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Structure of 4-Bromophenylacetonitrile
CAS No.: 16532-79-9
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
4.5
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| CAS No. : | 16532-79-9 |
| Formula : | C8H6BrN |
| M.W : | 196.04 |
| SMILES Code : | BrC1=CC=C(CC#N)C=C1 |
| English Name : | 4-Bromophenylacetonitrile |
| MDL No. : | MFCD00001916 |
| InChI Key : | MFHFWRBXPQDZSA-UHFFFAOYSA-N |
| Pubchem ID : | 27914 |
| GHS Pictogram: | |
| Signal Word: | |
| Hazard Statements: | |
| Precautionary Statements: | |
| Class: | |
| UN#: | |
| Packing Group: |
| Num. heavy atoms | 10 |
| Num. arom. heavy atoms | 6 |
| Fraction Csp3 | 0.12 |
| Num. rotatable bonds | 1 |
| Num. H-bond acceptors | 1.0 |
| Num. H-bond donors | 0.0 |
| Molar Refractivity | 43.66 |
| TPSA ? Topological Polar Surface Area: Calculated from |
23.79 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.89 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.53 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.52 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.52 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.81 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.45 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-3.03 |
| Solubility | 0.184 mg/ml ; 0.000939 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-2.68 |
| Solubility | 0.413 mg/ml ; 0.00211 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.74 |
| Solubility | 0.0353 mg/ml ; 0.00018 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
| BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
| P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
| CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
| CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
| CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
| CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
| CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
| Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.7 cm/s |
| Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
| Ghose? Ghose filter: implemented from |
None |
| Veber? Veber (GSK) filter: implemented from |
0.0 |
| Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
| Muegge? Muegge (Bayer) filter: implemented from |
2.0 |
| Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
| PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
| Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
| Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
| Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.16 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

[ 26421-44-3 ]
[ 16532-79-9 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 92% | With iodine; sodium methylate In methanol; diethyl ether at -78 - 0℃; for 6h; Inert atmosphere; | Experimental procedure and spectroscopic data for 2,3-bis(4-bromophenyl)fumaronitrile (10) A mixture of 4-bromophenylacetonitrile 5 (2.50 g, 12.5 mmol) and iodine (3.20 g, 12.5 mmol) was purged with N2 and dry Et2O (80 mL) was added via syringe. A solution was cooled to -78 °C. Sodium methoxide (1.40 g, 25 mmol) and methanol (10 mL) were slowly added over a period of 30 min and stirred for another 30 min. The solution was then placed in an ice-water bath with vigorous stirring at 0 °C for a further 5 h, before 5% hydrochloric acid (50 mL) was added dropwise at a temperature lower than 10 °C. The solution was filtered to isolate the precipitate, which was rinsed with a cold methanol/water solution (50:50) to give a white solid in 92% yield; mp = 213-215 °C; 1H NMR (300 MHz, CDCl3), δ (ppm): 7.68-7.75 (m, 8H); 13C NMR (75 MHz, CDCl3): δ (ppm): 115.59, 124.14, 126.30, 129.59, 130.08, 132.19. |
| 90% | With iodine; sodium methylate In methanol; diethyl ether at -78 - 0℃; | |
| 90% | With iodine; sodium methylate In methanol; diethyl ether at -78 - 0℃; |
| 90% | With iodine; sodium methylate In methanol; diethyl ether at -78 - 0℃; for 4.5h; | |
| 90% | Stage #1: 4-Bromophenylacetonitrile With iodine; sodium methylate In methanol; diethyl ether at -78 - 0℃; for 5.2h; Inert atmosphere; Stage #2: With hydrogenchloride In methanol; diethyl ether; water | |
| 90% | With iodine; sodium methylate In methanol; diethyl ether at -78 - 20℃; for 12h; | Compound 1 General procedure: Sodium methoxide (4 mmol) - methanol solution was slowly added to a solution of 4 (1.0 g, 2.12 mmol) and I2 (0.51 g, 2.01 mmol) in dry diethyl ether at -78°C. The reaction mixture was stirred for 12 h at rt. The crude product was filtered and washed with water and methanol. The residue was purified by silica gel column chromatography. The pure 1 was obtained by size-exculsion chromatography (JAIGEL-2H and 1H, CHCl3). Title compound was obtained as an orange solid (200 mg, 20%). |
| 86% | With sodium bromide In methanol at 0℃; Electrolysis; | |
| 82% | With potassium carbonate In dimethyl sulfoxide at 20℃; for 1.5h; | |
| 80% | With iodine; sodium methylate In methanol; diethyl ether at -78 - 0℃; for 4h; Inert atmosphere; | |
| 72% | With iodine; sodium methylate In methanol; diethyl ether at -78 - 0℃; Inert atmosphere; | |
| 63% | With iodine; oxygen; sodium methylate In methanol; diethyl ether; water at -78 - 0℃; for 3h; Inert atmosphere; | Compound 1: P-Bromophenylacetonitrile (5 g, 25.505 mmol) and iodine (6.5734 g, 25.505 mmol) were placed in a 250 mL reaction flask and the mixture was purged with argon three times until the bottle had no oxygen and water.A solution of sodium methoxide (2.8933 g, 5.356 mmol) in anhydrous methanol (8.680 g, 14.613 ml) was added dropwise to the above solution at -78 ° C under oxygen and water, and the whole drop was maintained Argon atmosphere.After the dropwise addition, the temperature was gradually raised to 0 ° C, and the reaction was continued for 3 hours.After the reaction, the reaction was quenched with a 5% dilute hydrochloric acid solution, and the reaction was stirred for 12 hours.After the reaction was complete, the solution was filtered and the filter cake was washed twice with methanol and water.The resulting solid was dried in a vacuum oven.The final product was white powder compound 1 (3.1143 g, 63% yield). |
| 48% | With iodine; sodium methylate In methanol; diethyl ether at -78℃; Inert atmosphere; | |
| 45% | Stage #1: 4-Bromophenylacetonitrile With iodine In diethyl ether at -78 - 0℃; for 0.5h; Inert atmosphere; Stage #2: With sodium methylate In methanol; diethyl ether at 0 - 20℃; for 24h; | 4 Preparation of intermediate compound [213-1] After the 250 mL reaction flask was placed in a 2- (4-bromophenyl) acetonitrile 10.00g (20.27mmol) in a nitrogen atmosphere to a reaction vessel, iodine 3.32g (20.27mmol), 68 mL of diethyl ether into a -78 stirred at for 30 minutes and slowly raised the temperature to 0 . Here the sodium methoxide 49.20g (42.58mmol) was added dropwise slowly after dissolved in 40 mL of methanol, theThe reaction was slowly raising the temperature to room temperature for 24 hours. This was added to 100 mL 3% HCl solution was slowly stirred for 2 hours, the reaction was terminated. Extracted with 100 mL ethyl acetate, separated and purified by silica gel chromatography to give the intermediate compound [213-1] 3.54g (45%) of off-white solid. |
| With diethyl ether; iodine; sodium ethanolate | ||
| With iodine; sodium methylate In diethyl ether at -78 - 0℃; for 4.5h; | ||
| With iodine; sodium methylate at -78℃; | ||
| With iodine; sodium In methanol; diethyl ether at 20℃; Cooling with ice; Inert atmosphere; | 2.2.1. General procedure for the synthesis of 1-6 General procedure: Phenylacetonitrile derivatives (1 mmol) and iodine (0.25 g, 1 mmol)were dissolved in 5 mL of dry diethyl ether. Sodium methoxide solutionnewly prepared from sodium (0.05 g, 2.1 mmol) and 5 mL of methanolwas added slowly (over a period of 30 min) into the reaction solution atdry ice temperature under a nitrogen atmosphere. The reaction solutionwas allowed to warm by replacing the dry ice bath with an ice-water bath before the temperature rose to above 0 °C. The reaction solutionwas stirred for another 3-4 h at room temperature, and then the reactionwas quenched with 3-6% hydrochloric acid at less than 10 °C, andfiltered to isolate the solid which was rinsed with cold methanol-watersolution to wash away ionic substances. The reaction mixture was extractedwith ethyl acetate, washed by saturated brine and then over anhydrous MgSO4. After the solvent was removed under reducedpressure, the crude product was purified by column chromatography orrecrystallization to give the pure product. | |
| 86 % | With sodium bromide In methanol at 0℃; Electrolysis; | 2.2.1. General electrolysis procedure General procedure: A solution of phenylacetonitrile (10 mmol) and sodium bro- mide (0.52 g, 5 mmol) in methanol (20 mL) was electrolyzed in an undivided cell equipped with a magnetic stirrer, a graphite anode and an iron cathode at 0 °C under a constant cur- rent density of 100 mA cm -2 ( I = 500 mA, electrodes square 5 cm 2 ) until 2.5 F mol -1 (for the preparation of 2 and 2,3-di(4- bromophenyl)fumaronitrile) or 2.8 F mol -1 (for the preparation of 1 ) of electricity was passed. After the electrolysis was finished, the solution was filtered to isolate the solid product, which was then rinsed with an ice-cold methanol/water solution (9:1, 2 mL), and dried under reduced pressure. |
| 85 % | With iodine; sodium methylate In diethyl ether at -78 - -10℃; Inert atmosphere; | 2.2. Synthesis of 2,3-bis(4-bromophenyl) fumaronitrile (2) Under nitrogen atmosphere, 2-(4-bromophenyl) acetonitrile (5.00 g,25.64 mmol), I2 (6.45g, 25.64 mmol) and ether (130 mL) were added toa 200 mL round bottom flask in sequence. The system was cooled to 78 C, CH3ONa (10.20 mL, 51.24 mmol) was added dropwise, andstirred at 10 C for 5 h, and then cooled down to room temperature.The mixture was extracted with CH2Cl2 (100 mL × 3) and then dried andconcentrated. The solid mixture was purified by column chromatography(CH2Cl2/petroleum ether (v/v = 1/2) as eluent) to obtain 4.0 gfaint yellow solid (compound 2) with a yield of 85 %. 1H NMR (600MHz, CDCl3) δ (ppm): 7.75 7.62 (m, 8H). HR-MS (C16H8Br2N2,[M]+): Calculated: 388.9057; Found: 388.9081. |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 100% | Stage #1: 4-Bromophenylacetonitrile With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; Inert atmosphere; Stage #2: isopropyl bromide In N,N-dimethyl-formamide; mineral oil for 16h; Inert atmosphere; Heating; | |
