Chemistry 350 Laboratory - Summer 2012                                               Professor T. Nalli, Winona State University

Expt #2. S_N2 Synthesis of an Aromatic Ether

Relevant textbook readings – Mohrig, Chapter 6-7, 10, 15. Klein, Chapter 7

References - (1) Experiment adapted from Esteb, J. J.; Magers, J. R.; McNulty, L.; Morgan, P.; Wilson, A. M J. Chem. Educ.2009, 86, 850. (2) Also see Wenkert, E.;  Youssefyeh, R. D.; Lewis, R. G. J. Am. Chem. Soc. 1960, 82, 4675.  

Overview – The S_N2 reaction is a versatile and stereospecific reaction that can be used for the preparation of a multitude of functional group families. These facts contribute to its great importance as a method for organic synthesis. The reaction generally involves a nucleophile attacking the electrophilic carbon of an unhindered alkyl halide (or alkyl sulfonate) displacing the halide (or sulfonate) leaving group.

In the reaction that you will be carrying out, the nucleophile is the naphthoxide ion formed from the reaction of  2-naphthol with sodium hydroxide.  The alkyl halide is 1-iodobutane and the expected product is butyl naphthyl ether (eq 1).

(1)

Procedures

Running the reaction.

To a 100-mL round bottom flask (rbf), add 0.56 g of NaOH and 1.0 g of 2-naphthol. Add 20 mL ethanol and a few boiling chips to the flask. Reflux the solution for 15 minutes or until all of the solids have dissolved. After 15 minutes add 1.0 mL 1-iodobutane by Pasteur pipet through the top of the condenser and then reflux for 1 h.

Work-up procedures.

Cool the reaction mixture on a cold water bath for 5 min. Slowly pour the solution over 25 g ice in a 250-mL beaker. Rinse the rbf with 25 mL ice-cold water and add this to the beaker. Swirl or stir the contents of the beaker until all of the ice has melted. Collect the solid product by vacuum filtration. Wash the product with a few mL of ice-cold water and then dry it somewhat by allowing air to flow through the solid for 5-10 min.

Characterization of Product

Obtain the melting point. (Use the references list to find a literature value.)

Obtain the ¹H NMR spectrum.

Obtain the IR spectrum using the thin film method; Dissolve 5 mg of the product in 5 drops of dichloromethane (DCM) in a small test tube place the solution on a salt plate and allow the DCM to evaporate as you let the solution spread out on the plate. The goal is a thin film of solid left evenly distribute on the plate. Place this single plate in the IR and obtain the spectrum.

Prepare a sample for GC-MS analysis. Dilute a few drops of your NMR sample in 10 mL DCM in a clean labeled vial.

Report - A full report is required for this lab.

Please try to integrate the answers to the assigned questions into your results and conclusions section for this report (rather than answering each sequentially).

¹H NMR - Be careful to first identify and label solvent peaks including CHCl₃ and water (usually at 1.55 ppm in CDCl₃ solvent.) Integrate all peaks and normalize so that the integrations directly show the number of hydrogens for each resonance. Several protons' resonances overlap to form messy multiplets.

Assigned Questions:

1.         Ethanol is not usually a solvent used for S_N2 reactions. Why not?  Can you predict an undesirable side reaction that might occur using the ethanol as a solvent that would not occur if we used THF as a solvent?

2.         Why is it important to mix the naphthol with sodium hydroxide before adding the electrophile?

3.         Why is it important to fully cool the product in an ice bath prior to vacuum filtration?  Why do you need to rinse your product with ice water instead of room temperature water?