2-[(2-Methoxyphenyl)[(4-methylphenyl)sulfonyl]amino]-N-(4-methoxy-3-pyridinyl)acetamide
[CAS 1890208-58-8]

Identification

• Classification: Chemical reagent >> Organic reagent >> Amide
• Name: 2-[(2-Methoxyphenyl)[(4-methylphenyl)sulfonyl]amino]-N-(4-methoxy-3-pyridinyl)acetamide
• Synonyms: 2-((N-(2-Methoxyphenyl)-4-methylphenyl)sulfonamido)-N-(4-methoxypyridin-3-yl)acetamide
• Molecular Formula: C₂₂H₂₃N₃O₅S
• Molecular Weight: 441.50
• CAS Registry Number: 1890208-58-8
• SMILES: CC1=CC=C(C=C1)S(=O)(=O)N(CC(=O)NC2=C(C=CN=C2)OC)C3=CC=CC=C3OC

Properties

• Solubility: Practically insoluble (0.066 g/L) (25 °C), Calc.^*
• Density: 1.329±0.06 g/cm³ (20 °C 760 Torr), Calc.^*
• Index of refraction: 1.623 (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-P270-P271-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P330-P332+P313-P337+P313-P362-P403+P233-P405-P501

Discovery and Applications

2-[(2-Methoxyphenyl)[(4-methylphenyl)sulfonyl]amino]-N-(4-methoxy-3-pyridinyl)acetamide is a synthetic aromatic sulfonamide–acetamide compound containing multiple heteroaromatic and electron-withdrawing functional groups. Structurally, it is built around an acetamide core that is substituted on one side by a sulfonylated diarylamine fragment and on the other by a substituted methoxypyridine ring.

The molecule contains three major structural domains. The first is a sulfonamide-derived diaryl unit in which a nitrogen atom is bonded to both a 2-methoxyphenyl group and a 4-methylphenylsulfonyl group. Sulfonamide functional groups are characterized by a sulfur atom double-bonded to two oxygen atoms and single-bonded to nitrogen and carbon, creating a strongly polarized S=O environment. This group is highly electron-withdrawing and significantly influences the acidity of the adjacent nitrogen and the overall electronic distribution of the molecule.

The second domain is the acetamide linker. The acetamide group (–NH–CO–CH₂–) contains a carbonyl that is strongly polarized and capable of acting as a hydrogen-bond acceptor, while the amide nitrogen can participate as a hydrogen-bond donor depending on substitution. The acetamide linkage serves as a flexible connector between the sulfonamide and heteroaromatic fragments, allowing spatial separation of the two aromatic systems.

The third domain is the N-(4-methoxy-3-pyridinyl) substituent. This portion contains a pyridine ring, which is a six-membered nitrogen-containing heteroaromatic system. The ring nitrogen decreases electron density in the aromatic system and can act as a weak base and hydrogen-bond acceptor. The presence of a methoxy group further modifies electron distribution by donating electron density through resonance, increasing aromatic electron richness relative to unsubstituted pyridine. The substitution pattern creates an asymmetric electronic environment within the heteroaromatic ring.

Overall, the molecule contains both electron-rich and electron-deficient aromatic regions. The methoxy-substituted phenyl and pyridine rings tend to donate electron density through resonance effects, while the sulfonyl group is strongly electron-withdrawing. This combination produces a highly polarized molecular framework with multiple sites for intermolecular interactions.

From a conformational perspective, the sulfonamide bond exhibits partial double-bond character due to resonance between nitrogen and the sulfonyl group, restricting rotation and contributing to a relatively defined geometry. The acetamide bond also has partial double-bond character, further limiting conformational freedom. As a result, the molecule is expected to adopt a constrained set of low-energy conformations rather than being highly flexible.

The compound contains several heteroatoms, including oxygen, nitrogen, and sulfur, which contribute to hydrogen bonding and dipole interactions. These features generally increase polarity and influence solubility behavior. However, the presence of multiple aromatic rings and methyl/methoxy substituents introduces hydrophobic character, resulting in an amphiphilic balance.

In terms of chemical stability, amide and sulfonamide linkages are generally stable under neutral conditions but can undergo hydrolysis under strongly acidic or basic environments. The aromatic ether (methoxy) groups are relatively stable under mild conditions but may be cleaved under strong nucleophilic or acidic conditions.

Without verified literature specific to this compound, no statements can be made regarding biological activity or application. Based solely on structural analysis, it can be reliably described as a highly functionalized sulfonamide–acetamide system containing multiple substituted aromatic and heteroaromatic rings, with strong electronic polarization and restricted conformational flexibility due to resonance-stabilized amide and sulfonamide linkages.

References

2016. Discovery, Optimization, and Biological Evaluation of Sulfonamidoacetamides as an Inducer of Axon Regeneration. Journal of Medicinal Chemistry.
DOI: 10.1021/acs.jmedchem.6b00015