2-amino-1-(2,3-dichlorophenyl)ethanone;hydrochloride

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 10.7 g of 2,3-dichlorophenacylamine hydrochloride and 6 g of methyl 3-dimethylaminoacrylate are heated for 2 hours under reflux in 120 ml of ethanol. Then a solution of 4 g of sodium ethylate in 40 ml of ethanol is added dropwise and the reaction mixture is heated for another hour under reflux. The reaction mixture is then concentrated by evaporation and the oily residue is purified by column chromatography (silica gel; elution with a 3:1 mixture of toluene/ethyl acetate. Melting point: 205°-206° C. the reaction mixture is heated for another hour under reflux The reaction mixture is then concentrated by evaporation the oily residue is purified by column chromatography (silica gel elution with a 3:1 mixture of toluene/ethyl acetate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 10.7 g of 2,3-dichlorophenacylamine hydrochloride and 6 g of methyl 3-dimethylaminoacrylate are heated for 2 hours under reflux in 120 ml of ethanol. Then a solution of 4 g of sodium ethylate in 40 ml of ethanol is added dropwise and the reaction mixture is heated for another hour under reflux. The reaction mixture is then concentrated by evaporation and the oily residue is purified by column chromatography (silica gel; elution with a 3:1 mixture of toluene/ethyl acetate. Melting point: 205°-206° C. the reaction mixture is heated for another hour under reflux The reaction mixture is then concentrated by evaporation the oily residue is purified by column chromatography (silica gel elution with a 3:1 mixture of toluene/ethyl acetate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2 g of 2,3-dichlorophenacylamine hydrochloride, 1 g of 3-hydroxyacrylonitrile, sodium salt, and 20 ml of ethanol are heated for 2 hours under reflux. The reaction mixture is concentrated by evaporation and the oily residue is purified by column chromatography (silica gel; elution with a 4:1 mixture of toluene/ethyl acetate), affording 3-(2,3-dichlorophenacylamino)acrylonitrile in the cis/trans ratio of 5:1. Melting point: 122°-125° C. under reflux The reaction mixture is concentrated by evaporation the oily residue is purified by column chromatography (silica gel elution with a 4:1 mixture of toluene/ethyl acetate),

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2 g of 2,3-dichlorophenacylamine hydrochloride, 1 g of 3-hydroxyacrylonitrile, sodium salt, and 20 ml of ethanol are heated for 2 hours under reflux. The reaction mixture is concentrated by evaporation and the oily residue is purified by column chromatography (silica gel; elution with a 4:1 mixture of toluene/ethyl acetate), affording 3-(2,3-dichlorophenacylamino)acrylonitrile in the cis/trans ratio of 5:1. Melting point: 122°-125° C. under reflux The reaction mixture is concentrated by evaporation the oily residue is purified by column chromatography (silica gel elution with a 4:1 mixture of toluene/ethyl acetate),

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 20.0 g of 2,3-dichlorophenacylamine hydrochloride and 10.0 g of 3-dimethylaminoacrylonitrile are heated for 1 hour under reflux in 300 ml of ethanol. Then an ethanolic solution of sodium ethylate, prepared from 2.1 g of sodium and 30 ml of ethanol, is rapidly added dropwise and the reaction mixture is stirred for another 10 minutes under reflux. The reaction mixture is cooled to room temperature and then poured into ice/hydrochloric acid and the resultant mixture is stirred for 11/2 hours. The precipitate is isolated by filtration, washed with water and dried, affording 15.4 g (78% of theory) of title compound with a melting point of 152°-154° C. is rapidly added dropwise under reflux The precipitate is isolated by filtration washed with water dried

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 20.0 g of 2,3-dichlorophenacylamine hydrochloride and 10.0 g of 3-dimethylaminoacrylonitrile are heated for 1 hour under reflux in 300 ml of ethanol. Then an ethanolic solution of sodium ethylate, prepared from 2.1 g of sodium and 30 ml of ethanol, is rapidly added dropwise and the reaction mixture is stirred for another 10 minutes under reflux. The reaction mixture is cooled to room temperature and then poured into ice/hydrochloric acid and the resultant mixture is stirred for 11/2 hours. The precipitate is isolated by filtration, washed with water and dried, affording 15.4 g (78% of theory) of title compound with a melting point of 152°-154° C. is rapidly added dropwise under reflux The precipitate is isolated by filtration washed with water dried

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 50.0 g of the N-acetyl-2,3-dichlorophenacylamine obtained in (a) are heated for 2 hours under reflux in 500 ml of hydrochloric acid. The slightly turbid reaction solution is concentrated by evaporation and the residue is digested with ethyl acetate. The crystalline 2,3-dichlorophenacylamine hydrochloride is isolated by filtration and dried. Melting point: 217°-218° C. IR (solid/KBr) in cm-1 : 1695 (CO). (Another crystal modification shows two carbonyl resonance bands at 1690 and 1705 cm-1). 1H-NMR (DMSO, d6) in ppm: 4.54 (s, 2H); 7.6 (t,1H); 7.9 (m, 2H); 8.6 (s, 3H, replaceable with D2O). are heated for 2 hours The slightly turbid reaction solution is concentrated by evaporation

