4-chlorobenzoyl cyanide

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A solution of 1.65 g (0.01 mole) of p-chlorobenzoylcyanide, 1.81 g (0.01 mole) of ethyl 1,4-dimethylpyrrole-2-acetate and 0.08 g of anhydrous oxalic acid in 4 ml of ether was stored in the dark under nitrogen for four days. The solution was diluted with CH2Cl2. The organic solution was washed with 10 percent NaOH solution, dried (MgSO4), and the solvent evaporated in vacuo. The residue was recrystallized from 1,1,1-trichloroethane to give 1.04 g of ethyl 5-(4-chlorobenzoyl)-1,4-dimethylpyrrole-2-acetate, mp 105°-108° C., undepressed by admixture with authentic material. for four days The organic solution was washed with 10 percent NaOH solution dried (MgSO4) the solvent evaporated in vacuo The residue was recrystallized from 1,1,1-trichloroethane

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

実験手順: A solution of 1.65 g (0.01 mole) of p-chlorobenzoylcyanide, 1.81 g (0.01 mole) of ethyl 1,4-dimethylpyrrole-2-acetate and 0.08 g of anhydrous oxalic acid in 4 ml of ether was stored in the dark under nitrogen for four days. The solution was diluted with CH2Cl2. The organic solution was washed with 10 percent NaOH solution, dried (MgSO4), and the solvent evaporated in vacuo. The residue was recrystallized from 1,1,1-trichloroethane to give 1.04 g of ethyl 5-(4-chlorobenzoyl)-1,4-dimethylpyrrole-2-acetate, mp 105°-108° C., undepressed by admixture with authentic material. for four days The organic solution was washed with 10 percent NaOH solution dried (MgSO4) the solvent evaporated in vacuo The residue was recrystallized from 1,1,1-trichloroethane

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 1.26 g (8.37 mmol) 4-chloro-benzoylcyanide was added bis-(2-chloroethyl)-carbamic acid tert-butyl ester (2.02 g, 8.37 mmol) in 25 ml N,N-dimethylformamide. The resulting mixture was stirred and cooled in an ice bath, then sodium hydride (60% suspension in mineral oil) (1.1 g, 42 mmol) was added portionwise. The reaction was brought to room temperature and then heated in an oil bath at 60° C. for 16 hours. The reaction mixture was quenched by addition of ice water and the aqueous phase was extracted with ethyl acetate. The combined organic layers were washed twice with water, once with brine, dried with magnesium sulfate and concentrated in vacuo. The residual brown oil was purified by silica gel chromatography eluting with hexane-ethyl:acetate (9:1) to give the title compound (1.44 g, 54%). cooled in an ice bath was brought to room temperature The reaction mixture was quenched by addition of ice water the aqueous phase was extracted with ethyl acetate The combined organic layers were washed twice with water, once with brine dried with magnesium sulfate concentrated in vacuo The residual brown oil was purified by silica gel chromatography eluting with hexane-ethyl:acetate (9:1)

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 1.26 g (8.37 mmol) 4-chloro-benzoylcyanide was added bis-(2-chloroethyl)-carbamic acid tert-butyl ester (2.02 g, 8.37 mmol) in 25 ml N,N-dimethylformamide. The resulting mixture was stirred and cooled in an ice bath, then sodium hydride (60% suspension in mineral oil) (1.1 g, 42 mmol) was added portionwise. The reaction was brought to room temperature and then heated in an oil bath at 60° C. for 16 hours. The reaction mixture was quenched by addition of ice water and the aqueous phase was extracted with ethyl acetate. The combined organic layers were washed twice with water, once with brine, dried with magnesium sulfate and concentrated in vacuo. The residual brown oil was purified by silica gel chromatography eluting with hexane-ethyl:acetate (9:1) to give the title compound (1.44 g, 54%). cooled in an ice bath was brought to room temperature The reaction mixture was quenched by addition of ice water the aqueous phase was extracted with ethyl acetate The combined organic layers were washed twice with water, once with brine dried with magnesium sulfate concentrated in vacuo The residual brown oil was purified by silica gel chromatography eluting with hexane-ethyl:acetate (9:1)

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

実験手順: The process of claim 1, wherein 4-chlorobenzoylcyanide is reacted with ethyl 1,4-dimethylpyrrole-2-acetate to produce ethyl 5-(4-chlorobenzoyl)-1,4-dimethyl-pyrrole-2-acetate.

