Lab 3 Williamson Ether Synthesis

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 Figure 3: IR for 4-bromophenol Discussion: After analyzing the HMNR and IR spectra of the final product, it was determined that the final product is 1-bromo-4-butoxybenzene which is derived from the unknown alkyl bromide 21KTF63XZ known as 1-bromobutane. O Br Br 1-bromobutane 1-bromo-4-butoxybenzene In the HNMR spectra for the product from unknown 21KTF63XZ, 13 hydrogens are represented. The peak just below 1.0 cm −1 can faintly be made out as a triplet, indicating that it has 2 hydrogen neighbors. This peak represents the 3 hydrogens of the CH 3 of the butane group. The peaks around 1.0 cm −1 with the integration value of 4 represents the 4 CH 2 hydrogens of the butane group. This peak is a multiplet due to the close proximity and the similar characteristic of the 4 hydrogens it represents. The hydrogens of the CH 2 directly adjacent to the oxygen is represented by the peak around 3.75 cm −1 which is a triplet. The triplet indicates that the hydrogen is being split by the two adjacent hydrogens on the alkyl chain. The two peaks from 6.5 cm −1 to 7.5 cm −1 , each with integration values of 2, represent the 4 hydrogens of the benzene ring. Each of them are doublets, meaning each of the hydrogens is being split by one neighboring hydrogen. By the HNMR spectrum, we know that there is no remaining starting material due to the high peaks and lack of DCM peak. This HNMR shows the product produced from the beginning alkyl bromide 4-bromophenol. Comparing the IR of the product to the IR of the starting material, it is evident that there is no starting material leftover in the final product. In the IR of 4-bromophenol, there is a broad peak from 3100 cm −1 -3400 cm −1 , indicating the presence of an alcohol. The IR of the final product lacks this, indicating the purity of the product. The peak on the product IR around 3000 cm −1 indicates aryl C-H bonds, and the peaks just under 3000 cm −1 indicate alkyl C-H bonds. Aromatic overtones are present in the 1700 cm −1 2000 cm −1 range which are further confirmed by the arene-indicating peaks around 1600 cm −1 . The IR spectrum confirms the purity and identity of the product. The percent yield was calculated to be 53.76%. This indicates that some of the product was lost during the experiment. This could have been due to the loss during extraction of the product with the separatory funnel. However, the final product was able to be isolated and identified as 1-bromo-4-butoxybenzene which means the starting unknown alkyl bromide is 1-bromobutane. Post-Lab Questions 1. OH O O O H O Cl O Cl OH NaOH H Cl O O O O OH O 2. A phase transfer catalyst allows reagents in the aqueous and organic layers to interact with each other by holding the two in close enough proximity that they are able to collide and interact. In this experiment, the phase transfer catalyst was TBAB, and it allowed the water soluble 4-bromophenol to react with the alkyl bromide. 3. If 1-(2-bromoethyl)-3-methylbenzene and phenol were used as the reactants in this experiment, 1-methyl-3-(2-phenoxyethyl)benzene would form as the product. 4.