1,3,5-tribromobenzene

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

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

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

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

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

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

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of benzyl alcohol (10.8 g, 100 mmol) in dry DMF (40 mL), 60% NaH (4.4 g, 110 mmol) was added portionwise and the mixture was stirred at 55° C. for 10 min. Then, 1,3,5-tribromobenzene (22.0 g, 70 mmol) was added slowly to the reaction mixture and the resulting solution was heated at 120° C. for 4 h. After cooling to room temperature, the reaction mixture was poured into a mixture of diethyl ether (500 mL) and water (200 mL) along with intense stirring. The organic layer was separated and washed with water (2×100 mL), 5% HCl (100 mL), saturated NaHCO3 aqueous solution (100 mL) and brine (100 mL). The organic phase was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica using hexanes-acetone (10:0.5) as eluent to afford 18.5 g (77%) of title compound as an yellow oil. 1H NMR (CDCl3, 300 MHz): δ 7.45-7.32 (m, 5H); 7.25 (s, 1H); 7.07 (s, 2H); 5.05 (s, 2H). the resulting solution was heated at 120° C. for 4 h After cooling to room temperature The organic layer was separated washed with water (2×100 mL), 5% HCl (100 mL), saturated NaHCO3 aqueous solution (100 mL) and brine (100 mL) The organic phase was dried over magnesium sulfate filtered concentrated under reduced pressure The residue was purified by column chromatography on silica

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1,3,5-Tribromobenzene (125 g, 0.4 mol), was dissolved in anhydrous diethylether (1 L), and cooled to −70° C. n-Butyllithium (250 mL, 1.6 M in hexanes, 0.4 mol) was added dropwise over a one-hour period keeping the temperature near −70° C. The solution was stirred for an additional 20 minutes at −70° C. and then warmed to −10° C. over a two-hour period. The solution was then recooled to −70° C. and trimethylchlorosilane (45 g, 0.4 mol) was added over a one hour period. The solution was allowed to stir and warm to room temperature overnight. The solution was cooled to −70° C. and an additional 0.4 mol n-butyl lithium was added over a one-hour period. The resulting slurry was stirred for one hour at −70° C., warmed to −10° C. over a two-hour period and then recooled to −70° C. An additional 0.4 mol of trimethylchlorosilane was added and the slurry was allowed to warm to room temperature overnight. The mixture was quenched with water and the layers were separated. The organic layer was washed twice with sodium bicarbonate solution and with salt brine then dried over magnesium sulfate. The solvents were evaporated under vacuum and the product distilled twice under vacuum to yield 85.2 g (70%) of a colorless liquid. b.p. 100-105° C. @ 0.5 mmHg. was added dropwise over a one-hour period near −70° C warmed to −10° C. over a two-hour period was then recooled to −70° C. to stir warm to room temperature overnight The solution was cooled to −70° C. The resulting slurry was stirred for one hour at −70° C. warmed to −10° C. over a two-hour period recooled to −70° C to warm to room temperature overnight The mixture was quenched with water the layers were separated The organic layer was washed twice with sodium bicarbonate solution and with salt brine then dried over magnesium sulfate The solvents were evaporated under vacuum the product distilled twice under vacuum

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

Procedure: General procedure described for compounds 1 and 2 starting from 1,3,5-tribromobenzene and bromoacetyl bromide. Purified by column chromatography column (hexane:ethyl acetate 6:1), yield 45% m.p.: 86-87° C., 1H-NMR (CDCl3): δ7.7 (s, 2H, Ar), 4.44 (s, 2H, CH2); 13C-NMR (CDCl3): δ193.4 (CO), 139.4 (C—CO), 134.5 (CH), 124.7 (C—Br), 119.4 (C—Br), 34.6 (CH2); M/z (EI): 440, 438, 436, 434, 432 (M+, 1, 3, 5, 3, 1%), 345, 343, 341, 339 (M-CH2Br, 35, 96, 100, 41%); HPLC: Column μ Bondapack C18, 5 μm, 300 A, (300×3.9 mm), Purity 98%, r.t.=3.40 min, acetonitrile/H2O (0.05% H3PO4+0.04% Et3N) 50/50. Purified by column chromatography column (hexane:ethyl acetate 6:1), yield 45% m.p.: 86-87° C., 1H-NMR (CDCl3): δ7.7 (s, 2H, Ar), 4.44 (s, 2H, CH2) Column μ Bondapack C18, 5 μm, 300 A, (300×3.9 mm), Purity 98%, r.t.=3.40 min, acetonitrile/H2O (0.05% H3PO4+0.04% Et3N) 50/50