| Stage #1: 4-Bromophenylacetonitrile With sodium hydride In N,N-dimethyl-formamide; mineral oil for 0.25h; Stage #2: isopropyl bromide In N,N-dimethyl-formamide; mineral oil at 20℃; for 2h; | To a solution of R-1 (20.0 g, 0.102 mol) in DMF (300 mL) at 0 °C is added NaH (60% in oil suspension, 4.28 g, 0.107 mol) slowly. The mixture is then stirred for a further 15 minutes and 2-bromopropane (9.60 mL, 0.107 mol) is added. The reaction mixture is allowed to warm to room temperature, stirring continued for 2 hours and then concentrated in vacuo. The residue is partitioned between CH2CI2 and brine. The combined organics are dried with Na2S04, filtered and concentrated in vacuo. The residue is purified by flash chromatography (Si02, 0-15% EtOAc in heptane) to give 1-1 (21.3 g); m/z 238.3, 240.2 [M/M+2H] | |
| 21.3 g | Stage #1: 4-Bromophenylacetonitrile With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.25h; Stage #2: isopropyl bromide In N,N-dimethyl-formamide; mineral oil at 20℃; for 2h; | Synthesis of 2-(4-bromo-phenyl)-2,3-dimethylbutyronitrile To a solution of R-1 (20.0 g, 0.102 mol) in DMF (300 mL) at 0° C. is added NaH (60% in oil suspension, 4.28 g, 0.107 mol) slowly. The mixture is then stirred for a further 15 minutes and 2-bromopropane (9.60 mL, 0.107 mol) is added. The reaction mixture is allowed to warm to room temperature, stirring continued for 2 hours and then concentrated in vacuo. The residue is partitioned between CH2Cl2 and brine. The combined organics are dried with Na2SO4, filtered and concentrated in vacuo. The residue is purified by flash chromatography (SiO2, 0-15% EtOAc in heptane) to give I-1 (21.3 g); m/z 238.3, 240.2 [M/M+2H] |
| Stage #1: 4-Bromophenylacetonitrile With Lithium 1,1,1,3,3,3-hexamethyldisilazide In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: isopropyl bromide In tetrahydrofuran for 16h; Inert atmosphere; | ||
| With sodium hydride |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With sodium amide |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 44% | With sodium azide; ammonium chloride In N,N-dimethyl-formamide at 90℃; for 48h; | |
| With hydrogenchloride; ammonium chloride In water; N,N-dimethyl-formamide | 8 Preparation of 5-[(4-bromophenyl)methyl]-2H-tetrazole EXAMPLE 8 Preparation of 5-[(4-bromophenyl)methyl]-2H-tetrazole 4-Bromophenylacetonitrile (30.0 g, 0.15 mol), sodium azide (10.9 g, 0.17 mol) and ammonium chloride (8.9 g, 0.17 mol) were heated in DMF (300 mL) at 90° C. for 2 days. After concentration, water (200 mL) was added to the residue, the mixture was basified with 1M NaOH (170 mL) and washed with ether (2*100 mL). Acidification of the aqueous layer with 1N HCl and collection of the precipitate by suction filtration produced the crude product. This was purified by recrystallization from ethanol to provide 5-[(4-bromophenyl)methyl]-2H-tetrazole (17.2 g, 0.07 mol) in 44% yield, mp. 173°-175° C. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 92% | With sodium In ethanol for 10h; Heating; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 90% | ||
| 85% | Stage #1: benzophenone With sodium hydride In toluene; mineral oil at 110℃; for 0.166667h; Inert atmosphere; Stage #2: 4-Bromophenylacetonitrile In toluene; mineral oil for 20h; Inert atmosphere; | 1 Preparation of Compound IV. To a 100 mL two-necked round-bottom flask, 4.0 g (22 mmol) of benzophenone and 1.0 g (25 mmol) of 60% NaH were added. Under nitrogen protection at 110°C, 20 mL of anhydrous toluene was added and stirred for 10 minutes. A solution of 4-bromophenylacetonitrile (3.92 g, 20 mmol) in 5 mL of toluene was added dropwise to the above mixture over 60 minutes. After 20 hours, the mixture was cooled to room temperature. The organic layer was extracted with dichloromethane, dried with anhydrous sodium sulfate, and purified by column chromatography (DCM:PE = 2:1). Finally, recrystallization yielded 6.12 g of a pale yellow solid with a yield of 85%. |
| 84% | Stage #1: benzophenone With sodium hydride In toluene; mineral oil at 80℃; for 0.166667h; Inert atmosphere; Stage #2: 4-Bromophenylacetonitrile In toluene at 80℃; |
| 80% | In benzene for 20h; Heating; | |
| 76% | Stage #1: benzophenone With sodium hydride In toluene for 0.166667h; Inert atmosphere; Reflux; Stage #2: 4-Bromophenylacetonitrile In toluene for 21h; Inert atmosphere; Reflux; | |
| 53% | Stage #1: benzophenone With sodium hydride In tetrahydrofuran at 70℃; for 0.166667h; Inert atmosphere; Stage #2: 4-Bromophenylacetonitrile In tetrahydrofuran at 70℃; for 24h; Inert atmosphere; | |
| 37% | Stage #1: benzophenone With sodium hydride In toluene; mineral oil at 110℃; for 0.166667h; Inert atmosphere; Stage #2: 4-Bromophenylacetonitrile In toluene; mineral oil for 21h; Reflux; Inert atmosphere; | 2.1 2.2.1. 2-(4-Bromophenyl)-3,3-diphenylacrylonitrile [40] Into a 250 mL three-necked round bottom flask equipped with a condenser, benzophenone (4.65 g, 25.5mmol), sodium hydride (60% NaH) (5 g, 128 mmol) and toluene (150 mL) were placed under argon. The mixture was stirred at 110°C for 10 min. A solution of 4-bromobenzylnitrile (5 g, 25.5 mmol) in toluene (150 mL) was dropwise added into the above mentioned mixture over a period of ∼60min while maintaining reflux. After 20h the mixture was cooled to room temperature, and water (100 mL) was added. The organic layer was collected and washed three times with brine solution. The organic phase was dried over anhydrous MgSO4 and concentrated under vacuum. The residue was purified by silica gel chromatography (eluent: dichloromethane/hexane=3/7) followed by recrystallization from ethanol to give the desired product as a light yellow solid in 37% yield (3.4 g). 1H NMR (400MHz, CDCl3) δ (ppm) 7.61 - 7.42 (m, 5H), 7.42 - 7.36 (m, 2H), 7.36 - 7.30 (m, 1H), 7.28 - 7.23 (m, 2H), 7.23 - 7.15 (m, 2H), 7.06 (dd, J=8.4, 1.0Hz, 2H). 13C NMR (100MHz, CDCl3) δ (ppm) 158.18, 139.96, 138.53, 133.66, 131.52, 131.10, 130.49, 129.92, 129.71, 129.11, 128.32, 128.28, 122.39, 119.50, 110.22. MS (GCMS): m/z calcd 360.2; found 361.0. |
| With sodium hydride In benzene Reflux; | ||
| With sodium hydride In toluene | ||
| 5.1 g | Stage #1: benzophenone With sodium hydride In benzene for 0.166667h; Glovebox; Inert atmosphere; Sealed tube; Reflux; Stage #2: 4-Bromophenylacetonitrile In benzene for 21h; Glovebox; Inert atmosphere; Sealed tube; Reflux; | 2-(4-Bromophenyl)-3,3-diphenylacrylonitrile (3) A three neck flask (100 mL) equipped with a Teflon coated stir bar was charged with benzophenone 1 (3.2 g, 18.3 mmol), NaH (0.5 g, 21 mmol), and benzene (20 mL) while working in an inert atmosphere glovebox. A separate liquid addition funnel was charged with 4-bromobenzylnitrile 2 (3.7 g, 19.1 mmol) and benzene (30 mL). The funnel and the round-bottom flask were temporarily sealed with rubber septa, then assembled outside of the box against a counter flow of dry N2. While maintaining the inert atmosphere, a reflux condenser was then added to the assembly. The benzophenone/NaH mixture was heated to reflux for 10 min, then the 4-bromobenzylnitrile 2 was added dropwise over 60 min while maintaining reflux. Evolving gas (H2) was observed at the oil bubbler and the reaction was allowed to proceed for 20 h. Upon cooling to room temperature, the reaction mixture was diluted with water and the organic phase was separated and washed with brine (3 × 100 mL). The organic phase was then dried (MgSO4) and concentrated under vacuum. Addition of methanol gives a pale yellow powder that was filtered off and washed with additional methanol, then dried under vacuum. Yield 5.1 g (79%). 1H NMR (600 MHz, TMS, CDCl3) δ = 7.44-7.40 (m, 5H), 7.33 (d, J = 8.4 Hz, 2H), 7.27 (t, J = 12.0, 7.2 Hz, 1H), 7.21 (t, J = 8.4 Hz, 2H), 7.12 (d, J = 9.0 Hz, 2H), 6.99 (d, J = 7.8 Hz, 2H) (Fig. S4); 13C NMR (150 MHz, CDCl3) δ (ppm) = 158.34, 140.07, 138.65, 133.75, 131.64, 131.20, 130.62, 130.04, 129.82, 129.22, 128.44, 128.39, 122.50, 119.65, 110.31 (Fig. S5); HRMS (ESI/TOF-Q): m/z [M+Na]+ calcd for C21H14BrNNa 382.0207, found 384.0188 (Fig. S6). |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 94.2% | With sodium bromide at 150℃; for 3h; Inert atmosphere; Autoclave; | 1-3 Synthesis of Intermediate 1: Under nitrogen, p-bromophenylacetonitrile (120 g, 0.61 mol), dimethyl carbonate (439 g, 4.88 mol), and sodium bromide (94.7 g, 0.92 mol) were added to an autoclave. The autoclave was sealed and heated to 150°C. The reaction was allowed to proceed at a pressure of 2 MPa for 3 h. After completion of the reaction, the reaction solution was cooled to room temperature, filtered, and washed with toluene.The filtrate was concentrated to obtain Intermediate 1 in a yield of 94.2%. |
| With potassium carbonate at 180℃; for 16h; | ||
| With potassium carbonate at 180℃; for 16h; autoclave; | 30 Intermediate 30; 2-(4-Bromo-phenyl)-propionitrile; An autoclave is charged with 25.0 g (128 mmol) 4-bromobenzylcyanide, 190 mL dimethylcarbonate and 0.900 g (6.51 mmol) K2CO3 and stirred for 16 h at 180° C. Then the reaction mixture is allowed to cool to r.t., the mixture is diluted with EtOAc and washed with water (1×), aq. 10% Na2S2O3 solution (1×) and brine (1×). The organic layer is dried with MgSO4 and the solvent is removed in vacuo. The residue is purified by destillation (bath temperature 204° C., head temperature 153° C.).C9H8BrN (M=210.1 g/mol)Rf (TLC): 0.25 (silica gel, CyH/EtOAc 9/1) |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 57% | With sodium hydroxide;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; for 2h;Heating / reflux; | 5-ISO-BUTYL-2-(N-TERT-BUTYLAMINOSULFONYL) THIOPHENE-3-BORONIC acid (200.5 mg, 0.628 mmol; see Example 1 (C) above), 4-bromophenylacetonitrile (81.7 mg, 0.416 mmol), toluene (15 mL), ethanol (2.5 mL), NAOH (1.0 M, 1.5 mL, 1.5 mmol) and Pd (PPh3) 4 (18 MG, 0.016 mmol) were mixed together under N2. The mixture was heated at reflux for 2 hours and then diluted with EtOAc (50 mL). The organic phase was washed with water and brine, then dried over MGS04. The solvent was removed in vacuo and the residue was separated by column chromatography using hexane: acetone (4: 1) to give the sub-title compound (92.5 mg, 0.237 mmol, yield: 57%). IR (neat): 3291, 2996, 2868,2243, 1510, 1464, 1425 cm-1. 1H NMR S (CDC13) : 7.65 (2H, d, J= 8.2), 7.42 (2H, d, J= 8.2), 6.75 (1H, s), 3. 81 (2H, s), 2.70 (2H, d, J= 7.1), 1.97 (1H, m), 1. 01 (9H, s), 0.98 (6H, d, J = 6. 9). 132C NMR No.(CDCL3) : 148.6, 142.3, 134.8, 130.1, 129.8, 128.8, 128.0, 117.6, 54.6, 39.2, 30.6, 29.6, 23.5, 22.1. MS (ESI+) M/Z : 390.8 Anal. Calcd. for C2OH26N202S2. 1/AXH20 : C, 60.12 ; H, 6.81 ; N, 7.01. Found: C, 60.5 ; H, 6.6 ; N, 6.9. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With sodium hydride In tetrahydrofuran at 0 - 60℃; | ||
