2-Iodobenzoic acid: properties and applications in organic synthesis

General Description

2-Iodobenzoic acid is a white solid compound with a melting point of 230-233°C. It is slightly soluble in water but readily dissolves in organic solvents like ethanol and acetone. This compound is used as a precursor in the synthesis of various organic compounds due to its reactivity towards nucleophiles, making it useful in substitution reactions. It can also undergo decarboxylation under specific conditions. 2-Iodobenzoic acid finds applications in the synthesis of 3-substituted isocoumarins, indoles, and hypervalent iodine reagents. These applications allow for the creation of diverse organic compounds with specific functionalities. The compound's versatility and reactivity make it valuable in organic synthesis.

Figure 1. 2-Iodobenzoic acid

Properties

2-Iodobenzoic acid is a white solid compound with the chemical formula C7H5IO2. It has a melting point of 230-233°C and is slightly soluble in water. This compound is primarily used as a precursor for the synthesis of various organic compounds. It exhibits strong reactivity towards nucleophiles, making it useful in substitution reactions. Additionally, 2-Iodobenzoic acid can undergo decarboxylation under specific conditions, which can be utilized in decarboxylation reactions or as a means of removing the carboxyl group from the molecule. It is sparingly soluble in water but readily dissolves in organic solvents such as ethanol and acetone. However, it is important to handle and store this compound carefully as it may be sensitive to moisture and light. Overall, 2-Iodobenzoic acid is a valuable compound in organic synthesis due to its reactivity and versatility. ¹

Applications in organic synthesis

Synthesis of 3-substituted isocoumarins

2-Iodobenzoic acid has proven to be a useful substrate for the synthesis of 3-substituted isocoumarins, which are present in various natural products with diverse biological activities. In a study, a mesoporous CuO@MgO nanocomposite was prepared via the sugar-blowing induced confined method and was found to have excellent catalytic potential in the facile synthesis of 3-substituted isocoumarin from 2-iodobenzoic acids and terminal alkynes. The nanocomposite exhibited a broad substrate scope, mild reaction conditions, and excellent yield in a short reaction time, without the use of additives, and with better green chemistry metrices such as a low E-factor, high reaction mass efficiency, low process mass efficiency, and high turnover number. Moreover, the nanocatalyst was recycled and reused up to five runs without significant loss in catalytic activity and very low leaching of copper and magnesium ions. This study demonstrates the potential of using 2-iodobenzoic acid in the synthesis of 3-substituted isocoumarins and highlights the beneficial properties of the mesoporous CuO@MgO nanocomposite as a recyclable and efficient catalyst. ²

Synthesis of indoles

2-Iodobenzoic acid is a valuable reagent widely utilized in the synthesis of indoles. One prominent application of 2-Iodobenzoic acid is its involvement in the Pictet-Spengler reaction. This transformation involves the condensation of an aryl aldehyde or ketone with a tryptamine derivative, leading to the formation of indole derivatives with excellent regioselectivity. By utilizing 2-Iodobenzoic acid as a reactant in the Pictet-Spengler reaction, chemists can selectively introduce the iodine substituent onto the indole ring, providing access to a broad range of iodinated indole compounds. Furthermore, 2-Iodobenzoic acid can be used in the synthesis of indoles through transition-metal-catalyzed C-H activation reactions. In these transformations, the iodine atom serves as a directing group, facilitating the selective functionalization of C-H bonds adjacent to the carboxylic acid group. In summary, 2-Iodobenzoic acid proves to be a valuable reagent in the synthesis of indoles, enabling chemists to access a wide range of iodinated indole compounds through Pictet-Spengler reactions and transition-metal-catalyzed C-H activation reactions. ³

Synthesis of hypervalent iodine

2-Iodobenzoic acid has been successfully used in the synthesis of a novel type of hypervalent iodine reagents called vinylbenziodoxolones (VBX). These reagents are synthesized in a one-pot reaction using 2-iodobenzoic acid as a starting material. VBX exhibits excellent stability and its cyclic structure has been confirmed through X-ray analysis. The reactivity of VBX has been investigated in vinylation reactions, specifically in the vinylation of nitrocyclohexane. Interestingly, VBX demonstrates regioselectivity different from acyclic vinyl(aryl)iodonium salts, producing vinylated products with opposite regioselectivity. This unique reactivity makes VBX a promising tool for vinylation reactions under both metal-free and metal-catalyzed conditions. The development of these hypervalent iodine reagents opens up new possibilities for the synthesis of vinylated compounds and expands the toolbox of available reactions in organic synthesis. ⁴

Reference

1. Santos LM, And AN, Kingswood M. Biodegradation of 2-, 3- and 4-iodobenzoic acids. Journal of Chemical Technology and Biotechnology, 1999.

2. Rawat M, Rawat DS. Mesoporous Copper-Magnesium Oxide Hybrid Nanocatalyzed Synthesis of 3-Substituted Isocoumarins from 2-Iodobenzoic Acid and Terminal Alkyne under Green Conditions. ACS Omega, 2023, 8(18):16263-16272.

3. Leogane O, Lebel H. One-pot multicomponent synthesis of indoles from 2-iodobenzoic acid. Angew Chem Int Ed Engl, 2008, 47(2):350-352.

4. Stridfeldt E, Seemann A, Bouma MJ, Dey C, Ertan A, Olofsson B. Synthesis, Characterization and Unusual Reactivity of Vinylbenziodoxolones-Novel Hypervalent Iodine Reagents. Chemistry, 2016, 22(45):16066-16070.

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