| 99.5% |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine |
|
| 99% |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; for 2h; |
|
| 99% |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; for 2h; Inert atmosphere; |
|
| 99% |
With copper (I) iodide; tetrakis-(triphenylphosphine)-palladium; triethylamine at 20℃; for 4h; Inert atmosphere; |
5.1
A 5 L four-necked round-bottom flask was charged with 250 g (884 mmol) of 1-bromo-2-iodobenzene and 8.4 g (44.2 mmol) of copper iodine,20.4 g (18 mmol) of Pd (PPh3) 4 And dissolved in 1000 ml of triethylamine.After dissolving all the reactants, 116.4 g (1060 mmol) of phenylacetylene was added under nitrogen,Is slowly added to the dropping funnel and stirred at room temperature for 4 hours.After completion of the reaction, dilute with 2000 ml of normal hexane. Filter the reaction mixture into a Buchner vacuum funnel filled with 1.5-2 kg of silica gel, remove the catalyst and salts, and wash with 5 L of n-hexane. The yellow oil is obtained by removing all the solvent of the filtered solution. (225 g, 99% yield) |
| 99% |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; for 2h; Inert atmosphere; Sealed tube; |
|
| 99% |
With copper (I) iodide; tetrakis-(triphenylphosphine)-palladium at 20℃; for 4h; Inert atmosphere; |
2.1 (1) Synthesis of Compound Represented by Formula 2-a
A compound represented by the formula (2-a) was synthesized by the following reaction scheme (12).A flask was charged with 250 g (884 mmol) of 1-bromo-2-iodobenzene, 8.4 g (44.2 mmol) of copper iodide and 20.4 g (18 mmol) of Pd(PPh3)4. After dissolving all the reactants, 116.4 g (1060 mmol) of phenylacetylene was slowly added to the dropping funnel under nitrogen and the mixture was stirred at room temperature for 4 hours. After the reaction was completed, the reaction mixture was filtered through a Buchner vacuum funnel filled with 1.5-2 kg of silica gel by adding 2000 mL of normal hexane to remove the catalyst and salts, and washed with 5 L of n-hexane. The yellow oil was obtained by removing all the solvent of the filtered solution. (225 g, 99% yield) |
| 99% |
With copper (I) iodide; tetrakis-(triphenylphosphine)-palladium; triethylamine In tetrahydrofuran at 20℃; for 14h; Schlenk technique; Inert atmosphere; |
|
| 99% |
Stage #1: 1-Bromo-2-iodobenzene With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine for 0.25h; Inert atmosphere; Schlenk technique;
Stage #2: 1-ethynylbenzene at 20℃; for 18h; Inert atmosphere; Schlenk technique; |
|
| 99% |
Stage #1: 1-Bromo-2-iodobenzene With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine for 0.25h; Inert atmosphere; Schlenk technique;
Stage #2: 1-ethynylbenzene at 20℃; for 24h; Inert atmosphere; Schlenk technique; |
|
| 99% |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; for 5h; Schlenk technique; Inert atmosphere; |
|
| 98% |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; for 4h; |
|
| 98% |
With copper (I) iodide; tetrakis-(triphenylphosphine)-palladium; triethylamine at 20℃; for 1h; Inert atmosphere; |
1.1 (1-A-1) Synthesis of 2-bromobiphenylacetylene
2-Bromo-iodo-benzene (10 g, 35 mmol),Pd (PPh3) 4 (0.8 g, 0.5 mmol),CuI (0.54 g, 1 mmol) was added to 50 mL of triethylamine and stirred well at room temperature.(The reaction proceeds in a nitrogen atmosphere),Phenylacetylene (3.6 mL, 35 mmol) was slowly added.After stirring for about 1 hour at room temperature, 300 mL of hexane was added to terminate the reaction,The whole solution was passed through silica gel to separate the product,The column was even lowered with 500 mL of hexane.The solvent was removed to give a white product (yield: 98%). |
| 98% |
With copper (I) iodide; tetrakis-(triphenylphosphine)-palladium; triethylamine at 20℃; for 1h; Inert atmosphere; |
1.1.1-1 (1-1) Synthesis of 2-bromobiphenylacetylene
