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CAS No. : | 3597-91-9 | MDL No. : | MFCD00004660 |
Formula : | C13H12O | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | AXCHZLOJGKSWLV-UHFFFAOYSA-N |
M.W : | 184.23 | Pubchem ID : | 19186 |
Synonyms : |
|
Num. heavy atoms : | 14 |
Num. arom. heavy atoms : | 12 |
Fraction Csp3 : | 0.08 |
Num. rotatable bonds : | 2 |
Num. H-bond acceptors : | 1.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 58.01 |
TPSA : | 20.23 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) : | -5.02 cm/s |
Log Po/w (iLOGP) : | 2.32 |
Log Po/w (XLOGP3) : | 3.38 |
Log Po/w (WLOGP) : | 2.69 |
Log Po/w (MLOGP) : | 3.08 |
Log Po/w (SILICOS-IT) : | 3.42 |
Consensus Log Po/w : | 2.98 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 2.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.61 |
Solubility : | 0.0448 mg/ml ; 0.000243 mol/l |
Class : | Soluble |
Log S (Ali) : | -3.48 |
Solubility : | 0.0605 mg/ml ; 0.000329 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -4.74 |
Solubility : | 0.00332 mg/ml ; 0.000018 mol/l |
Class : | Moderately soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.36 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
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 |
---|---|---|
95% | With carbon tetrabromide; triphenylphosphine In dichloromethane at 20℃; for 1.5 h; | Carbon tetrabromide (8.99 g, 27.1 MMOL) and triphenyl phosphine (7.11 g, 27.1 MMOL) were added to a stirred solution of biphenyl-4-yl methanol (5.00 g, 27.1 MMOL) in dichloromethane (100 mL) at room temperature. Stirring was continued at room temperature for 1.5 hours then the solvent removed by evaporation under reduced pressure. The residue was purified by column chromatography on silica gel (1: 20 diethyl ether: cyclohexane) to give the title compound (6.37g, 95percent) as a white solid.'H NMR (400 MHz: CDCI3) : 7.6 (4 H), 7.45 (4 H), 7.35 (1 H), 4.55 (2 H). |
95% | With carbon tetrabromide; triphenylphosphine In dichloromethane at 20℃; for 1.5 h; | Carbon tetrabromide (8.99 g, 27.1 mmol) and triphenyl phosphine (7.11 g, 27.1 mmol) wereadded to a stirred solution of biphenyl-4-yl methanol (5.00 g, 27.1 mmol) indichloromethane (100 ml_) at room temperature. Stirring was continued at room temperaturefor 1.5 hours then the solvent removed by evaporation under reduced pressure. Theresidue was purified by column chromatography on silica gel (1:20 diethyl ether:cyclohexane) to give the title compound (6.37g, 95percent) as a white solid. 1H NMR (400 MHz:CDCI3): 7.6 (4 H), 7.45 (4 H), 7.35 (1 H), 4.55 (2 H). |
91% | With phosphorus pentoxide; potassium bromide In acetonitrile at 20℃; for 1 h; | General procedure: To a mixture of alcohol (1 mmol) and KBr (1.5 mmol, 0.18 g) in acetonitrile (5 mL), P2O5 (1.5 mmol, 0.23 g) was added and the reaction was stirred at room temperature for the time specified in Table 3. After reaction completion (TLC or GC), the reaction mixture was filtered and the residue washed with ethyl acetate (3 × 8 mL). The combined organic layers were washed with water (10 mL) and dried over Na2SO4. The solvent was removed under reduced pressure to afford the corresponding product. If necessary, further purification was performed by column chromatography. |
75% | With phosphorus tribromide In chloroform; di-isopropyl ether | Reference Example 50 4-Phenylbenzyl Bromide To a solution of 4-phenylbenzyl alcohol (1.00 g, 5.43 mmol) in a mixture of diisopropyl ether (10 mL) and chloroform (20 mL) was added phosphorus tribromide (0.98 g, 3.62 mmol) with ice-cooling and the mixture was stirred at room temperature for 1 hour. This reaction mixture was diluted with water and extracted with diisopropyl ether. The organic layer was washed with water and saturated aqueous sodium hydrogen carbonate solution, dried over MgSO4, and filtered. The filtrate was concentrated under reduced pressure and the residue was recrystallized from ethanol-hexane to provide 1.00 g of the title compound. Yield 75percent. m.p. 86-88° C. 1H-NMR (CDCl3) δ: 4.55 (2H, s), 7.32-7.67 (9H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With thionyl chloride In dichloromethane at 0℃; for 4h; Inert atmosphere; | |
86% | With tetra-(n-butyl)ammonium iodide; 1,2-dichloro-ethane; triphenylphosphine at 120℃; for 0.5h; Sealed tube; Inert atmosphere; | |
85% | With pyridine; thionyl chloride In diethyl ether at 0 - 20℃; for 12.5h; |
77.9% | With thionyl chloride In chloroform at 5 - 30℃; | |
74.6% | With hydrogenchloride In water at 90℃; for 0.333333h; | General procedure for the synthesis of 4-phenylbenzyl chloride and 3,5-dimethylbenzyl chloride General procedure: Concentrated hydrochloric acid was added to an appropriate substituted benzyl alcohol. The reaction mixture was heated in an oil bath at 90 °C for 20 minutes. After cooling, the mixture was extracted with hexane. The organic layer was separated and then washed with water (2 × 15 ml), 5 % sodium bicarbonate (1 × 15 ml) and brine (2 ×15 ml). The solution was dried over either calcium chloride or sodium sulfate. The solvent was removed in vacuo to give a substituted benzyl chloride. |
46% | With thionyl chloride; triethylamine In dichloromethane Inert atmosphere; | |
35% | With thionyl chloride In diethyl ether at 20℃; Inert atmosphere; | 5.1.1. Procedure adapted from Jaschinski and Hiersemann [87] 4-Biphenymethanol (1.020 g, 5.54 mmol) was dissolved inanhydrous ether (2 mL/mmol of alcohol). Thionyl chloride (0.80 mL,10.86 mmol) was added and the reaction mixture stirred at roomtemperature for 1e2 days. The reaction was quenched with water,and extracted twice with dichloromethane. The dichloromethanefractions were combined and washed with water, dried overmagnesium sulfate and concentrated under reduced pressure. Theresulting white solid was purified by column chromatograph (10%ethyl acetate in petroleum spirits 40-60 C) to afford the desiredproduct as a white solid (0.392 g, 35%). m.p. 71e73 C (68e69 C lit.[88]); 1H NMR (CDCl3) d 7.62e7.58 (4H, m), 7.49e7.44 (4H, m),7.40e7.35 (1H, m), 4.65 (2H, s); 13C NMR (CDCl3) d 141.6, 140.7,136.6, 129.2, 129.0, 127.69, 127.65, 127.3, 46.2. |
With hydrogenchloride at 100℃; im Rohr; | ||
With thionyl chloride | ||
With tetrachloromethane; triphenylphosphine Heating; | ||
With thionyl chloride In tetrahydrofuran at 20℃; for 5h; | ||
100 %Spectr. | With pyridine; thionyl chloride In dichloromethane | |
With thionyl chloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; Schlenk technique; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With chlorocarbonylbis(triphenylphosphine)iridium(I); hydrazine hydrate; potassium hydroxide In methanol at 160℃; for 3h; Sealed tube; | |
88% | With chlorocarbonylbis(triphenylphosphine)iridium(I); hydrazine hydrate; potassium hydroxide In methanol at 160℃; for 3h; Sealed tube; | |
86% | With manganese; (1,2-dimethoxyethane)dichloronickel(II); 1,1,3,3-Tetramethyldisiloxane; potassium <i>tert</i>-butylate; 1,3-bis(cyclohexyl)imidazolium tetrafluoroborate In toluene at 70℃; for 5h; |
81% | Stage #1: biphenyl-4-yl methanol With n-hexylmagnesium chloride; iron(II) bromide; tricyclohexylphosphine In tetrahydrofuran at 20℃; for 0.0833333h; Inert atmosphere; Stage #2: In di-isopropyl ether; toluene at 120℃; for 24h; Inert atmosphere; | |
With ethanol; palladium Hydrogenation; | ||
63 % Spectr. | With oxalic acid diethyl ester electrolysis; | |
With zinc In acetic acid | ||
Multi-step reaction with 2 steps 1: pyridine / diethyl ether / 12 h / Heating 2: electrolysis | ||
Multi-step reaction with 3 steps 1: 63 percent Spectr. / EtO2C.CO2Et / electrolysis 2: Bu4NBF4 / CH2Cl2 / electrolysis 3: electrolysis | ||
Multi-step reaction with 4 steps 1: pyridine / diethyl ether / 12 h / Heating 2: 19 percent Spectr. / electrolysis 3: pyridine / diethyl ether / 12 h / Heating 4: electrolysis | ||
Multi-step reaction with 4 steps 1: pyridine / diethyl ether / 12 h / Heating 2: 8 percent Spectr. / electrolysis 3: Bu4NBF4 / CH2Cl2 / electrolysis 4: electrolysis | ||
Multi-step reaction with 5 steps 1: pyridine / diethyl ether / 12 h / Heating 2: 19 percent Spectr. / electrolysis 3: 63 percent Spectr. / EtO2C.CO2Et / electrolysis 4: Bu4NBF4 / CH2Cl2 / electrolysis 5: electrolysis | ||
Multi-step reaction with 3 steps 1: pyridine / diethyl ether / 12 h / Heating 2: 19 percent Spectr. / electrolysis 3: 63 percent Spectr. / EtO2C.CO2Et / electrolysis | ||
Multi-step reaction with 2 steps 1: pyridine / diethyl ether / 12 h / Heating 2: 8 percent Spectr. / electrolysis | ||
Multi-step reaction with 2 steps 1: acetic acid; HBr 2: palladium; ethanol / Hydrogenation | ||
97 %Chromat. | With 2,4,6-trimethyl-pyridine; 4,4'-dimethoxyphenyl disulfide; iridium(lll) bis[2-(2,4-difluorophenyl)-5-methylpyridine-N,C20]-4,40-di-tert-butyl-2,20-bipyridine hexafluorophosphate; triphenylphosphine In toluene for 24h; Irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With carbon tetrabromide; triphenylphosphine; In dichloromethane; at 20℃; for 1.5h; | Carbon tetrabromide (8.99 g, 27.1 MMOL) and triphenyl phosphine (7.11 g, 27.1 MMOL) were added to a stirred solution of biphenyl-4-yl methanol (5.00 g, 27.1 MMOL) in dichloromethane (100 mL) at room temperature. Stirring was continued at room temperature for 1.5 hours then the solvent removed by evaporation under reduced pressure. The residue was purified by column chromatography on silica gel (1: 20 diethyl ether: cyclohexane) to give the title compound (6.37g, 95%) as a white solid.'H NMR (400 MHz: CDCI3) : 7.6 (4 H), 7.45 (4 H), 7.35 (1 H), 4.55 (2 H). |
95% | With carbon tetrabromide; triphenylphosphine; In dichloromethane; at 20℃; for 1.5h; | Carbon tetrabromide (8.99 g, 27.1 mmol) and triphenyl phosphine (7.11 g, 27.1 mmol) wereadded to a stirred solution of biphenyl-4-yl methanol (5.00 g, 27.1 mmol) indichloromethane (100 ml_) at room temperature. Stirring was continued at room temperaturefor 1.5 hours then the solvent removed by evaporation under reduced pressure. Theresidue was purified by column chromatography on silica gel (1:20 diethyl ether:cyclohexane) to give the title compound (6.37g, 95%) as a white solid. 1H NMR (400 MHz:CDCI3): 7.6 (4 H), 7.45 (4 H), 7.35 (1 H), 4.55 (2 H). |
91% | With phosphorus pentoxide; potassium bromide; In acetonitrile; at 20℃; for 1h; | General procedure: To a mixture of alcohol (1 mmol) and KBr (1.5 mmol, 0.18 g) in acetonitrile (5 mL), P2O5 (1.5 mmol, 0.23 g) was added and the reaction was stirred at room temperature for the time specified in Table 3. After reaction completion (TLC or GC), the reaction mixture was filtered and the residue washed with ethyl acetate (3 × 8 mL). The combined organic layers were washed with water (10 mL) and dried over Na2SO4. The solvent was removed under reduced pressure to afford the corresponding product. If necessary, further purification was performed by column chromatography. |
75% | With phosphorus tribromide; In chloroform; di-isopropyl ether; | Reference Example 50 4-Phenylbenzyl Bromide To a solution of 4-phenylbenzyl alcohol (1.00 g, 5.43 mmol) in a mixture of diisopropyl ether (10 mL) and chloroform (20 mL) was added phosphorus tribromide (0.98 g, 3.62 mmol) with ice-cooling and the mixture was stirred at room temperature for 1 hour. This reaction mixture was diluted with water and extracted with diisopropyl ether. The organic layer was washed with water and saturated aqueous sodium hydrogen carbonate solution, dried over MgSO4, and filtered. The filtrate was concentrated under reduced pressure and the residue was recrystallized from ethanol-hexane to provide 1.00 g of the title compound. Yield 75%. m.p. 86-88 C. 1H-NMR (CDCl3) delta: 4.55 (2H, s), 7.32-7.67 (9H, m). |
With carbon tetrabromide; triphenylphosphine; In dichloromethane; at 20℃; for 2h; | Carbon tetrabromide (8.99 g) and triphenylphosphine (7.11 g) were added to a stirred solution of biphenyl-4-yl-methanol (5.00 g) in dichloromethane (100 ml) at room temperature and stirrred the reaction mixture for approximately 2 hours at the same temperature. The solvent was evaporated under reduced pressure and the residue thus obtained was purified by column chromatography using 5% diethylether in hexane as eluant to furnish the title compound (6.37 g) . | |
With N-Bromosuccinimide; triphenylphosphine; In dichloromethane; | (A) 4-Phenylbenzyl Bromide Triphenylphosphine (1.58 g) and N-bromosuccinimide (1.07 g) were added to a stirred solution of 4-hydroxymethylbiphenyl (1.01 g) in dichloromethane (10 mL) under nitrogen. The mixture was stirred at room temperature for 15 hr and evaporated in vacuo. The residue was diluted with chloroform, and washed with saturated sodium hydrogencarobonate, and brine. The organic layer was dried over anhydrous sodium sulfate and evaporated in vacuo. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:100 to 1:50, v/v) to give the titled compound (1.26 g) as colorless crystals: 1H-NMR (400 MHz, CDCl3) delta 4.55 (s, 2H), 7.33-7.38 (m, 1H), 7.41-7.49 (m, 4H), and 7.54-7.60 (m, 4H). | |
With carbon tetrabromide; triphenylphosphine; In dichloromethane; at 20℃; for 2h; | Synthesis of 4-(bromomethyl)biphenylCarbon tetrabromide (8.99 g) and triphenylphosphine (7.11 g) were added to a stirred solution of biphenyl-4-yl-methanol (5.00 g) in dichloromethane (100 ml) at room temperature and stirrred the reaction mixture for approximately 2 hours at the same temperature. The solvent was evaporated under reduced pressure and the residue thus obtained was purified by column chromatography using 5% diethylether in hexane as eluant to furnish the title compound (6.37 g). | |
