Amitriptylinium picrate: Conformational disorder

Article abstract of DOI:10.1107/S0108270107037468

In the structure of the title salt [systematic name: 3-(10,11-dihydro-5H- dibenzo[a,d][7]annulen-5-yl-idene)-N,N-dimethyl-propan-1-aminium 2,4,6-trinitro-phenolate] of a tricyclic anti-depressant, C20H24N ⁺·C6H2N3O7 ^-, the dimethyl-amino-propyl subunit possesses a classical static conformational disorder. The central cyclo-hepta-diene ring adopts a bent conformation that is inter-mediate between boat and chair forms, leading to a butterfly shape for the hetero-tricyclic moiety. In a complementary fashion, donors from amitriptyline and acceptors from picrate form inter-molecular C - H...O hydrogen bonds and N - H...O salt bridges. These hydrogen bonds cluster amitriptyline and picrate ions into a closed R 4 ⁴(36) hetero-tetra-mer, whereas inter-molecular C - H...π inter-actions between amitriptyline ions cluster them into homo-dimers. Significant π-π stacking inter-actions are also observed between aromatic rings of amitriptyline and picrate, and these, combined with the C - H...π inter-actions, associate mol-ecules into linear arrays along the [1 1] direction. International Union of Crystallography 2007.

Full text of DOI:10.1107/S0108270107037468

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
in the Cambridge Structural Database (CSD, Version 5.28;
Allen, 2002) revealed that such compounds represent hardly
0.001%
ISSN 0108-2701
Amitriptylinium picrate:
conformational disorder
S. Bindya,a Wing-Tak Wong,b M. A. Ashok,a H. S.
Yathirajana and R. S. Rathorec*
of all reported structures. A great majority of them are
populated by conformational disorders of terminal hydro-
carbon chains and multiple puckering states of alicyclic rings.
The multi-conformational states of a molecule or part thereof,
separated by low-energy barriers, are also represented in
conformational polymorphs. Even if all of the 0.5% of poly-
morph cases present in the CSD (van de Streek & Motherwell,
2005) are included, this under-representation is in sharp
contrast to the otherwise plentiful conformational states of a
molecule that are populated in solution. This anomalous
observation could be partially rationalized by the fact that,
among several conformers in solution, only those that exhibit
similar steric bulk and are relatively disposed in a similar
manner occur in the crystal structure, so that there is a
minimal violation of crystal translational symmetry.
aDepartment of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore
570 006, India, bDepartment of Chemistry, University of Hong Kong, Pokfulam
Road, Pokfulam, Hong Kong SAR, People's Republic of China, and cSchool of
Biotechnology, Devi Ahilya University, Indore 452 017, India, and Oriental
Organization of Molecular and Structural Biology, 203 Agarwal Bhavan,
Malleshwaram, Bangalore 560 055, India
Correspondence e-mail: ravindranath_rathore@yahoo.com
Received 24 May 2007
Accepted 31 July 2007
Online 17 August 2007
In the structure of the title salt [systematic name: 3-(10,11-
dihydro-5H-dibenzo[a,d][7]annulen-5-ylidene)-N,N-dimethyl-
propan-1-aminium 2,4,6-trinitrophenolate] of a tricyclic anti-
depressant, C20H24N+ÁC6H2N3O7 , the dimethylaminopropyl
subunit possesses a classical static conformational disorder.
The central cycloheptadiene ring adopts a bent conformation
that is intermediate between boat and chair forms, leading to a
butter¯y shape for the hetero-tricyclic moiety. In a comple-
mentary fashion, donors from amitriptyline and acceptors
from picrate form intermolecular CÐHÁ Á ÁO hydrogen bonds
and NÐHÁ Á ÁO salt bridges. These hydrogen bonds cluster
amitriptyline and picrate ions into a closed R44(36) hetero-
tetramer, whereas intermolecular CÐHÁ Á Áꢀ interactions
between amitriptyline ions cluster them into homo-dimers.
Signi®cant ꢀ±ꢀ stacking interactions are also observed
between aromatic rings of amitriptyline and picrate, and
these, combined with the CÐHÁ Á Áꢀ interactions, associate
molecules into linear arrays along the [111] direction.
Comment
Amitriptyline (Elavil) is a well known tricyclic antidepressant
with anticholinergic and sedative properties. It is believed to
prevent the reuptake of norepinephrine and serotonin at
neurotransmitters [Garattini et al., 1998; DrugBank (Wishart
et al., 2006) ID APRD00227]. The structure of the title salt,
amitriptylinium picrate, (I), is presented here.
The dimethylaminopropyl subunit (DMAP; atoms N1/C1±
C5) of (I) exhibits a classical static conformational disorder.
There are two conformational states of DMAP, where the
state corresponding to the minor disordered component is
interconvertible from the major component by approximate
rotations of 60, 120 and 120ꢀ about the C4ÐC5, C1ÐC4 and
C1ÐN1 bonds, respectively. The torsion angles in (I) are
provided in Table 1. A text search for conformational disorder
Figure 1
(a) A view of (I), showing the atom-numbering scheme. Only the major
component is shown. Displacement ellipsoids are drawn at the 30%
probability level. (b) The major and minor components of the disordered
DMAP subunit. Dashed lines indicate the minor fraction.
o546 # 2007 International Union of Crystallography
DOI: 10.1107/S0108270107037468
Acta Cryst. (2007). C63, o546±o548

