Experiment A Simple SAR study using Chemiluminescent Esters

The purpose of this experiment is to create several esters and perform a simple SAR study on the diesters formed and use the process of chemiluminescence which is the emission of light from a chemical reaction. This involves a molecule being generated in an electronically excited state and emitting a photon of light once it descends to the ground state. This experiment is a common practice with pharmaceutical companies when attempting to figure out what causes a pharmacophore to be best suited to target a specific protein or what changes are needed for a privileged structure to improve its activity and selectivity.

The compound that was chosen for this experiment was 4-nitrophenol. 4mL of 4-nitrophenol was placed into a round bottom flask and a stir bar. The importance of phenols is their reactivity with oxalyl chloride. The functional groups attached to the phenols is what changes reactivity with oxalyl chloride. This is due to the functional groups pulling electron density from the OH and making it easier to have the hydrogen pulled off of the oxygen after reacting with oxalyl chloride. 0.35 mL of trimethylamine was added to quench the mixture, then placed in an ice bath while being stirred. 1.2 mL of oxalyl chloride was slowly added, followed by a drop of trimethylamine. A drying tube was added afterwards and stirred at room temperature for 25 minutes. After stirring a pale yellow solution was formed. Upon filtering, the solid diester was dried.

Two small glass vials were then obtained and one vial had 3% hydrogen peroxide in acetonitrile while the second had 9,10-diphenylanthracene. A little bit of diester product was added to the 9,10-diphenylanthracene. After the diester was dissolved it was mixed with the hydrogen peroxide in the darkened fume hood and emitted a flash of blue light and disappeared shortly. This blue color is probably a result of 9,10-diphenylanthracene already emitting a deep blue color.

The light being emitted is due to the oxalate being oxidized from the hydrogen peroxide. This causes a high energy molecule to form which decomposes to CO2 gas and will then emit a photon. The photon is then absorbed by the dye (9,10-diphenylanthracene) resulting in an excited electronic state. Once the dye returns to the ground state, it will then emit a visible light.

In a chemiluminescent reaction there needs to be a reactant with conjugated double bonds that have either oxygen, nitrogen, or any hetero atoms. The second reactant needed will oxidize the first reactant which was hydrogen peroxide in this lab. Its electronic features mostly comprise of the conjugated double bonds going through several transitions of πà π* and nàπ*. Using these prerequisites, a good chemiluminescent reaction would involve luminol and hydrogen peroxide because the luminol has nitrogens as the hetero atoms and conjugated double bonds.

The reactivity of othro-vanillin is due to its acidity with a pka of 7.4 while phenol has a pka of 10. Because of acidity in basic conditions othro-vanillin is less reactive than phenol. Specifically, othro-vanillin’s conjugate base is weaker and as a result will be more stable. The stability is from the oxygen’s negative charge being resonance stabilized by the –CHO. This causes the conjugate base to be less nucleophilic compared to phenol’s conjugate base and thus being less reactive.

This study successfully produced chemiluminescent product by generating a molecule in an electronically excited state and emitting a photon of light once it descends to the ground state. This chemical reaction produced a flash of blue light due to oxalate being oxidized from the hydrogen peroxide resulting in an excited electronic state emitting a visible light once the dye utilized returned to a ground state. A problem that could have occurred when synthesizing a chemiluminescent product is not using an oxidizing reactant such as hydrogen peroxide since it a key figure in this type of reaction.