1-bromo-2,3-dichlorobenzene

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:36.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 163 g 2,3-Dichloroaniline (1.0 mol) is added to a mixture of 3250 g of 30% aqueous HBr (12.0 mole) and 25.4 g copper powder of a particle size of approx. 45μ at 35-37° C. The mixture is stirred for 15 minutes at 35-37° C. Then, 766 g of an aqueous solution of NaNO2 (40% solution in water, 4.44 mole) is added via subsurface feeding over a period of 3 hours at 35° C. Parallel to the addition of the sodium nitrite 489 g 2,3-dichloroaniline (3.0 mol) is added over a period of 2.5 hours at the same temperature. The addition of dichloraniline starts 15 minutes after the start of the addition of sodium nitrite. After all additions are complete the reaction mixture is stirred for 30 minutes at 35° C. Then, the reaction mixture is heated to 60-65° C. The organic phase containing the reaction product is separated from the aqueous phase. The remaining liquid is discarded and the crude product is washed twice with 200 ml water. 792.2 g of crude solid 1-bromo-2,3-dichlorobenzene is obtained (87.7% of theory) with a purity of 86.2%). feeding over a period of 3 hours at 35° C is added over a period of 2.5 hours at the same temperature starts 15 minutes is stirred for 30 minutes at 35° C Then, the reaction mixture is heated to 60-65° C The organic phase containing the reaction product is separated from the aqueous phase the crude product is washed twice with 200 ml water

Conditions: temp:35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 32.7 g 2,3-Dichloroaniline (0.20 mole) is added to a mixture of 21.4 g of NaBr (0.20 mole, 1.0 equivalent), 110.0 g of 48% aqueous HBr (0.66 mole, 3.3 equivalents) and 70 ml water at 30-40° C. The mixture is stirred for 15 minutes at 30-40° C. and then heated to 45° C. Then 5.1 g CuSO4*5H2O (0.02 mole, 0.10 equivalent) is added and the mixture is stirred for 15 minutes at 45° C. After this, an aqueous solution of NaNO2 (40% solution in water, 37.6 g, 0.22 mole, 1.1 equivalents) is added via subsurface feeding over a period of 2 hours at 45° C. The reaction mixture is stirred for 30 minutes at 45° C. After this, the reaction mixture is heated to 60-65° C. The organic phase containing the reaction product is separated from the aqueous phase and is cooled to ambient temperature, leading to solidification of the reaction product. The remaining liquid is discarded and the crude product is washed twice with 10 ml water and dried under vacuum. 44.0 g (83% of theory) of 1-bromo-2,3-dichlorobenzene is obtained in the form of a light brown solid (purity: 85%). heated to 45° C the mixture is stirred for 15 minutes at 45° C feeding over a period of 2 hours at 45° C The reaction mixture is stirred for 30 minutes at 45° C After this, the reaction mixture is heated to 60-65° C The organic phase containing the reaction product is separated from the aqueous phase is cooled to ambient temperature the crude product is washed twice with 10 ml water dried under vacuum

Conditions: temp:35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 32.7 g 2,3-Dichloroaniline (0.20 mole) is added to a mixture of 168.5 g of 48% aqueous HBr (1.0 mole, 5.0 equivalents) and 40 ml water at 30-40° C. The mixture is stirred for 15 minutes at 30-40° C. and then heated to 45° C. Then 2.9 g Cu(I)Br (0.02 mole, 0.10 equivalent) is added and the mixture is stirred for 15 minutes at 45° C. After this, an aqueous solution of NaNO2 (40% solution in water, 35.6 g, 0.21 mole, 1.0 equivalents) is added via subsurface feeding over a period of 2 hours at 45° C. The reaction mixture is stirred for 30 minutes at 45° C. After this, the reaction mixture is heated to 60-65° C. The organic phase containing the reaction product is separated from the aqueous phase and is cooled to ambient temperature, leading to solidification of the reaction product. The remaining liquid is discarded and the crude product is washed twice with 10 ml water and dried under vacuum. 40.0 g (80% of theory) of 1-bromo-2,3-dichlorobenzene is obtained in the form of a light brown solid (purity: 90%). heated to 45° C the mixture is stirred for 15 minutes at 45° C feeding over a period of 2 hours at 45° C The reaction mixture is stirred for 30 minutes at 45° C After this, the reaction mixture is heated to 60-65° C The organic phase containing the reaction product is separated from the aqueous phase is cooled to ambient temperature the crude product is washed twice with 10 ml water dried under vacuum

