(1S)-1-Phenyl-ethanaminium 4-{[(1S,2S)-1-hy-droxy-2,3-dihydro-1H,1′H- [2,2′-biinden]-2-yl]methyl}benzoate

Article abstract of DOI:10.1107/S0108270112031265

The title mol-ecular salt, C₈H₁₂N⁺· C₂₆H₂₁O₃^-, contains a dimeric indane pharmacophore that demonstrates potent anti-inflammatory activity. The indane group of the anion exhibits some disorder about the α-C atom, which appears common to many structures containing this group. A model to account for the slight disorder was attempted, but this was deemed unsuccessful because applying bond-length con-straints to all the bonds about the α-C atom led to instability in the refinement. The absolute configuration was determined crystallographically as S,S,S by anomalous dispersion methods with reference to both the Flack parameter and Bayesian statistics on Bijvoet differences. The configuration was also determined by an a priori knowledge of the absolute configuration of the (1S)-1-phenyl-ethanaminium counter-ion. The mol-ecules pack in the crystal structure to form an infinite two-dimensional hydrogen-bond network in the (100) plane of the unit cell.

Full text of DOI:10.1107/S0108270112031265

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
2009; Sheridan, Walsh, Jordan et al., 2009). The title
compound, (I), a single enantiomer, is the 1-phenylethan-
aminium salt of 4-{[(1S,2S)-1-hydroxy-2,3-dihydro-1H,10H-
[2,20-biinden]-2-yl]methyl}benzoic acid (PH46) and represents
a first-in-class anti-inflammatory indane scaffold with poten-
tial therapeutic use in the treatment of inflammatory bowel
disease (Frankish & Sheridan, 2012). The crystal structure and
absolute stereochemistry determination of (I) are described
here.
ISSN 0108-2701
(1S)-1-Phenylethanaminium
4-{[(1S,2S)-1-hydroxy-2,3-dihydro-
1H,10H-[2,20-biinden]-2-yl]methyl}-
benzoate
Christopher S. Frampton,a* Tao Zhang,b Gaia A.
Scalabrino,b Neil Frankishc and Helen Sheridanc
aPharmorphix Solid State Services, A Sigma–Aldrich Company, 250 Cambridge
Science Park, Milton Road, Cambridge CB4 0WE, England, bTrino Therapeutics Ltd,
The Tower, Trinity Technology and Enterprise Campus, Pearse Street, Dublin 2,
Ireland, and cDrug Discovery Group, School of Pharmacy and Pharmaceutical
Sciences, Trinity College Dublin, Dublin 2, Ireland
Correspondence e-mail: chris.frampton@sial.com
Received 22 June 2012
Accepted 9 July 2012
Online 19 July 2012
The title molecular salt, C8H12N+ꢀC26H21O3ꢁ, contains a
dimeric indane pharmacophore that demonstrates potent
anti-inflammatory activity. The indane group of the anion
exhibits some disorder about the ꢀ-C atom, which appears
common to many structures containing this group. A model to
account for the slight disorder was attempted, but this was
deemed unsuccessful because applying bond-length con-
straints to all the bonds about the ꢀ-C atom led to instability
in the refinement. The absolute configuration was determined
crystallographically as S,S,S by anomalous dispersion methods
with reference to both the Flack parameter and Bayesian
statistics on Bijvoet differences. The configuration was also
determined by an a priori knowledge of the absolute
configuration of the (1S)-1-phenylethanaminium counter-ion.
The molecules pack in the crystal structure to form an infinite
two-dimensional hydrogen-bond network in the (100) plane of
the unit cell.
The structure of (I) is shown in Fig. 1. The inden-2-yl group,
defined by atoms C18–C26, demonstrates disorder in the
position of the C—C and C C bonds in the five-membered
ring. The disorder manifests itself in the appearance of three
Comment
The indane pharmacophore occurs in many different bioactive
molecules, including the nonsteroidal anti-inflammatory
indane sulindac (Clinoril, Merck) (Scheper et al., 2007; Shiff et
al., 1995) and the protease inhibitor indinavir (Crixivan,
Merck), used as a component of highly active antiretroviral
therapy (HAART) (Vacca et al., 1994; Lin, 1999). As part of
our drug-discovery programme, we have identified a number
of indanes that demonstrate smooth-muscle relaxation and
inhibit mediator release (Sheridan et al., 1990, 1999a,b). More
recently, we have synthesized and characterized a series of
dimeric indanes that demonstrate potent anti-inflammatory
activity (Frankish et al., 2004; Sheridan, Walsh, Cogan et al.,
Figure 1
The molecular structure of (I), showing the atom-labelling scheme.
Displacement ellipsoids are drawn at the 50% probability level for non-H
atoms. The dashed line indicates a hydrogen bond.
Acta Cryst. (2012). C68, o323–o326
doi:10.1107/S0108270112031265
# 2012 International Union of Crystallography o323

organic compounds
˚
refined to values of 1.420 (3) and 1.443 (2) A, respectively
(shown as a square in Fig. 2, indicated with an arrow). A
disorder model incorporating the two different components,
with the sum of the occupancies constrained to unity, was
attempted. However, in order for the refinement to converge
successfully, the displacement parameters for the ꢀ-C atom
C18 and its disordered component C18A had to be
constrained as isotropic. The model converged, yielding
occupancies of the two inden-2-yl components of 0.57 (2) and
0.43 (2). The resulting C C and C—C bond lengths about
˚
C18/C18A were 1.29 (2)/1.52 (2) A for component 1 and
˚
1.35 (2)/1.60 (3) A for component 2 (lower and upper triangles
in Fig. 2, respectively). Further refinement cycles in which
additional bond-length constraints were applied to all bonds
about the ꢀ-C atom led to instability in the refinement. From
this analysis it was concluded that the disorder model was
insufficient and so the data presented here is based on the
ordered model.
