Aspirin & Salicylic Acid – Ferric Chloride Complexes

The major hydrolysis product of aspirin is salicylic acid, which can form coloured complex with neutral FeCl3. Aspirin is incapable of forming this complex.  Explain this process.

First marketed under the trademark Aspirin^® in 1899,acetylsalicylic acid quickly attained a worldwide reputation as anon-prescription pain relief drug.  Even today it is one of the most widely used drugs in the treatment of headaches, body and muscle pains, arthritic pain, and more.

Salicylic acid is the major hydrolysis product of acetylsalicylic acid, as shown below in Equation 1, and its detection and quantification in samples containing acetylsalicylic acid can be important for a number of reasons.  First, because among the biggest concerns relating to pharmaceuticals is the degradation of the active ingredient during the shelf life of the drug.  Second, the production of counterfeit drugs is a problem of growing concern.  Poor or unregulated synthesis of acetyl salicylic acid can result in contamination with significant amounts of unreacted salicylic acid, which can have adverse health effects.

A simple but effective method of detection for free salicylic acid is based on the differing co-ordinating capacity of salicylic compounds with the trivalent iron cation, Fe⁺³.  Asa transition metal, co-ordination with different salicylic compounds can produce various highly coloured solutions for simple qualitative analysis.  Further, preparation of calibration standards can be performed to allow quantitative spectrophotometric analysis.

The analysis of phenols with ferric chloride is a widely known test.  Phenol groups form a purple complex with the Fe⁺³ cation, with the depth of the colour related to the co-ordination capacity of the phenol group.  Acetyl salicylic acid and salicylic acid both contain phenol groups, but that in acetyl salicylic acid is bonded to an acetyl group, reducing its co-ordination capacity.  Thus while both compounds will form a coloured complex with Fe⁺³, acetyl salicylic acid forms avery slightly yellow-orange coloured complex, but salicylic acidforms a highly coloured deep purple complex.

Most transition metal ions act as Lewis acids by forming co-ordinate covalent bonds with ligands.  Such ions bonded to ligands are referred to as complex ions, and these can be cationic,anionic, and even neutral.  Complex ions are usually coloured,the colour depending on which transition metal and which ligands are present.

Substances appear coloured if they absorb some wavelength or wavelengths of light corresponding to the visible region of the electromagnetic spectrum (light with a wavelength of between about400 – 700 nm) and transmit or reflect other wavelengths within this region.  This absorption of specific wavelengths occurs because of the quantised electronic levels within molecules, which allow only the absorption of specific energies of light, at energies corresponding to the difference between electronic levels in the molecule.

In the case of Fe⁺³, octahedral complexes are formed in aqueous solution, as illustrated by Figure 1 below.  Under Crystal Field Theory bonding between the transition metal atom and the ligands is ignored.  It is assumed that the ligands are point charges, and the result is an octahedral field; the effect of this field on the d-orbitals is then calculated. 

In uncomplexed Fe⁺³ all the d-orbitals are at the same energy level.  Under Crystal Field Theory the presence of ligands will alter the energy levels of some of the d-orbital showever.  In octahedral complexes ligands approach the central metal atom along the x-, y-, and z-axes, so the orbitals dxy, dxz,and dyz will be filled due to covalent bonding with the ligands.  The orbitals dx²-y² and dz² will then have higher energy due to repulsion with the filled orbitals, as illustrated in Figure 2 below.  The energy difference between the two groups of d-orbitals is called the Crystal Field Splitting, D, and in the case of Fe⁺³ complexed with phenolic compounds this corresponds to wavelengths in the visible light region.

The complex formed between salicylic acid ligands and Fe⁺³ results in crystal field splitting with an energy difference corresponding to light which appears deep purple; the complex between acetyl salicylic acid ligands and Fe⁺³results in crystal field splitting with an energy difference corresponding to light which appears yellowish.  Of course,the intensity of the light depends on the concentration of the complex present in solution in accordance with the Beer-Lambert Law, and a standard spectrophotometric test for salicylic acid -Fe⁺³ complexes involves measuring absorbance at a wavelength of ~540 nm.

In the case of quick qualitative detection of acetyl salicylic acid and salicylic acid a simple visual test will suffice.  Bythe addition of an excess of Fe⁺³ in some suitable form,such as ferric chloride, to a test solution complexes ofFe⁺³ will be formed.  If the solution turns a deep purple colour, then salicylic acid is present in the testsolution.  If it turns a yellow-orange colour, then no salicylic acid is present, and it can be assumed that only acetyl salicylic acid is present in the test solution.

This allows a quick visual test of samples of aspirin -commercial pharmaceutical preparations of aspirin should not contain any significant quantity of salicylic acid, but preparations of acetyl salicylic acid made in a university lab will contain unreacted salicylic acid.