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CAS No. : | 2920-38-9 | MDL No. : | MFCD00001821 |
Formula : | C13H9N | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | BPMBNLJJRKCCRT-UHFFFAOYSA-N |
M.W : | 179.22 | Pubchem ID : | 18021 |
Synonyms : |
|
Num. heavy atoms : | 14 |
Num. arom. heavy atoms : | 12 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 1.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 56.59 |
TPSA : | 23.79 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | Yes |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -5.08 cm/s |
Log Po/w (iLOGP) : | 2.22 |
Log Po/w (XLOGP3) : | 3.26 |
Log Po/w (WLOGP) : | 3.23 |
Log Po/w (MLOGP) : | 3.0 |
Log Po/w (SILICOS-IT) : | 3.54 |
Consensus Log Po/w : | 3.05 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 2.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.57 |
Solubility : | 0.0479 mg/ml ; 0.000267 mol/l |
Class : | Soluble |
Log S (Ali) : | -3.43 |
Solubility : | 0.066 mg/ml ; 0.000368 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -5.0 |
Solubility : | 0.0018 mg/ml ; 0.00001 mol/l |
Class : | Moderately soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.81 |
Signal Word: | Danger | Class: | 6.1 |
Precautionary Statements: | P261-P302+P352 | UN#: | 3439 |
Hazard Statements: | H302+H312-H331 | Packing Group: | Ⅲ |
GHS Pictogram: |
* 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 |
---|---|---|
83% | With sodium hydride; zinc(II) chloride In tetrahydrofuran; mineral oil at 40℃; for 3h; Inert atmosphere; Sealed tube; | Reduction of Nitriles 1 and 3 to Aldehydes 2 and 4; General Procedure General procedure: To a mixture of NaH (60% dispersion in mineral oil; 60.0 mg, 1.50 mmol) and ZnCl2 (102 mg, 0.750 mmol) in a 25-mL sealed tube was added a solution of nitrile 1 or 3 (0.500 mmol) in THF (2.5 mL). The mixture was sealed and stirred at 40 °C. The reaction was quenchedby following one of the two protocols. Workup protocol 1: Upon full consumption of the nitrile (TLC or GC monitoring), silica gel (2.0 g) was added to the mixture and it was diluted with hexane (10 mL) at 0 °C. The resulting mixture was stirred for 1 h at 24 °C. The mixture was then filtered through layers of cottonand sand and washed with EtOAc. The volatile materials were removedin vacuo from the resulting filtrate. The crude residue was purified by flash column chromatography to give the corresponding aldehyde 2 or 4. Workup protocol 2: Upon full consumption of amide (TLC or GC monitoring), the reaction was quenched with pH 10 ammonium buffer at 0°C and the organic materials were extracted with CH2Cl2 (3 × 20 mL). The combined organic extracts were dried (MgSO4). The volatile materials were removed in vacuo and the resulting crude residue was purified by flash column chromatography to give the corresponding aldehyde 2 or 4. |
With hydrogenchloride; diethyl ether; tin(ll) chloride Erwaermen des Reaktionsprodukts mit H2O; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 5% 2: 94% | With diisobutylaluminum chloride In tetrahydrofuran at 50℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With trifluorormethanesulfonic acid; O-benzenesulfonyl-acetohydroxamic acid ethyl ester In dichloromethane at 23℃; for 24h; Inert atmosphere; | |
99% | With ammonium sulfate; sodium carbonate; sulfur In dimethyl sulfoxide at 120℃; for 10h; Sealed tube; | 17 Example 17 Combine 4-phenylbenzaldehyde (91.0mg, 0.5mmol), ammonium sulfate (66.1mg, 0.5mmol), sodium carbonate (53.0mg, 0.5mmol),Sulfur powder (32.0 mg, 1 mmol) and 0.5 ml of solvent DMSO were put into the reaction tube, and the reaction tube was sealed.The reaction tube was placed in a 120 °C oil bath reaction pot with magnetic stirring for 10 hours. After cooling to room temperature. Then it was extracted with ethyl acetate and the organic phases were combined. The organic phase was washed with saturated brine, and after liquid separation, the organic phase was dried with anhydrous sodium sulfate,After filtering and concentrating the filtrate under reduced pressure, the pure product was separated by thin layer chromatography using ethyl acetate: petroleum ether=1:200 (volume ratio) as the developing solvent. Yellow solid, yield 99% |
99% | With oxygen; ammonium carbonate In dimethyl sulfoxide at 120℃; for 8h; Sealed tube; Green chemistry; | 2.3. Activity test General procedure: The typical experimental procedure for the ammoxidation of aldehydeswith ammonium carbonate was as follows: powdered catalyst (10mg), aldehydes (0.2 mmol), ammonium salt (0.4 mmol), and 2 mL solventwere added into a glass tube (10 mL) under an O2 atmosphere. Themixture in this sealed glass tube was reacted at a suitable temperaturefor determined reaction times. Then, the reaction mixture in the sealedtube was centrifuged to obtain the liquid phase, which was analyzed onan Agilent 7890B gas chromatograph (GC) that was equipped with aflame ionization detector and an HP-5 capillary column (30 m, 0.32 mminner diameter, and 0.25 μm film), and using methylbenzene as an internalstandard. The temperature program of the column oven was asfollows: from an initial temperature of 50 C, the oven was heated to180 C at a rate of 15 Cmin 1 and subsequently heated to 280 C at arate of 20 Cmin 1. The conversion and product selectivity werecalculated as follows. The pure product was isolated by silica-gel column chromatographyusing petroleum ether and ethyl acetate as eluents. The obtained purecompounds were characterized by proton nuclear magnetic resonance(1H NMR) spectroscopy on a BURCKER AVANCE II 500 M spectrometerat 20 C using CDCl3 as the solvent. |
98% | With trifluorormethanesulfonic acid; trimethylsilylazide In acetonitrile at 25℃; for 0.00277778h; Flow reactor; | General procedure: General procedure for synthesis of nitriles from aldehydes incontinuous ow is as follows. Take benzaldehyde as an example,benzaldehyde (0.6 mmol) and TfOH (0.9 mmol) were dissolved in3 mL MeCN and pumped into inlet A. TMSN 3 (0.6 mmol) wasdissolved in 3 mL MeCN and pumped into inlet B (ow rate A:B = 54 m L/min:65 m L/min for 5 s residence time). The whole systemwas maintained at 25C. The ow system was equilibrated (about5 min), then the product stream was quenched and collected in aglass vessel with saturated aqueous NaClO in it. The ow systemwas stopped after the inlet A reduced 0.5 mL. The crude mixturewas dissolved in ethyl acetate and washed with saline solution. Thecombined organic layers were dried over magnesium sulfate,ltered, and concentrated under reduced pressure. The resultingcrude product was puried by ash chromatography on silica gelwith hexane and EtOAc as eluent to afford the product |
95% | With ammonia; oxygen In tert-Amyl alcohol at 40℃; for 24h; Green chemistry; | |
92% | With ammonium hydroxide; 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione In acetonitrile at 20℃; for 2h; | |
85% | With sodium azide; trifluorormethanesulfonic acid In acetonitrile at 20℃; for 0.0333333h; | |
83% | With trimethylsilylazide; zirconium(IV) chloride In acetonitrile at 20℃; for 0.333333h; | |
83% | With O-(4-(trifluoromethyl)benzoyl)hydroxylamine; trifluoroacetic acid In 1,2-dimethoxyethane at 80℃; for 24h; | |
80% | With oxygen; acetonitrile; copper(l) chloride In N,N-dimethyl acetamide at 130℃; for 24h; Schlenk technique; | |
80% | With trifluorormethanesulfonic acid; trimethylsilylazide In acetonitrile at 20℃; for 0.75h; Sealed tube; Inert atmosphere; | 3.3. General Procedure A for the Synthesis of Aromatic Nitriles General procedure: To a solution of an aromatic aldehyde 1 (0.500 mmol, 1.0 equiv) and TMSN3 (115 mg, 1.00 mmol,2.0 equiv) in a premixed HFIP/ACN mixture (2.0 mL, 1:1) in a nitrogen-flushed two dram vial wasadded triflic acid (TfOH; 17.7 L, 0.200 mmol, 0.40 equiv) (exotherm and brisk effervescence due tonitrogen gas evolution was immediately observed). The vial was capped and the reaction mixture wasallowed to stir at rt for 20-75 min. The reaction mixture was concentrated under nitrogen. The residueobtained was suspended in CH2Cl2/hexanes mixture and loaded on a silica gel in a 5 g samplecartridge. Purification using a normal phase silica flash column on a CombiFlash purification systemafforded a corresponding aromatic nitrile 2 upon concentration of appropriate fractions. |
80% | With formic acid; iron(III) trifluoromethanesulfonate; nitromethane; trifluoromethylsulfonic anhydride; triethylamine In acetic acid at 60℃; for 12h; | |
75% | With oxygen; copper(ll) bromide; potassium hexacyanoferrate(III) In N,N-dimethyl-formamide at 150℃; for 12h; Sealed tube; | |
73% | With iron(III) trifluoromethanesulfonate; nitromethane; trifluoromethylsulfonic anhydride; acetic acid; triethylamine In formic acid at 30 - 120℃; | 28 Example 28 p-phenylbenzonitrile Take a reaction tube, add 500-600mg (1.2mmol) of nitromethane, 0.5mL of acetic acid,Trifluoromethanesulfonic anhydride 150-200mg (0.6mmol),30-60 mg (0.75 mmol) of formic acid, stirred at 80-120°C for 4 hours. Then add 50-70 mg (0.3 mmol) of p-phenylbenzaldehyde, 10-20 mg (0.03 mmol) of Fe(OTf)3, and 50-70 mg (0.6 mmol) of triethylamine, and stir for 1-72 hours at 30-70°C. After the reaction, 10 mL of sodium hydroxide solution was added to quench the reaction, extracted with ethyl acetate 3 times, the organic phase was washed with 5 mL of brine, and the organic phases were combined and separated by column chromatography to obtain 42.9 mg of p-phenylbenzonitrile, with a yield of 73%. . |
With pyridine; hydroxylamine hydrochloride; acetic anhydride 1) r.t., 30 min, 2) pyridine, reflux, 1 h; Yield given. Multistep reaction; | ||
With hydroxylamine hydrochloride; acetic anhydride In pyridine | ||
Multi-step reaction with 2 steps 1: sodium tetrahydroborate 2: copper(II) perchlorate hexahydrate; trimethylsilylazide; 2,3-dicyano-5,6-dichloro-p-benzoquinone / 1,2-dichloro-ethane / 2 h / 60 °C | ||
Multi-step reaction with 2 steps 1: hydroxylamine hydrochloride / ethanol; water / 5 h / Reflux 2: N,N-dimethyl-formamide; carbon tetrabromide / acetonitrile / 12 h / Inert atmosphere; Irradiation; Sealed tube | ||
Multi-step reaction with 2 steps 1: hydroxylamine hydrochloride; sodium carbonate / dimethyl sulfoxide / 20 °C 2: sodium carbonate; fluorosulfonyl fluoride / dimethyl sulfoxide / 12 h / 20 °C | ||
Multi-step reaction with 2 steps 1: hydroxylamine hydrochloride; potassium carbonate / 20 °C 2: potassium carbonate; fluorosulfonyl fluoride / 12 h / 20 °C | ||
Multi-step reaction with 2 steps 1.1: sodium acetate / methanol; water / 20 °C 2.1: bis[2-(diphenylphosphino)phenyl] ether; bis(1,5-cyclooctadiene)nickel (0) / 1,4-dioxane / 17 h / 80 °C 2.2: 1 h / 20 °C | ||
Multi-step reaction with 2 steps 1: hydroxylamine / acetonitrile / 2 h / Reflux 2: triethylamine; fluorosulfonyl fluoride / acetonitrile / 0.5 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
21% | Method A 4-Trifluoromethanesulfonylbenzonitrile 21 (126 mg, 0.500 mmol), phenylboronic acid 22 (106.8 mg, 0.6 mmol), (dppf)Ni[P(OPh)3]2 (30.6 mg, 0.0250 mmol), DPPF (13.9 mg, 0.0250 mmol), and potassium phosphate (424 mg, 2.00 mmol) were dissolved in 1,4-dioxane (3 mL) and stirred in a sealed vessel at 100 C under nitrogen for 16 h. The reaction was cooled to RT and water was added (3 mL). The aqueous layer was extracted with dichloromethane (35 mL) and the combined organic layers were washed with water (25 mL) and dried with MgSO4. After filtration, the solvent was removed unde rreduced pressure to give a yellow-brown oil, which was subjected to column chromatography (hexanes/EtOAc 100 : 0 - 97 : 3) to afford a yellow solid, which was then stirred with H2O2 (3mL of a 30% w/w aqueous solution) for 30 min. The mixture was extracted with ethyl acetate (23 mL), dried over MgSO4, and filtered through a plug of silica to afford 4-phenyl benzonitrile 23 as a white solid (18.4 mg, 21 %). The spectral data were in accordance with those reported in the literature.[66] δH (CDCl3, 500 MHz) 7.68 (2H, d, J 8.5, Ar-H), 7.72 (2H, d, J 8.0, Ar-H), 7.59 (2H, d, J 7.5, Ar-H), 7.48 (2H, dd, J 7.5,7, Ar-H), 7.42 (1H, d, J 7.5,7, Ar-H). δC (CDCl3, 125 MHz): 145.7, 139.2, 132.6, 128.7, 127.8, 127.3, 119.0, 110.9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With hydrogenchloride; O,S-diethyl-dithiophosphoric acid In ethyl acetate Ambient temperature; | |
70% | With 2,3,4,5,7,8,9,10-octahydropyrimido[1,2-a]azepin-1-ium acetate; sodiumsulfide nonahydrate In neat (no solvent) at 20℃; for 2h; Green chemistry; | |
70% | With sodiumsulfide nonahydrate In N,N-dimethyl-formamide at 130℃; for 4h; | The general procedure of preparing all thioamides General procedure: Benzonitrile 1a (1 mmol), Na2S*9H2O (1.2 mmol) and DMF (1 mL) were added into a 10 mL bottle. The reactor was placed in a heating magnetic stirrer at 130 °C. After 2.5 h, by adding about 3 mL H2O after the reaction to disperse the solid product, the reaction mixture was extracted with EtOAc (3 x 3 mL), and the mixture was purified by column chromatography. |
69% | With hydrogen sulfide; triethylamine In pyridine for 192h; Ambient temperature; | |
11.2 g (87%) | In hydrochloric acid dioxane | 45.A A. A. Biphenyl-4-carbothioic acid amide According to a modification of Taylor, et al., J. Am. Chem. Soc. 82:2656-2657 (1960), a mixture of commercially available 4-cyanobiphenyl (10.7 g, 60 mmol) and thoiacetamide (9.0 g, 119 mmol) in 4N HCl dioxane (30 mL) was heated to a gently reflux. After 3 h, the reaction was cooled and poured into saturated NaHCO3 (400 mL). After setting for a few hours, the mixture was heated and filtered hot. The brown solid which was not water soluble was collected and dried to give 11.2 g (87%) crude product. The product was used without further purification. 1H NMR (DMSO-d6) δ7.35-8.07 (m, 9H), 9.63 (br s, 2H); MS (m/e) 214 (M+H). |
With diammonium sulfide; ammonia In ethanol at 20℃; for 16h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With tripotassium phosphate tribasic; 3-(2,6-diisopropylphenyl)-1-(2-diphenylphosphanylbenzyl)-3H-imidazol-1-ium chloride In 1,4-dioxane at 80℃; for 6h; | |
100% | With potassium carbonate In N,N-dimethyl-formamide at 110℃; for 1h; | |
100% | With [(5-tBuC6H3-2-OH)CH2(μ-NC4H8N)CH2(5-tBuC6H3-2-OH)]; palladium diacetate; potassium carbonate In methanol at 20℃; Aerobic conditions; |
100% | With C24H26N4O2Pd2*2ClO4(1-); anhydrous sodium carbonate In 1-methyl-pyrrolidin-2-one; lithium hydroxide monohydrate at 100℃; for 2h; Sealed tube; Air; | |
100% | With potassium carbonate; palladium(0) In 1,4-dioxane; lithium hydroxide monohydrate at 60℃; for 0.5h; | |
100% | With tri-tert-butyl phosphine; palladium diacetate; potassium hydroxide In tetrahydrofuran; lithium hydroxide monohydrate at 24℃; for 0.0833333h; Flow reactor; | |
100% | With potassium carbonate In methanol at 60℃; for 0.5h; | |
100% | With potassium carbonate In lithium hydroxide monohydrate at 70℃; for 0.5h; | |
100% | With potassium carbonate In 1,4-dioxane; lithium hydroxide monohydrate at 60℃; for 0.5h; | General procedure for the Suzuki-Miyaura coupling reaction General procedure: A 10 mL round-bottom flask was charged with 4-bromoacetophenone (1j, 1 mmol, 1 eq.), phenylboronic acid (2a, 1.5 mmol, 1.5 eq.), K2CO3 (414 mg, 3 mmol, 3 eq.), H2O (2 mL), and Pd catalyst (0.01 mmol). The flask was stirred at 60°C in air. The reaction was monitored by thin layer chromatography (TLC). After the reaction was complete, the reaction mixture was cooled to room temperature and then simply filtered to recover the catalyst. It was then washed with 10 mL of H2O and ethyl acetate (EtOAc). The organic phase was separated from the aqueous phase, which was extracted three times with 30 mL EtOAc. The organic phases were collected together, dried over MgSO4, and filtered. The solvent was then evaporated under reduced pressure. The pure product was obtained via silica gel column chromatography with an eluent of EtOAc and hexane. The resulting product was analyzed by 1H NMR spectroscopy |
100% | With (1-tert-butyl-4-{2-[(N,N-dimethylamino)methyl]phenyl}-3-phenyl-1H-1,2,4-triazol-4-ium-5-ide)palladium(II) dichloride; potassium carbonate In ethanol at 25℃; for 1h; Inert atmosphere; Schlenk technique; Sealed tube; | |
100% | With potassium carbonate In lithium hydroxide monohydrate; isopropanol at 100℃; for 6h; Inert atmosphere; | 3.3. The Pd(at)NPad2-1.0 catalyzed Suzuki-Miyaura coupling of aryl bromides with phenylboronic acid General procedure: In a typical reaction, an aryl bromide (25.0 mmol), phenylboronic acid (37.5 mmol), Pd(at)NPad2-1.0 catalyst (1.35 mg, 4.0 ppm Pd), K2CO3 (6.9105 g, 50.0 mmol) and 20.0 mL of i-PrOH-water (1:1) were added into a 50 mL pressure tube under Ar. The reaction was performed at 100 °C for 6 h in an oil bath. After the reaction mixture cooled to room temperature, the organic layer was extracted with ethyl acetate (4 × 10.0 mL). The product was isolated by column with silica gel (hexane/ethyl acetate) and analyzed by 1H NMR. |
100% | With potassium carbonate In lithium hydroxide monohydrate; isopropanol at 100℃; for 6h; Inert atmosphere; | 2.4. Typical procedure for Suzuki-Miyaura coupling of arylbromides with phenylboronic acids with Pd(at)PAN-Ad-0.5 General procedure: Aryl bromide (1.0 mmol), phenylboronic acid (1.5 mmol),PdPAN-Ad-0.5 catalyst (13.7 mg, 0.075 mol% Pd), K2CO3(280.5 mg, 2.0 mmol) and i-PrOH/water (2.0 mL, 1:1 volumeratio) were added to a 20-mL pressure tube under argon. Thetube was put into an oil bath at 100 °C and stirred for 6 h. Afterthe reaction mixture was cooled to room temperature, the organiclayer was extracted with ethyl acetate. The crude productwas purified by column chromatography on silica gel. |
100% | With C38H53Cl2N2O2PPd*CH2Cl2; tetrabutylammonium bromide; potassium hydroxide In lithium hydroxide monohydrate at 80℃; for 2h; Schlenk technique; | 2.2. Suzuki-Miyaura cross-coupling reactions General procedure: For a typical reaction, a Schlenk tube was charged with aryl halide (0.5 mmol), phenylboronic acid (0.6 mmol), KOH (2 equiv),Pd catalyst precursor (2.0 mol %), TBAB (1 g), and H2O (5 mL). There action mixture was stirred at 80°C for 2-12 h. After cooling to room temperature, the reaction mixture was extracted with diethyl ether (3 10 mL). The organic solvent was evaporated to dryness under vacuum to give the crude product, which was either analyzed by GC using benzophenone as internal standard or purified by column chromatography. |
100% | With potassium carbonate In 1,4-dioxane; lithium hydroxide monohydrate at 80℃; for 0.5h; Green chemistry; | 4.5.1. General procedure for the Suzuki-Miyaura coupling reaction General procedure: In a typical Suzuki-Miyaura coupling reaction experiment, a 20 mL vial jacket was charged with bromobenzene (1 mmol,0.157 g), phenylboronic acid (1.5 mmol, 0.183 g) and K2CO3(3 mmol, 0.415 g) in 6 mL H2O. After the addition of APPd(0)Sicatalyst (1 mol%, 0.019 g), the reaction mixture was stirred at 80 °C for 4 h. The reaction was monitored by thin layer chromatography(TLC). After completion, the reaction mixture was cooled and 6 mLof ethyl acetate was added, followed by filtration, and washing with10 mL of ethyl acetate and H2O. The ethyl acetate layer was collected and dried with anhydrous magnesium sulfate and dried over in vacuo. The product was purified by silica-gel column chromatographyand analyzed by 1H NMR spectroscopy. |
100% | With tripotassium phosphate tribasic; (dppf)Ni<SUP>(II)</SUP>(o-tolyl)Cl In 1,4-dioxane at 80℃; for 4h; Sealed tube; | |
100% | With potassium carbonate In lithium hydroxide monohydrate; isopropanol at 20℃; for 0.0166667h; Green chemistry; | 2.2 Suzuki-Miyaura Cross-Coupling Reaction General procedure: Aryl halide (0.5mmol), aryl boronic acid (0.6mmol), potassiumcarbonate (1mmol), and 1mg of Fe3O4SB15NHCPd catalyst (contains 3,1 × 10-6 mol% Pd) wereplaced in the reaction tube under air, and 3ml of 2-propanol/water mixture (1:2, v:v) was added and stirred at room temperature.Fe3O4SBA-15NHCPd was separated fromthe reaction mixture by an external magnet after the reaction.Then, 3ml of water and 3ml of DCM were added to thereaction mixture, and the organic phase was separated byextraction and dried over MgSO4.All volatiles evaporatedto obtain the corresponding crude product. |
99% | With Cs2CO3 In toluene at 80℃; | |
99% | With tripotassium phosphate tribasic In ethanol; lithium hydroxide monohydrate at 50℃; for 1h; | |
99% | With tripotassium phosphate tribasic In toluene at 110℃; for 2h; | |
99.8% | With potassium carbonate In toluene at 100℃; for 12h; | |
99% | With potassium carbonate In N,N-dimethyl acetamide at 100℃; for 4h; | |
99% | With 3-(di-tert-butylphosphino)propane-1-sulfonic acid; palladium diacetate; anhydrous sodium carbonate In lithium hydroxide monohydrate; acetonitrile at 23℃; Inert atmosphere; | |
99% | With potassium phosphate tribasic trihydrate In ethanol; lithium hydroxide monohydrate at 50℃; for 7h; | |