Conditions: temp:37.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 32.7 g 2,3-Dichloroaniline (0.20 mole) is added to a mixture of 21.4 g of NaBr (0.20 mole, 1.0 equivalent), 110.0 g of 48% aqueous HBr (0.66 mole, 3.3 equivalents) and 70 ml water at 30-45° C. The mixture is stirred for 15 minutes at 30-45° C. and then heated to 60° C. Then 2.9 g Cu(I)Br (0.02 mole, 0.10 equivalent) is added and the mixture is stirred for 15 minutes at 60° C. After this, an aqueous solution of NaNO2 (40% solution in water, 37.6 g, 0.22 mole, 1.1 equivalents) is added via subsurface feeding over a period of 2 hours at 60-65° C. The reaction mixture is stirred for 30 minutes at 60-65° C. The organic phase containing the reaction product is separated from the aqueous phase and is cooled to ambient temperature, leading to solidification of the reaction product. The remaining liquid is discarded and the crude product is washed two times with 10 ml water and dried under vacuum. 44.0 g (89% of theory) of 1-bromo-2,3-dichlorobenzene is obtained in the form of a light brown solid (purity: 91%). For further characterisation, the crude product was purified by vacuum distillation (130° C./20 mmHg). 38.0 g (84% of theory) of pure 1-bromo-2,3-dichlorobenzene is obtained in the form of white crystals. heated to 60° C the mixture is stirred for 15 minutes at 60° C feeding over a period of 2 hours at 60-65° C The reaction mixture is stirred for 30 minutes at 60-65° C The organic phase containing the reaction product is separated from the aqueous phase is cooled to ambient temperature the crude product is washed two times with 10 ml water dried under vacuum

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: To a slurry of 1-bromo-2,3-dichlorobenzene (1.46 g, 6.46 mmol) in diethyl ether (10 mL) was added magnesium (0.157 g, 6.46 mmol) and a crystal of iodine. This mixture was refluxed for 3 h, and then cooled to room temperature. A solution of benzyl (2R,5E)-2-[bis(tert-butoxycarbonyl)amino]-6-nitrohex-5-enoate (0.50 g, 1.08 mmol) in diethyl ether (10 mL) was cooled to 0° C., and 2.0 mL of the Grignard solution prepared above was added. After 1 and 2 h, respectively, 2.0 and 1.0 mL of the Grignard solution was added. The reaction was quenched with a saturated aqueous solution of ammonium chloride, the phases separated and the organic phase washed with saturated aqueous sodium potassium tartrate and brine. The combined organics were dried over magnesium sulfate, filtered and concentrated to give a residue that was purified by silica gel chromatography (0%→-3% methanol/dichloromethane) to give the title compound (0.52 g). MS 411.0 (M+1-2Boc). This mixture was refluxed for 3 h 2.0 mL of the Grignard solution prepared above was added After 1 and 2 h, respectively, 2.0 and 1.0 mL of the Grignard solution was added The reaction was quenched with a saturated aqueous solution of ammonium chloride the phases separated the organic phase washed with saturated aqueous sodium potassium tartrate and brine The combined organics were dried over magnesium sulfate filtered concentrated to give a residue that was purified by silica gel chromatography (0%→-3% methanol/dichloromethane)

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

Procedure: To a slurry of 1-bromo-2,3-dichlorobenzene (1.46 g, 6.46 mmol) in diethyl ether (10 mL) was added magnesium (0.157 g, 6.46 mmol) and a crystal of iodine. This mixture was refluxed for 3 h, and then cooled to room temperature. A solution of benzyl (2R,5E)-2-[bis(tert-butoxycarbonyl)amino]-6-nitrohex-5-enoate (0.50 g, 1.08 mmol) in diethyl ether (10 mL) was cooled to 0° C., and 2.0 mL of the Grignard solution prepared above was added. After 1 and 2 h, respectively, 2.0 and 1.0 mL of the Grignard solution was added. The reaction was quenched with a saturated aqueous solution of ammonium chloride, the phases separated and the organic phase washed with saturated aqueous sodium potassium tartrate and brine. The combined organics were dried over magnesium sulfate, filtered and concentrated to give a residue that was purified by silica gel chromatography (0%→-3% methanol/dichloromethane) to give the title compound (0.52 g). MS 411.0 (M+1-2Boc). This mixture was refluxed for 3 h 2.0 mL of the Grignard solution prepared above was added After 1 and 2 h, respectively, 2.0 and 1.0 mL of the Grignard solution was added The reaction was quenched with a saturated aqueous solution of ammonium chloride the phases separated the organic phase washed with saturated aqueous sodium potassium tartrate and brine The combined organics were dried over magnesium sulfate filtered concentrated to give a residue that was purified by silica gel chromatography (0%→-3% methanol/dichloromethane)

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

Procedure: Using the combinations of monobromodichlorobenzene or trichlorobenzene, thioglycolic acid, potassium hydroxide and solvent listed in Table 2, the reaction was carried out in the same manner as in Example 8 or 9 to yield 2,5-dichlorophenylthioglycolic acid. The results are given in Table 2.