For the inden-2-yl moiety, the five-membered C18–C20/
C25/C26 ring is planar, with C18—C19—C20—C25 and C20—
C25—C26—C18 torsion angles of 1.36 (16) and ꢁ0.69 (16)ꢂ,
respectively, whereas the five-membered C9–C11/C16/C17
ring of the indan-2-yl moiety adopts an envelope conforma-
Figure 2
A scatterplot of C C versus C—C bond lengths for inden-2-yl fragments
in the CSD. See the Comment for an explanation of the symbols.
potential H-atom positions in a difference Fourier synthesis
about each of atoms C19 and C26, both ꢀ to atom C18. The
potential disorder in this group was also revealed through a
Hirshfeld rigid-bond test (Hirshfeld, 1976), where the differ-
ences in the components of the anisotropic displacement
parameters along the C18—C19 and C18—C26 bonds exceed
6 s.u.
A simple Conquest (Macrae et al., 2008) search of the
Cambridge Structural Database (CSD, Version 5.33; Allen,
2002) for inden-2-yl fragments as shown in (II) (see Scheme),
where R1 is defined as any substituent other than hydrogen,
returned a total of 33 entries. The disorder present in the
inden-2-yl fragment was documented in a number of struc-
tures and the use of a two-part disorder model to separate the
two components was attempted [see, for example, CSD
refcodes APOVUX (Nikitin et al., 2010), CORBOB (Nikitin et
al., 2009), OGEKAN (Nikulin et al., 2008) and TENBAP (Li et
al., 1996)], although in the case of APOVUX it was specifically
noted that the disorder model failed. A scatterplot of C—C
distances versus C C distances is shown in Fig. 2. The
correlation between these two parameters is clear, such that
for structures where there is no disorder present, or where the
disorder model has been successfully implemented, the values
of the C C and C—C bond lengths are clearly different, ca
˚
tion or E form, with atom C9 displaced by 0.478 (2) A from
the mean plane defined by the other four atoms.
The absolute configuration of (I), viz. S, S and S at the chiral
centres C9, C10 and C33, respectively, was determined by
reference to the a priori knowledge of the chirality of the (S)-
(ꢁ)-methylbenzylamine used in the salt-formation step and by
anomalous dispersion methods (Flack, 1983). The determi-
nation of the absolute configuration of (I) by anomalous
dispersion methods was likely to be challenging, given that the
molecular formula and asymmetric unit contain only a single
N and three O atoms. To maximize the likelihood of success, a
full sphere of data was collected using Cu Kꢀ radiation to a
˚
maximum resolution of 0.80 A. A total of 25 532 reflections
were collected, yielding a Flack parameter x and standard
uncertainty u for this structure of 0.00 (15) based on 2343
Friedel pairs. The value of u is slightly beyond the limit of
enantiopure-sufficient distinguishing power (Flack & Bernar-
dinelli, 1999, 2000), and for further confirmation of the abso-
lute configuration a determination using Bayesian statistics on
Bijvoet differences (Hooft et al., 2008), as implemented in the
program PLATON (Spek, 2009), was performed. This gave
probability values p3(ok), p3(twin) and p3(wrong) of 1.000,
0.000 and 0.000, respectively. The calculation was based on
2343 Bijvoet pairs. The absolute structure parameter and
standard uncertainty calculated using this method was
0.11 (4). An improvement in the absolute structure parameter
can be made using a Student t distribution rather than a
Gaussian distribution (Hooft et al., 2010), giving ꢁ0.03 (13)
for a ꢁ parameter of 9.79. The overall p3 probability values
calculated using this method remain unchanged at 1.000, 0.000
and 0.000.
˚
1.35 and 1.50 A, respectively (e.g. OGEKAN), whereas for
structures that demonstrate the disorder phenomenon these
two bond lengths appear to be correlated and ultimately
˚
equilibrate to a value of ca 1.42 A. The outlier point circled in
Fig. 2 (QUGWUK; Basavaiah et al., 2001) is due to the
incorrect assignment of the C-atom type when geometrically
˚
placing the H atoms; the 1.378 and 1.463 A bond lengths
should be assigned as C C and C—C bonds, respectively, and
not vice versa. The complete list of structures contained within
this data set is available in the Supplementary materials.
In keeping with the findings above, the C C and C—C
bond lengths (C18 C19 and C18—C26, respectively) in (I)
The packing arrangement for (I) is best descibed as an
infinite two-dimensional hydrogen-bond network in the (100)
plane of the unit cell. The primary building block of this
o324 Frampton et al. C8H12N+ꢀC26H21O3
Acta Cryst. (2012). C68, o323–o326
ꢁ
ꢃ

organic compounds
Figure 3
Aview of part of the crystal packing of (I). The figure shows the four hydrogen-bond interactions (thin lines) and the formation of the R33(8) ring. [In the
electronic version of the paper, molecules generated by the symmetry codes (i), (ii) and (iii) are represented by the colours green, red and blue,
respectively, with hydrogen bonds shown as thin turquoise lines and incomplete hydrogen bonds as thin red lines.] For clarity, only H atoms attached to
heteroatoms are shown. (The symmetry codes are as given in Table 1.)
network is the formation of an infinite chain of PH46 anions
through a translational symmetry operation along the c axis of
the unit cell. This interaction is formed by a single hydrogen
bond from the hydroxy group of the substituted indenyl group,
acting as donor, to a carbonyl O atom of the benzoate group,
interaction with the carbonyl O atom of a PH46 anion to form
a larger overall two-dimensional network in the (100) plane;
N1—H1Dꢀ ꢀ ꢀO2iii = 2.7991 (17) A. Fig. 3 shows the four
˚
hydrogen-bond interactions described above. An overall view
of the crystal packing down the a axis of the unit cell is shown
in Fig. 4. All potential hydrogen-bond donors are utilized in
the hydrogen-bonding arrangement, thus concurring with
Etter’s first rule of hydrogen bonding for organic compounds,
which states that all good H-atom donors and acceptors are
used in hydrogen bonding (Etter, 1990).
i
˚
acting as acceptor [O3—H3Aꢀ ꢀ ꢀO2 = 2.7113 (14) A; see
Table 1 for hydrogen-bond geometry and symmetry codes].
