Synthesis of some NH- and NH,S- substituted 1,4-quinones

A series of NH-substituted-1,4-quinones, possessing one, two, three or not chlorine, were synthesized by the reaction between different quinones (p-chloranil (1), p-toluquinone (2), or 2,3-dichloro-1,4-naphthoquinone (3)) and (-)-cis-myrtanylamine (5) via nucleophilic reactions. Moreover, 2-bromo-1,4-naphthoquinone (4) was reacted with 2-(methylthio)ethylamine (11) to produce amino-substituted naphthoquinones (12 and 13), bearing with bromine and not bromine. In addition, 2-bromo-1,4-naphthoquinone (4) was reacted with 4′-aminodibenzo-18-crown-6 (14) and 4′-aminobenzo-18-crown-6 (16) to yield crown-containing 1,4-naphthoquinones (15 and 17), respectively. New compounds were characterized, providing 1H NMR, 13C NMR, FTIR, MS-ESI, UV/Vis and elemental analysis.

The importance of this kind of compounds has motivated this study to synthesize 1,4-naphtho(benzo)quinones bearing with amino and/or thio. Thus, p-chloranil 1, methyl-p-benzoquinone 2, dichloro-1,4-naphthoquinone 3 and 2-bromo-1,4naphthoquinone 4 were used as lead molecules, as shown Figure. Various spectroscopic techniques (UV/Vis, FTIR, 1 H NMR, 13 C NMR, MS-ESI) have been employed to characterize the synthesized compounds. It is expected that the new synthesized compounds will be useful for pharmacological field with their potential biological activities.

Chemistry
All the chemicals used (1, 2, 3, 4, 5, 11, 14, 16, 18) were commercially purchased and used without further purification. To measure melting points, Buchi B-540 was used. The elemental analyses, IR spectra, and UV-Vis spectra were carried out by using the ThermoFinnigan Flash EA1112, Thermo Scientific Nicolet 6700, and Shimadzu UV/Vis spectrophotometer 2600 (in CHCl 3 ), respectively. The UV-Vis spectra were recorded on a Shimadzu UV/Vis spectrophotometer 2600, in CHCl 3 . The mass spectra were performed on a ThermoFinnigan LCQ AdvantageMAX system. 1 H and 13 C NMR spectra were performed in CDCl 3 solution on a spectrometer (Varian Unity Inova). Chemical shifts (δ, ppm) are reported by using tetramethylsilane as internal standard. Column chromatography was performed on glass columns by using silica gel (70-230 mesh).

Synthesis of Compound 15
The solution of 4 (63 mg, 0.27 mmol) and 4′-aminodibenzo-18-crown-6 14 (0.1 g, 0.27 mmol) with CH 3 COONa in CHCl 3 and ethanol was allowed to stir at room temperature by monitoring the progression the reaction mixture with TLC. Then, the reaction mixture was extracted with water and CHCl 3 . The organics were dried over sodium sulfate and removed under vacuo; thus, the crude mixture was obtained. The crude mixture was then purified by column chromatography on silica gel (stationary phase) with ethyl acetate/CH 2 Cl 2 (10/1) (mobil phase) to afford product 15: Yield: 69% (112 mg

Synthesis of compound 17
The solution of 2-bromo-1,4-naphthoquinone 4 (72 mg, 0.30 mmol) and 4′-aminobenzo-18-crown-6 16 (0.1 g, 0.30 mmol) with Na 2 CO 3 in CH 2 Cl 2 was allowed to stir at reflux temperature by monitoring the progression of the reaction mixture with TLC. Then, the reaction mixture was extracted with water and CHCl 3 . The organics were dried over sodium sulfate and removed under vacuo; thus, the crude mixture was obtained. The crude mixture was then purified by column chromatography on silica gel (stationary phase) with ethyl acetate/CH 2 Cl 2 (10/1) (mobil phase) to afford product 17: R f = 0.8 (CH 3

Synthesis of compound 19
The solution of 17 (40 mg, 0.07 mmol) and 1-dodecanethiol 18 (510 mg, 2.52 mmol) in CHCl 3 in the presence of triethylamine (2-3 mL) was allowed to stir at reflux temperature by monitoring the progression of the reaction mixture with TLC. Then, the reaction mixture was extracted with water and CHCl 3 . The organics were dried over sodium sulfate and removed under vacuo; thus, the crude mixture was obtained. The crude mixture was then purified by column chromatography on silica gel (stationary phase) with ethyl acetate/CH 2
The reaction of 4 with 11 yielded two new amino-substituted-1,4-naphthoquinones (12 and 13), including bromine and not bromine, respectively. In the 1 H-NMR spectrum of 13, a singlet appeared at 5.75 ppm, which was assignable to the proton presence of 13 instead of bromine. In addition, in the FTIR spectra of these derivatives (12 and 13) the characteristic bands observed at 1673 and 1664 cm -1 were assignable to the C=O stretching vibrations, respectively. Compound 17 was reacted with 1-dodecanethiol 18, in the presence of triethylamine, providing both of NH-and SRsubstituted-1,4-naphthoquinone 19, which including crown structure. In the proton NMR spectrum of 19, CH napht , CH arom , and CH 2crown exhibited signals in a lower field than in the starting compound 17, because of the bonding S-(CH 2 ) 11 -CH 3 to quinoid structure, instead of bromine.