2-(chloromethyl)benzenesulfonamide

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

Procedure: A mixtue of 2-(chloromethyl)benzenesulfonamide (13.2 g, 64 mmol) and butyl isocyanate (7.0 g, 71 mmol) in xylene (80 ml) was contacted with diazabicyclo[2.2.2]-octane (0.25 g) and heated to reflux for 5.0 hrs. Volatiles were removed under vacuum and the residue was treated with 0.5N NaOH (200 ml) and extracted with ethyl acetate (75 ml). The aqueous layer was separated, chilled, acidified (pH 4) with hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with brine, dried (MgSO4), and evaporated to give 14.6 g of white solid. A sample was recrystallized from toluene to give m.p. 104°-106°. heated to reflux for 5.0 hrs Volatiles were removed under vacuum the residue was treated with 0.5N NaOH (200 ml) extracted with ethyl acetate (75 ml) The aqueous layer was separated chilled extracted with ethyl acetate The organic layer was washed with brine dried (MgSO4) evaporated

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

Procedure: A solution of 2-(chloromethyl)benzenesulfonamide (2.00 g, 10 mmol) in acetonitrile (20 ml) was contacted with pyrrolidine (1.6 ml, 20 mmol). After 1.0 hr at ambient temperature, the volatiles were removed under vacuum and the residue was treated with water (40 ml) and chilled. The resulting solid was pulverized, filtered, and dried to give 2.23 g of white solid, m.p. 110°-112°. the volatiles were removed under vacuum the residue was treated with water (40 ml) chilled filtered dried

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

Procedure: A solution of 2-(chloromethyl)benzenesulfonamide (2.00 g, 10 mmol) in acetonitrile (20 ml) was contacted with pyrrolidine (1.6 ml, 20 mmol). After 1.0 hr at ambient temperature, the volatiles were removed under vacuum and the residue was treated with water (40 ml) and chilled. The resulting solid was pulverized, filtered, and dried to give 2.23 g of white solid, m.p. 110°-112°. the volatiles were removed under vacuum the residue was treated with water (40 ml) chilled filtered dried

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

Procedure: A solution of ammonia (5.2 ml) in tetrahydrofuran (250 ml) at -70° was contacted rapidly with a solution of 2-(chloromethyl)benzenesulfonyl chloride (21.8 g) in tetrahydrofuran (125 ml). The stirred mixture was allowed to warm to 0° and volatiles were removed under vacuum. The residue was contacted with ethyl acetate and a small volume of water. The organic layer was dried (MgSO4) and evaporated to give 19.8 g of white solid, m.p. 156°-157.5°. Recrystallization from toluene/ethyl acetate gave a sample with m.p. 157°-160°. at -70° to warm to 0° volatiles were removed under vacuum The organic layer was dried (MgSO4) evaporated

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

Procedure: A solution of ammonia (5.2 ml) in tetrahydrofuran (250 ml) at -70° was contacted rapidly with a solution of 2-(chloromethyl)benzenesulfonyl chloride (21.8 g) in tetrahydrofuran (125 ml). The stirred mixture was allowed to warm to 0° and volatiles were removed under vacuum. The residue was contacted with ethyl acetate and a small volume of water. The organic layer was dried (MgSO4) and evaporated to give 19.8 g of white solid, m.p. 156°-157.5°. Recrystallization from toluene/ethyl acetate gave a sample with m.p. 157°-160°. at -70° to warm to 0° volatiles were removed under vacuum The organic layer was dried (MgSO4) evaporated

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

Procedure: A solution of 4,6-dichloro-1,3,5-triazin-2-yl isocyanate (3.10 g, 16.2 mmol) in acetonitrile (15 ml) was contacted with 2-(chloromethyl)benzene sulfonamide (3.34 g, 16.2 mmol) and stirred for 20 hrs at 25°. The mixture was heated at 50° for 2 hrs, cooled and filtered to provide 3.86 g, mp 162°-170°, which was contacted with sodium methoxide (30 mmol) in methanol (60 ml) at 20°-25° for 16 hrs. Water (100 ml) was added and the mixture was filtered and neutralized by addition of hydrochloric acid. Filtration and drying gave 2.20 g of white solid, mp 150°-152° (dec.). The mixture was heated at 50° for 2 hrs cooled filtered to provide 3.86 g, mp 162°-170°, which the mixture was filtered neutralized by addition of hydrochloric acid Filtration drying

