CH 2020/2270/2290 Synthesis of n-Butyl from n-Butanol (An SN2 Reaction) (adapted from Organic Chemistry: A Short Course, H. Hart, L. E. Craine, D. J. Hart, and T.K. Vinod 13th ed. Houghton-Mifflin, Boston, 2012.) Reference: Bruice, P.Y., Seventh Edition, Chapter 9)

Materials From the Chemicals Hood: From the Stockroom (Blue Bin): n-butyl Small metal clamp bromide Concentrated sulfuric acid 100 mL round-bottom flask 5% aqueous solution (2) Wire clips Calcium chloride 15% in anhydrous Separatory funnel solution Cork ring with stopcock 2-bromobutane 1” stirbar tert-butyl bromide Stirbar retriever (2-bromo-2-methylpropane) Allyl bromide (3-bromopropene) Benzyl bromide Bromobenzene Glass stopper Brine Reflux condenser

In this experiment you will convert n-butanol to n-butyl bromide by reaction with sulfuric acid and sodium bromide. Primary alkyl can be prepared from the corresponding by treatment with sodium bromide and sulfuric acid. in generated in situ according to the equation

NaBr + H SO 2 4 HBr + NaHSO4

Excess sulfuric acid is used, and the mechanism involves the SN2 displacement of the protonated hydroxyl group (water) by bromide . Water is the leaving group.

CH3CH2CH2CH2 OH + H Br CH3CH2CH2CH2 OH + Br 2

slow, rate-determining step CH3CH2CH2CH2 OH2 + Br CH3CH2CH2CH2 Br -H2O

Procedure Place 13.6 g of sodium bromide, 12 mL of water and 8.0 g (10.0 mL) of n-butyl alcohol (also known as 1- butanol) in a 100-mL round-bottom flask. Add a magnetic stir bar and cool the mixture with stirring for 10-15 min in an ice-water bath. Add 15 mL (28 g) of concentrated sulfuric acid in 2-3 mL portions, thoroughly mixing and cooling after each addition. Attach a condenser to the flask and connect the condenser to the tap water (as depicted in Figure 1), heat the mixture to boiling (hot plate no hotter than 275 °C) and maintain reflux for 30 min. Lower the temperature if white fumes are visible out the top of the condenser.

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Figure 1: Reflux apparatus

Discontinue heating and cool the reaction mixture by immersing the flask in an ice-water bath. Pour the liquid reaction mixture through a funnel into a separatory funnel. If solid remains in the round-bottom flask, add 24 mL of water to dissolve the solids and transfer this solution into the separatory funnel. If no solids had precipitated, add the 24 mL of water straight into the separatory funnel with your reaction mixture.

Shake the separatory funnel well, and allow the layers to separate. Discard the aqueous layer into a 400- mL beaker and retain the organic layer. See Table 1. Wash the organic layer successively with 12-mL portions of concentrated sulfuric acid, water, 5% aqueous sodium hydroxide, and water again. Keep the concentrated sulfuric acid and aqueous sodium hydroxide washes in separate beakers. In each operation be sure that you keep the organic layer and do not accidentally throw away your product. DO NOT THROW AWAY ANY LAYERS UNTIL YOU HAVE COMPLETED THE ENTIRE EXPERIMENT. When your product is the bottom layer, you must drain it out into a clean beaker, drain out the wash layer, and then pour your product back into the separatory funnel to continue.

Alkyl bromides are usually more dense than water but less dense than concentrated sulfuric acid. See list on page 4.

Table 1: Aqueous washings of n-butyl bromide product Wash with: 1st water Conc. sulfuric acid 2nd water 5% NaOH (aq) 3rd water n-butyl bromide layer: Top* Top Bottom Bottom Bottom

(*This water wash layer may be more dense than n-butyl bromide because of salts dissolved in the water. To check whether the bottom layer is aqueous or organic, add 2-3 drops of the bottom layer to 2 mL of water in a test tube. If the 2-3 drops dissolve in the water, the bottom layer is aqueous. If the 2-3 drops sink to the bottom of the test tube, the top layer is aqueous, the bottom layer is n-butyl bromide, and in this case you will need to pour the contents of the test tube back into the separatory funnel.)

2 Transfer the crude product to a dry 50-mL Erlenmeyer flask containing enough anhydrous calcium chloride (CaCl2) to just cover the bottom of the flask. Swirl the mixture until the solution is clear (not cloudy). Gravity filter the liquid through a small (pea-sized) plug of cotton into a previously weighed vial. Reweigh the vial with the n-butyl bromide in it. You will test this product with sodium iodide along with the other organic halides provided in small bottles in the hood.

Waste Disposal Check the pH of the aqueous solutions in the beakers. If it is acidic, it must be poured into the Acid Waste container. If it is basic, it must be poured into the Base Waste container. The used calcium chloride should go into Inorganic Waste.

REACTIVITY OF HALIDES TOWARD SODIUM IODIDE In this part of the experiment, you will test the reactivity of several alkyl halides in an SN2 reaction. Iodide ion is an effective in SN2 displacements. In acetone solution, other alkyl halides can be converted to alkyl iodides.

acetone I + R X R I + X

Although we might expect such a reaction to be reversible, using anhydrous acetone as the solvent can drive it forward. Sodium iodide is soluble in this solvent, whereas and sodium bromide are not. If a reaction occurs, a precipitate of sodium chloride or sodium bromide forms.

The mechanism involves a one-step, concerted, SN2 displacement. Therefore, the reaction occurs most quickly when attack at the carbon that bears the (X) is least hindered sterically. For alkyl halides, the order of reactivity is primary > secondary > tertiary. This is the reverse of the order observed in the earlier SN1 experiment.

Procedure Use scrupulously dry test tubes for this part of the experiment. Do not wash with water.

To each of seven clean, dry test tubes, add 2 mL of a 15% solution of sodium iodide in anhydrous acetone. To one test tube, add 10 drops of the 1-bromobutane you just synthesized, swirl, and record the extent of sodium bromide precipitation that forms. Be descriptive in your observations. If there is no reaction after 5 min, write, “does not react” in your notebook.

Test each of the following organic bromides similarly: 2-bromobutane, t-butyl bromide, allyl bromide (3- bromopropene), benzyl bromide, and bromobenzene. Use the seventh test tube containing only the sodium iodide-acetone reagent as a comparison control. Examples of the six test tubes with reactions can be seen in Figure 1 below.

Caution Wear disposable gloves and avoid skin contact. Some compounds (benzyl bromide, allyl bromide) used in this experiment are lachrymators. Lachrymators cause eye irritation and produce tears. The test solutions that contain these compounds should be poured into the halogenated waste container, and the test tubes used for the reactions must be rinsed with acetone.

Waste Disposal Pour the contents of each test tube into the Halogenated Waste container.

3 Densities of Liquids n-butyl bromide 1.24 g/mL water 1 g/mL conc. H2SO4 1.84 g/mL 5% aqueous NaOH 1 g/mL

Figure 1. Test tubes with reaction products of organobromides with sodium iodide in dry acetone.

From left to right:

Br Br Br Br Br Br

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