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CAS No. : | 590-90-9 | MDL No. : | MFCD00059005 |
Formula : | C4H8O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | LVSQXDHWDCMMRJ-UHFFFAOYSA-N |
M.W : | 88.11 | Pubchem ID : | 111509 |
Synonyms : |
|
Num. heavy atoms : | 6 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.75 |
Num. rotatable bonds : | 2 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 22.7 |
TPSA : | 37.3 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -7.41 cm/s |
Log Po/w (iLOGP) : | 0.71 |
Log Po/w (XLOGP3) : | -0.8 |
Log Po/w (WLOGP) : | -0.04 |
Log Po/w (MLOGP) : | -0.33 |
Log Po/w (SILICOS-IT) : | 0.13 |
Consensus Log Po/w : | -0.06 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 2.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | 0.25 |
Solubility : | 157.0 mg/ml ; 1.78 mol/l |
Class : | Highly soluble |
Log S (Ali) : | 0.5 |
Solubility : | 276.0 mg/ml ; 3.13 mol/l |
Class : | Highly soluble |
Log S (SILICOS-IT) : | -0.35 |
Solubility : | 39.4 mg/ml ; 0.448 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.0 |
Signal Word: | Danger | Class: | 3 |
Precautionary Statements: | P210-P403+P235 | UN#: | 1993 |
Hazard Statements: | H225 | Packing Group: | Ⅲ |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With D218 resin In toluene at 80 - 120℃; for 7 h; Large scale | 4) 1 kg of dry D218 resin was charged into the fluidized bed reactor.6kg of phenol and 1.2kg of toluene were put into the reaction kettle. The reactor was heated and the column was opened. The bottom of the reaction liquid was flowed through the resin layer and the temperature of the column was stable at 80 . Start dropping 78percent of the butanone alcohol 1.6kg, 1h drops finished.After 15 min of incubation, the reactor was heated to 120 ° C and the reaction was continued for 7 h.The yield of raspberry ketone was 65percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82.5 %Chromat. | With N,N,N-triethyl-N-(propanesulfonic acid)ammonium hydrogensulfate In neat (no solvent) at 50℃; for 1.5 h; | In a typical reaction, Phenol(1, 0.5 mol), IL (0.03 mol) were added into a threeneckedround bottom flask equipped with magneticstirrer and butanolone (2, 0.1 mol) and dripped intothe above solution slowly. The resulting mixture washeated to 50°C and magnetically stirred for 30 minwhen the drop was completed. After the reaction wascompleted (TLC detected), the upper organic phasewas separated from IL by decantation and analyzed viagas chromatography (GC), IL was recovered from theaqueous solution by removing water at 70°C undervacuum for 6 h, and used directly for the next run (seeScheme 2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.06 g | With thionyl chloride In dichloromethane at 20℃; | 4-Hydroxy-2-butanone (0.881 g; 10 mmol), 2 ml of DCM, and thionyl chloride (1.46 ml; 20 mmol) were charged in a reaction flask and stirred at rt overnight. The mixture was evaporated and dried by nitrogen flow to yield 1.06 g of 2-chlorobutan-2-one. 1 H-NMR (400 MHz, rfe-DMSO): δ 2.12 (s, 3H), 2.94 (t, 2H), 3.74 (t, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.45 g | With SEC-BUTYLAMINE; magnesium chloride In aq. phosphate buffer; dimethyl sulfoxide at 15℃; for 24 h; Enzymatic reaction | A mixture of 0.9 gm enzyme ECS-ATA-134 and 7.5 ml PLP solution was added to asol uti on of phosphate buffer (15 ml, of example 2), secondary butyl amine (20 ml) andmagnesium chloride (5 ml) followed Li addition of a substrate solution (0.6 gm 4-Hydroxy butanone in S ml Dimethyl sulfoxide). The reaction mixture was stirred at 1Sfor 24 hours. The reaction mixture was extracted with ethyl acetate and the solvent wasremav’ed by distillation to obtain (R)-3-aminobutan-1 -ol. Y ield: 0.45 gm, 100percent R-isomer. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With pyridinium p-toluenesulfonate In dichloromethane at 20℃; for 4h; | 4-(Tetrahydro-2H-pyran-2-yloxy)-butan-2-one (13). 4-(Tetrahydro-2H-pyran-2-yloxy)-butan-2-one (13).A solution of 4-hydroxy-2-butanone (12, 2.111 g, 23.96 mmol), dihydropyran(3.20 mL, 2.950 g, 33.07 mmol) and pyridinium p-toluene sulfonate (0.592 g, 2.36 mmol) was stirred in anhydrousCH2Cl2 (30 mL) at room temperature for 4 h. The reactionmixture was then concentrated by removal of the solvents in vacuo. The residue was dissolved in Et2O (50 mL).This was washed with saturated aqueous NaCl (40 mL) and H2O (10 mL),dried over anhydrous MgSO4, filtered and concentrated in vacuo to give 13 as a pale yellow liquid (4.069 g, 23.63 mmol, 99%). The 1H NMR spectrum of the crudeproduct was consistent with that reported in the literature4 and the material was used withoutfurther purification. |
92% | With toluene-4-sulfonic acid In dichloromethane at 0℃; for 1h; | |
83% | Stage #1: 3,4-dihydro-2<i>H</i>-pyran; 1-Hydroxy-3-butanone With toluene-4-sulfonic acid In dichloromethane; water at 0℃; for 2h; Stage #2: With sodium hydrogencarbonate for 0.5h; |
81% | With camphor-10-sulfonic acid In dichloromethane at 0℃; for 2.3h; | |
80% | With toluene-4-sulfonic acid In dichloromethane at 0℃; for 1h; | |
With hydrogenchloride |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With sodium bromate; sodium hydrogensulfite In water; acetonitrile at 20℃; for 4.25h; | |
90% | With 3,3-dimethyldioxirane In acetone | |
90% | With sodium bromate; sodium hydrogensulfite In acetonitrile for 2h; Heating; |
85% | With aluminum oxide; potassium ferrate(VI); copper(II) sulfate In benzene for 30h; Ambient temperature; | |
83% | With sodium bromite In acetic acid for 5h; Ambient temperature; | |
83% | With sodium bromite In water; acetic acid for 10h; Ambient temperature; | |
75% | With sodium molybdate; tetrabutyl-ammonium chloride; dihydrogen peroxide In di-isopropyl ether; water at 60℃; Large scale; | 1-10 Example 4 Step 1. Add 10,000 moles of 1,3-butanediol to the 3000 liter reactor. Catalyst sodium molybdate 200mol, auxiliary tetrabutylammonium chloride 200mol, 50,000 mol of water and 4000 mol of water-carrying diisopropyl ether, stir well, form a mixture, and raise the temperature to 60 ° C; Step two, While stirring, adding 12000 mol of hydrogen peroxide with a mass fraction of 30% to the mixed solution, at the same time, the water is distilled under reduced pressure, and the pressure in the system is 0.01 MPa. Controlling the rate of dropwise addition of hydrogen peroxide is consistent with the dehydration speed of vacuum distillation; Step three, When the content of 1,3-butanediol in the reaction vessel is not higher than 25% of the initial content by gas chromatography, the dropwise addition of hydrogen peroxide is stopped. Stirring was continued for 1.4 hours, and the temperature in the reaction kettle was controlled not higher than 60 ° C. Distilling the watering agent; Step four, The temperature of the control system is not higher than 60 ° C. Vacuum distillation to obtain 440kg of 4-hydroxy-2-butanone as the final product. The purity of the product gas phase detection is over 95%. The yield was 75%. 101 kg of 1,3-butanediol was recovered. |
72.5% | With sodium tungstate; dihydrogen peroxide In hexane; water at 65℃; for 1h; | 3 Example 3 Into a four-necked flask was added 1.3 g of butanediol 200 g, 5 g of sodium tungstate, 50 g of water,N-hexane 100g, then warmed to 65 ,Start dropping 30% hydrogen peroxide, while adding dehydration,Control of the dropping rate and the rate of distillation and dehydration basically the same (hydrogen peroxide dropping rate of 30mL / h, the rate of distillation dehydration 27mL / h).After dropping about 410 g of hydrogen peroxide, when the content of the chromatographic detection reagent is less than or equal to 5%Stop dropping hydrogen peroxide to continue stirring for 1 hour to control the temperature in the reaction vessel will be n-hexane distilled,Then the temperature in the reaction vessel was lowered to 63 ° C, the target product of the product was distilled off and sent for inspection. The target product was identified as 4-hydroxy-2-butanone by mass spectrometry and infrared detection.The final amount of distilled water 448g, 4-hydroxy-2-butanone 145g, yield 72.5%. |
65% | With aluminum oxide; barium manganate; copper(II) sulfate In benzene for 18h; Ambient temperature; | |
65% | With aluminum oxide; sodium bromite Ambient temperature; | |
61% | With [bis({2‐[bis(propan‐2‐yl)phosphanyl]ethyl})amine](borohydride)(carbonyl)(hydride)iron(II) In tetrahydrofuran at 120℃; for 24h; Glovebox; Schlenk technique; Inert atmosphere; | |
61% | With [bis({2‐[bis(propan‐2‐yl)phosphanyl]ethyl})amine](borohydride)(carbonyl)(hydride)iron(II) In toluene at 120℃; for 24h; Glovebox; Schlenk technique; Inert atmosphere; chemoselective reaction; | General Procedure for the Iron-Catalyzed Dehydrogenation of Alcohols General procedure: In a glovebox, a 50-mL flame-dried Schlenk flask equipped with a condenser was chargedwith an iron catalyst (25 μmol), an alcohol substrate (2.5 or 25 mmol), and 5 mLtoluene. The solution was stirred at 120 °C for a specific time under a constant N2flow. After the reaction, the solution was allowed to cool to room temperature,filtered through a short silica gel column, and eluted with THF. The resultingfiltrate was evaporated under vacuum to afford the pure product. |
52% | With HRu(1,3-bis(6'-methyl-2'-pyridylimino)isoindolate)(PPh<SUB>3</SUB>)<SUB>2</SUB> In toluene at 100℃; for 24h; Inert atmosphere; Schlenk technique; chemoselective reaction; | |
50% | With methyl nitrite; nitrogen(II) oxide at 22.85℃; Irradiation; | |
50% | With iodine; hydrazine hydrate; dimethyl sulfoxide In water; acetonitrile at 80℃; for 4.5h; | |
50% | Stage #1: 1.3-butanediol With titanium tetrachloride In chloroform at 20℃; for 1h; Molecular sieve; Stage #2: With tert.-butylhydroperoxide In chloroform; toluene for 48h; Reflux; chemoselective reaction; | |
41% | for 48h; Ambient temperature; buffer; electrooxidation: 28 mA current; | |
36% | With tert.-butylhydroperoxide; 3 A molecular sieve In 2,2,4-trimethylpentane Heating; | |
28% | at 120℃; | |
With copper at 200 - 220℃; | ||
With copper at 160 - 200℃; unter Verduennung mit Wasserdampf, Stickstoff oder Propan; | ||
With 3,3-dimethyldioxirane In acetone at 27℃; | ||
96 % Chromat. | With tert.-butylhydroperoxide; bis(acetylacetonate)oxovanadium In benzene at 80℃; for 24h; | |
With tert.-butylhydroperoxide; cetylpyridinium chloride; magnesium sulfate In benzene for 24h; Heating; Yield given; | ||
With tert.-butylhydroperoxide In benzene for 24h; Heating; Yield given; | ||
61 % Chromat. | With N-hydroxyphthalimide; oxygen; cobalt acetylacetonate In acetonitrile for 12h; Heating; | |
99 % Chromat. | With dihydrogen peroxide In acetonitrile at 80℃; for 12h; | |
83 %Chromat. | With 2,2'-azobis(isobutyronitrile); oxygen In acetonitrile at 100℃; for 8h; Autoclave; | |
With Pd(κ1-O-OAc)(η3-allyl)(κ1-C-((2,6-di-iso-propylphenyl)2(C3H2N2)) In dimethyl sulfoxide; toluene at 80℃; for 2h; Autoclave; chemoselective reaction; | ||
With 2C7H7O3S(1-)*C28H36N4Pd(2-); potassium carbonate In dimethyl sulfoxide; toluene at 80℃; for 2h; Autoclave; chemoselective reaction; | ||
In neat (no solvent) | ||
With Au/graphite; oxygen In water at 100℃; for 24h; | Butanediol oxidation General procedure: Reactions were carried out using a Radley’s low pressure glass reactor (50 ml). A butanediol in water (20 ml, 0.6 M) and the catalyst(butanediol/metal ratio2000) were added into the reactor,which was then pressurized with oxygen (3 bar). The reaction mixture was heated to 100 C for 24 h under constant stirring(1000 rpm), then cooled to room temperature and analyzed. 1H-NMR spectroscopy was used for product identification; spectrawere acquired over a 16 scan period using a Bruker 400 MHz DPXsystem with a 5 mm auto tune broadband probe. All samples were prepared as dilute solutions in D2O. Carbon mass balances were calculated and were between 96 and 104%. Blank reactions have also been carried out with no oxidation activity detected in the absence of catalyst or with the KB-B carbon support. | |
100 %Spectr. | With oxygen In water at 100℃; for 24h; | 4.2 Butanediol oxidation General procedure: (0017) Reactions were carried out using a Radley's low pressure glass reactor (50ml). A butanediol in water (20ml, 0.6M) and the catalyst (butanediol/metal ratio=2000) were added into the reactor, which was then pressurized with oxygen (3bar). The reaction mixture was heated to 100°C for 24h under constant stirring (1000rpm), then cooled to room temperature and analyzed. 1H NMR spectroscopy was used for product identification; spectra were acquired over a 16 scan period using a Bruker 400MHz DPX system with a 5mm auto tune broadband probe. All samples were prepared as dilute solutions in D2O. Carbon mass balances were calculated and were between 96 and 104%. Blank reactions have also been carried out with no oxidation activity detected in the absence of catalyst or with the KB-B carbon support. |
With 1-hydroxytetraphenylcyclopentadienyl(tetraphenyl-2,4-cyclopentadien-1-one)-μ-hydrotetracarbonyldiruthenium(II); cyclohexanone at 150℃; for 0.5h; | 3.3. Dehydrogenation of 1,3-diols using a hydrogen acceptor In an analogous experiment anhydrous 1,3-butanediol (0.19 mL,2.12 mmol), cyclohexanone (0.402 g, 4.10 mmol) and 1 (1.5 mg,2.6 mol) were combined, degassed, and heated to 150C in a J.Young valve adapted NMR tube for 30 min. The13C NMR spec-trum (peaks at = 208.65 (C O), 57.80 (CH2OH), 46.66 (CH2)and 30.38 (CH3) ppm, SI Fig. S-8) indicated formation of the-HK 4-hydroxybutanone as the only C4product (Eq. (5)). The1H NMR spectrum (peaks at = 4.65 (t, OHCH2CH2-), 3.625 (q,OHCH2CH2-), 2.53 (t, OHCH2CH2-), and 2.09 (s, (CO)CH3) ppm,SI Fig. S-9) confirmed the formation of this product according tothe SDBS database [15]. Integration of proton resonances, cali-brated to a benzene standard, gave the 4-hydroxybutanone yieldas 1.44 mmol (68% conversion and 746 catalyst turnovers). Reso-nances for cyclohexanol, 1,3-butanediol and cyclohexanone werealso evident in the13C and1H NMR spectra. Integration of pro-ton resonances gave a 1.87 mmol yield for the hydrogen transferproduct cyclohexanol. The1H NMR spectrum of 1,3-butanediol inDMSO-d6is shown in SI Fig. S-9. | |
98 %Spectr. | With iron(III) chloride; 1,1,1,3',3',3'-hexafluoro-propanol; oxygen; nitric acid at 20℃; for 22h; | |
at 320℃; Inert atmosphere; | 1-5; 7-8; 11 Example 5 Using the catalyst Y2 prepared in Example 2 as the precursor, 10 ml of Y2 was placed in a fixed bed reactor with an inner diameter of 10 mm, and a methyl vinyl ketone-nitrogen gas mixture containing 10% by volume of methyl vinyl ketone was used. , Treated for 10 hours at 350°C and 0.2 MPa to obtain catalyst Y2-2. First reduce the catalyst Y2-2 in a hydrogen atmosphere at 250°C for 5 hours. After the reduction is completed, switch to 1,3-butanediol directly as the raw material. At a temperature of 320°C, a pressure of 0.1 MPa and a liquid hourly space velocity of 1 h- Under the conditions of 1, the conversion reaction is carried out, the conversion rate of raw materials is 51.2%, the selectivity of 4-hydroxy-2-butanone product is 83.9%, and the product yield per pass is 43.0%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.06 g | With thionyl chloride; In dichloromethane; at 20℃; | 4-Hydroxy-2-butanone (0.881 g; 10 mmol), 2 ml of DCM, and thionyl chloride (1.46 ml; 20 mmol) were charged in a reaction flask and stirred at rt overnight. The mixture was evaporated and dried by nitrogen flow to yield 1.06 g of 2-chlorobutan-2-one. 1 H-NMR (400 MHz, rfe-DMSO): delta 2.12 (s, 3H), 2.94 (t, 2H), 3.74 (t, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.99 kg | With [NH2Me2][(RuCl((R)-segphos))2(mu-Cl)3]; hydrogen; In methanol; at 60℃; under 11251.1 - 22502.3 Torr; for 8h;Autoclave; Inert atmosphere; Large scale; | To 5L autoclave 4-hydroxy-2-butanone(2.5kg, 28.38mol), [Me 2 NH 2] [(RuCl ((R) -segphos) 2 (u-Cl) 3] (Takasago International Corp. )(4.67g, 0.0057mol), methanol (2.5L) was added, after nitrogen substitution, under hydrogenpressure (1.53MPa), and the mixture was stirred for 8 hours at 60 C. After cooling, theresulting nitrogen-substituted reaction solution (4.5kg). The reaction mixture is thenconcentrated under reduced pressure to obtain a concentrated solution of 2.56kg. The resultingvacuum distillation the concentrated solution (75 C87 C / 666.6133.3Pa) By, give the (R)-1,3- butanediol (1.99kg, 22.1mol) It was. The resulting (R) -1,3- butanediol induced intodibenzoate was measured by HPLC using an optically active column (Chiralcel OD-H), opticalpurity, met ee 98.8% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With hydrogen; sodium hydroxide In water at 25℃; for 1h; Autoclave; | 2.4; 3-7; 3; 4 4. Preparation of 1,3-butanediol 0.44 g (5 wt%) of the activated Raney Nickel prepared in Example 1, 5 ml of 1N NaOH, and 70 ml of distilled water were added to the prepared high-pressure reactor, and 8.8 g of 4-hydroxy-2-butanone Is added.Hydrogen gas is introduced into the high-pressure reactor, the air in the flask is replaced, and hydrogen is again pressurized to adjust the pressure to 10 bar. The mixture is stirred for 1 hour while maintaining the temperature at 25 ° C.After completion of the reaction, hydrogen gas was removed, and 1,3-butanediol was neutralized with 1N HCl.Finally, the solid was removed by filtration. The solid was sufficiently washed with distilled water, and the solvent of the collected filtrate was distilled under reduced pressure, and the residue was analyzed. |
