Physical and Chemical Properties

2-Chloro-6-iodotoluene (C113587) is an ortho-disubstituted aromatic compound with a methyl group, a chlorine atom, and an iodine atom positioned on a benzene ring. Its molecular formula is C₇H₆ClI and its molecular weight is approximately 252.48 g/mol. The compound is typically a pale yellow to light amber liquid or low-melting solid at ambient temperature.

The two halogen substituents exhibit markedly different reactivity: the C–I bond undergoes oxidative addition to palladium(0) and nickel(0) catalysts at significantly lower activation energies than the C–Cl bond. This electronic and kinetic differentiation is the foundation for selective sequential functionalization strategies. The methyl group at the 1-position exerts a mild electron-donating inductive effect, slightly modulating the electrophilicity of the ring toward nucleophilic organometallic partners.

Note: Exact melting/boiling point data should be confirmed from the supplier's certificate of analysis or a validated physicochemical database before use.

Synthetic Applications and Reaction Protocols

The orthogonal reactivity of the C–I and C–Cl bonds in 2-Chloro-6-iodotoluene enables powerful sequential cross-coupling strategies. Researchers routinely exploit the C–I bond in the first synthetic step using mild Pd(0) or Pd(II) pre-catalysts, leaving the C–Cl bond intact for a subsequent, higher-temperature or more forcing coupling step or for nucleophilic aromatic substitution.

Representative Reaction Classes

• Suzuki–Miyaura Coupling: The C–I bond reacts selectively with arylboronic acids under standard Pd catalysis (e.g., Pd(PPh₃)₄ or Pd(dppf)Cl₂, K₂CO₃, DMF or toluene, 80–100 °C) to give biaryl products while the C–Cl bond remains untouched.
• Sonogashira Coupling: Terminal alkynes couple selectively at the C–I position using Pd/Cu co-catalysis under mild conditions, affording aryl alkynes useful in natural product synthesis and materials science.
• Negishi and Kumada Couplings: Organozinc and organomagnesium nucleophiles show high selectivity for the C–I bond, enabling construction of complex biaryl and alkylarene frameworks.
• Directed Lithiation: The combined directing effects of the methyl and halogen substituents can be leveraged for directed ortho-metalation (DoM) prior to electrophilic trapping, introducing additional functionality regioselectively.
• Sequential Difunctionalization: Because the C–Cl bond remains viable after C–I functionalization, sequential coupling produces non-symmetrical teraryls or heterocyclic architectures of value in medicinal chemistry and agrochemical research.

Guideline: Always optimize catalyst loading, base, and solvent for your specific substrate combination. Reaction conditions cited here are general starting points derived from well-established cross-coupling methodology; specific optimisation data should be verified in primary literature.

Safe Handling, Storage, and Waste Disposal

As a halogenated aromatic compound, 2-Chloro-6-iodotoluene should be handled with appropriate precautions. Although compound-specific GHS hazard data are not reproduced here, general best-practice guidelines for aryl halides apply:

• Personal Protective Equipment (PPE): Wear chemical-resistant gloves (nitrile or neoprene), a laboratory coat, and safety glasses. Use a fume hood for all weighing and transfer operations.
• Inhalation: Avoid breathing vapours or aerosols. Ensure adequate local exhaust ventilation.
• Skin and Eye Contact: In case of skin contact, wash thoroughly with soap and water. For eye contact, irrigate with copious water for at least 15 minutes and seek medical advice.
• Storage: Store in a tightly sealed container in a cool (below 25 °C), dark, and dry location. Keep away from strong bases, oxidising agents, and incompatible metals. Refrigerated storage may be appropriate for long-term stability.
• Waste Disposal: Dispose of according to local, national, and institutional regulations for halogenated organic waste. Do not pour down the drain. Incineration in a permitted facility is the recommended treatment.

Always consult the current Safety Data Sheet (SDS) supplied by Aladdin Scientific before use. Hazard classifications and first-aid measures specific to this material are detailed in the SDS.

Quality, Purity, and Analytical Characterisation

For successful application in sensitive cross-coupling reactions, reagent purity is critical. Aladdin Scientific's C113587 is supplied with a certificate of analysis (CoA) documenting lot-specific purity data. Researchers should verify purity by one or more of the following analytical techniques before use in demanding synthetic sequences:

• GC or HPLC: Chromatographic purity assessment is the most direct method. A purity of ≥97% (GC) is typically required for reliable cross-coupling yields.
• ¹H and ¹³C NMR Spectroscopy: Confirms the regiochemical identity of the chloro/iodo substitution pattern and the absence of significant impurities. The characteristic aromatic proton patterns and methyl singlet provide unambiguous structural confirmation.
• Mass Spectrometry (EI-MS or ESI-MS): The characteristic isotope pattern of the Cl and I atoms (and their molecular ion cluster) confirms compound identity.
• Elemental Analysis: Provides orthogonal confirmation of elemental composition when high-confidence identity verification is required.

Proper characterisation data should be archived with your laboratory notebook records for reproducibility and regulatory compliance. Contact Aladdin Scientific technical support for lot-specific CoA documentation.

Regulatory Considerations and Transport Information

2-Chloro-6-iodotoluene is subject to the regulations governing transport of hazardous chemicals. While this compound is not classified as a controlled substance under common pharmaceutical precursor regulations, researchers and procurement teams should be aware of the following general considerations:

• IATA/IMDG Classification: Halogenated aromatic compounds may be classified as Class 6.1 (Toxic Substances) or Class 9 (Miscellaneous Dangerous Goods) depending on specific hazard data. Confirm the applicable UN number and packing group with the current SDS before shipping.
• RoHS / REACH (EU): As a substance containing halogens, suppliers are required to verify REACH registration status and SVHC (Substance of Very High Concern) listing. Consult the SDS for current EU compliance information.
• Institutional Requirements: Many institutions require chemical inventory registration and risk assessment documentation before procurement of halogenated organic reagents. Engage your Environmental Health & Safety (EHS) office as appropriate.
• Export Controls: Check applicable export control regulations in your jurisdiction before international shipment.

Disclaimer: Regulatory classifications change over time. Always verify current status with the applicable regulatory authority and Aladdin Scientific's documentation before ordering or shipping.