5-Iodo-2-methyl anisole
[CAS# 220728-62-1]

Identification

• Classification: Flavors and spices >> Synthetic spice >> Phenols, ethers and epoxides
• Name: 5-Iodo-2-methyl anisole
• Synonyms: 4-iodo-2-methoxy-1-methylbenzene
• Molecular Formula: C₈H₉IO
• Molecular Weight: 248.06
• CAS Registry Number: 220728-62-1
• SMILES: CC1=C(C=C(C=C1)I)OC

Properties

• Density: 1.6±0.1 g/cm³ Calc.^*
• Boiling point: 255.2±20.0 ºC 760 mmHg (Calc.)^*
• Flash point: 108.2±21.8 ºC (Calc.)^*
• Index of refraction: 1.582 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H315-H319-H335
• Precautionary Statements: P261-P264-P271-P280-P302+P352-P304+P340+P312-P305+P351+P338-P332+P313-P337+P313-P362-P403+P233-P405-P501

Discovory and Applicatios

5-Iodo-2-methyl anisole is an aromatic organic compound that belongs to the class of substituted anisoles. It contains a methoxy group (-OCH₃) attached to a benzene ring, along with a methyl group (-CH₃) and an iodine atom. The precise substitution pattern places the methoxy group at the 1-position, the methyl group at the 2-position, and the iodine atom at the 5-position of the aromatic ring. The molecular structure of this compound can be represented as C₈H₉IO, and it exists as a colorless to pale yellow solid or liquid, depending on temperature and purity.

The synthesis of 5-iodo-2-methyl anisole is typically achieved through electrophilic aromatic iodination of 2-methyl anisole (also known as o-cresyl methyl ether). The introduction of the iodine atom at the 5-position is directed by the electron-donating effects of both the methoxy and methyl substituents, which influence the regioselectivity of the halogenation reaction. Iodination is commonly carried out using iodine (I₂) in the presence of an oxidizing agent such as nitric acid (HNO₃) or hydrogen peroxide (H₂O₂), though alternative methods may employ N-iodosuccinimide (NIS) under milder conditions.

This compound serves primarily as an intermediate in organic synthesis. The iodine atom in the aromatic ring offers a reactive site for palladium-catalyzed cross-coupling reactions, such as the Suzuki-Miyaura and Sonogashira couplings, which are frequently used in the formation of carbon-carbon and carbon-heteroatom bonds. These transformations are instrumental in the preparation of more complex molecules, including functionalized aromatic compounds and heterocycles.

In medicinal chemistry, 5-iodo-2-methyl anisole has been used as a precursor in the development of biologically active molecules. Its structure allows for further functionalization to produce analogs of natural products, pharmaceutical candidates, or radiolabeled compounds. Although the compound itself is not used as a drug or therapeutic agent, its role as a versatile building block contributes to the construction of molecular frameworks found in bioactive substances.

Additionally, 5-iodo-2-methyl anisole has found application in the synthesis of ligands and probes for chemical biology. The presence of both the methoxy and methyl groups contributes to the electronic characteristics of the molecule, while the iodine atom can be replaced with various substituents or used in isotopic labeling studies. For instance, incorporation of iodine-125 allows its use in radiochemical studies or receptor binding assays.

Beyond medicinal chemistry, derivatives of 5-iodo-2-methyl anisole are also investigated in materials science. Aromatic iodides, including this compound, can participate in the synthesis of functionalized polymers and organic semiconductors. These materials often require precise molecular architecture, which is facilitated by the selective reactivity of the iodo group under cross-coupling conditions.

Due to its relatively simple structure and synthetic accessibility, 5-iodo-2-methyl anisole continues to be employed in the development of new synthetic methodologies, especially those involving halogenated aromatic compounds. Its utility lies in its predictable reactivity and the ability to serve as a platform for further derivatization, making it valuable in both academic and industrial chemical research.

References

2015. Fluoroalcohol-mediated reductive iodonio-Claisen rearrangement: Synthesis of complex ortho-substituted-allyl iodoarenes. Frontiers of Chemical Science and Engineering, 9(3).
DOI: 10.1007/s11705-015-1530-6

2009. Intramolecular Friedel-Crafts-Type alpha-Arylation of Aldehydes. Synfacts, 2009(4).
DOI: 10.1055/s-0028-1088099