Nitration of Aromatic Compounds

CH 228 Nitration of Aromatic Compounds

When performing a nitration you need to look at the compound you are nitrating and decide whether it is activated or deactivated, and where the substituents will attach to the ring – use your textbook (Chapter 16 of Bruice, 6th edition). There are several possibilities for your unknown compound.

CO2H NHCOCH3

Benzoic acid Naphthalene Acetanilide

O Cl

Benzophenone p-Dichlorobenzene

When nitrating an activated aromatic compound you need to exert extreme care!! Nitrations are exothermic and the products can be explosive, so be careful.

SAFETY Concentrated sulfuric and nitric acids are very corrosive and reactive materials and will dissolve you, your clothes, your papers, or anything else they touch! WEAR GLOVES WHEN HANDLING THESE CHEMICALS. If any should splash on you, wash the affected area with running water for at least five minutes and notify your instructor. Watch carefully for drips and runs on the outside surface of reagent bottles and graduated cylinders when you pick them up. Apply sodium bicarbonate (NaHCO3) solution to the area. This can be found in a squirt bottle in the hood with the other squirt bottles. Rinse your glassware thoroughly with water after usage.

Aromatic nitro compounds are often toxic and irritating when smelled or absorbed through the skin, avoid contact and handle in the hood.

1 NITRATION CONDITIONS Generally, nitrations are performed in a mixture of concentrated nitric and concentrated sulfuric acids. The mixture of these acids generates the nitronium ion, which is the species that attacks the aromatic ring.

Reaction:

H SO HNO HSO H O NO 2 4 + 3 4 + 2 + 2

Mechanism:

A few words of caution:

1. Nitrations are exothermic; make sure you cool the reaction in an ice bath. In organic lab the term “ice bath” really means “ice-water bath” so add a little water to your ice.

Cool a 50 mL Erlenmeyer flask containing a magnetic stir bar and 10 mL of the mixture of nitric acid and sulfuric acid (already mixed for you by stockroom personnel and in the hood) in an ice bath (clamp the neck of the Erlenmeyer flask to the support in your hood) on your hot plate – stirrer. Stir for 5 minutes and slowly begin to add 2 g of your aromatic compound. Use what chefs call a pinch of compound on the end of your spatula at a time. Let each pinch mix in, and then add the next, and so on until your entire compound has been added. The solid you add should dissolve. Observe carefully. Sometimes the solid starting material dissolves and the solid product forms without a student noticing.

Monitor the reaction by TLC:

To get a TLC sample you need to “work up” a small portion of the reaction mixture: Remove a few drops of the reaction mixture with a disposable pipet and transfer to a test tube containing 1-2 mL each of water and diethyl ether. Shake and use the ether layer (top layer) for spotting. Remember to use pure starting material (not from the reaction mixture) in a separate test tube dissolved in ether for comparison with your reaction mixture.

2. When you have stirred the reaction mixture in the ice-water bath for ten minutes after addition of starting material has been completed and the TLC still shows

2 presence of starting material, remove the flask from the ice-water bath and stir it unheated on the hot plate – stirrer. Allow the solution/mixture to warm to room temperature, monitoring the reaction mixture every ten minutes.

3. When the TLC indicates no further presence of starting material, work up the reaction by pouring into a large excess of cold water (100 mL in a 250 mL beaker) with care. The product should solidify immediately.

4. Vacuum filter.

5. If no solid forms after scratching with a glass rod, and standing in cold water, you may need to extract the product with ether using the standard extraction procedure.

6. Once you have isolated the solid CRUDE product by vacuum filtration, you need to recrystallize it:

a. Place your solid material in a 50 mL Erlenmeyer flask, add 10 mL of ethanol, add a wooden stick to facilitate boiling, and heat the mixture on a steam bath.

b. When (if) the solid dissolves, remove the solution from the heat, place the flask on the bench top and allow to cool.

c. If the solid does not dissolve before the solvent boils, add 5 mL more of ethanol. Continue heating and adding ethanol in 5 mL increments until all the solid dissolves, then place the flask on the bench top and allow to cool.

d. Once the solution has cooled enough that the flask is not too hot to touch, cool the flask in an ice-water bath for 5 minutes.

e. If the solid does not crystallize after cooling, return it to the steam bath, evaporate ½ of the volume of solvent and return to step b above.

f. Vacuum filter your recrystallized product and let it dry until the next lab period.

7. Characterize the product by IR, NMR, and mp. Compare your data with that of the known nitro aromatic compound, if available. How well does it match? Spectra are available on the CH 228 website. Record these data in your notebook.

WASTE DISPOSAL The initial filtrate from the nitration reaction may be poured into the acid waste bottle in the hood. The filtrate from the recrystallization can be poured into the liquid organic waste bottle in the hood.