Methyl 3-Iodo-1H-Indole-6-Carboxylate: Lab Handling Guide
Methyl 3-Iodo-1H-Indole-6-Carboxylate: Lab Handling Guide
Methyl 3-iodo-1H-indole-6-carboxylate is a halogenated indole building block valued in medicinal chemistry and materials science for its electrophilic C-3 iodo substituent and ester handle, which together enable versatile cross-coupling and further functionalization reactions.
- Chemical Name
- Methyl 3-iodo-1H-indole-6-carboxylate
- SKU
- M710164
- Molecular Formula
- C10H8INO2
- Molecular Weight
- 301.08 g/mol
- Key Functional Groups
- C-3 iodo substituent, methyl ester, NH indole
- Primary Application
- Synthetic intermediate for cross-coupling reactions and medicinal chemistry
- Storage Recommendation
- Cool, dry, dark conditions; store under inert atmosphere if opened
Chemical Identity and Physical Properties
Methyl 3-iodo-1H-indole-6-carboxylate (Aladdin SKU: M710164) is a bifunctionally substituted indole derivative. Its molecular formula is C10H8INO2 with a molecular weight of approximately 301.08 g/mol. The compound features an iodine atom at the C-3 position of the indole ring system—a site known for high reactivity toward palladium- and copper-catalyzed cross-coupling reactions—and a methyl ester group at the C-6 position, providing an additional handle for further chemical elaboration.
The compound is typically obtained as a solid. Like most iodinated aromatic compounds, it has relatively low volatility. The indole NH proton renders it susceptible to N-alkylation or N-protection strategies when reaction conditions require. Researchers should confirm purity by HPLC or NMR prior to use in sensitive synthetic sequences.
Storage, Stability, and Safe Handling
Store Methyl 3-iodo-1H-indole-6-carboxylate in a cool, dry, and well-ventilated location away from direct light. Upon opening, it is advisable to re-seal the container under an inert atmosphere (nitrogen or argon) to minimize moisture uptake and prevent slow oxidative degradation, which is a general concern for iodinated organic compounds. The compound should be kept away from strong oxidizers, strong bases, and reducing agents.
When handling, wear appropriate personal protective equipment including gloves, safety glasses, and a laboratory coat. Operations that could generate dust should be conducted in a chemical fume hood. Iodinated compounds, while generally less acutely toxic than their bromo or chloro analogs in many cases, should still be treated with standard precautions. Consult the Safety Data Sheet (SDS) supplied with the product before use. In the event of skin contact, wash thoroughly with soap and water. Do not dispose of via drain; follow institutional hazardous waste disposal procedures.
Solubility and Reconstitution
Methyl 3-iodo-1H-indole-6-carboxylate is expected to show good solubility in common polar aprotic organic solvents such as dimethyl sulfoxide (DMSO), dimethylformamide (DMF), and tetrahydrofuran (THF), consistent with the behavior of related methyl indole-carboxylate derivatives. Solubility in dichloromethane (DCM) and ethyl acetate is also anticipated. Aqueous solubility is expected to be low due to the hydrophobic indole scaffold and lipophilic iodo substituent.
For stock solution preparation, dissolve the compound in dry DMSO or DMF at the desired concentration. It is recommended to prepare fresh solutions or aliquot and store at low temperature to maintain integrity. Always verify concentration by UV-Vis absorbance or another analytical method when precision is required. Specific solubility values have not been confirmed in the source material and should be experimentally verified by the end user.
Synthetic Applications and Cross-Coupling Reactions
The C-3 iodo group of Methyl 3-iodo-1H-indole-6-carboxylate makes it an excellent electrophilic partner in palladium-catalyzed cross-coupling reactions, including Suzuki-Miyaura (with boronic acids/esters), Sonogashira (with terminal alkynes), Negishi (with organozinc reagents), and Heck reactions. These transformations allow the introduction of diverse carbon-based substituents at C-3 of the indole ring, generating a library of 3-substituted indole-6-carboxylate derivatives relevant to drug discovery programs.
The methyl ester at C-6 can be further manipulated: saponification to the carboxylic acid, reduction to the corresponding alcohol, conversion to amides, or use as a directing group in C-H functionalization. The free NH can be protected (e.g., with Boc, Ts, or PMB groups) prior to reaction sequences requiring harsh conditions or when N-selectivity must be controlled. This bifunctional design makes the compound a versatile scaffold for constructing complex heterocyclic architectures in medicinal chemistry and materials research.
Frequently asked questions
What cross-coupling reactions are compatible with Methyl 3-iodo-1H-indole-6-carboxylate?
The C-3 iodo substituent is well-suited for palladium-catalyzed Suzuki-Miyaura, Sonogashira, Negishi, and Heck reactions, enabling introduction of aryl, heteroaryl, alkynyl, and alkenyl groups at C-3. Copper-mediated coupling reactions may also be applicable. Reaction conditions should be optimized for each specific transformation.
How should Methyl 3-iodo-1H-indole-6-carboxylate be stored to maintain stability?
Store the compound in a cool, dry, and dark environment, preferably under an inert atmosphere (nitrogen or argon) after opening to prevent moisture absorption and oxidative degradation. Avoid exposure to strong oxidizers or bases. Always check for signs of decomposition before use.
Can the methyl ester group in this compound be selectively modified?
Yes. The methyl ester at C-6 can be selectively transformed through standard organic chemistry procedures: hydrolysis to the carboxylic acid, reduction to a hydroxymethyl group, or aminolysis to form amides. These transformations can be conducted while leaving the C-3 iodo group intact, provided mild and selective conditions are chosen.
What solvents are recommended for dissolving this compound?
DMSO, DMF, and THF are recommended as primary solvents based on the compound's structural features. Dichloromethane and ethyl acetate may also be suitable. Aqueous solubility is expected to be low. Users should experimentally verify solubility for their specific application, as no confirmed solubility data are provided in the current source material.
References
- General reference: March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 7th Edition. Michael B. Smith. Wiley, 2013.
- General reference: Comprehensive Organic Transformations: A Guide to Functional Group Preparations, 3rd Edition. Richard C. Larock. Wiley-VCH, 2018.
- Aladdin Scientific product listing: Methyl 3-iodo-1H-indole-6-carboxylate, SKU M710164.
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