1. General

Review the following topics: esterfication, infrared spectroscopy, NMR spectroscopy, mass spectrometry, electrophilic aromatic substitution

2. Esterification

a. Safety:

1. 85 % phosphoric acid is corrosive.

2.  95 % ethanol is flammable.


b. Experiment

It is very important that the phenol that is used in this reaction is properly dried. If you are not sure about it, place it under the heating lamp for 15 minutes to dry it a little more. It might be a good idea to acquire an infrared spectrum before the esterification is started to detect a larger amount of water.

Acetic acid anhydride doubles up as solvent and acid source in the reaction. It is also able to deal with a small amount of water in the system. Why?

The catalyst in the reaction is concentrated phosphoric acid (85 %), which is fairly corrosive (CAREFUL!). What else could be used as catalyst (Hint: Think green chemistry)?

The crude is purified by recrystallization from 95 % ethanol. Why?

3. Nitration

a. Safety note

1. Glacial acetic acid is corrosive.

2. Methanol is toxic and highly flammable.

3. Metal nitrates are oxidant. They should not be heated too high because they will react as such then.

Experiment:

The ester has to be dissolved in glacial acetic acid and acetic acid anhydride first. What is the function of the anhydride here?

The addition of magnesium nitrate results in a color change to yellow-orange. Why?

The reaction mixture is poured over ice, and not into cold water. Why?

The crude is recrystallized from a minimum amount of methanol.

4. Things to think about

a. How could the student determine if the esterfication reaction leads to the proposed O-acylation product or to the para C-acylation product?

b. Why do you have to control the temperature of the reaction mixture in the nitration reaction?

c. Excessive amount of methanol during the recrystallization step of the nitro compound will lead into a loss of product. How can the student troubleshoot the recrystallization?

d. How would the ¹H-NMR spectrum of the  (I) 2-nitroester   (II) 3-nitroester   (III) 2'-nitroester   (IV) 3'-nitroester    (V) 4'-nitroester  look like? How about the ¹³C-NMR spectra?