DR. EDDY

CHEM 2445 - Aspirin

Aspirin

Chapter 41, p 529Acylation of salicyclic acidMacroscale Procedure, p 533Using product for next experiment

SAVE THE ASPIRIN

History of Pain Relief

Salicin isolated from willow bark and poplar bark Used as analgesic

Salicyclic acid developed from Kolbe synthesis (1860) Attacks mucoid

membranesAspirin found to

minimize mucoid irritation (1869, 1874)

Annalen der Chemie und Pharmacie, 1860, 113, 125Chem. Rev., 1957, 57, 583

Rev. Med. Interne, 2000, 21, 8

Medicinal Effects of Aspirin

Analgesic, antipyretic (fever reducer), anti-inflammatory

Interacts with COX-2 Acylates terminal amine Covalent modification of protein, irreversible inhibition

Aspirin Resistance Can prolong bleeding time Associated with platelet thromboxane A2 and 12-

hydroxyeicosatetraenoic acid (12-HETE)Lowers risk of stroke, heart attack and vascular

death with low dose aspirinCan cause aspirin-induced asthma in adultsBMJ, 2008, 336, 195

Can. J. Cardio., 1995, 11, 221Lancet, 1999, 353, 2179Gastroenterology, 2003, 124, 47BMJ, 2004, 328, 434

Synthesis of Aspirin

Ester synthesisWithout a catalyst, reaction takes prolonged

timeFour catalysts

H2SO4

BF3•OEt2

Pyridine NaOAc

Ester Synthesis

H2SO4 and BF3•OEt2 Mechanism

Pyridine Mechanism

Sodium Acetate Mechanism

Procedure

Four test tubes 0.2 g NaOAc 5 drops pyridine 5 drops sulfuric acid 5 drops BF3•OEt2

Record time required for 4°C increaseHeat in hot water bath for 5 minutesPour all 4 tubes into flask containing 50 mL waterCool and induce crystallizationVacuum filterRecord mp and weightTest solubility in toluene and waterSAVE ALL ASPIRIN

IR of Aspirin

NMR of Aspirin

Pre-Lab Things

Include Table of chemicals Hazards Reactions Mechanisms

Make a note to save the aspirin

Post-Lab Things

Things to discuss Difference in mechanisms

Which is more effective, and why? What would happen if you didn’t destroy excess acetic

anhydride? Other acylating agents possible?

Getting out on time

Work in pairs One person do bases, one acids Have water bath heating while waiting

SAVE THE ASPIRIN