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CAS No. : | 120-51-4 | MDL No. : | MFCD00003075 |
Formula : | C14H12O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | SESFRYSPDFLNCH-UHFFFAOYSA-N |
M.W : | 212.24 | Pubchem ID : | 2345 |
Synonyms : |
Phenylmethyl benzoate;Ascabiol;Benzoic acid benzyl ester;Scabitox;Novoscabin
|
Num. heavy atoms : | 16 |
Num. arom. heavy atoms : | 12 |
Fraction Csp3 : | 0.07 |
Num. rotatable bonds : | 4 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 62.21 |
TPSA : | 26.3 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) : | -4.78 cm/s |
Log Po/w (iLOGP) : | 2.68 |
Log Po/w (XLOGP3) : | 3.97 |
Log Po/w (WLOGP) : | 2.89 |
Log Po/w (MLOGP) : | 3.41 |
Log Po/w (SILICOS-IT) : | 3.29 |
Consensus Log Po/w : | 3.25 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.95 |
Solubility : | 0.0239 mg/ml ; 0.000113 mol/l |
Class : | Soluble |
Log S (Ali) : | -4.22 |
Solubility : | 0.0127 mg/ml ; 0.0000598 mol/l |
Class : | Moderately soluble |
Log S (SILICOS-IT) : | -5.01 |
Solubility : | 0.00205 mg/ml ; 0.00000966 mol/l |
Class : | Moderately soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 2.0 |
Synthetic accessibility : | 1.44 |
Signal Word: | Danger | Class: | 9 |
Precautionary Statements: | P201-P260-P263-P264-P270-P271-P273-P304+P340+P312-P308+P313-P391-P501 | UN#: | 3082 |
Hazard Statements: | H332-H362-H372-H411 | Packing Group: | Ⅲ |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With tert.-butylhydroperoxide; copper(l) chloride; In decane; tert-butyl alcohol; at 50℃; for 12h; | General procedure: To a test tube charged with CuCl (2.0 mg, 0.02 mmol) andisochroman (1a; 251 muL, 2.0 mmol) in t-BuOH (20 mL) wasadded TBHP (5.0-6.0 M in decane, 10.9 muL, 0.6 mmol) and themixture was stirred and heated at 50 C for 12 h under open air.After cooling to room temperature, the reaction was quenchedwith 25% aqueous ammonia solution and water then themixture was extracted with EtOAc. The separated organic layerwas dried over Na2SO4 and products were concentrated after filtration.The residue was purified by silica gel column chromatography(EtOAc/hexane, 1:10) to give isochromanone (2a) as acolorless oil in 83% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Produkt 5:Isobutylisobutyrat; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With [(ImDippN)Th{N(SiMe3)2}3] In hexadeuterobenzene at 20℃; for 24h; | |
99% | With lithium In hexane at 20℃; for 96h; concn. of title compd., reaction time varied; reaction at metal surface; | |
99% | With bis(cycloocta-1,5-diene)nickel(0); 4,5-dichloro-1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene In toluene at 23 - 60℃; Inert atmosphere; |
99% | With 1,2-dibenzyl diselenide; Di-n-butylmagnesium In tetrahydrofuran; n-heptane at 25℃; for 24h; Molecular sieve; Inert atmosphere; | |
99.2% | With C59H55AlN2O2 In neat (no solvent) for 6h; Inert atmosphere; Schlenk technique; | 5.9 General procedure for Tishchenko reaction catalyzed by aluminum alkoxide complexes General procedure: aldehyde (10mmol) was added to a 10mL Schlenk flask charged with 0.05mmol aluminum alkoxide complexes under nitrogen. Immediately, a yellow solution was obtained with stirring at room temperature. After the reaction was completed, it was diluted with HCl solution (0.5M), and the mixture was extracted 3 times with CH2Cl2. The combined organic layers were dried over MgSO4. Removal of all volatiles in vacuo, the crude product was purified by column chromatography on silica gel (Hexane-EtOAc). |
98% | In hexadeuterobenzene at 21℃; for 24h; | |
98% | With sodium hydride for 0.5h; Neat (no solvent); High speed ball milling; | |
98% | With [{(C2H5)2NC(NC6H11)2}ZnEt]2 In neat (no solvent) at 80℃; for 12h; Inert atmosphere; Schlenk technique; | |
98% | With C18BF16(1-)*C34H53F2NiOP2(1+) In toluene at 20℃; for 1h; Glovebox; Inert atmosphere; | |
97% | With 18-crown-6 ether; potasssium hydride In hexadeuterobenzene at 23℃; for 0.083h; Inert atmosphere; | |
97% | With [{(PhN)MeC(Nt-Bu)}AlMe(μ-OMe)]2 at 80℃; for 8h; Inert atmosphere; Schlenk technique; Green chemistry; | 2.5 General procedure employed for the Tishchenko reaction General procedure: The pre-catalyst, amidinatoaluminum compound (0.8 mmol) was placed in a dry Schlenk flask under a nitrogen atmosphere, and freshly distilled aldehyde (80 mmol) was introduced. The mixture was immediately stirred at room temperature for 30 min to produce the corresponding ester. The reaction was quenched with 0.5 ml of water and the product was distilled to collect the corresponding ester. The yields reported are the isolated yield. |
97% | With Aluminum Chloride; triethylamine In dichloromethane at 20℃; for 48h; | General experimental methods for AlCl3-catalyzedCannizzaro/Tishchenko reactions General procedure: A mixture of AlCl3(0.5 mmol), the aldehyde (10 mmol),and triethylamine (5 mmol) was added to 2 cm3of driedCH2Cl2and stirred for 2 days at room temperature underargon atmosphere until the aldehyde was completelyconsumed. The reaction progress was probed by TLCand GC/MS (Agilent 6890 (GC)/5972A (MS)). The reactionmixture was then filtered through Whatman filterpaper (grade 2), and treated with sodium bicarbonatesolution, followed by isolating the organic phase via aseparatory funnel. The aqueous phase washed severaltimes with CH2Cl2to make sure that all organic materialsextracted. Then, the organic phase was dried usingsodium sulfate and subsequently analyzed by GC/MSand 1H NMR, and validated using melting or boilingpoint of the product. |
96% | With triethylamine; lithium bromide at 20℃; for 48h; | |
96% | With phenylmethanethiol; phenyl magensium bromide In tetrahydrofuran; diethyl ether at 65℃; for 24h; Inert atmosphere; | |
96% | With Me2SiCp''2Th(n-C4H9) In hexadeuterobenzene at 25℃; for 24h; chemoselective reaction; | |
95% | With [tris(2,6-diphenylbenzyl)siloxy]dimethylaluminum In toluene at 21℃; for 5h; | |
95% | With sodium hydride In toluene at 23℃; for 18h; Inert atmosphere; | |
95% | With C31H49ErN2OSSi In toluene at 20℃; for 4h; Inert atmosphere; | |
93% | In hexadeuterobenzene at 20℃; for 0.75h; | |
92% | With biphenyl; natrium In hexane for 5h; other aromatic aldehydes, reaction without biphenyl.; | |
92% | With biphenyl; natrium In hexane for 5h; Heating; | |
92% | With di-μ-chlorobis-[(η6-p-cymene)chlororuthenium(II)]; anhydrous sodium formate; cyclohexyldiphenylphosphine In 1,4-dioxane at 80℃; for 20h; Inert atmosphere; | |
92% | With Mg[iPr2NC{N-2,6-Me2-C6H3}2]2 In neat (no solvent) at 25℃; for 21h; Inert atmosphere; | General procedure for the Tishchenko reaction General procedure: The required amount of catalyst and aldehyde both were placed in a dry sample vial with a stirring bar inside the glove box. Subsequently, sealed vial brought outside the glove box and stirred at room temperature or heated to 80°C till completion of the reaction. The reaction was monitored by thin layer chromatography (TLC) and aliquot of reaction mixture by NMR spectroscopy. Final product was purified by column chromatography (Hexane/diethyl ether (98:2)) |
91% | With [3-(dimethylamino)propyl]dimethyl aluminium(III) In n-Pentane at 80℃; for 5h; | |
91% | With 2C9H15N2(1-)*Na(1+)*2CH3(1-)*Al(3+) In neat (no solvent) at 50℃; for 3h; Schlenk technique; Inert atmosphere; | 2.3. General procedure for Tishchenko reaction with sodium organoaluminate complex as catalyst General procedure: Benzaldehyde (102 uL, 10 mmol) was added to a 25 mL Schlenk tube charged with sodium organoaluminate (0.076 g, 0.2 mmol) under nitrogen. After the reaction mixture was stirred for 3 h at 50 °C, it was quenched with HCl solution (0.5 M), and was ex- tracted three times with ethyl acetate. The combined organic lay- ers were dried over Na 2 SO 4 . Removal of all volatiles in vacuo, the crude product was purified by column chromatography on sil- ica gel (Hexane/EtOAc: 10/1-5/1). All carbonates were identified through comparisons with the NMR data reported in the literatures [2o]. |
90% | With 4-tert-butylbenzyl mercaptan; phenyl magensium bromide In tetrahydrofuran; diethyl ether at 110℃; for 0.5h; Microwave irradiation; Inert atmosphere; | |
88.6% | With [{2-(CH3NCH2)C4H3N}Li2(TMEDA)3] In neat (no solvent) at 70℃; for 3h; Inert atmosphere; Schlenk technique; | General procedure for the Tishchenko reaction catalyzed by 2-aminopyrrolyl dilithium compound General procedure: Benzaldehyde (25 mmol) was added to a 15 mL Schlenk flask charged with 5.4 mg (0.5 mmol) of 2-aminopyrrolyl dilithium compound under nitrogen. Immediately, a yellow solution was obtained with stirring at r.t. After the reaction mixture was stirred for 3 h at 70 °C, it was diluted with HCl solution (0.5 M), and the mixture was extracted 3 times with CH2Cl2. The combined organic layers were dried over MgSO4. Removal of all volatiles in vacuo, the crude product was purified by column chromatography on silica gel (Hexane-EtOAc). |
87% | With tris[N,N-bis(trimethylsilyl)amide]lanthanum In hexadeuterobenzene at 21℃; | |
86% | With potassium carbonate In acetonitrile at 20℃; for 12h; | |
85% | In hexadeuterobenzene at 20℃; for 48h; | |
85% | In tetrahydrofuran at 20℃; for 168h; Schlenk technique; Inert atmosphere; | |
81% | With Rh(PhBP3)(H)2(NCMe); hydrogen In toluene at 20℃; for 0.166667h; | |
76% | With (pentamethylcyclopentadienyl)2NdCH(TMS)2 In benzene Ambient temperature; | |
76% | With tris(methyl)aluminum; 2,7-dimethyl-1,8-biphenylenediol; benzylic alcohol In hexane; toluene at 21℃; for 5h; | |
74% | With calcium bis{bis(trimethylsilyl)amide} In benzene at 20℃; for 24h; | |
70% | With sodium methoxide In tetrahydrofuran at 25℃; for 16h; | |
68% | In toluene at 20℃; for 5h; | |
68% | With tris(N-2',6'-diisopropylphenyl(naphthyl)amidate)yttrium mono(tetrahydrofurane) In toluene at 20℃; for 1h; Inert atmosphere; | |
67% | With (2,7-dimethyl-1,8-biphenylenedioxy)bis(dibenzyloxyaluminum) In toluene at 21℃; for 5h; | |
60% | With Mg(Ph2PC{NCy}2)(N{SiMe3}2)(THF); 1,4-dimethoxybezene In hexadeuterobenzene at 20℃; for 0.5h; Inert atmosphere; Schlenk technique; Glovebox; | |
58% | With tris(methyl)aluminum; benzene-1,2-diol; isopropanol In dichloromethane at 20℃; for 23h; | |
56% | With bis[chlorido(η2,η2-cycloocta-1,5-diene)rhodium(I)]; Cs2CO3; ortho-nitrofluorobenzene In toluene at 115℃; for 20h; Schlenk technique; Sealed tube; | |
52% | In (2)H8-toluene at 120℃; for 24h; Inert atmosphere; Sealed tube; | |
40% | With 2,4,6-trimethyl-pyridine; hydrogen In toluene at 55℃; for 4h; | |
37% | With C12H30LiO6(1+)*C46H68N8Si4Yb(1-) In tetrahydrofuran at 25℃; for 3h; Inert atmosphere; | |
at 300 - 320℃; im Rohr; | ||
With Rh(PPh3)4 In benzene at 50℃; for 0.00833333h; var. times, temp.; | ||
With lithium hydride; Petroleum ether at 200℃; | ||
With sodium hydride; benzene at 80℃; | ||
With iodine; magnesium; toluene | ||
With ethanol; magnesium aluminium-ethylate | ||
at 300 - 320℃; 15-stdg. Erhitzen; | ||
With diethyl ether; natrium | ||
With ethynylmagnesium bromide | ||
With iodine bei der Belichtung im Rohr; | ||
With aluminum tri-ethoxide | ||
at 350 - 370℃; 2-stdg. Erhitzen; | ||
Reaktion ueber mehrere Stufen; | ||
With n-butylmagnesium iodide | ||
94 % Chromat. | With Cp82La(CH(SiMe3)2 In benzene for 72h; Ambient temperature; | |
85 % Chromat. | In hexane; toluene at 20℃; for 24h; | |
100 % Spectr. | In hexadeuterobenzene at 21℃; | |
Multi-step reaction with 2 steps 1: tolane, water / Ru3(CO)12 / 13 h / 147 °C 2: 72 percent / tolane / Ru3(CO)12 / 2 h / 147 °C | ||
Multi-step reaction with 2 steps 1: tolane, water / Ru3(CO)12 / 13 h / 147 °C 2: 80 percent / tolane / Ru3(CO)12 / 2 h / 147 °C | ||
Multi-step reaction with 2 steps 1: sodium; diethyl ether / und Zersetzen des Reaktionsprodukts mit eiskalter verduennter Essigsaeure 2: potassium cyanide / 160 °C / im Rohr | ||
In hexadeuterobenzene at 20℃; | ||
With C26H60Mg2N8Si4 In hexadeuterobenzene Inert atmosphere; | ||
With Mg(mesC{NCy}2)(N{SiMe3}2)(THF) for 24h; Inert atmosphere; | ||
With calcium carbide; di-i-propyl amine In N,N-dimethyl-formamide | ||
60 %Spectr. | With C48H69N3Th In hexadeuterobenzene at 20℃; for 24h; Glovebox; Inert atmosphere; | |
Multi-step reaction with 2 steps 1: trichloroisocyanuric acid / dichloromethane / 120 h / 20 °C / Inert atmosphere 2: triethylamine; dmap / dichloromethane / 1 h / 0 - 20 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1: C25H27BF3N7NiO; hydrogen / tetrahydrofuran / 72 h / 120 °C / 9293.22 Torr / Glovebox 2: C25H27BF3N7NiO / toluene / 24 h / Glovebox; Schlenk technique; Reflux; Inert atmosphere | ||
Multi-step reaction with 2 steps 1: trans-[(2-(diphenylphosphanyl)-N-(pyridine-2-ylmethyl)ethaneamine)RuCl2(PPh3)]*dichloromethane; potassium-t-butoxide; hydrogen / isopropanol / 0.33 h / 60 °C / 7500.75 Torr / Inert atmosphere; Autoclave 2: trans-[(2-(diphenylphosphanyl)-N-(pyridine-2-ylmethyl)ethaneamine)RuCl2(PPh3)]*dichloromethane; potassium-t-butoxide / toluene / 8 h / Inert atmosphere; Schlenk technique; Reflux | ||
100 %Spectr. | With [N{(C3F7)C(Dipp)N}2]ZnEt In neat liquid at 140℃; for 3h; Inert atmosphere; Schlenk technique; Glovebox; | |
Multi-step reaction with 2 steps 1: hydrazine / ethanol 2: manganese(IV) oxide; potassium dihydrogen orthophosphate / dichloromethane | ||
With [OsH2(CO){PyCH2NHCH2CH2NHPtBu2}] In toluene at 20℃; for 0.833333h; Inert atmosphere; | ||
With C36H32Cl2N2O2P2Ru; sodium hydroxide In toluene at 150℃; Inert atmosphere; Schlenk technique; | ||
With C38H53N3Th In hexadeuterobenzene at 20℃; for 24h; Glovebox; | ||
89 %Spectr. | With C39H80N6Si6Th In hexadeuterobenzene at 20℃; for 36h; Sealed tube; | 2.12 General procedure for the Tishchenko reactions General procedure: A J. Young Teflon sealed NMR tube was loaded with a certain amount of the precatalyst from a stock solution in C6D6. Then the respective aldehyde (100 equivalents) was added and immediately diluted to a total volume of 600μL with C6D6. The tube was sealed and taken out of the glovebox; the reaction progress was monitored by 1H NMR. The ratio between the ester products and aldehyde was calculated by integration of the methylene signals and aldehyde signals. Then the tube was opened to the air, and the reaction was quenched with methanol and submitted to MS analysis. The 1H NMR of ester products from homocoupling of benzaldehyde [28], 4-trifluromethylbenzaldehyde [58], 4-methylbenzaldehyde [26], 4-methoxylbenzaldehyde [27], 1-naphthaldehyde [28], 2-pyridinylaldehyde [28], 2-thiophencarboxaldehyde [28], fufural [28], isobutyraldehyde [28], cyclohexylaldehyde [28], 4-nitrobenzaldehyde [28], 3-nitrobenzaldehyde [27], 4-cyanobenzaldehyde [27], 2-naphthaldehyde [28], phthaldehyde [28], were compared with previous reports. |
Multi-step reaction with 2 steps 1: tri-n-octylmethylammonium chloride; tert.-butylhydroperoxide / chlorobenzene / 2 h / 40 °C 2: Cs2CO3 / N,N-dimethyl-formamide / 12 h / 20 °C | ||
Multi-step reaction with 2 steps 1: 1,3-dibromo-1,3,5-triazinane-2,4,6-trione / dichloromethane / 5 h / 20 °C 2: N-ethyl-N,N-diisopropylamine; dmap / dichloromethane / 0.33 h / 20 °C | ||
84 %Spectr. | With potassium-t-butoxide In hexadeuterobenzene at 20℃; for 24h; Glovebox; Inert atmosphere; Sealed tube; | |
Multi-step reaction with 2 steps 1: C24H30Cl2NPRuS2; potassium-t-butoxide; hydrogen / toluene; dichloromethane / 5 h / 80 °C / 15001.5 Torr / Autoclave 2: RuCl2(PPh3)[(EtSC2H4)2NH]; potassium-t-butoxide / toluene / 24 h / 110 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1: C24H30Cl2NPRuS2; potassium-t-butoxide; hydrogen / toluene; dichloromethane / 5 h / 80 °C / 15001.5 Torr / Autoclave 2: RuCl2(PPh3)[(EtSC2H4)2NH]; potassium-t-butoxide / toluene / 24 h / 110 °C / Inert atmosphere | ||
With tributylphosphine; copper; sodium hydride In tetrahydrofuran at 20℃; for 0.333333h; | ||
With pentacarbonyl(methyl)manganese(I); C21H38OP2 In (2)H8-toluene at 120℃; for 48h; Inert atmosphere; | ||
Multi-step reaction with 2 steps 1: trichloroisocyanuric acid / dichloromethane / 4 h / 20 °C / Inert atmosphere; Irradiation 2: dmap; triethylamine / dichloromethane / 1 h / 0 - 20 °C / Inert atmosphere | ||
99 %Spectr. | With C24H36AlN2O2(1+)*C24H12BCl8(1-) In neat (no solvent) at 18℃; Inert atmosphere; Schlenk technique; Glovebox; | |
With C80H79MgN3Si2 In hexadeuterobenzene at 25℃; Inert atmosphere; Schlenk technique; Glovebox; | ||
Multi-step reaction with 2 steps 1: N-chloro-succinimide; thio-xanthene-9-one / acetonitrile / 7 h / 20 °C / Irradiation 2: dmap / tetrahydrofuran / 16 h / Reflux |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With cyanomethylenetributyl-phosphorane In benzene at 100℃; for 24h; | |
100% | With TiO(acac)2 In xylene for 15h; Heating; | |
99% | With fluorosulfonyl fluoride; N-ethyl-N,N-diisopropylamine In 1,2-dichloro-ethane at 20℃; for 5h; | Esterification; General Procedure General procedure: Carboxylic acid 1 (1.0 mmol, 1.0 equiv), alcohol 2 (2.0 mmol, 2.0 equiv), DIPEA (3.0 mmol, 3.0 equiv) and DCE (the reaction mixture was diluted to 0.2 M) were added to an oven-dried 25 mL reaction flask equipped with a stir bar and sealed with a rubber stopper. SO2F2 gas was introduced into the stirred reaction mixture by slowly bubbling from a balloon [the balloons were made from low-density polyethylene (LDPE) which it not reactive with SO2F2]. The reaction mixture was stirred at room temperature for 5 h. After the reaction was completed, the reaction mixture was directly concentrated under vacuum and was purified by column chromatography on silica gel using a mixture of petroleum ether and ethyl acetate as eluent to give the desired product 3. To confirm the amount of SO2F2 consumed in this transformation, 4-biphenylcarboxylic acid (1a) (10 mmol, 1.0 equiv), EtOH (2a) (20 mmol, 2.0 equiv), DIPEA (30 mmol, 3 equiv) and DCE (the reaction mixture was diluted to 0.2 M) were added to an oven-dried 100 mL reaction flask equipped with a stir bar and sealed with a rubber stopper. A balloon filled with SO2F2 gas was weighed before introduction of the SO2F2 gas into the stirring reaction mixture by slow bubbling at room temperature. After the reaction complete, the SO2F2 balloon was weighed again to measure the difference in weight. It was calculated that the SO2F2 consumption was about 3.26 g (31.9 mmol, 3.2 equiv) in this particular reaction (some of the gas dissolved in the DCE solvent can be considered as unreacted but consumed). The corresponding ester product 3a was obtained in 98% yield after work-up. |
98.97% | With SiO2-SO3H 7%-w/w at 69℃; for 0.0833333h; Microwave irradiation; | Synthesis of benzyl benzoate a) H2SO4 catalyst: In this reaction, the amount of H2SO4 was adjusted so that the total H+ content (as a monoprotic acid) corresponded to the protons in SiO2-SO3H 20%-w/w catalyst/alcohol; the required standard quantities were scaled up 100-fold. Benzoic acid (68.39 g-0.56 mol), benzyl alcohol (10.81 g-0.10 mol) and 0.080 g of concentrated H2SO4 (7.8 × 10-4 mol) were irradiated for 5 min, with a final temperature of 110 °C. The reaction vessel was cooled to room temperature, and the total mixture analyzed by CG/MS, which evidenced total conversion of the alcohol to benzylbenzoate. b) SiO2-SO3H catalyst: in the reaction flask it was added 0.0076 g of the SiO2-SO3H (7%-w/w) and the standard quantities of both reagents. After 5 min of irradiation the temperature of the reaction rose to 70 °C. The vessel was cooled to room temperature, 30 ml of diethyl ether was added, and the mixture filtered. The organic extract was washed with 10.0 mL of saturated NaHCO3, dried over anhydrous MgSO4 and concentrated under reduced pressure. The residue was purified by chromatographic column using hexane and ethyl acetate as eluent to obtain the pure benzyl benzoate as colorless oil. Yield. 0.2080 g and 98.97%. The filtered catalyst was washed with 10 mL diethyl ether, and dried at 150 °C for 2 h before reuse. |
