The effect of milling frequency on a mechanochemical organic reaction monitored by in situ Raman spectroscopy

Abstract

We provide the first in situ and real-time study of the effect of milling frequency on the course of a mechanochemical organic reaction conducted using a vibratory shaker (mixer) ball mill. The use of in situ Raman spectroscopy for real-time monitoring of the mechanochemical synthesis of a 2,3-diphenylquinoxaline derivative revealed a pronounced dependence of chemical reactivity on small variations in milling frequency. In particular, in situ measurements revealed the establishment of two different regimes of reaction kinetics at different frequencies, providing tentative insight into processes of mechanical activation in organic mechanochemical synthesis.

Mechanoenzymatic Breakdown of Chitinous Material to N‐Acetylglucosamine: The Benefits of a Solventless Environment

“…Interestingly, more enzyme did not necessarily translate into a higher yield (Figure B), and a chitinase loading of 0.7 % ( w / w ) was optimal. Finally, milling frequencies of 10, 20, and 30 Hz all gave similar enzyme activity, but a higher reproducibility was observed at 30 Hz (Figure S2 D in the Supporting Information) …”

“…Finally,m illing frequencies of 10, 20, and3 0Hza ll gave similar enzyme activity,b ut ah igherr eproducibility was observed at 30 Hz ( Figure S2 Di nt he SupportingI nformation). [58] Beforei nvestigating the reactivity upon RAging, we also examined enzyme kinetics in as imple combination of one-time LAG followed by aging. As shown in Figure2C, increasing LAG time beyond5min did not substantially increase the yield of reducings ugars.…”

In Situ Investigations of Mechanochemical One‐Pot Syntheses

“…Ac omparison of the thermal sequences for the possible analytical in situ combinations revealed no significant differences.Therefore,any contribution of radiation heat to the temperature profile can be excluded. [13] Thei nsitu data for the cocrystal formation of theobromine (tb) with oxalic acid (ox) dihydrate (2:1) at 30 Hz for 20 min is presented in Figure S3. Theo bserved temperatures are comparable to those reported in ex situ measurements.…”

Recent Advances in Mechanochemical Organic Synthesis

“…Since the introduction of real-time in situ techniques for monitoring mechanochemical reactions [92], based on synchrotron PXRD, Raman spectroscopy, and their combination, mechanistic details for a number of organic transformations, metalorganic framework (MOF) systems, and solid-state cocrystallizations have been studied and revealed [96]. These in situ studies also allow for kinetic considerations of solid-state milling reactions under LAG conditions [97], as well as investigations of the effect of milling parameters such as frequency [98], number of milling balls [99], or the ball to reactant ratio on the course of mechanochemical reactions [100]. On a technical side, such investigations go hand in hand with the development of equipment necessary to conduct them.…”