N-phenylmethanesulfonamide

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:

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: Methanesulfonanilide as prepared in Preparation 1 (172.0 g, 1.0 mole), bromoacetylbromide (363.35 g, 1.8 mole), and 1 liter of carbon disulfide is combined under N2 with vigorous mechanical stirring. Anhydrous aluminum chloride (400.0 g, 3.0 mole) is added in portions to this mixture over 11/2 hour resulting in a deep red color and separation of the reaction mixture into two layers. Following the addition, the reaction is stirred at ambient temperature for 45 minutes and is then heated to reflux. After refluxing for 1 hour the oil bath is removed and the reaction is stirred at room temperature overnight. The two layers are allowed to separate and the upper layer is decanted. The viscous dark brown layer remaining is slowly poured over a mixture of crushed ice and 400 ml of concentrated HCl. This results in decomposition of the dark material with violent fuming, and yellow precipitate formation. The resulting precipitate is filtered then washed with H2O, a small volume of EtOH, and ether. The remaining solid is crystallized from large volumes of CH2Cl2 containing a small amount of MeOH to aid in solubility which yielded 3 crops of the title compound, m.p. 186°-188° C.; [according to the literature, R. H. Uloth, et al., J. Med. Chem. 9, p. 88 (1966), m.p. 190°-191° C. dec⟧ resulting in a deep red color and separation of the reaction mixture into two layers the addition is then heated to reflux After refluxing for 1 hour the oil bath is removed the reaction is stirred at room temperature overnight to separate the upper layer is decanted The viscous dark brown layer remaining is slowly poured over a mixture of crushed ice and 400 ml of concentrated HCl This results in decomposition of the dark material with violent fuming, and yellow precipitate formation The resulting precipitate is filtered then washed with H2O The remaining solid is crystallized from large volumes of CH2Cl2 containing a small amount of MeOH

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

Procedure: A mechanically stirred suspension of aluminum chloride (88.0 g, 0.66 moles) and 150 ml of carbon disulfide under N2 is cooled in an ice bath. Methanesulfonanilide as prepared in Preparation 1 (30.0 g, 0.175 mol) and succinic anhydride (17.5 g, 0.175 mol) are combined and added rapidly to the cooled reaction mixture. The ice bath is removed and the mixture is stirred at ambient temperature for 6 hours. The reaction mixture is then heated to 55° C. and allowed to continue for 18 hours. The reaction mixture is separated into two layers the bottom of which solidifies. The upper layer is decanted and the remaining solid layer is decomposed with ice. The resulting suspension is filtered and the solid is washed several times with methylene chloride and dissolved in a mixture of saturated sodium bicarbonate (500 ml) and water (500 ml). This solution is acidified (pH2) with HCl and the resulting precipitate is collected by filtration, redissolved in NaHCO3 and reprecipitated with HCl. The solid, 4-[(methylsulfonyl)amino]-γ-oxobenzenebutanoic acid, is collected by filtration and dried to give the title compound with mp 198°-200° C. is cooled in an ice bath added rapidly to the cooled reaction mixture The ice bath is removed The reaction mixture is then heated to 55° C. to continue for 18 hours The reaction mixture is separated into two layers the bottom of which The upper layer is decanted The resulting suspension is filtered the solid is washed several times with methylene chloride dissolved in a mixture of saturated sodium bicarbonate (500 ml) and water (500 ml) the resulting precipitate is collected by filtration redissolved in NaHCO3 reprecipitated with HCl The solid, 4-[(methylsulfonyl)amino]-γ-oxobenzenebutanoic acid, is collected by filtration dried