2-bromo-iodo-benzene (10 g, 35 mmol), Pd (PPh3) 4 (0.8 g, 0.5 mmol) and CuI (0.54 g, 1 mmol) were added to 50 mL of triethylamine and stirred at room temperature. Mix well.(The reaction proceeds in a nitrogen atmosphere) and phenylacetylene (3.6 mL, 35 mmol) was added slowly.After stirring for 1 hour at room temperature, 300 mL of hexane was added to terminate the reaction. The whole solution was passed through silica gel to separate the product and the column was even lowered to 500 mL of hexane.The solvent was removed to give a white product. (Yield 98%) |
| 98% |
Stage #1: 1-Bromo-2-iodobenzene With copper (I) iodide; tetrakis-(triphenylphosphine)-palladium; triethylamine at 20℃; Inert atmosphere;
Stage #2: 1-ethynylbenzene at 20℃; for 1h; Inert atmosphere; |
1.1-1 Synthesis of (1-A-1) 2-bromobiphenylacetylene
2-bromo-iodo-benzene (10 g, 35 mmol), Pd (PPh3) 4 (0.8 g, 0.5 mmol) and CuI (0.54 g, 1 mmol) were added to 50 mL of triethylamine and stirred at room temperature. The mixture was mixed well (the reaction proceeded in a nitrogen atmosphere), and phenylacetylene (3.6 mL, 35 mmol) was slowly added thereto.After stirring for 1 hour at room temperature, 300 mL of hexane was added to terminate the reaction. The whole solution was passed through silica gel to separate the product. The column was even lowered with 500 mL of hexane. The solvent was removed to give a white product. (Yield 98%) |
| 98% |
With copper (I) iodide; tetrakis-(triphenylphosphine)-palladium; triethylamine at 20℃; for 1h; Inert atmosphere; |
1.1
2-bromo-iodo-benzene (10 g, 35 mmol), Pd (PPh 3) 4 (0.8 g, 0.5 mmol), CuI (0.54 g, 1 mmol)50 mL of triethylamine was added to the mixture and stirred at room temperature. The reaction was carried out in a nitrogen atmosphere.Slowly add phenyl acethylene (3.6mL, 35mmol)After stirring for 1 hour at room temperature, 300 mL of hexane was added to terminate the reaction. The whole solution was passed through silica gel to separate the product, and the column was even lowered with 500 mL of hexane. The solvent was removed to give a white product. (Yield 98%) |
| 98% |
With piperidine; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide In toluene at 45℃; for 4h; |
|
| 98% |
With copper (I) iodide; tetrakis-(triphenylphosphine)-palladium; triethylamine at 20℃; for 1h; Inert atmosphere; |
1.1-1.1-A.1-A-1 (1-A-1) Synthesis of 2-bromobiphenylacetylene
2-Bromo-iodo-benzene (10 g, 35 mmol), Pd (PPh3) 4(0.8 g, 0.5 mmol) and CuI (0.54 g, 1 mmol) were added to 50 mL of triethylamine and stirred well at room temperature and stirred.(The reaction proceeds in a nitrogen atmosphere), and phenylacetylene (3.6 mL, 35 mmol) is slowly added.After stirring at room temperature for about 1 hour, 300 mL of hexane was added to terminate the reaction, and the entire solution was passed through silica gel to separate the product.The column was even lowered with 500 mL of hexane. The solvent was removed to obtain a white product. (Yield 98%) |
| 98% |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; for 0.5h; Inert atmosphere; |
1 Synthesis method of intermediate 2-1
Add o-bromoiodobenzene (52.2g, 184.5mmol) to the flask,Phenylacetylene (18.85g, 184.5mmol) and triethylamine (260mL),Under nitrogen protection,Cuprous iodide (0.35g, 1.84mmol) and triphenylphosphine palladium chloride (0.5g, 0.7mmol) were added. After stirring at room temperature for 0.5h, the reaction was stopped, filtered, and triethylamine was concentrated to obtain 46.8g of yellow oil. Liquid, yield 98%. |
| 98% |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; for 0.5h; Inert atmosphere; |
1 Synthesis method of intermediate CQ1-1:
Add o-bromoiodobenzene (52.2g, 184.5mmol) to the flask,Phenylacetylene (18.85g, 184.5mmol) and triethylamine (260mL),Under nitrogen protection, add cuprous iodide (0.35g, 1.84mmol)And triphenylphosphine palladium chloride (0.5g, 0.7mmol),After stirring the reaction at room temperature for 0.5h, the reaction was stopped,filter,Concentrate off the triethylamine,46.8g of yellow oily liquid was obtained,The yield is 98%. |