organic compounds
The central seven-membered cycloheptadiene ring of (I)
(C6±C12) adopts a bent conformation (Table 1), giving rise to
an overall butter¯y shape of the tricyclic ring (Fig. 1). The
fused benzene rings (C11±C16 and C7/C8/C17±C20) on either
side subtend an angle of 51.3 (1)ꢀ. The bent transition state is
an intermediate conformation state of a cycloheptane,
between boat and chair, and is characterized in the ideal case
by the following contiguous torsion angles as calculated by
Bocian et al. (1975) and Bocian & Strauss (1977): 75.1, 60.3,
1.8, 1.7, 60.3, 75.1 and 0.0ꢀ. Similar conformations of the
tricyclic ring were also observed in nortriptyline and
amitriptyline hydrochloride (Klein et al., 1991, 1994) and
related compounds (Vijay et al., 2005; Portalone et al., 2007).
The crystal packing of (I) is predominantly stabilized by co-
operative interactions, as shown in Fig. 2. Amitriptyline
(AMP) and picrate (PCT) molecules play a complementary
role. Intermolecular salt bridges and hydrogen bonds are
formed between the donors of AMP and the acceptors of PCT
(Table 2). N1ÐH1(or H10)Á Á ÁO1 salt bridges and C19Ð
H19Á Á ÁO5ii [symmetry code: (ii) 1 x, 1 y, 1 z] hydrogen
bonds cluster them into a hetero-tetramer. This assembly is
characterized by an R44(36) pattern (Bernstein et al., 1995).
Orthogonal to this assemblage, AMP molecules are clustered
into homo-dimers, which are mediated by C14ÐH14Á Á ÁCg1iii
interactions [symmetry code: (iii) x, 1 y, z].
AMP C7/C8/C17±C20 ring) of the same asymmetric unit, with
Ê
a centroid-to-centroid distance of 3.774 (1) A and a perpen-
Ê
dicular distance of 3.475 A. On its other face, PCT is asso-
=
3.406 A, a slippage of 1.348 A and a centroid-to-centroid
ciated by a parallel stacking interaction, with Cg3Á Á ÁCg3iv
Ê
Ê
Ê
distance of 3.663 (1) A [symmetry code: (iv) 1 x, y, 1 z].
These interactions between AMP and PCT pairs, in
combination with CÐHÁ Á Áꢀ interactions with another two
AMP molecules, form a one-dimensional chain along the [111]
direction (Fig. 2). The co-operative association of inter-
molecular interactions into characteristic patterns has been
unambiguously characterized using graph-theory-based nota-
tions (Bernstein et al., 1995). Unfortunately, such notations are
of limited applicability, as they cannot be used to characterize
interactions involving ꢀ-acceptors or those which do not come
under the category of donor±acceptor types, such as aromatic
ꢀ±ꢀ interactions. It would be of particular interest to formu-
late a similar scheme which can be speci®cally applied in those
cases.
Apart from co-operative interactions, the major component
of DMAP is involved in C4ÐH4AÁ Á ÁO3i hydrogen bonding
[symmetry code: (i) x, y, 1 z]. A short contact associated
v
Ê
with the methyl atom, C3ÐH3BÁ Á ÁO4 [HÁ Á ÁA = 2.56 A and
CÐHÁ Á ÁA = 172ꢀ; symmetry code: (v) 1 x, y, 1 z], is also
observed. However, short contacts like this involving methyl
atoms are unlikely to have any structural signi®cance, due to
the very low acidity of the CÐH bond and the rapid rotation
of the methyl group about the N1ÐC3 bond.
Signi®cant ꢀ±ꢀ interactions are also observed in the
packing of (I). Cg3 (the centroid of the PCT C21±C26 ring)
makes a stacking interaction with Cg1 (the centroid of the
Experimental
Compound (I) was prepared by the reaction of AMP with picric acid
at room temperature. Aqueous solutions of amitriptyline hydro-
chloride (0.942 g, 0.03 M) and picric acid (0.689 g, 0.03 M) were mixed
and stirred. The mixture yielded a yellow precipitate, which was
®ltered off, washed thoroughly with water and dried over P2O5 in a
vacuum desiccator. Single crystals of (I) suitable for X-ray diffraction
analysis were grown by slow evaporation of a solution in methanol
(m.p. 393 K).
Crystal data
C20H24N+ÁC6H2N3O7
ꢃ = 85.411 (4)ꢀ
3
Ê
Mr = 506.51
Triclinic, P1
a = 10.0649 (11) A
V = 1256.1 (2) A
Z = 2
Ê
Ê
Mo Kꢁ radiation
1
b = 11.0187 (12) A
ꢄ = 0.10 mm
T = 301 (1) K
Ê
c = 12.0352 (13) A
ꢁ = 73.357 (2)ꢀ
ꢂ = 79.305 (3)ꢀ
0.48 Â 0.31 Â 0.26 mm
Data collection
Bruker SMART CCD area-detector
diffractometer
Absorption correction: multi-scan
(SADABS; Sheldrick, 1996)
Tmin = 0.969, Tmax = 0.975
7632 measured re¯ections
4802 independent re¯ections
3598 re¯ections with I > 2ꢅ(I)
Rint = 0.040
Figure 2
Co-operative interactions observed in (I): intermolecular hydrogen-
bonded R44(36) hetero-tetramers of AMP and PCT along [111], and
association of AMP and PCT into a one-dimensional array along [111],
mediated via CÐHÁ Á Áꢀ and ꢀ±ꢀ stacking interactions. Cg1 and Cg3 are
the centroids of rings C7/C8/C17±C20 and C21±C26, respectively. Only
the major fraction of the disorder is shown. [Symmetry codes: (ii) 1 x,
Re®nement
R[F2 > 2ꢅ(F2)] = 0.058
wR(F2) = 0.178
S = 1.06
4802 re¯ections
365 parameters
15 restraints
H-atom parameters constrained
3
Ê
Áꢆmax = 0.19 e A
3
Ê
0.30 e A
Áꢆmin
=
1
y, 1 z; (iii) x, 1 y, z; (iv) 1 x, y, 1 z.]
C20H24N+ÁC6H2N3O7
o547
ꢁ
Acta Cryst. (2007). C63, o546±o548
Bindya et al.

