437-38-7

Basic information

• Product Name: FENTANYL
• Synonyms: FENTANYL;FENTANYL BASE;1-(2-Phenylethyl)-4-(N-propananilido)piperidine;1-Phenethyl-4-(N-Phenylpropionamido)piperidine;1-Phenethyl-4-N-propionylanilinopiperidine;Fentanest;Fentanil;fentanila
• CAS NO: 437-38-7
• Molecular Formula: C₂₂H₂₈N₂O
• Molecular Weight: 336.47
• EINECS: 207-113-6
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 437-38-7.mol
• Article Data: 21

Chemical Properties

• Melting Point: 83-84°C
• Boiling Point: 466℃
• Flash Point: 186℃
• Appearance: Pale brown solid
• Density: 1.087
• Refractive Index: 1.6500 (estimate)
• Storage Temp.: Controlled Substance, -20°C Freezer
• Solubility: Practically insoluble in water, freely soluble in ethanol (96 per cent) and in methanol
• PKA: 8.4(at 25℃)
• Water Solubility: 0.2g/L(25 oC)
• CAS DataBase Reference: FENTANYL(CAS DataBase Reference)
• NIST Chemistry Reference: FENTANYL(437-38-7)
• EPA Substance Registry System: FENTANYL(437-38-7)

Safety Data

• Hazard Codes: F,T
• Statements: 11-23/25-36/38-39/23/24/25-23/24/25
• Safety Statements: 16-24-45-36/37-7
• RIDADR: 1544
• WGK Germany: 2
• RTECS: UE5550000
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 437-38-7(Hazardous Substances Data)

Usage

Description

Fentanyl is a powerful synthetic opioid that is approximately 80-100 times more potent than morphine in acute pain management. It is characterized by its high lipophilicity, rapid onset, and short duration of action. Due to its high first-pass metabolism, it is not administered orally and is available in various preparations for parenteral, transdermal, and transmucosal administration.

Uses

Used in Pain Management:
Fentanyl is used as an analgesic for the management of acute and chronic pain. It is particularly effective in cases where other opioids are not sufficient or when rapid pain relief is required.
Used in Anesthesia:
Fentanyl is used as an adjunct in anesthesia to provide analgesia and sedation during surgical procedures. Its rapid onset and short duration of action make it an ideal choice for this application.
Used in Palliative Care:
Fentanyl is used in palliative care to manage severe pain in patients with terminal illnesses, such as cancer. It can be administered through transdermal patches, providing a slow and steady release of the drug over an extended period.
Used in Breakthrough Pain:
Fentanyl is used as a treatment for breakthrough pain, which is a sudden increase in pain that occurs despite ongoing pain management. New buccal/transmucosal preparations have been developed for rapid-onset breakthrough pain, aiming to provide relief within approximately 10 minutes.
Used in Drug Delivery Systems:
Fentanyl's lipophilic nature and large volume of distribution make it an ideal candidate for drug delivery systems. Various formulations, such as transdermal patches and buccal tablets, have been developed to improve its bioavailability and therapeutic outcomes.

Originator

Fentanyl,Janssen,W. Germany,1963

Manufacturing Process

To the stirred solution of 5 parts of N-(4-piperidyl)propionanilide, 6.85 parts sodium carbonate, 0.05 part potassium iodide in 120 parts hexone is added portionwise a solution of 3.8 parts β-phenylethyl chloride in 24 parts 4- methyl-2-pentanone. The mixture is stirred and refluxed for 27 hours. The reaction mixture is filtered while hot, and the filtrate is evaporated. The oily residue is dissolved in 160 parts diisopropyl ether and the solution is filtered several times until clear, then concentrated to a volume of about 70 parts. The residue is then cooled for about 2 hours at temperatures near 0°C to yield N- [1-(β-phenylethyl)-4-piperidyl]propionanilide, melting at about 83° to 84°C as described in US Patent 3,141,823.The starting material is prepared by reacting 1-benzyl-4-piperidone with aniline, reducing the condensation product with lithium aluminum hydride, reacting the product thus obtained with propionic anhydride, then hydrogen.

