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CAS No. : | 10297-73-1 | MDL No. : | MFCD00025072 |
Formula : | C9H10O3S | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | KAVZYDHKJNABPC-UHFFFAOYSA-N |
M.W : | 198.24 | Pubchem ID : | 82529 |
Synonyms : |
|
Num. heavy atoms : | 13 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.22 |
Num. rotatable bonds : | 2 |
Num. H-bond acceptors : | 3.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 49.73 |
TPSA : | 59.59 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.89 cm/s |
Log Po/w (iLOGP) : | 1.31 |
Log Po/w (XLOGP3) : | 0.87 |
Log Po/w (WLOGP) : | 2.37 |
Log Po/w (MLOGP) : | 1.2 |
Log Po/w (SILICOS-IT) : | 1.47 |
Consensus Log Po/w : | 1.44 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.83 |
Solubility : | 2.95 mg/ml ; 0.0149 mol/l |
Class : | Very soluble |
Log S (Ali) : | -1.71 |
Solubility : | 3.91 mg/ml ; 0.0197 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -3.05 |
Solubility : | 0.177 mg/ml ; 0.000891 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.49 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H332-H335 | Packing Group: | N/A |
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 |
---|---|---|
52% | Stage #1: for 10 h; Heating / reflux Stage #2: With sodium hydroxide In water at 84℃; for 12 h; |
The synthesis was carried out as described in Scheme 2. Step a. A mixture of 4-(methylsulfonyl)acetophenone (5.5 g, 27.8 mmol), morpholine (2.5 mL), and sulfur (0.89 g, 27.8 mmol) was refluxed for 10 h, and poured into ice. The precipitated solid was filtered, and washed with cold ethyl acetate. The solid was added to 10percent sodium hydroxide (55 mL), heated to 84° C. for 12 h, and the alkaline solution was acidified with 12 N HCl. The resulting solid was filtered, dried, and recrystallized from hexane-ethyl acetate (1:1) to give 4-methylsulfonylphenylacetic acid (white solid, 4.2 g, 52percent overall yield). Step b. 2-Bromoacetophenone (1.02 g, 5.12 mmol), dissolved in acetonitrile, was added to Et3N (1.74 mL), followed by 4-methylsulfonylphenylacetic acid (1 g, 4.67 mmol). After 1.5 h at room temperature, 1,8-diazabicyclo[5,4,0]undec-7-ene (1.67 mL) was added. The reaction mixture was stirred for another 1 h, and then treated with 1 N HCl (35 mL). The product was extracted with ethyl acetate, dried over sodium sulfate, and recrystallized from ethyl acetate-hexane (1:1) to give 46b (880 mg, 60percent overall yield). 1H NMR (CDCl3) δ 3.08 (s, 3H), 5.24 (s, 2H), 7.18-7.30 (m, 5H), 7.66 (dd, J=1.9, 6.7 Hz, 2H), 7.96 (dd, J=1.9, 6.7 Hz, 2H); HRMS calc'd for M+ 314.0605, found 314.0632. Anal. (C17H14O4S)C, H. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With MMPP In methanol; dichloromethane at 20℃; for 3h; | |
99% | With sulfuric acid; dihydrogen peroxide; acetic acid at 0 - 70℃; for 2h; | 4.1.2. 4-(Methylsulfonyl)acetophenone (8) To a solution of 4-(methylthio)acetophenone (7, 5.5 g, 33 mmol) in glacial acetic acid (15 mL) was added 30% H2O2 (8.5 mL,82.5 mmol), 98% H2SO4 (1 mL, 5.5 mmol) was then added in dropwith cooling to maintain the temperature at 0 °C, the mixture was well stirred over 30 min. The mixture was further stirred at 70 °C for 1.5 h, ice H2O (100 mL) was slowly added, the mixture was well stirred, then filtered and the filtrate was washed with H2O (100 mL), and the filtrate was dried under vacuum to give 4-(methylsulfonyl)acetophenone 8 (6.5 g, 99%). |
98% | With dihydrogen peroxide; Cu2H4O40Te2W8(12-)*(x)H2O*12Na(1+) In acetonitrile at 20℃; for 10h; Sealed tube; |
96% | With phosphoric acid; dihydrogen peroxide In acetic acid for 3h; Reflux; | |
96% | With dihydrogen peroxide In acetonitrile at 40℃; for 0.333333h; | |
96% | With dihydrogen peroxide In ethanol at 20℃; for 24h; | 2 Example 2 This example is the preparation of 4-methylsulfone acetophenone by catalytic oxidation reaction of 4-methylthioacetophenone:10 mg of catalyst, 0.5 mmol of 4-methylthioacetophenone, 300 μL of 30% hydrogen peroxide, and 0.5 mL of ethanol were mixed and stirred at room temperature to react for 24 hours.After the reaction, the catalyst was filtered off using a silica gel column, washed with dichloromethane (3×2 mL), the reaction solution was collected, dried, concentrated under reduced pressure, and subjected to column chromatography (developing solvent: n-hexane:ethyl acetate=1:1) to obtain a white color Target product, yield 96% (94.8 mg). |
95% | With potassium peroxymonosulfate In tetrahydrofuran; water monomer at 25℃; for 2h; | 4-(methylsulfonyl)acetophenone (3) To a solution of 4g of 1 (24mmol) in 20 ml THF, mixture of 20g Oxone in THF and water (1:1) was added and stirred at room temperature for 2 hours. THF was removed under reduced pressure and extracted with CHCl3 (325 ml). The organic layer was washed twice with saturated NaHCO3 solutionand dried over anhydrous Na2SO4. The solvent was evaporated and white precipitate was recrystallized in Ethanol.Yield 95%; white crystalline powder; mp: 128-130C;IR (KBr disk): (cm-1) 11481309 (SO2), 1681 (C=O); LCMS(ESI) m/z: 198.9 (M+1, 100). |
92% | With diethylene glycol dibutyl ether; oxygen at 120℃; for 20h; | |
91% | With 3-chloro-benzenecarboperoxoic acid In dichloromethane Ambient temperature; | |
91% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; 4-methoxyisoquinoline; oxygen; copper(II) sulphate In methanol at 65℃; for 72h; Schlenk technique; Sealed tube; Green chemistry; | 15 Example 15: Preparation of 4-(methylsulfonyl)acetophenone by 4-(methylthio)acetophenone TEMPO (3.9 mg, 0.025 mmol) was added to a 100 mL Schlenk reaction tube in turn. Methanol (1 mL), CuSO4 (4.0 mg, 0.025 mmol), 4-methoxyisoquinoline (39.8 mg, 0.25 mmol), 4-(methylthio)acetophenone (83.1 mg, 0.5 mmol), Filled with 1 atm of oxygen, The sealed reaction tube was heated to 65 ° C for 72 h. After the reaction is completed, it is cooled to room temperature. Add the right amount of ethyl acetate, A blue solid precipitated in the reaction solution. filter, The filtrate was concentrated under reduced pressure. Purification by column chromatography gave the product in a yield of 91%. |
90% | With niobium carbide; dihydrogen peroxide In ethanol; water monomer at 60℃; for 22h; chemoselective reaction; | |
83% | With vanadium pentoxide; 1-methyl-3-dodecylimidazolium hydrogen sulfate; dihydrogen peroxide In water monomer at 20℃; for 6h; | |
83% | With tetra-n-butylammonium tetrafluoroborate; oxygen In dichloromethane at 20℃; for 10h; Electrochemical reaction; Green chemistry; | |
82% | With oxygen; 4C24H20P(1+)*2H(1+)*V10O28(6-) In butanone at 30℃; for 8h; Irradiation; Schlenk technique; | |
82% | With dihydrogen peroxide In water monomer at 75℃; for 2h; | |
82% | With thio-xanthene-9-one; oxygen In butanone at 35 - 40℃; for 24h; Schlenk technique; UV-irradiation; Green chemistry; | 4.1. A typical procedure for the visible-light-promoted aerobic oxidation of sulfides 3 or sulfoxides1 in a ketone solvent General procedure: To a dried Schlenk tube equipped with a stirrer bar which wasevacuated and backfilled with oxygen, were added thioxanthone(10.6 mg, 0.05 mmol, 5.0% mol) and sulfide3 or sulfoxide 1(1.0 mmol), then 5 mL of DEK or MEK was added into the reactiontube via a syringe. The mixture was irradiated by a purple LED lampat 35e40C under oxygen atmosphere (1 atm). After 24 h, thesolvent was removed and the residue was purified by flash column chromatography on silica gel to give the corresponding sulfone2. |
80% | With 1,1,2,2-tetrahydroperoxy-1,2-diphenylethane In tetrahydrofuran at 20℃; for 2.08333h; Green chemistry; chemoselective reaction; | General procedures for selective oxidation of sulfdes tosulfoxides or sulfones General procedure: To a stirred solution of sulfde (1 mmol) and THF (4 mL),THPDPE (1 up to 5.5 mmol (0.310 up to 1.70 g) dependingon the substrates and products) was added and the mixture wasstirred at room temperature for an appropriate time. After completion of the reaction, as monitored by TLC, a saturated aqueous solution of Na2SO3 (2 mL of 1 M solution) was added toquench the excessive oxidant that was remained in the mixture.Water (10 mL) was added to the mixture and extracted usingchloroform (3 × 5 mL) and dried over anhydrous MgSO4. Afterevaporation of solvent under reduced pressure chromatographyon silica gel was used to give pure products. |
80% | With urea-2,2-dihydroperoxypropane In tetrahydrofuran at 20℃; for 2.16667h; Green chemistry; chemoselective reaction; | Typical Procedure for Selective Oxidation of Methyl(phenyl)sulfide Sulfides to (methylsulfinyl)benzene and(methylsulfonyl)benzene General procedure: To a stirred solution of sulfide (1 mmol, 0.124 g) and THF (4 mL), urea-2,2-dihdroperoxypropane (2 or 6 mmol, 0.336-1.00 g pending to products) was added and the mixture was stirred at room temperature for an appropriate time. After completion of the reaction as monitored by TLC, saturated aqueous solution of Na2SO3 (2 mL of 1 M solution) was added to quench the excessive oxidant remaining in the mixture. Then water (10 mL) was added to the mixture and extracted using chloroform (3 × 5 mL) and dried over anhydrous MgSO4. After evaporation of solvent under reduced pressure, chromatography on silica gel was used to give pure products. |
79% | With potassium peroxomonosulfate In tetrahydrofuran; methanol; water monomer at 25℃; for 15h; | |
79% | With diethylene glycol dibutyl ether; oxygen; sodium trifluoro-methanesulfinate at 20℃; for 48h; Irradiation; | |
75% | With diethylene glycol dibutyl ether; oxygen at 150℃; Green chemistry; | |
73% | With anhydrous potassium sulfate; sulfuric acid potassium salt; potassium peroxomonosulfate In water monomer; acetone cooling; | |
72% | With oxygen at 100℃; for 20h; Schlenk technique; chemoselective reaction; | |
68% | With hydrogenchloride; tetra-n-butylammonium perchlorate; oxygen In water monomer; acetonitrile for 0.166667h; Electrochemical reaction; Flow reactor; Green chemistry; | |
64% | With tetra-n-butylammonium perchlorate; water monomer; oxygen In acetonitrile at 20℃; for 3h; Electrochemical reaction; | |
60% | With 1,1,1,3',3',3'-hexafluoro-propanol; water monomer; lithium perchlorate; acetic acid at 20℃; for 8h; Electrochemical reaction; chemoselective reaction; | |
31% | With tetra-n-butylammonium tetrafluoroborate; water monomer In methanol at 25℃; for 10h; Electrochemical reaction; | |
With potassium permanganate; acetic acid | ||
With phosphoric acid; dihydrogen peroxide; acetic acid | ||
With potassium permanganate; acetic acid | ||
With potassium permanganate; acetic acid In water monomer at 60 - 70℃; | ||
With potassium peroxomonosulfate In tetrahydrofuran; methanol at 25℃; for 15h; | ||
With potassium permanganate; acetic acid; anhydrous sodium sulphite In water monomer | 2.d 4-(Methylsulfonyl)acetophenone EXAMPLE 2d 4-(Methylsulfonyl)acetophenone A solution of 152 g (0.96 mol) of KMnO4 in 3.5 1 of water is introduced into a mixture of 117.1 g (0.7 mol) of 4-(methylthio)acetophenone, prepared in Example 2c, and 292 ml of acetic acid. 2.3 l of water are added and the reaction temperature is allowed to return to room temperature. Saturated sodium sulfite solution is added dropwise until the solution is decolorized. This is left to stand overnight at room temperature. The solid obtained is filtered off, washed copiously with water and recrystallized from 95% ethanol to give 91.5 g of 4-(methylsulfonyl)acetophenone. Empirical formula: C9 H10 O3 S; Melting point: 126° C. The compound of Example 3 was prepared by following the procedure of Examples 2c and 2d using the appropriate acid chloride. | |