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

実験手順: A 1.50 g (0.0090 mole) sample of 4-chlorobenzoylcyanide was added over a one-hour period to 1.50 g (0.0082 mole) of ethyl 1,4-dimethylpyrrole-2-acetate at 120°-130° through which nitrogen was slowly bubbled. The mixture was heated for 27 hours. The resulting oil was chromatographed on silica gel with successive elution with hexane and 1,1,1-trichloroethane. The solvent was evaporated in vacuo from compound-bearing fractions. The residue was chromatographed through a Waters Associates, Prep LC, System 500 with elution with a 2:3 mixture of hexane:1,1,1-trichloroethane. Evaporation of solvent from the second compound-bearing fraction afforded solid which was recrystallized from methanol to give 0.74 g (28 percent yield) of ethyl 5-(4-chlorobenzoyl)-1,4-dimethylpyrrole-2-acetate, mp 108°-109°, undepressed by admixture with authentic material. was slowly bubbled The mixture was heated for 27 hours The resulting oil was chromatographed on silica gel with successive elution with hexane and 1,1,1-trichloroethane The solvent was evaporated in vacuo from compound-bearing fractions The residue was chromatographed through a Waters Associates, Prep LC, System 500 with elution with a 2:3 mixture of hexane Evaporation of solvent from the second compound-bearing fraction afforded solid which was recrystallized from methanol

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: The process of claim 1, wherein 4-chlorobenzoylcyanide is reacted with ethyl 1,4-dimethylpyrrole-2-acetate to produce ethyl 5-(4-chlorobenzoyl)-1,4-dimethyl-pyrrole-2-acetate.

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

実験手順: A 1.50 g (0.0090 mole) sample of 4-chlorobenzoylcyanide was added over a one-hour period to 1.50 g (0.0082 mole) of ethyl 1,4-dimethylpyrrole-2-acetate at 120°-130° through which nitrogen was slowly bubbled. The mixture was heated for 27 hours. The resulting oil was chromatographed on silica gel with successive elution with hexane and 1,1,1-trichloroethane. The solvent was evaporated in vacuo from compound-bearing fractions. The residue was chromatographed through a Waters Associates, Prep LC, System 500 with elution with a 2:3 mixture of hexane:1,1,1-trichloroethane. Evaporation of solvent from the second compound-bearing fraction afforded solid which was recrystallized from methanol to give 0.74 g (28 percent yield) of ethyl 5-(4-chlorobenzoyl)-1,4-dimethylpyrrole-2-acetate, mp 108°-109°, undepressed by admixture with authentic material. was slowly bubbled The mixture was heated for 27 hours The resulting oil was chromatographed on silica gel with successive elution with hexane and 1,1,1-trichloroethane The solvent was evaporated in vacuo from compound-bearing fractions The residue was chromatographed through a Waters Associates, Prep LC, System 500 with elution with a 2:3 mixture of hexane Evaporation of solvent from the second compound-bearing fraction afforded solid which was recrystallized from methanol

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

実験手順: The title compound was prepared as in Example 2(a) from 4-chlorobenzoyl cyanide amidinohydrazone obtained in Example 7. The solvent for the ring closure was a mixture of 1-propanol and dimethyl sulfoxide (4:1). Total yield (from 4-chlorobenzoyl cyanide): 72%; m.p. 219-221° C. (uncorrected).

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

実験手順: 4-Chlorobenzoyl cyanide (13.0 g, 0.079 mol) prepared in Example 1a was added to a stirred mixture of sodium bromide (1.0 g, 0.01 mol) and 80% sulphuric acid (10 ml). An exothermic reaction took place with the formation of a solid yellow mass. Ethanol (50 ml) was added and the mixture was heated under reflux to give a yellow solution. On cooling, a colourless precipitate formed. The mixture was diluted with cold water and extracted with isopropyl ether. The organic extract was washed with water, sodium bicarbonate solution and then again with water and dried over sodium sulphate. Evaporation and distillation of the solution gave the product as a yellow oil (8.2 g, 54%)--b.p. 82°-84° C./0.05 mm Hg. An exothermic reaction the mixture was heated under reflux to give a yellow solution On cooling a colourless precipitate formed extracted with isopropyl ether The organic extract was washed with water, sodium bicarbonate solution again with water and dried over sodium sulphate Evaporation and distillation of the solution