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CAS No. : | 6320-01-0 | MDL No. : | MFCD00009603 |
Formula : | C6H5BrS | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | HNGQQUDFJDROPY-UHFFFAOYSA-N |
M.W : | 189.07 | Pubchem ID : | 80597 |
Synonyms : |
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Signal Word: | Danger | Class: | 9 |
Precautionary Statements: | P261-P264-P273-P301+P310-P302+P352-P305+P351+P338 | UN#: | 3335 |
Hazard Statements: | H301-H315-H319-H335-H410 | 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 |
---|---|---|
100% | With iodine In lithium hydroxide monohydrate; acetonitrile at 25℃; | 36.1 Production of (3-bromophenyl)(trifluoromethyl)sulfane Step 1: To a solution of 3-bromobenzenethiol (1.89 g, 10 mmol, 1.0 equiv) in a liquid mixture of water and acetonitrile (water:acetonitrile = 1:5, 30 mL) was added iodine (1.27 g, 5 mmol, 0.5 equiv) at room temperature, and the reaction was immediately completed. A saturated Na2S2O3 aqueous solution was added thereto, and organic compounds were extracted with CH2Cl2. The combined organic layer was dried over Na2SO4, filtered, and concentrated in vacuo to give 1,2-bis(3-bromophenyl)disulfane as a colorless solid (1.9 g, 100% yield) (). 1H NMR (400 MHz, CDCl3) δ 7.62 (2H, s), 7.35-7.40 (4H, m), 7.14-7.19 (2H, m). |
91% | With pyridinium chlorochromate In dichloromethane at 0 - 20℃; for 1h; | 1c; 24.24c The sufinic methyl ester used in Example Ia was generated by the oxidation of an aryl thiol, first with PCC (Salehi, P. et al, Synthetic Communications, 31(IS), 2777-2781 (2001)), and then with bromine. A solution of a bromine substituted benzenethiol is treated with pyridnium chlorochromate to give bis-bromophenyldisulfide. Oxidation with bromine in methanol (Resek, J. E. et al, Tetrahedron Lett. 36, 7051-7054 (1995)), followed by aqueous workup, gives bromo-benzenesulfinic acid methyl ester. It is EPO recognized, by those skilled in the art, that different aryl thiols may be used, such as phenyl, naphthyl, pyridyl, imidazolyl, thiazolyl, furanyl, thienyl, benzothiazolyl, pyrazolyl, pyrimidinyl, benzimidazolyl, benzofuranyl, indolyl, or benzothiop^enyl any of which is optionally substituted. EXAMPLE 24c: bis-3-Bromophenyldisulfide EPO Pyridinium chlorochromate (Aldrich, 11.2 g, 51.96 mmol) was added portionwise to a 0 0C solution of 3-bromo-benzenethiol (Aldrich, 6.14 mL, 51.92 mmol) in CH2Cl2 (100 mL). The reaction was stirred at room temperature for 1 hour and then quenched with silica gel for 10 minutes. The slurry was filtered through Celite, which was subsequently washed with hexanes (250 mL). The filtrate was concentrated in vacuo to afford the title compound as a brown oil (8.9 g, 91% yield). |
86% | With Bromotrichloromethane In tetrahydrofuran at 20℃; for 12h; Schlenk technique; Irradiation; | 8 Example 8 Add 75.8mg (0.4mmol) of meta-bromothiophenol and 237.9mg (1.2mmol) of bromotrichloromethane into a 10mL Schlenk container, and then add 2mL of tetrahydrofuran with a syringe, and react for 12h under the irradiation of a 23W energy-saving lamp at room temperature. After the reaction is complete After concentrating to remove the solvent, the crude product was separated by silica gel column chromatography (eluent: petroleum ether) to obtain a colorless liquid: 64.3 mg, yield: 86%. |
86% | With Bromotrichloromethane In tetrahydrofuran at 20℃; Irradiation; | |
81% | With iodine In lithium hydroxide monohydrate; acetonitrile at 25℃; | 5) General Procedure for the Synthesis of Disulfides 5a-5m. General procedure: A round bottom flask equipped with magnetic stirrer is charged with thiophenol S10 (10 mmol, 1.0 equiv.) and a mixture of water-acetonitrile (w : a = 1 : 5, 30 mL). Then to the stirring solution, iodine (5 mmol, 0.5 equiv.) was added at room temperature. Completion of the reaction was monitored by TLC. After that, a solution of 1% aqueous Na2S2O3 (30 mL) was added and the mixture was stirred on to decolourisation of brown-yellow reaction mixture. The mixture was then extracted with CH2Cl2 (3×40 mL) and dried over anhydrous Na2SO4. The organic solution was evaporated to dryness and the residue was chromatographed on a short column of silica gel using PE as eluent. The pure diphenyl disulfide (5a-5m) was obtained as colourless crystals. |
59.3% | With boron trifluoride diethyl ether complex; silver(I) nitrate In acetonitrile at 20℃; for 24h; | 4.2. General procedure using AgNO3 / BF3 · OEt2/ ACN (dry) (System A) General procedure: 7 mmol of halogenated thiol was dissolved in anhydrous ACN(23 mL). Then, 7.7 mmol of AgNO3 and 0.8 mL of BF3O(Et)2 wereadded dropwise to the reaction mixture. The mixture was stirred andmonitored at intervals by TLC chromatography (hexane / EtOAc 9:1).After 24 h, the reaction was stopped and treated with ice. After extractionwith ethyl acetate, the organic layer was washed with distilledwater and brine and dried over MgSO4, followed by filtration underreduced pressure. The products were purified by silica gel (GF DE500 μm, UNIPLAT) chromatography using hexane/EtOAc (9:1) as theeluent. |
With ethanol; iodine | ||
With sodium hydroxide; dihydrogen peroxide | ||
Stage #1: 3-bromobenzenethiol With sodium hydroxide In lithium hydroxide monohydrate for 0.5h; Inert atmosphere; Stage #2: With potassium hexacyanoferrate(III) In lithium hydroxide monohydrate at 20℃; for 14h; Inert atmosphere; | ||
With iodine; dimethyl sulfoxide | ||
With aluminum-based organometallic framework In acetonitrile at 20℃; for 6h; Sonication; | 14 Example 1 General procedure: The present embodiment provides a method for preparing diphenyl disulfide compounds by heterogeneous catalysis, comprising the following steps:(a) 50 mg of aluminum-based organometallic framework catalyst (The synthesis of aluminum-based organometallic framework catalysts is as follows: 133mg green rate and 166mg terephthalic acid dispersed in 5mLN,N-dimethylformamide (DMF), magnetic stirring at room temperature for 30min,After magnetic stirring to a transparent solution, transfer to a polytetrafluoroethylene autoclave,In an oven at 150°C for 12h. After natural cooling, the obtained samples were centrifuged and washed three times with DMF, methanol, and deionized water, respectively. Finally, place the obtained orange powder in a vacuum drying oven at 120°C for 24h), after mixing 1mmol of thiophenol and acetonitrile organic solution uniformly, ultrasonically (electric power 80W) to disperse for 10min to obtain a suspension; (b) pass the dispersed suspension into air, and stir and react at room temperature for 0.5h;(c) drying and concentrating the organic phase obtained in step (b) to obtain diphenyl disulfide. Through gas chromatograph testing and analysis, the conversion rate of thiophenol is 99%, and the diphenyl disulfide selectivity is 91%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80.7% | With potassium carbonate In dimethyl sulfoxide at 90℃; for 12h; | 1 A compound of formula A (20.0 g, 127.4 mmol) and formula B (24.0 g, 127.4 mmol) was dissolved in DMSO (200 mL), and potassium carbonate (26.4 g, 191.1 mmol) was added and stirred at 90 °C. After 12 hours, water (200 ml) was added and the solid obtained by filtration was washed with water and ethanol to prepare a compound of Formula C (31.8 g, yield 80.7%). |
With potassium hydroxide | ||
With ethanol; sodium carbonate |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With potassium carbonate; potassium iodide In acetone at 65℃; for 5h; | 4.1 1. Synthesis of 4-cyanobenzyl-3-bromophenyl sulfide In a 250 mL three-necked flask containing a magnetic rotor, 3-bromothiophenol (18.90 g, 0.10 mol), 4-cyanobenzyl bromide (19.60 g, 0.10 mol), and potassium carbonate (27.64 g, 0.2 mol) were added successively. The catalyst potassium iodide (0.5 g) and the solvent acetone (90 mL) were heated to 65 ° C to stir and reflux. After the end of the reaction, the product was slowly added to a stirred 10-fold volume of distilled water, and the precipitate was collected by filtration and recrystallized from ethanol to give a product (yield: 79%). |
(i) NaOEt, EtOH, (ii) /BRN= 636717/; Multistep reaction; | ||
With potassium carbonate In acetone at 80℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With piperidine In 1,4-dioxane for 3h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium hydroxide In water; dimethyl sulfoxide at 20℃; for 120h; | 17.1 To a stirred solution of 3-bromothiophenol (5,0 g, 26 mraol) in DMSO (40 mL) was added a solution of KOH pellets (85% by wt, 2.15 g, 32 mmol) in water (4 inL) followed by bromoacetaldehyde diethyl acetal (4.5 mL, 29 mmol). The mixture was stirred at rt for 5 d, diluted with ether (300 mL) and washed with water (3 x 100 mL). The combined water washes were extracted with ether (100 mL). The combined ether extracts were washed with brine (100 mL), dried over MgSO4 and concentrated to afford (3-bromophenyl)(2,2-diethoxyethyl)sulfane (8.23 g, 100%) as a colorless oil. |
95% | With potassium carbonate In acetone for 2h; | 104.A Into a stirred solution of 3-bromothiophenol (50.09 g, 264.9 mmol) and K2CO3 (36.61 g, 264.9 mmol) in acetone (361 mL) is added bromoacetaldehyde diethyl acetal (39.85 mL, 264.9 mmol) in a dropwise manner. After stirring for 2 h, the resulting slurry is filtered through a sintered glass funnel and the filtrate is concentrated under reduced pressure. The resulting precipitate is diluted with CH2Cl2 (200 mL), dried over MgSO4, EPO filtered and concentrated under reduced pressure to give 3-bromobenzenethio- acetaldehyde diethyl acetal as a yellow oil used in the next step as is (76.83 g, 95%). |
94% | With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 2h; | 95B Example 95B - (3-bromophenylY2.2-diethoxyethvnsulfane (B-197) To a mixture of 3-bromobenzenethiol (39 g, 0.21 mol) and 2-bromo-l ,l - diethoxy ethane (45 g, 0.23 mol) in N N-dimethylformamide (400 mL) was added potassium carbonate (31 g, 0.23 mol) at room temperature. The mixture was stirred at room temperature for 2 hours. On completion, the reaction mixture was quenched with water and extracted with ethyl acetate (3 x 250 mL). The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give compound B-197 (50 g, 94% yield) as a yellow oil. |
87% | ||
84% | With potassium carbonate In acetone at 20℃; | 28.A EXAMPLE 28; [0181] This example illustrates a preparation of 2-(benzo[δ]thiophen-6-yl)-6- nitroisoindolin-1-one in an embodiment of the invention.; Step A: Synthesis of (3-bromophenyl)(2,2-diethoxyethyl)sulfane as an intermediate; [0182] A mixture of 3-bromothiophene (2.52 g, 13.3 mmol), 2-bromo-l,l-diethoxy ethane (3.92 g, 19.9 mmol), potassium carbonate (2.75 g, 19.9 mmol), and acetone (10 mL) was stirred at room temperature overnight. After this time, one more equivalent of 2-bromo- 1,1- diethoxyethane was added, and the mixture was stirred for another 2 h. The mixture was poured into water and extracted with ethyl acetate. The organic layer was separated, dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography (silica, 0-30% ethyl acetate/hexanes) to give (3-bromophenyl)(2,2-diethoxyethyl)sulfane (3.42 g, 84%) as a colorless liquid: 1H NMR (500 MHz, CDCl3) δ 7.63 (t, J= 1.8 Hz, IH), 7.29 (m, 2H), 7.12 (d, J= 7.9 Hz, IH), 4.65 (t, J= 5.5 Hz, IH), 3.71-3.65 (m, 2H), 3.58-3.51 (m, 2H), 3.13 (d, J= 5.5 Hz, 2H), 1.20 (t, J= 7.0 Hz, 6H). |
With sodium ethanolate; sodium iodide | ||
With potassium carbonate In DMF (N,N-dimethyl-formamide) at 20℃; for 24h; | 1 Preparation of Intermediates 1A and 1B. A mixture of 3-bromothiophenol (25 g, 132 mmol, 1 eq.), bromoacetaldehyde diethyl acetal (25.5 g, 129 mmol, 0.98 eq.) and K2CO3 (27 g, 198 mmol, 1.5 eq.) in 200 mL of DMF was stirred at room temperature for 24 hours. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate 2 times. The combined organic layers were washed with 1 N NaOH, water, brine, dried with anhydrous Na2SO4, filtered, and concentrated under reduced pressure to provide 30 g of residue as an oil. 15 g of the residue was dissolved in dichloroethane (100 mL) and the solution was added dropwise into a boiling solution 35 g of PPA in 800 mL of dichloroethane. The reaction was kept at reflux for another hour. The solution was decanted from the residue and dichloroethane was added to the residue, stirred and decanted. The solution and the extracts were combined and concentrated under reduced pressure. The residue was dissolved in ethyl acetate and the solution was washed with 10% of Na2CO3 (aq.), water, brine, dried with anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was subjected to silica gel chromatography, eluting with hexane. The fractions containing product were combined and concentrated under reduced pressure to provide 9 g of intermediates 1A and 1B as an oil. | |
