The crystal structure and conformational studies of acridinedione derivatives

Article abstract of DOI:10.1007/s10870-010-9951-z

Two crystal structures of acridinediones namely, TMHAD and MPHAD were studied by X-ray crystallographic method in view of their occurrence in numerous commercial products including pharmaceuticals, fragrances and dyes. Crystal data of TMHAD are: C₁₇H₂₃NO₂, orthorhombic, Fdd2, with cell parameters a = 40.417(6) A, b = 5.744(1) A, c = 12.979(2) A, V = 3013.1(7) A³, Z = 8, D_cal = 1.205 Mg/m³, μ = 0.078 mm^-1. Crystal data of MPHAD are: C₂₀H₁₈NO₃; monoclinic, P2₁/c with cell parameters a = 10.182(9) A, b = 17.105(14) A, c = 10.895(9) A, β = 117.857(1)°, V = 1678(2) A³, Z = 4, D_cal = 1.268 Mg/m³, μ = 0.085 mm^-1. Both data were collected using λ (MoK_α) = 0.71073 A. The central ring in the acridinedione moieties tends to be planar while the outer two rings adopt sofa conformations. Intermolecular interactions of C-H...O type of hydrogen bond help the molecules to stabilize into the crystal packing. Interestingly, a week forces of C-H...π interactions also helps the molecules for stabilization. Graphical Abstract: Two crystal structures of acridinediones namely, TMHAD and MPHAD have been synthesized and its structural chemistry has been proved by crystallographic study.

Full text of DOI:10.1007/s10870-010-9951-z

J Chem Crystallogr (2011) 41:678–683
DOI 10.1007/s10870-010-9951-z
ORIGINAL PAPER
The Crystal Structure and Conformational Studies
of Acridinedione Derivatives
•
Sampath Natarajan Rita Mathews
Received: 19 May 2010 / Accepted: 30 December 2010 / Published online: 11 January 2011
Ó Springer Science+Business Media, LLC 2011
Abstract Two crystal structures of acridinediones namely,
TMHAD and MPHAD were studied by X-ray crystallo-
graphic method in view of their occurrence in numerous
commercial products including pharmaceuticals, fragrances
and dyes. Crystal data of TMHAD are: C17H23NO2, ortho-
medicinal chemistry field. Also many acridinedione
derivatives have been found as potential laser dyes [1–5]
due to their strong fluorescence properties. So these are
of great potential to be electroluminescence (EL) mate-
rials. In addition, most of these derivatives possess photo
chemical/physical properties [6–8]. Acridinediones having
two keto functional groups at 1st and 8th positions are
found to be good antimalarial agents, and the analogue
compounds are analyzed as potent anti-malarial activity
[10]. Since the acridinedione moiety has the planar
conformation, it is expected to have interaction with
DNA [9].
˚
rhombic, Fdd2, with cell parameters a = 40.417(6) A,
3
˚
˚
˚
b = 5.744(1) A, c = 12.979(2) A, V = 3013.1(7) A ,
Z = 8, Dcal = 1.205 Mg/m3, l = 0.078 mm-1. Crystal
data of MPHAD are: C20H18NO3; monoclinic, P21/c with
˚
˚
cell parameters a = 10.182(9) A, b = 17.105(14) A, c =
3
˚
˚
10.895(9) A, b = 117.857(1)°, V = 1678(2) A , Z = 4,
Dcal = 1.268 Mg/m3, l = 0.085 mm-1. Both data were
collected using k (MoKa) = 0.71073 A. The central ring in
˚
The interactions of acridines with nucleic acids
[11–14] are generally acknowledged to be responsible for
their biological activities. The intercalation hypothesis
[15] suggests that the planar aromatic ring system of the
acridines becomes inserted (intercalated) in between two
adjacent base pairs of a double-stranded nucleic acid. In
addition, accridinediones are used as antibacterial agents
for wound therapy [16] and as antitumour drugs [17].
Substituted hexahydro acridine-1,8-dione, a novel dihy-
dropyridine molecule resembles K-channel openers, which
relaxes KCl precontracted urinary-bladder smooth muscle
in vitro [18, 19]. Apart from the above applications, acrid-
inediones also possess photophysical and electrochemical
properties [20]. Acridinediones act as laser dyes whose
laser activity has been deeply studied by Murugan and
others [4]. In view of the above properties, the crystal
structure determination of two acridinedione compounds
namely, (i) 3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydro-1,8
(2H, 5H) acridinedione (TMHAD) and (ii) 10-(2-methoxy-
phenyl)-3,4,7,9,10-hexahydro-1,8 (2H, 5H) acridinedione
(MPHAD) were carried out by X-ray crystallographic
methods. The chemical diagrams of these molecules are
shown in the Scheme 1.
the acridinedione moieties tends to be planar while the outer
two rings adopt sofa conformations. Intermolecular inter-
actions of C–HÁÁÁO type of hydrogen bond help the molecules
to stabilize into the crystal packing. Interestingly, a week
forces of C–HÁÁÁp interactions also helps the molecules for
stabilization.
