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Structure of 103-19-5
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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.
4.5
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Synthesis of N-Sulfenylimines from Disulfides and Primary Methanamines
Robert Kawȩcki ;
Abstract: N-Sulfenylimines (sulfenimines, thiooximes, N-alkylidenesulfenamides) were efficiently synthesized through the reaction of primary amines and disulfides with NBS or bromine. This reaction can be carried out in an open flask at room temperature without the need for any transition-metal-containing additives. The use of thiols instead of disulfides gave similar results. A wide range of amines were reacted with aryl and alkyldisulfides, resulting in the formation of sulfenimines in a yield of 44–99%.
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| CAS No. : | 103-19-5 |
| Formula : | C14H14S2 |
| M.W : | 246.39 |
| SMILES Code : | CC1=CC=C(SSC2=CC=C(C)C=C2)C=C1 |
| English Name : | p-Tolyl disulfide |
| MDL No. : | MFCD00008547 |
| InChI Key : | TZOVOULUMXXLOJ-UHFFFAOYSA-N |
| Pubchem ID : | 66027 |
| GHS Pictogram: | |
| Signal Word: | |
| Hazard Statements: | |
| Precautionary Statements: | |
| Class: | |
| UN#: | |
| Packing Group: |
| Num. heavy atoms | 16 |
| Num. arom. heavy atoms | 12 |
| Fraction Csp3 | 0.14 |
| Num. rotatable bonds | 3 |
| Num. H-bond acceptors | 0.0 |
| Num. H-bond donors | 0.0 |
| Molar Refractivity | 74.53 |
| TPSA ? Topological Polar Surface Area: Calculated from |
50.6 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.32 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
5.14 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
5.1 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
4.95 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
4.66 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
4.64 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-4.96 |
| Solubility | 0.00268 mg/ml ; 0.0000109 mol/l |
| Class? Solubility class: Log S scale |
Moderately soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-5.95 |
| Solubility | 0.000278 mg/ml ; 0.00000113 mol/l |
| Class? Solubility class: Log S scale |
Moderately soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-5.92 |
| Solubility | 0.000299 mg/ml ; 0.00000121 mol/l |
| Class? Solubility class: Log S scale |
Moderately soluble |
| GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
| BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
| P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
| CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
| CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
Yes |
| CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
Yes |
| CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
| CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
| Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-4.15 cm/s |
| Lipinski? Lipinski (Pfizer) filter: implemented from |
1.0 |
| Ghose? Ghose filter: implemented from |
None |
| Veber? Veber (GSK) filter: implemented from |
0.0 |
| Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
| Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
| Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
| PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
| Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
| Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<2.0 |
| Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.28 |
* 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 |
|---|---|---|
