2-Methoxy-5-(methylsulfonyl)benzoic acid
[CAS# 50390-76-6]

Identification

• Classification: Organic raw materials >> Carboxylic compounds and derivatives
• Name: 2-Methoxy-5-(methylsulfonyl)benzoic acid
• Molecular Formula: C₉H₁₀O₅S
• Molecular Weight: 230.23
• CAS Registry Number: 50390-76-6
• EC Number: 256-573-4
• SMILES: COC1=C(C=C(C=C1)S(=O)(=O)C)C(=O)O

Properties

• Density: 1.4±0.1 g/cm³ Calc.^*
• Boiling point: 467.9±45.0 ºC 760 mmHg (Calc.)^*
• Flash point: 236.8±28.7 ºC (Calc.)^*
• Index of refraction: 1.543 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319-H335
• Precautionary 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.	2A	H319
Acute toxicity	Acute Tox.	4	H302
Eye irritation	Eye Irrit.	2	H319

Discovory and Applicatios

2-Methoxy-5-(methylsulfonyl)benzoic acid is an aromatic carboxylic acid derivative characterized by a benzene ring substituted with three distinct functional groups: a methoxy group (-OCH₃) at the 2-position, a methylsulfonyl group (-SO₂CH₃) at the 5-position, and a carboxylic acid (-COOH) group. Its molecular formula is C₉H₁₀O₅S, indicating the presence of carbon, hydrogen, oxygen, and sulfur atoms.

The methoxy group at the ortho position relative to the carboxyl group is an electron-donating substituent via resonance, influencing the electronic distribution of the aromatic ring. This substituent can affect the acidity of the carboxylic acid and reactivity of the molecule toward electrophilic and nucleophilic aromatic substitution reactions.

The methylsulfonyl group at the meta position is a strong electron-withdrawing moiety due to the presence of the sulfone functional group, which contains a sulfur atom doubly bonded to two oxygen atoms and bonded to a methyl group. This group enhances the molecule’s polarity and can significantly affect its chemical behavior, including increased hydrophilicity and potential for hydrogen bonding interactions.

The carboxylic acid group imparts acidic character to the molecule, allowing it to participate in acid-base reactions, form salts and esters, and engage in hydrogen bonding. This group also serves as a synthetic handle for further functionalization, enabling the formation of amides, anhydrides, or coordination complexes.

Synthetically, 2-methoxy-5-(methylsulfonyl)benzoic acid can be prepared through sulfonylation of appropriate methoxybenzoic acid precursors, typically involving oxidation of methylthio substituents to methylsulfonyl groups or direct introduction of the sulfonyl moiety using sulfonylating reagents. The methoxy group is commonly introduced via methylation of hydroxyl-substituted precursors.

The compound’s physicochemical properties include moderate solubility in polar organic solvents such as methanol, ethanol, and dimethyl sulfoxide, with limited solubility in water due to the hydrophobic aromatic ring. It usually appears as a crystalline solid with a defined melting point.

In medicinal chemistry and material science, derivatives of methoxybenzoic acid and sulfonyl-substituted benzoic acids are studied for their biological activity and utility as intermediates in drug synthesis, polymer production, and as ligands in coordination chemistry. The combination of electron-donating and electron-withdrawing groups in 2-methoxy-5-(methylsulfonyl)benzoic acid offers a versatile scaffold for chemical modification.

In summary, 2-methoxy-5-(methylsulfonyl)benzoic acid is a multifunctional aromatic carboxylic acid featuring both electron-donating and electron-withdrawing substituents. Its structural diversity and reactive sites make it a valuable compound in synthetic organic chemistry and potential applications in pharmaceuticals and materials science.

References

2007. Stability-Indicating Methods for Determination of Tiapride in Pure Form, Pharmaceutical Preparation, and Human Plasma. Journal of AOAC INTERNATIONAL, 90(6).
DOI: 10.1093/jaoac/90.6.1554

2009. A Simple and Rapid CZE Determination of Tiapride Hydrochloride and Related Impurities in Pharmaceutical Formulations. Chromatographia, 70(3-4).
DOI: 10.1365/s10337-009-1140-x