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 16h; | 350 Preparation Example 350: 4-bromo-benzo[b]thiophene 3-bromobenzenethiol (0.5 g, 2.64 mmol) was dissolved in 8 mL of DMF. bromoacetaldehyde diethyl acetal(0.52 g, 2.64 mmol) and K2CO3 (0.548 g, 3.97 mmol) were added thereto, and the mixture was stirred at room temperaturefor 16 hours. After addition of water, the reaction solution was extracted with EtOAc. The organic layer was dried withanhydrous magnesiumsulfate and concentrated under reduced pressure to obtain 1-bromo-3-(2,2-diethoxy-ethylsulfanyl)benzene. The obtained compound was dissolved in 8 ml of MC. 0.7 g of PPA (polyphosphoric acid) was addedthereto, and the mixture was stirred for 4 hours under reflux. After addition of Na2CO3 aqueous solution, the reactionsolution was extracted with MC. The organic layer was dried with anhydrous magnesiumsulfate and purified by columnchromatography to obtain the mixture of 4-bromo-benzo[b]thiophene and 6-bromo-benzo[b]thiophene (1:1, 0.33 g, 58 %).1H-NMR (CDCl3) δ 8.01 (1H, s), 7.80 (1H, d), 7.66 (1H, d), 7.50 (4H, m), 7.41 (1H, d), 7.29 (1H, d), 7.19 (1H, t) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In acetone; | Step 1 Preparation of 3-(methylthio)phenylbromide To a solution of 3-bromothiophenol (10 g) in acetone (250 mL) was added potassium carbonate (14.6 g) and iodomethane (4.28 mL). The heterogenous mixture was refluxed for 4 hrs., cooled to room temperature, filtered, and concentrated under reduced pressure. Ether (200 mL) was added, and the mixture was filtered again and finally evaporated to dryness to yield the title compound. 1 H NMR (CDCl3) delta: 2.46 (s, 3H), 7.10-7.55 (m, 4H). | |
With potassium carbonate; In acetone; | Step l : Preparation of 3-(methylthio)phenylbromide To a solution of 3-bromothiophenol (l0 g) in acetone (250 mL) was added potassium carbonate (l4.6 g) and iodomethane (4.28 mL). The heterogenous mixture was refluxed for 4 hrs., cooled to room temperature, filtered, and concentrated under reduced pressure. Ether (200 mL) was added, and the mixture was filtered again and finally evaporated to dryness to yield the title compound.. 1H NMR (CDCl3) delta: 2.46 (s,3H), 7.l0-7.55 (m,4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79.1% | With sodium hydroxide In water at 20℃; for 2h; Reflux; | 6.6-1 6-(1) Intermediate 6-a was synthesized according to Scheme 23 below 3-bromothiophenol (30.0 g, 0.159 mol) was added to a 1 L round bottom flask, and sodium hydroxide (63.47 g, 1.587 mol) was dissolved in 500 mL of water.2-chloroacetic acid (16.5 g, 0.175 mol) was added dropwise to the reaction solution, such as 100 mL of water.After stirring at room temperature for 30 minutes, the mixture was stirred at reflux for 1 hour and 30 minutes.After the reaction was completed, the mixture was cooled to room temperature, acidified to pH 1 with 2 mol hydrochloric acid, and extracted with acetic acid.The organic layer was separated to remove moisture with magnesium sulfate and concentrated under reduced pressure to obtain Intermediate 6-a. (31.0 g, 79.1%) |
78% | With sodium hydroxide In water at 20℃; for 2h; Heating / reflux; | 139.A Example 139; N-[3-(1-Benzo[b]thiophen-6-yl-1-ethyl-propyl)-1H-indol-7-yl]-methanesulfonamide; A. Preparation of: (3-Bromo-phenylsulfanyl)-acetic acid To a solution OF NAOH (5.28 g, 0.132 mol) in H20 (40 mL) is added 3-bromothiophenol (2.50 g, 13.2 mmol). A solution of 2-chloroacetic acid (1.49 g, 15.8 mmol) in H20 (5 mL) is added dropwise to the vigorously stirred biphasic reaction mixture. After stirring for 30 min at room temperature, the reaction mixture is refluxed for 1.5 h then cooled to room temperature. The reaction is acidified to-pH 1 using 2 M HC1 and extracted with ET20 (3 X 200 mL). The combined organic layer is dried (MGS04), filtered and concentrated to afford the sub-title compound (2.53 g, 78%) as a white solid which is used without further purification. mp 79-82 C. 'H NMR (300 MHz, CDC13) 6 3.68 (s, 2H), 7.17 (t, J= 7.9 Hz, 1H), 7.28-7. 43 (M, 2H), 7. 55 (T, J= 1.8 Hz, 1H), ~8. 80-11. 00 (BR S, 1H). APCI MS (Negative Mode) M/Z 245 [C8H7BRO2S-H]-. |
With sodium hydroxide |
With hydroxide In water | ||
With sodium hydroxide at 120 - 130℃; for 5h; | Materials General procedure: Phenylsulfinylacetic acid and several para- and meta substituted phenylsulfinyl acetic acids were prepared from the corresponding phenylmercaptoacetic acids by controlled oxidation using equimolar quantity of H2O2 and recrystallised from suitable solvents. The recrystallised phenylsulfinylacetic acids were dried, melting points were determined and checked with the literature values. Thepurity was also ascertained by LC-MS for all the phenylsulfinylacetic acids. Then they were stored in the vacuum desiccator and used for the kinetic studies. Phenylmercaptoacetic acids required for the synthesis of PSAAs were synthesized by condensing chloroacetic acid (4.7 g in 20 ml of 20% sodium hydroxide) with appropriate thiophenol (0.05 mole) dissolved in 10 ml of 20% sodium hydroxide at 120-130°C for five hours. The phenylmercaptoacetic acids formed were recrystallised from water and their melting points were verified with the literature values.32 Potassium dichromate (Merck), sodium perchlorate (Merck), perchloric acid (Merck) and all other reagents used were of AnalaR grade. Solvents, acetonitrile and water were purified by established procedures. | |
Alkaline conditions; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium hydroxide In N,N-dimethyl-formamide | |
Stage #1: 3-Bromothiophenol With potassium hydroxide In water; N,N-dimethyl-formamide for 0.25h; Stage #2: ethyl iodide In water; N,N-dimethyl-formamide at 20 - 70℃; for 3h; | 3 To a solution of 3-bromothiophenol (3.0 g, 15.9 mmol) in DMF (40 mL) was added 10N KOH (1.75 mL, 17.4 mmol) followed 15 min later, by iodoethane (2.5 mL, 32 mmol). This mixture was stirred 1h at room temperature and 2h at 70 °C. The product was extracted twice using Et2O. The combined organic phases were washed with brine and dried over MgSO4. Purification by flash chromatography (100% hexanes) provided 3.2 g of the title compound as an orange oil. 1H NMR (acetone d6) δ 7.47 (m, 1H), 7.35-7.22 (m, 3H), 3.02 (q, 2H), 1.30 (t, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With 1,8-diazabicyclo[5.4.0]undec-7-ene In benzene for 2h; Heating; | |
64% | With potassium carbonate In N,N-dimethyl-formamide at 120℃; for 16h; | 7 To a stirred solution of 3-bromobenzenethiol (0.15 g, 0.79 mmol) in DMF (5 mL) were added potassium carbonate (0.329 g, 2.38 mmol) and ethyl 2-bromoacetate (0.132 g, 0.793 mmol). The resulting mixture was heated at 120 °C for 16 h. The reaction mixture was diluted with water (100 mL) and extracted into EtOAc (2x50 mL). The combined organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resultant residue was purified by silica gel column chromatography using CombiFlash (12 g REDISEP column) with 8% ethyl acetate in hexane as an eluent to yield ethyl 2-((3-bromophenyl)thio)acetate (0.14 g, 64%). XH NMR (400 MHz, CDC13) δ ppm: 1.25 (t, J= 12 Hz, 3 H), 4.21 (q, J= 12 Hz, 2 H), 7.17 (t, J= 7.6 Hz, 1 H), 7.25-7.36 (m, 2 H), 7.55 (d, J= 1.6 Hz, 1 H). |
With potassium carbonate In acetonitrile at 20℃; for 2h; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With potassium carbonate In acetone for 24h; Reflux; | |
85.5% | Stage #1: 3-Bromothiophenol With sodium methylate In methanol at 20℃; for 0.5h; Stage #2: benzyl bromide In methanol at 20℃; Further stages.; | |
83% | Stage #1: 3-Bromothiophenol With sodium hydride; potassium carbonate In N,N-dimethyl-formamide at 0℃; for 0.333333h; Inert atmosphere; Stage #2: benzyl bromide In N,N-dimethyl-formamide at 20℃; for 16h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With potassium hydroxide In water; dimethyl sulfoxide | 1 (3-Bromophenyl)-(2,2-dimethoxyethyl)sulfane Example 1 (3-Bromophenyl)-(2,2-dimethoxyethyl)sulfane To a solution of 2-bromo-1,1-dimethoxy-ethane (49.2 g, 0.29 mol) and 3-bromo-benzenethiol (50.0 g, 0.26 mol) in dimethyl sulfoxide (400 cm3) is added a solution of potassium hydroxide (18.0 g, 0.32 mol) in water (40 cm3). The resulting solution is stirred at 23° C. for 17 hours. The reaction mixture is extracted with 40-60 petroleum (5*100 cm3) and the combined organic layer is washed with brine (2*100 cm3), dried over anhydrous magnesium sulphate and filtered. The filtrate is concentrated in vacuo to obtain (3-Bromophenyl)-(2,2-dimethoxyethyl)sulfane (65.0 g, 89%) as a colourless oil. MS (m/e): 278 (M+, 100%). 1H NMR (300 MHz, CDCl3) 7.52-7.50 (1H, m, ArH), 7.33-7.27 (2H, m, ArH), 7.15 (1H, dd, ArH, J 7.2, 7.2), 4.53 (1H, t, CH, J 5.6), 3.38 (6H, s, CH3), 3.12 (2H, d, CH2, J 5.6). |
70% | With potassium carbonate In N,N-dimethyl-formamide at 30℃; | 32 [0164] To a stirred solution of compound 3-bromo-benzenethiol (15O g, 0.80 mol) and compound 2-bromo-l,l-dimethoxy-ethane (135 g) in DMF (1500 mL) was added K2CO3 (165 g, 1.20 mol). The mixture was stirred overnight at room temperature (30 0C). The mixture was filtered and the solvent of the filtrate was removed under reduced pressure. The residue was re- dissolved in EtOAc (2000 mL), washed with NaOH (IM, 500 mL), brine, dried over Na2SO4 and concentrated to give a crude product, which was purified by column chromatography (silica, elute; PE to PE:EtOAc=5: 1) to afford the title compound (135 g, 70 %) as a light yellow oil. |
70% | With potassium carbonate In N,N-dimethyl-formamide at 30℃; | 61 To a stirred solution of compound 3-bromo-benzenethiol (150 g, 0.80 mol) and compound 2-bromo-l,l-dimethoxy-ethane (135 g) in DMF (1500 mL) was added K2CO3 (165 g, 1.20 mol). The mixture was stirred overnight at room temperature (30 0C). The mixture was filtered and the solvent of the filtrate was removed under reduced pressure. The residue was re-dissolved in EtOAc (2000 mL), washed with NaOH (IM, 500 mL), brine, dried over Na2SO4 and concentrated to give a crude product, which was purified by column chromatography (silica, elute; PE to PE:EtOAc=5:l) to afford the title compound (135 g, 70 %) as a light yellow oil. |
68% | Stage #1: 3-Bromothiophenol With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 0.5h; Stage #2: 1-bromo-2,2-dimethoxyethane In N,N-dimethyl-formamide at 20℃; for 2h; | 20.1 Step 1: 1-Bromo-3-[(2,2-diethoxyethyl)sulfanyl]benzene To a stirred solution of 3-bromothiophenol (10.0 g, 52.88 mmol) in DMF (180 mL) was added NaH (3.0 g, 63.45 mmol) portionwise at 0°C. After the addition, the reaction mixture was stirred at room temperature for 30 mi Bromoacetaldehyde dimethylacetal (6.85 mL, 58.17 mmol) was added dropwise and the resulting mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with EtOAc (250 mL) and washed with cold water and brine solution. The organic layer was dried over anhydrous sodium sulfate, concentrated under reduced pressure to afford the crude material which was purified by column chromatography using silica gel (100-200 mesh) and 2% EtOAc-hexane as eluent to afford 1-bromo-3-(2,2-dimethoxy- ethylsulphanyl)-benzene (11.0 g, 36.038 mmol, 68%) as colorless liquid. GCMS: 277 (mlz). |
With sodium methylate In methanol Heating; | ||
With potassium carbonate In acetone | I.N.T.2.A EXAMPLE INT2 Part A: A suspension of 3-bromothiophenol (15.2 g, 81 mmol), bromoacetaldehyde dimethylacetal (9.5 mL, 81 mmol) and potassium carbonate (12.2 g, 88 mmol) in acetone (90 mL) was stirred at ambient temperature overnight. The solid was filtered and rinsed with ether. Evaporation of the filtrate afforded 23 g of 1-bromo-3-((2,2-dimethoxyethyl)thio)benzene which was carried forward without further purification. | |
With potassium carbonate In acetone at 20℃; | INT2.A EXAMPLE INT2 [0252] Part A: A suspension of 3-bromothiophenol (15.2 g, 81 mmol), bromoacetaldehyde dimethylacetal (9.5 mL, 81 mmol) and potassium carbonate (12.2 g, 88 mmol) in acetone (90 mL) was stirred at ambient temperature overnight. The solid was filtered and rinsed with ether. Evaporation of the filtrate afforded 23 g of 1-bromo-3-((2,2-dimethoxyethyl)thio)benzene which was carried forward without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With CoCl2 In acetonitrile at 20℃; | |
80% | With magnesium(II) perchlorate at 20℃; for 5h; | |
With silver trifluoromethanesulfonate at 60℃; for 0.5h; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In N,N-dimethyl-formamide at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With tin(IV) chloride In dichloromethane at 20℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