With phosphorus tribromide; lithium bromide; In DMF (N,N-dimethyl-formamide); at 20℃; for 1h; | Step 5.Preparation of 4-Bromomethyl-biphenyl (Compound 1E) biphenyl-4-yl-methanol (500 mg, 2.72 mmol) phosphorus tribromide (809 mg, 2.99 mmol), and lithium bromide (260 mg, 2.99 mmol) were dissolved in 10 ml DMF and stirred at ambient temperature for 1 h.water (10 ml) was added and the crude product was extracted into dichloromethane, dried over anhydrous sodium sulfate, filtered through silica gel, and concentrated. MS m/z 167 (M+1-Br). | |
627 mg | With phosphorus tribromide; In diethyl ether; at 20℃; for 1h;Cooling with ice; | In a 50 mL round bottom flask, c1 (368 mg, 2 mmol) was dissolved in 10 mLTo the anhydrous diethyl ether, phosphorus tribromide (0.21 mL, 2.2 mmol) was added under ice-cooling, and then the reaction system was transferred to room temperature for 1 hour, and the reaction was monitored by TLC. To the reaction system, slowly add water to quench the phosphorus tribromide, add 10 mL of dichloromethane, wash with water (2 × 10 mL), wash the organic layer with saturated brine, dry over anhydrous sodium sulfate, (Petroleum ether: ethyl acetate = 30:1) was purified to give a white powdery solid C 627mg.The total yield in two steps was 80%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | 105.1 (1) (1) 1,1'-Biphenyl-4-methylalcohol The object compound was obtained from 4-phenylbenzoic acid as an oily substance, according to the similar manner to that of Example 99 (1). yield: 100% 1H-NMR (CDCl3) δ; 1.22-1.89 (10H, m), 2.54 (1H, m), 4.65 (2H, s), 7.19 (2H, d, J=8.0 Hz), 7.29 (2H, d, J=8.0 Hz). IR (KBr) cm-1; 3270, 2926, 2851, 1449, 1001, 800. | |
99% | Stage #1: biphenyl-4-carboxylic acid With lithium aluminium hydride In tetrahydrofuran; diethyl ether at 20℃; for 4h; Cooling with ice; Inert atmosphere; Stage #2: With water monomer In tetrahydrofuran; diethyl ether for 16h; | |
89% | With lithium aluminium hydride In tetrahydrofuran at 20℃; for 2h; Inert atmosphere; |
With lithium aluminium hydride | ||
Multi-step reaction with 2 steps 1: HCl 2: LiAlH4 | ||
Multi-step reaction with 3 steps 1: thionyl chloride / 5 h / Reflux; Inert atmosphere 2: triethylamine / dichloromethane / 20 °C / Inert atmosphere 3: sodium 2-methyl-2-adamantoxide; sodium hydride; dichlorobis(dicyclohexylphosphinomethylpyridine)-ruthenium (II); hydrogen / toluene; mineral oil / 24 h / 160 °C / 45004.5 Torr / Inert atmosphere; Autoclave | ||
Multi-step reaction with 2 steps 1: sulfuric acid / Inert atmosphere; Glovebox; Reflux 2: lithium aluminium hydride / tetrahydrofuran / 20 °C / Inert atmosphere; Glovebox |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With tributylphosphine; 1,1'-azodicarbonyl-dipiperidine In benzene for 2h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | Stage #1: 4-Phenylbenzaldehyde With zinc diacetate In tetrahydrofuran at 65℃; for 0.166667h; Stage #2: With methyl-di(n-propoxy)silane In tetrahydrofuran at 65℃; for 24h; Stage #3: With hydrogenchloride; water at 0℃; for 1h; | |
99% | With iron(II) fluoro{tris[2-(diphenylphosphino)phenyl]phospino}tetrafluoroborate; hydrogen; trifluoroacetic acid In isopropyl alcohol at 120℃; for 2h; Inert atmosphere; Autoclave; chemoselective reaction; | |
99% | With C46H49CoN3P4(2+)*2BF4(1-); hydrogen; potassium hydroxide In ethanol; acetonitrile at 60℃; for 24h; Autoclave; Glovebox; chemoselective reaction; |
98% | With sodium tetrahydroborate In methanol at 20℃; for 1h; | |
98.3% | With sodium tetrahydroborate In ethanol for 5h; | |
96% | With sodium tetrahydroborate; sodium hydroxide In water at 55℃; for 1.5h; Green chemistry; | |
95% | With lithium hydride In tetrahydrofuran at 0 - 20℃; for 1h; Inert atmosphere; Schlenk technique; | |
95% | With sodium tetrahydroborate In methanol at 0 - 20℃; for 15.5h; | |
95% | With ammonium chloride; zinc In tetrahydrofuran; water at 20℃; for 0.333333h; | |
92% | With C9H8BrMnN2O3; potassium <i>tert</i>-butylate In isopropyl alcohol at 80℃; for 0.333333h; Inert atmosphere; Schlenk technique; Glovebox; | |
92% | Stage #1: 4-Phenylbenzaldehyde With 1,1,3,3-Tetramethyldisiloxane; [Mn(Si(SiMe3)3)2(tetrahydrofuran)2] at 80℃; for 6h; Stage #2: With tetrabutyl ammonium fluoride In water | |
91% | With Mn(CO)<SUB>3</SUB>Br(k<SUP>2</SUP>P,N-Ph<SUB>2</SUB>PN(H)Py); hydrogen; potassium hexamethylsilazane In toluene at 80℃; for 20h; Glovebox; Autoclave; Inert atmosphere; | |
90% | With C8H20N(1+)*C18H10F12O2P(1-); lithium chloride at 20℃; for 1h; | |
90% | Stage #1: 4-Phenylbenzaldehyde With tetrabutylammonium tricarbonylnitrosylferrate; tricyclohexylphosphine In 1,4-dioxane at 50℃; Inert atmosphere; Stage #2: With water; sodium hydroxide In 1,4-dioxane; methanol at 20℃; for 1.5h; Inert atmosphere; Stage #3: at 20℃; chemoselective reaction; | |
89% | With C8H20N(1+)*C18H10F12O2P(1-) In tetrahydrofuran for 1h; Inert atmosphere; | |
89% | With sodium tetrahydroborate In methanol at 0℃; Inert atmosphere; | [1,1’-Biphenyl]-4-methanol.(27a) General procedure: Aldehyde (1 mmol) was dissolved in 10 ml ofmethanol(ethanol for ketones) and cooled to 0oC. NaBH4 (3 mmol) was then added inone portion and the reaction was allowed to stir until completion as indicatedby TLC (9:1 heptanes/ethyl acetate). The reaction was quenched with 0.1 N NaOH(10 ml) and extracted three times with ethyl actetate. The organic layer waswashed with brine and dried over Na2SO4. The solvent wasremoved under reduced pressure and the resulting yellow oil was subjected toflash chromatography. |
89% | Stage #1: 4-Phenylbenzaldehyde With phenylsilane; C24H45BN2P2PtS In hexane at 65℃; for 3h; Inert atmosphere; Sealed tube; Stage #2: With sodium hydroxide In hexane; water at 20℃; for 2h; Inert atmosphere; Sealed tube; | |
88% | With CdS(x)Se(1-x) x:0-1;; cesium acetate; para-thiocresol In toluene Sealed tube; Inert atmosphere; Irradiation; | |
82% | With formic acid; water; palladium diacetate; tricyclohexylphosphine In 1,4-dioxane at 90℃; for 18h; Inert atmosphere; Sealed tube; chemoselective reaction; | Typical procedure and Spectral Data for Products General procedure: An oven-dried pressure tube containing a Teflon-coated stirring bar was charged with Pd(OAc)2 (11.2 mg, 5 mol%), PCy3 (21 mg, 7.5 mol%) and aldehyde(1 mmol).The tube was sealed, evacuated and backfilled with N2. 1 mL of dioxane was subsequently injected. After the mixture was stirred at room temperature for 15 min, H2O (180 mg, 10 equiv) and HCO2H (184 mg, 4 equiv) were injected and the reaction was heated to 90 oC for 18 h. After the reaction was completed, the solvent was removed under vacuo. The residues were purified by flash column chromatography on silica gel to afford 87 mg of benzyl alcohol in 81 % yield. |
80% | With [Re(NH{CH2CH2P(iPr2)}2)(CO)3]Br; potassium <i>tert</i>-butylate; hydrogen In toluene at 70℃; for 2h; Inert atmosphere; Glovebox; Autoclave; | |
78% | With methanol at 20℃; Neat (no solvent); | |
75% | With caesium carbonate In water; isopropyl alcohol at 120℃; for 4h; | 2.5. Procedure for selective reduction of benzaldehydes General procedure: The selective reduction of various benzaldehydes was carriedout by dissolving 2 mmol of the corresponding benzaldehyde ina similar ratio of H2Oand ipr-OH followed by the addition of 2equivalents of Cs2CO3 and 25 mg of CoCr2O4-HNT. The reactionmixture was then refluxed for 4 h at 120 °C and the progress ofthe reaction was monitored by TLC analysis and the resultantbenzyl alcohol was separated by column chromatography. |
72% | With rongalite In water; N,N-dimethyl-formamide at 100℃; for 5h; | |
69% | With formaldehyd; tricarbonyl(η4-1,3-bis(trimethylsilyl)-4,5,6,7-tetrahydro-2H-inden-2-one)iron; water; sodium carbonate In dimethyl sulfoxide at 120℃; for 24h; Inert atmosphere; Sealed tube; | Reduction of benzaldehyde to benzylalcohol General procedure: Knölker iron complex 2a (3 mol %,12.6 mg), paraformaldehyde (300 mg, 10 mmol), and Na2CO3 (106 mg, 1 mmol,1.0 equiv) and a stirring bar were charged in a pressure tube and flushed withargon. DMSO (1.0 mL), degassed water (1.0 mL), and benzaldehyde (1 mmol)were added under an argon atmosphere to the pressure tube with a syringe.The pressure tube was placed in oil and heated at 120 C for 24 h, then cooledto room temperature. The reaction mixture was neutralized with HCl (1M) andstirred for 30 min. After extraction with EtOAc for 3 times, the combinedorganic layers were dried over MgSO4. The crude product was purified bycolumn chromatography (Heptane/EtOAc: 70:30). The reaction was cooled toroom temperature and hexadecane (100 lL) was added as a GC internalstandard. |
54% | With methyl magnesium iodide In toluene at 80℃; Ionic liquid; Inert atmosphere; | |
43% | With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate; tris[3,5-bis(trifluoromethyl)phenyl]-borane In 1,4-dioxane at 25℃; for 12h; Glovebox; | General procedure for the hydrogenation reaction General procedure: In a glovebox, aldehydes (0.25 mmol) and the Hantzsch ester 1 (95 mg, 0.38 mmol) were added to asolution of tris[3,5-bis(trifluoromethy)phenyl]borane (9) (8.1 mg, 12.5 μmol) in 1 mL of anhydrous1,4-dioxane. The reaction mixture was stirred at 25 or 100 C for 12 h. An internal standard (biphenylor mesitylene) was added to the reaction mixture and filtrated through a cotton plug. The resultingsolution was analyzed with gas chromatography. |
With silica gel; sodium hydrogensulfite; diborane multistep reaction, competition reaction with 4-phenylacetophenone; selectivity of reduction; other substrates; | ||
With isopropyl alcohol at 160℃; | ||
With lithium aluminium tetrahydride; sodium hydrogensulfite 1) aq. EtOH; Yield given. Multistep reaction; | ||
With pyridine; 1-methyl-pyrrolidin-2-one; H2SiEt2; Trimethylmethoxysilane; RhCl(PPh3)3; polystryrene-diethylsilane; hydrogen fluoride solid phase synthesis; 1) 2 h, 60 deg C; Yield given. Multistep reaction; | ||
With hydrogen; magnesium In methanol at 20℃; for 0.25h; | ||
Stage #1: 4-Phenylbenzaldehyde With [CpFe(IMes)(CO)I]; phenylsilane In toluene at 30℃; for 3h; Inert atmosphere; Stage #2: With methanol; sodium hydroxide In water; toluene at 20℃; for 1h; Inert atmosphere; | ||
With methanol; sodium tetrahydroborate at 0℃; for 0.5h; | ||
With sodium tetrahydroborate | ||
99 %Chromat. | With formic acid; iron(II) tetrafluoroborate hexahydrate; tris(2-diphenylphosphinoethyl)phosphine In tetrahydrofuran at 60℃; for 2h; Schlenk technique; Inert atmosphere; | 2. Experimental General procedure: Fe(BF4)2·6H2O (0.7 mg; 0.002 mmol) and tris[2-(diphenyl-phosphino)-ethyl]phosphine [P(CH2CH2PPh2)3; tetraphos] (1.4 mg; 0.002 mmol) are placed in a Schlenk-tube under argon atmosphere. 1 mL dry tetrahydrofurane is added and the purple solution is stirred for 2 min. Cinnamaldehyde (63 μL; 0.5 mmol) and 100 μL n-hexadecane as an internal GC-standard are injected and a sample is taken for GC-analysis. The solution is heated to 60 °C and the reaction starts by addition of 1.1 equiv formic acid (22 μL; 0.55 mmol). After 2 h, a second sample is taken for GC-analysis and conversion and yield are determined by comparison with authentic samples. For the isolation, the reaction is scaled up by a factor of 20. When the reaction is completed, the reaction solution is diluted with a mixture of n-hexane and ethyl acetate (3:1), filtered through a plug of silica and the solvent removed in vacuum. |
With sodium tetrahydroborate; water In acetonitrile | ||
With sodium tetrahydroborate Inert atmosphere; | ||
88 %Spectr. | With 2,2'-bi(1,3,6,2-dioxazaborocane); water at 20℃; for 18h; Inert atmosphere; Sealed tube; | |
With methanol; sodium tetrahydroborate at 0 - 20℃; for 3h; Inert atmosphere; | ||
89 %Chromat. | With C28H35ClCoN5(1+)*Cl(1-); potassium <i>tert</i>-butylate; hydrogen In tetrahydrofuran at 60℃; for 16h; Autoclave; | General procedure for Hydrogenation of Ketones General procedure: In an argon filled glove box, the cobalt catalyst (LNHC/CoCl2 or Co-2a) and the base wereweighted into a 4mL vial equipped with a magnetic stir bar, followed by addition of the solvent.After shaking of the vial for 30 seconds, the carbonyl substrate was then added. The vial wasplaced into a Parr Instruments autoclave, which was then sealed, removed from the glove boxand purged with hydrogen gas. The autoclave was heated to certain temperature. After reactionfor 16 hours, the autoclave was cooled down to 0 oC before releasing the hydrogen gas. Forquantitative GC analysis, biphenyl (1.0 mmol) as internal standard was added. The organiclayer was then filtrated and diluted for GC analysis. The stereo-selectivity of the hydrogenatedproducts of cyclohexanones were determined by NMR with mesitylene as the internal standard.The desired hydrogenation product was further isolated by flash column chromatography. |
With sodium tetrahydroborate In methanol at 20℃; for 0.75h; Cooling with ice; | 3.1 First step: Preparation of 4-biphenylbenzyl alcohol (c1) In a 50 mL round bottom flask,4-Bibenzaldehyde (365 mg, 2 mmol) was dissolved in 10 mL of methanol.Sodium borohydride (151 mg, 4 mmol) was added portionwise under ice bath.Then the reaction system was transferred to room temperature for 45 minutes.TLC monitored the reaction completely.After the solvent is removed from the reaction system,After adding 10 mL of dichloromethane, it was washed with water (2×10 mL), and the organic layer was washed with brine.Filtered and concentrated to obtain a yellow powdery crude c1.Can be used to directly invest in the next step. | |
With methanol; sodium tetrahydroborate at 0℃; | ||
Multi-step reaction with 2 steps 1: C84H108Cl2N10Pd2 / neat (no solvent) / 12 h / 60 °C / Glovebox 2: silica gel; methanol / 6 h / 60 °C | ||
> 99 %Spectr. | With water; benzo[1,3,2]dioxaborole In N,N-dimethyl acetamide at 80℃; for 12h; Inert atmosphere; Sealed tube; | |