| Stage #1: 4-Bromophenylacetonitrile With sodium hydride In tetrahydrofuran; mineral oil for 0.0833333h; Stage #2: ethyl acetate In tetrahydrofuran; mineral oil at 60℃; | ||
| With sodium In tetrahydrofuran at 80℃; |
| Stage #1: 4-Bromophenylacetonitrile With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 1h; Inert atmosphere; Stage #2: ethyl acetate In tetrahydrofuran; mineral oil for 12h; Inert atmosphere; |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1: NaNH2 2: KOH |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With NaH In water; N,N-dimethyl-formamide; benzene | 1.A (4-bromophenyl)(cyclohexyl)acetonitrile EXAMPLE 1A (4-bromophenyl)(cyclohexyl)acetonitrile A suspension of NaH (1.1 g, 27.5 mmol) in DMF (15 mL) and benzene (30 mL) at 0° C. was treated dropwise with 4-bromophenylacetonitrile (5.0 g, 25.5 mmol), stirred for 45 minutes, treated portionwise with cyclohexyl bromide (3.15 mL, 25.5 mmol), warmed to room temperature, stirred for 90 minutes, treated with water, and extracted with diethyl ether. The extract was washed with water and brine, dried (Na2SO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 5:1 hexanes/ethyl acetate to provide the desired product. | |
| Stage #1: 4-Bromophenylacetonitrile With Lithium 1,1,1,3,3,3-hexamethyldisilazide In N,N,N,N,N,N-hexamethylphosphoric triamide at -78℃; for 0.5h; Inert atmosphere; Stage #2: 1-bromocyclohexane In N,N,N,N,N,N-hexamethylphosphoric triamide for 16h; Inert atmosphere; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 40.3 g (85%) | With potassium carbonate In ethyl acetate; carbonic acid dimethyl ester | 1 2-(4-Bromophenyl)propionitrile Preparation 1 2-(4-Bromophenyl)propionitrile A solution of 50.0 g (225.0 mmol) of 4-bromophenylacetonitrile and 1.8 g (12.8 mmol) of potassium carbonate in 387 mL of dimethyl carbonate was heated to 180° C. in a sealed vessel for 16 hours. The solution was then cooled, diluted with 200 ml of ethyl acetate and washed once with 100 ml water, once with 100 ml of 10% aqueous sodium bisulfate and once with 100 ml brine. The organic portion was dried (MgSO4), filtered and concentrated in vacuo. The residue was distilled under vacuum through a short path distillation apparatus to afford 40.3 g (85%) of the title compound. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 10 1-(4-Bromophenyl)cyclobutanecarboxylic Acid 1-(4-Bromophenyl)cyclobutanecarboxylic Acid The title compound was prepared in an analogous manner to that in Example 9 from 4-bromophenylacetonitrile and 1,3-dibromopropane. The yield was 6 g (46%); 1 H NMR (CDCl3) δ 1.79-1.94 (m, 1H), 2.00-2.17 (m, 1H), 2.42-2.53 (m, 2H), 2.78-2.88 (m, 2H), 7.17 (d, 2H), 7.45 (d, 2H). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 37% | With caesium carbonate;palladium diacetate; In N,N-dimethyl-formamide; at 90℃; for 18h; | Example 8: Synthesis of 4'-[2-(2-butoxy-5-chlorobenzoylamino)-l-methyl-ethyl]-biphenyl- 4-carboxylic acid (Compound 71); 8.27 Into a 250 mL round-bottomed flask are placed 4-bromophenyl acetonitrile (2.5 g, 12.7 mmol), (4-?-butylcarbonyl)boronic acid (2.82 g, 12.7 mmol), and palladium (II) acetate (0.25 g, 1.11 mmol). A 2 M solution Of Cs2CO3 (10.5 mL) is added to the flask followed by DMF (50 mL) and the mixture is heated at 90 0C for 18 h. The reaction mixture is cooled, diluted with EtOAc (100 mL), and washed with water (5 x 100 mL), 2 M HCl (50 mL), and brine (100 mL). The organic layer is dried over Na2SO4, filtered, concentrated to dryness, and the <n="77"/>resulting residue may be purified by flash silica gel chromatography (eluent: 15percent EtOAc in hexanes) to give 8.27 (1.25 g, 37percent) as a yellow solid. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With sodium hydrogencarbonate In tetrahydrofuran for 24h; Heating / reflux; | 81.i (i) Methyl 2-(4-(cyanomethyl)benzyl)-3-oxobutanoate A stirred mixture of methyl 3-hydroxy-2-methylenebutanoate (19.5g), 2-(4- bromophenyl)acetonitrile (4Og), PdOAc2 (2g), tetrabutylammonium bromide (4Og) and NaHCO3 (31.5g) in THF (300ml) was heated under N2 at reflux for 24h. The mixture was cooled, diluted with ether (500ml) and filtered through celite. The filtrate was washed with water, dried and evaporated under reduced pressure to give an oil, used crude in next step. LC-MS m/z 244 APCI - | |
| With triethylamine In acetonitrile at 70℃; for 6h; Inert atmosphere of nitrogen; | 4c.i; 4d.i Example 4c (i) Methyl 2-(4-(cyanomethyl)benzyl)-3-oxobutanoate A stirred mixture of methyl 3-hydroxy-2-methylenebutanoate (70.0 g), 2-(4- bromophenyl)acetonitrile (126.5 g), PdCl2[P(o-tol)3]2 (4.2 g) and triethylamine (108.9 g) in acetonitrile (280 mL) was heated under nitrogen at 7O0C for 6 hours. The mixture was cooled to room temperature, diluted with toluene (840 mL) and water (840 mL) and stirred for 10 minutes. The organic layer was separated, washed with water (840 mL) and concentrated under reduced pressure to give the subtitle compound as a red oil, 158.7 g. This product was used in the next step without further purification. LC-MS m/z 244 APCI; Example 4d (i) Methyl 2-(4-(cyanomethyl)benzyl)-3-oxobutanoateA stirred mixture of methyl 3-hydroxy-2-methylenebutanoate (30.0 g, 0.23 mol), 2-(4- bromophenyl)acetonitrile (54.2 g, 0.28 mol), PdCl2[P(o-tol)3]2 (1.8 g, 2 mmol) and triethylamine (46.7 g, 0.46 mol) in acetonitrile (90 g) was heated at 70°C for 6 hours under a N2 atmosphere. The mixture was cooled to 250C, diluted with toluene (300 g) and 10% aq. acetic acid (360 g), and stirred for 10 minutes. The organic layer was separated, washed with water (360 g), and concentrated under reduced pressure to give the subtitle compound as a red oil, 67.3 g. This product was used in the next step without further purification. LC-MS m/z 244 APCI |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 93% | With potassium hydroxide In methanol for 4h; Reflux; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 47% | With PPA at 160℃; for 24h; | 1 Step 1. Into a 40-mL round-bottom flask, was placed 4-bromophenylacetonitrile (1.10 g, 5.611 mmol, 1.00 equiv), Paraformaldehyde (556 mg, 6.172 mmol, 1.10 equiv), PPA (6.5g, 56.1 mmol, 10.00 equiv). The resulting solution was stirred for 24h at 160 °C. The resulting solution was diluted with 20 mL of H2O. The pH value of the solution was adjusted to 7-8 with 1M NaHCO3. The resulting solution was extracted with 3x20 mL of ethyl acetate and the organic layers combined and concentrated. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:1). This resulted in 600 mg (47%) of 7-bromo-2,4-dihydro-1H- isoquinolin-3-one as a yellow solid. LCMS: [M+1]+=226. |
| Stage #1: formaldehyd; 4-Bromophenylacetonitrile With pyrophosphoric acid at 170℃; for 0.583333h; Stage #2: With water; sodium carbonate | 2 Parafoϖnaldehyde (1.69 g, 56.1 mmol), 4-broniophenylacetonitrile (10.0 g, 51.0 mmol), and pyrophosphoric acid (48.0 g, 270 mmol) were combined in a round-bottomed flask. The flask was placed in a 170 0C oil bath for 35 minutes, open to the air. Gas evolution was observed, and the mixture slowly turned brown. The hot mixture was poured into ice water (200 mL), quenched with solid sodium carbonate to pH 8 then extracted with dichloromethane (3 x 200 mL). The combined organic fractions were dried (Na2SO4), filtered and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel Biotage 65M, eluting with 0-15% methanol/dichloromethane to afford 7-bromo- 1,4- dihydroisoquinolin-3(2i)-one as a light yellow solid.1H NMR (CDCl3): δ 7.39 (dd, 1 H, J=8.1, 1.8 Hz), 7.33 (s, 1 H), 7.04 (d, 1 H, J=8.1 Hz), 6.96 (br, 1 H), 4.46 (s, 2 H), 3.53 (s, 2 H) MS: m/e 226.08, 228.09 (M+H)+, (M+2+H)+ |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 81% | With potassium acetate; palladium diacetate In N,N-dimethyl acetamide at 150℃; for 12h; Inert atmosphere; | General Procedure: As a typical experiment, the reaction of the aryl bromide (1 mmol), the halothiophene derivative (2 mmol) and KOAc (0.196 g, 2 mmol) at 100-150 °C (see tables or schemes) during 3-20 h (see tables or schemes) in DMAc (4 mL) in the presence of Pd(OAc)2 (see tables or schemes) under argon affords the corresponding product after extraction with dichloromethane, evaporation and filtration on silica gel (pentane/ether). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 90% | With iodine; sodium In methanol; diethyl ether Inert atmosphere; Cooling; | |
| 90% | With iodine; sodium methylate In methanol; diethyl ether at -78 - 0℃; for 5.16667h; Inert atmosphere; | |
| 80% | With iodine; sodium methylate In methanol; diethyl ether at -78 - 20℃; for 4.5h; Inert atmosphere; | 4.1 Step 1, Synthesis of 2,3-di(bromophenyl)fumaronitrile (DBCN-DBr) Step 1, Synthesis of 2,3-di(bromophenyl)fumaronitrile (DBCN-DBr)4-bromophenylacetonitrile (10.0g, 51.0mmol) and iodine (12.9g, 51.0mmol) was dissolved in 200mL anhydrous diethyl ether, stirred at -78°C nitrogen atmosphere, and sodium methoxide was slowly added dropwise (5.5g, 102.0 mmol) in 50mL methanol solution, after 30 minutes, slowly warmed to room temperature and stirring was continued for 4 hours, during this time, the reaction mixture will form more and more precipitate. Then, added to the reaction mixture at 0°C was 2M hydrochloric acid solution to terminate the reaction. Was filtered and after that, the crude product was washed with water and methanol and the precipitate was rinsed several times with n-hexane/dichloromethane (1: 1 by volume) as the mobile phase silica gel as stationary phase for the column chromatography, to obtain 7.9 g of a pale yellow solid, yield 80%; |
