High yield synthesis of trans-Azoxybenzene versus 2-isopropoxy-4-nitrobenzoic acid: Influence of temperature and base concentration

The reported two-step synthesis of 2-isopropoxy-4-nitrobenzoic acid from 2-hydroxy-4-nitrobenzoic acid, using iodopropane/K2CO3 and subsequent hydrolysis of the isopropyl 2-isopropoxy-4-nitrobenzoate intermediate with 45% NaOH/THF-EtOH at 80 °C, was reconsidered. (Z)-1,2-bis(4-carboxy-3-isopropoxyphenyl)diazene-1-oxide derivative (3), which was isolated as main product (92%) of the reaction, was characterized by IR, 1H, 13C, and 15N NMR spectroscopy. The 15N chemical shifts were consistent with the trans-configuration for this azoxybenzene derivative. As an alternative, synthesis of 2-isopropoxy-4-nitrobenzoic acid was accomplished in high yield (82%) working at room temperature and using lithium hydroxide instead of concentrate NaOH. Incorrect reaction temperature report or measurement in the published protocol (J. Org. Chem. 2011, 76, 7040) probably accounts for the discrepancies with our findings.