Santa Barbara City College Chemical Engineering Mentor: Lindsay - PowerPoint PPT Presentation

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

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

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

Methods  Reaction Setup  Monitor by T hin L ayer C hromatography Silica Plate Inlet Adapter Spots Reaction Flask Potassium Stir Plate Permanganate Stained  Characterization by H-NMR  Isolation – Column Chromatography 600 MHz NMR Silica Column Spectrometer Collection Tubes

Screening Results  N-Methylpyrrole 1. TFA 2. NIS 3. THF - 40° C, 30 min 100% Conversion 97% Trace Amounts • Reagents • T ri F luoroacetic A cid (TFA) • N - I odo S uccinimide (NIS) NOTE: Product hard • T etra H ydro F uran (THF) to isolate due to volatility

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

Screening Results  N-Methylpyrrole NO RXN 1. NIS 2. TFA Reflux, Overnight NO RXN • Reagents • T ri F luoroacetic A cid (TFA) • N - I odo S uccinimide (NIS) NOTE: Started at 0 ° C brought to reflux

Screening Results  Dibenzofuran 1. NIS 2. HFIP R.T, Overnight 64.5% Conversion • Reagents • N - I odo S uccinimide (NIS) • H exa F luoro-2- P ropanol (HFIP)

Screening Results  Dibenzofuran 1. NIS 2. TFA 50 ° C, 15 min 88% Conversion 84% 4.0% • Reagents • N - I odo S uccinimide (NIS) NOTE: Solution solidified at 15 min • T ri F luoroacetic A cid (TFA)

Screening Results  Dibenzofuran NO RXN 1. TFA 2. THF 3. NIS 50 °C, Overnight NO RXN • Reagents • T ri F luoroacetic A cid (TFA) • N - I odo S uccinimide (NIS) NOTE: Started at 0 ° C brought to 50 ° C • T etra H ydro F uran (THF)

97%

Accomplishments Skills – Organic Chemistry Lab Work - R un a quality reaction from start to end - I dentify products - I solate products Presentation and Communication - P ower Point Presentations -P ublic Speaking Practice - C onveying Scientific Information

Now what? Simple! Screen More Substrates!

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

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