6-Chloropyridazin-3-ol
[CAS# 19064-67-6]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyridazine
• Name: 6-Chloropyridazin-3-ol
• Synonyms: 3-Chloro-6-hydroxypyridazine
• Molecular Formula: C₄H₃ClN₂O
• Molecular Weight: 130.53
• CAS Registry Number: 19064-67-6
• EC Number: 678-370-3
• SMILES: C1=CC(=NNC1=O)Cl

Properties

• Density: 1.5±0.1 g/cm³ Calc.^*
• Melting point: 142 °C (Expl.)
• Boiling point: 350.3±22.0 °C 760 mmHg (Calc.)^*
• Flash point: 165.6±22.3 °C (Calc.)^*
• Index of refraction: 1.593 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Eye irritation	Eye Irrit.	2A	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335

Discovery and Applications

6-Chloropyridazin-3-ol is a halogenated heterocyclic compound consisting of a pyridazine ring substituted with a chlorine atom at position 6 and a hydroxy group at position 3. Its molecular formula is C₄H₃ClN₂O, with a molecular weight of approximately 128.53 g/mol. The pyridazine ring is a six-membered aromatic heterocycle containing two nitrogen atoms at positions 1 and 2, which contribute to the electron density and chemical reactivity of the ring. The hydroxy and chloro substituents confer distinct chemical properties and sites for further functionalization.

Synthesis of 6-chloropyridazin-3-ol typically begins with a pyridazinone or dihydropyridazine precursor. Electrophilic chlorination at position 6 can be carried out using reagents such as N-chlorosuccinimide under controlled conditions to avoid over-halogenation or side reactions. Alternatively, chlorination may be introduced earlier in the synthetic sequence using a pre-chlorinated starting material, followed by hydroxylation at position 3. Hydroxylation can be achieved via selective oxidation or substitution reactions, ensuring the hydroxyl group is installed with correct regioselectivity. Protective groups may be used to control reactivity during multi-step syntheses.

The hydroxy group at position 3 makes the compound nucleophilic and able to participate in hydrogen bonding, increasing its polarity and solubility in polar solvents. The chlorine atom at position 6 serves as both an electron-withdrawing group, stabilizing the ring system, and as a reactive site for further substitution reactions. Halogen atoms such as chlorine can undergo palladium-catalyzed cross-coupling reactions, nucleophilic aromatic substitution, or metalation to introduce other substituents, providing a versatile handle for derivatization.

Chemically, 6-chloropyridazin-3-ol exhibits moderate stability under ambient conditions. It is generally a solid at room temperature, with solubility in polar organic solvents such as ethanol, acetone, or dimethyl sulfoxide. The hydroxy group may be deprotonated under basic conditions, forming salts or participating in esterification reactions. The chlorine substituent is relatively inert under neutral conditions but can undergo substitution in the presence of strong nucleophiles or under catalytic conditions, allowing chemists to introduce new functional groups selectively.

In practical applications, 6-chloropyridazin-3-ol is primarily used as an intermediate in the synthesis of heterocyclic compounds with potential biological activity. Its functional groups allow for the preparation of derivatives that can serve as enzyme inhibitors, agrochemical candidates, or pharmaceutical intermediates. The fused electron-rich and electron-deficient regions of the ring system facilitate interactions with target proteins, while the hydroxy and chloro groups enable modifications to tune solubility, reactivity, and binding properties.

In addition to its role in chemical synthesis, the compound’s structural features make it a useful building block for medicinal chemistry. The pyridazine core is commonly found in biologically active compounds, and the substitution pattern of 6-chloropyridazin-3-ol allows for systematic exploration of structure–activity relationships. By modifying the hydroxy or chloro groups or introducing additional substituents, researchers can create analogs with varied electronic, steric, and hydrogen-bonding properties, supporting the development of novel heterocyclic molecules with specific biological effects.

References

2023. Multimodal action of KRP203 on phosphoinositide kinases in vitro and in cells. Biochemical and Biophysical Research Communications.
DOI: 10.1016/j.bbrc.2023.08.050

2022. A quantitative high-throughput screen identifies compounds that lower expression of the SCA2-and ALS-associated gene ATXN2. Journal of Biological Chemistry.
DOI: 10.1016/j.jbc.2022.102228

2018. Diverse Biologically Active Pyridazine Analogs: A Scaffold for the Highly Functionalized Heterocyclic Compounds. Reviews and Advances in Chemistry.
DOI: 10.1134/s2079978018030019