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CAS No. : | 1193-82-4 | MDL No. : | MFCD00002088 |
Formula : | C7H8OS | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | JXTGICXCHWMCPM-UHFFFAOYSA-N |
M.W : | 140.20 | Pubchem ID : | 14516 |
Synonyms : |
|
Num. heavy atoms : | 9 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.14 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 1.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 38.85 |
TPSA : | 36.28 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.76 cm/s |
Log Po/w (iLOGP) : | 1.66 |
Log Po/w (XLOGP3) : | 0.55 |
Log Po/w (WLOGP) : | 2.29 |
Log Po/w (MLOGP) : | 1.71 |
Log Po/w (SILICOS-IT) : | 1.08 |
Consensus Log Po/w : | 1.46 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.48 |
Solubility : | 4.61 mg/ml ; 0.0329 mol/l |
Class : | Very soluble |
Log S (Ali) : | -0.88 |
Solubility : | 18.3 mg/ml ; 0.131 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -2.77 |
Solubility : | 0.235 mg/ml ; 0.00168 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 2.02 |
Signal Word: | Danger | Class: | 8 |
Precautionary Statements: | P261-P264-P271-P280-P280-P302+P352-P304+P340+P312-P305+P351+P338+P310-P332+P313-P362+P364-P403+P233-P405-P501 | UN#: | 1760 |
Hazard Statements: | H315-H318-H335 | Packing Group: | Ⅲ |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65 %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 |
---|---|---|
79% | With diisopropylamine In tetrahydrofuran; N,N',N''-triethylenephosphoramide; hexane; ethyl acetate; <i>tert</i>-butyl alcohol | Step 1) 1-t-Butoxycarbonyl-3-hydroxy-4-methylenepiperidine n-Butyl lithium (9.57 mL, 2.45M in hexane, 23.7 mmol) was added to a -78° C. solution of diisopropylamine (3.32 mL, 23.7 mmol) in TEF (15 mL). After 30 min at -78° C., methyl phenyl sulfoxide (3.32 g, 23.7 mmol) in THF (4 mL) was added. The solution was warmed to 0° C. and cooled back down to -78° C. 1-t-butoxycarbonyl-4-piperidinone (4.69 g, 23.7 mmol) in TXF (20 mL) was added. The reaction was warmed to room temp, quenched by addition of solid NH4 Cl, concentrated in vacuo, and partitioned between H2 O (100 mL) and EtOAc (100 mL). The organic layer was washed with H2 O (50 mL) brine (50 mL), dried (MgSO4), and concentrated in vacuo. The resultant oil was heated at 80° C. in t-butanol (50 mL) with potassium t-butoxide (3.4g, 30 mmol) for 2 h. Solid NH4 Cl was added, and the reaction was concentrated in vacuo and partitioned between H2 O (100 mL) and EtOAc (100 mL). The EtOAc was washed with brine (50 mL), dried (MgSO4), concentrated in vacuo and purified by column chromatography (silica gel 60, 0-50percent EtOAc/hexane) to yield 4.47 g (79percent) of the title compound as a crystalline solid. 1 H NMR (400 MHz, DMSO-d6) δ 5.21 (d,1H), 4.96 (s, 1H), 4.77 (s, 1H), 3.82 (t, 2H), 3.67 (dt, 1H), 2.83 (dt, 1H), 2.77-2.50 (brd d, 1H), 2.26 (dt, 1H), 2.01 (ddd, 1H), 1.38 (s, 9H) ppm. |
79% | With diisopropylamine In tetrahydrofuran; hexane; ethyl acetate; <i>tert</i>-butyl alcohol | Step 1) 1-t-Butoxycarbonyl-3-hydroxy-4-methylenepiperidine n-Butyl lithium (9.57 mL, 2.45M in hexane, 23.7 mmol) was added to a -78° C. solution of diisopropylamine (3.32 mL, 23.7 mmol) in THF (15 mL). After 30 min at -78° C., methyl phenyl sulfoxide (3.32 g, 23.7 mmol) in THF (4 mL) was added. The solution was warmed to 0° C. and cooled back down to -78° C. 1-t-butoxycarbonyl-4-piperidinone (4.69 g, 23.7 mmol) in THF (20 mL) was added. The reaction was warmed to room temp, quenched by addition of solid NH4 Cl, concentrated in vacuo, and partitioned between H2 O (100 mL) and EtOAc (100 mL). The organic layer was washed with H2 O (50 mL) brine (50 mL), dried (MgSO4), and concentrated in vacuo. The resultant oil was heated at 80° C. in t-butanol (50 mL) with potassium t-butoxide (3.4g, 30 mmol) for 2 h. Solid NH4 Cl was added, and the reaction was concentrated in vacuo and partitioned between H2 O (100 mL) and EtOAc (100 mL). The EtOAc was washed with brine (50 mL), dried (MgSO4), concentrated in vacuo and purified by column chromatography (silica gel 60, 0-50percent EtOAc/hexane) to yield 4.47 g (79percent) of the title compound as a crystalline solid. 1 H NMR (400 MHz, DMSO-d6) δ 5.21 (d, 1H), 4.96 (s, 1H), 4.77 (s, 1H), 3.82 (t, 2H), 3.67 (dt, 1H), 2.83 (dt, 1H), 2.77-2.50 (brd d, 1H), 2.26 (dt, 1H), 2.01 (ddd, 1H), 1.38 (s, 9H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With Fe2O<(-)4,5 pinene bipyridine>4(H2O)2(ClO4)4; dihydrogen peroxide at -15℃; for 0.166667h; | |
100% | With lithium hydroxide monohydrate; mesoporous silica; magnesium monoperoxyphthalate hexahydrate In dichloromethane for 1h; Ambient temperature; | |
100% | With air; 1-tert-butylperoxy-1,2-benziodoxol-3(1H)-one In lithium hydroxide monohydrate; acetonitrile at 50℃; for 7.5h; other reagents: 1-hydroxy-1,2-benziodoxol-3(1H)-one, tert-butyl hydroperoxide, 1-(tert-butylperoxy)-5-nitro-1,2-benziodoxol-3(1H)-one, BF3*Et2O presence, galvinoxyl presence, o-iodobenzoic acid presence; |
100% | With tetranitromethane In acetonitrile at -5℃; for 1.5h; Irradiation; | |
100% | With bromine; mesoporous silica In dichloromethane for 1h; Ambient temperature; | |
100% | With CAN; mesoporous silica In dichloromethane for 1h; Ambient temperature; | |
100% | With lithium hydroxide monohydrate; mesoporous silica; pyridinium hydrobromide perbromide In dichloromethane for 0.416667h; | |
100% | With urea hydrogen peroxide addition compound; benzyl aldehyde In ethanol at 20℃; for 2h; | |
100% | With 12-molybdophosphoric acid; urea hydrogen peroxide addition compound In methanol at 20℃; for 0.216667h; chemoselective reaction; | |
100% | With 2-iodyl-3-propoxypyridine In acetonitrile for 1.5h; Reflux; Inert atmosphere; chemoselective reaction; | |
100% | With C12H15MoN3O5; dihydrogen peroxide at 10℃; for 2h; | |
100% | With cyclohexa-1,4-diene; [(N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine)MnIV(O)]2+ In 2,2,2-trifluoroethanol; acetonitrile at 0 - 25℃; | |
100% | With dihydrogen peroxide In neat (no solvent) at 20℃; for 1.33333h; Green chemistry; chemoselective reaction; | General procedure for the oxidation of sulfides to sulfoxides General procedure: To a mixture of sulfide (1 mmol) and 30% H2O2 (0.5 g, 1.2 equiv.), MNPs-PSA (5 mg, 0.95 mol%) was added and the mixture was stirred at room temperature for the time specified. Completion of the reaction was indicated by TLC (n-hexane/ethylacetate 2:1). After completion of the reaction, Et2O (2× 5 mL) was added and the catalyst was separated by an external magnet. The combined organics were washed with brine (5 mL) and dried over anhydrous Na2SO4. The resulting solution was concentrated under reduced pressure to afford the essentially pure products in most cases. Further purification was achieved by short-column chromatography on silica gel with EtOAc/n-hexane as eluent. All the products are known and were characterized by IR, 1H NMR, 13C NMR and by melting point comparisons with those of authentic samples [12-14,25,27]. |
100% | 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 0.0833333h; 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. |
100% | With 1-methyl-4-(trifluoromethyl)pyrimidinium trifluoromethanesulfonate; dihydrogen peroxide In methanol; lithium hydroxide monohydrate at 25℃; for 2h; | |
100% | With C20H18MoN2O7; dihydrogen peroxide In lithium hydroxide monohydrate; acetonitrile at 25℃; for 0.5h; Green chemistry; | |
100% | With C24H32N4O10V2*2CH4O; dihydrogen peroxide In acetonitrile at 25℃; 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. |
100% | With C21H24N2O5V*2C2H6O; dihydrogen peroxide In ethanol at 25℃; for 0.166667h; | 2.6. General homogeneous oxidation procedure for VOL General procedure: Catalytic oxidation was performed in a stirred ask. In a typical experiment, oxo-vanadium(IV)complex (0.01 mmol) was dissolved in ethanol (1 mL). Then substrate (2 mmol) and H2O2(10 mmol) were added to the reaction mixture. The solution was stirred for 10 min at roomtemperature and the reaction products were monitored by gas chromatography. |
100% | With aluminum(III) oxide; tris(2,2′-bipyridyl)ruthenium(II) chloride; oxygen In acetonitrile for 12h; Irradiation; | |
100% | With dihydrogen peroxide In acetonitrile at 25℃; for 1h; | |
100% | With C30H22ClNbO2; dihydrogen peroxide In acetonitrile at 70℃; for 4h; Inert atmosphere; | |
100% | With air; conjugated microporous polymer prepared from 1,3,5-triethynylbenzene with 8-(anthracen-9-yl)-2,2-difluoro-5,11-diiodo-4,6,10,12-tetramethyl-2λ4-boratricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaene In 2-ethoxy-ethanol at 20℃; for 15h; Irradiation; | |
100% | With 9,10-phenanthrenequinone In methanol at 20℃; for 5h; Irradiation; Green chemistry; | |
99% | With tetranitromethane In [D3]acetonitrile at -5℃; for 1.5h; Irradiation; | |
99% | With manganese(IV) oxide; chloro-trimethyl-silane In methanol; lithium hydroxide monohydrate at 20℃; for 1h; | |
99% | With hydrogenchloride; manganese(IV) oxide In methanol at 0 - 10℃; for 0.75h; | |
99% | With phenylphosphonate; dihydrogen peroxide; methyl tri-n-octyl ammonium hydrogen sulfate at 35℃; for 18h; | |
99% | With iron(III) chloride; orthoperiodic acid In acetonitrile at 20℃; for 0.0333333h; | |
99% | With iodosylbenzene; 3,5-disubstituted Cr(salen) In dichloromethane at 20℃; for 2h; | |
99% | With dihydrogen peroxide; phenol at 25℃; for 0.00833333h; | |
99% | With NBS; lithium hydroxide monohydrate; mesoporous silica In dichloromethane at 20℃; for 0.166667h; | |
99% | With oxidovanadium(IV) sulfate; disodium hydrogen phosphite; dihydrogen peroxide In acetonitrile at 20℃; for 1h; | |
99% | With 1-(4-diacetoxyiodobenzyl)-3-methylimidazolium tetrafluoroborate; lithium hydroxide monohydrate at 20℃; for 0.05h; | |
99% | With dihydrogen peroxide; glacial acetic acid In lithium hydroxide monohydrate at 20℃; for 1.33333h; | |
99% | With tert.-butylhydroperoxide In methanol; dichloromethane at 20℃; | |
99% | With NaBrO3; CAN; mesoporous silica In dichloromethane at 20℃; for 0.216667h; | |
99% | With tert.-butylhydroperoxide In methanol; dichloromethane; lithium hydroxide monohydrate at 20℃; for 10h; | |
99% | With HNO3 In acetonitrile at 20℃; for 5h; chemoselective reaction; | |
99% | With Aluminum Chloride; melamine hydrogen peroxide In acetonitrile at 20℃; for 0.67h; chemoselective reaction; | |
