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CAS No. : | 495-40-9 | MDL No. : | MFCD00009397 |
Formula : | C10H12O | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | FFSAXUULYPJSKH-UHFFFAOYSA-N |
M.W : | 148.20 | Pubchem ID : | 10315 |
Synonyms : |
|
Num. heavy atoms : | 11 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.3 |
Num. rotatable bonds : | 3 |
Num. H-bond acceptors : | 1.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 46.25 |
TPSA : | 17.07 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -5.24 cm/s |
Log Po/w (iLOGP) : | 2.13 |
Log Po/w (XLOGP3) : | 2.77 |
Log Po/w (WLOGP) : | 2.67 |
Log Po/w (MLOGP) : | 2.4 |
Log Po/w (SILICOS-IT) : | 2.85 |
Consensus Log Po/w : | 2.56 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 2.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.71 |
Solubility : | 0.289 mg/ml ; 0.00195 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.78 |
Solubility : | 0.244 mg/ml ; 0.00164 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -3.52 |
Solubility : | 0.0446 mg/ml ; 0.000301 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.0 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P210-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H227-H315-H319 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With potassium permanganate; Rexyn 101 H ion exchange resin In dichloromethane for 5.45h; Heating; | |
92% | With manganese(IV) oxide; potassium permanganate In dichloromethane at 20℃; for 27h; | |
92% | With tert.-butylhydroperoxide In water monomer at 20℃; for 48h; Sealed tube; |
91% | With iron (ΙΙΙ) nitrate nonahydrate; 1-hydroxy-pyrrolidine-2,5-dione; oxygen In phenyl cyanide at 90℃; for 24h; | |
90% | With tert.-butylhydroperoxide In 2,2,4-trimethypentane; dichloromethane for 36h; Ambient temperature; | |
90% | With tert.-butylhydroperoxide; dirhodium(II) tetra-2-(methanesulfonylimino)pyrrolidine In methanol; water monomer at 20℃; for 20h; | |
90% | With pyridine; N-hydroxyphthalimide; tetra-n-butylammonium tetrafluoroborate; oxygen In 2,2,2-trifluoroethanol; acetonitrile at 25 - 30℃; Electrolysis; | 2.2.1 Procedure for mono-oxidation General procedure: An undivided cell was equipped with a magnet stirrer, platinum plate electrode (1.0×1.0×0.3 cm3), as the working electrode and counter electrode. Substrate (0.5 mmol),nBu4NBF4 (0.5 mmol, 164.6 mg), N-hydroxyphthalimide (NHPI, 0.1 mmol, 16.3 mg), and pyridine (1.0 mmol, 82 μL)were added to MeCN/2,2,2-trifluoroethan-1-ol (TFE) (5:1,3 mL). The electrolysis was conducted in an undivided cell equipped with O2 balloon at a constant current of 5 mA at room temperature (25-30 °C). When the reaction was completed, the solvent was removed under reduced pressure and the remaining crude product was purified by column chromatography over silica gel (petroleum ether/ethyl acetate(PE/EA)=30:1-10:1) to afford the corresponding aromatic ketone product. |
89% | With NaBrO3; tetrabutylammonium hydrogensulfate In water monomer; acetonitrile at 80℃; for 24h; | |
89% | With iron (ΙΙΙ) nitrate nonahydrate; N-hydroxyphthalimide; oxygen In acetonitrile at 100℃; for 15h; | 2 Example 2 A round bottom flask equipped with a magnetic stir bar and a reflux condenser was charged with 5.3 g of butylbenzene, 0.4 g of ferric nitrate nonahydrate, 0.3 g of NHPI, and 30 mL of acetonitrile. After adding, put on the three-way valve to connect the oxygen ball,Under the action of an air pump, the air in the reaction system was replaced with oxygen. The temperature of the oil bath was raised to 100. After 15 hours of reaction under stirring and refluxing, the conversion rate of butylbenzene was detected by gas chromatography. 91% stopped the reaction. After the solvent in the reaction system was distilled off under reduced pressure, it was separated by column chromatography (petroleum ether/ethyl acetate=100:1-30:1) to obtain 5.28 g (colorless liquid) of the product phenbutanone, with a yield of 89% . |
88% | With potassium permanganate; copper(II) sulphate for 72h; | |
88% | With NaBrO3; sulfuric acid; mesoporous silica at 20℃; for 4.5h; | |
88% | With 2-methylanthracene-9,10-dione; oxygen In acetonitrile for 7h; Irradiation; | 2. General Experimental Procedures 2.1. Stirring reaction procedures General procedure: Ethylbenzene (1, 1 mmol), 2-Methylanthraquinone (10 mol%) and CH3CN (3.0 mL) were added to a reaction vessel equipped with magnetic stirring bar, and the reaction vessel was irradiated with 6 W blue LED (405 nm) for 7 h under O2 atmosphere. After the reaction was completed, the mixture was analyzed by GC and the yield was determined using 1,4-Dioxane as the internal standard. The reaction solution was concentrated under reduced pressure to yield crude product, which was purified by column chromatography (silica gel) to give the desired product for characterization. |
86% | With potassium peroxomonosulfate; potassium bromide In nitromethane at 20℃; for 24h; | |
85% | With tert.-butylhydroperoxide; Sodium hydrogenocarbonate; bis-[(trifluoroacetoxy)iodo]benzene In dichloromethane at -30 - 20℃; for 6h; | |
85% | With N-hydroxyphthalimide; 6-((cobalt(II) 4,9,16,23-tetraaminephthalocyanin-4-yl))cellulose; oxygen; potassium hydroxide In o-dimethylbenzene for 12h; Reflux; Green chemistry; | Typical procedure for the oxidation of tetraline General procedure: N-Hydroxyphthalimide (0.01 g, 0.06 mmol) was added to a two-necked flask equipped with a gas bubbling tube containing colloidal of CoPcCell (0.05 g), tetraline (0.13 g, 1.00 mmol) and KOH (0.25 mmol) in o-xylene (5 mL). The mixture was stirred under reflux conditions in O2 atmosphere provided with a balloon. The reaction temperature was raised to refluxing o-xylene. The progress of the reaction was followed by TLC. Upon completion, CoPcCell was separated by filtration and washed with acetone (5 mL). Tetralone was isolated from the mixture using column chromatography with n-hexane:ethyl acetate (10:1) in 88% yield. |
82% | With sodium chlorine monoxide; 1-glycyl-3-methylimidazolium chloride-copper(II) complex at 20℃; for 11h; Neat (no solvent); | |
81% | With iodobenzene; 3-chloro-benzenecarboperoxoic acid; potassium bromide In water monomer at 60℃; for 18h; | |
80% | With potassium permanganate at 20℃; for 6h; | |
80% | With tert.-butylhydroperoxide; C45H52CuN4O3 In decane; acetonitrile at 70℃; for 18h; | |
80% | With tert.-butylhydroperoxide; V2O5/TiO2 In water monomer at 80℃; for 8h; Sealed tube; Green chemistry; | |
78% | With NaBrO3; 1-butyl-3-methyl-1H-imidazol-3-ium bromide at 70℃; for 13h; | |
72% | With 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione In fluorobenzene; dimethyl sulfoxide at 80℃; for 8h; | |
72% | With 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione In dimethyl sulfoxide at 80℃; for 8h; | |
67% | With air; Sodium hydrogenocarbonate; 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; | |
63% | With potassium permanganate; Montmorillonite K10 at 23℃; for 0.416667h; microwave irradiation; | |
58% | With potassium permanganate In acetonitrile at 20℃; for 32h; | |
47% | With [bis(acetoxy)iodo]benzene; tert-butyl hydroxyperoxide; 3-chloro-benzenecarboperoxoic acid In 2,2,2-trifluoroethanol at 20℃; for 12h; | |
42% | With lithium perchlorate In water monomer; acetonitrile at 20℃; for 5h; Electrolysis; | |
40% | With manganese(II) chloride tetrahydrate; water monomer; 3-chloro-benzenecarboperoxoic acid; 4,4',4-tri-tert-butyl-2,2':6',2-terpyridine In acetonitrile at 0 - 20℃; chemoselective reaction; | |
31.2% | With tert.-butylhydroperoxide In acetonitrile at 69.84℃; for 5h; | |
16% | With tert.-butylhydroperoxide; copper chloride (I) In decane; <i>tert</i>-butyl alcohol at 50℃; for 12h; | Cu-Catalyzed Aerobic C-H Oxygenation of 1a; Typical Procedure: General procedure: To a test tube charged with CuCl (2.0 mg, 0.02 mmol) andisochroman (1a; 251 μL, 2.0 mmol) in t-BuOH (20 mL) wasadded TBHP (5.0-6.0 M in decane, 10.9 μL, 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. |
13% | With PEG-1000; carbon dioxide; oxygen; cobalt(II) diacetate at 100℃; for 12h; Autoclave; Neat (no solvent); | |
With manganese oleate; oxygen | ||
67 % Turnov. | With N-hydroxyphthalimide; oxygen; cobalt(II) 2,4-pentanedionate In glacial acetic acid at 100℃; for 6h; | |
With cerium(IV) dioxide; NaBrO3 In 1,4-dioxane; water monomer; glacial acetic acid at 95℃; for 24h; | ||
88 % Chromat. | With dihydrogen peroxide In acetonitrile at 80℃; for 5h; | |
With oxygen at 135℃; for 5h; | ||
With oxygen In water monomer; acetonitrile at 5 - 10℃; Irradiation; chemoselective reaction; | ||
79.5 mg | With chromium(VI) oxide; tert.-butylhydroperoxide In 1,2-dichloro-ethane at 70 - 75℃; | |
With oxygen at 140 - 150℃; for 5 - 10h; | 13; 14 Examples 11-18 These examples further illustrate the process of this invention for the oxidation of diphenyl methane to benzophenone, n-propyl benzene to propiophenone, n-butyl benzene to n-butyrophenone 4-ethyl toluene to 4-methyl acetophenone and benzhydrol to benzophenone at different reaction conditions. [0122] The oxidation reactions were carried out using the catalyst prepared in Example-10 and by the method similar to that described in Example-1 except that the reaction conditions are different. The results obtained at different reaction conditions are given in Tables 3 and 4. | |
With oxygen In 1,3-dimethylbenzene for 20h; Heating / reflux; | 21 Examples 19-22 These examples further illustrate the process of this invention for the oxidation of ethyl benzene to acetophenone, n-propyl benzene to propiophenone, n-butyl benzene to n-butyrophenone and diphenyl methane to benzophenone with continuous removal of the reaction water during the oxidation reaction, using the catalyst prepared in Example-1. [0125] The catalytic oxidation reactions were carried out, by the method similar to that described in Example-1 except that a Dean-Stark trap was used between the reactor and the reflux condenser, each of the reactions is carried out with or without using a non-aqueous solvent, each of the reactions was carried out under reflux and the water formed in each of the reactions was removed continuously during the reaction. The results obtained are given in Table 5. | |
78 %Chromat. | With potassium peroxomonosulfate; water monomer; potassium bromide In acetonitrile at 45℃; | General procedure General procedure: To a solution of aromatic compound 1a-q (1 mmol) in CH3CN (6 mL) and H2O (0.5 mL) were added KBr (0.5 mmol) and Oxone (2.2 mmol), and the mixture was stirred at 45°C. After completion (monitored by TLC), the reaction mixture was filtered and the solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate, washed with saturated aqueous Na2S2O3 and brine, dried over anhydrous Na2SO4. Removal of the solvent under vacuum afforded the crude product, which was purified by column chromatography using hexane/ethyl acetate as eluent (20 - 80 : 1). |
98 %Chromat. | With copper(II) tetrasulfophthalocyanine supported on three-dimensional nitrogendopedgraphene-based frameworks; air In water monomer at 20℃; for 12h; | |
With dihydrogen peroxide; oxygen In water monomer; acetonitrile at 70℃; for 7h; Green chemistry; | General procedure for oxidation of alkyl aromatics General procedure: Alkyl aromatics (5 mmol) in 10 mL acetonitrile and the polymer supported cobalt catalyst (60 mg) were in turn introduced into a50 mL round bottomed flask equipped with a condenser and a thermometer in an oil bath. The reaction was carried under oxygen atmosphere (1 atm) with 1 mmol H2O2. Then, the catalyst wasremoved by filtration, and the solvent was evaporated in vacuum. The product was filtered, washed thoroughly with water and extracted with ether, then dried with anhydrous Na2SO4 and analyzed by GC and GC-MS. | |
89 %Chromat. | With MnO2 nanostructure coated on cellulose; air In o-dimethylbenzene at 120℃; for 10h; Green chemistry; | |
96 %Chromat. | With gold nanoparticles supported on three dimensional nitrogen-doped graphene; air In water monomer at 20℃; for 5h; Green chemistry; regioselective reaction; | |
95 %Chromat. | With oxygen In o-dimethylbenzene for 12h; Reflux; | |
With tert.-butylhydroperoxide In acetonitrile at 80℃; for 24h; Green chemistry; | Oxidation of alkyl aromatics General procedure: In a typical procedure, to a mixture of catalyst (0.5 mmol), acetonitrile (10 mL) and alkyl aromatics (5 mmol) were added tert-butyl hydroperoxide (15 mmol) in turn. Samples were withdrawn periodically. After required hours, the reaction mixture was cooled to room temperature. | |
70 %Chromat. | With potassium hydroxide In para-xylene at 100℃; for 6h; Green chemistry; | |
85 %Chromat. | With potassium carbonate In para-xylene at 100℃; for 8h; Green chemistry; | |
75 %Chromat. | With N-hydroxyphthalimide In para-xylene at 100℃; for 8h; Green chemistry; | |
With cobalt(II) tetrasulfophthalocyanine supported on wool; air In water monomer for 13h; Reflux; | ||
77 %Chromat. | With N-hydroxyphthalimide; oxygen; Co(OAc)2.4H2O In pyridine; acetic acid butyl ester at 90℃; for 12h; | |
With Manganese dioxide nanostructures coated on natural silk In o-dimethylbenzene for 10h; Reflux; | 3.2. Oxidation of alkyl arenes; General procedure General procedure: In a typical reaction, an alkyl arene (1.0 mmol), MnO2silk(0.09 g, 10 mol% of MnO2), and o-xylene (5.0 mL) were added to atwo-necked flask. The mixture was stirred under reflux conditionsand air blowing. The thin layer chromatography (TLC) method was used to investigate the progress of the reaction. Upon completion,analysis of the crude product has been done by GC method. | |
92 %Chromat. | With potassium permanganate; 1,1,3,3-tetramethylguanidine sulfonic acid hydrochloride In hexane at 20℃; for 10h; Green chemistry; | 3.1.2. Oxidation of alkyl arenes, alcohols, and sulfides; a general procedure General procedure: An alkyl arene, alcohol, or sulfide (1.00mmol) was added to a round-bottomed flask containing potassium permanganate (6.33mmol, 1.00 g) and GSA (0.02 g, 8.6 mol%) in n-hexane (10 mL) with a magnetic stirrer. The reaction mixture was stirred at room temperature for indicated times as given in Tables 2, 4 and 5, respectively, while the progress of the reaction was followed by thin layer chromatography (TLC). Upon completion, the reaction mixture was filtered and the filtrate was analyzed by the GC method. |
67 %Chromat. | With dihydrogen peroxide In acetonitrile at 20℃; for 18h; Green chemistry; | 4.4 General Catalytic Procedure for Oxidation of Alcohols, Alkenes and Alkyl Arenes General procedure: Alcohols, alkenes or alkyl arenes (1.00mmol) was added toa round-bottomed flask containing H2O2(1.50-2.00mmol,30%) and MIL-101(Cr)-guanidine-Fe (0.025g) in acetonitrile (10ml) with a magnetic stirrer. The reaction mixture was stirred at room temperature for indicated times as given in Tables 3, 5 and 7, respectively, while the progress of the reaction was followed by thin layer chromatography (TLC).Upon compilation the reaction, the reaction mixture was filtered and the filtrate analyzed by GC method. The conversions were determined from the integrals of the GC analysis. |
With dihydrogen peroxide; potassium hydroxide In ethanol; water monomer at 90℃; for 24h; Green chemistry; | Typical procedure for the oxidation of ethylbenzene Ethylbenzene (0.10 g, 1.00 mmol) was added to a round-bottomed flask containing of H2O:EtOH (1:1) (5 mL), PdNPs/TiO2 nanotubes/Ti plate, and KOH (0.03 g, 0.5 mmol). The mixture was heated to 90 °C, and H2O2(3 mmol) was added dropwise to the reaction vessel during 0.5 h. After 24 h,the plate was removed, the solvent was evaporated under vacuum, and the product was analyzed by GC. The convesions were calculated in the presence of internal standard using integrals of the GC analyses. | |
72 %Chromat. | With tert.-butylhydroperoxide; C29H25Cl2N4Ru(1+)*F6P(1-) In acetonitrile at 60℃; for 5h; Schlenk technique; Inert atmosphere; | |
98 %Chromat. | With oxygen; sodium trifluoro-methanesulfinate In acetonitrile at 25℃; for 12h; Irradiation; Green chemistry; | |
With oxygen In neat (no solvent) at -10.16℃; for 10h; Green chemistry; | ||
With N-hydroxyphthalimide; oxygen In acetonitrile at 75℃; for 24h; | 2.3 General Procedure for Substrate Oxidation General procedure: The general procedure for the oxidation of alkanes and alcoholswas presented as follows: The substrate (10 mmol) wasadded to a 15 mL solution containing CoPc(CONH2)4 andNHPI. The mixture was stirred with a magnetic stirrer in athree-necked round-bottomed flask fitted with a thermometer,a reflux condenser, and an oxygen gas inlet tub, andthen was placed in a temperature-controlled oil bath, andat the same time, oxygen is controlled to enter the systemat a certain flow rate. After the reaction was completed, thereaction solution was centrifuged to separate the catalyst,and benzonitrile was added to the reaction solution as theinternal standard for GC analysis. The solvent was removedunder reduced pressure and the crude product was purifiedby silica-gel column chromatography using a mixture ofpetroleum ether and ethyl acetate (20:1 vol/vol) as solventsystem. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With dinitrogen monoxide In 1,2-dichloro-ethane at 150℃; for 7.5h; | |
100% | With dinitrogen monoxide In 1,2-dichloro-ethane at 150℃; for 7.5h; | |
100% | With silica-supported Jones reagent In dichloromethane for 0.00269444h; |
100% | With oxygen In 1,3,5-trimethyl-benzene at 60℃; for 5h; | 8.13 Example 8 Application of this method in the reaction of other alcohols to aldehydes and ketones The typical reaction steps are as follows:1 mmol of the starting alcohol of the reactant column shown in Table 2,OH - Ni3In-LDH 14 mg,Mesitylene 5mL were added to the reactor,Into the oxygen,Atmospheric reaction,The reaction was stirred at 60 for a certain period of time.The solid catalyst was removed by filtration,Using gas chromatography internal standard method (chlorobenzene as internal standard) to analyze the content of liquid products,Calculate yield. |
99% | With potassium hexafluorophosphate; tert.-butylnitrite; 9-azabicyclo<3.3.1>nonane-N-oxyl; oxygen In water at 60℃; for 5h; Autoclave; Green chemistry; | |
99% | With oxygen; C26H21BrO In dichloromethane for 12h; Irradiation; | |
98% | With dimethyl sulfoxide; triphenylphosphine dibromide 1:1 addition complex; triethylamine In dichloromethane at -78 - 20℃; for 3.25h; | |
95% | With sodium tetrahydroborate; oxygen; potassium carbonate In water; isopropyl alcohol at 20℃; for 0.333333h; | |
95% | With C32H25Cl2N6O2Rh2(1+)*Cl(1-); sodium hydroxide In water at 100℃; for 16h; Sealed tube; Green chemistry; | |
