1,3-dichloro-5-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:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred, -60° C. solution of 3,5-dichlorotoluene (805 mg, 5.00 mmol) in tetrahydrofuran (5 mL) under nitrogen atmosphere was treated dropwise over 10 minutes with a 1.6M solution of n-butyllithium in hexane (3.3 mL, 5.25 mmol). After addition was complete residual n-butyllithium in the addition funnel was rinsed into the reaction mixture with tetrahydrofuran (1 mL). The reaction mixture was stirred 30 minutes at -55° and then a solution of p-chlorobenzoylchloride (875 mg, 5.00 mmol) in tetrahydrofuran (1.0 mL) was added dropwise over 15 minutes. The mixture was kept at -55° to -30° C. for 2 hours, stirred 2 hours at ambient temperature, and quenched by addition of saturated aqueous ammonium chloride (1.1 mL). After stirring 15 minutes, sodium sulfate (1.1 g) was added, and the mixture was stirred an additional 15 minutes. The solution was decanted, the solids were washed with diethyl ether, and the combined solution and wash were evaporated under reduced pressure. The residue was recrystallized from ethanol (15 mL) to provide 0.78 g (52%) 4-(4-chlorobenzoyl)-3,5-dichlorotoluene. After addition was rinsed into the reaction mixture with tetrahydrofuran (1 mL) The mixture was kept at -55° to -30° C. for 2 hours stirred 2 hours at ambient temperature quenched by addition of saturated aqueous ammonium chloride (1.1 mL) After stirring 15 minutes sodium sulfate (1.1 g) was added the mixture was stirred an additional 15 minutes The solution was decanted the solids were washed with diethyl ether the combined solution and wash were evaporated under reduced pressure The residue was recrystallized from ethanol (15 mL)

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

Procedure: A stirred, -60° C. solution of 3,5-dichlorotoluene (805 mg, 5.00 mmol) in tetrahydrofuran (5 mL) under nitrogen atmosphere was treated dropwise over 10 minutes with a 1.6M solution of n-butyllithium in hexane (3.3 mL, 5.25 mmol). After addition was complete residual n-butyllithium in the addition funnel was rinsed into the reaction mixture with tetrahydrofuran (1 mL). The reaction mixture was stirred 30 minutes at -55° and then a solution of p-chlorobenzoylchloride (875 mg, 5.00 mmol) in tetrahydrofuran (1.0 mL) was added dropwise over 15 minutes. The mixture was kept at -55° to -30° C. for 2 hours, stirred 2 hours at ambient temperature, and quenched by addition of saturated aqueous ammonium chloride (1.1 mL). After stirring 15 minutes, sodium sulfate (1.1 g) was added, and the mixture was stirred an additional 15 minutes. The solution was decanted, the solids were washed with diethyl ether, and the combined solution and wash were evaporated under reduced pressure. The residue was recrystallized from ethanol (15 mL) to provide 0.78 g (52%) 4-(4-chlorobenzoyl)-3,5-dichlorotoluene. After addition was rinsed into the reaction mixture with tetrahydrofuran (1 mL) The mixture was kept at -55° to -30° C. for 2 hours stirred 2 hours at ambient temperature quenched by addition of saturated aqueous ammonium chloride (1.1 mL) After stirring 15 minutes sodium sulfate (1.1 g) was added the mixture was stirred an additional 15 minutes The solution was decanted the solids were washed with diethyl ether the combined solution and wash were evaporated under reduced pressure The residue was recrystallized from ethanol (15 mL)

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

Procedure: A stirred, -60° C. solution of 3,5-dichlorotoluene (805 mg, 5.00 mmol) in tetrahydrofuran (5 mL) under nitrogen atmosphere was treated dropwise over 10 minutes with a 1.6M solution of n-butyllithium in hexane (3.3 mL, 5.25 mmol). After addition was complete residual n-butyllithium in the addition funnel was rinsed into the reaction mixture with tetrahydrofuran (1 mL). The reaction mixture was stirred 30 minutes at -55° and then a solution of p-chlorobenzoylchloride (875 mg, 5.00 mmol) in tetrahydrofuran (1.0 mL) was added dropwise over 15 minutes. The mixture was kept at -55° to -30° C. for 2 hours, stirred 2 hours at ambient temperature, and quenched by addition of saturated aqueous ammonium chloride (1.1 mL). After stirring 15 minutes, sodium sulfate (1.1 g) was added, and the mixture was stirred an additional 15 minutes. The solution was decanted, the solids were washed with diethyl ether, and the combined solution and wash were evaporated under reduced pressure. The residue was recrystallized from ethanol (15 mL) to provide 0.78 g (52%) 4-(4-chlorobenzoyl)-3,5-dichlorotoluene. After addition was rinsed into the reaction mixture with tetrahydrofuran (1 mL) The mixture was kept at -55° to -30° C. for 2 hours stirred 2 hours at ambient temperature quenched by addition of saturated aqueous ammonium chloride (1.1 mL) After stirring 15 minutes sodium sulfate (1.1 g) was added the mixture was stirred an additional 15 minutes The solution was decanted the solids were washed with diethyl ether the combined solution and wash were evaporated under reduced pressure The residue was recrystallized from ethanol (15 mL)

