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CAS No. : | 104-95-0 | MDL No. : | MFCD00000102 |
Formula : | C7H7BrS | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | YEUYZNNBXLMFCW-UHFFFAOYSA-N |
M.W : | 203.10 | Pubchem ID : | 66037 |
Synonyms : |
|
Num. heavy atoms : | 9 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.14 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 0.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 45.86 |
TPSA : | 25.3 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | Yes |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -5.32 cm/s |
Log Po/w (iLOGP) : | 2.36 |
Log Po/w (XLOGP3) : | 3.12 |
Log Po/w (WLOGP) : | 3.17 |
Log Po/w (MLOGP) : | 3.64 |
Log Po/w (SILICOS-IT) : | 3.08 |
Consensus Log Po/w : | 3.07 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.49 |
Solubility : | 0.0654 mg/ml ; 0.000322 mol/l |
Class : | Soluble |
Log S (Ali) : | -3.32 |
Solubility : | 0.0972 mg/ml ; 0.000478 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -3.75 |
Solubility : | 0.036 mg/ml ; 0.000177 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.64 |
Signal Word: | Danger | Class: | 9 |
Precautionary Statements: | P261-P264-P271-P280-P302+P352-P304+P340+P312-P305+P351+P338+P310-P332+P313-P403+P233-P405-P501 | UN#: | 3335 |
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 |
---|---|---|
10% | Stage #1: With n-butyllithium In tetrahydrofuran at -78 - 20℃; for 0.333333 h; Stage #2: With Triisopropyl borate In tetrahydrofuran at -78 - 20℃; for 3 h; |
Example 62; Preparation of 5-(4-fluoro-phenyl)-1-methyl-7-(4-methylsulfanyl-phenyl)-3-propyl-1H-pyrazolo[4,3-d]pyrimidine (E 62); Step 1: Preparation of 4-methylsulfanyl phenyl boronic acid To a cold (-78° C.) and stirring solution of 4-bromothioanisole (10) (3 grams, 14.8 mmol) in THF (15 mL) was added n-BuLi (10 mL) slowly under nitrogen atmosphere. The mixture was the allowed to reach the room temperature and stirring continued for 20 minutes. The mixture was then cooled to -78° C. A solution of triisopropyl borate (10 mL, 17.7 mmol) in THF (10 mL) was added to it slowly. The mixture was stirred for 1 hour at -78° C. and then 2 hours at room temperature. The mixture was acidified with cold 5percent HCl, diluted with water (25 mL) and extracted with ethyl acetate. The organic layers were collected, combined, washed with brine solution (20 mL) followed by water (20 mL), dried over anhydrous Na2SO4 and concentrated. The residue thus obtained was purified by column chromatography using EtOAc-Hexane to afford the required aryl boronoc acid (11) (170 mg,). Yield: 10percent; 1H NMR (200 MHz, CDCl3): δ 8.10 (d, J=7.9 Hz, 2H), 7.33 (d, J=7.9 Hz, 2H), 2.55 (s, 3H, SCH3), 1.56 (bs, D2O exchangeable, OH), 1.25 (s, exchangeable, OH). IR: vmax (KBr, cm-1): 3406, 1594. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With N-Bromosuccinimide; methyl 2-n-pentyl-1H-indole-3-carboxylate In n-heptane at 23℃; for 48h; Darkness; Green chemistry; regioselective reaction; | |
87.4% | With bromine In pentane for 0.5h; Ambient temperature; | |
84.7% | With bromine In pentane for 0.5h; |
69% | With copper(II) choride dihydrate; ethanol; carbon dioxide; oxygen; lithium bromide at 20 - 100℃; for 12h; Autoclave; regioselective reaction; | |
With N-Bromosuccinimide | ||
With bromine In acetic acid at 100℃; | ||
41 %Chromat. | With carbon dioxide; oxygen; lithium bromide; copper(ll) bromide In water at 100℃; for 10h; Autoclave; Green chemistry; regioselective reaction; | oxybromination of aromatic ethers General procedure: A mixture of substrate (1 mmol), CuBr2 (22.4 mg, 10 mol%), LiBr (130.3 mg, 1.5 equiv.), and 0.05 mL of water was placed in a 50 mL stainless steel autoclave equipped with an inner glass tube in room temperature. CO2 (4 MPa) and O2 (1 MPa) were subsequently introduced into the autoclave and the system was heated under the predetermined reaction temperature for 15 min to reach the equilibration. Then the final pressure was adjusted to the desired pressure by introducing the appropriate amount of CO2. The mixture was stirred continuously for the desired reaction time. After cooling, products were diluted with acetone and analyzed by gas chromatograph (Shimadzu GC-2014) equipped with a capillary column (RTX-17 30 m × 25 μm and RTX-wax 30 m × 25 μm) using a flame ionization detector by comparing the retention times of authentic samples. The residue was purified by column chromatography on silica gel (200-300 mesh, eluting with petroleum ether/ethyl acetate from petroleum ether to 50:1) to afford the desired product. The isolated products were further identified with NMR spectra (Bruker 400 MHz) and GC-MS or GCD, which are consistent with those reported in the literature. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With perpropionic acid In ethanol; dichloromethane at 20℃; for 24h; | |
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 24h; Irradiation; | |
99% | With lithium hydroxide monohydrate; bromine; mesoporous silica In dichloromethane at 20℃; for 0.166667h; |
99% | With iron(III) chloride; orthoperiodic acid In acetonitrile at 20℃; for 0.025h; | |
99% | With iodosylbenzene; 3,5-disubstituted Cr(salen) In dichloromethane at 20℃; for 2.5h; | |
99% | With dihydrogen peroxide In acetonitrile at 31.85℃; for 1h; | |
99% | With sodium hydrogen sulphate monohydrate; [bis(acetoxy)iodo]benzene for 0.0166667h; Neat (no solvent); | |
99% | With dihydrogen peroxide; glacial acetic acid at 0 - 20℃; | |
99% | With phthaloyl peroxide In dichloromethane at 25℃; for 8h; Schlenk technique; chemoselective reaction; | |
99% | With palladium; dihydrogen peroxide In methanol at 60℃; for 16h; Green chemistry; chemoselective reaction; | |
99% | With 1,3-dimethylhexahydro-2,4,5,6-pyrimidinetetraone; dihydrogen peroxide; magnesium(II) sulfate In dichloromethane at 25℃; for 0.5h; | |
99% | With dihydrogen peroxide In neat (no solvent) at 20℃; for 1.33333h; chemoselective reaction; | |
98% | With cerium(III) sulphate; barium bromate In lithium hydroxide monohydrate; acetonitrile at 20℃; for 0.75h; | |
98% | With anhydrous zinc chloride; 2-isopropyl-3-(pyridin-2-yl)oxaziridine In chloroform for 2h; | |
98% | With 1-iodyl-2-isopropoxybenzene In acetonitrile for 8h; Heating; | |
98% | With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 0℃; for 16h; | |
97% | With dihydrogen peroxide In lithium hydroxide monohydrate; acetonitrile at 24.84℃; for 2.5h; | |
97% | With 1,3-dihydroxy-1H-1λ3-benzo[d][1,2]iodoxol-1-yl trifluoromethanesulfonate In acetonitrile at 20℃; for 0.166667h; Inert atmosphere; | General procedure for oxidation of sulfides to sulfoxides using IBA-OTf 2 General procedure: Sulfide 3 (0.125 mmol) was added to a solution of 2 (62 mg, 0.15 mmol) in acetonitrile (1 mL). The reaction was stirred at room temperature for 10 min to 1 h (reaction completion was controlled by TLC). After completion of the reaction, 5% aqueous Na2S2O3 (5 mL) and saturated NaHCO3 (5 mL) were added, and the mixture was extracted with dichloromethane. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification using short chromatographic column (hexane-ethyl acetate = 3 : 1) afforded analytically pure sulfoxide 4. |
97% | With dihydrogen peroxide In lithium hydroxide monohydrate at 20℃; for 1.33333h; Green chemistry; | 2.5. General procedure for catalytic oxidation of sulfides to sulfoxides General procedure: In a typical procedure, the sulfide oxidation reaction was carried out by placing organic substrate (5 mmol), catalyst containing 0.005 mmol of Ti [PATi (1.40 mg) or PMATi (1.88 mg)], 30% H2O2 (2.26 mL, 20 mmol) in 5 mL of water in a round bottom flask. The molar ratio of Ti: substrate was maintained at 1:1000 and substrate: H2O2 at 1:4. Reaction was conducted at ambient temperature under magnetic stirring. The progress of the reaction was monitored by thin layer chromatography (TLC) and GC. After completion of the reaction, the oxidized product along with unreacted organic substrate were extracted with diethyl ether, dried over anhydrous sodium sulfate and distilled under reduced pressure to remove excess diethyl ether. The product was then purified by column chromatography on silica gel with ethyl acetate-hexane (1: 9 v/v) as the eluent. The product obtained was characterized by IR, 1H NMR, 13C NMR spectroscopy and melting point determination (for solid products) [Text S1 (Supporting Information)]. |
97% | With 1,6,8-trihydroxy-3-methyl-9,10-anthraquinone In methanol at 20℃; for 6h; Irradiation; | |
97% | With oxygen In methanol; lithium hydroxide monohydrate at 20℃; for 13h; Irradiation; Green chemistry; | |
96% | With [MoO(O2)2(O-pyridine)(H2O)] coated on SiO2 In methanol; acetonitrile at 20℃; for 11h; | |
96% | With NBS; β‐cyclodextrin In lithium hydroxide monohydrate; propan-2-one at 20℃; for 2h; | |
96% | With ferric(III) chloride; orthoperiodic acid In acetonitrile at 25℃; Inert atmosphere; | |
96% | With Ni(N,N′‑dimethyl‑N,N′‑bis(pyridine‑2‑ylmethyl)‑1,2‑diaminoethane)Cl2; dihydrogen peroxide In acetonitrile at 20℃; for 2h; | 6 Add 1.0mmol sulfide 5a, 2.5mmol 30wt% H2O2, 0.008mmol nickel catalyst, and 2mL solvent acetonitrile to the reaction tube, and react for 2h at room temperature. After the reaction product mixture is concentrated and separated by column chromatography, the corresponding The isolated yield is 96%. |
96% | With methanol; oxygen at 20℃; for 12h; Irradiation; | |
95% | With ortho-nitrophenylsulfinyl chloride In acetonitrile at -25℃; for 5h; | |
95% | With glacial acetic acid In ethyl acetate at 0℃; for 3h; | |
95% | With aluminum(III) oxide; sodium hypochlorite In propan-2-one at 20℃; for 0.416667h; | |
95% | With NBS; lithium hydroxide monohydrate; mesoporous silica In dichloromethane at 20℃; for 0.75h; | |
95% | With dihydrogen peroxide In tetrahydrofuran at 20℃; for 0.0833333h; | |
95% | With NaBrO3; CAN; mesoporous silica In dichloromethane at 20℃; for 0.25h; | |
95.5% | Stage #1: 1-bromo-4-(methylthio)benzene With ferric(III) chloride In acetonitrile at 20℃; for 0.166667h; Stage #2: With orthoperiodic acid In acetonitrile at 0℃; for 1h; | a 1-bromo-4-( methylsulfinyl)benzene To a solution of (3-bromophenyl)(methyl)sulfane (100.0 g, 0.492 mol) in CH3CN (500 mL) was added FeCI3 (2.4 g, 14.8 mmol) with stirring. After the addition, the mixture was stirred at room temperature for 10 mm and then cooled to 0 °C. H5105 (124.2 g, 0.545 mol) was added in portions and the mixture was stirred at 0 °C for 1 h. TLC (PE : EA = 5 : 1, Rf = 0.2) showed the most of starting material was consumed. The reaction mixture was quenched by the addition of saturatedaqueous NH4CI (1.0 L) and extracted with EA (300 mL x 4). The organic layers were washed with brine (300 mL), dried over Na2SO4 and concentrated. The residue was purified by chromatography on silica gel (PE/EA = 20: 1 5: 1) to give 1-bromo-4-(methylsulfinyl)benzene (103.0 g, 95.5% of theory) as a white solid. |
95% | With dihydrogen peroxide In ethyl acetate for 0.833333h; Heating; | |
95% | With dihydrogen peroxide In lithium hydroxide monohydrate at 20℃; for 0.833333h; Green chemistry; chemoselective reaction; | |
95% | With pyrene 1, 6-quinone; oxygen; isopropanol at 20℃; for 24h; Irradiation; Green chemistry; | |
95% | With lithium hydroxide monohydrate; tetra-n-butylammonium dihydrogen phosphate In acetonitrile at 20℃; for 2h; Electrochemical reaction; chemoselective reaction; | |
95% | With air; phenothiazine on covalent triazine frameworks In [D3]acetonitrile at 20℃; for 2h; Irradiation; | |
94% | With dihydrogen peroxide; 8-chloro-1,10-ethyleneisoalloxazinium chloride In methanol at 25℃; for 12h; chemoselective reaction; | |
94% | With urea hydrogen peroxide addition compound In neat (no solvent, solid phase) at 20℃; for 0.583333h; Green chemistry; | 2.3 General procedure for the oxidation reactions catalyzed by UHP/SSA General procedure: The solid reaction mixture containing the sulfide (1mmol), UHP (2mmol) and SSA (0.1g) were thoroughly mixed and the resulting mixture was stirred magnetically. The progress of the reaction was followed by TLC (eluent: n-hexane/ethyl acetate: 2:1). After completion of the reaction, CHCl3 (20mL) was added and the solid catalyst was removed by filtration. The filtrate was washed with water (15mL) and the extract was dried over MgSO4. After evaporation of the solvent, the crude product was purified by chromatography on silica gel (25-30mesh), eluting with ethyl acetate/n-hexane to give pure sulfoxides. |
94% | With anthraquinone-2-carbonyl immobilized onto poly(2-hydroxyethyl methacrylate); air In methanol at 20℃; for 27h; chemoselective reaction; | |
93% | With magnesium monoperoxyphthalate hexahydrate; bentonite In acetonitrile at 29.9℃; for 1h; | |
93% | With 1-methylimidazolium hydrogen sulphate; ammonium cerium (IV) nitrate at 80℃; for 0.166667h; neat (no solvent); | |
93% | With dihydrogen peroxide In methanol; lithium hydroxide monohydrate at 25℃; for 1.5h; | |
93% | With dihydrogen peroxide In neat (no solvent) at 20℃; for 0.416667h; chemoselective reaction; | |
93% | With ferric(III) chloride; urea hydrogen peroxide addition compound In acetonitrile at 20℃; for 2.08333h; Green chemistry; | 2.2 General Procedure: Oxidation Reactions CatalyzedbyUHP/FeCl3 System inCH3CNasSolvent General procedure: In a 25 round-bottomed flask, to a solution a sulfide(1mmol) in CH3CN(10mL), UHP (1.5mmol) and FeCl3(1 mmol) were added successively and the mixture wasstirred magnetically at room temperature. The reaction progresswas followed by TLC (eluent: n-hexane/ethyl acetate:2:1). After completion of the reaction, the solvent wasremoved under vacuum and the residue was quenched byadding water (15mL), extracted with CH2Cl2(3 × 10mL).The combined organic layers were washed with water,dried over MgSO4and the solvent was removed in vacuum.The residue was purified by chromatography on silica gel(25-30 mesh), eluting with ethyl acetate/n-hexane to givepure sulfoxides. |
93% | With pyridine; methanol; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; oxygen; copper(II) sulphate at 65℃; for 10h; Schlenk technique; Green chemistry; chemoselective reaction; | Procedures for the selective aerobic oxidation of sulfides to sulfoxides General procedure: TEMPO (3.1mg, 0.02mmol), Methanol (1mL), CuSO4 (4.0mg, 0.03mmol), pyridine (8.1µL, 0.1mmol), and sulfides (0.5mmol), were added into the Schlenk tube (100mL). The reaction mixture was stirred at 65 and under O2 conditions for the given time. After the completion of the reaction, the reaction mixture was cooled to the room temperature, ethyl acetate (10mL) was added. And some solid was precipitated. Then, the mixture was filtered, and the solid was washed with petroleum ether and dried which was used directly in recycle experiments. The filtrate was concentrated under reduced pressure. The crude product was purified by column chromatography (silica 300-400, petroleum ether/ethyl acetate mixture = 5/1 and 2/1) to afford the product. |
93% | With 1,1′-(butane-1,4-diyl)bis(1,4-diazabicyclo[2.2.2]octane-1,4-diium) bis(hydrogen sulfate) dinitrate; potassium bromide In neat (no solvent) at 20℃; for 0.2h; Green chemistry; | 2.5. General procedure for the oxidation of sulfides General procedure: A mixture of an sulfide (1 mmol), [C4(DABCO-H)2]·[HSO4]2[NO3]2(0.5 mmol) and KBr (0.05 mmol) was vigorously grind using a mortarand pestle at roomtemperature. After completion of the reaction (monitoredby TLC), 5 mL water was added to the mortar and the mixturewas filtered to separate the nitrated product. The products were purifiedwith short column chromatography. |
93% | With Fe3O4-rose bengal-layered double hydroxide In lithium hydroxide monohydrate at 20℃; for 48h; Irradiation; | |
93% | With dihydrogen peroxide In neat (no solvent) at 20℃; for 1.66667h; | |
92% | With urea hydrogen peroxide; 1-ethyl-3-methyl-1H-imidazolium tetrafluoroborate at 20℃; for 3h; | |
92% | With iodosylbenzene; VO(4-bromo-2-[(2,6-diisopropylphenylimino)methyl]phenol(-H))2 at 20℃; for 1.58333h; | Typical procedure for sulfoxidation General procedure: VO (BrDPMP)2 (0.1 mmol) and sulfide (1 mmol) were dissolved in CH2Cl2 (3 ml) and the solution was stirred for five minutes. Tothis solution PhIO was added (1.1 mmol) at once. The reaction was monitored by TLC at regular intervals and continued for stipulated reaction time. After removal of the solvent, the residue waspurified by Silica gel flash chromatography to afford sulfoxide. All the sulfoxides thus obtained were identified by comparing NMR data with values reported in the literature [8] and those of the authentic samples. |
92.7% | With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 1h; | 78.1 Step 1: 121-2 To a mixture of 121-1 (2 g, 9.85 mmol) in DCM (50 mL) was added m-CPBA (2.10 g, 10.34 mmol, 85%purity) at 20 . The mixture was stirred for 1 hr at 20 . Then, the solution was washed with saturated aqueous sodium sulfite (10 mL) , saturated aqueous NaHCO3(20 mL × 2) and brine (15 mL) , dried over anhydrous sodium sulfate and concentrated with a rotary evaporator. The crude product was purified by silica gel chromatography (ethyl acetate in petroleum ether, 0 -60%) to obtain 121-2 (2.0 g, 9.13 mmol, 92.70%yield) . MS: m/z = 220 (M+1) . |
91% | With bromine; oxygen; potassium nitrate||KNO3||NO3K In acetonitrile at 20℃; for 3h; chemoselective reaction; | |
90% | With aluminum(III) oxide; sodium hypochlorite; Mn(salen)Cl In dichloromethane at 20℃; for 0.333333h; | |
90% | With Fe2O<(-)4,5 pinene bipyridine>4(H2O)2(ClO4)4; dihydrogen peroxide at -15℃; for 0.166667h; | |
90% | With ferric(III) bromide; iron nitrate (III) In acetonitrile at 25℃; for 1.25h; | |
90% | With NaBrO3; magnesium hydrogen sulfate at 60℃; for 0.5h; | |
90% | With NaBrO3; sulfuric acid; mesoporous silica at 20℃; for 0.45h; | |
90% | With lithium hydroxide monohydrate In acetonitrile at 20℃; for 0.25h; | |
90% | With iodosylbenzene; C75H102Cl3Fe3N6O6 In dichloromethane at 20℃; for 15h; chemoselective reaction; | |
90% | With dihydrogen peroxide; glacial acetic acid at 0 - 20℃; | |
90% | With nickel(II) ferrite; dihydrogen peroxide In acetonitrile at 20℃; for 2.5h; Green chemistry; chemoselective reaction; | |
90% | With dihydrogen peroxide In ethanol at 20℃; for 2h; Green chemistry; | General Experimental Procedure for the Preparation of Sulfoxides General procedure: In a typical reaction, a mixture of CSA (0.07 g equal to 0.34 mmol H+), diphenylsulfide (1 mmol), hydrogen peroxide (aq. 30%, 1.5 mmol), and ethanol (5 mL) was stirredat r.t. for 240 min. The progress of reaction was monitored by TLC method. At the end ofthe reaction, catalyst was removed by filtration and the resulting solution was concentratedunder reduced pressure. Then, residue was purified by column chromatography on silicagel (n-hexane-ethyl acetate 1 : 5) to afford 0.192 g (93%) of diphenyl sulfoxide as a whitesolid. The resulting products were determined by their 1H-NMR spectra and compared withthe authentic samples. |
90% | With dihydrogen peroxide at 20℃; for 0.0833333h; Green chemistry; chemoselective reaction; | |
90% | With air; eosin Y supported on Amberlite IRA 900 resin In lithium hydroxide monohydrate; acetonitrile at 20℃; for 6h; Irradiation; | |
89% | With lithium hydroxide monohydrate; mesoporous silica; pyridinium hydrobromide perbromide In dichloromethane for 2.16667h; | |
89% | With tert.-butylhydroperoxide; Aminoiminomethanesulfinic acid In dodecane; dichloromethane at 20℃; for 5h; chemoselective reaction; | General experimental procedure for TUD catalyzed oxidation of sulfides with TBHP: To the stirred mixture of sulfide (1 mmol), anhydrous TBHP in dodecane (1.5 mmol) in dichloromethane (3 ml) was added catalyst TUD (2 mol %). The resulting mixture was stirred at room temperature for the time reported in the Table 2. Progress of the reaction was monitored by TLC. After completion, the reaction mixture was diluted with dichloromethane and washed with water (3 × 15 ml). The organic layer was separated, dried over anhydrous MgSO4 and concentrated under reduced pressure. The crude product was purified with column chromatography (SiO2) using ethyl acetate/hexane (4:6) as eluent. The selectivity and conversion were determined by high resolution GC-MS analysis; however the identity of the products was confirmed by comparing their physical and spectral data with the known compounds. |