The hydrogen-bond network is extended by the formation of
three further interactions linking the PH46 anion to the (1S)-
1-phenylethanaminium cation. These three interactions are
formed by the –NH3+ ammonium group acting as donor to O
atoms of three different PH46 anions acting as acceptors. Two
of these interactions bridge the infinite chain along the c axis
Experimental
to form an R33(8) ring (Bernstein et al., 1995); N1—H1ꢀ ꢀ ꢀO1 =
To an ethanol (7.5 ml) suspension of 4-{[(1S,2S)-1-hydroxy-2,3-
dihydro-1H,10H-[2,20-biinden]-2-yl]methyl}benzoic acid (PH46; 0.5 g,
1.31 mmol) was added (S)-(ꢁ)-ꢀ-methylbenzylamine (0.2 ml,
1.5 mmol, 1.1 equivalents) portionwise. This reaction mixture was
stirred for 2 h at 323 K and then left overnight at room temperature.
Since no solid material was obtained, the solution was then concen-
trated under reduced pressure and diethyl ether (2 ml) was added to
the flask. A white solid was immediately observed, which was further
washed with diethyl ether (3 ꢄ 4 ml). The organic solvent was
removed using a Pasteur pipette and the remaining white solid was
dried in a vacuum oven at 313 K (yield 0.56 g, 85%). Crystals of the
salt, (I), were obtained by dissolving the crude material (ca 100 mg) in
MeOH (3 ml) in a flat-bottomed sample tube, followed by the addi-
tion of diethyl ether (6 ml), which was added until the sample solution
became slightly cloudy. The solution was filtered and placed in a dry-
box at room temperature. A small amount of tetrahydrofuran (ca
0.5 ml) was added to the diethyl ether–methanol solution. After 5 d,
colourless crystals of (I) were obtained (m.p. 467.2–467.9 K). 1H NMR
(100 MHz, d6-DMSO): ꢂ 1.33 (d, 3H, J = 6.7 Hz), 2.68 (d, 1H,
J = 13.5 Hz), 2.94, (d, 1H, J = 15.5 Hz), 2.99 (d, 1H, J = 15.5 Hz), 3.17
(d, 1H, J = 13.6 Hz), 3.44 (d, 1H, J= 23.0 Hz), 3.58 (d, 1H, J = 23.0 Hz),
4.12 (q, 1H, J = 6.7 Hz), 5.05 (s, 1H), 5.85 (br s, 1H), 6.41 (s, 1H), 6.86
(d, 2H, J = 8.2 Hz), 7.08 (td, 1H, J = 7.3, 1.3 Hz), 7.14–7.44 (m,
aromatic 12H), 7.65 (d, 2H, J = 8.2 Hz).
ii
˚
˚
2.6697 (16) A and N1—H1Cꢀ ꢀ ꢀO3 = 2.8799 (18) A. The
–NH3+ ammonium group of the cation makes a further donor
Figure 4
The packing of (I), viewed down the a axis, with hydrogen bonds shown as
thin lines. (In the electronic version of the paper, hydrogen bonds are
shown as thin turquoise lines and incomplete hydrogen bonds as thin red
lines.) For clarity, only H atoms attached to heteroatoms are shown.
C8H12N+ꢀC26H21O3
o325
ꢁ
ꢃ
Acta Cryst. (2012). C68, o323–o326
Frampton et al.

organic compounds
Table 1
Hydrogen-bond geometry (A, ).
The authors are grateful to Andrew Carr of Phamorphix for
1
his assistance with the H NMR assignment and to Professor
ꢂ
˚
A. L. Spek for helpful comments regarding the probability
analysis.
D—Hꢀ ꢀ ꢀA
D—H
Hꢀ ꢀ ꢀA
Dꢀ ꢀ ꢀA
D—Hꢀ ꢀ ꢀA
O3—H3Aꢀ ꢀ ꢀO2i
N1—H1Bꢀ ꢀ ꢀO3ii
N1—H1Cꢀ ꢀ ꢀO2iii
N1—H1Dꢀ ꢀ ꢀO1
0.85 (2)
0.91 (2)
0.92 (2)
0.91 (2)
1.86 (2)
2.05 (2)
1.88 (2)
1.77 (2)
2.7113 (14)
2.8799 (18)
2.7991 (17)
2.6697 (16)
177 (2)
151 (2)
178 (2)
174 (2)
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: SK3440). Services for accessing these data are
described at the back of the journal.
1
2
Symmetry codes: (i) x; y; z ꢁ 1; (ii) x; y; z þ 1; (iii) ꢁx þ 2; y þ ; ꢁz þ 2.
