N-methylbenzenecarbothiohydrazide

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: Bromobenzene (1.6 g, 10 mmol) was added into 25 ml anhydrous THF solution containing magnesium powder (0.3 g, 12.5 mmol), and refluxed for 2 hr. After it was cooled, the clear reaction solution was added into carbon disulfide (1 ml, 16.8 mmol) at 0° C., and stirred for 30 min at rt. The resulting mixture was then added into methylhydrazine (1.6 ml, 30 mmol) at 0° C., and stirred for another 2 hours. To this solution was added water (15 ml) and extracted with EtOAc (30 ml×3). The organic solution was concentrated to minimum volume, and subjected to silica gel column chromatography (eluant: 1:3-1:1 ethyl acetate: hexanes) to give thiobenzoic acid N-methyl hydrazide (0.72 g, total yield: 48%). 1H NMR (CDCl3) δ 3.3 (s, 3H), 6.0 (s, 2H), 7.3-7.4 (m, 5H); ESMS calcd (C8H10N2S): 166.1; found: 167.1 (M+H)+. refluxed for 2 hr After it was cooled stirred for another 2 hours extracted with EtOAc (30 ml×3) The organic solution was concentrated to minimum volume

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: Bromobenzene (1.6 g, 10 mmol) was added into 25 ml anhydrous THF solution containing magnesium powder (0.3 g, 12.5 mmol), and refluxed for 2 hr. After it was cooled, the clear reaction solution was added into carbon disulfide (1 ml, 16.8 mmol) at 0° C., and stirred for 30 min at rt. The resulting mixture was then added into methylhydrazine (1.6 ml, 30 mmol) at 0° C., and stirred for another 2 hours. To this solution was added water (15 ml) and extracted with EtOAc (30 ml×3). The organic solution was concentrated to minimum volume, and subjected to silica gel column chromatography (eluant: 1:3−1:1 ethyl acetate: hexanes) to give thiobenzoic acid N1-methyl hydrazide (0.72 g, total yield: 48%). 1H NMR (CDCl3) δ 3.3 (s, 3H), 6.0 (s, 2H), 7.3-7.4 (m, 5H); ESMS calcd (C8H10N2S): 166.1; found: 167.1 (M+H)+. refluxed for 2 hr After it was cooled stirred for another 2 hours extracted with EtOAc (30 ml×3) The organic solution was concentrated to minimum volume

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

実験手順: Bromobenzene (1.6 g, 10 mmol) was added into 25 ml anhydrous THF solution containing magnesium powder (0.3 g, 12.5 mmol), and refluxed for 2 hr. After it was cooled, the clear reaction solution was added into carbon disulfide (1 ml, 16.8 mmol) at 0° C., and stirred for 30 min at rt. The resulting mixture was then added into methylhydrazine (1.6 ml, 30 mmol) at 0° C., and stirred for another 2 hours. To this solution was added water (15 ml) and extracted with EtOAc (30 ml×3). The organic solution was concentrated to minimum volume, and subjected to silica gel column chromatography (eluant: 1:3-1:1 ethyl acetate:hexanes) to give thiobenzoic acid N1-methyl hydrazide (0.72 g, total yield: 48%). 1H NMR (CDCl3) δ 3.3 (s, 3H), 6.0 (s, 2H), 7.3-7.4 (m, 5H); ESMS calcd (C8H10N2S): 166.1. found: 167.1 (M+H)+. refluxed for 2 hr After it was cooled stirred for another 2 hours extracted with EtOAc (30 ml×3) The organic solution was concentrated to minimum volume

