3,4-Dihydroxybenzoic acid
[CAS# 99-50-3]

Identification

• Classification: Biochemical >> Chinese herbal medicine ingredients
• Name: 3,4-Dihydroxybenzoic acid
• Synonyms: Protocatechuic acid
• Molecular Formula: C₇H₆O₄
• Molecular Weight: 154.12
• CAS Registry Number: 99-50-3
• EC Number: 202-760-0
• SMILES: C1=CC(=C(C=C1C(=O)O)O)O

Properties

• Density: 1.6±0.1 g/cm³, Calc.^*
• Melting point: 197-200 °C (Expl.)
• Index of Refraction: 1.671, Calc.^*
• Boiling Point: 410.7±35.0 °C (760 mmHg), Calc.^*
• Flash Point: 216.3±22.4 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07;GHS09 Warning
• Risk Statements: H315-H319-H335-H411
• Safety Statements: P261-P264-P264+P265-P271-P273-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P391-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411
Eye irritation	Eye Irrit.	2A	H319

Discovery and Applications

3,4-Dihydroxybenzoic acid, also known as protocatechuic acid, is a naturally occurring compound belonging to the class of hydroxybenzoic acids. It is an important intermediate in the metabolism of certain phenolic compounds and is widely distributed in various plants, particularly in fruits, vegetables, and herbs. This compound has been studied for its potential biological activities and applications in food, medicine, and environmental science.

The discovery of 3,4-dihydroxybenzoic acid dates back to the early 20th century when it was first identified as a component of plant extracts. It is primarily formed through the degradation of larger aromatic compounds, such as lignin, and is a key product in the breakdown of certain polyphenolic compounds. It can also be found as a metabolite of caffeic acid and is present in the metabolic pathways of various plant species. The compound’s structure consists of a benzene ring with two hydroxyl groups attached to the 3 and 4 positions, which contribute to its antioxidant properties.

3,4-Dihydroxybenzoic acid is widely studied for its potential antioxidant, anti-inflammatory, and antimicrobial activities. Its ability to scavenge free radicals and protect cells from oxidative stress has made it a subject of interest in the development of nutraceuticals and pharmaceuticals aimed at combating oxidative damage, which is a contributor to aging, cancer, and cardiovascular diseases. As an antioxidant, it helps neutralize reactive oxygen species (ROS), preventing cellular damage and supporting overall health.

In addition to its antioxidant properties, 3,4-dihydroxybenzoic acid has demonstrated anti-inflammatory effects in various experimental models. Chronic inflammation is a key factor in the pathogenesis of several diseases, including arthritis, cardiovascular diseases, and neurodegenerative disorders. Studies have shown that protocatechuic acid can inhibit the production of pro-inflammatory cytokines, thus potentially reducing inflammation and alleviating the symptoms associated with inflammatory diseases. This has led to investigations into its potential use as a therapeutic agent for conditions such as rheumatoid arthritis and inflammatory bowel diseases.

The compound has also been shown to possess antimicrobial properties, making it a potential candidate for use in food preservation and natural antimicrobial formulations. In laboratory studies, 3,4-dihydroxybenzoic acid has demonstrated activity against various bacterial and fungal strains, including some pathogens that are resistant to conventional antibiotics. This feature has prompted interest in its incorporation into natural preservatives for food products, as well as its potential in topical antimicrobial treatments.

In the food industry, 3,4-dihydroxybenzoic acid is valued for its contribution to the flavor profile of certain fruits and beverages. It is found in relatively high concentrations in the seeds and skins of fruits such as strawberries, apples, and grapes, where it contributes to the overall antioxidant content. Additionally, its presence in plant-based beverages and herbal teas contributes to the health-promoting qualities associated with these products. As a result, 3,4-dihydroxybenzoic acid is increasingly recognized as a functional ingredient in health-focused food products.

In environmental science, the compound has potential applications in bioremediation, particularly in the degradation of environmental pollutants. The compound is involved in the breakdown of lignin and other aromatic compounds, which are often resistant to biodegradation. Research has suggested that 3,4-dihydroxybenzoic acid may play a role in the microbial degradation of such pollutants, making it a potential candidate for use in the treatment of contaminated soils and water.

3,4-Dihydroxybenzoic acid is also gaining attention in the field of cosmetics. Its antioxidant and anti-inflammatory properties make it an appealing ingredient in skin care products aimed at reducing signs of aging, improving skin texture, and protecting against environmental stressors. Due to its ability to neutralize free radicals, it may help reduce oxidative damage to the skin, promoting a healthier and more youthful appearance.

In summary, 3,4-dihydroxybenzoic acid is a versatile compound with a broad range of potential applications in food, medicine, and environmental science. Its discovery as an intermediate in plant metabolism has led to further investigations into its antioxidant, anti-inflammatory, and antimicrobial properties. With its potential health benefits and environmental applications, this compound continues to be an area of active research.

References

Mazurek, J., Dova, E. & Helmond, R., 2007. 3,4-Dihydroxybenzoic acid acetonitrile solvate at 120 K. Acta Crystallographica Section E: Structure Reports Online, E63, o3289.
DOI: 10.1107/S160053680702987X

Nematollahi, D. & Rafiee, M., 2005. Diversity in electrochemical oxidation of dihydroxybenzoic acids in the presence of acetylacetone . A green method for synthesis of new benzofuran derivatives. Green Chemistry, 7, 644.
DOI: 10.1039/B503408F

Grzelak-Błaszczyk, K., et al., 2020. Protocatechuic acid and quercetin glucosides in onions attenuate changes induced by high fat diet in rats. Food & Function, 11, 3597.
DOI: 10.1039/C9FO02633A