A mixture of 3-bromothiophenol (25 g, 132 mmol, 1 eq.), bromoacetaldehyde diethyl acetal (25.5 g, 129 mmol, 0.98 eq.) and K2CO3 (27 g, 198 mmol, 1.5 eq.) in 200 mL of DMF was stirred at room temperature for 24 hours. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate 2 times. The combined organic layers were washed with 1 N NaOH, water, brine, dried with anhydrous Na2SO4, filtered, and concentrated under reduced pressure to provide 30 g of residue as an oil. 15 g of the residue was dissolved in dichloroethane (100 mL) and the solution was added dropwise into a boiling solution 35 g of PPA in 800 mL of dichloroethane. The reaction was kept at reflux for another hour. The solution was decanted from the residue and dichloroethane (100 mL×2) was added to the residue, stirred and decanted. The solution and the extracts were combined and concentrated under reduced pressure. The residue was dissolved in ethyl acetate and the solution was washed with 10% of Na2CO3 (aq.), water, brine, dried with anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was subjected to silica gel chromatography, eluting with hexane. The fractions containing product were combined and concentrated under reduced pressure to provide 9 g of intermediates 1A and 1B in approximate ratio of 4=6 as an oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With potassium carbonate In DMF (N,N-dimethyl-formamide) at 160℃; for 4h; Heating / reflux; | 44.1 To a suspension of m-fluoro-p-nitrotoluene (4.1 g,. 26.4 mmol) and K2CO3 (11 g, 79.5 mmol) in dry DMF (75 mL) under a nitrogen atmosphere was added p-bromothiophenol (5 g, 26.4 mmol) in single portion. The suspension was heated to reflux at 160° C. for 4 h then allowed to cool to RT. The mixture was then filtered through silica gel. The filtrated was concentrated and purified by flash chromatography on silica gel (ethyl acetate/hexanes 10% to 50%) to yield 156a (6.8 g, 79%) an orange oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | Stage #1: 3-Bromothiophenol With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: Ethyl 4-bromobutyrate In d<SUB>7</SUB>-N,N-dimethylformamide at 30℃; for 16h; | 102.1 To a mixture of 3-bromobenzenethiol (10 g, 52.89 mmol, 5.46 mL) in DMF (40 mL) was added NaH (3.17 g, 79.33 mmol, 60% purity) at 0 °C. The mixture was stirred at 0 °C for 30 min, followed by addition of ethyl 4-bromobutanoate (12.38 g, 63.47 mmol, 9.10 mL) . The mixture was allowed to warm to 30 °C and stirred for 16 hrs. The reaction was quenched by addition of saturated NH4CI solution (10 mL) then poured into water (400 mL) . The mixture was extracted with EA (50 mL_*3). The combined organic layer was washed with water (30 mL*1) and brine (30 mL*1), then dried over Na2SO4, filtered and concentrated under vacuum to give Intermediate B (8.3 g, 52% yield) as a yellow oil which was used to next step directly without further purification. |
With caesium carbonate In DMF (N,N-dimethyl-formamide) at 20℃; for 1h; | 9.A A solution of 3-bromothiol (IV-1,500 mg, 2.64 mmol), ethyl 4- bromobutyrate (378 GL, 2.64 mmol), and cesium carbonate (2.58 g, 7.92 mmol) in dimethylformamide (5 ml) was stirred at room temperature under nitrogen for 1 hour. The reaction was then diluted with diethyl ether, washed with 1M hydrochloric acid (2X50 mL), brine (50 mL), dried over sodium sulfate and concentrated. GC-MS: 302/304 (M+). The crude product was used without any further purification. | |
With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.166667h; | Step 1: Ethyl 4-((3-bromophenyl)thio)butanoate Step 1: Ethyl 4-((3-bromophenyl)thio)butanoate To a solution of 3-bromothiophenol (50 g, 265 mmol) in dry DMF (500 mL) at 0 °C was added NaH (12.7 g, 318 mmol, 60% in mineral oil). The mixture was stirred for 10 min, followed by the addition of ethyl 4-bromobutanoate (45.5 mL, 318 mmol). The cooling bath was removed and the mixture was stirred overnight. This was then diluted with water (1.5 L) and extracted with ethyl ether (3 x 300 mL). The extracts were combined and washed with water (2 x 100 mL), brine (100 mL) and dried over anhydrous Na2S04. The volatiles were removed by vacuum to furnish ethyl 4-((3-bromophenyl)thio)butanoate as a light brown oil, which was used directly in the next step. 1H NMR (CDC13) δ: 7.46 (t, J=1.9 Hz, 1H), 7.29-7.32 (m, 1H), 7.23-7.27 (m, 1H), 7.15 (t, J=1.0 Hz, 1H), 4.15 (q, J=7.3 Hz, 2H), 2.98 (t, J=7.3 Hz, 2H), 2.47 (t, J=7.3 Hz, 2H), 1.97 (quin, J=7.2 Hz, 2H), 1.27 (t, J=1.0 Hz, 3H) |
Stage #1: 3-Bromothiophenol With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.166667h; Inert atmosphere; Stage #2: Ethyl 4-bromobutyrate In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 16h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.17% | With potassium carbonate In acetone for 5h; Heating / reflux; | C-2 3-Bromobenzenethiol (1 g, 5.3 MMOL) was added to acetone (25 mL). Next was added potassium carbonate (1.46 g, 10.58 MMOL) and 2-iodopropane (1.17 g, 6.88 MMOL). This was REFLUXED for 5 h. Reaction was then cooled to rt and filtered through a pad of Celite. The organic was then concentrated in vacuo and taken up in ether at which time a white precipitate crashed out. The organic was then RE-FILTERED through the same celite plug and concentrated in vacuo to provide 1.14 G (93.17%) of 1-bromo-3- ISOPROPYLSULFANYL-BENZENE as an oil. 1 H-NMR (methylene chloride-d2) 8 7.54 (s, 1 H), 7.37-7. 31 (m, 2H), 7.18 (T, J=7. 9 HZ, 1 H), 3.50-3. 36 (m, 1H), 1.31 (d, J= 6. 1 HZ, 6H); LC- MS RT : 4.15, [M+H] + : 233.2. |
93.17% | With potassium carbonate In acetone for 5h; Heating / reflux; | 9; H-2 Example 9; Method H-2; Preparation of Alkvl aryl thioethers; Preparation of 1-Bromo-3-isopronvlsulfanyl-benzene; 3-Bromobenzenethiol (1g, 5.3 mmol) was added to acetone (25 mL). Next was added potassium carbonate (1.46 g, 10.58 mmol) and 2-iodopropane (1.17 g, 6. 88 mmol). This was refluxed for 5 h. Reaction was then cooled to rt and filtered through a pad of Celite. The organic was then concentrated in vacuo and taken up in ether at which time a white precipitate crashed out. The organic was then re-fiitered through the same celite plug and concentrated in vacuo to provide 1.14 g (93. 17%) of 1-bromo-3- isopropylsulfanyl-benzene as an oil. 1H-NMR (methylene chloride-d2) 5 7.54 (s, 1H), 7.37-7. 31 (m, 2H), 7.18 (t, J=7.9 Hz, 1H), 3.50-3. 36 (m, 1H), 1.31 (d, J= 6. 1Hz, 6H); LC- MS RT : 4.15, [M+H] + : 233.2. |
93.17% | With potassium carbonate In acetone for 5h; Heating / reflux; | 9 Preparation of l-Bromo-3-isopropvlsulfanvl-benzene. 3-Bromobenzenethiol (Ig, 5.3 mmol) was added to acetone (25 mL). Next was added potassium carbonate (1.46 g, 10.58 mmol) and 2-iodopropane (1.17 g, 6.88 mmol). This was refluxed for 5 h. Reaction was then cooled to rt and filtered through a pad of Celite. The organic was then concentrated in vacuo and taken up in ether at which time a white precipitate crashed out. The organic was then re-filtered through the same celite plug and concentrated in vacuo to provide 1.14 g (93.17%) of l-bromo-3-isopropylsulfanyl-benzene as an oil. IH-NMR (methylene chloride -d2) 7.54 (s, IH), 7.37-7.31 (m, 2H), 7.18 (t, J=7.9 Hz, IH), 3.50-3.36 (m, IH), 1.31 (d, J= 6.1Hz, 6H); LC-MS RT: 4.15, [M+H]+: 233.2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With triethylamine In tetrahydrofuran at 20℃; for 12h; | 20.a Example 20; 5-Bromo-4-(3'-formyl-biphenyl-3-sulfonyl)-thiophene-2-carboxamidine trifluoroacetate; a); 4-(3-Bromo-phenylsulfanyl)-5-nitro-thiophene-2-carboxylic acid methyl ester 4-Bromo-5-nitro-thiophene-2-carboxylic acid methyl ester ( (EXAMPLE 114, step c) 1 g, 3.75 mmol) and Et3N (523 IL, 3.75 mmol) were dissolved with THF (10 mL) into a round bottom flask with stir bar. To this 3-bromothiophenol (467 GEL, 4.51 mmol) was added with stirring. The reaction became turbid therefore additional THF (12 mL) was added. The reaction was stirred at rt for 12 hours. The reaction mixture was concentrated in vacuo and then dissolved into EtOAc. The organic layer was washed several times with saturated NAHC03 and brine. The combined organic layers were dried over sodium sulfate. Removal of the solvents IF2 vacuo yielded the title compound (1.40 g, quantitative yield), which was used without further purification. 1H- NMR (CDC13) : δ 7.79 (t, 1H, J = 1.8 Hz), 7.67-7. 70 (m, 1H), 7.54-7. 85 (m, 1H), 7.37-7. 41 (t, 1H, J = 7.9 Hz), 6. 87 (s, 1H), 3.88 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 3-Bromothiophenol; acrylonitrile With N-benzyl-trimethylammonium hydroxide Heating / reflux; Stage #2: With acetic acid Heating / reflux; Stage #3: With sulfuric acid | Thus, in accordance with Reaction Scheme 8,5-bromothiophenol (available from Aldrich) is reacted with the reagent Triton B (benzyltrimethylammonium hydroxide, available from Alrich), thereafter refluxed with acidic acid, and thereafter treated with concentrated sulfuric acid to yield 7-bromo-thiochroman-4-one (Compound 19). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 16h; | 66 4, 4-Dimethylthiochromane- 7 -thiol [00843] 1 -Bromo-3-methylbut-2-ene (1 .94 mL, 16.8 mmol) was added to a mixture of 3- bromothiophenol (1 .91 mL, 18.5 mmol), K2CO3 (138) and DMF (56 mL). The reaction was stirred at rt for 16 h. EtOAc (120 mL) was added. The organic phase was washed with 1 :1 H20/brine (4 χ 100 mL), dried over MgS04 and filtered. The solvent was removed under reduced pressure to give (3- bromophenyl)(3-methylbut-2-en-1 -yl)sulfane as a colourless oil (4.29 g; quant). (3-bromophenyl)(3- methylbut-2-en-1 -yl)sulfane (2.40 g, 9.33 mmol) was dissolved in toluene (10.4 mL). p-TSA (2.66 g, 14.0 mmol) was added and the mixture was stirred at 165 °C (microwave) for 45 min. After cooling to rt, EtOAc (80 mL) was added. The organic phase was washed with sat. NaHC03 (3 χ 80 mL), dried over MgS04 and filtered. The solvent was removed under reduced pressure. The crude was purified by column chromatography (EtOAc/cyclohexane 0→5%) to afford a colourless oil containing mostly the desired 7-bromo-4,4-dimethylthiochroman and the regioisomer 5-bromo-4,4-dimethylthiochroman (2.42 g, 5.3:1 ; quant). |
In ice-water; N,N-dimethyl-formamide | 5.2.1 Step 1 Step 1 A solution of 3-bromothiophenol (5.0 g) in 60 mL of DMF was treated with 3.75 g of ground potassium carbonate and 3.2 mL of 3,3-dimethylallyl bromide. The reaction mixture was stirred at room temperature for two hours, poured onto 75 mL of ice-water, acidified to pH 2.0 with 10% HCl and extracted with three 75 mL portions of ether. The organic phase was dried over MgSO4, filtered and concentrated in vacuo to give a yellow oil. The product was purified by short path distillation (T=170° C. at 950 mTorr) to give 5.651 g of 1-bromo-3-(3-methyl-but-2-enylsulfanyl)-benzene as a colorless liquid. | |
With potassium carbonate In N,N-dimethyl-formamide | 34.h 2'-(4,4-Dimethylthiochroman-7-yl)-[1,1';4',1"]terphenyl-4"-carboxylic Acid (h) 1-Bromo-3-(3-methylbut-2-enylsulphanyl)benzene. 25.00 g (132.0 mmol) of 3-bromothiophenol, 200 ml of DMF and 18.23 g (138.0 mmol) of potassium carbonate are introduced into a three-necked flask. 18.0 ml (157.0 mmol) of 1-bromo-3-methyl-2-butene are added dropwise and the mixture is stirred at room temperature for five hours. The reaction medium is poured into water and extracted with ethyl acetate, and the organic phase is separated out after settling has taken place, washed with water, dried over magnesium sulphate and evaporated. 33.00 g (97%) of the expected compound are collected in the form of a yellow oil. 1H NMR (CDCl3) δ 1.62 (s, 3H), 1.73 (s, 3H), 3.54, (d, 2H, J=7.7 Hz), 5.28 (t, 1H, J=7.7 Hz), 7.09 to 7.15 (m, 1H), 7.22 to 7.31 (m, 2H), 7.45 (s, 1H). |
In <i>N</i>-methyl-acetamide; water | 3 EXAMPLE 3 The phosphonium salt used as the starting material can be prepared as follows: 36 g of 3-bromothiophenol were dissolved in 400 ml of dimethylformamide. After the addition of 27 g of finely powdered potassium carbonate and 29 g of 3,3-dimethylallyl bromide, the mixture was stirred at room temperature for 1 hour, diluted with 500 ml of water, acidified with 3N hydrochloric acid while cooling and extracted with ether. The yellow-brown oil obtained after evaporation was distilled in a high vacuum. There were obtained 48 g of m-bromophenyl 3-methyl-2-butenyl sulfide as a colorless liquid, boiling point 85° C./13.3 Pa. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With CuI In N,N-dimethyl-formamide; N-Boc-4-iodoaniline | 8.1.2 Step 1. Step 2, Preparation of 3-(4-aminophenylthio)bromobenzene. A mixture of 3-bromothiophenol (3.00 g, 15.9 mmol), N-t-Boc-4-iodoaniline (5.00 g, 15.9 mmol), prepared as in step 1, CuI (756 mg, 4.00 mmol), and K2 CO3 (4.40 g, 31.7 mmol) in DMF was heated at reflux under N2 for 2 hours. The reaction mixture was poured into H2 O/ ethyl acetate and filtered through a pad of celite. The organic phase was washed twice with saturated aqueous NH4 Cl, once with H2 O, and twice with brine, dried over MgSO4, filtered, and concentrated in vacuo. Chromatography on silica gel (20% ethyl acetate/hexanes) provided 3-(4aminophenylthio)bromobenzene (1.56 g, 35%). 1 H NMR (300 MHz, CDCl3) δ7.32 (2H, dt, J=9, 2, 2 Hz), 7.18-7.24 (2H, m), 6.97-7.07 (2H, m), 6.69 (2H, dt, J=9, 2, 2 Hz), 3.85 (2H, br s). MS m/e 280/282 (M+H)+, 297/299 (M+NH4)+. |
35% | With CuI In N,N-dimethyl-formamide; N-Boc-4-iodoaniline | 5.2 Step 2. Step 2. Preparation of 3-(4-aminophenylthio)bromobenzene A mixture of 3-bromothiophenol (3.00 g, 15.9 mmol), N-t-Boc-4-iodoaniline (5.00 g, 15.9 mmol), prepared as in step 1, CuI (756 mg, 4.00 mmol), and K2 CO3 (4.40 g, 31.7 mmol) in DMF was heated at reflux under N2 for 2 hours. The reaction mixture was poured into H2 O/ethyl acetate and filtered through a pad of celite. The organic phase was washed twice with saturated aqueous NH4 Cl, once with H2 O, and twice with brine, dried over MgSO4, filtered, and concentrated in vacuo. Chromatography on silica gel (20% ethyl acetate/hexanes) provided 3-(4-aminophenylthio)bromobenzene (1.56 g, 35%). 1 H NMR (300 MHz, CDCl3) δ 7.32 (2H, dt, J=9, 2, 2 Hz), 7.18-7.24 (2H, m), 6.97-7.07 (2H, m), 6.69 (2H, dt, J=9, 2, 2 Hz), 3.85 (2H, br s). MS m/e 280/282 (M+H)+, 297/299 (M+NH4)+. |
