lab report

SYNTHESIS OF ASPIRIN

OBJECTIVES: To synthesize aspirin, a common pain killer, in a two-step synthesis. To perform saponification and esterification. To characterize the final product by IR and NMR

TIME ALLOCATED: TWO LAB PERIOD

Background

Aspirin, also known as acetylsalicylic acid, is an over the counter (OTC) medication used to treat inflammation and pain. It is synthesized in a two-step synthesis: 1) saponification and 2) esterification.

Saponification

The word “saponification” comes from the Latin word “sapo” meaning “soap”. This is perhaps the oldest documented organic reaction, dating back to about 2500 B.C. in ancient Babylon where there are records of using water, alkali and cassia oil to make a soap-like substance. Later, the ancient Romans reported the use of tallow (rendered animal fat) to make soap. The animal fat (tri-ester of glycerol, or triglyceride) reacts with lye (NaOH) to give the carboxylate salts of the fatty acids.

Acetylation (esterification): It is the reaction that introduces an acetyl functional group into a chemical compound. A common reagent utilized in acetylation reaction is acetic anhydride.

Reaction Scheme

Experimental

Step 1. First week

1. Add 0.50 mL methyl salicylate to a large test tube.

2. Add 4.0ml of 6M NaOH, (*add boiling stick) and heat to a gentle boil for about 30 min.

3. Remove boiling stick and cool the tube to room temperature

4. Add 5.0 mL of 8M sulfuric acid. A precipitate should form.

5. Cool in an ice bath and collect the precipitate on a Buckner Funnel, washing with cold water.

6. Recrystallize in another large test tube containing about 10 mL of water. (*add boiling stick-boil to dissolve-remove boiling stick-scrape the side of test tube with glass stirring rod-then cool and allow crystals to form)

7. Collect crystals on Buchner funnel.

8. Weigh your crude salicylic acid, take the melting point, and take an IR. YOUR PRODUCT WILL BE USED FOR THE SECOND STEP.

Step 2. Second week

1. Weigh your salicylic acid into a small round- bottom flask, and add 3.0 equivalents of acetic anhydride (d=1.08 g/mL) AND a stir bar, start stirring.

2. Add one drop of phosphoric acid and heat (while stirring) on a water bath to 85˚ to 90˚ for about 20 minutes.

3. Remove from heat, add 2 mL of water, cool and add another 2 mL of water. Continue to cool, crystals should form.

4. Collect the precipitate, washing with cold water on a Buckner Funnel.

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5. Recrystallize from water.

6. Collect IR, and NMR spectra of the product as well as a melting point.

Real-life example

Kastrati et al. from University of Illinois synthesized and studied the properties of an aspirin pro-drug for cancer treatment. They designed a strategy where they added an anti-inflammatory drug to standard cancer regiments to improve patient outcome. One such drug, aspirin (acetylsalicylic acid, ASA), had been explored for cancer chemoprevention and anti-tumor activity. Because prolonged ASA use may cause gastrointestinal toxicity, a prodrug strategy was implemented successfully. In this prodrug design the carboxylic acid of ASA is masked and additional pharmacophores were incorporated.

Post -lab assignment

FULL LAB REPORT

For this two-week experiment you will write a full lab report, that will be a little bit more comprehensive than the weekly one you have done so far. Here some points to consider:

- Abstract: this section is still very concise and it has it summarize your results and the type of reactions done. Make sure you include: yield for both steps and any results you obtained

- Introduction: for the full report the introduction has o be more detailed. Include background information about the type of reactions you conducted during both weeks with TWO external references for each. State why the reactions are important, supporting your statement with scientific references. Include TWO applications with their references.

- Discussion: 1) table of reagents with structures and appropriate properties (mp, bp, MW, d etc.). 2) mechanism for both steps. 3) calculations for yield SHOWING the actual calculations. 4) Discuss the procedure, the NMR, mp and IR. Explain how the data confirm the presence (or absence) of your desired product.

- Experimental: use the format for experimental section for both steps (from first week and second week). Include NMR assignment when applicable, with J coupling, ppm and multiplicity (singlet, doublet etc) Do not forget to assign the peaks to specific proton in the molecule.

- Conclusions: brief statement about your results

References

1. Kastrati, I., Delgado-Rivera, L., Georgieva, G., Thatcher, G.R., Frasor, J. Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells. J. Vis. Exp. (119), e54798, doi:10.3791/54798 (2017).