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CAS No. : | 585-76-2 |
Formula : | C7H5BrO2 |
M.W : | 201.02 |
SMILES Code : | O=C(O)C1=CC=CC(Br)=C1 |
MDL No. : | MFCD00002487 |
InChI Key : | VOIZNVUXCQLQHS-UHFFFAOYSA-N |
Pubchem ID : | 11456 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | 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 |
---|---|---|
100% | With thionyl chloride; at 90℃; for 3h; | To a solution of 3-bromobenzoic acid (1.0 g, 5.0 mmol) in MeOH (20 mL) was addedSOC12 (5 mL) at room temperature and the resulting mixture was then stirred at 90 C for 3 hours. After the reaction was completed, the mixture was concentrated in vacuo to give methyl 3- bromobenzoate (1.1 g, quant.) as a colorless oil, which was used in next step directly without further purification. MS obsd. (ESIj [(M+H)]: 215.1&217.1. |
98% | To a reaction system equipped with an exhaust gas absorption device, m-bromobenzoic acid (200 g) Thionyl chloride 200g,70 degrees reaction 5h,After the reaction is completed, unreacted thionyl chloride is recovered;Under an ice bath, acid chloride was added dropwise to a solution of 200 g of methanol containing 84 g of sodium bicarbonate,The reaction was stirred for 2h, the reaction was stirred at room temperature for 2h;After the reaction was completed, the methanol was recovered under reduced pressure, 300 ml of water was added to the residue overnight, the mixture was extracted with methylene chloride, dried over anhydrous sodium sulfate,Filtering, recovering the solvent under reduced pressure;Petroleum ether: ethyl acetate = 5: 1;Recrystallization to give a light yellow solid 208g, yield 98%; | |
86% | With thionyl chloride; at 70℃; for 12h; | Step 1 Methyl 3-bromobenzoate: Thionyl chloride (12 g, 100.84 mmol) was added dropwise over a period of about 10 minutes to a solution of 3-bromobenzoic acid (10 g, 49.75 mmol) and methanol (100 ml). The solution was stirred at about 70 C. for about 12 hours, concentrated in vacuo, and water (100 ml) added to the resulting residue. Standard extractive workup with ethyl acetate (50 ml*3) gave the title product (9.2 g, yield=86%), which was used in the next step without any further purification. |
With glycerol-based sulfonic acid functionalized carbon catalyst; for 6h;Reflux; Green chemistry; | General procedure: To a stirred solution of substituted aryl carboxylic acid 1 (0.15 mol) in methanol (0.75 mol) glycerol-based solid acid catalyst (28 wt% of aryl carboxylic acid) was added and heated to reflux for 6 h. After completion of the reaction as indicated by TLC, the reaction mixture was cooled to room temperature. The catalyst was separated by filtration and was washed with methanol for recycle. Methanol was then distilled off under reduced pressure to get the pure methyl ester 2. | |
With thionyl chloride; at 0 - 62℃; for 16h;Inert atmosphere; | To a mixture of 3-bromobenzoic acid (85.0 g, 423 mmol) in methanol (700 mL) was added thionyl chloride (151 g, 1.27 mol) dropwise at rt under nitrogen atmosphere. The mixture was stirred at 62 C for 16 hours. On completion, the reaction was concentrated in vacuo to give a residue. The residue was washed with saturated sodium bicarbonate (100 mL) and extracted with dichloromethane (2 X 100 mL). The organic layer was dried over sodium sulfate, concentrated in vacuo to give the title compound. ‘H NIVIR (400MHz, CDC13) = 8.21 (s, 1H), 8.09 - 7.90 (m, 1H), 7.78 - 7.61 (m, 1H), 7.46 - 7.21 (m, 1H), 3.97 (s, 3H). | |
With thionyl chloride; at 40℃; for 1h; | General procedure: To a solution of 5.0 mmol of dierent substituted benzoic acids (1a~1p, 1s, and 1t), nicotinic acid(1q) or 2-phenylacetic acid (1r) in MeOH (15 mL) was added sulfurous dichloride (2 mL), then the mixture was allowed to reach 40 C and stirred for 1 h. The resulting solution was concentrated andpartitioned between sodium bicarbonate solution (PH 7~8) and ethyl acetate (3). The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated to yield the correspondingesters (2a~2t) in 89%-96% yields, which were taken up for the next step without any purification. | |
