2-Bromo-1-(4-chloro-2-fluorophenyl)ethanone
[CAS# 725743-41-9]

Identification

• Classification: Organic raw materials >> Ketone compound
• Name: 2-Bromo-1-(4-chloro-2-fluorophenyl)ethanone
• Molecular Formula: C₈H₅BrClFO
• Molecular Weight: 251.48
• CAS Registry Number: 725743-41-9
• SMILES: C1=CC(=C(C=C1Cl)F)C(=O)CBr

Properties

• Density: 1.7±0.1 g/cm³ Calc.^*
• Boiling point: 284.7±25.0 ºC 760 mmHg (Calc.)^*
• Flash point: 126.0±23.2 ºC (Calc.)^*
• Index of refraction: 1.564 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319-H335
• Precautionary Statements: P261-P305+P351+P338

Discovory and Applicatios

2-Bromo-1-(4-chloro-2-fluorophenyl)ethanone is a halogenated aryl ketone featuring a bromine atom at the α-position of the carbonyl group and a 4-chloro-2-fluorophenyl moiety. The combination of halogen substituents on the aromatic ring and the α-bromo ketone functionality makes this compound a versatile intermediate in organic synthesis, particularly for the preparation of heterocycles, pharmaceuticals, and agrochemicals.

The α-bromo ketone group is highly reactive toward nucleophiles, enabling substitution reactions with amines, thiols, or alcohols to generate substituted ketones, amides, or thioethers. This reactivity also allows cyclization reactions to form various five- and six-membered heterocycles, including pyrroles, thiazoles, and imidazoles. The 4-chloro-2-fluorophenyl group can influence the electronic properties of the molecule, enhancing lipophilicity and potentially improving biological activity when incorporated into drug candidates.

Typical synthetic routes start from 4-chloro-2-fluoroacetophenone, which undergoes α-bromination using N-bromosuccinimide (NBS) under controlled conditions to yield 2-bromo-1-(4-chloro-2-fluorophenyl)ethanone. Reaction conditions, such as temperature and solvent, are carefully chosen to ensure selective monobromination and prevent overbromination or side reactions.

In medicinal chemistry, α-bromo ketones like this compound serve as intermediates for the synthesis of antiviral, anticancer, and antibacterial agents. The halogenated phenyl ring allows for additional functionalization through cross-coupling reactions such as Suzuki or Sonogashira coupling, further expanding the structural diversity for lead optimization.

References

CN-118561872-A (2023) Pyrimidopyridine biological inhibitor, preparation method and application thereof. Link

WO-2024178304-A1 (2023) KRAS modulators and preparation methods thereof. Link

TW-202430184-A (2022) Crystalline form of KRAS G12D inhibitors and preparation method thereof. Link