N-Acetylcaprolactam
[CAS# 1888-91-1]

Identification

• Classification: Chemical reagent >> Organic reagent >> Amide
• Name: N-Acetylcaprolactam
• Synonyms: 1-Acetylhexahydro-2H-azepin-2-one
• Molecular Formula: C₈H₁₃NO₂
• Molecular Weight: 155.19
• CAS Registry Number: 1888-91-1
• EC Number: 217-565-6
• SMILES: CC(=O)N1CCCCCC1=O

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*, 1.094 g/mL (Expl.)
• Boiling point: 242.1 ºC 760 mmHg (Calc.)^*, 262.6 - 263.9 ºC (Expl.)
• Flash point: 122.2±11.1 ºC (Calc.)^*, 122 ºC (Expl.)
• Index of refraction: 1.479 (Calc.)^*, 1.489 (Expl.)

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

Safety Data

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

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Eye irritation	Eye Irrit.	2	H319
Acute toxicity	Acute Tox.	4	H302
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335

Discovory and Applicatios

N-Acetylcaprolactam is an organic compound derived from ε-caprolactam, a seven-membered lactam ring that is best known as the monomer for the production of Nylon-6. In N-Acetylcaprolactam, the nitrogen atom of the lactam ring is modified by the addition of an acetyl group, forming an N-substituted lactam. Its molecular formula is C₈H₁₃NO₂, and its structure consists of a six-carbon cyclic amide ring with an N-acetyl substituent, which affects both its physical properties and reactivity compared to unsubstituted caprolactam.

The compound was first synthesized as part of research into lactam derivatives, aiming to explore structural analogs of caprolactam that might exhibit different physicochemical and biological characteristics. The N-acetylation of caprolactam was achieved through a standard acetylation reaction involving acetic anhydride or acetyl chloride in the presence of a base or acid catalyst. This modification results in a molecule with altered hydrogen bonding capabilities, as the acetyl group removes the free N-H bond typically present in caprolactam, making it less prone to polymerization.

One of the earliest and most explored areas of application for N-Acetylcaprolactam has been in polymer science, particularly in the context of modifying polyamide synthesis. While caprolactam undergoes ring-opening polymerization to form Nylon-6, the N-acetylated form is inactive toward such polymerization under standard conditions. However, it has been investigated as a chain stopper or as a model compound for understanding the kinetics and mechanism of polymerization processes. Its inertness toward polymerization makes it valuable in controlling molecular weight and end-group functionality in polymer production.

In addition to polymer chemistry, N-Acetylcaprolactam has been evaluated for its potential as a pharmaceutical intermediate. The caprolactam ring is a common motif in medicinal chemistry, and N-substituted analogs such as N-Acetylcaprolactam have been studied for their potential biological activities, including antimicrobial and enzyme-inhibitory effects. Although N-Acetylcaprolactam itself is not widely used as an active pharmaceutical ingredient, it has served as a building block or reference compound in the synthesis and study of bioactive lactams.

In chemical research, N-Acetylcaprolactam has also been utilized to model the behavior of amide bonds and to probe intramolecular hydrogen bonding and conformational dynamics in lactam systems. The presence of both the lactam carbonyl and the acetyl carbonyl groups provides a framework for studying dipole interactions and resonance stabilization in amide derivatives. These properties are particularly useful in the design of peptidomimetics and other synthetic analogs of biological molecules.

N-Acetylcaprolactam is typically a crystalline solid at room temperature and exhibits moderate solubility in common organic solvents such as ethanol, acetone, and dichloromethane. It is relatively stable under ambient conditions but may undergo hydrolysis under strongly acidic or basic environments, cleaving the acetyl group or opening the lactam ring. These degradation pathways have been studied to assess the compound’s stability in various chemical environments.

Its utility in multiple domains, including polymer chemistry, materials science, and chemical biology, highlights the importance of N-Acetylcaprolactam as a functionalized lactam with distinct chemical behavior from its parent compound. The selective modification at the nitrogen site opens avenues for the design of novel molecules with tailored properties, contributing to both fundamental chemical understanding and applied research.

References

1980. N-acetyl-epsilon-aminocaproic acid. IV. Hydrolysis of N-acetyl-epsilon-caprolactam. Pharmaceutical Chemistry Journal, 14(1).
DOI: 10.1007/bf00765612

1981. Induction of differentiation of leukemia cells in vitro by N-substituted amides, lactams, and 2-pyridones. Journal of Medicinal Chemistry, 24(9).
URL: https://pubmed.ncbi.nlm.nih.gov/6945436

1982. Polarizability anisotropy and conformation of some imides. Bulletin of the Academy of Sciences of the USSR, Division of chemical science, 31(11).
DOI: 10.1007/bf00958416