91% | With Cp*Ir(6,6'-dionato-2,2'-bipyridine)(H2O); isopropyl alcohol In water at 82℃; for 6h; Inert atmosphere; Schlenk technique; chemoselective reaction; | |
83% | With potassium borohydride In tetrahydrofuran; water at 45℃; for 4h; Cooling with ice; | 1.2; 5.2 2. Reduction reaction and catalyst 4 g of the condensation product was placed in a 250 mL round bottom flask in an ice bath, and 50 mL of tetrahydrofuran/water (9:1 by volume) was added. Under stirring, it was dispersed in 50 mL of tetrahydrofuran/water (9:1 by volume). The suspension of KBH4 (1g) was added dropwise to the flask. After the addition, the temperature was slowly raised to 45 ° C, and stirring was continued for 4 h. After the reaction was completed, 20 mL of 10% dilute hydrochloric acid was added, and the solvent was removed by rotary evaporation, and 3× was added. 10 mL was extracted into diethyl ether, and the reduced product was collected, the conversion rate was 92%, and the yield was 83%; |
68% | With sodium tetrahydroborate In methanol at 0℃; for 0.5h; | 16.1 1St step: butane - 1, 3 - diol (16 B)Butane - 1, 3 - diol The 4 - hydroxy -2 - butanone (16 A) (3.6 g, 20.9 mmol), dissolved in methanol (20 ml) in, 0 °C adding sodium borohydride (0.79 g, 20.4 mmol), stirring 30 minutes. The reaction liquid concentrated under reduced pressure, the residue with silica gel column chromatography (ethyl acetate/petroleum ether (v/v)=1/20 - 1/1) separating and purifying, to obtain the title compound butane - 1, 3 - diol (16 B), colorless oily matter (2.5 g, yield 68%) |
With hydrogen In methanol at 20℃; for 6h; | 43 Complex 5A-j from Example 12 (2.8 mg; 0.0025 mmol; 0.005 equiv) and 1-hydroxy-3-butanone (45 μL; 0.5 mmol) were placed in a reaction vessel, which was pressurized with argon and vented five times. Argon-degassed methanol (5 mL) was added and the reaction mixture was pressurized with argon and vented five times and then pressurized to 20.7 barg (300 psig) with hydrogen and stirred at ambient temperature for 6 hours. The vessel was vented, then pressurized with argon and vented five times. Analysis of the reaction mixture by chiral GC indicated 99.2% conversion to 1,3-butanediol. The solvent was stripped and the residue was converted to the diacetate using acetic anhydride (0.14 mL; 1.5 mmol; 3 equiv) and triethylamine (0.28 mL; 2.0 mmol; 4 equiv) with a catalytic amount of DMAP in 2.5 mL of dichloromethane. Assay of the 1,3-diacetoxybutane thus produced indicated 81.8% ee of the (R)-enantiomer according to chiral GC analysis. Chiral GC [30 m×0.25 mm Cyclosil-B (J&W Scientific), 0.25 μm film thickness, 100° C. isothermal]: tR=8.82 min (1-hydroxy-3-butanone), tR=16.09 min (1,3-butanediol), tR 20.65 min [(S)-1,3-diacetoxybutane], tR=23.20 min [(R)-1,3-diacetoxybutane]. | |
78 %Spectr. | Stage #1: 1-Hydroxy-3-butanone With phenylsilane In dichloromethane at 25℃; for 5 - 7h; Stage #2: With sodium hydroxide In water | |
With hydrogen; acetic acid In tetrahydrofuran at 59.84℃; for 1h; Autoclave; | 2.3 Hydrogenation General procedure: To a 100mL autoclave, a singlesubstrate (MAA, AA, HB or 2O, 101mmol) for individualhydrogenation or a mixture of the substrate (AA, HB or 2O,50.5mmol) and MAA (50.5mmol) for competitive hydrogenationwas placed with acetic acid (0.2 mL) and TA-MRNi orMRNi (400 mg). Hydrogen was injected (10 MPa) and the autoclavewas heated to 333 K. Reciprocating shaking was appliedto initiate the catalytic reaction. The reaction time was limitedto 1 h with MRNi to obtain a low conversion of the substrate,while to 3h with TA-MRNi. The accuracy of the conversionwas estimated from reproducibility to be within 5% of theobserved one. The reaction mixture was separated from thecatalyst by decantation. NMR was used to determine the conversionof the substrate.Enantioselective hydrogenations of AA and HB were carriedout over TA-MRNi to confirm the reported enantioselectivityunder the previous reaction conditions, where the substrate(1.0 g), acetic acid (0.2 mL) and THF (10 mL) were used. Priorto determining enantioselectivity, the reaction products wereacetylated with acetic anhydride and pyridine. Enantiomericexcess of the products was determined with gas chromatography(Shimadzu GC-17A equipped with a CP-Chirasil DEXCBcapillary column). Enantiomeric excess (%ee) is defined as, %ee = 100 × ([R] - [S]/([R]+ [S] (1) where [R] and [S] denote the amounts of the (R)- and (S)-products. | |
With nickel at 50℃; Hydrogenation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonia; hydrogen; In ethanol; at 10 - 45℃; under 9750.98 Torr; for 20.0h;Autoclave; | Add 250.0g of absolute ethanol and 110.5g of 4-hydroxy-2-butanone to a 1L reaction flask. 85.3g of NH3 was passed in at 10 C. The reaction solution was transferred to an autoclave, and 8.0 g of Raney nickel was added.Nitrogen and hydrogen were replaced three times, pressurized to 1.3MPa with hydrogen, the mixture was stirred at 45 C for 20 hours. GC detection of 4-hydroxy-2-butanol was less than 1.0%. The product was filtered and concentrated under reduced pressure at 45 C in a water bath. The concentrated solution was dissolved in toluene and stirred at 110 C. for 4 hours. Water was separated to obtain a lower layer. After concentrating again in a water bath at 50 C, distillation under reduced pressure of -0.9 MPa was performed, and a fraction of 80-120 C was received. The fraction was diluted with 40 g of absolute ethanol, add dropwise to a 500ml reaction bottle containing 85.2g of absolute ethanol and 65.0g of L-mandelic acid. The solution was added dropwise for 1 hour and maintained at a temperature of 55 C, and then reacted at 75 C for 20 minutes. The temperature was slowly lowered for 24 hours to 12 C, a solid was precipitated and filtered to obtain a crude filter cake. Stir the crude product with 250.8 g of isopropanol at 85 C and slowly reduce the temperature to 13 C for 3 hours. Filter again to get a crude filter cake. The above-mentioned operation of beating crystal filtration was repeated three times in total. Drying gave 80.6 g of constant weight white crystals. A 250 ml reaction tank was charged with 60.0 g of methanol, 80.6 g of white crystals, and 56.4 g of a 30% sodium methoxide methanol solution. The reaction was refluxed at 65 C for 17 hours. The temperature was lowered to 3 C and stirred for 30 minutes. Filtration at 3 C and concentration at 37 C were repeated twice to obtain 43.0 g of a colorless liquid. Distillate under reduced pressure at 125 C and receive 80-120 C fractions. Yield: 28.0%, GC: 99.9%, ee value is greater than 99.9%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With iodine Destillation; | ||
With hydrogenchloride Destillation; | ||
With sulfuric acid Destillation; |
With disodium hydrogenphosphate Destillation; | ||
With phosphoric acid Destillation; | ||
With zinc(II) chloride | ||
With zinc(II) chloride | ||
With Phthalic acid dibutyl ester; iodine; hydroquinone at 160℃; | ||
With phosphoric acid In methanol; water at 20℃; for 0.5h; | 2 Example 2Preparation of 2-acetyl-naphtho[2 ,S-b]furan-4 ,9-dione (Compound XIII , method 1 ) Preparation of S-buten-2-one [0134] To an 1 L round-bottom flask, 600 ml of 4-hydroxy-2-butanone, 100 ml of water,50 ml of methanol and 20 ml of 85% phosphoric acid were added. The mixture was stirred at room temperature for 30 minutes, and then distilled under reduced pressure (150-200 mmHg). Fraction at the boiling point of 65-80°C was collected. To the collected fraction, 80 grams of sodium chloride was added. The resulting mixture was stirred at 4°C for 1 hour, and then top organic layer was separated with funnel, dried with anhydrous sodium sulfate, and place at 4°C for use. | |
With phosphoric acid In methanol; water at 20℃; for 0.5h; | 1.1 Preparation of 3-buten-2-one To an 1 L round-bottom flask, 600 ml of 4-hydroxy-2-butanone, 100 ml of water, 50 ml of methanol and 20 ml of 85% phosphoric acid were added. The mixture was stirred at room temperature for 30 minutes, and then distilled under reduced pressure (100-300 mmHg). Fraction at the boiling point of 65-80°C was collected. To the collected fraction, 80 grams of sodium chloride was added. The resulting mixture was stirred at 4°C for 1 hour, and then top organic layer was separated with funnel, dried with anhydrous sodium sulfate, and place at 4°C for use. | |
With phosphoric acid In methanol; water at 20℃; for 0.5h; | 1 Example 1 Preparation of 2-acetyl-naphtho[2,3-b]furan-4,9-dione (Compound VI) To an 1 L round-bottom flask, 600 ml of 4-hydroxy-2-butanone, 100 ml of water, 50 ml of methanol and 20 ml of 85% phosphoric acid were added. The mixture was stirred at room temperature for 30 minutes, and then distilled under reduced pressure (150-200 mmHg). Fraction at the boiling point of 65-80°C was collected. To the collected fraction, 80 grams of sodium chloride was added. The resulting mixture was stirred at 4°C for 1 hour, and then top organic layer was separated with funnel, dried with anhydrous sodium sulfate, and place at 4°C for use. To a 500 ml round-bottom flask containing 16.1 grams (0.23 mol, prepared above) of 3- buten-2-one and 40 ml of dichloromethane cooled in an ice-salt bath, 36.7 grams (0.23 mol) of bromine diluted in 10 ml of dichloromethane was added dropwise in 15 minutes. The mixture was washed with 50 ml of water, dried with anhydrous sodium sulfate, and evaporated to remove dichloromethane. 43.4 grams (0.19 mol) of the residue was transferred into a 1 L round-bottom flask, diluted with 40 ml of DMF and cooled in an ice-salt bath. While stirring vigorously, 27.3 grams (0.18 mol) of l,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) diluted with 50 ml of DMF was added dropwise in 15 minutes. To the mixture, 31.4 grams (0.18 mol) of 2 -hydroxy- 1 ,4- naphthoquinone was added, and the ice-salt bath was removed. While stirring vigorously and open in air, 34.5 grams (0.23 mol) of DBU diluted with 50 ml of DMF was added dropwise in 30 minutes at room temperature. After stirred for 4 hours, 500 ml of ice cooled water was added to the mixture. The crude product was filtered, washed with water, 5% aqueous sodium bicarbonate, water, 2% aqueous acetic acid solution, ice-cooled ethanol, successively. Pure product (14.6 grams, yield 36.5%) was obtained by crystallization in formic acid, and characterized by 1H NMR and mass spectrum. 1H NMR (in DMSO) δ 2.61(s, 3H), 7.91-7.95(m, 2H), 8.06(s, 1H), 8.13-8.17(m, 2H). Mass (M+H) is 241. | |
With phosphoric acid In methanol; water at 20℃; for 0.5h; | 2 Preparation of 3-buten-2-one Preparation of 3-buten-2-one [0146] To an 1 L round-bottom flask, 600 ml of 4-hydroxy-2-butanone, 100 ml of water, 50 ml of methanol and 20 ml of 85% phosphoric acid were added. The mixture was stirred at room temperature for 30 minutes, and then distilled under reduced pressure (150-200 mmHg). Fraction at the boiling point of 65-80° C. was collected. To the collected fraction, 80 grams of sodium chloride was added. The resulting mixture was stirred at 4° C. for 1 hour, and then top organic layer was separated with funnel, dried with anhydrous sodium sulfate, and place at 4° C. for use. | |
With phosphoric acid In methanol; water at 20℃; for 0.5h; | 1.1 Preparation of 3-buten-2-one To a 1 L round-bottom flask, 600 ml of 4-hydroxy-2-butanone, 100 ml of water, 50 ml of methanol and 20 ml of 85% phosphoric acid were added. The mixture was stirred at room temperature for 30 minutes, and then distilled under reduced pressure (100-300 mmHg), where a fraction at the boiling point of 65-80° C. was collected. To the collected fraction, 80 grams of sodium chloride was added. The resulting mixture was stirred at 4° C. for 1 hour, and then the top organic layer was separated with a funnel, dried with anhydrous sodium sulfate, and stored at 4° C. | |
With tert.-butylnitrite In dimethylsulfoxide-d6 at 20℃; for 2h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With triethylamine In tetrahydrofuran at 0 - 20℃; for 3h; | 11.1 Intermediate Production Example 11; Production of the intermediate compound 1 (1) To 400 ml of tetrahydrofuran in a reactor, 15.0 g ( 0 .17 mol) of 3-oxo-1-butanol and 26.3 g (0. 19 mol) of benzoyl chloride were dissolved, followed by drop-wise adding 20.6 g (0.20 mol) of triethylamine under ice-cooling. After the end of drop-wise addition, the reaction liquid was stirred at room temperature for 3 hours. Hydrochloric acid salt of triethylamine was filtered, followed by adding water to the filtrate and extracting with ethyl acetate. The organic layer was washed with water, a saturated aqueous solution of sodium carbonate, water and a saturated saline solution in this order, followed by drying over anhydrous magnesium sulfate and concentrating under reduced pressure. The residue was purified with silica gel column chromatography (ethyl acetate : hexane = 1 : 5 to 1 : 3) to obtain 31.5 g (yield: 96 %) of 3-oxobutylbenzoate.1H-NMR (CDCl3, TMS) δppm: 2.24 (3H, s), 2.91 (2H, t), 4.59 (2H, t), 7.44 (2H, t), 7.56 (1H, t), 8.01 (2H, d) |
69% | Stage #1: benzoyl chloride With pyridine; dmap In dichloromethane at -70℃; for 0.5h; Inert atmosphere; Stage #2: 1-Hydroxy-3-butanone In dichloromethane at -70 - 26℃; for 17h; | 1 Step 1: Preparation of 3-oxobutyl benzoate To a stirred solution of benzoyl chloride (0.396 L, 3405 mmol) in DCM (1 L) at -70 °C under nitrogen atmosphere was added pyridine (470 mL) drop-wise over a period of 1 h. After stirring for 30 min at same temperature, 4-hydroxybutan-2-one (250.0 g, 2837 mmol) in DCM (500 mL) was added dropwise over a period of 1 h. The reaction mixture was allowed to warm to 26 °C and then was stirred for 16 h. The progress of the reaction was monitored by TLC (S1O2, 30% EtOAc/Pet. Rf = 0.4). On completion, the reaction mixture was washed with water (2 x 1000 mL), IN HCI (2 x 500 mL) and then saturated NaHC03 solution (2 x 500 mL). The organic layer was dried over Na2SC>4, filtered and concentrated under reduced pressure to afford 3-oxobutyl benzoate as a pale-yellow liquid (400 g, yield = 69%). XH NMR (400 MHz, CHLOROFORM-d) d = 8.05 - 7.94 (m, 2H), 7.60 - 7.51 (m, 1H), 7.47 - 7.36 (m, 2H), 4.65 - 4.54 (t, 2H), 2.97 - 2.84 (t, 2H), 2.28 - 2.13 (s, 3H). HPLC purity = 94.1%. |
With pyridine In dichloromethane |
With dmap; triethylamine In dichloromethane | ||
Stage #1: benzoyl chloride With pyridine In dichloromethane at -70℃; for 1.5h; Inert atmosphere; Stage #2: 1-Hydroxy-3-butanone In dichloromethane at -70 - 26℃; for 17h; Inert atmosphere; | 1 Step 1 : Preparation of 3-oxobutyl benzoate To a stirred solution of benzoyl chloride (0.396 L, 3405 mmol) in DCM (1 L) at -70 °C under nitrogen atmosphere was added pyridine (470 mL) drop-wise over a period of 1 h. After stirring for 30 min at same temperature, 4-hydroxybutan-2-one (250.0 g, 2837 mmol) in DCM (500 mL) was added dropwise over a period of 1 h. The reaction mixture was allowed to warm to 26 °C and then was stirred for 16 h. The progress of the reaction was monitored by TLC (S1O2, 30% EtOAc/Pet. Rf = 0.4). On completion, the reaction mixture was washed with water (2 x 1000 mL), IN HCI (2 x 500 mL) and then saturated NaHC03 solution (2 x 500 mL). The organic layer was dried over Na2SC>4, filtered and concentrated under reduced pressure to afford 3-oxobutyl benzoate as a pale-yellow liquid (400 g, yield = 69%). XH NMR (400 MHz, CHLOROFORM-d) d = 8.05 - 7.94 (m, 2H), 7.60 - 7.51 (m, 1H), 7.47 - 7.36 (m, 2H), 4.65 - 4.54 (t, 2H), 2.97 - 2.84 (t, 2H), 2.28 - 2.13 (s, 3H). HPLC purity = 94.1%. | |
Stage #1: benzoyl chloride With pyridine; dmap In dichloromethane at -70℃; for 1h; Inert atmosphere; Stage #2: 1-Hydroxy-3-butanone In dichloromethane at 26℃; for 17h; Inert atmosphere; | Step 1: Preparation of 3-oxobutyl benzoate To a stirred solution of benzoyl chloride (0.396 L, 3405 mmol) in DCM (1 L) at -70 °C under nitrogen atmosphere was added pyridine (470 mL) drop-wise over a period of 1 h. After stirring for 30 min at same temperature, 4-hydroxybutan-2-one (250.0 g, 2837 mmol) in DCM (500 mL) was added dropwise over a period of 1 h. The reaction mixture was allowed to warm to 26 °C and then was stirred for 16 h. The progress of the reaction was monitored by TLC (S1O2, 30% EtOAc/Pet. Rf = 0.4). On completion, the reaction mixture was washed with water (2 x 1000 mL), IN HCI (2 x 500 mL) and then saturated NaHC03 solution (2 x 500 mL). The organic layer was dried over Na2S04, filtered and concentrated under reduced pressure to afford 3-oxobutyl benzoate as a pale-yellow liquid (400 g, yield = 69%). XH NMR (400 MHz, CHLOROFORM-d) d = 8.05 - 7.94 (m, 2H), 7.60 - 7.51 (m, 1H), 7.47 - 7.36 (m, 2H), 4.65 - 4.54 (t, 2H), 2.97 - 2.84 (t, 2H), 2.28 - 2.13 (s, 3H). HPLC purity = 94.1%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With iodine In dimethyl sulfoxide at 20℃; for 8h; Inert atmosphere; | 1 1. 4-(phenylamino)-2-butanone Add magnetons, 0.1 mmol I2, 1 mmol 4-hydroxy-2-butanone, 1 mmol aniline in a 25 mL reaction flask.And 2mL of dimethyl sulfoxide, the reaction system was reacted in a nitrogen atmosphere at room temperature for 8 hours, and the reaction liquid was extracted with water, and the organic layer was combined.Wash three times with saturated brine, dry over anhydrous sodium sulfate, de-solute under reduced pressure, and residue column chromatography (ethyl acetate / petroleumEther = 1:4) gave 4-(phenylamino)-2-butanone in a yield of 94% (153.2 mg).Yellow oil. |
