Microwave-assisted reaction of 2,3-dichloronaphthoquinone with aminopyridines

Abstract

Piridilaminonaftoquinonas foram preparadas a partir da reação de 2,3-dicloro-1,4-naftoquinona e aminopiridinas empregando irradiação de microondas. O uso de microondas diminuiu os tempos de reação e forneceu os melhores rendimentos em todos os casos. As substâncias preparadas foram avaliadas em células de câncer de mama (MCF-7).The synthesis of pyridylaminonaphthoquinones by microwave-assisted reaction of 2,3-dichloro-1,4-naphthoquinone with aminopyridines is described. The use of microwave irradiation diminished the reaction times and improved the yields substantially in all these reactions. The compounds were tested for their cytotoxic activities against MCF-7 breast cancer cell line.Keywords: 2,3-dichloronaphthoquinone, microwave irradiation, aminopyridines, cytotoxic activity IntroductionThe aminonaphthoquinone scaffold is part of the structure of numerous natural and synthetic products associated with cytotoxic, antibacterial, antimalarial, and antifungal activities.1 Furthermore, many heterocyclic aminoquinones have been reported to show antitumor activity. 2A classical route to obtain 2-amino-1,4-naphthoquinones is by reaction of 1,4-naphthoquinones with amines followed by air oxidation or by nucleophilic addition-elimination on 2-halo-1,4-naphthoquinones.3,4 However, the generality of the methods is limited and most of them require long reaction times. In our continuous effort towards the synthesis of heterocyclic quinones with useful biological activities, 5 we were interested in the preparation of 2-pyridylamino-3-chloro-1,4-naphthoquinones because their potential as antitumor agents was unexplored. Calandra and Adams, 6 and Truit and co-workers. 7 have reported that reaction of 2,3-dichloro-1,4-naphthoquinone (1) with 2-aminopyridine (2) under reflux of ethanol gives 2-(2-pyridylamino)-3-chloro-1,4-naphthoquinone (3), which affords 1,4-naphthoquinone derivative 4 upon treatment with acetic acid. However, Mosby and Boyle found that the reaction of 1 and 2 under reflux of ethanol in the presence of sodium bicarbonate leads to 1,2-naphthoquinone derivative 5 (46%) and not to 2-pyridylamino-1,4-naphthoquinone 3 neither p-quinone 4 (Scheme 1). 8Considering the importance of the pyridylamino-1,4-naphthoquinone moiety as pharmacophoric scaffold, we became interested in the application of microwave irradiation to study the reaction of 2,3-dichloro-1,4-naphthoquinone (1) with different aminopyridines. It is noteworthy that microwave techniques have been demonstrated as a valuable tool in accelerating the rate and yield of organic reactions in general. 9 Results and DiscussionWe first performed the reaction of dichloronaphthoquinone 1 with 2-aminopyridine (2) employing conventional heating. Thus, treatment of quinone 1 with one equivalent of 2 in refluxing ethanol for 15 hours gave o-quinone 5 in 45% yield. The melting point and 1 HNMR spectra of compound 5 were in agreement with literature values, 10 and thus Mosby and Boyle results were confirmed.8 The microwave-assisted condensation reaction of 1 and 2 in et...

Recent advances in 1,4-benzoquinone chemistry

“…13 Wide applications of quinones can also be found in the field of synthetic organic chemistry. [14][15][16][17][18][19][20] Coordination chemistry of quinones is also quite rich from the perspective of designing magnetic materials 21 and understanding photophysical properties. 22 The studies of quinonoid compounds have focused on a broad spectrum of topics viz occurrence in nature, 2 syntheses, 23 cycloaddition reactions, 24 photochemistry and pulse radiolysis, 1,25,26 computational chemistry, etc.…”

“…El-Feraly and co-workers 52 isolated five new alkylated benzoquinones (16)(17)(18)(19)(20) as methyl ether derivatives from a complex mixture of alkylated hydroxy benzoquinones obtained from the fruits of Maesa lanceolata.…”

Preparation and biological evaluation of novel acylhydrazide derivatives of 2,3-dichloronaphthoquinone

“…28 The reported activity of 2,3-dichloro-1,4-naphthoquinone 4 is comparable to the synthesized derivatives with IC 50 31 µM against MCF-7 tumor cell lines. 29 The activity of each compound varied between the two cell lines, indicating cell type specificity and suggesting different interactions with the cells. …”

Reactions of 5-oxo-1-phenylpyrrolidine-3-carbohydrazides with 1,4-naphthoquinone derivatives and the properties of the obtained products

“…Naphthoquinones and their various derivatives as a class display many types of biological activity. They are active against different strains of bacteria and fungi [1][2][3][4][5][6][7][8][9][10], show insecticidal [11,12], molluscicidal [13], and antiproliferative [4,14] properties, and are anticancer agents [15][16][17][18][19][20]. Furthermore, hydrazones have been demonstrated to possess many types of biological activity [21].…”

“…The assignment of resonances in the NMR spectra was based on the chemical shift theory, using previously determined [23] and published [24] increments of substituents, signal intensity arguments, and multiplicities, and a comparison with structurally related compounds [20,[25][26][27][28][29][30][31][32][33][34][35][36][37][38]. The DEPT ( 13 C) and 1 H/ 13 C 2D (HETCOR) methods were used in some cases.…”