Therapeutic Function

Narcotic analgesic

Hazard

Toxic.

Clinical Use

Fentanyl (Sublimaze) and its related phenylpiperidine derivatives are extremely potent drugs.They are used as adjuncts to anesthesia, and fentanyl may be given transdermally as an analgesic and as an oral lozenge for the induction of anesthesia, especially in children who may become anxious if given IV anesthesia. Fentanyl is 80 to 100 times as potent as morphine. Sufentanil (Sufenta) is 500- to 1,000-fold more potent than morphine, while alfentanil (Alfenta) is approximately 20 times more potent than morphine. Their onset of action is usually less than 20 minutes after administration. Dosage is determined by the lean body mass of the patient, since the drugs are lipophilic and tend to get trapped in body fat, which acts as a reservoir, prolonging their half-life. In addition, redistribution of the drugs from the brain to fat stores leads to a rapid offset of action. Droperidol, a neuroleptic agent, is generally administered in combination with fentanyl for IV anesthesia. Fentanyl transdermal patches are available for analgesia in chronic pain and for postsurgical patients. The use of the patch is contraindicated, however, for patients immediately after surgery because of the profound respiratory depression associated with its use. The patches must be removed and replaced every 3 days. The onset of action of transdermal fentanyl is slower than that of oral morphine. Thus, patients may require the use of oral analgesics until therapeutic levels of fentanyl are achieved. Fentanyl lozenges have been used to induce anesthesia in children and to reduce pain associated with diagnostic tests or cancer in adult patients. However, all of the adverse side effects associated with morphine are produced with far greater intensity, but shorter duration, by fentanyl in the patch, the lozenge, or IV administration. Given the abuse liability of fentanyl, controversy exists as to the ethics of marketing a lollipop lozenge form. Sufentanil is much more potent than fentanyl and is indicated specifically for long neurosurgical procedures. In such patients, sufentanil maintains anesthesia over a long period when myocardial and cerebral oxygen balance are critical.

Side effects

In addition to all of the adverse effects and contraindications previously described for morphine, the following contraindications apply specifically to these drugs. They are contraindicated in pregnant women because of their potential teratogenic effects. They also can cause respiratory depression in the mother, which reduces oxygenation of fetal blood, and in the newborn; the incidence of sudden infant death syndrome (SIDS) in the newborn is also increased. Cardiac patients need to be monitored closely when receiving these drugs because of their bradycardiac effects (which can lead to ectopic arrhythmias), and hypotensive effects resulting from prolonged vasodilation. In addition, the drugs stiffen the chest wall musculature, an effect reversed by naloxone.

Safety Profile

Poison by intraperitoneal routes. Human systemic effects by intravenous route: somnolence, respiratory depression. When heated to decomposition it emits toxic fumes of NOx.

Drug interactions

Potentially hazardous interactions with other drugs Antibacterials: metabolism increased by rifampicin. Antidepressants: possible CNS excitation or depression (hypertension or hypotension) in patients also receiving MAOIs (including moclobemide) - avoid concomitant use; possibly increased sedative effects with tricyclics. Antifungals: concentration increased by triazoles. Antihistamines: increased sedative effects with sedating antihistamines. Antipsychotics: enhanced hypotensive and sedative effects. Antivirals: concentration increased by ritonavir; increased risk of ventricular arrhythmias with saquinavir - avoid. Cytotoxics: use crizotinib with caution. Dopaminergics: avoid with selegiline. Sodium oxybate: enhanced effect of sodium oxybate - avoid concomitant use

Metabolism

Fentanyl is metabolised in the liver by N-dealkylation and hydroxylation via the cytochrome P450 isoenzyme CYP3A4. Metabolites and some unchanged drug are excreted mainly in the urine. The short duration of action is probably due to rapid redistribution into the tissues rather than metabolism and excretion. The relatively longer elimination half-life reflects slower release from tissue depots.The main metabolites of fentanyl, which are excreted in the urine, have been identified as 4-N-(N-propionylanilino) piperidine and 4-N-(Nhydroxypropionylanilino) piperidine; 1-(2-phenethyl)- 4-N-(N-hydroxypropionylanilino) piperidine is a minor metabolite. Fentanyl has no active or toxic metabolites.

