1-chloro-2-methylbenzene

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:25.01; pressure:0.00; stir:

Procedure: General procedure C was applied to 1-chloro-2-methylbenzene 15e(51 mg, 0.4mmol). The reaction mixture was stirred at room temperature for 16hgiving a conversion of >99% (GC-MS) and 16eand17ein a 34:66mixture (1H NMR spectrum).

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

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

Procedure: According to the general procedure A, 2-chlorotoluene (66 mg, 0.52 mmol) reacted with benzylamine (68 mg, 0.64 mmol) using 1 mol % of Pd(dba)2, 2 mol % of Ph5FcP(t-Bu)2, and sodium tert-butoxide (60 mg, 0.63 mmol) in toluene at 100° C. for 4 h to give the title compound (99 mg, 96%) as a solid after recrystallization from hexane: 1H-NMR (300 MHz, CDCl3): δ 7.48-7.35 (m, 5H), 7.14 (m, 2H), 6.75 (t, 1H, J=7.2 and 7.5 Hz), 6.68 (d, 1H, J=7.8 Hz), 4.44 (s, 2H), 3.93 (bs, 1H), 2.24 (s, 3H). 13C{1H}-NMR (100 MHz, CDCl3): δ 146.01, 139.46, 130.02, 128.62, 127.50, 127.20, 127.12, 121.86, 117.13, 109.93, 48.26, 17.52. GC/MS(EI): m/z 197 (M+), 120, 106. Anal. Calcd for C14H15N: C, 85.24; H, 7.66; N, 7.10. Found: C, 84.98; H, 7.64; N, 7.20. at 100° C. for 4 h

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

Procedure: According to the general procedure B, 2-chlorotoluene (73 mg, 0.58 mmol) reacted with n-hexylamine (80 μl, 0.61 mmol) using 1 mol % of Pd(dba)2, 2 mol % of Ph5FcP(t-Bu)2, and sodium tert-butoxide (59 mg, 0.60 mmol) in toluene at 70° C. for 8 h to give the title compound (102 mg, 92%) as a colorless oil: 1H-NMR (300 MHz, CDCl3): δ 7.20 (t, 1H, J=7.5 and 7.8 Hz), 7.12 (d, 1H, J=7.2 Hz), 6.70 (dd, 2H, J=7.5 Hz), 3.51 (bs, 1H), 3.22 (t, 2H, J=7.2 Hz), 2.21 (s, 3H), 1.74 (m, 2H), 1.48 (m, 2H), 1.41 (m, 2H). 13C{1H}-NMR (100 MHz, CDCl3): δ 146.35, 129.94, 127.08, 121.60, 116.53, 109.52, 43.91, 31.64, 29.54, 26.90, 22.62, 17.43, 14.03. GC/MS(EI): m/z 191 (M+), 121. Anal. Calcd for C13H21N: C, 81.62; H, 11.06; N, 7.32. Found: C, 81.52; H, 11.09; N, 7.37. at 70° C. for 8 h

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

Procedure: According to the general procedure B, 2-chlorotoluene (129 mg, 1.02 mmol) reacted with N-methylaniline (133 mg, 1.20 mmol) using 0.5 mol % Pd(OAc)2, 1 mol % of Ph5FcP(t-Bu)2, and sodium tert-butoxide (120 mg, 1.25 mmol) in toluene at 100° C. to give the title compound (180 mg, 89%) as a colorless oil: 1H-NMR (400 MHz, CDCl3): δ 7.37-7.21 (m, 6H), 6.78 (t, 1H, J=7.25 Hz), 6.61 (d, 2H, J=7.86 Hz), 3.30 (s, 3H), 2.22 (s, 3H). 13C{1H}-NMR (100 MHz, CDCl3): δ 149.08, 146.74, 136.80, 131.32, 128.93, 128.30, 127.46, 126.38, 116.72, 112.76, 39.00, 17.83. GC/MS(EI): m/z 197 (M+). Anal. Calcd for C14H15N: C, 85.24; H, 7.66; N, 7.10. Found: C, 85.09; H, 7.71; N, 7.24. at 100° C.

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

Procedure: According to the general procedure A, 2-bromotoluene (188 mg, 1.10 mmol) reacted with diphenylamine (169 mg, 1.00 mmol) to give the title compound (258 mg, 99%) as a white solid at room temperature for 4 h. Reaction of 2-chlorotoluene (70 mg, 0.55 mmol) with diphenylamine (85 mg, 0.50 mmol) proceeded at 80° C. for 21 h to give the title compound (134 mg, 99%). 1H-NMR (400 MHz, CDCl3): δ 7.14-7.27 (m, 8H), 7.01-6.92 (m, 6H), 2.06 (s, 3H). 13C{1H}-NMR (100 MHz, CDCl3): δ 147.46, 145.37, 136.49, 131.67, 129.61, 128.99, 127.33, 125.95, 121.50, 121.33, 18.56. GC/MS(EI): m/z 259 (M+).