89% | With C20H32NO4V; dihydrogen peroxide In lithium hydroxide monohydrate at 20℃; for 144h; | |
88% | With dihydrogen peroxide In ethanol at 25 - 35℃; for 1.25h; Irradiation; | 2.3. General procedure for the oxidation reaction of sulfides and alcoholsin the presence of PW4Mo8/g-C3N4 as photocatalyst General procedure: A mixture of sulfide or alcohol (1 mmol), 0.5 mL of H2O2 33%, 10 mLof ethanol as solvent, and 0.005 g of PW4Mo8/g-C3N4 as photocatalystwas added. The reaction mixture was then stirred under visible lightirradiation for an appropriate time (Table 2, 3) until the completion ofthe reaction was achieved as monitored by TLC. After the photocatalyticreaction, the suspension was centrifuged at 5000 rpm for 10 min and thesupernatant was analyzed by gas chromatography (GCYonglin 6100; BPScheme 5; 30 m × 0.25 × mm × 0.25 μm). |
87% | With tert.-butylhydroperoxide; bis[rhodium(α, α, α’,α’-tetramethyl-1,3-benzenedipropionic acid)] In dichloromethane at 20℃; for 34h; | |
87% | With oxygen In lithium hydroxide monohydrate; acetonitrile at 23 - 27℃; for 0.75h; Irradiation; Green chemistry; chemoselective reaction; | |
87% | Stage #1: 1-bromo-4-(methylthio)benzene With Aluminum Chloride In methanol; dichloromethane at 20℃; for 0.0166667h; Stage #2: With [bis(acetoxy)iodo]benzene In methanol; dichloromethane at 20℃; for 12h; | 2. General Procedure for the Selective Oxidation of Sulfides General procedure: To a 25 mL glass tube, sulfide (1 mmol), MeOH (0.5ml), CH2Cl2(4.5ml), and AlCl3(0.5 mmol) were added and the mixture was stirred at room temperature for 1min.Then, PhI(OAc)2 (1.0 equiv) was added and the solution was stirred at roomtemperature. After the disappearance of the sulfide material (checked by TLC), thesolvent was removed under reduced pressure. The crude was purified by columnchromatography on silica gel (200-300 mesh) with ethyl acetate/petroleum ether. |
87% | With oxygen; 2,9-bis(2,6-diisopropylphenyl)anthra[2,1,9-def:6,5,10-d'e'f']diisoquinoline-1,3,8,10(2H,9H)-tetraone In methanol at 20℃; Irradiation; | 5 Example 5 Preparation of p-bromophenyl methyl sulfoxide In a dry Shrek reaction tube,Add p-bromophenyl methyl sulfide (0.25 mmol) sulfide to methanol (2.0 mL)PDI (0.5 mol%), PDI is a compound of formula A.Next, fill a balloon with oxygen and fix it on top of the Shrek reaction tube.The reaction was carried out at room temperature with a 15 W white CFL irradiation under a normal pressure of oxygen.After the reaction was completed, brine was added to the reaction.The aqueous phase was re-extracted with ethyl acetate.The synthesized organic extract was dried over Na 2 SO 4 and concentrated in vacuo.The residue obtained was separated by silica gel column chromatography ( petroleum ether: ethyl acetate = 10:1).Purification gave a white viscous solid (yield: 87%; selectivity: 100%). |
87% | With cercosporin; oxygen In methanol at 20℃; Schlenk technique; Irradiation; Green chemistry; chemoselective reaction; | |
87% | With diethylene glycol dibutyl ether; oxygen; sodium trifluoro-methanesulfinate at 20℃; for 12h; Irradiation; | |
86% | With mesoporous silica; iron nitrate (III) In hexane at 60℃; for 2.5h; | |
86% | With tert.-butylhydroperoxide; lanthanum(III) oxide In lithium hydroxide monohydrate; ethyl acetate at 90℃; for 5.5h; Green chemistry; | |
86% | With 3,3-dimethyl-2,4-pentanedione; dihydrogen peroxide In chloroform; lithium hydroxide monohydrate at 25℃; for 7h; | 6. General procedure for catalytic sulfoxidation General procedure: H2O2(aq) (50%, 285 mL, 5.00 mmol, 5 equiv) was added to a solutionof sulfide (1.00 mmol, 1 equiv), 3,3-dimethylpentane-2,4-dione 7 (26 mL, 0.20 mmol, 0.2 equiv) and SSA (100 mg) in CHCl3(2.5 mL). The resulting biphasic solutionwas stirred at 25 C for thetime indicated and monitored by TLC or HPLC. The reaction wasfiltered into saturated Na2S2O5(aq) (2 mL) and H2O (10 mL) and thesolid washed with EtOAc (3 5 mL). The aqueous layer was furtherextracted with EtOAc (2 15 mL). The combined organics werewashed with brine (10 mL), dried with MgSO4 and filtered. Thesolvent was removed in vacuo and the crude material was thenpurified by silica gel chromatography (petrol:EtOAc) to obtain thetarget products. All oxidations were run in duplicate and presentedresults are an average of 2 runs. |
86% | With lithium hydroxide monohydrate In acetonitrile at 20℃; Electrochemical reaction; Flow reactor; | |
86% | With oxygen In methanol at 20℃; for 12h; Irradiation; | |
85% | With dihydrogen peroxide In methanol at 25℃; for 3h; | |
85% | With dihydrogen peroxide In 1,2-dichloro-ethane for 0.333333h; Reflux; | |
85% | With oxygen; 2,9-bis(2,6-diisopropylphenyl)anthra[2,1,9-def:6,5,10-d'e'f']diisoquinoline-1,3,8,10(2H,9H)-tetraone In methanol at 20℃; for 14h; Schlenk technique; Irradiation; Green chemistry; | |
85% | With dihydrogen peroxide In ethanol at 25 - 35℃; for 1.66667h; Irradiation; | 2.5 General procedure for the oxidation of sulfides to sulfoxides General procedure: A mixture of sulfide (1mmol), H2O2 33% (0.5mL), ethanol as solvent (10mL) and Mo6W6EDMG (0.005g) as catalyst was added to a Pyrex flask. The mixture was stirred under visible light irradiation (a 400W lamp, high-pressure mercury-vapor lamp with UV filter (Oriel, 51472) was used as a visible light irradiation source) for the required time to complete the reaction. When the reaction was completed, the catalyst separated. The product was extracted with CH2Cl2, washed with water (6mL) and evaporated the solvent to give the corresponding pure sulfoxide. |
84% | With cyclo(-L-Pro-L-Pro-) hydroperoxide In methanol at 20℃; for 72h; | |
84% | With dihydrogen peroxide; scandium trifluoromethanesulphonate In ethanol; dichloromethane; lithium hydroxide monohydrate at 20℃; for 8h; | |
84% | With tetra-n-butylammonium tetrafluoroborate; lithium hydroxide monohydrate In N,N-dimethyl-formamide at 25℃; for 10h; Electrochemical reaction; | |
84% | With tetra-n-butylammonium tetrafluoroborate; oxygen In dichloromethane at 20℃; for 2h; Electrochemical reaction; Green chemistry; | |
83% | With sodium bromite; "wet" H(1+)-exchanged zeolite F-9 In dichloromethane for 1h; Ambient temperature; | |
83% | With 1,3-dimethyl-5-ethyl-5,10-dihydro-7-carboxyalloxazine; 1,3-dimethyl-5-ethyl-5,10-dihydro-8-carboxyalloxazine; dihydrogen peroxide In methanol; lithium hydroxide monohydrate at 20℃; for 5h; | |
83% | With hydrogenchloride; tetra-n-butylammonium perchlorate; oxygen In lithium hydroxide monohydrate; acetonitrile for 0.333333h; Electrochemical reaction; Flow reactor; Green chemistry; | |
83% | With oxygen; lithium perchlorate In N,N-dimethyl-formamide at 25℃; for 5h; Electrochemical reaction; | 17 Example 1 General procedure: In a 10mL reaction flask without diaphragm, add diphenyl sulfide 2a (56mg, 0.3mmol), electrolyte lithium perchlorate (5mg, 0.05mmol) in sequenceAnd 4mL solvent N,N-dimethylformamide (DMF).The reaction flask is equipped with graphite rod as anode (length 8mm × width 2mm × height 50mm), nickel plate as cathode (length 8mm × width 2mm × height 50mm), the distance between the electrodes is 5mm, and the lower ends of the anode and cathode are inserted under the liquid surface The depth of the two electrodes (anode and cathode) is 8mm, and the length and height of the two electrodes (anode and cathode) are arranged parallel to each other (the area of the opposite surface of the anode and cathode placed in the reaction solution is 64mm2).A balloon filled with oxygen was connected to the reaction flask, and the reaction was stirred for 3 hours at a constant current of 7 mA and room temperature at 25°C.After the reaction, the mixture was cooled to room temperature and extracted with ethyl acetate (3×10 mL, three times, 10 mL each time). The ethyl acetate layers were combined, dried with anhydrous sodium sulfate, filtered, and volatile was removed under reduced pressure. The components are then separated by silica gel column chromatography (the eluent is petroleum ether (60-90/ethyl acetate, v/v=25:1),The target product 1a (51 mg, yield 84%) was obtained as a white solid. The target product was confirmed by high-resolution mass spectrometry, infrared spectroscopy, and nuclear magnetic resonance spectroscopy. |
83% | With lithium perchlorate trihydrate; lithium hydroxide monohydrate; oxygen In N,N-dimethyl-formamide at 20℃; Electrochemical reaction; chemoselective reaction; | |
82% | With iodosylbenzene In acetonitrile at 45℃; for 1h; | |
82% | With kaoline; sodium bromite In dichloromethane for 0.25h; Ambient temperature; | |
82% | With 2-iodyl-3-propoxypyridine In acetonitrile for 2.5h; Reflux; Inert atmosphere; chemoselective reaction; | |
82% | With cross-linked poly(N-vinylpyrrolidone):H2O2 complex (1:4.5) In acetonitrile at 70℃; for 24h; | |
81% | With isopropyl 2-iodoxybenzoate In acetonitrile Heating; | |
81% | With tert.-butylhydroperoxide In acetonitrile at 80℃; for 24h; | 4 4-bromobenzyl sulfide (20 mmol, 4.04 g) was added sequentially to a 100 mL single-mouth bottle.70% t-butyl hydroperoxide (80 mmol, 10.29 g) and 40 mL acetonitrile were reacted at 80 ° C for 24 h.After the reaction was completed (TLC monitoring), the heating was stopped, and after cooling to room temperature, 100 mL of water was added.It was extracted with dichloromethane (3×100 mL).Column chromatography (developing solvent: petroleum ether: ethyl acetate = 20:1) gave white title product.Yield 81% (3.53 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 0 - 23℃; for 12h; | |
100% | With dihydrogen peroxide In propyl alcohol; lithium hydroxide monohydrate at 25℃; for 5h; | |
100% | With sodium (meta)periodate; ruthenium on carbon In lithium hydroxide monohydrate at 20℃; for 2h; | 6 Add 0.01 g of Ru / C catalyst and 235 mg (1.1 mmol) of sodium periodate to the reaction flask, add 3 mL of water, and then add 203 mg (1 mmol) of 4-bromoanisole I-6 to the reaction with stirring In the flask, react for 2h at room temperature. The reaction of 4-bromoanisole was detected by TLC, and the reaction was stopped. The reaction solution was filtered and washed with dichloromethane (10 mL × 2), and the filtrate and the washing solution were combined. It was washed twice with saturated sodium chloride solution, and water was removed with anhydrous sodium sulfate. The solvent was distilled off and dried to obtain high-quality compound II-6, yield 100%. |
99% | With dihydrogen peroxide In lithium hydroxide monohydrate; butan-1-ol at 50℃; for 3h; | |
99% | With (Bu4N)2[{MoO(O2)2}2(μ-O)]; dihydrogen peroxide In acetonitrile for 24h; | 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 |
99% | With sodium (meta)periodate In dichloromethane; lithium hydroxide monohydrate; acetonitrile at 75℃; for 1h; | |
98% | With anhydrous potassium sulfate; sulfuric acid potassium salt; potassium peroxomonosulfate; wet-montmorillonite In dichloromethane for 3h; Ambient temperature; | |
98% | With potassium peroxomonosulfate; kaolin In dichloromethane for 5h; Ambient temperature; | |
98% | With dihydrogen peroxide In lithium hydroxide monohydrate at 80℃; for 5.08333h; Green chemistry; | 2.6. General procedure for catalytic oxidation of sulfides to sulfones General procedure: To a stirred solution of 5 mmol sulfide in 5 mL water, 0.01 mmol of Ti containing catalyst [PATi (2.81 mg) or PMATi (3.77 mg)] was added, followed by addition of 50% H2O2 (1.36 mL, 20 mmol) in a round bottom flask. The Ti: substrate molar ratio was maintained at 1 : 500 and the substrate: H2O2 molar ratio at 1 : 4. The reaction was conducted at 80 °C temperature. The reaction was monitored by thin-layer chromatography (TLC) and GC. After completion of the reaction, the system was allowed to cool to room temperature. The sulfone obtained was then isolated, purified and characterized by following similar procedure as mentioned under above section. |
98% | With oxygen at 100℃; for 20h; Schlenk technique; chemoselective reaction; | |
97% | With dihydrogen peroxide In lithium hydroxide monohydrate at 20℃; for 1.33333h; Green chemistry; chemoselective reaction; | 2.4. General procedure for oxidation of sulfides General procedure: The catalytic protocol for the oxidation of sulfides was as follows:catalyst (0.005 mmol of Nb) [Catalyst 1 (16.7 mg) or Catalyst 2 (13.9mg)] and 5 mmol of the substrate was placed in a 50 mL two-neckedround-bottomed flask. With constant magnetic stirring at room temperature,50% H2O2 (0.68 mL, 10 mmol) was added to the reactionmixture. The molar ratio of Nb:MPS:oxidant was fixed at 1:1000:2000.Thin-layer chromatography (TLC) and GC were used to monitor theprogress of the reaction. As the reaction was completed, the catalyst wasseparated from the mixture by filtering and repeatedly washed withacetone. The unreacted organic substrates, also the products of the reactionwere extracted using diethyl ether and dried with anhydrousNa2SO4 subsequently distilled under reduced pressure to remove theexcess of diethyl ether. Column chromatography was carried out topurify the products where ethyl acetate:hexane (1:9) was used as themobile phase. IR, NMR spectral analysis, and melting point determinationwere mainly applied for the characterization of the obtainedproducts. |
96% | With oxygen In phosphate buffer; <i>tert</i>-butyl alcohol at 55℃; for 10h; | |
96% | With potassium peroxomonosulfate In methanol; lithium hydroxide monohydrate at 0 - 20℃; for 16h; | |
96% | With dihydrogen peroxide In acetonitrile at 20℃; for 0.5h; | |
95% | With dihydrogen peroxide In lithium hydroxide monohydrate at 20℃; for 10h; | |
95% | With oxygen; epi-Cercosporin In methanol at 25℃; for 24h; Irradiation; | 5 Example 5 Catalytic Synthesis of 4-Bromo-Phenyl methyl Sulfone by Cercosporin Catalyst In a 10 mL reaction tube, cercosporin (0.005 mmol) and 4-bromo-phenyl methyl sulfide (0.5 mmol) were sequentially added.2mL of methanol, then oxygen protection, 15W white light irradiation, room temperature 25 ° C reaction for 24h.Rapid object separated by thin layer silica gel plates 300-500 The reaction solution was evaporated to dryness using a rotary evaporator the solvent used is acetic acid eluent ethyl acetate / petroleum ether (v: v = 1: 5),4-Bromo-phenyl methyl sulfone was obtained in a yield of 95%. |
95% | With sodium (meta)periodate; ammonium acetate; C24H28ClN4O2Ru(1+)*F6P(1-) In dichloromethane; lithium hydroxide monohydrate; acetonitrile at 25℃; for 8h; | |
94% | With 1-butyl-3-methylimidazolium perrhenate; dihydrogen peroxide; 1-n-butyl-3-methylimidazolium tetrafluoroborate In lithium hydroxide monohydrate at 60℃; for 2h; Schlenk technique; Inert atmosphere; Green chemistry; | 2.3 Catalytic oxidation of sulfides General procedure: To a stirred solution of sulfide (10mmol) and [C4mim][ReO4] (0.1955g, 5 mol%) in [C4mim][BF4] (2mL), an aqueous solution of hydrogen peroxide (35% in water) (3.5mL, 40mmol) is added in 2-3 portions at 60°C. The progress of the reaction is followed by TLC. The reaction mixture is extracted with diethyl ether (5×10mL) and the extract is dried over anhydrous MgSO4. The yield and selectivity of methyl phenyl sulfone are calculated from calibration curves (r2>0.999) recorded using 3-methylanisole and 1,4-diacetylbenzene as internal standard. The crude product is obtained by rolling evaporation and purified by column chromatography separation (silica gel using hexane/ethyl acetate 90:10 v/v). The RTIL phase is diluted with CH2Cl2 and then treated with MnO2 to destroy the excess peroxide. The obtained liquid is first dried over anhydrous MgSO4 and then for 4h in vacuo at 50°C to remove CH2Cl2. Fresh substrate and hydrogen peroxide are then added for a new reaction cycle. All products are characterized by melting point, 1H NMR, 13C NMR and IR spectroscopy (see Supporting information). |
94% | With lithium hydroxide monohydrate; N-(benzenesulfonyl)-N-fluorobenzenesulfonamide at 50℃; for 24h; chemoselective reaction; | |
93% | With tert.-butylhydroperoxide; lanthanum(III) oxide In lithium hydroxide monohydrate; ethyl acetate at 150℃; for 5.5h; | |
91% | With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; Cooling with ice; | |
89% | With potassium permanganate; Rexyn 101 H ion exchange resin In dichloromethane for 6h; Heating; | |
88% | With dihydrogen peroxide In lithium hydroxide monohydrate; acetonitrile at 60℃; for 0.5h; | |
88% | With dihydrogen peroxide at 20℃; for 0.333333h; Green chemistry; chemoselective reaction; | |
88% | With diethylene glycol dibutyl ether; oxygen; sodium trifluoro-methanesulfinate at 20℃; for 48h; Irradiation; | |
86% | With dihydrogen peroxide In 1,2-dichloro-ethane for 0.416667h; Reflux; | |
86% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; 4-methoxyisoquinoline; oxygen; copper(II) sulphate In methanol at 65℃; for 72h; Schlenk technique; Sealed tube; Green chemistry; | 17 Example 17: Preparation of 4-bromophenyl methyl sulfone from 4-bromophenyl methyl sulfide TEMPO (3.9 mg, 0.025 mmol) was added to a 100 mL Schlenk reaction tube in turn. Methanol (1 mL), CuSO4 (4.0 mg, 0.025 mmol), 4-methoxyisoquinoline (39.8 mg, 0.25 mmol), 4-bromophenyl methyl sulfide(101.6 mg, 0.5 mmol), Filled with 1 atm of oxygen, The sealed reaction tube was heated to 65 ° C for 72 h. After completion of the reaction, the mixture was cooled to room temperature, and an appropriate amount of ethyl acetate was added, and a blue solid was precipitated from the reaction mixture, which was filtered, and the filtrate was concentrated under reduced pressure and purified by column chromatography. The product was obtained in a yield of 86%. |
85.8% | With sulfur(VI) fluoride; dihydrogen peroxide; potassium carbonate In methanol at 23 - 32℃; Sealed tube; | 12 Example 12: Synthesis of 4-bromophenylmethyl sulfone Add 4 mL of methanol to a 25 mL round bottom two-necked flask, then add 4-bromoanisole (0.5mmol, 62.1mg), then add 30% H2O2 (6.0eq., 0.3mL), potassium carbonate (4.0eq., 276.4 mg), using two straight piston straight-bending joints at the same time, while connecting the balloon with a hose, while injecting SO2F2 gas, stirring and reacting at room temperature of 2332 for 2040min under sealed conditions. After the reaction, the solid potassium carbonate was removed by filtration, dried with anhydrous sodium sulfate to remove water and filtered again. The solvent was concentrated to obtain a crude product, which was finally separated and purified by column chromatography to obtain 99.3 mg of 4-bromophenylmethyl sulfone with a yield of 85.8 %. |
84% | With diethylene glycol dibutyl ether; oxygen at 110℃; for 20h; | |
80% | With tetra-n-butylammonium tetrafluoroborate; oxygen In dichloromethane at 20℃; for 10h; Electrochemical reaction; Green chemistry; | |
79% | With lithium hydroxide monohydrate In acetonitrile at 20℃; Electrochemical reaction; Flow reactor; | |
75% | With potassium permanganate supported on montmorillonite K10 at 20℃; for 3h; | |
75% | With potassium peroxomonosulfate In methanol; lithium hydroxide monohydrate at 5 - 20℃; for 5h; | |
73% | With diethylene glycol dibutyl ether; oxygen at 150℃; Green chemistry; | |
59% | With tetra-n-butylammonium tetrafluoroborate; lithium hydroxide monohydrate In methanol at 25℃; for 10h; Electrochemical reaction; | |
55% | With Benzo<c>thioxanthon; oxygen In acetonitrile at 20℃; Sealed tube; Irradiation; | General procedure E to the synthesis of sulfones General procedure: A solution of sulfides 1 (0.2 mmol, 1.0 equiv) or sulfoxides 2 (0.2 mmol, 1.0 equiv), photocatalyst (c, 5 mol%), and ACN (1 mL, 0.2 M) was sealed in an oven-dried reaction tube equipped with an oxygen balloon (gas-switch three times with oxygen balloon). The reaction was agitated under 18 W 405 nm LEDs at room temperature for 12 to 24 h. The progress of the reaction was monitored by GC-MS or/and TLC. After completion of the reaction, the solvent was removed under reduced pressure, and the crude product 3 was purified by flash silica chromatography using n-hexane and ethyl acetate as eluent (v/v, 80:20). |
