benzene-1,2-diamine;hydrochloride

反応条件: temp:201.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The mixture was heated and when the pot temperature reached 164° C., distillation commenced. The temperature gradually increased to 201° C. and a total of 44 ml of water plus ethylene glycol distillate were removed. The mixture was allowed to cool to 100° C. before 27.5 g (0.25 moles) of 4-cyanothiazole were added to the solution containing o-phenylenediamine monohydrochloride. The reaction mixture was heated to 125° C. and held within a temperature range of 125°-130° C. for a period of 5 hours. Thiabendazole formed as a precipitte during the 5 hours of heating. The reaction was monitored by gas chromatography and determined to be complete when the peaks corresponding to o-phenylenediamine and 4-cyanothiazole were negligible. Next, the reaction mass was cooled to 50° C. and filtered to collect the precipitate using a Buchner funnel and #4 Whatman filter paper. The wet cake was washed with 1.5 L of deionized water. The washed precipitate was dried overnight in a vacuum oven under 15-20" Hg and at a temperature of 90° C. The weight of dry thiabendazole crystals was 38.0 g, which corresponds to a yield of 75.5%. The purity was determined to be 99.67% (based on area %) using HPLC analysis. The mixture was heated reached 164° C. distillation a total of 44 ml of water plus ethylene glycol distillate were removed were added to the solution The reaction mixture was heated to 125° C.

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

実験手順: In a preferred embodiment, to a suitable reaction vessel is charged water containing trace amounts of ascorbic acid, an antioxidant, and ethylenediaminetetraacetic acid (EDTA), a metal deactivator. Because o-phenylene-diamine is sensitive to dissolved oxygen in solvents, ascorbic acid which functions as an oxidation inhibitor is added prior to o-phenylenediamine. EDTA, which complexes with metals is also added and prevents metal oxidation of o-phenylenediamine. The system is purged with nitrogen to remove air and a nitrogen blanket is maintained for the duration of the reaction. The aqueous solution is heated using an oil bath, and when the pot temperature reaches 95° C., o-phenylenediamine is added. Since water deoxygenates on heating, o-phenylene-iamine is added to a heated reaction medium with less dissolved oxygen present to react with o-phenylenediamine. Hydrochloric acid is added in a controlled manner to adjust the pH of the reaction mixture to a desired level and the amount used is recorded. An exothermic acid-base reaction occurs and o-phenylenediamine monohydrochloride salt is formed. A stoichiometric amount of 4-cyanothiazole is charged to the reaction vessel. Following addition of 4-cyanothiazole, the reaction mixture is heated to reflux (103°-104° C.). During the reaction, the pH is maintained within +/-0.2 of the desired level by periodic addition of concentrated hydrochloric acid. Since thiabendazole is only slightly soluble in water, the product precipitates as it is formed in the reaction mixture. The reaction is monitored by gas chromatography and determined to be complete when the peaks corresponding to o-phenylenediamine and 4-cyanothiazole are negligible. Upon completion of the reaction, the reaction mass is cooled to 50° C. A sufficient amount of 50° C. deionized water is added to dilute the reaction mass and the solid product is separated from the mother liquor by vacuum filtration. The filtered cake is washed with portions of fresh deionized water until the filtrate gives a negative test for chloride ion using AgNO3 solution which indicates the ammonium chloride coproduct is removed. The solid thiabendazole product is dried in a vacuum oven under 15-20" Hg and at a temperature of 80°-90° C. is added The system is purged with nitrogen to remove air a nitrogen blanket is maintained for the duration of the reaction The aqueous solution is heated reaches 95° C. o-phenylenediamine is added on heating o-phenylene-iamine is added to a heated reaction medium with less dissolved oxygen present to react with o-phenylenediamine An exothermic acid-base reaction

反応条件: temp:201.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The mixture was heated and when the pot temperature reached 164° C., distillation commenced. The temperature gradually increased to 201° C. and a total of 44 ml of water plus ethylene glycol distillate were removed. The mixture was allowed to cool to 100° C. before 27.5 g (0.25 moles) of 4-cyanothiazole were added to the solution containing o-phenylenediamine monohydrochloride. The reaction mixture was heated to 125° C. and held within a temperature range of 125°-130° C. for a period of 5 hours. Thiabendazole formed as a precipitte during the 5 hours of heating. The reaction was monitored by gas chromatography and determined to be complete when the peaks corresponding to o-phenylenediamine and 4-cyanothiazole were negligible. Next, the reaction mass was cooled to 50° C. and filtered to collect the precipitate using a Buchner funnel and #4 Whatman filter paper. The wet cake was washed with 1.5 L of deionized water. The washed precipitate was dried overnight in a vacuum oven under 15-20" Hg and at a temperature of 90° C. The weight of dry thiabendazole crystals was 38.0 g, which corresponds to a yield of 75.5%. The purity was determined to be 99.67% (based on area %) using HPLC analysis. The mixture was heated reached 164° C. distillation a total of 44 ml of water plus ethylene glycol distillate were removed were added to the solution The reaction mixture was heated to 125° C.

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

実験手順: In a preferred embodiment, to a suitable reaction vessel is charged water containing trace amounts of ascorbic acid, an antioxidant, and ethylenediaminetetraacetic acid (EDTA), a metal deactivator. Because o-phenylene-diamine is sensitive to dissolved oxygen in solvents, ascorbic acid which functions as an oxidation inhibitor is added prior to o-phenylenediamine. EDTA, which complexes with metals is also added and prevents metal oxidation of o-phenylenediamine. The system is purged with nitrogen to remove air and a nitrogen blanket is maintained for the duration of the reaction. The aqueous solution is heated using an oil bath, and when the pot temperature reaches 95° C., o-phenylenediamine is added. Since water deoxygenates on heating, o-phenylene-iamine is added to a heated reaction medium with less dissolved oxygen present to react with o-phenylenediamine. Hydrochloric acid is added in a controlled manner to adjust the pH of the reaction mixture to a desired level and the amount used is recorded. An exothermic acid-base reaction occurs and o-phenylenediamine monohydrochloride salt is formed. A stoichiometric amount of 4-cyanothiazole is charged to the reaction vessel. Following addition of 4-cyanothiazole, the reaction mixture is heated to reflux (103°-104° C.). During the reaction, the pH is maintained within +/-0.2 of the desired level by periodic addition of concentrated hydrochloric acid. Since thiabendazole is only slightly soluble in water, the product precipitates as it is formed in the reaction mixture. The reaction is monitored by gas chromatography and determined to be complete when the peaks corresponding to o-phenylenediamine and 4-cyanothiazole are negligible. Upon completion of the reaction, the reaction mass is cooled to 50° C. A sufficient amount of 50° C. deionized water is added to dilute the reaction mass and the solid product is separated from the mother liquor by vacuum filtration. The filtered cake is washed with portions of fresh deionized water until the filtrate gives a negative test for chloride ion using AgNO3 solution which indicates the ammonium chloride coproduct is removed. The solid thiabendazole product is dried in a vacuum oven under 15-20" Hg and at a temperature of 80°-90° C. is added The system is purged with nitrogen to remove air a nitrogen blanket is maintained for the duration of the reaction The aqueous solution is heated reaches 95° C. o-phenylenediamine is added on heating o-phenylene-iamine is added to a heated reaction medium with less dissolved oxygen present to react with o-phenylenediamine An exothermic acid-base reaction