35% | With CuI In N,N-dimethyl-formamide; N-Boc-4-iodoaniline | 8.2 Preparation of 4-{3-[4-((N',N'-dimethylaminocarbonyl)-N-methylamino)phenylthio]phenyl}-4-methoxytetrahydropyran Step 2. Preparation of 3-(4-aminophenylthio)bromobenzene. A mixture of 3-bromothiophenol (3.00 g, 15.9 mmol), N-t-Boc-4-iodoaniline (5.00 g, 15.9 mmol), prepared as in step 1, CuI (756 mg, 4.00 mmol), and K2 CO3 (4.40 g, 31.7 mmol) in DMF was heated at reflux under N2 for 2 hours. The reaction mixture was poured into H2 O/ethyl acetate and filtered through a pad of celite. The organic phase was washed twice with saturated aqueous NH4 Cl, once with H2 O, and twice with brine, dried over MgSO4, filtered, and concentrated in vacuo. Chromatography on silica gel (20% ethyl acetate/hexanes) provided 3-(4-aminophenylthio)bromobenzene (1.56 g, 35%). 1 H NMR (300 MHz, CDCl3) δ7.32 (2H, dt, J=9, 2, 2 Hz), 7.18-7.24 (2H, m), 6.97-7.07 (2H, m), 6.69 (2H, dt, J=9, 2, 2 Hz), 3.85 (2H, br s). MS m/e 280/282 (M+H)+, 297/299 (M+NH4)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate In N,N-dimethyl-formamide at 20 - 70℃; for 3.5h; | h Example h ; 2-(3-Bromo-phenylsulfanyl)-propionamide; To a mixture of 5,0 g 3-bromobenzenethiol and 5,96 g potassium carbonate in 50 ml DMF were added 3,86 g 2-bromopropionamide at RT. The mixture was warmed up and stirred at 70 C for 3,5 hrs. After cooling, 200 ml water were added and the mixture extracted 3 times with dichloromethane. Drying and evaporation of the organic phases yielded 6,5 g of the title product which was used without further purification. | |
Stage #1: 3-Bromothiophenol With potassium carbonate In N,N-dimethyl-formamide Stage #2: 2-bromo-propionic acid amide In N,N-dimethyl-formamide at 20 - 70℃; for 3.5h; | o To a mixture of 5.0 g 3-bromobenzenethiol and 5.96 g potassium carbonate in 50 ml DMF were added 3.86 g 2-bromopropionamide at RT. The mixture was warmed up and stirred at 700C for 3.5 hrs. After cooling, 200 ml water were added and the mixture extracted 3 times with dichloromethane. Drying and evaporation of the organic phases yielded 6.5 g of the title product which was used without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With triethylamine In tetrahydrofuran; diethyl ether; ethyl acetate | 286.d d d 4-(3-Bromo-phenylsulfanyl)-5-nitro-thiophene-2-carbonitrile Triethylamine (104 mL, 0.75 mol) was slowly added to a solution of 4-bromo-5-nitro-thiophene-2-carbonitrile (165 g, 0.708 mol, Example 286: step c) and 3-bromo-benzenethiol (78 mL, 0.76 mmol) in THF (1.2 L) at rt for 2 days. The solvents were removed in vacuo and the resulting residue was diluted in EtOAc, washed with saturated Na2CO3 solution, and dried over magnesium sulfate. The solvents were removed in vacuo and the residue was stirred in diethyl ether:hexanes (1:5) and filtered to afford the title compound as a yellow solid (232.7 g, 96%). 1H-NMR (DMSO-d6): δ 7.88-7.92 (m, 1H), 7.65-7.81 (m, 2H), 7.48-7.54 (m, 1H), 7.22 (s, 1H). |
60% | With triethylamine In tetrahydrofuran at 16.9 - 22.3℃; for 1.75h; | 25.25e A 12-L, three neck, round bottom flask equipped with a mechanical stirrer and temperature probe was charged with 4-Bromo-5-nitro-thiophene-2-carbonitrile(Example 25: step d; 273 g, 1.174 mol), 3-bromothiophenol (127 mL, 1.232 mol) and THF (4L). A cold water bath was added. Triethylamine (172 mL, 1.232 mol) was charged to a 250 mL addition funnel and added dropwise to the mixture over 45 min, resulting in a temperature increase from 16.90C to 22.30C. After 1 hour, the reaction was complete and transferred in portions to a 5-L rotary evaporator bulb and concentrated to dryness under vacuum. The solids were transferred to a 10-L glass carboy, diluted with EtOAc (2L) and satd. NaHCO3 (2L) and stirred vigorously. The resulting solid precipitate was removed by filtration, washed with H2O (IL) and dried in a vacuum oven resulting in the title compound as a bright yellow powder (241.56 g, 60 %). 1H-NMR (DMSO): δ 8.0 (IH, s), 7.8 (IH, d), 7.6 (IH, d), 7.3 (IH, t), 7.1 (IH, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Preparation 39 e-Bromo-benzord'lisothiazole-S-carobxyllic acidThe title compound is prepared essentially as described in Procedure 3 of WO2005/092890 A2 using 3-brotauno-be?zenetrrioi. ES/MS m/e 255.0 (M-1 ). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 5h; | 3-Bromobenzenethiol (0.40 g) and potassium carbonate (0.44 g) were suspended in N,N-dimethylformamide (4.2 mL), 3-<strong>[628-09-1]chloropropyl acetate</strong> (0.34 mL) was added, and the resulting mixture was stirred at 60 C. for 5 hours. The reaction mixture was partitioned between diethyl ether (40 mL) and water (10 mL). The organic layer was washed successively with water (10 mL×2) and brine (10 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was dissolved in methanol (8.5 mL), 28% sodium methoxide-methanol solution (0.08 mL) was added, and the resulting mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure and the residue obtained was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=3/1) to give the title compound (0.49 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | Stage #1: 3-Bromothiophenol With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: 2-Bromoethyl methyl ether In N,N-dimethyl-formamide for 17h; | 1.17.A Step A: Preparation of Intermediate (3-Bromophenyl)(2-methoxyethyl)sulfane.To a suspension of sodium hydride (96.6 mg, 2.42 mmol) in DMF (4.2 mL) was added 3-bromobenzenethiol (0.22 mL, 2.132 mmol). After stirring at room temperature for 30 min, 1- bromo-2-methoxyethane (0.22 mL, 2.341 mmol) was added to the reaction mixture. After stirring for 17 h, the reaction mixture was quenched with H2O and extracted with EtOAc. The combined organic layers were washed with H2O, brine, dried over MgSO4 and concentrated. The residue was purified through a silica gel column with 15% EtOAc/ 85% hexanes to afford the title compound (425.1 mg, 81%) as a colorless oil. 1H NMR (400 MHz, Methanol-^) δ ppm 3.13 (t, J= 6.5 Hz, 2 H), 3.33 (s, 3 H), 3.57 (t, J = 6.5 Hz, 2 H), 7.20 (dd, J= 7.9, 7.9 Hz, 1 H), 7.30 - 7.35 (m, 2 H), 7.50 - 7.52 (m, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium carbonate; In N,N-dimethyl-formamide; at 150℃; for 2.5h; | [0186] A mixture of 3-bromobenzenethiol (630 muL, 5.33 mmol), l-bromo-2,2- dimethoxypropane (715 muL, 5.29 mmol), and K2CO3 (1.10 g, 7.96 mmol) in DMF (11 mL) was heated at 150 0C for 2.5 hours. The crude reaction mixture was cooled, filtered, and concentrated. The residue was purified using flash chromatography (0-30% ethyl acetate in hexanes) to afford the title compound as a clear oil (1.66 g, 108% with some trapped solvent). The material was used as is for the next reaction. <n="50"/>[0187] 1H NMR (500 MHz, DMSO-J6) delta 1.33 (s, 3H), 3.12 (s, 6H), 3.25 (s, 2H), 7.25 (dd, J = 8.4, 7.5 Hz, IH), 7.36 (dd, J = 7.9, 1.9 Hz, 2H), 7.54 (t, J= 1.8 Hz, IH) |
97% | With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; | To a mixture of 3-bromobenzenethiol (8.7 g, 46 mmol) and l-bromo-2,2- dimethoxypropane (8.4 g, 46 mmol) in N, N-dimethylformamide (50 mL) was added potassium carbonate (9.5 g, 69 mmol) at room temperature. The mixture was stirred at 80 C overnight. On completion, the reaction mixture was quenched with water and extracted with ethyl acetate (3 chi 100 mL). The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give crude compound B-118 (13 g, 97% yield) as colorless oil. |
With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; | To a mixture of 3-bromobenzenethiol (8.7 g, 46 mmol) and l -bromo-2,2- dimethoxypropane (8.4 g, 46 mmol) in NN-dimethylformamide (50 mL) was added potassium carbonate (9.5 g, 69 mmol) at room temperature. The mixture was stirred at 80 C overnight. On completion, the reaction mixture was quenched with water and extracted with ethyl acetate (3 x 100 mL). The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give crude compound B-287 (13 g, 97% yield) as a colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 1h; | 73 5-[(3-bromophenyl)thio]-4-(2-fluoropyridin-3-yl)thiophene-2-carbaldehyde Reference Example 73 5-[(3-bromophenyl)thio]-4-(2-fluoropyridin-3-yl)thiophene-2-carbaldehyde To a solution of 5-bromo-4-(2-fluoropyridin-3-yl)thiophene-2-carbaldehyde (300 mg) in N,N-dimethylformamide (5 mL) were added potassium carbonate (189 mg) and 3-bromobenzenethiol (218 mg) at room temperature, and the mixture was stirred at room temperature for 1 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=19:1→9:1) to give the title compound as a pale-yellow oil (394 mg, yield 95%). 1H-NMR (CDCl3) δ: 7.16-7.30 (3H, m), 7.41-7.46 (2H, m), 7.81-7.91 (2H, m), 8.24-8.27 (1H, m), 9.84 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | With N-ethyl-N,N-diisopropylamine In toluene at 105℃; for 14h; | 135 tert-butyl ({5-[(3-bromophenyl)thio]-4-(2-fluorophenyl)-1,3-thiazol-2-yl}methyl)methylcarbamate Reference Example 135 tert-butyl ({5-[(3-bromophenyl)thio]-4-(2-fluorophenyl)-1,3-thiazol-2-yl}methyl)methylcarbamate tert-Butyl [5-bromo-4-(2-fluorophenyl)-1,3-thiazol-2-yl]methyl}methylcarbamate (1.0 g), 3-bromothiophenol (0.32 mL), tris(dibenzylideneacetone)dipalladium(0) (119 mg), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthine (150 mg) and N-ethyldiisopropylamine (0.88 mL) were stirred in toluene (15 mL) at 105° C. for 14 hr. The reaction mixture was allowed to cool to room temperature, water was added, and the mixture was extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate solution, water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=5:1) to give the title compound as a yellow oil (645 mg, yield 49%). 1H-NMR (CDCl3) δ: 1.42 (9H, brs), 2.99 (3H, brs), 4.67-4.72 (2H, m), 7.04-7.48 (8H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With caesium carbonate In acetonitrile at 20℃; for 2.16667h; | 1.G To a solution of 3-bromothiophenol (5 g, 26.4 mmol) and cesium carbonate (17.2 g, 52.8 mmol) in MeCN (75 ml) was added 4-fluorobenzyl bromide (3.57 ml, 29.1 mmol) over 10 minutes, and the resulting solution stirred at room temperature for 2 hours. The reaction was then quenched with water, and extracted with ethyl acetate. The separated organic phase was dried over anhydrous magnesium sulfate, filtered, and evaporated in vacuo to afford (3-bromophenyl)(4-fluorobenzyl)sulfane as an orange oil (8.85 g, quantitative yield). 1H NMR (d6 DMSO) 7.51 (IH, t, J 1.8Hz, Ar), 7.43-7.31 (4H, m, Ar), 7.25 (IH, d, J 7.8Hz, Ar), 7.18-7.11 (2H, m, Ar) and 4.29 (2H, s, SCH2). |
100% | With caesium carbonate In acetonitrile at 20℃; | 1.G To a solution of 3-bromothiophenol (5 g, 26.4 mmol) and cesium carbonate (17.2 g, 52.8 mmol) in MeCN (75 ml) was added 4-fluorobenzyl bromide (3.57 ml, 29.1 mmol) over 10 minutes, and the resulting solution stirred at room temperature for 2 hours. The reaction was then quenched with water, and extracted with ethyl acetate. The separated organic phase was dried over anhydrous magnesium sulfate, filtered, and evaporated in vacuo to afford (3-bromophenyl)(4-fluorobenzyl)sulfane as an orange oil (8.85 g, quantitative yield).1H NMR (d6 DMSO) 7.51 (1H, t, J 1.8 Hz, Ar), 7.43-7.31 (4H, m, Ar), 7.25 (1H, d, J 7.8 Hz, Ar), 7.18-7.11 (2H, m, Ar) and 4.29 (2H, s, SCH2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With potassium carbonate In acetone at 20℃; for 1h; | 134.1 Example 134 Preparation of 4-(3-(2-aminoethylthio)phenethyl)heptan-4-ol Step 1: 3-bromobenzenethiol (133) (3 g, 15.9 mmol), 2-bromoethanol (2.4 g, 19.1 mmol), and K2CO3 (4.4 g, 32 mmol) were combined in acetone (20 mL) and stirred at room temperature for 1 h. The acetone was removed under reduced pressure and the residue extracted from water with ethyl acetate. The ethyl acetate solution was washed with brine, dried with MgSO4, filtered, and concentrated under reduced pressure, giving the alcohol 134 as a yellow oil without purification. Yield (3.6 g, 97%): 1H NMR (400 MHz, CDCl3) δ 7.49 (t, J=2.0 Hz, 1H), 7.31 (ddd, J=0.8, 1.6, 8.0 Hz, 1H), 7.27 (ddd, J=0.8, 1.6, 8.0 Hz, 1H), 7.13 (t, J=7.6 Hz, 1H), 3.75 (t, J=6.4 Hz, 2H), 3.10 (t, J=6.4 Hz, 2H), 2.18 (brs, 1H). |
90% | With caesium carbonate In N,N-dimethyl-formamide at 50℃; for 12h; Inert atmosphere; | 7.1 A solution of 3-bromobenzenethiol (5.00 g, 26.4 mmol) in anhydrous DMF (30 mL) was treated with Cs2CO3 (17.2 g, 52.8 mmol) and 2-bromoethanol (3.90 g, 31.7mol) and heated to about 50 0C under nitrogen for 12h. DMF was distilled out completely and the residue was dissolved in DCM and washed with water and brine. Organic layer was dried over Na2SO4, evaporated and purified by column chromatography (silica) to afford 5.5 g (90%) of the title compound as pale yellow solid. 1H NMR (400MHz, CDCI3) δ [ppm] 7.53 (1 H, s), 7.36(1 H, m), 7.34 (1 H, m), 7.16 (1 H, t), 3.78 (2H, t), 3.14 (2H, t). MS (ESI"): 217.1. HPLC (Condition F): Rt 3.87 min (HPLC purity 99.8%). |