99% | With tripotassium phosphate tribasic; (NC5H3(N2C7H4(CH2)3CH3)2)NiBr(1+)*Br(1-)=Ni(NC5H3(N2C7H4(CH2)3CH3)2)Br2; triphenylphosphine In 1,4-dioxane at 100℃; for 24h; | |
99% | With potassium carbonate; palladium (II) chloride In ethanol; lithium hydroxide monohydrate at 20℃; for 0.133333h; | |
99% | With Br(1-)*C28H29BrN5O2Pd(1+); potassium carbonate In lithium hydroxide monohydrate at 100℃; for 3h; | |
99% | With potassium carbonate; palladium (II) chloride In lithium hydroxide monohydrate; N,N-dimethyl-formamide at 20℃; for 0.05h; | |
99% | With C15H23Cl2N4Pd(1+)*Cl(1-); potassium carbonate In lithium hydroxide monohydrate at 120℃; for 1h; | |
99% | With potassium carbonate; palladium (II) chloride In ethanol; lithium hydroxide monohydrate at 20℃; for 0.05h; | General procedure for the Suzuki reaction of aryl bromides with arylboronic acids General procedure: A mixture of aryl bromide (0.5 mmol), arylboronic acid (0.75 mmol), PdCl2 (0.0025 mmol, 0.44 mg), K2CO3 (1 mmol) was stirred in distilled water (2 mL) and ethonal (2 mL) at room temperature in air for the indicated time. After the completion of the reaction, the mixture was quenched by brine (15 mL), extracted with diethyl ether (4×10 mL), dried by anhydrous MgSO4, concentrated under vacuum and the product was afforded by column chromatography on silica gel (200-300 mesh) eluted with petroleum ether and ethyl acetate. |
99% | With potassium phosphate heptahydrate; palladium diacetate In toluene at 75℃; for 0.116667h; | |
99% | With tripotassium phosphate tribasic In methanol at 60℃; for 1.5h; | |
99% | With potassium phosphate tribasic trihydrate In ethanol; lithium hydroxide monohydrate at 60℃; for 0.0833333h; | |
99% | With tripotassium phosphate tribasic; N1,N1,N2,N2-tetrakis[(diphenylphosphino)methyl]ethane-1,2-diamine; palladium (II) chloride In 1,4-dioxane; N,N-dimethyl-formamide at 90℃; for 2h; Inert atmosphere; | |
99% | With C24H30N4O7; potassium carbonate; palladium (II) chloride In lithium hydroxide monohydrate at 20℃; for 1.5h; | |
99% | With 5%-palladium/activated carbon; potassium carbonate In ethanol; lithium hydroxide monohydrate at 20℃; for 0.416667h; | |
99% | With palladium diacetate; anhydrous sodium carbonate In lithium hydroxide monohydrate; N,N-dimethyl-formamide at 35℃; for 0.5h; | General procedure for the Suzuki reaction of aryl halide witharylboronic acids General procedure: A mixture of aryl halide (1 mmol), arylboronic acid (1.5 mmol), Pd(OAc)2 (for aryl bromide 1 mol%, for aryl chloride 2 mol%), and Na2CO3 (2 mmol) was stirred in the mixture of H2O/DMF (3.5: 3 mL) at suitable temperature for indicated time in air. The reaction mixture was cooled to room temperature, and extracted by Et2O (10 mL) for three times. And then the organic phase was combined and evaporated under reduced pressure. The residue was purified on a silica gel (300-400 mesh) column to afford the desired product. |
99% | With potassium carbonate In ethanol; lithium hydroxide monohydrate at 50℃; for 4h; | |
99% | With sodium methoxide In 1,4-dioxane at 100℃; for 25h; Schlenk technique; | |
99% | With potassium carbonate In lithium hydroxide monohydrate at 60℃; for 3h; | |
99% | With potassium carbonate In lithium hydroxide monohydrate; N,N-dimethyl-formamide at 50℃; for 0.5h; | |
99% | With tripotassium phosphate monohydrate; 4,4'-di-tBu-2,2'-dipyridylpalladium(II) dichloride In methanol; lithium hydroxide monohydrate at 80℃; for 2h; | |
99% | With potassium carbonate In lithium hydroxide monohydrate at 20℃; for 1h; | |
99% | With Cs2CO3 In lithium hydroxide monohydrate; N,N-dimethyl-formamide at 80℃; for 2h; | Suzuki-Miyaura Reaction; General Procedure: General procedure: Arylhalide 19 or 22 (1.0 mmol), phenylboronic acid (20; 1.2mmol, 0.146 g), 18 (0.015 mmol, 0.002 g), Cs2CO3 (1.5mmol, 0.489 g), DMF (2.5 mL), and H2O (2.5 mL) wereplaced in a 25 mL round-bottomed flask equipped with amagnetic stirrer. The flask was immersed in an oil bathregulated at 80 or 100 °C for the reaction time indicated inTable 1 or Table 2. After the reaction mixture was cooled tor.t., Et2O (8 mL) and H2O (8 mL) were added to the flask.The resulting mixture was vigorously stirred for 5 min, andthen filtered. The solid 18 collected on the filter was washedwith H2O (10 mL) and Et2O (10 mL) and then dried. Thefiltrate was transferred to a separation funnel and the organicphase was separated and washed with H2O (5 × 25 mL) andbrine (10 mL), and then dried over MgSO4. The solvent wasremoved under reduced pressure and the resulting residuewas analyzed by 1H and 13C NMR spectroscopy. When arylchlorides were used as substrates, the crude products werepurified by silica gel column chromatography. |
99% | With Pd(4,4'-bis(diphenylphosphino)-2,2',6,6'-tetra-methoxy-3,3'-bipyridine)Cl<SUB>2</SUB>; potassium hydroxide In ethanol; dichloromethane at 25℃; for 12h; | |
99% | With potassium carbonate In lithium hydroxide monohydrate; N,N-dimethyl-formamide at 80℃; for 2h; | 2.5. General procedure for the Suzuki reaction of aryl halides witharylboronic acids General procedure: The aryl halide (0.5 mmol), arylboronic acid (0.75 mmol), Cell-NHC-Pd (0.75 mol%), K2CO3(1 mmol) and DMF:H2O (1:1) (2.5 mL)were successively added into a 25 mL round bottom flask. The mixture was stirred vigorously at 80 °C for the varying specific length of time based on each different substrate. After reaction completion, the solid catalyst was filtered off. The filtrate was extracted with ethyl acetate (3 × 5 mL), washed with water and brine three times, and then dried over anhydrous MgSO4. The MgSO4 was then filtered off. After removal of the solvent, the crude product was purified by preparative TLC (eluent: petroleum ether/ethyl acetate, 20/1) to give the desired product and calculate the yield. |
99% | With C31H26N4PPdS(1+)*Cl(1-); anhydrous sodium carbonate In ethanol at 75℃; for 16h; | 2.5.1. General procedure for the Suzuki coupling reactions General procedure: In a typical run, an oven-dried 10 mL round bottom flask wascharged with a known mole percent of catalyst, Na2CO3(1.7 mmol), phenylboronic acid (1.2 mmol) and aryl halide(1 mmol) with the appropriate solvents (4 mL). The flask wasplaced in a preheated oil bath at required temp. After the specifiedtime the flask was removed from the oil bath and water (20 mL)added, followed by extraction with ether (4 10 mL). The combinedorganic layers were washed with water (3 10 mL), driedover anhydrous Na2SO4, and filtered. Solvent was removed under vacuum. The residue was dissolved in hexane and analyzed by GC-MS using Elite-5 columns, which are fused silica capillary columnscoated with 5% diphenyl and 95% dimethyl polysiloxane. |
99.5% | With potassium carbonate In ethanol; lithium hydroxide monohydrate at 80℃; for 1h; | 2.2 Catalysis reaction General procedure: Aryl bromide (0.5mmol, 1 equiv), phenyl boronic acid (0.75mmol, 1.5 equiv), K2CO3 (1.5mmol, 3 equiv) and Pd/DBU-CCG catalyst (0.5mol%) were dissolved in a mixture of 8mL of H2O: EtOH (1:1 in volume) in a 20mL glass reactor, which was sealed with a Teflon screw cap and stirred at 80°C for the time indicated. The conversion of bromobenzene was analyzed by gas chromatography (GC) with octane as interior label. For 4-bromoanisole or 4-bromobenzonitrile as substrate, upon the completion of the reaction period, the reaction mixture was added to brine (15mL) and extracted with ethyl acetate (3×15mL). The organic solvent was removed under vacuum, and the product was isolated by short-column chromatography using petroleum ether:ethyl acetate as the eluent to calculate the isolated yield. |
99% | With potassium-t-butoxide In ethanol; lithium hydroxide monohydrate at 25℃; for 1h; | |
99% | With potassium carbonate In ethanol; lithium hydroxide monohydrate at 50℃; for 3h; | |
99% | With tripotassium phosphate tribasic In N,N-dimethyl-formamide at 120℃; for 6h; Inert atmosphere; Schlenk technique; Green chemistry; | |
99% | With potassium phosphate tribasic trihydrate In ethanol; lithium hydroxide monohydrate at 80℃; for 0.5h; | 2.3. Catalytic tests General procedure: In a typical Suzuki coupling, 1 mmol halide, 1.2 mmol phenylboronic acid, 1.5 mmol K3PO4·3H2O, 0.01 g catalyst, 3 mL water and 2 mL ethanol were reacted at 80-120 °C with constant stirring. A typical Heck coupling used 1 mmol halide, 1.2 mmol vinylic substrate, 1.5 mmol K3PO4·3H2O, 0.01 g catalyst and 5 mL NMP (1-methy-2-pyrrolidinone) at 130-140 °C. In atypical Sonogashira coupling, 1 mmol halide, 1.2 mmol benzyne,1.5 mmol K3PO4·3H2O, 0.01 g catalyst and 5 mL solvent were used at 120-140 °C. After each reaction, the catalyst was removed by centrifugation and analyzed by gas chromatography (GC-1690, Kexiao Co.) using a flame ionization detectorand a DB-1 capillary column. |
99% | With anhydrous sodium carbonate at 80℃; for 0.666667h; | |
99% | With 4Cl4Pt(2-)*C72H128N16O12S8Si8(8+); potassium carbonate In lithium hydroxide monohydrate at 100℃; for 4h; | |
99% | With C37H28N8O*2Cl(1-)*Pd(2+); potassium carbonate In ethanol at 70℃; for 2h; | 2.3. General procedure for Suzuki-Miyaura reaction General procedure: Arylhalide (5.0 mmol) and phenylboronic acid (5.0 mmol), K2CO3 (5.0 mmol) and X-Pd3L (0.005 mol% Pd loading) were added to a solutionof 12 mL EtOH under ambient atmosphere. The mixture was stirred at 70 °C for 2 h. After cooling, H2O (10 mL) was added into the resultant mixture and the product was extracted by ethyl acetate (3 × 10 mL). The organic phase was combined and dried over Na2SO4. After removal of solvent, the product was dried at 60 °C. In most cases, the products are pure (analyzed by 1H NMR spectroscopy) because it is an equal stoichiometric reaction and the substrates are completely converted into product. If the product is impure, the purification can be performed ona silica gel chromatography (hexane:ether = 60:1 as an eluent). All products were confirmed by 1H and 13C NMR and compared with literatures (see SI). For the recycled experiment, the xerogel catalyst was recovered by centrifugation and washed with EtOH (3 × 4 mL) after reaction, then dried in air. |
99% | With potassium carbonate In ethanol; lithium hydroxide monohydrate at 50℃; for 2.5h; Inert atmosphere; Schlenk technique; | 2.4. General procedure for Suzuki-Miyaura coupling reaction General procedure: A Schlenk tube was charged with a suspension of aryl halide (1.0mmol), arylboronic acid (1.2 mmol), potassium carbonate (276 mg,2.0 mmol) and Pd/HCCP-DABP (20 mg, 0.3 mol%) in EtOH-H2O (3 mL,v:v=1:1), evacuated, and backfilled with nitrogen. The resulting reaction mixture was stirred at 50 °C for 2.5 h. After completion of the reaction,the mixture was cooled and extracted with CH2Cl2. The combined organic phase was dried, evaporated and purified by column chromatographyon silica gel to give the coupling product. The aqueous phasewas filtered and the solid was washed with CH2Cl2 and reused in further reactions as the recovered catalyst. |
99% | With potassium carbonate In ethanol; lithium hydroxide monohydrate at 50℃; for 4h; | The spirofluorene pyridine palladium nanoparticles prepared as described in Example 1 above were used as catalysts for the reaction reaction: 1.0 mmol of 4-bromobenzonitrile,1.2 mmol of phenylboronic acid and3.0 mmol K2CO3,In an air atmosphere in a H2O / EtOH mixed solvent,The mixed solvent consisted of 4 mL of water and 3 mL of ethanol (EtOH) at a reaction temperature of 50 ° C and a reaction time of 4 h. The product was separated by column chromatography in a yield of 99%. |
99% | With bis(acetonitrile)palladium(II) chloride; C95H120N20O10(10+)*10F6P(1-); potassium carbonate In ethanol at 50℃; for 1.5h; | General procedure for the Suzuki coupling reactions General procedure: In a typical run, a mixture of aryl bromide (0.50 mmol),phenylboronic acid (0.55 mmol), K2CO3 (1.5 mmol),0.2 mol% ligand, 1 mol% PdCl2(CH3CN)2 in 1.5 mL of ethanol were stirred at 50 C for 1.5 h under air. Solvent ethanol was removed completely under vacuum degree0.09 MPa at 45 C to give a crude product. The pure product was isolated by column chromatography on silica. |
99.2% | With potassium phosphate heptahydrate; C52H44Cl4N8O12Pd4 In toluene at 60℃; for 2h; | |
99% | With potassium carbonate In lithium hydroxide monohydrate; N,N-dimethyl-formamide at 50℃; for 0.5h; Sealed tube; Microwave irradiation; | 4. General Procedure for the Suzuki Coupling Reaction of Aryl Halides with Phenylboronic Acid General procedure: Aryl halides (1 mmol), phenylboronic acid (1.2 mmol, 1.2 equiv), and K2CO3 (1.5 mmol, 1.5 equiv) were dissolved in water and DMF (2:1, v/v, 3 mL), followed by addition of the three-alkoxy-substituted oxime palladacycle resin (1 mol% Pd: 17.1mg). The mixture was microwave-irradiated under 40W at various temperatures (50~100 °C) for 30 minutes in a sealed vessel (10 mL). After filtration and washing the resins with distilled water (1 mL * 5) and diethyl ether (1 mL * 5), the filtrate was poured into diethyl ether. The organic layer was washed with water and dried over MgSO4, and the solvent was evaporated under reduced pressure. The crude product was identified by gas chromatography/mass spectroscopy (GC-MS). The same procedure was performed for the Suzuki coupling reactions of aryl halides (1 mmol) and potassium phenyltrifluoroborate (1.2 mmol, 1.2 equiv). For the reactions in water, all the procedures were the same but only water (3 mL) was used as a solvent with the phase transfer catalyst, TBAB (1 mmol). |
99% | With [bis(dichloropyridyl )]{(S)-3,3′-((2,2′-dimethoxy-[1,1′-binaphthalene]-3,3′-diyl)bis(methylene))bis(1-(2,6-diisopropylphenyl)-2,3-dihydro-1H-imidazolidene)}dipalladium(II); potassium hydroxide In 1,4-dioxane at 65℃; for 24h; | |
99% | With potassium carbonate In ethanol at 80℃; for 0.666667h; | |
99% | With potassium carbonate In ethanol; lithium hydroxide monohydrate at 100℃; for 15h; Green chemistry; | |
99% | With [PdBr2(1-butyl-3-methylimidazol-2-ylidene)(1-methylimidazole)]; potassium carbonate In lithium hydroxide monohydrate; isopropanol at 80℃; for 1h; Schlenk technique; Inert atmosphere; | 2.4. The Suzuki-Miyaura reaction procedure General procedure: All lab glassware and stirring bars were treated with aqua regiato remove any possible palladium contamination before applyingthem to catalytic reactions.The Suzuki-Miyaura reactions were carried out in a 50mlSchlenk tube equipped with a stirring bar. The solid substrates,phenylboronic acid (1.1 mmol, 0.134 g), K2CO3 (1.0 mmol, 0.138 g)and palladium catalyst (0.005 mmol) were weighed and placed inthe Schlenk tube. Next, solvent (1.5 ml H2O 1.5 iPrOH or3.0 ml H2O) was added. The Schlenk tube was cooled down in theliquid nitrogen, evacuated using a membrane pump and filled withdinitrogen. This procedure was repeated three times. At the end, inthe flow of dinitrogen, 2-bromotoluene (1.0 mmol, 0.17 g, 120 ml) was added. The Schlenk tube was tightly closed with a rubberseptum and the reaction mixture was stirred at 80 °C for 1 h. Afterthat time, water (3 ml) was added to facilitate phase separation,and the organic products were extracted with 21 ml of diethyl ether(3 7 ml, time of extraction 3 5 min). The extract was GC-MSanalyzed with dodecane (0.44 mmol, 100 ml) as the internal standard.All the reactions were carried out at least two times.To obtain time-profile of reaction the reaction mixture wascooled down in liquid nitrogen immediately after appropriate time(2.5 min, 5 min etc.) to stop the reaction. Next, the standardextraction was used to separate reaction products for GC analysis. |
99% | With graphene oxide supported Pd (II)/Fe (III) bimetallic catalytic monolayer catalyst In lithium hydroxide monohydrate at 70℃; for 2h; Alkaline conditions; | |
99% | With potassium carbonate In lithium hydroxide monohydrate; N,N-dimethyl-formamide at 100℃; for 6h; | |
99% | Stage #1: 4-bromobenzenecarbonitrile; phenylboronic acid With potassium carbonate In dimethyl sulfoxide at 70℃; for 0.5h; Stage #2: for 0.5h; | 2.2.5. General procedure of Suzuki reaction of arylhalides with arylboronicacids by PdBPACNC nanocatalysts General procedure: To synthesize biaryl derivatives using Suzuki reaction via C-C arylationreactions, aryl halide (1 mmol), arylboronic acid (1.6 mmol)and K2CO3 (3 mmol) in DMSO (10 mL) were placed into a round bottom flask containing 10 mg of the PdBPACNC as nanocatalyst. Theabove obtained mixture was stirred at 70 °C for a definite time which isrequired for each substrate. After completion of the reaction, the solidcatalyst was filtered and washed 5 times with deionized water andabsolute ether and kept for reusability study of the catalyst under resemblingreaction conditions. The filtrate was extracted with ethylacetate (3×5 mL), washed with deionized water and dried by anhydrousMgSO4. After that, MgSO4 was filtered, the solvent was evaporatedand the resulting product was purified by preparative TLC (eluent:petroleum ether/ethyl acetate, 20/1) (scheme 1). |
99% | With (1-(2,6-diisopropylphenyl)-2,3-dihydro-1H-imidazol-2-yl)(methyl(λ1-oxidaneyl)diphenyl-λ5-phosphaneyl)palladium(II) chloride; Cs2CO3 In methanol; dichloromethane; toluene at 100℃; Glovebox; | |
99% | With palladium diacetate; N,N-diisopropylamine In lithium hydroxide monohydrate at 100℃; for 0.0833333h; Sealed tube; Green chemistry; | |
99% | With C27H23ClNO3PPd; potassium carbonate In ethanol; lithium hydroxide monohydrate at 50℃; for 1h; Schlenk technique; | 3.3. General procedure for Suzuki-Miyaura cross-coupling reactions General procedure: A 10 mL Schlenk tube was charged with complex 3b , ArBr (0.5 mmol), ArB(OH) 2 (0.6 mmol), K 2 CO 3 (138.2 mg, 1.0 mmol), and solvent (3 mL). The mixture was stirred at specified temper- ature under air for a certain time (monitored by TLC). Upon com- pletion of the reaction, the mixture was let to cool down (for the reaction being conducted at room temperature this cooling step was unnecessary) and quenched with saturated brine, and then extracted with ethyl acetate (EtOAc) and dried over Na 2 SO 4 . Af- ter filtration and evaporation of the solvent, the resulting residue was purified by column chromatography on silica gel with EtOAc- petroleum ether as the eluent to give the biaryl products. All the products are known compounds and identified by 1 H NMR spec- troscopy. |
99% | With C30H32N4O12P2Pd; potassium carbonate In ethanol; lithium hydroxide monohydrate at 80℃; for 12h; | 2.2. General procedure for conducting Suzuki-Miyaura coupling reaction General procedure: Aryl halide (0.5 mmol), arylboronic acid (0.75 mmol), K2CO3 (0.75mmol), and the Pd(L8)2 catalyst (0.65 mol%) were added to a 5 ml flaskcontaining a mixture of solvents (H2O:EtOH with 1:1 ratio, 2 mL). Thereaction mixture was stirred at R.T. for aryl iodides and aryl bromidesand 80 C for aryl chloride for 24 h. The progress of the coupling reactionwas monitored by GC. Then, the crude product was extractedusing ethyl acetate (3 × 5 mL). The products were purified using columnand plate chromatography on silica gel. |
99% | Stage #1: 4-bromobenzenecarbonitrile; phenylboronic acid With sodium methoxide In ethanol Inert atmosphere; Stage #2: In ethanol at 60℃; for 1h; Inert atmosphere; | 4.5.1. Catalytic studies for Suzuki-Miyaura reactions General procedure: In glass tubes of a Radleys Carousel 12 Plus StationTM fitted witha water-cooled aluminum reflux head and septa, 16 mL of an absoluteEtOH solution containing p-halogenoacetophenone (0.05 M,1 eq), phenylboronic acid (0.06 M, 1.2 eq) and MeONa (0.075 M,1.5 eq) were added. The reaction mixtures were stirred and heatedat 25 C or 60 C under nitrogen atmosphere for 30 min. Then, thepalladium catalyst (8 10-4 mmol Pd, 5 10-5 M, 0.001 eq) wasadded. The mixture was vigorously stirred and kept at 60 C for1 h under nitrogen. Then, an aliquot (ca. 0.5 mL) of the reactioncrude was taken at different reaction times and quenched in a vial filled with water/ethyl acetate mixture (2:1.5, 3.5 mL) and withnaphthalene (0.09 mmol) as standard |
98% | With anhydrous sodium carbonate In lithium hydroxide monohydrate at 50℃; for 0.3h; | |
98% | With anhydrous sodium carbonate In lithium hydroxide monohydrate; propan-2-one at 35℃; for 0.333333h; | |
98% | With phenyl carbamate; potassium carbonate In ethanol at 20℃; for 2h; | |
98% | With Cs2CO3 In toluene at 80℃; for 16h; | |
98% | With potassium fluoride; (R)-N-(2-methoxybenzylidene)-1-phenylethanamine; palladium diacetate In tetrahydrofuran at 0 - 35℃; for 2.5h; Inert atmosphere; | |
98% | With potassium phosphate tribasic trihydrate; palladium diacetate In lithium hydroxide monohydrate; Aminol at 20℃; for 0.2h; | |
98.3% | With tripotassium phosphate tribasic; palladium diacetate; (E)-2-methoxy-6-(((pyridin-2-ylmethyl)imino)methyl)phenol In toluene at 85℃; for 2h; Inert atmosphere; | |
98.1% | With anhydrous sodium carbonate In lithium hydroxide monohydrate at 100℃; | |
98% | With potassium carbonate In lithium hydroxide monohydrate; N,N-dimethyl-formamide at 80℃; for 5h; | |
98% | With tetrabutylammonium bromide; anhydrous sodium carbonate In lithium hydroxide monohydrate at 100℃; for 2h; | |
