2-benzyl-1,1,3,3-tetramethylisoindole

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: 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: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: A solution of 2-benzyl-1,1,3,3,-tetramethylisoindoline (5.5 g 20 mmol) in glacial acetic acid (20 ml) was hydrogenated at 60 lb/in2 over 5% palladium/c for 3 h at room temperature. The suspension was filtered and the solvent removed at reduced pressure. The residue was dissolved in water and the solution was made alkaline (PH 9) by the addition of 10% sodium hydroxide and extracted with ether (3×50 ml). The combined organic extracts were dried and evaporated to dryness to give the title compound (3.5 g 96%), which was recrystalized from methanol/water. m.p. 36-38° C. NMR (CDCl3, 400 MHz), 1.46 s, 4 x CH3; 1.9 s, NH, D2O exchanged; 7.1-7.27 m, ArH. for 3 h at room temperature The suspension was filtered the solvent removed at reduced pressure The residue was dissolved in water by the addition of 10% sodium hydroxide extracted with ether (3×50 ml) The combined organic extracts were dried evaporated to dryness

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

Procedure: (Griffiths, P. G. et al Synthesis of the radical scavenger 1,1,3,3-tetramethylisoindolin-2-yloxyl. Aust. J. Chem. 1983, 36, 397-401; Chan, K. S. et al. Reactions of nitroxides with metalloporphyrin alkyls bearing beta hydrogens: aliphatic carbon-carbon bond activation by metal centered radicals. J. Organomet. Chem. 2008, 693, 399-407). The protected benzyl-amine 16 (1.864 g, 7.02 mmol) was dissolved in AcOH (34 mL) in a Parr flask, and 10% Pd/C (169.5 mg) was added. (The reaction was splited in 3 batches.) The flask was placed in a high pressure reactor. The reactor was charged with H2 and purged for 5 cycles and was finally pressurized with H2 at 4 bars (60 psi). After stirring at rt for 3 h, the reaction mixture was filtered through Celite, and the solvent removed in vacuo. The resulting residue was dissolved in water (5 mL) and the solution neutralized with 2.5N NaOH (pH 11.5), and extracted with Et2O (3×50 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated in vacuo to yield 1.165 g (95%) of the crude title compound as slightly yellow crystals. mp 36.0-36.5° C. 1H NMR (300 MHz, CDCl3) δ 7.30-7.23 (m, 2 H), 7.18-7.11 (m, 2 H), 1.86 (bs, 1 H), 1.48 (s, 12 H). was added (The reaction was splited in 3 batches ) The flask was placed in a high pressure reactor The reactor was charged with H2 purged for 5 cycles the reaction mixture was filtered through Celite the solvent removed in vacuo The resulting residue was dissolved in water (5 mL) extracted with Et2O (3×50 mL) The combined organic layers were dried (Na2SO4) filtered concentrated in vacuo

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

Procedure: (Griffiths, P. G. et al. Synthesis of the radical scavenger 1,1,3,3-tetramethylisoindolin-2-yloxyl. Aust. J. Chem. 1983, 36, 397-401; Chan, K. S. et al. Reactions of nitroxides with metalloporphyrin alkyls bearing beta hydrogens: aliphatic carbon-carbon bond activation by metal centered radicals. J. Organomet. Chem. 2008, 693, 399-407). The protected benzyl-amine 16 (1.864 g, 7.02 mmol) was dissolved in AcOH (34 mL) in a Parr flask, and 10% Pd/C (169.5 mg) was added. (The reaction was splited in 3 batches.) The flask was placed in a high pressure reactor. The reactor was charged with H2 and purged for 5 cycles and was finally pressurized with H2 at 4 bars (60 psi). After stirring at rt for 3 h, the reaction mixture was filtered through Celite, and the solvent removed in vacuo. The resulting residue was dissolved in water (5 mL) and the solution neutralized with 2.5N NaOH (pH 11.5), and extracted with Et2O (3×50 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated in vacuo to yield 1.165 g (95%) of the crude title compound as slightly yellow crystals. mp 36.0-36.5° C. 1H NMR (300 MHz, CDCl3) δ 7.30-7.23 (m, 2H), 7.18-7.11 (m, 2H), 1.86 (bs, 1H), 1.48 (s, 12H). was added (The reaction was splited in 3 batches ) The flask was placed in a high pressure reactor The reactor was charged with H2 purged for 5 cycles the reaction mixture was filtered through Celite the solvent removed in vacuo The resulting residue was dissolved in water (5 mL) extracted with Et2O (3×50 mL) The combined organic layers were dried (Na2SO4) filtered concentrated in vacuo

