Synthesis of Aspirin Lab Procedure PDF

Pharmacy Technologies Departmen SECOND STAGE Lab 3 synthesis of aspirin By Assistant lecturer Husam Adel Mohammed...

Pharmacy Technologies Departmen SECOND STAGE Lab 3 synthesis of aspirin By Assistant lecturer Husam Adel Mohammed Teeba Saleh Kadhim  Preparation of aspirin It is 2-acetyl salicylic acid or 2-acetoxy benzoic acid. Molecular formula is C9H8O4, M wt is 180.15. Characteristics: It is colorless crystals or white crystalline powder , odorless with slightly acid taste. Solubility: It is slightly soluble in water (1:300) at 25 , (1:100) at 37 more soluble in organic solvent, e.g. ether , ethanol, chloroform, ….. etc. Stability: In the form of crystals or powder, ASA is stable in dry air , but in contact with moisture, it degrades by hydrolysis to both SA and acetic acid (HAc), through base catalysis of the attack of water molecule by carboxylate anion. COOH COOH + H2O + CH3COOH OH OCOCH3 Mechanism: O O H C C O O H COOH OH slow OH fast + CH3COOH O C CH3 O C CH3 OH O O  Extensive decomposition of aspirin tablets is easily recognized by the odor of acetic acid , partially degraded aspirin tablets are sometimes seen with needles SA on their surface, a result of sublimation of SA. The melting point of ASA is not a reliable indicator of its purity because it partly decomposes on heating (137-143 ). Synthesis of aspirin: Method 1: OH OCOCH3 O O COOH COOH C C + H3C O CH3 + CH3COOH acetic anhydride acetic acid SA aspirin Mechanism of reaction: 1- Protonation of the oxygen of carbonyl group: 2- Protonation of central oxygen to give oxonium ion Method 2: O OH O C CH3 COOH O COOH N + H3C C Cl + pyridine acetyl chloride N HCl aspirin pyridine chloride Identification test of aspirin :- Ferric chloride test; The presence of phenolic group in a compound is indicated by the formation of violet iron complex when treated with ferric chloride solution Aspirin ------------► give –ve result with FeCl3 due to absence of phenolic group Salicylic acid--------► + ve result Notes: Method 1 is used mostly because acetic anhydride is cheap, readily available, easily handled and doesn't form corrosive HCl gas. The reaction of acetylation is in the following order: Acetyl chloride > acetic anhydride > acetic acid On the other hand, acetylation of SA using acetyl chloride is very vigorous and will produce HCl gas which is corrosive to the respiratory tract. In this method, pyridine base is used because the unshared pair of electrons on the N will react with HCl and form pyridine chloride. On the other hand , pyridine base is teratogenic agent and air pollutant; therefore, we avoid this method of preparation. Procedure :- 1- Place 1g of SA into a dry small flask. 2- Add 2 ml of acetic acid. 3- Add 1-2drops of conc. H₂SO₄, cautiously. 4- Put on heater stirrer with stirring until SA crystals get into solution. 5- Cool, white crystals of aspirin will appear. 6- Add little water then filter. Notes: 1- If crystals of ASA remain in the reaction flask, use a little filtrate to wash them into the funnel. 2- Acetic anhydride (an effective acetylating agent) will be used to convert SA to ASA and to serve as a solvent for the reaction. 3- If crystals of ASA didn't appear after cooling, water is added to destroy the excess acetic anhydride (converting it to water - soluble acetic acid). 4- Acetic acid is not added because it enhances the hydrolysis of ASA. The same is in case of adding excess conc. H2SO4.