With sodium wolframate; sulfuric acid; dihydrogen peroxide In water monomer; 1,2-dichloro-benzene at 45℃; for 1h; | Preparation of Ketosulfone 4 A 1 L 3-neck round bottom flask equipped with a mechanical stirrer, temperature probe, addition funnel, and N2 inlet was charged with sodium tungstate dihydrate (1.0g as a solution in 20 ml H2O), sulfuric acid (1M, 4 mL), ketosulfide solution (1L of an o-DCB solution, 98g, 1 equiv.) and Aliquat 336. The mixture was heated under a nitrogen atmosphere to 45°C. An addition funnel was charged with 150 ml aqueous 30% hydrogen peroxide and 15 ml was added to the ketosulfide-Na2WO4 mixture. The reaction was aged for 15 minutes and sampled. The remainder of the hydrogen peroxide (135 ml) was added over 1 hour at a temperature of 45°C. The reaction was aged for 30 minutes and assayed. The mixture was cooled to 18°C. The unreacted peroxide was quenched by the slow addition of aqueous 20 wt% sodium bisulfite solution. The temperature was maintained under 25 °C The mixture was aged for 30 min at 22°C and was then filtered. The wet cake was washed once with H2O (100 mL) and once with IPA (300 ml) and was then dried in vacuo at 40°C (nitrogen sweep) to give 104.7 g of ketosulfone (89.6% yield from thioanisole). | |
With magnesium bis(monoperoxyphthalate) In methanol; dichloromethane at 20℃; for 3.5h; | 1 A solution of 197 g of 4-(methylthio)acetophenone (ref: JACS, 1952, 74, p. 5475) in 700 mL of MeOH and 3500mL of CH2Cl2 was added 881 g of MMPP over a period of 30 min. After 3 h at room temperature the reaction mixture was filtered and the filtrate was washed with 2 L of saturated aqueous solution of NaHCO3 and 1 L of brine. The aqueous phase was further extracted with 2 L of CH2Cl2. The combined extracts was dried over Na2SO4 concentrated to give 240 g of 4(methylsulfonyl)acetophenone as a white solid. To a cooled (-5° C.) solution of 174 g of 4(methylsulfonyl)acetophenone in 2.5 L of CHCl3 was added 20 mg of AlCl3, followed by a solution of 40 mL of Br2 in 300 mL CHCl3. The reaction mixture was then treated with 1.5 L of water and the CHCl3 was separated. The aqueous layer was extracted with 1 L of EtOAc. The combined extracts was dried over Na2SO4 and concentrated. The crude product was recrystalized from 50/50 EtOAc/hexane to give 210 g of 2-bromo-1-(4-(methylsulfonyl)phenyl)ethanone as a white solid. | |
With magnesium bis(monoperoxyphthalate) In methanol; dichloromethane | 6 FIG. 7 outlines the synthesis of a no-carrier-added iodine-123 labeled analogue of rofecoxib 1. Thioanisole 2 was converted to the requisite potassium trifluoroboronate salt 8 in six steps. Ketone 3 was prepared by Friedel-Crafts acylation of thioanisole 2. Oxidation of 3 using MMPP (magnesium monoperoxyphthalate hexahydrate) afforded sulfone 4 which was allowed to react with bromine in chloroform at 0° C. in the presence of a trace amount of AlCl3 to generate 5. Bromoketone 5 was then coupled with 4-iodophenylacetic acid and then cyclized in the presence of triethylamine and DBU to produce 6 (the non radioactive analogue of the target molecule 1) in 52% yield. Compound 6 was converted to boronic ester 7 using Suzuki chemistry. Addition of KHF2 then generated the trifluoroborate 8. Compound 8 was then reacted according to the method of the invention to generate the no-carrier-added radioiodinated 1. The radiochemical purity of the product exceeded 98% as revealed by radio TLC and the radiochemical yield was 42%. | |
With Mo-DAPSH(at)APTES(at)SiO2; dihydrogen peroxide In water monomer at 20℃; for 0.5h; | ||
With ammonium heptamolybdate tetrahydrate; dihydrogen peroxide In methanol; water monomer at 20℃; | ||
With potassium peroxymonosulfate In tetrahydrofuran; water monomer | ||
With water monomer In 1,4-dioxane for 12h; Reflux; | ||
Multi-step reaction with 2 steps 1: potassium peroxymonosulfate / ethanol / 12 h / 60 °C 2: thio-xanthene-9-one; oxygen / pentan-3-one / 35 - 40 °C / 760.05 Torr / Schlenk technique; UV-irradiation; Green chemistry |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91.7% | With bromine In chloroform; water at 50 - 55℃; for 0.25h; | 1-2 Preparation of α,α-dibromo-4-methanesulfonylacetophenone represented by formula II of Example 1 19.8 g of 4-methanesulfonylacetophenone was dissolved in 100 ml of chloroform.35.2 g of bromine was slowly added dropwise at 50-55 ° C, and the reaction was incubated for 15 min after the addition.Cool, control 0-5 ° C and add 100 ml of water.The organic layer was dried over anhydrous sodium sulfate and concentrated to dryness.Add 50 ml of ethyl acetate, heat to reflux for 2 h, cool to 10-15 ° C for 2 h,Filtered and dried to obtain 32.6 g of α,α-dibromo-4-methanesulfonylacetophenone.The yield was 91.7% and the purity was 98.3%. |
With bromine; acetic acid | ||
With bromine In acetic acid at 40℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94.4% | With bromine In chloroform at 34 - 36℃; for 0.25h; | 2.2-1 4-methanesulfonylacetophenone (5.0 g) was added to 40 ml of chloroform. A solution of bromine (4.1 g) in chloroform (10 ml) was slowly added dropwise at 34-36 °C. The reaction was continued for 15 min after the completion of the dropwise addition, and the reaction was completed. The aqueous layer was added, and the organic layer was dried over anhydrous sodium sulfate and evaporated. The resulting solid was beaten with ethyl acetate and filtered. The mixture was dried to obtain 6.6 g of α-bromo-4-methanesulfonylacetophenone, the yield was 94.4%, and the purity was 98.5%. |
93% | With bromine; acetic acid at 20℃; | Bromination The direct bromination of the ketosulfone 4 with bromine in HOAc, initiated with HBr and carried out at ambient temperature, gave a 93% conversion to 2-bromo-4-(methylsulfonyl)acetophenone 2 (herein on referred to as bromoketone 2). [12.1] 0.96-0.98 equivalents of bromine relative to ketosulfone results in a 93% conversion to bromoketone. Further addition of bromine tends to increase amounts of dibromoketone. The bromination reaction has an induction period ranging from 1-15 minutes on average. The reaction is exothermic and is preferably controlled to 25 to 24°C. Addition of water (1 vol) to the slurry in HOAc followed by filtration provided an 87% yield of bromoketone 2. Brominations in acetic acid carried out at preferably 22-24°C at concentrations ranging from 3-10 ml acetic acid per gram of ketosulfone. |
89% | With N-Bromosuccinimide; toluene-4-sulfonic acid In acetonitrile at 80℃; | 4.1 General procedure for the synthesis of 2-bromo-1-substituted phenylethanone 10a-10i General procedure: A modified reaction route: NBS (1.2 equiv.) was added to a solution of appropriately substitutedacetophenones 9a-9l (1.0 equiv.) in CH3CN (15 mL) with p-TSA (0.2 equiv.). The solution washeated at 80 °C for 3-5 h until all the starting materials had been consumed (TLC monitored). Thereaction mass was poured in ice-cold water and extracted with DCM (3 × 20 mL). Anhydrous Na2SO4was added to the combined organic layer, filtered and the excess solvent was removed under reducedpressure. The resultant solid/ liquid obtained were washed with hexane to yield compounds 10a-10i.4,5 |
87% | With bromine In chloroform | 29 EXAMPLE 292-Bromo-l-(4-methanesuIfonyl-phenyl)-ethanone): To a solution of l-(4- Methanesulfonyl-phenyl)-ethanone (25 g, 0.12 mol) in 500 mL chloroform was added , drop-wise, bromine (19.2 g, 0.12 mol) in 60 mL chloroform over a period of 3 h. The mixture was stirred over night. Water (200 mL) was carefully added to the reaction mixture, mixed well and the organic layer isolated was washed with saturated sodium hydrogen carbonate in water (200 mL), followed by brine (200 mL), dried over anhydrous sodium sulfate, filtered and filtrate evaporated to get pure product as a light yellow powder (32 g, 87%) |
87% | With hydrogen bromide; bromine; acetic acid In water at 20 - 25℃; for 2 - 3h; | Synthesis of Bromoketone 2 2 L 3-neck round bottom flask equipped with a mechanical stirrer, temperature probe, addition funnel, and N2 inlet was charged with glacial acetic acid, ketosulfone and aq. 48% HBr. An addition funnel was charged with bromine. A 10% (8.1 g) charge of bromine gave an orange slurry which was aged 30 min at 25°C and was then sampled. The bromination reaction has an induction period of 1-15 min after which bromine was rapidly consumed as it was added. The remainder of the bromine was added over 50 min at 20-25°C. The resulting pale yellow slurry was aged for 2 h at 22-25°C. After ageing the mixture for 2-3 h the batch was filtered. The wet cake was washed once with 200 mL of 1:1 H2O:HOAc and once with H2O (200 mL). The cake was dried in vacuo at 40°C with a N2 sweep to give 126.0 g of bromoketone (87%). |
86% | With aluminium trichloride; bromine In chloroform at -5℃; | |
85% | Stage #1: 4-(methanesulfonyl)acetophenone With hydrogen bromide; acetic acid at 20℃; for 0.0833333h; Stage #2: With bromine at 25 - 58℃; for 2.5h; | 4.1.3. 2-Bromo-1-(4-(methylsulfonyl)phenyl)ethanone (9) To a solution of 4-(methylsulfonyl)acetophenone (8, 2.0 g,0.01 mol) in glacial acetic acid (10 mL) at r.t. was added 48% HBr a drop, well stirred over 5 min, followed by a solution of bromine (0.5 mL, 0.01 mol) dissolved in 5 mL glacial acetic acid was added indrop about 0.5 mL, the solution was orange yellow, raise the temperature to 58 °C, after 0.5 h the solution changed to white. Then it was cooled to 25 °C and the remaining bromine and glacial acid solution was added in drop. The mixture was stirred for 2 h, after completion of the reaction, ice H2O (100 mL) was added and solid precipitated then filtered and the filtrate was dried under vacuum to give 2.35 g of 5 (85%). |
83% | With bromine In chloroform at 20℃; | α-bromo-4-(methylsulfonyl)acetophenone (4) Dissolve 2g (10.1 mmol) of 2 in 20 ml CHCl3. The brominewas added drop wise. After the reaction was completed(monitored by TLC), the solvent was evaporated under reducedpressure and the precipitate was recrystallized inEthanol. Yield 83%; white crystalline powder; mp: 125-127C; IR (KBr disk): (cm-1) 1165, 1308 (SO2), 1710(C=O); LC-MS (ESI) m/z: 276.7 (M+1, 100). |
77% | With bromine In chloroform at -5℃; for 1h; | |
73% | With acetic acid In dichloromethane at 20℃; | |
66% | With bromine In chloroform at 15℃; for 1h; | 215.1 2-Bromo-1-(4-(methylsulfonyl)phenyl)ethanone To the solution of 1-(4-(methylsulfonyl)phenyl)ethan-1-one (5.00 g, 25.2 mmol) inCHCI3 (100 mL) was added Br2 (4.0 0 g, 25.2 mmol) in CHCI3 (15 mL) dropwiseover period of 1 h, the mixture was stirred for 1 h at RT (15 00). The solution was washed with saturated NaHCO3 (30 mL) and brine (30 mL), dried over Na2504. After removal of solvent under reduced pressure, the crude product was recrystallized from EtOH (50 mL) at RT to afford a white solid as product 20 (4.60g, 16.6 mmol, 66 %). 1H NMR (300 MHz, CDCI3): O = 3.12 (5, 3 H), 4.48 (5, 2 H),8.10 (m, 2 H), 8.18 (m, 2 H) ppm. |
66% | With bromine In chloroform at 15℃; | 661.1 Step 1 : 2-Bromo-1-(4-(methylsulfonyl)phenyl)ethanone Step 1 : 2-Bromo-1-(4-(methylsulfonyl)phenyl)ethanone To the solution of 1-(4-(methylsulfonyl)phenyl)ethan-1-one (5.00 g, 25.2 mmol) in CHCIs (100 mL) was added Br2 (4.0 0 g, 25.2 mmol) in CHCI3 (15 mL) dropwise over period of 1 h, the mixture was stirred for 1 h at RT (15 °C). The solution was washed with saturated NaHC03 (30 mL) and brine (30 mL), dried over Na2S04. After removal of solvent under reduced pressure, the crude product was recrystallized from EtOH (50 mL) at RT to afford a white solid as product 20 (4.60 g, 16.6 mmol, 66 %). 1 H NMR (300 MHz, CDCI3): δ = 3.12 (s, 3 H), 4.48 (s, 2 H), 8.10 (m, 2 H), 8.18 (m, 2 H) ppm. |
60% | With N-Bromosuccinimide; toluene-4-sulfonic acid In acetonitrile at 50℃; for 24h; | 25.1 Step 1: Compound P025-b At room temperature, compound P025-a (5.00 g, 25.25 mmol, 1.00 eq.),N-bromosuccinimide (NBS) (4.587g, 25.57mmol, 1.02eq.) and p-toluenesulfonic acid monohydrate (4.80g, 25.25mmol, 1.00eq.) are dissolved in anhydrous acetonitrile (15.00 mL, 3.00eqv.) at 50°C for 24 hours. The reaction solution was concentrated under reduced pressure, mixed with 40 mL of saturated sodium bicarbonate solution, extracted with dichloromethane (30 mL×3), combined the organic phases, washed with water until neutral, washed with saturated brine, dried with anhydrous sodium sulfate, filtered, Concentrate under reduced pressure to obtain crude product. The crude product was purified by silica gel chromatography column (petroleum ether: ethyl acetate=95:5) to obtain compound P025-b. Yield: 60%; |
With bromine; acetic acid | ||
With chloroform; bromine | ||
15.7 g | With hydrogenchloride; bromine In acetic acid | |
