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CAS No. : | 3112-85-4 | MDL No. : | MFCD00014741 |
Formula : | C7H8O2S | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | JCDWETOKTFWTHA-UHFFFAOYSA-N |
M.W : | 156.20 | Pubchem ID : | 18369 |
Synonyms : |
|
Num. heavy atoms : | 10 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.14 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 39.54 |
TPSA : | 42.52 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.9 cm/s |
Log Po/w (iLOGP) : | 1.26 |
Log Po/w (XLOGP3) : | 0.5 |
Log Po/w (WLOGP) : | 2.17 |
Log Po/w (MLOGP) : | 1.51 |
Log Po/w (SILICOS-IT) : | 1.12 |
Consensus Log Po/w : | 1.31 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.5 |
Solubility : | 4.92 mg/ml ; 0.0315 mol/l |
Class : | Very soluble |
Log S (Ali) : | -0.96 |
Solubility : | 17.0 mg/ml ; 0.109 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -2.69 |
Solubility : | 0.315 mg/ml ; 0.00202 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.63 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87 %Chromat. | With sodium hypochlorite pentahydrate In water; acetonitrile at 23 - 28℃; for 4 h; | General procedure: 0.25 g (2 mmol) of thioanisole as a substrate, 10 mL of acetonitrile and 2 mL of water were placed in a 50 mL three-necked flask.The internal temperature of the flask was 23 ° C.0.79 g (4.8 mmol) of sodium hypochlorite pentahydrate crystals was added thereto at a time and stirred.The internal temperature of the flask rose to 28 ° C. and gradually decreased.GC analysis was carried out 3 hours after the start of the reaction, and 22percent of methyl phenyl sulfoxide,65percent of methyl phenyl sulfone was formed.As a by-product,6percent of chloromethyl phenyl sulfoxide,7percent of chloromethyl phenyl sulfone,A total of 0.8percent of higher order chlorides were observed.0.79 g (4.8 mmol) of sodium hypochlorite pentahydrate crystals was added and stirring was continued for 1 hour.Thioanisole,Methyl phenyl sulfoxide was completely disappeared and 87percent of methyl phenyl sulfone was formed.As impurities,11percent chloromethyl phenyl sulfone,0.5percent dichloromethyl phenyl sulfone,Production of trichloromethyl phenyl sulfone 1.3percent was observed. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65 %Chromat. | With sodium hypochlorite pentahydrate In water; acetonitrile at 23 - 28℃; for 3 h; | General procedure: 0.25 g (2 mmol) of thioanisole as a substrate, 10 mL of acetonitrile and 2 mL of water were placed in a 50 mL three-necked flask.The internal temperature of the flask was 23 ° C.0.79 g (4.8 mmol) of sodium hypochlorite pentahydrate crystals was added thereto at a time and stirred.The internal temperature of the flask rose to 28 ° C. and gradually decreased.GC analysis was carried out 3 hours after the start of the reaction, and 22percent of methyl phenyl sulfoxide,65percent of methyl phenyl sulfone was formed.As a by-product,6percent of chloromethyl phenyl sulfoxide,7percent of chloromethyl phenyl sulfone,A total of 0.8percent of higher order chlorides were observed.0.79 g (4.8 mmol) of sodium hypochlorite pentahydrate crystals was added and stirring was continued for 1 hour.Thioanisole,Methyl phenyl sulfoxide was completely disappeared and 87percent of methyl phenyl sulfone was formed.As impurities,11percent chloromethyl phenyl sulfone,0.5percent dichloromethyl phenyl sulfone,Production of trichloromethyl phenyl sulfone 1.3percent was observed. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With chlorosulfonic acid In chlorosulfonic acid at 90℃; for 18 h; | 3-Methanesulfonylbenzene-1-sulfonyl chloride The intermediate 3-methanesulfonylbenzene-1-sulfonyl chloride was synthesized according to the methods disclosed in Park et al., J. Med. Chem. 51(21):6902-6915 (2008). Specifically, methyl sulfonyl benzene (110 g, 0.7 mol) was heated for 18 hours at 90° C. in chlorosulfonic acid (450 mL, 6.7 mol) after which time the reaction mixture was allowed to cool to a temperature of about 21° C. before slowly being poured onto crushed ice. The resulting slurry was twice extracted into EtOAc (2 L for each extraction). The organic portions were combined and washed with brine (50 mL) before being dried over sodium sulfate, filtered and concentrated under reduced pressure to provide the intermediate sulfonyl chloride as an off white solid (125 g, yield 75percent). 1H NMR (400 MHz, CDCl3) δ ppm 8.61 (1 h, t, J=1.7 Hz), 8.35-8.31 (2H, m), 7.90 (1H, t, J=7.9 Hz), 3.15 (3H, s). |
6.1% | at 90℃; for 18 h; | Methylsulfonylbenzene (5 g, 32 mmol) was placed into chlorosulfonic acid (37 g, 320 mmol), heated at 90 °Cfor 18 h, and cooled to room temperature. The mixture was slowly poured into crushed ice. The resulting suspensionwas extracted with ethyl acetate (2 3 200 mL). The organic layers were separated, combined, washed with saturatedaqueous NaCl solution (50 mL), and dried with sodium sulfate. After suction filtration, the resulting filtrate was distilledunder reduced pressure. The residue was the intermediate 3-methylsulfonylphenyl-1-sulfonyl chloride (50 mg, yield6.1percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | at 75℃; for 5 h; | General procedure: To a solution of NaOH (15percent w/w, 8 mL) cooled to 5 °C, Br2 (0.4 mL, 15 mmol, 3 equiv) was added dropwise while maintaining the temperature of the mixture below 10 °C. Next, the sulfone (5 mmol, 1 equiv) was added in one portion. The resulting mixture was stirred for the given time (Table 1) at 75 °C. The mixture was cooled to room temperature, and the precipitate filtered off, washed with H2O, dried in air, and crystallized from 2-PrOH. See Supplementary data for the characterization of the bromination products obtained |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | Stage #1: With n-butyllithium In tetrahydrofuran; hexane at 0℃; for 0.666667 h; Stage #2: With diethyl chlorophosphate In tetrahydrofuran; hexane for 0.5 h; Stage #3: at -78℃; for 2 h; |
To a solution of (methylsulfonyl)benzene (2.2 g, 13.9 mmol) in THF (38 mL) at 0 was added n-BuLi (2.5 M in hexanes, 12.2 mL, 30.6 mmol) dropwise over 10 minutes. After the mixture was stirred for 30 min, chlorodiethylphosphonate (2.4 mL, 16.7 mmol) was added dropwise to the reaction. After 30 minutes, a solution of oxetan-3-one (1.0 g, 13.9 mmol) in THF (2 mL) was added dropwise to the reaction mixture at -78 . The reaction mixture was stirred at -78 for 2 hours, then diluted with aqueous NH4Cl (100 mL) and extracted with EtOAc (100 mL x 2) . The combined organic layers were concentrated and the residue was purified by silica gel chromatxography column (petroleum ether/EtOAc = 3/1) to give the title compound (2.4 g, 82percent) as a colorless oil. 1H NMR (400 MHz, CDCl3) : δ7.90-7.88 (m, 2H) , 7.68-7.64 (m, 1H) , 7.57 (t, J= 7.6 Hz, 2H) , 6.13-6.11 (m, 1H) , 5.66-5.64 (m, 2H) , 5.30-5.27 (m, 2H). |
75% | Stage #1: With n-butyllithium In tetrahydrofuran; hexane at 0℃; for 0.75 h; Inert atmosphere Stage #2: With diethyl chlorophosphate In tetrahydrofuran; hexane at 0℃; for 0.5 h; Stage #3: at -78℃; for 2 h; |
3-((Phenylsulfonyl)methylene)oxetane To an oven-dried vial was added (methylsulfonyl)benzene (0.570 g, 3.65 mmol) and the vial was evacuated with argon 3 times. The dry THF (17 mL) was added and the reaction was cooled to 0° C. The 2.5 M BuLi in hexanes (3.21 mL, 8.03 mmol) was added dropwise and the reaction began to stir at 0° C. and stirred for 45 minutes. The diethyl chlorophosphate (0.528 mL, 3.65 mmol) was then added at 0° C. and the reaction stirred for 30 minutes. The reaction was then cooled to -78° C. and the oxetan-3-one (0.330 mL, 5.15 mmol) was then added dropwise and the reaction stirred for 2 h. The reaction was then warmed to rt and filtered through a silica plug. The reaction was then concentrated onto silica and purified by MPLC (20 min, 0-40percent EtOAc:hex) to provide pure 3-((phenylsulfonyl)methylene)oxetane (0.579 g, 2.75 mmol, 75percent yield). 1H NMR (400 MHz, CDCl3): δ 7.91-7.87 (m, 2H), 7.69-7.64 (m, 1H), 7.60-7.55 (m, 2H), 6.12 (quintet, J=2.3 Hz, 1H), 5.66-5.63 (m, 2H), 5.30-5.27 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium permanganate In dichloromethane; water monomer for 12h; Ambient temperature; | |
100% | With 3-chloro-benzenecarboperoxoic acid | |
100% | With potassium permanganate; iron(III) chloride In acetone at -25℃; for 0.5h; |
100% | With dihydrogen peroxide; methyltrioxorhenium(VII) In ethanol for 3h; Ambient temperature; | |
100% | With mesoporous silica; magnesium monoperoxyphthalate hexahydrate In dichloromethane for 1h; Heating; | |
100% | With [1,3,5-C6H3(C((CH2)3N(n-Hex)3)3]PW12O24; dihydrogen peroxide In chloroform-d1 at 20℃; for 2h; | |
100% | With [bis(acetoxy)iodo]benzene; glycidyl ether-based polymer-micelle incarcerated ruthenium In water monomer; acetone at 20℃; for 0.5h; | |
100% | With dodeca-tungstophosphoric acid; poly(acrylamide) based ammonium salt; dihydrogen peroxide In N,N-dimethyl-formamide at 50℃; for 4h; | |
100% | With dihydrogen peroxide; niobium (V) ethoxide In methanol at 45℃; for 1h; chemoselective reaction; | |
100% | With tungstic acid sodium salt dihydrate; dihydrogen peroxide In methanol; water monomer at 40℃; | |
100% | With dihydrogen peroxide; titanium(IV) dioxide In acetonitrile at 20℃; for 1.5h; | |
100% | With 1H-imidazole; tetra-n-butylammonium peroxomonosulfate In dichloromethane at 25℃; for 0.0333333h; chemoselective reaction; | |
100% | With sodium (meta)periodate In water monomer; acetonitrile for 0.416667h; Sonication; | |
100% | With H6PMo11AlO40; dihydrogen peroxide; tri-n-octylmethylammonium chloride In water monomer at 70℃; for 0.166667h; | |
100% | With C78H123N3O3*3H(1+)*O40PW12(3-); dihydrogen peroxide In chloroform; water monomer; acetonitrile at 35℃; for 0.0833333h; enantioselective reaction; | |
100% | With [(C18H37)2(CH3)2N]3[SiO4H(WO5)3]; dihydrogen peroxide In ethyl acetate at 59.84℃; for 2h; | |
100% | With C22H28F6FeN4O6S2; hydrogen; dihydrogen peroxide; glacial acetic acid In water monomer; acetonitrile at 25℃; | |
100% | With dihydrogen peroxide In propan-1-ol; water monomer at 25℃; for 5h; | |
100% | With dihydrogen peroxide In dichloromethane at 25℃; for 1h; | |
100% | With sodium (meta)periodate; ruthenium on carbon In water monomer at 20℃; for 2h; | 3 Add 0.01 g of Ru / C catalyst and 235 mg (1.1 mmol) of sodium periodate to the reaction flask, add 3 mL of water, and then add 124 mg (1 mmol) of methylphenyl sulfide I-3 to the reaction flask while stirring. The reaction was performed at room temperature for 2h. The reaction of methylphenyl sulfide was detected by TLC, and the reaction was stopped. The reaction solution was filtered and washed with dichloromethane (10 mL × 2), and the filtrate and the washing solution were combined. It was washed twice with saturated sodium chloride solution, and water was removed with anhydrous sodium sulfate. The solvent was distilled off and dried to obtain high-quality compound II-3, with a yield of 100%. |
100% | With oxygen; sodium trifluoro-methanesulfinate for 24h; Irradiation; | 1 In a 5mL quartz reaction tube, add anisole (0.5mmol), sodium trifluoromethanesulfinate and a solvent in sequence, and the resulting mixture is placed in an oxygen atmosphere and stirred for 24 hours under light irradiation. The thin layer chromatography plate tracks the reaction process. After the reaction is over, cool to room temperature, and analyze the yield of benzyl sulfone by gas mass spectrometry. |
99% | With oxygen In phosphate buffer; <i>tert</i>-butyl alcohol at 55℃; for 8h; | |
99% | With aq. H202 In methanol at 20℃; for 4h; | |
99% | With dihydrogen peroxide In acetonitrile at 20℃; for 0.5h; | |
99% | With dihydrogen peroxide In water monomer; butan-1-ol at 50℃; for 3h; | |
99% | With C4H9N2O9W In methanol; water monomer at 20℃; for 1.16h; chemoselective reaction; | General procedure for oxidation of sulfides to sulfones: To a stirred solution of sulfide (1.25 mmol) in CH3OH/H2O (1:1, 10 mL), the complex MWG (1.17 g, 2.5 mmol) or DWC (1.12 g, 1.25 mmol) or DWG (1.13 g, 1.25 mmol) were added successively maintaining molar ratio of W:substrate at 2:1. After completion of the reaction, the sulfone obtained was isolated, purified, and characterized by methods similar to those described under the procedure for oxidation of sulfide to sulfoxide. |
99% | With dihydrogen peroxide In nitromethane at 20℃; for 2.5h; | |
99% | With dihydrogen peroxide In water monomer; acetonitrile at 20℃; for 2h; Green chemistry; chemoselective reaction; | |
99% | With dihydrogen peroxide In water monomer at 50℃; for 3h; | 4.10. Procedure for the oxidation of thioanisole to give methyl phenyl sulfone A test tube equipped with a magnetic stirring bar was charged with thioanisole (130.3 mg, 1.0 mmol), aqueous 35% H2O2 (247.7 mg, 2.5 mmol), and Ti-IEZ-MWW (9.9 mg). The mixture was stirred at 50°C for 3 h. The conversion and yield were determined by GC analysis of the toluene solution with biphenyl as an internal standard. The yield of methyl phenyl sulfone was>99%, conversion of thioanisole was >99%, and selectivity (yield/conversion) was >99%. |
99% | With dihydrogen peroxide In water monomer at 20℃; for 10h; | |
99% | With dihydrogen peroxide In water monomer at 41.84℃; for 0.0166667h; Autoclave; | |
99.3% | With sodium hypochlorite pentahydrate In water monomer; toluene at 20 - 24.4℃; for 2.5h; | 4 In a 500 mL four-necked flask, 18.63 g (150 mmol, pH 11) of thioanisole was added as a substrate,And 130 mL of toluene,While stirring in a water bath at 20 ° C.,to this,195.7 g (360 mmol) of a solution in which sodium hypochlorite pentahydrate crystals were diluted with water to an effective chlorine concentration of 13% was added at once.The reaction temperature rose to 24.4 ° C after 30 minutes and gradually approached 20 ° C.After 2 hours GC analysis showed that 98.5% of methylphenylsulfone was formed as a product.Saturated sodium sulfite aqueous solution was added to the reaction solution, followed by washing with water (10 mL × 1 time)Ethyl acetate was added to the aqueous phase and the extraction operation was carried out (20 mL × 3 times)Anhydrous magnesium sulfate was added to the organic phase and dried.After drying, the solvent was distilled off to obtain 23.3 g of methylphenylsulfoneOf white crystals (yield 99.3%, GC purity 99.4%). |
99% | With sodium (meta)periodate In dichloromethane; water monomer; acetonitrile at 75℃; for 1h; | |
99% | With dihydrogen peroxide In acetonitrile at 40℃; for 0.333333h; | |
99% | With selenium(IV) dioxide; dihydrogen peroxide In water monomer; ethyl acetate chemoselective reaction; | 3.2. Synthesis of Sulfones 2a-g General procedure: In a 2 mL volumetric ask, ethyl acetate was added to suldes 1a±c,e±g (1.0 mmoL) or sulde1d, (0.5 mmoL) to make up the required volume. (Solution A: 0.5 M (1a-c,e-g). In the case of 1d, theconcentration was optimized at 0.25 M) In a 2 mL volumetric flask, 0.1 mmoL of SeO2 (11 mg) andH2O2 30 wt. % (10 mmoL, 1.025 mL) were poured, and then water was added until the desired volumewas reached. (Solution B: 0.05 M (SeO2) and 5 M (H2O2). In the case of 1d, a dierent concentrationwas optimized at 0.025 M (SeO2) and 2.5 M (H2O2)). |
99% | With dihydrogen peroxide; Cu2H4O40Te2W8(12-)*(x)H2O*12Na(1+) In acetonitrile at 20℃; for 6h; Sealed tube; | |
98% | With anhydrous potassium sulfate; sulfuric acid potassium salt; potassium peroxomonosulfate; wet-montmorillonite In dichloromethane for 2h; Ambient temperature; | |
98% | With nitric acid In acetic anhydride at 0℃; for 6h; | |
98% | With tert.-butylhydroperoxide In water monomer; acetonitrile at 60℃; for 3h; Inert atmosphere; | |
98% | With niobium carbide; dihydrogen peroxide In ethanol; water monomer at 60℃; for 2.75h; chemoselective reaction; | |
98.8% | With dihydrogen peroxide In methanol; dichloromethane; water monomer at 20℃; for 4h; | |
98% | With dihydrogen peroxide In acetonitrile at 20℃; for 1.5h; | |
98% | With O40PW12(3-)*3C14H16NO3S(1+); dihydrogen peroxide In water monomer at 20℃; for 0.333333h; Green chemistry; | Oxidation of liquid sulfides General procedure: To a stirred mixture of the sulfide (5 mmol), and catalyst (0.05 g, 0.25 mol%) in water (10 mL), 30% aq. H2O2 (0.56 mL, 5 mmol) was added in one portion. The slurry was stirred at room temperature for 20 min. The reaction mixture was cooled to 10 °C, and the catalyst was separated by filtration. The corresponding sulfoxide product was extracted with Et2O from the reaction mixture. Evaporation of the solvent afforded the crude product. The crude product was purified by column chromatography on silica gel using EtOAc/hexane as eluent (method (a)). Similar method was utilized to produce sulfones. In this case 2.2 mL of 30% aq. H2O2 (20 mmol) and 0.15 g of catalyst (0.75 mol%) were utilized (method (b)). |
98% | With Ti(η5-C5H4SiMe2OPh7Si7O11-κ2O2)Cl; dihydrogen peroxide In methanol; water monomer at 50℃; for 3h; chemoselective reaction; | |
98% | With oxygen In Bicyclo[4.4.0]decane at 90℃; for 4h; | |
98% | With dihydrogen peroxide In n-heptane; water monomer at 20℃; for 0.25h; | Oxidation of liquid sulfides General procedure: Liquid sulfides were oxidized to the corresponding sulfones by stirring a solution of the sulfide (1 mmol) and the catalyst(0.04 g) in n-heptane (4 mL). A certain amount of H2O2 (30%aq.) was added as the oxidant. The mixture was stirred for aspecified time at room temperature. After completion of thereaction, the catalyst was separated from the reaction mixtureusing an external magnet. The corresponding sulfone productswere extracted from the reaction mixture with Et2O. The solventwas evaporated to generate the crude product. The crudeproduct was purified by column chromatography on silica gelusing hexane/ethyl acetate as the eluent (method a). |
98% | With C68H108N4O4*4H(1+)*Mo8O26(4-); dihydrogen peroxide In water monomer; acetonitrile at 50℃; for 1h; | |
98% | With Octanoic acid; dihydrogen peroxide In acetonitrile at 50℃; for 0.5h; Schlenk technique; Green chemistry; | 2.3 General Procedure for Oxidation of Sulfideto Sulfone Compounds (Table 4) General procedure: An oven-dried Schlenk flask was allowed to cool toroom temperature and charged sequentially with sulfide(1.0 mmol), MeCN (3.0 mL) and caprylic acid (20 mol%).The reaction was then activated by the addition of 30%H2O2 (2.4 equiv.) and stirred at 50 °C for the required timeas given in Table 4. The progress of reaction was monitoredby GC. After completion of the reaction, the reaction to the reaction mixture. Then the product was extractedwith CH2Cl2 (30 mL) and then washed with distilled water(10 mL). The organic extract dried over Na2SO4 and thesolvent removed under reduced pressure. The resultantproduct was purified (if necessary) by column chromatographyusing silica gel (60-120 mesh) with n-hexaneand ethyl acetate as solvent to get the pure product. Thestructure of the product was confirmed by GC-MS, M.P./B.P. and 1H NMR spectroscopic techniques. |
98% | With dihydrogen peroxide In ethanol; water monomer at 60℃; for 0.583333h; | Oxidation of liquid sulfides General procedure: To a stirred mixture of the sulfide (5 mmol), and catalyst(0.036 g) in EtOH (10 mL), 30% aq. H2O2 (1.68 mL, 15 mmol) was added in one portion. The slurry was stirred at room temperature. After completion of the reaction followed by TLC, the catalyst was separated by filtration. Corresponding sulfoxide was extracted with Et2O from the reaction mixture. Evaporation of the solvent afforded the crude product. The crude product was purified by column chromatography on silica gel using EtOAc/hexane as eluent. |
98% | With potassium peroxymonosulfate; diethylamine In water monomer; acetonitrile at 20℃; for 0.0833333h; | Representative procedure for the oxidation of sulfides to sulfones General procedure: To a well-stirred solution of thioether (1 mmol) and diethylamine (0.2 mmol) in acetonitrile (2 mL) was added the solution of Oxone (1.5 mmol) in water(4 mL). Stirring was continued and the reaction was monitored by TLC. Uponcompletion of the reaction, the mixture was diluted with chilled water. In most of the cases, sulfones were obtained as pure solid products. Thus, they were isolated by simple filtration. However, when the resulting sulfone was a liquid,the product was extracted with ethyl acetate. The organic extract was washedwith water, dried over anhydrous sodium sulfate, and the solvent was removed.The resultant residue on filtration through a short column of silica gel afforded pure sulfone. |
