Production Method 1

6952-59-6

914250-82-1

Reaction Conditions

1.1 Reagents: Lithium diisopropylamide Solvents: Tetrahydrofuran ,  Hexane ;  1 h, -95 °C
1.2 Reagents: Hexachloroethane Solvents: Tetrahydrofuran ;  1 h, -95 °C; 16 h, -95 °C → rt
1.3 Reagents: Ammonium chloride Solvents: Water

Reference

Three groups good, four groups bad? Atropisomerism in ortho-substituted diaryl ethers

Betson, Mark S.; et al, Angewandte Chemie, 2006, 45(35), 5803-5807

Production Method 2

6952-59-6

914250-82-1

Reaction Conditions

1.1 Reagents: Lithium diisopropylamide Solvents: Tetrahydrofuran ;  1 h, -78 °C
1.2 Reagents: Hexachloroethane ;  16 h, 20 °C

Reference

Hindered diarylether and diarylsulfone bisphosphine ligands: atropisomerism and palladium complexes

Clayden, Jonathan; et al, Tetrahedron: Asymmetry, 2010, 21(11-12), 1355-1360

3-Bromo-2-chlorobenzonitrile Raw materials

• 3-Bromobenzonitrile

3-Bromo-2-chlorobenzonitrile Preparation Products

• 3-Bromo-2-chlorobenzonitrile (914250-82-1)

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  Yaling Zhang,Chunhui Dai,Shiwei Zhou,Bin Liu Chem. Commun., 2018,54, 10092-10095
• 2. Empowering microfluidics by micro-3D printing and solution-based mineral coating?
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• 4. EWOD-driven droplet microfluidic device integrated with optoelectronic tweezers as an automated platform for cellular isolation and analysis?
  Gaurav J. Shah,Eric P.-Y. Chiou,Ming C. Wu,Chang-Jin “CJ” Kim Lab Chip, 2009,9, 1732-1739
• 5. Evolution of cellulose into flexible conductive green electronics: a smart strategy to fabricate sustainable electrodes for supercapacitors
  Tengfei Yu,Yuehan Wu,Wei Li,Bin Li RSC Adv., 2014,4, 34134-34143

• Solvents and Organic Chemicals Organic Compounds Benzenoids Benzene and substituted derivatives Benzonitriles
• Solvents and Organic Chemicals Organic Compounds cyanides/Cyanides

Research Briefing on 3-Bromo-2-chlorobenzonitrile (CAS: 914250-82-1) in Chemical Biology and Pharmaceutical Applications

3-Bromo-2-chlorobenzonitrile (CAS: 914250-82-1) has recently emerged as a compound of significant interest in chemical biology and pharmaceutical research due to its versatile applications as a building block in drug discovery and material science. This briefing synthesizes the latest findings regarding its synthetic applications, biological activities, and potential therapeutic implications based on peer-reviewed studies published within the past two years.

Recent synthetic chemistry studies have highlighted the compound's utility in palladium-catalyzed cross-coupling reactions. A 2023 publication in Journal of Medicinal Chemistry demonstrated its effectiveness as a precursor for synthesizing novel kinase inhibitors, with the bromo and chloro substituents enabling sequential functionalization at orthogonal positions. The electron-withdrawing nitrile group was found to enhance the reactivity of adjacent halogens in Suzuki-Miyaura couplings while maintaining stability under diverse reaction conditions.

In pharmaceutical applications, researchers have incorporated 3-Bromo-2-chlorobenzonitrile into the development of targeted protein degraders (PROTACs). A 2024 study in ACS Chemical Biology reported its use as a linker component in cereblon-based degraders, where its rigid aromatic structure and halogen atoms facilitated optimal positioning of warhead and E3 ligase-binding moieties. The compound's metabolic stability and favorable physicochemical properties (cLogP = 2.8, TPSA = 33 ?2) make it particularly valuable for optimizing drug-like properties in these bifunctional molecules.

Structural biology investigations have revealed interesting interactions of derivatives containing this scaffold. Cryo-EM studies published in Nature Chemical Biology (2023) showed that bromo-chloro substitution pattern creates unique halogen bonding interactions with protein targets, particularly in allosteric binding sites. This property has been exploited in the design of selective modulators for challenging targets such as protein-protein interactions.

From a safety and ADME perspective, recent toxicological assessments indicate that while the compound itself shows moderate cytotoxicity (IC50 ≈ 50 μM in HepG2 cells), properly functionalized derivatives demonstrate improved safety profiles. Computational modeling studies suggest that metabolic dehalogenation represents the primary clearance pathway, with the nitrile group remaining stable under physiological conditions.

Ongoing research directions include exploring its use in DNA-encoded library synthesis and as a core scaffold for developing covalent inhibitors. The compound's commercial availability and well-characterized reactivity make it particularly attractive for high-throughput screening approaches. Future studies are expected to focus on expanding its applications in targeted drug delivery systems and as a versatile intermediate in continuous flow chemistry platforms.

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