2,4-二硫代缩二脲

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirring solution of dithiobiuret (5.0 g, 37 mmol) in THF (75 mL) was added iodomethane (13.1 g, 92.5 mmol, 5.76 μl). After stirring at room temperature for 22 h, the solution was diluted with 150 mL of toluene and allowed to stand at 0° C. for 3 h. The crystals were collected by filtration and washed with cold 2:1 toluene/THF, then dried in vacuo to give the title compound as a white solid (8.7 g, 85%). MS(ESI): 149.9 (M+H)+. to stand at 0° C. for 3 h The crystals were collected by filtration washed with cold 2:1 toluene/THF dried in vacuo

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The S-octyldithiobiuret was prepared as follows: To 135 g of dithiobiuret in 300 ml ethyleneglycol monomethyl ether were added 210 g of n-octyl bromide dropwise at 70°C. After 12 hours the solvent was distilled off at 12 mm. The residue was dissolved in toluene and hexane was added after which the mixture was cooled at 0°C. The solvent was decanted from the semicrystalline precipitate which was dissolved again in glacial acetic acid. The solution was poured on icewater and stirred for 2 hours. The solid was filtered, stirred with hexane in a beaker until it had completely crystallized, filtered and dried. The product had a melting point of 75°-77°C. After 12 hours the solvent was distilled off at 12 mm The residue was dissolved in toluene hexane was added after which the mixture The solvent was decanted from the semicrystalline precipitate which was dissolved again in glacial acetic acid The solution was poured on icewater The solid was filtered stirred with hexane in a beaker until it had completely crystallized filtered dried

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The S-octyldithiobiuret was prepared as follows: To 135 g of dithiobiuret in 300 ml ethyleneglycol monomethyl ether were added 210 g of n-octyl bromide dropwise at 70°C. After 12 hours the solvent was distilled off at 12 mm. The residue was dissolved in toluene and hexane was added after which the mixture was cooled at 0°C. The solvent was decanted from the semicrystalline precipitate which was dissolved again in glacial acetic acid. The solution was poured on icewater and stirred for 2 hours. The solid was filtered, stirred with hexane in a beaker until it had completely crystallized, filtered and dried. The product had a melting point of 75°-77°C. After 12 hours the solvent was distilled off at 12 mm The residue was dissolved in toluene hexane was added after which the mixture The solvent was decanted from the semicrystalline precipitate which was dissolved again in glacial acetic acid The solution was poured on icewater The solid was filtered stirred with hexane in a beaker until it had completely crystallized filtered dried

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirring solution of dithiobiuret (5.0 g, 37 mmol) in THF (75 mL) was added iodomethane (13.1 g, 92.5 mmol, 5.76 ml). After stirring at room temperature for 22 h, the solution was diluted with 150 mL of toluene and allowed to stand at 0° C. for 3 h. The crystals were collected by filtration and washed with cold 2:1 toluene/THF, then dried in vacuo to give the title compound as a white solid (8.7 g, 85%). MS(ESI): 149.9 (M+H)+. to stand at 0° C. for 3 h The crystals were collected by filtration washed with cold 2:1 toluene/THF dried in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirring solution of dithiobiuret (5.0 g, 37 mmol) in THF (75 mL) was added iodomethane (13.1 g, 92.5 mmol, 5.76 ml). After stirring at room temperature for 22 h, the solution was diluted with 150 mL of toluene and allowed to stand at 0° C. for 3 h. The crystals were collected by filtration and washed with cold 2:1 toluene/THF, then dried in vacuo to give the title compound as a white solid (8.7 g, 85%). MS(ESI): 149.9 (M+H)+. to stand at 0° C. for 3 h The crystals were collected by filtration washed with cold 2:1 toluene/THF dried in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirring solution of dithiobiuret (5.0 g, 37 mmol) in THF (75 mL) was added iodomethane (13.1 g, 92.5 mmol, 5.76 ml). After stirring at room temperature for 22 h, the solution was diluted with 150 mL of toluene and allowed to stand at 0° C. for 3 h. The crystals were collected by filtration and washed with cold 2:1 toluene/THF, then dried in vacuo to give the title compound as a white solid (8.7 g, 85%). MS(ESI): 149.9 (M+H)+. to stand at 0° C. for 3 h The crystals were collected by filtration washed with cold 2:1 toluene/THF dried in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirring solution of dithiobiuret (5.0 g, 37 mmol) in THF (75 mL) was added iodomethane (13.1 g, 92.5 mmol, 5.76 ml). After stirring at room temperature for 22 h, the solution was diluted with 150 mL of toluene and allowed to stand at 0° C. for 3 h. The crystals were collected by filtration and washed with cold 2:1 toluene/THF, then dried in vacuo to give the title compound as a white solid (8.7 g, 85%). MS(ESI): 149.9 (M+H)+. to stand at 0° C. for 3 h The crystals were collected by filtration washed with cold 2:1 toluene/THF dried in vacuo

