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S. Matsumoto and J. Hwang
p-Cl derivative has been reported as a disappearing polymorph (Dunitz and Bernstein 1995). The thermally stable forms for the p-Cl and o-Br derivative are the Yand RO-forms, respectively. The crystal structures of both are characterised by close
packing, and the halogen substituents have no notable energy impact. In the metastable forms of the p-Cl derivative, weak intermolecular interactions involving Cl
atoms have been recognised to play an important role in the molecular arrangement.
For the o-Br derivatives, various Br-related interactions, such as Br–N and Br–Br,
have been observed in their crystal structures.
This example clearly indicates that weak halogen interactions with respect to Cl
and Br atoms have an impact on structural variation in a crystalline state.
6.3 Examples of Coloured Organic Compounds
6.3.1 ROY (QAXMEH)
5-Methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile (QAXMEH), known as
ROY, is an organic compound synthesised as an intermediate for the development of
a novel compound with antipsychotic activity (Calligaro et al. 1997). This compound
is coloured, although it is not categorised as a dye because of its weak light absorption
in the visible region. ROY is known as the organic small molecule whose polymorphic forms have been the most extensively structurally analysed, where all forms can
be obtained under ambient conditions and many can also be crystallised concomitantly (Yu et al. 2000; Yu 2010). In addition to the seven polymorphic forms analysed
by single-crystal measurements, three polymorphic forms have been characterised in
the form of thin films (Yu 2010; Chen et al. 2005). Among the seven analysed polymorphic forms, five are stable and two are meta-stable under ambient conditions. The
three film forms have been reported to be unstable, instead of transforming to other
forms within hours to days (Yu 2010). This polymorphic system is representative of
conformational polymorphs (Cruz-Cabeza and Bernstein 2014).
Figure 6.14 shows the molecular conformations of the seven forms of ROY—Y,
ON, OP, R, YN, ORP and YT04—and Table 6.6 lists their crystallographic parameters. The abbreviations denote their crystal appearance, such as ‘orange needles’ for
ON. As shown in the figure, the conformational differences in the seven forms are
related to the torsion angle between the phenyl and thiophene rings. Several forms
also have a relatively small twist between the phenyl ring and nitro moiety. The
torsion angle seems to be related to the crystal colour, indicating that the colours
of the polymorphs are dependent on the electronic state of the molecules in the
crystal (Yu 2002). Meanwhile, no significant differences have been observed in the
molecular bond lengths or angles of the different polymorphs (Yu 2010).
ROY has been reported to form intramolecular hydrogen bonds between the amino
and nitro groups in its crystal forms. The molecular arrangements are thus considered
to form mainly by van der Waals interactions and weak hydrogen bonding (Yu 2010;
S. Matsumoto and J. Hwang
p-Cl derivative has been reported as a disappearing polymorph (Dunitz and Bernstein 1995). The thermally stable forms for the p-Cl and o-Br derivative are the Yand RO-forms, respectively. The crystal structures of both are characterised by close
packing, and the halogen substituents have no notable energy impact. In the metastable forms of the p-Cl derivative, weak intermolecular interactions involving Cl
atoms have been recognised to play an important role in the molecular arrangement.
For the o-Br derivatives, various Br-related interactions, such as Br–N and Br–Br,
have been observed in their crystal structures.
This example clearly indicates that weak halogen interactions with respect to Cl
and Br atoms have an impact on structural variation in a crystalline state.
6.3 Examples of Coloured Organic Compounds
6.3.1 ROY (QAXMEH)
5-Methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile (QAXMEH), known as
ROY, is an organic compound synthesised as an intermediate for the development of
a novel compound with antipsychotic activity (Calligaro et al. 1997). This compound
is coloured, although it is not categorised as a dye because of its weak light absorption
in the visible region. ROY is known as the organic small molecule whose polymorphic forms have been the most extensively structurally analysed, where all forms can
be obtained under ambient conditions and many can also be crystallised concomitantly (Yu et al. 2000; Yu 2010). In addition to the seven polymorphic forms analysed
by single-crystal measurements, three polymorphic forms have been characterised in
the form of thin films (Yu 2010; Chen et al. 2005). Among the seven analysed polymorphic forms, five are stable and two are meta-stable under ambient conditions. The
three film forms have been reported to be unstable, instead of transforming to other
forms within hours to days (Yu 2010). This polymorphic system is representative of
conformational polymorphs (Cruz-Cabeza and Bernstein 2014).
Figure 6.14 shows the molecular conformations of the seven forms of ROY—Y,
ON, OP, R, YN, ORP and YT04—and Table 6.6 lists their crystallographic parameters. The abbreviations denote their crystal appearance, such as ‘orange needles’ for
ON. As shown in the figure, the conformational differences in the seven forms are
related to the torsion angle between the phenyl and thiophene rings. Several forms
also have a relatively small twist between the phenyl ring and nitro moiety. The
torsion angle seems to be related to the crystal colour, indicating that the colours
of the polymorphs are dependent on the electronic state of the molecules in the
crystal (Yu 2002). Meanwhile, no significant differences have been observed in the
molecular bond lengths or angles of the different polymorphs (Yu 2010).
ROY has been reported to form intramolecular hydrogen bonds between the amino
and nitro groups in its crystal forms. The molecular arrangements are thus considered
to form mainly by van der Waals interactions and weak hydrogen bonding (Yu 2010;