Monoclinic and ortho-rhom-bic polymorphs of 4,4′,6,6′-tetra- chloro-2,2′-(piperazine-1,4-diyldimethylene)diphenol

Article abstract of DOI:10.1107/S0108270107035408

The title compound, C18H18Cl4N2O2, crystallizes as monoclinic and ortho-rhom-bic polymorphs from CHCl3-CH3OH solution. In both polymorphic forms, the mol-ecule lies on a crystallographic centre of inversion (at the piperazine ring centroid) and exhibits a

Full text of DOI:10.1107/S0108270107035408

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
(Wardell et al., 2007; Li et al., 2006). We report here the
molecular and supramolecular structures of polymorphs (I)
and (II)
ISSN 0108-2701
Monoclinic and orthorhombic poly-
morphs of 4,40,6,60-tetrachloro-2,20-
(piperazine-1,4-diyldimethylene)-
diphenol
Koji Kubono* and Kunihiko Yokoi
The molecular structures of polymorphs (I) and (II) are
shown in Figs. 1 and 2, respectively. In both polymorphic
forms, the molecule lies on a centre of inversion at the
piperazine ring centroid. The bond lengths and angles in (I)
and (II) are similar, and agree with the values in both the
p-cresol derivative (Kuppayee et al., 1999) and the 5-bromo-
salicylaldehyde system (Thirumurugan et al., 1998). In both (I)
and (II), the piperazine rings adopt a chair conformation. The
molecular structures of (I) and (II) are very similar, and thus
only small differences are observed. The largest differences in
bond distances and angles between the two polymorphs are
Division of Natural Science, Osaka Kyoiku University, Kashiwara, Osaka 582-8582,
Japan
Correspondence e-mail: kubono@cc.osaka-kyoiku.ac.jp
Received 13 June 2007
Accepted 19 July 2007
Online 17 August 2007
The title compound, C18H18Cl4N2O2, crystallizes as monoclinic
and orthorhombic polymorphs from CHCl3±CH3OH solution.
In both polymorphic forms, the molecule lies on a crystal-
lographic centre of inversion (at the piperazine ring centroid)
and exhibits an intramolecular OÐHÁ Á ÁN hydrogen bond. In
the monoclinic polymorph (space group P21/c), the molecules
are linked by intermolecular CÐHÁ Á ÁCl hydrogen bonds into
a ribbon sheet built from R88(34) rings. In the orthorhombic
polymorph (space group Pbcn), the molecules are linked by
intermolecular CÐHÁ Á ÁO hydrogen bonds into a ribbon sheet
of R66(34) rings. The sheets in the orthorhombic polymorph are
crosslinked into a three-dimensional framework by ꢀ±ꢀ
stacking interactions.
Ê
Ê
Ê
less than 0.02 A [O1ÐC11 = 1.343 (2) A in (I) and 1.358 (3) A
in (II)] and less than 2ꢀ [O1ÐC1ÐC6 = 122.56 (19)ꢀ in (I) and
121.4 (2)ꢀ in (II)], respectively. The greatest differences are for
the torsion angles involving atoms C6 and C7, viz. C5ÐC6Ð
C7ÐN1 [ 143.7 (2)ꢀ in (I) and 146.7 (2)ꢀ in (II)] (Tables 1
and 3). The differences are re¯ected in the orientation of the
Comment
The design and synthesis of piperidine and piperazine deri-
vatives are of interest in pharmacology (Geng et al., 2002;
Favor et al., 2007). In addition, derivatives with phenol or
pyridine arms can act as complexing reagents with metal ions
(Chi et al., 2002; Okamatsu et al., 2007). Recently, we reported
the crystal structure of the piperidine compound 2,4-dichloro-
6-(piperidin-1-ylmethyl)phenol (HClbpipe) (Kubono et al.,
2005). In the supramolecular structure, intermolecular CÁ Á ÁC
and ClÁ Á ÁCl contacts are observed (Kubono et al., 2005);
however, in the crystal structure of the CuII complex of
HClbpipe, viz. Cu(Clbpipe)2, there are no signi®cant inter-
molecular interactions (Kubono et al., 2006). Therefore, we
designed and synthesized the new supramolecular tetra-
dentate ligand 4,40,6,60-tetrachloro-2,20-(piperazine-1,4-diyldi-
methylene)diphenol (H2Cl2bpi), consisting of two dichloro-
phenol arms and a piperazine ring. H2Cl2bpi crystallizes in
monoclinic, (I), and orthorhombic, (II), polymorphic forms
from CHCl3±CH3OH solution. There are numerous recent
studies on polymorphism in drugs (Gelbrich et al., 2007;
Drebushchak et al., 2007) and supramolecular compounds
Figure 1
A view of polymorph (I), showing the atom-labelling scheme and
displacement ellipsoids drawn at the 50% probability level. H atoms are
represented by circles of arbitrary size. [Symmetry code: (i) 1 x, y,
1
z.]
