Unexpected polymorphism during a catalyzed mechanochemical Knoevenagel condensation
Sebastian Haferkamp1,2, Andrea Paul1, Adam A L Michalchuk1
1BAM Federal Institute for Materials Research and Testing, Richard-Willstaetter-Straße 11, 12489 Berlin, Germany.
Beilstein Journal of Organic Chemistry
|June 6, 2019
Summary
Ball milling a fluorinated benzaldehyde reaction with malonodinitrile produced different crystal forms. Catalyst amount influenced the crystallization pathway, affecting the final product
Area of Science:
- Solid-state chemistry
- Organic synthesis
- Mechanochemistry
Background:
- Knoevenagel condensation is a fundamental organic reaction.
- Polymorphism significantly impacts material properties and reaction outcomes.
- Mechanochemistry offers solvent-free synthesis routes.
Purpose of the Study:
- Investigate the in situ polymorphic transformations during a base-catalyzed, mechano-assisted Knoevenagel condensation.
- Determine the influence of catalyst concentration on reaction pathways and product crystallization.
- Explore the use of in situ Raman spectroscopy and multivariate analysis for monitoring complex solid-state reactions.
Main Methods:
- Ball milling of mono-fluorinated benzaldehyde derivatives and malonodinitrile.
- In situ monitoring using Raman spectroscopy.
- Mass spectrometric analysis for catalyst inclusion.
- Multivariate analysis of spectral data.
Main Results:
- The para-substituted product crystallized into two distinct polymorphic forms (monoclinic and triclinic) based on catalyst quantity.
- Low catalyst concentrations led to initial formation of a metastable monoclinic phase, converting to a stable triclinic phase upon further milling.
- Higher catalyst concentrations resulted in direct crystallization of the triclinic phase.
- Catalyst inclusion in the final product suggests seeding effects influence the polymorphic pathway.
Conclusions:
- The study elucidates a complex polymorphic pathway in a mechano-assisted Knoevenagel condensation.
- Catalyst concentration is a critical factor controlling the crystallization behavior.
- In situ Raman spectroscopy coupled with multivariate analysis provides a powerful tool for real-time monitoring of multi-phase mechanochemical reactions.
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