97% | In toluene at 115℃; for 7h; Heating / reflux; | 9.5 To 2.5 ml of the solution containing 5 mmol of carboxylic acid and 5 mmol alcohol, and containing 1 mol% of zirconium(IV) isoproxide (Zr(Oi-Pr)4) and 1 mol% of metallic isoproxide (M(Oi-Pr)3), 1 ml of N-butylpyridinium trifluoromethane sulfonate imide (ionic liquid) was added, and the mixture was brought to azeortopic dehydration by heating to reflux (bath temperature: 115°C) for predetermined length of time. The reaction solution was cooled to room temperature, hexan (8 ml)/ether (2 ml) was added thereto, the solution was stirred for 30 min and left still for another 30 min, and the organic layer was separated therefrom. Extraction with hexane/ether was repeated until there was no starting material and product remaining in the ionic liquid layer (confirmed by TLC). On the other hand, the remained ionic liquid layer per se was used for the following reaction. Meanwhile, in test 4, 100 mmol of carboxylic acid and 100 mmol of alcohol were used, 0.1 mol% of zirconium(IV) isoproxide (Zr(Oi-Pr)4) and 0.1 mol% of iron(III) isopropoxide (Fe(Oi-Pr)3) were used, 10 ml of the solvent was used, and 2 ml of N-butylpyridinium trifluoromethane sulfonate imide was used. The result is shown in Table 6. Table 6 Test Carboxylic Acid + AlcoholMetallilc Isopropoxide (M(Oi-Pr)3) Solvent Reaction Time (h) Ester Yield with Last Extraction (%) [Number of Attempts to Reuse the Catalyst] 1 4-phenylbutyric acid + benzyl alcohol Fe(III) heptane: 8 99 (15) 2 4-phenylbutyric acid + benzyl alcohol Ga(III) heptane: 8 98 (3) 3 4-phenylbutyric acid + benzyl alcohol Fe(III) octane: 12 99 (2) 4 4-phenylbutyric acid + cyclododecanol Fe(III) octane: 12 >99(3) 5PhCo2H + benzyl alcohol Fe(III) toluene: 7 97 (3) The zirconium(IV)-iron(III) catalyst could be recycled repeatedly as a solution of N-butylpyridinium trifluoromethane sulfonate imide without being isolated (tests 1 and 3 to 5). For example, in test 1, zirconium(IV)-iron(III) catalyst (1mol%) could be reused 15 times or more in esterification reaction of 4-phenylbutyric acid and benzyl alcohol in a biphasic solvent consisting of hepetane and N-butylpyridinium trifluoromethane sulfonate imide, without losing its activity at all. Likewise, zirconium(IV)-gallium(III) catalyst could also be reused as a solution of N-butylpyridinium trifluoromethane sulfonate imide (test 2). |
96% | With dmap; methanesulfonic acid; triethylamine 1.) THF, 1 h, 2.) -5 deg C, 7 h; | |
95% | Stage #1: benzoic acid With N-chlorobenzotriazole; triphenylphosphine In dichloromethane for 0.25h; Cooling; Stage #2: benzyl alcohol With triethylamine In dichloromethane at 20℃; for 0.666667h; | Preparation of benzyl benzoate by using PPh3/NCBT General procedure: To a cold solution of PPh3 (0.327 g, 1.25 mmol) in CH2Cl2 (3 mL), freshly prepared NCBT (0.194 g,1.25 mmol) was added with continuous stirring. Benzoic acid (0.122 g, 1 mmol) was then added and stirring was continued for 15 min. Benzyl alcohol (0.270 g, 2.5 mmol) was added and the temperature was raised up to room temperature. The pale yellow solution was neutralized by triethylamine (0.175 mL). Stirring was continued for 40 min at room temperature. The progress of the reaction was followed by TLC. Upon completion of the reaction, the concentrated residue was passed through a short silica-gel column using n-hexane-ethyl acetate (8:1) as eluent. Benzyl benzoate was obtained with 95% yield after removing the solvent under reduced pressure. |
94% | With dmap; picryl fluoride In acetonitrile for 3h; Ambient temperature; | |
93% | With triethylamine In dichloromethane 1.) 0 deg C; 2.)to rt and 1 h; with or without triethylamine or with collidine, less molar equiv. of QS-t; | |
93% | With triethylamine In dichloromethane 1.) 0 deg C; 2.) to room temperature and 1 h; | |
92% | In toluene for 15h; Heating; | |
92% | With molecualar sevies 4A In toluene at 120℃; for 15h; | 3.15 Example 3 [Scope of Substrate Application] By combining diversely the carboxylic acid of various structure and alcohol, the scope of substrate application of the tetravalent hafnium compound was examined. A Soxhlet tube filled with dried molecular sieves 4A (about 1.5 g) was connected to the top of a 5 ml eggplant flask contained with a teflon coated magnetic stirrer, and a cooling tube was further attached over said Soxhlet tube. Unless there is a particular point of concern, toluene solvent (2 ml) and 0.1 mol %, 0.2 mol % or 1 mol % of hafnium chloride (IV)•(THF)2 were added to carboxylic acid (10 mmol) and alcohol (10 mmol), and heating reflux was conducted in the argon for several hours at 120°C. After the reaction, the mixture solution was purified by direct silica gel column chromatography (eluant hexane:ethyl acetate=4:1 to 8:1), and the solution was dried under reduced pressure. The results are shown in Table 2. In Table 2, the following are shown: for the experiment of Entry 3, toluene solvent (5 ml) was used; for the experiment of Entry 4, 4-phenyl butanoic acid (36 mmol) and toluene solvent (4 ml) were used; for the experiment of Entry 5, the numerical value of yield showed in parenthesis is the value in the case the inventors wanted to use the catalyst; for the experiment of Entry 9, o-xylene solvent (2 ml) was used; for the experiment of Entry 14, enantiomer of carboxylic acid was used and at a yield of 84%, the enantiomer of ester was obtained; for the experiment of Entry of 17, 1,3,5-mesitylene solvent(2 ml) was used; for the experiments of Entry 18 and 19, the lactone value is shown for the yield. [TABLE-US-00002] TABLE 2 [CHEMMOL-00003] HfCl4.(THF)2 reaction entryRCO2H ROH (1 mol %) time (h) yield (%) 1 [CHEMMOL-00004] [CHEMMOL-00005] 0.2 6 97 2 [CHEMMOL-00006] [CHEMMOL-00007] 0.2 24 92 3 [CHEMMOL-00008] [CHEMMOL-00009] 0.1 18 >99 4 [CHEMMOL-00010] EtC(CH2OH)3 0.2 24 >99 5 [CHEMMOL-00011] [CHEMMOL-00012] 0.2 5 94 (36) 6 [CHEMMOL-00013] l-menthol 0.2 36 >99 7 [CHEMMOL-00014] [CHEMMOL-00015] 0.2 13 >99 8 [CHEMMOL-00016] Et3COH 1.0 24 0 9 [CHEMMOL-00017] PhOH 0.2 36 91 10 [CHEMMOL-00018] [CHEMMOL-00019] 0.2 10 92 11 [CHEMMOL-00020] [CHEMMOL-00021] 0.1 18 98 12 [CHEMMOL-00022] [CHEMMOL-00023] 0.2 7 96 13Et2CHCO2H [CHEMMOL-00024] 0.2 60 98 14 [CHEMMOL-00025] [CHEMMOL-00026] 0.2 13 98 15PhCO2H [CHEMMOL-00027] 0.2 15 92 16 [CHEMMOL-00028] [CHEMMOL-00029] 0.2 10 92 17PhCO2H3,5-Me2C5H3OH 1.0 24 95 18 [CHEMMOL-00030] 0.2 10 98 19 [CHEMMOL-00031] 0.2 10 94 [0022] As it is also shown in Table 2, every carboxylic acid reacted with primary and secondary alcohol, under the presence of the catalyst of 0.2 mol % and under, and produced ester quantitatively, but as it is shown from the experiment of Entry 8, it did not react with tertiary alcohol. Furthermore, as it is shown from the experiment of Entry 17, the aromatic substrates (benzoic acid and phenol) showed lower reactivity compared to aliphatic substrates, and when carboxylic acid and alcohol are both aromatics, the ester could be obtained at a high yield, by increasing the catalyst amount up to 1 mol %. Moreover, when the reactivity is low, it is also effective to use a benzene solvent of higher boiling point, for example, o-xylene of the experiment of Entry 9 or 1,3,5-mesitylene of the experiment of Entry 17 and to conduct heating reflux. |
92% | Stage #1: benzoic acid With 2,2,4,4,6,6-hexachloro-1,3,5-triaza-2,4,6-triphosphorine In neat (no solvent) at 20℃; for 0.0166667h; Stage #2: benzyl alcohol In neat (no solvent) at 20℃; for 0.0833333h; | Generalprocedure for the preparation of esters 3a-n General procedure: A mixture of carboxylic acid (1 mmol) and TAPC (0.5 mmol, 0.17 g) was prepared in a mortar. The mixturewas ground with a pestle for 1 min. Then alcohol (1 mmol) was added to thereaction mixture and grinding was continued at room temperature for appropriatereaction times indicated in Table 1. After completion of the reaction(monitored by TLC), H2O (10 mL) was added to the reaction mixture.The residue was then extracted with EtOAc (4 × 5 mL), and the combined extractswere dried over MgSO4. The filtrate was evaporated, and the esterwas obtained as the only product. |
91% | With 1H-imidazole; iodine; chloro-diphenylphosphine In acetonitrile for 4h; Reflux; | |
91% | With 2-butyl-1,3-diphenyl-1,3,2-diazaphospholidine; 1,1'-azodicarbonyl-dipiperidine In 1,2-dichloro-ethane at 40℃; | |
90% | With di(n-butyl)tin oxide | |
90% | With silphos at 20℃; for 0.166667h; Neat (no solvent); | |
90% | With C26H32N4O6S2(2+)*2HO4S(1-) at 79.84℃; for 1.5h; Neat (no solvent); | |
90% | With dmap; triethylamine; trichlorophosphate In dichloromethane at 20℃; for 2h; | |
90.6% | With 1-(tert-butyl)-2-(chlorobenzyl) azodicarboxylate; triphenylphosphine In dichloromethane at 0 - 20℃; for 3h; | General procedure for Mitsunobu reactions General procedure: A solution of azo-reagent (1.2 mmol) in THF or CH2Cl2 (3 mL) was added slowly to the solution of alcohol (1 mmol), acidic pronucleophile (1.2 mmol) and Ph3P (1.2 mmol) in THF or CH2Cl2 (5 mL) at 0-5 °C and the reaction mixture was continued stirring a troom temperature. The reaction was monitored by TLC. The solution was concentrated and the toluene was added. The 1-(tert-butyl)2- (4-chlorobenzyl) hydrazinedicarboxylate (4a) precipitated and was filtered off. Then the filtrate was evaporated under reduced pressure. The product was purified by column chromatography on silica gel to afford the pure products. |
89% | With pyrographite; toluene-4-sulfonic acid for 0.00972222h; Microwave irradiation (675 W); | |
89% | With ytterbium perfluorooctanesulfonate Amberlyst A-21 supported In toluene at 100℃; for 12h; | |
89% | With 5,5'-dimethyl-3,3′-azoisooxazole; triphenylphosphine In acetonitrile for 6.5h; Reflux; | |
89% | In neat (no solvent) at 80℃; for 3.5h; | General procedure: General procedure: An organic acid (1 g), alcohol (excess) and catalyst (0.1 g) mixture was heated in a round bottomed flask. The completion of reaction is indicated by the total disappearance of acid. Then after, the catalyst was separated by filtration and reused. Sodium bicarbonate solution was added to the filtrate and removed with ether. With anhydrous sodium sulphate, the extract was dried and solvent was removed. Using ethyl acetate and petroleum ether, the pure product was isolated by column chromatography. |
89% | With 18-crown-6 ether; 2-(trimethylsilyl)phenyl trifluoromethanesulfonate; cesium fluoride In acetonitrile at 70℃; for 8h; | |
88% | With diazene-1,2-diylbis(morpholinomethanone); tributylphosphine In tetrahydrofuran at 20℃; for 16h; Inert atmosphere; | Typical procedure: General procedure: A solution of phenol (47 mg, 0.5 mmol, 1 equiv), benzylalcohol (108 ll, 1.0 mmol, 2 equiv) and PBu3 (250 ll, 1.0 mmol, 2 equiv) inanhydrous THF (7 mL) was stirred at RT for 2 min. ADDM (256 mg, 1.0 mmol,2 equiv) was added in one portion. The reaction mixture was stirred at RT for16 h under an inert atmosphere. The solvent was concentrated under reducedpressure, and then the residue was adsorbed onto silica gel from CH2Cl2, andpurified by flash column chromatography (eluent: Hex/EtOAc, 9:1) |
88% | Stage #1: benzoic acid With 2,4,6-trichlorobenzoyl-N',N'-dimethyl-4-aminopyridinium chloride; N-ethyl-N,N-diisopropylamine In toluene for 0.0166667h; Stage #2: benzyl alcohol In toluene at 20℃; for 24h; | General Procedure for the Synthesis of Esters To a solution of benzoic acid (0.20 mmol) and DIPEA (0.26 mmol) in 2 mL of anhydrous toluene was added TCB-DMAP (1) (0.26 mmol) and stirred for 1 min. The mixture was added Benzyl alcohol (0.20 mmol) over 1 min and stirred for 24 h at room temperature. The residue was dissolved in EtOAc (20 mL), and the solution was washed with H2O (15 mL x 2), sat. NaHCO3 (15 mL x 2),H2O (15 mL x 2), 1 M HCl (15 mL x 2) and brine (15 mL x 2). The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by chromatography (Hex : EtOAc, 100 : 1) to give benzyl benzoate (88% yield).1H NMR (500 MHz, CDCl3) δ 5.37 (s, 2H), 7.40 (m, 7H), 7.55 (m, 1H), 8.07 (m, 2H); 13C NMR (500 MHz, CDCl3) δ 166.6, 136.2, 133.2, 130.2, 129.8, 128.7, 128.5, 128.4, 128.3, 66.8; IR (neat, KBr , cm-1) 1720; HRMS [M]+ calcd for C14H12O2 212.0837, found 212.0838 |
86% | With diphenylphosphinopolystyrene; diethylazodicarboxylate In tetrahydrofuran at 25℃; for 4h; | |
86% | With pyridine for 0.5h; Ambient temperature; | |
86% | With triphenylphosphine In acetonitrile for 3h; Heating; | |
86% | With montmorillonite KSF for 0.00555556h; Microwave irradiation; Green chemistry; | |
85% | With dmap; S=P(Cl)(2-benzoxazolinone-3-yl)2; triethylamine In dichloromethane for 3h; Ambient temperature; | |
85% | With [1-(3-sulfonic acid)]propyl-3-methylimidazolium hydrogen sulfate at 95℃; for 4h; | |
85% | Stage #1: benzoic acid With (E)-ethyl 2-cyano-2-(2-nitrophenylsulfonyloxyimino)acetate; N-ethyl-N,N-diisopropylamine In dichloromethane at 25℃; Stage #2: benzyl alcohol In dichloromethane at 25℃; | |
82% | Stage #1: benzoic acid With (chloro-phenylthio-methylene)dimethylammonium chloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.5h; Stage #2: benzyl alcohol In dichloromethane at 20℃; for 12h; | |
81% | With oxone at 65℃; for 40h; | 4.2 General procedure for preparation of esters (RCO2R′) 5 from acids (RCO2H) 1 General procedure: A mixture of acid 1 (0.5mmol), oxone (0.15mmol) and alcohol (1.5mL) in round bottomed flask was stirred at 65°C. After completion of the reaction that was confirmed by thin layer chromatography the crude mixture was cooled to room temperature, filtered and purified by column chromatography using silica gel (100-200 ) with ethyl acetate and hexane as an eluent to afford the desired product 5 in 70-99 % yields. |
78% | Stage #1: benzoic acid With pyridine; N,N'-carbonyldisaccharin In 1-methyl-pyrrolidin-2-one at 50 - 60℃; for 1h; Stage #2: benzyl alcohol With triethylamine In 1-methyl-pyrrolidin-2-one at 50 - 60℃; for 48h; | |
77% | With isocyanate de chlorosulfonyle; triethylamine In dichloromethane 1.) 0 - 10 deg C, 3 h, 2.) room temp., 8 h; | |
75% | With PPh3-containing polystyrene non-cross-linked polymer; diethylazodicarboxylate In tetrahydrofuran at 20℃; for 0.5h; | |
75% | With 2,6-dimethylpyridine; 2-chloro-1-methyl-pyridinium iodide at 60℃; for 16h; Inert atmosphere; Green chemistry; | |
73% | With cerium(IV) trifluoromethanesulfonate In tetrachloromethane for 20h; Heating; | |
72% | With silica gel; zinc trifluoromethanesulfonate for 0.0666667h; microwave irradiation; | |
69% | With aluminium trichloride; sodium iodide In acetonitrile for 1h; Heating; | |
65% | With methyl azodicarboxylate polystyrene resin 3a; triphenylphosphine In tetrahydrofuran at 25℃; | |
57% | With C22H25F3N3O2(1+)*Cl(1-); oxygen; triphenylphosphine In acetonitrile at 50℃; for 48h; Molecular sieve; | |
50% | With dmap; N,N’-diisopropylbenziodazole; triphenylphosphine In chloroform for 24h; Reflux; | General procedure for oxidatively assisted coupling reactions of carboxylic acids with alcohols or amine General procedure: A mixture of 7a (67 mg, 0.180 mmol) and DMAP (22 mg, 0.180 mmol) in CHCl3 (5.0 mL) was stirred at reflux for 1 h. Then, carboxylic acid 9 (0.210 mmol), PPh3 (39 mg, 0.150 mmol) and alcohol 10 (0.150 mmol) or amine 12 (0.150 mmol) were added to the solution. The reaction mixture was stirred at reflux for 24 h. After reaction, saturated aqueous NaHCO3 (5 mL) was added and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by preparative TLC (hexane/ethyl acetate = 1:1) afforded the analytically pure 11 or 13. |
47% | With cobalt(II) chloride In acetonitrile at 80℃; for 14h; | |
47% | With dichloro(dimethylglyoxime)(dimethylglyoximato)cobalt(III); [4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridine-N1,N1′]bis{3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-κN]phenyl-κC}iridium(III) hexafluorophosphate; caesium carbonate; triphenylphosphine In dichloromethane at 20℃; Inert atmosphere; Sealed tube; Irradiation; | |
20% | With di-tert-butyl peroxide; [HSItBu][FeBr4] at 110℃; for 24h; | |
With tin at 200℃; | ||
With S,S-bis<4,6-dimethyl-2-pyrimidinyl> dithiocarbonate; copper(ll) bromide 1.) CH3CN, room temp., 1 h; 2.) room temp., 7 h; Yield given. Multistep reaction; | ||
With fluorosulfonylchloride; triethylamine 1.) 1 h, r.t., 2.) 2 h; Yield given. Multistep reaction; | ||
With pyridine; N,N'-carbonyldi<2(3H)-benzoxazolethione 1) N-methyl-2-pyrrolidone, r.t., 2 h, 2) TEA, 4 d; Yield given. Multistep reaction; | ||
22 % Chromat. | With [Cl(C6F13C2H4)2SnOSn(C2H4C6F13)2Cl]2 In various solvent(s) at 150℃; for 16h; | |
With silica gel; iron(III) perchlorate In dichloromethane Heating; | ||
With dmap; oligomeric alkyl cyclohexylcarbodiimide In dichloromethane at 20℃; for 2h; | ||
82 % Chromat. | With zirconium(IV) oxychloride In toluene for 8h; Heating; | |
21 % Chromat. | With perfluoro(methylcyclohexane) In 1,2-dichloro-ethane at 50℃; for 24h; | |
In toluene for 24h; Heating; | ||
With dmap; 2-chloro-1-(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,12,12,12-henicosafluorododecyl)pyridinium trifluoromethanesulfonate; triethylamine In N,N-dimethyl-formamide at 20℃; for 0.5h; | ||
With dmap; 2-chloro-1-(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,12,12,12-henicosafluorododecyl)pyridinium trifluoromethanesulfonate; triethylamine In N,N-dimethyl-formamide at 20℃; for 0.5h; | 4.1.2. A typical procedure for the coupling reaction and purification using 3d General procedure: To a solution of benzoic acid (62.8 mg, 0.51 mmol), aniline (47 μl, 0.51 mmol) and DMAP (62.8 mg, 0.51 mmol) in dry DMF (8 ml) was added the fluorous Mukaiyama reagent 3d (500 mg, 0.61 mmol) at room temperature. The reaction mixture was stirred for 1 h at ambient temperature. After the addition of H2O (2 ml), the reaction mixture was stirred for an additional 5 min and then filtered. After washing the precipitate with 20% aq DMF (10 ml), 1.0 M HCl was added to the filtrate, which was then extracted with diethyl ether. The organic layer was then washed again with1.0 M HCl and brine. After drying the organic layer with Na2SO4, concentration of the organic phase provided the coupling product in quantitative yield (101 mg), in high purity (99%). | |
96 %Chromat. | With tris(1-glycyl-3-methyl imidazolium chloride-iron(III)) In neat (no solvent) at 25℃; for 6h; Green chemistry; | |
98 %Chromat. | With poly(ethylene glycol) 1000 based dicationic acidic ionic liquid In toluene at 80℃; for 1h; Ionic liquid; | General procedure for esterification in PEG1000-DAIL/toluene system General procedure: Aromatic acids (2 mmol) and alcohols (3 mmol) were added into a 10 mL tube reactor preloaded with PEG1000-DAIL (2 mL) and toluene (2 mL). The reaction mixture was stirred thoroughly at 80C for 1 h. After the completion of reaction, the mixture separated into two phases at room temperature, the upper phase was decanted for analysis and the below phase was reused for the next time directly or after removing water under vacuum at 80C for 1 h. |