95% | With basolite C300; 9-azabicyclo<3.3.1>nonane-N-oxyl; oxygen In 1,2-dichloro-ethane at 70℃; for 15h; Green chemistry; | 5. General procedures of the aerobic oxidation catalyzed by HKUST-1/ABNO General procedure: A 15 mm flame-dried test tube, which was equipped with a magnetic stir bar and charged with alcohol (0.5 mmol, in case of solid), HKUST-1 (10 mol %, 0.05 mmol), ABNO (5 mol %, 0.025 mmol), and Cs2CO3 (1.0 equiv, 0.5 mmol), was evacuated and backfilled with oxygen (this process was repeated 3 times). After 0.5 mL of DCE was added, alcohol (0.5 mmol, in case of liquid), and DCE (0.5 mL) were added in sequence. The reaction mixture was stirred for 15 h at room temperature under O2 balloon. The reaction was diluted by adding CH2Cl2 and filtered through celite. The solvent was removed under vacuo. The residue was purified by column chromatography to give the desired product |
93% | With sodium tetrahydroborate; 1% Pd/C; water; oxygen; potassium carbonate In ethanol at 20℃; for 0.33h; | |
93% | With 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione In neat (no solvent) at 20℃; for 1h; Milling; | |
92% | With 2,6-dimethylpyridine; 9-azabicyclo<3.3.1>nonane-N-oxyl; sodium perchlorate In acetonitrile for 8.66h; Inert atmosphere; Electrochemical reaction; | 3.4. Preparation Electrolysis Experiments General procedure: The preparative electrolysis experiments were conducted with in an undivided cell containing0.1 M NaClO4-CH3CN solution (15 mL), alcohol substrate (1.0 mmol), ABNO (0.1 mmol),and 2,6-lutidine (1.0 mmol) at a constant current of 10.0 mA with moderate magnetic stirring for8.5 h in the atmosphere. Two square platinum sheets were employed as the anode and cathode,respectively. The electrolytic reaction was monitored by gas chromatography (GC) on a GC-2010system (Shimadzu, Kyoto, Japan) equipped with a SH-Rtx-Was polar column and a flame ionizationdetector (FID). Both the injector and detector were maintained at 220 °C, the carrier gas is nitrogen,and the flow rate is 1.2 mL/min. The initial oven temperature of 100 °C was held for 2 min andthen ramped up at 15 °C per min to 220 °C. This final temperature was held for 8 min. After thereaction was finished, the resulting mixture was concentrated in a rotary evaporator (Heidolph,Schwabach, Germany) and purified by column chromatography on silica gel using petroleum andethyl acetate 15:1) as eluent to afford the products. The products were confirmed by GC-MS, 1H-NMR,and 13C-NMR. NMR spectroscopy was carried out on a Bruker Avance III spectrometer (Bruker,Fällanden, Switzerland). The GC-MS analysis was measured on Thermo Trace ISQ instrument (ThermoFisher Nicolet,Waltham, MA, USA) with TG 5MS capillary column.Acetophenone (colorless oil, yield 80%): |
92% | With diisopropyl-carbodiimide In toluene at 120℃; for 24h; Inert atmosphere; Sealed tube; | |
89% | With Iron(III) nitrate nonahydrate; oxygen; 2,3-dicyano-5,6-dichloro-p-benzoquinone In 1,2-dichloro-ethane at 60℃; for 3h; Schlenk technique; Green chemistry; | |
88% | With oxygen In acetonitrile at 20℃; for 1.5h; UV-irradiation; | |
85% | With magnesium sulphate; vanadyl(IV) sulphate pentahydrate; 4-nitrophenyl(phenyl)methanol; 4,4'-di-tert-butyl-2,2'-bipyridine In water at 0 - 90℃; for 120h; | 4.6 Oxidation of alcohols under open-air atmosphere General procedure: VOSO4·5H2O (126.5 mg, 0.5 mmol), 4,4′-di-tert-butyl-2,2′-bipyridyl (268.4 mg, 1 mmol), and p-nitrobenzhydrol (229.3 mg, 0.05 mmol) were placed in a 100 mL round-bottomed flask, and then water (50 mL) was added. Next, the mixture was stirred, and then anhydrous MgSO4 (18.06 g, 150 mmol) was slowly added into the mixture (cooling by ice water). After that, substrate (10 mmol) was added into the mixture at room temperature, and the mixture was stirred at 90 °C for the appropriate time under open-air atmosphere. After the reaction, the mixture was extracted with ethyl acetate and dried over anhydrous MgSO4. The extracts were concentrated in vacuo. Purification of the products was carried out by silica gel column chromatography using hexane and diethyl ether as eluent to afford the analytically pure ketones. In Table 7 (entries 3, 7, and 8), crude products were purified by recrystallization with ethyl acetate in refrigerator, afforded analytically pure ketones. The product was identified by comparison with the commercially available sample using 1H NMR spectroscopy. |
82% | With iodine; oxygen In acetonitrile at 20℃; for 4h; Irradiation; | |
82% | With C27H42ClN2PRu; caesium carbonate In 5,5-dimethyl-1,3-cyclohexadiene at 140℃; for 48h; Inert atmosphere; Glovebox; Sealed tube; | |
78% | In water at 0℃; Electrochemical reaction; | |
72% | With 5,6-difluoro-2-(1-phenylethyl)benzo[d][1,2]selenazol-3(2H)-one; bromine In dichloromethane at -35℃; for 24h; | |
68% | With palladium 10% on activated carbon; chlorobenzene; potassium hydroxide In methanol; water at 60℃; for 6h; Inert atmosphere; | Procedure General procedure: The starting alcohol (1 mmol), KOH (3.0mmol) and catalyst (10 mol% Pd) were added to a Schlenkflask. In another Schlenk flask, the oxygen in the solvent(MeOH : H2O = 5:1, v/v, 6.0 mL) was removed by the freezepump-thaw and purging method. The aqueous solvent was transferred to the reaction flask of the starting alcohol by cannulation. Afterwards, chlorobenzene (3.0 mmol) was added using a syringe, and the reaction was kept under argon. Upon completion of the reaction based on TLC monitoring, the Pd/C was filtered off on celite and the solvent was removed by rotary evaporation. A brine solution was added to the residue and the product was extracted using methylene chloride. The organic layer was collected, dried with anhydrous magnesium sulfate, and concentrated byrotary evaporation. The mixture was purified via column chromatography using various hexane/EtOAc eluent systems. All products were known and characterized by comparing their 1H NMR spectra with those that have been published in the literature. |
61% | With 1,10-Phenanthroline; iron(III)-acetylacetonate; potassium carbonate In toluene for 48h; Reflux; Green chemistry; | |
39% | With tert.-butylhydroperoxide; oxygen In dichloromethane at 20℃; for 48h; | |
With chloroform; dinitrogen tetraoxide | ||
2 % Chromat. | With Geotrichum candidum IFO 4597 cells In water at 30℃; for 24h; | |
92 % Spectr. | With 3,3-dimethyldioxirane In acetone at 25℃; | |
With manganese(IV) oxide In dichloromethane | ||
86 % Chromat. | With phosphotungstate catalyst; dihydrogen peroxide; 1-butyl-3-methylimidazolium Tetrafluoroborate for 2h; Heating; | |
With copper at 280 - 300℃; | ||
With lyophilized cells of Rhodococcus ruber DSM 44541; acetone In phosphate buffer at 24℃; for 24h; | ||
With trimethylaluminum In toluene at 20℃; for 1h; | ||
With ketoreductase; acetone In phosphate buffer; pentane at 24.99℃; | ||
With sodium dichromate; sulfuric acid In dimethyl sulfoxide | ||
94 %Chromat. | With tert.-butylnitrite In toluene at 120℃; for 16h; Inert atmosphere; | Typical procedure for the oxidation of secondary benzylic alcohols (Table 2). General procedure: To a mixture of alcohol 1 (1 mmol), tridecane (50 μL, 0.205 mmol, internal standard) and toluene (0.5 mL) in a screw cap tube was added t-BuONO (198 μL, 1.5 mmol, 1.5 equiv.) under N2 atmosphere. The solution was stirred at 120 °C for the indicated time in table 2. The reaction mixture was analyzed by GC and the product was isolated by column chromatography (SiO2) for the characterization. |
99 %Spectr. | With oxygen In methanol at 60℃; for 0.333333h; Flow reactor; | |
With 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione In ethyl acetate Reflux; | ||
With oxygen In toluene at 80℃; for 12h; Autoclave; Heating; | Reaction procedure for benzyl alcohol oxidation General procedure: Liquid-phase catalytic oxidation of benzyl alcohol was carriedout in a 25 mL two-neck-flask with reflux condenser and magnet-ically stirred autoclave heated in an oil bath under atmosphericpressure. Dioxygen was bubbled (10 mL/min) through a solution oftoluene (8 mL), benzyl alcohol (216 mg, 2 mmol), and catalyst (1.0 g)at 80C. The product samples were drawn at regular time intervalsand analyzed with a gas chromatography (Shimadzu GC-2010AF)having SE-30 capillary column and FID detector. The products werefurther confirmed using GC-MS (Shimadzu GCMS-2010) with a DB-5MS capillary column. After the reaction, the resulting mixture wascooled with ice bath and the catalyst was separated by centrifuga-tion and washed with solvent. After drying at room temperature invacuum, the recycled catalyst can be reused in the next run underthe same conditions. The conversion, yield of benzaldehyde andselectivity presented here are based on the GC calculations usingchlorobenzene as the internal standard reference compound. | |
77 %Chromat. | With sulfuric acid; Mn<SUP>II</SUP>((1R,2R)-N,N'-dimethyl-N,N'-bis-(phenyl-2-pyridinylmethyl)cyclohexane-1,2-diamine)(OTf)<SUB>2</SUB>; dihydrogen peroxide In water; acetonitrile at 25℃; for 1h; Inert atmosphere; Schlenk technique; | |
With oxygen In toluene at 80℃; for 4h; | ||
With NAD; alcohol dehydrogenase from Candida parapsilosis-W286A mutant; Bacillus megaterium ω-transaminase In aq. acetate buffer at 30℃; for 21h; Green chemistry; Enzymatic reaction; | ||
83 %Chromat. | With potassium carbonate In n-heptane at 80℃; for 24h; | S4. Procedure for the synthesis of aldehydes and ketones General procedure: A magnetic stir bar, 0.5 mmol alcohol and 3 mL n-heptane solvent were added to 20 mL glass tube. Then, 35mg catalyst and 10 mol% of K2CO3 were added. The glass tube containing reaction mixture was f itted withseptum and connected to a balloon containing one bar of air. Then the glass tube was placed into a preheatedaluminum block at 85°C. Temperature inside the reaction tube was measured to be 80 oC and this temperaturehas been taken as the reaction temperature. The reaction was allowed to progress under continuous stirringfor the required time at 80 °C. Af ter completion of the reaction, the glass tube was cooled down to roomtemperature. Afterwards, the catalyst was f iltered-off and washed with ethyl acetate. The solvent f rom thef iltrate containing the reaction products was removed in vacuum and the corresponding aldehyde/ketone waspurif ied by column chromatography. All products were analyzed by GC-MS and NMR spectroscopy analysis.In the case of yields determined the by GC, 100 μL n-hexadecane was added to the reaction vial containingthe products and diluted with ethyl acetate. Then, the reaction mixture containing catalyst and products wasf iltered through a plug of silica and the filtrate containing product was analyzed by GC. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With iodine at 100℃; | N-(5-ethyl-4-phenyl-1,3-thiazol-2-yl)-2-[4-(ethylsulfonyl)phenyl]acetamide(7b) ) Iodine(3.330 g, 13.1mmol) was added to 1-phenyl-1-butanone (1.947 g, 13.1 mmol) and thiourea (2.000 g, 26.3 mmol). The reactionmixture was stirred and heatedto 100 °C overnight. After cooling to room temperature, the reaction mixture was triturated with diethylether (about 50 mL) to remove any unreacted iodine and 1-phenyl-1-butanone. Thesolid residue was put in cold distilled water (100 mL) and treated with ammoniasolution to pH 9-10. The precipitation was collectedto afford 5-ethyl-4-phenyl-1,3-thiazol-2-amine (2.650 g, 13.0 mmol, 99% yield) as a yellowsolid. It was directly used in the next step without further purification. MS(ES+) m/z 205.1 (MH+). A solution of 5-ethyl-4-phenyl-1,3-thiazol-2-amine (89 mg, 0.4 mmol),[4-(ethylsulfonyl)phenyl]acetic acid (100 mg, 0.4 mmol), EDC (101 mg, 0.5 mmol)and HOBt (81 mg, 0.5 mmol) in dichloromethane (DCM) (5 mL) was stirred at RT overnight. Solvent was removed under reduced pressure and the residuewas purified by MDAP to afford N-(5-ethyl-4-phenyl-1,3-thiazol-2-yl)-2-[4-(ethylsulfonyl)phenyl]acetamide(7b) (76 mg, 40% yield) as a white solid. |
With iodine | ||
With iodine at 100℃; for 14h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With amalgamated zinc; hydrogen iodide In methanol for 5h; Irradiation; | |
97% | With hydrogen In diethylene glycol dimethyl ether for 30h; | |
97.3% | With hydrogen In 1,4-dioxane at 220℃; |
90% | Stage #1: propiophenone With iron(III) chloride In methanol at 20℃; for 0.05h; Stage #2: In methanol at 20℃; for 0.166667h; chemoselective reaction; | |
With methanol; copper chromite at 240℃; Hydrogenolyse; | ||
With copper-aluminium oxide at 150 - 180℃; Hydrogenolyse; | ||
With hydrogenchloride; amalgamated zinc | ||
With sodium ethanolate; hydrazine hydrate at 180℃; | ||
With hydrogen; nickel at 300℃; | ||
With formic acid; nickel at 300℃; | ||
With hydrogenchloride; amalgamated zinc | ||
With sulfuric acid; hydrogen; acetic acid at 50 - 60℃; | ||
With hydrazine | ||
With hydrogen In 1,3,5-trimethyl-benzene at 175℃; for 16h; | ||
> 98 %Chromat. | Stage #1: propiophenone In water for 0.25h; Green chemistry; Stage #2: With formic acid In water at 30℃; for 0.25h; Green chemistry; | Catalytic reaction General procedure: The hydrodeoxygenation (HDO) of vanillin using formic acid as hydrogen source was conducted in a 25-mL two-necked glass flask. Typically, 100-mg catalyst, 0.585-mmol substrate, and 5-mL water were added into the reactor, with one neck sealed by a rubber stopper and another connected with a reflux condenser. After stirring for 15min, 2.34-mL HCOOH (5 M) was injected and started the reaction time. The reaction temperature in this system was controlled by thermocouple. The reaction solution was taken at certain intervals, extracted with ethyl acetate and analyzed the products by GC-FID with a Rtx-1071 column and GC-MS. m-cresol was used as an internal standard for quantitative analysis. The HDO process of other substrates were the same as the process mentioned earlier, only the reaction conditions were slightly different. To test the stability of Pd/HPC-NH2 catalyst, the recovered catalyst was reused after filtering, washing, and drying overnight. A small amount of lost catalyst was replenished with the first used catalyst. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With Aluminum(III) chloride hexahydrate; urea-hydrogen peroxide; 1-butyl-3-methylimidazolium Tetrafluoroborate at 60℃; for 4h; | |
84% | With [bis(acetoxy)iodo]benzene; iron(III) chloride hexahydrate In acetic acid at 50℃; for 24h; Inert atmosphere; | |
83% | Stage #1: propiophenone With [hydroxy(tosyloxy)iodo]benzene for 0.025h; microwave irradiation; Stage #2: With magnesium chloride for 0.0333333h; microwave irradiation; Further stages.; |
74% | With N-chloro-succinimide; toluene-4-sulfonic acid In acetonitrile for 4h; Reflux; | 2-Chloro-1-(p-tolyl)propan-1-one S1 General procedure: Unrecrystallised N-chlorosuccinimide (NCS) (8.95 g, 67 mmol) was added to a stirring solution of 4'-methylpropiophenone (9.93 g, 10 mL, 67 mmol) and p-toluenesulfonic acid monohydrate (19.12 g, 100.5 mmol, 1.5 eq) in acetonitrile (150 mL). The mixture was stirred under reflux conditions for 4 hours. Upon cooling, the solvent was evaporated under reduced pressure and the resulting residue was dissolved in dichloromethane (50 mL) and washed with water (2 x 20 mL). The organic layer was dried over magnesium sulfate and concentrated in vacuo to give the chloride S1 (8.69 g, 71%) as an orange oil which crystallised to a cream solid |
61% | With p-toluenesulfonyl chloride; lithium diisopropyl amide In tetrahydrofuran -78 deg C to room t., 1 h; | |
With sulfuryl dichloride | ||
With sulfuryl dichloride In tetrachloromethane | ||
With chloro-trimethyl-silane; tetrabutylammomium bromide In tetrahydrofuran; dimethyl sulfoxide; acetonitrile at 0 - 20℃; for 19h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With hydroxylamine hydrochloride; sodium acetate In ethanol; water at 95℃; | |
89% | With hydroxylamine hydrochloride; sodium acetate In ethanol; water for 2h; Reflux; | |
With ethanol; hydroxylamine |
With hydroxylamine hydrochloride; sodium acetate In ethanol; water Heating; | ||
With hydroxylamine hydrochloride In pyridine; ethanol Heating; | ||
With hydroxylamine hydrochloride; sodium acetate In ethanol; water Reflux; | ||
With hydroxylamine hydrochloride; sodium acetate In ethanol at 60℃; for 6h; | 87 First step, hydroxyamine hydrochloride (4.66 g) and NaOAc (11.07 g) were added to a solution of 1-(phenyl)-butanone (5 g) in EtOH (80 ml). The reaction mixture was stirred at 60°C for 6 h. EtOH was removed under reduced pressure. H2O (40 ml) was added to the residue, and the resulting solution was extracted with EtOAc (3 × 40 ml). The EtOAc of the combined organic layer was removed by rotary evaporation under reduced pressure to yield 1-(phenyl)-butanone oxime (5.5 g) as a pale yellowish solid. Second step, 1-(phenyl)-butanone oxime (5.5 g) and concentrated HCl (17.8 ml) in EtOH (50 ml) was subjected to hydrogenation at atmospheric pressure in the presence of 10% Pd/C (714 mg). The reaction solution was filtered and the filtrate was concentrated. The residue was suspended in EtOAc, and the suspension was filtered to yield 1-(phenyl)-butylamine hydrochloride (6.0 g) as a white solid. Third step, a mixture of 1-(phenyl)-butylamine (390 mg, the hydrochloride), 6-chloropurine riboside (200 mg) and triethylamine (3 ml) in PrOH (60ml) was heated to 70°C and reacted for 8 h. After evaporation of the reaction mixture, the residue was separated by column chromatography over silica gel and eluted with CHCl3-CH3OH (20: 1) to yield N6-[(+/-)-1-(phenyl)-butyl]-adenosine(225 mg) as a white solid: positive ESIMS mlz 400 [M + H]+ and 422 [M+Na]+; negative ESIMS mlz 398 [M - H]- and 434 [M + Cl]-; 1H NMR (300 MHz, DMSO-d6): the adenosine moiety δ 8.36 (1H, s, H-2), 8.31 (1H, brs, -NH), 8.14 (1H, s, H-8), 5.85 (1H, d, J= 6.0 Hz, H-1'), 5.40 (1H, m, -OH), 5.36 (1H, m, -OH), 5.15 (1H, J= 4.2 Hz, -OH), 4.58 (1H, m, H-2'), 4.12 (1H, m, H-3'), 3.94 (1H, m, H-4'), 3.66 (1H, m, H-5'a), 3.56 (1H, m, H-5'b); the (+/-)-1-(phenyl)-butyl moiety δ 7.44 (2H, d, J= 8.4 Hz, H-2", H-6"), 7.27 (2H, t, J= 8.4 Hz, H-3", H-5"), 7.16 (1H, t, J= 8.4 Hz, H-4"), 5.40 (1H, m, H-7"), 1.96 (1H, m, H-8"a), 1.75 (1H, m, H-8"b), 1.33 (2H, m, H-9"), 0.88 (3H, t, J= 7.2 Hz, H-10"); 13C NMR (75 MHz, DMSO-d6): the adenosine moiety δ 154.3 (s, C-6), 152.4 (d, C-2), 148.5 (s, C-4), 139.9 (d, C-8), 119.8 (s, C-5), 88.1 (d, C-1'), 86.0 (d, C-4'), 73.6 (d, C-3'), 70.8 (d, C-2'), 61.8 (t, C-5'); the (+/-)-1-(phenyl)-butyl moiety δ 144.5 (s, C-1"), 128.2 (d, C-2", C-6"), 126.7 (d, C-3", C-4", C-5"), 53.1 (d, C-7"), 38.1 (t, C-8"), 19.6 (t, C-9"), 13.7 (q, C-10"). | |
