2-(2-Chloro-4-nitrophenoxy)acetic Acid: Properties & Applications

2-(2-Chloro-4-nitrophenoxy)acetic acid is a halogenated, nitro-substituted phenoxyacetic acid derivative widely used in organic synthesis and medicinal chemistry research as a versatile building block and reactive intermediate.

Chemical Name

2-(2-Chloro-4-nitrophenoxy)acetic acid

Molecular Formula

C₈H₆ClNO₅

Molecular Weight

231.59 g/mol

Functional Groups

Carboxylic acid, aryl ether (phenoxy), nitro, chloro

SKU / Product Code

A697060

Typical Application

Organic synthesis intermediate; medicinal chemistry building block

Chemical Structure and Properties

2-(2-Chloro-4-nitrophenoxy)acetic acid belongs to the phenoxyacetic acid family of compounds. Its structure features a phenoxy group bearing two electron-withdrawing substituents: a chloro group at the ortho position (C-2) and a nitro group at the para position (C-4) relative to the oxygen linkage. These substituents collectively render the aromatic ring highly electron-deficient, enhancing its reactivity toward nucleophilic aromatic substitution reactions.

The carboxylic acid moiety imparts aqueous solubility under basic conditions and serves as a versatile handle for further derivatization, including ester, amide, and acyl halide formation. The combination of these functional groups makes this compound a valuable multifunctional scaffold for synthetic chemists.

The compound has a molecular formula of C₈H₆ClNO₅ and a molecular weight of approximately 231.59 g/mol. It is typically encountered as a solid at room temperature. Solubility is generally favored in polar aprotic solvents such as DMF and DMSO, as well as in aqueous alkaline solutions.

Synthesis and Preparation

The synthesis of 2-(2-Chloro-4-nitrophenoxy)acetic acid is most commonly achieved via O-alkylation of 2-chloro-4-nitrophenol with a haloacetic acid derivative, such as chloroacetic acid or its sodium salt, under basic conditions. This classic Williamson ether synthesis proceeds through deprotonation of the phenol to generate the phenoxide nucleophile, which then displaces the halide of the alkylating agent to form the phenoxy ether linkage.

Reaction conditions typically involve a carbonate or hydroxide base (e.g., potassium carbonate or sodium hydroxide) in a polar solvent such as water, acetone, or DMF at elevated temperature. After reaction completion, acidification of the mixture precipitates or allows extraction of the free carboxylic acid product.

Alternative routes may involve nitration of a pre-formed phenoxyacetic acid intermediate, although regioselectivity considerations and the presence of sensitive functional groups may complicate this approach. The straightforward Williamson route is preferred for its efficiency and scalability.

Research Applications

2-(2-Chloro-4-nitrophenoxy)acetic acid serves primarily as a synthetic intermediate in pharmaceutical and agrochemical research. The electron-deficient aromatic ring is amenable to nucleophilic aromatic substitution (SNAr), allowing the chloro substituent to be displaced by a range of nitrogen, oxygen, or sulfur nucleophiles, thereby enabling the rapid construction of diverse molecular scaffolds.

The carboxylic acid group can be readily converted to esters, amides, or activated esters (e.g., N-hydroxysuccinimide esters) for coupling reactions in medicinal chemistry programs. Compounds derived from phenoxyacetic acid frameworks have demonstrated biological activities including herbicidal, anti-inflammatory, and antimicrobial properties in the scientific literature, making this class of intermediates of continued interest in drug discovery and crop-science research.

In agrochemical contexts, phenoxyacetic acid analogs bearing electron-withdrawing groups are explored as herbicide leads or as chemical biology tools for understanding auxin signaling pathways in plants, where structural analogs of natural auxin (indole-3-acetic acid) are frequently investigated.

Handling, Storage, and Safety Considerations

As with all nitroaromatic and halogenated organic compounds, appropriate laboratory safety precautions should be observed when handling 2-(2-Chloro-4-nitrophenoxy)acetic acid. Personal protective equipment (PPE) including gloves, safety glasses, and a laboratory coat should be worn at all times. Operations generating dust or aerosols should be conducted in a well-ventilated fume hood.

The compound should be stored in a cool, dry, well-ventilated location, away from incompatible materials such as strong oxidizing or reducing agents, strong bases, and sources of ignition. Container should be kept tightly closed when not in use to prevent moisture uptake and contamination.

Disposal must comply with local, regional, and national regulations governing chemical waste. Researchers should consult the Safety Data Sheet (SDS) supplied with the product for detailed hazard classification, first-aid measures, and disposal guidance before use. Specific GHS hazard classifications and H/P statements should be verified in the product SDS.

Frequently asked questions

What is 2-(2-Chloro-4-nitrophenoxy)acetic acid used for?

It is primarily used as a synthetic intermediate in pharmaceutical and agrochemical research. Its electron-deficient aromatic ring supports nucleophilic aromatic substitution reactions, and its carboxylic acid group enables further derivatization to esters, amides, and other functional derivatives.

What solvents are suitable for dissolving this compound?

2-(2-Chloro-4-nitrophenoxy)acetic acid is generally soluble in polar aprotic solvents such as DMSO and DMF. It can also dissolve in aqueous alkaline solutions due to the carboxylic acid group forming a soluble carboxylate salt under basic conditions. Solubility in water alone or in non-polar solvents is expected to be limited.

How should this compound be stored to maintain stability?

The compound should be stored in a tightly sealed container in a cool, dry, and well-ventilated area, away from strong oxidizers, reducing agents, and moisture. Adhering to the conditions specified in the product's Safety Data Sheet (SDS) is recommended to ensure long-term stability and safety.

Can 2-(2-Chloro-4-nitrophenoxy)acetic acid undergo nucleophilic aromatic substitution?

Yes. The presence of the electron-withdrawing nitro group at the para position activates the aromatic ring toward nucleophilic aromatic substitution (SNAr). The chloro group at the ortho position can act as the leaving group, allowing amines, alcohols, and thiols to be introduced under appropriate reaction conditions.

References

1. March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 4th ed.; Wiley: New York, 1992. (General reference for Williamson ether synthesis and nucleophilic aromatic substitution)
2. Smith, M. B. Organic Synthesis, 3rd ed.; Academic Press, 2010. (General synthetic methodology reference for phenoxyacetic acid derivatives)
3. Aladdin Scientific. Product Datasheet: 2-(2-Chloro-4-nitrophenoxy)acetic acid, SKU A697060. Aladdin Scientific, accessed 2024.

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