Lab 12: Williamson Ether

What is the mechanism of the reaction? What kind of substitution is it?

Two mechanistic step for the Williamson ether synthesis

SN2 Substitution

Summary

• base catalyzed formation of the metal alkoxide/phenoxide

• Nucleophilic substitution to form the ether

Detailed

• Start with 4-bromophenol

• Tetrabutylammonium bromide will be the phase transfer catalyst (PTC); this is necessary to allow for the interaction of water soluble phenoxide and water insoluble alkyl halide at the interface of the two phases

What geometry must the alkoxide and alkyl halides be in for this reaction to occur?

The alkoxides and alkyl halides used for this reaction must
be 1º or 2º

If it is 3º, alkoxides/halides will result in elimination rather than
substitution

What does the microwave do?

allows the reflux period to shorten from 30 mins to 60 mins

What is the difference between extraction and washing?

Extraction: product will dissolve in the newly added solvent while impurities will stay in the original solvent (product into new)

Washing: impurities go in newly added solvent and the product will stay in the original (getting rid of impurities_

What is the protonated product soluble in? What about the deprotonated product?

Protonated

-insoluble in water

soluble in ether

Deprotonated

-soluble in water

-insoluble in ether

What does the column do?

Purify your product (column chromatography)

What is the purpose of this experiment?

We are going to generate a stable, Williamson ether product from a base catalyzed reaction between 4-bromophenol and an unknown alkyl halide

Then, we will use FTIR and HNMR for identification purposes

Balanced equation

See photo

Describe the extraction procedure

Solution from microwave vessel (add 10 mL of DI water and 10 mL of ether)

Separate organic from aqueous

Take aqueous and add ether

Combine the two organic layers

Add KOH to organic layer

Take the organic layer and wash two more times (this is when we will have the product in the original solvent and impurities in new solvent)

General procedure

Microwave

• Take TA prepared solution and add to Teflon microwave vessel

• Add TBAB and your unknown

• Perform microwave procedure for 30 mins

Extraction (this is when our product will be in the new solvent and impurities in the old solvent)

• Add mixture to separatory funnel

• add DI water and diethyl ether and mix

• separate organic and aqueous layer

• return aqueous layer to separatory funnel and extract with diethyl ether

• combine the organic layers

• wash the organic layer three times with KOH (aka you will get aqueous layer out and organic layer will still be left; then add more KOH to that left organic layer)

• draw organic (ether) layer with KOH

Column Chromatography

• column will be prepared by TA

• make sure column in packed (aka add steady amount of methylene chloride) and that methylene chloride is passing through column (we do not want it to become dry=level of the liquid must never be lower than the layer of sand at the top)

• add product to column with a pipette

• then add more methylene chloride to make sure all product is collected

Solvent Removal and Thin Layer Chromatography

• boil off solvent (do not evaporate product)

• other partner spot 4-bromophenol dissolved in methylene chloride and your alkyl bromide onto a TLC plate, leaving room for a third spot for your purified product

• once solvent has been removed, spot your purified product (helps see if your reaction went to completion because you have your product on one spot and reactant at the other spot)

Experimental techniques used

Thin layer chromatography

Column chromatography

Liquid-liquid extraction

Reflux

IR Spec

NMR Spec

Glassware used

separatory funnel and beaker

Table of reagents

• 4 bromophenol

• potassium hydroxide

• 1-bromopentane

• 1-bromo-3-methylbutane

• 1-bromobutane

• Tetrabutylammonium Bromide

• diethyl ether

• methylene chloride

• water

• sodium sulfate

Possible unknowns

see photo