Expt. 4

• 3 g Salicylic Acid + 6 mL Acetic anhydride + 5-10 gtts H3PO4

  • Heat the mixture for about 10 mins (water bath)
• After heating, + 20 gtts & 20 mL Dist. Water Cool in ice bath = crystals (if not scratch wall of the flask)
• Filter solid aspirin

  Wash crystals with 2-3 mL chilled water
• Place filter paper on a watch glass

  Dry in an oven (1000C)
• General Steps in Synthesis

  1. Carrying out the Reaction
  2. Isolating the Product
  3. Purifying the Product
  4. Characterizing the product and estimating its purity
• Organic Synthesis

  • Often involves converting 1 functional group to another
  • Involves changing a part of the molecule by design
  • Results in a different molecule often with different physical properties
• Methyl salicylate (ester) —> Salicylic acid (carboxylic acid)
• Acetyl Salicylic acid

  • Carboxylic acid functional group
  • Ester functional group
  • Aromatic group
• IUPAC Name of Acetyl salicylic acid is 2-acetoxybenzoic acid
• Molecular formula of acetyl salicylic acid is C9H8O4
• Physical property of Acetyl Salicylic acid is crystals or crystalline powder
• Color of Acetyl Salicylic acid is colorless or white
• Odor of Acetyl Salicylic acid is odorless
• pH of Acetyl Salicylic acid is 3.5 at 20ºC
• Melting point of Acetyl Salicylic acid is 138-140ºC
• Boiling point of Acetyl Salicylic acid is 140ºC
• Water solubility of Acetyl Salicylic acid

  1. boiling water = 1:1
  2. at 35ºC = 0.03:1
  3. at 15ºC = 0.01:1
  4. (slightly soluble in water)
  5. soluble in alcohol (1:5), chloroform (1:17), ether (1:15)
• 1830s - A Scottish physician found that extracts of willow bark relieved symptoms of acute rheumatism.
• 1840s - Organic chemists working with willow (Salix sp.) bark and flowers of the meadowsweet plant, Spirea (Filipendula ulmaria), isolated and identified the active ingredient as salicin (salix = Latin word for willow).
• 1870 - A professor demonstrated that salicin was converted into salicylic acid in the body. However, the compound caused severe irritation of the lining of the mouth and stomach.
• 1890s - Felix Hoffmann of the Bayer Company in Germany made aspirin which was found to have good medicinal properties, low membrane irritation and a reasonable taste.
• ”A” in aspirin means acetyl
• ”spir” in aspirin means spirea plant (which yields salicin)
• ”in” in aspirin is a common suffix for medications
• Biological activity of ASA

  • Analgesic
  • Antipyretic
  • Anti-inflammatory (anti-rheumatic)
  • Anti-platelet — to prevent MI and stroke (80 mg dose)
• Mechanism of Action

  • Inhibition of synthesis and release of prostaglandins
• COX means cyclooxygenase
• Membrane phospholipids becomes arachidonic acid through phospholipase A2
• In COX-1 (constitutive), prostaglandins is associated with

  • GI mucosal integrity
  • Platelet function
  • Renal function
• In COX-2 (inducible), prostaglandins associated with

  • pain
  • fever
  • inflammation
• Salicylic acid forms with Fe3+ ions violet-blue complexes
• The intensity of the colour depends on the salicylic acid concentration in a sample.
• A sample of pure aspirin should not exhibit any color change.
• Chemical tests of Acetyl salicylic acid

  • Reaction with FeCl3 TS
  • pH determination
• pH determination of acetyl salicylic acid

  • pH of Aspirin =3.5 at 20ºC

  • Ka =2.8 x 10-4 at 25ºC
• Hydrolysis product of Aspirin (prodrug)

  • Salicylic acid – active metabolite
  • Acetic acid
• Common Side Effects of Aspirin

  • digestive upset such as:
  • heartburn
  • nausea
  • bloating
  • diarrhea
  • stomach pain
  • gastrointestinal bleeding
  • peptic ulcers
• Taking aspirin for long periods of time may cause:

  • Ringing in the ears or hearing loss
  • Unusual sweating
  • Headache, dizziness, dimness of vision, confusion, fever, or drowsiness
  • Rapid breathing and rapid heartbeat
  • Thirst, nausea, vomiting, or diarrhea
• Aspirin has been linked with Reye's syndrome

  • Fatal -- liver and brain swelling
  • Children and teenagers recovering from chickenpox or flu-like symptoms should NEVER take aspirin.
• Side effects of aspirin