Amino Acids and Peptides in Ball Milling - Ball Milling Towards Green Synthesis: Applications, Projects, Challenges - page 148

This approach is advantageous in that it enables the production of di-
peptide avoiding the use of pre-activated a-amino acids as substrates.
Nevertheless, this particularity may be useful only in the very limited num-
ber of cases where the pre-activated a-amino ester is hardly synthesizable or
not commercially available. Besides, the approach developed by Margeti ´
and coworkers still requires the use of 2 equivalents of the highly toxic or-
ganic base DMAP. In addition, one can regret the use of an explosive liquid
as grinding assistant such as nitromethane, which unfortunately hampers
the environmental impact of the process.
In contrast, a very interesting point in this approach is that the peptide
recovery is realized in the absence of any organic solvent. Organic solvent-
free recovery and purification have been a scarcely studied theme in fine
organic chemistry, but promising methods have been published re-
cently. 38,40,48-51 Mechanochemical peptide syntheses would gain even more
interest in the organic chemist's community if solutions addressing this
challenge would emerge.

6.4 Conclusion
Performing a reaction in a ball-mill is an ecient way of reaching more
sustainable conditions in organic synthesis, especially if combined with
innocuous solvent-assisted grinding and organic solvent-free recovery or
purification. These approaches were highlighted in this chapter, demon-
strating that amino acid derivatization or protection and peptide synthesis
could greatly benefit from such processes.

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