2-hydroxybenzenecarbothioamide

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: A stirred solution of 2-hydroxybenzenecarbothioamide 3a (5.36 g, 35.0 mmol), ethyl 4-chloroacetoacetate (6.34 g, 38.5 mmol) in dry THF (70 mL) was heated to reflux under nitrogen for 2.5 days. At ambient temperature, the mixture was diluted with EtOAc (200 mL), then cautiously treated with saturated aq. NaHCO3 (40 mL), and followed by adding solid NaHCO3 in small portions until CO2 evolution ceased. The organic layer was separated, washed with brine (40 mL×2), dried over MgSO4, and filtered. After concentration in vacuo, the oily residue was chromatographed on silica gel (gradient EtOAc/CH2Cl2 : 0-4%) to provide 4a (8.53 g, 93%) as a white solid, which was recrystallized from toluene/hexane at -30° C. mp 35.5°-36.5° C.; IR (neat) 3120, 1740, 1480, 1225 cm-1 ; 1H NMR (DMSO-d6) δ 1.15 (3H, t, J=7.1 Hz, CH3), 3.84 (2H, s, CH2), 4.07 (2H, q, J=7.1 Hz, CH2), 6.89 (1H, t, J=7.8 Hz, Ar), 6.97 (1H, d, J=7.8 Hz, Ar), 7.26 (1H, t, J=7.8 Hz, Ar), 7.48 (1H, s), 7.93 (1H, d, J=7.8 Hz, Ar), 11.29 (1H, s, OH); FABMS m/z 263 (M+), 264 (M++1); Anal. Calcd for C13H13NO3S: C, 59.30; H, 4.98; N, 5.32. Found: C, 59.16; H, 4.97; N, 5.50. to reflux under nitrogen for 2.5 days The organic layer was separated washed with brine (40 mL×2) dried over MgSO4 filtered After concentration in vacuo the oily residue was chromatographed on silica gel (gradient EtOAc/CH2Cl2 : 0-4%)

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

実験手順: A stirred solution of 2-hydroxybenzenecarbothioamide 3a (5.36 g, 35.0 mmol), ethyl 4-chloroacetoacetate (6.34 g, 38.5 mmol) in dry THF (70 mL) was heated to reflux under nitrogen for 2.5 days. At ambient temperature, the mixture was diluted with EtOAc (200 mL), then cautiously treated with saturated aq. NaHCO3 (40 mL), and followed by adding solid NaHCO3 in small portions until CO2 evolution ceased. The organic layer was separated, washed with brine (40 mL×2), dried over MgSO4, and filtered. After concentration in vacuo, the oily residue was chromatographed on silica gel (gradient EtOAc/CH2Cl2 : 0-4%) to provide 4a (8.53 g, 93%) as a white solid, which was recrystallized from toluene/hexane at -30° C. mp 35.5°-36.5° C.; IR (neat) 3120, 1740, 1480, 1225 cm-1 ; 1H NMR (DMSO-d6) δ 1.15 (3H, t, J=7.1 Hz, CH3), 3.84 (2H, s, CH2), 4.07 (2H, q, J=7.1 Hz, CH2), 6.89 (1H, t, J=7.8 Hz, Ar), 6.97 (1H, d, J=7.8 Hz, Ar), 7.26 (1H, t, J=7.8 Hz, Ar), 7.48 (1H, s), 7.93 (1H, d, J=7.8 Hz, Ar), 11.29 (1H, s, OH); FABMS m/z 263 (M+), 264 (M++1); Anal. Calcd for C13H13NO3S: C, 59.30; H, 4.98; N, 5.32. Found: C, 59.16; H, 4.97; N, 5.50. to reflux under nitrogen for 2.5 days The organic layer was separated washed with brine (40 mL×2) dried over MgSO4 filtered After concentration in vacuo the oily residue was chromatographed on silica gel (gradient EtOAc/CH2Cl2 : 0-4%)