With sodium tetrahydroborate In methanol at 20℃; for 0.5h; | 4.2.19. [1,1'-biphenyl]-4-ylmethanol (5) [45] This compound was obtained after the treatment of the crude reaction mixture with NaBH4 (37.8 mg, 5.0 equiv) in MeOH at rt for 30 min, which was followed by the same purification process as that of aldehyde 3a (Table 2). A white solid; 1H NMR (500 MHz, CDCl3) δ 7.61-7.57 (m, 4H), 7.46-7.42 (m, 4H), 7.35 (t, J = 7.5 Hz, 1H), 4.74 (s, 2H), 1.79 (br s, 1H) ppm; 13C NMR (125 MHz, CDCl3) δ 140.8, 140.6, 139.8, 128.8, 127.4, 127.3, 127.1, 65.1 ppm (one carbon signal is missing) | |
With sodium tetrahydroborate In methanol at 0 - 20℃; for 1h; Inert atmosphere; | ||
With methanol; sodium tetrahydroborate at 0℃; Schlenk technique; Cooling with ice; Inert atmosphere; | ||
With sodium tetrahydroborate In methanol at 0 - 20℃; for 3h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With potassium <i>tert</i>-butylate In dimethyl sulfoxide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | Stage #1: biphenyl-4-yl methanol With sodium hydride In N,N-dimethyl-formamide at 30℃; for 1h; Stage #2: sodium 2-bromoacetate In N,N-dimethyl-formamide for 12h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With n-butyltriphenylphosphonium permanganate In acetonitrile at 20℃; for 0.25h; | |
99.7% | With silica-supported Jones reagent In dichloromethane for 0.00269444h; | |
99% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; N-methyl-N-[3-(4'-diacetoxyiodo)phenoxy-1-propyl]pyrrolidinium 4-methylbenzenesulfonate In dichloromethane at 20℃; for 6h; |
99% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; N-methyl-N-[3-(4-diacetoxyiodo)phenoxy-1-propyl]pyrrolidinium 4-methylbenzenesulfonate In dichloromethane at 20℃; for 6h; Inert atmosphere; | |
99% | With dihydrogen peroxide In water at 80℃; for 6h; Green chemistry; | |
99% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; iodic acid In N,N-dimethyl-formamide at 20℃; for 2h; Inert atmosphere; | 4.1.14 4.1.2 Typical experimental procedure with HIO3 in the presence of TEMPO (Method B) General procedure: To a solution of 1-(p-bromophenyl)ethanol I-23 (201 mg, 1.0 mmol) in DMF (2.0 mL) was added HIO3 (194 mg, 1.1 mmol) and TEMPO (7.8 mg, 0.05 mmol). The mixture was stirred for 2 h at room temperature under an Ar atmosphere. After the reaction, the reaction mixture was poured into aq Na2S2O3, and extracted with a mixture of Et2O: hexane=1:1 (3*10 mL). Then, the organic layer was poured into satd NaCl (10 mL) and extracted with Et2O (10 mL). The organic layer was dried over Na2SO4. After being filtration and removal of the solvent under reduced pressure, the residue was purified by flash short column chromatography on silica gel (EtOAc-hexane, 1:4) to give p-bromoacetophenone II-23 in 99% yield. |
99% | With 1-methyl-1H-imidazole; [2,2]bipyridinyl; copper(l) iodide; 1,3-diphenyltetrazolium-5-hydroxyamide; oxygen In acetonitrile at 20℃; for 3h; chemoselective reaction; | General Procedure for the Optimization of the Cu-1-CatalyzedAerobic Oxidation of Benzyl Alcohol (Table 1): General procedure: Amixture of benzyl alcohol 2a (0.4 mmol), Cu salt (0.02 mmol)ligand (0.02 mmol), base (0.04 mmol), and 1 (0.02 mmol) wasvigorously stirred in MeCN (4.0 mL) at room temperature for 24h in the presence of PhCN (0.2 mmol) as an internal standard. Atintervals, aliquots were analyzed by GC after being passedthrough a SiO2 column eluted with CH2Cl2. The yield of benzaldehyde3a (tR = 4.3 min) and the recovery of 2a (tR = 9.4 min)were calculated on the basis of calibration curves by usingauthentic samples |
99% | With fluorosulfonyl fluoride; potassium carbonate; dimethyl sulfoxide at 20℃; for 16h; Sealed tube; chemoselective reaction; | |
98% | With sodium hypochlorite solution; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; isocyanuric acid In ethyl acetate at 0 - 10℃; for 1h; | General Procedure for the oxidation of alcohols employing nitroxyl radical / imide / NaOCl without K2CO3. General procedure: To a mixture of the alcohol (7.679 mmol), and cyanuric acid (0.1 equiv, 0.384 mmol) in 40 mL of ethyl acetate was added TEMPO or AZADO (3 mol%, 0.230 mmol) at 0-10°C. 12% NaOCl (1.2 equiv, 9.215 mmol, Wako Pure Chemical Industries, Ltd.) was added dropwise with keeping >pH 7 at 0-10°C. The mixture was then stirred for 1 hour. The reaction mixture was extracted with ethyl acetate. The organic layer was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography to afford the corresponding product. |
98% | With 1-methyl-1H-imidazole; [2,2]bipyridinyl; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; tetrakis(acetonitrile)copper(I) trifluoromethanesulfonate; sodium chloride In neat (no solvent) Milling; Green chemistry; | General procedure to prepare carbonyl compounds 2a-v. General procedure: 2,2,6,6-Tetramethylpiperidine 1-oxyl (TEMPO, 9.4 mg,0.06 mmol, 3 mol %), 2,2′-bipyridyl (9,4 mg, 0.06 mmol,3 mol %), [Cu(CN)4]OTf (22.6 mg, 0.06 mmol, 3 mol %) and1-methylimidazole (NMI, 11.5 mg, 11.2 μL, 0.14 mmol,7 mol %) were placed in a zirconia-milling beaker (45 mL)equipped with four balls (two balls × 5 mm , two balls ×12 mm ) of the same material. The jar was sealed and ballmilled for 1 min. Then, benzyl alcohol (216.3 mg, 207 μL,2.0 mmol), NaCl (1.0 g) together with other two zirconia balls(12 mm ) were added and the reaction mixture was subjectedto grinding for further 10 minutes overall (two cycles of5 minutes each). The first milling cycle was followed by a breakof 2 min leaving in the meantime the uncovered jar in open air.The progress of the reaction was monitored by TLC analysis(heptane/AcOEt 9:1 v/v) and GC-MS analysis on an aliquot ofthe crude. Upon completion of the ball milling process, the jarwas opened, the milling balls were removed and the resultingcrude product (adsorbed on NaCl) was then easily transferredinto a separating funnel filled with an aqueous 10% citric acidsolution (20 mL). The aqueous phase was extracted withcyclopentyl methyl ether (or alternatively with AcOEt)(3 × 15 mL). The combined organic fractions were washed withH2O (25 mL) and brine (25 mL), then dried over Na2SO4, andconcentrated in vacuo to give benzaldehyde in high yield (195 mg, 92%) and good purity (>93% by GC analysis). Alternatively, after completion of the reaction, the resulting crudeproduct (adsorbed on NaCl) can be also easily purified by ashort column chromatography on silica gel using heptane/ethylacetate (9:1 v/v) as the eluents to afford pure aldehyde 2b inhigh yield (202 mg, 95%) as a colourless liquid. |
97% | With 2C36H60N9(3+)*3O4W(2-); dihydrogen peroxide In water at 20℃; for 0.133333h; Green chemistry; | |
97% | With 1,1,1,3',3',3'-hexafluoro-propanol; 5-trimethylammonio-1,3-dioxo-1,3-dihydro-1λ5-benzo[d][1,2]-iodoxol-1-ol anion; trifluoroacetic acid at 20℃; for 0.3h; | |
96% | With magnesium sulfate; pyridinium chlorochromate In chloroform for 3h; Sealed tube; | General synthesis for biphenyl-4-carbaldehyde Anoven dried 100 mL round bottom was charged with 2.00 g (10.85 mmol) of biphenyl-4-yl-methanol, 30 mlof chloroform, 10.5g of anhydrous magnesiumsulfate and a magnetic stir bar.The solution was then allowed to stir until the solution was homogenous, 4.5 g of pyridinium chlorochromate was then added and the vessel was sealed and allowed to react for 3 hours. Reaction progress was checked by TLC andonce the reaction was complete excess solvent was removed via rotovap. Thes olution was then purified via a silica column. The purification yielded a yellow oil that was thenre-crystallized into a white crystalline solid with hexane and dichloromethane.(1.90 g, 10.43 mmol, 96%) |
95% | With tris(bipyridine)ruthenium(II) dichloride hexahydrate; 1-(benzyloxy)-1λ3-benzo[d][1,2]iodaoxol-3(1H)-one In 2,2,2-trifluoroethanol at 40℃; for 3h; UV-irradiation; | |
94% | With dihydrogen peroxide; bromine In water; ethyl acetate for 4h; Reflux; | |
94% | With potassium bromide In dichloromethane at 0℃; for 0.166667h; | |
94% | With sodium hypochlorite; sodium bromide In dichloromethane; water at 0℃; for 1h; | General procedure of the selective oxidation of alcohols General procedure: Alcohol (0.8 mmol), NaBr (1.25 mol%), and TEMPO-P(MEO2MA-co-OEGMA) (109 mg, 0.008 mmol) were added to the mixed solution of NaClO (1.0 mmol, 1.25 mol equil., 2 mL) and CH2Cl2 (2 mL) at 0 °C. The resulting mixture was vigorously stirred at 0 °C. After the reaction was completed, ether was added to extract CH2Cl2, unreacted alcohol and product. The conversion was analyzed by GC-MS. The catalyst was left in aqueous phase and recovered by heating/centrifugation, which was used for next run after thoroughly washing with cold ether. |
93% | With dipotassium peroxodisulfate; sodium chloride In acetonitrile for 0.833333h; Reflux; Green chemistry; chemoselective reaction; | |
93% | With tetrabutylammomium bromide; triethylamine In decane; toluene at 110℃; for 24h; | |
92% | With Iron(III) nitrate nonahydrate; oxygen; 2,3-dicyano-5,6-dichloro-p-benzoquinone In 1,2-dichloro-ethane at 60℃; for 3h; Schlenk technique; Green chemistry; | |
92% | With dimanganese decacarbonyl In toluene at 120℃; for 12h; Sealed tube; | |
92% | With dihydrogen peroxide In water; acetonitrile at 70℃; for 10h; Green chemistry; | General procedure for selective oxidation of alcohols using cu-nhcpyrmomsmaterials General procedure: To a 25 mL round bottomed flask equipped with a condenser andmagnetic stir bar was added alcohol (10 mmol), 30% H2O2 (12 mmol,0.37 mL) in CH3CN/ H2O (2/1, 6 mL). Then, Cu-NHCPyrm-OMS(0.5mol%, 0.2 gr) was added to the above solution and the re-sultingmixture was stirred at 70 C for requisite time. The progress of the reactionwas monitored by TLC. After completion of the reaction, themixture was allowed to cool down to the room temperature and thecatalyst was filtrated and washed with ethyl acetate (10 ml) and driedfor next run. The filtrate was concentrated and extracted with mixture ofwater and ethyl acetate. Organic phase was separated, dried overmagnesium sulfate, filtrated through a pad of silica gel, and concentratedwith evaporation under the vacuum to give the correspondingcarbonyl compounds. |
91% | With Cp*Ir(6,6'-dionato-2,2'-bipyridine)(H2O) In <i>tert</i>-butyl alcohol at 130℃; for 20h; | |
91% | With 5-nitro-3-oxo-1λ3-benzo[d][1,2]iodaoxol-1(3H)-yl acetate In N,N-dimethyl-formamide at 65℃; for 24h; | |
91% | With iron(III) chloride hexahydrate; C17H26N3(1+)*Br(1-); dihydrogen peroxide In water at 20℃; for 2h; chemoselective reaction; | |
91% | With di-tert-butyl peroxide In N,N-dimethyl-formamide at 100℃; for 4.5h; | |
90% | With dinitrogen tetroxide impregnated on activated charcoal In dichloromethane at 20℃; for 5h; | |
90.3% | With sodium hypochlorite In 1,2-dimethoxyethane; water at 20 - 30℃; for 4h; | |
90% | With tungstate anion confined in hydrophilic/hydrophobic nanomaterials functionalized bronsted acidic imidazolium-based ionic liquid; air In water at 90℃; for 12h; | General procedure for selective aerobic oxidation of alcohols using PMO-IL-WO42- materials General procedure: A 25 mL single-necked round bottomed flask equipped with a condenser was charged with alcohol (10 mmol) and water (5 mL) were added and stirred. PMO -IL-WO42- (0.01 g) was then added to the above solution and the resulting mixture was stirred at 90 °C under atmospheric air pressure for the required time. The progress of the reaction was monitored by TLC and/or gas chromatography using standard addition method. After completion of the reaction, the mixture was allowed to cool down to room temperature and the catalyst was successfully filtrated, washed with ethyl acetate (2 x 10 mL) and dried under vacuum for the next run. Then, the filtrate was first washed with water, dried over magnesium sulfate, and the solvent concentrated with evaporation under vacuum to give the corresponding carbonyl compounds. |
89% | With tris(2-methoxyphenyl)bismuth oxide In dichloromethane at 20℃; for 0.166667h; | |
89% | With oxygen; iron oxide In methanol at 20℃; for 0.5h; Irradiation; | 2.5. Procedure for photocatalytic oxidation of benzyl alcohols General procedure: The photocatalytic oxidation of benzyl alcohols (BA) to benzaldehydeswith high selectivity in presence of the synthesized Fe2O3-HNTcatalyst was carried out in a photochemical reactor comprising of a 500mL of reaction chamber made up of quartz, surrounded by a 300 WXenon arc lamp along with a UV cut-off filter ( ≥ 420 nm) as the visiblelight source. The light source was encircled by a double-jacketed quartzimmersion by means of a well with an inlet and outlet for water circulationto ensure a safe temperature throughout the photocatalytic process.At first, 25 mg of the catalyst sample was immersed into 20 mL ofmethanol (MeOH) along with 2 mmol of BA in the photocatalytic reactionchamber. The reaction was performed with molecular oxygen(O2) as oxidant and the O2 was passed with a flow rate of 60 mL/min inpresence of light for 30 min. It was done by continual stirring by amagnetic stir placed inside the reactor. The whole photochemical reactionwas completed at RT. The reaction progress was monitoredthrough thin layer chromatography (TLC) using ethyl acetate/n-hexane,1:9. The resultant product i.e., benzaldehyde was separated by utilizingcolumn chromatographic analysis (100-200 mesh silica) with a mixtureof n-hexane and ethyl acetate as eluent. In the same way, the oxidant O2was replaced by 3 mmol of hydrogen peroxide (H2O2), and the reactionwas carried out by adding 2 mmol of BA into 20 mL of acetonitrile(CH3CN) followed by the addition of 25 mg of Fe2O3-HNT at RT. The photoirradiation time was set as 20 min. After 20 min the reaction wasquenched, and benzaldehyde was separated by chromatographic |