98% | With C30H38Cl2N8Pd(2+)*2Cl(1-); tetrabutylammonium bromide; potassium carbonate In lithium hydroxide monohydrate at 60℃; for 12h; | General procedure for Suzuki-Miyaura cross-coupling reaction of arylboronic acid with aryl halide General procedure: Aryl halide (0.5 mmol), arylboronic acid (0.6 mmol), K2CO3 (103 mg, 0.75 mmol), H2O (1.0 mL) and TBAB (1.0 g) was added into a 25 mL schlenk flask. The catalyst (3.8 mg, 1.0 mol%) was added to the mixture, then the reactor was stirred at 60 oC for 12 h. After the reaction was completed, the mixture was extracted with diethyl ether, and the combined organic layer was dried over anhydrous Na2SO4 and was subsequently purified by flash chromatography using silica gel (hexane) yielding the desired products. |
98.2% | With dichloro[9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene]palladium(II); triethylamine In dichloromethane; acetonitrile at 20℃; for 24h; | Catalytic activity of 1a-1d in SuzukieMiyaura cross-coupling reaction Solutions of aryl bromides (2 mmol) in dichloromethane(10 cm3) and aryl boronic acids (2 mmol) in acetonitrile (20 cm3) were mixed together. The base triethylamine (6 mmol) and the respective catalyst (0.004 mmol) in dichloromethane (5 cm3) were then added to the solution and stirred at room temperature. The reactions were monitored by TLC and the products were isolated by silica gel column chromatography using ethyl acetate and hexaneas eluents. The products were characterised by 1H NMR, masss pectrometry and melting point determination followed by their comparison with the standard literature data. In order to study the recycling experiments, the organometallic residues of 1a-1d alongwith the silica gel were collected from the chromatographic column and refluxed in acetonitrile to dissolve the residue to get a solution.The silica gel was separated by filtration and the residue was recovered by removing the solvent in vacuum. The residue wasreused by maintaining the similar experimental conditions as described above. |
98% | With Ph2P(CH2CH2O)22CH3; triethylamine; palladium (II) chloride In lithium hydroxide monohydrate at 100℃; for 0.5h; Inert atmosphere; | |
98% | With N,N,N-tributylbutan-1-aminium fluoride; potassium carbonate In lithium hydroxide monohydrate at 100℃; for 2h; | |
98% | With (BeDABCO)<SUB>2</SUB>Pd<SUB>2</SUB>Cl<SUB>6</SUB>; potassium carbonate In ethanol at 20℃; for 0.2h; | |
98% | With 4-methoxy-6-(((methyl-2-pyridinylmethyl)imino)methyl)phenol; palladium diacetate; potassium hydroxide In ethanol; lithium hydroxide monohydrate for 3h; Reflux; | |
98% | With [Zn4O(2-aminoterephthalate)2.79(2-pyridyl-imine terephthalate-PdCl2)0.21]; potassium carbonate In ethanol; lithium hydroxide monohydrate at 80℃; for 2h; | |
98% | With C34H54N2O2; palladium diacetate; potassium carbonate In lithium hydroxide monohydrate; propan-2-one for 3h; Reflux; Green chemistry; | |
98% | With Pd6(1,3,5-tris(4’-pyridyloxadiazole)-2,4,6-triethylbenzene)8(NO3)12; potassium carbonate In ethanol; lithium hydroxide monohydrate at 60℃; for 1h; Green chemistry; | |
98% | With 5%-palladium/activated carbon; 1,3-bis(2,6-diisopropylphenyl)imidazolidinium chloride; sodium hydroxide; phosphorous acid trimethyl ester In ethanol at 80℃; for 1h; Inert atmosphere; | |
98% | With C28H37Cl2N3Pd; potassium carbonate In methanol; lithium hydroxide monohydrate at 20℃; for 24h; | 4.7. General procedure for the investigation of the effect of catalystloading, base, solvent, time and substrate scopes on Suzuki-Miyaura cross coupling reaction (Tables S1-S5, Tables 4 and 5) General procedure: In the air condition, hexamethylbenzene (0.05 mmol, 0.0081 g,0.1 equiv), aryl halide (0.5 mmol, 1 equiv), aryl boronic acid(0.6 mmol, 1.2 equiv), base (1.1 mmol, 2.2 equiv) and solvent wassubsequently added into a 10 mL vial equipped with a magneticstir bar. The 5 mM Pd catalyst solution in MeOH was added asindicated in the table. The reaction vial was capped and vigorouslystirred at room temperature for desired time as indicated. Thereaction mixture was extracted with CH2Cl2 (3 10 mL), washedwith water (2 10 mL), brine (1 10 mL) and dried over Na2SO4.The combined organic phase was then concentrated to afford thecrude coupling product. The reaction was monitored by GC-FIDbased on integration relative to hexamethylbenzene as an internalstandard. The crude product was finally isolated by columnchromatography (0e10%: EtOAc/hexane) to afford the desiredproduct. |
98% | With C18H20Cl2N4O4Pd; Cs2CO3 In ethanol at 80℃; for 0.25h; Microwave irradiation; | |
98% | With C23H35N4O4Pd(1+)*Br(1-); potassium carbonate In lithium hydroxide monohydrate at 100℃; for 0.25h; | |
98% | With C34H26Cl2Fe2N2O6Pd2S2(2-)*2Na(1+); sodium hydroxide In lithium hydroxide monohydrate at 60℃; for 4h; | |
98% | With tetrabutylammonium bromide; potassium carbonate In lithium hydroxide monohydrate at 80℃; for 12h; Green chemistry; | |
98% | With potassium carbonate In lithium hydroxide monohydrate; N,N-dimethyl-formamide at 100℃; for 3h; Green chemistry; | |
98% | With C48H67N10(1+)*Cl(1-); potassium carbonate; palladium (II) chloride In lithium hydroxide monohydrate; N,N-dimethyl-formamide at 110℃; for 3h; | |
98% | With palladium diacetate In lithium hydroxide monohydrate at 20℃; for 0.166667h; Green chemistry; | |
98% | With tripotassium phosphate tribasic; N,N,N′,N′-tetra(diphenylphosphinomethyl)pyridine-2,6-diamine; palladium (II) chloride In o-dimethylbenzene at 90℃; for 2h; Inert atmosphere; Schlenk technique; | 2.1. General procedure of Suzuki coupling reactions K3PO4 (212 mg, 1 mmol),aryl halides (0.5mmol) and phenylboronicacid (0.75 mmol) were added successively into a dried Schlenk tubewith a magnetic bar under nitrogen. Then a N,N-dimethylacetamide (DMA 0.05 mL) solution of tetraphosphine TPPDA (0.0005 mmol) andPdCl2 (0.0005 mmol), which was reacted at 100 °C for 1 h prior to use,was added into the mixture. Afterwards, o-xylene (3 ml) was addedwith syringe. After being stirred for the required time in the preset con-ditions, the reaction mixture was cooled to room temperature. The mix-ture solution was extracted with ethyl acetate (3 5 mL). Combinedorganic phase was washed with brine (3 5 mL) and dried over anhy-drous MgSO4. The dried solution was ltered and puried by silica gelchromatography (petroleum ether 60-90 °C) to give a correspondingproduct. Reaction condition: aryl halides 0.5 mmol, phenylboronic acid 0.75 mmol, K3PO4 1.0mmol, o-xylene 3 mL, catalyst PdCl2/TPPDA = 1/1, 90 °C, under nitrogen, GC yields. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With tris-(dibenzylideneacetone)dipalladium(0); Py2NPtBu2; sodium tertiary butoxide In tetrahydrofuran at 60℃; for 24h; | |
100% | With Cs2CO3 In 1,4-dioxane at 80℃; for 0.5h; | |
100% | With C38H53Cl2N2O2PPd*CH2Cl2; tetrabutylammonium bromide; potassium hydroxide In lithium hydroxide monohydrate at 80℃; for 6h; Schlenk technique; | 2.2. Suzuki-Miyaura cross-coupling reactions General procedure: For a typical reaction, a Schlenk tube was charged with aryl halide (0.5 mmol), phenylboronic acid (0.6 mmol), KOH (2 equiv),Pd catalyst precursor (2.0 mol %), TBAB (1 g), and H2O (5 mL). There action mixture was stirred at 80°C for 2-12 h. After cooling to room temperature, the reaction mixture was extracted with diethyl ether (3 10 mL). The organic solvent was evaporated to dryness under vacuum to give the crude product, which was either analyzed by GC using benzophenone as internal standard or purified by column chromatography. |
99% | With potassium carbonate; 2-(di-tert-butyl-phosphino)-1-phenyl-1H-pyrrole In toluene at 60℃; | |
99% | With tripotassium phosphate tribasic; 3-(2,6-diisopropylphenyl)-1-(2-diphenylphosphanylbenzyl)-3H-imidazol-1-ium chloride In 1,4-dioxane at 80℃; for 12h; | |
99% | With tripotassium phosphate tribasic In isopropanol at 80℃; for 4h; | |
99% | With anhydrous sodium carbonate In tetrahydrofuran; lithium hydroxide monohydrate at 23℃; | |
99% | With C12H10N3OPol; tetrabutylammonium bromide; palladium diacetate; potassium carbonate In lithium hydroxide monohydrate at 100℃; for 15h; | |
99% | With P(C6H4)CH(C(CH3)C(Si(CH3)3))2; [Pd(C6H4C5H(CH3)2(Si(CH3)3)2P)2]; potassium carbonate In toluene at 80℃; for 1h; Inert atmosphere; | |
99% | With tripotassium phosphate tribasic; (NC5H3(N2C7H4(CH2)3CH3)2)NiBr(1+)*Br(1-)=Ni(NC5H3(N2C7H4(CH2)3CH3)2)Br2; triphenylphosphine In 1,4-dioxane at 100℃; for 24h; | |
99% | With (η3-2-methylallyl)Pd(N3)(1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene); Cs2CO3 In methanol at 80℃; for 1.5h; Schlenk technique; | |
99% | With potassium carbonate In lithium hydroxide monohydrate; isopropanol at 100℃; for 18h; Inert atmosphere; | 3.2. The Pd(at)NPad2-1.0 catalyzed Suzuki-Miyaura coupling of aryl chlorides with phenyboronic acid General procedure: Typically, an aryl chloride (2.0 mmol), phenylboronic acid (3.0 mmol), Pd(at)NPad2-1.0 catalyst (5.4 mg, 0.02 mol% Pd), K2CO3 (552.8 mg, 4.0 mmol) and 4.0 mL of i-PrOH/water (1:1) were added into a 25 mL pressure tube under Ar. The reaction mixture was stirred at 100 °C for 18 h in an oil bath. After the reaction mixture cooled down to room temperature, the product was isolated by column with silica gel and analyzed by 1H NMR. |
99% | With potassium carbonate In lithium hydroxide monohydrate; isopropanol at 100℃; for 18h; Inert atmosphere; | 2.3. Typical procedure for Suzuki-Miyaura coupling of aryl chlorides with phenylboronic acids using Pd(at)PAN-Ad-0.5 General procedure: Aryl chloride (1.0 mmol), phenylboronic acid (1.5 mmol),PdPAN-Ad-0.5 catalyst (13.7 mg, 0.075 mol% Pd), K2CO3(280.5 mg, 2.0 mmol) and i-PrOH/water (2.0 mL, 1:1 volumeratio) were added to a 20-mL pressure tube under argon. After the tube was heated at 100 °C for 18 h with stirring in an oilbath, the reaction mixture was cooled to room temperature.The crude product was purified by column chromatography onsilica gel and analysed by 1H NMR spectroscopy to confirm the product. |
99% | With tripotassium phosphate monohydrate; C42H37N5NiO4; 1,3-bis(2,4,6-trimethylphenyl)imidazolinium chloride In toluene at 100℃; for 8h; Schlenk technique; Inert atmosphere; | |
98% | With caesium fluoride In 1,4-dioxane at 130℃; for 27h; | |
98% | With potassium fluoride; tetrabutylammonium bromide at 100℃; for 3h; | |
98% | With potassium fluoride; tetrabutylammonium bromide at 100℃; for 3h; | |
98% | With tetrabutylammonium bromide; potassium carbonate In N,N-dimethyl-formamide at 120℃; for 18h; | |
98% | With [PdCl(C3N2(C6H5)(C6H4)(C6H3(C3H7)2)2)]2; Cs2CO3 In 1,4-dioxane at 25℃; for 2h; Inert atmosphere; | |
98% | With C27H30ClN3O4PPdS(1+); potassium carbonate In ethanol at 25℃; for 0.833333h; | General procedure: To a solution of catalyst 1 or 2 (0.2 mol %) in EtOH (3 mL) were added phenylboronic acid (146 mg, 1.2 mmol), aryl halide (1 mmol) and K2CO3 (276 mg, 2.0 mmol) and the mixture was allowed to stir at ambient temperature for minutes as described in Table 1. After completion of the reaction, water (15 mL) was added and the organic materials were extracted with CH2Cl2. The organic layer was washed with water, dried over anhydrous Na2SO4 and filtered. Solvent was removed under vacuum and the residue was purified by flash chromatography using n-hexane-EtOAc to afford pure biaryl compound. |
98% | With palladium diacetate; anhydrous sodium carbonate In lithium hydroxide monohydrate; N,N-dimethyl-formamide at 100℃; for 24h; | General procedure for the Suzuki reaction of aryl halide witharylboronic acids General procedure: A mixture of aryl halide (1 mmol), arylboronic acid (1.5 mmol), Pd(OAc)2 (for aryl bromide 1 mol%, for aryl chloride 2 mol%), and Na2CO3 (2 mmol) was stirred in the mixture of H2O/DMF (3.5: 3 mL) at suitable temperature for indicated time in air. The reaction mixture was cooled to room temperature, and extracted by Et2O (10 mL) for three times. And then the organic phase was combined and evaporated under reduced pressure. The residue was purified on a silica gel (300-400 mesh) column to afford the desired product. |
98% | With tripotassium phosphate tribasic In N,N-dimethyl-formamide at 120℃; for 12h; Inert atmosphere; Schlenk technique; Green chemistry; | |
98% | With potassium carbonate In ethanol; lithium hydroxide monohydrate at 25℃; for 1.5h; Schlenk technique; | |
98% | With tripotassium phosphate tribasic; C46H52Cl3N3O2Pd In tetrahydrofuran; lithium hydroxide monohydrate at 60℃; for 4h; | |
97% | With tripotassium phosphate tribasic; di(1-adamantyl)allylphosphonium bromide In toluene at 100℃; for 20h; | |
97% | Stage #1: phenylboronic acid With tripotassium phosphate tribasic; N,N-diisopropyl 2-dicyclohexylphosphino-4-(3'-nitrophenyl)benzamide; palladium diacetate In tetrahydrofuran at 23℃; for 0.0166667h; Inert atmosphere; Stage #2: 4-chlorobenzonitrile In tetrahydrofuran; lithium hydroxide monohydrate at 23℃; for 36h; Inert atmosphere; | |
97% | With 5%-palladium/activated carbon; 1,3-bis(2,6-diisopropylphenyl)imidazolidinium chloride; sodium hydroxide; phosphorous acid trimethyl ester In ethanol at 80℃; for 3h; Inert atmosphere; | |
97% | With tripotassium phosphate tribasic; trans-chloro-(1-naphthyl)bis[tris-(4-methoxyphenyl)phosphane]-nickel(II) In 1,4-dioxane; lithium hydroxide monohydrate at 100℃; for 1h; Inert atmosphere; | General procedure for NiCl(MOTPP)2(1-naphthyl) catalyzed cross-coupling reaction General procedure: An oven-dried reaction tube was charged with Ni(MOTPP)2(1-naphthyl)Cl (2mol%, relative to aryl chloride), K3PO4 (3 equiv., relative to aryl chloride), and phenylboronic acid (1.5 equiv., relative to aryl chloride). Solid aryl chlorides (0.5mmol) were also added at this time. The tube was evacuated and purged with nitrogen for three times. 1,4-dioxane (2mL) and degassed water (0.2mL) were added via syringe. Liquid aryl chlorides were also added via syringe with the solvents. The mixture was stirred at 100°C for 1h under a nitrogen atmosphere, and then cooled to room temperature. The reaction mixture was extracted with ethyl acetate, and the organic layers were dried over anhydrous Na2SO4. The organic phase was evaporated under reduced pressure, and the residue was purified by column chromatography on silica gel with hexane/ethylacetate as the eluent to afford the desired product. The products were identified by gas chromatography and NMR spectra. |
97% | With anhydrous sodium carbonate In lithium hydroxide monohydrate at 25℃; for 1.5h; | |
97% | With tripotassium phosphate tribasic; C50H63Cl2N3Pd In ethanol at 80℃; for 4h; | |
97% | With tripotassium phosphate tribasic; tetrabutylammonium bromide In lithium hydroxide monohydrate at 95℃; for 20h; | |
96% | With glucosamine-based dicyclohexylarylphosphine; anhydrous sodium carbonate In ethanol; lithium hydroxide monohydrate; toluene at 80℃; | |
96% | With Cs2CO3 In toluene at 80℃; for 12h; | |
96% | With Cs2CO3 In 1,4-dioxane for 1h; Heating; | |
96% | With tripotassium phosphate tribasic In 1,4-dioxane for 12h; Heating; | |
96% | With 2-chloro-1,3-bis(2,6-diisopropylphenyl)-1,3,2-diazaphospholidine; tris-(dibenzylideneacetone)dipalladium(0); caesium fluoride In 1,4-dioxane at 80℃; for 21h; Inert atmosphere; | |
96% | With potassium phosphate tribasic trihydrate; C21H26ClN2OPd In Aminol at 130℃; for 12h; | |
96% | With bis(acetonitrile)palladium(II) chloride; C32H25NP2; sodium hydroxide In N,N-dimethyl-formamide at 125℃; for 3.5h; Inert atmosphere; | |
96% | With tetrabutylammonium bromide; anhydrous sodium carbonate In lithium hydroxide monohydrate at 120℃; for 10h; | |
96% | With N,N,N-tributylbutan-1-aminium fluoride; potassium carbonate In lithium hydroxide monohydrate at 100℃; for 22h; | |
96% | With tripotassium phosphate tribasic; rac-2,8-bis(dicyclohexylphosphanyl)-4,10-dimethyl-6,12-dihydro-5,11-methanodibenzo[b,f][1,5]diazocine (2c); palladium diacetate In toluene at 90℃; for 1.5h; Schlenk technique; Inert atmosphere; | |
96% | With [(N,N′-bis-(2,6-di(isopropyl)phenyl)imidazol-2-ylidene)PdCl2(indazole)]; sodium hydroxide In ethanol at 20℃; for 4h; Sealed tube; | |
96% | With potassium carbonate at 60℃; for 2h; | |
96% | With [(IPr)PdI]2; Cs2CO3 In ethanol; toluene at 40℃; for 4h; Sealed tube; Inert atmosphere; | |
95% | With Cs2CO3 In toluene at 80℃; for 18h; | |
95% | With potassium fluoride In tetrahydrofuran at 150℃; for 1h; Irradiation; | |
95% | With tripotassium phosphate tribasic; 4-dicyclohexylphosphino-12-(2',6'-dimethoxy)phenyl-[2.2]paracyclophane; palladium diacetate In 1,4-dioxane at 80℃; for 12h; Inert atmosphere; | |
95% | With [PdCl[(η5-C5H5)]Fe[(η5-C5H3)-N2C4H2-Cl](DCPAB)]; potassium-t-butoxide at 120℃; for 12h; | |
95% | With C35H50I2N2O2PPd; Cs2CO3 In 1,4-dioxane at 110℃; for 12h; Inert atmosphere; | |
95% | With anhydrous sodium carbonate In ethanol; lithium hydroxide monohydrate at 20℃; Green chemistry; | |
95% | With di-tert-butyl(2,2-diphenyl-1-methyl-1-cyclopropyl)phosphine; PdCl(π-allyl)(cyclohexyl-(1-methyl-2,2-diphenylcyclopropylphophine)); potassium carbonate In tetrahydrofuran; toluene at 80℃; for 2h; Inert atmosphere; | |
95% | With potassium carbonate In ethanol; lithium hydroxide monohydrate at 20℃; for 0.5h; Green chemistry; | |
95% | With anhydrous sodium carbonate at 80℃; for 3.5h; | |
94% | With potassium carbonate In lithium hydroxide monohydrate at 80 - 90℃; for 16h; | |
94% | With potassium hydroxide In ethanol; N,N-dimethyl-formamide at 100℃; for 20h; Inert atmosphere; | |
94% | With potassium carbonate In lithium hydroxide monohydrate at 80℃; for 8h; Reflux; | |
94% | With dichloro-[1-(3-methoxybenzyl)-3-(2-methoxyethyl)benz-imidazol-2-ylidene](pyridine)palladium; potassium carbonate In lithium hydroxide monohydrate; isopropanol at 50℃; for 2h; | 4.4 General procedure for Suzuki-Miyaura cross-coupling reaction General procedure: Phenylboronic acid (1.5mmol), aryl chloride (1.0mmol), K2CO3 (2.0mmol), PEPPSI-type palladium-NHC catalyst (0.01mmol, 1mol%) (2a-f) and mixture of isopropanol/water (1:3; v/v) (4mL) were added to a small round bottom flask in air. The mixture was stirred at 50°C for 2h. At the end of the reaction, the cooled solution to room temperature was extracted with a mixture of EtOAc/n-hexane (1:5, v/v). The organic phase was separated and dried over anhydrous MgSO4, the solution passed through the micro silica gel column was concentrated. Product characterizations were performed by GC. The reaction yields were determined by GC based on aryl chloride. |
93% | With sodium hydroxide; tetrabutylammonium bromide In lithium hydroxide monohydrate at 100℃; for 4h; | |
93% | With tripotassium phosphate tribasic; P-[2-(dicyclohexylphosphino)phenyl]-N,N-diethyl-P-phenylphosphinic amide; palladium diacetate In toluene at 60℃; for 24h; Inert atmosphere; | |
93% | With potassium phosphate tribasic trihydrate; C25H27ClN3Pd(1+)*F6P(1-) In N,N-dimethyl acetamide at 100℃; for 3h; | |
93% | With C24H29Cl2N3Pd; potassium hydroxide In lithium hydroxide monohydrate at 100℃; for 24h; Green chemistry; | |
93% | With [palladium(II) 1-(4-N,N’,N’’-trimethylbutylammonium)-4-(2-pyridyl)-1H-1,2,3-triazoledichloride]chloride; tetrabutylammonium bromide; potassium carbonate In lithium hydroxide monohydrate at 120℃; for 5h; | |
92% | With 4-(di-tert-butylphosphino)-N,N-dimethylpiperidinium chloride; anhydrous sodium carbonate In lithium hydroxide monohydrate; acetonitrile at 80℃; for 6h; | |
92% | With Cl- P(t-Bu)3CH(CH2CH2)2NMe2+; anhydrous sodium carbonate In lithium hydroxide monohydrate; acetonitrile at 80℃; for 3h; | |
92% | With tripotassium phosphate tribasic; Pd (sulfur-containing palladacycle); tetra(n-tert-butyl)ammonium bromide In N,N-dimethyl-formamide at 25℃; for 16h; | |
92% | With tetrabutylammonium bromide; potassium carbonate In lithium hydroxide monohydrate; N,N-dimethyl-formamide at 130℃; for 6h; | |
92% | With C22H34O; potassium carbonate; palladium (II) chloride In lithium hydroxide monohydrate; N,N-dimethyl-formamide at 90℃; for 4h; | |
92% | With 2C2H4O2*C40H36N2O2Pd; potassium carbonate In N,N-dimethyl-formamide at 100℃; for 6h; | 4.3.2. General procedures of aryl chlorides General procedure: To a flask were added with complex 3 (3.4 mg, 0.005 mmol, 0.5 mol %), phenyl boronic acid (182.9 mg, 1.5 mmol), K2CO3 (276.4 mg, 2.0 mmol), aryl chloride (1.0 mmol), and DMF (3.0 mL). Unless the otherwise note, the reaction mixture was stirred at 100 °C for 6 h. After the completion of the reaction it was cooled to room temperature. The reaction mixture was dissolved in H2O, and extracted with ethyl acetate (3×5.0 mL). The organic layer was collected and dried by Na2SO4, then concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give the desired product. |
92% | With C25H29N3; potassium carbonate; palladium (II) chloride In lithium hydroxide monohydrate; N,N-dimethyl-formamide at 110℃; for 4h; | |
92% | With potassium carbonate In lithium hydroxide monohydrate at 100℃; for 0.916667h; | |
