4-Pyridazinecarboxylic acid
[CAS 50681-25-9]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyridazine
• Name: 4-Pyridazinecarboxylic acid
• Synonyms: pyridazine-4-carboxylic acid
• Molecular Formula: C₅H₄N₂O₂
• Molecular Weight: 124.10
• CAS Registry Number: 50681-25-9
• EC Number: 610-561-9
• SMILES: C1=CN=NC=C1C(=O)O

Properties

• Density: 1.4±0.1 g/cm³ Calc.^*
• Melting point: 244.2 °C (Decomposes) (Expl.)
• Boiling point: 404.2±18.0 °C 760 mmHg (Calc.)^*
• Flash point: 198.3±21.2 °C (Calc.)^*
• Index of refraction: 1.579 (Calc.)^*

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

Safety Data

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

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2	H319
Eye irritation	Eye Irrit.	2A	H319
Acute toxicity	Acute Tox.	4	H332
Acute toxicity	Acute Tox.	4	H312
Acute toxicity	Acute Tox.	4	H302

chemBlink Chemical Story

4-Pyridazinecarboxylic acid, CAS 50681-25-9, is a nitrogen-containing heteroaromatic carboxylic acid used primarily as a building block in organic and medicinal chemistry. Its molecular formula is C₅H₄N₂O₂ and its molecular weight is 124.10. Structurally, it consists of a pyridazine ring bearing a carboxylic acid group at the 4-position. This compact combination provides both a heteroaromatic recognition element and a versatile functional group for further bond formation.

Pyridazine is a six-membered aromatic ring containing two adjacent nitrogen atoms. It belongs to the diazine family, together with pyrimidine and pyrazine. Although all three contain two ring nitrogens, the positions of those nitrogens are different, which changes the electronic distribution, dipole moment, basicity, and substitution chemistry of the ring.

The adjacent nitrogens of pyridazine make the ring relatively electron deficient compared with benzene. This electronic character can influence both its chemical reactivity and the way pyridazine-containing molecules interact with proteins, metal centers, and other molecular environments. For medicinal chemists, the ring is attractive because it provides a compact, polar aromatic unit that can be incorporated without adding substantial molecular size.

The carboxylic acid at the 4-position provides the main synthetic connection point. Like other aromatic carboxylic acids, 4-pyridazinecarboxylic acid can be converted into esters, amides, activated acyl derivatives, and related compounds. This makes it particularly convenient for connecting the pyridazine ring to amines or other nucleophilic molecular fragments.

Amide formation is one of the most frequently used transformations in medicinal chemistry. A carboxylic acid is activated and then reacted with an amine, producing a new carbon-nitrogen bond. By keeping the pyridazine ring constant while changing the amine partner, chemists can rapidly prepare a family of related compounds.

Published patent literature provides a clear example. In one medicinal-chemistry program involving substituted pyrrolo[3,4-d]pyrimidines, 4-pyridazinecarboxylic acid was coupled with a nitrogen-containing bicyclic intermediate to form an amide whose carbonyl group directly links the pyridazine ring to the larger heterocyclic scaffold.

This transformation illustrates why small heteroaromatic acids are valuable building blocks. The acid itself does not need to contain the complexity of the final molecule. Its role is to deliver a defined heteroaromatic fragment together with a chemically convenient attachment point.

The pyridazine ring then becomes part of the final molecular architecture. Unlike a protecting group or temporary reagent, it is generally intended to remain after coupling. The carboxylic acid functionality is transformed, but the heteroaromatic ring survives as a permanent structural element.

Other patent literature shows a different type of use. 4-Pyridazinecarboxylic acid has served as a starting material in the preparation of substituted trifluoromethyl-containing pyridazine derivatives. In those sequences, the pyridazine carboxyl functionality participates in multistep transformations leading to more highly substituted heteroaromatic molecules.

These examples demonstrate two general synthetic roles. In one case, the carboxylic acid is directly converted into an amide and acts as a molecular connector. In another, it participates in a longer sequence in which both the carboxyl carbon and the heteroaromatic ring contribute to a more extensively modified product.

The chemistry of 4-pyridazinecarboxylic acid also illustrates the importance of positional isomers. Pyridazine carboxylic acids can place the carboxyl group at different ring positions, and these isomers are not interchangeable. Moving the acid from one carbon to another changes the geometry of the molecule, the direction in which a new amide or ester projects into space, and the electronic relationship between the carboxyl group and the two ring nitrogens.

This matters greatly in medicinal chemistry. A carboxamide attached at one ring position may orient a substituent toward a protein binding pocket, while the corresponding positional isomer may point the same group in a different direction. Small changes in substitution pattern can therefore produce large changes in biological activity.

The pyridazine ring itself has appeared frequently in drug discovery because its adjacent nitrogen atoms create a distinctive pattern of hydrogen-bond acceptance and polarity. The ring can also alter solubility and electronic properties compared with a phenyl group of similar size. These effects depend on the complete molecule and should not be treated as universal advantages, but they explain why pyridazine remains a useful heteroaromatic scaffold.

4-Pyridazinecarboxylic acid is therefore best understood as a compact molecular junction. One part of the molecule, the pyridazine ring, contributes a defined heteroaromatic shape and electronic character. The other part, the carboxylic acid, provides a highly versatile site for chemical connection.

This division of labor is one of the reasons small heteroaromatic carboxylic acids are so useful in pharmaceutical research. They allow chemists to separate molecular recognition from molecular assembly: preserve the ring that may influence biological interactions, while using the acid group to attach that ring to an increasingly complex framework.

The molecule is simple enough to fit in a few atoms, yet versatile enough to appear in very different synthetic programs. Its importance does not come from one famous final product, but from a general capability: it lets chemists place a pyridazine ring exactly where a synthetic design requires one, then connect that ring to the rest of the molecule through reliable carboxylic-acid chemistry.

References

1. PubChem. Pyridazine-4-carboxylic Acid. CAS 50681-25-9. Molecular formula C₅H₄N₂O₂; molecular weight 124.10.

2. Sigma-Aldrich. 4-Pyridazinecarboxylic acid, CAS 50681-25-9.

3. WO 2018/066718 A1. Therapeutic Compounds. Use of 4-pyridazinecarboxylic acid in the preparation of pyrrolo[3,4-d]pyrimidine derivatives.

4. WO 2009/040288 A1. 1,1,1-Trifluoro-2-hydroxy-3-phenylpropane derivatives. Use of 4-pyridazinecarboxylic acid in the preparation of substituted pyridazine derivatives.

5. Joule, J. A.; Mills, K. Heterocyclic Chemistry. Chemistry and properties of diazines and heteroaromatic carboxylic acids.