With hydrogenchloride; bromine In acetic acid; pentane | 2 2-bromo-1-(4-methanesulphonylphenyl)-ethanone EXAMPLE 2 2-bromo-1-(4-methanesulphonylphenyl)-ethanone 38.5 ml of bromine dissolved in 110 ml of acetic acid are added dropwise onto a suspension of 159 g of the product of Example 1 in 1.6 l of acetic acid and 1.6 ml of hydrochloric acid, the reaction mixture is then stirred for 3 h at ambient temperature. The precipitate obtained is filtered, rinsed with water and then dissolved in dichloromcthane and dried over magnesium sulphate. The dichloromethane is evaporated off, the residue is taken up in pentane and filtered to give 100 g of the expected product. A second batch is obtained by pouring the filtrate of the reaction mixture onto an icc/water mixture, then by filtering off and by treating the precipitate as previously. The two batches are then combined and recrystallized from acetic acid. Yield 143 g, 64%, melting point 130° C. | |
With hydrogenchloride; bromine In water; acetic acid | 1 Stem 3:Preparation of 2-bromo-4'-(methylsulfonyl) acetophenone Stem 3:Preparation of 2-bromo-4'-(methylsulfonyl) acetophenone To a stirred solution of 11.91 g (60.5 mmol) of 4-(methylsulfonyl)acetophenone (prepared in Step 2) in 133 mL of glacial acetic acid and 0.11 mL of hydrochloric acid at ambient temperature was added a solution of 8.22 g (51.4 mmol) of bromine in 9.3 mL of glacial acetic acid over a period of three hours. The reaction mixture was diluted with 500 mL of water and extracted with chloroform. The combined extracts were dried (MgSO4) and concentrated in vacuo to give 15.7 g of crude 2-bromo-(4'-methylsulfonyl)acetophenone as a solid: NMR (CDCl3) δ 3.10 (s, 3H), 4.45 (s, 2H), 8.08 (d, J=9 Hz, 2H), 8.17 (d, J=9 Hz, 2H). | |
With bromine In hexane; chloroform; water; ethyl acetate | 1.1 Step 1 To a cooled (-5° C.) solution of 174 g of 4-(methyl-sulfonyl)acetophenone in 2.5 L of CHCl3 was added 20 mg of AlCl3, followed by a solution of 40 mL of Br2 in 300 mL CHCl3. The reaction mixture was then treated with 1.5 L of water and the CHCl3 was separated. The aqueous layer was extracted with 1 L of EtOAc. The combined extracts was dried over Na2 SO4 and concentrated. The crude product was recystalized from 50/50 EtOAc/hexane to give 210 g of the title compound as a white solid. | |
With hydrogenchloride; bromine In water; acetic acid | 12.3 Preparation of 2-bromo-4'-(methylsulfonyl) acetophenone Step 3 Preparation of 2-bromo-4'-(methylsulfonyl) acetophenone To a stirred solution of 11.91 g (60.5 mmol) of 4-(methylsulfonyl)acetophenone (prepared in Step 2) in 133 mL of glacial acetic acid and 0.11 mL of hydrochloric acid at ambient temperature was added a solution of 8.22 g (51.4 mmol) of bromine in 9.3 mL of glacial acetic acid over a period of three hours. The reaction mixture was diluted with 500 mL of water and extracted with chloroform. The combined extracts were dried (MgSO4) and concentrated in vacuo to give 15.7 g of crude 2-bromo-(4'-methylsulfonyl)acetophenone as a solid: NMR (CDCl3) δ 3.10 (s, 3H), 4.45 (s, 2H), 8.08 (d, J=9 Hz, 2H), 8.17 (d, J=9 Hz, 2H). | |
With aluminum (III) chloride; bromine In chloroform at -5℃; | 1 A solution of 197 g of 4-(methylthio)acetophenone (ref: JACS, 1952, 74, p. 5475) in 700 mL of MeOH and 3500mL of CH2Cl2 was added 881 g of MMPP over a period of 30 min. After 3 h at room temperature the reaction mixture was filtered and the filtrate was washed with 2 L of saturated aqueous solution of NaHCO3 and 1 L of brine. The aqueous phase was further extracted with 2 L of CH2Cl2. The combined extracts was dried over Na2SO4 concentrated to give 240 g of 4(methylsulfonyl)acetophenone as a white solid. To a cooled (-5° C.) solution of 174 g of 4(methylsulfonyl)acetophenone in 2.5 L of CHCl3 was added 20 mg of AlCl3, followed by a solution of 40 mL of Br2 in 300 mL CHCl3. The reaction mixture was then treated with 1.5 L of water and the CHCl3 was separated. The aqueous layer was extracted with 1 L of EtOAc. The combined extracts was dried over Na2SO4 and concentrated. The crude product was recrystalized from 50/50 EtOAc/hexane to give 210 g of 2-bromo-1-(4-(methylsulfonyl)phenyl)ethanone as a white solid. | |
With bromine | ||
With aluminum (III) chloride; bromine In chloroform at 0℃; | 6 FIG. 7 outlines the synthesis of a no-carrier-added iodine-123 labeled analogue of rofecoxib 1. Thioanisole 2 was converted to the requisite potassium trifluoroboronate salt 8 in six steps. Ketone 3 was prepared by Friedel-Crafts acylation of thioanisole 2. Oxidation of 3 using MMPP (magnesium monoperoxyphthalate hexahydrate) afforded sulfone 4 which was allowed to react with bromine in chloroform at 0° C. in the presence of a trace amount of AlCl3 to generate 5. Bromoketone 5 was then coupled with 4-iodophenylacetic acid and then cyclized in the presence of triethylamine and DBU to produce 6 (the non radioactive analogue of the target molecule 1) in 52% yield. Compound 6 was converted to boronic ester 7 using Suzuki chemistry. Addition of KHF2 then generated the trifluoroborate 8. Compound 8 was then reacted according to the method of the invention to generate the no-carrier-added radioiodinated 1. The radiochemical purity of the product exceeded 98% as revealed by radio TLC and the radiochemical yield was 42%. | |
With bromine In tetrahydrofuran at 20℃; for 26h; | 1 1.51 mmol of substituted acetophenone are dissolved in 4 mL of THF in a 20 mL flask, then 1.81 mmol (1.2 eq) of bromine supported on Amberlyst A26 are added to the solution. After 6 hours of reaction, a further 0.1 eq of supported bromine is added then the mixture is stirred for 20 hours at room temperature. The resin is subsequently filtered then washed with THF, the filtrate is evaporated to give the crude reaction products which are purified either by flash chromatography over silica gel or by recrystallisation.- 2-bromo-l-(4-methanesulphonyl-phenyl)-ethanone (Method 1)Method 1 above was used to prepare the aforementioned product. EPO 1H NMR (400 MHz, CDCl3): δ 8.20 (d, 2H, aromatic H); 8.10 (d, 2H, aromatic H); 4.48 (s,2H5 CH2); 3.12 (s, 3H, CH3).MS: 277.4+ (M+H)+Rf= 0.14 (silica, 2/1 hept/AcOEt) | |
With bromine; acetic acid | ||
With bromine; 1,2-dichloro-ethane | ||
With copper(ll) bromide In ethyl acetate Reflux; Sonication; | Preparation of α-Cyanoketones General procedure: 20 mmol of the appropriate acyl ketone was dissolved in 40 mL of ethyl acetate to make a 0.5 M solution. 2.6 equivalents of CuBr2 was added and the mixture refluxed with a condenser for 3-5 h until the starting ketone was fully consumed as indicated by TLC or 1H NMR. Once the reaction was complete, the mixture was cooled, and then the ethyl acetate was removed under reduced pressure. Hexanes were added to the crude solid and the mixture was sonicated for 5 min. The hexanes were decanted and a fresh volume was added to the remaining solids, again sonicating for 5min. This process was repeated once more, for a total of 3 extractions. The combined hexane layers, which typically appeared as an amber or light yellow solution, were evaporated under reduced pressure to yield the crude product which typically appeared as yellow or orange oil. If a sonicator is not available, a Soxhlet extraction with hexanes gives similar yields. The crude bromoketone oil was next dissolved in a 5:1 mixture of ethanol/water to give a 0.4 M solution overall. The solution was cooled over ice, and then 3 equivalents of NaCN were added. The reaction was stirred overnight (16 h), allowing the ice to melt. The solution was then diluted with enough water to roughly double the initial volume. This solution was filtered through a Celite pad to remove suspended solids. This solution was then acidified by adding concentrated HCl to a stirring solution. CAUTION This will cause the evolution of HCN gas Only perform in a well-ventilated fume hood The acidified solution was allowed to stir for 15 minutes. The solution was checked by pH paper to ensure that it was acidic (pH ≤ 2). If not, additional HCl was added, taking the same precautions noted above. Once the solution was acidic, it was transferred to a separatory funnel and extracted 3x with DCM. The organic layers were combined, dried over magnesium sulfate, filtered, and then evaporated under reduced pressure to obtain the final product. Purity was confirmed by 1H NMR. If significant impurities are observed, the product can be recrystallized, most typically in isopropanol or toluene. | |
With bromine In chloroform at 20℃; | ||
With hydrogen bromide; bromine; acetic acid at 0℃; for 20h; | 4.1.1.1 Synthesis of 2-bromo-1-(4-(methylsulfonyl)phenyl)ethan-1-one (1) Bromine (0.019mol, 1mL) in acetic acid (10mL) was added to a solution of substituted 1-(4-(methylsulfonyl)phenyl)ethan-1-one (0.016mol, 3.168 gr) and 3-5 drops of hydrogen bromide in acetic acid (10mL) at 0°C. The reaction was processed under magnetic stirring for 20h. After completion of the reaction the mixture was poured in an ice-bath, precipitated product was filtered, dried, and recrystallized from EtOH. | |
With copper(ll) bromide In ethyl acetate Reflux; | ||
With N-Bromosuccinimide; toluene-4-sulfonic acid In water; acetonitrile Reflux; | ||
With N-Bromosuccinimide; toluene-4-sulfonic acid In 1,4-dioxane for 6h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With thio-xanthene-9-one; oxygen In pentan-3-one at 35 - 40℃; Schlenk technique; UV-irradiation; Green chemistry; | 4.1. A typical procedure for the visible-light-promoted aerobic oxidation of sulfides 3 or sulfoxides1 in a ketone solvent General procedure: To a dried Schlenk tube equipped with a stirrer bar which wasevacuated and backfilled with oxygen, were added thioxanthone(10.6 mg, 0.05 mmol, 5.0% mol) and sulfide3 or sulfoxide 1(1.0 mmol), then 5 mL of DEK or MEK was added into the reactiontube via a syringe. The mixture was irradiated by a purple LED lampat 35e40C under oxygen atmosphere (1 atm). After 24 h, thesolvent was removed and the residue was purified byflash columnchromatography on silica gel to give the corresponding sulfone2. |
With potassium chromite; anhydrous sodium perchlorate; oxalic acid In acetic acid at 40℃; | ||
With potassium bromate; sulfuric acid; mercury (II) acetate In acetic acid at 35℃; other temperatures, ΔH(excit.), ΔS(excit.); |
With peroxomonophosphoric acid; anhydrous sodium perchlorate In water monomer; acetic acid at 35℃; | ||
With oxo(salen)chromium(V) perchlorate In acetonitrile at 24.85℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94.9% | With copper(l) iodide; N,N-dimethyl-N-benzyl-N-(2-methacryloyloxyethyl)ammonium bromide; caesium carbonate In chlorobenzene at 110℃; for 24h; Inert atmosphere; | 1-2 4-iodoacetophenone (24.6 g), sodium methanesulfonate (20.4 g), N,N-dimethyl-N-[2-(methacryloyloxy)ethyl]-1-benzylammonium bromide (3.3 g, ie, formula I-1), cesium carbonate (65.1 g) and cuprous iodide (1.9 g) was added to 500 ml of chlorobenzene and heated to 110 ± 2 ° C for 24 hours under nitrogen atmosphere. After completion of the reaction, the reaction solvent was concentrated under reduced pressure. Add water and methylene chloride to dissolve, add decolorization by activated carbon adsorption, and filter with a small amount of diatomaceous earth. The layers were separated and the methylene chloride layer was dried over anhydrous sodium sulfate and evaporated. Add ethanol to beat, filter, drying gave 18.8 g of 4-methanesulfonylacetophenone, the yield was 94.9%, and the purity was 98.4%. |
83% | With potassium phosphate; copper(l) iodide; (2S,4R)-N-(2,6-dimethylphenyl)-4-hydroxypyrrolidine-2-carboxamide In dimethyl sulfoxide at 20℃; for 24h; Inert atmosphere; | |
80% | With copper(l) iodide; sodium L-prolinate In dimethyl sulfoxide at 80℃; for 24h; |
With copper(I) trifluoromethanesulfonate benzene; N,N`-dimethylethylenediamine In dimethyl sulfoxide at 110℃; for 20h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With copper diacetate; 4 Angstroem MS; potassium carbonate In dimethyl sulfoxide at 20 - 60℃; for 16h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With potassium phosphate; copper(l) iodide; (2S,4R)-N-(2,6-dimethylphenyl)-4-hydroxypyrrolidine-2-carboxamide In dimethyl sulfoxide at 90℃; for 24h; Inert atmosphere; | |
