Phenacetin
[CAS# 62-44-2]

Identification

• Classification: Organic raw materials >> Amino compound >> Amide compound
• Name: Phenacetin
• Synonyms: 4'-Ethoxyacetanilide; 4-Acetophenetidine
• Molecular Formula: C₁₀H₁₃NO₂
• Molecular Weight: 179.22
• CAS Registry Number: 62-44-2
• EC Number: 200-533-0
• SMILES: CCOC1=CC=C(C=C1)NC(=O)C

Properties

• Melting point: 133-138 °C
• Water solubility: 0.076 g/100 mL
• Flash point: 149 °C

Safety Data

• Hazard Symbols: GHS07;GHS08 Danger
• Risk Statements: H302-H350
• Safety Statements: P203-P264-P270-P280-P301+P317-P318-P330-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Carcinogenicity	Carc.	1B	H350
Carcinogenicity	Carc.	1A	H350
Germ cell mutagenicity	Muta.	2	H341
Acute toxicity	Acute Tox.	4	H312
Acute toxicity	Acute Tox.	4	H332
Skin sensitization	Skin Sens.	1	H317

Discovery and Applications

Phenacetin, a widely used analgesic and antipyretic drug, was first synthesized in 1878 by Harmon Northrop Morse. Derived from p-phenetidine, phenacetin's structure was confirmed through chemical analysis and testing. By 1887, it was introduced into the market by Bayer and quickly became popular due to its effectiveness in reducing pain and fever. Its chemical composition and pharmacological properties have made it a significant compound in medicinal chemistry.

Phenacetin was primarily used to treat mild to moderate pain, such as headaches, toothaches, and menstrual cramps. Its antipyretic properties also made it effective in reducing fever. For many years, it was a common ingredient in over-the-counter pain relief medications and was often combined with other analgesics like aspirin or caffeine to enhance its effects.

Phenacetin was frequently used in combination drugs, such as APC (aspirin, phenacetin, and caffeine) tablets, which were popular for treating pain and inflammation. These combinations provided synergistic effects, improving the overall efficacy of pain relief medications.

Phenacetin's popularity in the early 20th century contributed significantly to the development of the pharmaceutical industry. It paved the way for the synthesis and marketing of other acetaminophen derivatives and similar compounds. Its widespread use in the past highlights the evolution of pain management practices over the years.

Despite its effectiveness, phenacetin was found to have serious side effects, including kidney damage and an increased risk of certain cancers. These findings led to its gradual withdrawal from the market in many countries during the 1970s and 1980s. Today, phenacetin is no longer used in medical treatments due to its adverse effects, but its role in the history of pharmaceuticals remains significant.

While phenacetin is no longer used therapeutically, its chemical structure and pharmacological profile continue to be of interest in research. Studies on phenacetin have provided valuable insights into drug metabolism, mechanisms of action, and the development of safer analgesic compounds.

References

1979. The Morphologic Diagnosis of Analgesic (Phenacetin) Abuse. Pathology - Research and Practice.
DOI: 10.1016/s0344-0338(79)80094-1

1986. N-Acetyltransferase multiplicity and the bioactivation of N-arylhydroxamic acids by hamster hepatic and intestinal enzymes. Carcinogenesis, 7(5).
DOI: 10.1093/carcin/7.5.697

1991. An epidemiologic study of abuse of analgesic drugs. Effects of phenacetin and salicylate on mortality and cardiovascular morbidity (1968 to 1987). The New England Journal of Medicine, 324(3).
DOI: 10.1056/nejm199101173240304