Ethyl 5-Methylnicotinate: Handling & Laboratory Use Guide

Ethyl 5-methylnicotinate is an ethyl ester derivative of 5-methylnicotinic acid featuring a pyridine ring substituted at the 3-position with an ester group and at the 5-position with a methyl group, widely employed as a versatile building block in medicinal chemistry, heterocyclic synthesis, and pharmaceutical intermediate preparation.

Chemical Name

Ethyl 5-methylnicotinate (Ethyl 5-methylpyridine-3-carboxylate)

Molecular Formula

C9H11NO2

Molecular Weight

165.19 g/mol

Aladdin SKU

E191998

Functional Class

Pyridine carboxylate ester; heterocyclic building block

Recommended Storage

Cool, dry place away from light; sealed container at room temperature unless otherwise specified

Chemical Identity and Properties

Ethyl 5-methylnicotinate (CAS number should be confirmed with the supplier certificate of analysis) is an aromatic heterocyclic ester belonging to the nicotinate family. Its structure consists of a pyridine ring bearing a carboethoxy group at position 3 and a methyl substituent at position 5. The compound typically presents as a colorless to pale-yellow liquid or low-melting solid, with moderate solubility in common organic solvents such as ethanol, dichloromethane, ethyl acetate, and acetone, and limited solubility in water.

The ester functionality renders it susceptible to hydrolysis under strongly acidic or basic aqueous conditions, yielding 5-methylnicotinic acid and ethanol. The electron-withdrawing pyridine nitrogen and ester group collectively modulate the reactivity of the ring toward nucleophilic and electrophilic transformations, making it a useful substrate for further functionalization in multi-step synthetic sequences.

Research Applications

Ethyl 5-methylnicotinate serves as an important synthetic intermediate and building block in several research domains:

• Medicinal Chemistry: The nicotinate scaffold is structurally related to niacin (vitamin B3) and appears in a range of pharmacologically active compounds. Ethyl 5-methylnicotinate can be elaborated into more complex heterocycles through ester hydrolysis, amide coupling, reduction to the corresponding alcohol or aldehyde, and N-alkylation or N-oxidation of the pyridine nitrogen.
• Heterocyclic Synthesis: The compound is used as a precursor in the synthesis of substituted pyridines, naphthyridines, and related fused ring systems. Cross-coupling reactions (e.g., Suzuki, Negishi, Buchwald–Hartwig) can be employed after halogenation of available ring positions.
• Agrochemical Research: Methylnicotinate esters serve as intermediates in the preparation of pyridine-containing agrochemical candidates targeting various biological pathways.
• Material Science: Pyridine-based esters with tunable electronic properties are explored as ligands in coordination chemistry and as components in functional organic materials.

Researchers should verify compatibility of Ethyl 5-methylnicotinate with their specific assay or synthetic conditions prior to large-scale use.

Safe Handling, Storage, and Disposal

Personal Protective Equipment (PPE): When handling Ethyl 5-methylnicotinate, wear appropriate PPE including chemical-resistant gloves (nitrile recommended), laboratory coat, and safety goggles. Work in a well-ventilated fume hood to minimize inhalation of vapors.

Storage: Store in a tightly sealed container in a cool, dry location away from direct light and incompatible materials such as strong oxidizers, strong acids, and strong bases. Unless the product certificate of analysis specifies otherwise, room-temperature storage is generally appropriate. Confirm specific storage conditions from the Aladdin product page and certificate of analysis for each lot.

Stability: The ester bond is susceptible to moisture-promoted hydrolysis over prolonged periods. Ensure containers are resealed promptly after use. Avoid prolonged exposure to atmospheric moisture.

Disposal: Dispose of waste material in accordance with local, regional, and national regulations governing organic solvent and chemical waste. Do not pour down the drain. Consult the Safety Data Sheet (SDS) supplied with the product for jurisdiction-specific disposal guidance.

First Aid: In case of skin or eye contact, flush thoroughly with water for at least 15 minutes and seek medical attention if irritation persists. If inhaled, move to fresh air immediately. Refer to the product SDS for comprehensive first-aid measures.

Quality, Purity, and Analytical Considerations

For research-grade applications, purity is a critical parameter. Aladdin Scientific supplies Ethyl 5-methylnicotinate (SKU: E191998) with purity and specification details documented on the product certificate of analysis (CoA). Researchers should request and review the CoA for each lot received, paying attention to:

• Purity (GC or HPLC): Typical research-grade material is supplied at ≥98% purity; confirm exact specification from the CoA.
• Appearance: Assess the physical state against the CoA description; any unexpected coloration or solidification may indicate degradation.
• NMR/MS confirmation: For critical synthetic applications, in-house verification by ¹H NMR (characteristic aromatic signals for the 3,5-disubstituted pyridine ring, ester CH₂ quartet near δ 4.4 ppm, and methyl singlet) and/or mass spectrometry is recommended.
• Water content: Karl Fischer titration can be used to confirm low moisture levels if hydrolytic sensitivity is a concern in downstream reactions.