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

Procedure: A solution of 4,6-dichloro-1,3,5-triazin-2-yl isocyanate (3.10 g, 16.2 mmol) in acetonitrile (15 ml) was contacted with 2-(chloromethyl)benzene sulfonamide (3.34 g, 16.2 mmol) and stirred for 20 hrs at 25°. The mixture was heated at 50° for 2 hrs, cooled and filtered to provide 3.86 g, mp 162°-170°, which was contacted with sodium methoxide (30 mmol) in methanol (60 ml) at 20°-25° for 16 hrs. Water (100 ml) was added and the mixture was filtered and neutralized by addition of hydrochloric acid. Filtration and drying gave 2.20 g of white solid, mp 150°-152° (dec.). The mixture was heated at 50° for 2 hrs cooled filtered to provide 3.86 g, mp 162°-170°, which the mixture was filtered neutralized by addition of hydrochloric acid Filtration drying

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

Procedure: With cooling, 7.9 g of 97% 1,8-diazabicyclo[5.4.0]undec-7-ene are added to a suspension of 5.7 g of 98% 2-mercaptopyrimidine in 50 ml of acetonitrile. To the yellowish solution so obtained are added 10.3 g of 2-chloromethylbenzenesulfonamide. The reaction solution is stirred for 70 hours at 20°-22° C. and then diluted with 1 liter of water. The precipitate is isolated by filtration and dried, affording 12.0 g (85% of theory) of 2-(2-sulfamoylphenylmethylthio)pyrimidine of m.p. 128°-130° C. With cooling To the yellowish solution so obtained The precipitate is isolated by filtration dried

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

Procedure: With cooling, 7.9 g of 97% 1,8-diazabicyclo[5.4.0]undec-7-ene are added to a suspension of 5.7 g of 98% 2-mercaptopyrimidine in 50 ml of acetonitrile. To the yellowish solution so obtained are added 10.3 g of 2-chloromethylbenzenesulfonamide. The reaction solution is stirred for 70 hours at 20°-22° C. and then diluted with 1 liter of water. The precipitate is isolated by filtration and dried, affording 12.0 g (85% of theory) of 2-(2-sulfamoylphenylmethylthio)pyrimidine of m.p. 128°-130° C. With cooling To the yellowish solution so obtained The precipitate is isolated by filtration dried

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

Procedure: With cooling, 7.9 g of 97% 1,8-diazabicyclo[5.4.0]undec-7-ene are added to a suspension of 6.2 g of 97% 4,5-dihydro-2-mercaptothiazole in 50 ml of acetonitrile. To the yellow solution so obtained are added 10.3 g of 2-chloromethylbenzenesulfonamide and the reaction mixture is stirred for 1 hour at 20°-25° C. The reaction solution is then diluted with about 1 liter of water. The precipitate is isolated by filtration and dried, affording 11.9 g (76% of theory) of 4,5-dihydro-2-(2-sulfamoylphenylmethylthio)thiazole of m.p. 123°-125° C. With cooling To the yellow solution so obtained The precipitate is isolated by filtration dried

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

Procedure: With cooling, 7.9 g of 97% 1,8-diazabicyclo[5.4.0]undec-7-ene are added to a suspension of 6.2 g of 97% 4,5-dihydro-2-mercaptothiazole in 50 ml of acetonitrile. To the yellow solution so obtained are added 10.3 g of 2-chloromethylbenzenesulfonamide and the reaction mixture is stirred for 1 hour at 20°-25° C. The reaction solution is then diluted with about 1 liter of water. The precipitate is isolated by filtration and dried, affording 11.9 g (76% of theory) of 4,5-dihydro-2-(2-sulfamoylphenylmethylthio)thiazole of m.p. 123°-125° C. With cooling To the yellow solution so obtained The precipitate is isolated by filtration dried

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

Procedure: With cooling, 7.9 g of 97% 1,8-diazabicyclo[5.4.0]undec-7-ene are added to a suspension of 5.7 g of 98% 2-mercaptopyrimidine in 50 ml of acetonitrile. To the yellowish solution so obtained are added 10.3 g of 2-chloromethylbenzenesulfonamide. The reaction solution is stirred for 70 hours at 20°-22° C. and then diluted with 1 liter of water. The precipitate is isolated by filtration and dried, affording 12.0 g (85% of theory) of 2-(2-sulfamoylphenylmethylthio)pyrimidine of m.p. 128°-130° C. With cooling To the yellowish solution so obtained The precipitate is isolated by filtration dried