p-Hydroxyacetophenone (4-Hydroxyacetophenone)
p-Hydroxyacetophenone: Structure, Properties, and Applications
1. Introduction
p-Hydroxyacetophenone (4-hydroxyacetophenone, p-HAP) is an aromatic organic compound belonging to the class of substituted acetophenones. Its molecular formula is C₈H₈O₂, with a hydroxyl group (-OH) in the para position relative to the acetyl group. This compound is widely used in the pharmaceutical, cosmetic, and flavor industries due to its antioxidant properties, pleasant odor, and antimicrobial activity.
2. Chemical Structure and Nomenclature
IUPAC name: 1-(4-Hydroxyphenyl)ethan-1-one
Molecular formula: C₈H₈O₂
Molecular weight: 136.15 g/mol
CAS number: 99-93-4
EC number: 202-802-8
Synonyms: 4-Hydroxyacetophenone, para-hydroxyacetophenone, p-acetylphenol, 4-acetylphenol, p-hydroxyphenyl methyl ketone
Appearance: White to off-white crystalline powder
3. Physicochemical Properties
Melting point: 109–112°C
Boiling point: 147–148°C at 3 mmHg
Solubility: Slightly soluble in water (4.1 g/L at 20°C); soluble in ethanol, methanol, acetone, and other organic solvents
pKa: 8.05 (phenolic OH)
Log P: 1.33
Vapor pressure: 0.00124 mmHg at 25°C
Density: 1.109 g/cm³ at 20°C
4. Synthesis Methods
Friedel-Crafts acylation: Phenol is protected (as methyl ether), then acetylated with acetyl chloride in the presence of Lewis acid catalysts (AlCl₃), followed by deprotection.
Other methods: Oxidation or conversion of suitable intermediates with para-substituted phenols.
5. Applications
Pharmaceuticals: Used as an intermediate in the synthesis of analgesics, antibacterial, and antifungal agents. Some derivatives exhibit anti-inflammatory properties.
Cosmetics and personal care: Used as an antioxidant additive and fragrance component in creams, lotions, and perfumes. May also act as a mild preservative, slowing oxidative degradation.
Flavorings: Imparts sweet, floral notes at low concentrations; used in flavor compositions.
Polymers and coatings: Acts as a stabilizer, protecting materials from light and oxidative damage.
6. Biological Activity
Antioxidant: The para-hydroxyl group participates in free radical scavenging, providing antioxidant protection.
Antimicrobial: Some derivatives inhibit bacterial and fungal growth.
Anti-inflammatory: Studies suggest potential for reducing pro-inflammatory mediators; further research is needed.
7. Safety and Toxicology
Acute toxicity: Relatively low toxicity; oral LD₅₀ in rats is >4000 mg/kg.
Irritation: May cause skin and eye irritation at high concentrations; protective equipment recommended.
Allergenic potential: Low; however, as a phenolic compound, individual hypersensitivity is possible.
Environmental aspects: Biodegradable; minimal environmental impact when properly disposed of.
8. Regulatory Status
Approved for use in cosmetics in the EU (CosIng) and US. Listed in EINECS and TSCA inventories. For pharmaceutical use, purity and impurity specifications apply.
9. Research and Development Prospects
New drug derivatives: Exploration of novel anti-inflammatory and antibacterial agents based on the p-hydroxyacetophenone scaffold.
Functional materials: Use as an antioxidant additive in polymers, composites, and innovative coatings.
Green chemistry: Development of biotechnological production methods from plant sources or microbial cultures.
10. Conclusion
p-Hydroxyacetophenone (CAS 99-93-4) is a versatile aromatic compound with valuable antioxidant, antimicrobial, and fragrance properties. Its applications span pharmaceuticals, cosmetics, flavorings, and materials science. While generally safe at recommended concentrations, standard safety precautions should be observed. Ongoing research continues to explore new derivatives and applications for this promising compound.