6-Cyclopropylnicotinic Acid: Properties, Handling & Lab Use

6-Cyclopropylnicotinic acid is a pyridine-2-carboxylic acid derivative bearing a cyclopropyl substituent at the 6-position, widely valued as a versatile heterocyclic building block in medicinal chemistry and pharmaceutical synthesis.

IUPAC Name

6-cyclopropylpyridine-3-carboxylic acid

Molecular Formula

C₉H₉NO₂

Molecular Weight

163.17 g/mol

CAS Number

1060806-36-1

SKU / Product Code

C194934

Functional Groups

Carboxylic acid (–COOH), pyridine ring, cyclopropyl group

Recommended Storage

Cool, dry place; sealed container; away from light and moisture

Chemical Identity and Structure

6-Cyclopropylnicotinic acid (SKU: C194934) is a substituted pyridinecarboxylic acid in which the nicotinic acid (pyridine-3-carboxylic acid) scaffold carries a cyclopropyl ring at the 6-position of the pyridine. Its molecular formula is C₉H₉NO₂ with a molecular weight of approximately 163.17 g/mol.

The compound combines three pharmacophoric elements of synthetic relevance: (1) the electron-deficient pyridine nitrogen, which modulates acidity and hydrogen-bond-acceptor character; (2) the free carboxylic acid at the 3-position, enabling amide coupling, esterification, and salt formation; and (3) the strained cyclopropyl group at the 6-position, which donates electron density through hyperconjugation and is well known to improve metabolic stability and lipophilicity tuning in drug candidates.

The combination of these features makes 6-cyclopropylnicotinic acid a sought-after fragment for structure–activity relationship (SAR) studies and for the construction of more complex heterocyclic architectures.

Physicochemical Properties and Spectral Characteristics

6-Cyclopropylnicotinic acid is typically isolated as a white to off-white crystalline solid. Key physicochemical properties expected for this class of compound include:

• Appearance: White to off-white powder or crystals.
• Solubility: Moderately soluble in polar aprotic solvents such as DMSO and DMF; sparingly soluble in water at neutral pH but solubility increases significantly under basic conditions due to carboxylate formation. Limited solubility in non-polar organic solvents.
• pKa: The carboxylic acid pKa is expected to be in the range typical for electron-deficient aryl/heteroarylcarboxylic acids (approximately 3–5); exact value should be confirmed experimentally.
• LogP: The cyclopropyl substituent contributes modest lipophilicity; predicted cLogP values for this scaffold are generally low-to-moderate, supporting aqueous formulation in buffered systems.

Infrared spectroscopy will show a broad O–H stretch around 2500–3300 cm⁻¹ overlapping C–H stretches, a strong carbonyl (C=O) stretch near 1680–1720 cm⁻¹, and aromatic C=N and C=C ring stretches. ¹H NMR (400 MHz, DMSO-d₆) is expected to display characteristic aromatic proton signals for the pyridine ring and a multiplet for the cyclopropyl methine proton, along with the broad carboxylic acid OH signal.

Note: Specific melting point, exact pKa, and detailed spectral data should be verified against the certificate of analysis (CoA) supplied with C194934.

Synthetic Applications and Research Use

6-Cyclopropylnicotinic acid serves as a valuable building block in several classes of synthetic transformations relevant to drug discovery and materials science:

1. Amide Bond Formation

The carboxylic acid functionality readily undergoes coupling with primary and secondary amines using standard peptide-coupling reagents (e.g., HATU, EDC/HOBt, T3P) to yield nicotinamide derivatives. Such amides are prominent scaffolds in kinase inhibitor and GPCR modulator research.

2. Esterification

Reaction with alcohols under acid catalysis or via activated intermediates (acid chlorides, mixed anhydrides) affords esters suitable as prodrug motifs or protected intermediates for further elaboration.

3. Metal-Catalyzed Cross-Coupling

Although the carboxylic acid itself is not a direct cross-coupling partner, conversion to the corresponding boronic ester, triflate (via reduction to alcohol then triflation), or use of decarboxylative coupling protocols enables entry into C–C bond-forming chemistry. The pyridine ring can also coordinate to palladium or other transition metals, directing C–H functionalization.

4. Salt Formation and Coordination Chemistry

The pyridine nitrogen and carboxylate anion together create a bidentate ligand motif of interest for the preparation of metal–organic frameworks (MOFs) and coordination polymers.

Researchers are encouraged to optimize reaction conditions for specific transformations with reference to literature precedents for structurally analogous nicotinic acid derivatives.

