naphthalene-2,3-diol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: bis-phenols such as 2,2-bis(p-hydroxyphenyl)propane and bis-(p-hydroxyphenyl)methane

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 5.0 g of 2,3-Dihydroxynaphthalene dimesitylate in 50 ml of acetic anhydride was treated with 12 ml of 70% HNO3 at such a rate as to keep the temperature between 37-40° C. A cooling bath should be kept under the flask, ready to be raised if necessary, as the temperature should not be allowed to exceed 45° C. The 12.0 ml of nitric acid was added to the reaction mixture over a period of 1-2 h. After 2 h, the reaction mixture was cooled to 5° C. in an ice bath and the precipitate was collected by filtration and washed with ether. Yield 5-Nitro-2,3-dihydroxynaphthalene dimesitylate 70%; mp 199-201° C., 1H NMR (DMSO-d6) δ 3.58 (s, 6H), 7.76 (t, J=8.0 Hz, 1H), 8.25-8.65 (m, 4H) between 37-40° C A cooling bath should be kept under the flask ready to be raised if necessary, as the temperature should not to exceed 45° C the precipitate was collected by filtration washed with ether

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

Procedure: As a demonstrative example, a cocrystal comprising a neutral API is described in this example. Cocrystals of nabumetone (a neutral API) and 2,3-naphthalenediol were prepared as follows. A 4.01 g sample of 2,3-naphthalenediol and 5.7 g of nabumetone were dissolved in 50 mL of nitromethane with heating. A solid was formed as the solution cooled and was allowed to stand overnight. The solid was filtered from the remaining solvent and dried in the air to yield 6.61 g (68%) of nabumetone:2,3-naphthalenediol (1:1) cocrystal. with heating A solid was formed as the solution cooled The solid was filtered from the remaining solvent dried in the air

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

Procedure: As a demonstrative example, a cocrystal comprising a neutral API is described in this example. Cocrystals of nabumetone (a neutral API) and 2,3-naphthalenediol were prepared as follows. A 4.01 g sample of 2,3-naphthalenediol and 5.7 g of nabumetone were dissolved in 50 mL of nitromethane with heating. A solid was formed as the solution cooled and was allowed to stand overnight. The solid was filtered from the remaining solvent and dried in the air to yield 6.61 g (68%) of nabumetone:2,3-naphthalenediol (1:1) cocrystal. with heating A solid was formed as the solution cooled The solid was filtered from the remaining solvent dried in the air

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

Procedure: Alternatively, the 2,3-trans-1,2,3,4-tetrahydro-5-[2-hydroxy-3-(substituted-amino)propoxy]-2,3-naphthalenediol isomer XXVII can be prepared from a 5,8-dihydro-1-naphthol of the structure ##STR34## prepared as described hereinbefore, by mixing a cooled solution (temperature less than about 30° C.) of 5,8-dihydro-1-naphthol in ethyl acetate with m-chloroperbenzoic acid and mixing the resulting slurry with a mixture of ethyl ether and aqueous sodium bicarbonate, to form 5,6,7,8-tetrahydro-6,7-epoxy-1-naphthol ##STR35## and reacting the 5,6,7,8-tetrahydro-6,7-epoxy-1-naphthol in tetrahydrofuran with aqueous perchloric acid at a temperature within the range of from about 0° to about 60° C., to form trans-5,6,7,8-tetrahydro-1,6,7-naphthalenetriol XXV which can be converted to the 2,3-trans-1,2,3,4-tetrahydro-5-[2,3-(epoxy)-propoxy]-2,3-naphthalenediol XXVI which in turn can be converted to the 2,3-trans-1,2,3,4-tetrahydro-5-[2-hydroxy-3-substituted amino)propoxy]-2,3-naphthalenediol XXVII in a manner similar to that described hereinbefore. prepared mixing the resulting slurry

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

Procedure: Alternatively, the 2,3-trans-1,2,3,4-tetrahydro-5-[2-hydroxy-3-(substituted-amino)propoxy]-2,3-naphthalenediol isomer XXVII can be prepared from a 5,8-dihydro-1-naphthol of the structure ##STR34## prepared as described hereinbefore, by mixing a cooled solution (temperature less than about 30° C.) of 5,8-dihydro-1-naphthol in ethyl acetate with m-chloroperbenzoic acid and mixing the resulting slurry with a mixture of ethyl ether and aqueous sodium bicarbonate, to form 5,6,7,8-tetrahydro-6,7-epoxy-1-naphthol ##STR35## and reacting the 5,6,7,8-tetrahydro-6,7-epoxy-1-naphthol in tetrahydrofuran with aqueous perchloric acid at a temperature within the range of from about 0° to about 60° C., to form trans-5,6,7,8-tetrahydro-1,6,7-naphthalenetriol XXV which can be converted to the 2,3-trans-1,2,3,4-tetrahydro-5-[2,3-(epoxy)-propoxy]-2,3-naphthalenediol XXVI which in turn can be converted to the 2,3-trans-1,2,3,4-tetrahydro-5-[2-hydroxy-3-substituted amino)propoxy]-2,3-naphthalenediol XXVII in a manner similar to that described hereinbefore. prepared mixing the resulting slurry

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

Procedure: Dimethylsulfate (32 ml) was added to the solution of 2,3-dihydroxynaphthalene (32 g) and sodium hydroxide (10 M, 32 ml) in water (300 ml). After being stirred for six hours at room temperature, the side product 2,3-dimethoxynaphthalene was filtered off (yield 16.6 g). The water phase was acidified, stirred on ice bath, filtered, washed with water and recrystallized from ethanol-water (3:2). Yield: 13.5 g, melting point 108-109° C. the side product 2,3-dimethoxynaphthalene was filtered off (yield 16.6 g) stirred on ice bath filtered washed with water recrystallized from ethanol-water (3:2)

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

Procedure: Acetylchloride (0.71 ml) was added to a solution of 2,3-dihydroxynaphthalene (1.6 g) and pyridine (0.81 ml) in ethyl acetate (20 ml) at 0° C. The mixture was stirred for few hours at room temperature and then washed with water, dried and evaporated to dryness. The crude product was recrystallized from ether. Yield: 0.52 g. washed with water dried evaporated to dryness The crude product was recrystallized from ether

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

Procedure: Phosphorous oxychloride (1.9 ml) was added to a solution of 2,3-dihydroxynaphthalene (3.2 g) in DMF (26 ml) at 0° C. The reaction mixture was kept for four hours at 100° C. Water (50 ml) was added to the cooled mixture and the resulting oily suspension refluxed for 20 min. The cool reaction mixture was poured into ice, filtered, washed with water and recrystallized from 2-propanol-water. Yield: 0.1 g, melting point 129-134° C. the resulting oily suspension refluxed for 20 min The cool reaction mixture was poured into ice filtered washed with water recrystallized from 2-propanol-water