2-(4-iodophenyl)ethynyl-trimethylsilane

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

Procedure: To a solution of ((4-iodophenyl)ethynyl)trimethylsilane (5) (2.07 g, 6.23 mmol) in methanol (40 mL) was added K2CO3 (8.0 g, 57.9 mmol) and the reaction was allowed to stir for 48 hours. The volatiles were then removed in vacuo and the residue partitioned between ethyl acetate and H2O. The layers were separated and the aqueous phase re-extracted with ethyl acetate (2×). The combined organic layers were washed (H2O, brine), dried (Na2SO4), and filtered. The solvent was removed in vacuo and the residue was crystallized from hexane at −20° C. (in 2 crops) to give 1-ethynyl-4-iodobenzene (6) as a colorless solid (0.92 g, 64%). 1H NMR (400 MHz, DMSO-d6) δ 7.66 (app d, J=8.6 Hz, 2H), 7.20 (app d, J=8.5 Hz, 2H), 1.54 (s, 1H). The volatiles were then removed in vacuo the residue partitioned between ethyl acetate and H2O The layers were separated the aqueous phase re-extracted with ethyl acetate (2×) The combined organic layers were washed (H2O, brine) dried (Na2SO4) filtered The solvent was removed in vacuo the residue was crystallized from hexane at −20° C. (in 2 crops)

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

Procedure: To a solution of ((4-iodophenyl)ethynyl)trimethylsilane (5) (2.07 g, 6.23 mmol) in methanol (40 mL) was added K2CO3 (8.0 g, 57.9 mmol) and the reaction was allowed to stir for 48 hours. The volatiles were then removed in vacuo and the residue partitioned between ethyl acetate and H2O. The layers were separated and the aqueous phase re-extracted with ethyl acetate (2×). The combined organic layers were washed (H2O, brine), dried (Na2SO4), and filtered. The solvent was removed in vacuo and the residue was crystallized from hexane at −20° C. (in 2 crops) to give 1-ethynyl-4-iodobenzene (6) as a colorless solid (0.92 g, 64%). 1H NMR (400 MHz, DMSO-d6) δ 7.66 (app d, J=8.6 Hz, 2H), 7.20 (app d, J=8.5 Hz, 2H), 1.54 (s, 1H). The volatiles were then removed in vacuo the residue partitioned between ethyl acetate and H2O The layers were separated the aqueous phase re-extracted with ethyl acetate (2×) The combined organic layers were washed (H2O, brine) dried (Na2SO4) filtered The solvent was removed in vacuo the residue was crystallized from hexane at −20° C. (in 2 crops)

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

Procedure: Into a 100 ml round bottom flask was placed a mixture of 1.31 g (0.0081 mole) of 3.5-dimethoxyphenylacetylene, 2.25 g (0.0075 mole) of 4-iodophenyl-trimethylsilylacetylene, 0.016 g (0.084 mmole) of CuI, 0.155 g (0.22 mmole) of bis(triphenylphosphine)palladium(II)dichloride in 15 ml of THF and 15 ml of triethylamine. The light brown solution turned to a suspension within a minute. After ˜40 min, the reaction mixture turned to an orange solution with some white ppt. The reaction was followed by TLC. The mixture was stirred at room temperature under nitrogen overnight. TLC showed presence of staring material still. The reaction was stirred continuously overnight at room temp. Not much further reaction had occurred. It was then stirred overnight at 50° C. TLC indicated that only a trace of starting material was present. The reaction was then terminated and the reaction mixture was filtered and the filtrate concentrated under reduced pressure. The residue was redissolved in 15 ml of chloroform and the solution was washed two times with water (15 ml each) and dried over anhydrous MgSO4, filtered and concentrated. 2.27 g (90.4% yield) of solid was obtained. 1HNMR: 0.26 ppm (s, 9H); 3.83 ppm (s, 6H); 6.49 ppm (s, 1H); 6.70 ppm (s, 2H); 7.47 ppm (s, 4H). Into a 100 ml round bottom flask was placed The reaction was stirred continuously overnight at room temp Not much further reaction It was then stirred overnight at 50° C The reaction was then terminated the reaction mixture was filtered the filtrate concentrated under reduced pressure The residue was redissolved in 15 ml of chloroform the solution was washed two times with water (15 ml each) dried over anhydrous MgSO4 filtered concentrated

