1-Bromobenzocyclobutene

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

Procedure: To a stirred solution of mercury(II) oxide (591.3 mg, 2.73 mmol) and 35% aqueous tetrafluoroboric acid (TFBA) (999.4 mg, 5.46 mmol) in 1,4-dioxane (10.9 mL), 1-bromobenzocyclobutene (1.0 g, 5.46 mmol) was added. The reaction stirred at room temperature for 2 h and was then treated successively with NaHCO3 and 3N KOH until the solution remained basic. The precipitated mercury(II) oxide was filtered off and the filtrate extracted with CH2Cl2 (3×300 mL), dried with anhydrous Na2SO4, filtered, and concentrated to yield white crystals that were purified via column chromatography using a 3:2 Hexanes:EtOAc solvent system. The precipitated mercury(II) oxide was filtered off the filtrate extracted with CH2Cl2 (3×300 mL) dried with anhydrous Na2SO4 filtered concentrated to yield white crystals that were purified via column chromatography

Conditions: temp:145.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 250 mL round bottomed flask equipped with a drying tube and a condenser, a solution of cycloheptatriene (30.7 g, 300 mmol), bromoform (25.3 g, 100 mmol), anhydrous K2CO3 (15.0 g, 109 mmol), and 18-crown-6 (0.75 g) was heated with stirring at 145° C. for 9-10 h. The solution was allowed to cool and diluted with an equal volume of acetone. Silica gel (15.0 g) was added to reaction mixture and the insoluble solid residue was separated via vacuum filtration and the filter cake washed with acetone until the washings were colorless. The filtrate was concentrated and distilled to remove residual cycloheptatriene. The viscous, brown residue was precipitated into hot petroleum ether. After filtration to remove the precipitate, the filtrate was concentrated and distilled in vacuo through a Vigreaux column to give slightly impure product. Pure 1-bromobenzocyclobutene was obtained as a light yellow liquid by redistillation yield (2.95 g, 5.94%). 1H NMR (300 MHz, CDCl3) δ 7.28 (m, 1H, ArH), 7.16 (d, 1H, J=7.0 Hz, ArH), 7.07 (d, 1H, J=6.4 Hz, ArH), 5.39 (m, 1H, CH), 3.85 (dd, 1H, J=4.4 Hz, J=14.7 Hz, CH2), 3.45 (d, 1H, J=14.7 Hz, CH2). In a 250 mL round bottomed flask equipped with a drying tube and a condenser to cool Silica gel (15.0 g) was added to reaction mixture the insoluble solid residue was separated via vacuum filtration the filter cake washed with acetone until the washings The filtrate was concentrated distilled to remove residual cycloheptatriene The viscous, brown residue was precipitated into hot petroleum ether After filtration to remove the precipitate the filtrate was concentrated distilled in vacuo through a Vigreaux column to give slightly impure product

Conditions: temp:145.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 250 mL round bottomed flask equipped with a drying tube and a condenser, a solution of cycloheptatriene (30.7 g, 300 mmol), bromoform (25.3 g, 100 mmol), anhydrous K2CO3 (15.0 g, 109 mmol), and 18-crown-6 (0.75 g) was heated with stirring at 145° C. for 9-10 h. The solution was allowed to cool and diluted with an equal volume of acetone. Silica gel (15.0 g) was added to reaction mixture and the insoluble solid residue was separated via vacuum filtration and the filter cake washed with acetone until the washings were colorless. The filtrate was concentrated and distilled to remove residual cycloheptatriene. The viscous, brown residue was precipitated into hot petroleum ether. After filtration to remove the precipitate, the filtrate was concentrated and distilled in vacuo through a Vigreaux column to give slightly impure product. Pure 1-bromobenzocyclobutene was obtained as a light yellow liquid by redistillation yield (2.95 g, 5.94%). 1H NMR (300 MHz, CDCl3) δ 7.28 (m, 1H, ArH), 7.16 (d, 1H, J=7.0 Hz, ArH), 7.07 (d, 1H, J=6.4 Hz, ArH), 5.39 (m, 1H, CH), 3.85 (dd, 1H, J=4.4 Hz, J=14.7 Hz, CH2), 3.45 (d, 1H, J=14.7 Hz, CH2). In a 250 mL round bottomed flask equipped with a drying tube and a condenser to cool Silica gel (15.0 g) was added to reaction mixture the insoluble solid residue was separated via vacuum filtration the filter cake washed with acetone until the washings The filtrate was concentrated distilled to remove residual cycloheptatriene The viscous, brown residue was precipitated into hot petroleum ether After filtration to remove the precipitate the filtrate was concentrated distilled in vacuo through a Vigreaux column to give slightly impure product