62% | With copper(l) iodide; sodium L-prolinate In dimethyl sulfoxide at 95℃; for 48h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 94% 2: 2% | With boron trifluoride diethyl etherate In acetonitrile for 0.0833333h; cooling; | |
1: 67% 2: 9% | With oxygen at 80℃; for 20h; chemoselective reaction; | |
1: 65% 2: 11 %Chromat. | With oxygen; 4C24H20P(1+)*2H(1+)*V10O28(6-) In water; butanone at 30℃; for 2h; Irradiation; Schlenk technique; |
With dihydrogen peroxide In acetonitrile; <i>tert</i>-butyl alcohol at 19.85℃; for 8h; | ||
With dihydrogen peroxide In water; acetonitrile at 19.84℃; for 2h; | ||
With dihydrogen peroxide In water; acetonitrile at 19.84℃; for 2h; chemoselective reaction; | ||
1: 65 %Chromat. 2: 14 %Chromat. | With (tetra-n-butylammonium)6[(PW10O36)2Ti4O2(OH)4]*EtOAc*H2O; dihydrogen peroxide In water; acetonitrile at 31.84℃; for 0.0833333h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | In methanol at 25℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | In methanol at 25℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | In methanol at 25℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | In methanol at 25℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | The synthesis was carried out as described in Scheme 2. Step a. A mixture of 4-(methylsulfonyl)acetophenone (5.5 g, 27.8 mmol), morpholine (2.5 mL), and sulfur (0.89 g, 27.8 mmol) was refluxed for 10 h, and poured into ice. The precipitated solid was filtered, and washed with cold ethyl acetate. The solid was added to 10% sodium hydroxide (55 mL), heated to 84 C. for 12 h, and the alkaline solution was acidified with 12 N HCl. The resulting solid was filtered, dried, and recrystallized from hexane-ethyl acetate (1:1) to give 4-methylsulfonylphenylacetic acid (white solid, 4.2 g, 52% overall yield). Step b. 2-Bromoacetophenone (1.02 g, 5.12 mmol), dissolved in acetonitrile, was added to Et3N (1.74 mL), followed by 4-methylsulfonylphenylacetic acid (1 g, 4.67 mmol). After 1.5 h at room temperature, 1,8-diazabicyclo[5,4,0]undec-7-ene (1.67 mL) was added. The reaction mixture was stirred for another 1 h, and then treated with 1 N HCl (35 mL). The product was extracted with ethyl acetate, dried over sodium sulfate, and recrystallized from ethyl acetate-hexane (1:1) to give 46b (880 mg, 60% overall yield). 1H NMR (CDCl3) delta 3.08 (s, 3H), 5.24 (s, 2H), 7.18-7.30 (m, 5H), 7.66 (dd, J=1.9, 6.7 Hz, 2H), 7.96 (dd, J=1.9, 6.7 Hz, 2H); HRMS calc'd for M+ 314.0605, found 314.0632. Anal. (C17H14O4S)C, H. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With C37H40MnN2O2P2(1+)*Br(1-); sodium t-butanolate In isopropyl alcohol at 50℃; for 3h; Inert atmosphere; Schlenk technique; enantioselective reaction; | |
Stage #1: 4-(methanesulfonyl)acetophenone With (S)-1-methyl-3,3-diphenyl-hexahydropyrrolo[1,2-c][1,3,2]oxazaborole Stage #2: With dimethylsulfide borane complex | 7 EXAMPLE 7 The synthesis of compounds with an alkyl or arylsulfonyl R8 group at the para position started with the corresponding para-substituted acetophenone which was treated as in Example 4, steps 1-6 to obtain the sulfone containing compounds of Example 7 having the formula: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydrogencarbonate; magnesium bis(monoperoxyphthalate) hexahydrate In methanol | 1.1 Step 1 Step 1 2-Bromo-1-(4-(methylsulfonyl)phenyl)ethanone A solution of 197 g of 4-(methylthio)acetophenone (ref: J. Am. Chem. Soc., 1952, 74, p. 5475) in 700 mL of MeOH and 3500 mL of CH2 Cl2 was added 881 g of MMPP over a period of 30 min. After 3 h at r.t. the reaction mixture was filtered and the filtrate was washed with 2 L of saturated aqueous solution of NaHCO3 and 1 L of brine. The aqueous phase was further extracted with 2 L of CH2 Cl2. The combined extracts were dried over Na2 SO4 concentrated to give 240 g of 4-(methylsulfonyl)acetophenone as a white solid. | |
With sodium hydrogencarbonate; magnesium bis(monoperoxyphthalate) hexahydrate In methanol | 1.1 Step 1 Step 1 2-Bromo-1-(4-(methylsulfonyl)phenyl)ethanone A solution of 197 g of 4-(methylthio)acetophenone (ref: JACS, 1952, 74, p. 5475) in 700 mL of MeOH and 3500 mL of CH2 Cl2 was added 881 g of MMPP over a period of 30 min. After 3 h at room temperature the reaction mixture was filtered and the filtrate was washed with 2 L of saturated aqueous solution of NaHCO3 and 1 L of brine. The aqueous phase was further extracted with 2 L of CH2 Cl2. The combined extracts was dried over Na2 SO4 concentrated to give 240 g of 4-(methylsulfonyl)acetophenone as a white solid. | |
With sodium hydrogencarbonate; magnesium bis(monoperoxyphthalate) hexahydrate In methanol | C.1 Step 1: Step 1: 2-Bromo-1-(4-(methylsulfonyl)phenyl)ethanone To a solution of 197 g of 4-(methylthio)acetophenone (ref: JACS, 1952,74, p. 5475) in 700 mL of MeOH and 3500 mL of CH2 Cl2 was added 881 g of MMPP over a period of 30 min. After 3 hr at r.t. the reaction mixture was filtered and the filtrate was washed with 2 L of saturated aqueous solution of NaHCO3 and 1 L of brine. The aqueous phase was further extracted with 2 L of CH2 Cl2. The combined extracts was dried over Na2 SO4 concentrated to give 240 g of 4-(methylsulfonyl)acetophenone as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bromine In hexane; chloroform; ethyl acetate | 1.1 Step 1 To a cooled (-5° C.) solution of 174 g of 4-(methylsulfonyl)-acetophenone in 2.5 L of CHCl3 was added 20 mg of AlCl3, followed by a solution of 40 mL of Br2 in 300 mL CHCl3. The reaction mixture was then treated with 1.5 L of H2 O and the CHCl3 was separated. The aqueous layer was extracted with 1 L of EtOAc. The combined organic extracts were dried over Na2 SO4 and concentrated. The crude product was recystallized from 50/50 EtOAc/hexane to give 210 g of the title compound as a white solid. | |
With bromine In hexane; chloroform; ethyl acetate | C.1 Step 1: To a cooled (-5° C.) solution of 174 g of 4-(methylsulfonyl)acetophenone in 2.5 L of CHCl3 was added 20 mg of AlCl3, followed by a solution of 40 mL of Br2 in 300 mL CHCl3. The reaction mixture was then treated with 1.5 L of H2 O and the CHCl3 was separated. The aqueous layer was extracted with 1 L of EtOAc. The combined extracts were dried over Na2 SO4 and concentrated. The crude product was recystallized from 50/50 EtOAc/hexane to give 210 g of the title compound as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bromine; sodium hydrogencarbonate; magnesium bis(monoperoxyphthalate) hexahydrate In methanol; hexane; chloroform; water; ethyl acetate | 9.1 Step 1 Step 1 2-Bromo-1-(4-(methylsulfonyl)phenyl)ethanone A solution of 197 g of 4-(Methylthio)acetophenone (ref: JACS, 1952, 74, p. 5475) in 700 mL of MeOH and 3500mL of CH2 Cl2 was added 881 g of MMPP over a period of 30 min. After 3 h at room temperature the reaction mixture was filtered and the filtrate was washed with 2 L of saturated aqueous solution of NaHCO3 and 1 L of brine. The aqueous phase was further extracted with 2 L of CH2 Cl2. The combined extracts was dried over Na2 SO4 concentrated to give 240 g of 4(methylsulfonyl)acetophenone as a white solid. To a cooled (-5 ° C.) solution of 174 g of 4(methylsulfonyl)acetophenone in 2.5 L of CHCl3 was added 20 mg of AlCl3, followed by a solution of 40 mL of Br2 in 300 mL CHCl3. The reaction mixture was then treated with 1.5 L of water and the CHCl3 was separated. The aqueous layer was extracted with 1 L of EtOAc. The combined extracts was dried over Na2 SO4 and concentrated. The crude product was recystalized from 50/50 EtOAc/hexane to give 210 g of 2-bromo-1-(4-(methylsulfonyl)phenyl)ethanone as a white solid. | |
With bromine; sodium hydrogencarbonate; magnesium bis(monoperoxyphthalate) hexahydrate In methanol; chloroform; water | 9.1 Step 1 Step 1 2-Bromo-1-(4-(methylsulfonyl)phenyl)ethanone A solution of 197 g of 4-(Methylthio)acetophenone (ref: JACS, 1952, 74, p. 5475) in 700 mL of MeOH and 3500 mL of CH2 Cl2 was added 881 g of MMPP over a period of 30 min. After 3 h at room temperature the reaction mixture was filtered and the filtrate was washed with 2 L of saturated aqueous solution of NaHCO3 and 1 of brine. The aqueous phase was further extracted with 2 L of CH2 Cl2. The combined extracts was dried over Na2 SO4 concentrated to give 240 g of 4-(methylsulfonyl)acetophenone as a white solid. To a cooled (-5° C.) solution of 174 g of 4-(methylsulfonyl)acetophenone in 2.5 L of CHCl3 was added 20 mg of AlCl3, followed by a solution of 40 mL of Br2 in 300 mL CHCl3. The reaction mixture was then treated with 1.5 L of water and the CHCl3 was separated. The aqueous layer was extracted with 1 L of EtOAc. The combined extracts was dried over Na2 SO4 and concentrated. The crude product was recrystallized from 50/50 EtOAc/hexane to give 210 g of 2-bromo-1-(4-(methylsulfonyl)phenyl)ethanone as a white solid. | |
With bromine; sodium hydrogencarbonate; magnesium bis(monoperoxyphthalate) hexahydrate In methanol; hexane; chloroform; water; ethyl acetate | 9.1 Step 1 Step 1 2-Bromo-1-(4-(methylsulfonyl)phenyl)ethanone A solution of 197 g of 4-(Methylthio)acetophenone (ref: JACS, 1952, 74, p. 5475) in 700 mL of MeOH and 3500 mL of CH2 Cl2 was added 881 g of MMPP over a period of 30 min. After 3 h at room temperature the reaction mixture was filtered and the filtrate was washed with 2 L of saturated aqueous solution of NaHCO3 and 1 L of brine. The aqueous phase was further extracted with 2 L of CH2 Cl2. The combined extracts was dried over Na2 SO4 concentrated to give 240 g of 4-(methylsulfonyl)acetophenone as a white solid. To a cooled (-5° C.) solution of 174 g of 4-(methylsulfonyl)acetophenone in 2.5 L of CHCl3 was added 20 mg of AlCl3, followed by a solution of 40 mL of Br2 in 300 mL CHCl3. The reaction mixture was then treated with 1.5 L of water and the CHCl3 was separated. The aqueous layer was extracted with 1 L of EtOAc. The combined extracts was dried over Na2 SO4 and concentrated. The crude product was recystalized from 50/50 EtOAc/hexane to give 210 g of 2-bromo-1-(4-(methylsulfonyl)phenyl)ethanone as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; bromine In water; acetic acid | 1.3 Preparation of 2-bromo-4'-(methylsulfonyl)acetoohenone Step 3 Preparation of 2-bromo-4'-(methylsulfonyl)acetoohenone To a stirred solution of 11.91 g (60.5 mmol) of 4-(methylsulfonyl)acetophenone (prepared in Step 2) in 133 mL of glacial acetic acid and 0.11 mL of hydrochloric acid at ambient temperature was added a solution of 8.22 g (51.4 mmol) of bromine in 9.3 mL of glacial acetic acid over a period of three hours. The reaction mixture was diluted with 500 mL of water and extracted with chloroform. The combined extracts were dried (MgSO4) and concentrated in vacuo to give 15.7 g of crude 2-bromo-(4'-methylsulfonyl) acetophenone as a solid: NMR (CDCl3) δ 3.10 (s, 3H), 4.45 (s, 2H), 8.08 (d, J=9 Hz, 2H), 8.17 (d, J=9 Hz, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11.91 g (91%) | With m-chloroperoxybenzoic acid In dichloromethane | 16.2 Step 2 Step 2 Preparation of 4-(methylsulfonyl)acetophenone To a solution of 11.73 g (71.1 mmol) of 4-(methylthio)acetophenone (prepared in Step 1) in 500 mL of dichloromethane at ambient temperature was added 61.14 g (177 mmol) of m-chloroperoxybenzoic acid (50%) (MCPBA) in portions over 20 minutes. The reaction was stirred for two hours, quenched slowly with aqueous sodium bisulfite, washed with three 100 mL portions of saturated sodium bicarbonate, dried (MgSO4), and concentrated in vacuo to give 11.91 g (91%) of (4-methylsulfonyl)acetophenone as an colorless solid: NMR (CDCl3) δ2.67 (s, 3H), 3.08 (s, 3H), 8.06 (d, J=9 Hz, 2H), 8.14 (d, J=9 Hz, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11.91 g (91%) | With m-chloroperoxybenzoic acid In dichloromethane; 4-(Methylthio)acetophenone | 13.2 Preparation of 4-(methylsulfonyl)acetophenone Step 2 Preparation of 4-(methylsulfonyl)acetophenone To a solution of the acetophenone prepared in Step 1 (11.73 g, 71.1 mmol) in dichloromethane (500 ml) at