87% | With oxygen; potassium carbonate In toluene at 80℃; for 24h; | Aerobic oxidation of benzyl alcohols A mixture of K2CO3 (1 mmol) and the catalyst (52 mg, ∼3 mol% of Pd2+) in toluene (5 ml) was prepared in a two necked flask. The flask was evacuated and refilled with pure oxygen. To this solution, the alcohol (1 mmol, in 1 ml toluene) was injected and the resulting mixture was stirred at 80 °C under an oxygen atmosphere. After completion of reaction, the reaction mixture was filtered off and the catalyst rinsed twice with CH2Cl2 (5 ml). The excess of solvent was removed under reduced pressure to give the corresponding carbonyl compounds. |
87.4% | With titanium oxide alkene - sulfuric acid complex In tetrahydrofuran; water at 70℃; for 10h; | 16 Embodiment 16 The 1.25 g (0.0068 µM) of 4 - biphenyl methanol and GO - Ti compound 0.4 g dispersed in 10 ml in tetrahydrofuran and in the oil bath heated to 70 °C, 2.5 equivalent () of 30 wt % aqueous hydrogen peroxide solution in tetrahydrofuran is slowly added. After adding after keeping the temperature reaction 10 h, by HPLC detection 4 - biphenyl methanol conversion rate of 90.6%, 4 - biphenyl formaldehyde selectivity of 98.2%. The concentrated filtrate after filtering to remove the catalyst, after separation by silica gel column chromatography to obtain 4 - biphenyl formaldehyde 1.08 g, yield 87.4% |
87% | With Quinuclidine; 2,4,5,6‐tetra‐9H‐carbazol‐9‐yl‐1,3‐benzenedicarbonitrile; tetrabutylammonium dihydrogen phosphate In dimethyl sulfoxide; acetonitrile at 20℃; for 10h; Molecular sieve; Irradiation; Sealed tube; Green chemistry; | 3. General procedure for oxidation of benzylic primary and secondary alcohols General procedure: In a dry tube containing 4CzlPN (4.7 mg, 3mol%), quinuclidine (2.2mg, 10mol%), Bu4NH2PO4 (17mg, 25 mol%), MS (200 mg) in MeCN (1 ml) and DMSO (0.1 mL), benzyl primary and secondary alcohols (0.20 mmol) was added. The tube was sealed with an air balloon, and was left stirring under blue LEDs irradiation for 10 h. The desired product was isolated after purification by column chromatography. |
86% | With dihydrogen peroxide In water at 80℃; | 2.4 Reaction Conditions General procedure: In a typical process, benzyl alcohol (1 mmol), Cat.(0.5 mmol), 30 % aq H2O2 (2 mmol) were mixed and H2O(5 mL) was then added. The reaction mixture was refluxedat 80-85 °C for 28 h. The progress of the reaction wasmonitored by the TLC with samples taken periodically.After the completion of the reaction, the system cooledto room temperature. The catalyst was filtered and the filtrateextracted three times with Et2O. The organic layerwas dried over anhydrous MgSO4 and evaporated underreduced pressure. The product was purified by columnchromatograph to give benzaldehyde (98 % yield). The nextrun was performed under identical reaction conditions. Theproducts were recognized by comparing experimental datawith authentic samples. |
86% | With magnetic polydopamine-wrapped Fe3O4 core-shell submicrosphere-supported nano-palladium; air In o-xylene at 120℃; for 24h; Sonication; | The general procedure for the oxidative dehydrogenation of benzyl alcohol was as follows General procedure: Approximately 0.1 g of Fe3O4(at)PDAPd catalyst (2 mol% of Pd) was used. The aforementioned solidand liquor were separated using a magnet and placed under ultrasonic washing using 10 mL 3O-xylene. Then, 1 mmol of benzyl alcohol derivative and 5 mL of O-xylene were successively added and blended under ultrasonic conditions. The mixture was then magnetically stirred for 24 h under 120 °C. After the reaction ended, the solid and liquor were separated using a magnet. The liquor wasconcentrated, and the dehydrogenation product could be obtained after purification through column chromatography (petroleum ether/ethyl acetate). |
86% | With oxygen; nitric acid; 2,3-dicyano-5,6-dichloro-p-benzoquinone In dichloromethane; water at 20℃; for 18h; Sealed tube; | |
85% | With [Cp*Ir(6,6'-dihydroxy-2,2'-bipyridine)(H2O)](OTf)2 In water for 20h; Inert atmosphere; Reflux; | |
85% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; cesium hydroxide; [(2-(sulfonylquinlium-8-yloxy)phthalic acid-2H)2Cu4(4,4′-bipyridine)4]·2H2O}n·2nH2O In acetonitrile at 80℃; for 12h; | |
85% | With sym-collidinium chlorochromate; periodic acid In acetonitrile at 20℃; for 0.0833333h; | Typical procedure for the oxidation alcohols to aldehydes and ketones using periodic acid catalyzed by S-COCC General procedure: A solution of acetonitril (10 mL, 1mmol) and periodic acid was placed in flask and stir for the 15 min. Then, a mixture of alcohols (1mmol) and S-COCC (1%mmol) was added and the resulting mixture was stirred at room temperature for a suitable period (Table 3) and completion of the reaction investigated byTLC (n-hexane/EtOAc; 2:1) analysis. Then, EtOAc (20ml) was subjoined to the reaction mixture and after being washed with water/sodium solfite (1:1), the mixture was filtered off. The solvent was vaporized and produced pure products. |
80% | With C16H13ClIrNO(1-); sodium methylate In toluene for 20h; Reflux; Inert atmosphere; | |
80% | In acetonitrile at 25℃; for 15h; Schlenk technique; Inert atmosphere; Sealed tube; Irradiation; | |
79% | With m-iodosylbenzoic acid In water; acetonitrile at 20℃; for 2.5h; | |
77% | With silica supported nickel peroxide for 0.116667h; neat (no solvent); | |
77% | With 9-fluorenone In dimethyl sulfoxide at 20℃; Irradiation; | |
76% | With phosphotungstate-Fe3+ dual-metal-site modulated graphitic carbon nitride In acetonitrile at 25 - 35℃; for 15h; Sealed tube; Irradiation; | |
75% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In n-heptane at 80℃; for 24h; | Synthesis of Aldehydes 2a-y; General Procedure General procedure: A mixture of catalyst PS-PEG-TD2-Cu(OAc)2 (100 mg, 0.05mmol Cu), BnOH (1a, 27.0 mg, 0.25 mmol), and TEMPO (7.8 mg,0.05 mmol) in heptane (2.0 mL) was stirred at 80 °C for 24 hunder air (1 atm). The mixture was then cooled and filtered, andthe resulting solid material was washed with Et2O (3 × 2 mL).The organic phases were combined, concentrated to a volume of2 mL, and the internal standard was added to determine the GCyield. The crude product was purified by column chromatography[silica gel, hexane-Et2O (99:1)]. In the formation of somebenzaldehydes, low isolated yields were observed because ofinstability of the benzaldehydes on silica gel |
72% | With ethyl 2-bromoisobutyrate; dimethyl sulfoxide at 130℃; for 2.58333h; | 2. General procedure for oxidation of alcohols: General procedure: To a mixture of compound 1 (0.5 mmol, 1 equiv) and MMT K10 (0.5 mmol, 1 equiv141.1 mg) in DMSO (0.2 mL) was added ethyl bromoisobutyrate 2a (2.5 mmol, 5 equiv,367 μL). The resulting reaction mixture was stirred at 130 oC without exclusion of airuntil complete consumption of compound 1 (monitored by TLC). Then the reactionmixture was cooled to rt, diluted with DCM, and purified directly by a silica gel flashchromatography (Hexane/EtOAc) to give compound 3. |
70% | With cobalt chromium oxide supported on halloysite nanotubes catalyst In acetonitrile at 20℃; for 0.833333h; Irradiation; | 2.7. Procedure for photocatalytic oxidation of benzyl alcohols General procedure: The selective photochemical oxidation of benzyl alcohols (BA)to benzaldehydes in presence of the synthesized CoCr2O4-HNTcatalyst was carried out in a photochemical reactor having a500 mL of reaction chamber made up of quartz, encircled with450 W mercury lamp as the light source. Typically, 20 mg of thecatalyst sample was immersed into 20 mL of acetonitrile (CH3CN)along with 2 mmol of BA in the reaction chamber. Afterward, thereaction mixture was irradiated with the mercury lamp along withcontinuous stirring by a magnetic stir. The desired benzaldehydesproducts were separated by column chromatographic analysiswith hexane and ethyl acetate. The above photochemical reactionwas carried out at room temperature. The % conversion andselectivity of benzaldehyde formation were calculated fromGC-analysis. |
68% | With potassium phosphate; carbon dioxide In dimethyl sulfoxide at 90℃; for 48h; | |
66% | With oxygen In acetonitrile at 25℃; for 3.25h; UV-irradiation; | |
66% | With oxygen In acetonitrile at 20℃; for 1.5h; Irradiation; Green chemistry; chemoselective reaction; | Catalytic studies General procedure: In a Pyrex flask equipped with a magnet bar, a solution of the alcohol (5 mmol) in acetonitrile (10 mL) was prepared. To this solution PTA/Si-imid Si-MNPs (50 mg) was added and purged with O2 and joined through an inlet tube to a balloon filled with O2 before irradiation.The suspension was vigorously stirred and irradiated with a high pressure 400 W mercury lamp using a cut-off Pyrex filter at room temperature. The progress of the reaction was monitored by TLC. At the end of the reaction the organic layer was simply decanted by means of an external magnet. The decanted solution was purified on a silica-gel plate or a silica-gel column to obtain the pure product. The identities of the products were confirmed by FT-IR and 1H NMR spectral data. |
65% | With dihydrogen peroxide In acetonitrile at 70℃; for 2h; chemoselective reaction; | Catalytic Studies General procedure: In a typical run, a 25 mL flask was charged with catalyst (100 mg), acetonitrile (5 mL), alcohol (1 mmol), and H2O2 (3 mmol). This mixture was heated in an oil bath at 70°C and the progress of the reaction was monitored by TLC. At the end of the reaction, the catalyst was simply collected using a magnetic bar and the reaction mixture was then transferred out of the flask. The decanted solution was purified on a silica-gel plate or a silica-gel column to obtain the pure product. The structures of the products were established on the basis of their spectral analysis (IR, 1H NMR). |
65% | With dihydrogen peroxide In neat (no solvent) at 50℃; for 5h; Green chemistry; | 2.3. Catalytic studies General procedure: In a typical run, a 25 mL round-bottom flask equipped with a condenser and magnetic stirrer, was charged with: MN(at)[NH2-Cu(phen) 2 ] (0.04 g), benzylic alcohol (1 mmol), and H2O2 (6 mmol). This suspension was heated in an oil bath at 50 °C and the reaction was followed by GC. At the end of the reaction, the reaction mixture was simply decanted by means of an external magnet and was purified by silica-gel plate or a silica-gel column to obtain the pure product. The identities of the products were confirmed by FT-IR and 1H NMR spectral data. |
63% | With dimethyl sulfoxide UV-irradiation; | |
62% | With mercury(II) oxide In acetonitrile at 25℃; UV-irradiation; | |
60% | With manganese(IV) oxide; manganese(II) nitrate tetrahydrate; dibenzoyl peroxide In hexane at 70℃; for 0.333333h; chemoselective reaction; | |
52% | With oxygen In acetonitrile at 20℃; for 4.5h; UV-irradiation; | |
50% | With indium isopropoxide; pivalaldehyde In chloroform at 20℃; for 3h; Glovebox; Sealed tube; Inert atmosphere; | Oppenauer Oxidation of Alcohols Using In(i-OPr)3; General Procedure General procedure: To a screw tube in a glovebox was added In(Oi-Pr)3 (29.2 mg, 0.1 mmol). The tube was then sealed and removed from the glovebox, and CHCl3 (1 mL), alcohol (0.5 mmol), and pivalaldehyde (280 μL, 2.5 mmol) were added under N2 in this order. After stirring the mixture at r.t. for 3 h, H2O (1.0 mL) was added to the reaction mixture, which was then extracted with EtOAc. The organic phase was dried (Na2SO4), and evaporated under reduced pressure. The crude material was purified by silica gel column chromatography (Table 2 and Scheme 2). |
45% | With iodine; oxygen In acetonitrile at 20℃; for 6h; Irradiation; | |
43% | With Bromotrichloromethane; (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(2-phenylpyridine(-1H))-iridium(III) hexafluorophosphate In acetonitrile at 20℃; for 24h; Schlenk technique; Irradiation; Inert atmosphere; | General Procedure for synthesis of product General procedure: An 25 mL oven-dried Schlenk tube was equipped with a stirring bar, alcohols 1 (0.5 mmol) and Ir(ppy)2(dtbbpy)PF6 (0.005 mmol, 1 mol%). The mixture was degassed by using standard Schlenk techniques with an oil pump. Then MeCN (4 mL) and bromotrichloromethane (0.75 mmol, 1.5 eq) were injected into the reaction tube. The reaction mixture was placed under a 7 W blue LED and stirred at room temperature. After 24 h, the mixture was concentrated under reduced pressure using a rotary evaporator and the purification was done by column chromatography on silica gel (200-300 mesh) with petroleum ether / ethyl acetate as the eluent to give the pure product |
With manganese(IV) oxide In tetrahydrofuran at 20℃; for 4h; | ||
Multi-step reaction with 2 steps 1: 92 percent / CAN; 1-n-butylpyridinium chloroferrate / 0.67 h / 20 °C 2: 89 percent / 1-n-butylpyridinium chloroferrate; pyridinium chlorochromate / 0.5 h / 50 °C | ||
Multi-step reaction with 2 steps 1: 90 percent / CAN; 1-n-butylpyridinium chloroferrate / 0.6 h / 20 °C 2: 88 percent / 1-n-butylpyridinium chloroferrate; pyridinium chlorochromate / 0.33 h / 50 °C | ||
With triethylamine; trifluoroacetic acid In dichloromethane; dimethyl sulfoxide | 108 Synthesis of bromo-(4-biphenyl)-phenylmethane Synthesis of bromo-(4-biphenyl)-phenylmethane To a solution of dimethylsulfoxide (3.9 ml, 54.4 mmol) in methylene chloride (70 ml) under nitrogen atmosphere is added trifluoroacetic acid (5.7 ml, 40.8 mmol) with stirring at -70° C. After 10 min., 4-biphenylmethanol (5 g, 27.2 mmol) is added, and after being stirred for 30 min., triethylamine (30 ml, 218 mmol) is added. The reaction mixture is allowed to warm up to r.t., diluted with water, and extracted with methylene chloride. The organic layer is washed successively with 1N hydrochloric acid and saturated sodium bicarbonate, dried over magnesium sulfate and concentrated to give 4-biphenylmethanal. | |
