Synthesis
At room temperature, 1.0 g (8.18 mmol) of 3-hydroxybenzaldehyde was dissolved in 100 mL of dichloromethane, and 1.078 g (12.28 mmol) of HBF4-OEt2 was slowly added, followed by 3.045 g (8.18 mmol) of IPy2BF4 (bis(pyridinium)iodonium(I) tetrafluoroborate). The reaction mixture was stirred at room temperature for 5 min before adding 15 mL of 1M HCl aqueous solution. The aqueous phase was extracted with dichloromethane (3 x 10 mL), the organic phases were combined and washed sequentially with 10 mL of water and 25 mL of 5% aqueous sodium thiosulfate and dried over anhydrous sodium sulfate. The solvent was removed by concentration under reduced pressure to give a brown solid. The solid was purified by recrystallization from chloroform to give 443 mg (22% yield) of 5-hydroxy-2-iodobenzaldehyde as a brown solid with a melting point of 130-132°C (ignition melting point 125-126°C).
1H NMR (300 MHz, CD3COCD3): δ 9.96 (s, 1H), 9.15 (s, 1H), 7.85 (d, J = 8.6 Hz, 1H), 7.34 (d, J = 3.1 Hz, 1H), 6.98 (dd, J1 = 8.5 Hz, J2 = 3.1 Hz, 1H).
1H NMR (300 MHz, CDCl3): δ 9.99 (s, 1H), 7.79 (d, J = 8.4 Hz, 1H), 7.45 (d, J = 3.0 Hz, 1H), 6.91 (dd, J1 = 8.4 Hz, J2 = 3.0 Hz, 1H), 6.18 (br s, 1H).
13C NMR (75 MHz, CD3COCD3): δ 196.6 (CHO), 160.1 (C-5), 143.3 (C-3), 137.9 (C-1), 125.4 (C-4), 118.1 (C-6), 88.5 (C-2); 13C NMR (75 MHz, CD3COCD3): δ 196.6 (CHO), 160.1 (C-5), 143.3 (C-3), 137.9 (C-1), 125.4 (C-4), 118.1 (C-6), 88.5 (C-2)
13C NMR (75 MHz, CDCl3): δ 196.3 (CHO), 156.7 (C-5), 141.4 (C-3), 135.7 (C-1), 123.9 (C-4), 116.5 (C-6), 89.4 (C-2).
HRMS (EI) m/z: [M]+ calcd for C7H5IO2: 247.9334; found: 247.9292.
References
[1] Organic Preparations and Procedures International, 2017, vol. 49, # 3, p. 265 - 272
[2] Journal of the Chemical Society, 1937, p. 76
[3] Journal of the Indian Chemical Society, 1952, vol. 29, p. 363,364
[4] Journal of Medicinal Chemistry, 1973, vol. 16, p. 684 - 687
[5] Patent: WO2016/55947, 2016, A1. Location in patent: Page/Page column 70