| 97% |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In tetrahydrofuran at 20℃; for 9h; Inert atmosphere; |
|
| 97.08% |
With copper (I) iodide; tetrakis-(triphenylphosphine)-palladium; triethylamine at 20℃; for 2h; |
1 Synthesis Example 1. Synthesis of compound represented by formula 16
In a 1000 mL three-necked round bottom flask, add 68 g (0.24 mole) of 1-bromo-2-iodobenzene, 2.29 g (0.012 mole) of CuI and 5.56 g (0.005 mole) of Pd(PPh3)4 and dissolve in 250 mL of Triethylamine.After dissolving all the reactants, 34.32 mL (0.312 mole) of phenyl acethylene was added dropwise and the mixture was stirred at room temperature for 2 hours.The solid was confirmed to be formed and diluted with 500 mL of n-hexane. The glass filter was filled with silica gel, and the reaction solution was filtered to remove the catalyst and the salt. The product was separated by column chromatography to obtain 1-(1) (60 g, 97.08%). |
| 96% |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In neat liquid at 20℃; Inert atmosphere; |
|
| 95% |
Stage #1: 1-Bromo-2-iodobenzene With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; for 0.25h; Inert atmosphere;
Stage #2: 1-ethynylbenzene at 20℃; for 4h; Inert atmosphere; |
|
| 95% |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine |
|
| 95% |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; for 3h; Schlenk technique; Inert atmosphere; |
|
| 95% |
Stage #1: 1-Bromo-2-iodobenzene With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; for 0.25h; Inert atmosphere;
Stage #2: 1-ethynylbenzene at 20℃; for 4h; Inert atmosphere; |
|
| 95% |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; for 3h; Inert atmosphere; |
|
| 95% |
Stage #1: 1-Bromo-2-iodobenzene With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; for 0.166667h; Inert atmosphere;
Stage #2: 1-ethynylbenzene at 20℃; Inert atmosphere; |
1.2 (2) Synthesis of reaction substrate I
5.54 g (19.58 mmol) of o-bromoiodobenzene, 0.28 g (0.39 mmol) of bistriphenylphosphine palladium dichloride,0.19 g (19.58 mmol) of cuprous iodide was added to 30 ml of triethylamine, and the reaction was carried out at room temperature for 10 min under nitrogen protection.2.15 ml (19.58 mmol) of phenylacetylene was slowly added dropwise, and the reaction was stirred at room temperature overnight, followed by TLC until the reaction was completed.The organic phase was washed with water, dried, and rotary evaporated. The crude product was separated by column chromatography (eluent is petroleum ether) to obtain 4.76 g of 1-bromo-2-(phenylethynyl)benzene, with a yield of 95%. |
| 95% |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; for 0.5h; Inert atmosphere; |
6 Preparation of Intermediate A-1
Under argon protection, raw material f-93 (380.00 mmol, 107.50 g), raw material g-93 (380.00 mmol, 38.81 g) and triethylamine (520 mL) were added to the reaction flask, and CuI (3.80 mmol, 0.72 g) was added. ) and Pd(PPh3)2Cl2 (1.4mmol, 0.98g), the reaction was stopped after stirring at room temperature for 0.5 hours, filtered and concentrated to remove triethylamine to obtain intermediate A-1 (92.82g, yield 95%). |
| 94% |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In tetrahydrofuran at 0 - 20℃; for 5h; Inert atmosphere; |
|
| 93% |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide In triethylamine at 24℃; for 16h; Inert atmosphere; |
|
| 92% |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine for 8h; Inert atmosphere; |
|
| 92% |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine Inert atmosphere; |
|
| 92% |
Stage #1: 1-Bromo-2-iodobenzene With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine for 0.166667h; Inert atmosphere;
Stage #2: 1-ethynylbenzene at 20℃; for 6h; Inert atmosphere; |
|
| 92% |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 50℃; for 3h; Inert atmosphere; |
3.1; 6.1