90% | With caesium carbonate In N,N-dimethyl-formamide at 50℃; for 12h; | 42.1 Step 1) Formation of 2-[(3-bromophenyl)thio]ethanol A mixture of 3-bromothiophenol (5.0 g, 26.4 mmol), 2-bromoethanol (3.9 g, 31.7 mmol) and cesium carbonate (17.2 g, 52.8 mmol) in anhydrous DMF (30 ml.) was heated at 500C for 12 hours. The solvent was removed under reduced pressure. The residue was taken up with DCM and washed with water and brine. The organic layer was dried (Na2SC>;4) and the solvent was removed under reduced pressure. Purification by flash chromatography (silica, PE/EtOAc) gave the title compound as a pale yellow solid (5.5 g, 90%). 1H-NMR (CDCI3, 400 MHz): δ 7.53 (s, 1 H), 7.35 (m, 1 H), 7.33 (m, 1 H), 7.16 (t, 1 H), 3.78 (t, 2H), 3.13 (t, 2H). |
90% | With caesium carbonate In N,N-dimethyl-formamide at 50℃; for 12h; Inert atmosphere; | |
90% | With caesium carbonate In N,N-dimethyl-formamide at 50℃; for 12h; | 42.1 A mixture of 3-bromothiophenol (5.0 g, 26.4 mmol), 2-bromoethanol (3.9 g, 31.7 mmol) and cesium carbonate (17.2 g, 52.8 mmol) in anhydrous DMF (30 ml_) was heated at 500C for 12 hours. The solvent was removed under reduced pressure. The residue was taken up with DCM and washed with water and brine. The organic layer was dried (Na2SO4) and the solvent was removed under reduced pressure. Purification by flash chromatography (silica, PE/EtOAc) gave the title compound as a pale yellow solid (5.5 g, 90%). 1H- NMR (CDCI3, 400 MHz): δ 7.53 (s, 1 H), 7.35 (m, 1 H), 7.33 (m, 1 H), 7.16 (t, 1 H), 3.78 (t, 2H), 3.13 (t, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With caesium carbonate In N,N-dimethyl-formamide at 50℃; for 12h; Inert atmosphere; | 6.1 A solution of 3-bromobenzenethiol (5.00 g, 26.4 mmol) in anhydrous DMF (30 mL) was treated with Cs2CO3 (17.2 g, 52.9 mmol) followed by 3-bromopropan-1-ol (4.40 g, 31.6 mmol). The mixture was heated to 50 0C under nitrogen for 12h. DMF was distilled out completely, and the residue was dissolved in DCM and washed with water, brine and dried over Na2SO4. The solvent was evaporated to afford 6.4 g (98%) of the title compound as pale yellow liquid.1H NMR (400MHz, CDCI3) δ [ppm] 7.46 (1 H, s), 7.30-7.25 (2H, m), 7.16-7.12 (1 H, m), 3.78 (2H, t), 3.07-2.99 (2H, m) 1.93-1.87 (2H, m). MS (ESI"): 247.1. HPLC (Condition E): Rt 3.36 min. |
98% | With caesium carbonate In N,N-dimethyl-formamide at 50℃; for 12h; | 36.1 Step 1 ) Formation of 3-[(3-bromophenyl)thio]propan-1-ol A mixture of 3-bromothiophenol (5.0 g, 26.4 mmol), 3-bromo-propan-1-ol (4.4 g, 31.6 mmol) and cesium carbonate (17.2 g, 52.8 mmol) in anhydrous DMF (30 ml.) was heated at 500C for 12 hours. The solvent was removed under reduced pressure. The residue was taken up with DCM and washed with water and brine. The organic layer was dried (Na2SO4) and the solvent was removed under reduced pressure to give the title compound as a pale yellow oil (6.4 g, 98%). 1H-NMR (CDCI3, 400 MHz): δ 7.46 (s, 1 H), 7.27 (m, 2H), 7.14 (m, 1 H), 3.77 (t, 2H), 3.03 (m, 2H), 1.90 (m, 2H). |
98% | With caesium carbonate In N,N-dimethyl-formamide at 50℃; for 12h; Inert atmosphere; |
98% | With caesium carbonate In N,N-dimethyl-formamide at 50℃; for 12h; | 36.1 A mixture of 3-bromothiophenol (5.0 g, 26.4 mmol), 3-bromo-propan-1-ol (4.4 g, 31.6 mmol) and cesium carbonate (17.2 g, 52.8 mmol) in anhydrous DMF (30 ml_) was heated at 500C for 12 hours. The solvent was removed under reduced pressure. The residue was taken up with DCM and washed with water and brine. The organic layer was dried (Na2SO4) and the solvent was removed under reduced pressure to give the title compound as a pale yellow oil (6.4 g, 98%). 1H-NMR (CDCI3, 400 MHz): δ 7.46 (s, 1 H), 7.27 (m, 2H), 7.14 (m, 1 H), 3.77 (t, 2H), 3.03 (m, 2H), 1.90 (m, 2H). |
With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 0.5h; | 24.3 3-Bromo-l-propanol (13.9 g, 0.1 mol) in DMF (10 mL) was added dropwise to a stirred mixture of 3-bromothiophenol (18.9 g, 0.1 mol) and Cs2CO3 (65.2 g, 0.2 mol) in DMF (50 mL) at room temperature. After 30 minutes the reaction was diluted with EtOAc and water. The layers were separated and the organic layer was washed with water and brine. The organic layer was dried with Na2SO4 and concentrated. The residue was dissolved in acetic acid (100 mL) and hydrogen peroxide (~30 % in water, 150 mL) was added slowly. The reaction mixture was heated to ~70 0C for 2 hours, treated with iced water, and extracted with EtOAc. The extracts were dried with Na2SO4 and concentrated. Chromatography on silica gel eluting with EtOAc:Hex gradient of 0:100 to 100:0 afforded the title compound as a white foam-solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.4% | With potassium carbonate In acetone at 20℃; for 18h; | 56.1 Step 1: 3-Bromobenzenethiol (1) (5 g, 26.45 mmol) was added to a mixture of n-butylbromide (3.62 g, 26.71 mmol) and K2CO3 (10.95 g, 79.35 mmol) in acetone and the reaction mixture was stirred at room temperature for 18 h. The reaction mixture was then filtered and the filter cake was washed with acetone. Concentration of the filtrate under reduced pressure gave thioether 70 as a light yellow oil. Yield (6.01 g, 93.4%); 1H NMR (400 MHz, CDCl3) δ 7.43-7.42 (t, J=2 Hz, 1H), 7.29-7.28 (t, J=1.2 Hz, 1H), 7.23-7.21 (m, 1H), 7.14-7.11 (t, J=7.6 Hz, 1H), 2.94-2.90 (t, J=7.2 Hz, 2H), 1.67-1.57 (m, 2H), 1.48-1.41 (m, 2H), 0.95-0.91 (t, J=7.6 Hz, 3H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With potassium carbonate In acetone at 20℃; for 18h; | 1.1 Step 1: 3-Bromobenzenethiol (1) (1.0 mL, 8.46 mmol) was added to a mixture of bromomethylcyclohexane (2) (1.53 g, 8.61 mmol), K2CO3 (2.47 g, 17.90 mmol) in acetone and the reaction mixture was stirred at room temperature for 18 h. The reaction mixture was then filtered and the filter cake was washed with acetone Concentration of the filtrate under reduced pressure gave thioether 3 as a light yellow oil. Yield (2.37 g, 99%); 1H NMR (400 MHz, CDCl3) δ 7.41 (t, J=1.8 Hz, 1H), 7.23-7.27 (m, 1H), 7.17-7.22 (m, 1H), 7.11 (t, J=7.8 Hz, 1H), 2.80 (d, J=6.8 Hz, 2H), 1.84-1.86 (m, 2H), 1.68-1.76 (m, 2H), 1.62-1.68 (m, 1H), 1.48-1.60 (m, 1H), 1.09-1.30 (m, 3H), 0.96-1.06 (m, 2H). |
86% | Stage #1: 3-Bromothiophenol With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: Cyclohexylmethyl bromide In N,N-dimethyl-formamide at 25℃; for 16h; | 179a 179a) (3-Bromophenyl)(cyclohexylmethyl)sulfane 179a) (3-Bromophenyl)(cyclohexylmethyl)sulfane To a solution of 3-bromobenzenethiol (4.158 g, 21 .99 mmol) in DMF (30 ml_) was added K2C03 (9.12 g, 66.0 mmol). The reaction mixture was stirred for 30 mins at room temperature. Then (bromomethyl)cyclohexane (4.28 g, 24.19 mmol) was added. The reaction mixture was stirred at 25°C for 16 h. Then it was poured into water (50ml_) and extracted with ethyl acetate(3x). The combined organic phase was concentrated to obtain the title compound (3-bromophenyl)(cyclohexylmethyl)sulfane (6g, 18.93 mmol, 86 % yield) which was used in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In acetone; at 90 - 130℃;Microwave irradiation; | <strong>[39774-26-0]2-Bromo-6-phenyl-pyridine</strong> (13) (100 mg, 0.43 mmol), K2CO3 (117 mg, 0.85 mmol) in acetone (2 mL) was added 3-bromothiophenol and the reaction mixture was heated in a CEM Discover microwave for 1×30 minutes at 90 C., then 4×2 hours at 130 C., followed by 1×8 hours at 130 C. The crude product was partially purified by column chromatography eluting with 10% EtOAc in heptane to give the title compound. Yield: 100 mg, 68%; LC-MS 4.1.97 min; HPLC Purity: 55%; MS (ES+) m/z 342, 344 (M+H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With potassium carbonate In N,N-dimethyl-formamide at 50℃; for 12h; Inert atmosphere; | 5.1 A solution of 3-bromobenzenethiol (5.00 g, 26.4 mmol) in anhydrous DMF (30 mL) was treated with K2CO3 (7.30 g, 52.8 mmol) followed by 1-bromopropane (3.90 g, 31.7 mmol) and the mixture was heated to about 50 0C under nitrogen for 12h. The solvent was distilled out completely, and the residue was dissolved in DCM and washed with water and brine. The organic layer was dried over sodium sulphate and evaporated to afford 5.50 g (90%) of the title compound as pale yellow liquid. 1H NMR (400MHz, CDCI3) δ [ppm] 7.44 (1 H, s), 7.29-7.27 (1 H, m), 7.24-7.21 (1 H, m), 7.15-7.1 1 (1 H, m), 2.90 (2H, t) 1.64-1.73 (2H, m), 1.04 (3H, t). |
90% | With potassium carbonate In N,N-dimethyl-formamide at 50℃; for 12h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With copper(l) iodide; potassium carbonate; ethylene glycol In isopropyl alcohol at 80℃; for 30h; Inert atmosphere; | 4.3. General procedure for the synthesis of 3-[(substituted)phenylthio]quinoline, 6a-p General procedure: The method of Kwong was used [7]. A mixture of Cu (I) iodide (20 mg, 0.10 mmol), K2CO3 (540 mg, 3.92 mmol), 3-iodoquinoline (500 mg, 1.96 mmol), substituted benzenethiol (0.21 mL, 1.96 mmol), ethylene glycol (0.22 mL, 3.92 mmol) and 2-propanol (2 mL) was heated at 80 °C and allowed to reflux under N2 for 30 h. After cooling to rt, the mixture was diluted with distilled H2O (20 mL) and then extracted with EtOAc (3 × 15 mL). The pooled organic layer was washed with brine (50 mL), dried over anhydrous Na2SO4 and concentrated by rotary evaporation at reduced pressure to provide a crude product. The crude product was purified by column chromatography on silica gel using hexane: EtOAc (9.8: 0.2) to afford 3-[(substituted)phenylthio]quinoline. A typical reaction yield was found to be 90-95%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | Stage #1: 3-Bromothiophenol With potassium carbonate In N,N-dimethyl-formamide for 0.0833333h; Inert atmosphere; Stage #2: 1-Iodododecane In N,N-dimethyl-formamide at 20℃; for 16h; | 8.1 EXAMPLE 8; Synthesis of 1-[3-(dodecylthio)phenyl]-1-hydroxy-1,2-dihydro-3H-pyrrolo[3,4-c]pyridin-3-one (9) Step 1: Synthesis of 1-bromo-3-(dodecylthio)benzene (9a) Potassium carbonate (1.6 g; 11.8 mmol) is added to a solution of 3-bromobenzene thiol (1.50 g; 7.9 mmol) in dimethylformamide (90 ml) and the system is left in an inert atmosphere for 5 minutes with stirring, and subsequently 1-iododecane (3.5 g; 11.8 mmol) is introduced. After 16 h of reaction at ambient temperature, 50 ml of water are added, the reaction medium is extracted with ethyl acetate (3×30 ml), and the organic phases are recovered, dried over sodium sulphate and concentrated in a vacuum. The product obtained 9a, in the form of a colourless oil (4.5 g), is purified by chromatography in a silica gel column (eluent: cyclohexane), yielding 1.9 g (70%).IR (cm-1): 2921 (C-H), 2851 (C-H), 1576 (CC), 1458 (C-S), 1068, 753, 676 (C-Br); NMR 1H (250 MHz, CDCl3) δ (ppm): 7.46 (dd, 1H, J=6.7 Hz and 1.6 Hz); 7.23-7.32 (m, 2H, H4); 7.16 (dd, 1H, J=12.0 Hz and 7.8 Hz); 2.97 (t, 2H, J=7.2 Hz); 1.65 (t, 2H, J=7.3 Hz); 1.29 (m, 18H); 0.91 (t, J=6.6 Hz, 3H). NMR 13C (63 MHz, CDCl3) δ (ppm): 139.8 (C); 130.7 (CH); 130.0 (CH); 128.5 (CH); 126.9 (C); 122.8 (C); 33.3 (CH2); 31.9 (CH2); 29.7-28.8 (8×CH2); 22.7 (CH2); 14.1 (CH3). MS (DCl/CH4) m/z: 357 (M+H+); 385 (M+C2H5+). HR-MS: for C18H30SBr: theoretical mass: 357.1236; calculated mass: 357.1252. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | To a cooled (0 C) solution of potassium tert butoxide (0.36 g, 2.9 mmol) in DMSO (12 mL) was added 3-bromothiophenol (0.50 g, 2.6 mmol) under a nitrogen atmosphere and the reaction mixture was stirred for 15 min. A solution of <strong>[4333-56-6]cyclopropylbromide</strong> (0.96 g, 7.8 mmol) in DMSO (1.0 mL) was added dropwise. The reaction mixture was allowed to warm to rt, and followed by heating to 80 C for 48 hrs. The reaction mixture was cooled to rt and diluted with cold water (10 mL) and EtOAc (10 mL). The layers were separated and the aqueous layer was extracted EtOAc (20 mL x 2). The combined organic extracts were washed with water, brine, dried over Na2S04 and concentrated in vacuo to give the title compound (0.40 g, 66% yield). MS (ESI) 230.1 [M+H]+.. | |
60% | To a cooled (0 C) solution of potassium tert butoxide (0.36 g, 2.9 mmol) in DMSO (12 mL) was added 3-bromothiophenol (0.50 g, 2.6 mmol) under a nitrogen atmosphere and the reaction mixture was stirred for 15 mm. A solution of <strong>[4333-56-6]cyclopropylbromide</strong> (0.96 g, 7.8 mmol) in DMSO (1.0 mL) was added dropwise. The reaction mixture was allowed to warm to rt, and followed by heating to 80 C for 48 hrs.The reaction mixture was cooled to rt and diluted with cold water (10 mL) and EtOAc (10 mL). The layers were separated and the aqueous layer was extracted EtOAc (20 mL x 2). The combined organic extracts were washed with water, brine, dried over Na2504 and concentrated in vacuo to give the title compound (0.40 g, 66% yield). MS (ESI) 230.1 [M+H].. | |