99% | With dihydrogen peroxide In methanol; lithium hydroxide monohydrate at 20℃; chemoselective reaction; | |
99% | With dihydrogen peroxide In lithium hydroxide monohydrate at 20℃; for 2h; chemoselective reaction; | |
99% | With dihydrogen peroxide In methanol at 20℃; for 0.333333h; | |
99% | With WO3(3.5 wt%)-ZnO(0.8 wt%)/SnO2; dihydrogen peroxide; carbonic acid dimethyl ester In lithium hydroxide monohydrate at 19.84℃; for 1.5h; chemoselective reaction; | |
99% | With ammonium bromide In lithium hydroxide monohydrate; acetonitrile at 20℃; for 1.5h; | |
99% | With C4H9N2O9W In methanol; lithium hydroxide monohydrate at 20℃; for 0.5h; chemoselective reaction; | General procedure for oxidation of sulfides to sulfoxides: To a stirred solution of sulfide (2.5 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 1:1, in a 50 mL two-necked round-bottomed flask. The resulting reaction mixture was stirred at room temperature. The progress of the reaction was monitored by thin layer chromatography (TLC) and GC. After completion of the reaction, the product as well as unreacted organic substrates were extracted with diethyl ether and dried over anhydrous Na2SO4 and distilled under reduced pressure to remove excess diethyl ether. The corresponding sulfoxide obtained was purified by column chromatography on silica gel using ethyl acetate and n-hexane (1:9). The product was characterized by IR, 1H NMR, 13C NMR spectroscopy and in case of solid samples, by melting point determination. The data were found to be in accordance with the literature (see Supplementary data). |
99% | With polyvinylpolypyrrolidonium tribromide In ethyl acetate at 20℃; for 0.666667h; Green chemistry; | General procedure: In a 25 mL round-bottom flask, to a solutionof sulfide (1 mmol) in ethyl acetate (5 mL), 1.9 gr of polyvinylpolypyrrolidoniume tribromide was added successively and the mixture was stirred magnetically at room temperature for the indicated time in Table 2 (the progress of the reaction monitored by TLC). After completion of the reaction, the pure product was isolated by passing of reaction mixture through a short column using dichlromethane and acetone (95:5) as eluent. The filtrate was evaporated and pure sulfoxides were obtained in good to excellent yields |
99% | With cross-linked poly(N-vinylpyrrolidone):H2O2 complex (1:4.5) In acetonitrile at 70℃; for 3h; | |
99% | With 1,4-bis(3-methylimidazolium-1-yl)butane ditribromide; lithium hydroxide monohydrate In acetonitrile at 25℃; for 0.25h; | |
99% | With dihydrogen peroxide In ethanol at 45℃; for 6h; Green chemistry; chemoselective reaction; | |
99% | With [bis(acetoxy)iodo]benzene; Fe<SUP>III</SUP>(5,10,15-triphenylcorrole trianion)(diethyl ether)<SUB>2</SUB> In deuterated methanol; lithium hydroxide monohydrate at 23℃; for 1h; | 2.3. General procedure for catalytic oxidations General procedure: Unless otherwise specified, all catalytic reactions were typicallycarried out in the presence of a small amount of H2O (4.5 lL) with1 lmol of catalyst (ca. 0.2 mol%) in 2 mL of methanol containing0.5 mmol of organic substrates. PhI(OAc)2 (0.75 mmol, 1.5 equiv.)was then added to the reaction solution at 23 ± 2 C. Aliquots ofthe reaction solution at constant time intervals were analyzed by1H NMR together with GC-MS to determine the conversions,formed products and yields with an internal standard(1,2,4-trichlorobezene). The internal standard was shown to bestable under the oxidation conditions in control reactions. The pureproducts were isolated by a flash column chromatography (silicagel with CH2Cl2 and hexane mixture) to give isolated yields(Table 3, entry 1, 2 and 6). All reactions were performed 2-3 times,and the data reported represents the average of these reactions. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With pyridine; bromine In acetonitrile at -40 - 20℃; | |
80% | With pyridine; bromine In acetonitrile at -40 - 20℃; | |
80% | With pyridine; bromine In acetonitrile at -40 - 20℃; Inert atmosphere; |
73% | With N-Bromosuccinimide; silica gel for 20h; Ambient temperature; | |
49% | With pyridine; bromine In acetonitrile at -40 - 20℃; Inert atmosphere; | 32.2 2) Preparation of bromomethyl phenyl sulfoxide (compound XII); Methyl phenyl sulfoxide (21.644 g, 154.4 mmol) was dissolved in anhydrous pyridine (27.4 mL, 2.2 eq) and dry acetonitrile (100 mL). The solution was cooled to -40°C under an argon atmosphere. A solution of bromine (49.4g, 2eq) in dry acetonitrile (50mL) was added slowly, maintaining the same temperature. The mixture was stirred at - 40°C for lh and then overnight at room temperature. The solvent was evaporated under vacuum and the residue was dissolved in dichloromethane. The organic layer was washed with Na2S203 20%, dried over anhydrous Na2S04 and concentrated to dryness.The crude material was purified by flash column chromatography (ethyl acetate: hexane 20:80) to give 16,989g of yellow oil (yield 49%). |
With pyridine; N-Bromosuccinimide; bromine |
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 |
---|---|---|
93% | With N-chloro-succinimide In dichloromethane at 20℃; | |
91% | With N,N-dichloro-p-toluenesulfonamide In acetonitrile at 20℃; for 0.0833333h; | |
83% | With N-chloro-succinimide In dichloromethane at 20℃; for 48h; | (±)-Chloromethyl phenyl sulfoxide [(±)-14] A solution of (±)-methyl phenyl sulfoxide (22, 3.44g, 24.5 mmol) in CH2Cl2 (100 mL) was treated with NCS (3.28 g, 24.6 mmol) and stirred at rt for 2d. After this time, the reaction mixture was partitioned between CH2Cl2 (10 mL) and H2O (20 mL).The layers were separated and the aqueous phase was extracted with CH2Cl2 (3x15 mL). Thecombined organic phases were washed with H2O (15 mL), brine (15 mL), dried (Na2SO4) andconcentrated in vacuo. The residue was purified by column chromatography (SiO2, eluting with50% EtOAc in hexanes) to afford the racemic chlorosulfoxide (±)-14 (3.57 g, 20.4 mmol, 83%) as acolorless oil. IR and NMR spectral data were in agreement with those previously listed above for(S)-14 |
73% | With N-chloro-succinimide; silica gel for 3h; Ambient temperature; | |
66% | With N-chloro-succinimide In dichloromethane at 20℃; for 25h; | |
With acetyl chloride In dichloromethane at 20℃; for 1h; Cooling with ice; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With N,N-dimethylthioformamide; sulfuric acid In acetone at 30℃; for 3h; | |
100% | With benzo[1,3,2]dioxaborole In hexadeuterobenzene at 20℃; for 150h; | |
99% | With carbon monoxide; 1 wt% Au/TiO2; water monomer In acetone at 60℃; for 5h; Autoclave; |
99% | With 4-Methoxybenzyl alcohol In toluene; acetonitrile at 30℃; for 8h; Schlenk technique; Inert atmosphere; Irradiation; | |
99.8% | With hydrogenchloride; 2,3-dimethyl-2,3-butane diol; H2Mo8O30P(5-)*5H3N*5H(1+)*2H2O In toluene at 60℃; for 24h; | |
98% | With magnesium; mercury (II) chloride In methanol at -43℃; for 5h; | |
98% | With Zinc di(trifluoromethanesulphonate); 4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl-4',4',5',5'-tetramethyl-1,3,2-dioxaborolane In 1,3,5-trimethyl-benzene at 160℃; for 48h; | |
97% | With toluene-4-sulfonic acid; potassium iodide In solid at 30℃; for 4h; | |
97% | With phenylsilane; molybdenum dichloride dioxide In tetrahydrofuran at 67℃; for 2h; | |
97% | With phenylsilane; dimanganese decacarbonyl In neat (no solvent) at 100℃; | |
96% | With t-butyl bromide for 4h; Heating; | |
96% | With B-Br-9-BBN; propylene In dichloromethane 1.) 30 min, -23 deg C, 2.) 10 min, 0 deg C; | |
96% | With sodium tetrahydridoborate; iron(III) chloride In ethanol; water monomer 1.) room temperature, 2 h, 2.) reflux, 5 - 10 min; | |
96% | With N-Bromosuccinimide; 3-mercaptopropionic acid In acetonitrile at 20℃; for 0.166667h; | |
96% | With indium powder; molybdenum pentachloride In tetrahydrofuran at 20℃; for 0.0833333h; | |
96% | With indium powder; tungsten hexachloride In tetrahydrofuran at 20℃; for 0.0833333h; | |
96% | With potassium borohydrate; hafnium tetrachloride In tetrahydrofuran for 12.5h; Inert atmosphere; Reflux; | |
96% | With niobium pentachloride; sodium iodide In acetonitrile at 20℃; for 0.0833333h; | |
96% | With indium powder; niobium pentachloride In tetrahydrofuran at 20℃; for 1h; | |
96% | With hafnium tetrachloride; zinc powder In acetonitrile at 20℃; for 1h; chemoselective reaction; | 4.2. General procedure General procedure: Diphenylsulfoxide (101 mg, 0.5 mmol) and hafnium(IV) chloride (320 mg, 1.0 mmol) were mixed in CH3CN (5 mL) and zinc powder (131 mg, 2.0 mmol) was then added to this solution. The whole mixture was stirred for 3 h at room temperature and the progress of the reaction was followed by TLC. On completion, the solvent was removed under reduced pressure and the residue was extracted successively with ethyl acetate, washed with water and brine. The organic layer was separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by column chromatography on a silica gel (hexane:ethyl acetate = 2:1) to afford diphenylsulfide (88 mg, 95%). All of the products were identified by comparison of their spectroscopic data with authentic samples.[34] |
96% | With iodine; sodium hydrogen sulphite In chloroform at 20℃; for 0.5h; | General procedure: General procedure: A mixture of a sulfoxide (1 mmol), NaHSO3 (1.1 mmol), and I2 (0.025-0.1 mmol) in CHCl3 (1 mL) was stirred at room temperature or at 50 °C. The progress of the reaction was monitored by TLC. After completion, the solution was decanted from the residue, washed with EtOAc (2 x 1 mL). The combined organic layers were concentrated and the residue purified by chromatography on silica gel using n-hexane as eluent. |
96% | With tantalum pentachloride; sodium iodide In acetonitrile at 20℃; for 0.05h; chemoselective reaction; | 4.2. General procedure General procedure: In a 10 mL round-bottom flask, to a solution of diphenylsulfoxide (202 mg, 1.0mmol) in CH3CN (4 mL), tantalum (IV) chloride (179 mg, 0.5 mmol) and sodium iodide (300 mg, 2.0 mmol) were added at room temperature. The mixture turned dark brown almost immediately and the progress of the reaction was followed by TLC. After completion of the reaction (3 min), the reaction mixture was diluted with water and then extracted with ethyl acetate. The combined organic extracts were washed successively with 10% aq Na2S2O3 and H2O. The organic layer was separated and dried over anhydrous Na2SO4 and concentrated under reduced pressure. The resulting crude product was purified through silicagel column chromatography (hexane:ethyl acetate = 2:1) to afford diphenylsulfide (88 mg, 95%). |
