Experiment 8

Objectives

You will perform a nucleophilic substitution reaction. This S_N2 reaction will use acidic conditions to make the alcohol into a more reactive chemical and use the Br^- ion as the substitution nucleophile. You will use a reflux to allow the reaction to proceed for a longer period of time, and then a simple distillation to collect the more volatile organic compound, 1-bromobutane. After collecting your product, you will perform a Separatory Funnel extraction to isolate your product. The 1-bromobutane will be further characterized during the next lab period by determining density, refractive index, yield and boiling point.

Background

This experiment is the second in which you will carry out a reaction with the specific purpose of making a new compound. Previously you produced and ester, but here you will convert an alcohol into an alkyl halide. It is your responsibility to read the procedure carefully before coming to lab and understand the laboratory techniques you will be using. When you understand the procedures, you will be more comfortable and proficient in the lab. Since you have done a reflux before, set that up using the 250-mL round bottom flask described. Be care to measure chemicals accurately and be careful since you will be using concentrated sulfuric acid which is extremely dangerous.

Nucleophilic substitutions are one of the most generally useful classes of synthetic organic reactions. This experiment introduces this class of reactions, specifically the 2nd order nucleophilic substitutions, or S_N2.

As you learned in lecture, this general class of reactions requires three things: a nucleophile, an electrophile, and a leaving group. In order for the reaction to proceed via the S_N2 mechanism, the nucleophile should be in the "good" to "excellent" range, the electrophile must be unhindered (methyl or 1°), and the leaving group should also be in the "good" to "excellent" range.

In applying these criteria to the transformation we wish to make here (in acid, water is the leaving group),

CH₃CH₂CH₂CH₂-OH₂⁺ + Br^- → CH₃CH₂CH₂CH₂-Br + H₂O

we see that the first two are satisfied (bromide is an excellent nucleophile and the electrophile is a 1° alkyl group), but hydroxide is a poor leaving group, due to its negative charge and its high basicity.

The central question becomes, "how can we make OH^- into a better leaving group? We have a few choices: 1) react the alcohol with p-toluenesulfonyl chloride (abbreviated TsCl), which will convert the —OH group into a sulfonic acid ester, making it a much better leaving group--then react the ester with sodium bromide to produce 1-bromobutane; 2) react the alcohol with phosphorus tribromide (PBr₃), which converts the —OH into a "—P(OH)X₂" leaving group (where X is either —Br or —OH), and which also produces free bromide ions which react with the electrophile, replacing the new leaving group, all in one reaction mixture; or 3) using a strong acid to protonate the —OH group in the presence of the bromide ion, which changes the leaving group from hydroxide to water, and allows the bromide to react with it in the same mixture. We will use the last of these methods.

Procedure

Safety: 1-butanol and 1-bromobutane are both flammable liquids and irritants-- no flames will be allowed, and wear gloves while handling them. Concentrated sulfuric acid is strongly corrosive and toxic--wear gloves while handling it, and be sure to wash your gloves and your hands immediately after handling it. Sodium bromide, sodium bisulfite and calcium chloride are all irritants--gloves are recommended.

Day 1

To set up your experiment, do the following.

1. Obtain a 250-mL round bottom flask from the upper cupboards near the stockroom or on the cart. Make certain your flask is clean and you have the appropriately sized ground glass stopper if you have a side arm in the flask.
2. Obtain a cork ring from one of the drawers to sit the round-bottom flask in while you add chemicals. Never let your flask rest in the heating mantel when not in use.
3. Prepare an ice-water bath in a 600 mL beaker, if your 250-mL flask fits inside the beaker, or use the ice bucket in the hood to place your flask in it to keep your flask cool when adding the concentrated acid.

After preparing your reaction flask as described above, do the following:

1. Add 20.0 g of sodium bromide to your 250-mL round bottom flask. 
2. Add 15.0 mL of DI water to the flask. Swirl the contents of your flask until most (but not all) of the sodium bromide is dissolved. (Some crystals will not dissolve until heated but everything will dissolve quickly when heated.)
3. Add 15.0 mL of 1-butanol to your reaction flask.
4. Place the flask, containing the above reaction mixture, in the ice-water bath or bucket (make sure the flask cannot tip over!!).
5. Slowly add 15 mL of concentrated sulfuric acid to the flask.  Add about 1 mL at time, letting the acid run down the inside wall of the flask (use the side arm if your flask has one). Swirl the contents after each incremental addition to cool the contents.
6. After all acid has been added, assemble the flask into a reflux setup with a condenser column attached to the flask (a drying tube is not used; don't forget to add a few boiling stones).
7. Reflux the mixture for 45 minutes, making sure the reflux vapor ring does not rise above the halfway point of the condenser.
8. When the reflux is over, turn off the heat and allow the condensate in the condenser to drain back into the flask.
9. After the reflux setup has cooled somewhat, use the reaction flask as the distillation pot for a simple distillation.
10. In the collection flask (50- or 100-mL round-bottom flask), add about 20 mL of water.
11. Heat reaction mixture and continue to collect the distillate that has a density greater than that of water. There is no need to monitor the temperature as both water and 1-bromobutane will be vaporized. You should monitor the distillate to observe whether there still a water-insoluble chemical being distilled (and collected) by observing whething the distillate is more dense than the water previously added to the collection flask. When there appears to be no more water insoluble droplets (with a density greater than water) coming across, turn off the heating mantel.

The distillate contains both water and 1-bromobutane with a little sulfuric acid mixed in. Purify your product as follows:

1. Using a separatory funnel, wash the distillate with about 20 mL of a 1.0 M NaCl solution.  (How do you know which layer contains your organic product? Is the organic layer always the top layer?). If any pink color (due to the presence of Br₂) forms during this process, add about 0.1 g of sodium bisulfite to the mixture to remove it.
2. Collect the organic layer (is it on top or bottom?).  Record the volume of the crude 1-bromobutane.  Dry your product with anhydrous Na₂SO₄ (add enough salt to remove the cloudiness, indicating water removal).  
3. Store you liquid product until the next lab period in a tightly closed container (you must use a lid or ground-glass stopper).

Day 2

Decant the clear, dried liquid into a 50- or 100-mL round bottom flask.  Be careful not to let any of the solid sodium sulfate crystals get into the distillation pot.

Discard any forerun but start collecting the sample that distills above 90-95^oC.  Continue to collect the 1-bromobutane up to its boiling point.

Collect your distillate in a previously weighed dry flask or vial.

Measure the mass, volume, and index of refraction of the purified product. Determine an IR of your collected sample.

Questions:

1. What is the difference between Na₂SO₄ (sodium sulfate) and Na₂SO₃ (sodium sulfite)? The Na₂SO₃ is used to convert Br₂ into Br^-, but the anhydrous Na₂SO₄ is used to dry your product.
2. What is the refractive index of your purified product?
3. What was the boiling point?
4. Explain why the upper phase, after reflux, contained the 2-bromobutane, even though its expected density is 1.276 g/cm³, and the density of water is ~1.00 g/cm³.  Think what is in the aqueous solution (e.g., what is the density of salt water?)
5. What is the theoretical yield of 1-bromobutane?  What is your actual yield of 1-bromobutane?  What is your percent yield of 1-bromobutane?
6. What is the purpose of the anhydrous Na₂SO₄?  Why is it important that none of the solid Na₂SO₄ be included in the final distillation of your 1-bromobutane?