[Synthesis]
Synthesis of 4-fluoro-2-iodobenzoic acid (11): 4-fluoro-2-iodobenzaldehyde (10) (2.82 g, 11.3 mmol) was dissolved in a mixed solvent of H2O (500 mL) and acetone (90 mL), to which were added sequentially H2NSO3H (1.59 g, 16.4 mmol) and NaClO2 (1.78 g, 15.7 mmol, technical grade (80% purity). The reaction mixture was stirred at room temperature for 3.5 h. The progress of the reaction was monitored by thin layer chromatography (TLC) until complete consumption of the ingredients. Upon completion of the reaction, the aqueous phase was extracted with ethyl acetate (EtOAc, 4×), the organic phases were combined, washed with saturated saline, and concentrated under reduced pressure to afford the colorless solid product 11 (2.55 g, 9.6 mmol, 85% yield). The product was characterized by the following data: melting point 155-157 °C; TLC Rf = 0.5 (CHCl3-MeOH = 10:1, v/v); IR (KBr, cm-1): 3436 (br), 3070 (br), 1701 (s), 1588 (s), 1575 (s), 1477 (m), 1413 (m), 1303 (s). 1260 (s), 1206 (s), 1030 (m), 874 (m), 605 (m); 1H NMR (300 MHz, CD3OD): δ 7.23-7.29 (m, 1H), 7.82 (dd, 3JHF = 8.4 Hz, 4JHH = 2.6 Hz, 1H), 7.90 (dd, 3JHH = 8.7 Hz, 4JHH = 2.6 Hz, 1H), 7.90 (dd, 3JHH = 8.7 Hz, 4JHH = 6.0 Hz), 7.90 (dd, 3JHH = 8.7 Hz, 4JHH = 2.6 Hz, 1H) 4JHF = 6.0 Hz, 1H); 13C NMR (75.5 MHz, CD3OD): δ 95.4 (d, 3JCF = 8.5 Hz), 116.4 (d, 2JCF = 21.7 Hz), 129.7 (d, 2JCF = 24.1 Hz), 133.8 (d, 4JCF = 3.5 Hz), 134.0 (d, 3JCF = 9.1 Hz), 164.9 (d, 1JCF = 255.7 Hz), 169.0; MS (EI) m/z (relative intensities): 267 (27) [M+ + H], 266 (100) [M+], 249 (75) [C7H3OFI+], 221 (13) [C6H3FI+], 127 (2) [I+]. 122 (3) [C7H3OF+], 94 (17) [C6H3F+]; HRMS (EI) calculated value C7H4O2FI [M+] 265.9240, measured value 249.9258. |