95% | With molybdenum pentachloride; zinc powder In tetrahydrofuran at 20℃; for 0.166667h; | |
95% | With sodium tetrahydridoborate; iodine In tetrahydrofuran at 20℃; for 0.0666667h; | |
95% | With indium powder; pivaloyl chloride In isopropanol at 20℃; for 0.2h; | |
95% | With dithiane; bromine In chloroform at 20℃; for 0.166667h; | |
95% | With aluminum(III) oxide; sodium tetrahydridoborate; CoCl2·6H2O; water monomer In hexane at 30℃; for 3h; | |
95% | With Zinc di(trifluoromethanesulphonate); benzo[1,3,2]dioxaborole In toluene at 100℃; for 18h; chemoselective reaction; | |
95% | With sodium iodide In ethanol at 20℃; for 1h; Green chemistry; | General Experimental Procedure for the Deoxygenation of Sulfoxides General procedure: A mixture of diphenyl sulfide (1 mmol), NaI (2.5 mmol), and CSA (0.45 g equalto 2.2 mmol H+) and ethanol (5 mL) was stirred at r.t. for 210 min. The progress of the reaction was monitored by TLC. When the starting sulfoxide had completely disappeared,the mixture was neutralized by adding NaOH solution. The product was extracted withEtOAc (3× 5 mL). The combined extracts were washed with 10% aq Na2S2O3. Theorganic layer dried over MgSO4. The filtrate was evaporated, and then residue was purifiedby column chromatography on silica gel. |
95% | With indium powder; tantalum pentachloride In acetonitrile at 20℃; for 1h; Sonication; chemoselective reaction; | General procedure for the deoxygenation of sulfoxides General procedure: Indium powder (229 mg, 2.0 mmol) and tantalum(V) chloride(358mg, 1.0mmol)weremixed inCH3CN(5 mL). The resultingmixture was sonicated for 0.5 h to produce a solution of the lowvalenttantalum-indium complex. Diphenyl sulfoxide (101 mg,0.5 mmol) was then added to this solution and the reactionmixturewas stirred for 3.0 h at room temperature. The progressof the reaction was followed by TLC. On completion, the solventwas removed under reduced pressure and the residue wasextracted successively with ethyl acetate, washed with water andbrine. The organic layerwas separated and dried over anhydrousNa2SO4. The crude product was purified by column chromatographyon silica gel (hexane:ethyl acetate=2:1) to afford diphenylsulfide (86mg, 92%). All of the productswere identified by comparisonof their spectroscopic data with authentic samples. |
94% | With titanium(IV) tetrachloride; sodium iodide In acetonitrile for 0.0833333h; Ambient temperature; | |
94% | With molybdenium(VI) dioxodichloride; benzo[1,3,2]dioxaborole In tetrahydrofuran; diethyl ether at 67℃; for 0.25h; | |
94% | With methyltrioxorhenium(VII); benzo[1,3,2]dioxaborole In tetrahydrofuran at 20℃; for 0.333333h; | |
94% | With zirconium(IV) oxychloride octahydrate; sodium iodide In water monomer at 90℃; for 1h; chemoselective reaction; | |
94% | With silica bromide In dichloromethane at 20℃; for 0.116667h; Inert atmosphere; | Deoxygenation of diphenyl sulfoxide to diphenylsulfide General procedure: In a typical procedure, diphenyl sulfoxide (2.2 g, 0.01 mol) and brominated silica (18.18 g, 40 mmole Br/g silica) are mixed in an aprotic solvent, e.g. dichloromethane (2 mL) or carbon tetrachloride, at room temperature with exclusion of atmospheric moisture, for 5 min. Diphenyl sulfide is isolated in pure state by simple filtration and evaporation of the solvent (1.84, 99%). |
94% | With hydrogen In neat (no solvent) at 120℃; for 24h; | |
93% | With N,N,N,N,N,N-hexamethylphosphoric triamide; samarium diiodide In tetrahydrofuran at 20℃; for 0.0166667h; | |
93% | With hexamethyldisilathiane In dichloromethane at 60℃; | |
93% | With indium powder; titanium(IV) tetrachloride In tetrahydrofuran at 20℃; for 0.166667h; | |
93% | With chloro-trimethyl-silane; 3-mercaptopropionic acid In acetonitrile at 20℃; for 1h; | |
93% | With silica*PSCl3 In acetonitrile at 20℃; for 4.5h; | |
93% | With ReOBr<SUB>2</SUB>(hmpbta)(PPh<SUB>3</SUB>); 4,4,5,5-tetramethyl-1,3,2-dioxaborolane In tetrahydrofuran for 0.5h; Reflux; chemoselective reaction; | |
93% | With ReOBr2(hmpbta)(PPh3); 4,4,5,5-tetramethyl-1,3,2-dioxaborolane In tetrahydrofuran for 0.25h; Reflux; | |
93% | With bis(2-chlorophenyl)borinic acid; phenylsilane In toluene at 80℃; for 18h; Inert atmosphere; | |
92% | With thexylchloroborane*methyl sulfide In dichloromethane at 0℃; for 0.166667h; | |
92% | With triphenylphosphine In dichloromethane for 1h; Ambient temperature; | |
92% | With triphenylphosphine In dichloromethane for 1h; Ambient temperature; var. aryl and alkyl sulfoxides; | |
92% | With tungsten hexachloride; zinc powder In tetrahydrofuran for 0.0833333h; Ambient temperature; | |
92% | With triphenyl phosphite In acetonitrile for 0.333333h; Heating; | |
92% | With aluminium; nickel (II) chloride In tetrahydrofuran at 20℃; for 0.75h; |
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 |
---|---|---|
With Nitrogen dioxide; ozone In dichloromethane at -10℃; for 2.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 76% 2: 13% | With sodium carbonate In methanol for 16h; Heating; | |
1: 76% 2: 13% | With sodium carbonate In methanol; water for 16h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 81% 2: 9% | With sodium carbonate In methanol for 16h; Heating; | |
1: 81% 2: 9% | With sodium carbonate In 1,2-dimethoxyethane; water for 16h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With iodosylbenzene In acetonitrile at 20℃; for 0.5h; | |
97% | With iodosylbenzene In acetonitrile at 20℃; for 0.5h; | |
86% | With [bis(acetoxy)iodo]benzene; magnesium oxide In dichloromethane at 20℃; for 6h; |
86% | With [bis(acetoxy)iodo]benzene; silver nitrate; 4,4',4-tri-tert-butyl-2,2':6',2-terpyridine In acetonitrile Heating; | |
85% | With iron(II) triflate; iodosylbenzene In acetonitrile at 20℃; for 0.333333h; Molecular sieve; | |
75% | With [bis(acetoxy)iodo]benzene In acetonitrile for 16h; Heating; | |
58% | With iron(III)-acetylacetonate; [bis(trifluoroacetoxy)iodo]-2,3,5,6-tetrafluoro-4-trifluoromethyl-benzene In acetonitrile at 20℃; for 1.5h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 90% 2: 10% | With C38H33BFeN6O3; oxygen-18 In acetonitrile for 8h; | |
70% | With C23H17N7(18)ORu(2+) In acetonitrile at -40℃; Inert atmosphere; | |
1: 70% 2: 30% | With C38H33BFeN6O3; oxygen; <SUP>18</SUP>O-labeled water In acetonitrile for 8h; |
With Fe(TMC)(OTf)2; dihydrogen peroxide; <SUP>18</SUP>O-labeled water In acetonitrile at 10℃; | ||
With bismuth(III) tungsten(VI) oxide; oxygen; <SUP>18</SUP>O-labeled water In acetonitrile at 20℃; for 5h; Irradiation; | Evaluation of photocatalytic activity General procedure: Photocatalytic oxidation of sulfides was carried out in mixedCH3CN and water solvents (2:1 v/v) in suspensions of metalloadedBiVO4 under irradiation by visible light (λ > 420 nm). Aquantity of 0.1 wt.% metal-loaded BiVO4 powder (50 mg) wassuspended in 1.5 mL mixed CH3CN and H216O or H218O solvents(2:1 v/v) including thioanisole (50 lmol). The system was connectedto a balloon filled with pure molecular oxygen. The mixturewas stirred for 30 min to blend evenly in the solution before visiblelight irradiation. The reaction temperature was controlled at 20 °Cby a water-cooling system. The suspensions were irradiated by a300W Xe lamp equipped with a 420 nm cut filter with continuousstirring. After reaction, the mixture was centrifuged at 10,000 rpm for 5 min to remove the catalyst particles. The remaining solutionwas analyzed with an Agilent Gas Chromatograph (GC6890)equipped with a flame ionization detector and an Agilent TechnologyHP-INNOWAX 19091N-213 capillary column using diphenylether as the internal standard. The chemical structures of productswere confirmed by 1H NMR. | |
With oxygen; <SUP>18</SUP>O-labeled water In acetonitrile at 20℃; for 0.5h; Irradiation; | Evaluation of photocatalytic activity General procedure: Photocatalytic oxidation of sulfides was carried out in mixedCH3CN and water solvents (2:1 v/v) in suspensions of metalloadedBiVO4 under irradiation by visible light (λ > 420 nm). Aquantity of 0.1 wt.% metal-loaded BiVO4 powder (50 mg) wassuspended in 1.5 mL mixed CH3CN and H216O or H218O solvents(2:1 v/v) including thioanisole (50 lmol). The system was connectedto a balloon filled with pure molecular oxygen. The mixturewas stirred for 30 min to blend evenly in the solution before visiblelight irradiation. The reaction temperature was controlled at 20 °Cby a water-cooling system. The suspensions were irradiated by a300W Xe lamp equipped with a 420 nm cut filter with continuousstirring. After reaction, the mixture was centrifuged at 10,000 rpm for 5 min to remove the catalyst particles. The remaining solutionwas analyzed with an Agilent Gas Chromatograph (GC6890)equipped with a flame ionization detector and an Agilent TechnologyHP-INNOWAX 19091N-213 capillary column using diphenylether as the internal standard. The chemical structures of productswere confirmed by 1H NMR. | |
With [PPh4][(bTAML)FeIII-OH2]; oxygen-18 In dichloromethane for 0.166667h; | ||
With oxygen; <SUP>18</SUP>O-labeled water In acetonitrile at 20℃; for 2h; Irradiation; chemoselective reaction; | ||
With tetrabutylammonium tetrafluoroborate; <SUP>18</SUP>O-labeled water In N,N-dimethyl-formamide at 25℃; for 10h; Electrochemical reaction; Overall yield = 85 percent; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | Stage #1: racemic methyl phenyl sulfoxide With lithium diisopropyl amide In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: (S)-2-tert-butoxycarbonylamino-3-phenyl-propionic acid methyl ester In tetrahydrofuran; hexane at -78 - 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 94% 2: 6% | With cesium fluoride In tetrahydrofuran Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With [bis(acetoxy)iodo]benzene; silver nitrate; 4,4',4-tri-tert-butyl-2,2':6',2-terpyridine In acetonitrile at 20℃; for 168h; | |
70% | With iron(II) triflate; iodosylbenzene In acetonitrile at 20℃; Molecular sieve; | |
66% | With iodosylbenzene In acetonitrile at 20℃; for 18h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With N-chloro-succinimide In tetrahydrofuran at 20℃; | |
