2-benzylisoindole-1,3-dione

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

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

Procedure: The compound (330 mg) obtained in Example 24-1 was dissolved in chloroform and then added with chlorosulfuric acid (manufactured by Kishida Chemical Co., Ltd.) (0.177 ml) under ice-cooling. The solution was stirred at room temperature for 2 days, and then concentrated and dried. The resultant was gradually added with phosphorus pentachloride (300 mg) and then heated to 80° C., followed by stirring for 4 hours. cooling concentrated dried The resultant was gradually added with phosphorus pentachloride (300 mg) heated to 80° C. by stirring for 4 hours

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

Procedure: Benzylamine (manufactured by Tokyo Kasei Kogyo Co., Ltd.) (1.00 g) was dissolved in purified water (20 ml) and then added with N-carbethoxyphthalimide (manufactured by Tokyo Kasei Kogyo Co., Ltd.) (3.06 g) and sodium carbonate (2.47 g), followed by stirring at room temperature for 3 hours. After completion of the reaction, the solution was filtered and the residue was washed with purified water and then dried under vacuum at 60° C., thereby obtaining the subject compound (1.82 g) as a white solid. After completion of the reaction the solution was filtered the residue was washed with purified water dried under vacuum at 60° C.

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under N2 atmosphere, 11.26 mL chlorosulfonic acid was cooled in an ice bath, and under stirring 10.00 g n-benzylphthalimide was added portionwise over a period of 20 min. The ice bath was removed and the mixture was heated to 60° C. for 30 min. After cooling to room temperature, the mixture was cautiously poured into ice water and extracted twice with chloroform. The combined organic layers were dried over MgSO4 and concentrated to a small volume. The product was obtained by trituration of the concentrate with PA to give 10.44 g (73%) of a white powder. 1H NMR (400 MHz, CDCl3) δ 4.95 (s, 2H), 7.67 (d, J=8.43 Hz, 2H), 7.73-7.78 (m, 2H), 7.85-7.90 (m, 2H), 8.00 (d, J=8.43 Hz, 2H). was added portionwise over a period of 20 min The ice bath was removed After cooling to room temperature the mixture was cautiously poured into ice water extracted twice with chloroform The combined organic layers were dried over MgSO4 concentrated to a small volume The product was obtained by trituration of the concentrate with PA

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

Procedure: The synthesis set up by Rizzardo and coworkers is of the greatest practical interest, and comprises the synthesis of N-benzylpthalimide from benzyl bromide and potassium phthalimide, followed by its alkylation with a Grignard reagent. In the synthesis of 1,1,3,3-tetramethylisoindoline, for example, the Grignard reagent was prepared starting from methyl iodide and magnesium using, as solvents, ethyl ether and toluene (in succession): after 4 hours at reflux, N-benzyl-1,1,3,3-tetramethylisoindoline is obtained (37% yield), which is then treated with hydrogen (4 atmospheres; room temperature) in glacial acetic acid and in the presence of palladium-based catalysts (5% on coal). After 3 hours of reaction, 1,1,3,3-tetramethylisoindoline is obtained (II, R═CH3) with a yield of 96% (P. G. Griffiths, G. Moad, E. Rizzardo, D. H. Solomon, “Australian Journal of Chemistry” 1983, 36, 397).

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

Procedure: The synthesis set up by Rizzardo and coworkers is of the greatest practical interest, and comprises the synthesis of N-benzylpthalimide from benzyl bromide and potassium phthalimide, followed by its alkylation with a Grignard reagent. In the synthesis of 1,1,3,3-tetramethylisoindoline, for example, the Grignard reagent was prepared starting from methyl iodide and magnesium using, as solvents, ethyl ether and toluene (in succession): after 4 hours at reflux, N-benzyl-1,1,3,3-tetramethylisoindoline is obtained (37% yield), which is then treated with hydrogen (4 atmospheres; room temperature) in glacial acetic acid and in the presence of palladium-based catalysts (5% on coal). After 3 hours of reaction, 1,1,3,3-tetramethylisoindoline is obtained (II, R═CH3) with a yield of 96% (P. G. Griffiths, G. Moad, E. Rizzardo, D. H. Solomon, “Australian Journal of Chemistry” 1983, 36, 397).