52% | With hydrogenchloride; tetra-n-butylammonium perchlorate; oxygen In lithium hydroxide monohydrate; acetonitrile for 0.166667h; Electrochemical reaction; Flow reactor; Green chemistry; | |
51% | With potassium peroxomonosulfate In lithium hydroxide monohydrate; propan-2-one at 20℃; for 16h; | 1013.2 Step-2: Synthesis of 1-bromo-4-(methylsulfonyl)benzene To a stirred solution of (4-bromophenyl)(methyl)sulfane (0.5 g, 2.47 mmol) in acetone (10 mL) was added Oxone(0.76 g, 2.47 mmol) in water (5mL) then, reaction mass was stirred at room temperature for 16h. Reaction was monitored by TLC. On completion reaction was concentrated under reduced pressure and extracted with ethyl acetate. The organic layer was washed with water, brine, dried over sodium sulphate, concentrated under reduced pressure obtained 1-bromo-4-(methylsulfonyl)benzene (0.3g, 51%) as light brown solid. MS: 235.17[M++1] |
45% | With 3-chloro-benzenecarboperoxoic acid In dichloromethane | 65 To a solution of 4-bromothioanisole (22.3 g, 11 mmol) in DCM (250 ml) was added m-chloroperoxybenzoic acid (40 g, 23 mmol) in 10 g portions. The precipitate was removed by filtration and washed with DCM. The filtrate was evaporated in vacuo and the resultant solid recrystallized from EtOH (c.a 180 ml) to yield the title compound as colourless crystals 11.7 g (45%). Mp 103-106° C. |
With permanganate(VII) ion; glacial acetic acid | ||
With lithium hydroxide monohydrate; permanganate(VII) ion | ||
With dihydrogen peroxide; glacial acetic acid | ||
With potassium permanganate; glacial acetic acid | ||
With dihydrogen peroxide In glacial acetic acid | ||
With manganese sulphate; dihydrogen peroxide; Sodium hydrogenocarbonate In acetonitrile at 20℃; for 24h; | ||
With potassium peroxomonosulfate In methanol | ||
Multi-step reaction with 2 steps 1.1: aq. hydrogen peroxide; MnSO4*H2O / acetonitrile / 24 h / 20 °C 2.1: VO(acac)2; (R)-diiodo Shiff base ligand / CHCl3 / 1 h / 22 °C 2.2: aq. hydrogen peroxide / CHCl3 / 20 h / 0 °C | ||
With hydrated [2-percarboxyethyl]-functionalized silica In carbon dioxide at 40℃; for 3h; Supercritical conditions; Autoclave; liquid CO2; chemoselective reaction; | ||
With dihydrogen peroxide In chloroform-d1; lithium hydroxide monohydrate at 35℃; for 0.25h; | ||
With dihydrogen peroxide In lithium hydroxide monohydrate at 20℃; for 24h; Green chemistry; chemoselective reaction; | ||
With (dimethyl dioctadecylammonium)7[PW11O39]; dihydrogen peroxide In 1,4-dioxane; lithium hydroxide monohydrate at 59.84℃; for 0.5h; | 2.3. Catalytic reaction General procedure: Catalyst (8 μmol), 1,4-dioxane (2 ml), substrate (1 mmol), and H2O2( 2.5 mmol, 30% aq.) were charged in the reaction flask. The reaction was carried out at 333 K for 0.5 h. After reaction, with the dropping of temperature, the catalyst gradually precipitated from solution. It was separated by centrifugation and washed with Et2O, then dried under vacuum and used for the next oxidation cycle. The filtrate was analyzed by GC using bromobenzene as internal standard. The organic products were obtained by vacuum rotary evaporator, and identified by 1H NMR. | |
With Na10K22[Zr24O22(OH)10(H2O)2(W2O10H)2(GeW9O34)4(GeW8O31)2]*85H2O; dihydrogen peroxide In dodecane; acetonitrile at 60℃; for 1h; Sealed tube; | ||
With lithium hydroxide monohydrate; dihydrogen peroxide; molybdenum(VI) oxide at 20℃; for 18h; Ionic liquid; | ||
With dihydrogen peroxide In lithium hydroxide monohydrate at 20℃; for 3h; Green chemistry; | ||
With dihydrogen peroxide In acetonitrile at 35℃; for 2.3h; Green chemistry; | General procedure for oxidation of sulfides General procedure: The oxidation of sulfides was performed in a round-bottom flask containing a mixture of sulfide (1 mmol), H2O2 (2 mmol) and catalyst (1 mol%, 17 mg based on AAS) at room temperature (Scheme 2). Progress of the reaction was monitored by TLC. After completion of the reaction,the catalyst was separated by external magnet, washed with water/ethanol and reused for subsequent recycling runs. The products were extracted by CH2Cl2. Evaporation of CH2Cl2 under vacuum gave corresponding sulfoxides or sulfones. | |
With 5Na(1+)*10K(1+)*17H(1+)*54H2O*Sc6Sb2W6O19(22+)*6SbW9O33(9-); dihydrogen peroxide In acetonitrile at 80℃; for 3h; | ||
With 6C16H36N(1+)*(x)H2O*Mo7O26(6-); dihydrogen peroxide In acetonitrile at 22℃; for 4h; | ||
With 22C2H7N*22H(1+)*124H2O*18Na(1+)*2Ti7O6(SbW9O33)4(20-); dihydrogen peroxide In acetonitrile at 60℃; for 1h; | ||
With C4H12NO(1+)*4C2H8N(1+)*3H(1+)*4Na(1+)*2Ce(3+)*32H2O*C4H11NO*3SeW9O33(8-)*W4O9(6+); dihydrogen peroxide In acetonitrile at 40℃; for 1h; | ||
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 0 - 20℃; for 16h; | 438 Example 438 [002088] Synthesis of 4-(((trans)-4-(4-(methylsulfonyl)phenyl)cyclohexyl)oxy)-lH- l,2,3-triazole-5-carboxylic acid (438) To a solution of (4-bromophenyl)(methyl)sulfane (438A, 4.5 g, 22.17 mmol) in dichloromethane (100 mL) was added m-chlorobenzoperoxoic acid (11.44 g, 66.51 mmol) in several portions at 0 °C, stirred at room temperature for 16 hours, and filtered. The filtrate was washed with saturated aqueous NaHCCb solution (60 mL x 2) and brine (60 mL), dried over anhydrous sulfate, filtered, concentrated, and purified with flash column chromatography on silica gel (ethyl acetate in petroleum ether, from 0% to 40% v/v) to furnish Compound 438B. LC-MS (ESI) m/z: 235 [M+H]+; 1H-NMR (CDCb, 400 MHz): d (ppm) 3.05 (s, 3H), 7.72 (d, J = 8.4 Hz, 2H), 7.81 (d, J= 8.8 Hz, 2H). | |
With dihydrogen peroxide; 2O33SbW9(9-)*53H2O*4C2H7N*8.5H(1+)*11.5Na(1+)*[Zr4W8Sb4P5O49(OH)5](2-) In acetonitrile at 45℃; for 1h; | ||
With dihydrogen peroxide In lithium hydroxide monohydrate; acetonitrile at 50℃; for 0.5h; | 3. Experimental method for catalytic oxidation of various thioethers by catalyst 2a General procedure: The catalytic oxidation reactions of the various thioethers was performed in a 25-mL glass round bottom flask connected to a refluxing condenser under magnetic stirring at room temperature which was heated (50°C). The desired amount of catalyst 2a was added into the flask, along with 1mL of acetonitrile solution containing thioether and oxidant. The reaction vessel was sealed and stirred into a thermostatted oil bath. Reaction progress was monitored by TLC and gas chromatography. After the reaction, the vessel was cooled to room temperature and extracted with ethyl acetate for GC analysis. The thioether oxidation products (sulfoxide and sulfone) were identified with GC-MS and quantified using gas chromatography with internal standard techniques. | |
With dihydrogen peroxide; 19K(1+)*7Na(1+)*68H2O*((Dy2SiW10O38)4(W3O8)(OH)4(H2O)2)(26-) In lithium hydroxide monohydrate; acetonitrile at 50℃; for 0.5h; Sealed tube; | ||
With 64H2O*21Na(1+)*10H(1+)*4CO3(2-)*[(AsO4){Ni8(OH)6(SiW9O34)2}2](23-) at 70℃; for 2h; | ||
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 0 - 20℃; for 16h; | 438 Synthesis of 4-(((trans)-4-(4-(methylsulfonyl)phenyl)cyclohexyl)oxy)-1H- 1,2,3-triazole-5-carboxylic acid (438) To a solution of (4-bromophenyl)(methyl)sulfane (438A, 4.5 g, 22.17 mmol) in dichloromethane (100 mL) was added m-chlorobenzoperoxoic acid (11.44 g, 66.51 mmol) in several portions at 0 oC, stirred at room temperature for 16 hours, and filtered. The filtrate was washed with saturated aqueous NaHCO3 solution (60 mL x 2) and brine (60 mL), dried over anhydrous sulfate, filtered, concentrated, and purified with flash column chromatography on silica gel (ethyl acetate in petroleum ether, from 0% to 40% v/v) to furnish Compound 438B. LC-MS (ESI) m/z: 235 [M+H]+; 1H-NMR (CDCl3, 400 MHz): d (ppm) 3.05 (s, 3H), 7.72 (d, J = 8.4 Hz, 2H), 7.81 (d, J = 8.8 Hz, 2H). | |
With dihydrogen peroxide; 3C2H7N*20H2O*4Na(1+)*12H(1+)*Ti6W4O18(OH)(H2O)3(11+)*3SbW9O33(9-) In acetonitrile at 60℃; for 1h; | ||
With dihydrogen peroxide; DyH8O80P2W20Zn4(11-)*23H2O*11K(1+) In lithium hydroxide monohydrate; acetonitrile at 40℃; for 1h; | ||
With dihydrogen peroxide; O117Si3Ti6W30(18-)*9C2H7N*18H(1+)*11H2O In acetonitrile at 60℃; for 0.666667h; | ||
With dihydrogen peroxide; C15H30N5O10Ta In methanol; lithium hydroxide monohydrate at 20℃; for 2h; Inert atmosphere; Sealed tube; | 2.2 Catalytic reactions General procedure: General procedure. 0.5mmol of sulfide and 1.0mL of solvent (methanol or acetonitrile, concentration 0.5M) were introduced into a 3mL vial, then dinitrogen was fluxed for ca. 3 minutes. Then, while keeping the vial under a cone under N2 flux, the catalyst (1.0mol %) and the appropriate amount (2.0 or 3.0 equiv.) of 30% aqueous solution of hydrogen peroxide were added to the mixture. The sealed vial was either thermostated at 45°C through an oil bath or left at room temperature, under stirring. After 1.5 or 2.0h (in relation to the substrate), additional equivalent of oxidant was added dropwise when necessary. At the end of the reaction, the mixture was treated with 5.0mg of MnO2 to quench the excess of oxidant and, after 10 minutes, filtered. The progress of the reaction was monitored through GC-FID analysis, by withdrawing an aliquot of 20 μL and adding 5 μL of n-hexadecane (internal standard). The oxidation products were identified by comparison of their GC retention times with those of authentic samples. | |
With dihydrogen peroxide In lithium hydroxide monohydrate; acetonitrile at 40℃; for 1h; Green chemistry; | ||
With thio-xanthene-9-one; oxygen In butanone at 35 - 40℃; for 24h; 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 by flash column chromatography on silica gel to give the corresponding sulfone2. | |
With dihydrogen peroxide; 28Na(1+)*70H2O*(Pr4As2O6(OH)2WO(WO3)2(AsW9O33)4)(28-) In lithium hydroxide monohydrate; acetonitrile at 40℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | Stage #1: (4-bromophenyl)thioanisole With iodine; magnesium; ethylene dibromide In diethyl ether Stage #2: chloro-trimethyl-silane In diethyl ether Reflux; | 4.2.1. 4-tert-Butylphenyltrimethylsilane 1 (R=tBu) General procedure: This derivative was prepared by the method outlined by Eaborn.36 C. Eaborn, J. Chem. Soc. (1956), pp. 4858-4864. Full Text via CrossRef36 To Mg turnings (2.05 g, 85.5 mmol) suspended with stirring in dry ether (50 mL) was rapidly added 1-bromo-4-tert-butylbenzene (15.2 g, 71.0 mmol) in dry ether (50 mL). A small amount of iodine and 1,2-dibromoethane (3 drops) were added to initiate the reaction, and dry ether (100 mL) was then rapidly added. When formation of the Grignard reagent was complete, trimethylsilyl chloride (7.74 g, 71.0 mmol) in dry ether (50 mL) was added over 30 min. The mixture was then stirred and heated under reflux overnight. Most of the solvent was then evaporated and the residue treated with satd aq NH4Cl solution (50 mL). The ether layer was separated and the aqueous layer extracted with ether (2×50 mL). The combined ether layers were dried (MgSO4) and evaporation gave a solid product, which after recrystallisation from EtOH/H2O was identified as compound 1 (R=tBu) (12.2 g, 83%), colourless crystals, mp 78 °C [lit.,36 78 °C]; 1H NMR (CDCl3) δ 0.31 (s, 9H, SiMe3), 1.37 (s, 9H, CMe3) and 7.48 (dd J 8.3 Hz, 4H, ArH); IR (KBr) νmax/cm-1 3050, 2960, 1250, 838 and 759; MS (EI) m/z 206 (M+) (10%), 191 (100%). Anal. Calcd for C13H22Si: C, 75.65; H, 10.74. Found: C, 75.70; H, 10.70%. |
75% | Stage #1: (4-bromophenyl)thioanisole With n-butyllithium In diethyl ether; hexane at 0℃; for 2h; Stage #2: chloro-trimethyl-silane In diethyl ether; hexane at 0 - 20℃; Further stages.; | |
44% | Stage #1: (4-bromophenyl)thioanisole With n-butyllithium In tetrahydrofuran; n-Pentane at -78℃; for 1h; Inert atmosphere; Stage #2: chloro-trimethyl-silane In tetrahydrofuran; n-Pentane at -78 - 20℃; for 18h; Inert atmosphere; |
With magnesium In N,N,N,N,N,N-hexamethylphosphoric triamide | ||
(i) Mg, (ii) /BRN= 1209232/; Multistep reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With bis(bipyridine)nickel(II) bromide; ethylene dibromide; sodium iodide In N,N-dimethyl-formamide at 20℃; for 4h; Electrochemical reaction; Inert atmosphere; | General procedure: DMF (40 mL), NaI (375 mg, 2.5 mmol), and 1,2-dibromoethane (100μL, 1.16 mmol) were added to an undivided electrochemical cell, fitted with an iron/nickel (64/36) anode, and surrounded by a nickel foam as the cathode (surface: 40 cm2, porosity: 500 μm, Goodfellow).The mixture was electrolyzed under argon at a constant current intensityof 0.2 A at r.t. for 15 min. The current was then stopped, then NiBr2bpy (187 mg, 0.5 mmol) and aryl or heteroaryl halide (5 mmol),were sequentially added. The solution was electrolyzed at 0.2 A untilthe starting aryl or heteroaryl halide had been totally consumed (2-5h). Sat. aq EDTA-Na2 solution (50 mL) was added, and the resultingsolution was extracted either with EtOAc (for aryl halides) or withCH2Cl2 (for heteroaryl halides) (3 × 50 mL). The combined organic layerswere washed with brine (50 mL), dried (MgSO4), filtered, and concentratedunder vacuum. The crude product was purified by flashchromatography (silica gel, 70-200 μm). |
With NaH-t-AmONa-Ni(OAc)2-bpy-KI In tetrahydrofuran; benzene at 63℃; for 2.5h; Yield given; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With MoO(O2)2(H2O); C15H24N2O4; dihydrogen peroxide; tetraphenylphosphonium bromide In chloroform; water at 0℃; for 1h; enantioselective reaction; | 3.5. General Procedure for Enantioselective Mo-Catalyzed Oxidation of Sulfides in the Presence of HLR General procedure: The reactor (a 50 mL vial equipped with a Young valve and containing a stirrer flea) was charged with [Mo(O)(O2)2(H2O)n] (100 μL, 0.25 M aqueous solution, 0.025 mmol), HLR (0.0125 mmol), [PPh4]Br as specified (typically 0.05 mmol), the reaction solvent (1 mL), the oxidant (30% aqueous H2O2; 1 mmolper sulfide substrate, see details above) and the sulfide substrate (1 mmol), in the aforementioned order.The reactor was sealed and maintained at the working temperature, with constant stirring (600 rpm)in a thermostatted bath for the duration of the reaction. Upon completion, the reaction mixture wastreated with diethyl ether (10 mL) and then filtered with 0.45 μm nylon syringe filter. The resultingsolution was analyzed by GC (by adding 50 μL of dodecane as the internal standard). Afterwards thesolution was evaporated to dryness by using a rotavap. The resulting residue was then analyzed by HPLC (by adding 20 mL of ethyl acetate). |
17% | With C43H65N4O4Ti(1+)*Cl(1-); dihydrogen peroxide In water at 25℃; for 1h; Green chemistry; enantioselective reaction; | |
With titanium(IV) isopropylate; tert.-butylhydroperoxide; diethyl (2R,3R)-tartrate In dichloromethane at -20℃; for 4h; Yield given. Yields of byproduct given; |
With titanium(IV) isopropylate; tert.-butylhydroperoxide; (S,S)-hydrobenzoin; water 1.) CCl4, RT, 15 min, 2.) CCl4, H2O, 0 deg C, 2 h; Yield given. Multistep reaction. Yields of byproduct given. Title compound not separated from byproducts; | ||
With titanium(IV) isopropylate; diethyl (2R,3R)-tartrate; 5-(1-hydroxyethyl)-2-methyl-3-furoic acid 5α-cholestan-3β-yl ester In dichloromethane at -20℃; for 2h; Yield given. Yields of byproduct given. Title compound not separated from byproducts; | ||
With (S,S)-β-oxo aldiminato Mn(III); oxygen; pivalaldehyde In xylene Ambient temperature; Yield given. Yields of byproduct given. Title compound not separated from byproducts; | ||
With (S,S)-β-oxoaldiminatoMn(III) complex B; oxygen; pivalaldehyde In m-xylene for 20h; Ambient temperature; Yield given. Title compound not separated from byproducts; | ||
With titanium(IV) isopropylate; diethyl (2R,3R)-tartrate; 5-(1-hydroxyethyl)-2-methyl-3-furoic acid 5α-cholestan-3β-yl ester In dichloromethane at -20℃; for 2h; Yield given. Yields of byproduct given. Title compound not separated from byproducts; | ||
With titanium(IV) isopropylate; tert.-butylhydroperoxide; (R,R)-hydroxybenzoin In tetrachloromethane; water at 0℃; for 2h; Yield given; Yields of byproduct given. Title compound not separated from byproducts; | ||
With titanium(IV) isopropylate; tert.-butylhydroperoxide; (S,S)-4,4'-bis(3-hydroxy-estra-1,3,5(10),6,8-pentaene); water In tetrahydrofuran Yield given; Yields of byproduct given. Title compound not separated from byproducts; | ||
With di(2-methoxybenzoyl)-L-tartaric acid; iodoxybenzene; cetyltrimethylammonim bromide In water; toluene at 20℃; for 12h; | ||
With Cumene hydroperoxide; (R)-(+)-5,5',6,6',7,7',8,8'-octafluoro-2,2'-dihydroxy-1,1'-binaphthyl In chloroform at 20℃; for 18h; | ||
With 4 A molecular sieve; asymmetric Shiff base; urea-hydrogen peroxide In dichloromethane at -10℃; for 48h; Title compound not separated from byproducts; | ||
With iron(III)-acetylacetonate; (S)-(-)-2-(N-3,5-diiodosalicylidene)amino-3,3-dimethyl-1-butanol; dihydrogen peroxide In dichloromethane at 20℃; for 16h; Title compound not separated from byproducts; | ||
With chiral Schiff base derived from (R)-BINOL and (S)-t-leucinol; dihydrogen peroxide In dichloromethane at 0℃; for 24h; Title compound not separated from byproducts; | ||
With bis(acetylacetonate)oxovanadium; (R,S)-Schiff-base ligand; dihydrogen peroxide In dichloromethane; water at 0℃; for 24h; Title compound not separated from byproducts; | ||
With iodosylbenzene In dichloromethane at 20℃; for 5h; Title compound not separated from byproducts; | ||
With titanium(IV) isopropylate; tert.-butylhydroperoxide; (R,R)-hydroxybenzoin In tetrachloromethane at 0℃; for 2h; Title compound not separated from byproducts.; | ||
With titanium(IV) isopropylate; Cumene hydroperoxide In dichloromethane at -20℃; for 16h; Title compound not separated from byproducts.; | ||
With dihydrogen peroxide In dichloromethane at 20℃; for 16h; Title compound not separated from byproducts.; | ||
With iodosylbenzene; C75H102Cl3Fe3N6O6 In dichloromethane at 20℃; for 15h; optical yield given as %ee; enantioselective reaction; | ||
With MoO2(O((C6H2)(C(CH3)3)2)CHNCH(C6H5)CH2O)(CH3OH); dihydrogen peroxide In chloroform at 0℃; for 15h; optical yield given as %ee; enantioselective reaction; | ||
With bis(acetylacetonate)oxovanadium; 2,4-bis(1,1-dimethylethyl)-6-([(1S)-1-hydroxymethyl-2,2-dimethylpropyl]imino}methyl)phenol; dihydrogen peroxide In dichloromethane at 0℃; for 20h; optical yield given as %ee; enantioselective reaction; | ||
With titanium(IV) isopropylate; (S)-2-[N-{3,5-bis(α,α-dimethylbenzyl)salicylidene}amino]-3,3-dimethyl-1-butanol; dihydrogen peroxide In dichloromethane; water at 20℃; for 3h; optical yield given as %ee; enantioselective reaction; | ||
Stage #1: (4-bromophenyl)thioanisole With (R)-(3,3'-bis(1-naphthyl)-1,1'-binaphthanele-2,2'-yl)phosphoric acid In chloroform at -40℃; for 0.5h; Stage #2: With dihydrogen peroxide In chloroform; water at -40℃; for 115h; optical yield given as %ee; enantioselective reaction; | ||
With bis(acetylacetonate)oxovanadium; 2,4-di-tert-butyl-6-{2-[2,2-dimethyl-cyclopent-3-enyl]-2-hydroxypropylideneamino}phenol; dihydrogen peroxide In dichloromethane; water at 20℃; for 2h; optical yield given as %ee; enantioselective reaction; | ||
With BF4(1-)*C25H39N4O3V(1+); dihydrogen peroxide In dichloromethane; water at 20℃; for 4h; optical yield given as %ee; enantioselective reaction; | ||
86 % ee | With titanium(IV) isopropylate; Cumene hydroperoxide; C22H30O12 In dichloromethane; water at -20℃; for 1h; Inert atmosphere; Overall yield = 88 %; enantioselective reaction; | |
