424
R. Tamura et al.
20.5.2 Leucine-Oxalic Acid Cocrystal (3) [36]
Although the 1:1 cocrystal (3) of DL-Leu and oxalic acid has a eutectic ee value
as high as >98% in H 2 O–EtOH (v/v 2:1) at 25 °C, only modest PE phenomenon
was observed even when successive crystallization was performed from a slightly
enantiomerically enriched (5.0% ee) fivefold supersaturated solution at 5 °C [36]
(Fig. 20.17).
Interestingly, the crystal structure of the stable DL-3 was quite different from
those of the first generation of organic salts and DL-2, although the space group
was P–1. Namely, the crystal structure was composed of a pair of 2D D and L
sheets (Fig. 20.18a, b). Accordingly, the mechanism of PE was different from the
previous ones. A new mechanism consistent with all the experimental data was
proposed to involve the following processes in the case of using a slightly L-rich
sample: (1) preferential formation of homochiral 1D D and L chains of Leu through
the intermediary of oxalic acid in the supersaturated solution, (2) direct nucleation
(phase transition) from the slightly L-rich molecular cluster to give the stable, slightly
L-rich mixed crystalline phase composed of 2D D and L sheets (Fig. 20.18c), and
(3) preferential redissolution of the L sheets from the area of irregular and brittle
sheets packing in the crystals, in which an even number of L sheets (four sheets in
this case) are surrounded by two D sheets, into the mother liquor until the deposited
crystals are slightly enriched with the opposite D enantiomer (Fig. 20.18c). Thus,
the ee value in the mother liquor cannot increase largely, because the ee value of the
resulting D-rich deposited crystals is as low as less than 1.0%.
Fig. 20.17 Preferential enrichment experiment of cocrystal 3 by using a fivefold supersaturated
solution in H 2 O/EtOH (2/1 v/v), compared with the solubility at 25 °C (Table 1). Conditions:
a H 2 O/EtOH (2/1 v/v) (2.0 mL) at 5 °C for 7days. b H 2 O/EtOH (2/1 v/v) (1.6 mL) at 5 °C for 4
days. c H 2 O/EtOH (2/1 v/v) (1.5 mL) at 5 °C for 5 days. d H 2 O/EtOH (2/1 v/v) (1.3 mL) at 5 °C
for 4 days. e Removal of the solvent by evaporation. Data cited from Ref. [36]
R. Tamura et al.
20.5.2 Leucine-Oxalic Acid Cocrystal (3) [36]
Although the 1:1 cocrystal (3) of DL-Leu and oxalic acid has a eutectic ee value
as high as >98% in H 2 O–EtOH (v/v 2:1) at 25 °C, only modest PE phenomenon
was observed even when successive crystallization was performed from a slightly
enantiomerically enriched (5.0% ee) fivefold supersaturated solution at 5 °C [36]
(Fig. 20.17).
Interestingly, the crystal structure of the stable DL-3 was quite different from
those of the first generation of organic salts and DL-2, although the space group
was P–1. Namely, the crystal structure was composed of a pair of 2D D and L
sheets (Fig. 20.18a, b). Accordingly, the mechanism of PE was different from the
previous ones. A new mechanism consistent with all the experimental data was
proposed to involve the following processes in the case of using a slightly L-rich
sample: (1) preferential formation of homochiral 1D D and L chains of Leu through
the intermediary of oxalic acid in the supersaturated solution, (2) direct nucleation
(phase transition) from the slightly L-rich molecular cluster to give the stable, slightly
L-rich mixed crystalline phase composed of 2D D and L sheets (Fig. 20.18c), and
(3) preferential redissolution of the L sheets from the area of irregular and brittle
sheets packing in the crystals, in which an even number of L sheets (four sheets in
this case) are surrounded by two D sheets, into the mother liquor until the deposited
crystals are slightly enriched with the opposite D enantiomer (Fig. 20.18c). Thus,
the ee value in the mother liquor cannot increase largely, because the ee value of the
resulting D-rich deposited crystals is as low as less than 1.0%.
Fig. 20.17 Preferential enrichment experiment of cocrystal 3 by using a fivefold supersaturated
solution in H 2 O/EtOH (2/1 v/v), compared with the solubility at 25 °C (Table 1). Conditions:
a H 2 O/EtOH (2/1 v/v) (2.0 mL) at 5 °C for 7days. b H 2 O/EtOH (2/1 v/v) (1.6 mL) at 5 °C for 4
days. c H 2 O/EtOH (2/1 v/v) (1.5 mL) at 5 °C for 5 days. d H 2 O/EtOH (2/1 v/v) (1.3 mL) at 5 °C
for 4 days. e Removal of the solvent by evaporation. Data cited from Ref. [36]