Acetylfentanyl Hydrochloride
[CAS# 117332-89-5]

Identification

• Classification: Organic raw materials >> Heterocyclic compound >> Piperidines
• Name: Acetylfentanyl Hydrochloride
• Synonyms: N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]acetamide;hydrochloride
• Molecular Formula: C₂₁H₂₇ClN₂O
• Molecular Weight: 358.90
• CAS Registry Number: 117332-89-5
• EC Number: 962-493-7
• SMILES: CC(=O)N(C1CCN(CC1)CCC2=CC=CC=C2)C3=CC=CC=C3.Cl

Safety Data

• Hazard Symbols: GHS06;GHS07 Danger
• Hazard Statements: H301-H311-H331-H336
• Precautionary Statements: P261-P262-P264-P270-P271-P280-P301+P316-P302+P352-P304+P340-P316-P319-P321-P330-P361+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Specific target organ toxicity - single exposure	STOT SE	3	H336
Acute toxicity	Acute Tox.	3	H301
Acute toxicity	Acute Tox.	3	H311
Acute toxicity	Acute Tox.	3	H331

Discovory and Applicatios

Acetylfentanyl hydrochloride is a synthetic opioid compound that belongs to the anilidopiperidine class of analgesics, structurally related to fentanyl. Its discovery is rooted in mid twentieth century pharmaceutical research aimed at developing potent opioid analgesics with rapid onset and predictable pharmacological profiles. During this period, extensive work was conducted on modifications of the fentanyl structure in order to explore how small chemical changes affected analgesic potency, receptor affinity, and safety margins.

Fentanyl itself was first synthesized in 1959 by Paul Janssen and colleagues as part of a systematic program to identify highly potent opioid analgesics suitable for anesthesia. Following this success, numerous analogues were prepared by altering the acyl group attached to the anilide nitrogen or modifying other parts of the molecule. Acetylfentanyl differs from fentanyl by replacement of the propionyl group with an acetyl group. This apparently minor structural change was sufficient to alter pharmacological potency and duration of action, making acetylfentanyl somewhat less potent than fentanyl but still significantly stronger than morphine.

Early investigations of acetylfentanyl were conducted in controlled laboratory settings as part of structure–activity relationship studies. These studies evaluated analgesic activity, respiratory depression, and binding affinity at the μ-opioid receptor. Results demonstrated that acetylfentanyl acts as a strong μ-opioid receptor agonist, producing analgesia and central nervous system depression similar in character to fentanyl, though at higher required doses. At the time of its initial description, acetylfentanyl was not advanced for routine clinical use, as fentanyl and later analogues with more favorable pharmacokinetic properties were preferred for medical applications.

For several decades, acetylfentanyl remained largely a compound of academic interest, referenced mainly in pharmacological literature and patent filings describing fentanyl analogues. Its application shifted markedly in the early twenty first century, when it began to appear outside the pharmaceutical research context. Advances in analytical chemistry and globalized chemical supply chains facilitated the reemergence of previously described opioid analogues, including acetylfentanyl, in nonmedical settings.

The identification of acetylfentanyl hydrochloride in seized drug samples and postmortem toxicology marked its most significant modern application. Forensic laboratories developed validated analytical methods to distinguish acetylfentanyl from fentanyl and other closely related analogues, as small structural differences can produce overlapping mass spectral features. These analytical efforts were critical for accurate attribution of opioid related intoxications and fatalities. Studies documented that acetylfentanyl produces profound respiratory depression consistent with its μ-opioid receptor agonism, and that its potency poses substantial overdose risk, particularly when users are unaware of its presence.

From a regulatory standpoint, the detection of acetylfentanyl contributed to changes in how synthetic opioids are controlled. Rather than addressing each new analogue individually, some jurisdictions adopted broader legislative approaches targeting entire classes of fentanyl related substances. In this context, acetylfentanyl hydrochloride became an example frequently cited in discussions of public health surveillance, early warning systems, and the need for rapid analytical response to emerging opioids.

Scientifically, acetylfentanyl continues to serve as a reference compound in studies of opioid receptor pharmacology and forensic toxicology. Its known structure and well characterized activity allow it to be used for comparison when evaluating newly identified fentanyl analogues. Thus, while acetylfentanyl hydrochloride has no accepted therapeutic application, its discovery and subsequent identification in forensic contexts have had a lasting impact on opioid research, analytical science, and drug control policy.

References

Janssen PAJ, Niemegeers CJE, Dony JGH (1963) The inhibitory effect of fentanyl and other morphine-like analgesics on the warm water induced tail withdrawal reflex in rats. Arzneimittel-Forschung 13 502–507 PMID: 13957426

Higashikawa Y and Suzuki S (2008) Studies on 1-(2-phenethyl)-4-(N-propionylanilino)piperidine (fentanyl) and its related compounds. VI. Structure-analgesic activity relationship for fentanyl, methyl-substituted fentanyls and other analogues. Forensic Toxicology 26(1) 1–5 DOI: 10.1007/s11419-007-0039-1