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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 3096-81-9 |
Formula : | C13H9NO |
M.W : | 195.22 |
SMILES Code : | N#CC1=CC=C(OC2=CC=CC=C2)C=C1 |
MDL No. : | MFCD00017346 |
InChI Key : | UYHCIOZMFCLUDP-UHFFFAOYSA-N |
Pubchem ID : | 137821 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H302+H312+H332 |
Precautionary Statements: | P280 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLE 8 Reaction of potassium phenate with para-chlorobenzonitrile, in order to prepare para-phenoxybenzonitrile having the formula: STR22 in the presence of tris-(3,6,9-trioxadecyl)-amine in o-dichlorobenzene. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | In N,N-dimethyl-formamide; for 12h;Alkaline conditions; Reflux; Inert atmosphere; | General procedure: To a round bottom flask containing DMF the appropriate phenolanalogue (1.5 equiv.), sodium bicarbonate (5.0 equiv.) and 4-fluorobenzonitrile(1.0 equiv.) were added and refluxed under nitrogen gas for 12h. After, the resulting solution was partitioned between EtOAc and LiBraqueous solution. Using additional EtOAc, the aqueous LiBr solution waswashed three times and the combined organic layers were dried overNa2SO4, filtered, and concentrated via vacuum. The resulting concentratewas purified by silica gel chromatography.4.2.5.1. 4-phenoxybenzonitrile (14a). White solid, yield 80%. 1H NMR(400 MHz, CDCl3) δ: 7.57 (d, J = 9.0 Hz, 2H), 7.40 (dd, J = 8.5, 7.6 Hz,2H), 7.22 (t, J = 7.4 Hz, 1H), 7.06 (dd, J = 8.6, 1.1 Hz, 2H), 6.99 (d, J =9.0 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ: 161.6, 154.7, 134.1, 130.2,125.1, 120.4, 118.8, 117.9, 105.7. HRMS (ESI + ): calcd for C13H10NO[M + H]+ 196.0757, found: 196.0744. |
37% | With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 16h; | To a stirred solution 4-fluorobenzonitrile (1 g, 16.5 mmol, 1.0 eq.) and phenol (1.7 g, 18.18 mmol, 1.1 eq.) in DMF (20 mL) was added K2CO3 (6.8 g, 49.5 mmol, 3 eq.) The resulting mixture heated at 100 C. for 16 h. Following this, reaction was allowed to cool to RT and filtered through celite pad, the celite pad washed with ethyl acetate and water. The aqueous layer was separated extracted using ethyl acetate (3*30 mL). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na2SO4, filtered and concentrated under vacuum to get the solid residue. The crude was purified by normal phase silica-gel column provided title compound (1.2 g, 37%). LCMS: 196.1 [M+1]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With sodium hydroxide; In neat (no solvent); at 90℃; for 7h;Green chemistry; | General procedure: A round bottom glass tube was charged by phenol (1mmol,0.094g), iodobenzene (1mmol, 0.203g), NaOH (3mmol,0.12g), and Fe3O4AMCA-MIL53(Al)-NH2-CoII NPs(VI)(1.08mol%, 0.04g). The reaction mixture was stirred at 90C under solvent free conditions. Thin layer chromatography(TLC) or gas chromatography (GC) were used to monitor the progress of the reaction. After completion of the reaction (6h), the reaction mixture was quenched by additionof 2mL ethyl acetate. The nanostructured catalyst was separated using an external magnetic field, washed with ethanol and water before drying in an oven at 50C overnight for the next run use. The obtained crude product was purified by thin layer chromatography using n-hexane/ethyl acetate(50:1) to aford the pure diphenyl ether (0.161g, 95% yield). |
91% | With tripotassium phosphate tribasic; In N,N-dimethyl-formamide; at 80℃; for 4h; | General procedure: The catalytic efficiency of Pd0(at)magnetic PAN/AP was investigated in the Ullmann Cross-coupling reaction. Briefly, 1 mmol of aryl halides, 1 mmol of phenols, 2 mmol of tripotassium phosphate and catalyst (5 mol%) in solvent (2 ml) were added into a roundbottom flask at 80 C. The progress of the reactions was monitored by thin-layer chromatography (TLC) (EtOAc/n-Hexane, 1:10) and after their completion; the catalyst was isolated by an external magnet, washed with methanol and dried under a vacuum oven at 60 C for 12 h for next runs. On the other hand, the mixtures were worked up, purified by plate chromatography and prepared for1HNMR and 13CNMR analysis. |
