4-methyl-1,2-dihydronaphthalene

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

Procedure: α-Tetralone was reacted with methylmagnesium iodide as described in J. Org. Chem., 26, 4165 (1961), without isolation of the intermediate 1-methyl-1-tetralol, to give the desired product, after distillation, in 68% yield as a colorless oil, boiling point 55-57° C. at 0.8 mm Hg.

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

Procedure: Following the procedure of Example 1, step 3, 5.00 g (34.7 mmol) of 1-methyl-3,4-dihydronaphthalene in 35 ml of acetic acid was reacted with 11.3 ml of 37% formaldehyde solution and 14.96 g of 2-adamantanamine hydrochloride. Work up gave 14.47 g of crude 3-(2-adamantyl)-1,2,3,4,4a,5,6,10b-octahydrobenz[f]isoquinoline. Following the procedure of Example 2, this was reacted with 2.09 g of lithium wire in 500 ml of liquid ammonia, 200 ml of anhydrous THF and 5 ml of aniline. Chromatography on flash silica, eluting with 2-10% methanol/dichloromethane, then on alumina, eluting with 0-4% ethyl acetate/petroleum ether, gave 2.73 g (24%) of the title product as a white solid. The hydrochloride salt was made using ethereal hydrogen chloride. Upon evaporation of the solvent and recrystallisation from ethanol/ethyl acetate/petroleum ether, the title product hydrochloride was obtained as a white solid, m.p. 247°-252° C. NMR δ(D2O/CD3CN) 1.52 (1H, m), 1.69-1.98 (15H, m), 2.48 (2H, s), 2.59-2.75 (3H, m), 2.91-3.09 (3H, m), 3.29-3.34 (1H, m), 3.79 (1H, m), 3.95 (1H, m), 7.18-7.24 (3H, m), 7.30-7.33 (1H, m). m/z (CI+, NH3) 322 (M+H)+.

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

Procedure: Following the procedure of Example 1, step 3, 5.00 g (34.7 mmol) of 1-methyl-3,4-dihydronaphthalene in 35 ml of acetic acid was reacted with 11.3 ml of 37% formaldehyde solution and 14.96 g of 2-adamantanamine hydrochloride. Work up gave 14.47 g of crude 3-(2-adamantyl)-1,2,3,4,4a,5,6,10b-octahydrobenz[f]isoquinoline. Following the procedure of Example 2, this was reacted with 2.09 g of lithium wire in 500 ml of liquid ammonia, 200 ml of anhydrous THF and 5 ml of aniline. Chromatography on flash silica, eluting with 2-10% methanol/dichloromethane, then on alumina, eluting with 0-4% ethyl acetate/petroleum ether, gave 2.73 g (24%) of the title product as a white solid. The hydrochloride salt was made using ethereal hydrogen chloride. Upon evaporation of the solvent and recrystallisation from ethanol/ethyl acetate/petroleum ether, the title product hydrochloride was obtained as a white solid, m.p. 247°-252° C. NMR δ(D2O/CD3CN) 1.52 (1H, m), 1.69-1.98 (15H, m), 2.48 (2H, s), 2.59-2.75 (3H, m), 2.91-3.09 (3H, m), 3.29-3.34 (1H, m), 3.79 (1H, m), 3.95 (1H, m), 7.18-7.24 (3H, m), 7.30-7.33 (1H, m). m/z (CI+, NH3) 322 (M+H)+.

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

Procedure: Following the procedure of Example 1, step 3, 2.05 g (14.0 mmol) of 1-methyl-3,4-dihydronaphthalene in 14 ml of acetic acid was reacted with 4.54 ml of 37% formaldehyde solution and 6.03 g of 1-adamantanamine hydrochloride. Work up gave 5.58 g of crude 3-(1-adamantyl)-1,2,3,4,5,6-hexahydrobenz[f]isoquinoline. Following the procedure of Example 2, this was reacted with 1.02 g of lithium wire in 400 ml of liquid ammonia, 100 ml of anhydrous THF and 2 ml of aniline. Chromatography on flash silica, eluting with 5-20% methanol/dichloromethane, then on alumina, eluting with 2-7% ethyl acetate/petroleum ether, afforded 0.54 g (12%) of the title product as a white solid. The hydrochloride salt was made using ethereal hydrogen chloride. Upon evaporation of the solvent and recrystallisation from methanol/petroleum ether, the title product hydrochloride was obtained as a white solid, m.p. 252°-255° C. NMR δ(D2O, CD3CN) 1.56 (1H, m), 1.68-1.92 (9H, m), 2.02-2.04 (6H, m), 2.27 (3H, s), 2.61 (1H, m), 2.74 (1H, d of d), 2.82 (1H, t, J=12.0 Hz), 2.92-2.95 (2H, m), 3.08 (1H, t of d), 3.65 (1H, m), 3.82 (1H, m), 7.19-7.23 (3H, m), 7.29-7.30 (1H, m). m/z (CI+, NH3) 322 (M+H)+, 195. Analysis calcd. for C23H32ClN: C, 77.17; H, 9.01; N, 3.91%. Found: C, 77.09; H, 8.95; N, 3.89%.

