PENACETIN

Penacetin is a white crystalline organic compound belonging to the acetanilide family, chemically identified as N-(4-ethoxyphenyl)acetamide with the molecular formula C10H13NO2.
Penacetin was formerly incorporated into pain-relieving and fever-reducing medicines, often alongside aspirin and caffeine, before these preparations were withdrawn from several markets because of serious health concerns.
Penacetin is supplied for laboratory research and chemical synthesis, with handling precautions that reflect its carcinogenicity, suspected mutagenicity, and potential to cause allergic skin reactions.

CAS Number: 62-44-2
EC Number: 200-533-0
Molecular Formula: C10H13NO2
Molecular Weight: 179.22 g/mol

Synonyms: Coriforte, BRN 1869238, Acetic acid amide N-(4-ethoxyphenyl)-, Penacetin (Standard), 1-Acetyl-p-phenetidin, AI3-00783, 4-Ethoxy-1-acetylaminobenzene, N-[4-(ethyloxy)phenyl]acetamide, CAS-62-44-2, NCGC00016281-06, Penacetin (p-Acetophenetidide), Penacetine [INN-French], Penacetinum [INN-Latin], 40674-52-0, SMR000752916, SR-01000787183, NSC 7651, EINECS 200-533-0, RCRA waste no. U187, Daprisal, Dasikon, Dolostop, Edrisal, Empiral, Emprazil, Epragen, Fortacyl, Gelonida, Gewodin, Helvagit, Hocophen, Melabon, Melaforte, Pamprin, Paramette, Paratodol, Phenodyne, Pyrroxate, Quadronal, Salgydal, Sanalgine, Saridon, Seranex, Sinedal, Sinutab, Stellacyl, Synalogos, Treupel, Veganine, Anapac, Fenia, Malex, Tacol, Viden, Xaril, Bromo seltzer, Kafa, Phenaphen plus, Robaxisal-ph, Citra-fort, Super Anahist, Dasin ch, Emprazil-C, Coryban-D, Paracetophenetidin, Hjorton'S powder, Acet-p-phenetidin, Thephorin A-C, Buff-A-Comp, Fiorinal, Sinutabs, Acetanilide 4'-ethoxy-, Fenacetin [Czech], RCRA waste number U187, Fenacetin, N-Acetyl-4-ethoxyaniline, Fenacetina [INN-Spanish], N-para-Ethoxyphenylacetamide, CCRIS 496, HSDB 3152, 4-(Acetylamino)phenetole, MFCD00009094, p-Ethoxyanilid kyseliny octove, p-Ethoxyanilid kyseliny octove [Czech]

Penacetin is an organic compound also known as acetophenetidin or N-(4-ethoxyphenyl)acetamide, with the molecular formula C10H13NO2 and a molecular weight of approximately 179.22 g/mol.
Penacetin occurs as a white, odorless crystalline solid and was historically used as an analgesic and antipyretic to relieve pain and reduce fever, often in combination with other medicinal ingredients.

Penacetin-containing medicines were withdrawn from several markets because of serious health concerns, including kidney damage and cancer risks, so its former pharmaceutical functions should be described as historical uses.
Penacetin exerts its pharmacological effect mainly through its metabolite paracetamol (acetaminophen), which is formed in the body after ingestion.

For many years, Penacetin was widely used alone or in combination products for pain relief and fever reduction.
However, Penacetin itself does not possess strong anti-inflammatory activity.

Due to serious safety concerns, including nephrotoxicity, methemoglobinemia, and carcinogenicity, Penacetin has been withdrawn or banned in many countries since the late 20th century.
Today, Penacetin is no longer approved for therapeutic use but may still be encountered in laboratory research, reference standards, and forensic or analytical chemistry applications.

Penacetin is a synthetic organic compound that belongs to the acetanilide class and was historically used as an analgesic and antipyretic to relieve pain and reduce fever. 
Penacetin is chemically known as N-(4-ethoxyphenyl)acetamide and appears as a white crystalline solid with low water solubility and good stability under normal conditions. 

Penacetin acts mainly by inhibiting prostaglandin synthesis in the central nervous system, which contributes to its pain-relieving and fever-reducing effects.
Penacetin was widely used in combination analgesic formulations during the early and mid-20th century, often together with caffeine or aspirin to enhance efficacy. 

Over time, Penacetin was discovered that Penacetin is metabolized in the body to paracetamol (acetaminophen), which is responsible for much of its therapeutic effect. 
This metabolic pathway also produces toxic intermediates that accumulate with prolonged or high-dose use.