Add 1-bromo-2-iodobenzene (2.70g, 10.0mmol) in a three-necked flask, replace the nitrogen, add 8mL of triethylamine to dissolve, then add bistriphenylphosphonium dichloride (700.0mg, 1mmol) and Cuprous iodide (190.0 mg, 1 mmol), and finally phenylacetylene (2.04 g, 20.0 mmol, 2.20 mL) was added. The reaction was carried out at 50°C for 3 hours, washed with saturated ammonium chloride solution, extracted with ethyl acetate, dried over anhydrous sodium sulfate, concentrated under reduced pressure and separated by column chromatography to obtain colorless crystals 6, with a yield of 92%. |
| 91% |
With piperidine; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide In benzene at 80 - 90℃; for 12.5h; |
|
| 91% |
With piperidine; copper (I) iodide In acetonitrile at 80℃; for 20h; |
|
| 91% |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In tetrahydrofuran at 0 - 20℃; for 5h; |
|
| 90% |
With Cs2CO3; 2‐hydroxybenzoic acid; copper chloride (II) In N,N-dimethyl-formamide at 130℃; for 24h; Inert atmosphere; |
|
| 90% |
Stage #1: 1-Bromo-2-iodobenzene With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide In triethylamine for 0.25h; Inert atmosphere;
Stage #2: 1-ethynylbenzene In triethylamine for 12h; Inert atmosphere; |
|
| 90% |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine for 6.08333h; Inert atmosphere; |
|
| 90% |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; Inert atmosphere; |
182.A Example 182
Step A: 2-Iodobromobenzene (0.065 mL, 0.50 mmol), copper iodide (7.6 mg, 0.04 mmol, 0.08 eq), PdCl2(PPh3)2 (35 mg, 0.05 mmol, 0.1 eq) were placed in a reaction vial under an atmosphere of argon. A solution of phenylacetylene (0.055 mL, 0.5 mmol, 1 eq) in triethylamine (5 mL) was added to the vial and the reaction was stirred at room temperature for several hours. Upon conversion of the starting material by TLC, the reaction was quenched with an aqueous ammonium chloride solution and extracted with ethyl acetate. The organic layers were combined and washed with brine, dried over sodium sulfate, and concentrated to afford a crude oil. The crude oil was purified by column chromatography (100% hexanes) to provide as 1-bromo-2-(phenylethynyl)benzene a clear oil (115 mg, 90% yield). |
| 90% |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In tetrahydrofuran at 20℃; for 12h; Schlenk technique; Inert atmosphere; |
|
| 89% |
Stage #1: 1-Bromo-2-iodobenzene With copper (I) iodide; triethylamine at 23℃; for 0.25h; Inert atmosphere;
Stage #2: With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) for 0.25h; Inert atmosphere;
Stage #3: 1-ethynylbenzene at 20℃; for 12h; Inert atmosphere; |
|
| 89% |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; for 12h; Inert atmosphere; |
Synthesis of 1-bromo-2-(phenylethynyl)benzene (S-12)
Synthesis of 1-bromo-2-(phenylethynyl)benzene (S-12) 2-bromoiodobenzene (1.00 g, 3.53 mmol) was added in one portion to a solution of CuI (0.07 g, 10 mol %) in Et3N (30 mL) and degassed with nitrogen for 15 min at 23° C. PdCl2(PPh3)2 (0.12 g, 5 mol %) was added to the mixture and was stirred for 15 min before being treated with ethynylbenzene (0.40 g, 3.88 mmol) dropwise. The resulting solution was stirred at room temperature for 12 h and then filtered through a celite pad, concentrated, and eluted through a silica column to give the desired synthesis of 1-bromo-2-(phenylethynyl)benzene (S-12) (0.80 g, 3.14 mmol, 89%). |
| 89% |
Stage #1: 1-Bromo-2-iodobenzene With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine for 0.25h; Inert atmosphere;
Stage #2: 1-ethynylbenzene at 20℃; for 12h; Inert atmosphere; |
|
| 88% |
With tetrahydropyrrole; air In lithium hydroxide monohydrate at 50℃; for 24h; |
|
| 88% |
Stage #1: 1-Bromo-2-iodobenzene With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine for 0.166667h; Inert atmosphere;
Stage #2: 1-ethynylbenzene With triethylamine for 12.0833h; Inert atmosphere; |
|
| 88% |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine for 12h; |
|
| 88% |
