(2-carbonochloridoylphenyl) acetate

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: 2,5-Dimethoxyaniline (10.0 g, 65.3 mmol) was dissolved in pyridine (100 ml), and a solution of O-acetylsalicyloyl chloride (13.0 g, 65.3 mmol) in ethyl acetate (50 ml) was added thereto over 15 minutes under ice cooling. Thereafter, the mixture was stirred for 15 minutes at the same temperature as above. After adding water (10 ml) to the reaction mixture to stop the reaction, ethyl acetate (500 ml) was added and the reaction mixture was washed with 3 N hydrochloric acid (500 ml), water (500 ml), 2% sodium hydrogen carbonate solution (500 ml), and water (500 ml) in order. After drying it over Glauber's salt, the ethyl acetate layer was concentrated under reduced pressure and dried under vacuum to obtain the titled compound (19.8 g) as pale yellow syrup. The compound was used in the subsequent step without purification. The titled compound purified by preparative thin layer chromatography had the following physical properties. was added the reaction mixture was washed with 3 N hydrochloric acid (500 ml), water (500 ml), 2% sodium hydrogen carbonate solution (500 ml), and water (500 ml) in order After drying it over Glauber's salt the ethyl acetate layer was concentrated under reduced pressure dried under vacuum

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

Procedure: 2-Acetylbenzoic acid azide was prepared by reacting 2-acetoxybenzoyl chloride with sodium azide in acetone and water at 0-5° C. for 24 hours. It had an IR peak at 2245 cm−1 (azide). The crude azide was then heated in benzene at 70-75° C. under nitrogen for 2 hours to give 2-acetoxyphenylisocyanate. at 0-5° C. for 24 hours

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

Procedure: Acetylsalicylic acid (1.39g.) was converted to its acid chloride by conventional method using thionyl chloride and put in solution in acetone (25 ml.). 2-Methyl-4-amino-6-chlorophenol (1.35 g.) and N,N-dimethylaniline (about 1 ml.) were dissolved in acetone to which, with stirring in the cold at 1° to 2° C., the above-prepared acetone solution of acetylsalicyloyl chloride was added dropwise over 20-30 minutes, and reaction was continued for 1-2 hours. Then under reduced pressure the acetone was evaporated off, and the residue was put in solution in 2 N sodium hydroxide by stirring several hours at room temperature. Addition of 2 N hydrochloric acid to make the pH of the solution lower than 1 resulted in the formation of a precipitate which was recrystallized from aqueous acetone to give white crystals (1.08 g.) of 5-chloro-2',4-dihydroxy-3-methylbenzanilide. Yield: 45.4%. Melting point: 192°-194° C. reaction Then under reduced pressure the acetone was evaporated off by stirring several hours at room temperature Addition of 2 N hydrochloric acid resulted in the formation of a precipitate which was recrystallized from aqueous acetone

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

Procedure: Acetylsalicylic acid (1.8 g.) was converted to its acid chloride by conventional method using thionyl chloride and dissolved in acetone (30 ml.). 4-Amino-2,6-dichloroanisole (2.13 g.) with N,N-dimethylaniline (1.27 ml.) was dissolved in acetone (25 ml.) to which, with stirring in the cold at 0°-10° C., the above acetone solution of acetylsalicyloyl chloride was added dropwise over 20-30 minutes. Reaction continued for 1-2 hours, then the solution was evaporated to dryness under reduced pressure, the residue being put in sodium hydroxide solution and gently agitated for 1-2 hours for cleavage of the acetyl group. After reaction was complete the solution was made acidic by the addition of 2 N hydrochloric acid and the precipitate which formed was collected by filtration and recrystallized from aqueous acetone to give needle-like crystals (2.0 g.) of 3,5-dichloro-2'-hydroxy-4-methoxybenzanilide. Yield 64%. The melting point of the product is 226° - 228° C. Reaction the solution was evaporated to dryness under reduced pressure gently agitated for 1-2 hours for cleavage of the acetyl group After reaction the precipitate which formed was collected by filtration recrystallized from aqueous acetone

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

Procedure: 3-Bromo-5-aminosalicylic acid (0.73 g.) was dissolved in acetone (30 ml.) and pyridine (0.4 ml.) to which an acetone (14 ml.) solution containing acetyl-salicyloyl chloride (prepared from 0.53 g. of acetyl-salicylic acid) was added dropwise with stirring. After reaction the solution was evaporated to dryness under reduced pressure and the residue was dissolved in ethyl acetate. After washing the solution with water and 1 N hydrochloric acid successively, the ethyl acetate was evaporated off under reduced pressure, yielding a residue which was redissolved in a mixture of methanol and 2 N sodium hydroxide (14 ml. each). After stirring the solution for several hours and then acidifying with 2 N hydrochloric acid solution, a precipitate was formed, collected and crystallized from aqueous methanol to give light brown crystals (0.90 g.) of 5-bromo-3-carboxy-2',4-dihydroxybenzanilide. was added dropwise After reaction the solution was evaporated to dryness under reduced pressure the residue was dissolved in ethyl acetate After washing the solution with water and 1 N hydrochloric acid successively the ethyl acetate was evaporated off under reduced pressure yielding a residue which After stirring the solution for several hours a precipitate was formed collected crystallized from aqueous methanol

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

Procedure: 2,6-Dibromo-4-aminophenol (0.6 g.) was dissolved in acetone (30 ml.) to which was added pyridine (0.32 ml.). Then dropwise and with stirring the solution was added to an acetone solution (10 ml.) containing acetylsalicyloyl chloride which was prepared from acetylsalicylic acid (0.38 g.). Then the reactant solution was evaporated to dryness under reduced pressure to give a residue which was dissolved in ethyl acetate. After washing first with water and then with 1 N hydrochloric acid, the solution was evaporated under reduced pressure to remove ethyl acetate. The residues were redissolved in a mixture of methanol and 2 N sodium hydroxide (10 ml. each). Stirring this solution for several hours and acidifying with 2 N hydrochloric acid precipitated the product which was recrystallized from aqueous methanol to give light brown crystals of 3,5-dibromo-2',4-dihydroxybenzanilide (0.88 g.). Yield: 78%. The compound melts at 182°-187° C. Then the reactant solution was evaporated to dryness under reduced pressure to give a residue which After washing first with water with 1 N hydrochloric acid, the solution was evaporated under reduced pressure to remove ethyl acetate The residues were redissolved in a mixture of methanol and 2 N sodium hydroxide (10 ml Stirring this solution for several hours precipitated the product which was recrystallized from aqueous methanol