Due to strong evidence linking Penacetin to serious adverse effects such as kidney damage, methemoglobinemia, and increased risk of urinary tract cancers, it has been withdrawn or banned for medicinal use in many countries. 
Penacetin is primarily encountered as a pharmaceutical reference standard, analytical reagent, or historical compound in toxicology and pharmacology studies. 

Penacetin may also be classified as hazardous waste in regulatory frameworks because of its carcinogenic potential.
Penacetin is used as an analgesic and antipyretic drug. 

Penacetin is used alone or in combination with aspirin and caffeine for mild to moderate muscle pain relief. 
Penacetin has also been used as a stabilizer for hydrogen peroxide in hair bleaching preparations. 

Uses of Penacetin:
Penacetin was used as an analgesic and fever-reducing drug in both human and veterinary medicine for many years until it was implicated in kidney disease (nephropathy) due to abuse of analgesics and was withdrawn from the market. 
Penacetin also was previously used as a stabilizer for hydrogen peroxide in hair-bleaching preparations.

Penacetin was historically used as an analgesic to relieve pain and as an antipyretic to reduce fever, frequently in combination preparations containing aspirin and caffeine.
Penacetin was also formerly used as a stabilizer for hydrogen peroxide in hair-bleaching preparations.
These applications should be presented as historical uses, since Penacetin-containing medicines were withdrawn from several markets following concerns about kidney damage and cancer risks.

Component of APC tablets, analgesic mixture also containing aspirin and caffeine. 
Penacetin is reasonably anticipated to be a human carcinogen; analgesic mixtures containing Penacetin are listed as known human carcinogens.

Penacetin is a member of the class of acetamides that is acetamide in which one of the hydrogens attached to the nitrogen is substituted by a 4-ethoxyphenyl group. 
Penacetin has a role as a non-narcotic analgesic, a peripheral nervous system drug and a cyclooxygenase 3 inhibitor. 

Penacetin is a member of acetamides and an aromatic ether. 
Penacetin is functionally related to a N-phenylacetamide, a 4-ethoxyaniline and a paracetamol.

Penacetin was historically used as an analgesic and antipyretic for the relief of mild to moderate pain and fever. 
Penacetin was commonly included in compound painkillers together with substances such as caffeine, aspirin, or codeine to enhance therapeutic efficacy. 

These formulations were widely prescribed for headaches, neuralgia, rheumatic pain, and influenza-related fever.
In pharmaceutical science, Penacetin has been used as a reference standard due to its well-defined melting point and crystalline properties. 

Historical pharmaceutical use:
Penacetin was formerly used as an analgesic and antipyretic for the treatment of pain and fever.

Combination drug formulations (historical):
Penacetin was widely included in combination analgesic products together with caffeine and aspirin before being withdrawn for safety reasons.

Laboratory and analytical applications:
Penacetin is currently used as a reference compound in analytical chemistry, pharmaceutical analysis, and method validation studies.

Research and teaching:
Penacetin is used in academic laboratories for educational purposes, including crystallization experiments and studies on drug metabolism.

Forensic and toxicological studies:
Penacetin is applied as a standard in forensic science and toxicology to study drug abuse, adulterants, and metabolic pathways.

Chemical research:
Penacetin is used as a model compound in studies related to acetanilide derivatives and structure–activity relationships.

Note:
Penacetin is no longer approved for medical use in most countries due to its toxicity and carcinogenic risk.

Structure of Penacetin:
Penacetin has the chemical structure of an acetanilide derivative, specifically p-ethoxyacetanilide, in which an ethoxy group is attached to the para position of a benzene ring relative to an acetamide group.
The molecule consists of an aromatic ring that provides planarity and hydrophobic character, an amide functional group capable of hydrogen bonding, and an ethoxy substituent that increases lipophilicity.
This structural arrangement influences Penacetin's metabolic conversion to paracetamol and is closely associated with both its analgesic activity and its known toxicity.

Functions of Penacetin:

Analgesic function:
Penacetin functions to relieve mild to moderate pain by acting centrally after metabolic conversion to paracetamol.

Antipyretic function:
Penacetin reduces elevated body temperature by influencing thermoregulatory centers in the central nervous system.

Prodrug function:
Penacetin acts as a prodrug, with its primary pharmacological activity arising from its metabolism to paracetamol (acetaminophen).

Central nervous system modulation:
Penacetin indirectly affects central pain perception pathways, contributing to its analgesic effect.

Research reference function:
Penacetin functions as a reference and model compound in pharmaceutical, toxicological, and analytical research.

Educational function:
Penacetin is used to demonstrate principles of drug metabolism, toxicity, and structure–activity relationships in academic settings.