89% | With C15H16BrCl2NPdSe; potassium carbonate; In dimethyl sulfoxide; at 110℃; | General procedure: An oven-dried10 mL pressure tube was charged with aryl bromide (1.0 mmol),phenol (1.2 mmol), K2CO3 (2.5.0 mmol), DMSO (3.0 mL), and catalyst (5 or 6). The reaction mixture was stirred and heated at 110 C in open air conditions for 16 h. Thereafter reaction mixture was cooled to room temperature and 25 mL of distilled water was added. The resulting mixture was extracted with ethyl acetate(2 25 mL). The organic layer was washed with water(2 x 25 mL) and dried over anhydrous Na2SO4. The solvent of theextract was removed with rotary evaporator and the resulting residuewas purified by column chromatography on silica 60 (1 x 12 cm) using ethyl acetate and hexane mixture as eluent. Pure products were authenticated by 1H NMR and their data are presented in the supporting information. |
87% | With copper(II) oxide; potassium hydroxide; In N,N-dimethyl acetamide; at 27℃; for 24h;Inert atmosphere; Sealed tube; | General procedure: A magnetic stirring bar, nanocrystalline CuO (10 mg, 3 mol %), KOH (112 mg, 2 mmol) and phenol/substituted phenol/ thiophenol (1.2 mmol) were added into an oven-dried flask (25 mL). The flask was sealed with a septum, followed by three cycles of evacuation and filling with dry nitrogen. Then aryl halide (1 mmol) and N,N-dimethyl acetamide (DMAc) (4 mL) were injected through a syringe. The flask was sealed and stirred under nitrogen until the completion of the reaction (as monitored by TLC or GC). The catalyst was recovered from the reaction mixture and washed several times with ethyl acetate. The catalyst-free reaction mixture was quenched with brine solution and the product was extracted with ethyl acetate. The combined organic extracts were dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated and the residue was purified by column chromatography on silica gel (hexane/ethyl acetate, 80/20) to afford the product with high purity. |
86% | With tetrabutylammonium bromide; Cs2CO3; In dimethyl sulfoxide; at 120℃; for 12h; | General procedure: Polymer supported Cu(II) catalyst (0.05 g, 0.0098 mmol) in DMSO (5 mL) was taken in a 100 ml R.B flask and stirred at room temperature for 10 min. Then aryl halide (1 mmol), phenol(1 mmol), tetrabutylammonium bromide (tBu4NBr) (0.1 mmol),Cs2CO3 (1 mmol) and DMSO (5 mL) were added to it. The final reaction mixture was refluxed at 120 C under an open air condition.The reaction mixtures were collected at different time intervals and identified by GCMS and quantified by GC. After the completion of the reaction, the catalyst was filtered off and washed with water followed by acetone and dried in oven. The filtrate was extracted with ethyl acetate (3 x 20 ml) and the combined organic layers were dried with anhydrous Na2SO4 by vacuum. The filtrate was concentrated by vacuum and the resulting residue was purified by column chromatography on silica gel to provide the desired product. |
86% | With thio-xanthene-9-one; (2,2'-bipyridine)nickel(II) dibromide; N-tert-butylisopropylamine; In acetonitrile; for 72h;Inert atmosphere; Irradiation; Green chemistry; | p-bromobenzonitrile (0.2 mmol), phenol (0.6 mmol), TXO (20 mol %), Ni(bpy)Br2 (10 mol %), t-BuNH(i-Pr) (0.4 mmol) and MeCN ( 3 mL) was added to a dry reaction tube with a magnetic stirrer, then the reaction tube was replaced with N2 3 times, and the reaction was stirred for 72 hours under 45 W CFL irradiation. After the reaction, 5 mL of water was added, then extracted with 3 × 5 mL of ethyl acetate, the organic phases were combined, and the organic phases were dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated by rotary evaporation and separated by silica gel column chromatography. The target product was obtained (yield 86%). |
76% | With [NiII(N-((6-fluoropyridin-2-yl)methyl)(pyridin-2-yl)-N-(pyridin-2-ylmethyl)methanamine)(acetate)(H2O)][BPh4]; potassium carbonate; In dimethyl sulfoxide; at 120℃; for 10h;Catalytic behavior; | General procedure: In a round bottom flask, mixture of phenol (1.2 mmol), aryl halides(1 mmol) and K2CO3 (2 mmol) have been taken in 5 mL DMSO. Thecomplexes (1-3) (4 mol%) were then added into the reaction mixture.Thereafter, the reaction mixture was heated at 120 C for the given time.The progress of reaction was monitored through TLC made of silica andafter the maximum conversion reached, reactions were quenched bywater after cooling and extracted using ethyl acetate. Then, it was driedover anhydrous sodium sulphate and subjected to GC analysis usingShimadzu GC-2014. The products were detected and quantified by GC(FID) with the following temperature program: injector temperature240 C; initial temperature 50 C, isothermal for 3 min then heating rate10 C min 1 to 200 C and thereafter another isothermal of 3 min; FIDtemperature 250 C. |
