2,4,6-trichloroaniline

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

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

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,4,6-trichloroaniline, 49.1 gm, was added to 250 ml of methylene chloride. The system was cooled to 0° C. and 34.8 ml of triethylamine was then added. After addition of the triethylamine, 21.8 ml of bromacetylbromide was added. The system was allowed to warm to room temperature and stirred there for 18 hours. The reaction was then stopped and the solvent was washed with saturated sodium bicarbonate solution. The methylene chloride layer was separated and partially stripped when a solid precipitated from solution. The solid was filtered and air dried to yield 41.4 gm of α-bromo-(2,4,6-trichlorophenyl) acetamide as a gray solid. was added to warm to room temperature the solvent was washed with saturated sodium bicarbonate solution The methylene chloride layer was separated precipitated from solution The solid was filtered air dried

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

Procedure: In the manner described in example 3, 2-bromophenylacetic acid is condensed with 2,4,6-trichloroaniline to yield 2-[(2,4,6-trichlorophenyl)amino]phenylacetic acid.

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

Procedure: In the manner described in example 3, 2-bromophenylacetic acid is condensed with 2,4,6-trichloroaniline to yield 2-[(2,4,6-trichlorophenyl)amino]phenylacetic acid.

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

Procedure: Sodium naphthalene was prepared from naphthalene (12.8 g., 0.1 mole), sodium (2.3 g., 0.1 g atom) and tetrahydrofuran (200 ml.). Thereafter, 2,4,6-trichloroaniline (19.6 g., 0.1 mole) was added under nitrogen at ice bath temperature.

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

Procedure: Sodium naphthalene was prepared from naphthalene (12.8 g., 0.1 mole), sodium (2.3 g., 0.1 g atom) and tetrahydrofuran (200 ml.). Thereafter, 2,4,6-trichloroaniline (19.6 g., 0.1 mole) was added under nitrogen at ice bath temperature.

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

Procedure: A mixture of 2,4,6-trichloroaniline (1.20g, 6.11 mmol), maleic anhydride (0.80g, 8.2 mmol) and tin(II) chloride (0.068g, 0.36 mmol) is heated to 140° C. with mixing and held at this temperature for 2.0 hours. The reaction mixture is cooled, extracted with xylene, filtered and the resulting filtrate water washed. Solvent removal yielded N-(2,4,6-trichlorophenyl)maleimide. HPLC analysis showed conversion of 2,4,6-trichloroaniline was 96.4% and selectivity to N-(2,4,6-trichlorophenyl)maleimide based on reacted 2,4,6-trichloroaniline was 88.0%. with mixing The reaction mixture is cooled extracted with xylene filtered the resulting filtrate water washed Solvent removal

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

Procedure: A mixture of 2,4,6-trichloroaniline (1.20g, 6.11 mmol), maleic anhydride (0.80g, 8.2 mmol) and tin(II) chloride (0.068g, 0.36 mmol) is heated to 140° C. with mixing and held at this temperature for 2.0 hours. The reaction mixture is cooled, extracted with xylene, filtered and the resulting filtrate water washed. Solvent removal yielded N-(2,4,6-trichlorophenyl)maleimide. HPLC analysis showed conversion of 2,4,6-trichloroaniline was 96.4% and selectivity to N-(2,4,6-trichlorophenyl)maleimide based on reacted 2,4,6-trichloroaniline was 88.0%. with mixing The reaction mixture is cooled extracted with xylene filtered the resulting filtrate water washed Solvent removal

Conditions: temp:12.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of paratoluene sulfonic acid monohydrate (14.5 g; 76.4 mmol) in acetonitrile (100 ml) was added the 2,4,6-trichloroaniline (5.0 g; 25.5 mmol). The resulting white suspension was cooled to 10-15° C. and to this was added, gradually a solution of sodium nitrite (3.5 g; 51.0 mmol) and potassium iodide (10.6 g; 63.6 mmol) in water (15 ml), the suspension became dark brown, thick and gas release was observed. The thick mixture was stirred for 10 min at 10° C. and then temperature was allowed to increase to 20° C. The solution obtained was stirred for 1 h. The solution was poured in water, 1M sodium hydrogen carbonate solution was added (pH adjusted to 9-10) and 2M solution of sodium thiosulfate was added. The mixture was extracted three times with dichloromethane. Organics were combined, dried over sodium sulfate and the solvent was removed in vacuo to provide a resin which was subject to flash column chromatography (eluant: c-hexane). 6.3 g (80% of theory) of 1,3,5-trichloro-2-iodo-benzene was obtained as a white solid. to this was added to increase to 20° C The solution obtained was stirred for 1 h was added The mixture was extracted three times with dichloromethane dried over sodium sulfate the solvent was removed in vacuo to provide a resin which

Conditions: temp:12.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of paratoluene sulfonic acid monohydrate (14.5 g; 76.4 mmol) in acetonitrile (100 ml) was added the 2,4,6-trichloroaniline (5.0 g; 25.5 mmol). The resulting white suspension was cooled to 10-15° C. and to this was added, gradually a solution of sodium nitrite (3.5 g; 51.0 mmol) and potassium iodide (10.6 g; 63.6 mmol) in water (15 ml), the suspension became dark brown, thick and gas release was observed. The thick mixture was stirred for 10 min at 10° C. and then temperature was allowed to increase to 20° C. The solution obtained was stirred for 1 h. The solution was poured in water, 1M sodium hydrogen carbonate solution was added (pH adjusted to 9-10) and 2M solution of sodium thiosulfate was added. The mixture was extracted three times with dichloromethane. Organics were combined, dried over sodium sulfate and the solvent was removed in vacuo to provide a resin which was subject to flash column chromatography (eluant: c-hexane). 6.3 g (80% of theory) of 1,3,5-trichloro-2-iodo-benzene was obtained as a white solid. to this was added to increase to 20° C The solution obtained was stirred for 1 h was added The mixture was extracted three times with dichloromethane dried over sodium sulfate the solvent was removed in vacuo to provide a resin which

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

Procedure: A solution (10.7 ml, 17.1 mmol) of 1.60M N-butyl-lithium in hexane was added to a solution of 3.20 g (16.3 mmol) of 2,4,6-trichloroaniline in 20 ml of dry THF cooled to -78° C. The resultant solution was then allowed to warm to room temperature. This solution was added to a solution of 2.00 g (8.11 mmol) of 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine-2-sulfonyl chloride in 30 ml of dry THF cooled to --10° C. The temperature of the reaction mixture was maintained between -13° C. and -9° C. during to course of the addition. After the addition was complete, the reaction mixture was stirred for 30 minutes and warmed to room temperature. After 1 hour at room temperature, THF was removed from the reaction mixture by evaporation. The residue was triturated with H2O and filtered. The filtrate was treated with charcoal and filtered through celite. The filtrate was washed with Et2O, and the aqueous phase was separated and acidified with 3N HCl to precipitate a solid. The solid was collected by filtration, washed with water and dried in vacuo to yield 0.70 g (21%) of the desired product as a tan solid, m.p. >200° C. (decomp.) 1H NMR and IR spectra were consistent with the assigned structure. to warm to room temperature cooled to --10° C The temperature of the reaction mixture was maintained between -13° C. and -9° C. during to course of the addition After the addition warmed to room temperature After 1 hour at room temperature THF was removed from the reaction mixture by evaporation The residue was triturated with H2O filtered The filtrate was treated with charcoal filtered through celite The filtrate was washed with Et2O the aqueous phase was separated to precipitate a solid The solid was collected by filtration washed with water dried in vacuo