What Is 3-Chloro-2-iodoaniline and Why Is It Useful?

3-Chloro-2-iodoaniline (CAS C194678) is an ortho-substituted halogenated aniline in which an iodo group occupies the 2-position and a chloro group occupies the 3-position relative to the primary amine. This substitution pattern is synthetically significant for three reasons.

First, the aryl iodide bond is highly reactive toward oxidative addition into palladium(0) catalysts, enabling selective Suzuki–Miyaura, Sonogashira, Buchwald–Hartwig, and related cross-coupling reactions at the C–I position under mild conditions, while the C–Cl bond can be functionalized in a second, orthogonal step or left intact to modulate the electronics of the ring.

Second, the free amino group (–NH₂) serves both as a directing group for transition-metal-catalyzed C–H activation and as a nucleophile or handle for amide bond formation, reductive amination, and N-arylation chemistry.

Third, the combination of the electron-donating amine and two electron-withdrawing halogens creates a uniquely polarized aromatic system suitable for the construction of nitrogen-containing heterocycles such as indoles, benzimidazoles, and quinazolines via intramolecular cyclization strategies.

What Are the Key Physical and Chemical Properties?

3-Chloro-2-iodoaniline is typically obtained as a solid or low-melting solid at room temperature. Its molecular formula is C₆H₅ClIN and its molecular weight is 253.47 g/mol. The compound contains three distinct reactive sites—the amine, the aryl iodide, and the aryl chloride—each with different reactivity profiles that can be exploited sequentially in multi-step synthesis.

The aryl C–I bond dissociation energy is substantially lower than that of C–Cl, providing clear chemoselectivity: palladium catalysts preferentially oxidatively add into C–I bonds, typically at room temperature or slightly elevated temperatures, whereas C–Cl activation generally requires more forcing conditions or specialized catalyst systems. This chemoselectivity is one of the primary reasons researchers select this compound as a building block.

The amine group raises the electron density of the ring at ortho and para positions relative to –NH₂, partially counteracting the electron-withdrawing influence of the two halogens. The net electronic environment makes the ring moderately electron-rich at nitrogen-bearing positions while leaving the halogen-bearing carbons electrophilic, which is important for regioselective reactions.

Note: Specific melting point, boiling point, density, and purity specifications should be confirmed from the current Aladdin Scientific Certificate of Analysis (CoA) for lot C194678.

How Should 3-Chloro-2-iodoaniline Be Stored and Handled Safely?

Storage: Store in a tightly sealed container in a cool, dry location away from direct light and sources of heat. Prolonged exposure to air and moisture can lead to oxidation or hydrolytic degradation of the sensitive C–I bond and the free amine. Refrigerated storage (2–8 °C) is recommended for long-term stability. Always re-seal the container promptly after use.

Personal Protective Equipment (PPE): As with all aryl halide amines, standard laboratory PPE is required: chemical-resistant gloves (nitrile recommended), safety goggles, and a laboratory coat. Work in a well-ventilated fume hood to minimize inhalation of dusts or vapors.

Regulatory and Hazard Classification: Exact GHS hazard classifications, signal words, and H/P statements should be confirmed from the current Safety Data Sheet (SDS) provided by Aladdin Scientific for SKU C194678. Researchers should review the SDS before first use and follow all institutional EHS guidelines.

Waste Disposal: Dispose of waste material in accordance with local, national, and institutional regulations for halogenated organic compounds. Do not pour down the drain.

Typical Synthetic Applications and Reaction Conditions

Selective Cross-Coupling at C–I: The most common use of 3-Chloro-2-iodoaniline is as a substrate for palladium-catalyzed cross-coupling reactions that selectively functionalize the aryl iodide. For Suzuki–Miyaura coupling, typical conditions employ Pd(PPh₃)₄ or Pd(dppf)Cl₂ as catalyst, a base such as K₂CO₃ or Cs₂CO₃, and a boronic acid partner in a polar aprotic or aqueous-organic solvent system. The C–Cl bond remains largely intact under these conditions.

Sonogashira Coupling: Terminal alkynes can be coupled at the C–I position using Pd/Cu co-catalyst systems (e.g., Pd(PPh₃)₂Cl₂ / CuI) with a trialkylamine base in THF or DMF. The resulting internal alkyne product, bearing a free amine and aryl chloride, is a versatile precursor to indoles and other heterocycles via cyclization.

Buchwald–Hartwig Amination: The compound can also serve as an electrophilic partner in palladium-catalyzed C–N bond formation, where the aryl iodide undergoes amination with primary or secondary amines using BINAP- or XPhos-based catalyst systems.

Heterocycle Synthesis: The ortho-amino/aryl-iodide combination is a classical motif for the synthesis of 2-substituted benzimidazoles and indoles. After initial coupling to install a functional group at C–2 relative to the amine, intramolecular condensation or cyclization under acidic or basic conditions delivers the target heterocycle.

Note: Specific reaction yields, temperatures, and catalyst loadings cited in literature should be verified from primary references before application.

Ordering, Purity, and Quality Information

Catalog Information: 3-Chloro-2-iodoaniline is available from Aladdin Scientific under SKU C194678. Please visit the product page on aladdinsci.com or contact your regional sales representative for current pack sizes, pricing, and availability.

Purity and Specifications: Aladdin Scientific provides a Certificate of Analysis (CoA) with each lot, detailing purity (typically assessed by GC or HPLC), appearance, and identity confirmation (e.g., NMR or MS). Researchers requiring ultra-high purity for sensitive assays should request the CoA for their specific lot and confirm that the purity level meets their experimental requirements before use.

Custom Quantities: For bulk or custom quantities, please contact the Aladdin Scientific sales team directly. Lead times and pricing may vary for non-standard pack sizes.

Returns and Quality Issues: In the event of quality concerns, Aladdin Scientific's customer service team should be contacted promptly with the lot number and CoA. Please refer to the current Returns and Refunds policy available on the Aladdin Scientific website for full details.