With oxalyl dichloride; triethylamine; Triphenylphosphine oxide In acetonitrile at 20℃; for 2h; Inert atmosphere; | 1 1.40 g of triphenylphosphine oxide was added to a 100 mL three-necked flask, evacuated to N2, 5 mL of acetonitrile was added,0.55mL of oxalyl chloride was slowly added dropwise, and the reaction was violent and a large amount of gas was released. The reaction was carried out for 10 minutes. Then, 0.61 g of benzoic acid, 0.67 mL of benzyl alcohol and a catalytic amount of triethylamine were added and reacted at room temperature for 2 hours. The reaction was followed by TLC, quantified by column chromatography and qualitative by NMR. (Petroleum ether / ethyl acetate) ratio of 4: 1, the yield of benzyl benzoate obtained by column chromatography was 85.37%, | |
109.3 mg | With dmap; dicyclohexyl-carbodiimide at 20℃; for 8h; Inert atmosphere; Green chemistry; | |
With nitrobenzene; triphenylphosphine; 3-methyl-2',3',4',5'-tetraacetylriboflavin at 40℃; for 24h; Molecular sieve; Irradiation; | ||
With hydrogenchloride; toluene unter Entfernen des entstehenden Wassers; | ||
Stage #1: benzoic acid With 1,2-dibromo-1,1,2,2-tetrachloroethane; triphenylphosphine In dichloromethane at 20℃; Stage #2: benzyl alcohol In dichloromethane at 20℃; for 0.5h; | 3.4. General procedure for conversion to acid derivatives General procedure: PPh3 (1.1 mmol) was dissolved in freshly distilled dichloromethane (4.0 mL) at 20 °C. A solution of DBTCE (1.1 mmol) in freshly distilled dichloromethane (4.0 mL) was added to the solution dropwise and the white colloidal mixture was stirred for 2 min. Benzoic acid (1.0 mmol) in freshly distilled dichloromethane (4.0 mL) was added to the mixture dropwise. The resulting solution was stirred for 30 min and amine (1.1 mmol) or alcohol (1.1 mmol) was added to the mixture followed by stirring for 30 min. The mixture was purified by flash column on 20 g of silica gel using a mixture of petroleum ether/EtOAc (1:1). | |
With acrylic resin containing recombinant lipase from Candida antarctica at 25℃; for 24h; Enzymatic reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With 1,3-bis(3,5-bis(trifluoro-ethyl)phenyl)thiourea; 4-pyrrolidin-1-ylpyridine In octane for 24h; Reflux; | |
100% | With dilithium tetra(tert-butyl)zincate at 0℃; for 1h; Inert atmosphere; | General procedure: A typical procedure was as follows. Vinyl acetate (5.0mmol), benzyl alcohol (1.0mmol), and solvent (2.0mL) were added to a glass ampoule which had been degassed and filled with nitrogen. A solution of TBZL (0.1mmol) in THF was added under a nitrogen atmosphere to the ampoule placed in a constant-temperature bath. Then the mixture was kept at 25 or 0°C and stirred. After a prescribed period, the mixture was diluted with CDCl3 and transformed in a NMR tube. Conversion of the reaction was determined by 1H NMR at 400MHz. |
97% | With lanthanum(III) isopropoxide; 2-(2-methoxyethoxy)ethyl alcohol In hexane Reflux; chemoselective reaction; |
97% | With iron(III)-acetylacetonate; sodium carbonate In n-heptane at 105℃; for 6h; Inert atmosphere; | 5.4. Representative transesterification procedure catalyzed by Fe(acac)3 and Na2CO3 as additive To a 25 mL, one-necked, round-bottomed flask was placed Fe(acac)3 (36 mg, 0.10 mmol, 5 mol %), benzyl alcohol (216 mg, 208 μL, 2 mmol), and Na2CO3 (10.6 mg, 0.10 mmol, 5 mol %) in 10 mL heptane at room temperature under nitrogen atmosphere. A solution of methyl benzoate (272 mg, 256 μL, 2 mmol) in heptane (10 mL) was added via syringe. The resulting mixture was heated to reflux with the removal of the methanol by Dean-Stark apparatus and the reaction progress was monitored by TLC, 1H NMR spectroscopy, and GC analysis until completion of the reaction (6 h). The reaction mixture was then gradually cooled to room temperature and quenched with saturated aqueous NH4Cl solution (5 mL), then extracted with 20 mL ethyl acetate. The combined organic layer was dried (anhydrous MgSO4), filtered, and evaporated to give a crude product that was purified by column chromatography on silica gel (hexane/AcOEt=50/1) to provide the pure benzyl benzoate product 412 mg, 97% yield. |
97% | With Co3(μ2-OH)(μ2-OCOtBu)4(η2-OCOtBu)2(2,2’-bipyridine)2 In toluene for 5h; Reflux; Inert atmosphere; Schlenk technique; | |
97% | With oxo[hexa(trifluoroacetato)]tetrazinc; C19H24N4O In toluene for 5h; Reflux; | 14 Examples 11 to 14 Transesterification Reactions Examples 11 to 14 Transesterification Reactions (0162) Reactions were conducted as shown in the following formula by changing the solvent to toluene and by using Zn4(OCOCF3)6O (1 mole equivalent) and various ligands (8 mole equivalents, each ligand was 2 mole equivalents relative to 1 mole equivalent of zinc atoms) as catalysts, which were added to a transesterification reaction system between methyl benzoate and benzyl alcohol (catalyst ratio: 1.25 mol %). (0163) Table 3 below collectively shows the reaction results. [table-us-00003-en] Ligand Yield (%) Example 11 91 Example 12 92 Example 13 97 Example 14 97 (0164) When the ligand (D) of Example 14 was used as the catalyst, the system remained homogeneous one hour after the start of the reaction, but a solid was precipitated at the end of the reaction. The precipitated solid was recovered. The zinc complex C of the present invention serving as the catalyst was successfully recovered in a yield of 63%. A transesterification reaction was conducted by using the recovered zinc complex C in the same manner. The reaction proceeded in about the same yield (92%). Hence, it is conceivable that the catalyst of the present invention can provide good results, even when recycled. |
96% | With potassium phosphate; N-benzyl-N,N,N-triethylammonium chloride at 20℃; for 24h; | |
92% | In toluene for 15h; Heating; | |
90% | With potassium <i>tert</i>-butylate; 1,2,3,4,5-pentamethyl-1H-imidazol-3-ium iodide In tetrahydrofuran at 20℃; for 1.5h; Molecular sieve; | |
89% | With [{lμ2-3-1κO-((carboxylatomethyl)amino)-4-chlorobenzoato}(N,N,N-κ3-2,3,5,6-tetrakis(2-pyridyl)pyrazine)zinc(II)]n(dimethylformamide)(water) In dimethyl sulfoxide at 80℃; for 4h; | General synthetic procedure for transesterification reactions (products 6a-6f) General procedure: MOF 1 (2.0 mol%) dissolved in DMSO (10 mL), was subjected to a well dried round bottom flask equipped with a magnetic stirring bar and reflux condenser. To the solution of catalyst 1, ester 4a-4f (1.0 mmol) and alcohol 5a-5f (1.2 mmol) were added at room temperature. The resulting reaction mixture was further refluxed at 80 °C in open air atmosphere. The progress of reaction was monitored by TLC and the reaction was terminated after consumption of the starting material. The DMSO solution containing transesterification product was evaporated under reduced pressure at 60 °C and the resulting crude product was purified by flash column chromatography which afforded the desired products 6a-6f. |
65% | With tetraethylammonium bicarbonate at 60℃; for 2h; | Synthesis of benzyl benzoate 4ca The procedure for the synthesis of 4ca was the same reported above, but 1 mmol of benzyl alcohol and 1 mmol of methyl benzoate were added sequentially to the catalyst 1a (30% mol). Ester 4ca was isolated in 65% yield. It was purified using flash chromatography (hexane-CH2Cl2 90:10) and identified by NMR spectroscopy by comparison with the data reported in the literature. |
63% | With platinum; 1-butyl-3-methylimidazolium Tetrafluoroborate at 20 - 60℃; for 2h; Inert atmosphere; Electrochemical reaction; Green chemistry; | |
With Potassium benzoate | ||
With fluorapatite-like natural phosphate In toluene at 110℃; for 48h; | ||
97 %Chromat. | With heterogeneous zinc/imidazole catalyst In toluene at 120℃; for 2h; Inert atmosphere; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With N,N,N',N'',N'''-pentamethyldiethylenetriamine In neat (no solvent) at 20 - 25℃; for 8h; | 4.2 PMDETA-catalyzed benzoylation of alcohols with trichloromethyl phenyl ketone (1) General procedure: General procedure: In a 25 mL round bottom flask, trichloromethyl phenyl ketone (0.447 g, 2 mmol), alcohol (2 mmol; 0.077 g, 2.4 mmol in the case of methanol), and PMDETA (0.007 g, 0.04 mmol; 0.035 g, 0.2 mmol in case of secondary alcohols) were taken without any solvent. The flask was stoppered and the mixture was stirred at room temperature (20-25 °C) on a magnetic stirrer. The progress of the reaction was monitored by TLC. After the completion of the reaction (10 min to 48 h), the crude reaction mixture was purified by flash column chromatography using n-hexane or ethyl acetate (5-10% v/v) in n-hexane as the solvent for elution to furnish the benzoate esters (Table 2) in 82-96% yield. |
81% | With 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran at 25 - 50℃; for 12h; | |
75% | With triethylamine In water; acetonitrile at 20℃; | A typical procedure for one-pot synthesis of ester from an alkynylsilane General procedure: A mixture oftrimethyl(phenylethynyl)silane 1a (0.5 g, 2.87 mmol), KCl (0.642 g, 8.62 mmol), oxone(2.65 g, 8.62 mmol) and acetonitrile-water (2:1) was taken into a round bottomed flask andstirred at room temperature for 25 minutes. The progress of the reaction was monitored byTLC. After formation of 2a, to this reaction mixture methanol (0.091 g, 2.87 mmol) andtriethylamine (0.29 g, 2.87 mmol) was added and continued the stirring at room temperature.After completion of the reaction (by TLC) , organic layer was extracted with ethyl acetate(3x10 mL) and washed with brine (1x10 mL), dried over anhydrous Na2SO4 andconcentrated under reduced pressure. Purification of the crude product by normal columnchromatography (silica gel 60-120 mesh) furnished methylbenzoate 10a |
With sodium benzoate; xylene |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With C56H70Cl3N10Ru2(1+)*F6P(1-); potassium-t-butoxide; hydrogen In tetrahydrofuran; dodecane at 70℃; for 16h; Inert atmosphere; Glovebox; Autoclave; | |
99% | With dichloro(benzene)ruthenium(II) dimer; 2-((di-p-tolylphosphino)methyl)-1-methyl-1H-imidazole; potassium-t-butoxide; hydrogen In tetrahydrofuran at 100℃; for 2h; | |
99% | With C66H102N4OP2Ru; hydrogen In toluene at 105℃; for 20h; Inert atmosphere; Glovebox; |
99% | With dimethylsulfide borane complex In 2-methyltetrahydrofuran at 90℃; for 0.333333h; Inert atmosphere; Flow reactor; chemoselective reaction; | |
98% | With C32H34BrN5ORu; potassium methanolate; hydrogen In tetrahydrofuran at 100℃; for 16h; | |
95% | With [iPrPN(H)P]2Fe(H)(CO)(BH4); hydrogen In toluene at 115℃; for 3h; Glovebox; Sealed tube; | |
95% | With [bis({2‐[bis(propan‐2‐yl)phosphanyl]ethyl})amine](borohydride)(carbonyl)(hydride)iron(II); hydrogen at 115℃; for 3h; | |
95% | With C30H26Cl2N3PRu; hydrogen; potassium etoxide In toluene at 80℃; for 16h; Autoclave; Inert atmosphere; Schlenk technique; | |
92% | With C18H28Br2N4Ru; potassium-t-butoxide; hydrogen In 1,4-dioxane at 105℃; for 8h; | 2.10. Typical procedure for the catalytic hydrogenation General procedure: To a mixture of catalyst (0.01 mmol), KOtBu (10 mol %), and 1,4-dioxane (4.0 mL) in a Parr high-pressure reactor was added the ester(1.0 mmol). The dark red solution was purged with H2 and stirred under 400 psi of H2 at 105 °C for 8 h. Products isolation were performed via column chromatography using silica gel as stationary phase and n-pentane/ethylacetate or n-pentane/isopropanol mixture as eluent. The products were confirmed by 1H NMR. |
92% | With C30H34Cl2N2P2Ru; potassium methanolate; hydrogen In tetrahydrofuran at 100℃; for 15h; Glovebox; Autoclave; | 27 Example 27: Hydrogenation of ester compounds catalyzed by ruthenium complex Ia General procedure: In a glove box, add a ruthenium complex Ia (0.3 to 0.7 mg, 0.0002 to 0.001 mmol) to a 300 mL autoclave,Potassium methoxide (35-700 mg, 0.5-10 mmol), tetrahydrofuran (4-60 mL), and ester compounds (10-200 mmol).After sealing the autoclave, take it out of the glove box and fill it with 50 100atm of hydrogen.The reaction kettle was heated and stirred in an oil bath at 100 ° C for 10 to 336 hours.After the reaction kettle was cooled in an ice-water bath for 1.5 hours, the excess hydrogen was slowly released.The solvent was removed from the reaction solution under reduced pressure, and the residue was purified with a short silica gel column to obtain an alcohol compound. The results are shown in Table 5. |
92% | Stage #1: benzoic acid benzyl ester With phenylsilane; fac-[Mn-(xantphos)(CO)3Br] at 100℃; for 6h; Inert atmosphere; Stage #2: With sodium hydroxide In methanol; water monomer at 20℃; | |
89% | With C17H16BrMnNO3P; potassium-t-butoxide; hydrogen In 1,4-dioxane at 100℃; for 16h; Autoclave; | |
89% | With C30H37ClN4ORu; hydrogen; sodium tertiary butoxide In toluene at 105℃; for 20h; Glovebox; Sealed tube; | |
88% | With sodium hydroxide; tetrabutylammonium hydrogensulfate In tetrahydrofuran at 20℃; for 3h; | |
87% | With H2SiEt2; C15H27Br2CoN3; potassium-t-butoxide In toluene at 50℃; for 0.333333h; Inert atmosphere; Glovebox; Sealed tube; | |
86% | With phenylsilane; potassium-t-butoxide; water monomer; sodium triethylborohydride; cobalt(II) chloride In 1,4-dioxane; toluene at 60℃; for 15h; Inert atmosphere; Glovebox; Schlenk technique; | |
86% | With ethanol; [bis({2‐[bis(propan‐2‐yl)phosphanyl]ethyl})amine](borohydride)(carbonyl)(hydride)iron(II) at 100℃; for 24h; Inert atmosphere; Sealed tube; Darkness; | |
85% | With sodium tetrahydridoborate; [fac-PNN]RuH(PPh)3(CO); hydrogen In tetrahydrofuran at 120℃; for 12h; Inert atmosphere; Autoclave; | |
83% | Stage #1: benzoic acid benzyl ester With phenylsilane In tetrahydrofuran at 20℃; for 18h; Stage #2: With sodium hydroxide In methanol; water monomer | |
82% | With n-butyllithium; [(1,2-bis[(2,6-diisopropylphenyl)imino]acenaphthene)FeCl2] In hexane; toluene at 100℃; for 20h; Inert atmosphere; Schlenk technique; Glovebox; Sealed tube; | |
77% | With benzo-15-crown-5; (1-(2-(2,3-diisopropyl-1-methylguanidino)ethyl)-3-mesityl-1,3-dihydro-2H-imidazol-2-ylidene)copper(I) chloride; hydrogen; sodium tertiary butoxide In 1,4-dioxane at 60℃; for 24h; Inert atmosphere; | |
74% | With ethanol; RuCl2(PPh3)[(EtSC2H4)2NH]; potassium-t-butoxide In toluene at 80℃; for 16h; | |
67% | With [RuCl2(N-heterocyclic carbene)(bis[2-(diphenylphosphino)ethyl]amine)]; potassium-t-butoxide; hydrogen In tetrahydrofuran; 2-methyltetrahydrofuran at 45℃; for 2.5h; Autoclave; | |
66% | With potassium-t-butoxide; hydrogen; C31H35MnN5O3(1+)*F6P(1-) In tetrahydrofuran at 100℃; for 48h; | |
9% | With HN(CH2CH2C3H3N2Mes)2Cl2; potassium-t-butoxide; hydrogen; cobalt(II) chloride In tetrahydrofuran at 100℃; for 16h; Autoclave; Glovebox; | |
98 % Chromat. | With sodium tetrahydridoborate In methanol; <i>tert</i>-butyl alcohol Heating; | |
95 % Spectr. | With hydrogen; triethylamine In various solvent(s) at 120℃; for 16h; | |
99 % Chromat. | With hydrogen; sodium methoxide In tetrahydrofuran at 100℃; for 1h; | |
With hydrogen In tetrahydrofuran at 80℃; for 16h; | 13 Example 13Hydrogenation of Benzyl Benzoate Benzyl benzoate (8 mmol), a ruthenium complex 1 (0.008 mmol), and tetrahydrofuran (3.2 mL) were charged into a 100-mL autoclave equipped with a stirrer. Then, the mixture was subjected to hydrogenation at a hydrogen pressure of 5 MPa at 80° C. for 16 hours. The reaction liquid was analyzed by gas chromatography. As a result, benzyl alcohol was obtained at a conversion rate of 23% and a selectivity of 98%. | |
With C42H38N4OPRu(1+)*Cl(1-); potassium-t-butoxide; hydrogen In toluene at 100℃; for 2h; | ||
99 %Chromat. | With [RuH(η2-BH4)(2-di-tert-butylphosphinomethyl-6-diethylaminomethylpyridine)]; hydrogen In tetrahydrofuran at 110℃; for 12h; Autoclave; | |
72 %Chromat. | Stage #1: benzoic acid benzyl ester With iron(II) stearate; Ethane-1,2-diamine In toluene at 20℃; for 0.0833333h; Inert atmosphere; Schlenk technique; Stage #2: In toluene at 100℃; for 20h; Inert atmosphere; Schlenk technique; | |
With C19H27ClN3OPRu; potassium-t-butoxide; hydrogen In toluene at 120℃; Inert atmosphere; Schlenk technique; | ||
86 %Chromat. | With [bis({2‐[bis(propan‐2‐yl)phosphanyl]ethyl})amine](borohydride)(carbonyl)(hydride)iron(II); hydrogen In tetrahydrofuran at 120℃; for 19h; Autoclave; | |
92 %Chromat. | With 1,1'-methylene-bis(3-benzyl-1H-imidazol-3-ium) diiodide; di-μ-chlorobis-[(η6-p-cymene)chlororuthenium(II)]; potassium-t-butoxide; hydrogen In 1,4-dioxane at 100℃; for 6h; | |
> 99 %Chromat. | With [RuCl2(2-(diphenylphosphino)-N-((6-((diphenylphosphino)methyl)pyridin-2-yl)methyl)ethan-1-amine)]; potassium-t-butoxide; hydrogen In tetrahydrofuran at 80℃; for 5h; Autoclave; | |
With hydrogen; potassium etoxide In 1,4-dioxane at 80℃; for 16h; | ||
98 %Spectr. | With C27H31ClN4ORu; hydrogen; sodium tertiary butoxide In toluene at 105℃; for 20h; | |
With tris(triphenylphosphine)ruthenium(II) chloride; 2-diphenyl-1,2-ethylenediamine; potassium-t-butoxide; hydrogen In tetrahydrofuran at 60℃; for 16h; | ||
With sodium tetrahydridoborate; [fac-8-(2-diphenylphosphinoethyl)amidotrihydroquinoline]RuH(PPh3)(CO); hydrogen In tetrahydrofuran at 120℃; for 12h; Autoclave; Industrial scale; | 2-4 Example 2-3-2-4 General procedure: In a 100 mL glass jar,(1) 7 · 51 mg (0.01 mmol), NaBH 4 37.8 mg (1 mg)Ethyl benzoate 3.00 8 (20: 1: 3: 8 {= 2000: 20: 1)Solvent 50 11 ^, the reaction system into the 100 mL high pressure reactor, the replacement of hydrogen three times, into the hydrogen at 50 atm, the temperature is set to 120 ° C,Heating and stirring reaction time 12 hours,The reaction vessel was cooled in an ice bath to room temperature and vented. GC analysis of the reaction solution, the results shown in Table 2. Except that n-butyl benzoate (Example 2-3), Benzyl benzoate (Example 2-4) was used instead of ethyl benzoateThe hydrogenation reduction was the same as in Example 2-1, and the results are shown in Table 2 | |
99 %Chromat. | With hydrogen; potassium etoxide In 1,4-dioxane at 80℃; for 16h; Autoclave; | 11 Being placed in a magnetic sub 5ml glass bottle, washed added NaOEt (17mg, 0.25mmol), Catalyst E (0.38mg, 0.001mmol), to benzyl benzoate (1.061g, 5mmol, S / C = 10000: 1) solvent dioxane (2.5mL), the above reaction system into the autoclave, punch-for-hydrogen three times, filled with hydrogen 50atm, the reactor was placed in an oil bath at 80°C pot, heating and stirring 16h, the the reaction vessel was cooled in an ice bath.Analysis by gas chromatography of the reaction system (SPBTM-5, FUSED SILICA Capillary Column, 30m × 0.25mm × 0.25μm, filmthickness), injection temperature 250°C, detector temperature 260°C, temperature program 120°C (0°C)-20°C/min-240°C(0min).Gas chromatographic analysis in 99% yield. |
99 %Spectr. | With C21H35BrMnN2O2P; hydrogen; potasssium hydride; 1,3,5-trimethyl-benzene In toluene at 100℃; for 43h; Autoclave; Inert atmosphere; | |
Multi-step reaction with 2 steps 1: sodium tetrakis[(3,5-di-trifluoromethyl)phenyl]borate; C24H23ClCrIrNO3 / dichloromethane / 1 h / 25 °C / Schlenk technique; Glovebox; Inert atmosphere 2: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 12 h / Inert atmosphere | ||
