Ethyl 4-Pyrazolecarboxylate: Properties, Uses & Lab Guide

Ethyl 4-pyrazolecarboxylate is a synthetically versatile heterocyclic ester widely employed as a core building block in medicinal chemistry, agrochemical research, and the preparation of pharmacologically active pyrazole-containing compounds.

CAS Number

37622-90-5

Molecular Formula

C6H8N2O2

Molecular Weight

140.14 g/mol

Appearance

White to off-white crystalline solid

Key Functional Groups

Pyrazole ring (NH), ethyl ester (–COOEt)

Primary Application

Heterocyclic building block for drug discovery and synthesis

Aladdin SKU

E121781

Chemical Identity and Structure

Ethyl 4-pyrazolecarboxylate (CAS 37622-90-5) is the ethyl ester of pyrazole-4-carboxylic acid. Its molecular formula is C₆H₈N₂O₂ with a molecular weight of 140.14 g/mol. The compound features a five-membered aromatic pyrazole ring bearing two adjacent nitrogen atoms, with an ethyl ester substituent at the 4-position and a free NH at the 1-position.

The presence of the NH tautomer makes this compound an ambident nucleophile: the ring nitrogen can be alkylated or acylated, while the ester group serves as a handle for further functional-group transformations such as hydrolysis, amide coupling, or reduction. This dual reactivity is central to the compound's broad utility in synthetic chemistry.

The compound is typically obtained as a white to off-white crystalline solid and exhibits good stability under ambient conditions when stored in a cool, dry environment away from strong bases and moisture.

Synthetic Applications in Drug Discovery

The pyrazole scaffold is one of the most frequently encountered heterocyclic motifs in approved pharmaceuticals and drug candidates, appearing in compounds targeting kinases, cyclooxygenases, phosphodiesterases, and numerous other enzyme classes. Ethyl 4-pyrazolecarboxylate serves as a direct entry point to this chemical space.

Common transformations applied to this building block include:

• N-alkylation and N-arylation: Reaction with alkyl halides or aryl halides (under copper or palladium catalysis) installs diverse N-substituents, generating N-substituted pyrazole-4-carboxylate libraries.
• Ester hydrolysis: Base- or acid-mediated saponification affords pyrazole-4-carboxylic acid, a key intermediate for subsequent amide-bond formation with amines.
• Amide coupling: Activation of the derived carboxylic acid with coupling reagents (e.g., HATU, EDC) enables introduction of structurally diverse amine fragments, yielding pyrazole-4-carboxamides relevant to kinase inhibitor programs.
• Reduction: DIBAL-H or LiAlH₄ reduction of the ester provides the 4-(hydroxymethyl)pyrazole alcohol, a handle for further elaboration.

These straightforward transformations make Ethyl 4-pyrazolecarboxylate an efficient starting point for parallel synthesis and fragment-based drug discovery campaigns.

Handling, Storage, and Safety

Ethyl 4-pyrazolecarboxylate is considered a low-hazard laboratory reagent under standard handling conditions; however, good laboratory practice should always be observed.

Storage: Store in a tightly sealed container in a cool (2–25 °C), dry, and well-ventilated location, away from incompatible materials such as strong oxidizers and strong bases. Shelf life is generally satisfactory when stored under these conditions; confirm specific expiry information on the certificate of analysis supplied with each lot.

Personal Protective Equipment (PPE): Wear appropriate laboratory coat, chemical-resistant gloves, and safety glasses when handling this compound. Avoid inhalation of dust or vapors.

Waste Disposal: Dispose of waste material in accordance with local, regional, and national regulations governing chemical waste. Do not pour into drains.

Always consult the Safety Data Sheet (SDS) provided by Aladdin Scientific before use. The SDS contains up-to-date information on GHS hazard classifications, first-aid measures, and regulatory compliance data specific to this product lot.

Purity Specifications and Quality Assurance

For reliable results in synthetic and biological applications, reagent purity is critical. Aladdin Scientific's Ethyl 4-pyrazolecarboxylate (SKU E121781) is characterized using standard analytical techniques to ensure consistent lot-to-lot quality.