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

Procedure: To a stirred solution of mercury(II) oxide (591.3 mg, 2.73 mmol) and 35% aqueous tetrafluoroboric acid (TFBA) (999.4 mg, 5.46 mmol) in 1,4-dioxane (10.9 mL), 1-bromobenzocyclobutene (1.0 g, 5.46 mmol) was added. The reaction stirred at room temperature for 2 h and was then treated successively with NaHCO3 and 3N KOH until the solution remained basic. The precipitated mercury(II) oxide was filtered off and the filtrate extracted with CH2Cl2 (3×300 mL), dried with anhydrous Na2SO4, filtered, and concentrated to yield white crystals that were purified via column chromatography using a 3:2 Hexanes:EtOAc solvent system. The precipitated mercury(II) oxide was filtered off the filtrate extracted with CH2Cl2 (3×300 mL) dried with anhydrous Na2SO4 filtered concentrated to yield white crystals that were purified via column chromatography

Conditions: temp:145.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 250 mL round bottomed flask equipped with a drying tube and a condenser, a solution of cycloheptatriene (30.7 g, 300 mmol), bromoform (25.3 g, 100 mmol), anhydrous K2CO3 (15.0 g, 109 mmol), and 18-crown-6 (0.75 g) was heated with stirring at 145° C. for 9-10 h. The solution was allowed to cool and diluted with an equal volume of acetone. Silica gel (15.0 g) was added to reaction mixture and the insoluble solid residue was separated via vacuum filtration and the filter cake washed with acetone until the washings were colorless. The filtrate was concentrated and distilled to remove residual cycloheptatriene. The viscous, brown residue was precipitated into hot petroleum ether. After filtration to remove the precipitate, the filtrate was concentrated and distilled in vacuo through a Vigreaux column to give slightly impure product. Pure 1-bromobenzocyclobutene was obtained as a light yellow liquid by redistillation yield (2.95 g, 5.94%). 1H NMR (300 MHz, CDCl3) δ 7.28 (m, 1H, ArH), 7.16 (d, 1H, J=7.0 Hz, ArH), 7.07 (d, 1H, J=6.4 Hz, ArH), 5.39 (m, 1H, CH), 3.85 (dd, 1H, J=4.4 Hz, J=14.7 Hz, CH2), 3.45 (d, 1H, J=14.7 Hz, CH2). In a 250 mL round bottomed flask equipped with a drying tube and a condenser to cool Silica gel (15.0 g) was added to reaction mixture the insoluble solid residue was separated via vacuum filtration the filter cake washed with acetone until the washings The filtrate was concentrated distilled to remove residual cycloheptatriene The viscous, brown residue was precipitated into hot petroleum ether After filtration to remove the precipitate the filtrate was concentrated distilled in vacuo through a Vigreaux column to give slightly impure product

Conditions: temp:145.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 250 mL round bottomed flask equipped with a drying tube and a condenser, a solution of cycloheptatriene (30.7 g, 300 mmol), bromoform (25.3 g, 100 mmol), anhydrous K2CO3 (15.0 g, 109 mmol), and 18-crown-6 (0.75 g) was heated with stirring at 145° C. for 9-10 h. The solution was allowed to cool and diluted with an equal volume of acetone. Silica gel (15.0 g) was added to reaction mixture and the insoluble solid residue was separated via vacuum filtration and the filter cake washed with acetone until the washings were colorless. The filtrate was concentrated and distilled to remove residual cycloheptatriene. The viscous, brown residue was precipitated into hot petroleum ether. After filtration to remove the precipitate, the filtrate was concentrated and distilled in vacuo through a Vigreaux column to give slightly impure product. Pure 1-bromobenzocyclobutene was obtained as a light yellow liquid by redistillation yield (2.95 g, 5.94%). 1H NMR (300 MHz, CDCl3) δ 7.28 (m, 1H, ArH), 7.16 (d, 1H, J=7.0 Hz, ArH), 7.07 (d, 1H, J=6.4 Hz, ArH), 5.39 (m, 1H, CH), 3.85 (dd, 1H, J=4.4 Hz, J=14.7 Hz, CH2), 3.45 (d, 1H, J=14.7 Hz, CH2). In a 250 mL round bottomed flask equipped with a drying tube and a condenser to cool Silica gel (15.0 g) was added to reaction mixture the insoluble solid residue was separated via vacuum filtration the filter cake washed with acetone until the washings The filtrate was concentrated distilled to remove residual cycloheptatriene The viscous, brown residue was precipitated into hot petroleum ether After filtration to remove the precipitate the filtrate was concentrated distilled in vacuo through a Vigreaux column to give slightly impure product

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

Procedure: To a stirred solution of mercury(II) oxide (591.3 mg, 2.73 mmol) and 35% aqueous tetrafluoroboric acid (TFBA) (999.4 mg, 5.46 mmol) in 1,4-dioxane (10.9 mL), 1-bromobenzocyclobutene (1.0 g, 5.46 mmol) was added. The reaction stirred at room temperature for 2 h and was then treated successively with NaHCO3 and 3N KOH until the solution remained basic. The precipitated mercury(II) oxide was filtered off and the filtrate extracted with CH2Cl2 (3×300 mL), dried with anhydrous Na2SO4, filtered, and concentrated to yield white crystals that were purified via column chromatography using a 3:2 Hexanes:EtOAc solvent system. The precipitated mercury(II) oxide was filtered off the filtrate extracted with CH2Cl2 (3×300 mL) dried with anhydrous Na2SO4 filtered concentrated to yield white crystals that were purified via column chromatography

Conditions: temp:145.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 250 mL round bottomed flask equipped with a drying tube and a condenser, a solution of cycloheptatriene (30.7 g, 300 mmol), bromoform (25.3 g, 100 mmol), anhydrous K2CO3 (15.0 g, 109 mmol), and 18-crown-6 (0.75 g) was heated with stirring at 145° C. for 9-10 h. The solution was allowed to cool and diluted with an equal volume of acetone. Silica gel (15.0 g) was added to reaction mixture and the insoluble solid residue was separated via vacuum filtration and the filter cake washed with acetone until the washings were colorless. The filtrate was concentrated and distilled to remove residual cycloheptatriene. The viscous, brown residue was precipitated into hot petroleum ether. After filtration to remove the precipitate, the filtrate was concentrated and distilled in vacuo through a Vigreaux column to give slightly impure product. Pure 1-bromobenzocyclobutene was obtained as a light yellow liquid by redistillation yield (2.95 g, 5.94%). 1H NMR (300 MHz, CDCl3) δ 7.28 (m, 1H, ArH), 7.16 (d, 1H, J=7.0 Hz, ArH), 7.07 (d, 1H, J=6.4 Hz, ArH), 5.39 (m, 1H, CH), 3.85 (dd, 1H, J=4.4 Hz, J=14.7 Hz, CH2), 3.45 (d, 1H, J=14.7 Hz, CH2). In a 250 mL round bottomed flask equipped with a drying tube and a condenser to cool Silica gel (15.0 g) was added to reaction mixture the insoluble solid residue was separated via vacuum filtration the filter cake washed with acetone until the washings The filtrate was concentrated distilled to remove residual cycloheptatriene The viscous, brown residue was precipitated into hot petroleum ether After filtration to remove the precipitate the filtrate was concentrated distilled in vacuo through a Vigreaux column to give slightly impure product

Conditions: temp:145.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 250 mL round bottomed flask equipped with a drying tube and a condenser, a solution of cycloheptatriene (30.7 g, 300 mmol), bromoform (25.3 g, 100 mmol), anhydrous K2CO3 (15.0 g, 109 mmol), and 18-crown-6 (0.75 g) was heated with stirring at 145° C. for 9-10 h. The solution was allowed to cool and diluted with an equal volume of acetone. Silica gel (15.0 g) was added to reaction mixture and the insoluble solid residue was separated via vacuum filtration and the filter cake washed with acetone until the washings were colorless. The filtrate was concentrated and distilled to remove residual cycloheptatriene. The viscous, brown residue was precipitated into hot petroleum ether. After filtration to remove the precipitate, the filtrate was concentrated and distilled in vacuo through a Vigreaux column to give slightly impure product. Pure 1-bromobenzocyclobutene was obtained as a light yellow liquid by redistillation yield (2.95 g, 5.94%). 1H NMR (300 MHz, CDCl3) δ 7.28 (m, 1H, ArH), 7.16 (d, 1H, J=7.0 Hz, ArH), 7.07 (d, 1H, J=6.4 Hz, ArH), 5.39 (m, 1H, CH), 3.85 (dd, 1H, J=4.4 Hz, J=14.7 Hz, CH2), 3.45 (d, 1H, J=14.7 Hz, CH2). In a 250 mL round bottomed flask equipped with a drying tube and a condenser to cool Silica gel (15.0 g) was added to reaction mixture the insoluble solid residue was separated via vacuum filtration the filter cake washed with acetone until the washings The filtrate was concentrated distilled to remove residual cycloheptatriene The viscous, brown residue was precipitated into hot petroleum ether After filtration to remove the precipitate the filtrate was concentrated distilled in vacuo through a Vigreaux column to give slightly impure product

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

Procedure: Bromobenzocyclobutene (91.5 g, 0.5 mol) and chlorobenzene(anhydrous, 2500 mL) were charged into a four-neck 5 L flask equipped with mechanical stir, condenser, N2 (in and outlet) and thermometer. The reaction mixture was heated to 120° C., and N-bromosuccinimide (111.3 g, 0.625 mol) was gradually charged over 30 min., followed by slowly feeding a mixture of a free radical azo compound source (VAZO™ 68) (14.0 g, 0.05 mol) and chlorobenzene (500 mL) over 30 min. Then the reaction mixture was heated to 133° C. (mild reflux) and kept at that temperature for 6 hr. The mixture was then cooled to room temperature overnight, and chlorobenzene was removed by vacuum evaporation. The crude product was extracted with hexane. After removal of hexane, 1-bromo-bromobenzocyclobutene (1-Br-BrBCB) (80-85° C/0.35 torr, 90 g, ca. 93% purity) was obtained by vacuum distillation. Then the reaction mixture was heated to 133° C. (mild reflux) The mixture was then cooled to room temperature overnight chlorobenzene was removed by vacuum evaporation The crude product was extracted with hexane After removal of hexane

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

Procedure: Bromobenzocyclobutene (91.5 g, 0.5 mol) and chlorobenzene(anhydrous, 2500 mL) were charged into a four-neck 5 L flask equipped with mechanical stir, condenser, N2 (in and outlet) and thermometer. The reaction mixture was heated to 120° C., and N-bromosuccinimide (111.3 g, 0.625 mol) was gradually charged over 30 min., followed by slowly feeding a mixture of a free radical azo compound source (VAZO™ 68) (14.0 g, 0.05 mol) and chlorobenzene (500 mL) over 30 min. Then the reaction mixture was heated to 133° C. (mild reflux) and kept at that temperature for 6 hr. The mixture was then cooled to room temperature overnight, and chlorobenzene was removed by vacuum evaporation. The crude product was extracted with hexane. After removal of hexane, 1-bromo-bromobenzocyclobutene (1-Br-BrBCB) (80-85° C/0.35 torr, 90 g, ca. 93% purity) was obtained by vacuum distillation. Then the reaction mixture was heated to 133° C. (mild reflux) The mixture was then cooled to room temperature overnight chlorobenzene was removed by vacuum evaporation The crude product was extracted with hexane After removal of hexane

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

Procedure: Sodium (464 mg, 20.2 mmol, 1.2 eq.) was allowed to react with absolute ethanol (40 mL, 0.42 M); to the resulting mixture was added ethyl 2-(acetylamino)-2-cyanoacetate (3.44 g, 20.2 mmol, 1.2 eq.). After 20 minutes at 60° C., 7-bromobicyclo[4.2.0]octa-1,3,5-triene (3.092 g, 16.89 mmol, 1 eq.) was added and the reaction mixture was heated at reflux overnight, then filtered and concentrated in vacuo. The residue was diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo to give a dark oil, which was purified by silica gel chromatography (Gradient: 0% to 50% ethyl acetate in heptane) to give #99 (4.38 g) as a yellow gum. LC-MS: m/z 273.2 [M+H+], retention time=2.36 minutes. the reaction mixture was heated at reflux overnight filtered concentrated in vacuo The residue was diluted with water extracted with ethyl acetate The organic layer was washed with brine dried over sodium sulfate filtered concentrated in vacuo to give a dark oil, which was purified by silica gel chromatography (Gradient: 0% to 50% ethyl acetate in heptane)