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

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 1,3-dichloro-5-methylbenzene (2.0 g, 12.4 mmol) in THF (20 mL) was added n-BuLi (2.0 M in hexane, 9.3 mL, 18.6 mmol) at −78° C. dropwise over a period of 10 min and mixture was stirred at −78° C. for 30 min. A dry-ice was added to the reaction mixture slowly and the mixture was stirred at the same temperature for 20 min. Thereafter, the reaction mixture was slowly warmed to room temperature, quenched with 6 M HCl (10 mL) and extracted with EtOAc (2×30 mL). The combined organic layers were washed with water (50 mL), brine (50 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure to get compound A111-1 (1.1 g, 44%) as a white solid. the mixture was stirred at the same temperature for 20 min Thereafter, the reaction mixture was slowly warmed to room temperature quenched with 6 M HCl (10 mL) extracted with EtOAc (2×30 mL) The combined organic layers were washed with water (50 mL), brine (50 mL) dried over anhydrous Na2SO4 concentrated under reduced pressure to get compound A111-1 (1.1 g, 44%) as a white solid

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

Procedure: To a stirred, cold (-60° C.) solution of 3,5-dichlorotoluene (3.5 g, 21.7 mmol) in dry tetrahydrofuran (30 ml), 2.6 M n-butyllithium in hexane (8.78 ml, 22.8 mmol) was added dropwise over 15 minutes. The reaction mixture was stirred for one hour at -60° C. and then treated with a solution of 1-naphthoyl chloride (4.14 g, 21.7 mmol) in 15 ml of dry tetrahydrofuran over a period of 15 minutes. The mixture was stirred for 3.5 hours at -60° C. and then quenched with 4.8 ml of saturated NH4Cl solution. The mixture was permitted to warm to room temperature and then diluted with 30 ml of water and 30 ml of ether. The layers were thoroughly mixed and then separated. The etheral layer was backed-washed with brine and dried with anhydrous magnesium sulfate. Concentration afforded 7.12 g of crude product which was chromatographed on silica gel (20:1 hexane:ethyl acetate) to give 1.59 g (23 %). The mixture was stirred for 3.5 hours at -60° C. quenched with 4.8 ml of saturated NH4Cl solution to warm to room temperature diluted with 30 ml of water and 30 ml of ether The layers were thoroughly mixed separated The etheral layer was backed-washed with brine dried with anhydrous magnesium sulfate Concentration

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

Procedure: To a cold (-60° C.) stirred solution of 3,5-dichlorotoluene (2.5 g, 15.5 mmol) in 30 ml of dry tetrahydrofuran under a nitrogen atmosphere, a 2.6 M solution of n-butyllithium in hexane (6.3 ml, 16.3 mmol) was added slowly over 15 minutes. The reaction mixture was stirred for an additional 30 minutes at -60° C. and then treated dropwise with a solution of 2-naphthoyl chloride (2.95 g, 15.5 mmol) in 15 ml of dry tetrahydrofuran over 15 minutes. The reaction mixture was stirred for 4 hours at -60° C. and then quenched with 4 ml of saturated NH4Cl solution. The mixture was permitted to come to room temperature at which point it was diluted with 20 ml of water and 20 ml of ether. The layers were separated and the aqueous layer further extracted with ether. The combined extracts were washed with brine, dried with anhydrous magnesium sulfate and concentrated under reduced pressure to give 4.76 g of crude product. This material was chromatographed on silica gel (20:1 hexane:ethyl acetate) to give 1.71 g of pure product. The reaction mixture was stirred for 4 hours at -60° C. quenched with 4 ml of saturated NH4Cl solution to come to room temperature at which point it was diluted with 20 ml of water and 20 ml of ether The layers were separated the aqueous layer further extracted with ether The combined extracts were washed with brine dried with anhydrous magnesium sulfate concentrated under reduced pressure to give 4.76 g of crude product This material was chromatographed on silica gel (20:1 hexane:ethyl acetate)

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

Procedure: A stirred, -60° C. solution of 3,5-dichlorotoluene (805 mg, 5.00 mmol) in tetrahydrofuran (5 mL) under nitrogen atmosphere was treated dropwise over 10 minutes with a 1.6M solution of n-butyllithium in hexane (3.3 mL, 5.25 mmol). After addition was complete residual n-butyllithium in the addition funnel was rinsed into the reaction mixture with tetrahydrofuran (1 mL). The reaction mixture was stirred 30 minutes at -55° and then a solution of p-chlorobenzoylchloride (875 mg, 5.00 mmol) in tetrahydrofuran (1.0 mL) was added dropwise over 15 minutes. The mixture was kept at -55° to -30° C. for 2 hours, stirred 2 hours at ambient temperature, and quenched by addition of saturated aqueous ammonium chloride (1.1 mL). After stirring 15 minutes, sodium sulfate (1.1 g) was added, and the mixture was stirred an additional 15 minutes. The solution was decanted, the solids were washed with diethyl ether, and the combined solution and wash were evaporated under reduced pressure. The residue was recrystallized from ethanol (15 mL) to provide 0.78 g (52%) 4-(4-chlorobenzoyl)-3,5-dichlorotoluene. After addition was rinsed into the reaction mixture with tetrahydrofuran (1 mL) The mixture was kept at -55° to -30° C. for 2 hours stirred 2 hours at ambient temperature quenched by addition of saturated aqueous ammonium chloride (1.1 mL) After stirring 15 minutes sodium sulfate (1.1 g) was added the mixture was stirred an additional 15 minutes The solution was decanted the solids were washed with diethyl ether the combined solution and wash were evaporated under reduced pressure The residue was recrystallized from ethanol (15 mL)