98.9% | With dihydrogen peroxide Reflux; | 2 Oxidation of methyl phenyl sulfide in hydrogen peroxide system In a 50 ml flask, 800 mg (6.45 mmol) of methyl phenyl sulfide,20ml ketone reagent, 50mg metal compound, and then 3.31ml of hydrogen peroxide was added dropwise,And refluxed for a certain period of time at a certain temperature. After the reaction,Most of the solvent was removed by rotary evaporator and then diluted with 50 ml of ethyl acetate.After saturated sodium thiosulfate was washed, washed with saturated brine, and then dried over anhydrous MgSO4, filtered, and finally the solvent was distilled off under reduced pressure to give the crude product.The crude product was isolated and purified by silica gel column to give 993.9 mg of white solid compound with a yield of 98.9%. |
98% | With phthalic anhydride; urea hydrogen peroxide addition compound In ethyl acetate at 20℃; Green chemistry; | Procedure B: General procedure: To a solution of sulfide 1 (200 mg, 1-2 mmol, 1 equiv) in EtOAc (5 mL) was added UHP (3 equiv) and phthalic anhydride (3equiv) and the solution was allowed to stir for 12-16 h at r.t. The reaction was quenched with sat. aq Na2SO3 (10 mL) and then diluted withEtOAc (5 mL). The organics were washed with 1 N aq NaOH (2 × 10mL), H2O (10 mL), and brine (10 mL). The organics were dried (Na2-SO4) and concentrated to give the desired, spectroscopically pure sulfoneproduct. |
98% | With dihydrogen peroxide In ethanol; water monomer at 20℃; for 0.5h; Green chemistry; | |
98% | With CuO#Nb2O5; dihydrogen peroxide In water monomer at 35℃; for 2h; Green chemistry; | 12 Example 12 (catalytic oxidation of methylphenyl sulfide to prepare methyl phenyl sulfone): Add 10 wt% aqueous solution of methylphenyl sulfide to the round bottom flask, then add catalyst 10 (addition amount is 8% of the mass of methyl phenyl sulfide aqueous solution), then add H2O2 (addition amount is methyl phenyl group) 400% of the molar amount of thioether), stirred and mixed uniformly, placed in an oil bath, heated to 35 ° C, and reacted for 120 min. After the reaction was completed, a sample was taken for gas phase analysis. The conversion of methylphenyl sulfide was tested to be 100%, and the yield of methylphenylsulfone was 98%. |
98% | With dihydrogen peroxide In water monomer at 80℃; for 3h; Green chemistry; | 2.6. General procedure for catalytic oxidation of sulfides to sulfones General procedure: To a stirred solution of 5 mmol sulfide in 5 mL water, 0.01 mmol of Ti containing catalyst [PATi (2.81 mg) or PMATi (3.77 mg)] was added, followed by addition of 50% H2O2 (1.36 mL, 20 mmol) in a round bottom flask. The Ti: substrate molar ratio was maintained at 1 : 500 and the substrate: H2O2 molar ratio at 1 : 4. The reaction was conducted at 80 °C temperature. The reaction was monitored by thin-layer chromatography (TLC) and GC. After completion of the reaction, the system was allowed to cool to room temperature. The sulfone obtained was then isolated, purified and characterized by following similar procedure as mentioned under above section. |
98% | With dihydrogen peroxide; 3H(1+)*(PW12O40)(3-) In water monomer at 20℃; for 0.5h; | 2.4.2. General procedure for the oxidation of sulfides General procedure: A mixture of the PW12 nanoflower (10 mg) as catalyst, 30% H2O2 aqueous solution(100 mL) and solvent (600 mL) was placed in a 10mL glass bottle. After 5 min, the substrate(1 mmol) was added under stirring. The reaction time was counted after theaddition of sulfide, and then the reaction mixture was stirred at the experiment temperaturefor the appropriate time. The sample was collected from the mixture at timeintervals and then the progress of the reaction was followed by TLC (eluent: n-hexane/EtOAc, 3:1) and stopped when complete conversion of the substrate wasobserved. The catalyst was filtered off at the end of reactions, washed several timeswith ethyl acetate followed by ethanol (45 mL), heated in an oven at 70 °C overnightand then reused using the same reaction conditions. The starting material andproduct are insoluble in water and it was used just as an environment for stirring.Therefore, the reaction mixture was transferred to a separating funnel and the productwas extracted with CH2Cl2 (35 mL). After evaporation of organic layer, the crudeproducts were recrystallized from hot ethanol and the pure products were obtained in94-98% yield. Recovering of the PW12 nanoflower catalyst was carried out in four consecutiveexperiments. |
98% | With dihydrogen peroxide In water monomer at 20℃; for 1.08333h; Green chemistry; chemoselective reaction; | 2.4. General procedure for oxidation of sulfides General procedure: The catalytic protocol for the oxidation of sulfides was as follows:catalyst (0.005 mmol of Nb) [Catalyst 1 (16.7 mg) or Catalyst 2 (13.9mg)] and 5 mmol of the substrate was placed in a 50 mL two-neckedround-bottomed flask. With constant magnetic stirring at room temperature,50% H2O2 (0.68 mL, 10 mmol) was added to the reactionmixture. The molar ratio of Nb:MPS:oxidant was fixed at 1:1000:2000.Thin-layer chromatography (TLC) and GC were used to monitor theprogress of the reaction. As the reaction was completed, the catalyst wasseparated from the mixture by filtering and repeatedly washed withacetone. The unreacted organic substrates, also the products of the reactionwere extracted using diethyl ether and dried with anhydrousNa2SO4 subsequently distilled under reduced pressure to remove theexcess of diethyl ether. Column chromatography was carried out topurify the products where ethyl acetate:hexane (1:9) was used as themobile phase. IR, NMR spectral analysis, and melting point determinationwere mainly applied for the characterization of the obtainedproducts. |
97% | With 4 A molecular sieve; N-Methylmorpholine N-oxide In acetonitrile at 40℃; for 3h; variation of time, further solvents, absence of molecular sieves; further sulfides; | |
97% | With 4 A molecular sieve; N-Methylmorpholine N-oxide In acetonitrile at 40℃; for 3h; | |
97% | With potassium peroxomonosulfate; kaolin In dichloromethane for 4h; Ambient temperature; | |
97% | With phenylphosphonate; dihydrogen peroxide; methyl tri-n-octyl ammonium hydrogen sulfate at 50℃; for 2h; | |
97% | With dihydrogen peroxide; zirconium tetrachloride In methanol at 20℃; for 0.0166667h; | |
97% | With N,N'-dibenzyl-N,N,N',N'-tetramethylethylenediammonium bis(permanganate); glacial acetic acid In acetonitrile at 20℃; for 0.0333333h; | |
97% | With tetra-n-butylammonium peroxomonosulfate In water monomer at 25℃; for 1h; chemoselective reaction; | |
97% | With dihydrogen peroxide In acetonitrile at 20℃; for 1h; Green chemistry; chemoselective reaction; | Synthesis of sulfoxides and sulfones General procedure: To a stirred suspension of the selected sulphide (10 mmol) andthe heterogeneous catalyst 4.2% VMIL(101) (0.1 g,∼2.5 mol%) inmethanol (10 ml), H2O2 (8 mmol) was added in one portion. Theslurry was stirred at room temperature for 20 min. The catalyst wasfiltered off and washed with methanol (10 ml). Ethyl acetate (10 ml)was added and resulting solution was dried with anhydrous sodiumsulphate and evaporated in vacuo to afford the crude product whichwas purified by column chromatography on silica gel (10% EtOAc inhexane) to afford the pure sulfoxide. Similar method was utilizedto produce sulfones. In this case 4 mol% of VMIL(101) in CH3CNwere utilized. |
97% | With C2MoO9(2-)*H2O*2C19H42N(1+); dihydrogen peroxide In water monomer at 20℃; for 0.166667h; chemoselective reaction; | |
97% | With Na2[Nb(O2)3(nic)(H2O)]*H2O; dihydrogen peroxide In water monomer at 20℃; for 1.16667h; chemoselective reaction; | |
97% | With dihydrogen peroxide In acetonitrile at 25℃; for 1.5h; chemoselective reaction; | 2.2 Synthesis of sulfoxides and sulfones General procedure: H2O2 (8 mmol) was added in one portion to a stirred suspension of the selected sulfide (1 mmol) and VNaTNT heterogeneous catalyst in water (5 mL). The resulting slurry was then stirred at room temperature for 30 min. Ethanol (10 mL) was used to filter off and wash the catalyst. Ethyl acetate (5 mL) was added and the resulting solution was dried on anhydrous sodium sulfate and the solvents removed in vacuo to afford the crude product. This was then purified by column chromatography using silica gel and 10% EtOAc in hexane as the eluent to afford pure sulfoxide. Sulfones were synthesized by a similar method using 5 mol% of VNaTNT in CH3CN. |
97% | With tert.-butylhydroperoxide; [MoO3(2,2′-bipyridine)]n In decane; dichloromethane at 40℃; for 16h; | 2.3 General procedure for sulfide oxidation General procedure: To a 0.5 M solution of sulfide in CH2Cl2 was added TBHP (5.5 M solution in decane, 1.5 or 3 mol equiv.) and the catalyst (3 mol%). The suspension was stirred at 20°C or 40°C for 1-20 h and then filtered through a short pad of Celite. The solution was concentrated under reduced pressure and the crude residue purified by flash column chromatography (silica gel). |
97% | With C20H18ClNbO2; dihydrogen peroxide In acetonitrile at 70℃; for 4h; Inert atmosphere; | |
97% | With water monomer; 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo-[2.2.2]octane bis(tetrafluoroborate) In acetonitrile at 20℃; for 6h; | Sulfones 3; General Procedure General procedure: In air, to a vial containing a magnetic stirring bar were added 1 (0.5 mmol), MeCN (2 mL), H2O (18 L, 1.0 mmol), and Selectfluor (354 mg,1.0 mmol). Then the contents of the vial were stirred in air at rt for the indicated time (Table 2). The reaction could be monitored by TLC analysis. The reaction mixture was concentrated under reduced pressureand subjected to column chromatography using PE/EtOAc (from 5:1 to 2:1) as eluent to afford the desired products 3. |
96% | With 2-phenylselenobenzoic acid; dihydrogen peroxide In methanol for 120h; | |
96% | With potassium peroxomonosulfate; aluminium chloride anhydrous for 0.5h; Heating; | |
96% | With chromium(VI) oxide; orthoperiodic acid In acetonitrile at 20℃; for 0.2h; | |
96% | With dihydrogen peroxide In methanol; water monomer at 60℃; for 12h; | |
96% | With [bis(acetoxy)iodo]benzene; 4 A molecular sieve; polymer intercalated (RuCl2(PPh3)3) In acetone at 20℃; for 0.25h; | |
96% | With aluminium chloride anhydrous; 3-carboxypyridinium chlorochromate In acetonitrile for 0.00833333h; microwave irradiation; | |
96% | With 1H-imidazole; manganese(II) tetraphenylporphyrinate; tetra-n-butylammonium peroxomonosulfate In dichloromethane at 20℃; for 0.0166667h; | |
96% | With sodium chlorine monoxide In water monomer; toluene at 20℃; for 1h; | 6 (Example 6) (Methylthio)benzene (1.00 g, 8.05 mmol) and cyanuric acid (104 mg, 0.81 mmol) were mixed with toluene (20 mL). 10% aqueous solution of sodium hypochlorite (13.8 g, 18.5 mmol) was added to the mixture at room temperature, and the obtained mixture was stirred for 1 hour. After that, sodium sulfite (507 mg, 4.03 mmol) and water (10 mL) were added to the reaction mixture, and it was extracted with ethyl acetate (10 mL). An aqueous layer was extracted with ethyl acetate (10 mL), and a combined organic layer was washed with saturated saline (10 mL). The organic layer was concentrated under reduced pressure, and the obtained residue was subjected to purification by means of a silica gel column to obtain (methylsulfonyl)benzene (1.21 g, yield: 96%). 1H-NMR (300MHz, CDCl3) δ 3.06 (3H, s), 7.54-7.68 (3H, m), 7.93-7.98 (2H, m) |
96% | With sodium chlorine monoxide; water monomer; isocyanuric acid In toluene at 20℃; for 1h; Inert atmosphere; | |
96% | With dihydrogen peroxide In 1,2-dichloro-ethane for 0.25h; Reflux; | |
96% | With methyltri-n-octylammonium dihydrogenophosphate; tungstic acid sodium salt dihydrate; dihydrogen peroxide In water monomer at 20 - 60℃; for 2h; | |
96% | With 1-butyl-3-methylimidazolium perrhenate; dihydrogen peroxide; 1-n-butyl-3-methylimidazolium tetrafluoroborate In water monomer at 60℃; for 1.5h; Schlenk technique; Inert atmosphere; Green chemistry; | 2.3 Catalytic oxidation of sulfides General procedure: To a stirred solution of sulfide (10mmol) and [C4mim][ReO4] (0.1955g, 5 mol%) in [C4mim][BF4] (2mL), an aqueous solution of hydrogen peroxide (35% in water) (3.5mL, 40mmol) is added in 2-3 portions at 60°C. The progress of the reaction is followed by TLC. The reaction mixture is extracted with diethyl ether (5×10mL) and the extract is dried over anhydrous MgSO4. The yield and selectivity of methyl phenyl sulfone are calculated from calibration curves (r2>0.999) recorded using 3-methylanisole and 1,4-diacetylbenzene as internal standard. The crude product is obtained by rolling evaporation and purified by column chromatography separation (silica gel using hexane/ethyl acetate 90:10 v/v). The RTIL phase is diluted with CH2Cl2 and then treated with MnO2 to destroy the excess peroxide. The obtained liquid is first dried over anhydrous MgSO4 and then for 4h in vacuo at 50°C to remove CH2Cl2. Fresh substrate and hydrogen peroxide are then added for a new reaction cycle. All products are characterized by melting point, 1H NMR, 13C NMR and IR spectroscopy (see Supporting information). |
96% | With oxygen at 100℃; for 20h; Schlenk technique; chemoselective reaction; | |
95% | With potassium peroxomonosulfate In methanol; water monomer at 0 - 20℃; for 4h; | |
95% | With formic acid; dihydrogen peroxide; urea for 2h; Ambient temperature; | |
95% | With potassium permanganate In acetonitrile at 20℃; for 4h; | |
95% | With dihydrogen peroxide In acetonitrile at 20℃; for 0.75h; | |
95% | With aluminium chloride anhydrous; butyltriphenylphosphonium dichromate In acetonitrile for 0.0166667h; microwave irradiation; | |
95% | With N-methylpyrrolidine-2-one hydrotribromide; dihydrogen peroxide In water monomer; acetonitrile at 80℃; for 0.1h; | |
95% | With borax; dihydrogen peroxide; sodium hydroxide In methanol; water monomer at 20℃; for 2.5h; chemoselective reaction; | |
95% | With copper(II) phthalocyanine; tetra-n-butylammonium peroxomonosulfate In water monomer at 25℃; for 1h; | |
95% | With dihydrogen peroxide In acetonitrile at 20℃; for 0.583333h; chemoselective reaction; | 2.4. Synthesis of sulfoxides and sulfones General procedure: To a stirred suspension of the selected sulfide (1 mmol) and the heterogeneous catalyst PW12(at)Al-MCF (3 mol%) in methanol (5 ml), H2O2 (8 mmol) was added in one portion. The slurry was stirred at room temperature for 20 min. The catalyst was filtered off and washed with methanol (5 ml). Ethyl acetate (5 ml) was added and resulting solution was dried with anhydrous sodium sulfate and evaporated in vacuo to afford the crude product which was purified by column chromatography on silica gel (10% EtOAc in hexane) to afford the pure sulfoxide. |
95% | With nonanebis(peroxoic acid) In water monomer at 50 - 55℃; for 0.416667h; | |
95% | Stage #1: methyl-phenyl-thioether With 4,4'-di-tert-butylbiphenyl; lithium In tetrahydrofuran at -78℃; Inert atmosphere; Stage #2: With potassium peroxomonosulfate In methanol; water monomer at 20℃; Inert atmosphere; | |
95% | With dihydrogen peroxide In ethanol; hexane; water monomer at 60℃; for 0.166667h; | 2.5.1. Oxidation of liquid sulfides to sulfoxides General procedure: A mixture of 0.01 g of the catalyst and 30% H2O2 (4 mmol)aq. was added to a solution of the sulfide (1 mmol) in a mixedsolvent of EtOH and hexane (1:1; 2 mL), and the resulting mixturewas stirred at room temperature. At the end of the reaction,the catalyst was separated using an external magneticfield. The corresponding sulfoxide was then extracted withEtOH from the reaction mixture (Method a, Table 1). |
95% | With diethylene glycol dibutyl ether; oxygen at 110℃; for 20h; Green chemistry; | |
95% | With diethylene glycol dibutyl ether; oxygen at 110℃; for 20h; | |
94% | With sodium perborate In methanol; sodium hydroxide | |
94% | With sodium perborate In glacial acetic acid at 50 - 60℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 100% 2: 24% | With C24H32N4O10V2*2CH4O; dihydrogen peroxide In acetonitrile at 60℃; for 0.5h; | 3.3. Catalytic reactivity of complexes General procedure: The catalytic oxidation of thioanisole (Scheme 2) as a representativesubstrate of sulfides was studied in the presence ofcomplexes 1 and 2 as catalyst and aqueous hydrogen peroxide asgreen oxidant. The results of control experiments revealed that thepresence of both catalyst and oxidant (H2O2) is essential for theoxidation. The control reactions were carried out with 1 mmol ofthioanisole in CH3CN and in the presence of 2 mmol catalyst or2 mmol H2O2 at room temperature. The oxidation of thioanisole inthe absence of H2O2 does not occur and in the absence of catalystthe oxidation proceeds only up to 6% after 1 h. Thioanisole was converted to the corresponding sulfoxide with100% selectivity by complexes 1 and 2 at room temperature. Resultsof the studies are summarized in Table 4. In order to achieve themaximum oxidation of thioanisole, some important parameterslike the oxidant concentration (moles of oxidant per moles of thioanisole),solvent and temperature of the reaction were investigatedin the presence of complex 1. The effects of oxidantconcentration on the oxidation of thioanisole are illustrated in Table 4 (entries 3e5). Different oxidant:thioanisole molar ratios(1:1, 2:1 and 3:1) were considered while the ratio of thioanisole(1.0 mmol) to catalyst (2 mmol) in 3mL of acetonitrile was constant.The reactions were carried out at room temperature. The conversionof thioanisole increased with increasing the amount ofhydrogen peroxide from 1:1 to 3:1. The maximum conversion wasobtained when H2O2:thioanisole mole ratio was 3:1 but selectivitytowards sulfoxide decreased in this case which can be attributed toover-oxidation of sulfoxide to sulfone in the presence of excessoxidant. The reaction was selective towards sulfoxide when theH2O2/thioanisole mole ratio was 2:1. Therefore, the H2O2:thioanisolemole ratio of 2:1 is selected as the best value of oxidant/substrate ratios for oxidation of thioanisole. |
1: 98% 2: 2% | With cerium(III) sulphate; barium bromate In lithium hydroxide monohydrate; acetonitrile at 20℃; for 23.3333h; Title compound not separated from byproducts; | |
1: 98% 2: 2% | With sodium hypochlorite pentahydrate In lithium hydroxide monohydrate; acetonitrile at 20℃; for 0.3h; Green chemistry; | Representative Procedure for the Synthesis of Sulfoxides through the Reaction of Sulfides with NaOCl·5H2O: To a solution of thioanisole (1a; 248 mg, 2.0 mmol) in MeCN (10 mL) and H2O (2 mL), NaOCl·5H2O (362 mg, 2.2 mmol) was added and the mixture was stirred at r.t. for 18 min. H2O (20 mL) and CHCl3 (15mL) were added, the organic layer was separated, and the aqueous phase was extracted with CHCl3 (3 × 15 mL). The extracts were dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatography (n-hexane-EtOAc, 1:2 v/v) to provide methyl phenyl sulfoxide (2a; 275 mg, 98%) as colorless crystals. Methyl phenyl sulfone (3a; 6 mg, 2%) was also obtained as colorless crystals. |
1: 2% 2: 97% | With dihydrogen peroxide; methylrhenium(VII) trioxide In ethanol for 1h; Ambient temperature; | |
1: 97% 2: 3% | With dihydrogen peroxide at 50℃; for 4h; | |
1: 97% 2: 20% | With dioxofluoro(bis-dimethylpyrazole) vanadium(V); dihydrogen peroxide In lithium hydroxide monohydrate; acetonitrile at 0 - 27℃; for 2.5h; Cooling with ice; | Typical procedure for the oxidation of methyl phenyl sulfide General procedure: methyl phenyl sulfide (0.248 g, 2 mmol) in acetonitrile (2 ml) solvent was reacted with VO2F(dmpz)2 (0.0059 g, 0.02 mmol) and H2O2 (30% aqueous solution, 25 μL, 2.2 mmol) under stirring at ice bath temperature for 5 h and monitored by TLC. On completion of the reaction, acetonitrile was removed under reduced pressure and 1 ml of water was added. The product was extracted with ethyl acetate, dried over anhydrous MgSO4, and evaporated to dryness, while the aqueous layer was retained for recovery of the catalyst. In order to remove any traces of VO2F(dmpz)2, the product was transferred to silica gel (60-120 mesh) column and eluted with ethyl acetate: hexane (1:7). The aqueous layer is concentrated and reused. The spectral data of some representative compounds are given below.Methyl phenyl sulfoxide (entry 1): IR(neat): 1032 cm-1; 1H NMR (400 MHz, CDCl3): δ 2.74 (s, 3H), 7.51-7.53(m, 3H), 7.64-7.66 (m, 2H) ppm; MS: m/z 157 (M+); |
1: 94% 2: 3% | With tert.-butylhydroperoxide; mesoporous silica In dichloromethane at 25℃; for 0.25h; | |
1: 94% 2: 6% | With dihydrogen peroxide In ethyl acetate at 25℃; for 3h; | |
1: 94% 2: 6% | With Ce(acetylacetonate)3; oxygen In methanol; acetonitrile at 30℃; for 28h; Irradiation; Schlenk technique; | |
1: 93% 2: 5.4 % Chromat. | With aluminum(III) oxide; sodium hypochlorite In propan-2-one at 20℃; for 0.333333h; various solvents and metal catalysts; | |
1: 5.4 % Chromat. 2: 93% | With aluminum(III) oxide; sodium hypochlorite In propan-2-one at 20℃; for 0.333333h; | |
1: 93% 2: 1 % Spectr. | With chloro-trimethyl-silane In acetonitrile at -15℃; for 5h; | |