反应条件: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2.00 g (14.8 mmol) dithiobiuret were placed in 25 ml methanol and 2.10 g (14.8 mmol) methyliodide were added at room temperature. The mixture was heated for 3 hours at reflux, then the solution was concentrated, was diluted with 25 ml of ethanol and 2.47 g (14.8 mmol) 2,6-dimethoxybenzylamine were added. The mixture was subsequently stirred again for 2 hours at reflux and subsequently for 30 minutes at 5° C. Filtration of the precipitate formed yielded 970 mg N-[[(2,6-dimethoxybenzyl)amino](imino)methyl]thiourea. The mixture was heated for 3 hours at reflux the solution was concentrated were added Filtration of the precipitate formed

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirring solution of dithiobiuret (5.0 g, 37 mmol) in THF (75 mL) was added iodomethane (13.1 g, 92.5 mmol, 5.76 μl). After stirring at room temperature for 22 h, the solution was diluted with 150 mL of toluene and allowed to stand at 0° C. for 3 h. The crystals were collected by filtration and washed with cold 2:1 toluene/THF, then dried in vacuo to give the title compound as a white solid (8.7 g, 85%). MS(ESI): 149.9 (M+H)+. to stand at 0° C. for 3 h The crystals were collected by filtration washed with cold 2:1 toluene/THF dried in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirring solution of dithiobiuret (5.0 g, 37 mmol) in THF (75 mL) was added iodomethane (13.1 g, 92.5 mmol, 5.76 μl). After stirring at room temperature for 22 h, the solution was diluted with 150 mL of toluene and allowed to stand at 0° C. for 3 h. The crystals were collected by filtration and washed with cold 2:1 toluene/THF, then dried in vacuo to give the title compound as a white solid (8.7 g, 85%). MS(ESI): 149.9 (M+H)+. to stand at 0° C. for 3 h The crystals were collected by filtration washed with cold 2:1 toluene/THF dried in vacuo

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The S-octyldithiobiuret was prepared as follows: To 135 g of dithiobiuret in 300 ml ethyleneglycol monomethyl ether were added 210 g of n-octyl bromide dropwise at 70°C. After 12 hours the solvent was distilled off at 12 mm. The residue was dissolved in toluene and hexane was added after which the mixture was cooled at 0°C. The solvent was decanted from the semicrystalline precipitate which was dissolved again in glacial acetic acid. The solution was poured on icewater and stirred for 2 hours. The solid was filtered, stirred with hexane in a beaker until it had completely crystallized, filtered and dried. The product had a melting point of 75°-77°C. After 12 hours the solvent was distilled off at 12 mm The residue was dissolved in toluene hexane was added after which the mixture The solvent was decanted from the semicrystalline precipitate which was dissolved again in glacial acetic acid The solution was poured on icewater The solid was filtered stirred with hexane in a beaker until it had completely crystallized filtered dried

实验步骤: 投料: 准备100L反应釜1，加入水（40kg,8V）,加入二氰胺钠（500 kg, 1.eq），加入硫氢化钠（70%，13.5kg, 3.0eq），氮气置换三次（反应全程保持氮气氛围）升温至75℃并在75℃保温搅拌2h,TLC监测反应（DCM:MEOH=4:1,茚三酮显色），LCMS-8min监测有无新杂质，待反应完全，降温至25℃，反应液转移至转料桶。准备100L反应釜2，加入水（20kg,4V）,降温至10℃，加入盐酸（24kg,4.2eq），准备100L反应釜1，加入水（60kg,15V）,降温至10℃，加入氢氧化钠（15kg,6.7eq）作尾气硫化氢的吸收装置。转料桶中反应液缓慢滴加入到反应釜2，滴加时间6h，滴毕搅拌1h,，过滤（滤固1为产品），滤固1加入到反应釜1，加入水(75kg，15V),升温至100℃并在100℃保温回流搅拌2h，趁热过滤，过滤（滤液1为产品），滤液转移至反应釜1，25℃搅拌2h，过滤得黄色固体（滤固2为产品），准备50L反应釜，加入滤固2，加入THF(20L,4V),加入活性炭（1.2kg），硅胶1.0kg，搅拌3h,过滤（滤液为产品），滤液42℃真空浓缩，得4.5kg类白色固体3，固体4加入30L反应釜,加入95%乙醇（6kg，1.5V）,升温至80℃，回流保温2h，降温至5℃，保温2h，过滤，45℃真空烘干，得3.0kg白色固体 \n辅助生产