Stage #1: 1-Bromo-2-iodobenzene With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine for 0.166667h;
Stage #2: 1-ethynylbenzene With triethylamine for 12h; |
1 Example 1: General procedure for sonogashira cross coupling of aryl iodides with different substituted acetylenes
General procedure: A suspension of (un)substituted 2-bromoiodobenzene (2 gm, 7.06 mmol), PdCl2(PPh3)2 (99.2 mg, 0.14 mmol, 2 mol%), Cu(I) iodide (40.2 mg, 0.21 mmol, 3 mol%) in 20 mL of triethylamine was degassed three times. After 10 min a solution of (un)substituted aryl/alkyl acetylene (0.84 mL, 7.77 mmol, 1.1 eq) in Et3N (3.6 mL) is added dropwise over 5 min via syringe and the reaction mixture is left to stir for 12 h and monitored by TLC. After total consumption of the 2-bromoiodobenzene, the reaction mixture was filtered through celite and extracted with EtOAc (3 x 10 mL). The organic layer was washed with a saturated solution of NH4C1 (2 x 10 mL), water (2 x 10 mL), dried over Na2S04 and the solvent was removed under vacuo. The reaction mixture was purified by flash chromatography on silica gel, (eluent: pet. ether) to give the product (un)substituted bromo benzene as a yellow oil (SI, Yield 88%). |
| 88% |
With copper (I) iodide; potassium carbonate; ethylene glycol In N,N-dimethyl acetamide at 110℃; for 24h; |
2.6 Typical procedure for sonogashira reaction
General procedure: Aromatic iodide (1.0mmol), alkyne (2.0mmol), K2CO3 (3.0mmol), glycol (0.2g) and CuI (0.02mmol) were added into a tubular reactor containing 15mgPdCPVC fiber mat and 3.2mL DMAc. The reaction was carried out at 110°C with magnetic stirring. The post treatment was the same as that of PdCPVC catalyzed Heck reaction. The coupling products were confirmed by the 1H NMR spectra and mass spectra. |
| 87% |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; for 18h; |
|
| 85% |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide In triethylamine at 20℃; for 24h; |
|
| 84% |
With copper (I) iodide; tetrakis-(triphenylphosphine)-palladium; N-butylamine In tetrahydrofuran at 70℃; for 11h; Inert atmosphere; |
|
| 84% |
With copper (I) iodide; tetrakis-(triphenylphosphine)-palladium; N-butylamine In tetrahydrofuran at 70℃; for 11h; Inert atmosphere; |
Step 1. Preparation of 1-bromo-2-(phenylethynyl)benzene (B).
Toa solution of compound 7 (1 g, 3.53mmol) in THF, Pd(PPh3)4 (0.05 eqv.), CuI (0.1 eqv.), BuNH2(1.4 eqv.) and phenyl acetylene (1.2 eqv.) were added successively under argon atmosphere.The mixture was stirred at 70 0C for 11 h. After completion of reaction(monitored by TLC), the mixture was cooled and solvent was evaporated underreduced pressure. To this mixture water was added (20 mL), then extracted withdichloromethane and dried over anhydrous Na2SO4. Thecrude compound was purified using silica gel (60-120 mesh) columnchromatography (petroleum ether/EtOAc) to afford compound 8 (760 mg, 84 %) as colorless liquid.1H NMR (500 MHz, CDCl3): δ 7.09 (t, J = 7.0 Hz, 1H), 7.11-7.31 (m, 4H), 7.46-7.54 (m, 4H) ppm. 13C NMR (125 MHz, CDCl3): δ 88.2, 94.1, 122.0, 127.2, 128.5, 128.6, 128.8, 129.4, 129.5, 131.9,132.6, 132.7, 133.4 ppm. |
| 82% |
Stage #1: 1-Bromo-2-iodobenzene With 1-(1H-benzotriazol-1-ylmethyl)-1H-benzotriazole; palladium diacetate In dimethyl sulfoxide at 20℃; for 0.25h;
Stage #2: 1-ethynylbenzene With potassium carbonate In dimethyl sulfoxide at 80℃; for 8h; |
|
| 82% |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; Inert atmosphere; |
|
| 81% |
With copper oxide (I); Cs2CO3 In N,N-dimethyl-formamide at 135℃; for 24h; Inert atmosphere; |
General Procedure for the Synthesis of Compounds 3a-e