References
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Crystal data
C8H12N+ꢀC26H21O3
ꢁ
3
˚
V = 1327.68 (6) A
Z = 2
Cu Kꢀ radiation
ꢄ = 0.63 mmꢁ1
T = 100 K
Mr = 503.61
Monoclinic, P21
a = 11.0350 (3) A
˚
˚
b = 10.1713 (3) A
˚
c = 11.8533 (3) A
0.50 ꢄ 0.47 ꢄ 0.42 mm
ꢃ = 93.678 (2)ꢂ
Data collection
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Agilent SuperNova Dual
diffractometer, with Cu at zero
and an Atlas detector
Absorption correction: multi-scan
(CrysAlis PRO; Agilent, 2011)
Tmin = 0.749, Tmax = 1.000
25532 measured reflections
5221 independent reflections
5157 reflections with I > 2ꢅ(I)
Rint = 0.026
Refinement
R[F2 > 2ꢅ(F2)] = 0.035
wR(F2) = 0.098
S = 1.01
5221 reflections
362 parameters
1 restraint
H atoms treated by a mixture of
independent and constrained
refinement
ꢁ3
˚
Áꢆmax = 0.21 e A
ꢁ3
˚
Áꢆmin = ꢁ0.21 e A
Absolute structure: Flack (1983),
with 2343 Friedel pairs
Flack parameter: 0.00 (15)
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H atoms bonded to heteroatoms were located in a difference map
and refined. Other H atoms were positioned geometrically and
refined using a riding model (including free rotation about the methyl
˚
C—C bond), with C—H = 0.95–0.99 A and Uiso(H) = 1.5Ueq(C) for
methyl groups or 1.2Ueq(C) otherwise.
Data collection: CrysAlis PRO (Agilent, 2011); cell refinement:
CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to
solve structure: SHELXTL (Sheldrick, 2008); program(s) used to
refine structure: SHELXTL; molecular graphics: SHELXTL and
Mercury (Macrae et al., 2008); software used to prepare material for
publication: SHELXTL and Mercury.
o326 Frampton et al. C8H12N+ꢀC26H21O3
Acta Cryst. (2012). C68, o323–o326
ꢁ
ꢃ

supplementary materials
supplementary materials
Acta Cryst. (2012). C68, o323–o326 [doi:10.1107/S0108270112031265]
(1S)-1-Phenylethanaminium 4-{[(1S,2S)-1-hydroxy-2,3-dihydro-1H,1′H-[2,2′-
biinden]-2-yl]methyl}benzoate
Christopher S. Frampton, Tao Zhang, Gaia A. Scalabrino, Neil Frankish and Helen Sheridan
(1S)-1-Phenylethanaminium 4-{[(1S,2S)-1-hydroxy-2,3-dihydro-1H,1′H- [2,2′-biinden]-2-yl]methyl}benzoate
Crystal data
C8H12N+·C26H21O3−
Mr = 503.61
Dx = 1.260 Mg m−3
Melting point: 467.5 K
Cu Kα radiation, λ = 1.54178 Å
Cell parameters from 17123 reflections
θ = 3.7–75.9°
Monoclinic, P21
a = 11.0350 (3) Å
b = 10.1713 (3) Å
c = 11.8533 (3) Å
β = 93.678 (2)°
V = 1327.68 (6) Å3
Z = 2
µ = 0.63 mm−1
T = 100 K
Block, yellow
0.50 × 0.47 × 0.42 mm
F(000) = 536
Data collection
Agilent SuperNova Dual
diffractometer, with Cu at zero and an Atlas
detector
Radiation source: SuperNova (Cu) X-ray
Source
Tmin = 0.749, Tmax = 1.000
25532 measured reflections
5221 independent reflections
5157 reflections with I > 2σ(I)
Rint = 0.026
Mirror monochromator
θmax = 74.5°, θmin = 3.7°
Detector resolution: 10.5598 pixels mm-1
ω scans
h = −13→13
k = −11→12
l = −14→14
Absorption correction: multi-scan
(CrysAlis PRO; Agilent, 2011)
Refinement
Refinement on F2
Least-squares matrix: full
R[F2 > 2σ(F2)] = 0.035
wR(F2) = 0.098
H atoms treated by a mixture of independent
and constrained refinement
w = 1/[σ2(Fo2) + (0.075P)2 + 0.250P]
where P = (Fo2 + 2Fc2)/3
S = 1.01
5221 reflections
362 parameters
(Δ/σ)max < 0.001
Δρmax = 0.21 e Å−3
Δρmin = −0.21 e Å−3
1 restraint
Extinction correction: SHELXTL (Sheldrick,
2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Extinction coefficient: 0.0021 (4)
Absolute structure: Flack (1983), with 2343
Friedel pairs
Primary atom site location: structure-invariant
direct methods
Secondary atom site location: difference Fourier
map
Hydrogen site location: inferred from
neighbouring sites
Flack parameter: 0.00 (15)
Acta Cryst. (2012). C68, o323–o326
sup-1

supplementary materials
Special details
Experimental. CrysAlisPro, Agilent Technologies, Version 1.171.35.19 (release 27-10-2011 CrysAlis171 .NET)
(compiled Oct 27 2011,15:02:11) Empirical absorption correction using spherical harmonics, implemented in SCALE3
ABSPACK scaling algorithm.