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

実験手順: The procedure used for the preparation of 3a was repeated with 3-hydroxybenzonitrile (5.48 g, 46.1 mmol), (EtO)2P(S)SH (7.72 mL, 46.1 mmol) and water (9.2 mL) at 80° C. for 36 hr to give 3d (4.04 g, 57%) as a yellow solid after chromatographic purification on silica gel (gradient EtOAc/CH2Cl2 : 6-12%) and crystallization from EtOAc/hexane. mp 139.0°-140.0° C.; IR (KBr) 3340, 3280, 3165, 1629, 1590, 1462 cm-1 ; 1H NMR (DMSO-d6) δ 6.83 (1H, br d, J=7.0 Hz, Ar), 7.10-7.25 (2H, m, Ar), 7.27 (1H, s, Ar), 9.33 (1H, br s, NH), 9.58 (1H, s, OH), 9.72 (1H, br s, NH); FDMS m/z 153 (M+); Anal. Calcd for C7H7NOS: C, 54.88; H, 4.60; N, 9.14. Found: C, 55.01; H, 4.53; N, 9.02.

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

実験手順: The procedure used for the preparation of 3a was repeated with 3-hydroxybenzonitrile (5.48 g, 46.1 mmol), (EtO)2P(S)SH (7.72 mL, 46.1 mmol) and water (9.2 mL) at 80° C. for 36 hr to give 3d (4.04 g, 57%) as a yellow solid after chromatographic purification on silica gel (gradient EtOAc/CH2Cl2 : 6-12%) and crystallization from EtOAc/hexane. mp 139.0°-140.0° C.; IR (KBr) 3340, 3280, 3165, 1629, 1590, 1462 cm-1 ; 1H NMR (DMSO-d6) δ 6.83 (1H, br d, J=7.0 Hz, Ar), 7.10-7.25 (2H, m, Ar), 7.27 (1H, s, Ar), 9.33 (1H, br s, NH), 9.58 (1H, s, OH), 9.72 (1H, br s, NH); FDMS m/z 153 (M+); Anal. Calcd for C7H7NOS: C, 54.88; H, 4.60; N, 9.14. Found: C, 55.01; H, 4.53; N, 9.02.

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

実験手順: The procedure used for the preparation of 3a was repeated with 2,6-dihydroxybenzonitrile (8.75 g, 64.8 mmol), (EtO)2P(S)SH (32.6 mL, 194 mmol) and water (26 mL) at 60° C. for 36 hr to give 3b (4.76 g, 43%) as a light yellow solid after chromatographic purification on silica gel (gradient EtOAc/CH2Cl2 : 0-5%) and crystallization from EtOAc/hexane. mp 180° C. (dec); IR (KBr) 3411, 3295, 3177, 2380, 1612, 1577, 1464, 1267, 1010 cm-1 ; 1H NMR (DMSO-d6) δ 6.31 (2H, d, J=8.1 Hz, Ar), 7.00 (1H, t, J=8.1Hz, Ar), 9.60 (1H, br s, NH), 9.96 (1H, br s, NH), 10.93 (2H, s, OH); FABMS m/z 169 (M+), 170 (M+ +1); Anal. Calcd for C7H7NO2S: C, 49.69; H, 4.17; N, 8.28. Found: C, 49.89; H, 403; N, 8.36.

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

実験手順: The procedure used for the preparation of 3a was repeated with 2,6-dihydroxybenzonitrile (8.75 g, 64.8 mmol), (EtO)2P(S)SH (32.6 mL, 194 mmol) and water (26 mL) at 60° C. for 36 hr to give 3b (4.76 g, 43%) as a light yellow solid after chromatographic purification on silica gel (gradient EtOAc/CH2Cl2 : 0-5%) and crystallization from EtOAc/hexane. mp 180° C. (dec); IR (KBr) 3411, 3295, 3177, 2380, 1612, 1577, 1464, 1267, 1010 cm-1 ; 1H NMR (DMSO-d6) δ 6.31 (2H, d, J=8.1 Hz, Ar), 7.00 (1H, t, J=8.1Hz, Ar), 9.60 (1H, br s, NH), 9.96 (1H, br s, NH), 10.93 (2H, s, OH); FABMS m/z 169 (M+), 170 (M+ +1); Anal. Calcd for C7H7NO2S: C, 49.69; H, 4.17; N, 8.28. Found: C, 49.89; H, 403; N, 8.36.