82 % ee | With bis(acetylacetonate)oxovanadium; (1S,2R)-2-((5-ethylthiophen-2-yl)methyleneamino)-1-phenylpropan-1-ol; dihydrogen peroxide In dichloromethane; water at 0℃; for 10.5h; Inert atmosphere; Overall yield = 93 %; enantioselective reaction; | 4.3. A general procedure for the asymmetric oxidation of thioanisole General procedure: Compound VO(acac)2 (2.7 mg, 0.01 mmol) and chiral ligand (0.015 mmol) were dissolved in CH2Cl2 (1 mL). The mixture was stirred for 30 min under an argon atmosphere at 0 °C. A solution of sulfide (1.0 mmol) in CH2Cl2 (1 mL) was then added, followed by dropwise addition (ca. 30 min) of aqueous H2O2 (30%, 1.2 mmol) at 0 °C. The reaction progress was monitored by TLC analysis. After the mixture was stirred at 0 °C for 10 h, the resulting solution was extracted with CH2Cl2. The organic layer was washed with brine and dried over Na2SO4. Filtration and evaporation gave a residue which was purified by flash chromatography on silica gel with petroleum ether/ethyl acetate (3:2, v/v) and ethyl acetate as eluents. The pure sulfoxide was obtained after removal of the solvent by rotary evaporation. The adducts were fully characterized by comparison of their spectroscopic data with those reported in the literature. The enantiomeric purity of the product was determined by HPLC analysis. The absolute configuration of the products was assigned by comparison to the literature data.27,29b,37 |
65 % ee | With bis(acetylacetonate)oxovanadium; (1R,2S)-2-(5-ethylthiophen-2-yl)methylamino-1-phenylpropanol; dihydrogen peroxide In dichloromethane; water at 0℃; for 10.5h; Inert atmosphere; Overall yield = 80 %; enantioselective reaction; | 4.3. A general procedure for the asymmetric oxidation of thioanisole General procedure: Compound VO(acac)2 (2.7 mg, 0.01 mmol) and chiral ligand (0.015 mmol) were dissolved in CH2Cl2 (1 mL). The mixture was stirred for 30 min under an argon atmosphere at 0 °C. A solution of sulfide (1.0 mmol) in CH2Cl2 (1 mL) was then added, followed by dropwise addition (ca. 30 min) of aqueous H2O2 (30%, 1.2 mmol) at 0 °C. The reaction progress was monitored by TLC analysis. After the mixture was stirred at 0 °C for 10 h, the resulting solution was extracted with CH2Cl2. The organic layer was washed with brine and dried over Na2SO4. Filtration and evaporation gave a residue which was purified by flash chromatography on silica gel with petroleum ether/ethyl acetate (3:2, v/v) and ethyl acetate as eluents. The pure sulfoxide was obtained after removal of the solvent by rotary evaporation. The adducts were fully characterized by comparison of their spectroscopic data with those reported in the literature. The enantiomeric purity of the product was determined by HPLC analysis. The absolute configuration of the products was assigned by comparison to the literature data.27,29b,37 |
83 % ee | With C170H240N22O16Ti4(4+)*4Cl(1-); dihydrogen peroxide In dichloromethane at 20℃; for 3h; Overall yield = 89 %Chromat.; enantioselective reaction; | |
89 % ee | With dihydrogen peroxide In water at 25℃; for 0.983333h; Overall yield = 85%; enantioselective reaction; | 2.4 General procedure for asymmetric oxidation of sulfides to sulfoxides General procedure: The selected catalyst (0.5mol% substrate, based on the titanium content in catalyst) and methyl aryl sulfides (1.0mmol) were added to H2O (1mL) under stirring at 25°C. H2O2 (30wt%, 1.2mmol) was then dropwise added within 15min. The resulting mixture was stirred at room temperature until the reaction was judged to be complete based on GC analysis. Then, the reaction mixture was heated to 40°C. Catalyst was precipitated out from the reaction system completely, washed with n-hexane (3×5mL), dried in a vacuum, and finally recharged with fresh substrate and oxidant for the next catalytic cycle. The supernatants separated from reaction system were extracted with dichloromethane thrice. Combined organic phase was concentrated in vacuum. Further purification of the residue by chromatography on silica gel (petroleum ether/ethyl acetate, 1.5/1) afforded pure sulfoxides. The pure sulfoxides have been identified by 1H NMR and 13C NMR spectra. The conversion and chemoselectivity of chiral sulfoxides were measured by a 6890N gas chromatograph (Agilent Co.) equipped with a capillary column (HP19091G-B213, 30m×0.32mm×0.25μm) and a FID detector. Ee values of corresponding chiral sulfoxides were determined by HPLC analysis using the Daicel chiralpak AD columns. Detailed NMR spectra and HPLC analysis for sulfoxides are available in the ESI.† |
57 % ee | Stage #1: (4-bromophenyl)thioanisole With C28H72N8O20V8*7CH4O; bovine serum albumin In aq. phosphate buffer for 5h; Green chemistry; Stage #2: With tert.-butylhydroperoxide In aq. phosphate buffer at 20℃; for 8h; Green chemistry; Overall yield = 95 %; enantioselective reaction; | |
60 % ee | With dihydrogen peroxide; acetic acid In methanol; water at 0℃; for 12h; Overall yield = 87 %; enantioselective reaction; | 2.3. Catalytic oxidation of sulfides to sulfoxides General procedure: The appropriate catalyst 5 (10 mol%) and sulfide (1.0 mmol) were dissolved in CH3OH/H2O (1:1) (5 mL) and this solution was cooled to 0 °C. Subsequently the additive HOAc (2.0 mmol) and the oxidant hydrogen peroxide (1.5 mmol, 30%, w/w) were added. The mixture was stirred for 12 h and then was treated with 10 mL of saturated ammonium chloridesolution and extracted with ethyl acetate. The organic layer was dried (MgSO4), filtered and concentrated to give pure sulfoxides through flash column chromatography on silica gel (hexane/ethyl acetate(10:1)). All the products in the paper are known compounds that exhibited spectroscopic data identical to those reported in the literature [34]. The ee was determined by HPLC on chiral column (Daicel,Chiralpak, OD-H). The configuration of sulfoxides product from these reactions was proven to be (S) by comparing the specific rotation with the literature values [35]. |
12 % ee | With tert.-butylhydroperoxide; porcine serum albumin; C20H22N2O3V; 2-amino-2-hydroxymethyl-1,3-propanediol In aq. phosphate buffer; dimethyl sulfoxide at 20℃; for 20h; Overall yield = 91 %; enantioselective reaction; | Typical experimental procedure for enantioselective sulfoxidation reaction General procedure: The typical experimental procedure for enantioselective sulfoxidation reaction was: SA (2.7μmol, 176mg) was mixed for 1h at room temperature with ML standard stock solutions (2.7μmol, 53.3μL) through a simple mechanical stirring in 2mL 50mM PB (phosphate buffer) solution. 0.27mmol sulfide was added to the reaction mixture and the stirring was continued for 5 hours. The oxidant (1.5 equiv.) was then added to the solution in one portion and the reaction mixture stirred for another 10h at room temperature. Finally, the saturated sodium sulfite solution (Na2SO3) was added to quench the remaining H2O2. The aqueous solution was extracted with dichloromethane (CH2Cl2, 2ml×5). The combined organic solutions were dried over by anhydrous sodium sulfate (Na2SO4), filtered, and evaporated under vacuum. The same procedure was followed with ML or SAs alone. A sample of the crude reaction mixture re-dissolved in a minimum amount of isopropanol before being analyzed by HPLC with Chiralcel OB-H (4.6Φ mm×250mm) column (Daicel Chemical Industries, Tokyo) at room temperature. The enantiomeric excess (ee) was calculated using the formulas: ee%=[peak area (S-R)/(S+R)]×100%; reaction yields were measured by comparing the peak area ratios of the HPLC chromatograms of unreacted sulfide and produced sulfoxide; the absolute configurations of the sulfoxides were assigned by comparison of HPLC elution orders and sign of optical rotation reported in the literature. |
66 % ee | With (bis(α-ethylsalicylaldehyde)ethylenediiminato)cobalt(II); dihydrogen peroxide; 2-amino-2-hydroxymethyl-1,3-propanediol; bovine serum albumin In aq. phosphate buffer; dimethyl sulfoxide at 20℃; for 20h; Overall yield = 44 %; enantioselective reaction; | Typical experimental procedure for enantioselective sulfoxidation reaction General procedure: The typical experimental procedure for enantioselective sulfoxidation reaction was: SA (2.7μmol, 176mg) was mixed for 1h at room temperature with ML standard stock solutions (2.7μmol, 53.3μL) through a simple mechanical stirring in 2mL 50mM PB (phosphate buffer) solution. 0.27mmol sulfide was added to the reaction mixture and the stirring was continued for 5 hours. The oxidant (1.5 equiv.) was then added to the solution in one portion and the reaction mixture stirred for another 10h at room temperature. Finally, the saturated sodium sulfite solution (Na2SO3) was added to quench the remaining H2O2. The aqueous solution was extracted with dichloromethane (CH2Cl2, 2ml×5). The combined organic solutions were dried over by anhydrous sodium sulfate (Na2SO4), filtered, and evaporated under vacuum. The same procedure was followed with ML or SAs alone. A sample of the crude reaction mixture re-dissolved in a minimum amount of isopropanol before being analyzed by HPLC with Chiralcel OB-H (4.6Φ mm×250mm) column (Daicel Chemical Industries, Tokyo) at room temperature. The enantiomeric excess (ee) was calculated using the formulas: ee%=[peak area (S-R)/(S+R)]×100%; reaction yields were measured by comparing the peak area ratios of the HPLC chromatograms of unreacted sulfide and produced sulfoxide; the absolute configurations of the sulfoxides were assigned by comparison of HPLC elution orders and sign of optical rotation reported in the literature. |
89 % ee | With GO-IL-Ti(salen) In water at 20℃; enantioselective reaction; | |
With C60H88N4O10Ti2; dihydrogen peroxide In water at 25℃; for 1h; Optical yield = 91 %ee; | ||
With titanium(III) chloride; indole monooxygenase from Acinetobacter baylyi ADP1; dihydrogen peroxide In methanol; water at 20℃; for 0.416667h; Enzymatic reaction; | ||
With titanium(III) chloride; styrene monooxygenase from Gordonia polyisoprenivorans NBRC 16320; dihydrogen peroxide In methanol; water at 20℃; for 0.416667h; Enzymatic reaction; | ||
77 % ee | With dihydrogen peroxide; C96H140N8O10Ti2 In ethanol at 25℃; for 1h; Darkness; | |
85 % ee | With dihydrogen peroxide In water at 25℃; | |
82 % ee | Stage #1: (4-bromophenyl)thioanisole With titanium(IV) isopropylate; water; (R)-6,6'-dibromo-1,1'-binaphth-2-ol In toluene at 25℃; for 1h; Stage #2: With tert.-butylhydroperoxide In water; toluene at 0 - 30℃; for 14h; Overall yield = 72 percent; Overall yield = 1.54 g; enantioselective reaction; | General Procedure for the Catalytic Oxidation of Sulfides (1a-1f) General procedure: To a solution of (R)-6,6'-dibromo-BINOL(0.72g, 1.62 mmol) in toluene (20 mL) were added Ti(OiPr)4(0.22 mL, 0.81 mmol), water (0.14 mL, 8 mmol) and stirred for 30 min at room temperature. To the resulting homogeneous solution was added methyl phenyl sulfide (2.0 g, 16.0 mmol), and the mixture was stirred at room temperature for 60 min. The solution was then cooled to 0-5°C, 70% aqueous TBHP solution (4.4 mL, 32 mmol) was added slowly and stirred at 0-5°C for 5 h. Increased the temperature to 25-30°C and stirred for 9 h. The reaction mixture was concentrated under reduced pressure to obtain the crude product. This was further purified by column chromatography (ethyl acetate, cyclohexane 1:1) to get 1.80 g, (80% yield), of (R)-methyl phenyl sulfoxide (1a).[α]20D = +136 (c=1.7 in acetone); lit: [α]D = +130 (c = 1.7 in acetone) for (R), 89% ee;1 1b to 1f were prepared in the same manner. |
4 % ee | With D-Glucose; Amycolatopsis methanolica Baeyer-Villiger monooxygenase; NADPH In methanol at 30℃; for 12h; Enzymatic reaction; | Enzymatic synthesis of (R)- and (S)-aryl sulfoxides General procedure: A 10 mL reaction mixture contained 30-100 mM substrates dissolvedin methanol (5% v/v), 1.5 equivalent of glucose, 10 mg GDH, 0.2 mMNADP+ at 30 C and 180 rpm. Reactions were started by addition of 10g•L-1 dry cells of AmBVMO (15 U•g-1) or RaBVMO (23 U•g-1). Sampleswere withdrawn from the reaction mixture at different time intervals,and then extracted with equal volume of ethyl acetate supplementedwith 1 mM dodecane as an external standard. The organic phase wasisolated and dried over anhydrous Na2SO4, and the conversion rate and enantioselectivity were determined by HPLC/GC as previouslydescribed [17,22]. |
42 % ee | With cytochrome P450 CYP199A4 S244D variant; NADH Enzymatic reaction; enantioselective reaction; | |
With hydroxy(phenyl)-λ3-iodanyl ((1S,4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl)methanesulfonate In acetone at -78℃; Overall yield = 73 percent; Optical yield = 4 percent ee; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With NaH-t-AmONa-Ni(OAc)2-bpy-KI In tetrahydrofuran; benzene at 63℃; for 2.5h; Yields of byproduct given; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With tert.-butyl lithium In tetrahydrofuran; hexane at -94℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With lithium hydroxide monohydrate; [N-((pyridin-2-ylmethyl)carbamothioyl)benzamide]; palladium diacetate In N,N-dimethyl-formamide at 130℃; for 10h; | General procedure for Heck reaction of aryl bromides with styrene: General procedure: The 25 mL RB flask was charged with aryl bromides (1 mmol), alkenes (2 mmol), LiOHH2O(2 mmol), and the catalyst (Pd(OAc)2/1a = 1:2, 0.001 mol % in 2 mL N,Ndimethylformamide).The reaction mixture was heated at 130 C for 10 h.Then the reaction mixture was cooled to room temperature, diluted with ethylacetate (20 mL), and washed with brine water. The combined organic phasewas dried over anhydrous Na2SO4. After removal of the solvent, the residuewas subjected to column chromatography on silica gel using ethyl acetate andhexane to afford the Heck product in high purity. |
83% | With dichloro{bis[1,1’,1’’-(phosphinetriyl)(II); tetrabutylammomium bromide; potassium carbonate In tetrahydrofuran; N,N-dimethyl-formamide at 100℃; for 24h; Schlenk technique; Glovebox; Inert atmosphere; Green chemistry; | |
With lithium acetate; tetrabutyl-ammonium chloride; lithium chloride In N,N-dimethyl-formamide at 115℃; Yield given; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With bis(µ-iodo)bis((-)-sparteine)dicopper(I); caesium carbonate In N,N-dimethyl-formamide at 125℃; for 9h; Inert atmosphere; | General procedure: The reaction vessel was charged with aryl halide (1 mmol), alkyne (1.1 mmol), Cs2CO3 (2 equiv) and the catalyst [Cu2I2(spa)2](1) (5 mol %) in N,N-dimethylformamide (3 mL). The reaction mixture was heated at 110-125 °C for the desired time (indicated in Table 2) and the progress of reaction was monitored by TLC. At the end of the reaction, the reaction mixture was cooled to room temperature and was diluted with EtOAc (20 mL), washed with 1 N aq HCl and water. The combined organic phase was dried over anhydrous Na2SO4. After removal of the solvent, the residue was subjected to column chromatography on silica gel using ethyl acetate and hexane to afford the desired product in high purity. |
75% | Stage #1: (4-bromophenyl)thioanisole; phenylacetylene With TPGS-750-M; triethylamine In water at 23 - 25℃; for 0.166667h; Inert atmosphere; Stage #2: With (2S,3S)-3-tert-butyl-4-(2,6-dimethoxyphenyl)-2-(2,4,6-triisopropylbenzyl)-2,3-dihydrobenzo[d][1,3]oxaphosphole; palladium diacetate In water; toluene at 45℃; for 24h; Inert atmosphere; | |
72% | With copper(l) iodide at 75℃; |
59% | With copper(l) iodide; ethanolamine; triphenylphosphine In water at 80℃; | |
58% | With sodium hydroxide In water at 60℃; for 1.5h; Green chemistry; | |
47% | With copper(l) iodide; triethylamine at 90℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With (R,R)-di-μ-oxo Ti(salen); urea hydrogen peroxide adduct In methanol at 0℃; for 24h; | |
89% | With tert.-butylhydroperoxide; iron(III) sulfate; (R,R)-N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamine In water for 2.3h; Reflux; optical yield given as %ee; enantioselective reaction; | |
82% | With dihydrogen peroxide In water at 25℃; stereoselective reaction; |
81% | Stage #1: (4-bromophenyl)thioanisole With bis(acetylacetonate)oxovanadium; C18H19I2NO2 In chloroform at 0℃; for 0.166667h; Stage #2: With dihydrogen peroxide In chloroform; water at 0℃; for 48h; optical yield given as %ee; enantioselective reaction; | |
81% | With tert.-butylhydroperoxide; (S)-[1,1']-binaphthalenyl-2,2'-diol; bismuth(III) oxide In water; ethyl acetate at 20℃; for 20h; Green chemistry; enantioselective reaction; | |
79% | Stage #1: (4-bromophenyl)thioanisole With iron(III) trifluoromethanesulfonate; C59H88N4O4 In tetrahydrofuran at 35℃; for 0.5h; Inert atmosphere; Stage #2: With dihydrogen peroxide In tetrahydrofuran; water at 25℃; for 4h; Inert atmosphere; enantioselective reaction; | |
77% | With titanium(IV) isopropylate; diethyl (2S,3S)-tartrate; Cumene hydroperoxide; water In dichloromethane at -20 - 20℃; Inert atmosphere; optical yield given as %ee; enantioselective reaction; | |
65% | With bis(acetylacetonate)oxovanadium; C17H19Br2NO2; dihydrogen peroxide In water; toluene at 0℃; for 8h; optical yield given as %ee; enantioselective reaction; | |
58% | With tert.-butylhydroperoxide In decane; water; toluene at 0 - 25℃; | |
35% | With naphthalene dioxygenase from intact cells of Pseudomonas putida NCIMB 8859; oxygen In water for 1h; | |
33% | With titanium(IV) isopropylate; tert.-butylhydroperoxide; (S)-[1,1']-binaphthalenyl-2,2'-diol In tetrachloromethane; water at 20℃; for 24h; enantioselective reaction; | |
31% | With Cumene hydroperoxide; titanium BINOL derivative In tetrachloromethane at 25℃; for 72h; | |
Multi-step reaction with 2 steps 1.1: aq. hydrogen peroxide; MnSO4*H2O / acetonitrile / 24 h / 20 °C 2.1: VO(acac)2; (R)-diiodo Shiff base ligand / CHCl3 / 1 h / 22 °C 2.2: aq. hydrogen peroxide / CHCl3 / 20 h / 0 °C | ||
98 % ee | With Acinetobacter baylyi ADP1; oxygen; NADH In ethanol at 30℃; Sealed tube; Enzymatic reaction; enantioselective reaction; | |
96 % ee | With D-Glucose; Rhodococcus aetherivorans BCP1 Baeyer-Villiger monooxygenase; NADPH In methanol at 30℃; for 12h; Enzymatic reaction; | Enzymatic synthesis of (R)- and (S)-aryl sulfoxides General procedure: A 10 mL reaction mixture contained 30-100 mM substrates dissolvedin methanol (5% v/v), 1.5 equivalent of glucose, 10 mg GDH, 0.2 mMNADP+ at 30 C and 180 rpm. Reactions were started by addition of 10g•L-1 dry cells of AmBVMO (15 U•g-1) or RaBVMO (23 U•g-1). Sampleswere withdrawn from the reaction mixture at different time intervals,and then extracted with equal volume of ethyl acetate supplementedwith 1 mM dodecane as an external standard. The organic phase wasisolated and dried over anhydrous Na2SO4, and the conversion rate and enantioselectivity were determined by HPLC/GC as previouslydescribed [17,22]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | Stage #1: (4-bromophenyl)thioanisole With n-butyllithium In tetrahydrofuran at -78℃; for 2h; Stage #2: With Trimethyl borate In tetrahydrofuran at -78 - 20℃; Stage #3: Further stages.; | |
56% | Stage #1: (4-bromophenyl)thioanisole With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.25h; Inert atmosphere; Stage #2: With Triisopropyl borate In tetrahydrofuran; hexane at -78 - 20℃; Inert atmosphere; | |
10% | Stage #1: (4-bromophenyl)thioanisole With n-butyllithium In tetrahydrofuran at -78 - 20℃; for 0.333333h; Stage #2: With Triisopropyl borate In tetrahydrofuran at -78 - 20℃; for 3h; | 62.1 Example 62; Preparation of 5-(4-fluoro-phenyl)-1-methyl-7-(4-methylsulfanyl-phenyl)-3-propyl-1H-pyrazolo[4,3-d]pyrimidine (E 62); Step 1: Preparation of 4-methylsulfanyl phenyl boronic acid To a cold (-78° C.) and stirring solution of 4-bromothioanisole (10) (3 grams, 14.8 mmol) in THF (15 mL) was added n-BuLi (10 mL) slowly under nitrogen atmosphere. The mixture was the allowed to reach the room temperature and stirring continued for 20 minutes. The mixture was then cooled to -78° C. A solution of triisopropyl borate (10 mL, 17.7 mmol) in THF (10 mL) was added to it slowly. The mixture was stirred for 1 hour at -78° C. and then 2 hours at room temperature. The mixture was acidified with cold 5% HCl, diluted with water (25 mL) and extracted with ethyl acetate. The organic layers were collected, combined, washed with brine solution (20 mL) followed by water (20 mL), dried over anhydrous Na2SO4 and concentrated. The residue thus obtained was purified by column chromatography using EtOAc-Hexane to afford the required aryl boronoc acid (11) (170 mg,). Yield: 10%; 1H NMR (200 MHz, CDCl3): δ 8.10 (d, J=7.9 Hz, 2H), 7.33 (d, J=7.9 Hz, 2H), 2.55 (s, 3H, SCH3), 1.56 (bs, D2O exchangeable, OH), 1.25 (s, exchangeable, OH). IR: vmax (KBr, cm-1): 3406, 1594. |