Typical analytical methods applied to this product include:

• High-Performance Liquid Chromatography (HPLC): Used to determine chemical purity by area normalization; purity specifications are stated on the product certificate of analysis.
• ¹H and ¹³C NMR Spectroscopy: Confirms structural identity and detects residual solvent or synthetic impurities.
• Mass Spectrometry (MS): Verifies molecular weight and fragmentation pattern consistent with the target structure.
• Melting Point: Physical characterization consistent with literature values for the crystalline solid.

Each product lot is supplied with a Certificate of Analysis (CoA) documenting measured purity and analytical data. Researchers requiring custom purity grades or larger quantities are encouraged to contact Aladdin Scientific's technical sales team for bespoke solutions.

Frequently Encountered Reaction Conditions

Researchers working with Ethyl 4-pyrazolecarboxylate will find the compound compatible with a broad range of standard organic solvents and reaction conditions. The following guidelines reflect general laboratory practice for this class of compound:

Solvents: The compound exhibits good solubility in common polar aprotic solvents (DMF, DMSO, acetonitrile) and moderate solubility in ethanol, methanol, and dichloromethane. Solubility in water is limited.

N-functionalization: N-alkylation is typically carried out using K₂CO₃ or Cs₂CO₃ as base in DMF at room temperature to 80 °C. Regioselectivity between N1 and N2 alkylation may depend on the electrophile and reaction conditions; monitoring by TLC or LCMS is recommended.

Ester hydrolysis: LiOH or NaOH (1–2 M aqueous) in THF/MeOH/water mixtures at room temperature typically achieves clean saponification within 1–4 hours.

Compatibility: The compound is generally stable toward mild acids, mild bases, and standard coupling reagent conditions. Prolonged exposure to strong acids or bases should be avoided to prevent ring degradation or undesired hydrolysis.

Frequently asked questions

What is the CAS number for Ethyl 4-pyrazolecarboxylate?

The CAS registry number for Ethyl 4-pyrazolecarboxylate is 37622-90-5. Aladdin Scientific lists this compound under SKU E121781.

How should Ethyl 4-pyrazolecarboxylate be stored to maintain stability?

Store Ethyl 4-pyrazolecarboxylate in a tightly sealed container at cool temperatures (2–25 °C) in a dry, well-ventilated area away from strong oxidizers, strong bases, and moisture. Refer to the product's Certificate of Analysis and Safety Data Sheet for lot-specific recommendations.

What are the main uses of Ethyl 4-pyrazolecarboxylate in research?

Ethyl 4-pyrazolecarboxylate is primarily used as a heterocyclic building block in medicinal chemistry and drug discovery. It can be N-alkylated or N-arylated at the ring nitrogen, hydrolyzed to the corresponding carboxylic acid for amide coupling, or reduced to the hydroxymethyl derivative, enabling the rapid construction of diverse pyrazole-containing compound libraries.

Is Ethyl 4-pyrazolecarboxylate compatible with standard amide coupling reagents?

Yes, once the ester is hydrolyzed to pyrazole-4-carboxylic acid, the resulting acid is compatible with standard amide coupling reagents such as HATU, HBTU, and EDC/HOBt under typical conditions used for heterocyclic carboxylic acids. The ester itself is stable to these reagent systems.

How can I confirm the regioselectivity of N-alkylation on Ethyl 4-pyrazolecarboxylate?

Regioselectivity of N-alkylation (N1 vs N2 substitution) in pyrazoles can be assessed by ¹H NMR spectroscopy, where the chemical shifts and coupling patterns of ring protons differ between the two regioisomers. NOESY experiments or X-ray crystallography may be used for definitive assignment in ambiguous cases.

References

1. Fustero, S.; Sánchez-Roselló, M.; Barrio, P.; Simón-Fuentes, A. From 2000 to Mid-2010: A Fruitful Decade for the Synthesis of Pyrazoles. Chem. Rev. 2011, 111, 6984–7034. doi:10.1021/cr100394t
2. Claramunt, R. M.; López, C.; Elguero, J. The Use of NMR Spectroscopy to Study the Tautomerism and Isomerism of Pyrazoles. ARKIVOC 2006, Part V, 5–15.
3. Elguero, J. Pyrazoles. In Comprehensive Heterocyclic Chemistry II; Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.; Pergamon: Oxford, 1996; Vol. 3, pp 1–75.

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