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

実験手順: A stirred solution of 2-hydroxybenzonitrile (23.8 g, 200 mmol), (EtO)2P(S)SH (33.6 mL, 200 mmol) and water (40 mL) was heated at 80° C. for 12 hr under nitrogen. The mixture was cooled down to 0°-10° C., diluted with CH2Cl2 (200 mL)/Et2O (400 mL), then cautiously treated with saturated aq. NaHCO3 (60 mL), and followed by adding solid NaHCO3 in small portions until CO2 evolution ceased. Half-saturated aq. NaCl (40 mL) was added to the mixture. The organic layer was separated, washed with brine (100 mL), dried over MgSO4, and filtered. After concentration in vacuo, the residue was chromatographed on silica gel (gradient EtOAc/CH2Cl2 : 0-5%) to give 3a (16.7 g, 55%) as a pinkish solid, which had the same 1H NMR data as reported in the literature (Yousif, N. M. Tetrahedron 1989, 45, 4599). The mixture was cooled down to 0°-10° C. The organic layer was separated washed with brine (100 mL) dried over MgSO4 filtered After concentration in vacuo the residue was chromatographed on silica gel (gradient EtOAc/CH2Cl2 : 0-5%)

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

実験手順: A stirred solution of 2-hydroxybenzonitrile (23.8 g, 200 mmol), (EtO)2P(S)SH (33.6 mL, 200 mmol) and water (40 mL) was heated at 80° C. for 12 hr under nitrogen. The mixture was cooled down to 0°-10° C., diluted with CH2Cl2 (200 mL)/Et2O (400 mL), then cautiously treated with saturated aq. NaHCO3 (60 mL), and followed by adding solid NaHCO3 in small portions until CO2 evolution ceased. Half-saturated aq. NaCl (40 mL) was added to the mixture. The organic layer was separated, washed with brine (100 mL), dried over MgSO4, and filtered. After concentration in vacuo, the residue was chromatographed on silica gel (gradient EtOAc/CH2Cl2 : 0-5%) to give 3a (16.7 g, 55%) as a pinkish solid, which had the same 1H NMR data as reported in the literature (Yousif, N. M. Tetrahedron 1989, 45, 4599). The mixture was cooled down to 0°-10° C. The organic layer was separated washed with brine (100 mL) dried over MgSO4 filtered After concentration in vacuo the residue was chromatographed on silica gel (gradient EtOAc/CH2Cl2 : 0-5%)

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

実験手順: A stirred solution of 2-hydroxybenzenecarbothioamide 3a (5.36 g, 35.0 mmol), ethyl 4-chloroacetoacetate (6.34 g, 38.5 mmol) in dry THF (70 mL) was heated to reflux under nitrogen for 2.5 days. At ambient temperature, the mixture was diluted with EtOAc (200 mL), then cautiously treated with saturated aq. NaHCO3 (40 mL), and followed by adding solid NaHCO3 in small portions until CO2 evolution ceased. The organic layer was separated, washed with brine (40 mL×2), dried over MgSO4, and filtered. After concentration in vacuo, the oily residue was chromatographed on silica gel (gradient EtOAc/CH2Cl2 : 0-4%) to provide 4a (8.53 g, 93%) as a white solid, which was recrystallized from toluene/hexane at -30° C. mp 35.5°-36.5° C.; IR (neat) 3120, 1740, 1480, 1225 cm-1 ; 1H NMR (DMSO-d6) δ1.15 (3H, t, J=7.1 Hz, CH3), 3.84 (2H, s, CH2), 4.07 (2H, q, J=7.1 Hz, CH2), 6.89 (1H, t, J=7.8 Hz, Ar), 6.97 (1H, d, J=7.8 Hz, Ar), 7.26 (1H, t, J=7.8 Hz, Ar), 7.48 (1H, s), 7.93 (1H, d, J=7.8 Hz, Ar), 11.29 (1H, s, OH); FABMS m/z 263 (M+), 264 (M+ +1); Anal. Calcd for C13H13NO3S: C, 59.30; H, 4.98; N, 5.32. Found: C, 59.16; H, 4.97; N, 5.50. to reflux under nitrogen for 2.5 days The organic layer was separated washed with brine (40 mL×2) dried over MgSO4 filtered After concentration in vacuo the oily residue was chromatographed on silica gel (gradient EtOAc/CH2Cl2 : 0-4%)