92% | With potassium carbonate at 50℃; for 2.33333h; | General procedure for the Suzuki reaction General procedure: A mixture of aryl halide (1 mmol), phenylboronic acid (1 mmol) or sodium tetraphenyl borate (0.5 mmol), K2CO3 (3 mmol), and Pd-SMU-MNPs (0.006 g, 0.92 mol %) was added to a reaction vessel. The resulting mixture was stirred in H2O or PEG-400 at 50 °C and the progress of the reaction was monitored by TLC. After completion of the reaction, the catalyst was separated by an external magnet and washed with ethylacetate. The reaction mixture was extracted with H2O and ethylacetate and the organic layer was dried over anhydrous Na2SO4 (1.5 g). Then the solvent was evaporated and pure biphenyl derivatives were obtained in good to excellent yields. |
92% | With potassium carbonate In ethanol; lithium hydroxide monohydrate at 80℃; for 2h; Green chemistry; | |
92% | With Cs2CO3 In lithium hydroxide monohydrate at 100℃; for 1.41667h; Green chemistry; | 2.3. General procedure for the preparation of biphenyl products inpresence of [Fe 3 O 4 H 2 L-Pd(0)] as Nanocatalyst General procedure: In the typical procedure, aryl halide (1 mmol) and phenyl-boronic acid (1.2 mmol) were taken in a round-bottom flascontaining 3 mL water. Besides, 3 mmol of Cs 2 CObase and23[Fe 3 O 4 H 2 L-Pd(0)] nanocatalyst (0.8 mol %) were added to the re-342action. The mixture was stirred for appropriate time at reflux con-°ditions (100 °C). The reaction was monitored by TLC. Afterwards,the catalyst was recovered through the magnetic decantation and,×20then, the reaction mixture was extracted with 3mL waterand ethyl acetate. Moreover, the extract was dried over anhydroussodium sulphate. Additionally, the crude product was purified us-ing preparative TLC plates (Silica gel) in n -hexane in order to givethe corresponding products. |
91% | With potassium carbonate In lithium hydroxide monohydrate at 80℃; for 25h; | |
91% | With potassium carbonate In ethanol; lithium hydroxide monohydrate at 50℃; for 3h; Inert atmosphere; | |
91% | With [Pd(3-benzyl-1-(pyrimidin-2-yl)imidazolylidene)2(CH3CN)](PF6)2; Cs2CO3 In lithium hydroxide monohydrate; N,N-dimethyl-formamide at 80℃; for 6h; Inert atmosphere; | |
91% | With C21H28N2; potassium carbonate; palladium (II) chloride In lithium hydroxide monohydrate; N,N-dimethyl-formamide at 110℃; for 2h; | 2.3 General procedure for Suzuki-Miyaura reaction General procedure: In a round bottle, ligand or palladium complexes (1 mol% mmol), aryl halides (1.0 mmol), arylboronic acid (1.2 mmol), K2CO3 (2.0 mmol) and 4 mL of DMF and 1 mL of H2O were added with a magnetic stir bar. The reaction mixture was carried out at the described temperature for the required time, and then the solvent was removed under reduced pressure. The residual was diluted with Et2O (5 mL), followed by extraction twice (2 × 5mL) with Et2O. The organic layer was dried with anhydrous MgSO4, filtered and evaporated under vacuum. The crude products were purified by silica-gel column chromatography using petroleum ether-ethyl acetate (20/1) as an eluent, and the isolated yield was then calculated based on the feeding of the aryl halide. The isolated corresponding products were characterized by 1H NMR and 13C NMR. |
91% | With ϖ-allylpalladium (II) chloride dimer; N,N,N',N'-tetra(diphenylphosphinomethyl)benzene-1,3-diamine; potassium carbonate In N,N-dimethyl acetamide at 130℃; for 40h; Inert atmosphere; Schlenk technique; | |
91% | With anhydrous sodium carbonate In ethanol at 70℃; for 2.66667h; Sealed tube; | |
91% | With C34H25BrClN2OPPd; potassium carbonate In methanol at 80℃; for 2h; Inert atmosphere; | 2.4. General procedure for coupling reactions of aryl halides with boronic acid(Suzuki coupling reaction) General procedure: In a two-necked flask under an atmosphere of nitrogen was placed palladium complexes(1-5) (1mol%), bromobenzene (0.5 mmol), aryl boronic acid (0.75 mmol) andK2CO3 (1 mmol). The mixture was then refluxed at 80 °C for 2 h. The progress of thereaction was monitored by TLC. After completion of the reaction, the solvent wasremoved under reduced pressure and the resulting product was diluted with water(10 ml) and Et2O (10 ml), followed by extraction twice (2x6ml) with Et2O. The combinedorganic fraction was dried over MgSO4. The crude product was purified by columnchromatography by using hexane as eluent. |
91% | With tripotassium phosphate tribasic; Ni(1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene)[P(OPh)3]2 In tetrahydrofuran at 70℃; for 18h; Sealed tube; | |
91% | With anhydrous sodium carbonate In lithium hydroxide monohydrate for 1.58333h; Reflux; Green chemistry; | |
91% | With [(κ2-C6H4CH2NH2)Pd(κ2-bis (diphenylphosphino) methane oxide)](ClO4); anhydrous sodium carbonate at 100℃; for 0.5h; | 2.5 General procedure for Suzuki cross-coupling reaction General procedure: In a typical procedure, a mixture of aryl halide (0.75mmol), phenylboronic acid (1mmol), Na2CO3 (1.5mmol), (0.007g, 0.01mol%) of palladacycle complex 3 as catalyst and 2mL PEG (polyethylene glycol) as solvent was heated at 100°C for an appropriate time. The progress of the reaction is followed by thin-layer chromatography (hexane/EtOAc, 80:20). After completion of the reaction, the mixture was cooled down to room temperature. The solvent was removed and water (15mL) was added, followed by extraction with diethyl ether (3×15mL) and the catalyst was regenerated. The combined organic layers were washed with brine (15mL), dried over anhydrous Na2SO4 (1.5g), and filtered. The organic layers were evaporated under reduced pressure and pure biphenyl derivatives were obtained in good to excellent yields. The products were characterized by comparing their spectral and physical data with those of the credible samples. |
90% | With potassium carbonate In xylene at 130℃; for 20h; | |
90% | With tripotassium phosphate tribasic; PS-supported 2'-(dicyclohexylphosphino)-biphenyl-4-COOH In toluene at 100℃; for 20h; | |
90% | With Cs2CO3 In lithium hydroxide monohydrate; acetonitrile at 70℃; for 24h; | |
90% | With potassium carbonate In lithium hydroxide monohydrate; N,N-dimethyl-formamide at 150℃; for 0.5h; microwave irradiation; | |
90% | With potassium phosphate tribasic trihydrate; [(NC5H3(C(CMe)=N-2,6-(i-Pr)2C6H3)2)PdCl]PdCl3 In Aminol at 100℃; for 10h; | |
90% | With palladium diacetate; potassium carbonate In ethanol; N,N-dimethyl acetamide at 80℃; for 0.75h; | |
90% | With 1,3-bis(2,6-diisopropylphenyl)-1,3,2-diazaphospholidine-2-oxide; tripotassium phosphate tribasic; Ni(PPh<SUB>3</SUB>)<SUB>2</SUB>(1-naphthyl)Cl In toluene at 110℃; for 18h; Schlenk technique; Inert atmosphere; | General procedure for the Suzuki cross-coupling reactions General procedure: Aryl chloride (1.0 mmol),arylboronic acid (1.2 mmol), precatalyst (0.05 mmol), preligand (0.05 mmol),and base (3.0 mmol) were added to a Schlenk tube equipped with a magnetic stirring bar, a septum, and a reflux condenser. After the tube was evacuated and refilled with nitrogen gas three times, degassed solvent (3 mL) was added via a syringe. The reaction mixture was heated to the described temperature for the required time. After the reaction cooled to room temperature, water (10 mL) was added tothe reaction mixture. The resulting mixture was extracted with CH2Cl2(3 x 10 mL). The combined organic layers were dried over anhydrous Na2SO4,filtered and concentrated to dryness. The remaining residue was analyzed by GC(Table 1) or purified by flash chromatogram phy on silica gel with ethylacetate-hexanes (0-20% ethyl acetate in hexanes) of as eluents. |
90% | With PdPtZn nanoparticle thin film In lithium hydroxide monohydrate at 80℃; for 1.5h; | |
90% | With C37H33ClFeNPPdS; potassium carbonate In dimethyl sulfoxide at 110℃; for 6h; | |
90% | With potassium carbonate at 100℃; for 3.33333h; Green chemistry; | 2.5. General procedure for the Suzuki coupling reaction General procedure: A mixture of an aryl halide (1 mmol), phenylboronic acid (1mmol), K2CO3 (3 mmol), and Fe3O4MCM-41Pd(0)-P2C(0.004 g, 0.66 mol%) was added to a reaction vessel. The resultingmixture was stirred in PEG-400 at 60 °C and the progressof the reaction was monitored by thin-layer chromatography(TLC). After completion of the reaction, the catalyst wasseparated using an external magnet and washed with ethylacetate. The reaction mixture was extracted with ethyl acetateand water, and the organic layer was dried over anhydrousNa2SO4 (1.5 g). The solvent was evaporated and pure productswere obtained in good to excellent yields. |
90% | With bis[(benzyloxycarbonylmethyl)triphenylphosphonium]hexabromopalladate(II); potassium carbonate at 80℃; for 1.08333h; | General procedure for Suzuki cross-coupling reaction General procedure: In a typical procedure, a mixture of aryl halide (1 mmol), phenylboronic acid (1 mmol), K2CO3 (1.5 mmol), 0.010 g of [PhCH2COOCH2P(Ph)3]2[Pd2Br6] as catalyst and 2 mL polyethylene glycol (PEG) as solvent were heated at 80 °C and the progress of the reaction was followed by TLC. After completion of the reaction, the mixture was cooled down to room temperature. Water was added to the reaction mixture, filtered to remove the catalyst and extracted three times with diethyl ether. The combined ethyl acetate extracts were dried over anhydrous sodium sulfate, filtered and evaporated to give the pure product. |
90% | With 1-benzyl-4-(2,6-dimethoxyphenyl)-1H-1,2,3-triazole; Palladium(0) bis(dibenzylideneacetone); sodium tertiary butoxide In toluene at 100℃; for 18h; Schlenk technique; Inert atmosphere; | General procedure for the Suzuki coupling reaction of aryl chlorides 4a-4n with phenylboronic acid (5). General procedure: A Schlenk tube fitted with a rubber septum was charged with aryl chloride 4a-4n (1.00 mmol), Pd(dba) 2 (2.5 mol %), PhB(OH) 2 (1.5 mmol, 122 mg), ligand L2 (5 mol %), and sodium tert-butoxide (2.00 mmol, 0.45 g). The mixture was purged three times with argon, freshly distilled toluene (3 mL) was added under argon via a syringe, the rubber septum was replaced with a Teflon cap, and the mixture was stirred in an oil bath at 100°C for 18 h. The progress of the reaction was monitored by TLC until the substrate was completely consumed. After cooling to room tem-perature, 20 mL of ethyl acetate and 20 mL of brine were added, and the mixture was vigorously stirred in a separatory funnel. The organic phase was separated, and the aqueous layer was extracted with ethyl acetate (2 × 10 mL). The extracts were combined with the organic phase, dried over Na 2 SO 4 , filtered, and con-centrated, and the residue was purified by column chromatography on silica gel. |
90% | With 4-(2,6-dimethoxyphenyl)-1-phenyl-1H-1,2,3-triazole; Palladium(0) bis(dibenzylideneacetone); sodium tertiary butoxide In toluene at 100℃; for 18h; Inert atmosphere; Sealed tube; | 2.5. General procedure (C) for suzuki coupling reaction General procedure: In the inert atmosphere of glove box, 4-chlorotoluene(1.00 mmol, 127 mg), Pd(OAc)2 (2.5 mol%), PhB(OH)2 (1.00 mmol,122 mg), ligand (5 mol%), K3PO4 (2.00 mmol, 0.45 g), were weighedinto oven dried micro-vial, fitted with rubber septum and purgedunder argon outside the glove box. Freshly distilled toluene (3 mL)was added under argon to micro-vial via syringe. The septum wasremoved and micro-vial was sealed with Teflon screw cap. Themixture was stirred at 80 °C in oil bath for 12 h. Reaction progresswas monitored by TLC until substrate was completely consumed.After cooling to rt, and diluting with EtOAc (20 mL), the mixturewas washed with brine solution (20 mL). The aq. layer wasextracted with EtOAc (20 mL) and the combined organic layerswere dried over anhydrous Na2SO4, filtered, and concentrated. Thematerial was then purified by chromatography on silica gel. |
90.4% | With tripotassium phosphate tribasic; tetrabutylammonium bromide In lithium hydroxide monohydrate at 100℃; for 5h; Microwave irradiation; Green chemistry; | |
89% | With anhydrous sodium carbonate In ethanol; lithium hydroxide monohydrate; toluene at 80℃; for 20h; | |
89% | With potassium carbonate In N,N-dimethyl-formamide at 130℃; for 36h; | 4.6. General procedure for the Suzuki coupling of aryl chlorides and phenylboronic acid General procedure: A mixture of aryl chloride (1 mmol), phenylboronic acid (1.2 mmol), K2CO3 (2.0 mmol), DMF (5.0 mL), and the solid catalyst was charged in a 25 mL round-bottom flask and stirred at 130 °C. The end of reaction was tracked by TLC, the catalyst was separated with a magnet and washed with diethyl ether (2×10 mL), deionized water (2×10 mL), and then dried under vacuum for the next run. The aqueous phase was extracted with diethyl ether (2×15 mL) and the combined organic phases were concentrated. These crude products were further purified by recrystallization. |
89% | With potassium carbonate at 80℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94.8% | With bis(triphenylphosphine)nickel(II) chloride; zinc(II) chloride In tetrahydrofuran at 0 - 5℃; for 8h; Inert atmosphere; | 13.2 Example 1 Preparation Step 2 4- cyanobiphenyl In another four 1L reaction flask, a nitrogen atmosphere, followed by adding 219.54g of tetrahydrofuran,73.18g (0.532mol) of chlorobenzonitrile, 0.73g (0.00532mol) zinc chloride, 0.35g (0.000532mol)Bis (triphenylphosphine) nickel (II) dichloride, open mixing, cooling to 0 ~ 5 the reaction system, and a solution of 1. The generated Grignard reagent phenyl magnesium chloride to the system, maintaining the temperature at 0 ~ 5 , dropwise for 3 hours,After addition was complete, heat 5h, sampling to detect completion of the reaction, the solution of dilute hydrochloric acid to the reaction mixture to quench the reaction,Stirred for 10min, allowed to stand, stratification, the organic layer was washed with 5% sodium chloride solution, allowed to stand for separation, the organicLayer was added activated carbon, heated to reflux, filtered hot and the filtrate was concentrated under reduced pressure is not off to a tetrahydrofuran. Stop, cooling to 20 ~ 25 , to give a white flaky solid, as a 4-cyanobiphenyl, was solid weighed 90.4g,Yield 94.8% (in terms of chlorobenzene nitrile), purity (GC) ≥99.0%. |
93% | With [{C4H2N-2,5-(CH2PPh2)2-κ3PNP}NiCl] In tetrahydrofuran; toluene at 23℃; for 6h; Inert atmosphere; Schlenk technique; | |
93.4% | With bis(triphenylphosphine)nickel(II) chloride; zinc(II) chloride In tetrahydrofuran at 10 - 15℃; for 7h; Inert atmosphere; |
88% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; zinc(II) chloride In tetrahydrofuran; dichloromethane at 55 - 60℃; | |
With [Ni(9,10-phenanthrenequinonethiosemicarbazone)2] In diethyl ether at 20℃; for 4h; | 2.4a Kumada-Corriu reaction: General procedure: Aryl halide (10 mmol) was added to catalyst (0.2 mol%) in 5 mL diethyl ether. Phenylmagnesium chloride (10 mmol) was then added dropwise and the reaction mixture was stirred for 4 h at room temperature. Then the reaction was ended by addition of water. The mixture was extracted with ethyl acetate and the obtained organic layer was dried over MgSO4. The crude mixture was analyzed by gas chromatography and then purified by column chromatography on silica gel to afford the desired product. The conversion percentage was determined against the remaining aryl halide. In addition, the isolated product was characterized by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With tBu2P-N=P(iBuPCH2CH2)3N; tetrabutyl ammonium fluoride; palladium diacetate In 1,4-dioxane at 80℃; for 2h; Inert atmosphere; | |
92% | With potassium carbonate In ethylene glycol at 100℃; for 1.16667h; Inert atmosphere; | |
90% | With C58H78Cl4N6Pd2; tetrabutyl ammonium fluoride In toluene at 120℃; for 5h; |
90% | With [PdCl2(N,N’-bis-(2,4,6-trimethylphenyl)imidazol-2-ylidene)]2(μ-(1,2-bis(diphenylphosphino)ethane)); tetrabutyl ammonium fluoride In toluene at 120℃; for 6h; Microwave irradiation; | |
89% | With NHC-Pd(II)-Im; tetrabutyl ammonium fluoride In toluene at 120℃; for 3h; Inert atmosphere; | 2.2. General procedure for the NHC-Pd(II)-Im complex 1 catalyzed Hiyama reaction of aryl chlorides with aryltrimethoxysilanes General procedure: Under N2 atmosphere, NHC-Pd(II)-Im 1 (1.0 mol%), dry toluene (2.0 mL), aryl chlorides 2 (0.81 mmol), aryltrimethoxysilanes 3 (2.0 equiv) and TBAF•3H2O (2.0 equiv) were successively added into a Schlenk reaction tube. Then the tube was placed in a 120 °C oil bath and stirred for 3 h. The mixture was then allowed to cool to room temperature, diluted with ethyl acetate and washed with brine, dried over anhydrous Na2SO4, concentrated in vacuo and then purified by flash chromatography to give the pure products 4. |
88% | With 3-(dicyclohexylphosphino)-2-(2-methoxyphenyl)-1-methyl-1-H-indole; tetrabutyl ammonium fluoride; palladium diacetate In toluene at 110℃; for 3h; Schlenk technique; Inert atmosphere; Sealed tube; | |
80% | With 1-(2-pyrimidyl)-3-(2,4,6-trimethylphenyl)imidazoline-2-ylidene palldium(II) dichloride; tetrabutyl ammonium fluoride; caesium carbonate In 1,4-dioxane at 80℃; for 6h; Inert atmosphere; | |
76% | With 1-butyl-3-methyl-3H-imidazol-1-ium fluoride In acetonitrile at 70℃; for 8h; Inert atmosphere; | |
100 % Chromat. | With palladium diacetate; N,N′-bis(2,6-diisopropylphenyl)imidazol-2-ylidene hydrochloride; tetrabutyl ammonium fluoride In 1,4-dioxane at 80℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With potassium phosphate; (NC5H3(N2C7H4(CH2)3CH3)2)NiBr(1+)*Br(1-)=Ni(NC5H3(N2C7H4(CH2)3CH3)2)Br2; triphenylphosphine In 1,4-dioxane at 100℃; for 24h; | |
99% | With trans-chloro(1-naphthyl)bis-(triphenylphosphine)nickel(II); tricyclohexylphosphine tetrafluoroborate; potassium carbonate In water; toluene at 20℃; for 24h; Inert atmosphere; | |
97% | With 1,1'-bis-(diphenylphosphino)ferrocene; (9-phenanthrenyl)Ni(II)(PPh3)2Cl; potassium carbonate In toluene at 110℃; for 15h; Inert atmosphere; | 4-Cyano-1,1'-biphenyl (4l) General procedure: 4.2 General procedure for the Suzuki cross-coupling reactions. Aryl tosylate (1.0 mmol), arylboronic acid (1.2 mmol), precatalyst 1 (0.05 mmol), ligand (0.05 mmol) and base (3.0 mmol) were added to a Schlenk tube equipped with a magnetic stirring bar, a septum and a reflux condenser. After the tube was evacuated and refilled with nitrogen gas three times, degassed solvent (3 mL) was added via a syringe. The reaction mixture was heated to the described temperature for the required time. After the reaction cooled to room temperature, water (10 mL) was added to the reaction mixture. The resulting mixture was extracted with CH2Cl2 (3×10 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated to dryness. The remaining residue was analyzed by GC (Table 1) or purified by flash chromatography on silica gel with ethyl acetate-hexanes (0-20% ethyl acetate in hexanes) of as eluents (Tables 2 and 3). |
95% | With potassium phosphate; bis(tricyclohexylphosphine)nickel(II) dichloride; tricyclohexylphosphine In 1,4-dioxane at 130℃; | |
95% | With potassium phosphate; BF4(1-)*C31H33ClN5Ni(1+) In 1,2-dimethoxyethane at 120℃; for 24h; Inert atmosphere; Sealed tube; | |
89% | With potassium phosphate; Ni(1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene)[P(OPh)3]2 In tetrahydrofuran at 70℃; for 18h; Sealed tube; | |
87% | With potassium phosphate; [(N,N,N',N'-tetramethylethylendiamine)NiCl(o-tolyl)]; tricyclohexylphosphine In 1,4-dioxane at 130℃; for 14h; Glovebox; Inert atmosphere; Sealed tube; | |