Safe Handling, Storage, and Disposal

Although 6-cyclopropylnicotinic acid is not classified as a highly hazardous substance, standard laboratory safety practices apply:

Personal Protective Equipment (PPE)

• Wear appropriate chemical-resistant gloves (e.g., nitrile) when handling the solid or solutions.
• Use safety glasses or goggles to protect against dust or splashing.
• A laboratory coat or protective clothing should be worn at all times.
• Handle fine powders in a well-ventilated area or chemical fume hood to avoid inhalation of dust.

Storage Conditions

• Store in a tightly sealed container in a cool (15–25 °C), dry location away from direct light and moisture.
• Keep away from strong oxidizers, bases, and reactive amines to prevent unintended reactions.
• Consult the Safety Data Sheet (SDS) supplied with C194934 for specific hazard classifications and first-aid measures.

Disposal

• Dispose of waste material and solutions in accordance with local, regional, and national regulations for chemical waste.
• Do not pour down drains without verifying compliance with local waste-water treatment regulations.

Always consult the current SDS for C194934 before use. Hazard classification data provided here is general and should not substitute official documentation.

Quality, Purity, and Ordering Information

Aladdin Scientific supplies 6-cyclopropylnicotinic acid under product code C194934. Key quality considerations for research use include:

Purity and Analysis

• Each lot is accompanied by a Certificate of Analysis (CoA) detailing purity (typically assessed by HPLC or NMR), appearance, and identity confirmation (by NMR and/or MS).
• Researchers requiring high purity (≥98%) for sensitive biological assays or reference standard applications should confirm lot-specific purity from the CoA prior to use.

Available Quantities

• Contact Aladdin Scientific or visit the product page for current available pack sizes and pricing. Custom quantities may be available upon request.

Ordering

• Orders can be placed online via the Aladdin Scientific website using SKU C194934, or by contacting your regional Aladdin representative.
• For bulk or custom synthesis enquiries, please contact technical support.

Shipping and Storage on Receipt

• Products are shipped at ambient temperature unless otherwise specified. Upon receipt, inspect the container for integrity and store immediately under the recommended conditions (cool, dry, sealed).
• If the product has been exposed to moisture or elevated temperature during transit, contact Aladdin Scientific customer service before use.

Frequently asked questions

What is 6-cyclopropylnicotinic acid used for in research?

6-Cyclopropylnicotinic acid (C194934) is primarily used as a heterocyclic building block in medicinal chemistry and drug discovery. Its carboxylic acid group facilitates amide coupling and esterification reactions, while the cyclopropyl substituent is valued for improving the metabolic stability and lipophilicity profile of drug candidates. It is also of interest for coordination chemistry and MOF synthesis.

How should 6-cyclopropylnicotinic acid be stored to maintain stability?

Store 6-cyclopropylnicotinic acid in a tightly sealed container at room temperature (15–25 °C) in a cool, dry location away from direct light and moisture. Avoid contact with strong oxidizers, strong bases, and reactive amines. Always refer to the product's Safety Data Sheet (SDS) and Certificate of Analysis (CoA) for lot-specific guidance.

What solvents are suitable for dissolving 6-cyclopropylnicotinic acid?

6-Cyclopropylnicotinic acid is moderately soluble in polar aprotic solvents such as DMSO and DMF, which are commonly used for stock solution preparation. Aqueous solubility is low at neutral pH but increases under basic conditions (e.g., dilute NaOH or phosphate buffer at pH >7) due to carboxylate formation. Solubility in non-polar solvents such as hexane or diethyl ether is generally low.

How do I confirm the identity and purity of the received product?

Each batch of C194934 is supplied with a Certificate of Analysis (CoA) that includes identity confirmation (typically by NMR and/or mass spectrometry) and purity data (typically by HPLC). Customers should review the CoA upon receipt and contact Aladdin Scientific customer service if the results do not meet their specifications.

Can 6-cyclopropylnicotinic acid be used directly in amide coupling reactions?

Yes. The free carboxylic acid of 6-cyclopropylnicotinic acid can be directly activated using standard coupling reagents such as HATU, EDC/HOBt, or T3P in the presence of a suitable amine and base (e.g., DIPEA or triethylamine) in polar aprotic solvents. Reaction conditions should be optimized for the specific amine coupling partner and desired product.

References

1. March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure. Wiley-Interscience. General reference for carboxylic acid transformations including amide coupling and esterification.
2. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry. Oxford University Press. Reference for heterocyclic chemistry and pyridine reactivity.
3. Taylor, R. D.; MacCoss, M.; Lawson, A. D. G. Rings in Drugs. J. Med. Chem. 2014, 57, 5845–5859. General reference for cyclopropyl group use in drug design. doi:10.1021/jm4017625
4. Aladdin Scientific. Product Certificate of Analysis for 6-Cyclopropylnicotinic acid, SKU C194934. Available from Aladdin Scientific upon product purchase.

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