| 54% | With phosphorus pentoxide; tetra-(n-butyl)ammonium iodide; potassium iodide In sulfolane at 93℃; for 12h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 88% | With piperidinium thiotungstate In N,N-dimethyl-formamide for 12h; Ambient temperature; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 1: 72% 2: 21% 3: 4% | In carbon disulfide for 40h; Ambient temperature; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With sodium p-thiocresolate In ethanol |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 25% | With para-thiocresol In methanol Ambient temperature; Yields of byproduct given; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 51% | In sulfolane at 230℃; for 0.166667h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 12% | With sodium hydride 2.) MeCN, irradiation; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 21% | With triethylamine In diethyl ether |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 33% | With diisobutylaluminium hydride In tetrahydrofuran; methanol; toluene at -78 - 20℃; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 44% | With diisobutylaluminium hydride In tetrahydrofuran; methanol; toluene at -78 - 20℃; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 45% | With diisobutylaluminium hydride In tetrahydrofuran; methanol; toluene at -78 - 20℃; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 82% | Stage #1: di(p-tolyl) disulfide With aluminium trichloride; zinc In acetonitrile at 80℃; for 2h; Stage #2: diphenyliodonium iodide In water; acetonitrile at 80℃; for 4h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 91% | Stage #1: di(p-tolyl) disulfide With samarium diiodide In tetrahydrofuran at 20℃; Stage #2: (E)-1-(1H-benzo[d][1,2,3]triazol-1-yl)-3-phenylprop-2-en-1-one In tetrahydrofuran at 20℃; for 0.5h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 3 steps 1: concentrated hydriodic acid; sulfuric acid; water 2: p-tolyl mercaptan; alcohol 3: NaOH-solution | ||
| Multi-step reaction with 3 steps 1: concentrated hydriodic acid; sulfuric acid; water 2: p-tolyl mercaptan; alcohol 3: natrium carbonate; NaOH-solution |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 94% | With tributylphosphine In tetrahydrofuran at 80℃; for 22h; | 19.1 (Example 19) In Example 19, ( 2S,4R)-4-(4-methylphenylthio)pyrrolidine-2-carboxylate ( IVa ) was synthesized by the method shown below. 1) Coupling Step [Show Image] To a solution of methyl(2S,4S)-1-tert-butoxycarbonyl-4-hydroxypyrrolidine-2-carboxylate (40.3 mg, 164 µ mol) in THF ( 1 mL ) , di-p-tolyl disulfide ( 124 mg, 503 µ mol ) and tributylphosphine ( 123 µ L, 494 µ mol ) were added under the argon atmosphere, and the reaction solution was stirred at 80°C for 22 hours. To the reaction mixture, after cooled down to room temperature, water was added, and the product was extracted with ethyl acetate and concentrated in vacuo, and the residue was purified by column chromatography (silica gel 60, hexane/ethyl acetate=4/1) to obtain the coupling product described above (54.0 mg, 94%). TLC and 1H NMR data are shown below. TLC: Rf = 0.30 (silica gel , hexane / ethyl acetate = 4 / 1 ) 1H NMR ( 400 MHz, CDCl3): ( two rotamers ) δ ( ppm ) 1.40 and 1.45 (s, 9H), 2.15-2.30 (m, 2H), 2.34 and 2.35 (s, 3H), 3.36 (dd, J = 6.5 and 10.8 Hz) and 3.44 (dd, J = 6.3 and 11.1 Hz) (1H), 3.68-3.77 (complex, 1H), 3.72 and 3.72 (s, 3H), 3.83 (dd, J = 6.8 and 10.8 Hz) and 3.87 (dd, J = 6.7 and 11.1 Hz) (1H), 4.34 (t, J = 6.6 Hz) and 4.43 (dd, J = 4.6 and 8.1 Hz) (1H), 7.12 (d, J = 7.8 Hz) and 7.14 (d, J = 7.8 Hz) (2H), 7.32 (d, J = 7.8 Hz, 2H). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 68% | With rongalite; potassium carbonate In N,N-dimethyl-formamide at 20℃; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 78% | With copper(l) iodide; caesium carbonate In dimethyl sulfoxide at 80℃; for 4h; chemoselective reaction; | General procedure for synthesis of 3-chalcogenylindoles: 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. |
| 59% | With iodine In toluene at 110℃; for 10h; Schlenk technique; | |