Keywords Crystal structure Á Acridinedione Á Pyridine Á
Conformation Á Hydrogen bonding
Introduction
Heterocyclic ring system acridinedione is generally con-
sidered to be one of the most broadly involved rings in
S. Natarajan (&) Á R. Mathews
Department of Advanced Technology Fusion,
Konkuk University, Hwayang-Dong 1, Gwangjin-gu,
Seoul 143-701, Korea
e-mail: sampath@konkuk.ac.kr; sams76@gmail.com
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J Chem Crystallogr (2011) 41:678–683
679
O
O
C
O
Data Collection, Structure Solution and Refinement
O
O
Intensity data were collected on a Siemens SMART CCD
area detector diffractometer [22] with graphite monochro-
A
B
A
B
C
H3
H3
C
CH 3
CH 3
N
C
N
H
˚
mated radiation (k = 0.71073 A). The entire data collec-
CH 3
tion was covered over a hemisphere of reciprocal space by
a combination of three sets of exposures each having a
different / angle (0, 88 and 180°) for the crystal and each
exposure time of 10 s. covered 0.3° in x. The crystal
–to-detector distance was 4 cm and the detector swing
angle was -35°. MPHAD data was collected up to 28.12°
using MoKa and showed 90% data completeness. But a
data collection up to 25° is enough to get the complete
information about the structure using MoKa. MPHAD data
completeness will be increased significantly if the data is
calculated up to 25°. So the 90% of MPHAD data does not
affect the structure quality and is good enough for structure
determination.
D
TMHAD
MPHAD
Scheme 1 Chemical diagram of the molecules of TMHAD and MPHAD
Experimental
Synthesis of Tetraketone
The syntheses of tetraketone compounds 2 and 5 were
achieved according to the procedure described in the literature
[21]. For that purpose, formaldehyde (25 mmol) was added to
the solution of respective cyclohexane-l,3-dione (50 mmol) in
aq. methanol (20 mL) and warmed until the solution became
cloudy. The tetraketone started to separate out. Then, the
reaction mixture was diluted with water to 250 mL and
allowed to stand overnight; the tetraketone was collected by
filtration and dried and recrystallized from methanol.
The structure was solved by direct methods using
SHELXS97 [23] and refined by the program SHELXL97
[24]. The non-hydrogen atoms were refined anisotropically
and the positions of hydrogen atoms were derived from the
difference Fourier map for molecule TMHAD. But for
MPHAD molecule, hydrogen atoms were fixed geometri-
cally and allowed to ride over the model on their parent
atoms. The final cycle of refinement converged to R1 =
0.0672 & 0.1051 and wR2 = 0.1358 & 0.2791, respec-
tively for TMHAD and MPHAD molecules, based on their
observed reflections. The maximum and minimum heights
Preparation of TMHAD
The tetraketones (2, 0.5 mmol) and excess amount of
ammonium acetate (0.7 mmol) were refluxed for 3 h in acetic
acid in presence of catalytic amount of P2O5. The reaction
mixture was cooled and poured into crushed ice. The yel-
low solid obtained TMHAD (3) was filtered, dried and
re-crystallized from MeOH: CHCl3 (1:1) ratio.
in the final difference Fourier map were found to be 0.205
-3
& -0.204 e. A and 0.314 & -0.243 e. A-3, respectively.
Least-squares planes and asymmetry calculations were
done using the program PARST97 [25]. The molecular
graphics were drawn for both molecules using the pro-
grams ORTEP [26], ZORTEP [27] and PLATON [28]. The
crystallographic data and methods of data collection,
solution, and refinement are shown in Table 1. All other
information relevant to these structures TMHAD and
MPHAD are included in the deposited materials (CCDC
771876 & CCDC771875, respectively).
˚
˚
O
O
O
O
O
CH3COONH4
AcOH/ P2O5
HCHO
Aq. MeOH
O
N
H
O
O
1
2
3
Preparation of MPHAD
The tetraketones (5, 0.5 mmol) and excess amount of anisi-
dine (6, 0.7 mmol) were refluxed for 3 h in acetic acid in
presence of catalytic amount of P2O5. The reaction mixture
was cooled and poured into crushed ice. The yellow solid
obtained MPHAD (7) was filtered, dried and re-crystallized
from methanol.