Figure 2
A view of polymorph (II), showing the atom-labelling scheme and
displacement ellipsoids drawn at the 50% probability level. H atoms are
represented by circles of arbitrary size. [Symmetry code: (ii) 2 x, y,
1
z.]
Acta Cryst. (2007). C63, o535±o537
DOI: 10.1107/S0108270107035408
# 2007 International Union of Crystallography o535

organic compounds
aryl rings with respect to the central piperazine rings. The
dihedral angles between the mean planes of the piperazine
ring and the aryl rings are slightly different in the two poly-
morphs, viz. 101.28 (10)ꢀ in (I) and 104.00 (9)ꢀ in (II). The
intramolecular O1ÐH1Á Á ÁN1 hydrogen-bond distances in (I)
(Bernstein et al., 1995) chain running parallel to the [101]
direction and generated by the c-glide plane at y = 0.25. A
v
Ê
weak intermolecular CÁ Á ÁC contact [C2Á Á ÁC4 = 3.581 (5) A;
1
2
1
symmetry code: (v) x,
y,
+ z] is also observed. The
2
molecules are linked by the C(6) chains and CÁ Á ÁC contacts
into a (100) ribbon sheet of R88(34) rings (Fig. 3). In addition,
there is a weak intermolecular CÐHÁ Á ÁCl contact [H9Á Á Á
Ê
and (II) are 2.700 (2) and 2.660 (2) A, respectively (Tables 2
and 4).
Cl1vi = 2.962 A; symmetry code: (vi) 1 + x, y, z] between
Ê
In the crystal structure of polymorph (I), there is an inter-
molecular CÐHÁ Á ÁCl hydrogen bond (Table 1). Atom C7 in
the molecule at (x, y, z) acts as a hydrogen-bond donor to
adjacent sheets.
In the crystal structure of polymorph (II), there is an
intermolecular CÐHÁ Á ÁO hydrogen bond (Table 2). Atom C3
in the molecule at (x, y, z) acts as a hydrogen-bond donor to
1
2
1
atom Cl2 in the molecule at (x,
y, + z), forming a C(6)
2
1
atom O1 in the molecule at (32 x, + y, z), forming a C(5)
2
chain running parallel to the [010] direction and generated by
the b-glide plane at x = 0.75. The molecules are linked by the
C(5) chains into a (001) ribbon sheet of R66(34) rings (Fig. 4).
The sheets are crosslinked into a three-dimensional frame-
work by ꢀÁ Á Áꢀ interactions [C1Á Á ÁC1vii = 3.528 (3) A, C2Á Á Á
Ê
vii
C5vii = 3.564 (3) A and C3Á Á ÁC4 = 3.427 (3) A; symmetry
Ê
Ê
3
2
code: (vii) 1 + x, y,
z].
Each polymorph is characterized by the supramolecular
interactions: for (I), CÐHÁ Á ÁCl hydrogen bonds and weak
CÁ Á ÁC contacts, and for (II), CÐHÁ Á ÁO hydrogen bonds and
ꢀÁ Á Áꢀ interactions. There are no short ClÁ Á ÁCl interactions in
either polymorph.