93% | With dihydrogen peroxide In methanol; lithium hydroxide monohydrate at 25℃; for 4h; | |
1: 93% 2: 3% | With dihydrogen peroxide In methanol; lithium hydroxide monohydrate at 28℃; for 9h; | |
93% | With Ti(OCH(CH3)2)N(CH2C6H3C(CH3)3O)3; dihydrogen peroxide In methanol; lithium hydroxide monohydrate at 28℃; chemoselective reaction; | |
92% | With aq. H202 In methanol at 20℃; for 1.5h; | |
92% | With dihydrogen peroxide In methanol at 25℃; for 1h; | |
92.8% | With nano-sized mesoporous sodium iron hydroxyphosphate supported gold; dihydrogen peroxide In methanol; lithium hydroxide monohydrate at 60℃; for 0.166667h; Green chemistry; | |
1: 2% 2: 91% | With potassium peroxomonosulfate | |
1: 91% 2: 3 %Chromat. | With dihydrogen peroxide In lithium hydroxide monohydrate; acetonitrile at 19.84℃; for 4h; | |
1: 91% 2: 8% | With [bis(acetoxy)iodo]benzene; toluene-4-sulfonic acid In lithium hydroxide monohydrate at 80℃; for 12h; | General Procedure for the Selective Oxidation of Sulfides General procedure: To a 25 mL glass tube, sulfide (0.2 mmol), PhI(OAc)2 (0.22mmol or 0.42 mmol), p-toluenesulfonicacid (3.4 mg, 0.02 mmol), H2O (1.5 mL) were added and the mixture wasstirred at room temperature or 80 oC for desired time. The mixture was cooled to roomtemperature and extracted by saturated NaHCO3(5 mL), ethyl acetate (25 mL × 4). After dryingwith anhydrous Na2SO4, the organic residue was analysedby GC and then purified by column chromatographyon silica gel (200-300 mesh) with ethyl acetate/petroleum ether to afford thedesired product. |
1: 90% 2: 10% | With tert.-butylhydroperoxide; [Mo2(O)4[2,2'-(1,3-phenylene)bis(4,5-dihydrooxazole-4,2-diyl)]dimethanol}(acac)2] In 1,2-dichloro-ethane for 0.5h; Reflux; | 2.4. General procedure for oxidation of sulfides with TBHP catalyzed by Mo BOX complex General procedure: In a 25 mL round-bottom flask equipped with a magnetic stirring bar, a solution of sulfide (1 mmol), catalyst (6 mg, 0.008 mmol, 0.016 mmol Mo) in 1,2-dichloroethane (4 mL) was prepared. TBHP (2 mmol) was added to this solution and the reaction mixture was stirred under reflux conditions. The reaction progress was monitoredby TLC. After the reaction was completed, the isolation and purification of the products were done as described above. |
1: 89% 2: 6 %Chromat. | With iron(II) acetylacetonate; oxygen at 100℃; for 2h; Autoclave; chemoselective reaction; | |
1: 89% 2: 7% | With Oxone; lithium hydroxide monohydrate In ethanol at 60℃; for 2h; chemoselective reaction; | |
1: 89% 2: 10% | With [bis(acetoxy)iodo]benzene; toluene-4-sulfonic acid In lithium hydroxide monohydrate at 20℃; for 5h; | |
89% | With immobilised lipase B from Candida antarctica; urea hydrogen peroxide addition compound; ethyl acetate at 37℃; for 2h; Enzymatic reaction; chemoselective reaction; | |
1: 88% 2: 11% | With 12-molybdophosphoric acid; dihydrogen peroxide; tri-n-octylmethylammonium chloride In lithium hydroxide monohydrate at 20℃; for 1h; | |
1: 86% 2: 14% | With [5,10,15,20-tetrakis(2,3,4,5,6-pentafluorophenyl)porphyrinato]platinum(II); iodosylbenzene In dichloromethane at 20℃; for 0.5h; | |
85% | With iodine; mercuric (II) oxide In dichloromethane for 19h; Ambient temperature; | |
1: 85% 2: 6 %Chromat. | With dihydrogen peroxide In lithium hydroxide monohydrate at 25℃; for 2h; Green chemistry; | Gram-scale oxidation of thioanisole using Ti-MWW catalyst (as a typical procedure for isolation) A test tube equipped with a magnetic stirring bar was charged with thioanisole (1.24 g, 10.0 mmol), aqueous 30% H2O2(1.16 g, 10.2 mmol), and Ti-MWW (100.2 mg). The mixture was vigorously stirred at 25 °C for 2 h. The organic phase was separated, and the organic phase was washed with saturated aqueous Na2S2O3 (10 mL). The organic phase was purified by column chromatography on silica gel using 5:1 hexane / ethylacetate as an eluent to give methyl phenyl sulfoxide as colorless crystals; yield: 1.36 g (85%). |
1: 85% 2: 12% | With tetra-n-butylammonium tetrafluoroborate; oxygen In dichloromethane at 20℃; for 2h; Electrochemical reaction; Green chemistry; | |
1: 7% 2: 84% | With (hydrotris(3,5-diphenyl-pyrazol-1-yl)borate)Fe(II)(benzilate); oxygen In acetonitrile; benzene at 20℃; for 0.25h; | |
1: 83% 2: 7% | With dihydrogen peroxide In methanol; lithium hydroxide monohydrate at 20℃; for 0.5h; | |
82% | With sodium bromite; "wet" H(1+)-exchanged zeolite F-9 In dichloromethane for 1h; Ambient temperature; | |
1: 81% 2: 8% | With oxygen; 3-methylbutyrylaldehyde In 1,2-dichloro-ethane at 40℃; for 1h; | |
1: 81% 2: 8% | With iron(III) oxide; oxygen; 3-methylbutyrylaldehyde In 1,2-dichloro-ethane at 40℃; for 1h; | |
1: 81% 2: 14% | With dihydrogen peroxide In acetonitrile at 20℃; for 5h; | 2.5. Oxygenation reactions General procedure: Oxygenation reactions of organic sulfides were carried out similarly to similar homogeneous reactions described in literature [12]. The heterogeneous catalyst II was used in quantities that were calculated to give approximately 1 mol% loading of 1 with respect to 0.5 mmol organic sulfide substrate. All reactions were carried out in duplicate. Specific reaction conditions were: 0.20 g catalyst I or II, 0.50 mmol organic sulfide substrate, and 0.40 mmol 1,2-dichlorobenzene for internal standard. The reactions were run in 5 mL of acetonitrile at room temperature, and the heterogeneous catalyst was kept in suspension with vigorous stirring. Each reaction was initiated by the rapid addition of 2.0 equiv. of hydrogenperoxide. Samples were taken by removing 20 μL of the reaction mixture, followed by diluting to 60 μL with acetonitrile, shaking and centrifuging. After centrifugation, the samples were decanted into fresh centrifuge tubes to keep the sulfoxide/sulfone species from adsorbing to the silica. Six recycling reactions were completed with both catalysts I and II. These reactions used methyl phenyl sulfide for the model substrate. The recycling procedure involved filtering off the heterogeneous catalyst from the MeCN solutions of both the parallel reactions, and then after rinsing and drying, separating the material into halves for the next parallel reaction Finally a few other substrates: methyl p-tolyl sulfide, phenylsulfide, benzothiophene, and dibenzothiophene were used to test the versatility of catalyst II. The reactions of the last three substrates were completed at 40°C to accelerate the otherwise slow reactions. |
1: 80% 2: 10% | With urea-hydrogen peroxide at 85℃; for 0.25h; | |
1: 80% 2: 10% | With [(hydrotris(3,5-diphenylpyrazole-1-yl)borate)FeII(mandelate)(H2O)] | |
1: 80% 2: 10% | With (hydrotris(3,5-diphenyl-pyrazol-1-yl)borate)Fe(II)(benzilate); oxygen In benzene at 20℃; for 0.333333h; | |
1: 76% 2: 15% | With 1H-imidazole; tetra-n-butylammonium peroxomonosulfate In dichloromethane at 25℃; for 0.0333333h; chemoselective reaction; | |
1: 75% 2: 25% | With dihydrogen peroxide In lithium hydroxide monohydrate at 25℃; for 0.5h; | |
1: 74% 2: 26% | With dihydrogen peroxide at 50℃; for 4h; | |
1: 13.3% 2: 74.8% | With [manganese(II)(4,11-dimethyl-1,4,8,11-tetraazabicyclo[6.5.2]pentadecane)Cl2]; dihydrogen peroxide In acetonitrile at 29.84℃; for 6h; | |
1: 74% 2: 72% | With dihydrogen peroxide In lithium hydroxide monohydrate at 30 - 35℃; for 24h; Sealed tube; Green chemistry; | 2.3 General procedure for the oxidation of sulfoxide/sulfone from sulfide compounds General procedure: A mixture of sulfide (1 mmol) and H2O (2 mL) wastaken in a stoppered tube. Then 1.2/2.5equiv. of 50%H2O2 was added slowly to it. The reaction mixture wasstirred at room temperature. The progress of the reactionwas monitored by TLC or GC. After 24 h, the productwas extracted with ethyl acetate (3 x5 mL). The organiclayer was separated, dried (Na2SO4), and concentratedunder vacuum. The crude products were purified bycolumn chromatography using silica gel (60-120 mesh)with petroleum ether and ethyl acetate as solvent to getthe pure product. The pure products were analyzed by13C, 1H NMR spectra and gas chromatography massspectrometer (GCMS). |
1: 70% 2: 30% | With dibenzo-18-crown-6; dihydrogen peroxide In ethanol at 45℃; for 8h; | |
1: 70% 2: 25% | With urea-2,2-dihydroperoxypropane In tetrahydrofuran at 20℃; for 0.416667h; Green chemistry; | Typical Procedure for Selective Oxidation of Methyl(phenyl)sulfide Sulfides to (methylsulfinyl)benzene and(methylsulfonyl)benzene General procedure: To a stirred solution of sulfide (1 mmol, 0.124 g) and THF (4 mL), urea-2,2-dihdroperoxypropane (2 or 6 mmol, 0.336-1.00 g pending to products) was added and the mixture was stirred at room temperature for an appropriate time. After completion of the reaction as monitored by TLC, saturated aqueous solution of Na2SO3 (2 mL of 1 M solution) was added to quench the excessive oxidant remaining in the mixture. Then water (10 mL) was added to the mixture and extracted using chloroform (3 × 5 mL) and dried over anhydrous MgSO4. After evaporation of solvent under reduced pressure, chromatography on silica gel was used to give pure products. |
1: 69% 2: 27% | With C4H9N2O9W In methanol; lithium hydroxide monohydrate at 20℃; for 0.75h; | |
1: 69% 2: 13% | With (Bu4N)2[{MoO(O2)2}2(μ-O)]; dihydrogen peroxide In acetonitrile for 2.5h; | Encouraged by the proficiency of 1 in the oxygenation of MPS,the catalytic performance of 1 was examined with additional substrateslisted in Chart 1 under the same conditions as those for theMPS reaction, and the results are collected in Table 1. Using oneequiv of H2O2, the reaction of BPS produced 53% sulfoxide and23% sulfone at 3 h, which indicates both a 100% utility of H2O2and lack of selectivity for sulfoxide. With 2.0 equiv of H2O2, BPSwas converted to the corresponding sulfone at 24 h. Compared tothe reactions of MPS and BPS, the reaction with PPS is significantlyslower, yielding 50% sulfoxide and 30% sulfone at 4 h. The reactionwith 4BT was slightly faster than that of MPS and resulted in 81%sulfoxide and 5% sulfone in 0.5 h (TOF: 910 h1). Lastly, PTEproceeded to 66% sulfoxide and 9% sulfone in 0.5 h for a TOF of660 h1. At 24 h, the reaction with PTE still contained 10% sulfoxidealong with 86% sulfone. This is possibly due to the conversionof PTE to the corresponding aldehyde as a minor side product |
1: 67% 2: 8.5% | With calcium hypochlorite In ethyl acetate for 1.5h; Heating; | |
1: 33.3% 2: 66.7% | With dihydrogen peroxide In lithium hydroxide monohydrate at 25℃; for 1h; | |
1: 65.6% 2: 34.4% | With glacial acetic acid In Carbon tetrachloride at 20℃; for 1.16667h; var. org. S compounds, temperatures, oxidizing agent/educt ratios, acetic acid concentrations, solvents; | |
1: 24.5% 2: 65.7% | With [MnIV(4,10-dimethyl-1,4,7,10-tetraazabicyclo[5.5.2]tetradecane)(OH)2](PF6)2; dihydrogen peroxide; calcium trifluoromethane sulfonate In acetonitrile at -0.16℃; for 4h; | |
1: 65% 2: 30% | With urea-2,2-dihydroperoxypropane In tetrahydrofuran at 20℃; for 0.666667h; Green chemistry; | Typical Procedure for Selective Oxidation of Methyl(phenyl)sulfide Sulfides to (methylsulfinyl)benzene and(methylsulfonyl)benzene General procedure: To a stirred solution of sulfide (1 mmol, 0.124 g) and THF (4 mL), urea-2,2-dihdroperoxypropane (2 or 6 mmol, 0.336-1.00 g pending to products) was added and the mixture was stirred at room temperature for an appropriate time. After completion of the reaction as monitored by TLC, saturated aqueous solution of Na2SO3 (2 mL of 1 M solution) was added to quench the excessive oxidant remaining in the mixture. Then water (10 mL) was added to the mixture and extracted using chloroform (3 × 5 mL) and dried over anhydrous MgSO4. After evaporation of solvent under reduced pressure, chromatography on silica gel was used to give pure products. |
1: 65% 2: 35% | With dihydrogen peroxide at 20℃; for 24h; | 2.2. General procedure for the oxidation of sulfides tosulfoxides using 30% H2O2 in the presence of H-ZSM5 as acatalyst General procedure: H-ZSM5 (12 mg) was added to a mixture of sulfide (1 mmol) and 30% H2O2 (2.4 equiv), then the mixture was stirred at room temperature under solvent-free conditions and the progress of the reaction was monitored by Thin-layer chromatography (TLC) (EtOAc/n-hexane, 1/2). After completion of the reaction, EtOAc (5 mL) was added, the catalyst was separated by filtration, and washed with additional EtOAc (5 mL). The organic layer was washed with brine (5 mL) and dried over anhydrous Na2SO4. Finally, the organic solvent was evaporated, and products were obtained in good to high yield. All the products are known and were characterized by comparing their spectral and physical data with those of authentic samples. |
1: 63.34% 2: 36.6% | With dihydrogen peroxide In acetonitrile at 20℃; for 3h; | |
1: 37% 2: 63% | With sodium chlorine monoxide; C75H102Cl3Fe3N6O6 In dichloromethane at 20℃; chemoselective reaction; | |
1: 34% 2: 62% | With dihydrogen peroxide In methanol; lithium hydroxide monohydrate at 20℃; for 0.5h; | |
1: 61% 2: 2 % Spectr. | With dihydrogen peroxide; scandium trifluoromethanesulphonate In ethanol; dichloromethane; lithium hydroxide monohydrate at 20℃; for 6h; | |
1: 60% 2: 3% | With (S)-norcamphor-based tertiary hydroperoxide In toluene at -20℃; for 1h; | |
1: 58% 2: 42% | With sodium chlorine monoxide; C75H102Cl3Fe3N6O6 In dichloromethane at 20℃; chemoselective reaction; | |
1: 58% 2: 25% | With C36H27CuN8O2; dihydrogen peroxide In methanol; dichloromethane at 0℃; for 10h; | 2.8. General procedure for oxidation of organic thioethers General procedure: All the catalytic reactions were performed by a similar procedure.To a solution of 3 mmol of sulfide and 5 mL of 30% H2O2 in methanol-dichloromethane (1:9), 0.0120 mmol of catalyst 4a wasadded at 0 °C. The reaction mixture was stirred for 10 h. The solution was concentrated in a vacuum. The products were separatedby preparative TLC using benzene-acetonitrile (95:5) mixed solvent. Yields were determined by weighing the isolated products,which were characterized by 1H NMR and IR spectroscopy (Table 4). |
1: 39.1% 2: 57.1% | With 1H-imidazole; urea hydrogen peroxide addition compound; glacial acetic acid In ethanol at 25℃; for 0.166667h; Green chemistry; | |
57% | With 1,3,5-trichloro-2,4,6-triazine; urea hydrogen peroxide addition compound In acetonitrile at 20℃; for 1.5h; | General procedure for oxidation of sulfides into sulfoxides using urea-hydrogenperoxide adduct (UHP) and cyanuric chloride: General procedure: To a solution of sulfide (1.0 mmol) and UHP (2.0 or 1.0 mmol according to the sulfide) in CH3CN (20 mL) wasadded cyanuric chloride (2.0 or 1.0 mmol according to the sulfide). The resulting solution was stirred until the sulfone was generated by TLC monitoring at room temperature and then quenched with H2O. The reaction mixture was extracted repeatedly with CH2Cl2. The organic layer was separated and concentrated in vacuo. The residue was subjected to flash column chromatography with hexanes/EtOAc (5:1 - 1:8) as eluent to afford the corresponding sulfoxide. |
55% | With 2-([di(2-pyridyl)methyl](methyl)amino}methyl)phenol; dihydrogen peroxide; manganese(III) triacetate In propan-2-one at 0℃; for 4h; | |
1: 55.1% 2: 35.7% | With 1H-imidazole; urea hydrogen peroxide addition compound; glacial acetic acid In ethanol at 0℃; for 0.166667h; Green chemistry; chemoselective reaction; | |
1: 45% 2: 55% | With C19H13N3O4V; dihydrogen peroxide In methanol; dichloromethane at 0 - 4℃; for 2.5h; | Catalytic oxygenation of thioethers General procedure: To a solution of PhSMe (465 mg, 3.75 mmol) in methanol-dichloromethane (10:90 v/v), the catalyst [(L1)VO] (6.0 mg,0.015 mmol) and 50% H2O2 (1 mL) were added at 0 °C. The mixture was stirred for 2.5 h keeping the temperature at 0-4 °C. The solution was then dried in a vacuum. The products were isolated by thin layer chromatography (TLC). The solid PhSOMe and PhSO2Me were isolated as the third and second fractions, respectively, with yields of 187 mg and 222 mg, respectively. The products were characterised by IR spectroscopy. The results of the conversions of other thioethers to sulfoxides and sulfones are given in Table 2. |
1: 54% 2: 30% | With (S)-norcamphor-based tertiary hydroperoxide In toluene at -20℃; for 5h; | |
1: 54.7% 2: 22.1% | With 1H-imidazole; Fe(TPP)OAc; tetrabutylammonium (meta)periodate In dichloromethane at 20℃; for 4h; | General oxidation procedure General procedure: Stock solutions of the metalloporphyrins (0.003 M)and ImH (0.5 M) were prepared in CH2Cl2. In a typicalreaction, sulfide or olefin (0.25 mmol), Mn-porphyrin(0.003 mmol, 1 ml) and ImH (0.015 or 0.03 mmol, 30 or60 μl, see the text) were added into a 10 ml round bottomflask containing 1 ml of CH2Cl2. Then, 0.5 mmol (0.217 g)TBAP was added. The mixture was stirred thoroughly for4 h at ambient temperature. After the required time, 5 ml ofdiethyl ether was added to the flask and the reaction mixturepassed through a short silica gel column to remove theunreacted TBAP and any remaining metalloporphyrin. Lowsolubility of TBAP in ether led to the precipitation of unreactedoxidant following the addition of ether to the reactionmixture. Also, the used metalloporphyrins are slightly solublein ether and were separated by chromatography througha short silica gel column. The resulting solution was analyzedby GLC. 1H NMR was used to analyze the productsin the case of cis- and trans-stilbene. All reactions wererepeated at least three times, analyzed by GC and averaged. |
1: 52% 2: 48% | With 2,3,5,6,8,9,11,12,14,15-decahydro-1,4,7,10,13,16-benzohexaoxacyclooctadecin; dihydrogen peroxide In ethanol at 45℃; for 8h; | |
1: 51.9% 2: 48.1% | With 1H-imidazole; CH3CO2Fe(tetraphenylporphyrin(p-OCH3)4); tetrabutylammonium (meta)periodate In dichloromethane at 20℃; for 4h; | General oxidation procedure General procedure: Stock solutions of the metalloporphyrins (0.003 M)and ImH (0.5 M) were prepared in CH2Cl2. In a typicalreaction, sulfide or olefin (0.25 mmol), Mn-porphyrin(0.003 mmol, 1 ml) and ImH (0.015 or 0.03 mmol, 30 or60 μl, see the text) were added into a 10 ml round bottomflask containing 1 ml of CH2Cl2. Then, 0.5 mmol (0.217 g)TBAP was added. The mixture was stirred thoroughly for4 h at ambient temperature. After the required time, 5 ml ofdiethyl ether was added to the flask and the reaction mixturepassed through a short silica gel column to remove theunreacted TBAP and any remaining metalloporphyrin. Lowsolubility of TBAP in ether led to the precipitation of unreactedoxidant following the addition of ether to the reactionmixture. Also, the used metalloporphyrins are slightly solublein ether and were separated by chromatography througha short silica gel column. The resulting solution was analyzedby GLC. 1H NMR was used to analyze the productsin the case of cis- and trans-stilbene. All reactions wererepeated at least three times, analyzed by GC and averaged. |
1: 50% 2: 10% | With potassium permanganate; glacial acetic acid In dichloromethane for 3h; Ambient temperature; | |
1: 25% 2: 50% | With C35H32ClCu2N2O7S2(1+)*ClO4(1-)*H2O; dihydrogen peroxide In methanol; dichloromethane at 0℃; for 2h; | 2.4 General procedure for the catalytic oxygenation of thioethers General procedure: Two catalytic reactions were performed by a similar procedure. To a solution of the catalyst [Cu2(L)(μ-OH)](ClO4)2 (0.0125 mmol) in methanol-dichloromethane (1:9) mixed solvent, 2.8 mmol of sulfide and 1mL of 50% H2O2 were added at 0 °C. The reaction mixture was stirred for 2 h. The solution was then dried in vacuum. The products were separated and purified by preparative TLC using benzene-acetonitrile (95:5) mixed solvent. The products were characterized by IR and 1H NMR spectra. |
1: 20% 2: 50% | With UHP, urea hydrogen peroxide complex; C15H19MoNO9 In ethanol at 20℃; for 0.25h; | 2.7 General Procedure for Selective Oxidationof Thioanisole to Methyl Phenyl Sulphoxide General procedure: To a mixture of molybdenum complexes (1-4; 0.05 mmol)and thioanisole (1 mmol) in 3 mL of ethanol, UHP(1 mmol) was added and the reaction mixture was stirred atroom temperature. The progress of reaction was monitoredby TLC as well as HPLC. The reaction mixture was concentratedunder reduced pressure and the pure product wasisolated by column chromatography using silica gel assolid support and a mixed solvent (n-hexane/ethyl acetate70:30) as eluent. |
1: 48% 2: 40% | With C19H15N3O4V; dihydrogen peroxide In methanol; dichloromethane; lithium hydroxide monohydrate at 0 - 4℃; for 2.5h; | |
1: 44.3% 2: 46.5% | With Mn<SUP>II</SUP>(Me<SUB>2</SUB>EBC)Cl<SUB>2</SUB>; dihydrogen peroxide In acetonitrile at 29.84℃; for 6h; | |
1: 44.3% 2: 46.5% | With Mn<SUP>II</SUP>(Me<SUB>2</SUB>EBC)Cl<SUB>2</SUB>; dihydrogen peroxide In acetonitrile at 29.84℃; for 6h; | |
1: 44.1% 2: 37.1% | With dichloro(4,10-dimethyl-1,4,7,10-tetrazabicyclo[5.5.2]tetradecane)manganese(II); dihydrogen peroxide; calcium trifluoromethane sulfonate In acetonitrile at 29.84℃; for 6h; | |
