4-Bromo-2-iodophenol: Properties, Handling & Synthetic Uses

4-Bromo-2-iodophenol is a difunctionalized halogenated phenol that serves as a versatile orthogonal building block in palladium- and copper-catalyzed cross-coupling chemistry, enabling the selective sequential functionalization of two distinct carbon–halogen bonds.

CAS Number

186268-06-4

Molecular Formula

C₆H₄BrIO

Molecular Weight

298.91 g/mol

Appearance

White to off-white crystalline solid

Key Functional Groups

Phenol (–OH), aryl bromide (C–Br), aryl iodide (C–I)

Storage Condition

Store in a cool, dry place away from light; seal under inert atmosphere if possible

SKU

B152695

Chemical Identity and Physical Properties

4-Bromo-2-iodophenol (CAS 186268-06-4, MW 298.91 g/mol, molecular formula C₆H₄BrIO) is an aromatic compound bearing three distinct functional groups on the benzene ring: a hydroxyl group at position 1, an iodo substituent at position 2 (ortho), and a bromo substituent at position 4 (para). This precise substitution pattern gives each carbon–halogen bond a different reactivity profile under transition-metal catalysis.

The compound typically presents as a white to off-white crystalline solid at room temperature. Its relatively high molecular weight compared to monohalogenated phenols reflects the incorporation of both heavy halogens. The phenolic –OH group renders the molecule weakly acidic and capable of hydrogen-bond donation, influencing its solubility: it is generally soluble in common organic solvents such as dichloromethane, tetrahydrofuran, ethyl acetate, and dimethylformamide, but sparingly soluble in water.

Synthetic Applications and Reactivity

The principal value of 4-Bromo-2-iodophenol in synthetic chemistry lies in the orthogonal reactivity of its two carbon–halogen bonds. The aryl C–I bond is considerably more reactive toward oxidative addition into low-valent palladium(0) complexes than the aryl C–Br bond. This reactivity difference allows chemists to functionalize the iodo position selectively in the first step, then engage the bromo position in a subsequent transformation under modified conditions—or vice versa using copper catalysis—without the need for protecting-group manipulations.

Palladium-catalyzed cross-coupling: The C–I bond participates preferentially in Suzuki–Miyaura (with arylboronic acids), Sonogashira (with terminal alkynes), Heck, Negishi, and Stille coupling reactions under mild conditions. After selective coupling at the iodo site, the remaining C–Br bond can be engaged in a second cross-coupling cycle.

Copper-catalyzed reactions: The C–Br bond is amenable to Ullmann-type ether or amine formation and Chan–Lam coupling. When combined with the free phenol, intramolecular cyclization strategies become available, enabling efficient synthesis of benzofuran scaffolds and related heterocycles.

Phenol as a directing or coupling handle: The free –OH group can be protected (e.g., as a TBS ether, methyl ether, or triflate), converted to a leaving group for additional cross-coupling, or exploited as an O-nucleophile in intramolecular cyclizations, significantly expanding the synthetic utility of this building block.

Safety, Handling and Storage Guidelines

Hazard profile: As a halogenated aromatic phenol, 4-Bromo-2-iodophenol should be treated as an irritant capable of causing skin, eye, and respiratory tract irritation. Phenolic compounds as a class may be corrosive at higher concentrations. Consult the material Safety Data Sheet (SDS) supplied with Aladdin Scientific product B152695 for the definitive GHS hazard classification, pictograms, and first-aid measures before use.

Personal protective equipment (PPE): Wear appropriate chemical-resistant gloves (nitrile or neoprene recommended), safety goggles or a face shield, and a laboratory coat when handling this compound. Work in a well-ventilated area or under a fume hood to minimize inhalation of dust or vapors.

Storage: Store the reagent in a tightly sealed container in a cool (2–8 °C recommended for long-term stability), dry location away from direct light and moisture. Exposure to air and humidity over time may lead to discoloration or degradation. For extended storage, maintaining an inert-gas (nitrogen or argon) atmosphere above the sample is advisable.

Waste disposal: Dispose of waste containing halogenated aromatic compounds in accordance with local, regional, and national regulations for halogenated organic waste. Do not pour down the drain.

Quality, Purity and Analytical Considerations

For reproducible synthetic results, the purity of 4-Bromo-2-iodophenol is critical. Impurities such as residual 4-bromophenol, 2-iodophenol, or dihalogenated byproducts can complicate selectivity in cross-coupling sequences and reduce overall yields. Aladdin Scientific's B152695 is supplied with a specified purity; refer to the Certificate of Analysis (CoA) delivered with the batch for the exact assay value and analytical data.

Recommended analytical methods:

• ¹H NMR spectroscopy: The aromatic proton signals and the phenolic –OH resonance provide a rapid assessment of compound identity and purity in deuterated DMSO or CDCl₃.
• GC or HPLC: Quantitative purity determination using a reverse-phase C18 column (HPLC) or a non-polar capillary column (GC) with UV or FID detection, respectively.
• Melting point: A sharp melting point consistent with literature values confirms crystalline purity; significant depression or broadening suggests contamination.
• Mass spectrometry: The characteristic isotope pattern arising from the combined presence of ⁷⁹Br/⁸¹Br and ¹²⁷I provides an unambiguous molecular ion signature in ESI-MS or EI-MS.

Frequently asked questions

Why is 4-Bromo-2-iodophenol useful as an orthogonal cross-coupling building block?

The compound contains two chemically distinct aryl halide bonds: a C–I bond, which undergoes oxidative addition into Pd(0) much faster than the C–Br bond, and a C–Br bond that remains available for a second, separate functionalization step. This reactivity difference allows synthetic chemists to install two different groups sequentially and selectively without protecting-group chemistry.

How should 4-Bromo-2-iodophenol be stored to maintain its quality over time?

Store the compound in a tightly sealed container under cool (2–8 °C), dry, and light-protected conditions. For long-term storage, blanketing the headspace with an inert gas such as nitrogen or argon helps prevent oxidation and moisture uptake that can cause discoloration or gradual decomposition.

What safety precautions are required when handling 4-Bromo-2-iodophenol in the laboratory?

Treat the compound as an irritant. Always wear nitrile or neoprene gloves, safety goggles, and a laboratory coat. Handle it inside a fume hood to avoid inhaling dust or vapors. Consult the SDS for product B152695 before use, and dispose of all waste according to local regulations for halogenated organic waste.

Which coupling reactions are most commonly performed using 4-Bromo-2-iodophenol?

The aryl iodide functionality is most commonly used in Suzuki–Miyaura coupling with arylboronic acids, Sonogashira coupling with terminal alkynes, and Heck reactions with alkenes under palladium catalysis. The aryl bromide can subsequently engage in a second palladium-catalyzed coupling or copper-mediated Ullmann-type reactions, and the phenolic –OH enables intramolecular cyclizations to form oxygen-containing heterocycles such as benzofurans.

References

1. Aladdin Scientific product page and Certificate of Analysis for 4-Bromo-2-iodophenol, SKU B152695.
2. Negishi, E. (Ed.) Handbook of Organopalladium Chemistry for Organic Synthesis. Wiley-Interscience, 2002. General reference for palladium-catalyzed cross-coupling selectivity with aryl iodides vs. aryl bromides.
3. Johansson Seechurn, C. C. C.; Kitching, M. O.; Colacot, T. J.; Snieckus, V. Palladium-Catalyzed Cross-Coupling: A Historical Contextual Perspective to the 2010 Nobel Prize. Angew. Chem. Int. Ed. 2012, 51, 5062–5085. doi:10.1002/anie.201107017

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