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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Diphenyl disulfide is an endogenous metabolite.
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| CAS No. : | 882-33-7 |
| Formula : | C12H10S2 |
| M.W : | 218.34 |
| SMILES Code : | C1(SSC2=CC=CC=C2)=CC=CC=C1 |
| MDL No. : | MFCD00003065 |
| InChI Key : | GUUVPOWQJOLRAS-UHFFFAOYSA-N |
| Pubchem ID : | 13436 |
| GHS Pictogram: |
|
| Signal Word: | Danger |
| Hazard Statements: | H302-H319-H372-H410 |
| Precautionary Statements: | P501-P273-P260-P270-P264-P280-P391-P314-P337+P313-P305+P351+P338-P301+P312+P330 |
| Class: | 9 |
| UN#: | 3077 |
| Packing Group: | Ⅲ |
* 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 |
|---|---|---|
| 88% | To a cooled (-78 C) solution of 2-iodotoluene (6.00 g, 27.5 mmol, 1.0 eq.) in freshly distilled THF (120 mL) was added t-butyllithium (35.6 mL of a 1.7M solution, 2.2 eq.) dropwise via syringe. The reaction was stirred at -78 C for 2h, followed by addition of phenyl disulfide (6.13 g, 28.1 mmol, 1.02 eq) in 20 mL dry THF. The reaction was slowly warmed to r.t. and stirred overnight. Upon completion, 50 mL of sat'd aqueous Na2CO3 was added. The layers were separated and the aqueous layer was extracted with 3 x 20 mL 4:1 hexane/ethyl acetate mix. The organic layers were combined, washed with sat'd. aq. NaCl (1 x 30 mL), dried over MgSO4 and concentrated. Chromatography on silica gel (100% hexanes eluent) provided 2-(phenylthio)toluene (4.85g, 88%) as a colourless oil. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| To a solution of 1(5g) in THF(100mL) was added n-Butyllithium(3.19mL, 2.71M hexane solution) at -78 °C under N2 atmosphere, then the reaction solution was allowed warm up to -30 °C. After cooling again to -78 °C, diphenylsulfide(10.31g) in THF(40mL) was added to the reaction solution. After termination of this reaction, dilute hydrochloric acid was added to the solution. The solution was partitioned between water and Et2O, extracted with Et2O and washed with brine. The extraction was back extracted with sat.NaHCO3 soln. and the back extraction was washed with Et2O. It was neutralized with conc.HCl and the resulting precipitates were collected by filtration and washed with water to give 2 (6.41g). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 77% | With copper(l) iodide; caesium carbonate; In dimethyl sulfoxide; at 80℃; | A mixture of 2-alkynylaniline 1a-1e (0.2 mmol), dichalcogenide 2a-2e (0.15 mmol), CuI (0.02 mmol), and Cs2CO3 (0.2 mmol) in DMSO (2 mL) was stirred at 80 C under an air atmosphere. After completion of the reaction that was monitored by GC-MS or TLC, 25 mL water was added, and the mixture was extracted with ethyl acetate, the combined organic layers were washed with water (10 mL x 3), dried over anhydrous Na2SO4. After filtration and removal of solvents in vacuum, the residue was purified by silica gel column chromatography to afford the corresponding products. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 81% | With sodium dithionite; water; potassium carbonate; In dimethyl sulfoxide; at 60℃; for 0.75h; | General procedure: A mixture of isatoic anhydride 1 (0.6 mmol), disulfide 2 (0.2 mmol), and Na2S2O4 (0.9 mmol) in undried DMSO (2 mL) was stirred at 60 C for respective time in Table 2 and Scheme 2. After the completion of the reaction, as monitored by TLC and GC-MS analysis, the reaction mixture washed with brine and extracted with ethyl acetate. The organic phase was separated and dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated and the resulting residue was purified by column chromatography on silica gel (300-400 mesh) with petroleum ether-EtOAc as eluent to provide the desired product. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 63% | With potassium iodide; In dichloromethane; at 20℃; for 2h; | General procedure: DIB (0.6 mmol, 193 mg), ArSSAr (0.3 mmol), and KI (0.5 mmol, 83 mg) were added to a styrene (or their derivatives) solution in CH2Cl2 (0.5 mmol in 2 mL of CH2Cl2), and the suspension mixture was vigorously stirred at room temperature for 2 h. Upon completion, the reaction mixture was quenched by the addition of saturated aqueous sodium thiosulfate (Na2S2O3) (5 mL), and basified with saturated aqueous sodium hydrogen carbonate (NaHCO3) (5 mL). Further stirring was followed by extraction with ethyl acetate (3*15 mL). The combined organic extracts were washed with water (20 mL), brine (20 mL), dried (anhydrous MgSO4), filtered, and concentrated (aspirator). The residue was purified by column chromatography (SiO2) to furnish analytically pure product. 4.2.11 1-(3-Formylphenyl)-2-(phenylthio)ethyl acetate (3ka) m-Vinylbenzaldehyde (1k) (67 mg, 0.51 mmol). Column chromatography (silica gel; 10% EtOAc/hexanes) yields 3ka (95 mg, 63%); light yellow viscous oil; Rf (10% EtOAc/hexanes) 0.18; IR (neat): νmax 2730, 1744, 1699, 1229 cm-1; 1H NMR (300 MHz, CDCl3): δ 10.00 (s, 1H, CHO), 7.88-7.80 (m, 2H, ArH), 7.60 (d, J=7.7 Hz, 1H, ArH), 7.51 (dd, J=7.7, 7.5 Hz, 1H, ArH), 7.37 (br d, J=7.2 Hz, 1H, ArH), 7.33-7.18 (m, 3H, ArH), 5.95 (dd, J=7.5, 5.9 Hz, 1H, ArCH), 3.45 (dd, J=14.0, 7.5 Hz, 1H, CHH), 3.27 (dd, J=14.0, 5.9 Hz, 1H, CHH), 2.05 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3): δ 191.7, 169.8, 140.0, 136.5, 135.0, 132.7, 130.2, 129.7, 129.1, 129.0, 127.4, 126.7, 73.9, 39.7, 20.8; HRMS (ESI-TOF): MNa+, found: 323.0719; error=0.3 ppm requires C17H16NaO3S 323.0718. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 37% | With copper(l) iodide; XPhos; In dimethyl sulfoxide; at 120℃; for 24h;Sealed tube; Schlenk technique; | General procedure: Under an air atmosphere, a reaction tube was charged with 2-(1H-pyrrol-1-yl)pyridine (1a) (0.2 mmol), diphenyldisulfane (2a) (0.4 mmol), CuI (10 mol%), XPhos (2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl) (10 mol%) and DMSO (2 mL). The vessel was sealed and heated at 120 C (oil bath temperature) for 24 h and then cooled to room temperature. The reaction mixture was washed withs aturated Na2S2O3 (2 × 15 mL) and then brine (15 mL). After the aqueous layer had been extracted with EtOAc, the combined organic layers were dried over anhydrous Na2SO4 and evaporated under vacuum. The residue was purified by flash column chromatography (hexane/EtOAc) to afford the product 3a. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 83% | With tert.-butylhydroperoxide; potassium carbonate; In water; at 100℃; for 2h; | General procedure: In a typical run, a mixture of diphenyl disulfide (0.2 mmol), p-tolualdehyde (2.0 mmol), K2CO3(0.4 mmol), tert-butyl hydroper-oxide (TBHP) (0.6 mmol), catalyst (40 mg), H2O (2.0 mL) was stirredat desired temperature for 2 h. After the reaction was completed,the mixture was cooled down to room temperature and thenextracted with ethyl acetate. The organic phase was analyzed on anAgilent 7890A GC equipped with a FID detector and mass spectrom-eter. The product was purified by column chromatography on silicagel (200?300 mesh) (eluent: petroleum ether and ethyl acetate).The obtained product was identified by NMR spectra using a Bruker500 MHz spectrometer instrument. The1H NMR (500 MHz) and13CNMR (125 MHz) were recorded with spectrometers at 20C usingCDCl3as the solvent. Chemical shifts are given in parts per millionrelative to TMS as the internal standard at room temperature. Thespectra data were consistent with authentic compounds. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 77% | With sodium iodide; In acetonitrile; at 20℃; for 18h;Irradiation; | General procedure: To a 20 mL glass tube with a stir bar was charged 2-methyl-1H-indole 1a (39.35 mg, 0.3 mmol), diphenyldisulfide 2a (65.50 mg, 0.3 mmol), NaI (0.06 mmol, 9 mg) and MeCN (2 mL). The solution was stirred at room temperature with the irradiation of a 12 W blue LED for 18 h. The solvent was removed under vacuum. The residue was purified by column chromatography over silica gel (petroleum ether/ethyl acetate = 15/1) to give the product 3a (60 mg, 83%). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 74% | With sodium iodide; In acetonitrile; at 20℃; for 18h;Irradiation; | General procedure: To a 20 mL glass tube with a stir bar was charged 2-methyl-1H-indole 1a (39.35 mg, 0.3 mmol), diphenyldisulfide 2a (65.50 mg, 0.3 mmol), NaI (0.06 mmol, 9 mg) and MeCN (2 mL). The solution was stirred at room temperature with the irradiation of a 12 W blue LED for 18 h. The solvent was removed under vacuum. The residue was purified by column chromatography over silica gel (petroleum ether/ethyl acetate = 15/1) to give the product 3a (60 mg, 83percent). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With n-butyllithium; In tetrahydrofuran; for 0.5h;Cooling with ice; | A mixed solution of NBS (N-bromosuccinimide) / THF was added dropwise to a reaction flask equipped with 1 mol of A,In the nitrogen protection conditions heated to 40C for 1 hour, the bromination reaction to be B.then,JoinDibenzo-substituted disulfideDiphenyl disulfide compound Ph-S-S-Ph,The compound C was obtained by sufficiently stirring for half an hour with n-BuLi / THF as a catalyst in a low-temperature dry ice bath.Finally, a mixed solution of meta-chlorobenzoic acid mCPBA / CH2Cl2 was introduced, and the mixture was stirred for 1 hour,Add water, precipitate solid,Followed by recrystallization using n-hexane and ethanol to obtain SDF-DPSO2 in a yield of 38percent. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 52% | With copper diacetate; potassium hydroxide; In toluene; at 130℃; for 48h;Schlenk technique; | 1) Take 0.25mmol of 6-methoxyquinoline nitrogen oxide,diphenyl disulfide 0.45mmol,Cu(AcO)20.125mmol,and potassium hydroxide 0.5mmol,add 1 mL of toluene to make a mixture,the mixture was placed in a 5 ml schlenk tube.after heating in an oil bath at 130 C for 48 hours, the reaction solution was cooled to room temperature. 2) Concentrate the reaction solution to obtain a concentrate, and use a mixed solvent consisting of ethyl acetate and petroleum ether in a volume ratio of 1:1 as a developing agent and silica gel as an adsorbent to perform thin layer chromatography to obtain a target of 38 mg product. The target product yield of this example was 52% and the target product was subjected to nuclear magnetic characterization. |