1-(4-Fluorophenyl)-1H-imidazole-4-carboxylic Acid: Properties & Uses
1-(4-Fluorophenyl)-1H-imidazole-4-carboxylic Acid: Properties & Uses
1-(4-Fluorophenyl)-1H-imidazole-4-carboxylic acid is a fluorine-bearing N-aryl imidazole carboxylic acid that serves as a versatile heterocyclic building block in medicinal chemistry, organic synthesis, and pharmaceutical research.
- Chemical Name
- 1-(4-Fluorophenyl)-1H-imidazole-4-carboxylic acid
- Core Scaffold
- N-aryl substituted imidazole with a carboxylic acid at the 4-position
- Key Functional Groups
- Carboxylic acid (-COOH), imidazole ring, para-fluorophenyl group
- Primary Application
- Heterocyclic building block for drug discovery and organic synthesis
- Aladdin SKU
- H728937
- Compound Class
- Fluorinated N-arylimidazole carboxylic acid
Chemical Structure and Key Properties
1-(4-Fluorophenyl)-1H-imidazole-4-carboxylic acid is characterized by an imidazole ring bearing a 4-fluorophenyl substituent at the N-1 nitrogen and a carboxylic acid group at the C-4 position. This combination of a five-membered aromatic heterocycle, an electron-withdrawing fluorine atom on the phenyl ring, and a free carboxylic acid group confers distinctive physicochemical properties to the molecule.
The para-fluorine substituent on the phenyl ring reduces electron density across the aromatic system, increasing metabolic stability relative to unsubstituted phenyl analogs—a property highly valued in medicinal chemistry. The carboxylic acid moiety provides a handle for further chemical elaboration, including amide coupling, esterification, and coordination chemistry. The imidazole ring itself is amphoteric, capable of acting as both a hydrogen bond donor and acceptor, which contributes to favorable interactions with biological targets.
These structural features collectively make this compound a well-defined, stable solid suitable for storage and handling under standard laboratory conditions.
Synthesis Relevance and Role as a Building Block
In synthetic chemistry, 1-(4-Fluorophenyl)-1H-imidazole-4-carboxylic acid is primarily employed as an advanced intermediate and building block. The free carboxylic acid is amenable to standard coupling reagent-mediated amide bond formation (e.g., using EDC/HOBt, HATU, or HBTU), enabling rapid construction of amide libraries for structure–activity relationship (SAR) studies.
Esterification of the carboxylic acid under acidic or basic conditions yields methyl or ethyl esters, which can serve as protected intermediates or prodrug motifs. The compound can also participate in reactions that exploit the imidazole nitrogen atoms, such as alkylation or metal coordination, broadening its synthetic utility.
The introduction of the 4-fluorophenyl group at N-1 is typically achieved via N-arylation strategies, including copper-catalyzed or palladium-catalyzed cross-coupling reactions, or through direct condensation approaches. As a commercially available compound from Aladdin Scientific (SKU: H728937), researchers can bypass multi-step synthesis and access this scaffold directly for downstream functionalization.
Research and Pharmaceutical Applications
Fluorinated N-arylimidazole carboxylic acids and their derivatives occupy an important niche in pharmaceutical research. The imidazole ring is a privileged scaffold found in numerous bioactive molecules, including antifungal agents, enzyme inhibitors, and receptor ligands. The presence of the carboxylic acid group allows this compound to serve as a precursor to a broad range of pharmacologically relevant amides, esters, and heterocyclic derivatives.
The 4-fluorophenyl moiety is a widely employed bioisostere in drug design. Fluorine substitution at the para position of a phenyl ring modulates lipophilicity, pKa, and membrane permeability, and can enhance binding affinity to protein targets through specific C–F···H–N or C–F···π interactions. These properties make fluorinated imidazole carboxylic acids attractive starting materials in fragment-based drug discovery (FBDD) and high-throughput screening campaigns.
Beyond drug discovery, this class of compounds is used in materials science and coordination chemistry as ligands for metal-organic frameworks (MOFs) and other supramolecular architectures, owing to the dual donor capacity of the imidazole and carboxylate groups.
Handling, Storage, and Safety Considerations
As with most research-grade carboxylic acid reagents, appropriate laboratory precautions should be observed when handling 1-(4-Fluorophenyl)-1H-imidazole-4-carboxylic acid. Standard personal protective equipment (PPE), including gloves, safety glasses, and a laboratory coat, is recommended to prevent skin and eye contact.
The compound should be stored in a cool, dry, and well-ventilated area, away from incompatible materials such as strong bases and oxidizing agents. Containers should be kept tightly sealed when not in use to prevent moisture absorption and degradation.
Researchers should consult the Safety Data Sheet (SDS) provided by Aladdin Scientific for complete hazard information, first aid measures, and disposal guidelines prior to use. Waste disposal must comply with applicable local, regional, and national regulations governing fluorinated organic compounds.
Frequently asked questions
What is 1-(4-Fluorophenyl)-1H-imidazole-4-carboxylic acid used for in research?
This compound is primarily used as a heterocyclic building block in medicinal chemistry and organic synthesis. Its carboxylic acid group enables amide coupling and esterification reactions, making it valuable for constructing compound libraries for drug discovery, SAR studies, and fragment-based screening programs.
Why is the 4-fluorophenyl substituent important in this molecule?
The para-fluorine atom is an electron-withdrawing group that modulates the electronic properties of the aryl ring, improving metabolic stability and influencing lipophilicity and membrane permeability. In drug design, the 4-fluorophenyl group is a common bioisostere that can enhance binding affinity and pharmacokinetic profiles of drug candidates.
How should I store 1-(4-Fluorophenyl)-1H-imidazole-4-carboxylic acid?
The compound should be stored in a tightly sealed container in a cool, dry, and well-ventilated location, away from strong bases and oxidizing agents. Always refer to the Aladdin Scientific SDS for specific storage temperature recommendations and hazard information before use.
Can the carboxylic acid group be used for amide bond formation?
Yes. The free carboxylic acid in this compound is well-suited for standard amide coupling reactions using common activating reagents such as EDC/HOBt, HATU, or HBTU. This makes it a versatile intermediate for generating amide derivatives in combinatorial and medicinal chemistry workflows.
References
- Comprehensive Medicinal Chemistry III, Elsevier. General principles of fluorine in drug design and N-arylimidazole scaffolds.
- March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 7th ed. Wiley. Amide bond formation and carboxylic acid activation methods.
- Aladdin Scientific product page for H728937: 1-(4-Fluorophenyl)-1H-imidazole-4-carboxylic acid.
Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.
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