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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Synonyms: 4-Methoxycarbonylbenzeneboronic acid
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Campbell, Allea ; Alsudairy, Ziad ; Dun, Chaochao ; Akram, Fazli ; Smith-Petty, Kayla ; Ambus, Abrianna , et al.
Abstract: Covalent organic framework (COF)-supported palladium catalysts have garnered enormous attention for cross-coupling reactions. However, the limited linkage types in COF hosts and their suboptimal catalytic performance have hindered their widespread implementation. Herein, we present the first study immobilizing palladium acetate onto a dioxin-linked COF (Pd/COF-318) through a facile solution impregnation approach. By virtue of its permanent porosity, accessible Pd sites arranged in periodic skeletons, and framework robustness, the resultant Pd/COF-318 exhibits exceptionally high activity and broad substrate scope for the Suzuki-Miyaura coupling reaction between aryl bromides and arylboronic acids at room temperature within an hour, rendering it among the most effective Pd/COF catalysts for Suzuki-Miyaura coupling reactions to date. Moreover, Pd/COF-318 demonstrates excellent recyclability, retaining high activity over five cycles without significant deactivation. The leaching test confirms the heterogeneity of the catalyst. This work uncovers the vast potential of dioxin-linked COFs as catalyst supports for highly active, selective, and durable organometallic catalysis.
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Keywords: covalent organic framework (COF) ; dioxin-linked COF ; Pd(II) immobilization ; Suzuki-Miyaura coupling
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Purchased from AmBeed: 24067-17-2 ; 98-80-6 ; 3375-31-3 ; 71597-85-8 ; 4877-80-9 ; 99768-12-4
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CAS No. : | 99768-12-4 |
Formula : | C8H9BO4 |
M.W : | 179.97 |
SMILES Code : | O=C(C1=CC=C(B(O)O)C=C1)OC |
Synonyms : |
4-Methoxycarbonylbenzeneboronic acid
|
MDL No. : | MFCD01632203 |
InChI Key : | PQCXFUXRTRESBD-UHFFFAOYSA-N |
Pubchem ID : | 2734369 |
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 |
---|---|---|
97% | With C54H74Cl2N4O2Pd2; In ethanol; at 22℃; for 6h; | Reaction flask (10 mL) equipped with stirring bar was charged with (4-(methoxycarbonyl)phenylboronic acid (66 mg, 0.91 mmol), ethanol (96%) (2 mL), [{Pd(mu-OH)Cl(IPr)}2] (5 10-4 g, 4.55 × 10-7 mol). Reaction mixture was stirred at 22 C for 6 h. Aftercompletion of the reaction solvent was evaporated, the residue was dissolved in hexane (5 mL) andextracted with water (2 × 2 mL). The organic layer was dried over magnesium sulphate, and hexanewas evaporated under reduced pressure. 96 mg of dimethyl[1,1'-biphenyl]-4,4'-dicarboxylate wasobtained as a white solid. Yield = 97%. 1H NMR (403 MHz, CDCl3, ppm) delta: 8.13 (d, J = 8.7 Hz, 4H),7.69 (d, J = 8.7 Hz, 4H), 3.95 (s, 6H); 13C NMR (101 MHz, CDCl3, ppm) delta: 166.79, 153.16, 144.34,130.19, 129.68, 127.23, 124.20, 52.2. MS (EI) m/z (%) = 270 (M+, 48), 255 (11), 239 (100), 211 (9),209 (8), 153 (10), 152 (11), 59 (10). |