99 %Spectr. | With C21H35BrMnN2O2P; hydrogen; potasssium hydride In toluene at 100℃; for 43h; | 16 Hydrogenation of 1 mmol of hexyl hexanoate under 20 bar at 100°C in toluene, resulted in 99% yield of hexanol (Entry 1). Under the same conditions ethyl butyrate was hydrogenated to give 98% yield of butanol and 91 % yield of ethanol after 50 hours (Entry 2). When the reaction was performed at shorter reaction time (22 hours, Entry 2bis), small amounts of ethyl acetate and butyl butanoate were also formed, attributed to a transesterification reaction with the formed ethanol and butanol. Cyclohexylmethyl acetate gave 99% yield of cyclohexylmethanol and 60% yield of ethanol (Entry 3), and no transesterification products were observed. Hydrogenation of the secondary aliphatic ester heptan-2-yl acetate resulted in 98% yield of heptane-2-ol and 57% yield of ethanol (Entry 4). Ethyl 3-phenylpropanoate was smoothly hydrogenated, rendering 99% yield of 3-phenylpropan-l-ol and 70% yield of ethanol after 21 hours (Entry 5). Similarly, ethyl 3- phenylpropanoate gave 99% yield of phenyknethanol and 74% yield of butanol after 22 hours (Entry 6). In order to get full hydrogenation of benzyl benzoate longer reaction time was needed (43 hours, 99% yield benzyl alcohol, Entry 7). Similarly, methyl benzoate gave 96% yield of benzyl alcohol and 63 % of methanol after 50 hours (Entry 8). ε-Caprolactone was smoothly and quantitatively hydrogenated to 1 ,6-hexanediol (99% yield, Entry 9). The activated benzyl trifluoroacetate gave 99% yield of benzyl alcohol and 78% of 2,2,2- trifluoroethanol (Entry 10), and no secondary products where observed. Gratifyingly, allyl trifluoroacetate gave 97% yield of 2,2,2-trifluoroethanol and 96% of allyl alcohol (Entry 1 1), showing high chemoselectivity to ester hydrogenation over C=C hydrogenation. Hydrogenation of ethyl 4-isocyano-benzoate required an increase of precatalyst loading to 3%, probably due to competing nitrile coordination, and resulted in 61 % yield of (4-isocyanophenyl)methanol and 66% yield of ethanol, with no hydrogenation of the nitrile group detected (Entry 12). |
97 %Chromat. | With [{CyPN(H)P}Co(CH2SiMe3)]-BArF4; hydrogen In tetrahydrofuran at 120℃; for 20h; | |
26 %Chromat. | With dichlorido-bis[(2-diphenylphosphino)ethyl]amine-cobalt(II); hydrogen; sodium methoxide In 1,4-dioxane at 120℃; for 24h; Autoclave; | |
With C43H42NOP3Ru; hydrogen In 1,4-dioxane; methanol at 130℃; for 17h; Glovebox; Autoclave; | ||
With potassium-t-butoxide; hydrogen In tetrahydrofuran at 80℃; for 16h; Autoclave; Glovebox; | ||
99 %Chromat. | With C36H62N2OP2Ru; hydrogen In isopropanol at 25℃; for 16h; Autoclave; | |
Multi-step reaction with 2 steps 1: 2C16H16N2O2(4-)*8Li(1+)*8C4H8O / tetrahydrofuran / 2 h / 60 °C / Inert atmosphere 2: mesoporous silica; methanol / 2 h / 50 °C | ||
With hydrogen; (<SUP>Cy</SUP>PN<SUP>H</SUP>P)FeH(CN<SUP>t</SUP>Bu)(BH<SUB>4</SUB>) In tetrahydrofuran at 110℃; for 4h; Schlenk technique; Glovebox; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With 3-mesityl-4-methylthiazol-3-ium bis((trifluoromethyl)sulfonyl)imide; dimethyl sulfoxide; 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran Electrochemical reaction; Inert atmosphere; Flow reactor; | |
85% | With 1,2-diphenyl-1,1,2,2-tetrahydroperoxyethane; hydrogen bromide; acetic acid In water at 20℃; for 6h; | Oxidative esterification (Scheme 2, entry 10) General procedure General procedure: A mixture of aldehyde (1 mmol), alcohol (2 mL), acetic acid (glacial, 0.1 mmol) and THPDPE (1 mmol) was stirred at room temperature. After the peroxide was dissolved, HBr (47% aq, 0.1 mmol) was added. After the completion of the reaction as monitored by thin-layer chromatography (TLC), the mixture was diluted with saturated NaCl solution (5 mL) and extracted with CHCl3 (3×5 mL). Then, organic layer was separated, dried over anhydrous Mg2SO4 and evaporated under reduced pressure. The residue was purified by silica- packed column chromatography (Hexane-EtOAc) to afford esters. Products were characterized on the basis of their melting points, elemental analysis and IR, 1H-NMR, and 13C-NMR spectral analysis. |
82% | With ammonium peroxydisulfate at 60℃; for 8h; |
81% | Stage #1: benzyl alcohol With 1,8-diazabicyclo[5.4.0]undec-7-ene; 1,4-dimethyl-1,2,4-triazolium iodide; benzylamine In tetrahydrofuran for 0.0833333h; Inert atmosphere; Stage #2: benzaldehyde With 3,5,3',5'-tetra-tert-butyl-4,4'-diphenoquinone In tetrahydrofuran at 20℃; for 6h; Inert atmosphere; chemoselective reaction; | |
76% | With 2-mesityl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-2-ium tetrafluoroborate; tris(2,2′-bipyrazine-N1,N1′)ruthenium(II) hexafluorophosphate; 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine In acetonitrile at 20℃; | |
74% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; 1,3-bis-(2,6-diisopropylphenyl)-imidazol-2-ylidene In toluene at 100℃; for 4h; Inert atmosphere; | |
72% | With diphenyl acetylene at 147℃; for 2h; | |
72% | With 4-ethyl-1-methyl-4H-[1,2,4]-triazol-1-ium iodide; 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran at 45℃; for 24h; | |
67% | With potassium <i>tert</i>-butylate In benzene at 125℃; for 24h; Glovebox; Inert atmosphere; Sealed tube; | |
64% | With FeMo6O24(9-)*3H3N*9H(1+); potassium chloride; dihydrogen peroxide; nitric acid at 65℃; for 24h; Schlenk technique; | |
60% | With urea-2,2-dihydroperoxypropane; hydrogen bromide; acetic acid at 20℃; for 7h; | |
55% | With triethylamine; Azobenzene In tetrahydrofuran | |
15% | With perchloric acid; sodium percarbonate; vanadia for 2h; Cooling; | |
93 %Chromat. | With [RuHCl(CO)(4,5-bis(diisopropylphosphinomethyl)acridine)] In 1,3,5-trimethyl-benzene for 24h; Reflux; Inert atmosphere; | |
Multi-step reaction with 2 steps 1: 70 - 75 °C 2: dihydrogen peroxide / 8 h / 70 - 75 °C | ||
With ozone Neat (no solvent); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With potassium hydroxide at 100℃; for 6h; Autoclave; | |
97% | With triethylamine at 100℃; for 1.5h; Inert atmosphere; | |
94% | With triethylamine at 100℃; for 2h; Autoclave; |
91% | With 1,8-diazabicyclo[5.4.0]undec-7-ene In benzene at 120℃; for 3h; | |
91% | With 1,8-diazabicyclo[5.4.0]undec-7-ene at 80℃; for 6h; | Typical procedure for carbonylation reactions General procedure: The catalytic reactions were carried out in a 10 mL reaction flask and fitted with condenser and carbon monoxide balloon. In a typical run, a catalyst containing 1.0 mol% Pd, aryl iodide (0.5 mmol) and DBU (1.5 mmol) were added to solvent and allowed to react under CO atmosphere at 80 °C temperature for 6-10 h. After the reaction,the flask was cooled to room temperature and carbon monoxide balloon was removed. The reaction mixture was then centrifuged and the clear supernatant was analyzed with GC by using n-butanol as an internal standard. For the study of substrate scope, after completion of the reaction, the catalyst was centrifuged and extracted with copious ethanol. The obtained liquid was concentrated. For phenoxycarbonylation, the obtained liquid was diluted with saturated NH4Cl and extracted with diethyl ether. The organic layer was dried over anhydrous Na2SO4 and then concentrated. The product was obtained by preparative thin-layer chromatography (PTLC) using petroleum ether and ethyl acetate (30:1, v/v) as eluting solvent. The purity of products was checked by NMR and yields were based on aryl iodides. |
90% | With triethylamine; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; palladium dichloride In tetrahydrofuran at 80℃; for 16h; | |
89% | With triethylamine at 80℃; for 3h; Autoclave; | |
74% | With palladium 10% on activated carbon; 1,8-diazabicyclo[5.4.0]undec-7-ene In N,N-dimethyl-formamide at 130℃; for 0.166667h; Microwave irradiation; | |
70% | With triethylamine In benzene at 140℃; for 6h; | |
62% | With palladium diacetate; triethylamine at 110 - 120℃; for 7h; | |
52% | With C33H28Cl2N3PPd; triethylamine | |
28 %Spectr. | With palladium diacetate; potassium carbonate at 60℃; for 12h; Green chemistry; chemoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With titanium(IV) isopropylate Heating; Fluorinert Fluid, Dean-Stark trap; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With C39H31BMnNO2P2; potassium hydride at 150℃; for 24h; | |
98% | With C42H36ClIrO2P2; caesium carbonate In para-xylene for 36h; Inert atmosphere; Reflux; | |
97% | With oxygen In toluene at 100℃; for 18h; |
97% | With oxygen; potassium carbonate at 80℃; for 20h; | |
96% | With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; benzyl chloride In tetrahydrofuran at 65 - 70℃; for 20h; Inert atmosphere; Schlenk technique; | |
95% | With caesium carbonate; 1,8-diazabicyclo[5.4.0]undec-7-ene In 1,3,5-trimethyl-benzene at 157℃; for 48h; | |
94% | at 160℃; for 12h; Inert atmosphere; | 1.1.5 For catalytic dehydrogenative esterification of primary alcohols, a mixture of Ruthenium complex (0.01 mmol) and alcohol (10 mmol) was heated under an argon flow at the temperature shown in Table 1. |
94% | With oxygen; caesium carbonate In water at 50℃; for 12h; | |
94% | With C25H27BF3N7NiO In toluene for 24h; Glovebox; Schlenk technique; Reflux; Inert atmosphere; | |
94% | With C36H32Cl2N2O2P2Ru; sodium hydroxide In toluene at 150℃; for 16h; Inert atmosphere; Schlenk technique; | |
93% | With potassium carbonate; butanone at 20℃; for 25h; | |
91% | With C30H43ClCoN2P3(1+)*Cl(1-); potassium <i>tert</i>-butylate In benzene at 125℃; for 24h; Inert atmosphere; Sealed tube; | |
90% | With copper(l) iodide; di-tert-butyl peroxide; (E)-N-((Z)-4-((2,6-dimethylphenyl)amino)pent-3-en-2-ylidene)-2,6-dimethylaniline In neat (no solvent) at 90℃; for 6h; Sealed tube; Inert atmosphere; | |
90% | With RuH(CO)Cl(PPh3)(κ2-CP); caesium carbonate In toluene at 110℃; for 26h; Schlenk technique; Glovebox; Inert atmosphere; | |
88% | With OsH4[HN(C2H4Pi-Pr2)2] at 205℃; for 4h; Inert atmosphere; | |
88% | With [RuH(η2-BH4)(2-di-tert-butylphosphinomethyl-6-diethylaminomethylpyridine)] In toluene at 115℃; for 24h; Inert atmosphere; | |
88% | With [bis({2‐[bis(propan‐2‐yl)phosphanyl]ethyl})amine](borohydride)(carbonyl)(hydride)iron(II) In toluene at 120℃; for 8h; Glovebox; Schlenk technique; Inert atmosphere; | |
88% | With [{Cu2(5-phenyl-2,8-bis(6′-bipyridinyl)-1,9,10-anthyridine)-(μ-ClO4)2}(PF6)2]; dihydrogen peroxide; sodium acetate In water at 70℃; for 12h; | |
88% | With chloro(1,5-cyclooctadiene)rhodium(I) dimer; caesium carbonate; ortho-nitrofluorobenzene In toluene at 115℃; for 20h; Schlenk technique; Sealed tube; | |
86% | With 1H-imidazole; tert.-butylhydroperoxide; tetra-(n-butyl)ammonium iodide In water at 80℃; for 8h; Green chemistry; chemoselective reaction; | To a mixture of benzyl alcohol (108 mg, 1.0 mmol) and TBHP(180 mg, 2.0 mmol) in water (5 ml), the catalyst TBAI (73.8 mg,0.2 mmol) and imidazole (136 mg, 2.0 mmol) were added, andthe mixture was stirred at 80 °C for 8 h. The progress of thereaction was monitored by thin layer chromatography (TLC).After completion of reaction, the reaction mixture was cooledto room temperature. Then the organic product was extractedwith ethyl acetate (3 × 10 ml), repeatedly washed with distilledwater (4 × 5 ml) to remove the unreacted TBHP, dried withanhydrous sodium sulfate, and the solvent was evaporatedunder reduced pressure to afford benzyl benzoate (182 mg,yield 86%). |
85% | With silver(I) hexafluorophosphate; oxygen; palladium diacetate; potassium carbonate; 1,2-bis[di(t-butyl)phosphinomethyl]benzene In toluene at 110℃; for 20h; chemoselective reaction; | |
85% | With [bis(2-methylallyl)cycloocta-1,5-diene]ruthenium(II); (2-((2-(diphenylphosphanyl)ethyl)(quinolin-2-ylmethyl)amino)ethyl)diphenylphosphine oxide; potassium <i>tert</i>-butylate In n-heptane at 100℃; for 16h; | |
85% | With oxygen; palladium diacetate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In toluene at 100℃; for 48h; | |
83% | With dodecatungstosilic acid; potassium chloride; dihydrogen peroxide; C5H12CrMo6O25(3-)*3C16H36N(1+) In water at 65℃; for 36h; Schlenk technique; | |
80% | With diphenyl acetylene at 147℃; for 2h; | |
80% | With C43H42NOP3Ru In toluene at 135℃; for 18h; Inert atmosphere; Glovebox; Schlenk technique; | |
68% | With potassium hydroxide In acetonitrile at 70℃; | |
60% | In neat (no solvent) at 180℃; for 36h; Inert atmosphere; Green chemistry; | |
60% | With [RuCl2{(S)-2-((diphenylphosphino)methyl)pyrrolidine}2]; zinc(II) trifluoroacetate; potassium hexamethylsilazane for 18h; Reflux; | |
58.7% | With oxygen; potassium carbonate In n-heptane at 30℃; for 3h; Irradiation; | |
42% | With C29H44Cl2N2Ru; potassium <i>tert</i>-butylate In toluene for 24h; Reflux; | |
31% | With [RuCl2(p-cymene)(iPr2-imy)]; potassium hydroxide; tricyclohexylphosphine In 1,3,5-trimethyl-benzene at 163℃; for 18h; Inert atmosphere; | |
97 % Chromat. | In toluene at 180℃; for 24h; | |
99.5 %Chromat. | With [RuHCl(CO)(4,5-bis(diisopropylphosphinomethyl)acridine)] In 1,3,5-trimethyl-benzene at 168℃; for 72h; Inert atmosphere; | |
With [Rh(trop2N)(PPh3)] In tetrahydrofuran Inert atmosphere; | ||
20 %Chromat. | With C24H28N4ORu In toluene at 110℃; for 24h; | |
With trans-carbonyldihydrido(bis(2-(diisopropylphosphanyl)ethyl)amine)osmium at 205℃; for 2h; | ||
With nitrobenzene; potassium hydroxide; dibenzoyl peroxide In chlorobenzene at 140℃; for 24h; | ||
Multi-step reaction with 2 steps 1: ozone / Neat (no solvent) 2: ozone / Neat (no solvent) | ||
With C19H31N3O2PRu at 160℃; for 12h; Inert atmosphere; | ||
Multi-step reaction with 2 steps 1: thionyl chloride; pyridine / dichloromethane 2: [D3]acetonitrile / 35 °C / Irradiation | ||
90 %Spectr. | With C44H35ClO4P2Ru; caesium carbonate In 5,5-dimethyl-1,3-cyclohexadiene for 24h; Inert atmosphere; Reflux; | |
66 %Chromat. | With (PPhenP-H)RuH In toluene for 72h; Inert atmosphere; Reflux; | |
85%Chromat. | With potassium phosphate; oxygen In n-heptane at 110℃; for 24h; Schlenk technique; Green chemistry; | |
70 %Chromat. | With sodium tetrachloroaurate(III) dihyrate; potassium carbonate In neat (no solvent) at 80℃; Green chemistry; | |
70 %Chromat. | With sodium tetrachloroaurate(III) dihyrate; potassium carbonate at 80℃; for 24h; Green chemistry; | |
43 %Chromat. | With oxygen In n-heptane at 55℃; for 24h; Irradiation; Sealed tube; Green chemistry; | |
With [bis({2‐[bis(propan‐2‐yl)phosphanyl]ethyl})amine](borohydride)(carbonyl)(hydride)iron(II) In toluene at 120℃; Glovebox; Schlenk technique; Inert atmosphere; | General Procedure for the Iron-Catalyzed Dehydrogenation of Alcohols General procedure: In a glovebox, a 50-mL flame-dried Schlenk flask equipped with a condenser was chargedwith an iron catalyst (25 μmol), an alcohol substrate (2.5 or 25 mmol), and 5 mLtoluene. The solution was stirred at 120 °C for a specific time under a constant N2flow. After the reaction, the solution was allowed to cool to room temperature,filtered through a short silica gel column, and eluted with THF. The resultingfiltrate was evaporated under vacuum to afford the pure product. | |
With oxygen; potassium carbonate In n-heptane at 100℃; for 24h; chemoselective reaction; | ||
With C33H59NOP2Ru In toluene; 1,3,5-trimethyl-benzene at 60℃; for 16h; Inert atmosphere; Glovebox; Schlenk technique; | ||
60.5 %Chromat. | With trans-[(2-(diphenylphosphanyl)-N-(pyridine-2-ylmethyl)ethaneamine)RuCl2(PPh3)]*dichloromethane; potassium <i>tert</i>-butylate In toluene for 8h; Inert atmosphere; Schlenk technique; Reflux; | |
With [Rh(1,3,4,5-tetramethylimidazole-2-ylidene)(trop2NH)][trifluoromethanesulfonate]; potassium <i>tert</i>-butylate; dinitrogen monoxide In tetrahydrofuran; toluene at -78 - 50℃; Molecular sieve; Schlenk technique; | ||
With 1,3,5-trimethyl-benzene In (2)H8-toluene at 110℃; Inert atmosphere; Schlenk technique; Glovebox; | ||
With calcium dichloride dihydrate; oxone; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; water In dichloromethane at 20℃; for 24h; | General procedure for oxidative esterification of primary alcohols General procedure: The respective alcohol (1.0 mmol) was added to a suspension of Oxone (400.0 mg, m., CaCl2*2H2O (73.5 mg, 0.5 mmol) and TEMPO (1.6 mg, 0.01 mmol) in dichloromethane (2 mL). The reaction was initiated by the addition of 0.1 mL DI water. The reaction mixture was stirred at RT for the indicated times or until TLC or GC/MS showed consumption of the starting material and then filtered. After evaporation of the solvent using a rotavap, the crude reaction mixtures were separated via column chromatography to yield the desired ester dimers. | |
With 1-butyl-3-methylimidazolium chloride; potassium hydroxide at 240℃; for 20h; | 3 In a 250 ml three-necked flask equipped with a water separator and a thermometer, 0.21 g of [Ru (1,5-cyclooctadiene) Cl 2] 2, 0.7 g of 1-methyl-3-n-butylimidazolium chloride , 5 g of potassium hydroxide and 100 g of benzyl alcohol. The mixture was heated to reflux for 20 hours while stirring (magnetic stirring) at an oil bath temperature of 240 ° C. at atmospheric pressure. After completion of the reaction, there were 10.4% unreacted starting material, 4.7% benzaldehyde (reaction intermediate), and 67.4% carboxylic acid ester (benzyl benzoate, conversion determined from GC area%) in the reaction mixture after completion of the reaction. The reaction product can be worked up as described in Example 1. | |
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / 0 - 20 °C / Inert atmosphere 2: di-isopropyl azodicarboxylate / dichloromethane / 36 h / 40 °C / Inert atmosphere | ||
With C20H28ClN2O2PRu; potassium <i>tert</i>-butylate In toluene at 117℃; for 15h; Schlenk technique; Inert atmosphere; | ||
With (2,6-bis(di-tert-butylphosphinito)pyridine)RuH(Cl)(CO); potassium hydroxide at 176℃; for 24h; Inert atmosphere; | 2.8 Experimental procedures for catalytic dehydrogenative coupling of alcohols to esters by (PONOP)RuH(Cl)(CO) in solution General procedure: 12mg of (PONOP)RuH(Cl)(CO) (0.02mmol) was placed in a small round-bottom flask. 20mmol of alcohol was added. The mixture was degassed by an applied vacuum and then heated with slow stirring under at inert atmosphere of argon. The reaction mixture was cooled to room temperature. The liquid product mixture was analyzed by GC-MS. Total alcohol conversion and reaction conditions for each alcohol are summarized in Table2 . | |
Multi-step reaction with 2 steps 1: C36H32Cl2N2O2P2Ru / toluene / 16 h / 150 °C / Inert atmosphere; Schlenk technique 2: C36H32Cl2N2O2P2Ru; sodium hydroxide / toluene / 150 °C / Inert atmosphere; Schlenk technique | ||
Multi-step reaction with 2 steps 1: C36H32Cl2N2O2P2Ru / tetrahydrofuran / 24 h / 170 °C / Inert atmosphere; Schlenk technique 2: C36H32Cl2N2O2P2Ru; sodium hydroxide / toluene / 150 °C / Inert atmosphere; Schlenk technique | ||
Multi-step reaction with 2 steps 1: C36H32Cl2N2O2P2Ru; potassium <i>tert</i>-butylate / toluene / 16 h / 150 °C / Inert atmosphere; Schlenk technique 2: C36H32Cl2N2O2P2Ru; sodium hydroxide / toluene / 150 °C / Inert atmosphere; Schlenk technique | ||
95 %Spectr. | With (bis[(2-diisopropylphosphino)ethyl]amine)Mn(CO)2 at 150℃; for 24h; Inert atmosphere; | |
6 %Chromat. | With iodine; sodium hydrogencarbonate In dichloromethane; water at 20 - 22℃; for 3h; | 1.6 Oxidation of alcohols 1a,b,h,k with I2 in a two-phase system CH2Cl2/NaHCO3(aq.) in the absence of nitroxides and pyridine co-catalysts General procedure: A solution of alcohol 1a,b,h,k (4.0 mmol) in CH2Cl2 (10 mL) was added to a magnetically stirred solution of NaHCO3 (1.0 g, 11.94 mmol) in water (10 mL) at 20-22 °C, then I2 (2.02 g, 7.96 mmol) powder was added in one portion to the formed two-phase mixture. The reaction mixture was stirred at 20-22 °C for 3 h. Then a saturated solution of sodium thiosulfate (3 mL) was added and the resulted mixture was stirred for 5 min, organic and aqueous phases were separated and analyzed by GC-MS (Table S06). |
With [fac-N-(2-(diphenylphosphino)ethyl)-5,6,7,8-tetrahydroquinolin-8-amine]RuCl2(triphenylphosphine); potassium <i>tert</i>-butylate In para-xylene at 117℃; for 24h; Inert atmosphere; | ||
57 %Chromat. | With potassium <i>tert</i>-butylate In diethyl ether at 45℃; for 144h; Reflux; Inert atmosphere; | |
Multi-step reaction with 2 steps 1: Aliquat 336; tert.-butylhydroperoxide / chlorobenzene / 3 h / 60 °C 2: caesium carbonate / N,N-dimethyl-formamide / 12 h / 20 °C | ||
