Week+6-+Electrophilic+Aromatic+Substitution+(EAS)+Reactions

=Week 6- Electrophilic Aromatic Substitution (EAS) Reactions=

**Iodination of vanillin (4-hydroxy-3-methoxybenzaldehyde) to 5-iodovanillin (4-hydroxy-5-iodo-3-methoxybenzaldehyde)**
=Introduction:=

Substitution of alkyl compounds are typically nucleophilic substitution processes. In aromatic substitutions, however, the compounds most often undergo electrophilic substitution. In general, this process is a two-step addition-elimination mechanism where the electrons involved in the pi bonds of the aromatic ring attach the electrophilic reagent, forming a carbocation intermediate. Then the leaving group (very often just a proton) is eliminated, to form the product. For example:

The purpose of this lab is to synthesize 5-iodovanillin (4-hydroxy-5-iodo--3-methoxybenzaldehyde) from vanillin (4-hydroxy-3-methoxybenzaldehyde). The reaction is described below in Picture 2.


 * Vanillin** (4-Hydroxy-3-methoxybenzaldehyde) is a phenolic aldehyde, an organic compound with the molecular formula C8H8O3. Its functional groups include aldehyde, ether, and phenol. It is the primary component of the extract of the vanilla bean. Synthetic vanillin, instead of natural vanilla extract, is sometimes used as a flavoring agent in foods, beverages, and pharmaceuticals.



=**Procedure:**=

1. In a 100mL round-bottom flask, with a magnetic stir bar, dissolve 1.0 g vanillin in 20 mL of ethanol. Add 1.17 g sodium iodide and cool in an ice bath to 0 C. 2. Use a separatory funnel, add 11 mL aqueous hypochlorite solution dropwise over about 10 minutes. Color of solution should turn from pale yellow to reddish brown. 3. Allow mixture to warm to room temperature and continue stirring for 10 minutes. 4. Add 10 mL sodium thiosulphate solution then acidify solution (use pH paper to monitor pH) about 6 mL of HCl are solution are typically required. There should be a precipitate now (aryl iodide) 5. Remove the ethanol from solution using a rotary evaporator. This should take no more than 10 minutes with heating. (Picture 4) 6. Cool flask in an ice bath for 10 minutes, then collect the precipitate by vacuum filtration. Wash with cold water and then with cold ethanol. Continue to draw air through the mixture to dry as much as possible. Weigh the product. 7. Place product in 100 mL Erlenmeyer flask flask and while heating add enough 2-propanol to dissolve it. When mixture is clear, add hot water until the mixture appears cloudy. Then, add enough 2-propanol to get a clear (but colored) solution. Allow solution to cool at room temperature and then place in an ice bath to ensure as complete as possible crystallization (the slower the cooling, the bigger and better the crystals). 8. Collect the crystallized product by vacuum filtration, again allowing air flow for several minutes to facilitate drying. 9. Weigh final product and determine its melting point using MelTemp. Source: Doxsee, Kenneth M., and James E. Hutchison. //Green Organic Chemistry: Strategies, Tools, and Laboratory Experiments//. Southbank, Vic., Australia: Thomson-Brooks/Cole, 2004. 186-87. Print



Data/Analysis:
Reaction:
 * Contents added to the 100 mL round-bottom flask || Observations ||
 * 1.010 g of vanillin added to 20 mL of ethanol || Vanillin dissolved in the ethanol through stirring. The mixture turned cloudy. ||
 * 1.17 g of sodium iodide || Sodium Iodide is added to the mixture. The mixture turns a dark reddish brown color. It is stirred for 15 minutes in an ice bath. ||
 * 11 mL of aqueous sodium hypochlorite solution || Is added dropwise through the separatory funnel for 11 minutes. (roughly a drop every 3 seconds) The mixture slowly turned to a pale yellow. It is then allowed to warm to room temperature while stirring continued. ||
 * Decision to add approximately one drop every three seconds was based loosely on Pasteur pipettes dosage of 20 drops/mL. Also, the separatory funnel's drop rate was difficult to regulate and uneven at times, so the 1 drop / 3 sec is an average/estimate.

Workup and Isolation: 10 mL of sodium thiosulfate solution is added to the mixture. To acidify the mixture, 3.1 mL of Hydrochloric acid is added. There is a visible precipitate which is aryl iodide. The ethanol is then removed from the suspension on a rotary evaporator. The flask is then cooled in an ice bath for 10 minutes. The precipitate is then collected through vacuum filtration (it is not rinsed with ice cold water or ethanol). The crude product obtained weighed 1.556 g. The crude product is then placed in a 100 mL Erlenmeyer flask and 60 mL 2-propanol is added to dissolve the product and generating a clear (but colored, miller lite color) solution while being heated. No water was added, the mixture was already cloudy. The flask is then cooled at room temperature, then placed in an ice bath to obtain maximum crystallization. Vacuum filtration is then used to collect the crystalline product and allowed to dry.

