1. Preheat concentrated sulfuric acid (275 mL) at 60 °C. After stopping the heating, add p-iodoacetoacetanilide (22.0 g, 75.9 mmol) in batches with stirring, controlling the temperature to no more than 65 °C.
2. The reaction mixture was heated at 80 °C for 15 min.
3. After cooling to room temperature, it was further cooled to 0 °C and then the reaction mixture was slowly poured into crushed ice (550 g) and stirred at 0 °C for 1 hour.
4. The orange colored precipitate formed was collected by filtration and washed with water (110 mL).
5. Dissolve the precipitate in preheated 10% aqueous sodium hydroxide solution (55 mL, 60 °C).
6. Acetic acid (16.5mL) was added and heated at 60°C for 30 minutes.
7. After cooling to room temperature, further cooled to 0 °C, the precipitate was collected by filtration, washed with water (11 mL) and dried under vacuum to give 5-iodoindigo (17.1 g, 62.7 mmol) as an orange solid.
8. Yield 83%; melting point 272-274 °C (literature value: 272-274 °C); IR (KBr) ν 1198, 1458, 1606, 1731-1751, 3241 cm-1; 1H NMR (200 MHz, DMSO-d6) δ 6.75 (d, 1H, J=8.2 Hz, H-7), 7.76 (d, 1H. J=1.8Hz, H-4), 7.88 (dd, 1H, J=1.8,8.2Hz, H-6), 11.11 (s, 1H, NH); 13C NMR (50MHz, DMSO-d6) δ 85.8 (C-5), 115.2 (C-7), 120.4 (C-3a), 132.9 (C-4), 142.0 (C 6), 150.7 (C-7a), 159.3 (C-2), 183.7 (C-3).