74% | With potassium-t-butoxide; In dimethyl sulfoxide; at 120℃; for 2h;Inert atmosphere; | General procedure: A 25-mL Schlenk tube was flame-dried under vacuum and filled with argon after cooling to room temperature. To this tube were added phenol (1.0 mmol), t-BuOK (2.0 mmol). The tube was then evacuated and backfilled with argon (3 cycles). A dry DMSO solution (1.0 mL) of aryl bromides(2.0 mmol) was loaded into a plastic syringe. After the tube was purged with argon, this solutionwas injected into bottom of the tube using a long needle syringe. The mixture was stirred under Ar atmosphere in sealed Schlenk tubes at the corresponding temperature. When the reaction was cooled down to room temperature, the mixture was filtered through a short plug of silica gel and washed with 100 mL dichloromethane and water. The combined organic phase was concentrated under vacuum. The product was purified through flash column chromatography on 200-300 mesh silica gel with petroleum ether/ethyl acetate as eluent with a suitable ratio according to the TLC experiments. The identity and purity of the product were ascertained by GC-MS, HRMS, 1H and 13C NMR spectroscopy. |
70% | With tetrabutylammonium bromide; Cs2CO3; In dimethyl sulfoxide; at 120℃; for 12h; | General procedure: Cu- catalyst (0.05 g) in DMSO (5 mL) was taken in a 100 mLround bottom flask and stirred at room temperature for 10 min.Then aryl halide (1 mmol), phenol (1 mmol), tetrabutylammoniumbromide (tBu4NBr) (0.1 mmol), Cs2CO3(1 mmol) and DMSO (5 mL)were added to it. The final reaction mixture was heated at 120Cunder an open air condition. The reaction mixtures were collectedat different time intervals and identified by GC-MS and quantifiedby GC. After the completion of the reaction, the catalyst was fil-tered off and washed with water followed by acetone and dried inoven. The filtrate was extracted with ethyl acetate (3 × 20 mL) andthe combined organic layers were dried with anhydrous Na2SO4byvacuum. The filtrate was concentrated by vacuum and the result-ing residue was purified by column chromatography on silica gelto provide the desired product. |
70% | With copper (I) iodide; 2-(2-benzoylhydrazine-1-carbonyl)-1-benzylpyrrolidine 1-oxide; Cs2CO3; In acetonitrile; at 80℃; for 12h;Inert atmosphere; Sealed tube; | General procedure: CuI (19.2 mg, 0.1 mmol, 10 mol%), Cs2CO3 (650 mg, 2.0 mmol) and L2 (34 mg, 0.1 mmol, 10 mol%) were added to a re-sealable 25 mL test tubes with Teflon septa. The tube was evacuated and backfilled three times with nitrogen. Add the corresponding solvent (EtOH or CH3CN, 1 mL) via syringe under countercurrent nitrogenflow, continue adding halides (1.5 mmol) and nucleophile (1.0 mmol), seal the test tube. The reaction mixture was heated at 80 C for 12 h, and then allowed to cool to room temperature. After the reaction mixture was diluted with CH2Cl2, the precipitate was removed by filtration and washed with water. After extraction, the organic phase was dried over anhydrous sodium sulfate and concentrated by rotary evaporation. The residue was purified by column chromatography. |
65% | With Cs2CO3; copper(II) bromide; 1,1'-azobis(1-cyanocyclohexanenitrile); In N,N-dimethyl-formamide; at 100℃; for 1.5h;Microwave irradiation; Green chemistry; | General procedure: a mixture of aryl halide (1 mmol), unsubstituted or substituted phenol (1 mmol), Cs2CO3 (1 mmol), ACHN (0.2 mmol %), CuBr (0.2 mmol %) in DMF (10 mL) were added to the microwave tube. The reaction was found to be stable to air and DMF was used directly without purification. The mixture was reacted in a microwave oven at 100 C (extern temperature) for 30-60 min and the progress of the reaction was monitored byTLC. After completion of the reaction, it was allowed to reach room temperature; 10 mL of water was added and then the crude was extracted with ethyl ether (3 15 mL). Organic layer was washed with water (2 15 mL), dried over Na2SO4 and filtered. After removal of the solvent, the diaryl ether was isolated by silica gel column chromatography. |
59% | With tris(dibenzylideneacetone)dipalladium(0) chloroform complex; di-tert-butyl(2′,4′,6′- triisopropyl-3,6-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine; Cs2CO3; In neat (no solvent); at 110℃; for 18h;Sealed tube; Inert atmosphere; | General procedure: An oven-dried screw-cap tube was cooled to roomtemperature under argon pressure and was charged with aryl halide(1.0 mmol), phenol (1.2 mmol), the ligand (2 mol%) and Pd2(dba)3·CHCl3(10 mg, 1 mol%). The mixture was well homogenized followed by additionof Cs2CO3 (650 mg, 2.0 mmol). The tube was sealed and placed in a preheatedoil bath at 110 C and stirred for 18 h. The mixture was thenallowed to cool to room temperature, and the resulting dark heterogeneousmixture was treated with water (10 ml) and ethyl acetate (10 ml). Theorganic phase was collected, filtered through a small pad of Celite andconcentrated under reduced pressure. The crude product was purifiedby flash chromatography on silica gel. |