General procedure: A sealable vial equipped with a magnetic stir bar wascharged with Cs2CO3 (652 mg, 2.0 mmol) and Cu2O (7.0 mg,0.05 mmol) under a nitrogen atmosphere. The aperture of thevial was then covered with a rubber septum. Under a nitrogen atmosphere, aryl alkyne 1 (1.5 mmol), aryl iodide 2 (1.0 mmol), and DMF (0.5 mL) were added by syringe. The septum was then replaced by a screw cap containing a Teflon-coated septum, and the reaction vessel was placed at 135 °C. After stirring at this temperature for 24 h, the heterogeneous mixture was cooled to r.t. and diluted with EtOAc (20 mL). The resulting solution was filtered through a pad of silica gel, then washed with EtOAc (20 mL), and concentrated to give the crude material which was then purified by column chromatography on silica gel to yield alkyne 3. |
| 80% |
With tetrahydropyrrole; palladium (II) chloride In lithium hydroxide monohydrate at 50℃; for 24h; |
|
| 80% |
With tetrahydropyrrole; palladium (II) chloride In lithium hydroxide monohydrate at 50℃; for 24h; |
|
| 78% |
With C19H25CuN5(1+)*F6P(1-); potassium carbonate In N,N-dimethyl-formamide at 135 - 140℃; Sealed tube; |
4.4 Cu-catalyzed coupling of aryl iodide and phenylacetylene derivatives
General procedure: A 20mL scintillation vial was charged with a Teflon stir bar, copper complex (0.1mmol), 76 potassium carbonate (0.75mmol), aryl iodide (0.5mmol), 77 phenylacetylene (0.75mmol) in 5mL non-anhydrous DMF in air. The vial was sealed and placed in an oil bath with pre-adjusted temperature at 135-140°C. After the allowed time, the reaction mixture was cooled down, diluted with 25-30mL ethyl acetate, and filtered through a pad of silica gel. The solvent was then removed under vacuum and the residue was purified by column chromatography using mixtures of hexane and ethyl acetate to obtain analytically pure product. |
| 75% |
Stage #1: 1-Bromo-2-iodobenzene With triethylamine at 20℃; for 0.5h; Inert atmosphere;
Stage #2: 1-ethynylbenzene With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide at 20℃; for 24h; Inert atmosphere; |
|
| 74% |
Stage #1: 1-Bromo-2-iodobenzene With triethylamine at 20℃; for 0.5h;
Stage #2: 1-ethynylbenzene With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide at 20℃; for 24h; |
|
| 67% |
With C10H24Cl2N2Pd2Se2; triethylamine In 1,4-dioxane at 100℃; for 12h; Schlenk technique; |
General experimental procedure for the reaction
General procedure: Inan oven dried 25 ml Schlenk tube add a mixture of aryl halide (1mmol),arylacetylene (1.2 mmol), Pd catalyst 1d (3mol%), triethyl amine (2mmol) in 4ml dioxane. The reaction mixture was heated in an oil bath at 100oCfor 12 h with continuous stirring. After 12 h the reaction mixture was cooledto room temperature and the product was extracted with ethyl acetate (3 x10ml). After drying over Na2SO4, the solvent was removedunder vacuum, and the resulting crude product was purified by columnchromatography on silica gel. The product was eluted with petroleum ether:ethyl acetate (10.0:0.0 to 9.5:0.5) solvent system. |
| 65% |
With triethylamine In lithium hydroxide monohydrate at 20℃; for 6h; |
2.3 General procedure for the Sonogashira cross-coupling reaction of aryl iodides
General procedure: A mixture of aryl iodide (1.0mmol), phenylacetylene (1.2mmol), Et3N (2.0mmol) and 0.005mmol (10mg) of Pd(II) complex 4 was stirred at room temperature for a desired reaction time. Further, the reaction mixture was extracted with ethyl acetate and dried over MgSO4. The solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel using hexane as eluent to give the corresponding coupling products. |
| 65% |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In tetrahydrofuran at 23℃; for 16h; Inert atmosphere; |
|
| 64.3% |
With copper (I) iodide; C36H30O2P2Pd In triethylamine at 20℃; for 24h; Inert atmosphere; |
1.1
Under the protection of nitrogen, to the 100 ml reaction tube joining the 78 mg (0.11mmol) b (triphenylphosphine) - palladium dioxide, 1.06g (3.75mmol) neighbouring bromine monoiodo-benzene, 25 ml triethylamine, 24 mg (0.13mmol) CuI and 0.383g (3.75mmol) such as the structural formula (1 - 1) indicated by the phenylacetylene, room temperature stirring 24h, filtration, filtrate with ethyl ether extraction, washing, drying, steaming and, in order to developing agent is pure hexane column chromatographic separation, shall be 0.62g (yield 64.3%) 1 - bromo -2 - phenyl ethynylbenzene, the 1 - bromo -2 - phenyl ethynylbenzene structural formula such as formula (1 - 2) is shown. |
