6-(4-Chlorophenyl)-3-pyridinecarbaldehyde: Properties & Uses

6-(4-Chlorophenyl)-3-pyridinecarbaldehyde is a bifunctional heterocyclic aldehyde that combines an electron-withdrawing 4-chlorophenyl substituent with a reactive pyridine-3-carbaldehyde core, making it a valuable building block for medicinal chemistry, combinatorial synthesis, and the preparation of bioactive small molecules.

IUPAC Name

6-(4-Chlorophenyl)pyridine-3-carbaldehyde

Molecular Formula

C₁₂H₈ClNO

Molecular Weight

217.65 g/mol

Functional Groups

Aldehyde (–CHO), Pyridine ring, Chlorophenyl group

Key Reactivity

Electrophilic aldehyde suitable for condensation, reductive amination, Knoevenagel, and Wittig reactions

Catalog SKU

P730297

Supplier

Aladdin Scientific

Chemical Identity and Structure

6-(4-Chlorophenyl)-3-pyridinecarbaldehyde (CAS registry information should be confirmed with the supplier; see review flags) is a heterocyclic aromatic aldehyde belonging to the pyridine-carbaldehyde family. Its structure features a pyridine ring bearing an aldehyde group at the 3-position and a 4-chlorophenyl substituent at the 6-position, yielding a planar, conjugated framework.

The molecular formula is C₁₂H₈ClNO with a molecular weight of approximately 217.65 g/mol. The 4-chlorophenyl group exerts a combined inductive and resonance electron-withdrawing effect on the aromatic system, increasing the electrophilicity of the aldehyde carbonyl and the electron-deficiency of the pyridine ring. This electronic profile distinguishes it from simple benzaldehydes and unsubstituted nicotinaldehydes, enhancing its utility in diverse synthetic transformations.

The compound is typically obtained as a solid at room temperature. Storage under cool, dry conditions away from light and moisture is recommended to preserve aldehyde integrity and prevent condensation side reactions.

Synthesis and Reactivity

As an aldehyde-functionalized biaryl heterocycle, 6-(4-Chlorophenyl)-3-pyridinecarbaldehyde participates in a broad range of carbon–carbon and carbon–heteroatom bond-forming reactions. Its aldehyde group renders it amenable to the following key transformations:

• Reductive Amination: Reaction with primary or secondary amines in the presence of a reducing agent (e.g., NaBH₃CN or NaBH(OAc)₃) affords secondary or tertiary amines, useful motifs in drug-like molecule libraries.
• Knoevenagel Condensation: With active methylene compounds under basic conditions, the aldehyde undergoes Knoevenagel condensation to give α,β-unsaturated products that serve as Michael acceptors or fluorescent dye precursors.
• Wittig and Horner–Wadsworth–Emmons Reactions: Reaction with phosphonium ylides or phosphonate carbanions provides stilbene-type alkenes with extended conjugation, useful in materials science and biological probe development.
• Imine (Schiff Base) Formation: Condensation with amines yields aldimines or Schiff bases, which can be used as ligands for metal coordination chemistry or as intermediates toward ring-closing reactions.
• Nucleophilic Addition: Organometallic reagents (Grignard, organolithium) add to the aldehyde to give benzylic alcohols bearing the pyridylchlorophenyl scaffold.

The electron-deficient pyridine ring also makes this compound a potential partner in Suzuki–Miyaura or other cross-coupling reactions if halogen handles are introduced elsewhere in the target molecule, or it can serve as a directing group in C–H functionalization strategies.

Applications in Medicinal Chemistry and Drug Discovery

Pyridine-based aldehydes with aryl substituents represent an important class of scaffolds in drug discovery programs. The combination of a pyridine nitrogen (which can act as a hydrogen-bond acceptor or coordinate to metal centers in target proteins) with an aldehyde group and a para-chlorophenyl ring offers multiple vectors for diversification and optimization of biological activity.