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

Procedure: (Griffiths, P. G. et al. Synthesis of the radical scavenger 1,1,3,3-tetramethylisoindolin-2-yloxyl. Aust. J. Chem. 1983, 36, 397-401; Chan, K. S. et al. Reactions of nitroxides with metalloporphyrin alkyls bearing beta hydrogens: aliphatic carbon-carbon bond activation by metal centered radicals. J. Organomet. Chem. 2008, 693, 399-407). The protected benzyl-amine 16 (1.864 g, 7.02 mmol) was dissolved in AcOH (34 mL) in a Parr flask, and 10% Pd/C (169.5 mg) was added. (The reaction was split in 3 batches.) The flask was placed in a high pressure reactor. The reactor was charged with H2 and purged for 5 cycles and was finally pressurized with H2 at 4 bars (60 psi). After stirring at rt for 3 h, the reaction mixture was filtered through Celite, and the solvent removed in vacuo. The resulting residue was dissolved in water (5 mL) and the solution neutralized with 2.5N NaOH (pH 11.5), and extracted with Et2O (3×50 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated in vacuo to yield 1.165 g (95%) of the crude title compound as slightly yellow crystals. mp 36.0-36.5° C. 1H NMR (300 MHz, CDCl3) δ 7.30-7.23 (m, 2 H), 7.18-7.11 (m, 2H), 1.86 (bs, 1H), 1.48 (s, 12H). was added (The reaction was split in 3 batches ) The flask was placed in a high pressure reactor The reactor was charged with H2 purged for 5 cycles the reaction mixture was filtered through Celite the solvent removed in vacuo The resulting residue was dissolved in water (5 mL) extracted with Et2O (3×50 mL) The combined organic layers were dried (Na2SO4) filtered concentrated in vacuo

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

Procedure: (Griffiths, P. G. et al. Synthesis of the radical scavenger 1,1,3,3-tetramethylisoindolin-2-yloxyl. Aust. J. Chem. 1983, 36, 397-401; Chan, K. S. et al. Reactions of nitroxides with metalloporphyrin alkyls bearing beta hydrogens: aliphatic carbon-carbon bond activation by metal centered radicals. J. Organomet. Chem. 2008, 693, 399-407). The protected benzyl-amine 16 (1.864 g, 7.02 mmol) was dissolved in AcOH (34 mL) in a Parr flask, and 10% Pd/C (169.5 mg) was added. (The reaction was splited in 3 batches). The flask was placed in a high pressure reactor. The reactor was charged with H2 and purged for 5 cycles and was finally pressurized with H2 at 4 bars (60 psi). After stirring at rt for 3 h, the reaction mixture was filtered through Celite, and the solvent removed in vacuo. The resulting residue was dissolved in water (5 mL) and the solution neutralized with 2.5N NaOH (pH 11.5), and extracted with Et2O (3×50 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated in vacuo to yield 1.165 g (95%) of the crude title compound as slightly yellow crystals. mp 36.0-36.5° C. 1H NMR (300 MHz, CDCl3) δ 7.30-7.23 (m, 2 H), 7.18-7.11 (m, 2 H), 1.86 (bs, 1 H), 1.48 (s, 12 H). was added (The reaction was splited in 3 batches) The flask was placed in a high pressure reactor The reactor was charged with H2 purged for 5 cycles the reaction mixture was filtered through Celite the solvent removed in vacuo The resulting residue was dissolved in water (5 mL) extracted with Et2O (3×50 mL) The combined organic layers were dried (Na2SO4) filtered concentrated in vacuo

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).