Methylparaben
[CAS# 99-76-3]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyridine compound >> Pyridine derivative
• Name: Methylparaben
• Synonyms: Methyl paraben; Methyl p-hydroxybenzoate; 4-(Methoxycarbonyl)phenol; 4-Hydroxybenzoic acid methyl ester; 4-(Carbomethoxy)phenol; Methyl Parasept; Methyl Butex; Methaben; Metaben; Methyl 4-hydroxybenzoate
• Molecular Formula: C₈H₈O₃
• Molecular Weight: 152.15
• CAS Registry Number: 99-76-3
• EC Number: 202-785-7
• FEMA: 2710
• SMILES: COC(=O)C1=CC=C(C=C1)O

Properties

• Density: 1.2±0.1 g/cm³, Calc.^*
• Melting point: 125-128 °C
• Index of Refraction: 1.547, Calc.^*
• Boiling Point: 265.5±13.0 °C (760 mmHg), Calc.^*, 280 °C (decomp.)
• Flash Point: 116.4±12.6 °C,

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-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	3	H412
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411
Serious eye damage	Eye Dam.	1	H318
Skin sensitization	Skin Sens.	1	H317
Germ cell mutagenicity	Muta.	2	H341
Acute toxicity	Acute Tox.	4	H302
Respiratory sensitization	Resp. Sens.	1	H334
Eye irritation	Eye Irrit.	2A	H319
Specific target organ toxicity - single exposure	STOT SE	3	H336

Discovery and Applications

Methylparaben, or para-hydroxybenzoic acid methyl ester, is a widely used organic compound classified as a paraben. It is recognized for its role as a preservative in various products, including cosmetics, pharmaceuticals, and food. The discovery of methylparaben dates back to the 1920s when researchers began investigating the antibacterial properties of parabens, leading to their development as effective preservatives. The ability of methylparaben to inhibit the growth of bacteria and fungi made it a popular choice in formulating products that require a longer shelf life.

The synthesis of methylparaben typically involves the esterification of p-hydroxybenzoic acid with methanol in the presence of an acid catalyst. This method efficiently produces methylparaben with a high degree of purity. The resulting compound appears as a white crystalline powder that is soluble in alcohol and slightly soluble in water. Its stability and effectiveness make it a preferred preservative in various formulations.

Methylparaben is widely employed in the cosmetic and personal care industry due to its antimicrobial properties. It is commonly found in products such as shampoos, lotions, and creams, where it helps prevent microbial contamination and spoilage. The low toxicity and broad-spectrum activity against bacteria and fungi contribute to its favorable reputation as a safe preservative. Additionally, its compatibility with a range of formulations enhances its utility, allowing manufacturers to incorporate it into various products without compromising quality or performance.

In pharmaceuticals, methylparaben serves as a preservative in liquid formulations, such as syrups and injections. Its use in these applications ensures the stability of active ingredients, prolonging the shelf life of medications. The compound is also recognized for its antioxidant properties, which can help protect sensitive formulations from oxidative degradation.

While methylparaben has been widely accepted in the industry, there has been increasing scrutiny regarding its safety and potential endocrine-disrupting effects. Concerns have been raised about parabens mimicking estrogen, leading to discussions about their implications for human health. As a result, some consumers and manufacturers have sought alternatives, leading to a trend toward paraben-free formulations in certain product categories. Regulatory agencies, however, have generally concluded that the use of methylparaben at concentrations typically found in consumer products is safe.

Methylparaben's role extends beyond preservation; it is also utilized in food products to prevent spoilage. Its use in food items helps maintain quality and safety by inhibiting the growth of molds and bacteria. This application further underscores its versatility and importance across various industries.

Recent research continues to explore the potential of methylparaben in novel applications and formulations. Investigations into its combination with other preservatives and natural alternatives aim to enhance its effectiveness while addressing safety concerns. As the demand for cleaner and safer formulations grows, the focus on methylparaben will likely evolve, balancing its benefits as a preservative with consumer preferences for ingredient transparency.

In conclusion, methylparaben is a crucial compound in the preservation of cosmetics, pharmaceuticals, and food products. Its antimicrobial properties, stability, and low toxicity have established it as a popular choice for preventing spoilage and extending shelf life. Ongoing research and consumer trends will shape the future of methylparaben's applications, ensuring it remains relevant in the ever-evolving landscape of product formulation.

References

2017. TLC-Densitometric and RP-HPLC Methods for Simultaneous Determination of Dexamethasone and Chlorpheniramine Maleate in the Presence of Methylparaben and Propylparaben. Journal of AOAC INTERNATIONAL, 100(2).
DOI: 10.5740/jaoacint.16-0179

2018. Estimation of the soil hazardous concentration of methylparaben using a species sensitivity approach. Environmental pollution (Barking, Essex: 1987), 242(Pt B).
DOI: 10.1016/j.envpol.2018.07.053

2019. Rapid Determination of Parabens in Water Samples by Ultra-high Performance Liquid Chromatography Coupled to Time of Flight Mass Spectrometry. Analytical sciences: the international journal of the Japan Society for Analytical Chemistry, 36(6).
DOI: 10.2116/analsci.19p409