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

Procedure: A mechanically stirred solution of aniline (139.7 g, 1.5 mole) in pyridine (2 liters), under N2 is cooled in an icebath. Methanesulfonyl chloride (171.8 g, 1.5 mole) is added dropwise to this solution while the temperature is maintained at 15°-20° C., which results in a red-orange color change in the reaction mixture. After the addition is complete the ice bath is removed and the reaction is allowed to continue at ambient temperature. By TLC on silica gel (2.5% MeOH:CH2Cl2) the reaction is complete after 21/2 hours. The reaction mixture is concentrated in vacuo and the residue is combined with 700 ml of water which results in crystallization of a dark red material. This material is filtered and washed several times with water. The filtered material is dissolved in CH2Cl2, washed with brine, dried (Na2SO4), and concentrated in vacuo. The residue is dissolved in hot ethyl acetate, treated with Darco (decolorizing carbon) and crystallized to yield four crops of methanesulfonanilide 157.37 g, 19.27 g, 26.55 g, 5.07 g which had a mp: 93°-94° C. is maintained at 15°-20° C. which results in a red-orange color change in the reaction mixture After the addition is removed to continue at ambient temperature 2 hours The reaction mixture is concentrated in vacuo results in crystallization of a dark red material This material is filtered washed several times with water The filtered material is dissolved in CH2Cl2 washed with brine dried (Na2SO4) concentrated in vacuo The residue is dissolved in hot ethyl acetate treated with Darco (decolorizing carbon) crystallized

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

Procedure: A mechanically stirred solution of aniline (139.7 g, 1.5 mole) in pyridine (2 liters), under N2 is cooled in an icebath. Methanesulfonyl chloride (171.8 g, 1.5 mole) is added dropwise to this solution while the temperature is maintained at 15°-20° C., which results in a red-orange color change in the reaction mixture. After the addition is complete the ice bath is removed and the reaction is allowed to continue at ambient temperature. By TLC on silica gel (2.5% MeOH:CH2Cl2) the reaction is complete after 21/2 hours. The reaction mixture is concentrated in vacuo and the residue is combined with 700 ml of water which results in crystallization of a dark red material. This material is filtered and washed several times with water. The filtered material is dissolved in CH2Cl2, washed with brine, dried (Na2SO4), and concentrated in vacuo. The residue is dissolved in hot ethyl acetate, treated with Darco (decolorizing carbon) and crystallized to yield four crops of methanesulfonanilide 157.37 g, 19.27 g, 26.55 g, 5.07 g which had a mp: 93°-94° C. is maintained at 15°-20° C. which results in a red-orange color change in the reaction mixture After the addition is removed to continue at ambient temperature 2 hours The reaction mixture is concentrated in vacuo results in crystallization of a dark red material This material is filtered washed several times with water The filtered material is dissolved in CH2Cl2 washed with brine dried (Na2SO4) concentrated in vacuo The residue is dissolved in hot ethyl acetate treated with Darco (decolorizing carbon) crystallized

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a flask containing 128.4 g (0.75 mole) of N-phenylmethanesulfonamide, 169.5 g (1.50 mole) of chloroacetyl chloride in 1 L of methylene chloride under an atmosphere of nitrogen and cooled to about -10° C. add 300 g (2.25 mole) of aluminum chloride. Stir the resulting mixture for about 2 hours at -10° C. then warm to room temperature for about 16 hours. Pour the reaction mixture onto 2 Kg of ice containing 600 mL of concentrated hydrochloric acid. Collect the precipitate and wash with methanol (3×300 mL) and dry in vacuo to give the title compound. then warm to room temperature for about 16 hours Collect the precipitate wash with methanol (3×300 mL) dry in vacuo

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

Procedure: To a 0° C. solution of 250 g (2.68 mole) of aniline and 233.2 g (2.95 mole) of pyridine in 1.25 L of methylene chloride and 319.6 g (2.79 mole) of methanesulfonyl chloride dropwise. Stir the resulting solution at 0° C. for about 30 minutes then warm to ambient temperature for about 16 hours. Extract the mixture with 2N aqueous sodium hydroxide (4×1 L). Combine the aqueous extracts and wash with 1 L of methylene chloride. Cool the aqueous layer to about 0° C. and acidify with concentrated hydrochloric acid until about pH 1. Collect the precipitate and dry to give the title compound. To a 0° C. then warm to ambient temperature for about 16 hours Extract the mixture with 2N aqueous sodium hydroxide (4×1 L) Combine the aqueous extracts and wash with 1 L of methylene chloride Cool the aqueous layer to about 0° C. Collect the precipitate dry