4-aminobenzaldehyde

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: 172 mg (1.60 mmol) of 4-toluidine were reacted analogously to Example 1 in the presence of 32.1 mg (0.180 mmol) of 3-amino-N-hydroxyphthalimide. After a reaction time of 22 hours, the reaction solution was brought to pH 8 with 2M NaOH, extracted with chloroform and examined by NMR spectroscopy. Yield 62% of 4-aminobenzaldehyde. After a reaction time of 22 hours extracted with chloroform

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

Procedure: 172 mg (1.60 mmol) of 4-toluidine were reacted analogously to Example 1 in the presence of 32.1 mg (0.180 mmol) of 3-amino-N-hydroxyphthalimide. After a reaction time of 22 hours, the reaction solution was brought to pH 8 with 2M NaOH, extracted with chloroform and examined by NMR spectroscopy. Yield 62% of 4-aminobenzaldehyde. After a reaction time of 22 hours extracted with chloroform

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

Procedure: 36.3 g (0.3 mol) of p-aminobenzaldehyde are suspended in 450 ml of isopropanol. A mixture of 59.1 g (0.3 mol) of 2-ethylhexyl cyanoacetate and of catalyst (0.375 ml of diethylamine and 1.125 ml of acetic acid) is introduced therein. The mixture is refluxed for 5 hours. The same amount of catalyst is added again and refluxing is continued for a further 4 hours. The insoluble materials are removed by hot filtration and the mixture is concentrated to a volume of 300 ml and left to crystalize. After filtration and drying, 59.6 g (66% yield) of an orange-coloured powder are obtained, and are used without further purification for the following step. The mixture is refluxed for 5 hours The same amount of catalyst is added again refluxing The insoluble materials are removed by hot filtration the mixture is concentrated to a volume of 300 ml left to crystalize After filtration drying

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

Procedure: 36 g (0.3 mol) of para-aminobenzaldehyde are suspended in 300 ml of ethanol. 33.9 g (0.3 mol) of ethyl cyanoacetate and a mixture of 0.375 ml of diethylamine and 1.125 ml of acetic acid, as catalyst, are added to the suspension. The reaction mixture is refluxed for 2 hours, left to cool and then crystallized. After separating out the crystals by filtration and drying, 53.9 g (83% yield) of ethyl 3-(4-aminophenyl)-2-cyanoacrylate are obtained in the form of orange-coloured crystals. as catalyst, are added to the suspension The reaction mixture is refluxed for 2 hours left to cool crystallized After separating out the crystals by filtration drying

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

Procedure: To a solution of 4-aminobenzaldehyde (1 g, 8.52 mmol) at 0° C. under nitrogen atmosphere were added triethylamine (2.3 mL, 16.5 mmol), 4-dimethylaminopyridine (0.1 g, 0.82 mmol) and acetoxyacetyl chloride (1.77 mL, 16.5 mmol). The reaction mixture was allowed to warm up to room temperature and was stirred for 2.5 h. Triethylamine (1.15 mL, 8.25 mmol) and acetoxyacetyl chloride (0.88 mL, 8.25 mmol) were added and the reaction mixture was stirred for 1 h more. The reaction mixture was poured into a 1 M hydrochloric acid solution (60 mL), then extracted with methylene chloride (20 mL×3) and the combined organic layers were washed with saturated aqueous sodium bicarbonate solution and dried over anhydrous sodium sulfate. The crude solid (3.17 g) was purified by flash column chromatography to provide pure acetic acid (4-formyl-phenylcarbamoyl)-methyl ester (1.14 g, 62% yield) as an orange solid. A mixture of 2-amino-4,6-dimethoxy-benzamide (0.15 g, 0.76 mmol), Acetic acid (4-formyl-phenylcarbamoyl)-methyl ester (0.169 g, 0.76 mmol), sodium hydrogensulfite (0.087 g, 0.84 mmol) and p-toluenesulfonic acid (15 mg, 0.076 mmol) in N,N-dimethyl acetamide (5 mL) was stirred at 150° C. for 4.5 h under nitrogen. The reaction mixture was cooled to room temperature and diluted with cold water (60 mL) to obtain a yellow solid. The yellow solid was filtered off, washed with cold water (20 mL×2), methanol and dried under vacuum to provide crude compound (230 mg, 75%). the reaction mixture was stirred for 1 h more extracted with methylene chloride (20 mL×3) the combined organic layers were washed with saturated aqueous sodium bicarbonate solution dried over anhydrous sodium sulfate The crude solid (3.17 g) was purified by flash column chromatography

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

Procedure: 2-(3-Nitro-phenyl)-1H-benzoimidazole-5-carboxylic acid amide. To a flask containing crude 4-amino-benzaldehyde (100 mg, 0.82 mmol), pyridine (0.15 mL, 1.87 mmol) and CH2Cl2 (4 mL), was added 3,4-dichlorobenzenesulfonyl chloride (184 mg, 0.75 mmol). The mixture was stirred for 16 h at room temperature, and was then cooled and concentrated. The crude product was purified by silica gel flash chromatography (eluted with 5% methanol/CH2Cl2) to provide 179 mg (72%) of 3,4-dichloro-N-(4-formyl-phenyl)-benzenesulfonamide. was then cooled concentrated The crude product was purified by silica gel flash chromatography (eluted with 5% methanol/CH2Cl2)

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

Procedure: 2-(3-Nitro-phenyl)-1H-benzoimidazole-5-carboxylic acid amide. To a flask containing crude 4-amino-benzaldehyde (100 mg, 0.82 mmol), pyridine (0.15 mL, 1.87 mmol) and CH2Cl2 (4 mL), was added 3,4-dichlorobenzenesulfonyl chloride (184 mg, 0.75 mmol). The mixture was stirred for 16 h at room temperature, and was then cooled and concentrated. The crude product was purified by silica gel flash chromatography (eluted with 5% methanol/CH2Cl2) to provide 179 mg (72%) of 3,4-dichloro-N-(4-formyl-phenyl)-benzenesulfonamide. was then cooled concentrated The crude product was purified by silica gel flash chromatography (eluted with 5% methanol/CH2Cl2)