ambient temperature was added m-chloroperoxybenzoic acid (50%, 61.14 g, 177 mmol) in portions; over 20 minutes. The reaction was stirred for two hours, quenched slowly with sodium, meta-sulfide washed with three 100 ml portions of saturated sodium, bicarbonate, dried (MgSO4), and concentrated in vacuo to give 11.91 g (91%) of 4-(methylsulfonyl)acetophenone as an off-white solid: 1H NMR (CDCl3) δ 2.67 (s, 3H), 3.08 (s, 3H), 8.06 (d, Hz, 2H), 8.14 (d, J=9 Hz, 2H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: phenylacetic acid With isopropylmagnesium bromide In tetrahydrofuran at -78 - 40℃; for 0.5h; Stage #2: 4-(methanesulfonyl)acetophenone In tetrahydrofuran at -78 - 40℃; for 0.5h; Stage #3: methanol With hydrogenchloride; phosphorus pentoxide; potassium carbonate more than 3 stages; | 1.1 Step 1: methyl(2E)-3-[4-(methylsulfonyl)phenyl]-2-phenylbut-2-enoate [AT-78 °C,] 15 mL of isopropylmagnesium bromide (30 mmol, 2M) was added dropwise to a solution of 15 mmol of phenyl-acetic acid in 4 mL [OF THF.] The mixture was then warmed to [40 °C] and stirred for 30 min and then re-cooled to- [78 °C.] A solution of 15 mmol of [1- (4-METHANESULFONYL-PHENYL)-ETHANONE] in a minimum amount of THF was added to the reaction mixture. The resulting mixture was warmed again to [40 °C FOR] 30 min, and then the reaction was quenched by the addition of 35 mL of 1 M [HC1.] The organic layer was separated and washed with brine. The aqueous layer was extracted with EtOAc and the organic layer was dried over [NA2S04] and filtered. The filtrate was treated with CH2N2/Et2O until TLC analysis revealed the absence of the carboxylic acid. The solvent was evaporated and the residue was dissolved in 100 mL of 1,2-dichloroethane and refluxed with 4 g [OF P205 FOR] 40 min. The reaction mixture was cooled to room temperature and filtered through a pad of silica gel. The solid was washed thoroughly with EtOAc. The filtrate was evaporated and the residue was dissolved in 100 mL [OF MEOH] and stirred at rt with 4 g [OF K2C03] overnight. The solvent was evaporated and the residue was treated with [H20] and extracted with EtOAc. The organic layer was dried over [NA2S04] and evaporated to afford 3.4 g of a mixture of [(2E)-AND (2Z)-3- (4-] methanesulfonyl-phenyl)-2-phenyl-but-2-enoic acid methyl ester in about a 1: 1 ratio according to [1H] NMR analysis. The two isomers were separated by flash chromatography to afforded 634 mg of methyl [(2E)-3- [4- (METHYLSULFONYL) PHENYL]-2-] [PHENYLBUT-2-ENOATE. IH NMR (ACETONE-D6,] 500 MHz): [5] 7.47 (dd, J = 6. 7,1. 9 Hz, 2 H), 7.36 (dd, [J=6.] 7,1. 9 Hz, 2 H), 7. [16-7. 10] (m, [3 H),] 7.06-6. 98 (m, 2 H), 3.75 (s, 3 H), 3.04 (s, 3 H), 2.34 (s, 3 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With barium hydroxide octahydrate In methanol at 40℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With sulfur at 75℃; for 3h; | 2 Example 2 Preparation of 2-(4-Methylsulfonyl)phenyl)-1-morpholinoethanethiol The 4-methanesulfonylacetophenone (10 g, 50 mmol) was sequentially added to the four-vial flask. Sublimed sulfur (1.9g, 60mmol), HBF4 · Si02 Powder (5g, 2.5mmol) And morpholine (5.3mL, 60mmol), Stir and warm up to 75 °C and react for 3 h. After adding 50 mL of ethyl acetate, the reaction mixture was filtered while hot and the catalyst was removed. The filtrate was again evaporated under reduced pressure, 50 mL of methanol was added, and the crystals were stirred and stirred at room temperature. After suction filtration, 13.3 g of a yellow solid powder was obtained with a yield of 88.0% and a purity of 99.3%, which was directly used in the next hydrolysis step without purification. |
60% | With toluene-4-sulfonic acid; sulfur for 3h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With sodium acetate In ethanol; water for 2h; Reflux; | 4.1 [1] A mixture of 4-sulfonyl acetophenone 1.000g (5.0mmol), methoxy amine hydrochloride 0.835g (10.0mmol), anhydrous sodium acetate 1.640g (20.0mmol), 10ml of ethanol and 30ml water was added 100ml flask.After the reaction mixture was heated to reflux for 2 hours the reaction monitored by TLC After completion, diluted with 15ml of ethyl acetate, and extracted, the organic phase was dried under reduced pressure to remove the solvent, to give 4-sulfonyl oxime ether 0.953g (84% yield rate). |
In methanol; water for 18h; Reflux; | ||
With pyridine In ethanol at 60℃; for 6h; |
With sodium acetate In ethanol; water at 70℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
34% | With barium hydroxide octahydrate In ethanol at 30℃; for 24h; | |
Stage #1: 4-(methanesulfonyl)acetophenone With sodium hydroxide In ethanol at 20℃; for 0.5h; Stage #2: 4-methyl-benzaldehyde In ethanol for 4h; | 3.2.1. General Procedure for Synthesis of Chalcones 3 and7 General procedure: Chalcones were synthesized via clasien-schmidt condensationof substituted benzaldehyde and acetophenones. For 3:4-substituted-acetophenone 2 (5 mmol) and for 7: 1-(4-(methylsulfonyl) phenyl)ethanone 5 (5 mmol), was dissolvedin 20 ml ethanol. NaOH pellet (10 mmol) was added to thissolution and stirred for 30 min at room temperature. Afterthat for 3: 4-(methylsulfonyl)benzaldehyde 1 (5 mmol) andfor 7: 4-substituted-benzaldehyde 6 (5 mmol) was added tothis solution and the stirring continued for 4 h. After completionof reaction, the solvent was evaporated and residuewas extracted with ethyl acetate and water. The purity ofcompounds was monitored by TLC using different solvents with different polarity. The organic layer was separated andevaporated under vacuum on a rotary evaporator and crystallizedby EtOH. No significant impurity was observed. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
27% | With barium hydroxide octahydrate In ethanol at 30℃; for 24h; | |
With sodium hydroxide In ethanol; water at 20℃; for 10h; | 3.2.1. 3-(4-Substituted phenyl)-1-[4-(methylsulfonyl)phenyl]-2-propen-1-ones 1a-c General procedure: A mixture of 4'-(methylsulfonyl)acetophenone (0.05 mol), aromatic aldehyde (0.05 mol) and 10% aqueous sodium hydroxide (10 mL) in ethanol (30 mL) was stirred at room temperature for 10 h. The progress of the reaction was checked by TLC. Upon completion, the reaction mixture was poured into crushed ice. The precipitated solid was filtered, washed with water, and dried. The product was crystallized from ethanol [18]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With barium hydroxide octahydrate In ethanol at 30℃; for 24h; | |
With sodium hydroxide In ethanol; water at 20℃; for 10h; | 3.2.1. 3-(4-Substituted phenyl)-1-[4-(methylsulfonyl)phenyl]-2-propen-1-ones 1a-c General procedure: A mixture of 4'-(methylsulfonyl)acetophenone (0.05 mol), aromatic aldehyde (0.05 mol) and 10% aqueous sodium hydroxide (10 mL) in ethanol (30 mL) was stirred at room temperature for 10 h. The progress of the reaction was checked by TLC. Upon completion, the reaction mixture was poured into crushed ice. The precipitated solid was filtered, washed with water, and dried. The product was crystallized from ethanol [18]. | |
Stage #1: 4-(methanesulfonyl)acetophenone With sodium hydroxide In ethanol at 20℃; for 0.5h; Stage #2: 4-chlorobenzaldehyde In ethanol for 4h; | 3.2.1. General Procedure for Synthesis of Chalcones 3 and7 General procedure: Chalcones were synthesized via clasien-schmidt condensationof substituted benzaldehyde and acetophenones. For 3:4-substituted-acetophenone 2 (5 mmol) and for 7: 1-(4-(methylsulfonyl) phenyl)ethanone 5 (5 mmol), was dissolvedin 20 ml ethanol. NaOH pellet (10 mmol) was added to thissolution and stirred for 30 min at room temperature. Afterthat for 3: 4-(methylsulfonyl)benzaldehyde 1 (5 mmol) andfor 7: 4-substituted-benzaldehyde 6 (5 mmol) was added tothis solution and the stirring continued for 4 h. After completionof reaction, the solvent was evaporated and residuewas extracted with ethyl acetate and water. The purity ofcompounds was monitored by TLC using different solvents with different polarity. The organic layer was separated andevaporated under vacuum on a rotary evaporator and crystallizedby EtOH. No significant impurity was observed. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With barium hydroxide octahydrate In ethanol at 30℃; for 24h; | |
Stage #1: 4-(methanesulfonyl)acetophenone With sodium hydroxide In ethanol at 20℃; for 0.5h; Stage #2: benzaldehyde In ethanol for 4h; | 3.2.1. General Procedure for Synthesis of Chalcones 3 and7 General procedure: Chalcones were synthesized via clasien-schmidt condensationof substituted benzaldehyde and acetophenones. For 3:4-substituted-acetophenone 2 (5 mmol) and for 7: 1-(4-(methylsulfonyl) phenyl)ethanone 5 (5 mmol), was dissolvedin 20 ml ethanol. NaOH pellet (10 mmol) was added to thissolution and stirred for 30 min at room temperature. Afterthat for 3: 4-(methylsulfonyl)benzaldehyde 1 (5 mmol) andfor 7: 4-substituted-benzaldehyde 6 (5 mmol) was added tothis solution and the stirring continued for 4 h. After completionof reaction, the solvent was evaporated and residuewas extracted with ethyl acetate and water. The purity ofcompounds was monitored by TLC using different solvents with different polarity. The organic layer was separated andevaporated under vacuum on a rotary evaporator and crystallizedby EtOH. No significant impurity was observed. | |
With sodium hydroxide In ethanol; lithium hydroxide monohydrate at 0 - 20℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | Stage #1: 4-(methanesulfonyl)acetophenone With sodium ethanolate at 0℃; for 0.75h; Stage #2: oxalic acid diethyl ester Reflux; | 21 4-methylsulfonylacetophenone (leq) was added at 00C to a solution of EtONa (prepared in situ with Na (1.3eq) and ethanol). The mixture was stirred 45min then diethyl oxalate was added dropwise. The mixture was refluxed overnight then concentrated to give the crude compound, which was diluted in ethyl acetate and was washed with HCl IN then water and brine. The organic layers were combined, dried on anhydrous Na2SO4, filtered and concentrated in vacuum. The residue was purified by flash chromatography (silica gel) to give the titled compound in 53% yield. IH- NMR (DMSO-t4): δ (ppm) 1.31 (t, 4H); 4.32 (q, 2H); 7.15 (s, IH); 8.10 (d, 2H); 8.30 (d, IH); MS (ESI+): m/z = 299 [M+H]+ |
With potassium <i>tert</i>-butylate In toluene at 20℃; for 8h; | ||
With sodium ethanolate In ethanol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30%; 68% | General procedure: A round-bottom flask that was flame-dried and cooled under dry air or oxygen atmosphere was charged with alcohol 6 or 33 (0.5 mmol) and THF (2.5 mL). After stirring at 0 C for 5 min, NaH powder (1 mmol, 2 equiv) was added in one portion, and the mixture was allowed to warm to room temperature. The reaction was quenched by addition of saturated NH4Cl (2 mL) after the indicated time, extracted with EtOAc (10 mL×2), and washed by brine (15 mL). The combined organic phase was dried over MgSO4, the solvent was removed under vacuum, and the residue was purified by flash chromatography on silica gel to give the desired ketone product 7 and 34. For isolations of acids 8 and 35/36: the combined aqueous phase was acidified with 2 M HCl, and then extracted with EtOAc (10 mL×2) and washed by brine (15 mL). The combined organic phase was dried over Na2SO4, the solvent was removed under vacuum to give acid product that can be further purified by flash chromatography on silica gel. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With acetic acid In ethanol at 70℃; | 2.2. General Synthesis of Hydrazone Derivatives. General procedure: An amountof acetic acid glacial was added to a mixture of acetophenoneand phenyl hydrazine derivatives in 20 ml ethanol (EtOH),and the reaction was reBuxed overnight at 70°C. Ethanol wasremoved under reduced pressure and the produced solidproduct was used without further puri7cation for pyrazolesynthesis. |
In ethanol; acetic acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With tetra-n-butylammonium tetrafluoroborate; hydrogen iodide In ethanol at 50℃; for 24h; Electrochemical reaction; Schlenk technique; Green chemistry; | |