With C25H22Cl2NPPd; potassium carbonate; In dimethyl sulfoxide;Reflux;Catalytic behavior; | General procedure: A mixture of aryl halide (1.0 mmol), phenol (1.2 mmol), potas- sium carbonate (2.0 mmol), catalyst (0.1 mol%) and 4.0 mL of dimethylsulfoxide (DMSO) was taken in an oven dried round bot- tom flask of 100 mL capacity and refluxed at 110 C. The progress of the reaction was monitored through TLC. When the stage of the maximum conversion reached, the mixture was cooled to room temperature. The mixture was extracted using ethyl acetate and washed three times with water. The organic layer was made free from water using anhydrous sodium sulphate. Finally, the solvent was evaporated to obtain the product. The conversion has been es- timated using 1 H NMR study. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With 5%-palladium/activated carbon; hydrogen; In methanol; for 3h;Inert atmosphere; | 4-Phenoxybenzonitrile (200 mg, 1.00 mmol) was dissolved in 8 mL MeOH and 5% Pd/C (0.2 equiv, 400 mg) was added. The reaction was stirred for 3 h under an H2 atmosphere and filtered through celite. Purification by pTLC with 10% MeOH, 2% Et3N in DCM afforded 4-phenoxybenzylamine as a white solid (179 mg,88%). 42 (1.1 equiv, 22 mg) was dissolved in toluene with 2,5-dimethoxyaniline (1 equiv, 8 mg), BINAP (0.3 equiv, 11 mg),Pd(OAc)2 (0.15 equiv, 2 mg) and Cs2CO3 (2.5 equiv, 46 mg) and the mixture was stirred for 15 h at 105 C. The solvent was removed and the crude product was filtered through silica, eluting with EtOAc. Final purification by pTLC with 50% EtOAc in hexane afforded 34 as colorless oil (12.4 mg, 48%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With N,N-dimethylglycine hydrochoride; caesium carbonate;copper(l) iodide; In 1,4-dioxane; at 90℃; for 88h; | To phenol (1.23 g, 13.10 mmol), copper(l) iodide (333 mg, 1.75 mmol), cesium carbonate (5.69 g, 17.47 mmol), 4-iodobenzonithle (2.00 g, 8.73 mmol) and N,N-dimethylglycine hydrochloride (366 mg, 2.62 mmol) under nitrogen was added degassed 1 ,4- dioxane (10.0 ml_). The whole mixture was heated at 90 0C for 88 hours. The cooled mixture was partitioned between ethyl acetate (100 ml_) and water (100 ml_). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (2 x 100 ml_). The organic layers were combined and washed with brine (100 ml_) and dried with Na2SO4 and concentrated in vacuo. The crude material was purified by column chromatography EtOAc/ Hex (1 :12 ? 1 :8) to give the pure product as a white solid (quantative yield). 1H NMR (300 MHz, CDCL3) d(ppm): 7.00 (2H, d, J = 9.1 Hz), 7.06 (2H, d, J = 7.6 Hz), 7.23 (1 H, t, J = 7.2 Hz), 7.41 (2H, t, J = 8.1 Hz), 7.59 (2H, d, J = 9.1 Hz). 13C NMR (75 MHz, CDCL3) d(ppm): 105.9, 118.0 (CH), 119.0, 120.5 (CH), 125.3 (CH), 130.4 (CH), 134.2 (CH), 154.9, 161.8. MS (FAB+): 196 (MH+). HRMS for Ci3H9NO (MH+): calculated: 196.0762; found 196.0780. |
100% | With caesium carbonate;copper(l) iodide; N,N-dimethylglycine hydrochoride; In 1,4-dioxane; at 90℃; for 88h;Inert atmosphere; | To phenol (1.23 g, 13.10 mmol), copper(I) iodide (333 mg, 1.75 mmol), cesium carbonate (5.69 g, 17.47 mmol), 4-iodobenzonitrile (2.00 g, 8.73 mmol) and N,N-dimethylglycine hydrochloride (366 mg, 2.62 mmol) under nitrogen was added degassed 1,4-dioxane (10.0 mL). The whole mixture was heated at 90 C. for 88 hours. The cooled mixture was partitioned between ethyl acetate (100 mL) and water (100 mL). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (2×100 mL). The organic layers were combined and washed with brine (100 mL) and dried with Na2SO4 and concentrated in vacuo. The crude material was purified by column chromatography EtOAc/Hex (1:12→1:8) to give the pure product as a white solid (quantitative yield). 1H NMR (300 MHz, CDCL3) δ(ppm): 7.00 (2H, d, J=9.1 Hz), 7.06 (2H, d, J=7.6 Hz), 7.23 (1H, t, J=7.2Hz), 7.41 (2H, t, J=8.1 Hz), 7.59 (2H, d, J=9.1 Hz). 13C NMR (75 MHz, CDCL3) δ(ppm): 105.9, 118.0 (CH), 119.0, 120.5 (CH), 125.3 (CH), 130.4 (CH), 134.2 (CH), 154.9, 161.8. MS (FAB+): 196 (MH+). HRMS for C13H9NO (MH+): calculated: 196.0762; found 196.0780. |