Results and Discussion
The molecule TMHAD shows half molecule symmetry in
the crystal structure and molecule MPHAD shows sin-
gle molecule in the asymmetric unit. The ORTEP and
ZORTEP structures are shown in Fig. 1a and b, respec-
tively with 30% probability of thermal ellipsoid levels.
The central ring (B), namely acridinedione moiety adopts
planar conformation in both molecules, TMHAD and
MPHAD. The fused rings on both sides (A & C) to central
ring of acridinedione moiety show sofa conformations and
H
H
N
O
O
O
O
O
O
O
6
HCHO
N
AcOH/ P2O5
Aq. MeOH
O
O
O
4
5
7
123

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J Chem Crystallogr (2011) 41:678–683
MPHAD
Table 1 Crystal structures data
and relevant parameters
Parameters
TMHAD
CCDC Nos.
CCDC771876
C17H23NO2
273.36
CCDC771875
C20H18NO3
320.35
Empirical formula
Formula weight
Temperature
293(2) K
293(2) K
˚
0.71073 A
˚
0.71073 A
Wavelength
Crystal system, space group
Unit cell dimensions
Orthorombic, Fdd2
Monoclinic, P21/c
˚
a = 40.417(6) A
˚
a = 10.182(9) A
˚
b = 5.744(1) A
˚
b = 17.105(14) A
˚
c = 12.979(2) A
˚
c = 10.895(9) A
–
b = 117.857(1)°
1678(2) A
3
˚
3
˚
Volume
3013.1(7) A
Z, Calculated density
F(000)
8, 1.205 Mg/m3
4, 1.268 Mg/m3
1184
676
Crystal size
0.30 9 0.25 9 0.22 mm
2.02 to 28.33°
-38 B h B 53
-7 B k B 7
-17 B l B 17
4592/1821
0.31 9 0.25 9 0.18 mm
2.26 to 28.12°
-13 B h B 13
-22 B k B 20
-13 B l B 12
9589/3688
Theta range for data collection
Limiting indices
Reflections collected/unique
Absorption correction
None
Full-matrix least-squares on F2
None
Full-matrix least-squares on F2
Refinement method
Data/restraints/parameters
Goodness-of-fit on F2
1821/1/138
3688/0/217
1.068
1.104
Final R indices [I [ 2sigma(I)]
R indices (all data)
R = 0.0672, wR = 0.1358
R = 0.1028, wR = 0.1491
-3
R = 0.1051, wR = 0.2791
R = 0.1900, wR = 0.3223
-3
˚
˚
Largest diff. peak and hole
0.205 and -0.204 e. A
0.314 and -0.243 e. A
atoms C6 (ring A) & C6a (ring B) in molecule TMHAD and
C8 (ring A) & C12 (ring B) in the molecule MPHAD are
deviate from the planarity. Maximum deviation from the
Scheme 2 The possible reso-
nance structure of acridinedione
moiety
_
O
_
O
˚
planarity is -0.304(3) A for atoms C6 & C6a in TMHAD
and atoms C8 & C12 are deviate respectively by -0.242(1)
˚
& 0.257(2) A in MPHAD.
N
H
The central C–N–C angles of both molecules are
123.7(3)° and 121.4(4)°, respectively. These angle values
support sp2 hybridization in both molecules of N1 atom.
The N1–C15 bond distance in the molecule of MPHAD is
˚
C4=] -173.5(2), [C2–C3–C4–O1=] 175.3(3) & [N1–C2–
C3–C8=] 5.0(4)° and for MPHAD [N1–C2–C3–C14=]
178.5(5), [N1–C6–C5–C10=] 176.0(5), [C2–C3–C14–O1=]
174.7(5), [C6–C5–C10–O2=] -174.3(5), [N1–C2–C3–
C4=] -1.5(8) & [N1–C6–C5–C4=] 0.6(8)°. The planarity of
the central ring is further supported by the low value of the
puckering amplitude [32] QT = 0.108(3), when compared
with the values for the other rings A and C of MPHAD for
which QT = 0.239(1) and 0.3706(1), respectively.
1.437(6) A, which is in well agreement with Cphenyl
–
Nacridine bond length of acridinedione structures [17, 18].
˚
The carbonyl group bond lengths [C4–O1=] 1.242(4) A in
˚
TMHAD and [C14–O1=] 1.220(6) A & [C10–O2=]
˚
1.214(7) A in MPHAD are in well agreement with the
values observed for related structures [29–31].