Synthesis of Penacetin:
Penacetin is commonly synthesized by first preparing the key intermediate p-phenetidine and then converting it to the acetanilide derivative.
In a typical route, p-nitrophenol is ethylated (or an equivalent p-hydroxy precursor is ethylated) to form p-ethoxynitrobenzene, which is then reduced (e.g., catalytic hydrogenation or metal/acid reduction) to yield p-ethoxyaniline (p-phenetidine).
The final step is an acylation reaction: p-phenetidine is reacted with an acetylating agent such as acetic anhydride (or acetyl chloride) to form the amide, producing Penacetin (p-ethoxyacetanilide), followed by purification typically via crystallization.

Stability and Reactivity of Penacetin:

Chemical stability:
Penacetin is chemically stable under normal ambient conditions.

Reactivity:
Violent reactions may occur with strong oxidizing agents.

Dust hazard:
Finely dispersed dust may present an explosion hazard.

Hazardous decomposition products:
Fire may release carbon oxides and nitrogen oxides.

Handling and Storage of Penacetin:

Safe handling:
Handle under a fume hood, avoiding dust inhalation and direct contact.

Storage conditions:
Keep containers tightly closed in a dry, well-ventilated area.

Access restrictions:
Store locked up or accessible only to authorized personnel.

Storage temperature:
Follow the temperature specified on the product label.

First Aid Measures of Penacetin:

Inhalation:
Move the affected person to fresh air and obtain medical attention.

Skin contact:
Remove contaminated clothing and shoes, wash thoroughly with soap and water, and seek medical attention.

Eye contact:
Rinse immediately with plenty of water for at least 15 minutes, including beneath the eyelids, and obtain medical attention.

Ingestion:
Rinse the mouth with water and seek medical attention.

Notes for physician:
Treat symptomatically.

Firefighting Measures of Penacetin:

Suitable extinguishing media:
Use water spray, foam, dry chemical powder, or carbon dioxide.

Special hazards:
Penacetin is combustible and may release hazardous gases during fire.

Protective equipment:
Firefighters should wear self-contained breathing apparatus and suitable protective clothing.

Environmental precautions:
Prevent contaminated firefighting water from entering surface water or groundwater.

Accidental Release Measures of Penacetin:

Personal precautions:
Isolate the affected area, provide ventilation, and avoid contact or dust inhalation.

Environmental precautions:
Prevent the material from entering drains.

Cleanup methods:
Collect spilled material carefully without generating dust and clean the affected area.

Disposal:
Dispose of collected material according to applicable regulations.

Exposure Controls / Personal Protective Equipment of Penacetin:

Respiratory protection:
Use suitable respiratory protection with a P3 filter when dust is generated.

Hand protection:
Wear appropriate nitrile gloves.

Eye protection:
Wear approved safety glasses.

Skin protection:
Wear protective clothing.

Hygiene measures:
Change contaminated clothing immediately and wash hands and face after handling.

Identifiers of Penacetin:
CAS number: 62-44-2
EC number (EINECS): 200-533-0
Molecular formula: C₁₀H₁₃NO₂
Molecular weight: 179.22 g/mol
Chemical class: Acetanilide derivative
Physical form: Solid
Appearance: White crystalline powder
Odor: Odorless

CAS Number: 62-44-2
Molecular Formula: C10H13NO2
Molecular Weight: 179.22
EINECS Number: 200-533-0

Properties of Penacetin:
Physical state: Solid
Appearance: White crystalline powder
Odor: Odorless
Taste: Slightly bitter
Melting point: Approximately 134–136 °C
Boiling point: Not applicable
Density: Approximately 1.2 g/cm³
Solubility in water: Very slightly soluble
Solubility in organic solvents: Soluble in ethanol, chloroform, acetone; slightly soluble in ether
pH: Not applicable
Vapor pressure: Negligible

Melting point: 133–136 °C (lit.)
Boiling point: 132 °C at 4 mmHg
Density: 1.1248 (rough estimate)
Refractive index: 1.5710
Flash point: 2 °C
Storage temperature: sealed in dry conditions, room temperature
Solubility: chloroform (slightly), methanol (slightly)
Form: powder
pKa: 2.2 (H₂O, uncertain); 3.5 (aqueous acetone, uncertain)
Color: white
Water solubility: 0.076 g/100 mL
Sensitive: hygroscopic
Merck: 14,7204
BRN: 1869238
Stability: stable; incompatible with strong oxidizing agents and strong acids
Cosmetics ingredients functions: light stabilizer
InChIKey: CPJSUEIXXCENMM-UHFFFAOYSA-N
LogP: 1.580