Experimental
A mixture of 2,4-dichlorophenol (13.04 g, 80 mmol), piperazine
(3.45 g, 40 mmol) and paraformaldehyde (2.40 g, 80 mmol) in
methanol (60 ml) was re¯uxed for 6 h. The mixture was cooled to
room temperature and the solvent evaporated under vacuum. The
product was recrystallized from CHCl3±CH3OH to give colourless
crystals suitable for X-ray analysis. Visual examination of the crystals
under a microscope showed that most of them consisted of (I), with a
small amount of (II). By crystallizing H2Cl2bpi under various
conditions, we attempted to obtain extra amounts of (II); however, no
remarkable improvement was observed. Samples of the two poly-
morphs were isolated manually [yield 10.40 g (59.6%); m.p. 510.0±
512.1 K for (I) and 510.4±512.8 K for (II)]. Phase transitions of one
polymorph into another were not observed by differential scanning
calorimetry (DSC). Analysis calculated for C18H18Cl4N2O2: C 49.57,
H 4.16, N 6.42%; found: C 49.54, H 4.20, N 6.46%. 1H NMR (CDCl3,
p.p.m., 400 MHz): ꢁ 2.66 (brs, 8H, CH2), 3.72 (s, 4H, CH2), 6.90 (d, J =
2.4 Hz, 2H, ArH), 7.28 (d, J = 2.4 Hz, 2H, ArH), 11.2 (brs, 2H, OH).
Figure 3
A stereoview of part of the crystal structure of polymorph (I), showing
the formation of a centrosymmetric R88(34) ring. The OÐHÁ Á ÁN and CÐ
HÁ Á ÁCl hydrogen bonds are shown as dashed lines. For the sake of clarity,
H atoms not involved in the hydrogen bonds have been omitted.
Polymorph (I)
Crystal data
3
Ê
C18H18Cl4N2O2
Mr = 436.14
V = 958.7 (3) A
Z = 2
Monoclinic, P21=c
Mo Kꢃ radiation
ꢄ = 0.63 mm
T = 298 K
0.25 Â 0.15 Â 0.15 mm
1
Ê
a = 7.4861 (13) A
Ê
b = 17.2008 (13) A
Ê
c = 8.0283 (19) A
ꢂ = 111.972 (13)ꢀ
Data collection
Figure 4
A stereoview of part of the crystal structure of polymorph (II), showing
the formation of R66(34) rings. The OÐHÁ Á ÁN and CÐHÁ Á ÁO hydrogen
bonds are shown as dashed lines. For the sake of clarity, H atoms not
involved in the hydrogen bonds have been omitted.
Rigaku AFC-7R diffractometer
2364 measured re¯ections
2215 independent re¯ections
1526 re¯ections with F2 > 2ꢅ(F2)
Rint = 0.017
3 standard re¯ections
every 150 re¯ections
intensity decay: 0.1%
ꢁ
o536 Kubono and Yokoi C18H18Cl4N2O2 and C18H18Cl4N2O2
Acta Cryst. (2007). C63, o535±o537

organic compounds
Re®nement
Table 4
Hydrogen-bond geometry (A, ) for polymorph (II).
ꢀ
Ê
R[F2 > 2ꢅ(F2)] = 0.040
wR(F2) = 0.125
S = 1.01
127 parameters
H-atom parameters constrained
3
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
Ê
Áꢆmax = 0.68 e A
3
Ê
0.35 e A
1528 re¯ections
Áꢆmin
=
O1ÐH1Á Á ÁN1
0.84
0.95
1.89
2.48
2.660 (2)
3.347 (3)
151
152
C3ÐH2Á Á ÁO1iv
Table 1
Symmetry code: (iv) x ‡ 32; y ‡ 21; z.
Selected torsion angles (ꢀ) for polymorph (I).
