/n Bristol Community college Organic Chemistry II (CHM236) Prof. Raid Albattah Experiment 3: Williamson Ether Synthesis Purpose: The main purpose of this experiment is to produce methylphenoxyacetic acid by SN2 reaction using Williamson ether synthesis. Materials: KOH, cresol, chloroacetic acid, Conc. HCl, 250mL bottom flask, hot plate, pH paper, Filter paper, condenser, ice bath, and Buchner funnel Introduction: The scientist who developed this reaction, Alexander W. Williamson, was a professor at University College in London in the latter part of the 1800's. The Williamson ether synthesis is the most widely used method for ethers synthesis. The mechanism involves an Sò2 reaction in which a metal alkoxide (nucleophile) displaces the halide ion from an alkyl halide. The alkoxide ion is prepared by the reaction of an alcohol with a strong base such as sodium hydride. Since this is SN2 reaction, thus primary alkyl halide produces high yield while secondary alkyl halide and sulfonate esters are occasionally used but the yields are often poor. See this link for the reaction mechanism https://www.youtube.com/watch?v=NqdMwMqGwvQ The ether prepared in this experiment is methylphenoxyacetic acid, a phenolic ether that is prepared from a methylphenol (cresol) and chloroacetic acid. Methylphenoxyacetic acid family used as herbicides especially 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5- trichlorophenoxyacetic acid (2,4,5-T). H3C p-cresol OH 1) H₂O, KOH OH 2) H₂O, HCI + HCl H3C p-methylphenoxyacetic acid chloroacetic acid OH Bristol Community college Organic Chemistry II (CHM236) Prof. Raid Albattah Experiment 3: Williamson Ether Synthesis Procedure: 1) Dissolve 4 g of KOH in 8 mL of water in a 250mL round bottom flask. Add 3 boiling stones. 2) Add 2 grams of your mystery cresol (x, y, or z) to the round bottom flask in the hood. Swirl until homogenization. 3) Fit the flask with a reflux condenser and heat to a gentle boil (fig 1). 4) Add 6 mL of a 50% aqueous solution (g/mL) of chloroacetic acid dropwise through the condenser to the boiling solution over a period of 10 minutes. 5) Boil for another 7 minutes. 6) Transfer the solution to a small beaker and cool it to room temperature. 7) Acidify the solution by dropwise addition of Conc. HCl. Monitor the pH with pH paper. 8) Cool the mixture in an ice bath until precipitate formation. 9) Filter the precipitate by vacuum filtration (be aware to weigh the filter paper before filtration). 10) Allow the solid to air dry in your laboratory drawer. 11) Weigh the solid and obtain the melting point during the next week's laboratory period. 12) Hand in a properly labeled sample of your product. Include your name, melting point of product, name of product. Disposal: Liquids in liquid disposal. Solids in solid disposal. Bristol Community college Prof. Raid Organic Chemistry II (CHM236) Albattah Experiment 3: Williamson Ether Synthesis Question Calculations. 1) Calculate the number of moles in 4 grams of KOH. 4g/(56.11g/mol) = 0.07moles 2) Calculate the number of moles in 2 grams of cresol. 2g/(108.14g/mol) = 0.018moles 3) Calculate the number of moles in 3 grams of chloroacetic acid. 3g/(94.5g/mol)=0.032moles 4) Calculate the maximum yield of methylphenoxyacetic acid than can be obtained in this experiment (i.e. calculate the theoretical yield). 0.018mol*166.17g/mol=3.07g 5) Explain why phenols would be acidic and why it easily reacts with base. Phenols are acidic due to the presence of a hydroxyl group (-OH) attached directly to an aromatic ring. The oxygen atom in the hydroxyl group can donate a proton (H+) to a base, making phenols acidic. Phenols easily react with bases because the base can accept the proton from the hydroxyl group, forming a phenoxide ion. Phenols easily react with bases because the base can accept the proton from the hydroxyl group, forming a phenoxide ion. 6) Why does the ether precipitate when the alcoholic reaction mixture is poured into water? The precipitation of the ether when the alcoholic reaction mixture is poured into water occurs due to the difference in solubility between the two liquids. Ether is less soluble in water compared to alcohol. When the reaction mixture is added to water, the alcohol dissolves in water, while the ether, being less soluble, forms a separate layer or precipitates out. Bristol Community college Organic Chemistry II (CHM236) Prof. Raid Albattah Experiment 3: Williamson Ether Synthesis 7) Why does cresol react with chloroacetic acid even though cresol is practically insoluble in water? Cresol can still react with chloroacetic acid even though it is insoluble in water because the reaction takes place at the interface between two phases. 8) Why do you think secondary haloalkanes such as 3-chloropentane give poor yields with this method? Because they undergo an elimination reaction rather than a substitution reaction.