Acetylfentanyl
[CAS# 3258-84-2]

Identification

• Classification: Organic raw materials >> Heterocyclic compound >> Piperidines
• Name: Acetylfentanyl
• Synonyms: N-Phenyl-N-[1-(2-phenylethyl)-4-piperidinyl]-acetamide
• Molecular Formula: C₂₁H₂₆N₂O
• Molecular Weight: 322.44
• CAS Registry Number: 3258-84-2
• EC Number: 642-159-4
• SMILES: CC(=O)N(C1CCN(CC1)CCC2=CC=CC=C2)C3=CC=CC=C3

Properties

• Solubility: Very slightly soluble (0.3 g/L) (25 ºC), Calc.^*
• Density: 1.100±0.06 g/cm³ (20 ºC 760 Torr), Calc.^*
• Melting point: 96-97 ºC^**
• Boiling point: 453.8±38.0 ºC 760 mmHg (Calc.)^*
• Flash point: 183.1±19.1 ºC (Calc.)^*
• Index of refraction: 1.591 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (©1994-2013 ACD/Labs)

^** Janssen, Paul A. J.; FR M2430 1964.

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
Specific target organ toxicity - single exposure	STOT SE	3	H335
Acute toxicity	Acute Tox.	4	H302
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Acute toxicity	Acute Tox.	2	H310
Specific target organ toxicity - single exposure	STOT SE	3	H336
Acute toxicity	Acute Tox.	2	H300
Acute toxicity	Acute Tox.	2	H330

Discovory and Applicatios

Acetylfentanyl is a synthetic opioid analgesic structurally related to fentanyl, differing primarily by the substitution of an acetyl group for the propionyl moiety found in fentanyl. This modification results in a compound with potent μ-opioid receptor agonist activity, although typically estimated to be slightly less potent than fentanyl itself. Like other fentanyl analogs, acetylfentanyl has been associated with central nervous system depression, respiratory failure, and fatal overdose.

First identified in illicit drug markets in the early 2010s, acetylfentanyl gained attention due to a series of fatal intoxications. Unlike pharmaceutical fentanyl, acetylfentanyl has no approved medical use and is classified as a non-medical, recreational opioid. Its emergence as a designer drug reflects attempts to bypass drug regulations while producing substances with similar or near-similar pharmacological effects to controlled opioids.

Chemically, acetylfentanyl retains the core anilidopiperidine scaffold characteristic of fentanyl analogs, with the N-phenethyl group and piperidine ring system largely unchanged. The acetyl substitution, while a relatively small structural change, has significant implications for binding affinity, metabolic stability, and lipophilicity. Acetylfentanyl has been shown in animal studies and receptor binding assays to exhibit high affinity for the μ-opioid receptor, eliciting potent analgesic effects and reinforcing properties.

Acetylfentanyl undergoes hepatic metabolism primarily through N-dealkylation and hydroxylation pathways. Major metabolites include noracetylfentanyl and hydroxyacetylfentanyl, which are typically inactive or exhibit only weak receptor interactions. These metabolites are excreted renally and are often included in toxicological screens used to identify synthetic opioid use.

In forensic toxicology, acetylfentanyl can be detected in biological specimens using advanced analytical methods such as gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Due to its high potency and risk of lethality at low doses, detection of acetylfentanyl is a critical component of opioid surveillance programs and postmortem toxicology investigations.

Legally, acetylfentanyl has been scheduled as a controlled substance in multiple countries under emergency or permanent regulations. In the United States, it is classified as a Schedule I substance, indicating no accepted medical use and a high potential for abuse. Its inclusion in this category was prompted by public health concerns related to its toxicity and involvement in numerous overdose deaths.

Clinically, there are no sanctioned applications of acetylfentanyl, and its pharmacological properties have been studied almost exclusively in the context of illicit use or toxicological evaluation. In cases of overdose, treatment follows protocols used for other potent opioids, with the administration of opioid antagonists such as naloxone. Due to the high receptor affinity and potential for prolonged action, repeated dosing or continuous infusion of naloxone may be required to reverse its effects.

The appearance of acetylfentanyl in street drug supplies often reflects substitution or adulteration of heroin or other opioids. This presents a substantial risk to users unaware of the presence or potency of such substances, contributing to the unpredictability and danger of synthetic opioid exposure. Monitoring and regulation of fentanyl analogs like acetylfentanyl remain a priority for public health agencies and law enforcement.

References

2015. Acetyl Fentanyl, a Novel Fentanyl Analog, Causes 14 Overdose Deaths in Rhode Island, March�May 2013. Journal of Medical Toxicology, 11(4).
DOI: 10.1007/s13181-015-0477-9

2016. Old opioids, new concerns: the case of acetylfentanyl. Forensic Toxicology, 34(2).
DOI: 10.1007/s11419-016-0310-4

2018. Acetyl Fentanyl: Trends and Concentrations in Metro Detroit. Journal of Forensic Sciences, 63(3).
DOI: 10.1111/1556-4029.13840