| 67 % | With potassium <i>tert</i>-butylate In dimethyl sulfoxide at 120℃; Schlenk technique; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 82% | 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 |
|---|---|---|
| With tributylphosphine In tetrahydrofuran at 20℃; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 83% | 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 |
|---|---|---|
| 73% | With sodium dithionite; potassium carbonate In water; dimethyl sulfoxide at 60℃; | 4.2. General procedure for the synthesis of S-aryl 2-aminobenzothioates 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 |
|---|---|---|
| 24% | Stage #1: 6-methyl-1H-indole-2-carboxylic acid With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.25h; Stage #2: di(p-tolyl) disulfide In N,N-dimethyl-formamide; mineral oil at 50℃; for 24h; Inert atmosphere; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 72% | With potassium iodide; In dichloromethane; at 20℃; | 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. m-Vinylbenzaldehyde (1k) (67 mg, 0.50 mmol). Column chromatography (silica gel; 2-8% EtOAc/hexanes) yields 3kd (115 mg, 72%); light yellow viscous oil; Rf (10% EtOAc/hexanes) 0.36; IR (neat): νmax 1744, 1699, 1230 cm-1; 1H NMR (300 MHz, CDCl3): δ 9.97 (s, 1 H, CHO), 7.84-7.76 (m, 2H, ArH), 7.57 (dt, J=7.6, 1.5 Hz, 1H, ArH), 7.48 (t, J=7.6 Hz, 1H, ArH), 7.27 (br d, J=8.0 Hz, 2H, ArH), 7.08 (br d, J=8.0 Hz, 2H, ArH), 5.90 (dd, J=7.5, 5.9 Hz, 1H, ArCH), 3.38 (dd, J=14.0, 7.5 Hz 1H, CHH), 3.20 (dd, J=14.0, 5.9 Hz 1H, CHH), 2.30 (s, 3H, CH3), 2.04 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3): δ 191.6, 169.7, 140.1, 136.9, 136.5, 132.7, 131.2, 131.0, 129.7, 129.6, 129.1, 127.5, 73.9, 40.4, 20.9, 20.8; HRMS (ESI-TOF): MNa+, found: 337.0875; error=0.2 ppm requires C18H18NaO3S 337.0874. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 85% | With sodium hypochlorite pentahydrate; acetic acid; sodium bromide for 1.33333h; | 3 In an eggplant type flask, sodium hypochlorite pentahydrate1.06 g (6.4 mmol),0.82 g (8.0 mmol) of sodium bromide, and 8 mL of acetic acid,And the mixture was stirred under warming for 20 minutes. after that,0.246 g (1.0 mmol) of the raw material di-p-tolyl disulfide was added and reacted for 80 minutes with stirring after completion of the raw material addition.After completion of the reaction, 50 mL of water was added to the obtained reaction mixture, salts in the reaction mixture were dissolved in an aqueous phase, then extracted with chloroform three times, anhydrous magnesium sulfate was added to the organic phase, dried, dried, After that, the solvent was distilled off,0.473 g (1.7 mmol, yield: 85%) of p-tolylsulfonyl bromide as a reaction product was obtained. |
| 85% | With sodium hypochlorite pentahydrate; sodium bromide In acetic acid at 20℃; for 1.33333h; | Standard Procedure for the Synthesis of Sulfonyl Bromides 4 from Disulfides 1 or Thiols 2 (Tables 8 and 9) General procedure: To a solution of NaBr (823 mg, 8.0 mmol) in acetic acid (7 mL), NaOCl·5H2O (1.07 g, 6.5 mmol) was added under stirring, and the resulting mixture was stirred at room temperature for another 30 min. A solution of disulfide (1) or thiol (2) (1.0 mmol) in AcOH (1 mL) was then added to the mixture under stirring. The reaction was monitored by TLC and stirring was continued until the starting material disappeared. H2O (50 mL) was added to the reaction mixture, which was then extracted with chloroform (3 × 5 mL). The combined extract was dried (anhyd MgSO4) and evaporated to obtain the corresponding sulfonyl bromide 4. The product was analyzed without further purification. 4-Toluenesulfonyl Bromide (4a)12 Yield: 85% (from disulfide), 91% (from thiol); colorless crystals; mp 95 °C (Lit.22b mp 95-96 °). 1H NMR (CDCl3): δ = 7.89 (2 H, d, J = 8.4 Hz), 7.39 (2 H, d, J = 8.4 Hz), 2.49 (3 H, s). 13C NMR (CDCl3): δ = 146.9, 144.6, 130.1, 126.5, 21.9. |
