4-Bromo-1H-imidazole
[CAS 2302-25-2]

Identification

• Classification: Organic raw materials >> Heterocyclic compound >> Imidazoles
• Name: 4-Bromo-1H-imidazole
• Synonyms: 5-bromo-1H-imidazole
• Molecular Formula: C₃H₃BrN₂
• Molecular Weight: 146.97
• CAS Registry Number: 2302-25-2
• EC Number: 627-452-7
• SMILES: C1=C(NC=N1)Br

Properties

• Density: 1.9±0.1 g/cm³ Calc.^*
• Melting point: 131 - 135 °C (Expl.)
• Boiling point: 324.7±15.0 °C 760 mmHg (Calc.)^*
• Flash point: 150.2±20.4 °C (Calc.)^*
• Index of refraction: 1.602 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS06;GHS07 Danger
• Risk Statements: H301-H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P270-P271-P280-P301+P316-P302+P352-P304+P340-P305+P351+P338-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	3	H301
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2A	H319
Acute toxicity	Acute Tox.	3	H311
Acute toxicity	Acute Tox.	3	H331

• Transport Information: UN 2811

chemBlink Chemical Story

4-Bromo-1H-imidazole, CAS 2302-25-2, is a brominated five-membered nitrogen heterocycle used primarily as a building block in organic and medicinal chemistry. Its molecular formula is C₃H₃BrN₂ and its molecular weight is 146.97. The molecule consists of an imidazole ring bearing bromine at the 4-position. Although structurally very small, it combines one of medicinal chemistry's most important heterocycles with a carbon-bromine bond that can be used as a precise point for further molecular construction. :contentReference[oaicite:0]{index=0}

Imidazole is a five-membered aromatic ring containing two nitrogen atoms. The two nitrogens are chemically different: one has pyridine-like character and can act as a hydrogen-bond acceptor, while the other is pyrrole-like and contributes its electron pair to the aromatic system. Because of this arrangement, imidazole can participate in proton transfer, hydrogen bonding, coordination to metals, and numerous other interactions.

The importance of imidazole extends far beyond synthetic chemistry. The amino acid histidine contains an imidazole side chain, and this group plays crucial roles in protein structure and enzyme catalysis. Histidine residues can accept or donate protons near physiological pH and frequently appear in enzyme active sites. The heme protein histidine coordination found in hemoglobin and many enzymes provides another illustration of the ring's ability to interact with metal centers.

Imidazole rings also occur in numerous pharmaceuticals, agrochemicals, catalysts, ligands, and functional materials. For medicinal chemists, the ring offers a compact combination of aromaticity, polarity, hydrogen-bonding capability, and relatively small size. Substituting different groups around the ring provides a way to tune these properties and explore how molecular structure affects biological recognition.

4-Bromo-1H-imidazole adds a particularly useful synthetic feature to this familiar scaffold. The carbon-bromine bond at the 4-position can serve as a temporary synthetic handle. Under transition-metal-catalyzed conditions, bromine can be replaced by carbon-containing, nitrogen-containing, or other molecular fragments. In this way, the imidazole ring can be retained while its 4-position is systematically diversified.

Suzuki-Miyaura cross-coupling is one of the most important examples. In 2007, Bellina and coworkers reported an efficient method for preparing 4(5)-aryl-1H-imidazoles by palladium-catalyzed Suzuki-Miyaura coupling of commercially available 4(5)-bromo-1H-imidazole with arylboronic acids. An important feature of the method was that the imidazole nitrogen did not necessarily require a permanent protecting group. The reaction could directly provide aryl-substituted imidazoles from the unprotected heterocycle.

This capability is significant because unprotected nitrogen heterocycles can be challenging participants in transition-metal catalysis. Nitrogen atoms may coordinate to the metal catalyst and interfere with the catalytic cycle. Earlier synthetic approaches therefore often protected the imidazole nitrogen before coupling and removed the protecting group later. Developing conditions that tolerate the free N-H can reduce the number of synthetic operations.

Later studies expanded this concept. In 2014, researchers reported Suzuki-Miyaura cross-coupling of unprotected bromoimidazoles with a broad range of aryl- and heteroarylboronic acids. Palladium-catalyzed amination of unprotected bromoimidazoles was also developed, demonstrating that the brominated position can be used not only to create carbon-carbon bonds but also carbon-nitrogen bonds. :contentReference[oaicite:1]{index=1}

These transformations turn 4-bromoimidazole into a common branching point for molecular libraries. A medicinal chemist can begin with the same small heterocycle and replace bromine with phenyl, pyridyl, another heteroaryl group, an amino substituent, or numerous other fragments. Each new compound preserves the imidazole core while changing one defined region of molecular space.

This is the foundation of structure-activity relationship research. Rather than asking whether "imidazole" itself is biologically active, researchers ask how changing the substituent attached to a particular position affects potency, selectivity, solubility, metabolic behavior, and other properties. A brominated intermediate makes such systematic variation much easier.

The chemistry of imidazole has an additional subtlety: the 4- and 5-positions of an unsubstituted 1H-imidazole can be related through proton tautomerism. The proton can shift between the two ring nitrogens, changing how the carbon positions are numbered in different tautomeric representations. Consequently, older literature and commercial descriptions sometimes use the notation 4(5)-bromoimidazole or refer to 4- and 5-substitution together. This does not mean that two unrelated compounds are being discussed; it reflects the tautomeric nature of the free N-H imidazole system.

This tautomerism is one reason imidazole chemistry is richer than the simple five-membered structural formula suggests. Once the nitrogen is substituted, the symmetry relationship is broken and individual carbon positions become more straightforward to distinguish. Synthetic chemists can exploit this difference when designing regioselective routes to more highly substituted imidazoles.

4-Bromo-1H-imidazole therefore represents a particularly useful type of research chemical: a biologically familiar scaffold equipped with a replaceable atom. The imidazole ring supplies the hydrogen-bonding and electronic properties that make this heterocycle valuable, while bromine marks a position where chemical diversity can be introduced.

In modern medicinal chemistry, that combination is powerful. One small reagent can become the parent of dozens or hundreds of analogs. The bromine is temporary, but the position it identifies is permanent in the synthetic plan. It tells the chemist exactly where the next molecular idea can be attached.

References

1. PubChem. 4-Bromo-1H-imidazole, CID 96125. CAS 2302-25-2.
https://pubchem.ncbi.nlm.nih.gov/compound/4-Bromo-1H-imidazole

2. Bellina, F.; Cauteruccio, S.; Rossi, R. (2007). "Efficient and Practical Synthesis of 4(5)-Aryl-1H-imidazoles via Palladium-Catalyzed Suzuki-Miyaura Cross-Coupling." Journal of Organic Chemistry.
https://doi.org/10.1021/jo701496p

3. Tan, J. et al. (2014). "Suzuki-Miyaura Cross-Coupling Reactions of Unprotected Bromoimidazoles." Journal of Organic Chemistry.
https://doi.org/10.1021/jo501326r

4. Su, M. et al. (2014). "Palladium-Catalyzed Amination of Unprotected Five-Membered Heterocyclic Bromides." Organic Letters.

5. Iddon, B. (1986). Synthetic chemistry of mono-, di-, and trisubstituted imidazoles through functional-group interconversion of brominated imidazoles. Tetrahedron.