5.5 g | With hydroxylamine hydrochloride; sodium acetate In ethanol at 60℃; for 6h; | 87 First step, hydroxyamine hydrochloride (4.66 g) and NaOAc (11.07 g) were added to a solution of 1-(phenyl)-butanone (5 g) in EtOH (80 ml). The reaction mixture was stirred at 60° C. for 6 h. EtOH was removed under reduced pressure. H2O (40 ml) was added to the residue, and the resulting solution was extracted with EtOAc (3*40 ml). The EtOAc of the combined organic layer was removed by rotary evaporation under reduced pressure to yield 1-(phenyl)-butanone oxime (5.5 g) as a pale yellowish solid. |
With ammonium hydroxide hydrochloride; sodium acetate In ethanol; water at 20℃; for 5h; | ||
With hydroxylamine hydrochloride; sodium acetate In ethanol; water for 1h; Reflux; | ||
With hydroxylamine hydrochloride; sodium acetate In ethanol; water at 100℃; | ||
With hydroxylamine hydrochloride; sodium ethanolate In methanol at 60℃; | ||
With hydroxylamine hydrochloride; sodium acetate In ethanol; water at 100℃; | ||
With hydroxylamine hydrochloride; potassium carbonate In ethanol at 60℃; for 1h; | ||
5.5 g | With hydroxylamine hydrochloride; sodium acetate In ethanol at 60℃; for 6h; | 87.1 First step 1-phenylbutanone (5 g), hydroxylamine hydrochloride (4.66 g) and anhydrous sodium acetate (11.07 g) were weighed, dissolved together in ethanol (80 ml)Mixer reaction at 60 °C for 6 h. The solvent of the reaction solution was collected, suspended and dissolved with water (40 ml), and extracted from ethyl acetate (40 mL '3), and the solvent was recovered with an ethyl acetate layer to obtain a pale yellow solid 1-phenylbutanone oxime 5.5 g) was obtained. |
With hydroxylamine hydrochloride; sodium acetate In ethanol; water at 100℃; for 6h; | ||
With hydroxylamine hydrochloride; sodium acetate In ethanol; water Reflux; Inert atmosphere; Schlenk technique; | ||
With pyridine; hydroxylamine hydrochloride In ethanol at 60℃; for 1h; | Typical procedure for preparation of ketoxime carboxylates General procedure: To a solution of ketone (22.0 mmol) and pyridine (5.0 mL, 61.8 mmol) in EtOH (10 mL) was added NH2OH•HCl (2.29 g, 33.0 mmol) in one portion and the reaction mixture was stirred at 60 oC for 1h. Upon completion of the reaction as indicated by TLC, the reaction mixture was quenched by adding water and the organic materials were extracted twice with ethyl acetate. Organic phase was washed with 1N aqueous HCl and saturated salt water, dried over MgSO4. The solvent was removed in vacuo to give oximes. The above crude product was treated with Ac2O (4.2 mL, 44.4 mmol) and a catalytic amount of 4-dimethylaminopyridine (5 mg) in pyridine (10 mL) and the reaction mixture was stirred at room temperature for 1 h. Upon completion of the reaction as indicated by TLC, the reaction mixture was treated by water, and the organic materials were extracted twice with ethyl acetate. Organic phase was washed with 1N aqueous HCl and saturated salt water, dried over MgSO4. The solvent was removed in vacuo to give ketoxime carboxylates. The crude product was purified by recrystallization from ethyl acetate-hexane. | |
With pyridine; hydroxylamine hydrochloride In methanol at 20℃; | ||
With hydroxylamine hydrochloride; sodium acetate In ethanol; water at 95℃; for 2h; | ||
With hydroxylamine hydrochloride; sodium acetate In ethanol; water for 1.5h; Reflux; | ||
With hydroxylamine hydrochloride; sodium acetate In ethanol at 95℃; Inert atmosphere; Glovebox; | ||
With hydroxylamine hydrochloride; sodium acetate In ethanol at 80℃; | ||
With hydroxylamine hydrochloride; sodium acetate In ethanol | ||
80 % de | With hydroxylamine hydrochloride; sodium acetate In ethanol; water Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With Tetrahydrofurfuryl alcohol; sodium tetrahydridoborate; ethanol; (S,S)-(β-oxoaldiminato)cobalt(II) In chloroform at -20℃; for 12h; | |
99% | Stage #1: propiophenone With C44H44CuN2P2(1+)*F6P(1-) In toluene at 25℃; for 1h; Inert atmosphere; Stage #2: With sodium hydroxide In methanol; lithium hydroxide monohydrate Inert atmosphere; | 3. Typical procedure for catalytic hydrosilylation of ketones General procedure: Under nitrogen atmosphere the copper based catalyst 1 (8 7 mmg0.01 mmol), tBuOK ( 5 6 mmg0.05 mmol) and toluene (3 mL) were placed in a tube equipped with a Teflon coated magnetic stirring bar. T he mixture was stirred at 25 °C for 15 min and then polymethylhydrosiloxane (PMHS, 0.0 9 m L, 1.5 mmol mmol) was injected. After 15mins, ketone (0.5 mmol) was introduced and the mixture was stirred at 25 °C for therequired reaction time. The mixture was quenched with MeOH (1 mL) and 10%NaOH solution (3 mL), and the mixture was stirred for 4 h. T he mixture was extractedwith ethyl acetate (5 mL × 3) and the combined organic layer was washed with waterand saturated sodium chloride solution, dried over anhydrous Na2SO4. the solvent was removed under vacuum and the residue was purified by flash chromatography (silica gel) to afford the desired product. All the product alcohols were analyzed by 1H NMR, 13C NMR, or GC analysis. |
96.2% | With sodium tetrahydridoborate In ethanol for 5h; |
96% | With C44H40ClN2NiP2(1+)*F6P(1-); hydrogen; potassium hydroxide In isopropanol at 120℃; for 12h; Autoclave; | 3. Typical procedure for hydrogenation General procedure: Ni-based catalyst (0.01 mmol) was added into a dried autoclave (100 mL). After the addition of fresh distilled iPrOH (20 mL), the autoclave was purged with H2 (30 bar) five times. The mixture was then stirred under 30 bar H2 for 1 h. After releasing the H2 gas in a fumehood, KOH in iPrOH (1 M, 0.2 mL) and ketone (0.5 mmol) were sequentially introduced through an injection port. The autoclave was then pressurized to 40 bar H2 and the reaction mixture stirred at 120 °C for 12 h. After cooling down to room temperature and subsequently releasing the H2 pressure in a fumehood, the mixture was concentrated and purified by chromatograph on a silica-gel column. The conversion of the product was determined by GC. |
95% | With phenyl trimethylsilyl telluride In methanol; benzene for 3h; Ambient temperature; | |
94% | With sodium tetrahydridoborate In tetrahydrofuran for 1.17h; Heating; | |
94% | With Cp*Ir(6,6'-dionato-2,2'-bipyridine)(H2O); hydrogen In tert-Amyl alcohol at 30℃; for 12h; Green chemistry; | 4.2. General procedure for catalytic hydrogenation of 2 General procedure: To an oven-dried 5 mL round-bottom flask were added ketone (1 mmol), cat. 7 (2.7 mg, 0.5 mol %) and tert-amyl alcohol (1 mL). Next, vacuum was applied to the flask followed by filling with H2 gas and keeping the flask attached to a balloon filled with H2 gas. The mixture was heated at 30 °C for 12 h. After completion of the reaction, the solvent was removed by evaporation under reduced pressure. The alcohols were isolated and purified by filtering a hexanes/ethyl acetate (5:1) solution of the crude product through a pad of silica gel, and then removing the solvent under reduced pressure. The conversion and purity of the alcohol products was assessed using NMR spectroscopy. |
94% | With [Cp*Ir(2,2'-bpyO)(OH)][Na]; hydrogen In lithium hydroxide monohydrate at 30℃; for 12h; Green chemistry; | 4.1. General procedure for catalytic hydrogenation of ketones,aldehydes or unsaturated aldehydes General procedure: To an oven-dried 5 mL round-bottom flask were added ketonesor aldehydes or unsaturated aldehydes (1 mmol), cat. 6 (5.5 mg,1 mol %) and H2O (1 mL). Next, vacuum was applied to the flask followedby filling with H2 gas and keeping the flask attached to a balloonfilled with H2 gas. The mixture was heated at 30 °C for 12 h.After completion of the reaction, the mixture was extracted withethyl acetate (5 mL x 3). Then, the ethyl acetate layers were combined, dried with anhydrous sodium sulfate, filtered, and concentratedby evaporation under reduced pressure. The alcohols wereisolated and purified by filtering a hexanes/ethyl acetate (8:1)solution of the crude product through a pad of silica gel. Thenthe solvent was removed under reduced pressure to afford the correspondingproducts. The purity of alcohol products was assessedusing 1H NMR spectroscopy. |
93% | With sodium tetrahydridoborate; sodium hydroxide In methanol at 0 - 20℃; | |
93% | With Cp*Ir(6,6'-dionato-2,2'-bipyridine)(H2O); isopropanol In lithium hydroxide monohydrate at 82℃; for 6h; Inert atmosphere; Schlenk technique; chemoselective reaction; | |
93% | With sodium tetrahydridoborate In ethanol at 20℃; for 36h; | |
93% | With Cp*Ir(6,6'-dionato-2,2'-bipyridine)(H2O); isopropanol at 82℃; for 6h; Inert atmosphere; Green chemistry; | 21 1-Phenylbutan-1-ol The 1 - phenylethyl butanone (148 mg, 1.0 mmol), cat. [Ir] (1.1 mg, 0 . 002 mmol, 0.2 μM %) and isopropyl alcohol (5 ml) are added to the 25 ml Kjeldahl tube, N2Protection Cooling to room temperature, rotary evaporation to remove the solvent, then through the column chromatography (developing solvent: petroleum ether/ethyl acetate) to obtain the pure target compound, yield: 93% |
92% | With [Cp*Ir(2,2'-bpyO)(OH)][Na]; hydrogen In lithium hydroxide monohydrate at 30℃; for 12h; | 19 The method is: Phenretones (148 mg, 1.0 mmol), metal ruthenium complex [Cp*Ir(2,2'-bpyO)(OH)][Na] (4.6 mg, 0.01 mmol, 1 mol%) and water (1 mL) is added to 25 ml round bottom flask, and the air in the round bottom flask is replaced with hydrogen. The pressure of hydrogen gas in the system during the entire process of the reaction was 1 standard atmospheric pressure, and the reaction mixture was reacted at 30 °C, the hydrogen atmosphere was 12 h. After the reaction, the solvent was removed by rotary evaporation, and then the pure target compound was obtained by column chromatography (eluent: petroleum ether / ethyl acetate = 10:1), yield: 92%. |
91% | With isopropanol; potassium hydroxide at 80℃; for 16h; Schlenk technique; | |
90% | With sodium tetrahydridoborate; Montmorillonite K10 In hexane at 20℃; for 1h; | |
90% | With C12H19ClCoN5(1+)*Cl(1-); sodium tertiary butoxide In isopropanol at 85℃; for 24h; Inert atmosphere; | |
89% | With sodium tetrahydridoborate; nickel (II) chloride In tetrahydrofuran at 20℃; for 0.25h; | |
88% | With CdS(x)Se(1-x) x:0-1;; caesium acetate; para-thiocresol In toluene for 16h; Sealed tube; Inert atmosphere; Irradiation; | |
87% | With sodium tetrahydridoborate In methanol at 20℃; for 4h; | 4.2.1 1-Phenyl-1-butanol, rac-3a General procedure: For a typical reaction, NaBH4 (1.0g, 26.8mmol) was added to a stirred solution of 1-pentanophenone (4.4g, 26.8mmol) in dry methanol (30mL). The exotherm was controlled by an ice bath. The suspension was stirred at room temperature for 4h, monitored by TLC. After the reaction was quenched by an addition of water (20mL), the methanol was removed under vacuum and the residue was extracted with ethyl acetate (3×30mL). The combined organic phases were washed with brine (20mL), dried over MgSO4 and then filtered. The organic solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (hexane/ethyl acetate, 3:1) to give rac-4a (3.8g, 83%). The 1H NMR spectra of alcohols 3a,24 4a,24 5a,24 6a,24 7a,25 8a,26 9a,27 were all in agreement with those reported in the literature. 4.2.1 1-Phenyl-1-butanol, rac-3a (0020) Colorless oil (2.2g, 87%). 1H NMR (400MHz, CDCl3) δ 0.93 (t, J=7.4Hz, 3H, CH3), 1.26-1.47 (m, 2H, CH2CH3), 1.63-1.83 (m, 2H, CHCH2), 1.92 (br s, 1H, OH), 4.66 (dd, J=6.0, 7.6Hz, 1H, CH), 7.25-7.34 (m, 5H, Ph). |
87% | With methanol; [Cp*Ir(2,2'-bpyO)(OH)][Na] at 66℃; for 12h; Inert atmosphere; Schlenk technique; | |
85% | With [2,2]bipyridinyl; sodium hypophosphite monohydrate; di-μ-chlorobis-[(η6-p-cymene)chlororuthenium(II)] In lithium hydroxide monohydrate at 80℃; for 24h; Inert atmosphere; Sealed tube; | |
78% | With C12H12MnO4(1+)*BF4(1-); potassium-t-butoxide In isopropanol at 90℃; for 48h; Schlenk technique; Inert atmosphere; | |
73% | With isopropanol In tetrahydrofuran at 76℃; for 1h; | |
66% | With bis[chlorido(η2,η2-cycloocta-1,5-diene)rhodium(I)]; anhydrous potassium trifluoroacetate; C21H29P; 4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl-4',4',5',5'-tetramethyl-1,3,2-dioxaborolane; 4,4,5,5-tetramethyl-1,3,2-dioxaborolane In tetrahydrofuran; cyclohexane at 20℃; for 24h; regioselective reaction; | |
60% | With bromo(propan-2-yl)magnesium In diethyl ether at 20 - 30℃; for 4h; | |
52% | With 4,4'-di-tert-butylbiphenyl; lithium; isopropanol In tetrahydrofuran at 76℃; for 4h; | |
7% | With Geotrichum candidum IFO 4597 cells In lithium hydroxide monohydrate | |
7% | With rac-octan-2-ol; magnesium(II) oxide at 179.85℃; for 6h; | |
With ethanol; nickel at 95 - 150℃; Hydrogenation; | ||
With ethanol; copper oxide-chromium oxide at 95 - 150℃; Hydrogenation; | ||
With ethanol; natrium | ||
With copper oxide-chromium oxide at 120 - 130℃; Hydrogenation; | ||
With triethylsilane; perchloric acid In acetonitrile at 24.9℃; | ||
With perchloric acid In acetonitrile at 57.9℃; kinetic isotope effects also investigated with AcrH2-CD3 and AcrD2; | ||
With potassium hydroxide; phosphinerhodium; isopropanol at 82℃; for 53h; hydrogen transfer reduction using various chiral catalysts, various optical yields; | ||
With 1,2-bis(3,5-di-t-butylsalicyl)benzene; tris(methyl)aluminum; diisobutylaluminium hydride In diethyl ether; dichloromethane at -78℃; for 1h; relative reactivity (vs acetophenone); | ||
With (+)-tris<(S)-2-methylbutyl>aluminium etherate In benzene | ||
With sodium hydroxide; sodium tetrahydridoborate In methanol | ||
With potassium hydroxide In methanol at 128℃; | ||
With NB-Enantride In tetrahydrofuran; diethyl ether; n-Pentane at -100℃; for 3h; | ||
100 % Chromat. | With diisopinocamphenylchloroborane | |
With perchloric acid In acetonitrile at 331℃; | ||
With lithium aluminium hydride | ||
With triethylsilane; perchloric acid In acetonitrile at 24.9℃; | ||
With diphenylsilane; sodium hydride; potassium carbonate 1.) 0 deg C, 1 h, 20 deg C, 24 h, 2.) hydrolysis; Yield given. Multistep reaction; | ||
With potassium phosphate buffer; pig testicular 20β-hydroxysteroid dehydrogenase; NADPH at 37℃; | ||
With sodium tetrahydridoborate | ||
With sodium tetrahydridoborate In methanol | ||
With sodium tetrahydridoborate | ||
With ketoreductase; isopropanol In phosphate buffer; n-Pentane at 24.99℃; | ||
With sodium tetrahydridoborate In ethanol | ||
Stage #1: propiophenone With [(Cp*)Rh(Cl)(κ2-3-PiPr2-2-S-indene)]; phenylsilane; lithium tetrakis(pentafluorophenyl)borate In tetrahydrofuran at 20℃; for 5h; Stage #2: With hydrogenchloride In tetrahydrofuran; lithium hydroxide monohydrate; propan-2-one at 0 - 20℃; for 2.5h; | ||
With [Ir(cod)(κ2-o-tBu2P-C6H4-NMe2)](+)PF6(-); isopropanol; sodium tertiary butoxide at 82℃; for 0.5h; Inert atmosphere; | ||
With sodium tetrahydridoborate | ||
With methanol; sodium tetrahydridoborate at 0 - 20℃; | ||
39 %Spectr. | With methanol; sodium tetrahydridoborate In diethyl ether at 30℃; for 1h; | |
With sodium tetrahydridoborate In methanol at 20℃; for 2.5h; | ||
With sodium tetrahydridoborate In methanol Inert atmosphere; | ||
With Triethoxysilane at 20℃; for 0.5h; Neat (no solvent); | ||
With Ru(Ph2PNHCH2-C4H3O)(η-6-benzene)Cl2; isopropanol; potassium hydroxide at 82℃; for 0.333333h; | ||
With sodium tetrahydridoborate In ethanol at 100℃; for 0.0166667h; Microwave irradiation; | ||
With sodium tetrahydridoborate In ethanol Inert atmosphere; | ||
With [C10H6N2{NHPPh2Ru(η6-benzene)Cl2}2]; sodium hydroxide In isopropanol for 0.333333h; Reflux; Inert atmosphere; | 4.3.4 General procedure for the transfer hydrogenation of ketones General procedure: Typical procedure for the catalytic hydrogen transfer reaction: a solution of complexes [C10H6N2{NHPPh2Ru(η6-benzene)Cl2}2], 1, [C10H6N2{PPh2NHRh(cod)Cl}2], 2 and [C10H6N2{NHPPh2Ir(η5-C5Me5)Cl2}2], 3 (0.005 mmol), NaOH (0.025 mmol) and the corresponding ketone (0.5 mmol) in degassed iso-PrOH (5 mL) were refluxed for 10 min for 1, 1 h for 2 and 3 h for 3. After this period a sample of the reaction mixture was taken off, diluted with acetone and analyzed immediately by GC. Conversions obtained are related to the residual unreacted ketone. | |
With [Rh((Ph2P)2NCH2-C4H3S)(Cp*)Cl]Cl; sodium hydroxide In isopropanol at 82℃; for 6h; Schlenk technique; Inert atmosphere; | ||
Stage #1: propiophenone With sodium tetrahydridoborate In methanol at 0℃; Stage #2: With hydrogenchloride In methanol; lithium hydroxide monohydrate | ||
With [Ru(Cy2PNHCH2-C4H3O)(η6-benzene)Cl2]; isopropanol; sodium hydroxide at 82℃; for 4h; Inert atmosphere; Schlenk technique; | ||
With [Rh(Cy2PNHCH2-C4H3O)(cod)Cl]; isopropanol; sodium hydroxide at 82℃; for 0.5h; Inert atmosphere; Schlenk technique; | 4.2. General procedure for the transfer hydrogenation of ketones General procedure: Typical procedure for the catalytic hydrogen transfer reaction: a solution of complexes [Rh(Cy2PNHCH2-C4H3O)(cod)Cl], (1),[Rh(Cy2PNHCH2-C4H3S)(cod)Cl], (2), [Ir(Cy2PNHCH2-C4H3O)(η5-C5Me5)Cl2], (3) and [Ir(Cy2PNHCH2-C4H3S)(η5-C5Me5)Cl2], (4)(0.005 mmol), NaOH (0.025 mmol) and the corresponding ketone(0.5 mmol) in degassed iso-PrOH (5 mL) were refluxed until the reactions were completed. After this period a sample of the reactionmixture was taken off, diluted with acetone and analyzed immediately by GC. Conversions obtained are related to the residual unreacted ketone. | |
With [Ru((Ph2PO)-C7H14N2Cl)(η6-benzene)Cl2]Cl; potassium hydroxide In isopropanol at 82℃; for 1h; Inert atmosphere; Schlenk technique; | 3.2 Transfer hydrogenation of ketones General procedure: Typical procedure for the catalytic hydrogen transfer reaction: a solution of the complexes [Ru((Ph2PO)-C7H14N2Cl)(η6-arene)Cl2]Cl and [Ru((Ph2PO)-C7H14N2Cl)(η6-arene)Cl2]Cl {arene: benzene 4, 5; p-cymene 6, 7} (0.005 mmol), KOH (0.025 mmol) and the corresponding ketone (0.5 mmol) in degassed 2-propanol (5 mL) was refluxed until the reactions were completed. Then, a sample of the reaction mixture was taken off, diluted with acetone and analyzed immediately by GC. The conversions are related to the residual unreacted ketone. GC analyses were performed a Shimadzu 2010 Plus Gas Chromatograph equipped with a capillary column (5 % biphenyl, 95 % dimethylsiloxane) (30 m×0.32 mm×0.25 μm). The GC parameters for transfer hydrogenation of the ketones were as follows: initial temperature, 50° C; initial time, hold min 1 min; solvent delay, 4.48 min; temperature ramp 15° C/min; final temperature, 270° C, hold min 5 min; final time, 20.67 min; injector port temperature, 200° C; detector temperature, 200° C, injection volume, 2.0 μL | |
85 %Spectr. | With C36H103AlO4Si14; isopropanol In neat (no solvent) at 50℃; for 24h; Glovebox; Schlenk technique; | |
With [(ruthenium(II))3(2-[(diphenylphosphanyl)({2-[(diphenylphosphanyl)oxy]ethyl})amino]-ethyldiphenylphosphinite)(η6-p-cymene)3Cl6]; isopropanol; sodium hydroxide at 82℃; for 0.5h; Reflux; | ||
With [(ruthenium(II))3(2-[(diphenylphosphanyl)({2-[(diphenylphosphanyl)oxy]ethyl})amino]-ethyldiphenylphosphinite)(η6-p-cymene)3Cl6]; isopropanol; sodium hydroxide at 82℃; Inert atmosphere; Schlenk technique; | ||
