426
R. Tamura et al.
Fig. 20.19 Preferential
enrichment experiment of
cocrystal 4 using an 8-fold
supersaturated H 2 O-EtOH
(1:1 v/v) solution.
Conditions: a H 2 O-EtOH
(8.8 mL) at 5 °C for 6 days,
b H 2 O-EtOH, (7.9 mL) at
5 °C for 4 days, c H 2 O-EtOH
(7.1 mL) at 5 °C for 5 days,
d H 2 O-EtOH (6.6 mL) at
5 °C for 4 days, e removal of
the solvent by evaporation.
Data cited from Ref. [37]
polymorphic transition was not observed during crystallization by in situ ATR-FTIR
spectroscopy, TC video-microscopy, and in situ time-resolved XRPD measurement.
Therefore, in this case, a direct nucleation (phase transition) from the molecular
clusters present in the supersaturated solution giving mixed crystals is most likely
to induce the chiral symmetry breaking and thereby PE. The crystal structure of the
stable racemic cocrystal 4 is shown in Fig. 20.20.
Furthermore, in this PE experiment, a total amount of two enantiomers dissolved in
the mother liquor was kept constant despite the increasing ee value of one enantiomer
in the mother liquor during crystallization, in contrast to the case of the first generation
of organic salts [32]. More interestingly, by adding a minute amount (0.1 wt % of the
Fig. 20.20 Crystal structure
of DL-cocrystal 4. Data cited
from Ref. [37]
R. Tamura et al.
Fig. 20.19 Preferential
enrichment experiment of
cocrystal 4 using an 8-fold
supersaturated H 2 O-EtOH
(1:1 v/v) solution.
Conditions: a H 2 O-EtOH
(8.8 mL) at 5 °C for 6 days,
b H 2 O-EtOH, (7.9 mL) at
5 °C for 4 days, c H 2 O-EtOH
(7.1 mL) at 5 °C for 5 days,
d H 2 O-EtOH (6.6 mL) at
5 °C for 4 days, e removal of
the solvent by evaporation.
Data cited from Ref. [37]
polymorphic transition was not observed during crystallization by in situ ATR-FTIR
spectroscopy, TC video-microscopy, and in situ time-resolved XRPD measurement.
Therefore, in this case, a direct nucleation (phase transition) from the molecular
clusters present in the supersaturated solution giving mixed crystals is most likely
to induce the chiral symmetry breaking and thereby PE. The crystal structure of the
stable racemic cocrystal 4 is shown in Fig. 20.20.
Furthermore, in this PE experiment, a total amount of two enantiomers dissolved in
the mother liquor was kept constant despite the increasing ee value of one enantiomer
in the mother liquor during crystallization, in contrast to the case of the first generation
of organic salts [32]. More interestingly, by adding a minute amount (0.1 wt % of the
Fig. 20.20 Crystal structure
of DL-cocrystal 4. Data cited
from Ref. [37]