Synthesis, Purification, and Analysis of Aspirin
Aspirin (acetyl salicylic acid) is a salicylic acid derivative and is one of the most popular and commonly used drugs. Other derivatives of salicylic acid include: oil of wintergreen (methyl salicylate) and salol (phenyl salicylate). See the following table for structures, properties, and uses for these compounds:
Structural Formula
/ Name(common name) / Molecular Name Molecular Medical Uses Other Uses
Weight
/Medical Uses
/ Other UsesSalicylic Acid / 132.12 / Antimicrobial
(external use) / Food Preservative
Preparation of dyes
Acetylsalicylic Acid Analgesic
(aspirin) / 180.16 / Analgesic
Antipyretic
Antirheumatic
Methyl Salicylate
(oil of wintergreen) / 152.15 / Counterirritant / Perfumes
Candy Flavoring
Phenyl Salicylate
(salol) / 214.21 / Analgesic
Antipyretic
Antirheumatic
Intestinal Antiseptic / Polymers
Laquers
Waxes
Adhesives
Polishes
Suntan Oil
Methyl salicylate is somewhat toxic in large amounts, and normally is used only in salves that are applied externally. Aspirin and salol are used internally. Aspirin is one of the few drugs that has very few undesirable side effects, even with continued use. Some people develop allergies to salicylic acid derivatives and cannot use them. Aspirin belongs to a class of compounds called chelating agents, which are compounds capable of seizing and holding a metallic ion in a claw-like grip. The action of aspirin in relieving pain and reducing fever may be related to its ability to remove excess copper from the body by chelating with copper and transporting it back to the body cells from which it was lost.
Two functional group reactions in this series are significant. First, the carboxyl group of -COOH is acidic in nature. The carboxyl group reacts with dilute sodium bicarbonate to release carbon dioxide and to form the sodium salt of the organic acid. In general, carboxylic acids which are not water soluble are converted to their water soluble sodium salts by the addition of sodium bicarbonate which acts as a base as can be seen in the following reaction:
R-COOH + NaHCO3 ® R-COONa + CO2 + H2O
Second, the phenol group reacts with 1% aqueous ferric chloride reagent to give a purple complex. Phenol is a weak acid and is in equilibrium with the phenolate ion according to the following reaction:
+ H2O / « / H3O+ +Thus, a sensitive test for excess or unreacted phenol is the reaction in which the phenolate ion forms the purple [ Fe(phenolate)6 ] –3 complex.
6 phenol + Fe+3 « Fe(phenolate) 6-3 + 6 H+
It is the conjugate base of phenol, in other words the phenolate ion, which is complexed or bonded to the iron to form the purple iron compound. Phenol is a much weaker acid than the carboxylate group.
Aspirin is prepared by the formation of an ester. This ester is formed between the phenolic group of salicylic acid and acetic anhydride as is shown below:
salicylic acid / + H3COHmethanol / ∆
H2SO4 / methyl salicylate / + H3O+
water
ADDITIONAL INFORMATION:
Acetylating agents other than acetic anhydride can be used; however, acetic anhydride is used because it is inexpensive and is not too difficult to handle safely in the laboratory. Aspirin is a white solid and is almost insoluble in water (only 0.25 g will dissolve in 100 ml of water @ 0 ºC). Thus it can be separated from the reaction mixture by crystalliazation and filtration. Sulfuric acid is used as a catalyst (a substance that alters the rate of a chemical reaction without being permanently changed itself). Oil of wintergreen is made by reacting salicylic acid with methyl alcohol (methanol) in the presence of sulfuric acid catalyst.
PRECAUTIONS:
The following precautions are necessary in using the chemicals in this lab:
- Acetic anhydride is irritating to the skin and eyes. Use with adequate ventilation.
- Concentrated sulfuric acid is extremely irritating to the skin and eyes, reacts violently with water, and destructive to clothing! Handle with extreme care.
- Methanol is a very flammable liquid. Breathing the vapor for short periods even in low concentration is dangerous. Swallowing small quantities of the liquid can cause blindness or death. Use with adequate ventilation.
1. Preparation of Aspirin
Weigh (accurately to 0.01 g) approximately 6 g of salicylic acid in a 125 ml Erlenmeyer flask. Add 8 ml of acetic anhydride to the salicylic acid in the Erlenmeyer flask. CAUTION...add 10 drops of concentrated sulfuric acid to the mixture, swirl the flask gently, and heat the flask in a beaker of boiling water (see diagram) for 15 minutes (stirring in the final stages may be necessary, but do not use a rubber policeman while the mixture is hot). If the solid does not dissolve, heat the mixture for an additional 10 minutes. Remove the flask from the water bath and add 25 ml of ice water to the flask. Set the flask in an ice bath until crystallization appears to be complete (approximately 10 minutes). While the flask is in the ice bath, set up vacuum filtration apparatus. Once the aspirin mixture has cooled, separate the crystals from the liquid by vacuum filtration. RINSE THE FLASK WITH SMALL PORTIONS OF ICE WATER AND TRANSFER THE RINSE TO THE FILTER.