94% | With iodine In dimethyl sulfoxide at 20℃; for 8h; | General experimental procedure General procedure: A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol 4-hydroxybutan-2-one, 10 mol% I2 (25.4 mg), 2mL DMSO. The resulting mixture was performed at room temperature for 8 h. After reaction was complete, the resulting mixturewas poured into water (20 mL) and extracted with ethyl acetate (3 x10 mL). The combined organic extracts were washed with brine (3 5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting residue was purified by silica gel columnchromatography (ethyl acetate/petroleum ether 1:20-1:4) to afford the desired products. |
88% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 12h; Inert atmosphere; | 1 1. 4- (phenylamino) -2-butanone General procedure: 1. 4- (phenylamino) -2-butanoneIn a 25mL reaction flask, add magnetons,0.2mmol TEMPO (2,2,6,6-tetramethylpiperidine oxide), 0.1mmol TBN (tert-butyl nitrite),1 mmol of 4-hydroxy-2-butanone, 1 mmol of aniline and 2 mL of dimethyl sulfoxide. The reaction system was reacted for 9 h at room temperature in a nitrogen atmosphere.The reaction solution was extracted with water, and the organic layers were combined, washed with saturated brine three times, and dried with anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was subjected to column chromatography (ethyl acetate / petroleum ether = 1: 4) to obtain 4- (phenylamino) -2-butanone in a yield of 83% (135.5 mg) as a yellow oil. |
83% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 9h; Inert atmosphere; Green chemistry; | |
66% | With tert.-butylhydroperoxide; palladium(II) trifluoroacetate In water; acetonitrile at 70℃; for 12h; | |
With hydrogenchloride |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With D218 resin In toluene at 80 - 120℃; for 7h; Large scale; | 2.4 4) 1 kg of dry D218 resin was charged into the fluidized bed reactor.6kg of phenol and 1.2kg of toluene were put into the reaction kettle. The reactor was heated and the column was opened. The bottom of the reaction liquid was flowed through the resin layer and the temperature of the column was stable at 80 . Start dropping 78% of the butanone alcohol 1.6kg, 1h drops finished.After 15 min of incubation, the reactor was heated to 120 ° C and the reaction was continued for 7 h.The yield of raspberry ketone was 65%. |
With aluminium trichloride |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | With iodine In dimethyl sulfoxide at 20℃; for 24h; | General experimental procedure General procedure: A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol 4-hydroxybutan-2-one, 10 mol% I2 (25.4 mg), 2mL DMSO. The resulting mixture was performed at room temperature for 8 h. After reaction was complete, the resulting mixturewas poured into water (20 mL) and extracted with ethyl acetate (3 x10 mL). The combined organic extracts were washed with brine (3 5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting residue was purified by silica gel columnchromatography (ethyl acetate/petroleum ether 1:20-1:4) to afford the desired products. |
40% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 9h; Inert atmosphere; Green chemistry; | |
With orthoarsenic acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With triethylamine In dichloromethane at 0 - 20℃; | |
94% | With triethylamine In diethyl ether | |
80% | With triethylamine In dichloromethane at 25℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen; acetic acid; In tetrahydrofuran; at 59.84℃; under 75007.5 Torr; for 3h;Autoclave; | General procedure: To a 100mL autoclave, a singlesubstrate (MAA, AA, HB or 2O, 101mmol) for individualhydrogenation or a mixture of the substrate (AA, HB or 2O,50.5mmol) and MAA (50.5mmol) for competitive hydrogenationwas placed with acetic acid (0.2 mL) and TA-MRNi orMRNi (400 mg). Hydrogen was injected (10 MPa) and the autoclavewas heated to 333 K. Reciprocating shaking was appliedto initiate the catalytic reaction. The reaction time was limitedto 1 h with MRNi to obtain a low conversion of the substrate,while to 3h with TA-MRNi. The accuracy of the conversionwas estimated from reproducibility to be within 5% of theobserved one. The reaction mixture was separated from thecatalyst by decantation. NMR was used to determine the conversionof the substrate.Enantioselective hydrogenations of AA and HB were carriedout over TA-MRNi to confirm the reported enantioselectivityunder the previous reaction conditions, where the substrate(1.0 g), acetic acid (0.2 mL) and THF (10 mL) were used. Priorto determining enantioselectivity, the reaction products wereacetylated with acetic anhydride and pyridine. Enantiomericexcess of the products was determined with gas chromatography(Shimadzu GC-17A equipped with a CP-Chirasil DEXCBcapillary column). Enantiomeric excess (%ee) is defined as, %ee = 100 × ([R] - [S]/([R]+ [S] (1) where [R] and [S] denote the amounts of the (R)- and (S)-products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With 1H-imidazole In dichloromethane at 20℃; for 18h; | 1 Step 1: 4-[tert-butyl(dimethyl)silyl]oxybutan-2-one A mixture of 4-hydroxy-2-butanone (1.0 g, 11.35 mmol), te/f-butyldimethylsilyl chloride (2.05 g, 13.62 mmol) and Imidazole (1.55 g, 22.70 mmol) in DCM (100 mL) was stirred at room temperature for 18 h. The reaction was quenched with aqueous NH4CI, the layers were separated and the aqueous layer was extracted with DCM. Purification by column chromatography (50g column, 5 to 15% EtOAc in cHex, 15 CV) gave 4-[tert- butyl(dimethyl)silyl]oxybutan-2-one (2.29 g, 100%, 1 1.32 mmol) as a colourless oil. 1 H NMR (Chloroform-d, 500 MHz): d 3.90 (2H, t, J 6.1 Hz), 2.63 (2H, t, J 6.1 Hz), 2.19 (3H, s), 0.89 (9H, s), 0.06 (6H, s). |
98% | With dmap; triethylamine In dichloromethane at 20℃; for 2h; | Synthesis of 4-((tert-butyldimethylsilyl)oxy)butan-2-one To a solution of 4-hydroxybutan-2-one (17, 10 g, 113.49 mmol), triethylamine (47.5 mL, 340.48 mmol) and DMAP (2.8 g, 22.69 mmol) in CH2Cl2 (280 mL) was added t-butyldimethylsilyl chloride (20.5 g, 136.18 mmol) at rt, and the mixture was stirred for 2 h. After an addition of water, the mixture was extracted with CH2Cl2 (300 mL X 3). The combined organic layer was dried over anhydrous Na2SO4, filtered with cotton and celite pad, and concentrated. Purification of the crude syrup by chromatography (silica-gel 150 g, n-hexane/EtOAc 4:1) afforded the TBS ether as a colorless oil (22.4 g, 98%). |
94% | With 1H-imidazole In dichloromethane for 1.5h; Inert atmosphere; |
93% | With 1H-imidazole In dichloromethane at 0 - 20℃; Inert atmosphere; | |
93% | With 1H-imidazole In dichloromethane at 0 - 20℃; Inert atmosphere; | |
93% | With 1H-imidazole In dichloromethane at 0 - 20℃; for 1h; Inert atmosphere; Schlenk technique; | |
93% | With 1H-imidazole In dichloromethane at 0 - 20℃; for 1h; Inert atmosphere; | |
92% | With dmap; triethylamine In dichloromethane at 20℃; for 1.5h; | Synthesis of 4-(tert-Butyldimethylsilyloxy)butan-2-one (8) To a solution of 4-hydroxy-2-butanone (1.00 mL, 1.02 g, 11.6 mmol, 1.0 equiv) in CH2Cl2 (25 mL) was added NEt3 (4.86 mL, 3.52 g, 34.8 mmol, 3.0 equiv), DMAP (284 mg, 2.32 mmol, 0.2 equiv) and TBSCl (2.10 g, 13.9 mmol, 1.2 equiv) sequentially. After 90 minutes, the reaction was quenched by the addition of water (10 mL), the layers were separated, and the aqueous layer was extracted with Et2O (3 × 20 mL). The combined organic layers were dried over Na2SO4, filtered and the volatile components were removed in vacuo. The crude product was purified by flash chromatography (3 × 15 cm, Pn-Et2O, 4:1), yielding the title compound as a colorless oil (2.17 g, 10.7 mmol, 92%). Rf= 0.80 (Pn-Et2O, 4:1) [KMnO4]. 1H NMR (400 MHz, CDCl3): δ = 0.05 [s, 6 H, Si(CH3)2], 0.88 [s, 9 H, SiC(CH3)3], 2.18 (s, 3 H, H-1), 2.62 (t, 3J = 6.4 Hz, 2 H, H-3), 3.89 (t, 3J = 6.4 Hz, 2 H, H-4). 13C NMR (100 MHz, CDCl3): δ = -5.3 [q, Si(CH3)2], 18.4 [s, SiC(CH3)3], 26.0 [q, SiC(CH3)3], 31.0 (q, C-1), 46.7 (t, C-3), 59.0 (t, C-4), 208.2 (s, C-2). |
91% | With 1H-imidazole In N,N-dimethyl-formamide at 20℃; | |
90% | With 1H-imidazole In N,N-dimethyl-formamide at 0 - 20℃; for 12h; | 4 Example 4 To a solution of 4-hydryoxy-2-butanone (273 μ, 3.00 mmol) in DMF (20 mL) were added fert-butylchlorodimethylsilane (559 mg, 3.60 mmol) and imidazole (490 mg, 7.20 mmol) at 0 °C, and the mixture was stirred at rt for 12 hr. After the addition of MeOH, the mixture was diluted with Et20 and washed with H20 (x3). The organic layer was washed with brine, dried (Na2S04), and evaporated. The residue was purified by silica gel column chromatography (5% AcOEt in hexane) to give 6 (548 mg, 90%) as a colorless liquid. 1H NMR (500 MHz, CDC13) δ 3.88 (t, 2H, CH2CH20, J= 6.3 Hz), 2.62 (t, 2H, CH2CH20, J= 6.3 Hz), 2.19 (s, 3H, CH3), 0.88 (s, 9Η, C(CH3)3), 0.05 (s, 6Η, Si(CH3)2); 13C NMR (125 MHz, CDC13) δ 208.2, 58.8, 46.5, 30.9, 25.8, 18.2, -5.5; HRMS (pos. ion ESI) m/z calcd for (M+Na)+ Ci0H22NaO2Si: 225.1287. Found: 225.1280. |
90% | With 1H-imidazole In N,N-dimethyl-formamide at 0 - 20℃; for 12h; Inert atmosphere; | 4.1.1.3 4-((tert-Butyldimethylsilyl)oxy)butan-2-one (6) To a solution of 4-hydryoxy-2-butanone (273μL, 3.0mmol) in DMF (20mL) was added tert-butylchlorodimethylsilane (559mg, 3.6mmol) and imidazole (490mg, 7.2mmol) at 0°C, and the mixture was stirred at room temperature for 12h. After the addition of MeOH, the mixture was diluted with Et2O and washed with H2O (x 3). The organic layer was washed with brine, dried with Na2SO4, and evaporated. The residue was purified by silica gel column chromatography (5% AcOEt in hexane) to give 6 (548mg, 90%) as a colorless liquid. 1H NMR (500MHz, CDCl3) δ 3.88 (t, 2H, CH2CH2O, J=6.3Hz), 2.62 (t, 2H, CH2CH2O, J=6.3Hz), 2.19 (s, 3H, CH3), 0.88 (s, 9H, C(CH3)3), 0.05 (s, 6H, Si(CH3)2); 13C NMR (125MHz, CDCl3) δ 208.2, 58.8, 46.5, 30.9, 25.8, 18.2, -5.5; HRMS (ESI) m/z calcd for [M+Na]+ C10H22NaO2Si: 225.1287, found: 225.1280. |
90% | With 1H-imidazole In N,N-dimethyl-formamide at 0 - 20℃; for 12h; Inert atmosphere; | 4.1.1.3 4-((tert-Butyldimethylsilyl)oxy)butan-2-one (6) To a solution of 4-hydryoxy-2-butanone (273μL, 3.0mmol) in DMF (20mL) was added tert-butylchlorodimethylsilane (559mg, 3.6mmol) and imidazole (490mg, 7.2mmol) at 0°C, and the mixture was stirred at room temperature for 12h. After the addition of MeOH, the mixture was diluted with Et2O and washed with H2O (x 3). The organic layer was washed with brine, dried with Na2SO4, and evaporated. The residue was purified by silica gel column chromatography (5% AcOEt in hexane) to give 6 (548mg, 90%) as a colorless liquid. 1H NMR (500MHz, CDCl3) δ 3.88 (t, 2H, CH2CH2O, J=6.3Hz), 2.62 (t, 2H, CH2CH2O, J=6.3Hz), 2.19 (s, 3H, CH3), 0.88 (s, 9H, C(CH3)3), 0.05 (s, 6H, Si(CH3)2); 13C NMR (125MHz, CDCl3) δ 208.2, 58.8, 46.5, 30.9, 25.8, 18.2, -5.5; HRMS (ESI) m/z calcd for [M+Na]+ C10H22NaO2Si: 225.1287, found: 225.1280. |
90% | With 1H-imidazole In dichloromethane | |
83% | With 1H-imidazole; dmap In dichloromethane at 0 - 20℃; | |
80% | Stage #1: 1-Hydroxy-3-butanone; tert-butyldimethylsilyl chloride With 1H-imidazole In dichloromethane at 0℃; for 6h; Stage #2: With methanol; sodium tetrahydroborate at 0℃; for 1h; | |
65% | With 1H-imidazole In dichloromethane at 20℃; for 18h; | |
With 1H-imidazole In N,N-dimethyl-formamide | ||
In dichloromethane Inert atmosphere; | ||
1.63 g | With dmap; triethylamine In dichloromethane at 20℃; Cooling with ice; | X-72.1 [Step 1] 4-[tert-Butyl(dimethyl)silyl]oxybutan-2-one To a solution of 4-hydroxybutan-2-one (881 mg) in dichloromethane (26 ml), triethylamine (4.2 ml), 4-dimethylaminopyridine (244 mg) and tert-butyldimethylchlorosilane (1.81 g) were added in this order under ice cooling, and the mixture was stirred overnight at room temperature. The reaction solution was diluted with dichloromethane, washed with water and saturated saline in this order and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue obtained was purified by silica gel column chromatography (n-hexane/ethyl acetate) to obtain the title compound (1.63 g). 1H-NMR (CDCl3) δ: 0.05 (6H, s), 0.88 (9H, s), 2.18 (3H, s), 2.62 (2H, t, J = 6.0 Hz), 3.89 (2H, t, J = 6.3 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | In toluene at 20℃; for 0.0833333h; | |
82% | With trityl tetrafluoroborate In tetrahydrofuran at 0 - 20℃; for 1h; | 4.9. 4-((4-Methoxybenzyl)Oxy)Butan-2-One (16) To a stirred solution of 4-hydroxy-2-butanone (1.1 mL ,12.8 mmol) in dry THF (20 mL)at 0 °C, 4-methoxybenzyl 2,2,2-trichloroacetimidate (2 mL, 10.7 mmol) and triphenylcarbeniumtetrafluoroborate (cat.) were added sequentially. The reaction was continued further for 1 h atroom temperature prior to quenching with the saturated NH4Cl solution (50 mL) and extracted withDCM (2 100 mL). The combined organic layers were washed with brine, dried over Na2SO4,and concentrated in vacuum. Purification by column chromatography (PE/EA = 6:1) affordedcompound 16 (1.8 g, 82%) as a colorless oil [14].1H NMR (400 MHz, CDCl3)δ 7.33-7.18 (m, 2H), 6.94-6.81 (m, 2H), 4.45 (s, 2H), 3.81 (s, 3H), 3.72(t, J = 6.3 Hz, 2H), 2.71 (t, J = 6.3 Hz, 2H), 2.18 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 207.51, 159.27,130.16, 129.42, 113.84, 72.91, 64.96, 55.31, 43.81, 30.48. HRMS (ESI+): calcd. for C12H16O3 [M + H]+,209.1172, found 209.1170. |
77% | With camphor-10-sulfonic acid In dichloromethane at 0℃; |
77% | With camphor-10-sulfonic acid In dichloromethane at 0℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With pyridine In dichloromethane for 4h; Cooling with ice; | 1 Add dichloromethane (135ml) to a 500ml flask,Pyridine (60ml),4-hydroxy-2-butanone (65ml),As for cooling in an ice bath,Dissolve p-toluenesulfonyl chloride (47.68g) in 70ml dichloromethane,Slowly add dropwise to the above mixed solution.The reaction mixture was reacted for 4h in an ice bath,The TLC board detects the reaction status.After the reaction, 1mol/L hydrochloric acid was added to the reaction solution,Remove the pyridine in the reaction solution, separate the liquids,After washing with 10% Na2CO3 solution and clear water twice, the solvent is removed by rotary evaporation to obtain 4-p-toluenesulfonyloxy-2-butanone.The yield was 98%. |
75% | With pyridine In dichloromethane at 0 - 20℃; | |
75% | With pyridine |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With NaCNBH3; In dichloromethane; | Example 14 Synthesis of 3-(1-methylindol-3-yl)-4-[3-(3-hydroxy-1-methylpropylamino)phenyl]-1H-pyrrole-2,5-dione To a mixture of <strong>[125314-13-8]3-(1-methylindol-3-yl)-4-(3-aminophenyl)-1H-pyrrole-2,5-dione</strong> (0.2 g, 0.6 mmol) and 4-hydroxy-2-butanone (80 mg, 1,5 eq) in dichloromethane (15 mL) was added NaCNBH3 (56 mg, 1.5 eq) and the reaction mixture was stirred at RT for three days. The product 3-(1-methylindol-3-yl)-4- [3-(3-hydroxy-1-methylpropylamnino)phenyl]-1H-pyrrole-2,5-dione separated by preparatory TLC (8.9 mg, 3.6%). LC/MS: M+389. |
Yield | Reaction Conditions | Operation in experiment |
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In N,N-dimethyl-formamide; | EXAMPLE VII 1-(1-Methyl-4-oxo-2-imidazolidinylidene)-3-p-tolylurea To a stirring suspension of <strong>[60-27-5]creatinine</strong> (11.88 g, 0.105 mole) in 100 ml dry DMF, p-tolylisocyante (13.31 g - 0.100 mole) is added dropwise over a period of about 15 minutes with cooling. After stirring for 3.5 hrs., the mixture is poured into about 500 ml iced-water to give white crystals of product which are filtered off and washed with water. Recrystallization of the product from acetone-methanol and then from THF-methanol affords the product, 1-(1-methyl-4-oxo-2-imidazolidinylidene)-3-p-tolyl urea. The crystalline particles are reduced in to finer size by adding a solution of the thus-obtained product in minimal DMF to about 1.1 liters of vigorously stirring water, filtering off and drying the resultant fine crystals in vacuo for 24 hours; m.p. 198-200C dec. |
Yield | Reaction Conditions | Operation in experiment |
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80.1% | With hydrogenchloride; potassium iodide; potassium hydrogencarbonate; In methanol; water; toluene; | EXAMPLE 2 4.87 Parts of 4-(4-chlorophenyl)piperidin-4-ol, 1.91 parts of potassium iodide and 25 parts of deionized water is stirred together and gently warmed under a nitrogen atmosphere. Then, 2.75 parts of potassium bicarbonate and 6.17 parts of 1,1-dimethoxy-1-(4-fluorophenyl)-4-chlorobutane is added and the mixture is heated to reflux. After heating for 4.5 hours, the reaction mixture is allowed to cool to room temperature and 55 parts of toluene is added. The aqueous and organic layers are separated, and the aqueous layer discarded. 5.1 Parts of methanol is added to the organic layer. Then, 2.5 parts of concentrated hydrochloric acid is added with vigorous stirring. The resulting precipitate is cooled to about 25 C., filtered, washed twice with 22 parts by volume portions of a 10:9:1 mixture of acetone-toluene-methanol, and twice with 20 parts by volume portions of a 10:1 mixture of acetone-methanol. After air-drying, the product, 4-[4-(4-chlorophenyl)-4-hydroxypiperidino]-4' -fluorobutyrophenone hydrochloride, melts at about 227-229 C. and is obtained in 80.1% yield. This compound is the hydrochloride salt of the product of Example 1. |
Yield | Reaction Conditions | Operation in experiment |
