benzene-1,2-diamine;dihydrochloride

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

Procedure: To a 1 liter four-neck flask equipped with a mechanical stirrer, a condenser, pH probe and thermometer were added 54 grams (0.5 mole) of 4-cyanothiazole, 90.5 grams (0.5 mole) of o-phenylenediamine dihydrochloride and 250 ml of deionized water. Sodium hydroxide pellets were added in sufficient proportion to increase the pH of the reaction mixture to a value of 4.0. The mixture was heated to reflux and held at reflux (100°-102° C.) for 4 hours. The reaction was determined to be complete when the peaks corresponding to o-phenylenediamine and 4-cyanothiazole were absent from the gas chromatogram. The reaction mass was allowed to cool to room temperature before adding 0.1N NaOH to adjust the pH to a value within a range of 8-10. The product was filtered, washed three times with 300 ml portions of deionized water, and then dried overnight in a vacuum oven. A total of 78.0 grams of thiabendazole were obtained which corresponds to a 77.5% yield. To a 1 liter four-neck flask equipped with a mechanical stirrer, a condenser to increase the pH of the reaction mixture to a value of 4.0 The mixture was heated to reflux at reflux (100°-102° C.) for 4 hours The product was filtered washed three times with 300 ml portions of deionized water dried overnight in a vacuum oven

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

Procedure: Following the general procedure described in A. R. Friedman, D. S. Payne and A. R. Day, J. Heterocyclic Chemistry, 3:257-259(1966), a mixture of 9 g of 1,2-phenylenediamine dihydrochloride and 7 g of 2-methylbutyrolactone in 60 mL of 4N hydrochloric acid was heated to reflux for 4 days, 1 teaspoon of decolorizing carbon added, and after another 15 min reflux, filtered hot. The filtrate was concentrated under reduced pressure to near dryness, the residue made basic (pH=8) with ammonium hydroxide and extracted into 3×100 mL of ethyl acetate. The combined extracts were dried over magnesium sulfate and concentrated under reduced pressure. After drying under vacuum, 12 g of 3-(1H-benzimidazol-2-yl)-butan-1-ol was obtained as a resin. was heated to reflux for 4 days 1 teaspoon of decolorizing carbon added after another 15 min reflux filtered hot The filtrate was concentrated under reduced pressure extracted into 3×100 mL of ethyl acetate The combined extracts were dried over magnesium sulfate concentrated under reduced pressure After drying under vacuum

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

Procedure: Preparation analogous to 16), S43, using 16.1 g (100 mmol) of 2-tert-butyl-5-cyanopyrimidine [126230-72-6] and 71.4 g (300 mmol) of 3,4-diamino-6-tert-butylpyridine dihydrochloride (S50) instead of 25.9 g (100 mmol) of 2-N-pivaloylamido-3-cyano-6-tert-butylpyridine (S42) and 90.5 g (500 mmol) of o-phenylenediamine dihydrochloride [615-28-1]. After cooling, the violet melt is dissolved in a mixture of 150 ml of ethanol and 300 ml of water at elevated temperature, and a solution of 25 g of sodium carbonate in 100 ml of water is then added dropwise with vigorous stirring (note: foaming, evolution of carbon dioxide). When the addition is complete, the mixture is stirred for a further 30 min., the brown solid is then filtered off with suction, washed three times with 100 ml of water each time and dried in vacuo. Yield: 23.8 g (77 mmol), 77%. Purity: >95% according to 1H-NMR. Preparation analogous to 16), S43 After cooling When the addition the brown solid is then filtered off with suction washed three times with 100 ml of water each time dried in vacuo

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

Procedure: Preparation analogous to 16), S43, using 16.1 g (100 mmol) of 2-tert-butyl-5-cyanopyrimidine [126230-72-6] and 71.4 g (300 mmol) of 3,4-diamino-6-tert-butylpyridine dihydrochloride (S50) instead of 25.9 g (100 mmol) of 2-N-pivaloylamido-3-cyano-6-tert-butylpyridine (S42) and 90.5 g (500 mmol) of o-phenylenediamine dihydrochloride [615-28-1]. After cooling, the violet melt is dissolved in a mixture of 150 ml of ethanol and 300 ml of water at elevated temperature, and a solution of 25 g of sodium carbonate in 100 ml of water is then added dropwise with vigorous stirring (note: foaming, evolution of carbon dioxide). When the addition is complete, the mixture is stirred for a further 30 min., the brown solid is then filtered off with suction, washed three times with 100 ml of water each time and dried in vacuo. Yield: 23.8 g (77 mmol), 77%. Purity: >95% according to 1H-NMR. Preparation analogous to 16), S43 After cooling When the addition the brown solid is then filtered off with suction washed three times with 100 ml of water each time dried in vacuo

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

Procedure: In analogy to the preparation of 8, 1.89 g of a 30% NaOCH3 solution were added to tert-butyl (4-cyano-1,3-thiazol-2-yl)methylcarbamate (2.5 g; 10.45 mmol) in 25 ml of CH3OH, and the mixture was stirred at room temperature for 2 h. Addition of 1.9 g of 1,2-phenylenediamine bishydrochloride was followed by stirring overnight, and then the reaction mixture was added to 100 ml of H2O, and the solid resulting after filtration was dried in vacuo. by stirring overnight the solid resulting after filtration was dried in vacuo