| 79% | With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione In water; acetonitrile at 20℃; for 3h; |
| 76% | With ammonium nitrate; hydrogen bromide; oxygen In water; acetonitrile at 60℃; for 3h; Green chemistry; | |
| 62% | With N-Bromosuccinimide In water; acetonitrile at 20℃; for 6h; Inert atmosphere; Darkness; | |
| 40% | With nickel(II) triflate; potassium hydrogen difluoride; dihydrogen peroxide; copper(l) cyanide; potassium bromide In water; acetonitrile at 0 - 25℃; for 18h; Schlenk technique; Inert atmosphere; | |
| With methanol; N-Bromosuccinimide In dichloromethane at 20℃; for 0.25h; |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 83% | With iodine In tetrahydrofuran at 80℃; for 12h; | Synthesis of 3a General procedure: 2,3-dihydro-6-phenylimidazo[2,1-b]thiazole 1a (101mg, 0.5 mmol), 1,2-diphenyldisulfane (109mg, 0.5 mmol), and I2 (152 mg, 0.6 mmol) were stirred in 2 mL of THFat 80 °C for 12 h. The reaction was quenched by addition of sat. aq. Na2S2O3(8 mL). The aqueous solution was extracted with ethyl acetate (3×8 mL) and the combined extract was dried with anhydrous MgSO4. The solvent was removed and the crude product was separated by column chromatography (eluted with petroleum ether/ethyl acetate = 4:1) to give a pure sample of 3a |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 86% | With ammonium iodide In N,N-dimethyl acetamide at 135℃; for 12h; regioselective reaction; | 2 General procedure for the synthesis of 3-sulfanyl-chromones 3 General procedure: 0.5 mL DMAC was added into the flask charged with 0.25 mmol of flavones, 0.25 mmol of diaryl disulfides, NH4I (1 mmol). The mixture was stirred at 135 °C for 12 hours, then cooled down to room temperature, diluted with 20 mL ethyl acetate and washed with 10 mL H2O. The aqueous layer was extracted twice with ethyl acetate (5 mL) and the combined organic phase was dried over Na2SO4. After evaporation of the solvents the residue was purified by flash column chromatography (silica gel, PE/EtOAc=5:1) to afford the desired products 3. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 95% | With silver hexafluoroantimonate In 1,2-dichloro-ethane at 110℃; for 8h; | |
| 95% | With silver hexafluoroantimonate In 1,2-dichloro-ethane at 90℃; for 10h; High pressure; | 19 Example 19 7-chloroisoquinolin-1 (2Η)-one (12 mmol), bis(4-methylphenyl) disulfide (10 mmol), hexafluoride was sequentially added to a pressure-resistant reaction tube at room temperature. Silver acetate (10 mmol) and dichloroethene (6 mL). The reaction mixture was then reacted at 90 ° C for 10 hours. The reaction was stopped, concentrated under reduced pressure to give a crude material, which was washed with a mixture of petroleum ether and ethyl acetate. 4-(4-Methylphenylthio)-7-chloroisoquinolin-1 (2H)-one. Yield 95%; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 85% | With silver hexafluoroantimonate In 1,2-dichloro-ethane at 110℃; for 8h; | |
| 85% | With silver hexafluoroantimonate In 1,2-dichloro-ethane at 110℃; for 10h; High pressure; | 22 Example 22 5-methylisoquinolin-1 (2Η)-one (12mm0l), bis(4-methylphenyl)disulfide (llmmol), hexafluorofluoride was sequentially added to the pressure-resistant reaction tube at room temperature. Silver citrate (15mm0l) and dichloroethane (9mL). The reaction mixture was then reacted at 110 ° C for 10 hours. The reaction was stopped, concentrated under reduced pressure to give a crude material, which was washed with a mixture of petroleum ether and ethyl acetate. 