organic compounds
Table 1
structure: SIR92 (Altomare et al., 1994); program(s) used to re®ne
structure: SHELXL97 (Sheldrick, 1997); molecular graphics:
ORTEP-3 (Farrugia, 1997) and PLATON (Spek, 2003); software
used to prepare material for publication: SHELXL97.
Selected torsion angles (ꢀ).
C2ÐN1ÐC1ÐC4
C3ÐN1ÐC1ÐC4
C20ÐN1ÐC10ÐC4
C30ÐN1ÐC10ÐC4
N1ÐC1ÐC4ÐC5
N1ÐC10ÐC4ÐC5
C1ÐC4ÐC5ÐC6
C10ÐC4ÐC5ÐC6
59.4 (3)
179.4 (3)
178.9 (4)
50.3 (4)
55.6 (3)
64.4 (3)
86.3 (3)
142.7 (3)
C11ÐC12ÐC6ÐC7
C12ÐC6ÐC7ÐC8
C6ÐC7ÐC8ÐC9
C7ÐC8ÐC9ÐC10
C8ÐC9ÐC10ÐC11
C9ÐC10ÐC11ÐC12
C10ÐC11ÐC12ÐC6
66.2 (2)
44.7 (2)
1.6 (3)
18.0 (3)
71.5 (2)
68.4 (2)
5.4 (3)
RSR thanks the Science and Engineering Research
Council, Department of Science and Technology, Government
of India, for a Fast-Track Scientist award, and the Bioinfor-
matics Centre, School of Biotechnology, Devi Ahilya
University, Indore, India, for the use of computational facil-
ities.
Table 2
Hydrogen-bond geometry (A, ).
ꢀ
Ê
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: FA3097). Services for accessing these data are
described at the back of the journal.
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
N1ÐH1Á Á ÁO1
0.87
0.87
0.97
0.93
0.93
1.87
1.88
2.59
2.50
2.87
2.648 (2)
2.648 (3)
3.343 (3)
3.379 (4)
3.667 (3)
149
146
135
158
144
N1ÐH10Á Á ÁO1
C4ÐH4AÁ Á ÁO3i
C19ÐH19Á Á ÁO5ii
C14ÐH14Á Á ÁCg1iii
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restrained to be the same by applying soft SADI restraints
(SHELXL97; Sheldrick, 1997). In the ®nal stage of re®nement, the
statistical fractions of the major and minor disordered components
were held ®xed to the nearest rounded values of 0.6 and 0.4,
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Ê
Ê
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Ê
Ê
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Ê
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v
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Ê
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o548 Bindya et al. C20H24N+ÁC6H2N3O7
Acta Cryst. (2007). C63, o546±o548
ꢁ