2-bromocyclohexane-1,3-dione

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 2-bromocyclohexane-1,3-dione (8 g, 42 mmol) in pyridine (50 mL), was added thioacetamide (3.2 g, 42.5 mmol). The reaction mixture was heated at 100° C. for 16 hours. The solvent was then removed under reduced pressure the residue poured in water (250 mL). The reaction mixture was extracted with dichloromethane (3×100 mL). The organic extract was dried using anhydrous sodium sulfate, concentrated under reduced pressure. The crude product was purified by flash column chromatography (Silica gel, gradient from 100% dichloromethane to 2% methanol in dichloromethane) to give the pure desired product (3 g, 42%) as a solid. 1H NMR (CDCl3, 400 MHz): δ 3.01 (t, J=6.0 Hz, 2H), 2.74 (s, 3H), 2.60 (t, J=4 Hz, 2H), 2.20 (quintet, J=4 Hz, 2H); LCMS [M+H]: 168. The solvent was then removed under reduced pressure the residue poured in water (250 mL) The reaction mixture was extracted with dichloromethane (3×100 mL) The organic extract was dried concentrated under reduced pressure The crude product was purified by flash column chromatography (Silica gel, gradient from 100% dichloromethane to 2% methanol in dichloromethane)

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

Procedure: To a stirred solution of 1,3 Cyclohexandione (10 g, 89 mmol) in dichloromethane (22 mL) at 0° C. was added a solution of bromine (3.8 mL, 89 mmol) in dichloromethane (3 mL) over a period of 10 minutes. The reaction mixture was stirred at room temperature for 1.5 hours. The reaction mixture was filtered and the residue washed with hexane (200 mL). The residue was taken into water (75 mL) and heated at 80° C. for 30 minutes. It was cooled to room temperature, filtered and dried under reduced pressure to give the desired product (14 g, 82%) as a solid. ESMS [M+H]: 191. The reaction mixture was filtered the residue washed with hexane (200 mL) heated at 80° C. for 30 minutes It was cooled to room temperature filtered dried under reduced pressure

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

Procedure: To a stirred solution of 1,3 Cyclohexandione (10 g, 89 mmol) in dichloromethane (22 mL) at 0° C. was added a solution of bromine (3.8 mL, 89 mmol) in dichloromethane (3 mL) over a period of 10 minutes. The reaction mixture was stirred at room temperature for 1.5 hours. The reaction mixture was filtered and the residue washed with hexane (200 mL). The residue was taken into water (75 mL) and heated at 80° C. for 30 minutes. It was cooled to room temperature, filtered and dried under reduced pressure to give the desired product (14 g, 82%) as a solid. ESMS [M+H]: 191. The reaction mixture was filtered the residue washed with hexane (200 mL) heated at 80° C. for 30 minutes It was cooled to room temperature filtered dried under reduced pressure

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

Procedure: To a stirred solution of 1,3 Cyclohexandione (10 g, 89 mmol) in dichloromethane (22 mL) at 0° C. was added a solution of bromine (3.8 mL, 89 mmol) in dichloromethane (3 mL) over a period of 10 minutes. The reaction mixture was stirred at room temperature for 1.5 hours. The reaction mixture was filtered and the residue washed with hexane (200 mL). The residue was taken into water (75 mL) and heated at 80° C. for 30 minutes. It was cooled to room temperature, filtered and dried under reduced pressure to give the desired product (14 g, 82%) as a solid. ESMS [M+H]: 191. The reaction mixture was filtered the residue washed with hexane (200 mL) heated at 80° C. for 30 minutes It was cooled to room temperature filtered dried under reduced pressure

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

Procedure: To a solution of ethanethioamide (0.75 g, 10 mmol) in ethanol (20 mL) at room temperature was added 2-bromocyclohexane-1,3-dione (1.9 g, 10 mmol) in portions. The reaction solution was refluxed for 2 hours while stirring. After removal of solvents, the residue was diluted with water and washed with diethyl ether. The separated aqueous layer was basified with sodium carbonate solution. The resulting solid was collected by vacuum filtration, rinsed with water. The solid was suspended in methanol and followed by evaporation to dryness to produce the title compound. The reaction solution was refluxed for 2 hours After removal of solvents the residue was diluted with water washed with diethyl ether The resulting solid was collected by vacuum filtration rinsed with water followed by evaporation to dryness

