1H-pyrrole-2-carbonitrile

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

Procedure: Trichloracetyl chloride (44.4 g, 27.3 mL, 244 mmol) in dichloromethane (75 mL) was added over 20 min to a mechanically stirred suspension of aluminum trichloride (54.3 g, 407 mmol) in dichloromethane (150 mL). The resulting mixture was stirred for 30 min, and then 2-cyanopyrrole (15.0 g, 163 mmol) in dichloromethane (75 mL) was added over 30 min. The reaction was heated at reflux for 5 h and then allowed to cool. The reaction was diluted with ethyl acetate (600 mL) and then quenched slowly with water (300 mL). The layers were separated and then the organic layer was washed with water and brine, dried (magnesium sulfate) and evaporated under reduced pressure to afford a quantitative yield of desired product (39.0 g, 100%) containing trace impurities. This material was used in the next step without further purification. 1H NMR (DMSO-d6) δ 8.14 (s, 1H), 7.55 (s, 1H). The reaction was heated at reflux for 5 h to cool quenched slowly with water (300 mL) The layers were separated the organic layer was washed with water and brine dried (magnesium sulfate) evaporated under reduced pressure

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

Procedure: A solution of 1H-pyrrole-2-carbonitrile 10 g (108 mM) and sodium methoxide (1 eq) in ethanol (20 ml) and stirred for 10 min. Hydrazine hydrate (3 eq.) is then added and resulting reaction mixture is stirred at room temperature for 18 hrs. Reaction mass is then diluted with water, extracted with ethyl acetate, dried over anhydrous sodium sulphate and concentrated under vacuum to yield desired compound. resulting reaction mixture Reaction mass extracted with ethyl acetate dried over anhydrous sodium sulphate concentrated under vacuum

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

Procedure: A mixture of methyl thiosalicylate (2.00 g, 11.8 mmol), pyrrole-2-carbonitrile (1.10 g, 11.9 mmol), triethylamine (2.00 ml, 14.3 mmol) and toluene (4.0 ml) was refluxed for 15 hrs as described in Example 1. After cooling, the precipitated crystals were collected by filtration and recrystallized from hexane-ethanol to give the titled compound (1.90 g, 73%). was refluxed for 15 hrs After cooling the precipitated crystals were collected by filtration recrystallized from hexane-ethanol

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

Procedure: A mixture of methyl thiosalicylate (2.00 g, 11.8 mmol), pyrrole-2-carbonitrile (1.10 g, 11.9 mmol), triethylamine (2.00 ml, 14.3 mmol) and toluene (4.0 ml) was refluxed for 15 hrs as described in Example 1. After cooling, the precipitated crystals were collected by filtration and recrystallized from hexane-ethanol to give the titled compound (1.90 g, 73%). was refluxed for 15 hrs After cooling the precipitated crystals were collected by filtration recrystallized from hexane-ethanol

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

Procedure: 51.57 g of 2-cyano-pyrrol[prepared by the process of Can. J. Chem. Vol. 59, p. 2763 (1981)], 146.9 g of triphenylphosphine, and 43.95 g of propargyl alcohol were mixed together and 420 ml of tetrahydrofuran were added. The mixture was cooled at +5° C., and over half an hour at 0° to 5° C., 97.5 g of ethyl azodicarboxylate were introduced. The temperature was allowed to return to ambient, and stirring was maintained for 18 hours. The solvent was evaporated under reduced pressure, and the crystallized residue was taken up in ethyl ether and filtered. After concentrating the filtrate, an oil was obtained which was chromatographed over silica. Elution with a hexane-ethyl acetate (7-3) mixture yielded 34 g of 1-(2-propynyl)-1H-pyrrole-2-carbonitrile. The mixture was cooled at +5° C. over half an hour at 0° to 5° C. was maintained for 18 hours The solvent was evaporated under reduced pressure filtered After concentrating the filtrate an oil was obtained which was chromatographed over silica Elution with a hexane-ethyl acetate (7-3) mixture

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

Procedure: A solution of 10 g 1H-pyrrole-2-carbonitrile and 1 eq sodium methoxide in 20 ml ethanol and stirred for 10 min. Hydrazine hydrate (3 eq.) is then added and resulting reaction mixture is stirred at room temperature for 18 h. The Reaction mixture is then diluted with water, extracted with ethyl acetate, dried over Na2SO4 and concentrated under vacuum to yield desired compound. resulting reaction mixture extracted with ethyl acetate dried over Na2SO4 concentrated under vacuum

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

Procedure: A mixture of methyl thiosalicylate (2.00 g, 11.8 mmol), pyrrole-2-carbonitrile (1.10 g, 11.9 mmol), triethylamine (2.00 ml, 14.3 mmol) and toluene (4.0 ml) was refluxed for 15 hrs as described in Example 1. After cooling, the precipitated crystals were collected by filtration and recrystallized from hexane-ethanol to give the titled compound (1.90 g, 73%). was refluxed for 15 hrs After cooling the precipitated crystals were collected by filtration recrystallized from hexane-ethanol

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

Procedure: A mixture of methyl thiosalicylate (2.00 g, 11.8 mmol), pyrrole-2-carbonitrile (1.10 g, 11.9 mmol), triethylamine (2.00 ml, 14.3 mmol) and toluene (4.0 ml) was refluxed for 15 hrs as described in Example 1. After cooling, the precipitated crystals were collected by filtration and recrystallized from hexane-ethanol to give the titled compound (1.90 g, 73%). was refluxed for 15 hrs After cooling the precipitated crystals were collected by filtration recrystallized from hexane-ethanol

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

Procedure: Friedel-Crafts alkylation reactions have been utilized by prior workers to synthesize 4-substituted-pyrrole-2-carbaldehyde compounds. For example, Anderson et.al. (Can. J. Chem. 56, 654-657 (1978)) reacted pyrrole-2-carbonitrile with t-butyl chloride in the presence of aluminum or gallium chloride catalysts, to obtain either 4-t-butyl-pyrrole-2-carbonitrile, or 5-t-butyl-pyrrole-2-carbonitrile. Each of the two isomers of the t-butyl-pyrrole-2-carbonitriles were then reduced to the corresponding aldehydes.

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

Procedure: Friedel-Crafts alkylation reactions have been utilized by prior workers to synthesize 4-substituted-pyrrole-2-carbaldehyde compounds. For example, Anderson et.al. (Can. J. Chem. 56, 654-657 (1978)) reacted pyrrole-2-carbonitrile with t-butyl chloride in the presence of aluminum or gallium chloride catalysts, to obtain either 4-t-butyl-pyrrole-2-carbonitrile, or 5-t-butyl-pyrrole-2-carbonitrile. Each of the two isomers of the t-butyl-pyrrole-2-carbonitriles were then reduced to the corresponding aldehydes.

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

Procedure: Friedel-Crafts alkylation reactions have been utilized by prior workers to synthesize 4-substituted-pyrrole-2-carbaldehyde compounds. For example, Anderson et.al. (Can. J. Chem. 56, 654-657 (1978)) reacted pyrrole-2-carbonitrile with t-butyl chloride in the presence of aluminum or gallium chloride catalysts, to obtain either 4-t-butyl-pyrrole-2-carbonitrile, or 5-t-butyl-pyrrole-2-carbonitrile. Each of the two isomers of the t-butyl-pyrrole-2-carbonitriles were then reduced to the corresponding aldehydes.

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 51.57 g of 2-cyano-pyrrol[prepared by the process of Can. J. Chem. Vol. 59, p. 2763 (1981)], 146.9 g of triphenylphosphine, and 43.95 g of propargyl alcohol were mixed together and 420 ml of tetrahydrofuran were added. The mixture was cooled at ±5° C., and over half an hour at 0° to 5° C., 97.5 g of ethyl azodicarboxylate were introduced. The temperature was allowed to return to ambient, and stirring was maintained for 18 hours. The solvent was evaporated under reduced pressure, and the crystallized residue was taken up in ethyl ether and filtered. After concentrating the filtrate, an oil was obtained which was chromatographed over silica. Elution with a hexane-ethyl acetate (7-3) mixture yielded 34 g of 1-(2-propynyl)-1H-pyrrole-2-carbonitrile. over half an hour at 0° to 5° C. was maintained for 18 hours The solvent was evaporated under reduced pressure filtered After concentrating the filtrate an oil was obtained which was chromatographed over silica Elution with a hexane-ethyl acetate (7-3) mixture