Stage #1: (4-bromophenyl)thioanisole With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.25h; Stage #2: In tetrahydrofuran; hexane at -78 - 20℃; Stage #3: With water In tetrahydrofuran; hexane Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With lithium hydroxide monohydrate In water at 80℃; for 6h; | General procedure for the Suzuki of aryl halides General procedure: A mixture of aryl halide (1.0 mmol), phenyl boronic acid (1.2 mmol), PS-tsu-Pd(II) complex (3) (0.005 mmol), LiOH.H2O (2 mmol), and water (2 mL) was stirred at 80 °C for 6 h. After completion of the reaction, the mixture was filtered to recover the catalyst. Then the experimental procedure was same as above. |
86% | With cetyltrimethylammonim bromide; potassium carbonate In water at 80℃; for 6h; Green chemistry; | |
86% | With cetyltrimethylammonim bromide; potassium carbonate In water at 80℃; for 6h; | General experimental procedure for Suzuki-Miyaura crosscouplingreaction General procedure: Catalyst 3 (10 mg, 0.004 mmol of Pd), arylboronic acid(0.75 mmol), aryl bromide (0.5 mmol), K2CO3 (138 mg, 1 mmol),cetyltrimethylammonium bromide (36 mg, 0.1 mmol), and water(3 mL) were added to a reaction vessel. The resulting mixturewas stirred at 80 C for 6 h, then cooled to room temperature andcatalyst was filtered, the crude residue was extracted with ethylacetate (3 10 mL). The combined organic layers were extractedwith water, saturated brine solution, and dried over anhydrousNa2SO4. The organic layers were evaporated under reduced pressureand the resulting crude product was purified by column chromatographyby using ethyl acetate/hexane (1:9) as eluent to givethe corresponding product. |
86% | With cetyltrimethylammonim bromide; potassium carbonate In water at 80℃; for 6h; | 2.3. General experimental procedure for Suzuki-Miyaura cross coupling reaction General procedure: Catalyst 3 (10 mg, 0.004 mmol of Pd), arylboronic acid(0.75 mmol), aryl bromide (0.5 mmol), K2CO3 (138 mg, 1 mmol),cetyltrimethylammonium bromide (36 mg, 0.1 mmol), and water(3 mL) were added to a reaction vessel. The resulting mixture was stirred at 80 °C for 6 h, then cooled to room temperature and catalyst was filtered, the crude residue was extracted with ethylacetate (3 10 mL). The combined organic layers were extracted with water, saturated brine solution, and dried over anhydrous Na2SO4. The organic layers were evaporated under reduced pressure and the resulting crude product was purified by column chromatography by using ethyl acetate/hexane (1:9) as eluent to give the corresponding product. |
80% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate In tetrahydrofuran; water at 85℃; for 2h; Inert atmosphere; | Synthetic Cross-Coupling Reactions; General Procedure General procedure: A microwave vial equipped with a stir bar was charged with 4- (1.1 mmol, 1.1 equiv.), [PdCl2(dppf)] (2), and K3PO4 (3 mmol, 3 equiv.). If the aryl halide was a solid, this was charged at this time also (1 mmol, 1 equiv.). The vial was sealed with a crimp cap and evacuated and backfilled three times with N2 or argon. The vial was then charged with anhyd, O2-free toluene or THF and the aryl halide if liquid (1 mmol, 1 equiv.). Degassed H2O was also added at this stage, if used. The reaction mixture was stirred for 2 h at 85 °C, then cooled to r.t., and quenched by piercing the septum. The reaction mixture was filtered through Celite, evaporated to dryness, and purified by column chromatography on silica gel. |
61% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In toluene for 12h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With niobium pentachloride; zinc powder In tetrahydrofuran; benzene at 23℃; for 3.5h; Inert atmosphere; | |
95% | With Aluminum Chloride; tetra-n-butyl-ammonium chloride; aluminium In 1,2-dichloro-ethane at 20℃; for 8h; Electrolysis; Inert atmosphere; Green chemistry; | |
94% | With indium powder; niobium pentachloride In tetrahydrofuran at 20℃; for 3h; |
94% | With [4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridine-κN1,κN1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-κN]phenyl-κC]iridium hexafluorophosphate; triphenylphosphine In dichloromethane at 20℃; for 24h; Inert atmosphere; Irradiation; | |
93% | With indium powder; titanium(IV) tetrachloride In tetrahydrofuran at 20℃; for 0.166667h; | |
93% | With hydrogen In 1,4-dioxane at 80℃; for 3h; chemoselective reaction; | |
93% | With hafnium tetrachloride; zinc powder In acetonitrile at 20℃; for 3h; 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] |
93% | With sodium iodide In ethanol at 20℃; for 3.33333h; 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. |
92% | With dichlorobis(N,N-dimethylformamide-κO)dioxomolybdenum; glycerol at 170℃; Green chemistry; chemoselective reaction; | |
91% | With indium powder; molybdenum pentachloride In tetrahydrofuran at 20℃; for 0.0833333h; | |
91% | With indium powder; tungsten hexachloride In tetrahydrofuran at 20℃; for 0.0833333h; | |
91% | With potassium borohydrate; hafnium tetrachloride In tetrahydrofuran for 12.3h; Inert atmosphere; Reflux; | |
91% | With niobium pentachloride; sodium iodide In acetonitrile at 20℃; for 0.0833333h; | |
91% | With 2,3-dimethyl-2,3-butane diol; MoO<SUB>2</SUB>Cl<SUB>2</SUB>(DMF)<SUB>2</SUB> at 90℃; for 4h; Neat (no solvent); chemoselective reaction; | |
91% | With MoO<SUB>2</SUB>Cl<SUB>2</SUB>(dmf)<SUB>2</SUB> In toluene at 140℃; for 0.166667h; Microwave irradiation; | |
91% | With hydrogen In neat (no solvent) at 120℃; for 24h; | |
91% | 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%). |
90% | With bis(η5-cyclopentadienyl) titanium dichloride; indium powder In tetrahydrofuran at 20℃; for 0.166667h; | |
90% | With indium powder; tantalum pentachloride In acetonitrile at 20℃; for 1.5h; 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. |
88% | With gallium(0); bis(η5-cyclopentadienyl) titanium dichloride In tetrahydrofuran at 20℃; for 0.5h; chemoselective reaction; | |
86% | With triethylsilane; tris(pentafluorophenyl)borate In neat (no solvent) at 100℃; for 8h; Glovebox; Inert atmosphere; | Reduction of Sulfoxides and Sulfones; General Procedure General procedure: In a glovebox, an oven-dried 1-mL screw-capped sealed tube with a magnetic stir bar was charged with B(C6F5)3 (10 mol%), Et3SiH (10 equiv), and the indicated oxidized sulfur compound (0.20 mmol). The tube was sealed properly and transferred to an oil bath preheated at100 °C. After 8 h, the reaction was cooled to r.t. and passed through asmall plug of silica gel using Et2O. The crude material was collected ina glass vial and subjected to GLC analysis to determine the conversion with respect to starting material. The ethereal solution was dried (Na2SO4) and filtered, and the solvent was removed under reduced pressure. The mixture was then subjected to high vacuum at 70 °C until the unreacted hydrosilane was removed from the system. If needed, the residue was purified further by flash column chromatography (silica gel, cyclohexane/Et2O 9:1) to afford the desired sulfides. |
85% | With indium powder; pivaloyl chloride In isopropanol at 20℃; for 1.5h; | |
81% | With tris[N,N-bis(trimethylsilyl)amide]yttrium; phenylsilane at 130℃; for 24h; Inert atmosphere; | 6 Example 6 The preparation of 4-bromothioanisole, the structural formula is as follows: Under nitrogen protection, the raw materials 4-bromophenylmethyl sulfoxide (0.3 mmol) and phenylsilane (0.9 mmol) were added, the catalyst Y[N(SiMe3)2]3 (0.03 mmol) was added, and the reaction was carried out at 130 ° C for 24 h, The product isolation yield was 81%. |
75% | Stage #1: 1-bromo-4-(methylsulfinyl)benzene With oxalyl dichloride In tetrahydrofuran at -78℃; for 1h; Stage #2: With isopropanol In tetrahydrofuran at -78℃; for 1h; Stage #3: With triethylamine In tetrahydrofuran at -78 - 20℃; Further stages.; | |
75% | Stage #1: 1-bromo-4-(methylsulfinyl)benzene With oxalyl dichloride In tetrahydrofuran at -78℃; for 1h; Cooling with acetone-dry ice; Stage #2: With isopropanol In tetrahydrofuran for 1h; Cooling with acetone-dry ice; Stage #3: With triethylamine In tetrahydrofuran for 0.05h; Cooling with acetone-dry ice; | To a stirred and cooled (-78 °C) solution of the sulfoxide [I] (497 mg, 2.27 mmol) in THF (4 mL) under a nitrogen atmosphere was added oxalyl chloride (0.26 mL, 2.95 mmol). After 1 h, 2-propanol (0.35 mL, 4.54 mmol) was added dropwise. The reaction mixture was stirred for a further 1 h, and then Et3N (1.58 mL, 11.35 mmol) was added. After 3 min. , the mixture was removed from the solid C02/acetone bath and allowed to warm to room temperature, and then partitioned between CHCl3/brine. The aqueous layer was extracted with CHCl3 (2x) and the combined organic extracts dried (MgSO4), filtered and concentrated in vacuo. Analysis of the crude product revealed a 87 : 1 mixture of the sulfide and sulfoxide, respectively (based on integration of signals at δ 2.46 and 2. 68 in the 400 MHz 1H NMR spectrum). Purification by silica gel chromatography [hexanes-IPA (100 : 1) ] afforded sulfide II (343 mg, 75 %). |
75% | With bis(1,5-cyclooctadiene)iridium(I) tetrafluoroborate; dimethyl diazomalonate In 1,2-dichloro-ethane at 80℃; for 12h; Schlenk technique; Inert atmosphere; | 3. General Procedure for preparing common Sulfides General procedure: Under nitrogen atmosphere, sulfoxide (0.5 mmol), Dimethyl Diazomalonate (120 mg, 0.75 mmol), Ir(COD)2BF4 (0.0025mmol, 1.23mg ), dry DCE (5 mL) were put into an over-dried Schlenk tube. The mixture was heated at 80oC for 12 h, then cooled down and concentrated under vacuum. The residue was purified by flash column chromatography to give the desired products |
73% | With tris(pentafluorophenyl)borate; phenylsilane In toluene at 60℃; for 8h; Inert atmosphere; Schlenk technique; Green chemistry; | |
59% | With hydrogenchloride; N-Bromosuccinimide In 1,4-dioxane at 120℃; for 10h; Schlenk technique; Sealed tube; | 2 General procedure for synthesis of compounds 2 General procedure: Under an air atmosphere,a 10 mL of Schlenk tube equipped with a stir bar was charged with sulfoxide(0.2 mmol), NBS (0.2 equiv), HCl (2.0 equiv, 12 M) and 1,4-dioxane(2.0 mL). The tube was sealed with a Teflon lined cap. The reaction mixturewas stirred at 120 °C for 10 h in oil bath. After the completion ofthe reaction, saturated NaOH (2 mL) was added to the mixture, and extractedwith ethyl acetate (4 mL × 3). The combined organic extracts were dried over anhydrous Na2SO4. Subsequently, the solvent was filtered and evaporated under reduced pressure, and theresidue was purified by flash column chromatography on silica gel withpetroleum as the eluent to give the desired products. |
With oxalyl dichloride; triethylamine; isopropanol In dichloromethane at -78℃; | ||
> 99 %Chromat. | With isopropanol In toluene at 110℃; for 2h; Inert atmosphere; Green chemistry; chemoselective reaction; | 4) Typical reaction procedure General procedure: RuNP/HAP (0.05 g: Ru 0.025 mmol) and iso-propanol (0.5 mL) were added to a solution of diphenylsulfoxide in toluene (0.1 M, 0.5 mmol). The mixture was stirred at 110 oC for 1 h. The yields of the products were determined by GC using naphthalene as an internal standard. |
98 %Chromat. | With hydrogen In decane at 100℃; for 2h; Schlenk technique; Sealed tube; | |
100 %Chromat. | With hydrogen In methanol at 50℃; for 26h; Autoclave; | |
97 %Chromat. | With hydrogen In toluene at 160℃; for 12h; Autoclave; Molecular sieve; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With potassium carbonate In 1,4-dioxane; water monomer for 2h; Heating; | |
93% | With dichloro[ 1,1’-bis(di-tert-butylphosphino)ferrocene]palladium (II); potassium carbonate In water monomer; acetonitrile at 60℃; Inert atmosphere; Sealed vessel; | 4.6. Typical preparative procedure Typical preparative procedures were performed on 10.0 mmol scale using a Mettler-Toledo FlexiWeigh 30 automated solid handling unit to pre-weigh the aryl halide (10.0 mmol, 1.0 equiv), aryl boronic acid (12.0 mmol, 1.2 equiv) and Pd-118 (65.2 mg, 0.1 mmol, 1.0 mol %). Acetonitrile (10.0 mL) was added, followed by K2CO3 added as a stock aqueous solution (10.0 mL water containing 2.07 g, 15.0 mmol, 1.5 equiv). NB. No internal standard was added for preparative reactions. Reaction mixtures were sealed under a N2 atmosphere and heated to 60 °C with magnetic stirring. HPLC analysis showed that reactions using aryl bromides were complete within 1 h but that aryl chlorides typically required 24 h.After reaction mixtures had cooled to room temperature, stirring was stopped and the phases were allowed to separate. The lower aqueous phase was removed and discarded (cutting away any interfacial catalyst residues if present) and the acetonitrile phase concentrated to dryness to give typically a light to dark brown solid or dark-coloured gum. Solids were triturated with methanol (20 mL) for 1-2 h, then isolated by filtration, washed once or twice with methanol (4 mL each wash) and dried under vacuum. Oils were purified by flash silica gel chromatography as noted below. All isolated compounds gave 1H NMR data in agreement with published values. Literature data is given for mp values for comparison. |
92% | With {2,6-bis[(di-1-piperidinylphosphino)amino]phenyl}palladium(II) chloride; potassium carbonate In 1,4-dioxane; water monomer; butan-1-ol at 100℃; for 3h; |
92% | With lithium hydroxyde monohydrate; C23H30N2O3Pd In methanol; water monomer; N,N-dimethyl-formamide at 50℃; for 24h; Green chemistry; | |
91% | With tripotassium phosphate tribasic; dichloro{bis[1-(dicyclohexylphosphanyl)(II) In toluene at 80℃; for 0.166667h; Air; | |
90% | With lithium hydroxyde monohydrate In water monomer at 80℃; for 6h; | General procedure for the Suzuki of aryl halides General procedure: A mixture of aryl halide (1.0 mmol), phenyl boronic acid (1.2 mmol), PS-tsu-Pd(II) complex (3) (0.005 mmol), LiOH.H2O (2 mmol), and water (2 mL) was stirred at 80 °C for 6 h. After completion of the reaction, the mixture was filtered to recover the catalyst. Then the experimental procedure was same as above. |
90% | With [1,3-bis(2,6-di-3-pentylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(II) dichloride; potassium hydroxide In 1,4-dioxane at 65℃; for 4h; Inert atmosphere; Schlenk technique; | 2 Step 2 A 25-mL round bottom flask equipped with a stir-bar was charged with (4- bromophenyl)(methyl)sulfane (21, 460 mg, 2.46 mmol, 1 equiv.), Pd-PEPPSI-IPent (39 mg, 2 mol%), phenylboronic acid (22, 600 mg, 4.92 mmol, 2.0 equiv.), and potassium hydroxide (830 mg, 14.8 mmol, 6.0 equiv.).The flask was sealed with a rubber septum and purged with argon (3X). Dioxane (10.0 mL) was then added via syringe and the reaction was stirred at 65 °C for 4 h. The reaction mixture was diluted with diethyl ether (75 mL) and washed with 0.1N HCl (2 X 25 mL), water (2x 25 mL) and brine (25 mL). Dried over anhydrous MgSO4 and filtered. The contents were concentrated under reduced pressure and the crude was passed through a pad of silica washing with 50% ethyl acetate/hexanes to give [1,1'-biphenyl]-4-yl(methyl)sulfane 23 as an off-white solid (407 mg, 90%).1H-NMR (400 MHz, CDCl3) ^: 7.55-7.45 (m, 4H), 7.44 (t, 2H), 7.35 (m, 3H), 3.71 (s, 3H). |
88% | With [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(II) dichloride; potassium carbonate at 110℃; for 0.166667h; Microwave irradiation; Neat (no solvent); | |
88% | With N-hexadecyl-N,N,N-trimethylammonium bromide; potassium carbonate In water monomer at 80℃; for 6h; Green chemistry; | |
88% | With N-hexadecyl-N,N,N-trimethylammonium bromide; potassium carbonate In water monomer at 80℃; for 6h; | General experimental procedure for Suzuki-Miyaura crosscouplingreaction General procedure: Catalyst 3 (10 mg, 0.004 mmol of Pd), arylboronic acid(0.75 mmol), aryl bromide (0.5 mmol), K2CO3 (138 mg, 1 mmol),cetyltrimethylammonium bromide (36 mg, 0.1 mmol), and water(3 mL) were added to a reaction vessel. The resulting mixturewas stirred at 80 C for 6 h, then cooled to room temperature andcatalyst was filtered, the crude residue was extracted with ethylacetate (3 10 mL). The combined organic layers were extractedwith water, saturated brine solution, and dried over anhydrousNa2SO4. The organic layers were evaporated under reduced pressureand the resulting crude product was purified by column chromatographyby using ethyl acetate/hexane (1:9) as eluent to givethe corresponding product. |
88% | With N-hexadecyl-N,N,N-trimethylammonium bromide; potassium carbonate In water monomer at 80℃; for 6h; | 2.3. General experimental procedure for Suzuki-Miyaura cross coupling reaction General procedure: Catalyst 3 (10 mg, 0.004 mmol of Pd), arylboronic acid(0.75 mmol), aryl bromide (0.5 mmol), K2CO3 (138 mg, 1 mmol),cetyltrimethylammonium bromide (36 mg, 0.1 mmol), and water(3 mL) were added to a reaction vessel. The resulting mixture was stirred at 80 °C for 6 h, then cooled to room temperature and catalyst was filtered, the crude residue was extracted with ethylacetate (3 10 mL). The combined organic layers were extracted with water, saturated brine solution, and dried over anhydrous Na2SO4. The organic layers were evaporated under reduced pressure and the resulting crude product was purified by column chromatography by using ethyl acetate/hexane (1:9) as eluent to give the corresponding product. |
88% | With tetrakis-(triphenylphosphine)-palladium; anhydrous sodium carbonate In methanol; water monomer; toluene at 100℃; for 24h; | |
84.3% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II) dichloromethane adduct; di-i-propyl amine In water monomer; isopropanol at 120℃; for 0.5h; Inert atmosphere; Irradiation; | |
83% | With tripotassium phosphate tribasic In 1,4-dioxane at 80℃; for 12h; | |
83% | With tripotassium phosphate tribasic at 80℃; for 2h; | |
82% | With (1-(2,6-diisopropylphenyl)-2,3-dihydro-1H-imidazol-2-yl)(methyl(λ1-oxidaneyl)diphenyl-λ5-phosphaneyl)palladium(II) chloride; Cs2CO3 In methanol; dichloromethane; toluene at 100℃; Glovebox; | |
80% | With dicyclohexyl({2’,6’-dimethoxy-[1,1‘-biphenyl]-2-yl})phosphane; tripotassium phosphate tribasic; palladium diacetate In toluene at 110℃; for 24h; | N-(Biphenyl-4-yl)pyridin-2-ylamine (3ha) To a Schlenk tube were added 4-bromothioanisole (7a) (304 mg, 1.63mmol), phenylboronic acid (270 mg, 2.21 mmol), Pd(OAc)2 (11 mg,0.049 mmol), SPhos (19 mg, 0.046 mmol), and K3PO4 (424 mg, 3.12mmol) under an argon atmosphere. Toluene (4.5 mL) was then addedand the mixture heated at 110 °C for 24 h. After complete conversion,the reaction mixture was cooled to room temperature. Chromatographicpurification afforded 4-methylsulfanylbiphenyl (260 mg, 1.30mmol, 80% yield). 2-Aminopyridine (2a) (28.2 mg, 0.30 mmol), 4-methylsulfanylbiphenyl(50 mg, 0.25 mmol), SingaCycle-A1 (12.5 mg, 0.019 mmol), andKHMDS (150 mg, 0.75 mmol) were placed in a Schlenk tube under anitrogen atmosphere and the resulting mixture was stirred at 100 °Cfor 24 h. The reaction mixture was poured into water and extractedwith ethyl acetate (3 × 30 mL). The combined organic layer was driedover sodium sulfate and the solvent was removed under reducedpressure. The obtained crude product was purified by column chromatographyusing 25% ethyl acetate in hexane as the eluent to yield 3ha. |
80% | With tetrakis-(triphenylphosphine)-palladium; anhydrous sodium carbonate In methanol; water monomer; toluene at 100℃; for 24h; | 8. Preparation of Substrates 8.2 Preparation of 3m. A 100 mL round-bottom flask was charged with Pd(PPh3)4 (346.7 mg, 0.3 mmol, 0.06 equiv.), Na2CO3 (794.9mg, 7.0 mmol, 1.4 equiv.), phenylboronic acid (853.5 mg, 7.0 mmol, 1.4 equiv.) and toluene (15 mL). (4-Bromophenyl)(methyl)sulfane (1.0 g, 5.0 mmol, 1.0 equiv.) in the mixture solvent of MeOH (3 mL) and H2O(17 mL) were then added. The reaction mixture was stirred at 100 °C for 24 hours. The reaction mixture wascooled to room temperature and concentrated. The residue was diluted with CH2Cl2 (20 mL) and water (10mL). The layers were separated and the aqueous phase was extracted with CH2Cl2 (5 mL × 3). The combinedorganic layers were dried over Na2SO4 and concentrated in vacuo. The crude product was purified by silicagelcolumn chromatography (hexanes, Rf = 0.4) to give the product 3m (800 mg, 80% yield) as a white solid.M.P.: 104 - 107 . 1H NMR (400 MHz, Chloroform-d) δ 7.60 - 7.57 (m, 2H), 7.55 - 7.52 (m, 2H), 7.47 -7.42 (m, 2H), 7.37 - 7.32 (m, 3H), 2.53 (s, 3H). 13C NMR (101 MHz, Chloroform-d) δ 140.7, 138.2, 137.7,128.9, 127.6, 127.3, 127.1, 127.0, 16.0. |