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34.4% | 4-hydroxy-2-butanone 11 (20g) was stirred for 5h in liquid ammonia at -76-71 C ?under N2; 240 mL of a methanol solution of hydroxylamine O-sulfonic acid (28 gr, 1.1 mol equivalent) ) in MeOH (200 ml) was then slowly added allowing the temperature to increase at 10-15 C and kept under stirring for 4 days. The white precipitate was filtered off, washed witn MeOH (2x 20mL) , the volume of the solution was carefully reduced to 100 mL (care-volatile product) in vacuo at 30 C, the temperature was reduced to 3 C and cooling kept at the same temperature during the addition in 30 minutes of 30 mL triethylamine (TEA, 1 molar equivalent) . Then 28.8 gram of I2 (0.5 molar equivalent) was slowly added until persistence of colour and the solution allowed to reach r.t. and then stirred again for 2h at 15 C. The total volume of the solution was reduced in vacuo at 30 C with great care (in order to avoid losses of volatile product) to 100 mL; this solution was finally diluted with saturated brine (200 mL) and extracted with ethyl ether (2x 200 mL) , dried overnight on MgSO<, its volume reduced first at 10 mL ad r.t. and finally evaporated in vacuum (100 mbar) affording a yellow liquid which was then distilled at 60-62 C (9 mbar) to yield a clear colourless liquid 12 (81g, yield 34.4%). NMR of 12 (CDCI3) : d 3.55 (q, 6.1 Hz, -CH2OH, 2H) , 1.64 (t, 6.1 Hz, -CH2-CH2OH, 2H, ) , 1.38 (brt, 6.1 Hz, - CH2-OH, 1H) , 1.07 (s, Me-azir, 3H) . | |
3% | To cooled liquid ammonia (-78 C, 30 mL) was added 4-hydroxy-2-butanone (5.3 mL, 60.5 mmol). The solution was stirred at -40 C for 4 hours, and then cooled back to -78 C. To the cooled mixture was added dropwise a solution of hydroxylamine-O-sulfonic acid (7.6 g, 67 mmol) in methanol (60 mL). The cooling bath was removed and the reaction mixture was stirred overnight at room temperature. The suspension was filtered and the residue was washed with methanol extensively. The filtrates were combined and concentrated in vacuo to about 100 mL, and then degassed by passing nitrogen through the filtrates for 20 minutes. The solution was cooled in an ice bath and then triethylamine (7.5 mL, 53.8 mmol) was added followed by iodine (5.0 g, 19.7 mmol). After stirring for 1 hour, another batch of iodine (4.0 g, 15.8 mmol) was added. After 5 minutes, the reaction mixture was concentrated in vacuo to about 100 mL, then brine was added. The aqueous solution was extracted three times with diethyl ether. The organic layers were combined, dried over sodium sulfate, filtered and then concentrated in vacuo. Vacuum distillation (90 C, io~2 mbar) provided the title compound as a yellow oil (226 mg, yield 3 %). (1289) NMR (CDC13): delta = 3·53 (t, 2 H), 1.73 (s, 1 H), 1.64 (t, 2 H), 1.07 (s, 3 H). | |
3- (2-azidoethyl) -3-methyl-3H-diazirine (linker IV) was prepared according to Liang, et al. (Angew Chem Int Ed Engl (2017) 56 (10) : 2744-2748) by switching the solvent N, N-dimethylformamide with acetonitrile.1H NMR (500 MHz, Chloroform-d) = 1.05 (s, 3H) , 1.60 (t, 2H, J = 5.4 Hz) , 3.18 (t, 2H, J = 5.4 Hz) . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | Stage #1: 1-Hydroxy-3-butanone With bromine In methanol at -5 - 20℃; Stage #2: With sulfuric acid In methanol at 0 - 20℃; for 25.5h; | 1.a To 1.9L of a methanol solution containing 169 g (1.92 mol) of 4-hydroxy-2-butanone was added dropwise 300 g (1.88 mol) of bromine at -5°C over 30 minutes. After completion of the dropwise addition, the mixture was gradually elevated to room temperature, and stirred for 2 hours. Subsequently, 3.84 L (3.84 mol) of 2N sulfuric acid was added to the mixture at 0°C, and the resulting mixture was stirred at 10°C for 3.5 hours, and further at room temperature for 22 hours. After completion of the reaction, 325 g of sodium chloride was added to the reaction mixture, and the mixture was extracted with 5.4 L of a chloroform:methanol= 2:1 (V/V) mixed solution. Moreover, the aqueous layer was extracted 4 times with 1.7 L of a chloroform:methanol=9:1 (V/V) mixed solution. The combined organic layers were washed with saturated aqueous sodium hydrogen carbonate solution, and then with a saturated aqueous sodium chloride solution, and concentrated under reduced pressure to obtain 215 g (pure content 176 g) of the title compound as a pale brown oily product. (Yield 55%) Mass spectrum (CI, m/z): 167 (M+). 1H-NMR spectrum (CDCl3, δ ppm): 2.14 (t, J=6.4Hz, 1H), 2.93 (t, J=5.5Hz, 2H), 3.89-3.95 (m, 4H). |
55% | With sulfuric acid; bromine In methanol at -5 - 20℃; for 28h; | 1.1-a Example 1 Ethyl 3-oxo-8-[2-(5,6,7,8-tetrahydroimidazo[1,2-a]pyrimidin-2-yl)ethoxy]-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydro-1H-2-benzazepin-4-acetate hydrochloride 1-(a) 1-Bromo-4-hydroxy-2-butanone To 1.9 L of a methanol solution containing 169 g (1.92 mol) of 4-hydroxy-2-butanone was added dropwise 300 g (1.88 mol) of bromine at -5°C over 30 minutes. After completion of the dropwise addition, a temperature of the mixture was gradually raised to room temperature, and the mixture was stirred for 2 hours. Then, 3.84 L (3.84 mol) of 2N sulfuric acid was added to the mixture at 0°C, the mixture was stirred at 10°C for 3.5 hours, and further stirred at room temperature for 22 hours. After completion of the reaction, 325 g of sodium chloride was added to the reaction mixture, and the mixture was extracted with 5.4 L of a chloroform:methanol= 2:1 (V/V) mixed solution. The aqueous layer was further extracted with 1.7 L of a chloroform:methanol=9:1 (V/V) mixed solution four times. The combined organic layers were washed with a saturated aqueous sodium hydrogen carbonate solution, then, with a saturated aqueous sodium chloride solution, concentrated under reduced pressure to obtain 215 g (pure content: 176 g) of the title compound as pale brown oily product. (Yield: 55%) Mass Spectrum (CI, m/z): 167 (M+). 1H-NMR Spectrum (CDCl3, δ ppm): 2.14 (t, J=6.4Hz, 1H), 2.93 (t, J=5.5Hz, 2H), 3.89-3.95 (m, 4H). |
24.6% | With sulfuric acid; bromine In methanol at 0 - 20℃; for 14h; | 66.1 1-bromo-4-hydroxy-but-2-one The 4-hydroxybut-2-one 66a (6.00g, 68.10mmol), was dissolved in 30mL methanol, 0°C dropwise bromine (10.34g, 64.70mmol), stirred for 2 hours at room temperature. 30mL 2N sulfuric acid was added, stirred for 12 hours at room temperature. The reaction solution was added 30mL of water, DCM / MeOH = 10: 1 (V / V) and extracted (30mL × 3), the combined organic phase was washed with water (20mL × 2), washed with saturated sodium chloride solution (20mL × 2), with dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure, purified by silica gel column chromatography with an eluent system C the resulting residue was purified to give 1-bromo-4-hydroxy-but-2-one 66b (2.80g, as a yellow oil ). Yield: 24.6%. |
With bromine In methanol at 0℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 1-Hydroxy-3-butanone With ammonia In methanol at 0℃; for 4h; Inert atmosphere; Stage #2: With hydroxylamine-o-sulphonic acid In methanol Inert atmosphere; | ||
With ammonia; hydroxylamine-o-sulphonic acid In methanol at 0℃; Sealed tube; | [0234] Synthesis of diazirine: To a 100 mL thick wall pressure vessel containing a ketone compound (1 equiv.) in an ice bath was added 7N ammonia in methanol (MeOH) (7 equiv.). After the vessel was sealed, the reaction mixture was stirred at 0 °C for 4 h. Hydroxylamine O-Sulfonic acid (1.15 equiv.) was dissolved in methanol and then added drop-wise into the reaction mixture. After stirring overnight, most ammonia was removed by gently blowing air through the suspension using a glass pipette, and then the white precipitate was filtered off. After solvents were removed under vacuum, the residue was re-dissolved in methanol followed by the addition of triethylamine (1.5 equiv.). Subsequently, the solution was cooled to 0 °C, and iodine was slowly added until the color of iodine persists for 1 min. After 2 h, methanol was evaporated and the reaction mixture was extracted with ether and dried (Na2S04), filtered, and concentrated to yield the crude product, which was used directly for the next reaction without any purification. [0284] 2-(3-Methyl-3H-diazirin-3-yl)ethyl 4-methylbenzenesulfonate (3 ). 2-(3-Methyl- 3H-diazirin-3-yl)ethanol s6 was synthesized as a crade product from 4-hydroxy-2-butanone s5 by following general procedure 1.6. Compound 3w was synthesized as a colorless oil from crude s6 (500.0 mg, 5.0 mmol), TsCl (1.0 g, 5.25 mmol), Et3N (509.6 mg, 5.5 mmol), and DMAP (600.0 mg, 5.0 mmol) in 12% overall yield from s5 by following general procedure 1.1 : 1H MR (400 MHz, CDC13, δΗ) 7.81 (d, J= 7.5 Hz, 2H), 7.38 (d, J= 7.5 Hz, 2H), 3.96 (t, J= 6.2 Hz, 2H), 2.46 (s, 3H), 1.67 (t, J= 6.2 Hz, 2H), 0.99 (s, 3H); 13C NMR (100 MHz, CDC13, δΗ) 145.30, 132.83, 130.15, 128.12, 65.46, 34.29, 23.62, 21.82, 19.89. ESI-MS: 255.1 (M+H+), 277.1 (M+Na+). | |
Stage #1: 1-Hydroxy-3-butanone With ammonia In methanol at 0℃; for 3h; Inert atmosphere; Stage #2: With hydroxylamine-o-sulphonic acid In methanol at 0 - 20℃; for 16h; Inert atmosphere; | 2-(3-Methyl-3H-diazirin-3-yl)ethyl4-methylbenzenesulfonate (21) 4-hydroxy-2-butanone (20, 1.00 g, 11.35 mmol) was pipetted into a dry flask and cooled to 0°C under nitrogen atmosphere. 7N methanolic ammonia (11.2 mL, 79 mmol) was added via syringe, and the solution was allowed to stir at 0°C for 3 hours. A solution of hydroxylamine-O-sulfonic acid (1.476 g, 13.05 mmol) in methanol (9.7 mL) was added dropwise, then was allowed to stir for an additional 16 hours while slowly warming to room temperature. The reaction was filtered through a sintered glass funnel, then transferred to a reaction vessel and re-cooled to 0°C. Triethylamine (1.58 mL,11.35 mmol) was added, then molecular iodine (2.88 g, 11.35 mmol) was added slowly in 10 equal portions until the purple/brown color of iodine persisted in the reaction vessel. The solvent was removed under reduced pressure, and purification of the crude isolate via Kugelrohr distillation (60°C, 1-3 torr) delivered the 2,2-diazirinyl intermediate as a clear oil (304 mg, 27% yield). A portion of this intermediate (300 mg, 3.00 mmol) was dissolved in dry pyridine (6 mL) and cooled to 0°C in an ice bath. To this solution was added p-toluenesulfonyl chloride (628 mg, 3.30 mmol). The reaction mixture was allowed to stir for 24 hours at 0-4°C, then was poured into a mixture of 37%w/v HCl (15 mL) and ice (80 mL). The resulting suspension was extracted 3x with ether, then the pooled organic layers were washed with 1N HCl solution, 1N NaOH solution, water, and brine. The organic extract was dried over MgSO4, vacuum filtered, and concentrated to a clear oil (428 mg, 15% yield over 3 steps) used without further purification. |
With hydroxylamine-o-sulphonic acid In ammonia at -78 - 20℃; for 12h; Sealed tube; liquid NH3; | 3.2.2. Neutral Substrates (1f-j) General procedure: Ketone (2 mmol) was dissolved in liquid NH3 (8 mL) in a sealed tube at -78 °C.Hydroxylamine-O-sulfonic acid (1.1 equiv.) was carefully added at same temperature. After closing thetube, the reaction mixture was stirred at room temperature for 12 h, before it was cooled at -78 °C andsubsequently opened. KOH (2.3 equiv.) was added to liquid NH3 mixture then the tube was sealed.The reaction mixture was stirred at room temperature under air for 2 h. The ammonia was graduallyremoved at room temperature under a fume hood. The residue was partitioned between water (30 mL)and Et2O (30 mL). The aqueous layer was extracted twice with Et2O (30 mL). The combined organiclayer was washed by brine, dried over MgSO4, and evaporated. The residue was subjected to silica-gelcolumn chromatography to afford the diazirinyl products. | |
With ammonia; hydroxylamine-o-sulphonic acid In methanol at -40 - 20℃; Inert atmosphere; | Compound ii A solution of hydroxylamine-O-sulfonic acid (96.27 g, 851 mmol) in dry methanol (200 mL) was added dropwise to a stirred solution of 4-hydroxybutan-2-one (i) (50 g, 567 mmol) in 7M ammonia in methanol (500 mL) at -40°C under a nitrogen atmosphere. The resulting mixture was stirred at 0°C for at least 5 hours, then overnight at 20°C. The mixture was filtered through Celite and the solvent removed under reduced pressure to yield compound (ii) which was used directly in the next step without further purification. ESI-MS m/z = 103.2 [M+H]+. | |
With ammonium hydroxide; hydroxylamine-o-sulphonic acid In methanol at 20℃; for 14h; Cooling; | 23 32.3 ml of 4-hydroxy-2-butanone, 287 ml of methanol and 78 ml of liquid ammonia were added to a flask cooled in a dry ice-isopropanol bath. 25 g of hydroxylamine-O-sulfonic acid in 287 ml of methanol was dripped into this mixture. The mixture was allowed to reach room temperature over 14 hours. The white precipitate was filtered away and the solvent rotavaped off to yield a diaziridine intermediate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With N-ethyl-N,N-diisopropylamine at 150℃; for 1h; Inert atmosphere; Neat (no solvent); | General procedure: Alcohol (1 mmol), p-methoxybenzyl chloride (1.1 mmol) and diisopropylethylamine (2 mmol) were charged in reaction vessel equipped with magnetic stirring bar under nitrogen atmosphere. The mixture was refluxed in 150 °C bath for 2 h. The resulting mixture typically showed two phases. Ethyl acetate (5 mL) and 10% aqueous sodium bisulphate (5 mL) were added to the mixture and the organic phase extracted by three potions of EtOAc. Combined organic layer was dried over magnesium sulfate and the solvent evaporated in vacuo. Further purification was carried out by silica gel column chromatography. |
63% | With N-ethyl-N,N-diisopropylamine In neat (no solvent) at 150℃; for 2h; | |
53% | With N-ethyl-N,N-diisopropylamine at 150℃; for 2h; Inert atmosphere; |
22.2% | With N-ethyl-N,N-diisopropylamine at 150℃; for 2h; | 1-6 Preparation of a compound of formula 14g-1 Preparation Example 1-6: Preparation of a compound of formula (1-29) A mixture of 4-hydroxy butanone (200 g, 2.27 mol) , benzyl bromide (299 mL, 2.49 mol) and DIPEA (800 mL, 4.52 mol) was heated to 150 °C for 2 hours. After completion, the reaction mixture were dissolved in 500 mL of sodium bi sulphate solution, and then extracted with EtOAc (2 x 1 L) . The combined extracts were washed with water (1 L) , brine (1 L) , dried over anhydrous Na2S04, filtered and evaporated The crude residues were purified by column chromatography using (Si02) by eluting EtOAc : petether (6: 94) to afford 4- (benzyloxy) butan-2-one (14g-l) (90 g, 22.2%) as brown color liquid. XU WAR (CDCI3) δ ppm: 7.35-7.25 (5H, m) , 4.51 (2H, s) , 3.72 (2H, t) , 2.72 (2H, t) ; 2.18 (3H, s) . |
With N-ethyl-N,N-diisopropylamine at 150℃; for 2h; Inert atmosphere; | ||
With N-ethyl-N,N-diisopropylamine at 150℃; for 2h; Inert atmosphere; | ||
With N-ethyl-N,N-diisopropylamine at 150℃; for 2h; Inert atmosphere; | 13 Preparation Example 13 (1o) Under the protection of argon, benzyl bromide (1.78mL, 15mmol) was added to a three-necked flask equipped with a stirring bar and a reflux condenser in sequence.4-Hydroxy-2-butanone (881.1mg, 10mmol), N, N-diisopropylethylamine (2.64mL, 16mmol), reaction at 150 for 2h, the reaction was complete by TLC.The reaction was quenched with 1M hydrochloric acid solution, the organic phase was extracted with ethyl acetate, dried over anhydrous sodium sulfate, concentrated, and silica gel column chromatography,Eluent: petroleum ether: ethyl acetate = 10: 1, the product is a colorless liquid, which is directly used in the next reaction. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With (1S)-10-camphorsulfonic acid In tetrahydrofuran at 20℃; for 6h; Reflux; | 4-(p-Methoxybenzyloxy)butan-2-one (2e) To a solution of 4-hydroxybutan-2-one (86.4 μL, 1.00 mmol) and TriBOT-PM (342.7 mg, 0.700 mmol) in THF (3.33 mL), CSA (23.2mg, 0.100 mmol) was added at r.t. The mixture was heated to reflux for 6 h. After cooling to r.t., the mixture was diluted with Et2O (33 mL), washed with H2O (67 mL), 10% K2CO3 (3 × 33 mL), and brine (33 mL). The organic layer was dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (hexane-EtOAc, 19:1 to 9:1) to afford 2e (174.3 mg, 83%) as a clear colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
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87% | With palladium 10% on activated carbon In ethanol at 20℃; for 16h; Inert atmosphere; | 14 14. Preparation of 3-(methylamino)butan-1-ol (Intermediate M2) 4-hydroxylbutan-2-one (3 g, 34 mmol) and methylamine (12.77 g, 68 mmol) were dissolved in ethanol (10 mL), and 10% palladium on carbon (300 mg) was added. The mixture solution reacted at room temperature for 16 hrs. The reaction solution was filtered, and the filtrate was concentrated to obtain 3-(methylamino)butan-1-ol (3 g, yield 87%), which was directly used in the next step. |
70% | With palladium 10% on activated carbon; hydrogen In ethanol at 20℃; for 16h; | 12 12. Preparation of 3-(methylamino)butan-1-ol (intermediate F10-1) 12. Preparation of 3-(methylamino)butan-1-ol (intermediate F10-1) 4-hydroxylbutan-2-one (1 g, 11.36 mmol) was dissolved in ethanol (10 mL), and methylamine solution (1.7 mL, 22.72 mmol) and 10% palladium on carbon (100 mg) were successively added. The resultant solution reacted at room temperature for 16 hrs under a hydrogen atmosphere. The reaction solution was filtered, and the filtrate was concentrated to obtain 3-(methylamino)butan-1-ol (0.8 g, yield 70%), which was directly used in the next step. |
With palladium 10% on activated carbon; hydrogen In ethanol at 20℃; | D4 3-(methylamino)butan-1-ol To a solution of 4-hydroxybutan-2-one (5 ml, 57.9 mmol) in ethanol (100 mL) were added methanamine (8.65 ml, 69.5 mmol, 33% in ethanol) and Pd/C (3.08 g, 2.89 mmol, 10%), and stirred at r.t overnight under hydrogen gas. The reaction mixture was filtered and the filtrate was concentrated to afford the title compound (5.8 g) as a crude product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With hydroxylamine hydrochloride In ethanol at 20℃; for 4h; Cooling with ice; | |