With [Ru(2,2'-bipyridine)2(1,5-dihydro-2H-cyclopenta[1,2-b:5,4-b′]dipyridine-2-one)](PF6)2; isopropanol; sodium hydroxide at 82℃; for 7h; | 2.2 General procedure for the transfer hydrogenation of ketones General procedure: A typical procedure for the catalytic hydrogen transfer reaction was as follows: A solution of the complex [Ru(bpy)2L](PF6)2], NaOH (0.025mmol) and the corresponding ketone (0.5mmol) in degassed iso-Pr-OH (5mL) were refluxed until the completion of the reaction. After this period, a sample of the reaction mixture was taken, diluted with acetone and analyzed immediately by GC. Conversions obtained were related to the residual unreacted ketone. The GC parameters were as follows: initial temperature, 110°C; initial time, 1min; solvent delay, 4.48min; temperature ramp 80°C/min; final temperature, 200°C; final time, 21.13min; injector port temperature, 200°C; detector temperature, 200°C; injection volume, 2.0μL. | |
With anti-Prelog short-chain dehydrogenase/reductase EbSDR8 from Empedobacter brevis ZJUY-1401; isopropanol; NADH In aq. phosphate buffer at 35℃; for 4h; Enzymatic reaction; | ||
With C37H65ClN3O2RuS(1+)*Cl(1-); anhydrous sodium formate In lithium hydroxide monohydrate at 60℃; Schlenk technique; Inert atmosphere; | ||
With C38H38IrN4S2(1+)*F6P(1-); ammsnium formate; 3-methyl-5-p-methoxyphenyl-1-hydropyrazole In tetrahydrofuran; lithium hydroxide monohydrate at 40℃; | ||
With iso-butanol; sodium hydroxide at 80℃; for 3h; | ||
99 %Chromat. | With trans-RuCl(2-(2-pyridyl-6-ol)-1,10-phenanthroline)(PPh3)2PF6; potassium-t-butoxide; isopropanol at 80℃; for 0.5h; Inert atmosphere; Schlenk technique; | |
> 99 %Chromat. | With (4-NHCpr)Triaz(NHP<SUP>i</SUP>Pr<SUB>2</SUB>)<SUB>2</SUB>Mn(CO)<SUB>2</SUB>Br; potassium-t-butoxide; hydrogen In toluene at 80℃; for 4h; Inert atmosphere; Autoclave; | |
Multi-step reaction with 2 steps 1: C27H44AlN3 / 4 h / 20 °C / Inert atmosphere; Glovebox 2: mesoporous silica / Inert atmosphere; Heating | ||
With C27H33Cl2N2OPRh(1+)*Cl(1-); isopropanol; sodium hydroxide for 1h; Inert atmosphere; Schlenk technique; | 2.2 Transfer hydrogenation of ketones General procedure: Typical procedure for the catalytic hydrogen transfer reaction: a solution of cataysts (1-chloro-3-(3-methylimidazolidin-1-yl)propan-2-yl diphenylphosphinite chloride) (chloro 4-1,5-cyclooctadiene rhodium(I))], 2 or (1-chloro-3-(3-methylimidazolidin-1-yl)propan-2-yl diphenylphosphinite chloride) (dichloro 5-pentamethylcyclopentadienyl iridium(III))], 3 (0.005mmol), NaOH (0.025mmol) and the corresponding ketone (0.5mmol) in degassed 2-propanol (5mL) were refluxed until the reactions were completed. Then, a sample of the reaction mixture was taken off, diluted with acetone and analyzed immediately by GC. The conversions are related to the residual unreacted ketone. GC analyses were performed on a Shimadzu 2010 Plus Gas Chromatograph equipped with capillary column (5% biphenyl, 95% dimethylsiloxane) (30m×0.32mm×0.25μm). The GC parameters for transfer hydrogenation of ketones were as follows; initial temperature, 50°C; initial time, hold min 1min; solvent delay, 4.48min; temperature ramp 15 °C/min; final temperature, 270°C, hold min 5min; final time, 20.67min; injector port temperature, 200°C; detector temperature, 200°C, injection volume, 2.0μL. | |
With sodium hydroxide; phenylboronic acid In isopropanol at 82℃; | 2.3. Transfer hydrogenation of acetophenone by BL1 and BL2 General procedure: The common procedure for transfer hydrogenation: particular amount of (0.04 mmol) boroncomplex solutions, NaOH (0.05 mmol), and acetophenone (5 mmol) in degassed isoPrOH(5 mL) were reuxed at 82 °C. Samples from the mixture were taken, diluted with acetoneand checked for conversion at dierent time periods. The products were compared with theunreacted acetophenone. GC analyses were applied with a Shimadzu 2010 Plus GasChromatograph having a capillary column (95% dimethyl siloxane and 5% biphenyl)(30 m × 0.32 mm × 0.25 m). The adjusted GC parameters were: initial temperature, 50 °C;solvent delay, 4.48 min; initial time, hold 1 min; nal temperature, 270 °C; hold 5 min; temperatureramp 15 °C min-1; injector port temperature, 200 °C; detector temperature, 200 °C,nal time, 20.67 min, and injection volume, 1.5 L. | |
With methanol; sodium tetrahydridoborate at 20℃; | ||
With hydrogen In isopropanol at 65℃; for 3h; Autoclave; chemoselective reaction; | ||
With sodium tetrahydridoborate | ||
Multi-step reaction with 2 steps 1: C84H108Cl2N10Pd2 / 12 h / 60 °C 2: mesoporous silica; methanol / 6 h / 60 °C | ||
With methanol; sodium tetrahydridoborate at 20℃; for 1h; | ||
With sodium tetrahydridoborate; ethanol at 0 - 20℃; Inert atmosphere; Schlenk technique; | ||
With sodium tetrahydridoborate; ethanol at 20℃; for 16h; Inert atmosphere; | ||
99 %Chromat. | With sodium methoxide; C27H25Cl2NORu; isopropanol at 80℃; for 12h; Schlenk technique; Inert atmosphere; | |
30 %Spectr. | With potassium isopropoxide; [UO2(OTf)2]; isopropanol at 80℃; for 15h; Inert atmosphere; Schlenk technique; | |
With C24H33BO2; isopropanol; sodium hydroxide at 82℃; for 9h; Inert atmosphere; Sealed tube; | 2.4 General procedure for transfer hydrogenation of ketones with boronate ester catalysts General procedure: The trigonal-planar or tetrahedral catechol boronate ester catalysts (0.005mmol), NaOH (0.025mmol), and the corresponding ketone (0.5mmol) were weighed into a Teflon septum-sealed vial (reaction flask) in an inert atmosphere conditions in degassed isoPrOH (5.0mL), and then a sample of the reaction mixture is taken off, diluted with acetone, and analyzed immediately by GC; conversions obtained are related to the residual unreacted ketone. | |
With methanol; sodium tetrahydridoborate at 0 - 20℃; Inert atmosphere; | ||
With [dichloro(η4-pentamethylcyclopentadienyl)(1-furan-2-ylethyldiphenylphosphinite)iridium(III)]; potassium hydroxide In isopropanol at 82℃; for 3h; | 2.3. General procedure for the transfer hydrogenation of ketones General procedure: A typical procedure for the catalytic hydrogen transfer reaction is given below: a solutionof pre-catalysts (2-5) (0.0025mmol), KOH (0.0125mmol), and the respective ketone(0.5mmol) in degassed 2-propanol (5mL) was refluxed until the reactions were completed.Then, a sample of the reaction mixture was taken off, diluted with acetone, and analyzedimmediately by GC. The conversions are related to the residual unreacted ketone. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With bromine at 20℃; for 0.333333h; | |
95% | With Oxalyl bromide In dichloromethane; dimethyl sulfoxide at -10 - 30℃; for 0.666667h; Inert atmosphere; | 1 (1) Preparation of 2-bromo-1-phenyl-1-butanone Nitrogen protection, in a 100 mL three-necked flask equipped with a thermometer,Add oxalyl bromide (7.5 mmol, 1.1 mL,1.5 equiv) and anhydrous dichloromethane (10 mL).Slowly add dimethyl sulfoxide (7.5 mmol, dropwise) at a constant pressure dropping funnel at -10 °C.A solution of 0.53 mL, 1.5 equiv) in anhydrous dichloromethane (10 mL).After the addition was completed, stirring was continued for 10 min at -10 °C.A solution of phenylbutanone (5 mmol, 740 mg, 1.0 equiv) in dry dichloromethane (10 mL) was then evaporated.After the addition was completed, stirring was continued for 10 min at -10 °C.Then slowly heat to 30 ° C, the reaction was 0.5 h.Ice bath at 0 ° C,Add 30mL of distilled water,Dispensing, taking the organic phase,Wash with saturated aqueous sodium chloride (50 mL).Dry over anhydrous sodium sulfate.filter,The solvent was evaporated to give 2-bromo-1-phenyl-1-butanone 1.07 g.The yield was 95%. |
95% | With Oxalyl bromide; dimethyl sulfoxide In dichloromethane at -10 - 30℃; for 0.5h; Inert atmosphere; | Bromination of Alkenes, Alkynes and Ketones; General Procedure General procedure: To a solution of (COBr)2 (0.43 mL, 3.0 mmol, 1.5 equiv) in CH2Cl2 (10mL) at -10 °C was added dropwise a solution of DMSO (0.21 mL, 3.0mmol, 1.5 equiv) in CH2Cl2 (10 mL) under an atmosphere of nitrogen. After 10 min, a solution of alkene, alkyne or ketone (2 mmol, 1.0 equiv) in CH2Cl2 (5 mL) was added. The mixture was then allowed to warm to 20-40 °C and stirred for 0.5-3 h. Distilled H2O (20 mL) was added dropwise at 0 °C. After stirring for 10 min, the organic layer was separated and washed with brine (2 × 20 mL), dried (Na2SO4), filtered and concentrated under vacuum to afford the brominated product. Most products can be obtained in high purity without further purification, except 3n, 7d, and 7f. The three products need purification by flash chromatography (silica gel, PE/EtOAc = 10:1 for 3n, PE/EtOAc= 60:1 for 7d, PE/EtOAc = 20:1 for 7f). |
94% | With hydrogen bromide; dimethyl sulfoxide In water; ethyl acetate at 60℃; for 6h; | |
93% | With benzyltrimethylammonium tribromide In methanol; dichloromethane Heating; | |
92% | With aluminium trichloride; bromine In diethyl ether | |
92% | With bromine In tetrahydrofuran; hexane at 5 - 15℃; for 1h; | 3 REFERENCE EXAMPLE 3 Synthesis of 1-phenyl-2-bromo-1-butanone To a tetrahydrofuran solution (20 mL) of 9.917 g (67.0 mmol) of butyrophenone, a hexane solution (10 mL) of 11.78 g (1.1 equivalents) of bromine was gradually added at 5°C. The temperature was elevated to 15°C, and the solution was stirred for 1 hour. To the solution, 20 mL of water and 40 mL of ethyl acetate were added to conduct extraction. The organic layer was washed with 30 mL of a saturated sodium hydrogen carbonate solution three times, dried over anhydrous magnesium sulfate, and subjected to distillation under a reduced pressure to remove the solvents. 1-Phenyl-2-bromo-1-butanone was obtained as a light peach-colored oily substance (23.94 g, crude yield: 92%). |
88% | Stage #1: propiophenone With [hydroxy(tosyloxy)iodo]benzene for 0.025h; microwave irradiation; Stage #2: With magnesium bromide for 0.0333333h; microwave irradiation; Further stages.; | |
84% | With copper(ll) bromide In dichloromethane; ethyl acetate for 18h; Reflux; Inert atmosphere; | 4.2. A representative synthetic procedure of skeletons 3 and 6 is as follows General procedure: Copper(II) bromide (CuBr2, 268 mg, 1.2 mmol) was added to a solution of skeleton 5 (1.0 mmol) in the co-solvent of EtOAc and CH2Cl2 (1:1, 20 mL), at 25 °C. The reaction mixture was stirred at reflux for 18 h. The reaction mixture was cooled to 25 °C. Saturated NaHCO3 (5 mL) was added to the reaction mixture and the solvent was concentrated. The residue was diluted with water (10 mL) and the mixture was extracted with EtOAc (3 x 20 mL). The combined organic layers were washed with brine, dried, filtered and evaporated to afford crude product. Purification on silica gel (hexanes/EtOAc = 10/1-6/1) afforded skeletons 3 and 6. |
70% | With bromine In diethyl ether for 0.5h; Inert atmosphere; | |
With bromine; benzene | ||
With chloroform; bromine | ||
With carbon disulfide; bromine | ||
With tetrachloromethane; bromine | ||
With diethyl ether; bromine | ||
With diethyl ether; phosphorus pentabromide at 40 - 50℃; | ||
With bromine In tetrachloromethane for 0.5h; Ambient temperature; | ||
With 1,4-dioxane; bromine at 25℃; for 16h; | ||
With hydrogen bromide; bromine In acetic acid | ||
With bromine In diethyl ether | ||
With bromine In dichloromethane at 20℃; Inert atmosphere; | ||
With bromine In diethyl ether at 20℃; Inert atmosphere; | ||
With bromine In dichloromethane at 0 - 20℃; for 0.5h; | ||
With copper(ll) bromide | ||
With copper(ll) bromide In ethanol at 78℃; | ||
With bromine In dichloromethane | ||
With copper(ll) bromide | ||
With bromine In dichloromethane for 2h; | ||
With bromine In dichloromethane for 0.25h; | ||
With bromine In diethyl ether at 20℃; Schlenk technique; Inert atmosphere; | Synthesis of α-bromoketones (SM): General procedure: General experimental procedure A (GEP-A): To an oven-dried Schlenk flask were added 1 equiv (10 mmol) of the corresponding ketone and anhydrous Et2O under nitrogen. Then, 1 equiv of Br2 was added and it was allowed to react overnight at r.t. The reaction was quenched with an aqueous Na2S2O3 solution (10 mL). The extraction was carried out with brine (10 mL) and diethyl ether (3 × 10 mL). The organic layers were combined and dried over anhydrous Na2SO4. The solvent was removed with a rotatory evaporator under reduced pressure obtaining α-bromo ketones SM that were used in the next step without further purification. Ketones SM1 (desyl chloride) and SM2 (α-bromopropiophenone) are commercially available. Spectroscopic data of α-bromoketones SM3-6 are in agreement with those found in the literature.1 | |
With bromine In diethyl ether at 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With Cumene hydroperoxide at 120℃; for 20h; Yield given. Further byproducts given. Yields of byproduct given; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With Cumene hydroperoxide at 120℃; for 20h; other concentrations of cumene hydroperoxide; reaction of other phenyl cycloalkanes, also with tert-butyl hydroperoxide; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With water In neat (no solvent) at 100℃; for 22h; Green chemistry; regioselective reaction; | General procedure for hydration of alkynes General procedure: Reactions were performed in a magnetically stirred round bot-tomed flask fitted with a condenser and placed in a temperature controlled oil bath. Zeolite (H) (100 mg) was added to the well stirred solution of alkyne (2 mmol) and H2O (8 mmol) and the reac-tion mixture was allowed to stir at 100 °C. After disappearance of the alkyne (monitored by TLC) or after an appropriate time, the reaction mixture was cooled to room temperature, diluted with ethyl acetate. The catalyst was separated by filtration and the removal of solvent in vacuo yielded residue. and it was further puri-fied by column chromatography using silica gel (100-200 mesh) to afford pure products. All the products were identified on the basisof H1 and C13NMR spectral data. |
92% | With iron(III) chloride; water; silver(I) triflimide In 1,4-dioxane at 95℃; for 60h; regioselective reaction; | |
92% | With trifluorormethanesulfonic acid; water In 2,2,2-trifluoroethanol at 25℃; for 45h; Sealed tube; regioselective reaction; |
88% | With tropylium tetrafluoroborate; water; acetic acid at 130℃; for 48h; Inert atmosphere; | |
87% | With p-toluenesulfonic acid monohydrate; acetic acid In dichloromethane at 80℃; for 20h; Sealed tube; | General procedures for alkyne hydration General procedure: The corresponding alkyne (1 mmol) was added to a solution of p-toluenesulfonic acidmonohydrate (1 mmol, 0.190 g), acetic acid (0.5 mL) in CH2Cl2 (1.0 mL). Thereaction was then sealed and stirred at the indicated temperature (oC) and for theindicated amount of times (h) in Table 2. After completion, saturated aqueousNaHCO3 (10 mL) was added to quench the reaction and then extracted with CH2Cl2(10 mL×3). The organic layer was dried over Na2SO4 and concentrated in vacuo. Theresidue was purified by column chromatography to give the pure product. Forsubstrates 1j. 1l, 1n, 1p and 1q, DCE was used as solvent in consideration ofoperation convenience. |
81% | With indium(III) triflate; water; toluene-4-sulfonic acid In 1,2-dichloro-ethane for 14h; Sealed tube; Reflux; regioselective reaction; | 6.20 4.2 General procedure for the hydration of alkynes 1a-1n and 1p-1t General procedure: The reaction mixture of In(OTf)3 (11.2 mg, 2 mol %), PTSA (57.1 mg, 30 mol %), DCE (2.0 mL), alkynes 1a-1n or 1p-1t (1.0 mmol) and water (0.2 mL) in a 10 mL flask or in a 10 mL sealed tube was stirred at reflux and monitored periodically by TLC. Upon completion, DCE was removed under reduced pressure using an aspirator, and then the residue was purified by flash chromatography (PE/EA) on silica gel to afford corresponding carbonyl compounds 2a-2n or 2p-2t. |
79% | With water In 1,4-dioxane at 80 - 120℃; regioselective reaction; | |
66% | With phosphoric acid; boron trifluoride In acetonitrile; benzene at 60 - 70℃; for 1h; | |
20% | With Ag3STA; water at 100℃; for 14h; neat (no solvent); regioselective reaction; | |
With graphene oxide at 100℃; for 24h; | ||
88 %Chromat. | With iron(III) chloride; water; silver(I) triflimide In 1,4-dioxane-d8 at 120℃; for 20h; regioselective reaction; | |
Multi-step reaction with 2 steps 1: dibromamine-T; water / acetone / 0.17 h 2: water; potassium iodide; sodium sulfite / acetone / 20 °C | ||
With trifluorormethanesulfonic acid; water In 2,2,2-trifluoroethanol at 40℃; for 48h; Inert atmosphere; | ||
With trifluorormethanesulfonic acid; water In 2,2,2-trifluoroethanol at 40℃; for 48h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With indium; acetic acid In tetrahydrofuran Heating; | |
97% | With indium(III) chloride; Bu3SnH4 In methanol at -78 - 20℃; for 1h; | |
93% | With samarium diiodide; 2,4-dichlorophenoxyacetic acid dimethylamine; <i>tert</i>-butyl alcohol In tetrahydrofuran |
86% | With lithium aluminium tetrahydride; (-)-N-methylephedrine; N-ethyl-N-phenylamine In diethyl ether at -78℃; for 3h; | |
84% | With In(OAc)3; phenylsilane In ethanol at 20℃; for 1.5h; | |
83% | With dibutyltin; Dibutyldifluorotin; lithium iodide In tetrahydrofuran at 20℃; | |
72% | With tri-n-butyl-tin hydride; dibutyl tin diiodide In tetrahydrofuran for 2h; Ambient temperature; | |
72% | With N,N,N,N,N,N-hexamethylphosphoric triamide; trichlorosilane In dichloromethane at 0℃; for 0.5h; Inert atmosphere; | |
56% | With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate In benzene at 80℃; for 17h; | |
15% | With indium(III) bromide; water; cyclohexanone In acetonitrile at 0 - 20℃; for 24h; Inert atmosphere; | 4.1 General experimental methods General procedure: To a dry nitrogen-filled 10-mL round-bottomed flask containing InBr3 (0.1mmol) in MeCN (1mL) was added NaOMe (0.12mmol) at rt. The mixture was stirred at room temperature for 30min. To the solution were added MePhSiH2 (1.1mmol), enones 1 (1mmol), carbonyl 2 (1mmol) and MeOH (1mmol) and the resulting mixture was stirred at 0°C for 24h. After quenching with saturated NaCl (aq) (2mL), the reaction mixture was extracted with ether (10mL×2). The combined organic layer was dried over MgSO4 and concentrated. The residue was subjected to column chromatography eluting with hexane/EtOAc. Indium and silane residue were removed by this treatment. The crude product was then purified by flash column chromatography eluted by hexane/EtOAC with gradation mode changing from 9/1 to 3/7. The desired product was obtained at hexane/EtOAC=7:3. |
31 % Chromat. | With N-propyl-1,4-dihydronicotinamide; lithium perchlorate In acetonitrile at 70℃; MeOH, 60 deg C; | |
96 % Chromat. | With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate; silica gel In benzene at 70℃; for 4h; | |