60% | With tripotassium phosphate tribasic In water monomer at 60℃; for 3.9h; | |
98 %Chromat. | With tris(dibenzylideneacetone)dipalladium(0) chloroform complex; sodium hydroxide; C78H99N6P(6+)*6Br(1-) In methanol; water monomer for 22h; Reflux; Inert atmosphere; | |
With diacetato(κ2-N,N'-9,10,11,15-tetrahydro-(11S,15S)-(N,N-dimethyl-ethylenediamine)-9,10-pyrrolanthracene)palladium; anhydrous sodium carbonate In water monomer; toluene at 65℃; for 6h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With copper(l) iodide; dimethylaminoacetic acid; potassium carbonate In N,N-dimethyl-formamide at 120℃; for 24h; Inert atmosphere; | General procedure for the synthesis of N-aryloxazolidinones. General procedure: A Schlenk tube was charged with aryl bromide(1 mmol), oxazolidone(1.2 mmol), N,N-dimethylglycine(10.3mg, 0.1 mmol), recrystallized CuI(9.5mg, 0.05 mmol) and K2CO3(276mg, 2 mmol). The tube was evacuated and backfilled with argon(3 times) before dry DMF(0.5 ml) was added. The reaction mixture was stirred at 120 °C until the corresponding aryl bromidewas completely consumed as monitored by TLC. The reaction mixture was extracted with ethyl acetate. The organic layer was washed with H2O and brine, and dried by Na2SO4. Removal of solvent in vacuo and purified by column chromatography on silica gel to provide the desired product. |
86% | With copper(l) iodide; (S,S)-1,2-diaminocyclohexane; potassium carbonate In 1,4-dioxane for 15h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With potassium carbonate In acetonitrile for 12h; Reflux; | |
95% | With triethylamine In acetonitrile at 20℃; for 12h; | |
84% | With potassium carbonate In acetone for 12h; Reflux; | 8. Preparation of Substrates General procedure: 8.1 Generally Procedure for the Preparation of 3c, 3l, 3o, 3f, 3s.Thiophenol (5.0 mmol, 1.0 equiv.) was dissolved in acetone (30 mL), and then potassium carbonate (1.4 g,10.0 mmol, 2.0 equiv.) was added. After iodomethane (2.1g, 15.0 mmol, 3.0 equiv.) was added dropwise, themixture was heated to reflux for 12 h. Then, the reaction mixture was cooled to room temperature, filteredthrough celite and the solvent removed under reduced pressure. The residue was diluted with EtOAc (15 mL),washed with brine (10 mL), dried with Na2SO4 and concentrated in vacuo. The crude product was purified byflash column chromatography to give the correspounding product. |
70% | With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 12h; | 1013.1 Step-1: Synthesis of (4-bromophenyl)(methyl)sulfane To a stirred solution of 4-bromobenzenethiol (1.0g ,5.31 mmol) in DMF (10 mL) was added K2CO3 (1.46 g,10.63 mmol) followed by MeI (1.13 g,7.97mmol) at RT and allowed to stir for 12h at same temperature. Reaction was monitored by TLC. On completion reaction was diluted with water , extracted with EtOAc .The organic layer was washed with brine, dried over sodium sulphate, concentrated under reduced pressure obtained (4- bromophenyl)(methyl)sulfane (0.7 g,70%) as light brown solid. MS: 203.2[M++1] |
44% | With sodium hydride In tetrahydrofuran at 20℃; for 1h; Inert atmosphere; Schlenk technique; | 1 Step 1 A 25-mL round bottom flask equipped with a stir-bar was charged with sodium hydride (141 mg, 5.88 mmol, 1.1 equiv.). The flask was sealed with a rubber septum and purged with argon (3X).4-Bromobenzenethiol (20, 1.00 g, 5.34 mmol, 1.0 equiv.) in THF (5 mL) was added dropwise via a syringe, followed by MeI (289 mL, 5.88 mmol, 1.10 equiv.). Stirred at room temperature for 1h. Quenched with the addition water and diluted with diethyl ether, washed with water (2x 25 mL) and brine (25 mL). Dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The crude was purified by silica gel column (0457) chromatography to give (4-bromophenyl)(methyl)sulfane 21 as an off-white solid (480 mg, 44%).1H-NMR (300 MHz, CDCl3) ^: 7.39 (d, 2H), 7.11 (d, 2H), 2.45 (s, 3H). |
3.4 g | Stage #1: para-bromobenzenethiol With sodium hydride In tetrahydrofuran at 0℃; for 0.0833333h; Stage #2: iodomethane In tetrahydrofuran at 20℃; for 0.25h; | |
Stage #1: para-bromobenzenethiol With sodium hydroxide In ethanol for 0.5h; Stage #2: iodomethane In ethanol at 20℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40.7% | Stage #1: (4-bromophenyl)thioanisole With n-butyllithium In diethyl ether; hexane at 0℃; for 1h; Stage #2: With phosphorus trichloride In diethyl ether; hexane at 0℃; Stage #3: With hydrogenchloride In diethyl ether; hexane at 20℃; | |
30% | With n-butyllithium; phosphorus trichloride In tetrahydrofuran at 20℃; for 52h; | 1.a a) Preparation OF TRIS (4-THIOANISYL) phosphine A COOLED SOTUFION OF 4-OROMOTHIOANISOLE (1 90. 8G ; 0. 94 MOL) AND anhydrous tetrahydrofuran (750 ML) under nitrogen was treated dropwise with 2.5 M n-Butyllithium (375 mi ; 0. 94 mol) in tetrahydrofuran. The cooled mixture was then treated dropwise with A solution of phosphorus trichloride (39. 0g ; 0. 28 mol) and anhydrous tetrahydrofuran (100 ML). The resulting mixture was allowed to warm to room temperature and left to stir for 52 hours. The reaction was quenched with water (500 ML) and extracted with diethyl ether. The combined extracts were dried with magnesium sulphate, filtered and evaporated to dryness to give a pasty yellow solid. Trituration with ethanol yielded tris (4-thioanisyl) phosphine (V) as a white solid (33. 8g ; 30% yield). |
Stage #1: (4-bromophenyl)thioanisole With magnesium; ethylene dibromide In tetrahydrofuran for 2.5h; Inert atmosphere; Heating; Stage #2: With phosphorus trichloride In tetrahydrofuran at -78 - 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With 1,10-Phenanthroline; caesium carbonate; 1,5-diphenyl-1,4-pentadiene-3-one In xylene at 110℃; | |
88% | With potassium carbonate; copper(II) sulfate at 205℃; for 10h; | 1-(4-Methylthiophenyl)-1H-imidazole was synthetized according to a modified literature procedure. Imidazole (3.24g, 47.57mmol), 4-bromothioanisole (4.83g, 23.78mmol), K2CO3 (3.29g, 23.78mmol) and a catalytic amount of CuSO4 were stirred in a closed pressure tube at 205°C for 10h. After cooling to room temperature, the crude product was extracted with MeOH, filtered and evaporated to dryness. The resulting residue was purified by column chromatography on silica gel with a mixture of CH2Cl2 and methanol (90:10) as eluent to give 1-(4-methylthiophenyl)-1H-imidazole as a yellow solid (3.99g, 88% yield). 1H NMR (300MHz, CDCl3) δ 7.93 (s, 1H), 7.40-7.31 (m, 4H), 7.28 (s, 1H), 7.24 (s, 1H), 2.54 (s, 3H) [25]. |
86% | With copper(I) oxide; sodium t-butanolate In 1-methyl-pyrrolidin-2-one at 120℃; for 15h; Microwave irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | Stage #1: 4-acetylmorpholine With sec.-butyllithium In tetrahydrofuran; cyclohexane at -78℃; for 1h; Stage #2: With zinc(II) chloride In tetrahydrofuran; cyclohexane at 20℃; for 0.166667h; Stage #3: (4-bromophenyl)thioanisole With monophosphine 1,2,3,4,5-pentaphenyl-1'-(di-tert-butylphosphino)ferrocene; bis(dibenzylideneacetone)-palladium(0) In tetrahydrofuran; cyclohexane at 20℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | In acetonitrile at 20℃; for 5h; | |
70% | With iodine In dichloromethane at 20℃; for 24h; Inert atmosphere; | 4.2. General Procedure for Imination of Sulfides 1 with Imino-phenyl-l3-iodane 2 in the Presence of I2 General procedure: Imino-3-iodane 2 (0.12-0.24 mmol) was added at room temperature to a stirred mixture of sulfide1 (0.10-0.20 mmol) and I2 (0.002-0.004 mmol) in dichloromethane (1.0-2.0 mL). The reaction wasstirred at room temperature for 24 h. After the reaction, 5% aqueous Na2S2O3 (2.5-5.0 mL) was addedto the mixture and the solution was extracted with ethyl acetate. The organic layer was dried overanhydrous Na2SO4 and concentrated under reduced pressure. The residue was separated by columnchromatography using the Hexane-EtOAc (1:1 to 0:100) to afford the pure product 3. |
99 %Spectr. | With C45H55BCuN6PS3 In acetonitrile at 20℃; for 0.5h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96.39% | With [bis(acetoxy)iodo]benzene; ammonium acetate In ethanol at 20℃; for 2h; | 28.1 Step 1: Synthesis of Compound 28-1 At room temperature, compound 1-bromo-4-methylsulfonamidobenzene (1.8 g) was dissolved in EtOH (90 mL), PhI(OAc) 2 (8.56 g) and NH 4 OAc (10.92 g) were added at room temperature, and stirred at room temperature for 2 Hour. Return to room temperature, spin dry the solvent, concentrate, and the concentrate is purified by silica gel column to obtain the product 28-1 (2.0 g, 96.39% yield) as a white solid. |
89% | With [bis(acetoxy)iodo]benzene; ammonium acetate In ethanol at 20℃; for 2h; | 6 Embodiment 6 The thioether (203 mg, 1.0 µM), iodobenzene diacetate (966 mg, 3.0 µM), ammonium acetate (308 mg, 4.0 µM) containing ethanol is added 10 ml bottle of the reaction, the reaction at room temperature for two hours. After the reaction is finished to remove the solvent, column chromatography treatment, to obtain the product of 208 mg, yield 89%. |
85% | With diacetoxyiodo-3,4,5-trifluorobenzene; lithium hydroxide monohydrate; ammonium bicarbonate at 25℃; for 16h; Green chemistry; |
85% | With para-iodoanisole; ammonium acetate; tetra-n-butylammonium acetate; tetra-n-butylammonium hexafluoridophosphate In methanol at 25℃; Electrolysis; | |
Multi-step reaction with 2 steps 1: H2O2; acetic acid / H2O / -5 - 20 °C 2: 56 percent / NaN3; H2SO4 / CHCl3 / 0 - 20 °C | ||
Multi-step reaction with 4 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 16 h / 0 °C 2: tetrahydrofuran / 2 h / Reflux 3: sodium (meta)periodate; ruthenium(III) chloride tetrahydrate / acetonitrile; lithium hydroxide monohydrate / 1 h / 20 °C 4: sulfuric acid / lithium hydroxide monohydrate / 2 h / 110 °C | ||
Multi-step reaction with 2 steps 1.1: dihydrogen peroxide; glacial acetic acid / lithium hydroxide monohydrate / 0 - 20 °C 2.1: Caswell No. 744A / chloroform / 20 °C 2.2: 0 - 20 °C | ||
Multi-step reaction with 3 steps 1.1: potassium-t-butoxide; NBS / methanol / 2 h / 20 °C / Inert atmosphere 2.1: 3-chloro-benzenecarboperoxoic acid; potassium carbonate / ethanol / 20 °C / Cooling with ice 3.1: trifluoroacetic anhydride / dichloromethane / 20 °C / Cooling with ice 3.2: 36 h / 20 °C | ||
Multi-step reaction with 3 steps 1.1: potassium-t-butoxide; NBS / methanol / 2 h / 20 °C / Inert atmosphere 2.1: 3-chloro-benzenecarboperoxoic acid; potassium carbonate / ethanol / 20 °C 3.1: trifluoroacetic anhydride / dichloromethane / 1.5 h / 20 °C 3.2: 36 h / 20 °C | ||
Multi-step reaction with 2 steps 1: copper (II) bromide; tert.-butylhydroperoxide / acetonitrile; lithium hydroxide monohydrate / Reflux 2: Caswell No. 744A; sulfuric acid / chloroform / 12 h / 0 - 45 °C | ||
Multi-step reaction with 2 steps 1: glacial acetic acid; dihydrogen peroxide / lithium hydroxide monohydrate / 12 h / 0 - 20 °C 2: Caswell No. 744A / chloroform / 12 h / 0 °C | ||
Multi-step reaction with 2 steps 1: tert.-butylhydroperoxide; copper (II) bromide / lithium hydroxide monohydrate; acetonitrile / Inert atmosphere; Reflux 2: Caswell No. 744A; sulfuric acid / chloroform / 12 h / 0 - 45 °C / Inert atmosphere | ||
With [bis(acetoxy)iodo]benzene; ammonium bicarbonate In methanol at 20℃; Inert atmosphere; | ||
Multi-step reaction with 3 steps 1.1: NBS; potassium-t-butoxide / methanol / 20 °C / Inert atmosphere 2.1: ruthenium (III) chloride / acetonitrile; dichloromethane / 0.08 h / 20 °C / Inert atmosphere 2.2: 20 °C / Inert atmosphere 3.1: sulfuric acid / 2 h / Reflux | ||
With ammonium bicarbonate; iodobenzene diacetate In methanol at 20℃; for 0.166667h; | 3.2.1. General Procedure A for the Synthesis of Substrates 1a-1w General procedure: To a stirred solution of sulfide (1 mmol) in MeOH (10 mL) was added (NH4)2CO3 (1.5 equiv.).Subsequently, PhI(OAc)2 (2.3 equiv.) was added, and the solution was stirred at rt for 10 min.The solvent was removed under reduced pressure, and the crude product was purified by flash columnchromatography eluted with dichloromethane (DCM)/MeOH from 30:1 to 10:1 to give the desiredproduct 1. Compounds 1e, 1f, 1q, R-1a, and S-1a were purchased from commercial sources and usedwithout further purification. Compounds 1a-1c, 1g-1i, 1l-1p, 1r-1w are known compounds. | |
With [bis(acetoxy)iodo]benzene; ammonium bicarbonate In methanol for 1h; Sealed tube; | ||
With [bis(acetoxy)iodo]benzene; ammonium carbamate In methanol at 20℃; for 0.5h; | ||
With [bis(acetoxy)iodo]benzene; ammonium bicarbonate In methanol at 20℃; for 0.75h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | A MIXTURE OF 4- (3-CYCLOPENTYLOXY-4-METHOXY-PHENYL)-PYRROLIDIN-2-ONE (276 mg, 1 mmol), 1-bromo-3-methylsulfanylbenzene (1.4 mmol), K3PO4 (1.5 mmol), DMF (3 mL), dioxane (3 mL) and 1, 2-TRANS-CYCLOHEXANEDIAMINE (25 UL) was stirred under N2 for 5 min before Cul (35 mg) was added. The reaction mixture was heated at 110 C for 20 h under N2 with stirring, then cooled down to r. t. The mixture was diluted with EtOAc, washed with saturated NH4C1 (3X10 mL) and dried over NA2S04. CONCENTRATION and chromatography of the residue on silica gel gave 282 mg of pure product. Yield: 71%. 6.1.a 4-(3-cyclopentyloxy-4-methoxyphenyl)-1-(4-methylsulfanylphenyl)- PYRROLIDIN-2-ONE 'H NMR (CDC13) : No. 7.33-7. 30 (m, 2H), 7.21-7. 20 (m, 2H), 6.88-6. 86 (m, 3H), 4.81-4. 78 (m, 1H), 3.87-3. 85 (m, 4H), 3.78-3. 70 (m, 1H), 3.01-2. 90 (m, 2H), 2.75 (dd, 1H, J = 9.1, 18.4 Hz), 1. 95-1.82 (m, 6H), 1.63-1. 60 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With tris-(dibenzylideneacetone)dipalladium(0); potassium <i>tert</i>-butylate; DavePhos In 1,4-dioxane at 120℃; for 0.25h; Microwave irradiation; | 1 Step 1: tert-butyl 4-(4-(methylthio)phenyl)piperazine-1-carboxylate To a degassed stirred solution of (4-bromophenyl)(methyl)sulfane (5.0 g, 24.6 mmol), 1-Boc-piperazine (4.6 g, 24.6 mmol), Davephos (2.63 g, 6.66 mmol, Combi-blocks) and KOfBu (4.7 g, 49.0 mmol) in 1, 4 dioxane (10 ml_), Pd(dba)3 (0.45 g, 0.4 mmol) was added at RT. The reaction mixture was heated under microwave irradiation at 120 °C for 15 min. Completion of the reaction was monitored by TLC, the reaction mixture was then evaporated at 50 °C under reduced pressure. To the resulting crude mixture, water (10 ml_) was added and the aqueous layer was extracted with EtOAc (2 x 50 ml_). The combined organic layer was dried over anhydrous Na2S04 and concentrated under vacuum. The resulting crude material was purified by flash chromatography (Biotage Isolera, eluent: 50% EtOAc in pet-ether) to afford the tittle compound. Yield: 88% (6.0 g, off white solid). 1H NMR (400 MHz, DMSO-d6): d 7.25-7.23 (m, 2H), 6.96- 6.93 (m, 2H), 3.58-3.57 (m, 4H), 3.12-3.09 (m, 4H), 2.42 (s, 3H), 1.50 (s, 9H). LCMS: (Method A) 309.2 (M+H), Rt. 4.3 min, 98.7% (Max). |
79% | With sodium t-butanolate In 1,4-dioxane at 100℃; for 0.1h; Microwave; | 39 Under an inert atmosphere of argon, sodium ferf-butoxide (200 mg; 2.08 mmol) was added in one portion to a room temperature stirring solution of Λ/-Boc-piperazine (199 mg; 1.07 mmol), 1-bromo-4-(methylthio)benzene (217 mg; 1.07 mmol), 2- dicyclohexylphosphino-2'-(N,N-dimethylamino)biphenyl (113 mg; 0.29 mmol), and Pd2(dba)2 (57 mg; 62 μmol) in degassed 1 ,4-dioxan (5 ml_). The mixture was sonicated for 1 minute, and stirred under microwave conditions in a sealed tube at 1000C for 5 minutes. The crude mixture was partitioned between ethyl acetate (40 mL) and water (40 ml_), and the separated aqueous extracted with ethyl acetate (40 mL). The combined organic phase was dried (MgSO4), and concentrated in vacuo. The resulting brown oil was purified by column chromatography, giving the title compound 4-[4-(methylthio)phenyl]piperazine-1- carboxylic acid-terf-butylester as a yellow solid (259 mg; 79%). LC/MS (Ammonium bicarbonate ES+) Found 209 (M-Boc+H). |
79% | With bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; DavePhos In 1,4-dioxane at 20 - 100℃; for 0.1h; Sonographic reaction; | 68 Under an inert atmosphere of argon, sodium tert-butoxide (200 mg; 2.08 mmol) was added in one portion to a room temperature stirring solution of /V-Boc-piperazine (199 mg; 1.07 mmol), 1-bromo-4-(methylthio)benzene (217 mg; 1.07 mmol), 2- dicyclohexylphosphino-2'-(Λ/,Λ/-dimethylamino)biphenyl (113 mg; 0.29 mmol), and Pd2(dba)2 (57 mg; 62 μmol) in degassed 1 ,4-dioxan (5 mL). The mixture was sonicated for 1 minute, and stirred under microwave conditions in a sealed tube at 1000C for 5 minutes. The crude mixture was partitioned between ethyl acetate (40 mL) and water (40 mL), and the separated aqueous extracted with ethyl acetate (40 mL). The combined organic phase was dried (MgSO4), and concentrated in vacuo. The resulting brown oil was purified by column chromatography, giving the title compound 4-[4-(methylthio)pheny.]piperazine-1- carboxylic acid-fert-butylester as a yellow solid (259 mg; 79%). LC/MS (Ammonium bicarbonate ES+) Found 209 (M-Boc+H, TR 3.47 min). |
79% | With sodium t-butanolate In 1,4-dioxane at 100℃; for 0.1h; Sonographic reaction; Microwave irradiation; | 39 Under an inert atmosphere of argon, sodium fe/f-butoxide (200 mg; 2.08 mmol) was added in one portion to a room temperature stirring solution of Λ/-Boc-piperazine (199 mg; 1.07 mmol), 1-bromo-4-(methylthio)benzene (217 mg; 1.07 mmol), 2-dicyclohexylphosphino-2'-(Λ/,Λ/-dimethylamino)biphenyl (113 mg; 0.29 mmol), and Pd2(dba)2 (57 mg; 62 μmol) in degassed 1 ,4-dioxan (5 mL). The mixture was sonicated for 1 minute, and stirred under microwave conditions in a sealed tube at 1000C for 5 minutes. The crude mixture was partitioned between ethyl acetate (40 mL) and water (40 mL), and the separated aqueous extracted with ethyl acetate (40 mL). The combined organic phase was dried (MgSO4), and concentrated in vacuo. The resulting brown oil was purified by column chromatography, giving the title compound 4-[4-(methylthio)phenyl]piperazine- 1-carboxylic acid-terf-butylester as a yellow solid (259 mg; 79%). LC/MS (Ammonium bicarbonate ES+) Found 209 (M-Boc+H). |