40% | Stage #1: p-cyanophenyl p-toluenesulfonate; phenylboronic acid With 1,1'-bis-(diphenylphosphino)ferrocene; potassium phosphate; C76H70FeNiO6P4 In 1,4-dioxane at 100℃; for 16h; Inert atmosphere; Sealed tube; Stage #2: With dihydrogen peroxide In water at 20℃; for 0.5h; | 4-Phenyl Benzonitrile 23 Method C 4-Tosylbenzonitrile 24 (137 mg, 0.5 mmol), phenylboronic acid (107 mg, 0.600 mmol), (dppf)Ni[P(O-p-Tol)3]2 25 (30.6 mg, 0.0250 mmol), DPPF (13.9 mg, 0.0250 mmol), and potassium phosphate (424.3 mg, 2 mmol) were dissolved in 1,4-dioxane (3 mL) and stirred in a sealed vessel at 100 C under nitrogen for 16 h. The reaction was cooled to RT and water wasa dded (3 mL). The aqueous layer was extracted with dichloromethane (35 mL) and the combined organic layers were washed with water (25 mL) and dried over MgSO4. Afterfiltration, the solvent was removed under reduced pressure togive a yellow-brown oil, which was subjected to columnchromatography (hexanes/EtOAc 100 : 0 - 97 : 3) to afford ayellow solid, which was then stirred with H2O2 (3mL of a 30%w/w aqueous solution) for 30 min. The mixture was extractedwith ethyl acetate (23 mL), dried over MgSO4, and filteredthrough a plug of silica to afford 4-phenyl benzonitrile 23 as awhite solid (35.9 mg, 40 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(ll) dichloride; triphenylphosphine; cesium fluoride; In N,N-dimethyl-formamide; at 90℃; for 1h;Inert atmosphere; Green chemistry; | General procedure: Under inert atmosphere (N2), in a 25 mL round bottom flask, Ar3Bi (0.208 mmol; 0.35 eq.), CsF (0.24 g: 1.8 mmol; 3 eq.), PPh3 (0.004 g: 0.018 mmol; 3 mol%), the aryl bromide (0.60 mmol; 1 eq.) was added to DMF (5 mL). The solution was warmed to 90 C prior addition of PEPPSI IPr (0.012 g: 0.018 mmol; 3 mol%). The reaction was monitored by GC/MS to follow the total consumption of the aryl bromide. Cooled to room temperature (RT), the reaction mixture was diluted by addition of diethyl ether (20 mL) and aqueous HCl 6 M (30 mL). After decantation, the aqueous solution was extracted with diethylether (2 * 20 mL). The collected organic phases were then washed with HCl 6 N (2 * 25 mL), water (25 mL) and brine (25 mL) prior drying over MgSO4. After concentration under reduced pressure, the resulting crude product was subjected to purification by column chromatography leading after concentration under reduced pressure to the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | Stage #1: ethanol; 4-cyano-1,1'-biphenyl With ammonia In chloroform at 0℃; for 2h; Inert atmosphere; Stage #2: With hydrogenchloride In chloroform at 20℃; for 12h; | 5 Ethyl 4-biphenylylimidate hydrochloride [Chemical Formula (1-10a)] was produced by the following method. Chloroform (250 mL) and ethanol (80 mL) were added to 4-cyanobiphenyl (25.3 g, 140 mmol) under an argon atmosphere. The solution was cooled to 0° C. and stirred for 2 hours while passing hydrogen chloride gas, then the hydrochloric acid gas was stopped, the reaction mixture was allowed to reach room temperature and stirred for another 12 hours. After the reaction, low boiling substances were distilled off from the reaction mixture under reduced pressure, diethyl ether was added to the obtained solid, and the solid was filtered off. The solid was washed with diethyl ether then hexane. The obtained solid was dried under reduced pressure to give ethyl 4-biphenylylimidate hydrochloride as a white solid (32 g, 87%). |
72% | With hydrogenchloride In ethyl acetate at 20℃; for 24h; | |
With hydrogenchloride at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | Stage #1: diallyldiphenylsilane With tetrabutyl ammonium fluoride In tetrahydrofuran; water at 20℃; for 1h; Stage #2: 4-Cyanochlorobenzene With XPhos In tetrahydrofuran; water at 80℃; for 5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With potassium phosphate; C58H72N2O4P2Pd2 In <i>tert</i>-butyl alcohol at 110℃; for 3h; Inert atmosphere; | |
92% | With potassium phosphate; 1,2-bis(diphenylphosphino)ethane nickel(II) chloride; ethyl-diphenyl-phosphane In toluene at 80℃; for 14h; | |
92% | With potassium phosphate; 2-[2-(dicyclohexylphosphino)-phenyl]-1-methyl-1H-indole; palladium diacetate In <i>tert</i>-butyl alcohol at 110℃; for 17h; Inert atmosphere; |
91% | With potassium phosphate; (NC5H3(N2C7H4(CH2)3CH3)2)NiBr(1+)*Br(1-)=Ni(NC5H3(N2C7H4(CH2)3CH3)2)Br2; triphenylphosphine In 1,4-dioxane at 100℃; for 24h; | |
63% | With potassium phosphate; BF4(1-)*C31H33ClN5Ni(1+) In 1,4-dioxane at 120℃; for 24h; Inert atmosphere; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With N-cyclohexyl-1-[2-(diphenylphosphanyl)phenyl]methanimine; potassium carbonate; palladium dichloride In water; dimethyl sulfoxide at 50℃; for 7h; | |
97% | With potassium carbonate In water; dimethyl sulfoxide at 50℃; for 7h; | 5 Example 5; Method for Preparing Organic Compounds by Using Silicon-Based Cross-Coupling Reagents 2a to 2d of the Present Invention; Any one of the silicon-based cross-coupling reagents 2a to 2d of the present invention was used to carry out cross-coupling reaction with an organic halide I-R10, thereby producing various kinds of organic compounds. Table 2 shows reaction times, yields, the silicon-based cross-coupling reagent R1 used and R10 of an organic halide I-R10. Note that, in Table 2, products are numbered to correspond to numbers of the following substances respectively.; An aryl iodide (0.7 mmol) and water (25 mg, 1.4 mmol) were sequentially added to a mixture of an arylsilane (0.81 mmol), K2CO3 (194 mg, 1.4 mmol), N-(2-diphenylphosphinobenzyliden)cyclohexylamine (10.4 mg, 28 μmol), and PdCl2 (3.7 mg, 21 μmol) in DMSO (4.0 mL), and the resulting mixture was stirred at 50° C. When each of the times shown in Table 2 had passed, the resulting mixture was diluted with diethyl ether and was washed with water and brine, and then was dried over anhydrous MgSO4. After concentration under reduced pressure, the residue was purified by flash chromatography on silica gel to obtain organic compounds p31 to p50 which were cross-coupling products respectively corresponding to yields shown in Table 2. The following shows chemical formulas and analysis data of the resultant organic compounds p36, p37, and p38. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | Stage #1: phenyllithium With 3-(1,1-diethyl-1,3-dihydrobenzo[c][1,2]oxasilol-3-yl)pyridine In diethyl ether at 20℃; for 2h; Stage #2: 4-iodobenzonitrile With copper(l) iodide; palladium dichloride In tetrahydrofuran; diethyl ether at 20℃; for 2h; | |
92% | Stage #1: phenyllithium With 3-butyl-1,1-dimethyl-1,3-dihydro-benzo[c][1,2]oxasilole In tetrahydrofuran; dibutyl ether at -78 - 20℃; for 1h; Inert atmosphere; Stage #2: 4-iodobenzonitrile With copper(l) iodide; N-cyclohexyl-1-[2-(diphenylphosphanyl)phenyl]methanimine; palladium dichloride In tetrahydrofuran; dibutyl ether at 20℃; for 2h; Inert atmosphere; | |
92% | Stage #1: phenyllithium With 3-butyl-1,1-dimethyl-1,3-dihydro-benzo[c][1,2]oxasilole In tetrahydrofuran at -78 - 20℃; for 1h; Stage #2: 4-iodobenzonitrile With copper(l) iodide; N-cyclohexyl-1-[2-(diphenylphosphanyl)phenyl]methanimine; palladium dichloride In tetrahydrofuran at 20℃; for 2h; Inert atmosphere; |
92% | Stage #1: phenyllithium In tetrahydrofuran at -78 - 20℃; Inert atmosphere; Stage #2: 4-iodobenzonitrile With copper(l) iodide; palladium dichloride In tetrahydrofuran at 20℃; for 18h; Inert atmosphere; | |
92% | Stage #1: phenyllithium In tetrahydrofuran at -78 - 20℃; for 3h; Stage #2: 4-iodobenzonitrile With copper(l) iodide; N-cyclohexyl-1-[2-(diphenylphosphanyl)phenyl]methanimine; palladium dichloride In tetrahydrofuran at 20℃; for 18h; | |
91% | Stage #1: phenyllithium In tetrahydrofuran; dibutyl ether at -78 - 20℃; for 3h; Inert atmosphere; Stage #2: 4-iodobenzonitrile With copper(l) iodide; palladium dichloride In tetrahydrofuran; dibutyl ether at 20℃; for 2h; Inert atmosphere; | |
91% | Stage #1: phenyllithium In tetrahydrofuran; dibutyl ether at -78 - 20℃; for 3h; Stage #2: 4-iodobenzonitrile With copper(l) iodide; N-cyclohexyl-1-[2-(diphenylphosphanyl)phenyl]methanimine; palladium dichloride In tetrahydrofuran; dibutyl ether at 20℃; for 2h; | 37 To a cooled solution of siloxane polymer in THF (0.193 g, 0.752 mmol, 3.0 equiv, 10 mg/mL) at -78°C was added PhLi in Bu20 (348 tL, 1.8 M, 0.627 mmol, 2.5 equiv) dropwise. The reaction mixture was allowed to warm to rt and was stirred for 3 h, and a white, cloudy solution developed. A solid mixture of PdC12 (1.3 mg, 7.5 .imol, 0.03 equiv), CuT (4.8 mg, 0.025 mmol, 0.1 equiv), and dpca (3.7 mg, 0.01 mmol, 0.04 equiv) was combined and added to the reaction flask, followed by addition of 4-iodobenzonitrile (56.8 g, 0.248 mmol, 1.0 equiv). The obtained reaction mixture was stirred vigorously at rt. Care should be taken so that all reactants are submerged in THF and no solid is deposited on the side of the flask. After 2 h, the reaction mixture was quenched with sat. aq. NH4C1 (5 mL), followed by addition of d.i. H20 (5 mL). The organic layer was collected and the aqueous layer was extracted with Et20 (2 x 10 mL). The combined organic layers were washed with brine, dried with MgSO4, and concentrated in vacuo to 1-2 mL in volume. The obtained concentrated solution was added dropwise into a vigorously stirred solution of CH3CN (250 mL). The precipitated polymer was filtered and the supernatant was concentrated in vacuo to provide the crude product. Following removal from the supernatant, the polymer was re-dissolved in DCM (20 mL) and filter through a glass fritted funnel to remove insoluble particles, if there is any. The obtained solution was then concentrated in vacuo to provide the recovered polymer (192 mg, 99 % recovery). The crude product was purified by chromatography on Si02 (2 % Et20/ hexanes) to afford 4-cyanobiphenyl (40.3 mg, 0.225 mmol, 91 %) as a colorless solid. |
87% | Stage #1: phenyllithium In tetrahydrofuran; dibutyl ether at 0 - 20℃; for 0.5h; Stage #2: 4-iodobenzonitrile With copper(l) iodide In tetrahydrofuran; dibutyl ether; N,N-dimethyl-formamide at 80℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With palladium diacetate; caesium carbonate In methanol; toluene at 60℃; for 6h; | General procedure for Suzuki coupling: General procedure: Preparation of biphenyl-4-carbonitrile (38): Pd(OAc)2 (2.3 mg, 1 mmol %), 4-bromo-benzonitrile (37) (182 mg, 1.0 mmol), 4,4,6-trimethyl-2-phenyl-[1,3,2] dioxaborinane (26) (224.4 mg, 1.1 mmol), Cs2CO3 (650 mg, 2 mmol), toluene (4 mL)-methanol (1 mL) were mixed together in a small reaction tube and the mixture was heated at 60 °C. The reaction progress was followed by TLC (15% ethyl acetate:hexanes). After the starting materials were consumed the mixture was cooled and filtered through celite followed by washing with toluene. The solvent was evaporated under reduced pressure and the residue was purified by flash chromatography on silica gel (15% ethyl acetate:hexanes) to obtain the title compound in 95% yield. 1H NMR (400 MHz, CDCl3): δ 7.74-7.67 (m, 4H), 7.62-7.58 (m, 2H), 7.53-7.41 (m, 3H). 13C NMR (100.6 MHz, CDCl3): δ 145.9, 139.4, 133.7, 132.9, 132.8, 129.4, 128.9, 128.0, 127.5, 119.2, 111.1 |
95% | With caesium carbonate In methanol; toluene at 60℃; | Synthesis of biphenyl-4-carbonitrile Synthesis of biphenyl-4-carbonitrile Pd(OAc)2 (2.3 mg, 1 mmol %), 4-bromo-benzonitrile (182 mg, 1.0 mmol), 4,4,6-trimethyl-2-phenyl-[1,3,2]dioxaborinane (224.4 mg, 1.1 mmol), Cs2CO3 (650 mg, 2 mmol), toluene (4 mL)-methanol (1 mL) were mixed together in a small reaction tube and the mixture was heated at 60° C. The reaction progress was followed by TLC (15% ethyl acetate:hexanes). After the starting materials were consumed the mixture was cooled and filtered through Celite followed by washing with toluene. The solvent was evaporated under reduced pressure and the residue was purified by flash chromatography on silica gel (15% ethyl acetate:hexanes) to obtain the title compound in excellent yield (95%). 1H NMR (400 MHz, CDCl3): δ 7.74-7.67 (m, 4H), 7.62-7.58 (m, 2H), 7.53-7.41 (m, 3H). 13C NMR (100.6 MHz, CDCl3): δ 145.9, 139.4, 133.7, 132.9, 132.8, 129.4, 128.9, 128.0, 127.5, 119.2, 111.1. |
97 % Chromat. | With potassium phosphate In N,N-dimethyl-formamide at 100℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With potassium carbonate; In 1-methyl-pyrrolidin-2-one; at 110℃; for 5h;Schlenk technique; Inert atmosphere; Green chemistry; | General procedure: An oven-dried Schlenk tuble equipped with a magnetic stirring bar was charged with MCM-41-N,N-Pd(OAc)2 (49 mg, 0.02 mmol Pd), aryl iodide (3.2 mmol), triarylbismuth (1.0 mmol), and K2CO3 (4.0 mmol) followed by anhydrous NMP (3 mL) under Ar. The reaction mixture was stirred in an oil bath at 110 C for 5-24 h. The reaction mixture was cooled to room temperature and filtered. The MCM-41-N,N-Pd(OAc)2 complex was washed with distilled water (2×5 mL), NMP (2×5 mL) and Et2O (2×5 mL) and reused in the next run. The filtrate was quenched with water, and extracted with ethyl acetate (2×30 mL). The combined ethyl acetate extract was washed with dilute hydrochloric acid (10 mL), saturated sodium bicarbonate solution (10 mL), brine (2×10 mL), and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was purified by flash column chromatography on silica gel. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38% | General procedure: Under nitrogen condition, potassium tert-butoxide (2.25 g, 0.02 mol) was dissolved in150 mL of tert-amyl alcohol for 15 min and the mixture was heated to 110. Iron(III) chloride (s.a) was added and stirred for 30 min then 4-chlorobenzonitrile (1.5 g, 0.01 mol) was added and stirred for 1 hr at the same temperature. Diisopropyl succinate (1.01g, 0.005 mol) was dissolved in 30 mL of tert-amyl alcohol and dropwised to the mixture for 3 hr. Then 60 mL of water was poured into mixture and stirred for 20 hr at the same temperature. After reaction, the mixture was cooled to room temperature. The mixture was filtered off and washed by water, methanol. The red pigment was purified by 50 mL methanol and stirred for 30 min at 60. After stirring, the solution was filtered off and dried under vacuum to obtain Pigment . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
159 mg (89%) | With potassium fluoride;palladium diacetate; In tetrahydrofuran; | EXAMPLE 32 Synthesis of 4-cyanobiphenyl An oven dried resealable Schlenk tube was evacuated and backfilled with argon and charged with palladium acetate (2.2 mg, 0.01 mmol, 1.0 mol percent), 2-(di-tert-butylphosphino)biphenyl (6.0 mg, 0.020 mmol, 2.0 mol percent), phenylboronic acid (183 mg, 1.5 mmol), potassium fluoride (174 mg, 3.0 mmol), and 4-chlorobenzonitrile (136 mg, 1.0 mmol). The tube was evacuated and backfilled with argon, and THF (1 mL) was added through a rubber septum. The tube was sealed with a teflon screwcap, and the reaction mixture was stirred at room temperature until the starting aryl chloride had been completely consumed as judged by GC analysis. The reaction mixture was then diluted with ether (30 mL) and poured into a separatory funnel. The mixture was washed with water (20 mL), and the aqueous layer was extracted with ether (20 mL). The combined organic layers were washed with brine (20 ml), dried over anhydrous magnesium sulfate, filtered, and concentrated. The crude material was purified by flash chromatography on silica gel to afford 159 mg (89percent) of the title compound. |
159 mg (89%) | With potassium fluoride;palladium diacetate; In tetrahydrofuran; | Example 32 Synthesis of 4-cyanobiphenyl An oven dried resealable Schlenk tube was evacuated and backfilled with argon and charged with palladium acetate (2.2 mg, 0.01 mmol, 1.0 mol percent), 2-(di-tert-butylphosphino)biphenyl (6.0 mg, 0.020 mmol, 2.0 mol percent), phenylboronic acid (183 mg, 1.5 mmol), potassium fluoride (174 mg, 3.0 mmol), and 4-chlorobenzonitrile (136 mg, 1.0 mmol). The tube was evacuated and backfilled with argon, and THF (1 mL) was added through a rubber septum. The tube was sealed with a teflon screwcap, and the reaction mixture was stirred at room temperature until the starting aryl chloride had been completely consumed as judged by GC analysis. The reaction mixture was then diluted with ether (30 mL) and poured into a separatory funnel. The mixture was washed with water (20 mL), and the aqueous layer was extracted with ether (20 mL). The combined organic layers were washed with brine (20 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated. The crude material was purified by flash chromatography on silica gel to afford 159 mg (89percent) of the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With [bis(2-methylallyl)cycloocta-1,5-diene]ruthenium(II); potassium <i>tert</i>-butylate; hydrogen bromide; hydrogen; 2-((di-iso-propylphosphino)methyl)-1-methyl-1H-imidazole In tetrahydrofuran; water; acetone; toluene at 20℃; for 5.5h; Inert atmosphere; Schlenk technique; Autoclave; | |
98% | With hydrogen; acetic acid at 20℃; for 1h; Sealed tube; chemoselective reaction; | |
98% | With lithium aluminium tetrahydride In tetrahydrofuran at 40 - 70℃; for 4h; | 4.4. Procedure for transformation of 4-cyanobiphenyl 2a into 4-(Aminomethyl)biphenyl 3a To a solution of 4-cyanobiphenyl 2a (1.0 mmol, 179.2 mg) in THF (8.0 mL) were slowly added LiAlH4 (1.5 mmol, 56.9 mg) at 0 °C. The obtained mixture was stirred for 4 h at 70 °C. Water (5 mL) and aq. NaOH 1M, (10.0 mL) were added to the reaction mixture. The aqueous layer was extracted with CHCl3 (5.0 mL x 3). The organic layer was washed with brine, dried over Na2SO4, and filtered through celite. The solvent was removed under reduced pressure to give 4-(aminomethyl)biphenyl 3a (179.6 mg, 98%). 4.4.1. 4-(Aminomethyl)biphenyl (3a) Yield: 179.6 mg (98%); white solid; Mp 128-129 °C: IR (neat) 3269 (br), 2630, 1586, 1485, 1396, 1304, 1245, 1131, 986 cm-1; 1H NMR (400 MHz, CDCl3): δ = 3.93 (s, 2H), 7.34 (t, 1H, J = 7.4 Hz), 7.39 (d, 2H, J = 8.2 Hz), 7.44 (dd, 2H, J = 7.7, 7.4 Hz), 7.57-7.61 (m, 4H); 13C{1H}NMR (100 MHz, CDCl3): δ = 46.2, 127.0, 127.2, 127.3, 127.5, 128.7, 139.8, 140.9, 142.4; HRMS (ESI) Calcd for C13H14N [M+H]+ = 184.1121, Found = 184.1120. |
95% | With ammonia; hydrogen In water; isopropyl alcohol at 80℃; for 24h; Autoclave; | |
92% | With ammonia; hydrogen In toluene at 120℃; for 16h; Autoclave; | |
71% | With C46H49CoN3P4(2+)*2BF4(1-); potassium <i>tert</i>-butylate; hydrogen In isopropyl alcohol at 90℃; for 16h; | |
78 %Chromat. | With [bis(2-methylallyl)cycloocta-1,5-diene]ruthenium(II); potassium <i>tert</i>-butylate; hydrogen; N,N'-dimesityl-4,5-dihydro-1H-imidazolium tetrafluoroborate In toluene at 80℃; for 1h; chemoselective reaction; | |
93 %Chromat. | With [bis(2-methylallyl)cycloocta-1,5-diene]ruthenium(II); 1,1'-bis(diphenylphosphino)ferrocene; potassium <i>tert</i>-butylate; hydrogen In toluene at 80℃; for 1h; Inert atmosphere; Autoclave; chemoselective reaction; | |
With hydrogen In carbon dioxide at 50℃; for 4h; chemoselective reaction; | ||
84 %Chromat. | With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; 1,4-di(diphenylphosphino)-butane; iso-butanol; sodium hydroxide at 120℃; for 0.333333h; Inert atmosphere; | |
52 %Chromat. | With formic acid; palladium 10% on activated carbon; triethylamine In tetrahydrofuran at 40℃; for 12h; | |
93 %Chromat. | With Fe-<SUP>Cy</SUP>MACHO; hydrogen In isopropyl alcohol at 70℃; for 3h; Autoclave; chemoselective reaction; | |
99 %Chromat. | With MnBr(CO)2[NH(CH2CH2P(iPr)2)2]; hydrogen; sodium t-butanolate In toluene at 120℃; for 24h; Autoclave; | |
99%Chromat. | With ammonium hydroxide; hydrogen In isopropyl alcohol at 120℃; for 15h; Autoclave; | |
> 99 %Chromat. | With C28H29Cl2CoNP2; hydrogen; sodium methylate In 1,4-dioxane at 80℃; for 4h; | |
With lithium aluminium tetrahydride at 0 - 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With 1,10-Phenanthroline; sodium hydride at 100℃; for 18h; Glovebox; Sealed tube; | |
80% | With potassium <i>tert</i>-butylate; toluene-4-sulfonic acid hydrazide at 110℃; for 48h; Schlenk technique; Inert atmosphere; Sealed tube; | |
77% | With 1,10-Phenanthroline; potassium <i>tert</i>-butylate at 18℃; for 1h; Irradiation; Inert atmosphere; Glovebox; Schlenk technique; |
76% | With 2-Hydroxymethylpyridine; potassium <i>tert</i>-butylate at 20 - 80℃; for 24h; Schlenk technique; Inert atmosphere; | |
72% | With 1,10-Phenanthroline; potassium <i>tert</i>-butylate at 100℃; for 18h; Inert atmosphere; Sealed tube; | |
72% | With 8-quinolinol; potassium <i>tert</i>-butylate at 80℃; Schlenk technique; Green chemistry; | Arylation of Substituted Aryl Bromides; General Procedure General procedure: The substituted aryl bromide (1.0 mmol), 8-hydroxyquinoline (20 mol%) and KOtBu (2.0 mmol) were loaded into a Schlenk tube equipped with a Teflon-coated magnetic stir bar. The unactivated arene (8.0 mL or 80 equiv) was then added and the mixture was stirred at r.t. for 3-5 min. The Schlenk tube was placed in a preheated oil bath at 80 °C and the mixture was stirred for 18 h. After completion of the reaction as judged by GC analysis, the Schlenk tube was allowed to cool to r.t. and the contents quenched with H2O and diluted with EtOAc. The organic layer was separated, and the aqueous layer was extracted with EtOAc. The combined organic layer was dried over Na2SO4 and concentrated under reduced pressure. The crude residue was purified by flash column chromatography on silica gel to afford the desired biaryl product. |
61% | With 3-benzyl-1-(N-phenylcarbamoylmethyl)imidazolium chloride; potassium <i>tert</i>-butylate at 20 - 100℃; for 10h; Schlenk technique; Inert atmosphere; Green chemistry; | |
58% | With nickelocene; triethyl borane; potassium <i>tert</i>-butylate In tetrahydrofuran at 80℃; for 12h; Inert atmosphere; | |
53.6% | With N,N'-dibenzylpiperazine-2,5-dione; potassium <i>tert</i>-butylate at 130℃; for 18h; Sealed tube; Inert atmosphere; | |
52% | With molybdenum(II) acetate dimer; bathophenanthroline; potassium <i>tert</i>-butylate at 80℃; for 48h; Inert atmosphere; | |
51% | With iron(III) chloride; lithium hexamethyldisilazane; N,N`-dimethylethylenediamine at 20 - 80℃; Inert atmosphere; | |
40% | With potassium <i>tert</i>-butylate; <i>L</i>-proline; copper(I) bromide at 80℃; for 48h; Schlenk technique; Inert atmosphere; | |
30% | With potassium <i>tert</i>-butylate; N,N`-dimethylethylenediamine at 80℃; sealed tube; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | Stage #1: 4-Methylbiphenyl With hydrogen bromide; dihydrogen peroxide In tetrachloromethane; water at 20℃; for 1h; Irradiation; Stage #2: With ammonia; iodine In tetrachloromethane; water; acetonitrile at 20 - 60℃; for 4h; | |
