Guaifenesin Chemical Properties

Melting point:

77-81 °C

Boiling point:

215 °C (19 mmHg)

Density 

1.1825 (rough estimate)

refractive index 

1.5550 (estimate)

Flash point:

215°C/19mm

storage temp. 

2-8°C

solubility 

50g/l (experimental)

pka

13.53±0.20(Predicted)

form 

Solid

color 

White to Off-White

Water Solubility 

5 g/100 mL (25 ºC)

Merck 

14,4555

BRN 

2049375

InChIKey

HSRJKNPTNIJEKV-UHFFFAOYSA-N

LogP

1.390

CAS DataBase Reference

93-14-1(CAS DataBase Reference)

NIST Chemistry Reference

3-(O-methoxyphenoxy)-1,2-propanediol(93-14-1)

EPA Substance Registry System

Guaifenesin (93-14-1)

Safety Information

Hazard Codes 

Xn

Risk Statements 

22-36/37/38

Safety Statements 

26-36

WGK Germany 

1

RTECS 

TY8400000

Hazard Note 

Harmful

TSCA 

Yes

HS Code 

29093090

Hazardous Substances Data

93-14-1(Hazardous Substances Data)

Toxicity

LD50 oral in rabbit: 2553mg/kg

MSDS

• Language:English Provider:ACROS
• Language:English Provider:SigmaAldrich
• Language:English Provider:ALFA

Guaifenesin Usage And Synthesis

Description

Guaifenesin is an oral expectorant drug. The expectorant action of guaifenesin is mediated by stimulation of the gastrointestinal tract. It is a common ingredient in prescription and over-the-counter medications used to treat cough due to colds and minor upper respiratory infections. Additionally, Guaifenesin is also a centrally-acting muscle relaxant and is used routinely in combination with analgesics and sedatives in large-animal veterinary surgery.

Chemical Properties

This substance is a white crystalline powder with a melting point of 78.5-79°C and a boiling point of 215°C (2.53kPa). It is soluble in 20ml of water and ethanol, chloroform, glycerin, and dimethylformamide. It is easily soluble in benzene but insoluble in petroleum ether. It has a slightly bitter taste and a slightly particular odor.

Originator

GG Cen,Central,US,1975

History

Guaifenesin was originally derived from the guaiac tree and used by Native Americans for health purposes. Synthesis of guaifenesin was first reported in 1912. Guaifenesin has been used in the treatment of respiratory diseases since the nineteenth century. The United States’ Food and Drug Administration (FDA) approved guaifenesin for use in overthe- counter medications in 1989. Guaifenesin is widely consumed alone and combined with antihistamines, cough suppressants, and decongestants. Guaifenesin is also a centrally acting muscle relaxant and is used routinely in combination with analgesics and sedatives in large-animal veterinary surgery.

Uses

Guaifenesin is a muscle relaxant with expectorant properties often used as an expectorant to facilitate the removal of phlegm from the airways in acute respiratory tract infections. Guaifenesin comes in tablet and capsule form, as syrup, as dissolving granules, and recently as an extended-release (longacting) tablet. The tablets, capsules, dissolving granules, and syrup are usually taken with or without food every 4 h as needed. The extended-release tablet is usually taken with or without food every 12 h.

Definition

ChEBI: Guaifenesin is a member of methoxybenzenes.

Manufacturing Process

A mixture of o-methoxyphenol (57 g), glycidol (32 g) and pyridine (1 g) is warmed to 95°C at which temperature a vigorous reaction takes place. The reaction mixture is cooled to prevent the temperature rising above 110°C. When the exothermic reaction has subsided the reactants are heated at 95°C for one hour longer and then distilled under low pressure. The main fraction boils in the range 176°C to 180°C/0.5 mm. It crystallizes on cooling. Recrystallization from benzene gives the pure product, MP 78.5°C to 79.0°C.

brand name

Mucinex (Adams).

General Description

Guaifenesin is an expectorant, widely used in the treatment of cough. Its mode of action involves the alleviating of cough discomfort by increasing sputum volume and decreasing its viscosity, thus resulting in effective cough.
Pharmaceutical secondary standards for application in quality control, provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to the preparation of in-house working standards.

