5-IODOISATIN

Uses

5-Iodoisatin undergoes condensation reaction with phenol yields 5-iodophenolisatin, malonic acid yields 6-iodo-2-quinolone-4-carboxylic acid.

Definition

ChEBI: 5-Iodoisatin is a member of indoles. It has a role as an anticoronaviral agent.

General Description

5-Iodoisatin undergoes condensation reaction with:

• phenol yields 5-iodophenolisatin
• malonic acid yields 6-iodo-2-quinolone-4-carboxylic acid

Synthesis

60313-92-0

20780-76-1

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).

References

[1] European Journal of Medicinal Chemistry, 2015, vol. 92, p. 818 - 838
[2] Tetrahedron, 2005, vol. 61, # 25, p. 6082 - 6087
[3] Medicinal Chemistry, 2016, vol. 12, # 5, p. 489 - 498
[4] Chemische Berichte, 1924, vol. 57, p. 1773
[5] European Journal of Pharmacology, 2007, vol. 556, # 1-3, p. 200 - 206