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Transition-Metal-Free Borylation of Aryl Bromide Using a Simple Diboron Source
Lim, Taeho ; Ryoo, Jeong Yup ; Han, Min Su ;
Abstract: In this study, we developed a simple transition-metal-free borylation reaction of aryl bromides. Bis-boronic acid (BBA), was used, and the borylation reaction was performed using a simple procedure at a mild temperature. Under mild conditions, aryl bromides were converted to arylboronic acids directly without any deprotection steps and purified by conversion to trifluoroborate salts. The functional group tolerance was considerably high. The mechanism study suggested that this borylation reaction proceeds via a radical pathway.
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Purchased from AmBeed: 20469-65-2 ; 13675-18-8 ; 2564-83-2 ; 872-31-1 ; 192863-35-7 ; 871231-46-8 ; 192863-36-8 ; 6793-92-6 ; 3972-65-4 ; 2398-37-0 ; 850623-47-1 ; 929626-22-2 ; 705254-31-5 ; 580-13-2 ; 2635-13-4 ; 623-12-1 ; 1015082-71-9 ; 52415-29-9 ; 23145-07-5 ; 619-42-1 ; 99-90-1 ; 192863-37-9 ; 578-57-4 ; 407-14-7 ; 216434-82-1 ; 668984-08-5 ; 423118-47-2 ; 108-85-0 ; 252726-24-2 ; 101-55-3 ; 850623-36-8 ; 4923-87-9 ; 1394827-04-3 ; 850623-42-6 ; 438553-44-7 ; 460-00-4 ; 1187951-62-7 ; 705254-34-8 ; 111-83-1 ; 111-83-1 ; 906007-40-7 ; 1443282-44-7 ; 1000160-76-8 ; 1111733-01-7 ; 99-90-1
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CAS No. : | 20469-65-2 |
Formula : | C8H9BrO2 |
M.W : | 217.06 |
SMILES Code : | COC1=CC(OC)=CC(Br)=C1 |
Synonyms : |
3,5-Dimethoxybromobenzene
|
MDL No. : | MFCD06200685 |
InChI Key : | KRWRFIMBWRVMKE-UHFFFAOYSA-N |
Pubchem ID : | 639187 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
60% | With magnesium; | (4-Methoxy-3-nitro-phenyl)-(3,5-dimethoxy-phenyl)-methanol was prepared analogously to 3-(4-methoxy-3-nitro-phenyl)-(3,4-dimethoxy-phenyl)-methanol using 3,5-dimethoxy-bromobenzene (5.0 g, 23.0 mmol), magnesium turning (0.6 g, 23.0 mmol) and 4-methoxy-3-nitro-benzaldehyde (3.5 g, 19.2 mmol). The crude product was purified by flash chromatography (silica gel, Hexane:EtOAc 1:1) to afford (4-methoxy-3-nitro-phenyl)-(3,5-dimethoxy-phenyl)-methanol (3.7 g, 60%) as an oil: 1H NMR (CDCl3) δ 7.88 (s, 1H), 7.54-7.50 (dd, J=2, 8 Hz, 1H), 7.04 (d, J=8 Hz, 1H), 6.38 (d, J=1 Hz, 1H), 5.72 (d, J=3 Hz, 1H), 3.93 (s, 3H), 3.76 (s, 6H), 2.45 (d, 2 Hz, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | In tetrahydrofuran; water; | 4.6.2.34 3-(3,4-Bis-difluoromethoxy-phenyl)-3-(3,5-dimethoxy-phenyl)-acrylonitrile (E and Z Isomers) n-Butyl lithium (2.5 M, 3.7 mL) was added to s stirred solution of 3,5-dimethoxy-bromobenzene (2.0 g, 9.2 mmol) in THF (15 mL) at -65 C. After stirring for 30 min, a solution of <strong>[127842-54-0]3,4-bis-difluoromethoxy-benzaldehyde</strong> (2.0 g, 8.4 mmol) in THF (15 mL) was added slowly. The resulting mixture was stirred at -65 C. for 6 h and then quenched with isopropanol (5 mL). Water (40 mL) was added and the mixture was extracted with ether (3*60 mL). The combined organic layers were washed with water (2*40 mL), brine (40 mL), and dried (MgSO4). Solvent was removed and the residue was purified by flash chromatography (Silica gel, Hexane:EtOAc 7:3) to afford (3,4-bis-difluoromethoxy-phenyl)-(3,5-dimethoxy-phenyl)-methanol (1.3 g, 42%): 1H NMR (CDCl3) delta 7.32 (m, 1H), 7.19 (m, 2H), 6.86-6.19 (m 5H), 5.69 (d, J=2 Hz, 1H), 3.76 (s, 6H), 2.47 (d, J=2 Hz, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 90.0℃; for 4.0h;Inert atmosphere; | a) 3,5-Dimethoxy-1,1'-biphenyl I115 A suspension of <strong>[20469-65-2]1-bromo-3,5-dimethoxybenzene</strong> (5.0 g, 23.0 mmol), phenylboronic acid (2.8 g, 23.0 mmol), Pd(dppf)Cl2 (0.57 g, 0.69 mmol) and potassium carbonate (4.8 g, 34.6 mmol) in 1,4-dioxane (80 ml.) and water (20 ml.) was heated at 90 C under N2 for 4 h. The mixture was diluted with water, extracted with EtOAc and the combined organic extracts were dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (Pet.ether/EtOAc = 500/1 to 200/1 to 100/1) to give the title compound (5.2 g, 100 %) as a white solid. LCMS-C: Rt 2.47 min; m/z 215.0 [M+H]+. |
100% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 90.0℃; for 4.0h;Inert atmosphere; | A suspension of <strong>[20469-65-2]1-bromo-3,5-dimethoxybenzene</strong> (5.0 g, 23.0 mmol), phenylboronic acid (2.8 g, 23.0 mmol), Pd(dppf)Cl2 (0.57 g, 0.69 mmol) and potassium carbonate (4.8 g, 34.6 mmol) in 1,4-dioxane (80 ml.) and water (20 ml.) was heated at 90 C under N2 for 4 h. The mixture was diluted with water, extracted with EtOAc and the combined organic extracts were dried over Na2S04, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (petroleum ether/EtOAc = 500/1 to 200/1 to 100/1) to give the title compound 3,5-dimethoxy-1,1'-biphenyl I22 (5.2 g, 100 %) as a white solid. LCMS-A (ES-API): Rt 2.47 min; m/z 215.0 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In N,N-dimethyl-formamide; at 80℃; for 60h;Inert atmosphere; | A 200-mL two-neck round-bottom flask was charged with anitrogen atmosphere, and to the flask, 1-bromo-3,5-dimethoxybenzene (2.92 g, 13.82 mmol), bis(pinacolato)diboron (5.26 g, 20.73 mmol), Pd(dppf)Cl2?CH2Cl2 (1.56 g, 1.91 mmol) and KOAc (2.10 g, 20.73 mmol) were added into 80 mL of dry DMF. The mixture was stirred at 80C for 60 h under nitrogen. Then, DMF was removed by vacuum distillation, and the residue was extracted with CH2Cl2 (3 20 mL). The CH2Cl2 layer was washed with H2O (2 x 20 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo to give a brown crude. The crude product was purified by column chromatography on silica gel (eluent: EtOAc: hexane, 2/3 v/v) to give white compound as a first band. (1.16 g, 88%). 1H-NMR (500 MHz, DMSO) delta(ppm)= 6.95(2H, d, J= 2.6 Hz), 6.57 (1H, t, J= 2.5 Hz), 3.81 (6H, s), and 1.34 (12H, s). |
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In N,N-dimethyl-formamide; at 90℃; for 39h;Inert atmosphere; | To a solution of 30 ml of anhydrous DMF, 1.29 g, 5 lf of dicarboxylidene diboron (1-bromo-3,5-dimethoxybenzene with frequency The molar ratio of the Ershou Er shed was 1: 1 ? 1, 0.69 g, 6.99 mmol of KOAc, 0.59 g, and 0. 69 mmol of PdCl2 (dppf) CH2C12 was added and stirred at 90 C for 39 hours. The resulting solution was distilled off under reduced pressure except that CH2C12 extracted the organic phase and Na2S04 was removed Water and distilled under reduced pressure to give the crude product. The crude product was purified by column chromatography. The stationary phase uses a sphere of 63 ~ 210mupi The mobile phase consisted of 40/6 (^ (012) 03013), and the column size was 7.511. The purified product was purified to give a white product. MS (MALDI-T0F, CH2C12): pi / zeta = 265.09, [M] Calculated value 265.1641, M = Ci4H2iB4.500MHz, DMSO): delta (ppm) = 6 ? 95 (2H, d, J = 2.6Hz), 6 ? 57 (1H, t, J = 2.5 Hz), 3.81 (6H, s), 1.34 (12H, s) | |
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In N,N-dimethyl-formamide; at 80℃; for 39h;Inert atmosphere; | Under a nitrogen atmosphere,2.92 g, 13.82 mmol of 1-bromo-3,5-dimethoxybenzene was dissolved in 80 ml of dry DMF,Continuous addition of 3.86g,15.20 mmol of pinacol diboron,2.10 g, 20.73 mmol KOAc,1.56 g, 1.91 mmol PdCl2 (dppf) · CH2Cl2,The mixture was stirred at 80 C for 39 hours,The resulting solution was distilled under reduced pressure to remove DMF,CH2Cl2 extraction of organic phase,Na2SO4 dehydration,After distillation under reduced pressure by column chromatography.The