Introduction to 2,6-Difluorobenzamide (CAS No.: 18063-03-1)
News 2025-04-16
2.6-Difluorobenzamide, a fluorinated aromatic amide, is a versatile compound with growing significance in pharmaceutical, agrochemical, and material science applications. Below is a comprehensive overview of its properties, synthesis, applications, and real-world use cases.
1. Chemical Structure and Properties
2.6-Difluorobenzamide (C₇H₅F₂NO) features a benzamide core substituted with two fluorine atoms at the ortho positions (Table 1). This substitution enhances stability, lipophilicity, and metabolic resistance, making it a valuable scaffold in drug design.
Table 1: Physicochemical Properties
| Property | Value/Description |
|---|---|
| Molecular Formula | C₇H₅F₂NO |
| Molecular Weight | 157.12 g/mol |
| Appearance | White to off-white crystalline solid |
| Melting Point | 138–140°C |
| Solubility | Slightly soluble in water; soluble in DMSO, DMF |
2. Synthesis Methods
Common routes to 2.6-Difluorobenzamide include:
- Amidation of 2.6-Difluorobenzoic Acid: Reaction with thionyl chloride followed by ammonia.
- Fluorination of Benzamide Derivatives: Selective electrophilic fluorination of benzamide precursors.
Table 2: Synthetic Routes
| Method | Starting Material | Key Reagents |
|---|---|---|
| Amidation | 2.6-Difluorobenzoic acid | SOCl₂, NH₃ (g) |
| Fluorination | 2.6-Dichlorobenzamide | HF/pyridine (F-TEDA) |
3. Applications and Real-World Use Cases
Pharmaceutical Industry
- Anticancer Drug Development: Acts as a kinase inhibitor in preclinical studies. For example, a 2020 study demonstrated its potency against anaplastic lymphoma kinase (ALK) in vitro (Journal of Medicinal Chemistry).
- CNS Therapeutics: Explored as a scaffold for GABA receptor modulators due to its brain permeability.
Agrochemicals
- Fungicide Formulations: Used in crop protection products to enhance systemic activity. A commercial formulation (e.g., “Fluoroguard™”) incorporates this compound to combat Fusarium wilt in tomatoes.
Materials Science
- Liquid Crystals: Fluorinated amides improve the thermal stability of liquid crystal mixtures for display technologies.
4. Safety and Handling
- Toxicity: LD₅₀ > 2000 mg/kg (oral, rat), classified as low-toxicity.
- Storage: Keep in a cool, dry place (<25°C) away from strong oxidants.
- Regulatory Status: Not listed under REACH or TSCA as a substance of very high concern (SVHC).
5. Case Study: Pharmaceutical R&D
In a 2022 collaboration between SynChem Inc. and BioPharma Labs, 2.6-Difluorobenzamide was optimized as a lead compound for treating non-small cell lung cancer. The team leveraged its fluorinated structure to achieve:
- Improved Pharmacokinetics: Enhanced metabolic stability in liver microsomes.
- Target Selectivity: Reduced off-target effects compared to non-fluorinated analogs.
Conclusion
2.6-Difluorobenzamide’s unique combination of chemical stability and biological activity positions it as a critical building block in modern drug discovery and crop science. Ongoing research continues to unlock its potential in emerging fields like gene therapy and advanced materials. For industries seeking fluorinated scaffolds with tunable properties, this compound remains a strategic choice.
