N-methylpyridin-2-amine
[CAS# 4597-87-9]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyridine compound >> Aminopyridine
• Name: N-methylpyridin-2-amine
• Synonyms: N-methylpyridin-2-amine
• Molecular Formula: C₆H₈N₂
• Molecular Weight: 108.14
• CAS Registry Number: 4597-87-9
• EC Number: 224-997-9
• SMILES: CNC1=CC=CC=N1

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*, 1.052 g/mL (Expl.)
• Melting point: 15 °C (Expl.)
• Boiling point: 201.3±13.0 °C 760 mmHg (Calc.)^*, 200 - 201 °C (Expl.)
• Flash point: 87.8 °C (Calc.)^*, 88 °C (Expl.)
• Index of refraction: 1.579 (Calc.)^*, 1.578 (Expl.)

^* 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
Acute toxicity	Acute Tox.	4	H332
Specific target organ toxicity - single exposure	STOT SE	3	H335
Acute toxicity	Acute Tox.	4	H312
Acute toxicity	Acute Tox.	4	H302
Eye irritation	Eye Irrit.	2A	H319

Discovery and Applications

2-(Methylamino)pyridine is a heteroaromatic amine with the molecular formula C6H8N2. It consists of a pyridine ring substituted at the 2-position by a methylamino group, combining the basicity of both a ring nitrogen and a secondary amine. The compound typically appears as a colorless to pale yellow liquid or low-melting solid with a characteristic amine-like odor. It is soluble in water and most common organic solvents, reflecting its polar nature and ability to participate in hydrogen bonding.

The development and use of 2-(methylamino)pyridine are closely connected to the broader study of aminopyridines, which emerged as important building blocks in heterocyclic chemistry during the twentieth century. Pyridine derivatives attracted early interest because of their prevalence in natural products, pharmaceuticals, and coordination chemistry. Substituted aminopyridines, including 2-(methylamino)pyridine, were investigated for their distinctive electronic properties arising from the interaction between the pyridine nitrogen and the amino substituent. This interaction affects basicity, reactivity, and coordination behavior, making such compounds valuable in both academic research and industrial synthesis.

Synthesis of 2-(methylamino)pyridine is commonly achieved through nucleophilic substitution or amination reactions involving halogenated pyridines. A typical route involves the reaction of 2-chloropyridine or 2-fluoropyridine with methylamine under controlled conditions, often using elevated temperature and pressure to facilitate substitution at the 2-position. Alternative methods include reductive amination of 2-aminopyridine derivatives or catalytic coupling reactions that introduce the methylamino group selectively. The product is usually purified by distillation or crystallization to remove residual starting materials and by-products.

Chemically, 2-(methylamino)pyridine exhibits dual basicity due to the presence of both the ring nitrogen and the exocyclic amine. This makes it capable of forming salts with acids and coordinating to metal centers as a bidentate or monodentate ligand, depending on conditions. The electron-donating methylamino group influences the electron density of the pyridine ring, enhancing nucleophilicity at certain positions and affecting reactivity in electrophilic and substitution reactions. The compound can undergo typical amine reactions such as acylation, alkylation, and condensation, while the pyridine ring participates in metal-catalyzed coupling and heterocycle-forming reactions.

In practical applications, 2-(methylamino)pyridine is primarily used as an intermediate in the synthesis of pharmaceuticals, agrochemicals, and fine chemicals. It serves as a precursor for more complex heterocyclic systems, including fused-ring compounds and functionalized pyridines with biological activity. In medicinal chemistry, substituted aminopyridines are frequently incorporated into drug candidates to modulate binding affinity, solubility, and metabolic stability. The compound is also employed in coordination chemistry as a ligand or ligand precursor, contributing to the preparation of metal complexes used in catalysis and materials research.

Physically, 2-(methylamino)pyridine is stable under normal storage conditions but should be protected from moisture and strong oxidizing agents. As with many low-molecular-weight amines, it can be irritating to the skin, eyes, and respiratory system, and appropriate protective measures such as gloves and adequate ventilation are recommended during handling. It is typically stored in tightly sealed containers in a cool, dry environment.

Overall, 2-(methylamino)pyridine is a versatile heteroaromatic amine that plays an important role in synthetic chemistry. Its combination of a reactive amino substituent and a pyridine ring provides a balance of nucleophilicity, basicity, and structural rigidity, making it a valuable intermediate for the construction of pharmaceuticals, functional heterocycles, and coordination compounds used across chemical research and industry.

References

2024. Modelling and Optimization of Chlorpheniramine Treatment Using Anodic Oxidation Process on Boron Doped Diamond Electrode. Chemistry Africa.
DOI: 10.1007/s42250-024-01020-2

2022. Iridium-Catalyzed Asymmetric Alkylation of Cyclic Alkenes Using N-Methyl-2-Aminopyridines. Synfacts.
DOI: 10.1055/s-0042-1753068