3-oxo-3-(1H-pyrrol-2-yl)propanenitrile

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: A solution of 2.1 g of 2-pyrroloylacetonitrile in 15 ml of glyme and 1.8 g of Et3N is treated with a solution of 3 g of 2,4-dichlorophenyl isocyanate in 15 ml of glyme similarly to the preceding examples. Mildly exothermic reaction results in formation of a thick suspension of crystals. After standing overnight, dilution with dry ether and filtration gives the triethylamine salt of β-oxo-α-(2,4-dichlorophenylcarbamoyl)-β-(2-pyrrolyl)-propionitrile, m.p. 180°-2° dec., in form of the enol structure as represented by formula Ia, wherein Py is 2-pyrrolyl, R is hydrogen and Ph is 2,4-dichlorophenyl. Mildly exothermic reaction results in formation of a thick suspension of crystals dilution with dry ether and filtration

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

Procedure: Reaction of 2.0 g of 2-pyrroloylacetonitrile with 3.0 g of 3-(trifluoromethyl)-phenyl isocyanate in the presence of 1.8 g of Et3N in 25 ml of glyme similarly to the previous examples and recrystallization of the crude product from methanol gives β-oxo-α-(3-trifluoromethylphenylcarbamoyl)-β-(2-pyrrolyl)-propionitrile, m.p. 210°-212°.

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

Procedure: Reaction of 2.4 g of 2-pyrroloylacetonitrile with 3.1 g of 2,4-difluorophenyl isocyanate in the presence of 2.0 g Et3N in 25 ml of glyme and isolation similarly to the preceding examples, followed by trituration with and recrystallization from ethanol gives β-oxo-α-(2,4-difluorophenylcarbamoyl)-β-(2-pyrrolyl)-propionitrile, m.p. 169°-171°. recrystallization from ethanol

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

Procedure: To the solution of 6.7 g of 2-pyrroloylacetonitrile in 25 ml of glyme and 5.5 g of Et3N is added a solution of 8.6 g of 4-chlorophenyl isocyanate in 25 ml of glyme. After the exothermic reaction, the mixture is let stand overnight. Part of the solvent is evaporated and the cooled residue is poured into a solution of 10 ml of 6N HCl in 250 ml of water. After the addition of some methanol, the crude material is collected. It is dissolved in dilute NaOH solution, the solution is treated with charcoal, filtered, and acidified with 6N HCl. The reprecipitated product is collected, washed with water, and triturated with methanol to give solid, m.p. 219°-221°. Recrystallization from methanol gives β-oxo-α-(4-chlorophenyl carbamoyl)-β-(2-pyrrolyl)propionitrile, m.p. 223°-5°. After the exothermic reaction Part of the solvent is evaporated the cooled residue is poured into a solution of 10 ml of 6N HCl in 250 ml of water After the addition of some methanol the crude material is collected It is dissolved in dilute NaOH solution the solution is treated with charcoal filtered The reprecipitated product is collected washed with water triturated with methanol to give solid, m.p. 219°-221° Recrystallization from methanol

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

Procedure: Into an ice-chilled solution of 30 g of pyrrole and 30 g of malononitrile in 800 ml of dry ether is passed by HCl for 20 minutes. After standing several hours the suspension is filtered to give 65 g of orange-brown, water-soluble solid. The solution of 50 g of this intermediate (the enamine nitrile hydrochloride) in 600 ml of water is covered with 400 ml of ethyl acetate and stirred for 21/2 hours at room temperature. The organic layer is separated, dried (MgSO4) and evaporated to give crystals, m.p. 77°-9°; additional product is obtained by warming the aqueous layer on steam cone for 1/2 hour and extracting with ethyl acetate. Recrystallization from water gives 2-pyrroloylacetonitrile, m.p. 79°-81°. After standing several hours the suspension is filtered to give 65 g of orange-brown, water-soluble solid The organic layer is separated dried (MgSO4) evaporated to give crystals, m.p. 77°-9° additional product is obtained by warming the aqueous layer on steam cone for 1/2 hour extracting with ethyl acetate Recrystallization from water

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

Procedure: A solution of 3.1 g of 2-pyrroloylacetonitrile in 25 ml of glyme (ethylene glycol dimethyl ether) and 2.7 g of anhydrous triethylamine is treated with 3.0 g of phenyl isocyanate. After the moderately exothermic reaction, the mixture is let stand overnight. Most of the solvent is evaporated and the residue is treated with water and 12 ml of 10% NaOH solution. The aqueous, alkaline solution is washed with ethyl acetate and acidified with 6N HCl. The product is collected, washed with water, dried and recrystallized from ethanol, to give β-oxo-α-(phenylcarbamoyl)-β-(2-pyrrolyl)-propionitrile, m.p. 207°-209°, the compound of formula II, wherein R1 to R4 are hydrogen. After the moderately exothermic reaction Most of the solvent is evaporated the residue is treated with water and 12 ml of 10% NaOH solution The aqueous, alkaline solution is washed with ethyl acetate The product is collected washed with water dried recrystallized from ethanol

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

Procedure: A solution of 2.1 g of 2-pyrroloylacetonitrile in 15 ml of glyme and 1.8 g of Et3N is treated with a solution of 3 g of 2,4-dichlorophenyl isocyanate in 15 ml of glyme similarly to the preceding examples. Mildly exothermic reaction results in formation of a thick suspension of crystals. After standing overnight, dilution with dry ether and filtration gives the triethylamine salt of β-oxo-α-(2,4-dichlorophenylcarbamoyl)-β-(2-pyrrolyl)-propionitrile, m.p. 180°-2° dec., in form of the enol structure as represented by formula Ia, wherein Py is 2-pyrrolyl, R is hydrogen and Ph is 2,4-dichlorophenyl. Mildly exothermic reaction results in formation of a thick suspension of crystals dilution with dry ether and filtration

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

Procedure: Reaction of 2.0 g of 2-pyrroloylacetonitrile with 3.0 g of 3-(trifluoromethyl)-phenyl isocyanate in the presence of 1.8 g of Et3N in 25 ml of glyme similarly to the previous examples and recrystallization of the crude product from methanol gives β-oxo-α-(3-trifluoromethylphenylcarbamoyl)-β-(2-pyrrolyl)-propionitrile, m.p. 210°-212°.