73% | With N-chloro-succinimide In tetrahydrofuran at 0℃; | 2 4.2. Preparation of dichloromethyl phenyl sulfoxide (6) N-Chlorosuccinimide (1.95 g, 14.62 mmol, 2.05 equiv) was added to a solution of methyl phenyl sulfoxide (1.00 g, 7.13 mmol) in THF (15 mL) at 0 °C. The solution was stirred at 0 °C overnight and filtered. The solvent was removed in vacuo and the residue purified by flash column chromatography (4:1 petroleum ether/diethyl ether) to afford the title compound (1.084 g, 73%) as a colourless oil, Rf=0.26 (4:1 petroleum ether/diethyl ether); 1H NMR (400 MHz; CDCl3) δ 7.86-7.74 (2H, m, aromatic CH), 7.68-7.51 (3H, m, aromatic CH) and 6.17 (1H, s, CH); 13C NMR (101 MHz; CDCl3) δ 138.1, 133.2, 129.1, 126.7 and 83.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 3,7,12-triketo-5β-cholan-24-oic acid; (S)-methyl tolyl sulfoxide In diethyl ether; ethyl acetate for 48h; Title compound not separated from byproducts.; | ||
Stage #1: racemic methyl phenyl sulfoxide With (1R,2S)-2-ammonio-1,2-diphenylethanol p-tert-butylbenzoate In hexane for 4h; Stage #2: With Daicel Chiralcel OB-H In hexane; isopropanol Further stages.; | ||
With Chiral HPLC with OD-H column In hexane; isopropanol Resolution of racemate; |
Stage #1: racemic methyl phenyl sulfoxide With (S)-isoleucyl-(S)-2-phenylglycine In methanol at 20℃; Resolution of racemate; Stage #2: With hydrogenchloride In water monomer optical yield given as %ee; | ||
With C4H8O*C168H192Cl8N16O8Zn8*H2O In diethyl ether optical yield given as %ee; | ||
With D-Glucose In aq. phosphate buffer; hexane; isopropanol at 37℃; for 24h; Resolution of racemate; Inert atmosphere; enantioselective reaction; | 2.4 Sequential deracemization of rac-sulfoxide General procedure: Deracemization was performed in a glass vessel containing 10 mL PBS (25 mM, pH 7.4), 1.8 mg glucose and 10 mg sulfoxide. The vessel was sealed with a rubber stopper and nitrogen was flushed inside. The reaction mixture was incubated at 37 °C without agitation for 24 h. After reaction, the solution was extracted with diethyl ether (∼2 mL) and evaporated to dryness. The residue was re-dissolved in hexane/iso-propanol (8/2). The enantiomeric excess (ee) of the separated sulfoxides was determined by HPLC analysis (AGILENT 1100/1200 with a S,S-Whelk-O chiral column (4.6 × 250 mm) and a mobile phase of hexane:iso-propanol (8/2) with a flow rate of 1 mL/min). The detection of the sulfoxides was performed at 254 ± 4 nm. The elution times for sulfoxides and corresponding thioethers were 18.6 min and 23.3 min for (R)- and (S)-methyl phenyl sulfoxide respectively; 19.9 min and 25.7 min for (R)- and (S)-methyl p-tolyl sulfoxide respectively; 25.1 min and 30.3 min for (R)- and (S)-methyl mesityl sulfoxide respectively; 5.6 min for methyl phenyl sulfide; 5.9 min for methyl p-tolyl sulfide; and 6.2 min for methyl mesityl sulfide. It has been noticed that the HPLC chromatograms contained only three peaks, e.g. (R) and (S) enantiomer of rac-sulfoxide, and the corresponding sulfide. | |
With Daicel Chiralcel ODcolumn In hexane; isopropanol Resolution of racemate; | ||
3 % ee | With Gordonia terrae IEGM 136 cells immobilized into polyvinyl alcohol cryogel In water monomer at 28℃; for 24h; Resolution of racemate; 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. |
With Cu-(R)-2,2'-dihydroxy-1,1'-binaphthalene-6,6'-dicarboxylic acid organic framework silica composite In ethanol; hexane Resolution of racemate; | ||
With [Zn(BDA)(bis(4-pyridyl)ethane)]2dimethylacetamide} In hexane; isopropanol Resolution of racemate; | ||
46.8 % ee | With 2C23H18N4*3C8H4O4(2-)*3Zn(2+)*3H2O In methanol at -10℃; for 12h; Resolution of racemate; Sealed tube; | |
83 % ee | With C30H16Br2O10(4-)*3C3H7NO*4H2O*2Cd(2+) In dichloromethane at 20℃; Sealed tube; Resolution of racemate; | |
56 % ee | With recombinant methionine sulfoxide reductase A from Pseudomonas monteilii; thioredoxin In aq. phosphate buffer at 30℃; for 10h; Sealed tube; Resolution of racemate; Green chemistry; Enzymatic reaction; enantioselective reaction; | |
With Cu metal organic framework based on (R)-3,3′-bis(6-carboxy-2-naphthyl)-2,2′-dihydroxy-1,1′-binaphthyl*silica packed stainless steel column (10 cm long × 4.0 mm i.d.) In ethanol at 25℃; Resolution of racemate; | ||
31 % ee | In hexane; isopropanol at 25℃; for 24h; Resolution of racemate; enantioselective reaction; | |
With HPLC column packed amylose 6-(4-methylbenzamido)-6-deoxy-2,3-bis(3,5-dimethylphenylcarbamate) supported on 3-aminopropyl silica gel In hexane; isopropanol at 25℃; Resolution of racemate; enantioselective reaction; | ||
With (R,R)-BINOL2-C/PDAN-based chiral covalent organic frameworks covered silica gel packed HPLC column In hexane; isopropanol at 25℃; Resolution of racemate; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: thionyl chloride; dichloromethane 2: magnesium; iodine; diethyl ether |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
4.47 g (79%) | With diisopropylamine; In tetrahydrofuran; N,N',N''-triethylenephosphoramide; hexane; ethyl acetate; tert-butyl alcohol; | Step 1) 1-t-Butoxycarbonyl-3-hydroxy-4-methylenepiperidine n-Butyl lithium (9.57 mL, 2.45M in hexane, 23.7 mmol) was added to a -78 C. solution of diisopropylamine (3.32 mL, 23.7 mmol) in TEF (15 mL). After 30 min at -78 C., methyl phenyl sulfoxide (3.32 g, 23.7 mmol) in THF (4 mL) was added. The solution was warmed to 0 C. and cooled back down to -78 C. 1-t-butoxycarbonyl-4-piperidinone (4.69 g, 23.7 mmol) in TXF (20 mL) was added. The reaction was warmed to room temp, quenched by addition of solid NH4 Cl, concentrated in vacuo, and partitioned between H2 O (100 mL) and EtOAc (100 mL). The organic layer was washed with H2 O (50 mL) brine (50 mL), dried (MgSO4), and concentrated in vacuo. The resultant oil was heated at 80 C. in t-butanol (50 mL) with potassium t-butoxide (3.4g, 30 mmol) for 2 h. Solid NH4 Cl was added, and the reaction was concentrated in vacuo and partitioned between H2 O (100 mL) and EtOAc (100 mL). The EtOAc was washed with brine (50 mL), dried (MgSO4), concentrated in vacuo and purified by column chromatography (silica gel 60, 0-50% EtOAc/hexane) to yield 4.47 g (79%) of the title compound as a crystalline solid. 1 H NMR (400 MHz, DMSO-d6) delta 5.21 (d,1H), 4.96 (s, 1H), 4.77 (s, 1H), 3.82 (t, 2H), 3.67 (dt, 1H), 2.83 (dt, 1H), 2.77-2.50 (brd d, 1H), 2.26 (dt, 1H), 2.01 (ddd, 1H), 1.38 (s, 9H) ppm. |
4.47 g (79%) | With diisopropylamine; In tetrahydrofuran; hexane; ethyl acetate; tert-butyl alcohol; | Step 1) 1-t-Butoxycarbonyl-3-hydroxy-4-methylenepiperidine n-Butyl lithium (9.57 mL, 2.45M in hexane, 23.7 mmol) was added to a -78 C. solution of diisopropylamine (3.32 mL, 23.7 mmol) in THF (15 mL). After 30 min at -78 C., methyl phenyl sulfoxide (3.32 g, 23.7 mmol) in THF (4 mL) was added. The solution was warmed to 0 C. and cooled back down to -78 C. 1-t-butoxycarbonyl-4-piperidinone (4.69 g, 23.7 mmol) in THF (20 mL) was added. The reaction was warmed to room temp, quenched by addition of solid NH4 Cl, concentrated in vacuo, and partitioned between H2 O (100 mL) and EtOAc (100 mL). The organic layer was washed with H2 O (50 mL) brine (50 mL), dried (MgSO4), and concentrated in vacuo. The resultant oil was heated at 80 C. in t-butanol (50 mL) with potassium t-butoxide (3.4g, 30 mmol) for 2 h. Solid NH4 Cl was added, and the reaction was concentrated in vacuo and partitioned between H2 O (100 mL) and EtOAc (100 mL). The EtOAc was washed with brine (50 mL), dried (MgSO4), concentrated in vacuo and purified by column chromatography (silica gel 60, 0-50% EtOAc/hexane) to yield 4.47 g (79%) of the title compound as a crystalline solid. 1 H NMR (400 MHz, DMSO-d6) delta 5.21 (d, 1H), 4.96 (s, 1H), 4.77 (s, 1H), 3.82 (t, 2H), 3.67 (dt, 1H), 2.83 (dt, 1H), 2.77-2.50 (brd d, 1H), 2.26 (dt, 1H), 2.01 (ddd, 1H), 1.38 (s, 9H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80-85 | inert atmosphere;; | |
In methanol excess sulfoxide, slight excess NH4PF6, 60°C, 6 h; removal of volatiles (vac.), extn. into CH2Cl2, filtration, partial evapn., pptn. on Et2O addn.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With 2-iodoxybenzoic acid In chloroform; water at 20℃; for 0.5h; | 1.1 Example 1N-[(4-methoxyphenyl)(methyl)oxo-λ6-sulfanylidene]-5-(phenylethynyl)nicotinamideStep 1 - Representative procedure for the preparation of sulfoxides Methyl phenyl sulfoxide To a stirred suspension of iodoxybenzoic acid (3.7 g, 13.2 mmol, 1.1 eq) in 100:1 CHCI3/H2O (25 mL) was added tetraethylammonium bromide (TEAB) (126 mg, 5 mol%), followed by the addition of/?-tolyl sulfide (1.66 g, 12 mmol) in one portion. The mixture was stirred at room temperature for approximately 30 minutes until consumption of sulfide was observed (TLC, hexanes/EtOAc 1/1). The residual solids were removed by filtration and washed with CHCI3 (40 mL). The combined filtrate was washed successively with saturated aq. NaHCO3 (30 mL), saturated aq. NaCl (30 mL), dried over sodium sulfate, and concentrated to provide the crude product. Purification by silica gel column chromatography (50% hexanes/EtOAc elution) afforded the title compound (1.68 g, yield 91%). 1H NMR (300 MHz, CDCl3) δ 7.52 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 2.71 (s, 3H), 2.42 (s, 3H); ESI-MS m/z 154.7 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With lithium diisopropyl amide In tetrahydrofuran at -75 - 23℃; | |
80% | Stage #1: racemic methyl phenyl sulfoxide With n-butyllithium; diisopropylamine In tetrahydrofuran; hexanes at -75 - 5℃; Inert atmosphere; Stage #2: N-tert-butyloxycarbonylpiperidin-4-one In tetrahydrofuran; hexanes at -75 - 20℃; for 18h; Inert atmosphere; Stage #3: With water; ammonium chloride In tetrahydrofuran; hexanes | 1.A A solution of n-butyllithium (96 mL of 2.5 M in hexanes, 0.240 mol) was added dropwise at -750C to a solution of diisopropylamine (33.2 mL, 0.237 mol) in THF (150 mL) with mechanical stirring under argon and stirred for 30 min. To this solution was added a solution of (+/-)-methyl phenyl sulfoxide (33.2 g, 0.237 mol) in THF (40 mL) dropwise over 15 min at -750C. The reaction mixture was quickly warmed to 5 0C, stirred for 20 min, cooled back down to -75 0C, treated with a solution of 1-Boc-4-piperidone (46.9 g, 0.235 mol; CASNo. 79099-07-3) in THF (200 mL) and slowly warmed to room temperature over 18 h. The resulting light yellow suspension was quenched by the addition of solid ammonium chloride (39 g, 0.729 mol) and concentrated in vacuo. The residue was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc (2x) and the combined EtOAc extracts were washed with brine (2x), dried (MgSO4), filtered and concentrated in vacuo to afford 1a (64.3 g, 80%) as an off- white solid: 1H NMR (CDCI3) δ 7.70-7.50 (m, 5H), 4.20 (br s, 1H), 4.05-3.80 (m, 2H), 3.40-3.15 (m, 2H), 3.06, 2.70 (AB9, Jab = 13.4 Hz, 2H), 2.19-2.13 (m, 1H), 1.88-1.50 (m, 3H), 1.46 (s, 9H); MS (ES) m/z 340.2 (MH)+. |