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

Procedure: Into a 50 ml round bottom flask was placed a mixture of 0.64 g (0.0054 mole) of 4-methylphenylacetylene, 1.50 g (0.005 mole) of 4-iodophenyltrimethylsilylacetylene, 0.011 g (0.0058 mmole) of CuI, 0.103 g (0.146 mmole) of bis(triphenylphosphine)palladium(II)dichloride in 10 ml of THF and 10 ml of triethylamine. The brown solution turned to an orange-yellow suspension when solid started to form. The mixture was stirred at room temperature under nitrogen for 3 days. It was filtered and the filtrate concentrated under reduced pressure. The residue was redissolved in 25 ml of chloroform and the solution was washed two times with water (15 ml each) and then dried over anhydrous MgSO4, filtered and concentrated, 1.43 g (quantitative yield) of solid was obtained. 1HNMR indicated ˜10% of by product present. The solid product was used for the next step without further purification. Into a 50 ml round bottom flask was placed to form It was filtered the filtrate concentrated under reduced pressure The residue was redissolved in 25 ml of chloroform the solution was washed two times with water (15 ml each) dried over anhydrous MgSO4 filtered concentrated

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

Procedure: Into a 50 ml round bottom flask was placed a mixture of 0.64 g (0.0054 mole) of 4-methylphenylacetylene, 1.50 g (0.005 mole) of 4-iodophenyltrimethylsilylacetylene, 0.011 g (0.0058 mmole) of CuI, 0.103 g (0.146 mmole) of bis(triphenylphosphine)palladium(II)dichloride in 10 ml of THF and 10 ml of triethylamine. The brown solution turned to an orange-yellow suspension when solid started to form. The mixture was stirred at room temperature under nitrogen for 3 days. It was filtered and the filtrate concentrated under reduced pressure. The residue was redissolved in 25 ml of chloroform and the solution was washed two times with water (15 ml each) and then dried over anhydrous MgSO4, filtered and concentrated, 1.43 g (quantitative yield) of solid was obtained. 1HNMR indicated ˜10% of by product present. The solid product was used for the next step without further purification. Into a 50 ml round bottom flask was placed to form It was filtered the filtrate concentrated under reduced pressure The residue was redissolved in 25 ml of chloroform the solution was washed two times with water (15 ml each) dried over anhydrous MgSO4 filtered concentrated

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

Procedure: Into a 50 ml round bottom flask was placed a mixture of 0.64 g (0.0054 mole) of 4-methylphenylacetylene, 1.50 g (0.005 mole) of 4-iodophenyltrimethylsilylacetylene, 0.011 g (0.0058 mmole) of CuI, 0.103 g (0.146 mmole) of bis(triphenylphosphine)palladium(II)dichloride in 10 ml of THF and 10 ml of triethylamine. The brown solution turned to an orange-yellow suspension when solid started to form. The mixture was stirred at room temperature under nitrogen for 3 days. It was filtered and the filtrate concentrated under reduced pressure. The residue was redissolved in 25 ml of chloroform and the solution was washed two times with water (15 ml each) and then dried over anhydrous MgSO4, filtered and concentrated, 1.43 g (quantitative yield) of solid was obtained. 1HNMR indicated ˜10% of by product present. The solid product was used for the next step without further purification. Into a 50 ml round bottom flask was placed to form It was filtered the filtrate concentrated under reduced pressure The residue was redissolved in 25 ml of chloroform the solution was washed two times with water (15 ml each) dried over anhydrous MgSO4 filtered concentrated

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

Procedure: Into a 50 ml round bottom flask was placed a mixture of 0.72 g (0.0054 mole) of p-methoxyphenylacetylene, 1.51 g (0.005 mole) of 4-iodophenyltrimethylsilylacetylene, 0.0102 g (0.0053 mmole) of CuI, 0.102 g (0.146 mmole) of bis(triphenylphosphine)palladium(II)dichloride in 10 ml of THF and 10 ml of triethylamine. The light orange brown mixture was stirred at room temperature under nitrogen for 3 days. The reaction mixture was then filtered and the filtrate concentrated under reduced pressure. The residue was redissolved in 10 ml of chloroform and the solution was washed two times with water (10 ml each) and then dried over anhydrous MgSO4, filtered and concentrated. 1.5 g (98.7% yield) of solid was obtained. 1HNMR: 0.28 ppm (s, 9H); 3.85 ppm (s, 3H); 6.90 ppm (d, 2H); 7.45 ppm (s, 4H); 7.48 ppm (d, 2H). Into a 50 ml round bottom flask was placed The reaction mixture was then filtered the filtrate concentrated under reduced pressure The residue was redissolved in 10 ml of chloroform the solution was washed two times with water (10 ml each) dried over anhydrous MgSO4 filtered concentrated

