2,5-Dibromopyridine
[CAS 624-28-2]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyridine compound >> Bromopyridine
• Name: 2,5-Dibromopyridine
• Molecular Formula: C₅H₃Br₂N
• Molecular Weight: 236.89
• CAS Registry Number: 624-28-2
• EC Number: 210-839-6
• SMILES: C1=CC(=NC=C1Br)Br

Properties

• Density: 2.1$+/-$0.1 g/cm³ Calc.^*
• Melting point: 92 - 95 $degree$C (Expl.)
• Boiling point: 235.7$+/-$20.0 $degree$C 760 mmHg (Calc.)^*, 249 $degree$C (Expl.)
• Flash point: 96.4$+/-$21.8 $degree$C (Calc.)^*
• Solubility: water: insoluble (Expl.)
• Index of refraction: 1.607 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2	H319
Acute toxicity	Acute Tox.	4	H312
Acute toxicity	Acute Tox.	4	H332
Acute toxicity	Acute Tox.	4	H302
Eye irritation	Eye Irrit.	2A	H319

Discovery and Applications

2,5-Dibromopyridine is a halogenated aromatic heterocycle derived from pyridine, in which two hydrogen atoms on the pyridine ring are replaced by bromine atoms at the 2- and 5-positions. Pyridine is a six-membered aromatic ring containing one nitrogen atom, and it is inherently electron-deficient compared with benzene due to the electronegativity of the ring nitrogen.

The presence of bromine substituents significantly alters both the electronic and chemical properties of the pyridine ring. Bromine is strongly polarizable and exerts a net electron-withdrawing inductive effect, which further decreases electron density in the heteroaromatic system. This makes 2,5-dibromopyridine more reactive toward nucleophilic aromatic substitution than unsubstituted pyridine derivatives, especially at positions activated by the ring nitrogen.

The 2-position in pyridine is adjacent to the ring nitrogen and is therefore electronically activated toward nucleophilic attack in certain substitution reactions due to stabilization of anionic intermediates by the heteroatom. The 5-position, located on the carbon framework further from the nitrogen, is also influenced by the overall electron-withdrawing nature of the ring and the substituents, though typically to a lesser extent than the 2-position in terms of mechanistic reactivity.

The carbon–bromine bonds in 2,5-dibromopyridine are key reactive sites. These bonds can participate in a wide range of transition-metal-catalyzed cross-coupling reactions, such as Suzuki, Heck, and Sonogashira couplings. This makes the compound a valuable bifunctional building block in synthetic organic chemistry, where sequential or selective functionalization of the two bromine sites can be used to construct more complex heterocyclic or aromatic systems.

Regioselective differentiation of the two bromine substituents is often possible due to their differing electronic environments. The bromine at the 2-position, being adjacent to the nitrogen atom, is typically more activated toward oxidative addition in palladium-catalyzed processes compared with the 5-position bromine. This allows chemists to perform stepwise functionalization strategies.

From a structural perspective, the pyridine ring remains planar and aromatic, with delocalized π-electrons across the ring system. The nitrogen atom contributes to the ring’s electron deficiency and provides a site for coordination to metals or protonation under acidic conditions, forming pyridinium species. This coordination ability is important in catalysis and in the formation of metal–organic complexes.

The molecule’s physicochemical properties are influenced by both halogen substitution and aromatic heterocycle character. It is relatively hydrophobic compared with unsubstituted pyridine due to the presence of two bromine atoms, which increase molecular weight and polarizability. However, the ring nitrogen maintains some degree of polarity and basicity, although the electron-withdrawing bromines reduce its basicity compared with pyridine itself.

2,5-Dibromopyridine is commonly used as an intermediate in the synthesis of pharmaceuticals, agrochemicals, and functional materials. Its bifunctional halogenation pattern makes it especially useful for constructing asymmetrically substituted pyridine derivatives, which are important scaffolds in medicinal chemistry.

In coordination chemistry, substituted pyridines can act as ligands through the nitrogen atom, although steric and electronic effects from the bromine substituents may influence binding strength and geometry in metal complexes.

Overall, 2,5-dibromopyridine is a halogenated pyridine derivative characterized by two reactive bromine substituents and an electron-deficient aromatic heterocycle. Its significance lies in its versatility as a synthetic intermediate, particularly in cross-coupling chemistry and the stepwise construction of complex nitrogen-containing aromatic compounds.

References

2025. Organic Electrode Materials for Lithium/Sodium/Potassium-Ion Batteries: Synthesis, Characterizations, Functional Mechanisms, and Performance Validation. Electrochemical Energy Reviews.
DOI: 10.1007/s41918-025-00250-3