1-(2,5-dichlorophenyl)ethanone

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: A mixture of 31.0 g of 2',5'-dichloroacetophenone and 25 ml of N,N-dimethylformamide dimethyl acetal is heated on a steam bath for 6 hours, then evaporated to dryness in vacuo. The residue is slurried with hexane, and filtered to give 35.3 g of 2',5'-dichloro-3-dimethylaminoacrylophenone as orange crystals, mp 83°-85° C. is heated on a steam bath for 6 hours evaporated to dryness in vacuo filtered

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

Procedure: A mixture of 50.0 g of 2,5-dichloroacetophenone and 50 ml of N,N-dimethylacetamide dimethyl acetal was stirred and heated at reflux for 121/2 hours. The mixture was then cooled and evaporated in vacuo to give an oil which crystallized on scratching to give a dark red solid. This was collected and washed with hexane/ether to give 58.8 g of 1-(2,5-dichlorophenyl)-3-(dimethylamino)-2-buten-1-one as a red solid. heated at reflux for 121/2 hours The mixture was then cooled evaporated in vacuo to give an oil which crystallized to give a dark red solid This was collected washed with hexane/ether

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

Procedure: A mixture of 31.0 g of 2',5'-dichloroacetophenone and 25 ml of N,N-dimethylformamide dimethyl acetal was heated on a steam bath for 6 hours, then evaporated to dryness in vacuo. The residue was slurried with hexane, filtered, and gave 35.3 g of 2',5'-dichloro-3-dimethylaminoacrylophenone as orange crystals, mp 83°-85° C. was heated on a steam bath for 6 hours evaporated to dryness in vacuo filtered

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

Procedure: A suspension of mossy zinc (10 g) and mercuric chloride (0.5 g) in coned HCl (0.5 mL) and water (5 mL) was shaken for 5 min. The aqueous layer was then decanted. To the residue was added concd HCl (7.5 mL) and water (7.5 mL) followed by 2′,5′-dichloroacetophenone (3.106 g, 16.43 mmol) and the suspension was refluxed for 4 h during which time, hourly addition of coned HCl (90.5 mL) was carried out. The resulting suspension was cooled to room temperature and the aqueous layer was decanted. The residual solid was washed with ether (3×30 mL). The aqueous layer was extracted with ether (3×50 mL). The combined ether layer was washed with brine, dried over anhydrous Na2SO4, and removed under vacuum. The residue was dried further under vacuum to obtain 2.664 g crude product, which was purified on silica gel (Texane) to obtain 0.813 g (28%) pure (1H NMR) title compound as a colorless liquid; 1H NMR (DMSO-d6) 1.23 (t, 3H, J=7.5 Hz), 2.73 (q, 2H, J=7.5 Hz), 7.09-7.27 (m, 3H). The aqueous layer was then decanted To the residue was added concd HCl (7.5 mL) and water (7.5 mL) the aqueous layer was decanted The residual solid was washed with ether (3×30 mL) The aqueous layer was extracted with ether (3×50 mL) The combined ether layer was washed with brine dried over anhydrous Na2SO4 removed under vacuum The residue was dried further under vacuum to obtain 2.664 g crude product, which was purified on silica gel (Texane)

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-(2,5-Dichlorophenyl)ethanone (20 mg, 0.106 mmol) and 3-(morpholinosulfonyl)benzohydrazide (30.2 mg, 0.106 mmol) were dissolved in methanol (4 mL) in the presence of acetic acid as a catalyst, and the reaction mixture was heated via microwave irradiation to 120° C. for 30 min. Following cooling, the solvent was removed by vacuum and the resulting crude material was purified by flash column chromatography affording the title compound in a 10 mg yield. 1H NMR (400 MHz, CDCl3): δ 8.29 (m, 1H), 8.09 (m, 1H), 7.81 (m, 1H), 7.57 (m, 1H), 7.40 (m, 1H), 7.26 (m, 2H), 3.52 (m, 4H), 2.91 (m, 4H), 2.28 (s, 3H). ESI-MS: 456.1 [M+H]+. Following cooling the solvent was removed by vacuum the resulting crude material was purified by flash column chromatography

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-(2,5-Dichlorophenyl)ethanone (20 mg, 0.106 mmol) and 3-(morpholinosulfonyl)benzohydrazide (30.2 mg, 0.106 mmol) were dissolved in methanol (4 mL) in the presence of acetic acid as a catalyst, and the reaction mixture was heated via microwave irradiation to 120° C. for 30 min. Following cooling, the solvent was removed by vacuum and the resulting crude material was purified by flash column chromatography affording the title compound in a 10 mg yield. 1H NMR (400 MHz, CDCl3): δ 8.29 (m, 1H), 8.09 (m, 1H), 7.81 (m, 1H), 7.57 (m, 1H), 7.40 (m, 1H), 7.26 (m, 2H), 3.52 (m, 4H), 2.91 (m, 4H), 2.28 (s, 3H). ESI-MS: 456.1 [M+H]+. Following cooling the solvent was removed by vacuum the resulting crude material was purified by flash column chromatography

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

Procedure: To 2,5-dichloroacetophenone (5.0 g, 26.45 mmol) in anhydrous tetrahydrofuran (53 mL) under argon was added phenyltrimethylammonium tribromide (9.94 g, 26.45 mmol, 1.0 eq) at 0° C. The reaction mixture was stirred at ambient temperature for 16 h, concentrated, and re-dissolved in ethyl acetate. The organic layer was washed with water (2×250 mL) and brine (1×150 mL), dried (MgSO4), filtered, and evaporated in vacuo. Purification using MPLC chromatography (Biotage) gave 3.47 g (52.5%) of 2-bromo-1-(2,5-dichlorophenyl)ethanone as a clear oil. 1H-NMR (DMSO-d6) δ 7.93 (dd, J=2.1 Hz, 0.9 Hz, 1H), 7.61 to 7.60 (m, 2H), 4.86 (s, 2H); concentrated re-dissolved in ethyl acetate The organic layer was washed with water (2×250 mL) and brine (1×150 mL) dried (MgSO4) filtered evaporated in vacuo Purification

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

Procedure: To 2,5-dichloroacetophenone (5.0 g, 26.45 mmol) in anhydrous tetrahydrofuran (53 mL) under argon was added phenyltrimethylammonium tribromide (9.94 g, 26.45 mmol, 1.0 eq) at 0° C. The reaction mixture was stirred at ambient temperature for 16 h, concentrated, and re-dissolved in ethyl acetate. The organic layer was washed with water (2×250 mL) and brine (1×150 mL), dried (MgSO4), filtered, and evaporated in vacuo. Purification using MPLC chromatography (Biotage) gave 3.47 g (52.5%) of 2-bromo-1-(2,5-dichlorophenyl)ethanone as a clear oil. 1H-NMR (DMSO-d6) δ 7.93 (dd, J=2.1 Hz, 0.9 Hz, 1H), 7.61 to 7.60 (m, 2H), 4.86 (s, 2H); concentrated re-dissolved in ethyl acetate The organic layer was washed with water (2×250 mL) and brine (1×150 mL) dried (MgSO4) filtered evaporated in vacuo Purification

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,5-Dichloroacetophenone (20.9 g, 0.11 mol) was dissolved in diethyl ether (300 mL) and the reaction mixture was cooled to 0° C. Bromine (5.66 mL, 0.11 mol) was added slowly dropwise and the reaction mixture was allowed to warm to room temperature over 20 minutes. The reaction mixture was treated with saturated aqueous NaHCO3 solution (250 mL). The organic layer was separated, dried over MgSO4 and concentrated in vacuo, yielding the title compound (20.0 g, 68%) as a yellow oil. δH (d6-DMSO) 7.94 (dd, J 2.2, 0.3 Hz, 1H), 7.61 (m, 2H), 4.88 (s, 2H). to warm to room temperature over 20 minutes The organic layer was separated dried over MgSO4 concentrated in vacuo

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

Procedure: To an ice-cooled solution of 2′,5′-dichloroacetophenone (1.0 g, 5.0 mmol) in acetic acid (10 mL) was added HBr (˜1%) followed by a solution of bromine (0.80 g, 5.0 mmol) in acetic acid (3 mL). The resultant mixture was warmed to room temperature and stirred overnight. The mixture was poured into ice water and then neutralized with saturated aqueous sodium carbonate solution. Saturated aqueous sodium thiosulfate solution was then added to the mixture. The resultant mixture was extracted with ethyl acetate. The organic phase was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated. Purification by flash column chromatography afforded 2-bromo-1-(2,5-dichlorophenyl)ethanone as an oil (0.70 g, 50% yield). 1H NMR (400 MHz, CDCl3): 7.54 (d, J=2.4 Hz, 1H), 7.43 (m, 1H), 7.40 (m, 1H), 4.68 (s, 2H). The resultant mixture was extracted with ethyl acetate The organic phase was washed with saturated aqueous sodium chloride solution dried over anhydrous sodium sulfate filtered concentrated Purification by flash column chromatography