2-Methylquinolin-4-amine
[CAS 6628-04-2]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Quinoline compound
• Name: 2-Methylquinolin-4-amine
• Synonyms: 2-Methylquinolin-4-ylamine; 4-Amino-2-methylquinoline; 4-Aminoquinaldine
• Molecular Formula: C₁₀H₁₀N₂
• Molecular Weight: 158.2
• CAS Registry Number: 6628-04-2
• EC Number: 229-604-4
• SMILES: CC1=NC2=CC=CC=C2C(=C1)N

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*
• Melting point: 162 - 166 °C (Expl.)
• Boiling point: 327.4±27.0 °C 760 mmHg (Calc.)^*, 333 °C (Expl.)
• Flash point: 178.0±10.9 °C (Calc.)^*
• Index of refraction: 1.682 (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
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2	H319
Serious eye damage	Eye Dam.	1	H318
Acute toxicity	Acute Tox.	4	H302
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411
Eye irritation	Eye Irrit.	2A	H319
Acute toxicity	Acute Tox.	3	H301
Skin sensitization	Skin Sens.	1B	H317

Discovery and Applications

2-Methylquinolin-4-amine is a substituted quinoline derivative in which a methyl group is attached at the 2-position of the quinoline ring system and an amino group is present at the 4-position. Quinoline is a fused bicyclic heteroaromatic compound composed of a benzene ring fused to a pyridine ring, and it is a well-established structural motif in organic and medicinal chemistry.

The quinoline framework is aromatic and contains a nitrogen atom in the pyridine-like portion of the fused system. This nitrogen atom influences the electronic distribution of the molecule, making the heterocycle electron-deficient relative to benzene. As a result, quinoline derivatives often exhibit distinct reactivity patterns in electrophilic and nucleophilic substitution reactions compared with purely carbocyclic aromatics.

In 2-methylquinolin-4-amine, the methyl substituent at position 2 is electron-donating through inductive effects and increases electron density locally on the ring. This substitution can slightly modulate the reactivity of the quinoline system by reducing electron deficiency in adjacent positions. The methyl group also introduces steric effects that can influence molecular conformation and intermolecular interactions in the solid state.

The amino group at the 4-position is a primary aromatic amine functionality, which is strongly electron-donating through resonance. This group significantly increases electron density on the quinoline ring and can alter its chemical reactivity. The lone pair on the nitrogen atom is partially delocalized into the aromatic system, enhancing conjugation and affecting the electronic distribution across the fused ring structure. This also makes the amino group a key site for protonation and derivatization reactions.

Quinoline amines are often basic compounds due to the presence of both a ring nitrogen and an exocyclic amino group. The basicity of the molecule depends on the relative availability of the lone pairs on these nitrogen atoms, with protonation typically occurring at the more basic site depending on environmental conditions. In aqueous acidic media, protonated forms can exist as quinolinium salts, which are more water soluble.

From a structural perspective, the fused aromatic system is planar or near-planar, allowing extensive π-electron delocalization across the ring system. This conjugation contributes to the stability of the molecule and influences its optical and electronic properties. Substitution at different positions of the quinoline core can significantly affect reactivity and binding behavior in biological systems.

Compounds containing amino-substituted quinoline scaffolds are widely studied in medicinal chemistry because they can interact with biological targets such as enzymes, receptors, and nucleic acids. The combination of aromaticity, hydrogen bonding capability, and adjustable electronic properties makes quinoline derivatives useful as pharmacophores in drug design.

The presence of both methyl and amino substituents also affects the compound’s physicochemical properties. The methyl group contributes hydrophobic character, while the amino group increases polarity and hydrogen bonding capacity. As a result, 2-methylquinolin-4-amine exhibits mixed hydrophilic and lipophilic characteristics, which can influence solubility and membrane permeability.

In terms of chemical reactivity, the amino group can undergo acylation, alkylation, and diazotization reactions, allowing further functionalization of the molecule. The quinoline ring itself can participate in substitution reactions under appropriate conditions, particularly when activated by electron-donating substituents such as the amino group.

Overall, 2-methylquinolin-4-amine is a functionalized quinoline derivative featuring a fused aromatic heterocycle with both electron-donating methyl and amino substituents. Its significance lies in its tunable electronic structure, reactivity of the amino group, and relevance as a building block in heterocyclic and medicinal chemistry.

References

2026. High-throughput reaction screening using acoustic ejection mass spectrometry. Nature Protocols.
DOI: 10.1038/s41596-025-01320-y

2026. Synthesis, Properties, and Applications of Aminoquinoline-Derived Schiff Bases and Their Metal Complexes. Russian Journal of Bioorganic Chemistry.
DOI: 10.1134/s1068162025601880