The Marquis reaction proceed by the condensation of drug molecules, yielding carbocations or larger unsaturated compounds which are colored. The reaction is selective toward activated aromatic cycles.
The drug molecule (1) undergo an electrophylic substitution by the protonated formaldehyde (2). The carbocation (3) obtained reacts with another drug molecule yielding a dimer (4). The dimer is subsequently oxidized (concentrated sulfuric acid behaves as an oxidizer) to give a stabilized carbocation (5). This last compound is colored and is responsible for the color observed.
The regioselectivity of the addition of formaldehyde is determined by the usual selectivity rules for electrophilic substitutions.
The previous mechanism must be refined for each compound. Below are given two examples for which the mechanisms have been elucidated.
The reaction in the case of morphine differs sligthly from the previous scheme since two formaldehyde molecules (in red) are involved in the condensation, thus forming a cycle. Subsequent oxidization of the cycle leads to the formation of the purple/violet carbocation.
The case of methamphetamine fits perfectly with the general mechanism given above. The colored compound and produces an orangish color.There is also a possibility of condensation in the ortho position. However, the latter is much more strained and thus the amount produced is far less inferior to that of the depicted carbocation, leading to less polymerization and thus a clearer color.
The previous examples given show an unambiguous colored product. However, this is not always the case. For many molecules, there are multiple potential condensation sites, therefore leading to multiple colored compounds. Polymerization can also occur if the aromatic cycles are sufficiently reactive (for example with MDMA
In such cases, the compound tested will give a dark brown or black coloration, resulting from the multiple different absorption wavelengths. This situation is the same as when mixing many paints of different colors: the resulting mixture is dark brown.
The color obtained depends on the composition of the starting reagent. Pre-made kits availabe over the internet are prepared the same way and thus the results from these tests are reproductible. However, hand made reagents will have some small variations in their composition, leading to slightly different results (shades of color will vary). For example a reagent containing more formaldehyde will induce more polymerization thus a darker coloration.
The presence of adulterants in the tested product may also affect the resulting coloration:
- Firstly, the adulterants may react by themselves with the reagent adding their own coloration to the result.
For example if some sugars are present (lactose for example), they will caramellize in the presence of sulfuric acid, thus producing a brown coloration. This is not the result of a marquis reaction, but only the reaction of the sugar with sulfuric acid.
Another case is if some aromatic compounds are present (like acetaminophen
), they will undergo a marquis reaction, therefore yielding their own coloration which will superpose to give the resulting coloration.
- Secondly, the adulterants may react with the drug forming cross condensed products yielding a different color.