stationary phase was a spherical silica gel of 63 to 210 m,The EtOAc / CH3 (CH2) 4CH3 solution with a fixed phase diameter of 7.5 cm in height of 8 cm and a mobile phase of 40/60,The purified white material was purified by column chromatography with 2.18 g of 5.22 mmol of 4-bromo-2,6-bis [2- (1-methyl) benzimidazolyl] pyridine in 60 ml of anhydrous DMF,2.79 g, 28.46 mmol KOAc,0.87 g, 1.06 mmol PdCl2 (dppf) · CH2Cl2,The mixture was stirred at 80 C for 60 hours,The resulting solution was distilled under reduced pressure to remove DMF,CH2Cl2 extraction of organic phase,Dehydration of Na2SO4, distillation under reduced pressure by column chromatography,The stationary phase was a spherical silica gel of 63 to 210 m,Fixed phase diameter of 7.5cm height of 8cm,The mobile phase consisted of 60/40 EtOAc / CH3 (CH2) 4CH3 solution,The white intermediate 1 purified by column chromatography was dissolved in 50 ml of anhydrous CH2Cl2,In the ice bath slowly drip 1.0M, 15ml, 15mmol of BBr3 (dropping time 30min)After completion of the dropwise addition, the temperature was gradually raised to room temperature for 12 hours,The resulting solution was quenched by the dropwise addition of 20 ml of water in an ice-water bath,The aqueous phase was adjusted to pH to neutral and the organic phase was extracted with EtOAc.After washing with water, Na2SO4 was dehydrated, distilled under reduced pressure and washed with Hex. After filtration, the white intermediate 2 was recrystallized from DMSO / H2O and dissolved with 1.50 g of 4.45 mmol of 1- (4-bromobutyl) -pyrene 60 ml of DMF solution,1.52 g, 11.05 mmol of K2CO3 was added and stirred at 80 C for 90 h. The organic phase was extracted by distillation under reduced pressure. The organic phase was extracted with CH2Cl2 and dehydrated with Na2SO4. After distillation under reduced pressure, the column was purified by column chromatography using a spherical silica gel of 63 to 210 m A mixed solution of 30/70 EtOAc / CH2Cl2 with a diameter of 7.5 cm and a mobile phase of 30 cm and a mobile phase was purified by column chromatography to give the product Py2G1MeBip as a white product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.2% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 85℃; for 12h;Inert atmosphere; | 2.171 g of 1-bromo-3,5-dimethoxybenzene and 3.810 g of boronic acid pinacol ester were dissolved in 85 ml of dioxane,2.945 g of potassium acetate and 0.732 g of [1,1'-bis (diphenylphosphino) ferrocene] palladium dichloride were added, and the temperature was raised under argonTo 85 C, stirring for 12 hours after the stop heating, the reaction solution, a small amount of ethyl acetate washing cake, the filtrate concentrated evaporated, residualThe residue was chromatographed (petroleum ether: ethyl acetate = 99: 1-98: 2, V / V) to give 2.462 g of a white solid in 93.2% yield. |
85% | With bis-triphenylphosphine-palladium(II) chloride; triethylamine; In 1,2-dichloro-ethane; at 90℃; for 4h;Inert atmosphere; | As follows are specific steps of: adding 3,5-dimethoxy-bromobenzene (1.74 g, 8.0 mmol, 1.0 equivalent (hereinafter referred to as ?eq?)) and a catalyst PdCl(PPh)(281 mg, 0.4 mmol, 0.05 eq) into a 100 mL Schlenk reaction flask; performing a cycle of vacuumizing and filling nitrogen gas in the flask for three times; adding dried and redistilled 1,2-dichloroethane (20 ml), triethylamine (7 ml, 40 mmol, 5.0 eq) and pinacol borane (HBpin) (3.5 ml, 24.0 mmol, 3.0 eq) into the reaction flask by a syringe; heating the reaction system to 90 C. and performing a reflux reaction for 4 hours; cooling the reaction system down to room temperature, then pouring the reaction solution into 20 ml water to terminate the reaction; extracting aqueous phases with ethyl acetate for several times and combining organic phases; washing the organic phases with a saturated saline solution and water for one time, respectively; drying with anhydrous magnesium sulfate and spin-drying the solvent; recrystallizing an obtained product in n-hexane/ethyl acetate to obtain a 1.8 g white solid with the yield of 85%. H NMR (400 MHz, CDCl) delta (ppm) 7.03 (s, 2H, benzene), 6.90 (s, 1H, benzene), 3.84 (s, 6H, -OCH3), 1.33 (s, 12H, -CH3). |
85% | With bis-triphenylphosphine-palladium(II) chloride; triethylamine; In 1,2-dichloro-ethane; at 90℃; for 4h;Schlenk technique; Inert atmosphere; | 3,5-Dimethoxybromobenzene (1.74 g, 8.0 mmol, 1.0 eq) was added to a 100 mL Schlenk reaction flask,And the catalyst PdCl2 (PPh3) 2 (281 mg, 0.4 mmol, 0.05 eq)Repeat the vacuum - nitrogen three times,Dry re-distilled 1,2-dichloroethane (20 ml) was added to the reaction flask with a syringe,Triethylamine (7 ml, 40 mmol, 5.0 eq)And panthenol borane(HB pin) (3.5 ml, 24.0 mmol, 3.0 eq),The reaction system was heated to 90 C and refluxed for 4 h.The reaction was cooled to room temperature and the reaction mixture was poured into 20 ml of water to terminate the reaction. The aqueous phase was extracted several times with ethyl acetate. The combined organic phases were washed once with saturated brine and once with water, dried over anhydrous magnesium sulfate, And the resulting product was recrystallized from n-hexane / ethyl acetate to give 1.8 g of a white solid in 85% yield |
85% | With bis-triphenylphosphine-palladium(II) chloride; triethylamine; In 1,2-dichloro-ethane; at 90℃; for 4h;Schlenk technique; | The reaction mixture was prepared by adding 3,5dimethoxybromobenzene(1.74 g, 8.0 mmol, 1.0 eq) and catalyst PdCl2(PPh3) 2 (281 mg, 0.4 mmol, 0.05 eq) in a 100 mLSchlenk reaction flask, (20 ml), triethylamine (7 ml, 40 mmol, 5.0 eq) andcotaxyl borane (HBpin) were added to the reaction flask by means of a syringe, (3.5ml, 24.0mmol, 3.0eq), the reaction systemwas heated to 90 C and refluxed for 4 h. The reaction was cooled to room temperature and the reaction solution was pouredinto 20 ml of water to terminate the reaction. The aqueous phase was extracted with ethyl acetate several times. The organicphases were combined and washed once with saturated brine and water, dried over anhydrous magnesium sulfate, And theresulting product was recrystallized from nhexane/ ethyl acetate to give 1.8 g of a white solid in 85% yield. (S, 2H, benzene),6.90 (s, 1H, benzene), 3.84 (s, 6H, OCH3),1.33 (s, 12H, CH3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76.8% | With tris-(dibenzylideneacetone)dipalladium(0); potassium tert-butylate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 100 - 108℃; for 8h;Inert atmosphere; | The reaction route is as follows:250 mL three neck flask was added 2.41 g (9.0 × 10 -3 mol)1,1-bis (4-aminophenyl) cyclohexane,8.84 g (0.041 mol) of 3,5-dimethoxybromobenzene,5.08 g (0.045 mol) potassium tert-butoxide,48.2 g toluene.Under nitrogen atmosphere, 0.331 g (3.6 x 10-4 mol) of Pd2 (dba) 3,0.210 g (7.2 × 10 -4 mol) (t-Bu) 3PH · BF 4,The temperature was raised to 100 C to 108 C and refluxed for 8 hours.Completed the reaction,Add 50g water twice,Dried over anhydrous sodium sulfate,Decompression solvent was brown viscous liquid.The above crude product was treated with THF,Ethyl acetate (mass ratio of 5: 5) recrystallization,5.6g white powder was obtained,Yield: 76.8%. |
Tags: 20469-65-2 synthesis path| 20469-65-2 SDS| 20469-65-2 COA| 20469-65-2 purity| 20469-65-2 application| 20469-65-2 NMR| 20469-65-2 COA| 20469-65-2 structure
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Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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