(737f) Fast Temperature Cycling via Microwave Heating Enables Enhanced Deracemization

Fast Temperature Cycling via Microwave Heating
Enables Enhanced Deracemization

Christos
Xiouras¹, Fabio Cameli¹,
and Georgios D. Stefanidis¹

¹ Process
Engineering for Sustainable Systems, Department of Chemical Engineering, KU
Leuven, Belgium;

Keywords:
Deracemization, Crystallization, Temperature Cycling,
Viedma ripening; Microwave Heating;

In
2005, Viedma [1] demonstrated a remarkable non-classical crystallization
phenomenon according to which an initially racemic crystal population converts
to a single chirality upon grinding the crystals in their saturated solution.
The process was initially demonstrated for the achiral NaClO₃ which
crystallizes as chiral crystals, but was later extended to intrinsically chiral
compounds that crystallize as conglomerates (i.e. each individual
crystal contains a single enantiomer) [2]. The underlying mechanisms of the phenomenon
are still under discussion, but the process is considered to have high
potential for application in the pharmaceutical industry, where separation of
enantiomers is often required. However, the application of grinding at a larger
industrial scale is rather complicated and could lead to problems in downstream
processing. Recently, it was discovered that grinding could be replaced by periodic
temperature fluctuations (temperature cycling), which is more convenient at a
larger scale [3].

In
contrast to conventional heating, which is slow and requires a heat transfer
surface, microwave heating is rapid and volumetric in nature. Therefore, if combined
with fast cooling, microwave activation can enable novel process operating
windows for temperature cycling as compared to conventional heating. Figure 1
(left) shows that the application of such operation for the model system
glutamic acid leads to an order of magnitude faster heating and cooling rates
compared to conventional operation, which in turn leads to significant
reduction in the total deracemization time required (Figure 2, right). Besides
intensification of the deracemization process, the extreme operating windows
applied here also lead to new insights into the obscure driving mechanisms of
solid-state deracemization phenomena. 

Figure
1.
Left: Temperature profile using microwave heating (red dashed line) and
conventional heating (black line). Right: Evolution of solid phase enantiomeric
excess for in time in: microwave reactor (black points) and conventional
heating configuration (red points). Model system: glutamic acid conglomerate
crystals in acetic acid and catalytic salicylaldehyde.

References

[1]
C. Viedma; Chiral Symmetry Breaking During Crystallization: Complete Chiral
Purity Induced by Nonlinear Autocatalysis and Recycling Phys. Rev. Lett.
94 (2005), 3−6

[2]
W.L. Noorduin, T. Izumi, A. Millemaggi, M. Leeman, H. Meekes, W.J.P. Van
Enckevort, R.M. Kellogg, B. Kaptein, E. Vlieg, D.G. Blackmond, Emergence of a
single solid chiral state from a nearly racemic amino acid derivative, J.
Am. Chem. Soc., 130 (2008), 1158-1159.

[3]
K. Suwannasang, A. E. Flood., C. Rougeot, & G. Coquerel. Using programmed
heating–cooling cycles with racemization in solution for complete symmetry
breaking of a conglomerate forming system. Cryst. Growth Des., 13 (2013),
3498-3504.