2-Bromo-2'-chloroacetophenone
[CAS 5000-66-8]

Identification

• Classification: Organic raw materials >> Ketone compound
• Name: 2-Bromo-2'-chloroacetophenone
• Synonyms: 2-Bromo-1-(2-chlorophenyl)ethan-1-one
• Molecular Formula: C₈H₆BrClO
• Molecular Weight: 233.49
• CAS Registry Number: 5000-66-8
• EC Number: 610-492-4
• SMILES: C1=CC=C(C(=C1)C(=O)CBr)Cl

Properties

• Density: 1.6$+/-$0.1 g/cm³ Calc.^*, 1.602 g/mL (Expl.)
• Boiling point: 248.9$+/-$15.0 $degree$C 760 mmHg (Calc.)^*, 337 $degree$C (Expl.)
• Flash point: 104.3$+/-$20.4 $degree$C (Calc.)^*
• Index of refraction: 1.584 (Calc.)^*, 1.59 (Expl.)

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

Safety Data

• Hazard Symbols: GHS05 Danger
• Risk Statements: H314
• Safety Statements: P260-P264-P280-P301+P330+P331-P302+P361+P354-P304+P340-P305+P354+P338-P316-P321-P363-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin corrosion	Skin Corr.	1B	H314
Serious eye damage	Eye Dam.	1	H318
Substances or mixtures corrosive to metals	Met. Corr.	1	H290
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H412
Acute toxicity	Acute Tox.	4	H302
Flammable liquids	Flam. Liq.	2	H225

• Transport Information: UN 2922

Discovery and Applications

2-Bromo-2'-chloroacetophenone is a halogenated aromatic ketone belonging to the acetophenone family, in which a phenyl ring is substituted with both a bromine atom and a chlorine atom at different positions, along with an acetyl group. Structurally, it can be described as an α-brominated acetophenone derivative combined with a chloro-substituted aromatic ring, making it a multifunctional electrophilic compound commonly encountered as an intermediate in organic synthesis.

Acetophenone derivatives are widely used in synthetic organic chemistry due to the reactivity of the carbonyl group and the ability of the α-position to undergo substitution reactions. In 2-bromo-2'-chloroacetophenone, the bromine atom at the α-position of the carbonyl (the carbon directly adjacent to the ketone group) significantly increases the electrophilicity of the molecule. This is because α-halogenated ketones are activated toward nucleophilic substitution and elimination reactions due to the electron-withdrawing effect of both the carbonyl and the halogen substituent.

The presence of a chlorine substituent on the aromatic ring further modifies the electronic properties of the molecule. Chlorine is an electron-withdrawing group through induction, although it can weakly donate electron density through resonance. In this compound, the chlorine substituent influences the reactivity of the aromatic system, generally deactivating the ring toward electrophilic aromatic substitution while directing incoming electrophiles to the ortho and para positions relative to itself.

The α-bromo ketone functionality is particularly important in organic synthesis because it serves as a versatile synthetic handle. The carbon–bromine bond at the α-position is relatively labile and can undergo nucleophilic substitution with a variety of nucleophiles, including amines, thiols, and oxygen nucleophiles. This allows α-bromo ketones to act as intermediates in the formation of heterocycles, substituted ketones, and more complex molecular architectures.

Compounds of this type are also known to participate in intramolecular cyclization reactions. When appropriately functionalized, α-halo ketones can undergo cyclization to form heterocyclic systems such as furans, thiophenes, or nitrogen-containing rings, depending on the nucleophile present. This reactivity makes 2-bromo-2'-chloroacetophenone a valuable building block in synthetic organic chemistry.

From a physicochemical perspective, 2-bromo-2'-chloroacetophenone is expected to be a relatively lipophilic aromatic compound with moderate polarity due to the presence of the carbonyl group. The halogen substituents increase molecular weight and polarizability, which can influence boiling point, melting point, and solubility characteristics. It is typically more soluble in organic solvents than in water.

The carbonyl group in the acetophenone moiety is polarized, with the carbon atom acting as an electrophilic center. This makes it susceptible to nucleophilic addition reactions under appropriate conditions. However, the presence of the α-bromo substituent often diverts reactivity toward substitution at the α-carbon rather than direct carbonyl addition, depending on reaction conditions and nucleophile strength.

In synthetic applications, α-halo ketones such as this compound are commonly used as intermediates in the preparation of pharmaceuticals, agrochemicals, and fine chemicals. Their dual reactivity at both the carbonyl group and the α-carbon allows for diverse chemical transformations in multistep synthesis pathways.

Overall, 2-bromo-2'-chloroacetophenone is a halogenated aromatic ketone characterized by an electrophilic carbonyl group, an α-bromo substituent, and a chloro-substituted phenyl ring. Its significance lies in its high synthetic versatility, particularly as a reactive intermediate in nucleophilic substitution and heterocycle-forming reactions in organic chemistry.

References

2022. Cenobamate. Pharmaceutical Substances.
URL: https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-03-0304