Nefiracetam
[CAS 77191-36-7]

Identification

• Classification: API >> Nervous system medication >> Brain metabolism regulating drug
• Name: Nefiracetam
• Synonyms: N-(2,6-Dimethylphenyl)-2-oxo-1-pyrrolidineacetamide
• Molecular Formula: C₁₄H₁₈N₂O₂
• Molecular Weight: 246.31
• CAS Registry Number: 77191-36-7
• EC Number: 636-080-4
• SMILES: CC1=C(C(=CC=C1)C)NC(=O)CN2CCCC2=O

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*
• Melting point: 151-155 °C (Expl.)
• Boiling point: 458.5±33.0 °C 760 mmHg (Calc.)^*
• Flash point: 231.1±25.4 °C (Calc.)^*
• Solubility: DMSO 50 mg/mL, Water 5 mg/mL (Expl.)
• Index of refraction: 1.594 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H319
• Safety Statements: P264-P264+P265-P270-P280-P301+P317-P305+P351+P338-P330-P337+P317-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Eye irritation	Eye Irrit.	2	H319
Reproductive toxicity	Repr.	2	H361

Discovery and Applications

Nefiracetam is a synthetic compound belonging to the racetam class of nootropic agents, structurally derived from the 2-pyrrolidone (lactam) core shared by all racetams. It is characterized by a cyclic amide structure with a lipophilic aromatic substituent, which distinguishes it from earlier, more polar racetam analogues.

The central structural feature of nefiracetam is the 2-oxo-pyrrolidine ring, a five-membered lactam. This ring system is stabilized by resonance between the nitrogen lone pair and the carbonyl group, giving it partial double-bond character and reducing its reactivity under normal conditions. The lactam carbonyl functions as a hydrogen-bond acceptor, which contributes to intermolecular interactions and polarity.

Attached to the nitrogen of the lactam is an acetamide linker that connects to a para-substituted aromatic ether group. Specifically, the molecule contains a 2,6-dimethylphenyl moiety linked through an ether oxygen to a substituted acetamide chain. This aromatic portion contributes significant hydrophobic character and π-electron density, influencing both molecular shape and physicochemical properties.

The presence of the aromatic ring increases lipophilicity compared with simpler racetams such as piracetam or oxiracetam. The methyl substituents on the phenyl ring further enhance hydrophobicity and steric bulk, affecting how the molecule fits into binding environments and how it partitions between aqueous and lipid phases.

The ether linkage (–O–) between the aromatic ring and the rest of the molecule introduces an oxygen atom capable of acting as a hydrogen-bond acceptor. This contributes moderate polarity despite the overall hydrophobic nature of the aromatic system. The balance between polar lactam/amide groups and hydrophobic aromatic groups gives nefiracetam amphiphilic characteristics.

The acetamide portion of the molecule contains a carbonyl group and an amide nitrogen. Like other amides, this functional group is resonance-stabilized, reducing its basicity and reactivity. The carbonyl oxygen can participate in hydrogen bonding, which contributes to the compound’s interaction profile in aqueous environments.

From a conformational standpoint, nefiracetam has both rigid and flexible elements. The lactam ring is rigid, while the acetamide linker and ether-containing side chain allow rotational freedom. The aromatic ring is planar, and its orientation relative to the rest of the molecule can influence intermolecular interactions.

Nefiracetam is overall a neutral compound under physiological conditions, lacking strongly ionizable functional groups. This neutrality, combined with its mixed polar and nonpolar regions, influences its solubility and membrane permeability behavior.

Chemically, the amide and lactam bonds are generally stable under neutral conditions, though they can undergo hydrolysis under strong acidic or basic environments. The ether linkage is relatively stable, and the aromatic ring is chemically robust under normal conditions.

Nefiracetam is part of the broader racetam family, which shares a common 2-pyrrolidone nucleus but differs in side-chain substitutions that modify lipophilicity, polarity, and conformational properties. Compared with earlier racetams, nefiracetam is more lipophilic and structurally complex due to its aromatic ether substituent.

Overall, nefiracetam is a synthetic pyrrolidone-based compound featuring a stable lactam core linked to a lipophilic aromatic ether-containing side chain. Its key structural characteristics include a balance of polar amide/lactam functionality and hydrophobic aromatic substitution, resulting in a neutral, amphiphilic molecule within the racetam class.

References

2026. Annotating genomes at increased scale and resolution. Nature reviews. Genetics.
DOI: 10.1038/s41576-026-00937-3

2026. Prepectoral Implant for Immediate Breast Reconstruction after Mastectomy: A Review Article. Indian Journal of Surgical Oncology.
DOI: 10.1007/s13193-025-02512-4

2026. Surgical outcomes and quality of life status after implant pocket conversion from subpectoral to pre-pectoral breast reconstruction. European Journal of Plastic Surgery.
DOI: 10.1007/s00238-026-02390-1