1: 41% 2: 5.1% | With iodosylbenzene In 1,2-dichloro-ethane at 40℃; for 4h; | |
1: 40% 2: 5% | With potassium peroxomonosulfate; C26H40ClMnN2O8Si2 In lithium hydroxide monohydrate at 25℃; for 0.5h; Green chemistry; | |
1: 40% 2: 30% | With 20H2O*11K(1+)*H(1+)*H6O74P2Sn3W18(12-); dihydrogen peroxide In lithium hydroxide monohydrate at 25℃; for 10h; | |
1: 40% 2: 35% | With C19H14CuN4O; dihydrogen peroxide In methanol; dichloromethane at 0℃; for 6h; | 2.4. General procedure for catalytic oxygenation of thioethers General procedure: To the catalyst Cu(L) (0.014 mmol) dissolved in 10 mL dichloromethane-methanol (8:2) mixed solvent, 3 mmol of sulfide and 1.5mL of 50% H2O2 were all inserted in a 25 mL round-bottom flask at 0C. The mixture was stirred for 6 h. After the completion of the reaction the mixture was evaporated to dryness, water was addedand the product was extracted with dichloromethane. The organic layer was washed with brine, dried over Na2SO4, filtered. The products were separated and purified by preparative TLC using hexane-ethyl acetate (2:1) mixed solvent. The yields of the products obtained from all the reactions were determined after isolation,and characterized by1H NMR and IR spectra |
1: 35% 2: 14% | With 1H-imidazole; Mn(TPP)OAc; tetrabutylammonium (meta)periodate In dichloromethane at 25℃; for 4h; | General Oxidation Procedure General procedure: Stock solution of the catalyst (0.003 M) and imidazole (ImH,0.5 M) were prepared in CH2Cl2. In a test tube, the reagents were added in the following order: substrate (0.25 mmol), catalyst (0.003 mmol, 1.0 mL), ImH (0.03 mmol, 60 mL), chlorobenzene (1 mmol) as an internal standard. TBAP(167 mmol) was then added to the reaction solution at 25 °C. The reaction solutions were analyzed by GC after stirring for 4 h. |
1: 35% 2: 9% | With dihydrogen peroxide In lithium hydroxide monohydrate; acetonitrile at 30℃; for 2h; | |
1: 32% 2: 26% | With 1H-imidazole; Mn(TPP)OAc; tetrabutylammonium (meta)periodate In dichloromethane at 25℃; for 4h; | General Oxidation Procedure General procedure: Stock solution of the catalyst (0.003 M) and imidazole (ImH,0.5 M) were prepared in CH2Cl2. In a test tube, the reagents were added in the following order: substrate (0.25 mmol), catalyst (0.003 mmol, 1.0 mL), ImH (0.03 mmol, 60 mL), chlorobenzene (1 mmol) as an internal standard. TBAP(167 mmol) was then added to the reaction solution at 25 °C. The reaction solutions were analyzed by GC after stirring for 4 h. |
1: 30% 2: 26% | With (tetraphenylporphinato)manganese(III) acetate; tetrabutylammonium (meta)periodate In dichloromethane at 25℃; for 4h; | |
1: 29% 2: 21% | With (N,N'-ethylenebis(salicylideneaminato))oxovanadium(V) trifluoromethanesulfonate; dihydrogen peroxide In acetonitrile at 20℃; for 24h; | H2O2 (6.0 mmol) was slowly added to a 5.6 mmol solution of PhSMe inacetonitrile containing 0.01 mmol VO(salen)CF3SO3 and stirred at room temperature for 24 hrs. After complete consumption of theoxidant and usual work-up, the crude product was chromatographed on a silicagel column, eluting with solvents of increasing polarity (dichloromethane, ethylacetate and methanol), 29% PhSOMe and 21% PhSO2Me were obtained,>99% pure at the GC analysis. |
1: 11% 2: 28% | With [(tris(6-methyl-2-pyridylmethyl)amine)FeII(benzilate)](ClO4); oxygen In acetonitrile at 20℃; | |
1: 14% 2: 25% | With dihydrogen peroxide In lithium hydroxide monohydrate; acetonitrile at 60℃; for 2h; chemoselective reaction; | |
1: 25% 2: 25% | With dihydrogen peroxide In lithium hydroxide monohydrate; acetonitrile at 20℃; for 2h; | |
24% | With C28H39N2O5PolTi; dihydrogen peroxide In 1,2-dichloro-ethane at 0℃; for 24h; enantioselective reaction; | |
1: 16% 2: 7% | With tris(2,4-pentanedionato)iron(III); 2-(salicylideneamino)-2-methyl-1-hydroxyethane; 2,6-dimethoxybenzoic acid sodium salt; dihydrogen peroxide In dichloromethane at 0℃; for 20h; | 8 Production of Methyl Phenyl Sulfoxide (1) Preparation of Catalyst Solution. Fe(acac)3 (1.8 mg, 0.005 mmol), a compound of the formula (3-4) (1.0 mg, 0.005 mmol), a compound of the formula (4-1) (Sodium 2,6-dimethoxybenzoate; 5.1 mg, 0.025 mmol), and dichloromethane (1 mL) were added to a vial equipped with a screw cap. The mixture was stirred at room temperature for 30 minutes. (2) Production of Titled Compound.Thioanisole (62.1 mg, 0.500 mmol) was dissolved in dichloromethane (1.0 mL). The catalyst solution prepared in (1) above was added thereto. The mixture was cooled to 0° C. 30% hydrogen peroxide (113.4 mg, 1.0 mmol) was added thereto. The mixture was stirred at 0° C. for 20 h. The organic layer of the reaction mixture was analyzed by HPLC (area percentage). As a result, the components excluding the solvent etc. in the reaction mixture were as follows; methyl phenyl sulfoxide (titled compound): 16%, thioanisole (starting compound): 77%, methylphenylsulfone (byproduct by excess oxidation): 7%. LC/MS of titled compound; Exact Mass: 140.0, measured value (positive): 141.1 LC/MS of byproduct; Exact Mass: 156.0, measured value (positive): 157.1 |
1: 9% 2: 16% | With oxygen; C41H40FeN5O3(1+)*ClO4(1-) at 20℃; for 2h; | |
1: 15% 2: 10% | With potassium peroxomonosulfate In chloroform at 25℃; for 3h; Green chemistry; | |
10% | With dihydrogen peroxide; MoO<SUB>2</SUB>(methanol)(2-((pyrrolidin-2-ylidenehydrazineylidene)methyl)phenolate) In methanol; dichloromethane; lithium hydroxide monohydrate at 9.84℃; for 18h; Overall yield = 83 percent; | |
With cytochrome P-450; D-glucose 6-phosphate dehydrogenase (G6P-DH); Emalgen 913; reductase; NADP for 1h; Ambient temperature; other sulfides, sulfoxides and sulfones; other enzymes; reaction with hydroxy radicals; | ||
1: 60 % Spectr. 2: 10 % Spectr. | With Sodium hydrogenocarbonate; ozone In lithium hydroxide monohydrate; acetonitrile various substrates and variation of O3/NaHCO3 ratio; | |
1: 12 % Chromat. 2: 46 % Chromat. | With methyltrifluoromethyldioxirane In dichloromethane at 0℃; with different solvent; | |
With iodosylbenzene In dichloromethane for 0.25h; Yield given. Yields of byproduct given; | ||
With sodium (meta)periodate In methanol; lithium hydroxide monohydrate at 25℃; Yield given. Yields of byproduct given; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With N-(iodyl-4 phenyl) palmitoylamid In benzene at 80℃; for 0.5h; | |
96% | With tetrahexylammonium tetrakis(diperoxomolybdo)phosphate In chloroform at 40℃; for 1.7h; | |
95% | With n-C4F9; perfluoro-cis-2,3-dialkyloxaziridine; n-C3F7 In chloroform; trichlorofluoromethane at -20℃; for 0.25h; |
94% | With copper(II) phthalocyanine; tetra-n-butylammonium peroxomonosulfate In water monomer at 25℃; for 1h; | |
94.61% | With selenium(IV) dioxide; dihydrogen peroxide In dichloromethane for 4.25h; Reflux; | 3 In a 100 mL three-necked flask, 15 mL of dichloromethane was added, followed by 10 mmol of dimethyl sulfoxide and 10 mmol of selenium dioxide, and stirring was started to disperse the materials uniformly. Under stirring, 15 mmol of 30% hydrogen peroxide was added dropwise within 15 min, and heated to reflux for 4 hrs. The material was concentrated under reduced pressure to obtain a solid product with a yield of 94.61%. |
91% | With dihydrogen peroxide In water monomer; acetonitrile at 19.84℃; for 3h; chemoselective reaction; | |
87% | Stage #1: racemic methyl phenyl sulfoxide With ozone In methanol at -20℃; Stage #2: With dihydrogen peroxide In methanol at -10℃; | |
85% | With ((2,2'-(ethane-1,2-diylbis[(nitrilo-κN)methylidyne])bis(phenolato-κO))(2-))manganese(1+) hexafluorophosphate; dihydrogen peroxide In water monomer; acetonitrile at 25℃; Inert atmosphere; | |
79% | With iodosylbenzene; (salen)MnIII In acetonitrile at 25℃; for 0.833333h; | |
78% | With 18-crown-6 ether In dichloromethane Ambient temperature; | |
73% | With sodium chlorine monoxide In acetonitrile for 0.5h; Ambient temperature; | |
51.5% | With dichloro(4,10-dimethyl-1,4,7,10-tetrazabicyclo[5.5.2]tetradecane)manganese(II); dihydrogen peroxide; calcium trifluoromethane sulfonate In acetonitrile at -0.16℃; for 2h; | |
50% | With dihydrogen peroxide In acetonitrile at 27℃; for 0.5h; | |
44.7% | With dihydrogen peroxide In n-Pentane | 11 Oxidation of Sulfoxide for Preparing Sulfone EXAMPLE 11 Oxidation of Sulfoxide for Preparing Sulfone 40 mmol of methyl phenyl sulfoxide was dissolved in 20mL of n-pentane. To the solution was added 20 mmol of 85% aqueous solution of hydrogen peroxide and then 0.1 mmol of catalyst [(n-C4H9)4N]3[AsW12O40]. The reaction was conducted at 0° C. for 2 hours. At this time, catalyst separated out from the reacting system. The conversion of methyl phenyl sulfoxide was 44.7% and the yield of methyl phenyl sulfone was 40.1%. After the separated catalyst was recovered by filtration and vacuum dried, it could be recycled in the above reaction. Example 11 was repeated except that the substrate, solvent and reaction temperature of the reacting system were changed, and the results of the oxidation reaction were shown in the following table. |
15% | With dihydrogen peroxide In acetonitrile at 27℃; for 24h; | |
12% | With para-iodoanisole; tetra-n-butylammonium acetate; tetra-n-butylammonium hexafluoridophosphate In methanol at 25℃; Electrolysis; | |
4% | With cerium(III) sulphate; barium bromate In water monomer; acetonitrile at 20℃; for 23.3333h; | |
With cytochrome P-450; reductase; oxygen; NADPH In water monomer at 24.5℃; phosphate buffer, pH 7.4; one electron transfer; | ||
With N5-ethyl-4a-hydroperoxy-3-methyllumiflavin In 1,4-dioxane at 30℃; | ||
With 3,3-dimethyldioxirane In decane; acetone Ambient temperature; relative rates of oxidation with p-substituted aryl methyl sulfoxides; | ||
With dihydrogen peroxide In ethanol; water monomer at 40℃; other sulfoxides and sulfones, acidic or alkaline conditions, other oxidants; | ||
With <MoO(O2)2L>(1-)*Bu4N(1+) L=C5H4NCO2(1-) (1) In 1,2-dichloro-ethane at 40℃; various molybdenum peroxo complexes as oxidants; various temperatures, solvents, additives, and concentrations; | ||
With Davis oxaziridine In chloroform-d1 at 25℃; | ||
With 4a-FlEt-OOH In 1,4-dioxane at 30℃; | ||
With anhydrous sodium perchlorate; oxalic acid; potassium carbonate In glacial acetic acid at 40℃; add of aluminum nitrate or acrylamide; HClO4; var. temp.; | ||
With tetrahexylammonium tetrakis(diperoxomolybdo)phosphate In chloroform at 40℃; other sulfones; | ||
With potassium bromate; sulfuric acid; mercury (II) acetate In glacial acetic acid at 35℃; other temperatures, ΔH(excit.), ΔS(excit.); | ||
With dihydrogen peroxide; acetonitrile In methanol at 0℃; | ||
With sodium hydroxide; chloramine-T In water monomer; <i>tert</i>-butyl alcohol at 35℃; var. concn. of reactants, hydroxide, and catalyst; ionic strength; | ||
With N-Brom-ε-caprolactam; mercury (II) acetate; glacial acetic acid In water monomer at 30℃; further reagent; | ||
With adamantanone azide; oxygen; [7-(dimethylamino)phenothiazin-3-ylidene]dimethylazanium chloride In dichloromethane at 15℃; Irradiation; Yield given; | ||
With potassium superoxide; 2-Nitrobenzenesulfonyl chloride In acetonitrile at -30℃; for 0.166667h; | ||
With iodosylbenzene; (salen)MnIII In acetonitrile at 19.85℃; | ||
With iodosylbenzene; (salen)MnIII In acetonitrile at 29.85℃; | ||
With iodosylbenzene; (salen)MnIII In acetonitrile at 39.85℃; | ||
With iodosylbenzene; (salen)MnIII In acetonitrile at 19.85 - 39.85℃; ΔH(excit.), ΔS(excit.); | ||
With 2-diphenylphosphinoyl-3-methyl-3-trifluoromethyloxaziridine In chloroform-d1 at 35.3℃; | ||
With perchloric acid; peroxomonophosphoric acid; anhydrous sodium perchlorate In water monomer; glacial acetic acid at 35℃; | ||
With hydrogenchloride; potassium peroxomonosulfate at 29.85℃; | ||
With tris(1,10-phenanthroline)iron(III) perchlorate at 24.85℃; | ||
With oxo(salen)chromium(V) perchlorate In acetonitrile at 24.85℃; | ||
With glucose-6-phosphate dehydrogenase; α-D-glucose 6-phosphate; Pseudomonas fluorescens ACB 4-OH-acetophenone monooxygenase; β-nicotinamide adenine dinucleotide phosphate, oxidized form for 20h; | ||
With glucose-6-phosphate dehydrogenase; α-D-glucose 6-phosphate; 4-hydroxyacetophenone monooxygenase; NADP for 20h; | ||
With potassium permanganate; anhydrous zinc chloride In acetone at 23℃; | ||
With Ru(III) complex with 2,2'-bipyridine In water monomer; acetonitrile at 24.84℃; | ||
100 % Chromat. | With 1H-imidazole; manganese(II) tetraphenylporphyrinate; tetra-n-butylammonium peroxomonosulfate In dichloromethane at 20℃; for 0.0166667h; | |
With ammonium nitrate; chloro-trimethyl-silane In dichloromethane at 50℃; for 2h; | ||
21 % Spectr. | With dihydrogen peroxide at 20℃; for 3h; | |
With dihydrogen peroxide In water monomer at 30℃; for 33h; | ||
61 %Chromat. | With sodium phosphite; NADPH In hexane; dimethyl sulfoxide at 25℃; for 8h; aq. buffer; Enzymatic reaction; optical yield given as %ee; | |
With pyridine; 1H-imidazole; acetato(tetrakis(2,4,6-trimethylphenyl)porphyrinato)manganese(III); tetra-n-butylammonium peroxomonosulfate In dichloromethane at 20℃; for 0.0833333h; | ||
With titanium isopropoxide; tert.-butylhydroperoxide; (S)-2-[N-{3,5-bis(α,α-dimethylbenzyl)salicylidene}amino]-3,3-dimethyl-1-butanol In dichloromethane at 20℃; | ||
With C44H10F18N4O2Ru In chloroform at 23℃; | ||
With tert.-butylhydroperoxide; C78H60NO10V In dichloromethane at 0℃; enantioselective reaction; | ||
With tert.-butylhydroperoxide; P450 119 peroxygenase, wild-type In aq. phosphate buffer at 35℃; for 0.00833333h; Sealed tube; Enzymatic reaction; | ||
With dihydrogen peroxide In water monomer; acetonitrile at 60℃; | ||
With tungsten oxide; dihydrogen peroxide In d(4)-methanol for 0.5h; | ||
With cobalt; peroxymonosulfate at 25℃; for 0.0833333h; Flow reactor; | ||
92 %Chromat. | With thio-xanthene-9-one; oxygen In butanone at 35 - 40℃; Schlenk technique; UV-irradiation; Green chemistry; | 4.1. A typical procedure for the visible-light-promoted aerobic oxidation of sulfides 3 or sulfoxides1 in a ketone solvent General procedure: To a dried Schlenk tube equipped with a stirrer bar which wasevacuated and backfilled with oxygen, were added thioxanthone(10.6 mg, 0.05 mmol, 5.0% mol) and sulfide3 or sulfoxide 1(1.0 mmol), then 5 mL of DEK or MEK was added into the reactiontube via a syringe. The mixture was irradiated by a purple LED lampat 35e40C under oxygen atmosphere (1 atm). After 24 h, thesolvent was removed and the residue was purified byflash columnchromatography on silica gel to give the corresponding sulfone2.Methyl phenyl sulfone (2a):[7f] Purified by flash columnchromatography (hexanes/ethyl acetate1:1,Rf 0.5) obtained2ain 90% isolated yield (the aerobic oxidation of sulfide3). Whitesolid. M.P.: 85e87C.1H NMR (400 MHz, Chloroform-d)d7.97e7.94(m, 2H), 7.69e7.65 (m, 1H), 7.61e7.56 (m, 2H), 3.06 (s, 3H).13C NMR(101 MHz, Chloroform-d)d140.7, 133.8, 129.5, 127.5, 44.6. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With N,N,N,N,N,N-hexamethylphosphoric triamide; samarium diiodide In tetrahydrofuran at 20℃; for 0.166667h; | |
95% | With triethylsilane; tris(pentafluorophenyl)borate In neat (no solvent) at 100℃; for 8h; Glovebox; Inert atmosphere; | Reduction of Sulfoxides and Sulfones; General Procedure General procedure: In a glovebox, an oven-dried 1-mL screw-capped sealed tube with a magnetic stir bar was charged with B(C6F5)3 (10 mol%), Et3SiH (10 equiv), and the indicated oxidized sulfur compound (0.20 mmol). The tube was sealed properly and transferred to an oil bath preheated at100 °C. After 8 h, the reaction was cooled to r.t. and passed through asmall plug of silica gel using Et2O. The crude material was collected ina glass vial and subjected to GLC analysis to determine the conversion with respect to starting material. The ethereal solution was dried (Na2SO4) and filtered, and the solvent was removed under reduced pressure. The mixture was then subjected to high vacuum at 70 °C until the unreacted hydrosilane was removed from the system. If needed, the residue was purified further by flash column chromatography (silica gel, cyclohexane/Et2O 9:1) to afford the desired sulfides. |
With lithium aluminium tetrahydride; titanium tetrachloride In tetrahydrofuran at -78 - 20℃; for 0.5h; other sulfones; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With bromine; sodium hydroxide; at 75℃; for 5.0h; | General procedure: To a solution of NaOH (15% w/w, 8 mL) cooled to 5 C, Br2 (0.4 mL, 15 mmol, 3 equiv) was added dropwise while maintaining the temperature of the mixture below 10 C. Next, the sulfone (5 mmol, 1 equiv) was added in one portion. The resulting mixture was stirred for the given time (Table 1) at 75 C. The mixture was cooled to room temperature, and the precipitate filtered off, washed with H2O, dried in air, and crystallized from 2-PrOH. See Supplementary data for the characterization of the bromination products obtained |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43.59% | Stage #1: methylphenylsulfonate With n-butyllithium In tetrahydrofuran at 0℃; for 1h; Stage #2: With N,N,N,N,N,N-hexamethylphosphoric triamide In tetrahydrofuran at -78℃; for 1h; Stage #3: (S)-Propylene oxide In tetrahydrofuran at -78 - 20℃; for 2h; | 211 Synthesis of compound 211.2. Synthesis of compound 211.2. To a solution of 211.1 (20.0g, 128.04mmol, l .Oeq) in THF (250 mL) was added n-butyl lithium (18.04g, 0.281mmol, 2.2eq) at 0°C. Reaction was stirred at 0 °C for lh. HMPT (50.47g, 0.281mmol, 2.2eq) was added to the reaction mixture at -78 °C and the reaction was allowed to stir at -78 °C for lh. Further S-(-)-propylene oxide (15.24g, 0.262mmol, 2.05eq) dissolved in THF (50mL) was added to the reaction mixture at - 78 °C and the reaction was allowed to stir at room temperature for 72 h. After completion of the reaction, mixture was quenched with NH4C1 solution and extracted with EtOAc. Organic layers were combined, dried over sodium sulphate and concentrated under reduced pressure to give crude which was purified by column chromatography to furnish 211.2 (15.2g, 43.59%), MS (ES): m/z 272.36 [M+H]+. |
With n-butyllithium 1.) THF, HMPA, 0 -> -78 deg C, 2.) -78 deg C -> RT; Yield given. Multistep reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90.8% | With hydrogenchloride In tetrahydrofuran; hexane | 37 Preparation of (S)-1-[3,4-Dihydro-2,5,7,8-tetramethyl-6-(phenylmethoxy)-2H-1-benzopyran-2-yl]-3-(phenylsulfonyl)-2-propanone EXAMPLE 37 Preparation of (S)-1-[3,4-Dihydro-2,5,7,8-tetramethyl-6-(phenylmethoxy)-2H-1-benzopyran-2-yl]-3-(phenylsulfonyl)-2-propanone Methyl (S)-[3,4-dihydro-2,5,7,8-tetramethyl-6-(phenylmethoxy)-2H-1-benzopyran-2-yl]-acetate (25.8 g, 0.070 mole) was dissolved in 50 mL of dry THF contained in a 500 mL three-neck flask equipped with a magnetic stirring bar and argon inlet and outlet adaptors. The flask was swept with argon. Methyl phenylsulfone (10.94 g, 0.070 mole) was weighed into a 300 mL Schlenk tube equipped with a stirring bar and septum. The Schlenk tube was evacuated, refilled with argon, and charged with 150 mL of dry THF, using a syringe. The Schlenk tube and contents were chilled to 0°. A solution of 2.6M butyl lithum in hexane (2*27 mL=0.1404 mole) was added from a syringe in two portions. The second addition produced a creamy orange slurry of the dianion. After stirring for 15 minutes, this mixture was transferred via cannula to the three-neck flask containing the ester in THF. A 50 mL portion of THF was used to complete the transfer. After stirring the resulting mixture for 2 hours, the reaction mixture had warmed to room temperature and was quenched with 40 mL of 2N HCl. This mixture was transferred to a 1L separatory funnel. Hexane (100 mL) and brine (50 mL) were added and, after shaking, the layers were separated. The aqueous layer was extracted with 3*30 mL of CH2 Cl2. The combined organic layers were dried over MgSO4 and evaporated to a solid residue of crude product (43.7 g). This material was recrystallized from 500 mL of ethanol giving 31.3 g (90.8% yield) of (S)-1-[3,4-dihydro-2,5,7,8-tetramethyl-6-(phenylmethoxy)-2H-1-benzopyran-2-yl]-3-(phenylsulfonyl)-2-propanone as a pale yellow solid. A second crop of 4.0 g of less pure material was also obtained, but kept separate. An analytical sample was recrystallized from ethanol to give colorless crystals with m.p. 130°-8° and [α]D =+14.09° (c=0.9225, CHCl3). |
With n-butyllithium 1.) THF, hexane, 0 deg C, 15 min, 2.) THF, hexane, 0 deg C, 2 h; Yield given. Multistep reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.8 g | With sodium hydride In tetrahydrofuran; paraffin 1.) 0 deg C, 10 min, 2.) reflux, 2 h; | |