75.9% | With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; DavePhos In 1,4-dioxane at 100℃; for 0.5h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With copper(l) iodide; 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran at 50℃; for 20.1667h; | 40 To a degassed solution of 4-bromothioanisole (10.15 g, 50.0 mmol) in tetrahydrofu- ran (50 mL) were in the following order added: copper(l) iodide (286 mg, 1.5 mmol), tetrakis- (triphenylphosphine)palladium (1.73 g, 1.5 mmol), and 1 ,8-diazabicyclo[5.4.0]undec-7-ene (9.05 mL, 60.0 mmol). The resulting mixture was degassed one more time and a solution of propargyl alcohol (3.5 mL, 60.0 mmol) in tetrahydrofuran (5 mL) was added over period of 10 min. The reaction mixture was slowly heated up to 50 °C and then stirred at this temperature over night (~20 h). The mixture was diluted with ether (350 mL) and 5 % hydrochloric acid (100 mL) was added. The mixture was filtered and the phases were separated. The aqueous phase was extracted with ether (2 x 60 mL) and collected ethereal solutions were washed with 1 M hydrochloric acid (30 mL) and saturated aqueous solution of sodium hydrogen carbonate (2 x 50 mL), dried with anhydrous magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography (silica gel Fluka 60, chloroform) affording 3- (4-methylsulfanylphenyl)prop-2-yn-1-ol. Yield: 8.5 g (95 %). RF (SiO2, chloroform): 0.25. 1H NMR spectrum (300 MHz, CDCI3, δH): 7.35 (d, J=8.5 Hz, 2 H); 7.18 (d, J=8.5 Hz, 2 H); 4.50 (d, J=4.9 Hz, 2 H); 2.49 (s, 3 H); 1.94 (m, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | Stage #1: (4-bromophenyl)thioanisole With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: N-[(1E)-(3-bromophenyl)(2-cyanophenyl)methylene]-2-methylpropane-2-sulfinamide In tetrahydrofuran; hexane at -78℃; for 3h; | 2 To a -78°C solution of 4-bromo-thioanisole (0.934 g, 4.6 mmol) in THF (20 mL) was nBuLi (1.6 M in hexane, 2.6 mL, 4.2 mmol) added, after 0.5 h a solution of 7V-[(lE)-(3- bromophenyl)(2-cyanophenyl)methylene]-2-methylpropane-2-sulfinamide (1.5 g, 3.8 mmol) in THF (10 mL) was added. The reaction mixture was stirred at -78°C for 3 h and then quenched by addition OfH2O. EtOAc was added and the mixture was washed with H2O and brine, dried over MgSO4 and concentrated. The residue was dissolved in MeOH (25 mL) and treated with HCl (IM in Et2O, 5.0 mL, 5.0 mmol) over night. The reaction mixture was concentrated and then partitioned between NaHCO3 (sat.) and CHCl3, the organic phase was dried over MgSO4 and concentrated. The residue was purified by flash chromatography using a gradient of MeOH in EtOAc to give the title compound (1.3 g, 79%): 1U NMR (400 MHz, DMSO-J6) δ ppm 7.74 - 7.83 (m, 1 H), 7.63 - 7.70 (m, 1 H), 7.37 - 7.49 (m, 4 H), 7.26 - 7.32 (m, 1 H), 7.11 - 7.25 (m, 5 H), 6.84 (br s, 2 H), 2.42 (s, 3 H); MS (AP) m/z 408, 410 [M+l]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | (Example 66) 5-Hydroxymethyl-2-(4-methylsulfanylbenzyl)phenyl 7-deoxy-D-glycero-beta-D-gluco-heptopyranoside (Example Compound No. 1-135); (66a) Methyl 3-hydroxy-4-[hydroxy-(4-methylsulfanylphenyl)methyl]benzoate; 4-Bromothioanisole (9.02 g, 44.4 mmol) was dissolved in tetrahydrofuran (50 mL), followed by addition of magnesium (1.08 g, 44.4 mmol) and a catalytic amount of iodine, and the mixture was stirred at room temperature for 30 min and further heated to reflux for 1 h. The reaction mixture was added dropwise to a solution of 2-hydroxy-4-methoxycarbonylbenzaldehyde (2.00 g, 11.1 mmol) in tetrahydrofuran (40 mL) at -50C, and the mixture was stirred from -50 to 2C for 1 h. Aqueous ammonium chloride was added to the reaction mixture, the mixture was extracted with ethyl acetate, and then the organic layer was washed with saturated brine. The organic layer was dried over anhydrous sodium sulfate, and then the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate, 3:1 to 2:1, v/v) to obtain the title compound (3.38 g, yield 100%) as a yellow oil. 1H NMR (400 MHz, CDCl3): delta 2.48 (3H, s), 2.89 (1H, d, J=3.1 Hz), 3.89 (3H, s), 6.04 (1H, d, J=3.1 Hz), 6.96 (2H, d, J=7.8 Hz), 7.25 (2H, d, J=8.6 Hz), 7.31 (2H, d, J=8.6 Hz), 7.49 (1H, dd, J=7.8 and 1.6 Hz), 7.56 (1H, d, J=1.6 Hz), 8.00 (1H, s); MS (FAB)m/z: 304 (M)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With bis(triphenylphosphine)nickel(II) chloride; lithium hexamethyldisilazane In toluene at 100℃; for 2h; Glovebox; Sealed tube; | |
91% | With bis(tri-ortho-tolylphosphine)palladium(0); (R)-(-)-1-[(S)-2-(dicyclohexylphosphino)ferrocenyl]ethyl-di-tert-butylphosphine; ammonia; sodium t-butanolate In 1,4-dioxane at 90℃; for 15h; Inert atmosphere; | |
81% | With dicyclohexyl(2',4',6'-triisopropyl-5-methoxy-3,4,6-trimethyl-[1,1'-biphenyl]-2-yl)phosphine; C50H70NO4PPdS; C50H70NO4PPdS; dicyclohexyl(2',4',6'-triisopropyl-4-methoxy-3,5,6-trimethyl-[1,1'-biphenyl]-2-yl)phosphine; ammonia; sodium t-butanolate In 1,4-dioxane at 20℃; for 36h; Inert atmosphere; |
54% | Stage #1: (4-bromophenyl)thioanisole With magnesium In tetrahydrofuran Inert atmosphere; Stage #2: With C10H17NO In tetrahydrofuran; toluene at -78℃; for 2h; Inert atmosphere; Stage #3: With ammonium chloride In tetrahydrofuran; water; toluene Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With racemic-2-(di-tert-butylphosphino)-1,1′-binaphthyl; palladium diacetate; zinc In N,N-dimethyl-formamide at 110℃; for 1h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With tris(2,4-pentanedionato)iron(III); tert-butylmagnesium chloride In tetrahydrofuran at 0℃; for 1.5h; Inert atmosphere; | |
58% | With isopropanol for 24h; Schlenk technique; Inert atmosphere; Irradiation; Heating; | |
45 %Chromat. | With hydrogen; triethylamine In methanol; water monomer at 120℃; for 130h; Autoclave; |
81 %Spectr. | With N-ethyl-N,N-diisopropylamine In acetonitrile for 16h; Irradiation; | |
Multi-step reaction with 2 steps 1.1: n-butyllithium / tetrahydrofuran; n-Pentane / 1 h / -78 °C / Inert atmosphere 1.2: 18 h / -78 - 20 °C / Inert atmosphere 2.1: 9-mesityl-10-methylacridin-10-ium perchlorate; 2-phenylmalononitrile / 1,2-dichloro-ethane; 2,2,2-trifluoroethanol / 24 h / 20 °C / Irradiation; Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With 1,10-Phenanthroline; oxygen; potassium bromide; copper(ll) bromide In N,N-dimethyl-formamide at 130℃; for 20h; | General procedure: under oxygen, a sealed reaction tube was charged with KX (X = I, Br) (0.2 mmol), arylboronic acid (0.3 mmol), CuBr2 (4.5 mg, 10 mol %), 1,10-phen (7.2 mg, 20 mol %) and DMF (2 mL). The mixture was stirred at 80 or 130 °C. After the completion of the reaction, the solvent was evaporated under reduced pressure and the residue was purified by flash column chromatography on silica gel to give the product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
(2) n-Butyllithium (2.64 M, 2.9 mL) was added to a solution of 4-bromothioanisole (1.61 g) in tetrahydrofuran (20 mL) at -78 C. in a nitrogen atmosphere, and the mixture was stirred at the same temperature for 30 minutes. A solution of <strong>[1211527-87-5]5-chloro-6-methoxypyridine-2-carbaldehyde</strong> (1.14 g) in tetrahydrofuran (10 mL) was added to the reaction solution, followed by stirring for one hour. The reaction solution was poured into a saturated ammonium chloride solution, followed by extraction with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and filtered, after which the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:1?4:1) to give (5-chloro-6-methoxypyridin-2-yl)[4-(methylsulfanyl)phenyl]methanol as a pale yellow oil (1.42 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | Stage #1: (4-bromophenyl)thioanisole With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 2h; Stage #2: 1-(4-fluorophenyl)ethanone In tetrahydrofuran; hexane at -70℃; for 10h; Stage #3: With toluene-4-sulfonic acid In dichloromethane at 20℃; for 10h; | Preparation of (4-(1-(4-bromophenyl)vinyl)phenyl)(methyl)sulfane 6l A dry two-necked round bottom flask was charged with (4-bromophenyl)(methyl)sulfane (2.03 g, 10 mmol) in dry tetrahydrofuran (15 mL), the solution was cooled to -78 °C. BuLi (6 mL, 2 M in hexane solution, 12 mmol) was added dropwise to the solution. The mixture was stirred at -78 °C for 2 h. Then 1-(4-fluorophenyl)ethanone (1.38 g, 10 mmol) in dry tetrahydrofuran (5 mL) was added slowly and the reaction mixture was stirred at -70 °C for 10 h. Saturated aqueous NH4Cl solution (2 mL) was added. The mixture was allowed to warm to room temperature for 1 h. The resulting solution was concentrated under vacuum, poured into water (20 mL), and was extracted with DCM (3*15 mL). The organic layer was dried over MgSO4, filtered, and p-TsOH (20 mg) was added to the filtration. The solution was stirred at room temperature for 10 h. The residue was purified by silica gel flash chromatography (20:1 hexane-EtOAc) to give 2 g of the desired product in 82% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | Stage #1: (4-bromophenyl)thioanisole With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 2h; Stage #2: acetophenone In tetrahydrofuran; hexane at -70℃; for 10h; Stage #3: With toluene-4-sulfonic acid In dichloromethane at 20℃; for 10h; | Preparation of methyl (4-(1-phenylvinyl)phenyl)sulfane 6b A dry two-necked round bottom flask was charged with (4-bromophenyl)(methyl)sulfane (2.03 g, 10 mmol) in dry tetrahydrofuran (15 mL), the solution was cooled to -78 °C. BuLi (6 mL, 2 M in hexane solution, 12 mmol) was added dropwise to the solution. The mixture was stirred at -78 °C for 2 h. Then acetophenone (1.2 g, 10 mmol) in dry tetrahydrofuran (5 mL) was added slowly and the reaction mixture was stirred at -70 °C for 10 h. Saturated aqueous NH4Cl solution (2 mL) was added. The mixture was allowed to warm to room temperature for 1 h. The resulting solution was concentrated under vacuum, poured into water (20 mL), and was extracted with DCM (3*15 mL). The organic layer was dried over MgSO4, filtered and p-TsOH (20 mg) was added to the filtration. The solution was stirred at room temperature for 10 h. The residue was purified by silica gel flash chromatography (20:1 hexane-EtOAc) to give 2 g of the desired product in 88% yield. |
50% | Stage #1: (4-bromophenyl)thioanisole With iodine; magnesium In tetrahydrofuran; hexane Reflux; Stage #2: acetophenone In tetrahydrofuran at 0℃; for 10h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Stage #1: (4-bromophenyl)thioanisole With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 2h; Stage #2: 1-(4-methoxyphenyl)ethanone In tetrahydrofuran; hexane at -70℃; for 10h; Stage #3: With toluene-4-sulfonic acid In dichloromethane at 20℃; for 10h; | Preparation of (4-(1-(4-methoxyphenyl)vinyl)phenyl)(methyl)sulfane 6j A dry two-necked round bottom flask was charged with (4-bromophenyl)(methyl)sulfane (2.03 g, 10 mmol) in dry tetrahydrofuran (15 mL), the solution was cooled to -78 °C. BuLi (6 mL, 2 M in hexane solution, 12mmol) was added dropwise to the solution. The mixture was stirred at -78 °C for 2 h. Then 1-(4-methoxyphenyl)ethanone (1.5 g, 10 mmol) in dry tetrahydrofuran (5 mL) was added slowly and the reaction mixture was stirred at -70 °C for 10 h. Saturated aqueous NH4Cl solution (2 mL) was added. The mixture was allowed to warm to room temperature for 1 h. The resulting solution was concentrated under vacuum, poured into water (20 mL), and was extracted with DCM (3*15 mL). The organic layer was dried over MgSO4, filtered, and p-TsOH (20 mg) was added to the filtration. The solution was stirred at room temperature for 10 h. The residue was purified by silica gel flash chromatography (20:1 hexane-EtOAc) to give 2 g of the desired product in 80% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With dmap; bis(η3-allyl-μ-chloropalladium(II)); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In 1,3,5-trimethyl-benzene at 140℃; for 20h; Inert atmosphere; | 4.2. Pd-catalyzed decarboxylative cross-couplings of potassium malonate monoesters with aryl halides General procedure: after standard cycles of evacuation and back-filling with dry and pure nitrogen, an oven-dried Schlenk tube equipped with a magnetic stirring bar was charged with Pd source (see Table 1, Table 2, Table 3 and Table 4), ligand (see Table 1, Table 2, Table 3 and Table 4), N,N-dimethylpyridin-4-amine (DMAP, see Table 1, Table 2, Table 3 and Table 4), and ethyl potassium malonate (see Table 1, Table 2, Table 3 and Table 4). The tube was evacuated and backfilled with argon (this procedure was repeated three times). Under a counter flow of argon, aryl halide (see Table 1, Table 2, Table 3 and Table 4) and solvent (see Table 1, Table 2, Table 3 and Table 4) were added by syringe. The tube was sealed and stirred at room temperature for 10 min. Then the tube was connected to the Schlenk line, which was full of argon, stirred in a preheated oil bath (140-150 °C) for the appointed time (20-25 h). Upon completion of the reaction, the mixture was cooled to room temperature and diluted with diethyl ether, and the yields were determined by gas chromatography using 1,3-dimethoxybenzene as the internal standard. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With potassium nitrite; copper(II) bis(trifluoromethanesulfonate) In dimethyl sulfoxide at 130℃; for 48h; Inert atmosphere; Sealed tube; regioselective reaction; | General procedure for copper(II) triflate catalyzed ipso-Nitration of haloarenes presented in Table 2. General procedure: An oven dried pressure tube was charged with haloarenes (0.5 mmol), copper(II) triflate (45 mg, 0.125 mmol), KNO2 (128 mg, 1.5 mmol) and anhydrous DMSO (0.6 mL) under nitrogen atmosphere. The tube was sealed with a teflon screw cap having mininert valve and nitrogen is purged through it for 5 min. It is stirred at room temperature for 10 min and then the temperature was gradually increased to 130 oC and is maintained at the same for 48 h. The reaction mixture was then cooled to room temperature, washed with excess ice cold water and extracted with ethyl acetate (3 x 10 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the crude product which was purified by column chromatography using silica gel (Table 2, entries 1-18) or basic alumina (Table 2, entries 19-23) and a mixture of ethyl acetate and hexane as the eluent to afford the desired products in good yields. |
82% | With potassium nitrite; basolite C300 In dimethyl sulfoxide at 130℃; for 48h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 10h; Inert atmosphere; | 1 Example 1: Preparation of intermediate substituted distyryl methyl sulfide: General procedure: R0 substituted styrene (10mmol), 3-bromobenzyl sulfide or 4-bromobenzyl sulfide(10 mmol), tetrakis(triphenylphosphine)palladium dichloride (0.1 mmol) and potassium carbonate(10 mmol) was added to 50 mL of DMF solution and placed in a 100 ° C oil bath under nitrogen.Stir the reaction for 10 h, concentrate the solvent under reduced pressure, and add 100 mL of deionized water.The precipitate precipitated by suction filtration was dissolved in 50 mL of dichloromethane, and the catalyst was recovered by a short silica gel column.The filtrate was evaporated to dryness and then recrystallized from anhydrous ethanol to give a white powder. |
63% | With triethanolamine; palladium diacetate for 10h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With palladium diacetate; tricyclohexylphosphine In tetrahydrofuran at 40℃; for 1h; Inert atmosphere; | 4.3.3. (4-Benzylphenyl)(methyl)sulfane (3c)12c General procedure: To a reaction vessel containing Pd(OAc)2 (2.2 mg, 0.010 mmol), PCy3 (5.6 mg, 0.020 mmol), and an aromatic or a heteroaromatic bromide (1.00 mmol) in 0.5 mL THF was added a solution of (ArCH2)Ti(O-i-Pr)3 (1.50 mmol) in 0.5 mL THF. The mixture was reacted at 40 or 80 °C for a given period of time under a dry nitrogen atmosphere. The solution turned dark black and was quenched with 10 mL of water. The solution was extracted with dichloromethane (3×30 mL). The organic phase was dried over anhydrous magnesium sulfate, concentrated to dryness, and purified by column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With water; palladium diacetate; potassium carbonate; catacxium A In dimethyl sulfoxide at 120℃; for 16h; Inert atmosphere; Autoclave; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With C28H41ClNPPd; caesium carbonate In toluene at 100℃; for 24h; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With tetramethyl ammonium acetate In methanol; acetonitrile at 20℃; Electrochemical reaction; | |
With N-Bromosuccinimide; potassium <i>tert</i>-butylate In methanol at 20℃; for 2h; Inert atmosphere; | 8.1 Step 1: N-Cyano-S-methyl-S-(4-bromophenyl)sulfilimine Step 1: N-Cyano-S-methyl-S-(4-bromophenyl)sulfilimine A mixture of 4-bromothioanisole (3.75 g), cyanamide (1.01 g), potassium tert-butoxide (2.49 g), and N-bromosuccinimide (4.93 g) in methanol (75 mL) is stirred at room temperature under an argon atmosphere for 2 h. The reaction mixture is concentrated in vacuo, diluted with water, and extracted ethyl acetate. The combined extracts ware washed with brine, dried over MgSO4, and concentrated in vacuo. The residue is triturated with ethyl acetate and the precipitate is filtered off, washed with small amounts of ethyl acetate and tert-butylmethyl ether, and dried to yield the title compound. LC (method 1): tR=1.10 min; Mass spectrum (ESI+): m/z=243 [M+H]+. | |
With N-Bromosuccinimide; potassium <i>tert</i>-butylate In methanol at 20℃; for 2h; Inert atmosphere; | 8.1 N-Cyano-S-methyl-S-(4-bromophenyl)sulfilimine A mixture of 4-bromothioanisole (3.75 g), cyanamide (1 .01 g), potassium tert- butoxide (2.49 g), and N-bromosuccinimide (4.93 g) in methanol (75 mL) is stirred at room temperature under an argon atmosphere for 2 h. The reaction mixture is concentrated in vacuo, diluted with water, and extracted ethyl acetate. The combined extracts ware washed with brine, dried over MgS04, and concentrated in vacuo. The residue is triturated with ethyl acetate and the precipitate is filtered off, washed with small amounts of ethyl acetate and tert-butyl methyl ether, and dried to yield the title compound. LC (method 1 ): tR = 1.10 min; Mass spectrum (ESI): m/z = 243 [M+H]+ |
With [bis(acetoxy)iodo]benzene In acetonitrile | ||
With N-Bromosuccinimide; potassium <i>tert</i>-butylate In methanol at 20℃; Inert atmosphere; | 2 EXAMPLE 2. General procedure for the synthesis of intermediates of formula (III) (See Scheme 1). General procedure: N-bromosuccinimide (1.5 equiv) was added to a solution of the corresponding intermediate of formula (II) (1.0equiv), potassium tert-butoxide (1.2 equiv) and cyanamide (1.3 equiv) in anhydrous methanol (5 mL/mmol) under anargon atmosphere, and the reaction mixture was stirred at rt until consumption of the starting material. Next, the solventwas evaporated under reduced pressure and the resulting residue was partitioned between DCM and water. The aqueousphase was extracted with DCM (x2) and the combined organic layers were dried over Na2SO4, filtered and evaporatedunder reduced pressure to afford the corresponding N-cyanosulfylimine, which was used in the next step without furtherpurification. [(4-Bromophenyl)(methyl)oxido-λ6-sulfanylidene]cyanamide (IIIa). Following the previous general procedure,intermediate IIIa was obtained starting from 1-bromo-4-(methylsulfanyl)benzene (0.69 g, 3.39 mmol) as a solid (0.73 g,83% for 2 steps). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With lithium hydroxide monohydrate; [N-((pyridin-2-ylmethyl)carbamothioyl)benzamide]; palladium diacetate In N,N-dimethyl-formamide at 130℃; for 10h; | General procedure for Heck reaction of aryl bromides with styrene: General procedure: The 25 mL RB flask was charged with aryl bromides (1 mmol), alkenes (2 mmol), LiOHH2O(2 mmol), and the catalyst (Pd(OAc)2/1a = 1:2, 0.001 mol % in 2 mL N,Ndimethylformamide).The reaction mixture was heated at 130 C for 10 h.Then the reaction mixture was cooled to room temperature, diluted with ethylacetate (20 mL), and washed with brine water. The combined organic phasewas dried over anhydrous Na2SO4. After removal of the solvent, the residuewas subjected to column chromatography on silica gel using ethyl acetate andhexane to afford the Heck product in high purity. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; sodium t-butanolate; In toluene; at 110℃;Inert atmosphere; Reflux; | ieri-Butyl-4-methyl-4-(4-(methylthio)phenylamino)piperidine-1 -carboxylate To a solution of ferf-butyl 4-amino-4-methylpiperidine-1 -carboxylate (22 mg, 0.10 mmol) in toluene (5 mL) was added sequentially (4-bromophenyl)(methyl)sulfane (22 mg, 0.11 mmol), 4,5-bis(diphenylphosphino)- 9,9-dimenthxanthene (Xantphos) (5 mg, 0.008 mmol), tris(dibenzylideneacetone)dipalladium(0) (5 mg, 0.005 mmol) and sodium ferf-butoxide (20 mg, 0.2 mmol) under argon an atmosphere. The resulting mixture was stirred for 15 minutes before was refluxed at 110C overnight. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with ethyl acetate : petroleum ether = 3:1 to afford ferf-butyl-4-methyl-4-(4- (methylthio)phenylamino)piperidine-1 -carboxylate (15 mg, 48%) as a yellow oil. LCMS (ESI): m/z = 337.2 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | Stage #1: 4,4',5,5'-tetrahydro-7,7'-spirobi[thieno[2,3-c]pyran] With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Schlenk technique; Inert atmosphere; Stage #2: With zinc(II) chloride In tetrahydrofuran; hexane at -78 - 0℃; for 1h; Schlenk technique; Inert atmosphere; Stage #3: (4-bromophenyl)thioanisole With tetrakis(triphenylphosphine) palladium(0) In tetrahydrofuran; hexane at 50℃; for 6h; Schlenk technique; Inert atmosphere; | Palladium-Catalyzed Cross-Coupling Reactions of Organozinc Reagent 14 with Various Electrophiles 10d-o; Typical Procedure 2 (TP2) General procedure: A dry, argon-flushed Schlenk flask equipped with a magnetic stirring bar and a septum was charged with spiro compound 1 (0.38 mmol. 1.0 equiv) in anhyd THF (3 mL) and cooled to -78 °C for 10 min. 2.48M n-BuLi in hexane (0.42 mmol, 1.1 equiv) was added and the mixture was stirred at -78 °C for 1 h until GC analysis of reaction aliquots showed full consumption of the starting material. 1 M ZnCl2 in THF solution (0.46 mmol, 1.2 equiv) was added and the mixture was stirred at -78 to 0 °C for 1 h. An aryl bromide or acid chloride 10d-o(0.30 mmol, 0.8 equiv) and Pd(PPh3)4 (0.015 mmol, 0.05 equiv, 5mol%) were added and the mixture was stirred at 50 °C for 3-6 h. The mixture was quenched with sat. aq NH4Cl solution (5 mL) and extracted with EtOAc (4 × 15 mL). The combined organic phases were dried (Na2SO4) and concentrated in vacuo. The crude residue obtained was purified by flash column chromatography (silica gel pre-neutralizedwith Et3N, isohexane-EtOAc) to give the analytically pure spiroproduct 11d-o. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With pyridine-4-carbonitrile; bis(pinacol)diborane In pentane at 80℃; for 36h; Inert atmosphere; Sealed tube; | |
