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Oxindole is an aromatic heterocyclic organic compound which causes sedation, muscle weakness, hypotension, and coma when dosed in excess.
Synonyms: 2-Indolinone; NSC 274863; Indolin-2-one
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CAS No. : | 59-48-3 |
Formula : | C8H7NO |
M.W : | 133.15 |
SMILES Code : | O=C1NC2=C(C=CC=C2)C1 |
Synonyms : |
2-Indolinone; NSC 274863; Indolin-2-one
|
MDL No. : | MFCD00005711 |
InChI Key : | JYGFTBXVXVMTGB-UHFFFAOYSA-N |
Pubchem ID : | 321710 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
* 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 |
---|---|---|
85% | With piperidine In ethanol at 90℃; Inert atmosphere | General procedure: The appropriate aldehyde (1 equiv) was added to EtOH (3 mL/0.2 mmol) and the mixture was stirred until complete solution. Theoxindole (1 equiv) and piperidine (0.1 equiv) were added, and themixture was heated to 90°C for 3-7 h, and cooled. The resultingprecipitatewas filtered, washed with cold ethanol and dried to givethe pure compound. If necessary, additional recrystallization inethanol was applied to obtain the pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
25% | With piperidine In ethanol for 3 h; Reflux | General procedure: The preparation of compounds 3-25 was carried out by refluxing oxindole with different aromatic aldehydes in ethanol in the presence of a catalytic amount of piperidine were refluxed for 3 h. After cooling reaction mixture was concentrated at reduced pressure to obtain solid of 3-oxindole derivatives, then washed with 1:1 mixture of hexane-ethyl acetate (25 mL) and dried to afford titles compoundsin good yields (Table 1). Only in two cases (10 and21), both E and Z isomers were obtained, these isomers wereseparated by column chromatography using 1:9 ethyl acetate: hexane as eluent. The structures of synthetic compounds 3-25 were elucidated by 1H NMR and EI MS. Elemental analysis results were also found to be satisfactory. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
4 g | With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; | Stir the mixture of <strong>[35613-44-6]methyl 2-(2-aminophenyl)acetate</strong> (4.8 g, 29.1 mmol) and potassium carbonate (8.0 g, 58.2 mmol) in DMF (15 mL) at room temperature overnight. TLC (PE:EtOAc=2:l) shows the reaction is complete. Concentrate the reaction mixture under reduced pressure to give the crude product. Purify by chromatography (silica gel, EtOAc:PE=l:2) to afford the title compound (4.0 g, 95%). MS: (M+l): 134.2. |
4 g | With potassium carbonate; In N,N-dimethyl-formamide; at 25℃; | Stir the mixture of <strong>[35613-44-6]methyl 2-(2-aminophenyl)acetate</strong> (4.8 g, 29.1 mmol) and potassium carbonate (8.0 g, 58.2 mmol) in DMF (15 mL) at room temperature overnight. TLC (PE:EtOAc=2:1) shows the reaction is complete. Concentrate the reaction mixture under reduced pressure to give the crude product. Purify by chromatography (silica gel, EtOAc:PE=1:2) to afford the title compound (4.0 g, 95%). MS: (M+1): 134.2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
680.2 mg (62%) | In ethanol; | 3-[2-Chloro-4-methoxybenzylidenyl]-2-indolinone (SU5480). The reaction mixture of 487.9 mg (3.7 mmoles) of oxindole, 750 mg (4.3 mmoles) of <strong>[54439-75-7]2-<strong>[54439-75-7]chloro-4-methoxybenzaldehyde</strong></strong> and 4 drops of piperidine in 5 mL of ethanol was heated to 90° C. for 2 h and cooled to room temperature. The yellow precipitate was filtered, washed with cold ethanol, and dried at 40° C. in a vacuum oven overnight to give 680.2 mg (62percent) of the title compound. |