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

実験手順: A stirred solution of 2-hydroxybenzenecarbothioamide 3a (5.36 g, 35.0 mmol), ethyl 4-chloroacetoacetate (6.34 g, 38.5 mmol) in dry THF (70 mL) was heated to reflux under nitrogen for 2.5 days. At ambient temperature, the mixture was diluted with EtOAc (200 mL), then cautiously treated with saturated aq. NaHCO3 (40 mL), and followed by adding solid NaHCO3 in small portions until CO2 evolution ceased. The organic layer was separated, washed with brine (40 mL×2), dried over MgSO4, and filtered. After concentration in vacuo, the oily residue was chromatographed on silica gel (gradient EtOAc/CH2Cl2 : 0-4%) to provide 4a (8.53 g, 93%) as a white solid, which was recrystallized from toluene/hexane at -30° C. mp 35.5°-36.5° C.; IR (neat) 3120, 1740, 1480, 1225 cm-1 ; 1H NMR (DMSO-d6) δ1.15 (3H, t, J=7.1 Hz, CH3), 3.84 (2H, s, CH2), 4.07 (2H, q, J=7.1 Hz, CH2), 6.89 (1H, t, J=7.8 Hz, Ar), 6.97 (1H, d, J=7.8 Hz, Ar), 7.26 (1H, t, J=7.8 Hz, Ar), 7.48 (1H, s), 7.93 (1H, d, J=7.8 Hz, Ar), 11.29 (1H, s, OH); FABMS m/z 263 (M+), 264 (M+ +1); Anal. Calcd for C13H13NO3S: C, 59.30; H, 4.98; N, 5.32. Found: C, 59.16; H, 4.97; N, 5.50. to reflux under nitrogen for 2.5 days The organic layer was separated washed with brine (40 mL×2) dried over MgSO4 filtered After concentration in vacuo the oily residue was chromatographed on silica gel (gradient EtOAc/CH2Cl2 : 0-4%)

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

実験手順: The procedure used for the preparation of 3a was repeated with 3-hydroxybenzonitrile (5.48 g, 46.1 mmol), (EtO)2P(S)SH (7.72 mL, 46.1 mmol) and water (9.2 mL) at 80° C. for 36 hr to give 3d (4.04 g, 57%) as a yellow solid after chromatographic purification on silica gel (gradient EtOAc/CH2Cl2 : 6-12%) and crystallization from EtOAc/hexane. mp 139.0°-140.0° C.; IR (KBr) 3340, 3280, 3165, 1629, 1590, 1462 cm-1 ; 1H NMR (DMSO-d6) δ6.83 (1H, br d, J=7.0 Hz, Ar), 7.10-7.25 (2H, m, Ar), 7.27 (1H, s, Ar), 9.33 (1H, br s, NH), 9.58 (1H, s, OH), 9.72 (1H, br s, NH); FDMS m/z 153 (M+); Anal. Calcd for C7H7NOS: C, 54.88; H, 4.60; N, 9.14. Found: C, 55.01; H, 4.53; N, 9.02.