Astemizole tetrachlorocuprate(II)

Article abstract of DOI:10.1107/S0108270100007733

The structure of {3-[(4-fluorophenyl)methyl]-1H-benzimidazol- 2-ylidene}{1-[2-(4-methoxyphenyl)ethyl]-4- piperidin-1-io}ammonium tetrachlorocuprate(II), (C₂₈H₃₃FN₄O)[CuCl₄], contains diprotonated cations of aste

Full text of DOI:10.1107/S0108270100007733

metal-organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
1987). The phenylethyl C atoms are disordered over C20±C27
and C200±C270, with site-occupancy factors 0.490 (6) and
0.510 (6), respectively, indicating the presence of two confor-
mers in the crystals. The separation between pairs of C atoms
ISSN 0108-2701
Ê
of the phenylethyl ring is in the range 0.12 A for C25 and
2
1.27 A for C21. The important bond distances are Csp ÐF
Ê
1.366 (5), mean Csp3ÐCsp3 1.515 (10), Csp3ÐCsp2 1.510 (10),
Astemizole tetrachlorocuprate(II)
0
0
Ê
and CÐCaromatic 1.383 (12) A; C22±C27 and C22 ±C27
Ê
aromatic ring distances were constrained at 1.39 (1) A. It is
Ê
interesting to note that C1ÐN3 [1.316 (5) A] is clearly a
Masood Parvez* and Kristin Braitenbach
Department of Chemistry, The University of Calgary, 2500 University Drive NW,
Calgary, Alberta, Canada T2N 1N4
double bond and that in the benzimidazole ring, the mean
distances NÐCsp2 and NÐCaromatic of 1.355 (4) and
Correspondence e-mail: parvez@ucalgary.ca
Ê
1.397 (3) A, respectively, are signi®cantly different from each
3
other. Moreover, the mean Nsp ÐC distance is 1.500 (9) A,
Ê
Received 24 March 2000
Accepted 26 May 2000
while the NÐCsp3 and CÐNsp2 distances are 1.481 (5) and
Ê
1.452 (5) A, respectively.
The structure of {3-[(4-¯uorophenyl)methyl]-1H-benzimi-
dazol-2-ylidene}{1-[2-(4-methoxyphenyl)ethyl]-4-piperidin-1-
io}ammonium tetrachlorocuprate(II), (C28H33FN4O)[CuCl4],
contains diprotonated cations of astemizole hydrogen bonded
2
to three Cl atoms in two different CuCl4 anions, with ClÁ Á ÁN
Ê
distances in the range 3.166 (4)±3.203 (4) A. The geometry
around copper is ¯attened tetrahedral with signi®cantly
different CuÐCl distances which lie in the range
Ê
2.1968 (14)±2.2861 (12) A. The phenylethyl C atoms of the
(4-methoxyphenyl)ethyl group are disordered indicating the
presence of two conformers in the crystals.
Comment
Figure 1
ORTEPII (Johnson, 1976) drawing of (I) with 50% probability ellipsoids;
Astemizole is the active ingredient of `hismanal', a potent
antihistaminic drug which has been classi®ed as a long-lasting
drug with 24 h effectiveness and has very little or no drowsi-
ness effects (Casy, 1991). A lack of sedation effects may be
attributed to the presence of the 1-[2-(4-methoxyphenyl)-
ethyl]-4-piperidinyl moiety in astemizole which may hinder
the penetration of the central nervous system by this drug
(Richards et al., 1984). Continuing our studies on the in¯uence
the disordered C200±C270 atoms are not shown.
The benzimidazole and ¯uorophenyl rings are essentially
planar with maximum deviations of atoms from the least-
Ê
squares planes being 0.033 (3) and 0.005 (3) A, respectively.
The dihedral angle between these planes is 67.77 (11)ꢁ; the
corresponding angle in the two molecules of astemizole is
around 79ꢁ (Peeters et al., 1995). The six-membered piper-
idinyl ring in (I) has a classical chair conformation with
2
of anions of transition metals, e.g. CuCl4 , on the confor-
mation of antihistamines effective on H1 receptors (Parvez &
Sabir, 1997a,b,c, 1998; Parvez, 1998), we have prepared a
diprotonated cationic salt of astemizole. In this paper, we
report the crystal structure of astemizole tetrachloro-
cuprate(II), (I). The crystal structure of astemizole in its free
form has already been reported (Peeters et al., 1995).
puckering parameters (Cremer
&
Pople, 1975)
Q
=
ꢁ
ꢁ
Ê
0.573 (5) A, ꢀ = 1.9 (5) and ' = 67 (17) . The mean plane of
the methoxy group, which is not disordered, is inclined at
11.7 (7) and 21.5 (6)ꢁ to the phenyl rings C22±C27 and C220±
C270, respectively, for the two conformers present in the
crystal. The dihedral angle between the mean planes of these
phenyl rings is 29.2 (3)ꢁ.
2
The CuCl4
geometry with CuÐCl distances between 2.1968 (14) and
anion exhibits a ¯attened tetrahedral
Ê
2.2861 (12) A, the shortest distance being for the Cl atom not
involved in any hydrogen bond. There are two types of ClÐ
CuÐCl angles in the anion, i.e. four angles in the range
97.86 (5)±99.93 (5)ꢁ and the remaining two are 130.27 (5) and
2
Fig. 1 shows an ORTEPII (Johnson, 1976) drawing of (I).
The structure is composed of diprotonated astemizole cations
137.91 (6)ꢁ. Similar geometry for CuCl4 has been reported
in the tetrachlorocuprate salts of clemizole (Parvez & Sabir,
1997a), chloropyramine (Parvez & Sabir, 1997b), triprolidine
(Parvez & Sabir, 1997c), dicytosine (Ogawa et al., 1979) and
fenethazine (Obata et al., 1985).
2
and CuCl4 anions. The molecular dimensions in the aste-
mizole dication are normal and agree well with the corre-
sponding dimensions reported in the literature (Allen et al.,
ꢀ
1216 # 2000 International Union of Crystallography Printed in Great Britain ± all rights reserved
Acta Cryst. (2000). C56, 1216±1217