680.2 mg (62%) | In ethanol; | 3-[2-Chloro-4-methoxybenzylidenyl]-2-indolinone (SU5480). The reaction mixture of 487.9 mg (3.7 mmoles) of oxindole, 750 mg (4.3 mmoles) of <strong>[54439-75-7]2-<strong>[54439-75-7]chloro-4-methoxybenzaldehyde</strong></strong> and 4 drops of piperidine in 5 mL of ethanol was heated to 90° C. for 2 h and cooled to room temperature. The yellow precipitate was filtered, washed with cold ethanol, and dried at 40° C. in a vacuum oven overnight to give 680.2 mg (62percent) of the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With piperidine; In ethanol; at 80℃; for 2h; | 3- ( (5-bromo-2-methoxypyridin-3-yl)methylene) indolin-2-one EPO <DP n="53"/>[00119] To a solution of indolinone (130mg, 0.98mmol) in ethanol (5mL) was added 5-bromo-2-methoxypyridine-3- carbaldehyde (J. net. Chem, 1985, (22), 1583-1592) (200mg, 0.98mmol, leq) , followed by piperidine (0.194mL, 1.9mmol, 2eq) . The reaction mixture was heated at 8O0C for 2 hours and then allowed to cool to room temperature. The precipitate that formed was collected by filtration and washed with ethanol to give the title compound (180mg, 55%; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
INTERMEDIATE 18(2-Oxo-2'.3'.5'.6'-tetrahvdrospirorindole-3.4'-Pyran1-l(2H)-vnacetic acidStep A. 2'.3'.5'.6'-Tetrahvdrospirorindole-3.4'-pyran1-2?/f)-oneButyllithium (2.5 M in hexanes, 3.76 mL, 9.39 mmol) was added to a solution of oxindole (500 mg, 3.76 mmol) at -78 0C in THF (40 mL). After complete addition, NJIJt'.N'- tetramethylethane-l,2-diamine (1.48 mL, 9.76 mmol) was added, maintaining the internal temperature < -70 C. After 1 h at -78 C, 2-iodoethyl ether (4.90 g, 15.0 mmol) was added and the reaction warmed to ambient temperature. After 48 h the reaction was quenched with H2O (5 mL) and the mixture was partitioned between EtOAc (100 mL) and H2O (100 mL). The aqueous solution was extracted with EtOAc (3 chi 50 mL) and the combined organic layers were washed with brine (20 mL), dried over Na2SO4, filtered, and concentrated in vacuo. Purification by silica gel chromatography, eluting with a gradient Of CH2Cl2MeOH - 100:0 to 97:3, gave the title compound. MS: m/z = 204 (M + 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
16% | With pyrrolidine; In toluene; at 50℃;Reflux; | A solution of oxindole (16 mg, 0.12 mmol), pyrrolidine (10 μL, 0.12 mmol) and l-(lH-indazol-6-yl)ethanone (20 mg, 0.12 mmol) in toluene was refluxed in a Dean-Stark trap for 2 h. The solution was then stirred at 50 0C for 72 h. Two equivalents of pyrrolidine were added and the solution was heated to reflux for 48 h. The solution was concentrated and the red residue was purified by preparatory HPLC to give the title compound as an orange solid (5 mg, 16%). 1H NMR (400 MHz, CDCl3) δ 8.13 (s, IH), 7.78 (s, IH), 7.70 (d, IH, J = 8.5 Hz), 7.34 (d, IH, J = 8.5 Hz), 7.03 (t, IH, J = 7.6 Hz), 6.81 (d, IH, J = 7.7 Hz), 6.50 (t, IH, J = 7.6 Hz), 6.05 (d, IH, J = 7.7 Hz), 2.82 (s, 3H); MS ESI [M + H]+, calcd for [Ci7Hi3N3O +H]+ 276.1; found m/z 276.0. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Butyllithium (2.5 M in hexanes, 3.76 mL, 9.39 mmol) was added to a solution of oxindole (500 mg, 3.76 mmol) at -78 0C in TEtaF (40 mL). After complete addition, NJSfJSf1N- tetramethylethane-l,2-diamine (1.48 mL, 9.76 mmol) was added, maintaining the internal temperature < 70 0C. After 1 h at -78 0C, 2-iodoethyl ether (4.90 g, 15.0 mmol) was added and the reaction warmed to ambient temperature. After 48 h the reaction was quenched with H2O (5 mL) and the mixture was partitioned between EtOAc (100 mL) and H2O (100 mL). The aqueous solution was extracted with EtOAc (3 x 50 mL) and the combined organic layers were washed with brine (20 mL), dried over Na2SO4, filtered, and concentrated in vacuo. Purification by silica gel chromatography, eluting with a gradient of CH2Cl2MeOH- 100:0 to 97:3, gave the title compound. MS: m/z = 204 (M + 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dihydrogen peroxide; iron(II); In water; at 20℃;pH 2.0; | General procedure: For the Fenton degradation experiment, 10 mL of a Milli Q water sample acidified at pH 2 with 100 muL H2SO4 0.5 mol/L containing 200 ng of each studied anti-inflammatory drug (diclofenac sodium, ibuprofen and ketoprofen) was placed into a 50 mL brown glass bottle. Immediately, 500 muL of Fe2+solution (1 mg/mL Fe2+) and 200 muL of H2O2 (30percent) were added into the brown bottle which was kept under magnetic stirring and room temperature for different time intervals in order to perform the degradation process. Because the catalyst (Fe2+) and the oxidant (H2O2) are consumed very fast, these were refreshed at each 30 minutes in the same amounts as it was described previously. To study the Fenton oxidative process efficiency over the selected drugs, different experiments at 30, 60 and 120 minutes were performed. After each Fenton oxidative experiment, the degradation by-products of NAIDs were extracted with organic solvent and analyzed by GC×GC-qMS. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With piperidine; In ethanol;Reflux; | General procedure: To a mixture of oxindole (3a-f, 0.3mmol), 1-alkyl-1H benzo[d]imidazole-2-carbaldehydes (7a-e, 0.33mmol) in ethanol (2mL), was added catalytic amount of piperidine. The reaction mixture was stirred at reflux until complete consumption of the oxindole observed by TLC. After cooling, the precipitate was filtered, washed with cold ethanol, and dried in air to furnish pure (E)-benzo[d]imidazol-2-yl)methylene)indolin-2-ones 8a-z orange/yellow solids in moderate to good yields. Compounds 8c, 8f, 8i, 8l and 8o did not precipitated out from ethanol, were purified by column chromatography with silica gel (60-120) by using ethyl acetate:hexane (2:8 to 3:7). 4.1.1.1 (E)-3-((1-Methyl-1H-benzo[d]imidazol-2-yl)methylene)indolin-2-one (8a) Orange solid, Yield 87%; mp: 255-257 C; FT-IR: (cm-1): 3186, 3151, 3063, 1705, 1605, 1329, 781, 763; 1H NMR (500 MHz, DMSO-d6): δ 10.71 (brs, 1H, NH), 9.49 (d, J = 7.6 Hz, 1H, Ar-H), 7.84 (d, J = 7.9 Hz, 1H, Ar-H), 7.69 (d, J = 8.1 Hz, 1H, Ar-H), 7.58 (s, 1H, C=CH), 7.42-7.29 (m, 3H, Ar-H), 7.07 (t, J = 7.8 Hz, 1H, Ar-H), 6.90 (d, J = 7.8 Hz, 1H, Ar-H), 4.02 (s, 3H, CH3); 13C NMR (75 MHz, DMSO-d6): δ 168.4, 147.2, 143.1, 142.3, 135.1, 130.9, 130.2, 127.5, 123.6, 122.5, 120.9, 120.6, 119.2, 117.3, 110.3, 109.1, 29.8; HRMS (ESI): m/z calcd for C17H14N3O 276.1137, found 276.1125 [M+H]+; Purity: 98.5%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With hydrogenchloride; acetic acid; In water; at 120 - 128℃; | General procedure: A mixture of 2-bromoaniline or 3-bromoaniline (110 mmol, 18.9 g), chloral hydrate (118.8 mmol,19.6 g), anhydrous sodium sulfate (880 mmol, 125 g), and hydroxylamine hydrochloride (347.6mmol, 24.2 g) in water (700 mL) was heated under reflux for 25 min to form a yellow precipitate. 50mL of ethanol was added after that and left to boil for another 4 min before filtration. The resultedisonitrosoacetanilide was then heated with sulfuric acid (150 mL) at 70 C for about 10 min thenpoured into ice water to form an orange precipitate. When using 3-bromoaniline, an extra step ofseparation is required by solving the resulted mixture in 0.25 M NaOH (1 L), filtering it, then addingacetic acid (100 mL) to afford 4-bromoistain as a precipitate. 6-Bromoistin can be then obtained whenlowering the pH of the solution to 1 by hydrochloric acid 37%.All substituted bromo-isatins were methylated by stirring (22 mmol, 4.97 g) with sodiumhydride (2 mmol, 0.968 g) and dimethylsulfate (23.1 mmol, 2.19 mL) in dried DMF (50 mL) undernitrogen atmosphere. The resulting mixture was poured after 2 h in ice water (100 mL) to form anorange precipitate.The methylated bromo-isatins (2 mmol, 0.480 g) were treated after that with oxindole (2 mmol,0.226 g) in a 100:1 mixture of glacial acetic acid and hydrochloric acid 37% (12 mL) in reflux for about 3 h. Then, they were poured in ice water (50 mL) to afford 5-, 6- and 7-bromomeisoindigo. While 4'-, 5'-, 6'- and 7'-bromomeisoindigo were obtained by reacting unmethylated bromo-isatins(2 mmol, 0.452 g) with 1-methyloxindole (2 mmol, 0.294 g) in the same conditions. The resultedprecipitates were washed with water, ethanol (2 x 10 mL), and diethylether (2 10 mL) then dried. |
Tags: Oxindole | 2-Indolinone | Indolines | Amides | Organic Building Blocks | Heterocyclic Building Blocks | 59-48-3
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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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