3,5-Dimethyl-4-methoxybenzoic acid
[CAS# 21553-46-8]

Identification

• Classification: Organic raw materials >> Carboxylic compounds and derivatives
• Name: 3,5-Dimethyl-4-methoxybenzoic acid
• Synonyms: 3,5-Dimethyl-p-anisic acid
• Molecular Formula: C₁₀H₁₂O₃
• Molecular Weight: 180.20
• CAS Registry Number: 21553-46-8
• EC Number: 244-441-9
• SMILES: CC1=CC(=CC(=C1OC)C)C(=O)O

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*
• Melting point: 191 - 195 °C (Expl.)
• Boiling point: 293.5±35.0 °C 760 mmHg (Calc.)^*
• Flash point: 113.8±19.4 °C (Calc.)^*
• Index of refraction: 1.537 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS06;GHS07 Danger
• Risk Statements: H301-H319
• Safety Statements: P264-P264+P265-P270-P280-P301+P316-P305+P351+P338-P321-P330-P337+P317-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Eye irritation	Eye Irrit.	2	H319
Acute toxicity	Acute Tox.	3	H301
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2A	H319

• Transport Information: UN 2811

Discovery and Applications

3,5-Dimethyl-4-methoxybenzoic acid is an aromatic carboxylic acid derivative in which a benzene ring is substituted with methyl groups at the 3 and 5 positions, a methoxy group at position 4, and a carboxyl group at position 1. Its molecular formula is C₁₀H₁₂O₃, and it has a molecular weight of approximately 180.20 g/mol. The combination of electron-donating methyl and methoxy groups with the electron-withdrawing carboxyl group creates a distinct electronic environment that influences both reactivity and physical properties.

The compound is generally synthesized by selective methylation and methoxylation of the corresponding benzoic acid or by controlled oxidation of substituted aromatic precursors. Methods include electrophilic aromatic substitution to introduce methyl groups at the 3 and 5 positions, followed by etherification to install the methoxy group at position 4. Protecting groups may be employed to prevent reaction at the carboxyl group during methylation or methoxylation, ensuring regioselective functionalization.

Chemically, 3,5-dimethyl-4-methoxybenzoic acid exhibits the typical reactivity of substituted aromatic carboxylic acids. The carboxyl group can undergo esterification, amidation, or activation for further coupling reactions, while the methoxy and methyl groups influence the rate and regioselectivity of electrophilic aromatic substitution. The methoxy group, in particular, is an electron-donating substituent that activates the ring toward electrophilic attack at positions ortho and para to itself, though the existing methyl groups partially block these positions, directing reactivity in predictable ways.

The presence of the methoxy and methyl substituents also affects solubility and acidity. The carboxyl group remains acidic, capable of forming salts with bases, while the hydrophobic methyl and methoxy groups enhance solubility in organic solvents such as ethanol, acetone, and dichloromethane. This balance of hydrophilic and lipophilic properties makes the compound suitable for use in both polar and moderately nonpolar reaction media.

In synthetic applications, 3,5-dimethyl-4-methoxybenzoic acid is often used as a building block for the preparation of functionalized aromatic derivatives. Its defined substitution pattern allows selective derivatization at the carboxyl group while maintaining steric and electronic control over the aromatic ring. This feature is valuable in the design of pharmaceuticals, agrochemicals, and organic materials where precise substitution is necessary to achieve desired biological or physical properties.

The compound is generally a solid at room temperature with moderate thermal stability. It should be protected from strong oxidizing agents that could alter the methoxy or methyl substituents, and from strong bases that could deprotonate the carboxyl group or induce side reactions. Handling precautions include avoiding inhalation of dust and using gloves to prevent skin contact, as with most aromatic carboxylic acids.

Overall, 3,5-dimethyl-4-methoxybenzoic acid combines a reactive carboxyl group with a sterically defined, electron-rich aromatic system, making it a versatile intermediate for organic synthesis. Its substitution pattern allows both selective functionalization and predictable chemical behavior, supporting applications in medicinal chemistry, material science, and synthetic methodology.

References

2021. Formation of C—O Bonds. Science of Synthesis.
URL: SD-137-00167

2011. Propylphosphonic Anhydride (T3P®)-Mediated One-Pot Rearrangement of Carboxylic Acids to Carbamates. Synthesis.
DOI: 10.1055/s-0030-1259964