Stage #1: methylphenylsulfonate With sodium hydride In tetrahydrofuran at 0℃; Inert atmosphere; Stage #2: ethyl trifluoroacetate, In tetrahydrofuran at 0℃; Reflux; Inert atmosphere; | 32.1 Example 32; 5-(trifluoromethyl)thiazole-2-thiol; H2 step 6 step 7; Step 1 : To a stirred THF (20 mL) solution of methylsulfonylbenzene (1.60 g, 10 mmol) under N2 at O 0C was added NaH (60%, 600 mg, 15 mmol) in portions after which the resulting suspension was stirred at 0 0C for 10 min, and then treated dropwise with ethyl trifluoroacetate (3.60 mL, 30 mmol) at 0 0C.After 2 hrs under reflux, the resulting solution was poured into saturated aqueous NaCl(250 mL) and extracted with Et2O (100 mL x 4). The combined extracts were dried over MgSO4, and evaporated under reduced pressure to give l,l,l-trifluoro-3-(phenylsulfonyl)propan-2-one (1.80 g). The product was used without further purification in next step. | |
Stage #1: methylphenylsulfonate With sodium hydride In tetrahydrofuran at 0℃; for 0.166667h; Stage #2: ethyl trifluoroacetate, In tetrahydrofuran at 0℃; Reflux; | 16.1; 38.1 Step 1: To a stirred THF (20 mL) solution of methylsulfonylbenzene (1.60 g, 10 mmol) under N2 at O0C was added NaH (60%, 600 mg, 15 mmol) in portions after which the resulting suspension was stirred at O0C for 10 min, and then treated dropwise with ethyl trifluoroacetate (3.60 mL, 30 mmol) at O0C. After 2 hrs under reflux, the resulting solution was poured into saturated aqueous NaCl (250 mL) and extracted with Et2O (100 mL x 4). The combined extracts were dried over MgSO4, and evaporated under reduced pressure to give l,l,l-trifluoro-3- (phenylsulfonyl)propan-2-one (1.80 g). The product was used without further purification in next step. |
With sodium hydride In tetrahydrofuran | Examples of the invention, compounds (1) and (2), may be synthesized by the method described in the following reaction scheme. 2-Amino-5-trifluoromethyl-thiazole was prepared by a modification of the procedure of Laduron et al. J. Fluorine Chem. 1995, 73, 83-86. Coupling of o-acetylsalicyloyl choride and 2-Amino-5-trifluoromethylthiazole in the presence of a suitable base, including tertiary amines like triethylamine, in a suitable inert solvent like dichloromethane, at about 0 0C to about ambient room temperature, affords compound (1). Hydrolysis of the acetyl moiety of compound (1) with dilute hydrochoric acid at room temperature to about 50 0C yields compound (2). | |
Stage #1: methylphenylsulfonate With sodium hydride In tetrahydrofuran at 0℃; for 0.166667h; Inert atmosphere; Stage #2: ethyl trifluoroacetate, In tetrahydrofuran for 2h; Reflux; Inert atmosphere; | ||
With sodium hydride In tetrahydrofuran for 12h; Reflux; | 2. General procedure for the synthesis of Trifluoromethyl α-fluorinated arylsulfonyl gem-diols 1 1) To a stirred solution of sodium hydride (100 mmol) in THF (30 mL) was added the solution of triuoromethyl ethyl acetate (40 mmol) and methyl aryl sulfones (20 mmol) in THF (30 mL) dropwise. The mixture was stirred for 12 h under reflux. Then the reaction was diluted with 1 M HCl solution. The layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over MgSO4. The solvent was removed under reduced pressure, then puried by distillation or recrystallization to afford the 1,1,1-trifluoro-3-(arylsulfonyl)propan-2-ones. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 83% 2: 17% | With C22H19N2O5V; dihydrogen peroxide In acetonitrile at 40℃; | 2.8. Catalytic procedure Liquid phase catalytic oxidations of thionaisol were carried outunder air (atmospheric pressure) in a 25 mL round bottom flask equipped with a magnetic stirrer. In a typical experiment, H2O2 was added to a flask containing the catalyst (2 x 103 mmol) and thioanisol (1.0 mmol) in a solvent (3 mL). The course of the reaction was monitored using a gas chromatograph equipped with a capillary column and a flame ionization detector. The oxidation products were identified by comparing their retention times with those of authentic samples or alternatively by 1H NMR and GC-Mass analyses. Control reactions were carried out in the absence of catalyst, but otherwise under the same conditions as the catalytic runs. |
70% | Stage #1: methyl-phenyl-thioether With bis(acetylacetonate)oxovanadium; (R)-2-((1-hydroxy-3,3-dimethylbutan-2-ylimino)methyl)-4,6-diiodophenol In chloroform at 20℃; for 0.5h; Stage #2: With dihydrogen peroxide In chloroform at 0℃; for 16h; | |
30% | With (1S,2R,3R,4R)-2-OOH-2-(2'-furyl)-3-MeOCH2-bicyclo-heptane In toluene at -20℃; |
16% | With titanium(IV) isopropylate; tert.-butylhydroperoxide; (4S,5R)-4,5-dihydro-4,5-diphenyl-2-(2'-hydroxy-3'-tert-butylphenyl)-oxazoline In tetrachloromethane at 0℃; for 24h; | |
With dihydrogen peroxide In water; acetonitrile at 24.84℃; for 9h; Inert atmosphere; | ||
100 % ee | With [{Mn(H2O)2Cl2}2(2,3-O-4-hydroxybenzhydrazidebenzylidene-D-tartrate)]; dihydrogen peroxide In acetonitrile at 25℃; enantioselective reaction; | |
95 % ee | With glucose-6-phosphate dehydrogenase; glucose-6-phosphate; phenyl acetone monooxygenase P440L mutant; oxygen; NADPH In acetonitrile at 30℃; Enzymatic reaction; enantioselective reaction; | |
91 % ee | Stage #1: methyl-phenyl-thioether With titanium(IV) isopropylate; C51H54N2O4 In methanol; dichloromethane; water at 20℃; for 0.333333h; Inert atmosphere; Stage #2: With dihydrogen peroxide In methanol; dichloromethane; water at 0℃; for 1.5h; Inert atmosphere; enantioselective reaction; | |
96 % ee | With Gordonia terrae IEGM 136 cells immobilized into polyvinyl alcohol cryogel In water at 28℃; for 96h; Enzymatic reaction; | 2.4. Biotransformation of organic sulfides General procedure: 2.4. Biotransformation of organic sulfides Batch cultivations of immobilized cells were performed in100 mL Erlenmeyer asks containing 30 mL of the mineral mediumsupplemented with suldes or rac-MPSO on an orbital shaker(160 rpm) at 28 C. The biocatalyst (60 granules corresponds to5.0 ± 0.6 106 cells mL-1, and 8.0 ± 0.5 g (wet weight)/L) was rehy-drated in 0.5% NaCl for 24 h before use. The biotransformationprocess occurred for 24-72 h. As controls, sterile solutions of sul-des or rac-MPSO in a mineral medium, as well as PVA cryogelgranules containing no bacterial cells were used. Equal amounts offree and immobilized cells were used in the comparative experi-ments on biotransformation of organic suldes.In some experiments, sequential additions of MPS to the fermen-tation medium were applied. The initial MPS concentration was0.5 g/L. Each new portion of sulde (0.5, 0.75 or 1.0 g/L) was addedevery 24 h. Total load of MPS was 2.0, 4.25 or 5.5 g/L respectively.n-Hexadecane at a concentration of 0.1% (v/v) was introduced tothe medium additionally after 96 h of incubation. To monitor thesulfoxide production during MPS biotransformation, the samples(0.5 mL) were withdrawn from the culture broth under sterile con-ditions at 24 h intervals over 168 h.The long-term stability of immobilized cells was shown inbiocatalyst reuse MPS biotransformation studies. After each incu-bation cycle (24 h/cycle), the used medium was decanted and PVAcryogel-immobilized cells were washed three times with 0.5% NaClsterile solution and transferred into the fresh mineral mediumcontaining 0.5 g/L MPS and 0.1% (v/v) n-hexadecane. A biotransfor-mation process was carried out and residual MPS and bioconversionproducts were assayed in the post-fermentation medium. |
97 % ee | With dihydrogen peroxide; 6,6′-bis[(S)-4-isopropyloxazolin-2-y1]-2,2′-bipyridine; iron(II) chloride In tetrahydrofuran; water at -25℃; for 3h; enantioselective reaction; | |
> 99 % ee | With magnesium(II) chloride hexahydrate; D-glucose; recombinant fusion protein cyclohexanonemonooxygenase from Thermocrispum municipale with cofactor glucose dehydrogenase from Sulfolobus tokodaii; NADP In aq. phosphate buffer at 30℃; for 24h; Enzymatic reaction; enantioselective reaction; | 4.3. Conversion of cyclohexanone and derivatives, cyclopentanone,cyclobutanone and thioanisole using self-sufficient TmCHMOs General procedure: Purified self-sufficient TmCHMOs (2 mM or 4mM) wereemployed for biotransformation of cyclohexanone (5e25 mM), 4-methylcyclohexanone (5 mM), cyclopentanone (5 mM), cyclobutanone(5 mM) and thioanisole (5 mM) at 30 C (F-B and P-B) or24 C (G-B) and 250 rpm. All reactions contained 1 or 0.5 mmolNADPH, the co-substrate (10mM glucose for G-B, 50mM sodiumformate for F-B and 20mM sodium phosphite for P-B) and 100mMphosphate buffer pH 8.5. Additionally, G-B fusion needs theexternal addition of magnesium chloride (1 mM). In some cases, acosolvent (1% v/v 1,4-dioxane,1% v/v acetonitrile, 1% v/v ethanol,1%v/v methanol, 1e50% v/v tert-butyl methyl ether) or ChCl:Gly(1:2 mol/mol) was added. In any case, the final volume of the reactionwas adjusted up to 0.5 mL in a 2 mL eppendorf tube. |
94 % ee | With oxygen |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | Stage #1: methylphenylsulfonate With n-butyllithium In tetrahydrofuran; hexane at -72℃; for 0.5h; Stage #2: tert-butyl (S)-N-tert-butoxycarbonylpyroglutamate In tetrahydrofuran; hexane at -72℃; for 1.75h; | |
95% | With n-butyllithium In tetrahydrofuran; hexane at -72℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | Stage #1: methylphenylsulfonate With n-butyllithium In tetrahydrofuran; hexane at -15℃; for 0.5h; Stage #2: ethyl 6-heptenoate In tetrahydrofuran; hexane at -78 - 22℃; | |
92% | Stage #1: methylphenylsulfonate With n-butyllithium In tetrahydrofuran; hexane at -15℃; for 0.5h; Stage #2: ethyl 6-heptenoate In tetrahydrofuran; hexane at -78 - 20℃; | 38 Example 38 β-Ketosulfone 57: To a solution of methyl phenyl sulfone (1.43 g, 9.14 mmol) in THF (15 ML) AT-15 °C WAS added BuLi (6.28 mL, 10.0 mmol, 1.6M in hexane). After stirring for 30 min, the reaction mixture was cooled to -78 °C and ethyl 6-HEPTENOATE (802 PL, 4.57 mmol) was added. The reaction mixture was warmed to rt and then treated with saturated aqueous NH4Cl solution. The organic layer was separated and the aqueous layer was extracted with EtOAc (3x). The combined organic layers were dried (MGS04) and concentrated under reduced pressure. Purification of the crude product by FC (hexane/EtOAc 5: 1) afforded β-KETOSULFONE 57 (1.12 g, 92%) as a white solid. 1H-NMR (500 MHz, CDC13) 67. 88- 7. 86 (M, 2H), 7. 68-7. 65 (M, 1H), 7. 58-7. 54 (m, 2H), 5. 79-5. 71 (m, 1H), 5.00-4. 92 (m, 2EI), 4.14 (s, 2H), 2.70-2. 67 (m, 2H), 2.05-2. 00 (m, 2H), 1.58-1. 52 (M, 2H), 1.38-1. 32 (M, 2H); 13C-NMR (125 MHz, CDC13) 6197. 99, 138. 14,134. 19,129. 25, 129.06, 128.17, 114.73, 66.70, 44.12, 33.26, 27.85, 22.42 ; MS (ESI) 289 [M+NAL ; HRMS (FAB) calcd. for C14H18O3SNa [M+Na+] 289.0874, found 289.0882. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With n-butyllithium In tetrahydrofuran at 0℃; for 0.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 90% 2: 8 % Spectr. | With dihydrogen peroxide at 20℃; for 3h; | |
1: 62% 2: 25% | With tert.-butylhydroperoxide In tetrachloromethane; water at 20℃; for 18h; optical yield given as %ee; enantioselective reaction; | |
With Cumene hydroperoxide; chiral cyclohexyl-1,2-bis-hydroxamic acid-based reagent In dichloromethane at -40 - 0℃; for 43h; |
With Cumene hydroperoxide In dichloromethane at -40 - 0℃; for 43h; | ||
1: 90 % Spectr. 2: 9 % Spectr. | With phosphate buffer; dihydrogen peroxide In methanol at 20℃; for 24h; | |
1: 96 %Spectr. 2: 4 %Spectr. | With C62H52ClFeN2O2; dihydrogen peroxide In water at 0℃; for 6h; optical yield given as %ee; enantioselective reaction; | |
With C16H12O8W(2-)*C32H68P(1+); urea hydrogen peroxide adduct In dichloromethane at 20℃; for 1h; optical yield given as %ee; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With silver(I) acetate; potassium carbonate In 1-methyl-pyrrolidin-2-one at 120℃; for 16h; Inert atmosphere; | |
70% | With copper(I) oxide; 1,10-Phenanthroline In 1-methyl-pyrrolidin-2-one; quinoline at 190℃; for 0.0833333h; Microwave irradiation; | |
54% | In quinoline at 170℃; for 6h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With 1,10-Phenanthroline; 4 A molecular sieve; oxygen In dichloromethane; dimethyl sulfoxide at 40℃; for 72h; atmospheric pressure; | |
68% | With copper diacetate; 1-(n-butyl)-3-methylimidazolium triflate at 20℃; for 12h; | |
64% | With 1-benzylimidazole; copper diacetate; potassium carbonate In dimethyl sulfoxide at 60℃; for 22h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 79 percent Chromat. / HCOONH4 / Ru3(CO)12 / dioxane / 20 h / 160 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | at 105℃; for 8h; | 4 EXAMPLE 4; Methanesulfonylation of Other ArH Compounds ArH gives ArSO2Me [0295] Molar proportion of catalyst with respect to the substrate 10% The combinations of the triflic with the following metal chlorides have also been tested positively: antimony(III) chloride, antimony(V) chloride, tin(IV) chloride and tin(IV) chloride pentahydrate. [0297] Furthermore, the combinations of the triflic with bismuth oxychloride and bismuth oxide are active. [0298] Finally, the use of triflic monohydrate also results in active systems, which has been demonstrated in the case of the system with gallium chloride. From the latter position, it could be inferred therefrom that the use of a vigorously anhydrous medium is not necessary. |
31% | at 105℃; for 8h; | 4 EXAMPLE 4; Methanesulfonylation of Other ArH Compounds ArH gives ArSO2Me [0295] Molar proportion of catalyst with respect to the substrate 10% The combinations of the triflic with the following metal chlorides have also been tested positively: antimony(III) chloride, antimony(V) chloride, tin(IV) chloride and tin(IV) chloride pentahydrate. [0297] Furthermore, the combinations of the triflic with bismuth oxychloride and bismuth oxide are active. [0298] Finally, the use of triflic monohydrate also results in active systems, which has been demonstrated in the case of the system with gallium chloride. From the latter position, it could be inferred therefrom that the use of a vigorously anhydrous medium is not necessary. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In tetrahydrofuran; ice-water; dimethyl sulfoxide; | EXAMPLE 3 Under nitrogen, 3 g of a 55% strength dispersion of sodium hydride, which has been washed with pentane, are suspended in 30 ml of dimethylsulphoxide. After adding 9.3 g of methylphenylsulphone, the mixture is warmed to 60. After the evolution of hydrogen has ceased, the mixture is cooled to 0, diluted with 50 ml of tetrahydrofurane and, at this temperature, a solution of 4 g of <strong>[55150-07-7]methyl N-methyl-5-chloro-anthranilate</strong> in 20 ml of tetrahydrofurane is added dropwise in the course of about 20 minutes. The mixture is stirred overnight at room temperature and then poured into about 200 ml of ice-water. The resulting mixture is acidified with 2 N hydrochloric acid and stirred for a further 1 hour. The oily precipitate crystallises slowly. It is filtered off with suction and recrystallized from chloroform/ethanol. 2'-N-Methylamino-5'-chloro-2-(phenylsulphonyl)-acetophenone with a melting point of 160-162 is obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With sulfuric acid; sulfur trioxide; nitric acid at 0 - 140℃; for 6h; | Methylphenylsulfone (5.0 g; 32 mmol) was added to an ice cold solution of 10 mL of fuming HNO3 and 65%oleum. The mixture was slowly heated to 140 C and stirred for 6 hours. After cooling to room temperature, the mixturewas poured onto ice and the precipitate filtered and washed with diisopropylether. 5.5 g (22.3 mmol; 70% yield) of 1-methylsulfonyl-3,5-dinitro-benzene were obtained as a colorless solid . |
25.6% | With sulfuric acid; nitric acid at 140℃; for 16h; Cooling with ice; | 7 Preparation 7 3,5-dinitrophenyl methyl sulfone To an ice-bath cooled solution of nitric acid(90%) (20 mL) and fuming sulfuric acid (40 mL) was slowly added (methylsulfonyl)benzene (10. Og, 64.0 mmol) in 4 portions. The ice- bath was removed then the reaction mixture was slowly heated to 140 deg C in an oil bath for 16 h. The reaction mixture was cooled to rt then slowly poured over solid ice while swirling. The solid was collected by filtration then washed with water (300 ml), ethanol (80 mL) and ethylether (100 mL). The solid was suspended and stirred in DMSO (40 mL) for 5-10 min then filtered. The solid was washed successively with water, ethanol, then ethyl ether to give the title compound as a white solid (4.04 g, 25.6%). 1 H NMR (DMSO-d6) δ: 9.10 (t, 1 H), 9.02 (d, J = 2.0 Hz, 2H), 3.51 (s, 3H), MS (m/z) 247.1 (M+H+). |
25.6% | With sulfuric acid; nitric acid at 140℃; for 16h; Cooling with ice; | 2 Preparation 2 3,5-dinitrophenyl methyl sulfone To an ice-bath cooled solution of nitric acid(90%) (20 mL) and fuming sulfuric acid (40 mL) was slowly added (methylsulfonyl)benzene (10.0g, 64.0 mmol) in 4 portions. The ice-bath was removed then the reaction mixture was slowly heated to 140 deg C in an oil bath for 16 h. The reaction mixture was cooled to rt then slowly poured over solid ice while swirling. The solid was collected by filtration then washed with water (300 ml), ethanol (80 mL) and ethylether (100 mL). The solid was suspended and stirred in DMSO (40 mL) for 5-10 min then filtered. The solid was washed successively with water, ethanol, then ethyl ether to give the title compound as a white solid (4.04 g, 25.6%). 1H NMR (DMSO-de) δ 9.10 (t, 1 H), 9.02 (d, J = 2.0 Hz, 2H), 3.51 (s, 3H); MS (m/z) 247.1 (M+H+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
25% | Stage #1: methylphenylsulfonate With n-butyllithium In tetrahydrofuran at 0℃; for 0.5h; Stage #2: L-N3-Nle-OMe In tetrahydrofuran at -78℃; for 3h; Further stages.; | |
25% | Stage #1: methylphenylsulfonate With n-butyllithium In tetrahydrofuran at 0℃; for 0.5h; Stage #2: L-N3-Nle-OMe In tetrahydrofuran at -78℃; for 3h; | 1 THF β-Keto sulfone 45[0148] This procedure was adapted from Chun. Chun, J.; Li, G.; Byun, H. -S.; Bittman, R. J. Org. Chem. 2002, 67, 2600-2605. To a 0.6 M solution of methyl phenyl sulfone (1.30 g, 8.31 mmol) in THF (14 raL) at 0 0C was added dropwise n-butyllithium (7.55 mL, 16.6 mmol). The reaction mixture was stirred at 0 0C for 30 min and then cooled to -78 0C. A 0.6 M solution of methyl ester 44 (0.711 g, 4.15 mmol) in THF (6.9 mL) was added dropwise. The reaction mixture was stirred at -78 0C for 3 h. Saturated aqueous NH4Cl (10 mL) was added and the product was extracted with EtOAc (3 x 20 mL). The organic layers were combined, washed with saturated NaCl, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude reaction mixture was purified by column chromatography (5- 25% EtOAc/hexanes) to afford 0.300 g (25%) of 45 as a pale yellow solid, mp 64-66 0C. IR Vmax (cm"1): 2959, 2935, 2873, 2104, 1728, 1321, 1 155. 1H NMR (300 MHz, CDCl3): δ 0.91 (t, 3H, J= 7.2), 1.28-1.46 (m, 4H), 1.52-1.90 (m, 2H), 4.13 (dd, IH, J= 4.8, 8.4), 4.26 (d, IH, J= 13.8), 4.42 (d, IH, J= 13.8), 7.56-7.64 (m, 2H), 7.68-7.75 (m, IH), 7.88-7.93 (m, 2H). 13C-NMR (125 MHz, CDCl3): δ 14.0, 22.4, 27.9, 29.9, 63.7, 68.6, 128.6, 129.6, 134.7, 138.7, 195.5. HRMS-FAB (m/z): [MLi]+ calcd for Ci3HnN3O3SLi, 302.1151; found, 302.1142 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: methylphenylsulfonate With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.25h; Stage #2: methyl pyridine-2-carboxylate In tetrahydrofuran at -78 - 20℃; | 100 Example 100; (Phenylsulphonylmethyl)-(pyrid-2-yl)-ketone A solution of methylphenyl sulphone (3g, 19. [2MMOL)] in THF was added dropwise to a solution of lithium diisopropyl amine (2. [7ML] diisopropylamine and [12ML] of 1.6M n-butyl lithium) in THF under argon [AT-78°C.] The resultant pink-orange solution was stirred at-78°C for 15 mins. A solution of pyridine 2-methylcarboxylate (1.32g, 9. [6MMOL)] in THF was added. The reaction mixture was stirred at-78°C for 2 hours, then allowed to warm to room temperature and was stirred overnight. The reaction was quenched with water, filtered and evaporated to dryness to give an oil. This oil was taken up in EtOAc and purified with flash chromatography (2: 1 EtOAc: petrol) to give the product which was recrystallized from EtOAc/petrol to give the solid (840mg). Mp [101-103°C] ; m/z 261 (M+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.25h; | |
