Pharmaceutical research labs perform chemical reactions between organic molecules that contain mostly carbon. Since the atoms in organic molecules tend to be nonmetals, then the bonds that hold them together are covalent bonds. Only a few elements on the periodic table are nonmetals: C, N, O, S, Cl, and F. This small number of elements can be bonded together in different quantities, bonding types (single, double, triple bonds), and structural patterns to form over 10 million known molecules! The billions of dollars generated by the pharmaceutical industry is a prime example of how important organic chemistry is to our healthcare industry.
In this lab, you will perform an organic synthesis to make aspirin. Aspirin is the trade name for the molecule acetylsalcylic acid. The earliest known use of this molecule has been traced back to fifth century B. C. The Greek physician Hippocrates described an extract of willow tree bark, a bitter powder that could be used to reduce fevers. In 1829, salicin was isolated from willow bark and used as a pain reliever. Unfortunately, salicin was not very popular, since it was found to be very acidic and a stomach irritant.
In 1897, a German chemist named Felix Hoffman was working for the Bayer chemical company. Hoffman was looking for a less acidic pain reliever that his father could take for his arthritis. His research led to the synthesis of acetylsalicylic acid or aspirin. Bayer patented the name and marketed the product in 1899. It was a huge success and sales grew rapidly. In fact, the company set up by Friedrich Bayer & Company is generally reckoned to have been the first pharmaceutical company, and the production of aspirin is generally accepted to have laid the foundation of the modern pharmaceutical industry.
Interestingly enough it wasn’t until the 1970’s that scientists began to understand how aspirin actually worked as a pain reliever. Today 80 billion aspirin tablets are consumed every year across the globe to reduce fevers, relieve pain, and even help prevent heart attacks. In commercial aspirin products, a small amount of aspirin (300 to 400 mg) is bound together with a starch binder and sometimes caffeine and buffers to make an aspirin tablet. The basic conditions in the small intestine break down the aspirin to yield salicylic acid, which is absorbed into the bloodstream.
The addition of a buffer reduces the irritation caused by the carboxylic acid group of the aspirin molecule. Aspirin can be produced in a one-step chemical process by reacting salicylic acid with acetyl chloride, according to the reaction: http://www. earlham. edu/~chem/chem111f03/labs/Experiment%2011. pdf Name Period Date Aspirin is a white solid that is almost completely insoluble in water. We will use this physical property of our product to separate it from the final solution. If time allows, we will synthesize methyl salicylate, which is another ester of salicylic acid.
It occurs in a wide range of plants and is known as ‘oil of wintergreen’. It is still used in candies and in ointments for joint and muscle pains. Thin layer chromatography (TLC) is used to separate and identify aspirin. Small amounts of the synthesized product, starting material (salicylic acid) and commercial aspirin are placed along one edge of a chromatography plate. The plate is then placed in a container with solvent. With the plate acting like a wick, the solvent flows up the chromatogram, carrying samples with it.
Molecules that are more soluble in the solvent will move higher on the paper; the molecules that are more attracted to the plate will remain closer to the original line. After removing the plate, the samples can be detected with UV light. Safety Notes 1. The acetyl chloride and pyridine should only be dispensed in a fume hood. 2. Always wear appropriate eye protection and gloves while handling the chemicals. Materials Gloves goggles suction filtration test tube ice bath rubber tubing 150mg salicylic acid 0. 1 mL acetyle chloride 5mL cold water 0. 1mL pyridine timer rubber stopper.
Procedure Part A- Preparation of Aspirin (adapted from Journal of Chemical Education • Vol. 75 No. 6 June 1998 • “An Efficient Microscale Procedure for the Synthesis of Aspirin”, Sangeeta Pandita and Samta Goyal) 1. Put on gloves and avoid getting reagents on your skin! Place 150 mg (0. 001 mol) of salicylic acid in a 10 mL test tube and add 0. 1 mL of pyridine or equivalent solvent (just sufficient to dissolve it) while the tube rests in an ice bath. Keep the test tube in the fume hood! 2. Point the open end of the test tube away from you and your partners.
Occasionally the reaction goes quickly and shoots material out of the tube! Add 0. 1 mL of acetyl chloride to the tube. Keep the mixture in the fume hood! 3. The mixture becomes viscous at this stage. Place tube in the ice bath for 15 min. – it does not need to be in the hood. http://www. earlham. edu/~chem/chem111f03/labs/Experiment%2011. pdf Name Period Date 4. While waiting, set up a vacuum filter flask with a Buchner funnel and a piece of filter paper which just fits the bottom of the funnel, as shown in Figure 2 below. Attach a thick rubber tube to an aspirator mounted on a water faucet.
5. Add 5 mL of cold water to the test tube and cap it with a rubber stopper. Shake the mixture. Do this cautiously at first until you are sure that no violent reaction is occurring. The mixture should turn cloudy. Shaking is continued until a white product appears (it may take several minutes, be patient! ) 6. Turn on the water faucet all the way and check to be sure you have good suction. Break the suction by disconnecting the tube from the flask (leave the water running). Pour the mixture into the funnel, trying to get as much of the solid transferred as possible.
Connect the hose and apply full suction for at least 30 seconds. Wash the crystals with cold water. Break the suction. Do not just turn off the water; this may create a back-flow of the water into your filter flask. Dry them on the filter paper for about 5 min. Part B- Recrystallization 1. Carefully scrape off most of your crystals into a 50 mL beaker. SAVE THE FILTER PAPER! Add about 3 mL of cold water and place the mixture on a hot plate in a hood. Heat until all of the crystals dissolve. When the crystals are completely dissolved, remove the beaker and allow it to cool.
You should see nice crystals of aspirin beginning to form! When the recrystallization is complete, filter again, and dry. SAVE THE FILTER PAPER for the next step! Part C- Oil of Wintergreen 1. Place 1. 00 gram of salicylic acid in a test tube. (record the actual mass used) 2. Add 5 ml of methyl alcohol and 3 drops of concentrated sulfuric acid. 3. Heat this mixture in a boiling water bath for 15 min. 4. Note the odor of the liquid in your tube, remember to WAFT. http://www. earlham. edu/~chem/chem111f03/labs/Experiment%2011. pdf Name Directions: Use the space at the right to answer the questions on the left.
Period Date Question 1. Calculate the theoretic yield of aspirin in grams. Answer 2. Use your answer in #1 to calculate % yield of your product. 3. When aspirin was first produced, it irritated the stomach. What component was added to make it gentler? 4. Draw the complete Lewis dot structure of aspirin (include the lone pairs). 5. Methyl salicylate (wintergreen oil) is an irritant that not only relieves aches and pains but also stimulates blood flow. What do you experience when eating a wintergreen lifesaver? And how does your experience explain the effects wintergreen oil has on your sore muscles?
6. The LD50 of aspirin is 1. 5 g/kg/day. Calculate the lethal dosage for a 10 kg (22 lb) child. 7. Extra strength aspirin tablets contain 500 mg of aspirin. How many tablets would be a lethal dose? 8. Identify the type of reaction that occurred when salicylic acid reacted with acetyl chloride. 9. Identify the type of reaction that occurred when salicylic acid reacted with methanol.
10. What mass of salicylic acid is needed to produce one extra strength tablet (500 mg aspirin) if the reaction has a 60% yield? http://www. earlham. edu/~chem/chem111f03/labs/Experiment%2011. pdf.