Upstream product

• 57958-48-2 N-(1-phenethylpiperidin-4-ylidene)aniline 
• 39742-60-4 1-(2-phenylethyl)-4-piperidinone 
• 79-03-8 propionyl chloride 
• 62-53-3 aniline 
• 622-24-2 2-phenylethyl chloride 
• 1609-66-1 Norfentanyl 
• 41979-39-9 4-piperidone hydrochloride 
• 122-78-1 phenylacetaldehyde 
• 74-85-1 ethene 
• 201230-82-2 carbon monoxide 
• 21409-26-7 (1-Phenethyl-piperidin-4-yl)-phenyl-amine 
• 103-63-9 1-phenyl-2-bromoethane 
• 24775-76-6 4-anilino-N-(phenethyl)-4-piperidine bis hydrochloride 
• 1474-02-8 N-(1-benzyl-4-piperidinyl)-N-phenylpropionamide 

Downstream Products

• 1443-54-5 fentanyl hydrochloride 
• 1254229-85-0 N-([2-⁽²⁾H]-1-(2-phenylethyl)-4-piperidinyl)aniline 
• 1254229-86-1 C₂₂H₂₇⁽²⁾HN₂O 
• 1863-07-6 fentanyl citrate 
• 1195983-47-1 Fentanyl methiodide 
• 85893-37-4 fentanyl N-oxide 
• 122861-38-5 N-<1-(2-phenylethyl)-4-piperidyl>-N-phenylthiopropanamide 

Relevant articles and documents

A structural study of fentanyl by DFT calculations, NMR and IR spectroscopy

N-(1-(2-phenethyl)-4-piperidinyl-N-phenyl-propanamide (fentanyl) is synthesized and characterized by FT-IR, 1H NMR, 13C NMR, mass spectroscopy and elemental analyses. The geometry optimization is performed using the B3LYP and M06 density functionals with 6-311?+?G(d) and 6-311++G(d,p) basis sets. The complete assignments are performed on the basis of the potential energy distribution (PED) of the all vibrational modes. Almost a nice correlation is found between the calculated 13C chemical shifts and experimental data. The frontier molecular orbitals and molecular electrostatic potential of fentanyl are also obtained.

Metabolism of fentanyl and acetylfentanyl in human-induced pluripotent stem cell-derived hepatocytes

To evaluate the capability of human-induced pluripotent stem cell-derived hepatocytes (h-iPS-HEP) in drug metabolism, the profiles of the metabolites of fentanyl, a powerful synthetic opioid, and acetylfentanyl, an N-acetyl analog of fentanyl, in the cells were determined and analyzed. Commercially available h-iPSHEP were incubated with fentanyl or acetylfentanyl for 24 or 48 h. After enzymatic hydrolysis, the medium was deproteinized with acetonitrile, then analyzed by LC/MS. Desphenethylated metabolites and some hydroxylated metabolites, including 4′-hydroxy-fentanyl and β-hydroxy-fentanyl, were detected as metabolites of fentanyl and acetylfentanyl in the medium. The main metabolite of fentanyl with h-iPS-HEP was the desphenethylated metabolite, which was in agreement with in vivo results. These results suggest that h-iPSHEP may be useful as a tool for investigating drug metabolism.

Palladium-catalyzed hydroaminocarbonylation of alkenes with amines promoted by weak acid

The weak acid has been identified as an efficient basicity-mask to overcome the basicity barrier imparted by aliphatic amines in the Pd-catalyzed hydroaminocarbonylation, which enables both aromatic and aliphatic amines to be applicable in the palladium-catalyzed hydroaminocarbonylation reaction. Notably, by using this protocol, the marketed herbicide of Propanil and drug of Fentanyl could be easily obtained in a one-pot manner.