2-Chloro-4-(3-fluorophenyl)benzoic Acid: Handling & Use Protocol
2-Chloro-4-(3-fluorophenyl)benzoic Acid: Handling & Use Protocol
2-Chloro-4-(3-fluorophenyl)benzoic acid is a halogenated biaryl aromatic carboxylic acid widely employed as a versatile building block in medicinal chemistry, agrochemical synthesis, and materials research.
- Chemical Name
- 2-Chloro-4-(3-fluorophenyl)benzoic acid
- SKU / Catalog Number
- C180187
- Molecular Formula
- C₁₃H₈ClFO₂
- Functional Groups
- Carboxylic acid, aryl chloride, aryl fluoride
- Primary Application
- Building block for cross-coupling reactions and pharmaceutical intermediate synthesis
- Recommended Storage
- Cool, dry place away from light and incompatible materials; seal tightly after use
Safety and Pre-Handling Considerations
Before working with 2-Chloro-4-(3-fluorophenyl)benzoic acid (SKU: C180187), review the Safety Data Sheet (SDS) provided with the shipment. As an aromatic carboxylic acid bearing halogen substituents, the compound may cause skin, eye, and respiratory irritation upon contact or inhalation of dust.
Recommended personal protective equipment (PPE):
- Chemical-resistant gloves (nitrile recommended)
- Safety goggles or face shield
- Lab coat and closed-toe shoes
- Work in a well-ventilated fume hood when weighing or dissolving
Store the compound in a tightly sealed container in a cool, dry location away from direct light, oxidising agents, and strong bases. Keep away from incompatible materials such as strong oxidisers and reactive metals.
Solubility and Solution Preparation
2-Chloro-4-(3-fluorophenyl)benzoic acid is an aromatic carboxylic acid and is expected to exhibit limited solubility in water due to its hydrophobic biaryl scaffold. It is typically soluble in common polar organic solvents.
Recommended solvents (in approximate order of preference):
- Dimethyl sulfoxide (DMSO)
- Dimethylformamide (DMF)
- Ethanol or methanol (with gentle warming if needed)
- Ethyl acetate
- Dichloromethane (DCM)
Preparation procedure:
- Tare an appropriate clean, dry glass vial on an analytical balance.
- Weigh the required quantity of compound using a micro-spatula; avoid breathing dust.
- Add solvent incrementally, starting at approximately 10 mg/mL, and vortex or stir gently until fully dissolved.
- If preparing aqueous buffer solutions, first dissolve in a minimal volume of DMSO, then dilute with buffer. Final DMSO concentration should be kept ≤1% v/v for cell-based assays to minimise solvent effects.
- Verify clarity of the solution before use; filter through a 0.22 µm PTFE syringe filter if particulates are observed.
Note: Specific solubility data for this compound were not confirmed in the source material; the guidance above is based on structural analogy with similar halogenated biaryl carboxylic acids. Verify experimentally.
Applications in Synthetic Chemistry
2-Chloro-4-(3-fluorophenyl)benzoic acid serves as a multifunctional building block exploiting three distinct reactive handles: the carboxylic acid group, the aryl chloride, and the aryl fluoride.
Key reaction types:
- Amide bond formation: The carboxylic acid can be activated with coupling reagents (e.g., HATU, EDCI/HOBt, or SOCl₂ to form the acyl chloride) to generate amides with primary or secondary amines — a common step in pharmaceutical lead optimisation.
- Cross-coupling reactions: The aryl chloride is amenable to palladium-catalysed cross-coupling reactions (e.g., Suzuki–Miyaura, Negishi, Buchwald–Hartwig) to introduce additional aryl, alkyl, or amino substituents.
- Nucleophilic aromatic substitution (SNAr): The aryl fluoride, activated by the electron-withdrawing carboxylic acid group on the adjacent ring, may participate in SNAr reactions with nucleophiles such as amines, alkoxides, or thiols under appropriate conditions.
- Esterification: Standard Fischer esterification or coupling-reagent-mediated esterification can convert the acid to methyl or ethyl esters for further manipulation.
This compound is particularly valued in fragment-based drug discovery and the construction of biaryl pharmacophores common in kinase inhibitor and GPCR modulator scaffolds.
Quality Control and Analytical Verification
Upon receipt of C180187, verify compound identity and purity before use in sensitive assays. The following analytical techniques are recommended:
- ¹H NMR and ¹³C NMR: Confirm regiochemistry of the biaryl scaffold, the chloro and fluoro substituents, and the carboxylic acid moiety. Compare chemical shifts with predicted values from structure.
