High throughput physical organic chemistry: analytical constructs for monomer reactivity profiling

Area of Science:

• Organic Chemistry
• Analytical Chemistry
• Polymer Science

Background:

• The Ugi four-component condensation is a versatile reaction for synthesizing complex molecules.
• Quantifying monomer reactivity in multi-component reactions can be challenging.
• Accurate reactivity data is crucial for optimizing synthetic strategies.

Purpose of the Study:

• To develop and validate a polymer-supported analytical construct for quantifying monomer reactivity in Ugi reactions.
• To utilize positive electrospray ionization mass spectrometry (MS) as a direct quantitative tool.
• To enable rapid assessment of monomer reactivity and reaction conditions.

Main Methods:

• A polymer-supported analytical construct featuring a bromo group and a quaternary ammonium moiety was synthesized.
• The construct was used to cleave and analyze adducts via positive electrospray ionization mass spectrometry (MS).
• Relative reactivities of carboxylic acids, isonitriles, and aldehydes were quantified based on MS-determined product levels.

Main Results:

• The construct effectively acted as a peak splitter and MS sensitizer for direct quantitation.
• Relative reactivities of 10 carboxylic acids, 10 isonitriles, and 10 aldehydes were successfully quantified.
• The method allowed rapid determination of concentration effects on monomer reactivity and product profiles.

Conclusions:

• The developed polymer-supported analytical construct provides a robust method for quantifying monomer reactivity in Ugi reactions.
• This approach facilitates the study of multiple reactions with diverse monomers in a single pot under controlled conditions.
• The method enhances efficiency and accuracy in assessing components for complex organic synthesis.