96% | With copper(l) iodide; potassium carbonate; dimethylbiguanide; In acetonitrile; at 20 - 60℃; for 10.1667h; | General procedure: To a 25 mL flask containing a mixture of CuI (19.2 mg,0.1 mmol), metformin (0.1 mmol), phenol (1.0 mmol), and K2CO3(2 mmol, 276 mg) in CH3CN (5 mL) was added an aryl halide(1.1 mmol). The mixture was stirred for 10 min at room temperature, and then heated to 60∘C for the appropriate amount of time(see Table 4). The progress of the reaction was monitored by TLC. After completion of the reaction, the mixture was extracted with EtOAc (5 1 mL) and the organic phase separated and evaporated. Further purification by column chromatography gave the desired coupled product. |
95% | With tetrabutylammomium bromide; caesium carbonate; In dimethyl sulfoxide; at 120℃; for 10h; | General procedure: Polymer supported Cu(II) catalyst (0.05 g, 0.0098 mmol) in DMSO (5 mL) was taken in a 100 ml R.B flask and stirred at room temperature for 10 min. Then aryl halide (1 mmol), phenol(1 mmol), tetrabutylammonium bromide (tBu4NBr) (0.1 mmol),Cs2CO3 (1 mmol) and DMSO (5 mL) were added to it. The final reaction mixture was refluxed at 120 C under an open air condition.The reaction mixtures were collected at different time intervals and identified by GCMS and quantified by GC. After the completion of the reaction, the catalyst was filtered off and washed with water followed by acetone and dried in oven. The filtrate was extracted with ethyl acetate (3 x 20 ml) and the combined organic layers were dried with anhydrous Na2SO4 by vacuum. The filtrate was concentrated by vacuum and the resulting residue was purified by column chromatography on silica gel to provide the desired product. |
95% | With copper(I) oxide; caesium carbonate; imidazole-4-carboxylic acid; In acetonitrile; at 80℃; for 24h; | General procedure: To a screw-capped vial (4-mL) were added Cs2CO3 (1.0 mmol, 325 mg), Cu2O (0.005 mmol, 0.7 mg), 1H-imidazole-4-carboxylic acid (0.01 mmol, 1.1 mg) and acetonitrile (0.25 mL). The vial was sealed with septum and allowed to stir for a while; the iodoarene (0.5 mmol) and phenol (0.6 mmol) were then injected into the reaction mixture via a syringe. The septum was removed, and the vial was sealed with a screw cap. The reaction mixture was stirred at 80 oC for 24 h. The crude reaction mixture was diluted with CH2Cl2, filtered through a thin Celite pad, and concentrated in vacuo. The residue was isolated through a column chromatography by using hexane and ethyl acetate as eluent to give the pure product. Products 3a-v were obtained according to this procedure. The known structures were characterized by the 1H NMR and 13C NMR of reported literatures.1-3 Spectral data, 1H NMR and 13C NMR spectra for all the new compounds are listed below. |
85% | With copper(l) iodide; 2-(2-benzoylhydrazine-1-carbonyl)-1-benzylpyrrolidine 1-oxide; caesium carbonate; In acetonitrile; at 80℃; for 12h;Inert atmosphere; Sealed tube; | General procedure: CuI (19.2 mg, 0.1 mmol, 10 mol%), Cs2CO3 (650 mg, 2.0 mmol) and L2 (34 mg, 0.1 mmol, 10 mol%) were added to a re-sealable 25 mL test tubes with Teflon septa. The tube was evacuated and backfilled three times with nitrogen. Add the corresponding solvent (EtOH or CH3CN, 1 mL) via syringe under countercurrent nitrogenflow, continue adding halides (1.5 mmol) and nucleophile (1.0 mmol), seal the test tube. The reaction mixture was heated at 80 C for 12 h, and then allowed to cool to room temperature. After the reaction mixture was diluted with CH2Cl2, the precipitate was removed by filtration and washed with water. After extraction, the organic phase was dried over anhydrous sodium sulfate and concentrated by rotary evaporation. The residue was purified by column chromatography. |
83% | With caesium carbonate; In dimethyl sulfoxide; at 20 - 80℃; for 10h; | The compound 4-cyanoiodobenzene 1a (0.023 g, 0.10 mmol, 1.0 eqv.) was added to the reactor in that order.DMSO (0.3 ml), Cs2CO3 (0.065 g, 0.20 mmol, 2.0 eq.).Phenol 2a (0.0113 g, 0.12 mmol, 1.2 eq.) was stirred at room temperature for 10 minutes.Then placed in an 80 C oil bath, reacted under light for 10 h,After the TLC detection reaction is completed, the reaction solution is subjected to filtration, extraction and column chromatography.The target product 3a was obtained in a yield of 83%. |
79% | With caesium carbonate; In dimethyl sulfoxide; at 20 - 80℃; for 10.1667h;Irradiation; | The compound 4-cyanoiodobenzene 1a (1.0 mmol), DMSO (5 ml), Cs2CO3 (2.0 mmol), and phenol 2a (1.2 mmol) were added to the mixture, and the mixture was stirred at room temperature for 10 minutes. Then placed in an 80 C oil bath, reacted under lightAfter 10 h, after TLC detection reaction, the reaction solution was filtered, extracted and subjected to column chromatography to obtain the target product 4a, yield 79%. |