90% | With hydroxylamine hydrochloride; sodium hydroxide In methanol; water at 0 - 5℃; for 1h; | 3.ii Example 3: Process for the preparation of (R)-3-amino-l-butanol (I): Step-ii: Preparation of 4-hydroxy-2-butanone oxime: Hydroxylamine hydrochloride (9.5 g, 0. 136 mol) was added to a solution of 4-hydroxy-2-butanone (10 g, 0. 1 13 mol) in methanol ( 100 ml) at 0-5 °C. The reaction mixture was stirred with continuous pH adjustment to 4.0-6.0 using 40% aqueous sodium hydroxide solution (-15 ml) for about one hour at 0-5 °C. On completion of the reaction by thin layer chromatography, reaction mass was filtered and the cake was washed with methanol (10 ml) at 0-5°C. The filtrate was distilled by rotary evaporator to obtain 4-hydroxy-2-butanone oxime ( 10.5 g, 90%) as a pale yellow syrup. |
With hydroxylamine hydrochloride; sodium carbonate In methanol at 45 - 50℃; for 2h; | 2.1. Racemic 3-Aminobutanol (R&S) (10) To a solution of 4-hydroxy-2-butanone (5) (250.0 g, 2.84 mol) in methanol (2500 mL) at 20-25 °C, hydroxylamine hydrochloride (207.05 g, 2.9792 mol) was added. Afterwards sodium carbonate (180.45 g, 1.7024 mol) was added portionwise to the reaction mixture so as to maintain the temperatureat 25-30 °C. The mixture was then stirred for 2 h by keeping the temperature of about 45-50 °C. After the disappearance of the starting material which was monitored by TLC, the reaction mixture was filtered to remove inorganic salts which were washed with chilled methanol (250 mL). Then the combined filtrate and washed ones were transferred into a suitable vessel, and reduced using hydrogen in the presence of Raney Nickel at about 40-45 °C. The hydrogen pressure during reduction was maintained at 5-6 Kg/cm2. The reaction mass was cooled to 20-25 °C and filtered to remove the catalyst, and the filtrate was concentrated at 40-45 °C. Trimethylamine (25 m L) was added at 25-30 °C and the mixture was stirred by slowly increasing the temperature to about 100 °C. While increasing the temperature, the pressure in the vessel was slowly decreased to reach finally 5 mbar, when a colourless liquid compound (10) (202.0 g,80 %) was obtained. |
With hydroxylamine hydrochloride; sodium hydroxide In ethanol at 5 - 10℃; | 1.1.1-1.1.5 1. Add 4-hydroxy-2-butanone, 95% ethanol, and hydroxylamine hydrochloride to a 500 ml four-necked flask, stir to clear, and cool to 5 degrees in an ice-water bath.2. Add 40% sodium hydroxide solution in the dropping funnel, add lye dropwise when the temperature of the reaction flask drops to 5 degrees, control the temperature of the reaction flask between 5-10 degrees, and add it for 1-2 hours.3. After dripping, keep the temperature at 5-10 degrees and react for 4 hours, filter with suction, and distill the mixture of ethanol and water off the filtrate under reduced pressure at 50 degrees.4. When the distillate is small, add 20 ml of absolute ethanol and steam once (except for water). At this time, some salt will be precipitated. Add 50 ml of absolute ethanol and shake well, remove the salt by suction, and then steam the filtrate to thicken. shape.It was steamed at 50°C to almost no weight loss, and 30 grams of light yellow viscous oil was obtained, with a gas phase purity of 89.7%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With Au-Pd/carbon catalyst; oxygen; In water; at 100℃; under 2250.23 Torr; for 24h; | General procedure: Reactions were carried out using a Radley?s low pressure glass reactor (50 ml). A butanediol in water (20 ml, 0.6 M) and the catalyst(butanediol/metal ratio2000) were added into the reactor,which was then pressurized with oxygen (3 bar). The reaction mixture was heated to 100 C for 24 h under constant stirring(1000 rpm), then cooled to room temperature and analyzed. 1H-NMR spectroscopy was used for product identification; spectrawere acquired over a 16 scan period using a Bruker 400 MHz DPXsystem with a 5 mm auto tune broadband probe. All samples were prepared as dilute solutions in D2O. Carbon mass balances were calculated and were between 96 and 104%. Blank reactions have also been carried out with no oxidation activity detected in the absence of catalyst or with the KB-B carbon support. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 1% platinum on charcoal; oxygen; In water; at 100℃; under 2250.23 Torr; for 24h; | General procedure: Reactions were carried out using a Radley?s low pressure glass reactor (50 ml). A butanediol in water (20 ml, 0.6 M) and the catalyst(butanediol/metal ratio2000) were added into the reactor,which was then pressurized with oxygen (3 bar). The reaction mixture was heated to 100 C for 24 h under constant stirring(1000 rpm), then cooled to room temperature and analyzed. 1H-NMR spectroscopy was used for product identification; spectrawere acquired over a 16 scan period using a Bruker 400 MHz DPXsystem with a 5 mm auto tune broadband probe. All samples were prepared as dilute solutions in D2O. Carbon mass balances were calculated and were between 96 and 104%. Blank reactions have also been carried out with no oxidation activity detected in the absence of catalyst or with the KB-B carbon support. | |
With oxygen; In water; at 100℃; under 2250.23 Torr; for 24h; | General procedure: Reactions were carried out using a Radley?s low pressure glass reactor (50 ml). A butanediol in water (20 ml, 0.6 M) and the catalyst(butanediol/metal ratio2000) were added into the reactor,which was then pressurized with oxygen (3 bar). The reaction mixture was heated to 100 C for 24 h under constant stirring(1000 rpm), then cooled to room temperature and analyzed. 1H-NMR spectroscopy was used for product identification; spectrawere acquired over a 16 scan period using a Bruker 400 MHz DPXsystem with a 5 mm auto tune broadband probe. All samples were prepared as dilute solutions in D2O. Carbon mass balances were calculated and were between 96 and 104%. Blank reactions have also been carried out with no oxidation activity detected in the absence of catalyst or with the KB-B carbon support. | |
10%Spectr.; 42%Spectr.; 47%Spectr. | With oxygen; In water; at 100℃; under 2250.23 Torr; for 24h; | General procedure: (0017) Reactions were carried out using a Radley's low pressure glass reactor (50ml). A butanediol in water (20ml, 0.6M) and the catalyst (butanediol/metal ratio=2000) were added into the reactor, which was then pressurized with oxygen (3bar). The reaction mixture was heated to 100C for 24h under constant stirring (1000rpm), then cooled to room temperature and analyzed. 1H NMR spectroscopy was used for product identification; spectra were acquired over a 16 scan period using a Bruker 400MHz DPX system with a 5mm auto tune broadband probe. All samples were prepared as dilute solutions in D2O. Carbon mass balances were calculated and were between 96 and 104%. Blank reactions have also been carried out with no oxidation activity detected in the absence of catalyst or with the KB-B carbon support. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With but-2-enenitrile; carbonyl bis(hydrido)tris(triphenylphosphine)ruthenium(II); acetic acid; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In toluene at 120℃; for 27h; Inert atmosphere; Reflux; regioselective reaction; | Synthesis of Pyrazoles from 1,3-Diols: General Procedure: To an oven-dried round bottom flaskcontaining a stir bar was added RuH2(CO)(PPh3)3 (0.03 equiv, 0.015 mmol), Xantphos (0.03 equiv, 0.015mmol), diol (1.00 equiv, 0.50 mmol), and hydrazine (1.00 equiv, 0.50 mmol). The flask was fitted with areflux condenser, placed under vacuum for five minutes, and backfilled with N2. The vacuum / backfillprocess was repeated two more times, then toluene (1.00 mL, 0.5 M) was added. Crotonitrile (2.2 equiv,1.1 mmol) and acetic acid (0.15 equiv, 0.075 mmol) were added. The flask was submerged in an oil bathpre-heated to 120 °C and stirred under N2 atmosphere. After 24 h, the flask was cooled to 23 °C. Thesolution was concentrated in vacuo and purified by flash column chromatography using the solventsystem indicated. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With indium (III) iodide In dichloromethane at 20℃; for 2h; | The general procedure for preparation of 2-O-Bz-3, 4, 6-O-tri-O-Bn-β-Dglucopyranose General procedure: To a solution of 2-O-Bz-3, 4, 6-tri-O-Ben-β-D-glucopyranosyl fluoride (56mg, 0.1mmol) in anhydrous CH2Cl2 (2 mL) containing InI3 (5mg, 0.01mmol), alcohol(0.12mmol) was added. The mixture was allowed to stir for 2h at room temperature.The reaction mixture was evaporated under reduced pressure. The resultant residuewas rapidly eluted through chromatograph on silica gel with toluene or hexane inEtOAc to yield the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.45 g | With SEC-BUTYLAMINE; magnesium chloride; In aq. phosphate buffer; dimethyl sulfoxide; at 15℃; for 24h;Enzymatic reaction; | A mixture of 0.9 gm enzyme ECS-ATA-134 and 7.5 ml PLP solution was added to asol uti on of phosphate buffer (15 ml, of example 2), secondary butyl amine (20 ml) andmagnesium chloride (5 ml) followed Li addition of a substrate solution (0.6 gm 4-Hydroxy butanone in S ml Dimethyl sulfoxide). The reaction mixture was stirred at 1Sfor 24 hours. The reaction mixture was extracted with ethyl acetate and the solvent wasremav?ed by distillation to obtain (R)-3-aminobutan-1 -ol. Y ield: 0.45 gm, 100% R-isomer. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With iodine In dimethyl sulfoxide at 20℃; for 8h; Inert atmosphere; | 3 3. 4-((3-Chlorophenyl)-amino)-2-butanone Adding magnetons in sequence in a 25 mL reaction flask,0.1 mmol I2, 1 mmol 4-hydroxy-2-butanone,1 mmol of 3-chloroaniline and 2 mL of dimethyl sulfoxide,The reaction system was reacted in a nitrogen atmosphere at room temperature for 8 h.The reaction solution is extracted with water and organically laminatedAfter that, it was washed three times with saturated brine, dried over anhydrous sodium sulfate, and then evaporated and evaporated.Petroleum ether = 1 : 4) gave 4-((3-chlorophenyl)-amino)-2-butanone as a yellow oil, yield 86% (169.8 mg). |
86% | With iodine In dimethyl sulfoxide at 20℃; for 8h; | General experimental procedure General procedure: A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol 4-hydroxybutan-2-one, 10 mol% I2 (25.4 mg), 2mL DMSO. The resulting mixture was performed at room temperature for 8 h. After reaction was complete, the resulting mixturewas poured into water (20 mL) and extracted with ethyl acetate (3 x10 mL). The combined organic extracts were washed with brine (3 5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting residue was purified by silica gel columnchromatography (ethyl acetate/petroleum ether 1:20-1:4) to afford the desired products. |
85% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 9h; Inert atmosphere; Green chemistry; |
85% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 9h; Inert atmosphere; | 3 3. 4-((3-chlorophenyl) -amino) -2-butanone In a 25mL reaction flask, add magnetons, 0.2mmol TEMPO (2,2,6,6-tetramethylpiperidine oxide), 0.1mmol TBN (tert-butyl nitrite),1 mmol of 4-hydroxy-2-butanone, 1 mmol of 3-chloroaniline and 2 mL of dimethyl sulfoxide. The reaction system was reacted for 9 h at room temperature under a nitrogen atmosphere.The reaction solution was extracted with water. The organic layers were combined and washed three times with saturated brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was subjected to column chromatography (ethyl acetate / petroleum ether = 1: 4) to obtain 4-((3-chlorophenyl) -amino) -2-butanone as a yellow oil. The yield was 85. % (168.0 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With iodine In dimethyl sulfoxide at 20℃; for 8h; Inert atmosphere; | 4 4. 4-((4-Chlorophenyl)amino)-2-butanone Adding magnetons in sequence in a 25 mL reaction flask,0.1 mmol I2, 1 mmol 4-hydroxy-2-butanone,1 mmol 4-chloroaniline and 2 mL dimethyl sulfoxide,The reaction system was reacted in a nitrogen atmosphere at room temperature for 8 h.The reaction solution is extracted with water,The organic layers were combined and washed three times with saturated brine.Drying with anhydrous sodium sulfate, desolvation under reduced pressure, and residue chromatography (ethyl acetate / petroleum ether = 1: 4) to give 4-((4-chlorophenyl)amino)-2-butanone, yellow and a yield of 90% (177.2 mg). |
90% | With iodine In dimethyl sulfoxide at 20℃; for 8h; | General experimental procedure General procedure: A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol 4-hydroxybutan-2-one, 10 mol% I2 (25.4 mg), 2mL DMSO. The resulting mixture was performed at room temperature for 8 h. After reaction was complete, the resulting mixturewas poured into water (20 mL) and extracted with ethyl acetate (3 x10 mL). The combined organic extracts were washed with brine (3 5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting residue was purified by silica gel columnchromatography (ethyl acetate/petroleum ether 1:20-1:4) to afford the desired products. |
79% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 9h; Inert atmosphere; Green chemistry; |
79% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 10h; Inert atmosphere; | 4 4. 4-((4-chlorophenyl) amino) -2-butanone In a 25mL reaction flask, add magnetons, 0.2mmol TEMPO (2,2,6,6-tetramethylpiperidine oxide),0.1mmol TBN (tert-butyl nitrite), 1mmol 4-hydroxy-2-butanone, 1mmol 4-chloroaniline and 2mL dimethylsulfoxide,The reaction system was reacted in a nitrogen atmosphere at room temperature for 10 hours. The reaction solution was extracted with water. The organic layers were combined and washed with saturated brine three times.Dry with anhydrous sodium sulfate, desolvate under reduced pressure, and treat the residue by column chromatography (ethyl acetate / petroleum ether = 1: 4) to obtain 4-((4-chlorophenyl) amino) -2-butanone.Yellow solid, melting point 71-73 ° C, yield 79% (156.1 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 9h; Inert atmosphere; Green chemistry; | |
76% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 11h; Inert atmosphere; | 5 5. 4-((2-Bromophenyl) amino) -2-butanone In a 25mL reaction flask, add magnetons, 0.2mmol TEMPO (2,2,6,6-tetramethylpiperidine oxide), 0.1mmol TBN (tert-butyl nitrite),1mmol of 4-hydroxy-2-butanone, 1mmol of 2-bromoaniline and 2mL of dimethylsulfoxide. The reaction system was reacted for 11h at room temperature under a nitrogen atmosphere. The reaction solution was extracted with water.The organic layers were combined and washed three times with saturated brine, dried over anhydrous sodium sulfate, and desolvated under reduced pressure.The residue was subjected to column chromatography (ethyl acetate / petroleum ether = 1: 4) to obtain 4-((2-bromophenyl) amino) -2-butanone as a yellow oil in a yield of 76% (184.0 mg). |
71% | With iodine In dimethyl sulfoxide at 20℃; for 8h; Inert atmosphere; | 5 5. 4-((2-bromophenyl)amino)-2-butanone Adding magnetons in sequence in a 25 mL reaction flask,0.1 mmol I2, 1 mmol 4-hydroxy-2-butanone,1 mmol of 2-bromoaniline and 2 mL of dimethyl sulfoxide,The reaction system was reacted in a nitrogen atmosphere at room temperature for 8 h.The reaction solution is extracted with water and organically laminatedAfter that, it was washed three times with saturated brine, dried over anhydrous sodium sulfate, and then evaporated and evaporated.Petroleum ether = 1 : 4) gave 4-((2-bromophenyl)amino)-2-butanone as a yellow oil, yield 71% (172.3 mg). |
71% | With iodine In dimethyl sulfoxide at 20℃; for 8h; | General experimental procedure General procedure: A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol 4-hydroxybutan-2-one, 10 mol% I2 (25.4 mg), 2mL DMSO. The resulting mixture was performed at room temperature for 8 h. After reaction was complete, the resulting mixturewas poured into water (20 mL) and extracted with ethyl acetate (3 x10 mL). The combined organic extracts were washed with brine (3 5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting residue was purified by silica gel columnchromatography (ethyl acetate/petroleum ether 1:20-1:4) to afford the desired products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 9h; Inert atmosphere; Green chemistry; | |
79% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 12h; Inert atmosphere; | 6 6. 4-((3-bromophenyl) amino) -2-butanone In a 25mL reaction flask, add magnetons, 0.2mmol TEMPO (2,2,6,6-tetramethylpiperidine oxide), 0.1mmol TBN (tert-butyl nitrite),1 mmol of 4-hydroxy-2-butanone, 1 mmol of 3-bromoaniline and 2 mL of dimethyl sulfoxide. The reaction system was reacted in a nitrogen atmosphere at room temperature for 12 h.The reaction solution was extracted with water. The organic layers were combined and washed three times with saturated brine, and dried over anhydrous sodium sulfate.Desolvate under reduced pressure and treat the residue by column chromatography (ethyl acetate / petroleum ether = 1: 4)4-((3-Bromophenyl) amino) -2-butanone was obtained as a yellow oil in a yield of 79% (191.2 mg). |
75% | With iodine In dimethyl sulfoxide at 20℃; for 8h; Inert atmosphere; | 6 6. 4-((3-Bromophenyl)amino)-2-butanone Adding magnetons in sequence in a 25 mL reaction flask,0.1 mmol I2, 1 mmol 4-hydroxy-2-butanone,1 mmol of 3-bromoaniline and 2 mL of dimethyl sulfoxide,The reaction system was reacted in a nitrogen atmosphere at room temperature for 8 h.The reaction solution is extracted with water and organically laminatedAfter that, it was washed three times with saturated brine, dried over anhydrous sodium sulfate, and then evaporated and evaporated.Petroleum ether = 1 : 4) gave 4-((3-bromophenyl)amino)-2-butanone as a yellow oil, yield 75% (181.8 mg). |