94 %Chromat. | With oxygen; nitric acid In 1,4-dioxane; water at 90℃; for 2h; chemoselective reaction; | |
Multi-step reaction with 2 steps 1: thionyl chloride; pyridine / dichloromethane 2: dimethylsulfoxide-d6 / 35 °C / Irradiation | ||
With Iron(III) nitrate nonahydrate; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In acetonitrile at 20℃; for 2h; Inert atmosphere; Green chemistry; | 2.Representative procedure for the tandem oxidative amidation of benzyl alcoholswith amine hydrochloride salts General procedure: Amixture of Fe(NO3)3.9H2O (20 mg, 0.05 mmol,5.0 mol %), TEMPO (15.6 mg, 0.10 mmol, 10 mol %) and benzyl alcohol (1.0 mmol,1 equiv) in acetonitrile (1.0 mL) was stirred under open air at roomtemperature (ca 23 oC) for 2 h. Amine hydrochloride salt (1.2 mmol,1.2 equiv), powdered CaCO3 (110 mg, 1.1 mmol, 1.1 equiv) and TBHP(70 wt% in H2O, 0.16 mL, 1.1 mmol, 1.1 equiv) were added sequentiallyto the mixture. The reaction vessel was capped and allowed to stir at 60 oCfor 16 h. After cooled to room temperature, the volatiles were removed under reducedpressure and the crude product was purified by flash chromatography on silicagel by gradient elution of ethyl acetate in petroleum ether to obtain the amideproduct. All amides were identified by full spectroscopic characterization andcomparison with literature or analogous literature data. | |
163.8 mg | With 5-nitro-3-oxo-1λ3-benzo[d][1,2]iodaoxol-1(3H)-yl acetate In N,N-dimethyl-formamide at 60℃; for 24h; | |
96 %Chromat. | With Isopropenyl acetate; C16H21ClIrNO In toluene at 80℃; for 10h; Inert atmosphere; | General Procedure for the Hydrogen Transfer Oxidation of Benzylic Primary Alcohols Shown in Table 4 General procedure: Under an atmosphere of argon, catalyst 2e (2.0 mol%), benzylic primary alcohol (1.0 mmol), isopropenyl acetate (1.0 mmol), and toluene (18 mL) were placed in a flask. The mixture was stirred at 80 °C for 10 h. The conversion of benzylic primary alcohol and the yield of benzaldehyde derivative were determined by GC analysis using biphenyl as an internal standard. |
With sodium hypochlorite; potassium bromide In dichloromethane; water at 5℃; for 0.166667h; | ||
With 5-nitro-3-oxo-1λ3-benzo[d][1,2]iodaoxol-1(3H)-yl acetate In N,N-dimethyl-formamide at 60℃; for 24h; | ||
91 %Chromat. | With (carbonyl)(chloro)(hydrido)tris(triphenylphosphine)ruthenium(II); oxygen In toluene at 90℃; for 18h; Molecular sieve; Sealed tube; | |
90 %Chromat. | With C39H29N5ORu(2+)*2ClO4(1-); dihydrogen peroxide In water; acetonitrile at 70℃; for 12h; Reflux; | |
With oxygen In toluene at 100℃; for 0.116667h; Green chemistry; | ||
With tert.-butylhydroperoxide at 70℃; for 8h; | ||
96 %Spectr. | With bismuth(III) vanadate; oxygen In acetonitrile at 40℃; for 24h; Schlenk technique; Irradiation; | 2.4. Photocatalytic reactions General procedure: Bismuth vanadate (32.3 mg, 100 mmol) was added to a Schlenkflask containing benzyl alcohol stock solution (1 mL, 0.1 mmol inacetonitrile) and acetonitrile (9 mL). The mixture was left to stirfor 30 min to disperse the catalyst under a dioxygen atmospherevia a balloon. The mixture was then irradiated with a 30W blueLED array at a distance of 2 cmwith an irradiance of 245mWcm2.The mixture reached ca. 40 °C by the end of the reaction and afterirradiation, the catalyst was removed using centrifugation at4000 rpm for 30 min. For GC analysis, 1 mL of supernatant wastaken and 1 lL injected. For NMR analysis, the supernatant wasreduced in volume using a rotary evaporator at 65 mbar at 20 °C,and the residue dissolved in d6-DMSO containing maleic acid asan internal standard. |
With oxygen In toluene at 100℃; for 0.1h; | ||
46 %Spectr. | With 2BF4(1-)*C21H37IrN2O3(2+) In toluene; <i>tert</i>-butyl alcohol for 72h; Schlenk technique; Inert atmosphere; Reflux; | |
With fluorosulfonyl fluoride; potassium carbonate; dimethyl sulfoxide at 20℃; for 12h; | ||
With sodium hypochlorite; 4-amino-2,2,6,6-tetramethyl-1-piperidine-1-oxyl; sodium hydrogencarbonate; sodium bromide In water at 0℃; for 0.0333333h; | ||
26 %Chromat. | With oxygen; 6C68H44ClMnN12*8Zn(2+)*12C2F6NO4S2(1-)*4F6P(1-); Flavin mononucleotide; NADH In water; N,N-dimethyl-formamide; acetonitrile at 35℃; for 10h; | |
With oxygen at 100℃; for 0.183333h; Green chemistry; | ||
With pyridinium chlorochromate In dichloromethane | General procedure for the synthesis of aldehyde intermediates General procedure: To a solution of methyl phenyl acetates (1.0 eq.) in dry THF (5mL) was added LiAlH4 (2 eq.) at 0°C under N2 atmosphere, and the resulting mixture was stirred at room temperature for 1h [23]. After complete consumption of starting material, the reaction mixture was quenched with Na+/K+ tartrate solution (∼10mL), and the mixture was filtered after being stirred at room temperature overnight. The collected filtrate was dried and concentrated to afford crude alcohol intermediate, which was oxidized by PCC (2 eq.) for 2h in CH2Cl2 (5-10mL) [24,25]. The reaction mixture was filtered through short silica column to remove brown side-product. The collected filtrate was concentrated in vacuo for next step without any purification. | |
With 1-methyl-1H-imidazole; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; [CuI3(CuII(N,N‘-(butane-1,4-diyl)bis(1-(1H-imidazol-4-yl-1-ido)methanimine)))3]·3ClO4 In acetonitrile at 20℃; for 2h; | ||
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; [bis(acetoxy)iodo]benzene In dichloromethane at 20℃; for 0.5h; Inert atmosphere; | Transformation of Primary Alcohols 1 into Diethyl 3-Aryl- or 3-Alkylisoxazole-4,5-dicarboxylates 4; Typical Procedure General procedure: DIB (354.0 mg, 1.1 mmol) was added to a solution of p-methylbenzyl alcohol 1A (122.2 mg, 1.0 mmol) and TEMPO (15.6 mg, 0.1 mmol) in CH2Cl2 (2.0 mL). The mixture was stirred at r.t. under Ar atmosphere. After 30 min, NH2OH·HCl (104.2 mg, 1.5 mmol) and K2CO3 (103.7 mg, 0.75 mmol) were added and the obtained mixture was stirred for 18 h at r.t. Then, DMF (0.2 mL) and NCS (200.1 mg, 1.5 mmol) were added to the solution at 0 °C. After 1 h, the reaction mixture was stirred for 3 h at r.t., then Et3N (209.1 L, 1.5 mmol) and diethyl acetylenedicarboxylate (238.5 L, 1.5 mmol) were added to the solution and the obtained mixture was stirred for 1 h at r.t. The mixture was quenched with sat. aq. NaHCO3 and extracted with CHCl3 (3 × 10.0 mL), and the organic layer was dried over Na2SO4. After removal of the solvent, purification by short column chromatography on silica gel (hexane/ EtOAc, 8:1) gave diethyl 3-(p-methylphenyl)isoxazole-4,5-dicarboxylate 4A (266.9 mg, 88%). | |
With oxygen; BiCdVO5 In acetonitrile at 20℃; for 12h; Irradiation; Sealed tube; | ||
With 1-methyl-1H-imidazole; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; oxygen In acetonitrile at 20℃; for 2h; | ||
With tert.-butylnitrite; oxygen In acetonitrile at 25℃; for 12h; Green chemistry; | ||
99 %Spectr. | With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; oxygen; acetic acid; sodium nitrite at 20℃; for 0.666667h; | |
With oxygen; C54H60N6O6Pd(2+)*2Br(1-); potassium carbonate In toluene at 80℃; for 8h; Autoclave; | ||
With caesium carbonate In 1,3,5-trimethyl-benzene at 150℃; for 24h; | ||
With nitric acid In 1,4-dioxane at 90℃; for 2h; Schlenk technique; | 2.4. Catalytic benzyl alcohol oxidation General procedure: The standard benzyl alcohols oxidation was performed, if nototherwise stated, as follows. 0.25 mmol of the alcohol was dissolved,in a 4 mL Schlenck-type tube, in 0.5 mL of 1,4-dioxane.Then, the adequate amount of oxMWNT was added to reach a catalystloading of 5 %wt., and finally, 0.5 mmol of HNO3 was added tothe mixture. The reactor was closed and the temperature raised to90 C, where reaction was maintained with magnetic stirring for adesired time, typically 2 h [26]. A 0.05 mL aliquot was withdrawnand analyzed by NMR methods to track the evolution of theoxidation. | |
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; oxygen; triethylamine In water at 80℃; for 15h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | Stage #1: triallyl(phenyl)silane With tetrabutyl ammonium fluoride In water; dimethyl sulfoxide at 20℃; for 1h; Stage #2: 4-bromobenzenemethanol With tricyclohexylphosphine In water; dimethyl sulfoxide at 80℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With C20H20N2O2Pd; sodium hydrogencarbonate In water at 80℃; for 6h; | |
98% | With trans-di(μ-acetato)bis[o-(di-o-tolylphosphino)benzyl]dipalladium(II); potassium carbonate In water for 0.5h; Sealed tube; Inert atmosphere; Reflux; | |
98% | With palladium diacetate; potassium carbonate In water; isopropyl alcohol at 20℃; for 0.25h; | Typical experimental procedure: General procedure: In a 50 mL round bottomed flask, a mixture ofaryl halide (1 mmol), arylboronic acid (1.2 mmol), Pd(OAc)2 (1 mol %), biuret (0.01 mmol) and K2CO3 (2 mmol) in iPrOH/H2O (1:1, v/v, 4 mL) and the mixture was stirred at room temperature for a time period as mentioned in Table 2. The progress of the reaction was monitored by TLC. After completion of the reaction it was extracted with diethyl ether (3 x 10 mL) and washed with water. The combined ether extract was dried over anhydrous Na2SO4. The filtrate was concentrated under reduced pressure. The product was purified by column chromatography over silica gel using hexane/ethyl acetate (9:1 v/v) to get the desired coupling product. The products were characterized by IR, 1H NMR, 13C NMR and GC-MS. |
97% | With palladium diacetate; potassium carbonate; urea In water; isopropyl alcohol at 20℃; for 0.333333h; Green chemistry; | Typical experimental procedure: General procedure: In a 50mL round bottomed flask, a mixture of aryl halide (1mmol), arylboronic acid (1.2mmol), Pd(OAc)2 (1mol%), urea (0.01mmol) and K2CO3 (3mmol) in iPrOH/H2O (1:1, v/v, 4mL) and the mixture was stirred at room temperature for a time period as mentioned in Table 2. The progress of the reaction was monitored by TLC. After completion of the reaction it was extracted with diethyl ether (3×10mL) and washed with water. The combined ether extract was dried over anhydrous Na2SO4. The filtrate was concentrated under reduced pressure. The product was purified by column chromatography over silica gel using hexane/ethyl acetate (9:1 v/v) to get the desired coupling product. The products were characterized by IR, 1H NMR, 13C NMR and GC-MS. |
96% | With palladium diacetate; caesium carbonate In toluene at 110℃; for 1h; Inert atmosphere; | |
95% | With potassium carbonate for 4.5h; | General procedure for synthesis of biphenyl derivatives General procedure: A mixture of NaPh4B (0.5 mmol), phenylboronic acid (1 mmol) or triphenyltin chloride (Ph3SnCl) (0.5 mmol) plus aryl halide (1 mmol), base (K2CO3, 3 mmol) and Pd-ABA-MCM-41 (8 mg, 1.3 mol%) as catalyst in PEG (poly(ethylene glycol)) solvent was stirred at 80 °C for the required time. The progress of the reaction was monitored by TLC. After completion of the reaction, the mixture was cooled to room temperature, then the catalyst was separatedby filtration, and solvent was evaporated. The products were extracted with diethyl ether and water. The solvent was evaporated to give the product. |
94% | With C49H74N4O34Pd(2+)*2C2H3O2(1-); sodium carbonate In water for 6h; Sealed tube; Reflux; Green chemistry; | |
94% | With Pd(L-proline)<SUB>2</SUB>; potassium carbonate In water for 4h; Sealed tube; Reflux; | |
94% | With potassium carbonate at 100℃; for 6h; | |
93% | With Pd(2-(4-bromophenyl)pyridine)(IMes)Cl; caesium carbonate In 1,4-dioxane at 110℃; for 18h; Inert atmosphere; | |
93% | With C34H30ClN3O2Pd; potassium carbonate In 2-methyl-propan-1-ol at 110℃; for 10h; Inert atmosphere; Schlenk technique; | 11 preparation of Biphenyl-4-methanol Under the protection of high pure nitrogen gas, into 10ml of Schlek reaction tube was added 0.05mmol of biarylpyridine cyclopalladium nitrogen heterocyclic carbene compound (1), 1.0mmol 4-Bromobenzyl alcohol, 3.0 mmol of phenylboronic acid, 6 mmol of potassium carbonate and 5 ml of isobutyl alcohol, the reaction tube was replaced with nitrogen three times and then heated to 110 °C using an oil bath under magnetic stirring and the reaction was refluxed for 10 hours. The oil bath was removed and the reaction solution was concentrated using a rotary evaporator. The remaining residue was separated by Silica gel thin layer chromatography with ethyl acetate as the developing solvent to obtain pure product biphenyl-4-methanol, yield 93%. |
93% | With sodium t-butanolate In water at 28℃; for 6h; Irradiation; | 2.2 A typical procedure for the photocatalytic reactions General procedure: Aryl iodide (1 mmol), aryl boronic acid (1.2 mmol), nano Pd/TiO2 (15 mg), H2O-PEG (5 mL, volume ratio of 1:1), NaOC(CH3)3 (3 mmol) were placed in a 10 mL Pyrex round bottom flask. The flask was covered with a rubber stopper. The reaction vessel was stirred at ambient temperature (28 °C) under visible light obtained by irradiation of 15 W flexible white LED strips placed on the walls inside the box spirally and the reaction flask was placed in the center of the box (see SM, S1). The temperature of the reaction system was kept at ambient temperature with an air conditioner and a mechanical fan mounted on the box. After completion of the reaction (monitoring by GC), the catalyst was removed by centrifuging and the resulting mixture was extracted with AcOEt (2×10 mL). The organic layers were combined and dried over anhydrous sodium sulfate (Na2SO4) and further concentrated under reduced pressure. The desired product was purified by column chromatography (CC) on silica gel using n-hexane/ethyl acetate (40:1, 20:1). |