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

Procedure: Following the procedure of Example 1, step 3, 1.04 g (7.19 mmol) of 1-methyl-3,4-dihydronaphthalene in 7 ml of acetic acid was reacted with 2.33 ml of 37% formaldehyde solution and 1.58 g of propylamine hydrochloride. Work up gave 1.98 g of crude 1,2,3,4,5,6-hexahydro-3-propyl-benz[f]isoquinoline. Following the procedure of Example 2, this was reacted with 0.435 g of lithium wire in 250 ml of liquid ammonia, 40 ml of anhydrous THF and 1 ml of aniline. Chromatography on flash silica, eluting with 5-10% methanol/dichloromethane, then on alumina, eluting with 2-5% ethyl acetate/petroleum ether, gave 0.497 g (30%) of the title product as a colourless oil. The hydrochloride salt was made using ethereal hydrogen chloride. Upon evaporation of the solvent, the title product hydrochloride was obtained as a white solid, m.p. 257°-259° C. (dec). NMR δ(D2O) 1.00 (3H, t, J=7.4 Hz), 1.57 (1H, m), 1.68-1.92 (5H, m), 2.66-2.76 (2H, m), 2.87-2.95 (3H, m), 3.12-3.16 (3H, m), 3.63 (1H, m), 3.77 (1H, m), 7.22-7.31 (3H, m), 7.35-7.38 (1H, m). m/z (CI+, NH3) 230 (M+H)+, 200 (M-CH2CH3)+. Analysis calcd. for C16H24ClN: C, 72.29; H, 9.10; N, 5.27%. Found: C, 72.07; H, 9.01; N, 5.19%.

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

Procedure: Following the procedure of Example 1, step 3, 1.04 g (7.19 mmol) of 1-methyl-3,4-dihydronaphthalene in 7 ml of acetic acid was reacted with 2.33 ml of 37% formaldehyde solution and 1.58 g of propylamine hydrochloride. Work up gave 1.98 g of crude 1,2,3,4,5,6-hexahydro-3-propyl-benz[f]isoquinoline. Following the procedure of Example 2, this was reacted with 0.435 g of lithium wire in 250 ml of liquid ammonia, 40 ml of anhydrous THF and 1 ml of aniline. Chromatography on flash silica, eluting with 5-10% methanol/dichloromethane, then on alumina, eluting with 2-5% ethyl acetate/petroleum ether, gave 0.497 g (30%) of the title product as a colourless oil. The hydrochloride salt was made using ethereal hydrogen chloride. Upon evaporation of the solvent, the title product hydrochloride was obtained as a white solid, m.p. 257°-259° C. (dec). NMR δ(D2O) 1.00 (3H, t, J=7.4 Hz), 1.57 (1H, m), 1.68-1.92 (5H, m), 2.66-2.76 (2H, m), 2.87-2.95 (3H, m), 3.12-3.16 (3H, m), 3.63 (1H, m), 3.77 (1H, m), 7.22-7.31 (3H, m), 7.35-7.38 (1H, m). m/z (CI+, NH3) 230 (M+H)+, 200 (M-CH2CH3)+. Analysis calcd. for C16H24ClN: C, 72.29; H, 9.10; N, 5.27%. Found: C, 72.07; H, 9.01; N, 5.19%.

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

Procedure: Following the procedure of Example 1, step 3, 1.00 g (6.93 mmol) of 1-methyl-3,4-dihydronaphthalene in 7 ml of acetic acid was reacted with 2.25 ml of 37% formaldehyde solution and 2.16 g of cyclohexylamine hydrochloride. Work up gave 2.41 g of crude 3-cyclohexyl-1,2,3,4,5,6-hexahydro-benz[f]isoquinoline. Following the procedure of Example 2, this was reacted with 0.397 g of lithium wire in 200 ml of liquid ammonia, 40 ml of anhydrous THF and 1 ml of aniline. Chromatography on silica, eluting with 5-10% methanol/dichloromethane, then on alumina, eluting with 5-7% ethyl acetate/petroleum ether gave 0.333 g (18%) of the title product as a white solid. The hydrochloride salt was made using ethereal hydrogen chloride. Upon evaporation of the solvent, the title product hydrochloride was obtained as a white solid, m.p. 281°-285° C. (dec). NMR δ(D2O) 1.16-1.96 (12H, m), 2.10 (2H, m), 2.69 (2H, m), 2.92-3.05 (3H, m), 3.20-3.31 (2H, m), 3.55 (1H, m), 3.69 (1H, m), 7.25-7.29 (3H, m), 7.35-7.36 (1H, m). m/z (CI+, NH3) 270 (M+H)+, 226.

