INTRODUCTION: Both iodo-substituted aromatic hydrocarbons and their more complex derivatives (phenols, aromatic acids, carbaldehydes, and others) are currently being used with unquestionable success in organic and pharmaceutical synthesis. Rationally, the design of a wide variety of polysubstituted biphenyl, stilbene, and other derivatives can be successfully accomplished using these compounds. As a continuation of our previous work, we propose a much more convenient and feasible methodology for the synthesis of the polysubstituted diiodo-containing 2,6-diiodo-3,4,5-trimethoxybenzoic acid.
AIM: The aim of this article is to demonstrate the suitability of the used reagent pair, I2/AgNO3, in the iodination of the natural 3,4,5-trimethoxybenzoic (eudesmic) acid in the presence of water.
MATERIALS AND METHODS: For the synthesis of the principal, a green strategy was applied, which used the commonly available and biocompatible reagents iodine, silver nitrate, methanol, and water. The suitability of the applied synthetic methodology was determined by the purity of the reaction product. The latter was established through Fourier transform infrared (FTIR) and 1H nuclear magnetic resonance (NMR) analysis.
RESULTS: The presence of a small amount of water in the reaction mixture did not alter the yield and purity of the desired reaction product, 2,6-diiodo-3,4,5-trimethoxybenzoic acid. In all probability, the in situ-formed iodine nitrate (INO3) preserved its activity in an aqueous environment. The quantitative conversion of the organic reactant used can also be taken as indirect evidence of the stability of the thus obtained INO3.
CONCLUSION: The presented preparative methodology holds potential as an optimal choice in the synthesis of the target 2,6-diiodo-3,4,5-trimethoxybenzoic acid. Given its feasibility and use of commonly available reagents, the presented synthetic strategy can be easily implemented by novice chemists, including students.
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