Purpose:
You will carry out the multi-step synthesis of the epoch-making antibacterial drug, sulfanilamide.
Reactions and Physical Properties:Procedure:Day 1 (3/19):
Carry out everything in the hood! To a dry dram vial with a stir bar, add dichloromethane (0.5 mL) and aniline (2.50 mmol). Immediately cap the vial with a rubber septum. Place this vial in a cold water bath. To a separate dry dram vial, add dichloromethane (0.5 mL) and trifluoroacetic anhydride (TFAA, 3.54 mmol). TFAA hydroyzes rapidly in moist air, so make the transfer quickly.
Using a needle, add the TFAA solution dropwise to the aniline solution. You will want to vent the septum with an additional needle. Heat is produced in the reaction. If the addition is too rapid, the methylene chloride starts to reflux and fumes are emitted. After the addition is complete, allow the reaction to stir at ambient temperature for 10 min.
Remove the septum from the reaction vial and,
in the hood, concentrate the solution on a warm sand bath under a slow stream of air. The crude 2,2,2-trifluoroacetanilide intermediate is obtained as a white powder. Cap the vial. The crude material is not purified further, but rather used directly in the next reaction of the sequence without further characterization. Label the vial, seal the cap with parafilm, and place in the fridge until next week.
Day 2 (3/26):
Remove your product from the fridge from week 1. Carefully transfer your product and stirbar to a 5-10 mL round-bottom flask, and attach a microscale reflux condenser (you do not need to hook up water to the condenser).
Very carefully measure out chlorosulfonic acid (13.7 mmol) into a dry dram vial.
CAUTION: Chlorosulfonic acid is a very corrosive substance. It reacts violently with water and causes serious burns on contact with the skin.
Dispense the reagent in the hood and wear gloves.
Very carefully and slowly add the chlorosulfonic acid to the reaction vessel through the condenser by Pasteur pipet. Leave all equipment to transfer this material in the hood until it is obvious that the residual reagent has reacted with the moist air (white fumes subside), and leave these materials in contact only with glass surfaces.
Place the reaction vessel on the hot plate (using a metal insulating block) and heat the mixture at 60-70 °C for 10 min.
Allow the reaction mixture to cool to ambient temperature, and place the flask in an ice-water bath. Using a new dry Pasteur pipet, transfer the cold reaction solution
slowly to a 10 mL beaker containing ice (approximately half full) in the
hood.
A precipitate of the product forms at this stage. Collect the tanish-white solid by vacuum filtration and wash the filter cake with ice-cold water (3 x 1 mL). Allow the material to air-dry. Determine the weight of the crude product, and calculate the percent yield from aniline. Determine its melting point, and compare it to the reported value of XXXXXXXXXX °C.
Day 3 (4/2):
Place your solid product from day 2 in a 5-10 mL round-bottom flask with a stir bar. In a dram vial, prepare a solution of concentrated aqueous ammonium hydroxide (0.6 mL) and DI water (0.4 mL). Add this solution to the solid sulfonyl chloride in the flask. Heat the reaction with stirring XXXXXXXXXX °C) until the solid dissolves. You might need to use a glass stir rod to help break up the chunks. Following dissolution, heat the solution to boiling for an additional minute.
Transfer the reaction to a small beaker, let cool to ambient temperature, then in an ice-water bath for 20 min. During this time light-yellow crystals of product precipitate (say that 10 times fast). Collect the product by vacuum filtration, washing the crystals with ice-cold water (3 x 0.5 mL). Air dry the sulfanilamide, weigh, and calculate a crude yields, both for this step and the overall sequence.
Recrystallize the product from water, and let sit in a dessicator overnight. We will determine the mp, IR and NMR of this product.