90% | With ammonia; oxygen at 430℃; | 2.2.6 80g of oxalic acid was dissolved in 150g of water, followed by adding 85% phosphoric acid 35g, vanadium pentoxide 10g, chromium oxide 2g, nickel chloride 3g, lithium carbonate 0.8g, ammonium molybdate 1g, stirring until homogeneous, the addition of silica gel 120g after stirring for 24 hours after heated aging dewatered to 60-70% solids, the feeding into the fluidized bed or boiling bed 100 slowly warmed to about 12 hours, continue to heat up to 500 activated eight hours, and then cooled to 300 ° C2) Preparation of 4-cyanobiphenylThe molar 4-methyl-biphenyl: ammonia: oxygen = 1: 3:20, load of 0.05 (based on the weight of the catalyst weight per hour), the reaction pressure was 0.035MPa, different reaction temperatures were as follows: |
88% | With 1,10-Phenanthroline; dihydrogen peroxide; oxygen; ammonium formate In N,N-dimethyl acetamide at 80℃; for 6h; Autoclave; | 8 Example 8: Preparation of 4-cyanobiphenyl Preparation of 4-cyanobiphenyl: In a 500 ml autoclave, 34 g of 4-methylbiphenyl was added to the system.6.8 g of nano-ferrovanadium, 2 mL (0.1 equivalent) of hydrogen peroxide, 1.8 g (0.05 equivalent) of 1,10-phenanthroline,Ammonium formate 25.2 g (2 equivalents), N,N-dimethylacetamide 100 ml,The system was replaced with an oxygen atmosphere at a pressure of 5 atm and reacted at 80 ° C for 6 h.After the reaction was completed, the reaction system was mixed with 200 mL of water, and then extracted with 200 mL of ethyl acetate.The aqueous layer was extracted twice with ethyl acetate (200 mL*2), and the organic phase was combined and washed with brine.Dry over anhydrous sodium sulfate, and distill off the solvent under reduced pressure.Thus, the aromatic nitrile compound product, 41 g of 4-cyanobiphenyl, was obtained in a yield of 88%. |
87% | With tert.-butylnitrite; N-hydroxyphthalimide; palladium diacetate In acetonitrile at 70℃; for 24h; Inert atmosphere; Sealed tube; | |
81% | With tert.-butylhydroperoxide; ammonium fluoride; iodine; oxygen In water; dimethyl sulfoxide at 70℃; for 48h; Schlenk technique; Sealed tube; | |
60% | With hydroxylamine hydrochloride; 2,4,6-triphenylpyrylium tetrafluoroborate; oxygen; ammonium bromide In acetonitrile at 40℃; for 24h; Molecular sieve; Irradiation; | |
53% | Stage #1: 4-Methylbiphenyl With sodium azide; (4s,6s)-2,4,5,6-tetra(9H-carbazol-9-yl)isophthalonitrile; zinc trifluoromethanesulfonate In acetonitrile at 25℃; Irradiation; Stage #2: With trifluorormethanesulfonic acid In acetonitrile for 1h; | |
45% | With sodium azide; copper(ll) sulfate pentahydrate; [bis(acetoxy)iodo]benzene In acetonitrile at -40 - 25℃; Inert atmosphere; | |
Multi-step reaction with 2 steps 1: 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; dibenzoyl peroxide / tetrachloromethane / 2 h / 20 - 80 °C 2: ammonium hydroxide; iodine / 16 h / 20 - 60 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 18h;Sealed tube; | General procedure: To a stirred solution of Pd cNPs/C Fe3O4 (20 mg, 0.73 mol %) and DMF (3 mL) in a Schlenk tube with a teflon stopcock, iodobenzene (0.5 mmol), tri-n-butylphenylstanane (0.6 mmol) and K2CO3 (1.5 mmol) are added, sealed and heated at 100 oC for 10 h. After completion of the reaction, the catalyst is separated by an external magnet. After removal of catalyst, water was added to the solution and extracted with ethylacetate. The organic phase is dried over anhydrous Na2SO4. After evaporation of the solvents, the residue is subjected to column chromatography over silica gel (60-120 mesh), eluting with pet ether to afford the desired product. The biphenyl products were confirmed by 1H and 13C-NMR. The spectral data and spectra are shown in supporting information (Figure S5-S18). This procedure was followed for all the reactions listed in Table 2. |
94% | With [Pd{C6H2-(CH2CH2NH2)-(OMe)2-3,4}Br(PPh3)]; potassium carbonate; In N,N-dimethyl-formamide; at 90℃; for 0.05h;Microwave irradiation; | General procedure: A mixture of aryl halide (1 mmol), <strong>[960-16-7]phenyltributyltin</strong> (1.2 mmol), K2CO3 (1 mmol), and ortho-palladated catalyst (0.3 mol %) in DMF (2 mL) in a round-bottom flask equipped with a condenser was placed into a Milestone microwave reactor. Initially using a microwave power of 500 W, the temperature was ramped from room temperature to 90 C, (ca. 1 min), and then held at this temperature until the reaction was complete. During this time, the power was modulated automatically to keep the reaction mixture at 90 C. The mixture was stirred continuously using an appropriate magnet during the reaction. After the reaction was complete, the mixture was cooled to room temperature and diluted with H2O (30 ml) and Et2O (30 ml). The organic phase was washed with saturated KF solution (30 ml), and dried over MgSO4. The solution was filtered and the solvent evaporated using a rotary evaporator. The residue was purified by silica gel column chromatography [n-hexane or n-hexane/EtOAc (9:1)]. |
93% | With 4,4’‐bis(trimethylammoniummethyl)‐2,2’‐bipyridine; diamminedichloropalladium(II); sodium hydrogencarbonate; In water; at 110℃; for 6h;Sealed tube; | General procedure: A sealable tube, equipped with a magnetic stirring bar, was charged with aryl halide (1 mmol), organotin (1.2 mmol), NaHCO3 (2 mmol), and H2O (2 mL). In the case of tetramethyltin, the addition of tetraethylammonium iodide (TEAI, 1 mmol) was required. After the addition of PdCl2(NH3)2/L aqueous solution (1 mL H2O; different concentrations were required for various substrate/catalystratios), the tube was sealed under air using a Teflon-coated screw cap. The reaction vessel was then placed in an oil bath at 110 C for the indicated reaction duration (see Tables 2-4). After cooling of the reaction mixture to room temperature, the aqueous solution was extracted with hexane or ethyl acetate; the organic phase was dried over MgSO4, and the solvent was then removed under vacuum. Column chromatography on silica gel afforded the desired product (see Supplementary Materials for the copies of NMR spectra). |
91% | With tetrakis(triphenylphosphine) palladium(0); sodium acetate; at 80℃; for 3h;Inert atmosphere; Green chemistry;Catalytic behavior; | General procedure: A mixture of aryl bromide 1 (0.5 mmol), organotin reagent 2(0.6 mmol), NaOAc (0.5 mmol) and Pd(PPh3)4 (0.005 mmol) inPEG-400 (2 mL) was stirred at 80 C under an argon atmosphere for3-5 h until complete consumption of the aryl bromide was observed as judged by TLC. After being cooled to room temperature, the mixture was extracted three times with light petroleum ether (30-60C) (3 × 10 mL). The combined organic phases were concentrated under reduced pressure and the residue was purified by flash column chromatography on silica gel [light petroleum ether (30-60 C)/ethylacetate] to afford the desired product 3. |
88% | With bis-triphenylphosphine-palladium(II) chloride; In N,N-dimethyl-formamide; at 20℃; for 4h;Sealed tube; UV-irradiation; | General procedure: Aryl halide (1, 0.10 mmol) and a solution of PdCl2(PPh3)2 (0.01 mmol, 10 mol%) in DMF (2.34mL) were added to 13.5 mL glass vial containing a magnetic stirring bar. Aryl stannane (2, 0.30 mmol)and DMF (2.66 mL) were added to the mixture, and then the vial was sealed with PE (polyethylene)cap under air. The mixture was stirred under UV-light irradiation with 2×1.2 W UV-light (2 cm away,with cooling fan to keep the reaction room temperature) under air for 4 h. QuadraSilTM (100 mg) wasadded, and the resulting mixture was stirred for 2 min for quenching the reaction. After filtration(using a membrane filter) and evaporated, the residue was purified by preparative GPC withchloroform as eluent to afford the coupling product 3. |
35 mg | With tetrakis(triphenylphosphine) palladium(0); In toluene; at 110℃; for 8h;Inert atmosphere; | General procedure: In nitrogen atmosphere, sodium benzenesulfinate (1a, 0.3 mmol, 1.5 equiv, 49 mg), Ag2CO3 (0.3 mmol, 1.5 equiv, 83 mg) and Pd(PtBu3)2 (0.006 mmol, 3 mol %, 3 mg) were weighed in a 10 mL reaction tube. N,N-Dimethylacetamide (2 mL), hexabutyldistannane (2a, 0.2 mmol, 1 equiv, 116 mg, 101 μL) were then added in succession. The resulting reaction solution was stirred for 1 h at 140 C. The reaction system was filtered by siliga gel to remove the insoluble precipitate. The solution was then concentrated by rotovap under reduced pressure. Then in nitrogen atmosphere, Pd(PPh3)4 (0.01 mmol, 5 mol %, 12 mg), toluene (2 mL), and PhBr (0.2 mmol, 31 mg) were added, and the solution was stirred for 8 h at 110 C. The reaction was then concentrated by rotovap under reduced pressure to leave a crude residue, which was purified by silica gel column chromatography (petroleum ether) to give 1,1'-biphenyl (4b) in 81% isolated yield (25 mg) as white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With N,N,N,N,-tetramethylethylenediamine; copper diacetate; ammonium bicarbonate at 150℃; for 22h; sealed tube; | |
64% | Stage #1: 4-bromo-1,1'-biphenyl With n-butyllithium In tetrahydrofuran; hexane at -70 - 0℃; Stage #2: N,N-dimethyl-formamide In tetrahydrofuran; hexane at 0℃; for 1h; Stage #3: With ammonia; iodine In tetrahydrofuran; hexane; water at 0 - 20℃; | |
64% | Stage #1: 4-bromo-1,1'-biphenyl With n-butyllithium In tetrahydrofuran; hexane at -70 - 0℃; for 0.583333h; Stage #2: N,N-dimethyl-formamide In tetrahydrofuran; hexane at 0℃; for 1h; Stage #3: With ammonia; iodine In tetrahydrofuran; hexane; water at 0 - 20℃; for 2h; | 4.2. Typical experimental procedure for the conversion of aromatic bromides into aromatic nitriles with I2 General procedure: n-Butyllithium (1.67 M solution in hexane, 3.3 mL, 5.5 mmol) was added dropwise to a solution of p-bromotoluene (855 mg, 5.0 mmol) in THF (5 mL) at -70 °C. After 30 min, the resulting mixture was warmed and stirred for 5 min at 0 °C. Then, DMF (0.43 mL, 5.5 mmol) was added and the obtained mixture was stirred at 0 °C. After 1 h at the same temperature, aq NH3 (10 mL, 150 mmol) and I2 (1.40 g, 5.5 mmol) were added and the obtained mixture was stirred for 2 h at rt. The reaction mixture was quenched with satd aq Na2SO3 (15 mL) and extracted with Et2O (3×20 mL). The organic layer was washed with brine and dried over Na2SO4 to provide 4-methylbenzonitrile in over 80% purity. The product was purified by a short column chromatography on silica gel (Hexane/EtOAc=9:1) to give pure 4-methylbenzonitrile in 80% yield as a colorless solid. |
64% | Stage #1: 4-bromo-1,1'-biphenyl; N,N-dimethyl-formamide With magnesium In tetrahydrofuran at 20℃; Stage #2: With ammonia; iodine In tetrahydrofuran; water at 20℃; | Typical experimental procedure for the transformation of aromatic bromides into aromatic nitriles General procedure: To a flask containing Mg turnings (0.28 g, 14 mmol) was added p-bromotoluene (1.38 g, 8.0 mmol) in THF (8 mL) at room temperature. After being stirred for 2 h, DMF (1.3 mL, 12 mmol) was added to the reaction mixture. The obtained mixture was stirred for 2 h at room temperature. Then, aq NH3 (7 mL, 28-30%) and I2 (4.06 g, 1.6 mmol) were added to the reaction mixture. After being stirred overnight, the reaction mixture was poured into aq sat. Na2SO3 solution and extracted with CHCl3 (3 × 30 mL). The organic layer was dried over Na2SO4 and filtered. After removal of the solvent, the residue was purified by short column chromatography on silica gel (eluent: hexane / ethyl acetate = 9:1, v/v) to provide pure p-tolunitrile (0.77 g) in 67% yield. Most aromatic nitriles mentioned in this work are commercially available and were identified by comparison with the authentic samples. |
47% | With tert.-butylhydroperoxide; copper(II) nitrate trihydrate; water; acetic acid at 140℃; for 48h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 1 The first step 200 g tert-amyl alcohol that had been dried over molecular sieve and 140 g sodium tert-amyl alkoxide were introduced under a nitrogen atmosphere into a stainless steel reactor fitted with a reflux condenser and heating to 100C was performed with stirring to produce an alcoholate solution. Separately, 88 g <strong>[924-88-9]diisopropyl succinate</strong>, 97.0 g 4-chlorobenzonitrile, and 3.9 g 4-cyanobiphenyl were introduced into a 500 mL glass flask and were dissolved by heating to 90C with stirring to produce a solution of their mixture. This hot solution of the mixture was gradually added dropwise at a constant rate over 2 hours with vigorous stirring into the above-described alcoholate solution heated to 100C. After the completion of dropwise addition, heating and stirring were continued for 2 hours at 90C to obtain the alkali metal salt of a diketopyrrolopyrrole pigment composition. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With N,N,N,N,-tetramethylethylenediamine at 20℃; for 4h; UV-irradiation; | |
91% | With 1,10-Phenanthroline; potassium-t-butoxide at 18℃; for 1h; Irradiation; Inert atmosphere; Glovebox; Schlenk technique; | |
90% | With potassium peroxodisulfate; N-ethyl-N,N-diisopropylamine In lithium hydroxide monohydrate; dimethyl sulfoxide at 70℃; for 2h; chemoselective reaction; |
87% | With potassium-t-butoxide; toluene-4-sulfonic acid hydrazide at 110℃; for 24h; Schlenk technique; Inert atmosphere; Sealed tube; | |
81% | With potassium-t-butoxide at 100℃; for 16h; Schlenk technique; Sealed tube; Irradiation; | 2.2 General experimental procedures and characterizations General procedure: Method A: in a glove box, a 25 mL Schlenk tube equipped with a stir bar was charged with aryl iodides (0.25 mmol),KOtBu (56 mg, 0.5 mmol), and benzene (2.0 mL) was added by syringe. Then the Schlenk tube was sealed by a Teflon screw cap and placed in an oil bath at 100 °C (preheated to 100 °C) with one 24 W CFL (approximately 5 cm away). The reaction mixture was allowed to stir for 16 h. After being cooled down, the solvent was removed in vacuo and the residue was purified by chromatography on silica gel (eluent:diethyl ether/petroleum ether) to provide the corresponding product. Method B: in a glove box, a 25 mL Schlenk tube equipped with a stir bar was charged with aryl iodides (0.25 mmol), bathophenanthroline (8.3 mg, 0.025 mmol), KOtBu(56 mg, 0.5 mmol), and benzene (2.0 mL) was added by syringe. Then the Schlenk tube was sealed by a Teflon screw cap and placed with one 24 W CFL (approximately 3 cm away). The reaction mixture was allowed to stir for36 h. Then the solvent was removed in vacuo and the residue was purified by chromatography on silica gel (eluent:diethyl ether/petroleum ether) to provide the corresponding product. |
81% | With di-tert-butyl hyponitrite; sodium tertiary butoxide In dimethyl sulfoxide at 60℃; for 4h; Schlenk technique; Inert atmosphere; | Coupling Reaction of Arenes with Aryl Iodides (Tables 1-2): Representative Procedure(Table 1, Entry 2) General procedure: To a mixture of 4-iodoanisole (1a: 46.8 mg, 0.200 mmol), potassiumtert-butoxide (44.9 mg, 0.400 mmol) and di-tert-butyl hyponitrite (7.0 mg, 0.040 mmol) in a 20mL Schlenk tube was added benzene (2a: 2.1 mL, 24 mmol) and dimethyl sulfoxide (0.14 mL,2.0 mmol), and the resulting mixture was stirred at 60 C for 8 h. The reaction mixture wasquenched with a saturated NH4Cl aqueous solution (2.0 mL) and extracted with ethyl acetate (10mL x 3). Nonane was added as an internal standard for GC analysis, and an aliquot of theorganic layer was subjected to GC analysis. The combined organic layer was dried over MgSO4,filtered, and concentrated in vacuo. The residue was subjected to silica gel chromatography(hexane, PTLC) to give 4-methoxybiphenyl (3aa: 29.8 mg, 81% yield). |
80% | With 6-oxo-1,6-dihydropyridine-2-carboxylic acid dimethylamide; potassium-t-butoxide at 25℃; for 24h; Inert atmosphere; UV-irradiation; Green chemistry; | |
75% | With potassium-t-butoxide In dimethyl sulfoxide at 20℃; for 2h; Schlenk technique; Inert atmosphere; Irradiation; | |
74% | With (2-(methylamino)phenyl)methanol; potassium-t-butoxide at 100℃; for 24h; Sealed tube; | |
71% | With bathophenanthroline; sodium tertiary butoxide at 155℃; for 6h; Inert atmosphere; | |
71% | With potassium-t-butoxide; methyl[2-(methylamino)ethyl]amine at 80℃; sealed tube; Inert atmosphere; | |
70% | With silver(I) fluoride at 20℃; for 12h; Irradiation; Inert atmosphere; | |
69% | With 1,10-Phenanthroline; sodium hydride at 100℃; for 18h; Glovebox; Sealed tube; | |
68.1% | With 1,4-diphenylpiperazine-2,5-dione; potassium-t-butoxide at 130℃; for 18h; Sealed tube; Inert atmosphere; | |
56% | With di-tert-butyl peroxide; potassium-t-butoxide at 85℃; for 24h; Sealed tube; | |
50% | With iron(III) triphenantroline chloride; potassium-t-butoxide at 100℃; for 24h; Inert atmosphere; | |
46% | With N<SUP>1</SUP>,N<SUP>2</SUP>-bis(4,4,5,5,6,6,7,7,8,8,9,9,9-tridecafluorononyl)ethane-1,2-diamine; potassium-t-butoxide at 120℃; for 24h; Sealed tube; | General procedure for direct arylation of benzene with aryl halides General procedure: A reaction tube was charged with KOt-Bu (280.0 mg, 2.5 mmol) at room temperature, and then, 4-iodotoluene (109.0 mg, 0.5 mmol), fluorous ethylenediamine L (1170.0 mg, 1.5 mmol) and benzene (6.0 mL) were added. The resulting mixture was stirred at 120 °C for 24 h in this sealed tube equipped with a Teflon plug. After cooling to room temperature, (the fluorous ligand can be recovered by extraction with perfluorotoluene 5 mL × 3, 91% recovery yield ) the reaction mixture was quenched and extracted with ethyl acetate (10 mL × 3). The organic layers were combined, dried over Na2SO4 and concentrated under reduced pressure, and then purified by silica gel chromatography (petroleum ether) to yield the desired product as a white solid (52.9 mg, 63% yield). |
45% | With C14H9N4O(1-); potassium-t-butoxide at 120℃; for 24h; Inert atmosphere; | |
45% | With potassium-t-butoxide; butan-1-ol at 80℃; Inert atmosphere; Schlenk technique; | |
42% | With N,N'-diethylurea; potassium-t-butoxide at 130℃; for 24h; | 10 Example 10: (1) Put 10mol% of diethylurea (0.02mmol), 0.6mmol of potassium tert-butoxide, 0.2mmol of p-iodobenzonitrile and 2ml of benzene in the reaction tube,The reaction was heated and stirred, the temperature of the heating and stirring was 130°C, and the reaction time was 24h.(2) After the reaction, it is separated by column chromatography (the column packing is 300-400 mesh column chromatography silica gel, eluentIs: petroleum ether), the product 4-biphenyl nitrile can be obtained, and the yield is 42%. |
36% | With 1,10-Phenanthroline; potassium-t-butoxide at 100℃; for 24h; Inert atmosphere; Sealed tube; | |
32% | With potassium-t-butoxide; C38H58N2O8 at 120℃; for 24h; Sealed tube; Inert atmosphere; | |
With 1-(2-hydroxyethyl)piperazine; potassium-t-butoxide at 100℃; for 24h; Sealed tube; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With potassium phosphate; 1,3-bis[(diphenylphosphino)propane]dichloronickel(II); 4-methyl-N-phenyl-N-tosylbenzenesulfonamide In 1,4-dioxane at 110℃; Inert atmosphere; Schlenk technique; | |
95% | Stage #1: 4-cyanophenol With fluorosulfonyl fluoride; triethylamine In ethanol; water at 20℃; for 4h; Stage #2: phenylboronic acid With palladium diacetate; triethylamine In ethanol; water at 20℃; for 6h; | 4 Example 4: Preparation of 4-cyanobiphenyl In the air, 1mmol of 4-cyanophenol, 3mmol of triethylamine,4mL of 50% ethanol aqueous solution was added to a 10mL flask, and sulfonyl fluoride gas was slowly introduced,The reaction was stirred magnetically at room temperature. After 4 hours of reaction, 1mmol of phenylboronic acid,3mmol of triethylamine, 0.1mmol of palladium acetate, continue to react at room temperature for 6 hours,After the reaction is over, add 20mL saturated saline to quench the reaction,The reaction mixture was extracted with 40 mL of ethyl acetate to extract the reaction product, and the organic phases were combined,The filtrate is concentrated and separated by column chromatography to obtain the final product.The product structure was identified by proton nuclear magnetic resonance spectroscopy and mass spectrometry, and the separation yield was 95%. |