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

Procedure: In analogy to the preparation of 8, 1.89 g of a 30% NaOCH3 solution were added to tert-butyl (4-cyano-1,3-thiazol-2-yl)methylcarbamate (2.5 g; 10.45 mmol) in 25 ml of CH3OH, and the mixture was stirred at room temperature for 2 h. Addition of 1.9 g of 1,2-phenylenediamine bishydrochloride was followed by stirring overnight, and then the reaction mixture was added to 100 ml of H2O, and the solid resulting after filtration was dried in vacuo. by stirring overnight the solid resulting after filtration was dried in vacuo

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

Procedure: 3.32 g of a 30% NaOCH3 solution were added to tert-butyl cyanomethylcarbamate (3 g; 19.21 mmol) in 20 ml of CH3OH, and the mixture was stirred at room temperature for 1 h. After addition of 3.4 g of 1,2-phenylenediamine bishydrochloride, the reaction mixture was stirred further overnight and then added to 100 ml of H2O, and the resulting solid was filtered off and dried in vacuo. the reaction mixture was stirred further overnight the resulting solid was filtered off dried in vacuo

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

Procedure: 3.32 g of a 30% NaOCH3 solution were added to tert-butyl cyanomethylcarbamate (3 g; 19.21 mmol) in 20 ml of CH3OH, and the mixture was stirred at room temperature for 1 h. After addition of 3.4 g of 1,2-phenylenediamine bishydrochloride, the reaction mixture was stirred further overnight and then added to 100 ml of H2O, and the resulting solid was filtered off and dried in vacuo. the reaction mixture was stirred further overnight the resulting solid was filtered off dried in vacuo

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

Procedure: 3.32 g of a 30% NaOCH3 solution were added to tert-butyl cyanomethylcarbamate (3 g; 19.21 mmol) in 20 ml of CH3OH, and the mixture was stirred at room temperature for 1 h. After addition of 3.4 g of 1,2-phenylenediamine bishydrochloride, the reaction mixture was stirred further overnight and then added to 100 ml of H2O, and the resulting solid was filtered off and dried in vacuo. the reaction mixture was stirred further overnight the resulting solid was filtered off dried in vacuo

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-cyclopropanecarboxylic acid (4 g, 52 mmol) was treated with phenylenediamine bis-hydrochloride (1 eq) and polyphosphosphoric acid (52 mL) and heated to 160° C. for 6 h. The reaction was cooled to 0° C. and diluted with water, then basified with NaOH (50% aqueous) until pH>10. The solution was extracted with ethyl acetate, dried (MgSO4), filtered and concentrated, purified by flash chromatography (100% ethyl acetate) giving 2-cyclopropylbenzimidazole (1.1 g, 13%). MS found: (M+H)+=159. The reaction was cooled to 0° C. The solution was extracted with ethyl acetate dried (MgSO4) filtered concentrated purified by flash chromatography (100% ethyl acetate)

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Cyclopropanecarboxylic acid (4 g, 52 mmol) was treated with phenylenediamine bis-hydrochloride (1 eq) and polyphosphosphoric acid (52 mL) and heated to 160° C. for 6 h. The reaction was cooled to 0° C. and diluted with water, then basified with NaOH (50% aqueous) until pH>10. The solution was extracted with ethyl acetate, dried (MgSO4), filtered and concentrated, purified by flash chromatography (100% ethyl acetate) giving 2-cyclopropylbenzimidazole (1.1 g, 13%). MS found: (M+H)+=159. The reaction was cooled to 0° C. The solution was extracted with ethyl acetate dried (MgSO4) filtered concentrated purified by flash chromatography (100% ethyl acetate)

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

Procedure: To a 1 liter four-neck flask equipped with a mechanical stirrer, a condenser, pH probe and thermometer were added 54 grams (0.5 mole) of 4-cyanothiazole, 90.5 grams (0.5 mole) of o-phenylenediamine dihydrochloride and 250 ml of deionized water. Sodium hydroxide pellets were added in sufficient proportion to increase the pH of the reaction mixture to a value of 4.0. The mixture was heated to reflux and held at reflux (100°-102° C.) for 4 hours. The reaction was determined to be complete when the peaks corresponding to o-phenylenediamine and 4-cyanothiazole were absent from the gas chromatogram. The reaction mass was allowed to cool to room temperature before adding 0.1N NaOH to adjust the pH to a value within a range of 8-10. The product was filtered, washed three times with 300 ml portions of deionized water, and then dried overnight in a vacuum oven. A total of 78.0 grams of thiabendazole were obtained which corresponds to a 77.5% yield. To a 1 liter four-neck flask equipped with a mechanical stirrer, a condenser to increase the pH of the reaction mixture to a value of 4.0 The mixture was heated to reflux at reflux (100°-102° C.) for 4 hours The product was filtered washed three times with 300 ml portions of deionized water dried overnight in a vacuum oven