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

Procedure: To a solution of 12.6 g (40.0 mmol) of 1,3,5-tribromobenzene in 400 ml of ether, 160 ml (40.0 mmol) of 0.25 M nBuLi in hexanes was added for 1 h at −80° C. The mixture was stirred for 1.5 h at this temperature, and then a solution of 5.29 g (40.0 mmol) of indanone-2 in 200 ml of ether was added dropwise over 1 hour while vigorously stirring. The reaction mixture was allowed to warm to room temperature and it was stirred at this temperature for 24 h. Then, 100 ml of water was added. The organic layer was separated; the aqueous layer was extracted with 3×50 ml of dichloromethane. The combined organic layers were dried over Na2SO4 and then evaporated to dryness. The residue was dissolved in 250 ml of toluene, and 0.75 g of p-TosOH was added. The resulting solution was refluxed for 1 hours using a Dean-Stark trap to remove the water formed. Next, the mixture was evaporated to dryness, and the product was isolated by flash-chromatography on Silica Gel 60 (d 50 mm, l 400 mm, eluent: hexanes). Yield 8.54 g (61%) of white powder. while vigorously stirring it was stirred at this temperature for 24 h The organic layer was separated the aqueous layer was extracted with 3×50 ml of dichloromethane The combined organic layers were dried over Na2SO4 evaporated to dryness The residue was dissolved in 250 ml of toluene 0.75 g of p-TosOH was added The resulting solution was refluxed for 1 hours to remove the water formed Next, the mixture was evaporated to dryness the product was isolated by flash-chromatography on Silica Gel 60 (d 50 mm, l 400 mm, eluent: hexanes)

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

Procedure: To a solution of 12.6 g (40.0 mmol) of 1,3,5-tribromobenzene in 400 ml of ether, 160 ml (40.0 mmol) of 0.25 M nBuLi in hexanes was added for 1 h at −80° C. The mixture was stirred for 1.5 h at this temperature, and then a solution of 5.29 g (40.0 mmol) of indanone-2 in 200 ml of ether was added dropwise over 1 hour while vigorously stirring. The reaction mixture was allowed to warm to room temperature and it was stirred at this temperature for 24 h. Then, 100 ml of water was added. The organic layer was separated; the aqueous layer was extracted with 3×50 ml of dichloromethane. The combined organic layers were dried over Na2SO4 and then evaporated to dryness. The residue was dissolved in 250 ml of toluene, and 0.75 g of p-TosOH was added. The resulting solution was refluxed for 1 hours using a Dean-Stark trap to remove the water formed. Next, the mixture was evaporated to dryness, and the product was isolated by flash-chromatography on Silica Gel 60 (d 50 mm, l 400 mm, eluent: hexanes). Yield 8.54 g (61%) of white powder. while vigorously stirring it was stirred at this temperature for 24 h The organic layer was separated the aqueous layer was extracted with 3×50 ml of dichloromethane The combined organic layers were dried over Na2SO4 evaporated to dryness The residue was dissolved in 250 ml of toluene 0.75 g of p-TosOH was added The resulting solution was refluxed for 1 hours to remove the water formed Next, the mixture was evaporated to dryness the product was isolated by flash-chromatography on Silica Gel 60 (d 50 mm, l 400 mm, eluent: hexanes)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6.25 ml (0.01 mol) of 1.6 M butyllithium in hexane are added over 5 minutes at -78° C. to a suspension of 3.14 g (0.01 mol) of 1,3,5-tribromobenzene in 50 ml of diethyl ether. The reaction mixture is stirred at -78° C. for 2 hours, during which a yellow-orange suspension is produced. 2.68 g (0.01 mol) of solid dimesitylfluoroborane are added, and the reaction mixture is warmed to room temperature over about one hour. The mixture is then diluted with 50 ml of hexane and cooled to 0° C. The solid produced is filtered, washed several times with cold hexane and then washed with water and, finally, with methanol, until the solid is colourless. Drying gives 3.54 g (0.0073 mol; i.e. 73% of theory) of a white solid (1,3-dibromo-5-dimesitylborylbenzene). Following purification by chromatography (hexane; SiO2) a melting point of 190-191° C. is obtained. Elemental analysis for C24H25BBr2 gives: C calc.: 59.55%; found: 59.52% H calc.: 5.21%; found: 5,12% is produced the reaction mixture is warmed to room temperature over about one hour cooled to 0° C The solid produced is filtered washed several times with cold hexane washed with water Drying