With sulfuric acid; for 8h;Reflux; | General procedure: The substituted benzoic acid 11q (1 eq.) in methanol was refluxed for 8h. The reactions were completed monitored by TLC (PE/EA=3:1). Then cooling to rt, the solution was adjusted to pH=7 with NaOH. The mixture was extracted with ethyl acetate and washed with brine to give the crude product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | General procedure: Bromobenzoic acid (0.5 g, 2.49 mmol) andpalladium acetate (1.15 mg, 0.005 mmol, 0.1 mol %) weredissolved in 15 ml of water under an argon atmosphere. After stirring for5 min at RT, p-tolylboronic acid (0.36 g,2.61 mmol) and KOH (0.42 g, 7.47 mmol) were added and it washeated to reflux for 5h. After cooling to RT, it was acidified with HCl and theproduct was extracted three times with methylene chloride. The combined organiclayers were dried over Na2SO4 and the solvent wasevaporated in vacuo. The crude product was purified by column chromatography onsilica gel with methylene chloride/methanol (9:1). | |
96% | With potassium carbonate; In water; at 20.0℃; for 4h;Green chemistry; | General procedure: A 50 mL flask was charged with an aryl halide (1.0 mmol), anaryl boronic acid (1.2 mmol), K2CO3 (2.0 mmol), nanocatalyst(0.05 mol% Pd) and deionized water (5 mL). The reactionwas stirred at room temperature for 4 h. The progress ofthe reaction was monitored by thin-layer chromatography After the reaction was completed, distilled water (25 mL) wasadded to the mixture and dilute 2 mol/L HCl was added dropwiseto pH 3.0-4.0 with stirring, and the mixture was heatedto 100 C for 10 min. The white solid that had formed wasfiltered off and washed with hot water. After drying, it wasdissolved in ether (5 mL) and was rapidly separated using asilica gel column. Elution with ether left behind small amountsof impurities and traces of palladium black to give a crudeproduct. The ether solution was evaporated to 3-5 mL andrecrystallized to obtain a pure product. All the products 3a-uare known compounds and were characterized by comparingtheir melting points and 1H NMR spectra with those preparedrecently by using a water-soluble glycine-based Pd catalyst,PdCl2(NH2CH2CO2H)2.10 The melting points and 1H NMRdata of 3a-u are listed in the supplemental material. |
80% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 100.0℃; for 4h; | General procedure: 3-bromobenzoic acid, the required aryl boronic acid (1.1 eq), K2CO3 (3 eq) and palladium(0) tetrakis(triphenylphosphine) are given in a screw-cap reactor, a 8:8: 1 toluene/EtOH/H2O mixture (8.5 mL/mmol 3-bromobenzoic acid) is added, the reactor is closed tightly and heated to 100C under stirring. After 4 h the mixture is cooled to room temperature, diluted with AcOEt (10 mL/mmol 3-bromobenzoic acid) and extracted with 5 % NaHCO3 (4x 10 mL/mmol 3-bromobenzoic acid). The pooled basic extracts are acidified to pH 3 by dropwise addition of concentrated HCI under stirring, then extracted with AcOEt (3x 10 mL/mmol 3-bromobenzoic acid). The pooled organic extracts are washed with water (10 mL/mmol 3-bromobenzoic acid) and brine (10 mL/mmol 3-bromobenzoic acid), dried over Na2SO4, filtered and evaporated to dryness under reduced pressure. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; triethylamine; In tetrahydrofuran; tert-butyl alcohol; | a 3-Bromo-benzoic Acid Tert-butyl Ester 2,4,6-Trichlorobenzoic acid (11.7 ml, 75 mmol) was added dropwise to a solution of 3-bromobenzoic acid (15 g, 75 mmol), triethyl amine (10.5 ml, 75 mmol) in THF (25 ml) at RT. The reaction was stirred 15 min. Then, t-butanol (7.1 ml, 150 mmol) and DMAP (18.3 g, 150 mmol) were added and the reaction was stirred overnight. The crude reaction was filtered through a pad of silica gel, concentrated, and was used in the next reaction without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With sulfuric acid; In methanol; dichloromethane; ethyl acetate; | Part A: 3-Bromobenzoic acid (1.1 g, 5.47 mmol) was dissolved in methanol (20 ml) in a 50 ml flask. Concentrated sulfuric acid (2 drops) was added and the mixture was refluxed under nitrogen for ten hours then concentrated under reduced pressure. The residue was mixed with dichloromethane (20 ml) and saturated sodium bicarbonate solution (10 ml). The organic material was separated, dried (MgSO4) and concentrated under reduced pressure. The residue was flushed through silica gel with hexane/ethyl acetate (3:1), and concentrated which provided methyl 3-bromobenzoate (1.0 g, 85%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With silver(I) acetate;palladium diacetate; In acetic acid; at 120℃; for 5.5h; | Palladium acetate (11.4 mg 0.05 mmol), AgOAc (217 mg 1.3 mmol), 3-bromobenzoic acid (201 mg, 1.0 mmol), <strong>[3032-81-3]3,5-dichloroiodobenzene</strong> (819 mg, 3.0 mmol) and acetic acid (200 muL) were combined and heated at 120° C. for 5.5 h. After purification light tan solid was obtained, 183 mg (53percent), mp 182-186° C. (isooctane). Rf-0.38 (1/9 ethyl acetate-dichloromethane). 1H NMR (300 MHz, acetone-d6) delta 7.32 (br s, 2H), 7.36 (d, J-8.4 Hz, 1H), 7.44 (br s, 1H), 7.79 (d, J-8.4 Hz, 1H), 8.05 (br s, 1H). Carboxylate proton signal was not observed. 13C NMR (75 MHz, acetone-d6) delta 122.2, 127.6, 127.7, 133.2, 133.3, 134.6, 135.0, 139.4, 144.5, 166.7. A signal for one aromatic carbon could not be located. FT-IR (neat, cm1) upsilon 1699, 1299, 857. Anal. calcd for C13H7BrCl2O2 (346.00 g/mol): C, 45.13; H, 2.04. Found: C, 45.17; H, 2.04. The 1H NMR and 13C NMR spectra are shown in FIGS. 27AB, respectively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | Example 1 3-[(3-Bromophenyl)carbonyl]amino}pyridine-4-carboxylic acid (A-1)3-Bromobenzoic acid (16.39 g, 81 mmol), EDC (16.65 g, 87 mmol), HOAT (13.30 g, 87 mmol), and DIEA (20.2 mL, 116 mmol) were dissolved in 500 mL of DMF and stirred at room temperature. After 30 minutes, 3-aminoisonicotinic acid (8 g, 57.9 mmol) was added. After 10 hours, the solvent was removed by rotary evaporation and then triturated with 100 mL water. After sonication, the solids were filtered off and dried under vacuum to yield 15.2 g (87%) of A-1 as a tan solid. Data for A-1: LRMS m/z (M+H): 304.64. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dihydrogen peroxide; N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid;pH 7.4;Kinetics; | A series of compounds were synthesized and kinetically analyzed (Table 1). The measured rate constants correlate well with the Hammett ? parameters giving a p value of 3.80 (Figure 4). Many of the compounds display faster reactivity with Eta202 than BFA. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In acetonitrile; at 90℃; for 2h;Inert atmosphere; | A degassed mixture of 3-bromobenzoic acid (CAS 585-76-2) (1 g, 4.97 mmol), 3-((tert- butoxycarbonylamino)methyl)phenylboronic acid (CAS 8321 14-05-3) (1.249 g, 4.97 mmol), PdCI2(dppf).CH2CI2 adduct (CAS 95464-05-4) (0.203 g, 0.249 mmol), and 2M aq. K3P04 (7.46 ml, 14.92 mmol) in CH3CN (25 ml.) was heated at 90 C for 2 hr. The reaction mixture was diluted with EtOAc and washed with water. The aqueous layer was extracted with EtOAc. The combined organics were washed with brine, dried (Na2S04) and concentrated. The residue was purified by FCC (EtOAc-heptane 0-100%) to provide the title compound. MS (ESI ) m/z 326.2 (M-H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; HATU; In N,N-dimethyl-formamide; at 20℃; for 0.5h;Inert atmosphere; | TEA (0.276 ml_, 1 .984 mmol) was added to a mixture of 3-bromobenzoic acid (199 mg, 0.992 