Application of 556-96-7, These common heterocyclic compound, 556-96-7, name is 1-Bromo-3,5-dimethylbenzene, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
Magnesium turnings (5.10 g, 210 mmol, 6 equiv) were washed with hexanes and dried in a 120 C oven for 1 h. The vacuum. Upon cooling to room temperature, a small amount of iodine (50 mg) was added to the flask, and the solids were suspended in THF (120 mL). The flask was fitted with a reflux condenser, then vacuum purged/backfilled with nitrogen three times, and warmed to 50 C in an oil bath. A vent needle was added at the top of the reflux condenser to allow rapid gas release during the initiation of Grignard formation. Neat 3,5-dimethylbromobenzene (14.3 mL, 105 mmol, 3 equiv) was then added at a slow dropwise pace. Formation of the Grignard reagent was indicated by the disappearance of the dark brown THF-iodine adduct, at which point the addition was halted until a controlled, gentle reflux was obtained, and the vent needle was removed. Dropwise addition of the bromide was resumed so as to maintain a gentle reflux. After the addition was complete, the solution was stirred at 50 C for 30 mm, then removed from its bath and cooled to 0 C in an ice/water bath. Diethyl phosphite (4.5 mL, 35 mmol, 1 equiv) was added at a fast dropwise pace, and the solution was stirred at 0 C for 1 h. At this time, the reflux condenser was replaced with an addition funnel, and ice cold 6M HC1 (40 mL, prepared by mixing 20 g ice with 20 mL concentrated HC1) was added at a slow dropwise pace. 300 mL water was added and the solution was stirred vigorously for 1 h. The layers were separated and the aqueous phase was thrice extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated. The product was purified by column chromatography (1-3-5% MeOH/DCM). White solid, 7.58 g, 29.3 mmol, 84% yield. NMR spectra were identical to the previously isolated compound.??H NMR (300 MHz, CDC13) oe 7.94 (d, J 477 Hz, 1H), 7.32 (dt, J 1.5, 0.7 Hz, 2H), 7.28 (dt, J= 1.6, 0.7 Hz, 2H),7.17 (tp, J 1.7, 0.8 Hz, 2H), 2.34 (p, J= 0.6 Hz, 12H); 3?P NMR (121 MHz, CDC13) o 22.71.
Statistics shows that 1-Bromo-3,5-dimethylbenzene is playing an increasingly important role. we look forward to future research findings about 556-96-7.
Reference:
Patent; CALIFORNIA INSTITUTE OF TECHNOLOGY; STOLTZ, Brian, M.; WELIN, Eric, R.; VIRGIL, Scott, C.; TADROSS, Pamela; POTOTSCHNIG, Gerit, Maria; NGAMNITHIPORN, Aurapat (Fa); NEGORO, Kenji; LAPOINTE, Guillaume; KLATTE, Max; HALEY, Christopher; GRUENANGER, Christian; GLIBSTRUP, Emil; GILMORE, Christopher; ALLAN, Kevin, McCormack; (114 pag.)WO2019/18539; (2019); A1;,
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