Compounds derived from 6-(4-Chlorophenyl)-3-pyridinecarbaldehyde may be screened as kinase inhibitors, antimicrobial agents, or CNS-active compounds, given that chlorophenyl-pyridine motifs appear frequently in approved pharmaceuticals and clinical candidates. The aldehyde itself may also act as a covalent warhead or be elaborated into more complex heterocyclic systems via cyclization reactions.

In fragment-based drug discovery (FBDD) and high-throughput synthesis (HTS) library generation, bifunctional building blocks such as this compound are particularly valuable because a single scaffold enables rapid synthesis of structurally diverse analogue sets through variation at the aldehyde site while retaining the pharmacophoric biaryl core.

Note: Specific biological activity data for this compound are not available in the current source material and should not be assumed. Researchers should conduct independent screening and consult the primary literature.

Handling, Storage, and Safety Considerations

As with all aromatic aldehyde reagents, appropriate laboratory safety practices should be followed when handling 6-(4-Chlorophenyl)-3-pyridinecarbaldehyde. General precautions include:

• Personal Protective Equipment (PPE): Wear chemical-resistant gloves, laboratory coat, and safety glasses. Use in a well-ventilated fume hood to avoid inhalation of dust or vapors.
• Storage: Store in a tightly sealed container under cool (2–8 °C or as specified on the product label), dry conditions, away from light, heat, and incompatible materials such as strong oxidizers and strong bases.
• Stability: Aldehydes can be susceptible to oxidation to carboxylic acids and to self-condensation under improper storage. Confirm purity by NMR or HPLC before use in sensitive applications.
• Disposal: Dispose of waste in accordance with local, regional, and national regulations governing halogenated aromatic compounds.

Consult the supplier's Safety Data Sheet (SDS) for complete hazard classification, first-aid measures, and regulatory information specific to this compound before use.

Frequently asked questions

What is 6-(4-Chlorophenyl)-3-pyridinecarbaldehyde used for in research?

It is primarily used as a heterocyclic building block in medicinal chemistry and combinatorial synthesis. Its aldehyde group enables reductive amination, Knoevenagel condensation, Schiff base formation, and Wittig reactions, allowing rapid assembly of structurally diverse compound libraries for drug discovery screening.

How should 6-(4-Chlorophenyl)-3-pyridinecarbaldehyde be stored to maintain stability?

The compound should be stored in a tightly sealed container under cool (2–8 °C is typical for sensitive aldehydes), dry, and dark conditions, away from strong oxidizers and bases. Confirm purity by NMR or HPLC before use in critical applications, as aldehydes can oxidize or self-condense upon prolonged or improper storage.

What is the molecular weight of 6-(4-Chlorophenyl)-3-pyridinecarbaldehyde?

The molecular weight of 6-(4-Chlorophenyl)-3-pyridinecarbaldehyde is approximately 217.65 g/mol, based on the molecular formula C₁₂H₈ClNO.

Can 6-(4-Chlorophenyl)-3-pyridinecarbaldehyde be used as a ligand precursor in coordination chemistry?

Yes. The compound can undergo condensation with amines to form Schiff base ligands, which are widely used in metal coordination chemistry. The pyridine nitrogen and the imine nitrogen of the resulting Schiff base can chelate transition metals, making derivatives of this aldehyde valuable in catalysis and materials research.

Where can I purchase 6-(4-Chlorophenyl)-3-pyridinecarbaldehyde?

6-(4-Chlorophenyl)-3-pyridinecarbaldehyde is available from Aladdin Scientific under catalog SKU P730297. Contact Aladdin Scientific directly for pricing, availability, and bulk order inquiries.

References

1. March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure. Wiley-Interscience. General reference for aldehyde reactivity and condensation reactions.
2. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry. Oxford University Press. Reference for Wittig, reductive amination, and Knoevenagel reaction mechanisms.
3. Aladdin Scientific Product Page: 6-(4-Chlorophenyl)-3-pyridinecarbaldehyde, SKU P730297.

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