79% | With caesium carbonate; In dimethyl sulfoxide; at 20 - 80℃; for 10.1h;Irradiation; | The compound 4-cyanoiodobenzene 1a (1.0 mmol) was added to the reactor in that order.DMSO (5 ml), Cs2CO3 (2.0 mmol), phenol 2a (1.2 mmol) was stirred at room temperature for 6 min.Then, it was placed in an oil bath at 80 C, and reacted for 10 hours under light. After the TLC detection reaction was completed, the reaction solution was subjected to filtration, extraction and column chromatography to obtain the objective product 4a, yield 79%. |
55% | With sodium hydroxide; In neat (no solvent); at 90℃; for 8h;Green chemistry; | General procedure: A round bottom glass tube was charged by phenol (1mmol,0.094g), iodobenzene (1mmol, 0.203g), NaOH (3mmol,0.12g), and Fe3O4AMCA-MIL53(Al)-NH2-CoII NPs(VI)(1.08mol%, 0.04g). The reaction mixture was stirred at 90C under solvent free conditions. Thin layer chromatography(TLC) or gas chromatography (GC) were used to monitor the progress of the reaction. After completion of the reaction (6h), the reaction mixture was quenched by additionof 2mL ethyl acetate. The nanostructured catalyst was separated using an external magnetic field, washed with ethanol and water before drying in an oven at 50C overnight for the next run use. The obtained crude product was purified by thin layer chromatography using n-hexane/ethyl acetate(50:1) to aford the pure diphenyl ether (0.161g, 95% yield). |
36% | With L-valine; cobalt(II) diacetate tetrahydrate; caesium carbonate; zinc; In acetonitrile; at 135℃; for 48h;Inert atmosphere; Green chemistry; | General procedure: An oven-dried sealed tube equipped with a magneticstirring bar was charged with aryl iodide (0.65 mmol),Co(OAc)24H2O (15 mol%), l-valine (30 mol%), cesiumcarbonate (2 equiv.), and phenol (0.78 mmol). Acetonitrilesolvent (2.5 cm3) was added and the sealed tube wasevacuated using a vacuum pump, filled with nitrogen,and tightly sealed. It was then stirred in a pre-heated oil bath for 24-48 h. After the completion of the reaction, thereaction mixture was extracted with 15 cm3 of EtOAc andthe EtOAc layer was separated and washed with water.The aqueous layer was collected and further extractedtwo more times with EtOAc (2 × 15 cm3). The combinedorganic layers were dried over anhydrous Na2SO4andevaporated using a rotatory evaporator. The residue waslater purified by column chromatography (silica 100-200mesh) using hexane-EtOAc mixture as the eluent. |
With caesium carbonate; In dimethyl sulfoxide; at 20 - 80℃; for 10.6667h; | The compound 4-cyanoiodobenzene 1a (0.023 g, 0.10 mmol, 1.0 eq.), DMSO (0.3 ml), Cs2CO3 (0.065 g 0.20 mmol, 2.0 eq.), phenol 2a (0.0113 g, 0.12 mmol, 1.2 eq., and stirred at room temperature for 40 minutes. Then, it was placed in an oil bath at 80 C, and reacted for 10 hours under light. After the TLC detection reaction was completed, the reaction solution was subjected to filtration, extraction and column chromatography to obtain the objective product 3a, yield 83%. |
Yield | Reaction Conditions | Operation in experiment |
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99% | With di-tert-butyl{2′-isopropoxy-[1,1′-binaphthalen]-2-yl}phosphane; tripotassium phosphate tribasic; Palladium(0) bis(dibenzylideneacetone); In toluene; at 110℃; for 18h;Inert atmosphere;Catalytic behavior; | General procedure: An oven-dried Schlenk tube was evacuated and backfilled with nitrogen. The Schlenk tube was charged with Pd(bda)2 (11.5 mg,0.02 mmol), L1 (13.7 mg, 0.03 mmol), K3PO4 (424.5 mg, 2 mmol), and toluene (1.0 mL). After stirring for 15 min, the solution of arylhalide (1.0 mmol) and phenol (1.2 mmol) in toluene (1.5 mL) was added. The septum was replaced with an inside reflux condenser, and then the reaction mixture was stirred for 18 h at 110 C. Then,the reaction mixture was cooled to room temperature and quenched with water (5 mL). After separating the organic phase, the aqueous phase was extracted with ethyl acetate (3 mL3), and the combined organic phase was dried over anhydrous Na2SO4. The solvent was concentrated under reduced pressure, and then the crude material was purified by column chromatography on silica gel |