2. Recrystallization of the Aspirin (Purification)
Recrystallize the aspirin by transferring the crystals from the filter paper to a 100 ml beaker. Add 20 ml of ethanol and warm the mixture in a hot water bath until all crystals have dissolved. Then pour 50 ml of warm water into the alcohol/aspirin solution. Allow the mixture to stand for a few minutes and then place the beaker into an ice bath to complete recrystallization.
Filter crystals by vacuum filtration again. Wash any crystals remaining in the beaker with ice water to transfer them to the filter. To facilitate drying the crystals, use a rubber policeman to spread and stir the aspirin on the filter paper while vacuum is on. Transfer the aspirin and filter paper from the Büchner funnel to a larger piece of filter paper. Place this on a paper towel to dry (these may be stored in lab locker overnight). When aspirin is completely dry, transfer crystals to a pre-weighed sample bag and record the weight of aspirin recovered. Calculate theoretical and percent yields of aspirin.
3. Functional Group Tests for Aspirin
A. Ferric Chloride Test - Dissolve a small amount ( ~ 0.1g ) of the aspirin prepared in this experiment in ~ 25 ml of distilled water by heating (not boiling) until the crystals dissolve. Do the same with a similar amount of commercial aspirin. Cool and add 2-3 drops of ferric chloride solution to each of the aspirin solutions. Record observations and show the instructor the samples. What conclusions can be drawn?
B. Sodium Bicarbonate Test - Place a small amount (about the size of a small pea) of the prepared aspirin in a clean, dry 50 ml beaker. Add a few drops of 5% sodium bicarbonate solution to the aspirin and record observations. Do the same with the commercial aspirin. What conclusions can be drawn?
4. Melting Point Tests for Aspirin
Place a small amount of aspirin powder into a capillary tube for melting. An oil (wax) bath will be used to heat the aspirin sample since its melting point is greater than the boiling point of water. See instructor for procedure used in this determination.
As in all melting points, a range of temperature will be recorded for the mp of aspirin.
5. Volumetric Analysis of Aspirin (Lab Prepared)
Accurately ( to nearest 0.001g ) weigh approximately 0.3 g of the well-dried aspirin sample into a clean, dry 50 ml beaker and dissolve it in about 10 ml of methanol. After the aspirin sample is completely dissolved in the methanol, quantitatively transfer this mixture to a clean 250 ml Erlenmeyer flask (rinsing contents of the beaker into the flask with 3 or more small portions of distilled water). Add 20 ml distilled water, 3-5 drops of phenolphthalein indicator, and titrate the aspirin sample with Standardized NaOH solution. Record this data and repeat the procedure with at least 2 more aspirin samples. The reaction that occurs in the neutralization of the carboxylate group of the aspirin is as follows:
+ OH- ® / + H3O+Volumetric Analysis of Aspirin (Commercial Aspirin)
Commercial aspirin tablets contain 5 grains of aspirin (1 grain = 0.06479 gram). Weigh an aspirin tablet to the nearest 0.001 g, transfer the tablet to a 250 ml Erlenmeyer flask, add ~ 10 ml of methanol, and pulverize the tablet with a large stirring rod. Once the tablet is crushed, rinse stirring rod with a small amount of methanol and remove it from the flask. Swirl the flask for several minutes to aid dissolution of the aspirin (this powder will not completely dissolve since some of the buffers and builders do not dissolve). Add ~ 25 ml distilled water, 3-5 drops of phenolphthalein indicator, and titrate as was done with the synthesized aspirin sample. Record the data and repeat this procedure for at least 2 more aspirin tablets.
Name______
Synthesis, Purification, and Analysis of Aspirin
Data:
Mass of Salicylic Acid Used...... ______
Mass of Aspirin Recovered...... ______
Theoretical Yield of Aspirin...... ______
Percent Yield of Aspirin...... ______
Melting Point of Your Aspirin...... ______
Melting Point of Aspirin...... ______
Calculations:
Test
/Your Aspirin (observations)
/Commercial Aspirin (observations
Ferric ChlorideTest
Bicarbonate
Test
Conclusions:
Volumetric Analysis Of Aspirin Name______
YOUR ASPIRIN SAMPLE
Titration Data / Trial 1 / Trial 2 / Trial 3 / Trial 4Mass of sample
Molecular weight of aspirin
Final buret reading
Initial buret reading
Volume of NaOH used
Normality of NaOH standard
Average Molecular Weight of Aspirin Sample ______Percent Error______
COMMERCIAL ASPIRIN SAMPLES
Titration Data / Trial 1 / Trial 2 / Trial 3 / Trial 4Mass of aspirin tablet
Mass of pure aspirin in tablet
Final buret reading
Initial buret reading
Volume of NaOH used
Normality of NaOH standard
Percent aspirin in aspirin tablets ______Percent Error______
Calculations: