Guaifenesin
[CAS# 93-14-1]

Identification

• Classification: API >> Respiratory medication >> Expectorant
• Name: Guaifenesin
• Synonyms: 3-(2-Methoxyphenoxy)-1,2-propanediol; Guaiacol glyceryl ether; Glycerol guaiacolate
• Molecular Formula: C₁₀H₁₄O₄
• Molecular Weight: 198.22
• CAS Registry Number: 93-14-1
• EC Number: 202-222-5
• SMILES: COC1=CC=CC=C1OCC(CO)O

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*
• Melting point: 80 - 82 °C (Expl.)
• Boiling point: 356.8±27.0 °C 760 mmHg (Calc.)^*, 380.5 °C (Expl.)
• Flash point: 169.6±23.7 °C (Calc.)^*
• Solubility: DMSO: 40 mg/mL, Water: 25 mg/mL (Expl.)
• Index of refraction: 1.538 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302
• Safety Statements: P264-P270-P301+P317-P330-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335
Reproductive toxicity	Repr.	2	H361

Discovery and Applications

Guaifenesin, chemically known as 3-(2-methoxyphenoxy)propane-1,2-diol, is an expectorant commonly used in the treatment of respiratory conditions associated with mucus congestion. It has the molecular formula C₁₀H₁₄O₄ and is characterized by a glycerol backbone ether-linked to a methoxy-substituted phenyl group.

The compound was first synthesized and introduced in the mid-20th century as a therapeutic agent to facilitate the clearance of mucus from the airways. Guaifenesin acts by increasing the volume and reducing the viscosity of bronchial secretions, thereby promoting expectoration and improving airway clearance. This pharmacological effect makes it a staple ingredient in many over-the-counter cold, cough, and flu remedies.

Guaifenesin’s mechanism of action involves stimulating the respiratory tract’s mucus-producing glands to secrete a more fluid mucus. This alteration in mucus consistency eases its removal by ciliary action and coughing. The drug is typically administered orally in the form of tablets, syrups, or capsules, with dosing adjusted based on patient age and clinical indication.

Beyond its use as an expectorant, guaifenesin has been investigated for potential benefits in conditions involving chronic respiratory tract diseases, including chronic bronchitis and asthma, where mucus clearance is impaired. It is generally well tolerated, with adverse effects being rare and mild, commonly limited to gastrointestinal discomfort or allergic reactions.

Pharmacokinetically, guaifenesin is rapidly absorbed following oral administration, metabolized in the liver, and excreted primarily via the kidneys. Its half-life supports dosing intervals commonly every four to six hours. The drug does not exhibit significant interactions with other medications, making it safe for use in combination therapies.

In pharmaceutical synthesis, guaifenesin is produced by etherification reactions involving glycerol derivatives and substituted phenols under controlled conditions. This synthetic accessibility has allowed widespread production and formulation.

In summary, guaifenesin is a widely used expectorant that aids mucus clearance in respiratory conditions. Its chemical structure and pharmacological effects underpin its role in symptomatic relief of mucus-related airway congestion.

References

1970. Pharmacokinetics and Metabolism of Glyceryl Guaiacolate in Ponies. American Journal of Veterinary Research, 31(3).
DOI: 10.2460/ajvr.1970.31.03.469

2020. A new molecularly imprinted polymer for selective extraction and pre-concentration of guaifenesin in different samples: Adsorption studies and kinetic modeling. Journal of Separation Science, 43(6).
DOI: 10.1002/jssc.201900940

2021. High-Performance Liquid Chromatography Method for Simultaneous Determination of Guaifenesin, Salbutamol Sulfate and Guaifenesin Impurity (Guaiacol). Journal of Chromatographic Science, 59(8).
DOI: 10.1093/chromsci/bmaa128