The Synthesis of a Medicinal Agent- Aspirin, Lecture notes of Chemistry

Download The Synthesis of a Medicinal Agent- Aspirin and more Lecture notes Chemistry in PDF only on Docsity! The Synthesis of a Medicinal Agent- Aspirin By Walter Scharf and Charles Malerich Natural Sciences/Chemistry Baruch College New York, NY 10010 Introduction Salicylic-acid-containing compounds derived from willow bark have been in use for hundreds of years as antipyretic (fever-reducing), analgesic (Pain killing), and anti-inflammatory agents. It was eventually discovered that salicylic acid is the portion of these molecules responsible for the therapeutic effect. Two ester derivatives of this acid, synthesized as shown, are currently in common medicinal use: methylsalicylate (oil of wintergreen) for external applications and acetylsalicylic acid (aspirin) for internal consumption. The particular derivatives are chosen for their effectiveness in penetrating the physiological environment in the respective application-the skin or the intestines. Once within the body tissue, both compounds are hydrolyzed to a salicylic acid, the active agent. This experiment will demonstrate the preparation of aspirin. Aspirin is superior to salicylic acid for oral dosage in that the latter is very bitter, and causes stomach upset. The aspirin possesses these properties to a markedly lesser degree and passes through the stomach largely unchanged, undergoing hydrolysis only in the small intestine and after absorption in the blood stream. This temporarily masking of a physiologically active compound, to facilitate oral ingestion or prevent decomposition during transport to the site of activity within the body, is a very common strategy in drug design. The esterification reactants written above do not proceed fully to completion. A convenient way to obtain complete reaction in the preparation of an acetate ester is to use acetic anhydride. The reaction is catalyzed by concentrated phosphoric acid. Excess acetic hydride may be used in this reaction as the un-reacted portion is hydrolyzed after reaction is complete with water, The acetic acid is produced is removed by filtration of the acetic acid- water solution to yield aspirin crystals. Trace amounts of salicylic remaining are removed by recrystallization from an ethanol/water solvent pair. . Purification of a solid by crystallization from a solvent-pair Occasionally a mixture of two solvents (solvent-pair) is more satisfactory than a single solvent for recrystallization. Such solvent-pairs are made up of two miscible liquids, one of which dissolves the substance readily and another which dissolves it very sparingly. Examples of solvent-pairs are: ethanol and water, glacial (pure) acetic acid and water, diethyl ether and petroleum ether, and benzene and ethyl acetate. A typical procedure in using a solvent pair such as ethanol and water, is to dissolve the substance in ethanol at the boiling-point and add water dropwise, with shaking or stirring, until a faint turbidity persists in the hot solution. A few drops of ethanol are then added until the solution clears. The hot solvent mixture is then not quite saturated with the solute and is treated subsequently in the usual way (decolorized with charcoal (if necessary), filtered hot (if treated with charcoal), cooled, filtered, and washed.).