Abstract
Although known for millennia, it is only recently that mechanochemistry has received
serious attention by chemists. Indeed, during the past 15 years an extraordinary number
of reports concerning solid-state chemical transformations through grinding and milling
techniques have been recorded. This short review discusses the circumstances that
led this renaissance, highlighting the present intense interest in so-called green
chemistry, the enabling capacity of mechanochemistry to handle insoluble substrates,
and the identification of the profound influence that additives can have on mechanochemically
activated reactions. The core of this account focuses on salient developments in synthetic
organic chemistry, especially in amino acid and peptide mechanosynthesis, the successful
employment of mechanochemical activation in combination with asymmetric organocatalysis,
the promising combination of mechanochemical activation with enzymatic and whole cell
biocatalysis, the remarkable achievement of multicomponent selective reactions via
complex, multistep reaction pathways, and the mechanosynthesis of representative heterocycles.
The final section comments on some pending tasks in the area, such as scaling-up of
milling processes to be of practical use in the chemical industry, the requirement
of easier and more efficient control of reaction parameters and monitoring devices,
and consequently the careful analysis of additional procedures for a proper understanding
of mechanochemical phenomena.
1 Introduction
2 Brief History of Mechanochemistry
3 Milling Equipment and Reaction Parameters
4 Attributes of Mechanochemistry That Propelled Its Present Renaissance
4.1 Enormous Attention Being Presently Paid to Sustainable Chemistry
4.2 Reduced Energy Consumption
4.3 Additive-Based Mechanochemistry
4.4 Handling of Insoluble Reactants
4.5 ‘Impossible’ Reactions That Are Successful by Milling
4.6 Successful Handling of Air- and Water-Sensitive Reagents by Ball Milling
5 Salient Developments in the Mechanochemical Activation of Synthetic Organic Chemistry
5.1 Amino Acid and Peptide Mechanosynthesis
5.2 Asymmetric Organic Synthesis and Asymmetric Organocatalysis under Ball-Milling
Conditions
5.3 Mechanoenzymology
5.4 Multicomponent Reactions Activated by Mechanochemistry
5.5 Mechanosynthesis of Heterocycles and Modification of Heterocycles
6 Future Directions
6.1 Scaling-Up Mechanochemical Protocols
6.2 Temperature-Controlled Mechanochemistry
6.3 Understanding Mechanochemical Transformations
6.4 Emerging Mechanochemical Techniques
7 Conclusions
Key words
green chemistry - mechanochemistry - solid-state synthesis - synthetic organic chemistry
- mechanoenzymology - sustainable chemistry - ball milling