With lithium diisopropyl amide In tetrahydrofuran at -75 - 23℃; for 18h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | Stage #1: racemic methyl phenyl sulfoxide With trifluoroacetic anhydride In dichloromethane at -78℃; for 0.5h; Stage #2: indole In dichloromethane at -78℃; for 0.5h; Stage #3: With triethylamine In dichloromethane at 20℃; for 96h; | 1 EXAMPLE 1; Preparation of 3-(Phenylthio)-1H-indole [0171] A solution of methyl phenyl sulfoxide (4.0 g, 147 mmol) in CH2Cl2 is cooled to -78° C., treated dropwise with trifluoroacetic anhydride (4.0 mL, 5.99 g, 28.5 mmol), stirred for 30 min at -78° C., treated with a solution of indole (1.82 g, 15.6 mmol) in CH2Cl2, stirred for 30 min at -78° C., treated with triethylamine (20 mL, 145 mmol), stirred for 4 days at ambient temperatures and diluted with water. The phases are separated. The organic phase is dried over MgSO4 and concentrated in vacuo. The resultant residue is chromatographed (1:99 methanol:CH2Cl2) to give the title product as a white solid, 3.08 g (88% yield), mp 149-151° C., characterized by mass spectral and HNMR analyses. |
88% | Stage #1: racemic methyl phenyl sulfoxide With trifluoroacetic anhydride In dichloromethane at -78℃; for 0.5h; Stage #2: indole In dichloromethane at -78℃; for 0.5h; Stage #3: With triethylamine In dichloromethane at 20℃; for 96h; | 1 EXAMPLE 1 Preparation of 3-(Phenylthio)-1H-indole EXAMPLE 1 Preparation of 3-(Phenylthio)-1H-indole A solution of methyl phenyl sulfoxide (4.0 g, 147 mmol) in CH2Cl2 is cooled to -78° C., treated dropwise with trifluoroacetic anhydride (4.0 ML, 5.99 g, 28.5 mmol), stirred for 30 min at -78° C., treated with a solution of indole (1.82 g, 15.6 mmol) in CH2Cl2, stirred for 30 min at -78° C., treated with triethylamine (20 ML, 145 mmol), stirred for 4 days at ambient temperatures and diluted with water.The phases are separated.The organic phase is dried over MgSO4 and concentrated in vacuo.The resultant residue is chromatographed (1:99 methanol:CH2Cl2) to give the title product as a white solid, 3.08 g (88% yield), mp 149-151° C., characterized by mass spectral and HNMR analyses. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.67% | In diethyl ether at 0 - 5℃; Inert atmosphere; | 2 Example 2Preparation of S-methyl-S-phenyl-2 ,3,4, 5-tetramethyl phenyl sulfonium triflata Methyl phenyl sulfoxide (9.45 g, 67.40 mmol) was dissolved in dry diethyl ether (50 ml) under nitrogen atmosphere. 1,2,3,4- Tetramethylbenzene (10.1 mL, 1.0 eq) was added to the previous solution and then the mixture was cooled to a temperature between 5 °C and 0 °C. After stabilizing the temperature, trifluoromethanesulfonic anhydride (11.36 mL, 1.0 eq) was added slowly, maintaining the same temperature. The mixture was stirred until the reaction was complete. The precipitated triflate salt was isolated by filtration, washed with diethyl ether at 0 °C dried. 22.26 g of the desired product was obtained as a white solid (Yield: 93.67%); .p. : 136-137 °C; XH NMR (solvent CDC13, 400 MHz): δ 7.78-7.77 (2H, m) , 7.65-7.59 (3H, m), 7.50 (1H, s), 3.61 (3H, s) , 2.48 (3H, s) , 2.39 (3H, s), 2.27 (3H, s), 2.26 (3H, s) . 13C NMR (CDCI3, 100 MHz): δ 143.1, 138.8, 138.5, 136.1, 133.8, 131.3, 129.4, 126.7, 126.1, 119.9, 28.5, 20.9, 17.3, 16.8, 16.7. FT-IR (KBr) : 3014, 2931, 1477, 1448, 1265, 1224, 1149, 1031 cm-1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With (1S)-10-camphorsulfonic acid In dichloromethane at 25℃; for 1h; diastereoselective reaction; | 4.2 Representative procedure for acid-catalyzed sulfamination (Table 1, entry 2) General procedure: To a stirred solution of benzenesulfenate (2) (0.084 g, 0.60 mmol) and alkene 1b (0.155 g, 0.50 mmol) in CH2Cl2 (2.5 mL) was added CSA (0.012 g, 0.05 mmol) at 25 °C. Upon stirring at 25 °C for 1 h, the reaction mixture was filtered through a plug of silica gel with CH2Cl2 as eluent, concentrated, and purified by column chromatography (silica gel, eluent: petroleum ether/ethyl acetate=40:1) to give compound 3b as white solid (0.199 g, 95%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With (1S)-10-camphorsulfonic acid In dichloromethane at 25℃; for 1h; diastereoselective reaction; | 4.2 Representative procedure for acid-catalyzed sulfamination (Table 1, entry 2) General procedure: To a stirred solution of benzenesulfenate (2) (0.084 g, 0.60 mmol) and alkene 1b (0.155 g, 0.50 mmol) in CH2Cl2 (2.5 mL) was added CSA (0.012 g, 0.05 mmol) at 25 °C. Upon stirring at 25 °C for 1 h, the reaction mixture was filtered through a plug of silica gel with CH2Cl2 as eluent, concentrated, and purified by column chromatography (silica gel, eluent: petroleum ether/ethyl acetate=40:1) to give compound 3b as white solid (0.199 g, 95%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With (1S)-10-camphorsulfonic acid In dichloromethane at 25℃; for 1h; diastereoselective reaction; | 4.2 Representative procedure for acid-catalyzed sulfamination (Table 1, entry 2) General procedure: To a stirred solution of benzenesulfenate (2) (0.084 g, 0.60 mmol) and alkene 1b (0.155 g, 0.50 mmol) in CH2Cl2 (2.5 mL) was added CSA (0.012 g, 0.05 mmol) at 25 °C. Upon stirring at 25 °C for 1 h, the reaction mixture was filtered through a plug of silica gel with CH2Cl2 as eluent, concentrated, and purified by column chromatography (silica gel, eluent: petroleum ether/ethyl acetate=40:1) to give compound 3b as white solid (0.199 g, 95%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With trifluorormethanesulfonic acid; (1S)-10-camphorsulfonic acid In dichloromethane at 25℃; for 1h; diastereoselective reaction; | 4.2 Representative procedure for acid-catalyzed sulfamination (Table 1, entry 2) General procedure: To a stirred solution of benzenesulfenate (2) (0.084 g, 0.60 mmol) and alkene 1b (0.155 g, 0.50 mmol) in CH2Cl2 (2.5 mL) was added CSA (0.012 g, 0.05 mmol) at 25 °C. Upon stirring at 25 °C for 1 h, the reaction mixture was filtered through a plug of silica gel with CH2Cl2 as eluent, concentrated, and purified by column chromatography (silica gel, eluent: petroleum ether/ethyl acetate=40:1) to give compound 3b as white solid (0.199 g, 95%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With trifluorormethanesulfonic acid; (1S)-10-camphorsulfonic acid In dichloromethane at 25℃; for 1h; diastereoselective reaction; | 4.2 Representative procedure for acid-catalyzed sulfamination (Table 1, entry 2) General procedure: To a stirred solution of benzenesulfenate (2) (0.084 g, 0.60 mmol) and alkene 1b (0.155 g, 0.50 mmol) in CH2Cl2 (2.5 mL) was added CSA (0.012 g, 0.05 mmol) at 25 °C. Upon stirring at 25 °C for 1 h, the reaction mixture was filtered through a plug of silica gel with CH2Cl2 as eluent, concentrated, and purified by column chromatography (silica gel, eluent: petroleum ether/ethyl acetate=40:1) to give compound 3b as white solid (0.199 g, 95%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With (1S)-10-camphorsulfonic acid; p-toluenesulfonic acid monohydrate In dichloromethane at 25℃; for 12h; diastereoselective reaction; | 4.2 Representative procedure for acid-catalyzed sulfamination (Table 1, entry 2) General procedure: To a stirred solution of benzenesulfenate (2) (0.084 g, 0.60 mmol) and alkene 1b (0.155 g, 0.50 mmol) in CH2Cl2 (2.5 mL) was added CSA (0.012 g, 0.05 mmol) at 25 °C. Upon stirring at 25 °C for 1 h, the reaction mixture was filtered through a plug of silica gel with CH2Cl2 as eluent, concentrated, and purified by column chromatography (silica gel, eluent: petroleum ether/ethyl acetate=40:1) to give compound 3b as white solid (0.199 g, 95%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With (1S)-10-camphorsulfonic acid; p-toluenesulfonic acid monohydrate In dichloromethane at 25℃; for 12h; diastereoselective reaction; | 4.2 Representative procedure for acid-catalyzed sulfamination (Table 1, entry 2) General procedure: To a stirred solution of benzenesulfenate (2) (0.084 g, 0.60 mmol) and alkene 1b (0.155 g, 0.50 mmol) in CH2Cl2 (2.5 mL) was added CSA (0.012 g, 0.05 mmol) at 25 °C. Upon stirring at 25 °C for 1 h, the reaction mixture was filtered through a plug of silica gel with CH2Cl2 as eluent, concentrated, and purified by column chromatography (silica gel, eluent: petroleum ether/ethyl acetate=40:1) to give compound 3b as white solid (0.199 g, 95%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With (1S)-10-camphorsulfonic acid In dichloromethane at 25℃; for 12h; diastereoselective reaction; | 4.2 Representative procedure for acid-catalyzed sulfamination (Table 1, entry 2) General procedure: To a stirred solution of benzenesulfenate (2) (0.084 g, 0.60 mmol) and alkene 1b (0.155 g, 0.50 mmol) in CH2Cl2 (2.5 mL) was added CSA (0.012 g, 0.05 mmol) at 25 °C. Upon stirring at 25 °C for 1 h, the reaction mixture was filtered through a plug of silica gel with CH2Cl2 as eluent, concentrated, and purified by column chromatography (silica gel, eluent: petroleum ether/ethyl acetate=40:1) to give compound 3b as white solid (0.199 g, 95%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 77% 2: 23% | With [VVO(hap-dahp)]-Y In water; acetonitrile at 20℃; Overall yield = 98 %; | 2.4.2 Oxidation of methyl phenyl sulfide and diphenyl sulfide Methyl phenyl sulfide (1.24g, 10mmol) or diphenyl sulfide (1.86g, 10mmol), 30% aqueous H2O2 (1.14g, 10mmol) and catalyst (0.0075g) in acetonitrile were stirred at room temperature and the reaction was monitored by withdrawing samples at different time intervals and analyzing them quantitatively by gas chromatography. The identities of the products were confirmed as mentioned above. |
