(579e) Liquid−Liquid Phase Separation during the Cooling Crystallization of Pyraclostrobin

Liquid−Liquid
Phase Separation during the Cooling Crystallization of Pyraclostrobin

Crystallization,
as a method of isolation and purification, is widely used in fine chemicals,
food and pharmaceutical industries. It is a powerful mean to improve the properties
of particle, such as changing crystal form, narrowing crystal size distribution
(CSD), modifying crystal habit and so on. However, sometimes
droplets like oil drops are generated instead of crystals are appeared from the
supersaturated solution during the cooling and/or solventing-out
crystallization process. This phenomenon is always termed as liquid¨Cliquid demixing, liquid¨Cliquid-phase separation (LLPS) or oiling
out.

The
main purpose of this investigation was to investigate the cooling
crystallization process of pyraclostrobin in
isopropanol/cyclohexane solvent mixtures. It was found that liquid−liquid phase
separation will occurred under some certain conditions. In order to understand
the mechanism of the liquid−liquid separation and the influence of cooling rate
on oiling out, the phase diagram and cloud point curves at different cooling
rate were experimentally measured with the aid of in situ tools, such as PVM,
FBRM, ATR-FTIR and Raman. The phase diagram includes the solubility curve, the
liquid−liquid separation curve, supersolubility
curves, and clear point. It was found from the phase diagram that a normal single-phase
crystallization would change to a oiling-out crystallization once the
concentration of pyraclostrobin exceeded a certain
value during crystallization. Contrasting with cloud point curves of different
cooling rate, it is obvious that the cooling rate has a significant effect on
the metastable state critical oiling out point. The concentration corresponds
to the metastable state for critical oiling out point decreases with the
increase of cooling rate. In the cooling and heating cyclic process, the
solution has experienced five stages. During cooling down the solution from
high temperature, oiling out including stable LLPS and metastable LLPS occurred,
then nucleation and growth of crystals happened; upon heating up, the crystals dissolved
gradually, then the solution with a small amount of particles transformed into transient
oil phase and finally it formed a stable and clear solution.

Considering
the crystal properties of final products, some experiments designed to
investigate the influence of cooling rate and initial concentration. And the
result showed that the higher cooling rates, the more serious agglomeration and
poorer crystal habit of final products would get. Another result is that
initial concentration has little influence on the crystal properties. High
quality of products can be obtained by designing route of cooling
crystallization according to the phase diagram.

Figures

Figure 1 Phase diagram of pyraclostrobin in 10 wt % isopropanol/cyclohexane
solvent mixtures.

Figure 2 SEM images of pyraclostrobin product obtained from different experiments

a
refer to pyraclostrobin products at the cooling rate
of 0.1 K/min under concentration of 10g/100g solvent; b refer to pyraclostrobin products at the cooling rate of 0.5 K/min
under concentration of 10g/100g solvent; c refer to pyraclostrobin products at the cooling rate of 0.1 K/min
under concentration of 15g/100g solvent; d refer to pyraclostrobin products at the cooling rate of 0.5 K/min
under concentration of 15g/100g solvent.