Guaifenesin Lab report 2 PDF

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Lab report on the synthesis of Guaifenesin ...

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Abstract: includes purpose, main results, and conclusions in the past tense The purpose of this experiment was to synthesize and isolate Guaifenesin utilizing the Williamson ether synthesis method and compare the two. The results that were gathered from this synthesis and isolation were a percent yield of 387.77% and a percent recovery of 14.25% respectively. In conclusion, the experiment was successful overall, although the percent yield of synthesis of guaifenesin was very high due to error within obtaining a precipitate as the synthesis was never able to fully dry possibly due to not enough magnesium sulfate added or another possible addition error.

Introduction: Guaifenesin, a mucoactive drug, acts by loosening mucus in the airways and making coughs more productive. It is used for relief from congestion and coughing.1 In this experiment, Guaifenesin was synthesized to allow a reactant to be obtained for further comparison to guaifenesin obtained via isolation in mucus relief tablets. In order to synthesize the guaifenesin a Williamson ether SN2 synthesis reaction takes place which allows guaifenesin to form an ether. The reaction involved in the formation of an ether by Williamson ether which is a type of SN2 synthesis as an alkoxide ion allows for displacement of a halide ion from an alkyl halide and the alkoxide ion having been prepared from an alcohol reaction with a NaOH which was the strong base used. This reaction is favored by a good leaving group on the alkylating reagent and high temperature, which is why a Williams-ether synthesis was used for the synthesis of guaifenesin2.

The isolation of guaifenesin from the mucus tablets was required to observe how much was extracted. This was done so a comparison between the synthesized guaifenesin and the tablet extraction could be made. Reflux was also used within the synthesis of guaifenesin as it allows the guaifenesin to be continuously heated and cooled to as it accelerates the reaction but does not allow the reactants to leave the condenser. Liquid-liquid and solid-liquid extractions were also utilized in order to obtain a solid of the synthesized product and collect its mass, percent yield, melting point range and 1HNMR spectrum.

Experimental: First a dry and clean 25 ml round-bottomed flask and a magnetic stirrer were obtained, then .55 mL of 2-methoxyphenol and 3 mL of 95% ethanol were put into the reaction flask. The reaction flask was swirled to ensure the contents were mixed. Next, 1 mL of a 6.25M aqueous sodium hydroxide which acts as the strong base for the reaction in Williams-ether synthesis was added. The resulting solution was refluxed for ten minutes with a sand bath used as a heat source. During the ten minutes, 5 mL of 3-chloro-1,2-propanediol solution along with 5 mL of 95% ethanol were added to a clean and dried 50 mL Erlenmeyer flask. With a glass Pasteur pipette, the 3-chloro-1,2-propanediol solution was added dropwise through the refluxing reaction flask via the top of the reflux condenser. Then the resulting mixture was left to reflux for an additional one hour. For the duration of one hour, Guaifenesin was isolated from mucus relief tablets.

For the isolation to begin, two mucus relief tablets were collected, each tablet contained 400 mg of Guaifenesin, using a clean and dried mortar and pestle, the tablets were ground into a fine powder. The powder was then transferred to a dry and clean 25 mL Erlenmeyer flask and 5 mL of ethyl acetate was added, the mixture was then stirred with a glass rod for five minutes. After being stirred it was filtered via gravity filtration to a clean and dried 50 mL beaker in order to purify the tablet by removal of the fillers and binders in the tablets. Then 10mL of cold hexanes were added to the filtrate and the filtrate was placed in an ice-water bath until a white precipitate was obtained. The precipitate solid was obtained by the use of vacuum filtration and washed with 5 mL of ice-cold hexanes, the mass of the solid was found to be .114g. After the one hour reflux was completed, the reaction flask was removed from the heat source and cooled to room temperature. Then 10 mL of water was added to the flask and swirled to ensure a mix of any present solids. The contents of the flask were then added to a separatory funnel and the reaction flask was washed with 10 mL of ethyl acetate and those contents were also added to the separatory funnel. The funnel contents were then mixed and allowed to separate, the bottom aqueous layer was removed and added to the reaction flask; while the top organic layer was collected into a clean and dry Erlenmeyer flask. The aqueous layer was then added back into the separatory funnel and the extraction process with ethyl acetate was repeated twice more. Next, magnesium sulfate was added to the previously collected organic layer in order to remove any residual water. Then, the mixture was filtered via gravity filtration and the resulting filtrate was placed in a 100 mL round-bottom flask to have the solvent removed by the use of rotary evaporation. Once all the solvent was removed, 10 mL of ice-cold hexanes and a magnetic stir bar were added and rapidly stirred until a white precipitate was supposed to be formed, however a

white precipitate never formed for this experiment, instead the solvent remained in a liquid state. Nonetheless, a mass was able to be found by calculating the mass of the empty 100 mL round bottom flask from previous experiments and then taking the weights of an empty 100 mL beaker and the beaker with the solution in it. Finally, ending with a mass of 3.49g for the synthesized guaifenesin. The 1H NMR was run for both synthesis and isolation of guaifenesin. The results were:

1

H NMR (CDCL3) 2.58 ppm (t, 1H), 3.30 (d, 1H), 3.75-3.90 (m, 5H), 4.03-4.20 (m, 3H),

6.86-7.05 (m, 4H). For the isolation, the 1H NMR (CDCL3) 2.79ppm (s ,1H), 3.86 ppm (d ,5H) , 4.10 ppm ( s, 3H), 6.93 ppm (m, 4H).

Results: Compound:

Mw (g/mol)

Amount used:

Moles Used (g)

Density (g/mL)

0.0045513

1.1287

(mL) 2-methoxyphenol

124.14

.55

Sodium hydroxide

39.997

1

X

3-chloro-1,2-propane 110.54

.5

0.00597

X 1.32

diol 95% ethanol

X

3.5

X

.7893

Ethyl acetate

X

35

X

.90

Hexanes

X

30

X

.6606

Water

X

10

X

1

Table 1: Reagent and solvent table Percent yield for synthesis of Guaifenesin:

387.77%

Percent recovery for isolation of Guaifenesin:

14.25%

Table 2: Percent recovery and yield for synthesis and isolation of Guaifenesin. Trials:

Melting point ranges for synthesis of guaifenesin (Co)

1.

72-82

2.

77-81

3.

78-83 Table 3: Synthesis of Guaifenesin melting point range

Trials:

Melting point ranges for isolation of guaifenesin (Co)

1.

78-80

2.

77-81

3.

78-83 Table 4: Isolation of Guaifenesin melting point range

The percent yield for the synthesis was calculated by taking the ending mass of the synthesis which was 3.49 grams and dividing it by the theoretical yield of .90 g of guaifenesin. Then that value was multiplied by 100 to make a percentage. The value is very high possibly due to the fact that the synthesized guaifenesin did not dry out all the way and the mass calculated is due to leftover compounds and such that prevented the precipitate from forming. The percent recovery for the isolated guaifenesin is 14.25% this was found by taking the overall mass of the precipitate solid of the tablets and dividing it over .800 as that was the theoretical yield of guaifenesin, then multiplying that value by 100 to once again form a percentage.

Discussion: What the results from this experiment show is that the synthesis of guaifenesin and the isolation from the mucus tablets was somewhat successful, somewhat in the fact that the synthesis of guaifenesin did not precipitate and remained in a liquid state. This only affected the percent yield and not the overall compound synthesis of guaifenesin, as an 1H NMR was performed on the liquid synthesis and it showed very similar results to the 1H NMR in the appendix. The liquid synthesis not becoming a solid could have been caused by not adding enough magnesium sulfate to allow total drying of the synthesis, an issue could have arisen with the stirring and addition of hexanes as well that could cause the precipitate not to form. In conclusion, the overall experiment, especially the percent yield could have been improved on by the formation of a precipitate.

Conclusion- Overall, the experiment was successful, although the synthesis did not end up as a solid precipitate like planned, the mass when taken as well as the H1 NMR performed on the

liquid synthesized product was still at a similar chemical shift and signals as a synthesized guaifenesin would produce. Furthermore, the percent yield and recovery for the synthesis and isolation were 387.77% and 14.25% respectively. So, overall, yes the experiment was successful.

References: Wang, Z. (2010). Williamson Ether Synthesis. In Comprehensive Organic Name Reactions and Reagents, Z. Wang (Ed.). https://doi.org/10.1002/9780470638859.conrr673

Albrecht, H.H., Dicpinigaitis, P.V. & Guenin, E.P. Role of guaifenesin in the management of chronic bronchitis and upper respiratory tract infections. Multidiscip Respir Med 12, 31 (2017). https://doi.org/10.1186/s40248-017-0113-4

Ryan G. Stabile and Andrew P. Dicks Journal of Chemical Education 2003 80 (3), 313 DOI: 10.1021/ed080p313

Appendix: include 1HNMR spectrum...