90% | With indium trifluoromethanesulfonate; copper (I) iodide; oxygen In 1-methyl-pyrrolidin-2-one at 100℃; for 30h; Schlenk technique; | |
74% | With iodine In ethanol at 20℃; for 3h; Green chemistry; |
72% | Stage #1: 2-aminopyridine; 4-(methanesulfonyl)acetophenone With iodine; 3-butyl-1-methyl-1H-imidazol-3-ium hexafluorophosphate at 30 - 35℃; for 3h; Sonication; Stage #2: With potassium carbonate In water monomer at 40 - 45℃; for 0.333333h; Irradiation; | General procedure for the synthesisof imidazo[1,2-a]pyridines derivatives usingultrasonic irradiation General procedure: A mixture of acetophenone 1 (0.51 mmol), 2-aminopyridine2 (1.17 mmol), iodine (0.61 mmol), and 20 mol%[BMIM]PF6 (0.10 mmol) were added into a 5-cm3 driedflat-bottom capped-vial equipped with magnetic bar andirradiated at 30-45 C at a frequency of 40 kHz for 1-3 h.The reaction temperature of ultrasonic bath was controlledmanually by addition or removal of small amounts water.Then, the excess aqueous K2CO3 (35%) was subsequentlyadded and further irradiated at the same frequency at40-45 C for 20 min to accomplish the cyclization. Aftercompletion, the mixture was diluted with CHCl3 and neutralizedusing 3.5 M HCl. The organic layer was separatedand the aqueous layer was extracted with CHCl3. Thecombined organic layer was dried with Na2SO4 and concentratedunder reduced pressure. The crude product wasfurther purified by column chromatography using ethylacetate/hexane (1:9-2:8) to give the desired product. |
68% | With N-iodo-succinimide In water monomer at 80℃; for 6h; Green chemistry; | 4.3 Typical procedure for the synthesis of 2-arylimidazo [1,2-a]pyridines General procedure: A mixture of 2-aminopyridine 1a (94.11mg, 1mmol) and acetophenone 2a (120.15mg, 1mmol, 1 equiv.) in aqueous medium was stirred and heated at 80°C for 6h, after addition of NIS (224.98mg, 1mmol, 1 equiv.). After completion of the reaction (TLC), the mixture was cooled to room temperature and diluted with Et2O (10mL) and transferred into a separatory funnel. The organic layer was collected and further extracted with Et2O (2×10mL). The combined organic extract were dried (anh Na2SO4), filtered, then filtrate concentrated under rotary vacuum evaporation, and the residue was charged on to chromatography (100-200 mesh silica gel) column and eluted with EtOAc-hexane to afford pure 3a (192.36mg, 90%). All the remaining reactions were performed following this general procedure. |
68% | With N-iodo-succinimide In water monomer at 80℃; for 6h; Green chemistry; | 4.3 Typical procedure for the synthesis of 2-arylimidazo [1,2-a]pyridines General procedure: A mixture of 2-aminopyridine 1a (94.11mg, 1mmol) and acetophenone 2a (120.15mg, 1mmol, 1 equiv.) in aqueous medium was stirred and heated at 80°C for 6h, after addition of NIS (224.98mg, 1mmol, 1 equiv.). After completion of the reaction (TLC), the mixture was cooled to room temperature and diluted with Et2O (10mL) and transferred into a separatory funnel. The organic layer was collected and further extracted with Et2O (2×10mL). The combined organic extract were dried (anh Na2SO4), filtered, then filtrate concentrated under rotary vacuum evaporation, and the residue was charged on to chromatography (100-200 mesh silica gel) column and eluted with EtOAc-hexane to afford pure 3a (192.36mg, 90%). All the remaining reactions were performed following this general procedure. |
66% | With 1,10-Phenanthroline; Cu(OAc)2*H2O; zinc(II) iodide In 1,2-dichloro-benzene at 120℃; for 24h; | |
65% | With iron(III) trichloride hexahydrate; iodine; oxygen In chlorobenzene at 110℃; for 20h; Green chemistry; | |
64% | With copper (I) iodide; boron trifluoride diethyl ether complex; oxygen In N,N-dimethyl-formamide at 60℃; for 28h; | |
61% | With copper (I) iodide In 1,4-dioxane at 100℃; for 14h; | |
56% | In ethanol at 70℃; for 24h; | |
With copper (I) iodide; boron trifluoride diethyl ether complex In N,N-dimethyl-formamide at 60℃; for 24h; | Typical Procedure for the Synthesis of 2- Phenylimidazo[1,2-a]pyridine (3a) General procedure: 470 mg (5.0 mmol) of 2-aminopyridine 1a, 1200 mg (10 mmol) of acetophenone 2a, CuI 5 mol% (47 mg; 0.25 mmol), BF3·Et2O (45-50% purity); 10 mol%, 0.5 mmol) and DMF (2 mL) were placed in a 25-mL double-necked round-bottomed flask. The mixture was heated in an oil bath at 60 oC for 24 h under an oxygen atmosphere (balloon). After completion of the reaction, it was allowed to attain to room temperature and then the mixture was poured into 20 mL of sodium carbonate solution. The product was extracted with DCM (50 mL 3) and dried with anhydrous Na2SO4. Removal of the solvent under reduced pressure left a residue that was purified through column chromatography using silica gel (30% EtOAc/hexane) to afford 3a; yield: 0.799 g (82%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With indium(III) triflate; copper(l) iodide; oxygen In 1-methyl-pyrrolidin-2-one at 120℃; for 48h; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | In toluene for 3h; Reflux; | (E)-3-(Dimethylamino)-1-(4-(methylsulfonyl)phenyl)but-2-en-1-one (2d) 1-(4-(Methylsulfonyl)phenyl)ethanone (1d) (1.98 g, 10 mmol) was dissolved in dry PhMe (20mL) and DMADMA (2.19 mL, 15 mmol) was added to reaction mixture. Reaction mixture wasrefluxed for 3 h. Upon cooling the product precipitated from reaction mixture and was filtered of.Recrystallization from EtOAc. Yield: 1.69 g (63 %), yellow solid, mp 168.1-170.0 °C. 1H NMR(CDCl3, 300 MHz): δ 2.67 (3H, s, CH3); 3.12 (3H, s, CH3); 3.11 (6H, s, NMe2); 5.60 (1H, s,CH); 7.92-8.00 (4H, m, Ph). 13C NMR (CDCl3, 75.5 MHz): δ 16.7, 40.4, 44.5, 92.3, 127.2,128.1, 141.3, 148.2, 165.4, 185.8. (C13H17NO3S calculated: C, 58.40; H, 6.41; N, 5.24. found C,58.41; H, 6.58; N, 5.20); EI-HRMS: m/z = 268.1003 (MH+); C13H18NO3S calculated: m/z =268.1007 (MH+); νmax (KBr) 3011, 2997, 2917, 1608, 1538, 1477, 1434, 1385, 1353, 1306, 1290,1223, 1179, 1153, 1082, 1026, 973, 918, 863, 851 cm-1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydroxylamine hydrochloride; sodium acetate In methanol at 60℃; for 2h; | ||
With hydroxylamine hydrochloride; sodium acetate In methanol; water at 120℃; for 2h; | ||
With hydroxylamine hydrochloride; sodium acetate In ethanol; water at 100℃; for 6h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With sodium hydroxide In ethanol; water at 20℃; for 10h; | 3.2.1. 3-(5-Substituted-1H-indol-3-yl)/(1-methyl-1H-indol-3-yl)-1-(4-(substituted)phenyl)prop-2-en-1-ones (1-9) General procedure: A mixture of 4'-substituted acetophenone (0.05 mol), 5-substituted-1H-indole-3-carboxaldehydes/1-methylindole-3-carboxaldehyde (0.05 mol) and 10% aqueous sodium hydroxide (10 mL) in ethanol (30 mL) was stirred at room temperature for 10 h. The progress of the reaction was checked by TLC. Upon completation, the reaction mixture was poured into crushed ice. The precipitated solid was filtered, washed with water, and dried. The product was crystallized from ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With sodium hydroxide; In ethanol; water; at 20℃; for 10h; | General procedure: A mixture of 4'-substituted acetophenone (0.05 mol), 5-substituted-1H-indole-3-carboxaldehydes/1-methylindole-3-carboxaldehyde (0.05 mol) and 10% aqueous sodium hydroxide (10 mL) in ethanol (30 mL) was stirred at room temperature for 10 h. The progress of the reaction was checked by TLC. Upon completation, the reaction mixture was poured into crushed ice. The precipitated solid was filtered, washed with water, and dried. The product was crystallized from ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With sodium hydroxide In ethanol; water at 20℃; for 10h; | 3.2.1. 3-(5-Substituted-1H-indol-3-yl)/(1-methyl-1H-indol-3-yl)-1-(4-(substituted)phenyl)prop-2-en-1-ones (1-9) General procedure: A mixture of 4'-substituted acetophenone (0.05 mol), 5-substituted-1H-indole-3-carboxaldehydes/1-methylindole-3-carboxaldehyde (0.05 mol) and 10% aqueous sodium hydroxide (10 mL) in ethanol (30 mL) was stirred at room temperature for 10 h. The progress of the reaction was checked by TLC. Upon completation, the reaction mixture was poured into crushed ice. The precipitated solid was filtered, washed with water, and dried. The product was crystallized from ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With sodium hydroxide; In ethanol; water; at 20℃; for 10h; | General procedure: A mixture of 4'-substituted acetophenone (0.05 mol), 5-substituted-1H-indole-3-carboxaldehydes/<strong>[19012-03-4]1-methylindole-3-carboxaldehyde</strong> (0.05 mol) and 10% aqueous sodium hydroxide (10 mL) in ethanol (30 mL) was stirred at room temperature for 10 h. The progress of the reaction was checked by TLC. Upon completation, the reaction mixture was poured into crushed ice. The precipitated solid was filtered, washed with water, and dried. The product was crystallized from ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With 1-methyl-pyrrolidin-2-one; oxygen; copper dichloride In <i>tert</i>-butyl alcohol at 80℃; for 36h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With iodine; oxygen In 1,2-dichloro-benzene at 100℃; for 20h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With pyridine; oxygen; copper(I) triflate; trifluoroacetic acid In toluene at 130℃; for 28h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With copper(II) bis(trifluoromethanesulfonate); toluene-4-sulfonic acid In toluene at 100℃; for 36h; Schlenk technique; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide In ethanol; water at 20℃; for 10h; | 3.2.1. 3-(4-Substituted phenyl)-1-[4-(methylsulfonyl)phenyl]-2-propen-1-ones 1a-c General procedure: A mixture of 4'-(methylsulfonyl)acetophenone (0.05 mol), aromatic aldehyde (0.05 mol) and 10% aqueous sodium hydroxide (10 mL) in ethanol (30 mL) was stirred at room temperature for 10 h. The progress of the reaction was checked by TLC. Upon completion, the reaction mixture was poured into crushed ice. The precipitated solid was filtered, washed with water, and dried. The product was crystallized from ethanol [18]. | |
Stage #1: 4-(methanesulfonyl)acetophenone With sodium hydroxide In ethanol at 20℃; for 0.5h; Stage #2: 4-bromo-benzaldehyde In ethanol for 4h; | 3.2.1. General Procedure for Synthesis of Chalcones 3 and7 General procedure: Chalcones were synthesized via clasien-schmidt condensationof substituted benzaldehyde and acetophenones. For 3:4-substituted-acetophenone 2 (5 mmol) and for 7: 1-(4-(methylsulfonyl) phenyl)ethanone 5 (5 mmol), was dissolvedin 20 ml ethanol. NaOH pellet (10 mmol) was added to thissolution and stirred for 30 min at room temperature. Afterthat for 3: 4-(methylsulfonyl)benzaldehyde 1 (5 mmol) andfor 7: 4-substituted-benzaldehyde 6 (5 mmol) was added tothis solution and the stirring continued for 4 h. After completionof reaction, the solvent was evaporated and residuewas extracted with ethyl acetate and water. The purity ofcompounds was monitored by TLC using different solvents with different polarity. The organic layer was separated andevaporated under vacuum on a rotary evaporator and crystallizedby EtOH. No significant impurity was observed. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With tris(pentafluorophenyl)borate; hydrogen In toluene at 60℃; for 12h; Molecular sieve; | |
87% | With methanol; sodium tetrahydroborate In tetrahydrofuran at 0℃; for 2h; | A A. 1-(4-(Methylsulfonyl)phenyl)ethanol. To a 1000-mL 3-necked round-bottom flask was placed a solution of 1-(4-(methylsulfonyl)phenyl)ethanone (25 g,126.26 mmol) in a mixture of THF (100 mL) and MeOH (200 mL) then the solution was cooled to 0°C and NaBH4 (4.80 g,126.26 mmol) was added. The reaction was allowed to warm to rt and stirredfor 2 h,then quenched by the addition of water and extracted with EtOAc. The organic extracts were combined,washed with brine,dried over anhydrous Na2SO4,and concentrated under reduced pressure affording 22 g (87%) of the title compound as white solid. Mass Spectrum (LCMS,ESI pos): Calcd. for C9H13O3S: 201.1 (M+H); Found: 201.1. |
80% | With water; 1,8-diazabicyclo[5.4.0]undec-7-ene; bis(pinacol)diborane at 60℃; for 10h; Sealed tube; chemoselective reaction; |