95% | With Cu2(ophen)2; In N,N-dimethyl-formamide; at 20℃; for 20h; | General procedure: 4.3. Catalytic tests: general procedure I for the Cu2(ophen)2catalyzed homocoupling for Table 2 A solution of the corresponding arylboronic acids (1.0 mmol),Cu2(ophen)2 (1.3 mg, 0.5 mol %), DMF (1.0 mL) in 5 mL round-bottomed ask was stirred under air and the reaction was moni-tored by TLC. After the substrate was consumed, the reaction con-versions were determined bygas chromatography (GC) analysis (FIDfrom AGILENT 7820) using a cross-linked (95%)-dimethyl-(5%)-diphenylpolysil-oxane column (HP-5, 30 m0.32 mm0.25 mm),helium, injector temperature 250 C, detector temperature 300 C,and oven temperature program 45 C (3 min)e20C/mine280 C(2 min). The resulting mixture was poured into brine (10 mL), andextracted with diethyl ether (310 mL). The organic layer waswashed with brine, dried over Mg2SO4, the residue was chromato-graphed via a short column of silica gel (petroleum ether: diethylether15:1) and evaporated under reduced pressure. The productswas determined by 1H NMR spectroscopy. All 1H NMR spectra weremeasured in CDCl3 with TMS as the internal standard. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; for 18h;Heating / reflux; | Procedure M: A suspension of <strong>[34259-99-9]<strong>[34259-99-9]4-bromothiazol</strong>e</strong> (1.13 g, 6.89 mmol), 4-methoxycarbonylphenylboronic acid (1.85 g, 10.3 mmol) and Tetrakis (triphenylphosphine) palladium (0) (0.35 g, 0.30 mmol) in dioxane (45 mL) and 2M Na2CC>3 (17.2 mL) is heated to reflux for 18h. The reaction is allowed to cool and filtered. The filtrate is evaporated in vacuo, and the residue is dissolved in ethyl acetate and washed with water (2X) and brine (2X). The combined organic layers are dried over Na2S04, and concentrated in vacuo. The crude material is purified by flash chromatography (100percent hexanes - 40percent ethyl acetate/hexanes) to give 4-thiazol-4-yl-benzoic acid methyl ester as a white solid (0.68g, 45percent) MS (ES+) 220.2 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; ethanol; at 80 - 90℃; for 8 - 48h; | General Procedure A: Suzuki type coupling AA mixture of the aryl halide (1 eq,), the boronic acid or boronic ester (1.1-1.2 eq.), tetrakis (triphenylphosphine) palladium (0) (0.05-0.leq.), and 2M Na2C03 (2.2 eq.) in 0-20 %EtOH/ dioxane (degassed by vacuum, then N2 purge) is stirred 8-48 hours at 80-90 C.Reaction is allowed to cool, diluted with an organic solvent, eg. CH2CI2 or EtOAc,washed with aq. NaHC03 and brine, dried (Na2SC>4) and concentrated in vacuo. Thecrude mixture is purified by chromatography to give the desired product.; General Procedure C: Methyl Ester HydrolysisA mixture of the methyl ester and lithium hydroxide monohydrate is stirred in 10-25 %aqueous dioxane or 10-25 % aqueous tetrahydrofuran for 4-96 hours until the methylester is consumed. The reaction mixture is concentrated and dried in vacuo. Thecarboxylic acid lithium salt is used without further purification or is converted to thecarboxylic acid by adding H2O, washing with diethylether, adjusting the aqueous layerpH to ~ 2.0 with 1 N HC1, then filtering and drying the free acid in vacuo.; Intermediate Preparation 6 4-(5-Sulfamoyl-thiophen-2-yl)-benzoic acid, lithium saltThe title intermediate is prepared in a manner substantially analogous General Procedure A, followed by General Procedure C using of the 5-Bromo-thiophene-2-sulfonic acid amide (CAS 53595-65-6) and 4-methoxycarbonylphenyl boronic acid to give the desired intermediate. (180 mg,) MS (ES-) 282.0 (M-H)" |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 150℃;Microwave irradiation; | 2-Chloro-quinoline-4-carboxylic acid (0.23 g, 1.4 mmol) was dissolved in dioxane (5 mL) and (4-methoxycarbonylphenyl)boronic acid (0.39 g, 2.2 mmol), Pd(PPh3)4 (0.20 g, 0.17 mmol) and K2CO3 (0.73 g, 5.3 mmol) were added. The reaction mixture was degassed, sealed, and heated in the microwave at 150 0C for 30 min. The reaction mixture was filtered and concentrated in vacuo to leave a residue. The residue was purified by flash column chromatography, using a 1:2 mixture of EtO Ac/heptane with 1percent acetic acid as eluent, to give the title compound (0.23 g, 53percent). m/z 308.06 (M+H)+. |
53% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 150℃; for 0.5h;Inert atmosphere; Microwave irradiation; | 2-Chloro-6-methylisonicotinic acid in place of 2-bromoisonicotinic acid. 2-Chloro-quinoline-4-carboxylic acid (0.23 g, 1.4 mmol) was dissolved in dioxane (5 mL) and (4-methoxycarbonylphenyl)boronic acid (0.39 g, 2.2 mmol), Pd(PPh3)4 (0.20 g, 0.17 mmol) and K2CO3 (0.73 g, 5.3 mmol) were added. The reaction mixture was degassed, sealed, and heated in the microwave at 150 °C for 30 min. The reaction mixture was filtered and concentrated in vacuo to leave a residue. The residue was purified by flash chromatography, using a 1:2 mixture of EtOAc/heptane with 1percent AcOH as eluent, to give the intermediate 2-[4-(methoxycarbonyl)phenyl]quinoline-4-carboxylic acid (0.23 g, 53percent). m/z 308.06 (M+H)+. TBTU (86 mg, 0.27 mmol) and N-methylmorpholine (39 mg, 0.38 mmol) were added to a solution of 2-[4-(methoxycarbonyl)phenyl]quinoline-4-carboxylic acid (29 mg, 0.10 mmol) in DMF (2 mL) and the reaction mixture was stirred at rt for 10 min. tert-Butyl [trans-4-(amino-methyl)cyclohexyl]methyl}carbamate (35 mg, 0.15 mmol) was then added and the reaction mixture was stirred at rt for 2 h. The reaction mixture was concentrated in vacuo to leave a residue, which was dissolved in DCM and washed with a saturated aq. solution of NaHCO3 and dried (phase separator). The mixture was concentrated in vacuo to leave a residue which was dissolved in DMSO and purified by HPLC using a gradient of 30-100percent mobile phase A (100percent CH3CN) over 30 min (mobile phase B = 5percent CH3CN + 95percent 0.1M NH4OAc) to give the intermediate methyl ester (12 mg, 24percent). m/z 530.32 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47% | With caesium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; water; at 105℃; for 16h;Inert atmosphere; | Example 40 Synthesis of methyl 4-(5-acetylfuran-2-yl)benzoate To a solution of <strong>[3199-50-6]1-(5-bromofuran-2-yl)ethanone</strong> (963 mg, 5.09 mmol) and cesium carbonate (4.98 g, 15.27 mmol) in water/dioxane (5%, 20 mL), flushed with nitrogen for 15 minutes, was added 4-methoxycarbonylphenyl boronic acid (1.01 g, 5.60 mmol), followed by catalyst PdCl2(dppf) (186 mg, 0.255 mmol). The solution was heated to reflux (105 C.) under nitrogen, for 16 hours. Water (50 mL) was added to the mixture after cooling to RT. Filtration gave 1.44 g of black crude material. Purification via silica column chromatography eluding with dichloromethane gave methyl 4-(5-acetylfuran-2-yl)benzoate (580 g, 2.37 mmol, 47% yield) as a yellow solid. LCMS (ES): m/z 245 [M+1]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
740 mg | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 100℃;Inert atmosphere; | Preparation Example 4 An aqueous solution (3 ml) of tetrakis triphenylphosphine palladium (115 mg) and sodium carbonate (530 mg) was added to a dioxane (20 ml) solution of <strong>[425379-16-4]2-bromo-3-fluorobenzonitrile</strong> (667 mg) and 4-(methoxycarbonyl)phenyl boronic acid (600 mg), followed by stirring overnight at 100 C. in an argon atmosphere, thereafter, cooling to room temperature, diluting with ethyl acetate, washing with saturated brine, and drying over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The solid of the crude product obtained was washed with diisopropylether and dried