Introduction: The present study presents an effective one-pot protocol for the synthesis of triiodosubstituted aromatic (benzoic) acids – radiopaque analogues of amidotrizoic acid. For the production of the acids intended, I2/AgNO3 couple was used as an effective iodinating reagent. Moreover, suitably substituted methoxybenzoic acid derivatives were selected as appropriate targets for iodination. The total iodine content in the final (crude) products was determined by Volhard’s titrimetric method. Further details on the chemical structure of the reaction products were obtained by ATR-FTIR and 1H NMR spectroscopy.
Aim: The aim of the present study is to evaluate the effectiveness of a new method proposed for the synthesis of triiodo-substituted aromatic acids – analogues of the X-ray contrast amidotrizoic acid.
Materials and Methods: All necessary reagents and solvents for the study were purchased from Acros Organics, Fisher. The syntheses were performed under mild conditions using standard laboratory equipment. The infrared (IR) spectral instrument was a TENSOR II of Bruker (Germany), equipped with an ATR (Platinum) attachment. The total iodine content of the crude reaction products was assayed by a classical pharmacopoeial method.
Results: All aromatic acids were successfully iodinated with the reagent couple used. Unfortunately, it was found that the reaction products were mixtures of several compounds – partially and completely iodinated products. The presence of 2,6-diodosubstituted acids in them was established by the appearance of a ν(C=O) band in the shortwave range (at over 1700 cm-1). The total iodine content in the final (crude) products was determined by Volhard's back titration method.
Conclusion: The applied synthetic method allows the production of a mixture of partially and completely iodinated products, derivatives of the utilized aromatic acids – 3,4-dimethoxybenzoic (3,4-DMBA) and 3,5-dimethoxybenzoic acid (3,5-DMBA). The presence of 2,6-diodosubstituted acids in the products’ composition was determined using ATR FTIR spectroscopy. The reduced yield of the totally substituted products was associated with the lower activity of the iodinating reagent. However, the iodine content of one of the products thus obtained was found to be close to the expected triiodine one.
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