Phenacetin is a synthetic acetanilide derivative chemically known as N-(4-ethoxyphenyl)acetamide or acetophenetidin. It has the molecular formula C10H13NO2, molecular weight 179.22 g/mol, and CAS Number 62-44-2. Phenacetin occurs as a white crystalline solid or crystalline powder and has historically been used as an analgesic and antipyretic compound.
Phenacetin is a small-molecule pharmaceutical substance with a well-defined chemical structure. It has no stereocenters and therefore does not require stereochemical purity testing in the same manner as chiral pharmaceutical APIs. Its chemical properties, melting behavior, solubility and impurity profile can be evaluated using established pharmacopoeial and analytical procedures.
Phenacetin has a molecular weight of 179.22 g/mol and an exact mass of approximately 179.0946 Da. It is described as an odorless, fine white crystalline solid. Pharmacopoeial information describes it as soluble in ethanol (95), slightly soluble in diethyl ether and very slightly soluble in water.
The Japanese Pharmacopoeia specifies a melting point range of 134–137°C, while other authoritative chemical references report values around 134–137.5°C.
Phenacetin has limited aqueous solubility. PubChem reports approximately 766 mg/L at 25°C, while historical pharmaceutical references describe it as very slightly soluble in water.
Phenacetin has established pharmacopoeial quality information. The Japanese Pharmacopoeia specifies that dried Phenacetin contains not less than 98.0% of C10H13NO2. It also specifies loss on drying NMT 0.5% and residue on ignition NMT 0.05%.
Historical USP information cited in PubChem describes USP-grade Phenacetin as containing 98–101% active ingredient on a dried basis, with p-chloroacetanilide NMT 0.03%. Because these criteria are associated with the cited USP-grade specification, the applicable pharmacopoeial edition should be confirmed before using them as the current release specification.
Phenacetin identification and purity can be evaluated through chromatographic and spectroscopic methods. Pharmacopoeial procedures include chemical identification reactions and quantitative assay. The Japanese Pharmacopoeia assay uses titration after hydrolysis and extraction, rather than a conventional HPLC assay.
Important quality attributes include assay, loss on drying, residue on ignition, related substances and specific process-related impurities. In particular, acetanilide and p-chloroacetanilide are relevant impurities for Phenacetin quality control.
The Japanese Pharmacopoeia also includes a test for readily carbonizable substances, demonstrating the importance of controlling colored or readily carbonizable organic contaminants in the material.
Phenacetin is very slightly soluble in water but has substantially higher solubility in certain organic solvents. Historical pharmaceutical data report that approximately 1 g dissolves in 1,310 mL of cold water, 82 mL of boiling water, 15 mL of cold alcohol, and 2.8 mL of boiling alcohol.
The saturated aqueous solution is described as neutral. This should not be interpreted as a formal numerical pH specification for a 1% solution because the pharmacopoeial physical description does not establish such a release limit.
Phenacetin has historical pharmaceutical significance, but it is also recognized as a substance associated with significant toxicological concerns. PubChem identifies Phenacetin as a carcinogenic substance based on the cited regulatory and toxicological classifications.
Accordingly, any commercial handling or use of Phenacetin should follow applicable national regulations, occupational safety requirements and intended-use restrictions. For analytical and research applications, appropriate laboratory controls and safety procedures should be followed.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 0.5% |
| Residue on Ignition | NMT 0.50% |
| pH (1% Solution) | 2.0 – 4.0 |
| Individual Impurity | NMT 0.3% |
| Total Impurities | NMT 0.5% |
| Water Content | NMT 0.5% |
| Melting Point | 134–137°C |