| 80% | With iodine; sodium methylate In tetrahydrofuran; methanol; diethyl ether at -78℃; for 4.5h; Inert atmosphere; | 1 Synthesis of M1:In a 100 mL round bottom flask,p-Bromophenylacetonitrile (10 mmol, 1.96 g),Iodine (10mmol, 2.54g) was dissolved in 50mL of tetrahydrofuran, degassed three times, and then dropped into methanol solution of sodium methoxide under nitrogen protection at -78 °C.(20 mmol, 2.0 g), activated for 0.5 h, then the reaction was stirred in an ice-water bath for 4 h. After stopping the reaction, pumping and filtering to produce crudeSeparation by column chromatography using petroleum ether and dichloromethane mixed solvent (1:1 by volume) as a developing solvent to give a white solid(1.6g, yield: 80%) |
| 70% | With iodine; sodium methylate In diethyl ether at -78℃; for 4.5h; Inert atmosphere; Cooling with ice; | Synthesis of 2,3-bis(4-bromophenyl)fumaronitrile (M2) 2-(4-bromophenyl)acetonitrile (1 g, 5.1 mmol) and I2 (1.3 g, 5.1 mmol) were dissolved in diethyl ether under nitrogen. The system temperature was stabilized at -78 °C, and sodium methylate (1.7 g, 10.71 mmol) was added to the reaction system and stirred for 30 min. Then, the reaction mixture was transferred to ice water and stirred for further 4 h.Thereafter, a small amount of 3% HCl (aq) was added to quench the reaction, and then M2 was isolated from the reaction solution by filtration. Yield: 70% |
| 63% | Stage #1: 4-Bromophenylacetonitrile With iodine; sodium methylate In methanol; diethyl ether at 0℃; Inert atmosphere; Cooling; Stage #2: With hydrogenchloride In water for 12h; Inert atmosphere; | |
| 56% | With methanol; iodine; sodium In diethyl ether at -78 - 0℃; for 2.25h; Inert atmosphere; | |
| 38.4% | With iodine; sodium methylate In methanol; diethyl ether at -78 - 0℃; for 4h; | 1-A <Preparation Example 1-A> Synthesis of Monomer (bis (4-bromophenyl) fumaronitrile) 4-bromophenylacetonitrile (23.0 g, 117 mmol) and iodine (29.8 g, 117 mmol) were dissolved in 400 ml of ether,Lower the temperature to -78 ° C. Sodium methoxide (13.3 g, 246 mmol) dissolved in anhydrous methanol at a concentration of 10 wt% is slowly dropped, the temperature is raised to 0 ° C, and the mixture is stirred for 4 hours. After the reaction was completed by adding 5% HCl (Hydrochloric acid) aqueous solution, the mixture was filtered, washed with water and cold methanol, and then recrystallized from chloroform and methanol to obtain a white solid . |
| Stage #1: 4-Bromophenylacetonitrile With iodine; sodium methylate In methanol; diethyl ether at -78 - 0℃; Stage #2: With hydrogenchloride In methanol; diethyl ether; water | ||
| With iodine; sodium methylate In methanol; diethyl ether at -78 - 10℃; for 8.5h; Inert atmosphere; | ||
| Stage #1: 4-Bromophenylacetonitrile With iodine; sodium methylate In methanol; diethyl ether at -78 - 0℃; for 5.5h; Inert atmosphere; Stage #2: With hydrogenchloride In methanol; diethyl ether at 10℃; | 2.1 2.1 the Synthesis of the Aggregation-Induced Emission Compound P-bromophenylacetonitrile (12.5 mmol) and iodine (12.5 mmol) were dissolved in dry ether (80 ml), and then the system was cooled to -78° C. under a nitrogen atmosphere. Subsequently, sodium methoxide (25 mmol) and methanol (10 ml) were gradually added and stirred for 30 minutes. Following, the system was slowly heated to 0° C. and stirred for 5 hours in an ice-water bath. Then, 5% dilute hydrochloric acid (50 ml) was gradually dropped thereto and the temperature of the system was kept below 10° C. when added. After the reaction was completed, the mixture was filtered with suction, and the filter cake was washed with a methanol/water (v/v=1/1) mixed solution, dried and purified by column chromatography to give compound 1. | |
| Electrochemical reaction; | ||
| Stage #1: 4-Bromophenylacetonitrile With iodine; sodium methylate In methanol Stage #2: With hydrogenchloride | ||
| 40 % | With iodine; sodium methylate In methanol; diethyl ether at -78 - 20℃; | 3.S1 Preparation of S1.2,3-bis(4-bromophenyl)fumaronitrile Add 2-(4-bromophenyl)acetonitrile (5g, 25.5mmol) and iodine (8.4g, 33.2mol) into a 250ml two-necked round-bottomed flask at -78°C, dissolve in 100mL ether, vacuum and blow nitrogen ; Dissolve 3.44g of sodium methoxide (63.75mol) into 60mL of methanol, gradually add it dropwise to the flask, and stir at room temperature for 24h.The reaction solution was washed with sodium thiosulfate solution, separated, dried and recrystallized to obtain 2.01 g of 2,3-bis(4-bromophenyl)fumaronitrile (40% yield) |
| 42 % | With iodine; sodium methylate In methanol; diethyl ether at -78 - 0℃; Inert atmosphere; | |
| 32.4 % | With iodine; sodium methylate In diethyl ether at -78 - -10℃; Inert atmosphere; | |
| With iodine; sodium methylate In methanol; diethyl ether at -78℃; Inert atmosphere; | 3,6-dibromophenanthrene-9,10-dicarbonitrile. 2-(4-Bromophenyl)acetonitrile (5 g, 25.5 mmol), iodine (8.4 g, 33.2 mol), and 100 mL of diethyl ether were combined in a 250 mL two-necked flask. The reaction mixture was cooled to -78 °C under a nitrogen atmosphere. Subsequently, a methanol solution of sodium methoxide (3.44 g/63.75 mmol in 60 mL) was added dropwise to the mixture under stirring for 24 h, and the temperature was gradually increased to room temperature. After solvent removal, the resulting solid was extracted with dichloromethane and washed three times with sodium thiosulfate solution. The organic layer was collected and dried with anhydrous MgSO4, yielding a yellow solid (2,3-bis(4-bromophenyl)fumaronitrile) that did not require purification for the subsequent reaction. A catalytic amount of iodine (5 mg, 0.02 mmol) was added to a toluene solution (200 mL) of 2,3-bis(4-bromophenyl)fumaronitrile (2 g, 5.15 mmol). The mixture was subjected to light irradiation using a 150 W high-pressure mercury lamp under stirring at room temperature for 24 h. Afterward, the reaction mixture was poured into water and extracted with dichloromethane. The combined organic extracts were dried over anhydrous MgSO4, filtered, and the solvent was evaporated. The crude product was purified via column chromatography using a petroleum ether/dichloromethane eluent (1:1, v/v), resulting in a yellow solid product (1.5 g) with a yield of 75%. 1H NMR (400 MHz, Chloroform-d) δ 8.67 (s, 2H), 8.37 (s, 2H), 7.88 (s, 2H). | |
| Stage #1: 4-Bromophenylacetonitrile With iodine In diethyl ether at -78℃; Stage #2: With sodium methylate In diethyl ether at 0℃; | ||
| With iodine; sodium methylate In diethyl ether at 0℃; Inert atmosphere; Schlenk technique; |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 97% | Stage #1: 4-Bromophenylacetonitrile With Pd(CH2TMS)2(COD); BrettPhos In toluene at 80℃; for 0.0166667h; Inert atmosphere; Stage #2: silver(I) trifluoromethanethiolate With phenyltriethylammonium iodide In toluene at 80℃; for 2h; Inert atmosphere; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 91% | Stage #1: 4-Bromophenylacetonitrile In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: methyl iodide In tetrahydrofuran for 1h; Inert atmosphere; | |
| 72% | Stage #1: 4-Bromophenylacetonitrile With sodium hydride In tetrahydrofuran at 0 - 20℃; for 1h; Stage #2: methyl iodide In tetrahydrofuran for 14h; | 649 Example 649 2-(4-bromophenyl)propanenitrileTo a solution of 2-(4-bromophenyl)acetonitrile (5.0 g, 25.5 mmol) in anhydrous THF (70 mL) was cooled to 0 °C and sodium hydride (60 wt %, 1.5 g, 38.3 mmol) added portion wise. The mixture was stirred at room temperature for 1 h. After which methyl iodide (1.8 mL, 28.1 mmol) was added and the mixture stirred for 14 h. The reaction mixture was carefully quenched with water at 0 °C and diluted with ethyl acetate (200 mL). The layers were seperated and the organic layer was dried over anhydrous sodium sulfate, filtered, concentrated and the residue purified by column chromatography (silica, 0-30% ethyl acetate/heptane) to afford the desired product (3.8 g, 72%) as a yellow oil: ESI MS m/z 210 [C H8BrN +H]+. |
| 62% | Stage #1: 4-Bromophenylacetonitrile With sodium hydride In tetrahydrofuran; mineral oil at 20℃; for 1h; Stage #2: methyl iodide In tetrahydrofuran; mineral oil at 20℃; for 2h; | 109.1 Step 1. 2-(4-Bromophenyl)propanenitriIe Step 1. 2-(4-Bromophenyl)propanenitriIe (1541) [00487] into a 100-mL round-bottom flask was added 2-(4-bromophenyl)acetonitrile (3.00 g, 15.3 mmol), tetrahydrofuran (30 mL), and sodium hydride (60% by weight; 2.60 g, 65.0 mmol). The reaction mixture was stirred for I h at RT. The reaction mixture was cooled to 0 °C then iodomethane (0.551 g, 0.242 mL, 3.88 mmol) was added and the reaction mixture was stirred at RT for an additional 2 h. The reaction was then quenched by the addition of H2O (10 mL), and then was extracted with dichloromethane (3 30 mL). The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to afford 2-(4- bromophenyi)propanemtrile (2 g, 62%) as a yellow solid. LCMS (ESI, m/z) 210 [M+H]+. |
| 54% | With sodium hexamethyldisilazane In tetrahydrofuran at 0 - 20℃; Inert atmosphere; Schlenk technique; | |
| 53.6% | Stage #1: 4-Bromophenylacetonitrile With sodium hexamethyldisilazane In tetrahydrofuran at 0 - 20℃; Inert atmosphere; Stage #2: methyl iodide In tetrahydrofuran at 20℃; for 1h; | 1 Step 1: To a stirred solution of 2-(4-bromo phenyl) acetonitrile (20 g, 102.04 mmol) in dry tetrahydrofuran (200 mL) was added sodium bis(trimethylsilyl)amide (18.71 g, 102.04 mmol) at 0° C. under a nitrogen atmosphere. After stirring for 20 minutes at room temperature, methyl iodide (14.48 g, 102 mmol) was added and then stirred for 1 h at room temperature. The reaction mixture was quenched with an aqueous ammonium chloride solution and extracted with ethyl acetate (2×150 mL). The combined organic layers were washed with water (2×100 mL), a saturated aqueous sodium chloride solution (2×25 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Flash chromatography (3-4% ethyl acetate/hexanes) afforded 2-(4-bromo-phenyl)-propionitrile as a light yellow liquid (11.5 g, 53.6%). |
