Carbon Dioxide → 4-Bromo-2,5-difluorobenzoic acid

Participants

Reaction Conditions

Reaction Steps

Freshly titrated n-butyl lithium (27.0 ml, 1.39 M in hexanes) is added slowly (over about 30 minutes) to a −78° C. solution of diethyl ether (90 ml) containing 1,4-dibromo-2,5-difluorobenzene (1, 10.22 g, 0.038 mol). The resulting yellow solution is stirred at −78° C. for 2 hours to give a yellow suspension. Several pellets (˜10) of dry ice are added to the suspension, which is then allowed to warm slowly to room temperature as it degasses (approximately 40 minutes). The resulting suspension is acidified with a 1 M aqueous solution of hydrochloric acid (500 ml), and the product extracted with diethyl ether (5×200 ml). The combined organics are washed with water (4×100 ml) and filtered. The ether solution is concentrated to approximately 200 ml under reduced pressure, and the product extracted into a saturated aqueous solution of sodium bicarbonate (3×200 ml). The combined aqueous extracts are washed with methylene chloride (3×100 ml) and acidified with hydrochloric acid. The product is extracted with diethyl ether (3×200 ml), and the combined organic extracts washed with water (2×200 ml), dried over magnesium sulfate, and concentrated under reduced pressure to give (2) as a pale yellow solid. 1H NMR (300 MHz, DMSO-d6): δ 7.74 (dd, JH-F=8.5 Hz, 6.5 Hz, 1H), 7.84 (dd, JH-F=10.0 Hz, 5.5 Hz, 1H), 13.7 (br, 1H, CO2H). 19F{1H} NMR (282 MHz, DMSO-d6): δ −114.0 (d, JF-F=17.0 Hz, 1F), −113.6 (d, JF-F=17.0 Hz, 1F). 13C{1H} NMR (75 MHz, DMSO-d6): δ 113.6 (dd, JC-F=23.5 Hz, 10.0 Hz), 118.4 (dd, JC-F=26.5 Hz, 2.5 Hz, CH), 120.0 (dd, JC-F=19.0 Hz, 12.0 Hz), 122.2 (d, JC-F=28.0 Hz, CH), 154.4 (dd, JC-F=245.0 Hz, 5.5 Hz, CF), 156.8 (dd, JC-F=251.5 Hz, 4.0 Hz, CF), 163.4 (m, CO2H).

Provenance & Evidence