2,6-dichloro-3-methylaniline

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 50 ml of benzene, 4.0 g (22.7 mmole) of 2,6-dichloro-3-methylaniline, 10.67 ml (80.8 mmole) of trimethylsilyl bromide, and 13.1 ml (94.0 mmole) of triethylamine was heated at reflux over 42 hours. The product was isolated as described in Example 1 to provide 4.14 g (16.7 mmole, 73.5 percent yield) of 98.0 percent pure N-trimethylsilyl-2,6-dichloro-3-methylaniline as a light yellow oil, b.p. 64°-68° C. at 0.03 mm. at reflux over 42 hours The product was isolated

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

Procedure: A solution of sodium nitrite (12.0 g) in water was added to a stirred suspension of 2,6-dichloro-3-methylaniline (30.0 g) in a mixture of glacial acetic acid and concentrated hydrochloric acid. While maintaining the temperature below 10° C. The mixture was stirred at 0° C. for three quarters of an hour then added to a mixture of dimethyl disulphide (20 ml) and copper powder (0.25 g) in glacial acetic acid. The mixture was stirred for 4 hours and extracted with ether. The organic layer was washed with aqueous sodium carbonate (2M), water, dried (Na2SO4) and filtered. The filtrate was evaporated to dryness to give 2,4-dichloro-3-(methylsulphenyl)toluene (27.2 g) as a red liquid NMR (CDCl3) 2.4(s,3H), 2.45(s,3H), 7.15(d,1H), 7.3(d,1H). While maintaining the temperature below 10° C The mixture was stirred for 4 hours extracted with ether The organic layer was washed with aqueous sodium carbonate (2M), water dried (Na2SO4) filtered The filtrate was evaporated to dryness

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

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

Conditions: temp:15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-Acetylamino-3-mercapto-1,2,4-triazole (15.6 g, 0.10 mole) was added to 250 ml of acetic acid containing 3.6 g (0.20 mole) of water. The mixture was cooled to 15° C. with an external ice bath and 21 g (0.30 mole) of chlorine was added as a gas under the surface of the liquid with stirring over a 30 min. period. About 200 ml of volatiles were then removed from the mixture by evaporation under reduced pressure at up to 120° C. The residue was combined with 17.6 g (0.10 mole) of 2,6-dichloro-3-methylaniline and the mixture heated with stirring at 115° C. for 9 hours. A 100 ml portion of water and 25 ml of concentrated aqueous hydrochloric acid were added and the mixture heated at reflux for 12 hours. It was then allowed to cool and the solids present were collected by filtration. The solids were then placed in 200 ml of 10 percent aqueous sodium hydroxide and the insoluble fraction removed by filtration. The filtrate was acidfied with aqueous hydrochloric acid to pH 4.5 and the solids that formed were recovered by filtration and dried under reduced pressure to obtain 8.9 g (20 percent of theory) of the title compound assaying 80 percent purity by high pressure liquid chromatography. About 200 ml of volatiles were then removed from the mixture by evaporation under reduced pressure at up to 120° C the mixture heated with stirring at 115° C. for 9 hours the mixture heated at reflux for 12 hours to cool the solids present were collected by filtration the insoluble fraction removed by filtration the solids that formed were recovered by filtration dried under reduced pressure

Conditions: temp:15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-Acetylamino-3-mercapto-1,2,4-triazole (15.6 g, 0.10 mole) was added to 250 ml of acetic acid containing 3.6 g (0.20 mole) of water. The mixture was cooled to 15° C. with an external ice bath and 21 g (0.30 mole) of chlorine was added as a gas under the surface of the liquid with stirring over a 30 min. period. About 200 ml of volatiles were then removed from the mixture by evaporation under reduced pressure at up to 120° C. The residue was combined with 17.6 g (0.10 mole) of 2,6-dichloro-3-methylaniline and the mixture heated with stirring at 115° C. for 9 hours. A 100 ml portion of water and 25 ml of concentrated aqueous hydrochloric acid were added and the mixture heated at reflux for 12 hours. It was then allowed to cool and the solids present were collected by filtration. The solids were then placed in 200 ml of 10 percent aqueous sodium hydroxide and the insoluble fraction removed by filtration. The filtrate was acidfied with aqueous hydrochloric acid to pH 4.5 and the solids that formed were recovered by filtration and dried under reduced pressure to obtain 8.9 g (20 percent of theory) of the title compound assaying 80 percent purity by high pressure liquid chromatography. About 200 ml of volatiles were then removed from the mixture by evaporation under reduced pressure at up to 120° C the mixture heated with stirring at 115° C. for 9 hours the mixture heated at reflux for 12 hours to cool the solids present were collected by filtration the insoluble fraction removed by filtration the solids that formed were recovered by filtration dried under reduced pressure

