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CAS No. : | 583-75-5 | MDL No. : | MFCD00007825 |
Formula : | C7H8BrN | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | PCHYYOCUCGCSBU-UHFFFAOYSA-N |
M.W : | 186.05 | Pubchem ID : | 11423 |
Synonyms : |
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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: |
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* 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 |
---|---|---|
With 2 wt% Pd/C; hydrogen; at 120℃; under 7500.75 Torr; | Examples 27 to 34 investigated the effect of carbon-supported large-particle palladium catalysts on the synthesis of halogenated aromatic amines by solvent-free hydrogenation of different halogenated aromatic nitro compounds. In a 500 ml reactor, 200 g of different halogenated aromatic nitro compounds were added, 2 g of a 2 wt% palladium catalyst containing a large particle size in Example 5, shutting down the reactor; first with nitrogen replacement reactor inside the air three times, and then replaced with hydrogen three times, And then heated to 120 C, and the hydrogen pressure rose to 1MPa, open stirring to 1000r/min; to maintain the reaction temperature and pressure until the end of the reaction; cooling cooling, remove the reactor liquid, filter separation The catalyst was used and the water in the filtrate was separated by phase separation to give the desired product Halogenated aromatic amine. The reaction product was analyzed by gas chromatography. The results are shown in Table 4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With dihydrogen peroxide; trifluoroacetic anhydride; In dichloromethane; at 0℃; for 1.58333h;Heating / reflux; | Example 37; 2-methoxy-N-(2-methyl-4-(1-(2-(methylamino)ethyl)piperidin-4-yl)phenyl)benzamide (199); Step 1 4-bromo-2-methyl-1 -nitrobenzene (193); [0383] To a mixture of H2O2 (3 95 ml, 64 5 mmol) in DCM (32 0 ml) cooled at O 0C was added TFAA (10 93 ml, 77 mmol) and the mixture was stirred for 5 minutes at that temperature then the ice bath was removed and a reflux condenser was installed and a solution of 4-bromo-2-methylaniline (3 g, 16 12 mmol) in DCM (6 4 ml) was added drop-wise over approx 30 minutes The reaction was heated at reflux for an additional hour then it it was cooled, washed with 30 mL of water then 30 mL of sat NaHCO3 and the organic layer was dried over MgSO4 and concentrated under vacuum The crude material was purified by flash to afford 193 (2 57 g, 1 1 9 mmol, 74%) 1H NMR (CDCI3) delta (ppm) 7 88 (d, J = 8 6 Hz, 1 H),7 53 (d, J = 2 2 Hz, 1 H), 7 49 (dd, J = 8 6, 2 2 Hz, 1 H), 2 60 (s, 3H) |
With sulfuric acid; dihydrogen peroxide; In hexane; water; acetic acid; | Step A: Preparation of 5-bromo-2-nitrotoluene A solution of 4-bromotoluidine (27.9 g, 150 mmoles) in glacial acetic acid (600 ml) is stirred while 30% hydrogen peroxide (180 ml) and concentrated sulfuric acid (12 ml) are added. The mixture is heated in an oil bath at 100. When the pot temperature reaches 65 the mixture darkens and there is a mild exotherm. The bath is removed and the temperature rises to 105. When the reaction subsides, the bath is replaced and reflux is maintained for two hours. The mixture is cooled and poured onto ice (1500 g). The product crystallizes slowly with scratching. Another liter of cold water is added and the product is filtered and washed. The damp solid is dissolved in hexane, filtered, dried and evaporated to a residue which crystallizes to give 14.3 g of 5-bromo-2-nitrotoluene, containing minor contaminants by tlc [silica gel-dichloromethane/hexane (3:7)] which were removed by column chromatography using the same solvent system. Final weight; 12.8 g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: Catalytic reaction was carried out in a 50 mL two necked round bottom flask, which charged with 0.05 g of catalyst, substrate (2 mmol) in acetic acid (5 mL) and KBr (2.2 mmol). 30% H2O2 (2.2 mmol) was then added drop wise to the reaction mixture. The content in the flask was stirred continuously at room temperature. After specified time of the reaction, the catalyst was filtered and the solid was washed with ether. The combined filtrates were washed with saturated sodium bicarbonate solution and then shaken with ether in a separating funnel. The organic extract was dried over anhydrous sodium sulfate. The products were analysed by Varian 3400 gas chromatograph equipped with a 30 m CP-SIL8CB capillary column and a Flame Ionization Detector. Identity of the products was also confirmed by using an Agilent GC-MS. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyrrolidine; In N,N-dimethyl-formamide; at 110℃; for 1.5h; | 4-Bromo-2-(2,2-dimethoxyethyl)-1-nitrobenzene (66): Compound 64 (500 mg, 2.315 mmol) (Olsen et al., U.S. Pat. No. 4,287,201) was dissolved in anhydrous dimethylformamide (10 mL) in a dry argon purged flask fitted with a magnetic stir bar and condenser. Dimethylformamide dimethylacetal (828 mg, 6.945 mmol) and pyrrolidine (165 mg, 2.315 mmol) are added to the flask and mixture heated 110 C. for 90 minutes. After cooling to room temperature, the reaction mixture was diluted with diethyl ether and H2O, transferred to a separatory funnel and the organic layer collected. The organic layer washed with H2O (twice) and the combined aqueous layers back extracted with diethyl ether (twice). The combined organic layers were dried over anhydrous sodium sulphate, filtered, concentrated to yield a dark red oil, 65, which is utilized without purification. The crude enamine is dissolved in anhydrous methanol, treated with chlorotrimethylsilane (3 equivalents) and refluxed for 20 hours. The reaction was concentrated under reduced pressure and the residue was partitioned between a saturated sodium bicarbonate solution and ethyl acetate. The mixture was transferred to a separatory funnel and the organic layer collected. The aqueous layer was further extracted with ethyl acetate and the combined organic layers were washed with brine, dried over sodium sulphate, filtered, concentrated and the residue purified via chromatography on silica gel (EtOAc:Hexanes, 1:9) to yield a pale brown solid, 66 (330 mg, 49.2%). 1H NMR (CDCl3) delta 3.20 (d, 2H, J=5.2 Hz), 3.35 (s, 6H), 4.55 (t, 1H, J=5.2 Hz), 7.51 (dd, 1H, J=8.5, 2.1 Hz), 7.58 (d, 1H, J=1.9 Hz), 7.78 (d, 1H, J=8.6 Hz); ESI-MS (m/z, %): 312/314 (M+Na+, 90%), 198/200 (100%); ESI-HRMS calculated for C10H12NO4NaBr (M+Na+), calculated: 311.9841; observed: 311.9826. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
B. (4-Bromo-2-methyl-phenyl)-( 1 -pyrimidin-2-yl-piperidin-4-yl)-amine : To the mixture of 4-bromo-2-methylaniline (285 mg, 1.5 mmol) and l-pyrimidin-2-yl-piperidin- 4-one (266 mg, 1.5 mmol) in MeOH/AcOH (10:1, 5 ml) was added BH3-Py in THF (8M, 188 mul). The mixture was stirred at rt for 2h. The reaction mixture was concentrated and to the residue was added HCl (10%, 10 ml). The resulting mixture was stirred at room temperature for 30 min., then with cooling, the mixture was adjusted to alkaline with solid Na2CO3 and water. The aqueous layer was extracted with EtOAc (5 x 30 ml). The EPO <DP n="19"/>EtOAc was dried (Na2SO4) and concentrated. The residue was subjected to ISCO to give the titled compound as a white solid (140 mg). HPLC: column, Luna Phenyl-Hexyl 5 mum 4.6x50 mm, 10-90% solvent B (acetonitrile) in solvent A (IO mM ammonium acetate aq) over 3 min., flow rate 3 ml/min, retention time, 2.71 min.; MS (MH+: 347 and 349). 1H NMR (400 MHz, chloroform- d), delta ppm 1.46 (ddd, J=24.30, 10.86, 4.04 Hz, 2H), 2.10 (s, 3 H), 2.17 (dd, J=13.14, 2.78 Hz, 2 H), 3.20 (ddd, J=14.00, 11.87, 2.78 Hz, 1 H), 3.40 (br. s., 1 H), 3.60 (br. s., 1 H), 4.68 (ddd, J=13.52, 3.41, 3.28 Hz, 2 H), 6.50 (t, J=4.67 Hz, 1 H), 6.57 (d, J=8.59 Hz, 1 H), 7.19 (s, 1 H), 7.23 (dd, J=8.59, 2.27 Hz, 1 H), 8.33 (d, J=4.80 Hz, 2 H).; B. (4-Bromo-2-methyl-phenyl)-( 1 -pyrimidin^-yl-piperidin^-yl)- amine : To the mixture of bromoaniline (285 mg, 1.5 mmol) and ketone (266 mg, 1.5 mmol) in MeOH/AcOH (10:1, 5 ml) was added BH3-Py in THF (8M, 188 mul). The mixture was stirred at rt for 2h. The reaction mixture was concentrated and to the residue was added HCl (10%, 10 ml). The resulting mixture was stirred at rt for 30 min., then with cooling, EPO <DP n="25"/>the mixture was adjusted to alkaline with solid Na2CO3 and water. The aq. layer was extracted with EtOAc (5x 30 ml). The EtOAc was dried (Na2SO4) and concentrated. The residue was subjected to ISCO to give the titled compound as a white solid (140 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene;Inert atmosphere; Reflux; | Toluene (9 mL), ethanol (6 mL) and water (3 mL) were added into the mixture of MO(0.95 g, 5 mniol) 4-hromo2chloroaniline, (3..isopropyiphenyi) horonic acid (0.82 g, 5mmoi) and potassium carbonate (1.73 g, 12.5 mmol), stirred with nitrogen replacementfor three times. Additional replacement with nitrogen was performed for three times after0.3 g of tetraphenyiphenyiphosphine palladium was added. Then the reaction was warmed up for refiux reaction overnight. The product was filtered and concentrated, then 2() mL of dichioromethane and 10 mL of water were added and stirred for 1() mm. The liquid was separated and washed with 10 mL of water twice, dried with anhydroussodium sulfate, filtered, concentrated and purified by column chromatography. 0.83 g of M15 was achieved, with yield of 73%. |
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