93% | With potassium carbonate In ethanol; water at 70℃; for 0.5h; | 2.4 General Procedure for Suzuki-Miyaura Coupling Reaction General procedure: Aryl halide (1 mmol), K2CO3(2.0 mmol), phenylboronicacid (1.2 mmol), click-catalyst A (0.2 mol%) and 3 mLH2O/EtOH (1:1, V/V) were mixed in a round-bottom flaskequipped with condenser and under an air atmosphere. Themixture was heated in an oil bath at 70 °C (for the aryl bromides)and stirred continuously during the reaction andmonitored by thin-layer chromatography (TLC) and gaschromatography (GC). After the reaction was complete, themixture was diluted with EtOH. The catalyst was separatedby centrifugation, washed with EtOH/H2O and then reusedfor recycling experiments without further pretreatment.Then, the coupled product was extracted with EtOAc andthe organic phase was dried over MgSO4,filtered and concentrated.The residue was purified by recrystallization orsilica gel column chromatography (n-hexane:EtOAc), andwas characterized. |
91% | With tetra-butylammonium acetate In ethanol for 0.25h; microwave irradiation; | |
90% | With C22H32Cl2N4Pd; potassium carbonate In methanol; water at 20℃; for 0.25h; | |
86% | With N<SUP>2</SUP>,N<SUP>4</SUP>,N<SUP>6</SUP>-tridodecyl-1,3,5-triazine-2,4,6-triamine; potassium carbonate; palladium dichloride In water at 80℃; for 12h; | |
86% | With sodium tetrahydroborate; potassium carbonate; triphenylphosphine In dimethyl sulfoxide at 25℃; for 0.166667h; Inert atmosphere; | |
65% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In N,N-dimethyl-formamide at 100℃; for 0.5h; Inert atmosphere; | |
62.4% | With potassium carbonate In ethanol at 20℃; for 6h; | |
With potassium carbonate In 1,2-dimethoxyethane at 80℃; for 16h; | ||
80 % Chromat. | With caesium carbonate In N,N-dimethyl-formamide at 100℃; for 16h; | |
With potassium carbonate In ethanol; water at 60℃; for 12h; | 2 Para-bromobenzaldehyde (0.5 mmol), which is widely commercially available, was added to 3 ml of tetrahydrofuran (THF), that mixture was then added to a water mixture. At that point XAD-4 resin (500 mg) was added to the mixture and was cooled to 0° C., then NaBH4 (0.6 mmol) was added. After stirring for thirty minutes, the mixture was filtered with a porosity M filter, commercially available from Chemglass, in Vineland, N.J., as part number CG-1406-47. Filtration was to collect the resin. The collected resin was washed with water. The collected resin was added to a solution of phenyl boric acid (0.8 mmol) and K2CO3 (1.0 mmol) in a water/ethanol (2:1) solution. Next, Pd(PPh3)4 (0.01 mmol) was added and the reaction mixture was heated at 60° C. for 12 hours. Next, the mixture was filtered and washed with water, as above. The collected resin was washed with about 40 ml of acetone in order to dislodge the product which is biphenyl-methyl alcohol. | |
93 %Chromat. | With potassium carbonate In 1,4-dioxane for 1h; Inert atmosphere; Reflux; | General procedure for Suzuki cross-coupling reactions General procedure: Under N2 atmosphere, an around-bottomed flask was charged with aryl halide (1.0 mmol), phenylboronic acid (1.2 mmol), K2CO3 (2.0 mmol), dioxane (5 mL), catalyst 3b (Pd 0.05 mol %) and n-Decane (0.9 mmol, the internal standard). The mixture was heated to reflux for the indicated time and the reaction progress was monitored by GC. After the reaction completed, the catalyst was filtered-off from the reacted mixture, washed with water, ethanol and acetone and dried overnight at 60 °C in a drying oven for the next cycle. |
90 %Chromat. | With potassium carbonate In water at 65℃; for 8h; Inert atmosphere; Green chemistry; | |
99 %Chromat. | With PdCl2{κ2−N,S−2−(4,5-dihydrothiazol-2-yl)aniline}; potassium carbonate In methanol at 70℃; for 0.5h; Reflux; | 2.9. Typical procedure for the coupling reactions between aryl bromides andboronic acid General procedure: The round-bottom flask was placed with the appropriate amount ofcatalyst, and 5 mL of methanol was added to it. After stirring for 5 min,aryl bromide (0.5 mmol), phenylboronic acid (0.55 mmol), and K2CO3(1 mmol) were introduced into the reaction flask. The mixture washeated at 60 °C for the required time (the course of reaction wasmonitored by GC analysis), following which the solvent was removedunder reduced pressure. The residue was diluted with water (8 mL) andEtOAc (8 mL) followed by extraction twice (2-6 mL) with EtOAc. The combined organic fractions were dried (MgSO4), stripped of the solventunder vacuum, and the residue was dissolved in 5 mL of dichloromethane.An aliquot was taken with a syringe and subjected to GC analysis. Yields were calculated versus aryl bromides as an internalstandard. |
With palladium 10% on activated carbon In methanol at 65℃; for 5h; | 1 First monomer synthesis (Biphenyl-4-methanol, PC-423) PHBA (Phenylboronic acid) and 4-BBA (4-Bromobenzyl alcohol) were used as raw materials, Pd / C 10% was used as a catalyst and methanol was used as a solvent. The first monomer (PC-423) was obtained through a reflux reaction at a temperature of 65 °C for about 5 hours. At this time, 1.0 to 1.20 equivalents of PHBA (phenylboronic acid) was used based on 1 equivalent of 4-BBA (4-Bromobenzyl alcohol) and the Pd / C 10% catalyst was used in an amount of 0.04 to 0.10 equivalents based on 1 equivalent of 4-BBA (4-Bromobenzyl alcohol) then the reaction was continued until the 4-BBA (4-Bromobenzyl alcohol) was completely reacted. | |
94 %Spectr. | With C32H27Cl2N3Pd; potassium carbonate In ethanol; water at 45℃; for 0.25h; Sealed tube; | |
86 %Chromat. | With C56H52N12O12Pd4S4; potassium carbonate In ethanol; water at 70℃; for 0.666667h; | |
93 %Spectr. | With C28H25N5O4PdS2; potassium carbonate In ethanol; water at 100℃; | 2.4. Suzuki-Miyaura coupling experiment General procedure: In a typical catalytic reaction, (4-bromophenyl)methanol (0.19 g,1.0 mmol), benzeneboronic acid (0.15 g, 1.2 mmol), K3CO3 (0.14 g,1.0 mmol) and preformed complex (0.2 mol % relative to (4-bromophenyl)methanol) were added together in a 10mL roundbottomflask equipped with magnetic stirrer bar. In the case of insitu, 0.2 mol % Pd(AcO)2 and 0.4 mol % ligand were used relative to(4-bromophenyl)methanol. Water (4 mL) was added and themixture refluxed on an oil bath set at 100 C for the desired reactiontime. An aliquot of the reaction mixture was taken into a 10 mLconical flask which was dried under vacuum to exclude the solvents.The residue was subjected to 1H NMR measurement usingdeuterated DMSO. The reactivity of the catalyst was evaluated bycomparison of the NMR signals for the methylene (eCH2e) protonsof (4-bromophenyl)methanol at dz4.4 ppm with that of the correspondingbiphenyl product at dz4.6 ppm. The yields wereestimated by determining the integral of the product peak as apercentage of the sum of all observed methylene signals [57]. |
62 %Spectr. | With C54H30Br2Cl4N4Pd2S2; potassium carbonate In ethanol; water at 40℃; for 3h; Sealed tube; High pressure; | 2.5. Catalysis experiments and characterization of biphenyl products General procedure: Except for the few higher temperature catalysis experiments,which were carried out under reflux conditions, the ambient conditioncatalysis runs were routinely conducted in sealed glass vialsmaintained at 40-50 C by thermostated oil baths equipped withmagnetic stirrers. The substrates boronic acid (1 mmol) and arylbromidereagents (1 mmol) were coupled in the presence of a baseadditive (1.2 eq.) and palladium catalyst material (0.2 mol %) usingwater / ethanol mixture (1:3) as reaction media. After the desiredduration, an aliquot of the resultant reaction mixture is transferredto a clean vial. The solvent mixture is evaporated under high vacuumsuction pressure with cooling trap in place after which theresidue is collected in deuterated dmso and transferred into anNMR tube. Yields were routinely estimated by comparison of theNMR signal of the methylene functions on bromophenymethanoland that on the biphenyl coupling product. The catalysis product1-(40-(hydroxymethyl)-[1,10-biphenyl]-4-yl)ethan-1-one has beenisolated and characterized [28]. Other new catalysis products werealso analysed |
97 %Spectr. | With C29H34N4O4PdS2; potassium carbonate In water at 60℃; for 0.5h; Green chemistry; | Catalysis Experiments General procedure: In a typical in situ catalyst generation approach for the C-C coupling reaction, (4-bromophenyl)methanol (0.19 g, 1.0 mmol), phenylboronic acid (0.46 g, 1.2 mmol), K2CO3 (0.14 g, 1.0 mmol), Pd(OAc)2 (0.2 mol-% relative to the aryl bromide), and a given ligand (0.4 mol-%) were weighed into a 10 mL round-bottom flask equipped with a magnetic stirrer and reacted in water (4 mL) for a given reaction duration. In the case of a preformed palladium(II) complex, 0.2 mol-% equivalent relative to the aryl bromide was used in place of the ‘Pd(OAc)2+ligand’ deployed for the in situ complex generation. After the reaction, an aliquot of the reaction mixture was transferred into a clean conical flask and the solvent was removed under vacuum. The residue was collected in deuterated DMSO and its 1H NMR spectrum analysed. The yields were evaluated by comparing integration values for the NMR signal for the methylene CH2 protons of (4-bromophenyl)methanol at ~4.4 ppm against the CH2 function of the resulting biphenyl products at ~4.7 ppm (see Fig. S1 in the Supplementary Material for illustration).[59,60] The biphenyl products have been characterised in our previous studies.[19,59,61] |
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; triethylamine In water at 60℃; for 6h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With dmap; benzotriazol-1-ol; dicyclohexyl-carbodiimide In tetrahydrofuran at 25℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99.5% | With silica-supported Jones reagent In dichloromethane for 0.035h; | |
96% | With diethylene glycol dimethyl ether at 70℃; for 0.583333h; Sonication; | 16 Example 16: Preparation of 4-phenylbenzoic acid: In a 10 mL round bottom flask, 0.85 g of 4-hydroxymethylbiphenyl (4-phenylbenzyl alcohol) and 2 g of diethylene glycol dimethyl ether were sequentially added, and the resulting mixture was subjected to an ultrasonic reaction apparatus at 40 KHz/30 W/70. °C Ultrasonic radiation was allowed to open for 35 minutes. The diethylene glycol dimethyl ether was removed under reduced pressure, and recrystallized to give 0.95 g of 4-phenylbenzoic acid, yield 96%. |
89% | With sodium tetrahydridoborate; 1% Pd/C; water monomer; potassium hydroxide In methanol at 20℃; for 6h; In air; |
81% | Stage #1: biphenyl-4-yl methanol With ((CH3C6H4CH(CH3)2)RuI(C6H4NC3H2NCH3)); potassium hydroxide In 1,3-dimethylbenzene for 6h; Schlenk technique; Reflux; Stage #2: With hydrogenchloride In water monomer; 1,3-dimethylbenzene Schlenk technique; | |
80% | With potassium hydroxide In toluene at 120℃; for 24h; | 2.3 General procedure for the dehydrogenation of benzylic alcohols General procedure: Benzylic alcohols (1.0mmol), solid 1a (0.2-2mol %), KOH (2-4 equiv.) and 1.5mL toluene were charged sequentially in a 25mL tube with a magnetic bar. The reaction tube was stirred at 120°C for 12-48h attached with an open bubbler. After the certain reaction time, water (5mL) was added, and the mixture was extracted with diethyl ether (3×5mL). Then the aqueous phase was acidified with HCl (6M) and further extracted with ethyl acetate (3×10mL). The combined ethyl acetate solution was washed with brine (15mL), dried over anhydrous Na2SO4, and evaporated to dryness under reduced pressure, the pure acids was obtained and weighted for calculating the yield. |
76% | With manganese(II) bromide; anhydrous silver carbonate; potassium hydroxide In 1,3,5-trimethyl-benzene at 50 - 165℃; for 8h; Schlenk technique; Inert atmosphere; | |
62% | With potassium hydroxide; zinc oxide In 1,3,5-trimethyl-benzene at 164℃; for 18h; Inert atmosphere; Schlenk technique; | |
49% | Stage #1: biphenyl-4-yl methanol With [RuCl2(p-cymene)(iPr2-imy)]; tricyclohexylphosphine tetrafluorohydroborate; potassium hydroxide In toluene for 6h; Schlenk technique; Inert atmosphere; Reflux; Stage #2: With hydrogenchloride In water monomer | |
Multi-step reaction with 2 steps 1: tert.-butylnitrite; oxygen / acetonitrile / 12 h / 25 °C / 760.05 Torr / Green chemistry 2: oxygen / acetonitrile / 24 h / 80 °C / 760.05 Torr / Green chemistry | ||
