Experiment 10

Objectives

The aromatic ring is exceptionally stable due to resonance and the so-called aromatic stabilization.  Few reactions disrupt this thermodynamic stability. Therefore, most of the reactions that involve compounds with the aromatic ring do nothing to change the aromatic nature of that ring.  Such is the case in the experiment outlined here.  Electrophilic Aromatic Substitution (EAS) is the name given to a reaction that allows an electrophile (a Lewis acid) to replace (substitute for) a H⁺ on the ring.  In essence, a positively charged electrophile substitutes for an outgoing positive electrophile (H⁺).  This is EAS. In the current experiment a nitronium ion (NO₂⁺), prepared by mixing concentrated nitric and sulfuric acids, will get attached to the aromatic ring and the H⁺ ion released.

Background

The benzene ring is a component of many important natural products and other useful organic compounds. The ability to put substituent groups on a benzene ring, at defined positions relative to each other is a very important factor in synthesizing many new organic compounds. The two main reaction types used for this type of reaction are substitution reactions: Electrophilic Aromatic Substitution (EAS) and Nucleophilic Aromatic Substitution (NAS). The benzene ring itself is electron-rich, which makes NAS difficult, unless there are a number of strong electron-withdrawing substituents on the ring (e.g., aryl halides with multiple fluoride atoms being attached or other aryl halides with nitro groups attached) . EAS, on the other hand, is a very useful method for putting many different substituents on a benzene ring, even if there are other substituents already present. Chapter 12 in Organic Chemistry, by Carey, describes the factors involved in the regioselectivity for EAS reactions using benzene rings which already have substituents on them.

In this experiment you will attach a nitro (—NO₂) group onto a benzene ring which already has an ester group attached to it (methyl benzoate). The actual electrophile used in this reaction is the nitronium ion (NO₂⁺), which is generated in situ ("in the reaction mixture") using concentrated nitric acid and concentrated sulfuric acid (see Carey and your lecture notes for the mechanism):

Product Name: Methyl m-nitrobenzoate (Information about naming esters is available online)

Note that only one product is isolated. Why is this the only product?  (You should draw resonance structures for the anticipated [meta-substitution] as well as ortho- and para-substituted products.)  Why is the ester group electron withdrawing?

Procedure

The protocol is fairly straightforward. The reaction must be performed in strongly acidic conditions in order for production of the nitronium ion, which, as an electrophile is a Lewis acid. Please be aware of safety considerations, and be careful in all aspects of this reaction.

Safety: Concentrated nitric acid and concentrated sulfuric acid are both strong oxidizers, and highly corrosive — wear gloves while handling them, and avoid breathing their vapors. Methyl benzoate and methyl m-nitrobenzoate are irritants — wear gloves while handling them. Methanol is a flammable liquid, and is toxic  — no flames will be allowed in lab, wear gloves while handling it, and avoid breathing its vapors.

Day 1

To initiate your reaction, prepare the reaction mixture as follows:

1. Add 3 mL of concentrated sulfuric acid to a 125-mL Erlenmeyer flask.  Let this flask, and its contents, cool in an ice bath (or ice-water mixture) for 5-10 minutes. (It must be close to 0 °C, but do not measure the temperature with a digital thermometer, since the probe will get corroded.)
2. Add 12 mmol methyl benzoate (you will be given 1.50 mL; calculate the exact mass added using volume and density) to the cold sulfuric acid in the 125-mL flask from step #1. (You could weigh out the methyl benzoate, just be ultra careful not to spill.)   
3. Let the sulfuric acid and methyl benzoate mixture sit on ice for an additional 5 minutes (do not worry about any color changes).

After preparing your reaction mixture above, you will need to make a solution containing both concentrated nitric and sulfuric acids. This will be the solution containing the nitronium ion (NO₂⁺) used to attach the nitro group (—NO₂) to the benzene ring.

1. To prepare your H₂SO₄/HNO₃ mixture (nitration reagent), add 1 mL of concentrated sulfuric acid to 1 mL of concentrated. nitric acid in a small test tube. Mix the contents of this tube thoroughly, and cool this mixture in an ice bath until ready to use in the next step.  This mixture must be ice-cold prior to adding to the reaction flask.
2. Using a Pasteur or disposable pipette, slowly add (drop-by-drop) the H₂SO₄/HNO₃ mixture to the reaction flask containing the H₂SO₄/methyl benzoate mixture. After each drop is added, or while adding each drop, swirl the mixture in the flask to insure even and uniform mixing. This addition may take 5-10 minutes. After every few drops, place the flask for a brief period of time into the ice bath to keep the reaction cold.

When the addition of the concentrated H₂SO₄/HNO₃ mixture has been completed, let the entire reaction mixture (in the flask) warm to room temperature by letting the flask sit on the bench. Be certain to allow the reaction mixture stand for about 15 minutes after acid addition has been completed in order to allow the reaction to go to completion.

1. Pour the entire warm (room temperature) reaction mixture onto about 10 g of crushed ice
   • You do no need to weigh the ice, so just add enough ice to come up to about the 20-mL mark on a 50-mL beaker
   • Too much ice is not a problem, because all of the ice will melt.
   • The ice is used both to create the insoluble product, and to keep the diluted mixture cold.
2. When all the ice is melted, isolate the solid product by vacuum filtration using a small Büchner funnel.

If you do not store your solid product until the next lab period, but decide to do a re-crystallization today, save a small amount of this crude material in a labeled test tube until the next lab period in order to do a melt point determination. Do not seal the tube, since this would prevent evaporation of solvent.

Day 2

Recrystallize your crude product (collected via vacuum filtration during Day 1) using methanol as your recrystallization solvent.

Use a minimal amount of solvent for this recrystallization, and following the recrystallization protocols from previous experiments (if you think you are not getting a good yield, evaporate some of the methanol), isolated your recrystallized solid.

Record your product yield (both the crude and recrystallized product), melt points, and IR (optional: only if instructed on how to do an IR of a solid sample) of the purified product.  

Show your sample to your instructor.

Questions

1. Show the mechanism by which you produce the nitronium ion starting with nitric acid in the presence of concentrated sulfuric acid.
2. Show a reaction mechanism for the EAS of the nitronium ion for the H⁺ ion, which is the leaving group.
3. Why is the meta-substitution the preferred, and essentially only product?
4. If you started with 4.5 mL of methyl benzoate, how many grams of methyl benzoate would that be? What would be the theoretical yield of product, using that 4.5 mL of methyl benzoate?