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Sulfa Drug Group Project
Chemistry 258
Loyd D. Bastin
Brief History
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1932-I.G. Farben (dye company in Germany)
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1933-Prontosil used against staphylococcal septicemia
(blood infection)
1935-Gerhard Domagk
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Prontosil cured streptococcal infections in mice and rabbits
Later
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shown to have an even broader application
1939-Domagk earned Nobel Prize in medicine
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Hitler did not allow him to accept
Was
later awarded the prize
More History
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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
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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
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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
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Groups of 3 or 4
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Select groups
Weekly group meetings with instructor to discuss your progress and
future plans
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.
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Group of 3 – synthesize 3 different sulfanilamide analogs
Group of 4 – synthesize 4 different sulfanilamide analogs
Design a “greener” method for one of your group C sulfanilamide
analogs
If you change your plan, it must be submitted in writing and signed
by all group members.
You MUST prove the identity and purity of your compound using mp,
1H-NMR, IR, and/or TLC to receive full credit
We will do 1H-NMR once you have purified your product.
Finally, you will test the antibacterial activity of your drugs against E.
coli.
Your Task Continued
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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-aminoace tophenone
2-aminothiazole
isopropyl amine
p-bromoanili ne
butyl amine
sec-butyl amine
o-anisidine
propyl amine
phene thyl amine
ethyl- 4-ami no benzoa te
benzy l amine
anili ne
2,4,6-tribromoanil ine
p-tolu idine
2-methyl-4-nitroanili ne
cyc lohexy l amine
2-methoxy-4 -nit roanili ne
p-aminopheno l
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It is your job to make the synthesis work. Use the procedures in the lab
manual as GUIDELINES. Modifications may/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 during the first lab meeting, which
molecules you plan to synthesize, 2-3 procedures that the group will initially
dry, and a list of IR peaks you will use to indicate if a reaction occurred. If
you have trouble with compounds from Groups B or C, you can update your
target molecules and methods. However, you can NOT upgrade your target
group after the first lab meeting. We want to be GREEN.
Rough Schedule
Week 1
Groups must submit in writing within the first 1.5 hours of the 1st lab meeting.
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List of Group Members
Amines to be used initially and reasoning behind those choices
2-3 procedures that the group will try initially and the reasoning behind those choices
List of IR peaks that your group will use to indicate if a reaction has occurred.
Weeks 1, 2, and 3
Work on step 1. Group meetings
Week 4
Work on hydrolysis step. Group meetings
Weeks 5 and 6
Work on greener method. Group meetings
Week 7
Test antibacterial activity of sulfa drugs. Finish any characterization
Final Report
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Each group will submit ONE report.
Each member will submit a peer evaluation sheet for each member
of their group
The written lab report
Successful synthesis of drug from group A:
Successful synthesis of drug from group B:
Successful synthesis of drug from group C:
Successful “greener” synthesis of a sulfa drug:
Peer evaluation of group work:
Instructor evaluation of group work:
Total points for the report
60 pts (total possible)
4 pts
8 pts
12 pts
12 pts
8 pts
4 pts
120 points
Examples: The total points possible for doing an amine from group A and 2 amines from group
C and devising a greener method would be 112 points (60 + 4 + 12 +12 + 12 + 8 + 4). Total
possible for doing 3 amines from group A and devising a greener method would be 96 points (60
+ 4 + 4 + 4 + 4 + 8 + 4).
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For details please see pg. 181 in the lab manual and then ask me if
you have any questions.