Multi-step reaction with 2 steps 1: chloro(η6-p-cymene)[2-(2,6-diisopropylphenyl)-5-(1,3-diisopropyl-2,4,6-trioxohexahydropyrimidin-5-yl-κC5)imidazo[1,5-a]pyridin-3-ylidene-κC3]ruthenium(II); potassium hydroxide / dichloromethane; o-dimethylbenzene / 150 °C / Schlenk technique 2: hydrogenchloride / water monomer / pH 2 / Schlenk technique |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96.7% | With thionyl chloride; potassium carbonate In methanol; water; ethyl acetate; N,N-dimethyl-formamide | 2 (+)-N,N-dimethyl-(6-(4-biphenylyl)methoxy-2-tetralin)acetamide EXAMPLE 2 (+)-N,N-dimethyl-(6-(4-biphenylyl)methoxy-2-tetralin)acetamide 378.6 g of 4-hydroxymethylbiphenyl was dissolved in 1133 ml DMF, and 177.6 mL thionyl chloride was added dropwise thereto at an internal temperature of 20° C. or less. The mixture was reacted at room temperature for 1.5 hours. 2267 mL ethyl acetate was added to the reaction solution and cooled at 10° C., and 1133 mL tap water was added dropwise at 20° C. or less. The organic layer was separated and washed with 1133 mL of 10% aqueous sodium carbonate, 1133 mL of 5% aqueous sodium bicarbonate and 1133 mL water in this order. The organic layer was separated and concentrated under reduced pressure until the amount of the remaining solution became 763 g, then 872 mL DMF was added thereto, and the reaction solution was concentrated under reduced pressure to distill the remaining ethyl acetate away, whereby 1286 g solution of 4-chloromethylbiphenyl in DMF (content, 32.1%; yield, 99.1%) was obtained. 435.9 g (+)-N,N-dimethyl-(6-hydroxy-2-tetralin)acetamide, 516.4 g potassium carbonate and 436 mL DMF were added thereto and stirred for 3 hours at an internal temperature of 80° C. under a nitrogen atmosphere. 1308 mL methanol was added to the reaction solution, 1744 mL water was added thereto at an internal temperature kept at about 60° C., and the mixture was stirred at 60° C. for 30 minutes. Then, the reaction mixture was stirred at 40° C. for 1 hour, and the precipitated crystals were collected by filtration and washed with 1744 mL methanol and then twice with 2180 mL water previously heated at 40° C. By drying the product at 50° C. under reduced pressure, the title compound, 726.8 g (yield 96.7%), was obtained as pale yellow crystals. 1H-NMR (300 MHz, CDCl3) δ: 1.42-1.48(1H, m), 1.97-2.04(1H, m), 2.30-2.47(4H, m), 2.79-2.91(3H, m), 2.97(3H, s), 3.01(3H, s), 5.06(2H, s), 6.73-6.78(2H, m), 6.97 (1H, d, J=8.3 Hz), 7.34-7.62(9H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With sodium azide; [bis(acetoxy)iodo]benzene In acetonitrile at 0 - 80℃; for 36h; Inert atmosphere; |
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 |
---|---|---|
76% | With bis(tricyclohexylphosphine)nickel(II) dichloride; methylmagnesium bromide; 1,2-bis-(dicyclohexylphosphino)ethane In dibutyl ether; toluene at 60℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 93% 2: 7 %Spectr. | With Iron(III) nitrate nonahydrate; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; potassium chloride; oxygen In 1,2-dichloro-ethane at 25℃; for 48h; Schlenk technique; | General procedure: To a Schlenk tube were added Fe(NO3)3·9H2O (40.6 mg, 0.1 mmol), TEMPO (15.8 mg, 0.1 mmol), KCl (7.5 mg, 0.1 mmol), 1a (108.5 mg, 1.0 mmol), and DCE (4.0 mL) sequentially under an atmosphere of oxygen (gas bag, commercial size: 2 L, which could be expanded to 5 L). The mixture was then stirred at 25 °C until completion of the reaction as monitored by TLC (petroleum ether/EtOAc = 5:1) (48h). The crude reaction mixture was filtered through a short column of silica gel (height: 2 cm, diameter: 3 cm) eluting with Et2O (3 × 25 mL). After evaporation, the residue was purified by chromatography on silica gel [petroleum ether/EtOAc = 15:1 (500 mL) to 2:1 (300 mL)] to afford benzoic acid (2a)14 (69.9 mg, 57%) as a pale yellow solid. Yields of 57% of 2a and 38% of benzaldehyde (3a)15 were observed by NMR analysisof the crude product using CH2Br2 as an internal standard and by comparison with spectra reported in the literature. |
1: 32 %Chromat. 2: 5 %Chromat. | With sodium hypochlorite In 1,2-dimethoxyethane; water at 20℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60 % de | Stage #1: 2,2'-dipyridyl carbonate; biphenyl-4-yl methanol With dmap In dichloromethane at 20℃; for 5h; Inert atmosphere; Stage #2: 2-amino-3-hydroxy-4-methylpentanoic acid With sodium hydrogencarbonate In tetrahydrofuran; water at 20℃; for 15h; Microwave irradiation; Overall yield = 0.06 g; | 51.3; 51.4; 52.5 Preparation of (2R*,3R*)- and (2R*,3S*)-3-hydroxy-4-methyl-2-[(4-phenylphenyl)methoxycarbonylamino]pentanoic acid To a stirred diastereomeric mixture containing (2R*,3R*)- and (2R*,35'*)-2-amino- 3-hydroxy-4-methyl-pentanoic acid (0.05 g, 0.34 mmol) and NaHC03 (0.03 g, 0.34 mmol) in H20 (2.0 mL), at rt, the isomeric mixture containing (4-phenylphenyl)-methyl-2-pyridyl carbonate and (4-phenylphenyl)-methyl-2-oxopyridine-l-carboxylate (0.45 g, 1.48 mmol) [prepared as for example 17, step 1] THF (2.0 mL) was added. After 15 h at rt, the crude mixture was rotary evaporated to remove the organics and subsequently extracted with Et20 (3x10 mL). The aqueous phase was acidified with 2.0 M HC1 solution to pH 2-3 and subsequently extracted with AcOEt (3x20 mL). The organic fraction was dried over Na2S04, filtered and concentrated to dryness to afford the title compound (0.06 g, 50% over 2 steps), as a diastereoisomeric mixture (anti.syn = 8:2), as an off-white solid, which was used in the next step without further purification. MS (ESI) m/z: 358 [M-H]+; (ESI) m/z: 356 [M-H]-.1HNMR (DMSO-d6) δ 0.82 (d, J = 6.55 Hz, 3H), 0.88 (d, J = 6.92 Hz, 3H), 1.62 - 1.79 (m, 1H), 3.17 (dd, J= 2.87, 9.15 Hz, 1H), 3.51 (d, J= 9.16 Hz, 1H), 5.05 (s, 2H), 7.32 - 7.41 (m, 1H), 7.41 - 7.52 (m, 4H), 7.66 (td, J= 1.74, 6.70, 7.42 Hz, 4H) (reported data refer to the major anti diastereoisomer). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 2,2'-dipyridyl carbonate; biphenyl-4-yl methanol With dmap In dichloromethane at 20℃; for 5h; Inert atmosphere; Stage #2: 2-amino-3-hydroxy-4-methylpentanoic acid With sodium hydrogencarbonate In tetrahydrofuran; water at 20℃; for 15h; Inert atmosphere; Overall yield = 0.21 g; | 17.1; 56.3; 56.4; 57.4 Preparation of (2R*,3R*)- and (2R*,3S*)-3-hydroxy-4,4-dimethyl-2-[(4-phenyl- phenyl)-methoxy-carbonylamino]-pentanoic acid To a stirred diastereomeric mixture containing (2R*,3R*)- and (2R*,3S*)-2-amino- 3-hydroxy-4,4-dimethyl-pentanoic acid (0.288 g, 1.78 mmol) and NaHC03 (0.15 g, 1.8 mmol) in H20 (7.0 mL), at rt, the isomeric mixture containing (4-phenylphenyl)-methyl-2- pyridyl carbonate and (4-phenylphenyl)-methyl-2-oxopyridine-l-carboxylate (0.82 g, 2.68 mmol) [prepared as for example 17, step 1] THF (7.0 mL) was added. After 15 h at rt, the crude mixture was rotary evaporated to remove the organics and subsequently extracted with Et20 (3x10 mL). The aqueous phase was acidified with 2.0 M HC1 solution to pH 2-3 and subsequently extracted with AcOEt-(3x20 mL). The organic fraction was dried over Na2S04, filtered and concentrated to dryness to afford the title compound (0.21 g, 32% over 2 steps), as a diastereoisomeric mixture (anti.syn = 9:1), as an off-white solid, which was used in the next step without further purification. MS (ESI) m/z: 410 [M-K]+; (ESI) m/z: 370 [M-H]-. 1H NMR (DMSO-d6) δ 0.88 (s, 9H), 3.40 (d, J = 7.37 Hz, 1H), 4.09 - 4.18 (m, 1H), 5.08 (s, 2H), 5.08 (s, broad, 1H), 7.33 - 7.53 (m, 5H), 7.60 (d, J = 8.97 Hz, 1H), 7.63 - 7.72 (m, 4H), 12.21 (s, 1H) (reported data refer to the major anti diastereoisomer). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.01 g | Stage #1: 2,2'-dipyridyl carbonate; biphenyl-4-yl methanol With dmap In dichloromethane at 0 - 20℃; for 5h; Inert atmosphere; Stage #2: 2-amino-3-hydroxy-4-methylpentanoic acid With sodium hydrogencarbonate In tetrahydrofuran; water at 20℃; for 15h; Microwave irradiation; Stage #3: With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine In dichloromethane at 0 - 20℃; for 16h; Inert atmosphere; | 51.3; 51.4; 52.5; 52.6 Preparation of (4-phenylphenyl)-methyl-N-[(2R*,3R*)-2-isopropyl-4-oxo-oxetan-3-yl]carbamate Under nitrogen atmosphere, to a stirred mixture of (2R*,3R*)-3-hydroxy-4-methyl- 2-[(4-phenylphenyl)-methoxy-carbonylamino]-pentanoic acid and (2R*,3S*)-3-hydroxy-4- methyl-2-[(4-phenylphenyl)-methoxy-carbonylamino]-pentanoic acid (0.059 g, 0.17 mmol) in dry CH2C12 (7.0 mL), at 0 °C, Et3N (0.07 mL, 0.5 mmol) and subsequently TBTU (0.065 g, 0.2 mmol) were added. The mixture was left stirring at 0 °C for 1 h and at rt for 15 h. The organics were then removed under reduced pressure, and the resulting crude product purified by column chromatography, using a Teledyne ISCO apparatus, eluting with Cy:AcOEt (from 90:10 to 80:20) to afford the pure title compound (0.01 g, 17%), as pure anti diastereoisomer, as white solid. MS (ESI) m/z: 357 [M-NH4]+; (ESI) m/z: 338 [M-H]- . 1HNMR (DMSO-d6) δ 0.89 (d, J= 6.79 Hz, 3H), 0.97 (d, J= 6.57 Hz, 3H), 1.81 - 2.12 (m, 1H), 4.26 (dd, J= 4.38, 9.1 1 Hz, 1H), 4.80 (dd, J= 4.39, 8.16 Hz, 1H), 5.12 (s, 2H), 7.29 - 7.54 (m, 5H), 7.63 - 7.77 (m, 4H), 8.26 (d, J = 8.21 Hz, 1H). Example 53. 5-Phenylpentyl-N-[(2ly*,3 f*)-2-isopropyI-4-oxo-oxetan-3-yl]-carbamate |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.063 g | Stage #1: 2,2'-dipyridyl carbonate; biphenyl-4-yl methanol With dmap In dichloromethane at 20℃; for 5h; Inert atmosphere; Stage #2: 2-amino-3-hydroxy-4-methylpentanoic acid With sodium hydrogencarbonate In tetrahydrofuran; water at 20℃; for 15h; Inert atmosphere; Stage #3: With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine In dichloromethane at 0 - 20℃; for 16h; | 17.1; 56.3; 56.4; 57.5 Preparation of (4-phenyl-phenyl)-methyl-N-[(2R*,3R*)-2-tert-butyl-4-oxo-oxetan-3- yl]-carbamate Under nitrogen atmosphere, to a stirred mixture of (2R*,3R*)-3-hydroxy-4,4- dimethyl-2-[(4-phenyl-phenyl)-methoxy-carbonylamino]-pentanoic acid and (2R*,3S*)-3- hydroxy-4,4-dimethyl-2-[(4-phenyl-phenyl)-methoxy-carbonylamino]-pentanoic acid (0.203 g, 0.55 mmol) in dry CH2C12 (25 mL), at 0 °C, Et3N (0.23 mL, 1.65 mmol) and subsequently TBTU (0.21 g, 0.66 mmol) were added. The mixture was left stirring at 0 °C for 1 h and at rt for 15 h. The organics were then removed under reduced pressure, and the resulting crude P T/US2012/066421 product purified by column chromatography, using a Teledyne ISCO apparatus, eluting with Cy:AcOEt (from 90: 10 to 80:20) to afford the pure title compound (0.063 g, 58%), as pure anti diastereoisomer, as white solid. MS (ESI) m/z: 371 [M-NH4]+; (ESI) m/z: 352 [M-H]-. 1H NMR (DMSO-d6) δ 0.95 (s, 9H), 4.37 (d, J= 4.64 Hz, 1H), 4.83 (dd, J= 4.65, 8.16 Hz, 1H), 5.14 (s, 2H), 7.32 - 7.56 (m, 5H), 7.60 - 7.75 (m, 4H), 8.25 (d, J= 8.12 Hz, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With potassium hydroxide In water; toluene at 50℃; for 4h; Inert atmosphere; Sealed tube; | General procedures: Under a N2 atmosphere, compounds S1,S3, or S5 (1.0 mmol), KOH (0.8 mL, 25 wt%, ca. 4.5 mmol) were added into a pressure tube at room temperature (rt). The reactant mixture was cooled to -78 oC, then TMSCF2Cl (395 mg, 2.5 mmol) in toluene (2.0 mL) was added. The tube was sealed? and heated at 50 oC for 4 h (NOTE: The reaction conditions were not optimized). After being cooled to rt, the reaction mixture was quenched by adding water (5 ml), and extracted wiyh Et2O (3 x 15 mL). The organic layers were dried over anhydrous MgSO4, concentrated in vacuo, and purified by column chromatography (silica gel; petroleum ether/ethyl acetate) to afford the desired products S2, S4, S6, or S7 (see Table S-1). All the characterization data were in consistence with the previous report [1]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20 mg | With triethylamine In dichloromethane at 0 - 20℃; for 16h; Inert atmosphere; | General Procedure C. General procedure: The appropriate pyrazole (1.0 equiv) was treated with phosgene(20% in toluene) at 0° C. The reaction mixture was stirred at room temperature for 1 h.The solvent was removed under reduced pressure and the crude carbamoyl chloride was redissolved in anhydrous CH2Cl2 (0.5 M). The appropriate amine (1.0 equiv) and Et3N (1.2 equiv) were dissolved in CH2Cl2 and cooled to 0° C. The crude carbamoyl chloride was added dropwise and the reaction mixture was stirred at room temperature for 16 h.The mixture was diluted with EtOAc, washed with saturated aqueous NaCl, and dried over Na2SO4. Evaporation under reduced pressure yielded the crude coupling product that was purified by flash chromatography (SiO2). |
With triethylamine In dichloromethane at 0 - 20℃; for 16h; Inert atmosphere; | 4.1.1. General procedure for pyrazole urea or carbamate synthesis General procedure: The appropriate pyrazole (1.0 equiv) was treated with phosgene (10equiv, 20% in toluene) at 0 °C. The reaction mixture was stirred at roomtemperature for 1 h. The solvent was removed under reduced pressureand the crude carbamoyl chloride was dissolved in anhydrous CH2Cl2(0.5 M). The appropriate amine (1.0 equiv) or alcohol (1 equiv) andEt3N (1.2 equiv) were dissolved in CH2Cl2 (0.5 M) and cooled to 0 °C.The crude carbamoyl chloride was added dropwise and the reactionmixture was stirred at room temperature for 16 h. The mixture wasdiluted with EtOAc, washed with saturated aqueous NaCl, and driedover Na2SO4. Evaporation under reduced pressure yielded the crudecoupling product that was purified by flash chromatography (SiO2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: N,N-dimethyl-formamide; thionyl chloride / dichloromethane / 0 - 20 °C / Schlenk technique; Inert atmosphere 2: copper(l) iodide; 1-methyl-2-azepanone; lithium tert-butoxide; 2,2,6,6-tetramethylheptane-3,5-dione / 12 h / 60 °C / Schlenk technique; Inert atmosphere | ||
Multi-step reaction with 2 steps 1: triethylamine; dmap / tetrahydrofuran / 16 h / 20 °C 2: palladium diacetate; 1,3-bis-(diphenylphosphino)propane; tetrabutyl ammonium fluoride / tetrahydrofuran; 1,4-dioxane / 24 h / 100 °C / Schlenk technique; Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | Stage #1: biphenyl-4-yl methanol With N-benzyl-N,N,N-triethylammonium chloride In toluene Stage #2: acryloyl chloride With 4-methoxy-phenol at 0 - 40℃; for 2h; Stage #3: With sodium carbonate at 80℃; for 2h; | 3 Embodiment 3 To the autoclave, 184 g of 4-phenylbenzyl alcohol, 500 g of toluene and 58.5 g of benzyltriethylammonium chloride were added and stirred to dissolve to give a pale yellow transparent solution. The reaction vessel was then placed in a 0-10 ° C in an ice-water bath. The mixture solution of 117.6g acryloyl chloride and 1g p-hydroxyanisole was slowly dropped into the reactor in 1.5h. After the addition of the dissolved solution, the ice water bath was removed and the reaction vessel was placed in 40 ° C warm water Bath continued to react 2h. Then, 400 g of 40% sodium carbonate solution was added dropwise over 1 h. After the addition, the temperature was raised to 80 ° C and the reaction was continued for 2 h to obtain a reaction product solution. The reaction product solution into the water bath, add 200g of deionized water, stirring lOmin after standing lh, release lower wastewater. Then add 200g mass fraction of 10% potassium chloride solution, stirring lOmin after standing lh, release lower waste water. The reaction product solution after water washing was transferred to a reaction kettle, 0.2 g of p-hydroxyanisole was added and the temperature was controlled to 65 ° C. The water-carrying agent was removed under reduced pressure until the content of the water-carrying agent was less than 500 ppm, Yellow transparent 4-phenylbenzyl acrylate. |
