1. Developing Methods for Regioselective Iodination of
Heterocycles in Mild Conditions
Christopher Bilham
Santa Barbara City College
Chemical Engineering
Mentor: Lindsay Smith Faculty Advisor: Armen Zakarian

2. Synthesizing a Better Future
Big Picture
Develop methods for effective iodination of a class of
compounds known as heterocycles
• Low Cost/High Yield
• Synthetically useful
Applications
• Pharmaceuticals
• Materials
• Agrochemicals
• Organic Synthesis
• Mild Conditions
• Regioselective
Lipitor
By Pfizer

3. Project Goals Summer 2013
 Substrates – ‘Starting Material’
 Screen these substrates under different conditions
2 – Methoxypyridine Dibenzofuran N-Methylpyrrole
GOAL: Screen all substrates and develop a comprehensive
understanding of the reaction methods and their effectiveness

4. Methods
 Reaction Setup
 Isolation – Column Chromatography
 Monitor by Thin Layer Chromatography
 Characterization by H-NMR
Inlet Adapter
Reaction Flask
Stir Plate
Silica Column
Collection Tubes
600 MHz NMR
Spectrometer
Silica Plate
Spots
Potassium
Permanganate
Stained

5. • Reagents
• TriFluoroacetic Acid (TFA)
• N-IodoSuccinimide (NIS)
• TetraHydroFuran (THF)
Screening Results
 N-Methylpyrrole
NOTE: Product hard
to isolate due to
volatility
Trace Amounts
1. TFA
2. NIS
3. THF
- 40° C, 30 min
97%100% Conversion

6. • Reagents
• N-IodoSuccinimide (NIS)
• HexaFluoro-2-propanol (HFIP)
Screening Results
 N-Methylpyrrole
NOTES: Thin Layer Chromatography
showed formation of product at room
temp after 30 minutes but no product
was isolated in the morning.
1. NIS
2. HFIP
R.T, Overnight
Unknown Conversion

7. • Reagents
• TriFluoroacetic Acid (TFA)
• N-IodoSuccinimide (NIS)
Screening Results
 N-Methylpyrrole
NOTE: Started at 0 ° C brought to reflux
NO RXN
NO RXN
1. NIS
2. TFA
Reflux, Overnight

8. • Reagents
• N-IodoSuccinimide (NIS)
• HexaFluoro-2-Propanol (HFIP)
Screening Results
 Dibenzofuran
1. NIS
2. HFIP
R.T, Overnight
64.5% Conversion

9. • Reagents
• N-IodoSuccinimide (NIS)
• TriFluoroacetic Acid (TFA)
Screening Results
 Dibenzofuran
NOTE: Solution solidified at 15 min
1. NIS
2. TFA
50 ° C, 15 min
84% 4.0%
88% Conversion

10. • Reagents
• TriFluoroacetic Acid (TFA)
• N-IodoSuccinimide (NIS)
• TetraHydroFuran (THF)
Screening Results
 Dibenzofuran
NO RXN
NO RXN
1. TFA
2. THF
3. NIS
50 °C, Overnight
NOTE: Started at 0 ° C brought to 50 ° C

11. 97%

12. Accomplishments
Skills – Organic Chemistry Lab Work
-Run a quality reaction from start to end
-Identify products
-Isolate products
Presentation and Communication
-Power Point Presentations
-Public Speaking Practice
-Conveying Scientific Information

13. Now what?
Simple!
Screen
More
Substrates!

14. Acknowledgements
Mentor: Lindsay Smith Faculty Advisor: Armen Zakarian
The Zakarian Group
-Dr. Armen Zakarian
-Lindsay Smith
-Aaron Herrmann
INSET
- Dr. Jens-Uwe Kuhn
- Dr. Maria Napoli
- Dr. Nick Arnold
- Assisting Faculty

15. General Equipment Questions