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

Procedure: Following the procedure of Example 1, step 3, 1.00 g (6.93 mmol) of 1-methyl-3,4-dihydronaphthalene in 7 ml of acetic acid was reacted with 2.25 ml of 37% formaldehyde solution and 2.16 g of cyclohexylamine hydrochloride. Work up gave 2.41 g of crude 3-cyclohexyl-1,2,3,4,5,6-hexahydro-benz[f]isoquinoline. Following the procedure of Example 2, this was reacted with 0.397 g of lithium wire in 200 ml of liquid ammonia, 40 ml of anhydrous THF and 1 ml of aniline. Chromatography on silica, eluting with 5-10% methanol/dichloromethane, then on alumina, eluting with 5-7% ethyl acetate/petroleum ether gave 0.333 g (18%) of the title product as a white solid. The hydrochloride salt was made using ethereal hydrogen chloride. Upon evaporation of the solvent, the title product hydrochloride was obtained as a white solid, m.p. 281°-285° C. (dec). NMR δ(D2O) 1.16-1.96 (12H, m), 2.10 (2H, m), 2.69 (2H, m), 2.92-3.05 (3H, m), 3.20-3.31 (2H, m), 3.55 (1H, m), 3.69 (1H, m), 7.25-7.29 (3H, m), 7.35-7.36 (1H, m). m/z (CI+, NH3) 270 (M+H)+, 226.

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

Procedure: Following the procedure of Example 1, step 3, 10 g (70 mmol) of 1-methyl-3,4-dihydronaphthalene and 22.55 g (278 mmol) of 37% formaldehyde solution in 60 ml of acetic acid were reacted with 10.8 g (0.16 mol) of methylamine hydrochloride. Chromatography on flash silica, eluting with 10% methanol/dichloromethane gave 6.0 g (44%) of the title product as a yellow oil. The hydrochloride salt was made using ethereal hydrogen chloride. Upon evaporation of the solvent and recrystallisation from ethyl acetate/ethanol, the title product hydrochloride was obtained, m.p. 198°-200° C. NMR δ(D2O) 2.23 (2H, t), 2.74-3.01 (7H, m), 3.35 (1H, m), 3.72 (1H, m), 3.90-3.95 (2H, m), 7.27-7.33 (4H, m). m/z (FAB+) 200 (M+H)+. Chromatography on flash silica, eluting with 10% methanol/dichloromethane

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

Procedure: A solution of 101.9 g (0.628 mol) of 1-hydroxy-1-methyl-1,2,3,4-tetrahydronaphthalene and 1.3 g of p-toluenesulphonic acid monohydrate in 1.3 liters of toluene was heated to reflux for 3 h with water being collected by means of a Dean Stark trap. The reaction mixture was cooled, washed with water (3×400 ml), then with saturated sodium chloride solution (400 ml), dried (K2CO3) and evaporated in vacuo to leave 126.4 g of brown liquid. This was vacuum distilled to yield 78.6 g (87%) of the title product as a pale yellow oil, b.p. 59°-62° C./1 mm of Hg. NMR δ(CDCl3) 2.06 (3H, m), 2.26 (2H, m), 2.76 (2H, t), 5.86 (1H, m), 7.11-7.27 (4H, m). collected by means of a Dean Stark trap The reaction mixture was cooled washed with water (3×400 ml) with saturated sodium chloride solution (400 ml), dried (K2CO3) evaporated in vacuo

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

Procedure: α-Tetralone was reacted with methylmagnesium iodide as described in J. Org. Chem., 26, 4165 (1961), without isolation of the intermediate 1-methyl-1-tetralol, to give the desired product, after distillation, in 68% yield as a colorless oil, boiling point 55-57° C. at 0.8 mm Hg.

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

Procedure: α-Tetralone was reacted with methylmagnesium iodide as described in J. Org. Chem., 26, 4165 (1961), without isolation of the intermediate 1-methyl-1-tetralol, to give the desired product, after distillation, in 68% yield as a colorless oil, boiling point 55-57° C. at 0.8 mm Hg.