| 51.2% | With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; | 64.1 The preparation of 2-(4-bromophenyl)propanenitrile In a round bottom flask, 2-(4-bromophenyl)acetonitrile (1.01 g, 5.15 mmol) was dissolved in DMF (5.15 mL). At 0°C was added 60% sodium hydride (261 mg, 6.53 mmol, 1.27 eq) and methyl iodide (321 uL, 5.15 mmol, 1.0 eq) was added over 30 mm. After 2h stirring at RT, reaction was quenched by addition to cold water. Mixture was extracted with ethyl acetate, washed with saturated sodium chloride, dried over magnesium sulfate, filtered, evaporated. Purification by silica gel chromatography (0-50% ethyl acetate in heptanes as eluent) yielded 2-(4-bromophenyl)propanenitrile (553.5 mg, 51.2% yield). ‘H NMR (400 MHz, CHLOROFORM-d) ö 7.53 (d, I = 8.53 Hz, 2H), 7.25 (d, I = 8.28 Hz, 2H), 3.88 (q, I = 7.28 Hz, 1H), 1.64 (d, I = 7.28 Hz, 3H). |
| 65.13 % | Stage #1: 4-Bromophenylacetonitrile With Lithium 1,1,1,3,3,3-hexamethyldisilazide In tetrahydrofuran at -78℃; Inert atmosphere; Stage #2: methyl iodide In tetrahydrofuran at -78℃; Inert atmosphere; | 1 Step-1: T To a solution of 2-(4-bromophenyl)acetonitrile (2 g, 10.20 mmol, 1.34 mL) in THF (20 mL) was added lithium bis(trimethylsilyl)amide (1 M, 12.24 mL) at -78°C under an atmosphere of argon. The mixture was stirred at -78°C for 0.5 hour, then iodomethane (1.59 g, 11.22 mmol. 698.61 pL) was added, and the mixture was stirred at -78 °C for 2 hours. The reaction mixture was quenched by the addition of ammonium chloride (50 mL) and extracted with ethyl acetate (50 mL*2 ). The combined organic layers were washed with brine (50 mL), dried over Na2SC>4, filtered, and concentrated under reduced pressure. The residue was purified by flash silica gel chromatography (10 g silica, 0-10% ethyl acetate/petroleum ether gradient at 70 mL/min) to give 2-(4-bromophenyl)propanenitrile (1.41 g, 6.64 mmol, 65.13% yield) as a yellow oil. 1H NMR (400 MHz, CDC13) d 7.54-7.52 (m, 2H), 7.27-7.24 (m, 2H), 3.88 (q, J = 7.2 Hz, 1H), 1.65-1.63 (d, J = 7.2 Hz, 3H). |
| 40 % | Stage #1: 4-Bromophenylacetonitrile With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78℃; Inert atmosphere; Stage #2: methyl iodide In tetrahydrofuran; hexane at -78℃; Inert atmosphere; | |
| 65.13 % | Stage #1: 4-Bromophenylacetonitrile With Lithium 1,1,1,3,3,3-hexamethyldisilazide In tetrahydrofuran at -78℃; Inert atmosphere; Stage #2: methyl iodide In tetrahydrofuran at -78℃; Inert atmosphere; | Step-1: To a solution of 2-(4-bromophenyl)acetonitrile (2 g, 10.20 mmol, 1.34 mL) in THF (20 mL) was added lithium bis(trimethylsilyl)amide (1 M, 12.24 mL) at -78°C under an atmosphere of argon. The mixture was stirred at -78°C for 0.5 hour then iodomethane (1.59 g, 11.22 mmol, 698.61 pL) was added, and the mixture was stirred at -78 °C for 2 hours. The reaction mixture was quenched by addition of ammonium chloride (50 mL) and extracted with ethyl acetate (50 mL*2 ). The combined organic layers were washed with brine (50 mL), dried over NaiSCL, filtered, and concentrated under reduced pressure. The residue was purified by flash silica gel chromatography (10 g silica, 0-10% ethyl acetate/petroleum ether gradient at 70 mL/min) to give 2-(4-bromophenyl)propanenitrile (1.41 g, 6.64 mmol, 65.13% yield) as a yellow oil. NMR (400 MHz, CDCh) d 7.54-7.52 (m, 2H), 7.27-7.24 (m, 2H), 3.88 (q, J= 7.2 Hz, 1H), 1.65-1.63 (d, J= 7.2 Hz, 3H). |
| 65.13 % | Stage #1: 4-Bromophenylacetonitrile With Lithium 1,1,1,3,3,3-hexamethyldisilazide In tetrahydrofuran at -78℃; Inert atmosphere; Stage #2: methyl iodide In tetrahydrofuran at -78℃; Inert atmosphere; | Step-1: To a solution of 2-(4-bromophenyl)acetonitrile (2 g, 10.20 mmol, 1.34 mL) in THF (20 mL) was added lithium bis(trimethylsilyl)amide (1 M, 12.24 mL) at -78°C under an atmosphere of argon. The mixture was stirred at -78°C for 0.5 hour then iodomethane (1.59 g, 11.22 mmol, 698.61 pL) was added, and the mixture was stirred at -78 °C for 2 hours. The reaction mixture was quenched by addition of ammonium chloride (50 mL) and extracted with ethyl acetate (50 mL*2 ). The combined organic layers were washed with brine (50 mL), dried over NaiSCL, filtered, and concentrated under reduced pressure. The residue was purified by flash silica gel chromatography (10 g silica, 0-10% ethyl acetate/petroleum ether gradient at 70 mL/min) to give 2-(4-bromophenyl)propanenitrile (1.41 g, 6.64 mmol, 65.13% yield) as a yellow oil. NMR (400 MHz, CDCh) d 7.54-7.52 (m, 2H), 7.27-7.24 (m, 2H), 3.88 (q, J= 7.2 Hz, 1H), 1.65-1.63 (d, J= 7.2 Hz, 3H). |
| Stage #1: 4-Bromophenylacetonitrile With Lithium 1,1,1,3,3,3-hexamethyldisilazide In tetrahydrofuran at -78℃; Inert atmosphere; Stage #2: methyl iodide In tetrahydrofuran at -78 - 20℃; Inert atmosphere; |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0 °C 1.2: 0 - 20 °C 2.1: potassium hydroxide / ethanol / 48 h / 110 °C | ||
| Multi-step reaction with 2 steps 1: tetrabutylammomium bromide; potassium hydroxide / water; toluene / 3 h / 70 - 100 °C 2: sodium hydroxide; water / butan-1-ol / 14 h / 120 °C | ||
| Multi-step reaction with 2 steps 1: potassium hydroxide; tetrabutylammomium bromide / water; toluene / 3 h / 100 °C 2: water; sodium hydroxide / butan-1-ol / 4 h / 120 °C |
| Multi-step reaction with 2 steps 1: potassium hydroxide / dimethyl sulfoxide / 0 - 20 °C 2: potassium hydroxide / ethylene glycol / Reflux | ||
| Multi-step reaction with 2 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.33 h / 0 °C 1.2: 1 h / 0 - 20 °C 2.1: hydrogenchloride / water; ethylene glycol 2.2: 20 °C | ||
| Multi-step reaction with 2 steps 1: potassium hydroxide / dimethyl sulfoxide / 12 h / 20 °C 2: potassium hydroxide / ethylene glycol; water / 24 h / 100 °C | ||
| Multi-step reaction with 2 steps 1.1: sodium hydride / 1 h / 0 °C 1.2: 0 - 20 °C 2.1: water; sulfuric acid / 100 °C | ||
| Multi-step reaction with 2 steps 1.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h 1.2: 12 h 2.1: potassium hydroxide / 1,2-dimethoxyethane / 24 h / 180 °C |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1: Isobutyramide / 50 °C 2: hydrazine monohydrobromide / ethanol; water / 3 h / 80 °C | ||
| Multi-step reaction with 2 steps 1: sodium methylate / methanol / 18 h / 20 °C 2: hydrazine hydrochloride / ethanol; water / 75 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1: hydrogenchloride / water / 2 h / 65 - 70 °C / Inert atmosphere 2: Oxone; iodobenzene / water; methanol / 7 h / 40 °C / Inert atmosphere |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 64% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate In 1,4-dioxane; water at 120℃; for 0.333333h; Inert atmosphere; Microwave irradiation; | 17.a a) 2-(4-(quinolin-7-yl)phenyl)acetonitrile A solution of 2-(4-bromophenyl)acetonitrile (2.55 mmol) in 1,4-dioxane (5 mL) was treated with 7-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)quinoline (2.64 mmol), PdCl2(dppf)-CH2Cl2 adduct (0.083 mmol), and 2M aq potassium carbonate (5.10 mmol). The reaction vessel was purged with nitrogen and sealed, and the mixture irradiated in a Biotage Initiator Microwave at 120 °C for 20 min. The resulting black mixture was diluted with water (100 mL) and extracted three times with dichloromethane. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. Purification of the residue by silica gel chromatography (0-100% ethyl acetate/hexanes) afforded the title compound as a yellow solid (424 mg, 64%). MS(ES)+ m/e 245.3 [M+H]+. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 5 steps 1.1: tetrabutylammomium bromide; potassium hydroxide / water; toluene / 65 °C 2.1: potassium hydroxide / ethylene glycol / 6 h / 160 °C 2.2: pH 3 - 4 3.1: sulfuric acid / 4 h / 65 °C 4.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane / 90 °C / Inert atmosphere 5.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate / tetrahydrofuran; water / Reflux; Inert atmosphere |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 80.1% | With sodium hydride In toluene for 10h; Inert atmosphere; Reflux; | 2-(4-Bromophenyl)-3,3-bis[4-(diphenylamino)phenyl]acrylonitrile (2a). Compound 1a (2.0 g, 3.9 mmol), 60% NaH (0.6 g, 15.5 mmol) were put into a three-neck flask and dissolved into 50 mL dry toluene, dropped slowly 2-(4-bromophenyl)acetonitrile (0.8 g, 3.9 mmol) in 50 mL dry toluene into the mixture over 1 h. The mixture was refluxed for 10 h under N2 atmosphere, upon cooling down to r.t., poured the mixture into water and extracted with CH2Cl2 (50 mL*3), dried the combined organic layer over anhydrous MgSO4 and concentrated using a rotary evaporator. The residue was purified by column chromatography on silica (petroleum ether/CH2Cl2=4: 1 v/v) to give a yellow solid (1.8 g). Yield: 80.1%. 1H NMR (DMSO-d6, 400 MHz, TMS) δ: 7.52 (d, J=8.6 Hz, 2H), 7.36 (dd, J=15.2, 8.0 Hz, 10H), 7.21 (m, 10H), 7.05 (d, J=8.0 Hz, 4H), 6.92 (d, J=8.8 Hz, 2H), 6.88 (d, J=8.6 Hz, 2H), 6.75 (d, J=8.8 Hz, 2H). |
| 73% | With sodium hydride In toluene for 8.7h; Reflux; Inert atmosphere; | |
| 65% | With sodium hydride In toluene for 8h; Inert atmosphere; Reflux; | 4.3.6. 2-(4-Bromophenyl)-3,3-bis(4-(diphenylamino)phenyl)acrylonitrile (I2). Compound I1 (3 g, 5.8 mmol), 60% NaH (0.92 g,23.2mmol) were put into a two-neck flask and dissolved into 50 mLdry toluene, and 2-(4-bromophenyl)acetonitrile (1.13 g, 5.8 mmol) in 50mL dry toluene solution was dropwise added into the flask under N2 atmosphere. The mixture was stirred and refluxed for 8 h, then poured into water upon cooling and extracted with CH2Cl2 (50 mLx3), the combined organic layer was washed with water and was dried over anhydrous MgSO4, concentrated using a rotary evaporator. The residue was purified by column chromatography on silica (petroleum ether/CH2Cl2 4:1 v/v) to give a yellow solid (2.45 g).Yield: 73%. 1H NMR (DMSO-d6, 400 MHz, TMS), δ: 7.53 (d, J=8.5 Hz,2H), 7.36 (dt, J=15.2, 7.8 Hz,10H), 7.21 (m,10H), 7.03 (d, J=7.8 Hz, 4H),6.92 (d, J=8.8 Hz, 2H), 6.87 (d, J=8.5 Hz, 2H), 6.75 (d, J=8.6 Hz, 2H). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1: N-benzyl-N,N,N-triethylammonium chloride; sodium hydroxide / water / 22 h / 70 - 150 °C 2: dimethylsulfide borane complex / tetrahydrofuran; dichloromethane / 4 h / 0 - 20 °C / Inert atmosphere | ||
| Multi-step reaction with 2 steps 1: N-benzyl-N,N,N-triethylammonium chloride; sodium hydroxide / water / 22 h / 70 - 150 °C 2: dimethylsulfide borane complex / tetrahydrofuran / 4 h / 0 - 20 °C / Inert atmosphere | ||
