Developing Methods for Regioselective Iodination of
Heterocycles in Mild Conditions
Christopher BilhamSanta Barbara City College
Chemical Engineering
Mentor: Lindsay Smith Faculty Advisor: Armen Zakarian
Synthesizing a Better Future Big PictureDevelop 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
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
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
• Reagents• TriFluoroacetic Acid (TFA)• N-IodoSuccinimide (NIS)• TetraHydroFuran (THF)
Screening Results
N-Methylpyrrole
NOTE: Product hard to isolate due to volatility
Trace Amounts
1. TFA2. NIS3. THF
- 40° C, 30 min
97%100% Conversion
• 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. NIS2. HFIP
R.T, Overnight
Unknown Conversion
• Reagents• TriFluoroacetic Acid (TFA)• N-IodoSuccinimide (NIS)
Screening Results
N-Methylpyrrole
NOTE: Started at 0 ° C brought to reflux
NO RXN
NO RXN
1. NIS2. TFA
Reflux, Overnight
• Reagents• N-IodoSuccinimide (NIS) • HexaFluoro-2-Propanol (HFIP)
Screening Results
Dibenzofuran
1. NIS2. HFIP
R.T, Overnight
64.5% Conversion
• Reagents• N-IodoSuccinimide (NIS) • TriFluoroacetic Acid (TFA)
Screening Results
Dibenzofuran
NOTE: Solution solidified at 15 min
1. NIS2. TFA
50 ° C, 15 min
84% 4.0%88% Conversion
• Reagents• TriFluoroacetic Acid (TFA)• N-IodoSuccinimide (NIS)• TetraHydroFuran (THF)
Screening Results
Dibenzofuran
NO RXN
NO RXN
1. TFA2. THF3. NIS
50 °C, Overnight
NOTE: Started at 0 ° C brought to 50 ° C
97%
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
Now what?
Simple!
Screen
More
Substrates!
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
General Equipment Questions
