4-Acetyl-2-methylpyridine: Properties, Uses & Lab Guide

4-Acetyl-2-methylpyridine is a bifunctional pyridine building block bearing both a methyl group at the 2-position and an acetyl ketone at the 4-position, making it a versatile intermediate in heterocyclic and pharmaceutical synthesis.

IUPAC Name

1-(2-methylpyridin-4-yl)ethan-1-one

CAS Number

6832-16-2

Molecular Formula

C₈H₉NO

Molecular Weight

135.16 g/mol

Functional Groups

Pyridine ring, methyl (C-2), acetyl ketone (C-4)

Aladdin SKU

A183357

Chemical Structure and Key Properties

4-Acetyl-2-methylpyridine (CAS 6832-16-2) is an aromatic heterocyclic compound with the molecular formula C₈H₉NO and a molecular weight of 135.16 g/mol. Its structure consists of a pyridine ring substituted at the 2-position with a methyl group and at the 4-position with an acetyl (COCH₃) group. This combination creates two distinct reactive sites: the electron-withdrawing pyridine nitrogen and the electrophilic carbonyl carbon of the ketone.

The compound is typically encountered as a pale yellow to yellow liquid or low-melting solid. The pyridine nitrogen confers moderate basicity (pKa of conjugate acid approximately 3–4, consistent with 4-substituted pyridines), while the ketone functionality enables nucleophilic addition, condensation, and enolization reactions. The methyl group at C-2 introduces steric influence on the ring nitrogen coordination chemistry, which is exploited in ligand design.

Applications in Organic and Pharmaceutical Synthesis

The dual functionality of 4-Acetyl-2-methylpyridine makes it a valuable building block in multiple synthetic contexts:

• Heterocyclic synthesis: The active methylene adjacent to the carbonyl, combined with the pyridine nitrogen, enables Knoevenagel condensations, aldol reactions, and cyclizations to produce fused heterocyclic scaffolds such as pyrimidines, pyrazoles, and dihydropyridines.
• Pharmaceutical intermediates: Substituted acetylpyridines serve as precursors to biologically active compounds; the 2-methyl group can modulate pharmacokinetic properties and receptor binding selectivity.
• Coordination chemistry and ligand design: The pyridine nitrogen combined with the ketone oxygen offers bidentate coordination potential, facilitating the preparation of metal complexes used in catalysis and materials science.
• Agrochemical research: Acetylpyridine derivatives have been explored as intermediates toward fungicidal and herbicidal agents.

Researchers should select reaction conditions (base, solvent, temperature) appropriate to the target transformation, since the pyridine ring can itself coordinate to Lewis acidic catalysts and influence reaction outcomes.

Handling, Storage, and Safety Guidelines

As with most reactive aromatic carbonyl compounds, appropriate precautions should be observed when working with 4-Acetyl-2-methylpyridine:

• Personal Protective Equipment (PPE): Wear chemically resistant gloves, safety goggles, and a laboratory coat. Use in a well-ventilated fume hood to avoid inhalation of vapors.
• Storage: Store in a tightly sealed container under cool, dry, and dark conditions, away from strong oxidizers, acids, and bases. Refrigerated storage (2–8 °C) is recommended to maintain purity and prevent degradation.
• Spill management: In the event of a spill, absorb with inert material (e.g., dry sand or vermiculite) and dispose of according to local regulations for organic chemical waste.
• First aid: In case of skin or eye contact, flush immediately with copious water and seek medical attention. Consult the Safety Data Sheet (SDS) supplied with the product for full hazard information.

Always consult the product-specific SDS before use. Regulatory classification and exact hazard statements may vary by jurisdiction; verify compliance with local chemical safety legislation.

Analytical Characterization and Purity Verification

Confirming the identity and purity of 4-Acetyl-2-methylpyridine before use is essential for reproducible results. The following analytical methods are commonly applied:

• ¹H NMR spectroscopy: Characteristic signals include the aromatic protons of the pyridine ring (δ ~8.5 ppm for H-3 and H-5), the methyl singlet at C-2 (δ ~2.6 ppm), and the acetyl methyl group (δ ~2.6 ppm). Exact shifts should be confirmed against a reference spectrum in an appropriate deuterated solvent such as CDCl₃.
• GC or HPLC purity analysis: Gas chromatography (GC) with FID detection or reversed-phase HPLC provides quantitative purity assessment. Purity ≥98% is typically required for sensitive synthetic applications.
• IR spectroscopy: A strong carbonyl (C=O) stretch near 1680–1700 cm⁻¹ confirms the ketone functionality; aromatic C=N and C=C stretches appear in the 1580–1600 cm⁻¹ region.
• Mass spectrometry: The expected molecular ion [M+H]⁺ at m/z 136 (ESI-MS) or M⁺ at m/z 135 (EI-MS) confirms the molecular weight.

Batch-specific certificates of analysis (CoA) are available from Aladdin Scientific and should be reviewed to verify lot purity prior to use.

Frequently asked questions

What is the CAS number for 4-Acetyl-2-methylpyridine?

The CAS registry number for 4-Acetyl-2-methylpyridine is 6832-16-2. Aladdin Scientific supplies this compound under SKU A183357.

How should 4-Acetyl-2-methylpyridine be stored to maintain purity?

Store the compound in a tightly sealed container under cool (ideally 2–8 °C), dry, and dark conditions, away from moisture, strong acids, bases, and oxidizers. Always re-seal the container promptly after use to minimise exposure to air and humidity.

What types of reactions can 4-Acetyl-2-methylpyridine undergo in synthesis?

The compound can participate in a range of reactions including Knoevenagel condensations, aldol-type reactions, enolization-mediated alkylations, and cyclizations to form fused heterocycles. Its pyridine nitrogen also enables coordination to metal centres, supporting its use in ligand and complex synthesis.

Is 4-Acetyl-2-methylpyridine suitable for use as a bidentate ligand precursor?

Yes, the combination of the pyridine nitrogen lone pair and the carbonyl oxygen provides two potential donor atoms, making this compound a useful precursor for bidentate N,O-donor ligands in transition-metal coordination chemistry. The 2-methyl substituent can influence the steric environment around the coordinated metal centre.

Where can I find the Safety Data Sheet (SDS) for this product?

The Safety Data Sheet for 4-Acetyl-2-methylpyridine (SKU A183357) is available on the Aladdin Scientific website product page. Always consult the SDS before handling the compound to understand all relevant hazard, storage, and disposal information.

References

1. CAS Common Chemistry. CAS RN 6832-16-2: 1-(2-methylpyridin-4-yl)ethan-1-one. American Chemical Society.
2. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012. Chapters on heterocyclic chemistry and carbonyl reactivity.
3. Aladdin Scientific Product Page: 4-Acetyl-2-methylpyridine, SKU A183357.

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