74 %Chromat. | With C29H34BNOP2Ru In dichloromethane; isopropyl alcohol Schlenk technique; Inert atmosphere; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | Stage #1: triphenylmethylphosphonium bromide With potassium-t-butoxide In tetrahydrofuran at 20℃; for 1h; Inert atmosphere; Stage #2: propiophenone In tetrahydrofuran at 20℃; for 1h; Inert atmosphere; | |
64% | Stage #1: triphenylmethylphosphonium bromide With n-butyllithium In tetrahydrofuran at 0℃; for 1h; Inert atmosphere; Stage #2: propiophenone In tetrahydrofuran at 0 - 20℃; Inert atmosphere; | |
59% | Stage #1: triphenylmethylphosphonium bromide With potassium-t-butoxide In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Schlenk technique; Stage #2: propiophenone In tetrahydrofuran at 0 - 20℃; Inert atmosphere; Schlenk technique; |
53% | Stage #1: triphenylmethylphosphonium bromide With n-butyllithium In tetrahydrofuran; hexane at 0℃; for 2h; Stage #2: propiophenone In tetrahydrofuran; hexane at 20℃; for 18h; | |
With sodium hydride; dimethyl sulfoxide 1) 1 h, r.t. 2) overnight, r.t.; Yield given. Multistep reaction; | ||
With n-butyllithium 1.) Et2O, hexane, 4 h, 2.) reflux, overnight; Multistep reaction; | ||
Stage #1: triphenylmethylphosphonium bromide With sodium hydride In tetrahydrofuran for 1h; Reflux; Stage #2: propiophenone In tetrahydrofuran at 0℃; Reflux; | ||
Stage #1: triphenylmethylphosphonium bromide With sodium tertiary butoxide In tetrahydrofuran at 0℃; Inert atmosphere; Schlenk technique; Sealed tube; Stage #2: propiophenone In tetrahydrofuran at 0 - 20℃; for 17h; Inert atmosphere; Schlenk technique; Sealed tube; | ||
Stage #1: triphenylmethylphosphonium bromide With potassium-t-butoxide In tetrahydrofuran at 0℃; for 1h; Inert atmosphere; Stage #2: propiophenone In tetrahydrofuran at 20℃; for 6h; Inert atmosphere; | ||
Stage #1: triphenylmethylphosphonium bromide With potassium-t-butoxide In tetrahydrofuran at 20℃; for 1h; Inert atmosphere; Stage #2: propiophenone In tetrahydrofuran at 20℃; Inert atmosphere; | ||
Stage #1: triphenylmethylphosphonium bromide With potassium-t-butoxide In tetrahydrofuran at 0 - 20℃; for 1h; Inert atmosphere; Stage #2: propiophenone In tetrahydrofuran at 0 - 20℃; Inert atmosphere; | ||
Stage #1: triphenylmethylphosphonium bromide With potassium-t-butoxide In tetrahydrofuran at 0 - 20℃; Stage #2: propiophenone In tetrahydrofuran at 0 - 20℃; | General procedure for the preparation of substituted olefin: General procedure: An oven-dried round-bottom flask was charged with CH3PPh3Br (1.5 equiv.) or CH3CH2PPh3Br (1.5equiv.) and THF (carbonyl substrate concentration = 0.2 M). tBuOK (1.5 equiv.) was added to thesuspension at 0 °C. The resulting mixture was allowed to warm up to room temperature and stirred for 1h. The yellow suspension was cooled to 0 °C again followed by portion-wise addition of the carbonylsubstrate (1 equiv.). Subsequently, the mixture was further stirred at room temperature for 1-12 hours.After the completion of the reaction, the solvent was removed by evaporation, the resulting mixture wasdiluted with water (30 mL) and extract with dichloromethane (3 x 20 mL), and the combined organiclayer was dried with anhydrous Na2SO4. Concentration in vacuo followed by silica gel columnpurification with petroleum ether/ethyl acetate eluent gave the desired product in yields range from 50-95%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With (2-((2,4-dimethyl-5-phenylimidazo[1,5-b]pyridazin-7-yl)amido)-4-methylpentan-1-ol)(1,5-cyclooctadiene)iridium(I); potassium <i>tert</i>-butylate; hydrogen; acetone In tetrahydrofuran at 20℃; for 48h; Autoclave; optical yield given as %ee; enantioselective reaction; | |
98% | With triethylboron hydride; hydrogen; (R)-CoCl2[4'-phenyl-5-OMeCH3PyCH2NH(CH2)2PPh2]; tris(5-ethyl-2-furanyl)phosphine; caesium carbonate In diethyl ether at 25℃; for 12h; Autoclave; enantioselective reaction; | 7. Typical procedures for the asymmetric hydrogenation of ketones General procedure: A glass tube containing a stir bar was charged with the PNN-CoCl2 catalyst 6g (2.8 mg0.005 mmol, 0.02 eq.), Et2O (300 ul), NaBHEt3 (10 ul, 0.01 mmol, 0.04 eq.), thereaction mixture turned to black brown and keep the reaction stirring for 15 min. Toanother glass liner containing a stir bar, ketone (0.25 mmol. 1 eq.), Cs2CO3 (4.1 mg,0.0125 mmol, 0.05 eq.) and phosphine P6 were added step by step. Following this, theactivated catalyst was added with a springe and washed the tube with Et2O (200 ul),and added to the glass liner as well. The glass liner was then placed into an autoclavefollowed by degassing with H2 three times. The hydrogenation was carried out at 40bar H2 with stirring at 25o C for 12 h. After the reaction finished, the hydrogen gas wasthen carefully released in a fume hood, and the solution transferred to a flask toevaporate under vacuum to dryness to obtain the crude product. The crude product waspurified by flash column chromatography (silica gel, PE:EA = 5:1-2:1) to afford the corresponding product. |
97% | With C44H48FeIrNO2P(1+)*C32H12BF24(1-); hydrogen; sodium carbonate In methanol at 20℃; for 24h; Autoclave; enantioselective reaction; |
94% | With ammonium iodide; RhH(CO)(PPh<SUB>3</SUB>)<SUB>3</SUB>; C52H58N4P2; isopropyl alcohol; potassium hydroxide at 65℃; for 4h; enantioselective reaction; | 2.1. Typical procedure for ATH of ketones General procedure: Chiral macrocycles 1 and 2 were synthesized using the same procedure we previously reported [25]. Under air atmosphere, the complex RhH(CO)(PPh3)3 (9.2 mg, 0.01 mmol), (R, R, R', R')-2 (8.0 mg,0.01 mmol), and NH4I (22.0 mg, 0.15 mmol) were placed in a tube equipped with a Teflon-coated magnetic stirring bar. Then, iPrOH was added and the mixture was stirred at 65 °C for 30 min. Next, an appropriate amount of KOH/iPrOH solution was added, and the mixture was continually stirred for another 10 min. Later, ketone was introduced, and the mixture was stirred at the desired temperature for the required reaction time. At the end of experiment, the reaction products were determined by GC using a chiral CP-Chiralsil-Dex CB column. |
93% | With triiron dodecarbonyl; C52H58N4P2; hydrogen; potassium hydroxide In methanol at 45℃; for 10h; enantioselective reaction; | |
93% | With C38H38IrN4S2(1+)*F6P(1-); ammonium formate; 3-methyl-5-p-methoxyphenyl-1-hydropyrazole In tetrahydrofuran; water at 40℃; for 15h; enantioselective reaction; | |
81% | With C22H27Cl2CoN3O; sodium triethylborohydride; 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane In tetrahydrofuran; diethyl ether at 20℃; for 2h; Inert atmosphere; enantioselective reaction; | |
75% | Stage #1: propiophenone With Triethoxysilane; (S,E)-(+)-2,6-diisopropyl-N-(2-((2-(4-phenyl-4,5-dihydrooxazol-2-yl)phenyl)amino)benzylidene)aniline; sodium triethylborohydride; cobalt(II) chloride In tetrahydrofuran; dichloromethane at 20℃; for 15h; Schlenk technique; Inert atmosphere; Stage #2: With potassium carbonate In tetrahydrofuran; methanol; dichloromethane at 20℃; for 2h; Schlenk technique; Inert atmosphere; enantioselective reaction; | |
67% | With bromopentacarbonylmanganese(I); hydrogen; C45H43FeNP2; potassium hydroxide In methanol; toluene at 40℃; for 36h; enantioselective reaction; | |
27% | With trimethoxysilane In tetrahydrofuran for 3h; Ambient temperature; | |
With hydrogenchloride; polymer-supported (S)-(-)-2-amino-3-(p-hydroxyphenyl)-1,1-diphenylpropan-1-ol 1.) THF, 30 deg C; Yield given. Multistep reaction; | ||
With lithium aluminium tetrahydride; (R)-2,2'-dimethoxy-6,6'-dimethylbiphenyl 1) THF, -10 to 20 deg C 2) THF, -100 deg C, 4 h, then -78 deg C, 16 h; Yield given. Multistep reaction; | ||
With borane; (s)-2-amino-1,1-diphenyl-3-(2-naphthyl)-1-propanol In tetrahydrofuran at 30℃; for 3h; Yield given; | ||
Multi-step reaction with 2 steps 1: (1S,2R)-2-amino-1,2-diphenylethanol; benzoic acid / hexane / 12 h / 20 °C | ||
Multi-step reaction with 2 steps 1: NaBH4 / methanol 2: lipase B (Candida antarctica, Novozym 435); molecular sieves 4 Angstroem; Et3N / toluene / 163 h / 30 °C / Enzymatic reaction | ||
With recombinant stereospecific carbonyl reductase 1 from Candida parapsilosis; NAD In aq. phosphate buffer at 30℃; for 6h; | ||
With D-glucose; lyophilized cells of Escherichia coli pET28a-CpAR2-BmGDH; potassium carbonate In ethanol at 30℃; Green chemistry; enantioselective reaction; | ||
>99 % ee | With Debaryomyceshansenii carbonyl reductase N179S/I214F/S215G; NADPH In aq. phosphate buffer at 30℃; for 2h; Enzymatic reaction; stereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With bis(1,5-cyclooctadiene)diiridium(I) dichloride; C53H73FeN2O2PS; hydrogen; lithium tert-butoxide In isopropyl alcohol at 25 - 30℃; for 12h; Autoclave; enantioselective reaction; | |
99% | With bis(1,5-cyclooctadiene)diiridium(I) dichloride; hydrogen; C41H44N3O3P; barium(II) hydroxide In ethanol at 40℃; for 1h; Autoclave; enantioselective reaction; | |
96% | With sodium tetrahydroborate; third-generation glucose-persubstituted amidoamine dendrimer In tetrahydrofuran at 25℃; |
96% | With C58H56Cl2N2P2Ru; potassium <i>tert</i>-butylate; hydrogen In isopropyl alcohol at 25℃; for 3h; Inert atmosphere; optical yield given as %ee; | |
96% | With potassium <i>tert</i>-butylate; hydrogen In isopropyl alcohol at 20℃; for 24h; Autoclave; optical yield given as %ee; enantioselective reaction; | |
96% | With D-glucose In aq. phosphate buffer at 28℃; for 4h; Microbiological reaction; enantioselective reaction; | Typical procedure for the preparation of the biocatalysts and for biotransformations: General procedure: Pichia glucozyma CBS 5766 was cultured using malt extract +0.5% yeast extractmedium (malt broth, yeast extract 5 g/L, pH 6.0) in a 3.0 L fermenter with 1.0 Lof liquid medium for 24 h, at 28 C and agitation speed 100 rpm. Cells fromsubmerged cultures were harvested by centrifugation and washed with 0.1 Mphosphate buffer, pH 7.0. Reductions were carried out in 100 mL screw-cappedtest tubes with a reaction volume of 50 mL with cells (2.5 g, dry weight)suspended in 0.1 M phosphate buffer, pH 7.0 containing 50 g/L of glucose. After30 min of incubation, substrates (20 mM) were added and the incubationcontinued for 24 h under magnetic stirring. When the reaction was over, pH wasbrought to pH 1 by the addition of 1 M HCl and 35 mL of EtOAc was added andthe resulting mixture was shaken and centrifuged; the aqueous phase wasextracted twice more with 35 ml of EtOAc. The organic phases were collectedand dried over Na2SO4 and the solvent was evaporated. The crude residues werepurified by flash chromatography. |
96% | With dichloro(benzene)ruthenium(II) dimer; potassium <i>tert</i>-butylate; hydrogen; (R)-N,N'-((1R,2R)-cyclohexane-1,2-diyl)bis(2-((R)-tert-butyl(methyl)phosphino)benzamide) In isopropyl alcohol at 20℃; for 8h; Schlenk technique; enantioselective reaction; | 3.General procedu re for asymmetric hydrogenation General procedure: The [Ru(C6H6)Cl2]2(1.5 mg, 3 10-3 mmol, 1.0 mol%), (Rc,Rc,Rp,Rp)-L1 (3.5 mg, 6.610-3 mmol, 1.1 mol%) and isopropanol (1.5 mL) were added to a schlenk tube under an atmosphere of argon. After stirring at room temperature for 1.0 h, the orange-yellow solution was transferred to a stainless-steel reactor via syringe in a glovebox. Next, tBuOK (6.7 mg, 0.060 mmol, 10.0 mol%), and acetophenone (72.0 mg, 0.60 mmol, 1.0 eq) were added into the solution, and the resulting mixture was stirred under a hydrogen pressure (3.0 MPa) at room temperature for 8.0 h. The pure products were obtained by flash column chromatographic purification using petroleum and ethyl acetate as the eluent. The pure products were obtained by flash column chromatography using petroleum and ethyl acetate as the eluent. The enantiomeric excesses were measured by chiral HPLC using the Daicel chiral OD-H (4.6 mm × 250 mm, 5 μm) and REGIS (R,R)-WHELK-O1 (2.1 mm × 150 mm, 5 μm) columns and 2-propanol/hexane as the eluent. The absolute configurations of the corresponding products were determined by comparison of the results with literature reports. |
95% | Stage #1: propiophenone With diethoxymethylane; C36H31FeN3O3 In toluene at -78 - 20℃; for 6h; Schlenk technique; Inert atmosphere; Stage #2: With potassium carbonate In methanol at 20℃; for 1h; Schlenk technique; Inert atmosphere; enantioselective reaction; | |
93% | With bis(1,5-cyclooctadiene)diiridium(I) dichloride; C37H35FeN2P; hydrogen; potassium carbonate In methanol at 20℃; for 12h; Glovebox; Autoclave; enantioselective reaction; | General procedure for asymmetric hydrogenation of ketones General procedure: In a nitrogen-filled glovebox, a stainless steel autoclave was charged with [Ir(COD)Cl]2(3.4 mg, 0.005 mmol) andL2(6.6 mg, 0.11 mmol) in 1.0 mL of dry MeOH. After stirring for 1h at room temperature, a solution of the substrates1(1.0 mmol) andK2CO3(6.9 mg, 0.05 mmol) in 2.0 mL of MeOH was added to the reaction mixture, and then the hydrogenation was performed at room temperature under an H2pressure of 20 bar for 12 h. The solvent was then evaporated and the residue was purified by flash column chromatography to give the corresponding hydrogenation product which was analyzed by chiral HPLC to determine the enantiomeric excesses. |
90% | With sodium tetrahydroborate; G(3)G amphiphilic dendrimer In tetrahydrofuran for 12h; Ambient temperature; | |
90% | With sodium tetrahydroborate; D-gluconamide PAMAM dendrimer G(3)G In tetrahydrofuran at 25℃; | |
88.3% | With borane-THF; (R)-2-amino-3-(1-naphthyl)-1,1-diphenyl-1-propanol In tetrahydrofuran at 30℃; | |
86% | Stage #1: propiophenone With 1-((1R,2R)-2-(benzylamino)cyclohexyl)-3-(3,5-bis(trifluoromethyl)phenyl)thiourea; benzo[1,3,2]dioxaborole In toluene at -46℃; for 24h; Molecular sieve; Inert atmosphere; Stage #2: With methanol; sodium hydroxide In toluene at -46 - 20℃; optical yield given as %ee; enantioselective reaction; | |
80% | Stage #1: propiophenone With [Ir(COD)2]BF4; diethoxymethylane; C26H30N3O2(1+)*Cl(1-) In tetrahydrofuran at 20℃; for 20h; Inert atmosphere; Stage #2: With potassium carbonate In tetrahydrofuran; methanol at 20℃; for 2h; enantioselective reaction; | 4.3. General procedure for asymmetric hydrosilane reduction General procedure: To a THF (2 mL) solution of [Ir(cod)2]BF4 (0.02 mmol, 9.9 mg) and azolium salt 1 (0.02 mmol, 9.1 mg) were added propiophenone (4, 0.50 mmol, 67 mg), (EtO)2MeSiH (2.25 mmol, 302 mg). After stirring at room temperature for 20 h under open-air conditions, K2CO3 (2 mg) and MeOH (2 mL) were added. Then, the resulting mixture was stirred at room temperature for 2 h. After evaporation of the solvents, the residue obtained was purified by column chromatography on silica gel (Et2O/n-hexane = 3:7) to give (S)-1-phenyl-1-propanol ((S)-5, 62 mg, 91% isolated yield). The ee was measured by chiral GLC. |
79% | With [2-(4,4'-trifluoromethylbenzhydryl)-5-(2,4,6-trihexylphenyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-2-ylidene](1,5-cyclooctadiene)iridium chloride; potassium <i>tert</i>-butylate In isopropyl alcohol at 70℃; for 1h; Inert atmosphere; enantioselective reaction; | |
78% | With diisopinocamphenylchloroborane In tetrahydrofuran at -25℃; for 7h; | |
72% | Stage #1: propiophenone With silver tetrafluoroborate; diethoxymethylane; C30H39ClIrN3O2 In tetrahydrofuran at 20℃; for 15h; Stage #2: With potassium carbonate In tetrahydrofuran; methanol at 20℃; for 2h; enantioselective reaction; | |
72% | With C30H32ClN2O2RuS; hydrogen; potassium hydroxide In 2,2,2-trifluoroethanol at 40℃; for 24h; Autoclave; enantioselective reaction; | |
70% | With potassium hydroxide; 9-amino-9-deoxyepicinchonine In isopropyl alcohol at -20℃; for 24h; | |
56% | With D-glucose; Bacillus megaterium glucose dehydrogenase; Pichia glucozyma CBS 5766 recombinant NADPH-dependent benzil reductase; NADPH In dimethyl sulfoxide at 25℃; for 24h; Enzymatic reaction; enantioselective reaction; | |
29% | With Aspergillus niveus 12276 In various solvent(s) | |
With 2,2'-iminobis[ethanol]; (-)-diisopinocamphenylborane chloride 1) THF, -25 deg C, 5 h; 2) ethyl ether, 2 h; Yield given. Multistep reaction; | ||
291 mg | With (-)-(S)-BINAL-H In tetrahydrofuran 1.) -100 deg C, 3 h; 2.) -78 deg C, 16 h; | |
27 % Chromat. | In water at 30℃; for 3h; Geotrichum candidum IFO4597 on a diluted medium (glycerol, yeast extract, polypeptone); | |
With Tetrahydrofurfuryl alcohol; sodium tetrahydroborate In ethanol; chloroform at 0℃; for 0.5h; Yield given; | ||
With phosphate buffer; Pichia minuta CBS 1708 for 24h; | ||
Cryptococcus macerans; | ||
Multi-step reaction with 2 steps 1: (1S,2R)-2-amino-1,2-diphenylethanol; benzoic acid / hexane / 12 h / 20 °C | ||
Multi-step reaction with 2 steps 1: NaBH4 / methanol 2: lipase B (Candida antarctica, Novozym 435); molecular sieves 4 Angstroem; Et3N / toluene / 163 h / 30 °C / Enzymatic reaction | ||
With glucose dehydrogenase; D-glucose In various solvent(s) at 30℃; for 24h; | ||
90 % ee | With alcohol dehydrogenase from ralstonia sp; NADP; isopropyl alcohol In aq. phosphate buffer at 30℃; for 24h; Green chemistry; Enzymatic reaction; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate; acetic acid for 1.3h; Irradiation; Inert atmosphere; | Reduction of α-Haloketones 2; General Procedure General procedure: Into a flask charged with the respective α-haloketone 2 (1 mmol) and ethidine (Hantzsch's ester, 1a; 1.2 mmol), was added the solvent as per Tables 2-4 (2.5 mL). The flask was then attached to a balloon filled with N2 and irradiated with 3 W blue LED at a distance of 5 cm. The workup was followed when TLC showed that ethidine or the haloketone was consumed. When AcOH was used as the solvent, the reaction was worked up as follows: the reaction mixture was partitioned between EtOAc (40 mL) and H2O (10 mL), then the organic phase was washed with sat. aq NaHCO3 (3 15 mL) and brine (15 mL), and dried (anhyd Na2SO4). After concentration under reduced pressure, the residue was subjected to flash chromatography for purification eluting with petroleum ether (PE) and CH2Cl2. When aprotic polar solvents were used, the reaction mixture was diluted with EtOAc (40 mL) and the organic layer was washed with H2O (3 15 mL) and brine (15 mL), and dried (anhyd Na2SO4). When volatile solvents were used, the mixture was concentrated under reduced pressure and the residue was subjected to flash chromatography for purification. |
90% | With N,N,N,N,-tetramethylethylenediamine; diisobutylaluminium hydride; tin(ll) chloride In tetrahydrofuran; toluene at -78℃; for 0.166667h; | |
85% | With indium; water for 7.5h; ultrasound; |
With hydrogen selenide; triethylamine In methanol at -20℃; for 3h; Yield given; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With toluene-4-sulfonic acid In methanol at 25℃; for 18h; Inert atmosphere; | |