Multi-step reaction with 3 steps 1: tert.-butylhydroperoxide; tetrabutylammomium bromide 2: Aliquat 336; tert.-butylhydroperoxide / chlorobenzene / 2 h / 40 °C 3: caesium carbonate / N,N-dimethyl-formamide / 12 h / 20 °C | ||
67 %Spectr. | With ruthenium(bis[2‐(ethylsulfanyl)ethyl]amine)(dichloro)(triphenylphosphine); potassium <i>tert</i>-butylate In toluene at 110℃; for 24h; Inert atmosphere; | |
Multi-step reaction with 2 steps 1: oxygen / 12 h / 120 °C / Green chemistry 2: dicyclohexyl-carbodiimide; dmap / 8 h / 20 °C / Inert atmosphere; Green chemistry | ||
Multi-step reaction with 2 steps 1: oxygen / 6 h / 120 °C 2: dicyclohexyl-carbodiimide; dmap / 8 h / 20 °C / Inert atmosphere; Green chemistry | ||
45 %Chromat. | With potassium <i>tert</i>-butylate; 1,3-dicyclohexyl-1H-imidazol-3-ium chloride; 1,2-bis-(diphenylphosphino)ethane; molybdenum hexacarbonyl In 1,3,5-trimethyl-benzene at 164℃; for 60h; Molecular sieve; Inert atmosphere; | |
With [Ru((PPh2CH2(C6H3N)CH2N=PCy3))ClH(PPh3)]; potassium hexamethylsilazane In toluene at 115℃; for 24h; Inert atmosphere; Schlenk technique; Glovebox; | ||
Multi-step reaction with 2 steps 1: acetic acid; hydrogen bromide; 1,2-diphenyl-1,1,2,2-tetrahydroperoxyethane / water / 0.33 h / 40 °C 2: acetic acid; hydrogen bromide; 1,2-diphenyl-1,1,2,2-tetrahydroperoxyethane / water / 6 h / 20 °C | ||
With oxygen at 120℃; for 2.5h; | ||
88 %Chromat. | With C22H30ClN4OPRu; potassium <i>tert</i>-butylate In toluene at 110℃; for 72h; Inert atmosphere; | |
78 %Chromat. | With 1-butyl-3-methylimidazolium molybdate at 110℃; for 48h; | |
Multi-step reaction with 2 steps 1: cobalt(II) acetate; oxygen; N-hydroxyphthalimide / 5 h / 90 °C 2: cobalt(II) acetate; oxygen; N-hydroxyphthalimide / 5 h / 90 °C | ||
94 %Chromat. | With Hoveyda-Grubbs catalyst second generation; potassium <i>tert</i>-butylate; tricyclohexylphosphine In toluene at 110℃; Inert atmosphere; Schlenk technique; | |
70 %Spectr. | With cis-[Ru(H)22(2-PPh2-3-Me-6-SiMe3-PC5H2)] In 5,5-dimethyl-1,3-cyclohexadiene at 140℃; for 140h; Inert atmosphere; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With iron orthoborate; In neat (no solvent); at 110℃; for 10h; | The oxidation reaction was performed in a magnetically stirredthree-neck flask equipped with thermometer and reflux condenser. The reaction in the flask was charged with benzyl alcohol (10 mL) and a prescribed amount of catalyst (0.5 g)was added so that the conversion of benzyl alcohol increased regularly with the amount of the catalyst until BzOH/Fe3BO6ratio at 165 C. The system was heated at a prescribed temperature (25-150 C) for a period of 10 h. At higher loadings no furtherincrease in the conversion was noticed. While conversion remained almost constant, the decrease in the selectivity for benzaldehyde was correlated with the increase in the selectivitiesof second generation products (dibenzyl ether and benzaldehyde )from benzaldehyde. Best performance was achievedfor a reaction period of 4-5 h. Benzyl alcohol conversion increased while selectivity for benzaldehyde decreased during the longer reaction time (Fig. 6). | |
With oxygen; In toluene; at 150℃; under 7500.75 Torr;Autoclave; | General procedure: Typically, CQ/SiO2 or organic quinone (EQ, BQ, DAQ, CQ or SQ)compound was added into 30 mL autoclave together with 2 g of alcohol and 1 g of toluene as a solvent or 1 g of DMSO with 0.3 g of water havebeen used as a solvent for SQ. The reactor was sealed and pressurizedwith O2 and heated to appropriate temperature for 1?24 h undercontinuous stirring. The products of reaction have been filtered afterreaction and analyzed by GC with HP-5 column using biphenyl as internalstandard. The products have been identified by comparison oftheir residence time with individual compounds and GC-MS analysis.The stability of the grafted catalyst has been tested for 3 times byfiltering of the catalyst after each cycle with subsequent addition to thefresh alcohol mixture for the next test as described in oxidation of cyclohexanol.Reaction products after filtering were quantitatively analyzedby GC and GC-MS with biphenyl as the internal standard. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 95.7% 2: 4.3% | With pyridine; 4-acetylamino-2,2,6,6-tetramethylpiperidine-N-oxyl; iodine; sodium hydrogencarbonate In dichloromethane; water at 20 - 25℃; for 1h; | Oxidation of alcohols with the 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxyl-iodine system. General procedure: A mixture of 10 mL of 0.1 mol/L solution of sodium hydrocarbonate and 0.084 g (0.4 mmol) of compound 1 were charged into a 50 mL flat-bottom flask equipped with a reflux condenser and a magnetic stirrer. 4 mmol of an alcohol dissolved in 10 mL of methylene chloride (alcohol-nitroxyl 1 molar ratio1 : 0.1) was added to the solution, and then 0.4 mmolof an amine was introduced (alcohol-amine 1 : 0.1; 1-amine 1 : 1). 2.0 g (8 mmol) of crystalline iodine was added at vigorous stirring to the two-phase system; the mixture was stirred during 3 h at 20-25° and then treated with 20% solution of sodium thiosulfate for elimination of excess iodine. Aqueous and organic layers were separated, and the product was additionally extracted from the aqueous layer with methylene chloride (2×10 mL). The organic phases were combined and analyzed by means of chromatography. |
1: 14% 2: 86% | With oxygen; caesium carbonate In toluene at 25℃; for 9h; | |
1: 86% 2: 14% | With Oxone; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; tetrabutylammomium bromide In toluene at 110℃; for 48h; Sealed tube; |
1: 86% 2: 14% | With Oxone; Pyridine-2,6-dicarboxylic acid; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; tetrabutylammomium bromide; iron(II) acetate In toluene at 110℃; for 48h; Sealed tube; | |
85% | With tert.-butylhydroperoxide In water at 94℃; for 0.5h; | |
1: 83% 2: 17% | With oxygen; potassium carbonate In toluene at 110℃; for 15h; | |
1: 78% 2: 10% | With di-tert-butyl peroxide In dimethyl sulfoxide at 100℃; for 2.5h; | |
1: 77% 2: 19% | With di-tert-butyl peroxide at 100℃; for 2.5h; | |
1: 73% 2: 10% | With bis-triphenylphosphine-palladium(II) chloride; 1,4-bromoiodobenzene; potassium carbonate In tetrahydrofuran at 65 - 70℃; for 20h; Inert atmosphere; Schlenk technique; | |
1: 20% 2: 68% | With (1,3-bis-(di-tert-butylphosphinito)cyclohexane)Ir=Cl at 190℃; for 16h; Schlenk technique; | |
1: 66% 2: 26% | With oxygen; potassium carbonate In water at 160℃; for 4h; Sealed tube; | 2.3. Catalytic experiments General procedure: The liquid phase oxidation was carried out in an ACE pressure tube filled with oxygen. Water suspension of Au NPs-rGO composites (8.1 mg in 2 mL), benzyl alcohol (1 mmol) and K2CO3 (3 mmol) were placed in a glass ACE pressure tube (10 mL) with a magnetic stirrer bar. The tube was sealed with a rubber O-ring and threaded Teflon seal under O2, and the entire mixture was vigorously stirred at 130 °C (bath temperature) for 4 h. The reaction mixture was cooled to room temperature and the organic product was extracted with ethyl acetate (3 × 10 mL). The aqueous phase was separated and could be used consecutively for another three times for the oxidation of benzyl alcohols (1st recycle 73%, 2nd recycle 74% and 3rd recycle 70% benzaldehyde was obtained). The upper organic phase was dried and concentrated under reduced pressure. The product was purified by column chromatography. |
1: 55% 2: 13% | With C59H105N3Os2P4 In toluene at 100℃; for 24h; Inert atmosphere; Schlenk technique; | |
1: 47% 2: 13% | With C59H105N3Os2P4 In toluene at 100℃; for 24h; Inert atmosphere; Schlenk technique; | |
12% | With caesium carbonate In para-xylene for 24h; Reflux; | |
1: 94 % Chromat. 2: 6 % Chromat. | With 2,4,6-trimethylphenyl bromide; potassium carbonate; triphenylphosphine In 1,2-dimethoxyethane at 85℃; for 12h; | |
1: 92.1 % Chromat. 2: 1 % Chromat. | With potassium hydroxide; [RuH(PNN)(CO)] In toluene at 115℃; for 4h; | |
76.6 % Turnov. | With oxygen; potassium carbonate at 100℃; for 5h; | |
In para-xylene at 130℃; for 10h; | ||
With hydrotalcite supported Cu nanoparticles In para-xylene at 130℃; for 13h; Inert atmosphere; | ||
With oxygen; potassium carbonate In toluene at 100℃; for 6h; | ||
With cesium bicarbonate; oxygen; copper dichloride In toluene at 40℃; for 12h; | ||
With ruthenium trichloride; nitrobenzene at 150℃; for 16h; Inert atmosphere; | ||
1: 69 %Chromat. 2: 10 %Chromat. | With silver tetrafluoroborate; oxygen; palladium diacetate; potassium carbonate; 1,2-bis[di(t-butyl)phosphinomethyl]benzene In toluene at 90 - 100℃; | |
With tert.-butylhydroperoxide In acetonitrile at 80℃; | ||
With oxygen In toluene at 60℃; for 6h; | ||
1: 32 %Chromat. 2: 31 %Chromat. | With Au/CeO2 In toluene at 110℃; for 22h; | |
1: 18 %Spectr. 2: 6 %Spectr. | With ozone Neat (no solvent); | |
Multi-step reaction with 2 steps 1: thionyl chloride; pyridine / dichloromethane 2: dimethylsulfoxide-d6 / 35 °C / Irradiation | ||
50 %Chromat. | With HRu(1,3-bis(6'-methyl-2'-pyridylimino)isoindolate)(PPh<SUB>3</SUB>)<SUB>2</SUB> In toluene for 24h; Inert atmosphere; Schlenk technique; Reflux; chemoselective reaction; | |
1: 9 %Chromat. 2: 85 %Chromat. | With copper(l) iodide; di-tert-butyl peroxide; (E)-N-((Z)-4-((2,6-dimethylphenyl)amino)pent-3-en-2-ylidene)-2,6-dimethylaniline In benzene at 90℃; for 6h; Sealed tube; Inert atmosphere; | |
1: 65 %Chromat. 2: 8 %Chromat. | With di-tert-butyl peroxide; copper diacetate; (E)-N-((Z)-4-((2,6-dimethylphenyl)amino)pent-3-en-2-ylidene)-2,6-dimethylaniline at 90℃; for 6h; Sealed tube; Inert atmosphere; | |
With bis[dichloro-(1,5-cyclooctadiene)ruthenium(2+)]; 1-butyl-3-methylimidazolium chloride; potassium hydroxide at 240℃; for 20h; | 3 A 250 ml three-neck flask equipped with a water separator and a thermometer was charged with 0.21 g of [Ru(1,5-cyclooctadiene)Cl2]2, 0.7 g of 1-methyl-3-n-butylimidazolium chloride, 5 g of potassium hydroxide and 100 g of benzyl alcohol. The mixture was heated under reflux for 20 h with stirring (magnetic stirrer) at atmospheric pressure and an oil bath temperature of 240° C. After the end of the reaction, 10.4% of unreacted starting material, 4.7% of benzaldehyde (intermediate of the reaction) and 67.4% of the carboxylic acid ester (benzyl benzoate; conversion determined by GC area %) were present in the reaction mixture. The reaction discharge can be worked up as described in example 1. | |
With gold supported on zirconium oxide; oxygen; caesium carbonate In Petroleum ether at 25℃; for 12h; | ||
With potassium carbonate In toluene at 85 - 90℃; for 5.5h; Schlenk technique; Inert atmosphere; Sonication; Green chemistry; | ||
With Pd/TiO2(at)MIL-101 at 90℃; for 24h; Inert atmosphere; | ||
With [Rh(PPh3)(trop2NH)][trifluoromethanesulfonate]; potassium <i>tert</i>-butylate; dinitrogen monoxide In tetrahydrofuran at -78 - 50℃; Molecular sieve; Schlenk technique; | ||
With [Rh(1,3,4,5-tetramethylimidazole-2-ylidene)(trop2NH)][trifluoromethanesulfonate]; potassium <i>tert</i>-butylate; dinitrogen monoxide In tetrahydrofuran; toluene at -78 - 50℃; Molecular sieve; Schlenk technique; | ||
With oxygen; sodium hydroxide In cyclohexane at 100℃; for 1h; | ||
1: 53 %Spectr. 2: 15 %Spectr. | With [{Cu2(5-phenyl-2,8-bis(6′-bipyridinyl)-1,9,10-anthyridine)-(μ-ClO4)2}(PF6)2]; dihydrogen peroxide In N,N-dimethyl-formamide at 70℃; for 12h; | |
With ceria In para-xylene at 150℃; for 12h; chemoselective reaction; | ||
at 350℃; for 12h; | ||
With oxygen In water at 90℃; for 16h; | 2.4. Aerobic oxidation of benzyl alcohol catalyzed byxAu/PDVB-VI-n General procedure: Aerobic oxidation of benzyl alcohol catalyzed by xAu/PDVA-VI-n was performed in a 10 mL flask under atmospheric pressure. In a typical reaction, benzyl alcohol (12.9 L, 0.125 mmol), K2CO3(5.19 mg, 0.0375 mmol), water (2.5 mL) and the requisite amount of xAu/PDVB-VI-n were added into the flask, and then pure O2 was purged into the flask. The mixture was kept at 90 °C for 16 h at the stirring speed of 600 rpm. After the reaction, HCl was added intothe mixture to adjust the pH to the range of 3 ∼ 4, and then the mixture was extracted with ethyl acetate (1.5 mL) and centrifuged to remove the catalyst. The conversion of benzyl alcohol and the yields of products were determined by gas chromatography-mass spectrometer equipped with a HP-5ms column (GC-MS, 7890BGC System-5977MSD, Agilent Technologies). The products were identified by comparison with known authentic standards, and an external standard method was used for the qualitative analysis. | |
With potassium hydroxide at 178℃; for 60h; Inert atmosphere; | 2.7 Experimental procedures for alcohol dehydrogenative coupling reactions catalyzed by 1 in the absence of a base and with KOH 200mg of 1 (0.007mmol) was placed in a small round-bottom flask. 21mmol of alcohol was added. In the case of 1-hexanol, 400mg (0.014mmol) of 1 was added to 35mmol of alcohol. An applied vacuum degassed the mixture. The mixture was then heated with slow stirring under an inert atmosphere of argon. The reaction mixture was cooled to room temperature and the composite catalyst was separated by filtration. The resulting liquid product mixture was analyzed by GC-MS. Total alcohol conversion and reaction conditions for each alcohol used are summarized in Table1 . | |
77 %Chromat. | With C36H32Cl2N2O2P2Ru; potassium <i>tert</i>-butylate In toluene at 150℃; for 16h; Inert atmosphere; Schlenk technique; | |
1: 31 %Chromat. 2: 3 %Chromat. | With C38H61N5OsP2 In toluene at 100℃; for 24h; Schlenk technique; | |
1: 76 %Spectr. 2: 15 %Spectr. | With C44H51IrN9OsP In toluene at 100℃; for 18h; Schlenk technique; Overall yield = 91 %Spectr.; | |
With dihydrogen peroxide In water at 110℃; for 24h; Schlenk technique; Inert atmosphere; | ||
With oxygen; potassium carbonate In water at 50℃; for 10h; Sealed tube; Darkness; | Oxidation of benzyl alcohol The thermal-driven oxidation of benzyl alcohol was carried out in dark under O2 atmosphere by heating at 20-50 °C in an oil bath for 10 h with a magnetic stirring. Typically, 0.25 mmol of benzyl alcohol and 34.6 mg of K2CO3 were added into a pressure bottle, followed by the addition of aza-CMP/AuxPdy catalyst containing 10 μmol AuxPdy (based on ICP-MS measurements). DI water was added into the solution until the total volume of the mixture reached 3 mL. Subsequently, the mixture was flowed with 0.2 MPa O2 and sealed. Once the reaction was completed, the pressure in the reaction system was released, followed by the addition of 5 mL ethyl acetate (EA) to extract products. Finally, the resulting solution was analyzed by gas chromatography-mass spectrometry (GC-MS, 7890A and 5975C, Agilent). The light-driven reactions were performed at room temperature under light irradiation with different light intensity in the absence of external heat source (i.e., without oil bath). | |
With cerium(IV) oxide In para-xylene at 150℃; Sealed tube; | ||
With tert.-butylhydroperoxide; C8H3BrO4(2-)*Cu(2+)*H2O*C3H7NO*0.5C6H12N2 In water; N,N-dimethyl-formamide at 20℃; for 12h; | 2.5. Catalytic procedure General procedure: The oxidation of benzyl alcohol was carried out as follows: A mixture containing tert-butyl hydroperoxide (TBHP, 2.26 mmol), benzyl alcohol (1 mmol) and catalyst (0.063 mmol based on Cu) in solvent (1 mL) was prepared. TBHP (70% in H2O) was dried prior to use based on the procedure reported in the literature using CH2Cl2 [32]. The mixture was stirred for proper time either at room temperature or at 40 °C and then the oxidation products were analyzed by GC. | |
With tert.-butylhydroperoxide; C8H3BrO4(2-)*Cu(2+)*H2O*C3H7NO*0.5C6H12N2 In water; N,N-dimethyl-formamide at 20℃; for 4h; | 2.5. Catalytic procedure General procedure: The oxidation of benzyl alcohol was carried out as follows: A mixture containing tert-butyl hydroperoxide (TBHP, 2.26 mmol), benzyl alcohol (1 mmol) and catalyst (0.063 mmol based on Cu) in solvent (1 mL) was prepared. TBHP (70% in H2O) was dried prior to use based on the procedure reported in the literature using CH2Cl2 [32]. The mixture was stirred for proper time either at room temperature or at 40 °C and then the oxidation products were analyzed by GC. | |
With dichloro[N,N-(2,6-pyridinediyl-kN)dimethylidyne]bis[2-methyl-2-propanamine-kN](triphenylphosphine)ruthenium; potassium <i>tert</i>-butylate at 150℃; for 72h; | ||
With C13H14N4O3S4V(1-)*Cs(1+); dihydrogen peroxide In water; acetonitrile at 80℃; for 6h; | ||
1: 83 %Chromat. 2: 12 %Chromat. | With C22H30ClN4OPRu; potassium <i>tert</i>-butylate In neat (no solvent) at 160℃; for 48h; Inert atmosphere; | |
With potassium chloride; oxygen In aq. phosphate buffer; ethanol; water Electrolysis; | ||
With oxygen at 120℃; for 2.5h; | Catalytic reactions General procedure: The reactions were performed in a Fischer-Porter glassreactor of 100 mL at 2 bar of O2 and 100 °C, except whenmentioned. The catalyst (4.1 μmol of metal) and benzylalcohol (1 mL, 9.6 mmol) were added into the reactorand stirred for a specific time, which was specified ahead.At the ending of the reaction, the catalyst was recoveredusing a neodymium magnet by placing it on the reactorwall. For analytical analyses, 10 μL of the final solutionwas collected and added to 1 mL of CH2Cl2. The injectionin the gas chromatograph was performed by using 1 μL of the prepared solution. In the recycling experiments, thecatalyst was washed with 3 mL of CH2Cl2, dried in an ovenfor 1 h at 80 °C and reused. The tests with N2 were carriedout under the same reaction conditions of the tests with O2.To evaluate the effect of water in the oxidation reaction,0.5 mL of water was added to 1 mL of benzyl alcohol atthe beginning of the reaction. | |
13 %Chromat. | With Hoveyda-Grubbs catalyst second generation; potassium hydroxide In toluene at 110℃; for 48h; Schlenk technique; Inert atmosphere; | |
1: 75 %Chromat. 2: 10 %Chromat. | With [Ru(1,2-bis(diphenylphosphino)benzene )(CO)2Cl2]; potassium <i>tert</i>-butylate; acetone In toluene at 100℃; for 6h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With lithium hexamethyldisilazane In neat (no solvent) at 0 - 20℃; for 3h; | 2.2. General procedure for transesterification reactions General procedure: Ester (1 mmol) and alcohol (3 mmol) were added in a round bottom flask, followed by the addition of base LiHMDS (2 mmol) at 0 °C. The reaction was stirred at room temperature for about 3 h. The reaction was monitored by TLC. After completion of the reaction, ethyl acetate was added to the reaction mixture and washed with water three times. The ethyl acetate layer was evaporated on the rota evaporator, and the crude products were purified by column chromatography in pet ether. |
97.0 % Spectr. | In hexane at 39℃; for 168h; lipase from Pseudomonas fluorescens; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With 3-chloro-benzenecarboperoxoic acid for 24h; Ambient temperature; in CHCl3; | |
97% | With 3-chloro-benzenecarboperoxoic acid for 24h; Ambient temperature; | |
76% | With sodium hydrogencarbonate; 3-chloro-benzenecarboperoxoic acid In dichloromethane at 0℃; for 0.5h; |
65% | With oxygen; benzaldehyde In 1,2-dichloro-ethane at 30℃; for 18h; | 2.3 Catalytic B-V Oxidation General procedure: The catalytic oxidation of ketone was carried out in a roundbottomflask of 25 mL volume equipped with magnetic stirrer.In the typical experiment, the flask was charged withsubstrate (2 mmol), CuPcTs-Zn2Al-LDH (8.0 mg), dichloroethane(10 mL), benzaldehyde (5 mmol), naphthalene(inert internal standard, 0.3 mmol) and then the mixture wasstirred at room temperature. Dioxygen was bubbled throughthe solution (10 mL min-1). We sampled during the reactionand the products were analyzed by GC-FID and GC-MSanalysis. |
