naphthalene-1,2-dione

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Benzo(A)phenazine was prepared with 1,2-phenylenediamine and 1,2-naphthoquinone, using standard condensation conditions. condensation conditions

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The process shown in Scheme 2 can be used for the preparation of compounds in Formula II, III and IV when R7 is not hydrogen and X is oxygen from same starting material 1-1 as shown in Scheme 1. The reaction of 2-hydroxy-1,4-naphthoquinone 1-1 with the appropriate allylbromide gives 2-allyloxy-1,4-naphthoquinone 2-2. Rearrangement of 2-2 in ethanol afford 2-hydroxy-3-allyl-1,4-naphthoquinone 2-3, which can be cyclized by sulfuric acid treatment to form orthonaphthoquinone 2-4. Oxidation of 2-4 with n-bromosuccinimide and lead tetraacetate gives 3-acetoxy-orthonaphthoquinone 2-5. Hydrochloric acid treatment of compound 2-5 gives 2-alkyl (or aryl)-3-alkyl (or aryl)-naphtha[2,3-b]furan-4,9-dione 2-6.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In order to test and evaluate the equipment and methods of the present invention, pre-coated 10 cm×10 cm HPTLC plates (Whatman) and test compounds α-ionone, phenanthrenequinone and 1,2-naphthaquinone (Aldrich) were obtained. The test compounds were initially diluted with acetone to about 10 mg/ml and stock solutions stored below 4° C. The stock solutions were further diluted with acetone just before use. Ceric sulfate prepared by adding 42 g of (NH4)4Ce(SO4)4 and 56 ml of conc. H2SO4 in 1 liter of distilled water was the chromogenic reagent.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In order to test and evaluate the equipment and methods of the present invention, pre-coated 10 cm×10 cm HPTLC plates (Whatman) and test compounds α-ionone, phenanthrenequinone and 1,2-naphthaquinone (Aldrich) were obtained. The test compounds were initially diluted with acetone to about 10 mg/ml and stock solutions stored below 4° C. The stock solutions were further diluted with acetone just before use. Ceric sulfate prepared by adding 42 g of (NH4)4Ce(SO4)4 and 56 ml of conc. H2SO4 in 1 liter of distilled water was the chromogenic reagent.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1,2-naphthoquinone (commercially available, 2.0 g) and 2,3-diamino-benzoic acid, diacetate salt, (3.79 g) was heated to reflux in acetic acid (30 mL) for 2 hours. The reaction mixture was cooled and the solvent removed in vacuo to yield a gum. This was purified using flash chromatography to yield a 2:1 mixture of the desired title compound to the undesired benzo[a]phenazine-8-carboxylic acid (840 mg). The two isomers were separated after further modification (see Reference Example 3B below). was heated The reaction mixture was cooled the solvent removed in vacuo to yield a gum This was purified to yield

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl 5-oxo-5,6,7,8-tetrahydro-1-naphthoate was prepared according to the literature (J. Org. Chem. 1976, p2918) from 2-methyl-2,6,7,8-tetrahydro-chromen-5-one (Tetrahedron Letters, 1975, p3407). Treatment of methyl 5-oxo-5,6,7,8-tetrahydro-1-naphthoate with selenium dioxide as described in Reference Example 1A yielded the corresponding 1,2-naphthoquinone, 5,6-dioxo-5,6-dihydro-naphthalene-1-carboxylic acid methyl ester, which was coupled with 2,3-diamino-benzoic acid, diacetate salt, as described in Reference Example 1A to yield the title compound.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Benzo(A)phenazine was prepared with 1,2-phenylenediamine and 1,2-naphthoquinone, using standard condensation conditions. condensation conditions

