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Scalable Mechanochemical Synthesis of Biotin[6]uril
Elina Suut-Tuule1, Eve Schults1, Tatsiana Jarg1
1Department of Chemistry and Biotechnology, Tallinn University of Technology, Akadeemia tee 15, Tallinn, 12618, Estonia.
Chemsuschem
|January 2, 2025
Summary
A new mechanochemical method synthesizes biotin[6]uril, a chiral macrocycle, with high yield and purity. This solid-state approach offers a scalable, efficient, and environmentally friendly alternative to traditional solution-based synthesis.
Area of Science:
- Supramolecular Chemistry
- Organic Synthesis
- Materials Science
Background:
- Biotin[6]uril is a chiral, water-soluble macrocycle with anion-binding properties.
- Dynamic covalent chemistry is a key strategy for constructing complex molecular architectures.
- Efficient synthesis of macrocycles is crucial for their application in various fields.
Purpose of the Study:
- To develop a scalable and high-yielding synthesis of biotin[6]uril.
- To explore a mechanochemical solid-state approach for macrocycle formation.
- To compare the mechanochemical method with conventional solution-based synthesis.
Main Methods:
- Mechanochemical synthesis involving grinding d-biotin and paraformaldehyde with aqueous HBr catalyst.
- Solid-state reaction utilizing a shaker or planetary mill.
- Post-reaction aging at elevated temperatures.
- High-Performance Liquid Chromatography (HPLC) for yield and purity determination.
Main Results:
- Achieved up to 96% HPLC yield of biotin[6]uril.
- Successfully scaled up the reaction 82-fold, producing nearly 20g.
- Obtained high isolated yield (92%) and purity (91%).
- Demonstrated significantly higher yields and shorter reaction times compared to solution methods.
Conclusions:
- The mechanochemical solid-state approach provides a superior method for biotin[6]uril synthesis.
- This method offers advantages in yield, scalability, operational simplicity, and reduced process mass intensity.
- The developed protocol is a promising advancement for the efficient production of biotin[6]uril.
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