), 189.14 (C=O); LC-MS (ESI + , m / z ) calculated for C 14 H 15 NO 3 : 245.11, found for 268.24 [M + Na] + ; HRMS-ESI: m / z calculated for C 14 H 16 O 3 N: 246.1125 [M + H] + , found for 246.1120.…”

Direct Functionalization of para‐Quinones: A Historical Review and New Perspectives

“…The reactivity of amine vs quinone was also studied, and it was observed that amines have relatively weak basicity compared to Lewis acid quinone, leading to the failure of the amination of quinones. Inspired by these results, Ektova and co‐workers explored the regioselectivity for amination of 5‐hydroxy‐1,4‐naphthoquinone, and they further studied the crystal packing of these molecules [120b] . From structural analysis, they found that extended π‐conjugation system with intramolecular charge transfer from the hydroxy and amino groups to the carbonyl groups and also substantial intra and intermolecular H‐bonding enhancing the stacked molecular bands, which could be responsible for their non‐linear optical properties.…”

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

“…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 ). ,,,− …”