4-Amino-2-chloropyridine
[CAS# 14432-12-3]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyridine compound >> Aminopyridine
• Name: 4-Amino-2-chloropyridine
• Synonyms: 2-Chloro-4-pyridinamine
• Molecular Formula: C₅H₅ClN₂
• Molecular Weight: 128.56
• CAS Registry Number: 14432-12-3
• EC Number: 238-403-0
• SMILES: C1=CN=C(C=C1N)Cl

Properties

• Density: 1.3±0.1 g/cm³, Calc.^*
• Melting point: 90-94 °C (Expl.)
• Index of Refraction: 1.607, Calc.^*
• Boiling Point: 299.9±20.0 °C (760 mmHg), Calc.^*, 350.6 °C (Expl.)
• Flash Point: 135.2±21.8 °C, Calc.^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H312-H315-H319-H332-H335
• Safety Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P317-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
Specific target organ toxicity - single exposure	STOT SE	3	H335
Acute toxicity	Acute Tox.	4	H312
Acute toxicity	Acute Tox.	4	H302
Acute toxicity	Acute Tox.	4	H332
Acute toxicity	Acute Tox.	3	H301
Acute toxicity	Acute Tox.	3	H331
Eye irritation	Eye Irrit.	2A	H319
Acute toxicity	Acute Tox.	3	H311

Discovery and Applications

4-Amino-2-chloropyridine is an aromatic heterocyclic compound with the molecular formula C₅H₅ClN₂. It consists of a pyridine ring substituted at the 2-position with a chlorine atom and at the 4-position with an amino group. This compound belongs to the class of chloropyridine derivatives, which are frequently studied due to their chemical reactivity and utility in pharmaceutical and agrochemical synthesis.

The synthesis of 4-amino-2-chloropyridine has been documented through several reliable and reproducible methods. One of the most established routes involves the nucleophilic substitution of 2,4-dichloropyridine, where the chlorine atom at the 4-position is replaced by an amino group using ammonia or an amine source under appropriate conditions. This selective substitution exploits the differential reactivity of halogenated positions on the pyridine ring. The reaction conditions are typically mild, and the product is obtained with good yields and purity after purification by recrystallization or chromatographic methods.

4-Amino-2-chloropyridine is a valuable intermediate in the synthesis of more complex nitrogen-containing compounds. The presence of both an electron-donating amino group and an electron-withdrawing chlorine atom on the pyridine ring enhances its reactivity in various transformations, including cross-coupling reactions and heterocycle formation. The amino group serves as a nucleophilic center, enabling acylation, sulfonation, and diazotization reactions. Meanwhile, the chlorine atom at the 2-position can undergo substitution via palladium-catalyzed cross-coupling methods such as Suzuki, Heck, or Buchwald-Hartwig reactions, allowing for the formation of C–C or C–N bonds.

In medicinal chemistry, 4-amino-2-chloropyridine is widely used as a building block in the development of bioactive compounds. It is employed in the synthesis of various pharmaceutical candidates, particularly those targeting kinase enzymes, bacterial infections, and inflammatory pathways. The compound’s pyridine nucleus is known to exhibit favorable pharmacokinetic properties, and its substitution pattern allows for the generation of derivatives with high binding specificity and metabolic stability.

Several derivatives of 4-amino-2-chloropyridine have been reported in the literature with demonstrated biological activities. For example, it has been used as a precursor for the preparation of inhibitors targeting protein tyrosine kinases and cyclin-dependent kinases. It also appears in synthetic routes leading to pyridine-based ureas, amides, and sulfonamides, which are known classes of compounds with antibacterial, antiviral, and anticancer applications. While the parent compound itself is not typically used as a drug, its role in facilitating access to bioactive molecules is well recognized.

In the field of agrochemical research, 4-amino-2-chloropyridine has found use in the synthesis of herbicidal and fungicidal agents. Pyridine derivatives are frequently incorporated into agrochemical structures due to their ability to interfere with plant or microbial biochemical processes. The structural framework of 4-amino-2-chloropyridine allows for chemical diversification, which supports the discovery of compounds with selective activity against agricultural pests or pathogens.

Analytical characterization of 4-amino-2-chloropyridine is routinely conducted using techniques such as nuclear magnetic resonance spectroscopy, mass spectrometry, and infrared spectroscopy. In NMR spectra, signals corresponding to the pyridine ring protons, as well as the amino group, provide clear evidence of the compound’s structure. The infrared spectrum typically shows characteristic bands for N–H stretching and C–Cl vibrations. The compound is generally isolated as a crystalline solid, with good stability under ambient storage conditions, and is soluble in polar organic solvents such as ethanol, methanol, and dimethylformamide.

The compound should be handled with care, as is standard for halogenated and aminated aromatic substances. Appropriate personal protective equipment and ventilation are required during handling and synthesis.

4-Amino-2-chloropyridine continues to serve as a versatile and well-studied intermediate in organic and medicinal chemistry, with a clearly documented history of applications across both industrial and academic research settings.

References

2024. Physical and Chemical Characterisations, Optical Properties and Dielectric Studies of a New Organic-Inorganic Material: bis(4-amino-2-chloropyridinium) Tetrachloromercurate (II) Monohydrate. Chemistry Africa, 7(3).
DOI: 10.1007/s42250-023-00813-1

2023. Exploiting Ion-Dipole and Ion-Exchange Interactions for the Removal of Aminopyridines from Aqueous Environments Using Polymer Inclusion Membranes. Chemistry Africa, 6(5).
DOI: 10.1007/s42250-023-00734-z

2018. Preparation, molecular structure, thermal properties, electrical conductivity analysis and dielectric relaxation of a new hybrid compound (NH2C5H3ClNH)2ZnBr4·H2O. Chemical Papers, 72(12).
DOI: 10.1007/s11696-018-0521-8