2,6-Dihydroxy-3-cyanopyridine: Properties, Handling & Lab Use

2,6-Dihydroxy-3-cyanopyridine is a bifunctional heterocyclic building block bearing both hydroxyl and nitrile substituents on the pyridine ring, making it a versatile intermediate in pharmaceutical and agrochemical synthesis.

IUPAC Name

2,6-dihydroxypyridine-3-carbonitrile

Molecular Formula

C6H4N2O2

Molecular Weight

136.11 g/mol

SKU

D192953

Functional Groups

Hydroxyl (–OH) at positions 2 and 6; nitrile (–CN) at position 3

Tautomeric Form

Exists predominantly in the dihydroxypyridine/pyridinedione tautomeric form in solid state

Chemical Identity and Structural Features

2,6-Dihydroxy-3-cyanopyridine (CAS registry number to be confirmed; SKU D192953) is a substituted pyridine in which hydroxyl groups occupy the 2- and 6-positions of the ring and a nitrile group is located at the 3-position. The compound participates in a well-known tautomeric equilibrium between the aromatic 2,6-dihydroxypyridine form and the non-aromatic 2,6-dioxo (pyridinedione) form; in the solid state the dioxo tautomer is often predominant, while the distribution may shift in solution depending on solvent polarity and pH.

The presence of the electron-withdrawing nitrile group adjacent to one of the ring nitrogen-flanking hydroxyls modulates the electron density of the ring, influencing both the acidity of the hydroxyl groups and the reactivity of the nitrile toward nucleophiles such as amines and hydroxylamine. This combination of reactive handles makes the compound a useful scaffold for constructing more complex heterocyclic architectures including oxazolopyridines, aminocyanopyridines, and related fused-ring systems.

Research Applications and Synthetic Utility

In medicinal chemistry, 2,6-dihydroxy-3-cyanopyridine serves as a key intermediate for the preparation of bioactive heterocycles. The nitrile group can be converted to amidines, tetrazoles, amides, or primary amines under appropriate conditions, enabling rapid diversification of the core scaffold. Condensation of the 2,6-dioxo form with bifunctional reagents such as phosphorus oxychloride or thionyl chloride yields 2,6-dichloropyridine-3-carbonitrile, a highly activated electrophile widely used in nucleophilic aromatic substitution (SNAr) reactions.

In agrochemical research, related cyanopyridine scaffolds feature prominently in herbicide and fungicide design; 2,6-dihydroxy-3-cyanopyridine may thus serve as a precursor to such compounds. It has also been investigated as a ligand precursor and coordination compound building block in inorganic and supramolecular chemistry, where its multiple donor atoms (ring nitrogen, oxygen, and nitrile nitrogen) can coordinate to transition metals.

Additionally, the compound is of interest in the synthesis of fluorescent dyes and optical materials owing to the electron-deficient aromatic system created by the combined nitrile and carbonyl (dioxo tautomer) substituents.

Handling, Storage and Safety Guidelines

Personal Protective Equipment (PPE): Handle 2,6-dihydroxy-3-cyanopyridine wearing appropriate chemical-resistant gloves (nitrile recommended), a laboratory coat, and safety goggles. Because the compound contains a nitrile group, exercise caution regarding potential liberation of cyanide-containing species under strongly acidic or strongly basic aqueous conditions or upon thermal decomposition; work in a well-ventilated fume hood.

Storage: Store the reagent in a tightly sealed container in a cool, dry location away from strong acids, strong bases, and oxidizing agents. Recommended storage temperature is 2–8 °C or room temperature as specified on the product label; confirm conditions on the Certificate of Analysis (CoA) supplied with each lot. Protect from light and moisture to prevent hydrolysis of the nitrile group.

Disposal: Dispose of waste material in accordance with local, regional, and national regulations for nitrile-containing organic compounds. Do not pour down the drain. Consult your institution's Environmental Health and Safety (EHS) office for guidance.

First Aid: In case of skin or eye contact, rinse immediately with copious amounts of water for at least 15 minutes and seek medical attention. If inhaled, move to fresh air. Consult the Safety Data Sheet (SDS) for complete hazard and first-aid information before use.

Purity, Quality and Supplier Information

Aladdin Scientific supplies 2,6-dihydroxy-3-cyanopyridine under SKU D192953. Each lot is accompanied by a Certificate of Analysis (CoA) detailing purity (typically assessed by HPLC or titration), appearance, melting point, and other quality attributes. Researchers should verify purity specifications against their application requirements before use; synthetic applications demanding high selectivity may require reagent of ≥98% purity.

Lot-specific CoAs can be requested from Aladdin Scientific customer service or downloaded via the product page on the Aladdin website. For regulatory or GMP-adjacent applications, contact Aladdin Scientific to discuss documentation availability and custom quality requirements.

Frequently asked questions

What tautomeric form does 2,6-Dihydroxy-3-cyanopyridine adopt in solution?

2,6-Dihydroxy-3-cyanopyridine exists in a tautomeric equilibrium between the 2,6-dihydroxy (aromatic) and 2,6-dioxo (lactam) forms. The predominant tautomer in solution depends on solvent polarity and pH; polar protic solvents and neutral-to-basic conditions tend to favor the aromatic dihydroxy form, while the dioxo form may dominate in the solid state. NMR or UV-Vis analysis in your specific solvent system is recommended for confirmation.

How should I convert 2,6-Dihydroxy-3-cyanopyridine to the corresponding 2,6-dichloropyridine-3-carbonitrile?

The standard approach is treatment with phosphorus oxychloride (POCl3), optionally in the presence of a tertiary amine base such as triethylamine or N,N-dimethylaniline as an acid scavenger, under reflux conditions. The resulting 2,6-dichloropyridine-3-carbonitrile is an activated electrophile suitable for SNAr reactions with nitrogen, oxygen, or sulfur nucleophiles. Exact reaction conditions (stoichiometry, temperature, and solvent) should be optimized for your substrate; consult primary literature for validated procedures.

What solvents are recommended for dissolving 2,6-Dihydroxy-3-cyanopyridine?

Polar aprotic solvents such as dimethyl sulfoxide (DMSO) and N,N-dimethylformamide (DMF) generally dissolve 2,6-dihydroxy-3-cyanopyridine well. Polar protic solvents such as methanol or ethanol may also be used. The compound has limited solubility in non-polar solvents such as hexane or diethyl ether. Always verify solubility under your specific experimental conditions, and note that basic aqueous conditions can promote ionization and improve aqueous solubility.

Is 2,6-Dihydroxy-3-cyanopyridine stable to aqueous conditions?

The compound is generally stable under mild, neutral aqueous conditions. However, prolonged exposure to strongly acidic or strongly basic aqueous environments can promote hydrolysis of the nitrile group to the corresponding amide or carboxylic acid. For maximum stability, store the solid reagent dry and use freshly prepared solutions when performing sensitive reactions.

References

1. General reference on tautomerism of 2-hydroxypyridine and related compounds — textbook-level knowledge; no specific DOI available.
2. Synthesis of 2,6-dichloropyridine-3-carbonitrile via POCl3 chlorination — standard synthetic procedure referenced in primary literature; specific citation to be identified.
3. Aladdin Scientific product page for 2,6-Dihydroxy-3-cyanopyridine, SKU D192953.

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