57.7% | With caesium carbonate; sodium iodide; In N,N-dimethyl-formamide; at 120℃; for 16h; | Step-3: <strong>[4333-56-6]Bromocyclopropane</strong> (13 g, 105.82 mmol, 2.0 eq.), CS2CO3(51 g, 158.73 mmol, 3.0 eq.) and Nal (793 mg, 5.29 mmol, 0.1 eq.) wereadded to a stirred solution of 3-bromobenzenethiol (10 g, 52.91 mmol, 1.0eq.) in DMF (100 mL) at RT. The reaction mixture was heated to 120C for16 h after which time it was allowed to cool to RT. The reaction mixture wasthen washed with chilled water and brine (100 mL each). The organic layer was dried over Na2SO4 and concentrated under reduced pressure to obtain crude product. This material was purified by flash chromatography (over silica gel 100-200 mesh) eluting with 100 % petroleum ether to obtain pure I -bromo-3-(cyclopropylsulfanyl)benzene (7.0 g; 57.7 %). |
23% | With potassium tert-butylate; In dimethyl sulfoxide; at 80℃; for 5h; | Reference Example 5-38 1-Bromo-3-(cyclopropylsulfanyl)benzene Potassium t-butoxide (4 g) and <strong>[4333-56-6]cyclopropyl bromide</strong> (7.6 mL) were added to a solution of 3-bromothiophenol (6 g) in dimethyl sulfoxide (30 mL), and the mixture was stirred at 80 C. for five hours. The reaction solution was poured into water, followed by extraction with ethyl acetate. The organic layer was sequentially washed with water and brine, dried over sodium sulfate and filtered, after which the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1?7:3) to give the title compound as a light yellow oil (1.6 g, 23%). 1H NMR (300 MHz, CDCl3) delta ppm 0.63-0.77 (m, 2H), 1.04-1.18 (m, 2H), 2.11-2.25 (m, 1H), 7.09-7.17 (m, 1H), 7.22-7.29 (m, 2H), 7.48-7.53 (m, 1H). MS(+): 229 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 12h; Inert atmosphere; | General protocole for preparing of alkoxy/thioalkoxy-halogenobenzene General procedure: To a solution of halogenophenol (or bromobenzene thiol) (5.8 mmol) in dimethylformamide (60 mL) was added potassium carbonate (8.7 mmol) and the mixture was stirred under argon for 5 min, then 1-halogenoalkane (8.67 mmol) was introduced. After 12 h at room temperature, water was added (40 mL) and the mixture was extracted with ethyl acetate (3 x 30 mL). The organic layers were combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by column chromatography (SiO2) (cyclohexane) to give the desired compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium carbonate In N,N-dimethyl-formamide at 20℃; | al.1; az.1 Step 1 : 1-bromo-3-(isopropylthio)benzene2-Bromopropane (5.46 mL, 58.2 mmol) was added dropwise into a mixture of 3- bromothiophenol (6.29 mL, 52.9 mmol) and K2COs (10.96 g, 79.3 mmol) in anhydrous DMF (100 mL), and then stirred at RT overnight. The reaction mixture was diluted with water (200 mL) and extracted with TBE (3x150 mL). The combined organic layers were washed with brine, dried (MgS04) and concentrated under reduced pressure to give the title compound as a colourless oil (12.44 g, quantitative), used without further purification, UPLC/MS (max plot) 100%; Rt 2.23 min; ( S+) no signal. |
72% | With potassium carbonate In acetonitrile for 2h; Reflux; | 2.2 6.2.2 1-Bromo-3-isopropylsulfanyl-benzene (2) 3-Bromobenzenethiol (10.0 g, 52.9 mmol), 2-bromopropane (5.0 ml, 159 mmol) and K2CO3 (21.9 g, 159 mmol) were dissolved in acetonitrile (300 ml). The solution was brought to reflux and stirred for 2 h. After cooling, CH2Cl2 (200 ml) was added and the salts were filtered off. The filtrate was evaporated in vacuo to afford 11.8 g of crude product. Purification with flash chromatography using EtOAc as eluent afforded pure 2 (8.9 g, 72%). 1H NMR (400 MHz, CDCl3) δ 1.29 (d, J = 6.6 Hz, 6H), 3.38 (spt, J = 6.7 Hz, 1H), 7.13 (t, J = 7.8 Hz, 1H), 7.23-7.38 (m, 2H), 7.52 (t, J = 1.8 Hz, 1H). |
With potassium carbonate In acetone for 18h; Inert atmosphere; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | Stage #1: 3-Bromothiophenol; 2-(tert-butyldimethylsilyloxy)ethyl bromide With potassium carbonate In acetone at 20℃; Stage #2: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.166667h; Stage #3: di-tert-butyl-diazodicarboxylate In tetrahydrofuran; hexane at -78 - 20℃; for 2.66667h; | 3.a di-tert-butyl 1-{3-[(2-[tert-butyl(dimethyl)silyl]oxy}ethyl)sulfanyl]phenyl}hydrazine-1,2-dicarboxylate (Intermediate 3a) A mixture of 3-bromothiophenol (1.00 g, 5.29 mmol), bromoethoxydimethylsilyl ether (1.36 mL, 6.35 mmol) and potassium carbonate (1.46 g, 10.58 mmol) in acetone (15 mL) was stirred at RT overnight. The mixture was filtered, evaporated, the residue dried under vacuum, and then dissolved in dry THF (15 mL). nBuLi (1.6M in hexanes, 4.5 mL, 7.28 mmol) was added dropwise at -78°C and stirred for 10 min. Di-tert- butyl azodicarboxylate (1.54 g, 6.68 mmol) was added in one portion at -78°C and stirred for 20 min. The mixture was then allowed to warm to T over 2 h. The mixture was partitioned between saturated ammonium chloride (15 mL) solution and ethyl acetate (3 x 15mL). The combined organic extracts were washed with brine (20 mL), dried (Na2SO4) and concentrated in vacuo. The residue was purified by FCC, using 0-20% ethyl acetate in pentane, affording the title compound as a pale yellow oil (1.68 g, 64%). NMR (400 MHz, CDC13): 0.04 (6H, s), 0.84 (9H, s), 1.48 (18H, m), 3.04 (2H, t), 3.79 (2H, t), 7.14-7.24 (2H, m), 7.42 (1H, s). |
64% | Stage #1: 3-Bromothiophenol; 2-(tert-butyldimethylsilyloxy)ethyl bromide With potassium carbonate In acetone at 20℃; Stage #2: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.166667h; Stage #3: di-tert-butyl-diazodicarboxylate In tetrahydrofuran; hexane at -78 - 20℃; for 2.33333h; | 35.a a. Di-tert-butyl l-{3-[(2-[tert- butyl(dimethyl)silyl]oxy}ethyl)sulfanyl]phenyl}hydrazine-l,2-dicarboxylate (Intermediate 35a) a. Di-tert-butyl l-{3-[(2-[tert- butyl(dimethyl)silyl]oxy}ethyl)sulfanyl]phenyl}hydrazine-l,2-dicarboxylate (Intermediate 35a) A mixture of 3-bromothiophenol (1.00 g, 5.29 mmol), bromoethoxydimethylsilyl ether (1.36 mL, 6.35 mmol) and K2CO3 (1.46 g, 10.6 mmol) in acetone (15 mL) was stirred at RT overnight. The mixture was filtered, evaporated, and the residue re-dissolved in dry THF (15 mL) and cooled to -78°C. nBuLi (1.6M in hexanes, 4.5 mL, 7.28 mmol) was added dropwise and the mixture stirred for 10 min. Di-tert-butyl azodicarboxylate (1.54 g, 6.68 mmol) was added in one portion at -78°C and the mixture stirred for 20 min. The mixture was then allowed to warm to RT over 2 h. The reaction was quenched with sat. aq. NH4C1 solution (15 mL), then extracted with EtOAc (3 x 15 mL). The combined organic extracts were washed with brine (20 mL), dried (Na2SO4) and concentrated in vacuo. The residue was purified by FCC, using 0-20% EtOAc in pentane, to give the title compound as a pale yellow oil (1.68 g, 64%). NMR (400 MHz, CDC13): 0.04 (6H, s), 0.84 (9H, s), 1.48 (18H, m), 3.04 (2H, t), 3.79 (2H, t), 7.14- 7.28 (3H, m), 7.42 (1H, s). |
64% | Stage #1: 3-Bromothiophenol; 2-(tert-butyldimethylsilyloxy)ethyl bromide With potassium carbonate In acetone at 20℃; Stage #2: With n-butyllithium In tetrahydrofuran; hexane; acetone at -78℃; for 0.166667h; Stage #3: di-tert-butyl-diazodicarboxylate In tetrahydrofuran; hexane; acetone at -78 - 20℃; for 2h; | 3.a a. Di-tert-butyl 1-{3-[(2-[tert-butyl(dimethyl)silyl]oxy}ethyl)sulfanyl]phenyl}hydrazine-1,2-dicarboxylate (Intermediate 3a) a. Di-tert-butyl 1-{3-[(2-[tert-butyl(dimethyl)silyl]oxy}ethyl)sulfanyl]phenyl}hydrazine-1,2-dicarboxylate (Intermediate 3a) A mixture of 3-bromothiophenol (1.00 g, 5.29 mmol), bromoethoxydimethylsilyl ether (1.36 mL, 6.35 mmol) and potassium carbonate (1.46 g, 10.58 mmol) in acetone (15 mL) was stirred at RT overnight. The mixture was filtered, evaporated, the residue dried under vacuum, and then dissolved in dry THF (15 mL). nBuLi (1.6M in hexanes, 4.5 mL, 7.28 mmol) was added dropwise at -78° C. and stirred for 10 min. Di-tert-butyl azodicarboxylate (1.54 g, 6.68 mmol) was added in one portion at -78° C. and stirred for min. The mixture was then allowed to warm to RT over 2 h. The mixture was partitioned between saturated ammonium chloride (15 mL) solution and ethyl acetate (3*15 mL). The combined organic extracts were washed with brine (20 mL), dried (Na2SO4) and concentrated in vacuo. The residue was purified by FCC, using 0-20% ethyl acetate in pentane, affording the title compound as a pale yellow oil (1.68 g, 64%). 1H NMR (400 MHz, CDCl3): 0.04 (6H, s), 0.84 (9H, s), 1.48 (18H, m), 3.04 (2H, t), 3.79 (2H, t), 7.14-7.24 (2H, m), 7.42 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With potassium carbonate; In acetone; at 70℃; | A solution of <strong>[19047-31-5]2-chloro-N-cyclopropylacetamide</strong> (1.33 g, 10 mmol), 3- bromobenzenethiol (1.6 g, 8.5 mmol) and K2CO3 (4.8 g, 35 mmol) in 30 mL of acetone was heated at 70 C overnight. The mixture was filtered and concentrated to give a residue, which was purified by column chromatography (PE/EA, 1/1) to give the title compound (2.4 g, 96%) as a white solid. 1H NMR delta (300 MHz, CDC13) 7.39 (1H, m), 7.31 (1H, m), 7.14 (2H, m), 6.71 (1H, s), 3.58 (2H, s), 2.64-2.77 (1H, m), 0.73-0.84 (2H, m), 0.41 (2H, m); m/e 286 (M+H)+. |
96% | With potassium carbonate; In acetone; at 70℃; | Example 107 2-(3-bromophenylthio)-N-cyclopropylacetamide A solution of <strong>[19047-31-5]2-chloro-N-cyclopropylacetamide</strong> (1.33 g, 10 mmol), 3- bromobenzenethiol (1.6 g, 8.5 mmol) and K2CO3 (4.8 g, 35 mmol) in 30 mL of acetone was heated at 70 C overnight. The mixture was filtered and concentrated to give a residue, which was purified by column chromatography (PE/EA, 1/1) to give the title compound (2.4 g, 96%) as a white solid. 1H NMR delta (300 MHz, CDC13) 7.39 (1H, m), 7.31 (1H, m), 7.14 (2H, m), 6.71 (1H, s), 3.58 (2H, s), 2.64-2.77 (1H, m), 0.73-0.84 (2H, m), 0.41 (2H, m); m/e 286 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With potassium carbonate In water; N,N-dimethyl-formamide at 130℃; for 1h; | 7a Preparation of (3-bromophenyl) (difluoromethyl)sulfane A solution of 3-bromothiophenol (0.50 g, 2.6 mmol), K2C03 (0.73 g, 5.3 mmol)and sodium chiorodifluoroacetate (0.81 g, 5.3 mmol) in DMF (4.5 mL) and water (0.50mL) was heated to 130 °C for 1 hr. The reaction mixture was cooled to rt and diluted with diethyl ether (25 mL). The organic solution was washed with a citric acid solution, brine, dried over Na2SO4 and concentrated in vacuo to give the crude product. The crude product was purified by silica gel column chromatography using EtOAc : Hx (2:8) as an eluent toafford the title compound (0.60 g, 95% yield). MS (ESI) 239.8 [M+H]. |
95% | With potassium carbonate In water; N,N-dimethyl-formamide at 130℃; for 1h; | Intermediate 6a Preparation of (3-bromophenyl)(difluoromethyl)sulfane A solution of 3-bromothiophenol (0.50 g, 2.6 mmol), potassium carbonate (0.73 g, 5.3 mmol) and sodium chlorodifluoroacetate (0.81 g, 5.3 mmol) in DMF (4.5 mL) and water (0.50 mL) was heated to 130 °C for 1 hr. The reaction mixture was cooled to rt and diluted with diethyl ether (25 mL). The organic solution was washed with a citric acid solution, brine, dried over Na2S04 and concentrated in vacuo to give the crude product. The crude product was purified by silica gel column chromatography using EtOAc : Hx (2:8) as an eluent to afford the title compound (0.60 g, 95% yield). MS (ESI) 239.8 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With silver trifluoromethanesulfonate In dichloromethane at 20℃; for 0.5h; | General Procedure for the Synthesis of 2-alkynylbenzaldehydeThioacetals 3(a-l) To a stirred solution of 2-alkynylbenzaldehyde 1 (0.5mmol, 1 equiv) and silver triflate (0.05 mmol, 13 mg, 0.01equiv) in dichloromethane (2.0 mL), was added thiol 2 (1.1mmol, 2.2 equiv). The mixture was stirred at ambient temperature for the appropriate time (see Table 2). After completionof the reaction as indicated by TLC, the solvent wasevaporated and the residue was purified by column chromatographyon silica gel to provide the product 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With potassium carbonate In acetone at 60℃; | 8 6.1.8. 2-((3-Bromophenyl)thio)-N-(5-(pyrazin-2-yl)pyridin-2-yl)acetamide (18) 6.1.8 2-((3-Bromophenyl)thio)-N-(5-(pyrazin-2-yl)pyridin-2-yl)acetamide (18) To a solution of 3-bromobenzenethiol (137 mg, 0.73 mmol) and 12 (150 mg, 0.6 mmol) in acetone (10 mL) was added K2CO3 (334 mg, 2.42 mmol). The mixture was stirred at 60 °C overnight. After cooling to room temperature, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (dichloromethane/methanol = 50:1) to give 18 (178 mg, 74%) as a yellow solid. 1H NMR (400 MHz, CDCl3): δ 9.12 (s, 1H), 9.02 (d, J = 1.2 Hz, 1H), 8.97-8.91 (m, 1H), 8.65 (dd, J = 2.4, 1.6 Hz, 1H), 8.55 (d, J = 2.4 Hz, 1H), 8.39-8.30 (m, 2H), 7.54 (t, J = 1.8 Hz, 1H), 7.38-7.33 (m, 1H), 7.34-7.29 (m, 1H), 7.18 (t, J = 7.8 Hz, 1H), 3.82 (s, 2H). |