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

Procedure: 4-iodophenytrimethyl silylacetylene (5.0 g, 16.6 mmol), 4-n-butylphenylacetylene (2.67 g, 16.0 mmol), CuI (32 mg, 0.16 mmol), bis(triphenylphosphine)palladium(II)dichloride (0.35 g, 0.48 mmol), triethylamine (50 mL) and THF (50 mL) were added together and stirred at ambient temperature under N2 for 18 h. The reaction mixture was filtered to remove solids and concentrated to dryness, redissolved in CHCl3, washed with water (2×), brine, dried with MgSO4, filtered, concentrated and the solid recrystallized from hexanes to give 2.10 g (40%) product. The crude product could also be purified by washing with MeOH. This gave 1.94 g additional product for a total yield of 79%. 1H NMR (CDCl3) δ: 7.46 (m, 6H), 7.20 (d, J=8.11 Hz, 2H); 2.63 (t, J=7.6 Hz, 2H); 1.62 (m, 2H); 1.38 (m, 2H); 0.95 (t, J=7.2 Hz, 3H); 0.28 (s, 9H). 13C {1H} NMR (CDCl3): 143.7, 131.9, 131.6, 131.3, 128.5, 123.6, 122.7, 120.1, 104.7, 96.1, 91.6, 88.4, 35.6, 33.4, 22.3, 14.0, −0.1 ppm. The reaction mixture was filtered to remove solids concentrated to dryness redissolved in CHCl3 washed with water (2×), brine dried with MgSO4 filtered concentrated the solid recrystallized from hexanes

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

Procedure: As shown in the following Reaction 3, 580 mg (4.08 mmol) of 3.4-ethylenedioxythiophene was melted in 10 mL of tetrahydrofuran under nitrogen atmosphere at the temperature of −78° C., and 2.45 mL (6.12 mmol, 1.5 eq) of n-butyllithium was added thereto, and then the reaction solution was stirred for 1 hour. After completion of stirring, 1.37 g (6.12 mmol, 1.5 eq) of zinc bromide was again added to the reaction solution at the temperature of 0° C., and then the reaction solution was stirred for 1 hour. Next, 1.22 g (4.08 mmol, 1 eq) of 4-trimethylsilylethynyl iodobenzene and 110 mg (0.16 mmol, 0.04 eq) of dichlorobis-(triphenylphosphine)palladium(II) were added to the reaction solution, and then the reaction solution was stirred for 12 hours at room temperature. After solvents of the reaction solution were removed by distillation under reduced pressure, the compound distilled under reduced pressure was purified with an alumina column chromatography (mobile phase volume ratio: methylene chloride:n-hexane=2:3) to obtain 740 mg of [4-(2,3-Dihydro-thieno[3,4-b][1,4]dioxin-5-yl)-phenylethynyl]-trimethyl-silane with the yield of 58%. NMR data of the obtained compound is as follows. [1H NMR (400 MHz, CDCl3): δ 0.25 (s, 9H), 4.23-4.24 (m, 2H), 4.30-4.32 (m, 2H), 6.32 (s, 1H), 7.44 (d, 2H), 7.64 (d, 2H)]. was added After completion of stirring the reaction solution was stirred for 1 hour the reaction solution was stirred for 12 hours at room temperature After solvents of the reaction solution were removed by distillation under reduced pressure the compound distilled under reduced pressure was purified with an alumina column chromatography (mobile phase volume ratio: methylene chloride:n-hexane=2:3)

