3-Methoxy-5-methylphenylamine
[CAS# 66584-31-4]

Identification

• Classification: Organic raw materials >> Aryl compounds >> Anilines
• Name: 3-Methoxy-5-methylphenylamine
• Molecular Formula: C₈H₁₁NO
• Molecular Weight: 137.18
• CAS Registry Number: 66584-31-4
• SMILES: CC1=CC(=CC(=C1)OC)N

Properties

• Density: 1.0±0.1 g/cm³ Calc.^*
• Boiling point: 257.7±20.0 °C 760 mmHg (Calc.)^*
• Flash point: 120.2±15.0 °C (Calc.)^*
• Index of refraction: 1.549 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety Statements: P261-P305+P351+P338

Discovery and Applications

3‑Methoxy‑5‑methylphenylamine (also known as 3‑methoxy‑5‑methylaniline, CAS 66584‑31‑4) is an aromatic amine derivative with molecular formula C₈H₁₁NO and molecular weight ~137.18 g/mol. It appears as a white‑to‑yellow crystalline solid under typical conditions.

The compound is primarily used as a synthetic building block (intermediate) in organic chemistry. Its structure, featuring both a methoxy group (–OCH₃) at the 3‑position and a methyl group (–CH₃) at the 5‑position on the aniline ring, provides useful electronic and steric properties. The amino (–NH₂) functionality enables further derivatization, while the methoxy and methyl substituents influence reactivity and regioselectivity.

One of the main applications of 3‑methoxy‑5‑methylaniline is in the synthesis of sulfonamide derivatives. Such sulfonamides often exhibit antimicrobial activity. In particular, N‑substituted sulfonamides derived from 3‑methoxy-5-methylaniline have been reported and studied. These derivatives can be tailored for biological screening, for example, in anti-microbial or enzyme-inhibition assays.

The amine can also be employed in the construction of more complex aromatic structures. Through typical aromatic-amine chemistry, it serves as a precursor to N‑alkylated or N‑acylated aniline derivatives. Because of the activating effect of the methoxy group and the moderately electron-donating methyl group, electrophilic aromatic substitution (or other functionalization) at certain ring positions is facilitated, allowing its incorporation into heterocycles or advanced pharmaceutical intermediates.

On the synthetic side, routes to prepare 3‑methoxy-5-methylaniline typically involve starting from appropriately substituted nitro or chloro arenes, followed by methoxylation and reduction. After the target aniline is obtained, it can be purified and used as an intermediate.

From a safety perspective, the compound should be handled with standard precautions for aromatic amines. According to its safety data, it may cause skin and eye irritation, and inhalation should be avoided — protective gloves, goggles, and adequate ventilation are recommended.

Because of these attributes — a reactive amino group, tunable substitution, and relatively straightforward synthetic accessibility — 3‑methoxy-5-methylphenylamine is a valuable intermediate in medicinal chemistry, agrochemical development, and other applications that require functionalized aromatic amine scaffolds.

References

Rasool S, et al. (2013) Synthesis, spectral analysis and biological screening of various sulfonamides derived from substituted anilines. Journal of Molecular Structure 1044, 239–245. DOI: 10.1016/j.molstruc.2013.06.034

Nunes IKdC, de Souza ET, Cardozo SVS, Carvalho VdF, Romeiro NC, Silva PMRe, et al. (2016) Synthesis, Pharmacological Profile and Docking Studies of New Sulfonamides Designed as Phosphodiesterase‑4 Inhibitors. PLoS ONE 11(10): e0162895. DOI: 10.1371/journal.pone.0162895

Ali SA, Jabbir AH, Mohsie RA (2016) Synthesis of Some Sulfa Drug Derivatives as Antibacterial Agents. International Journal of Current Microbiology and Applied Sciences 5(5): 75–83. DOI: 10.20546/ijcmas.2016.505.008