TITLE: MAKING ASPIRIN.
AIM: My aim in this experiment is to know the different methods used in making aspirin, the most suitable methods in making it, the apparatus needed in making the aspirin, the procedures and methods used in making aspirin.
After this, I will be performing an experiment in the laboratory on making aspirin, using the most suitable method and I will also be looking at the evaluation.
BACKGROUND INFORMATION.
HISTORY OF ASPIRIN.
Aspirin (acetylsalicylic acid) is a simple molecule first synthesized in Germany 150 years ago. Its pain-relieving properties were recognized and exploited commercially 100 years ago. In the last 50 years, aspirin has been shown to have remarkable antithrombotic benefits.
Aspirin's antithrombotic effect is mediated by inhibition of blood platelets. The drug blocks a platelet enzyme, cyclo-oxygenase, by acetylating the enzyme's active site. Inhibition of the enzyme blocks production of an important prothrombotic agent known as thromboxane A2. Thromboxane A2 causes activation and aggregation of platelets, which is an early step in thrombosis. Aspirin is more effective in preventing arterial thrombosis (myocardial infarction, stroke) than venous thrombosis (deep venous thrombosis, pulmonary embolism). The explanation for this difference seems to be that platelets play a larger role in causing arterial thrombosis.
Aspirin is a member of a family of chemicals called salicylates. These chemicals have been known to people interested in medicine for centuries.
One of the first and most influential physicians, Hippocrates, wrote about a bitter powder extracted from willow bark that could ease aches and pains and reduce fevers as long ago as the fifth century B.C. In the 1700s, the scientist Reverend Edmund Stone wrote about the success of the bark and the willow in the cure of the "agues," or fevers with aches. With a bit of chemical detective work, scientists found out that the part of willow bark that was (1) bitter and (2) good for fever and pain is a chemical known as salicin.
This chemical can be converted (changed) by the body after it is eaten to another chemical, salicylic acid (a compound that can be obtained from many plants including willow, birch, and myrtle trees. It was once used as a painkiller, but because it causes severe stomach pain it has been replaced by aspirin. But salicylic acid doesn't hurt if applied to the skin, and it is used today in wart-removing medicines). It was a pharmacist known as Leroux who showed in 1829 that salicin is this active willow ingredient, and for many years it, salicylic acid (made from salicin for the first time by Italian chemist Piria), and close relatives were used at high doses to treat pain and swelling in diseases like arthritis and to treat fever in illnesses like influenza (flu).
Unfortunately, Hoffmann had to wait for fame. He finished his initial studies in 1897, and his employers didn't pay much attention to it because it was new and they were cautious - they didn't think it had been tested enough. By 1899, though, one of Bayer's top chemists, a scientist named Dreser, had finished demonstrating the usefulness of the potent new medicine and even gave it a new name: aspirin. It is believed that the name comes from a plant relative of a rose that makes salicylic acid (several plants make this compound, not just the willow). The Bayer Company could then support the tested medicine; they spread the word and marketed the new pill widely.
Over the next hundred years, this medicine would fall in and out of favor, at least two new families of medicines would be derived from it, and innumerable research articles would be published about aspirin. Thousands have been published in the past five years alone! One of the most important pieces of research about aspirin came in the early 1970s, when a British scientist named John Vane and his colleagues showed how aspirin works (see the following sections). His work was so important that he and his colleagues were awarded the Nobel Prize in Medicine in 1982. Dr. ...
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Over the next hundred years, this medicine would fall in and out of favor, at least two new families of medicines would be derived from it, and innumerable research articles would be published about aspirin. Thousands have been published in the past five years alone! One of the most important pieces of research about aspirin came in the early 1970s, when a British scientist named John Vane and his colleagues showed how aspirin works (see the following sections). His work was so important that he and his colleagues were awarded the Nobel Prize in Medicine in 1982. Dr. Vane was even made a British knight for his work!
Today, more potent platelet inhibitors than aspirin are available, but aspirin remains the most commonly used drug in this category and is still our most cost-effective antithrombotic drug. Aspirin (either 81 mg or 325 mg daily) is indicated in the following conditions:
* Unstable angina (acute coronary syndrome).
* Acute myocardial infarction.
* Secondary prevention of myocardial infarction
* Secondary prevention of stroke (carotid or primary cerebrovascular disease).
* Prevention of peripheral arterial thrombosis.
Aspirin, also known as acetylsalicylic acid, has numerous pharmaceutical applications. First synthesized in 1897, aspirin is only found experimentally in one crystal structure. There were claims of additional forms in the late 1960s and early 1970s. However, those studies were not supported by sufficient physical data to prove the existence of these forms. Based on this history and the importance of this molecule, researchers studied its potential for polymorphs using Accelrys' C2.Polymorph, commonly known as the Polymorph Predictor.
