Iodine(III)‐Mediated Free‐Aniline Iodination through Acetyl Hypoiodite Formation: Study of the Reaction Pathway

Abstract

In memory of KevinThe first iodine(III)-mediated para-selective iodination protocol for free anilines as well as the mechanistic elucidation of the reaction pathway is described. The developed method proceeded under clean, non-toxic, efficient, and in general mild reaction conditions. To the best of our knowledge this report describes for the first time a procedure focused specifically on the introduction of an iodine atom in free anilines using PIDA [(diacetoxyiodo)benzene] and ammonium iodide which formed in situ acetyl hypoiodite (AcO-I) as the halogenating species. Our DFT calculations suggest a reaction mechanism that highlights the catalytic role of the ammonium cation in the AcO-I formation and halogenation. Considering there are few procedures for the iodine atom introduction in anilines using non-acidic conditions, herein we described an initial report on a mild and operationally simple alternative using iodine(III) reagents.

Iodine(III)‐Aluminum or ‐Ammonium Salts for the Oxidative Aromatic Inorganic Functionalization

“…The use of our protocol allowed the iodination of some phenol-ethers (118)(119)(120), aromatic aldehydes and ketones (121,122) and different heterocycles such as 1,3-benzodioxole, dibenzofuran, indole and carbazole (123)(124)(125)(126). Nevertheless, as part of the scope, when the iodinating system was used in very electron-deficient aryls containing the À NO 2 group, no reaction was found.…”

“…In such a way, a protocol which resulted in a para selective iodination was developed. [123] Thus, different iodine(III) and iodine atom sources were explored. We focused on finding cheap and commercially available reagents.…”

“…The final contribution herein presented about the iodination using λ 3 ‐iodanes, was focused on non‐protected or nitrogen‐free anilines. In such a way, a protocol which resulted in a para selective iodination was developed [123] . Thus, different iodine(III) and iodine atom sources were explored.…”

Synthesis and Anti‐inflammatory Effect of Simple 2,3‐Diarylindoles. On Route to New NSAID Scaffolds

“…[4] Concerning this research, nitrogen-containing compounds, specifically those with the indole core, are among the most important group of heterocycles which are present in hundreds of pharmacological active drugs and treatments. [5][6][7][8][9][10][11] Synthetic methods for accessing to this class of active compounds involves in general, the use of metal free [12][13][14][15][16][17][18][19][20][21][22][23][24] or metal catalyzed [25,26] strategies. In the context of this work, we referred to indomethacin, as an indole-containing drug, considered one of the most efficient anti-inflammatories which acts as nonselective COX-1 and COX-2 inhibitor.…”

Synthesis andin vivoEvaluation of Fluorobenzyl Metformin Derivatives as Potential Drugs in The Diabetes Treatment

“…Organic chemistry is, among the scientific disciplines, the most used tool to obtain treatments for clinical and/or biological affections. This discipline has been evolving with time, increasing the development of compounds with high pharmaceutical interest, using strategies such as metal-catalyzed, [1,2] metalfree [3][4][5][6][7][8][9][10] or natural occurring compounds synthesis and derivatization. [11][12][13] These compounds have been developed with specific goals, such as for the treatment of cancer, [14,15] mycoses, [16] polycystic ovarian, pain, inflammation [17] hyper-glycemia and lastly but not less important: diabetes mellitus.…”