With [2-methylpiperazinium]0.5[vanadium(III)(H2O)(HPO3)2] In acetonitrile at 25℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With tris-(dibenzylideneacetone)dipalladium(0); cyclopentyl methyl ether; sodium t-butanolate; nixantphos at 110℃; for 12h; Inert atmosphere; | |
82% | With C16H18N4*2BrH; bis(dibenzylideneacetone)-palladium(0); lithium tert-butoxide In toluene at 110℃; for 24h; | |
62% | With (chloro)phenylallyl[1,3‐bis(2,6‐bis(diphenylmethyl)‐4‐methylphenyl)imidazo‐2‐ylidene]palladium(II); potassium 2-methylbutan-2-olate In 1,4-dioxane at 110℃; for 20h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate; silver carbonate In chlorobenzene at 120℃; for 6h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.67% | In diethyl ether at 0 - 5℃; Inert atmosphere; | 2 Preparation of S-methyl-S-phenyl-2,3,4,5-tetramethyl phenyl sulfonium triflate Example 2 Preparation of S-methyl-S-phenyl-2,3,4,5-tetramethyl phenyl sulfonium triflate Methyl phenyl sulfoxide (9.45 g, 67.40 mmol) was dissolved in dry diethyl ether (50 ml) under nitrogen atmosphere. 1,2,3,4-Tetramethylbenzene (10.1 mL, 1.0 eq) was added to the previous solution and then the mixture was cooled to a temperature between 5° C. and 0° C. After stabilizing the temperature, trifluoromethanesulfonic anhydride (11.36 mL, 1.0 eq) was added slowly, maintaining the same temperature. The mixture was stirred until the reaction was complete. The precipitated triflate salt was isolated by filtration, washed with diethyl ether at 0° C. dried. 22.26 g of the desired product was obtained as a white solid (Yield: 93.67%); m.p.: 136-137° C.; 1H NMR (solvent CDCl3, 400 MHz): δ 7.78-7.77 (2H, m), 7.65-7.59 (3H, m), 7.50 (1H, s), 3.61 (3H, s); 2.48 (3H, s), 2.39 (3H, s), 2.27 (3H, s), 2.26 (3H, s). 13C NMR (CDCl3, 100 MHz): δ 143.1, 138.8, 138.5, 136.1, 133.8, 131.3, 129.4, 126.7, 126.1, 119.9, 28.5, 20.9, 17.3, 16.8, 16.7. FT-IR (KBr): 3014, 2931, 1477, 1448, 1265, 1224, 1149, 1031 cm-1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91.7% | With C27H15Cl3FeN3O3; dihydrogen peroxide In water at 18℃; for 8h; | 2.3. General procedure for oxygenation of organic compounds General procedure: 30% Aqueous H2O2 solution (0.5-4mmol) was added to a stirred mixture of acetonitrile (MeCN, 3ml), substrate (1mmol) and catalyst Q3FeIII (0.01mmol) and then the reaction mixture was stirred magnetically at 12-35°C. After the desired reaction time had elapsed, the addition of MnO2 decomposed the residual H2O2 and the solid residue was filtrated from the reaction solution, the resulting filtrate was subjected to an analysis of the oxygenated products. The content of various oxygenated products was measured on an Agilent 6890N gas chromatography with a DB-17 polysiloxane capillary column (30m×0.32mm×0.50μm) and flame ionization detector (FID) using n-hexanol as an internal standard. Both the injector and detector temperature were 250°C, and the column temperature was 80-120°C. Each experiment was conducted in triplicate, the data deviation between three parallel experiments was lower than ca. 5%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With 2,6-dimethylpyridine; trifluoromethylsulfonic anhydride In dichloromethane at -78 - 65℃; for 16h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: dichloromethane / 3.25 h / -30 - -20 °C / Inert atmosphere 2: 1,8-diazabicyclo[5.4.0]undec-7-ene / dichloromethane / 2 h / -20 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | Stage #1: racemic methyl phenyl sulfoxide With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78℃; for 0.5h; Inert atmosphere; Stage #2: ethyl-2-picolinate In hexane; ethyl acetate at -78℃; for 0.5h; Inert atmosphere; | 1. Chemistry. Synthesis of -ketosulfoxides. General Procedure General procedure: A freshly prepared solution of LDA (6.46 mmol, 2 eq.) in THF fromdiisopropylamine (7.11 mmol, 2.2 eq.) in THF (10 mL) at -78 °C and 2 M de nBuLi solution in hexane (3.23 mL, 6.46 mmol, 2 eq.), is added over the corresponding methyl sulfoxide (3.23 mmol, 1 eq.) in THF (10 mL), at -78°C, under argon. After stirring for 30 min. the formed carbanion solution is added over a THF solution (10 mL) of the corresponding ethyl carboxylate (3.23 mmol, 1 eq.), at -78°C, under argon. After stirring for 30 min., the reaction mixture was quenched with saturated NH4Cl, aqueous solution and 1M H2SO4 was added until pH 3-4. The aqueous phase was then extracted with EtOAc (5 x 50 mL), washed with saturated NaHCO3 aqueous solution and saturated NaCl aqueous solution, and dried over Na2SO4. After removing the solvent at vacuo, the residue was purified by flash chromatography, to give the corresponding -ketosulfoxide. |
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 |
---|---|---|
73% | Stage #1: racemic methyl phenyl sulfoxide With diisopropylaminomagnesium chloride lithium chloride In tetrahydrofuran at 0℃; for 1h; Inert atmosphere; Stage #2: phenylmagnesium bromide In tetrahydrofuran; diethyl ether at 65℃; for 14h; | I.1. Two-step synthesis of benzyl(phenyl)sulfide (1b) General procedure: Step 1: The preparation was adapted from the procedure reported by Kakarla and co-workers,[5] as follows: to a solution of thioanisole 1a (0.3 mmol, 1.0 equiv.), silica gel (0.99 mmol, 3.33 equiv) and acetic anhydride (0.36 mmol, 1.2 equiv.) in DCM (5 mL) stirred at r.t., hydrogen peroxide (0.33 mmol,30% w/w solution in water, 1.1 equiv.) was added. The resulting mixture was stirred at r.t. for 24 h,then filtered, diluted in water and extracted with DCM. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude mixture could be purified by column chromatography (DCM, Rf = 0.15) to obtain pure 2a (39 mg, 92% yield) as acolorless oil whose characterization data were in accordance with reported literature.[6]Step 2: The previously reported procedure [4] was followed: to a solution of 2a (39 mg, 0.28 mmol, 1.0equiv.) in anhydrous THF (2.4 mL) stirred at 0°C under Ar, a solution of DIPAMgCl·LiCl (0.52 mL of a0.58 M solution in THF, 0.31 mmol, 1.1 equiv.) was added dropwise. The resulting pale yellow solution was stirred at 0 °C for 1 h, then phenylmagnesium bromide (0.15 mL of a 2 M solution inEt2O, 0.29 mmol, 1.05 equiv.) was added dropwise. The resulting dark yellow solution was heated to 65°C and stirred for 14 h. The reaction was quenched with saturated aqueous NH4Cl (1 mL). The crude mixture was extracted with Et2O (3 x 1 mL), and the combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo, affording a crude mixture that was analyzed by 1H-NMR(using 1,1,2,2-tetrachloroethane as internal standard), detecting thioether 1b in 73% yield. |
71% | Stage #1: racemic methyl phenyl sulfoxide With diisopropylaminomagnesium chloride lithium chloride In tetrahydrofuran at 0℃; for 1h; Inert atmosphere; Stage #2: phenylmagnesium bromide In tetrahydrofuran; diethyl ether at 0 - 65℃; for 14h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 99% 2: 98% | Stage #1: 1-dodecyne; 1,1'-sulfinylbisbenzene With dichloro-[1,3-bis(2,6-diisopropylpenyl)-2-imidazolidinyliden]-(3-chloropyridyl)palladium(II); lithium tert-butoxide In tetrahydrofuran at 70℃; for 6h; Schlenk technique; Inert atmosphere; Stage #2: With methyl iodide In tetrahydrofuran at 20℃; for 2h; Schlenk technique; Inert atmosphere; | Procedure for electrophilic trap of the sulfur-containing fragments (Scheme 2) An oven-dried Schlenk tube was charged with diphenyl sulfoxide (1a, 61 mg, 0.30 mmol),1-dodecyne (2a, 60 mg, 0.36 mmol), Pd-PEPPSI-SIPr (5.1 mg, 0.0075 mmol), LiOtBu (36mg, 0.45 mmol), and THF (1.5 mL). The resulting mixture was stirred at 70 °C for 6 h.Iodomethane (0.050 mL, 0.80 mmol) was added and the resulting mixture was additionallystirred at room temperature for 2 h. Then, the mixture was passed through pads of anhydrousNa2SO4, activated alumina, and silica gel with Et2O as an eluent. The ethereal solution wasconcentrated under reduced pressure. The yields of 3aa and 1j were determined by 1H NMRusing dibromomethane as an internal standard. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: lithium diisopropyl amide / tetrahydrofuran / 1 h / -78 °C / Inert atmosphere 1.2: 80 °C 2.1: manganese(IV) oxide; (tris(6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octadionato))ytterbium(III) / dichloromethane / 20 °C / Inert atmosphere 3.1: hydroxylamine hydrochloride / acetonitrile / Reflux 4.1: pyridine / dichloromethane | ||
Multi-step reaction with 4 steps 1.1: lithium diisopropyl amide / tetrahydrofuran / 1 h / -78 °C / Inert atmosphere 1.2: 80 °C 2.1: manganese(IV) oxide; (tris(6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octadionato))ytterbium(III) / dichloromethane / 20 °C / Inert atmosphere 3.1: pyridine / dichloromethane 4.1: hydroxylamine hydrochloride / acetonitrile |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | Stage #1: racemic methyl phenyl sulfoxide With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 1h; Inert atmosphere; Stage #2: 16-dehydropregnenolone acetate With potassium <i>tert</i>-butylate In <i>tert</i>-butyl alcohol at 80℃; | 1 Example 1 Synthesis of Intermediate 3 Methylphenylsulfoxide (1.42 g, 10.1 mmol) and tetrahydrofuran solution were added to a round bottom flask and the reaction was cooled to -78 ° C. Under argon,LDA (5.05 mL, 10.1 mmol) was slowly added to the reaction flask,The reaction was stirred for 1 hour. Compound 2 (2.0 g, 0.561 mmol) was added to the reaction flask,Thin layer chromatography monitoring. After the reaction is completed, the saturated ammonium chloride solution is quenched.Extracted with ether, dried over anhydrous magnesium sulfate and evaporated to dryness under reduced pressure.The residue was dissolved in t-butanol, potassium tert-butoxide (3.15 g, 28.1 mmol)Heated to 80 ° C reflux, TLC detection. Until the reaction is completed,Quenched with saturated ammonium chloride solution, extracted with ether, dried over anhydrous magnesium sulfate, evaporated to dryness under reduced pressure,The residue was subjected to column chromatography (petroleum ether / ethyl acetate = 4: 1 → 2: 1)Isolated and purified to give 1.60 g of compound 3 with a yield of 86%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | Stage #1: N-aminophthalamide With 2-iodoxybenzoic acid; scandium tris(trifluoromethanesulfonate) In ethyl acetate at 20℃; for 0.166667h; Inert atmosphere; Stage #2: racemic methyl phenyl sulfoxide In ethyl acetate for 21h; Inert atmosphere; Reflux; | General Procedure for Sulfoximination of Sulfoxides General procedure: Sc(OTf)3 (0.075 mmol) was added to the suspension of IBX (0.75 mmol) and PhthNH2 (0.8mmol) in EA (4 mL) under nitrogen atmosphere. After stirring 10 min at rt, sulfoxide (1 mmol) was added. The RM was strirred at reflux for 3 h, allowed to reach rt. IBX (0.75 mmol) and PhthNH2 (0.8 mmol) were added to RM and strirred at reflux for 5h, allowed to reach rt. IBX(0.75 mmol) and PhthNH2 (0.8 mmol) were added to RM and strirred at reflux for 13h, allowed to reach rt. The RM was quenched with saturated solution of Na2CO3. The separated organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel using Hexane: EA (2.5:1) to afford sulfoximine. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | Stage #1: 2-fluoro-4-methylpyridine; racemic methyl phenyl sulfoxide With trifluoromethylsulfonic anhydride In dichloromethane at -43 - 20℃; for 10h; Schlenk technique; Stage #2: With water; sodium hydrogencarbonate at 20℃; for 0.166667h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With 1,1-Diphenylethylene; bis(triethylphosphine)nickel(II) bromide In tetrahydrofuran at 80℃; for 12h; Schlenk technique; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 0.45 mmol 2: 0.31 mmol 3: 0.13 mmol | Stage #1: racemic methyl phenyl sulfoxide; (dimethyl(phenyl)silyl)zinc chloride With bis(triethylphosphine)nickel(II) bromide In tetrahydrofuran at 80℃; for 0.0833333h; Schlenk technique; Inert atmosphere; Stage #2: In tetrahydrofuran at 80℃; for 0.5h; Schlenk technique; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With iodine; N-ethyl-N,N-diisopropylamine In acetonitrile at 105℃; for 8h; | 1 General procedure: In an 8mL reaction flask, add ethyl propiolate (1.0mmol),Diisopropylethylamine (0.1 mmol), elemental iodine (0.6 mmol), methyl aryl sulfoxide (2.0 mmol) and acetonitrile (2.0 mL).The resulting mixture was stirred and reacted at 105°C., and the progress of the reaction was monitored by thin-layer chromatography. The reaction time was 8 hours.After the reaction is over, add 10ml of water to the reaction mixture, and extract with ethyl acetate (5ml×2), combine the organic phases and wash with saturated brine, dry, concentrate in vacuo and purify by column chromatography to obtain the target compound . |
57% | With hydrogen iodide In water at 105℃; for 8h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With trifluorormethanesulfonic acid In ethyl acetate at 20℃; | 2.3 (3) Synthesis of 1-phenyl-4-(2-(phenylthio)methyl)butane-1,3-dione: Add 10ml of ethyl acetate (EA), 4-phenyl-3-butyn-1-one (1.44g, 0.01mol), phenylmethyl sulfoxide (1.27g, 0.01mol), trifluoromethane into the single-mouth flask 0.1ml of sulfonic acid, stirred at room temperature for 3h, check the reaction, after the reaction is complete, add 1mL of 2N sodium hydroxide solution, and extract with ethyl acetate (10mL×3), combine the organic phases, wash with 10mL of water, dry with anhydrous sodium sulfate, and filter. The filtrate was concentrated under reduced pressure and purified by column chromatography [v (petroleum ether): v (ethyl acetate) = 20:1] to obtain 2.56 g of compound 3f' as a pale yellow oil, with a yield of 90%. |
89% | With trifluorormethanesulfonic acid In ethyl acetate at 20℃; for 4h; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | Stage #1: racemic methyl phenyl sulfoxide With oxalyl dichloride In acetonitrile at 0℃; Reflux; Stage #2: (E)-4-(p-bromophenyl)but-3-enoic acid In acetonitrile for 10h; Reflux; | General Procedure for arylsulfenylation of unsaturated acids with PhSOCH3 and (COCl)2 in CH3CN. General procedure: To a solution of ArSOCH3 (15 mmol, 3 equivalents) in acetonitrile cooled at 0 °C was addeddropwise a solution of oxalyl chloride (3.75 mmol, 0.75 equivalents) in acetonitrile (10 mL). Themixture was stirred for 10 min at 0 °C. It was then allowed to warm to room temperature and heatedto reflux. Then an unsaturated acid (1a-w) (5 mmol, 1 equivalent) was added and the reactionmixture continued to reflux for 10 h. After cooling to room temperature, the reaction mixture wasthen concentrated on a rotary evaporator and the residue redissolved in CH2Cl2 (100 mL). Theresulting solution was washed with saturated NaHCO3 and brine. The organic phase was dried oversodium sulfate, filtered, concentrated, and the residue purified by flash chromatography on silicagel column to give the arylsulfenylation lactones. (2a-z). The products 2a-w were obtained usingPhSOCH3 and 2x-z obtained using methyl p-methylphenyl sulfoxide, methyl p-fluorophenylsulfoxide, and methyl p-chlorophenyl sulfoxide respectively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | Stage #1: racemic methyl phenyl sulfoxide With oxalyl dichloride In acetonitrile at 0℃; Reflux; Stage #2: 2,2-dimethylpent-4-enoic acid In acetonitrile for 10h; Reflux; | General Procedure for arylsulfenylation of unsaturated acids with PhSOCH3 and (COCl)2 in CH3CN. General procedure: To a solution of ArSOCH3 (15 mmol, 3 equivalents) in acetonitrile cooled at 0 °C was addeddropwise a solution of oxalyl chloride (3.75 mmol, 0.75 equivalents) in acetonitrile (10 mL). Themixture was stirred for 10 min at 0 °C. It was then allowed to warm to room temperature and heatedto reflux. Then an unsaturated acid (1a-w) (5 mmol, 1 equivalent) was added and the reactionmixture continued to reflux for 10 h. After cooling to room temperature, the reaction mixture wasthen concentrated on a rotary evaporator and the residue redissolved in CH2Cl2 (100 mL). Theresulting solution was washed with saturated NaHCO3 and brine. The organic phase was dried oversodium sulfate, filtered, concentrated, and the residue purified by flash chromatography on silicagel column to give the arylsulfenylation lactones. (2a-z). The products 2a-w were obtained usingPhSOCH3 and 2x-z obtained using methyl p-methylphenyl sulfoxide, methyl p-fluorophenylsulfoxide, and methyl p-chlorophenyl sulfoxide respectively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
17.647 % de | Stage #1: racemic methyl phenyl sulfoxide With oxalyl dichloride In acetonitrile at 0℃; Reflux; Stage #2: (+-)-2-methyl-pent-4-enoic acid In acetonitrile for 10h; Reflux; Overall yield = 90 percent; Overall yield = 1.00 g; | General Procedure for arylsulfenylation of unsaturated acids with PhSOCH3 and (COCl)2 in CH3CN. General procedure: To a solution of ArSOCH3 (15 mmol, 3 equivalents) in acetonitrile cooled at 0 °C was addeddropwise a solution of oxalyl chloride (3.75 mmol, 0.75 equivalents) in acetonitrile (10 mL). Themixture was stirred for 10 min at 0 °C. It was then allowed to warm to room temperature and heatedto reflux. Then an unsaturated acid (1a-w) (5 mmol, 1 equivalent) was added and the reactionmixture continued to reflux for 10 h. After cooling to room temperature, the reaction mixture wasthen concentrated on a rotary evaporator and the residue redissolved in CH2Cl2 (100 mL). Theresulting solution was washed with saturated NaHCO3 and brine. The organic phase was dried oversodium sulfate, filtered, concentrated, and the residue purified by flash chromatography on silicagel column to give the arylsulfenylation lactones. (2a-z). The products 2a-w were obtained usingPhSOCH3 and 2x-z obtained using methyl p-methylphenyl sulfoxide, methyl p-fluorophenylsulfoxide, and methyl p-chlorophenyl sulfoxide respectively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Stage #1: racemic methyl phenyl sulfoxide With oxalyl dichloride In acetonitrile at 0℃; Reflux; Stage #2: pent-4-enoic acid In acetonitrile for 10h; Reflux; | General Procedure for arylsulfenylation of unsaturated acids with PhSOCH3 and (COCl)2 in CH3CN. General procedure: To a solution of ArSOCH3 (15 mmol, 3 equivalents) in acetonitrile cooled at 0 °C was addeddropwise a solution of oxalyl chloride (3.75 mmol, 0.75 equivalents) in acetonitrile (10 mL). Themixture was stirred for 10 min at 0 °C. It was then allowed to warm to room temperature and heatedto reflux. Then an unsaturated acid (1a-w) (5 mmol, 1 equivalent) was added and the reactionmixture continued to reflux for 10 h. After cooling to room temperature, the reaction mixture wasthen concentrated on a rotary evaporator and the residue redissolved in CH2Cl2 (100 mL). Theresulting solution was washed with saturated NaHCO3 and brine. The organic phase was dried oversodium sulfate, filtered, concentrated, and the residue purified by flash chromatography on silicagel column to give the arylsulfenylation lactones. (2a-z). The products 2a-w were obtained usingPhSOCH3 and 2x-z obtained using methyl p-methylphenyl sulfoxide, methyl p-fluorophenylsulfoxide, and methyl p-chlorophenyl sulfoxide respectively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: racemic methyl phenyl sulfoxide With oxalyl dichloride In acetonitrile at 0℃; Reflux; Stage #2: (E)-hex-4-en-1-ol With 10-camphorsufonic acid In acetonitrile for 8h; Reflux; Overall yield = 48 percent; Overall yield = 0.50 g; | General Procedure for phenylsulfenylation of unsaturated alcohols with PhSOCH3 and(COCl)2 in CH3CN General procedure: To a solution of PhSOCH3 (15 mmol, 3 equivalents) in acetonitrile cooled at 0 °C was addeddropwise a solution of oxalyl chloride (3.75 mmol, 0.75 equivalents) in acetonitrile (10 mL). Themixture was stirred for 10 min at 0 °C. It was then allowed to warm to room temperature and heatedto reflux. Then an unsaturated alcohol (3a-e) (5 mmol, 1 equivalent) and (±)-CSA (0.5 mmol, 0.1equivalents) were added and the reaction mixture continued to reflux for 8 h. After cooling to roomtemperature, the reaction mixture was then concentrated on a rotary evaporator and the residueredissolved in CH2Cl2 (100 mL). The resulting solution was washed with saturated NaHCO3 and brine. The organic phase was dried over sodium sulfate, filtered, concentrated, and the residuepurified by flash chromatography on silica gel column to give the phenylsulfenylated cyclizationproducts (4a-e). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | Stage #1: racemic methyl phenyl sulfoxide With oxalyl dichloride In acetonitrile at 0℃; Reflux; Stage #2: (4Z)-dec-4-en-1-ol With 10-camphorsufonic acid In acetonitrile for 8h; Reflux; | General Procedure for phenylsulfenylation of unsaturated alcohols with PhSOCH3 and(COCl)2 in CH3CN General procedure: To a solution of PhSOCH3 (15 mmol, 3 equivalents) in acetonitrile cooled at 0 °C was addeddropwise a solution of oxalyl chloride (3.75 mmol, 0.75 equivalents) in acetonitrile (10 mL). Themixture was stirred for 10 min at 0 °C. It was then allowed to warm to room temperature and heatedto reflux. Then an unsaturated alcohol (3a-e) (5 mmol, 1 equivalent) and (±)-CSA (0.5 mmol, 0.1equivalents) were added and the reaction mixture continued to reflux for 8 h. After cooling to roomtemperature, the reaction mixture was then concentrated on a rotary evaporator and the residueredissolved in CH2Cl2 (100 mL). The resulting solution was washed with saturated NaHCO3 and brine. The organic phase was dried over sodium sulfate, filtered, concentrated, and the residuepurified by flash chromatography on silica gel column to give the phenylsulfenylated cyclizationproducts (4a-e). |
