3,4-Difluoro-5-methoxybenzoic Acid: Properties & Uses

3,4-Difluoro-5-methoxybenzoic acid is a fluorine-rich aromatic carboxylic acid that serves as a versatile synthetic building block in medicinal chemistry, agrochemical research, and the preparation of advanced functional materials.

IUPAC Name

3,4-Difluoro-5-methoxybenzoic acid

Molecular Formula

C₈H₆F₂O₃

Molecular Weight

188.13 g/mol

Functional Groups

Carboxylic acid, two aromatic fluorine substituents, methoxy group

Key Application

Fluorinated aromatic building block for drug discovery and fine chemical synthesis

Aladdin SKU

D731847

Chemical Identity and Structure

3,4-Difluoro-5-methoxybenzoic acid is a substituted benzoic acid bearing two adjacent fluorine atoms at the 3- and 4-positions and a methoxy (–OCH₃) group at the 5-position of the aromatic ring, with a carboxylic acid (–COOH) group at the 1-position. Its molecular formula is C₈H₆F₂O₃ and its molecular weight is approximately 188.13 g/mol.

The combination of electron-withdrawing fluorine atoms and a moderately electron-donating methoxy group creates a distinctive electronic environment on the ring, influencing both reactivity and binding interactions with biological targets. This pattern of substitution is encountered in several pharmacophore design strategies, making the compound a structurally interesting scaffold for synthetic chemists.

Physicochemical Properties and Stability

As an aromatic carboxylic acid carrying electron-withdrawing fluorine substituents, 3,4-Difluoro-5-methoxybenzoic acid is expected to display a moderately low pKa relative to unsubstituted benzoic acid, reflecting the inductive effect of the two fluorine atoms. The compound is typically a solid at room temperature and is expected to be soluble in polar organic solvents such as dimethyl sulfoxide (DMSO), dimethylformamide (DMF), ethanol, and ethyl acetate, with limited solubility in water.

The compound should be stored in a cool, dry environment away from strong bases and oxidizing agents. Under standard laboratory storage conditions in a sealed container, the material is expected to be stable for an extended period. Users should consult the product-specific Certificate of Analysis (CoA) supplied by Aladdin Scientific for confirmed purity, melting point, and storage recommendations.

Synthetic Applications and Reactivity

The carboxylic acid group of 3,4-Difluoro-5-methoxybenzoic acid provides a versatile handle for a wide range of synthetic transformations. It can be converted to acid chlorides, activated esters, amides, and esters, enabling coupling with amines, alcohols, and other nucleophiles in the construction of complex molecular architectures.

The aromatic fluorine atoms at the 3- and 4-positions are amenable to nucleophilic aromatic substitution (SNAr) reactions under appropriate conditions, allowing introduction of nitrogen, oxygen, or sulfur nucleophiles. This dual reactivity — from both the carboxyl group and the ring fluorines — makes the compound a particularly flexible intermediate in multi-step synthesis programs, including the preparation of fluorinated pharmaceuticals, agrochemicals, and materials science intermediates.

The methoxy group can also serve as a protecting group for a phenolic hydroxyl, or alternatively as a directing group in further electrophilic or metalation-based functionalization reactions.

Applications in Medicinal Chemistry and Drug Discovery

Fluorine substitution in drug candidates is a well-established strategy in medicinal chemistry. Fluorine atoms can improve metabolic stability by blocking sites of cytochrome P450-mediated oxidation, modulate lipophilicity (logP), enhance membrane permeability, and strengthen binding affinity through C–F···H–N or C–F···carbonyl electrostatic interactions with protein targets.

3,4-Difluoro-5-methoxybenzoic acid, with its combination of vicinal difluoro substitution and a methoxy group, is a useful fragment for building drug-like molecules targeting a variety of enzyme and receptor families. It may be employed in fragment-based drug discovery (FBDD) as a starting fragment or as an advanced intermediate in the synthesis of lead compounds and candidate molecules. Researchers in oncology, infectious disease, and CNS drug discovery may find this scaffold particularly relevant.

Handling, Safety, and Ordering Information

As with all laboratory reagents, standard safe-handling practices should be observed when working with 3,4-Difluoro-5-methoxybenzoic acid. Appropriate personal protective equipment (PPE) — including lab coat, chemical-resistant gloves, and eye protection — should be worn at all times. Work should be conducted in a well-ventilated area or under a fume hood. Users must consult the Safety Data Sheet (SDS) provided by Aladdin Scientific before use.

3,4-Difluoro-5-methoxybenzoic acid is available from Aladdin Scientific under SKU D731847. For confirmed purity specifications, lot-specific Certificates of Analysis, bulk pricing, and availability, please contact Aladdin Scientific directly or visit the product page on the Aladdin website.

Frequently asked questions

What is 3,4-Difluoro-5-methoxybenzoic acid used for?

It is primarily used as a fluorinated aromatic building block in synthetic chemistry, particularly in medicinal chemistry and agrochemical research. Its carboxylic acid group and ring fluorines allow diverse chemical transformations including amide coupling, esterification, and nucleophilic aromatic substitution.

In which solvents does 3,4-Difluoro-5-methoxybenzoic acid dissolve?

The compound is expected to dissolve well in polar aprotic solvents such as DMSO and DMF, and in polar protic solvents such as ethanol. Solubility in water is expected to be limited due to the hydrophobic fluorine and methoxy substituents. Always verify solubility experimentally for your specific application.

How should 3,4-Difluoro-5-methoxybenzoic acid be stored?

The compound should be stored in a tightly sealed container in a cool, dry place, away from moisture, strong oxidizing agents, and strong bases. Refer to the Aladdin Scientific Safety Data Sheet and Certificate of Analysis for product-specific storage temperature recommendations.

Why is fluorine substitution important in drug discovery?

Fluorine substitution can significantly improve drug candidates by enhancing metabolic stability, modulating lipophilicity, improving membrane permeability, and strengthening target binding through unique electrostatic interactions. These properties make fluorinated building blocks like 3,4-Difluoro-5-methoxybenzoic acid highly valuable in pharmaceutical research.

What is the Aladdin SKU for 3,4-Difluoro-5-methoxybenzoic acid?

3,4-Difluoro-5-methoxybenzoic acid is available from Aladdin Scientific under SKU D731847. Contact Aladdin Scientific or visit the product page for current pricing, pack sizes, and availability.

References

1. Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Fluorine in medicinal chemistry. Chemical Society Reviews, 2008, 37, 320–330. doi:10.1039/b610213c
2. O'Hagan, D. Understanding organofluorine chemistry. An introduction to the C–F bond. Chemical Society Reviews, 2008, 37, 308–319. doi:10.1039/b711844a
3. Aladdin Scientific. Product page: 3,4-Difluoro-5-methoxybenzoic acid, SKU D731847. Aladdin Scientific Corp.

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