79% | Stage #1: 4-cyanophenol With potassium phosphate; triethylamine; bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate In 1,4-dioxane at 100℃; for 3h; Inert atmosphere; Stage #2: phenylboronic acid With 1,3-bis[(diphenylphosphino)propane]dichloronickel(II) In 1,4-dioxane at 100 - 110℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With copper(l) iodide; sodium azide In N,N-dimethyl-formamide at 120℃; for 5h; | 4.6. Procedure for transformation of 4-cyanobiphenyl 2a into 5-(biphenyl-4'-yl)-1H-tetrazole 5a To a solution of 4-cyanobiphenyl 2a (1.0 mmol,179.2 mg) in DMF (10.0 mL) were added CuI (0.25 mmol, 47.6 mg) and NaN3 (1.5 mmol, 97.5 mg). The obtained mixture was stirred for 5 h at 120 °C. The mixture was cooled to room temperature and then, sat.aq. NaHCO3 (15.0 mL) and water (5.0 mL) were added. The aqueous layer was washed with AcOEt (5.0 mL x 3), and then acidified with aq. 1.0 HCl (1 M) to become pH 2. The aqueous layer was extracted with AcOEt (5.0 mL x 3). The organic layer was dried over Na2SO4. After filtration and removal of the solvent, the residue was purified by neutral silica-gel column chromatography (eluent: AcOEt) to give 5-(biphenyl-4'-yl)-1H-tetrazole 5a (182.2 mg, 82%). 4.6.1. 5-(Biphenyl-4'-yl)-1H-tetrazole (5a) Yield: 182.2 mg (82%); white solid; Mp 248-249 °C, (lit [12]. Mp 247-249 °C): IR (neat) 2727, 1614, 1426, 1159, 1055, 991, 849, 744, 695 cm-1; 1H NMR (400 MHz, DMSO-d6): δ = 7.41 (t, 1H, J = 7.3 Hz), 7.50 (dd, 2H, J = 7.5, 7.3 Hz), 7.75 (d, 2H, J = 7.5 Hz), 7.91 (d, 2H, J = 7.8 Hz), 8.13 (d, 2H, J = 7.8 Hz); 13C{1H}NMR (100 MHz, DMSO-d6): δ = 123.2, 126.8, 127.6 (2C), 128.2 (2C), 129.1, 138.9, 142.7; HRMS (ESI) Calcd for C13H11N4 [M+H]+ = 223.0978, Found = 223.0974. |
75% | With sodium azide at 120℃; for 12h; | |
70% | With sodium azide; copper(II) ferrite In N,N-dimethyl-formamide at 130℃; for 20h; | Typical procedure for the synthesis of 5-Substituted 1H-Tetrazoles: General procedure: A mixture of nitrile (1 mmol), sodium azide (1.5 mmol), catalyst (40 mol%) and DMF (3 mL) was taken in a round-bottomed flask and stirred at 120 °C temperature for 12 h. After completion of the reaction the catalyst was separated from the reaction mixture with an external magnet and reaction mixture was treated with ethyl acetate (30 mL) and 5 N HCl (20 mL). The resultant organic layer was separated and the aqueous layer was again extracted with ethyl acetate (20 mL). The combined organic layers were washed with water, concentrated, and the crude material was chromatographed on silica gel (Hexane-EtoAc, 1:1) to afford the pure product. refText |
70% | With sodium azide at 120℃; for 20h; Green chemistry; | |
70% | With sodium azide; triethylamine hydrochloride | 16 General procedure: A mixture of a benzonitrile, 3a (310mg, 3mmol), 28 sodium azide (586mg, 9 mmol), and 29 triethylamine hydrochloride (1.24 g, 9 mmol) in 30 toluene (80 mL) was heated to 100°C for 24h with stirring. After cooling, the reaction mixture was extracted with water. Then, 36% 31 HCl was added dropwise to the aqueous layer. Precipitation occurred, which was filtered off and washed with water to provide 32 4a as white solid (395mg, 90%). Mp: 214-216°C. 1H NMR (500MHz, DMSO-d6): δ 8.04-7.02 (m, 2H), 7.62-7.57 (m, 3H) |
69% | With sodium azide at 120℃; for 24h; | |
With sodium azide; copper(II) oxide In N,N-dimethyl-formamide | Synthesis of 5-substituted-1H-tetrazoles (general procedure) General procedure: Synthesis of 5-substituted-1H-tetrazoles (general procedure): To a solution of aryliodide (1 mmol) in DMF (5 ml) was added sodium cyanide (1.2 mmol), catalyst(10 mol %) and the reaction mixture was stirred under heating at 100° C for appropriate time to obtain nitrile compound (see Table 1). To the nitrile compound generated in situ was added sodium azide (1.5 mmol) and the reaction was continued till the complete conversion of nitrile to tetrazole. After the completion of the reaction, the catalyst from the reaction mixture was easily separated out by centrifuging the reaction mixture. After the separation of the catalyst the crude material was then taken into ethyl acetate and washed with 5 N HCl and the layers separated. The organic layer was then washed with water, dried over anhyd sodium sulfate and concentrated to obtain the crude product. The crude product was purified by silica gel column chromatography using appropriate solvent mixtures to obtain the pure products (see Tables 1 and 2). Detailed experimental conditions and spectroscopic data were given insupplementary data. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | Stage #1: biphenyl-4-yl methanol With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; tert-butylhypochlorite In dichloromethane at 20℃; for 2h; Inert atmosphere; Stage #2: With ammonia; iodine In dichloromethane; water at 20℃; for 2h; Inert atmosphere; | |
99% | With ammonia; oxygen In tert-Amyl alcohol; water at 100℃; for 6h; Autoclave; High pressure; | |
94% | With ammonium hydroxide In <i>tert</i>-butyl alcohol at 120℃; for 24h; Sealed tube; Autoclave; | S7. Procedure for the synthesis of nitriles General procedure: The magnetic stirring bar and corresponding alcohol were transferred to 8 mL glass vial then 2 mL t-butanolsolvent was added. Then, 35 mg catalyst was added followed by the addition of aq. NH3. Then the vial wasf itted with septum, cap, and needle. The reaction vials were placed into a 300 mL autoclave (8 vials containingdif ferent substrates were placed at a time in the autoclave) and the autoclave was pressurized with 10 bar air.The autoclave was placed into an aluminium block and the temperature of the aluminum block was set in orderobtain 120 °C inside the autoclave. Temperature of the aluminum block was set to 130 oC to attain 120 oCinside the autoclave, which was considered as the reaction temperature. The reactions were allowed toprogress under continuous stirring for the required time at 120 °C. Af ter completion of the reaction, the autoclave was cooled down to room temperature and the remaining air was gradually discharged. Then, thecatalyst was f iltered-off, and washed with ethyl acetate. The solvent f rom the f iltrate containing the reactionproducts was purif ied by column chromatography. Products were analyzed by GC, GC-MS, and NMRspectroscopy. In the case of yields determined the by GC, 100 μL n-hexadecane was added to the reactionvial containing the products and diluted with ethyl acetate. Then the reaction mixture containing catalyst andproducts was filtered through a plug of silica and the filtrate containing product was analyzed by GC. |
91% | With 1,4-diaza-bicyclo[2.2.2]octane; TEMPOL; ammonia; copper(l) chloride In water; acetonitrile at 20℃; for 24h; | General procedure for the synthesis nitriles in Table 2 General procedure: To a 25-mL Schlenk tube equipped with a magnetic stirrer, CuCl (0.05 mol, 5 mol%), DABCO (0.10 mol, 10 mol%), 4-HO-TEMPO (0.05 mmol, 5 mol%) were added. Substrates 1 (1 mmol) and NH3 (aq, 25-28%, 3 mmol, 3.0 equiv) in CH3CN (2 mL) were added subsequently. Then the reaction mixture was stirred at room temperature for 24 h in the presence of an air balloon. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over anhydrous MgSO4. Subsequently, the combined organic layer was concentrated under reduced pressure and the crude product was purified by column chromatography to afford the corresponding products. |
86% | Stage #1: biphenyl-4-yl methanol With sodium azide; 2,4,5,6‐tetra‐9H‐carbazol‐9‐yl‐1,3‐benzenedicarbonitrile; zinc trifluoromethanesulfonate In acetonitrile at 25℃; Irradiation; Stage #2: With trifluorormethanesulfonic acid In acetonitrile for 1h; | |
80% | With copper(II) choride dihydrate; ammonium formate; potassium carbonate In neat (no solvent) at 135℃; for 24h; Sealed tube; Schlenk technique; Green chemistry; | |
80% | With copper(I) oxide; 1,10-Phenanthroline; oxygen; potassium ferrocyanide In dimethyl sulfoxide at 140℃; for 40h; Autoclave; | |
79% | With copper(II) perchlorate hexahydrate; trimethylsilylazide; 2,3-dicyano-5,6-dichloro-p-benzoquinone In 1,2-dichloro-ethane at 60℃; for 2h; | |
76% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; ammonium acetate; oxygen; nitric acid; acetic acid at 50℃; for 12h; Sealed tube; | 2.1 Experimental procedure for the aerobic conversion of benzyl alcohols to aromatic nitriles General procedure: 0.5 mmol substrate, 1.5 mmol NH4OAc, 0.15 mmol TEMPO, 2 mL AcOH and 0.15 mmol HNO3 weresuccessively added to a dried 45 mL tube filled with 1atm oxygen. Then the reaction tube was sealed andplaced in a constant-temperature oil bath to perform the reaction for 12 h. Once the reaction time wasreached, the mixture was cooled to room temperature. Then the mixture was alkalized to pH 7-8 with sodiumhydroxide aqueous solution. GC analysis of organic phase provided the GC yields of the products.Subsequently, the crude product from another parallel experiment was purified by column chromatography,and identified by 1H-NMR, 1C-NMR or GC-MS |
Multi-step reaction with 3 steps 1: potassium carbonate; fluorosulfonyl fluoride; dimethyl sulfoxide / 12 h / 20 °C 2: hydroxylamine hydrochloride; potassium carbonate / 20 °C 3: potassium carbonate; fluorosulfonyl fluoride / 12 h / 20 °C | ||
76 %Chromat. | With diammonium hydrogen orthophosphate; potassium carbonate In toluene at 80℃; for 20h; Sealed tube; Irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With sodium hydroxide In water at 80℃; for 6h; | 2.8 General Procedure for Hiyama Cross-CouplingReaction General procedure: To a stirring mixture of aryl halide (1 mmol), triethoxyphenylsilane(1.2 mmol) and NaOH (2 mmol) in H2O(4 mL),γ-Fe2O3-Pd-NHC-n-butyl-SO3Na (0.08 or 0.16 mol% based on Pd) was added. The resulting mixture was stirred at 80 °Cfor an appropriate time indicated by TLC monitoring. Aftercooling the reaction to room temperature, the catalyst wasseparated by an external magnet and washed with EtOAc.The product was extracted from the aqueous phase usingEtOAc (3 × 5 mL). After drying the combined organic layersover anhydrous Na2SO4,the solvent was evaporated togive the crude product. Purification of the crude product bycolumn chromatography on silica gel eluted with n-hexane:EtOAc = 30:1 produced the pure products (1-6). |
89% | With C58H78Cl4N6Pd2; tetrabutyl ammonium fluoride In toluene at 120℃; for 5h; | |
85% | With triethylamine In N,N-dimethyl-formamide at 90℃; for 4h; |
80% | With sodium hydroxide In water at 90℃; for 3.5h; Green chemistry; | |
80% | With sodium hydroxide In ethanol at 25℃; for 4.5h; Irradiation; Sealed tube; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With trimethylsilylazide; silver carbonate In dimethyl sulfoxide at 100℃; for 12h; | |
65% | With N-chloro-succinimide; silver(I) nitrite In 1,4-dioxane at 20℃; for 8h; Sealed tube; | 12 Example 12: Synthesis of 4-phenylbenzonitrile from 4-phenylphenylacetylene 4-phenylphenylacetylene 89 mg (0.50 mmol), silver nitrite 154 mg (1 mmol), N-chlorosuccinimide 133.5 mg (1 mmol)Add 10 mL of pressure-resistant sealed container in turn, and then add 5 mL of 1,4-dioxane.The mixture was stirred at room temperature, and the reaction was checked by TLC. The reaction was completed in 8 hours.The reaction solution was diluted with 10 mL of dichloromethane, and filtered to give a clear liquid.Separation by column chromatography (extraction of petroleum ether / ethyl acetate in a volume ratio of 30:1)Collecting eluate containing the objective product, the solvent was evaporated to give 4-phenyl-benzonitrile as a white solid 58.2mg (65% yield). |
32% | With tert.-butylnitrite; benzyl-methyl-amine In dimethyl sulfoxide at 110℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With triphenyl phosphite; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In N,N-dimethyl-formamide at 150℃; for 26h; Inert atmosphere; | 4.2. Desulfinylative palladium-catalyzed cross-coupling of aryl sulfinates with aryl halides; General procedure General procedure: A mixture of aryl halides (0.5 mmol), aryl sulfinates (0.75 mmol), Pd(dppf)Cl2 (2.5 mol %), P(OPh)3 (5 mol %), K2CO3 (1.5 mmol) and 2 mL of DMF in a schlenk tube was heated to 150 °C under inert atmosphere (24 h for aryl iodides and 26 h for aryl bromides). The reaction mixture was cooled to room temperature, diluted with ethyl acetate and filtered through a plug of Celite. The filtrate was washed sequentially with H2O and brine. The organic layer was separated, dried (Na2SO4), and concentrated under vacuum. The crude product was purified by column chromatography (silica gel; petroleum ether). All the products were analyzed by GC-MS. 1H NMR, 13C NMR and IR of only representative products are given, as all the products are highly reported. |
60% | With caesium carbonate; palladium dichloride In N,N-dimethyl-formamide at 185℃; for 20h; Inert atmosphere; Sealed tube; | |
51% | With palladium diacetate; XPhos In toluene at 120℃; for 40h; Inert atmosphere; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With tert.-butylhydroperoxide; copper(l) iodide; In N,N-dimethyl acetamide; water; at 130℃; for 20h; | General procedure: Boronic acid 1 (0.5mmol), benzyl cyanide 2 (0.75mmol), CuI (95mg, 0.5mmol), tert-BuOOH (70% aq, 144muL, 1mmol), and DMAc (2mL) were placed in a 25mL round flask. The reaction mixture was stirred at 130C (oil bath) for 20h under air. After cooling to the room temperature, the resulting mixture was poured to 15mL water and extracted with dichloromethane (3×5mL). The organic phase was combined and dried over anhydrous Na2SO4. Dichloromethane was evaporated under reduced pressure and the residue was purified by flash column chromatography on a silica gel to give the product 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With tert.-butylhydroperoxide; copper(l) iodide In N,N-dimethyl acetamide; water at 130℃; for 20h; | 2. General procedure for the synthesis of 3 General procedure: Boronic acid 1 (0.5mmol), benzyl cyanide 2 (0.75mmol), CuI (95mg, 0.5mmol), tert-BuOOH (70% aq, 144μL, 1mmol), and DMAc (2mL) were placed in a 25mL round flask. The reaction mixture was stirred at 130°C (oil bath) for 20h under air. After cooling to the room temperature, the resulting mixture was poured to 15mL water and extracted with dichloromethane (3×5mL). The organic phase was combined and dried over anhydrous Na2SO4. Dichloromethane was evaporated under reduced pressure and the residue was purified by flash column chromatography on a silica gel to give the product 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | Stage #1: 4-cyano-1,1'-biphenyl With [2,6-η6:η1-bis(2,4,6-trimethylphenyl)phenylthiolato]triethylphosphineruthenium(II)tetrakis[3,5-bis(trifluoromethyl)phenyl]borate; diethylphenylsilane at 20℃; for 18h; Glovebox; Inert atmosphere; Stage #2: With hydrogenchloride In diethyl ether at 20℃; for 1h; Glovebox; Inert atmosphere; | 2.1.2 General Procedure for Nitrile-to-Amine Reduction Catalyzed by [3a]+[BArF4]- (GP2) General procedure: In a glove box, a flame-dried GLC vial equipped with a magnetic stir bar is charged with[3a]+[BArF4]- (1.0 mol%) and Me2PhSiH (2a) (2.1 or 5.0 equiv). The indicated nitrile is added eitherin the glove box (for solid starting materials) or by micro syringe outside the glove box, and theresulting reaction mixture is maintained at room temperature for the indicated time. The reaction isquenched by the addition of a mixture of cyclohexane and tert-butyl methyl ether (90:10) containing4% Et3N (0.5 mL), and the resulting solution is filtered through a pad of Celite coated by a smalllayer of silica gel with a solution of cyclohexane and tert-butyl methyl ether (90:10) containing 4%Et3N (3-4 mL) as eluent. Solvents are removed under reduced pressure, and the residue isdissolved in Et2O (1 mL) followed by addition of HCl (2M in Et2O, 1.0 mL, 2.0 mmol, 10 equiv). Theresulting suspension is stirred for 1 h and filtered, affording the amines as hydrochloride salts aswhite to yellow solids. |
76% | Stage #1: 4-cyano-1,1'-biphenyl With phenylsilane; N,N,N-tributylbutan-1-aminium fluoride In tetrahydrofuran; toluene at 20℃; for 2h; Inert atmosphere; Schlenk technique; Stage #2: With hydrogenchloride In tetrahydrofuran; methanol; toluene for 1.5h; Inert atmosphere; Schlenk technique; | |
Multi-step reaction with 2 steps 1: tris(pentafluorophenyl)borate / chloroform-d1 / 1 h / 25 °C / Inert atmosphere 2: hydrogenchloride; water monomer / diethyl ether / 1 h / 20 °C |
Multi-step reaction with 2 steps 1: hydrogen; ammonium hydroxide / isopropanol / 15 h / 120 °C / 22502.3 Torr / Autoclave 2: hydrogenchloride / methanol | ||
Stage #1: 4-cyano-1,1'-biphenyl With hydrogen; C20H40MoN2O2P2; sodium triethylborohydride In tetrahydrofuran; toluene at 100℃; for 24h; Autoclave; Stage #2: With hydrogenchloride In diethyl ether; water monomer | ||
Multi-step reaction with 2 steps 1: C22H33N / neat (no solvent) / 16 h / 60 °C / Inert atmosphere; Glovebox; Sealed tube 2: hydrogenchloride / diethyl ether / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With mesoporous silica SBA-15 supported Cu2O nanoparticles In N,N-dimethyl-formamide at 120℃; for 8h; Green chemistry; | |
89% | With potassium carbonate In N,N-dimethyl-formamide at 120℃; for 15h; Inert atmosphere; | General procedure for the cyanation of aryl bromides andiodides using PdCuFe2O4NPs General procedure: To a 10 mL glass tube aryl halide (1 mmol), K4FeCN6(0.6 mmol,220 mg), K2CO3(1.5 mmol, 207 mg), catalyst (10 mg), and 2 mL DMFwere added and mixture was stirred for appropriate reaction timeat 120C under argon atmosphere. The progress of the reactionwas monitored by GC analysis. After completion of the reaction,reaction mixture was washed with 5 mL water and crude productwas isolated using dichloromethane (5× 1 mL). Organic extractswere combined together, evaporated and purified by flash chro-matography using hexane/EtOAc to give the desired aryl cyanideproducts. |
89 %Chromat. | With potassium carbonate In N,N-dimethyl-formamide at 120℃; for 15h; Inert atmosphere; | 2.3. General procedure for the cyanation of aryl bromides andiodides using palladium nanoparticles supported on (3-aminopropyl)triethoxysilane-modified copper ferrite nanoparticles General procedure: To a 10 mL glass tube aryl halide (1 mmol), K4FeCN6(0.6 mmol,220 mg), K2CO3(1.5 mmol, 207 mg), catalyst (10 mg), and 2 mL DMFwere added and mixture was stirred for appropriate reaction timeat 120C under argon atmosphere. The progress of the reactionwas monitored by GC analysis. After completion of the reaction,reaction mixture was washed with 5 mL water and crude productwas isolated using dichloromethane (5× 1 mL). Organic extractswere combined together, evaporated and purified by flash chro-matography using hexane/EtOAc to give the desired aryl cyanideproducts. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.2% | With C68H64Cl2N6P2Ru2(4+)*2F6P(1-)*2Cl(1-); caesium carbonate In N,N-dimethyl-formamide at 100℃; for 24h; Inert atmosphere; Green chemistry; | |
91% | With 1-methyl-1H-imidazole; oxygen; copper(ll) bromide In dimethyl sulfoxide at 100℃; for 24h; | 1 Typical procedure for CuBr2/NMI catalyzed aerobic oxidation of primary amines General procedure: To a 100 mL eggplant type Schlenk flask were added CuBr2 (67.0 mg, 0.3 mmol), corresponding amine (3 mmol) and a solution of NMI (73.8 mg, 0.9 mmol) in DMSO (6 mL). The flask was evacuated and purged with oxygen for three times before the flask was attached to a balloon filled with oxygen. Then the flask was heated at 100 °C for 24 h. After the flask was cooled down and the reaction mixture turned into green color, water (15 mL) and dichloromethane (15 mL) was added into the mixture. The water layer was extracted with dichloromethane (5 mL x 3) and the organic layers were combined. After removing the solvent, residue was purified by column chromatography (PE/EA = 100:1) to give the product. |
90% | With pyridine; 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate In dichloromethane at 20℃; for 12h; Inert atmosphere; |
Multi-step reaction with 2 steps 1: N-chloro-succinimide / 0.17 h / 20 °C / Milling 2: triethylamine / 0.33 h / 20 °C / Milling |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With bis(benzonitrile)palladium(II) dichloride; camphor-10-sulfonic acid; tetrabutyl ammonium fluoride; In tetrahydrofuran; at 50℃; for 3h; | General procedure: A mixture of arylhydrazine (1 mmol), triethoxy(phenyl)silane (1.2 mmol), Pd(PhCN)2Cl2 (5 mol%) and CSA (camphorsulfonic acid, 1 mmol) was stirred in thesolvent of TBAF (1 M in THF, 1.0 ml) at 50oC for 3 hours under air. After cooling down to room temperature, the insoluble was firstremoved by filtration and then the solvent was removed undera reduced pressure. The cross-coupling products were purified by silica gelchromatography with a mixture of petroleum ether and ethyl acetate. Thecross-coupling products were confirmed by melting point and spectroscopic (1HNMR, 13C NMR and HRMS-EI) analysis, which wereall consistent with the literature results. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With ammonia; dihydrogen peroxide; potassium iodide In tetrahydrofuran; water at 0 - 20℃; for 2h; | 4.5. Procedure for transformation of 4-cyanobiphenyl 2a into 4-biphenylcarboxamide 4a To a solution of 4-cyanobiphenyl 2a (1.0 mmol, 179.2 mg) in THF (8.0 mL) were added aq. NH3 (28%, 10.0 mL) and KI (3.0 mmol, 498.0 mg) at 0 °C. Aq. H2O2 (30%, 10.0 mL) was added dropwise to the mixture. The obtained mixture was stirred for 2 h at room temperature. Sat. aq. Na2SO3 solution (20.0 mL) was added to the reaction mixture and the product was extracted with AcOEt (10.0 mL x 3). The organic layer was dried over Na2SO4 and filtered. The solvent was removed under reduced pressure to give 4-biphenylcarboxamide 4a (183.4 mg, 93%). 4.5.1. 4-Biphenylcarboxamide (4a) Yield: 183.4 mg (93%); white solid; Mp 223 °C: IR (neat) 3404, 3170, 1644, 1614, 1407 cm-1; 1H NMR (400 MHz, DMSO-d6): δ = 6.51-5.54 (m, 2H), 6.61 (dd, 2H, J = 6.8, 7.7 Hz), 6.84-6.89 (m, 4H), 7.10 (d, 2H, J = 6.8 Hz), 7.17 (s, 1H); 13C{1H}NMR (100 MHz, DMSO-d6): δ = 126.5, 126.9, 128.0, 128.2, 129.0, 133.1, 139.2, 142.8, 167.6; HRMS (ESI) Calcd for C13H12ON [M+H]+ = 198.0913, Found = 198.0915. |