Lot-to-lot consistency should be evaluated when the compound is used in reproducibility-sensitive experiments. Contact Aladdin Scientific customer support for custom purity grades or bulk quantities.

Preparation of Common Working Solutions

The following guidelines apply to preparing stock and working solutions of Ethyl 5-methylnicotinate for synthetic or analytical use:

1. Solvent selection: Ethyl 5-methylnicotinate is freely soluble in organic solvents including ethanol, DMSO, dichloromethane, THF, and ethyl acetate. For aqueous-based assays, prepare a concentrated stock in DMSO and dilute into aqueous buffer to the desired final concentration, noting that DMSO content should typically remain below 1% v/v in biological assays to avoid co-solvent effects.
2. Concentration calculation: Use the molecular weight of 165.19 g/mol for accurate molarity calculations. Example: to prepare a 100 mM stock in 10 mL DMSO, dissolve 165.19 mg of the compound in DMSO and bring to 10 mL total volume.
3. Filtration: Filter solutions through a 0.2 µm PTFE membrane syringe filter before use in analytical instruments to remove particulates.
4. Stability of solutions: Prepared solutions should be stored under inert atmosphere (nitrogen or argon) if long-term stability is required, and kept at 2–8 °C or as appropriate for the solvent system used. Avoid repeated freeze-thaw cycles.

All solution preparation should be performed in a fume hood with appropriate PPE.

Frequently asked questions

What is the recommended storage condition for Ethyl 5-methylnicotinate (E191998)?

Ethyl 5-methylnicotinate should be stored in a tightly sealed container in a cool, dry place away from direct light, strong oxidizers, and moisture. Confirm the exact conditions specified on the Aladdin product page and certificate of analysis for your specific lot, as conditions may vary by formulation or purity grade.

In which solvents is Ethyl 5-methylnicotinate soluble?

Ethyl 5-methylnicotinate is soluble in common organic solvents including ethanol, DMSO, dichloromethane, tetrahydrofuran (THF), and ethyl acetate. Its solubility in water is limited due to the lipophilic ester and methyl groups. For aqueous applications, dissolution in DMSO followed by dilution into aqueous buffer is recommended.

What synthetic transformations can be performed on Ethyl 5-methylnicotinate?

Ethyl 5-methylnicotinate can undergo a variety of transformations: (1) saponification or acid-catalyzed hydrolysis to give 5-methylnicotinic acid; (2) aminolysis to yield the corresponding nicotinamide; (3) reduction (e.g., with LiAlH4 or DIBAL-H) to give the 5-methylpyridine-3-methanol; (4) halogenation of the ring for subsequent cross-coupling reactions; and (5) N-oxidation of the pyridine nitrogen. These reactions make it a versatile intermediate for medicinal and synthetic chemistry.

How do I verify the identity and purity of Ethyl 5-methylnicotinate upon receipt?

Upon receipt, review the certificate of analysis (CoA) provided with the product for purity (GC or HPLC), appearance, and other relevant specifications. For additional in-house confirmation, ¹H NMR spectroscopy is recommended: look for characteristic aromatic proton signals corresponding to the 3,5-disubstituted pyridine ring, an ethyl ester quartet near δ 4.4 ppm (CH₂) and a triplet near δ 1.4 ppm (CH₃), and a methyl singlet from the 5-methyl group. Mass spectrometry confirming m/z = 165.08 (M+H for C9H11NO2) provides further identity confirmation.

Is Ethyl 5-methylnicotinate suitable for use in biological assays?

Ethyl 5-methylnicotinate is primarily a synthetic intermediate and building block; its direct biological activity profile should be established empirically by the end user. When used in cell-based or biochemical assays, prepare stocks in DMSO and ensure final DMSO concentrations remain below cytotoxic thresholds (typically ≤0.5–1% v/v). Consult relevant literature and run appropriate vehicle controls.

References

1. March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure. Wiley-Interscience. (General reference for ester hydrolysis and heterocyclic chemistry.)
2. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry. Oxford University Press. (Reference for ester reactions and pyridine functionalization.)
3. Aladdin Scientific. Product Certificate of Analysis: Ethyl 5-methylnicotinate, SKU E191998. (Consult current lot CoA for purity and specification data.)

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