mmol) and HATU (415 mg, 1 .091 mmol) in DMF at 23 C. In a separate vial, methyl 2-(2- aminophenyl)acetate hydrochloride (CAS 49851 -36-7) (200 mg, 0.992 mmol) was stirred with TEA (0.276 ml_, 1 .980 mmol) in DMF (0.5 ml_). After 5 min, the solution of methyl 2-(2- aminophenyl)acetate hydrochloride (200 mg, 0.992 mmol) was added to the 3-bromobenzoic acid (199 mg, 0.992 mmol) mixture and the resulting mixture was stirred at rt for 30 min. The reaction mixture was diluted with EtOAc and washed with water. The aqueous layer was extracted with EtOAc. The combined organics were washed with 5% aq LiCI, dried (Na2S04) and concentrated. The resulting residue was purified by silica gel chromatography (EtOAc- heptanes 0-60%) to provide the title compound. MS (ESI+) m/z 348.0, 350.0 (M+H). | |
With triethylamine; HATU; In N,N-dimethyl-formamide; at 23℃; for 0.583333h; | Intermediate 36. Methyl 2-(2-(3-bromobenzamido)phenyl)acetate TEA (0.276 ml_, 1 .984 mmol) was added to a mixture of 3-bromobenzoic acid (199 mg, 0.992 mmol) and HATU (415 mg, 1 .091 mmol) in DMF at 23 C. In a separate vial, methyl 2-(2- aminophenyl)acetate hydrochloride (CAS 49851 -36-7) (200 mg, 0.992 mmol) was stirred with TEA (0.276 ml_, 1 .980 mmol) in DMF (0.5 ml_). After 5 min, the solution of methyl 2-(2- aminophenyl)acetate hydrochloride (200 mg, 0.992 mmol) was added and the resulting mixture was stirred at room temperature for 30 min. The reaction mixture was diluted with EtOAc and washed with water. The aqueous layer was extracted with EtOAc. The combined organics were washed with 5% aq LiCI, dried (Na2S04) and concentrated. The resulting residue was purified by silica gel chromatography (EtOAc- heptanes 0-60%) to provide the title compound. MS (EST) m/z 348.0, 350.0 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With bis-triphenylphosphine-palladium(II) chloride; potassium phosphate; In 1,4-dioxane; water; at 95℃;Inert atmosphere; | General procedure: The halo aryl (1.0 equiv) was dissolved in a mixture of water:dioxane (1:1). The boronic acid or ester(1.5 equiv) and potassium phosphate (5.0 equiv) were added. The solution was degassed byvacuum/argon cycles (10 times) before addition of PdCl2(PPh3)2 (10 mol%) and further degassed (5times). The resulting mixture was stirred at 95 C under argon atmosphere for 16-20 hours. Thereaction mixture was filtered through Celite and diluted with water (approx. 30 mL) before washingwith chloroform (3 x 30 mL). If not stated otherwise, the aqueous phase was concentrated underreduced pressure and applied to a C18 precolumn before purification on a 10g or 60 g C18 column witha gradient of acetonitrile in water (10-100%) to yield the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; cesium fluoride; In 1,2-dimethoxyethane; at 80℃; for 9h;Schlenk technique; Inert atmosphere; | In an inert Schlenk flask, 500 mg (2.49 mmol, 1.00 eq) 3-bromobenzoic acid, 413 mg (2.49 mmol, 1.00eq) 4-ethoxyphenylboronic acid, 1.17 g (7.72 mmol, 3.10 eq) CsF and 102 mg (124 μmol, 0.05 eq)PdCl2(dppf)*DCM were suspended in 20.0 mL anhydrous DME. The orange suspension was degassedby vacuum/N2 cycles and stirred at 80 C for 9 h. TLC analysis (DCM/MeOH 9:1) indicated fullconversion of the starting material. The reaction mixture was hydrolyzed with 6 mL 5% HCl solution,extracted with EtOAc (2 x 5 mL) and the combined organic layers were dried over MgSO4. The solventwas removed under reduced pressure and final purification by column chromatography (DCM/MeOH20:1, size: 17.0 x 2.0 cm, 25 g silica gel) yielded the pure product as brown solid (577 mg, 96 %). |
Tags: 3-Bromobenzoic acid | Bromides | Carboxylic Acids | Aryls | Fluorinated Building Blocks | Organic Building Blocks | 585-76-2
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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 |
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