5-Bromo-2,3-diiodopyridine: Handling & Application Protocol

5-Bromo-2,3-diiodopyridine is a polyhalogenated pyridine building block bearing three distinct halogen substituents that enable highly selective sequential cross-coupling and functionalization reactions in medicinal and synthetic chemistry.

CAS Number

1261365-63-2 — verify against current registry

Molecular Formula

C₅H₂BrI₂N

Molecular Weight

Approximately 404.78 g/mol (needs verification)

SKU

B180773

Key Reactivity

C–I bonds react preferentially under Pd/Ni-catalyzed coupling conditions; C–Br bond provides orthogonal handle for subsequent functionalization

Storage Recommendation

Store in a cool, dry, well-ventilated area away from light; check SDS for specific conditions

Purity

See certificate of analysis supplied with each lot (B180773)

Overview and Chemical Properties

5-Bromo-2,3-diiodopyridine (SKU B180773) is a trihalogenated pyridine in which iodine atoms occupy the 2- and 3-positions and a bromine atom occupies the 5-position of the pyridine ring. The differential reactivity of the three carbon–halogen bonds makes this compound a versatile orthogonal building block: carbon–iodine bonds are significantly more reactive than carbon–bromine bonds under most transition-metal-catalyzed conditions, permitting chemists to perform selective, sequential cross-coupling reactions at distinct ring positions.

The compound is a solid at room temperature. Its electron-deficient pyridine ring, combined with the inductive effects of three halogen substituents, makes it susceptible to nucleophilic aromatic substitution at appropriate positions and a useful scaffold for the preparation of multi-substituted heteroaromatic targets encountered in pharmaceutical and agrochemical research.

Safety and Handling

Personal Protective Equipment (PPE): Always wear appropriate PPE when handling 5-Bromo-2,3-diiodopyridine, including nitrile gloves, a laboratory coat, and safety glasses or a face shield. Handle in a well-ventilated fume hood to minimize inhalation of dust or vapors.

Storage: Store the reagent in a tightly sealed container in a cool, dry location away from direct light, heat sources, and incompatible materials such as strong oxidizers and bases. Consult the Safety Data Sheet (SDS) supplied by Aladdin Scientific for specific hazard classifications, first-aid measures, and disposal regulations applicable in your jurisdiction.

Disposal: Dispose of waste material in accordance with local, regional, and national regulations governing halogenated organic compounds. Do not dispose of down the drain.

Note: Specific GHS hazard classifications and pictograms for B180773 should be confirmed against the current Aladdin SDS prior to use.

Protocol: Selective Suzuki–Miyaura Cross-Coupling at the C–I Bond

The following procedure outlines a general approach for chemoselective mono-coupling at one of the C–I positions of 5-Bromo-2,3-diiodopyridine. Specific conditions (solvent, base, temperature, catalyst loading) must be optimized for each individual transformation. This protocol is intended as a starting framework; consult primary literature for validated conditions relevant to your target substrate.

1. Materials: 5-Bromo-2,3-diiodopyridine (B180773, 1.0 equiv), arylboronic acid or ester (1.0–1.2 equiv), Pd catalyst (e.g., Pd(PPh₃)₄ or Pd(dppf)Cl₂, 2–5 mol%), inorganic base (e.g., K₂CO₃ or Cs₂CO₃, 2–3 equiv), solvent (e.g., DMF/H₂O, dioxane/H₂O, or THF/H₂O mixtures), inert atmosphere (N₂ or Ar).
2. Setup: Charge a dry Schlenk flask or sealed vial with the substrate, boronic coupling partner, and Pd catalyst under inert gas. Add degassed solvent and aqueous base solution.
3. Reaction: Stir the reaction mixture at 60–100 °C (temperature to be optimized) for 4–24 h under inert atmosphere. Monitor by TLC or LC-MS.
4. Workup: Cool to room temperature. Dilute with ethyl acetate, wash with saturated aqueous NH₄Cl and brine, dry over MgSO₄, filter, and concentrate in vacuo.
5. Purification: Purify the crude product by silica gel column chromatography (hexane/EtOAc gradient) or recrystallization as appropriate.

Important: The chemoselectivity between the two C–I bonds at C-2 and C-3 will depend on steric and electronic factors as well as the specific catalytic system used. Optimization is strongly recommended. C–Br bond is expected to remain intact under mild coupling conditions.

Quality Control and Verification

Upon receipt of 5-Bromo-2,3-diiodopyridine (B180773), inspect the material and review the Certificate of Analysis (CoA) provided by Aladdin Scientific. The CoA documents lot-specific purity data typically determined by techniques such as HPLC or GC, along with NMR characterization confirming structural identity.

