3-chloropyrazine-2-carboxaMide

The starting compound 3-chloropyrazine-2-carboxamide was synthesized using two published procedures. The first method was classified as less effective and was based on the homolytic amidation of 2-chloropyrazine. Thus, 2-chloropyrazine (0.17 mol) was dissolved in formamide (3.7 mol), heated to 90 °C and ammonium peroxodisulphate (0.18 mol) was added portionwise over one hour period. This mixture reacted for another one hour at 90 °C and then it was left to stand for 24 h at laboratory temperature. Dilution with 100 mL of water was followed by filtration and this filtrate was extracted continuously with chloroform for 16 h [34, 42]. The mixture of three positional isomers was separated by flash chromatography using silica gel as stationary phase. The second process used 3-chloropyrazine-2-carbonitrile, which was submitted to partial hydrolysis of the nitrile group. The powdered carbonitrile (0.104 mol) was added little by little into the reaction mixture of concentrated hydrogen peroxide (0.95 mol) and water (195 mL) heated to 50 °C. The pH was adjusted and regulated around a value of 9 using an 8percent solution of sodium hydroxide and the temperature of the reaction was regulated between 55 and 60 °C. The reaction was stopped after 2.5 h and was cooled to 5 °C. Newly-emerged crystals were removed by suction and recrystallized from ethanol [42].The starting compound 3-chloropyrazine-2-carboxamide was prepared via partial hydrolysis of the nitrile group of 3-chloropyrazine-2-carbonitrile (Fluorochem, Co., Hadfield, Derbyshire, UK). A mixture of concentrated (30percent) hydrogen peroxide (29 mL) and water (195 mL) was prepared and alkalinized with an 8percent (w/v) solution of sodium hydroxide to obtain a solution with pH 9. The carbonitrile (104 mmol) was then added portionwise into the heated (50 °C) mixture over a period of 30 min. The whole mass was stirred for an additional 2.5 h at 55 °C while the pH was periodically monitored and alternatively adjusted to the value of 9 by adding a few drops of 8percent NaOH solution. The reaction mixture was cooled in a fridge to initiate crystallization. The crude product was recrystallized from ethanol [27]. The yield of this reaction was approximately 80percent.The starting compound 3-chloropyrazine-2-carboxamide was synthesized using two published procedures. The first method was classified as less effective and was based on the homolytic amidation of 2-chloropyrazine. Thus, 2-chloropyrazine (0.17 mol) was dissolved in formamide (3.7 mol), heated to 90 °C and ammonium peroxodisulphate (0.18 mol) was added portionwise over one hour period. This mixture reacted for another one hour at 90 °C and then it was left to stand for 24 h at laboratory temperature. Dilution with 100 mL of water was followed by filtration and this filtrate was extracted continuously with chloroform for 16 h [34, 42]. The mixture of three positional isomers was separated by flash chromatography using silica gel as stationary phase. The second process used 3-chloropyrazine-2-carbonitrile, which was submitted to partial hydrolysis of the nitrile group. The powdered carbonitrile (0.104 mol) was added little by little into the reaction mixture of concentrated hydrogen peroxide (0.95 mol) and water (195 mL) heated to 50 °C. The pH was adjusted and regulated around a value of 9 using an 8percent solution of sodium hydroxide and the temperature of the reaction was regulated between 55 and 60 °C. The reaction was stopped after 2.5 h and was cooled to 5 °C. Newly-emerged crystals were removed by suction and recrystallized from ethanol [42].The starting compound 3-chloropyrazine-2-carboxamide was synthesized using two published procedures. The first method was classified as less effective and was based on the homolytic amidation of 2-chloropyrazine. Thus, 2-chloropyrazine (0.17 mol) was dissolved in formamide (3.7 mol), heated to 90 °C and ammonium peroxodisulphate (0.18 mol) was added portionwise over one hour period. This mixture reacted for another one hour at 90 °C and then it was left to stand for 24 h at laboratory temperature. Dilution with 100 mL of water was followed by filtration and this filtrate was extracted continuously with chloroform for 16 h [34, 42]. The mixture of three positional isomers was separated by flash chromatography using silica gel as stationary phase. The second process used 3-chloropyrazine-2-carbonitrile, which was submitted to partial hydrolysis of the nitrile group. The powdered carbonitrile (0.104 mol) was added little by little into the reaction mixture of concentrated hydrogen peroxide (0.95 mol) and water (195 mL) heated to 50 °C. The pH was adjusted and regulated around a value of 9 using an 8percent solution of sodium hydroxide and the temperature of the reaction was regulated between 55 and 60 °C. The reaction was stopped after 2.5 h and was cooled to 5 °C. Newly-emerged crystals were removed by suction and recrystallized from ethanol [42].The starting compound 3-chloropyrazine-2-carboxamide was prepared via partial hydrolysis of the nitrile group of 3-chloropyrazine-2-carbonitrile (Fluorochem, Co., Hadfield, Derbyshire, UK). A mixture of concentrated (30percent) hydrogen peroxide (29 mL) and water (195 mL) was prepared and alkalinized with an 8percent (w/v) solution of sodium hydroxide to obtain a solution with pH 9. The carbonitrile (104 mmol) was then added portionwise into the heated (50 °C) mixture over a period of 30 min. The whole mass was stirred for an additional 2.5 h at 55 °C while the pH was periodically monitored and alternatively adjusted to the value of 9 by adding a few drops of 8percent NaOH solution. The reaction mixture was cooled in a fridge to initiate crystallization. The crude product was recrystallized from ethanol [27]. The yield of this reaction was approximately 80percent.The starting compound 3-chloropyrazine-2-carboxamide was synthesized using two published procedures. The first method was classified as less effective and was based on the homolytic amidation of 2-chloropyrazine. Thus, 2-chloropyrazine (0.17 mol) was dissolved in formamide (3.7 mol), heated to 90 °C and ammonium peroxodisulphate (0.18 mol) was added portionwise over one hour period. This mixture reacted for another one hour at 90 °C and then it was left to stand for 24 h at laboratory temperature. Dilution with 100 mL of water was followed by filtration and this filtrate was extracted continuously with chloroform for 16 h [34, 42]. The mixture of three positional isomers was separated by flash chromatography using silica gel as stationary phase. The second process used 3-chloropyrazine-2-carbonitrile, which was submitted to partial hydrolysis of the nitrile group. The powdered carbonitrile (0.104 mol) was added little by little into the reaction mixture of concentrated hydrogen peroxide (0.95 mol) and water (195 mL) heated to 50 °C. The pH was adjusted and regulated around a value of 9 using an 8percent solution of sodium hydroxide and the temperature of the reaction was regulated between 55 and 60 °C. The reaction was stopped after 2.5 h and was cooled to 5 °C. Newly-emerged crystals were removed by suction and recrystallized from ethanol [42].

Molecular Weight:157.56
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:157.0042895
Monoisotopic Mass:157.0042895
Topological Polar Surface Area:68.9
Heavy Atom Count:10
Complexity:141
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes