1-bromo-2-methylsulfanylbenzene

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

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

Procedure: (2-bromophenyl)(methyl)sulfane (25 g, 123 mmol), Pd2dba3 (6.75 g, 7.38 mmol), S-Phos (6.06 g,14.77 mmol) and sodium tert-butoxide (17.74 g, 185 mmol) were placed in a dry 3 neck flask under N2. The reaction mixture was vacuum evacuated and back filled with N2 three times. Aniline (22.93 g, 246 mmol) and 500 mL toluene were added to the reaction mixture. The reaction mixture was refluxed for 18 hours. The crude reaction mixture was run through a silica gel plug and eluted with toluene. The toluene portion was concentrated down and subjected to a silica gel column by using 3-5% DCM in hexanes to yield desired product. (24 g, 111 mmol, 91%) a dry 3 neck flask under N2 evacuated back filled with N2 three times The reaction mixture was refluxed for 18 hours The crude reaction mixture eluted with toluene The toluene portion was concentrated down

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

Procedure: A solution of 1-methylthio-2-bromobenzene (5 g) in dry ether (30 ml) was stirred at 0° C. and 1.63M n-butyllithium in hexane solution (16.6 ml) was added dropwise over a period of 15 minutes. The reaction mixture was stirred at 0° C. for 1.5 hours and then transferred to a cold (-78° C.) solution of triisopropyl borate (7.4 ml) in tetrahydrofuran (40 ml) over 40 minutes. After stirring for 1 hour at -78° C., the reaction mixture was allowed to warm to room temperature overnight. The suspension was poured into dilute 2M hydrochloric acid (40 ml) and the layers were separated. The aqueous phase was extracted with ether (2×80 ml) and the combined organic phases were washed with brine, dried with magnesium sulfate, evaporated and washed with petroleum ether (2×20 ml) to afford 2-methylthiophenyldihydroxyborane. After stirring for 1 hour at -78° C. to warm to room temperature overnight The suspension was poured the layers were separated The aqueous phase was extracted with ether (2×80 ml) the combined organic phases were washed with brine dried with magnesium sulfate evaporated washed with petroleum ether (2×20 ml)

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

Procedure: 2-Bromothioanisole (29.0 g, 143 mmol) was dissolved in dry THF (400 mL) and cooled to −75° C. n-BuLi (62.0 mL, 2.5 M in hexane, 155 mmol) was added over 50 minutes. After stirring 25 minutes, triisopropyl borate (46 mL, 199 mmol) was added over 35 minutes. The cold bath was removed and the reaction was stirred at room temp for 16 hours. The resulting solution was cooled in an ice bathours, and 6 M HCl (100 mL) was added. This mixture was stirred at room temp 5 hours and concentrated to about half of the original volume. The concentrated solution was partitioned between Et2O and water. The organic layer was extracted with 2 M NaOH, which was subsequently reacidified with 6 M HCl and extracted several times back into Et2O. These Et2O washes were dried over Na2SO4, filtered, and evaporated to yield a beige solid (20.4 g, 85%). 1H NMR (CDCl3): δ 8.01 (dd, 1H, J=7.3, J′=1.4), 7.53 (dd, 1H, J=7.7, J′=1.1), 7.43 (td, 1H, J=7.3, J′=1.8), 7.34 (td, 1H, J=7.3, J′=1.5), 6.22 (s, 2H), 2.50 (s, 3H). was added over 50 minutes The cold bath was removed the reaction was stirred at room temp for 16 hours The resulting solution was cooled in an ice bathours, and 6 M HCl (100 mL) was added This mixture was stirred at room temp 5 hours concentrated to about half of the original volume The concentrated solution was partitioned between Et2O and water The organic layer was extracted with 2 M NaOH, which extracted several times back into Et2O These Et2O washes were dried over Na2SO4 filtered evaporated

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

Procedure: To a mixture of 2-bromothioanisole (4.8 g, 23.6 mmol), 4-carboxybenzeneboronic acid (3.92 g, 23.6 mmol) and 2M K2CO3 (35.5 mmol, 71 mmol) in dioxane (20 ml) was added dichlorobis(triphenylphosphine)palladium (II) (415 mg, 0.6 mmol) under Ar. It was refluxed for 2 hrs. After the removal of the solvent, the residue was neutralized by 1 N HCl and extracted with dichloromethane. The organic layer was dried over MgSO4 and concentrated in vacuo to give 4-[(2-ethylthio)phenyl]benzoic acid (5.9 g, 100%). ES-MS (M+H)+=245. It was refluxed for 2 hrs After the removal of the solvent extracted with dichloromethane The organic layer was dried over MgSO4 concentrated in vacuo

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

Procedure: Magnesium (9.52 g) was suspended in 119 mL of tetrahydrofuran, and to the suspension were added 3.00 g of 2-bromothioanisole and about 20 mg of iodine. After the reaction was started by heating employing a dryer, 72 g of 2-bromo-thioanisole was dropped to the mixture during 20 minutes. After being heated for 1 hour, the reaction mixture was diluted with 1000 mL of tetrahydrofuran, and cooled to 0° C. To the mixture was added 102 mL of triisopropyl borate at the same temperature, and the mixture was stirred at room temperature for 4 hours. To the reaction mixture was added water, and the solvent was removed under reduced pressure. The residue was added 500 mL of 2 mol/L hydrochloric acid, and the mixture was extracted with 300 mL of diethyl ether. The organic layer was extracted with 500 mL of 2 mol/L aqueous sodium hydroxide solution, and the aqueous layer was acidified by addition of concentrated hydrochloric acid under ice-cooling. The residual diethyl ether was removed under reduced pressure, and the precipitate was collected by filtration to give 45.95 g of 2-(methylthio)-phenylboronic acid. by heating was dropped to the mixture during 20 minutes After being heated for 1 hour the solvent was removed under reduced pressure The residue was added 500 mL of 2 mol/L hydrochloric acid the mixture was extracted with 300 mL of diethyl ether The organic layer was extracted with 500 mL of 2 mol/L aqueous sodium hydroxide solution the aqueous layer was acidified by addition of concentrated hydrochloric acid under ice- cooling The residual diethyl ether was removed under reduced pressure the precipitate was collected by filtration

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

Procedure: Magnesium (9.52 g) was suspended in 119 mL of tetrahydrofuran, and to the suspension were added 3.00 g of 2-bromothioanisole and about 20 mg of iodine. After the reaction was started by heating employing a dryer, 72 g of 2-bromo-thioanisole was dropped to the mixture during 20 minutes. After being heated for 1 hour, the reaction mixture was diluted with 1000 mL of tetrahydrofuran, and cooled to 0° C. To the mixture was added 102 mL of triisopropyl borate at the same temperature, and the mixture was stirred at room temperature for 4 hours. To the reaction mixture was added water, and the solvent was removed under reduced pressure. The residue was added 500 mL of 2 mol/L hydrochloric acid, and the mixture was extracted with 300 mL of diethyl ether. The organic layer was extracted with 500 mL of 2 mol/L aqueous sodium hydroxide solution, and the aqueous layer was acidified by addition of concentrated hydrochloric acid under ice-cooling. The residual diethyl ether was removed under reduced pressure, and the precipitate was collected by filtration to give 45.95 g of 2-(methylthio)-phenylboronic acid. by heating was dropped to the mixture during 20 minutes After being heated for 1 hour the solvent was removed under reduced pressure The residue was added 500 mL of 2 mol/L hydrochloric acid the mixture was extracted with 300 mL of diethyl ether The organic layer was extracted with 500 mL of 2 mol/L aqueous sodium hydroxide solution the aqueous layer was acidified by addition of concentrated hydrochloric acid under ice- cooling The residual diethyl ether was removed under reduced pressure the precipitate was collected by filtration

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

Procedure: 2-Bromothioanisole (29.0 g, 143 mmol) was dissolved in dry THF (400 mL) and cooled to -75° C. n-BuLi (62.0 mL, 2.5 M in hexane, 155 mmol) was added over 50 minutes. After stirring 25 minutes, triisopropyl borate (46 mL, 199 mmol) was added over 35 minutes. The cold bath was removed and the reaction was stirred at room temp for 16 hours. The resulting solution was cooled in an ice bathours, and 6 M HCl (100 mL) was added. This mixture was stirred at room temp 5 hours and concentrated to about half of the original volume. The concentrated solution was partitioned between Et2O and water. The organic layer was extracted with 2 M NaOH, which was subsequently reacidified with 6 M HCl and extracted several times back into Et2O. These Et2O washes were dried over Na2SO4, filtered, and evaporated to yield a beige solid (20.4 g, 85%). 1H NMR (CDCl3): δ8.01 (dd, 1H, J=7.3, J'=1.4), 7.53 (dd, 1H, J=7.7, J'=1.1), 7.43 (td, 1H, J=7.3, J'=1.8), 7.34 (td, 1H, J=7.3, J'=1.5), 6.22 (s, 2H) , 2.50 (s, 3H). was added over 50 minutes The cold bath was removed the reaction was stirred at room temp for 16 hours The resulting solution was cooled in an ice bathours, and 6 M HCl (100 mL) was added This mixture was stirred at room temp 5 hours concentrated to about half of the original volume The concentrated solution was partitioned between Et2O and water The organic layer was extracted with 2 M NaOH, which extracted several times back into Et2O These Et2O washes were dried over Na2SO4 filtered evaporated

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

Procedure: 2-Bromothioanisole (29.0 g, 143 mmol) was dissolved in dry THF (400 mL) and cooled to -75° C. n-BuLi (62.0 mL, 2.5 M in hexane, 155 mmol) was added over 50 minutes. After stirring 25 minutes, triisopropyl borate (46 mL, 199 mmol) was added over 35 minutes. The cold bath was removed and the reaction was stirred at room temp for 16 hours. The resulting solution was cooled in an ice bathours, and 6 M HCl (100 mL) was added. This mixture was stirred at room temp 5 hours and concentrated to about half of the original volume. The concentrated solution was partitioned between Et2O and water. The organic layer was extracted with 2 M NaOH, which was subsequently reacidified with 6 M HCl and extracted several times back into Et2O. These Et2O washes were dried over Na2SO4, filtered, and evaporated to yield a beige solid (20.4 g, 85%). 1H NMR (CDCl3): δ8.01 (dd, 1H, J=7.3, J'=1.4), 7.53 (dd, 1H, J=7.7, J'=1.1), 7.43 (td, 1H, J=7.3, J'=1.8), 7.34 (td, 1H, J=7.3, J'=1.5), 6.22 (s, 2H) , 2.50 (s, 3H). was added over 50 minutes The cold bath was removed the reaction was stirred at room temp for 16 hours The resulting solution was cooled in an ice bathours, and 6 M HCl (100 mL) was added This mixture was stirred at room temp 5 hours concentrated to about half of the original volume The concentrated solution was partitioned between Et2O and water The organic layer was extracted with 2 M NaOH, which extracted several times back into Et2O These Et2O washes were dried over Na2SO4 filtered evaporated

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

Procedure: 2.9 g (118 mmol) of magnesium turnings was introduced into 100 ml of tetrahydrofuran (dried over molecular sieve) under argon. Approximately 5 g of 2-bromothioanisole was added dropwise at room temperature, and the mixture was heated to 50° C. After the Grignard reaction had started, the mixture warmed further to reflux. The remainder of the total of 20.0 g (98.5 mmol) of 2-bromothioanisole was added dropwise so that the reaction mixture continued to reflux. The resultant solution of the Grignard compound 2-(methylthio)phenylmagnesium bromide was then allowed to cool slowly to room temperature. Working under argon, 250 ml of dried tetrahydrofuran was introduced into a second flask; 11.7 g (148 mmol) of pyridine and 0.93 g (4.9 mmol) of copper(I) iodide were added; and the mixture was cooled to -30° C. At -30° to -25° C., 16.8 g (98.5 mmol) of benzyl chloroformate was added dropwise, a yellow-red precipitate being formed first, followed by a beige suspension. The solution of the Grignard compound was added dropwise to this suspension at the same temperature; cooling was then stopped and the mixture was stirred for a further 2 hours after it had reached room temperature. The reaction mixture was poured into 120 ml of 20 percent strength aqueous ammonium chloride solution and stirred vigorously. 500 ml of toluene was then added and the phases were separated. The deep blue aqueous phase was extracted three times with 50 ml of toluene each time, and the combined organic phases were dried over sodium sulfate and evaporated to dryness using a rotary evaporator. The brown residue was kept under high vacuum for a further 1 hour to remove solvent residues, then dissolved in 500 to 1000 ml of boiling methanol and filtered while still hot. The filtrate was cooled slowly to room temperature and eventually to +2° C., the product forming as a voluminous yellowish-white precipitate. This was filtered off and dried at 35° C. in vacuo. The yield of the product was 20.8 g (62.7 percent) of yellowish-white solids. Other data concerning the product was: After the Grignard reaction the mixture warmed further to reflux to reflux to cool slowly to room temperature and the mixture was cooled to -30° C a yellow-red precipitate being formed first The solution of the Grignard compound was added dropwise to this suspension at the same temperature cooling had reached room temperature stirred vigorously the phases were separated The deep blue aqueous phase was extracted three times with 50 ml of toluene each time the combined organic phases were dried over sodium sulfate evaporated to dryness a rotary evaporator The brown residue was kept under high vacuum for a further 1 hour to remove solvent residues dissolved in 500 to 1000 ml of boiling methanol filtered while still hot The filtrate was cooled slowly to room temperature and eventually to +2° C. the product forming as a voluminous yellowish-white precipitate This was filtered off dried at 35° C. in vacuo

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

Procedure: 2.9 g (118 mmol) of magnesium turnings was introduced into 100 ml of tetrahydrofuran (dried over molecular sieve) under argon. Approximately 5 g of 2-bromothioanisole was added dropwise at room temperature, and the mixture was heated to 50° C. After the Grignard reaction had started, the mixture warmed further to reflux. The remainder of the total of 20.0 g (98.5 mmol) of 2-bromothioanisole was added dropwise so that the reaction mixture continued to reflux. The resultant solution of the Grignard compound 2-(methylthio)phenylmagnesium bromide was then allowed to cool slowly to room temperature. Working under argon, 250 ml of dried tetrahydrofuran was introduced into a second flask; 11.7 g (148 mmol) of pyridine and 0.93 g (4.9 mmol) of copper(I) iodide were added; and the mixture was cooled to -30° C. At -30° to -25° C., 16.8 g (98.5 mmol) of benzyl chloroformate was added dropwise, a yellow-red precipitate being formed first, followed by a beige suspension. The solution of the Grignard compound was added dropwise to this suspension at the same temperature; cooling was then stopped and the mixture was stirred for a further 2 hours after it had reached room temperature. The reaction mixture was poured into 120 ml of 20 percent strength aqueous ammonium chloride solution and stirred vigorously. 500 ml of toluene was then added and the phases were separated. The deep blue aqueous phase was extracted three times with 50 ml of toluene each time, and the combined organic phases were dried over sodium sulfate and evaporated to dryness using a rotary evaporator. The brown residue was kept under high vacuum for a further 1 hour to remove solvent residues, then dissolved in 500 to 1000 ml of boiling methanol and filtered while still hot. The filtrate was cooled slowly to room temperature and eventually to +2° C., the product forming as a voluminous yellowish-white precipitate. This was filtered off and dried at 35° C. in vacuo. The yield of the product was 20.8 g (62.7 percent) of yellowish-white solids. Other data concerning the product was: After the Grignard reaction the mixture warmed further to reflux to reflux to cool slowly to room temperature and the mixture was cooled to -30° C a yellow-red precipitate being formed first The solution of the Grignard compound was added dropwise to this suspension at the same temperature cooling had reached room temperature stirred vigorously the phases were separated The deep blue aqueous phase was extracted three times with 50 ml of toluene each time the combined organic phases were dried over sodium sulfate evaporated to dryness a rotary evaporator The brown residue was kept under high vacuum for a further 1 hour to remove solvent residues dissolved in 500 to 1000 ml of boiling methanol filtered while still hot The filtrate was cooled slowly to room temperature and eventually to +2° C. the product forming as a voluminous yellowish-white precipitate This was filtered off dried at 35° C. in vacuo

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

Procedure: (2-bromophenyl)(methyl)sulfane (25 g, 123 mmol), Pd2dba3 (6.75 g, 7.38 mmol), S-Phos (6.06 g,14.77 mmol) and sodium tert-butoxide (17.74 g, 185 mmol) were placed in a dry 3 neck flask under N2. The reaction mixture was vacuum evacuated and back filled with N2 three times. Aniline (22.93 g, 246 mmol) and 500 mL toluene were added to the reaction mixture. The reaction mixture was refluxed for 18 hours. The crude reaction mixture was run through a silica gel plug and eluted with toluene. The toluene portion was concentrated down and subjected to a silica gel column by using 3-5% DCM in hexanes to yield desired product. (24 g, 111 mmol, 91%) a dry 3 neck flask under N2 evacuated back filled with N2 three times The reaction mixture was refluxed for 18 hours The crude reaction mixture eluted with toluene The toluene portion was concentrated down