4-Chloro-3-nitrobenzaldehyde: Properties, Synthesis & Uses

4-Chloro-3-nitrobenzaldehyde is a bifunctionally substituted aromatic aldehyde widely employed as a versatile building block in pharmaceutical synthesis, agrochemical research, and the preparation of dyes and advanced functional materials.

IUPAC Name

4-Chloro-3-nitrobenzaldehyde

Molecular Formula

C₇H₄ClNO₃

Molecular Weight

185.56 g/mol

CAS Number

16588-34-4

Appearance

Pale yellow to yellow crystalline solid

Key Functional Groups

Aldehyde (–CHO), Nitro (–NO₂), Chloro (–Cl)

SKU

C132273

Chemical Structure and Physical Properties

4-Chloro-3-nitrobenzaldehyde (CAS 16588-34-4, MW 185.56 g/mol, molecular formula C₇H₄ClNO₃) is an aromatic aldehyde bearing three distinct substituents on the benzene ring: an aldehyde group at the para position (C-4 relative to chlorine numbering) serving as an electrophilic carbonyl center, a chlorine atom at C-4, and a strongly electron-withdrawing nitro group at the C-3 (meta) position. The combination of the chloro and nitro groups makes the ring electron-deficient overall, significantly activating the carbonyl toward nucleophilic addition and facilitating nucleophilic aromatic substitution (SNAr) at the carbon bearing chlorine.

The compound typically presents as a pale yellow to yellow crystalline solid at room temperature. The nitro group ortho to the chlorine exerts a powerful inductive and mesomeric electron-withdrawing effect, lowering the electron density at the aldehyde carbon and around the ring. This electronic profile is responsible for the reagent's high reactivity in condensation, reduction, and cross-coupling chemistry. Storage under cool, dry, and well-ventilated conditions away from reducing agents and strong bases is recommended to maintain purity.

Synthesis and Key Reactions

4-Chloro-3-nitrobenzaldehyde is most commonly prepared by nitration of 4-chlorobenzaldehyde using a mixed acid system (concentrated nitric acid and sulfuric acid) under controlled low-temperature conditions. The electron-withdrawing aldehyde group directs incoming nitro groups predominantly to the meta position, while the chloro substituent further influences regioselectivity, resulting in preferential nitration at the C-3 position to furnish the target compound. Careful temperature control is essential to minimize over-nitration and dialdehyde by-product formation.

The reagent participates in a broad range of synthetic transformations:
• Knoevenagel condensation: reaction with active methylene compounds (e.g., malononitrile, malonic acid derivatives) to produce arylidene intermediates used in heterocyclic synthesis.
• Reductive amination: the aldehyde undergoes reductive amination with primary or secondary amines in the presence of reducing agents such as sodium cyanoborohydride, providing substituted benzylamines.
• Nucleophilic aromatic substitution (SNAr): the chlorine atom, activated by the ortho-nitro group, is displaced by a variety of nucleophiles (amines, thiols, alkoxides) under mild conditions.
• Wittig and Horner–Wadsworth–Emmons reactions: condensation with phosphorus ylides to extend the carbon framework via vinyl linkages.
• Schiff base formation: condensation with primary amines to afford imines (Schiff bases) that serve as ligands in coordination chemistry or as pharmacophores.

Research and Industrial Applications

The multifunctional nature of 4-Chloro-3-nitrobenzaldehyde makes it a valuable intermediate across several research domains:

Pharmaceutical and Medicinal Chemistry: The compound serves as a precursor in the synthesis of biologically active molecules. The aldehyde and nitro groups can be selectively transformed to introduce amine, hydroxyl, or heterocyclic moieties. Reduction of the nitro group to an amine gives 4-chloro-3-aminobenzaldehyde, which can be cyclized into benzimidazoles, indazoles, quinazolines, and other privileged scaffolds found in drug candidates. The electrophilic chlorine enables further diversification via SNAr without requiring harsh reaction conditions.

Agrochemical Research: Nitrobenzaldehyde derivatives are used as starting materials for the preparation of herbicides, fungicides, and insecticides. The reactive handles of this substrate allow rapid construction of diverse compound libraries for biological screening.

Dye and Pigment Chemistry: Aromatic aldehydes bearing electron-withdrawing groups are employed as building blocks for azo dyes and push–pull chromophores. 4-Chloro-3-nitrobenzaldehyde can be condensed with heterocyclic or amine coupling components to tune the absorption properties of the resulting colorants.

Materials Science: Schiff bases and Knoevenagel products derived from this aldehyde are investigated as fluorescent probes, nonlinear optical (NLO) materials, and metal–organic framework (MOF) linkers, owing to the electron-deficient aromatic core that facilitates intramolecular charge transfer.