| Multi-step reaction with 4 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.25 h / 0 °C 1.2: 18 h 2.1: lithium hydroxide / water / 18 h / Reflux 3.1: sulfuric acid / 18 h / Reflux 4.1: lithium aluminium tetrahydride / tetrahydrofuran / 2 h / 0 °C |
| Multi-step reaction with 3 steps 1: sodium hydride / diethyl ether; mineral oil; dimethyl sulfoxide / 20 °C 2: water; potassium hydroxide / diethylene glycol / 4 h / 180 °C 3: lithium aluminium tetrahydride / tetrahydrofuran / 2.33 h / 0 - 20 °C | ||
| Multi-step reaction with 3 steps 1.1: sodium hydroxide; N-benzyl-N,N,N-triethylammonium chloride / water / 6 °C 2.1: sodium hydroxide; water / ethanol / 20 - 100 °C 2.2: 0 °C 3.1: isobutyl chloroformate; sodium tetrahydroborate; N-ethyl-N,N-diisopropylamine / 1,2-dimethoxethane / 0.5 h / -10 °C | ||
| Multi-step reaction with 4 steps 1.1: sodium hydride / N,N-dimethyl-formamide / 2 h / 0 - 20 °C / Inert atmosphere 2.1: barium(II) hydroxide / isopropyl alcohol / 16 h / 100 °C 3.1: thionyl chloride / 16 h / 80 °C 4.1: lithium aluminium tetrahydride / tetrahydrofuran / 2 h / 0 - 20 °C / Inert atmosphere 4.2: 0.5 h / 0 - 20 °C / Inert atmosphere |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 3 steps 1: sodium hexamethyldisilazane / Inert atmosphere; Schlenk technique 2: diisobutylaluminium hydride / Inert atmosphere; Schlenk technique 3: ferric(III) bromide / toluene / 20 h / 110 °C / Sealed tube; Schlenk technique; Inert atmosphere |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 77% | With potassium hydroxide In methanol at 20℃; for 24h; | Synthesis of compounds (3a-h); general procedure General procedure: The appropriate 1-alkyl-5-nitro-1H-indazoles 1a-e (10 mmol) andarylacetonitriles 2a-b (12 mmol) were added with stirring to a solutionof KOH (13 g, 238 mmol) in methanol (50 mL). The mixture was stirredat room temperature for 24 h. After concentration at reduced pressure,the precipitate was collected by filtration, washed with water, followedby EtOH, and then air dried to give crude 3a-h. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 76% | With Pd(2+)*2C5F9O2(1-); trifluoroacetic acid; 6-methyl-2,2'-bipyridine; In tetrahydrofuran; water; at 130℃; for 1h;Microwave irradiation; | General procedure: A 2 mL microwave vialwas charged with 6-methyl-2,2'-bipyridine (16.3 mg, 0.096 mmol), Pd(O2CCF3)2(26.6 mg, 0.08 mmol) and 500 muL THF. After stirring at room temperature for 5minutes, <strong>[123843-65-2]2,6-difluoro-4-methoxybenzoic acid</strong> (376.2 mg, 2 mmol), nitrile (1mmol), water (50 muL) and TFA (77 muL, 1 mmol) were added and the mixture heated inthe microwave for 1 hour at 130 C. Themixture was diluted with DCM (15 mL) and 0.1 M NaOH (15 mL), the phases wereseparated and extracted with DCM (2 ×15 mL), dried with Na2SO4, filtered and concentratedunder reduced pressure. Purification by flash chromatography afforded ketone 3t in the yield stated in Table 3. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 89% | With sodium hydroxide In tetrahydrofuran; ethanol at 20℃; for 12h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 91% | Stage #1: 4-Bromophenylacetonitrile In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: 2-iodo-propane In tetrahydrofuran for 1h; Inert atmosphere; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With carbon tetrabromide; oxygen In water; ethyl acetate for 20h; Irradiation; | ||
| 67 %Spectr. | With tert.-butylhydroperoxide; C56H53ClN3P2Ru(1+)*F6P(1-) In benzene at 40℃; for 18h; Inert atmosphere; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 90% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In tetrahydrofuran; water; toluene at 90℃; for 36h; Inert atmosphere; | 18 Example 18 Bromobenzeneacetonitrile (I) 0.97 g (5 mmol),1.73 g (6 mmol) of 4-boronic acid triphenylamine,Tetrakis (triphenylphosphine) palladium 0.11 g (0.1 mmol) was dissolved in a mixed solution of toluene 45 mL / tetrahydrofuran 35 mL,Aqueous sodium carbonate (2.0 M, 5 mL) was added.Under a nitrogen atmosphere,Heating to 90 reaction 36h.The reaction liquid was cooled,After evaporating the solvent under reduced pressure,Extraction with dichloromethane (60 mL x 3)The combined organic phase,Respectively, saturated aqueous sodium carbonate solution and saturated brine,Finally, dry over anhydrous magnesium sulfate.filter,The filtrate was concentrated under reduced pressure,The residue was separated by silica gel column chromatography,The eluent is a mixed solvent of petroleum ether / ethyl acetate in a volume ratio of 45/1,Collect the eluate containing the target compound,After the solvent was removed under reduced pressure and dried,1.62 g of the yellow powder triphenylamine intermediate (IV)The yield is 90%. |
| 70% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In tetrahydrofuran; toluene at 90℃; for 36h; | |
| 69.9% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In tetrahydrofuran; toluene at 90℃; for 24h; Inert atmosphere; | 2.4.2. 2-(4’-(diphenylamino)-[1,1'-biphenyl]-4-yl)acetonitrile (2) Under nitrogen atmosphere, a mixture of (4-(diphenylamino)phenyl)boronic acid (1.74 g, 6 mmol), 2-(4-bromophenyl)acetonitrile (0.98 g, 5mmol), Pd(PPh3)4 (0.065 g, 0.06 mmol), Na2CO3 (2.0 M, 3.0 mL), and toluene (50 mL)/THF (30 mL) was stirred at 90 °C for 24 h. After it was cooled to room temperature, CHCl3 (100 mL) was added to the mixture. The organic portion was separated and washed with brine before dried over anhydrous MgSO4. The solvent was evaporated off, and the solid residues were purified by column chromatography to afford 1.26 g of 2 (green powder) with a yield of 69.9%. FTIR (KBr): υ = 2949 cm-1, 2230cm-1, 1595 cm-1, 1523 cm-1, 1490 cm-1, 1080 cm-1 1H NMR (500MHz, CDCl3): δ (ppm) 7.60 (2H, d, J = 8.5 Hz, H in phenyl), 7.47 (2H, d, J = 8.5 Hz, H in phenyl), 7.40 (2H, d, J = 8.0 Hz, H in phenyl), 7.30 (4H, t, J = 7.5 Hz, H in phenyl), 7.16 (6H, d, J = 8.5 Hz, H in phenyl), 7.07 (2H, t, J = 7.5 Hz, H in phenyl), 3.80 (2H, s, H in methylene). 13C NMR(125 MHz, CDCl3): δ (ppm) 147.59, 140.59, 133.89, 129.32, 128.34, 128.25, 127.68, 127.27, 124.56, 123.71, 123.11, 117.82, 23.31. HRMS m/z: Found 361.1695 [M+H]+; molecular formula C26H21N2 requires361.1699 [M+H]+. |
| With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; toluene at 110℃; | ||
| With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; toluene at 110℃; | ||
| With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water at 90℃; Inert atmosphere; | ||
| With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In toluene Reflux; Inert atmosphere; | ||
| With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran for 10h; Reflux; |

[ 16532-79-9 ]
[ 7310-97-6 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With sodium hydroxide; In ethanol; | [00328] FIG. 33 illustrates the synthetic pathway to create DPB A-TPE. [00329] To demonstrate the potential of AIE dots for cellular and mitochondria dual targeted image-guided PDT, we synthesized a new AIEgen, DPBA-TPE (FIG. 33). 3,3'-(2,5- Dimethoxy-l,4-phenylene)bis(2-(4-bromophenyl)acrylonitrile) (5) was prepared by Knoevenagel reaction from 2,5-dimethoxybenzene-l ,4-dicarboxaldehyde (3) and bromophenylacetonitrile (4) under basic conditions. The final product was obtained with satisfactory yields by intermediate (5) and aryl amine (10) in the presence of palladium catalyst under basic conditions. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 3 steps 1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 12 h / 60 °C 2: water; sodium hydroxide / ethanol / 12 h / 20 - 85 °C 3: hydrogenchloride / 12 h / 20 °C | ||
| Multi-step reaction with 4 steps 1: sodium hydride / N,N-dimethyl-formamide / 18 h / 0 - 60 °C 2: sodium hydroxide / ethanol; water / 15 h / 15 - 80 °C 3: sulfuric acid / 18 h / 20 °C 4: hydrogenchloride / methanol; water / 16 h / 20 °C | ||
| Multi-step reaction with 3 steps 1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 12 h / 60 °C 2: water; sodium hydroxide / ethanol / 36 h / 85 °C 3: sulfuric acid / 14 h / 20 °C |
| Multi-step reaction with 4 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.25 h / 0 °C 1.2: 12 h / 60 °C 2.1: sodium hydroxide; water / ethanol / 16 h / Reflux 3.1: potassium carbonate / N,N-dimethyl-formamide / 16 h / 0 - 20 °C 4.1: hydrogenchloride / 1,4-dioxane; water / 16 h / 50 °C |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 95% | With sodium hydroxide In ethanol at 50℃; for 5h; | |
| 95% | With sodium hydroxide In ethanol at 50℃; for 5h; | 1 Example 1 Synthesis of AIE-SRS-1 Into a 100 mL round bottom flask were dissolved 4- (phenylethynyl) benzaldehyde (206 mg, 1 mmol) and 4-bromophenylacetonitrile (196 mg, 1 mmol) in 40 mL ethanol to form a mixture. Sodium hydroxide (100 mg) was added to the mixture. After stirring for 5 h at 50 , the resulting pale yellow precipitates were filtered and washed with cold ethanol. The product was dried and weighted. Yield: 95 %.1H-NMR (400 MHz, d6-DMSO) δ (ppm) 8.13 (s, 1H) , 8.00 (d, 2H, J = 8.0 Hz) , 7.74-7.71 (m, 6H) , 7.60-7.58 (m, 2H) , 7.46-7.45 (m, 3H) .13C NMR (100 MHz, d6-DMSO) δ (ppm) 142.4, 133.6, 133.0, 132.1, 131.9, 131.5, 129.5, 129.2, 128.8, 127.9, 124.4, 122.8, 121.9, 117.5, 109.8, 91.8, 89.0. MS (MALDI-TOF) : calculated for AIE-SRS-1 (C23H14BrN) : 383.0310, found: 383.0309. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 76% | With sodium methylate In ethanol for 24h; Reflux; | 2.3. Synthesis of TPEDPAN1 and TPEDPAN1 General procedure: To a well-stirred solution of 4',4''',4''''',4'''''''-(ethene-1,1,2,2-tetrayl)tetrakis(([1,1'-biphenyl]-4-carbaldehyde)) (748 mg,1 mmol) in ethanol (20 mL), phenylacetonitriles (4.5 mmol) wasadded. To this mixture, sodium methoxide (540 mg, 10 mmol) wasadded in small portions with constant stirring, and the reactionmixture was vigorously stirred for 24 h to complete the reaction,which was monitored by TLC. After cooling to room temperature,the reaction mixture was poured into ice-cold water, and theorganic layer was extracted with DCM. The solvent was removedunder vacuum, and the residue was purified by silica gel columnchromatography to obtain the solid product. |
[ 16532-79-9 ]