77% | With chloro(1,5-cyclooctadiene)rhodium(I) dimer; potassium trifluoroacetate; diphenyl(methyl)phosphine; bis(pinacol)diborane; 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane In tetrahydrofuran; cyclohexane at 20℃; for 24h; regioselective reaction; | |
68% | With sodium tetrahydroborate In methanol at 0 - 25℃; | |
With methanol; sodium tetrahydroborate at 0 - 20℃; Inert atmosphere; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); water In acetonitrile at 80℃; for 8h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With sodium hydroxide In ethanol; water at 0 - 20℃; diastereoselective reaction; | (E)-3-(2,3-dimethoxyphenyl)-1-(4-(methylsulfonyl)phenyl)prop-2-en-1-one (3) General procedure: Chalcones were prepared utilizing Claisen-Schmidt condensation. To a stirred solution of the substituted acetophenone (1mmol) and the substituted benzaldehyde (1mmol) in ethanol at 0°C, sodium hydroxide solution (0.5ml, 50%) was added dropwise. The solution was then stirred at room temperature overnight. The formed precipitate was filtered and washed with cold water and recrystallized from ethanol, to afford chalcones 1-10. Pale yellow solid, yield=67%, m.p.=171-175°C, 1H NMR (400MHz, DMSO-d6) δ 8.35 (d, J=8.3Hz, 2H, H3 and H5), 8.11 (d, J=8.3Hz, 2H, H2 and H6), 8.04 (d, J=15.8Hz, 1H, β-Olefinic), 7.91 (d, J=15.8Hz, 1H, α-Olefinic), 7.64 (dd, J=6.4, 2.8Hz, 1H, H6′), 7.25-7.10 (m, 2H, H4′ and H5′), 3.85 (s, 3H, -OCH3), 3.81 (s, 3H, -OCH3), 3.31 (s, 3H, -SO2CH3). 13C NMR (101MHz, DMSO-d6) δ 188.76, 152.78, 148.48, 144.19, 141.39, 139.25, 129.36, 127.92, 127.42, 124.36, 122.69, 119.30, 115.45, 61.07, 55.86, 43.21. Anal. calcd. for C18H18O5S: C, 62.41; H, 5.24; S, 9.26. Found: C, 62.31; H, 5.27; S, 10.03. EI-MS (m/z): calculated 346.1, observed 346.1 (M) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With sodium hydroxide; In ethanol; water; at 0 - 20℃; | General procedure: Chalcones were prepared utilizing Claisen-Schmidt condensation. To a stirred solution of the substituted acetophenone (1mmol) and the substituted benzaldehyde (1mmol) in ethanol at 0C, sodium hydroxide solution (0.5ml, 50%) was added dropwise. The solution was then stirred at room temperature overnight. The formed precipitate was filtered and washed with cold water and recrystallized from ethanol, to afford chalcones 1-10. Yellow solid, yield=45%, m.p.=126-130C, 1H NMR (400MHz, DMSO-d6) delta 8.27 (d, J=7.4Hz, 2H, H3 and H5), 8.13 (d, J=7.3Hz, 2H, H2 and H6), 7.85 (d, J=15.6Hz, 1H, beta-Olefinic), 7.73 (d, J=15.6Hz, 1H, alpha-Olefinic), 7.37 (d, J=7.4Hz, 1H, H6?), 7.03 (d, J=7.0Hz, 1H, H4?), 6.94 (d, J=7.4Hz, 1H, H5?), 6.20 (s, 2H, -O-CH2-O-), 3.36 (s, 3H, -SO2-CH3). 13C NMR (101MHz, DMSO-d6) delta 188.85, 147.72, 146.93, 144.17, 141.32, 138.94, 129.22, 127.52, 123.49, 122.18, 122.03, 116.85, 110.50, 101.82, 59.76, 43.24, 20.75, 14.08. Anal. calcd. for C17H14O5S: C, 61.81; H, 4.27; S, 9.70. Found: C, 61.67; H, 4.25; S, 8.87. EI-MS (m/z): calculated 330.1, observed 330.1 (M) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With iodine In dimethyl sulfoxide at 110℃; for 24h; Schlenk technique; | Typical procedure for the synthesis of 3-acylbenzothiadiazine1,1-dioxides General procedure: A mixture of acetophenone (0.040 mL,0.33 mmol), I2 (0.057 g, 0.225 mmol) and 2-aminobenzenesulfonamide(0.051 g, 0.3 mmol) in DMSO (2 mL) was stirredat 110 °C under air atmosphere in a sealed 50 mL Schlenk tubefor 24 h. After the reaction was finished, the reaction mixturewas cooled to room temperature. The resulting mixture wastaken up by dichloromethane (60 mL) and washed with saturatedNa2S2O3 solution until the brown color disappeared. Theorganic phase was dried over Na2SO4 (anhydrous), concentratedin vacuum, and the resulting residue was purified bycolumn chromatography on silica gel with EtOAc/petroleum(1:4) to afford the product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With hydrogen iodide; boric acid In water; dimethyl sulfoxide at 115℃; for 6h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With toluene-4-sulfonic acid In methanol at 60℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With ammonium iodide In toluene at 150 - 160℃; for 30h; Inert atmosphere; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With dipotassium peroxodisulfate In methanol at 80℃; for 20h; | 8 Example 8: Synthesis of 1- (4- (methylsulfonyl) phenyl) ethanone O-methylOxime (3a) p-(methylsulfonyl)acetophenone (0.75 mmol, 152 mg), N-methoxybenzamide (0.5 mmol, 78.2 mg), potassium persulfate (1.0 mmol, 270.3 mg), 2 mL of anhydrous methanol were added to the reaction vessel,seal,The reaction was stirred at 80 ° C for 20 hours.Cooled to room temperature,After removal of the solvent under reduced pressure,Ethyl acetate = 5: 1) to give 1- (4- (methylsulfonyl) phenyl) ethanone O-methyl (5: 1) by column chromatography (eluent petroleum ether /Oxime (3a) 86.3 mg,Yield 76%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With iodine In dimethyl sulfoxide at 110℃; for 0.5h; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With nickel(II) tetrafluoroborate hexahydrate; ammonia; hydrogen; bis(2-diphenylphosphinoethyl)phenylphosphine In 2,2,2-trifluoroethanol at 120℃; for 24h; chemoselective reaction; | |
82% | With ammonia; hydrogen In tetrahydrofuran at 120℃; for 20h; | |
With ammonium hydroxide; hydrogen at 140℃; for 20h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | Stage #1: 4-(methanesulfonyl)acetophenone With 2,4,6-trimethyl-pyridine In toluene at 0℃; for 0.0833333h; Inert atmosphere; Stage #2: trifluoromethylsulfonic anhydride In toluene at 20 - 50℃; Inert atmosphere; | |
With 2,6-di-tert-butyl-4-methylpyridine In dichloromethane at 0 - 20℃; for 16h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With water at 110℃; for 12h; Sealed tube; Green chemistry; | A typical procedure for the synthesis of aryl methyl sulfones General procedure: Sodium benzenesulfinate (0.5 mmol), 2-(tert-butylperoxy)-2-methylpropane (1 mmol), and H2O (2.5 mL) were added into a 10 mL sealed tube successively. Then, the reaction was carried out at 110 C under magnetic stirring for 12 h. After the reaction was finished, the reaction mixture was extracted with ethyl acetate for three times (5 mL × 3). The obtained organic layer was dried with anhydrous MgSO4. The solvent was removed under vacuum, and the obtained crude product was purified by silica gel column chromatography with petroleum ether/ethyl acetate (10:1) as eluent to afford the desired pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With potassium phosphate; Fe(1,2-bis(dimethylphosphino)ethane)2Cl2; cesium fluoride In tetrahydrofuran at 20℃; for 24h; Glovebox; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With selenium; iodine(I) bromide In 1-methyl-pyrrolidin-2-one at 130℃; for 6h; Sealed tube; | |
With selenium; iodine trichloride In N,N-dimethyl-formamide at 130℃; for 20h; | 12 General procedure: tep 1: Add hydrazine compounds (see Table 1 for specific substances), ketone compounds (see Table 1 for specific substances) and selenium powder to the reaction vessel, and add the iodine-containing compound (see Table 1 for specific substances) to the reaction vessel. It is also possible to separately supply the container with iodine compounds (see Table 1 for specific substances) and organic solvents (see Table 1 for specific substances);Step 2: uniformly heating the reaction vessel (such as heating in an oil bath) to the temperature described in Table 1, and reacting the terpenoid, the ketone compound and the selenium powder in a solvent, and continuing the time described in Table 1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 4-(methanesulfonyl)acetophenone With sodium hydroxide In ethanol at 20℃; for 0.5h; Stage #2: 4-nitrobenzaldehdye In ethanol for 4h; | 3.2.1. General Procedure for Synthesis of Chalcones 3 and7 General procedure: Chalcones were synthesized via clasien-schmidt condensationof substituted benzaldehyde and acetophenones. For 3:4-substituted-acetophenone 2 (5 mmol) and for 7: 1-(4-(methylsulfonyl) phenyl)ethanone 5 (5 mmol), was dissolvedin 20 ml ethanol. NaOH pellet (10 mmol) was added to thissolution and stirred for 30 min at room temperature. Afterthat for 3: 4-(methylsulfonyl)benzaldehyde 1 (5 mmol) andfor 7: 4-substituted-benzaldehyde 6 (5 mmol) was added tothis solution and the stirring continued for 4 h. After completionof reaction, the solvent was evaporated and residuewas extracted with ethyl acetate and water. The purity ofcompounds was monitored by TLC using different solvents with different polarity. The organic layer was separated andevaporated under vacuum on a rotary evaporator and crystallizedby EtOH. No significant impurity was observed. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With sodium monohydrogensulphide hydrate; iodine In dimethyl sulfoxide at 20 - 100℃; for 7h; Sealed tube; | |
76% | Stage #1: 4-(methanesulfonyl)acetophenone With iodine In dimethyl sulfoxide at 100℃; for 1h; Stage #2: anthranilic acid nitrile With sodium hydrosulfide monohydrate In dimethyl sulfoxide at 100℃; for 7h; | 2 Example 2: Synthesis of (3-amino-1hydro-indol-2-yl)(4-(methylsulfonyl)phenyl)methanone: The specific steps were as follows: 4-methylsulfonylacetophenone (0.5 mmol), iodine (0.8 mmol) and 2 mL of DMSO were added to a 38 mL pressure-resistant tube.After the first reaction was carried out at 100 ° C for 60 min (4-methylsulfonylacetophenone completely disappeared),2-Aminobenzonitrile (0.5 mmol) was added to the reaction solution, and NaHS·H 2 O (2.5 mmol) was subjected to a second reaction at 100 ° C. After 7 hours, the reaction mixture was extracted with ethyl acetate.The organic layer was washed with saturated sodium thiosulfate and saturated brine, respectively.After drying over anhydrous sodium sulfate, the solvent is evaporated under reduced pressure to give a crude product.The crude product is purified by column chromatography using a mixture of petroleum ether and ethyl acetate to give a yellow solid.The total yield was 76%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With sodium monohydrogensulphide hydrate; iodine In dimethyl sulfoxide at 20 - 100℃; for 7h; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With selenium; oxygen; iodine(I) bromide In 1-methyl-pyrrolidin-2-one at 140℃; Sealed tube; | |
33% | With selenium; iodine trichloride In 1-methyl-pyrrolidin-2-one at 130℃; for 20h; | 14 Example 1-51 General procedure: Step 1: Add 2-aryl sulfonium compounds (see Table 1 for specific substances), aromatic ketone compounds (see Table 1 for specific substances) and selenium powder to the reaction vessel to contain iodine compounds (see Table 1 for specific substances). The solution may also be added to the reaction vessel to contain iodine compound (see Table 1 for specific substances) and organic solvent (see Table 1 for specific substances);Step 2: uniformly heat the reaction vessel (such as heating in an oil bath) to the temperature described in Table 1, and react the 2-aryl sulfonium compound, the aromatic ketone compound and the selenium powder in a solvent, and continue in Table 1. Said time; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With iodine; dimethyl sulfoxide; triphenylphosphine at 100℃; for 12h; | Typical Procedure for the Synthesis of 3-Sulfenylimidazo[1,2-a]pyridines General procedure: PPh3 (157.4 mg, 0.6 mmol) and I2 (38.1 mg, 0.15 mmol) were added to a solution of substrate 1 (0.3mmol), 2 (0.42mmol) and 3 (0.6 mmol) in DMSO (1 mL). The mixture was stirred at 100 °C under air for12 h. After the completion of the reaction (monitored by TLC), the reaction mixture was cooled to ambienttemperature, quenched by water and extracted with ethyl acetate (3 x 15 mL). The extract was washed with10% Na2S2O3 solution (w/w) (2 x 15 mL), dried over anhydrous Na2SO4 and the solvent was removed invacuo to provide a crude product, which was purified by column chromatography on silica gel withpetroleum ether/EtOAc as eluent to afford the product 4 or 5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With iodine(I) bromide In chlorobenzene at 130℃; for 4h; Sealed tube; | |