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)
x
y
z
Uiso*/Ueq
O1
0.97227 (10)
0.92573 (9)
0.89439 (9)
0.9027 (19)
0.91707 (13)
0.9223
0.67327 (12)
0.46529 (11)
0.51048 (11)
0.499 (2)
0.83449 (8)
0.87703 (8)
0.09869 (8)
0.029 (2)
0.0226 (2)
0.0191 (2)
0.0182 (2)
0.033 (6)*
0.0194 (3)
0.023*
O2
O3
H3A
C1
0.37857 (15)
0.2909
0.52630 (12)
0.4994
H1A
C2
0.92760 (13)
0.9402
0.40249 (15)
0.3312
0.64190 (12)
0.6931
0.0192 (3)
0.023*
H2A
C3
0.91987 (11)
0.94029 (12)
0.89799 (13)
0.8904
0.52948 (15)
0.55850 (15)
0.63239 (15)
0.7196
0.68328 (11)
0.80808 (11)
0.60755 (11)
0.6349
0.0156 (3)
0.0158 (3)
0.0185 (3)
0.022*
C4
C5
H5A
C6
0.88715 (13)
0.8714
0.60794 (15)
0.6790
0.49189 (12)
0.4411
0.0193 (3)
0.023*
H6A
C7
0.89896 (11)
0.90019 (12)
0.9452
0.48130 (15)
0.45817 (16)
0.3758
0.44897 (11)
0.32278 (10)
0.3104
0.0161 (3)
0.0174 (3)
0.021*
C8
H8A
H8B
C9
0.9459
0.5308
0.2895
0.021*
0.77439 (12)
0.79016 (12)
0.7962
0.44829 (15)
0.43611 (15)
0.3421
0.25795 (11)
0.12766 (11)
0.1039
0.0161 (3)
0.0168 (3)
0.020*
C10
H10A
C11
C12
H12A
C13
H13A
C14
H14A
C15
H15A
C16
C17
H17A
H17B
C18
C19
H19A
C20
C21
H21A
C22
0.67726 (12)
0.63315 (13)
0.6692
0.50009 (15)
0.49669 (17)
0.4411
0.07553 (11)
−0.03744 (12)
−0.0904
0.0181 (3)
0.0219 (3)
0.026*
0.53492 (14)
0.5038
0.57693 (18)
0.5765
−0.07056 (13)
−0.1472
0.0257 (3)
0.031*
0.48202 (13)
0.4147
0.65749 (18)
0.7111
0.00710 (15)
−0.0169
0.0275 (3)
0.033*
0.52649 (13)
0.4900
0.66076 (17)
0.7157
0.12012 (14)
0.1732
0.0238 (3)
0.029*
0.62537 (12)
0.69704 (13)
0.6422
0.58175 (15)
0.57468 (15)
0.5681
0.15320 (12)
0.26644 (12)
0.3291
0.0185 (3)
0.0185 (3)
0.022*
0.7495
0.6530
0.2786
0.022*
0.70480 (12)
0.75503 (14)
0.8364
0.32897 (15)
0.20146 (16)
0.1762
0.29625 (11)
0.31348 (12)
0.3031
0.0166 (3)
0.0226 (3)
0.027*
0.65735 (13)
0.65690 (16)
0.7294
0.11507 (16)
−0.01722 (18)
−0.0677
0.35061 (11)
0.37918 (13)
0.3798
0.0205 (3)
0.0278 (3)
0.033*
0.54745 (18)
−0.07482 (19)
0.40716 (14)
0.0320 (4)
Acta Cryst. (2012). C68, o323–o326
sup-2

supplementary materials
H22A
C23
0.5454
−0.1657
0.4256
0.038*
0.44189 (16)
0.3683
−0.0006 (2)
−0.0413
0.40821 (14)
0.4270
0.0318 (4)
0.038*
H23A
C24
0.44272 (14)
0.3709
0.13288 (18)
0.1840
0.38206 (13)
0.3843
0.0269 (3)
0.032*
H24A
C25
0.55085 (14)
0.57753 (14)
0.5273
0.18992 (16)
0.32620 (17)
0.3500
0.35255 (11)
0.31758 (13)
0.2484
0.0210 (3)
0.0239 (3)
0.029*
C26
H26A
H26B
N1
0.5602
0.3890
0.3783
0.029*
0.90975 (11)
0.9082 (19)
0.966 (2)
0.933 (2)
0.81467 (13)
0.8446
0.78051 (13)
0.710 (2)
0.840 (2)
0.749 (2)
1.06674 (17)
1.0993
1.02795 (10)
1.0743 (19)
1.0589 (18)
0.961 (2)
0.92266 (13)
0.9942
0.0189 (3)
0.025 (5)*
0.028 (5)*
0.031 (5)*
0.0221 (3)
0.026*
H1B
H1C
H1D
C27
H27A
C28
0.80522 (14)
0.8271
1.15072 (17)
1.2406
0.82987 (14)
0.8386
0.0253 (3)
0.030*
H28A
C29
0.76376 (14)
0.7576
1.10320 (18)
1.1604
0.72436 (14)
0.6609
0.0273 (3)
0.033*
H29A
C30
0.73157 (15)
0.7041
0.9727 (2)
0.9399
0.71210 (13)
0.6399
0.0303 (4)
0.036*
H30A
C31
0.73922 (14)
0.7161
0.88904 (18)
0.7995
0.80497 (13)
0.7961
0.0253 (3)
0.030*
H31A
C32
0.78069 (12)
0.78543 (13)
0.7257
0.93597 (16)
0.84192 (16)
0.7699
0.91144 (12)
1.01074 (12)
0.9927
0.0198 (3)
0.0200 (3)
0.024*
C33
H33A
C34
0.75416 (15)
0.6714
0.90403 (17)
