Electrophilic+Aromatic+Iodination+of+Vanillin

**__ Introduction __**
The chemistry regarding aromatic compounds is important for their unusual stability through delocalization energy and their prevalence in nature. The aromatic benzene was first discovered by Michael Faraday as a residue from heating the city of London from whale oil (Bruice 624). These compounds were named as a result of the sweet fragrances the molecules produced. Vanillin is an aromatic compound with the molecular formula C8H8O3. Functional groups on the molecule include an aldehyde, ether and phenol. Acting as the primary component of the extract of the vanilla bean, it is also found in roasted coffee and the Chinese red pine.

In lab, vanillin reacted in situ with sodium iodide to form 5-Iodovanillin. By also taking a greener approach to chemistry, the use of household bleach (NaOCl) in lieu of nitric acid was used as a less hazardous oxidizing agent. Selective electrophilic aromatic substitutions such as this are common in synthesis to form larger aromatic pharmaceutical or biological compounds.

=﻿__Procedure__=

Procedure can be found at Gilbertson, R.; Parent, K. E.; McKenzie, L. C.; Hutchison, J. E. //Electrophilic Aromatic Iodination of 4'-Hydroxyacetophenone// Greener Approaches to Undergraduate Chemistry Experiments, Print Kirchhoff, M., Ryan, M., Eds.; American Chemical Society: Washington D.C., 2002; pp 1-3.

Revisions given in lab to above procedure include: use of vanillin not 4-hydroxyacetophenone, 11mL of bleach, adding the bleach over a 10 minute period not 30 minute, and letting the solution mix for 10 minutes instead of 1 hour. The recrystallization process from the above source was not followed. The process came from Doxsee, K. M.; Hutchison, J. E. //Green Organic Chemistry - Strategies, Tools, and Laboratory Experiments//, Print 2004; pp 186-187. Step number 7.

__ Reactants: __
NaI: Sodium iodide was off-white, yellow granular powder.

C8H8O3: Vanillin was a white filamentous crystalline substance. Smelled of cooking vanilla.

__ Process: __


0.998g vanillin (s) added to 20.0 mL ethanol in a 150mL round-bottom flask and aggregated until it dissolved completely.

To the same flask, 1.209g NaI was added and mixed. Which caused the liquid to change from clear and colorless to clear with a slightly yellow/orange hue.

The flask was then submerged in an ice bath and allowed to cool to 3°C. At this temperature, the bleach drip was started using the separation funnel.

As the first drops of the 11 mL of bleach in the separatory funnel were mixed with the solution. The color changed immediately to a rich brown/red indicating the oxidation of iodine was happening. The flow was adjusted to allow for one drop/3 seconds over a ten minute period and left alone until the contents of the separation funnel had all been transferred to the round bottom flask.

As the last few drops of bleach entered the flask, the color of the solution changed from dark brown to a very dark caramel color.

The solution remained in the ice bath for approximately five minutes. The ice bath was removed and the solution was allowed to rest for ten minutes to continue the substitution reaction.

70 drops of 10%HCl were added drop wise to the solution resulting in a pH of 5. Lowering the pH resulted in a phenol precipitate in the solution where there had previously been none. They were small clumps, with the apparent consistency of cottage cheese.

The contents of the flask were then added to the RotoVap and the ethanol was boiled off. During this step, some of the solid was lost during the transfer from one to another, and then back again. When the resultant product was put back into the round bottom flask, it was significantly less viscous. Deionized water added to the boiling flask to retrieve additional solid.

The round bottom flask and its contents were again submerged in an ice bath and allowed to cool.

Once cooled, the solution was vacuum filtered with a DI water wash. The liquid that was filtered out collected in the erlenmeyer flask was clear with a strong yellow hue. The solid left in the filtration pan was silky and creamy in appearance, with slightly yellow-eggshell coloration.

This solid was then added to a clean flask with 4mL of 2-propanol to completely dissolve. 4mL of warm H2O was added and the flask was aggregated. The solution changed from clear to opaque and cloudy.

12mL of 2-propanol were added drop wise until the solution lost all of its cloudy nature. The resulting solution separated into two layers: an off-white "fluffy" solid on the bottom, and a yellow/orange clear liquid on the top.

The flask was removed from the heat and allowed to cool slowly. Once the solution was only warm to the touch, it was again submerged in an ice bath.

The solution was once again vacuum filtered and the resulting crystals stored in a pre-weighed vial.

**__ Analysis __**

 * __ Purity Analysis: __**



__Product:__

 * 5-iodovanillin**

The solid formed off white pastel powdered crystals.

Weight of empty vial: 24.918g

Mass of product and vial: 25.872g

Product mass: 0.954g = actual yield.



__ Discussion/Conclusion __
During the second step of this reaction, while the carbocation intermediate is present, an elimination of a proton occurs according to the reaction presented in lab on the black board. While we "know" that this happens because professor Higginbotham says it does, one might wonder why a strong nucleophile doesn't attack the carbocation before the elimination of the proton can occur. There are two significant reasons: steric hindrance and resonance.

The carbocation drawn in lab rests on a secondary carbon. In reality, the + is not localized on that specific carbon; this molecule has numerous resonance structures. This resonance stability results in a molecule that isn't in a hurry to get rid of the + charge.

Steric hindrance is also a factor. The cyclohexane ring is already highly substituted with large substituent's. Of the six carbons, four of them are substituted with multiple atom groups, or very large single atoms like I. This is not as significant when one considers the resonance stability, but it could play a role in the exclusion of a nucleophillic substitution.

In the electrophilic aromatic substitution, sodium Iodide was oxidized to form an elecctrophile to attack the stable aromatic ring, The Iodine cation, acting as the electrophile, waits for the vanillin nucleophile to attack the cation. This results in the formation of a carbocation intermediate. The stable nature of the aromatic molecule results in a slow formation of the higher energy carbocation. The base in the reaction will then attack the proton at the electrophilic attack site to restore aromaticity. The final product of this electrophilic substitution was 5-iodovanillin.

Purity was assessed through melting point. Two capillary tubes were loaded and tested. The sharp melting point of 179.9-181.2°C was the first indication of purity. Comparing this melting point to literature values indeed indicates that pure product was formed from the reaction.

In the interest in improving the 52.4% yield, one error that may have occurred during the experiment was adding the bleach too quickly. The separatory funnel was opened too much initially and quite a bit of bleach went into the flask. The procedure states that the bleach needs to be added slowly over a ten-minute period in order to obtain the best results. Another possible error may have been not using deionized water in dissolving the crystals. Whoops! Anytime that water goes into a reaction flask or test tube, it needs to be deionized. This could have added any impurities found in the plumbing of the chemistry lab of COCC such as Cu. Lastly a possible error may have been not all of the substances making it into the round bottomed flask. Once the bleach was added the neck of the flask also turned a dark brown color. Nonetheless, a pure product and a moderate yield occurred in the electrophilic aromatic iodination of vanillin.

Calculate the __atom economy__ for this reaction. Atom economy is defined on Wikipedia, but essentially is the formula mass of the desired product divided by the formula mass of all reactants (don’t include catalysts or solvents in our reaction). Look again! http://en.wikipedia.org/wiki/Atom_economy Vanillin: .998g 5-iodovanillian: .954g Atom Economy = 0.954g/0.998g x 100 = 95.5% Nice report. Scores: format (2/2) style (2/2) data (3/3) quality of result (1/1) quality of reported data (1/1) conclusion (2/2) error (1/1) post-lab Q (0.5/2) for a total of 12.5/14.
 * __ Post-Lab Question: __**