Toluene → 5-Bromo-3-cyanoindole

Participants

Reaction Steps

Hydroxylamine hydrochloride (4.5 g, 66 mmol) is add to a mixture of 5-bromoindole-3-carbaldehyde (14.7 g, 66 mmol, reference example 74) and methanol (100 mL). After 1 hour toluene (80 mL) and THF (30 mL) are added and the reaction concentrated. Additional toluene (80 mL) is added and the reaction is azeotroped again. The mixture is dissolved in toluene (200 mL) and thionyl chloride (12 mL, 165 mmol) added causing a mild exotherm. The reaction is placed in a 70° C. bath and heated for 45 minutes. The reaction is then cooled and azeotroped with a mixture of CH2Cl2 and THF. The crude reaction mixture is dissolved in a mixture of methanol and CH2Cl2, adsorbed to silica gel and extracted with CH2Cl2 to provide 11.4 g of 5-bromoindole-3-carbonitrile. An analytically pure sample is obtained by recrystallization from toluene: (reddish needles) m.p. 189-191; 1H NMR (300 MHz, DMSO-d6) d 12.38 (bs, 1H), 8.30 (d, J=3.0 Hz, 1H), 7.79 (d, J=1.5 Hz, 1H), 7.52 (d, J=8.6 Hz, 1H), 7.40 (dd, J=8.6, 1.6 Hz, 1H); MS (EI) m/z 220 (M+, Br).

Provenance & Evidence