55% | With bismuth(lll) trifluoromethanesulfonate In dichloromethane at 20℃; for 8h; | |
34% | With Octanoic acid; dihydrogen peroxide; Lipase B from Candida antarctica, immobilised on Immobead 150, recombinant from yeast In water at 45℃; for 40h; Enzymatic reaction; | |
57 % Chromat. | With 3-chloro-benzenecarboperoxoic acid In 1,2-dichloro-ethane at 40℃; for 5h; with/without catalyst; | |
57 % Chromat. | With 3-chloro-benzenecarboperoxoic acid In 1,2-dichloro-ethane at 40℃; for 5h; | |
20 %Chromat. | With dibenzyl diselenide; dihydrogen peroxide In tetrahydrofuran; water for 24h; Reflux; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In acetonitrile at 50℃; for 0.833333h; | |
98% | With bismuth(lll) trifluoromethanesulfonate In acetonitrile for 0.5h; Heating; | |
95% | With tris(pentafluorophenyl)borate In neat (no solvent) at 20℃; for 0.166667h; Green chemistry; | Typical experimental procedure: General procedure: B(C6F5)3 (0.5 mol %) was added to a mixture of alcohol/phenol/thiophenol/amine (1 mmol) and acetic anhydride (1.2 mmol), and the reaction mixture was stirred at room temperature until the complete conversion of starting material (monitored by TLC). After completion of reaction, the reaction mixture was diluted with water (20 mL) and extracted with ethyl acetate (3 15 mL). The organic layer was washed with cold saturated sodium bicarbonate solution (2 20 mL) followed by brine. The organic layer was dried over MgSO4 and concentrated under reduced pressure and products were purified over silica gel column chromatography in ethylacetate/hexane. All compounds were characterized and confirmed by comparison of their spectral data and physical properties with reported literature. |
91% | With o-benzenedisulfonimide at 80℃; for 1h; | |
86% | With decamolybdodivanadogermanic acid nanoparticles at 24.84℃; for 0.466667h; Neat (no solvent); | |
80% | With magnesium(II) perchlorate at 80℃; for 0.5h; | |
80% | With polyvinylpolypyrrolidone supported triflic acid In neat (no solvent) at 20℃; for 0.666667h; Green chemistry; | General experimental procedure General procedure: To a mixture of substrate (1.0 mmol) and acetic anhydride (1.0 mmol), 0.008 g PVPP.OTf (3.4 mol%) was added. The mixture was stirred at room temperature for the time indicated in Tables 2, 3 and 4. The progress of the reaction was followed by TLC or GC for aliphatic alcohols. After completion of the reaction, ethyl acetate (2 9 10 cm3) was added, and the catalyst was separated by filtration. The filtrate was washed with an aqueous solution of NaHCO3 (10%, 2 9 10 cm3) and water (2 9 10 cm3) and dried with Na2SO4. The solvent was evaporated under reduced pressure to afford the expected product. |
78.5% | In neat (no solvent) at 85℃; for 0.75h; | |
76% | In neat (no solvent) at 20℃; for 0.666667h; Green chemistry; | |
71% | In acetonitrile for 15h; Heating; | |
With P(MeNCH2CH2)3N 1) CH3CN, 24 deg C, 5 min; 2) CH3CN, 0.16 h, 24 deg C; further solvents: pentane, benzene; Yield given. Multistep reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With triethylamine at 90℃; for 2h; Ionic liquid; | Esterification in IL or in Molecular Solvents The amount of 0.3 g of IL was weighed in a screw-capped 3-ml vial, equipped with a magnetic stirrer; thereafter, the carboxylic acid was added, and then the amine was introduced by a syringe (TEA=benzoic acid1.2:1.0). The mixture was magnetically stirred and heated to 90 C until a clear colorless liquid phase was obtained. Finally, benzyl chloride (BnCl=benzoic acid 1.1:1 molar ratio) was added by means a syringe to the homogenous mixture. At the end of reaction, after cooling to rt, water and ethyl ether were added to the reaction mixture, and the mixture was transferred as quantitatively as possible (rinsing with both water and ethyl ether were carried out) to a separatory funnel, where also t-butylbenzene was added, as internal standard. The organic phase was washed twice with water (10mL), twice with NaHCO3 solution, and twice with 3M HCl, and with water again until neutrality; it was thereafter dried over anhydrous Na2SO4 and analyzed by GLC. For reaction in traditional molecular solvents, the amount of 1 mmol of carboxylic acid was weighed in a screw-capped 5-ml vial, equipped with a magnetic stirrer, and then 3mL of solvent were added. Thereafter, the amine, in the chosen molar ratio, was introduced by a syringe. The homogeneous mixture was magnetically stirred and heated to 90 C. Finally, benzyl chloride (BnCl=carboxylic acid 1.1:1 molar ratio) was added by means a syringe to the homogenous mixture. Further elaboration was as described previously. |
99% | With triethylamine for 1h; Heating; Inert atmosphere; Ionic liquid; | |
90% | With caesium carbonate In acetonitrile for 0.5h; Heating; |
89% | With 1,1'-(hexane-1,6-diyl)bis(1,8-diazabicyclo[5.4.0]undec-7-enium) dichlorine In ethanol; water at 70℃; for 2h; Green chemistry; | 2.3 Typical Procedure forEsterification Reaction General procedure: Carboxylic acids (1.00 mmol), primary chloroalkanes(1.20mmol) and IL-1 (0.30mmol) were added respectivelyinto a two necked flask equipped with 6mL 50%aqueous ethanol solution under stirring, then raised the systemtemperature to 70°C for a needed time in water bath.The progress of the reaction was monitored using thin layer chromatography (TLC). When the reaction was over, thereactor was cooled down to room temperature. The mixturewas diluted with water (10mL) and extracted with ethylacetate (3 × 5mL), the extract was dried over anhydrousNa2SO4,filtered, and concentrated in a rotary evaporatorto collect target product. Meanwhile, the reborn catalystcould be applied in the next cycle was after removing thesolvent and dried at 80°C under vacuum for 6h. All theesterification products were further purified by column |
87% | With 3,3'-(2,2'-(hexane-1,6-diylbis(azanediyl))bis(2-oxoethane-2,1-diyl))bis(1-propyl-1H-benzo[d]imidazol-3-ium) chloride; triethylamine at 68℃; for 0.3h; | 2.4. Typical esterification procedure General procedure: The carboxylic acids (1.1 mmol), the alkyl/allyl/aryl halides(1.00 mmol), dicationic IL catalyst DBimIL-3b (0.05 mmol) and tri-ethylamine (1.25 mmol) were loaded in a two necked flask andthe mixture was stirred at 60 °C for particular time. Progress ofthe reactions was monitored by TLC as well as the developmentof a white solid (Et3NHX) in the reaction mixture was a useful indication of the reaction progress. After completion of reaction,the mixture was allowed to cool at RT. The reaction mass was extracted in ethyl acetate (2 × 10 mL). The extract was washed with distilled water (2 × 10 mL) and 10% NaHCO3(2 × 10 mL), dried(anhydrous Na2SO4) and then concentrated in a rotary evaporator. The obtained products were pure as characterized by NMR and mass spectrometry. The obtained yields varied from 55-91%(Table 2). After the reaction, white solid of IL along with Et3NHX (X = Cl/Br)was dissolved in THF and filtered to remove Et3NHX. THF wasremoved using rotavapour and finally IL was washed thoroughly with EtOAc (2 × 10 mL) and recycled after drying in a vacuum at 60 °C for 2 h. |
78% | With tetrabutylammomium bromide; potassium carbonate; potassium iodide In diethoxymethane at 80 - 85℃; for 6h; | |
With potassium fluoride; 1,3-dimethylimidazolinium methanesulfonate at 90℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With P(MeNCH2CH2)3N In tetrahydrofuran for 5.5h; Ambient temperature; | |
94% | With hexamethyltriamido-N-benzylimidophosphate In tetrahydrofuran at 20℃; for 14.5h; | |
93% | With N,N'-bismesityl-imidazol-2-ylidene In tetrahydrofuran at 20℃; for 0.0833333h; |
92% | With diethylzinc In hexane; toluene at 20℃; for 5h; | |
87% | With 1,2,4-Triazole; 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 20℃; | |
83% | With C30H42N2; potassium <i>tert</i>-butylate In tetrahydrofuran at 20℃; for 2h; Molecular sieve; | |
76% | With TBA7[γ-HGeW10O36] In acetonitrile at 39.84℃; for 0.0166667h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
at 180℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In toluene at 150℃; for 16h; | |
97% | With 1,3-bis(2,6-diisopropylphenyl)imidazolylium-2-carboxylate at 120℃; for 3h; Inert atmosphere; | |
97% | With 1,3-bis(2,6-diisopropylphenyl)imidazolylium-2-carboxylate at 120℃; for 3h; Inert atmosphere; Schlenk technique; | 1.1 Transesterification of ethyl benzoate with monohydric alcohol Catalyst 1 (0.5 mol%) was added to a mixture of ethyl benzoate(3.0 g, 20 mmol) and benzyl alcohol (3a, 5.5 g, 50 mmol) under argon atmosphere and magnetic stirring. The mixture was processed continuously for 3 h at 120 °C in an oil bath. The resulting mixture was cooled and purified by column chromatography using an ethyl acetate/hexane (V/V = 20:1) mixture to yield benzyl benzoate (4a, Scheme 5). 4a: colorless liquid. 1H NMR: 5.36 (s, 2H), 7.40-7.56 (m, 8H), 8.03 (d, J = 8.4 Hz,2H). 13C NMR: 66.7, 128.1, 128.2, 128.3, 128.6, 129.7, 130.1,132.9, 136.1, 166.4. |
92% | With C16H25N3O2S In n-heptane for 48h; Reflux; Molecular sieve; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With sodium t-butanolate In neat (no solvent) at 20℃; for 1h; Inert atmosphere; Schlenk technique; Green chemistry; | |
94% | With lithium hexamethyldisilazane In tetrahydrofuran; toluene at 23℃; for 15h; Inert atmosphere; chemoselective reaction; | |
93% | With indium (III) iodide at 110 - 120℃; for 9h; |
86% | With carbonylhydrido(tetrahydroborato)[bis(2-diphenylphosphinoethyl)-amino]ruthenium(II); potassium <i>tert</i>-butylate In toluene at 120℃; for 48h; Inert atmosphere; Schlenk technique; Reflux; Green chemistry; | 2.2. General procedure for synthesis of amides General procedure: A mixture of amine (6.0 mmol), ester (3.0 mmol) and Ru-MACHO (1% mol) in toluene (3.0 mL) was placed in a flask and replaced withnitrogen gas. Then, t-BuOK (20% mol) was added in the mixture in the nitrogen gas flowing. The mixture was heated by reflux under the nitrogen atmosphere. During this time, the nitrogen gas was passed through the Schlenk line allowing the hydrogen gas to evolve from the reaction to escape the reactor. After the 48 h, the solvent was evaporated and the crude product was purified by flash chromatography on silica-gel to give the desired amides in 55-98% yields. The structures of the obtained amide swere determined by FT-IR and 1HNMR. |
68% | With C18H15IMnN3O3; sodium t-butanolate In toluene at 140℃; for 18h; Inert atmosphere; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With carbonylhydrido(tetrahydroborato)[bis(2-diphenylphosphinoethyl)-amino]ruthenium(II); potassium <i>tert</i>-butylate In toluene at 120℃; for 48h; Inert atmosphere; Schlenk technique; Reflux; Green chemistry; | 2.2. General procedure for synthesis of amides General procedure: A mixture of amine (6.0 mmol), ester (3.0 mmol) and Ru-MACHO (1% mol) in toluene (3.0 mL) was placed in a flask and replaced withnitrogen gas. Then, t-BuOK (20% mol) was added in the mixture in the nitrogen gas flowing. The mixture was heated by reflux under the nitrogen atmosphere. During this time, the nitrogen gas was passed through the Schlenk line allowing the hydrogen gas to evolve from the reaction to escape the reactor. After the 48 h, the solvent was evaporated and the crude product was purified by flash chromatography on silica-gel to give the desired amides in 55-98% yields. The structures of the obtained amide swere determined by FT-IR and 1HNMR. |
90% | With indium (III) iodide at 110 - 120℃; for 7.5h; | |
59% | With zirconocene dichloride In toluene at 110℃; for 20h; | 2 4.1. General procedure General procedure: Carboxylic ester (5.0 mmol), amine (6.5 mmol), and Cp2ZrCl2 (146.7 mg, 0.5 mmol) were suspended in 1.2 mL of anhydrous toluene. The reaction was stirred at 110°C for 4-20 h. The solvent was then removed under reduced pressure. The crude product was purified on a Biotage Isolera One using a Biotage SNAP Ultra cartridge (12 g or 25 g, 10-60% EtOAc in n-heptane) to isolate the desired amide. |
55% | With C31H40MnN2O3P*C6H14O; potassium <i>tert</i>-butylate In toluene; 1,3,5-trimethyl-benzene at 110℃; for 48h; Schlenk technique; | |
With methylaluminoxane In toluene at 110℃; for 0.25h; Inert atmosphere; Microwave irradiation; | A mixture of ester (1 mmol) and amine (2 mmol)was placed in a MW vial under an argon atmosphere. A 10%solution of MAO in toluene (2 mL, 3 mmol) was then added, andthe mixture was irradiated and stirred for 15 min at 110 °C. Thesolution was then cooled to r.t. and diluted with MTBE. Theproducts were isolated in the same manner as in method A. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With 3-chloro-benzenecarboperoxoic acid; copper(ll) bromide In 1,4-dioxane at 70℃; for 3h; | III.Conversion of Alkoxyamides 1 to Esters 2. General Procedure B. General procedure: To a solution of m-CPBA(1.2 mmol) and CuBr2 (0.1 mmol) in dry 1,4-dioxane (10 mL) was addeddropwise a solution of compound 1 (1mmol). The reaction mixture was stirred at the designated temperature until theTLC indicated the consumption of the starting martial compound 1. After the reaction was completed,the reaction mixture was allowed to cool to room temperature, and EtOAc (20 mL)was added. The resulting mixture was washed with saturated aqueous Na2S2O3(10mL) and saturated aqueousNa2CO3 (10 mL). The organic layer was dried overanhydrous Na2SO4, filtered, and removed under reducedpressure. The residue was purified by flash column chromatography on silica gelto give the desired products. |
75% | With N-Bromosuccinimide In toluene at 60℃; for 1h; | |
73% | With tetra-(n-butyl)ammonium iodide In N,N-dimethyl-formamide at 85℃; for 1.5h; Electrolysis; |
72% | With iodine; sodium carbonate In acetonitrile for 5h; Reflux; | General procedure for conversion of N-alkoxyamides (1) to carboxylic esters (2) General procedure: Sodium bicarbonate (56 mg, 0.66 mmol) and iodine (195 mg, 0.77 mmol) were added to N-(benzyloxy)benzamide (50 mg, 0.22 mmol) in anhydrous MeCN (3 mL). The mixture was heated to reflux for 5 h. It was then allowed to cool to rt, diluted with H2O (10 mL) and then extracted with EtOAc (210 mL). The combined organic extract was was hedwith saturated aqueous solution of Na2S2O3 (25 mL), H2O (10 mL), brine (10 mL), and then dried (MgSO4). It was then filtered and the filtrate was concentrated under reduced pressure to leave a residue which was purified by column chromatography on silica gel (petroleum ether:ethyl acetate 98:02) to provide the benzyl benzoate (2a)[12] as a colorless viscous liquid (Yield: 34 mg, 72%). IR (neat): 3034, 2927, 1716, 1602 cm1. 1H NMR (400 MHz, CDCl3): d8.00 (1H, d, J 8 Hz), 7.46 (1H, m), 7.37-7.15 (7H,m), 5.28 (2H, s). 13C NMR (100 MHz, CDCl3) d166.5, 136.1, 133.1, 130.1, 129.7,128.6, 128.4, 128.3, 128.2, 66.7. |
Multi-step reaction with 2 steps 1: t-BuOCl / CH2Cl2 / 20 °C 2: 93 percent / aq. NaN3 / acetonitrile / 0.08 h / 20 °C | ||
Multi-step reaction with 2 steps 1: 2.3 g / t-butylhypochlorite / benzene / 2 h / in the dark 2: 78 percent / silver carbonate / diethyl ether; trifluoroacetic acid / Ambient temperature | ||
Multi-step reaction with 2 steps 1: tetrabutylammonium acetate / acetonitrile; methanol / 4 h / 20 °C / Electrochemical reaction 2: 1,2-dichloro-ethane / 2 h / 80 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With caesium carbonate; 1,3-bis(mesityl)imidazolium chloride In dimethyl sulfoxide at 20℃; for 24h; | 5 Example 5 Add 0.4 mmol to the 10 mL round bottom flask with a magnetic stir bar.Benzyl chloride, 0.06 mmol of 1, 3-bis(2,4,6-trimethylphenyl)imidazolium chloride and 0.4 mmol of cesium carbonate,Then 2 mL of dimethyl sulfoxide was added as a solvent.The reaction was stirred at room temperature for about 24 hours in an air atmosphere.TLC testing,After the conversion of the arylbenzyl halide was completed, 8 mL of water was added.The mixture was transferred to a 50 mL separatory funnel.Extract 3 times with 5 mL of ethyl acetate.The combined organic phases were dried over Na 2 SO 4 .Dry for 30 min, remove Na2SO4 by filtration,After concentration, it was separated with a silica gel column (petrole ether: ethyl acetate = 10:1) to afford pure benzyl benzoate. |
Multi-step reaction with 3 steps 1: 10 g / sodium carbonate / methanol; H2O / 1) room temperature, 2) reflux, 2 h 2: 2.3 g / t-butylhypochlorite / benzene / 2 h / in the dark 3: 78 percent / silver carbonate / diethyl ether; trifluoroacetic acid / Ambient temperature | ||
Multi-step reaction with 2 steps 1: Aliquat 336; potassium carbonate; tert.-butylhydroperoxide / chlorobenzene / 3 h / 120 °C 2: caesium carbonate / N,N-dimethyl-formamide / 12 h / 20 °C |
Multi-step reaction with 3 steps 1: tert.-butylhydroperoxide; tetrabutylammomium bromide 2: Aliquat 336; tert.-butylhydroperoxide / chlorobenzene / 2 h / 40 °C 3: caesium carbonate / N,N-dimethyl-formamide / 12 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 87% 2: 7% | With C32H38Cl2N2P2Ru; potassium methanolate; hydrogen In tetrahydrofuran at 100℃; for 5h; Glovebox; Autoclave; | 23-26; 32; 34-36 Example 26: Hydrogenation of methyl benzoate catalyzed by ruthenium complex Ia-h General procedure: In a glove box, add a ruthenium complex Ia-g (0.001 mmol) or Ih (0.005 mmol),Potassium methoxide (175 mg, 2.5 mmol), tetrahydrofuran (20 mL), methyl benzoate (6.80 g, 50 mmol).After sealing the autoclave, take it out of the glove box and fill it with 50atm of hydrogen.The reaction kettle was heated and stirred in an oil bath at 100 ° C for 5 hours.After the reaction kettle was cooled in an ice-water bath for 1.5 hours, the excess hydrogen was slowly released.Use n-tridecane as internal standard, and use gas chromatography (using standard curve method, that is, tridecane as internal standard, methyl p-benzoate, benzyl alcohol, benzyl benzoate, and (The peak area ratio of trioxane is used as a standard curve, and the mass of methyl benzoate, benzyl alcohol, and benzyl benzoate contained in the reaction system mixture after the reaction is determined by measuring the ratio of the peak area in the reaction system)The conversion of methyl benzoate and the yield of benzyl alcohol and benzyl benzoate were determined. The results are shown in Table 4. |
1: 7% 2: 74% | With dichloro(benzene)ruthenium(II) dimer; 2-((di-p-tolylphosphino)methyl)-1-methyl-1H-imidazole; potassium <i>tert</i>-butylate; hydrogen In tetrahydrofuran at 100℃; for 2h; | |
1: 23% 2: 17% | With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; 2-((di-p-tolylphosphino)methyl)-1-methyl-1H-imidazole; potassium <i>tert</i>-butylate; hydrogen In tetrahydrofuran at 80℃; for 4.5h; |
With hydrogen; sodium methylate In various solvent(s) at 100℃; for 1h; Title compound not separated from byproducts.; | ||
With hydrogen; sodium hexamethyldisilazane In tetrahydrofuran at 100℃; for 1h; Title compound not separated from byproducts.; | ||
1: 24 %Chromat. 2: 10 %Chromat. | With hydrogen; potassium hydroxide In tetrahydrofuran at 100℃; for 16h; Autoclave; | 2 Example 2; Into a 100 mL autoclave equipped with a glass cylinder, 23 mg of the reddish purple powder obtained from Example 1, 24 mg of potassium hydroxide, 200 mg of methyl benzoate and 10 g of tetrahydrofuran were charged. The inside of the autoclave was replaced with nitrogen and then replaced with hydrogen, followed by increasing the hydrogen pressure to 1.0 MPa. Then, upon increasing the temperature to 100° C., the inner pressure became 1.3 MPa. Upon stirring the contents of the autoclave at 100° C. for 16 hours, the inner pressure became 1.2 MPa. When the contents of the autoclave were cooled to room temperature and analyzed by gas chromatography (internal standard method), the yield of benzyl alcohol was 24%. Also, methyl benzoate recovery was 50%. Besides, benzyl benzoate, which was supposed to be produced from benzyl alcohol and methyl benzoate, was produced as a by-product in 10%. |