4-(4-Methylphenylthio)-7-chloroisoquinolin-1 (2H)-one. Yield 85% |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 86% | With dipotassium peroxodisulfate; copper(II) bis(trifluoromethanesulfonate) In acetonitrile at 60℃; regioselective reaction; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 70% | With dipotassium peroxodisulfate; copper(II) bis(trifluoromethanesulfonate) In acetonitrile at 60℃; regioselective reaction; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 70% | With dipotassium peroxodisulfate; lithium chloride In acetonitrile at 70℃; regioselective reaction; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 76% | With rhodium(III) chloride trihydrate; copper diacetate; tris(2,6-dimethoxyphenyl)phosphine In N,N-dimethyl-formamide at 120℃; for 6h; regioselective reaction; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 35% | With rhodium(III) chloride trihydrate; copper diacetate; tris(2,6-dimethoxyphenyl)phosphine In N,N-dimethyl-formamide at 120℃; for 12h; regioselective reaction; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 96% | With bis-[(trifluoroacetoxy)iodo]benzene In dichloromethane at 20℃; for 0.5h; regioselective reaction; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 80% | With palladium diacetate; caesium carbonate; triphenylphosphine; zinc In water; N,N-dimethyl-formamide at 80℃; for 12h; | 2 23.8 mg (0.1 mmol) (1-bromo-2,2,2-trifluoroethyl)benzene, 12.3 mg (0.05 mmol) bis(p-tolyl) disulfide, 2.2 mg (0.01 mmol) palladium acetate, 26.2 mg (0.1 mmol) triphenylphosphine, 42.4 mg (0.15 mmol) cesium carbonate, 13.0 mg (0.2 mmol) of zinc powder and 14.4 mg (0.8 mmol) of deionized water were added to 2 ml of solvent N,N-dimethylformamide. The reaction was stirred at 80 °C for 12 hours. After the reaction was completed, it was cooled, the mixture was poured into ethyl acetate, and washed with saturated brine (2×15 mL). After extracting the aqueous layer with ethyl acetate, the combined organic layer was dried with anhydrous Na2SO4, filtered and the filtrate was removed from the solvent with a rotary evaporator to obtain the residue. The residue was subjected to column layer separation through a silica gel column and passed through the eluent After washing, the effluent containing the target product is collected, the effluents are combined and concentrated in vacuo to remove the solvent to obtain the target product. The residue is eluted with petroleum ether eluent through a silica gel column, and the effluent is collected according to the actual gradient. TLC detection, combined the effluent containing the product, the rotary evaporator distilled off the solvent, vacuum dried to obtain a colorless liquid, (1-fluoro-2-phenylvinyl) (4-methylphenyl) sulfide 19.5 mg, yield Rate 80% |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 46 % | With tert-butylammonium hexafluorophosphate(V); potassium iodide In acetonitrile at 20℃; Electrochemical reaction; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 46 % | With tert-butylammonium hexafluorophosphate(V); potassium iodide In acetonitrile at 20℃; Electrochemical reaction; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Stage #1: di(p-tolyl) disulfide With 1,10-Phenanthroline; triethylamine hydrochloride; nickel dichloride; zinc In toluene at 20℃; Schlenk technique; Inert atmosphere; Stage #2: methyl 3,3,3-trifluoropropionate With chloro-trimethyl-silane In N,N-dimethyl-formamide; toluene at 80℃; Schlenk technique; Inert atmosphere; Overall yield = 71 percent; Overall yield = 29.58 mg; Optical yield = 50 percent de; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 76 % | With tris(2,2-bipyridine)ruthenium(II) hexafluorophosphate; diisopropyl-carbodiimide In N,N-dimethyl acetamide at 20℃; Schlenk technique; Inert atmosphere; Irradiation; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 77% | With tetra-N-butylammonium tribromide In dimethyl sulfoxide at 50℃; for 12h; | 4.2. TBATB-promoted reaction procedure of pyrrolo [1,2-a]quinoxalinewith diaryl disulfides General procedure: A 10 mL thick-walled pressure-resistant tube was charged withpyrrolo[1,2-a]quinoxaline (1, 0.2 mmol), TBATB (0.1 mmol), diaryldisulfide (2, 0.1 mmol) and dimethyl sulfoxide (DMSO, 2 mL). Themixture was stirred at 50 C for 12 h. Once the reaction had reachedcompletion, the solution was quenched with a saturated solution of sodium thiosulfate (10 mL) and extracted with ethyl acetate (15 mL ×3). The organic layer was then dried with anhydrous Na2SO4 and the solvent was removed under reduced pressure. The crude product was purified by rapid chromatography on silica gel (petroleum ether/ethyl acetate =10:1) to yield the final products 4a-4v. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 72% | With tetra-N-butylammonium tribromide In dimethyl sulfoxide at 100℃; for 12h; | 4.3.Involvement of TBATB in the three-component reaction of pyrrolo [1,2-a]quinoxaline with diaryl disulfide General procedure: A 10 mL thick-walled pressure-resistant tube was charged with pyrrolo[1,2-a]quinoxaline (1, 0.2 mmol), TBATB (0.12 mmol), diaryl disulfide (2, 0.12 mmol) and dimethyl sulfoxide (DMSO, 2 mL). The mixture was stirred at 100 C for 12 h. Once the reaction had reached completion, the solution was quenched with a saturated solution of sodium thiosulfate (10 mL) and extracted with ethyl acetate (15 mL ×3). The organic layer was dried with anhydrous Na2SO4 and the solvent was removed under reduced pressure. The residue was purified from the crude product by rapid chromatography on silica gel (petroleum ether/ ethyl acetate =10:1) to yield the final products 5a-5t. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 92% | at 70℃; for 3h; | 40 Synthesize (4l) from p-methylphenyl disulfide (1b) and bis(p-trifluoromethylphenyl)phosphine oxide (2e): 0.3 mmol of p-methylphenyl disulfide (1b) and 0.3 mmol of bis(p-trifluoromethylphenyl)phosphine oxide (2e) were added to the reaction flask and reacted at 70°C until the raw materials disappeared completely. Dichloromethane and saturated sodium carbonate aqueous solution were added for extraction three times, and the organic phases were combined and dried to obtain a white powder with a yield of 92%. |
| 92% | In neat (no solvent) at 70℃; for 3h; Sealed tube; Green chemistry; | Experimental Procedure. General procedure: Disulfide 1 (0.3 mmol, 1.0 equiv.) and P(O)H compound 2 (0.3 mmol, 1.0 equiv.) were added to a 4 mL sealed tube and the mixture was then stirred at the corresponding temperature in air for several hours. The reaction was monitored by TLC. After completion of the reaction, DCM (10 mL) was added and the mixture was washed with saturated Na2CO3 solution (3 × 10 mL). During this weak alkali wash process, mercaptan was removed and recovered efficiently. The combined organic layer was dried over anhydrous Na2SO4 and concentrated by vacuum. In most cases, the products were obtained without any further purification. In some cases, the residues were purified by flash column chromatography on silica gel to provide the corresponding product with good to excellent yields. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 99% | at 70℃; for 3h; | 42 Synthesis (4n) from p-methylphenyl disulfide (1b) and bis(3,5-di-tert-butylphenyl)phosphine oxide (2q): 0.3 mmol of p-methylphenyl disulfide (1b) and 0.3 mmol of bis(3,5-di-tert-butylphenyl)phosphine oxide (2q) were added to a reaction flask and reacted at 70°C until the raw materials disappeared completely. Dichloromethane and saturated sodium carbonate aqueous solution were added for extraction three times, and the organic phases were combined and dried to obtain a white solid with a yield of 99%. |