Handling, Safety, and Storage

As with most nitroaromatic compounds, 4-Chloro-3-nitrobenzaldehyde should be handled with appropriate precautions. Researchers should consult the Safety Data Sheet (SDS) provided by Aladdin Scientific before use. General guidelines include:

• Personal protective equipment (PPE): Wear chemical-resistant gloves, safety goggles, and a laboratory coat. Work in a well-ventilated fume hood to avoid inhalation of dust or vapors.
• Storage: Store in a tightly sealed container in a cool (2–25 °C), dry, and well-ventilated area, away from strong oxidizing agents, reducing agents, strong acids, and strong bases. Protect from light to prevent photodegradation.
• Incompatibilities: Avoid contact with strong nucleophiles at elevated temperatures without appropriate controls; the nitro group can participate in unintended reduction reactions in the presence of reducing agents.
• Disposal: Dispose of in accordance with local, regional, and national regulations for aromatic nitro compound waste. Do not pour into drains or waterways.

Specific hazard classifications, GHS pictograms, first-aid measures, and regulatory information are detailed in the official SDS. Always verify current SDS information before use.

Why Choose Aladdin Scientific (SKU C132273)

Aladdin Scientific offers 4-Chloro-3-nitrobenzaldehyde (SKU C132273) as a high-purity research reagent suitable for demanding synthetic applications. Each lot is quality-controlled to ensure consistent purity, enabling reproducible experimental outcomes. Key advantages of sourcing from Aladdin Scientific include:

• Reliable purity: Rigorous analytical testing (including HPLC and NMR verification) ensures batch-to-batch consistency for critical research applications.
• Detailed documentation: Certificate of Analysis (CoA), Safety Data Sheet (SDS), and full chemical characterization data are available for every lot.
• Flexible quantities: Available in multiple pack sizes to accommodate both small-scale discovery chemistry and larger preparative needs.
• Expert support: Aladdin's technical team is available to assist with reagent selection, compatibility questions, and application guidance.

Researchers working in medicinal chemistry, materials science, or agrochemical synthesis can rely on Aladdin Scientific's supply chain for timely delivery and documentation compliance.

Frequently asked questions

What is 4-Chloro-3-nitrobenzaldehyde used for in organic synthesis?

4-Chloro-3-nitrobenzaldehyde is used as a multifunctional building block in the synthesis of pharmaceuticals, agrochemicals, dyes, and functional materials. Its aldehyde group participates in condensation reactions (Knoevenagel, Wittig, reductive amination, and Schiff base formation), while the chlorine atom can be displaced via nucleophilic aromatic substitution (SNAr) facilitated by the adjacent nitro group. Reduction of the nitro group provides access to amino-benzaldehyde derivatives for heterocyclic synthesis.

How should 4-Chloro-3-nitrobenzaldehyde be stored to maintain stability?

The compound should be stored in a tightly sealed container in a cool (2–25 °C), dry, dark, and well-ventilated location, away from reducing agents, strong acids, strong bases, and oxidizing agents. Protection from light helps prevent photodegradation of the aldehyde functional group. Always refer to the current SDS for specific storage requirements.

What is the molecular weight and CAS number of 4-Chloro-3-nitrobenzaldehyde?

4-Chloro-3-nitrobenzaldehyde has a molecular weight of 185.56 g/mol and the CAS registry number 16588-34-4. Its molecular formula is C₇H₄ClNO₃.

Can 4-Chloro-3-nitrobenzaldehyde undergo nucleophilic aromatic substitution?

Yes. The chlorine substituent in 4-Chloro-3-nitrobenzaldehyde is activated toward nucleophilic aromatic substitution (SNAr) by the ortho-nitro group, which strongly withdraws electron density from the ring and stabilizes the Meisenheimer complex intermediate. This allows amines, thiols, and alkoxides to displace the chlorine under relatively mild conditions, providing a versatile handle for further functionalization.

Is a Certificate of Analysis available for Aladdin SKU C132273?

Yes. Aladdin Scientific provides a Certificate of Analysis (CoA) for each lot of 4-Chloro-3-nitrobenzaldehyde (SKU C132273), detailing purity, analytical test results, and lot-specific data. The SDS is also available and should be reviewed before handling the compound.

References

1. March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 4th ed.; Wiley-Interscience: New York, 1992. (General reference for SNAr and aldehyde condensation reactions.)
2. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012. (Reference for nitration regioselectivity and electrophilic aromatic substitution.)
3. Aladdin Scientific. Product page: 4-Chloro-3-nitrobenzaldehyde, SKU C132273. https://www.aladdin-e.com (accessed 2024).

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