0.9394
1.12179 (13)
1.1140
0.0256 (3)
0.038*
H34A
H34B
H34C
0.8114
0.9754
1.1413
0.038*
0.7595
0.8374
1.1816
0.038*
Atomic displacement parameters (Å2)
U11
U22
U33
U12
U13
U23
O1
O2
O3
C1
0.0316 (5)
0.0244 (5)
0.0196 (5)
0.0247 (7)
0.0256 (7)
0.0147 (6)
0.0155 (6)
0.0224 (6)
0.0244 (7)
0.0140 (5)
0.0169 (6)
0.0182 (6)
0.0195 (6)
0.0188 (6)
0.0224 (7)
0.0229 (7)
0.0215 (6)
0.0211 (6)
0.0244 (6)
0.0182 (7)
0.0192 (8)
0.0202 (7)
0.0199 (7)
0.0174 (7)
0.0183 (7)
0.0218 (8)
0.0230 (8)
0.0191 (7)
0.0201 (7)
0.0191 (7)
0.0258 (8)
0.0319 (9)
0.0148 (4)
−0.0046 (4)
0.0015 (4)
0.0014 (4)
0.0020 (3)
0.0024 (3)
0.0016 (5)
0.0021 (5)
0.0010 (4)
0.0015 (4)
−0.0010 (5)
−0.0036 (5)
0.0006 (4)
0.0004 (5)
0.0011 (5)
0.0008 (5)
0.0002 (5)
−0.0021 (5)
−0.0074 (5)
−0.0027 (4)
0.0013 (4)
−0.0004 (4)
−0.0028 (5)
0.0036 (5)
−0.0004 (5)
−0.0004 (5)
−0.0007 (5)
0.0037 (5)
0.0000 (5)
0.0010 (5)
−0.0005 (5)
−0.0004 (5)
0.0022 (5)
0.0016 (6)
0.0068 (6)
0.0119 (4)
0.0107 (4)
0.0154 (7)
0.0130 (6)
0.0119 (6)
0.0121 (6)
0.0153 (6)
0.0147 (6)
0.0123 (6)
0.0122 (6)
0.0110 (5)
0.0109 (6)
0.0163 (6)
0.0170 (6)
0.0212 (7)
−0.0016 (4)
0.0024 (6)
C2
0.0025 (6)
C3
−0.0012 (5)
0.0017 (5)
C4
C5
−0.0019 (5)
−0.0030 (5)
−0.0024 (5)
−0.0015 (5)
−0.0007 (5)
−0.0022 (5)
−0.0042 (5)
−0.0065 (6)
−0.0076 (6)
C6
C7
C8
C9
C10
C11
C12
C13
Acta Cryst. (2012). C68, o323–o326
sup-3

supplementary materials
C14
C15
C16
C17
C18
C19
C20
C21
C22
C23
C24
C25
C26
N1
0.0184 (7)
0.0190 (6)
0.0186 (6)
0.0214 (6)
0.0184 (6)
0.0232 (7)
0.0257 (7)
0.0378 (9)
0.0513 (10)
0.0354 (9)
0.0241 (7)
0.0240 (7)
0.0275 (8)
0.0235 (6)
0.0195 (6)
0.0230 (7)
0.0241 (7)
0.0306 (8)
0.0274 (7)
0.0159 (6)
0.0188 (6)
0.0280 (7)
0.0290 (9)
0.0235 (8)
0.0198 (8)
0.0198 (7)
0.0217 (7)
0.0265 (9)
0.0243 (8)
0.0250 (9)
0.0242 (9)
0.0367 (10)
0.0343 (9)
0.0264 (8)
0.0260 (8)
0.0185 (7)
0.0261 (8)
0.0236 (9)
0.0313 (9)
0.0383 (10)
0.0253 (8)
0.0231 (8)
0.0211 (8)
0.0276 (9)
0.0341 (8)
0.0287 (7)
0.0171 (6)
0.0145 (6)
0.0093 (5)
0.0180 (6)
0.0115 (6)
0.0212 (7)
0.0213 (7)
0.0237 (7)
0.0224 (7)
0.0126 (6)
0.0188 (6)
0.0145 (6)
0.0207 (7)
0.0297 (8)
0.0262 (7)
0.0212 (7)
0.0226 (8)
0.0204 (7)
0.0200 (7)
0.0220 (7)
−0.0009 (6)
−0.0008 (6)
−0.0030 (5)
0.0008 (5)
−0.0055 (6)
0.0004 (6)
0.0008 (5)
0.0019 (5)
−0.0013 (5)
0.0004 (5)
0.0010 (5)
0.0062 (6)
0.0085 (7)
0.0042 (6)
0.0029 (5)
0.0016 (5)
0.0068 (5)
0.0002 (4)
0.0022 (5)
0.0043 (6)
−0.0007 (6)
−0.0051 (6)
−0.0038 (6)
0.0006 (5)
0.0009 (5)
0.0072 (6)
0.0099 (7)
0.0034 (6)
0.0020 (5)
0.0000 (5)
−0.0009 (5)
0.0026 (6)
−0.0007 (5)
0.0033 (6)
0.0025 (6)
0.0030 (7)
0.0057 (7)
−0.0006 (6)
0.0001 (6)
−0.0015 (5)
0.0000 (6)
0.0042 (6)
0.0087 (7)
0.0020 (7)
0.0000 (6)
0.0013 (6)
0.0005 (6)
0.0024 (6)
−0.0004 (5)
−0.0027 (6)
−0.0025 (6)
0.0013 (7)
−0.0089 (7)
−0.0149 (7)
−0.0045 (6)
−0.0035 (6)
−0.0008 (6)
−0.0017 (5)
−0.0024 (6)
−0.0021 (6)
−0.0014 (6)
−0.0053 (7)
−0.0048 (6)
−0.0026 (5)
−0.0029 (5)
0.0029 (6)
C27
C28
C29
C30
C31
C32
C33
C34
Geometric parameters (Å, º)
O1—C4
1.2534 (19)
C18—C26
1.443 (2)
O2—C4
1.2686 (18)
1.4365 (17)
0.85 (2)
C19—C20
C19—H19A
C20—C21
C20—C25
C21—C22
C21—H21A
C22—C23
C22—H22A
C23—C24
C23—H23A
C24—C25
C24—H24A
C25—C26
C26—H26A
C26—H26B
N1—C33
1.479 (2)
0.9500
O3—C10