| 63% |
With piperidine; copper (I) iodide; bis(triphenylphosphine)dichloropalladium In benzene at 60℃; for 18h; Inert atmosphere; |
|
| 63% |
With palladium diacetate; potassium carbonate In ethanol at 80℃; for 24h; |
|
| 62.1% |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 60℃; for 5h; |
1 Preparation of the compound 1
1-bromo-2-iodobenzene (50 g, 176.7 mmol), phenylacetylene (21.7 g, 212.5 mmol) and triethylamine (800 ml) were placed in a 2 L round bottom flask and stirred. Bis (triphenylphosphine) palladium dichloride (2.48 g, 3.54 mmol) and cuprous iodide (0.34 g, 1.79 mmol) were added and stirred at 60 ° C. for 5 hours. The mixture was cooled to room temperature, and the formed solid was filtered. The filtered liquid was distilled under reduced pressure, concentrated, and purified by column to obtain Compound 1 (28.2 g, 109.7 mmol) in a yield of 62.1% |
| 55% |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In tetrahydrofuran at 20℃; for 2h; Inert atmosphere; |
5 Synthesis of intermediate 1-c
7.5g (1.2eq) of 2-bromoiodobenzene,780 mg (0.05 eq) of bis(chloro(triphenylphosphine))palladium (PdCl2(PPh3)2) and 250 mg (0.06 eq) of CuI were mixed together in a flask.Nitrogen is supplied under vacuum,Then add 70 mL of THF to the mixture and stir.then,13 mL (8 eq) of triethylamine and 2.2 g (1 eq) of Intermediate 1-1 were slowly added dropwise thereto,And then it was stirred at room temperature for 2 hours under N2 pressure.Evaporate using a rotary evaporator to remove the solvent.After adding 50mL of water,The reaction solution was extracted three times with 50 mL of ether.The organic layer was collected and dried using magnesium sulfate to evaporate the solvent.The residue was separated and purified using silica gel column chromatography.3.1 g of intermediate 1-c was obtained (yield: 55%).This compound was identified using LC-MS. |
| 53% |
With tripotassium phosphate tribasic; C48H42Cu4N8O9*(x)H2O In N,N-dimethyl-formamide at 150℃; for 18h; Inert atmosphere; Schlenk technique; |
|
|
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In 1,4-dioxane at 40℃; for 1 - 2h; |
|
|
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; Inert atmosphere; |
|
|
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; N,N-diisopropylamine In tetrahydrofuran |
|
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With copper (I) iodide; trans-bis(triphenylphosphine)palladium(II) dichloride; diethylamine at 20℃; Inert atmosphere; |
|
|
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; for 3.5h; |
|
|
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In N,N-dimethyl-formamide at 80℃; Inert atmosphere; Schlenk technique; |
|
|
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; diethylamine In N,N-dimethyl-formamide at 20℃; Inert atmosphere; |
General procedure 2 (GP2) for the synthesis of o-(alkynyl)-(3-methylbut-2-enyl)benzenes 1:
General procedure: Step 1: A mixture of 1-bromo-2-iodobenzene (7 mmol, 1.98 g), the corresponding alkyne (8.4 mmol), PdCl2(PPh3)2 (3 mol %, 148 mg), CuI (5 mol %, 66.5 mg) and Et2NH (10.5 mmol, 1.25 mL), in anhydrous DMF (28 mL) was stirred under a nitrogen atmosphere at rt until complete consumption of starting material, as monitored by S6TLC or GC-MS (3-6 h). CH2Cl2 and water were added to the reaction mixture and the aqueous phase was extracted with CH2Cl2. The combined organic layers were washed with water, dried over anhydrous Na2SO4 and concentrated at reduced pressure. The remaining residue was purified by column chromatography on silica gel using mixtures of hexane and ethyl acetate as eluent to afford the corresponding o-alkynylbromobenzenes (74-97%) which were used in the next step. |
|
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In tetrahydrofuran |