63% | Stage #1: racemic methyl phenyl sulfoxide With oxalyl dichloride In acetonitrile at 0℃; for 0.166667h; Stage #2: (4Z)-dec-4-en-1-ol With DL-10-camphorsulphonic acid In acetonitrile at 100℃; for 8h; | 2 (2) Preparation of cis-2-pentyl-3-(phenylthio)tetrahydro-2H-pyran Add 10 mL of anhydrous acetonitrile and methyl phenyl sulfoxide (15 mmol, 1.8 mL) to the three-necked flask, until the temperature of the system drops below 0 °C, slowly add oxalyl chloride (3.75 mmol, 0.33 mL through a 25 mL constant pressure dropping funnel) ) solution in anhydrous acetonitrile (10 mL), after the dropwise addition, stirred at 0 °C for 10 min. Then it was moved to an oil bath, heated to 100°C, cis-4-decen-1-ol (5mmol, 0.87g) and 0.12g (±)-camphorsulfonic acid (0.5mmol) were added in sequence, and the reflux was continued for 8h . TLC tracking, after the enol reaction was completed, the acetonitrile was removed by rotary evaporation, dichloromethane was added, transferred to a separatory funnel, washed twice with saturated sodium bicarbonate solution and saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered ,Rotary evaporation. The obtained crude product was separated by column chromatography (200-300 mesh silica gel; petroleum ether:ethyl acetate=250:1),Obtained cis-2-pentyl-3-(phenylthio)tetrahydro-2H-pyran 0.83g, the phenylthio cyclic etherification product of cis-4-decen-1-ol, with a yield of 63% . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | Stage #1: racemic methyl phenyl sulfoxide With oxalyl dichloride In acetonitrile at 0℃; Reflux; Stage #2: cyclohex-3-enylmethanol With 10-camphorsufonic acid In acetonitrile for 8h; Reflux; | General Procedure for phenylsulfenylation of unsaturated alcohols with PhSOCH3 and(COCl)2 in CH3CN General procedure: To a solution of PhSOCH3 (15 mmol, 3 equivalents) in acetonitrile cooled at 0 °C was addeddropwise a solution of oxalyl chloride (3.75 mmol, 0.75 equivalents) in acetonitrile (10 mL). Themixture was stirred for 10 min at 0 °C. It was then allowed to warm to room temperature and heatedto reflux. Then an unsaturated alcohol (3a-e) (5 mmol, 1 equivalent) and (±)-CSA (0.5 mmol, 0.1equivalents) were added and the reaction mixture continued to reflux for 8 h. After cooling to roomtemperature, the reaction mixture was then concentrated on a rotary evaporator and the residueredissolved in CH2Cl2 (100 mL). The resulting solution was washed with saturated NaHCO3 and brine. The organic phase was dried over sodium sulfate, filtered, concentrated, and the residuepurified by flash chromatography on silica gel column to give the phenylsulfenylated cyclizationproducts (4a-e). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | General procedure: To a solution of ArSOCH3 (15 mmol, 3 equivalents) in acetonitrile cooled at 0 C was addeddropwise a solution of oxalyl chloride (3.75 mmol, 0.75 equivalents) in acetonitrile (10 mL). Themixture was stirred for 10 min at 0 C. It was then allowed to warm to room temperature and heatedto reflux. Then an unsaturated acid (1a-w) (5 mmol, 1 equivalent) was added and the reactionmixture continued to reflux for 10 h. After cooling to room temperature, the reaction mixture wasthen concentrated on a rotary evaporator and the residue redissolved in CH2Cl2 (100 mL). Theresulting solution was washed with saturated NaHCO3 and brine. The organic phase was dried oversodium sulfate, filtered, concentrated, and the residue purified by flash chromatography on silicagel column to give the arylsulfenylation lactones. (2a-z). The products 2a-w were obtained usingPhSOCH3 and 2x-z obtained using methyl p-methylphenyl sulfoxide, methyl p-fluorophenylsulfoxide, and methyl p-chlorophenyl sulfoxide respectively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | Stage #1: racemic methyl phenyl sulfoxide With oxalyl dichloride In acetonitrile at 0℃; Reflux; Stage #2: 3-pentenoic acid In acetonitrile for 10h; Reflux; | General Procedure for arylsulfenylation of unsaturated acids with PhSOCH3 and (COCl)2 in CH3CN. General procedure: To a solution of ArSOCH3 (15 mmol, 3 equivalents) in acetonitrile cooled at 0 °C was addeddropwise a solution of oxalyl chloride (3.75 mmol, 0.75 equivalents) in acetonitrile (10 mL). Themixture was stirred for 10 min at 0 °C. It was then allowed to warm to room temperature and heatedto reflux. Then an unsaturated acid (1a-w) (5 mmol, 1 equivalent) was added and the reactionmixture continued to reflux for 10 h. After cooling to room temperature, the reaction mixture wasthen concentrated on a rotary evaporator and the residue redissolved in CH2Cl2 (100 mL). Theresulting solution was washed with saturated NaHCO3 and brine. The organic phase was dried oversodium sulfate, filtered, concentrated, and the residue purified by flash chromatography on silicagel column to give the arylsulfenylation lactones. (2a-z). The products 2a-w were obtained usingPhSOCH3 and 2x-z obtained using methyl p-methylphenyl sulfoxide, methyl p-fluorophenylsulfoxide, and methyl p-chlorophenyl sulfoxide respectively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | Stage #1: racemic methyl phenyl sulfoxide With oxalyl dichloride In acetonitrile at 0℃; Reflux; Stage #2: dec-3-enoic acid In acetonitrile for 10h; Reflux; | General Procedure for arylsulfenylation of unsaturated acids with PhSOCH3 and (COCl)2 in CH3CN. General procedure: To a solution of ArSOCH3 (15 mmol, 3 equivalents) in acetonitrile cooled at 0 °C was addeddropwise a solution of oxalyl chloride (3.75 mmol, 0.75 equivalents) in acetonitrile (10 mL). Themixture was stirred for 10 min at 0 °C. It was then allowed to warm to room temperature and heatedto reflux. Then an unsaturated acid (1a-w) (5 mmol, 1 equivalent) was added and the reactionmixture continued to reflux for 10 h. After cooling to room temperature, the reaction mixture wasthen concentrated on a rotary evaporator and the residue redissolved in CH2Cl2 (100 mL). Theresulting solution was washed with saturated NaHCO3 and brine. The organic phase was dried oversodium sulfate, filtered, concentrated, and the residue purified by flash chromatography on silicagel column to give the arylsulfenylation lactones. (2a-z). The products 2a-w were obtained usingPhSOCH3 and 2x-z obtained using methyl p-methylphenyl sulfoxide, methyl p-fluorophenylsulfoxide, and methyl p-chlorophenyl sulfoxide respectively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | Stage #1: racemic methyl phenyl sulfoxide With oxalyl dichloride In acetonitrile at 0℃; Reflux; Stage #2: 1,2,5,6-tetrahydrobenzoic acid In acetonitrile for 10h; Reflux; | General Procedure for arylsulfenylation of unsaturated acids with PhSOCH3 and (COCl)2 in CH3CN. General procedure: To a solution of ArSOCH3 (15 mmol, 3 equivalents) in acetonitrile cooled at 0 °C was addeddropwise a solution of oxalyl chloride (3.75 mmol, 0.75 equivalents) in acetonitrile (10 mL). Themixture was stirred for 10 min at 0 °C. It was then allowed to warm to room temperature and heatedto reflux. Then an unsaturated acid (1a-w) (5 mmol, 1 equivalent) was added and the reactionmixture continued to reflux for 10 h. After cooling to room temperature, the reaction mixture wasthen concentrated on a rotary evaporator and the residue redissolved in CH2Cl2 (100 mL). Theresulting solution was washed with saturated NaHCO3 and brine. The organic phase was dried oversodium sulfate, filtered, concentrated, and the residue purified by flash chromatography on silicagel column to give the arylsulfenylation lactones. (2a-z). The products 2a-w were obtained usingPhSOCH3 and 2x-z obtained using methyl p-methylphenyl sulfoxide, methyl p-fluorophenylsulfoxide, and methyl p-chlorophenyl sulfoxide respectively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | Stage #1: racemic methyl phenyl sulfoxide With oxalyl dichloride In acetonitrile at 0℃; Reflux; Stage #2: (cyclopent-2-eneyl)acetic acid In acetonitrile for 10h; Reflux; | General Procedure for arylsulfenylation of unsaturated acids with PhSOCH3 and (COCl)2 in CH3CN. General procedure: To a solution of ArSOCH3 (15 mmol, 3 equivalents) in acetonitrile cooled at 0 °C was addeddropwise a solution of oxalyl chloride (3.75 mmol, 0.75 equivalents) in acetonitrile (10 mL). Themixture was stirred for 10 min at 0 °C. It was then allowed to warm to room temperature and heatedto reflux. Then an unsaturated acid (1a-w) (5 mmol, 1 equivalent) was added and the reactionmixture continued to reflux for 10 h. After cooling to room temperature, the reaction mixture wasthen concentrated on a rotary evaporator and the residue redissolved in CH2Cl2 (100 mL). Theresulting solution was washed with saturated NaHCO3 and brine. The organic phase was dried oversodium sulfate, filtered, concentrated, and the residue purified by flash chromatography on silicagel column to give the arylsulfenylation lactones. (2a-z). The products 2a-w were obtained usingPhSOCH3 and 2x-z obtained using methyl p-methylphenyl sulfoxide, methyl p-fluorophenylsulfoxide, and methyl p-chlorophenyl sulfoxide respectively. |
Tags: 1193-82-4 synthesis path| 1193-82-4 SDS| 1193-82-4 COA| 1193-82-4 purity| 1193-82-4 application| 1193-82-4 NMR| 1193-82-4 COA| 1193-82-4 structure
[ 22821-85-8 ]
1,3-Bis(methylsulfonyl)benzene
Similarity: 0.83
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