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

実験手順: Bromobenzene (1.6 g, 10 mmol) was added into 25 ml anhydrous THF solution containing magnesium powder (0.3 g, 12.5 mmol), and refluxed for 2 hr. After it was cooled, the clear reaction solution was added into carbon disulfide (1 ml, 16.8 mmol) at 0° C., and stirred for 30 min at rt. The resulting mixture was then added into methylhydrazine (1.6 ml, 30 mmol) at 0° C., and stirred for another 2 hours. To this solution was added water (15 ml) and extracted with EtOAc (30 ml×3). The organic solution was concentrated to minimum volume, and subjected to silica gel column chromatography (eluant: 1:3-1:1 ethyl acetate: hexanes) to give thiobenzoic acid N-methyl hydrazide (0.72 g, total yield: 48%). 1H NMR (CDCl3) δ 3.3 (s, 3H), 6.0 (s, 2H), 7.3-7.4 (m, 5H); ESMS calcd (C8H10N2S): 166.1; found: 167.1 (M+H)+. refluxed for 2 hr After it was cooled stirred for another 2 hours extracted with EtOAc (30 ml×3) The organic solution was concentrated to minimum volume

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

実験手順: Bromobenzene (1.6 g, 10 mmol) was added into 25 ml anhydrous THF solution containing magnesium powder (0.3 g, 12.5 mmol), and refluxed for 2 hr. After it was cooled, the clear reaction solution was added into carbon disulfide (1 ml, 16.8 mmol) at 0° C., and stirred for 30 min at rt. The resulting mixture was then added into methylhydrazine (1.6 ml, 30 mmol) at 0° C., and stirred for another 2 hours. To this solution was added water (15 ml) and extracted with EtOAc (30 ml×3). The organic solution was concentrated to minimum volume, and subjected to silica gel column chromatography (eluant: 1:3-1:1 ethyl acetate: hexanes) to give thiobenzoic acid N-methyl hydrazide (0.72 g, total yield: 48%). 1H NMR (CDCl3) δ 3.3 (s, 3H), 6.0 (s, 2H), 7.3-7.4 (m, 5H); ESMS calcd (C8H10N2S): 166.1; found: 167.1 (M+H)+. refluxed for 2 hr After it was cooled stirred for another 2 hours extracted with EtOAc (30 ml×3) The organic solution was concentrated to minimum volume

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

実験手順: Bromobenzene (1.6 g, 10 mmol) was added into 25 ml anhydrous THF solution containing magnesium powder (0.3 g, 12.5 mmol), and refluxed for 2 hr. After it was cooled, the clear reaction solution was added into carbon disulfide (1 ml, 16.8 mmol) at 0° C., and stirred for 30 min at rt. The resulting mixture was then added into methylhydrazine (1.6 ml, 30 mmol) at 0° C., and stirred for another 2 hours. To this solution was added water (15 ml) and extracted with EtOAc (30 ml×3). The organic solution was concentrated to minimum volume, and subjected to silica gel column chromatography (eluant: 1:3-1:1 ethyl acetate:hexanes) to give thiobenzoic acid N1-methyl hydrazide (0.72 g, total yield: 48%). 1H NMR (CDCl3) δ 3.3 (s, 3H), 6.0 (s, 2H), 7.3-7.4 (m, 5H); ESMS calcd (C8H10N2S): 166.1. found: 167.1 (M+H)+. refluxed for 2 hr After it was cooled stirred for another 2 hours extracted with EtOAc (30 ml×3) The organic solution was concentrated to minimum volume

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

実験手順: To a 0° C. solution of N-methylbenzothiohydrazide (10 mmol) in DCM (20 mL) and pyridine (1 mL) was added 2-(chlorosulfonyl)acetyl chloride (5 mmol) dropwise. The mixture was kept at rt for 2 h before it was poured into water (20 ml). The organic layer was separated, dried and evaporated and the resulting residue was purified by column chromatography to give compound 68 as yellowish solids (0.8 g). 1H-NMR (CDCl3) δ 10.5 (m, 1H), 7.4 (m, 10H), 4.4 (m, 1H), 3.4-3.8 (m, 8H) ppm; ESMS calcd for C18H20N4O3S3:436.1; found: 437.2 (M+H+). The organic layer was separated dried evaporated the resulting residue was purified by column chromatography