75% | With iodine In dimethyl sulfoxide at 20℃; for 8h; | General experimental procedure General procedure: A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol 4-hydroxybutan-2-one, 10 mol% I2 (25.4 mg), 2mL DMSO. The resulting mixture was performed at room temperature for 8 h. After reaction was complete, the resulting mixturewas poured into water (20 mL) and extracted with ethyl acetate (3 x10 mL). The combined organic extracts were washed with brine (3 5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting residue was purified by silica gel columnchromatography (ethyl acetate/petroleum ether 1:20-1:4) to afford the desired products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With iodine In dimethyl sulfoxide at 20℃; for 8h; Inert atmosphere; | 7 7. 4-((4-Bromophenyl)amino)-2-butanone Adding magnetons in sequence in a 25 mL reaction flask,0.1 mmol I2, 1 mmol 4-hydroxy-2-butanone,1 mmol of 4-bromoaniline and 2 mL of dimethyl sulfoxide,The reaction system was reacted in a nitrogen atmosphere at room temperature for 8 h.The reaction solution is extracted with water and organically laminatedAfter that, it was washed three times with saturated brine, dried over anhydrous sodium sulfate, and then evaporated and evaporated.Petroleum ether = 1 : 4) gave 4-((4-bromophenyl)amino)-2-butanone as a yellow oil, yield 77% (187.3mg). |
77% | With iodine In dimethyl sulfoxide at 20℃; for 8h; | General experimental procedure General procedure: A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol 4-hydroxybutan-2-one, 10 mol% I2 (25.4 mg), 2mL DMSO. The resulting mixture was performed at room temperature for 8 h. After reaction was complete, the resulting mixturewas poured into water (20 mL) and extracted with ethyl acetate (3 x10 mL). The combined organic extracts were washed with brine (3 5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting residue was purified by silica gel columnchromatography (ethyl acetate/petroleum ether 1:20-1:4) to afford the desired products. |
71% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 9h; Inert atmosphere; Green chemistry; |
71% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 9h; Inert atmosphere; | 7 7. 4-((4-bromophenyl) amino) -2-butanone In a 25mL reaction flask, add magnetons, 0.2mmol TEMPO (2,2,6,6-tetramethylpiperidine oxide),0.1mmol TBN (tert-butyl nitrite), 1mmol 4-hydroxy-2-butanone, 1mmol 4-bromoaniline and 2mL dimethylsulfoxide. The reaction system was reacted for 9h at room temperature under nitrogen atmosphere.The reaction solution was extracted with water. The organic layers were combined and washed three times with saturated brine, and dried over anhydrous sodium sulfate.Desolvate under reduced pressure and treat the residue by column chromatography (ethyl acetate / petroleum ether = 1: 4)4-((4-Bromophenyl) amino) -2-butanone was obtained as a yellow oil in a yield of 71% (171.9 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 9h; Inert atmosphere; Green chemistry; | |
81% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 9h; Inert atmosphere; | 11 11. 4- (o-Toluidine) -2-butanone In a 25mL reaction flask, add magnetons, 0.2mmol TEMPO (2,2,6,6-tetramethylpiperidine oxide),0.1mmol TBN (tert-butyl nitrite), 1mmol 4-hydroxy-2-butanone, 1mmol o-toluidine and 2mL dimethyl sulfoxide,The reaction system was reacted in a nitrogen atmosphere at room temperature for 9 hours, and the reaction solution was extracted with water.The organic layers were combined and washed three times with saturated brine, dried over anhydrous sodium sulfate, and desolvated under reduced pressure.Column chromatography of the residue (ethyl acetate / petroleum ether = 1: 4)4- (o-Toluidine) -2-butanone was obtained as a yellow oil in a yield of 81% (143.6 mg). |
72% | With iodine In dimethyl sulfoxide at 20℃; for 8h; Inert atmosphere; | 8 8. 4-(o-toluidine)-2-butanone Adding magnetons in sequence in a 25 mL reaction flask,0.1 mmol I2, 1 mmol 4-hydroxy-2-butanone,1 mmol o-toluidine and 2 mL dimethyl sulfoxide,The reaction system was reacted in a nitrogen atmosphere at room temperature for 8 h.The reaction solution is extracted with water and the organic layer is combined.After washing three times with saturated brine, dried over anhydrous sodium sulfate, and then evaporated to drynessOlefin = 1 : 4) gave 4-(o-toluidine)-2-butanone as a yellow oil, yield 72% (126.9 mg). |
72% | With iodine In dimethyl sulfoxide at 20℃; for 8h; | General experimental procedure General procedure: A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol 4-hydroxybutan-2-one, 10 mol% I2 (25.4 mg), 2mL DMSO. The resulting mixture was performed at room temperature for 8 h. After reaction was complete, the resulting mixturewas poured into water (20 mL) and extracted with ethyl acetate (3 x10 mL). The combined organic extracts were washed with brine (3 5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting residue was purified by silica gel columnchromatography (ethyl acetate/petroleum ether 1:20-1:4) to afford the desired products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 9h; Inert atmosphere; Green chemistry; | |
81% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In 5,5-dimethyl-1,3-cyclohexadiene at 20℃; for 9h; Inert atmosphere; | 12 12. 4- (m-Toluidine) -2-butanone In a 25mL reaction flask, add magnetons, 0.2mmol TEMPO (2,2,6,6-tetramethylpiperidine oxide),0.1mmol TBN (tert-butyl nitrite), 1mmol 4-hydroxy-2-butanone, 1mmol m-toluidine and 2mL xylene,The reaction system was reacted in a nitrogen atmosphere at room temperature for 9 hours. The reaction solution was extracted with water. The organic layers were combined and washed with saturated brine three times.Dry with anhydrous sodium sulfate, desolvate under reduced pressure, and treat the residue by column chromatography (ethyl acetate / petroleum ether = 1: 4)4- (m-Toluidine) -2-butanone was obtained as a yellow oil in a yield of 81% (143.6 mg). |
79% | With iodine In dimethyl sulfoxide at 20℃; for 8h; Inert atmosphere; | 12 12. 4-(m-toluidine)-2-butanone Adding magnetons in sequence in a 25 mL reaction flask,0.1 mmol I2, 1 mmol 4-hydroxy-2-butanone,1 mmol of toluidine and 2 mL of dimethylimine,The reaction system was reacted in a nitrogen atmosphere at room temperature for 8 h.The reaction solution is extracted with water and the organic layer is combined.After washing three times with saturated brine, dried over anhydrous sodium sulfate, and then evaporated to dryness, and the residue was subjected to column chromatography (ethyl acetate / petroleum ether = 1: 4) to give 4-(m-toluidine) Ketone, yellow oil, yield 79% (140.3 mg). |
79% | With iodine In dimethyl sulfoxide at 20℃; for 8h; | General experimental procedure General procedure: A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol 4-hydroxybutan-2-one, 10 mol% I2 (25.4 mg), 2mL DMSO. The resulting mixture was performed at room temperature for 8 h. After reaction was complete, the resulting mixturewas poured into water (20 mL) and extracted with ethyl acetate (3 x10 mL). The combined organic extracts were washed with brine (3 5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting residue was purified by silica gel columnchromatography (ethyl acetate/petroleum ether 1:20-1:4) to afford the desired products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With iodine In dimethyl sulfoxide at 20℃; for 8h; Inert atmosphere; | 13 13. 4-((4-tert-Butylphenyl)amino)-2-butanone Adding magnetons in sequence in a 25 mL reaction flask,0.1 mmol I2, 1 mmol 4-hydroxy-2-butanone,1 mmol of p-tert-butylaniline and 2 mL of dimethyl sulfoxide,The reaction system was reacted in a nitrogen atmosphere at room temperature for 8 h.The reaction solution is extracted with water and the organic layerAfter the combination, it was washed three times with saturated brine, dried over anhydrous sodium sulfate, and then evaporated and evaporated.Ester/petroleum ether = 1 : 4) gave 4-((4-tert-butylphenyl)amino)-2-butanone as a yellow oil, yield: 92% (202.2mg). |
92% | With iodine In dimethyl sulfoxide at 20℃; for 8h; | General experimental procedure General procedure: A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol 4-hydroxybutan-2-one, 10 mol% I2 (25.4 mg), 2mL DMSO. The resulting mixture was performed at room temperature for 8 h. After reaction was complete, the resulting mixturewas poured into water (20 mL) and extracted with ethyl acetate (3 x10 mL). The combined organic extracts were washed with brine (3 5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting residue was purified by silica gel columnchromatography (ethyl acetate/petroleum ether 1:20-1:4) to afford the desired products. |
88% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 9h; Inert atmosphere; Green chemistry; |
88% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In toluene at 20℃; for 10h; Inert atmosphere; | 14 14. 4-((4-tert-butylphenyl) amino) -2-butanone In a 25mL reaction flask, add magnetons, 0.2mmol TEMPO (2,2,6,6-tetramethylpiperidine oxide),0.1mmol TBN (t-butyl nitrite), 1mmol 4-hydroxy-2-butanone, 1mmol p-tert-butylaniline and 2mL toluene,The reaction system was reacted in a nitrogen atmosphere at room temperature for 10 hours. The reaction solution was extracted with water. The organic layers were combined and washed three times with saturated brine.Dry with anhydrous sodium sulfate, desolvate under reduced pressure, and treat the residue by column chromatography (ethyl acetate / petroleum ether = 1: 4)4-((4-tert-butylphenyl) amino) -2-butanone was obtained as a yellow oil in a yield of 88% (193.0 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With iodine In dimethyl sulfoxide at 20℃; for 8h; Inert atmosphere; | 14 14. 4-((2-Methoxyphenyl)amino)-2-butanone Adding magnetons in sequence in a 25 mL reaction flask,0.1 mmol I2, 1 mmol 4-hydroxy-2-butanone,1 mmol of o-aniline and 2 mL of dimethyl sulfoxide,The reaction system was reacted in a nitrogen atmosphere at room temperature for 8 h.The reaction solution is extracted with water and the organic layerAfter the combination, it was washed three times with saturated brine, dried over anhydrous sodium sulfate, and then evaporated and evaporated.Ester/petroleum ether = 1:4) gave 4-((2-methoxyphenyl)amino)-2-butanone as a brown oil, yield 71% (136.7 mg). |
71% | With iodine In dimethyl sulfoxide at 20℃; for 8h; | General experimental procedure General procedure: A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol 4-hydroxybutan-2-one, 10 mol% I2 (25.4 mg), 2mL DMSO. The resulting mixture was performed at room temperature for 8 h. After reaction was complete, the resulting mixturewas poured into water (20 mL) and extracted with ethyl acetate (3 x10 mL). The combined organic extracts were washed with brine (3 5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting residue was purified by silica gel columnchromatography (ethyl acetate/petroleum ether 1:20-1:4) to afford the desired products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 9h; Inert atmosphere; Green chemistry; | |
89% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 8h; Inert atmosphere; | 14 14. 4-((3-methoxyphenyl) amino) -2-butanone In a 25mL reaction flask, add magnetons, 0.2mmol TEMPO (2,2,6,6-tetramethylpiperidine oxide),0.1mmol TBN (tert-butyl nitrite), 1mmol 4-hydroxy-2-butanone, 1mmol m-methoxyaniline and 2mL dimethyl sulfoxide,The reaction system was allowed to react in a nitrogen atmosphere at room temperature for 8 hours. The reaction solution was extracted with water. The organic layers were combined and washed three times with saturated brine.Dry with anhydrous sodium sulfate, desolvate under reduced pressure, and treat the residue by column chromatography (ethyl acetate / petroleum ether = 1: 4)4-((3-methoxyphenyl) amino) -2-butanone was obtained as a yellow oil in a yield of 89% (172.0 mg). |
74% | With iodine In dimethyl sulfoxide at 20℃; for 8h; Inert atmosphere; | 15 15. 4-((3-Methoxyphenyl)amino)-2-butanone Adding magnetons in sequence in a 25 mL reaction flask,0.1 mmol I2, 1 mmol 4-hydroxy-2-butanone,1 mmol of m-methoxyaniline and 2 mL of dimethyl sulfoxide,The reaction system was reacted in a nitrogen atmosphere at room temperature for 8 h.The reaction solution is extracted with water and the organic layerAfter the combination, it was washed three times with saturated brine, dried over anhydrous sodium sulfate, and then evaporated and evaporated.Ester/petroleum = 1 : 4) gave 4-((3-methoxyphenyl)amino)-2-butanone as a yellow oil, yield 74% (143.1 mg). |
74% | With iodine In dimethyl sulfoxide at 20℃; for 8h; | General experimental procedure General procedure: A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol 4-hydroxybutan-2-one, 10 mol% I2 (25.4 mg), 2mL DMSO. The resulting mixture was performed at room temperature for 8 h. After reaction was complete, the resulting mixturewas poured into water (20 mL) and extracted with ethyl acetate (3 x10 mL). The combined organic extracts were washed with brine (3 5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting residue was purified by silica gel columnchromatography (ethyl acetate/petroleum ether 1:20-1:4) to afford the desired products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With iodine In dimethyl sulfoxide at 20℃; for 8h; Inert atmosphere; | 16 16. 4-((4-Nitrophenyl)amino)-2-butanone Adding magnetons in sequence in a 25 mL reaction flask,0.1 mmol I2, 1 mmol 4-hydroxy-2-butanone,1 mmol p-nitroaniline and 2 mL dimethyl sulfoxide,The reaction system was reacted in a nitrogen atmosphere at room temperature for 8 h.The reaction solution is extracted with water and organically laminatedAfter that, it was washed three times with saturated brine, dried over anhydrous sodium sulfate, and then evaporated and evaporated.Petroleum ether = 1:4) gave 4-((4-nitrophenyl)amino)-2-butanone as a yellow solid, yield 82%(117.3 mg). |
43% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 12h; Inert atmosphere; | 15 15. 4-((4-nitrophenyl) amino) -2-butanone In a 25mL reaction flask, add magnetons, 0.2mmol TEMPO (2,2,6,6-tetramethylpiperidine oxide),0.1mmol TBN (tert-butyl nitrite), 1mmol 4-hydroxy-2-butanone, 1mmol p-nitroaniline and 2mL toluene,The reaction system was reacted in a nitrogen atmosphere at room temperature for 12 hours. The reaction solution was extracted with water. The organic layers were combined and washed with saturated brine three times.Dry with anhydrous sodium sulfate, desolvate under reduced pressure, and treat the residue by column chromatography (ethyl acetate / petroleum ether = 1: 4)4-((4-nitrophenyl) amino) -2-butanone was obtained as a yellow solid with a melting point of 89-91 ° C and a yield of 43% (89.5 mg). |
With iodine In dimethyl sulfoxide at 20℃; for 8h; | General experimental procedure General procedure: A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol 4-hydroxybutan-2-one, 10 mol% I2 (25.4 mg), 2mL DMSO. The resulting mixture was performed at room temperature for 8 h. After reaction was complete, the resulting mixturewas poured into water (20 mL) and extracted with ethyl acetate (3 x10 mL). The combined organic extracts were washed with brine (3 5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting residue was purified by silica gel columnchromatography (ethyl acetate/petroleum ether 1:20-1:4) to afford the desired products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With iodine In dimethyl sulfoxide at 20℃; for 24h; | General experimental procedure General procedure: A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol 4-hydroxybutan-2-one, 10 mol% I2 (25.4 mg), 2mL DMSO. The resulting mixture was performed at room temperature for 8 h. After reaction was complete, the resulting mixturewas poured into water (20 mL) and extracted with ethyl acetate (3 x10 mL). The combined organic extracts were washed with brine (3 5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting residue was purified by silica gel columnchromatography (ethyl acetate/petroleum ether 1:20-1:4) to afford the desired products. |
78% | With iodine In dimethyl sulfoxide at 20℃; for 8h; Inert atmosphere; | 17 17. 2-((3-Oxobutyl)amino)benzonitrile Adding magnetons in sequence in a 25 mL reaction flask,0.1 mmol I2, 1 mmol 4-hydroxy-2-butanone,1 mmol of 2-aminobenzonitrile and 2 mL of dimethyl sulfoxide,The reaction system was reacted in a nitrogen atmosphere at room temperature for 8 h.The reaction solution is extracted with water and the organic layerAfter the combination, it was washed three times with saturated brine, dried over anhydrous sodium sulfate, and then evaporated and evaporated.The ester/petroleum ether = 1:4) gave 2-((3-oxobutyl)amino)benzonitrile as a yellow oil, yield 78% (146.7 mg). |
61% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 9h; Inert atmosphere; Green chemistry; |
61% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 10h; Inert atmosphere; | 16 16. 2-((3-oxobutyl) amino) benzonitrile In a 25mL reaction flask, add magnetons, 0.2mmol TEMPO (2,2,6,6-tetramethylpiperidine oxide),0.1mmol TBN (tert-butyl nitrite), 1mmol 4-hydroxy-2-butanone, 1mmol 2-aminobenzonitrile and 2mL dimethylsulfoxide. The reaction system was reacted for 10h at room temperature under nitrogen atmosphere. The reaction solution was extracted with water. The organic layers were combined and washed three times with saturated brine, and dried over anhydrous sodium sulfate.Desolvate under reduced pressure and treat the residue by column chromatography (ethyl acetate / petroleum ether = 1: 4)2-((3-oxobutyl) amino) benzonitrile was obtained as a yellow oil in a yield of 61% (114.8 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With iodine In dimethyl sulfoxide at 20℃; for 24h; | General experimental procedure General procedure: A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol 4-hydroxybutan-2-one, 10 mol% I2 (25.4 mg), 2mL DMSO. The resulting mixture was performed at room temperature for 8 h. After reaction was complete, the resulting mixturewas poured into water (20 mL) and extracted with ethyl acetate (3 x10 mL). The combined organic extracts were washed with brine (3 5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting residue was purified by silica gel columnchromatography (ethyl acetate/petroleum ether 1:20-1:4) to afford the desired products. |
77% | With iodine In dimethyl sulfoxide at 20℃; for 8h; Inert atmosphere; | 18 18. 4-((3-Oxobutyl)amino)benzonitrile Adding magnetons in sequence in a 25 mL reaction flask,0.1 mmol I2, 1 mmol 4-hydroxy-2-butanone,1 mmol of p-aminobenzonitrile and 2 mL of dimethyl sulfoxide,The reaction system was reacted in a nitrogen atmosphere at room temperature for 8 h.The reaction solution is extracted with water and organically laminatedAfter that, it was washed three times with saturated brine, dried over anhydrous sodium sulfate, and then evaporated and evaporated.Petroleum ether = 1 : 4) gave 4-((3-oxobutyl)amino)benzonitrile as a yellow solid, , yield 77%(145.2 mg). |
66% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 9h; Inert atmosphere; Green chemistry; |
66% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In N,N-dimethyl-formamide at 20℃; for 12h; Inert atmosphere; | 17 17. 4-((3-oxobutyl) amino) benzonitrile In a 25mL reaction flask, add magnetons, 0.2mmol TEMPO (2,2,6,6-tetramethylpiperidine oxide),0.1mmol TBN (t-butyl nitrite), 1mmol 4-hydroxy-2-butanone, 1mmol p-aminobenzonitrile and 2mL N, N-dimethylformamideThe reaction system was reacted in a nitrogen atmosphere at room temperature for 12 hours. The reaction solution was extracted with water. The organic layers were combined and washed three times with saturated brine.Dry with anhydrous sodium sulfate, desolvate under reduced pressure, and treat the residue by column chromatography (ethyl acetate / petroleum ether = 1: 4)4-((3-Oxybutyl) amino) benzonitrile was obtained as a yellow solid with a melting point of 91-93 ° C and a yield of 66% (124.2 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With iodine In dimethyl sulfoxide at 20℃; for 24h; | General experimental procedure General procedure: A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol 4-hydroxybutan-2-one, 10 mol% I2 (25.4 mg), 2mL DMSO. The resulting mixture was performed at room temperature for 8 h. After reaction was complete, the resulting mixturewas poured into water (20 mL) and extracted with ethyl acetate (3 x10 mL). The combined organic extracts were washed with brine (3 5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting residue was purified by silica gel columnchromatography (ethyl acetate/petroleum ether 1:20-1:4) to afford the desired products. |
87% | With iodine In dimethyl sulfoxide at 20℃; for 8h; Inert atmosphere; | 19 19. Methyl 4-((3-oxobutyl)amino)benzoate Adding magnetons in sequence in a 25 mL reaction flask,0.1 mmol I2, 1 mmol 4-hydroxy-2-butanone,1 mmol of methyl p-aminobenzoate and 2 mL of dimethyl sulfoxide, the reaction system was reacted in a nitrogen atmosphere at room temperature for 8 h.The reaction solution was extracted with water, and the organic layer was combined and washed three times with saturated brine, dried over anhydrous sodium sulfate, and evaporated and evaporated.Ethyl acetate/petroleum ether = 1 : 4) gave methyl 4-((3-oxobutyl)amino)benzoate as a yellow solid, yield 87% (192.1 mg). |
84% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 9h; Inert atmosphere; Green chemistry; |
84% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 12h; Inert atmosphere; | 18 18.Methyl 4-((3-oxobutyl) amino) benzoate In a 25mL reaction flask, add magnetons, 0.2mmol TEMPO (2,2,6,6-tetramethylpiperidine oxide),0.1mmol TBN (tert-butyl nitrite), 1mmol 4-hydroxy-2-butanone, 1mmol methyl p-aminobenzoate and 2mL dimethyl sulfoxide,The reaction system was reacted in a nitrogen atmosphere at room temperature for 12 hours. The reaction solution was extracted with water. The organic layers were combined and washed three times with saturated brine.Dry with anhydrous sodium sulfate, desolvate under reduced pressure, and treat the residue by column chromatography (ethyl acetate / petroleum ether = 1: 4)Methyl 4-((3-oxobutyl) amino) benzoate was obtained as a yellow solid with a melting point of 108-110 ° C and a yield of 84% (185.6 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With iodine; In dimethyl sulfoxide; at 20℃; for 8h;Inert atmosphere; | Adding magnetons in sequence in a 25 mL reaction flask,0.1 mmol I2, 1 mmol 4-hydroxy-2-butanone,1mmol <strong>[873-38-1]4-chloro-2-bromoaniline</strong> and 2mL dimethyl sulfoxide,The reaction system was reacted in a nitrogen atmosphere at room temperature for 8 h.The reaction solution was extracted with water, and the organic layer was combined and washed three times with saturated brine, dried over anhydrous sodium sulfate, and evaporated and evaporated.Ethyl ester / petroleum ether = 1:4) gave 4-((2-bromo-4-chlorophenyl)amino)-2-butanone as a yellow oil, yield 76% (209.7mg) |
76% | With iodine; In dimethyl sulfoxide; at 20℃; for 8h; | General procedure: A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol 4-hydroxybutan-2-one, 10 mol% I2 (25.4 mg), 2mL DMSO. The resulting mixture was performed at room temperature for 8 h. After reaction was complete, the resulting mixturewas poured into water (20 mL) and extracted with ethyl acetate (3 x10 mL). The combined organic extracts were washed with brine (3 5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting residue was purified by silica gel columnchromatography (ethyl acetate/petroleum ether 1:20-1:4) to afford the desired products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 9h; Inert atmosphere; Green chemistry; | |
88% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In N,N-dimethyl-formamide at 20℃; for 10h; Inert atmosphere; | 20 20. 4-((2-bromo-4-methylphenyl) amino) -2-butanone In a 25mL reaction flask, add magnetons,0.2mmol TEMPO (2,2,6,6-tetramethylpiperidine oxide), 0.1mmol TBN (tert-butyl nitrite),1 mmol of 4-hydroxy-2-butanone, 1 mmol of 4-methyl-2-bromoaniline and 2 mL of N, N-dimethylformamide. The reaction system was reacted at room temperature under a nitrogen atmosphere for 10 hours.The reaction solution was extracted with water. The organic layers were combined and washed three times with saturated brine, and dried over anhydrous sodium sulfate.The solvent was removed under reduced pressure, and the residue was subjected to column chromatography (ethyl acetate / petroleum ether = 1: 4) to obtain 4-((2-bromo-4-methylphenyl) amino) -2-butanone as a colorless oil. The yield was 88% (225.4 mg). |
84% | With iodine In dimethyl sulfoxide at 20℃; for 8h; Inert atmosphere; | 21 21. 4-((2-Bromo-4-methylphenyl)amino)-2-butanone Adding magnetons in sequence in a 25 mL reaction flask,0.1 mmol I2, 1 mmol 4-hydroxy-2-butanone,1 mmol of 4-methyl-2-bromoaniline and 2 mL of dimethyl sulfoxide,The reaction system was reacted in a nitrogen atmosphere at room temperature for 8 h.The reaction solution was extracted with water, and the organic layer was combined and washed three times with saturated brine, dried over anhydrous sodium sulfate, and evaporated and evaporated.Acid ethyl ester / petroleum ether = 1:4) 4-((2-bromo-4-methylphenyl)amino)-2-butanone, colorless oil, yield 84%(215.7 mg). |
84% | With iodine In dimethyl sulfoxide at 20℃; for 8h; | General experimental procedure General procedure: A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol 4-hydroxybutan-2-one, 10 mol% I2 (25.4 mg), 2mL DMSO. The resulting mixture was performed at room temperature for 8 h. After reaction was complete, the resulting mixturewas poured into water (20 mL) and extracted with ethyl acetate (3 x10 mL). The combined organic extracts were washed with brine (3 5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting residue was purified by silica gel columnchromatography (ethyl acetate/petroleum ether 1:20-1:4) to afford the desired products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With iodine In dimethyl sulfoxide at 20℃; for 8h; Inert atmosphere; | 22 22. 4-((2-Bromo-3-methylphenyl)amino)-2-butanone Adding magnetons in sequence in a 25 mL reaction flask,0.1 mmol I2, 1 mmol 4-hydroxy-2-butanone,1mmol 3-methyl-2-bromo-aniline and 2mL dimethyl sulfoxide, the reaction system was reacted in a nitrogen atmosphere at room temperature for 8h.The reaction solution is extracted with water,The organic layer was combined and washed three times with saturated brine, dried over anhydrous sodium sulfate, and evaporated and evaporated.(ethyl acetate / petroleum ether = 1:4) gave 4-((2-bromo-3-methylphenyl)amino)-2-butanone as a yellow oil.(231.0 mg). |
90% | With iodine In dimethyl sulfoxide at 20℃; for 8h; | General experimental procedure General procedure: A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol 4-hydroxybutan-2-one, 10 mol% I2 (25.4 mg), 2mL DMSO. The resulting mixture was performed at room temperature for 8 h. After reaction was complete, the resulting mixturewas poured into water (20 mL) and extracted with ethyl acetate (3 x10 mL). The combined organic extracts were washed with brine (3 5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting residue was purified by silica gel columnchromatography (ethyl acetate/petroleum ether 1:20-1:4) to afford the desired products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 9h; Inert atmosphere; Green chemistry; | |
82% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 10h; Inert atmosphere; | 21 21. 4-((3-chloro-4-fluorophenyl) amino) -2-butanone In a 25mL reaction flask, add magnetons, 0.2mmol TEMPO (2,2,6,6-tetramethylpiperidine oxide),0.1mmol TBN (tert-butyl nitrite), 1mmol 4-hydroxy-2-butanone, 1mmol 3-chloro-4-fluoroaniline and 2mL dimethylsulfoxide,The reaction system was reacted in a nitrogen atmosphere at room temperature for 10 hours. The reaction solution was extracted with water. The organic layers were combined and washed three times with saturated brine.Dry with anhydrous sodium sulfate, desolvate under reduced pressure, and treat the residue by column chromatography (ethyl acetate / petroleum ether = 1: 4)The product 4-((3-chloro-4-fluorophenyl) amino) -2-butanone was obtained as a yellow oil in a yield of 82% (176.8 mg). |
80% | With iodine In dimethyl sulfoxide at 20℃; for 8h; Inert atmosphere; | 23 23. 4-((3-Chloro-4-fluorophenyl)amino)-2-butanone Adding magnetons in sequence in a 25 mL reaction flask,0.1 mmol I2, 1 mmol 4-hydroxy-2-butanone,1 mmol 3-chloro-4-fluoroaniline and 2 mL dimethyl sulfoxide,The reaction was carried out in a nitrogen atmosphere at room temperature for 8 h, and the mixture was extracted with water. The organic layer was combined and washed three times with brine, dried over anhydrous sodium sulfate and evaporated=1: 4) The product 4-((3-chloro-4-fluorophenyl)amino)-2-butanone was obtained as a yellow oil in a yield of 80% (172.7 mg). |
80% | With iodine In dimethyl sulfoxide at 20℃; for 8h; | General experimental procedure General procedure: A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol 4-hydroxybutan-2-one, 10 mol% I2 (25.4 mg), 2mL DMSO. The resulting mixture was performed at room temperature for 8 h. After reaction was complete, the resulting mixturewas poured into water (20 mL) and extracted with ethyl acetate (3 x10 mL). The combined organic extracts were washed with brine (3 5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting residue was purified by silica gel columnchromatography (ethyl acetate/petroleum ether 1:20-1:4) to afford the desired products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With iodine In dimethyl sulfoxide at 20℃; for 8h; Inert atmosphere; | 24 24. 4-((3,4-Dichlorophenyl)amino)-2-butanone Adding magnetons in sequence in a 25 mL reaction flask,0.1 mmol I2, 1 mmol 4-hydroxy-2-butanone,1 mmol of 3,4-dichloroaniline and 2 mL of dimethyl sulfoxide,The reaction system was stirred at room temperature under a nitrogen atmosphere for 8 h.The reaction solution is extracted with water,The organic layer was combined and washed three times with saturated brine, dried over anhydrous sodium sulfate, and evaporated and evaporated.(ethyl acetate / petroleum ether = 1:4) gave 4-((3,4-dichlorophenyl)amino)-2-butanone as a yellow oil, yield 93%(215.5mg) |
93% | With iodine In dimethyl sulfoxide at 20℃; for 8h; | General experimental procedure General procedure: A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol 4-hydroxybutan-2-one, 10 mol% I2 (25.4 mg), 2mL DMSO. The resulting mixture was performed at room temperature for 8 h. After reaction was complete, the resulting mixturewas poured into water (20 mL) and extracted with ethyl acetate (3 x10 mL). The combined organic extracts were washed with brine (3 5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting residue was purified by silica gel columnchromatography (ethyl acetate/petroleum ether 1:20-1:4) to afford the desired products. |
86% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 9h; Inert atmosphere; Green chemistry; |
86% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 9h; Inert atmosphere; | 22 22. 4-((3,4-dichlorophenyl) amino) -2-butanone In a 25mL reaction flask, add magnetons,0.2mmol TEMPO (2,2,6,6-tetramethylpiperidine oxide), 0.1mmol TBN (tert-butyl nitrite),1 mmol of 4-hydroxy-2-butanone, 1 mmol of 3,4-dichloroaniline and 2 mL of dimethyl sulfoxide. The reaction system was stirred under a nitrogen atmosphere at room temperature for 9 hours.The reaction solution was extracted with water. The organic layers were combined and washed three times with saturated brine, and dried over anhydrous sodium sulfate.Desolvate under reduced pressure and treat the residue by column chromatography (ethyl acetate / petroleum ether = 1: 4)4-((3,4-dichlorophenyl) amino) -2-butanone was obtained as a yellow oil in a yield of 86% (198.7 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With iodine; In dimethyl sulfoxide; at 20℃; for 8h;Inert atmosphere; | Adding magnetons in sequence in a 25 mL reaction flask,0.1 mmol I2, 1 mmol 4-hydroxy-2-butanone,1 mmol of <strong>[38762-41-3]2-chloro-4-bromoaniline</strong> and 2 mL of dimethyl sulfoxide,The reaction system was reacted in a nitrogen atmosphere at room temperature for 8 h.The reaction solution is extracted with water, organicAfter the layers were combined, washed three times with saturated brine, dried over anhydrous sodium sulfate, and evaporated and evaporated.Ethyl ester / petroleum ether = 1 : 4) gave 4-((4-bromo-2-chlorophenyl)amino)-2-butanone, yellow oil, yield 85% (235.6mg) |
85% | With iodine; In dimethyl sulfoxide; at 20℃; for 8h; | General procedure: A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol 4-hydroxybutan-2-one, 10 mol% I2 (25.4 mg), 2mL DMSO. The resulting mixture was performed at room temperature for 8 h. After reaction was complete, the resulting mixturewas poured into water (20 mL) and extracted with ethyl acetate (3 x10 mL). The combined organic extracts were washed with brine (3 5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting residue was purified by silica gel columnchromatography (ethyl acetate/petroleum ether 1:20-1:4) to afford the desired products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With iodine In dimethyl sulfoxide at 20℃; for 8h; Inert atmosphere; | 26 26. 4-((3,5-Dimethylphenyl)amino)-2-butanone Adding magnetons in sequence in a 25 mL reaction flask,0.1 mmol I2, 1 mmol 4-hydroxy-2-butanone,1 mmol of 3,5-dimethylaniline and 2 mL of dimethyl sulfoxide,The reaction system was reacted in a nitrogen atmosphere at room temperature for 8 h.The reaction solution is extracted with water, organicAfter the layers were combined, washed three times with saturated brine, dried over anhydrous sodium sulfate, and evaporated and evaporated.Ethyl ester / petroleum ether = 1:4) product 4-((3,5-dimethylphenyl)amino)-2-butanone, colorless oil, yield 86%(165.1 mg). |
86% | With iodine In dimethyl sulfoxide at 20℃; for 8h; | General experimental procedure General procedure: A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol 4-hydroxybutan-2-one, 10 mol% I2 (25.4 mg), 2mL DMSO. The resulting mixture was performed at room temperature for 8 h. After reaction was complete, the resulting mixturewas poured into water (20 mL) and extracted with ethyl acetate (3 x10 mL). The combined organic extracts were washed with brine (3 5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting residue was purified by silica gel columnchromatography (ethyl acetate/petroleum ether 1:20-1:4) to afford the desired products. |
85% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 9h; Inert atmosphere; Green chemistry; |
85% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In N,N-dimethyl-formamide at 20℃; for 7h; Inert atmosphere; | 23 23. 4-((3,5-dimethylphenyl) amino) -2-butanone In a 25mL reaction flask, add magnetons, 0.2mmol TEMPO (2,2,6,6-tetramethylpiperidine oxide),0.1mmol TBN (tert-butyl nitrite), 1mmol 4-hydroxy-2-butanone,1mmol 3,5- dimethylaniline and 2mL N, N- dimethylformamide, the reaction system under a nitrogen atmosphere at room temperature the reaction 7H,The reaction solution was extracted with water. The organic layers were combined and washed three times with saturated brine, and dried over anhydrous sodium sulfate.Desolvate under reduced pressure and treat the residue by column chromatography (ethyl acetate / petroleum ether = 1: 4)The product 4-((3,5-dimethylphenyl) amino) -2-butanone was obtained as a colorless oil in a yield of 85% (162.6 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 9h; Inert atmosphere; Green chemistry; | |
74% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 9h; Inert atmosphere; | 2 2. 4-((2-chlorophenyl) amino) -2-butanone In the reaction flask were successively added 25mL magneton,0.2mmol TEMPO (2,2,6,6-tetramethylpiperidine oxide), 0.1mmol TBN (tert-butyl nitrite),1 mmol of 4-hydroxy-2-butanone, 1 mmol of 2-chloroaniline and 2 mL of dimethyl sulfoxide. The reaction system was reacted for 9 h at room temperature under a nitrogen atmosphere.The reaction solution was extracted with water. The organic layers were combined and washed three times with saturated brine, dried over anhydrous sodium sulfate, and desolvated under reduced pressure.The residue was subjected to column chromatography (ethyl acetate / petroleum ether = 1: 4) to obtain 4-((2-chlorophenyl) amino) -2-butanone as a yellow oil in a yield of 74% (146.2 mg). |
73% | With iodine In dimethyl sulfoxide at 20℃; for 8h; Inert atmosphere; | 2 2. 4-((2-Chlorophenyl)amino)-2-butanone Add magnets, 0.1 mmol I2, 1 mmol 4-hydroxy-2-butanone, 1 mmol 2-chlorogen in sequence in a 25 mL reaction flask.Aniline and 2mL of dimethyl sulfoxide, the reaction system is reacted in a nitrogen atmosphere at room temperature for 8 hours, and the reaction solution is extracted with water and organically laminated.After that, it was washed three times with saturated brine, dried over anhydrous sodium sulfate, and then evaporated and evaporated.Petroleum ether = 1 : 4) gave 4-((2-chlorophenyl)amino)-2-butanone as a yellow oil, yield 73% (144.1 mg). |
73% | With iodine In dimethyl sulfoxide at 20℃; for 8h; | General experimental procedure General procedure: A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol 4-hydroxybutan-2-one, 10 mol% I2 (25.4 mg), 2mL DMSO. The resulting mixture was performed at room temperature for 8 h. After reaction was complete, the resulting mixturewas poured into water (20 mL) and extracted with ethyl acetate (3 x10 mL). The combined organic extracts were washed with brine (3 5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting residue was purified by silica gel columnchromatography (ethyl acetate/petroleum ether 1:20-1:4) to afford the desired products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 12h; Inert atmosphere; | 8 8. 4-((2-fluorophenyl) amino) -2-butanone In a 25mL reaction flask, add magnetons, 0.2mmol TEMPO (2,2,6,6-tetramethylpiperidine oxide), 0.1mmol TBN (tert-butyl nitrite),1 mmol of 4-hydroxy-2-butanone, 1 mmol of 2-fluoroaniline and 2 mL of dimethyl sulfoxide. The reaction system was reacted in a nitrogen atmosphere at room temperature for 12 h.The reaction solution was extracted with water. The organic layers were combined and washed three times with saturated brine, and dried over anhydrous sodium sulfate.Desolvate under reduced pressure and treat the residue by column chromatography (ethyl acetate / petroleum ether = 1: 4)4-((2-fluorophenyl) amino) -2-butanone was obtained as a yellow oil in a yield of 64% (116.0 mg). |
40% | With iodine In dimethyl sulfoxide at 20℃; for 8h; | General experimental procedure General procedure: A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol 4-hydroxybutan-2-one, 10 mol% I2 (25.4 mg), 2mL DMSO. The resulting mixture was performed at room temperature for 8 h. After reaction was complete, the resulting mixturewas poured into water (20 mL) and extracted with ethyl acetate (3 x10 mL). The combined organic extracts were washed with brine (3 5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting residue was purified by silica gel columnchromatography (ethyl acetate/petroleum ether 1:20-1:4) to afford the desired products. |
With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 9h; Inert atmosphere; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 9h; Inert atmosphere; Green chemistry; | |
71% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 12h; Inert atmosphere; | 9 9. 4-((3-fluorophenyl) amino) -2-butanone In a 25mL reaction flask, add magnetons, 0.2mmol TEMPO (2,2,6,6-tetramethylpiperidine oxide), 0.1mmol TBN (tert-butyl nitrite),1 mmol of 4-hydroxy-2-butanone, 1 mmol of 3-fluoroaniline and 2 mL of dimethyl sulfoxide,The reaction system was reacted in a nitrogen atmosphere at room temperature for 12h.The reaction solution was extracted with water. The organic layers were combined and washed three times with saturated brine, and dried over anhydrous sodium sulfate. Desolvate under reduced pressure and treat the residue by column chromatography (ethyl acetate / petroleum ether = 1: 4)4-((3-fluorophenyl) amino) -2-butanone was obtained as a yellow oil in a yield of 71% (128.6 mg). |
50% | With iodine In dimethyl sulfoxide at 20℃; for 8h; | General experimental procedure General procedure: A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol 4-hydroxybutan-2-one, 10 mol% I2 (25.4 mg), 2mL DMSO. The resulting mixture was performed at room temperature for 8 h. After reaction was complete, the resulting mixturewas poured into water (20 mL) and extracted with ethyl acetate (3 x10 mL). The combined organic extracts were washed with brine (3 5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting residue was purified by silica gel columnchromatography (ethyl acetate/petroleum ether 1:20-1:4) to afford the desired products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 9h; Inert atmosphere; Green chemistry; | |
62% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 9h; Inert atmosphere; | 10 10. 4-((4-fluorophenyl) amino) -2-butanone In a 25mL reaction flask, add magnetons, 0.2mmol TEMPO (2,2,6,6-tetramethylpiperidine oxide), 0.1mmol TBN (tert-butyl nitrite),1 mmol of 4-hydroxy-2-butanone, 1 mmol of 4-fluoroaniline and 2 mL of dimethyl sulfoxide. The reaction system was reacted for 9 h at room temperature in a nitrogen atmosphere.The reaction solution was extracted with water. The organic layers were combined and washed three times with saturated brine, and dried over anhydrous sodium sulfate. Desolvate under reduced pressure and treat the residue by column chromatography (ethyl acetate / petroleum ether = 1: 4)4-((4-fluorophenyl) amino) -2-butanone was obtained as a yellow oil with a yield of 62% (112.3 mg). |
44% | With iodine In dimethyl sulfoxide at 20℃; for 8h; | General experimental procedure General procedure: A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol 4-hydroxybutan-2-one, 10 mol% I2 (25.4 mg), 2mL DMSO. The resulting mixture was performed at room temperature for 8 h. After reaction was complete, the resulting mixturewas poured into water (20 mL) and extracted with ethyl acetate (3 x10 mL). The combined organic extracts were washed with brine (3 5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting residue was purified by silica gel columnchromatography (ethyl acetate/petroleum ether 1:20-1:4) to afford the desired products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With iodine In dimethyl sulfoxide at 20℃; for 24h; | General experimental procedure General procedure: A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol 4-hydroxybutan-2-one, 10 mol% I2 (25.4 mg), 2mL DMSO. The resulting mixture was performed at room temperature for 8 h. After reaction was complete, the resulting mixturewas poured into water (20 mL) and extracted with ethyl acetate (3 x10 mL). The combined organic extracts were washed with brine (3 5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting residue was purified by silica gel columnchromatography (ethyl acetate/petroleum ether 1:20-1:4) to afford the desired products. |
39% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 9h; Inert atmosphere; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With iodine In dimethyl sulfoxide at 20℃; for 24h; | General experimental procedure General procedure: A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol 4-hydroxybutan-2-one, 10 mol% I2 (25.4 mg), 2mL DMSO. The resulting mixture was performed at room temperature for 8 h. After reaction was complete, the resulting mixturewas poured into water (20 mL) and extracted with ethyl acetate (3 x10 mL). The combined organic extracts were washed with brine (3 5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting residue was purified by silica gel columnchromatography (ethyl acetate/petroleum ether 1:20-1:4) to afford the desired products. |
41% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 72h; Inert atmosphere; Green chemistry; | |
40% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 12h; Inert atmosphere; | 19 19. 4-((4-trifluoromethylphenyl) amino) -2-butanone In a 25mL reaction flask, add magnetons, 0.2mmol TEMPO (2,2,6,6-tetramethylpiperidine oxide),0.1mmol TBN (tert-butyl nitrite), 1mmol 4-hydroxy-2-butanone, 1mmol p-trifluoromethylaniline and 2mL dimethylsulfoxide,The reaction system was reacted in a nitrogen atmosphere at room temperature for 12 h. The reaction solution was extracted with water. The organic layers were combined and washed three times with saturated brine.Dry with anhydrous sodium sulfate, desolvate under reduced pressure, and treat the residue by column chromatography (ethyl acetate / petroleum ether = 1: 4)4-((4-trifluoromethylphenyl) amino) -2-butanone was obtained as a yellow solid with a melting point of 89-91 ° C and a yield of 40% (92.5 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With iodine; In dimethyl sulfoxide; at 20℃; for 8h; | General procedure: A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol 4-hydroxybutan-2-one, 10 molpercent I2 (25.4 mg), 2mL DMSO. The resulting mixture was performed at room temperature for 8 h. After reaction was complete, the resulting mixturewas poured into water (20 mL) and extracted with ethyl acetate (3 x10 mL). The combined organic extracts were washed with brine (3 5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting residue was purified by silica gel columnchromatography (ethyl acetate/petroleum ether 1:20-1:4) to afford the desired products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With iodine; In dimethyl sulfoxide; at 20℃; for 8h; | General procedure: A 25 mL RBF was subsequently charged with 1.0 mmol aromatic amines, 1.0 mmol 4-hydroxybutan-2-one, 10 mol% I2 (25.4 mg), 2mL DMSO. The resulting mixture was performed at room temperature for 8 h. After reaction was complete, the resulting mixturewas poured into water (20 mL) and extracted with ethyl acetate (3 x10 mL). The combined organic extracts were washed with brine (3 5 mL), then dried over Na2SO4 and concentrated in vacuum. The resulting residue was purified by silica gel columnchromatography (ethyl acetate/petroleum ether 1:20-1:4) to afford the desired products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With magnesium hydroxide; water In methanol at 50℃; for 10h; Sealed tube; | 1.1; 5.1 1. Condensation reaction and catalyst Acetone and paraformaldehyde were weighed in a total of 21 g at 7:3 (molar ratio).Placed in 100mL with PTFE linerStainless steel reactor,20 g of a methanol/water (5:1 by mass) solution containing 0.3 g of Mg(OH) 2 was added, and the mixture was stirred at 50 ° C after sealing.After 10 h, after the end of the reaction, it was extracted with 3×10 mL of dichloromethane, and the organic phase was combined to give a condensation product. The conversion of the trimaldehyde was 93, and the yield of the condensation product was 82%; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 9h; Inert atmosphere; Green chemistry; | |
82% | With tert.-butylnitrite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dimethyl sulfoxide at 20℃; for 9h; Inert atmosphere; | 13 13. 4- (p-toluidine) -2-butanone In a 25mL reaction flask, add magnetons, 0.2mmol TEMPO (2,2,6,6-tetramethylpiperidine oxide), 0.1mmol TBN (tert-butyl nitrite),1mmol 4-hydroxy-2-butanone, 1mmol p-toluidine and 2mL dimethyl sulfoxide,The reaction system was reacted in a nitrogen atmosphere at room temperature for 9h.The reaction solution was extracted with water. The organic layers were combined and washed three times with saturated brine, and dried over anhydrous sodium sulfate.Desolvate under reduced pressure and treat the residue by column chromatography (ethyl acetate / petroleum ether = 1: 4)4- (p-Toluidine) -2-butanone was obtained as a yellow oil in a yield of 82% (145.3 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With acetic acid In ethanol at 90℃; | General Procedure for the Preparation of 14a-b. General procedure: A mixture of 13 (50 mg, 0.11 mmol) and hydroxyacetone (10 μL, 0.15 mmol) or 4-hydroxy-2-butanone (10 μL, 0.15 mmol) in ethanol (8 mL) was stirred at 90 °C for 24h, using acetic acid as a catalyst. The reaction mixture was concentrated under reduced pressure. The residue was purified by recrystallization from ethanol or methanol to afford 14a-b. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | Stage #1: 1-Hydroxy-3-butanone; benzyl bromide With N-ethyl-N,N-diisopropylamine at 150℃; for 2h; Inert atmosphere; Stage #2: With sodium tetrahydroborate In ethanol at 20 - 30℃; for 1h; Stage #3: With carbon tetrabromide; triphenylphosphine In dichloromethane at 20 - 30℃; for 5.5h; Inert atmosphere; Cooling with ice; | 5 Preparation Example 5 Under the protection of argon, add benzyl bromide (1.78mL, 15mmol) and 4-hydroxy-2-butanone (881.1mg, 10mmol) to a three-necked flask equipped with a stir bar and a reflux condenser.N,N-Diisopropylethylamine (2.64mL, 16mmol) was reacted at 150°C for 2h, and the reaction was complete as detected by TLC. The reaction was quenched with 1M hydrochloric acid solution, the organic phase was extracted with ethyl acetate, dried with anhydrous sodium sulfate, concentrated, and silica gel column chromatography, eluent: petroleum ether: ethyl acetate = 10:1 to 5:1, the product was a yellow liquid 1.30g, directly used in the next reaction.Under air, add the above product (891.2mg, 5mmol) and ethanol (10mL) to an egg-shaped bottle equipped with a stir bar. After fully dissolving, add sodium borohydride (227.0mg, 6mmol) to the system in four batches ( Add within 15 minutes), react at room temperature for 1 hour, and TLC detects that the reaction is complete. The saturated ammonium chloride solution was quenched, the organic phase was extracted with dichloromethane, dried over anhydrous sodium sulfate, concentrated, and the crude product was directly used in the next reaction.Under the protection of argon, add the above crude product, carbon tetrabromide (1.81g, 5.45mmol), dichloromethane (25mL) to the reaction flask equipped with a stir bar, after fully dissolving, add to the system under ice bath Slowly add triphenylphosphine (dissolved in 15mL dichloromethane) (1.44g, 5.5mmol), after the addition, return to room temperature and react for 5.5h. TLC detects that the reaction is complete. Quench with saturated sodium bicarbonate solution, extract the organic phase with dichloromethane, dry with anhydrous sodium sulfate, spin dry, silica gel column chromatography, eluent is petroleum ether to petroleum ether: dichloromethane = 15:1,The product was 981.5 mg of yellow liquid, and the total yield of the two steps was 81%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With triethylamine In tetrahydrofuran at 20℃; for 6h; Cooling with ice; | 2.4 Step 4 (0103) To an ice-cooled solution of 4-hydroxybutan-2-one (12a) (0.881 g, 10.0 mmoL) and triethylamine (1.02 g, 10.0 mmoL) in tetrafydrofuran (2.5 mL) was dropwise added a solution of α-bromopropionyl bromide (1.08 g, 5.00 mmoL) in tetrahydrofuran (2.5 mL) for 4 min under nitrogen. The resulting mixture was warmed to room temperature, and stirred at room temperature for 6 h, and then 10 mL of toluene and 10 mL of water were added to the reaction solution, and the resulting mixture was separated into two phases, and extraction from an aqueous layer was performed with 5 mL of toluene 3 times, and the organic layers were combined and dried over anhydrous magnesium sulfate. The desiccant was filtered off, and then the filtrate was concentrated under reduced pressure to obtain 1.10 g of crude product. The resulting product was purified by silica gel column chromatography (n-heptane/ethyl acetate=3/1) to afford 1.01 g of α-bromopropionic acid 3-oxobutyl ester (13a). A slightly yellow liquid, 90% yield (GC purity 99.0%). (0104) 1H-NMR: 1.79 ppm (CH3-CHBr), d, J=6.98 Hz; 2.20 ppm (CH3-CO), s; 2.80 ppm (CH2-CO), td, J=6.29, 2.34 Hz; 4.33 ppm (CHBr), q, J=6.98 Hz; 4.42 ppm (OCH2), td, J=6.35, 1.32 Hz. |
Tags: 590-90-9 synthesis path| 590-90-9 SDS| 590-90-9 COA| 590-90-9 purity| 590-90-9 application| 590-90-9 NMR| 590-90-9 COA| 590-90-9 structure
[ 20618-42-2 ]
2-(Hydroxymethyl)cyclopentanone
Similarity: 0.67
[ 38580-68-6 ]
4-(Hydroxymethyl)cyclohexanone
Similarity: 0.65
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