Experiment 8

Objectives

Background

This experiment, like the ones preceding it, will be carried out with the specific purpose of making a new compound. It is your responsibility to read through the procedure carefully (before coming to class) and look up in Zubrick any laboratory techniques being used.  You must understand the procedure well enough to be able to go into lab, get set up, and execute the necessary steps quickly, efficiently, and accurately. Be sure to plan ahead so that you, or your partner, can assemble the simple distillation apparatus without help from others in the lab. 

Nucleophilic substitutions are one of the most generally useful classes of synthetic organic reactions we encounter.  Alcohols, in fact, are probably one of the most useful organic chemical available since they can be used as a starting component for many different reactions.  Also, because of their high boiling points, other chemicals can often be prepared from them, and isolated via distillation since they usually will have lower boiling points.  Hence, your product, which can easily be converted into the gas phase can be isolated even before all of the reaction has occurred.  The physical removal of desired product (like the 2-pentene in a previous experiment) favors the formation of more product. The particular class of experiment is a second order nucleophilic substitution, specifically S_N2.

As discussed in lecture, an S_N2 reaction requires three things: (i) a nucleophile, (ii) an electrophile, and (iii) a good 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° carbon), 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 (reaction is performed in an acidic solution and water will be the leaving group),

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

we see that the first two criteria are satisfied (the bromide ion is an excellent nucleophile and the electrophile is a 1° alkyl group).  Since the alcohol functional group (–OH) would be a poor leaving group, due to its negative charge and high basicity, it must be modified to make it into a better leaving group.  This can be done in acid (producing the alkyloxonium ion) which would then come off as a water molecule (a good leaving group).

So, whenever presented with a situation like this, it is important to ask yourself the following question: "How can we make OH^- into a better leaving group?"  Obviously we have a few choices.  Making it into a water-molecule leaving group, as discussed above is a good choice.  Alternatively, we have other choices as well.  These are: (i) 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; (ii) 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 (iii) using a strong acid (as outlined above) to protonate the –OH group in the presence of the bromide ion, which then changes the leaving group from hydroxide ion into water, and allows the bromide to react with it in the same mixture. We will use the last of these methods.

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.

Procedure

Add 20.0 g of solid sodium bromide (NaBr) to the 250-mL round bottom flask, which will be your reaction flask.

Add 15.0 mL of DI water to the flask and swirl to mix with the NaBr, but most of the salt will not dissolve.  This is okay. Everything will dissolve when the reaction flask is heated.

Place the reaction flask in a beaker containing ice to cool.

Add 15 mL of 1-butanol to this salt mixture.

Slowly add 15 mL of concentrated sulfuric acid to the contents of the flask by placing a funnel in the side-arm of the flask and gently pouring the acid into the flask, letting the acid run down the side.  After each 5 mL of acid addition, swirl the flask to mix its contents. Keep the flask cold, sitting in the ice bath until all the acid is added.

Assemble the reaction flask into a reflux setup, by placing the condenser unit into the top of the flask.  Turn on the water to begin circulating through the column.  Turn on the heating mantle, and start the reaction going.  When the reaction mixture starts to boil, start timing the 45-min reflux period.

As hot vapors are produced in the reaction flask, they will move upward into the reflux column where they will hit the sides of the column, condense and run back into the reaction flask.  By this time all  using only the condenser tube attached to the flask (a drying tube is not used). Don't forget to add a few boiling stones.

pouring about 1 mL at time to the flask.  Let the acid run down the inside wall of the flask (you can use the side arm to add the acid).

1. Add 20.0 g of sodium bromide and 15 mL of water into the 250-mL round bottom flask.
2. Swirl the flask until all (or most) of the sodium bromide is dissolved (some crystals remaining will be okay, s).
4. Place the flask, containing the above reaction mixture, in the ice-water bath (make sure the flask cannot tip over!!).
6. Gently swirl the flask to mix the contents after each addition (be careful, and don't add the acid too fast).
8. Reflux the mixture for 45 minutes, making sure the reflux vapor ring does not rise above the halfway point of the condenser. 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 as cooled somewhat, use the reaction flask as the distillation pot for a simple distillation.
10. Heat reaction mixture and collect everything that has a boiling point of up to about 105°C. When the temperature reaches 105°C, continue to boil the mixture and collect the distillate.  You should test the distillate every 2 or 3 minutes to see if it is still water-insoluble (add the distillate to a tube of water, and see if a separate, organic phase is sill present). When there appears to be no more water insoluble droplets coming across, turn off the heat. Once the distilling flask has cooled, dispose of its strongly acidic waste in the appropriate waste container. The distillate contains both water and the product, 1-bromobutane, with a little sulfuric acid mixed in.
11. Using a separatory funnel, wash the distillate with about 20 mL of a 5% 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.
12. 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).  
13. Store you liquid product until the next lab period in a tightly closed container (you must use a lid or ground-glass stopper).

Purify the 1-bromobutane by simple distillation.

Pour the clear, dry liquid into a 50- or 100-mL round bottom flask.  Be careful not to let any solid crystals go 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 flask or vial.

Measure the mass, volume, and index of refraction of the purified product.

 Put all of the 1-bromobutane in a sample vial labeled with your name: name of compound, mass, volume, index of refraction, and names of people in the group. Wrap the cap with parafilm and give the vial to your instructor.

Questions:

1. What is the difference between Na₂SO₄ (anhydrous sodium sulfate) and Na₂SO₃ (sodium sulfite)?
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?

Required Equipment:

1. 250-mL Round Bottom flask used as the reaction vessel
2. Condenser unit attached to top of reaction flask with attached hoses for water cooling
3. 250-mL heading mantle and power supply
4. A simple distillation setup for collecting reaction product
5. Separatory funnel
6. 25-mL or 50-mL round bottom flask for storage with a ground-glass stopper