The study of plane calculations, torsion angles, bond
angles and bond lengths prove that the central ring B shows
p-conjugation [O=C–C=C–N–C=C–C=O] which favors
strong aromatic character in both the molecules of acridin-
edione moiety. The possible resonance structure is shown in
Scheme 2. This is also seen from the conformational angles
of the rings in detail as follows: For TMHAD [N1–C2–C3–
In the molecule MPHAD, the planar o-methoxy phenyl
group is bonded with N1 atom to the central ring. This phenyl
ring D is almost perpendicular to the best plane of the central
ring, which is evidenced from the dihedral angle of 87.1(2)°.
Further study of the torsion angles and least-squares planes
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J Chem Crystallogr (2011) 41:678–683
681
Fig. 1 ORTEP diagram of the molecule TMHAD (a) & ZORTEP diagram of the molecule MPHAD (b) showing the thermal ellipsoids at 30%
probability level. The molecule MPHAD hydrogen atoms are removed for clarity
calculation show that the outer rings A and C adopt sofa
conformation. The dihedral angles subtended between the
rings A & B, B & C and A & C are 5.1(2)°, 3.5(2)° & 8.3(2)°,
respectively. The dihedral angle between the rings A and C is
supposed to be called as buckling angle and the degree of
aromaticity is reflected from these low angle values.
The MPHAD structure is reported with larger R1 and
wR2 values due to the higher thermal vibration of some
atoms, namely C8, C9, C12 and C13. This is because of
either one of the reasons that crystal might have diffracted
weakly or might have undergone significant decomposition
during data collection which has led to lower data com-
pleteness too. Higher thermal motions of these anisotropic
ellipsoids of atoms also cast abnormal distances between
the bonds (C8–C9 and C12–C13).
Table 2 Hydrogen bondings and the possible non-bonded interac-
˚
tions (A, °)
D–HÁÁÁA
d (D–H) d (HÁÁÁA) d (DÁÁÁA) [(D–HÁÁÁA)
(a) For molecule TMHADA
C10–H3ÁÁÁO1i
C7–H10ÁÁÁO1ii
N1–H15ÁÁÁO1ii
C5–H8ÁÁÁCg1iii
0.956(1) 2.715(3) 3.480(5) 137.6(3)
0.968(1) 2.585(3) 3.454(4) 149.4(3)
0.736(2) 2.540(2) 3.119(4) 136.9(1)
1.014
2.796
3.800
171.1
(b) For molecule MPHADB
C11–H13AÁÁÁO3i 0.97
0.97
2.870(5) 3.417(8) 116.7(4)
2.921(5) 3.607(9) 128.6(4)
2.928(5) 3.894(8) 173.8(4)
2.872(6) 3.673(9) 140.5(4)
2.638(5) 3.435(8) 144.1(4)
C7–H19BÁÁÁO3i
C4–H10BÁÁÁN1ii
0.97
C12–H21BÁÁÁO2ii 0.97
0.93
C19–H11ÁÁÁO2iii
C4–H10BÁÁÁCg2iv 0.97
2.720
3.330
3.576
3.867
147.4
116.8
C8–H24BÁÁÁCg2v 0.97
Packing Features
A
Equivalent positions: (i) x, y - 1/2, z - 1/2; (ii) x, y ? 1/2,
z - 1/2; (iii) x, 1 ? y, z. Cg1 = N1–C2–C3–C8–C3a–C2
The details of hydrogen bonds for both molecules are given
in Table 2a and b. The C–HÁÁÁO and N–HÁÁÁO types of
intermolecular and C–HÁÁÁO type of intra molecular
hydrogen bonds are playing a major role in crystal packing
in both molecules. The crystal-packing diagrams of mole-
cules TMHAD and MPHAD are given Fig. 2a and b,
respectively. Interestingly, the weak C–HÁÁÁp intermolecu-
lar interactions [33] is also supporting for molecular sta-
bility in the unit cell crystal packing of both molecules. All
the geometrical details of these hydrogen bonds are pre-
sented in the Table 2.
B
Equivalent positions: (i) x, y, z; (ii) -x ? 2, -y, -z ? 2; (iii)
x - 1, -y ? 1/2, z - ‘; (iv) 2 - x, 1 - y, 1 - z; (v) x, 1/2 - y,
-1/2 ? z. Cg2 = N1–C2 through C6. Cg is the centroid of the
benzene rings
Supplementary Material
Crystallographic data (excluding structure factors) for
the structure reported in this article have been depos-
ited with the Cambridge Crystallographic Database Centre
as supplementary publication nos. CCDC771876 and
123

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J Chem Crystallogr (2011) 41:678–683
Fig. 2 Packing of the
molecules TMHAD (a) &
MPHAD (b) viewed down the b
and a-axis, respectively. Dashed
lines represent hydrogen bonds
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