Chemistry 3231 – Organic Chemistry III

Laboratory Report for Experiment #2 – "Sulfa Drugs: The Synthesis of Sulfanilamide"

Objective: To study the reactions necessary to synthesize the sulfa drug sulfanilamide from acetanilide.

Theory:The series of reactions are broken up into 3 steps. First, the prepared acetanilide is reacted with the chlorosulfonic acid. The acetamide group being a para director causes the chlorosulfonic acid to react at the para (or 4 position) to the acetamide position (making 4-acetamidobenesulfonyl chloride). Secondly, the now sulfonic substituent is reacted with ammonia (in this case NH4OH) in order for the acyl chloride to be replaced with an amino group, making a sulfanamide (4-acetamidobenesulfonamide). Finally, the acetamide is then removed to make the sulfanilamide (4-aminobenzenesulfonamide). It is well to note that the final step is required due to the fact that the final product is an aromatic amine. We could not have the amino group ‘free’ throughout the reaction, or else the chlorosulfonic acid would have attacked that amino group instead of the ammonia we added to the solution later. The acetyl group acts as a sort of protection for that possibility. A thorough workthrough of the reaction is attached:

Table of Chemicals:

Reagents/Products

Amount Used

Molecular Weight

Concentration

Comments
Acetanilide 6.9 g

(0.05104 mol)

 135.17 Pure Reagent
Chlorosulfonic acid 14 mL

(~0.2 mol)

 116.52 ~15M Reagent
Hydrochloric acid N/A; 9.85 g 36.45 N/A; dil (~6M) Evolved from the chlrosulfonic acid reaction, as well as used to set reaction conditions when removing the acetyl group from the acetamide
p-acetamidobenzene

sulfonyl chloride

 Unknown 233.67 Unknown Product from step (a) mp – 148-150oC
p-acetamidobenzene

sulfonamide

 4.9293 g

(0.02300 mol)

 214.24 Unknown Product from step (b) mp – 219oC
p-aminobenzene

sulfonamide

 3.71 g

(0.02154 mol)

 172.21 Unknown (assumed pure) Final product Observed mp – 165.7oC. (mp – 163oC)
ICE ~250 g 18.02 N/A Used to cool the product from step (a). mp – 0oC
Sodium Carbonate ~20 mL 105.99 Saturated solution Used to ‘sop up’ any excess acid.

Experimental Procedure:

Results:

Observations:

Again, the low yieldage (as will be shown) can possibly be attributed to mainly mechanical loss, as well as this was a 3 step process in which there can be a lot lost. For example if I had a 70% yield in each step, calculations would show that only 3.0148322512g can be expected. So, overall the yieldage was low, but in each individual step there was a high yield (at least 70% or more)

Yield Data:

%Yield

= (0.02154 mol / 0.05104 mol) x 100%

= 42.2021%

Spectral Data:

No spectral data was obtained for this experiment.

Reference(s):