Butyl Cyanoacetate: Properties, Uses & Lab Guide

Butyl Cyanoacetate is a reactive active-methylene ester widely employed in organic synthesis as a versatile building block for condensation reactions, heterocycle formation, and pharmaceutical intermediate preparation.

CAS Number

5459-58-5

Molecular Formula

C7H11NO2

Molecular Weight

141.17 g/mol

Appearance

Colorless to pale yellow liquid

Key Functional Groups

Nitrile (–CN) and ester (–COO–) flanking an active methylene (–CH2–)

Primary Application

Knoevenagel condensation, synthesis of heterocycles and pharmaceutical intermediates

Chemical Properties and Structure

Butyl Cyanoacetate (CAS 5459-58-5) is the n-butyl ester of cyanoacetic acid, with the molecular formula C₇H₁₁NO₂ and a molecular weight of approximately 141.17 g/mol. Its structure features a central active methylene group (–CH₂–) flanked by two strong electron-withdrawing groups: a nitrile (–CN) and an ester carbonyl (–COO–). This arrangement dramatically lowers the pK_a of the methylene protons, making them highly acidic and readily abstracted by mild bases. The compound is a colorless to pale yellow liquid at room temperature with moderate viscosity. It is miscible with common organic solvents such as ethanol, acetone, and dichloromethane, but has limited miscibility with water. The electron-withdrawing groups confer substantial electrophilic reactivity at the methylene carbon and nucleophilic character at the carbanion formed upon deprotonation.

Applications in Organic Synthesis

Butyl Cyanoacetate is a cornerstone reagent in synthetic organic chemistry, prized for the high reactivity of its active methylene group. Key applications include:

• Knoevenagel Condensation: The reagent undergoes facile Knoevenagel condensation with aldehydes and ketones in the presence of mild amine bases (e.g., piperidine, ammonium acetate) to afford alkylidene cyanoacetates, which are valuable intermediates for further transformations.
• Heterocycle Synthesis: Butyl cyanoacetate serves as a C–C and C–N bond-forming partner in the construction of pyridines, pyrimidines, thiophenes, and other nitrogen- or sulfur-containing heterocycles widely encountered in medicinal chemistry.
• Michael Addition: As an active methylene donor, it participates in 1,4-addition reactions with Michael acceptors such as α,β-unsaturated carbonyl compounds, providing β-substituted products with two orthogonal handles (CN and ester) for further elaboration.
• Pharmaceutical Intermediate Synthesis: The compound is employed in the preparation of drug scaffolds, dye intermediates, and agrochemical precursors, where the nitrile group can be further hydrolyzed, reduced, or cyclized.

Handling, Storage, and Safety

Proper handling and storage of Butyl Cyanoacetate are essential to maintain reagent integrity and ensure laboratory safety.

Storage: Store in a tightly sealed container in a cool, dry, well-ventilated area away from heat sources, ignition sources, and incompatible materials such as strong oxidizers and strong bases. Refrigerated storage (2–8 °C) is recommended for long-term stability. Keep the container under an inert atmosphere (nitrogen or argon) after opening to prevent moisture ingress and hydrolysis of the ester group.

Personal Protective Equipment (PPE): Use appropriate chemical-resistant gloves, safety goggles, and a laboratory coat when handling this reagent. Work in a well-ventilated fume hood to avoid inhalation of vapors, as the nitrile functionality may present inhalation hazards.

Disposal: Dispose of waste material in accordance with local, regional, and national regulations for organic nitrile-containing solvents. Do not pour down the drain.

Note: Always consult the current Safety Data Sheet (SDS) provided by Aladdin Scientific before use for up-to-date hazard classifications, first-aid measures, and regulatory information.

Purity, Specifications, and Quality

For research applications, reagent purity is critical to reproducible outcomes. Aladdin Scientific supplies Butyl Cyanoacetate (SKU: B133488) with defined purity specifications suitable for synthetic and analytical use. Researchers should verify the following parameters when selecting a lot:

• Purity: Confirm the stated purity by certificate of analysis (CoA), typically assessed by GC or HPLC.
• Water Content: Low water content is important, particularly for reactions sensitive to protic impurities; check Karl Fischer titration data if available.
• Color and Appearance: Acceptable lots appear colorless to pale yellow; significant discoloration may indicate degradation or oxidation.
• Lot Traceability: Aladdin Scientific provides lot-specific CoAs to support reproducibility and regulatory documentation in both academic and industrial settings.

Contact Aladdin Scientific technical support for bulk quantities, custom purity grades, or specific analytical data requirements.

Frequently asked questions

What makes Butyl Cyanoacetate useful as an active methylene compound?

Butyl Cyanoacetate contains a methylene group flanked by both a nitrile and an ester group. These two electron-withdrawing substituents synergistically acidify the C–H bonds, allowing easy deprotonation by mild bases and generating a stabilized carbanion that serves as a versatile nucleophile in condensation, Michael addition, and cyclization reactions.

How should Butyl Cyanoacetate be stored to maximize shelf life?

Store Butyl Cyanoacetate in a tightly sealed container under an inert atmosphere (nitrogen or argon) at 2–8 °C, away from moisture, strong oxidizers, and strong bases. Avoiding repeated freeze-thaw cycles and minimizing exposure to air and light will help preserve purity over time.

Which reactions commonly use Butyl Cyanoacetate as a key reagent?

Butyl Cyanoacetate is most commonly used in Knoevenagel condensations with aldehydes or ketones, Michael additions to α,β-unsaturated compounds, and cyclocondensation reactions for the synthesis of heterocyclic scaffolds such as pyridines and pyrimidines. It is also a key building block for pharmaceutical and agrochemical intermediates.

What is the difference between Butyl Cyanoacetate and Ethyl Cyanoacetate?

Both are active methylene cyanoacetate esters with similar reactivity profiles; the key difference is the alkyl chain on the ester—ethyl versus n-butyl. The longer butyl chain increases lipophilicity and may influence solubility and reaction kinetics in certain systems. The choice between them is often guided by the desired properties of the target product or downstream transformation.

References

1. March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 4th ed.; Wiley-Interscience: New York, 1992. (General reference for active methylene chemistry and Knoevenagel condensation.)
2. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012. (Textbook-level discussion of Michael additions and condensation reactions.)
3. Aladdin Scientific. Product Data Sheet: Butyl Cyanoacetate, SKU B133488. (Accessed via Aladdin Scientific official website.)

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