Synthesis of acetylsalicylic acid (Aspirin):
O
O
O
H
O
O
H
O
+
H
O
+
H
O
O
+
O
O
H
O
Salicylic acid
Acetic anhydride
o-acetylsalicylic acid
• Synthesis / working-up
• HPLC (reaction control /purity control)
Acetic acid
Experimental arrangement:
Mechanism of the reaction:
• addition-elimination- mechanism
electrophilic carbon
low electron density
O
O H
O
δO
H
+
δ+ O
O
+
O
O H
O
H
O
+
O
lone pair
nucleophile
high electron density
O H
1. step: Activation of the electrophile
• increase in reactivity
2. Step: Addition reaction
3. Step: Elimination reaction
Reaction control:
• using the HPLC to follow the course of the reaction
• take a sample every 20 minutes
(before and after the additon of sulphuric acid)
• stop the reaction when no further formation of the acetylic salicylic acid
is observable
Working-up: Recrystallisation
• Recrystallisation is a fundamental technique used
to purify solid compounds
Recrystallisation is based on the principles of solubility:
• compounds tend to be more soluble in hot solvents than
they are in cold liquids
• if a saturated hot solution is allowed to cool, the solute is
no longer soluble in the solvent and forms crystals of pure
compound
• impurities are excluded from the growing crystals and the
pure solid crystals can be separated from the dissolved
impurities by filtration
Characterisation:
• HPLC
• melting point determination
Melting point determination:
• the determination of melting points is one of the oldest identification
• fast and simple tool
• changes from a solid to a liquid state
• pure crystalline substances have a clear, sharply defined melting point
• a pure substance melts at a precisely defined temperature, characteristic
of every crystalline substance
• to obtain a first impression of the purity of a substance
• small quantities of impurities change the melting point
Determination of the yield:
• you started with 0,05 mol Salicylic acid and acetic anhydride
• if you have a yield of 100% you should obtain 0.05 mol aspirin
• 0.05 mol * molecular weight of aspirin = X g
• balance out your dried product
• calculate your aspirin yield in %
Sources of risk:
Acetic anhydride:
Sources of risk:
Acetic anhydride:
R10 Flammable
R20/21 Harmful by inhalation and in contact with skin
R34 Causes burns
Salicylic acid:
Salicylic acid:
R22 Harmful if swallowed
R41 Risk of serious damage to eyes
Sulphuric acid:
R35 Causes severe burn
Sulphuric acid:
R35 Causes severe burn