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of naphthalene-1,2-dione (0.103 g, 0.65 mmol) in acetonitrile (4.0 mL) was added 1-{[tert-butyl(diphenyl)silyl]oxy}-3-mercaptopropan-2-ol (0.226 g, 0.065 mmol) followed by diisopropylethylamine (0.114 mL, 0.065 mmol). The reaction mixture was stirred for 10 minutes at room temperature followed by addition of ethyl acetate (10 mL). The organic layer was washed with water (10 mL) and 1.0 N HCl (5 mL). The organic layer was dried with sodium sulfate and concentrated under reduced pressure. (ii) To the residue was added p-toluenesulfonic acid (0.48 g, mmol) followed by acetonitrile (5 mL). The reaction mixture was stirred at room temperature for 2 hours. To the reaction mixture was added ethyl acetate (10 mL) and the organic layer was extracted with water (10 mL). The organic layer was dried with sodium sulfate and concentrated under reduced pressure. The crude mixture was purified by flash column chromatography (SiO2, 100% dichloromethane) to give the product as a purple solid (0.061 g, 18%). M.p.=205-210° C.; 400 MHz 1H NMR (CDCl3) δ: 8.4-8.1 (m, 1H), 7.75-7.5 (m, 6H), 7.49-7.3 (m, 7H), 4.65-4.58 (m, 1H), 4.1-3.93 (m, 2H), 3.2-3.05 (m, 2H), 1.08 (s, 9H); LCMS: 501 [M+H]. The organic layer was washed with water (10 mL) and 1.0 N HCl (5 mL) The organic layer was dried with sodium sulfate concentrated under reduced pressure (ii) To the residue was added p-toluenesulfonic acid (0.48 g, mmol) The reaction mixture was stirred at room temperature for 2 hours To the reaction mixture was added ethyl acetate (10 mL) the organic layer was extracted with water (10 mL) The organic layer was dried with sodium sulfate concentrated under reduced pressure The crude mixture was purified by flash column chromatography (SiO2, 100% dichloromethane)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of naphthalene-1,2-dione (1.5 g, 9.5 mmol) in acetonitrile (50 mL) was added 3-mercaptohexan-1-ol (1.6 g, 11.9 mmol) followed by the addition of diisopropylethylamine (1.65 mL, 9.5 mmol). The mixture was stirred at room temperature for 30 minutes. The solvent was removed under reduced pressure and the residue dissolved in ethyl acetate (50 mL). The organic layer was washed with water (30 mL), dried with sodium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in acetonitrile (35 mL) and reacted with p-toluenesulfonic acid (1.9 g). The reaction mixture was stirred at room temperature for 40 min and solvent removed under reduced pressure. Crude product was purified by flash column (5% EtOAc in hexane to 15% EtOAc in hexanes) to give product as purple solid (0.170 g). M.p.=74-75° C. (decomposition); 400 MHz 1H NMR (DMSO-d6) δ: 7.88 (d, J=7.2 Hz, 1H), 7.73 (m, 2H), 7.56 (m, 1H), 5.08 (m, 1H), 4.67 (m, 1H), 3.58 (m, 1H), 1.40-1.82 (m, 6H), 0.89 (brt, 3H); LCMS: 289 [M+H]. The solvent was removed under reduced pressure the residue dissolved in ethyl acetate (50 mL) The organic layer was washed with water (30 mL) dried with sodium sulfate concentrated under reduced pressure The resulting residue was dissolved in acetonitrile (35 mL) reacted with p-toluenesulfonic acid (1.9 g) The reaction mixture was stirred at room temperature for 40 min solvent removed under reduced pressure Crude product was purified by flash column (5% EtOAc in hexane to 15% EtOAc in hexanes)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of naphthalene-1,2-dione (1.5 g, 9.5 mmol) in acetonitrile (50 mL) was added 3-mercaptohexan-1-ol (1.6 g, 11.9 mmol) followed by the addition of diisopropylethylamine (1.65 mL, 9.5 mmol). The mixture was stirred at room temperature for 30 minutes. The solvent was removed under reduced pressure and the residue dissolved in ethyl acetate (50 mL). The organic layer was washed with water (30 mL), dried with sodium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in acetonitrile (35 mL) and reacted with p-toluenesulfonic acid (1.9 g). The reaction mixture was stirred at room temperature for 40 min and solvent removed under reduced pressure. Crude product was purified by flash column (5% EtOAc in hexane to 15% EtOAc in hexanes) to give product as purple solid (0.170 g). M.p.=74-75° C. (decomposition); 400 MHz 1H NMR (DMSO-d6) δ: 7.88 (d, J=7.2 Hz, 1H), 7.73 (m, 2H), 7.56 (m, 1H), 5.08 (m, 1H), 4.67 (m, 1H), 3.58 (m, 1H), 1.40-1.82 (m, 6H), 0.89 (brt, 3H); LCMS: 289 [M+H]. The solvent was removed under reduced pressure the residue dissolved in ethyl acetate (50 mL) The organic layer was washed with water (30 mL) dried with sodium sulfate concentrated under reduced pressure The resulting residue was dissolved in acetonitrile (35 mL) reacted with p-toluenesulfonic acid (1.9 g) The reaction mixture was stirred at room temperature for 40 min solvent removed under reduced pressure Crude product was purified by flash column (5% EtOAc in hexane to 15% EtOAc in hexanes)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Benzo(A)phenazine was prepared with 1,2-phenylenediamine and 1,2-naphthoquinone, using standard condensation conditions. condensation conditions

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Benzo(A)phenazine was prepared with 1,2-phenylenediamine and 1,2-naphthoquinone, using standard condensation conditions. condensation conditions