C2.Polymorph was successful in predicting the known crystal structure of aspirin, which contains a nonplanar conformer. Additional low-energy structures were also predicted that contained a planar conformer. While semiempirical and ab initio calculations indicated that the planar conformation is less stable than the nonplanar conformation, force field calculations suggested that the planar conformation is more stable.
The researchers proposed that additional polymorphs of aspirin might be found if experimental crystallization conditions could be developed that would stabilize the planar conformation. Such ideas will help researchers in their attempts to find additional experimental forms of aspirin (Reference: Payne, R.C. Rowe, R.J. Roberts, M.H. Charlton, R. Docherty, J. Comp. Chem., 1999, 20, 262-273).
CHEMICAL MOLECULAR STRUCTURE OF ASPIRIN.
Aspirin, one of the first drugs to come into common usage, is still mostly the widely used in the world - approximately 35,000 metric tonnes are produced and consumed annually, enough to make over 100 billion standard aspirin tablets every year. Aspirin, also known as 'acetylsalicylic acid', has a chemical formula of C9H8O4.
Aspirin is analgesic, anti-inflammatory, antipyretic and is an inhibitor of platelet aggregation. It inhibits fatty acid cyclo-oxygenase by acetylation of the active site of enzyme and the pharmacological effects of aspirin are due to the inhibition of the formation of cyclo-oxygenase products including prostaglandins, thromboxanes and prostacyclin.
The chemical structure of aspirin.
Molecular Production Structure of aspirin.
ASPIRIN PRODUCTION.
Aspirin is analgesic, anti-inflammatory, antipyretic and is an inhibitor of platelet aggregation. It inhibits fatty acid cyclo-oxygenase by acetylation of the active site of enzyme and the pharmacological effects of aspirin are due to the inhibition of the formation of cyclo-oxygenase products including prostaglandin, thromboxanes and prostacyclin. Aspirin is prepared by chemical synthesis from salicylic acid, by acetylation with acetic anhydride.
Materials and Apparatus.
Materials needed.
8-10 drops of acetic anhydride. *
0.05-0.10 g of salicylic acid.
3-4 drops of sulfuric acid, concentrated. *
Several drops of 1% FeCl3 solution.
*Use extreme caution and avoid skin contact. Sulfuric acid and acetic anhydride may cause severe burns.
Apparatus needed.
4 test tubes, 13 × 100 mm.
4 stoppers to fit the test tube.
micropipette.
2 beakers, 250 ml, one for hot water bath, one for ice bath.
Ice.
Hot plate.
Filter paper.
Watch glass.
HEALTH AND SAFETY.
General Safety Guidelines in the laboratory.
* Always wear proper eye protection in chemical work, handling, and chemical storage areas. Contact lenses should not be worn in the laboratory. Special precautions should be taken if they are worn.
* Always know the physical and chemical properties of the materials used in an experiment or demonstration (e.g., corrosiveness, flammability, reactivity, toxicity, and stability.)
* Always wear appropriate protective clothing (e.g. lab coats), including shoes with enclosed toe areas. Do not wear high-heeled shoes, open-toed shoes, sandals, or shoes made of woven material. Tanks tops, shorts, or short skirts should not be worn in the laboratory. Disposable aprons are cheap and can effectively protect the body and clothing.
* Confine long hair and loose clothing.
* Always wash hands and arms with soap and water before, or immediately after, leaving the work area. This applies even if you have been wearing gloves.
* Never perform any work when alone in the chemistry laboratory. At least two people must be present and one must be the instructor.
* Never eat, drink, smoke, or apply cosmetics in the laboratory. Fingernail biting or pencil chewing should be discouraged.
* Never perform unauthorized work, preparations, or experiments.
* Never engage in horseplay, pranks, tricks, gags, or other acts of mischief in chemical work areas.
* Never remove chemicals from the work area without proper written authorization.
Safety Guidelines when using chemicals required for the experiment.
* Wear lab goggles throughout the experiment.
* Do not leave the hot plate and boiling water bath unattended.
* Acetic anhydride is a skin and eye irritant in the liquid and vapor states. Avoid contact with skin and eyes. Rinse any part of the body that comes in contact with this chemical. Inform your teacher immediately.
* Concentrated sulfuric acid is a powerful dehydrating agent; handle it with care to avoid contact with skin and clothing. Again, inform the teacher immediately if any contact occurs.
* Dispense both the acetic anhydride and the sulfuric acid to minimize your exposure to both.
PROCEDURE.
Preparation.