96% | With Pd(PhCN)<SUB>2</SUB>(OTf)<SUB>2</SUB> In methanol at 20℃; Inert atmosphere; | 4-Bromobenzaldehyde Dimethyl Acetal (1); Typical Procedure General procedure: An oven-dried, argon-flushed, 10 mL round-bottomed flask wascharged with 4-bromobenzaldehyde (92.5 mg, 0.5 mmol, 1.0equiv) and HC(OMe)3 (0.16 mL, 1.5 mmol, 3.0 equiv). To thismixture was added a preformed solution of Pd(PhCN)2(OTf)2(0.2 mL, 0.0025 mmol, 0.5 mol%), generated in situ fromPd(PhCN)2Cl2 (0.96 mg, 0.0025 mmol, 0.5 mol%) and AgOTf(1.29 mg, 0.005 mmol, 1 mol%) in anhyd CH2Cl2 (0.2 mL). The resulting mixture was stirred at r.t. until the reaction was complete(TLC) then directly purified by flash column chromatography[silica gel, hexanes-EtOAc (4:1) + Et3N (1%)] to give a colorlessoil; yield: 112 mg (97%). |
88% | With toluene-4-sulfonic acid In methanol at 20℃; |
In methanol | ||
With toluene-4-sulfonic acid In methanol at 0℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
(i) HCO2NH4, (heating), (ii) aq. HCl; Multistep reaction; | ||
With ammonium acetate; sodium cyanoborohydride In methanol | ||
Multi-step reaction with 2 steps 1: 3 h / 165 °C 2: 6N aq. HCl / 16 h / Heating |
Multi-step reaction with 2 steps 1: formic acid 2: aqueous HCl | ||
With ammonia In ethanol Inert atmosphere; | ||
With ammonium acetate; sodium cyanoborohydride In methanol at 20℃; for 12h; | General procedure: 1-(2-methylphenyl)ethanone (0.50 mL, 3.73 mmol) and ammonium acetate (2.88 g, 37.3 mmol) were dissolved in methanol (20 mL). To the stirred solution was added slowly a solution of NaCNBH3 (0.79 g, 11.2 mmol) dissolved in methanol (15 mL) through a dropping funnel. The whole mixture was stirred at room temperature. After stirring for 12 h, solvent was removed by using rotary evaporator. The residue was dissolved in ethyl acetate and then the solution was treated with 6 N HCl solution to makethe solution to be acidic (pH = 12-13). The two layers were separated and then 6 N NaOH solutionwas added to the separated aqueous solution to make the solution to be basic (pH = 11-12). The basic aqueous solution was extracted with ethyl acetate twice and then combined organic solution was dried over anhydrous Na2SO4. Solvent was removed by using rotary evaporator to afford an intermediateamine B, 1-(2-methylphenyl)ethylamine (Ar = 2-methylphenyl, R1 = CH3, compound B in Figure 5) (0.21 g, 46% yield). | |
With ammonia In ethanol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With hydrogenchloride; tert.-butylnitrite In tetrahydrofuran; 1,4-dioxane at 20℃; for 3h; | C 1-Phenyl-butane-1,2-dione 2-oxime: To a stirred solution of the butyrophenone (300 mg, 2.0 mmol) in tetrahydrofuran (8 mL) was added t-butyl nitrite (0.475 mL, 4.0 mmol) and hydrochloric acid (4N in dioxane, 0.65 mL, 2.6 mmol). The reaction was stirred at RT for 3 hours, then the solvent was evaporated and the residue was purified by Prep HPLC (ammonium acetate/water/acetonitrile) to give the title material (0.200 g, 56%). HPLC 91% (220 nm), LCMS (+ESI, M+H+) m/z 178; 1H NMR (400 MHz, methanol-d4) δ (ppm): 1.13 (3H, t, J=7.6 Hz), 2.71 (2H, qa, J=7.6 Hz), 7.45 (2H, br t), 7.57 (1H, br t), 7.90 (2H, d, J=7.0 Hz). |
With n-Amyl nitrite; sodium ethanolate 1.) EtOH, 2.) EtOH, 2 h; Multistep reaction; | ||
With chloro-trimethyl-silane; isopentyl nitrite In dichloromethane at -20 - 20℃; for 1h; | 2.2 Synthesis of the Acyl Radical Precursors General procedure: The above oxime esters 2a-2e, 2g-2s were synthesized according to the method below.[1]Step 1: To a solution of 10 mmol ketone in 5 mL DCM was added 1 eq. TMSCl ( trimethylchlorosilane, 1.24 mL)at -20 . To this cooled solution was dropwise added 1 eq. isoamyl nitrite (1.34 mL). The reaction was found to beinstantaneous, but the mixture was stirred at r.t. for an additional period of 1 h before working up. The solution wasdirectly concentrated in vacuo. The crude product was purified by flash column chromatography on silica gel (elutingwith hexane/ethyl acetate = 20:1) and the corresponding oximes I was obtained.Step 2: To a solution of 10 mmol oxime I and 1.5 eq. triethylamine (2.08 mL) in 20 mL DCM was slowly added asolution of 1.2 eq. acyl chloride in DCM (5 mL) at 0 . The mixture was stirred at r.t. for 2 h. After completion, thereaction was quenched with 50 mL NaHCO3 saturated solution and extracted with 50 mL DCE for three times. Theextract was washed with brine and dried over Na2SO4 and concentrated in vacuo. The crude product was purified by flashcolumn chromatography on silica gel (eluting with hexane/ethyl acetate = 20:1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | Stage #1: propiophenone With lithium diisopropyl amide In tetrahydrofuran; hexane at -40℃; for 1h; Stage #2: With indium(III) chloride In tetrahydrofuran; hexane at -40 - 25℃; for 1.5h; Stage #3: benzaldehyde In tetrahydrofuran; hexane at 25℃; for 2h; stereoselective reaction; | General procedure for the synthesis of racemic (l,l,l,u)-tetrahydro-2H-pyrans General procedure: A solution of diisopropylamine (1.26 mL, 9.00 mmol) in THF (30 mL) was treated with 3.00 mL of n-butyllithium (2.5 M in n-hexane, 7.50 mmol) at 0 °C and stirred for 15 min. After cooling down to -40 °C, pro-piophenone (1a) (1.01 mL, 7.50 mmol) was added and the mixture was stirred at -40 °C for 1 h. Then 2.5 mmol of the metal halide were added. The yellow reaction mixture was stirred for 30 min at -40 °C and for 1 h at room temperature. After that it was treated with a solution of benzaldehyde (3a) (250 mg, 2.50 mmol) in 30 mL of THF at different reaction temperatures and the reaction mixture was stirred for 2 h at the corresponding reaction temperatures (see Tables in manuscript). It was quenched with saturated aqueous ammonium chloride solution (50 mL) and the aqueous layer was extracted three times with diethyl ether (30 mL). The combined organic layers were washed with brine and dried over Na2SO4. In case of the following metals the general procedure was modified: a) Ti(OiPr)2Cl2: 700 L of diisopropylamine (5.50 mmol), 2.00 mL of n-BuLi (2.5 M in n-hexane, 5.50 mmol) and 660 L of propiophenone (1a) (5.50 mmol) in THF (30 mL) were used. The addition of the aldehyde solution was done at reflux temperature. b) ZrCl4: The neat aldehyde was added. The overall amount of THF was 30 mL. c) SnCl4: 720 L of diisopropylamine (5.10 mmol), 2.00 mL of n-BuLi (2.5 M in n-hexane, 5.00 mmol) and 660 L of propiophenone (5.00 mmol) were reacted. |
40% | With titanium(IV) dichlorodiisopropylate; lithium diisopropyl amide In tetrahydrofuran at 67℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With caesium carbonate In 1,4-dioxane for 8h; Reflux; | |
59% | With C20H19Cl2PPdS; caesium carbonate In 1,4-dioxane; dichloromethane at 100℃; for 16h; | 2.7 Catalytic activity of 1a and 1b in acylation reaction General procedure: Aryl halides (2mmol) and aldehydes (2.4mmol) in 1, 4 - dioxane (20cm3) were mixed together. The base cesium carbonate (6mmol) and the respective catalyst (0.004mmol) in dichloromethane (5cm3) were then added to the solution and stirred at 100°C. The reactions were monitored by TLC and the products were isolated by silica gel column chromatography using ethyl acetate and hexane as eluents. The products were characterized by 1H NMR, 13C NMR and melting point determination followed by their comparison with the standard literature data. |
33% | With dibromo[1,2-bis(diphenylphosphino)ethane]nickel(II); zinc In tetrahydrofuran at 110℃; for 36h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium isopropylate; acetone In isopropyl alcohol at 50℃; for 0.5h; | ||
Stage #1: 1-Phenyl-1-butanol With Mn<SUP>III</SUP>(L-5-t-Bu)(Cl); 1-butyl-2,6-dimethyl-pyridinium; bromide In dichloromethane; water at 20℃; Stage #2: With [bis(acetoxy)iodo]benzene In dichloromethane; water at 20℃; for 0.1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: n-propylmagnesium bromide With zirconocene dichloride Stage #2: propiophenone In benzene at 0℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
10% | With sodium hypochlorite; tetra(n-butyl)ammonium hydrogensulfate In dichloromethane at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With benzophenone; potassium <i>tert</i>-butylate In 1,4-dioxane at 90℃; for 0.5h; Inert atmosphere; | |
87% | With potassium hydroxide; 1,3-diisopropyl-1H-benzo[d]imidazol-3-ium bromide In toluene at 60℃; for 1h; | |
85% | With [(η5-C5Me5)Ir(6,6'-dihydroxy-2,2'-bipyridine)(H2O)]OTf2; potassium hydroxide In water at 100℃; for 12h; |
85% | With [(η5-C5Me5)Ir(6,6'-dihydroxy-2,2'-bipyridine)(H2O)]OTf2; potassium hydroxide In water for 12h; Reflux; Green chemistry; | 18 3-ethyl-2-phenylquinoline Butyrophenone (178 mg, 1.2 mmol),[Cp * Ir (6,6 '- (OH) 2bpy) (H2O)] [OTf] 2 (8.3 mg,0.01 mmol, 1 mol%), potassium hydroxide (56 mg, 1.0 mmol, 1.0 equiv.), O-aminobenzyl alcohol (123 mg, 1.0 mmol) and water (1 mL) were sequentially added to a 5 mL round bottom flask.The reaction mixture was refluxed in air for 12 hours and then cooled to room temperature.It was extracted with ethyl acetate, the solvent was removed by rotary evaporation and the pure target compound was obtained by column chromatography (developing solvent: petroleum ether / ethyl acetate). Yield: 85% |
82% | With [(p-cymene)Ru(BiBzImH2)Cl][Cl]; caesium carbonate In tert-Amyl alcohol at 125℃; for 12h; | 4.4. Procedure for acceptorless dehydrogenative coupling of ketoneswith o-aminobenzyl alcohols to quinolines catalyzed by [(p-cymene)Ru(BiBzImH2)Cl][Cl] General procedure: In a round-bottomed flask with a condenser tube were added oaminobenzylalcohols 1 (1 mmol) and ketones 2 (1.2 mmol, 1.2equiv), cat. 1 (6 mg, 0.01 mmol, 1 mol %), Cs2CO3 (163 mg,0.5 mmol, 0.5 equiv) and tert-amyl alcohol (1 mL). The reactionmixture was heated at 125 C in an oil bath for 12 h and thencooled to ambient temperature, concentrated in vacuo and purifiedby flash column chromatography with hexane/ethyl acetate (10:1,v/v) to afford corresponding products. |
78% | With benzophenone; potassium <i>tert</i>-butylate In 1,4-dioxane at 90℃; for 0.5h; Inert atmosphere; | |
78% | With trifuran-2-yl-phosphane; C48H34F6N4O4Pd2; lithium hydroxide In neat (no solvent) at 100℃; for 24h; Inert atmosphere; Schlenk technique; Sealed tube; | |
76% | With potassium <i>tert</i>-butylate In 1,4-dioxane at 90℃; Inert atmosphere; | |
67% | With potassium hydroxide; benzophenone In 1,4-dioxane at 80℃; | |
67% | With potassium hydroxide; benzophenone In 1,4-dioxane at 80℃; for 24h; | |
65% | With (6,8,15,17-tetramethyl-7H,16H-5,9,14,18-tetraaza-dibenzo[b,i]-cyclotetradecenato(2-)-k(4)-N,N',N'',N''')nickel(II); potassium <i>tert</i>-butylate In toluene at 90℃; Inert atmosphere; Schlenk technique; Sealed tube; Green chemistry; | |
58% | With dimethyl sulfoxide; potassium hydroxide at 80℃; for 7h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With tert.-butylhydroperoxide; iodine In decane; dimethyl sulfoxide at 80℃; for 6h; | |
69% | With iodine; dimethyl sulfoxide at 60℃; for 24h; | |
65% | With iodine; dimethyl sulfoxide at 60℃; for 24h; Schlenk technique; | 10 Example 102 - hydroxy -1 - phenyl butanone Taking a 25 ml Schlenk reaction tube, iodize elemental (I2) 26 mg (0.1mmol) as catalyst, 1 - phenyl butanone 75 mg (0.5mmol), dimethyl sulfoxide (DMSO) 0.5 ml as the oxidizing agent, carbonylating and solvent, for 60 °C stirring for 24 hours. After the reaction by adding ethyl acetate 15 ml, salt water 3 ml, ethyl acetate 3 times, the combined organic phase, column chromatography separation to obtain 2 - hydroxy -1 - phenyl butanone pure product 56 mg, yield 65%. |
58% | With 1,4-diaza-bicyclo[2.2.2]octane; iodine In methanol at 20℃; for 27h; Irradiation; | 13 Example 13 A green preparation method of α-hydroxy ketone, the method is to sequentially add 0.3 mmol of 1-phenyl-1-butanone,Iodine 0.06 mmol, 1,4-diazabicyclo[2.2.2] octane 0.15 mmol (DABCO),Add 2.0 mL of methanol to a 5 mL glass reaction flask; then under the irradiation of a 23 W compact fluorescent lamp (CFL), the reaction was stirred at room temperature in an air atmosphere for 27 h to obtain a reaction mixture, which was separated by silica gel column chromatography.1-Phenyl-2-hydroxy-1-butanone 28.6 mg, its structural formula is as follows:Among them: the mobile phase used for silica gel column chromatography is a mixture obtained by mixing PE and EtOAc at 15 mL:1 mL.The analytical results of the obtained product 1-phenyl-2-hydroxybutan-1-one are as follows: pale yellow liquid, yield 58%. |
48% | With iodine; dimethyl sulfoxide; copper(II) oxide at 65℃; for 12h; | |
Multi-step reaction with 3 steps 1.1: LDA / tetrahydrofuran / 1 h / -78 °C 1.2: 90 percent / tetrahydrofuran / -78 - 20 °C 2.1: 85 percent / m-chloroperbenzoic acid / CH2Cl2 / -20 °C 3.1: 76 percent / trifluoroacetic acid / diethyl ether; H2O / 5 °C | ||
Multi-step reaction with 2 steps 1: diethyl ether; PBr5 / 40 - 50 °C 2: methanol; potassium formate | ||
With iodine; dimethyl sulfoxide at 60℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With trifluorormethanesulfonic acid; palladium diacetate; 2-(3,5-dimethyl-1H-pyrazol-1-yl)pyridine In water at 60℃; for 4.5h; | General procedure for addition of arylboronic acids to nitrile General procedure: To a mixture of arylboronic acid (1.2 mmol), nitrile (1.0 mmol), Pd(OAc)2 (4 mol%)and L1 (4 mol%), H2O (1.2 mL) and triflic acid (0.4 mL) were added and stirred at 60 °Cunder air for desired time (TLC monitoring). Then the reaction mixture was neutralized withsaturated NaHCO3 solution and extracted with ether. The combined ether solution waswashed with brine, dried by Na2SO4 and concentrated. The residue was purified by flashcolumn chromatography on silica gel using petroleum ether/cetone or petroleum ether/DCMas eluent to give the desired product. |
83% | With 1,10-Phenanthroline; nickel(II) bromide diethylene glycol dimethyl ether; sodium hydrogencarbonate In water at 100℃; for 5h; Autoclave; | General procedure for the synthesis of arylketones 3a-y: General procedure: The reaction was carried out in an autoclave containing a 10 mL Teflon reactiontube. NiBr2·diglyme (5 mol%), 1,10-phen (10 mol%) and a magnetic stir bar wereplaced in the tube. Then, arylboronic acid (1.0 mmol), NaHCO3 (2.0 equiv), H2O (2.0mmol) and alkyl nitrile (1.0 mL) were added to the tube. After that the autoclave wascapped with a stopper. The autoclave was cool down by liquid nitrogen, then createdvacuum at this temperature and added HCFC-244bb (2.0 mL, 2.6 g) by self-suction.Finally the autoclave was wormed in an oil bath at 100 °C for 5 h. After the reaction,the autoclave was cooled to room temperature and vented the excess HCFC-244bb carefully. Water (30 mL) was added to the mixture, and the mixture was extractedwith dichloromethane (3 x 15 mL). The organic layers were washed with brine, driedover Na2SO4, and evaporated the organic solvent by rotatory evaporator. The crudeproduct was then purified by column chromatography. |
76% | With bathophenanthroline; water; copper diacetate; manganese(III) triacetate dihydrate In 1,4-dioxane at 90℃; | General procedure for the synthesis of arylketones General procedure: In a 25mL round bottom flask (oven-dried overnight) was added the phenyl boronic acid (1a, 1.0 mmol) followed by the addition of 1,4-dioxane (6mL). To this solution, manganese (III) acetate. dihydrate (5mol%), Bphen (3e, 10mol%), Cu(OAc)2 (5mol%), nitrile (0.5mmol) and water (0.5mmol) were added sequentially. The reaction was then stirred at room temperature for 10min and slowly brought to 90°C under air. The reaction was allowed to run for overnight at the same temperature. After the completion, the reaction mixture was quenched and extracted with ethyl acetate and water. The organic layer was collected, and the aqueous layer was again extracted with ethyl acetate for three more times. The combined organic layer was further washed with sodium bicarbonate and brine solution. The organic layer was then dried over sodium sulfate, filtered and evaporated using rotavap. The crude compound obtained was further purified using column chromatography (EA:hexane 10:90). |
69% | With 1,2-bis(diphenylphosphino)ethane nickel(II) chloride; water; zinc(II) chloride In 1,4-dioxane at 80℃; for 8h; Inert atmosphere; | |
59% | In nitromethane for 24h; Heating; | |
38% | With ammonium chloride In water at 100℃; for 24h; | |
31% | With [2,2]bipyridinyl; potassium fluoride; acetic acid In tetrahydrofuran at 80℃; for 48h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium hydroxide; acetone; N,N'-bis[o-(diphenylphosphino)benzylidene]-(1S,2S)-diaiminocyclohexane In isopropyl alcohol at 25℃; for 8h; | ||
With bis(1,5-cyclooctadiene)diiridium(I) dichloride; bis(triphenylphosphine)iminium chloride; acetone; potassium hydroxide; N,N'-bis[o-(diphenylphosphino)benzylidene]-(1S,2S)-diaiminocyclohexane In dichloromethane; water; isopropyl alcohol at 28℃; for 24h; Resolution of racemate; Inert atmosphere; optical yield given as %ee; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With C30H29BrMnNO2P2; potassium <i>tert</i>-butylate In toluene at 120℃; for 1h; | |
92% | With chloro(1,5-cyclooctadiene)rhodium(I) dimer; potassium hydrogen difluoride; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In methanol; toluene at 70℃; for 15h; Inert atmosphere; Glovebox; Sealed tube; | |
88% | With Fe(II)(bis(2-(diisopropylphosphino)ethyl)amine)(CO)(H)(Cl); potassium <i>tert</i>-butylate In toluene at 80℃; for 1h; Inert atmosphere; |
88% | With chloro(1,5-cyclooctadiene)rhodium(I) dimer; cesium acetate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In tetrahydrofuran at 70℃; for 15h; Glovebox; Sealed tube; Inert atmosphere; | |
With (R,R)-1,2-diphenylethylenediamine; potassium <i>tert</i>-butylate; cyclohexanone In tetrahydrofuran at 60℃; for 20h; | ||
100 %Chromat. | With carbonyl bis(hydrido)tris(triphenylphosphine)ruthenium(II) In 1,3,5-trimethyl-benzene at 165℃; for 24h; Inert atmosphere; | |
With palladium (II) acetate; bis(pinacol)diborane; tricyclohexylphosphine In toluene at 80℃; for 12h; Sealed tube; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 63 % Spectr. 2: 19 % Spectr. 3: 9 % Spectr. | With triethylamine In toluene at 200℃; for 12h; | |
1: 30 % Spectr. 2: 19 % Spectr. 3: 9 % Spectr. | With triethylamine In toluene at 150℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | Stage #1: propiophenone With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78℃; for 1.5h; Stage #2: With N-fluorobis(benzenesulfon)imide In tetrahydrofuran; hexane at -78 - 20℃; for 12h; | |
70% | With triethylamine pentahydrogen fluoride salt; 1-iodosyl-4-methylbenzene In 1,2-dichloro-ethane at 60℃; for 24h; Sealed tube; | |
