Compound Overview and Chemical Properties

Methyl 5-iodo-2,4-dimethylbenzoate (SKU: M732240; molecular formula C₁₀H₁₁IO₂; MW ≈ 290.10 g/mol) is an aryl iodide building block featuring a methyl ester at the 1-position and methyl substituents at the 2- and 4-positions of the benzene ring, with an iodo group at the 5-position. The carbon–iodine bond is notably weaker and more polarizable than C–Br or C–Cl bonds, making this compound an exceptionally reactive electrophile toward oxidative addition into low-valent palladium(0) and other transition-metal complexes. The flanking methyl groups introduce steric and electronic effects that can be exploited to control regioselectivity in downstream transformations. The ester moiety provides an additional handle for further functionalization via hydrolysis, reduction, or amide coupling.

The compound typically appears as a white to off-white crystalline solid and should be handled as a potential irritant. No specific melting point or boiling point data are confirmed from the source material; researchers should consult the certificate of analysis (CoA) supplied with the product lot.

Safety, Storage, and Handling

Personal Protective Equipment (PPE): Wear appropriate chemical-resistant gloves (e.g., nitrile), safety goggles, and a laboratory coat when handling this compound. Work in a well-ventilated fume hood to minimize inhalation exposure to dust or vapors.

Storage: Store in a tightly sealed container in a cool (2–25 °C recommended), dry location away from direct light and incompatible oxidizing agents. An inert atmosphere (nitrogen or argon) is advisable for long-term storage to prevent moisture absorption and potential oxidative degradation of the aryl iodide.

Waste Disposal: Dispose of all waste containing this compound in accordance with local institutional and governmental regulations for halogenated organic waste streams.

First Aid: In case of skin contact, wash thoroughly with soap and water. In case of eye contact, flush immediately with copious water and seek medical attention. If inhaled, move to fresh air.

Note: Specific GHS hazard classifications and R/S phrases should be verified from the Safety Data Sheet (SDS) supplied by Aladdin Scientific for lot M732240.

Protocol: Use in Palladium-Catalyzed Cross-Coupling Reactions

The following is a general procedural guide for using Methyl 5-iodo-2,4-dimethylbenzoate as an aryl halide electrophile in Pd-catalyzed cross-coupling reactions (e.g., Suzuki–Miyaura, Sonogashira, Negishi). Researchers should optimize conditions for their specific substrate and coupling partner.

1. Reaction Setup: Flame-dry or oven-dry all glassware and cool under an inert atmosphere (N₂ or Ar). Charge the reaction vessel with Methyl 5-iodo-2,4-dimethylbenzoate (1.0 equiv), the appropriate nucleophilic coupling partner (e.g., boronic acid for Suzuki; terminal alkyne for Sonogashira; organozinc for Negishi), Pd catalyst (e.g., Pd(PPh₃)₄ or Pd(dppf)Cl₂, 1–5 mol%), ligand if required, and base (e.g., K₂CO₃, Cs₂CO₃, or Et₃N depending on reaction type).
2. Solvent: Select an appropriate anhydrous solvent (e.g., DMF, THF, dioxane, or toluene). Degas the solvent by sparging with inert gas or freeze-pump-thaw cycles before use.
3. Reaction Conditions: Heat the reaction mixture to the recommended temperature (typically 60–100 °C) and monitor by TLC or LCMS. The highly reactive C–I bond generally permits milder conditions and shorter reaction times compared to the analogous aryl bromide or chloride.
4. Workup: After completion, cool the mixture to room temperature, dilute with ethyl acetate or another suitable solvent, wash with aqueous base and brine, dry over anhydrous MgSO₄ or Na₂SO₄, filter, and concentrate under reduced pressure.
5. Purification: Purify the crude product by column chromatography (silica gel), recrystallization, or other suitable techniques. Characterize the product by ¹H NMR, ¹³C NMR, and MS.

Specific reaction conditions, yields, and catalyst loadings should be optimized empirically and verified against published literature for analogous substrates.

Applications in Directed Metalation and Further Functionalization

Beyond cross-coupling, Methyl 5-iodo-2,4-dimethylbenzoate can participate in directed ortho-metalation (DoM) strategies. The ester group acts as a directed metalation group (DMG), coordinating with organolithium or other strong base reagents to position deprotonation at specific ortho sites. However, the aryl iodide is susceptible to lithium–halogen exchange under standard DoM conditions (n-BuLi or t-BuLi), which can be strategically exploited to generate a highly reactive aryllithium intermediate at the 5-position for subsequent electrophilic trapping with aldehydes, ketones, CO₂, or other electrophiles.

The methyl ester can be further transformed by:

• Saponification to the corresponding carboxylic acid using aqueous NaOH or LiOH.
• Reduction to the benzyl alcohol using LiAlH₄ or DIBAL-H.
• Conversion to amides via ester aminolysis or activation (e.g., with oxalyl chloride) followed by reaction with amines.

These orthogonal handles make this compound a flexible platform for multi-step synthesis of pharmacophores, agrochemical intermediates, and functional materials.

Quality, Purity, and Analytical Verification

Researchers should verify the identity and purity of each lot of Methyl 5-iodo-2,4-dimethylbenzoate (M732240) before use. Recommended analytical checks include:

• ¹H NMR: Confirm the characteristic aromatic proton signals and the methyl ester singlet (typically ~3.9 ppm), along with the two aromatic methyl groups and a single aromatic H in the expected positions.
• GC or HPLC Purity: A purity ≥97% is typical for research-grade material. Consult the lot-specific CoA provided by Aladdin Scientific.
• Elemental Analysis or HRMS: Confirm empirical formula C₁₀H₁₁IO₂ and exact mass.
• Melting Point: Verify against the value listed on the CoA (specific value not confirmed in source material; flag for review).

Store remaining material under inert atmosphere at cool temperature and re-verify purity if the compound has been stored for an extended period before use in sensitive applications.