Sulfa Drug Group Project
Chemistry 258
Loyd D. Bastin
Brief History

1932-I.G. Farben (dye company in Germany)

1933-Prontosil used against staphylococcal septicemia
(blood infection)
1935-Gerhard Domagk


Prontosil cured streptococcal infections in mice and rabbits
Later

shown to have an even broader application
1939-Domagk earned Nobel Prize in medicine

Hitler did not allow him to accept
Was
later awarded the prize
More History

1935-J. Tréfouël
In vivo (in animals) prontosil effective
 In vitro (petri dish) prontosil ineffective
WHY?
 Tréfouël showed that prontosil was metabolized to sulfanilamide
in the body

Sulfanilamide
shown to have in vivo and in vitro activity
Led to an explosion in the synthesis of sulfanilamide analogs
Became the wonder drug of the 30s and early 40s
(referred to as sulfa drugs)
A Little More History



1929-Alexander Fleming discovers Penicillin G
1941-Penicillin G shown to be successful
antibacterial agent in humans
 Leads to a decline in use of sulfa drugs
However, sulfa drugs are still used for malaria,
tuberculosis, leprosy, meningitus, pneumonia, scarlet
fever, plague, respiratory, infections, and
intestinal/urinary tract infections
Synthesis
Your Task

Groups of 3 or 4




You are a team and it is your job to work together and synthesize
the appropriate number of sulfa drugs.
Choose the R groups and synthesize 3 (or 4) different sulfanilamide
analogs.



See handout for groups
Weekly group meetings with me to discuss your progress future plans
Group of 3 – synthesize 3 different sulfanilamide analogs
Group of 4 – synthesize 4 different sulfanilamide analogs
Design a “greener” experiment for one of your sulfanilamide analogs
Your Task Continued

Here are your possible R groups
Group A (Should wor k
well)
Group B (harder)
Group C (even Harder)
Ammonia
methyl benzy l ami ne
2-ami noace tophenone
2-aminothiazole
isopropyl amine
p-bromoanili ne
butyl ami ne
sec-butyl ami ne
o-anisidine
propyl ami ne
phene thyl ami ne
ethyl- 4-ami no benzoa te
benzy l ami ne
anili ne
2,4,6-tribromoanil ine
p-tolu idine
2-methyl-4-nit roanili ne
cyc lohexy l ami ne
2-methoxy-4 -nit roanili ne
p-ami nopheno l


It is your job to make the synthesis work. Use the procedures in the lab
manual, Pavia, and/or Shriner as GUIDELINES. Modifications will be
necessary. Could be as simple as changing T and/or solvent, or it could
require some research on your part. Use your time wisely and multi-task.
Your group must submit IN WRITING at your first group meeting, which
molecules you plan to synthesize. If you have trouble with compounds from
Groups B or C, you can update your target molecules after the first meeting.
However, you can NOT upgrade your target group after the first group
meeting. (example, you can not go from group A target to group B target)
Your Task Continued


If you change your plan, it must be submitted in writing and signed
by all group members.
Then you will test the antibacterial activity of your drugs against E.
coli.
The written lab report
52 points (total possible)
Successful synthesis of drug from group A: 4 pts (0 points if not made)
Successful synthesis of drug from group B: 7 points
"
Successful synthesis of drug from group C: 12 points
"
Examples: The total points possible for doing an amine from group A and 3 amines
from group C would be 92 points (52 + 4 + 12 +12 + 12). Total possible for doing 4
amines from group A would be 68 points (52 + 4 + 4 +4 +4).


You MUST prove the identity and purity of your compound to receive
all of the points using mp, NMR, IR, and/or TLC
We will do NMR once you have purified your product and shown this
by TLC.
Final Report



Each group will submit ONE report.
Each member will submit a grade sheet for each member of their
group
For details please see pg. 33 in lab manual and then ask me if you
have any questions.