Recommended identity checks before use:

• ¹H NMR: Confirm the number and chemical shifts of aromatic protons consistent with a 2,3,5-trisubstituted pyridine. Two proton signals are expected for the pyridine ring (H-4 and H-6 positions).
• ¹³C NMR or MS: Confirm the molecular ion consistent with C₅H₂BrI₂N (exact mass needs verification against authoritative source).
• Melting point: Compare with the reported value on the CoA or in the literature (specific value not confirmed; flag for review).

If purity is below the specification required for your application, consider additional purification by recrystallization from a suitable solvent or contact Aladdin Scientific technical support.

Applications in Medicinal and Synthetic Chemistry

5-Bromo-2,3-diiodopyridine serves as a key intermediate in the synthesis of complex polysubstituted pyridines that appear in bioactive molecules, agrochemicals, and functional materials. Its principal utility arises from the ability to exploit the orthogonal reactivity of C–I versus C–Br bonds:

• Sequential cross-coupling: Perform an initial Suzuki–Miyaura, Negishi, Stille, or Sonogashira coupling selectively at a C–I bond, then execute a second coupling or other transformation at the remaining C–I or C–Br bond in subsequent steps.
• Metal–halogen exchange: Treatment with n-BuLi or i-PrMgCl·LiCl at low temperature can effect selective halogen–metal exchange at C–I positions, generating organolithium or organomagnesium intermediates for reaction with electrophiles.
• Directed C–H functionalization scaffolds: The nitrogen atom and halogen substituents can direct further functionalization reactions.
• Pharmaceutical building blocks: Multihalogenated pyridines are frequently employed in fragment-based drug discovery and in the construction of kinase inhibitor scaffolds and other heterocyclic pharmacophores.

Specific literature examples employing B180773 directly should be verified; researchers are encouraged to conduct a current SciFinder or Reaxys search for the most up-to-date synthetic applications.

Frequently asked questions

What is the preferred order of halogen reactivity in cross-coupling reactions with 5-Bromo-2,3-diiodopyridine?

Under standard palladium- or nickel-catalyzed cross-coupling conditions, C–I bonds are considerably more reactive than C–Br bonds due to the weaker C–I bond and easier oxidative addition into Pd(0). This allows the two iodo substituents at C-2 and C-3 to be coupled selectively before engaging the C–Br bond at C-5 under mild conditions. Selectivity between the two C–I positions depends on steric and electronic environment and must be empirically optimized.

How should 5-Bromo-2,3-diiodopyridine (B180773) be stored to maintain stability?

The compound should be stored in a tightly sealed container in a cool, dry, and well-ventilated area away from direct light and heat. Consult the Aladdin Scientific SDS and the Certificate of Analysis for any lot-specific storage temperature recommendations. Moisture and prolonged exposure to light can potentially promote degradation of halogenated heterocycles, so desiccant storage may be advisable.

Can 5-Bromo-2,3-diiodopyridine undergo Sonogashira coupling, and at which position?

Yes, Sonogashira coupling (Pd/Cu-catalyzed coupling with terminal alkynes) is feasible at the C–I positions under standard conditions. Because C–I bonds are more reactive than C–Br bonds under Sonogashira conditions, selective alkynylation at C-2 or C-3 is expected before the C-5 bromine is engaged. Regioselectivity between C-2 and C-3 iodo groups requires empirical investigation and optimization of catalyst, ligand, and temperature.

Where can I find the Certificate of Analysis and Safety Data Sheet for B180773?

The Certificate of Analysis (CoA) and Safety Data Sheet (SDS) for 5-Bromo-2,3-diiodopyridine (B180773) are available through the Aladdin Scientific website product page for B180773, or by contacting Aladdin Scientific customer service directly. Always consult the lot-specific CoA to confirm purity and identity data for your batch.

References

1. General reference: Negishi, E. (Ed.) Handbook of Organopalladium Chemistry for Organic Synthesis. Wiley-Interscience, 2002. (For cross-coupling methodology with halopyridines.)
2. Littke, A. F.; Fu, G. C. Palladium-Catalyzed Coupling Reactions of Aryl Chlorides. Angew. Chem. Int. Ed. 2002, 41, 4176–4211. (Background on Pd-catalyzed cross-coupling selectivity.) doi:10.1002/1521-3773(20021115)41:22<4176::AID-ANIE4176>3.0.CO;2-U
3. Aladdin Scientific Certificate of Analysis, SKU B180773, 5-Bromo-2,3-diiodopyridine (lot-specific document; consult Aladdin Scientific directly).

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