With [RuCl2(PPh3){PyCH2NHC2H4PPh2}]; potassium methanolate; hydrogen In tetrahydrofuran at 40℃; for 3h; Glovebox; Inert atmosphere; | ||
1: 44 %Chromat. 2: Ca. 8 %Chromat. | With [RuCl2(2-(diphenylphosphino)-N-((6-((diphenylphosphino)methyl)pyridin-2-yl)methyl)ethan-1-amine)]; hydrogen; sodium methylate In dichloromethane at 80℃; for 2h; Autoclave; | |
With potassium <i>tert</i>-butylate; hydrogen In tetrahydrofuran at 80℃; for 24h; | ||
1: 63 %Chromat. 2: 10 %Chromat. | With C48H43ClN2P2Ru; potassium <i>tert</i>-butylate; hydrogen In 2-methyltetrahydrofuran; <i>tert</i>-butyl alcohol at 50℃; for 16h; Inert atmosphere; | 27 Example 27 Reduction of Me-benzoate (44) with hydrogen. A 10 mL glass tube was charged with complex (0.01 mmol, S/C 500/1 ), loaded in a Biotage Endevaour, purged with nitrogen five times by pressurizing to 2 bar and releasing pressure. Methyl benzoate (5 mmol, 0.63 mL), 1 M KOfBu solution in t-BuOH (0.5 mL) and solvent (4.37 mL) were injected. The vessel was purged again with nitrogen three times, five times under stirring and a further five time with hydrogen (by pressurizing to 28 bar and releasing pressure). The pressure was set at 28 bar of hydrogen and the reaction was stirred (600 rpm) at 50 C for 16 hours. After cooling to room temperature the pressure was released and the reaction was sampled (2mL MeOH and 0.5 mL water were added). An aliquot of 100 μ was diluted in 1 mL acetonitrile and analyzed by GC (Table 6). Table 6. Catalytic hydrogenation of Me-benzoate (44) with complex 14(0.2 mol%) in the presence of KOfBu at 50 °C with H2 (28 bar) in different solvents. Complex Solvent / Conversion Benzyl Benzyl Others 10% tBuOH (%) Alcohol (%) benzoate (%) [A] (%) 1 14 MeTHF 75 63 10 2 2 14 Toluene 55 33 14 8 [Al Benzylbenzoate is the benzyl alcohol ester of benzoic acid and it formation requires the conversion of methyl benzoate by hydrogenation. The pincer complex 14 catalyses the ester hydrogenation. |
With C18H30ClIrN2OS; hydrogen; sodium methylate In tetrahydrofuran at 40℃; for 24h; Autoclave; Overall yield = 11 %Chromat.; chemoselective reaction; | ||
1: 68 %Chromat. 2: 7 %Chromat. | With C17H16BrMnNO3P; potassium <i>tert</i>-butylate; hydrogen In tetrahydrofuran at 80 - 120℃; for 40h; Autoclave; | |
Multi-step reaction with 2 steps 1: C17H16BrMnNO3P; hydrogen / tetrahydrofuran / 3 h / 100 °C / 37503.8 Torr / Autoclave 2: C17H16BrMnNO3P; potassium <i>tert</i>-butylate; hydrogen / 1,4-dioxane / 3 h / 100 °C / 37503.8 Torr / Autoclave | ||
Multi-step reaction with 2 steps 1: tetrahydrofuran / 3 h / 100 °C / Inert atmosphere; Autoclave 2: C17H16BrMnNO3P; potassium <i>tert</i>-butylate; hydrogen / 1,4-dioxane / 3 h / 100 °C / 37503.8 Torr / Autoclave | ||
Multi-step reaction with 2 steps 1: tetrahydrofuran / 3 h / 80 - 120 °C / Inert atmosphere; Autoclave 2: C17H16BrMnNO3P; potassium <i>tert</i>-butylate; hydrogen / 1,4-dioxane / 3 h / 100 °C / 37503.8 Torr / Autoclave | ||
1: 46 %Chromat. 2: 12 %Chromat. | With dichlorido-bis[(2-diisopropylphosphino)ethyl]amine-cobalt(II); hydrogen; sodium methylate In 1,4-dioxane at 140℃; for 48h; Autoclave; | |
1: 61 %Chromat. 2: 7 %Chromat. | With C33H30N2Ru; hydrogen In tetrahydrofuran at 65℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen; sodium methylate at 100℃; for 1h; Title compound not separated from byproducts.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With cesium phosphate; N-benzyl-N,N,N-triethylammonium chloride In toluene for 45h; Reflux; | |
85% | With lithium hexamethyldisilazane In neat (no solvent) at 0 - 20℃; for 3h; | 2.2. General procedure for transesterification reactions General procedure: Ester (1 mmol) and alcohol (3 mmol) were added in a round bottom flask, followed by the addition of base LiHMDS (2 mmol) at 0 °C. The reaction was stirred at room temperature for about 3 h. The reaction was monitored by TLC. After completion of the reaction, ethyl acetate was added to the reaction mixture and washed with water three times. The ethyl acetate layer was evaporated on the rota evaporator, and the crude products were purified by column chromatography in pet ether. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With cesium phosphate; N-benzyl-N,N,N-triethylammonium chloride for 1h; Reflux; | |
86% | With lithium hexamethyldisilazane In neat (no solvent) at 0 - 20℃; for 3h; | 2.2. General procedure for transesterification reactions General procedure: Ester (1 mmol) and alcohol (3 mmol) were added in a round bottom flask, followed by the addition of base LiHMDS (2 mmol) at 0 °C. The reaction was stirred at room temperature for about 3 h. The reaction was monitored by TLC. After completion of the reaction, ethyl acetate was added to the reaction mixture and washed with water three times. The ethyl acetate layer was evaporated on the rota evaporator, and the crude products were purified by column chromatography in pet ether. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With potassium phosphate; N-benzyl-N,N,N-triethylammonium chloride for 7.5h; Reflux; | |
75% | With diethylamine; lithium bromide at 58℃; for 24h; neat (no solvent); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With lithium bromide at 20℃; | |
89% | With Merrifield resin-supported N3=P(MeNCH2CH2)3N In tetrahydrofuran at 23 - 25℃; Inert atmosphere; | General procedure for room-temperature transesterifications and amidations General procedure: A round bottom centrifuge tube containing catalyst 4 (6.7 mol % based on the percent phosphorus determined by elemental analysis or as otherwise stated in the footnotes of the corresponding Tables) was equipped with a rubber septum and two magnetic stir bars for extra stirring efficiency. After flushing the tube with argon, it was charged via syringe with a higher ester (5 mmol) and MeOH (5 mL) for transesterifications. For amidations, the tube was similarly charged with an ester (2 mmol), amino alcohol (2 mmol), and THF (3 mL). The reaction mixture was vigorously stirred at room temperature (23-25 °C) and progress of the reaction was monitored by thin layer chromatography. Upon completion of the reaction, the reaction mixture was filtered through Whatman No. 1 filter paper and washed with 3 × 10 mL of THF. The combined organics were subjected to short-path silica gel chromatography (0-20% ethyl acetate in hexanes v/v) to obtain an analytically pure product. In the case of amides, products were purified using a short-path silica gel column eluted with dichloromethane/methanol (95:5, v/v). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | Stage #1: benzaldehyde With 1-n-butyl-3-methyl-2,3-dihydro-imidazol-2-ylidene for 0.166667h; Stage #2: benzyl bromide With oxygen at 60℃; for 13h; | |
63% | Stage #1: benzaldehyde With 18-crown-6 ether; oxygen; 3,4-dimethylthiazolinium iodide; potassium carbonate In acetonitrile at 20℃; for 0.5h; Stage #2: benzyl bromide In acetonitrile at 20℃; | 4.2. Typical procedure for synthesis of product 4 General procedure: To a flame-dried 25 mL two-neck flask under positive oxygen pressure were added aldehyde 1 (0.2 mmol), thiazolium salt 3 (0.2 mmol), K2CO3 (0.44 mmol), 18-crown-6 (0.132 mmol), and anhydrous oxygen-saturated CH3CN (2 mL). The resulting mixture was stirred at room temperature for 30 min, followed by addition of benzyl halide 2 (0.4 mmol) in 2 mL of CH3CN with a funnel. After completion of the reaction (monitored by TLC), the reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by PTLC (ethyl acetate/petroleum ether=1/40) to give 4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | In dichloromethane; at 20℃; for 14h; | General procedure: At room temperature, organic carbonyl acid 3 (R-COOH, 0.5 mmol) was added into a reaction tube equipped with a small magnet. Then a solution of tertiary amine 1 (R1CH2-NR2R3, 0.5 mmol ) in DCM (2.5 mL) was added dropwise in 2 min. After the mixture was stirred at room temperature for a few minutes, 1 equivalents of dimethyl acetylenedicarboxylate (DMAD, 2) was added. The reaction was stirred overnight at room temperature, and then monitored by TLC with silica gel coated plates. After being stirred for 14 h, the solvent was removed and the residue was purified by a flash column chromatography with silica gel with ethyl acetate/hexane (1:25-30) as eluent to give the desired products 4, 5, and 7. Most of compounds are known and confirmed by NMR, ESI-MS, IR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With oxygen In neat (no solvent) at 120℃; Autoclave; | ||
With oxygen In neat (no solvent) at 120℃; for 4h; | 2.3. Catalytic performance tests The solvent-free selective oxidation of benzyl alcohol was performedunder atmosphere pressure. 100 mg catalyst was dispersedin 5 ml benzyl alcohol in a three-necked batch reactor with a refluxcondenser under stirring. The suspension was kept at 393 K withoxygen bubbled in at a flow-rate 20 ml/min. After the reaction,the catalyst was separated from the solution by centrifugationand the products were analyzed and identified by gas chromatography(GC, Agilent Technologies 7890B with a 0.32 mm x 30 m HP-5 capillary column, He carrier). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydride In toluene; mineral oil at 110℃; for 48h; Inert atmosphere; | Reaction procedure with the supported Ag NPs General procedure: Prior to use, the catalyst (162 mg; 3 mol%) was dried at 150°C. Then, NaH (60% dispersionin mineral oil; 12 mg) and 1 ml of toluene were added, followed by 1 h heating at 110C. 1.8 mmol of 4-ethylaniline (220 l) and 3.6 mmol benzyl alcohol (380 l) were added. After 26 h reaction at110°C, analysis was performed as in Section 2.2. To recycle the catalyst, the material was washed with water after reaction to remove inorganic impurities, followed by washing with 2-propanol (2×)and acetone (2×). The material was dried overnight at 150°C after which again NaH (0.5 mmol; 12 mg) was added and a new run was started. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With triethylamine at 70℃; for 3h; | |
85% | With triethylamine at 130℃; for 24h; Autoclave; | General procedure for the alkoxycarbonylation reaction ofbromoarenes General procedure: A 25 mL glass lined autoclave was charged with bromoarene (4 mmol), triethylamine (8 mmol) and MNP-Im-NH2-Pd (0.02 mmol Pd in 5 mL dry alcohol). The autoclave was sealed, purged three times with carbon monoxide (CO), and pressurized to 500 psi with CO. The reaction mixture was stirred at 130 °C for 24 h. The autoclave was cooled to room temperature and CO was carefully released. The catalytic system was magnetically separated and the solution decanted and evaporated under vacuum in a rotary evaporator. The product was diluted with ether (20 mL), washed with aqueous hydrochloric acid (2× 10mL, 1N), dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The products were purified by column chromatography on silica gel (ethyl acetate:hexane 20:1 as an eluent solvent) to afford the desired products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With potassium <i>tert</i>-butylate In neat (no solvent) for 1h; Autoclave; | |
68% | With carbonylhydrido(tetrahydroborato)[bis(2-diphenylphosphinoethyl)-amino]ruthenium(II); potassium <i>tert</i>-butylate In toluene at 120℃; for 48h; Inert atmosphere; Schlenk technique; Reflux; Green chemistry; | 2.2. General procedure for synthesis of amides General procedure: A mixture of amine (6.0 mmol), ester (3.0 mmol) and Ru-MACHO (1% mol) in toluene (3.0 mL) was placed in a flask and replaced withnitrogen gas. Then, t-BuOK (20% mol) was added in the mixture in the nitrogen gas flowing. The mixture was heated by reflux under the nitrogen atmosphere. During this time, the nitrogen gas was passed through the Schlenk line allowing the hydrogen gas to evolve from the reaction to escape the reactor. After the 48 h, the solvent was evaporated and the crude product was purified by flash chromatography on silica-gel to give the desired amides in 55-98% yields. The structures of the obtained amide swere determined by FT-IR and 1HNMR. |
56% | With bromopentacarbonylmanganese(I); potassium <i>tert</i>-butylate; N,N-bis-(3-dimethylaminopropyl)amine In toluene at 90℃; Schlenk technique; Sealed tube; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With carbonylhydrido(tetrahydroborato)[bis(2-diphenylphosphinoethyl)-amino]ruthenium(II); potassium <i>tert</i>-butylate In toluene at 120℃; for 48h; Inert atmosphere; Schlenk technique; Reflux; Green chemistry; | 2.2. General procedure for synthesis of amides General procedure: A mixture of amine (6.0 mmol), ester (3.0 mmol) and Ru-MACHO (1% mol) in toluene (3.0 mL) was placed in a flask and replaced withnitrogen gas. Then, t-BuOK (20% mol) was added in the mixture in the nitrogen gas flowing. The mixture was heated by reflux under the nitrogen atmosphere. During this time, the nitrogen gas was passed through the Schlenk line allowing the hydrogen gas to evolve from the reaction to escape the reactor. After the 48 h, the solvent was evaporated and the crude product was purified by flash chromatography on silica-gel to give the desired amides in 55-98% yields. The structures of the obtained amide swere determined by FT-IR and 1HNMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With carbonylhydrido(tetrahydroborato)[bis(2-diphenylphosphinoethyl)-amino]ruthenium(II); potassium <i>tert</i>-butylate In toluene at 120℃; for 48h; Inert atmosphere; Schlenk technique; Reflux; Green chemistry; | 2.2. General procedure for synthesis of amides General procedure: A mixture of amine (6.0 mmol), ester (3.0 mmol) and Ru-MACHO (1% mol) in toluene (3.0 mL) was placed in a flask and replaced withnitrogen gas. Then, t-BuOK (20% mol) was added in the mixture in the nitrogen gas flowing. The mixture was heated by reflux under the nitrogen atmosphere. During this time, the nitrogen gas was passed through the Schlenk line allowing the hydrogen gas to evolve from the reaction to escape the reactor. After the 48 h, the solvent was evaporated and the crude product was purified by flash chromatography on silica-gel to give the desired amides in 55-98% yields. The structures of the obtained amide swere determined by FT-IR and 1HNMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With carbonylhydrido(tetrahydroborato)[bis(2-diphenylphosphinoethyl)-amino]ruthenium(II); potassium <i>tert</i>-butylate In toluene at 120℃; for 48h; Inert atmosphere; Schlenk technique; Reflux; Green chemistry; | 2.2. General procedure for synthesis of amides General procedure: A mixture of amine (6.0 mmol), ester (3.0 mmol) and Ru-MACHO (1% mol) in toluene (3.0 mL) was placed in a flask and replaced withnitrogen gas. Then, t-BuOK (20% mol) was added in the mixture in the nitrogen gas flowing. The mixture was heated by reflux under the nitrogen atmosphere. During this time, the nitrogen gas was passed through the Schlenk line allowing the hydrogen gas to evolve from the reaction to escape the reactor. After the 48 h, the solvent was evaporated and the crude product was purified by flash chromatography on silica-gel to give the desired amides in 55-98% yields. The structures of the obtained amide swere determined by FT-IR and 1HNMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With carbonylhydrido(tetrahydroborato)[bis(2-diphenylphosphinoethyl)-amino]ruthenium(II); potassium <i>tert</i>-butylate In toluene at 120℃; for 48h; Inert atmosphere; Schlenk technique; Reflux; Green chemistry; | 2.2. General procedure for synthesis of amides General procedure: A mixture of amine (6.0 mmol), ester (3.0 mmol) and Ru-MACHO (1% mol) in toluene (3.0 mL) was placed in a flask and replaced withnitrogen gas. Then, t-BuOK (20% mol) was added in the mixture in the nitrogen gas flowing. The mixture was heated by reflux under the nitrogen atmosphere. During this time, the nitrogen gas was passed through the Schlenk line allowing the hydrogen gas to evolve from the reaction to escape the reactor. After the 48 h, the solvent was evaporated and the crude product was purified by flash chromatography on silica-gel to give the desired amides in 55-98% yields. The structures of the obtained amide swere determined by FT-IR and 1HNMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | In N,N-dimethyl-formamide at 25℃; for 48h; Irradiation; Green chemistry; | |
96% | With C35H20F34NO3(1-)*Pd(2+)*Cl(1-); N-ethyl-N,N-diisopropylamine In neat (no solvent) at 130℃; for 0.333333h; Microwave irradiation; | 7 Alkoxycarbonylation of aryl halide and alcohol: general procedure General procedure: A mixture of the aryl halide (1.0 mmol), alcohol (5.0 equiv), Mo(CO)6 (0.5 equiv), DIPEA (1.5 equiv) and palladacycle 1 (1 mol % Pd) was heated in a pressure tube at 130 °C under microwave irradiation. The reaction was monitored by TLC. When the reaction has completed, the reaction mixture was cooled to room temperature and the alcohol was removed. The crude mixture was subjected to F-SPE to remove palladacycle 1 (see general procedure for the recycling of palladacycle 1) and the solution of crude product was concentrated, diluted with EtOAc (20 mL) and washed successively with 2 M HCl (210 mL) and water (10 mL). The organic layer was driedover anhydrous MgSO4, filtered and concentrated to give pure 6. |
91% | With potassium phosphate; palladium diacetate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene for 1.5h; Milling; |
82% | With tributyl-amine In N,N-dimethyl-formamide at 80℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With tert.-butylhydroperoxide; tetra-(n-butyl)ammonium iodide In decane; benzene at 20 - 90℃; for 12h; Schlenk technique; | (B) Typical experimental procedureGeneral experimental procedures for the TBAI-catalyzed synthesis ofcyclohex-2-enyl benzoate General procedure: An over-dried Schlenk tube was charged with tetrabutylammonium iodide (TBAI) (0.1 mmol),phenylglyoxylic acid (1a) (0.5 mmol) and cyclohexene (2a) (1.5 mmol) in benzene (2 mL) wasadded, Then tert-butyl hydroperoxide (1.25 mmol, 5~6 M in decane) was added dropwise into themixture at room temperature. The resulting mixture was stirred at 90 °C for 12 h. Then, the cooledreaction mixture was dissolved in water (5 mL) and extracted with CH2Cl2 (3×5 mL). Thecombined organic layer was dried with anhydrous MgSO4, and the product was further purified bysilica gel column chromatography and eluted with ethyl acetate and petroleum ether mixture toafford the product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48%Spectr.; 24%Spectr.; 27%Spectr.; 9%Spectr. | With C39H80N6Si6Th; In benzene-d6; at 20℃; for 36h;Sealed tube; | General procedure: A J. Young Teflon sealed NMR tube was loaded with a certain amount of precatalyst from a stock solution in C6D6. The respective aldehydes (50 equivalents) were added and immediately diluted to a total volume of 600muL with C6D6. The tube was sealed and taken out of the glovebox. The reaction progress was monitored by 1H NMR. The ratio between the ester and aldehyde was calculated by integration of the methylene signals and aldehyde signals. Then the tube was opened to the air, and the reaction was quenched with methanol and submitted to MS analysis. The 1H NMR of ester products from coupling of benzaldehyde with 2-pyridinylaldehyde [28], isobutyraldehyde [28], cyclohexyladehyde [28], 2-naphthaldehyde [28], 3-nitrobenzadehyde [27,59], were compared with previous reports. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 54.7 %Spectr. 2: 31.5 %Spectr. 3: 9.1 %Spectr. 4: 9 %Spectr. | With C48H69N3Th In benzene-d6 at 20℃; for 12h; Glovebox; Inert atmosphere; | |
