2-Bromo-5-chlorophenol
[CAS 13659-23-9]

Identification

• Classification: Organic raw materials >> Alcohols, phenols, phenolic compounds and derivatives
• Name: 2-Bromo-5-chlorophenol
• Molecular Formula: C₆H₄BrClO
• Molecular Weight: 207.45
• CAS Registry Number: 13659-23-9
• EC Number: 603-968-8
• SMILES: C1=CC(=C(C=C1Cl)O)Br

Properties

• Density: 1.8±0.1 g/cm³ Calc.^*
• Boiling point: 222.2±20.0 °C 760 mmHg (Calc.)^*
• Flash point: 88.2±21.8 °C (Calc.)^*
• Index of refraction: 1.619 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-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.	4	H302
Specific target organ toxicity - single exposure	STOT SE	3	H335
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2A	H319

chemBlink Chemical Story

2-Bromo-5-chlorophenol, CAS 13659-23-9, is a dihalogenated phenol used primarily as a building block in organic synthesis and medicinal chemistry. Its molecular formula is C₆H₄BrClO and its molecular weight is 207.45. The molecule contains three conspicuous functional features on one aromatic ring: a phenolic hydroxyl group, bromine adjacent to that hydroxyl group, and chlorine at the 5-position. This compact combination provides several opportunities for selective chemical transformation.

The basic framework is phenol, whose hydroxyl group strongly influences the electronic properties of the aromatic ring and also provides a convenient site for derivatization. Phenolic hydroxyl groups can be converted into ethers, esters, sulfonates, and other derivatives. In a multistep synthesis, the hydroxyl group may therefore be used either as a functional group retained in the target molecule or as a connection point for attaching another molecular fragment.

Bromine provides a second and quite different synthetic handle. Aromatic carbon-bromine bonds are widely used in transition-metal-catalyzed cross-coupling chemistry. Reactions such as Suzuki-Miyaura coupling can replace the brominated position with a new carbon-containing group, while Buchwald-Hartwig and related transformations can create carbon-nitrogen or other bonds. This allows the original brominated phenol to become the starting point for much larger molecular structures.

The chlorine atom introduces another useful distinction. Although both bromine and chlorine are halogens, aryl bromides are generally more reactive than corresponding aryl chlorides in many palladium-catalyzed coupling reactions. With appropriate catalyst and reaction conditions, chemists can therefore sometimes react at the brominated position while leaving the chlorine substituent intact. The remaining chlorine may simply be desired in the final molecule or may provide another opportunity for later chemistry.

This difference illustrates one of the most important concepts in multistep organic synthesis: chemoselectivity. A molecule containing several potentially reactive groups is much more useful when chemists can choose which one to modify first. Instead of treating 2-bromo-5-chlorophenol as a ring carrying two interchangeable halogens, the synthetic chemist can regard bromine and chlorine as connection points with different levels of accessibility.

The location of bromine next to the hydroxyl group can also be valuable. Ortho-substituted phenols are useful precursors to many oxygen-containing heterocycles because the neighboring substituents can eventually become part of a newly formed ring. Benzofurans, benzoxazoles, benzoxazines, and related fused aromatic systems are frequently constructed from appropriately functionalized ortho-substituted phenols, although the exact transformation depends on the other reagents and substituents involved.

Published synthetic chemistry shows 2-bromo-5-chlorophenol being converted into more elaborate aromatic intermediates. The phenolic oxygen can first be alkylated, for example, while the aryl bromide remains available for subsequent carbon-carbon bond formation. Alternatively, the brominated position can be transformed first and the hydroxyl functionality preserved or protected. Such sequences demonstrate why apparently simple halophenols are routinely stocked as research building blocks.

This strategy is especially important in medicinal chemistry. Researchers often need to prepare a series of closely related molecules in which only one portion of the structure changes. Starting with a compound containing bromine, chlorine, and hydroxyl functionality allows several analogs to be prepared from a common intermediate. One branch of a synthesis may modify the brominated position, another may change the phenolic oxygen substituent, and a third may preserve chlorine while varying other parts of the molecule.

Halogen atoms themselves can also influence the properties of final biologically active molecules. Chlorine and bromine can change molecular size, polarizability, lipophilicity, conformation, and interactions with proteins. In some molecular environments, a halogen can participate in directional noncovalent interactions commonly described as halogen bonding. None of these effects means that 2-bromo-5-chlorophenol itself has a particular pharmacological activity; rather, they help explain why halogenated aromatic fragments are frequently explored during molecular optimization.

From a manufacturing perspective, halogenated phenols are also useful because the aromatic ring already contains much of the substitution pattern required for later synthesis. Installing substituents at precisely selected positions on an aromatic ring can require several steps. Beginning with a commercially available intermediate such as 2-bromo-5-chlorophenol can therefore shorten a synthetic route and reduce the need to construct the substitution pattern from a simpler phenol.

The compound should also be handled with the respect appropriate for a reactive halogenated phenol. Its usefulness as a synthetic reagent does not imply suitability for direct consumer exposure. Laboratory safety information identifies it as a substance requiring controlled handling, appropriate personal protection, and avoidance of unnecessary skin, eye, or inhalation exposure.

2-Bromo-5-chlorophenol is therefore a good example of how chemists see more in a small molecule than its name suggests. To a nonchemist, bromine and chlorine may appear to be merely two halogen atoms attached to a phenol. To a synthetic chemist, they can represent different stages in a construction plan: use one connection now, preserve another for later, and employ the hydroxyl group as a third route to molecular complexity.

The molecule's value lies in that controlled asymmetry. Bromine, chlorine, and hydroxyl are not simply three decorations on an aromatic ring. They are three chemically different instructions. Modern synthesis becomes powerful when chemists can read those instructions and decide in what order to follow them.

References

1. PubChem. 2-Bromo-5-chlorophenol. CAS 13659-23-9. Chemical identity and physicochemical information.

2. Miyaura, N.; Suzuki, A. (1995). "Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds." Chemical Reviews, 95, 2457-2483.
https://doi.org/10.1021/cr00039a007

3. Littke, A. F.; Fu, G. C. (2002). "Palladium-Catalyzed Coupling Reactions of Aryl Chlorides." Angewandte Chemie International Edition, 41, 4176-4211.
https://doi.org/10.1002/1521-3773(20021115)41:22%3C4176::AID-ANIE4176%3E3.0.CO;2-U

4. Smith, M. B. (2020). March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 8th ed. Wiley. Chemistry of phenols, aryl halides, and chemoselective transformations.

5. Cavallo, G.; Metrangolo, P.; Milani, R.; Pilati, T.; Priimagi, A.; Resnati, G.; Terraneo, G. (2016). "The Halogen Bond." Chemical Reviews, 116, 2478-2601.
https://doi.org/10.1021/acs.chemrev.5b00484