Conditions: temp:12.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 11.6 g (0.10 mole) of 5-amino-3-mercapto-1,2,4-triazole, 12.75 g (0.0125 moles) of acetic anhydride and 100 ml of acetic acid was prepared and heated at reflux with stirring for 12 hours. Another 50 ml of acetic acid and 10 ml of water were then added and the mixture was cooled to 12° C. Chlorine (21 g, 0.3 mole) was then added to the mixture with stirring over a 15 min. period at 12°-20° C. A yellow solution was obtained. About 100 ml of volatiles were removed by distillation at 50° C. under reduced pressure. The resulting residue was combined with 2,6-dichloro-3-methylaniline (14.1 g, 0.080 mole) and the mixture heated at 115° C. for 4 hours with stirring. Concentrated aqueous hydrochloric acid (50 ml) was then added and the mixture was heated at reflux with stirring for another 5 hours. It was then allowed to cool to ambient temperature and the solids present were collected by filtration. The collected solids were placed in 200 ml of 10 percent aqueous sodium hydroxide. The insoluble material was removed by filtration and the pH of the filtrate was adjusted to 4.5 with hydrochloric acid to reprecipitate the title compound. The solids were recovered by filtration, washed with water, and dried under reduced pressure to obtain 10.1 g (28.9 percent of theory) of the title compound assaying 95 percent by high pressure liquid chromatography. was prepared heated at reflux with stirring over a 15 min. period at 12°-20° C A yellow solution was obtained About 100 ml of volatiles were removed by distillation at 50° C. under reduced pressure the mixture heated at 115° C. for 4 hours with stirring the mixture was heated at reflux with stirring for another 5 hours to cool to ambient temperature the solids present were collected by filtration The insoluble material was removed by filtration The solids were recovered by filtration washed with water dried under reduced pressure

Conditions: temp:12.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 11.6 g (0.10 mole) of 5-amino-3-mercapto-1,2,4-triazole, 12.75 g (0.0125 moles) of acetic anhydride and 100 ml of acetic acid was prepared and heated at reflux with stirring for 12 hours. Another 50 ml of acetic acid and 10 ml of water were then added and the mixture was cooled to 12° C. Chlorine (21 g, 0.3 mole) was then added to the mixture with stirring over a 15 min. period at 12°-20° C. A yellow solution was obtained. About 100 ml of volatiles were removed by distillation at 50° C. under reduced pressure. The resulting residue was combined with 2,6-dichloro-3-methylaniline (14.1 g, 0.080 mole) and the mixture heated at 115° C. for 4 hours with stirring. Concentrated aqueous hydrochloric acid (50 ml) was then added and the mixture was heated at reflux with stirring for another 5 hours. It was then allowed to cool to ambient temperature and the solids present were collected by filtration. The collected solids were placed in 200 ml of 10 percent aqueous sodium hydroxide. The insoluble material was removed by filtration and the pH of the filtrate was adjusted to 4.5 with hydrochloric acid to reprecipitate the title compound. The solids were recovered by filtration, washed with water, and dried under reduced pressure to obtain 10.1 g (28.9 percent of theory) of the title compound assaying 95 percent by high pressure liquid chromatography. was prepared heated at reflux with stirring over a 15 min. period at 12°-20° C A yellow solution was obtained About 100 ml of volatiles were removed by distillation at 50° C. under reduced pressure the mixture heated at 115° C. for 4 hours with stirring the mixture was heated at reflux with stirring for another 5 hours to cool to ambient temperature the solids present were collected by filtration The insoluble material was removed by filtration The solids were recovered by filtration washed with water dried under reduced pressure

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 1 g (5.2 mmol) of 2,6-dichloro-3-methylaniline in 2 ml pyridine was added 1 g (4.7 mmol) of 5-formylamino-3-chlorosulfonyl-1,2,4-triazole over a period of 5 minutes. The mixture was heated with stirring to 70° C. for 4 hours. It was then cooled and dispersed between 25 ml of 1N aqueous sodium hydroxide and 50 ml of chloroform. The aqueous layer was recovered, extracted with more chloroform, and acidified with aqueous hydrochloric acid. The solids that formed were collected by filtration and dried to obtain 1.0 g (59 percent of theory) of the title compound, m.p. 275°-279° C. The infrared and carbon nmr spectra were consistent with the assigned structure. The mixture was heated It was then cooled The aqueous layer was recovered extracted with more chloroform The solids that formed were collected by filtration dried

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 1 g (5.2 mmol) of 2,6-dichloro-3-methylaniline in 2 ml pyridine was added 1 g (4.7 mmol) of 5-formylamino-3-chlorosulfonyl-1,2,4-triazole over a period of 5 minutes. The mixture was heated with stirring to 70° C. for 4 hours. It was then cooled and dispersed between 25 ml of 1N aqueous sodium hydroxide and 50 ml of chloroform. The aqueous layer was recovered, extracted with more chloroform, and acidified with aqueous hydrochloric acid. The solids that formed were collected by filtration and dried to obtain 1.0 g (59 percent of theory) of the title compound, m.p. 275°-279° C. The infrared and carbon nmr spectra were consistent with the assigned structure. The mixture was heated It was then cooled The aqueous layer was recovered extracted with more chloroform The solids that formed were collected by filtration dried