83% | With 3,4,5-trihydroxybenzoic acid; potassium hydroxide In ethanol; water at 20℃; Green chemistry; | |
83% | With water extract of pomelo, peel at 150℃; for 2h; Sealed tube; Green chemistry; | 3.3. General Procedure for the Hydrolysis of Nitriles in WEPPA (Taking 1a as an Example General procedure: Benzonitrile 1a (103 mg, 1.0 mmol) and WEPPA (2.0 mL) were added into a 10-mL closed tubewith a stir bar. Then the reaction was stirred in a closed vessel synthesis reactor at 150 C for 0.5 h.After cooling to ambient temperature, the resulting precipitate was collected by filtration, washed withice water, and further dried in a vacuum drying oven. The filtrate was evaporated under reducedpressure. The resultant residue was purified by silica gel column chromatography (eluent: petroleumether (35-60 C)/EtOAc = 2:1 to 0:1, v/v). Finally, these two parts were combined to produce the desiredbenzamide 2a with a 94% yield. |
70% | With oxygen; ammonium chloride; copper(l) chloride In N,N-dimethyl-formamide; acetonitrile at 25℃; Sealed tube; | 13 Synthesis Example 13 Synthesis of p-phenylbenzamide In the reaction vessel was added 30mol% CuCl, the reaction tube was evacuated, filled with oxygen,In an oxygen atmosphere, 0.2 mmol of p-phenylbenzonitrile, 0.6 mmol of ammonium chloride, 1 ml of acetonitrile and 1 ml of N, N-dimethylformamide were added, the reaction vessel was sealed, and reacted at 25 ° C,After the reaction is completed, it is washed with water, extracted with ethyl acetate, dried and concentrated by evaporation under reduced pressure to remove the solvent. The crude product is separated by column chromatography to obtain the desired product in a yield of 70%. |
60% | With water In ethanol at 130℃; for 1h; Microwave irradiation; | |
22% | With Rhodococcus rhodochrous ATCC BAA 870 cobalt nitrile hydratase In aq. buffer at 30℃; Enzymatic reaction; | Composition of the reaction mixture General procedure: 1800 μL (90%) Tris buffer (50 mM, pH 7.6) and 200 μL(10%) of methanol or acetone. In a 2 mL Eppendorf, NHase (10 mg) was added followed by Trisbuffer. Nitrile substrate (10 mg dissolved in 200 μL methanol or acetone) was added to the 2 mLEppendorf tube. (If an amine group was present on the nitrile substrate a Tris buffer of pH 9 wasused). The reaction mixture was incubated at 30 °C on an ESCO Provocell microplateshaker/incubator (Esco Technologies, Halfway House, South Africa) (199 rpm). The reaction wasallowed to proceed for 24 h, 48 h or 5 d, depending on conversion, as monitored by TLC analysis.Ethyl acetate and water were added to the reaction mixture, and after separation, the organic layerwas concentrated under reduced pressure, and the resulting mixture was then purified by silica gelcolumn chromatography eluting with 20% to 90% ethyl acetate/ hexane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With tetrakis(triphenylphosphine) palladium(0); sodium azide; XPhos In acetone at 25℃; for 12h; Schlenk technique; | 6 Example 6: Synthesis of Biphenyl-4-carbonitrile (2f) Weigh 4- (chloromethyl) biphenyl (101.3 mg, 0.5 mmol)Sodium azide (65.0 mg, 1.0mmol),Tetraphenylphenylphosphine palladium (5.8 mg, 0.005 mmol,)And 2-dicyclohexylphosphine-2 ', 4', 6'-triisopropylbiphenyl (23.8 mg, 0.05 mmol) were added successively to a 25 mL Schlenk reaction flask,Acetone (3.0 mL) was added and allowed to react in an oil bath at 25 ° C for 12 h. After completion of the reaction, the solvent was removed under reduced pressure,Using petroleum ether / ethyl acetate as eluent, silica gel column separation, Biphenyl-4-carbonitrile yield95%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 53 %Spectr. 2: 20 %Spectr. | With 2-chloro-[1,10]phenanthroline; {Pd(2,2':6',2''-terpyridine)(acetonitrile)}(BF4)2; N-fluorobis(benzenesulfon)imide In acetonitrile at 25℃; for 20h; Overall yield = 144 mg; | 4 Example 4. 4'-Cyano-2-fluorobiphenyl (3da) and 4'-cyano-4-fluorobiphenyl (3db) A mixture of palladium complex SI (27.7 mg, 50.0 μιηο, 5.00 mol%) and 2-chloro- phenanthroline (10.7 mg, 50.0 μιηο, 5.00 mol%.) was dissolved in acetonitrile (5.0 mL). This mixture was added to a 20 mL vial containing a solution of NFBS (615 mg, 2.00 mmol, 2.00 equiv.) and 4-cyanobiphenyl (179 mg, 1.0 mmol, 1.0 equiv.) in acetonitrile (5.0 mL, final c = 0.10 M). The reaction mixture was stirred for 20 hours at 25 °C. The remaining oxidant was quenched by adding a solution of Na2S203 (H20)5 (1.22 g, 5.00 mmol, 5.00 equiv.) in water (20 mL) and stirring for 30 min. The mixture was added to a separately funnel with 50 mL dichloromethane. The aqueous layer was extracted with dichloromethane (3 x 50 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo at 40 °C to afford a pale yellow solid. The residue was dissolved in dichloromethane (2 mL), loaded onto a short plug of silica (20 g) and eluted with (0377) dichloromethane. and concentrated in vacuo to afford a pale yellow solid (191 mg) containing the title compounds (144 mg, 0.73 mmol, 73% yield, 3da: 3db (73 :27)), 4-cyano-biphenyl and minor inseparable impurities. The 4-cyano-biphenyl content of the residue was established by 1H NMR spectrum of the mixture (diagnostic signal at δ 7.48 ppm (m, 2H)). The yield and selectivity were determined by 19F using l,4-bis(trifluoromethyl)benzene as an internal standard (standard: δ -63.4 ppm, 6 F; compared with product peaks at δ-113.8 and - 118.2 ppm; first relaxation time of 10 s to ensure accurate integration). The spectra matched the reported spectra for the title compounds and authentic samples. See Zhou et al., J. Org. Chem., 2012, 77, 10468-10472; Bernhardt et al., Angew. Chem., Int. Ed, 2011, 50, 9205- 9209. |
With [(terpy)Pd(2-Cl-phen)][BF4]; N-fluorobis(benzenesulfon)imide In acetonitrile at 25℃; for 20h; Overall yield = 61 %; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With palladium on activated charcoal; deuterium In hexane; water-d2; ethyl acetate at 100℃; for 24h; | 17 Example 17In this Example, an aromatic deuterated methyl compound was prepared by the following preparation method,The reaction is as follows: 4-Cyanobiphenyl (1 g) and palladium on carbon (0.1 g) were mixed in n-hexane: ethyl acetate: Deuterium water (20 mL: 2 mL: 2 mL) at 2 MPa deuterium pressure,100 degrees stirring for 24 hours, after the reaction was filtered to give 4-demethyl methyl benzoate,Yield 70%, deuterium rate 98%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | With N,N'-diethylurea; at 120℃; for 24h;Schlenk technique; Sealed tube; Inert atmosphere; | General procedure: Aryl iodides (0.2 mmol) t-BuOK (0.6 mmol, 3.0 equiv), and U6 (0.02 mmol, 10 mol%) were added in dried Schlenk tubes. Benzene (2 mL) were added into tubes by syringe. The septum-sealed tube was evacuated and refilled with nitrogen three times. The mixture was stirred under a nitrogen atmosphere in sealed Schlenk tubes at 120 C for 24 h. The reaction was cooled down to room temperature. The mixture was filtered through a short plug of silica gel, washed with a copious amount of ethyl acetate. The combined organic phase was concentrated under vacuum. The product was purified through flash column chromatography on 300-400 mesh silica gel with hexane/ethyl acetate as eluent. Solvent was removed under vacuum to give the pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With 1,4-diaza-bicyclo[2.2.2]octane; copper(I) oxide; phenylsilane; ammonia In 1-methyl-pyrrolidin-2-one at 180℃; for 24h; Sealed tube; chemoselective reaction; | General procedure for the cyanation of aryl iodide with CO2 and NH3 General procedure: Under nitrogen atmosphere, Cu2O (10 mol %), DABCO (25 mol %), and a stirring bar were added into a 10 mL oven-dried sealed glass tube (as shown in Figure S1). Then NMP (0.5 mL), aryl iodides (0.125 mmol, 1.0 equiv.) and PhSiH3 (0.75 mmol, 6 equiv.) were injected by syringe. The tube was then sealed and CO2 (0.67 mmol, 5.4 equiv., 15 mL) as well as NH3 (0.67 mmol, 5.4 equiv., 15 mL) were injected by syringe after N2 was removed under vacuum. Finally, the mixture was stirred for 24 hr in a pre-heated-to-130 °C alloyed block. After the reaction was finished, the tube was cooled to room temperature and the pressure was carefully released. The yield of were measured by GC analysis using dodecane as the internal standard or by flash chromatography on silica gel (petroleumether/ethyl acetate). |
88 %Chromat. | With phenylsilane; ammonia; copper diacetate In N,N-dimethyl-formamide at 160℃; for 10h; Sealed tube; | 9 Example 9: Preparation of 4-Phenylbenzonitrile from 4-Phenyl Iodobenzene (9) Under a nitrogen atmosphere, copper acetate (20 mol%, 4.6 mg) and a magnet were added to a previously baked 10 mL glass pressure tube. Then, N,N-dimethylformamide (0.5 mL), 4-phenyl iodobenzene (0.125 mmol, 1.0 equiv., 35.0 mg) and phenylsilane (3.0 equiv., 40.6 mg) were added. The pressure tube was sealed, the tube air was removed and charged with carbon dioxide (5.0 equiv., 15 mL) and ammonia gas (5.0 equiv., 15 mL). After the addition, the glass pressure tube was placed in a metal module that had been preheated to 160[deg.] C. and stirred for 10 hours. After the reaction was completed, the reaction system was cooled to room temperature and pressure was slowly released. Using dodecane as an internal standard, the yield of the gas chromatograph was 88%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
5%Spectr.; 9%Spectr. | General procedure: To a suspension of the DA 12- sodium salt, butyl chloride or cyclohexyl bromide (1 equiv.) was added dropwise at -40 C and the reaction mixture was kept at the same conditions for 40÷60 min. Afterwards required alkyl bromide (1.1÷1.4 equiv.) was added (Table 1, entries 2÷5) and reaction mixture was treated as described above for dienone 2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
14%Spectr. | General procedure: To a suspension of the DA 12- sodium salt, butyl chloride or cyclohexyl bromide (1 equiv.) was added dropwise at -40 C and the reaction mixture was kept at the same conditions for 40÷60 min. Afterwards required alkyl bromide (1.1÷1.4 equiv.) was added (Table 1, entries 2÷5) and reaction mixture was treated as described above for dienone 2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
10%Spectr. | General procedure: To a suspension of the DA 12- sodium salt, butyl chloride or cyclohexyl bromide (1 equiv.) was added dropwise at -40 C and the reaction mixture was kept at the same conditions for 40÷60 min. Afterwards required alkyl bromide (1.1÷1.4 equiv.) was added (Table 1, entries 2÷5) and reaction mixture was treated as described above for dienone 2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6%Spectr.; 30%; 10% | General procedure: To a suspension of the DA 12- sodium salt, butyl chloride or cyclohexyl bromide (1 equiv.) was added dropwise at -40 C and the reaction mixture was kept at the same conditions for 40÷60 min. Afterwards required alkyl bromide (1.1÷1.4 equiv.) was added (Table 1, entries 2÷5) and reaction mixture was treated as described above for dienone 2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
10%Spectr.; 19%Spectr. | General procedure: To a suspension of the DA 12- salt, an alkylbromide (2-2.1 equiv.) was added dropwise with stirring at -40 C. Then the reaction mixture was treated as described above for dienone 2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
10%Spectr.; 55% | General procedure: The alkali metal (ca. 2.05÷2 equiv., see Tables 1 and 2) was added to a stirred suspension of carbonitrile 1 in liquid ammonia at -33 C under evaporating ammonia atmosphere. The obtained mixture was stirred for 5 min under the same conditions resulting in dark-brown suspension of the DA 12- salt. In order to generate monoanion 1-H4?- the DA 12- salt was quenched by equiv. amount of MeOH or NH4Cl (Table 2), giving dark-red solution of anion 1-H4?- salt. To a suspension of the of the DA 12- sodium salt, n-butyl chloride or cyclohexyl bromide (1-1.1 equiv.) was added dropwise with stirring at -40 C. The reaction mixture was stirred for 1 h under evaporating ammonia atmosphere at -33 C, then it was brought into contact with atmosphere, Et2O (20 mL) was added and stirring was continued until NH3 evaporated completely and r.t. reached. Afterwards H2O (30 mL) was added to the residue and products were extracted with Et2O (3 x 20 mL). The combined organic extracts were washed with H2O (3 x 20 mL) and dried (MgSO4). Here and below the composition of the reaction mixtures obtained after Et2O evaporation was determined based on 1H NMR spectroscopy and GCMS data. Individual products were separatedby TLC on plates with a fixed layer of silica gel (Silica gel 60 PF254 containing gypsum) and a hexane/Et2O mixture (from 9/1 to 8:1 v/vratio) as eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
10%Spectr.; 36% | General procedure: The alkali metal (ca. 2.05÷2 equiv., see Tables 1 and 2) was added to a stirred suspension of carbonitrile 1 in liquid ammonia at -33 C under evaporating ammonia atmosphere. The obtained mixture was stirred for 5 min under the same conditions resulting in dark-brown suspension of the DA 12- salt. In order to generate monoanion 1-H4?- the DA 12- salt was quenched by equiv. amount of MeOH or NH4Cl (Table 2), giving dark-red solution of anion 1-H4?- salt. To a solution of anion 1-H4?- sodium salt in liquid ammonia alkyl bromide (1÷1.5 equiv., Table 2) was added dropwise at -33 C, then the reaction mixture was treated as described above for dienone 2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With cesium fluoride; lithium hexamethyldisilazane; In Dimethyl ether; at 110℃; for 12h;Green chemistry; | General procedure: Lithium bis(trimethylsilyl)amide (66.8 mg, 0.4 mmol) and cesium fluoride (30.4 mg, 0.2 mmol) were placed in a microwave tube in a glove box. Add 0.4 mL of cyclopentyl methyl ether, Then <strong>[95-52-3]2-fluorotoluene</strong> (66 muL, 0.60 mmol) and benzonitrile (20 muL, 0.20 mmol) were added separately using a micro syringe. which was taken out from the glove box and refluxed at 110 C for 12 hours. After cooling to room temperature, the reaction was capped and three drops of water were added to quench the reaction. The solvent was removed under reduced pressure and the crude product was purified by column chromatography ( petroleum ether: ethyl acetate = 20:1) to give 2-phenylindole (34.7 mg) , 90% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 93% 2: 7% | With dibromido-(1,1'-diisopropyl-3,3'-ethylenedibenzimidazoline-2,2-diylidene)palladium(II); potassium carbonate; triphenylphosphine In toluene at 120℃; for 20h; Autoclave; | |
1: 23% 2: 77% | With dibromido-(1,1'-diisopropyl-3,3'-ethylenedibenzimidazoline-2,2-diylidene)palladium(II); potassium carbonate; triphenylphosphine In toluene at 120℃; for 20h; Autoclave; | |
With dibromido-(1,1'-diisopropyl-3,3'-ethylenedibenzimidazoline-2,2-diylidene)palladium(II); potassium carbonate; triphenylphosphine In toluene at 120℃; for 20h; | 2 Carbonylative Suzuki-Miyaura coupling reaction of aryl bromides with arylboronic acid by C1 General procedure: Carbonylative Suzuki-Miyaura coupling reactions of aryl bromides with aryl boronic acids catalyzed by the palladium catalyst C1 in the presence of two equivalent of triarylphosphine, where the selectivity in the carbonylation product of was controlled by the CO pressure were also performed as shown in Scheme 8 and Table 3. The following components and conditions were used: C1 (1.0 mol %), PPh3 (2.0 mol %), aryl bromide (1.0 mmol), aryl boronic acid (1.2 mmol), K2CO3 (2.0 mmol), toluene (5.0 mL), CO (200 psi), 120° C., 20 hrs. |
With dibromido-(1,1'-diisopropyl-3,3'-ethylenedibenzimidazoline-2,2-diylidene)palladium(II); potassium carbonate; triphenylphosphine In toluene at 120℃; for 20h; | 2 Carbonylative Suzuki-Miyaura coupling reaction of aryl bromides with arylboronic acid by C1 General procedure: Carbonylative Suzuki-Miyaura coupling reactions of aryl bromides with aryl boronic acids catalyzed by the palladium catalyst C1 in the presence of two equivalent of triarylphosphine, where the selectivity in the carbonylation product of was controlled by the CO pressure were also performed as shown in Scheme 8 and Table 3. The following components and conditions were used: C1 (1.0 mol %), PPh3 (2.0 mol %), aryl bromide (1.0 mmol), aryl boronic acid (1.2 mmol), K2CO3 (2.0 mmol), toluene (5.0 mL), CO (200 psi), 120° C., 20 hrs. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With 1,10-Phenanthroline; oxygen; copper(II) oxide; potassium ferrocyanide In dimethyl sulfoxide at 120℃; for 40h; Autoclave; | 2.2. General procedure for the conversion of arylacetic acids to aromatic nitriles General procedure: The reaction was carried out in a 40 mL stainless steel autoclave lined with Teflon. Typically, 0.5 mmol substrate, 0.6 mmol K4Fe(CN)6, 0.1mmol CuO, 0.5 mmol 1,10-phenanthroline and 2 mL DMSO were added into the reactor and 1.5MPa of oxygen was filled. Then the reaction system was heated under magnetic stirring at 120°C for 40h. Once the reaction time was reached, the mixture was cooled to room temperature. GC analysis of the reaction mixture provided the GC yields of the products. In addition, the crude product from another parallel experiment was purified by column chromatography, and identified by 1H NMR and 13C NMR. |
90 %Chromat. | With iron(III) trifluoromethanesulfonate; sodium nitrite In dimethyl sulfoxide at 50℃; for 10h; Inert atmosphere; Sealed tube; | Nitriles 2a-r: General Procedure General procedure: A tube of approximate volume 45 mL was charged with theappropriate arylacetic acid (0.5 mmol), NaNO2 (3 mmol),Fe(OTf)3 (1 mmol), and undried DMSO (2 mL), and the air in thetube was replaced by argon gas. The tube was sealed and themixture was heated with magnetic stirring at 50 °C for 10 h,then cooled to r.t. The solvent was evaporated, and the residuewas purified by column chromatography (silica gel).Biphenyl-4-carbonitrile (2a)11bWhite solid; yield: 77.1 mg (86%); m.p. 84-86°C. 1H NMR (400MHz, CDCl3): = 7.76 (d, J = 8.4 Hz, 2 H), 7.71 (d, J = 8.4 Hz, 2 H),7.61-7.63 (m, 2 H), 7.50-7.53 (m, 2 H), 7.44-7.48 (m, 1 H). 13CNMR (100 MHz, CDCl3): = 145.7, 139.2, 132.6, 129.1, 128.7,127.8, 127.3, 119.0, 110.9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 89.6% 2: 6.8% | With potassium carbonate; triethylamine In water; N,N-dimethyl-formamide for 6h; Irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With ammonium bicarbonate; copper(II) nitrate In dimethyl sulfoxide at 140℃; for 30h; Autoclave; | Representative Procedure for Conversion of Various Arylethenesto Aromatic Nitriles General procedure: To a stainless steel autoclave lined with Teflon, 0.5 mmol substrate,0.075 mmol Cu(NO3)2, 1 mmol (NH4)2CO3, and 2 mLDMSO were added. Then the reactor was filled with 2 MPaoxygen and was heated under magnetic stirring at 140 °C for 30h or 40 h (Caution: the use of the high-pressure oxygen ispotentially hazardous. Thus, experiments using the high-pressureoxygen must only be carried out under rigorous safety precautions,and it is required to use the appropriate high-pressurereactor to avoid the potential leakage or explosion of the gas).Once the reaction time was reached, the mixture was cooled toroom temperature, diluted with 30 mL diethyl ether, and filteredvia a Celite pad. The organic mixture was washed withwater (3 × 5 mL), dried with anhydrous sodium sulfate, and concentratedin vacuum. GC analysis provided the GC yields of theproduct with an internal standard. In addition, the combinedcrude product from another 1-5 parallel experiments was purifiedby column chromatography and identified by 1H NMR and13C NMR spectroscopy. All the products are the known compounds,and the analytical data of several typical compoundsare as follows: |
Tags: 2920-38-9 synthesis path| 2920-38-9 SDS| 2920-38-9 COA| 2920-38-9 purity| 2920-38-9 application| 2920-38-9 NMR| 2920-38-9 COA| 2920-38-9 structure
[ 64113-85-5 ]
4-Methyl-[1,1'-biphenyl]-2-carbonitrile
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[ 114772-53-1 ]
4'-Methyl-[1,1'-biphenyl]-2-carbonitrile
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[ 5447-87-0 ]
2-(1-Phenylethylidene)malononitrile
Similarity: 0.92
[ 64113-85-5 ]
4-Methyl-[1,1'-biphenyl]-2-carbonitrile
Similarity: 0.93
[ 114772-53-1 ]
4'-Methyl-[1,1'-biphenyl]-2-carbonitrile
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[ 5447-87-0 ]
2-(1-Phenylethylidene)malononitrile
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