85% | With dmap; triethylamine In dichloromethane at 0 - 20℃; for 6h; | |
60% | With triethylamine In dichloromethane at 0 - 20℃; Schlenk technique; Inert atmosphere; |
421 mg | With triethylamine In dichloromethane at 0 - 20℃; | |
With 4-methoxy-phenol; triethylamine In toluene at 0 - 25℃; for 5.5h; | 3-4 Comparative example 3 In the reactor, add 184 g of 4-biphenylmethanol, 350 g of toluene, and 202 g of triethylamine, start stirring to dissolve to obtain a light yellow transparent solution, and then place the reactor in an ice water bath at 0-10°C. The mixed solution of 181g of acryloyl chloride and 1g of p-hydroxyanisole was slowly dropped into the reaction kettle within 1.5h. After the mixed solution was dropped, the ice water bath was removed and the reaction kettle was placed in a warm water bath at 25°C continue the reaction for 4 hours to obtain a reaction product solution.Pour the reaction product solution into the washing kettle, add 400g of deionized water and stir for 10min and then let it stand for 1h to release the lower layer of wastewater, then add 200g of deionized water and stir for 10min and then stand for 1h to release the lower layer of wastewater, and finally add 200g of 10% mass fraction After stirring for 10 minutes, let it stand for 1 hour to release the lower layer of wastewater. Transfer the water-washed reaction product solution to the reaction kettle, add 0.2g of p-hydroxyanisole, control the temperature at 65°C, remove the water-carrying agent under reduced pressure, until the content of the water-carrying agent is less than 500ppm, and then filter to obtain dark yellow brown transparent 4-phenylbenzyl acrylate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With water; sodium formate; sodium carbonate at 100 - 105℃; for 1h; | 5; 6 Example 5: Add to 1000ml flask4-biphenylbenzyl chloride100g (HPLC purity 65.2%, equivalent to 0.322mol), 400g water, 8.8g (0.129mol) of sodium formate, heated to 100-105°C. Slowly add 89.6 g (0.169 mol) of 20% sodium carbonate solution dropwise, control the pH of the reaction solution to be 7-7.5, and keep the reaction for 1 hour after dripping. Add 300g of ethyl acetate, stir evenly, stand for layering, steam 7075g of water from the lower water layer and directly use it as a hydrolyzing agent and solvent into the next batch of hydrolysis reaction; the upper oil layer will drop to about 20 to crystallize and filter,After drying, 54.0g (0.293mol) of 4-biphenylmethanol product was obtained, and the yield was 91.0%(Calculated based on the content of 4-biphenylbenzyl chloride), HPLC purity 99.0%. |
52% | With water at 100℃; for 24h; | 1 Example 1 To a 3 L autoclave were added biphenyl (350 g, 2.27 mol), cuprous chloride (1.0 g, 0.01 mol), paraformaldehyde (90 g, 1.0 mol), 85% phosphoric acid (270 g), and concentrated hydrochloric acid (1050 g). ) Close the reaction system, the pressure inside the reactor is about 3 atm, slowly heat and stir to 120°C, react for 36 hours, check the reaction by HPLC, cool down to 30°C, stand, remove the lower aqueous layer, add to the reactor Water (1400 g) was stirred and warmed up, heated to 100° C., refluxed, reacted for 24 hours, then cooled down to room temperature and filtered to give a crude product, which was recrystallized from three-fold amount of toluene to obtain 217 g of a white solid, which was passed through conventional The structural confirmation method was confirmed to be 4-biphenylmethanol. The purity of the HPLC assay was 98% and the yield was 52%. |
With water In N,N-dimethyl-formamide at 80℃; for 20h; Sealed tube; | 1.2 synthesis of 4-biphenylmethanol hydrolysis reaction: collected intermediates, 1200L water and DMF 150kg into the reactor, sealed and stirred, heated to 80 ° C, control pressure 0.3Mpa, reaction 20h, cooling pressure, cooling to 0-20 ° C crystal, centrifuged crude;[0026] 3) Refining process: take the crude product 380kg, ethyl acetate 648kg and activated carbon 20kg added to the reaction dad, the temperature heated to 80 ° C stirring lh, heat filtration, the filtrate cooled to 5 ° C after stirring 2h Experience products, dried finished products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: biphenyl-4-yl methanol With sodium hydride In N,N-dimethyl-formamide; mineral oil at 90℃; for 3h; Inert atmosphere; Stage #2: 3,3-bis(bromomethyl)-3,4-dihydro-2H-thieno[3,4-b][1,4]dioxepine In N,N-dimethyl-formamide; mineral oil at 95℃; for 24h; Inert atmosphere; | Compound 4: To a nitrogen-degassed solution of 100 mL ofdimethyl formamide dissolved with 0.24 g of NaH (60% dispersionin mineral oil)in dried round-bottom flask, 0.68 g of 4-Hydroxymethylbiphenyl was added dropwise, followed by stirringof the mixture at 90 °C under nitrogen atmosphere for 3 h.Then 0.5 g of compound 1 was added and the reaction mixture wascontinued to react for another 24 h at 95 °C. After reaction, themixture was poured into 200 mL of saturated brine after cooling and extracted with anhydrous ether (100 mL) twice. The organicphase was dried over sodium sulfate, and the excessive solventswere removed through rotary evaporation. The gained crudeproduct was purified by silica column chromatography (petroleum)to afford colorless oil. 1H NMR (400 MHz, CDCl3, ppm): δ 7.54-7.62(m, 8H), 7.35-7.47 (m, 10H), 6.48 (s, 2H), 4.60 (s, 4H), 4.41 (s, 4H),3.68 (s, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With tetramethylammonium bromide; cesium fluoride In N,N,N,N,N,N-hexamethylphosphoric triamide; N,N-dimethyl acetamide at 70℃; for 26h; Inert atmosphere; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With potassium hydroxide In toluene at 110℃; for 4h; | |
78% | With carbonylhydrido(tetrahydroborato)[bis(2-diphenylphosphinoethyl)-amino]ruthenium(II); potassium hydroxide In toluene at 110℃; for 16h; Inert atmosphere; Sealed tube; Glovebox; | 4.1. General Procedures General procedure: Glovebox Procedure (General Procedure 1): Inside an argonfilled glovebox (O2 levels between 35.0 and 55.0 ppm, H2O levels unknown), to an oven dried 10-mL screw cap vial equipped with a Teflon-coated magnetic stir bar were added Ru-MACHO (1.2 mg, 2.00 mmol), KOH (1.7 mg, 30.0 mmol), and the appropriate phosphinic amide (0.200 mmol) in that order. Subsequently, toluene (0.7 mL) was added via micropipette, with care taken to ensure that solids on the wall were washed to the bottom of the vial. Next, the appropriate alcohol (0.240 mmol) was added either as a solid or via micropipette for liquid substrates. The reaction was sealed tightly with a non-puncturable cap and was further sealed by placing a piece of electrical tape around the cap and top of vial. Schlenk Line Procedure (General Procedure 2): To a flame-dried vial were quickly added Ru-MACHO (1.2 mg, 2.00 mmol) and KOH (1.7 mg, 30.0 mmol) (stored under Ar) (addition time 1 min), and the reaction vial was left open under a steady flow of nitrogen (applied via a needle placed at the top of the vial). Next, the appropriate phosphinic amide (0.200 mmol) was added, followed by the addition of toluene (0.7 mL) from a standard Solvent Purification System (SPS). Lastly, the appropriate alcohol (0.240 mmol) was added either as a solid or via micropipette for liquid substrates. The nitrogen line was removed, and the vial was then quickly and tightly sealed with a non-puncturable cap and further sealed by placing a piece of electrical tape around the cap and top of the vial. After the differing series of operations described above, General Procedures 1 and 2 then followed then same protocol. The reaction vessel was placed in a preheated oil bath at 110e140 C with a stirring rate of 500 rpm. As the reaction was proceeding, the vessel was periodically visually monitored. If large amounts of solid were found to have accumulated on the wall, the vial was briefly removed from the oil bath and shaken to wash the solids back to the bottom of the vial. After 16 h, the vial was removed from the oil bath and allowed to cool to room temperature. Methanol (1 mL) was added to dissolve all solids, and the solvent removed in vacuo. The solid was redissolved in methanol (1 mL), and the solution was filtered through a 40-mm syringe filter. Samples were then purified by reverse-phase HPLC or recrystallized from hot benzene. In the case of HPLC purification, the fractions were combined, frozen in liquid N2, and lyophilized to sublime the solvent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triphenylphosphine In tetrahydrofuran at 0 - 20℃; for 24.5h; Inert atmosphere; | 1.1.3. General procedure for the Mitsunobu synthesis of amines 1 General procedure: To a stirred solution of the tert-butyl 4-hydroxybenzylcarbamate (5.0 mmol) in dry THF under nitrogen atmosphere, the corresponding benzyl alcohol (5.0 mmol) and PPh3 (5.0 mmol) were added at 0°C. Afterwards, DIAD or DEAD (5.0 mmol) was added dropwise for over 10 min. The reaction mixture was stirred at 0°C for 20 min and then at rt for 24 h. The solvent was removed under reduced pressure and the product was purified by flash chromatography (petroleum ether/EtOAc 5:1) giving the corresponding amines 1q-ad. The procedures above were used in order to further use the compound as free amine or its trifluoroacetic/hydrochloric salt. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39% | With fluorosulfonyl fluoride; caesium carbonate at 20℃; for 12h; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | Stage #1: 2,3-Dihydroxybenzoic acid With dicyclohexyl-carbodiimide In acetonitrile at 50℃; for 1h; Stage #2: biphenyl-4-yl methanol With dmap In acetonitrile at 65℃; for 3h; | General esterification procedure for the synthesis of B1-B11 and C1-C4 General procedure: N, N-dicyclohexylcarbodiimide (1.55 g, 7.5 mmol) was added to a solution of 2,3-dihydroxybenzoic acid (0.77 g, 5.0 mmol) in anhydrous CH3CN (20 mL). The reaction mixtures were stirred for 1 h at 50 oC until complete dissolution of the solids was achieved. Next corresponding phenol or alchol (5 mmol) and DMAP (0.06 g, 0.5 mmol) were added to the mixtures and stirred for 3 h at 65 oC, then the mixtures were concentrated under reduce vacuum. The residue was extracted with ethyl acetate three times and then filtered. The filtrate was washed with 5% aqueous citric acid solution, saturated NaHCO3 and brine successively. The organic phase was dried over Na2SO4, filtered, and then concentrated. The crude mixture was purified by column chromatography on silica gel to afford B1-B11 and C1-C4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With tetrabutylammomium bromide; potassium acetate; palladium diacetate; tris-(o-tolyl)phosphine; In 1-methyl-pyrrolidin-2-one; at 110℃; for 4h;Schlenk technique; Inert atmosphere; | General procedure: Cross-coupling of 1a with Bi(p-tolyl) 3 : An oven-dried Schlenk tube was charged with (2-iodophenyl)methanol (1a) (0.75 mmol, 3 equiv.), Bi(p-tolyl) 3 (0.25 mmol, 1 equiv.), Pd(OAc) 2 (0.025 mmol, 0.1 equiv.), P(o-tolyl) 3 (0.1 mmol, 0.4 equiv.), KOAc(1.5 mmol, 6 equiv.), TBAB (0.75 mmol, 3 equiv.) and NMP (3 mL) under a N 2atmosphere. The mixture was stirred in an oil bath at 110 C for 4 h. The contents were quenched with water (10 mL) at rt and extracted with ethylacetate (30 mL). The organic extract was washed with brine and dried usingMgSO 4 . The organic solvent was removed under reduced pressure to obtain thecrude product. It was puried by silica gel chromatography using hexane/ethylacetate as eluent. The product 2a was obtained in 74% yield. The spectralcharacterization data for all the products is given in the Supporting information. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With trichloroisocyanuric acid; cesium fluoride In acetonitrile at 20℃; for 24h; Inert atmosphere; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With potassium <i>tert</i>-butylate In acetonitrile at 70℃; for 8h; | 2. General procedure for polyfluorinated aromatic ethers General procedure: Reaction conditions: To a 25 mL Shrek tube were sequentially added (thio)alcohol or (thio)phenol (0.2 mmol), B(C6F5)3 (35mol%, 35.8 mg), t-BuOK (0.2 mmol, 1.0 equiv, 22.4 mg) and CH3CN (2.0 mL). The formed mixture was stirred at 70 °C for 8h as monitored by TLC and GC-MS. After completion of the reaction, the crude product was concentrated and purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate) to afford the corresponding products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
133 mg | With sodium tetrahydridoborate In dichloromethane; N,N-dimethyl acetamide at 20℃; for 1h; |
Tags: 3597-91-9 synthesis path| 3597-91-9 SDS| 3597-91-9 COA| 3597-91-9 purity| 3597-91-9 application| 3597-91-9 NMR| 3597-91-9 COA| 3597-91-9 structure
[ 53076-11-2 ]
Bicyclo[4.2.0]octa-1,3,5-trien-3-ylmethanol
Similarity: 0.92
[ 53076-11-2 ]
Bicyclo[4.2.0]octa-1,3,5-trien-3-ylmethanol
Similarity: 0.92
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