Multi-step reaction with 3 steps 1: titanium(IV) chloride / diethyl ether; pentane / 15 h / 0 - 20 °C 2: 71 percent / N-fluorobenzenesulfonimide; potassium carbonate / acetonitrile; dimethylformamide / 0 °C 3: 90 percent / aq. HCl / CH2Cl2 / 2 h / 20 °C |
Multi-step reaction with 2 steps 1: Br2 / CCl4 / 0.5 h / Ambient temperature 2: KF / dimethylformamide / 3 h / Heating | ||
Stage #1: propiophenone With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78℃; for 1.5h; Inert atmosphere; Stage #2: With N-fluorobis(benzenesulfon)imide In tetrahydrofuran; hexane at -78 - 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: cumene hydroperoxide / 20 h / 120 °C 2: cumene hydroperoxide / o-xylene / 35 h / 120 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With hydroxylamine hydrochloride; sodium acetate In ethanol; water Reflux; | General Procedure A1: Synthesis and Characterization of Oximes General procedure: To a 100 mL round bottom flask charged with a stir bar, sodium acetate (1.64 g, 20.0mmol,) and hydroxylamine hydrochloride (1.04 g, 15.0 mmol), was added a solution ofthe ketone (0.3 M) in ethanol/water (4:1). The reaction mixture was then heated toreflux until all the ketone starting material was consumed as indicated by TLC. After reflux, the reaction was allowed to cool to room temperature. The crude mixture wasobtained after removal of excess ethanol. To the crude mixture was added 20 mL ofwater. The resulting aqueous solution was extracted with ethyl acetate (20 mL × 3).The combined organic layers were then washed with water (20 mL × 2) and brine (20mL × 1), dried over anhydrous MgSO4, filtered and concentrated. The oxime productwas used directly in the next step. In certain cases, the oxime product was obtained afterflash column chromatography or recrystallization using the indicated solvent mixture. |
With hydroxylamine hydrochloride; sodium acetate In ethanol; water for 20h; Reflux; | ||
With lithium hydroxide monohydrate; hydroxylamine hydrochloride In water at 70℃; for 8h; Schlenk technique; Sealed tube; Green chemistry; | 4.1 General procedure for the synthesis of the products General procedure: Benzaldehyde 1a (98%, 21.6mg, 0.2mmol), hydroxylamine hydrochloride 2 (98%, 18.4mg, 0.26mmol), and lithium hydroxide monohydrate (90%, 37.3mg, 0.8mmol) were weighed to a sealed Schlenk flask (25mL), and water (0.3mL) was added via syringe at room temperature. After that the Schlenk flask was immersed in an oil bath at 70°C and stirred until the total conversion of benzaldehyde (by TLC). And then pentafluorobenzonitrile 3 (98%, 59.1mg, 0.3mmol) was added to the mixture and the reaction system was stirred at 70°C until it was completed. Water (5mL) was added to the Schlenk flask and extracted with ethyl acetate (3×10mL). The organic extracts were combined, dried with anhydrous magnesium sulfate and then concentrated in vacuo. The residue was purified on silica gel to afford the product 4a (44.7mg, 76% yield). |
With hydroxylamine hydrochloride; sodium acetate In ethanol; water at 95℃; | ||
With hydroxylamine hydrochloride; sodium acetate In ethanol Inert atmosphere; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium tetrahydroborate In methanol at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 3-chloro-benzenecarboperoxoic acid; (S)-1-ethyl-2-iodo-3-(1-methoxyethyl)benzene at 20℃; optical yield given as %ee; enantioselective reaction; | ||
48 % ee | With (4S,5S)-2-(5-chloro-2-iodo-3-methylphenyl)-4-methyl-5-phenyl-4,5-dihydrooxazole; 3-chloro-benzenecarboperoxoic acid In dichloromethane; acetonitrile at 20℃; for 25h; Overall yield = 70 %; enantioselective reaction; | |
46 % ee | With (aS)-2,8-diiodo-5-(1,1':3',1''-terphenyl-2'-yl)-10,11,12,13,14,15,16,17-octahydro-4H-dinaphtho[1',2':7,8;2'',1'':5,6][1,4]dioxocino[2,3-c]pyrrole-4,6(5H)-dione; 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 60h; Inert atmosphere; Overall yield = 29 %Spectr.; enantioselective reaction; | α-Oxytosylation of Ketones; General Procedure General procedure: The appropriate catalyst (10 mol%; 0.01 M), PTSA (13 mg, 0.075 mmol), and m-CPBA (13 mg, 0.075 mmol)23 were added to a sealed flask and purged with argon. A 0.1 M solution of substrate 6 in CH2Cl2 (0.5 mL, 0.05 mmol) was added, and the mixture was stirred at r.t. for 60 h then evaporated under vacuum. Yields were determined by 1H NMR analysis in acetone-d6 with Ph3CH as an internal reference. The mixture was purified by semi-preparative TLC on silica gel (cyclohexane-EtOAc, 90:10) and analyzed by chiral column chromatography. In all cases, the NMR spectra were the same as those obtained in full analyses of the products. |
61 % ee | With (R)-2-(tert-butylsulfonyl)-6-chloro-2′-iodo-1,1′-biphenyl; 3-chloro-benzenecarboperoxoic acid In ethyl acetate at 20℃; for 72h; Inert atmosphere; Overall yield = 50%; Overall yield = 15.9 mg; enantioselective reaction; | |
80 % ee | With methyl N-(2-iodo-4,6-dimethylphenyl)-N-tosylalaninate; 3-chloro-benzenecarboperoxoic acid In dichloromethane; ethyl acetate at 20℃; for 72h; Overall yield = 91 percent; Overall yield = 78 mg; stereoselective reaction; | |
77 % ee | With methyl N-(2-iodo-4,6-dimethylphenyl)-N-tosylalaninate; 3-chloro-benzenecarboperoxoic acid In dichloromethane; acetonitrile at 20℃; for 72h; Overall yield = 94 percent; Overall yield = 81 mg; stereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With tetrakis(acetonitrile)copper(I) perchlorate; 1,2-phenylenebis(diphenylphosphine oxide); lithium tert-butoxide; (R,R)-1,2-bis(2,5-diphenylphospholanyl)ethane In tetrahydrofuran; isopropyl alcohol at -60 - -40℃; for 72h; Inert atmosphere; enantioselective reaction; | 4.1. General procedure General procedure: Preparation of Li(OC6H4-p-OMe) in THF: A flame-dried 20 mL test tube equipped with a magnetic stirring bar and a 3-way-stopcock was charged with p-methoxyphenol (12.4 mg, 0.1 mmol) in a dry box. Dry THF (1.0 mL) was added via a syringe with a stainless steelneedle. To the solution was added n-BuLi (62.5 μL, 0.1 mmol, 1.6 M in n-hexane) at 0 °C and stirred at the same temperature for 1 h to give a 0.1 M lithium p-methoxyphenoxide solution in THF, which was used within 30 min. Preparation of the catalyst solution:1 To a flame-dried 20 mL test tube equipped with a magnetic stirring bar and a 3-way glass stopcock was charged with[Cu(CH3CN)4]ClO4, (32.7 mg, 0.1 mmol), (R,R)-Ph-BPE (50.7 mg, 0.1 mmol), and phosphine oxide 5 (47.8 mg, 0.1 mmol)in dry box. To the flask dry THF (500 μL) was added via a stainless steel needle and a syringe, and the resulting solution was stirred at room temperature for 10 min to give yellow 0.2 M catalyst solution in THF, which was usedimmediately. A flame-dried 20 mL test tube equipped with a magnetic stirring bar and a 3-way glass stopcock was charged with dry THF (0.9 mL) was added via a syringe with a stainless---steel needle. Then, allyl cyanide 2 (161 μL, 2.0 mmol), ketone 1(1.0 mmol) and a premixed solution of [Cu(CH3CN)4]ClO4, (R,R)-Ph-BPE, and phosphine oxide 5 in THF (50 μL, 0.01mmol, 0.2 M). The test tube was immersed into an electronically-controlled cooling bath at -60 °C with 2-propanol as medium. To the solution was added lithium p-methoxyphenoxide (0.1 M/THF, 100 μL, 0.01 mmol) and stirring was continued at -40 °C for 40 h. The reaction was quenched with sat. aq. NH4Cl and the biphasic mixture was extracted with EtOAc. The combined organic layers were washed with brine and dried over Na2SO4. After evaporation of the solvent under reduced pressure, the crude mixture was purified by silica gel column chromatography to give the desired product. |
67% | With tetrakis(acetonitrile)copper(I) perchlorate; 1,2-phenylenebis(diphenylphosphine oxide); lithium tert-butoxide; (R,R)-1,2-bis(2,5-diphenylphospholanyl)ethane In tetrahydrofuran at -40℃; for 72h; Inert atmosphere; optical yield given as %ee; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39% | In tetrahydrofuran; at 20℃; for 1h; | Step 1: N-Methoxy-N-methylbenzamide (43 g, 0.259 mmol) was dissolved in 200 mL THF, and then propylmagnesium bromide (42.3 g, 0.288 mol) was added dropwise. The reaction mixture is stirred at room temperature for one hour. The mixture was poured into water and extracted with EA, and the organic phase is separated. Dried over sodium sulfate and evaporated. The residue, 1-phenylbutan-1-one, was purified by chromatography (PE: EA=IO: 1). Yield (15 g, 39%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: diethyl iodomethanephosphonate With potassium hexamethylsilazane In tetrahydrofuran at -78℃; for 2h; Inert atmosphere; Stage #2: propiophenone In tetrahydrofuran at -78 - 0℃; Inert atmosphere; | General procedure for gem-diiodoalkene derivatives General Procedure: An Ar-purged two-necked flask containing a solution of KHMDS (499 mg, 2.50 mmol) in THF (10 mL) was cooled to -78 °C and then a solution of (iodomethyl)phosphonic acid diethyl ester (1.39 g, 5.00 mmol) in THF (2 mL) was added. After steering at this temperature for 2 h, a solution of the ketone (2.00 mmol) in THF (1 mL) was added to the reaction mixture at -78 °C. The reaction mixture was wormed up to 0 °C and monitored by TLC or GC. When the reaction was complete, the reaction mixture was carefully diluted with water. The resulting mixture was extracted several times with EtOAc and the organic fraction was then washed with brine and dried over MgSO4. After removal of the solvent under reduced pressure, the residue was purified by chromatography on SiO2 to give the corresponding gem-diiodoalkene derivative. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (thiophene-2-(N-diphenylphosphino)methylamine)(η5-pentamethylcyclopentadienyl)dichloroiridium(III); potassium hydroxide at 82℃; for 8h; Inert atmosphere; | ||
With [rhodium(I)((Ph2P)2N-C6H4-4-CH(CH3)2)(1,5-cyclooctadiene)](tetrafluoroborate); sodium hydroxide at 82℃; for 0.25h; Reflux; Inert atmosphere; Schlenk technique; | General procedure for the transfer hydrogenation of ketones General procedure: Typical procedure for the catalytic hydrogen transfer reaction: asolution of ruthenium complexes the [Rh((Ph2P)2NCH2-C4H3S)2]-BF4, 5, [Rh((Ph2P)2NCH2-C4H3O)2]BF4, 6, Rh((Ph2P)2N-C6H4-2-CH(CH3)2)(cod)]BF4, 7, [Rh((Ph2P)2N-C6H4-4-CH(CH3)2)(cod)]BF4,8, [Rh((Ph2P)2N-C6H4-2-CH(CH3)2)2]BF4, 9 or [Rh((Ph2P)2N-C6H4-4-CH(CH3)2)2]BF4, 10, NaOH (0.025 mmol) and the corresponding ketone (0.5 mmol) in degassed iso-PrOH (5 mL) were refluxed until the reactions were completed. After this period a sample of the reaction mixture was taken off, diluted with acetone and analyzed immediately by GC. Conversions obtained are related to the residual unreacted ketone. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With C52H58N4P2; isopropyl alcohol; triiron dodecacarbonyl; potassium hydroxide at 65℃; for 1h; Inert atmosphere; enantioselective reaction; | ||
Multi-step reaction with 2 steps 1: sodium tetrahydroborate / ethanol / Inert atmosphere 2: bis(1,5-cyclooctadiene)diiridium(I) dichloride; bis(triphenylphosphine)iminium chloride; acetone; potassium hydroxide; N,N'-bis[o-(diphenylphosphino)benzylidene]-(1S,2S)-diaiminocyclohexane / dichloromethane; water; isopropyl alcohol / 24 h / 28 °C / Resolution of racemate; Inert atmosphere | ||
99.2 % ee | With dichloro(benzene)ruthenium(II) dimer; C78H116N2O2P2Ru; hydrogen; sodium hydroxide In isopropyl alcohol at 40℃; for 12h; Inert atmosphere; Autoclave; | 31 Preparation of 1-phenylbutynol from 1-phenylbutan-1-one Example 31 Preparation of 1-phenylbutynol from 1-phenylbutan-1-one Benzeneruthenium(II) chloride dimer (1.0 mg, 2 μmol, 0.5 mol %) and a chiral ligand (M=Ru, R=t-Bu, Ar=3,5-t-Bu2C6H3-, 2.6 μmol, 0.65 mol %) were dissolved in i-propanol (3 mL) under nitrogen atmosphere, and then heated and stirred for 1 h at 85° C. After the mixture was cooled to room temperature, 1-phenylbutan-1-one (0.4 mmol), i-propanol (2 mL) and a solution of sodium hydroxide in i-propanol (0.4 mL, 0.4 M) were added thereto. Thereafter, the reaction system were placed in an autoclave, and stirred for 12 h under H2 (10 atm) at 40° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent:ethyl acetate/petroleum ether=1/8). Accordingly, pure 1-phenylbutynol was obtained and the ee value (ee=99.2%) was measured by GC analysis. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With 3-n-butyl-1,2-dimethyl-1H-imidazol-3-ium imidazolate at 60℃; for 20h; Inert atmosphere; | 6 Example 6: 3-ethyl-2-phenyl-1,8-naphthyridine After replacing N2 in a 50mL three-necked flask three times, add 2-amino-3-pyridinecarboxaldehyde (122.1mg, 1mmol), phenbutanone (192.7mg, 1.3mmol), ionic liquid [Bmmim][Im] (7g), add another stirring rotor, close the feed port, put the reaction flask in an oil bath with magnetic stirring, and react at 60°C for 20 hours. After the reaction, N2 was slowly released, and the reaction solution was extracted with deionized water and ethyl acetate. The ethyl acetate layer was moved to a 7 cm high silica gel column, and the product was extracted and separated with a 30:1 developing solvent of petroleum ether: ethyl acetate, and the reaction yield was 93%. |
90% | With potassium <i>tert</i>-butylate In ethanol at 50℃; for 2h; | |
With potassium hydroxide In ethanol at 90℃; | 6 Example 6:; 3-Ethyl-2-phenyl- 1 ,8-naphthyridine; A mixture of 2-aminonicotinaldehyde (3.00 g, 24.6 mmol) and butyrophenone (3.64 g, 1.00 eq) in EtOH (100 mL) was treated with KOH (200 mg, 0.140 eq) in EtOH (15 mL) dropwise. The resulted reaction mixture was heated at 90 °C overnight. The solvent was removed and the residue was treated with ethyl Et20 to give a white crystalline material as the titled compound. 1H-NMR (400 Hz,CDCls) δ ppm 1.27 (3H, t, J=8.0 Hz), 2.94 (2H, q, J=8.0 Hz), 7.46-7.54 (4H, m), 7.66-7.69 (2H, m), 8.14 (1H, s), 8.27 (1H, d, J=8.0 Hz), 9.13 (1H, d, J=4.0 Hz). Mass Spectrum (ESI) m/e = 235 (M + 1). |
With potassium <i>tert</i>-butylate In ethanol at 50℃; for 2h; | ||
With potassium <i>tert</i>-butylate In ethanol at 50℃; for 5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | Stage #1: propiophenone With 2,6-bis[(4,4-dimethyl)-2-oxazolin-2-yl]pyridine copper bromide In dimethyl sulfoxide at 20℃; for 0.166667h; Green chemistry; Stage #2: morpholine In dimethyl sulfoxide at 20℃; for 10h; Green chemistry; | |
94% | With 2,6-bis[(4,4-dimethyl)-2-oxazolin-2-yl]pyridine copper bromide In dimethyl sulfoxide at 20℃; for 15h; | 5 preparation of α-morpholine butyrophenone In the air atmosphere,A polytetrafluoroethylene magnet was placed in the reactor,Was prepared by the procedure described in Example 1,6-bis [4- (1,1-dimethyl) _2-oxadiazolin-2-yl] pyridine bromide copper bromide reagent 0.06 mmol (5 mol%), 1.2 mmol of phenylbutanone,3.6 mmo of morpholine and 1.2 ml of dimethyl sulfoxide solvent,Room temperature conditions,Stir for 15 h. The reaction mixture was purified by silica gel column chromatography using ethyl acetate / n-hexane eluent,To give α-morpholine benzophenone compound (0.26 g, yield 94%),Its knot |
70% | With tert.-butylhydroperoxide; N-iodo-succinimide In water; acetonitrile at 20℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With triethylamine In neat (no solvent) at 20 - 40℃; for 2h; Green chemistry; | General Procedure for the Synthesis of Compounds 3a-3q General procedure: A mixture of substituted ketones 1 (11 mmol), phosphite 2 (10 mmol), and triethylamine(10 mmol) were stirred from ambient temperature to 40 °C for 2 h. The crude product was collected by filtration and recrystallized from ethyl acetate to afford pureα-hydroxyphosphonates 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With cerium(III) chloride heptahydrate; oxygen; sodium iodide In ethanol at 80℃; Sealed tube; | 3.1.6. Procedure for the Synthesis of AI-27 The butyrophenone (0.5 mmol) and 2-aminopyridine (0.5 mmol) were dissolved in EtOH (1 mL)at 80 C in a 35 mL sealed tube, and then CeCl37H2O/NaI (0.05 mmol, 10 mol %) was added.The reaction proceeded under an O2 atmosphere for the indicated time until complete consumption ofthe starting material as indicated by TLC. The solution was diluted with EtOAc (10 mL) and washedwith H2O (3 10 mL). Then, the organic layer was separated and concentrated under vacuum, andthe crude product was purified by column chromatography (petroleum ether/EtOAc) to provide thefinal product AI-27 [24]. |
62% | With copper(l) iodide; oxygen; copper(ll) bromide In 1-methyl-pyrrolidin-2-one at 100℃; for 30h; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | Stage #1: propiophenone With 2,6-bis[(4,4-dimethyl)-2-oxazolin-2-yl]pyridine copper bromide In dimethyl sulfoxide at 20℃; for 0.166667h; Green chemistry; Stage #2: Thiomorpholin In dimethyl sulfoxide at 20℃; for 10h; Green chemistry; | |
89% | With 2,6-bis[(4,4-dimethyl)-2-oxazolin-2-yl]pyridine copper bromide In dimethyl sulfoxide at 20℃; for 15h; | 12 preparation of α-Thiomorpholine Butyrophenone compound In the air atmosphere, a polytetrafluoroethylene magnet granule was placed in the reactor, then added 2-6-bis [4- (1,1-dimethyl) -2-oxazolin-2-yl] pyridine and Cupric bromide reagent (0.06mmol (5mol%) prepared by the method of Example 1 , 1.2 mmol of Butyrophenone, 3.6 mmol of Thiomorpholine and 1.2 ml of dimethyl sulfoxide solvent and at room temperate carried out open stirring for 15h. The reaction mixture was subjected to silica gel column chromatography using ethyl acetate / n-hexane eluent to give α-Thiomorpholine Butyrophenone compound (0.27g, yield 89%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With nickel(II) iodide; 2,6-bis((S)-4-isopropyl-4,5-dihydrooxazol-2-yl)pyridine; zinc In N,N-dimethyl-formamide at 20℃; Schlenk technique; Inert atmosphere; | Nickel-Catalyzed Allylation of Ketones; General Procedure General procedure: A flame-dried Schlenk tube was charged with ligand 2 (6.3 mg,0.021 mmol, 7 mol%) and activated Zn powder (59.2 mg, 0.900mmol, 300 mol%). The tube was capped with a rubber septum andmoved into a glove box, at which point NiI2 (4.7 mg, 0.015 mmol,5 mol%) was added. DMF (0.5 mL), the respective ketone (0.300mmol, 100 mol%), and the allylic carbonate (0.450 mmol, 150mol%) were added via syringe. The reaction mixture was allowedto stir overnight under an N2 atmosphere at r.t. The mixture was directlyloaded onto a silica column without workup. The residue inthe reaction vessel was rinsed with a small amount of CH2Cl2 or eluent.Flash column chromatography (eluent: 5-40% EtOAc in PE)provided the product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 85% 2: 10% | With sodium tetrahydroborate; nickel(II) chloride hexahydrate In methanol for 8h; Reflux; chemoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With ferrous(II) sulfate heptahydrate; benzyl seleninic acid In ethyl acetate at 60℃; for 24h; Green chemistry; | |
