1
74
Z.A. Bredikhina et al. / Journal of Molecular Structure 936 (2009) 171–176
0
.5%. Therefore it is a good but not definite diagnostic for conglom-
can easily be assigned to the ionic nature of the substance under
erate nature of this substance.
investigation. As a result of ionic associates formation, the thermo-
dynamic of stereoisomers melt mixing could noticeably deviate
from the ideal mixture model. Therein lies a little deviation be-
tween the calculated (as a Schröder–Van Laar diagram legs cross
point) value for eutectic melting point (Teu = 135.0 °C) and the
3.2. Thermochemical investigations
f
The DSC results for melting of the set of 1ꢀHCl samples with pre-
experimental value of T = 136.8 °C. At the same time, the experi-
R
f
determined composition were used in order to evaluate melting
mental Teu ꢃ 136.8 °C (black circles in Fig. 2), that is close to T ,
R
f
f
point T and enthalpy of fusion
D
H of racemic (subscript R) and
could easily be traced up to 70% ee samples, which is typical for
conglomerate forming substances.
scal-1ꢀHCl (subscript A) specimens, and to calculate the entropy
m
l
of mixing for enantiomeric 1ꢀHCl in the liquid state
D
S
and the
0
free energy of formation
D
G
of racemic compound in the solid
3.3. X-ray single crystal analysis
state. Table 2 represents experimental and calculated thermody-
namic parameters for bevantolol hydrochloride.
Bevantolol hydrochloride crystallizes in the triclinic P1 unit cell
having Z = 1, with the symmetry independent cell part consisting
of two molecular subunits A and B. Both of these molecules have
chiral centers on C2A and C2B carbons of the same absolute config-
uration (Fig. 3). They also have the same conformation, as is clear
from Fig. 4.
The only essential difference between the molecules consists in
the different nature of the nitrogen atoms: a protonated quater-
nary centre in the A molecule and a free amine in the B molecule.
At the same time, one of two chlorine atoms is present as an anion
in the unit cell, whereas the other one is a part of a free HCl mol-
ecule, with a H–Cl distance (dHCl) characterized by a value
1.60(11) Å.
ꢁ1
ꢁ1
The calculated entropy of mixing is equal to 5.01 J K mol
which is notably below the ideal value of 5.77 J K mol (Rln2)
,
ꢁ1
ꢁ1
for conglomerates. Nevertheless, as confirmed by our previous
m
experience, the
D
S
l
values calculated in a similar way for racemic
ꢁ
1
ꢁ1
compounds are usually substantially less than 5.0 J K mol . The
0
value of
D
G is negative but has a relatively small absolute value.
Therefore, both this characteristics are more likely indicative of a
conglomerate rather than of a racemic compound formation.
From the DSC data for the samples of different enantiomeric
purity, the melting temperature vs. composition diagram (binary
phase diagram) was drawn and is depicted in Fig. 2.
Experimental liquidus points (blue circles in Fig. 2) form an
apparent single eutectic V-shape curve (blue solid line) typical
for a racemic conglomerate [2]. Fig. 2 presents also the theoretical
liquidus curve (dashed line) deduced for a conglomerate from the
simplified Schröder–Van Laar equation [2]. Both experimental and
theoretical sets correlate quite well and some minor discrepancies
The presence of a free hydrogen chloride molecule in the pres-
ence of a free amine group in the crystal seems to be surprising at
the first glance, however, careful inspection of the Cambridge
Structural Database (CSD version 5.30, updates November 2008)
for the free HCl units reveals 150 hits. Among these structures, only
1
5
11 hits from the initial set have 3D information available, and for
7 hits only the H–Cl distance could be possible to obtain. This last
Table 2
f
f
set was inspected with the scrutiny. It turned out that the value of
HCl is rather sensitive to the nature of the crystal forming matrix.
DSC measured melting point T and enthalpy of fusion
DH of racemic (subscript R)
d
and highly enantioenriched 1ꢀHCl (subscript A) as well as calculated thermodynamic
characteristics for this compound.
It is relatively short for the neutral molecules such as toluene (in a
toluene dihydrochloride; CSD refcode LAKWUP, dHCl = 1.006 Å),
Parameter
Value
phenol
d
d
(HYQHCL01,
HCl = 1.104 Å, and JUFFAR, dHCl = 1.184 Å), mesitylene (LAKXAW,
HCl = 1.140 Å). For nitrogen containing substances, short dHCl is a
d
HCl = 1.061 Å),
2-butyne
(JUFDUJ,
f
T
T
A
R
(°C)
155.0
136.8
50.31
46.27
218
f
(°C)
f
ꢁ1
ꢁ1
D
D
D
D
H
A
(kJ mol
)
)
f
H
G
S
R
(kJ mol
characteristic feature of quaternary nitrogen compounds. For in-
stance, the mean value of dHCl is equal to 1.256, 1.267, and
0
ꢁ1
(J mol )
m
ꢁ1
ꢁ1
l
(J K mol
)
5.01
1
.115 Å for pyridinium chloride mono(hydrochloride), tris(hydro-
chloride), and pentakis(hydrochloride) (FOXMEK10, JAVFOB, and
JAVFUR), respectively.
For the set of substances where the number of nitrogen (as well
as phosphorus or arsenic) centers is more or equal to the number
of HCl units (25 compounds [20], 34 entries), the dHCl values vary
over the range from 1.049 and 1.143 Å (GEKXEZ and HAYPUT) to
1
.694 and 1.778 Å (LEKBEB and CUNWAJ). The mean value for
the whole array is d = 1.447 Å, = 0.183 Å. Therefore our result
m
r
m
showing dHCl = 1.60(11) Å is quite consistent with the d + r values
for the group of analogous compounds in question.
The coexistence of the amino and hydroxyl groups in the mole-
cules leads to the development of the elaborate system of hydro-
gen bonds in the crystals of bevantolol hydrochloride, with the
chlorine units acting as hydrogen bond acceptors. Thus the chlo-
rine anion Cl1 acts as an acceptor in four interactions bringing to-
gether four different molecules in two mutually orthogonal
directions, namely along the crystallographic 0a and 0b axes. At
the same time, chlorine atom Cl2 (part of HCl molecule) brings to-
gether only two molecules (A and B) along the crystallographic 0b
axis (Fig. 5). The quantitative interactions parameters are listed in
Table 3.
Thus arising hydrogen bond network leads to formation of 2D
supramolecular structures in the crystal – layers which are parallel
Fig. 2. Experimental (circles and solid lines) and calculated (dashed line) binary
melting phase diagram for bevantolol hydrochloride 1ꢀHCl.