2-Chloro-4-fluorocinnamic acid: Properties, Uses & Handling Guide

2-Chloro-4-fluorocinnamic acid is a halogen-substituted aromatic cinnamic acid derivative widely employed as a versatile building block in pharmaceutical synthesis, medicinal chemistry research, and the preparation of specialty fine chemicals.

Chemical Name

2-Chloro-4-fluorocinnamic acid

Molecular Formula

C₉H₆ClFO₂

Molecular Weight

200.59 g/mol

CAS Number

needs_review — please verify with supplier CoA

Functional Groups

α,β-unsaturated carboxylic acid; aryl chloride; aryl fluoride

Appearance

Typically a white to off-white crystalline solid

Storage Conditions

Store in a cool, dry, well-ventilated area away from light and moisture

Chemical Identity and Structure

2-Chloro-4-fluorocinnamic acid (SKU C299843) is a member of the cinnamic acid family characterised by a trans (E)-configured propenoic acid side chain attached to a phenyl ring bearing a chlorine substituent at the ortho (2-) position and a fluorine substituent at the para (4-) position. The combination of two different halogen atoms on the aromatic ring confers distinct electronic and steric properties relative to unsubstituted cinnamic acid, making this compound an attractive scaffold for structure–activity relationship (SAR) studies.

The α,β-unsaturated acid moiety provides multiple sites for further chemical transformation, including esterification, amide coupling, cycloaddition, and conjugate addition reactions, while the aryl halides (C–Cl and C–F bonds) can participate in cross-coupling reactions such as Suzuki–Miyaura, Heck, and Buchwald–Hartwig couplings under palladium or nickel catalysis.

Applications in Research and Synthesis

Pharmaceutical Intermediate: Halogenated cinnamic acid derivatives are well-established intermediates in the synthesis of bioactive molecules. The electron-withdrawing chloro and fluoro substituents modulate the acidity of the carboxylic acid and the reactivity of the double bond, and can improve metabolic stability and membrane permeability in drug candidates derived from this scaffold.

Cross-Coupling Chemistry: The aryl C–Cl bond can serve as an electrophilic partner in palladium-catalysed cross-coupling reactions, enabling the introduction of diverse aryl, alkenyl, or alkyl groups. The C–F bond, being stronger and less reactive under standard coupling conditions, can also be activated under specific Ni- or Pd-catalysed conditions for C–F functionalisation.

Peptide and Peptidomimetic Chemistry: The cinnamic acid core is occasionally incorporated into peptidomimetic frameworks or used to prepare cinnamoyl-amino acid conjugates for biological evaluation.

Material Science: Cinnamic acid derivatives have been studied for their photochemical [2+2] cycloaddition behaviour in crystalline and polymer matrices, with applications in photoresponsive materials. The halogen substituents can modulate photoreactivity and crystal packing.

Handling, Safety, and Storage Guidelines

Personal Protective Equipment (PPE): When handling 2-Chloro-4-fluorocinnamic acid, wear appropriate laboratory PPE including chemical-resistant gloves (e.g., nitrile), safety spectacles or goggles, and a laboratory coat. Work in a well-ventilated fume hood to minimise inhalation of dust or aerosols.

Storage: Store the compound in a tightly sealed container in a cool (typically 2–25 °C, confirm with the product label or CoA), dry location away from direct sunlight, moisture, and incompatible materials such as strong bases, strong oxidisers, and reducing agents. Desiccants may be used to prevent moisture uptake.

Spill and Disposal: In the event of a spill, contain the material, avoid generating dust, and clean up using appropriate inert absorbents. Dispose of waste in accordance with local, regional, and national environmental regulations. Consult the Safety Data Sheet (SDS) supplied with the product for full hazard classification, first-aid measures, and regulatory disposal guidance.

Note: Always refer to the current SDS for this product before use. Specific hazard data (GHS classification, H- and P-statements) should be sourced directly from the SDS provided by Aladdin Scientific.

Quality, Purity, and Specification Considerations

For research applications, the purity of 2-Chloro-4-fluorocinnamic acid is a critical parameter, as impurities may interfere with reaction yields, spectroscopic characterisation, and biological assay results. Aladdin Scientific provides a Certificate of Analysis (CoA) with each batch, detailing purity (typically assessed by HPLC or GC), appearance, and other identity confirmation data such as melting point or NMR.