O3—H3A
C1—C2
1.388 (2)
1.402 (2)
1.401 (2)
0.9500
1.389 (2)
1.396 (2)
0.9500
C1—C7
C1—H1A
C2—C3
1.386 (2)
0.9500
1.389 (3)
0.9500
C2—H2A
C3—C5
1.390 (2)
1.5111 (17)
1.3910 (19)
0.9500
1.393 (3)
0.9500
C3—C4
C5—C6
1.391 (2)
0.9500
C5—H5A
C6—C7
1.394 (2)
0.9500
1.482 (2)
0.9900
C6—H6A
C7—C8
1.5152 (17)
1.5463 (17)
0.9900
0.9900
C8—C9
1.5092 (19)
0.91 (2)
0.92 (2)
0.91 (2)
1.386 (2)
1.391 (2)
0.9500
C8—H8A
C8—H8B
C9—C18
C9—C17
C9—C10
C10—C11
C10—H10A
C11—C16
N1—H1B
0.9900
N1—H1C
1.521 (2)
1.550 (2)
1.5701 (17)
1.5029 (19)
1.0000
N1—H1D
C27—C32
C27—C28
C27—H27A
C28—C29
C28—H28A
1.391 (2)
0.9500
1.390 (2)
Acta Cryst. (2012). C68, o323–o326
sup-4

supplementary materials
C11—C12
C12—C13
C12—H12A
C13—C14
C13—H13A
C14—C15
C14—H14A
C15—C16
C15—H15A
C16—C17
C17—H17A
C17—H17B
C18—C19
1.3956 (19)
1.393 (2)
0.9500
C29—C30
C29—H29A
C30—C31
1.379 (3)
0.9500
1.390 (2)
0.9500
1.389 (3)
0.9500
C30—H30A
C31—C32
1.399 (2)
0.9500
1.397 (2)
0.9500
C31—H31A
C32—C33
1.515 (2)
1.520 (2)
1.0000
1.391 (2)
0.9500
C33—C34
C33—H33A
C34—H34A
C34—H34B
C34—H34C
1.5153 (19)
0.9900
0.9800
0.9800
0.9900
0.9800
1.420 (2)
C10—O3—H3A
C2—C1—C7
C2—C1—H1A
C7—C1—H1A
C3—C2—C1
C3—C2—H2A
C1—C2—H2A
C2—C3—C5
C2—C3—C4
C5—C3—C4
O1—C4—O2
O1—C4—C3
O2—C4—C3
C3—C5—C6
C3—C5—H5A
C6—C5—H5A
C5—C6—C7
C5—C6—H6A
C7—C6—H6A
C6—C7—C1
C6—C7—C8
C1—C7—C8
C7—C8—C9
C7—C8—H8A
C9—C8—H8A
C7—C8—H8B
C9—C8—H8B
H8A—C8—H8B
C18—C9—C8
C18—C9—C17
C8—C9—C17
C18—C9—C10
C8—C9—C10
C17—C9—C10
O3—C10—C11
107.5 (15)
121.07 (14)
119.5
C19—C18—C9
124.88 (13)
125.69 (13)
107.47 (13)
126.3
C26—C18—C9
C18—C19—C20
C18—C19—H19A
C20—C19—H19A
C21—C20—C25
C21—C20—C19
C25—C20—C19
C20—C21—C22
C20—C21—H21A
C22—C21—H21A
C23—C22—C21
C23—C22—H22A
C21—C22—H22A
C22—C23—C24
C22—C23—H23A
C24—C23—H23A
C25—C24—C23
C25—C24—H24A
C23—C24—H24A
C24—C25—C20
C24—C25—C26
C20—C25—C26
C18—C26—C25
C18—C26—H26A
C25—C26—H26A
C18—C26—H26B
C25—C26—H26B
119.5
120.60 (13)
119.7
126.3
120.44 (15)
131.50 (15)
108.06 (14)
118.68 (16)
120.7
119.7
119.03 (12)
121.31 (13)
119.60 (13)
125.47 (12)
116.64 (12)
117.87 (13)
120.15 (14)
119.9
120.7
120.73 (17)
119.6
119.6
120.69 (16)
119.7
119.9
121.38 (14)
119.3
119.7
118.71 (16)
120.6
119.3
117.70 (12)
120.71 (13)
121.47 (13)
115.85 (11)
108.3
120.6
120.73 (16)
130.50 (15)
108.76 (13)
106.28 (14)
110.5
108.3
108.3
110.5
108.3
110.5
107.4
110.5
110.97 (11)
110.60 (11)
113.23 (12)
108.70 (11)
109.95 (10)
103.03 (11)
109.20 (12)
H26A—C26—H26B
C33—N1—H1B
C33—N1—H1C
H1B—N1—H1C
C33—N1—H1D
H1B—N1—H1D
H1C—N1—H1D
108.7
111.0 (13)
111.2 (14)
108.5 (18)
109.9 (14)
105 (2)
110.8 (19)
Acta Cryst. (2012). C68, o323–o326
sup-5

supplementary materials
O3—C10—C9
109.55 (11)
103.24 (11)
111.5
C32—C27—C28
C32—C27—H27A
C28—C27—H27A
C29—C28—C27
C29—C28—H28A
C27—C28—H28A
C30—C29—C28
C30—C29—H29A
C28—C29—H29A
C29—C30—C31
C29—C30—H30A
C31—C30—H30A
C30—C31—C32
C30—C31—H31A
C32—C31—H31A
C27—C32—C31
C27—C32—C33
C31—C32—C33
N1—C33—C32
120.48 (15)
119.8
C11—C10—C9
O3—C10—H10A
C11—C10—H10A
C9—C10—H10A
C16—C11—C12
C16—C11—C10
C12—C11—C10
C13—C12—C11
C13—C12—H12A
C11—C12—H12A
C14—C13—C12
C14—C13—H13A
C12—C13—H13A
C13—C14—C15
C13—C14—H14A
C15—C14—H14A
C16—C15—C14
C16—C15—H15A
C14—C15—H15A
C11—C16—C15
C11—C16—C17
C15—C16—C17
C16—C17—C9
119.8
111.5
120.09 (16)