Characterization: 0.025 g of the final product is recovered. A small amount is then added to a capillary tube and put in a Mel-temp to obtain the melting point. The substance did not melt, it decomposed. At 175 ºC it began to change color and by 180 ºC it had turned a burnt red. curious! This is about what you would expect for the melting temp, but you would not expect the decomposition. Hmm!

Percent Yield Calculations: 1.010g C8H8O3 * (1 mol/ 152.704g) = 0.0066 mol

0.0066 C8H8O3 mol * (1mol C8H7O3I/ 1 mol C8H8O3) = 0.0066 mol C8H7O3I 0.0066 mol C8H7O3I * (278.596g/ 1 mol C8H7O3I) = 1.839g = 1.8g Theoretical Yield Actual Yield is 0.025g C8H7O3I

(0.025g C8H7O3I/ 1.8g C8H7O3I) * 100 = 1.3% Yield Calculation okay. Sorry about the low yield, that's a drag.

=**Conclusion:**= In this experiment, the iodination of vanillin was unsuccessful. The melting point was not obtained. Instead the substances decomposed close to the melting point temperature (183-185 ºC) of the desired product. The substance reacted with the heat creating a new compound. This observation confirms that 5-iodovanillin was not the final product, containing impurities. Errors that may have caused the impurity and low percentage yield may have been the addition of bleach too quickly and some of the product may have been lost to and from the rotary evaporator. In step 7, where the crude product was heated while adding 2-propanol, the procedure called for the addition of water to make the liquid cloudy. The liquid was already cloudy so no water was adding which is another possible error. As mentioned earlier, the drop rate of the separatory funnel was very difficult to regulate, which could have had a negative effect on the outcome. =**Post Lab:**= Atom Economy illustrates the conversion efficiency of a chemical process in terms of desired products produced. Atom economy is written as (mass of atoms in desired product/ mass of atoms in reactants) * 100%:
 * Vanillin’s starting weight || 1.010g ||
 * Crude product weight || <span style="font-family: 'Arial','sans-serif'; font-size: 13px;">1.556g ||
 * <span style="font-family: 'Arial','sans-serif'; font-size: 13px;">Final product weight || <span style="font-family: 'Arial','sans-serif'; font-size: 13px;">0.025g ||
 * <span style="font-family: 'Arial','sans-serif'; font-size: 13px;">Melting point was not obtained. Literature value for 5-iodovanillin is reported as 183-185 ºC (Doxsee) ||

<span style="font-family: 'Arial','sans-serif'; font-size: 13px;">Product: 278.596g/mol C8H7O3I

<span style="font-family: 'Arial','sans-serif'; font-size: 13px;">Reactants: <span style="font-family: 'Arial','sans-serif'; font-size: 13px;">152.704g/mol C8H8O3 <span style="font-family: 'Arial','sans-serif'; font-size: 13px;">149.89g/mol NaI <span style="font-family: 'Arial','sans-serif'; font-size: 13px;">74.44g/mol NaClO <span style="font-family: 'Arial','sans-serif'; font-size: 13px;">Added together = 377.0

<span style="font-family: 'Arial','sans-serif'; font-size: 13px;">(278.596g/mol C8H7O3I) / (377.0g/mol reactants) * 100 = 73.90%

Works Cited:
<span style="color: black; font-family: 'Arial','sans-serif'; font-size: 13px;">Doxsee, Kenneth M., and James E. Hutchison. //Green Organic Chemistry: Strategies, Tools, and Laboratory Experiments//. Southbank, Vic., Australia: Thomson-Brooks/Cole, 2004. 186-87. Print

<span style="font-family: 'Arial','sans-serif'; font-size: 13px;">Higginbotham, Carol. Ph.D. “EAS Reaction.” CH-335: Organic Chemistry Course. COCC/UO: Blackboard, Winter 2012. Web. 23 Feb 2012

<span style="color: black; font-family: 'Arial','sans-serif'; font-size: 13px;">"Overview, Electrophilic Aromatic Iodination of 4'-Hydroxyacetophenone." //GEMs Home//. Web. 23 Feb. 2012. <http://greenchem.uoregon.edu/Pages/Overview.php?CategoryIDString=>.