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

Procedure: A round-bottom flask was heated, and then allow to cool to room temperature under argon. To the flask were added Pd2(dba)3 (1.39 g, 1.52 mmol, 1.0 mol %) or Pd(dba)2 (1.38 g, 2.4 mmol, 1.4 mol %), 2-(di-tert-butylphosphino)biphenyl (1.09 g, 3.65 mmol, 2.4 mol %), 2-bromotoluene (12, 40 mL, 332.1 mmol) or 2-chlorotoluene (39 mL, 332.1 mmol), lithium amide (3.47 g, 151.1 mmol, 45 mol %), sodium t-butoxide 29.5 g, 297.7 mmol, 90 mol %), then toluene (150 mL). The reaction mixture was heated at 80° C. under argon overnight, then allowed to cool to room temperature. The resulting liquid was diluted with diethyl ether, and then filtered through a pad of celite. The resulting cocnentrte was filtered in vacuo and used in the next reaction without purification. The crude material was purified by column chromatography with hexane to give the product as white crystals with a yellow tint (23.4 g, 118.6 mmol, 72% yield). A round-bottom flask was heated The reaction mixture was heated at 80° C. under argon overnight to cool to room temperature filtered through a pad of celite The resulting cocnentrte was filtered in vacuo used in the next reaction without purification The crude material was purified by column chromatography with hexane

Conditions: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 216.00 g of aluminum chloride (mol. Wt. 133.34; 1,619.9 mmol), 109.09 g (4-Methylanisole (mol. Wt. 122.17; 892.9 mmol), and about 522.35 g of 2-chlorotoluene (mol. Wt. 126.59; 4,126.3 mmol) were charged to a 2 liter Parr®-brand 4522 stainless steel reaction vessel. To this mixture was added 5 drops of concentrated HCl. The vessel was sealed, heated to 30° C., and purged three times with carbon monoxide with the pressure of the vessel increased to 100 psi for each purging. After the third purge, the vessel was vented and a final introduction of CO was made at a pressure of about 550 psi, the pressure at which the reaction was maintained for the total reaction time of about 66 hours (the reaction temperature was maintained at 30° C. for the duration as well). Once the reaction was complete, the resultant mixture (exhibiting a dark orange color) was poured into about 500 mL of ice water (which turned the solution a yellow color), to which was added 500 mL of cyclohexane. The top, organic layer was removed and washed three times with water using a separatory funnel and dried over magnesium sulfate. The residual organic phase was then distilled under vacuum to remove excess cyclohexane, 2-chlorotoluene, and left about 76.01 g of a benzaldehyde mixture consisting of 4-chloro-3-methylbenzaldehyde (76.5%) and 3-chloro-4-methylbenzaldehyde (23.5%) (mol. Wt. 154.59; 491.7 mmol; yield of approximately 67.6%). The vessel was sealed purged three times with carbon monoxide with the pressure of the vessel increased to 100 psi for each purging After the third purge the pressure at which the reaction was maintained for the total reaction time of about 66 hours (the reaction temperature was maintained at 30° C. for the duration as well) was poured into about 500 mL of ice water (which was added 500 mL of cyclohexane The top, organic layer was removed washed three times with water using a separatory funnel dried over magnesium sulfate The residual organic phase was then distilled under vacuum to remove excess cyclohexane, 2-chlorotoluene left about 76.01 g of a benzaldehyde mixture

Conditions: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 216.00 g of aluminum chloride (mol. Wt. 133.34; 1,619.9 mmol), 109.09 g (4-Methylanisole (mol. Wt. 122.17; 892.9 mmol), and about 522.35 g of 2-chlorotoluene (mol. Wt. 126.59; 4,126.3 mmol) were charged to a 2 liter Parr®-brand 4522 stainless steel reaction vessel. To this mixture was added 5 drops of concentrated HCl. The vessel was sealed, heated to 30° C., and purged three times with carbon monoxide with the pressure of the vessel increased to 100 psi for each purging. After the third purge, the vessel was vented and a final introduction of CO was made at a pressure of about 550 psi, the pressure at which the reaction was maintained for the total reaction time of about 66 hours (the reaction temperature was maintained at 30° C. for the duration as well). Once the reaction was complete, the resultant mixture (exhibiting a dark orange color) was poured into about 500 mL of ice water (which turned the solution a yellow color), to which was added 500 mL of cyclohexane. The top, organic layer was removed and washed three times with water using a separatory funnel and dried over magnesium sulfate. The residual organic phase was then distilled under vacuum to remove excess cyclohexane, 2-chlorotoluene, and left about 76.01 g of a benzaldehyde mixture consisting of 4-chloro-3-methylbenzaldehyde (76.5%) and 3-chloro-4-methylbenzaldehyde (23.5%) (mol.wt. 154.59; 491.7 mmol; yield of approximately 67.6%). The vessel was sealed purged three times with carbon monoxide with the pressure of the vessel increased to 100 psi for each purging After the third purge the pressure at which the reaction was maintained for the total reaction time of about 66 hours (the reaction temperature was maintained at 30° C. for the duration as well) was poured into about 500 mL of ice water (which was added 500 mL of cyclohexane The top, organic layer was removed washed three times with water using a separatory funnel dried over magnesium sulfate The residual organic phase was then distilled under vacuum to remove excess cyclohexane, 2-chlorotoluene left about 76.01 g of a benzaldehyde mixture