1: 28.2 %Spectr. 2: 13.9 %Spectr. 3: 13.7 %Spectr. 4: 9.5 %Spectr. | With C48H69N3Th In benzene-d6 at 20℃; for 12h; Glovebox; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydroxylamine; 1,8-diazabicyclo[5.4.0]undec-7-ene In methanol; water at 20℃; for 3h; | Typical procedure General procedure: To a stirred solution of the methyl ester (1 equiv) in MeOH (4 volumes), was added DBU (3 equiv) and 50% v/v aqueous solution NH2OH(aq) (10 equiv) at 0° C to room temperature. The reaction mixture was stirredfor 20 min to 48 h (depending on the steric hindrance around the ester) and then purified directly by mass-triggered preparative LCMS Waters X-Terrareverse-phase column (C-18, 5 l silica, 19 mm diameter, 100 mm length, flowrate of 40 ml/min) and decreasingly polar mixtures of water (containing 0.1%formic acid) and acetonitrile as eluent. The fractions containing the desired compound were evaporated to dryness to afford the final compounds usuallyas a crystalline solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 46 %Spectr. 2: 28 %Spectr. 3: 11 %Spectr. 4: 15 %Spectr. | With C38H53N3Th In benzene-d6 for 1.5h; | |
1: 40 %Spectr. 2: 27 %Spectr. 3: 15 %Spectr. 4: 8 %Spectr. | With C39H80N6Si6Th In benzene-d6 at 20℃; for 36h; Sealed tube; | 2.13 General procedure for the crossed Tishchenko reactions General procedure: A J. Young Teflon sealed NMR tube was loaded with a certain amount of precatalyst from a stock solution in C6D6. The respective aldehydes (50 equivalents) were added and immediately diluted to a total volume of 600μL with C6D6. The tube was sealed and taken out of the glovebox. The reaction progress was monitored by 1H NMR. The ratio between the ester and aldehyde was calculated by integration of the methylene signals and aldehyde signals. Then the tube was opened to the air, and the reaction was quenched with methanol and submitted to MS analysis. The 1H NMR of ester products from coupling of benzaldehyde with 2-pyridinylaldehyde [28], isobutyraldehyde [28], cyclohexyladehyde [28], 2-naphthaldehyde [28], 3-nitrobenzadehyde [27,59], were compared with previous reports. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With caesium carbonate In dimethyl sulfoxide at 20℃; for 24h; Molecular sieve; | 23 Example Twenty-three: Preparation of aromatic ester compounds of the formula Iw The specific preparation method is: under air conditions,Add magnetons in a dry, clean 25 mL round bottom flask.N-Boc amide (93.3 mg, 0.3 mmol) of the formula IIa,An alcohol of the formula IIIf (52.3 mg, 0.45 mmol),Cs2CO3 (19.5 mg, 0.06 mmol),Then add 1.5 mL of DMSO dried in molecular sieves and react at room temperature for 24 h.The mixture was extracted with dichloromethane (25 mL×3×).The filtrate was rotary evaporated to remove the solvent. After concentration, the mixture was subjected to silica gel column chromatography (200-300 mesh) eluted with ethyl acetate and petroleum ether (1:30).The compound of the formula Iw was isolated in an amount of 54.3 mg, yield 85%.This product is a liquid. |
85% | With caesium carbonate In dimethyl sulfoxide at 23℃; for 12h; Schlenk technique; | |
80% | With potassium phosphate In tetrahydrofuran at 23℃; for 15h; Inert atmosphere; Schlenk technique; |
76% | With sodium t-butanolate In toluene at 150℃; for 24h; Sealed tube; | General procedure for NaOtBu-catalyzed esterification ofamides. General procedure: To a dry 35 mL sealed tube with a stir bar, amide (0.5 mmol), NaOtBu (0.1 mmol), phenol/alcohol (1.0 mmol) and toluene (5.0 mL) were added. After sealed with a Teflon-lined cap, the reaction mixture was stirred at 150 °C for 24 h. Then the mixture was cooled to room temperature and quenched with H2O (5.0 mL). The mixture was separated and extracted with ethyl acetate (EA) (15 mL×3). The combined organic layer was dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography with ethyl acetate/petroleum ether to give the desired product. More experimental details and characterizations are available in the Supporting Information online. |
75% | With cesium fluoride In acetonitrile at 100℃; for 15h; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | Stage #1: benzyl bromide With potassium carbonate; 1,4-dimethyl-1,2,4-triazolium iodide In acetonitrile at 40℃; for 1h; Schlenk technique; Inert atmosphere; Stage #2: In acetonitrile at 40℃; for 36h; Schlenk technique; | |
65% | With caesium carbonate; 1,3-bis(mesityl)imidazolium chloride In dimethyl sulfoxide at 20℃; for 24h; | 16 Example 16 0.4 mmol of benzyl bromide was sequentially added to a 10 mL round bottom flask equipped with a magnetic stir bar.0.06 mmol of 1, 3-bis(2,4,6-trimethylphenyl)imidazolium chloride and 0.4 mmol of cesium carbonate were added to 2 mL of dimethyl sulfoxide as a solvent.The reaction was stirred at room temperature for about 24 hours in an air atmosphere, and TLC was detected.After the conversion of the arylbenzyl halide was completed, 8 mL of water was added. The mixture was transferred to a 50 mL separatory funnel.It was extracted 3 times with 5 mL of ethyl acetate, and the combined organic phases were dried over Na2SO4.After drying for 30 min, the Na 2 SO 4 was removed by filtration, and then concentrated and then purified using silica gel column ( petroleum ether: ethyl acetate = 10:1) to afford pure benzyl benzoate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With Ac-Cys-OMe; bismuth(III) oxide; N-ethyl-N,N-diisopropylamine In dichloromethane at 24℃; Irradiation; | 6 Example 6: Synthesis of Compound 6a Iodide compound 6 (50 mg),Bismuth oxide (0.7mg, 1mol%),N-acetyl-L-cysteine methyl ester (7.9 mg, 0.3 equiv) was weighed into a 10 mL reaction tube.After deoxidation, the reaction solvent dichloromethane (1.5 ml) was added in order.And N,N-diisopropylethylamine (0.26 ml, 10 equiv),Reacted under 1W blue LED light,The reaction is terminated after the iodo compound 6 is consumed.Purification by column chromatography gave Compound 6a (31 mg). |
76% | With tetraethylammonium perchlorate; triethylamine In ethanol; dimethyl sulfoxide at 20℃; for 12h; Electrolysis; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With potassium carbonate In acetonitrile at 80℃; for 8h; | II. General synthetic procedure for the preparation of compounds (3a-u, 5a-i and 7a-g) General procedure: To a stirred solution of a pyridinium salt of phenacyl bromide (1 mmol) and thebenzylamine/benzyl alcohol/amine (1 mmol) was added in CH3CN and allowed to stir. K2CO3was added to the reaction mixture and refluxed for 8 h. The reaction progress was monitoredby using TLC. After complete consumption of the starting materials, the CH3CN wasevaporated under reduced pressure and the crude reaction mixture was diluted with EtOAc (35mL) and washed with water (10 mL) and brine (10 mL), then dried over anhydrous sodiumsulfate and concentrated to yield the crude amide, which was purified by using silica gel columnchromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With zinc(II) oxide; In neat (no solvent); at 0 - 20℃; for 2.5h;Green chemistry; | General procedure: In the mixture of cyclic/acyclic ether (11 mmol) and acid chloride (10 mmol), nano-ZnO (5 mol%) was added at 0-5 C and stirred at room temperature for an appropriate time. After the TLC monitoring reaction, the ZnO was removed by filtration and washed repeatedly with dichloromethane and water. It was then dried at 60 C for 3 h and used for the next catalytic cycle. The solution was extracted three times with dichloromethane and water, and dried on anhydrous Na2SO4. The product was purified on a silica gel column chromatography using a mixture of petroleum ether/ethyl acetate (150:1, v/v). The product is obtained by vacuum distillation to remove the solvent. The compounds were characterized by 1H NMR and 13C NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With caesium carbonate In tetrahydrofuran at 90℃; for 12h; Sealed tube; | A 5.0 mL vial equipped with a Teflon coated stir bar was charged with Cs2CO3 (391.0 mg, 1.2 mmol), 2a (0.45 mmol), 3a (0.45 mmol) followed by sequential addition of THF (3.0 mL). Next, thevial was sealed with a Teflon screw cap and removed from glovebox, and then, the mixture was allowed warm to 90 °C refluxed for an additional 12 h. After completion of the reaction, the mixture was filtered through a thin pad of celite. The filter cake was washed with ethyl acetate (3× 2.0 mL), then the combined filtrate was concentrated in vacuo to provide a crude reaction mixture that was purified by silica gel column chromatography to affored the product 9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75%; 71% | With tert.-butylhydroperoxide; tetra-(n-butyl)ammonium iodide; In water; acetonitrile; at 80℃; for 24h;Sealed tube; | General procedure: Under air atmosphere, a sealable reaction tube equipped with a magnetic stir bar and covered with a rubber septum was charged with alcohol compound 1 (1.0 mmol), toluene derivative 2 (4.0 mmol), and Bu4NI (36.9 mg, 10 mol%) in MeCN (2.0 mL). To this mixture was added TBHP (70% wt/v in H2O, 6.0 equiv) at r.t. The rubber septum was then replaced by a Teflon-coated screw cap, and the reaction vessel was placed in an oil bath at 80 C for 24 h. After the completion of the reaction (monitored by TLC), the mixture was cooled to r.t. The resulting solution was poured into a mixture of sat. aq Na2S2O3 (5 mL) and sat. aq NaHCO3 (5 mL), and extracted with EtOAc (2 ×). The combined organic layers were dried (anhyd Na2SO4) and the solvents were removed in vacuo. The residue was purified by flash chromatography on silica gel (eluent: PE/EtOAc) to give the desired product. Benzyl Benzoate (3a)12a Colorless oil; yield: 150 mg (71%). 1H NMR (500 MHz, CDCl3): δ = 8.18 (d, J = 7.5 Hz, 2 H), 7.61 (t, J = 7.5 Hz, 1 H), 7.54 (d, J = 8.0 Hz, 2 H), 7.48 (dd, J = 12.5, 7.5 Hz, 4 H), 7.41 (d, J = 7.0 Hz, 1 H), 5.45 (s, 2 H). 13C NMR (125 MHz, CDCl3): δ = 166.46, 136.19, 133.12, 130.24, 12.80, 128.70, 128.48, 128.34, 128.27, 66.76. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With lithium hexamethyldisilazane In neat (no solvent) at 0 - 20℃; for 3h; | 2.2. General procedure for transesterification reactions General procedure: Ester (1 mmol) and alcohol (3 mmol) were added in a round bottom flask, followed by the addition of base LiHMDS (2 mmol) at 0 °C. The reaction was stirred at room temperature for about 3 h. The reaction was monitored by TLC. After completion of the reaction, ethyl acetate was added to the reaction mixture and washed with water three times. The ethyl acetate layer was evaporated on the rota evaporator, and the crude products were purified by column chromatography in pet ether. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With lithium hexamethyldisilazane In neat (no solvent) at 0 - 20℃; for 3h; | 2.2. General procedure for transesterification reactions General procedure: Ester (1 mmol) and alcohol (3 mmol) were added in a round bottom flask, followed by the addition of base LiHMDS (2 mmol) at 0 °C. The reaction was stirred at room temperature for about 3 h. The reaction was monitored by TLC. After completion of the reaction, ethyl acetate was added to the reaction mixture and washed with water three times. The ethyl acetate layer was evaporated on the rota evaporator, and the crude products were purified by column chromatography in pet ether. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With lithium hexamethyldisilazane In neat (no solvent) at 0 - 20℃; for 3h; | 2.2. General procedure for transesterification reactions General procedure: Ester (1 mmol) and alcohol (3 mmol) were added in a round bottom flask, followed by the addition of base LiHMDS (2 mmol) at 0 °C. The reaction was stirred at room temperature for about 3 h. The reaction was monitored by TLC. After completion of the reaction, ethyl acetate was added to the reaction mixture and washed with water three times. The ethyl acetate layer was evaporated on the rota evaporator, and the crude products were purified by column chromatography in pet ether. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With lithium hexamethyldisilazane In neat (no solvent) at 0 - 20℃; for 3h; | 2.2. General procedure for transesterification reactions General procedure: Ester (1 mmol) and alcohol (3 mmol) were added in a round bottom flask, followed by the addition of base LiHMDS (2 mmol) at 0 °C. The reaction was stirred at room temperature for about 3 h. The reaction was monitored by TLC. After completion of the reaction, ethyl acetate was added to the reaction mixture and washed with water three times. The ethyl acetate layer was evaporated on the rota evaporator, and the crude products were purified by column chromatography in pet ether. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With lithium hexamethyldisilazane In neat (no solvent) at 0 - 20℃; for 3h; | 2.2. General procedure for transesterification reactions General procedure: Ester (1 mmol) and alcohol (3 mmol) were added in a round bottom flask, followed by the addition of base LiHMDS (2 mmol) at 0 °C. The reaction was stirred at room temperature for about 3 h. The reaction was monitored by TLC. After completion of the reaction, ethyl acetate was added to the reaction mixture and washed with water three times. The ethyl acetate layer was evaporated on the rota evaporator, and the crude products were purified by column chromatography in pet ether. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With lithium hexamethyldisilazane In neat (no solvent) at 0 - 20℃; for 3h; | 2.2. General procedure for transesterification reactions General procedure: Ester (1 mmol) and alcohol (3 mmol) were added in a round bottom flask, followed by the addition of base LiHMDS (2 mmol) at 0 °C. The reaction was stirred at room temperature for about 3 h. The reaction was monitored by TLC. After completion of the reaction, ethyl acetate was added to the reaction mixture and washed with water three times. The ethyl acetate layer was evaporated on the rota evaporator, and the crude products were purified by column chromatography in pet ether. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With lithium hexamethyldisilazane; In neat (no solvent); at 0 - 20℃; for 3h; | General procedure: Ester (1 mmol) and alcohol (3 mmol) were added in a round bottom flask, followed by the addition of base LiHMDS (2 mmol) at 0 C. The reaction was stirred at room temperature for about 3 h. The reaction was monitored by TLC. After completion of the reaction, ethyl acetate was added to the reaction mixture and washed with water three times. The ethyl acetate layer was evaporated on the rota evaporator, and the crude products were purified by column chromatography in pet ether. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With lithium hexamethyldisilazane In neat (no solvent) at 0 - 20℃; for 3h; | 2.2. General procedure for transesterification reactions General procedure: Ester (1 mmol) and alcohol (3 mmol) were added in a round bottom flask, followed by the addition of base LiHMDS (2 mmol) at 0 °C. The reaction was stirred at room temperature for about 3 h. The reaction was monitored by TLC. After completion of the reaction, ethyl acetate was added to the reaction mixture and washed with water three times. The ethyl acetate layer was evaporated on the rota evaporator, and the crude products were purified by column chromatography in pet ether. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With lithium hexamethyldisilazane In neat (no solvent) at 0 - 20℃; for 3h; | 2.2. General procedure for transesterification reactions General procedure: Ester (1 mmol) and alcohol (3 mmol) were added in a round bottom flask, followed by the addition of base LiHMDS (2 mmol) at 0 °C. The reaction was stirred at room temperature for about 3 h. The reaction was monitored by TLC. After completion of the reaction, ethyl acetate was added to the reaction mixture and washed with water three times. The ethyl acetate layer was evaporated on the rota evaporator, and the crude products were purified by column chromatography in pet ether. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With lithium hexamethyldisilazane In neat (no solvent) at 0 - 20℃; for 3h; | 2.2. General procedure for transesterification reactions General procedure: Ester (1 mmol) and alcohol (3 mmol) were added in a round bottom flask, followed by the addition of base LiHMDS (2 mmol) at 0 °C. The reaction was stirred at room temperature for about 3 h. The reaction was monitored by TLC. After completion of the reaction, ethyl acetate was added to the reaction mixture and washed with water three times. The ethyl acetate layer was evaporated on the rota evaporator, and the crude products were purified by column chromatography in pet ether. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With lithium hexamethyldisilazane In neat (no solvent) at 0 - 20℃; for 3h; | 2.2. General procedure for transesterification reactions General procedure: Ester (1 mmol) and alcohol (3 mmol) were added in a round bottom flask, followed by the addition of base LiHMDS (2 mmol) at 0 °C. The reaction was stirred at room temperature for about 3 h. The reaction was monitored by TLC. After completion of the reaction, ethyl acetate was added to the reaction mixture and washed with water three times. The ethyl acetate layer was evaporated on the rota evaporator, and the crude products were purified by column chromatography in pet ether. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With lithium hexamethyldisilazane In neat (no solvent) at 0 - 20℃; for 3h; | 2.2. General procedure for transesterification reactions General procedure: Ester (1 mmol) and alcohol (3 mmol) were added in a round bottom flask, followed by the addition of base LiHMDS (2 mmol) at 0 °C. The reaction was stirred at room temperature for about 3 h. The reaction was monitored by TLC. After completion of the reaction, ethyl acetate was added to the reaction mixture and washed with water three times. The ethyl acetate layer was evaporated on the rota evaporator, and the crude products were purified by column chromatography in pet ether. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 91% 2: 91% | In neat (no solvent) at 20℃; for 2h; | General procedure for aroylation of alcohols 2a-i bygrinding with N-aroylbenzotriazoles (1a-d): General procedure: A mixture of N-aroylbenzotriazole 1 (1.0 mmol) and the corresponding alcohol 2 (2.0 mmol) was ground together in a mortar using pestle for the time described in Tables 1 and 2. Completion of the reaction was monitored by TLC in hexane:dichloromethane(1:1) solvent systems. The resulting mixture was purified by preparative thin layer chromatography (silica gel, elution with 50% dichloromethane/hexane) to provide desired ester 3 and benzotriazole (4). |
Tags: 120-51-4 synthesis path| 120-51-4 SDS| 120-51-4 COA| 120-51-4 purity| 120-51-4 application| 120-51-4 NMR| 120-51-4 COA| 120-51-4 structure
[ 72985-23-0 ]
6-Methylisobenzofuran-1(3H)-one
Similarity: 0.98
[ 23405-32-5 ]
Methyl 1-oxo-1,3-dihydroisobenzofuran-5-carboxylate
Similarity: 0.98
[ 54120-64-8 ]
5-Methylisobenzofuran-1(3H)-one
Similarity: 0.98
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H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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