29% | With tertamethylammonium iodide; iodine(I) bromide In chlorobenzene; benzene at 150℃; for 8h; | 19 Embodiment 1 - 55 General procedure: Step 1: the 2 - aryl-indoles (specific material shown in table 1) and aromatic alkyne apperception compound or aromatic ketone compound (specific material see table 1) added in a reaction vessel, the iodine-containing compound (specific material see table 1) of the solution can also be added in a reaction vessel to iodine-containing compound in the container respectively (specific material shown in table 1) and organic solvent (specific material see table 1);Step 2: uniform heating of the reaction vessel (such as the oil bath is heated) to table 1 in the temperature, 2 - aryl indole compounds and aromatic alkyne apperception compound or aromatic ketone compound in the solvent in the reaction, and [...] 1 in the time; it should be noted that the reaction does not need to participate in the reaction atmosphere environment, therefore atmosphere can be selected air or inert gas, such as nitrogen. As long as the strong oxidation atmosphere can be reaction.Step 3: purification step.Table 1: embodiment 1 - 55 in 2 - aryl indole compounds with aromatic alkyne apperception compound or aromatic ketone compounds, iodine-containing compounds, organic solvent, (2 - aryl indole compounds, aromatic alkyne apperception compound or aromatic ketone compounds and iodine-containing compound) molar ratio, the reaction temperature and the reaction time. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With sodium nitrite In water; acetonitrile at 40℃; for 4.33333h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With bromopentacarbonylmanganese(I); dimethyl zinc(II); copper(II) bis(trifluoromethanesulfonate) In 1,2-dichloro-ethane; toluene at 80℃; for 17h; Inert atmosphere; Sealed tube; Schlenk technique; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With sodium hydroxide; In methanol; water; at 20℃; | General procedure: Chalcones analogs were synthesized by Claisen-Schmidt condensation reaction using appropriate equimolar amounts of substituted acetophenones and benzaldehydes in MeOH. NaOH was dissolved in the least amount of water and added dropwise (3mmol) (Scheme 1). Reactions were stirred overnight. All reactions were monitored by TLC using appropriate solvent or mixture of solvents. When the reaction was complete, the obtained precipitate was filtered, washed with cold methanol and dried under vacuum. The crude products were crystallized from different solvent systems based on their solubility or purified by column chromatography to give pure crystalline compounds. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With sodium hydroxide In methanol; water at 20℃; | General procedure: Chalcones analogs were synthesized by Claisen-Schmidt condensation reaction using appropriate equimolar amounts of substituted acetophenones and benzaldehydes in MeOH. NaOH was dissolved in the least amount of water and added dropwise (3mmol) (Scheme 1). Reactions were stirred overnight. All reactions were monitored by TLC using appropriate solvent or mixture of solvents. When the reaction was complete, the obtained precipitate was filtered, washed with cold methanol and dried under vacuum. The crude products were crystallized from different solvent systems based on their solubility or purified by column chromatography to give pure crystalline compounds. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With sodium hydroxide In methanol; water at 20℃; | General procedure: Chalcones analogs were synthesized by Claisen-Schmidt condensation reaction using appropriate equimolar amounts of substituted acetophenones and benzaldehydes in MeOH. NaOH was dissolved in the least amount of water and added dropwise (3mmol) (Scheme 1). Reactions were stirred overnight. All reactions were monitored by TLC using appropriate solvent or mixture of solvents. When the reaction was complete, the obtained precipitate was filtered, washed with cold methanol and dried under vacuum. The crude products were crystallized from different solvent systems based on their solubility or purified by column chromatography to give pure crystalline compounds. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With sodium hydroxide In methanol; water at 20℃; | General procedure: Chalcones analogs were synthesized by Claisen-Schmidt condensation reaction using appropriate equimolar amounts of substituted acetophenones and benzaldehydes in MeOH. NaOH was dissolved in the least amount of water and added dropwise (3mmol) (Scheme 1). Reactions were stirred overnight. All reactions were monitored by TLC using appropriate solvent or mixture of solvents. When the reaction was complete, the obtained precipitate was filtered, washed with cold methanol and dried under vacuum. The crude products were crystallized from different solvent systems based on their solubility or purified by column chromatography to give pure crystalline compounds. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With triethylamine; sodium iodide In acetonitrile at 20℃; Inert atmosphere; | |
Stage #1: 4-(methanesulfonyl)acetophenone With sodium iodide In acetonitrile at 25℃; for 0.0833333h; Schlenk technique; Inert atmosphere; Stage #2: chloro-trimethyl-silane With triethylamine at 40℃; Inert atmosphere; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56.4% | With iodine In dimethyl sulfoxide at 80℃; for 12h; | 13 Example 13 Add 0.793 g (4 mmol) of p-methanesulfonylacetophenone to the reaction tube containing the stirring magnet.Thiourea 0.152g (2mmol),0.051 g (0.4 mmol) of iodine and 4 ml of DMSO.The reaction tube was placed in an oil bath at 80 ° C. and the reaction was stirred for 12 h.After the reaction, the reaction solution was treated with a saturated NaHCO3 solution (20 mL).An additional 30 ml of water was added and extracted three times with 20 mL of ethyl acetate.The extract was washed with water and saturated NaCl solution, and dried over anhydrous Na2SO4.The solvent was removed under reduced pressure on a rotary evaporator, and the residue was separated by silica gel column chromatography.Eluted with petroleum ether / ethyl acetate (5: 1 by volume),To give 2-amino-4- (p-methylsulfonylphenyl) thiazole (0.287 g),The yield was 56.4%. |
56% | With iodine; dimethyl sulfoxide at 80℃; for 12h; Schlenk technique; | I2-catalyzed coupling reaction of ketones and thiourea: general procedure General procedure: A Schlenk tube (20 mL) was charged with ketone 1 (4 mmol),thiourea (2) (2 mmol), I2 (0.4 mmol) and DMSO (4 mL). Thetube was sealed with a rubber septum and the reaction mixturewas stirred at 80 °C for 12 h. After completion of thereaction, the mixture was cooled to room temperature. Ethylacetate (20 mL) and a saturated solution of NaHCO3 (20 mL)were added and the organic layer was separated. The aqueousphase was extracted with ethyl acetate (3 × 10 mL). Thecombined organic layer was washed with a saturated solutionof NaCl (20 mL) and then dried over anhydrous Na2SO4.After filtration, the solvent was removed under reduced pressure.The crude mixture was purified by chromatography onsilica gel to yield the desired products. |
51% | With iron(III) chloride hexahydrate; iodine at 110℃; for 24h; Sealed tube; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With acetic acid In ethanol at 70℃; | 2.2. General Synthesis of Hydrazone Derivatives. General procedure: An amountof acetic acid glacial was added to a mixture of acetophenoneand phenyl hydrazine derivatives in 20 ml ethanol (EtOH),and the reaction was reBuxed overnight at 70°C. Ethanol wasremoved under reduced pressure and the produced solidproduct was used without further puri7cation for pyrazolesynthesis. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With acetic acid In ethanol at 70℃; | 2.2. General Synthesis of Hydrazone Derivatives. General procedure: An amountof acetic acid glacial was added to a mixture of acetophenoneand phenyl hydrazine derivatives in 20 ml ethanol (EtOH),and the reaction was reBuxed overnight at 70°C. Ethanol wasremoved under reduced pressure and the produced solidproduct was used without further puri7cation for pyrazolesynthesis. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With acetic acid In ethanol at 70℃; | 2.2. General Synthesis of Hydrazone Derivatives. General procedure: An amountof acetic acid glacial was added to a mixture of acetophenoneand phenyl hydrazine derivatives in 20 ml ethanol (EtOH),and the reaction was reBuxed overnight at 70°C. Ethanol wasremoved under reduced pressure and the produced solidproduct was used without further puri7cation for pyrazolesynthesis. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 4-(methanesulfonyl)acetophenone With iron(III) chloride In ethyl acetate at 20℃; for 0.0166667h; Stage #2: With dimethylmonochlorosilane In ethyl acetate at 20℃; | General procedure for the deoxygenative chlorination of carbonyl compounds with HMe2SiCl General procedure: A 50 mL single-neck round-bottom flask was loaded with carbonyl compound (10.0 mmol), FeCl3 (0.0811 g, 0.5 mmol),and EtOAc (20 mL). The reaction mixture was stirred at room temperature for 1 min, and then HMe2SiCl (1.4193 g,15.0 mmol) was added. Subsequently, the reaction flask was equipped with a 90° glass joint with a balloon to protect the mixture from moisture. The reaction mixture was stirred vigorously at room temperature until the reaction was completed (as detected by thin-layer chromatography(TLC)). The solution was washed with saturated NaHCO3 solution (3 × 10 mL) to remove FeCl3. The organic layer was dried over anhydrous Na2SO4. The solvent was then removed under vacuum, and the mixture was purified via column chromatography to afford the product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With tin(II) trifluoromethanesulfonate In dichloromethane at 20℃; for 24h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | With silver trifluoromethanesulfonate; C54H58Cl4N4P2Pd2 In 1,4-dioxane at 80℃; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | Stage #1: 1-(4-methoxyphenyl)ethanone With sodium tungstate (VI) dihydrate; sodium peroxoborate tetrahydrate In acetone at 40℃; Stage #2: With sulfuric acid In water Reflux; | 1.5; 1.6 Step 5: Add 100g of p-acetylanisole and 400mL of acetone into the reaction flask and stir to dissolve.Furthermore, 8.0g of sodium tungstate dihydrate and 278.0g of sodium perborate tetrahydrate were added and heated to 40°C,The reaction mixture is obtained.Step 6: Dilute 80.0 g of concentrated sulfuric acid with 400 mL of water into 2N dilute sulfuric acid, slowly drop 2N dilute sulfuric acid into the reaction mixture, and exothermic the temperature to reflux. After the reaction is completed, the acetone is distilled out, the temperature is lowered to 0°C, filtered, and dried to obtain 119 g of 4'-(methylsulfonyl)acetophenone with a purity of 99%.The yield was 100%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With potassium hydroxide In N,N-dimethyl-formamide at 100℃; | General procedure for the synthesis of compound 7(a-o): General procedure: The synthesis was carried out in a single step via the classical multicomponent reaction (MCR). A mixture of 3-amino-[1,2,4]triazole (1.2 mmol), aldehyde (1 mmol) and substituted ketones (1 mmol) in 2 mL of dimethylformamide, were placed in a round- bottomed flask with potassium hydroxide (2 mmol) was added at room temperature. It was heated up to 95-100 °C for 3-5 h. Reaction progress was monitored by TLC. After the completion of the reaction, the mixture was poured into crushed ice and the reaction mixture was then extracted with ethyl acetate, washed with water and dried over sodium sulphate, filtered and finally, the solvent was evaporated on the rotary evaporator. The crude product was purified by column chromatography on silica, using a hexane- ethyl acetate (80:20) solvent to afford the product as a solid. The specific procedure for each of the compounds is mentioned in the experimental section. |
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P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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