p-Fluorofentany
[CAS# 90736-23-5]

Identification

• Classification: Organic raw materials >> Heterocyclic compound >> Piperidines
• Name: p-Fluorofentany
• Synonyms: 4-Fluorofentanyl; N-(4-fluorophenyl)-N-[1-(2-phenylethyl)piperidin-4-yl]propanamide
• Molecular Formula: C₂₂H₂₇FN₂O
• Molecular Weight: 354.46
• CAS Registry Number: 90736-23-5
• EC Number: 867-478-8
• SMILES: CCC(=O)N(C1CCN(CC1)CCC2=CC=CC=C2)C3=CC=C(C=C3)F

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*
• Boiling point: 479.2±45.0 ºC 760 mmHg (Calc.)^*
• Flash point: 243.6±28.7 ºC (Calc.)^*
• Index of refraction: 1.575 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS06 Danger
• Hazard Statements: H300-H300-H310-H330
• Precautionary Statements: P260-P262-P264-P270-P271-P280-P284-P301+P316-P302+P352-P304+P340-P316-P320-P321-P330-P361+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	2	H310
Acute toxicity	Acute Tox.	2	H300
Acute toxicity	Acute Tox.	2	H330

• Controlled Substance: DEA Drug Code Number: 9812

Discovory and Applicatios

p-Fluorofentanyl is a synthetic opioid analgesic structurally related to fentanyl, characterized by the substitution of a fluorine atom at the para position of the phenyl ring attached to the anilide moiety. This minor structural modification results in a compound that retains high affinity for the μ-opioid receptor, the principal mediator of opioid analgesia and respiratory depression. As with other fentanyl analogs, p-fluorofentanyl has been developed in the context of structure-activity relationship studies aimed at understanding how substituent variation affects potency, receptor selectivity, and pharmacological effects.

The incorporation of a fluorine atom at the para position of the aromatic ring does not significantly alter the overall lipophilicity or size of the molecule, but it can influence electronic distribution and metabolic stability. Fluorine is known to increase the metabolic resistance of aromatic compounds, potentially leading to prolonged duration of action. In vitro binding studies and in vivo animal assays have shown that p-fluorofentanyl retains high μ-receptor agonist activity, with potency similar to or moderately higher than fentanyl, depending on the assay and species.

p-Fluorofentanyl has no accepted medical use and is not approved for therapeutic applications. It has emerged primarily as a component of illicit synthetic opioid formulations. In recent years, law enforcement and toxicology laboratories have identified p-fluorofentanyl in seized drug samples and in biological specimens from overdose cases. Its presence is often associated with counterfeit tablets or powder mixtures that also contain other fentanyl analogs or adulterants. The clandestine synthesis of this compound mirrors the synthetic routes of fentanyl itself, involving modification of the N-phenyl-N-piperidinylpropanamide core.

Pharmacologically, p-fluorofentanyl acts as a full agonist at the μ-opioid receptor, producing typical opioid effects such as profound analgesia, euphoria, sedation, miosis, and respiratory depression. Like other potent opioids, it can cause rapid and severe respiratory compromise leading to death, especially when taken in unknown quantities or mixed with other central nervous system depressants. The onset and duration of action are presumed to be similar to fentanyl, although specific pharmacokinetic data are lacking due to the compound’s classification and limited legitimate research use.

Detection of p-fluorofentanyl in forensic and clinical settings typically relies on advanced analytical techniques such as liquid chromatography-tandem mass spectrometry (LC-MS/MS) or gas chromatography-mass spectrometry (GC-MS). These methods are essential for distinguishing p-fluorofentanyl from other fentanyl analogs, especially given the subtle structural differences that influence toxicity but may be overlooked by immunoassay-based screening tests.

The public health risk posed by p-fluorofentanyl is significant due to its high potency and unpredictability in illicit drug preparations. Users may unknowingly consume the compound, leading to accidental overdose. The use of naloxone, an opioid antagonist, remains the primary intervention in cases of p-fluorofentanyl overdose, although multiple or high doses may be required depending on the severity of respiratory depression and the amount of opioid involved.

In response to its detection in the illicit drug supply, regulatory bodies have moved to control p-fluorofentanyl as a Schedule I substance or equivalent classification in various jurisdictions. These regulatory actions aim to reduce availability and mitigate harm associated with synthetic opioids. Nonetheless, the compound continues to appear in toxicology reports and emergency medical cases, reflecting ongoing challenges in addressing the evolving nature of synthetic opioid proliferation.

The emergence of p-fluorofentanyl highlights the adaptability of clandestine laboratories in producing new fentanyl analogs through minor chemical modifications. Its pharmacological profile and dangers are consistent with other synthetic opioids, underscoring the importance of continued surveillance, education, and regulatory enforcement to manage the risks associated with these substances.

References

2000. Interaction of p-fluorofentanyl on cloned human opioid receptors and exploration of the role of Trp-318 and His-319 in mu-opioid receptor selectivity. The Journal of Pharmacology and Experimental Therapeutics, 294(3).
DOI: 10.1016/s0022-3565(24)39167-0

2003. Seizure of illicitly produced para-fluorofentanyl: quantitative analysis of the content of capsules and tablets. Journal of Pharmaceutical and Biomedical Analysis, 31(3).
DOI: 10.1016/s0731-7085(02)00684-2

2024. A quantitative LC-MS/MS analysis of Xylazine, p-Fluorofentanyl, Fentanyl and Fentanyl-Related compounds in postmortem blood. Journal of Chromatography B, 1236.
DOI: 10.1016/j.jchromb.2024.124059