120.0
111.5
121.13 (14)
110.62 (12)
127.79 (14)
118.24 (15)
120.9
120.0
119.79 (15)
120.1
120.1
120.25 (15)
119.9
120.9
120.76 (14)
119.6
119.9
120.36 (16)
119.8
119.6
120.86 (15)
119.6
119.8
119.01 (15)
122.40 (13)
118.59 (14)
110.62 (11)
108.06 (12)
114.33 (13)
107.9
119.6
118.51 (15)
120.7
120.7
N1—C33—C34
120.49 (13)
110.15 (12)
129.23 (14)
103.90 (12)
111.0
C32—C33—C34
N1—C33—H33A
C32—C33—H33A
C34—C33—H33A
C33—C34—H34A
C33—C34—H34B
107.9
107.9
C16—C17—H17A
C9—C17—H17A
C16—C17—H17B
C9—C17—H17B
H17A—C17—H17B
C19—C18—C26
109.5
111.0
109.5
111.0
H34A—C34—H34B
C33—C34—H34C
H34A—C34—H34C
H34B—C34—H34C
109.5
109.5
109.5
109.5
111.0
109.0
109.40 (13)
C7—C1—C2—C3
C1—C2—C3—C5
C1—C2—C3—C4
C2—C3—C4—O1
C5—C3—C4—O1
C2—C3—C4—O2
C5—C3—C4—O2
C2—C3—C5—C6
C4—C3—C5—C6
C3—C5—C6—C7
C5—C6—C7—C1
C5—C6—C7—C8
C2—C1—C7—C6
C2—C1—C7—C8
C6—C7—C8—C9
C1—C7—C8—C9
C7—C8—C9—C18
C7—C8—C9—C17
0.2 (2)
C15—C16—C17—C9
C18—C9—C17—C16
C8—C9—C17—C16
C10—C9—C17—C16
C8—C9—C18—C19
C17—C9—C18—C19
C10—C9—C18—C19
C8—C9—C18—C26
C17—C9—C18—C26
C10—C9—C18—C26
C26—C18—C19—C20
C9—C18—C19—C20
C18—C19—C20—C21
C18—C19—C20—C25
C25—C20—C21—C22
C19—C20—C21—C22
C20—C21—C22—C23
C21—C22—C23—C24
167.53 (15)
−88.29 (13)
146.44 (11)
27.72 (13)
−44.49 (17)
−171.03 (12)
76.54 (16)
137.40 (13)
10.86 (18)
−101.57 (15)
−1.81 (15)
179.82 (12)
−179.67 (14)
1.36 (16)
1.8 (2)
−175.44 (12)
156.52 (14)
−20.69 (18)
−22.41 (19)
160.38 (13)
−1.6 (2)
175.68 (12)
−0.6 (2)
2.6 (2)
−173.49 (13)
−2.4 (2)
173.66 (13)
−83.83 (17)
100.22 (16)
−64.37 (17)
60.70 (16)
1.6 (2)
−177.31 (14)
−1.1 (2)
−0.4 (3)
Acta Cryst. (2012). C68, o323–o326
sup-6

supplementary materials
C7—C8—C9—C10
175.34 (13)
−155.39 (11)
−33.73 (16)
87.25 (13)
88.37 (13)
−149.97 (12)
−28.99 (14)
−96.36 (13)
20.12 (16)
75.84 (19)
−167.68 (15)
−0.4 (2)
C22—C23—C24—C25
1.3 (2)
C18—C9—C10—O3
C8—C9—C10—O3
C23—C24—C25—C20
C23—C24—C25—C26
C21—C20—C25—C24
C19—C20—C25—C24
C21—C20—C25—C26
C19—C20—C25—C26
C19—C18—C26—C25
C9—C18—C26—C25
C24—C25—C26—C18
C20—C25—C26—C18
C32—C27—C28—C29
C27—C28—C29—C30
C28—C29—C30—C31
C29—C30—C31—C32
C28—C27—C32—C31
C28—C27—C32—C33
C30—C31—C32—C27
C30—C31—C32—C33
C27—C32—C33—N1
C31—C32—C33—N1
C27—C32—C33—C34
C31—C32—C33—C34
−0.9 (2)
177.79 (15)
−0.6 (2)
C17—C9—C10—O3
C18—C9—C10—C11
C8—C9—C10—C11
C17—C9—C10—C11
O3—C10—C11—C16
C9—C10—C11—C16
O3—C10—C11—C12
C9—C10—C11—C12
C16—C11—C12—C13
C10—C11—C12—C13
C11—C12—C13—C14
C12—C13—C14—C15
C13—C14—C15—C16
C12—C11—C16—C15
C10—C11—C16—C15
C12—C11—C16—C17
C10—C11—C16—C17
C14—C15—C16—C11
C14—C15—C16—C17
C11—C16—C17—C9
178.51 (13)
−179.50 (13)
−0.40 (16)
1.56 (15)
179.92 (12)
−179.46 (15)
−0.69 (16)
−1.3 (2)
−171.84 (14)
−0.4 (2)
0.3 (2)
0.7 (3)
0.4 (2)
−0.6 (3)
0.2 (2)
1.3 (2)
1.0 (2)
−177.95 (13)
−0.4 (2)
173.84 (13)
−175.21 (13)
−2.40 (17)
−0.9 (2)
178.92 (14)
−86.92 (17)
93.78 (15)
35.32 (19)
−143.97 (14)
174.50 (15)
−16.65 (15)
Hydrogen-bond geometry (Å, º)
D—H···A
D—H
H···A
D···A
D—H···A
O3—H3A···O2i
N1—H1B···O3ii
N1—H1C···O2iii
N1—H1D···O1
0.85 (2)
0.91 (2)
0.92 (2)
0.91 (2)
1.86 (2)
2.05 (2)
1.88 (2)
1.77 (2)
2.7113 (14)
2.8799 (18)
2.7991 (17)
2.6697 (16)
177 (2)
151 (2)
178 (2)
174 (2)
Symmetry codes: (i) x, y, z−1; (ii) x, y, z+1; (iii) −x+2, y+1/2, −z+2.
Acta Cryst. (2012). C68, o323–o326
sup-7