4-Hydroxybenzoic Acid → 4-Hydroxy-3-iodobenzoic acid (2IPCOOH)

Participants

Reaction Conditions

Reaction Steps

4-Hydroxybenzoic acid (34.5 g, 250 mmol) is suspended in MeOH (500 mL), treated with NaI (34.5 g, 250 mmol) and NaOH (20 g, 500 mmol) and cooled to 0° C. Sodium hypochlorite (Clorox bleach) (423 mL, 250 mmol) is added slowly drop-wise at 0-5° C. and the mixture is stirred for 1 h. The mixture is treated with saturated Na2S2O3 (135 mL) and water (135 mL) and stirred overnight as the cooling bath expired. The mixture is acidified to pH 3.5 with concentrated HCl and the resulting precipitate filtered off. The solid contained a mixture of the desired mono-iodo product and the iodo-chloro and the bis-iodo byproducts; it is discarded. The filtrate is concentrated to dryness, partitioned between H2O (300 mL) and EtOAc (1×500 mL, then 3×300 mL), dried (Na2SO4) and concentrated to afford 59.6 g (90%) of 4-hydroxy-3-iodobenzoic acid as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 6.95, 7.80, 8.22 ppm.

Provenance & Evidence