2-Chloronicotinic acid
[CAS# 2942-59-8]

Identification

• Classification: Chemical pesticide >> Herbicide >> Sulfonylurea herbicide
• Name: 2-Chloronicotinic acid
• Synonyms: 2-Chloro-3-pyridinecarboxylic acid
• Molecular Formula: C₆H₄ClNO₂
• Molecular Weight: 157.56
• CAS Registry Number: 2942-59-8
• EC Number: 220-937-0
• SMILES: C1=CC(=C(N=C1)Cl)C(=O)O

Properties

• Density: 1.5±0.1 g/cm³, Calc.^*
• Melting point: 176-178 °C (Expl.)
• Index of Refraction: 1.590, Calc.^*
• Boiling Point: 316.8±22.0 °C (760 mmHg), Calc.^*
• Flash Point: 145.4±22.3 °C, 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
Eye irritation	Eye Irrit.	2	H319
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2A	H319
Germ cell mutagenicity	Muta.	2	H341

Discovery and Applications

2-Chloronicotinic acid is a halogenated derivative of nicotinic acid (also known as niacin or vitamin B3), featuring a chlorine atom at the 2-position on the pyridine ring. The molecular formula of 2-chloronicotinic acid is C6H4ClNO2, and it is a white to light tan solid with a weakly acidic character. As a halogenated aromatic carboxylic acid, 2-chloronicotinic acid is primarily synthesized through chlorination of nicotinic acid under controlled conditions. This modification introduces a chlorine atom into the molecular structure, altering the compound's reactivity and potential applications.

The discovery of 2-chloronicotinic acid is rooted in the broader field of halogenated pyridine derivatives, which are studied for their biological and chemical properties. Halogenated nicotinic acid derivatives, like 2-chloronicotinic acid, are of particular interest because the introduction of a halogen atom to the pyridine ring can significantly influence the compound's electronic properties and reactivity, making it valuable in various chemical transformations.

One of the major applications of 2-chloronicotinic acid lies in the field of pharmaceuticals, where it serves as a precursor for the synthesis of bioactive molecules. It has been used in the development of compounds with antimicrobial, anti-inflammatory, and anticancer properties. The introduction of a chlorine atom at the 2-position makes the pyridine ring more reactive toward nucleophilic substitution, enabling further functionalization that can lead to new compounds with enhanced biological activities. For example, 2-chloronicotinic acid has been investigated in the synthesis of inhibitors for various enzymes, particularly those involved in the regulation of inflammation and immune responses.

In addition to its use in medicinal chemistry, 2-chloronicotinic acid also plays a role in material science. It is utilized as a building block in the synthesis of metal-organic frameworks (MOFs), which are porous materials with applications in gas storage, catalysis, and separation processes. The presence of the chlorination on the pyridine ring can modulate the coordination chemistry of the molecule, making it suitable for incorporation into MOF structures. The versatility of 2-chloronicotinic acid as a ligand in these materials is significant because it allows the fine-tuning of their properties for specific applications.

Furthermore, 2-chloronicotinic acid has been employed in the synthesis of agrochemicals, including herbicides and insecticides. The chlorine substitution enhances the compound's lipophilicity and stability, making it more effective in interacting with biological targets. It has also been explored as an intermediate in the synthesis of nicotinic acid derivatives that can be used in crop protection. These agrochemical applications rely on the compound's ability to act as a potent bioactive agent while being relatively stable under environmental conditions.

In synthetic chemistry, 2-chloronicotinic acid serves as a versatile intermediate in the preparation of other important chemicals. It is involved in reactions like Suzuki and Heck coupling, where its halogen atom participates in cross-coupling processes to form carbon-carbon bonds. These reactions are crucial in the construction of complex molecules, such as pharmaceuticals and fine chemicals, and in the production of specialty polymers and materials.

In conclusion, 2-chloronicotinic acid is a valuable chemical intermediate with diverse applications in medicinal chemistry, materials science, and agrochemical synthesis. Its halogenated structure enhances its reactivity, making it useful in a variety of chemical reactions that lead to the development of bioactive compounds and advanced materials. As research into its applications continues, it is likely that 2-chloronicotinic acid will play an increasingly important role in the synthesis of new therapeutics, functional materials, and agrochemicals.

References

2013. Synthesis, anti-inflammatory and analgesic activities of arylidene-2-(3-chloroanilino)nicotinic acid hydrazides. Medicinal Chemistry Research, 22(6).
DOI: 10.1007/s00044-013-0860-5

2019. Synthesis of azachromones and azachromanones. Chemistry of Heterocyclic Compounds, 55(9).
DOI: 10.1007/s10593-019-02570-x

2020. Hydrogen bonding supramolecular networks of copper(II) 2-choronicotinate complexes with picolinamide, nicotinamide, N-methyl-nicotinamide, 2-pyridylmethanol and 4-pyridylmethanol: Hirshfeld surface analysis and spectral properties. Chemical Papers, 74(12).
DOI: 10.1007/s11696-020-01224-z