92% | With copper (I) iodide; potassium carbonate; dimethylbiguanide; In acetonitrile; at 20 - 60℃; for 10.1667h; | General procedure: To a 25 mL flask containing a mixture of CuI (19.2 mg,0.1 mmol), metformin (0.1 mmol), phenol (1.0 mmol), and K2CO3(2 mmol, 276 mg) in CH3CN (5 mL) was added an aryl halide(1.1 mmol). The mixture was stirred for 10 min at room temperature, and then heated to 60∘C for the appropriate amount of time(see Table 4). The progress of the reaction was monitored by TLC. After completion of the reaction, the mixture was extracted with EtOAc (5 1 mL) and the organic phase separated and evaporated. Further purification by column chromatography gave the desired coupled product. |
81% | With copper(II) oxide; potassium hydroxide; In N,N-dimethyl acetamide; at 27℃; for 20h;Inert atmosphere; Sealed tube; | General procedure: A magnetic stirring bar, nanocrystalline CuO (10 mg, 3 mol %), KOH (112 mg, 2 mmol) and phenol/substituted phenol/ thiophenol (1.2 mmol) were added into an oven-dried flask (25 mL). The flask was sealed with a septum, followed by three cycles of evacuation and filling with dry nitrogen. Then aryl halide (1 mmol) and N,N-dimethyl acetamide (DMAc) (4 mL) were injected through a syringe. The flask was sealed and stirred under nitrogen until the completion of the reaction (as monitored by TLC or GC). The catalyst was recovered from the reaction mixture and washed several times with ethyl acetate. The catalyst-free reaction mixture was quenched with brine solution and the product was extracted with ethyl acetate. The combined organic extracts were dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated and the residue was purified by column chromatography on silica gel (hexane/ethyl acetate, 80/20) to afford the product with high purity. |
40% | With sodium hydroxide; In neat (no solvent); at 90℃; for 13h;Green chemistry; | General procedure: A round bottom glass tube was charged by phenol (1mmol,0.094g), iodobenzene (1mmol, 0.203g), NaOH (3mmol,0.12g), and Fe3O4AMCA-MIL53(Al)-NH2-CoII NPs(VI)(1.08mol%, 0.04g). The reaction mixture was stirred at 90C under solvent free conditions. Thin layer chromatography(TLC) or gas chromatography (GC) were used to monitor the progress of the reaction. After completion of the reaction (6h), the reaction mixture was quenched by additionof 2mL ethyl acetate. The nanostructured catalyst was separated using an external magnetic field, washed with ethanol and water before drying in an oven at 50C overnight for the next run use. The obtained crude product was purified by thin layer chromatography using n-hexane/ethyl acetate(50:1) to aford the pure diphenyl ether (0.161g, 95% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20% | With copper(l) iodide; potassium carbonate; dimethylbiguanide; In acetonitrile; at 20 - 60℃; for 24.1667h; | General procedure: To a 25 mL flask containing a mixture of CuI (19.2 mg,0.1 mmol), metformin (0.1 mmol), phenol (1.0 mmol), and K2CO3(2 mmol, 276 mg) in CH3CN (5 mL) was added an aryl halide(1.1 mmol). The mixture was stirred for 10 min at room temperature, and then heated to 60∘C for the appropriate amount of time(see Table 4). The progress of the reaction was monitored by TLC. After completion of the reaction, the mixture was extracted with EtOAc (5 1 mL) and the organic phase separated and evaporated. Further purification by column chromatography gave the desired coupled product. |
7% | With tetrabutylammomium bromide; caesium carbonate; In dimethyl sulfoxide; at 120℃; for 20h; | General procedure: Polymer supported Cu(II) catalyst (0.05 g, 0.0098 mmol) in DMSO (5 mL) was taken in a 100 ml R.B flask and stirred at room temperature for 10 min. Then aryl halide (1 mmol), phenol(1 mmol), tetrabutylammonium bromide (tBu4NBr) (0.1 mmol),Cs2CO3 (1 mmol) and DMSO (5 mL) were added to it. The final reaction mixture was refluxed at 120 C under an open air condition.The reaction mixtures were collected at different time intervals and identified by GCMS and quantified by GC. After the completion of the reaction, the catalyst was filtered off and washed with water followed by acetone and dried in oven. The filtrate was extracted with ethyl acetate (3 x 20 ml) and the combined organic layers were dried with anhydrous Na2SO4 by vacuum. The filtrate was concentrated by vacuum and the resulting residue was purified by column chromatography on silica gel to provide the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With caesium carbonate;silica gel; In dichloromethane; ethyl acetate; toluene; | EXAMPLE 18 Synthesis of 4-Phenoxybenzonitrile 4-Bromobenzonitrile (2.5 mmol), phenol (3.5 or 5.0 mmol), Cs2CO3 (3.5 or 5.0 mmol), (CuOTf)2 PhH (0.0625 mmol, 5.0 mol % Cu), ethyl acetate (0.125 