Mechanism of action

Guaiphenesin facilitates secretion from bronchial mucous membranes, thus relieving a cough in colds, bronchitis, and bronchial asthma.

Synthesis

Guaiphenesin, 3-(o-methoxyphenoxy)-1,2-propandiol (23.2.3), is synthesized by reacting guiacol with 3-chloropropan-1,2-diol or with glycidol.

Veterinary Drugs and Treatments

In veterinary medicine, guaifenesin is used to induce muscle relaxation and restraint as an adjunct to anesthesia for short procedures (30 – 60 minutes) in large and small animal species. There are combination oral products containing guaifenesin for treating respiratory conditions in horses.
In human medicine, guaifenesin has long been touted as an oral expectorant, but definitive proof of its efficacy is lacking.

Environmental Fate

Guaifenesin’s production and use as veterinary and human medicines may result in its release to the environment through various waste streams.
If released to air, an estimated vapor pressure of 1.5× 10–6 mm Hg at 25 ℃ indicates that guaifenesin will exist in both the vapor and particulate phase.
Based upon an estimated Henry’s law constant of 4.4 × 10^-11 atm-m³ mol^-1, volatilization from moist soil surfaces or from water surfaces are not expected to be important fate processes for guaifenesin.
Guaifenesin is expected to have high mobility in soil based upon an organic carbon–water partition coefficient (Koc) of 140, which indicates that it will have more solubility in water and is less likely to adsorb onto organic matter in soil and plants.

Toxicity evaluation

Guaifenesin is an adrenergic antagonist in a class of medications called expectorants. It stimulates afferent receptors in the gastric mucosa, reflexively increasing glandular secretion by the respiratory epithelium promoting lower respiratory tract drainage by thinning bronchial secretions, lubricating irritated respiratory tract membranes through increased mucous flow, and facilitating removal of viscous mucus. The onset of action appears to be within 15–30 min. Guaifenesin is believed to alleviate cough discomfort by improving sinus and bronchial drainage, increasing sputum volume, and decreasing sputum viscosity, thereby promoting effective cough. In one study, the effect of guaifenesin to increase mucociliary clearance from the lung was greater in patients with chronic bronchitis than in healthy subjects.
In another study, guaifenesin inhibited the cough reflex sensitivity in subjects with an upper respiratory tract infection (cough receptors are transiently hypersensitive), but not in healthy volunteers. Possible mechanisms include a central antitussive effect or a peripheral effect by increased sputum volume serving as a physical barrier, shielding cough receptors within the respiratory epithelium.
As a centrally acting muscle relaxant, guaifenesin is believed to depress or block nerve impulse transmission at the internuncial neuron level of the subcortical areas of the brain, brain stem, and spinal cord. It also has mild analgesic and sedative actions.

References

[1] Peter V. Dicpinigaitis and Yvonne E. Gayle, Effect of Guaifenesin on Cough Reflex Sensitivity, 2003, vol. 124, 2178-2181 DOI:10.1378/CHEST.124.6.2178
[2] Leonid Kagan, Eran Lavy and Ammon Hoffmann, Effect of mode of administration on guaifenesin pharmacokinetics and expectorant action in the rat model, Pulmonary Pharmacology & Therapeutics, 2009, vol. 22, 260-265 DOI:10.1016/j.pupt.2008.12.020
[3] Sittig's Pharmaceutical Manufacturing Encyclopedia
[4] Synthesis of Essential Drugs (2006, Elsevier)
[5] Plumb's Veterinary Drug Handbook
[6] https://pubchem.ncbi.nlm.nih.gov/compound/Guaifenesin

Guaifenesin(93-14-1)Related Product Information

• Guaiacol
• 3-Methoxyacetophenone
• 1,2,3-PROPANETRIOL GLYCIDYL ETHER
• DIGLYCEROL
• 2-(Trifluoromethoxy)aniline
• Potassium guaiacolsulfonate hemihydrate
• GLYCERYL MONORICINOLEATE
• Glycerol
• Anisole
• Ethylbenzene
• 4'-Methoxyacetophenone
• 4-Methoxybenzoic acid
• p-Anisaldehyde
• C8E3
• DIGLYCIDYL ETHER
• 3-(METHOXYMETHOXY)BENZALDEHYDE
• (Trifluoromethoxy)benzene
• Ethylene glycol diglycidyl ether