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 50.0 g of the N-acetyl-2,3-dichlorophenacylamine obtained in (a) are heated for 2 hours under reflux in 500 ml of hydrochloric acid. The slightly turbid reaction solution is concentrated by evaporation and the residue is digested with ethyl acetate. The crystalline 2,3-dichlorophenacylamine hydrochloride is isolated by filtration and dried. Melting point: 217°-218° C. IR (solid/KBr) in cm-1 : 1695 (CO). (Another crystal modification shows two carbonyl resonance bands at 1690 and 1705 cm-1). 1H-NMR (DMSO, d6) in ppm: 4.54 (s, 2H); 7.6 (t,1H); 7.9 (m, 2H); 8.6 (s, 3H, replaceable with D2O). are heated for 2 hours The slightly turbid reaction solution is concentrated by evaporation

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Under argon, 300 mg (1.25 mmol) of the compound of Example 41A were initially charged in 2 ml of methanol. 189 mg (5.0 mmol) of sodium borohydride were added and the mixture was stirred overnight. 1 N hydrochloric acid was added slowly until the evolution of gas had ceased, and the methanol was then removed on a rotary evaporator. The aqueous residue was made alkaline by addition of sodium bicarbonate solution and extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulphate and freed from the solvent on a rotary evaporator. The residue (189 mg, 74% of theory) corresponded to the title compound. the methanol was then removed on a rotary evaporator by addition of sodium bicarbonate solution extracted three times with ethyl acetate The combined organic phases were dried over sodium sulphate freed from the solvent on a rotary evaporator

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Under argon, 300 mg (1.25 mmol) of the compound of Example 41A were initially charged in 2 ml of methanol. 189 mg (5.0 mmol) of sodium borohydride were added and the mixture was stirred overnight. 1 N hydrochloric acid was added slowly until the evolution of gas had ceased, and the methanol was then removed on a rotary evaporator. The aqueous residue was made alkaline by addition of sodium bicarbonate solution and extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulphate and freed from the solvent on a rotary evaporator. The residue (189 mg, 74% of theory) corresponded to the title compound. the methanol was then removed on a rotary evaporator by addition of sodium bicarbonate solution extracted three times with ethyl acetate The combined organic phases were dried over sodium sulphate freed from the solvent on a rotary evaporator

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: At RT, 411 mg (4.33 mmol) of sodium diformylamide were added to 1.0 g (3.73 mmol) of 2-bromo-1-(2,3-dichlorophenyl)ethanone [for the preparation, see for example U.S. Pat. No. 5,831,132] in 4 ml of acetonitrile, and the mixture was stirred at RT overnight. The mixture was then heated to 70° C. and filtered whilst still warm. The solid that remained was washed with 2 ml of hot acetonitrile. The combined filtrates were freed from the solvent on a rotary evaporator. 10 ml of a 5% strength ethanolic hydrogen chloride solution were added to the dark-brown oily residue, and the mixture was stirred at RT overnight. The volatile components were removed on a rotary evaporator and the yellow solid that remained was stirred in 20 ml of boiling diethyl ether. After cooling to RT, the solid was isolated by filtration, washed with diethyl ether and dried under high vacuum. This gave 410 mg (46% of theory) of the title compound. for the preparation filtered whilst still warm The solid that remained was washed with 2 ml of hot acetonitrile The combined filtrates were freed from the solvent on a rotary evaporator 10 ml of a 5% strength ethanolic hydrogen chloride solution were added to the dark-brown oily residue The volatile components were removed on a rotary evaporator the yellow solid that remained was stirred in 20 ml of boiling diethyl ether After cooling to RT the solid was isolated by filtration washed with diethyl ether dried under high vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 5.4 g of 3-dimethylaminoacrolein, 3.2 g of 2,3-dichlorophenacylamine hydrochloride and 60 ml of ethanol are heated for 11/2 hours under reflux. Then a solution of sodium ethylate in ethanol (prepared from 1 g of sodium and 15 ml of ethanol) is added dropwise and the reaction mixture is heated under reflux for another 30 minutes. After it has cooled to room temperature, the reaction mixture is poured onto ice/water and neutralised with hydrochloric acid. The precipitate is washed with water, dried in vacuo, and the dry residue is purified by column chromatography (silica gel; elution with a 4:1 mixture of toluene/ethyl acetate). M.p. 152°-154° C. IR (solid/KBr) in cm-1 : 1655 (CO). 1H-NMR (CDCl3) in ppm: 7.0 (broad s, 1H); 7.3 (m, 2H); 9.66 (s, 1H); 11.9 (s, 1H, H replaceable with D2O). Mass peak at 204. This substance is novel, has fungicidal activity, and falls within the ambit of the invention. under reflux the reaction mixture is heated under reflux for another 30 minutes The precipitate is washed with water dried in vacuo the dry residue is purified by column chromatography (silica gel elution with a 4:1 mixture of toluene/ethyl acetate)