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

実験手順: Bromobenzene (1.6 g, 10 mmol) was added into 25 ml anhydrous THF solution containing magnesium powder (0.3 g, 12.5 mmol), and refluxed for 2 hr. After it was cooled, the clear reaction solution was added into carbon disulfide (1 ml, 16.8 mmol) at 0° C., and stirred for 30 min at rt. The resulting mixture was then added into methylhydrazine (1.6 ml, 30 mmol) at 0° C., and stirred for another 2 hours. To this solution was added water (15 ml) and extracted with EtOAc (30 ml×3). The organic solution was concentrated to minimum volume, and subjected to silica gel column chromatography (eluant: 1:3–1:1 ethyl acetate: hexanes) to give thiobenzoic acid N1-methyl hydrazide (0.72 g, total yield: 48%). 1H NMR (CDCl3) δ 3.3 (s, 3H), 6.0 (s, 2H), 7.3–7.4 (m, 5H); ESMS calcd (C8H10N2S): 166.1; found: 167.1 (M+H)+. refluxed for 2 hr After it was cooled stirred for another 2 hours extracted with EtOAc (30 ml×3) The organic solution was concentrated to minimum volume

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

実験手順: Bromobenzene (1.6 g, 10 mmol) was added into 25 ml anhydrous THF solution containing magnesium powder (0.3 g, 12.5 mmol), and refluxed for 2 hr. After it was cooled, the clear reaction solution was added into carbon disulfide (1 ml, 16.8 mmol) at 0° C., and stirred for 30 min at rt. The resulting mixture was then added into methylhydrazine (1.6 ml, 30 mmol) at 0° C., and stirred for another 2 hours. To this solution was added water (15 ml) and extracted with EtOAc (30 ml×3). The organic solution was concentrated to minimum volume, and subjected to silica gel column chromatography (eluant: 1:3-1:1 ethyl acetate: hexanes) to give thiobenzoic acid N1-methyl hydrazide (0.72 g, total yield: 48%). 1H NMR (CDCl3) δ 3.3 (s, 3H), 6.0 (s, 2H), 7.3-7.4 (m, 5H); ESMS calcd (C8H10N2S): 166.1; found: 167.1 (M+H)+. refluxed for 2 hr After it was cooled stirred for another 2 hours extracted with EtOAc (30 ml×3) The organic solution was concentrated to minimum volume

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

実験手順: 44 mg (0.25 mmol) 2-(chlorosulfonyl)acetyl chloride dissolved in 1 ml dry THF was treated with 42 mg (0.25 mmol) N-methylbenzothiohydrazide dissolved in 0.5 ml THF at 0° C. over 15 min. The reaction was stirred for 15 min and then checked by TLC if the thiohydrazide has completely reacted. Now 40 mg (0.25 mmol) N,N-diethyl-1-methylhydrazinecarbothioamide dissolved in 0.5 ml THF was added and the mixture stirred at 0° C. for 15 min. Then 60 μl (0.75 mmol) pyridine was added and the reaction allowed to warm up to r.t. overnight. The reaction was quenched with 5 ml water, the pH adjusted to 11 and extracted with 5 ml ethyl acetate. The pH was reduced to 4-5 and the aqueous phase extracted 2 times with 5 ml ethyl acetate. The latter extracts were dried over MgSO4 and concentrated. If the purity was not satisfactory (<90%) it was purified on silica with DCM/MeOH (5-20%)/NH4OH (1%). ESMS (C16H25N5O3S3): calc'd. 431.11. Found: 432.2 [M+H+]. has completely reacted was added the mixture stirred at 0° C. for 15 min The reaction was quenched with 5 ml water extracted with 5 ml ethyl acetate the aqueous phase extracted 2 times with 5 ml ethyl acetate The latter extracts were dried over MgSO4 concentrated was purified on silica with DCM/MeOH (5-20%)/NH4OH (1%)