<< Chapter < Page Chapter >> Page >

Mutli step synthesis

Synthesis of sulfanilamide


In this lab we will synthesize sulfanilamide starting with aniline. Our synthetic steps will include a protection of an amine, followed by chlorosulfonylation of the protected aniline. This compound is then deprotected and converted to our target molecule, sulfanilamide, in one final step.


You will be assessed on:

  • Write-up in your Lab Notebook
  • TA evaluation of lab procedure
  • Answers to Post Lab questions


Sulfa drugs have been a very integral part of our medical history. Sulfa drugs were first used in the 1930’s, and are now the oldest antibiotics available and also among the best. Sulfa compounds work by inhibiting nucleic acid (DNA, RNA) synthesis. The way sulfa compounds work is by shutting down the system by which bacteria synthesize their folic acid. They do this by competing with para-aminobenzoic acid (PABA, necessary for folic acid synthesis). See Figure 1 to see if you can tell why sulfanilamide is a competitor for PABA.


1. Place 5mL conical vial, Claisen head,½dram vial, and a drying tube packed with glass wool and calcium chloride into the oven for 30 minutes at 125 ° C size 12{°C} {} . 2. Remove glassware from oven and allow it to cool.3. Measure out 230 μL size 12{μL} {} of aniline and 500 μL size 12{μL} {} of methylene chloride to the 5mL conical vial. 4. Immediately place the Claisen head equipped with a septum cap and the drying tube to the vial.5. Place the setup in an ice bath to cool the reagents before adding trifluoroacetic acid. 6. Once the reagents are cool (5 minutes), add 500 μL size 12{μL} {} of methylene chloride to a½dram vial. To this then add 500 μL size 12{μL} {} of trifluoroacetic acid. Draw up the 1 mL total of solution into a syringe and add it through the septum dropwise to the aniline solution.Note: The reaction is exothermic, if the addition is too rapid, the methylene chloride will evaporate. 7. After the addition is complete, let reaction stand at room temperature for 10 minutes.8. After reaction is at room temperature, remove the claisen head and remove methylene chloride by passing air over the top of the solution. This will evaporate the methylene chloride and residual trifluoroacetic acid, leaving the product as a white powder.


1. Place an air condenser and a 9-in Pasteur pipet calibrated to deliver 0.9 mL, into the oven for 30 minutes at 125 ° C size 12{°C} {} .2. Remove glassware from oven and allow it to cool.3. Attach the vial containing 2,2,2-trifluoracetanilide to the dry air condenser.4. Measure out 0.9 mL of chlorosulfonic acid with the pipet and slowly add it to the vial by inserting the pipet down the air condenser.5. Place vial with condenser attached into a sand bath and heat for 10 min. at 65 ° C size 12{°C} {} .6. Collect the precipitate by vacuum filtration and wash with three 1-mL portions of cold water.7. Let the product air dry. Determine the melting point and overall yield.8. Weigh out 400 mg of the p-(2,2,2-trifluoroacetamido)benzenesulfonyl chloride into a 10-mL Erlenmeyer flask.9. In a test tube measure out 0.6 mL of concentrated ammonium hydroxide and 0.4 mL deionized water.10. Add the ammonium hydroxide solution to the Erlenmeyer containing the p-(2,2,2-trifluoroacetamido)benzenesulfonyl chloride. Use a glass stirring rod to break up any chunks that form.11. Add a boiling stone to the Erlenmeyer flask and place the reaction mixture into a sand bath. Heat the reaction to boiling and watch for all the solid to dissolve. Once total dissolution has occurred boil the mixture for an additional minute.12. Once reaction is complete remove the flask from the sand bath and allow to cool to room temperature. Once this is done place the flask into an ice bath for 15 min.13. Collect the yellow crystals that precipitate out of solution and isolate them via vacuum filtration. Wash with three 0.5 mL portions of water to remove any soluble impurities.14. Let the product air dry. Determine the melting point and overall yield.

Post-lab questions:

1. Who won the Nobel Prize for the discovery of sulfanilamide drugs?

2. To give you a better idea of the massive amount and diversity of protecting groups, assign structures to the following list of protecting group abbreviations:AcAdBnBOCCbzFmocMEMONBPptTBDMSTfTHPTIPSTMSTos

A good ref. Protective Groups in Organic Synthesis by Theodora W. Greene3. How do sulfa drugs work?

4. Draw a mechanistic scheme for all reactions done in this lab. (Show correct arrow pushing, and mechanistic detail.)

Questions & Answers

how can chip be made from sand
Eke Reply
are nano particles real
Missy Reply
Hello, if I study Physics teacher in bachelor, can I study Nanotechnology in master?
Lale Reply
no can't
where we get a research paper on Nano chemistry....?
Maira Reply
nanopartical of organic/inorganic / physical chemistry , pdf / thesis / review
what are the products of Nano chemistry?
Maira Reply
There are lots of products of nano chemistry... Like nano coatings.....carbon fiber.. And lots of others..
Even nanotechnology is pretty much all about chemistry... Its the chemistry on quantum or atomic level
no nanotechnology is also a part of physics and maths it requires angle formulas and some pressure regarding concepts
Preparation and Applications of Nanomaterial for Drug Delivery
Hafiz Reply
Application of nanotechnology in medicine
has a lot of application modern world
what is variations in raman spectra for nanomaterials
Jyoti Reply
ya I also want to know the raman spectra
I only see partial conversation and what's the question here!
Crow Reply
what about nanotechnology for water purification
RAW Reply
please someone correct me if I'm wrong but I think one can use nanoparticles, specially silver nanoparticles for water treatment.
yes that's correct
I think
Nasa has use it in the 60's, copper as water purification in the moon travel.
nanocopper obvius
what is the stm
Brian Reply
is there industrial application of fullrenes. What is the method to prepare fullrene on large scale.?
industrial application...? mmm I think on the medical side as drug carrier, but you should go deeper on your research, I may be wrong
How we are making nano material?
what is a peer
What is meant by 'nano scale'?
What is STMs full form?
scanning tunneling microscope
how nano science is used for hydrophobicity
Do u think that Graphene and Fullrene fiber can be used to make Air Plane body structure the lightest and strongest. Rafiq
what is differents between GO and RGO?
what is simplest way to understand the applications of nano robots used to detect the cancer affected cell of human body.? How this robot is carried to required site of body cell.? what will be the carrier material and how can be detected that correct delivery of drug is done Rafiq
analytical skills graphene is prepared to kill any type viruses .
Any one who tell me about Preparation and application of Nanomaterial for drug Delivery
what is Nano technology ?
Bob Reply
write examples of Nano molecule?
The nanotechnology is as new science, to scale nanometric
nanotechnology is the study, desing, synthesis, manipulation and application of materials and functional systems through control of matter at nanoscale
how did you get the value of 2000N.What calculations are needed to arrive at it
Smarajit Reply
Privacy Information Security Software Version 1.1a
Got questions? Join the online conversation and get instant answers!
Jobilize.com Reply

Get Jobilize Job Search Mobile App in your pocket Now!

Get it on Google Play Download on the App Store Now

Source:  OpenStax, Chem 215 spring08. OpenStax CNX. Mar 21, 2008 Download for free at http://cnx.org/content/col10496/1.8
Google Play and the Google Play logo are trademarks of Google Inc.

Notification Switch

Would you like to follow the 'Chem 215 spring08' conversation and receive update notifications?