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

Procedure: As shown in the following Reaction 3, 580 mg (4.08 mmol) of 3.4-ethylenedioxythiophene was melted in 10 mL of tetrahydrofuran under nitrogen atmosphere at the temperature of −78° C., and 2.45 mL (6.12 mmol, 1.5 eq) of n-butyllithium was added thereto, and then the reaction solution was stirred for 1 hour. After completion of stirring, 1.37 g (6.12 mmol, 1.5 eq) of zinc bromide was again added to the reaction solution at the temperature of 0° C., and then the reaction solution was stirred for 1 hour. Next, 1.22 g (4.08 mmol, 1 eq) of 4-trimethylsilylethynyl iodobenzene and 110 mg (0.16 mmol, 0.04 eq) of dichlorobis-(triphenylphosphine)palladium(II) were added to the reaction solution, and then the reaction solution was stirred for 12 hours at room temperature. After solvents of the reaction solution were removed by distillation under reduced pressure, the compound distilled under reduced pressure was purified with an alumina column chromatography (mobile phase volume ratio: methylene chloride:n-hexane=2:3) to obtain 740 mg of [4-(2,3-Dihydro-thieno[3,4-b][1,4]dioxin-5-yl)-phenylethynyl]-trimethyl-silane with the yield of 58%. NMR data of the obtained compound is as follows. [1H NMR (400 MHz, CDCl3): δ 0.25 (s, 9H), 4.23-4.24 (m, 2H), 4.30-4.32 (m, 2H), 6.32 (s, 1H), 7.44 (d, 2H), 7.64 (d, 2H)]. was added After completion of stirring the reaction solution was stirred for 1 hour the reaction solution was stirred for 12 hours at room temperature After solvents of the reaction solution were removed by distillation under reduced pressure the compound distilled under reduced pressure was purified with an alumina column chromatography (mobile phase volume ratio: methylene chloride:n-hexane=2:3)

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

Procedure: As shown in the following Reaction 3, 580 mg (4.08 mmol) of 3.4-ethylenedioxythiophene was melted in 10 mL of tetrahydrofuran under nitrogen atmosphere at the temperature of −78° C., and 2.45 mL (6.12 mmol, 1.5 eq) of n-butyllithium was added thereto, and then the reaction solution was stirred for 1 hour. After completion of stirring, 1.37 g (6.12 mmol, 1.5 eq) of zinc bromide was again added to the reaction solution at the temperature of 0° C., and then the reaction solution was stirred for 1 hour. Next, 1.22 g (4.08 mmol, 1 eq) of 4-trimethylsilylethynyl iodobenzene and 110 mg (0.16 mmol, 0.04 eq) of dichlorobis-(triphenylphosphine)palladium(II) were added to the reaction solution, and then the reaction solution was stirred for 12 hours at room temperature. After solvents of the reaction solution were removed by distillation under reduced pressure, the compound distilled under reduced pressure was purified with an alumina column chromatography (mobile phase volume ratio: methylene chloride:n-hexane=2:3) to obtain 740 mg of [4-(2,3-Dihydro-thieno[3,4-b][1,4]dioxin-5-yl)-phenylethynyl]-trimethyl-silane with the yield of 58%. NMR data of the obtained compound is as follows. [1H NMR (400 MHz, CDCl3): δ 0.25 (s, 9H), 4.23-4.24 (m, 2H), 4.30-4.32 (m, 2H), 6.32 (s, 1H), 7.44 (d, 2H), 7.64 (d, 2H)]. was added After completion of stirring the reaction solution was stirred for 1 hour the reaction solution was stirred for 12 hours at room temperature After solvents of the reaction solution were removed by distillation under reduced pressure the compound distilled under reduced pressure was purified with an alumina column chromatography (mobile phase volume ratio: methylene chloride:n-hexane=2:3)

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

Procedure: As shown in the following Reaction 2, 250 mg (1.32 mmol) of 4-trimethylsilylethynylaniline obtained in A of Example 1-1 was melted in 3 mL of hydrochloric acid at the temperature of 0° C., and 94 mg (1.37 mmol, 1.04 eq) of sodium nitrite was added thereto, and then the reaction solution was stirred for 1 hour. After completion of stirring, 280 mg (1.69 mmol, 1.28 eq) of potassium iodide was added to the reaction solution, and then the reaction solution was stirred at room temperature for 12 hours. Next, the reaction solution was extracted with ether 2 times and 1 time with 1M sodium chloride aqueous solutions 1 time. The organic solvent layer was dehydrated with magnesium sulfate, filtered, and then distilled under reduced pressure. The compound distilled under reduced pressure was purified with an alumina column chromatography (mobile phase: hexane) to obtain 360 mg of 4-trimethylsilylethynyl iodobenzene with the yield of 92%. NMR data of the obtained compound is as follows. [1H NMR (400 MHz, CDCl3): δ 0.23-0.27 (m, 9H), 7.16 (d, 2H), 7.69 (d, 2H)]. obtained in A of Example 1-1 was added After completion of stirring the reaction solution was stirred at room temperature for 12 hours Next, the reaction solution was extracted with ether 2 times and 1 time with 1M sodium chloride aqueous solutions 1 time filtered distilled under reduced pressure The compound distilled under reduced pressure was purified with an alumina column chromatography (mobile phase: hexane)