metal-organic compounds
Table 2
Hydrogen-bonding geometry (A, ).
The astemizole dication is hydrogen bonded to two Cl
atoms of the same anion via its ammonium H atoms [NÁ Á ÁCl
ꢁ
Ê
Ê
3.203 (4) and 3.166 (4) A]. It is also hydrogen bonded to a Cl
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
atom of a symmetry-related anion involving the H atom
Ê
N2ÐH2NÁ Á ÁCl2i
N3ÐH3NÁ Á ÁCl3
N4ÐH4NÁ Á ÁCl4
0.88
0.88
0.93
2.32
2.37
2.24
3.190 (4)
3.203 (4)
3.166 (4)
170
157
171
attached to N2 of its benzimidazole ring [NÁ Á ÁCl 3.190 (4) A].
The details of hydrogen-bonding geometry in (I) have been
provided in Table 2.
Symmetry code: (i) x 1; y; z.
Experimental
The phenylethyl C atoms of the (4-methoxyphenyl)ethyl group are
disordered (see Comment). The N4ÐC20/C200, C20/C200ÐC21/C210
and CÐCaromatic distances in the (4-methoxyphenyl)ethyl group were
The title compound was synthesized by adding CuCl2Á2H2O
(1.0 mmol) to astemizole (2.0 mmol; Sigma Inc.) in HCl (15 ml,
6.0 M) and boiling for 10 min. The solution was allowed to stand at
room temperature whereupon it yielded yellow prismatic crystals
after a few days.
Ê
®xed at 1.48 (1), 1.50 (1) and 1.39 (1) A, respectively, using the
command DFIX and the disordered atoms were re®ned with isotropic
displacement parameters. The H atoms were included in the re®ne-
ment at idealized positions with CÐH = 0.95, 0.98 and 0.99 and NÐH
Ê
= 0.88 and 0.93 A and the isotropic displacement parameters of the H
Crystal data
atoms were tied to the atoms to which they were bonded.
Data collection: SMART (Siemens, 1994); cell re®nement: SAINT
(Siemens, 1995); data reduction: SAINT; program(s) used to solve
structure: SAPI91 (Fan, 1991); program(s) used to re®ne structure:
SHELXTL (Sheldrick, 1997); molecular graphics: TEXSAN (Mole-
cular Structure Corporation, 1994); software used to prepare material
for publication: SHELXTL.
3
(C28H33FN4O)[CuCl4]
Mr = 665.92
Dx = 1.512 Mg m
Mo Kꢂ radiation
Cell parameters from 3724
re¯ections
Monoclinic, P21=n
Ê
a = 9.1099 (7) A
b = 15.9279 (15) A
ꢀ = 1.6±26.4ꢁ
ꢃ = 1.15 mm
T = 193 (2) K
Ê
1
Ê
c = 20.5073 (19) A
ꢁ = 100.445 (2)ꢁ
3
Ê
V = 2926.2 (4) A
Z = 4
Prism, yellow
0.17 Â 0.13 Â 0.05 mm
The authors thank Dr Robert MacDonald, Department of
Chemistry, University of Alberta, Edmonton, for collecting
data on a Bruker P4/RA/SMART 1000 CCD instrument.
Data collection
Bruker P4/RA SMART 1000 CCD
diffractometer
Rint = 0.097
max = 26.4ꢁ
ꢀ
! scans
h = 4 ! 11
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: FR1280). Services for accessing these data are
described at the back of the journal.
Absorption correction: multi-scan
(SADABS: Sheldrick, 1996)
Tmin = 0.83, Tmax = 0.95
14320 measured re¯ections
5981 independent re¯ections