60% | With triethylsilane; tris(pentafluorophenyl)borate In neat (no solvent) at 100℃; for 8h; Glovebox; Inert atmosphere; | Reduction of Sulfoxides and Sulfones; General Procedure General procedure: In a glovebox, an oven-dried 1-mL screw-capped sealed tube with a magnetic stir bar was charged with B(C6F5)3 (10 mol%), Et3SiH (10 equiv), and the indicated oxidized sulfur compound (0.20 mmol). The tube was sealed properly and transferred to an oil bath preheated at100 °C. After 8 h, the reaction was cooled to r.t. and passed through asmall plug of silica gel using Et2O. The crude material was collected ina glass vial and subjected to GLC analysis to determine the conversion with respect to starting material. The ethereal solution was dried (Na2SO4) and filtered, and the solvent was removed under reduced pressure. The mixture was then subjected to high vacuum at 70 °C until the unreacted hydrosilane was removed from the system. If needed, the residue was purified further by flash column chromatography (silica gel, cyclohexane/Et2O 9:1) to afford the desired sulfides. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | With 2-di-tertbutylphosphino-3,4,5,6-tetramethyl-2',4',6'-triisopropyl-1,1'-biphenyl; potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); In toluene; at 120℃; for 4.5h;Inert atmosphere; | A dried flask was equipped with a magnetic stir bar and charged with [Pd2(dba)3] (22.5 mg, 24.6 muiotaetaomicron, Eq: 0.01) and di-tert-butyl(2',4',6'-triisopropyl-3,4,5,6-tetramethyl-[l,l'- biphenyl]-2-yl)phosphine (23.7 mg, 49.2 mumol, Eq: 0.02). The flask was evacuated and backfilled with Ar (3x). Toluene (1.5 mL) was added, and the resulting mixture was stirred for 3 min at 120 °C (until the colour turns from dark-purple to dark brown). A second previously dried flask was equipped with a stir bar, and charged with K3P04 (1.05 g, 4.92 mmol, Eq: 2) and ethyl 2H-l,2,3-triazole-4-carboxylate (example 23a; 417 mg, 2.95 mmol, Eq: 1.2). The flask was evacuated and filled with Ar. (4-Bromophenyl)(methyl)sulfane (500 mg, 2.46 mmol, Eq: 1) was then added, as well as the premixed catalyst solution and toluene (1.5 mL). The resulting mixture was heated at 120 °C for 4.5h. The reaction was cooled down to 25 °C, diluted with EtOAc, washed with brine, dried over Na2S04, filtered, and evaporated. MPLC (Si02; heptane/EtOAc, gradient from 100:0 to 50:50 within 20 min) gave the title compound (196 mg, 30percent) as a yellow solid. MS (ESI): m/z = 264.1 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84.8% | Stage #1: ethyl O-(2-mesitylenesulfonyl)acetohydroxamate With perchloric acid In dimethyl sulfoxide at 0℃; Stage #2: (4-bromophenyl)thioanisole In dichloromethane at 0℃; | 61 Compound 204 (7.14 g, 25.01 mmol) was dissolved in DMSO (25 ml), to which was then added dropwise perchloric acid (70 wt%, 27 ml, 291 mmol) under ice cooling, and the resulting mixture was stirred at 0°C. The reaction mixture was extracted with dichloromethane, which was then dried over magnesium sulfate and filtered. (0415) Into another reaction vessel were placed Compound 203 (5.08 g, 25.01 mmol) and dichloromethane (25 ml), and the filtrate was added dropwise under ice cooling. The reaction mixture was stirred at 0°C, and then concentrated under reduced pressure. To the residue was added diethyl ether to precipitate Compound 205, and Compound 205 (8.87 g, 84.8%) was obtained as solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | Stage #1: (4-bromophenyl)thioanisole With iodine; magnesium In tetrahydrofuran Stage #2: of tert-butyl (4S)-4-(4-((3-formyl-2,2-dimethylchroman-4-yl)oxy)benzyl)-2,2-dimethyloxazolidine-3-carboxylate In tetrahydrofuran at 20℃; | (ii) General procedure for the preparation of carbinols 9-11 General procedure: A dried 100 ml double-necked round bottom flask was charged with magnesium (2 eq), pinch of iodine and after flushing with nitrogen, dried and THF was added and stirred for 10 min. Then corresponding bromo compound (1.5 eq) was added, the color of iodine disappeared slowly indicating the formation of Grignard reagent. After complete disappearance of color, it was stirred for one hour and then corresponding carbaldehye 8 (1 eq) was added under ice-cold condition and stirred at room temperature. Completion of reaction was determined by TLC. Reaction was quenched by NH4Cl solution at 0 0C. Organic layer was extracted thrice with ethyl acetate and combined organic layers were dried with magnesium sulphate and concentrated under reduced pressure and finally purified by column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69.73% | Stage #1: 4-methylsulfanylaniline With 1,1'-bis-(diphenylphosphino)ferrocene; tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate In toluene at 60℃; for 0.5h; Stage #2: (4-bromophenyl)thioanisole In toluene at 90℃; for 12h; Inert atmosphere; | 1 Synthesis of bis(4-(methylthio)phenyl)amine (compound of formula IV) 4-Aminothioanisole (Formula VII, 3.34 g, 24 mmol), sodium tert-butoxide (2.69 g, 28 mmol), tris(dibenzylideneacetone)dipalladium (0.366 g, 0.4 mmol), 1,1'-bis(diphenylphosphino)ferrocene (DPPF) (0.332 g, 0.6 mmol) was mixed with 20 ml of toluene, and stirred at 60 °C for 30 min. Add 4.06 g of 4-bromobenzyl sulfide (Form VI, 4.06 g, 20 mmol) was then refluxed at 90 °C for 12 hours under nitrogen. Cool the reaction mixture to room temperature, add deionized water, BThe acid ethyl ester was extracted three times, and the organic phase was combined, then washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and evaporated in vacuo. After the solvent, Purification by column chromatography with ethyl acetate/petroleum ether (1/15, ν/ν) gave 3.64 g of a yellow solid bis((methylthio).Phenyl)amine, yield: 69.73% |
63.6% | With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate In toluene at 110℃; for 48h; Inert atmosphere; | 4 Put 1 g of 1-bromo-4-(methylsulfanyl)benzene, 0.4 g 4-(methylsulfanyl)aniline,65 mg of Pd2(dba)3 and 2.84 g of sodium tert-butoxide were added to a 100 mL reaction flask, which was purged with nitrogen three times, then 60 mL of anhydrous oxygen-free toluene and 280 μl of 1 M tris were added. Butylphosphine toluene solution,Stir at 110 °C for 48 hours. After the reaction is completed, it is cooled to room temperature.Toluene was distilled off under reduced pressure, the remaining mixture was dissolved in 80 mL of dichloromethane, and the organic layer was washed three times with 50 mL of water.Then, the organic layer was dried over anhydrous magnesium sulfate and filtered to obtain a filtrate.The filtrate was evaporated to dryness under reduced pressure to give crude product with petroleum ether and BColumn chromatography with ethyl acetate volume ratio 10:1 as eluent,0.820 g of 4-(methylsulfanyl)-N-[4-(methylsulfanyl)phenyl]anilinewas obtained as a white solid with a yield of 63.6%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With [CoBr2(N-(1-(pyridin-2-yl)ethylidene)quinolin-8-amine)]; 3-chloroprop-1-ene; trifluoroacetic acid; zinc dibromide; zinc In acetonitrile at 50℃; for 24h; | One-Pot Synthesis of Biaryls; General Procedure 2 (GP2) General procedure: An oven-dried flask was equipped with a stirring bar and closed witha septum. Zinc dust (1.08 g, 16.5 mmol, 3.33 equiv), ZnBr2 (146 mg,0.65 mmol, 0.13 equiv) and Co(II) catalyst were added and stirred in CH3CN (4 mL). TFA (0.1 mL, 1.3 mmol, 0.26 equiv) and allyl chloride (0.17 mL, 2.05 mmol, 0.4 equiv) were added subsequently which caused a rise in temperature and gas evolution. Pyridine was added if necessary. Once the mixture again reached r.t., the two aryl halides were added and the reaction mixture was stirred at the indicated temperature 50 °C until iodolyzed aliquots showed full conversion of the starting material (GC analysis). The reaction was quenched by addition of saturated aqueous NH4Cl solution (20 mL) which was followed by extraction with DCM (3 × 50 mL). The combined organic layers were dried over MgSO4 and, after filtration, the solvents were evaporated in vacuo. Purification by flash column chromatography furnished the desired biaryls. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With chloro(2’-amino-1,1’-biphenyl-2-yl)palladium(II) dimer; C60H54NO5P; sodium hydride In toluene at 100℃; for 12h; Inert atmosphere; enantioselective reaction; | Typical Procedure for the synthesis of compounds 2, 3, 4, 5 and 6 (Typical Procedure C) General procedure: Under nitrogen atmosphere, a mixture of alcohol 1a (28.6 mg, 0.10 mmol, 1.0 equiv), 4-bromoanisole (37.4 mg, 0.20 mmol, 2.0 equiv), [C12H8NH2PdCl]2 (1.5 mg, 2.5 mol%), L10 (13.6 mg, 15 mol%) and NaH (7.2 mg, 0.30 mmol, 3.0 equiv) in anhydrous toluene (2.0 mL), were heated at 80°C for 12 h. After being cooled to room temperature, the solvent was removed and the residue was purified by flash chromatography on silica gel (hexanes/ethyl acetate = 30:1) to afford the desired product 2a (38.0 mg, 97%, 96% ee). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With palladium diacetate; potassium carbonate; bis[2-(diphenylphosphino)phenyl] ether In 1,4-dioxane at 130℃; for 5h; Inert atmosphere; Schlenk technique; Sealed tube; regioselective reaction; | |
62% | With palladium diacetate; potassium carbonate; bis[2-(diphenylphosphino)phenyl] ether In 1,4-dioxane at 130℃; for 5h; Inert atmosphere; Sealed tube; | 1 General procedure: In a dry sealed tube, protected by argon, add 3.4mg Pd(OAc)2, 16.2mg DPEPhos, 77.4mg 1a(0.3mmol), 47.1μL 2a(0.45mmol), 82.8mg K2CO3, 1.5mL dioxane, and heat to 130 , stir for 5h. It was cooled to room temperature and concentrated. The residue was column chromatographed with n-hexane as the eluent, and the product band was collected to obtain 65 mg of 3aa white solid with a yield of 85%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With tetrabutylammomium bromide; copper(II) acetate monohydrate; potassium hydroxide In water at 100℃; for 12h; Sealed tube; | (Het)aryl Methyl Sulfides; General Procedure General procedure: A 25-mL sealable tube was charged with the appropriate aryliodide or bromide (1.0 mmol), dimethyl disulfide (1.2 mmol),Cu(OAc)2·H2O (0.1 mmol), KOH (2.0 mmol), TBAB (0.05 mmol),and H2O (2.0 mL). The mixture was stirred at 100 °C (130 °C forbromides) for 12 h under air then cooled to r.t. The mixture wasdiluted with H2O (5 mL) and extracted with EtOAc (4 × 10 mL).The extracts were combined, washed with brine (3 × 10 mL),dried (MgSO4), filtered, and concentrated. The residue was purifiedby chromatography [silica gel, EtOAc-hexane (1:30 to1:100)]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | Stage #1: 1-bromo-4-(trifluoromethoxy)benzene With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; 2,2'-bis(1,3,2-benzodioxaborole); potassium acetate In ethanol; ethylene glycol at 80℃; for 2.5h; Inert atmosphere; Stage #2: (4-bromophenyl)thioanisole With potassium phosphate tribasic trihydrate In ethanol; ethylene glycol; dimethyl sulfoxide at 80℃; for 18h; | 44 In a reaction vessel substituted with argon2,2'-bi (1,3,2-benzodioxaborol)(1.10 mmol, 262 mg), dichloro [1,1'-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00)mmol, 294 mg), ethanol (6.0 mL) and 1-bromo-4- (trifluoromethoxy) benzene (1.00 mmol, 241 mg) were added, and the mixture was stirred at 80 ° C. for 2 hours. Add 1,2-ethanediol (2.20 mmol, 137 mg) to the resulting reaction solution.In addition, the mixture was stirred at 80 ° C. for 30 minutes.Then, potassium phosphate trihydrate (3.00 mmol, 798 mg), 4-bromothioanisole (1.00 mmol, 203 mg) and dimethyl sulfoxide (2.0 mL) were added, and the mixture was further stirred at 80 ° C. for 18 hours.After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to make a colorless transparent liquid.4'-trifluoromethoxy-4-methylthio-1,1'-biphenyl was obtained (219 mg, 77% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | Stage #1: bromochlorobenzene With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; 2,2'-bis(1,3,2-benzodioxaborole); potassium acetate In ethanol; ethylene glycol at 80℃; for 2.5h; Inert atmosphere; Stage #2: (4-bromophenyl)thioanisole With potassium phosphate tribasic trihydrate In ethanol; ethylene glycol; dimethyl sulfoxide at 80℃; for 18h; | 41 In a reaction vessel substituted with argon2,2'-bi (1,3,2-benzodioxaborol)(1.10 mmol, 262 mg), dichloro [1,1'-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00)mmol, 294 mg), ethanol (6.0 mL) and1-Bromo-4-chlorobenzene (1.00 mmol, 191 mg) was added, and the mixture was stirred at 80 ° C. for 2 hours. 1,2-Ethandiol (2.20 mmol, 137 mg) was added to the obtained reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Then potassium phosphate trihydrate (3.00 mmol, 798 mg), 4-bromothioanisole (1.00 mmol, 203 mg) and dimethyl sulfoxide (2)... 0 mL) was added, and the mixture was further stirred at 80 ° C. for 18 hours. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, insoluble matter was removed by filtration, and the filtrate was concentrated. Silica gel chromatograph of the obtained residuePurification by imaging gave 4-chloro-4'-methylthio-1,1'-biphenyl as a colorless and transparent liquid (176 mg, 75% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | Stage #1: 3,4,5-trifluoro-1-bromobenzene With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; 2,2'-bis(1,3,2-benzodioxaborole); potassium acetate In ethanol; ethylene glycol at 80℃; for 2.5h; Inert atmosphere; Stage #2: (4-bromophenyl)thioanisole With potassium phosphate tribasic trihydrate In ethanol; ethylene glycol; dimethyl sulfoxide at 80℃; for 18h; | 47 In a reaction vessel substituted with argon2,2'-bi (1,3,2-benzodioxaborol)(1.10 mmol, 262 mg), dichloro [1,1'-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00)mmol, 294 mg), ethanol (6.0 mL) and 1-bromo-3,4,5-trifluorobenzene (1.00 mmol, 211 mg) were added and stirred at 80 ° C. for 2 hours. 1,2-Ethylenediol (2.20 mmol, 137 mg) was added to the obtained reaction solution., 80 ° C. for 30 minutes. Then, potassium phosphate trihydrate (3.00 mmol, 798 mg), 4-bromothioanisole (1.00 mmol, 203 mg) and dimethyl sulfoxide (2.0 mL) were added, and the mixture was further stirred at 80 ° C. for 18 hours. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to make a colorless transparent liquid.3,4,5-Trifluoro-4'-methylthio-1,1'-biphenyl was obtained (209 mg, 82% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | Stage #1: 1-Bromo-4-fluorobenzene With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; 2,2'-bis(1,3,2-benzodioxaborole); potassium acetate In ethanol; ethylene glycol at 80℃; for 2.5h; Inert atmosphere; Stage #2: (4-bromophenyl)thioanisole With potassium phosphate tribasic trihydrate In ethanol; ethylene glycol; dimethyl sulfoxide at 80℃; for 18h; | 42 In a reaction vessel substituted with argon2,2'-bi (1,3,2-benzodioxaborol)(1.10 mmol, 262 mg), dichloro [1,1'-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00)mmol, 294 mg), ethanol (6.0 mL) and 1-bromo-4-fluorobenzene (1.00 mmol, 225 mg) were added and stirred at 80 ° C. for 2 hours.1,2-Ethandiol (2.20 mmol, 137 mg) was added to the obtained reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes.Then potassium phosphate trihydrate (3.00 mmol, 798 mg), 4-bromothioanisole (1.00 mmol, 203 mg),Dimethyl sulfoxide (2.0 mL) was added, and the mixture was further stirred at 80 ° C. for 18 hours. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography.Colorless and transparent liquid 4'-trifluoromethyl-4-methylthio-1, 1'-biphenyl was obtained (223 mg, yield 83%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With potassium <i>tert</i>-butylate In acetonitrile at 50℃; for 6h; Sealed tube; | 4.2.1. Synthetic procedures General procedure: Aryl fluorides (1.0 mmol), CH3SSCH3 (1.2 mmol), t-BuOK (3.0 mmol) and CH3CN (2 mL) were taken in a 25-ml sealed tube. The reaction mixture was stirred at 50 C for 6 h under air. After cooling to room temperature, the product was diluted with H2O (5 mL) and extracted with EtOAc (4 × 10 mL). The extracts were combined and washed by brine (3 × 10 mL), dried over MgSO4, filtered, and evaporated, and purified by chromatography on silica gel to obtain the desired products with ethyl acetate/hexane (v/v = 1:301:100). The products were characterized by their spectral and analytical data and compared with those of the known compounds (See supporting information). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With calcium hydroxide In N,N-dimethyl-formamide at 80℃; for 2h; Sealed tube; | General Methylation Procedure A (DMF Conditions) General procedure: A 10-mL glass reaction tube fitted with a resealable Teflon valve wasequipped with a magnetic stir bar and charged with the heteroatomnucleophile substrate (1.0 mmol, 1.0 equiv), Ca(OH)2 (100 mg, 1.35mmol, 1.35 equiv), TMP (0.20 mL, 1.7 mmol, 1.7 equiv), and DMF (1.0mL). The flask was sealed and stirred at 80 °C (or at RT for some thiolsubstrates) until TLC indicated complete conversion. The reaction wasthen worked up as described below. Workup Procedure A After complete conversion, 1 N HCl (5 mL) was added and the mixturewas extracted with CH2Cl2 (10 mL). The organic phase was separated,washed with H2O (20 mL), dried over Na2SO4, filtered, and then concentratedin vacuo. The resulting residue was purified by silica gelcolumn chromatography to afford the desired methylated product.Workup Procedure B After complete conversion, petroleum ether (5 mL) was added, andthe solid was smashed into fine particles using a spatula and sonicatedfor 5 min. The resulting residue was then directly subjected to silicagel column chromatography to afford the desired methylated product.Workup Procedure C After complete conversion, CH2Cl2 (5 mL) was added, and the mixturewas filtered through a pad of Celite, washed with H2O (10 mL), andextracted with EtOAc (5 × 20 mL). The organic phase was separated,dried over Na2SO4, filtered, and concentrated in vacuo. The resultingresidue was purified by silica gel column chromatography to affordthe desired methylated product. |
Tags: 104-95-0 synthesis path| 104-95-0 SDS| 104-95-0 COA| 104-95-0 purity| 104-95-0 application| 104-95-0 NMR| 104-95-0 COA| 104-95-0 structure
[ 18184-69-5 ]
3-Bromo-1-ethanesulfanylbenzene
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[ 19614-16-5 ]
(2-Bromophenyl)(methyl)sulfane
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[ 18184-69-5 ]
3-Bromo-1-ethanesulfanylbenzene
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[ 19614-16-5 ]
(2-Bromophenyl)(methyl)sulfane
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[ 18184-69-5 ]
3-Bromo-1-ethanesulfanylbenzene
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[ 70398-89-9 ]
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H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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