Synthesis of Aspirin

History
First synthesized by Charles Gerhardt in 1853 from salicylic acid and acetic anhydride

In 1893, Felix Hoffmann (Bayer company in Germany) reinvestigated the synthesis reported by Gerhardt forty years earlier
Bayer Company obtained a patent on acetylsalicylic acid Bayer coined the name Aspirin for their new product to reflect its acetyl nature and its natural occurrence in the Spiraea plant

Biological Activity
Analgesic - painkiller Antipyretic - fever reducer

Anti-inflammatory - inhibition of the synthesis of prostaglandins

Uricosuric - enhances the elimination of uric acid

Materials and Reagents

Hexane Methanol Distilled H2O Salicylic acid Erlenmeyer flask Beaker Thermometer Iron stand Vacuum flask Bchner funnel Filter paper

Acetic Anhydride
Concentrated H2SO4

Set-up and Equipment

Procedure
Selection of recrystallizing solvent The Synthesis

Purification

Choosing the Recrystallizing Solvent

1 hexane
1 2 3

2 water 3 - methanol

+ ~2-3 mg of standard aspirin Note the solubility Solvent

SOLUBILITY
Room temperature High temperature

Behavior at Low Temperature

Hexane
Soluble

Insoluble

Water Methanol

Cool in an ice bath

Heat in a water bath Note the solubility

Soluble

Insoluble

Cool in an ice bath

Properties of a Recrystallizing Solvent

The compound should be very soluble at the boiling point of the solvent and only sparingly soluble in the solvent at room temperature.

The unwanted impurities should be either very soluble in the solvent at room temperature or insoluble in the hot solvent.

The solvent should not react with the compound being purified.

The solvent should be volatile enough to be easily removed from the solvent after the compound has crystallized.

The Synthesis

The Mechanism (O-acylation)

ACETIC ANHYDRIDE

SALICYLIC ACID

ACETYLSALICYLIC ACID

Recrystallization Purification method

Rapid and convenient way of purifying a solid organic compound

The material to be purified is dissolved in the hot appropriate solvent

As the solvent cools, the solution become saturated with respect to the substance, which then crystallize

Impurities stay in solution

Assessment of Result
Examine the following:
Physical appearance physical state, color, odor, texture, etc. Melting point determine the melting point range Percent yield calculate the yield of the reaction based on the experimental result and stoichiometry of the reaction Infrared spectra identify the functional groups present in the spectra and compare the obtained spectrum with the reference spectrum

Assessment of Result
Physical appearance

physical state: ________________

color: _____________

odor: _____________

texture: ___________

Assessment of Result
Melting point
the melting point of a compound is a criterion for purity as well as for identification. pure, nonionic, crystalline organic compound usually has a sharp and characteristic melting point.

very small amounts of miscible impurities will produce a depression of the melting point and an increase in the melting point range.

acetylsalicylic acid: 136C

O R G A N I C C H E M I S T R Y

Assessment of Result
Percent yield

2.0 g

4.0 mL
d = 1.082 g/mL ?

Experimental yield: determine experimentally Theoretical yield: calculated from the limiting reagent Percent yield:
O R G A N I C C H E M I S T R Y

Assessment of Result
IR Analysis
A

Assessment of Result
IR Analysis

10

6 PPM

10

6 PPM