under reduced pressure, thereby obtaining methyl 2'-cyano-6'-fluorobiphenyl-4-carboxylate (740 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; silver trifluoroacetate; In methanol; at 60℃;Schlenk technique; Inert atmosphere; | General procedure: A mixture of N-pyrimidyl indoles 1 (0.20 mmol, 1.0 equiv.), arylboronicacids 2 (0.40 mmol, 2.0 equiv.),AgOOCF3 (0.80 mmol, 4.0 equiv.), and [RhCp*Cl2]2(0.002 mmol, 0.01 equiv.) were combined in MeOH (1.0 mL) in a dried Schlenk tubeunder a argon atmosphere. The resulting mixture was stirred at 60 C andmonitored by TLC. Uponcompletion or no further improvement of reaction, the reaction mixture wascooled to room temperature and added with Et3N (1 mL). Then themixture was filtered through a pad of silica gel eluting with 25 mL of CH2Cl2.The solvent was removed under reduced pressure and the residue was purified byflash chromatography on silica gel to afford the desired products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70%Chromat.; 25%Chromat. | With Cu2(ophen)2; water; In ethanol; at 20℃;Green chemistry; | General procedure: 4.4. General procedure II for Table 3 A solution of arylboronic acids (1.0 mmol), Cu2(ophen)2 (1.3 mg,0.5 mol percent) in H2O-EtOH (1.8 mL, VH2O:VEtOHn:1) was stirred atroom temperature. After the substrate was consumed, the reactionconversions were determined by GC analysis. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With bis-triphenylphosphine-palladium(II) chloride; sodium hydrogencarbonate; In tetrahydrofuran; water; for 4h;Inert atmosphere; Reflux; | The synthesis has been carried out differing from the literature procedure [15] . A mixture of 4-(methoxycarbonyl)boronic acid (2.04 g, 11.4 mmol) and methyl 4-iodobenzoate (3.00 g, 11.4 mmol) in 75 ml THF and 90 ml H2O was degassed (10 min) under an argon atmosphere followed by the addition of Pd(PPh3)2Cl2 (92.4 mg, 0.132 mmol) and NaHCO3 (9.00 g, 107.1 mmol). After refluxing for 4 h and cooling down to room temperature, the resulting crystalline solid was collected by vacuum filtration (fraction 1). The residue obtained by the evaporation of the filtrate was extracted with 200 ml CH2Cl2. Drying of the organic phase (Na2SO4) and evaporation of the solvent gave a white solid (fraction 2). The two fractions were combined and crystallized from toluene to yield 7 as a white flaky solid (1.96 g, 64percent). Mp: 211-212 °C (lit. 212-213 °C [39] ). 1H NMR (DMSO-d6): deltaH = 3.89 (s, CH3), 7.91 (d, Ar-H, J = 8.55 Hz), 8.07 (d, Ar-H, J = 8.55 Hz). 13C NMR (DMSO-d6): deltaC = 52.2 (CH3), 127.3, 129.2, 129.9, 143.2 (Ar-C), 165.9 (COOMe). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | With bis-triphenylphosphine-palladium(II) chloride; In acetonitrile; at 140℃; for 1.5h;Inert atmosphere; Microwave irradiation; | [0226] Intermediate 1-2 (266 mg), (4-(methoxycarbonyl)phenyl)boronic acid (150 mg), and (Ph3P)2PdCl2, (66 mg, catalyst) were mixed with 2mL acetonitrile and 2mL water in a microwave tube and degassed, and backfilled with argon. A 2-phase system resulted. This mixture was heated at 140 degrees (High) for 3600 sec, then another 1800 sec. The black and tarry looking reaction was filtered, partitioned with EtOAc and water, separated, and dried over magnesium sulfate. After chromatography, as above, 140 mg (44percent) light yellow 85percent pure methyl 5'-(lH-imidazol-l-yl)-2'-nitro-[l, -biphenyl]-4-carboxylate, 1-3, was obtained. (0457) GC/MS: 5.736min, 15percent, m/e: 270, 239(base), dimethyl [l,l '-biphenyl]- 4,4'- dicarboxylate (impurity) and 7.081min (85percent, m/e: 323, 292, 235), 1-3. |