mmol, 5.0 mol %), 1-naphthoic acid (3.5 mmol), molecular sieves (625 mg) and toluene (1.5 mL) were added to an oven-dried test tube which was then sealed with a septum, purged with argon, and heated to 110 C under argon until the aryl halide was consumed as determined by GC analysis. Upon cooling at room temperature, dichloromethane was added and the solvent was removed by filtration. The remaining molecular sieves were stirred with another portion of dichloromethane for 1 h at room temperature, and the solvent was removed by filtration. The combined organic phases were washed with 5% aqueous NaOH. The aqueous layer was then extracted three times with dichloromethane and the combined organic layers were washed with brine. The organic layer was dried over Mg2SO4 and concentrated under vacuum to give the crude product. Purification by flash column chromatography (3% EtOAc/hexane) gave the analytically pure product as a clear oil (405 mg, 86% yield). 1H NMR (300 MHz, CDCl3) δ 7.57 (d, J=8.7 Hz, 2H), 7.40 (t, J=7.9Hz, 2H), 7.22 (t, J=7.6Hz, 1H), 7.05 (d, J=7.9Hz, 2H), 6.98 (d, J=8.8 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 154.6, 133.9, 130.0, 124.9, 120.2, 118.6, 117.7, 105.6; IR (neat): 3068, 2226, 1586, 1483, 1245, 1165 cm-1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With trimethylsilylazide; di(n-butyl)tin oxide; In toluene; | A solution of <strong>[3096-81-9]4-phenoxybenzonitrile</strong> (9.87 g), dibutyltin oxide (3.88 g), and trimethylsilyl azide (33.5 ml) in anhydrous toluene (200 ml) was heated to reflux for 6 hours. The reaction mixture was washed with 1.6M sodium hydroxide (2*250 ml). The combined aqueous layer was washed with diethyl ether (4*120 ml) then acidified to pH 6 with concentrated hydrochloric acid. The acidic solution was washed with ethyl acetate (3*200 ml) and the combined organic layer was dried over anhydrous sodium sulfate, filtered and evaporated to dryness to give 5-(4-phenoxyphenyl)-1H-tetrazole as a white powder. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | REFERENCE EXAMPLE 34 4-Phenoxybenzonitrile The title compound was obtained from 4-phenoxybenzaldehyde by the method similar to that in Reference Example 32. Yield: 80%. 1H NMR (CDCl3) δ 6.97-7.19 (4H, m), 7.20-7.28 (1H, m), 7.37-7.46 (2H, m), 7.57-7.64 (2H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With hydroxylamine; In ethanol; for 3h;Heating / reflux; | In ethanol (5.0 mL), was combined <strong>[3096-81-9]4-phenoxybenzonitrile</strong> (200 mg, 1.02 mmol) and hydroxylamine (250 μL, 4.09 mmol). The mixture was refluxed for 3 hours. The reaction was cooled and then concentrated in vacuo to give the product, which was taken to the next step without further purification (quantative yield). 1H NMR (500 MHz, CDCL3) d(ppm): 4.87 (2H, bs), 7.01 (2H, d, J = 9.0 Hz), 7.03 (2H, dd, J = 8.7, 1.1 Hz), 7.15 (2H, tt, J = 7.4, 1.1 Hz), 7.36 (2H, dd, J = 8.6, 7.3 Hz), 7.59 (2H, d, J = 9.O Hz)- 13C NMR (^S MHz1 CDCL3) S(PPm): 118.6 (CH), 119.6 (CH), 124, 127.3, 127.6 (CH), 130.1 (CH), 152.5, 156.6, 159.3. MS (FAB+): 229 (MH+). HRMS for Ci3Hi2N2O2 (MH+): calculated: 229.0977; found 229.0977. |
100% | With hydroxylamine; In ethanol; for 3h;Reflux; | In ethanol (5.0 mL), was combined <strong>[3096-81-9]4-phenoxybenzonitrile</strong> (200 mg, 1.02 mmol) and hydroxylamine (250 μL, 4.09 mmol). The mixture was refluxed for 3 hours. The reaction was cooled and then concentrated in vacuo to give the product, which was taken to the next step without further purification (quantitative yield). 1H NMR (500 MHz, CDCL3) δ(ppm): 4.87 (2H, bs), 7.01 (2H, d, J=9.0 Hz), 7.03 (2H, dd, J=8.7, 1.1 Hz), 7.15 (2H, tt, J=7.4, 1.1 Hz), 7.36 (2H, dd, J=8.6, 7.3 Hz), 7.59 (2H, d, J=9.0 Hz). 13C NMR (125 MHz, CDCL3) δ(ppm): 118.6 (CH), 119.6 (CH), 124, 127.3, 127.6 (CH), 130.1 (CH), 152.5, 156.6, 159.3. MS (FAB+): 229 (MH+). HRMS for C13H12N2O2 (MH+): calculated: 229.0977; found 229.0977. |
Tags: 3096-81-9 synthesis path| 3096-81-9 SDS| 3096-81-9 COA| 3096-81-9 purity| 3096-81-9 application| 3096-81-9 NMR| 3096-81-9 COA| 3096-81-9 structure
A381685 [78338-68-8]
4-(4-Methoxyphenoxy)benzonitrile
Similarity: 1.00
A422255 [188998-47-2]
5-(m-Tolyloxy)isophthalonitrile
Similarity: 0.97
A381685 [78338-68-8]
4-(4-Methoxyphenoxy)benzonitrile
Similarity: 1.00
A422255 [188998-47-2]
5-(m-Tolyloxy)isophthalonitrile
Similarity: 0.97
A381685 [78338-68-8]
4-(4-Methoxyphenoxy)benzonitrile
Similarity: 1.00
A422255 [188998-47-2]
5-(m-Tolyloxy)isophthalonitrile
Similarity: 0.97
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