- ¹⁹F NMR: Particularly informative for confirming the position and environment of the fluorine substituent on the meta-phenyl ring.
- HPLC (reverse-phase, C18 column): Assess purity; target ≥95% peak area at 254 nm UV detection.
- LC-MS: Confirm molecular weight; expected [M−H]⁻ ion consistent with molecular formula C₁₃H₈ClFO₂ (MW ≈ 250.66 g/mol).
- Melting point determination: Compare with literature or certificate of analysis value as a quick identity check.
Retain the certificate of analysis (CoA) provided with the product. If purity or identity does not meet expectations, contact Aladdin Scientific customer service referencing SKU C180187.
Waste Disposal and Environmental Considerations
Dispose of 2-Chloro-4-(3-fluorophenyl)benzoic acid and its solutions in accordance with local, institutional, and national regulations governing halogenated organic waste.
- Collect solid waste and concentrated solutions in labelled, chemically compatible waste containers designated for halogenated organic solvents.
- Do not pour down the drain or dispose of in general municipal waste streams.
- Contaminated gloves, spatulas, and wipes should be treated as chemical waste.
- Contact your institutional environmental health and safety (EHS) office for guidance specific to your facility.
No specific ecotoxicity data for this compound were available in the source material; apply the precautionary principle and treat as potentially harmful to aquatic organisms.
Frequently asked questions
What solvents are suitable for dissolving 2-Chloro-4-(3-fluorophenyl)benzoic acid?
DMSO and DMF are the most effective solvents for this compound. Alcohols such as ethanol or methanol can also be used, particularly with gentle warming. Aqueous solubility is expected to be low due to the lipophilic biaryl core; if aqueous formulations are needed, dissolve in DMSO first and dilute with buffer, keeping DMSO ≤1% v/v for biological assays.
Which cross-coupling reactions are compatible with the aryl chloride handle in this compound?
The aryl chloride in 2-Chloro-4-(3-fluorophenyl)benzoic acid is compatible with palladium-catalysed Suzuki–Miyaura coupling (with aryl boronic acids), Negishi coupling (with organozinc reagents), and Buchwald–Hartwig amination (with amines). Bulky phosphine ligands such as SPhos or XPhos are often recommended when using aryl chloride substrates to achieve good reactivity.
How should C180187 be stored to maintain stability?
Store 2-Chloro-4-(3-fluorophenyl)benzoic acid in a tightly sealed container in a cool, dry, and dark location. Keep away from strong oxidising agents, strong bases, and reactive metals. After opening, reseal immediately to prevent moisture uptake. Under these conditions, the compound is expected to be stable for an extended period; refer to the certificate of analysis for the specific retest date.
Is 2-Chloro-4-(3-fluorophenyl)benzoic acid suitable for biological or cell-based assays?
This compound is primarily positioned as a synthetic building block for chemical synthesis rather than a direct biological tool. If used in cell-based assays to evaluate intermediates or derivatives, ensure the DMSO vehicle concentration is minimised (≤0.1–1% v/v) and include appropriate solvent controls. No specific biological activity data for this compound were available in the source material.
What is the molecular weight of 2-Chloro-4-(3-fluorophenyl)benzoic acid and how do I calculate the amount needed for a reaction?
The molecular formula is C₁₃H₈ClFO₂, giving a molecular weight of approximately 250.66 g/mol. To calculate the mass needed: Mass (g) = Moles × MW. For example, to prepare 1 mmol, weigh approximately 250.7 mg. Use an analytical balance with readability ≤0.1 mg for accurate weighing of small quantities.
References
- March, J.; Smith, M. B. March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 7th ed.; Wiley: Hoboken, NJ, 2013.
- Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds. Chem. Rev. 1995, 95, 2457–2483. doi:10.1021/cr00039a007
- Buchwald, S. L.; Mauger, C.; Mignani, G.; Scholz, U. Industrial-Scale Palladium-Catalyzed Coupling of Aryl Chlorides and Amines — A Personal Account. Adv. Synth. Catal. 2006, 348, 23–39. doi:10.1002/adsc.200505325
- Aladdin Scientific Product Certificate of Analysis, SKU C180187, 2-Chloro-4-(3-fluorophenyl)benzoic acid. Aladdin Scientific, Shanghai.
Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.