[ 110677-45-7 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 98% | With potassium hydroxide; In ethanol; water; acetonitrile; at 50℃; | General procedure: Ten mmol of the acetonitrile derivate and 10 mmol of N-(4-formylphenyl) carbazole are placed ina 50-mL flask, 25 mL of ethanol are added. Then the mixture is stirred for 5 min, after that, 3 dropsof an aqueous solution 10% of potassium hydroxide is added to the mixture, the reaction is stirredand heat up to 50 C, and was monitored by thin layer chromatography until was completed, then themixture is cool down to 0 C. The formation of a crystalline precipitate is observed, it is filtered andwashed using cold EtOH. The solid is recovered and purified by recrystallization process using assolvent a mixture of acetone/EtOH 40:60. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 90% | Stage #1: ethyl bromoacetate With iodine; zinc In tetrahydrofuran for 1h; Reflux; Stage #2: 4-Bromophenylacetonitrile In tetrahydrofuran for 0.5h; Reflux; | |
| 81% | Stage #1: ethyl bromoacetate With iodine; zinc In tetrahydrofuran for 1h; Reflux; Inert atmosphere; Stage #2: 4-Bromophenylacetonitrile In tetrahydrofuran for 2h; Reflux; Inert atmosphere; | Synthesis of 3-oxo esters 33 General procedure: Activated zinc (39 g, 600 mmol) and catalytic amount of iodine were suspended in anhydrous THF (250 mL) at reflux under Argon and few drops of ethyl bromoacetate were added to initiate the reaction. After 1 hour, bromophenylacetonitrile 32 (2.9 g, 15 mmol) was added followed by dropwise addition of ethyl bromoacetate (60 mmol) over 1 hour. The reaction mixture was further refluxed for 1 hour, then diluted with THF, and quenched with aqueous K2CO3. The THF layer was collected and the residue was washed with THF for three times, and the combined THF were stirred with aqueous HCl (10%, 100 mL) at room temperature for 1 hour. The mixture was concentrated under vacuo, diluted with DCM, and washed with saturated aqueous NaHCO3. The organic layer was dried over Na2SO4 and concentrated. The residue was subjected to Combiflash (EtOAc/Hexane, 5%-10%) to give desired compound. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1: potassium hydroxide; tetrabutylammomium bromide / water; toluene / 2 h / 100 °C 2: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate / 1,4-dioxane / 16 h / 90 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 74% | With dimethylamine borane; sodium t-butanolate at 80℃; for 0.583333h; Inert atmosphere; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 4 steps 1.1: sodium hydroxide; N-benzyl-N,N,N-triethylammonium chloride / water / 60 °C 2.1: sodium hydroxide; ethanol; water / 20 - 100 °C 2.2: 0 °C 3.1: triethylamine / chloroform / 2 h / -15 °C 4.1: ammonia / chloroform / 2.17 h / -15 - 20 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 62% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In water at 90℃; for 24h; Inert atmosphere; | 4 4.4 Synthesis of 2-(4'-(10H-phenoxazin-10-yl)-[1, 1'-biphenyl]-4-yl) acetonitrile (M3) In a dry nitrogen atmosphere, a mixture of M2 (0.51 g, 1.3 mmol), 4-bromophenylacetonitrile (0.38 g, 1.95 mmol), tetrakis(triphenylphosphine)palladium (0) (0.11 g, 0.10 mmol) and potassium carbonate (1.8 g, 13 mmol) in 25 ml H2O/toluene (2/3 v/v) mixture solvent was heated under 90 °C for 24 h. After the reaction, the mixture was cooled to room temperature and quenched with water and extracted with chloroform. The combined organic layer was washed with distilled water three times and dried over anhydrous magnesium sulfate. Then the solvent was evaporated in a vacuum. The crude product was purified by column chromatography on silica gel using petroleum ether/dichloromethane (2/5 v/v) as the eluent to obtain the product as orange solid (0.30 g, 62%). 1H NMR (500 MHz, CDCl3) δ (TMS, ppm) 7.81 (d, J = 8.4 Hz, 2H), 7.69 (d, J = 8.3 Hz, 2H), 7.47 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 8.4 Hz, 2H), 6.58-6.75 (m, 6H), 6.01 (d, J = 7.9 Hz, 2H), 3.85 (s, 2H, vinyl-H). MS (ESI) (mass m/z): 375.2 [M+H]+ C26H18N2O calc. 374.3. |
| 53% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In water; toluene at 90℃; for 24h; Inert atmosphere; | (3) Under the protection of nitrogen, Will VI-b (0.5g, 1.3mmol), 4-bromophenylacetonitrile (0.38 g, 1.95 mmol), Tetrakis(triphenylphosphine)palladium (0.11 g, 0.10 mmol) And potassium carbonate (1.8g, 13mmol) Dissolved in a water/toluene volume ratio of 2:3 in a mixed solvent (25 ml), The system was warmed to reflux at 90 ° C for 24 hours. After the system is cooled, it is extracted with deionized water and dichloromethane. The obtained organic phase was dried over anhydrous MgSO 4 and dried. Concentrated under reduced pressure, Separation and purification by column chromatography, The stationary phase is 300-400 mesh silica gel. The mobile phase is dichloromethane/petroleum ether (2.5:1 by volume), Finally, an orange solid intermediate product VI-c 0.26g was obtained. The yield was 53%. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 75% | With sodium hydroxide In ethanol at 20℃; for 3h; | |
| 70% | With potassium <i>tert</i>-butylate In ethanol for 4h; Reflux; | 2.2 (2) Synthesis of intermediate TPEA: The intermediate TPE-CHO (500 mg, 1.39 mmol), 4-bromophenylacetonitrile (326.33 mg, 1.66 mmol), potassium tert-butoxide (311.31 mg, 2.77 mmol) and 20 mL of ethanol (EtOH) were added to a 100 mL round-bottom flask and the reaction was refluxed for 4 h. The color changed to yellow and solid precipitated. After the reaction was stopped, the mixture was cooled to room temperature and the product was filtered. The crude product was purified by chromatography [eluent: V (petroleum ether): V (dichloromethane) = 2:1] to obtain a yellow-green solid with a yield of 70%. |
| 70% | With potassium <i>tert</i>-butylate In ethanol at 80℃; for 3h; | 1.2 In a 100 mL round-bottom flask, TPE-CHO (800 mg, 2.22 mmol) obtained in step (1), 4-bromobenzeneacetonitrile (522 mg, 2.66 mmol), potassium tert-butoxide (498 mg, 4.44 mmol) and 20 mL of ethanol were added to react at 80° C. and refluxed for 3 h. After the reaction, solids were precipitated, which were filtered while hot and washed with ethanol to obtain a crude product, which was then subjected to column chromatography [eluent: V (petroleum ether)/V (dichloromethane) = 2:1] to obtain about 0.84 g of a yellow-green solid with a yield of 70%. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 61% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In ethanol; toluene at 90℃; for 24h; Inert atmosphere; | 1 Example 1 Under the protection of nitrogen, Take 1 part of 400 mg (2.04 mmol) of 2-(4-bromophenyl)acetonitrile, 1.2 parts of 700 mg (2.44 mmol) of 9H-carbazole-9-(4-phenyl)boronic acid, 2.3 parts 500mg (4.71mmol) sodium carbonate and 0.02 parts of 40 mg (0.035 mmol) of tetrakis(triphenylphosphine) are mixed in 10 mL of toluene and 3 mL of ethanol solution. The temperature was heated to 90 ° C and stirred and refluxed for 24 h overnight. After cooling at room temperature, the resultant was conditioned with 50 mL of water. It was extracted three times with 100 mL of dichloromethane and washed again with saturated brine. The organic extract was subjected to rotary evaporation by drying over anhydrous MgSO4. The residue was purified by column chromatography. Using dichloromethane/n-hexane (V dichloromethane: V-hexane = 1:1) the mixture was used as an eluent to obtain 450 mg of a pale white powder of 4-(4-benzoxazole) phenylacetonitrile (1). The yield was 61%. |
| 61% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In ethanol; water; toluene at 90℃; for 24h; Inert atmosphere; | 1 Example 1 Preparation of (4-(carbazol-9-yl)-1,1'-biphenyl-4'-yl)acetonitrile Under the protection of nitrogen, add p-benzocarbazole borate and p-(bromophenyl)acetonitrile (molar ratio of 1:(13)), potassium carbonate, and tetrakis(triphenylphosphine)palladium into a double-necked flask, Then add 10-20mL of toluene, ethanol and water, stir vigorously, keep the temperature at 90°C, reflux for 24h, cool to room temperature, extract, wash and filter to obtain the initial product, which is separated by chromatography column or recrystallized to obtain (4-(carbazol-9-yl)-1,1'-biphenyl-4'-yl)acetonitrile has a molecular structure shown in formula (1) in 1a, and its synthetic route is shown in formula (1), and its yield is about 61%. |
| 61% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In ethanol; toluene Reflux; Inert atmosphere; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 75% | With trimethylamine-borane; 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine; potassium <i>tert</i>-butylate In 1,2-dimethoxyethane at 120℃; for 16h; Sealed tube; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 74% | With potassium <i>tert</i>-butylate; C38H42Ir2N4O2 In neat (no solvent) at 120℃; for 2h; Inert atmosphere; Glovebox; | |
| 61 % | With potassium <i>tert</i>-butylate; C36H26Cl2N6Ni In toluene at 150℃; Glovebox; Inert atmosphere; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 70% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In ethanol; water; toluene at 90℃; for 24h; Inert atmosphere; | 4 Example 4: The reaction process of an organic small molecule semiconductor material (2Fc-Py-2CN) with piezoelectric properties containing ferrocene units is shown in the following formulas (5) and (6). Under the protection of nitrogen, add 1 part of pyrene-27-diborate pinacol ester into a two-neck flask, and add 4-bromobenzene acetonitrile (pyrene-27-diborate pinacol ester: 4-bromobenzene acetonitrile ratio 1:110), Tetratriphenylphosphine palladium (the molar ratio of tetratriphenylphosphine palladium: pyrene-27-diboric acid pinacol ester is 1:110), potassium carbonate (potassium carbonate: pyrene-27-diboric acid pinacol The molar ratio of the ester is 110) separately added into a two-necked bottle, Dissolve in a mixed solution of water, ethanol and toluene (10-20mL), stir vigorously at 90°C for 24h, After the reaction, it was extracted and washed three times with dichloromethane, and once with saturated brine. After rotary evaporation, chromatographic column separation is performed to obtain the target product 2,7-bis(4-acetonitrilephenyl)pyrene (Py-2CN), with a yield of about 40-70%. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 89% | With caesium carbonate at 125℃; for 12h; Inert atmosphere; Schlenk technique; | |
| 89% | With potassium carbonate; C25H28ClN3Ru at 120℃; for 18h; Inert atmosphere; Sealed tube; | |