73% | With N-hydroxyphthalimide; benzeneseleninic acid In dichloromethane at 80℃; for 48h; Sealed tube; Green chemistry; | 2.2 General procedure for the PhSe(O)OH/NHPI-catalyzed aerobic oxidative deoximation reactions General procedure: To a 100 mL reaction tube equipped with a piece of magnetic bar, 0.5 mmol of oxime 1, 0.075 mmol of PhSe(O)OH, 0.05 mmol of NHPI and 1 mL of DMC were subsequently added. The tube was then sealed with PTFE screw plug and magnetically stirred at 80 °C for 48 h (Safety warning: the reaction tube was made of thick glass and could endure at least 7 atmosphere pressures). After cooling to room temperature, the solvent was removed by rotatory evaporator, and the residue was subjected to flash column chromatography on silica gel (Silica gel G) to give the related carbonyl product 2 (eluent: petroleum ether/EtOAc=10:1). |
67% | With dibenzyl diselenide; dihydrogen peroxide In acetonitrile at 60℃; for 24h; |
94 %Chromat. | With wool supported manganese dioxide nanoparticles at 20℃; for 7h; | |
With Manganese dioxide nanostructures coated on natural silk at 20℃; for 0.0833333h; | 3.4. Oxidation of oximes; General procedure General procedure: An oxime (1.0 mmol) and MnO2silk (0.09 g, 10 mol% of MnO2)were well ground using a pestle at room temperature. The progressof the reaction was monitored by TLC and GC. After completion ofthe reaction, the solid was washed with dichloromethane. After thefiltration of the reaction mixture, analysis of the filtrate has beendone by GC method. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With potassium carbonate In neat (no solvent) at 20 - 50℃; for 4h; Green chemistry; | General Procedure for the Synthesis of Compounds 3a-3m General procedure: A mixture of ketones 1 (21 mmol), phosphite 2 (20 mmol), and potassium carbonate(20 mmol) was stirred from ambient temperature to 50C within 4 h. The crude productwas washed with water (3 × 20 mL), extracted with CH2Cl2 (3 × 10 mL). The extract waswashed with brine (30 mL), dried over anhydrous sodium sulfate, and evaporated underreduced pressure to give a solid, which was recrystallized from ethyl acetate to afford pureα-hydroxyphosphonates 3. Sample 1H, 13C, and 31P NMR spectra for 3a, 3h, and 3j arepresented in the online Supplemental Materials (Figures S1-S9). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With 4-methylbenzenesulfonic acid-based ionic liquid supported on silica gel In ethanol at 20℃; for 6h; | 2.3 General Procedure for the Synthesis of Indoles General procedure: To a solution of phenylhydrazine (10 mmol) and ketone or aldehyde (10 mmol) in ethanol (15 mL) was added catalyst IL-SO3H-SiO2 (1.2 g). The mixture was allowed to stirringat room temperature for a period time specified in Table 2.The reaction was monitored by TLC and GC. After completionof the reaction, the catalyst was recovered by filtration.Evaporation of the solvent under reduced pressuregave the crude product. Further purification was achievedby flash column chromatography on a silica gel to give thedesired product. The recovered catalyst was dried andreused for the next run. Spectroscopic data for selectedproducts is as follows. |
With trifluoroacetic acid at 73℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With [(copper(II))0.5(lanthanum(III))2(monoacid 3,5-pyridinedicarboxylate)(3,5-pyridinedicarboxylate)2(sulfate)(H2O)2] monohydrate; oxygen In neat (no solvent) at 120℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95.3% | With cobalt(II) chloride hexahydrate; [bis(acetoxy)iodo]benzene; N-ethyl-N,N-diisopropylamine; 1-butyl-methylpyrrolidinium bis(trifluoromethylsulfonyl)amide In dimethyl sulfoxide; acetonitrile at 65℃; for 9h; | 4 To an appropriate amount of an organic solvent (a mixture of DMSO and acetonitrile in a volume ratio of 2: 1) in an air atmosphere, Join 100 mmol of the compound of formula (I) 190 mmol of the compound of formula (II) 13.5 mmol of catalyst 9 mmol tetrazolium tetracarbonyl dichloride and 4.5 mmol of a mixture of cobalt chloride hexahydrate), 120 mmol Oxidant PhI (TFA) 2,27 mmol of the additive N-n-butyl-N-methylpyrrolidine bis (trifluoromethanesulfonyl) imide salt and 140 mmol base DIPEA, and then raised to 65 ° C, And the reaction was stirred at that temperature for 9 hours; After completion of the reaction, the reaction system was allowed to cool to room temperature, filtered, and the filtrate was sufficiently washed with saturated brine; Followed by addition of chloroform for 2-3 times. The organic phases were combined and concentrated under reduced pressure. The residue was purified by flash silica gel column chromatography using an equal volume of a mixed solvent of acetone and petroleum ether as the eluent to obtain the compound of the above formula (III) , The yield was 95.3%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With hydrogenchloride; In methanol; water; | General procedure: A stirred suspension of <strong>[16182-15-3]N-(2,4,6-trimethylbenzenesulfonyl)hydrazine</strong> (S11, 5.35 g, 25 mmol) in methanol (25 mL) was treated with conc. HCl (0.5 mL) and then slowly with acetophenone (S12a, 2.4 mL, 20 mmol). The precipitated product was isolated by filtration; its quick recrystallization from ethanol (ca. 65 mL) gave the pure, colorless needles of S13a (4.74 g, 75%) with mp 133.5-134.0 C (decomposition). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 75% 2: 10% | With [Ru(P(NOH)2)Cl2(PPh3)]; potassium <i>tert</i>-butylate In toluene at 150℃; for 24h; Schlenk technique; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With rhodium(III) chloride; hydrogen In 2,2,2-trifluoroethanol at 100℃; for 10h; chemoselective reaction; | |
With hydrogen In 1,3,5-trimethyl-benzene at 175℃; for 16h; | ||
> 99 %Chromat. | With hydrogen In n-heptane at 100℃; for 18h; Autoclave; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With tetrakis(triphenylphosphine) palladium(0); potassium acetate; silver fluoride; triphenylphosphine In hexane at 140℃; for 20h; Sealed tube; Inert atmosphere; | 17.1-17.3 In this embodiment, a preparation method of a benzoyl para-difluoroalkylated derivative is shown in the following steps: using phenylbutanone as a raw material, the reaction formula is as follows: (1) Add benzophenone 0.0296 g (0.2 mmol) and tetrakistriphenylphosphine palladium 0.0116 g to the reaction tube.(0.01 mmol), potassium acetate 0.0786 g (0.8 mmol), triphenylphosphine 0.0157 g (0.06 mmol), silver fluoride 0.0077 g (0.06 mmol), ethyl bromodifluoroacetate 0.0203 g (1.00 mmol) and 0.25 mL Hexane, protected by argon, and reacted at 140 ° C for 20 hours;(2) TLC tracks the reaction until it is completely over;(3) The crude product obtained after the completion of the reaction was separated by column chromatography (petroleum ether: ethyl acetate = 15:1) to obtain a target.Product (yield 65%). |
63% | With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; (2S,3S)-N-acetyl-2-amino-3-methylpentanoic acid; silver trifluoroacetate; sodium carbonate; <i>tert</i>-butylamine In 1,2-dichloro-ethane at 155℃; for 36h; Inert atmosphere; regioselective reaction; | General Experimental Procedure for the Synthesis of Corresponding Products General procedure: Mixture of 1 (0.2 mmol, 1.0 equiv), 2 (0.6 mmol, 3.0 equiv), [Ru(p-cymene)Cl2]2 (6.1 mg, 5 mol%), Na2CO3 (42.4 mg, 2.0 equiv), AgTFA (88.3 mg, 2.0 equiv), N-acetyl-L-isoleucine (10.3 mg, 30 mol%), 2-methylpropan-2-amine (11 μL, 0.5 equiv) and DCE (1.0 mL) in a reaction tube (15 mL) under argon atmosphere was heated at 155 °C for 36 hours. Upon completion, the reaction mixture was cooled to ambient temperature, filtered through a silica gel plug, and concentrated in vacuo. The crude reaction mixture was purified on silica gel using hexanes/EtOAc as the eluent to afford the desired product. |
55% | With tetrakis(triphenylphosphine) palladium(0); potassium acetate; silver fluoride; triphenylphosphine In hexane at 140℃; for 20h; Inert atmosphere; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With oxygen; sodium docusate; copper(l) chloride In water at 80℃; for 3h; Green chemistry; chemoselective reaction; | Typical procedure for the synthesis of N-(pyridin-2-yl)benzamide (3a) General procedure: The magnetically stirred mixture of the 2-amino pyridine 1a (112.9 mg, 1.2 mmol), acetophenone 2a (120.2 mg, 1 mmol, 1equiv), CuCl (10 mol%, 9.9 mg), sodium dioctylsulphosuccinate (SDOSS, 5 mol%, 22.2 mg) in water (2 mL) was heated at 80 oC while oxygen gas was bubbled into the mixture for 3 h. After completion of the reaction (TLC), the mixture was cooled to room temperature and diluted with EtOAc (10 mL), filtered by ordinary filter paper to recover the catalyst. The organic layer was washed with brine and dried over anhydrous Na2SO4. The filtrate was concentrated under rotary vacuum evaporation, and the residue was charged on to chromatography (100-200 mesh silica gel) column and eluted with EtOAc-hexane to afford pure 3a ( 170.4 mg, 86%). All the remaining reactions were performed following this general procedure. The spectral data of the synthesised compounds are provided below. |
43% | With tert.-butylhydroperoxide; trifluorormethanesulfonic acid; tetra-(n-butyl)ammonium iodide In water at 80℃; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Stage #1: propiophenone With magnesium methanolate; lithium diisopropyl amide In tetrahydrofuran; 1,2-dimethoxyethane; n-heptane; ethylbenzene at -30℃; for 0.0833333h; Inert atmosphere; Sealed tube; Stage #2: bis(pinacol)diborane In tetrahydrofuran; 1,2-dimethoxyethane; n-heptane; ethylbenzene at 150℃; for 12h; Inert atmosphere; Schlenk technique; Sealed tube; stereoselective reaction; | |
80% | Stage #1: propiophenone With magnesium methanolate; lithium diisopropyl amide In 1,2-dimethoxyethane at -30℃; for 0.0833333h; Inert atmosphere; Sealed tube; Stage #2: bis(pinacol)diborane In 1,2-dimethoxyethane at 130℃; for 12h; Inert atmosphere; | 1 Under a nitrogen atmosphere, add phenylbutanone (0.5mmol, 1.0equiv., 74.0mg), magnesium methoxide (1.0equiv., 43.2mg), ethylene glycol dimethyl ether (1.5mL) and magnets to the baked in the 25mL glass pressure tube. Subsequently, the glass pressure tube was cooled to -30°C, lithium diisopropylamide (1.1 equiv.) was added, and the mixture was stirred for 5 minutes. After the stirring was completed, the diboronic acid pinacol borate (1.2 equiv., 152.4 mg) was added at room temperature and the temperature was raised to 130° C. and stirred for 12 hours. After the reaction, ethyl acetate was added to the system for extraction, and the product was separated by column chromatography with a yield of 80% and Z:E>20:1. |
Stage #1: propiophenone With magnesium methanolate; lithium diisopropyl amide In tetrahydrofuran; 1,2-dimethoxyethane; n-heptane; ethylbenzene at -30℃; for 0.166667h; Inert atmosphere; Stage #2: bis(pinacol)diborane In tetrahydrofuran; 1,2-dimethoxyethane; n-heptane; ethylbenzene Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With monoethylene glycol diethyl ether at 90℃; for 12h; Green chemistry; | 2.1 General Procedure for the Synthesis of Ketones 2 with air General procedure: A mixture of alkene 1 (0.6 mmol), 1,2-diethoxyethane (0.5 mL, 3.6 mmol) was added to a 5 mL round-bottom flask with an air balloon at room temperature, then the contents were stirred at 90 °C for 12 hours. The progress of the reaction was monitored by TLC or GC-MS. Upon completion, the reaction was cooled down to room temperature. The resultant residue was purified by silica gel column chromatography to afford the desired product 2. |
78% | With tetrahydrofuran; oxygen In water at 20℃; for 18h; Irradiation; Green chemistry; | |
72% | With 1-hydroxy-pyrrolidine-2,5-dione; graphitic carbon nitride; oxygen In acetonitrile at 20℃; Inert atmosphere; Irradiation; |
20% | With iron(III) chloride; potassium sulfide; oxygen In N,N-dimethyl-formamide at 80℃; for 14h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | Stage #1: potassium selenocyanate With hydrogenchloride; sodium nitrite In water; acetonitrile for 0.333333h; Cooling with ice; Stage #2: propiophenone In water; acetonitrile at 20℃; for 48h; | 4.2. General procedure for the synthesis of selenocyanates General procedure: To a solution of acetonitrile (15 mL), aqueous hydrochloric acid (3 M, 5 mL) was added at 0 °C, following by the addition of aqueous sodium nitrite (0.104 g, 1.5 mmol, dissolved in 1.5 mL of distilled water). After stirred at the same temperature for 10 min, KSeCN (72.5 mg, 0.5 mmol) was added in one portion. The resulting solution was stirred at the ice bath for 20 min. Afterwards, carbonyl compound or electron-rich arene (0.5 mmol) was added and the reaction mixture was continuously stirred in room temperature until no starting material was observed (the progress was monitored by TLC). The solvent was removed, the residue was extracted with ethyl acetate and washed with brine. The combined organic phases were dried, concentrated and purified by flash column chromatography on silica gel to give pure target products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | Stage #1: (3,4-Dimethoxyphenyl)acetic acid With phosphoric acid; trifluoroacetic anhydride In acetonitrile at 25℃; for 0.5h; Stage #2: propiophenone In acetonitrile at 25 - 80℃; for 20h; | Synthesis of 3a′, 3a-x and 3aa-ag; General Procedure General procedure: Trifluoroacetic anhydride (TFAA, 230 mg, 1.1 mmol) and phosphoricacid (H3PO4, 110 mg, 1.1 mmol) were added to a solution of oxygenatedarylacetic acids 1a-d (1.0 mmol) in MeCN (15 mL) at 25 °C. The reactionmixture was stirred at 25 °C for 30 min. Ketone 2a-x or 2aa-ad(0.5 mmol) in MeCN (5 mL) was added to the reaction mixture at25 °C, and the reaction mixture was stirred at reflux (80 °C) for 20 h.The solvent of reaction mixture was concentrated, the residue was dilutedwith water (10 mL) and the mixture was extracted with CH2Cl2(3 × 20 mL). The combined organic layers were washed with brine,dried, filtered and evaporated to afford the crude product under reducedpressure. Purification on silica gel (hexanes/EtOAc = 10:1 to1:1) afforded compounds 3a′, 3a-x and 3aa-ag. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With chlorine[2-(4,5-dihydro-1H-imidazol-2-yl)-6-methoxypyridine](pentamethylcyclopentadienyl)iridium(III) chloride; potassium hydroxide In water at 80℃; Schlenk technique; Inert atmosphere; | 15 In a 10 mL Schlenk tube, add ethanol (1.1 mmol), phenethyl alcohol (1.0 mmol), KOH (1.1 mmol), H2O (2.0 mL) and TC-6 (0.1 mol%). Under the protection of nitrogen, heat to 80°C for reaction. After completion, it was extracted with ethyl acetate (3×5.0 mL), the organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure to obtain a crude product. The crude product was purified with a mixture of ethyl acetate/petroleum ether (1/50) as the eluent and purified by silica gel chromatography to obtain a pure product with a yield of 90%. |
90% | With chlorine[2-(4,5-dihydro-1H-imidazol-2-yl)-6-methoxypyridine](pentamethylcyclopentadienyl)iridium(III) chloride; potassium hydroxide In water at 80℃; for 16h; Schlenk technique; Inert atmosphere; chemoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; 4,4'-Dimethoxy-2,2'-bipyridin; cesiumhydroxide monohydrate; copper diacetate In acetonitrile at 120℃; for 48h; Schlenk technique; Sealed tube; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; 4,4'-Dimethoxy-2,2'-bipyridin; cesiumhydroxide monohydrate; copper diacetate In acetonitrile at 120℃; for 48h; Schlenk technique; Sealed tube; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | Stage #1: methanol; propiophenone With [pentamethylcyclopentadienyl*Ir(2,2′-bpyO)(OH)][Na]; caesium carbonate at 120℃; for 12h; Schlenk technique; Stage #2: With water at 120℃; for 12h; Schlenk technique; | 4.1. General synthesis of b-methylated secondary alcohols usingmethanol General procedure: In air, in a 25mL Schlenk tube were added ketone (1 mmol), cat. 9(5.5 mg, 1 mol%), Cs2CO3 (97.8 mg, 0.3 equiv), and MeOH (2 mL). Thereaction mixture was heated at 120 C in an oil bath for 12 h underairtight conditions. After cooling to ambient temperature, 2mL H2Owas added, and the mixture was heated at 120 C for another 12 h.After the given reaction time, the mixture was then cooled to ambienttemperature, concentrated under reduced pressure, and purifiedby flash column chromatography with hexanes/ethyl acetate(50/1-100/1, v/v) to afford the target product, which was identified by NMR analyses. All analytical data of the known compounds areconsistent with those reported in the literature. Some unknowncompounds are detected by NMR and HRMS analyses. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; tetreamethyl ammonium hydroxide; copper(II) bis(trifluoromethanesulfonate); triphenylphosphine In toluene at 100℃; for 24h; Green chemistry; | |
92% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; tetreamethyl ammonium hydroxide; copper(II) bis(trifluoromethanesulfonate); triphenylphosphine In toluene at 100℃; for 24h; | 1; 6-7 phenylbutanone (1.0 mmol) and benzyl azide (2.0 mmol) were dissolved in toluene (2 mL), followed by Cu(OTf)2(0.1 mol), TEMPO (0.4 mmol), PPh3(0.3 mmol) and TMAOH (0.1 mmol), then the temperature was raised to 100 °C and the reaction was stirred under air atmosphere for 24 h.After the reaction was completed, saturated brine and ethyl acetate were sequentially added to the mixture for extraction, liquid separation, and the organic phase was concentrated to obtain a crude product, which was purified by column with a yield of 92%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With tert.-butylhydroperoxide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; copper(II) oxide In lithium hydroxide monohydrate; toluene at 110℃; for 24h; Green chemistry; | |
79% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; tetreamethyl ammonium hydroxide; copper(II) bis(trifluoromethanesulfonate); triphenylphosphine In toluene at 100℃; for 22h; | 5 phenylbutanone (1.0 mmol) and ethyl azide (1.6 mmol) were dissolved in toluene (2 mL), Cu(OTf)2(0.2 mol), TEMPO (0.4 mmol), PPh3(0.27 mmol) were added successivelyand TMAOH (0.8 mmol) and then heated to 100 °C and stirred for 22 h under air atmosphere.After the reaction, saturated brine and ethyl acetate were sequentially added to the mixture for extraction, liquid separation, and the organic phase was concentrated to obtain a crude product, which was purified by column with a yield of 79%. |
Tags: 495-40-9 synthesis path| 495-40-9 SDS| 495-40-9 COA| 495-40-9 purity| 495-40-9 application| 495-40-9 NMR| 495-40-9 COA| 495-40-9 structure
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P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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