Researchers should verify the E/Z isomeric purity of the compound. Cinnamic acid derivatives can isomerise under prolonged UV exposure or harsh reaction conditions. The predominant commercial form is the thermodynamically stable trans (E)-isomer; confirm isomeric identity via ¹H NMR (characteristic large coupling constant J ≈ 16 Hz for the vinyl protons in the E-isomer) or UV spectroscopy.

When sourcing for GMP-adjacent or regulated research contexts, request batch-specific CoA documentation and discuss custom purity requirements with Aladdin Scientific's technical sales team.

Recommended Workflow for Routine Use

Step 1 – Receipt and Inspection: Upon receipt, inspect the packaging for integrity. Record the batch number and consult the CoA to confirm purity and identity before use.

Step 2 – Weighing: Weigh the required quantity in a ventilated balance enclosure or fume hood to minimise dust exposure. Use an analytical balance for precise measurements required in sensitive assays.

Step 3 – Dissolution: 2-Chloro-4-fluorocinnamic acid is an aromatic carboxylic acid and is expected to dissolve in common organic solvents such as ethanol, methanol, DMSO, THF, dichloromethane, and ethyl acetate. Solubility in water is limited; aqueous solutions may be prepared using dilute base (e.g., sodium bicarbonate or sodium hydroxide solution) to form the corresponding carboxylate salt. Verify solubility in your specific solvent system before scaling up.

Step 4 – Reaction Setup: Follow standard laboratory practices for handling moisture- or air-sensitive reactions if coupling chemistry is intended. Use inert atmosphere (N₂ or Ar) where required by the specific protocol.

Step 5 – Post-Use Storage: Reseal the container tightly under inert atmosphere if the compound is moisture-sensitive, and return to recommended storage conditions promptly.

Frequently asked questions

What solvents are suitable for dissolving 2-Chloro-4-fluorocinnamic acid?

As an aromatic carboxylic acid, 2-Chloro-4-fluorocinnamic acid is expected to be soluble in polar organic solvents including ethanol, methanol, DMSO, THF, dichloromethane, and ethyl acetate. Aqueous solubility is low; dissolution in water can be facilitated by adding a dilute base to form the carboxylate salt. Always perform a small-scale solubility test before use in a new solvent system.

How can I confirm the E/Z isomeric identity of 2-Chloro-4-fluorocinnamic acid?

The most reliable method is ¹H NMR spectroscopy: the trans (E)-isomer exhibits a characteristic large vicinal coupling constant of approximately 16 Hz between the two vinyl protons, whereas the cis (Z)-isomer shows a smaller coupling constant of approximately 12 Hz. UV-Vis spectroscopy can also be used as a supporting technique. The commercial product is typically the thermodynamically stable E-isomer; confirm via the batch CoA.

Can 2-Chloro-4-fluorocinnamic acid be used in palladium-catalysed cross-coupling reactions?

Yes. The aryl C–Cl bond in 2-Chloro-4-fluorocinnamic acid can serve as an electrophilic coupling partner in palladium-catalysed reactions such as Suzuki–Miyaura, Heck, and Sonogashira couplings, although aryl chlorides generally require more active catalyst systems or elevated temperatures compared to aryl bromides or iodides. Optimisation of catalyst, ligand, base, and solvent is recommended for each specific coupling application.

What are the recommended storage conditions for this compound?

Store 2-Chloro-4-fluorocinnamic acid in a tightly sealed container in a cool, dry, well-ventilated area away from direct light and moisture. Avoid contact with strong oxidising agents, strong bases, and reducing agents. Refer to the product label and SDS for batch-specific storage temperature requirements.

Where can I find the Safety Data Sheet (SDS) for 2-Chloro-4-fluorocinnamic acid (C299843)?

The SDS for C299843 is available on the Aladdin Scientific product page for this compound. You may also request it directly from Aladdin Scientific customer service. Always consult the current SDS before handling any chemical reagent.

References

1. March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure. Wiley-Interscience. General reference for α,β-unsaturated acid reactivity and cross-coupling chemistry.
2. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry. Oxford University Press. Reference for cinnamic acid derivatives, E/Z isomerism and NMR characterisation.
3. Aladdin Scientific. Certificate of Analysis and Safety Data Sheet for 2-Chloro-4-fluorocinnamic acid, SKU C299843. Aladdin Scientific internal documentation.

Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.