Williamson Ether Synthesis Lab 3

Williamson Ether Synthesis Introduction: The purpose of this experiment is to perform the Williamson ether synthesis with 4bromophenol and an unknown primary alkyl halide. The unknown primary alkyl halide will later be identified using HNMR and FTIR spectrums after the final product is produced. The primary alkyl halide will be one of three things: 1-bromopentane, 1-bromo-3-methylbutane, or 1bromobutane. The unknown primary alkyl halide will serve as the electrophile in the SN2 reaction with 4-bromophenol. Potassium hydroxide serves as the nucleophile, deprotonating the 4-bromophenol as well as washing the solution. Tetrabutylammonium bromide (TBAB) is the solvent in which the reaction is carried out. Water and diethyl ether are used in extraction of the product. Methylene chloride is used to purify the product in column chromatography and also serves as the solvent in TLC. Sodium sulfate is used to dry the product. Microwave reflux, liquid-liquid extraction, column chromatography, TLC, FTIR spectroscopy, and HNMR will be utilized to conduct this experiment. Balanced Equation: Reaction Mechanism: Table of Reagents: Structure Information MW: 173.01 g/mol MP: 66.4°C Density:1.84 g/mL MW: 56.105 g/mol MP: 380°C Density: 2.04 g/mL MW: 151.05 g/mol MP: -95°C Density: 1.218 g/mL MW: 151.05 g/mol MP: -112°C Density: 1.261 g/mL MW: 137.02 g/mol MP: -112°C Density: 1.268 g/mL MW: 322.37 g/mol MP: 102-106°C Density: 1.039 g/mL MW: 74.12 g/mol BP: 34.6°C Density: 0.713 g/mL MW: 84.927 g/mol BP: 40°C Density: 1.33 g/mL MW: 18.02 g/mol BP: 100°C Density: 1.00 g/mL MW: 142.04 g/mol Safety:  Safety glasses, lab gloves and lab coats must be worn at all times.  Make sure to use snorkels when necessary and avoid spark, flames, hot surfaces, and vapors.  Make sure to dispose liquid waste in appropriate bottle in the hood.  If you are exposed to any of the below substances, report it immediately to your TA.  4-bromophenol can cause skin and eye irritation; ingestion or inhalation can cause irritation to respiratory tract.  Potassium Hydroxide can cause skin and eye irritation and erosion and lead to blindness and corneal damage; over-exposure can lead to lung damage.  1-bromopentane, 1-bromo-3methylbutane, and 1-bromobutane are highly flammable, can irritate skin, eyes, and respiratory tract.  Tetrabutylammonium bromide is hazardous if ingested or inhaled and can cause skin and eye irritation.  Diethyl ether is flammable; can irritate skin and eyes; mutagenic to mammalian somatic cells.  Methylene Chloride has carcinogenic effects; can irritate skin and eyes.  Sodium sulfate can irritate skin and eyes; can cause mild irritation if ingested or inhaled. Experimental Procedure: Preparation of Conjugate Base of 4-Bromophenol: A TA Demonstration: 1. The TA will prepare the conjugate base of 4-bromophenol prior to gathering of chemical. Microwave-Promoted Williamson Ether Synthesis: 1. Collect 8mL of the solution prepared by TA and place it into the white Teflon microwave vessel. 2. 2.90 g of tetrabutylammonium bromide is added followed by 3.02g of the unknown alkyl halide assigned by the TA all into the microwave vessel. 3. Stir bar is added to mixture then is returned to the TA. 4. The TA slides the vessel into its outer sleeve and caps the assembly. Use microwave procedure to execute reflux to the solution. 5. Allow reflux to cool, then TA will remove assembled vessel from microwave and open them inside fume hood and return white Teflon vessel back to you. Extraction: 1. Stir bar is removed from vessel then pour solution from microwave vessel into separatory funnel. 2. 10 mL of distilled water and 10 mL of diethyl ether is added to the separatory funnel, mix well. 3. Resulting layers are separated into two clean, labeled beakers. Aqueous layer is returned to separatory funnel and extracted with 10 mL diethyl ether. Those resulting layers are separated into to labeled beakers. 4. Combine the two organic layer then wash ether layer three times with 12 mL of 5% KOH, setting aside aqueous layer after each awash. Dry ether layer with sodium sulfate. Colum Chromatography: 1. Purify final product using column prepared by TA. Secure column with clamp. Prior to adding the mixture, pack column by adding steady amount of methylene chloride through top using a pipette. Don’t allow column to become dry. 2. When product is ready to be purified, add product mixture into column using a clean pipette. Once all product is added to column, ad 5-10 mL of methylene chloride to the column behind product mixture ensuring all product is collected. 3. Return column to TA and transfer purified product to clean, pre-weighed beaker. Solvent Removal and Thin Layer Chromatography: 1. Position snorkel carefully over pre-weighed beaker containing purified product. Boil off solvent at ~ 40C. 2. While one partner watches the removal, the other should spot 4-bromophenol dissolved in methylene chloride and your alkyl bromide onto TLC plate leaving room for third spot of final purified product. 3. Once most of the solvent is removed, spot TLC plate with spot of dilute purified product and run plate in methylene chloride. Continue solvent removal until ether and methylene chloride re removes. Collect mass of final product. Spectral Analysis: 1. Collect H NMR spectrum of sample with TA assistance. Also Collect FTIR spectrum of final product. In-Lab: Williamson Ether Synthesis Data:  Starting weight of 4-bromophenol: 3.46g  Starting weight of alkyl bromide: 3.033g  Starting weight of 25% potassium hydroxide: 7.12g  Starting weight of TBAB: 2.949g  Reflux time: 30 minutes  Volume of water added before wash: 10mL  Volume of diethyl ether used to rinse spin vane: 10mL  Volume of diethyl ether extractions: 20mL  Volume of 5% KOH washes: 45mL  Total volume of methylene chloride used for column: 8mL  Weight of recovered product: 2.462g  Unknown Alkyl Bromide Code: 21KTF63XZ Observations:  4-bromophenol resembled light pink crystals and gave off a strong odor.  The starting alkyl halide was a clear solution.  During extraction with diethyl ether, the organic layer had a cloudy appearance while the aqueous layer was clear.  Beaker weight = 98.075g  Beaker + Product weight = 100.537g  100.537g – 98.075g = 2.462g of recovered product Post-Lab: Williamson Ether Synthesis Results: Limiting Reagent Calculations: 3.46g 4-bromophenol X    .  .     3.033g 1-bromobuatne X X    X       = 5.07g 1-bromo-4-butoxybenzene *4-bromophenol is the limiting reagent* Percent Yield Calculations: .  .  X = 4.58g 1-bromo-4-butoxybenzene .  .           X 100 = 53.76% Figure 1: HNMR for the product from Unknown 21KTF63XZ X Figure 2: IR for the product from Unknown 21KTF63XZ