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

Procedure: Cyclohexane-1,3-dione (11.2 g, 0.1 mol) was suspended in ice water (70 mL) and bromine (5.16 mL, 0.1 mol) was added dropwise over 5 minutes. The resulting suspension was stirred at room temperature for 3 hours. The suspension was filtered and the solid was stirred in water (200 mL) for 30 minutes. The solid was collected by vacuum filtration, rinsed with water, and dried to render crude product. The crude product was recrystallized from ethanol to produce the title compound. The suspension was filtered the solid was stirred in water (200 mL) for 30 minutes The solid was collected by vacuum filtration rinsed with water dried The crude product was recrystallized from ethanol

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

Procedure: A solution of 2-bromo-cyclohexane-1,3-dione (8.0 g, 41.9 mmol) and methyl thiourea (3.77 g, 41.9 mmol) in pyridine (63 mL) was stirred at room temperature for 16 h. The reaction mixture was concentrated under vacuum, extracted with CH2Cl2 /10% aq NaCl solution, dried, filtered, and concentrated under vacuum. Crystallization from EtOAc afforded the title compound as yellow crystals (3.26 g, 43%): mp 180-182° C. Anal. RP-HPLC: tR 8.4 min (0-60% MeCN, purity 100%). 1H-NMR (CDCl3): δ 7.90 (s, 1H, NH), 2.99 (s, 3H, CH3), 2.72 (t, 2H, J 6.1, CH2), 2.49 (t, 2H, J 6.1, CH2), 2.10 (qu, 2H, J 6.1, CH2). 13C-NMR (CDCl3): δ 191.0, 176.6, 168.0, 120.0, 37.5, 32.5, 27.7, 23.2. MS: (ESI+) m/z 183.07 (M+H)+. The reaction mixture was concentrated under vacuum extracted with CH2Cl2 /10% aq NaCl solution dried filtered concentrated under vacuum Crystallization from EtOAc

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: w To a solution of 2-bromo-cyclohexane-1,3-dione (20 g, 0.105 mol) in pyridine (150 mL) was added thioacetamide (7.9 g, 0.105 mol) and the mixture was stirred at 50° C. After 16 h the solvent was removed under vacuum. 10% aq NaCl solution (150 mL) was added and the product was extracted with CH2Cl2 (4×100 mL). The organic extracts were washed with additional 10% aq NaCl solution (2×100 mL) before being dried, filtered, and concentrated under vacuum. The dark viscous oil obtained was purified using a Kugelrohr distillation unit to afford the product as a yellow oil (6.97 g, 40%): 1H-NMR (CDCl3): δ 3.02 (t, 2H, J 6.1, CH2), 2.75 (s, 3H, CH3), 2.61 (t, 2H, J 6.1, CH2), 2.21 (qu, 2H, J 6.1, CH2). 13C-NMR (CDCl3): δ 192.1, 173.3, 166.8, 130.9, 37.8, 27.1, 23.1, 20.0. MS (ESI+): m/z 168.03 (M+H)+. After 16 h the solvent was removed under vacuum 10% aq NaCl solution (150 mL) was added the product was extracted with CH2Cl2 (4×100 mL) The organic extracts were washed with additional 10% aq NaCl solution (2×100 mL) before being dried filtered concentrated under vacuum The dark viscous oil obtained was purified a Kugelrohr distillation unit

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

Procedure: A solution of 1,3-cyclohexanedione (50 g, 0.45 mol) in CH2Cl2 (111 mL) was stirred at 5° C. Bromine (18 mL, 56.3 g, 0.35 mol) in CH2Cl2 (17 mL) was added dropwise over a period of 5-10 min. The reaction mixture was stirred at room temperature for 1 h. The brown precipitate that formed was collected by filtration, washed with CH2Cl2/toluene (100 mL), and air dried, before being crystallized from H2O to afford the title compound as pale yellow crystals (42.6 g, 50%): mp 167-168° C. Anal. RP-HPLC: tR 7.9 min (0-60% MeCN, purity 100%). 1H-NMR (DMSO-d6): δ 2.49 (t, 4H, J 6.1, 2×CH2), 1.85 (qu, 2H, J 6.1, CH2). MS (ESI−): m/z 190.90/188.90 (M-H)+. The brown precipitate that formed was collected by filtration washed with CH2Cl2/toluene (100 mL), and air dried before being crystallized from H2O

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

Procedure: To a stirred solution of cyclohexane-1,3-dione (1.12 g, 10 mmol) in AcOH (20 mL) at r.t. was added bromine (1.6 g, 0.51 mL, 10 mmol) dropwise. The reaction mixture was stirred for 2 h and then the product was isolated by filtration. The precipitate was washed twice with Et2O (100 mL) and then dried in vacuo to give the title compound in quantitative yield as a buff solid, which was used without further purification. LCMS (ES+) 190.9 (M+H)+. the product was isolated by filtration The precipitate was washed twice with Et2O (100 mL) dried in vacuo