Guaifenesin

Topics: Ether, Alcohol, Alkyl Pages: 8 (1424 words) Published: April 19, 2015


Synthesis and Isolation of Expectorant Guaifenesin

By: Ben DuBose
Dr. Cossey
3361L

Abstract

The purpose of this experiment was to isolate and synthesize Guaifenesin. Isolation was performed with the use of two Guai-Aid Tablets, each of which contained 400mg of pure Guaifenesin. Reflux, a technique used to heat a mixture without evaporating the solution, was used to synthesize Guaifenesin through a Williamson Ether Synthesis reaction with an SN2 mechanism. Introduction

In this two-week experiment, guaifenesin, an expectorant found in over-the-counter cough syrups and tablets, was prepared through the Williamson Ether Synthesis model. The model involved an SN2 mechanism between the sodium phenoxide salt derived from guaiacol (2-methoxyphenol) and 3-chloro-1,2-propanediol (Wildman, 2003). With the Williamson Ether Synthesis specializing in producing ethers, it was ideal for this lab because of the alcohol and the alkyl halide used.  After the synthesis and isolation of Gauifenesin was completed, the melting point ranges were observed and percentage yields were calculated to compare with the values of authentic guaifenesin and guaiacol.  Reflux was used to synthesize Guaifenesin. Guaifenesin is an expectorant, meaning it helps loosen congestion in one’s chest and throat, making it easier to cough. Guaifenesin is used to reduce chest congestion caused by the common cold, infections, or allergies. It allowed ciliary movement to carry the loosened secretions, which prevent build up in the respiratory tract (London, 2014). Throat aid is not the only use, however Guaifenesin has also been promoted to facilitate conception right before ovulation by thinning and increasing the cervical mucus (Early-Pregnancy-Tests.com).

Procedure
550 ul guaiacol was dissolved in 3 mL of 95% ethanol and then 1 mL of 6.25 M aqueous NaOH was added to the solution and refluxed. 500 ul 3-chloro-1,2-propanediol was dissolved into 0.5 mL 95% ethanol. The alkyl halide solution was added drop wise through the top of the reflux condenser and the reflux process was continued for an hour. After the hour of reflux, the aqueous solution was extracted in a separatory funnel and rinsed out by ethyl acetate. The organic layer was collected and dried with magnesium sulfate. The solution was placed in an ice bath and then underwent vacuum filtration. The solution was left overnight and crystals were formed once the solution evaporated to create synthesized Guaifenesin. For the isolation process, a Guai-Aid tablet was crushed into a powder and added to 5 mL ethyl acetate and then underwent gravity filtration to rid of the insoluble material. 10 mL hexanes were added to the solution and were then placed in an ice bath so crystals would form. Results

Gauifenesin was synthesized after the conjugate base, 2-methoxythenol, was formed by the reaction of 2-methoxypehnol and NaOH. The conjugate base then underwent an SN2 reaction involving 3-chloro-1,2-propanediol to form pure Gauifenesin (Figure 1). Figure 1

After the procedure was completed and both the synthesis and isolation of Guaifenesin was complete, the melting point and NMR spectra (Figure 2) of both substances were taken to compare to the theoretical values. After conducting three trials for the melting point values, the average melting point range for the synthesis of Guaifenesin was 66.3C – 68.7C (Table 1) and the average melting point range for the isolation of Guaifenesin was 73.3C – 75.3C (Table 2). Synthesis of Guaifenesin

Trial
Melting Point Range

1
66°C - 69°C

2
65°C - 66°C

3
68°C - 71°C
Average

66.3°C - 68.7°C
Table 1

Isolation of Guaifenesin

Trial
Melting Point Range

1
72°C - 74°C

2
73°C - 75°C

3
75°C - 77°C
Average

73.3°C - 75.3°C
Table 2
Also calculated were the percentage yields of both the isolated...

References: 1.) Wildman, R., & Coleman, W. (2003, March 1). Featured Molecules: Enantiomers of Guaifenesin. Retrieved November 13, 2014, from http://pubs.acs.org/doi/abs/10.1021/ed080p315
2.) London, M. (2014, June 16). The Truths and Myths of the use of Guaifenesin for Fibromyalgia. Retrieved November 13, 2014, from http://web.mit.edu/london/www/guai.html
3.) Guaifenesin, FertileCM, and Cervical Mucus. (n.d.). Retrieved November 22, 2014, from http://www.early-pregnancy-tests.com/guaifenesin.html
4.) Iverson. (n.d.). SN2 Reaction. Retrieved November 22, 2014, from http://iverson.cm.utexas.edu/courses/310N/ReactMoviesFl05 /SN2text.html
5.) James. (2014, January 1). The Williamson Ether Synthesis. Retrieved November 22, 2014, from http://www.masterorganicchemistry.com/2014/10/24/the- williamson-ether-synthesis/
6.) McConathy, J., & Owens, M. (2003, April 25). Stereochemistry in Drug Action. Retrieved November 22, 2014, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC353039/
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