| In neat (no solvent) at 70℃; for 3h; Sealed tube; Green chemistry; | Experimental Procedure. General procedure: Disulfide 1 (0.3 mmol, 1.0 equiv.) and P(O)H compound 2 (0.3 mmol, 1.0 equiv.) were added to a 4 mL sealed tube and the mixture was then stirred at the corresponding temperature in air for several hours. The reaction was monitored by TLC. After completion of the reaction, DCM (10 mL) was added and the mixture was washed with saturated Na2CO3 solution (3 × 10 mL). During this weak alkali wash process, mercaptan was removed and recovered efficiently. The combined organic layer was dried over anhydrous Na2SO4 and concentrated by vacuum. In most cases, the products were obtained without any further purification. In some cases, the residues were purified by flash column chromatography on silica gel to provide the corresponding product with good to excellent yields. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 98% | at 70℃; for 3h; | 41 Synthesized from p-methylphenyl disulfide (1b) and 1,1-dinaphthylphosphine oxide (2u) (4m): 0.3 mmol of p-methylphenyl disulfide (1b) and 0.3 mmol of 1,1-dinaphthylphosphine oxide (2u) were added to the reaction flask and reacted at 70°C until the raw materials disappeared completely. Dichloromethane and saturated sodium carbonate aqueous solution were added for extraction three times, and the organic phases were combined and dried to obtain a white powder with a yield of 98%. |
| 98% | In neat (no solvent) at 70℃; for 3h; Sealed tube; Green chemistry; | Experimental Procedure. General procedure: Disulfide 1 (0.3 mmol, 1.0 equiv.) and P(O)H compound 2 (0.3 mmol, 1.0 equiv.) were added to a 4 mL sealed tube and the mixture was then stirred at the corresponding temperature in air for several hours. The reaction was monitored by TLC. After completion of the reaction, DCM (10 mL) was added and the mixture was washed with saturated Na2CO3 solution (3 × 10 mL). During this weak alkali wash process, mercaptan was removed and recovered efficiently. The combined organic layer was dried over anhydrous Na2SO4 and concentrated by vacuum. In most cases, the products were obtained without any further purification. In some cases, the residues were purified by flash column chromatography on silica gel to provide the corresponding product with good to excellent yields. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 75% | With 4CzIPN; 2-tert-butyl-1,1,3,3-tetramethylguanidine In dichloromethane at 20℃; Irradiation; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 1: 75% 2: 18% | With 4CzIPN; 2-tert-butyl-1,1,3,3-tetramethylguanidine In dichloromethane at 20℃; Irradiation; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 42% | With iodine In dimethyl sulfoxide at 120℃; for 24h; Sealed tube; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 88% | In acetonitrile at 80℃; for 6h; Schlenk technique; Inert atmosphere; Green chemistry; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 1: 1.3% 2: 1.7% 3: 2.3% | With zinc(II) chloride In dimethyl sulfoxide at 20℃; for 10h; Irradiation; Inert atmosphere; Schlenk technique; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 93% | In dichloromethane at 60℃; for 6h; | 11 Example 11 Azobisisobutyronitrile (248 mg, 1 mmol), [1.1.1]spiropropane (66 mg, 1 mmol), and p-toluene disulfide (246 mg, 1 mmol) were added to a reaction flask. Dichloromethane (20 g) was added to dissolve the precipitate, and the mixture was stirred at 60°C for 6 hours.After the reaction was complete, saturated sodium bicarbonate aqueous solution (20 g) was added to quench the reaction. Dichloromethane (20 g) was then added, and the mixture was stirred thoroughly and allowed to stand for separation. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated to obtain a brown crude product. The crude product was purified by silica gel column chromatography (ethyl acetate/petroleum ether = 1:80) to obtain 272 mg of a deep yellow solid, with a yield of 93% and a melting point of 87°C. |
Tags: 103-19-5 | p-Tolyl disulfide | Aryls | Sulfides | Benzene Compounds | Organic Building Blocks
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