| With Re(CO)5Cl; caesium carbonate; 1,1,1-tris(diphenylphosphanomethyl)ethane at 140℃; for 24h; Inert atmosphere; Sealed tube; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1: PPA / 24 h / 160 °C 2: triethylamine; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 16 h / 3800.26 Torr / Heating |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 3 steps 1.1: lithium diisopropyl amide / tetrahydrofuran / 0.5 h / -65 °C 1.2: 1 h / -65 °C 2.1: N-benzyl-N,N,N-triethylammonium chloride; potassium carbonate / acetonitrile / 6 h / 75 °C 3.1: acetic acid; sulfuric acid / 3 h / 120 °C | ||
| Multi-step reaction with 3 steps 1.1: lithium diisopropyl amide / tetrahydrofuran / 0.5 h / -65 °C 1.2: 1 h / -65 °C 2.1: N-benzyl-N,N,N-triethylammonium chloride; potassium carbonate / acetonitrile / 6 h / 75 °C 3.1: acetic acid; sulfuric acid / 3 h / 120 °C | ||
| Multi-step reaction with 2 steps 1.1: lithium diisopropyl amide / tetrahydrofuran / 1 h / -70 °C 1.2: 3.5 h / -70 - 25 °C 2.1: acetic acid; sulfuric acid / 2 h / 90 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 5 steps 1.1: lithium diisopropyl amide / tetrahydrofuran / 0.5 h / -65 °C 1.2: 1 h / -65 °C 2.1: N-benzyl-N,N,N-triethylammonium chloride; potassium carbonate / acetonitrile / 6 h / 75 °C 3.1: acetic acid; sulfuric acid / 3 h / 120 °C 4.1: caesium carbonate; RuPhos Pd G3 / N,N-dimethyl-formamide / 24 h / 100 °C / Inert atmosphere 5.1: hydrogenchloride / ethyl acetate / 12 h / 20 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 0 °C / Inert atmosphere 1.2: 1 h / 20 °C / Inert atmosphere 2.1: borane-THF / tetrahydrofuran / 4 h / 0 - 70 °C / Inert atmosphere |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 17 h / 60 °C / Cooling with ice 2: hydrogenchloride / water; acetone / 3 h / 60 °C | ||
| Multi-step reaction with 2 steps 1.1: sodium hydride / N,N-dimethyl-formamide / 30 min / Cooling with ice 1.2: 16 h / 60 °C 2.1: sulfuric acid / water; acetone / 12 h / Reflux | ||
| Multi-step reaction with 2 steps 1.1: sodium hydride / N,N-dimethyl-formamide / 10 min / 0 °C 1.2: 18 h / 60 °C 2.1: hydrogenchloride / 1,4-dioxane; water / 3 h / 85 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 75 % | Stage #1: chloroform; 4-Bromophenylacetonitrile With QPhosPd(crotyl)Cl; water; lithium hydroxide at 60℃; Stage #2: In water Acidic conditions; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 5 steps 1: sodium hydroxide; tetrabutylammomium bromide / water; toluene / 24 h / 20 °C 2: diisobutylaluminium hydride / 1 h / 0 °C 3: diethylamino-sulfur trifluoride / dichloromethane / 20 °C 4: dmap; bis(η3-allyl-μ-chloropalladium(II)); BINAP / 1,3,5-trimethyl-benzene / 120 °C / Inert atmosphere 5: sodium hydroxide; water / methanol / 1 h / 20 °C | ||
| Multi-step reaction with 5 steps 1: sodium hydroxide; tetrabutylammomium bromide / water; toluene / 24 h / 20 °C 2: diisobutylaluminium hydride / tetrahydrofuran / 1 h / 0 °C 3: diethylamino-sulfur trifluoride / dichloromethane / 20 °C 4: 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; dmap; bis(η3-allyl-μ-chloropalladium(II)) / 1,3,5-trimethyl-benzene / 120 °C 5: sodium hydroxide; water / methanol / 1 h / 20 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 3 steps 1: sodium hydride / N,N-dimethyl-formamide / 1.5 h / 0 - 65 °C 2: potassium hydroxide; dihydrogen peroxide / dimethyl sulfoxide / 1 h / 20 - 30 °C 3: potassium hydroxide; 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione / water; acetonitrile / 1 h / 20 - 30 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 3 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 1 h / 0 °C 1.2: 0 - 20 °C 2.1: water; sulfuric acid / 100 °C 3.1: triethylamine; diphenyl phosphoryl azide / toluene / 2 h / 90 °C / Inert atmosphere 3.2: 5 h / 100 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 48 % | With PdCl(C3H5)(dppb); potassium acetate In N,N-dimethyl acetamide at 120℃; Schlenk technique; Inert atmosphere; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 98.4% | With tetrabutylammonium acetate In toluene Inert atmosphere; | 233 At 20-25°C, toluene (50.0 mL) was added to a 250 mL three-necked flask. Compound A149-1 was added to the reaction flask. (Bu4N)Ac (11.5 g, 38.2 mmol, 11.6 mL, 1.50 equiv) was added to the reaction flask. Nitrogen was replaced three times. At 20-25°C, TMSN3 (5.88 g, 51.0 mmol, 6.71 mL, 2.00 equiv) was added to the reaction flask under a nitrogen atmosphere. Stir for 0.5 hours at 20-25°C. Heat to 105°C and stir for 4 hours. LCMS showed that compound A149-1 was completely reacted and the target product was detected. The reaction solution was cooled to 20-25°C. Pour into 200 mL of ice water under a nitrogen atmosphere. Extract with ethyl acetate three times, collect the organic phase, wash the organic phase three times with 300 mL of brine, dry over anhydrous sodium sulfate and filter, and concentrate in vacuo at 35°C to obtain compound A149-2 (6.11 g, 25.1 mmol, |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 74% | With potassium hydroxide In methanol at 70℃; for 7h; | 2.2.5.Synthesis of (Z)2-(4-bromophenyl)3-(4-((hydroxymethyl) (methyl)amino)phenyl)acrylonitrile (4) The reaction was conducted as mentioned in the general procedure using 4-bromophenylacetonitrile (B4, 383 mg, 1.96 mmol) and 4-((2- hydroxyethyl)(methyl)amino)benzaldehyde (A, 350 mg, 1.96 mmol), and KOH (110mg, 1.96 mmol), in methanol 10 mL. The reaction mixture was constantly stirred at 70 C for about 7 h. The compound 4 (515 mg,74 %) was obtained as a yellow crystalline solid. M.p. 109-110 C. FT-IR (KBr, cm1): 3324, 3029, 2908, 2208, 1578, 1524, 1487, 1388, 1354, 1191, 1065, 817, 718, and 520; 1H NMR; (500 MHz, CDCl3, δ, ppm):1.75 (bs, 1H, OH), 3.12 (s, 3H, N-CH3), 3.61(t, J=6 Hz, 2H, N-CH2), 3.88(t, J=6 Hz, 2H, O-CH2), 6.78 (d, J=9 Hz, 2H, ArCH), 7.39 (s, 1H, HC--C), 7.49-7.55,(m, 4H, ArCH) and 7.86 (d, J=7 Hz, 2H, ArCH). 13C NMR; (125 MHz, CDCl3, δ, ppm): 39.1, 54.4, 60.3, 103.6, 110.6, 111.8, 119.1, 121.7, 122.0, 127.0, 131.5, 132.0, 142.7, 151.2. MS (EI), m/z: [M+] calcd. for C18H17BrN2O, 357.25; found 358. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 83% | With potassium <i>tert</i>-butylate In ethanol for 6h; Reflux; | 3.2 (2) Compound C (2.21 g, 5.0 mmol) and p-bromophenylacetonitrile (980 mg, 5.0 mmol) were added to a round-bottom flask, dissolved in 20 mL of anhydrous ethanol, followed by the addition of potassium tert-butoxide (672 mg, 6.0 mmol). The mixture was stirred and refluxed for 6 h. The reaction was monitored by thin-layer chromatography (TLC). Once the reaction was complete, the system was cooled to room temperature and filtered to obtain 2.58 g of yellow-green solid compound B, with a yield of 83%. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 784 mg | With tetra(n-butyl)ammonium hydroxide In ethanol for 8h; Reflux; | 3.2 Preparation of intermediate AnCN-Br: The An-CHO (2 mmol, 772 mg) obtained in and 4-bromophenylacetonitrile (5 mmol, 970 mg) were dissolved in anhydrous ethanol. 100 μL of tetrabutylammonium hydroxide (TBAH) was added to the above solution, and the reaction was carried out under reflux for 8 hours. After the reaction was completed, the precipitate was collected and washed three times with ethanol to obtain a yellow product AnCN-Br (784 mg). Due to the poor solubility of AnCN-Br, it was directly used in the next step of the reaction. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 879 mg | With tetra(n-butyl)ammonium hydroxide In ethanol for 8h; Reflux; | 4.2-5.2 Preparation of intermediate product BZCN-Br: BZ-CHO (2 mmol, 688 mg) obtained from step and 4-bromobenzonitrile (5 mmol, 970 mg) were dissolved in anhydrous ethanol. 100 μL of tetrabutylammonium hydroxide (TBAH) was added to the solution, and the reaction was carried out under reflux for 8 hours. After the reaction was complete, the precipitate was collected and washed three times with ethanol to obtain the yellow BZCN-Br product (879 mg). |
Tags: 16532-79-9 | 4-Bromophenylacetonitrile | Aryls | Bromides | Nitriles | Benzene Compounds | Rigid Linkers | Organic Building Blocks | Bifunctional Linkers

A129155 [215800-05-8]
2-(4-Bromo-2-methylphenyl)acetonitrile
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A171809 [57775-08-3]
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A129155 [215800-05-8]
2-(4-Bromo-2-methylphenyl)acetonitrile
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A171809 [57775-08-3]
3-(4-Bromophenyl)propanenitrile
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2-(4-Bromophenyl)propanenitrile
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| H312 | Harmful in contact with skin |
| H313 | May be harmful in contact with skin |
| H314 | Causes severe skin burns and eye damage |
| H315 | Causes skin irritation |
| H316 | Causes mild skin irritation |
| H317 | May cause an allergic skin reaction |
| H318 | Causes serious eye damage |
| H319 | Causes serious eye irritation |
| H320 | Causes eye irritation |
| H330 | Fatal if inhaled |
| H331 | Toxic if inhaled |
| H332 | Harmful if inhaled |
| H333 | May be harmful if inhaled |
| H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
| H335 | May cause respiratory irritation |
| H336 | May cause drowsiness or dizziness |
| H340 | May cause genetic defects |
| H341 | Suspected of causing genetic defects |
| H350 | May cause cancer |
| H351 | Suspected of causing cancer |
| H360 | May damage fertility or the unborn child |
| H361 | Suspected of damaging fertility or the unborn child |
| H361d | Suspected of damaging the unborn child |
| H362 | May cause harm to breast-fed children |
| H370 | Causes damage to organs |
| H371 | May cause damage to organs |
| H372 | Causes damage to organs through prolonged or repeated exposure |
| H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
| Code | Phrase |
| H400 | Very toxic to aquatic life |
| H401 | Toxic to aquatic life |
| H402 | Harmful to aquatic life |
| H410 | Very toxic to aquatic life with long-lasting effects |
| H411 | Toxic to aquatic life with long-lasting effects |
| H412 | Harmful to aquatic life with long-lasting effects |
| H413 | May cause long-lasting harmful effects to aquatic life |
| H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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