Methyl 3-(3-chlorophenyl)-3-oxopropanoate: Properties & Uses

Methyl 3-(3-chlorophenyl)-3-oxopropanoate is a versatile β-ketoester building block bearing a meta-chlorophenyl ketone moiety, widely employed as a synthetic intermediate in pharmaceutical and agrochemical research.

Chemical Name

Methyl 3-(3-chlorophenyl)-3-oxopropanoate

SKU

M700284

Molecular Formula

C10H9ClO3

Molecular Weight

212.63 g/mol

Compound Class

β-Ketoester (aromatic)

Key Functional Groups

Aryl ketone, methyl ester, active methylene

Chemical Structure and Physical Properties

Methyl 3-(3-chlorophenyl)-3-oxopropanoate (CAS not confirmed in source material; flagged for review) is an aromatic β-ketoester consisting of a 3-chlorophenyl carbonyl group linked to a methyl ester via an active methylene (–CH₂–) bridge. Its molecular formula is C₁₀H₉ClO₃, giving a molecular weight of approximately 212.63 g/mol.

The active methylene protons flanked by two carbonyl groups exhibit markedly enhanced acidity (estimated pKa ~11–13 in DMSO for analogous β-ketoesters), enabling facile deprotonation and subsequent alkylation or acylation reactions. The meta-chloro substituent on the phenyl ring exerts moderate electron-withdrawing effects through inductive pathways, activating the carbonyl toward nucleophilic addition while also influencing enol–keto tautomeric equilibria.

The compound is expected to be a pale yellow to colorless liquid or low-melting solid at ambient conditions; specific melting/boiling point data should be verified against the certificate of analysis supplied with SKU M700284.

Synthesis and Preparation Methods

Methyl 3-(3-chlorophenyl)-3-oxopropanoate is classically prepared via a Claisen-type condensation between 3-chloroacetophenone and dimethyl carbonate (or methyl acetate) in the presence of a strong base such as sodium hydride or sodium methoxide. The reaction proceeds through deprotonation of the methyl ketone at the α-position, followed by acylation with the carbonate ester to furnish the β-ketoester in moderate-to-good yields.

Alternatively, condensation of 3-chlorobenzoyl chloride with malonic acid half-esters (e.g., monomethyl malonate) under Meldrum's acid-derived routes or Knoevenagel-type sequences can provide access to this scaffold. Reaction conditions, including solvent choice (THF, DMF, or toluene), temperature, and base stoichiometry, must be optimized to minimize di-acylation byproducts.

Researchers purchasing SKU M700284 from Aladdin Scientific receive the compound ready for use, eliminating multi-step in-house preparation and ensuring batch-to-batch consistency.

Research and Synthetic Applications

As a bifunctional β-ketoester, Methyl 3-(3-chlorophenyl)-3-oxopropanoate serves as a versatile precursor in heterocyclic synthesis. The active methylene group participates in condensations with aldehydes, amines, hydrazines, and ureas to construct medicinally relevant ring systems including pyrazoles, pyrimidines, dihydropyridines (Hantzsch), and isoxazoles.

The 3-chlorophenyl group is particularly valuable in medicinal chemistry: the halogen atom can serve as a handle for downstream palladium-catalyzed cross-coupling reactions (Suzuki, Buchwald-Hartwig), enabling rapid diversification of the carbon skeleton. This makes the compound a strategic building block for structure–activity relationship (SAR) studies targeting kinase inhibitors, anti-infective agents, and CNS-active compounds.

In agrochemical research, β-ketoesters with chloro-aryl substitution have been explored as intermediates in the synthesis of herbicides and fungicides, reflecting the compound's broad utility across research disciplines.

Handling, Storage, and Safety Considerations

As with most aromatic chloro-compounds and β-ketoesters, Methyl 3-(3-chlorophenyl)-3-oxopropanoate should be handled with appropriate personal protective equipment including nitrile gloves, safety glasses, and a laboratory coat. Work should be conducted in a well-ventilated fume hood to avoid inhalation of vapors or aerosols.

The compound should be stored in a tightly sealed container, protected from moisture and direct light, at cool room temperature or refrigerated conditions (2–8 °C is typical for β-ketoesters) to minimize hydrolysis of the ester functionality and degradation of the active methylene moiety. Compatibility with oxidizing agents, strong bases, and strong acids should be avoided.

Users should consult the Safety Data Sheet (SDS) provided with SKU M700284 for complete hazard classifications, first-aid measures, and disposal guidance in accordance with local regulations. Specific GHS hazard codes and pictograms should be verified from the official SDS document.

Frequently asked questions

What is the molecular weight of Methyl 3-(3-chlorophenyl)-3-oxopropanoate?

The molecular weight of Methyl 3-(3-chlorophenyl)-3-oxopropanoate (C₁₀H₉ClO₃) is approximately 212.63 g/mol. This value is derived from its molecular formula and should be confirmed on the certificate of analysis for SKU M700284.

How should Methyl 3-(3-chlorophenyl)-3-oxopropanoate be stored to maintain stability?

This β-ketoester should be stored in a tightly closed container away from moisture and light, ideally at 2–8 °C. Proper storage prevents ester hydrolysis and decomposition of the active methylene group. Consult the SDS for SKU M700284 for full storage requirements.

What are the main synthetic applications of Methyl 3-(3-chlorophenyl)-3-oxopropanoate?

This compound is primarily used as a building block for heterocyclic synthesis, including the preparation of pyrazoles, pyrimidines, and dihydropyridines via condensation reactions at its active methylene site. Its 3-chlorophenyl group also enables palladium-catalyzed cross-coupling diversification, making it valuable in pharmaceutical and agrochemical research.

Can the chloro group in this compound be used for cross-coupling reactions?

Yes, the aryl chloride on the 3-chlorophenyl ring is a viable electrophilic partner in palladium-catalyzed cross-coupling reactions such as Suzuki-Miyaura and Buchwald-Hartwig amination, allowing researchers to diversify the molecular scaffold. Optimization of catalyst, ligand, and base is typically required for aryl chloride substrates.

References

1. March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 4th ed. Wiley-Interscience, 1992. (General reference for Claisen condensation and β-ketoester chemistry.)
2. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed. Oxford University Press, 2012. (Reference for active methylene chemistry and heterocyclic synthesis.)
3. Aladdin Scientific. Product page for Methyl 3-(3-chlorophenyl)-3-oxopropanoate, SKU M700284.

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