CHEM 2445 - Aspirin

DR. EDDY

Aspirin
Chapter 41, p 529
Acylation of salicyclic acid
Macroscale Procedure, p 533
Using 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
membranes

Annalen der Chemie und Pharmacie, 1860, 113, 125

Chem. Rev., 1957, 57, 583

Aspirin found to

minimize mucoid
irritation (1869, 1874)

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 12hydroxyeicosatetraenoic acid (12-HETE)

Lowers risk of stroke, heart attack and vascular death

with low dose aspirin

Can cause aspirin-induced asthma in adults
BMJ, 2008, 336, 195
Can. J. Cardio., 1995, 11, 221
Lancet, 1999, 353, 2179
Gastroenterology, 2003, 124, 47
BMJ, 2004, 328, 434

Synthesis of Aspirin
Ester synthesis
Without a catalyst, reaction takes prolonged time
Four catalysts

H2SO4

BF3OEt2

Pyridine
NaOAc

Ester Synthesis

H2SO4 and BF3OEt2 Mechanism

Pyridine Mechanism

Sodium Acetate Mechanism

Procedure
Four test tubes

0.2 g NaOAc
5 drops pyridine
5 drops sulfuric acid
5 drops BF3OEt2

Record time required for 4C increase

Heat in hot water bath for 5 minutes
Pour all 4 tubes into flask containing 50 mL water
Cool and induce crystallization
Vacuum filter
Record mp and weight
Test solubility in toluene and water
SAVE 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 didnt 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