74% | With potassium carbonate In acetone at 60℃; | 1.14.1 Synthesis of Intermediate B14-2 B14-1 (150 mg, 0.60 mmol) and Bl-2 were added (137 mg, 0.73 mmol) was dissolved in decane (10 mL), potassium carbonate (334 mg, 2.42 mmol) was added, heated to 60 ° C and reacted overnight. After cooling to room temperature, the mixture was concentrated under reduced pressure and subjected to column chromatography (dichloromethane: petroleum ether = 50: 1) to give a yellow solid (178 mg, 74%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With potassium carbonate In acetonitrile at 80℃; for 2h; | 129.1 Step 1 : 2-(3-Bromophenylthio)-4-(furan-2-yl)-6-(trifluoromethyl)pyrimidine [00448] Potassium carbonate (0.103 g, 0.75 mmol) was added to a solution of 2-chloro-4-(furan- 2-yl)-6-(trifluoromethyl)pyrimidine (0.124 g, 0.5 mmol) and 3-bromobenzenethiol (0.08 mL, 0.75 mmol) in CH3CN (5 mL). After stirring for 2 h at 80 °C, the organic phase was evaporated under reduced pressure and the crude material was partitioned between water and CH2CI2. The aqueous layer was extracted with CH2CI2 (3 x 15 mL). The organic layer was dried over Na2SO4 and evaporated to give 2-(3-bromophenylthio)-4-(furan-2-yl)-6-(trifluoromethyl)pyrimidine (0.190 g, 94%). The crude product was used for the next step without further purification. LRMS (ESI) calcd. for C15H8BrF3N20S [M+H]+: 400.94, 402.94. Found: 401.0, 403.0. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94.6% | With potassium hydroxide In methanol at 1 - 20℃; for 24h; | 3 Preparation of 1,4-bis((3-bromophenyl)thio)butane (Compound 3, 1st int.) (0390) KOH (56.2 g) was added into methanol (1200 mL) in 15 min. The clear solution was cooled on water bath to 0° C. A solution of 3-bromo thiophenol (150.2 g, 0.79 mol) in methanol (200 mL) was added in 50 min keeping the temperature at 1-3° C. A solution of 1,4-dibromobutane (86.5 g; 0.40 mol) in methanol (150 ml) was added in 40 min to give a yellow turbid mixture. After additional 4 hours stirring the reaction mixture became white turbid and it was stirred for additional 20 h at 25° C. The suspension was filtered and washed with water (3×100 mL) and methanol (2×100 mL) to give 239 g wet white solid that was dried to 163.6 g (94.6% yield, HPLC: 97.9%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With potassium carbonate In N,N-dimethyl-formamide at 20 - 60℃; | Intermediate 79A: (3-Bromophenyl)(2-chloroethyl)sulfane A mixture of 3-bromobenzenethiol (1.09 mL, 10.6 mmol), 1-bromo-2-chloroethane (1.76 mL, 21.2 mmol) and K2CO3 (1.46 g, 10.6 mmol) in DMF (10.6 mL) was heated at 60° C. for 5 h. The mixture was cooled to room temperature and stirred overnight. After 16 h, the mixture was partitioned between water and ether. The organic phase was washed with brine, dried and concentrated to provide (3-bromophenyl)(2-chloroethyl)sulfane as a colorless oil (2.63 g, 99% yield), used without further purification. 1H NMR (400 MHz, CDCl3) δ 7.53 (t, J=1.8 Hz, 1H), 7.38 (ddd, J=8.0, 1.8, 1.0 Hz, 1H), 7.31 (ddd, J=7.8, 1.8, 1.0 Hz, 1H), 7.22-7.15 (m, 1H), 3.65-3.60 (m, 2H), 3.27-3.22 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; at 110℃; for 12h;Inert atmosphere; | General procedure: A mixture of the 2-chloroquinoline or the 2-chloropyridine (1equiv), substituted thiophenol (1.2equiv), K2CO3 (1.5equiv), and DMF (0.5M) was heated to 110C under N2 for 12h. The resulting mixture was diluted with EtOAc and filtered. The filtrate was washed with H2O three times, and then the organic layer was purified through column chromatography. The resulting product (1equiv) was dissolved in DCM (0.1M), and then meta-chloroperoxybenzoic acid (2.1equiv, 70%) was added at 0C under N2 and the mixture was stirred at room temperature for additional 12h. The reaction mixture was washed with cold 2N NaOH solution three times, and then the organic layer was collected and evaporated to provide the product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; at 110℃; for 12h;Inert atmosphere; | General procedure: A mixture of the 2-chloroquinoline or the 2-chloropyridine (1equiv), substituted thiophenol (1.2equiv), K2CO3 (1.5equiv), and DMF (0.5M) was heated to 110C under N2 for 12h. The resulting mixture was diluted with EtOAc and filtered. The filtrate was washed with H2O three times, and then the organic layer was purified through column chromatography. The resulting product (1equiv) was dissolved in DCM (0.1M), and then meta-chloroperoxybenzoic acid (2.1equiv, 70%) was added at 0C under N2 and the mixture was stirred at room temperature for additional 12h. The reaction mixture was washed with cold 2N NaOH solution three times, and then the organic layer was collected and evaporated to provide the product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate In N,N-dimethyl-formamide at 110℃; for 12h; Inert atmosphere; | General procedure for synthesis of 2-phenylsulfonylquinoline (10a-k) and 2-phenylsulfonylpyridine (20) General procedure: A mixture of the 2-chloroquinoline or the 2-chloropyridine (1equiv), substituted thiophenol (1.2equiv), K2CO3 (1.5equiv), and DMF (0.5M) was heated to 110°C under N2 for 12h. The resulting mixture was diluted with EtOAc and filtered. The filtrate was washed with H2O three times, and then the organic layer was purified through column chromatography. The resulting product (1equiv) was dissolved in DCM (0.1M), and then meta-chloroperoxybenzoic acid (2.1equiv, 70%) was added at 0°C under N2 and the mixture was stirred at room temperature for additional 12h. The reaction mixture was washed with cold 2N NaOH solution three times, and then the organic layer was collected and evaporated to provide the product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; at 110℃; for 12h;Inert atmosphere; | General procedure: A mixture of the 2-chloroquinoline or the 2-chloropyridine (1equiv), substituted thiophenol (1.2equiv), K2CO3 (1.5equiv), and DMF (0.5M) was heated to 110C under N2 for 12h. The resulting mixture was diluted with EtOAc and filtered. The filtrate was washed with H2O three times, and then the organic layer was purified through column chromatography. The resulting product (1equiv) was dissolved in DCM (0.1M), and then meta-chloroperoxybenzoic acid (2.1equiv, 70%) was added at 0C under N2 and the mixture was stirred at room temperature for additional 12h. The reaction mixture was washed with cold 2N NaOH solution three times, and then the organic layer was collected and evaporated to provide the product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With trifluoroacetic acid In dichloromethane at 0 - 20℃; for 0.75h; | 1 Step 1: (3-bromophenyl)(2 ,4,6-trimethoxybenzyl)sulfane A solution of 3-bromobenzenethiol (0.87 g, 4.59 mmol) and TFA (6 ml) in dry DCM(30 ml) at 0 00 was treated with a solution of (2,4,6-trimethoxyphenyl)methanol (1 g, 5.05 mmol) in DCM (15 ml) and the reaction stirred for 15 minutes before being allowed to warm to room temperature and stirred for 30 minutes. The reaction was diluted with DCM andwashed with Na2003. The organics were separated, washed with brine, dried over Na2504,filtered and concentrated. The residue was purified by flash chromatography (Biotage SP1, SNAP silica column, 0-10 % EtOAc/cyclohexane) to give the title compound as a colorless oil (1.4 g, 83 % yield). MS (mlz) 370.8 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With iodine In dimethyl sulfoxide at 110℃; for 10h; regioselective reaction; | |
99% | With iodine In dimethyl sulfoxide at 110℃; for 8h; | 12 Examples 1 to 12 General procedure: The imidazo [1,5-a] quinoline compound (II) was added to a 10 mL thick-walled pressure-resistant reaction tube according to the raw material ratio and the reaction conditions in Tables 1 and 2,Aryl thiophenol compounds (III),Catalysts and organic solvents,Mixing evenly,After completion of the reaction according to the reaction conditions in Table 2, extraction,Column chromatography (developing solvent is a mixture of ethyl acetate and petroleum ether,The ratio of the two is 1: 4-8) to obtain the corresponding thiomethylated imidazo [1,5-a] quinoline compound (I) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
15% | With trifluorormethanesulfonic acid; In dichloromethane; at 20 - 110℃; for 0.583333h;Inert atmosphere; Microwave irradiation; | General procedure: 2-trifluoromethylacrylic acid 2d (1.3 mmol, 182 mg) was transferred into a microwave vial with and a magnetic stir bar. 0.5 mL of dry CH2Cl2 was added to dissolve (partially) the acid. The solution was degassed with argon and cooled in an ice bath before the addition of the thiol (1, 1mmol). To the cooled reaction mixture 1.5 mL of CF3SO3H was added dropwise under argon atmosphere and the vial was sealed. The reaction was allowed to stir at room temperature for 30 minutes and subsequently subjected to microwave heating at 110 C for 5 minutes. After the reaction was completed, the reaction mixture was poured onto crushed ice and was quenched with solid NaHCO3. The quenched reaction mixture was extracted three times with CH2Cl2 and the combined organic extract was washed with aqueous NaHCO3 and water. The organic layer was dried over Na2SO4 and concentrated in vacuo to yield the crude product. Colored impurities were removed by addiction of activated charcoal followed by filtration. Further purification by column chromatography (hexanes/ethyl acetate) yielded the pure 3-(trifluoromethyl)thio-chroman-4-one (5). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | General procedure: Under inert atmosphere (N2, Schlenk flask), to a suspension of sodiumhydride (8.3 g, 346 mmol, 3.6 equiv) in freshly distilled dioxane (125 mL), phenols (144 mmol, 1.5 equiv) were introduced slowly (exothermic reaction and evolves H2 gas). To this mixture, the chlorodifluoroacetic acid (8.1 mL, 96.0 mmol, 1.0 equiv) was slowly addedat 0 C. Then, the solution was immersed in a temperature controlled oilbath to achieve a gentle reflux. The reaction progress was monitored by19F NMR. After 20-24 h, the acid was completely consumed and the mixture was concentrated in a rotary evaporator. The residue was dissolved in water (400 mL), and acidified with conc. HCl to reach pH= 1. Subsequenlty, the mixture was basified with NaHCO3 to reachpH= 8, and washed with DCM to remove the unreacted phenol. The solution was then acidified to pH= 1 and extracted with DCM(4 × 200 mL). After drying the combined organic layer with MgSO4 and filtration, the solvent was removed by rotary evaporation to obtain the compounds listed in Table 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With cerium(III) chloride heptahydrate In ethanol; dichloromethane at 20℃; for 16h; | 3.2.2. General Procedure for the Synthesis of Compounds 2-17 General procedure: A solution of 1 (150 mg, 0.4909 mmol) and CeCl3.7H2O (5% mmol respect to 1) in a mix ofethanol: dichloromethane = 1:1 (10 mL), was added dropwise slowly a solution of benzenethiol derivate (0.5 equiv.) in ethanol: dichloromethane = 1:1 (30 mL). The reaction mixture was stirred at room temperature for 16 h. The progress of the reaction was followed by thin-layer chromatography (TLC). The mixture was concentrated and the crude of reaction was purified using 65 g of silicagel (70±230 mesh) and a mix of dichloromethane, light petroleum and ethyl acetate than eluent indeterminate proportions. The resulting solution was concentrated to dryness under reduced pressure. |
82% | With cerium(III) chloride heptahydrate In methanol; dichloromethane for 16h; | 12 Example 12 Obtaining 8-(3-bromothiophenyl)-6-ethyl-2,4-dimethylpyrimido[4,5-c]isoquinoline-1,3,7,10(2H,4H)-tetraone (12) . A solution of 7 6-ethyl-2,4-dimethylpyrimido[4,5-c]isoquinoline-1,3,7,10(2H,4H)-tetraone (1) (598,6 mg, 2,0 mmol) and 10 heptahydrated cerium (III) trichloride (0.5% mole of 1) in a mixture of 6 CH2Cl2:MetOH=1:1 (10 ml), is added a solution of 3-bromothyiophenol (189.07 mg, 1.0mmol) dissolved in CH2Cl2:13 MetOH=1:1 (30 ml) by dripping from a burette at a rate of approximately 1ml/30min for 16 hours. The reaction crude is purified with 50-90 g of 0,063-0,2 mm Silica gel using an appropriate proportion of petroleum ether, dichloromethane and ethyl acetate as the mobile phase. An orange-colored solid of 398.8 mg, 0.82 mmol is obtained, with an 82% yield. (0114) Melting point 138.3 - 139.3°C. HRMS (M+): m/z calculated C21H16BrN3O4S [M+] = 485.00449; found = 485.00453. IR (KBr) : 1559 cm-1 C=O (quinone) ; 1668 cm-1 C=O (uracile). 1H RMN (CDCl3, 400 MHz): δ 1.3 (t, 3J=7.3 Hz, 3H, 6-CH2CH3), 3.43-3.38 (c, 2J=Hz, 2H, 6-CH2CH3), 3.44 (s, 3H, 4-NCH3), 3.76 (s, 3H, 2-NCH3), 6.21 (s, 1H, 9-H), 7.47 (c, 2J=Hz, 2H, 4' and 5'), 7.52 (d, J=7.1 Hz, 1H, 6') 7.55 (s, 1H, 2'). 13C RMN (CDCl3, 100 MHz): δ 12.5 (6-CH2CH3), 29.4 (4-NCH3), 30.5 (2-NCH3), 32.1 (6-CH2CH3), 105.8 (10a), 120.7 (6a), 124.2 (1'), 128.5 (9), 129.7 (3'), 132.0 (5'), 134.3 (6'), 134.6 (4'), 138.5 (2'), 147.5 (10b) 151.4 (3), 153.1 (1), 156.1 (8) 158.7 (4a), 171.2 (6), 180.8 (7), 181.6 (10). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With caesium carbonate In N,N-dimethyl-formamide at 110℃; Inert atmosphere; | 2 Synthesis of Compound 2 3-Bromothiophenol (64 ul, 0.5 mmol), 1a (127 mg, 0.25 mmol), 60748-47-2 (2.3 mg, 0.0025 mmol), 657408-07-6 (2.1 mg, 0.005 mmol) and cesium carbonate (245mg, 0.75mmol) added to 50mlIn a three-necked flask, the solvent was DMF, vacuumed, and replaced with nitrogen three times, placed at 110 ° C and stirred overnight. deal withIn the reaction, the catalyst, the ligand and the inorganic salt of the reaction solution are first filtered off with diatomaceous earth to obtain a black filtrate, which is then distilled off under reduced pressure.Solvent N,N-dimethylformamide to give a tan solid, add dichloromethane and extract twice with water, organic phaseDry with anhydrous magnesium sulfate, filter, and spin dry.Residue column chromatography,Obtained a yellow-brown solid 2The yield was 86%. |
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos In N,N-dimethyl-formamide at 110℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos In N,N-dimethyl-formamide at 110℃; Inert atmosphere; | 13 Synthesis of Compound 14 3-Bromothiophenol (50 ul, 0.60 mmol), 13b (200 mg, 0.50 mmol), 60748-47-2 (2.3 mg,0.0025mmol), 657408-07-6 (2.1mg, 0.005mol) and cesium carbonate (325mg, 1mmol) added to 50ml of threeIn the bottle, the solvent was DMF, vacuumed, and replaced with nitrogen three times, placed at 110 ° C, and stirred overnight. Handling the reaction,First, the catalyst, the ligand and the inorganic salt of the reaction liquid are filtered off with diatomaceous earth to obtain a black filtrate, and then the solvent is distilled off under reduced pressure.N,N-dimethylformamide gave a tan solid, which was taken in dichloromethane and extracted twice with water.Residue column chromatography,Obtained a yellow-brown solid 14,The yield was 80%. |
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos In N,N-dimethyl-formamide at 110℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | Stage #1: 1-bromo-butane; 3-Bromothiophenol With sodium hydride In acetonitrile at 20℃; for 0.5h; Inert atmosphere; Stage #2: With 3-chloro-benzenecarboperoxoic acid In dichloromethane at -10℃; for 0.5h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 90% 2: 7% | With pyridine; copper diacetate In dichloromethane at 50℃; for 16h; Inert atmosphere; Sealed tube; | 3. General procedure for the synthesis of cyclopropyl aryl sulfides General procedure: A sealed tube equipped with a magnetic stirring bar was charged with thiophenol 8 (1.0equiv), copper(II) acetate (1.0 equiv) and pyridine (3.0 equiv). Tricyclopropylbismuth 1 (2.5equiv), prepared as described above, was dissolved in anhydrous DCM (0.1 M) under argonand was added into the sealed tube. Argon was bubbled in the reaction mixture for 45seconds, then the tube was sealed and heated at 50 °C for 16 hours. The reaction mixture wascooled to room temperature and silica gel was added. The mixture was concentrated underreduced pressure, and the crude product was purified by flash column chromatography usingthe indicated solvent system to afford the corresponding aryl cyclopropyl sulfide 9 anddiarylsulfide 16 as a side-product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With palladium on zirconium oxide In acetonitrile at 30℃; for 12h; Irradiation; Green chemistry; | Visible light induced the high-efficiency spirocyclization reaction of propynamide and thiophenols General procedure: First, add N-methyl-N, 3-diphenyl-2-propynylamide (0.3 mmol), thiophenol (0.6 nmol), CH3CN (3 mL) to a glass tube with photocatalyst Pd/ZrO2 (0.006 mmol, 2 mol%). Then, the reaction mixture was irradiated with a tungsten halogen lamp (300 W) for 12 hours while the fan was turned on to lower the temperature to 30 °C. The reaction was purified by silica gel chromatography (3:1 petroleum ether/EtOAc) to get the products: 3a-3q. All reactions were carried out in an open system and the tungsten halogen lamp (wavelength of 400-750 nm) used as a source of visible light. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67.1% | With caesium carbonate; In acetonitrile; at 20℃; for 2h; | To a stirred solution of <strong>[62595-74-8]3-bromopiperidine-2,6-dione</strong> (150 mg, 0.785 mol) in CH3CN (15 mL) was added 3-bromobenzenethiol (193.1 mg, 1.021 mol), Cs2CO3 (332.8 mg, 1.021 mol) at r.t.. The reaction mixture was stirred at r.t. for 2 h. The mixture was filtered and the filtrate was concentrated in vacuo. The residue was purified via column chromatography (DCM / EtOAc = 5% - 80%) to give 3-((3-bromophenyl)thio)piperidine-2,6-dione (158.1 mg, 67.1 %) as a colorless oil. 1H NMR (400 Mz, CDCl3) delta 7.76 (s, 1H), 7.70 (t, J = 1.7 Hz, 1H), 7.48 (dd, J = 8.0, 1.7 Hz, 2H), 7.23 (t, J = 8.0, 1H), 3.97 (t, J = 5.0 Hz, 1H), 2.89- 2.82 (m, 1H), 2.67- 2.61 (m, 1H), 2.39- 2.33 (m, 1H), 2.20- 2.15 (m, 1H); LC/MS (ESI, m/z): [M +1]+ = 300.0/301.9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With N-Bromosuccinimide; di-tert-butyl peroxide; Bathocuproine; nikel(II) formate In benzene at 120℃; for 24h; Inert atmosphere; | 14 Example 14 The preparation of (1-phenylethyl) (3-bromophenyl) sulfide 3an is as follows: Under nitrogen protection, 3-bromothiophenol 2n (0.5 mmol), nickel formate dihydrate (0.025 mmol), BC (0.025 mmol), NBS (0.025 mmol), TBP (0.5 mmol), ethylbenzene 1a ( 7.5 mmol) and benzene (0.5 mL) were added to the reaction tube. Stir at 120 ° C for 24 hours. After stopping the reaction, cool to room temperature, evaporate the solvent and separate by column chromatography. The volume ratio (mL / mL) of the eluent used is ethyl acetate: petroleum ether = 0: 100 ~ 1: 100 to obtain (1-phenylethyl Alkyl) (3-bromophenyl) sulfide 3an, yield 89%. |
76% | With di-tert-butyl peroxide; Bathocuproine; nickel(II) acetate tetrahydrate at 140℃; for 24h; Inert atmosphere; Schlenk technique; | 3. General procedure for the oxidative dehydrogenative coupling reaction General procedure: Under nitrogen atmosphere, Ni(OAc)2*4H2O (6.2 mg, 0.025 mmol, 5 mol %), BC (11.0 mg, 0.03 mmol, 6 mol %), B1 (62.0 mg, 0.5 mmol, 1 equiv), DTBP (92.0 μL, 0.5 mmol, 1 equiv) and A1 (1.8 mL, 15 mmol, 30 equiv) were added into the reaction tube, and the mixture was stirred at 140 °C for 24 hours. After cooling to room temperature, the solvent was removed under reduced pressure. Then, the reaction mixture was purified by flash column chromatography on silica gel and eluted with petroleum ether to give the desired product 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: copper(l) iodide; 1,10-Phenanthroline; potassium carbonate / dimethyl sulfoxide / 24 h / Inert atmosphere 2: dihydrogen peroxide; acetic acid / 2 h / 120 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With sodium dihydrosulfite; triethylamine In lithium hydroxide monohydrate; acetonitrile at -20 - 25℃; Inert atmosphere; | 4.2. General procedure General procedure: Acetonitrile (150 mL), thiophenol (25 g, 227 mmol, 1 equiv.) andtriethylamine (25.3 g, 250 mmol, 1.1 equiv.) were placed in the flasksuccessively under stirring. The reaction mixture was cooled to -20 Cand the argon atmosphere was pumped out. A rubber balloon chargedwith CF3I (49 g, 250 mmol, 1.1 equiv.) was joined to the flask by a plug.After absorption of CF3I by the reaction solution, the flask was filled withan argon atmosphere. Sodium dithionite (39.5 g, 227 mmol, 1 equiv.)solution in H2O (100 mL) was added dropwise. Some self-heating forabout 1 to 30 C of the reaction mixture could be observed. Afterreaching ambient temperature (25 C) the reaction was judged completeand the mixture was ready for aqueous work up. |
20% | With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.25h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 84.4% 2: 10.1% | With aluminum dihydrogen phosphate; nitric acid In acetonitrile at 85℃; for 24h; | 4.3. General procedure using Al(H2PO4)3 / HNO3 /ACN (dry) (System B) General procedure: 32 mmol of halogenated thiol was dissolved in anhydrous ACN.0.16 mmol of aluminium dihydrogen phosphate (freshly prepared) andconcentrated HNO3 (3 mL) were added to this solution, which wasstirred at room temperature (r.t.) and monitored by TLC for 24 h, whenit was observed that the consumption of the starting material wascomplete. The method was optimized by increasing the temperature to85 °C, leading to faster formation of the thiosulfonate products withhigh yields. The workup was performed by neutralizing the mixture bycareful addition of a sodium bicarbonate solution. The mixture wasextracted using ethyl acetate. The organic layer was washed with distilledwater and brine and dried over MgSO4, followed by filtrationunder reduced pressure. The products were purified by silica gel (GF DE500 μm, UNIPLAT) chromatography using hexane/EtOAc (9:1) as theeluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With copper(l) iodide; potassium carbonate In 1,2-dimethoxyethane; isopropyl alcohol at 80℃; for 18h; Inert atmosphere; | |
82% | With copper(l) iodide; potassium carbonate In ethylene glycol; isopropyl alcohol at 80℃; for 18h; Sealed tube; Inert atmosphere; | 7.1 Step 1: An oven-dried round-bottom flask was charged with CuI (604 mg, 3.17 mmol, 0.1 eq) and K2CO3 (8.77 g, 63.5 mmol, 2 eq). The flask was sealed and evacuated/backfilled with nitrogen (3*). Isopropanol (125 mL) was added, followed by ethylene glycol (3.54 mL, 63.5 mmol, 2 eq), 3-bromothiophenol (3.28 mL, 31.7 mmol), and 3-bromoiodobenzene (4.45 mL, 34.9 mmol, 1.1 eq). The reaction mixture was stirred at 80° C. for 18 h. It was then diluted with saturated NH4Cl (200 mL) and EtOAc (200 mL), vigorously stirred for 30 min, and filtered through Celite. The filtrate was separated, and the aqueous layer was extracted again with EtOAc. The combined organics were washed with brine, dried over anhydrous MgSO4, filtered, and evaporated. Flash chromatography (100% hexanes, linear gradient) afforded 8.93 g (82%) of bis(3-bromophenyl)sulfane as a colorless oil. 1H NMR (CDCl3, 400 MHz) δ 7.48 (t, J=1.8 Hz, 2H), 7.40 (ddd, J=7.8, 1.9, 1.2 Hz, 2H), 7.28-7.23 (m, 2H), 7.18 (t, J=7.8 Hz, 2H); 13C NMR (CDCl3, 101 MHz) δ 137.3 (C), 133.8 (CH), 130.79 (CH), 130.75 (CH), 129.8 (CH), 123.3 (C); HRMS (EI) calcd for C12H8Br2S [M]+. 341.8708, found 341.8732. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With triethyl phosphite In chloroform at 20℃; for 4h; | Compounds 3; General Procedure General procedure: A 10-mL round-bottomed flask was charged with isatin 1 (0.5 mmol),thiophenol 2 (0.6 mmol), and CHCl3 (2 mL). Then the reaction mixturewas stirred at r.t. for 5 minutes, and triethyl phosphite (1.5 equivrelative to 1, 0.75 mmol, 124.5 mg) was added. The formation of theproduct was monitored by TLC. After completion of the reaction, thevolatiles were removed in vacuo and the residue was purified by columnchromatography (silica gel, EtOAc PE = 1:6) to afford the desiredproducts 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With potassium carbonate In tetrahydrofuran at 20℃; | α-Fluoro-β-ketosulfides 3a-u; General Procedure General procedure: A reaction tube containing a magnetic stir bar was charged with α-bromo-α-fluoroketone 1 (0.2 mmol, 1.0 equiv), sulfhydryl compound 2 (0.22 mmol, 1.1 equiv) and K2CO3 (0.22 mmol, 1.1 equiv). After THF (2.0 mL) had been added, the reaction tube was capped with a rubber stopper and the contents were stirred for 1-2 h at room temperature. The reaction mixture was then quenched with saturated aqueous NH4Cl solution and extracted with ethyl acetate. The combined organic phases were dried over Na2SO4, filtered and concentrated under vacuum. The crude product was purified by flash column chromatography on silica gel (PE/EtOAc = 20:1 to 100:1) to give the α-fluoro-β-ketosulfide 3a-u. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With triethylamine tris(hydrogen fluoride) In acetonitrile at 40℃; for 6h; Inert atmosphere; Electrochemical reaction; | Method A: General procedure for the electrochemical vicinal fluorosulfenylation of alkenes(constant cell-potential electrolysis) General procedure: In an oven-dried undivided three-necked glassware (25 mL) equipped with a stirring bar, thiophenolsubstrate (0.3 mmol) were added. The glassware was equipped with carbon cloth (15 mm × 15 mm ×0.1 mm) as the anode and platinum plate (15 mm × 15 mm × 0.3 mm) as the cathode. Under theprotection of N2, olefin substrate (1.5 equiv.), Et3N3HF (0.5 mL), and CH3CN (10 mL) were injectedrespectively into the glassware via syringes. The reaction mixture was stirred and electrolyzed at aconstant cell potential of 1.8 V at 40 oC for 6 h. The reaction mixture was subsequently poured into asaturated sodium bicarbonate solution (ca. 15 mL). The aqueous layer was separated and extracted withdichloromethane (3×5 mL), and the combined organic layers were washed with brine and dried oversodium sulfate. Following concentration in vacuo, the crude residue was subjected to flash columnchromatography on silica gel to yield the desired product. |
Tags: 6320-01-0 synthesis path| 6320-01-0 SDS| 6320-01-0 COA| 6320-01-0 purity| 6320-01-0 application| 6320-01-0 NMR| 6320-01-0 COA| 6320-01-0 structure
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