2704 re¯ections with I > 2ꢄ(I)
k = 18 ! 19
l = 25 ! 23
50 standard re¯ections
frequency: beginning and end of
data collection
intensity decay: none
References
Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor,
R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1±19.
Casy, A. F. (1991). Histamine and Histamine Antagonists, edited by B. Uvnas,
pp. 549±572. Berlin: Springer-Verlag.
Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354±1358.
Fan, H.-F. (1991). SAPI91. Rigaku Corporation, Tokyo, Japan.
Johnson, C. K. (1976). ORTEPII. Report ORNL-5138. Oak Ridge National
Laboratory, Tennessee, USA.
Re®nement
Re®nement on F2
R[F2 > 2ꢄ(F2)] = 0.051
wR(F2) = 0.101
S = 0.81
5981 re¯ections
346 parameters
H-atom parameters constrained
w = 1/[ꢄ2(Fo2) + (0.0236P)2]
where P = (Fo2 + 2Fc2)/3
(Á/ꢄ)max < 0.001
3
Ê
Áꢅmax = 0.40 e A
3
Ê
0.37 e A
Áꢅmin
=
Molecular Structure Corporation (1994). TEXSAN. MSC, 3200 Research
Forest Drive, The Woodlands, TX 77381, USA.
Obata, A., Yoshimori, M., Yamada, K. & Kawazura, H. (1985). Bull. Chem.
Soc. Jpn, 58, 437±441.
Table 1
Selected geometric parameters (A, ).
ꢁ
Ê
Ogawa, K., Nishitani, K., Fijiwara, T., Shirotake, S. & Tomita, K. (1979). Acta
Cryst. B35, 965±967.
Parvez, M. (1998). Acta Cryst. C54, 1748±1750.
Parvez, M. & Sabir, A. P. (1997a). Acta Cryst. C53, 675±677.
Parvez, M. & Sabir, A. P. (1997b). Acta Cryst. C53, 678±679.
Parvez, M. & Sabir, A. P. (1997c). Acta Cryst. C53, 679±681.
Parvez, M. & Sabir, A. P. (1998). Acta Cryst. C54, 933±935.
Peeters, O. M., Blaton, N. M. & De Ranter, C. J. (1995). Acta Cryst. C51, 2132±
2135.
Cu1ÐCl1
Cu1ÐCl2
Cu1ÐCl4
Cu1ÐCl3
F1ÐC12
N1ÐC1
2.1968 (14)
2.2382 (13)
2.2545 (13)
2.2861 (12)
1.366 (5)
1.352 (5)
1.400 (5)
1.481 (5)
N2ÐC1
N2ÐC2
N3ÐC1
N3ÐC15
N4ÐC18
N4ÐC17
N4ÐC20
N4ÐC200
1.359 (5)
1.394 (5)
1.316 (5)
1.452 (5)
1.490 (5)
1.496 (6)
1.501 (6)
1.512 (6)
N1ÐC7
N1ÐC8
Richards, D. M., Brogden, R. N., Heel, R. C., Speight, T. M. & Avery, G. S.
(1984). Drugs, 28, 38±61.
Cl1ÐCu1ÐCl2
Cl1ÐCu1ÐCl4
Cl2ÐCu1ÐCl4
Cl1ÐCu1ÐCl3
Cl2ÐCu1ÐCl3
Cl4ÐCu1ÐCl3
C1ÐN1ÐC7
137.91 (6)
99.93 (5)
99.04 (5)
97.86 (5)
97.89 (5)
130.27 (5)
109.7 (3)
125.1 (4)
C7ÐN1ÐC8
C1ÐN2ÐC2
125.1 (3)
109.1 (4)
126.3 (4)
109.7 (4)
103.0 (4)
124.9 (5)
119.9 (5)
101.0 (4)
È
Sheldrick, G. M. (1996). SADABS. University of Gottingen, Germany.
C1ÐN3ÐC15
C18ÐN4ÐC17
C18ÐN4ÐC20
C17ÐN4ÐC20
C18ÐN4ÐC200
C17ÐN4ÐC200
Sheldrick, G. M. (1997). SHELXTL. Version 5.10. Bruker AXS Inc., Madison,
Wisconsin, USA.
Siemens (1994). SMART. Siemens Analytical X-ray Instruments Inc.,
Madison, Wisconsin, USA.
Siemens (1995). SAINT. Version 4.0. Siemens Analytical X-ray Instruments
Inc., Madison, Wisconsin, USA.
C1ÐN1ÐC8
ꢀ
Acta Cryst. (2000). C56, 1216±1217
Parvez and Braitenbach (C28H33FN4O)[CuCl4] 1217