| 32% |
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In tetrachloromethane; for 16h;Reflux; |
186 g (1.2 mol) of <strong>[455-88-9]2-fluoro-5-nitrotoluene</strong> are dissolved in 1.2 l of tetrachloromethane and admixed with 214 g (1.20 mol) of N-bromosuccinimide. 19.7 g (120 mmol) of azodiisobutyronitrile are added and the mixture is heated under reflux. After 16 h, the mixture is allowed to cool, filtered and concentrated to dryness under reduced pressure. The residue is dissolved in 300 ml of dichloromethane and admixed with 300 g of Seesand. Then the mixture is concentrated to dryness under reduced pressure again, and the residue is applied to a 1 kg silica gel column. It is chromatographed with a 20:1 mixture of cyclohexane and ethyl acetate, and the product fractions are concentrated to dryness under reduced pressure. The residue is crystallized with cyclohexane and dried under reduced pressure. This affords 92 g (32percent of theory) of the desired product. 1H NMR (400 MHz, DMSO-d6, delta/ppm): delta=8.57-8.52 (m, 1H), 8.33-8.27 (m, 1H), 7.56 (t, 1H), 4.62 (s, 2H). GC-MS (Method 9): Rt=7.79 min MS (ESIpos): m/z=154 (M-Br)+ |
| 28% |
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In chloroform; for 18h;Reflux; |
905 g (5.83 mol) of <strong>[455-88-9]2-fluoro-5-nitrotoluene</strong> and 1038 g (5.83 mol) of N-bromosuccinimide were introduced as initial charge in 5.83 l of chloroform, 47.8 g (0.29 mol) of 2,2?-azobis[isobutyronitrile] were added and the reaction mixture was heated at reflux for 18 h. After cooling to RT, the liquid was filtered off from the solid by suction and the filtrate was divided into three portions. These were absorbed in each case on 1.5 kg of silica gel (0.06-0.2) and chromatographically purified on in each case 10 kg of silica gel with 160 l of ethyl acetate:petroleum ether (2.5:97.5). The product fractions were combined and evaporated to dryness on a rotary evaporator, and the residue was extracted by stirring with petroleum ether for 10 min. The solid was filtered off with suction, after-washed with petroleum ether and dried in vacuo. 385 g (28percent) were obtained. [0120] HPLC (method 3): Rt=3.95 min. [0121] 1H NMR (400 MHz, DMSO-d6): delta [ppm]=4.82 (s, 2H), 7.57 (t, 1H), 8.30 (ddd, 1H), 8.55 (dd, 1H). [0122] MS (EI+): [M-Br]+ 154. |
| 18% |
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile);Reflux; |
A mixture of <strong>[455-88-9]1-fluoro-2-methyl-4-nitrobenzene</strong> (2.5 g, 16.12 mmol) NBS (5.02 g, 28.2 mmol) and AIBN (265 mg, 1.612 mmol) in trifluorotoluene (45 mL) was heated to reflux overnight. The mixture was cooled to RT, filtered to remove solids and the filtrate concentrated to dryness. The residue was dissolved in Et2O, washed with water, then brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (EtOAc/Hex) to afford 2-(bromomethyl)-1-fluoro-4-nitrobenzene (698 mg, 18percent yield). 1H NMR (400 MHz, DMSO-d6): delta 8.53 (dd, J=6.4, 3.0 Hz, 1H), 8.28 (ddd, J=9.1, 4.4, 3.0 Hz, 1H), 7.55 (t, J=9.2 Hz, 1H), 4.80 (s, 2H). |
| 18% |
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile);Reflux; |
Example 94: A mixture of <strong>[455-88-9]1-fluoro-2-methyl-4-nitrobenzene</strong> (2.5 g, 16.12 mmol)NBS (5.02 g, 28.2 mmol) and AIBN (265 mg, 1.612 mmol) in trifluorotoluene (45 mL) washeated to reflux overnight. The mixture was cooled toRT, filtered to remove solids and thefiltrate concentrated to dryness. The residue was dissolved in Et20, washed with water, thenbrine, dried over Na2S04, concentrated to dryness and purified via silica gel chromatography(EtOAc/Hex) to afford 2-(bromomethyl)-1-fluoro-4-nitrobenzene (698 mg, 18percent yield). 1HNMR (400 MHz, DMSO-d6): 8 8.53 (dd, J = 6.4, 3.0 Hz, 1 H), 8.28 (ddd, J = 9.1, 4.4, 3.0 Hz,1 H), 7.55 (t, J = 9.2 Hz, 1 H), 4.80 (s, 2 H). |
|
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); 2,3,4-trifluorotoluene;Reflux; |
Example D3: A mixture of <strong>[455-88-9]1-fluoro-2-methyl-4-nitrobenzene</strong> (2.5 g, 16.12mmol) and NBS (3.16 g, 17.73 mmol) in trifluorotoluene (45 mL) was treated with AIBN (66mg, 0.403 mmol) and heated at 80°C overnight. The mixture was cooled to RT, the solidsremoved via filtration and the filtrate concentrated to dryness. The residue was dissolved inEtOAc, washed with water, then brine, dried over Na2S04, concentrated to dryness andpurified via silica gel chromatography (EtOAc/Hex) to afford 2-(bromomethyl)-1-fluoro-4-nitrobenzene (1.915 g, 50percent yield). 1H NMR (400 MHz, DMSO-d6): 8 8.53-8.52 (m, 1 H),8.28 (ddd, J = 9.1, 4.4, 3.0 Hz, 1 H), 7.55 (t, J = 9.2 Hz, 1 H), 4.80 (s, 2 H). |
|
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In tetrachloromethane; for 48h;Reflux; |
9.31 g 2-Fluoro-5-nitrotoluene (60 mmol) was dissolved in 100 ml carbon tetrachloride, 10.68 g N-bromosuccinimide (60 mmol) and 1.97 g 2,2?-Azobis(2-methyl)propionitrile (12 mmol) were added. Mixture was refluxed for two days. Then it was cooled to room temperature and the precipitated solid was filtered off. The filtrate was evaporated under reduced pressure and used up directly in the next step without any further purification or analytical investigation. Yield was considered as it had been 100percent. |
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