87% | Stage #1: methylphenylsulfonate With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.166667h; Inert atmosphere; Stage #2: 1-[chloro(p-tolylsulfinyl)methylidene]cyclobutane In tetrahydrofuran at -78℃; for 0.25h; Inert atmosphere; Stage #3: With ammonium chloride In tetrahydrofuran; water | 3.1.60. {1-[Chloro(p-tolylsulfinyl)methyl]cyclobutyl}methyl phenyl sulfone (43c) General procedure: tert-Butyl acetate (0.14 mL; 1.0 mmol) was added to a solution of LDA (1.0 mmol) in 3 mL of dry THF at -78 °C under argon atmosphere with stirring. After the solution was stirred for 10 min, a solution of vinyl sulfoxide 8 (71 mg; 0.2 mmol) in THF (1 mL) was added. The reaction mixture was stirred for 15 min and then reaction was quenched by adding saturated aq. NH4Cl. The whole mixture was extracted with CHCl3. The product was purified by silica gel column chromatography to afford adduct 9 (94 mg; 99%) as colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 19; Comparative Preparation of Acetyl EPSIP According to Example 1 of WO 2005/007649(a) (R)-5-Bromo-3-(N-methylpyrrolidine-2-ylmethyl)-1H-indole (100 g), acetonitrile (147 mL), TEA (44.92 g) and acetic anhydride (44.92 g) were charged to a dry glass lined vessel. The resulting mixture was heated to reflux and maintained at this temperature for 4.5 hours.(b) A mixture of acetonitrile (147 mL), palladium acetate (4.88 g) and tri-o-tolylphosphine (23.4 g) was stirred for 1 hour. Phenyl vinyl sulphone (62.5 g), TEA (35.93 g) and the solution prepared in part (a) were added and the resulting mixture was heated to reflux for 7.5 hours. The reaction mixture was cooled and a solution of 74.2 g of concentrated HCl in 469 mL water was added over 4 hours. The resulting mixture was filtered to remove spent catalyst. Water (1172 mL) and 117.1 mL of 50% w/w aqueous sodium hydroxide solution were added to the filtrate to produce a sticky mass. The product did not precipitate after 4.5 hours. The reaction mixture was stirred for 14-16 hour, after which the product was still not precipitated. The water was decanted to provide the crude (R)-1-acetyl-5-(2-phenylsulphonylethenyl)-3-(N-methylpyrrolidin-2-ylmethyl)-1H-indole) as a dark brown, sticky mass. This crude sticky product was added to 207 g of acetone. This mixture was heated to 60 C. On reaching this temperature 317 g of water was added over 2 hours whilst simultaneously cooling the mixture to ambient temperature. The batch was then granulated for 2 hours. The product did not solidify, and the dark brown sticky mass was still observed after 16 hours of stirring.(R)-1-acetyl-5-(2-phenylsulphonylethenyl)-3-(N-methylpyrrolidin-2-ylmethyl)-1H-indole (?Acetyl EPSIP?): 58.32% (RT=117.29); (Methylsulfonyl)benzene (?EPS?): 10.47% (RT=7.26); tri-O-tolyl phosphine (?TOTP?): 17.98% (RT=32.19); 1,2-bis(phenylsulfonyl)ethane) (?EPS?) Dimer: 1.0% (RT=19.85); 3-[(R)-1-methyl-pyrrolidin-2-ylmethyl]-1H-indole (Des bromo BIP) (?DBBIP?): 0.81% (RT=5.13). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With N-(dicyclohexylphosphino)-2-(2'-methylphenyl)-1H-indole; palladium diacetate; lithium tert-butoxide In toluene at 110℃; for 12h; Inert atmosphere; | |
86% | With palladium diacetate; lithium tert-butoxide; XPhos at 120℃; for 12h; Inert atmosphere; | |
85% | Stage #1: methylphenylsulfonate With lithium hexamethyldisilazane In tetrahydrofuran at -20 - 20℃; Inert atmosphere; Stage #2: With zinc(II) chloride In tetrahydrofuran at -20 - 20℃; for 1h; Inert atmosphere; Stage #3: bromobenzene With palladium diacetate; XPhos In tetrahydrofuran at 65℃; Degassed under vacuum; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
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82% | To a solution of (methylsulfonyl)benzene (2.2 g, 13.9 mmol) in THF (38 mL) at 0 was added n-BuLi (2.5 M in hexanes, 12.2 mL, 30.6 mmol) dropwise over 10 minutes. After the mixture was stirred for 30 min, chlorodiethylphosphonate (2.4 mL, 16.7 mmol) was added dropwise to the reaction. After 30 minutes, a solution of oxetan-3-one (1.0 g, 13.9 mmol) in THF (2 mL) was added dropwise to the reaction mixture at -78 . The reaction mixture was stirred at -78 for 2 hours, then diluted with aqueous NH4Cl (100 mL) and extracted with EtOAc (100 mL x 2) . The combined organic layers were concentrated and the residue was purified by silica gel chromatxography column (petroleum ether/EtOAc = 3/1) to give the title compound (2.4 g, 82%) as a colorless oil. 1H NMR (400 MHz, CDCl3) : delta7.90-7.88 (m, 2H) , 7.68-7.64 (m, 1H) , 7.57 (t, J= 7.6 Hz, 2H) , 6.13-6.11 (m, 1H) , 5.66-5.64 (m, 2H) , 5.30-5.27 (m, 2H). | |
75% | 3-((Phenylsulfonyl)methylene)oxetane To an oven-dried vial was added (methylsulfonyl)benzene (0.570 g, 3.65 mmol) and the vial was evacuated with argon 3 times. The dry THF (17 mL) was added and the reaction was cooled to 0 C. The 2.5 M BuLi in hexanes (3.21 mL, 8.03 mmol) was added dropwise and the reaction began to stir at 0 C. and stirred for 45 minutes. The diethyl chlorophosphate (0.528 mL, 3.65 mmol) was then added at 0 C. and the reaction stirred for 30 minutes. The reaction was then cooled to -78 C. and the oxetan-3-one (0.330 mL, 5.15 mmol) was then added dropwise and the reaction stirred for 2 h. The reaction was then warmed to rt and filtered through a silica plug. The reaction was then concentrated onto silica and purified by MPLC (20 min, 0-40% EtOAc:hex) to provide pure 3-((phenylsulfonyl)methylene)oxetane (0.579 g, 2.75 mmol, 75% yield). 1H NMR (400 MHz, CDCl3): delta 7.91-7.87 (m, 2H), 7.69-7.64 (m, 1H), 7.60-7.55 (m, 2H), 6.12 (quintet, J=2.3 Hz, 1H), 5.66-5.63 (m, 2H), 5.30-5.27 (m, 2H). | |
74% | To a stirred solution of methyiphenylsulfone (3 g, 19.2 mmol) in dry tetrahydrofuran (15 mL) was added n-butyllithium (2.5 M in tetrahydrofuran; 15.4 mL, 38.4 mmol) at 0 C. Thereaction mixture was stirred for 30 mi Diethyl chiorophosphate (4 mL, 27.8 mmol) wasadded, and the mixture was stirred at 0 C for an additional 30 mm. It was then cooled to -78C, and a solution of 3-oxetanone (1.38 g, 19.2 mmol) in dry tetrahydrofuran (3 mL) wasadded. The mixture was stirred at -78 C for 1.5 h and filtered through a silica plug to give 3-((phenylsulfonyl)methylene)oxetane as a white solid (3 g, 74%). ?H NMR (400 MHz, CDC13)oe 7.90 - 7.87 (m, 2H), 7.66 - 7.64 (m, 1H), 7.59 - 7.56 (m, 2H), 6.12 (s, 1H), 5.65 (d, J =6.0Hz, 2H), 5.29 (d, J =5.6 Hz, 2H). |
Example 1313-A. 3-((Phenylsulfonyl)methylene)oxetane.A solution of BuLi (2.5 M in hexanes, 22.5 mL, 56.3 mmol) was added over 10 min to a solution of methylphenylsulfone (4.00 g, 25.6 mmol) in THF (70 mL) at 0 C. The solution went from clear to light green to a heterogeneous yellow suspension. The mixture was stirred for 30 min at 0 C and then chlorodiethylphosphonate (4.46 mL, 30.7 mmol) was added dropwise and the stirring was continued for 30 min, at which point the solution turned clear orange. The reaction mixture was then cooled to -78 C and oxetan-3-one (1.85 g, 25.6 mmol) was added in THF (3 mL). The reaction mixture turned pale brown/yellow in color. After stirring for another 1.5 h, the reaction mixture was filtered through a plug of silica gel. The filtrate was triturated with solid NH4C1 until pH reached 7. The mixture was then filtered and the filtrate was concentrated. The residue was purified by silica gel chromatography (0-60%EtOAc/heptane) to provide 3-((phenylsulfonyl)methylene)oxetane. 1H NMR (400 MHz, CD2C12) delta ppm 7.86 - 7.99 (m, 2 H) 7.68 - 7.77 (m, 1 H) 7.57 - 7.68 (m, 2 H) 6.18 (t, J=2.40 Hz, 1 H) 5.59 - 5.70 (m, 2 H) 5.30 (td, J=3.41, 2.27 Hz, 2 H) | ||
Example 34 Preparation of 3-(phenylsulfonylmethylene)oxetane [0275] In a dry 100 mL flask, methylsulfonylbenzene (1.00 g, 6.41 mmoles) in a solution of dry tetrahydrofuran was 2.5 M n-buLi added at 0C over 10 mins then stirred for 30 mins. Chlorodiethylphosphonate (1.1 mL) was added dropwise and continued to stir for 30 mins before cooling to -78C. Oxetan-3-one (0.65 g, 9.04 mmoles) in dry diethylether (1.0 mL) was added and stirred for 1.5h. The reaction was filtered through a silica plug and to get pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | Stage #1: methylphenylsulfonate With n-butyllithium In tetrahydrofuran; hexane at 0℃; for 1h; Inert atmosphere; Stage #2: ethyl 3-(1-(2-(tert-butyldiphenylsilyloxy)ethyl)cyclohexa-2,5-dienyl)propanoate In tetrahydrofuran; hexane at 0℃; for 0.5h; Inert atmosphere; | 4.2.8. 4-(1-(2-(tert-Butyldiphenylsilyloxy)ethyl)cyclohexa-2,5-dienyl)-1-(phenylsulfonyl)butan-2-one (17c) To a stirred solution of methyl phenyl sulfone (38.4 mg, 0.247 mmol) in THF (2 mL) was added n-BuLi (1.66 M in hexane, 0.296 mL, 0.494 mmol) at 0 °C and the solution was stirred at this temperature for 1 h. Then, to the reaction mixture was added a solution of 17b (104 mg, 0.225 mmol) in THF (1 mL) via a cannula and the mixture was stirred at this temperature for 30 min. The reaction was quenched with saturated aqueous NH4Cl (5 mL), and the aqueous layer was extracted with Et2O (5 mL×2). The combined organic layer was dried over Na2SO4, filtered, and evaporated. The residue was purified by flash column chromatography (hexane/ethyl acetate=4/1) to afford saturated ester 17c (121 mg, 95%) as a colorless oil; Rf 0.26 (hexane/ethyl acetate=4/1); 1H NMR (400 MHz, CDCl3) δ 7.87-7.85 (2H, m), 7.69-7.62 (5H, m), 7.58-7.54 (2H, m), 7.43-7.34 (6H, m), 5.68 (2H, ddd, J=10.2, 3.2, 3.2 Hz), 5.11 (2H, d, J=10.2 Hz), 4.09 (2H, s), 3.59 (2H, t, J=7.1 Hz), 2.50 (2H, t, J=7.8 Hz), 2.50-2.45 (2H, m), 1.61 (2H, t, J=7.8 Hz), 1.52 (2H, t, J=7.1 Hz), 1.01 (9H, s); 13C NMR (100 MHz, CDCl3) δ 198.7, 138.8, 135.6, 134.2, 134.0, 131.1, 129.5, 129.3, 128.3, 127.5, 125.6, 66.9, 61.3, 44,5, 40.4, 38.4, 34.9, 26.8, 19.1; IR (neat) νmax 2931, 2856, 1720, 1587, 1524, 1155, 1111, 1085, 823, 742, 704 cm-1; FAB HRMS [M+Na]+ calcd for C34H40O4SiSNa: 595.2314, found: 595.2291. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | Stage #1: methylphenylsulfonate With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.166667h; Inert atmosphere; Stage #2: (E)-4-methoxymethoxybut-2-enal In tetrahydrofuran; hexane at -78℃; for 1h; Inert atmosphere; Stage #3: With water; ammonium chloride In tetrahydrofuran; hexane | 4.2.3. Addition of methylphenylsulfone to 2: (E)-5-(methoxymethoxy)-1-(phenylsulfonyl)pent-3-en-2-ol, 2a Methylphenylsulfone (3.27 g, 20.9 mmol) was dissolved in 190 ml of THF under Ar at -78 °C. n-BuLi (1.6 M in hexanes, 13 ml, 20.9 mmol) was added and the mixture was stirred 10 min. Separately, 2 (3.02 g, 23.23 mmol) was dissolved in 42 ml of THF under Ar at rt. This solution was added via cannula to the former one and the mixture was stirred at -78 °C under Ar for 1 h. Then the reaction was quenched with a NH4Cl saturated solution and extracted with EtOAc. The combined organics were washed with H2O, dried (Na2SO4), filtered and concentrated in vacuo to leave a crude yellow oil. Flash chromatography (hexane/EtOAc, 7/3) afforded 2a (3.75 g, 63%). νmax (liquid film) 3457, 2932, 2884, 1305, 1145, 1086, 1041; δH (200 MHz; CDCl3) 7.92 (2H, dd, J=8.2, 1.4 Hz, ArHortho), 7.73-7.48 (3H, m, ArHmeta, ArHpara), 5.86 (1H, dt, J=14.0, 6.0 Hz, H4), 5.64 (1H, dd, J=14.0, 4.0 Hz, H3), 4.70 (1H, m, H2), 4.58 (2H, s, O-CH2-O), 3.99 (2H, d, J=6.0 Hz, H5), 3.31 (3H, s, O-CH3), 3.25 (2H, m, H1); δC (50 MHz; CDCl3) 139.5, 134.3, 131.2, 129.7 (2C), 129.0, 128.2(2C), 96.0, 66.5, 62.1, 55.5; EIHRMS: calcd for C13H18O5S(M+Na): 309.0773; found: 309.0767 (M+Na). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Step A: Preparation of 6-(phenylsulfonyl)-2-oxaspiror3.31heptane: To a solution of methylsulfonylbenzene (2.00 g; 12.8 mmol) in dry THF (40 mL) under nitrogen at 0 C was added butyl lithium (25.6 mmol; 2.5M solution on hexane). The mixture was stirred for 1 hour and then cooled to -20 C. Tetramethylethylenediamine (1.93 mL; 12.8 mmol) was added followed by a solution of <strong>[78-71-7]3,3-bis(chloromethyl)oxetane</strong> (1.98 g; 12.8 mmol) in dry THF (10 mL). The mixture was allowed to warm to 0 C and then slowly allowed to reach 15 C over 12 hours. Water (100 mL) was added and the mixture was extracted into ethyl acetate (4 x 50 mL). The combined extracts were dried over sodium sulfate, filtered and concentrated under reduced pressure. The material was purified on silica gel (Biotage system, utilizing two 120 g columns in series) eluting with hexane/ethyl acetate (2: 1 to 1 :2 gradient). The desired product was obtained as an off white solid (700 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With triethylsilane; chloro-trimethyl-silane; palladium dichloride In tetrahydrofuran at 20℃; for 0.25h; Inert atmosphere; | General procedure for the reductive cleavage of alkyl aryl sulfides General procedure: To a solution of aryl alkyl sulfide (0.23 mmol, 1.0 equiv) and PdCl2 (0.007 mmol, 3 mol %, 1.2 mg) in 2 mL of THF was added triethylsilane (amount indicated in Table 3) under argon atmosphere (color of the reaction mixture turned to black). The resulting mixture was stirred at room temperature (or at the indicated temperature in Table 3). After completion of the reaction, to the reaction mixture was added 4 mL of H2O (gas evolves). The aqueous layer was extracted with CH2Cl2 (4 mL × 2), and the combined organic layer was dried over Na2SO4 and evaporated. The residue was purified by silica gel column chromatography using hexane/ethyl acetate as eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | Stage #1: methylphenylsulfonate With n-butyllithium In tetrahydrofuran; hexane at -78 - 20℃; for 4h; Inert atmosphere; Schlenk technique; Stage #2: chloro-diphenylphosphine In tetrahydrofuran; hexane at -78 - 20℃; for 16h; Inert atmosphere; Schlenk technique; Stage #3: With oxygen | |
61% | Stage #1: methylphenylsulfonate With n-butyllithium In tetrahydrofuran; hexane at 0℃; for 0.5h; Inert atmosphere; Schlenk technique; Stage #2: With triisobutylaluminum In tetrahydrofuran; hexane; toluene for 0.5h; Inert atmosphere; Schlenk technique; Stage #3: chloro-diphenylphosphine In tetrahydrofuran; hexane; toluene at 0 - 20℃; for 2h; Inert atmosphere; Schlenk technique; | Synthesis of compound 3 The synthesis of 3 was achieved with an adapted procedure reported by Imamoto etal. [10] Methyl phenyl sulfone (2.00g, 12.8mmol) was dissolved in 40ml THF and the solution cooled to 0°C. nBuLi (5.74ml, 12.8mmol, 2.23M in hexane) was slowly added in the course of 30min. The resulting solution was stirred for 30min. Al(iBu)3 (11.6ml, 12.8mmol, 1.1M in toluene) was added over 30min. The reaction mixture was stirred for additional 30min and subsequently slowly added to a solution of ClPPh2 (3.67g, 16.64mmol) in 40ml THF at 0°C. The reaction mixture was stirred for 1h at 0°C and 1h at room temperature. 100mlH2O were carefully added, the phases separated, and the aqueous phase extracted two times with 50ml CHCl3. The organic phases were combined, dried over Na2SO4, filtrated and the solvent evaporated. The residue was dissolved in 50ml THF and an excess H2O2 was added. The mixture was stirred overnight. 30mlH2O were added, the phases separated, and the aqueous phase extracted three times with DCM (50ml). The organic phases were combined, dried over Na2SO4, filtrated and the solvent removed in vacuo. The resulting solid was recrystallized from hot EtOH (85ml) to afford 2.77g (7.81mmol, 61%) of 3 as colorless needles. 1H NMR: (400.1MHz, CDCl3): δ=4.28 (d, 2JHP=10.0Hz, 2H; SCH2P), 7.45-7.61 (m, 9H; CHSPh,meta,para+CHPPh,meta,para), 7.73-7.78 (m, 4H; CHPPh,ortho), 7.87-7.89 (m, 2H; CHSPPh,ortho).31P{1H}-NMR: (162.0MHz, CDCl3): δ=20.2. Further spectroscopic data are in accordance with the literature [7a]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With chlorosulfonic acid In chlorosulfonic acid at 90℃; for 18h; | 2 3-Methanesulfonylbenzene-1-sulfonyl chloride 3-Methanesulfonylbenzene-1-sulfonyl chloride The intermediate 3-methanesulfonylbenzene-1-sulfonyl chloride was synthesized according to the methods disclosed in Park et al., J. Med. Chem. 51(21):6902-6915 (2008). Specifically, methyl sulfonyl benzene (110 g, 0.7 mol) was heated for 18 hours at 90° C. in chlorosulfonic acid (450 mL, 6.7 mol) after which time the reaction mixture was allowed to cool to a temperature of about 21° C. before slowly being poured onto crushed ice. The resulting slurry was twice extracted into EtOAc (2 L for each extraction). The organic portions were combined and washed with brine (50 mL) before being dried over sodium sulfate, filtered and concentrated under reduced pressure to provide the intermediate sulfonyl chloride as an off white solid (125 g, yield 75%). 1H NMR (400 MHz, CDCl3) δ ppm 8.61 (1 h, t, J=1.7 Hz), 8.35-8.31 (2H, m), 7.90 (1H, t, J=7.9 Hz), 3.15 (3H, s). |
6.1% | In chlorosulfonic acid at 90℃; for 18h; | 16.1 Step 1 Methylsulfonylbenzene (5 g, 32 mmol) was placed into chlorosulfonic acid (37 g, 320 mmol), heated at 90 °Cfor 18 h, and cooled to room temperature. The mixture was slowly poured into crushed ice. The resulting suspensionwas extracted with ethyl acetate (2 3 200 mL). The organic layers were separated, combined, washed with saturatedaqueous NaCl solution (50 mL), and dried with sodium sulfate. After suction filtration, the resulting filtrate was distilledunder reduced pressure. The residue was the intermediate 3-methylsulfonylphenyl-1-sulfonyl chloride (50 mg, yield6.1%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With aluminum (III) chloride at 200℃; for 3h; Inert atmosphere; | Thermal-Catalyzed Reaction ofAcids 1 with (Phenylsulfonyl)acetonitrile; General Procedure 2 (GP2) General procedure: In a 10 mL round-bottomed flask, (phenylsulfonyl)acetonitrile (544mg, 3.0 mmol, 1.0 equiv) was added to a mixture of acid 1(3.0mmol) and AlCl3(8 mg, 0.06 mmol, 0.02 equiv). The mixture was then stirred under argon at 200 °C for 3 h. After completion of the reaction, the crude mixture was diluted with CH2Cl2(5 mL + 5 mL),silica gel (3 g) was then added to make a solid deposit after evaporation of the solvent. A silica gel column chromatography (eluent:PE-EtOAc, 95:5) finally afforded the pure nitrile together with methyl phenyl sulfone. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With aluminum (III) chloride; at 200℃; for 3h;Inert atmosphere; | General procedure: In a 10 mL round-bottomed flask, (phenylsulfonyl)acetonitrile (544mg, 3.0 mmol, 1.0 equiv) was added to a mixture of acid 1(3.0mmol) and AlCl3(8 mg, 0.06 mmol, 0.02 equiv). The mixture was then stirred under argon at 200 C for 3 h. After completion of the reaction, the crude mixture was diluted with CH2Cl2(5 mL + 5 mL),silica gel (3 g) was then added to make a solid deposit after evaporation of the solvent. A silica gel column chromatography (eluent:PE-EtOAc, 95:5) finally afforded the pure nitrile together with methyl phenyl sulfone. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With aluminum (III) chloride; at 200℃; for 3h;Inert atmosphere; | General procedure: In a 10 mL round-bottomed flask, (phenylsulfonyl)acetonitrile (544mg, 3.0 mmol, 1.0 equiv) was added to a mixture of acid 1(3.0mmol) and AlCl3(8 mg, 0.06 mmol, 0.02 equiv). The mixture was then stirred under argon at 200 C for 3 h. After completion of the reaction, the crude mixture was diluted with CH2Cl2(5 mL + 5 mL),silica gel (3 g) was then added to make a solid deposit after evaporation of the solvent. A silica gel column chromatography (eluent:PE-EtOAc, 95:5) finally afforded the pure nitrile together with methyl phenyl sulfone. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate; 1-Adamantanecarboxylic acid In chlorobenzene at 140℃; for 24h; Inert atmosphere; regioselective reaction; | 4.6. Reaction of methyl phenyl sulfones 1 with alkynes 2 General procedure: To a 20 mL two-necked flask with a reflux condenser, a balloon,and a rubber cup were added methyl phenyl sulfone 1 (0.75 mmol),alkyne 2 (0.25 mmol), [Cp*Rh(MeCN)3](SbF6)2 (0.01 mmol, 8.3 mg),1-AdCOOH (0.1 mmol, 18 mg), 1-methylnaphlene (ca. 30 mg) as internal standard, and PhCl (1 mL). Then, the resulting mixture was stirred under nitrogen at 140 C for 24 h. After cooling, the reaction mixture was extracted with ethyl acetate (100 mL). The organic layer was washed by aqueous NaHCO3 (100 mL, three times) and dried over Na2SO4. After evaporation of the solvents under vacuum,product 3 was isolated by column chromatography on silica gel using hexane/ethyl acetate as eluent. Further purification by gel permeation chromatography (GPC) was performed, if needed. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate; 1-Adamantanecarboxylic acid; In chlorobenzene; at 140℃; for 24h;Inert atmosphere; | General procedure: To a 20 mL two-necked flask with a reflux condenser, a balloon,and a rubber cup were added methyl phenyl sulfone 1 (0.75 mmol),alkyne 2 (0.25 mmol), [Cp*Rh(MeCN)3](SbF6)2 (0.01 mmol, 8.3 mg),1-AdCOOH (0.1 mmol, 18 mg), 1-methylnaphlene (ca. 30 mg) as internal standard, and PhCl (1 mL). Then, the resulting mixture was stirred under nitrogen at 140 C for 24 h. After cooling, the reaction mixture was extracted with ethyl acetate (100 mL). The organic layer was washed by aqueous NaHCO3 (100 mL, three times) and dried over Na2SO4. After evaporation of the solvents under vacuum,product 3 was isolated by column chromatography on silica gel using hexane/ethyl acetate as eluent. Further purification by gel permeation chromatography (GPC) was performed, if needed. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46% | With tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate; 1-Adamantanecarboxylic acid In chlorobenzene at 140℃; for 24h; Inert atmosphere; regioselective reaction; | 4.6. Reaction of methyl phenyl sulfones 1 with alkynes 2 General procedure: To a 20 mL two-necked flask with a reflux condenser, a balloon,and a rubber cup were added methyl phenyl sulfone 1 (0.75 mmol),alkyne 2 (0.25 mmol), [Cp*Rh(MeCN)3](SbF6)2 (0.01 mmol, 8.3 mg),1-AdCOOH (0.1 mmol, 18 mg), 1-methylnaphlene (ca. 30 mg) as internal standard, and PhCl (1 mL). Then, the resulting mixture was stirred under nitrogen at 140 C for 24 h. After cooling, the reaction mixture was extracted with ethyl acetate (100 mL). The organic layer was washed by aqueous NaHCO3 (100 mL, three times) and dried over Na2SO4. After evaporation of the solvents under vacuum,product 3 was isolated by column chromatography on silica gel using hexane/ethyl acetate as eluent. Further purification by gel permeation chromatography (GPC) was performed, if needed. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47% | With tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate; 1-Adamantanecarboxylic acid In chlorobenzene at 140℃; for 24h; Inert atmosphere; regioselective reaction; | 4.6. Reaction of methyl phenyl sulfones 1 with alkynes 2 General procedure: To a 20 mL two-necked flask with a reflux condenser, a balloon,and a rubber cup were added methyl phenyl sulfone 1 (0.75 mmol),alkyne 2 (0.25 mmol), [Cp*Rh(MeCN)3](SbF6)2 (0.01 mmol, 8.3 mg),1-AdCOOH (0.1 mmol, 18 mg), 1-methylnaphlene (ca. 30 mg) as internal standard, and PhCl (1 mL). Then, the resulting mixture was stirred under nitrogen at 140 C for 24 h. After cooling, the reaction mixture was extracted with ethyl acetate (100 mL). The organic layer was washed by aqueous NaHCO3 (100 mL, three times) and dried over Na2SO4. After evaporation of the solvents under vacuum,product 3 was isolated by column chromatography on silica gel using hexane/ethyl acetate as eluent. Further purification by gel permeation chromatography (GPC) was performed, if needed. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate; 1-Adamantanecarboxylic acid In chlorobenzene at 140℃; for 24h; Inert atmosphere; regioselective reaction; | 4.6. Reaction of methyl phenyl sulfones 1 with alkynes 2 General procedure: To a 20 mL two-necked flask with a reflux condenser, a balloon,and a rubber cup were added methyl phenyl sulfone 1 (0.75 mmol),alkyne 2 (0.25 mmol), [Cp*Rh(MeCN)3](SbF6)2 (0.01 mmol, 8.3 mg),1-AdCOOH (0.1 mmol, 18 mg), 1-methylnaphlene (ca. 30 mg) as internal standard, and PhCl (1 mL). Then, the resulting mixture was stirred under nitrogen at 140 C for 24 h. After cooling, the reaction mixture was extracted with ethyl acetate (100 mL). The organic layer was washed by aqueous NaHCO3 (100 mL, three times) and dried over Na2SO4. After evaporation of the solvents under vacuum,product 3 was isolated by column chromatography on silica gel using hexane/ethyl acetate as eluent. Further purification by gel permeation chromatography (GPC) was performed, if needed. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | To a solution of <strong>[80945-86-4]6-bromo-2-chlorobenzo[d]thiazole</strong> (990 mg, 4.00 mmol) and (methylsulfonyl)benzene (1.56 g, 10.0 mmol) in degassed toluene (16 mL) at 0 C was slowly added 1.0 M lithium bis(trimethylsilyl)amide in toluene (10.0 mL, 10.0 mmol).After 2 h, the reaction mixture was quenched by the addition of saturated NH4C1 (50 mL) and the aqueous portion extracted with EtOAc (40 mL x2). The combined organic extracts were dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 20-40% ethyl acetate in hexane to give Compound 430a(1.1 g, 64% yield) as a white solid. HPLC RT = 1.87 mm(LCMS Method B). MS(ES): m/z = 369.9 [M+H]. ?H NMR (400MHz, DMSO-d6) oe 8.43 (d, J=2.0 Hz, 1H), 7.90 - 7.81 (m, 3H), 7.80 - 7.72 (m, 1H), 7.70 - 7.57 (m, 3H), 5.43 (s, 2H). | |
64% | With lithium hexamethyldisilazane; In toluene; at 0℃; for 2h; | To a solution of <strong>[80945-86-4]6-bromo-2-chlorobenzo[d]thiazole</strong> (990 mg, 4.00 mmol) and (methylsulfonyl)benzene (1.56 g, 10.0 mmol) in degassed toluene (16 mL) at 0 C. was slowly added 1.0 M lithium bis(trimethylsilyl)amide in toluene (10.0 mL, 10.0 mmol). After 2 h, the reaction mixture was quenched by the addition of saturated NH4Cl (50 mL) and the aqueous portion extracted with EtOAc (40 mL×2). The combined organic extracts were dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 20-40% ethyl acetate in hexane to give Compound 430a (1.1 g, 64% yield) as a white solid. HPLC RT=1.87 min (LCMS Method B). MS(ES): m/z=369.9 [M+H]+. 1H NMR (400 MHz, DMSO-d6) delta 8.43 (d, J=2.0 Hz, 1H), 7.90-7.81 (m, 3H), 7.80-7.72 (m, 1H), 7.70-7.57 (m, 3H), 5.43 (s, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With n-butyllithium; boron trifluoride diethyl etherate In tetrahydrofuran; Petroleum ether at -78 - 20℃; for 4.66667h; Inert atmosphere; regioselective reaction; | (2S)-2-[(2R,5S)-5-((1R)-1-[1-(tert-Butyl)-1,1-dimethylsilyl]oxyethyl)-5-methyltetrahydro-2-furanyl]-4-(phenylsulfonyl)butan-2-ol (24) To a well-stirred solution of methyl phenyl sulphone (2.57 g,16.5 mmol) in anhydrous THF (20 mL) at -78 C was added n-butyllithium (10.3 mL, 16.5 mmol, 1.6M solution in hexanes) dropwise and stirred for 30 min at the same temperature. BF3*Et2O (0.93 mL, 7.2 mmol) was added to the above mixture and allowed to stir for 10 min and then a solution of epoxide 23 (2.0 g, 6.6 mmol) in dry THF (15 mL) was added dropwise at -78 C. The mixture was stirred for 4 h at -78 C and then warm to room temperature. After completion, the reaction mixture was quenched with saturated NH4Cl and the product was extracted with EtOAc (350 mL). The combined organic layers were washed with brine and dried over anhydrous Na2SO4 was and then purified by column chromatography(EtOAc/hexane, 5%) to afford the pure product 24 (2.94 g, 97% yield) as a pale yellow liquid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.86 g | Phenylmethylsulfone (0.50 g) was dissolved in tetrahydrofuran (10 mL), and the solution was cooled to -78C. To the mixture was added dropwise a solution of n-butyllithium in nhexane (1.69 mol/L, 2.07 mL), and the mixture was stirred at -78C for 30 minutes. To the mixture was added dropwise <strong>[10076-48-9]methyl 2,2-dimethoxypropanoate</strong> (0.58 g), and the mixture was stirred at -78C for 3.5 hours. The mixture was heated to room temperature, water was added thereto, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous Na2504, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (0.86 g) as a colorless oil.MS (ESI-) 271 (M-1) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | Stage #1: methylphenylsulfonate With n-butyllithium In tetrahydrofuran; hexane at -5℃; for 0.5h; Inert atmosphere; Stage #2: (S)-N-(tert-butoxycarbonyl)alanine methyl ester In tetrahydrofuran; hexane at -78 - 25℃; Inert atmosphere; | 3.1. General Procedure for the Synthesis of α-Ketosulfones 3 General procedure: 1.6 M n-BuLi in hexane (2.5 mL, 4 mmol for 3a-f,h; 1.25 mL, 2 mmol for 3g,i) was slowly addedat 5 °C, under Ar, to a solution of sulfone 2 (2.0 mmol) in 1.5 mL dry THF, and the mixture wasstirred at 5 °C for 30 min (4 h for reactions with sulfone 2b). The resulting yellow suspension wastransferred via a syringe to a three-necked flask, containing a 2.5 M solution of the N-Boc amino ester 1(1 mmol) in dry THF (1M for 3h,i), at 78 °C, under an Ar atmosphere, with stirring. The mixturewas stirred overnight while the temperature was allowed to reach 25 °C, and partitioned between 5%aqueous citric acid (water for 3f) and ethyl acetate. The organic phase was extracted with saturatedNaHCO3 and brine, dried over Na2SO4 and evaporated to give a solid that was purified by flashchromatography (eluent AcOEt/petroleum ether from 0%-15%). 3.2. Spectroscopic and Analytical Data for -Ketosulfones 3(3S)-3-(tert-Butoxycarbonylamino)-1-(phenylsulfonyl)-2-butanone (3a): 89% from 1a and 2a; whitesolid, mp 115-117 °C, [α]25D-36 (c 0.8, CHCl3); IR: 3387, 1736, 1700, 1288, 1148 cm1; 1H-NMR: 1.35(d, J = 7.0 Hz, 3H), 1.44 (s, 9H), 4.24 (d, J = 14.0 Hz, 1H), 4.33 (m, 1H), 4.44 (d, J = 14.0 Hz, 1H), 5.15(br, 1H), 7.58 (m, 2H), 7.69 (m, 1H), 7.90 (m, 2H) ppm. 13C-NMR: 16.1, 28.1, 55.9, 63.2, 80.2, 128.4,129.3, 134.3, 139.0, 155.3, 198.4 ppm; ESI-MS: m/z 350 [M + Na]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | Stage #1: methylphenylsulfonate With n-butyllithium In tetrahydrofuran; hexane at -5℃; for 0.5h; Inert atmosphere; Stage #2: N-tert-butoxycarbonyl-L-valine methyl ester In tetrahydrofuran; hexane at -78 - 25℃; Inert atmosphere; | 3.1. General Procedure for the Synthesis of α-Ketosulfones 3 General procedure: 1.6 M n-BuLi in hexane (2.5 mL, 4 mmol for 3a-f,h; 1.25 mL, 2 mmol for 3g,i) was slowly addedat 5 °C, under Ar, to a solution of sulfone 2 (2.0 mmol) in 1.5 mL dry THF, and the mixture wasstirred at 5 °C for 30 min (4 h for reactions with sulfone 2b). The resulting yellow suspension wastransferred via a syringe to a three-necked flask, containing a 2.5 M solution of the N-Boc amino ester 1(1 mmol) in dry THF (1M for 3h,i), at 78 °C, under an Ar atmosphere, with stirring. The mixturewas stirred overnight while the temperature was allowed to reach 25 °C, and partitioned between 5%aqueous citric acid (water for 3f) and ethyl acetate. The organic phase was extracted with saturatedNaHCO3 and brine, dried over Na2SO4 and evaporated to give a solid that was purified by flashchromatography (eluent AcOEt/petroleum ether from 0%-15%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | Stage #1: methylphenylsulfonate With n-butyllithium In tetrahydrofuran; hexane at -5℃; for 0.5h; Inert atmosphere; Stage #2: N-tert-butoxycarbonyl-L-leucine methyl ester In tetrahydrofuran; hexane at -78 - 25℃; Inert atmosphere; | 3.1. General Procedure for the Synthesis of α-Ketosulfones 3 General procedure: 1.6 M n-BuLi in hexane (2.5 mL, 4 mmol for 3a-f,h; 1.25 mL, 2 mmol for 3g,i) was slowly addedat 5 °C, under Ar, to a solution of sulfone 2 (2.0 mmol) in 1.5 mL dry THF, and the mixture wasstirred at 5 °C for 30 min (4 h for reactions with sulfone 2b). The resulting yellow suspension wastransferred via a syringe to a three-necked flask, containing a 2.5 M solution of the N-Boc amino ester 1(1 mmol) in dry THF (1M for 3h,i), at 78 °C, under an Ar atmosphere, with stirring. The mixturewas stirred overnight while the temperature was allowed to reach 25 °C, and partitioned between 5%aqueous citric acid (water for 3f) and ethyl acetate. The organic phase was extracted with saturatedNaHCO3 and brine, dried over Na2SO4 and evaporated to give a solid that was purified by flashchromatography (eluent AcOEt/petroleum ether from 0%-15%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | Stage #1: methylphenylsulfonate With n-butyllithium In tetrahydrofuran; hexane at -5℃; for 0.5h; Inert atmosphere; Stage #2: N-(tert-butyloxycarbonyl)-L-isoleucine methyl ester In tetrahydrofuran; hexane at -78 - 25℃; Inert atmosphere; | 3.1. General Procedure for the Synthesis of α-Ketosulfones 3 General procedure: 1.6 M n-BuLi in hexane (2.5 mL, 4 mmol for 3a-f,h; 1.25 mL, 2 mmol for 3g,i) was slowly addedat 5 °C, under Ar, to a solution of sulfone 2 (2.0 mmol) in 1.5 mL dry THF, and the mixture wasstirred at 5 °C for 30 min (4 h for reactions with sulfone 2b). The resulting yellow suspension wastransferred via a syringe to a three-necked flask, containing a 2.5 M solution of the N-Boc amino ester 1(1 mmol) in dry THF (1M for 3h,i), at 78 °C, under an Ar atmosphere, with stirring. The mixturewas stirred overnight while the temperature was allowed to reach 25 °C, and partitioned between 5%aqueous citric acid (water for 3f) and ethyl acetate. The organic phase was extracted with saturatedNaHCO3 and brine, dried over Na2SO4 and evaporated to give a solid that was purified by flashchromatography (eluent AcOEt/petroleum ether from 0%-15%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | Stage #1: methylphenylsulfonate With n-butyllithium In tetrahydrofuran; hexane at -5℃; for 0.5h; Inert atmosphere; Stage #2: (S)-2-tert-butoxycarbonylamino-3-phenyl-propionic acid methyl ester In tetrahydrofuran; hexane at -78 - 25℃; Inert atmosphere; | 3.1. General Procedure for the Synthesis of α-Ketosulfones 3 General procedure: 1.6 M n-BuLi in hexane (2.5 mL, 4 mmol for 3a-f,h; 1.25 mL, 2 mmol for 3g,i) was slowly addedat 5 °C, under Ar, to a solution of sulfone 2 (2.0 mmol) in 1.5 mL dry THF, and the mixture wasstirred at 5 °C for 30 min (4 h for reactions with sulfone 2b). The resulting yellow suspension wastransferred via a syringe to a three-necked flask, containing a 2.5 M solution of the N-Boc amino ester 1(1 mmol) in dry THF (1M for 3h,i), at 78 °C, under an Ar atmosphere, with stirring. The mixturewas stirred overnight while the temperature was allowed to reach 25 °C, and partitioned between 5%aqueous citric acid (water for 3f) and ethyl acetate. The organic phase was extracted with saturatedNaHCO3 and brine, dried over Na2SO4 and evaporated to give a solid that was purified by flashchromatography (eluent AcOEt/petroleum ether from 0%-15%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | Stage #1: methylphenylsulfonate With n-butyllithium In tetrahydrofuran; hexane at -5℃; for 0.5h; Inert atmosphere; Stage #2: (S)-N-(tert-butoxycarbonyl)proline methyl ester In tetrahydrofuran; hexane at -78 - 25℃; Inert atmosphere; | 3.1. General Procedure for the Synthesis of α-Ketosulfones 3 General procedure: 1.6 M n-BuLi in hexane (2.5 mL, 4 mmol for 3a-f,h; 1.25 mL, 2 mmol for 3g,i) was slowly addedat 5 °C, under Ar, to a solution of sulfone 2 (2.0 mmol) in 1.5 mL dry THF, and the mixture wasstirred at 5 °C for 30 min (4 h for reactions with sulfone 2b). The resulting yellow suspension wastransferred via a syringe to a three-necked flask, containing a 2.5 M solution of the N-Boc amino ester 1(1 mmol) in dry THF (1M for 3h,i), at 78 °C, under an Ar atmosphere, with stirring. The mixturewas stirred overnight while the temperature was allowed to reach 25 °C, and partitioned between 5%aqueous citric acid (water for 3f) and ethyl acetate. The organic phase was extracted with saturatedNaHCO3 and brine, dried over Na2SO4 and evaporated to give a solid that was purified by flashchromatography (eluent AcOEt/petroleum ether from 0%-15%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | Stage #1: methylphenylsulfonate With n-butyllithium; 1,1,1,3,3,3-hexamethyl-disilazane In tetrahydrofuran; hexane at -78℃; for 1.5h; Stage #2: 2,2,2-trifluoroethyl trifluoroacetate In tetrahydrofuran; hexane at -78 - 20℃; Further stages; | 1,1,1,3,3-Pentafluoro-3-(phenylsulfonyl)propane-2,2-diol 43. To a -78 °C solution of n-BuLi(452 μL, 1.7 M in hexanes) in THF (3 mL) was added hexamethyldisilazane (161 μL, 0.768mmol). After stirring the reaction for 20 min at -78 °C, a solution of methyl phenyl sulfone 39(100 mg, 0.64 mmol) in THF (2 mL) was added dropwise. The mixture was stirred for 90 min at-78 °C, and then 2,2,2-trifluoroethyl 2,2,2-trifluoroacetate (129 μL, 0.960 mmol) was addeddropwise. After an additional 60 min of stirring at the same temperature, the reaction waswarmed to rt, quenched with 1 M aqueous H2SO4 (3 mL) and then stirred for 60 min. Theresultant mixture was extracted with CH2Cl2 (5 mL × 3). The organics were dried over Na2SO4and concentrated under reduced pressure. The residue was dissolved in CH3CN (10 mL) andtreated with Selectfluor (1.13 g, 3.20 mmol). The reaction mixture was heated to 80 °C withstirring for 24 h. Next, the reaction was diluted with EtOAc (50 mL), filtered through Celite, andconcentrated under reduced pressure to afford the title compound 43 in 87% yield (170 mg) as acolorless solid: mp 84-86 °C; 1H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 7.8 Hz, 2H), 7.81 (t, J= 7.5 Hz, 1H), 7.65 (t, J = 7.9 Hz, 2H), 5.17 (br s, 2H); 13C NMR (100 MHz, CDCl3) δ 136.3,132.3, 130.9 (2C), 129.5 (2C), 121.8 (q, J = 289 Hz. 1C), 116.1 (t, J = 302 Hz, 1C), 93.2 (qt, J =33.0, 8.0 Hz, 1C); 19F NMR (564 MHz, CDCl3) δ -82.5 (t, J = 10.8 Hz, 3F), -111.2 (q, J = 10.8Hz, 2F); IR (film) νmax 3442, 2925, 2853, 1336, 1177, 1151, 1072 cm-1; HRMS (ESI) m/z calcdfor C9H7ClF5O4S (M+Cl)- 340.9674, found 340.9645. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6%Chromat.; 22%Chromat.; 65%Chromat.; 7%Chromat. | With sodium hypochlorite pentahydrate; In water; acetonitrile; at 23 - 28℃; for 3h; | General procedure: 0.25 g (2 mmol) of thioanisole as a substrate, 10 mL of acetonitrile and 2 mL of water were placed in a 50 mL three-necked flask.The internal temperature of the flask was 23 C.0.79 g (4.8 mmol) of sodium hypochlorite pentahydrate crystals was added thereto at a time and stirred.The internal temperature of the flask rose to 28 C. and gradually decreased.GC analysis was carried out 3 hours after the start of the reaction, and 22% of methyl phenyl sulfoxide,65% of methyl phenyl sulfone was formed.As a by-product,6% of chloromethyl phenyl sulfoxide,7% of chloromethyl phenyl sulfone,A total of 0.8% of higher order chlorides were observed.0.79 g (4.8 mmol) of sodium hypochlorite pentahydrate crystals was added and stirring was continued for 1 hour.Thioanisole,Methyl phenyl sulfoxide was completely disappeared and 87% of methyl phenyl sulfone was formed.As impurities,11% chloromethyl phenyl sulfone,0.5% dichloromethyl phenyl sulfone,Production of trichloromethyl phenyl sulfone 1.3% was observed. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87%Chromat.; 11%Chromat. | With sodium hypochlorite pentahydrate; In water; acetonitrile; at 23 - 28℃; for 4h; | General procedure: 0.25 g (2 mmol) of thioanisole as a substrate, 10 mL of acetonitrile and 2 mL of water were placed in a 50 mL three-necked flask.The internal temperature of the flask was 23 C.0.79 g (4.8 mmol) of sodium hypochlorite pentahydrate crystals was added thereto at a time and stirred.The internal temperature of the flask rose to 28 C. and gradually decreased.GC analysis was carried out 3 hours after the start of the reaction, and 22% of methyl phenyl sulfoxide,65% of methyl phenyl sulfone was formed.As a by-product,6% of chloromethyl phenyl sulfoxide,7% of chloromethyl phenyl sulfone,A total of 0.8% of higher order chlorides were observed.0.79 g (4.8 mmol) of sodium hypochlorite pentahydrate crystals was added and stirring was continued for 1 hour.Thioanisole,Methyl phenyl sulfoxide was completely disappeared and 87% of methyl phenyl sulfone was formed.As impurities,11% chloromethyl phenyl sulfone,0.5% dichloromethyl phenyl sulfone,Production of trichloromethyl phenyl sulfone 1.3% was observed. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | In water at 100℃; for 12h; Sealed tube; | 1 Example 1 In the reflux reactor, followed by adding 0.5mml sodium benzene sulfinate,1 mmol di-tert-butyl peroxide, 2.5 mL water; Magnetic stirring, heat sealed at 100 for 12 hours;After stopping heating, cooling to room temperature,The reaction mixture was then extracted three times with ethyl acetate; the ethyl acetate was removed under reduced pressure distillation,The target product phenyl methyl sulfone was obtained.The structure of the resulting product was confirmed by GC-MS, 1H NMR, 13C NMR. The yield of phenylmethyl sulfone was 93%. |
