Sunday, November 27, 2011

Camphor and Rivanol (Ethacridine Lactate) - An interesting reaction

Two days ago, while trying to clean a pimple with an antiseptic camphor solution, I accidentally used ethacridine lactate (Rivanol) instead. After realizing this, instead of first cleaning the rivanol stain and then applying the camphor, I directly cleaned it with camphor using a cotton pad. Suddenly a new white layer formed at the contact surface between the two layers of substance. The occurrence of a chemical reaction was obvious, and after repeating the experiment in lab conditions, I tried to understand the formation of this new product.


Camphor structure


Rivanol structure
 

As far as my chemistry knowledge could tell, camphor is a tricyclic ketone while ethacridine is a heterocyclic compound with two amino groups. Maybe, what happened was an amino-carbonyl condensation with the elimination of one molecule of water, I thought.

But then another question came to my mind. If so, which one of the two amino groups was the one responsible for the reaction? Which one would be more reactive? And last but not least, how would the nitrogen atom influence the occurence of the reaction?

What happened


Well, let's first consider all the possible occurring reactions. There are three main possibilities. One of them, the amino group on the eccentric ring would suffer an amino-carbonyl intermolecular condensation. The second scenario is the amino group on the heterocyclic ring undergoing the same process. Last but no least, the third possibility includes both groups reacting with camphor.

Scenario I

Scenario II

Scenario III

Obvious to me, was the fact that the heterocyclic group was more reactive than the eccentric one for two reasons. One of them is the fact that the inner ring is less aromathic than the outer ones, therefore more reactive.

The second reason involves the electronic effects applicable for the substance, more precisely the static inductive effects for the ethacridine lactate and the π electron displacements in the double bond of camphor.

Electronic effects in camphor

Firstly, we will take camphor. The massive hydrocarbon radical in C8H14C=O generates a rather strong -I (electron attracting effect) towards the Oxygen atom. This happens due to the fact that Oxygen is more electronegative than Carbon, having a tendency to attract electrons. Due to the same reason, the π bond of the double bond, composed of two electrons is attracted more towards oxygen. Therefore, oxygen develops a  δ- partial charge, while carbon is doing the opposite, accumulating  δ+.

Electronic effects in rivanol

While talking about rivanol, we must take two effects into consideration. One for the left outer ring, and one for the central ring. For the central ring, the positive charge of the Nitrogen atom attracts electrons greatly, therefore, a -I attracting inductive effect is felt by the heterocyclic ring. At the same time, the amino group charges with δ+ making it more electrophilic, thus more reactive.

On the other hand, the outer amino group undergoes the opposite process. The outer phenyl ring, has an aromathic nature, electrophilic by definition. In this case, a very small -I effect is affecting the -NH2 group, thus accumulating a small δ- partial charge.

Out of the two possible reaction loci, after the previous analysis of the effects in both substances, we can easily draw the conclusion that the locus on the inner ring would be far more plausible for the reaction to occur there, than the other one. In other words, probably, all three reactions occur, but the most probable one would be the one in scenario I as shown below:

The real preponderant reaction

The New Compound


The new compund was a precipitate, initially yellow in appearance, but only due to ethacridin lactate coloration in the test tube.

Before and after the reaction

In fact, after subsequent washing of the precipitate, the yellow coloration faded away almost entirely, what remained being only a very pale yellowish tone of white.

The washed and dried precipitate

After washing and drying, I grounded the precipitate into a very fine powder. Looking under a microscope to the crystals of the compound I found out that they are long, thin and tend to stick together in the form of a stack.
The crystals of the compound viewed in blue light under an optic microscope

Another image of the crystals





In the end, I would like to add a few more images of the compound:

3 comments:

  1. NMR to confirm?

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  2. Unfortunately not. I didn't have acces to that although I would have wanted to undergo some tests in that direction so as to more precisely determine its structure.

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  3. Maybe its hydrophobic interactions and resultant coagulation that's all. As I expect a different color of a condensation product.

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