. Wash and thoroughly dry the test tube(s).
2. Half fill a beaker with water.
3. Heat the beaker with water to boiling on the hot plate in preparation for the actual synthesis.
4. Obtain ice in the second beaker and add water until it is about 2/3 full. Let it stand until after the heating.
5. Measure the mass of your clean, dry test tube. Record this mass in your lab notebook.
6. Measure an amount of salicylic acid, about the size of a match head into your clean, dry test tube.
7. Measure and record the mass of the test tube and salicylic acid. The mass should be between 0.05 and 0.10 grams.
Synthesis.
. Go to the fume hood, place 8-10 drops of acetic anhydride in the test tube and then add 3-4 drops of sulfuric acid. Be sure your lab partner, if working in pairs, stays at the lab bench to keep watch over the water bath on the hot plate, otherwise, do not leave the water bath on the hot plate.
2. Take the test tube and heat the test tube and contents in the hot (boiling) water bath for approximately 3 minutes.
Purification.
. Remove the test tube from the hot water bath and use the plastic pipette to cautiously add 10 drops of water to the tube.
2. Stopper the test tube and shake it well.
3. Carefully remove the stopper and place the test tube in the ice bath. Allow the tube to remain in the ice bath for at least 5 minutes. Observe and record your observations as it cools.
4. Use a pipette to remove as much liquid as possible from the crystals that have formed.
5. Add enough hot water to just dissolve the crystals.
6. Cool again and new crystals should form.
7. Rinse the pipette and once again use it to remove as much liquid as possible from the crystals that have formed.
8. Place the crystals on a piece of filter paper and place this on a watch glass to dry overnight.
9. After drying overnight, store the product (aspirin) in a cool dry place.
ORIGINAL USES OF ASPIRIN.
Against pain: Aspirin was introduced as a painkiller. After 100 years it remains the "gold standard" remedy against which all new painkillers must be compared. In its usual tablet form it is used for aches and pains, for arthritis and "rheumatism", for headaches, period pains, toothache, the pain of bruises and other injuries, and after dental treatment. In fact, most forms of mild to moderate pain respond quickly to aspirin. It works best when taken early, before the pain has "taken hold".
Exactly how it works against pain is being unraveled by current research. In peripheral tissues, such as skin, muscles and joints, aspirin itself blocks the prostaglandin that is produced in inflamed, infected and injured tissues to cause the sensation of pain. However, aspirin also acts centrally: the salicylate and acetate parts of aspirin's chemical structure (aspirin is acetyl salicylic acid) cross separately into the brain and spinal cord - where they act on prostaglandin in sites in the central nervous system known to be involved in the perception and transmission of pain.
This new knowledge about the way, and where, aspirin works, has led to renewed interest in its use in severe pain - a field previously thought to be occupied only by opiates such as morphine and heroin and similar drugs. Dr. Torsten Gordh, of Uppsala, Sweden, has reported that there are many forms of pain for which aspirin is much more effective than opiates - among them headache, post-operative orthopaedic or ENT surgery, superficial skin or mucosal ulcers, and the pain of secondary cancers in bone. Aspirin also works in tandem with opiates. It is now being used successfully along with morphine or codeine to combat the pain of cancer. For example, it can allow doses of these narcotic agents to be reduced, so that patients are less sedated and can enjoy a better quality of life.
It is now being given as infusions of lysine-acetylsalicylic acid (lysine-aspirin) around the spinal cord ("intrathecally") to patients with intractable cancer pain and severe back pain. In the first study, in 1983 (Devogel et al) a single dose gave relief to 34 patients for between 2 and 27 days (mean 6 days): a second study in 1987 confirmed this benefit in 60 cancer patients (Pellerin).
Aspirin has also been successfully used topically - on the skin - to relieve the pain of shingles. Future uses of aspirin may include a "patch" preparation, to deliver the drug through the skin.
Against fevers: Fevers caused by infections respond well to aspirin because it acts directly on the temperature regulation center in the brain.
Against inflammation: Inflammation, with its classic signs of swelling, redness, local heat, loss of function and pain, is part of the body's reaction to infection or injury. It also occurs as an abnormal reaction in diseases such as rheumatoid arthritis and osteoarthritis.
Aspirin was the first of the "non-steroidal anti-inflammatory drugs"(NSAIDs) now so widely used against arthritis. Although not a cure for arthritis, aspirin can relieve all the signs of inflammation, allowing sufferers to become more mobile and lead more active lives in relative comfort. However this needs medical supervision and higher doses to obtain an anti-inflammatory effect than would be taken for simple aches and pains or a headache.
OBI AGUIYI
AVCE SCIENCE YEAR 2.