|
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With copper (I) iodide; tetrakis-(triphenylphosphine)-palladium at 20℃; Inert atmosphere; |
|
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With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); triethylamine In N,N-dimethyl-formamide at 25℃; for 0.5h; Inert atmosphere; Sealed tube; |
|
|
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; Inert atmosphere; |
|
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With palladium diacetate; Cs2CO3; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In N,N-dimethyl-formamide at 20℃; for 3h; Schlenk technique; Inert atmosphere; |
|
| 9 g |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; for 24h; |
2 Preparation Example 2 Preparation of Compound 5 Preparation of Compound 5-1
337 mg (1.77 mmol) of CuI and 744 mg (1.06 mmol) of Pd (PPh 3) 2 Cl 2 were dissolved in 150 ml of triethylamineTo this solution were added 3.2 g (31.8 mmol) of phenylacetylene, 1-bromo-2-iodobenzene 10G (35.3 mm & lt; 3 & gt;) were sequentially added thereto, followed by stirring at room temperature for 24 hours. After completion of the reaction, the reaction mixture was washed with ammonium chloride solution,Acetate. The solution was distilled under reduced pressure, and the column was separated and purified to obtain 9.1 g (35.0 mmol) of the compound 5-1 |
|
With copper (I) iodide; tetrakis-(triphenylphosphine)-palladium at 20℃; for 6h; Inert atmosphere; Schlenk technique; |
|
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With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; for 10h; Inert atmosphere; |
|
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With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine for 8h; Inert atmosphere; |
|
| 87 %Spectr. |
With potassium carbonate In N,N-dimethyl acetamide; ethylene glycol at 110℃; for 5h; |
General Procedure for the Sonogashira Reaction
General procedure: Pd(at)CS/PEO fiber mat (50 mg, palladium contentof 4.9 μmol) was added to the N,N-dimethylacetamide solution containing glycol (0.2 g), aromatic halide (0.7 mmol), phenylene acetylene (1.4 mmol) and K2CO3 (3.0 mmol). The reaction was carried out at 110°C and monitored by TLC and GC-MS analysis. After completion, the reaction mixture was quenched with 10 mL H2O. The Pd(at)CS/PEO was recovered by simple filtration and the filtrate was extracted three times (3 × 20 mL) by ethyl acetate. The combined organic layer was concentrated to ∼5 mL and then purified by silica gel chromatography to afford the coupling product. |
|
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; diethylamine In N,N-dimethyl-formamide at 50℃; for 24h; Inert atmosphere; |
|
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With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; Inert atmosphere; |
|
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With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; for 2h; |
|
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With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; for 12h; Inert atmosphere; |
A Step A:
Add 10 mmol o-iodobromobenzene, 10.5 mmol phenylacetylene, 0.25 mmol PdCl2(PPh)2, 0.50 mmol cuprous iodide, and 100 mL triethylamine into the reactor. In a nitrogen atmosphere, the reaction is stirred at room temperature for 12 hours.After the reaction, the mixture was poured into ethyl acetate and washed with saturated brine. After the aqueous layer was extracted with ethyl acetate, the organic layers were combined (that is, the organic layer after washing and the organic layer obtained by extraction) were combined. The water was dried over sodium sulfate, the solvent was distilled off under reduced pressure, and the crude product was purified by flash column chromatography (petroleum ether) to obtain the product 1-bromo-2-(phenylethynyl)benzene. |
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