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-Benzylphthalimide is prepared as described in Example 2, starting with 10 g of phthalic anhydride, 7.3 cm3 of benzylamine and a catalytic amount of para-toluenesulfonic acid in 100 cm3 of toluene. The reaction mixture is heated at a temperature in the region of 140° C. for 3 hours and is then cooled to a temperature in the region of 20° C. The reaction mixture is taken up in 100 cm3 of saturated aqueous sodium bicarbonate solution and the aqueous phase is extracted twice with 100 cm3 of ethyl acetate. The organic extracts are combined, washed with 50 cm3 of brine, dried over magnesium sulfate, filtered and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue is dried in a desiccator under reduced pressure (2 kPa) at a temperature in the region of 20° C. 10.3 g of N-benzylphthalimide are thus obtained in the form of a white powder. (Rf=0.44, thin layer chromatography on silica gel, eluent: cyclohexane/ethyl acetate (75/25 by volume)). N-Benzylphthalimide is prepared is then cooled to a temperature in the region of 20° C the aqueous phase is extracted twice with 100 cm3 of ethyl acetate washed with 50 cm3 of brine dried over magnesium sulfate filtered concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C The residue is dried in a desiccator under reduced pressure (2 kPa) at a temperature in the region of 20° C

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Hydroxy-2-benzyl-2,3-dihydroisoindol-1-one is prepared as described in Example 1, starting with 10.2 g of N-benzylphthalimide in 100 cm3 of methanol and 2.6 g of potassium borohydride. The reaction mixture is stirred at a temperature in the region of 20° C. for 20 hours and is then cooled to a temperature in the region of 0° C. and 50 cm3 of distilled water are added dropwise. The methanol is then partially evaporated off under reduced pressure (2 kPa) at a temperature in the region of 40° C., followed by addition of a further 50 cm3 of distilled water. The aqueous phase is extracted 3 times with 50 cm3 of ethyl acetate. The organic extracts are combined, washed with 50 cm3 of brine, dried over magnesium sulfate, filtered and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue is dried in a desiccator under reduced pressure (2 kPa) at a temperature in the region of 20° C. 9.5 g of 3-hydroxy-2-benzyl-2,3-dihydroisoindol-1-one are thus obtained in the form of a white powder. (Rf=0.20, thin layer chromatography on silica gel, eluent: cyclohexane/ethyl acetate (75/25 by volume)). 3-Hydroxy-2-benzyl-2,3-dihydroisoindol-1-one is prepared are added dropwise The methanol is then partially evaporated off under reduced pressure (2 kPa) at a temperature in the region of 40° C. followed by addition of a further 50 cm3 of distilled water The aqueous phase is extracted 3 times with 50 cm3 of ethyl acetate washed with 50 cm3 of brine dried over magnesium sulfate filtered concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C The residue is dried in a desiccator under reduced pressure (2 kPa) at a temperature in the region of 20° C

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

Procedure: The compound (330 mg) obtained in Example 24-1 was dissolved in chloroform and then added with chlorosulfuric acid (manufactured by Kishida Chemical Co., Ltd.) (0.177 ml) under ice-cooling. The solution was stirred at room temperature for 2 days, and then concentrated and dried. The resultant was gradually added with phosphorus pentachloride (300 mg) and then heated to 80° C., followed by stirring for 4 hours. cooling concentrated dried The resultant was gradually added with phosphorus pentachloride (300 mg) heated to 80° C. by stirring for 4 hours

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

Procedure: Benzylamine (manufactured by Tokyo Kasei Kogyo Co., Ltd.) (1.00 g) was dissolved in purified water (20 ml) and then added with N-carbethoxyphthalimide (manufactured by Tokyo Kasei Kogyo Co., Ltd.) (3.06 g) and sodium carbonate (2.47 g), followed by stirring at room temperature for 3 hours. After completion of the reaction, the solution was filtered and the residue was washed with purified water and then dried under vacuum at 60° C., thereby obtaining the subject compound (1.82 g) as a white solid. After completion of the reaction the solution was filtered the residue was washed with purified water dried under vacuum at 60° C.

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

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under N2 atmosphere, 11.26 mL chlorosulfonic acid was cooled in an ice bath, and under stirring 10.00 g n-benzylphthalimide was added portionwise over a period of 20 min. The ice bath was removed and the mixture was heated to 60° C. for 30 min. After cooling to room temperature, the mixture was cautiously poured into ice water and extracted twice with chloroform. The combined organic layers were dried over MgSO4 and concentrated to a small volume. The product was obtained by trituration of the concentrate with PA to give 10.44 g (73%) of a white powder. 1H NMR (400 MHz, CDCl3) δ 4.95 (s, 2H), 7.67 (d, J=8.43 Hz, 2H), 7.73-7.78 (m, 2H), 7.85-7.90 (m, 2H), 8.00 (d, J=8.43 Hz, 2H). was added portionwise over a period of 20 min The ice bath was removed After cooling to room temperature the mixture was cautiously poured into ice water extracted twice with chloroform The combined organic layers were dried over MgSO4 concentrated to a small volume The product was obtained by trituration of the concentrate with PA