93% | With water at 110℃; for 12h; Sealed tube; Green chemistry; | A typical procedure for the synthesis of aryl methyl sulfones Sodium benzenesulfinate (0.5 mmol), 2-(tert-butylperoxy)-2-methylpropane (1 mmol), and H2O (2.5 mL) were added into a 10 mL sealed tube successively. Then, the reaction was carried out at 110 C under magnetic stirring for 12 h. After the reaction was finished, the reaction mixture was extracted with ethyl acetate for three times (5 mL × 3). The obtained organic layer was dried with anhydrous MgSO4. The solvent was removed under vacuum, and the obtained crude product was purified by silica gel column chromatography with petroleum ether/ethyl acetate (10:1) as eluent to afford the desired pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | Stage #1: methylphenylsulfonate With n-butyllithium In tetrahydrofuran at -78℃; Stage #2: benzyl 3-bromo-2,2,3,3-tetrafluoropropanate In tetrahydrofuran at -78 - 20℃; | 4.9. Synthesis of 4-bromo-3,3,4,4-tetrafluoro-2-oxobut-1-yl phenyl sulfone monohydrate (7) A solution of methyl phenyl sulfone (1.2 g, 7.9 mmol) in THF (8.0 mL) was cooled at -78 °C. n-BuLi (1.6M in Et2O, 4.9 mL, 7.8 mmol) was added dropwise to the mixture and stirred at -78 °C for 10 min. A solution of benzyl 3-bromo-2,2,3,3-tetrafluoropropanate (6: 1.6 g, 5.0 mmol) in THF (2.0 mL) was added to the reaction mixture. Then the whole was allowed to warm to room temperature. After stirred for 30 min, the reaction was quenched with H2O and the resulting mixture was extracted with Et2O three times and the extracts were dried over anhydrous Na2SO4, evaporated and purified by precipitation (CH2Cl2/Hexane=1/1) to afford 4-bromo-3,3,4,4-tetrafluoro-2-oxobut-1-yl phenyl sulfone monohydrate (7: 1.5 g, 4.0 mmol, 81% yield). Isolated yield 81%; White solid; M.p. > 250 °C; 1H NMR (Acetone-d6): δ 2.85-2.88 (m, 4H, CH2+2OH), 7.49-7.58 (m, 3H, Ar-H), 7.89-7.91 (m, 2H, Ar-H); 13C NMR (Acetone-d6): δ 89.5 (CH2), 111.4 (tt, J=263.5, 30.2 Hz, CF2), 118.5 (tt, J=312.4, 40.5 Hz, CF2), 126.2 (Ar), 129.5 (Ar), 132.7 (Ar), 146.9 (Ar), 167.0 (t, J=23.2 Hz, C(OH)2); 19F NMR (Acetone-d6): δ -63.32 to -63.34 (m, 2F, CF2Br), -115.58 to -115.62 (m, 2F, CF2CF2Br); IR (KBr): ν 3115, 3069, 2960, 2853, 1624, 1579, 1448, 1268, 1165, 1140, 1081, 902, 855 cm-1; HRMS (FAB) Calcd for [M-H2O+Na]+ C10H779BrF4NaO3S: 384.9133, Found 384.9124. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | Stage #1: methylphenylsulfonate With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Inert atmosphere; Stage #2: 2-ethyl-2-[(triethylsilyl)oxy]cyclobutan-1-one In tetrahydrofuran; hexane at -78 - -50℃; for 0.5h; | 2-Ethyl-1-[(phenylsulfonyl)methyl]-2-[(triethylsilyl)oxy]-cyclobutan-1-ol 53 General procedure: In a flask connected to an argon/vacuum line, a solution of sulfone 33 (156 mg, 1mmol) in THF(4ml) was thoroughly degassed (three freeze/pump/thawcycles). The flask was immersed in a dry-ice/acetone bathand, with stirring, 1.6M (in hexane) n-BuLi (625 L) wasadded with a syringe. After 30min stirring, a degassed solutionof ketone 18c (92.5 mg, 0.43mmol) in THF (2 mL) was addedwith a cannula. The temperature was then allowed to risegradually to -50 °C. After 30min stirring, the cooling bathwas removed and the reaction mixture was diluted with ether(3 mL) and water (4 mL). The aqueous layer was extracted withether (3 x 5 mL) and the pooled organic phases were washedwith water (6 mL), brine (2 x 6 mL), and dried (MgSO4). Thesolvents were evaporated in a vacuum and the solid residue waschromatographed on silica gel (hexane/EtOAc) to give, afterthorough elimination of the solvents in a good vacuum, a 28:72(GC) mixture of, respectively, cis-34b and trans-34b (133 mg,83%) as a white solid; General protocol for cyclobutanone/sulfone condensation experiments. In THF (90 mL). Fromketone 52b (2.92 g, 12.8mmol) and sulfone 33 (2.0 g, 12.8mmol). Isolated: hydroxysulfone 53 (65:35 mixture of the transandthe cis-isomer, by GC and NMR) as a pale-yellow oil (4.49 g, 91%); TLC (hexane:ether = 4:1) Rf = 0.14; 1H NMR (CDCl3): δ 0.61.1(m, 18H), 1.482.30(m, 6H), 3.40 (brs,0.7H), 3.41 (dd, J = 14.7, 1.3 Hz, 0.65H), 3.61 (d, J = 14.7 Hz,0.65H), 7.59 (m, 3H), 7.94 (m, 2H); 13C NMR (CDCl3): δ 6.7 (SiCH2), 7.11 (SiCH2CH3), 8.38/8.46 (CH3), 28.0/28.8(CH2CH3), 29.2/29.5 (C3H2), 29.8/31.8 (C4H2), 60.7/62.0(SO2CH2), 77.0/78.5 (C2), 81.0/82.6 (C1), 127.6/128.3/128.9/129.3/133.4/133.8/141.2/141.4 (Carom); Anal. Found:C, 59.71; H, 8.73%. Calcd for C19H32O4SSi: C, 59.34; H,8.39%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With n-butyllithium In tetrahydrofuran; hexane at -70 - 25℃; for 1h; Inert atmosphere; | 94.10 Step 10 : To a solution of PhSO2Me (449 mg, 2.88 mmol) in THF (10 mL) was added n-BuLi(1.04 mL, 2.62 mmol, 2.5 M in hexane) at -70°C under N2. The mixture was warmed to 0°C. Asuspension of A1094 (600 mg, 1.31 mmol) in THF (10 mL) was added drop-wise at 0°C. After addition, the reaction was allowed to 25°C. The reaction mixture was stirred at 25°C for 1 hour. The reaction was quenched with saturated aqueous NH4C1 (30 mL). To the suspension was added water (100 mL) and extracted with EtOAc (3 x 50 mL). The combined organic phase wasconcentrated to give a residue which was purified by silica gel chromatography (PE/EtOAc =6/1) to give compound A1194 (1.5 g, impure, containing PhSO2Me) as an oil. The oil was further purified by silica gel chromatography (DCM/Acetone=50/1) to give A1194 (400 mg, 63%) as an oil.‘H NMR (400 MHz, CDC13) ö7.90 (d, J = 7.6 Hz, 2H), 7.69-7.62 (m, 1H), 7.60-7.51 (m, 2H),5.40-5.35 (m, 1H), 3.17-3.07 (m, 1H), 3.04-2.93 (m, 1H), 2.22 (dd, J= 2.4, 12.8 Hz, 1H), 2.10-1.64 (m, 9H), 1.57-1.35 (m, 7H), 1.31-1.11 (m, 5H), 1.10-0.92 (m, 3H), 0.90-0.82 (m, 7H), 0.81-0.71 (m, 1H), 0.64 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | Stage #1: methylphenylsulfonate With n-butyllithium In tetrahydrofuran; hexane at -70℃; for 0.5h; Inert atmosphere; Stage #2: tert-Butyl-[(3S,8S,9S,10R,13S,14S,17R)-17-((S)-2-iodo-1-methyl-ethyl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yloxy]-dimethyl-silane In tetrahydrofuran; hexane at -70 - 25℃; for 3h; Inert atmosphere; | 112.6 Step 6 . To a solution of (methylsulfonyl) benzene (24.5 g, 157 mmol) in THF (200 mL) was added n-BuLi (57.2 mL, 143 mmol) at -70°C under N2. The mixture was stirred at-70°C for 30 minutes. A solution of B-5C (40 g, 71.8 mmol) in THF (200 mL) was added dropwise at 25°C. After addition, the reaction was allowed to stir at 25°C for 3h. The reactionwas quenched with sat.NH4C1 (50 mL) and extracted with EtOAc (2 x 20 mL). The combinedorganic phase was dried over Na2SO4, filtered, concentrated to give B-6C (40 g, 95%).‘H NMR (400 MHz, CDC13) ö 7.90-7.86 (m, 2H), 7.68-7.61 (m, 1H), 7.60-7.52 (m, 2H), 5.33-5.29 (m, 1H), 3.50-3.42 (m, 1H), 3.17-3.06 (m, 1H), 3.04-2.96 (m, 1H), 2.31-2.11 (m, 3H), 1.99-1.90 (m, 2H), 1.87-1.67 (m, 5H), 1.51-1.40 (m, 7H); 1.24-0.82 (m, 27H); 0.68-0.58 (m, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | Stage #1: methylphenylsulfonate With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.25h; Inert atmosphere; Stage #2: 5,5-dimethyl-3-oxocyclohex-1-en-1-yl 4-methylbenzenesulfonate In tetrahydrofuran for 1h; | 21 Example 21 Methyl phenyl sulfone (2 equiv, 212 mg, 1.36 mmol) dissolved in 1 mL of dry THF was added to a solution of LDA (2 equiv, 0.68 ml, 1.36 mmol) dissolved in 15 ml of dry THF kept at -78° C. under nitrogen. The mixture was left to stir for 15 minutes. Compound 8 (1 equiv, 200 mg, 0.68 mmol) was dissolved in dry THF and added drop-wise and the solution was kept at the low temperature for 1 h. The reaction mixture was allowed to warm to room temperature, diluted with 20 mL of saturated NH4CL solution and extracted with 2×20 mL of EtOAc. The organic extracts were combined and washed with water (2×5 ml), dried with anhydrous MgSO4 and concentrated under reduced pressure. The crude mass was purified by flash column chromatography eluting with EtOAc/hexane (40%) 0.1 g, 53% of the compound of example 21 as a to yellow oil. (0127) 1H NMR (400 MHz, CDCl3) δ ppm: 7.82 (d, J=7.2 Hz, 2H), 7.63 (m, 1H), 7.52 (t, J=7.7 Hz, 2H), 5.55 (s, 1H), 3.89 (s, 2H), 2.38 (d, J=1.0 Hz, 2H), 2.14 (s, 2H), 0.98 (s, 6H) 13C NMR (100 MHz, CDCl3) δ ppm: 198.68, 148.35, 138.01, 134.33, 131.52, 129.37, 128.23, 63.88, 50.71, 43.85, 33.63, 28.08 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With ruthenium(bis[2‐(ethylsulfanyl)ethyl]amine)(dichloro)(triphenylphosphine); potassium hexamethylsilazane In toluene at 100℃; for 12h; Inert atmosphere; Glovebox; | |
35% | With ruthenium(bis[2‐(ethylsulfanyl)ethyl]amine)(dichloro)(triphenylphosphine); potassium hexamethylsilazane In toluene at 120℃; Schlenk technique; Glovebox; Inert atmosphere; Sealed tube; | General procedure for closed system: To an oven dried 100 mL Schlenk flask in a N2glovebox, benzyl phenyl sulfone (464 mg, 2 mmol), KHMDS (410 mg, 2.05 mmol) and Ru-SNS (6.3mg, .01 mmol) were dissolved in 10 mL of Toluene. The alcohol or ester (1 mmol) was added to the reaction mixture, the vessel was sealed and stirred at 120oC for 12 hours. The reaction time was different for some cyclopropane entry as indicated.The reaction was allowed to cool to room temperature, then quenched with 5 mL of saturated NH4Cl solution. The mixture was extracted with 20 mL of Ethyl Acetate x3 and the organic layers were collected and dried over MgSO4. The solvent was concentrated under vacuum and purified by flash silica chromatography with a gradient of 100:0→88:12 (Hexane: Ethyl Acetate). Fractions where an overly large amount of minor diastereomer, byproduct, or starting material was present along with the desired product were discarded. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With caesium carbonate In ethanol at 90℃; for 16h; Sealed tube; | 28; 29 (Example 1) General procedure: S-phenyl benzenesulfonothiolate (62.6 mg, 0.25 mmol) and cesium carbonate (Cs2CO3) as a thiosulfonate compound were dissolved in benzyl bromide (60 l, 0.50 mmol) and The mixture was added to the tube containing the seal (seal tube). To proceed the reaction, 0.5 ml (0.5 M) of ethanol (EtOH) was added and the vessel was closed and stirred at 90 ° C for 16 hours. The product was cooled and then diluted with dichloromethane (DCM) and filtered. The filtrate was concentrated by rotary evaporation and then the residue was purified by column chromatography (silica gel, 3% ethyl acetate in hexane) to produce the desired sulfones (sulfones). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | Stage #1: (2R/3R)/(2S,3S)-2,3-epoxy-butanol With titanium(IV) isopropylate In tetrahydrofuran at 0℃; Inert atmosphere; Stage #2: methylphenylsulfonate With N,N,N,N,N,N-hexamethylphosphoric triamide; n-butyllithium In tetrahydrofuran; hexane at -78 - -50℃; for 1h; Inert atmosphere; regioselective reaction; | (2R,3R)/(2S,3S)-4-Phenylsulfonyl-3-methyl-butane-1,2-diol rac-31a In a flask connected to an argon/vacuum line,with cooling (ice bath), Ti(O-i-Prop)4 (0.677 L, 2.32mmol)was added with a syringe to a degassed solution of epoxide rac-13c (100 mg, 1.16mmol) in THF (2.3 mL) and the resultingmixture was stirred at ca. 0 °C. In a second flask, 1.2M (inhexane) BuLi (2.1 mL, 4.64mmol) was added dropwise to acooled (78 °C) solution of methyl phenyl sulfone 30 (380 mg,2.43mmol) in THF (5 mL). After 1 h stirring, HMPA (433 L,2.55mmol) was added followed, 1 h later, by the titanium(IV)alkoxide mixture. The bath was allowed to warm and 1 h later,when the temperature was ca. 50 °C, the reaction mixturewas poured into a stirred mixture of EtOAc (30 mL) and pH 2tartaric buffer (10 mL). The aqueous layer was saturated withNaCl, filtered on Celite (washings with EtOAc), and extractedwith EtOAc (3 5 mL). The pooled organic extracts werewashed with brine, until neutral, and dried (MgSO4). Eliminationof the solvents in a vacuum was followed by columnchromatography of the residue (hexane/EtOAc) to give diolsulfonerac-31a (232 mg, 83%) as a colourless oil; TLC(EtOAc, 2 elutions) Rf = 0.47; 1HNMR (CDCl3): 1.04 (d,J = 6.9 Hz, 3H), 2.21 (brs, 2H, OH), 2.312.41(m, 1H), 2.97(dd, J = 14.1, 6.9 Hz, 1H), 3.42 (dd, J = 14.1, 3.9 Hz, 1H),3.55 (d, J = 11.1, 7.6 Hz, 1H), 3.63 (dd, J = 11.6, 3.6 Hz,1H), 3.873.92(m, 1H), 7.547.69(m, 3H), 7.907.94(m,2H); 13CNMR (CDCl3): 14.7 (CH3), 31.4 (CHCH3), 59.2(CH2SO2), 64.0 (CH2OH), 73.4 (CHOH), 127.8, 129.4, 133.7,139.9; MS (CI-NH3): m/z 262 (M + NH4+), 245 (M + H+),227 (M OH),143, 132, 125, 117, 89; Anal. Found: C, 54.21;H, 6.85%. Calc. for C11H16O4S: C, 54.08; H, 6.60% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72.29% | With potassium hexamethylsilazane In tetrahydrofuran at -70 - -40℃; for 3.5h; | 5 To a solution of compound 4 (140 g, 410.02 mmol) in THF (1400 mL) was added methylsulfonylbenzene (96.07 g, 615.03 mmol), then added KHMDS (1 M, 615.03 mL) in 0.5 hr. The mixture was stirred at -70 ~ -40 °C for 3 hr. TLC indicated compound 4 was consumed and one new spot formed. The reaction mixture was quenched by addition sat. NH4Cl aq. 3000 mL at 0 °C, and then diluted with EtOAc (3000 mL) and extracted with EtOAc (2000 mL x 3). Dried over Na2S04. fdtered, and concentrated under reduced pressure to give a residue. To the crude was added THF (1000 mL) and MeOH (1500 mL), concentrated under reduced pressure at 45 °C until about 1000 mL residue remained, fdtered the solid. Repeat 3 times. Compound 5 (590 g, 72.29% yield) was obtained as a yellow solid. NMR (400 MHz, CHLOROF ORM-ri) d = 7.81 (d, J = 7.5 Hz, 2H), 7.75 - 7.65 (m, 1H), 7.62 - 7.53 (m, 2H), 7.48 (br d, J = 7.2Hz, 6H), 7.25 - 7.11 (m, 9H), 4.50 - 4.37 (m, 1H), 3.31 - 3.11 (m, 3H), 3.04 - 2.87 (m, 2H), 1.60 - 1.48 (m, 1H), 1.39 - 1.24 (m, lH), 1.11 (dtd, J = 4.5, 8.8, 12.8 Hz, 1H), 0.32 - 0.12 (m, 1H). |
72.29% | With potassium hexamethylsilazane In tetrahydrofuran for 3.5h; stereoselective reaction; | 10 To a solution of compound 4 (140 g, 410.02 mmol) in THF (1400 mL) was added methylsulfonylbenzene (96.07 g, 615.03 mmol), then added KHMDS (1 M, 615.03 mL) in 0.5 hr. The mixture was stirred at -70 ~ -40 °C for 3 hr. TLC indicated compound 4 was consumed and one new spot formed. The reaction mixture was quenched by addition sat. NH4CI aq. 3000 mL at 0 °C, and then diluted with EtOAc (3000 mL) and extracted with EtOAc (2000 mL x 3). Dried over NaaSCL, fdtered, and concentrated under reduced pressure to give a residue. To the crude was added THF (1000 mL) and MeOH (1500 mL), concentrated under reduced pressure at 45 °C until about 1000 mL residue remained, fdtered the solid. Repeat 3 times. Compound 5 (590 g, 72.29% yield) was obtained as a yellow solid. 'H NMR (400 MHz, CHLOROFORM-d) d = 7.81 (d, J = 7.5 Hz, 2H), 7.75 - 7.65 (m, 1H), 7.62 - 7.53 (m, 2H), 7.48 (br d, J = 7.2Hz, 6H), 7.25 - 7.11 (m, 9H), 4.50 - 4.37 (m, 1H), 3.31 - 3.11 (m, 3H), 3.04 - 2.87 (m, 2H), 1.60 - 1.48 (m, 1H), 1.39 - 1.24 (m, lH), 1.11 (dtd, J = 4.5, 8.8, 12.8 Hz, 1H), 0.32 - 0.12 (m, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | Stage #1: PVS With tetraethylammoniumcyanide In dichloromethane for 0.0833333h; Stage #2: methyl iodide In dichloromethane at 20℃; | General Procedure for the Synthesis of Sulfones 2a-m General procedure: Vinyl sulfone (0.4 mmol) and tetraethylammonium cyanide(1.05 equiv, 0.42 mmol) were dissolved in DCM (1 mL). Thereaction mixture was stirred for 5 min, and a solution of an appropriate electrophile (1.05 equiv, 0.42 mmol) in DCM (0.5mL) was added dropwise. The resultant reaction mixture wasstirred at room temperature. After completion of the reaction(checked by crude 1H NMR or GC-MS), water (10 mL) was addedto the reaction mixture, and the product was extracted withethyl acetate (3 × 10 mL). The combined organic layers werewashed with brine (10 mL), dried over anhydrous Na2SO4, andconcentrated under vacuum. The crude product thus obtainedwas purified by column chromatography using 10-20% ethylacetate in petroleum ether. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With sodium iodide In 1,2-dimethoxyethane; water at 65℃; for 8h; | (Methylsulfonyl)benzene General procedure: To a 10 mL round-bottom flask were added sulfonylhydrazine 1 (1.0 mmol), dimethyl phosphite 2 (0.6 mmol) and NaI (0.2 mmol) in mixed solvent DMF/H2O (10:1, v/v; 3 mL), and the solution was stirred for 5-10 h at 65 °C until sulfonylhydrazine 1 was completely consumed as indicated by TLC analysis. The crude products were then concentrated under reduced pressure, and purified by flash column chromatography (petroleum ether/EtOAc = 30:1 to 10:1), to obtain pure products 3, 6 and 7 with 54-95% yield. |
With tetra-(n-butyl)ammonium iodide In N,N-dimethyl-formamide at 60℃; for 2h; | 1 Example 1 A method for synthesizing organic sulfone molecules with a novel sulfone methylation reagent. Using sulfonyl hydrazide 1a (R = Ph) (0.001 mol, 0.172 g) and dimethyl phosphite 2 (0.0011 mol, 0.121 g) as starting materials, dissolve it in 5 mL N,N-dimethylformamide (DMF), Tetrabutylammonium iodide (Bu4NI) (0.0002 mol, 0.074g) was added and the mixed solution was moved to 60 °C for 2 hours and the reaction of raw material 1a was completed. Then, the solvent is drained, and the crude product is separated by column chromatography with eluent gradient elution to obtain the organic sulfone molecule 3a. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68.61% | Stage #1: methylphenylsulfonate With lithium hexamethyldisilazane In tetrahydrofuran at -70 - 0℃; for 0.5h; Stage #2: (R)-1-tritylpyrrolidine-2-carbaldehyde In tetrahydrofuran at -70℃; for 2.5h; | 10 To a solution of methylsulfonylbenzene (13.72 g, 87.86 mmol) in THF (100 mL) was added LiHMDS (1 M, 87.86 mL) in 0.5 hr at -70 °C - 0 °C, then added compound 4 in THF (100 mL). The mixture was stirred at -70 °C in 2.5 hr. TLC indicated compound 4 was remained a little and two new spots formed. The reaction mixture was quenched by addition sat. NH4CI aq. (300 mL) at 0 °C, extracted with DCM (200 mL x 3). Dried over NaaSCL, filtered and concentrated under reduced pressure to give a residue. The crude was added THF (100 mL) and MeOH (150 mL), concentrated under reduced pressure at 45 °C until about 100 mL residue remained, filtered the solid. Repeated 3 times. Got solid 20 g, the mother liquid was concentrated under reduced pressure to get compound 22 (20 g, crude) was obtained as a yellow oil. Compound (lR)-2-(benzenesulfonyl)-l-[(2R)-l-tritylpyrrolidin-2-yl]ethanol (20 g, 68.61% yield) was obtained as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With tetrabutyl ammonium fluoride In dimethyl sulfoxide at 80℃; for 24h; | |
96% | With tetrabutyl ammonium fluoride In tetrahydrofuran; dimethyl sulfoxide at 80℃; for 24h; Inert atmosphere; | 8-1 General manufacturing method 8 General procedure: TBSOM-sulfone (114.6 mg, 0.4 mmol, 1.0 equiv), alkyl halide (0.6 mmol, 1.5 equiv) and tetrabutylammonium fluoride (TBAF) (0.6 mL, 0.6 mmol, 1.5 equiv) in 0.4 mL of anhydrous DMSO 1.0 M in THF) was mixed in an Ar atmosphere. The mixture was stirred at 80° C. for 24 h. After cooling the stirring solution at room temperature, 5 mL of water was added. The organic fraction was extracted with ethyl acetate (15 mL x 3), washed with water and brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified via flash column chromatography (Hex:EA = 20:1 to 5:1) to give the desired alkyl sulfone product, respectively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With bis-triphenylphosphine-palladium(II) chloride; 1,1,3,3-Tetramethyldisiloxane; tetrabutylammomium bromide In 1,4-dioxane at 120℃; for 18h; Inert atmosphere; | 2 Specific Example 2: 102.0 mg (0.5 mmol) iodobenzene, 550.3 mg (5 mmol) dimethyl sulfite, 35.1 mg (0.05 mmol) bistriphenylphosphonium palladium (II), 100.7 mg (0.75 mmol) 1,1,3,3-tetramethyldisiloxane, 161.3 mg (0.5 mmol) tetrabutylammonium bromide was added to the reaction tube,heated at120oC for 18 hours, cooled after the reaction, filtered, and the filtrate Rotary evaporation to remove the solvent, the residue was chromatographed on a silica gel column, washed with petroleum ether, and detected by TLC. The effluent containing the product was combined, and the solvent was distilled off by a rotary evaporator. After vacuum drying, 63.4 mg of phenylmethyl sulfone was obtained as a white solid. The yield was 81. %. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | Stage #1: 4-bromoohenyl methyl sulfone With nickel(II) iodide; 1,4-bis(dicyclohexylphosphino)butane; sodium carbonate; cesium iodide In tetrahydrofuran for 0.25h; Schlenk technique; Glovebox; Stage #2: In tetrahydrofuran at 35℃; for 72h; Irradiation; | General Procedure A (solid aryl bromides). General procedure: An oven dried Schlenk tube containing a stir barwas charged with arylbromide (0.2 mmol), Na2CO3 (0.3 mmol, 31.8 mg, 1.5 equiv), and NiI2(0.02 mmol, 6.1 mg, 10 mol%). The Schlenk was transferred to a nitrogen filled gloveboxwhere dcyb (0.022 mmol, 9.9 mg, 11 mol%), CsI (0.04 mmol, 10.4 mg, 20 mol%), andanhydrous THF (0.2 M, 1 mL) was added. The Schlenk was sealed and the mixture was stirredfor 15 minutes. It was taken out of the glovebox and placed in a preheated reaction vessel at 35C (see pictures) and stirred for 72 hours under blue light irradiation. The mixture was quenchedwith 1M HCl (2 mL) and extracted with EtOAc, 0.5 cm3 of silica gel was added to the roundbottom flask and evaporated on a rotary evaporator set at 40 C and 100 mbar. The silica wasthen subjected to column chromatography |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With potassium <i>tert</i>-butylate In dimethyl sulfoxide at 80℃; for 36h; Inert atmosphere; Sealed tube; chemoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With potassium hexamethylsilazane In tetrahydrofuran; N,N-dimethyl-formamide at -40℃; for 0.5h; Schlenk technique; Inert atmosphere; |
Tags: 3112-85-4 synthesis path| 3112-85-4 SDS| 3112-85-4 COA| 3112-85-4 purity| 3112-85-4 application| 3112-85-4 NMR| 3112-85-4 COA| 3112-85-4 structure
[ 3185-99-7 ]
1-Methyl-4-(methylsulfonyl)benzene
Similarity: 0.89
[ 1424-51-7 ]
3-(Phenylsulfonyl)acrylonitrile
Similarity: 0.87
[ 3185-99-7 ]
1-Methyl-4-(methylsulfonyl)benzene
Similarity: 0.89
[ 1424-51-7 ]
3-(Phenylsulfonyl)acrylonitrile
Similarity: 0.87
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P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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