Electrophilic Aromatic Substitution: Synthesis of Bisphenol Z

 Electrophilic Aromatic Substitution: Synthesis of Bisphenol Z

Abstract:

In this experiment students performed a synthesis of Bisphenol Z, from a reaction between phenol and cyclohexane with hydrochloric acid acting as the catalyst.  This synthesis was an example of an electrophilic aromatic substitution (EAS) reaction.  The students explored the nature and strength of the recrystallized pure Bisphenol Z product through thin layer chromatography (TLC), melting point (mp), and nuclear magnetic resonance (NMR).  The melting point of Bisphenol Z was 185oC - 190oC.  The IR showed a peak at 1717 from the ketone which means that it isn’t present in the product.  The students’ reaction produced a percent yield of 39.55%.  The expected percent yield was around 45%, because of the percent yield the students obtained, this experiment was not considered successful. The synthesis of Bisphenol Z was successful in this experiment.

Introduction:

In this reaction when the ketone is protonated with a proton source and the alcohol is protonated with a proton source two different electrophilic substitutions take place.  The alcohol in the reaction is an ortho/para donator, and the two phenols in the reaction are linked by a hydrocarbon.  The purpose behind this experiment was for students to successfully synthesize Bisphenol Z.  The large family of Bisphenol compounds are important in many major industries and the cause for much debate around health and environmental concerns.  According to an article titled “Structural and mechanistic insights into Bisphenols action provide guidelines for risk assessment and discovery of Bisphenol A substitutes,” Bisphenols are used in the production of different plastics, food can linings, electronic materials, thermal paper, and dentistry products.  According to the same article “studies have shown that BPA is released from consumer products, leading to its detection in food, drinking water, wastewater, air and dust...it has been hypothesized that early exposure to BPA could also play a role in the onset of obesity and other metabolic syndromes” (Delfosse, 14930).  It is important for students to understand how bisphenols are created if they have such a large impact on human health and the environment.  The experimental hypothesis was that the reaction between phenol and cyclohexanone while using Hydrochloric acid (HCL) as the catalyst, would synthesize Bisphenol Z.  The students performed the reaction by using reflux when phenol, cyclohexanone, HCL and water were heated and stirred for an hour.  The students then cooled the reaction, filtered it, recrystallized, filtered a second time to obtain the recrystallized Bisphenol Z.  The students then finished the reaction through determining the melting-point, doing a thin-layer chromatography and an NMR.  

Reaction Section:

Reaction:

[pic 1]

Mechanism:

[pic 2]

1. The solvent for this reaction is water.
2. Four possible equivalents of phenol were used because the bisphenol family forms 1:1 ratios with phenol, which means that there will be extra phenol in the reaction which allows for a more quantitative yield.
3. The mix of phenol and the bisphenol product is the adduct formed in this reaction.  To get rid of the phenol in the adduct, it is washed with hot water. After it is washed with hot water the crude mixture remained.
4. The adduct is being held together by hydrogen bonding between the phenol and Bisphenol Z molecules.  In the drawings below the hydrogen bonding is represented by the curved lines. The first drawing below represents a hydrogen bond between two different phenol molecules and the second represents the hydrogen bonding between Bisphenol Z and two different phenol molecules.

[pic 3]

1. This reaction is an electrophilic aromatic substitution.  The molecules in the reaction are achiral because there is no stereochemistry.
2. The nucleophile is the hydrogen on phenol, the electrophile is cyclohexanone, and the catalyst is HCL.  The hydrogen on the phenol is the nucleophile because it donates and electron pair to the cyclohexanone from protonation.  The OH+ on the cyclohexanone is the electrophile leaving the H+ from HCL as the catalyst.  The H+ will protonate the oxygen in the cyclohexanone to start the reaction.
3. Bisphenol A is a possible side product for the synthesis of Bisphenol Z.  Bisphenol A and Bisphenol Z are essentially the same reaction but Bisphenol A occurs when a Bisphenol Z reaction has not been fully completed.
4. Recrystallization was used as a way to purify the Bisphenol Z sample that the students obtained.  Recrystallization was used to take out the phenol that was present in the sample the students collected.  To recrystallize the sample students dissolved the Bisphenol Z in hot methanol and then cooled the solution in an ice bath.  Once the solution cooled students filtered the solution, while filtering the remaining product was washed with cold methanol and then dried until the next week.  The process of recrystallization uses hot methanol to dissolve pure Bisphenol Z and phenol and then it is cooled to reduce the solubility of the Bisphenol Z which then recrystallizes (Recrystallization Technique).
5. Meta is associated with withdrawing groups and ortho and para are associated with donating groups.The benzene ring and the OH group are both electron donors which explains why the lone pairs of the phenol lead to alkylation at the para position instead of meta or ortho.  
6. Adding a second phenol to the benzylic position of the molecule would take place via SN1 because it would need two steps.  In this SN1 reaction a catalyst and heat would be used to complete the reaction.  An SN2 reaction would occur when only one step was needed.

Experimental Section:

Students prepared a water bath of 100mL or water in a 250mL beaker on a hotplate and heated the water to around 70 °C.  They then added 3.83g phenol, 1g of cyclohexanone, and 1.7 mL of concentrated HCl to a 25 mL round-bottomed flask (RBF) with a small magnetic stirrer.  When everything was added two distinct layers formed, a cloudy white bottom layer and a pale yellow top layer. Attached a reflux condenser to the RBF which sat in the beaker with the bottom layer submerged in the water.  Performed the reaction for around an hour. The color changed from a pale yellow to a dark orange/red color.  Cooled the reaction in an ice bath and used a 25 mL side-arm flask to filter the product. Then students washed with about 30 mL of water followed with about 10 mL methanol, until the color changed to white. After drying the filtered product, students weighed the product, and kept samples for the following week . Then the product was mixed with boiling water, and then filtered the product again to remove the phenol. The solid was then washed with water, then dried, then weighed the final Bisphenol Z product. The Bisphenol Z was recrystallized using ice cold methanol and an ice bath.  Once the product was recrystallized it was filtered another time and put on a watch glass to dry for the next week.