C2ÐC1ÐC6ÐC7
C1ÐC6ÐC7ÐN1
177.8 (2)
39.8 (3)
C5ÐC6ÐC7ÐN1
C4ÐC5ÐC6ÐC7
143.7 (2)
176.1 (3)
For both polymorphs, data collection: WinAFC (Rigaku/MSC,
2006); cell re®nement: WinAFC; data reduction: CrystalStructure
(Rigaku/MSC, 2006); program(s) used to solve structure: SIR92
(Altomare et al., 1993); program(s) used to re®ne structure: CRYS-
TALS (Betteridge et al., 2003); molecular graphics: PLATON (Spek,
2003); software used to prepare material for publication: Crystal-
Structure.
Table 2
Hydrogen-bond geometry (A, ) for polymorph (I).
ꢀ
Ê
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
O1ÐH1Á Á ÁN1
0.85
0.95
1.97
2.78
2.700 (2)
3.688 (3)
145
159
C7ÐH4Á Á ÁCl2iii
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: GG3104). Services for accessing these data are
described at the back of the journal.
Symmetry code: (iii) x; y ‡ 12; z ‡ 21.
Polymorph (II)
References
Crystal data
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3
Ê
C18H18Cl4N2O2
Mr = 436.14
Orthorhombic, Pbcn
a = 10.360 (3) A
b = 12.1910 (17) A
Ê
c = 15.332 (5) A
V = 1936.4 (9) A
Z = 4
Mo Kꢃ radiation
1
Ê
ꢄ = 0.63 mm
T = 298 K
Ê
0.20 Â 0.15 Â 0.12 mm
Drebushchak, T. N., Chukanov, N. V. & Boldyreva, E. V. (2007). Acta Cryst.
C63, o355±o357.
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Data collection
Rigaku AFC-7R diffractometer
3228 measured re¯ections
2222 independent re¯ections
1922 re¯ections with F2 > 2ꢅ(F2)
Rint = 0.024
3 standard re¯ections
every 150 re¯ections
intensity decay: 0.3%
Geng, B., Fleming, P. R., Umlauf, S., Lin, A. & Pallai, P. V. (2002). Bioorg. Med.
Chem. Lett. 12, 775±778.
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o3706±o3708.
Kubono, K., Oshima, S., Hirayama, N. & Yokoi, K. (2006). Acta Cryst. E62,
m2858±m2859.
Re®nement
R[F2 > 2ꢅ(F2)] = 0.037
wR(F2) = 0.106
S = 1.00
127 parameters
H-atom parameters constrained
3
Ê
Áꢆmax = 0.46 e A
3
Ê
0.68 e A
1925 re¯ections
Áꢆmin
=
Kuppayee, M., Kumaran, D., Ponnuswamy, M. N., Kandaswamy, M., Violet,
M. J., Chinnakali, K. & Fun, H.-K. (1999). Acta Cryst. C55, 2147±2149.
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m872.
Table 3
Selected torsion angles (ꢀ) for polymorph (II).
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653.
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3.8.1). Rigaku/MSC, The Woodlands, Texas, USA.
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C2ÐC1ÐC6ÐC7
C1ÐC6ÐC7ÐN1
176.0 (2)
38.0 (3)
C5ÐC6ÐC7ÐN1
C4ÐC5ÐC6ÐC7
146.7 (2)
173.7 (2)
Thirumurugan, R., Shanmuga Sundara Raj, S., Shanmugam, G., Fun, H.-K.,
Chinnakali, K., Chantrapromma, S., Marappan, M. & Kandaswamy, M.
(1998). Acta Cryst. C54, 780±781.
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C. (2007). Acta Cryst. B63, 101±110.
For both polymorphs, the H atoms of the hydroxyl groups were
found from a difference Fourier map. The other H atoms were placed
Ê
at idealized positions, with CÐH = 0.95 A. All the H atoms were
re®ned as riding, with Uiso(H) = 1.2Ueq(C).
ꢁ
Acta Cryst. (2007). C63, o535±o537
Kubono and Yokoi
C18H18Cl4N2O2 and C18H18Cl4N2O2 o537